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Biomedical subjects

Y Minami

Publications and source records attributed to Y Minami.

At least 109 records · Page 6Linked to original sources
PubMed1997

Recombinant interferon-alpha-2a for treatment of chronic hepatitis C: results of a multicenter randomized controlled dose study.

To compare the efficacy of low and relatively high dosages of recombinant interferon (IFN)-alpha-2a in Japanese patients with chronic hepatitis C, as well as to characterize the type of patients who will respond well to a low-dosage treatment, 88 patients with histologically proven chronic hepatitis C were randomly assigned to two treatment groups; one treated with IFN-alpha-2a 6 MU daily for 2 weeks followed by 6 MU three times weekly for 22 weeks (6-MU group), and another given the same initial treatment followed by 3 MU three times weekly for 22 weeks (3-MU group). The rate of sustained normalization of ALT 6 months after the cessation of treatment was 33% in the 3-MU group and 40% in the 6-MU group (p = 0.64). In addition, there was no difference in elimination of serum HCV-RNA 6 months after the cessation of treatment between the 3-MU group (26%) and 6-MU group (29%). Multivariate stepwise regression analysis revealed that serum HCV-RNA level (p = 0.0035) and platelet count (p = 0.0009) were independent variables useful in predicting a sustained response of ALT. The sustained response rate of ALT in patients with a serum HCV-RNA level less than 10(5) copies/ml and serum platelet level above 15 x 10(4)/microliter was 71%, whereas that in patients with a serum HCV-RNA level above 10(5) copies/ml and serum platelet level less than 15 x 10(4)/microliter was 12%. These results indicate that a high rate of sustained response to IFN therapy can be expected in chronic hepatitis C patients with a low serum level of HCV-RNA and a high level of platelets, even if treated with a low dose of IFN.

Antiviral Agents↗
PubMed1997

Dementia-free life expectancy among elderly Japanese.

A 3-year prospective cohort study was conducted to estimate the life expectancy free of dementia (dementia-free life expectancy) in a representative sample of older persons living in an urban Japanese community. For the persons aged 65 years and older, who were not demented at the baseline survey in 1988, mortality and incidence rates of dementia were calculated. At the age of 65 years, males showed a total life expectancy of 18 years, including 16 years free of dementia, and females showed a total life expectancy of 23 years, including 18 years without dementia. At 65 years, the dementia-free life expectancy represented 89% of the total life expectancy for males and 79% for females. Total life expectancy and dementia-free life expectancy were longer among females than among males. However, the life-years with dementia were longer among females. This result would be attributable to a higher incidence of dementia and a lower mortality among females.

Age Distribution↗
PubMed1997

Incidence of hepatocellular carcinoma after interferon therapy in patients with chronic hepatitis C.

We examined the effect of interferon (IFN) therapy for chronic active hepatitis (CAH) C in 207 patients by estimating the incidence of hepatocellular carcinoma (HCC) after IFN therapy using the person-years method. Statistical analysis was performed using the Mantel-Haenszel chi-square test. No HCC was detected in patients with normal serum alanine aminotransferase (ALT) levels after IFN therapy (response-effect group), and in patients with both normal serum ALT levels and hepatitis C virus (HCV)-RNA clearance after IFN therapy (complete-responder group). The incidence per 100,000 person-years in the patients with elevated serum ALT level after IFN therapy (other-effects group) were 1968 and 1624, respectively. The incidence in control patients who did not achieve IFN therapy was 901. No statistically significant differences were observed between the other-effects group, non-responder group, and the control group. Our results so far suggest that normalization of the serum ALT levels and/or HCV clearance might reduce the incidence of HCC.

Adult↗
PubMed1997

Phosphofructokinase interacts with molecular chaperonins GroEL and GroES.

For studying the possible interaction between the chaperonins and phosphofructokinase (PFK), bacterial chaperonins GroEL, GroES, and the PFK were co-purified from chaperonin over-expressing, heat treated E. coli strains. GroEL interacted with PFK in the presence of Mg2+, leading to a gradual decrease in the activity of the enzyme. This type of GroEL-PFK interaction was overcame by the GroES. On the effect of the addition of ATP to the GroEL-PFK complex, the decreased activity of the enzyme was recovered suggesting release of the GroEL-bound enzyme. Contrary to this, in a complete refolding system containing GroEL, GroES, ATP and Mg2+, activity of heat treated bacterial PFK gradually increased showing, that GroEL and GroES together play a role in the folding and/or assembly of PFK. Similar effect of refolding system was also observed on rabbit muscle PFK. The data show that PFK can interact with GroEL, which results in binding of the enzyme; by contrast, GroEL and GroES together has a folding effect leading ultimately to increase of the activity of the enzyme.

Animals↗
PubMed1996

Interleukin-2 (IL-2) upregulates BAG-1 gene expression through serine-rich region within IL-2 receptor beta c chain.

BAG-1 is a Bci-2-binding protein which functions in protection from apoptotic cell death. Here we provide evidence for interleukin-2 (IL-2)-mediated upregulation of BAG-1 expression. In hematopoietic cell line BAF-B03 F7 cells, gene transfer mediated expression of the IL-2R beta c chain is sufficient to confer proliferation and cell survival responses to IL-2. In these IL-2R beta c-expressing cells, BAG-1 mRNA was dramatically induced by IL-2. The IL-2-mediated induction of BAG-1 expression required the activation of tyrosine kinase(s) and was sensitive to rapamycin as the induction of bcl-2 expression was. Analysis of the transfectants which express mutant IL-2R beta c chains or mutant Janus family protein tyrosine kinase Jak3 lacking the kinase domain showed that the IL-2-mediated BAG-1 gene expression required the serinerich region within the IL-2R beta c chain, but Jak3 activation was dispensable. The signaling pathway for BAG-1 gene expression thus highly resembles that for bcl-2 gene expression, strongly suggesting that their induction shares the same signaling pathway. In addition, deletion of the serine-rich region led to loss of IL-2-mediated protection from apoptotic cell death. Taken together, these studies demonstrate that the serine-rich region of the IL-2R beta c chain mediates the coordinated expression of bcl-2 and BAG-1 genes, thereby contributing to suppression of apoptosis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Simultaneous determination of GTS-21 and its metabolite in rat plasma by high-performance liquid chromatography using solid-phase extraction.

It has been suggested that GTS-21 can improve the learning deficits and inhibit the neuro-degeneration in patients with Alzheimer's disease. This paper describes a reversed-phase high-performance liquid chromatographic assay with visible detection at 405 nm for determination of GTS-21 and its metabolite, 4-hydroxy-GTS-21 in rat plasma. The method uses solid-phase extraction with a Bond Elut C18 column. A quantitation limit of 1.0 ng/ml was achieved using 0.5 ml of rat plasma. In the validation study, the coefficients of variation and the relative errors of each compound were less than 10%. Also freeze-thaw and storage stability were confirmed. This method has proved to be applicable to the pharmacokinetic study of GTS-21 in rats.

Animals↗
PubMed1996

GLAST mRNA expression in the periventricular area of experimental hydrocephalus.

Glutamate transporters play an important role in maintaining the extracellular glutamate concentration below the neurotoxic level. We investigated the expression of glutamate/aspartate transporter (GLAST) mRNA in the periventricular region of rats with kaolin-induced hydrocephalus by in situ hybridization (ISH). The density of GLAST mRNA-positive cells and the level of hybridization signals per positive cell significantly increased in the acute stage of hydrocephalus. We also demonstrated co-localization of GLAST mRNA and GFAP immunoreactivity in a single cell using the combined methods of ISH and immunohistochemistry. These findings suggest that GLAST is expressed in the reactive astrocytes of the periventricular area and regulates extracellular glutamate concentration after hydrocephalic brain injury.

Amino Acid Transport System X-AG↗
PubMed1996

Regulation of the heat-shock protein 70 reaction cycle by the mammalian DnaJ homolog, Hsp40.

The effects of the human DnaJ homolog, Hsp40, on the ATPase and chaperone functions of the constitutively expressed Hsp70 homolog, Hsc70, were analyzed. Hsp40 stimulates the hydrolysis of ATP by Hsc70, causing a approximately 7-fold increase in its steady-state ATPase activity. In contrast to the prokaryotic Hsp70 system, ATP-hydrolysis and not the release of bound ADP is the rate-limiting step in the overall ATPase cycle of mammalian Hsc70. The ability to activate the Hsc70 ATPase is partially preserved in a deletion mutant containing the J-domain and the G/F region of Hsp40 but not in a deletion mutant that contains the J-domain alone. As a result of its ATPase stimulating activity, addition of Hsp40 allows Hsc70 to bind peptide in the presence of ATP, whereas in the absence of Hsp40, peptide is efficiently released upon ATP binding to Hsc70. The functional cooperation of Hsp40 with Hsc70 is essential to ensure the ATP hydrolysis-dependent binding of aggregation-sensitive denatured polypeptides, such as thermally denatured firefly luciferase and chemically denatured rhodanese. Binding of these proteins results in the formation of ternary complexes of Hsc70, Hsp40, and substrates. Hsc70 and Hsp40 cooperate with further factors in protein renaturation, as demonstrated by the finding that luciferase, thermally denatured in the presence of Hsc70, Hsp40, and ATP, refolds upon addition of rabbit reticulocyte cytosol. Our results indicate that Hsp40 has a critical regulatory function in the Hsc70 ATPase cycle that is required for the efficient loading of peptide substrate onto Hsc70.

Adenosine Triphosphatases↗
PubMed1996

Cellular localization of Na+/MYO-inositol co-transporter mRNA in the rat brain.

The distribution of Na+/MYO-inositol co-transporter (SMIT) mRNA in the rat brain was studied by in situ hybridization histochemistry. The highest levels of SMIT mRNA were observed in the choroid plexus. Intense hybridization signals were found in the pineal gland, the area postrema, the hippocampus, the locus coeruleus, the suprachiasmatic nucleus, the olfactory bulb and the Purkinje cell and granule cell layers of the cerebellum. Low to moderate levels of labelling were detected in almost all neurones and small glia-like cells throughout the brain. These results suggest that almost all cells in the brain possess an SMIT-mediated osmotic and ionic regulatory system, and uneven densities of positive SMIT mRNA signals may reflect the differences in sensitivity of the cells to osmotic and ionic changes and also reflect differences in permeability of capillaries.

Animals↗
PubMed1996

Heat-induced chaperone activity of HSP90.

The 90-kDa stress protein, HSP90, is a major cytosolic protein ubiquitously distributed in all species. Using two substrate proteins, dihydrofolate reductase (DHFR) and firefly luciferase, we demonstrate here that HSP90 newly acquires a chaperone activity when incubated at temperatures higher than 46 degrees C, which is coupled with self-oligomerization of HSP90. While chemically denatured DHFR refolds spontaneously upon dilution from denaturant, oligomerized HSP90 bound DHFR during the process of refolding and prevented it from renaturation. DHFR was released from the complex with HSP90 by incubating with GroEL/ES complexes in an ATP-dependent manner and refolded into the native form. alpha-Casein inhibited the binding of DHFR to HSP90 and also chased DHFR from the complex with HSP90. These results suggest that HSP90 binds substrates to maintain them in a folding-competent structure. Furthermore, we found that HSP90 prevents luciferase from irreversible thermal denaturation and enables it to refold when postincubated with reticulocyte lysates. This heat-induced chaperone activity of HSP90 associated with its oligomerization may have a pivotal role in protection of cells from thermal damages.

Animals↗
PubMed1996

Expression of Na+/myo-inositol cotransporter mRNA in the inner ear of the rat.

We have demonstrated the cellular localization of Na+/myo-inositol cotransporter (SMIT) mRNA in the rat inner ear by in situ hybridization. In the cochlea, the most intense SMIT mRNA signals were observed in fibrocytes of the spiral ligament, moderate signals were found in the spiral limbus, inner hair cells and spiral ganglion cells, while the hybridization signals were almost undetectable in the marginal cells of the stria vascularis and outer hair cells. In the vestibular system, moderate hybridization signals were found in the sensory epithelium, fibrocytes and vestibular ganglion cells. These findings suggest that SMIT plays an important role in maintenance of intracellular ionic balance and cell volume in the inner ear, especially in the fibrocytes associated with generation of the ion gradients between the endolymph and perilymph.

Animals↗
PubMed1996

Expression of Na+/myo-inositol cotransporter mRNA in normal and hypertonic stress rat eyes.

We studied the localization of Na+/myo-inositol cotransporter (SMIT) mRNA in normal and hypertonic stress rat eyes by in situ hybridization histochemistry using cRNA probes. SMIT mRNA signals were observed in the iris-ciliary body, the lens epithelial cells, and the ganglion cell layer and the inner nuclear layer of the retina. There was a rapid increase on SMIT mRNA in the retina of hypertonic stress rats compared with control rats. These findings suggest that Na+/myo-inositol cotransporter gene expression is osmotically regulated in vivo to protect retinal neuronal function against hypertonic stress.

Animals↗
PubMed1996

Rapid and transient up-regulation of Na+/myo-inositol cotransporter transcription in the brain of acute hypernatremic rats.

The osmoregulatory system is well developed in the brain. Osmolytes contribute to maintenance of cell volume and cellular functions without changing intracellular ionic composition. Myo-inositol is regarded as one of the major osmolytes in the brain. In the present study, we investigated the changes in expressions of sodium myo-inositol cotransporter (SMIT) mRNA in the brain of acute hypernatremic rats by in-situ hybridization and Northern blot methods. Under moderate acute hypernatremic conditions, SMIT mRNA level increased markedly at 1 h and returned to almost control levels at 3 h, in accordance with plasma Na+ concentrations. Especially, distinct increases in SMIT mRNA expression were observed in the granule cells and glial cells in the cerebellum. These findings indicate that SMIT plays an important role in osmoregulation, especially in the early stages of acute hypernatremia in the brain.

Animals↗
PubMed1996

Effect of cardioplegic arrest and reperfusion on coronary reserve and autoregulation.

BACKGROUND: The effects of cardioplegic arrest and reperfusion on the coronary vasculature remain to be characterized. This study was designed to investigate changes in coronary reserve and autoregulation after hypothermic cardioplegic arrest and reperfusion. METHODS: Isolated rabbit hearts were perfused in a retrograde manner with Krebs-Henseleit bicarbonate buffer solution at a pressure of 80 cm H2O. Baseline measurements were performed for (1) coronary flow; (2) vasodilatory response to 5-hydroxytryptamine (10(-7) mol/L) and nitroglycerin (10(-4) mol/L); (3) autoregulatory capacity, quantified as closed-loop gains; and (4) isovolemic left ventricular function. Hearts were then subjected to cardioplegic arrest for 90 minutes. Twenty minutes after reperfusion, measurements were repeated. RESULTS: Coronary flow decreased significantly after reperfusion (6.2 +/- 1.1 versus 5.3 +/- 1.1 mL.min-1.g-1; p < 0.01). The response to 5-hydroxytryptamine as percentage increase of flow decreased significantly after reperfusion (134.0% +/- 12.0% versus 109.1% +/- 6.8%; p < 0.01). However, there was no significant change in the response to nitroglycerin after reperfusion (121.3% +/- 17.6% versus 136.6% +/- 13.3%). The closed-loop gain demonstrated negative values before arrest but became positive after reperfusion, indicating loss of autoregulation after reperfusion. There was no significant change in left ventricular function. CONCLUSIONS: The coronary flow reserve in response to 5-hydroxytryptamine and autoregulation were impaired after cardioplegic arrest and reperfusion, whereas nitroglycerin-induced vasodilatory response and left ventricular function were preserved.

Animals↗
PubMed1996

The independent association of smoking and drinking with serum beta-carotene levels among males in Miyagi, Japan.

BACKGROUND: Previous studies indicated that serum beta-carotene levels were low among smokers and drinkers. However these findings may result from the strong relationship between smoking and drinking. METHODS: Data were collected from 1902 males randomly selected from participants of a cohort study. The effects of smoking on serum beta-carotene levels were assessed according to drinking status (non-drinker, ex-drinker and current drinker), and those of drinking were assessed according to smoking status (ex-smoker and current smoker) using general linear model including other factors (age, intake of green-yellow vegetables, intake of carrot or pumpkin, body mass index serum cholesterol levels.) RESULTS: An inverse dose-response relationship between daily consumption of alcohol and beta-carotene levels was observed regardless of smoking status, and also between number of cigarettes smoked per day and beta-carotene levels regardless of drinking status. CONCLUSION: These results suggest that cigarette smoking and alcohol drinking reduce beta-carotene levels independently.

Adult↗
PubMed1996

A lectin from leaves of Neoregelia flandria recognizes D-glucose, D-mannose and N-acetyl D-glucosamine, differing from the mannose-specific lectins of other monocotyledonous plants.

A mannose-specific lectin was isolated from leaves of Neoregelia flandria, an ornamental plant that belongs to Bromeliaceae, a family of monocotyledons. The amino acid composition and molecular mass of the lectin were similar to those of mannose-specific lectins from other monocotyledons. However, in a test to examine the inhibition of hemagglutination, it became apparent that the isolated lectin recognized D-glucose and N-acetyl D-glucosamine in addition to D-mannose, unlike mannose-specific lectins from the monocotyledons that have been reported to date.

Acetylglucosamine↗