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Biomedical subjects

A Mizuno

Publications and source records attributed to A Mizuno.

At least 91 records · Page 5Linked to original sources
PubMed1998

Identification of a quantitative trait locus influencing plasma insulin levels after 70% pancreatectomy using the OLETF rat.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. The OLETF rat has poor capacity for proliferation of pancreatic beta-cells after partial pancreatectomy, which may be the critical pathogenetic event in NIDDM development. The poor pancreatic beta-cell proliferation in this model is characterized by reduction in beta-cell mass and decrease in insulin content in the remnant pancreas. Our investigation was designed to identify quantitative trait loci (QTLs) responsible for beta-cell mass and plasma insulin levels after partial pancreatectomy by performing a genome-wide scan in an F2 intercross obtained by mating the OLETF and the Fischer-344 (F344) rats. We have identified a suggestive QTL for the plasma insulin levels, near D20Mgh5 on rat chromosome 20, with a maximum lod score of 3.75 which accounts for 20% of the total variance, while no QTLs were detected for beta-cell mass. This chromosome 20 QTL, whose OLETF allele is associated with low plasma insulin levels through acting in an incompletely recessive manner, may affect insulin secretion itself rather than beta-cell proliferation.

Animals↗
PubMed1998

Effect of exercise training and food restriction on endothelium-dependent relaxation in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous NIDDM.

We investigated whether endothelial function may be impaired in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous NIDDM. The effect of exercise training and food restriction on endothelial function was also studied. OLETF rats were divided into three groups at age 16 weeks: sedentary, exercise trained, and food restricted (70% of the food intake of sedentary rats). Otsuka Long-Evans Tokushima rats were used as the age-matched nondiabetic controls. Endothelium-dependent relaxation of the thoracic aorta induced by histamine was significantly attenuated in the sedentary or food-restricted rats, and exercise training improved endothelial function. Relaxation induced by sodium nitroprusside, a donor of nitric oxide, did not differ significantly among groups. Both exercise training and food restriction significantly suppressed plasma levels of glucose and insulin and serum levels of triacylglycerol and cholesterol and reduced the accumulation of abdominal fat. Insulin sensitivity, as measured by the hyperinsulinemic-euglycemic clamp technique, was significantly decreased in sedentary rats but was enhanced in exercise-trained and food-restricted rats. The urinary excretion of nitrite was significantly decreased in sedentary and food-restricted rats compared with nondiabetic rats and was significantly increased in exercise-trained rats. These results indicate that exercise training, but not food restriction, prevents endothelial dysfunction in NIDDM rats, presumably due to the exercise-induced increase in the production of nitric oxide.

Abdomen↗
PubMed1997

Leptin suppresses basal insulin secretion from rat pancreatic islets.

The effects of leptin on insulin secretion from pancreatic islets of Sprague-Dawley rats were examined in vitro. In a basal glucose medium (5.5 mM), insulin secretion from isolated islets was significantly decreased after addition of a recombinant leptin (80 nM) (3.20+/-0.14 nmol/10 islets/h) compared with that before the addition (4.41+/-0.30 nmol/10 islets/h). Although significant leptin suppression of insulin secretion was not observed under a glucose-stimulated (11.1 mM) condition, these results suggest that a negative feedback system may exist between leptin and insulin, which increases the production of leptin from adipose tissues.

Animals↗
PubMed1997

Evaluation of the disintegrin, triflavin, in a rat middle cerebral artery thrombosis model.

Platelet aggregation plays a important role in the thrombotic cerebral infarction. The final common mechanism in the formation of a platelet aggregate is the linking of adjacent platelets by fibrinogen binding to the platelet integrin alpha 11b beta 3. In this study, we evaluated the effect of the disintegrin, triflavin, in a rat middle cerebral artery thrombosis model. Thrombus at the left middle cerebral artery in rat was induced by photochemical reaction between rose bengal and green light, which caused endothelial injury at the site of irradiation. We measured the time to occlusive thrombus formation and the size of ischaemic cerebral damage. Triflavin dose dependently prolonged the time to occlusive thrombus formation in this model. Triflavin also reduced the size of ischaemic cerebral damage on examination at 24 h after photochemical reaction. Triflavin dose dependently inhibited ADP- and collagen-induced platelet aggregation and platelet retention in the collagen-coated beads method ex vivo. These effects were thought to result from the blockade of platelet integrin alpha IIb beta 3. Blockade of platelet integrin alpha IIb beta 3 may be useful in the prevention of cerebral arterial thrombosis.

Animals↗
PubMed1997

Species-specific B-cell epitope on the C-terminal region of the alpha antigen from Mycobacterium scrofulaceum.

In the amino acid (AA) sequences of alpha antigen from mycobacteria, C-terminal regions were variable among a variety of mycobacterial species though the N-terminal regions were relatively conserved. These regions may possess some species-specific antigenic determinants of the alpha antigen from Mycobacterium scrofulaceum (S-alpha). AAs288-300 of S-alpha fused to beta-galactosidase was reactive with the antisera raised against S-alpha. The same fused peptide did not react with the antisera raised against the alpha antigen from Mycobacterium avium (A-alpha) and Mycobacterium bovis BCG (B-alpha). B-cell epitope mapping then was performed focusing on the C-terminal region of S-alpha using the synthetic peptides. Their reactivities with antisera raised against the alpha antigens of three different mycobacterial species were assessed by ELISA. AAs279-286 were a cross-reactive common immunodominant region among three mycobacterial species. This region may be one of the cross-reactive common epitopes in mycobacterial species. And AAs291-300 were reactive only with the antisera raised against S-alpha. This region may possess a species-specific epitope.

Amino Acid Sequence↗
PubMed1997

Endothelial stunning and myocyte recovery after reperfusion of jeopardized muscle: a role of L-arginine blood cardioplegia.

Ischemia and reperfusion may damage myocytes and endothelium in jeopardized hearts. This study tested whether (1) endothelial dysfunction (reduced nitric oxide release) exists despite good contractile performance and (2) supplementation of blood cardioplegic solution with nitric oxide precursor L-arginine augments nitric oxide and restores endothelial function. Among 30 Yorkshire-Duroc pigs, 6 received standard glutamate/aspartate blood cardioplegic solution without global ischemia. Twenty-four underwent 20 minutes of 37 degrees C global ischemia. Six received normal blood reperfusion. In 18, the aortic clamp remained in place 30 more minutes and all received 3 infusions of blood cardioplegic solution. In 6, the blood cardioplegic solution was unaltered; in 6, the blood cardioplegic solution contained L-arginine (a nitric oxide precursor) at 2 mmol/L; in 6, the blood cardioplegic solution contained the nitric oxide synthase inhibitor L-nitro arginine methyl ester (L-NAME) at 1 mmol/L. Complete contractile and endothelial recovery occurred without ischemia. In jeopardized hearts, complete systolic recovery followed infusion of blood cardioplegic solution and of blood cardioplegic solution plus L-arginine. Conversely, contractility recovered approximately 40% after infusion of normal blood and blood cardioplegic solution plus L-NAME. Postischemic nitric oxide production fell 50% in the groups that received blood cardioplegic solution and blood cardioplegic solution plus L-NAME but was increased in the group that received blood cardioplegic solution L-arginine. In vivo endothelium-dependent vasodilator responses to acetylcholine recovered 75% +/- 5% of baseline in the blood cardioplegic solution plus L-arginine group, but less than 20% of baseline in other jeopardized hearts. Endothelium-independent smooth muscle responses to sodium nitroprusside were relatively unaltered. Myeloperoxidase activity (neutrophil accumulation) was similar in the blood cardioplegic solution (without ischemia) and blood cardioplegic solution plus L-arginine groups (0.01 +/- 0.002 vs 0.013 +/- 0.003 microgram/gm tissue). Myeloperoxidase activity was raised substantially to 0.033 +/- 0.002 microgram/gm after exposure to normal blood and to 0.025 +/- 0.003 microgram/gm after infusion of blood cardioplegic solution and was highest at 0.053 +/- 0.01 microgram/gm with exposure to blood cardioplegic solution plus L-NAME in jeopardized hearts. The discrepancy between contractile recovery and endothelial dysfunction in jeopardized muscle can be reversed by adding L-arginine to blood cardioplegic solution.

Animals↗
PubMed1997

Extrapancreatic action of truncated glucagon-like peptide-I in Otsuka Long-Evans Tokushima Fatty rats, an animal model for non-insulin-dependent diabetes mellitus.

To clarify the mechanism(s) of the antidiabetic effects of truncated glucagon-like peptide-1 (GLP-1) in diabetics, we examined its insulinotropic and extrapancreatic effects in a newly established strain of spontaneously non-insulin-dependent diabetic (NIDDM) rats, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, that received a continuous infusion of truncated GLP-1 620 pmol/d/kg (G group, n = 12) or of vehicle (V group, n = 12) for 4 weeks by Alzet pump. Nonfasting plasma glucose levels were significantly lower (P < .05) in the G group than in the V group (7.0 +/- 0.67 v 9.1 +/- 1.7 mmol/L), and fasting plasma immunoreactive insulin (IRI) levels were lower in the former than in the latter (0.63 +/- 0.31 v 0.78 +/- 0.25 nmol/L). At day 15 of infusion, the G group showed an attenuated plasma glucose response to an oral glucose load, but had plasma IRI levels comparable to those in the V group. A long-term infusion of truncated GLP-1 increased the glucose infusion rate (GIR) significantly (P < .05) during a euglycemic-hyperinsulinemic clamp test (59.0 +/- 14.8 mumol/kg/min for group G v 38.9 +/- 12.2 for group V), but hepatic glucose output (HGO) did not differ significantly for either group. Uptake of 2-deoxy-D-glucose (2DG) by peripheral muscles in the G group was as much as 2.4-fold higher than in the V group (5.52 +/- 2.04 v 2.29 +/- 0.97 mumol/100 g muscle weight/min). We conclude from these data that truncated GLP-1, in addition to its well-known incretin effect, is capable of augmenting insulin action in peripheral tissues of diabetics, which can contribute, in part, to improve glucose intolerance in OLETF rats.

Administration, Oral↗
PubMed1997

Exercise training in Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous non-insulin-dependent diabetes mellitus: effects on the B-cell mass, insulin content and fibrosis in the pancreas.

The effects of exercise on alterations in the amount of B-cell mass, insulin content and fibrous tissue present in the pancreas were examined for a diabetic state induced by a 70% pancreatectomy and a prediabetic state in Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model for the spontaneous development of non-insulin-dependent diabetes mellitus (NIDDM). The rats (5-weeks old) were trained either by a 6-week running program or sedentary controls, and at 6-weeks of age, received either a 70% pancreatectomy or a sham-pancreatectomy (sham). As in our previous report, persistent hyperglycemia was detected after surgery for both trained pancreatectomized (Px) and sedentary Px groups. In the nondiabetic sham rats, exercise training resulted in a significantly smaller increase in body weight and beneficial effects on the pancreas as reflected by an increase in pancreatic volume, accompanied by increases in B-cell mass and insulin content as well as less connective tissue in the pancreas compared with the sedentary nondiabetic sham rats. The effect was not sufficient to improve sustained hyperglycemia in the trained diabetic Px rats. This is probably due to a decreased capacity for B-cell proliferation in response to an increased demand for insulin. Although exercise failed to improve this inherent defect in B-cell proliferation, it ameliorated the further deterioration of the pancreas which occurred with hyperglycemia, and resulted in a higher quantity of insulin stored per milligram of B-cell mass (as function of B-cell mass) and less fibrosis in the pancreas, compared with the sedentary diabetic Px rats. The findings of the present study suggest that exercise training has a beneficial effect on the pancreas in the nondiabetic state, and also exerts some positive effects in the diabetic state in this model rat.

Animals↗
PubMed1997

Malignant lymphoma of the mandible: report of a case.

Extranodal malignant lymphoma is relatively rare. When it occurs in the oral region, it is sometimes misdiagnosed as inflammatory disease. This report details a case of malignant lymphoma that involved the fight mandibular region.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Clinical outcome of smoking-cessation trial of nicotine chewing gum evaluated by analysis of nicotine in hair.

The axial distribution of nicotine along the hair shafts was examined in 21 subjects enrolled in a placebo-controlled, double-blind trial of nicotine chewing gum (Nicorette) for validating their self-reported smoking behavior and their physicians' assessments. Hair samples obtained from the subjects once during the 3-month follow-up period (n = 10 for placebo and n = 11 for Nicorette ad libitum) were analyzed for the cm x cm distribution of nicotine along the hair shafts. Hair analysis results were compared with the monthly self-reports and with the plasma concentrations of thiocyanate (SCN-) measured at 1-month intervals. A gradual decrease in nicotine content along the hair shafts generally corresponded to the decrease in self-reported number of cigarettes smoked daily by the subjects who reported that they abstained from smoking or decreased the number of daily cigarettes in placebo and nicotine chewing gum groups. Because nicotine may dissociate slowly from hair follicle cells, nicotine in the hair did not mark a sudden decrease or cessation of smoking and, therefore, hair analysis tended to underestimate the real decrease of smoking. However, physician assessment seemed to depend solely on self-reporting because the time profile of changes in serum SCN- concentration did not correspond necessarily to the changes in the self-reported number of cigarettes used daily.

Adult↗
PubMed1997

Impaired beta-cell function and deposition of fat droplets in the pancreas as a consequence of hypertriglyceridemia in OLETF rat, a model of spontaneous NIDDM.

Hypertriglyceridemia is known to be a feature of obesity-related NIDDM, but the patho-etiological significance of this association is obscure. The effects of triglycerides (TGs) on beta-cell function and morphological changes in pancreas were examined using in vivo and in vitro approaches in male OLETF rats at ages 6, 12, and 30 weeks, with their diabetes-resistant counterpart, LETO rats, as normal controls. The results showed that, in the fasting state, plasma TGs in OLETF rats were increased 2.5-fold at age 6 weeks, 3.3-fold at age 12 weeks, and 6.2-fold at age 30 weeks, compared with age-matched LETO rats. The TG content in islets from 12-week-old OLETF rats was significantly increased when compared with those from their age-matched counterparts, but this was not the case with the 6-week-old OLETF rats. Therefore, the islets from 6-week-old rats were cultured with either free fatty acids (FFAs; 1.0 mmol/l sodium oleate) or TG (5.0 mmol/l Intralipide) for 72 h. Several abnormalities in OLETF rats were evident, in contrast to the results from control LETO rats: 1) glucose-induced insulin secretion was more inhibited by either FFAs or TGs in the presence of 27.7 mmol/l glucose, a result associated, at least in part, with reduced glucokinase activity in the islets; 2) a marked elevation in TG content was found in the islets; and 3) the deposition of fat droplets in the enlarged islets, even in the beta-cells, was found by Oil Red O-insulin double staining at age 30 weeks. In conclusion, hypertriglyceridemia resulted in significant TG stores in the islets, which subsequently inhibited glucose-induced insulin secretion, at least in part, via reduced glucokinase activity in the islets. Fat droplets in islets, therefore, may play an important role in hastening the development of NIDDM in this rat model.

Animals↗
PubMed1997

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents. Special references to bacteria isolated between July 1995 and June 1996].

Isolated bacteria from infections in general surgery during the period from July 1994 to June 1995 were investigated in a multicenter study in Japan, and the following results were obtained. One hundred and sixty-four strains were isolated from primary infections, and 202 strains were isolated from postoperative infections. From primary infections, anaerobic Gram-positive bacteria were predominant, while from post operative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was the highest, followed by that of Staphylococcus aureus from postoperative infections. Among anaerobic Gram-positive bacteria, the isolation rate of Peptostreptococcus spp. was the highest from both types of infections. Among anaerobic Gram-negative, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order, and from postoperative infections, P. aeruginosa was the most predominantly isolated, followed by Enterobacter spp. and Klebsiella spp. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both types of infections. We noticed that MICs of cefazolin against three out of 23 strains of E. coli were higher than 100 micrograms/ml. Among anaerobic bacteria, there were many resistant strains against penicillins and cephems with MICs higher than 100 micrograms/ml, and the same trend was observed among other Bacteroides spp. and Prevotella spp.

Bacterial Infections↗
PubMed1997

[Isolation rate of Enterococcus spp. from surgical infections and their susceptibilities].

Enterococcus spp. isolated from surgical infections during the period from July 1982 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Though the isolation rate of Enterococcus faecalis and other Enterococcus spp. were not high from primary infections, and from postoperative infections the isolation rate of other Enterococcus spp. was also low, the isolation rate of E. faecalis was highest from postoperative infections after 1993. 2. Vancomycin (VCM) showed strongest activity against E. faecalis, and followed by those of ampicillin (ABPC), imipenem. levofloxacin (LVFX) and meropenem in this order. Against other Enterococcus spp., VCM showed strongest activity, and followed by those of ABPC and LVFX. There were no resistant strains against VCM.

Ampicillin↗
PubMed1996

Substitution at codon 269 (glutamine --> proline) of the leptin receptor (OB-R) cDNA is the only mutation found in the Zucker fatty (fa/fa) rat.

We recently cloned one of spliced variant forms of rat leptin receptor (OB-R), which contains a short intracellular domain, and found obese-phenotype-linked nucleotide alteration in the extracellular domain of the cDNA from the Zucker (fa/fa) rat, which results in a glutamine269 to proline269 amino acid substitution. Reported herein are the cloning and sequencing of another spliced variant forms of rat OB-R cDNA with a long intracellular domain. Both forms of OB-R cDNA share the same extracellular domain. In the Zucker (fa/fa) rat, no changes in either the gene structure nor in the nucleotide sequence of the long intracellular domain were observed. However, the expression level of OB-R mRNA in the brain of Zucker (fa/fa) rat was higher than for lean littermates. These facts suggest that the substitution at codon 269 of the OB-R cDNA represents the crucial mutation which results in the obese phenotype of Zucker (fa/fa) rat.

Alternative Splicing↗
PubMed1996

Carnitine transport defect in fibroblasts of juvenile visceral steatosis (JVS) mouse.

Juvenile visceral steatosis (JVS) mice are associated with systemic carnitine deficiency (Kuwajima, et al., 1991). In order to investigate the cause of this deficiency, we compared fibroblast carnitine transport activities in normal mice and JVS mice. The kinetic analysis showed that in formal fibroblasts, the Km and Vmax values for saturable uptake was 15.6 microM and 2.56 pmol/min/mg protein, respectively. In JVS fibroblasts, however, saturable uptake was not observed. There was no great difference in the linear component of uptake between normal and JVS fibroblasts. At the physiological concentration (50 microM) of carnitine, the fibroblast carnitine transport activity in JVS mice was decreased to 18% of that in normal mice. Thus there is hardly any carnitine transport activity in the fibroblasts of JVS mice, indicating that the JVS mouse can be regarded as an animal model of primary carnitine deficiency.

Animals↗
PubMed1996

Mutational analysis of two zinc finger motifs in HIV type 1 nucleocapsid proteins: effects on proteolytic processing of Gag precursors and particle formation.

To clarify the physiological function of two zinc finger motifs in the nucleocapsid (NC) domain of the Gag protein of human immunodeficiency virus type 1 (HIV-1), we changed cysteine to serine in either of the two motifs or both by site-directed mutagenesis. Viral infectivity was lost by any of the mutations, but their effects appeared differently in the respective mutants. Northern blot analysis showed that the first finger mutant was far less efficient (approximately 10% of the wild type) in genomic RNA encapsidation and that the dual mutant of both fingers completely failed to encapsidate the RNA. In contrast, the second finger mutant retained its ability for RNA encapsidation with an efficiency similar to that of the wild type. Immunoblot analysis of the lysates of CD4-positive M8166 cells transfected with the mutant proviral DNAs showed that the processing of Gag precursors was delayed in two mutant viruses having alterations in the first finger sequence, whereas the processing of the second finger mutant appeared to be normal. On the other hand, immunoblot analysis of the virus particles showed that the second finger mutant particles contained some proteins that were thought to be degradation products of p24CA. Electron microscopic observation showed that all particles of these mutant viruses were morphologically alike except that they had a slightly larger diameter than that of the wild type. These results indicate that these finger motifs of HIV-1 NC protein do not function equivalently. Namely, the first finger is primarily responsible for RNA encapsidation and the second is required for stabilization of virus particles.

Amino Acid Sequence↗
PubMed1996

Phenotype-linked amino acid alteration in leptin receptor cDNA from Zucker fatty (fa/fa) rat.

The mouse obese (ob) gene product (leptin), expressed specifically in adipose cells, regulates energy balance in mice. Both mouse diabetes (db) and rat fatty (fa) gene products are thought to play major roles in leptin signaling pathways in the hypothalamic area. Mutations of these genes in murines result in marked obesity and type II diabetes as part of a syndrome that resembles morbid obesity in humans. Reported herein are the cloning and sequencing of one of spliced variant forms of rat leptin receptor (OB-R) cDNA with a short intracellular domain. In the Zucker (fa/fa) rat, no changes in either the gene structure or the expression levels were observed. However phenotype-linked nucleotide alteration exists in the cDNA from Zucker (fa/fa) rat, which results in an amino acid substitution.

Amino Acid Sequence↗