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Biomedical subjects

Y Hamada

Publications and source records attributed to Y Hamada.

At least 235 records · Page 13Linked to original sources

Increased alanine uptake and lipid synthesis from alanine in isolated hepatocytes of Wistar-Kyoto fatty rats: an inhibitory effect of biguanides.

To examine the pathophysiological characteristics of non-insulin-dependent diabetes mellitus, alanine metabolism in isolated hepatocytes of male Wistar-Kyoto (WKY) fatty rats (genetically obese and hyperglycemic) and their lean littermates was investigated. The effects of glucagon and the biguanides, metformin and buformin, on alanine metabolism were also studied by measuring alanine uptake and lipid synthesis from alanine. WKY fatty rats showed higher plasma insulin and lipid concentrations than lean rats at 5 as well as at 12 weeks of age. Alanine uptake into hepatocytes was increased in fatty rats only at 12 weeks of age compared with lean rats. Lipid synthesis from alanine in hepatocytes was increased in fatty rats at 5 and 12 weeks of age compared with lean rats. Glucagon increased alanine uptake into hepatocytes but did not affect lipid synthesis from alanine in both fatty and lean rats. Low concentrations (0.1 mM) of biguanides decreased lipid synthesis from alanine only in fatty rats without inhibiting alanine uptake into hepatocytes. These observations suggest that lipid synthesis from alanine in hepatocytes of WKY fatty rats is accelerated prior to the onset of diabetes mellitus, which might be associated with the development of diabetes, and that an inhibitory effect on increased lipid synthesis is one of the pharmacodynamic actions of biguanides.

Aging↗

[Insulin, as a regulating factor of blood pressure].

In patients with hypertension, insulin resistance and hyperinsulinemia are more prevalent than in normal individuals. Furthermore, the prevalence of hypertension in diabetic patients is higher than in nondiabetic individuals. Insulin resistance has been implicated in the common mechanisms underlying diabetes, hypertension, hyperlipidemia and obesity. A number of mechanisms have been proposed to account for the elevation of BP secondary to hyperinsulinemia, such as 1) increased tubular reabsorption of sodium ions, 2) increased intracellular sodium and calcium ions, 3) increased sympathetic nervous activity, and 4) proliferation of vascular smooth muscle cells. Moreover, hypertension was reported to be a possible cause of insulin resistance. The detailed mechanism of insulin leading hypertension are still under investigation.

Animals↗

[Life-threatening ventricular tachyarrhythmia after CABG in a patient with poor LV function--an experience with the implantable cardioverter defibrillator].

A 52-year-old man with reduced left ventricular function (ejection fraction 0.27) due to myocardial infarction, underwent coronary artery bypass grafting (CABG; LITA-LAD, free RITA-4PD) for angina pectoris. He had suffered from recurrent sustained ventricular tachycardia (VT) since 5 hours after CABG. This arrhythmia was resistant to various antiarrhythmic agents such as Lidocaine, Mexiletine, Disopyramide, Procainamide and Propafenone. He required mechanical circulatory supports (intra-aortic balloon pumping and percutaneous cardiopulmonary support) for the maintenance of hemodynamics during repeated VT that required cardioversions of a total of 441 times during 18 days. Following the administration of Amiodarone, the VT was successfully suppressed. However, he had repeated episodes of VT on exercise, thus, he underwent insertion of the implantable cardioverter-defibrillator at the 98 post-operative day, and he was successfully discharged at the 134 post-operative day after CABG. The instrument was verified to be normal in function after the VT induction test.

Coronary Artery Bypass↗

Rapid formation of advanced glycation end products by intermediate metabolites of glycolytic pathway and polyol pathway.

To clarify roles of intermediate metabolites of the glycolytic pathway and the polyol pathway in nonenzymatic glycation under physiological conditions, we incubated bovine serum albumin with intermediates of both pathways in the micromolar range as well as with 20 mmol/l glucose, and observed the formation of advanced glycation end products (AGEs). We found that triose phosphates, glyceraldehyde, and a novel polyol pathway-related metabolite, fructose 3-phosphate along with its breakdown product, 3-deoxyglucosone were extremely potent glycating agents that at nearly physiological concentrations on incubation with albumin produced substantial amounts of AGEs as early as 24 hours, while 20 mmol/l glucose afforded trace amounts of AGEs after two week incubation. The results along with the previous evidence of the increased level of intermediates in diabetic states may suggest that the intermediate metabolites rather than glucose contribute to enhanced glycation in diabetic tissues, inspite of the much lower concentrations compared with glucose.

Animals↗

Functional conservation of mouse Notch receptor family members.

All the known members of the mouse Notch receptor family were examined for their biochemical function by interaction with a DNA binding protein RBP-Jkappa. mNotch2, mNotch3 and int3 (= mNotch4) were shown to interact with RBP-Jkappa by the GST-fusion pull down assay and dominant negative competition with Epstein Barr virus nuclear antigen 2. Furthermore the intracellular region of int3 was shown to transactivate the Epstein Barr virus TP1 promoter. These results indicate that all mouse Notch family members have biochemical functions similar to mNotch1, which transduces proliferative signal by direct interaction with the DNA binding protein RBP-Jkappa.

Amino Acid Sequence↗

Nerve function and blood flow in Otsuka Long-Evans Tokushima Fatty rats with sucrose feeding: effect of an anticoagulant.

To investigate the pathogenesis of diabetic neuropathy in non-insulin-dependent diabetes mellitus, Otsuka Long-Evans Tokushima Fatty rats, an animal model of non-insulin-dependent diabetes mellitus, and non-diabetic Long-Evans Tokushima Otsuka rats were fed with or without sucrose and/or cilostazol, an anticoagulant, for 8 weeks. Sucrose-fed diabetic rats showed a delayed motor nerve conduction velocity, decreased R-R interval variability of electrocardiogram, reduced sciatic nerve blood flow, increased platelet aggregability and a decreased erythrocyte 2,3-diphosphoglycerate concentration compared with non-sucrose-fed diabetic rats and non-diabetic rats. These abnormalities were significantly prevented by treatment with cilostazol without changes in the nerve tissue levels of polyols. These findings indicate that sucrose-fed Otsuka Long-Evans Tokushima Fatty rats may be a useful animal model of neuropathy in non-insulin-dependent diabetes mellitus, and that cilostazol may prevent the development of diabetic neuropathy by modifying vascular factors.

2,3-Diphosphoglycerate↗

The 'functional connection' of neurones in relation to behavioural states in rats.

In order to investigate whether dynamics of neuronal networks change during differing behavioural states, the 'functional connection' between neurones in the rat vibrissal sensorimotor system during two different behavioural states (active vs passive whiskering) were revealed using time-dependent scatter diagrams. The functional connection between neurones in the vibrissal motor (MCx) and sensory (SCx) cortices and the superior colliculus (SC) changed depending on the behavioural state. In the rat vibrissal system, the pattern of correlated activities among neurones in the MCx, SCx and SC may play an important role in determining behaviour.

Animals↗

Induction and its spread of apoptosis in rat spinal cord after mechanical trauma.

This study was undertaken to examine the spinal cord of rats after trauma for the induction of apoptosis. DNA ladder formation was demonstrated by gel electrophoresis of the DNA obtained from the spinal cord at the site of injury after trauma from 12 h to 8 days and was most significant on Days 3 and 4. As for the longitudinal spread of the injury in the spinal cord, the ladder formation was observed in the two segments adjacent to the site of trauma 3 days after trauma. Histological examination using in situ end labeling also demonstrated the appearance of apoptosis. These results provide the evidence for the induction of apoptosis in the spinal cord after trauma in rats.

Animals↗

Effect of propionyl-L-carnitine on oscillatory potentials in electroretinogram in streptozotocin-diabetic rats.

The effect of propionyl-L-carnitine, an analogue of L-carnitine, and insulin on the oscillatory potentials of the electroretinogram was determined in rats with streptozotocin-induced diabetes. Propionyl-L-carnitine was administered at a daily dose of 0.5 g/kg by gavage for 4 weeks, while other rats were treated with subcutaneous injections of insulin (8-10 U/day). Both treatments shortened the peak latencies of the oscillatory potentials in the electroretinogram, which were significantly prolonged in untreated diabetic rats (O1, O2 and O3, and sigma (O1 + O2 + O3)) (P < 0.0001 vs. untreated normal rats). A significant decrease in the erythrocyte free carnitine level in diabetic rats was prevented by both treatments. Insulin produced a significant reduction of retinal glucose, sorbitol and fructose levels in diabetic rats, while propionyl-L-carnitine failed to do so. However, both treatments markedly reduced serum lipids levels in the diabetic rats. These findings provide information on the pathogenesis of diabetic retinopathy as well as suggesting the potential therapeutic value of propionyl-L-carnitine for retinopathy.

Analysis of Variance↗

Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control.

We have studied the initial development of pluripotent gut endoderm to hepatocytes using a tissue explant system from mouse embryos. We not only find cellular interactions that specify hepatic differentiation but also those that block hepatogenesis in regions of the endoderm that normally give rise to other tissues. The results implicate both positive and negative signaling in early hepatic specification. In vivo footprinting of the albumin enhancer in precursor gut endoderm shows that the transcriptionally silent but potentially active chromatin is characterized by occupancy of an HNF-3 site. Upon hepatic specification, a host of other factors bind nearby sites as the gene becomes active. Genes in pluripotent cells therefore may be marked for potential expression by entry points in chromatin, where additional factors bind during cell type specification. The findings also provide insight into the evolutionary origin of different endodermal cell types.

Actins↗

Effects of exogenous transforming growth factor-beta 1 on spinal cord injury in rats.

This study was undertaken to examine the effect of transforming growth factor-beta 1 (TGF-beta 1) administered into the subarachnoid space after spinal cord injury (SCI) on the increased production of inducible-nitric oxide synthase (i-NOS) in the injured spinal cord in rats. The expression of i-NOS mRNA after SCI was remarkably down-regulated by TGF-beta 1 in vivo. Rats treated with TGF-beta 1 showed a better outcome regarding hindlimb motor dysfunction in the first 5 days after injury compared to the saline-treated rats. However, the final outcome was not better and fibrous scar formation in the injured spinal cord was more evident, which was demonstrated as increased immunoreactivity of fibronectin in the later stage after SCI. These results provide evidence of both positive and negative contributions of TGF-beta 1 to the pathology associated with SCI.

Animals↗

Successful treatment of Wolff-Parkinson-White syndrome with concomitant mitral stenosis by simultaneous surgery.

We report the case of a 61-year-old man with type B Wolff-Parkinson-White (WPW) syndrome associated with a right atrioventricular (AV) accessory pathway and concomitant mitral stenosis, who underwent successful operative treatment by simultaneous surgery. His preoperative course had been characterized by cardiac failure and repeated episodes of atrial tachyarrhythmia, in the form of fibrillation and flutter, which were difficult to control by conventional medication. Preoperative electrocardiograms (ECGs) had suggested that the accessory pathway was located in the right posterior to posteroseptal wall; however, at the time of surgery, epicardial electrophysiological mapping with sock electrodes revealed a preexcitation area in the AV groove at the lateral right margin of the heart. This discrepancy was thought to have been due to the presence of mitral stenosis or multiple accessory pathways. Thus, division and cryoablation of the accessory pathway by an endocardial approach, in addition to mitral valve replacement, were performed under cardiopulmonary bypass. His postoperative course was uneventful, and subsequent ECGs revealed that the delta waves had disappeared. The successful outcome of this patient demonstrates the effectiveness of simultaneous surgery for WPW syndrome associated with valvular disease.

Atrial Fibrillation↗

Anorectal stenosis in a neonate: report of a case and review of the Japanese literature.

We report herein the case of an infant with anorectal stenosis successfully treated by staged surgery. At 1 day of age, the anal orifice showed circumferential stenosis located 5 mm from the anal verge and extending into the anal canal for approximately 1 cm; however, no hypertrophic raphe or bucket handle appearance were observed, and no associated anomalies such as a presacral mass or sacral dysgenesis were found. At 2 days of age, the infant underwent a sigmoid colostomy under the diagnosis of low anorectal stenosis, followed by a successful anorectoplasty, performed through a sacroperineal approach when he was 8 months old. An analysis of 13 other cases of anorectal stenosis from the Japanese literature indicates that this type of malformation should be treated by staged surgery, as an initial colostomy in the neonatal period, followed by anorectoplasty through a sacroperineal approach during infancy.

Anus Diseases↗

Association of Trp64Arg mutation of the beta3-adrenergic-receptor with NIDDM and body weight gain.

A possible pathogenic mutation in the beta 3-adrenergic-receptor gene (Trp64Arg) has been reported to be associated with an earlier age of onset of non-insulin-dependent diabetes mellitus (NIDDM) and clinical features of the insulin resistance syndrome in Pima Indian, Finnish and French subjects. Since marked heterogeneity has been reported in the association of mutations of candidate genes with NIDDM between Japanese and other ethnic groups, we investigated the association of Trp64Arg with NIDDM in Japanese subjects. The allele frequency of the mutation (Arg) was slightly, but not significantly, higher in NIDDM than in control subjects (70 out of 342 alleles [20.5%] vs 40 out of 248 [16.1%], respectively, p > 0.2). When our data were combined with those of Pima Indian and Finnish subjects, however, the Arg/Arg genotype was significantly associated with NIDDM as compared with the other two genotypes (p < 0.005, relative risk [RR] 2.13, 95% confidence interval [CI] 1.28-3.55). The Arg allele was also associated with NIDDM (p < 0.05, RR 1.27, 95% CI 1.06-1.52). Japanese subjects homozygous for the mutation had a significantly higher body mass index (mean +/- SD: 25.5 +/- 3.9 kg/m2) than heterozygotes (22.6 +/- 4.1, p < 0.05) and normal homozygotes (22.8 +/- 3.8, p < 0.05). NIDDM patients homozygous for the mutation tended to have an earlier age of onset of NIDDM than those with other genotypes. These data suggest that the Trp64Arg mutation not only contributes to weight gain and age-at-onset of NIDDM but is also associated with susceptibility to NIDDM.

Age of Onset↗