記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: In our aging society, the number of patients with both cancer and dementia has recently been increasing. One of the major clinical questions is whether patients with dementia could receive appropriate cancer treatment. The purpose of this study is to know the prognosis of patients with both cancer and impaired decision-making as a symptom of dementia, and to discuss the proper cancer treatment of the patients with dementia. METHODS: Patients newly diagnosed with both cancer and impaired decision-making as a symptom of dementia at Ehime University Hospital between January 2010 and December 2016 were reviewed. The data of patients with cancer were retrospectively analyzed using an electronic medical record system. RESULTS: In total, 9354 cases were diagnosed with cancer in the Ehime University Hospital over 7 years, and only 105 (1.1%) cases with impaired decision-making as a symptom of dementia were recorded by medical professionals, probably due to poor attention to the cognitive functions of patients with cancer. Analysis of the cancer prognosis of these patients showed that a better prognosis was seen in patients with any therapeutic interventions than in those with no treatment for the cancer itself. However, the prognosis of patients was not significantly different between standard and non-standard treatments. CONCLUSIONS: This study suggests that the poor interest of medical professionals in the cognitive function of patients with cancer at the time of diagnosis of cancer and the lack of any guidelines for patients with both cancer and dementia are major problems in our aging society. Geriatr Gerontol Int 2021; 21: 1105-1110.

DOI： 10.1111/ggi.14292

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) is the standard of care for untreated diffuse large B-cell lymphoma (DLBCL). However, the schedule for rituximab administration has not been optimized. To compare standard R-CHOP with CHOP plus dose-dense weekly rituximab (RW-CHOP) in patients with untreated DLBCL, we conducted a phase 2/3 study (JCOG0601, jRCTs031180139). Patients were randomly assigned to R-CHOP (CHOP-21 with 8 doses of rituximab once every 3 weeks [375 mg/m2]) or RW-CHOP (CHOP-21 with 8 doses of weekly rituximab [375 mg/m2]) groups. The primary end point of the phase 2 component was percent complete response (%CR) of the RW-CHOP arm, whereas that of the phase 3 component was progression-free survival (PFS). Between December 2007 and December 2014, 421 untreated patients were randomly assigned to R-CHOP (213 patients) or RW-CHOP (208 patients). The %CR in the RW-CHOP arm was 85.3% and therefore met the prespecified decision criteria for the phase 2 component. With a median follow-up of 63.4 months, the 3-year PFS and overall survival were 79.2% and 88.7% in the R-CHOP arm and 80.3% and 90.4% in the RW-CHOP arm, respectively. There was no significant difference in PFS (hazard ratio, 0.95; 90.6% confidence interval, 0.68-1.31). Although the safety profile and efficacy of RW-CHOP was comparable with R-CHOP and its tolerability was acceptable, weekly rituximab in combination with CHOP during the early treatment period did not improve PFS in untreated patients with DLBCL. This trial was registered at jrct.niph.go.jp as #jRCTs031180139.

DOI： 10.1182/bloodadvances.2020002567

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pneumocystis jirovecii pneumonia (PJP) is one type of life-threatening pneumonia in immunocompromised patients. PJP development should be considered in not only immunocompromised individuals, but also patients undergoing intensive chemotherapies and immunotherapies, organ transplantation, or corticosteroid treatment. Past studies have described the clinical manifestation of PJP in patients during chemotherapy and reported that PJP affects cancer treatment outcomes. Therefore, PJP could be a potential problem for the management of cancer patients during chemotherapy, and PJP prophylaxis would be important during cancer treatment. This review discusses PJ colonization in outpatients during cancer chemotherapy, as well as in healthy individuals, and provides an update on PJP prophylaxis for cancer patients during chemotherapy.

DOI： 10.3390/pathogens10020237

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The efficiency of upfront consolidation with high-dose chemotherapy/autologous stem-cell transplantation (HDCT/ASCT) for newly diagnosed high-risk diffuse large B-cell lymphoma (DLBCL) may be influenced by induction chemotherapy. To select better induction chemotherapy regimens for HDCT/ASCT, a randomized phase II study was conducted in high-risk DLBCL patients having an age-adjusted International Prognostic Index (aaIPI) score of 2 or 3. As induction chemotherapy, 6 cycles of R-CHOP-14 (arm A) or 3 cycles of R-CHOP-14 followed by 3 cycles of CHASER (arm B) were planned, and patients who responded proceeded to HDCT with LEED and ASCT. The primary endpoint was 2-y progression-free survival (PFS), and the main secondary endpoints included overall survival, overall response rate, and adverse events (AEs). In total, 71 patients were enrolled. With a median follow-up of 40.3 mo, 2-y PFS in arms A and B were 68.6% (95% confidence interval [CI], 50.5%-81.2%) and 66.7% (95% CI: 48.8%-79.5%), respectively. Overall survival at 2 y in arms A and B was 74.3% (95% CI: 56.4%-85.7%) and 83.3% (95% CI: 66.6%-92.1%). Overall response rates were 82.9% in arm A and 69.4% in arm B. During induction chemotherapy, 45.7% and 75.0% of patients in arms A and B, respectively, had grade ≥ 3 non-hematologic toxicities. One patient in arm A and 6 in arm B discontinued induction chemotherapy due to AEs. In conclusion, R-CHOP-14 showed higher 2-y PFS and less toxicity compared with R-CHOP-14/CHASER in patients with high-risk DLBCL, suggesting the former to be a more promising induction regimen for further investigations (UMIN-CTR, UMIN000003823).

DOI： 10.1111/cas.14604

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Screening for total pain and sharing of patient information including adverse events for patients receiving chemotherapy by medical staff is needed in clinical practice. We introduced a sharing system for patient-oriented outcome sheets via a touch panel at an outpatient chemotherapy clinic. This study aimed to assess whether the system contributes to the improved management of treatment-related adverse events. We retrospectively analyzed data from a total of 215 patients at Ehime University Hospital using their electronic medical records from April to August 2015. Forty of these patients had received interventions relating to treatment-related adverse events. The proportion of a total number of interventions before and after the sharing system was 42/282(14.9%)and 45/215(20.9%), respectively. The proportion of a total number of interventions at the first course of outpatient chemotherapy also increased from 9/40(22.5%)to 14/40(35%)compared with before the sharing system. The purpose of interventions were for insomnia, anorexia, and cancer-related pain, etc., listed in order of degree of frequency. These results suggest that a sharing system of patient-reported interview sheets contributes to tracking treatment -related adverse events and aids in ensuring interventions can be efficiently performed by multidisciplinary team members.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Venous pain induced by peripheral intravenous infusion of gemcitabine has remained an unresolved issue in clinical practice. This study aimed to identify differences between gemcitabine formulations as well as risk factors associated with gemcitabine-induced venous pain in patients with cancer. METHODS: We retrospectively analyzed data from consecutive patients with cancer who had received chemotherapy including a lyophilized or liquid formulation of gemcitabine diluted with 5% glucose solution via a peripheral vein. The study was conducted at Ehime University Hospital using electronic medical records dated between January 2015 and July 2017. The primary end point was the prevalence of venous pain at the administration site during gemcitabine infusion, classified as injection site reaction of grade ≥2 according to the Common Terminology Criteria for Adverse Events, version 4.0. A multivariate logistic regression analysis with generalized estimating equations for longitudinal data was used to identify risk factors for venous pain during all courses of gemcitabine treatment. FINDINGS: A total of 1150 treatment courses in 141 Japanese patients were evaluated in this study. Venous pain occurred in 115 courses (10.0%) and in 49 patients (34.8%). The multivariate logistic regression analysis with generalized estimating equations revealed that a dose increase of gemcitabine and use of the liquid formulation of gemcitabine were significantly associated with an increased risk for venous pain (dose increase, adjusted odds ratio [OR] = 1.25; 95% CI, 1.11-1.40 [P < 0.001]; and liquid formulation, adjusted OR = 12.43, 95% CI, 5.61-27.51 [P < 0.001]), whereas age, course number of gemcitabine, and use of the soft-back product of 5% glucose solution were significantly associated with a reduced risk for venous pain (age, adjusted OR = 0.75; 95% CI, 0.57-0.98 [P = 0.037]; course number, adjusted OR = 0.96; 95% CI, 0.92-0.99 [P = 0.023]; and soft back, adjusted OR = 0.39; 95% CI, 0.21-0.74 [P = 0.004]). IMPLICATIONS: The use of the liquid formulation of gemcitabine was associated with a significant increase in the frequency of gemcitabine-induced venous pain despite dilution with 5% glucose solution compared to that with the lyophilized formulation. The lyophilized formulation of gemcitabine should hence be used in peripheral intravenous infusion for the treatment of patients with cancer.

DOI： 10.1016/j.clinthera.2020.02.010

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10147-019-01481-3

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記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.clinthera.2018.10.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-018-34618-x

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記述言語：英語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：英語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although induction immunochemotherapy including high-dose cytarabine and rituximab followed by high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) is recommended for younger patients (≤65 years old) with untreated mantle cell lymphoma (MCL), no standard induction and HDC regimen has been established. We conducted a phase II study of induction immunochemotherapy of R-High-CHOP/CHASER followed by HDC of LEED with ASCT in younger patients with untreated advanced MCL. Eligibility criteria included untreated MCL, stage II bulky to IV, and age 20-65 years. Patients received 1 cycle of R-High-CHOP followed by 3 cycles of CHASER every 3 weeks. Peripheral blood stem cells (PBSC) were harvested during CHASER. LEED with ASCT was delivered to patients who responded to R-High-CHOP/CHASER. Primary endpoint was 2-year progression-free survival (PFS). From June 2008 to June 2012, 45 patients (median age 59 years; range 38-65 years) were enrolled. PBSC were successfully harvested from 36 of 43 patients. Thirty-five patients completed ASCT. Two-year PFS was 77% (80% CI 68-84), which met the primary endpoint. Five-year PFS and overall survival were 52% (95% CI 34-68%) and 71% (95% CI 51-84%), respectively. Overall response and complete response rates after induction immunochemotherapy were 96% and 82%, respectively. The most common grade 4 toxicities were hematological. In younger patients with untreated MCL, R-High-CHOP/CHASER/LEED with ASCT showed high efficacy and acceptable toxicity, and it can now be considered a standard treatment option.

DOI： 10.1111/cas.13719

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(有)科学評論社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier (Singapore) Pte Ltd  

Background: The prognosis of diffuse large B-cell lymphoma (DLBCL) is remarkably improved after R-CHOP therapy. However, there are few detailed reports regarding very elderly DLBCL patients. We investigated relationships between prognostic factors and mortality risk in DLBCL patients, especially those aged 80 years or more. Methods: The study subjects consisted of 141 patients newly-diagnosed with de novo DLBCL. Information regarding age, sex, stage, performance status (PS), lactate dehydrogenase (LDH), extranodal (EN) involvement, and therapies was available. Results: For the 141 patients, the female sex was significantly inversely related to mortality, whereas age ≥80 years, PS ≥2, and non-standard therapy were significantly positively associated with death. No associations were observed between death and stage, LDH, or EN. When classifying patients by age (&lt
80 [n = 108] and ≥80 [n = 33] years), a significant inverse association between female sex and mortality was found only in the latter (very elderly) group. Positive relationships of PS ≥2 with mortality was more pronounced in patients ≥80 years of age than in those &lt
80 years of age. A significant positive relationship with non-standard therapy was found only in patients &lt
80 years of age. Conclusion: PS ≥2 may be positively associated with mortality, regardless of age. Female sex may be inversely related to mortality only in DLBCL patients aged 80 years or more, possibly due to the difference in rituximab clearance between the two study groups.

DOI： 10.1016/j.ijge.2017.11.001

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記述言語：英語   出版者・発行元：(一社)日本リンパ網内系学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Tokyo  

Background: Follicular lymphoma (FL) is the most common type of non-Hodgkin lymphoma (NHL), with indolent progression. Several treatment options are selected, based not only on disease status, quality of life (QOL), and age of patient, but also on recent increasing medical costs. We retrospectively analysed the first-line treatment of FL with regard to treatment outcomes and medical economics, and discuss the appropriate strategies for FL. Methods: Data on a total of 69 newly-diagnosed patients with FL was retrospectively collected from 2001 to 2015. Results: The median age of the patients was 60 years and the median follow-up was 58 months. A total of 25 cases with FL were treated with R monotherapy, and 28 cases were treated with R-CHOP as first-line treatment. The factors affecting the decision of physicians to use R or R-CHOP treatment were serum level of lactate dehydrogenase (LDH) and disease stage. The first-line treatment-associated survival did not show any statistical differences between R and R-CHOP. The average hospitalization and average of all medical costs during the first-line treatment were 4.1 days (R) versus 55.7 days (R-CHOP), and JPY 1,707,693 (USD 15,324) (R) versus JPY 2,136,117 (USD 19,170) (R-CHOP), respectively. Conclusion: R monotherapy for patients whose diseases show low tumor burden and who are not candidates for local treatment has benefits as a first-line treatment compared to R-CHOP, based on the patients’ QOL and medical economics.

DOI： 10.1007/s10147-017-1202-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Background Venous pain induced by peripheral intravenous administration of oxaliplatin remains clinically unresolved. Objective The aim of this study was to determine the efficacy of comprehensive intervention care for venous pain in colorectal cancer patients receiving oxaliplatin. Setting A Japanese tertiary hospital. Method We treated all outpatients after April 2012 with comprehensive intervention care including pre-warming of the oxaliplatin solution, use of a hot compress, and pH adjustment by combination with dexamethasone. We retrospectively reviewed the electronic medical records from colorectal cancer patients who had received oxaliplatin via a peripheral vein between December 2009 and June 2014. Main outcome measures The primary endpoint of this study was the incidence of venous pain at the administration site during oxaliplatin infusion, according to injection site reaction grade ae 2. Results We evaluated 271 treatment courses in 59 patients. Venous pain occurred in 42 courses (15.5%) among 26 patients. Multivariate logistic regression analysis revealed that female gender and body mass index ae 25 kg/m(2) were significantly associated with an increased risk of venous pain during all courses (adjusted odds ratio [OR]: 3.18, 95% confidence interval [CI] 1.35-7.92; P &lt; 0.01; and adjusted OR: 3.37, 95% CI 1.26-9.40; P = 0.02, respectively), whereas comprehensive intervention care were significantly associated with reduced risk of venous pain during all courses (adjusted OR: 0.10, 95% CI 0.02-0.44; P &lt; 0.01). Conclusion Comprehensive intervention care is a clinical treatment option for oxaliplatin-induced peripheral venous pain in patients with colorectal cancer, especially females with obesity.

DOI： 10.1007/s11096-017-0536-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Aims: Pneumocystis Jirovecii (PJ) is regarded as an agent of fungal infection and in cases of pneumocystis pneumonia (PCP) in immune-compromised patients including cancer patients. It is not clear what kinds of cancer, treatments, and environment need prophylaxis for PCP. In this study, we have analyzed the detectability of PJ DNA from sputum, and discussed prophylaxis and risk factors regarding PCP. Methods: A total of forty-nine materials (twenty-four from outpatients during cancer chemotherapies and twenty-five from healthy control subjects) was collected. Their PJ DNAs were amplified using nested PCR with specific primers of the PJ gene (the mitochondrial small subunit rRNA gene). Results: PJ DNA was detectable in 46% of specimens (sputum) from cancer patients during chemotherapies, and incidences of not significantly different among types of cancer and chemotherapy regimens. Prophylactic use of Sulfamethoxazole/Trimetoprim (ST) reduced the detection of PJ DNA. Detection of PJ DNA is not high among healthy non-smokers (20%) and high among healthy smokers (47%). Conclusions: Prophylactic use of ST may be necessary for cancer patients during chemotherapies. Also, smoking may be associated with PJ colonization in the airway and air vesicles, and may increase the mortality rate for PCP. All patients undergoing cancer chemotherapies should cease smoking. (C) 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2017.07.003

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記述言語：日本語   出版者・発行元：愛媛医学会  

【緒言】再発・難治性悪性軟部腫瘍に対する標準治療は確立されていない。近年本邦においては、PALETTE試験の結果から、血管新生阻害作用を持つpazopanibが保険適応となり注目されている。本報告では、愛媛大学医学部附属病院でpazopanibを用いて治療した悪性軟部腫瘍の長期経過と問題点を報告する。【症例】症例は6例(男性3名、女性3名)で平均年齢は65歳(29-81歳)。疾患は平滑筋肉腫3例、悪性線維性組織球腫2例、骨外性軟骨肉腫1例。pazopanib治療前、手術を含め平均1.2レジメンが施行されていた。治療開始後のfollow-upは15.0ヵ月(中央値)、6例中5例が800mg/日、1例が400mg/日で治療開始され、全例において治療は中止された。Grade2(CTCAE v4.0)以上の有害事象としては、食欲不振6例、全身倦怠感6例、肝障害5例、甲状腺機能低下3例、不眠3例、血小板減少2例、下痢1例、高血圧1例、貧血1例。Grade 3の有害事象は血小板減少(1例)、貧血(1例)であった。治療効果は、CR 0例、PR 0例、SD 0例、PD 5例、早期離脱1例で、1例が外来で生存中である。【考察】我々の症例では、推奨用量800mgのpazopanib治療は、倦怠感・食欲不振から継続が困難であり、400mgで開始し増減する事が現実的と考えられた。また、pazopanibの長期内服は原疾患をコントロールする可能性があるものの、治療中のperformance status(PS)の低下は顕著であり、治療前十分な治療説明が必須であると考えられる。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Purpose
As the major toxicity induced by pemetrexed plus carboplatin is severe hematologic toxicities, the aim of this study was to determine the risk factors for severe hematologic toxicities in lung cancer patients.
Methods
We retrospectively investigated data from lung cancer patients who had received pemetrexed plus carboplatin, with or without bevacizumab. This observational study was carried out at Ehime University Hospital using electronic medical records dating from July 2009 to March 2015. Severe hematologic toxicities were defined as grade 3 or 4, according to the Common Terminology Criteria for Adverse Events, version 4.0.
Results
Forty-two patients were included in the study. The incidence of grade 3 or 4 hematologic toxicities during the first cycle of chemotherapy and during all cycles was 19.0% and 16.1%, respectively. Multivariate time-depend generalized estimating equations logistic regression analysis revealed that regular use of non- steroidal anti-inflammatory drugs (NSAIDs) was significantly associated with an increased risk of severe hematologic toxicities during all cycles (adjusted odds ratio (OR): 8.32, 95% confidence interval (CI): 1.27-54.38; p = 0.03), whereas creatinine clearance of &lt;45 mL/min was not significantly associated with an increased risk of severe hematologic toxicities during all cycles (adjusted OR: 0.91, 95% CI: 0.25-3.34; p = 0.88).
Conclusions
The results suggest that severe hematologic toxicities in patients receiving carboplatin-based pemetrexed may be significantly induced by the inhibition of renal tubular pemetrexed secretion through drug-drug interactions between NSAIDs and pemetrexed rather than through glomerular filtration of pemetrexed, even with moderate to sufficient renal function.

DOI： 10.1371/journal.pone.0171066

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IVYSPRING INT PUBL  

Purpose The therapeutic benefit of a three-drug combination of antiemetics has not been established in moderately emetogenic chemotherapy (MEC). The aim of this study was to compare the antiemetic effectiveness and cost-saving of palonosetron plus dexamethasone (control group) with aprepitant, granisetron, and dexamethasone (study group) in cancer patients who received MEC.
Methods We switched the standard antiemetic treatment from the control group to the study group in gastrointestinal cancer patients who received MEC after October 2015. The antiemetics in both groups were modified using salvage antiemetic therapy at the clinicians' discretion, according to the severity of chemotherapy-induced nausea and vomiting. We retrospectively reviewed the electronic medical records from patients, before and after switching groups, from between April 2014 and March 2016.
Results We evaluated 443 treatment courses in 83 patients. The proportion of courses that included salvage antiemetic therapy in the control group and the study group was 34.8 % (116/333) and 8.2 % (9/110), respectively, and was statistically significant (p &lt; 0.001). The mean integrated costs of antiemetics per course in the control group and the study group were 193 +/- 55 USD and 143 +/- 38 USD, respectively. Multivariate logistic regression analysis revealed that the study group was significantly associated with a reduced risk of requiring salvage antiemetic therapy (p = 0.038).
Conclusions These results suggest that the antiemetic effectiveness and cost-saving of a three-drug combination of aprepitant, generic granisetron, and dexamethasone was superior to a two-drug combination of palonosetron plus dexamethasone in gastrointestinal cancer patients who received MEC.

DOI： 10.7150/jca.17102

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(公社)日本整形外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Vancomycin-induced thrombocytopenia is a rare adverse reaction that may be overlooked because no specific diagnostic test is currently available. We herein report a patient with vancomycin-induced immune thrombocytopenia who was diagnosed by the detection of vancomycin-dependent anti-platelet antibody with flow cytometry. An IgG antibody in the patient's serum reacted with platelets only in the presence of vancomycin. Severe thrombocytopenia gave rise to life-threatening gastrointestinal bleeding, which was quickly resolved after effective platelet transfusion following the cessation of vancomycin administration. This report suggests that the flow cytometric test is useful for the differential diagnosis of thrombocytopenia and platelet transfusion should be performed after the cessation of vancomycin administration.

DOI： 10.2169/internalmedicine.55.6902

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

Venous pain induced by oxalipiatin (L-OHP) is a clinical issue related to adherence to the CapeOX regimen. To prevent L-OHP-induced venous pain, we provided nursing care to outpatients who were administered a preheated L-OHP diluted solution using a hot compress. We retrospectively evaluated the risk factors for colorectal cancer patients who had L-OHP-induced phlebitis and venous pain. Furthermore, the preventive effect of nursing care was compared between inpatients and outpatients from January 2010 to March 2012. At the L-OHP administration site, any symptoms were defined as phlebitis, whereas pain was defined as venous pain. A total of 132 treatment courses among 31 patients were evaluated. Multivariate logistic regression analysis revealed that both phlebitis and venous pain were significantly more common in female patients (adjusted odds ratio, 2.357
95%CI: 1.053-5.418
and adjusted odds ratio, 5.754
95%CI: 2.119-18.567, respectively). The prevalence of phlebitis and venous pain did not differ between inpatients and outpatients (phlebitis, 61.3% vs 67.7%
venous pain, 29.0% vs 19.4%). These results suggest that administration of L-OHP via a central venous route should be considered in female patients.

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Background
IgG4-related disease (IgG4-RD) is a new clinical entity of unknown etiology characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. Although aberrancies in acquired immune system functions, including increases in Th2 and Treg cytokines observed in patients with IgG4-RD, its true etiology remains unclear. To investigate the pathogenesis of IgG4-RD, this study compared the expression of genes related to innate immunity in patients with IgG4-RD and healthy controls.
Materials and Methods
Peripheral blood mononuclear cells (PBMCs) were obtained from patients with IgG4-RD before and after steroid therapy and from healthy controls. Total RNA was extracted and DNA microarray analysis was performed in two IgG4-RD patients to screen for genes showing changes in expression. Candidate genes were validated by real-time RT-PCR in 27 patients with IgG4-RD and 13 healthy controls.
Results
DNA microarray analysis identified 21 genes that showed a greater than 3-fold difference in expression between IgG4-RD patients and healthy controls and 30 genes that showed a greater than 3-fold change in IgG4-RD patients following steroid therapy. Candidate genes related to innate immunity, including those encoding Charcot-Leyden crystal protein (CLC), membrane-spanning 4-domain subfamily A member 3 (MS4A3), defensin alpha (DEFA) 3 and 4, and interleukin-8 receptors (IL8R), were validated by real-time RT-PCR. Expression of all genes was significantly lower in IgG4-RD patients than in healthy controls. Steroid therapy significantly increased the expression of DEFA3, DEFA4 and MS4A3, but had no effect on the expression of CLC, IL8RA and IL8RB.
Conclusions
The expression of genes related to allergy or innate immunity, including CLC, MS4A3, DEFA3, DEFA4, IL8RA and IL8RB, was lower in PBMCs from patients with IgG4-RD than from healthy controls. Although there is the limitation in the number of patients applied in DNA microarray, impaired expression of genes related to innate immunity may be involved in the pathogenesis of IgG4-RD as well as in abnormalities of acquired immunity.

DOI： 10.1371/journal.pone.0126582

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Background: Central nervous system (CNS) relapse is an uncommon but challenging complication in patients with mantle cell lymphoma (MCL). Survival after CNS relapse is extremely poor. Identification of high-risk populations is therefore critical in determining patients who might be candidates for a prophylactic approach.
Patients and methods: A total of 608 patients (median age, 67 years; range 22-92) with MCL newly diagnosed between 1994 and 2012 were evaluated. Pretreatment characteristics and treatment regimens were evaluated for their association with CNS relapse by competing risk regression analysis.
Results: None of the patients received intrathecal prophylaxis. Overall, 33 patients (5.4%) experienced CNS relapse during a median follow-up of 42.7 months. Median time from diagnosis to CNS relapse was 20.3 months (range: 2.2-141.3 months). Three-year cumulative incidence of CNS relapse was 5.6% [95% confidence interval (95% CI) 3.7% to 8.0%]. Univariate analysis revealed several risk factors including blastoid variant, leukemic presentation, high-risk MCL International Prognostic Index and high Ki-67 (proliferation marker). Multivariate analyses revealed that Ki-67 &gt;= 30 was the only significant risk factor for CNS relapse (hazard ratio: 6.0, 95% CI 1.9-19.4, P = 0.003). Two-year cumulative incidence of CNS relapse in patients with Ki-67 = 30 was 25.4% (95% CI 13.5-39.1), while that in the patients with Ki-67 &lt; 30 was 1.6% (95% CI 0.4-4.2). None of the treatment modalities, including rituximab, high-dose cytarabine, high-dose methotrexate or consolidative autologous stem-cell transplant, were associated with a lower incidence of CNS relapse. Survival after CNS relapse was poor, with median survival time of 8.3 months. There was no significant difference in the survival by the site of CNS involvement.

DOI： 10.1093/annonc/mdv074

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

DOI： 10.1007/s00277-014-2052-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Background Febrile neutropenia (FN) is one of the serious complications of chemotherapy. However, the hematological nadir after chemotherapy and the timing of prophylaxis for FN remain unclear, especially for outpatients.
Methods We prospectively analyzed laboratory data from outpatients treated with a single chemotherapy regimen, rituximab (R)-CHOP, on three consultation days (days 8, 10, and 15) after chemotherapy to identify any factors that might predict the onset of the hematological nadir and the optimal timing of G-CSF prophylaxis.
Results A total of 100 courses of chemotherapy (total 33 patients) were analyzed. Onset of the hematological nadir was not predictable in any of the patients who had a white blood cell count (WBC) of &gt;5,500 x 10(6)/L and/or monocyte count of &gt;80 x 10(6)/L on day 8, and thus there was little opportunity for G-CSF prophylaxis in each treatment course. Among patients who had a WBC count of 1,500-5,500 x 10(6)/L on day 8, the monocyte count on day 8 was significantly associated with the hematological nadir. Patients who had a monocyte count of &lt;5 x 10(6)/L on day 8, were identified as a high-risk group for neutropenia for whom G-CSF administration during the current treatment course should be considered.
Conclusion Our results indicate that, in outpatients receiving R-CHOP chemotherapy, the monocyte count on day 8 is a useful marker of the hematological nadir, allowing an opportunity for G-CSF prophylaxis.

DOI： 10.1007/s10147-013-0523-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

DOI： 10.1007/s00428-013-1514-1

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

The "Cancer Chemotherapy and its Management" subcommittee at the Ehime Cancer Care Network Priority Hospitals (Ehime Cancer Kyoten Hospitals) with a focus on medical expenses associated with chemotherapy, surveyed awareness among 98 clinicians regarding certifications of eligibility for Limited Health Insurance Payments during cancer treatment. This committee also lists social and clinical problems encountered at the Ehime Cancer Care Network Priority Hospitals. In our survey, 78% of clinicians were consulted about medical expenses associated with chemotherapy and were actively involved in resolving medical expense problems and resulting correspondences. However, only 38% of clinicians could explain the details of the Japanese guideline on the catastrophic cap and the certifications of eligibility for Limited Health Insurance Payments. This knowledge deficit was more pronounced in younger residents. From our analyses of the awareness about medical expenses among clinicians, we recommend the establishment of the following systems for the management of cancer patients. First, establish a reporting system and early consultation on the catastrophic cap and the certifications of eligibility before initiating cancer treatment. Second, education regarding medical expenses should be mandatory for clinicians, especially for young residents. Third, patients with cancer suffering in the interval of the medical expense and the social system should be relieved with new systems.

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Venous pain induced by oxaliplatin (L-OHP) is a clinical problem in relation to adherence in the CapeOX regimen. We investigated the preventive effect of nursing care preheating administration of L-OHP a hot compress for colorectal cancer patients who received L-OHP via the peripheral venous route between January 2010 and January 2011. L-OHP was diluted in 500 mL of 5% glucose and administered by 2 hours. We evaluated a total of 64 courses among fifteen patients. The presence of any symptoms, any pain with or without touch, and some symptoms of numbness at the L-OHP-administered arm were defined as phlebitis, venous pain, and acute peripheral neuropathy, respectively. The prevalence of phlebitis, venous pain, and acute peripheral neuropathy in the nursing care group was 56.5%, 32.6%, and 25.8%, respectively, which was not significantly less in comparison with the control group (72.2%, 38.9%, and 54.5%, respectively). These results suggest that both types of nursing care, preheating administration and a hot compress, may be effective for the relief of acute peripheral neuropathy induced by L-OHP.

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BENTHAM SCIENCE PUBL LTD  

R (rituximab)-CHOP (cyclophosphamide, adriamycin, vincristin, and prednisone) is given to outpatients with CD20-positive lymphoma as a standard treatment. However, this regimen requires long-term infusion because of the necessity for monitoring the infusion reaction (IR) during R administration. In this study, pharmacological changes in anti-tumor agents were examined after the joint use of R and CHOP, and the possibility of concurrent administration of R and CHOP for outpatients was discussed. After combining antitumor agents with R, the binding capacity of R to the CD20 peptide and molecular changes in anti-tumor agents were measured by ELISA and LC/MS/MS-based analysis. At the same time, a pilot study involving concurrent administration of R and CHOP to patients with diffuse large B-cell lymphoma (DLBCL) was carried out after the first course of R-CHOP. After combining with either adriamycin or cyclophosphamide, the binding capacity of R to the CD20 antigen was equivalent to controls, and no molecular changes in adriamycin and cyclophosphamide were detected after combination with R. Twenty-one cases of DLBCL were treated safely with concurrent administration of R and CHOP. Twenty patients achieved complete remission after a full course of R-CHOP. The results indicated that long-term medication might not be necessary for outpatients treated with R-CHOP.

DOI： 10.2174/187152012802650138

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記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Activation-induced cytidine deaminase (AID/AICDA) is required for somatic hypermutation and class-switch recombination of the immunoglobulin gene, and for c-myc translocation of germinal center-derived B-cell lymphoma. In the present study, we attempted to clarify the significance of AID associated with c-myc in the progression of follicular lymphoma (FL) using RT-PCR and quantitative real-time PCR. Tissues from the patients with grade 3 FL expressed relatively higher levels of c-myc and AID. The samples taken from a patient with FL who died within 2 years after the start of treatment showed either no or low expression of AID, despite expressing high levels of c-myc. In order to examine the role of AID expression in rapidly progressive FL, the full-length AID transcript was transfected into AID-negative cell lines established from different patients with rapidly progressive FL. This led to the establishment of AID-expressing transfectants with a low proliferation rate and a significantly increased incidence of G0/G1 arrest compared with controls. Our results indicate that AID may act as a negative regulator of cell survival in FL when sufficient c-myc is expressed. Switch-off or low expression of AID after c-myc amplification may correlate with the clinical outcomes of FL. (Cancer Sci 2012; 103: 415421)

DOI： 10.1111/j.1349-7006.2011.02186.x

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：英語   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

In order to analyze the clinical activity and cost-effectiveness of granulocyte colony-stimulating factors (G-CSF), the prophylactic usage of G-CSF in patients treated with a single chemotherapy regimen during early courses was prospectively evaluated.
Thirty patients with newly diagnosed non-Hodgkin lymphoma (NHL) treated with the first course of an R-CHOP regimen were enrolled randomly. After treatment with the first course of chemotherapy, a daily dose of G-CSF (lenograstim, 100 mu g) was administered to half (15 cases) of the patients, and a dose of G-CSF (100 mu g) was administered every other day to the other half of the patients when leukocytopenia (&lt; 1.5 x 10(9)/L) and/or neutropenia (&lt; 0.5 x 10(9)/L) occurred. Changes in leukocyte and neutrophil counts, prophylaxis, febrile neutropenia (FN) events, and cost performance between the two groups were analyzed.
No significant difference between the two groups was observed in recoveries of leukocyte and neutrophil counts and evidence of FN. The only difference was the total cost of G-CSF.
We concluded that every-other-day use of G-CSF was as clinically effective for the prophylaxis of FN as the daily use of G-CSF, and economically speaking, the administration of G-CSF every other day should be more beneficial for patients with NHL during early courses of R-CHOP chemotherapy.

DOI： 10.1007/s10147-010-0134-x

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

Ehime Priority Hospitals of Cancer Care Network (Ehime Cancer Kyoten Hospitals) regularly have meetings to discus the current problems in cancer care in Ehime Prefecture. We established three subcommittees: "Registration of Cancer Incident," "Critical Paths for the Management of Patients with Cancer," and "Palliative Care for Patients with Advanced Cancer" to exchange our opinions. We recently set up a new subcommittee related to the physical and spiritual care of patients undergoing chemotherapy treatment, "A Subcommittee dealing with Cancer Chemotherapy and its Management". "This subcommittee has tried to identify current problems with chemotherapy for outpatients in each institution through questionnaire and analysis. As a result of this survey, it was found that Ehime Priority Hospitals have total of seventy-three beds for outpatients undergoing chemotherapy, and that they performed chemotherapy 19, 671 times in 2008. A total of eight oncology physicians and sixteen oncology nurses were engaged in performing chemotherapy in this system. The questions patients most frequently asked during chemotherapy concerned the management of therapy-related complications, dealing with problems at night and during holidays after chemotherapy, and financial problems related to the costs of treatment. In this study we found three issues that need to be managed in Ehime Priority Hospitals. First, for the nursing of outpatients undergoing chemotherapy, more staff engaged in different types of care is required. Second, a new system to deal with emergencies at night and during holidays after chemotherapy is necessary, because Ehime Priority Hospitals use the same system to deal with chemotherapy patients as for other patients. Third, cooperation between pharmacies and out-clinics is important for patient compliance during chemotherapy, especially for the administration of oral anti-tumor agents. Ehime Priority Hospitals of Cancer Care Network is trying to improve each institution while dealing with these problems.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INFORMA HEALTHCARE  

Recent clinical trials have demonstrated that cilostazol, an antiplatelet drug competent to inhibit phosphodiesterase 3, is effective in secondary prevention of atherothrombosis including ischemic stroke, myocardial infarction, and peripheral arterial disease. However, there is no reliable assay for detection of the platelet response to cilostazol. We attempted to establish such an assay for clinical use. Phosphorylation of vasodilator-stimulated phosphoprotein (VASP) subsequent to the pharmacological action of cilostazol was measured by a platelet VASP assay kit that has been widely used for monitoring platelet response to ADP receptor antagonists in clinical settings. We modified the kit and found the optimal conditions for detection of cilostazol-dependent VASP phosphorylation. The assay could detect the in vitro and in vivo platelet responses to cilostazol effectively in the presence of 50 nM PGE1. ROC analysis showed that our assay had 97%% sensitivity and 75%% specificity when blood drawn between 3 and 9 h after cilostazol ingestion was subjected to the assay. The assay results were verified by immunoblotting specific for VASP phosphorylation. Standard light transmission platelet aggregometry could not detect significant inhibition of agonist-induced platelet aggregation by cilostazol except for the in vitro effect of high concentrations of cilostazol. These results demonstrate that the platelet VASP assay can detect the platelet response to cilostazol with high sensitivity and specificity.&lt;/.

DOI： 10.3109/09537104.2010.525976

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Only a few reports have described regression of rectal mucosa-associated lymphoid tissue (MALT) lymphoma after antibiotic treatment are generally found to be successful for gastric tumors. We examined eight rectal MALT lymphomas treated with antibiotic treatments to determine whether they regressed after treatment. We also discuss the relationship between rectal MALT lymphomas and MALT1 gene genetic abnormalities. Eight patients who had undergone antibiotic treatments were followed up with colonoscopy after initiation of the treatment. In five of the eight cases (63%) endoscopic examination showed that the rectal tumor had disappeared, which was confirmed histologically. Polymerase chain reaction for immunoglobulin heavy chain identified a monoclonal band in seven of eight cases (88%). Of the eight cases analyzed with fluorescence in situ hybridization (FISH) for MALT1 translocation, two demonstrated MALT1 gene genetic abnormality. These cases tended to be resistant to antibiotic treatment. Investigation and analysis of a large number of rectal MALT lymphomas are needed to establish suitable standards for antibiotic treatment.

DOI： 10.1111/j.1440-1827.2010.02538.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

This study reports the association of the chromosomal abnormality derivative (1;18)(q10;q10) with essential thrombocythemia (ET) occurring in a 75-year-old woman. Allele-specific polymerase chain reaction also revealed a V617F mutation in the Janus Kinase 2 gene (JAK2) in the platelet compartment in this patient. The der(1;18)(q10;q10) abnormality has previously been reported in two cases of myeloid disorders. The etiological implications for ET of this combination of chromosomal abnormality and JAK2 mutation still remain elusive. This is a novel report of derivative (1;18)(q10;q10) abnormality in ET. (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cancergencyto.2010.02.001

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Nova Science Publishers, Inc.  

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

DOI： 10.1007/s12185-009-0430-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：FERRATA STORTI FOUNDATION  

Background
Lymphoid neoplasm with 18q21.3/BCL2 and 8q24/MYC translocation to immunoglobulin (IG) genes as dual-hit lymphoma/leukemia is very rare and known to have a poor clinical outcome.
Design and Methods
To clarify the clinicopathological characteristics of this malignancy, we analyzed 27 cases of cytogenetically proven dual-hit lymphoma/leukemia.
Results
Dual-hit lymphoma/leukemia was diagnosed at presentation in 22 cases and at relapse or disease progression in 5 cases. At the time of diagnosis of dual-hit lymphoma/leukemia, extranodal involvement was found in 25 cases (93%) and central nervous system involvement occurred in 15 cases (56%). The median survival and 1-year survival rate of the 27 cases were only 6 months and 22%, respectively, after diagnosis of the dual-hit lymphoma/leukemia. Seven cases of triple-hit lymphoma/leukemia (dual-hit lymphoma/leukemia with 3q27/BCL6 translocation) were included; the median survival of these patients was only 4 months from the diagnosis of the dual-hit lymphoma/leukemia. The duration of survival of the patients with a triple-hit malignancy was shorter than that of the other 20 cases of dual-hit lymphoma/leukemia (p=0.02). The translocation partner of MYC subdivided the dual-hit cases into two groups; 14 cases of IGH and 13 cases of IGK/L The MIB-1 index was investigated in 14 cases with aggressive B-cell lymphoma, and was higher in the group with MYC-IGH translocation (n=7) than in the MYC-IGK/L group (n=7) (p=0.02). Overall survival was not different between the MYC-IGK/L translocation group (n=14) and the MYC-IGK or MYC-IGL translocation group (n=13).
Conclusions
Dual-hit lymphoma/leukemia is a rare but distinct mature B-cell neoplasm with an extremely poor prognosis characterized by frequent extranodal involvement and central nervous system progression with either of the translocation partners of MYC.

DOI： 10.3324/haematol.2008.005355

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

DOI： 10.1111/j.1365-2141.2009.07695.x

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

We previously reported that the prognosis of CD21-positive diffuse large B-cell lymphoma (DLBCL) is significantly favorable to that of CD21-negative DLBCL (Otsuka et al. in Br J Haematol 127:416-424, 2004). In this study, we attempted to clarify the biological significance of CD21 expression in B-cell lymphoma (BCL) by performing in vitro experiments using CD21 transfection into a CD21-negative lymphoma cell line and analyzing clinical data from lymphoma samples. Established clones of CD21 transfectants showed homotypic aggregation in suspension culture. Analysis of integrin expression revealed that LFA-1 appeared to be expressed on CD21 transfectants, and the cell aggregation was abrogated by anti-LFA-1 antibody. The CD21 transfectants could adhere to plastic plates coated with ICAM-1. Moreover, flow cytometry and/or immunohistochemical analyses of clinical BCL samples (n = 29) revealed positive for CD21 in all cases; LFA-1 was also expressed without exception. All BCL cells isolated from cavity fluids (n = 10) failed to express both CD21 and LFA-1. These data suggest that CD21 is tightly related to LFA-1 expression in BCL and the absence of CD21/LFA-1 expression is associated with pleural/peritoneal fluid involvement by BCL, a potential indicator of disease progression of BCL.

DOI： 10.1007/s12185-009-0303-8

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：日本語   出版者・発行元：一般社団法人 日本血液学会  

症例は66歳，女性。2007年5月，右鎖骨部腫瘤が出現。6月，腫瘤が増大したため入院した。同部位より生検を施行し，CD20陽性diffuse large B cell lymphomaの診断が得られた。病期診断のために行ったGaシンチグラフィーで右鎖骨，右大腿骨，右膝関節，右足関節，左下腿に異常集積が認められた。しかし，単純X線及びCTでは明らかな異常所見を認めなかった。一方，MRIでは右大腿骨にT1強調画像で低信号域，T2強調画像で低信号域の中に一部高信号域を示し，同部位にも病変があることが示唆された。CHOP療法を開始し，速やかに鎖骨部腫瘤は縮小した。開始後7日目にリツキシマブを投与した。その深夜，トイレから立ち上がった際に左脛骨，腓骨遠位部および右大腿骨転子部を骨折した。両部位ともにGaシンチグラフィーで異常集積があり，病的骨折が考えられた。骨原発悪性リンパ腫は稀な疾患であり，その治療中に病的骨折をおこすという特異な経過であり，報告する。

DOI： 10.11406/rinketsu.50.187

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その他リンク： http://search.jamas.or.jp/link/ui/2009352342

記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

ZNF521 (zinc finger protein 521) is a transcription factor with an N-terminal transcriptional repressor motif and 30 zinc finger domains. Although a high expression level of ZNF521 in human CD34(+) progenitors and hematopoietic malignancies has been demonstrated, the functional role of ZNF521 in hematopoietic cell differentiation has not been clarified. In this study, we analyzed the role of ZNF521 in erythroid cell differentiation using the short hairpin RNA (shRNA)-mediated gene silencing method. Down-regulation of ZNF521 mediated by transient expression of shRNA for ZNF521 resulted in increased synthesis of hemoglobin in K562 and HEL cell lines as compared with control cells. K562-derived clones in which ZNF521 was constitutively silenced by shRNA also showed marked synthesis of hemoglobin and an increased expression level of glycophorin A. Since GATA-1 is the key regulator of erythroid differentiation, the effect of ZNF521 on transcription activity of GATA-1 was analyzed using a luciferase assay. GATA-1 activity was markedly inhibited by ZNF521 in a dose-dependent manner. Deletion analysis of ZNF521 showed that the repressive effect requires an N-terminal repression motif. Furthermore, the direct interaction of ZNF521 with GATA-1 was demonstrated. These results indicate that ZNF521 modulates erythroid cell differentiation through direct binding with GATA-1.

DOI： 10.1074/jbc.M805874200

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC HEMATOLOGY  

Aurora-A kinase (Aur-A) is a member of the serine/threonine kinase family that regulates the cell division process, and has recently been implicated in tumorigenesis. In this study, we identified an antigenic 9-amino-acid epitope (Aur-A(207-215): YLILEYAPL) derived from Aur-A capable of generating leukemia-reactive cytotoxic T lymphocytes (CTLs) in the context of HLA-A*0201. The synthetic peptide of this epitope appeared to be capable of binding to HLA-A*2402 as well as HLA-A*0201 molecules. Leukemia cell lines and freshly isolated leukemia cells, particularly chronic myelogenous leukemia (CML) cells, appeared to express Aur-A abundantly. Aur-A-specific CTLs were able to lyse human leukemia cell lines and freshly isolated leukemia cells, but not normal cells, in an HLA-A*0201 restricted manner. Importantly, Aur-A specific CTLs were able to lyse CD34(+) CML progenitor cells but did not show any cytotoxicity against normal CD34(+) hematopoietic stem cells. The tetramer assay revealed that the Aur-A(207-215) epitope-specific CTL precursors are present in peripheral blood of HLA-A*0201-positive and HLA-A*2402 positive patients with leukemia, but not in healthy individuals. Our results indicate that cellular immunotherapy targeting Aur-A is a promising strategy for treatment of leukemia. (Blood. 2009; 113: 66-74)

DOI： 10.1182/blood-2008-06-164889

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Patients with acquired immune deficiency syndrome (AIDS) are susceptible to secondary malignant tumors. Among those malignancies, the increased incidence of germ cell tumor (GCT) in patients with AIDS has recently been documented in Western countries, while that is still rare in Japan. Here, we report a man patient with advanced GCT (seminoma) complicated with AIDS who was continuously treated with highly active antiretroviral therapy (HAART). A partial response was obtained after resection of the primary left testis and three courses of chemotherapy. During the clinical course, he contracted unexpected gastric bleeding that made it impossible to take HAART agents and prophylactic agents for opportunistic infection. Thereafter, he suffered from a severe pulmonary infection and consequently died of severe respiratory failure. The lymphopenia related to both chemotherapy and AIDS synergistically rendered this patient immunoincompetent and thus he suffered from this fatal pulmonary infection. The recent progress in AIDS treatment has been reported to prolong the survival of tumor-bearing AIDS patients, especially GCT-bearing AIDS patients. Because of the current increase in the number of AIDS patients in Japan, it is important to report the present case which indicated that careful chemotherapy against GCT with strict management of the immunoincompetence can provide a good prognosis for GCT-bearing AIDS patients.

DOI： 10.2169/internalmedicine.48.2357

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：英語   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

CML66 is a newly identified differentiation antigen that is expressed broadly in human leukemia and solid tumors, but its physiological function remains unknown. In the present study, to clarify the feasibility of CML66-targeted cancer immunotherapy, we attempted to identify cytotoxic T lymphocyte (CTL) epitopes derived from CML66. An immunogenic CML66-derived epitope (amino acid residues 76 - 84; YYIDTLGRI) capable of inducing human leukocyte antigen (HLA)-A*2402-restricted CTL specific for this peptide was identified. CML66-derived peptide-specific CTL efficiently lysed human leukemia cells, but not normal cells, in a HLA-A*2402-restricted fashion. Quantitative real-time polymerase chain reaction revealed that CML66 mRNA is expressed abundantly in primary acute myeloid leukemia cells, acute lymphoid leukemia cells, and chronic myelogenous leukemia cells in advanced phase, and that the expression level of CML66 mRNA in normal cells is low compared with that in leukemia cells. CML66-specific CTL precursors were detected in the peripheral blood of patients with acute leukemia. These data indicate that the CML66-derived epitope identified in the present study is a new target antigen for cellular immunotherapy of human leukemia.

DOI： 10.1111/j.1349-7006.2008.00823.x

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記述言語：日本語   出版者・発行元：(一社)日本リンパ網内系学会  

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Integrin cytoplasmic tails regulate integrin activation that is required for high affinity binding with ligands. The interaction of the integrin beta subunit tail with a cytoplasmic protein, talin, largely contributes to integrin activation. Here we report the cooperative interaction of the beta 3 membrane-proximal and -distal residues in regulation of talin-mediated alpha IIb beta 3 activation. Because a chimeric integrin, alpha IIb beta 3/beta 1, in which the beta 3 tail was replaced with the beta 1 tail was constitutively active, we searched for the residues responsible for integrin activation among the residues that differed between the beta 3 and beta 1 tails. Single amino acid substitutions of Ile-719 and Glu-749 in the beta 3 membraneproximal and -distal regions, respectively, with the corresponding beta 1 residues or alanine rendered alpha IIb beta 3 constitutively active. The I719M/E749S double mutant had the same ligand binding activity as alpha IIb beta 3/beta 1. These beta 3 mutations also induced alpha V beta 3 activation. Conversely, substitution of Met-719 or Ser-749 in the beta 1 tail with the corresponding beta 3 tail residue (M7191 or S749E) inhibited alpha IIb beta 3/beta 1 activation, and the M719I/S749E double mutant inhibited ligand binding to a level comparable with that of the wild-type alpha IIb beta 3. Knock down of talin by short hairpin RNA inhibited the I719M- and E749S-induced alpha IIb beta 3 activation. These results suggest that the beta 3 membraneproximal and -distal residues cooperatively regulate talin-mediated alpha IIb beta 3 activation.

DOI： 10.1074/jbc.M707246200

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記述言語：日本語   出版者・発行元：The Japanese Society of Internal Medicine  

血管内大細胞型B細胞性リンパ腫（intravascular large B-cell lymphoma；ILV）は全身の小·中血管内を増殖の場とする特異な悪性リンパ腫である．症例は47歳女性．全身倦怠感を主訴に受診．胸部CTで両肺野にびまん性にごく淡いスリガラス影を認め過敏性肺臓炎が疑われたが，気管支鏡下肺生検によりB細胞性リンパ腫と診断．rituximab併用化学療法（R-CHOP療法）施行し経過良好である．<br>

DOI： 10.2169/naika.96.2783

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その他リンク： https://jlc.jst.go.jp/DN/JALC/00304871122?from=CiNii

記述言語：英語   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CARDEN JENNINGS PUBL CO LTD  

Ocular adnexal extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (ocular adnexal MALT lymphoma) are predominately low-grade, small B-cell types and may be caused by several Putative inflammatory agents. Twenty-three ocular adnexal MALT lymphoma cases, the monoclonality of which was confirmed by examination of immunoglobulin heavy chain gene rearrangement and/or cell surface antigens, were analyzed for evidence of several causative factors. A serologic evaluation of our series of patients showed no evidence of infection by Epstein-Barr virus, hepatitis C virus, or Chlamydophila psittaci. Two patients tested positive for serum antibodies for autoimmunity, and another 2 patients tested positive for antibodies against Chlamydia trachomatis. Polymerase chain reaction analysis did not reveal the presence of the chlamydial 16S ribosomal RNA (rRNA) gene or the 16S-23S spacer rRNA gene. These results indicate that the inflammatory agents in our series of ocular adnexal MALT lymphomas are still unknown and that some types of chlamydial infections are not associated with orbital adnexal MALT lymphoma in southern regions of Japan.

DOI： 10.1532/IJH97.06065

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記述言語：英語   出版者・発行元：MARY ANN LIEBERT INC  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

A 70-year-old Japanese man presented to our hospital with a 1-month history of progressive general fatigue and anorexia. A physical examination revealed severe anemic condition, mild persistent splenomegaly, and no palpable surface lymph nodes. He had pleural effusion and ascites, though no malignant cells were detected in the effusion. He eventually died without any diagnosis of his disease. Immunohistochemical staining of his tumor after autopsy showed atypical cells that were negative for epithelial membrane antigen (EMA), keratin (AE1/3), keratin-20, vimentin, factor VIII, leukocyte common antigen (LCA/T200; CD45), myeloperoxidase (MPO), terminal deoxynucleotidyl tranferase (TdT), lysozyme, CD1a, CD3, CD4, CD10, CD15, CD20 (L26), CD21, CD23, CD34, CD43, CD56, CD68, CD79a, CD138, and EBER-1 in situ. Only a few scattered cells expressed CD30, but they showed no staining for anaplastic large-cell lymphoma kinase (ALK). A few scattered cells expressed S-100 antigen and the majority of cells dominantly expressed dendritic cell-associated antigens (CD35, FDC, Ki-M1p). In conclusion, we found this unknown primary tumor to be consistent with a follicular dendritic cell tumor with anaplastic features.

DOI： 10.1007/s10147-006-0626-x

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記述言語：英語   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：日本語   出版者・発行元：日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：日本語   出版者・発行元：(一社)日本リンパ網内系学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Objective. Monocyte-derived dendritic cells (DCs) play important roles in the immune response against infections and malignancies. Human herpesvirus 6 (HHV-6) infects monocytes and is reactivated in immunodeficient patients. To clarify the mechanisms of HHV-6-induced immunodeficiency, we investigated the effect of HHV-6 infection on differentiation of monocytes to DCs.
Methods. Monocytes were inoculated with or without HHV-6 and then allowed to differentiate to myeloid DCs in culture medium containing granulocyte-macrophage colony-stimulating factor and interleukin (IL)-4. The expression of cell surface molecules on DCs and the capacity of the DCs for antigen capture were examined by flow cytometric analysis. Alteration of antigen-presenting capacity induced by HHV-6 infection was examined.
Results. The morphology of HHV-6-infected monocyte-derived DCs was distinctly different from that of the DCs derived from mock-infected monocytes. Although expression levels of DC-associated surface antigens, including CD80, CD83, and CD86, were significantly higher on HHV-6-infected monocyte-derived DCs than on DCs derived from mock-infected monocytes, antigen-presenting capacity was significantly lower in the former group. Addition of culture supernatant of HHV-6-infected monocytes resulted in suppression of the T-lymphocyte proliferative response, and anti-IL-10 neutralizing antibody partly inhibited this suppressive effect. The antigen-presenting capacity of DCs generated from a patient with severe HHV-6 reactivation was significantly lower than that of DCs generated from the same patient in the recovery phase.
Conclusions. HHV-6 infection induces immunodeficiency via impaired differentiation of DCs. These results present a new concept for the pathogenesis of HHV-6-induced immunodeficiency. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc.

DOI： 10.1016/j.exphem.2006.02.001

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japan Geriatrics Society  

A 75-year-old woman was given a diagnosis of malignant lymphoma (non-Hodgkin, diffuse large B cell type, stage IIA) at our hospital on August 2003. She received six courses of rituximab-based chemotherapy (R-CHOP regimen) and then she achieved complete remission. On August 16, 2004, she was readmitted in our hospital for difficulty in swallowing. Upper gastrointestinal endoscopy reveled esophageal stricture and an ulcerative lesion on the esophageal mucosa. The X-ray examination of the upper gastrointestinal tract reveled a severe esophageal stricture with niches and hiatus hernia. No malignancy was seen on CT scanning, gallium radioisotope scanning and histological examination of biopsy specimens with the upper gastrointestinal endoscopy. The physical examination showed gibbosity, and MR imaging showed multiple compression spined fractures. Finally, we diagnosed benign esophageal stricture with reflux esophagitis. She underwent laparoscopic partial esophagectomy in September 21, 2004, and the postoperative course was satisfactory. The pathological findings showed benign esophageal stricture caused by esophagitis. We report here a case of esophageal stricture following complete remission after chemotherapy for malignant lymphoma in an elderly patient.

DOI： 10.3143/geriatrics.43.531

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

The t(1;21)(p36;q22) is a recurrent chromosome abnormality associated with therapy-related acute myeloid leukemia (AML). Although involvement of RUNX1 has been detected by fluorescence in situ hybridization analysis, the partner gene has not been reported previously. We identified a novel RUNX1 partner gene, MDSI/EVI1-like-gene 1 (PRDM16), in an AML patient with t(1;21). Alternative splicing of the fusion gene generates five different fusion transcripts. In two of them, the PRDM16 reading frame is maintained in the fusion with RUNX1, suggesting that the RUNX1-PRDM 16 gene fusion results in the production of a protein that is highly homologous to the RUNX1-MDSI/EVI1 chimeric protein. It is suggested that PRDM16 and MDSI/EVI1 share a common molecular mechanism for the leukemogenesis of RUNX1-associated leukemia. Characterization of the RUNX1-PRDM16 fusion protein and comparison with the RUNX1-MDSI/EVI1 protein will facilitate the understanding of the mechanisms underlying RUNX1-associated leukemia. (c) 2005 Wiley-Liss, Inc.

DOI： 10.1002/gcc.20241

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

An 80-year-old man presented to the internist with fever, fatigue and leukocytosis up to 66.8x10(3)/mu l. Although a chronic myelogenous leukemia was initially suspected, he was diagnosed as metastatic bone marrow tumor with bone marrow necrosis from primary prostate cancer on the basis of the clinical and pathological findings. The serum concentrations of IL-6 and TNF-alpha were mildly elevated to 65.0 pg/ml and, 54.0 pg/ml respectively. It is probable that these humoral factors were partially responsible for the leukemoid reaction although other factors induced by the bone marrow necrosis with bone marrow metastasis of prostate cancer are also likely involved.

DOI： 10.2169/internalmedicine.44.1093

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記述言語：日本語   出版者・発行元：日本臨床血液学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC HEMATOLOGY  

Wilms tumor gene 1 product (WT1) has been recognized as an attractive target antigen of immunotherapy for various malignancies including leukemia. Because tumor-associated antigen-specific CD4(+) T lymphocytes undoubtedly play an important role in the induction of an antitumor immune response, we attempted to generate WT1-specific CD4(+) T lymphocytes in vitro and examined their antileukemia functions. A CD4(+) T-cell line, designated NIK-1, which proliferated and produced Th1 cytokines specifically in response to stimulation with the WT1-derived peptide, WT1(337-347) LSHLQMH-SRKH, in an HLA-DP5-restriced manner was established. NIK-1 exhibited cytotoxicity against HLA-DP5-positive, WT1-expressing leukemia cells but did not lyse HLA-DP5-negative, WT1-expressing leukemia cells or HLA-DP5-positive, WT1-negative cells. NIK-1 did not inhibit colony formation by normal bone marrow cells of HLA-DP5-positive individuals. This is the first report to describe WT1-specific and HLA class II-restricted CD4(+) T lymphocytes possessing direct cytotoxic activity against leukemia cells.

DOI： 10.1182/blood-2005-01-0413

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Objective. Because perforin is an essential cytolytic mediator of cytotoxic T lymphocytes (CTLs), it is important to understand the regulatory mechanisms of perforin expression in CTLs. In the present study, we investigated the relationship between cytotoxic activity, perforin expression, and cell-activated status of CD4(+) and CD8(+) CTLs.
Methods. Herpes simplex virus-specific CD4(+) CTL clones and Epstein-Barr virus-specific CD8(+) CTL clones were established, and their cytotoxic activities were examined in both the activated and resting phases. Perforin mRNA expression was examined by reverse transcriptase polymerase chain reaction quantitatively. Transcriptional regulation of perforin was examined by electrophoretic mobility shift assay.
Results. The degrees of cytotoxic activity of CD8(+) CTLs did not differ significantly between the two phases; however, CD4(+) CTLs in the activated phase appeared to be significantly more cytotoxic than those in the resting phase. Similarly, expression levels of perforin mRNA in activated and resting CD8(+) CTLs did not differ significantly, but activated CD4(+) CTLs appeared to express perforin more abundantly than resting CD4(+) CTLs. In addition, it appeared that binding of STAT5 to the perforin gene promoter was increased in activated CD4(+) CTLs compared to resting CD4(+) CTLs; however, there was no significant detectable difference of STAT5 binding activity to the perforin gene promoter between activated and resting CD8(+) CTLs.
Conclusions. The present study has revealed a difference in the control of perforin expression between CD4(+) and CD8(+) CTLs; that is, perforin is expressed constitutively in memory CD8(+) CTLs, but is dependent on cell activation in memory CD4(+) CTLs.

DOI： 10.1016/j.exphem.2005.04.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING LTD  

Recent advances in immunological and molecular technology have prompted proposals to change tumour classification and treatment strategies. Cell surface antigens are now easy to access, and tumour origins and clinical characteristics are now readily identifiable. However, in diffuse large B-cell lymphoma (DLBCL), one of the heterogeneous forms of haematological malignancy, the clinical significance of tumour surface antigens has not been well documented. We analysed the tumour surface antigens of 50 tumours from newly diagnosed DLBCL patients by flow cytometry in accordance with their clinical characteristics and followed the patients for a median 3.7 years. Statistical analysis showed that CD21 expression was significantly negatively associated with mortality in DLBCL (CD21 negative versus positive; relative risk = 2.36, P &lt; 0.05). As a result of these clinical observations, we generated CD21-overexpressed (CD21(+)) lymphoma cell lines after gene transfection and analysed tumour cell growth in vivo in immunocompromised mice. Mice challenged with vector-only transfectants and parental cells as controls died within 50 d. In contrast, mice injected with CD21(+) transfectants exhibited significantly reduced tumour growth and 83% survived long term (versus control groups; P &lt; 0.05). Interestingly, all established CD21(+) transfectants (six clones from different bulks) showed homotypic aggregation during in vitro cell culture, and anti-CD21 antibodies did not block this aggregation. Expression of CD21 is strongly associated with increased survival in DLBCL in vivo. CD21 expression may be indirectly concerned with the expression of additional cell adhesion molecules.

DOI： 10.1111/j.1365-2141.2004.05226.x

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

The antigenic diversity observed in many vaccine candidates is one of the difficulties to design effective malaria vaccine. Since it is prerequisite to survey genetic polymorphism of the vaccine candidate antigens for the vaccine development, it is necessary to establish efficient screening method to detect the genetic polymorphism from a large number of samples. Here, we have established efficient polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) method to detect nucleotide diversity of the malaria transmission-blocking vaccine candidates Pvs25 and Pvs28. We can distinguish all 4 haplotypes of Pvs25 by this method. By introducing BsmI-digestion step for Pvs28, we can distinguish 15/16 haplotypes by single electrophoresis. Since this method requires neither sequencing nor radioisotope labeling, it will be easy to transfer the method into a field based high throughput screening of genetic polymorphism. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.parint.2004.01.012

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS LTD  

Non-Hodgkin's lymphoma (NHL) has a wide biological heterogeneity with various cell origin and biological features. Recent WHO classification of lymphoid neoplasms gives importance to immunological and cytogenetic features in addition to morphologic aspects of tumors. Several investigators have performed NHL subclassification based on other biological features of tumor cells. It is extremely important to clarify the proliferation mechanism of tumor cells, and understanding this mechanism may provide insight not only into the biology of tumors but also into the treatment strategy for NHL. Therefore, research focused on the cell cycle is one of the major approaches to the biology and the oncogenesis of NHL. The Aurora kinase family recently identified from Drosophila melamogaster is believed to be an essential kinase involved in mitotic cell cycles. Several groups have reported that Aurora kinases are overexpressed in some solid tumors, suggesting that Aurora kinases may be involved in tumor survival and proliferation. Here, we focus on the role of Aurora-A kinase in the tumorgenesis of NHL using our recent research data, and discuss the possibility of Aurora-A as a new molecular target of NHL treatment.

DOI： 10.1080/10428190410001683615

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記述言語：日本語   出版者・発行元：日本臨床血液学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CARDEN JENNINGS PUBL CO LTD  

Imatinib mesylate and rituximab are molecularly targeted drugs against the BCR-ABL fusion protein and the CD20 antigen, respectively. Although these drugs have excellent anticancer effects, a major concern is drug resistance. We have investigated the case of a patient with Philadelphia chromosome-positive and CD20(+) acute lymphocytic leukemia who acquired resistance to imatinib and rituximab. Imatinib therapy resulted in prompt cytogenetic remission, but resistance developed shortly thereafter. Sequencing of the kinase domain of the ABL gene and allele-specific polymerase chain reaction analysis revealed a point mutation resulting in an E255V substitution that was present before the therapy. After the patient received mild chemotherapy followed by rituximab administration, hematologic and cytogenetic remission was sustained for 5.5 months. The recurrent leukemic cells after the rituximab therapy showed not only the E255V mutation in the ABL gene but also loss of the CD20 antigen due to impaired transcription of the CD20 gene. The results of 2-color flow cytometry analysis showed that a small population of CD20(-) leukemic cells existed before the imatinib therapy. These results suggest that leukemic subclones carrying a genetic perturbation of the targeted molecules for both imatimb and rituximab were present before the therapies. The preexistence of primary resistant clones suggests the inability of combination therapy with 2 molecularly targeted drugs to overcome drug resistance in leukemia. (C) 2004 The Japanese Society of Hematology.

DOI： 10.1532/ijh97.04033

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：英語   出版者・発行元：日本感染症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING LTD  

Non-Hodgkin's lymphoma (NHL) has a wide biological heterogeneity and shows extremely variable responses to therapeutic measures. However, markers that indicate disease activity and determine treatment strategies for this malignancy are little recognized. Using the differential display method, we have identified Aurora2/BTAK/STK15 , a centrosome-associated serine/threonine kinase, whose overexpression leads to centrosome amplification, chromosomal instability and transformation of mammalian solid tumours. Northern analysis with mRNA from a single tumour cell suspension of NHL confirmed that Aurora2/BTAK/STK15 was highly expressed in histologically aggressive types. To elucidate the function of Aurora2/BTAK/STK15 in NHL, Aurora2/BTAK/STK15 sense or antisense genes were transfected to B-cell lymphoma cell lines to generate overexpressed or under-regulated tumour cells. Aurora2/BTAK/STK15 antisense transfectant was barely established compared with a sense or vector-only transfectant. Two clones were finally established that exhibited a low proliferation rate and significantly increased G1 arrest compared with vector-only transfectants. Moreover, antisense oligo treatment in vitro showed that restriction of cell growth appeared in proportion to antisense oligo concentration. These results suggest that Aurora2/BTAK/STK15 is an effective candidate to indicate not only disease activity but also tumorigenesis of non-Hodgkin's lymphoma. Retardation of tumour cell growth resulting from the restriction of this gene's functions may be a novel therapeutic approach for non-Hodgkin's lymphoma.

DOI： 10.1046/j.1365-2141.2003.04311.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CARDEN JENNINGS PUBL CO LTD  

A 29-year-old man developed diffuse large B-cell lymphoma in a subpectoral pacemaker pocket that 6 years previously had been created in the chest for a titanium-covered pulse generator. The patient had an 8-cm-diameter dark red tumor with necrotic tissue on a keloidal surgical scar in the left side of the chest. Left axillary lymphadenopathy also was present. Laboratory studies showed an increased level of soluble interleukin 2 receptor and a normal level of lactose dehydrogenase. A biopsy specimen showed a diffuse large B-cell phenotype and monoclonal immunoglobulin H gene rearrangement. A gallium scintigraphy study showed abnormal accumulation in the left chest and left axilla. On the basis of these findings, we diagnosed diffuse large B-cell lymphoma, stage II. The patient received THP-COP chemotherapy (pirarubicin, cyclophosphamide, vincristine, and prednisolone) and radiotherapy, achieved complete remission, and was free of disease for 16 months after treatment. This case suggests that there was a relationship between the development of non-Hodgkin's lymphoma and the presence of chronic inflammation in the pulse generator pocket. (C)2003 The Japanese Society of Hematology.

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記述言語：日本語   出版者・発行元：(一社)日本病院薬剤師会  

21歳男.乳幼児期に血友病Aと診断され,定期的に第VIII因子の投与を受けていた.HIV抗体陽性の確定診断で抗HIV剤の投与を受けていたが,内服コンプライアンスの不全からウイルスは高度耐性となった.全身倦怠感,食欲不振,下痢,体重減少により入院した.後天性免疫不全症候群(サイトメガロウイルス(CMV)腸炎,栄養吸収不全)と診断した.抗生物質,抗ウイルス薬が投与開始されたが,体力の消耗が激しく,内服が不可能になり抗HIV薬も中止となった.中心静脈栄養ルート挿入後,注射に変更可能な薬剤は変更し,モルヒネ,ステロイドの投与も開始となった.ガンシクロビルの投与を開始してから解熱し,状態も落ち着いたため,IVH抜去後,内服薬に順次変更となった

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記述言語：日本語   出版者・発行元：The Japanese Society of Hematology  

症例は77歳，男性。左頸部腫瘤を主訴に近医に入院し，非Hodgkinリンパ腫，diffuse large cell type, Ann Arbor病期IVと診断され当院に転院した。左腋窩リンパ節生検細胞の表面マーカー検査では，CD5, 7, 21などのリンパ系細胞マーカー以外にCD11b, 33, 34などの骨髄系細胞マーカーも陽性であった。しかし，当初は発症部位および生検組織の病理組織像などより，悪性リンパ腫と診断し，THP-COP療法を施行し著効を得た。その後，免疫組織化学検査ではmyeloperoxidase, chloroacetate esterase染色は陰性であったが，MT1 (CD43)染色が陽性であり，さらに免疫グロブリン遺伝子およびT細胞レセプター遺伝子の再構成を認めないことが判明し，先の細胞表面マーカー検査結果と総合的に判断して，顆粒球肉腫(granulocytic sarcoma)と診断を改めた。治療はTHP-COP療法を継続して完全寛解を得た。しかし，2カ月後急性骨髄性白血病(M1)を発症し，DCP療法中肺炎を併発して死亡した。

DOI： 10.11406/rinketsu.43.378

PubMed

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その他リンク： https://jlc.jst.go.jp/DN/JALC/00154001410?from=CiNii

記述言語：日本語   出版者・発行元：The Japanese Society of Internal Medicine  

症例は51歳,女性.左頸部無痛性腫瘤を認め,生検の結果diffuse large B-ce11 lymphomaと診断され,生検細胞の染色体検査の結果t (8; 14)とt (14; 18)の2つの染色体異常を同時に認めた.腫瘍細胞を用いたSouthern blotでは, c-mycとbcl-2の再構成バンドを確認し, FISH法では, c-mycとIgH癒合シグナル及びbcl-2とIgH癒合シグナルを認めた. bc1-2とc-mycの転座を同時に認める過去の症例は予後不良症例が多数であり,この転座を有する症例の病態・予後を考察するうえで興味深い症例であると思われる.

DOI： 10.2169/naika.90.2485

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その他リンク： https://jlc.jst.go.jp/DN/JALC/00152682499?from=CiNii

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC HEMATOLOGY  

The incidence of follicular lymphoma differs significantly between white and Japanese individuals. Translocation between the BCL-2 and immunoglobulin heavy chain genes is detected in 85% to 90% of all follicular lymphomas in whites. Recently, BCL-2/J(H) translocation was detected in peripheral blood lymphocytes from more than 50% of healthy white individuals. To clarify the reason for the difference in incidence of follicular lymphoma between whites and Japanese, the frequency of BCL-2/JH translocation in peripheral blood lymphocytes of healthy Japanese individuals was compared with that of German individuals. The prevalence of BCL-2/JH translocation in Japanese adults appeared to be significantly lower than that in German adults. The present data suggest that the low frequency of BCL-2/J(H) translocation in the Japanese general population may be one of the major reasons for the difference in incidence of follicular lymphoma between whites and Japanese. (C) 2001 by The American Society of Hematology.

DOI： 10.1182/blood.V98.2.486

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC HEMATOLOGY  

Clinical risk factor models such as the International prognostic Index are used to identify diffuse large B-cell lymphoma (DLB-CL) patients with different risks of death from their diseases. To elucidate the molecular bases for these observed clinical differences in outcome, differential display was used to identify a novel gene, termed BAL (B-aggressive lymphoma), which is expressed at significantly higher levels in fatal high-risk DLB-CLs than in cured low risk tumors. The major BAL complementary DNA encodes a previously uncharacterized 88-kd nuclear protein with a duplicated N-terminal domain homologous to the non- histone portion of histone-macroH2A and a C-terminal alpha-helical region with 2 short coiled-coil domains. Of note, the BAL N-terminus and secondary structure resemble those of a recently identified human protein, KIAA1268. In addition, both BAL and KIAA1268 map to chromosome 3q21, further suggesting that these genes belong to a newly identified family. BAL is expressed at increased levels in DLB-CL cell lines with an activated peripheral B cell, rather than a germinal center cell, phenotype. This observation and the characteristic dissemination of high risk DLB-CLs prompted studies regarding the role of BAL in B-cell migration. In classical transwell assays, stable BAL-overexpressing B-cell lymphoma transfectants had significantly higher rates of migration than vector-only transfectants, indicating that the risk-related BAL gene promotes malignant B-cell migration. (Blood. 2000;96:4328-4334) (C) 2000 by The American Society of Hematology.

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記述言語：英語   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：日本語   出版者・発行元：The Japanese Society of Internal Medicine  

症例は82歳,男性. 1997年11月右肩関節に皮膚腫瘤,左膝関節に骨破壊が出現.生検にて両病変部にリンパ球の腫瘍性の浸潤を認めた.免疫組織染色およびフローサイトメトリーによる解析では,皮膚・骨ともに小型のCD8陽性T細胞が約9割を占めB細胞は1割に満たなかった.一方,腫瘤組織を用いたサザンブロット解析ではTcR遺伝子の再構成は認めず, IgH遺伝子の再構成を認めたことから本症例をCD8⁺-T-cell-rich B-cell lymphomaと診断した.

DOI： 10.2169/naika.89.992

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その他リンク： http://search.jamas.or.jp/link/ui/2000254948

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MUNKSGAARD INT PUBL LTD  

Stromal cell-derived factor-1 (SDF-1) is a chemokine produced by bone marrow stromal cells which plays an important role in B-lymphopoiesis and the homing of hematopoietic stem cells to the bone marrow. In the present study, we investigated the role of SDF-1 and its receptor, CXCR4, in the chemotactic interaction between non-Hodgkin B-lymphoma cells and lymph node stromal cells. SDF-1 mRNA was abundantly expressed in stromal cells isolated from the lymph nodes of patients with malignant lymphoma. All B-lymphoma cells freshly isolated from these patients and most laboratory B-lymphoma cell lines, including follicular, diffuse large, and Burkitt's lymphoma cells, expressed surface CXCR4 and migrated in the presence of recombinant human SDF-1 alpha. Chemotaxis assays revealed that CXCR4-positive (but not CXCR4-negative) B-lymphoma cells migrated towards lymph node stromal cells, and this migration was almost completely inhibited by the addition of anti-CXCR4 monoclonal antibody to the lymphoma cells or of anti-SDF-1 neutralizing antibody to the culture supernatant of the stromal cells. Down-regulation of surface CXCR4 was detected in B-lymphoma cells which migrated towards the stromal cells but not in those which showed no migratory response. In addition, contact between the lymphoma cells and the stromal cells resulted in down-regulation of surface CXCR4 on the lymphoma cells. These data strongly suggest that SDF-1/CXCR4 is the main chemokine system involved in the chemotactic interaction between B-lymphoma cells and lymph node stromal cells.

DOI： 10.1034/j.1600-0609.2000.90147.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC HEMATOLOGY  

Protein tyrosine phosphatases (PTP) regulate the proliferation, differentiation, and viability of lymphocytes by modulating their signaling pathways. By using the differential display assay, we have cloned a putative receptor-type PTP, which is predominantly expressed in B-lymphoid tissues (lymph nodes and spleen). This PTP, termed PTPROt (truncated), is a tissue-specific alternatively-spliced form of a human epithelial PTP, PTPRO (PTPU2/GLEPP1). Whereas the epithelial PTPRO includes an approximate to 800-amino acid extracellular domain, the major (3 kb) PTPROt cDNA predicts a unique 5' untranslated region and truncated (8 amino acids) extracellular domain with a conserved transmembrane region and single catalytic domain. PTPROt cDNAs encode functional similar to 47-kD and similar to 43-kD PTPs, which are most abundant in normal naive quiescent B cells and decreased or absent in germinal center B cells and germinal center-derived diffuse large B-cell lymphomas. Because PTPROt was predominantly expressed in naive quiescent B cells, the enzyme's effects on cell-cycle progression were examined. When multiple stable PTPROt sense, antisense, and vector only B-cell transfectants were grown in reduced serum and synchronized with nocodazole, PTPROt sense clones exhibited markedly increased G0/G1 arrest. Taken together, these data implicate PTPROt in the growth control of specific B-cell subpopulations. (C) 1999 by The American Society of Hematology.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC IMMUNOLOGISTS  

The present study was undertaken to clarify the mechanisms of cytotoxicity mediated by virus-specific human CD4(+) CTLs using the lymphocytes of family members with a Fas gene mutation. CD4(+) CTL bulk lines and clones directed against HSV-infected cells were established from lymphocytes of a patient with a homozygous Fas gene mutation and of the patient's mother. HSV-specific CD4(+) CTLs generated from lymphocytes of the patient and her mother exerted cytotoxicity against HSV-infected cells from the patient (Fas(-/-)) and from her mother (Fas(+/-)) to almost the same degree in an HLA class II-restricted manner. mRNAs for the major mediators of CTL cytotoxicity, Fas ligand, perforin, and granzyme B, were detected in these CD4(+) CTLs using the RT-PCR and flow cytometry, The cytotoxicity of the HSV-specific CD4(+) CTLs appeared to be Ca2+-dependent and was almost completely inhibited by concanamycin A, a potent inhibitor of the perforin-based cytotoxic pathway. Although the Fas/Fas ligand system has been reported to be the most important mechanism for CD4(+) CTL-mediated cytotoxicity in the murine system, the present findings strongly suggest that granule exocytosis, not the Fas/Fas Ligand system, is the main pathway for the cytotoxicity mediated by HSV-specific human CD4(+) CTLs.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC HEMATOLOGY  

The mechanism underlying the cytotoxicity mediated by a human CD4(+) cytotoxic T-lymphocyte (CTL) clone directed against a peptide derived from the acute myelogenous leukemia-associated fusion protein, DEK-CAN, was investigated. A DEK-CAN fusion peptide-specific CD4(+) Th0 CTL clone, designated HO-1, was established from the peripheral blood lymphocytes of a healthy individual. HO-1 exerted direct but not "innocent bystander" cytotoxicity within 2 hours. The cytotoxicity mediated by HO-1 was completely Ca2+-dependent. Because HO-1 lysed peptide-loaded Fas-deficient target cells derived from a patient with a homozygous Fas gene mutation, its cytotoxicity appeared to be mediated by a Fas-independent pathway. in addition, its cytotoxicity was only partially inhibited by treatment with concanamycin A and strontium ions, which are inhibitors of the perforin-based cytotoxic pathway. Although membrane-bound type of tumor necrosis factor-alpha (TNF-alpha) was expressed on HO-1. an anti-TNF-alpha antibody had no effect on HO-1-mediated cytotoxicity. HO-1 expressed mRNA for apoptosis-inducing mediators, including perforin, granzyme B, Fas ligand, TNF-alpha, and lymphotoxin; however, no DNA fragmentation was detected in target cells incubated with HO-1 by 5-[I-125]Iodo-2'-deoxyuridine release assay and agarose gel electrophoresis of DNA. Although it has been suggested that the Fas/Fas ligand system is the main pathway by which CD4(+) CTL-mediated cytotoxicity is exerted in murine systems, HO-1 produced peptide-specific and HLA-restricted cytotoxicity via a Fas-independent and nonapoptotic pathway. The present study thus describes a never mechanism of cytotoxicity mediated by CD4(+) CTL. (C) 1999 by The American Society of Hematology.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC HEMATOLOGY  

It has been reported that reactivation of human herpesvirus-6 (HHV-6) causes a failure of hematopoiesis. To clarify the mechanisms of bone marrow suppression induced by HHV-6 infection, it is necessary to establish an in vitro model of HHV-6 infection in hematopoietic progenitor cells. We have established two novel Philadelphia chromosome-positive myeloid cell lines, SAS413 and SAS527, which possess different hematologic characteristics and show distinct susceptibility to infection by HHV-6, from a patient with blast crisis of chronic myelogenous leukemia (CML). HHV-6 subgroup A (HHV-6A) showed marked replication in SAS413, forming syncytia and inducing cell lysis in short-term culture. On the other hand, HHV-6A-inaculated SAS527 continued to proliferate without cell lysis and only a few cells showed HHV-6 antigen expression. In contrast to HHV-6A infection, inoculation with HHV-6 subgroup B (HHV-6B) did not induce any cytopathic effect (CPE) or viral antigen expression in either of the cell lines. Although HHV-6B replication was undetectable, the presence of the HHV-6 genome in both cell lines was shown by polymerase chain reaction (PCR) during culture for more than 10 months, suggesting that HHV-6B latently infected SAS413 and SAS527. Phorbol ester treatment of SAS527 latently infected with HHV-6B resulted in reactivation of HHV-6, as shown by the appearance of a CPE, positive reactivity for the HHV-6 antigen, and isolation of infectious HHV-6. These novel cell lines should be useful for studying the mechanisms of HHV-6-induced hematopoietic failure and HHV-6 latency and reactivation, as well as differentiation, of the myeloid cell lineage. (C) 1999 by The American Society of Hematology.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W B SAUNDERS CO  

Variants of the CD44 cell-surface adhesion molecule include additional sequences encoded by combinations of exons from the membrane proximal domain (exons 6-14). Preliminary studies suggest that these additional variable membrane proximal sequences may alter the ligand specificity, glycosylation, and biologic function of CD44. In earlier studies, we found that primary extranodal and widely disseminated aggressive non-Hodgkin's lymphomas (NHLs) and normal activated B cells expressed a directly spliced exon 10-containing variant (CD44ex10), whereas normal resting B cells expressed larger exon 10-containing variants (CD44ex10-14 and CD44ex7-14). To obtain additional information regarding the function of exon 10-containing CD44 variants in aggressive NHL, we generated aggressive NHL transfectants that expressed CD44ex10, CD44ex10-14, CD44ex7-14, the standard CD44 isoform (CD44H), or vector alone, and evaluated the local tumorogenicity, aggregation, and metastatic potential of these transfectants. CD44ex10 aggressive NHL transfectants were more likely to cause local tumor formation in nude mice than transfectants expressing the larger exon 10-containing variants, CD44H, or vector alone. In addition, cell suspensions derived from CD44ex10 local tumors exhibited far greater homotypic aggregation than those obtained from other CD44 or vector-only local tumors. In nude mice that received CD44ex10 transfectants, distant metastases were also significantly more likely to develop than in animals that were given either the CD44ex10-14, CD44ex7-14, CD44H, or vector-only transfectants. These data provide the first evidence that the directly spliced exon 10-containing CD44 variant (CD44ex10) has a unique biologic function in aggressive NHL. (C) 1998 by The American Society of Hematology.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SOC GENERAL MICROBIOLOGY  

Recently, data demonstrating that CD4 is an essential component of the receptor for human herpesvirus 7 (HHV-7) as well as for human immunodeficiency virus have been accumulating. Since gangliosides and phorbol esters are known to induce selective down-modulation of cell surface CD4 expression, it might be expected that treatment with these agents would interfere with HHV-7 infection of CD4(+) T cells. The present study, undertaken to verify this possibility, demonstrated that addition of monosialoganglioside-GM1 or 12-O-tetradecanoylphorbol 13-acetate effectively induced disappearance of CD4 from the cell surface and also reduced HHV-7 infectivity, as judged by the CPE on virus-infected cells and studies of indirect immunofluorescence, TCID50 and semi-quantitative PCR of the HHV-7 genome. Taken together with previous studies, the present data strongly suggest that the CD4 molecule is a critical component of the receptor for HHV-7.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC IMMUNOLOGISTS  

This study was undertaken to investigate the effects of newly isolated T lymphotropic viruses, human herpesvirus (HHV)-6 and HHV-7, on CD4(+) T cells. We first examined changes in surface molecule expression on CD4(+) T cells after infection with HHV-6 or HHV-7 by flow cytometry. Among surface molecules examined, CD3 expression appeared to decline markedly after infection with HHV-6 variant A (strain U1102) but the decreased level of CD3 expression after infection with HHV-6 variant B (strain Z29) was slight. Impairment of surface CD3 expression on HHV-6 variant A-infected cells was also demonstrated by measuring intracellular free Ca2+ concentration in response to anti-CD3 mAb. In contrast, HHV-7 infection induced a marked loss of surface CD4 expression, but the decline of CD3 expression was slight. Cytotoxic activity of virus-specific CD4(+) CTL clones decreased after infection with both HHV-6 variant A or HHV-7 but the degree of reduction of cytotoxicity by HHV-6 variant B was not significant. Addition of lectin restored the cytotoxicity of HHV-7-infected CTL but not that of HHV-6 variant A-infected CTL. Northern blot analysis and immunoprecipitation showed that infection with HHV-6 and HHV-7 did not affect the transcription and protein synthesis of CD3 and CD4. These findings suggest that both HHV-6 and HHV-7 may directly cause T cell immunodeficiency but that the mechanisms of CD4(+) T cell dysfunction mediated by HHV-6 and HHV-7 are different.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL SCIENCE LTD  

Two continuously growing cell lines, designated YOS-M and YOS-B, were established simultaneously from a patient with Philadelphia (Ph1) chromosome-positive chronic myelogenous leukaemia (CML) in myeloid blast crisis. Both YOS-M and YOS-B had the Ph1 chromosome and identical additional chromosome abnormalities, which were not detected in the chronic phase. Cytochemical analysis showed that YOS-M was significantly positive for peroxidase, whereas YOS-B was entirely negative. YOS-M expressed myeloid-associated antigens (CD14, CD33) as well as CD4, CD25 and CD34. The surface phenotype of YOS-M was identical to that of the leukaemic blasts found in the patient. On the other hand, YOS-B expressed mature B-cell markers, CD19, CD20, CD21 and surface immunoglobulin, but not myeloid-associated antigens. These two cell lines showed an identical rearrangement pattern of the break point cluster region on chromosome 22, but rearrangement of the immunoglobulin heavy chain gene was detected only in YOS-B. These findings provide definite evidence that CML cells still have the capability to differentiate and mature along different haematopoietic cell lineages even after blast crisis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC MICROBIOLOGY  

In order to clarify the protective immune responses against a newly identified herpesvirus, human herpesvirus 6 (HHV-6), we established HHV-6-specific human T-cell clones and examined their functional properties. Five CD3+ CD4+ CD8- T-cell clones, which proliferated in response to stimulation with two different strains of HHV-6 in the presence of autologous antigen-presenting cells but not with herpes simplex virus type 1 or human cytomegalovirus, were established from peripheral blood lymphocytes of a healthy individual. The proliferative response of all T-cell clones to HHV-6 antigen was inhibited by addition of anti-HLA-DR monoclonal antibody, indicating that these clones were human leukocyte antigen (HLA) class II DR restricted. Of the five clones, two lysed HHV-6-infected autologous lymphoblasts, but not HHV-6-infected allogeneic cells or natural killer-sensitive K562 cells (group 1); one showed cytotoxicity against HHV-6-infected autologous lymphoblasts as well as HHV-6-infected allogeneic cells and K562 cells (group 2); and the remaining two showed no cytotoxic activity (group 3). The cytotoxic activity of group 1 was inhibited by addition of anti-HLA-DR monoclonal antibody to the culture, whereas this monoclonal antibody had no effect on the cytotoxicity of group 2 and did not induce the cytotoxicity of group 3. Perforin, which is one of the mediators of cytotoxicity, was abundantly expressed in group 1 and 2 clones. Moreover, all groups of clones produced gamma interferon after culture with antigen-presenting cells followed by HHV-6 antigen stimulation. These results suggest that HHV-6-specific CD4+ T cells have heterogeneous functions.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

In order to clarify the cellular tropism of human T-cell leukemia virus type I (HTLV-1) and the effects of HTLV-1 infection on T-cell functions, we investigated the infectiousness of HTLV-1 on T cells bearing T-cell receptor (TCR) gamma-delta and functional alterations of the HTLV-1-infected TCR-gamma-delta+ T cells. CD3+CD4-CD8-TCR-gamma-delta+ T-cell clones which possessed cytotoxicity were co-cultured with a HTLV-1-producing T-cell line. After several weeks, integration of HTLV-1 proviral DNA in TCR-gamma-delta+ T cells was detected by Southern blot analysis. During the continuous culture of HTLV-1-infected TCR-gamma-delta+ T-cell clones, 2 distinct phases were observed in terms of cytotoxic activity and expression of the CD3-TCR-gamma-delta complex. Early after HTLV-1 infection, TCR-gamma-delta+ T cells lost their spontaneous cytotoxicity, but this was restored by the addition of lectin. At this time, no differences were observed in the expression of various surface molecules between HTLV-1-infected and uninfected parent cells, except for increased expression of CD25 on HTLV-1-infected cells. At about 30 weeks after HTLV-1 infection, the cytotoxicity of HTLV-1-infected cells was almost completely lost, even in the presence of lectin, and expression of the CD3-TCR-gamma-delta complex on the cell surface was markedly decreased. Concomitant with the decreased expression of CD3-TCR-gamma-delta complexes, a decrease in the elevation of cytoplasmic Ca2+ concentration induced by anti-CD3 and anti-TCR monoclonal antibodies (MAbs) was also observed. Our present findings thus show that HTLV-1 can infect TCR-gamma-delta+ T cells, and that consequently their functions are profoundly affected through 2 distinct phases.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CENTER ACAD PUBL JAPAN  

The proliferative response of peripheral blood mononuclear cells (PBMC) from healthy adults to human herpesvirus-6 (HHV-6) was examined. It was found that PBMC from 13 of 14 HHV-6-seropositive adults apparently proliferated in response to stimulation with HHV-6 antigen in contrast to the lack of response of cord blood mononuclear cells. In order to confirm the presence of HHV-6-specific memory T cells in the peripheral blood of healthy adults, we established HHV-6-specific T-cell clones from an HHV-6-seropositive individual. CD4+ T-cell clones generated from HHV-6-stimulated PBMC were found to proliferate upon stimulation with HHV-6 in the presence of autologous antigen-presenting cells, but not in response to herpes simplex virus type 1 antigen or mock-infected control antigen. These results indicate that a T-cell immune response against HHV-6 infection is generally present in healthy adult populations.

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：OXFORD UNIV PRESS  

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記述言語：英語   出版者・発行元：(一社)日本血液学会-東京事務局  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/JCO.2018.36.15_suppl.e19534

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本医療薬学会  

抗がん剤の調製から投与までの医療従事者に対する抗がん剤曝露対策について検討した。試験薬剤にはシクロホスファミド(CPA)1バイアル、およびパクリタキセル(PTX)1バイアルを用いた。試験薬剤の調製には、抗がん剤調製業務に携わる薬剤師5名(抗がん剤調製経験1〜6年)が行った。投与から廃棄までの操作は、外来化学療法室に勤務する看護師5名(看護師勤務経験10〜32年)が行った。安全キャビネット内作業面上は、介入前後ともにCPAは限界以下であった。点滴台下は、介入前の手技では、1.67ng/cm2検出したが、介入後は検出限界以下であった。安全キャビネット内作業面上は、介入前後ともにPTXを、それぞれ0.089ng/cm2、0.070ng/cm2検出した。点滴台下は、介入前の手技では、PTXを0.077ng/cm2検出したが、介入後は検出限界以下であった。

DOI： 10.5649/jjphcs.41.811

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(公社)日本化学療法学会  

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記述言語：日本語   出版者・発行元：(公社)日本化学療法学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：科学評論社  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2013286820

記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本エイズ学会  

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記述言語：日本語   出版者・発行元：科学評論社  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2012333050

記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語  

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：OXFORD UNIV PRESS  

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記述言語：日本語   出版者・発行元：Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

Ehime Priority Hospitals of Cancer Care Network (Ehime Cancer Kyoten Hospitals) regularly have meetings to discus the current problems in cancer care in Ehime Prefecture. We established three subcommittees: "Registration of Cancer Incident," "Critical Paths for the Management of Patients with Cancer," and "Palliative Care for Patients with Advanced Cancer" to exchange our opinions. We recently set up a new subcommittee related to the physical and spiritual care of patients undergoing chemotherapy treatment, "A Subcommittee dealing with Cancer Chemotherapy and its Management". "This subcommittee has tried to identify current problems with chemotherapy for outpatients in each institution through questionnaire and analysis. As a result of this survey, it was found that Ehime Priority Hospitals have total of seventy-three beds for outpatients undergoing chemotherapy, and that they performed chemotherapy 19, 671 times in 2008. A total of eight oncology physicians and sixteen oncology nurses were engaged in performing chemotherapy in this system. The questions patients most frequently asked during chemotherapy concerned the management of therapy-related complications, dealing with problems at night and during holidays after chemotherapy, and financial problems related to the costs of treatment. In this study we found three issues that need to be managed in Ehime Priority Hospitals. First, for the nursing of outpatients undergoing chemotherapy, more staff engaged in different types of care is required. Second, a new system to deal with emergencies at night and during holidays after chemotherapy is necessary, because Ehime Priority Hospitals use the same system to deal with chemotherapy patients as for other patients. Third, cooperation between pharmacies and out-clinics is important for patient compliance during chemotherapy, especially for the administration of oral anti-tumor agents. Ehime Priority Hospitals of Cancer Care Network is trying to improve each institution while dealing with these problems.

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

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J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

82歳男。四肢の皮下出血・腫脹が出現し、検査所見でPT正常、APTTは81.8秒と延長しており、第VIII因子活性が検出感度以下、第VIII因子インヒビターは30.4BU/mlと高値であった。後天性血友病と診断し、prednisolone(PSL)60mg/日を開始したところ、1ヵ月後には第VIII因子活性が150%まで増加し、第VIII因子インヒビターも消失し、皮下出血も消失した。しかし、PSL漸減により第VIII因子活性が低下し、第VIII因子インヒビターが出現するため、難治性と考えcyclosporine A 100mg/日を追加した。その結果、PSL減量による再燃はなくなったが、治療開始10ヵ月頃より右上腕と左大腿部に皮下腫瘤が出現し、次第に発赤と熱感を伴うようになった。超音波所見より筋膿瘍を疑い穿刺吸引を行ったところ、混濁した膿が採取された。グラム染色でグラム陽性桿菌が検出され、好酸性染色で陽性を示したことから、ノカルジア属であることが示唆された。ST合剤開始により速やかに改善し、後日起因菌はNocardia brasiliensisと同定された。

DOI： 10.11406/rinketsu.50.495

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その他リンク： http://search.jamas.or.jp/link/ui/2009352399

記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

66歳女。1ヵ月前に右鎖骨部腫瘤が出現し、その後増悪した。CTでは右鎖骨に骨破壊を伴う6cm大の腫瘤を認め、内部に石灰化を伴っていた。生検でCD20陽性diffuse large B cell lymphomaとの診断が得られた。全身検索のGaシンチグラフィーでは右鎖骨、右大腿骨、右膝関節、左下腿に異常集積を認め、X線およびCTでは右大腿骨、左・右下腿に異常所見はなかったが、MRIでは右大腿骨にT1強調像で低信号、T2強調像で低信号域の中に一部高信号を認めた。CHOP療法を開始したところ腫瘤は速やかに縮小し、開始7日目にRituximabを投与したが、同日深夜にトイレで立ち上がった際に左脛骨、腓骨遠位部、右大腿骨転子部を骨折した。画像所見より病的骨折と考え、化学療法による骨髄抑制から回復した後に観血的接合術を施行した。その後、R-CHOP療法を繰り返し、現在は右鎖骨腫瘤は縮小して新たな骨形成も認め、Gaシンチでも異常集積は認めない。

DOI： 10.11406/rinketsu.50.187

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その他リンク： http://search.jamas.or.jp/link/ui/2009352342

記述言語：日本語   出版者・発行元：(株)南江堂  

64歳男。39℃に及ぶ発熱と全身倦怠で近医受診し、上気道炎と診断され抗生物質の内服加療を受けたが改善しないため当科紹介受診となった。両側頸部リンパ節で5mm弱のものを数個触知し、扁桃腺炎による発熱と考え抗生物質の点滴を行なったが解熱せず、下部消化管内視鏡で回腸末端部に発赤を伴う小隆起性病変の散在を認めた。生検より異型リンパ球の浸潤が粘膜筋板部から粘膜下層に拡大し、血管内皮腫大が著明な血管増生と淡明な細胞質をもつ大型の異型細胞を多数認め、免疫染色でCD3とUCHL1は陽性、CD20とCD79の陰性であった。以上より、血管免疫芽球性T細胞リンパ腫(AILT)stageIV、IPI 2と診断してCHOP療法を施行した。1コース終了後に解熱、全身倦怠感の改善、頸部リンパ節腫大の改善を認め、2コース終了後には回腸末端部の隆起病変は消失した。6コース施行して現在寛解を維持した。

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その他リンク： http://search.jamas.or.jp/link/ui/2009138560

記述言語：日本語   出版者・発行元：(株)南江堂  

64歳男。陰部に違和感を自覚し、近医で陰茎根部の硬結、左鼠径部のリンパ節腫大を指摘され、生検で悪性リンパ腫を疑われ当院紹介入院となった。CTでは陰茎根部に径3cmのややlow densityの陰影を、MRIのT2強調像では陰茎全体に低吸収域を認めた。Gaシンチグラフィーでは陰茎根部と左鼠径部リンパ節に加え、上方の骨盤内にも集積を認めた。生検組織標本では鼠径部リンパ節、陰茎根部ともびまん性にやや大型のリンパ腫細胞が浸潤しており、CD20染色は陽性であった。Stage IIEのnon-Hodgkin&#039;s lymphoma、diffuse large B-cell typeと診断し、R-CHOP療法を開始した。1コース終了時点で陰茎根部の硬結と鼠径部リンパ節の縮小を認め、以後化学療法を計8コース行い、寛解を維持している。

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2009072566

記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：OXFORD UNIV PRESS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：OXFORD UNIV PRESS  

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J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：日本医療薬学会  

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記述言語：日本語   出版者・発行元：科学評論社  

CiNii Books

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：日本臨床社  

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その他リンク： http://search.jamas.or.jp/link/ui/2007191961

記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

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記述言語：日本語   出版者・発行元：日本老年医学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2006318953

記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：認定内科専門医会  

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記述言語：日本語   出版者・発行元：日本内科学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2006051486

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：OXFORD UNIV PRESS  

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記述言語：日本語   出版者・発行元：南江堂  

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その他リンク： http://search.jamas.or.jp/link/ui/2005191654

記述言語：日本語   出版者・発行元：医歯薬出版  

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その他リンク： http://search.jamas.or.jp/link/ui/2005094547

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語  

A 21-year-old man with an 8-year history of acquired immunodeficiency syndrome (AIDS) presented with abdominal pain, jaundice and dark urine. Laboratory data on admission revealed cholestasis. The total bilirubin concentration was 10.0 mg/dL. Alanine transaminase and aspartate transaminase were 198 IU/L and 195 IU/L, respectively. The serum alkaline phosphatase level was 2724 IU/L. γ-Glutamyl transferase was 1770 IU/L. Abdominal ultrasonography and computed tomography revealed dilation of the common bile duct and intrahepatic ducts without gallstones. Endoscopic retrograde cholangiopancreatography showed dilation of the common bile duct up to the level of the ampulla of Vater with partial stenosis. Endoscopic sphincterotomy was performed. The abdominal pain and jaundice resolved immediately and the liver function tests were significantly improved. The patient developed a subarachnoid hemorrhage and died of respiratory arrest 2 months after the endoscopic sphincterotomy.

DOI： 10.1111/j.1443-1661.2004.00344.x

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記述言語：日本語  

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記述言語：英語   出版者・発行元：NATURE PUBLISHING GROUP  

A 61-year-old man with angioimmunoblastic lymphoma in first complete remission underwent autologous peripheral blood stem cell transplantation. At 1 month post transplant, asymptomatic large granular lymphocytosis developed. The surface marker profile of the cells was CD3+CD8+CD56-CD57+. The disease course was chronic and indolent. The patient remains in complete remission from angioimmunoblastic lymphoma more than 6 months post transplant with persistent large granular lymphocytosis (lymphocyte count, 5-15 x 10(9)/l). Although post transplantation T-cell lymphoproliferative disorders have mostly occurred in allogeneic transplantation recipients and presented as aggressive lymphomas/leukemias, we suggest that chronic indolent T-cell large granular lymphocytic leukemia can occur after autologous stem cell transplantation.

DOI： 10.1038/sj.bmt.1704298

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語   出版者・発行元：AMER ASSOC IMMUNOLOGISTS  

Recent studies have demonstrated that human herpesvirus 6 (HHV-6) and HHV-7 interact with HIV-1 and alter the expression of various surface molecules and functions of T lymphocytes. The present study was undertaken to clarify whether coreceptors for HIV-1, CXCR4 and CCR5, are necessary for HHV-6 and HHV-7 infection. Although CXCR4 and CCR5 appeared not to be the coreceptors for these viruses, marked down-regulation of CXCR4, but not CCR5, was detected in HHV-6 variant A (HHV-6A)-, HHV-6 variant B (HHV-6B)-, and HHV-7-infected cells. Down-regulation of CXCR4 resulted in impairment of chemotaxis and a decreased level of elevation of the intracellular Ca2+ concentration in response to stromal cell-derived factor-1. Northern blot analysis of mRNAs extracted from HHV-6A-, HHV-6B-, and HHV-7-infected CD4(+) T lymphocytes demonstrated a markedly decreased level of CXCR4 gene transcription, but the posttranscriptional stability of CXCR4 mRNA was not significantly altered. These data demonstrate that unlike HIV-1, HHV-6 and HHV-7 infections do not require expression of CXCR4 or CCR5, whereas marked down-regulation of CXCR4 is induced by these viruses, suggesting that HHV-6 and HHV-7 infections may render CD4(+) T lymphocytes resistant to T lymphocyte-tropic HIV-1 infection.

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Although it is well known that CD8+ cytotoxic T lymphocytes (CTLs) play an important role in the suppression of cancer cell growth, the significance of CD4+ CTLs in resistance to cancer is obscure. In an attempt to elucidate the role of CD4+ CTLs in immunosurveillance of chronic myelogenous leukemia (CML), we examined the immunologic functions of bcr-abl b3a2 fusion peptide- specific CD4+ CTL clones. Seven CD4+ T-cell clones that responded to stimulation with b3a2 peptide, but not with b2a2 peptide or physiological counterparts bcr b364 and abl 1A-a2 peptides, were established from two healthy individuals. Restriction elements of these clones were HLA- DRB1*0901. These CD4+ T-cell clones exhibited b3a2 peptide-specific and HLA-DRB1*0901-restricted cytotoxicity and produced interleukin-3 (IL-3), IL- 4, IL-10, interferon-γ, tumor necrosis factor-α, and granulocyte- macrophage colony-stimulating factor in response to bcr-abl peptide stimulation, indicating they were Th0 clones. The numbers of HLA-DRB1*0901- positive b3a2, but not those of b2a2-positive or HLA-DRB1*0901-negative CML cell colonies increased when CML cells were cultured with b3a2-specific CD4+ CTL clones. These data suggest that bcr-abl-specific CD4+ CTLs recognize CML cells in an antigen-specific and HLA-DR-restricted manner, end that they do not inhibit, but in fact augment, CML cell growth.

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   出版者・発行元：BLACKWELL SCIENCE LTD  

We describe the first case of T-cell prolymphocytic leukaemia (T-PLL) in which the peripheral blood cells contained a human T-lymphotropic virus (HTLV) related tax sequence. Serum screening tests for anti-HTLV-I/II antibodies were negative. Polymerase chain reaction disclosed the presence of an HTLV-I tar sequence in the peripheral blood. Other sets of oligonucleotide primers for HTLV-I gag, pol, env and the long terminal repeat regions and for the HTLV-II pol region were negative in the DNA of the cells. Although patients with T-PLL have been reported to be seronegative for HTLV-I, our findings point to the possibility that HTLV-I infection might be involved in the aetiology of at least some cases of T-PLL and that there may be alternative mechanisms involved in HTLV-associated leukaemogenesis.

DOI： 10.1046/j.1365-2141.1998.00608.x

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   出版者・発行元：ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS  

The present study was undertaken to elucidate the mechanisms responsible for the cytotoxicity of herpes simplex virus (HSV)-specific CD4(+) human cytotoxic T lymphocyte (CTL) clones, focusing on perforin and membrane-bound lymphotoxin (LT) (tumor necrosis factor-p), Two HSV-specific CD4(+) CTL clones, which expressed both perforin and membrane-bound LT, exerted HSV-specific cytotoxicity and cytotoxicity against LT-sensitive L929 cells. These CD4(+) CTL clones lysed HSV-infected cells directly in an HLA class II-restricted manner and did not exhibit ''bystander killing.'' The culture supernatants of these clones stimulated with HSV antigen showed no cytotoxicity against HSV-infected cells or L929 cells, suggesting that adhesion to target cells is essential to their antigen-specific and antigen-nonspecific cytotoxicities. The cytotoxicities of these clones against HSV-infected autologous cells were inhibited by an anti-CD3 monoclonal antibody but not by an anti-LT antibody, Conversely, their cytotoxicities against L929 cells appeared to be partially inhibited by the anti-LT antibody but not by the anti-CD3 monoclonal antibody. Furthermore, target cell DNA fragmentation induced by these CD4(+) CTL clones was apparently observed in L929 cells but only faintly detected in HSV-infected autologous cells. L929 cell DNA fragmentation was also inhibited by adding the anti-LT antibody to CD4(+) CTL cultures, These data suggest that some CD4(+) CTL possess at least two cytolytic mediators, i.e., perforin and membrane-bound LT simultaneously, and can exert both antigen-specific and antigen-nonspecific cytotoxicity via two distinct mechanisms, necrosis and apoptosis. (C) 1996 Academic Press Inc.

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記述言語：英語   掲載種別：記事・総説・解説・論説等（学術雑誌）   出版者・発行元：AMER SOC MICROBIOLOGY  

In order to clarify antigenic variations among various isolates of human herpesvirus 6 (HHV-6) and cross-reactivity among HHV-6, HHV-7, and human cytomegalovirus (HCMV) in the T-cell immune response, the antigenic specificity of the proliferative response mediated by 232 CD4+ human T-cell clones directed against HHV-6, HHV-7, or HCMV was examined. The results obtained were as follows. (i) Although the majority of T-cell clones directed against HHV-6 proliferated in response to stimulation with all strains of HHV-6 used (U1102, Z29, SF, and HST), 7% (8 of 122) of the T-cell clones showed distinct patterns of proliferative response against strain U1102 (group A) and other strains of HHV-6 (group B). (ii) Of 99 T-cell clones, 71 showed a distinct proliferative response to HHV-6 and HHV-7, whereas 28 proliferated in response to stimulation with both HHV-6 and HHV-7. (iii) A small number of T-cell clones (9 of 232) showed cross-reactivity against HHV-6 and HCMV, and 2 of the 232 clones were reactive with HCMV as well as with HHV-6 and HHV-7. (iv) The specificity of gamma interferon production by T-cell clones following the stimulation with virus antigen was identical to that of their proliferative response. These data thus indicate the presence of antigenic variations among isolates of HHV-6 and also epitopes common to HHV-6 and HHV-7 and to HHV-6, HHV-7, and HCMV which are recognized by CD4+ T cells.

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