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Biomedical subjects

S Shinohara

Publications and source records attributed to S Shinohara.

At least 19 recordsLinked to original sources

Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels: a possible involvement of free radicals.

Amyloid beta protein (A beta), the central constituent of senile plaques in Alzheimer's disease (AD) brain, is known to exert toxic effects on cultured neurons. The role of the voltage-sensitive Ca2+ channel (VSCC) in beta (25-35) neurotoxicity was examined using rat cultured cortical and hippocampal neurons. When L-type VSCCs were blocked by application of nimodipine, beta (25-35) neurotoxicity was attenuated, whereas application of omega-conotoxin GVIA (omega-CgTX-GVIA) or omega-agatoxin IVA (omega-Aga-IVA), the blocker for N- or P/Q-type VSCCs, had no effects. Whole-cell patch-clamp studies indicated that the Ca2+ current density of beta (25-35)-treated neurons is about twofold higher than that of control neurons. Also, beta (25-35) increased Ca2+ uptake, which was sensitive to nimodipine. The 2', 7'-dichlorofluorescin diacetate assay showed the ability of beta (25-35) to produce reactive oxygen species. Nimodipine had no effect on the level of free radicals. In contrast, vitamin E, a radical scavenger, reduced the level of free radicals, neurotoxicity, and Ca2+ uptake. These results suggest that beta (25-35) generates free radicals, which in turn, increase Ca2+ influx via the L-type VSCC, thereby inducing neurotoxicity.

Amyloid beta-Peptides

Adverse effects of colophony.

Regarding colophony, the use in industries, adverse effects, diagnosis, pathophysiology and control are reviewed. Colophony is an unhomogeneous mixture of resin acids as like abietic acid and neutral substances. Colophony is used everywhere, in industry, daily life and medical supplies. Soldering workers are exposed to the colophony fumes heated up to the temperature of soldering irons. The effects of exposure to colophony are classified into bronchial asthma and contact dermatitis. Colophony fumes cause bronchial asthma by its nonspecific irritation. Inhalation challenge test and repeated spirometry during working day may help the diagnosis of colophony induced asthma. Improvement of working environment for soldering and development of new flux instead of colophony will be necessary. A study on contact dermatitis revealed that colophony and its related compounds are one of major causes for contact dermatitis. Cases of dermatitis by depilatory agents used to remove hair from slaughtered swine, anti-slipping cream for ballet shoes or resin for cello strings have been reported. Patch test may contribute to the diagnosis of dermatitis caused by colophony.

Asthma

Quasi-steadiness approximation for the single-compartment urea kinetic model (SCUKM).

Using SCUKM, we constructed recurrence formulae expressing weekly pre- and post-dialysis urea levels. Then we mathematically derived simple methods to estimate Kt/V0 and the urea generation rate (G) per unit urea distribution space post-dialysis (V0), which only required the measurement of pre- (C) and post-dialytic blood urea concentrations (C0) of a single hemodialytic session (two-point method). Underlying fundamental assumptions were: (i) patients receive weekly scheduled hemodialysis; (ii) the ultrafiltration rate, intradialytic urea generation, interdialytic water increase rate, and residual renal function are small enough to be retained only as the leading term in the formulae. In the derivation, we proved relations: C = f(Kt/V0)G/V0, and C0 = g(Kt/V0)G/V0, which state that both C and C0 are directly proportional to G/V0, and that the proportional constants are functions of Kt/V0. Errors of the formulae were also checked to make the limitation of the approximations clear. The present formulae exactly reproduced Kt/V0 and G/V0 of virtual patients strictly obeying the SCUKM in a computer simulated model. Using the blood urea nitrogen concentration data of 20 actual patients, we compared our method with the usual three-point method and obtained substantial correlations between them (r = 1.00 for Kt/V0, r = 0.98 for G/V0). Finally, we proposed convenient and easily calculable new formulae, which give sufficiently accurate Kt/V0 and G/V0.

Blood Urea Nitrogen

2-Deoxy-2-fluoro-D-glucose as a functional probe for NMR: the unique metabolism beyond its 6-phosphate.

Epimeric conversion of 2-deoxy-2-fluoro-D-glucose (FDG) to its 2-epimer 2-deoxy-2-fluoro-D-mannose (FDM) proved by 19F NMR has been shown to reflect the brain activity. To examine the feasibility of FDG as a new NMR probe for in vivo functional monitoring, we studied here the fundamental NMR properties of metabolites, spectral assignments, and reliability of NMR quantification. Metabolites confirmed in brain besides FDM-6-phosphate were as follows: FDG-1-phosphate, FDG-1,6-bisphosphate, FDM-1-phosphate, FDM-1,6-bisphosphate, and FDG and FDM derivatives of nucleotide diphosphate. NMR quantification of these metabolites was evaluated in comparison with the method of 18F-labeled FDG. In the NMR functional study using FDG, where a high dose is inevitable, the dose dependence of uptake was investigated. FDG uptake in mouse brain was shown to be in the range of interpretation using the biochemical parameters of enzymes for glucose uptake as long as a dose of < 200 mg/kg was used.

Animals

Sialyl Lewis X analog inhibits eosinophil accumulation and late asthmatic response in a guinea-pig model of asthma.

Preferential eosinophil accumulation is characteristic of airway inflammation in asthma. Although little is known about its mechanism, the effect of a sialyl Lewis X analog on airway eosinophilia was examined in a guinea-pig model of asthma. Guinea-pigs were sensitized by repeated inhalation of ovalbumin. After a single inhalation challenge, the animals showed striking airway eosinophilia and a late asthmatic response. In contrast, when guinea-pigs were pretreated intravenously with sialyl Lewis X analog (LX 0104) 1 h before antigen challenge, both eosinophil infiltration in the tracheal wall and the late asthmatic response were significantly inhibited in a dose-dependent manner. In a further in vitro study, LX 0104 significantly suppressed the adhesion of human and guinea-pig eosinophils to human umbilical vein endothelial cells activated with interleukin-1 beta. These results suggest that LX 0104 plays a critical role in antigen-induced airway eosinophilia and the late asthmatic response.

Animals

Expression of two different cholecystokinin receptors in Xenopus oocytes injected with mRNA from rabbit pancreas and rat hippocampus.

Electrophysiological responses to cholecystokinin (CCK) were studied in Xenopus oocytes injected with mRNA from rabbit pancreas or rat hippocampus. CCK-octapeptide(26-33) (sulfated form) (CCK-8) elicited inward currents in both groups. In oocytes injected with pancreatic mRNA, CCK-8-induced currents were composed of two components, fast and slow. However, in oocytes injected with hippocampal mRNA, fast currents disappeared. The potency ranking of the agonists and the antagonist indicated that the receptors expressed by pancreatic and hippocampal mRNA were CCKA- and CCKB-subtypes, respectively. Extracellular application of EGTA had little effect on the CCKB-mediated response, but attenuated the CCKA-mediated one. Intracellular injection of EGTA abolished the CCKB-mediated response, whereas small smooth currents remained in oocytes expressing the CCKA-receptor. The reversal potentials of the CCKA- and CCKB-receptor-mediated responses were consistent with that for CI- currents. However, the reversal potential of the small smooth currents in EGTA-loaded oocytes expressing the CCKA-receptors was close to that for a non-selective cation channel. These results suggest that CCK-8 activates at least two different channels, a Ca(2+)-dependent Cl- channel and a non-selective cation channel in oocytes expressing the CCKA-receptor, while the CCKB-receptor elicits only a Ca(2+)-dependent Cl- channel.

Animals

Differential expression of Fas antigen and Bcl-2 protein on CD4+ T cells, CD8+ T cells, and monocytes.

Fas antigen and Bcl-2 protein are considered to be involved in cellular homeostasis. We precisely analyzed the expression of human Fas antigen and Bcl-2 protein on CD4+ T cells, CD8+ T cells, and monocytes. The positivities of Fas antigen on CD4+ and CD8+ T cells increased with aging. In CD4+ T cells, the Fas-/CD45RO+ subpopulation was dominant compared with the Fas+/CD45RO- subpopulation. Conversely, in CD8+ T cells, the Fas+/CD45RO- subpopulation was dominant compared with the Fas-/CD45RO+ subpopulation. Monocytes exhibited high positivity of Fas antigen and low fluorescence intensity of Bcl-2 protein compared with T cells. These results suggest that Fas antigen acts in different processes of cellular homeostasis between CD4+ and CD8+ T cells and that expression of Fas antigen and Bcl-2 protein is involved in homeostasis of monocytes as well as lymphocytes.

Adult

Effects of recombinant human erythropoietin and exercise training on exercise capacity in hemodialysis patients.

The effects of recombinant human erythropoietin (rHuEPO) and exercise training on exercise capacity were evaluated in 20 hemodialysis patients. After improvement of anemia by rHuEPO (Phase I), patients were divided into 2 groups. Group 1, 10 patients, was placed in a 3-month exercise training program. Group 2, 10 patients, served as a control group (Phase 2). A symptom-limited exercise tolerance test was performed at the start of Phase 1 and before and after Phase 2. Hemoglobin (Hb) values were kept constant throughout Phase 2. In Phase 1, maximum workloads (62.0 +/- 19.1 to 76.5 +/- 25.6 W, p < 0.001), maximum O2 uptake (VO2max) (18.7 +/- 3.5 to 2.2 +/- 5.9 ml/min/kg, p < 0.01), and VO2 at anaerobic threshold (AT) (VO2AT) (8.5 +/- 2.1 to 10.2 +/- 2.9 ml/min/kg, p < 0.01) were all improved by rHuEPO. However, in Phase 2, despite unchanged Hb values and maximum workloads, VO2max (20.7 +/- 4.6 to 17.6 +/- 2.6 ml/min/kg, p < 0.05) and VO2AT (10.6 +/- 1.4 to 9.5 +/- 1.8, ml/min/kg p < 0.05) were decreased in Group 2. However, in Group 1, maximum workloads (66.7 +/- 8.2 to 81.7 +/- 7.5 W, p < 0.01) were improved, and VO2max and VO2AT were not decreased significantly in the same period. Exercise training in rHuEPO-treated hemodialysis patients resulted in an improved aerobic exercise capacity, whereas those without exercise training did not have increased capacity. Throughout the study, O2 uptakes were lower than those of nonrenal anemic patients who had similar Hb values. Maximum lactate values also remained low. In conclusion, improvement in the exercise capacity in hemodialysis patients treated with rHuEPO was minimal. Some defects were suggested in the aerobic energy production system in skeletal muscle of dialysis patients. Anemia-improved patients should participate in incremental physical activity to maintain an improved exercise capacity.

Adult

Plasmacytoma of the testis.

Extramedullary plasmacytomas of the testes are extremely rare tumors, especially when occurring in the absence of precocious or concurrent diagnosis of multiple myeloma. This is a case report of an 83-year-old man with a solitary plasmacytoma of the left testis. Immunoperoxidase studies, performed on histologic specimens after radical orchiectomy, showed a monoclonal staining of intracellular immunoglobulin for IgG-lambda type. He has been well for more than 14 months with no evidence of local recurrence or multiple myeloma.

Aged

Blood polychlorinated biphenyls and manifestation of symptoms in chronic "Yusho" patients.

The correlation between blood PCB concentration and clinical manifestation of symptoms was investigated in 259 chronic "Yusho" patients, using the information obtained from the nationwide health examination conducted in 1988, twenty years after the outbreak. Concentrations of blood PCBs ranged 0.6-32.0 ppb (mean; 4.78), and they were categorized into approximate quartile for analysis. For general fatigue, odds ratios at 2.7+, 4.1+, and 6.1+ ppb were 2.4, 3.6, and 3.1, respectively, with a reference category of < 2.7 ppb (test for trend; p < 0.005). For numbness in extremities, the corresponding odds ratios were 2.8, 2.8, and 2.9(p < 0.005). For comedone, they were 1.4, 1.0, and 4.0 on face (p < 0.025); and 3.6, 4.6, and 9.5 on trunk (p < 0.005), respectively. A distinctive increase in odds ratio was observed at 2.7 ppb for these two subjective symptoms; and at 6.1 ppb for skin symptoms. The blood PCB concentrations among patients were relatively close to the normal subjects. Therefore, the observed correlations may be due to the effects of PCBs with a peculiar pattern in components, PCQs or PCDFs, taken and retained in the patients. Association with blood PCBs was also suggested for headaches; abnormal breath sounds; and acneiform eruptions in the genital region, but were statistically insignificant. None of the eye symptoms showed significant association with blood PCBs.

Adult

Lipopolysaccharide primes human basophils for enhanced mediator release: requirement for plasma co-factor and CD14.

Lipopolysaccharide (LPS) is known to enhance IgE-mediated basophil degranulation. Recently, the complex of LPS and plasma LPS-binding protein(LBP) has been shown to induce secretory response via CD14 in monocytes and neutrophils. In the current study, we observed that the sensitivity to LPS of basophils was increased to 100-fold by co-incubation with plasma. LPS promptly completed its effect and amplified degranulation by stimuli bypassing IgE-receptors. Treatment with anti-CD14 completely abolished the priming effect of LPS. These results indicate that the priming effect of LPS on basophil mediator release is mediated via CD14, and that plasma co-factor, possibly identical to LBP, potentiates this reaction.

Acute-Phase Proteins

Desensitization of cholecystokininB receptors in GH3 cells.

Desensitization of the cholecystokinin (CCK) octapeptide (CCK-8)-induced rise in intracellular free calcium concentration ([Ca2+]i) was characterized in GH3 cells, a pituitary tumor cell line, which are known to possess CCKB receptor subtype. The CCK-8-induced [Ca2+]i transient was reduced following the initial application of CCK-8. A similar desensitization of the CCK-8-induced response was observed following the first application of thyrotropin-releasing hormone (TRH). By contrast, the TRH-induced response was not desensitized by the preceding application of CCK-8. Desensitization of the CCK-8-induced [Ca2+]i transient was associated with diminished inositol 1,4,5-trisphosphate formation. The recovery of desensitization of the CCK-8-induced response was delayed by a phosphoserine/phosphothreonine phosphatase inhibitor, calyculin A (100 nM). The responsiveness to CCK-8 was also reduced by phorbol 12,13-dibutyrate (PDBu), and this effect of PDBu was completely abolished by preincubation with staurosporine. Staurosporine significantly attenuated the desensitization caused by preincubation with CCK-8, but this effect was too small to attribute the desensitization to the protein kinase C transduction pathway alone. It is likely that desensitization of CCK receptors involves multiple transduction pathways.

Alkaloids