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Y Hamada

Publications and source records attributed to Y Hamada.

At least 19 recordsLinked to original sources
PubMed1995

Na-dependent glutamate transport in high K and high glutathione (HK/HG) and high K and low glutathione (HK/LG) dog red blood cells.

Na-dependent glutamate (Glu) influxes in the red blood cells of normal low K (LK), high K and high glutathione (HK/HG), and high K and low glutathione (HK/LG) dogs were compared. The ranges of the influxes in LK, HK/HG and HK/LG cells were 1.0-63, 62-174 and 1.3-26 mumol/1 cells per h, respectively. Some LK and HK/LG dogs had red blood cells with extremely low Glu influxes. In cells with extremely low Glu influxes, however, there were clear Na-dependent Glu influxes. In LK, HK/HG and HK/LG cells, the Km of Na-dependent Glu influx with respect to the medium Glu concentration were 17, 20 and 19 mM, respectively, and the half-maximal activation (K1/2) with respect to medium Na concentration was 39, 40 and 42 microM, respectively. By the addition of harmaline, a hallucinogenic alkaloid, the Vmax in LK cells was not affected and the Km was increased, while the Vmax was decreased and the Km increased in HK/HG and HK/LG cells. The Ki value with harmaline by means of Dixon plot in LK cells was 5.2 mM, against 1.8 and 1.9 mM in HK/HG and HK/LG cells, respectively. These results suggest that the difference in the Na-dependent Glu influxes between 2 HK groups was due to the varying quantity, not the quality, of the transporter.

ATP-Binding Cassette Transporters↗
PubMed1995

Antigen-driven differentiation of naive Ig-transgenic B cells in vitro.

We have established a culture system in which naive B cells bearing a transgenic, chicken OVA (cOVA)-specific Ig differentiate to plasma cells in vitro after interaction with cOVA plus cOVA-specific helper T cells. B cell-enriched populations from Ig-transgenic mice, but not from nontransgenic mice, proliferated after presenting nanomolar concentrations of cross-linked cOVA to DO11.10 (cOVA plus IAd-specific) T cells. After 6 to 9 days of culture with Ag and specific T cells, the B cells acquired a plasma cell phenotype and secreted the transgene-derived Ig at high levels. Engagement of B cell surface Ig was not essential for primary B cell differentiation. Differentiating B cells enlarged, clustered, and acquired two plasma cell markers, Syndecan and CD43. B cell CD45 isoform expression changed: the B220 isoform was lost in a T cell-dependent manner, whereas the CD45RB isoform was gained in a T-independent manner. Although unstimulated B cells survived less than 72 h in vitro, those in Ag-stimulated cultures showed reduced early death, a surge of proliferation at 3 to 5 days, and increased death late in the culture. Using a large population of naive B cells of defined antigenic specificity permits us to study a primary immune response to an Ag, rather than to less physiologic polyclonal stimuli. Because all steps of differentiation occurred in vitro, they are easily accessible for study. This coculture system provides an opportunity to observe Ag-specific T cell-B cell collaboration.

Animals↗
PubMed1995

Absorption of new HIV-1 protease inhibitor, KNI-272, after intraduodenal and intragastric administrations to rats: effect of solvent.

KNI-272 is a tripeptide drug that has a strong pharmacological potential for treating human immunodeficiency virus type 1 (HIV-1). We have already reported the pharmacokinetic characteristics of KNI-272 after intravenous and intraduodenal (ID) administrations to rats. In this study, KNI-272 was administered to rats as a solution and the effect of four kinds of solvent on the bioavailability (BA) of KNI-272 was determined using rats. The mixtures included propylene glycol (PG) and water (70% PG), a solution of PG (100% PG), a solution of Tween 80 (Tween 80), and a mixture of PG and HCO60, a polyoxyethylated, 60 mumol, castor oil derivative (PG:HCO60 = 7:3). After ID administration to rats at a dose of 50.0 mg kg-1, the mean peak plasma concentrations, Cmax, were 2.58 +/- 0.53 (SE) (70% PG), 3.28 +/- 0.51 (100% PG), 3.15 +/- 0.51 (Tween 80), and 4.66 +/- 0.68 micrograms mL-1 (PG:HCO60). The highest BA, 44.6%, was obtained after ID administration of KNI-272 dissolved in PG:HCO60. On the other hand, after intragastric (IG) administration of KNI-272 solution in which the drug was dissolved with PG:HCO60, the Tmax, the Cmax, and the BA were 1.25 +/- 0.60 h, 2.33 +/- 0.65 micrograms mL-1, and 24.2%, respectively. The Cmax and BA values were equal to half of the values obtained after ID administration of KNI-272 dissolved in the same solution. In this study, as the PG concentration in the solution increased and the other additives (Tween 80 and HCO60) were coadministered, the BA of KNI-272 after ID administration increased. These results suggest that, for the development of an oral dosage form of KNI-272, a non-ionic surfactant that dissolves in the duodenum or small intestine and that enhances the absorption of this drug from the gastrointestinal tract into the enterocytes is needed.

Administration, Oral↗
PubMed1995

Conformational analysis of dolastatin 10: an NMR and theoretical approach.

A solution conformational analysis of dolastatin 10, a powerful antineoplastic agent, has been carried out by means of nmr techniques and theoretical calculations. 1H mono- and bidimensional nmr experiments, as well as 1H-13C heterocorrelated spectra, have been performed on CD2Cl2 solutions. The most interesting nmr data is a huge shielding of the aCH(25) proton of the Dov residue, suggesting the presence of an interaction between the N-terminal and the aromatic C-terminal ends of the molecule. The possibility of a head-to-tail intermolecular association having been discarded, the presence of a series of preferred folded conformation has been hypothesized. Conformational theoretical analysis supports the nmr hypothesis of a folded peptide-like molecule, and a series of possible conformers in good agreement with the experimental data have been analyzed.

Amino Acid Sequence↗
PubMed1995

A mutation in the glucagon receptor gene (Gly40Ser): heterogeneity in the association with diabetes mellitus.

A possible pathogenic mutation in the glucagon receptor gene causing a Gly to Ser change at codon 40 (Gly40Ser) was reported to be associated and linked with non-insulin-dependent diabetes mellitus (NIDDM), in France and Sardinia. Since the frequency of the mutation (Gly40Ser), about 5% in the French population of familial NIDDM and 8% in randomly chosen diabetic patients in Sardinia, was much higher than that of any of the previously reported mutations in candidate genes, it is important to clarify whether the contribution of this mutation to NIDDM is universal. In this study, we investigated the association of this mutation with diabetes mellitus in a large number of Japanese diabetic patients (383 NIDDM and 53 insulin-dependent diabetic patients) by polymerase chain reaction-restriction fragment length polymorphism analysis. None of the Japanese diabetic patients showed Gly40Ser mutation and the association of this mutation with NIDDM was significantly different (p < 4.10(-5) vs French, p < 3.10(-6) vs Sardinian by Fisher's exact test). The results not only indicate that the mutation plays little, if any, role in susceptibility to diabetes in Japan, but also indicate the genetic heterogeneity in NIDDM and further emphasize the importance of studies on genetic susceptibility to NIDDM and other complex traits in different ethnic groups.

Adolescent↗
PubMed1995

Spiral computed tomography for biliary dilatation.

Spiral computed tomography (SCT), which consists of rapid volumetric data acquisition and planar image display, was performed on 12 patients with biliary dilatation after excisional procedure. The technique was evaluated for image quality and impact on clinical practice. All patients safely underwent SCT scanning after intravenous cholangiography (IVC) without any sedations. In 11 of 12 patients reliable biliary images were obtained and three-dimensional (3D) reconstruction images of the biliary system with bilioenteric anastomosis were generally of diagnostic quality even in young children. As a consequence, IVC-SCT technique appears to have the potential for improving the efficacy and safety of diagnostic CT in investigation of the biliary system. In particular, this technique may be useful for detecting bilioenteric anastomotic conditions in follow-up studies of pediatric patients with biliary dilatation.

Adolescent↗
PubMed1995

Effects of an aldose reductase inhibitor on erythrocyte fructose 3-phosphate and sorbitol 3-phosphate levels in diabetic patients.

Fructose 3-phosphate and sorbitol 3-phosphate are novel metabolites that have been shown to associate with the polyol pathway in animal experiments. Fructose 3-phosphate is of particular interest because of its potent glycation capability as compared with other glycolytic intermediates, e.g., fructose. We observed the effects of treatment with epalrestat, an aldose reductase inhibitor, on their concentrations in erythrocytes from diabetic patients. The levels of both metabolites were significantly higher in diabetic patients than in non-diabetic subjects. A group of patients who had been treated with epalrestat showed significantly lower levels of both metabolites as compared with those untreated. A treatment of three patients with epalrestat for one month resulted in obvious decreases in their concentrations. The results suggest a possible explanation for the preventive effect of an aldose reductase inhibitor on nonenzymatic glycation.

Adult↗
PubMed1995

Neurotropin prevents neurophysiological abnormalities and ADP-induced hyperaggregability in rats with streptozotocin-induced diabetes.

Neurotropin, a non-proteinaceous extract from the inflamed dermis of rabbits inoculated with vaccinia virus, was administered for 8 weeks to rats with streptozotocin-induced diabetes. The physiological and biochemical changes of the nerves were studied as well as ADP-induced platelet aggregation. Neurotropin improved the caudal motor nerve conduction velocity, R-R variability, sciatic nerve blood flow, and platelet hyperaggregability in diabetic rats, despite having no effect on sorbitol and fructose accumulation or myoinositol depletion in the sciatic nerve. The correlation between nerve conduction velocity, R-R variability, nerve blood flow, and platelet aggregation were significant between each two parameters (p < 0.0001). Thus, the mechanism of action of neurotropin differed from that of aldose reductase inhibitors. These findings suggest that vascular factors may play an important role in the development of diabetic neuropathy, and that neurotropin may be useful for the treatment of this condition.

Adenosine Diphosphate↗
PubMed1995

Prevention of abnormalities in motor nerve conduction and nerve blood-flow by a prostacyclin analog, beraprost sodium, in streptozotocin-induced diabetic rats.

The effects of the prostacyclin analog beraprost sodium on motor nerve function and nerve blood-flow were examined in streptozotocin-induced diabetic rats. Oral administration of beraprost sodium 0.1 mg/kg/day for 8 wks significantly (P < 0.001) improved caudal motor nerve conduction velocity and sciatic nerve blood-flow, both of which are impaired in diabetic rats. Beraprost sodium did not affect glucose, sorbitol, or fructose levels in the sciatic nerve. However, a decreased content of cyclic AMP in the sciatic nerve and higher level of thromboxane B2 in the thoracic aorta of diabetic rats, as compared with those in normal rats, were reversed by the treatment with beraprost sodium (P < 0.01). Results suggest that beraprost sodium may have value in treating diabetic neuropathy, mainly by improving endoneurial blood-flow.

Animals↗
PubMed1995

Effect of a potent new aldose reductase inhibitor, (5-(3-thienyltetrazol-1-yl)acetic acid (TAT), on diabetic neuropathy in rats.

(5-(3-Thienyl)tetrazol-1-yl)acetic acid (TAT), a novel potent aldose reductase inhibitor, was administered for 4 weeks to rats with streptozotocin-induced diabetes. Physiological and biochemical studies were subsequently conducted on rat nerve tissue and erythrocyte sorbitol content was estimated. Sciatic nerve blood flow (SNBF) was markedly lower (about 43.4%) in untreated diabetic (DC) rats than in non-diabetic controls (NC). A significant delay in caudal motor nerve conduction velocity (MNCV) and significantly higher glucose, sorbitol and fructose values were observed in the sciatic nerve, accompanied by a markedly higher sorbitol concentration in erythrocytes. In contrast, TAT-treated diabetic groups (DT-10, DT-40 and DT-200) had significantly higher SNBF, MNCV and sciatic nerve myo-inositol values and lower sciatic nerve sorbitol and fructose levels and erythrocyte sorbitol concentration than the DC group. There were good correlations between SNBF and MNCV (r = 0.672, P < 0.001) and between SNBF and erythrocyte sorbitol (r = 0.455, P < 0.003). These findings suggest that both vascular and metabolic factors play an important role in diabetic neuropathy and the effect of aldose reductase inhibitors on diabetic neuropathy may be mediated by at least these two factors.

Aldehyde Reductase↗
PubMed1995

Differential expression of Notch1 and Notch2 in developing and adult mouse brain.

The Notch gene encodes a large transmembrane protein, and is required for the correct differentiation of both neural and non-neural tissues in Drosophila. Mammals have more than one Notch gene homolog, e.g. Notch1 and Notch2. Here, in order to determine the role of Notch genes in the mouse nervous system, we used in situ hybridization to study the expression of the Notch1 and -2 genes through mouse embryogenesis and into adulthood. The expression of Notch1 and Notch2 differed throughout development. Notch2 was expressed in the embryonic ventricular zone, the postnatal ependymal cells, and the choroid plexus throughout embryonic and postnatal development. Notch1 was also expressed in the ventricular zone between embryonic days 10 and 14, but its expression decreased gradually as embryos developed. The postnatal mouse brain strongly expressed Notch2, but not Notch1, in the granular cell layer of hippocampal dentate gyrus, where neurogenesis continues even in adult rodents. The most remarkable finding was the detection of a strong signal for Notch2 mRNA in two circumventricular organs: the subfornical organ and the area postrema. The receptor encoded by the Notch2 gene, which is located in these areas, may respond to unknown ligands in CSF. This putative receptor may participate in signal transduction by way of both neural and humoral links. These data suggest that Notch2, rather than Notch1, is related not only to development, but also to some postnatal functions of mouse central nervous system.

Animals↗
PubMed1995

[A case of toxic shock-like syndrome due to Streptococcus pyogenes].

A case of toxic-shock syndrome due to Streptococcus pyogenes is reported. A 76-year-old female was admitted with complaints of fevers and chills. She had been suffering from cellulitis on her right dorsum pedis for 7 months. Laboratory data on admission showed elevated values of WBC, CRP, and dysfunction of the liver and kidney. She was diagnosed as sepsis due to the cellulitis, and was treated with PIPC and FMOX. However, several hours after admission, her blood pressure decreased and oliguria appeared. Bacteriological examinations from the blood and the cellulitis revealed group A beta-hemolytic Streptococcus which gave streptococcal pyrogenic exotoxin (T-28, SPE.B + C). She died 23 hours after her admission in spite of changing antibiotics to a high-dose of PC-G therapy. This is one of the rare cases of toxic shock-like syndrome due to Streptococcus pyogenes from the cellulitis of the dorsum pedis.

Aged↗
PubMed1995

Insulin receptor gene polymorphism and hyperinsulinemia in hypertensive patients.

Although insulin resistance often occurs in association with hypertension, considerable variation is observed in the degree of insulin resistance among hypertensive patients. Since there is evidence of a genetic basis in the development of insulin resistance in hypertension, we analyzed the contribution of genetic factors to insulin resistance in hypertensive patients. Sixty-six Japanese hypertensive patients were studied. These patients were divided into two groups (hyperinsulinemia group and normoinsulinemia group) according to plasma insulin response during a 75-g oral glucose tolerance test (75g-OGTT). Insulin receptor gene (INSR) was studied for association with insulin resistance in hypertensive patients. A microsatellite polymorphism in intron-2 of the insulin receptor gene was analyzed by the polymerase chain reaction method. Five alleles were detected in the INSR microsatellite. The frequency of C/C genotype in the hyperinsulinemia group was significantly higher than that in the normoinsulinemia group (73% vs. 43%, p = 0.02). There was no difference in genotype frequency of INSR between hypertensive patients and control subjects. When the hypertensive patients were divided into two groups, the frequency of C/C genotype in the hyperinsulinemia group was significantly higher than that in the control group (73% vs. 45%, p = 0.014). There was no significant difference between the normoinsulinemia group and control group. These data suggest that the insulin receptor gene may contribute to insulin resistance in hypertensive patients with hyperinsulinemia.

Alleles↗
PubMed1995

Aspergillus aneurysm of the middle cerebral artery causing a fatal subarachnoid hemorrhage.

A rare case of Aspergillus aneurysm of the central nervous system (CNS) leading to subarachnoid hemorrhage (SAH) is reported. An 83-year-old woman developed visual disturbance and headache. Computed tomographic scans showed no evidence of aneurysm or tumor in the intracranium. She suddenly died from SAH. Autopsy revealed massive SAH due to ruptured Aspergillus aneurysm of the middle cerebral artery. Aspergillus was suggested to have extended from the paranasal sinuses. Aspergillosis of CNS should be considered in patients with neurological symptoms such as visual disturbance and trigeminal neuralgia, especially in cases of the aged or immunocompromised.

Aged↗
PubMed1995

Angiotensin I-converting enzyme gene polymorphism is associated with myocardial infarction, but not with retinopathy or nephropathy, in NIDDM.

OBJECTIVE: To clarify the relationship between the angiotensin I-converting enzyme (ACE) gene polymorphism and diabetic micro- and macroangiopathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: We examined 267 NIDDM patients with various stages of diabetic retinopathy, 61 patients with myocardial infarction (MI), and 136 patients without MI. An insertion/deletion polymorphism of the ACE gene was typed by polymerase chain reaction. RESULTS: Although no association was found between ACE gene polymorphism and diabetic retinopathy or nephropathy, this polymorphism was associated with MI in the patients with NIDDM. Homozygotes for the deletion polymorphism (DD genotype) were found more frequently in diabetic patients with MI (31.1%) than in diabetic patients without ischemic heart disease (16.9%), with a relative risk of 2.22 (95% confidence interval 1.11-4.46, P = 0.024). CONCLUSION: These data indicate that ACE gene polymorphism is associated with MI, but not with retinopathy or nephropathy, in patients with NIDDM and suggest that the ACE gene confers susceptibility to diabetic macroangiopathy but not to microangiopathy.

Alleles↗
PubMed1995

An aldose reductase inhibitor, TAT, reduces ADP-induced platelet hyperaggregation in streptozotocin-induced diabetic rats with neuropathy.

To investigate the relationship between metabolic and vascular factors, especially polyol pathway and platelet aggregation, in the pathogenesis of diabetic neuropathy, the effects of a novel potent aldose reductase inhibitor, TAT ((5-(3-thienyl) tetrazol-1-yl) acetic acid monohydrate) on adenosine diphosphate-induced platelet aggregation, polyol contents in platelets, motor nerve conduction velocity (MNCV), and sciatic nerve blood flow (SNBF) were examined in streptozotocin-induced diabetic rats. Diabetic rats demonstrated hyperaggregation in response to adenosine diphosphate, accompanied by sorbitol and fructose accumulation and myoinositol depletion in platelets. Treatment with TAT improved these abnormalities in diabetic rats. A delayed MNCV and a reduced SNBF in diabetic rats were normalized by the administration of TAT. These observations suggest that increased polyol pathway activity plays an important role in platelet aggregation in the development of diabetic neuropathy and that aldose reductase inhibitor is useful for the treatment of diabetic neuropathy from the viewpoint not only of metabolic factors but also of vascular factors.

Adenosine Diphosphate↗
PubMed1995

[Role of interstitium in the regulation of renal tubular solute transport].

The physiological significance of the renal interstitium is reviewed with special reference to solute transport. The renal tubules and vasculatures participate in essential parts of the nephron functions. The renal interstitium, interposing among these structures, regulates solute transport across the renal tubules. In the renal cortex, changes in the interstitial pressure modulate the proximal tubular fluid reabsorption via paracellular shunt pathways. In the renal medulla, the interstitium may play an important role in the lateral diffusion of solutes and water, contributing to the mechanisms of urine concentration, as well as, medullary potassium recycling and ammonia excretion.

Animals↗