Search PubMed⌕ Search

Biomedical subjects

Y Kurata

Publications and source records attributed to Y Kurata.

At least 145 records · Page 8Linked to original sources
PubMed1991

Flow cytometric analysis of anti-platelet antibodies in patients with chronic idiopathic thrombocytopenic purpura (ITP) using acid-treated, formalin-fixed platelets.

Acid treatment of normal washed platelets prepared by albumin density gradient centrifugation followed by formalin fixation effectively eliminates HLA class I antigens from the platelet surface, without altering the immunoreactivity of platelet membrane glycoproteins Ib and IIb/IIIa complex. Using these platelets, flow cytometric analysis was performed on a total of 20 sera from different patients with chronic ITP, and revealed an inverse linear correlation between the platelet count and the mean fluorescence intensity which represents a relative amount of platelet-bound IgG. These results suggest that acid-treated, formalin-fixed platelets can be used as specimens to detect anti-platelet antibodies to differentiate from those to HLA-class I antigens.

Acids↗
PubMed1991

Effects of aprindine on conduction velocity and Vmax in guinea-pig papillary muscles.

One of the effects of antiarrhythmic drugs is the reduction of conduction velocity. Cable theory predicts that there is a nonlinear relationship between conduction velocity and upstroke velocity (Vmax) of action potential. By using conventional microelectrode techniques, aprindine-induced reduction of Vmax of action potential and conduction velocity in guinea-pig papillary muscles were measured. Aprindine-produced, use-dependent, and concentration-dependent changes in conduction velocity and the decline of square of conduction velocity was well fit by a single exponential. Time constants for square of conduction velocity were comparable to simultaneously measured time constants for effects of Vmax. At a concentration of 1 to 10 microM aprindine, onset changes between Vmax and conduction velocity had a log-linear relationship in a predicted fashion. Whereas, in the recovery process from aprindine-induced depression, slow recovery time course of conduction velocity was observed. In conclusion, in the presence of aprindine, only onset block of conduction velocity can be analyzed quantitatively in the relationship to observation on Vmax in vitro. These results suggested that in the presence of aprindine, the recovery of internal conductance may be slower than that of Vmax.

Action Potentials↗
PubMed1991

13-Week oral toxicity study of captafol in F344/DuCrj rats.

Captafol fed at concentrations of 0, 0.075, 0.15, 0.3, and 0.6% to both sexes of F344 rats for 13 weeks produced dose-related decreases in body weight in males and females given 0.15% or higher concentrations. A dose-dependent decrease in urinary pH was observed in males receiving 0.3 or 0.6% and in females given 0.15% or higher concentrations of captafol. The 0.3 and 0.6% doses produced slight increases in leukocyte count and glutamic-pyruvic transaminase activity in females, along with a mild increase in alkaline phosphatase activity in the 0.6% case. The liver- and kidney-to-body weight ratios were increased in both male and female rats. Histopathological changes were observed in the forestomach, liver, and kidney. Squamous cell hyperplasia and edema accompanied by polynuclear leukocyte infiltration and dilation of vessels in the lamina propria were observed in the forestomach of both sexes given 0.15% or higher concentrations. Oval cell proliferation was apparent around Glisson's sheath in the livers of females given 0.3 and 0.6% captafol. Multifocal appearance of karyocytomegaly and tubular cell atypia in the proximal tubules of the kidney was found in the 0.3 and 0.6% groups of both sexes.

Alanine Transaminase↗
PubMed1991

DNA synthesis and scanning electron microscopic lesions in renal pelvic epithelium of rats treated with bladder cancer promoters.

The proliferation response of rat renal pelvic epithelium, lined by transitional epithelium, to administration of various bladder cancer promoters was investigated. In addition, prostaglandin E2 (PGE2), lipid peroxide (LPO), malondialdehyde (MDA) and cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels were assessed in urine of rats given the non-promoter L-ascorbic acid (AsA) and the promoters sodium L-ascorbate (AsA-Na) or sodium bicarbonate (NaHCO3) for 4 or 8 weeks. DNA synthesis in the renal pelvic epithelium, as assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation, was increased in the groups given AsA-Na, an extremely high dose of sodium chloride (NaCl), tert-butylhydroquinone (TBHQ) or ethoxyquin (EQ). Moreover, with the exception of AsA-Na, all treatments that induced an elevation of DNA synthesis also caused morphological epithelial alterations as observed by scanning electron microscopy (SEM). Treatment with butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) did not result in any proliferative response of the rat renal pelvis. No treatment-related changes in urinary PGE2 and cyclic AMP were noted, although AsA-Na and AsA but not NaHCO3 reduced levels of LPO and MDA in the urine. The results indicate that while the response of renal pelvic epithelium to certain bladder cancer promoters is similar to that of the bladder itself, none of the urinary cellular growth or free radical biochemical parameters is directly related to urothelial cell proliferation.

Animals↗
PubMed1991

No promotion of urinary bladder carcinogenesis by sodium L-ascorbate in male ODS/Shi-od/od rats lacking L-ascorbic acid-synthesizing ability.

The promoting effects of sodium L-ascorbate (Na-AsA) on two-stage urinary bladder carcinogenesis were investigated in male ODS/Shi-od/od rats. This strain genetically lacks L-ascorbic acid-synthesizing ability, which is controlled by a single autosomal recessive od gene; heterozygous ODS/Shi(-)+/od, normal ODS/Shi(-)+/+ or F344 rats are able to synthesize L-ascorbic acid. In experiment 1, ODS/Shi-od/od and F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 2 weeks and then basal CA-1 diet with or without 5% Na-AsA for 32 weeks. F344 rats were sensitive to the promoting effects of Na-AsA, whereas ODS/Shi-od/od rats were resistant. Administration of Na-AsA increased the urinary pH and the urinary concentrations of Na+ and total ascorbic acid in all strains. In experiment 2, DNA synthesis in the urinary bladder epithelium of F344 rats fed MF diet or CA-1 diet was increased by exposure to 5% Na-AsA for 8 weeks, but not in ODS/Shi-od/od rats fed CA-1 diet. In experiment 3, ODS/Shi-od/od, ODS/Shi(-)+/od and ODS/Shi(-)+/+ rats were given 0.05% BBN for 4 weeks and then CA-1 diet with or without 5% Na-AsA for 32 weeks. ODS/Shi-od/od, ODS/Shi(-)+/od and ODS/Shi(-)+/+ rats were resistant to the promoting effects of Na-AsA in two-stage urinary bladder carcinogenesis. The urinary pH and the urinary concentrations of Na+ and total ascorbic acid in ODS/Shi-od/od, ODS/Shi(-)+/od and ODS/Shi(-)+/+ rats were increased by the administration of Na-AsA. These results indicate that ODS/Shi-od/od rats are resistant to the promoting effects of Na-AsA in two-stage urinary bladder carcinogenesis, and that the susceptibilities of ODS/Shi-od/od rats are regulated by genes different from the gene at the od locus.

Animals↗
PubMed1991

Dose-dependent effects of 2-acetylaminofluorene on hepatic foci development and cell proliferation in rats.

Dose-dependent development of pre-neoplastic liver cell foci induced by 2-acetylaminofluorene (2-AAF) was investigated in relation to cell-proliferative activity. Male F344 rats were initially given a single i.p. injection of diethylnitrosamine (DEN, 200 mg/kg) and starting 2 weeks later received diets containing 2-AAF at dose levels of 150, 100, 60, 45, 35 or 30 p.p.m., 500 p.p.m. phenobarbital (PB) or basal diet as a control for 6 weeks. Two-thirds partial hepatectomy (PH) was performed at week 3. The rats were sequentially killed from weeks 0 to 16 and liver sections were analysed by double staining for both BrdU incorporation and glutathione S-transferase placental form (GST-P) expression. 2-AAF increased numbers and areas of GST-P positive (GST-P+) foci in a dose-dependent manner, especially after PH. Proliferation of hepatocytes, as indicated by BrdU labelling indices (LI), was higher in GST-P+ foci than in surrounding hepatocytes in all 2-AAF-treated groups, even after cessation of carcinogen administration. Proliferative response of hepatocytes to PH was delayed in rats treated with the highest dose of 2-AAF in both foci and in surrounding areas possibly due to the 2-AAF toxicity. In the PB treated group, the results were similar to those for the lower dose 2-AAF-treated groups. It is concluded that the development of GST-P+ foci and cell proliferation in GST-P+ foci are directly related to 2-AAF treatment in a dose-dependent manner and the present assay system is reliable for detection of carcinogenicity of chemicals even at low doses.

2-Acetylaminofluorene↗
PubMed1991

Slow recovery of conduction velocity from use dependent inhibition induced by quinidine in guinea pig ventricular myocardium.

STUDY OBJECTIVE: The aim was to investigate whether the use dependent effects of antiarrhythmic drugs on the Na+ current could be applied to explain their effects on impulse conduction. DESIGN: Trains of rapid stimuli were applied to guinea pig papillary muscles via an electrode in the presence of quinidine (20 and 60 mumol.litre-1), and the conduction velocity was determined from the time difference between two signals of the maximal rate of rise (dV/dtmax) of the action potentials at two separate sites. The relationship of the time constants of the onset and recovery from the use dependent inhibition induced by quinidine was determined for the dV/dtmax and the conduction velocity. EXPERIMENTAL MATERIAL: Six male Hartley guinea pigs weighing 200 to 300 g were killed by a blow to the head and the papillary muscles were rapidly excised from the right ventricles. The preparations were superfused with Tyrode solution. MEASUREMENTS AND MAIN RESULTS: The rate of onset of the use dependent inhibition of conduction velocity and that of the square of conduction velocity were both faster than the simultaneously measured rate of onset of dV/dtmax inhibition induced by 20 mumol.litre-1 quinidine at high frequency stimulation. The relation between the rates of onset of the use dependent inhibition of conduction velocity (and the square of conduction velocity) and dV/dtmax became weak with low frequency stimulation and in the presence of 60 mumol.litre-1 quinidine. However, the recovery of conduction velocity (and the square of conduction velocity) from quinidine induced use dependent blockade, as measured by the extrastimulation method, appeared to be slower than the recovery of dV/dtmax. These results may be explained by a transient change in intracellular and intercellular conditions, such as an increase in internal resistance. CONCLUSIONS: The onset and recovery of the use dependent inhibition of conduction by antiarrhythmic drug may not always parallel the changes of the dV/dtmax of action potential in multicellular muscle preparations.

Action Potentials↗
PubMed1991

B cells expressing CD5 antigen are markedly increased in peripheral blood and spleen lymphocytes from patients with immune thrombocytopenic purpura.

By two-colour flow cytometric analysis, we examined the proportion of B lymphocytes bearing CD5 cell surface antigen (CD 5+ B cells), which are capable of producing autoantibodies, both in peripheral blood and spleen from patients with chronic immune thrombocytopenic purpura (ITP). The percentage of CD5+ B cells in peripheral blood lymphocytes (PBLs) was significantly increased (P less than 0.005) in patients with ITP (3.7 +/- 2.2%, n = 30) as compared with normal controls (1.7 +/- 0.7%, n = 28). However, there was no correlation between the percentages of circulating CD5+ B cells and platelet counts. The percentage of splenic CD5+ B cells in ITP patients was much more increased (9.0 +/- 4.5%, n = 9), P less than 0.005) compared with that of other disorders (3.2 +/- 0.5%, n = 5). Furthermore, isolated splenic CD5+ B cells from two out of five ITP patients produced high levels of IgM-type, platelet-bindable antibodies (PBIgM) after stimulation with Staphylococcus aureus Cowan I (SAC), while CD5- B cells isolated from the same spleen or splenic CD5+ B cells from other non-autoimmune disorders failed to produce significant amount of PBIgM. In three ITP patients, no increase in PBIgM was detected despite SAC stimulation. The increased proportion of CD5+ B cells in peripheral blood and spleen, and their ability to produce anti-platelet antibodies indicate that they are directly involved in the autoimmune pathogenesis in ITP.

Adult↗
PubMed1991

The effect of TYB-3823, a new antiarrhythmic drug, on sodium current in isolated cardiac cells.

1. Sodium current (INa) blockade by TYB-3823, a newly synthesized antiarrhythmic agent, was investigated in isolated single ventricular myocytes by use of the whole cell patch-clamp technique. 2. TYB-3823 blocked INa under steady-state conditions (Kd,rest = 500 microM, Kd,i = 4.9 microM), findings consistent with a shift in the steady state INa availability curve to more negative potentials. 3. TYB-3823 produced use-dependent block at 2 Hz in conjunction with increase in pulse duration (5-300 ms), that was markedly enhanced at less negative holding potentials. 4. The time course of the onset of block was accelerated and the degree of use-dependent block was decreased at more negative holding potential. The time course of the onset of block was accentuated with enhancing block at more positive holding potentials. 5. The time course of recovery from use-dependent block was accelerated at more negative holding potentials but was accentuated at more positive holding potentials. 6. These results suggest that both tonic block and use-dependent block of sodium channels in cardiac tissue might result from an interaction of TYB-3832 with sodium channels mainly in the inactivated channel states and the kinetics of the interaction between drug and receptor may be modulated by the inactivation gate.

Animals↗
PubMed1991

Antiplatelet glycoprotein Ib monoclonal antibody (OP-F1) totally abolishes ristocetin-induced von Willebrand factor binding, but has minimal effect on the botrocetin-induced binding.

We describe here a new antiplatelet glycoprotein (GP) Ib monoclonal antibody (MoAb) designated OP-F1 (IgG1 kappa). Both OP-F1 and a well-characterized anti-GPIb MoAb, AP-1, totally abolished ristocetin-induced von Willebrand factor (vWF) binding to platelets and desialylated vWF binding to platelets at an IgG concentration of 2-8 micrograms/ml. AP-1 also blocked snake venom botrocetin-induced vWF binding at a similar IgG concentration, whereas OP-F1 had a minimal effect on botrocetin-induced binding. At a higher IgG concentration (150 micrograms/ml), OP-F1 inhibited botrocetin-induced binding by 50%. AP-1 (IgG) did not interfere with binding of [125I]OP-F1 (IgG) to platelets. Thus, the epitope involved in the binding of OP-F1 or AP-1 appears to be quite different. These results suggest that the vWF binding site(s) on the GPIb molecule generated by these inducers is in close proximity but not completely identical.

Antibodies, Monoclonal↗
PubMed1991

[Prenatal evaluation of the platelet counts in the fetuses and the neonates of the mothers complicated with idiopathic thrombocytopenic purpura].

We investigated 25 pregnancies with ITP. The results were as follows. 1. The platelet counts of the maternal blood just before delivery were not correlated with those of the cord blood. 2. It was suggested that the maternal PAIgG value just before delivery could foretell the onset of neonatal thrombocytopenic purpura. 3. The platelet counts in fetal scalp blood were correlated with those of the cord blood, but falsely lower platelet counts were found in the fetal scalp samples. 4. We saw 5 cases of percutaneous umbilical blood sampling (PUBS) in pregnancies with ITP. PUBS was found to be a useful and safe method. The indications for PUBS and fetal platelet transfusion in pregnancy with ITP are discussed.

Cesarean Section↗
PubMed1991

[Burkitt's type ALL with numb chin syndrome as an initial manifestation].

A case of Burkitt's type ALL with numb chin syndrome as the initial manifestation is described. A 57-year-old Japanese male was admitted to our hospital in November 14, 1989 because of paresthesia at the chin and lower lip with diplopia and ptosis. Neurological examination revealed oculomotor paralysis of the right side and hypesthesia on the chin, lower lip and buccal mucous membrane. Laboratory findings showed increased leukocyte count. Bone marrow aspirate revealed hypercellular marrow with 92.3% leukemic cells which had vacuoles in the cytoplasm and surface marker of IgM, kappa type. The abnormalities of karyotype included t(8;14). He was treated with chemotherapy and radiation. His conditions were temporarily improved, but relapsed later and died in March 6, 1990. Leukemic infiltrations to the trigeminal nerve were found in autopsy. The relationship between lymphoid malignancies and numb chin syndrome was discussed.

Burkitt Lymphoma↗
PubMed1990

Analyses of thrombocytopenia in idiopathic thrombocytopenic purpura-prone mice by platelet transfer experiments between (NZW x BXSB)F1 and normal mice.

Male (NZW x BXSB) F1 (W/B F1) mice, which develop lupus nephritis, myocardial infarction, and thrombocytopenia, showed reduced platelet lifespan (PLS) and increased platelet-associated antibody (PAA) values. There were statistically significant correlations between the increase in PAA values and either the reduction in PLS or the decrease in platelet counts. This and the results of platelet transfer experiments between old male W/B F1 mice and either female W/B F1 or normal BALB/c mice indicate that PAAs on the platelet surface play a crucial role in the destruction of platelets in W/B F1 mice. The mechanism of thrombocytopenia observed here appears similar to that of human idiopathic thrombocytopenic purpura (ITP). Therefore, we think that W/B F1 mice are a potentially useful animal model for investigating the effectiveness and mode of action of therapeutic agents in human ITP, and that they may provide additional information on the basic mechanisms of this autoimmune phenomenon.

Animals↗
PubMed1990

Glucocorticoid effects on myeloma cells in culture: correlation of growth inhibition with induction of glucocorticoid receptor messenger RNA.

Glucocorticoids are widely used for the treatment of multiple myeloma. To investigate the direct actions of glucocorticoids on myeloma cells, we have used three cell lines of human multiple myeloma, OPM-1, OPM-2, and RPMI 8226. When growth curves of these cells were examined, OPM-1 cells were resistant, while OPM-2 were sensitive to dexamethasone (DEX). In cultures of OPM-2 cells, addition of DEX led to virtual cessation of growth, with only 16% of the residual cells viable after 4 days. RPMI 8226 appeared to be slightly sensitive, showing some slowing of growth for several days in DEX, with later recovery. Viabilities of OPM-1 and RPMI 8226 cells were not affected. Secretion of immunoglobulin (Ig-lambda) was also partially suppressed, by 30% in OPM-2 and 14% in OPM-1. No significant suppression was observed in RPMI 8226. To explore the mechanism of these differential responses to the steroid, glucocorticoid receptor (GR) was examined. Binding assays showed high affinity binding sites in all three cell lines: 64 +/- 11 fmol/10(6) cells in OPM-1, 78 +/- 14 in OPM-2, and 62 +/- 16 in RPMI 8226. Nuclear transfer of GR and DNA-cellulose binding after heat activation appeared similar in all three cell lines. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cytosol proteins labeled with [3H]dexamethasone mesylate showed a GR of Mr 95,000 in all three. When GR mRNA was studied in these cells, all of them had GR mRNA of approximately 7 kilobases, but OPM-2 and RPMI 8226 had 3 times more GR mRNA than OPM-1. OPM-2 GR mRNA was induced 2-fold by DEX treatment at 5 x 10(-9) M or greater. OPM-1 GR mRNA was much less sensitive, with no response at less than 10(-6) M DEX and only 1.5-fold induction at that concentration. These results demonstrate that some myeloma cells can be killed by a direct action of glucocorticoids. The quantity and affinity of GR in the cells were not predictive of this response. Therefore, we propose that the resistance of OPM-1 and the relative resistance of RPMI 8226 to glucocorticoid inhibition of cell growth is by post-receptor mechanisms. The high sensitivity of induction of GR mRNA in OPM-2 may correlate with glucocorticoid-evoked cell kill.

Blotting, Northern↗
PubMed1990

Carcinogenicity study of methyl hesperidin in B6C3F1 mice.

A long-term carcinogenicity study of methyl hesperidin, a compound of the vitamin P group, was carried out in B6C3F1 mice receiving dietary concentrations of 0, 1.25 or 5%. Administration was continued for 96 wk and then the mice were maintained on basal diet for an additional 8 wk. Growth retardation during the experiment with final changes in organ weights were observed in females given the 1.25% dose of methyl hesperidin and in both sexes receiving the 5.0% treatment. However, no biologically significant effects were evident with respect to mortality or clinical signs. Furthermore, treatment with methyl hesperidin did not result in any changes in haematology, clinical chemistry and urinalysis data. On histological examination, no significant alteration of non-neoplastic and neoplastic lesion incidence was observed in treated mice. The results thus demonstrated that methyl hesperidin lacked any carcinogenicity for B6C3F1 mice in the 96-wk feeding regimen used in this study.

Administration, Oral↗
PubMed1990

Bladder epithelial hyperplasia in F344 rats after intravesical instillation of the antitumor chemotherapeutic agents Adriamycin and mitomycin C.

The effects of intravesical instillation of the antineoplastic antibiotics, Adriamycin or mitomycin C, on the urinary bladder epithelium of female F344 rats were evaluated using a combined immunohistochemical and morphological approach. Four weeks treatment with Adriamycin or mitomycin C induced an increase of DNA synthesis and was associated with simple hyperplasia characterized by elevated nuclear cytoplasmic ratios, cytomegaly and pleomorphism. Under the scanning electron microscope (SEM), luminal cell surface alterations such as pleomorphic microvilli were observed. Severity of the lesions was greatest in the Adriamycin group and although treatment of the saline vehicle alone also brought about development of simple hyperplasia, this was very slight and not accompanied by cellular pleomorphism. The present results demonstrated that intravesical instillation of antineoplastic agents can cause a proliferative response and cytotoxicity after only short-term treatment and suggest that this chemotherapy could itself play a possible role in promotion of bladder carcinogenesis or cancer development.

Administration, Intravesical↗