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Biomedical subjects

S Yano

Publications and source records attributed to S Yano.

At least 433 records · Page 24Linked to original sources

Ribosome-lamella complexes observed in an Epstein-Barr virus-producing B-cell line, infected with human T-lymphotropic virus type I.

Co-cultivation of peripheral blood mononuclear cells, from a 4-year-old boy with infectious mononucleosis, with a human T lymphotrophic virus type I (HTLV-I)-producing T-cell line resulted in the establishment of an HTLV-I infected Epstein-Barr virus (EBV)-producing B-cell line. Ultrastructural examination revealed the presence of ribosome-lamella complexes (RLCs), in a small proportion of long-term cultured cells. Evidence is presented of continuity between RLC and the rough endoplasmic reticulum, and in some instances there was also an intimate relationship with tubuloreticular structures. The findings support the view that RLC is derived from the rough endoplasmic reticulum and also provide further evidence of the non-specific nature of RLC in relation to cell type.

B-Lymphocytes↗

Serial imaging of Menkes disease.

The patient developed myoclonic seizures at 3 months of age and his hair demonstrated the pili torti pattern. The low serum copper content and ceruloplasmin confirmed the diagnosis of Menkes disease. The characteristic signs on the images were: high echo level regions in the cerebrum as detected by brain ultrasonography, low density areas of white matter detected by CT scan, and low signal intensities of white matter by both T1 and balanced MR images.

Brain↗

Reduction in microalbuminuria in diabetics by eicosapentaenoic acid ethyl ester.

Eicosapentaenoic acid (EPA) ethyl ester (1.8 g/d) was administered to 16 diabetic patients (5 insulin-dependent and 11 noninsulin-dependent diabetics) for 6 mon. EPA in total plasma fatty acids increased from 4.0 +/- 2.4 mol% (mean +/- SD) to 7.5 +/- 3.1 mol% (p less than 0.001). Albumin excretion, measured with spot urine, was significantly reduced from 65 to 36 mg/g creatinine (geometric means, p less than 0.001). Fasting blood sugar levels, glycohemogloblin, body weight and blood pressure did not change significantly during the study. There were also no significant changes in serum levels of creatinine, urea nitrogen, total cholesterol and triglycerides. Although no overt hemorrhage was observed in the patients, hematocrit was reduced from 42.6 +/- 2.8% to 41.0 +/- 3.9% (p less than 0.02). Ten other similar diabetic patients (4 insulin-dependent and 6 noninsulin-dependent diabetics) were followed as a reference group, not concomitantly, for 6 mon with neither EPA ethyl ester nor placebo. The parameters mentioned above were not changed significantly in this group during 6 mon. EPA administration might retard the appearance of overt diabetic nephropathy.

Aged↗

Inhibition of intracellular sorting and processing of lysosomal cathepsins H and L at reduced temperature in primary cultures of rat hepatocytes.

Our recent studies with pulse-chase kinetic analysis in primary cultures of rat hepatocytes suggest that newly synthesized lysosomal cathepsins H and L are initially synthesized as larger proform enzymes, and then the precursor molecules are subsequently converted to the mature enzymes by limited proteolysis during the intracellular sorting process. This proteolytic maturation of procathepsins appears to proceed within an acidic environment, and these processing events are closely connected with the activation of enzymes. To further characterize the intracellular processing site for lysosomal cathepsins H and L, the pulse-chase kinetic study was carried out at 20 degrees C in cultured rat hepatocytes, because the transport of the procathepsins was expected to be blocked at the trans-Golgi compartment at 20 degrees C. We show here that the newly synthesized procathepsins are accumulated intracellularly and the processing for lysosomal cathepsins is completely arrested at 20 degrees C along the sorting pathway. The procathepsins thus accumulated in the cell are presumed to be transported to the Golgi complex, since the oligosaccharide moieties of these polypeptides appear to be phosphorylated. When the cells were shifted to 37 degrees C after an incubation for 4 h at 20 degrees C, a gradual increase of the mature forms was found. However, the processing kinetics generating the mature enzymes were slow compared to those in control cells at 37 degrees C. When the NH4Cl was present in the cells after the temperature shift to 37 degrees C, the intracellular processing of procathepsins was considerably retarded and the release of intracellular procathepsins into the extracellular medium was observed. These results indicate that NH4Cl might exert the inhibitory effect on the mannose 6-phosphate receptor-mediated intracellular targeting mechanism for the lysosomal cathepsins. Hence, the intracellular location of procathepsins accumulated at 20 degrees C is considered to be in proximity to the trans-Golgi compartment. Taken together, the present observations suggest that the propeptide-processing step for procathepsins, which is a critical step for generating the active enzymes, proceeds within the prelysosomal compartment or the lysosomes after the enzymes leave the trans-Golgi compartment.

Ammonium Chloride↗

Effect of FK506 treatment on allocytolytic T lymphocyte induction in vivo: differential effects of FK506 on L3T4+ and Ly2+ T cells.

Although FK506 has been widely investigated as a potent suppressor of organ allograft rejection in animals, little is known about the effect of FK506 on T cell responses to allografts in vivo. In the present study, we have studied the effect of FK506 on the induction of allocytolytic T lymphocyte using mice primed with alloantigens and treated with FK506. FK506 suppressed the CTL induction of spleen cells and peritoneal exudate cells (PEC) in a dose-dependent manner. Time-course kinetic studies indicated that the CTL activity was markedly dependent on the time of administration of FK506 to the mice. Lymphocytes from these FK506-treated animals were found to be reactivated upon exposure to the same alloantigens in a secondary mixed lymphocyte culture (MLC). Furthermore, FK506 was shown to have a differential effect on the activation of helper (L3T4+) and cytotoxic (Ly2+) T cell subpopulations. L3T4+ T cells from the mice primed with alloantigens and treated with FK506 had normal helper activity in the generation of CTL in MLC, whereas Ly2+ T cells from these mice were profoundly suppressed CTL activity upon reexposure to the same alloantigens in a secondary MLC. Exogenous IL-2 or L3T4+ T cells could overcome the immunosuppressive effect of FK506 on the CTL induction of Ly2+ T cells in a secondary MLC. Finally, we have demonstrated that this FK506 effect appeared to be antigen nonspecific since Ly2+ T cells from alloprimed FK506-treated mice failed to induce CTL against the third-party alloantigens as well as the same alloantigens in a secondary MLC.

Animals↗

FK506, a novel immunosuppressive agent, induces antigen-specific immunotolerance in active Heymann's nephritis and in the autologous phase of Masugi nephritis.

FK506 is a new drug which has potent immunosuppressive activity. We studied its immunosuppressive effects on active Heymann's nephritis and the autologous phase of Masugi nephritis. The induction of active Heymann's nephritis was completely suppressed by FK506 injected simultaneously with the antigen (day 1) and then daily for 14 days at a dose of 0.64 mg/kg per day or more. With a lower dosage of this agent, antibody production and immune deposits in the glomerular basement membrane occurred despite the suppression of proteinuria. Similar results were obtained in rats on other treatment schedules (1-7 days or day 8-14 days duration). Rats that were prevented from developing Heymann's nephritis or the autologous phase of nephrotoxic antiserum nephritis by FK506 treatment exhibited a suppressed immune response to a second immunization of the same antigen even 4 weeks after cessation of drug administration: however, they developed antibodies when inoculated with other antigens. Rat peripheral leucocyte counts and serum creatinin were not remarkably influenced by the administration of FK506. These results indicate that FK506 has potent immunosuppressive activity, and it is suggested that it is able to induce an antigen-specific immunotolerance.

Animals↗

Cerebral and abdominal arterial hemodynamics in preterm infants with patent ductus arteriosus.

Using Doppler echocardiography we evaluated the effect of ductal shunt flow on the cerebral and abdominal arterial blood flow in 25 preterm infants. Eligible for inclusion in this study were healthy preterm newborn infants. They were divided into two groups based on their gestational age: group A, 33-36 weeks (15 infants) and group B, 28-32 weeks (10 infants). Two-dimensional Doppler echocardiograms were obtained in each infant during the first 8 hours of life and repeated every 6-12 hours until no ductal shunt flow could be detected. Flow in the ductus arteriosus, the basilar artery and the coeliac artery were examined. Closure of the ductus arteriosus occurred significantly later (p less than 0.05) in group B than in group A. Pulsatility indices of flow in the basilar and coeliac arteries were high when the ductus was patent, decreasing to a fixed level with closure. This study suggests that a shunt of the patent ductus arteriosus (PDA) adversely influences the cerebral and abdominal blood flow in preterm infants.

Abdomen↗

[Studies on the sub-MIC of beta-lactam antibiotics--bactericidal activity in compromised host's serum].

Bactericidal activity in compromised host's serum i.e. patients with cancer, the elderly, diabetes, was stronger than that in normal serum against Proteus mirabilis (P. mirabilis) but was weaker against Klebsiella pneumoniae (K. pneumoniae). Against Escherichia coli (E. coli), bactericidal activity on serum of patients with cancer was weaker in the following order, that in elderly serum, that in diabetic serum. Against Proteus vulgaris (P. vulgaris), bactericidal activity in elderly serum was similar to that in normal serum but was stronger than that in serum of patients with cancer. Against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus), bactericidal activity in elderly serum and diabetic serum was similar to that in normal serum but was weaker than that in serum of patients with cancer. Piperacillin showed bactericidal activity in nutrient broth, normal serum and compromised host's serum at a concentration of 1/4 MIC against E. coli, P. mirabilis and P. aeruginosa. Aspoxicillin showed bactericidal activity in nutrient broth, and bactericidal or bacteriostatic activity in normal serum and serum of patients with cancer against E. coli and P. aeruginosa. While cefazolin and cefmetazole slightly inhibited the growth of bacteria in nutrient broth, they showed hardly any bactericidal activity in normal serum and compromised host's serum.

Aged↗

Stimulatory effect of some therapeutic drugs used for improving cerebral insufficiency on gastric acid secretion in rats.

Baclofen, gamma-amino-beta-hydroxybutyric acid (GABOB), calcium hopantenate (HOPA) and citicoline, which are clinically used for improving cerebral insufficiency, were tested for their effects on gastric acid secretion in the perfused stomach of urethane-anesthetized rats. These drugs were administered intravenously or subcutaneously. They produced a significant increase in gastric acid secretion, although the extents in increase were different. The duration of action was 1-2 h. The potency order was baclofen greater than GABOB greater than or equal to citicoline greater than or equal to HOPA. The stimulatory response to each drug was completely inhibited by atropine. In contrast, the peripheral secretory activity of each drug was not demonstrated in the isolated lumen-perfused stomach of mice. These results indicate that all the tested drugs produce an increase in gastric acid secretion probably via central cholinergic activation and that gastric acid stimulation by compounds improving the cerebral insufficiency might be included in side effects in their clinical use.

Animals↗

Clinical significance of the number of positive tumor markers in assisting the diagnosis of lung cancer with multiple tumor marker assay.

The clinical significance of multiple tumor marker assay in assisting the diagnosis of lung cancer was assessed in 67 patients with primary lung cancer, and 115 with nonmalignant pulmonary disease. The tumor markers studied were carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), squamous cell carcinoma-related antigen (SCC), and tissue polypeptide antigen (TPA). The positive rates for all of the tumor markers were significantly higher in the lung cancer group than in the nonmalignant pulmonary disease group. The sensitivity was 31-66%, the specificity was more than 90% for all five markers, and the accuracy was 69-82%. Among the markers, the positive rate of CEA was best correlated with adenocarcinoma (Ad), NSE with small cell carcinoma (Sm), SCC with squamous cell carcinoma (Sq), CA19-9 with Ad, and TPA with Ad. In multiple tumor marker assay, as the number of combined markers was increased, the sensitivity of the assay became higher and the specificity became lower, resulting in a lower accuracy. However, when more than two markers were positive, the relative possibility of lung cancer was increased 90-100%. The number of positive tumor markers in multiple tumor marker assay indicated that it would be of auxiliary value for the diagnosis of lung cancer.

Antigens, Neoplasm↗

Effects of nifedipine on renal cortical and medullary blood flow in two-kidney, one-clip renovascular hypertension in rabbits.

The effects of nifedipine, a calcium antagonist, on blood pressure and renal regional blood flow were investigated in two-kidney, one-clip renovascular hypertensive rabbits. At 1 week after left renal artery constriction, in the constricted group, systemic blood pressure (BP) significantly rose with the elevation of plasma renin activity (PRA). In both kidneys, renal vascular resistance (RVR on the constricted group was significantly increased as compared to that in the control group. In the clipped kidney, total renal blood flow (RBF) and renal cortical blood flow (RCBF) of the constricted group were significantly decreased, while renal medullary blood flow (RMBF) remained at the control value. In the nonclipped kidney, RBF and RCBF of the constricted group did not significantly change, and RMBF was significantly increased as compared to that of the control group. After administration of nifedipine for 1 week (1.0 mg/kg/day), BP in the constricted group was decreased to the control level and PRA in both groups was increased. The percent change of BP in the constricted group was significantly decreased and the percent change of PRA in the constricted group was significantly increased as compared to those in the control group. Nifedipine increased RBF, RCBF and RMBF and decreased RVR of both kidneys in each group. In the nonclipped kidney, the percent change of RBF, RCBF and RMBF of the constricted group was significantly increased and the percent change of RVR was significantly decreased as compared to those of the control group. In the clipped kidney, only the percent change of RBF of the constricted group was significantly lower than that in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Change in formation of gastric lesions by aspirin during aging in rats.

Formation of gastric lesions induced by orally administered aspirin (100 mg/kg) was examined in 4 to 86 week-old Sprague-Dawley male rats. Gastric mucosal prostaglandin I2 level and gastric secretion in basal state were also examined in these rats. Gastric mucosal PGI2 level was measured by bioassay and gastric secretion was collected by the pyloric ligation method for 4 h. Gastric lesions reached the maximum value in 7 week-old, and lowest in 60 week-old. Acid output also reached the maximum value in 7 week-old. As for PGI2 level, it showed the maximum value in 20 week-old, and moderately decreased thereafter. In 86 week-old, PGI2 level was further lowered to about 35% of 20 week-old rats. A linear positive correlation was noted between formation of aspirin-induced gastric lesion and acid secretion. From these results, it was concluded that formation of gastric lesions by aspirin was closely related to acidity of the gastric secretion. It was also suggested that in aged rats, aspirin-induced gastric lesions may at least partly be associated with the reduced PGI2 level.

Aging↗

Structure-activity relationship of yohimbine and its related analogs in blocking alpha-1 and alpha-2 adrenoceptors: a comparative study of cardiovascular activities.

We investigated the selectivities and structure requirements for alpha-1 and alpha-2 adrenoceptor blocking activities of yohimbine (YO) and its 12 related analogs, such as beta-yohimbine (beta-YO), dihydrocorynantheine (DHC) and (-)indoloquinolizidine ((-)IQ). The affinity of YO analogs to alpha-adrenoceptor was assessed by measuring their blockade of pressor responses to epinephrine in pithed rats. Among YO structure groups, the potency order was YO greater than DHC = beta-YO greater than geissoschizine methylether greater than 14 beta-hydroxy YO greater than 14 beta-benzoyloxy YO (inactive). (-)IQ was slightly less potent than YO, but much stronger than (+)IQ. Among (+/-)IQ structure groups, the potency order was (+/-)IQ greater than (+/-)1,12b-trans-1-hydroxy IQ much greater than (+/-)1,12b-cis-1-hydroxy IQ (inactive). (+/-)Borrerine was active, but (+/-)desmethylborrerine was inactive. The alpha-1 blocking activities of the four compounds YO, beta-YO, DHC and (-)IQ, were assessed in experiments of pressor responses to methoxamine in pithed rats and contractile responses to methoxamine in the rat vas deferens. The potency order was (-)IQ greater than YO greater than DHC greater than beta-YO. Furthermore, the alpha-2 blocking activities of the four analogs were assessed in experiments of pressor responses to clonidine and inhibition of electrically driven cardioacceleration by clonidine, in pithed rats. The potency order was YO greater than beta-YO greater than (-)IQ greater than DHC. Based on the potency ratio between alpha-1 and alpha-2 blocking activities, DHC or YO was most selective for alpha-1 or alpha-2 subtype, respectively, among the four YO analogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Studies on the enzyme immunoassay of bio-active constituents contained in oriental medicinal drugs. V. Preparation of bovine serum albumin conjugate and beta-galactosidase labelled antigen for enzyme immunoassay of 3 beta-(monoglucuron-1' beta-yl)-18 beta-glycyrrhetic acid.

In order to prepare an immunogen for enzyme immunoassay of 3 beta-(monoglucuron-1'-beta-yl)-18 beta-glycyrrhetic acid (3MGA), which was isolated from a patient with glycyrrhizin-induced pseudoaldosteronisms, benzyl glycyrrhetate (3) was allowed to react with an acetobromosugar (2) in the presence of silver carbonate to give benzyl 3 beta-(methyl 2',3',4'-triacetyl-glucuron-1' beta-yl)-glycyrrhetate (5) and methyl 3',4'-diacetyl-alpha-1',2'-O-[1-(benzyl glycyrrhet-3 beta-yl)- ethylidene]-D-glucuronate (4). On the other hand, this reaction was carried out in the presence of mercuric cyanide in nitromethane to give compound 5, benzyl 3 beta-acetyl glycyrrhetate (6) and benzyl 11-oxo-A-neooleana-3(5),12-dien-3-oate (7). 4-Aminomethylcyclohexanecarboxylic acid and glycine were introduced as chemical bridges at C-30 of 3 beta-(tert-butylglucuron-1' beta-yl)-glycyrrhetic acid (11) derived from compound 5. The former bridge was used to prepare an immunogenic conjugate with bovine serum albumin, and the latter bridge was used for antigen labelled with beta-galactosidase.

Animals↗

Field emission scanning electron microscopic study on the noninfarcted myocardium after myocardial infarction.

Intracellular membranous ultrastructural changes in the noninfarcted myocardium of the left ventricle were studied by examining experimental myocardial infarction in rats with a field emission scanning electron microscope. The left coronary artery was ligated at its origin for 7 days. The resulting infarcts comprised approximately 40% of the total area of the left ventricles. In a light microscopic study, the transverse diameter of myocytes had increased to 17.1 +/- 2.9 microns in the noninfarcted myocardium, compared to 14.1 +/- 3.1 microns in the myocardium of sham-operated rats (p less than 0.01). For the scanning electron microscopic study, the specimens were processed according to the Osmium-DMSO-Osmium method. Marked morphological changes of intracellular membranous structures were found in the noninfarcted myocardium, especially in the lacelike network of sarcoplasmic reticulum which occasionally formed large flattened cisternae, and in the marked proliferation of surface caveolae. It is speculated that these early ultrastructural changes in the noninfarcted myocardium reflect an adaptation of microorganellae in the failing hearts of the rats.

Animals↗

Vasoconstrictor effect of endothelin in isolated perfused stomach of the rat in comparison with noradrenaline and serotonin.

In the isolated rat stomach perfused with Krebs-Henseleit solution at 36 degrees C, endothelin induced vasoconstriction in a dose-dependent manner. The threshold dose for inducing vasoconstriction was very small, and the pressor response to a bolus injection at 0.1 nmol lasted more than 1 hr. In contrast, the vasoconstrictor effects of noradrenaline and serotonin were transient. The magnitude of the maximal response to endothelin was almost the same as that to noradrenaline, but greater than that to serotonin. The pressor response to serotonin, but not noradrenaline, was greatly augmented after pretreatment with endothelin. These results suggest that endothelin causes a long-lasting vasoconstriction, which would be associated with its ulcerogenic activity, especially in combination with other vasoactive agents under some pathophysiological conditions.

Animals↗

Centrally mediated inhibitory effect of 5-[2-(diethylamino)ethyl]amino-5,11-dihydro[1]benzoxepino[3,4- b]pyridine trihydrochloride (KW-5805) on gastric acid secretion in rats.

KW-5805, 5-[2-(diethylamino)ethyl]amino-5,11-dihydro[1]benzoxepino[3,4- b]pyridine trihydrochloride, is a new tricyclic compound with antiulcer activities. Its effect on stimulated gastric acid secretion was investigated in the perfused stomach of anesthetized rats. KW-5805 at 0.3-10 mg/kg, i.v., dose-dependently inhibited gastric acid secretion stimulated by 2-deoxy-D-glucose (2-DG). On the other hand, the compound at 10-20 mg/kg, i.v., exerted a moderate decrease in gastric acid secretion stimulated by bethanechol; and at 10 mg/kg, i.v., it produced no change in gastric acid secretion evoked peripherally by vagal electrical stimulation. When applied intracerebroventricularly at 1-5 micrograms/rat, this compound dose-relatedly reduced gastric acid secretion stimulated by 2-DG. Three main metabolites (KF-10504, KF-9530 and KF-10847) of KW-5805 at 1 mg/kg, i.v., caused no significant decrease in gastric acid secretion stimulated by 2-DG. Doxepin, a tricyclic compound, definitely depressed the 2-DG stimulated gastric acid secretion at 1 mg/kg, i.v. It is suggested that intravenous administration of KW-5805 inhibits gastric acid secretion stimulated by 2-DG, mainly via centrally mediated mechanisms, and that biotransformation of KW-5805 to the metabolites contributes little to the development of the antisecretory effect.

Animals↗