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DOI： 10.3925/jjtc1958.46.324

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Language：Japanese  

DOI： 10.3925/jjtc1958.46.1

CiNii Books

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

わが国での同種末梢血幹細胞移植(allo-PBSCT)の現状について全国調査を行った.年齢の中央値は37歳で,対象疾患はAML43例,CML19例,ALL14例,MDS14例,その他13例であった.ドナーはHLA適合同胞が85%を占めた.移植CD34陽性細胞数は,中央値5.3×10^6/kgで,血液学的回復は好中球500/μl以上の回復に中央値13日,血小板20,000/μl以上の回復に中央値13日であった.移植後100日以内の移植関連死亡は16.1%に見られた.急性GVHDは,II〜IV度が37.4%,III〜IVが16.2%に見られ,慢性GVHDは68.6%に見られた

DOI： 10.11406/rinketsu.40.1160

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Language：English   Publisher：STOCKTON PRESS  

CD56(+) angiocentric lymphoma has currently been recognized as a distinct clinical entity which is the prototype of the putative NK cell lymphomas, A 16-year-old Japanese girl with advanced CD56(+) angiocentric lymphoma received high-dose chemotherapy supported with syngeneic peripheral blood stem cell transplantation (PBSCT), Prior to syngeneic PBSCT, she received six cycles of conventional chemotherapy before transplantation, resulting in a partial response. PBSC were mobilized with granulocyte colony-stimulating factor (G-CSF) and collected from her identical twin, High-dose cyclophosphamide, MCNU, etoposide, and carboplatin were used for pretransplant conditioning. Syngeneic PBSCT was well tolerated. She achieved complete remission and is now surviving in continuous complete remission for more than 30 months after syngeneic PBSCT, Thus, marrow-ablative chemotherapy facilitated by autologous or allogeneic PBSCT should be considered as part of the primary therapy for poor prognosis NK cell lymphomas.

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Language：English   Publisher：BLACKWELL SCIENCE LTD  

Herpesviruses frequently cause serious complications after allogeneic bone marrow transplantation (allo-BMT). Recent studies have shown more rapid immune reconstitution after allogeneic peripheral blood stem cell transplantation (allo-PBSCT) compared with allo-BMT. However, it has not been clarified whether the improved immune reconstitution after allo-PBSCT is associated with a lower incidence of herpesvirus infections. We monitored the emergence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and HHV-7 DNA by a nested-double polymerase chain reaction in peripheral blood leucocytes from 22 allo-BMT and 16 allo-PBSCT patients, Each virus had an unique temporal profile of detection. HHV-6 DNA was detected most frequently at 3 weeks after transplantation, whereas CMV and EBV DNA were detected later (2-3 months). Detection rates of HHV-6 DNA at 3 and 4 weeks after allo-BMT were significantly higher than those after allo-PBSCT (9/16 v 2/13 at 3 weeks, P< 0.01; 10/21 v 1/15 at 4 weeks, P<0.01). Detection rates of the other three herpesviruses after the two types of allogeneic transplantation were not significantly different throughout observation period. Furthermore, detection of HHV-6 DNA within the first 4 weeks was associated with delayed platelet engraftment after both allo-BMT and allo-PBSCT (P<0.01). These results suggest an advantage for allo-PBSCT over allo-BMT in terms of suppression of HHV-6 reactivation and prevention of subsequent complications.

DOI： 10.1111/j.1365-2141.1999.01290.x

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Language：English   Publisher：CARDEN JENNINGS PUBL CO LTD  

Kininogens are multifunctional plasma glycoproteins. There are two forms of human kininogen: low molecular weight kininogen (LK) and high molecular weight kininogen (HK). Both are derived from the same gene by alternative splicing. Same patients with kininogen deficiency have been reported to be deficient only in HK while others are deficient in both HK and LK (total kininogen deficiency). We analyzed three Japanese patients with total kininogen deficiency by the Csp45I digestion study of exon 5 as previously reported in Williams trait and found that two had the same point mutation of C to T at base 22 of exon 5, resulting in a transition of CGA (Arg) codon to TGA (Stop) codon. This is the first report of molecular characterization of total kininogen deficiency in the Japanese population. (C) 1999 The Japanese Society of Hematology.

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Language：English   Publisher：CARDEN JENNINGS PUBL CO LTD  

We investigated the kinetics of posttransplant circulating progenitor cells (PTCPC) in the early phase after autologous (auto-) and allogeneic (allo-) peripheral blood stem cell transplantation (PBSCT). We analyzed the number of myeloid progenitor cells (CFU-GM) per 10 mi of peripheral blood (PB) on days 0 (just prior to transplantation), 1 (12-15 hours after completion of first transplantation), 2, 3, 5, 7, 10, 14, 17, 21 and 28 (after auto-PBSCT), and also additionally on day 35 after allo-PBSCT. A standard methylcellulose colony assay was used for analysing the number of CFU-GGM and BFU-E on all of the days. In addition, high proliferative potential-colony forming cells (HPP-CFC) of the harvested PBSC from donors and day 1 PB from recipients were assayed in 5 allo-PBSCT patients. Furthermore, a proportion of CD38(-) cells among CD34(+) cells in the harvested PBSC and day 1 PB was evaluated by two-color flow cytometric analysis in 5 allo-PBSCT patients. The number of CFU-GM on day 1 ranged from 7 to 119 per 10 mi PB after auto-PBSCT and from 15 to 61 per 10 mi PB after allo-PBSCT. After these transient increases, PTCPC diminished rapidly. Then, PTCPC emerged again on day 7 after auto-PBSCT and on day 10 or 14 after allo-PBSCT along with neutrophil recovery. A proportion of HPP-CFC among myeloid colonies from day 1 PB of recipients was significantly higher than that from the harvested PBSC from donors (65.6 +/- 12.7% vs. 17.4 +/- 13.0%, respectively n = 5, P = 0.0013). In addition, two-color how cytometric analysis revealed that the proportion of CD34(+)CD38(-) cells was significantly higher in day 1 PB of recipients than in the harvested PBSC from donors (57.5 +/- 17.6% vs. 11.7 +/- 4.9%, n = 5, P = 0.005). These observations suggest that both primitive and committed transplanted myeloid progenitor cells may circulate in the very early period following PBSCT. (C) 1999 The Japanese Society of Hematology.

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DOI： 10.11406/rinketsu.40.1160

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DOI： 10.11406/rinketsu.40.1051

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DOI： 10.11406/rinketsu.40.1051

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Language：Japanese   Publisher：一般社団法人 日本血液学会  

DOI： 10.11406/rinketsu.40.451

PubMed

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/1999263703

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Language：English   Publisher：BLACKWELL SCIENCE LTD  

A patient with non-Hodgkin's lymphoma who received a CD34-selected autologous peripheral blood stem cell transplant (PBSCT) developed cytomegalovirus retinitis, adenovirus-associated haemorrhagic cystitis (HC) and fatal herpes simplex virus pneumonia. Depletion of mature T cells from the graft and a persistent decrease in CD4(+) lymphocytes following PBSCT may have predisposed this patient to such viral infections. Infusion of cryopreserved autologous PBSC (containing mature T cells) was effective for adenovirus-associated HC. Immunosuppression and resultant viral infections may affect patients receiving CD34-selected autologous transplantation.

DOI： 10.1046/j.1365-2141.1998.00572.x

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DOI： 10.1016/S0925-5710(98)00045-0

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Language：English   Publisher：STOCKTON PRESS  

The safety and efficacy of myeloablative therapy followed by autologous peripheral blood stern cell transplantation (ABSCT) for acute myelogenous leukemia (AML) were evaluated in 60 patients, Peripheral blood stem cells (PBSC) were collected during recovery after consolidation chemotherapy, High-dose chemotherapy consisting of busulfan (16 mg/kg), etoposide (40 mg/kg), and cytosine arabinoside (3 g/m(2) x 4) (BEA regimen) was used for pretransplant conditioning in 13 patients, For the remaining 47 patients, granulocyte colony-stimulating factor (G-CSF) was administered concurrently with the BEA regimen during conditioning, Unpurged, cryopreserved PBSC containing a median number of 5.4 x 10(8) MNC/kg or 12 x 10(4) CFU-GM/kg were reinfused at transplantation. The median number of days to granulocytes exceeding 500/mu l and last platelet transfusion were 15 (8-44) and 24 (0->180), respectively, The 3-year probabilities of disease-free survival (DFS) and relapse were 78.6 and 21.4% for patients transplanted in first remission, 29.6 and 64.4% for those in second or third remission, and 11.1 and 77.8% for those in relapse, respectively, There were no transplant-related deaths within 100 days of transplantation, Age, disease status at transplantation, and number of induction chemotherapies to first complete remission were risk factors affecting the outcome of ABSCT, These results of ABSCT for AML in first remission warrant a prospective study of ABSCT as post-remission therapy.

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Language：English   Publisher：STOCKTON PRESS  

Cytomegalovirus (CMV) infection and CMV-associated disease were monitored using the CMV antigenemia assay in 72 patients who received allogeneic bone marrow transplantation (BMT), and their incidences were compared between related and unrelated donor transplant patients, The incidence of CMV infection after BMT was significantly higher in patients who received transplants from HLA-matched unrelated donors than from HLA-matched sibling donors (87% vs 53%, P < 0.05), CMV-associated disease developed in 73% of unrelated and in 14% of sibling donor transplant patients (P < 0.01), The peak levels of CMV antigenemia were significantly higher in unrelated donors than in sibling donor transplant patients (16 vs 1 CMV antigen-positive cells per 50000 WBCs, P < 0.01), The median number of CMV antigen-positive cells on first detection was also significantly higher in unrelated donor transplant patients (15 vs 1, P < 0.01), The detection of CMV antigen-positive cells preceded the development of CMV-associated disease in 18% of unrelated donor transplant patients, suggesting a lower predictive value of CMV antigenemia for subsequent CMV-associated disease in unrelated donor BMT, Careful monitoring and further studies are needed for the early diagnosis and prevention of CMV-associated disease in unrelated donor BMT.

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DOI： 10.11406/rinketsu.38.142

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Language：Japanese  

DOI： 10.11406/rinketsu.38.578

PubMed

CiNii Books

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DOI： 10.11406/rinketsu.38.578

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Language：Japanese  

DOI： 10.11406/rinketsu.38.142

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Language：English   Publisher：HARWOOD ACAD PUBL GMBH  

We investigated the expression of an apoptosis associated antigen (Fas) (CD95) on hematopoietic progenitor cells. Freshly isolated CD34(+) cells from bone marrow did not express Fas. However, interferon-gamma (IFN-gamma) and/or tumor necrosis factor-a (TNF-alpha) induced dose-dependent expression of both Fas mRNA and Fas protein on the surface of CD34(+) cells after 48 hours of serum-free culture. TNF-alpha-induced Fas expression was mediated by p55-TNF-alpha receptor. Induced Fas was functional as it could transduce apoptotic signals in response to anti-Fas monoclonal antibody (MoAb).
The Fas-defective 1pr mice are reported to have abnormally radio-resistant hematopoietic stem cells. Consequently, we also investigated the relation between Fas and ionizing radiation. Human CD34(+) cells expressed Fas following low-dose ionizing radiation in a dose-dependent fashion. Fas induced on CD34(+) cells mediated apoptosis in response to anti-Fas MoAb. We, evaluated the expression of Fas and Bcl-2 on CD34(+) hematopoietic progenitor cells expanded in vitro. CD34(+) cells isolated from bone marrow were cultured with hematopoietic growth factors for 7 days. Approximately half of the freshly isolated CD34(+) cells expressed Bcl-2. CD34(+) cells cultured with hematopoietic growth factors,gradually became positive for Fas and rapidly lost Bcl-2 expression. Furthermore, apoptosis was induced in the cultured CD34(+) population in response to anti-Fas MoAb. Thus, functional Fas can be induced on hematopoietic progenitor cells in vitro by negative hematopoietic regulators, ionizing radiation, as well as positive hematopoietic regulators. The Fas system is thought to play an important role at the level of hematopoietic progenitor cells in both physiologic and pathologic conditions.

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Language：English   Publisher：W B SAUNDERS CO  

Fas antigen (Fas Ag; CD95) is a cell surface molecule that can mediate apoptosis. Bcl-2 is a cytoplasmic molecule that prolongs cellular survival by inhibiting apoptosis. To investigate the role of both molecules in hematopoiesis, we evaluated the expression of Fas Ag and Bcl-2 on CD34(+) hematopoietic progenitor cells expanded in vitro. CD34(+) cells isolated from bone marrow were cultured in Iscove's modified Dulbecco's medium supplemented with 10% fetal calf serum, 1% bovine serum albumin, 50 ng/mL stem cell factor, 50 ng/mL interleukin-3 (IL-3), 50 ng/mL IL-6, 100 ng/mL granulocyte colony-stimulating factor, and 3 U/mL erythropoietin for 7 days. Colony-forming unit of granulocytes/macrophages (CFU-GM) and burst-forming unit of erythroids (BFU-E) were expanded 6.9-fold and 8.8-fold in number at day 5 of culture, respectively. Freshly isolated CD34(+) cells did not express Fas Ag, whereas approximately half of them expressed Bcl-2. CD34(+) cells cultured with hematopoietic growth factors gradually became positive for Fas Ag and rapidly lost Bcl-2 expression. Furthermore, apoptosis was induced in the cultured CD34(+) population when anti-Fas antibody (IgM; 1 mu g/mL) was added, as shown by significant decrease in the number of viable cells, morphologic changes, induction of DNA fragmentation, and significant decrease in the number of clonogenic progenitor cells including CFU-GM and BFU-E. These results indicate that functional expression of Fas Ag is induced on CD34(+) cells expanded in vitro in the presence of hematopoietic growth factors. Induction of Fas Ag and downregulation of Bcl-2 may be expressed as part of the differentiation program of hematopoietic cells and may be involved in the regulation of hematopoiesis. (C) 1996 by The American Society of Hematology.

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Language：English   Publisher：W B SAUNDERS CO  

The leukemia-specific AML1/ETO fusion gene has been shown to be detected by reverse transcriptase polymerase chain reaction (RT-PCR) analysis in patients with t(8;21) acute myelogenous leukemia (AML) in long-term remission. In the present study, the AML1/ETO mRNA could be detected by RT-PCR in bone marrow (BM) and/or peripheral blood (PB) samples from all 18 patients who had been maintaining complete remission for 12 to 150 months (median, 45 months) following chemotherapy or PB stem cell transplantation (PBSCT), whereas it could not be detected in four patients who had been maintaining remission for more than 30 months following allogeneic BM transplantation (BMT). We surveyed the expression of AML1/ETO mRNA in clonogenic progenitors from BM in these cases. Notably, 51 of 2.469 colonies from clonogenic progenitors (2.1%) expressed the AML1/ETO mRNA in 18 cases who were RT-PCR(+) in BM and/or PB samples. Expression was observed in various clonogenic progenitors, including granulocyte-macrophage colonies, mixed colonies, erythroid colonies, and megakaryocyte colonies. Furthermore, we analyzed the clonality of these progenitors by X-chromosome inactivation patterns of the phosphoglycerate kinase (PGK) gene in four female patients. The AML1/ETO mRNA(+) progenitors showed the PGK allele identical to that detected in the leukemic blasts from the time of initial diagnosis. Normal constitutive hematopoiesis was sustained by polyclonal BM reconstitution in these patients. Accordingly, these committed progenitor cells that express AML1/ETO mRNA during remission likely have arisen from common t(8;21)(+) pluripotent progenitor cells with at least trilineage differentiation potential. These data strongly suggest that the origin of the clonogenic leukemic progenitors of t(8;21) AML may be multipotent hematopoietic progenitors that acquired the t(8;21) chromosomal abnormality. (C) 1996 by The American Society of Hematology.

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Language：English   Publisher：JAPAN SOC INTERNAL MEDICINE  

We report an unusual case of cytomegalovirus (CMV) interstitial pneumonitis (IP) occurring in a 51-year-old Japanese woman with systemic lupus erythematosus (SLE). She developed hypoxemia after intensive immunosuppressive therapy with prednisolone and cyclophosphamide, Fine crackles were audible in the lower lungs bilaterally, Chest X-ray and computed tomography confirmed the presence of IP. CMV-antigenemia was confirmed by immunological staining of leukocytes using the peroxidase-labeled monoclonal antibody, HRP-C7. Hypoxemia improved gradually on methylprednisolone pulse therapy and gancyclovir, and CMV-antigen positive leukocytes disappeared from the peripheral blood, Data suggest the importance of CMV as a cause of IP in SLE, and the usefulness of the assay for CMV-antigenemia with C7-HRP for rapid diagnosis.

DOI： 10.2169/internalmedicine.35.517

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Language：English   Publisher：BLACKWELL SCIENCE LTD  

We studied the generation of human natural killer (NK) cells from CD34(+) cells that were isolated from peripheral blood stem cells (PBSC) mobilized by granulocyte colony-stimulating factor (G-CSF). The isolated CD34(+) cells were cultured in the presence of a combination of interleukin-1 (IL-1 alpha), IL-2, and stem cell factor for 5 weeks without marrow stroma. We found that the CD34(+) cells isolated from G-CSF-mobilized PBSC (G-CSF/PBSC) could differentiate into a population of NK cells which were CD56(+(bright))/CD3(-) and showed morphologic characteristics of large granular lymphocytes. Immunophenotypic analysis of the NK cells thus generated showed that a small proportion of them expressed CD2, CD8 and CD16 surface markers and approximately half of them coexpressed CD7. This NK population exhibited cytotoxic activity against a NK-sensitive cell line, K562. These observations suggest that CD34(+) cells from G-CSF/PBSC contain precursors of NK cells that can differentiate into functional NK cells.

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DOI： 10.11406/rinketsu.37.358

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DOI： 10.11406/rinketsu.37.358

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Language：English   Publisher：BLACKWELL SCIENCE LTD  

Peripheral blood stem cells (PBSC) have been used increasingly for haemopoietic reconstitution after marrow-ablative chemotherapy in patients with acute leukaemia because of the possibility that there is a lower risk of leukaemic contamination, We have developed a titration assay using a competitive reverse transcriptase polymerase chain reaction (RT-PCR) which is able to estimate the number of AML1/ETO transcripts so that minimal residual disease (MRD) can be monitored quantitatively in patients with t(8;21) acute myelogenous leukaemia (AML). Using a qualitative RT-PCR method, AML1/ETO transcripts could be detected in all samples from 15 first PBSC harvests and 11 second PBSC harvests obtained from 15 patients with t(8;21) AML, With our competitive RT-PCR assay, the number of AML1/ETO transcripts was found to be lower in the second PBSC harvest than that in the first in every individual, Furthermore, MRD in PBSC harvests was less than that in the corresponding bone marrow obtained on the day of PBSC collection in the individual patients studied. In 10 patients who received autologous blood stem cell transplantation (ABSCT), we could not find a relationship between the number of AML1/ETO transcripts in the infused PBSC harvests and the clinical outcome after ABSCT. The present: study clearly indicates that although PBSC harvests collected after consolidation chemotherapy are contaminated by leukaemic cells, the degree of leukaemic contamination may decrease as chemotherapy is repeated, The mobilization of PBSC by repeated chemotherapy may provide an advantageous source of haemopoietic stem cells for ABSCT.

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Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：W B SAUNDERS CO  

We investigated the expression of an apoptosis-associated antigen (Fas) (CD95) on hematopoietic progenitor cells in the presence or absence of interferon-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha). CD34(+) cells freshly isolated from bone marrow did not express Fas. However, IFN-gamma and/or TNF-alpha induced the expression of both the mRNA of Fas and Fas itself in a dose-dependent fashion on the surface of CD34(+) cells after 48 hours of serum-free culture, IFN-gamma and TNF-alpha had a synergistic effect on the induction of Fas, when both cytokines were added to the culture. The TNF-alpha-induced Fas expression is mediated by p55 TNF-alpha receptor, CD34(+) cells cultured in medium alone or with stem cell factor (SCF) showed some slight expression of Fas. When anti-fas antibody (IgM) was added to CD34(+) cells after the induction of Fas expression, CD34(+) cells underwent apoptosis, as shown by a decrease in the number of viable cells, morphologic changes, the induction of DNA fragmentation, and a decrease in the number of colony-forming cells (CFC) including colony-forming unit granulocytes/macrophages (CFU-GM) and burst-forming unit erythroids (BFU-E). These observations indicate that IFN-gamma and/or TNF-alpha, well known as negative hematopoietic regulators, induce functional Fas on hematopoietic progenitor cells. The suppression of hematopoiesis by negative hematopoietic regulators may be mediated in part by Fas induction.
(C) 1995 by The American Society of Hematology.

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Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

We present a 32-year-old-woman with Cushing's disease and sarcoidosis, She had been diagnosed as having Cushing's disease in 1985, She had transsphenoidal surgery followed by pituitary radiation, Subsequently her plasma cortisol level gradually decreased to normal range, In 1991, she manifested bilateral hilar lymphadenopathy on chest X-ray, erythema nodosum, subcutaneous nodules and granulomatous uveitis, From the histological findings of the skin lesions, the patient was diagnosed as having sarcoidosis, Interestingly, an inverse relationship between the disease activity of sarcoidosis and the level of serum cortisol in Cushing's disease was observed in the clinical course of this patient. Co-existence of Cushing's disease and sarcoidosis is very rare. Since the therapeutic significance of steroids in sarcoidosis has been well established, this case provides insight to the relationship between sarcoidosis and steroids.

DOI： 10.2169/internalmedicine.34.580

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Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：BLACKWELL SCIENCE LTD  

We investigated the biological characteristics of 'eosinophilic' leukaemic blasts from a patient with eosinophilic blast crisis of chronic myelogenous leukaemia (CML). Southern blot analysis of the bcr gene demonstrated the identical single rearranged band in both the leukaemic blasts and mature eosinophils, IL-3, IL-5 and GMA-CSF significantly enhanced proliferation and differentiation of these leukaemic blasts, and only eosinophils were generated from in vitro cultures. Those eosinophils expressed the B3A2 chimaeric messenger RNA seen in the leukaemic blasts. These observations indicate that eosinophil progenitors may be involved in the development of eosinophilic blast crisis of CML and that IL-3, IL-5 and GM-CSF act on the leukaemic eosinophil progenitors.

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Language：Japanese   Publisher：The Japan Endocrine Society  

A-26-year-old female was admitted to our hospital on December 4, 1992, because of recurrent fever. She had experienced recurrent fever of over 38°C, occurring at irregular intervals 4-6 times a year with chest or abdominal pain, since the age of 19. After delivery of a baby at the age of 25, her symptoms had increased to once a week. In the febrile phase, leukocytosis, an increased erythrocyte sedimentation rate and positive CRP were recognized. These symptoms and laboratory findings spontaneously disappeared within a few days. Despite systemic and careful examinations, no evidence of infectious diseases, collagen diseases or malignant diseases were found. There were no significant differences of serum and urine catecholamines, and urine etiocholanolone between the febrile phase and the afebrile phase. An intravenous infusion of metaraminol induced symptoms similar to a spontaneous attack, and the metaraminol rechallenge test became negative after she was treated with oral colchicine. Based on these findings, she was diagnosed as having familial Mediterranean fever. Since she was treated with colchicine, the febrile attacks have decreased. Significantly, her elder brother has had similar recurrent fever with abdominal pain. He was diagnosed as having familial Mediterranean fever due to a positive metaraminol provocative test, and his febrile attacks have also been suppressed by colchicine.<BR>This is the first case of familial Mediterranean fever with obvious family history in Japan.

DOI： 10.1507/endocrine1927.70.10_1075

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Other Link： http://search.jamas.or.jp/link/ui/1995245549

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Language：Japanese  

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