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Biomedical subjects

N Sakamoto

Publications and source records attributed to N Sakamoto.

At least 361 records · Page 20Linked to original sources

Neurotensin immunoreactive structures in the human infant striatum, septum, amygdala and cerebral cortex.

Neurotensin immunoreactive (NT-IR) neuronal perikarya are present in small numbers in the bed nucleus of the stria terminalis, lateral olfactory stria, substantia innominata, caudate nucleus and putamen of the human infant forebrain. Larger numbers of perikarya are present in the amygdala and related structures. NT-IR axons are present in the medial septal area, bed nucleus of the stria terminalis, caudate nucleus, putamen and amygdala. The cerebral cortex contains a rich network of NT axons with an accentuation in layer II. This network appears to be derived from bundles of axons which traverse the deep white matter from the thalamus.

Amygdala↗

Neurotensin immunoreactivity in the human cingulate gyrus, hippocampal subiculum and mammillary bodies. Its potential role in memory processing.

Neurotensin immunoreactive neurons comprise the majority of large perikarya in the human subiculum and project axons to the alveus, fimbria, fornix and neuropil of the mammillary bodies. These regions are prominently involved in conditions such as Wernicke's and Alzheimer's disease in which memory is impaired. Neurotensin has potential significance as a peptide in a human brain circuit which may serve a role in memory processing.

Female↗

A neurotensin-immunoreactive pathway from the subiculum to the mammillary body in the rat.

The existence of a neurotensin-like immunoreactive (NT-IR) pathway from the subiculum to the mammillary body was demonstrated in very young rats using immunocytochemistry, knife cut, electric lesion and retrograde tracer techniques. Unilateral hemitransection of the dorsal fornix caused a marked reduction of NT-IR fibers in the ipsilateral mammillary body. Unilateral electric lesion of the subiculum also resulted in ipsilateral reduction of NT-IR fibers in the mammillary body. Biotin-wheat germ agglutinin (B-WGA), injected into the mammillary body, labeled neurons in the ipsilateral subiculum which were shown by double staining to have NT-IR cytoplasm. These findings demonstrate the presence of a major NT-IR fiber pathway from the subiculum to the mammillary body via the fornix.

Animals↗

A copper-sulfur complex in the liver of a patient with Wilson's disease.

An asymptomatic 16-year-old boy was found to have Wilson's disease without Kayser-Fleischer rings. Liver biopsy showed chronic active hepatitis with 1025 micrograms copper/g dry weight. After 19 months of d-penicillamine therapy, the liver histology became almost normal and the copper content decreased to 238 micrograms/g dry weight. The liver specimens obtained before and after treatment were studied by X-ray probe microanalysis. After treatment, both copper and sulfur decreased in hepatocellular lysosomes. The estimated molar ratio of the decreased copper to the decreased sulfur was 32/100. These figures suggest that lysosomal copper exists in the form of metallothionein.

Adolescent↗

In vitro synthesis of antibody to hepatitis B virus antigen by circulating lymphocytes from chronic HBsAg carriers and patients with acute hepatitis B.

It is not clear what determines the outcome of hepatitis B surface antigen (HBsAg) infection, although evidence suggests that the absence of antibody to HBsAg (anti-HBs) is responsible for the development of the carrier state. The synthesis of immunoglobulin G (IgG), anti-HBs and antibody to hepatitis B core antigen (anti-HBc) was measured in pokeweed mitogen-stimulated cultures of peripheral blood mononuclear cells from 12 chronic HBsAg carriers, 5 patients with acute hepatitis B (AHB) during recovery phase and 11 subjects with anti-HBs in serum (controls). All 3 groups showed similar amounts of IgG synthesis. Anti-HBc was detectable in lymphocyte cultures of 10 of 12 chronic HBsAg carriers and 2 of 5 AHB patients, but in none of the controls. Anti-HBs was found in cultures from 6 of 11 controls, and not in carriers or AHB patients. Both in vitro anti-HBc and anti-HBs levels correlated significantly with serum titers of anti-HBc and anti-HBs respectively. B cells from controls cocultured with irradiated (helper) T cells from carriers and AHB patients produced anti-HBs normally. In contrast, B cells from 11 of 12 carriers and 3 of 5 AHB patients cocultured with irradiated control T cells did not synthesize detectable amounts of anti-HBs although they synthesized normal amounts of IgG and anti-HBc. T cells from 8 of 12 carriers and all AHB patients suppressed anti-HBs synthesis by mixtures of control B cells and control irradiated T cells, but these T cells did not affect IgG synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Specificity↗

Validity of transfer-function representation of input-output relation in allosteric models.

A transfer-function representation of reaction velocity is devised to describe analytically and approximately an input-output response of allosteric enzyme around a steady state. The transfer function is derived on assuming an exponential change in reaction velocity for the indicial response to substrate influx rate. The validity of the representation with variation in the kinetic parameters and flow rates is examined for the response of Koshland-Nemethy-Filmer (KNF) and Monod-Wyman-Changeux (MWC) dimeric models by comparing with the exact response obtained from the computer simulation, that is, by numerical integration of the rate equation. The representation has a wider valid region with a decrease in influx rate than with an increase. For the KNF model the representation is valid for negative cooperativity, but invalid for positive cooperativity. For the MWC model the validity decreases with stronger cooperativity. With the transfer functions valid for the Michaelis-Menten and allosteric reactions, we may derive the transfer-function representation for many metabolic pathways.

Allosteric Regulation↗

Inhibitory effects of anti-angiogenic agents on neovascularization and growth of the chorioallantoic membrane (CAM). The possibility of a new CAM assay for angiogenesis inhibition.

Protamine sulfate and combinations of heparin-cortisone acetate known as having anti-angiogenic activities impaired the growth of chorioallantois at the dose inducing no decrease in growth rate of the embryos. This inhibitory effect of the agents is presumed to be mediated by the specific inhibition of the growth of endothelial cells forming chorioallantoic blood vessels based on the following results: significant correlations were found between the length of CAM vessels measured by an automatic image analyzer and the estimated volumes of chorioallantois (correlation coefficient r = 0.94) and these agents specifically inhibited the (3H)-thymidine incorporation into cultured endothelial cells at the dose having no effects on that into cultured chick embryonic cells. On the other hand, all DNA-synthesis inhibitors, mitomycin C, 5-fluorouracil, and paraformaldehyde suppressed the growth of both CAM and embryo and resulted in early embryonic death, which might be due to the nonspecific impairment of DNA synthesis by these agents. These results indicate the possibility that the present CAM assay could screen agents having anti-angiogenic activity.

Allantois↗

Improved insulin sensitivity in carbohydrate and lipid metabolism after physical training.

To estimate physical training effects quantitatively, the relationship between tissue sensitivity to exogenous insulin (glucose metabolism determined by euglycemic insulin-clamp technique) and maximal oxygen uptake (VO2 max) was defined in 9 well-trained athletes and 14 untrained subjects with normal glucose tolerance. Tissue sensitivity to exogenous insulin in the athletes was significantly higher than in the controls (P less than 0.001). Seven untrained subjects continued the physical exercise program. After physical training for 1 month, glucose metabolism increased from 40.3 +/- 3.9 mumol/kg/min to 42.2 +/- 4.4 mumol/kg/min (P less than 0.05) and VO2 max also increased significantly (P less than 0.05). During euglycemic hyperinsulinemia, both plasma FFA (P less than 0.001) and glycerol (P less than 0.05) decreased rapidly after physical training. Glucose metabolism directly correlated with VO2 max (P less than 0.001). These results suggest that the euglycemic insulin-clamp technique provides a reliable estimate of training effects, tissue sensitivity to physiologic hyperinsulinemia is 46% higher in trained athletes, and physical training improves insulin sensitivity not only in glucose metabolism but also in lipid metabolism.

Adolescent↗

Enhancement of antibody production to hepatitis B surface antigen by anti-idiotypic antibody.

Studies were undertaken to determine whether anti-idiotypic antibody (anti-Id) against antibody to hepatitis B surface antigen (anti-HBs) could modulate in vitro anti-HBs production by human peripheral blood mononuclear cells stimulated with pokeweed mitogen. Peripheral blood mononuclear cells from patients positive for serum anti-HBs produced significantly increased amounts of anti-HBs by the addition of IgG fraction of anti-anti-HBs as well as purified HBsAg in a soluble form when compared to those in cultures with pokeweed mitogen alone. F(ab')2 but not Fc fragments of anti-anti-HBs significantly enhanced anti-HBs levels in cultures. Anti-anti-HBs or HBsAg alone, however, did not induce anti-HBs production. Anti-HBs production was not observed by the additions of these additives when peripheral blood mononuclear cells from chronic HBsAg carriers and control individuals were used. These findings indicate that anti-Id modulates the immune response to HBsAg.

Antibodies, Anti-Idiotypic↗

Mechanism of central hyperglycemic effect of cholinergic agonists in fasted rats.

The influence of cholinergic agonists on central nervous system (CNS) regulation of blood sugar homeostasis was studied in fasted rats. When carbachol, muscarine, bethanechol, methacholine, or neostigmine was injected into the third cerebral ventricle, it caused a dose-dependent increase in the hepatic venous plasma glucose concentration. However, in the case of 1,1-dimethylphenyl-4-piperazinium iodide (DMPP) or nicotine, the level of hepatic venous glucose did not differ from that of the saline-treated control rats. The increase in glucose level caused by neostigmine was dose-dependently suppressed by coadministration of atropine. These facts suggest that cholinergic activation of muscarinic receptors in the CNS plays a role in increasing hepatic glucose output. Injection of neostigmine (5 X 10(-8) mol), an inhibitor of cholinesterase, into the ventricle resulted in the increase of not only glucose, but also glucagon, epinephrine, and norepinephrine in the hepatic venous plasma. However, constant infusion of somatostatin through a femoral vein completely prevented the increase of glucagon after administration of neostigmine, although the increase of hepatic venous glucose and epinephrine levels were still observed. Neostigmine-induced increments in glucose did not occur in adrenalectomized rats. This suggests that the secreted epinephrine acts directly on the liver to increase hepatic glucose output.

Adrenalectomy↗

Increase in plasma glucose concentration after intracerebroventricular injection of N,O'-dibutyryl cyclic adenosine 3',5'-monophosphate.

The effect of chemical stimulation of the central nervous system was studied in anesthetized rats. (Bu)2 cAMP, cAMP, 5'-adenosine monophosphate (AMP), ATP, and (Bu)2 N6,O2-dibutyryl guanosine-3'5'-cyclic monophosphate sodium salt were injected directly into the third cerebral ventricle, and changes in hepatic venous plasma glucose, immunoreactive glucagon, and insulin concentrations were studied. The injection of (Bu)2cAMP (1 X 10(-8) to 5 X 10(-7) mol/microliter saline) into the third cerebral ventricle caused a dose-dependent hyperglycemia associated with increased immunoreactive glucagon. (Bu)2cAMP-induced hyperglycemia and hyperglucagonemia were inhibited by prior bilateral adrenalectomy. The injection of somatostatin (1 X 10(-9) mol) with (Bu)2cAMP (5 X 10(-7) mol) into the third cerebral ventricle abolished both (Bu)2cAMP-induced hyperglycemia and an increase of glucagon secretion. These results suggest that cAMP may act intracellularly within the central nervous system to increase hepatic glucose output, and this appears to depend on the adrenal gland. Epinephrine secreted from the adrenal gland may directly act on the liver or enhance glucagon secretion, which in turn increases hepatic glucose output.

Adenosine Triphosphate↗

[Bacterial and clinical studies on imipenem/cilastatin sodium in urological infection].

Antibacterial activities of imipenem (MK-0787), cefazolin (CEZ), cefmenoxime (CMX) and cefoperazone (CPZ) were measured by using an agar dilution method against 243 strains of bacteria isolated from the patients with urinary tract infections. The MIC80 of MK-0787 against S. epidermidis, E. faecalis, E. coli, K. pneumoniae, E. cloacae, S. marcescens, P. mirabilis, P. vulgaris and P. aeruginosa was less than or equal to 0.10, 3.13, less than or equal to 0.10, 0.20, 0.78, 1.56, 3.13, 3.13 and 6.25 micrograms/ml, respectively. MK-0787 was more active than CEZ, CMX and CPZ against all bacterial species except Proteus spp. Imipenem/cilastatin sodium (MK-0787/MK-0791) 500 mg/500 mg two times a day for 5 days was given to 31 cases of chronic complicated urinary tract infections and a case of acute prostatitis. Overall clinical effectiveness rate judged by the criteria proposed by the Japanese UTI committee in 22 cases of chronic complicated urinary tract infection treated with MK-0787/MK-0791 was evaluated to be 86% including excellent in 6 cases, moderate in 13 cases and poor in 3 cases. As side effects, 2 cases encountered eruption or anorexia. Abnormal laboratory findings were observed in 6 cases.

Adult↗

Hypoglycemic activity of MTP-1403 (2-amino-7,8-dihydro-4-piperazinyl-6H-thiopyrano 3,2-d pyrimidine), a new hypoglycemic agent.

2-Amino-7,8-dihydro-4-piperazinyl-6H-thiopyrano 3,2-d pyrimidine (MTP-1403) is a new oral hypoglycemic agent structurally different from any existing hypoglycemic drugs. MTP-1403 lowered fasting plasma level and dose-dependently improved glucose tolerance test without increasing insulin secretory response to glucose. MTP-1403 caused a decrease in fasting plasma glucose level in mild alloxan-induced diabetic rats but not in the rats suffering from ketosis. MTP-1403 markedly improved the oral glucose tolerance test in the genetically diabetic KK mice. These results suggest that hypoglycemic activity of MTP-1403 may be mechanically different from sulfonylureas and biguanides and beneficial to type II diabetics with hyperinsulinemia and insulin resistance.

Animals↗

Nasal resistance measured by anterior rhinomanometry.

The technique and principle of the active anterior rhinomanometry were justified by human examination and model experiment. The resistance values obtained from anterior method did not always agree with those from posterior one. Causes of the disagreement were considered to be distortion of the nostrils, air leakage from the apparatus and resistive component in the nasopharynx. These possibilities were demonstrated and analyzed in model experiments. The anterior rhinomanometry was concluded as a precise and convenient method to assess the conductivity of the nasal cavities.

Airway Resistance↗

[Effects of indeloxazine hydrochloride on brain energy and glucose metabolism in the four-vessel occlusion rat model].

Indeloxazine hydrochloride (Indeloxazine) has been known as a new type drug with enhancing effects on memory and learning processes in various experimental models. In the present studies, effects of Indeloxazine on brain energy and glucose metabolisms were determined in four-vessel occlusion rat model. Since a critical point of ischemic time for the recovery of brain energy levels existed between 30 min and 60 min in this model, effects of Indeloxazine were determined in the rat model of 60 min recirculation following 60 min ischemia. One-week dosing of Indeloxazine at 2 mg/kg showed slight increases in ATP and total adenine nucleotides levels. To elucidate the mechanism of improving action of Indeloxazine on brain energy levels, effects on glucose metabolism were determined. Non-treated group of 60 min ischemia-60 min recirculation showed severe reduction of 14C-2-deoxyglucose metabolism in comparison to normal control group. Indeloxazine-treated group showed a slight improvement of 14C-2-deoxyglucose metabolism in comparison to non-treated group. Furthermore, high 14C-2-deoxyglucose metabolism was observed in parts of hippocampus, cortex and thalamus. From these results, it seems possible that Indeloxazine has some protective effects on brain damage in four-vessel occlusion rat model.

Animals↗