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Biomedical subjects

S Shimada

Publications and source records attributed to S Shimada.

At least 163 records · Page 9Linked to original sources

Do repolarization abnormalities in hypertrophic cardiomyopathy represent impaired fatty acid utilization? An observation with QRST isointegral maps.

To identify the clinical significance of the isointegral body surface map of the QRST interval (QRST map) and the occurrence of repolarization abnormalities in patients with hypertrophic cardiomyopathy (HCM), the QRST map and signal-averaged electrocardiogram were evaluated in 50 patients with HCM, in 33 of whom the results were compared with nuclear images both for radioiodine-labeled fatty acid metabolism and for radiothallium perfusion. The QRST departure map was used to determine two parameters of difference between patient and control recordings: the subnormal area (the number of lead points at which the departure index values were negative and lay more than 2 SDs from the mean of the normal control group) and the subnormal minimum (the absolute value of the minimum in the departure map). Late potentials were detected in 6 (12%) of the 50 patients; they were observed in 3 of the 5 patients with dilated-phase HCM but in only 3 (7%) of the other 45 patients. The subnormal area and minimum values were lower in nonobstructive HCM than in dilated-phase HCM. Of the 33 patients examined by myocardial imaging, 28 (33%) had a filling defect or decreased uptake, as shown on fatty acid metabolic images, and 10 of the 28 also showed abnormal myocardial perfusion images, while the 18 others showed normal perfusion images. These 28 patients showed significantly larger values of the subnormal area and minimum than patients with normal results in both image tests, regardless of whether or not myocardial perfusion imaging abnormalities were present. The localization of filling defects or of decreased uptake presented in fatty acid metabolic images corresponded to the position of the minimum on the QRST departure map. These results suggest that the QRST map is useful for detection of repolarization abnormalities in HCM and that these abnormalities are highly related to impaired fatty acid utilization of the myocardium.

Adolescent↗

Expression of c-fos and c-jun mRNA following transient retinal ischemia: an approach using ligation of the retinal central artery in the rat.

The expression of the proto-oncogenes c-fos and c-jun was examined by in situ hybridization at various timepoints following transient retinal ischemia by means of ligation of the retinal central artery in the rat. Ischemia of 90-minute duration resulted in the degeneration of neurons in both the ganglion cell layer and the inner nuclear layer at 48 hours after reperfusion. The expression of c-fos and c-jun messenger RNA throughout the entire inner nuclear layer was transiently coinduced following 90-minute retinal ischemia with a peak at 1 hour after reperfusion. This expression was also found in the ganglion cell layer at 3 hours after reperfusion. Weak signals for c-fos and c-jun mRNA were observed at 24 hours after reperfusion and returned to near control levels by 48 hours. c-jun protein expression was detected in the ganglion cell layer, the middle of the inner nuclear layer, and optic nerve head at 3 hours, but not 1 hour, after lethal ischemia/reperfusion; however, c-fos protein expression was not detected after reperfusion. Whereas no neuronal degenerative changes were found at 7 days after 30-minute ischemic retina, c-fos and c-jun messenger RNA were also induced at 1 hour postreperfusion. To our knowledge, this study is the first report to show expression patterns of immediate-early genes after retinal ischemia/reperfusion. These results suggest that changes in expression of c-fos and c-jun after transient retinal ischemia are similar to those after transient brain ischemia, and the selective occlusion of the central retinal artery will provide a useful model for studying ischemic neuronal degeneration in vivo in the rat retina.

Animals↗

Regional distribution of GABA transporter 1 (GAT1) mRNA in the rat brain: comparison with glutamic acid decarboxylase67 (GAD67) mRNA localization.

The mRNA expression of GABA transporter 1 (GAT1) was investigated in the rat brain by in situ hybridization histochemistry using an oligonucleotide probe specific to the mRNA. The pattern of GABA transporter 1 mRNA expression was well coincident with that of GABAergic terminals detected by using glutamic acid decarboxylase (GAD) as a marker. In addition, we compared the GAT1 mRNA expression with that of glutamic acid decarboxylase67 (GAD67) mRNA positive neurons. Although the expression patterns of both mRNAs were similar in most nuclei, the number of GABA transporter 1 mRNA positive cells were higher than that of GAD67 mRNA positive cells in some nuclei, such as the inferior colliculus, cerebellar nuclei and cerebral cortex. Furthermore the subthalamic nucleus and inferior olive nucleus, which lacked GAD67 mRNA expression, showed intense GABA transporter 1 mRNA expression. These data suggest that GABA transporter 1 mRNA is expressed not only in GABAergic neurons but also in non-GABAergic neurons and/or glial cells which are involved in GABAergic neurotransmission.

Animals↗

The differential osmoregulation and localization of taurine transporter mRNA and Na+/myo-inositol cotransporter mRNA in rat eyes.

We studied the cellular localization and osmotic regulation of taurine transporter (TauT) mRNA in the rat eyes using in situ hybridization. TauT mRNA signals were expressed in the ciliary body, and the outer part of the inner nuclear layer (INL), the outer nuclear layer (ONL) and the inner segment (IS) of the adult rat retina. Chronic hypernatrema, induced by gavaging with 1 ml/100 g body weight of 5% NaCl every other day for 7 days, markedly increased in TauT mRNA in the retina compared with control rats. However, there was little change in TauT mRNA in the eyes in acute hypernatremic state that is induced by single injection of high concentration of NaCl. On the contrary, acute hypernatremic rats displayed markedly elevated Na+/myo-inositol cotransporter (SMIT) mRNA in the retina and the iris-ciliary body and the lens epithelium. Under chronic hypernatremic conditions, there was no significant increase in SMIT mRNA in rat eyes. These findings suggest that TauT mRNA is osmotically regulated in vivo to protect retinal neuronal function, especially against chronic hypernatremic conditions, in contrast to rapid up-regulation of SMIT mRNA in acute hypernatremic rats.

Animals↗

Differential expression patterns of GABA transporters (GAT1-3) in the rat olfactory bulb.

The localization of GABA transporters 1-3 (GAT1-3) was investigated in the rat olfactory bulb by using in situ hybridization and immunohistochemistry. In the glomerular and the internal granular layers, GAT1 mRNA was expressed in most of periglomerular and granule cells, which are known to be GABAergic. In addition, we compared GAT1 mRNA expression with that of glutamic acid decarboxylase67 (GAD67) mRNA. The expressions were very similar in these two layers, indicating that GAT1 mRNA is mainly expressed in GABAergic neurons. However, in the external plexiform and the olfactory nerve layers, we observed more GAT1 mRNA-positive cells than GAD67 ones, suggesting that GAT1 mRNA is also expressed in non-GABAergic neurons and in glial cells. GAT3 mRNA expression was observed in small glial-like cells which might be involved in GABAergic neurotransmission throughout the olfactory bulb. This was confirmed by double-immunostaining studies which showed the expression of both GAT3 and glial fibrillary acidic protein (GFAP) mRNAs in astrocytes. Moreover, GAT2 mRNA was expressed only in the ependyma and arachnoid. These findings suggest that the expression patterns of GABA transporters differ with the type of cells in the rat olfactory bulb where GAT1 and GAT3 may play an imporatant role in GABA-mediated transmission, such as lateral inhibition.

Animals↗

Induction of Na+/myo-inositol co-transporter mRNA after rat cryogenic injury.

Myo-inositol is one of the major organic osmolytes in the brain. It is stored in the cells by the Na+/myo-inositol co-transporter (SMIT) which is regulated by extracellular osmolality. First, in order to confirm that local change of the osmolality induces alteration of the SMIT mRNA in brain, we examined change of SMIT mRNA of the animals with hypertonic NaCl application to the cortex. Application of hypertonic NaCl up-regulated the SMIT mRNA expression widely surrounding the application site. We next investigated the role of SMIT in brain during vasogenic edema, we examined expression of SMIT mRNA in the rat brain after cryogenic injury. The expression of SMIT mRNA was markedly increased 12 h after surgery and the induction of the mRNA extended to the entire cortex of the affected side. Up-regulated expression was found predominantly in the neurons in remote areas. The induction of SMIT mRNA was found until the 3rd day after surgery. These findings suggest that osmotic stress may spread over a wide area in the cortex in case of vasogenic edema produced by cryogenic injury and that the cells respond to this stress by increasing SMIT expression.

Animals↗

Developmental regulation of Na+ / myo-inositol cotransporter gene expression.

myo-Inositol plays a role in many important aspects of cellular regulation including membrane structure, signal transduction and osmoregulation. It is taken up into the cells by the Na+ / myo-inositol cotransporter (SMIT). We investigated developmental changes in the expression of SMIT mRNA and protein in the rat. In the fetal rat brain, SMIT mRNA was abundantly and diffusely expressed throughout the whole brain and the spinal cord. Positive signals were expressed in neuronal and non-neuronal cells in these regions. SMIT is gradually down-regulated nearer birth, but intense signals were still detected in the brain at postnatal day one. In the adult rat brain, very weak hybridization signals were detected throughout whole brain except for the choroid plexus where SMIT mRNA expression remained high. In contrast, the pattern of developmental regulation of SMIT gene expression in the kidney was opposite to that seen in the brain. Signals in the kidney were very weak during embryonic stages, whereas SMIT expression increased significantly after birth. These results suggest that myo-inositol and its transporter play an important role in the CNS developmental stage.

Aging↗

Effects of partial nephrectomy on the expression of osmolyte transporters.

Na+/myo-inositol cotransporter (SMIT) and Na+/Cl-/betaine-gamma-amino-n-butyric acid transporter (BGT-1) are the major osmolyte transporters that are regulated by extracellular osmolarity. We have recently shown localization and rapid regulation of the mRNAs for these transporters in rat kidney. In the present study, we examined the expression of SMIT and BGT-1 in partial nephrectomized rats in order to assess the change in local osmolarity following reduction of renal mass. Four weeks after 5/6 nephrectomy (NX), the rats were compared to sham-operated control animals (CONT). Northern analysis using RNA of whole kidney indicated that there were little differences in the levels of SMIT and BGT-1 mRNAs between the two groups. In situ hybridization revealed that signals for both transporter mRNAs were markedly reduced in the inner medulla of the remnant kidney. In contrast, these signals in the outer medulla increased following nephrectomy. SMIT signals in the cortex increased as well. Grain density, determined by counting grain number per cell, revealed that the signals in the inner medullary collecting ducts were markedly reduced whereas those in the thick ascending limbs of Henle (TAL) as well as macula densa cells were significantly increased. The signals in the TAL and macula densa were reduced by furosemide administration. The increased expression in NX rats may reflect the increased NaCl transport and high local osmolarity in this segment.

Animals↗

A step-wise expansion of intestinal intraepithelial T lymphocytes in association with microbial colonization is defined by sensitivity to cyclosporin A.

Murine intestinal intraepithelial lymphocytes (IELs) consist of T cells bearing alpha beta-antigen receptor (alpha beta-IELs) and those bearing gamma delta-IELs). Although gamma delta-IELs outnumber alpha beta-IELs in germ-free (GF) mice, oral inoculation of fecal suspension from conventional (CV) mice into GF mice induced the increase in number of alpha beta-IELs, leaving the number of gamma delta-IELs unchanged, and the number of alpha beta-IELs reached the level of CV mice by 3 weeks after conventionalization. Expansion of alpha beta-IELs and increase in their CD44+ subset in conventionalized mice were not affected until 2 weeks after beginning of daily injection of cyclosporin A (CsA). However, further expansion of alpha beta-IELs during 2-3 weeks after conventionalization was blocked by injection of CsA. Although the relative constitution of CD4- 8-, CD4+ 8-, CD4- 8 alpha alpha+, CD4- 8 alpha beta+ and CD4+ 8+ subsets among alpha beta-IELs was comparable between control and CsA-treated groups, CsA injection resulted in the decrease in ratio of high-density fraction cells to low density fraction cells in IELs. CsA completely abrogated the expansion of T cells in peripheral lymph nodes stimulated by alloantigens in vivo, and proliferation of IELs from GF mice induced by immobilized anti-alpha beta-T-cell receptor (TCR) monoclonal antibodies (mAb) in vitro was also eliminated by CsA. These results indicate that microbial colonization-induced expansion of alpha beta-IELs is subdivided into two steps: the early phase of expansion takes place via TCR-non-mediated pathway and the late phase of expansion requires TCR-mediated signal transduction.

Animals↗

Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma.

To assess intrahepatic metastasis (IM) and multicentric occurrence (MO) after initial treatment of small hepatocellular carcinomas (HCC) < or = 2 cm in diameter, we performed clinical and pathological studies in 112 patients who underwent percutaneous ethanol injection therapy (PEIT) or hepatic resection for HCC from January 1985 to December 1994. Patients with intrahepatic recurrences were classified into two groups based on the type of recurrence: the IM group (n = 29, 50.9%) and the MO group (n = 28, 49.1%). Overall recurrence rates after initial treatment were 23.7% at 1 year, 64.5% at 3 years, and 76.1% at 5 years. In patients with IM, the majority of intrahepatic recurrences were observed within 3 years of initial treatment and the primary HCC lesions were closely related to the degree of tumor cell differentiation. Alternatively, intrahepatic recurrences occurred throughout the follow-up period in patients with MO, and the evidence of underlying liver disease (anti-HCV [antibody to hepatitis C virus] positive) and elevated serum alfa-fetoprotein (AFP) concentrations were closely associated with intrahepatic recurrence. Prognoses following additional treatment in MO group patients were superior to those in IM group patients. These results suggest that differentiation between IM and MO in patients with HCC is important for understanding the development and biological behavior of the tumor. That is, the early detection of intrahepatic recurrence and the institution of appropriate additional therapy (PEIT or hepatic resection) may prolong survival in patients with MO.

Adult↗

Clinical efficacy of lactulose in cirrhotic patients with and without subclinical hepatic encephalopathy.

Seventy-five cirrhotic patients with hyperammonemia in the past or at the time of the study were randomly divided into two groups (treated with lactulose or nontreated) in 14 hospitals in Japan. Thirty-six cirrhotic patients were diagnosed as having subclinical hepatic encephalopathy (SHE), and 39 were diagnosed as non-SHE. SHE was diagnosed when the results of all three of the quantitative psychometric tests used (number connection test, and symbol digit and block design tests of the Wechsler adult intelligence scale [revised]) were abnormal as compared with age-matched normal values. The mean number of abnormal psychometric test results and the prevalence of SHE were used for a quantitative evaluation of the efficacy of the lactulose treatment. Twenty-two of the SHE patients were treated with lactulose (45 mL/d) for 8 weeks, and the other 14 SHE patients did not receive lactulose. In the SHE patients administered lactulose, the results of the quantitative psychometric evaluation were significantly improved at 4 and 8 weeks after the beginning of the lactulose administration. The SHE had disappeared in 10 (50%) of the 20 treated patients at week 8, but it persisted in 11 (85%) of the untreated 13 patients. We concluded that lactulose treatment in cirrhotic patients with SHE is effective with respect to psychometric tests.

Administration, Oral↗

Mechanisms producing color change in flat early gastric cancers.

BACKGROUND AND STUDY AIMS: Although highly refined endoscopes have made it possible to detect not only early gastric cancers with morphological changes, but also flat-type tumors (type IIb) on the basis of the color changes observed in them, the factors responsible for color changes in type IIb carcinomas have not been fully elucidated. The aim of this study was to analyze the potential mechanisms underlying these color changes. PATIENTS AND METHODS: Thirteen type IIb cancers were selected from a total of 589 resected gastric cancers detected preoperatively using endoscopic examination. All of the tumors showed color changes alone, without surface changes, and the color changes included redness, discoloration, and spotty bleeding. Detailed histological examination of the resected stomachs revealed twelve more II b lesions that had not been identified at endoscopy. The endoscopic appearance of the IIb cancers were correlated with the degree of tumor differentiation, the extent of wall infiltration, and the number of capillaries. RESULTS: In cases that were detectable by endoscopy, the endoscopic color appearance correlated significantly with both tumor size (P < 0.02) and with the extent of mucosal cancer infiltration (P < 0.02). Histological examination of the IIb lesions revealed that redness and discoloration were significantly more frequent in the differentiated and undifferentiated cancer types, respectively (P < 0.01). There was a significant difference in the number of capillaries between type IIb carcinoma and the adjacent normal mucosa, but not between cancers. The numbers for differences in redness and discoloration were 7.0 +/- 5.6 and -14.0 +/- 8.8, respectively. CONCLUSIONS: These results suggest that the main factor underlying color change in type IIb early gastric cancers may be the number of capillaries in the lesions, in comparison with the adjacent mucosa. Whether the lesion is visible on endoscopy, however, depends more on its size than on the number of capillaries.

Adult↗

Trends in neonatal exchange transfusions at Yodogawa Christian Hospital.

A review was conducted to determine the trends in exchange transfusion (ET) of newborn infants at the Yodogawa Christian Hospital during the past 18 years. At that hospital in 1957, the first ET was performed on a term infant with severe hemolytic jaundice caused by rhesus factor (Rh) incompatibility. By 1989, ET had been performed in more than 1400 newborn infants. These cases of newborns who had had ET were retrospectively reviewed, with a focus on every 3 year period from 1974 to 1992. The total number of infants requiring ET noticeably decreased from 68 cases (14.0% of total admissions) in 1974 to 19 cases (6.1% of total admissions) in 1992. (chi 2, P < 0.001) There were three major significant changes in ET during those years. The first was a change in the subjects for ET. The incidence of ET for term infants showed a marked decrease, while the incidence of ET for preterm infants, especially for very low birthweight (VLBW) infants (< 1500 g), noticeably increased. The second was a change in indications for ET. There was a marked decrease in the need for ET as a result of hyperbilirubinemia, while the incidence of ET because of other etiologies, such as septicemia and/or disseminated intravascular coagulopathy, noticeably increased. The third was a change in the technical methods of ET. Now at the Yodogawa Christian Hospital, 100% of the infants are given ET with an automated peripheral two-site method, instead of the Diamond method. Although ET might still be a useful treatment for severe hyperbilirubinemia and other acute problems, the total number of ET noticeably decreased in accord with a decrease in the number of severe hyperbilirubinemia in term newborns. On the other hand, the incidence of ET in preterm infants increased relatively, accompanied by an increase in the survival of VLBW infants. The automated two-site method is the preferred technique for ET at the Yodogawa Christian Hospital, rather than the Diamond method. Further changes in ET might occur in accord with new alternative measures in future.

Christianity↗

Inactivation of a particle beta-glucan by proteins in plasma and serum.

(1-->3)-beta-D-Glucans remained in the liver and spleen for long time, i.e. more than a month, without major structural changes/because there is no specific metabolic pathway for it in the body. However, biological activities, such as priming activity to LPS, triggered TNF-alpha synthesis, and antitumor activity was reduced more quickly. In this paper, we demonstrated the contribution of protein binding in inactivating beta-glucans. A particle beta-glucan preparation, zymosan, was treated with serum or plasma at 37 degrees C and their various biological activities were compared with zymosan alone. Such biological activities as antitumor activity, TNF-production, IL-6 production, complement activation and vascular permeability were significantly decreased by serum or plasma treatment. These results strongly suggested that the binding of serum or plasma protein(s) to beta-glucans would be a key step in inactivating a particle beta-glucan in the body.

Animals↗

Immunohistochemical study of extracellular matrices and elastic fibers in a human sternoclavicular joint.

In this study, we clarified the distribution of elastic and oxytalan fibers in a human sternoclavicular joint (SCJ) using a color image system and in extracellular matrices using immunoperoxidase staining. Fine elastic fibers (EFs) were scattered in the fibrous layer of the sternoclavicular disk. This articular disk was composed of a collagenous bundle on the sternum side of the articular disk in the SCJ and cellular components including connective tissue on the clavicular side of the articular disk. The thickness of the disk gradually increased from the inferior to superior portion. Collagen fibers type I, III and V and other extracellular matrices (ECMs) were detected in the hypertrophic zone in the clavicular and sternum side of the SCJ and in the connective tissue of the articulatio condylar. On the cervical surface of the articular disk, cellular activity was higher than on the sternum surface.

Adult↗