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Biomedical subjects

Y Yawata

Publications and source records attributed to Y Yawata.

At least 91 records · Page 5Linked to original sources
PubMed1991

Case report: hypothyroidism as a possible cause of an acquired reversible hemolytic anemia.

The lipid composition of the red cell membrane and plasma was investigated in a patient with hypothyroidism, in whom an acquired hemolytic anemia was reversed after thyroid hormone replacement therapy. Before therapy, most of the plasma lipids were elevated. In the red cell membrane, phosphatidylcholine (PC) and free cholesterol (FC) were increased, and the free cholesterol to phospholipid (FC/PL) ratio was elevated. Erythrocyte sodium transport was also increased, while intracellular sodium and potassium concentrations were normal. After therapy, the derangement of lipid levels and sodium transport activity were normalized with improvement of the hemolytic anemia. The shape of peripheral red cells also returned to normal after treatment. These findings suggest that the derangement of the red cell membrane lipids and plasma lipids derived from hypothyroidism can be a major cause of hemolysis in this patient.

Adult↗
PubMed1991

Analysis of methylation in the c-MYC gene in five human myeloma cell lines.

Genomic alterations of the human c-MYC gene were analysed in five human myeloma cell lines established in Kawasaki Medical School and compared with those of normal lymphocytes, Raji cells from Burkitt's lymphoma, and an Epstein-Barr virus positive lymphoblastoid cell line (LCL). Although no structural chromosome aberrations at 8q24, the c-MYC locus, were distinct, the mRNA level of c-MYC in these myeloma cell lines was 30-50-fold that in normal peripheral blood lymphocytes. Regarding the methylation of c-MYC, DNAs of the myeloma cell lines were digested with MspI plus EcoRI or HpaII plus EcoRI, and hybridized with three genomic 32P-labelled probes; the first, second and third exons of the human c-MYC gene, respectively. The extent of methylation in cytosine at a single CCGG site in the third exon substantially decreased in these myeloma cell lines as compared with that in normal tonsillar B, LCL and Raji cells. No significant differences in hypomethylation between these myeloma, normal B, LCL and Raji cells was detected in the first and second exon of c-MYC. These results suggest that the hypomethylation in the third exon of c-MYC might be related to the enhanced expression of c-MYC in these human myeloma cell lines.

Aged↗
PubMed1991

[Cytoskeleton anomalies in disorders of red cell membrane proteins].

Cytoskeletal abnormalities in red cells were studied in 250 patients at our laboratory, especially on hereditary elliptocytosis (HE), hereditary spherocytosis (HS), and band 4.2 anomalies. First of all, on HE, we have found two patients of a dominantly-inherited trait of a new beta-spectrin variant with 216 kDa peptide. The contents of abnormal beta'-spectrin to the total spectrins were 7.6% in propositus, and 10.5% in her mother. As a functional abnormality, abnormal alpha beta'-spectrin dimer could not be converted to tetramer in both patients. Thus, our patients may differ from HE Nice. Secondarily, the causal relationship between red cell ankyrin and spectrin was studied on a typical HS case with abnormal chromosome, del (8p11.2-8p21.1). In this case, the deleted genetic locus was involved with loci of genes for SPH1 and ankyrin. The contents of ankyrin and other red cell membrane proteins, however, appeared to be normal on SDS-PAGE. In addition, as a unique disorder in Japan, unrelated five cases of membrane protein 4.2 deficiency were found at our laboratory. In these cases, the characteristic features were; 1) clinically uncompensated hemolysis, 2) ovalostomatocytosis, 3) markedly decreased deformability of the intact red cells by ektacytometry, if heat-treated, 4) two peptides of membrane protein 4.2 were detected in a trace amount by Western blot. Five phenotypes were categorized by Western blot, as based on the type of membrane protein 4.2 present; 1) 72 kDa peptide alone, 2) 72 kDa + 74 kDa in a trace amount, 3) 72 kDa + 74 kDa both in a trace amount, 4) 72 kDa + 68 kDa in a trace amount, and 5) complete deficiency.

Ankyrins↗
PubMed1991

[Hypoplastic leukemia successfully treated with low-dose aclarubicin: a case report].

Low-dose aclarubicin (LDACR) therapy is one of the differentiation induction therapy, such as low-dose cytosine arabinoside therapy, 1 alpha, 25 dihydroxy-vitamin D3 or retinoic acid therapy, for myelodysplastic syndrome and atypical leukemias. A 36-year-old female with hypoplastic acute myelogenous leukemia was treated with this atypical leukemias. A 36-year-old female with hypoplastic acute myelogenous leukemia was treated with this LDACR therapy. On admission, she was suffered from general fatigue and her peripheral blood smear showed pancytopenia with 23% of myeloblasts. Bone marrow examination revealed a moderately hypoplastic marrow with 35.4% of myeloblasts. She was diagnosed as having hypoplastic acute myelogenous leukemia. Thereafter, 20 mg of aclarubicin was given daily by one-shot intravenous injection for 10 days. After this LDACR therapy, myeloblasts disappeared from her peripheral blood and pancytopenia improved. Bone marrow examination showed increase in nuclear cell counts and she achieved complete remission. In this article, we report the clinical course of this patient and discuss the effect of LDACR therapy as useful chemotherapy for this patient.

Aclarubicin↗
PubMed1991

[Introductory remarks for symposium on "biological membranes of blood cells"].

Recent progress on studies of structure and functions of biological membranes has been successfully achieved. Various topics on membrane abnormalities in blood cells were selected for this symposium. First of all, in red cell disorders, abnormal red cell morphology is crucial for identification of various kinds of hemolytic anemias. In addition, cytoskeletal protein abnormalities in red cell membrane were reviewed, especially on the pathogenesis of hereditary elliptocytosis and hereditary spherocytosis. Abnormal red cell membrane fluidity was also discussed in relation to insulin receptor on red cell membranes in diabetic patients. A role of growth factors, especially G-CSF and GM-CSF, on granulocytes was described from the standpoint of membrane receptors. Platelets demonstrate various glycoproteins (GP) on their cell membrane surfaces. Abnormalities on these glycoproteins, such as GP IIb-IIIa and GP Ib-IX complex, were observed in thromboasthenia and Bernard-Soullier syndrome. In addition, arachidonic acid cascade is important in platelet functions, especially for signal transduction of extracellular messages through plasma membranes. Finally, a new application of a liposome immune lysis assay was introduced for laboratory determinations of complements, antibodies, and various marker proteins. The symposium will be extremely helpful for further understanding of the structure-function relationship and of the various disorders of blood cell membranes.

Blood Cells↗
PubMed1990

Acetylcholinesterase and lymphocyte function-associated antigen 3 found on decay-accelerating factor-negative erythrocytes from some patients with paroxysmal nocturnal hemoglobinuria are lost during erythrocyte aging.

Erythrocytes from patients with paroxysmal nocturnal hemoglobinuria are deficient in decay-accelerating factor (DAF), a factor called C8-binding protein or homologous restriction factor, acetylcholinesterase (AchE), and lymphocyte function-associated antigen 3 (LFA-3). These proteins share a common feature that glycan-inositolphospholipid anchors the protein to the membrane, suggesting that an abnormality related to this glycolipid causes multiple protein deficiencies. The relationship between the DAF, AchE, and LFA-3 defects was studied by fluorescent flow cytometric analysis. In five patients, DAF-negative erythrocytes were also AchE-negative. In three patients, a fraction of DAF-negative erythrocytes expressed subnormal levels of AchE, indicating that AchE was synthesized in these DAF-negative cells. Erythrocytes from the patients having DAF-negative, AchE-positive cells were separated according to density and analyzed for expression of DAF and AchE. Both proteins decreased with increase of cell density, suggesting that DAF-negative, AchE-positive cells become AchE-negative during erythrocyte maturation by losing AchE. A low level of LFA-3 was found on DAF-negative erythrocytes from one patient and decreased with erythrocyte maturation. These results support an idea that complete deficiency of glycan-inositolphospholipid-anchored proteins on erythrocytes could result from abnormally early termination of surface recruitment of these proteins, and subsequent dilution through cell divisions and loss from the surface.

Acetylcholinesterase↗
PubMed1990

Expression of major blood group antigens on human erythroid cells in a two phase liquid culture system.

In order to examine the sequential expression of major blood group antigens on human erythroblasts, a selective two phase liquid culture system for erythroid progenitors was established. After mononuclear cells obtained from peripheral blood were cultured in the presence of phytohemagglutinin stimulated-leukocyte conditioned medium (PHA-LCM) for 7 days (the first phase), nonphagocytic cells were recultured under hypoxic culture conditions containing 30% fetal calf serum, 1% bovine serum albumin, 300 micrograms/mL transferrin and 2 U/mL recombinant erythropoietin (the second phase). Mature (orthochromatic) erythroblasts were observed on day 4 of the second phase, and reached 57.1 +/- 3.1% of total cells on day 8, followed by the appearance of denucleated red cells, equivalent to mature red cells in peripheral blood. Hemoglobin contents reached the level of 16.8 +/- 0.7 micrograms/10(6) cells on day 8. Flow cytometric analyses revealed that, on day 3 of the second phase, cells became blood type M-positive, corresponding to the maturation of erythroid cells. Regarding the expression of ABH blood group antigens, a small number of blood type H-positive cells were initially detected on day 0 of the second phase, while blood type A-positive cells, which essentially were not observed on day 0, increased gradually corresponding to the extent of erythroid maturation. In the present system, Lewis and P1 blood group antigens were expressed at day 5 of the second phase, although autologous plasma was required to determine the expression of Lewis blood group antigens. This culture system is beneficial for studies on normal and abnormal human red cell membranes, because the erythroid progenitors in human peripheral blood were used, and a reasonable number of erythroid cells (0.5 to 1.5 x 10(7] was obtained with good maturation.

ABO Blood-Group System↗
PubMed1990

No beneficial effect of splenectomy in hereditary high red cell membrane phosphatidylcholine hemolytic anemia: clinical and membrane studies of 20 patients.

The clinical features and red cell membrane characteristics of 20 patients with hereditary high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA) were studied in relation to the effect of splenectomy. After splenectomy, anemia worsened and the extent of increased hemolysis in these patients was unchanged, indicating a contraindication for splenectomy. Concomitant with these results in clinical hematology, marked stomatocytic changes, increased red cell phosphatidylcholine content, and enhanced sodium transport, which were observed before splenectomy, were not improved by splenectomy.

Adolescent↗
PubMed1990

[Ectopic production of amylase by a non-producing type of multiple myeloma].

The patient was a 64-year-old woman who was admitted to our hospital because of lumbago. A diagnosis of multiple myeloma (non-producing type) was made, based on (1) the presence of multiple osteolytic lesions, (2) hypercellular marrow with 64.2% plasmacytoid malignant cells, (3) no monoclonal gamma-globulin was detected in the serum and urine, and (4) abnormal monoclonal gamma-globulin was also not detected in the cytoplasm and membranes of these malignant cells. After several courses of chemotherapy, a pleural effusion infiltrated by myeloma cells developed and the patient's serum contained a markedly increased amylase activity of salivary-type. Amylase activity was also detected in vitro in the supernatant of cultured myeloma cells established from the patient's pleural effusion. The presence of alpha-amylase in the myeloma cells, which were derived from pleural effusion, was demonstrated immuno-histochemically. These observations indicates that amylase was ectopically produced by these myeloma cells. Interestingly, 14 out of 20 metaphases in the cells derived from pleural effusion showed translocation of 1p22 near the region of 1p21, where the amylase gene was assigned.

Amylases↗
PubMed1990

Clinical usefulness of vinca alkaloid slow infusion in the treatment of chronic refractory idiopathic thrombocytopenic purpura: a multicenter cooperative study.

Thirty-eight patients with chronic refractory idiopathic thrombocytopenic purpura (ITP) were treated with weekly slow infusions of vincristine (0.02 to 0.04 mg/kg) or vinblastine (0.1 to 0.2 mg/kg). Twenty-two patients showed good to excellent responses after one to eight infusions. These responses were generally short, and lasted only in six patients after discontinuance of the therapy. The efficacy was comparable between vincristine and vinblastine. Neither the age, sex, duration of the disease, prior splenectomy nor combined use of adrenocortical steroids was likely to have influenced the therapeutic effect. Side effects such as peripheral neuropathy, alopecia, gastrointestinal symptoms and leukopenia occurred in 34 patients, and necessitated discontinuance of the therapy in eight patients. Slow infusions of vinca alkaloids can be an effective means of inducing platelet response in patients with chronic refractory ITP, but frequent side effects limit its clinical usefulness.

Adolescent↗
PubMed1990

Evolution and development of membrane components in erythroid precursor cells in newly-developed two phase culture system.

A selective two phase liquid culture system for human erythroid progenitors was established, utilizing mononuclear cells obtained from human peripheral blood. The culture was performed in the presence of PHA-leukocyte conditioned medium for 7 days as the first phase, and nonphagocytic cells were recultured under hypoxic culture conditions containing iron-saturated transferrin and erythropoietin. During the second phase of the culture, differentiation to orthochromatic erythroblasts was observed on day 4, and to denucleated cells on day 8 with 16.8 +/- 0.7 micrograms/10(6) cells of hemoglobin level, respectively. Flow cytometric analyses revealed that, on day 3, cells became type M-positive, and the expression of ABH increased gradually corresponding to the extent of erythroid maturation. Lewis antigens and P antigens were expressed at day 5. The system is beneficial for studies on human membrane disorders, because the erythroid progenitors in human peripheral blood were utilized and the reasonable number of erythroid cells (0.5-1.5 x 10(7] was obtained with good erythroid maturation, such as denucleated erythrocytes.

Antigens↗
PubMed1989

Establishment of five human myeloma cell lines.

Five human myeloma cell lines, KMM-1, KMS-5, KMS-11, KMS-12-PE, and KMS-12-BM, have been established at Kawasaki Medical School since 1980. As the KMS-12-PE and KMS-12-BM lines were obtained from the same patient, these five cell lines have been derived from four patients with multiple myeloma. The five myeloma cell lines are stably growing at present in RPMI 1640 medium supplemented with 10% fetal bovine serum. They can also grow in a defined culture medium without serum. That these cell lines were human myeloma cells was confirmed by the following findings. Ultrastructurally, all five cell lines showed features characteristic of plasma cells. KMM-1 and KMS-11 cells secreted lambda and kappa chains into the culture medium, respectively, but the other cell lines produced no immunoglobulins. KMM-1 expressed cytoplasmic lambda antigen, KMS-5 showed cytoplasmic delta, and KMS-11 expressed surface kappa, whereas KMS-12-PE and KMS-12-BM cells showed no surface or cytoplasmic immunoglobulins. Regarding reaction with a monoclonal plasma cell antibody (PCA-1), four of the five lines were positive, the exception being KMS-5. Another monoclonal antibody (CD38), which also recognizes plasma cells, responded to KMM-1, KMS-12-PE, and KSM-12-BM. KMS-5 cells expressed acute lymphoblastic leukemia antigens (CALLA). These data suggest that such lines as KMM-1, KMS-11, KMS-12-PE, and KMS-12-BM represent later stages of B-cell differentiation, and that KMS-5 represents a relatively early stage of B-cell differentiation. All the cell lines lacked Epstein-Barr virus nuclear antigen, showed abnormal karyotypes of human origin, and differed from each other in the isozyme patterns examined. Only KMS-5 was tumorigenic when transplanted subcutaneously into nude mice.

Aged↗
PubMed1989

Two human myeloma cell lines, amylase-producing KMS-12-PE and amylase-non-producing KMS-12-BM, were established from a patient, having the same chromosome marker, t(11;14)(q13;q32).

Two human myeloma cell lines, KMS-12-PE and KMS-12-BM, were established from a 64-year-old woman with a non-producing type of multiple myeloma. The KMS-12-PE line originated from the pleural effusion and the KMS-12-BM from the bone marrow. These two lines showed the same chromosome marker, t(11:14)(q13:q32). However, their phenotypes of surface markers differed from each other. KMS-12-BM cells were positive to CD20, CD38 and PCA-1. showing the plasmacytoid (immature plasma cell) stage of B-cell differentiation, while KMS-12-PE cells were positive to CD38 and PCA-1, but not to CD20, indicating the terminal differentiated stage of B-cells. As seen in the pleural effusion of the patient. KMS-12-PE cells ectopically produced a salivary type of amylase, but KMS-12-BM cells did not. Interestingly, the chromosome abnormality of del(1)(p22----pter) near the region of 1p21, where the amylase gene was assigned, was noticed in as many as 76% of KMS-12-PE cells.

Amylases↗