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M Nishimura

Publications and source records attributed to M Nishimura.

At least 1,567 records · Page 87Linked to original sources

HPLC/circular dichroism detection using a split-type flow cell for polarized photometric detector.

HPLC/circular dichroism detection using a conventional spectrophotometric detector has been established. A split-type flow cell developed for a polarized photometric detector, which is a non-modulated polarimeter, was inserted into this detector. When two rays of circularly polarized light with opposite rotational senses to each other were incident in both cells by combining a polarizer and a 1/4 wave retarder in front of the cell assembly, the output from this spectrophotometric detector became solely the signal based on circular dichroism. Selective detection of a chiral analyte, in which the ratio of the difference in the absorbance between two rays mentioned above and the absorbance by normal rays in over 1/1000, is feasible using the proposed instrument.

Chromatography, High Pressure Liquid↗

Theoretical consideration on polarized photometric detection.

Previously, we developed a novel detector, a polarized photometric detector for optically active compounds, where two polarizers are set on either side of the UV-visible absorbance detector flow cell. In this paper, we present theoretical considerations on this method with several equations. If the inclined angle of the second polarizer is defined as alpha (left when alpha > 0 degree), the following equation is obtained: delta Abs = 2 log e.tan alpha.beta, where delta Abs is the change in absorbance and beta (magnitude of beta << alpha) is the angle of rotation of light passing through the cell containing the optically active compound. This equation suggests that delta Abs is proportional to the analyte concentration and that the dextro- and laevorotatory compounds are detected as positive and negative absorbance changes, respectively. The theoretical maximum signal to noise (S/N) ratio is obtained when alpha = 45 degrees (= 0.8 rad) and the smallest detection limit is 5 x 10(-5) degrees (S/N = 3) when the path length of the flow cell is 10 mm. This detector was successfully used in flow injection analysis (FIA) as well as HPLC for optically active compounds.

Chromatography, High Pressure Liquid↗

Surgical approach to early gastric cancer with lymph node metastasis.

The clinicopathology of our series of patients (n = 486) with early gastric cancer was reviewed with special reference to metastasis to the regional lymph nodes. The incidence of lymph node metastasis was 15.8% (19/120) in patients with the protruded type of carcinoma and 11.7% (42/360) in patients with the depressed type of carcinoma. It was especially high in carcinomas of the IIa + IIc type of the former group. The incidence of lymph node involvement was higher in the group with larger tumors (greater than 30 mm) than in the group with smaller tumors (less than or equal to 30 mm). Metastatic lesions were detected in as many as 25.0% (16/64) of the cases with large tumors (greater than or equal to 50 mm); however, of the 46 cases with small tumors (less than 10 mm), 1 case had metastases to the nodes of group 1. There were 4 cases of m-cancer with metastasis to group 1 lymph nodes. Skip metastasis to group 2 lymph nodes was discovered in 4 cases. From these results, we feel that the standard operation for early gastric cancer is R2-gastrectomy including the complete removal of group 1 and 2 lymph nodes. R1-gastrectomy or local resection is thought to be sufficient for m-cancer with a lesion smaller than 10 mm in maximum diameter.

Adenocarcinoma↗

Biotransformation of BOF-4272, a sulfoxide-containing drug, in the cynomolgus monkey.

BOF-4272, (+/-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one), is a new drug intended for the treatment of hyperuricemia. This report describes the pharmacokinetics and detailed metabolic pathways of BOF-4272 in the cynomolgus monkey, which were investigated using the metabolites found in plasma, urine, and faeces after intravenous and oral administration. M-4 was the main metabolite in plasma after intravenous administration. M-3 and M-4 were the main metabolites in plasma after oral administration. The Cmax and AUC(0-t) of M-4 were the highest of all the metabolites after intravenous administration. The Cmax and AUC(0-t) of M-3 were the highest of all the metabolites, and those of M-4 were the second highest, after oral administration. M-4 and M-3 were the main metabolites detected in urine and faeces, respectively, after intravenous administration, with M-4 and M-3 at 47.2% in urine and 19.1% in faeces, respectively, within 120 h after administration. M-4 was the only metabolite detected in urine after oral administration, at about 5% within 120 h after administration. M-3 was detected in faeces at 17.0% within 120 h after oral administration. These results suggest that, in the cynomolgus monkey, BOF-4272 is rapidly biotransformed to a main metabolite (M-4, a sulphoxide-containing metabolite of BOF-4272) and that M-4 is mainly excreted in urine and possibly also in bile, with subsequent conversion to M-3 by the intestinal flora. It is expected that the biotransformation of BOF-4272 would be similar in healthy human volunteers.

Animals↗

Central and peripheral nervous system pathology of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency.

An autopsy case of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency is presented. A 15-year-old boy had mental retardation, epilepsy, and peripheral neuropathy. A sural nerve biopsy revealed a decreased number of myelinated fibers, abnormally thick myelinated fiber groups, and numerous thinner unmyelinated fibers. The autopsy study revealed unusual findings of peripheral neuropathy and spheroid formation in addition to arterial structural abnormalities and perivascular demyelination which are common in cases of homocystinuria. The peripheral neuropathy and spheroid formation may be related to the low level of serum folic acid. The presence of peripheral neuropathy should be ascertained in cases of 5,10-methylenetetrahydrofolate reductase deficiency.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗

Effect of preanesthetic rectal famotidine on pH and volume of gastric contents in pediatric outpatients.

STUDY OBJECTIVE: To determine the feasibility and effects of preanesthetic rectal famotidine on gastric fluid pH and volume in pediatric patients. DESIGN: Randomized, prospective, double-blind, controlled study. SETTING: Operating room at a medical center. PATIENTS: Eighty patients undergoing minor surgery under general anesthesia randomly allocated to one of two groups. INTERVENTIONS: Thirty-four patients in Group 1 were given 0.5 mg/kg of diazepam rectally 30 to 120 minutes before anesthesia induction. Thirty-eight patients in Group 2 received 1 mg/kg of famotidine, a new histamine (H2) blocker, and 0.5 mg/kg of diazepam through the same route. Six patients in Group 1 and two patients in Group 2 were excluded from the study due to gastrointestinal (GI) disorders. MEASUREMENTS AND MAIN RESULTS: Patients with gastric pH less than 2.5 or volume of gastric contents greater than 0.4 ml/kg were considered to be at risk for pulmonary aspiration. Thirty-five (92%) of the Group 2 patients had gastric contents with pH greater than 2.5 and gastric volume less than or equal to 0.4 ml/kg. Only 13 (38%) of the patients in Group 1 had similar gastric pH and volume. Rectal administration did not cause the children pain, and no anorectal problems of famotidine were detected. CONCLUSIONS: Famotidine 1.0 mg/kg administered rectally 30 minutes prior to general anesthesia appears to result in a satisfactory increase in gastric pH.

Administration, Rectal↗

Endothelium-dependent relaxation in peripheral vasculature and kidney of non-insulin-dependent diabetes mellitus.

Desmopressin (DDAVP), an AVP.V2-receptor agonist, evokes endothelium-dependent relaxation (EDR) due to nitric oxide (NO), EDR factor (EDRF) in the systemic vasculature, and glomerular afferent arterioles via AVP receptor(s). Glyceryl trinitrate (GTN) causes endothelium-independent (nonreceptor-mediated) vasodilation. We elucidated the possible involvement of EDRF in early non-insulin-dependent diabetes mellitus (NIDDM) and glomerular hyperfiltration (GHF) by DDAVP and GTN infusions. Patients with advanced DM nephropathy (DM.Np) (n = 7) were also examined. DDAVP and GTN decreased the mean blood pressure in DM with GHF (DM + GHF) and without GHF (DM-GHF) greater than that in normal subjects (N), without any difference in the heart rate changes in any group. Plasma levels of cGMP, a cellular messenger of NO, were significantly increased by DDAVP and GTN with a similar increment in each group. DDAVP caused a significant increase in urinary cGMP excretion in each group with a similar increment in each group. However, it caused a transient increase in creatinine clearance only in DM + GHF although GTN did not, and an exaggerated excretion of urinary albumin in early NIDDM, especially in DM+GHF, without a change in beta 2-microglobulin excretion. In contrast, in DM.Np GTN caused a decrease in blood pressure and an increase in plasma cGMP levels, but DDAVP did not. In conclusion, in peripheral vasculature and kidney, an enhanced sensitivity of vascular smooth muscle to NO is present in early NIDDM. The exaggerated dilation of glomerular afferent arterioles by preferentially produced NO in in situ, which causes a rise in PGC, might be partly responsible for the glomerular hyperfiltration and subsequently the increase in the glomerular protein permeation of DM+GHF. However, in peripheral blood vessels of DM.Np EDR is impaired. Thus, EDR seems to change with the development of NIDDM.

Adult↗

Effect of AVP.V1-receptor antagonist on urinary albumin excretion and renal hemodynamics in NIDDM nephropathy: role of AVP.V1-receptor.

We examined the effect of an orally effective, nonpeptide AVP.V1-receptor antagonist, OPC21268, on urinary albumin excretion and renal hemodynamics in non-insulin dependent diabetes mellitus (NIDDM) patients (seven patients with microalbuminuria, four with overt nephropathy, and three with normoalbuminuria) and in three normal subjects. The oral administration of 100 mg of OPC21268, which is sufficient to suppress the vasoconstriction induced by exogenously infused AVP, caused a significant decrease in urinary albumin excretion only in NIDDM with microalbuminuria concomitantly with a slight decrease in filtration fraction and glomerular filtration rate (GFR). On the other hand, urinary beta 2 microglobulin excretion did not change at all during the study. Neither change in systemic blood pressure, in heart rate, nor in plasma vasoactive substance levels (ANP, renin activity, aldosterone, and AVP) was observed in all four groups. In conclusion, in NIDDM patients with microalbuminuria, an increase in the sensitivity of contraction of glomerular efferent arterioles via an activation of AVP.V1-receptor(s) is at least present, and AVP.V1-receptor antagonist causes a decrease in urinary albumin excretion due partly to decrease the intraglomerular capillary pressure. This compound may be useful for the treatment of NIDDM microalbuminuria.

Administration, Oral↗

The effect of PGI2 analogue on vascular endothelial function and platelet aggregation in patients with NIDDM.

The effect of the short-term administration of beraprost sodium, an analogue of prostaglandin I2 (PGI2), on the function of vascular endothelial cells and platelet in non-insulin-dependent diabetes mellitus (NIDDM) patients was investigated. Seven nonobese NIDDM patients with microalbuminuria were recruited for this study. They received a dose of 20 micrograms of beraprost sodium three times daily for 1 month. Before and after this treatment, various factors concerning functions of vascular endothelial cells and platelet were measured. Treatment with PGI2 analogue caused a decrease in basal levels of plasma lipoprotein (a) from 16.8 +/- 5.3 to 13.2 +/- 4.4 mg/dL (p < 0.05), immunoreactive-(i)endothelin from 2.4 +/- 0.3 to 1.6 +/- 0.2 pg/mL, and i-thrombomudulin from 9.3 +/- 3.7 to 7.9 +/- 3.0 FU/L, respectively, and caused a significant increase in basal plasma i-tissue type plasminogen activator (tPA) from 5.3 +/- 0.7 to 8.3 +/- 1.5 ng/mL (p < 0.01). This treatment also increased maximum response of i-tPA induced by desmopressin infusion. Platelet aggregation due to ADP was inhibited in five of six patients after this treatment. In conclusion, treatment with PGI2 analogue caused a decrease in the presumed promoting factors of angiopathy such as lipoprotein (a) and endothelin and an increase in the protecting endothelial factor of angiopathy, tissue type plasminogen activator in patients with NIDDM. And immunoreactive thrombomodulin levels which reflect the vascular endothelial cell injury tended to decrease with the treatment. Therefore, it is suggested that this treatment preserves the vascular endothelial function in diabetes.

Adult↗

Normal brain development in PS1 hypomorphic mice with markedly reduced gamma-secretase cleavage of betaAPP.

Presenilin 1-null mice die at birth from brain and skeletal developmental deformities due to disrupted Notch signaling. Presenilin 1-null mice also have severely reduced gamma-secretase cleavage of betaAPP. The assumption has been that facilitation of Notch signaling and betaAPP processing by presenilin 1 are analogous functions. Here we describe a presenilin 1-targetted mouse model that expresses extremely low levels ( approximately 1% of normal) of mutant PS1-M146L. Homozygous mice have significantly reduced viability due to a Notch-like phenotype. The animals that survive have severe axial skeletal deformities and markedly diminished gamma-secretase activity and accumulation of betaAPP-C100, but no obvious abnormalities in brain development. These results suggest that, in mice, a marked reduction of PS1-facilitated gamma-secretase activity is not detrimental to normal brain development.

Amyloid Precursor Protein Secretases↗

Immunocytochemical studies on a fetal brain of tuberous sclerosis.

A female stillborn baby was delivered at 36 weeks' gestation. There were rhabdomyomas in the heart, multi-cystic kidneys, and tubers in the brain. Neuropathologic examination of the brain tissue revealed typical giant cells in the sub-ependymal nodules, cerebral white matter, and cortex. On immunocytochemical staining, the giant cells stained positively with antisera to glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and neuron-specific enolase (NSE). The giant cells as well as adjacent glial cells with small eccentric nuclei contained both MBP and GFAP. Both cell types combined immunocytochemical characteristics of astrocytes and oligodendrocytes. There were also intermediate-sized cells found among giant cells and germ cells in subependymal nodules. In white matter nodules, similar intermediate-sized cells were found among giant cells and glial cells with small eccentric nuclei. Therefore, giant cells as well as glial cells with small eccentric nuclei may be multi-potential and may result from abnormal patterns of maturation.

Brain↗

Beneficial effects of fish oil on glucose metabolism in spontaneously hypertensive rats.

1. Increased interest in fish oil led us to examine their metabolic effects in spontaneously hypertensive rats, which have been reported to have glucose intolerance. 2. Rats were divided into three groups: (i) a control group fed standard rat laboratory chow; (ii) a lard group fed a high-fat diet containing 20% lard; and (iii) a fish oil group fed a high-fat diet containing 20% fish oil for 14 weeks. 3. Systolic blood pressure and fasting blood glucose were markedly increased in the lard group, whereas in the fish oil group they were only transiently increased at the beginning and decreased to levels seen in the control group. 4. Intraperitoneal glucose tolerance test demonstrated that fish oil reversed the impairment of glucose disposal found in the lard group. However, plasma insulin levels were raised transiently at 30 min in the fish oil group compared with the control group. 5. Insulin secretion from pancreatic islets stimulated with glucose in vitro was also enhanced by fish oil. 6. These results lead us to conclude that fish oil improves glucose tolerance by enhancing insulin secretion from pancreatic beta-cells.

Animals↗

Exercise capacity recovers slowly but fully in patients with a left ventricular assist device.

Left ventricular assist devices (LVAD) are used increasingly as bridges to cardiac transplantation. The typical LVAD candidate is a bedridden, critically ill, New York Heart Association (NYHA) Class IV patient with congestive heart failure (CHF) who is dependent upon intravenous, inotropic, and, in many cases, intra-aortic balloon support. The LVAD provides the potential for pre transplant rehabilitation by allowing the patient to become ambulatory, and by improving muscle tone, muscle mass, and nutritional status before transplantation. However, whether the abnormal exercise capacity of these patients improves after implantation has not been elucidated. The purpose of the present study was to evaluate the exercise capacity of patients with CHF after LVAD implantation (n = 10) using peak oxygen consumption during maximal exercise (MVO2), and comparing the results with those of a group of NYHA Class III patients with CHF (n = 14). After 2 months of implantation, MVO2 of the patients with LVAD was 12.8 +/- 0.3 ml/kg/min, which was comparable to that of the NYHA Class III patients with CHF (12.5 +/- 0.5 ml/kg/min). Four of 10 patients with LVAD were monitored for more than 5 months when MVO2 rose to 15.4 +/- 1.0 ml/kg/min (p < 0.05 vs NYHA Class III). In conclusion, the exercise capacity of patients with LVAD recovers slowly but significantly after 5 months of implantation, promising the potential for complete recovery from heart failure in patients supported with an LVAD.

Adult↗

Nitric oxide gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal bypass circuits.

Heparin coated bypass circuits have been reported to improve the biocompatibility of extracorporeal circulation, although it is still insufficient and improvable. Nitric oxide (NO) is known to inhibit platelet activation and inflammatory reactions. In this study, the authors evaluated exogenous NO infusion in enhancing the effect of a heparin coated bypass circuit on the biocompatibility of an extracorporeal circuit, especially in view of the attenuation of the inflammatory response. A miniature closed bypass circuit, including an oxygenator (BioActive surface; Carmeda, Stockholm, Sweden) was primed with fresh human heparinized blood and perfused with a centrifugal pump. Either pure N2 gas (control group: n = 7) or NO gas (NO group [100 ppm in N2]: n = 7) was infused to the oxygenator. NO metabolites (nitrite and nitrate), platelet count, thrombin-antithrombin III complex (TAT), alpha2-plasmin-plasminogen inhibitor complex (PIC), beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), serotonin, complement 3 activation products (C3a), granulocyte elastase, and bradykinin were measured at 0, 30, 60, 120, and 180 min after starting perfusion. At every sampling point, platelet counts were significantly higher, and TAT, beta-TG, and bradykinin were lower in the NO group than in the control group. PF4, C3a, and granulocyte elastase were significantly lower in the NO group at 60, 120, and 180 min. These results suggest that NO gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal circuits.

Biocompatible Materials↗