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S Shiobara

Publications and source records attributed to S Shiobara.

At least 55 records · Page 3Linked to original sources
PubMed1992

Interferon-gamma gene expression in unstimulated bone marrow mononuclear cells predicts a good response to cyclosporine therapy in aplastic anemia.

Cyclosporine (CyA) therapy has been shown to be effective in some patients with aplastic anemia. In an attempt to characterize aplastic patients likely to benefit from CyA therapy, we examined bone marrow mononuclear cells (BMMC) obtained before therapy from 23 patients with aplastic anemia, who were treated with CyA alone. Expression of four myelosuppressive cytokines, including tumor necrosis factor (TNF), lymphotoxin, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and interferon-gamma (IFN-gamma) was examined using polymerase chain reaction (PCR)-assisted messenger RNA (mRNA) amplification. mRNA for TNF, lymphotoxin, and MIP-1 alpha was readily detectable at variable levels in BMMC from normal and transfused controls as well as in BMMC from aplastic patients. In contrast, IFN-gamma mRNA was only demonstrable in BMMC from some patients with aplastic anemia, irrespective of a history of transfusions. Of 13 patients who responded to CyA therapy and achieved transfusion-independence, IFN-gamma mRNA was detected in 12 patients, whereas the mRNA was only detectable in 3 of 10 patients refractory to CyA therapy (P = .003, Fisher's exact test). Follow-up examination of BMMC obtained from seven CyA-responding patients after hematologic remission showed disappearance of IFN-gamma mRNA in four patients. These results suggest that detection of IFN-gamma gene expression in pretreatment BMMC from aplastic patients using PCR may be helpful in predicting a good response to CyA therapy.

Adolescent↗
PubMed1992

Demonstration of Ph1-negative host haemopoietic progenitor cells in an allogeneic marrow transplant recipient with chronic myelocytic leukaemia using polymerase chain reaction.

In an attempt to characterize host-derived haemopoietic cells in mixed haemopoietic chimeras, we studied bone marrow cells from male patients with chronic myelocytic leukaemia (CML) transplanted with marrow grafts from female donors. Amplification of a Y chromosome-specific sequence (YDNA) in DNA from marrow mononuclear cells using polymerase chain reaction (PCR) revealed persistence of host cells in 2 of 3 patients studied. On the other hand, persistence of Ph1-positive cells was unable to be demonstrated in the marrow cells from these patients using reverse transcription PCR (RT-PCR) for detecting bcr-abl chimeric messenger RNA. RT-PCR sensitivity for detecting minimal Ph1-positive cells in a background of Ph1-negative cells proved better than that of the PCR for detecting male cells among female cells. When bone marrow progenitor cells from one of the documented mixed chimeras were analyzed after an in vitro colony assay using PCR, 2 of 12 erythroid burst-forming units (BFU-E) proved to be YDNA-positive, i.e., of host origin, whereas none of them was shown to be Ph1-positive, although 12 BFU-E analyzed in the marrow cells obtained pretransplant from the same patient were all YDNA- and Ph1-positive. These findings indicate that, in some marrow transplant recipients with CML, a small number of host-derived normal haemopoietic progenitor cells may persist following lethal chemoradiotherapy and allogeneic bone marrow transplantation despite the fact that Ph1-positive clones can be eradicated.

Adult↗
PubMed1992

[An autopsy case of dermatomyositis associated with interstitial pneumonia probably due to cytomegalovirus infection].

An autopsy case of dermatomyositis (DM) associated with interstitial pneumonia probably due to cytomegalovirus infection is reported. After corticosteroid therapy for 1 month, a 79-year-old man with DM developed acute respiratory failure due to interstitial pneumonia and died in spite of intensive respiratory care. By polymerase chain reaction method (PCR), DNA of cytomegalovirus (CMV) was detected in the bronchoalveolar lavage fluid (BALF). CMV was also detected by the method of conventional virus culture from BALF. These findings suggested that initial infection or reactivation of CMV had occurred in the lungs. The autopsy specimen revealed the findings of interstitial pneumonia compatible with CMV pneumonitis, but without the presence of intranuclear inclusion bodies. Although the present case of interstitial pneumonia should not strictly be diagnosed as definite CMV pneumonitis without the presence of intranuclear inclusion bodies in the lung tissue, initial infection or reactivation of CMV in the lungs may have contributed to the pathogenesis of interstitial pneumonia. In other cases of collagen vascular disease associated with interstitial pneumonia, CMV or other viruses may contribute to the pathogenesis of interstitial pneumonia.

Aged↗
PubMed1992

Analysis of late graft failure after allogeneic bone marrow transplantation: detection of residual host cells using amplification of variable number of tandem repeats loci.

In an attempt to gain insight into the etiology of late graft failure, we analysed the origin of bone marrow mononuclear cells (BMMC) and peripheral blood leukocytes in patients with this syndrome by taking advantage of DNA fragment length polymorphisms in variable number of tandem repeats (VNTR) loci. Amplification of the VNTR loci in DNA from BMMC using the polymerase chain reaction revealed the persistence of host cells in two of four patients studied. One of the patients, whose cultured lymphocytes inhibited in vitro growth of donor-derived hemopoietic progenitor cells, responded to immunosuppressive therapy and donor-derived hemopoiesis was restored. In the other patient, host-derived polymorphonuclear leukocytes (PMN) appeared together with donor-derived PMN from the early post-transplant period, and he proceeded to relapse with myelodysplastic syndrome. In the other two patients in whom host cells were not detectable, the marrow hypoplasia was associated with chronic graft-versus-host disease (GVHD). The hypoplasia improved significantly as the chronic GVHD improved in response to immunosuppressive therapy. We conclude that detecting minimal residual host cells by means of amplification of VNTR loci is valuable for understanding the etiology of late graft failure in marrow transplant recipients, and could prove helpful for choosing appropriate therapy for this syndrome.

Adolescent↗
PubMed1991

Origin of hematopoietic progenitor cells after bone marrow transplantation: analysis by means of a Y-chromosome specific DNA probe.

To characterize hematopoietic cells in mixed hematopoietic chimeras after allogeneic bone marrow transplantation (BMT), the authors examined the origin of progenies derived from hematopoietic progenitor cells of male recipients who received a marrow graft from female donors, by use of a Y-chromosome specific DNA (YDNA) probe in combination with an in vitro colony assay. Host-type hematopoietic cells were detected in cultured bone marrow mononuclear cells (BMMC) from 4 out of 6 patients studied, who were all in complete remission. In 2 patients of the mixed chimeras, the relative amount of host-derived YDNA from BMMC increased after methylcellulose cultures for 14 days. Analysis of individual colonies derived from granulocyte-macrophage colony forming units (CFU-GM) from these mixed chimeras, including 2 patients with chronic myelogenous leukemia (CML), revealed approximately 30% of total colonies were host-type, although no evidence for the existence of residual Ph1 positive cells was obtained by using polymerase chain reaction for detecting bcr-abl chimeric messenger RNA in the 2 CML patients. These findings provide direct evidence that considerable numbers of host-derived normal hematopoietic progenitors survive and persist for a long term in a certain population of marrow recipients, after BMT following supralethal radiochemotherapy.

Bone Marrow Transplantation↗
PubMed1991

[Indication of bone marrow transplantation for acute leukemia in first remission].

We presented the results of Kanazawa experience and suggested integrative approach for treatment of acute leukemia in first remission. From 1977 to 1990, 23 patients with acute leukemia (AL) in first remission (ALL 13; ANL 10) were received marrow transplantation from HLA matched donor (allogeneic 22, syngeneic 1) after conditioning with CY + TBI (17), BU + CY (5) or AraC + BU + CY (1). Probability of 5 year survival in all AL patients is 52% (ALL 69%, ANL 30%). Relapse rate in all AL is 22% (ALL 38%, ANL 0%). The results of high risk ALL is superior to alternative approach of initial chemotherapy plus transplantation in subsequent remission. In addition, after 1987, there is no fatal cases within 100 days after transplantation. From current status of marrow transplantation and chemotherapy, together with our experience, we recommended initial allogeneic BMT for ANL and high risk adult ALL in first remission. BMT from unrelated matched donor or autologous marrow should be considered next. For high risk child ALL and low risk adult ALL, initial allogeneic BMT should be considered if related matched donor is available.

Acute Disease↗
PubMed1990

Transient engraftment of syngeneic bone marrow after conditioning with high-dose cyclophosphamide and thoracoabdominal irradiation in a patient with aplastic anemia.

We describe the clinical course of a 16 year old girl with aplastic anemia who was treated by syngeneic bone marrow transplantation. Engraftment was not obtained by simple infusion of bone marrow without immunosuppression. The patient received a high-dose cyclophosphamide and thoracoabdominal irradiation, followed by second marrow transplantation from the same donor. Incomplete but significant hematologic recovery was observed; however, marrow failure recurred 5 months after transplantation. Since donor and recipient pairs were genotypically identical, graft failure could not be attributed to immunological reactivity of recipient cells to donor non-HLA antigens. This case report implies that graft failure in some cases of aplastic anemia might be mediated by inhibitory cells resistant to cyclophosphamide and irradiation.

Abdomen↗
PubMed1990

[Cyclosporin therapy for aplastic anemia].

We treated 14 patients with aplastic anemia (6 severe, 8 moderate) who did not respond to high dose methylprednisolone, antilymphocyte globulin, or anabolic steroid with cyclosporin (CyA) for more than 4 weeks. Four of them (29%) showed clinical improvement to transfusion-independence. The response rate of patients who received CyA more than 5 weeks was 50% (4 out of 8). The dose of CyA given to the 4 patients who improved after the therapy was 5 to 9 mg/kg/day. One patient needed 11 weeks until the first sign of response (increase of reticulocytes) appeared. In the other three patients, platelets increased first in response to CyA within 5 weeks. Side effects such as hypertricosis and gingival hyperplasia were frequently seen during the CyA therapy, but since they were not so severe or transient, almost all patients tolerated the therapy. These results indicate that CyA can be an efficacious drug for patients with refractory aplastic anemia. Long term treatment with a relatively low dose of CyA may be important for obtaining a high response rate.

Adolescent↗