Search PubMed⌕ Search

Biomedical subjects

H Matsubara

Publications and source records attributed to H Matsubara.

At least 127 records · Page 7Linked to original sources
PubMed1998

Effects of short duration morning bright light in healthy elderly. II: sleep and motor activity.

Subjective sleep feelings and motor activity were measured in seven healthy elderly subjects for 6 days. The subjects were exposed to bright light (6000 lux) for 30 min in the morning or instructed to sit in front of a desktop lighting device without light. The average level of motor activity during the night was significantly decreased in the bright light condition, compared with the controlled condition. However, daytime motor activity did not show significant differences between the two conditions. From these findings, even a short duration of morning bright light is effective in maintaining sleep without changing daytime activity.

Activity Cycles↗
PubMed1998

Dispersion of regional wall motion abnormality in patients with long QT syndrome.

OBJECTIVE: To examine the left ventricular regional wall motion abnormality and to evaluate dispersion of this abnormality in patients with long QT syndrome. DESIGN: Left ventricular short axis images at basal and middle levels were recorded on videotape and digitised to reconstruct digitised M mode echocardiograms, from which left ventricular wall thickness curves were obtained. The wall thickening time (ThT) was defined as the period in which the instantaneous wall thickness exceeded 90% of the maximum wall thickness. ThT was measured at three segments in each of the septal and free wall sides of the left ventricle, a total of 12 segments. To examine the mechanical dispersion of the left ventricle, the difference between the maximum and minimum ThT of 12 segments in each subject was obtained. PATIENTS: Eight patients with congenital long QT syndrome (averaged QTc interval (SD) 509 (27) ms1/2) and 10 control subjects (QTc interval 397 (26) ms1/2) were examined. RESULTS: The averaged ThT values of the 12 segments pooled form all subjects were correlated with the QT intervals (r = 0.72, p < 0.005). Thus the averaged ThT in the long QT syndrome patients was longer than in the control subjects (p < 0.005). The segmental variation of ThT in the patients was greater than in the control subjects (p < 0.001). The dispersion of ThT in the patients was therefore larger than in control subjects (p < 0.005). However, the pattern of ThT variation in the patients varied according to the individual subject. CONCLUSIONS: There is not only electrical but also mechanical dispersion in the left ventricle of long QT syndrome patients. Regional assessment of ventricular wall motion may allow quantification of the spatial variation of wall motion abnormality.

Adolescent↗
PubMed1998

Tissue-specific expression of human angiotensin II AT1 and AT2 receptors and cellular localization of subtype mRNAs in adult human renal cortex using in situ hybridization.

All studies analyzing the localization of angiotensin II (Ang II) receptors in the human kidney have been performed at the protein level using 125I-Ang II as a probe. In this study, cellular localizations of Ang II type l (AT1-R) and type 2 (AT2-R) receptor mRNAs in the adult human renal cortex were examined for the first time using in situ hybridization, and their expression patterns determined by RNase protection assay were compared with those in other human tissues. In the human renal cortex obtained from tumor-free portions in renal cell carcinoma, AT1-R mRNA levels were about 8- to 10-fold higher than AT2-R mRNA levels. Human liver and aorta predominantly expressed AT1-R mRNA, while human right atrium contained both AT1-R and AT2-R mRNAs. Ligand-binding assays revealed that the total Ang II receptor number in the human renal cortex was 16.0 +/- 3.3 fmol/mg protein, similar to that in liver (17.7 +/- 5. 8) but significantly higher than in right atrium (11.6 +/- 3.2) and aorta (5.6 +/- 2.7). Relative distribution ratios of AT1-R and AT2-R numbers in the renal cortex and right atrium were 82/17 and 56/42%, respectively. In situ hybridization study indicated that strongest AT1-R mRNA signals were located in interlobular arteries and tubulointerstitial fibrous regions surrounding interlobular arteries and glomeruli, followed in decreasing order by glomeruli and cortical tubules. Expression of AT2-R mRNA was highly localized in interlobular arteries. Cells present in tubulointerstitial regions were positive for vimentin and collagen type 1, indicating that the majority of the cells present in the regions are fibroblasts. Presence of strong AT1-R mRNA signals in the tubulointerstitial fibrous regions surrounding arteries and glomeruli and the expression of AT2-R mRNA in the interlobular artery were the first evidence, suggesting a pharmacological framework for the differential effects of Ang II receptor subtype mediated renal function in the adult human kidney.

Adult↗
PubMed1998

Role of calcium-sensitive tyrosine kinase Pyk2/CAKbeta/RAFTK in angiotensin II induced Ras/ERK signaling.

In cardiac fibroblasts, angiotensin II (Ang II) induced a rapid increase in extracellular signal regulated kinase (ERK) activity in a pertussis toxin insensitive manner. This ERK activation was abolished by the Gq-associated phospholipase C inhibitor U73122 but was insensitive to protein kinase C (PKC) inhibitors or PKC downregulation by phorbol ester. Intracellular Ca2+ chelation by BAPTA-AM or TMB-8 abolished Ang II induced ERK activation, whereas treatment with EGTA or nifedipine did not affect it. Ca2+ ionophore A23187 also induced a rapid increase in ERK activity to an extent similar to that of Ang II stimulation. Calmodulin inhibitors (W7 and calmidazolium) and tyrosine kinase inhibitors (genistein and ST638) completely blocked ERK activation by Ang II and A23187. Both Ang II and A23187 caused a rapid increase in the binding of GTP to p21(Ras), which was nearly abolished by genistein and calmidazolium. Transfection with the dominant negative mutant of Ras and the Ras inhibitor manumycin completely inhibited Ang II induced ERK activation. It was also found for the first time that cardiac fibroblasts abundantly expressed Ca2+-sensitive tyrosine kinase Pyk2/CAKbeta/RAFTK and that Ang II markedly induced its activation in a Ca2+/calmodulin-sensitive manner. Overexpression of the dominant negative mutant of Pyk2 significantly attenuated Ang II or A23187-induced ERK activities (36% and 38% inhibition compared with that in mock-transfected cells, respectively) and ERK tyrosine phosphorylation levels, as well as an increase in the binding of GTP to p21(Ras). These findings demonstrate that in cardiac fibroblasts, Ang II induced Ras/ERK activation is dominantly regulated by Gq-coupled Ca2+/calmodulin signaling and that Pyk2 plays an important role in the signal transmission for efficient activation of the Ang II induced Ras/ERK pathway.

Angiotensin II↗
PubMed1998

Induction of antitumor effect on human esophageal carcinoma cells by the retroviral expression of granulocyte macrophage-colony stimulating factor gene.

We have examined antitumor effect of human esophageal carcinoma cells (T.Tn) which were retrovirally transduced to express mouse granulocyte macrophage-colony stimulating factor (mGM-CSF) gene. Nude mice inoculated with T.Tn cells secreting mGM-CSF developed small tumors but the tumors regressed spontaneously, although the proliferation in vitro of transduced cells was not different from that of wild-type cells. In contrast, the tumor of T.Tn cells transduced with human GM-CSF grew as that of wild-type cells, since murine GM-CSF receptors do not bind to human GM-CSF. Histological examination of the regressing tumor of mGM-CSF-producing T.Tn cells revealed predominant infiltration of inflammatory cells including macrophages. In addition, local injection of mGM-CSF-producing T.Tn cells into the established wild-type tumors significantly induced the retardation of subsequent wild-type tumor growth, suggesting that T-cell independent local response plays a crucial role in destroying tumor cells.

Animals↗
PubMed1998

Antitumor response of genetically engineered IL-2 expression to human esophageal carcinoma cells in mature T cell-defective condition.

We examined whether antitumor effect could be produced by retrovirally expressed human interleukin-2 (hIL-2) gene in human esophageal cancer cells (T.Tn) using immunocompromised nude mice. Loss of tumorigenicity of hIL-2-producing T.Tn (T.Tn/hIL-2) cells inoculated subcutaneously was observed in contrast to continuous tumor growth of wild-type cells, although in vitro proliferation of T.Tn/hIL-2 cells remained the same as that of wild-type cells. The antitumor effect was also evidenced by the injection of T.Tn/hIL-2 cells into established tumors of wild-type cells. The injection significantly retarded the subsequent growth of wild-type tumors. Histological examination of regressing T.Tn/hIL-2 cells revealed necrotic areas and infiltration of several types of inflammatory cells. Treatment of nude mice with anti-asialoGM1 antibody did not influence the IL-2-mediated tumor rejection. Vaccination of nude mice with irradiated T.Tn/hIL-2 cells whose secretion of hIL-2 in amount was comparable to that of unirradiated cells did not develop protective immunity. Taken together, the antitumor effect achieved in nude mice by the inoculation of T.Tn/hIL-2 cells is mediated by non-T non-natural killer cells.

Animals↗
PubMed1998

[Vasopressin type 2 receptor mutations in congenital diabetes insipidus].

Congenital nephrogenic diabetes insipidus is a rare inherited disorder, which is characterized by the inability of the kidney to concentrate urine due to unresponsiveness to antiduretic hormone arginine vasopressin. Defects must be present somewhere in a vasopressin signal transduction pathway in kidney collecting duct. Recent genetic analysis demonstrated that mutations in vasopressin type 2 receptor and water channel aquaporin 2 are responsible for x-linked and autosomal recessive form, respectively. Expression studies of mutant proteins showed that most of the mutations cause severe functional defects, which are compatible with clinical phenotypes. These advances help understanding of molecular mechanism underlying this disease and therefore improve diagnostic and therapeutic approaches.

Animals↗
PubMed1998

[Pathophysiological function of angiotensin II AT1 and AT2 receptors and clinical application of AT1 antagonists].

Angiotensin II (Ang II) receptors are classified into two subtypes, type 1 (ATF-R) and type 2 (AT2-R) by development of non-peptidic antagonists. Classical Ang II function including vasopressor effect, cardiotropic action and aldosterone production is mainly mediated through AT1-R that present in cardiovascular system, adrenal glands and kidneys. AT1-R is abundantly expressed in whole bodies of fetus and its expression is abruptly decreased after birth, and in the adult AT2-R is expressed in brain nuclei, uterus, adrenal medullary glands and ovary. AT1-R and AT2-R are both G-protein coupled receptors and have 46% similarity in amino acid levels with seventh transmembrane conformation. Signal transduction pathway of AT1-R is mainly CA2+ and activation of protein kinase C, while that of AT2-R is still unknown. Clinical application of AT1-R antagonist started and this causes elevation of plasma Ang II levels, which selectively stimulates AT2-R. Thus, one should realize AT2-R-mediated effect in treatment with AT1-R antagonist. We have shown that AT2-R has anti-AT1-R action, such as inhibitory action against AT1-R-mediated positive chronotropic effect or AT1-R-induced proliferative effect, resulting in the protective effects on Ang II-induced cardiovasucular and renal action. Thus, elucidation of AT2-R function will be important in clinical treatment with AT1-R antagonists.

Angiotensin II↗
PubMed1998

[Fenestration of diaphragm for management of persistent postoperative pleural effusion: clinical experience and experiment in rabbits].

UNLABELLED: The management of persistent postoperative pleural effusion is still considered difficult. We report here our experience with such a case, successfully managed with fenestration of the diaphragm-the first of it's kind. Clinical Experience: A two-year-old boy with double outlet right ventricle, underwent right heart bypass procedure. Due to low output and high venous pressure, he was on ventilator until the 26th postoperative day. The pericardial and right pleural effusion persisted till the 60th postoperative day. Right phrenic nerve palsy and atelectasis of right lower lobe were suspected to contribute to it. We performed a plication of the right diaphragm and fenestration of the pericardium and right diaphragm. A T-shaped incision was made on the right diaphragm and the edges were trimmed and strengthened with non-absorbable suture into a circular shaped defect of 1.5 cm diameter. The defect was closed with a Dacron mesh allowing passage of fluid across. Pleural effusion decreased immediately and he was discharged a month after the procedure. Experimental Study: The above procedure was experimented in rabbits in whom a contrast medium injected into the pleural cavity could easily drain into the peritoneum through the fenestation, proved by fluoroscopy. CONCLUSION: Fenestration of the diaphragm is an effective procedure to manage persistent pleural effusion.

Animals↗
PubMed1998

[Immune complex-mediated glomerulonephritis associated with infective endocarditis with aortic valve vegetation].

A 61-year-old male was referred to our hospital for rapidly progressive azotemia. He was also found to have huge vegetation at the aortic valve causing regurgitation. Biochemical examinations revealed the presence of an immunocomplex associated with decreased circulating complements. In biopsy samples from the kidney, we found the presence of fibrillar crescents, proliferation of mesangial cells, increase in extracellular matrix proteins, atrophy of tubules, infiltration of mononuclear cells in the interstitial regions, high density deposits in the mesangial area and mesangial interposition. Since the patient strongly rejected operative treatment by valvular replacement, we continued non-invasive treatment such as hemodialysis and treatment with penicillin G. This transiently improved the condition of the patient, including biochemical data and cardiac function, but there was no reduction in the size of vegetation at the aortic valve and the bacteria responsible for infective endocarditis were not identified. About three months after admission, overt signs of congestive heart failure emerged and the patients was subjected to intensive care with a respirator and hemodynamic monitoring. Although the cardiac function was improved, concomitant severe pneumonia occurred and the patient died of septic shock. Thus, we report a rare case in whom immune complex-mediated glomerulonephritis was associated with infective endocarditis with aortic valve vegetation.

Antigen-Antibody Complex↗
PubMed1997

Angiotensin type 2 receptors are reexpressed by cardiac fibroblasts from failing myopathic hamster hearts and inhibit cell growth and fibrillar collagen metabolism.

BACKGROUND: Angiotensin (Ang) II type 1 receptor (AT1-R) induces cardiomyocyte hypertrophy and fibroblast proliferation, whereas the physiological role of AT2-R in cardiac remodeling remains poorly defined. METHODS AND RESULTS: Using Bio14.6 cardiomyopathic (CM) hamsters, we found that AT2-R sites were increased by 153% during heart failure compared with F1B controls. AT1-R numbers were increased by 72% in the hypertrophy stage and then decreased to the control level during heart failure. Such differential regulation of AT2-R and AT1-R during heart failure was consistent with changes in the respective mRNA levels. Autoradiography and immunocytochemistry revealed that both AT2-R and AT1-R are localized at higher densities in fibroblasts present in fibrous regions. Surrounding myocardium predominantly expressed AT1-R, but the level of expression was less than that in fibrous regions. Cardiac fibroblasts isolated from CM hearts during heart failure but not from control hamsters expressed AT2-R (30 fmol/mg protein). Using the cardiac fibroblasts expressing AT2-R, we found that Ang II stimulated net collagenous protein production by 48% and pretreatment with an AT2-R antagonist, PD123319, evoked a further elevation (83%). Ang II-induced synthesis of fibronectin and collagen type I were enhanced by 40% and 53%, respectively, by pretreatment with PD123319. Ang II-induced DNA synthesis (assessed by [3H]thymidine uptake) was significantly increased by PD123319, and the AT2-R agonist CGP42112A reduced the serum-stimulated increase in cell numbers by 23%. Treatment with an AT1-R antagonist, TCV116, for 20 weeks inhibited progression of interstitial fibrosis by 28%, whereas with 44-week PD123319 treatment but not 20-week treatment, the extent of the fibrous region was increased significantly, by 29%. CONCLUSIONS: These findings demonstrate that AT2-R is re-expressed by cardiac fibroblasts present in fibrous regions in failing CM hearts and that the increased AT2-R exerts an anti-AT1-R action on the progression of interstitial fibrosis during cardiac remodeling by inhibiting both fibrillar collagen metabolism and growth of cardiac fibroblasts.

Angiotensin Receptor Antagonists↗
PubMed1997

Membrane localization, topology, and mutual stabilization of the rnfABC gene products in Rhodobacter capsulatus and implications for a new family of energy-coupling NADH oxidoreductases.

The rnf genes in Rhodobacter capsulatus are unique nitrogen fixation genes that encode potential membrane proteins (RnfA, RnfD, and RnfE) and potential iron-sulfur proteins (RnfB and RnfC). In this study, we first analyzed the localization and topology of the RnfA, RnfB, and RnfC proteins. By activity and immunoblot analysis of expression of translational fusions to Escherichia coli alkaline phosphatase, RnfA protein was shown to span the chromatophore membrane with its odd-numbered hydrophilic regions exposed to periplasm. By alkaline treatment of membrane fractions and following immunoblot analysis using antibodies against recombinant proteins expressed in E. coli, both RnfB and RnfC proteins were revealed to situate at the periphery of the chromatophore membranes. Second, mutual interaction of the Rnf proteins was analyzed by immunochemical determinations of RnfB and RnfC proteins in rnf mutants and their complemented derivatives. The contents in cellular fractions indicated that RnfB and RnfC stabilize each other and that the presence of RnfA is necessary for stable existence of both proteins. These results support a hypothesis that the Rnf products are subunits of a membrane complex. Finally, we detected homologs of rnf genes in Haemophilus influenzae and Vibrio alginolyticus by data base searches and in E. coli by cloning of a fragment of an rnfA homolog followed by a data base search. Close comparisons revealed that RnfC has potential binding sites for NADH and FMN which are similar to those found in proton-translocating NADH:quinone oxidoreductases and that RnfA, RnfD, and RnfE show similarity to subunits of sodium-translocating NADH:quinone oxidoreductases. We predict that the putative Rnf complex represents a novel family of energy-coupling NADH oxidoreductases.

Amino Acid Sequence↗
PubMed1997

Acidic fibroblast growth factor (FGF1) increases survival and haematopoietic recovery in total body irradiated C3H/HeNCr mice.

Basic fibroblast growth factor is known to stimulate the proliferation of bone marrow stem and/or progenitor cells in vitro and in vivo. We examined a similar cytokine, acidic fibroblast growth factor (FGF1), for its in vivo radiomodifying effects. Female C3H/HeNCr mice were given human recombinant FGF1 intravenously at doses ranging from 1 to 24 micrograms. FGF1 was delivered in two equal doses 24 and 4 h before or 24 h after otherwise lethal total body irradiation (TBI). In vivo FGF1 radioprotection of C3H mice was maximized at a total dose of 12 micrograms/mouse given before TBI. The radiomodification was 1.16 +/- 0.03 (+/- 1 SD) with an increase of LD50/30 from 736 +/- 9 to 854 +/- 16 cGy (P < 0.01). Some retroactive radiomodification was observed even when FGF1 was given 24 h after irradiation (P < 0.05). FGF1 radioprotected mice by improving the repopulation of haematopoietic progenitor cells of bone marrow. The radioprotection was not associated with an increase in S-phase fraction or detectable circulating IL-3, TNF-alpha or GM-CSF, suggesting that other mechanisms of protection were responsible.

Animals↗
PubMed1997

Calcium equally increases the internal calcium recirculation fraction before and after beta-blockade in canine left ventricles.

We studied whether intracoronary Ca administration after beta-blockade would increase the internal Ca recirculation fraction (RF) analogously to the Ca administration before beta-blockade. This was performed in excised cross-circulated canine hearts. We analyzed the exponential decay component of the postextrasystolic potentiation (PESP) following a spontaneous extrasystole. All the PESPs decayed in alternans with atrial pacing at a constant rate. We obtained the time constant (tau(e)) of the monoexponential decay component of the alternans PESP. An increment of intracoronary Ca by 1.5 mmol/l enhanced the left ventricular contractility index Emax (end-systolic maximum elastance) by 2.5 times before and after beta-blockade with propranolol. The intracoronary Ca after beta-blockade slightly but significantly increased tau(e), and hence increased RF calculated from tau(e) by RF = exp(-1/tau(e)). This was analogous to the slightly increased tau(e) and RF with Ca before beta-blockade. We speculate that the myocardial cyclic AMP-dependent phosphorylation level would not significantly alter the effect of intracoronarily administered Ca on myocardial Ca handling, in terms of tau(e) and RF.

Adenosine Monophosphate↗
PubMed1997

Identification of hepatitis B virus integration in hepatitis C virus-infected hepatocellular carcinoma tissues.

BACKGROUND/AIMS: The integration of HBV DNA is thought to be involved in the initial stage of hepatocarcinogenesis, and it has been reported that transactivating factors encoded by the X and preS2/S genes stimulate transcription of multiple viral and cellular genes. We assessed the possible contributions of hepatitis B virus integration to the occurrence of hepatocellular carcinoma in hepatitis C virus-infected as well as in hepatitis B virus-infected patients by identifying the integrated HBV DNA sequence, and the X and preS2/S regions were further investigated in HBV DNA-integrated cases. METHODS: Southern blot hybridization for detecting HBV DNA in tumor tissues from 28 hepatocellular carcinoma patients was carried out with full-length HBV DNA, and then with X and preS2/S regions as probes. We also carried out reverse transcription-polymerase chain reaction for detecting HCV RNA to confirm hepatitis C virus-infection in liver tissues. RESULTS: Clonally integrated HBV DNA sequences were demonstrated in 16 of 28 patients (57.1%), including five HBsAg seropositive and 11 HBsAg seronegative patients. Of these 11 HBsAg seronegative patients, 10 were also positive for anti-HCV in their sera, and all nine examined cases had HCV RNA in liver. Furthermore, the X region was identified in 14 of 16 HBV DNA integrated cases (87.5%), and the preS2/S region in 6/16 (37.5%). CONCLUSIONS: The present Southern blot analysis demonstrates that clonally integrated HBV DNA sequences were identified even in hepatitis C virus-infected hepatocellular carcinoma patients at a high rate (10/18, 55.6%), and suggests that integrated hepatitis B virus, whose major component is the X gene, may play an important role in hepatocarcinogenesis in hepatitis B virus-integrated cases with and without hepatitis C virus infection.

Adult↗
PubMed1997

beta-Glucosidase in the indigo plant: intracellular localization and tissue specific expression in leaves.

beta-Glucosidase of indigo plant (Polygonum tinctorium) has a high substrate specificity for indican (indoxyl beta-D-glucoside). To examine the localization of this beta-glucosidase, we fractionated the cells of the leaves and analysed them immunocytochemically. Immunoelectron micrographs with specific antibodies against the beta-glucosidase clearly showed that the beta-glucosidase was localized in the stroma of the chloroplasts in mesophyll cells, but not in the thylakoid membrane. Chloroplasts were isolated from the crude homogenate of the fresh leaves by Percoll density gradient centrifugation and then subjected to suborganellar fractionation. beta-Glucosidase activity was specifically detected in the stromal fraction, but not in the thylakoid membrane. This was also supported by the result of an immunoblot of the fraction with anti-beta-glucosidase antibodies. The beta-glucosidase was immunocytochemically localized in the chloroplasts of mesophyll cells, but not in any chloroplasts in marginal cells of the vascular bundle or epidermal cells; ribulose 1,5-bisphosphate carboxylase (Rubisco), a typical stromal protein, was observed in all chloroplasts in these cells. These results suggest that beta-glucosidase is tissue specific in its expression in the leaves of the indigo plant.

Plant Leaves↗