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Biomedical subjects

H Hashimoto

Publications and source records attributed to H Hashimoto.

At least 901 records · Page 50Linked to original sources

HLA-DP+ T cells and deficient interleukin-2 production in patients with systemic lupus erythematosus.

In patients with systemic lupus erythematosus (SLE), frequency of the T cells positive for HLA-DP, one of the major histocompatibility complex (MHC) class II molecules, was markedly increased in peripheral blood lymphocytes (PBL), in association with an increase in the amount of specific cytoplasmic transcript of the HLA-DP gene segment. Cell cycle analysis showed that HLA-DP is an early activation marker of T cells and that the high ratios of HLA-DP+ T cells from SLE patients are associated with high frequency of T cells at early activation phases, mainly of G1A. Initial high ratios of HLA-DP+ T cells decreased to a great extent during 4 days of in vitro culture, in the absence of mitogens. This event was associated with decreases in the amount of HLA-DP transcript and the disappearance of activated T cells. Studies on the interleukin 2 (IL-2) production of T cells from patients with SLE demonstrated that while the PBL rich in HLA-DP+ T cells show a markedly low production of IL-2, preculture of these PBL restores the ability to produce IL-2. Thus, it appears that the T cells in patients with SLE are essentially intact with regard to the capacity to produce IL-2 and that T cell activation events continuously occurring in SLE patients are related to a deficiency in IL-2 production. The possible underlying mechanisms are discussed.

Adolescent↗

Identification of a prostacyclin receptor coupled to the adenylate cyclase system via a stimulatory GTP-binding protein in mouse mastocytoma P-815 cells.

A stable analogue of prostacyclin, iloprost, specifically bound to 30,000 x g pellet (the membrane fraction) prepared from mouse mastocytoma P-815 cells. The binding was dependent on time, temperature and pH, and absolutely required a divalent cation. The equilibrium dissociation constant and the maximal concentration of the binding site as determined by Scatchard plot analysis were 10.4 nM and 1.12 pmol/mg of protein, respectively. The Hill coefficient was 1.0, indicating a single entity of binding site and no cooperativity. The binding site was highly specific for iloprost among PGs tested (iloprost much greater than PGE1 greater than carbacyclin greater than PGE2). In contrast, the membrane fraction had the binding site specific for PGE2 and PGE1, which was distinct from the prostacyclin receptor. The dissociation of bound [3H]iloprost from the membrane fraction was specifically enhanced by guanine nucleotides. Furthermore, iloprost dose-dependently enhanced the activity of adenylate cyclase in a GTP-dependent manner. These results indicate that a specific prostacyclin receptor is coupled to the adenylate cyclase system via a stimulatory GTP-binding protein in mastocytoma cells.

Adenine Nucleotides↗

Biochemical basis of the prevention of 6-thiopurine toxicity by the nucleobases, hypoxanthine and adenine.

Co-incubation of human leukemia cell lines with naturally occurring nucleobases (hypoxanthine or adenine) significantly prevented the cytotoxic activity of 6-thiopurines. Extracellular hypoxanthine decreased the transport of 6-mercaptopurine into cells, but adenine had no significant effect. However, intracellular thioinosine monophosphate accumulation in the presence of 10 microM, 6-mercaptopurine was reduced to below 1% or 10% of that of the controls when 50 microM hypoxanthine or adenine was added, respectively. Finally, in adenine phosphoribosyl transferase deficient mutants, adenine provided no protective effect against 6-thiopurines, whereas hypoxanthine retained its modulating activity. These data suggest that the nucleobases compete with 6-thiopurines for the ribose-phosphate donor, 5'-phosphoribosyl-1-pyrophosphate, thus preventing the formation of active metabolites of 6-thiopurines.

2-Aminopurine↗

Cell type dependent activation of poly (ADP-ribose) synthesis following treatment with etoposide.

Treatment of human non-lymphoid cell lines, HL-60 and U937, with etoposide stimulated poly (ADP-ribose) synthesis three- to fourfold, whereas no significant effects were observed in the lymphoid cell lines, Molt4 and CEM. This was confirmed by either an increased uptake of radio-labelled NAD into the acid-insoluble fraction or a fall in cellular NAD levels, which was counteracted by 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase. On the other hand, another DNA damaging agent, N-methyl-N'-nitro-N-nitrosoguanidine augmented poly(ADP-ribose) synthesis equally in both cell types. These results taken together indicate that the activation of poly(ADP-ribose) synthesis following exposure to etoposide is a cell type specific phenomenon.

Cell Survival↗

Pregnancy zone protein inhibits production of interleukin-2 but does not affect interleukin-2 receptor expression on T cell activation.

The effect of pregnancy zone protein (PZP), which exhibits increased levels in the blood during pregnancy, on T cells was examined. PZP was found to suppress DNA synthesis following stimulation with phytohemagglutinin (PHA), concanavalin A (ConA) or CD3 antigen or in the mixed lymphocyte reaction (MLR). This effect of PZP was mediated by a reduction in interleukin-2 (IL-2) production, and was abolished by exogenous recombinant IL-2 administration. PZP did not affect the proliferation of T cells following stimulation with the calcium ionophore A23187 and phorbol 12-myristate 13-acetate (TPA). These results suggest that PZP acts on the T cell surface and reduces IL-2 production, but not IL-2R expression, and does not directly affect Ca2+ influx or protein kinase C.

Calcimycin↗

Leiomyoblastoma of the epididymis in a child.

A case of leiomyoblastoma of the epididymis in a 3-year-old boy is presented. Left high inguinal orchiectomy was performed. Light and electron microscopic examinations revealed a 3.5 X 2.3 X 1.5 cm. tumor continuous with the tail of the epididymis. The lesion proved to be a leiomyoblastoma of the epididymis. Leiomyoblastoma is a form of leiomyoma mainly composed of immature smooth muscle cells. The absence of keratin, epithelial membrane antigen and negative results by alcian blue stain indicated that there were no adenomatoid elements in the tumor.

Child, Preschool↗

Isoenzyme profiles of creatine kinase, lactate dehydrogenase, and aspartate aminotransferase in the diabetic heart: comparison with hereditary and catecholamine cardiomyopathies.

STUDY OBJECTIVE: The aim was to investigate the redistribution of isoenzymes, clinically important markers of myocardial necrosis, in the diabetic heart and compare it with that investigated in other types of cardiomyopathies. DESIGN: Myocardial isoenzyme activity of creatine kinase (CK), lactate dehydrogenase (LD) and aspartate aminotransferase (AST) was measured in animals with diabetic, hereditary, and catecholamine cardiomyopathies. SUBJECTS: Diabetic rats (4 and 8 weeks after intravenous streptozotocin, n = 21), Bio 14.6 hamsters (30, 90, 160 and 240 days old, n = 29), and rats injected with isoprenaline (0.25, 0.5 and 1.0 mg.kg-1.d-1 for 3 weeks, n = 20) were used. Controls were age matched intact animals (n = 8-11). MEASUREMENTS AND MAIN RESULTS: Total CK and CK MM activity decreased in all groups. CK MB and BB decreased by 62 and 52% in diabetic rats, but increased by 40 and 33% in Bio hamsters and by 9 and 96% in isoprenaline treated rats. Thus the CK-B subunit decreased by 61% in diabetics and increased by 33 and 38% in Bio and isoprenaline groups, while the CK-M subunit decreased in all groups. Mitochondrial CK decreased in diabetic and isoprenaline groups. Total LD activity increased in diabetics and decreased in Bio. LD-H subunit increased by 21% in diabetics and decreased by 19 and 18% in Bio and isoprenaline groups. Accordingly the proportion of LD-M subunit, an index of anaerobic metabolism, decreased in diabetics and increased in Bio and isoprenaline groups. Changes in CK-M and CK-B subunits and the LD-M proportion in diabetic heart were normalised by insulin. Total AST activity decreased in diabetics because of the reduction in mitochondrial AST. CONCLUSIONS: Increased LD-M proportion and CK-B observed in Bio and isoprenaline groups may be a metabolic "compensation" to decreased myocardial perfusion and substrate. Decreased LD-M proportion and CK-B in the diabetic heart was insulin dependent and may indicate either lack of "compensation" to myocardial ischaemia or absence of ischaemia per se. Decreased myocardial CK and CK MB activity possibly causes underestimation of enzymatically assessed infarct size in the diabetic heart.

Animals↗

Sheet of scar causes trapdoor deformity: a hypothesis.

The trapdoor deformity has been thought to be the result of contraction of the semicircular scar of the skin surface. The hypothesis is presented that a sheet of internal scar is primarily responsible for raising the skin inside the semicircle.

Biomechanical Phenomena↗

Comparative effects of antidepressants, amitriptyline, and maprotiline on intraventricular conduction, effective refractory period, and incidence of ventricular arrhythmias induced by programmed stimulation in dog hearts after myocardial infarction.

The effects of amitriptyline and maprotiline, standard tricyclic and tetracyclic antidepressants, on intraventricular conduction, the effective refractory period (ERP), and the incidence of ventricular arrhythmias induced by programmed stimulation were studied and compared in dog hearts after myocardial infarction. Amitriptyline at doses of 1-3 mg/kg significantly slowed ventricular conduction of the infarcted zones in a frequency-dependent and dose-dependent manner. Amitriptyline at doses of 2 and 3 mg/kg slowed conduction slightly in normal zones. The ERP was prolonged by amitriptyline at a dose of 2 mg/kg. Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed stimulation. Maprotiline at doses of 1-3 mg/kg slowed conduction in infarcted zones to a lesser extent as compared with amitriptyline, although severely depressed conduction in the infarcted zone was obviously slowed by maprotiline. Maprotiline did not increase the incidence of ventricular arrhythmias significantly. From the present results, maprotiline appears to have less cardiac toxicity than amitriptyline, although maprotiline produces a slight decrease in conduction of infarcted zones.

Action Potentials↗

A human case of zoonotic onchocerciasis in Japan.

A 2-year-old girl living in southwestern Japan had a nodule of 2 months' duration on the left foot. A biopsy from the lesion showed transverse sections of a worm surrounded by granulomatous tissue. The worm was identified as an Onchocerca sp. from the morphological characteristics such as relatively thick cuticles, annular ridges on the cortical layer, and high somatic muscles. Positive serological tests using ELISA for Onchocerca gutturosa and Onchocerca volvulus supported the diagnosis. This was the first case of zoonotic Onchocerca infection detected in Japan. The clinicopathological aspects of zoonotic onchocerciasis of this case were discussed.

Child, Preschool↗

Distribution and characterization of hemolytic, and enteropathogenic motile Aeromonas in aquatic environment.

A year-long survey on the distribution of motile Aeromonas species in the surface waters of riverine and marine environments was conducted. The filtered membranes were directly placed onto the modified Pril-xylose-ampicillin agar for the enumeration of Aeromonas species. High counts of motile aromonads were found in riverine stations and this bacterial population was also observed in significant quantities in polluted marine samples. In the identification of 2,444 isolates, three species of motile Aeromonas were observed. A. caviae (43%) was prevalent followed by A. sobria (35%) and A. hydrophila (20%). A. hydrophila was high in clean riverine samples, A. sobria was predominantly isolated from a stagnant water sampling area, and A. caviae was distributed more in marine samples. Statistical analyses suggested that the densities of Aeromonas were related to the cumulative effect of various physicochemical parameters rather than to a single factor. Among the species of Aeromonas, A. hydrophila, and A. sobria were highly hemolytic whereas only 11% of A. caviae were observed to lyse sheep erythrocytes. Suckling-mouse assay was performed to elucidate the enterotoxicity of motile aeromonads and 21% of the tested strains (one A. caviae strain) were found to produce enterotoxin.

Aeromonas↗

Characterization of plasmids that confer inducible resistance to 14-membered macrolides and streptogramin type B antibiotics in Staphylococcus aureus.

During a period from 1978 to 1989, 413 Staphylococcus aureus strains were isolated at 27 different geographical regions in Hungary; they exhibited an inducible resistance to the 14-membered macrolides and streptogramin type B antibiotics, but not to the 16-membered macrolides and lincosamides: this resistance is referred to as PMS resistance phenotype. The isolates were mostly associated with patients suffering from staphylococcal diseases and with hygienic screenings in hospitals and closed communities. They were rarely isolated from food-poisoning cases, food hygienic screenings, or animal sources. Strains with PMS resistance phenotype were resistant to penicillin (99.0%), tetracycline (78.7%), and chloramphenicol (63.0%); however, they were susceptible to oxacillin. Most of them (94.2%) belonged to the phage type 52-complex. The determinant for PMS phenotype was located on plasmids, which also encoded beta-lactamase production and cadmium ion resistance, but not arsenate resistance. Three types of plasmid with molecular size of 50 kilobases (kb), 23.8 kb, and 16.8 kb, were found among the strains with PMS resistance phenotype, and the 50 kb and 23.8 kb plasmids also encoded mercury resistance. The 16.8 kb and 23.8 kb plasmids belonged to incompatibility group 1.

Anti-Bacterial Agents↗

Metabolism and toxicity of electroporated 1-beta-D-arabinofuranosylcytosine triphosphate in a human leukemia cell line.

The metabolism and toxicity of 1-beta-D-arabinofuranosylcytosine triphosphate (ara-CTP) directly injected into cells by electroporation was studied in human leukemia cell lines. The intracellular accumulation of ara-CTP (ara-CTP-Ep) was dependent on the cell type, extracellular ara-CTP concentration and pulse voltage on electroporation. In a promyelocytic leukemia cell line, HL-60, ara-CTP-Ep revealed a cytotoxic effect in a dose-dependent manner, although electroporation alone did not have any significant toxicity. Furthermore, simultaneous injection of dCTP, or continuous exposure to deoxycytidine, but not to other deoxyribonucleosides, immediately after electroporation rescued the cells from the toxicity of ara-CTP-Ep. The degradation of ara-CTP-Ep consisted of an early rapid phase followed by a slower phase with a half life of 1.5 h. The addition of dipyridamole (10 microM), an inhibitor of nucleoside transport, retarded this degradation process. These data indicate that transfer of ara-CTP by electroporation is a useful method for the study of ara-CTP metabolism.

Arabinofuranosylcytosine Triphosphate↗

Pathology of soft tissue sarcomas. Selected current issues.

Soft tissue sarcomas are a heterogeneous group of malignant tumors with a wide range of clinical presentation, morphologic features and biologic behavior. During the past two decades, many acceptable new entities have been proposed, and the diagnosis and classification of these tumors have been modified. This paper reviews several current issues that are considered worthy of note for the histologic diagnosis of soft tissue sarcomas.

Humans↗

Alterations of responsiveness to adrenoceptor agonists and calcium of non-infarcted hypertrophied muscles from rats with chronic myocardial infarction.

1. The responsiveness of hypertrophied right ventricular muscle from rats with chronic myocardial infarction (MI) was examined. Myocardial infarction was produced by ligating the left coronary artery. The positive inotropic effects of alpha- and beta-adrenoceptor agonists and calcium on the isolated non-ischaemic muscles were determined at one and four weeks after ligation, and were compared with those in sham-operated (SO) rats. 2. The contractile force of electrically-driven right ventricular papillary muscles was measured isometrically. We also determined the change of beating rate of the right atrium in response to a beta-adrenoceptor agonist. 3. Basal contractile force increased at four weeks after ligation. 4. The pEC50 values of the alpha 1-adrenoceptor agonist, methoxamine, and calcium increased at four weeks after ligation, but the pEC50 values of the beta-adrenoceptor agonist, dobutamine did not change. 5. Maximal contractile force did not change with these agonists at either one and four weeks after ligation. 6. Tissues from rats four weeks after MI exhibited slight increases in the Bmax of alpha- but not beta-receptors, without any changes of affinity. 7. The increases in the sensitivity to an alpha 1-adrenoceptor agonist and calcium may be compensatory mechanisms of non-infarcted ventricular tissue which has undergone hypertrophy in chronic MI.

Adrenergic alpha-Agonists↗

Prostaglandin H2 may be the endothelium-derived contracting factor released by acetylcholine in the aorta of the rat.

The present experiment was performed to identify endothelium-derived contracting factor produced by acetylcholine stimulation in the aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The rings of the thoracic aorta were obtained from age-matched SHR and WKY rats, and changes in isometric tension were recorded. The relaxant responses to acetylcholine in the aortic rings from SHR were significantly weaker than those from WKY rats. The relaxant responses to acetylcholine were significantly enhanced by pretreatment with a cyclooxygenase inhibitor (indomethacin) or thromboxane A2/prostaglandin H2 receptor antagonist (ONO-3708) in aortic rings from both SHR and WKY rats. A thromboxane A2 synthetase inhibitor (OKY-046) did not affect the acetylcholine-induced relaxation in the aortic rings from SHR or WKY rats. In the organ bath solution, after acetylcholine stimulation, prostaglandin E2 and 6-keto-prostaglandin F1 alpha concentrations increased but not prostaglandin F2 alpha and thromboxane B2 concentrations. Exogenous prostaglandin H2, a stable analogue of thromboxane A2, and prostaglandin F2 alpha induced contractions of the SHR rings at a lower concentration than prostaglandin E2, prostaglandin D2, and prostaglandin I2. These contractile responses to various prostaglandins were markedly inhibited by pretreatment with ONO-3708. A prostacyclin synthetase inhibitor did not affect the relaxant responses to acetylcholine in the SHR rings. These results show that endothelium-derived contracting factor is produced and released by acetylcholine stimulation not only in the aorta of SHR but also in those of WKY rats and suggest that prostaglandin H2, a precursor of the released prostaglandins, is a strong candidate for endothelium-derived contracting factor produced by acetylcholine stimulation.

Acetylcholine↗

1,2-diacylglycerol content in thoracic aorta of spontaneously hypertensive rats.

Phosphoinositide metabolism participates in the control of cell calcium homeostasis. Because a notable neutral lipid (1,2-diacylglycerol) is generated from phosphoinositide hydrolysis and is assumed to be a secondary messenger, we determined 1,2-diacylglycerol content and its fatty acid profiles in the thoracic aorta of spontaneously hypertensive rats (SHR) and compared it with those of normotensive Wistar-Kyoto (WKY) rats. After the aorta was exposed to 10(-5) M norepinephrine as a stimulant, 1,2-diacylglycerol content in SHR was significantly higher by 33% than in WKY rats at 4 weeks of age, whereas there was no difference in 1,2-diacylglycerol content between the two strains at 20 weeks of age. Before norepinephrine stimulation, there was no significant difference in 1,2-diacylglycerol level between the two strains at 4 weeks of age. Analysis on a gas chromatograph showed that 1,2-diacylglycerol was composed of similar molecular species of fatty acids in aortas obtained from SHR and WKY rats. On the other hand, the cholesterol content of aortas was higher in SHR than in WKY rats at 20 weeks of age, whereas the difference at 4 weeks was not significant. Phosphatidylcholine, phosphatidylethanolamine, and triglyceride showed no significant difference between the two strains. It is concluded that norepinephrine-induced 1,2-diacylglycerol production increases in the thoracic aorta of SHR before the development of hypertension.

Animals↗