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Biomedical subjects

S Shinohara

Publications and source records attributed to S Shinohara.

At least 37 records · Page 2Linked to original sources

[Symptoms and blood PCB level among chronic Yusho patients, twenty-five years after outbreak].

To investigate the frequency of symptoms and signs and their relationships with blood PCB (polychlorinated biphenyls) levels, twenty-five years after outbreak, we analyzed the data of 276 Yusho patients (male/female: 137/139) who had received health examination in 1993. For this purpose, 31 examination items which correspond or relate to the diagnostic criteria for Yusho (1976) were selected from the examination form. Mean blood PCB concentration in the subjects was 4.69 ppb with the highest value of 31.0 ppb (median : 4.0 ppb). The symptoms for which the proportion exceeded 60% were general fatigue, headache and numbness in extremities. Chronic bronchitis-like symptoms, such as cough and sputum, were observed in 50% of the subjects. Next, the subjects were classified into approximate quartiles of blood PCB: < 3.00, 3.00-4.06, 4.07-5.99, and 6.00+ppb. The distributions of subjects at four levels of blood PCBs were compared between the groups with or without each symptom or sign, using the Cochran-Mantel-Haenszel test. Significant differences were observed for comedones in the trunk (P = 0.02) and other regions (P = 0.02); acneiform eruptions in the genital regions (P = 0.01) and gluteal regions (P = 0.01); and hypersecretion in the Meibomian gland (P = 0.04). Thus, the typical skin and eye symptoms in Yusho patients still persist showing a close relation with blood PCB concentration.

Aged↗

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↗

In vivo 19F NMR comparative study of 5-fluorouracil, 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) and an FT-uracil coadministration system in mouse tumors.

The suppression of alpha-fluoro-beta-alanine (FBAL) formation from 5-fluorouracil (FU) is an important subject in relation to tumor chemotherapy. This is the first comparative study of FU, 1-(2-tetrahydrofuryl)-5-fluorouracil (FT, a prodrug of FU) and of FT+uracil as a coadministration system (UFT) under an oral dose using the in vivo 19F NMR method. The slow release of FU from FT and the suppression of the catabolism of FU to FBAL in mouse livers and tumors by the coadministration of uracil with FT were demonstrated using consecutive NMR measurements. The applicability of the in vivo 19F NMR method to the drug evaluation in tumors and livers of small animals was successfully tested.

Animals↗