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Biomedical subjects

Y Masuda

Publications and source records attributed to Y Masuda.

At least 415 records · Page 23Linked to original sources
PubMed1994

Effects of the potassium channel openers cromakalim and pinacidil on catecholamine secretion and calcium mobilization in cultured bovine adrenal chromaffin cells.

The effects of two K+ channel openers, cromakalim and pinacidil, on voltage-dependent and receptor-mediated catecholamine secretion and Ca2+ mobilization in bovine adrenal chromaffin cells were studied to determine the role of membrane K+ channels in the regulation of a Ca(2+)-dependent secretory process. Both cromakalim and pinacidil stimulated the efflux of 86Rb (used to monitor K+ permeability) from preloaded cells. Cromakalim and pinacidil did not affect the catecholamine secretion induced by excessive depolarization with 56 mM K+, but inhibited that induced by moderate depolarization with 31 mM K+ in a concentration-dependent manner (1 microM-100 microM). The 31 mM K(+)-induced 45Ca2+ influx and increase in intracellular free Ca2+ concentration [Ca2+]i were also inhibited by these agents at similar concentrations to those for inhibition of catecholamine secretion. Cromakalim and pinacidil inhibited catecholamine secretion, 45Ca2+ influx and increase in [Ca2+]i induced by stimulation of nicotinic acetylcholine (ACh) receptors with carbamylcholine. Furthermore, both cromakalim and pinacidil inhibited the increase in [Ca2+]i induced by carbamylcholine in the absence of extracellular Ca2+, which is thought to be mediated by muscarinic ACh receptors. On the other hand, they did not affect catecholamine secretion induced by Bay-K 8644, Ba2+, A23187, histamine or bradykinin. These results indicate that the K+ channel openers, cromakalim and pinacidil, selectively inhibit catecholamine secretion induced by moderate depolarization or by nicotinic ACh receptor stimulation by inhibiting Ca2+ influx and increase in [Ca2+]i. Furthermore, the results suggest that these K+ channel openers-sensitive membrane K+ channels are involved in the regulation of catecholamine secretion mainly indirectly through effects on the voltage-dependent membrane Ca2+ channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Cyclic hexapeptide endothelin receptor antagonists highly potent for both receptor subtypes ETA and ETB.

A cyclic hexapeptide, cyclo(-D-Asp-Trp-Asp-D-Leu-Leu-D-Trp-), designed from cyclo(-D-Glu-Ala-D-alloisoleucyl-Leu-D-Trp-), an ETA receptor-selective antagonist, possessed not only affinity similar to that of BQ-123 for ETA but also higher affinity for ETB than BQ-123. Further modification led to the discovery of cyclo(-D-Asp-Asp(Php)-Asp-D-Thg-Leu-D-Trp-) (Asp(Php): 1-beta-aspartyl-4-phenylpiperazine; Thg: 2-(2-thienyl)glycine) that inhibited [125I]ET-1 binding to the ETA and ETB receptors with IC50 values of 0.082 nM and 120 nM, respectively. Although this compound possesses 1470-fold less affinity for ETB than for ETA, it behaves as a non-selective antagonist that equipotently inhibits vasoconstriction mediated by both receptor subtypes ETA and ETB.

Amino Acid Sequence↗
PubMed1994

Calcium efflux from cultured bovine adrenal chromaffin cells induced by bradykinin.

The effect of bradykinin on Ca2+ efflux from cultured bovine adrenal chromaffin cells was examined. Bradykinin enhanced the efflux of 45Ca2+ from the cells in a concentration dependent manner (10(-9)-10(-6) M). This effect was inhibited by a specific bradykinin B2-receptor antagonist, but not by a B1-receptor antagonist. Nifedipine, Co2+ and Cd2+ did not inhibit the bradykinin-stimulated 45Ca2+ efflux from the cells. 12-O-Tetradecanoyl phorbol 13-acetate, an activator of protein kinase C, also had no effect on the efflux of 45Ca2+ from the cells. The increase in bradykinin-stimulated 45Ca2+ efflux was reduced by removal of extracellular Na+. These results suggest that bradykinin stimulates Na+/Ca2+ exchange in cultured bovine adrenal chromaffin cells.

Acetylcholine↗
PubMed1994

Primary central nervous system lymphomas. Immunophenotypic, virologic, and cytogenetic findings of three patients without immune defects.

BACKGROUND: Primary central nervous system (PCNS) lymphoma is a relatively rare disease, but an increasing incidence is reported. The Epstein-Barr virus (EBV), which is often found in lymphomas of immunocompromised patients, has been implicated in the development of lymphomas. Many cytogenetic analyses of nodal B cell lymphomas have been performed, but few studies on PCNS lymphomas have been reported. METHODS: The detection of EBV genome using the polymerase chain reaction (PCR) method and cytogenetic studies were performed, in addition to histopathologic and immunophenotypic approaches in biopsied tissue from three patients with PCNS lymphoma. Immunosuppressive states and exposure to mutagens were not clear in all patients. RESULTS: Histopathologic examination disclosed a diffuse type of malignant lymphoma in all patients. Immunophenotypic studies revealed B cell phenotype in all patients, two of whom showed positive reaction for CD5. The PCR method revealed no involvement of EBV genome in tumors in any patients. The cytogenetic study showed clonal chromosome abnormalities in all patients, and abnormalities of chromosome 1 (1q21), 6 (-6, 6q15 and 6q21), 7 (-7 and 7p15), and 14 (14q24 and 14q32) were prominent. The t(6;14)(q15;q32) observed in Patient 1 is the first case to be reported in human de novo lymphoma. CONCLUSIONS: These findings indicate that the causative role of EBV in PCNS lymphoma without immune defects is not clear. The cytogenetic findings were similar to those observed in nodal B-cell lymphoma, suggesting that the origin of PCNS lymphoma cells does not differ from nodal B cell lymphoma cells cytogenetically.

Aged↗
PubMed1994

Prognostic significance of in vitro thymidine uptake in patients with colorectal carcinoma.

In 127 patients with colorectal carcinoma, we measured thymidine uptake by tumor cells cultured in a semisolid medium and compared the influence of various parameters on survival by univariate and multivariate analysis. Fifty-four of the 127 carcinomas (42.5%) incorporated > 1,000 cpm of tritiated thymidine per culture dish and were designated as the high-uptake group, while the other tumors (57.5%, 73/127) were designated as the low-uptake group. There was no significant correlation between high or low thymidine uptake and most of the clinicopathological characteristics of the patients. Patients in the high-uptake had a poor prognosis and a 7-year survival rate of 32.6%, which was significantly different from the rate of 69.3% in the low-uptake group (P < 0.0005). Multivariate analysis showed that thymidine uptake was one of the variables strongly associated with survival in our study population. Thus, it is concluded that thymidine uptake by tumor cells has a high capacity of predicting prognosis, independent of its relationship to other variables. Furthermore, it seems to us that thymidine uptake can help in selecting those patients with colorectal carcinoma who are most likely to benefit from perioperative adjuvant therapy.

Adenocarcinoma↗
PubMed1994

Human papillomavirus type 16 DNA detected by the polymerase chain reaction in non-cancer tissues of the head and neck.

Cancer-free tissues from various anatomical subsites in the head and neck were examined by the polymerase chain reaction (PCR) for the incidence of human papillomavirus (HPV) types 16 and 18. We detected HPV-16 DNA in 9 of 103 samples (8.7%), including specimens from the paranasal sinuses, tonsil, hypopharynx and larynx. However, no HPV-16/18 DNA was detected by Southern hybridization in these 9 samples. The significance of the presence of HPV-16 DNA in non-cancer tissues is still unknown, but PCR detection only of high-risk HPV DNA in head and neck cancer should be evaluated cautiously because of its ubiquity in this region.

Adolescent↗
PubMed1994

Genetic changes in atypical hyperplasia and lymphoma with angioimmunoblastic lymphadenopathy and dysproteinaemia in the same patients.

The transition between atypical hyperplasia and lymphoma with angioimmunoblastic lymphadenopathy and dysproteinaemia (AILD) was studied in serial lymph node biopsy specimens from five patients using DNA analysis with Southern blot analysis, polymerase chain reaction, chromosomal analysis, and immunophenotyping. The chromosomal analysis showed additional abnormalities as the disease progressed to those present initially, and immunological staining showed a corresponding increase in the numbers of CD4- and Ki67-positive cells. In the first biopsy from each patient a diagnosis of atypical hyperplasia with AILD was made and lymphoma excluding by the finding of only a few atypical lymphoid cells and the preservation of follicles with germinal centres. DNA analysis of lymph nodes at this stage showed either germ lines or oligoclonal rearrangements of the T-cell receptor (TCR) and immunoglobulin heavy chain genes. In the final biopsy, when a diagnosis of lymphoma with AILD was made, either a monoclonal rearrangement of the TCR was observed or one of the rearranged bands had increased in density. These results suggest selective proliferation of a clone of abnormal cells may account for the progression of atypical hyperplasia to lymphoma with AILD.

Base Sequence↗
PubMed1994

Expression of human T-cell leukaemia virus type I and associated antigens, and interleukin-2 and receptor in lymph nodes of adult T-cell leukaemia/lymphoma.

To examine the relationship between the expression of human T-cell leukaemia virus type (HTLV-I) mRNA and associated antigens and clinicopathological features, we studied 31 lymph nodes of patients with adult T-cell leukaemia/lymphoma (ATLL) and related diseases, using in situ hybridization and immunohistochemistry. We classified the patients into four types on the basis of their clinicopathological features (HTLV-I associated lymphadenitis, incipient ATLL, ATLL with complete HTLV-I provirus, and ATLL with defective HTLV-I provirus. The expression of HTLV-I mRNA was detected in all 3 patients with incipient ATLL, in 5 of 10 patients with defective-provirus ATLL, in 5 of 11 patients with complete-provirus ATLL, and 3 of 7 with HTLV-I associated lymphadenitis, but the amounts were very small; approximately 1 in 10000-200000 lymph node cells express the viral genomes. This suggests that expression of viral genomes may not be important for immortalization, but it is important that to note the capacity for HTLV-I infection is preserved in each group of non-neoplastic and neoplastic states. HTLV-I mRNA was detected only in lymphocytes and/or lymphoma cells, but the HTLV-I associated antigens (env, gag and pX) were found in histiocytes and endothelial cells, as well as in lymphocytes and/or lymphoma cells. Anti-interleukin 2 receptor (IL-2R) antibody reacted with the giant cells of incipient ATLL and with the transformed lymphocytes and immunoblast-like cells of the HTLV-I-associated lymphadenitis but not with the lymphocytes in the background. Of the typical ATLL, IL-2R was found in both lymphoma cells and giant cells. IL-2 was rarely detected.

Adult↗
PubMed1994

Tubular dilatation in the repair process of ischaemic tubular necrosis.

To elucidate the mechanisms of renal tubular dilatation in acute tubular necrosis (ATN), morphological findings after 60 min ischaemia were studied in rats. The characteristics of the tubular basement membrane (BM) were also examined. A morphometric analysis of cell proliferation, epithelial cellularity and the circumference of damaged tubules was performed. The ischaemic injury resulted in widespread necrosis of renal tubules at day 1, and the BM of damaged tubules appeared thin. The intensity of the immunohistochemical staining for BM components decreased. The epithelial cell proliferation was particularly active in the early phase. Dilatation of the damaged tubules began at day 2, and the degree of dilatation increased up to day 6. Regenerative epithelial hyperplasia occurred and abnormalities of tubular BM were seen. Epithelial hyperplasia and dilatation of damaged tubules was most prominent at day 6 and the tubular BM was thickened by newly produced BM components. Tubular obstruction was not seen and tubules returned to normal size by day 28. Epithelial hyperplasia and abnormalities of tubular BM disappeared progressively. Regenerative tubular epithelial hyperplasia and abnormalities of tubular BM may play an important role in pathogenesis of tubular dilatation in ATN, and tubular dilatation is not due to tubular obstruction.

Animals↗
PubMed1994

Expression of an endogenous and a heterologous gene in Candida maltosa by using a promoter of a newly-isolated phosphoglycerate kinase (PGK) gene.

A gene encoding phosphoglycerate kinase (PGK) was isolated from the genomic library of C. maltosa to construct an expression vector for this yeast. The PGK gene had an open reading frame of 1,251 base pairs encoding approximately 47-kDa polypeptide of 417 amino-acid residues. Expression of this gene assayed by Northern-blot analysis was significantly induced in cells grown on glucose but not in cells grown on n-tetradecane, n-tetradecanol, or oleic acid. By using the promoter region of this gene, an expression vector (termed pMEA1) for C. maltosa was constructed and expression of an endogenous gene (P450alk1 encoding one of cytochrome P450s for n-alkane hydroxylation in C. maltosa) and a heterologous gene (LAC4 encoding Kluyveromyces lactis beta-galactosidase) was tested. Expression of P450alk1 gene was confirmed at both mRNA and protein levels. LAC4 gene expression was confirmed by determining beta-galactosidase activity. The activity in cells grown on various carbon sources correlated very well with the expression levels of PGK mRNA in these cells.

Alkanes↗
PubMed1994

Effects of nefiracetam on deficits in active avoidance response and hippocampal cholinergic and monoaminergic dysfunctions induced by AF64A in mice.

The effects of nefiracetam [DM-9384; N-(2,6-dimethyl-phenyl)-2-(2-oxo-pyrrolidinyl)acetamide] and of phosphatidylcholine on a step-up active avoidance response, locomotor activities and regional brain cholinergic and monoaminergic neurotransmitters in AF64A-treated mice were investigated. Intracerebroventricular (i.c.v.) injection of AF64A (ethylcholine mustard aziridinium ion; 8 nmol/ventricle) impaired acquisition and retention of the avoidance task, and increased vertical and horizontal locomotor activities. Regional levels of acetylcholine, noradrenaline, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were significantly decreased and homovanillic acid (HVA) levels were increased in the hippocampus but not in the septum, cerebral cortex or striatum of AF64A-treated animals. Administration of nefiracetam (3 mg/kg, p.o.) twice daily for 9 days to AF64A-treated animals ameliorated the deficit in active avoidance response in addition to attenuating the increase in locomotor activities. In parallel with these behavioural effects, nefiracetam reversed AF64A-induced alterations in the hippocampal profiles of cholinergic and monoaminergic neurotransmitters and their metabolites. In contrast, administration of phosphatidylcholine (30 mg/kg, p.o.) twice daily for 9 days had no significant effect on the deficit in active avoidance response, despite significantly reversing the decrease in acetylcholine levels in the hippocampus. These results indicate that the effects of nefiracetam on AF64A-induced behavioural deficits are probably due to its ability to facilitate both cholinergic and monoaminergic neurotransmitter systems.

Acetylcholine↗
PubMed1994

MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice.

The effects of acute and chronic administration of MKC-231, a new choline uptake enhancer, and two other nootropic agents, linopiridine (Dup 996) and tetrahydroaminoacridine (THA) on working memory deficits and decreased hippocampal acetylcholine (ACh) content were studied in a delayed non-matching to sample task, using a T-maze, in ethylcholine aziridinium ion (AF64A)-treated mice. Treatment with AF64A (3.5 nmol, i.c.v.) produced memory deficits and decreased hippocampal ACh content. In acute behavioral experiments, MKC-231 and THA had no significant effect on AF64A-induced memory deficits at any doses tested (0.3, 1.0 and 3.0 mg/kg), whereas Dup 996, at a dose of 1.0 mg/kg, significantly improved memory deficits. In chronic experiments, MKC-231 improved memory deficit at all doses tested (0.3, 1.0, or 3.0 mg/kg p.o., once daily for 11 days) and Dup 996 did so only at a dose of 3.0 mg/kg, whereas THA did not improve memory deficit at any doses tested. In acute neurochemical experiments, MKC-231 and THA did not reverse the AF64A-induced hippocampal ACh depletion. Dup 996, however, further decreased hippocampal ACh content compared to that in the AF64A-treated group. In chronic experiments, MKC-231 significantly reversed hippocampal ACh depletion at doses of 0.3 and 1.0 mg/kg, whereas neither Dup 996 nor THA reversed hippocampal ACh depletion at any doses tested. These results indicate that MKC-231 improved the AF64A-induced working memory deficit and hippocampal ACh depletion, probably by recovering reduced high-affinity choline uptake and ACh release.

Acetylcholine↗
PubMed1994

Progression and regression of atherosclerotic findings in the descending thoracic aorta detected by enhanced computed tomography.

Reports evaluating the progression and regression of atherosclerosis by non-invasive procedure are still limited. We investigated the progression and regression of atherosclerotic intimal thickening of the descending thoracic aorta non-invasively measured by enhanced computed tomography in 83 patients (average age 51.0 years) at the beginning and end of a 2.5 year period. The patients were not taking anti-hypertensive, lipid-lowering or hypoglycemic drugs and therefore we consider them as a natural history cohort. At entry, the extent of aortic intimal thickening was 35.2% of the circumference of the cross-section of the wall, which increased to 39.7% after 2.5 years. Spontaneous progression was associated directly with age, elevated levels of total cholesterol, LDL-cholesterol, LDL/HDL cholesterol ratio, diastolic blood pressure, and inversely to HDL-cholesterol. There was little correlation with triglycerides, systolic blood pressure, fasting glucose or body mass index. In 65 of the patients, aortic atherosclerosis progressed, while in 9 patients it remained unchanged, and in a further 9 it regressed. The levels of lipid variables, apart from HDL-cholesterol, and diastolic blood pressure in the patients with spontaneous progression were significantly higher than in the unchanged and spontaneous regression. Thus, this study verified the natural history of aortic atherosclerosis non-invasively measured by enhanced CT.

Adult↗
PubMed1994

Participation of opioid receptor types on post-tetanic twitch inhibition in isolated guinea-pig ileal longitudinal muscle.

The participation of opioid receptor types in the inhibition of the twitch (0.1 Hz, 0.5 msec duration, maximum intensity) following high frequency stimulation (10 Hz, 0.5 msec duration, maximum intensity for 1 min) (post-tetanic twitch inhibition) was investigated in isolated guinea-pig ileal longitudinal muscle using highly selective mu, kappa and delta opioid receptor antagonists. The mu antagonist, beta-funaltrexamine (beta-FNA), produced a concentration-dependent twitch inhibition, which disappeared with thorough washing. The concentration-response curve of the twitch inhibition for morphine was shifted rightward about 10-20-fold by beta-FNA pre-exposure, whereas that for dynorphin 1-13 inhibition remained unchanged. However, after thorough washing of beta-FNA the twitch inhibition of morphine continued during the post-tetanic twitch inhibition for as long as it was tested. The post-tetanic twitch inhibition was partially antagonized by beta-FNA pretreatment and further antagonized by additional exposure to naloxone (NLX). In the presence of nor-binaltorphimine (nor-BNI), a kappa antagonist, which has no effect on the twitch inhibition of morphine, the concentration-response curve of the twitch inhibition of dynorphin 1-13 was shifted rightward approx 100-fold. The post-tetanic twitch inhibition was antagonized by nor-BNI, and no further antagonism was produced by NLX. (Allyl)2-Tyr-Aib-Aib-Phe-Leu (ICI 174,864), a delta antagonist, did not affect the post-tetanic twitch inhibition. These results suggest that both mu and kappa opioid receptors participate in post-tetanic twitch inhibition in isolated guinea-pig ileal myenteric plexus-longitudinal muscle (MPLM).

Amino Acid Sequence↗
PubMed1994

Radial arm maze behavior in mice when a return to the home cage serves as the reinforcer.

Male ddY mice were housed in a cage with an eight arm radial maze apparatus for 6 h a day. A water bottle was placed at the central platform. The end of each arm ran to the home cage through a guillotine door (G). Food was placed at the home cage. During the housing in the apparatus, one G was raised and the remaining seven G were lowered. The raised G was changed every 45 min in random order. Mice housed in this apparatus learned efficient strategy to return the home cage by trial and error. When they chose the arm in which the G was lowered on their way to the home cage from the platform, they returned to the platform, then chose a different arm until they were able to enter the home cage. The mice housed in this apparatus mastered the radial maze task on the 7th day. When scopolamine (SCO) was injected, SCO butylbromide had no effect on performance, but SCO hydrobromide (0.2 and 0.4 mg/kg) impaired working memory, dose dependently. These results show that the apparatus is useful for ease in estimating working memory in mice without the use of severe food or water deprivation.

Animals↗
PubMed1994

Effects of efonidipine hydrochloride (NZ-105), a new calcium antagonist, against acute renal failure in rats.

1. We investigated the effect of efonidipine hydrochloride (NZ-105) against acute renal failure (ARF) in male Wistar rats. ARF was produced by ischemia or glycerol. 2. Ischemia-induced ARF was produced by right nephrectomy and clamping of the left renal artery for 60 min, followed by reperfusion. NZ-105 (20 mg/kg) was orally administered twice a day for 3 days before ARF. The plasma creatinine and urea nitrogen concentrations were markedly elevated in the ischemia ARF group on the 1st day, but the elevation was significantly suppressed by NZ-105 treatment. 3. Glycerol-induced ARF was produced by intramuscular injection of 50% (v/v) glycerol (10 ml/kg) in rats which were restricted to drinking water for 24 hr. NZ-105 (20 mg/kg) was orally administered twice a day for 3 days before ARF. NZ-105 significantly attenuated the severe impairment of creatinine and urea nitrogen clearances and the elevated fractional sodium excretion (FENa) caused by ARF. 4. In the kidney homogenate, NZ-105 (10(-6)-10(-4) M) inhibited lipid peroxidation induced by ascorbic acid and Fe or by NADPH and the inhibitory effect of NZ-105 was stronger than alpha-tocopherol, an antioxidant agent. NZ-105 (10(-5)-10(-3) M) showed radical scavenging action against diphenyl-p-picrylhydrazyl and galvinoxyl induced radicals. 5. These findings suggest that NZ-105 prevents the renal damage caused by the two kinds of ARF. Moreover, the inhibitory effects of NZ-105 against lipid peroxidation and radical formation may be one of the mechanisms involved in the prevention of ARF.

Acute Kidney Injury↗
PubMed1994

Renal protective effect of efonidipine hydrochloride (NZ-105), a new calcium antagonist, in spontaneously hypertensive rats.

1. We investigated the renal protective effect of efonidipine hydrochloride (NZ-105) in spontaneously hypertensive rats (SHR). SHR were given a diet containing 0.075% NZ-105 from 8 weeks old for 20 weeks. 2. 24-hr urinary protein excretion in the control SHR (drug-free diet) increased with age (from 77.3 mg/kg/day at 8 weeks old to 385.4 mg/kg/day at 28 weeks old), while that in NZ-105-treated SHR was maintained at almost the same level as that in Wistar-Kyoto rats (WKY), matched control animals throughout the experimental period. 3. The histological changes of the kidney were examined by light microscopy at the end of the treatment period. In control SHR, swelling and hyalinization of glomeruli, dilatation of renal tubules containing hyaline casts and arteriolosclerosis were revealed. The long-term administration of NZ-105 markedly suppressed these changes. 4. The kidney weights and plasma creatinine concentration in control SHR were higher than those in WKY, while they were significantly reduced in NZ-105-treated SHR. The long-term administration of NZ-105 also suppressed the elevation of systolic blood pressure and the increases of plasma renin activity and aldosterone concentration. 5. These findings suggest that NZ-105 inhibits the development of proteinuria and progressive kidney damage in SHR and may become a useful antihypertensive drug with the renal protective effect.

Animals↗