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Biomedical subjects

S Miyazaki

Publications and source records attributed to S Miyazaki.

At least 433 records · Page 24Linked to original sources
PubMed1994

Discriminative stimulus properties of diazepam and the novel anxiolytic agent 1-amino-5-bromouracil in rats.

A stimulus cue of 1-amino-5-bromouracil (ABU, CAS 127984-93-4) was compared with that of diazepam (DZP) using a drug discrimination paradigm in rats. Groups of rats were trained to discriminate DZP (1 mg/kg i.p.) or ABU (20 mg/kg i.p.) from vehicle. Generalization of the cue of the trained drug to pentobarbital was shown in DZP- and ABU-trained rats at a dose of 5 mg/kg. The stimulus cue of ABU showed a tendency to generalize to DZP in ABU-trained rats but generalization of that of DZP to ABU in DZP-trained rats was only partial. Also partial generalization of that of DZP to imipramine and clonidine was found but not to 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) in DZP-trained rats. Full generalization of the stimulus cue of ABU to imipramine and partial generalization of that of ABU to clonidine and 8-OH-DPAT was observed in ABU-trained rats. The results suggest that the discriminative stimulus properties of ABU differ from those of DZP.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Pharmacological profile of the novel putative anxiolytic agent 1-amino-5-bromouracil.

The newly synthesized compound, 1-amino-5-bromouracil (ABU, CAS 127984-93-4), showed unique anxiolytic activity in rats and mice. Its minimum effective dose was 10 mg/kg p.o. in the Geller type conflict test in rats, and it showed anxiolytic activity at a dose of 20 mg/kg i.p. in the Vogel type conflict test in mice. ABU also induced loss of the righting reflex in mice. The ED50, a dose level that induces loss of the righting reflex in 50% of mice, was 86.4 mg/kg p.o. On the other hand, ABU showed only weak activities both potentiating the drug-induced anesthesia and myorelaxing in comparison with diazepam. Furthermore ABU did not show an affinity for benzodiazepine receptor. Thus, the pharmacological profile of ABU is concluded to be different from that of diazepam.

Anesthetics↗
PubMed1994

Effects of anti-allergy drugs on fMet-Leu-Phe-stimulated superoxide generation in human neutrophils.

We examined effects of six oral anti-allergy drugs used to treat bronchial asthma on fMet-Leu-Phe (N-formyl-methionyl-leucyl-phenylalanine)-induced superoxide (O2-) generation and mobilization of intracellular free calcium ([Ca2+]i) in human neutrophils. We also evaluated the direct action of these drugs on NADPH (reduced nicotinamide-adenine dinucleotide phosphate)-oxidase activity in cell lysate (cell-free system). Ketotifen (25 approximately 200 microM) enhanced fMet-Leu-Phe-stimulated O2- generation and [Ca2+]i mobilization, although it directly inhibited NADPH oxidase in the cell-free study. Low concentrations of oxatomide (5-20 microM) enhanced O2- generation, but concentrations > 25 microM inhibited O2- generation. In concentrations below 20 microM, oxatomide had no effects on fMet-Leu-Phe-stimulated [Ca2+]i mobilization, but at concentrations above 25 microM, it inhibited [Ca2+]i mobilization. Oxatomide inhibited NADPH oxidase activity at all concentrations examined. Azelastine, pemirolast, tranilast, and repirinast inhibited O2- generation and [Ca2+]i mobilization. Azelastine and pemirolast directly inhibited NADPH oxidase, but tranilast and repirinast did not. Our results indicated that except for ketotifen and low concentration of oxatomide, oral anti-allergy drugs used to treat bronchial asthma inhibited fMet-Leu-Phe-induced O2- generation in human neutrophils. Based on IC50 values, potency of drugs was as follows: oxatomide > azelastine > tranilast > pemirolast > repirinast.

Adult↗
PubMed1994

1H-NMR analysis of nerve edema in the streptozotocin-induced diabetic rat.

To define the existence of intracellular hydration caused by metabolic derangements in the excised sciatic nerves of diabetic rats quantitatively, relaxation times (T1, T2) and fraction of intracellular water content were measured with 1H-nuclear magnetic resonance (NMR) spectroscopy in normal rats (control group, n = 10), streptozotocin (STZ)-induced (50 mg/kg, i.v.) diabetic rats (DM group, n = 10), STZ-induced diabetic rats treated with an aldose reductase inhibitor (ARI, Epalrestat, 100 mg/kg) (ARI group, n = 8), and STZ-induced diabetic rats treated with insulin (insulin group, n = 4). For selective measurement of intracellular relaxation times, the inversion recovery (IR) method for conventional T1 and Carr-Purcell-Meiboom-Gill method for T2 were used with an aqueous chemical shift reagent, 10 mmol/L dysprosium triethylenetetramine-N,N,N',N",N"',N"'-hexaacetic acid, resulting in distinct separation of intracellular (Schwann cell, axon, endothelial cell, and pericyte) and extracellular waters under the isotonic condition of the rat sciatic nerves. Furthermore, a new method of driven-equilibrium single-pulse observation of T1 (DESPOT) was used for rapid measurement of T1 for the purpose of clinical application on magnetic resonance imaging (MRI). T1 values measured by the DESPOT and IR methods were significantly correlated (p < 0.001). Total and intracellular water contents, sorbitol contents, and relaxation times of the sciatic nerve taken from the DM group were significantly elevated (p < 0.01), while myoinositol (p < 0.01) and extracellular water (p < 0.05) contents were significantly decreased as compared with the control group. Both insulin and ARI treatments significantly improved relaxation times as compared with those in the DM group (p < 0.05-0.01). Relaxation times correlated positively with total water (T1, p < 0.05-0.01; T2, p < 0.01), intracellular water (T1, p < 0.001; T2, p < 0.001), and sorbitol (T1, p < 0.001; T2, p < 0.001) contents of the excised nerve. Sorbitol content correlated positively with total and intracellular water contents (p < 0.01) but negatively with extracellular water content (p < 0.05). These findings indicated that sorbitol itself and/or secondary sodium accumulation caused by an increase in sorbitol may be a major contributor to the increase in intracellular hydration and prolonged relaxation times associated with hyperglycemia, which are reversible with insulin or ARI treatment. It was also suggested that rapid T1 measurement would provide new insights into the pathogenesis of human diabetic neuropathy as a non-invasive evaluation method on MRI.

Aldehyde Reductase↗
PubMed1994

[Clinical trial of protocol-AL851 for children with high-risk acute lymphoblastic leukemia. Kyushu Yamaguchi Children's Cancer Study Group (KYCCSG)].

Fifty five children diagnosed as having high-risk acute lymphoblastic leukemia (ALL) between 1985 and 1988 were treated with protocol AL851. The agents used in the protocol were as follows: induction therapy: vincristine (VCR), prednisolone, daunorubicin (DNR) and l-asparaginase, consolidation therapy: an intermediate-dose methotrexate (MTX), central nervous system (CNS) leukemia prophylaxis: intrathecal MTX and 24Gy cranial irradiation, reinduction therapy: VCR, adriamycin, dexamethasone and high dose cytarabine (AraC), maintenance therapy: 6-mercaptopurine, cyclophosphamide, MTX, DNR, VCR and AraC. Patients received chemotherapy for 3 years after achieving complete remission (CR). CR was obtained in 51 patients (92.7%). Twenty-four of them relapsed after achieving CR (bone marrow 16, CNS 3 and testis 5). At median follow-up of 79 (range 64-102) months, the estimated 8-year disease free survival rate was 49.1 +/- 6.7%. Four patients relapsed at bone marrow during the first 6 months of the treatment, indicating that more intensive combination chemotherapy should be included in earlier stage of the protocol. The high incidence of testicular relapse (14.3% in boys) suggests that high-dose MTX or AraC should be needed for improvement of the prognosis of high-risk ALL patients.

Age Factors↗
PubMed1994

Glomerular nodular lesions in non-amyloid immunoglobulin deposition disease: their pathogenetic relationship to mesangiolysis.

Renal biopsy of a 70-year-old woman with clinical features of rapidly progressive glomerulonephritis revealed nodular glomerulosclerosis with conspicuous crescent formation. Other peculiar findings were the presence of many mesangiolytic cystic lesions and multinucleated giant cells in the cystic lesions. By immunofluorescent microscopic study, lambda light and gamma heavy chains were found in mesangial nodules, Bowman's capsule and the tubular basement membrane. Multiple myeloma was diagnosed by bone marrow examination. Autopsy performed two months later revealed systemic deposition of lambda light and gamma heavy chains, and fairly advanced nodular glomerulosclerosis. Most of the glomerular nodular lesions had a lamellar structure. Amyloid was not found. The high incidence of both mesangiolytic lesions in the biopsy specimen and laminated glomerular nodules in the autopsy material supports the previously proposed pathogenetic relationship of these two findings.

Aged↗
PubMed1994

[The etiology and clinical features of hemolytic uremic syndrome].

The incidence of hemolytic uremic syndrome (HUS) has been increased for these several years. As the cause of HUS, verotoxin-producing E coli (VTEC) is very important. By our nationwide survey for five years from 1986 to 1990, 146 cases with HUS were compiled. Among 122 cases of HUS, 101 cases (82.8%) had good prognosis, 15 cases (12.3%) had renal or CNS residue. And death rate was 4.9% (6 cases). Clinical features were compared between the groups of good and poor prognosis. In the group of poor prognosis, impaired consciousness, convulsion and hypertension were significantly high. The data of biochemistry such as BUN, creatinine, GOT, GPT, C3, CH50 and CRP were significant between two groups. Demonstration of VTEC and positive serum antibody were seen in 60% among 35 cases. Dr Takeda of National Children's Hospital estimates that the incidence of hemolytic colitis is 1200 cases per year, and the occurrence of HUS is about 100 cases per year, among them 70% cases may be caused by VTEC.

Adult↗
PubMed1994

[Successful treatment of acute myelogenous leukemia in an elderly patient with cytarabine ocfosfate].

A 77-year-old female with left hemiplegia caused by cerebral infarction and with mild senile dementia was admitted for further examination of hematological abnormalities. She was diagnosed as acute myelogenous leukemia (AML-M5a) according to French-American-British classification. Since intensive combination chemotherapy seemed difficult, she was treated with oral administration of cytarabine ocfosfate (200 mg/day, for 14 days), a cytidine deaminase-resistant derivative of Ara-C, resulting in complete remission. Major side effects were nausea, vomiting and appetite loss, but their incidences were reduced tolerably when cytarabine ocfosfate was given just before sleeping. Cytarabine ocfosfate might be useful to treat AML in elderly patients having certain complications such as cerebrovascular disease.

Administration, Oral↗
PubMed1993

Increase in plasma concentration of ubiquitin in dialysis patients: possible involvement in beta 2-microglobulin amyloidosis.

beta 2-Microglobulin(beta 2-M) amyloidosis is a serious complication of dialysis therapy; however, its pathogenesis is still unclear. Recent studies have indicated that ubiquitin has amyloid enhancing factor activity, raising the possibility that ubiquitin plays a role in beta 2-M amyloidogenesis. In this study, synovial tissue from patients with long-term dialysis was examined immunohistochemically. The synovial tissue was labeled with anti-ubiquitin antibody, indicating co-deposition of ubiquitin with beta 2-M amyloid. To elucidate the involvement of plasma ubiquitin, we established a specific radioimmunoassay for ubiquitin. Using this method, we observed that the plasma concentration of ubiquitin-like immunoreactivity in dialysis patients was significantly higher than that in normal subjects. In chronic renal failure patients, the plasma concentration of ubiquitin-like immunoreactivity was also significantly higher than that in normal controls, which finding suggests that a reduction in renal clearance is, at least in part, responsible for the increased plasma concentration of ubiquitin. In dialysis patients, plasma concentrations of ubiquitin-like immunoreactivity in patients with carpal tunnel syndrome, one of the major symptoms of beta 2-M amyloidosis, were significantly higher than those in patients not exhibiting this syndrome. These results suggest a possible involvement of plasma ubiquitin in beta 2-M amyloidosis.

Amyloidosis↗
PubMed1993

Ca2+ response in single human T cells induced by stimulation of CD4 or CD8 and interference with CD3 stimulation.

A Ca2+ imaging method has been used to demonstrate simultaneously the magnitude and time course of the increase in the intracellular Ca2+ concentration ([Ca2+]i) in 10-30 individual human peripheral T cells following stimulation by anti-CD4 or anti-CD8 monoclonal antibody (MAb) as well as anti-CD3 MAb. The rise in [Ca2+]i began within 10 s of the introduction of the MAb and reached a peak of 240 nM (mean of 73 cells) in 20-40 s. The peak was followed by a slow decrease persisting for 6-8 min. Comparing Ca2+ responses in the presence and absence of external Ca2+, the rise in [Ca2+]i was found to be caused by both transient intracellular Ca2+ release and a long-lasting Ca2+ influx from outside the cell. Cross-linking of CD4 or CD8 using anti-IgG antibody augmented the response in individual cells, as seen in the higher peak (365-390 nM) and the longer duration (over 10 min). Simultaneous stimulation of CD3 and CD4 did not cause a summation of Ca2+ responses but caused a suppression in the CD3-mediated Ca2+ response. The results support the view that CD4 and CD8 play a role in signal transduction for T cell activation and that the CD4-derived signal interferes with the CD3-derived signal at some stage in the signalling pathway causing the Ca2+ response.

Antibodies, Monoclonal↗
PubMed1993

Post-ischemic potentiation of Schaffer collateral/CA1 pyramidal cell responses of the rat hippocampus in vivo: involvement of N-methyl-D-aspartate receptors.

The present study examined the functional changes in the hippocampal CA1 pyramidal cell system in vivo occurring after 12-min forebrain ischemia in the rat. A population excitatory postsynaptic potential and orthodromic population spike of CA1 pyramidal cells to stimulation of the Schaffer collaterals were potentiated at 6-8 h post-ischemia. These changes were not associated with an increase in excitability of the CA1 pyramidal cells as evaluated from the antidromic population spike induced by alveus stimulation, suggesting the presence of an increased synaptic efficacy. The post-ischemic potentiation was prevented by pretreatment with the N-methyl D-aspartate (NMDA) receptor antagonist, MK801, in a dose-dependent manner. These findings suggest that 12-min forebrain ischemia in the rat activates NMDA receptors, which results in an increase in synaptic efficacy to the CA1 pyramidal cells at 6-8 h post-ischemia.

Animals↗
PubMed1993

Immunochemical characterization of anti-H monoclonal antibodies obtained from a mouse immunized with human saliva.

Three IgM class anti-H monoclonal antibodies (1E3, 1E5 and 3H1) were obtained from a BALB/c mouse immunized with human O type saliva. These antibodies were found to agglutinate red cells from O group and A and B subgroups but not from Bombay and para-Bombay individuals whose H antigen was barely detected by anti-H reagents. The agglutination reactions of these antibodies were inhibited by H antigens from human tissues. It was also demonstrated that both 1E3 and 3H1 reacted with H disaccharide (Fuc alpha 1-->2Gal beta), H type 1 (Fuc alpha 1-->2Gal beta 1-->3GlcNAc beta), H type 2 (Fuc alpha 1-->2Gal beta 1-->4GlcNAc beta), H type 3 (Fuc alpha 1-->2Gal beta 1-->3GalNAc alpha) and H type 4 (Fuc alpha 1-->2Gal beta 1-->3GalNAc beta) but not with Lea (Gal beta 1-->3[Fuc alpha 1-->4]GlcNAc beta), Leb (Fuc alpha 1-->2Gal beta 1-->3[Fuc alpha 1-->4]GlcNAc beta), X (Gal beta 1-->4[Fuc alpha-->3]GlcNAc beta) or Y (Fuc alpha 1-->2Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc beta). On the other hand, 1E5 was found to react with H type 1, H type 2, Leb and Y. Because of the unique reactivities against various fucosyl linkages these monoclonal antibodies could be useful not only as anti-H reagents but also as reagents for the structural analysis of fucosylated glycoconjugates.

ABO Blood-Group System↗
PubMed1993

Development of inositol trisphosphate-induced calcium release mechanism during maturation of hamster oocytes.

Mature hamster eggs exhibit repetitive increases in the intracellular Ca2+ concentration ([Ca2+]i) at fertilization, caused by inositol 1,4,5-trisphosphate (InsP3)-induced Ca2+ release (IICR) from stores. Oscillating Ca2+ rises also occurred in inseminated immature oocytes at the germinal vesicle (GV) stage but the peak [Ca2+]i of each response was about half of that in mature eggs. Like the responses to sperm in the mature egg, those in the immature oocyte were also blocked by injection of a monoclonal antibody against the InsP3 receptor (18A10). Compared with mature eggs, immature oocytes were more sensitive to externally applied serotonin which caused repetitive IICR, but each response was smaller. The development of the IICR mechanism during oocyte maturation was investigated using iontophoretic injection of InsP3 and Ca2+ imaging with fura 2. In immature oocytes the rise in [Ca2+]i with an InsP3 pulse of 1.2 nA for 1 sec was 35% of that in mature eggs. The response increased with increasing doses of InsP3. The nearly maximum response, obtained with a 20-nA 2-sec pulse, was 80% of that in mature eggs, suggesting that immature oocytes are less sensitive to InsP3 but that most of Ca(2+)-releasable stores are already present in the immature oocyte. IICR developed in two phases during in vivo maturation. The sensitivity to InsP3 increased gradually between the GV stage and prometaphase of the first meiosis. Then a nonlinear dose-response relation developed during the second meiosis to metaphase II, resulting in regenerative, propagating Ca2+ release induced by a threshold pulse of 1 nA for 1 sec in mature eggs. Similar changes occurred during in vitro maturation of oocytes isolated from follicles at GV stage and cultured for up to 16 hr. The development of IICR is thought to be a prerequisite factor for the acquisition of the ability of an egg to undergo normal fertilization.

Animals↗
PubMed1993

Essential role of the inositol 1,4,5-trisphosphate receptor/Ca2+ release channel in Ca2+ waves and Ca2+ oscillations at fertilization of mammalian eggs.

At fertilization mammalian eggs exhibit repetitive rises in the cytoplasmic Ca2+ concentration (Ca2+ oscillations), associated with propagating Ca2+ waves in the initial responses. The Ca2+ oscillation causes cortical granule exocytosis and resumption of second meiosis and affects later embryonic development. Recent studies using a function-blocking monoclonal antibody to the inositol 1,4,5-trisphosphate (InsP3) receptor/Ca2+ release channel demonstrated direct evidence that InsP3-induced Ca2+ release (IICR) from intracellular stores operates at fertilization of the hamster egg and that IICR is essential in the initiation, propagation, and oscillation of the sperm-induced Ca2+ rises. Ca(2+)-induced Ca2+ release (CICR) has also been suggested, but a sensitizing action of Ca2+ on the InsP3 receptor, i.e., Ca(2+)-sensitized IICR, can serve as a regenerative process of Ca2+ release and could be the basis for Ca2+ waves and Ca2+ oscillations. It is now apparent that signal transduction at fertilization is dependent on sperm-stimulated activation of phospholipase C which causes hydrolysis of phosphatidylinositol bisphosphate and production of InsP3, leading to IICR. On the other hand, Ca2+ signaling at fertilization of the sea urchin egg may also involve ryanodine receptor-mediated CICR.

Animals↗
PubMed1993

Effects of indeloxazine on hippocampal CA1 pyramidal cell damage following transient cerebral ischemia in the gerbil.

The effects of indeloxazine on the ischemia-induced death of hippocampal CA1 pyramidal cells following transient cerebral ischemia were examined in the mongolian gerbil. Increased survival of CA1 pyramidal cells was demonstrated in animals pre- and post-treated with indeloxazine. Increased survival of CA1 pyramidal cells was, however, not demonstrated in animals post-treated but not pre-treated with indeloxazine. A previous study has demonstrated that indeloxazine increases the glucose and adenosine triphosphate (ATP) contents in the brain probably through an enhanced capability of oxidative phosphorylation. It has been reported that increases in the glucose and ATP contents in the brain before ischemia delay the onset of massive ionic fluxes during ischemia. The delay in onset of this ionic event may help to protect these cells from death. The present data suggest that energy state before ischemia may play an important role in the protective effect of indeloxazine.

Adenosine Triphosphate↗
PubMed1993

Regulation of 18-oxocortisol and 18-hydroxycortisol by the renin-angiotensin system and ACTH in man.

Based on urinary excretion studies the secretion of the cortisol derivatives, 18-oxocortisol and 18-hydroxycortisol are believed to be regulated by ACTH and to a lesser degree by the renin-angiotensin system. Plasma concentrations of 18-oxocortisol and 18-hydroxycortisol were measured during the simultaneous activation of the renin-angiotensin system and inhibition of ACTH secretion. Five healthy male subjects consuming a sodium diet ad libitum were studied. Blood was drawn at 0800 h after 1 h in the supine position. In the first set of experiments, the subjects remained in the supine position from 0800 to 1000 h with or without the oral administration of 2 mg dexamethasone at 0800 h. In the second set of experiments the subjects were placed in the upright position after drawing the 0800 h sample. The subjects were studied with and without dexamethasone administered at 0800 h. Blood was drawn again at 1000 h. Plasma levels of 18-oxocortisol, 18-hydroxycortisol, ACTH, plasma renin activity (PRA), cortisol, aldosterone and 18-hydroxycorticosterone were measured by radioimmunoassay. None of these parameters changed during the 2 h in the supine position. 18-Oxocortisol, 18-hydroxycortisol, aldosterone, 18-hydroxycorticosterone and PRA increased, but ACTH and cortisol did not change when the subjects were placed in the upright position. After dexamethasone administration, 18-oxocortisol, 18-hydroxycortisol, cortisol, aldosterone and 18-hydroxycorticosterone decreased in the supine position and no increase occurred in 18-oxocortisol, 18-hydroxycortisol and 18-hydroxycorticosterone in the upright position. PRA and aldosterone increased and ACTH and cortisol decreased in these subjects. 18-Oxocortisol and 18-hydroxycortisol were more dependent on ACTH regulation and less on the renin-angiotensin system than aldosterone.

18-Hydroxycorticosterone↗