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Biomedical subjects

S Matsushima

Publications and source records attributed to S Matsushima.

At least 37 records · Page 2Linked to original sources
PubMed1999

Decrease in the prevalence of IL-4-producing CD4+ T cells in patients with advanced stage of primary biliary cirrhosis.

OBJECTIVE: To elucidate the precise immunological features in primary biliary cirrhosis (PBC), we examined the relative prevalence of CD4+ T cells in either symptomatic PBC (sPBC) or asymptomatic PBC patients (aPBC), and furthermore, these results were compared with their histological features. METHODS: Cytokine synthesis of peripheral blood mononuclear cells obtained from 24 PBC patients (9 sPBC and 15 aPBC) were examined by intracellular staining method. The relative prevalence of three distinct CD4+ T cells, gamma-interferon (IFN-gamma)-producing cells (Th1), interleukin-4 (IL-4)-producing cells (Th2), and the cells producing both IL-4 and IFN-gamma (Th0), was analyzed by FACScan and compared with those of closely age-matched healthy and disease controls. RESULTS: The results demonstrated that although a significant difference was not observed in the prevalence of Th1 or Th0, a remarkable difference was observed in the prevalence of Th2 (1.2+/-0.7 in sPBC, 4.1+/-1.3 in healthy subjects, 4.1+/-2.1 in aPBC, 3.4+/-1.3 in chronic hepatitis C, and 3.6+/-2.3 in cirrhosis secondary to CH-C; p < 0.05 for sPBC vs all others). Histological examination of these patients showed that all aPBC patients belonged to relatively early stage (stage I-II) and 7 of 8 sPBC patients belonged to late stage (stage III-IV). Thus, our results suggest that, mainly as a result of the decline of Th2, a predominance of Th1 may exist in advanced stage PBC. CONCLUSIONS: The present results demonstrated that a slight elevation of Th1 prevalence, as well as a significant decline of Th2 prevalence, was observed in peripheral blood of advanced stage PBC.

Adult↗
PubMed1999

Decreased expression of t-SNARE, syntaxin 1, and SNAP-25 in pancreatic beta-cells is involved in impaired insulin secretion from diabetic GK rat islets: restoration of decreased t-SNARE proteins improves impaired insulin secretion.

The physiological role of soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) proteins in insulin exocytosis has been reported in pancreatic beta-cells. To determine whether the beta-cells of GK rats, a nonobese rodent model of type 2 diabetes, exhibit abnormalities in their SNARE proteins, we studied the expression and function of target (t)-SNAREs, syntaxin 1A, and synaptosomal-associated protein of 25 kDa (SNAP-25) in GK rat islets. Although insulin release and insulin content of islets isolated from 12-week-old GK rats were reduced, the proinsulin biosynthetic rate was about twofold higher than that in control rat islets, and no change in the preproinsulin mRNA level was observed. Pulse-chase experiments suggested the increased degradation of insulin in GK rat islets. Immunoblot analysis revealed that protein levels of syntaxin 1A and SNAP-25 in GK rat islets decreased to approximately 60% of the levels in control rat islets. We then examined whether the restoration of the decreased expression of t-SNAREs to the normal level in GK rat islets affected insulin secretion. Restoration was achieved by the overexpression of syntaxin 1A and SNAP-25 via the recombinant adenovirus-mediated gene transduction system, which recovered levels of these proteins to almost control levels. Glucose-stimulated insulin release from AdexlCA syntaxin 1A and Adex1CA SNAP-25-infected GK rat islets increased up to approximately 135 and 200%, respectively, of those from uninfected GK rat islets, although no difference in basal (2.2 mmol/l glucose) insulin release was evident between them. We conclude that decreased expression of t-SNAREs in GK rat islets is in part the defect responsible for impaired insulin secretion.

Animals↗
PubMed1998

Quantitative light microscopic study on the heterogeneity in the superficial pineal gland of the rat.

BACKGROUND: The previous results regarding regional and day-night differences in pinealocyte size in rats are conflicting. The relationships between these differences and the vascularity and sympathetic innervation have scarcely been investigated. METHODS: Wistar-King rats, kept under light/dark 12:12, were killed at midday or midnight in October. The nuclear density of pinealocytes in the superficial pineal was measured on the dorsoperipheral, dorsocentral, ventroperipheral, and ventrocentral regions at distal, middle, and proximal levels at daytime and nighttime. The total area of blood vessels per unit area at daytime and nighttime and total length of tyrosine hydroxylase (TH)-immunoreactive fibers per unit area at daytime were determined on the same regions at the same levels. RESULTS: Pinealocyte size was larger toward the distal levels and in the periphery than in the center at any level. The area of blood vessels and length of TH fibers were also larger toward the distal levels; the former in the ventral region and the latter in the dorsal and ventral regions were larger in the periphery than in the center. Ventral pinealocytes, but not dorsal ones, showed day-night changes in size. Prominent day-night rhythms in area of blood vessels occurred in the ventral region, where TH fibers were more abundant than in the dorsal region. CONCLUSIONS: Pinealocyte size shows the distal to proximal and peripheral to central gradients, which may be related to the differential distribution of blood vessels and sympathetic fibers. Since pinealocytes and blood vessels, showing prominent day-night changes in size, are localized in the more richly innervated regions, sympathetic fibers may play an important role in controlling these rhythms.

Analysis of Variance↗
PubMed1998

Indoleamine metabolism in the pineal gland of the Chinese hamster, Cricetulus griseus.

Day- and nighttime contents of pineal melatonin and other indoleamines were measured in the Chinese hamster, Cricetulus griseus. The hamsters were inbred in our colony and kept in LD 14:10. Absolute levels of pineal melatonin and N-acetylserotonin contents were extremely low, but showed a significant circadian rhythm with a minor peak during the light period. Pineal hydroxytryptophan and serotonin (5HT) contents were also found to be higher in the light period. The activity of N-acetyltransferase in the pineal was higher in the light period than in the dark period, whereas there was no difference in hydroxyindole-O-methyltransferase activity between the light and dark periods. The uptake level of tryptophan into the pineal gland was higher in the light period than in the dark period. These results suggest that the 5HT synthesis pathway and/or tryptophan uptake may be involved in forming the circadian rhythm of 5HT content in the Chinese hamster pineal gland.

5-Hydroxytryptophan↗
PubMed1998

The increase of memory T cell subsets in children with idiopathic nephrotic syndrome.

Two-color and three-color flow cytometry was carried out to determine whether the memory T cells (CD45RO+ T cells) play a major role in lymphocyte dysfunction of 26 children with idiopathic nephrotic syndrome (INS). The INS patients were divided into three groups: (1) 10 patients who were not receiving glucocorticoid hormone (GCH) and were suffering from acute nephrotic state were referred to as N1; (2) 8 patients who were in remission maintained by GCH therapy alone were referred to as N2; (3) 8 patients who were free of GCH therapy for at least 4 months were referred to as N3. Group N1 demonstrated a significant increase in the percentage of CD45RO+CD4+ T cells and CD45RO+CD8+ T cells (p < 0.05) compared with 11 controls, and these subsets were noted to have a tendency to decrease to control levels in groups N2 and N3. Furthermore, interleukin-2 receptor-alpha expressed subsets in CD45RO+CD4+ T cells (CD45RO+CD4+CD25+ T cells) were also increased only in group N1 (p < 0.02). A similar tendency of absolute counts was observed in these subsets. These results suggest that activated memory T cells reflect lymphocyte dysfunction at initial onset or relapse in INS children.

Antibodies, Monoclonal↗
PubMed1998

Health effects of indoor fluoride pollution from coal burning in China.

The combustion of high fluoride-content coal as an energy resource for heating, cooking, and food drying is a major exhaust emission source of suspended particulate matter and fluoride. High concentrations of these pollutants have been observed in indoor air of coal-burning families in some rural areas in China. Because airborne fluoride has serious toxicological properties, fluoride pollution in indoor air and the prevalence of fluorosis have been analyzed in a fluorosis area and a healthy nonfluorosis area in China and in a rural area in Japan. For human health, fluoride in indoor air has not only been directly inhaled by residents but also has been absorbed in stored food such as corn, chilies, and potatoes. In the fluorosis area in China, concentrations of urinary fluoride in the residents have been much higher than in the nonfluorosis area in China and in the rural area in Japan. In the fluorosis area, almost all elementary and junior high school students 10-15 years of age had dental fluorosis. Osteosclerosis in the skeletal fluorosis patients was very serious. Urinary deoxypyridinoline in rural residents in China was much higher than in rural residents in Japan. Data suggest that bone resorption was extremely stimulated in the residents in China and that fluoride may stimulate both bone resorption and bone formation. Because indoor fluoride from combustion of coal is easily absorbed in stored food and because food consumption is a main source of fluoride exposure, it is necessary to reduce airborne fluoride and food contamination to prevent serious fluorosis in China.

Adolescent↗
PubMed1997

Propiverine hydrochloride, an anti-pollakiuric agent, inhibits the activity of actomyosin ATPase from the urinary bladder.

The present study was performed to investigate the effects of propiverine hydrochloride (1-methyl-4-piperidyl diphenylpropoxyacetate hydrochloride, P-4), a novel anti-pollakiuric agent, on the contractile proteins of smooth muscle. P-4 (30-300 microM) inhibited the activity of native actomyosin adenosine triphosphatase (ATPase) that had been freshly purified from canine urinary bladder, and calmodulin at 10 microM overcame this inhibition. P-4 also inhibited myosin light chain kinase from smooth muscle in a dose-dependent manner. However, at 300 microM, P-4 was unable to inhibit by 50% the activity of trypsin-treated myosin light chain kinase, which was independent of Ca2+/calmodulin. 1 mol of calmodulin bound 4 to 5 mol of [14C]P-4 in a Ca2+-dependent manner with a K(d) of 77.4 microM. These results indicate that calmodulin is one of the intracellular target molecules for P-4 and that inhibition of the action of calmodulin by P-4 might cause the inhibition of actomyosin ATPase activity, with subsequent relaxation of the smooth muscle of the urinary bladder.

Animals↗
PubMed1997

Differentiation and morphogenesis in pellet cultures of developing rat retinal cells.

We previously developed a reaggregate cell culture system (pellet cultures) in which retinal neuroepithelial cells proliferate and give rise to rod photoreceptor cells (rods) in vitro (Watanabe and Raff, 1990, Neuron 4:461-467). In the present study, we analyzed cell differentiation and morphogenesis in pellet cultures by using both cell-type-specific markers with immunofluorescence and electron microscopy. We demonstrated that, in addition to rods, the other major retinal cell types, including amacrine cells, bipolar cells, Müller cells, and ganglion cells were all present in the pellets, where most were able to develop from dividing precursor cells in vitro. The different cell types in the pellets became organized into two distinct structures: dark rosettes and pale rosettes. The cellular composition of these structures indicated that the dark rosettes correspond to the outer nuclear layer and the pale rosettes to the inner nuclear layer of the normal retina. Ultrastructural studies have indicated that the thin layer of neuronal processes surrounding the dark rosettes correspond to the outer plexiform layer, and the central region of the pale rosettes correspond to the inner plexiform layer of the normal retina. Other features of normal retinal development also occurred in the pellets, including programmed cell death and the formation of inner and outer rod cell segments and synapses. Thus, pellet cultures provide a convenient way to study different aspects of retinal development where one can control the size and the cellular composition of the initial reaggregate.

Animals↗
PubMed1997

QM is a novel zinc-binding transcription regulatory protein: its binding to c-Jun is regulated by zinc ions and phosphorylation by protein kinase C.

A novel method was developed for cloning of zinc-binding proteins. We used 65Zn2+ as a probe to screen a human lung cDNA library, and isolated QM using this approach. QM appears to be a negative regulator of c-Jun that acts by binding to the leucine zipper region of c-Jun. We demonstrated that QM bound zinc ions and that such binding was necessary for the interaction of QM with c-Jun. We also showed that protein kinase C introduced about 1 mol of phosphate into 1 mol of QM. The binding of QM to c-Jun was decreased by 60% when QM had been phosphorylated. These results suggest that QM is a novel zinc-binding transcription regulatory protein and that interaction between QM and c-Jun is regulated by zinc ions and phosphorylation.

Binding Sites↗
PubMed1997

Low level c-myc gene amplification in gastric cancer detected by dual color fluorescence in situ hybridization analysis.

BACKGROUND AND OBJECTIVES: By using the dual color fluorescence in situ hybridization analysis, the amplification of c-myc gene can be detected in the tumor tissue samples obtained from patients with gastric cancer, and the relationship between the molecular cytogenetic change and the clinical stage or histological type may be clarified. METHOD: The tumor tissue samples were obtained from 21 patients with gastric cancer. Simultaneous detection of signals from the chromosome 8 centromere and c-myc gene in each cell after hybridization with appropriate probes was carried out on 50-200 tumor cells in each case. RESULTS: Chromosome 8 polysomy was found in 10 patients. The average centromere 8 copy number was significantly higher in differentiated (2.7) than in undifferentiated (2.3) types of gastric cancer. However, there was no significant difference in occurrence of polysomy 8 between early and advanced cancer. The relative gain (1.1-1.9) of c-myc copy number was found in all 21 cases. There was no significant difference in the fraction of cells with c-myc gene amplification between early (pT1) and advanced (pT2-4) carcinomas. CONCLUSION: We conclude that the present dual color fluorescence in situ hybridization of gastric cancer may be useful in the evaluation of low level c-myc gene amplification, which is difficult to detect by Southern blotting, and may be applicable to the diagnosis of early gastric cancer.

Adult↗
PubMed1997

Non-functional role of syntaxin 2 in insulin exocytosis by pancreatic beta cells.

This study was designed in order to examine the expression and functional role of syntaxin 2/epimorphin in pancreatic beta cells. Northern blot analysis revealed that syntaxin 2 mRNA was able to be detected in mouse beta TC3 cells, but not in isolated mouse islets. In agreement with this result, immunoblot analysis detected an appreciable amount of syntaxin 2 protein in beta TC3 cells, but not in mouse islets. Immunohistochemistry of the mouse pancreas demonstrated that syntaxin 2 was little evident in islet cells of Langerhans, and somewhat predominant in exocrine tissues. In order to examine whether syntaxin 2 is anchored to cell surfaces in beta TC3 cells, living cells were incubated with a monoclonal antibody against syntaxin 2 (MC-1). The antibody bound to their surfaces, indicating that syntaxin 2 was localized on cell surfaces. The addition of MC-1 to the culture medium of beta TC3 cells did not affect insulin release under the presence or absence of 11 mM glucose, indicating that syntaxin 2 is not associated with insulin exocytosis. Thus, the expression of syntaxin 2 in islets of Langerhans is very low and the function of this protein is probably unrelated to the insulin exocytosis pathway.

Animals↗
PubMed1997

Effect of an endothelin-1 antagonist, BQ-485, on cerebral oxygen metabolism after complete global cerebral ischemia in dogs.

Endothelin-1 (ET-1) plays an important role in the physiologic or pathophysiologic regulation of cerebral circulation. To evaluate the effects of the newly synthesized ETA receptor-selective antagonist, BQ-485 (N-perhydroazepin-l-ylcarbonyl-Leu-D-Trp-D-Trp-OH), on the cerebral metabolism of oxygen during the delayed cerebral hypoperfusion that follows global cerebral ischemia, we occluded the ascending aorta and caval veins of 10 beagle dogs for 12.5 min. The animals were randomized into two groups. BQ-485 was given directly into the carotid artery at 0.03 mg/kg per min for 30 min, starting 15 min after reperfusion in the treatment group (n = 5). Isotonic saline was infused in the control group (n = 5). A fiberoptic catheter was inserted into the superior sagittal sinus to monitor its oxygen saturation (SssO2) continuously. Arterial O2 content (CaO2), and sagittal sinus O2 content (CssO2) were monitored before and at 0.5, 1, 2, 4, 6 and 8 h after the ischemic insult. BQ-485 significantly prevented the expected decrease in SssO2 and increase in the cerebral O2 utilization coefficient at 4, 6 and 8 h after the ischemic insult (P < 0.05). Thus, BQ-485 ameliorated the mismatch between O2 supply and demand in the delayed hypoperfusion phase. We conclude that ET may be involved in the pathogenesis of delayed cerebral hypoperfusion after cardiac arrest.

Analysis of Variance↗
PubMed1997

[Quantitative evaluation of magnetization transfer ratio in irradiated breast with breast conservation therapy].

To assess the late effects of radiotherapy, magnetization transfer was evaluated in 2 patients with breast conservation treatment and in 4 patients without treatment. The magnetization transfer ratios (MTRs) were measured from a pair of images obtained by the conventional SPGR pulse sequence and the MT-prepared SPGR sequence on a 1.5-TMR system. The MTR values of irradiated breast were higher than those of non-irradiated breast. The difference in MTR between them was considered to represent tissue change due to irradiation. We showed that MTR is a useful parameter in estimating the late effects of radiotherapy.

Adipose Tissue↗
PubMed1996

Localization and ontogeny of GLUT3 expression in the rat retina.

This study investigates the presence, localization, and developmental expression of a neuron-specific facilitated-diffusion glucose transporter, GLUT3, in the rat retina so as to elucidate molecular mechanisms regulating glucose homeostasis in support of the visual function. Immunoblot analysis using anti-GLUT3 antibody (ALM3-C) revealed the presence of GLUT3 as a heterogeneously glycosylated protein with an average molecular weight of approximately 44 kDa. Although immunofluorescence staining showed it to be localized primarily in the inner and outer plexiform layers, some of the cell bodies in the inner nuclear layer also showed weak immunoreactivity. Immunoblot analysis of developing rat retinal tissues revealed the presence of the GLUT3 protein as early as embryonic day 15 (E15), and immunofluorescence staining revealed its expression in the inner plexiform layer near the time of birth and in the outer plexiform layer at postnatal day 14 (P14), i.e., when the eyes normally open and retinal activity commences. The protein's abundance remained at a relatively low level during the embryonic stages and up until the end of the first postnatal week (P7), though a transient increase was confirmed to occur at E18. From P13, however, the abundance steadily increased, rapidly reaching the adult level at P24. Based on these observations, we hypothesize that GLUT3 is expressed in some subsets of retinal neurons, being preferentially abundant in their neuronal processes, and that its ontogeny is closely associated with morphological and functional development of the retina. As such, this suggests that GLUT3 plays some important role(s) in the retina where glucose metabolism is essential.

Animals↗
PubMed1996

Simultaneous determination of serotonin, N-acetylserotonin and melatonin in the pineal gland of the juvenile golden hamster by high-performance liquid chromatography with electrochemical detection.

A simple and simultaneous determination of melatonin and its precursors, serotonin (5-HT) and N-acetylserotonin, was achieved by reversed-phase high-performance liquid chromatography with electrochemical detection. The addition of an ion-pairing agent, sodium 1-octanesulfonate, to the chromatographic mobile phase caused an increase of the retention time of 5-HT, and resulted in the successful simultaneous resolution of these three indoleamines. This method was used to quantitate these indoleamines in the pineal gland of juvenile golden hamsters.

Animals↗