Biomedical subjects
Publications and source records attributed to M Hino.
We describe a 20-year-old woman with trisomy 18 mosaicism, who presented with skeletal anomalies, epilepsy, mental retardation, and linear and whorled naevoid hypermelanosis.
A 71-year-old Japanese male with myelodysplastic syndrome progressing to overt leukaemia and hepatocellular carcinoma developed dyspnea and urticaria immediately after infusion of platelet concentrate (PC). He exhibited an identical reaction following blood transfusion. Serum haptoglobin was undetectable. The patient was determined to be homozygous for Hp(del) by polymerase chain reaction (PCR). Antibody to haptoglobin was detected by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. No antibodies against human leucocyte antigen (HLA) or platelet-specific antigens were detected. Washed PC and washed red blood cells were effective in preventing the transfusion-related anaphylactoid reactions.
Rhabdomyolysis is an unusual complication of hematopoietic stem cell transplantation (HSCT). Cyclophosphamide has been one of the key drugs in the most common preparative regimen for HSCT. We present here a rare case of acute rhabdomyolysis following administration of high-dose cyclophosphamide. A 47-year-old woman with adult T-cell leukemia in remission was treated with high-dose cyclophosphamide as a preparative regimen for allogeneic bone marrow transplantation. Nineteen hours later, general convulsions and acidosis suddenly occurred. Levels of serum creatine kinase (skeletal muscle type), myoglobin, and aldolase were markedly elevated to 32870 IU/l, 640 ng/ml, and 240.3 IU/l, respectively. Rhabdomyolysis caused by high-dose cyclophosphamide was diagnosed, and the preparative chemotherapy was discontinued. Subsequently, her muscular signs and symptoms improved, and the results of laboratory examinations returned to normal after 2 weeks. She had previously been treated with conventional doses of cyclophosphamide, doxorubicin, vincristine, and prednisolone without evidence of rhabdomyolysis. Acute rhabdomyolysis may be an adverse effect specific to high-dose cyclophosphamide therapy.
We investigated activation of mitogen-activated protein kinase (MAPK) subtype cascades in human neutrophils stimulated by IL-1beta. IL-1beta induced phosphorylation and activation of p38 MAPK and phosphorylation of MAPK kinase-3/6 (MKK3/6). Maximal activation of p38 MAPK was obtained by stimulation of cells with 300 U/ml IL-1beta for 10 min. Extracellular signal-regulated kinase (ERK) was faintly phosphorylated and c-Jun N-terminal kinase (JNK) was not phosphorylated by IL-1beta. IL-1beta primed neutrophils for enhanced release of superoxide (O(2)(-)) stimulated by FMLP in parallel with increased phosphorylation of p38 MAPK. IL-1beta also induced O(2)(-) release and up-regulation of CD11b and CD15, and both responses were inhibited by SB203580 (p38 MAPK inhibitor), suggesting that p38 MAPK activation mediates IL-1beta-induced O(2)(-) release and up-regulation of CD11b and CD15. Combined stimulation of neutrophils with IL-1beta and G-CSF, a selective activator of the ERK cascade, resulted in the additive effects when the priming effect and phosphorylation of p38 MAPK and ERK were assessed. IL-1beta induced phosphorylation of ERK and JNK as well as p38 MAPK in human endothelial cells. These findings suggest that 1) in human neutrophils the MKK3/6-p38 MAPK cascade is selectively activated by IL-1beta and activation of this cascade mediates IL-1beta-induced O(2)(-) release and up-regulation of CD11b and CD15, and 2) the IL-1R-p38 MAPK pathway and the G-CSF receptor-ERK pathway work independently for activation of neutrophils.
A 79-year-old Japanese man was admitted to our hospital with dyspnea in June 1999. Physical examination revealed general exanthema, hepatosplenomegaly, and lymphadenopathy. Increased numbers of abnormal cells were observed in peripheral blood; these cells were of lymphoblastic morphology with high nuclear/cytoplasm ratios and few azurophilic granules. Immunophenotypic analysis revealed positivity for CD2, CD4, CD56, and HLA-DR, and negativity for CD3, CD13, CD16, CD33, CD34, and T cell receptor (TCR). On genotypic analysis, TCRgamma chain was rearranged, but neither the TCRbeta chain nor TCRdelta chain. Despite an initial good response to chemotherapy the disease relapsed in the early stage, and the patient died 6 months after diagnosis.
The synthesis and biological properties of a novel water-soluble echinocandin-like lipopeptide, FR131535, are described. This compound displayed potent in vitro and in vivo antifungal activities. The hemolytic activity of FR901379 was reduced by replacing the acyl side chain. This compound showed good water-solubility, comparable to the natural product FR901379.
Transcript levels of hexokinase (HK) isozymes and glucose transporter (GLUT) isoforms in RNA samples of AH130 cells obtained from dish cultures and ascites were evaluated in a quantitative manner. In AH130 cells cultured in dishes, HKI and HKII were expressed at a similar level, but HKIII and HKIV were not. GLUT1 and GLUT3 were also expressed, and messages of these two isoforms represented 27% and 71%, respectively, of the total GLUT messages. A faint signal of GLUT2 was also observed. On the contrary, in cells grown as ascites, the transcript of HKII was dominant, and its level was about 15-fold over that of dish-cultured AH130 cells. Transcript levels of GLUT1 and GLUT3 were 4.5- and 2-fold, respectively, higher than those in dish-cultured cells. Thus, GLUT1 was more susceptible to changes in culture conditions than GLUT3. Based on these results, we concluded that the change in growth conditions caused synchronized changes in the transcript levels of HKII and GLUT1 in AH130 cells. However, such marked changes in the transcript levels of HKII and GLUT1 were not observed when AH130 cells were cultured in dishes under a hypoxic condition, indicating that the observed changes were not solely attributable to the difference in oxygen concentration between the ascites and cell culture conditions. Accordingly, other factors such as growth factors may be responsible for this difference in levels of HKII and GLUT1 between the two growth conditions.
Extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) are major signaling molecules activated in human neutrophils stimulated by cytokines. Both molecules were cleaved at the N-terminal portion in neutrophils undergoing apoptosis induced by in vitro culture alone or treatment with TNF and/or cycloheximide. The cleavage of both molecules was inhibited by G-CSF and benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, a caspase inhibitor, both of which can inhibit neutrophil apoptosis. In a cell-free system, ERK and p38 MAPK were not cleaved by recombinant caspase-3 or caspase-8 while gelsolin was cleaved by caspase-3 under the same condition. The cleavage of both molecules appears to be specific to mature neutrophils, since it was not detected in immature cells (HL-60 and Jurkat) undergoing apoptosis, indicating that proteases responsible for the cleavage of both molecules may develop during differentiation into mature neutrophils. Concomitant with the cleavage of ERK and p38 MAPK, GM-CSF- and TNF-induced superoxide release, adherence, and phosphorylation of ERK and p38 MAPK were decreased in neutrophils undergoing apoptosis. In addition, GM-CSF- and TNF-induced superoxide release and adherence were inhibited by PD98059 MAPK/ERK kinase inhibitor) as well as SB203580 (p38 MAPK inhibitor), suggesting possible involvement of ERK and p38 MAPK in superoxide release and adherence induced by these cytokines. These findings indicate that ERK and p38 MAPK are cleaved and degraded in neutrophils undergoing apoptosis in a caspase-dependent manner and the cleavage of both molecules may be partly responsible for decreased functional responsiveness to inflammatory cytokines.
A 26-year-old woman with idiopathic thrombocytopenic purpura (ITP) was admitted to our hospital because of fever and rash. Blood tests revealed thrombocytopenia, liver dysfunction, coagulopathy, and hyperferritinemia. Bone marrow examination revealed many atypical lymphocytes and some histiocytes with hemophagocytosis. On admission she was diagnosed with rubella virus-associated hemophagocytic syndrome (VHAS), but on laboratory examination, she was seropositive for varicella-zoster virus (VZV)-IgM as well as rubella virus-IgM. She was therefore diagnosed with dual infection by rubella virus and VZV. Her simultaneous rubella virus and VZV infection may have been related to the VAHS pathogenesis. She was treated with prednisolone and gamma globulin therapy and recovered completely.
A 64-year-old woman with adult T cell leukemia (ATL) was admitted to our hospital with severe hypercalcemia. The serum calcium level was elevated to 14.9 mg/dl. Biochemical parameters for bone formation including serum osteocalcin (bone Gla protein, BGP) and alkaline phosphatase (ALP) were normal. The serum levels of tartrate-resistant acid phosphatase (TRAP), a parameter for bone resorption, were increased (4.6 KAU). The serum level of parathyroid hormone-related protein (PTHrP) was elevated (343 pmol/l). The cytokines with stimulatory effects on bone resorption, such as interleukin (IL)-1alpha, IL-1beta, IL-6, and tumor necrosis factor-alpha, were not detected. Serum Ca levels, PTHrP levels, and TRAP levels decreased with the decrease in ATL cells after chemotherapy, while serum BGP levels and ALP levels increased. On the 29th hospital day, ATL cells began to increase again. Then serum PTHrP levels, Ca levels, and TRAP levels increased, while serum BGP levels and ALP levels decreased. A marked excessive bone resorption with suppressed bone formation (uncoupling) occurred in this patient. The ATL cells produced not only PTHrP but also IL-1alpha and IL-1beta. These results suggest that PTHrP may act as a humoral factor and IL-1 may act as a local factor in bone metabolism of ATL patients.
In the course of screening for antifungal antibiotics, we have discovered a novel series of lipopeptide compounds structurally related to, but highly superior to, echinocandin B in terms of their water solubility due to the presence of a sulfate residue. These compounds, WF11899s, WF738s, WF14573s, WF16616 and WF22210, and their derivatives have diversity in their nuclear structures and acyl side chains. The producing strains were classified into two groups, the Coleomycetes group and the Hyphomycetes group. Compound FK463, a derivative of WF11899A, is currently in Phase 3 clinical development as a novel antifungal antibiotic.
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BACKGROUND AND OBJECTIVES: Anti-Nak(a), a platelet-specific antibody, occasionally causes platelet-transfusion refractoriness (PTR) together with human leucocyte antigen (HLA) antibodies. Anti-Nak(a) usually appears after frequent platelet transfusions or pregnancy. We report the first case of PTR caused by anti-Nak(a) alone. MATERIALS AND METHODS: A 19-year-old male patient with testicular tumour showed PTR when receiving his first transfusion of platelets. Screening for platelet antigens and platelet antibodies revealed that he had type I CD36 (Nak(a)) deficiency and that anti-Nak(a), but not anti-HLA, was present before he received his first transfusion. RESULTS: The transfusion of Nak(a)-negative, but HLA non-selected, platelets was effective in raising the platelet count. CONCLUSION: Clinically significant Nak(a) antibody was present as naturally occurring antibody in a platelet glycoprotein IV (CD36)-negative non-transfused male patient.
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Gamma/delta T cell lymphoma is very rare, and usually occurs as an extranodal tumor. We describe the case of a 16-year-old Japanese man with an unusual nodal gamma/delta T cell lymphoma with generalized lymphadenopathy and bone marrow involvement. No tumor involvement was observed in the liver, spleen, or nasal cavity. Examination for surface antigens on lymphoma cells revealed a unique phenotype, positive for CD3 and T cell receptor (TCR) gamma/delta, but negative for CD2. Genotypic analysis revealed the tumor to be of monoclonal origin and characterized by TCR gamma-chain gene rearrangement, but there was no rearrangement of the TCR beta-chain gene. Our patient's tumor responded to combination chemotherapy and subsequent allogeneic bone marrow transplantation from an HLA-matched unrelated donor. He has remained well and free of disease for 35 months.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.