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J Suzuki

Publications and source records attributed to J Suzuki.

At least 91 records · Page 5Linked to original sources
PubMed2000

Positive regulation of skeletal myogenesis by R-Ras.

Most of the proteins in the Ras-family proteins, including Ras, Rap and TC21, have been reported to be strong inhibitors of skeletal myogenesis. Here we show that R-Ras, another member of this family, promotes terminal differentiation of C2C12 skeletal myoblasts. In contrast to Ras, which induced a markedly transformed phenotype of C2C12 cells, an activated mutant of R-Ras (R-RasQ87L) did not exhibit any inhibitory effect on the differentiation of C2C12 cells, but enhanced the formation of multinucleated myotubes. Although R-RasQ87L showed little effect on induction of two muscle-specific proteins, creatine kinase and myogenin, it prevented cell death during myoblast differentiation, probably through Akt activation and Bcl-xL induction. Motility of C2C12 cells, which may be involved in fusion of myoblasts, was also stimulated by R-RasQ87L. Furthermore, we observed a transient activation of endogenous R-Ras during differentiation of C2C12 cells. The ectopic expression of R-Ras GAP inhibited the differentiation. These results suggest that R-Ras has a positive effect on the terminal differentiation of myoblasts and may be involved in the program of skeletal myogenesis.

Animals↗
PubMed2000

Altered expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in acutely rejected myocardium and coronary arteriosclerosis in cardiac allografts of nonhuman primates.

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are important in any process of tissue remodeling. However, there is no report evaluating their expression in cardiac allografts in human or non-human primates. Heterotopic cardiac transplantation was performed on Japanese monkeys. Subjects were treated with chimeric anti-human lymphocyte function-associated antigen-1 monoclonal antibody for 2 weeks. Heart grafts were harvested at days 1-95 (n = 7). Native monkey hearts were used as controls (n = 2). We examined expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 using immunohistochemistry and in situ reverse transcriptase polymerase chain reaction (RT-PCR). In the myocardium, the expression of MMP-2 was increased in the spindle-shaped cells of acutely rejected myocardial interstitium and prior to the presence of mononuclear cell infiltration at days 1-41. TIMP-1 and 2 expression was enhanced in association with the progression of fibrosis at days 40-95. In the coronary arteries of chronically rejected allografts, enhanced MMP and decreased TIMP expression was observed in both thickened intima and media at days 40-95. The medial MMP mRNA expression was observed before the development of intimal thickening occurred at days 7-28. MMPs are critical for the progression of acute and chronic rejection, and TIMP predominance plays important roles in fibrosis in association with acute rejection. Expression of MMPs and TIMPs is a sensitive indicator of acute and chronic cardiac rejection.

Acute Disease↗
PubMed2000

Assessment of renal toxicity by analysis of regeneration of tubular epithelium in rats given low-dose cadmium chloride or cadmium-polluted rice for 22 months.

To determine whether low-dose oral administration of cadmium (Cd) induces renal toxicity, six groups of female Sprague-Dawley rats were fed a diet containing low amounts of CdCl2 or Cd-polluted rice at concentrations up to 40 ppm, and were killed after 12, 18, and 22 months (experiment 1). In addition to the determination of cortical Cd levels and histopathological assessment of kidneys, labeling indices (LIs) for proliferating cell nuclear antigen (PCNA) in the renal cortical tubular epithelium of Cd-treated rats were determined as a measure of regenerative activity. For comparison, the kidneys of rats given diets containing small to large amounts of CdCl2 up to 600 ppm for 4 months were similarly examined (experiment 2). Animals in experiment 1 demonstrated spontaneous chronic nephropathy and fluctuation in the tubular PCNA LI, but these findings were not correlated with renal Cd levels at 22 months. PCNA LI on the other hand, appeared to be linked to the severity of chronic nephropathy. In experiment 2, levels of CdCl2 of 200 ppm or more clearly induced degeneration and apoptosis of proximal tubules with high correlations between renal Cd levels, PCNA LI, and the severity of tubular degeneration. The results demonstrated that, in contrast to high-dose Cd administration, treatment with 40 ppm or less for 22 months did not influence tubular regeneration as a component of nonspecific chronic nephropathy, suggesting that long-term oral administration of low levels of Cd does not injure renal tubules in female rats.

Animals↗
PubMed2000

Ultrastructure of the acidophilic aerobic photosynthetic bacterium Acidiphilium rubrum.

The ultrastructure of cells of Acidiphilium rubrum, which is an acidophilic aerobic photosynthetic bacterium containing zinc-complexed bacteriochlorophyll a, was studied by electron microscopy with the rapid substitution technique. Thin-section electron microscopy indicated that any type of internal photosynthetic membranes was not present in this organism despite a relatively high content of the photopigment. The majority of cells had poly-beta-hydroxybutyrate granules and electron-dense spherical bodies identified as being polyphosphate granules. When the organism was grown chemotrophically with 0.1% FeSO(4), it produced another group of electron-dense granules that were associated with the inner part of the cytoplasmic membrane. An energy-dispersive X-ray analysis showed that these membrane-bound, electron-dense granules contained iron.

Acetobacteraceae↗
PubMed2000

Strength training with partial ischaemia stimulates microvascular remodelling in rat calf muscles.

The effects of strength training with partial tourniquet ischaemia on skeletal muscle capillarity were examined, particularly in terms of the distribution of arteriolar and venular capillaries and their capillary domain area, in male Wistar rats. A tourniquet applied around the knee joint induced partial ischaemia. Repeated isometric contractions of calf muscles, 1 s on/1 s off for 3 min, induced by electrical stimulation (100 Hz), were conducted 2 days/week for 6 weeks as training. Morphologic data were obtained from four groups; non-treatment control (C), ischaemic (IS), non-ischaemic training (NIT) and ischaemic training (IT). In the superficial portion of gastrocnemius (GASs) muscle, the total capillary density of arteriolar capillaries was significantly greater in the IT-leg than in the C-leg (P < 0.05). In the plantaris (PL) muscle, these values were significantly greater in the IT-leg than in both the C- and NIT-legs (P < 0.05). Only in the GASs was the capillary-to-fibre ratio significantly greater in the IT-leg than in the C-leg (P < 0.05). In GASs and PL, the capillary domain area (CDA) was smaller in the IT-leg than in the C- and NIT-legs. In all muscles examined, mean fibre cross-sectional area was not significantly changed by the experimental treatment. These findings suggest that adaptive changes in the microvascular network, identified as an increase in the arteriolar capillary area and a reduction in diffusion distance, occur in the skeletal muscles after strength training with partial ischaemia. These adaptive changes probably improve the supply of oxygen and nutrients to skeletal muscle tissues.

Animals↗
PubMed2000

Antisense Bcl-x oligonucleotide induces apoptosis and prevents arterial neointimal formation in murine cardiac allografts.

OBJECTIVE: Cardiac allograft arteriosclerosis, which limits long-term survival of recipients, cannot be prevented by conservative therapies. The arteriopathy is characterized by diffuse intimal thickening comprised of proliferative smooth muscle cells (SMCs). Cell death is a prominent feature of atherosclerosis; Bcl-x is one of the anti-apoptotic mediators. METHODS: To test the hypothesis that antisense bcl-x oligodeoxynucleotide (ODN) is effective in preventing intimal hyperplasia through enhancing apoptosis after cardiac transplantation, we performed single intraluminal delivery of antisense bcl-x ODN into murine cardiac allografts (n = 9). DBA/2 (H-2d) hearts were transplanted into B10.D2 (H-2d) mice. Sense bcl-x ODN (n = 8) and no treatment (n = 8) studies were also performed. RESULTS: Allografts were harvested at 4 weeks after transplantation; all allografts kept beating throughout the period. Coronary intimal thickening had developed in nontreated and sense ODN transfected allografts at 4 weeks after transplantation with enhanced expression of Bcl-x and cell adhesion molecules, and suppressed apoptosis. However, antisense bcl-x ODN prevented neointimal formation through enhanced apoptosis. CONCLUSION: These results indicate that apoptosis of vascular SMCs induced by Bcl-x is associated with initial hyperplasia after heart transplantation. Antisense bcl-x ODN inhibits SMC proliferation by inducing apoptosis in graft coronary arteries.

Analysis of Variance↗
PubMed2000

Expression of vascular endothelial growth factor and angiogenesis in cardiac myxoma: a study of fifteen patients.

OBJECTIVE: To clarify the association between angiogenesis and the clinicopathologic features in cardiac myxoma, vascular endothelial growth factor expression in the myxoma was examined by using reverse transcriptase polymerase chain reaction and immunohistochemistry, and the microvessel density was determined by counting microvessels in the myxoma by using immunostaining for platelet endothelial cell adhesion molecule 1. METHODS: Seven fresh-frozen and 15 formalin-embedded tissues were analyzed by means of reverse transcriptase polymerase chain reaction and immunostaining for vascular endothelial growth factor, respectively. The microvessel density was measured in the 15 formalin-embedded tissues. Furthermore, immunostaining for proliferating cell nuclear antigen was performed, and the proliferating cell nuclear antigen-labeling index was calculated. RESULTS: All of the 7 analyzed myxomas were positive for vascular endothelial growth factor messenger RNA, as determined by means of reverse transcriptase polymerase chain reaction, whereas atrial septum and atrium tissues were negative. Positive immunohistochemical reaction for vascular endothelial growth factor was observed in the cells of all 15 myxomas. The size of myxomas with high vascular endothelial growth factor expression was smaller than that of myxomas with low vascular endothelial growth factor expression. The microvessel density in myxomas with high vascular endothelial growth factor expression was higher than that in myxomas with low vascular endothelial growth factor expression. There was an inverse correlation between the tumor size and the ratio of the microvessel density in the central part to the microvessel density in the peripheral part of myxomas. Furthermore, there was an inverse correlation between the proliferating cell nuclear antigen-labeling index and the tumor size, and the prolferating cell nuclear antigen-labeling index in myxomas with high vascular endothelial growth factor expression was higher than that in myxomas with low vascular endothelial growth factor expression. CONCLUSIONS: Cardiac myxomas produce vascular endothelial growth factor, which probably induces angiogenesis for tumor growth.

Adult↗
PubMed2000

The influence of left ventricular geometry on coronary vasomotion in patients with essential hypertension.

The objective of this study was to assess the influence of left ventricular (LV) geometric pattern on coronary vasomotion in patients with essential hypertension. We studied 34 hypertensive patients, who had never been treated, with angiographically normal coronary arteries. Patients were classified into four LV geometric patterns by echocardiography: normal, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. The responses of coronary vasomotion in left anterior descending artery to vasoactive agents (acetylcholine, isosorbide dinitrate, adenosine triphosphate) were examined using a Doppler guidewire and quantitative coronary angiography. The percent increase in coronary blood flow evoked with acetylcholine (endothelium-dependent vasomotion) showed lowest in concentric hypertrophy, followed by eccentric hypertrophy, concentric remodeling, and normal geometry. The significant linear relationship between acetylcholine-induced coronary blood flow and LV mass was noted. There was no difference in the percent increase in coronary blood flow evoked with isosorbide dinitrate (endothelium-independent vasomotion of conduit vessel) among the four groups. The percent increase in coronary blood flow evoked with adenosine triphosphate (endothelium-independent vasomotion of resistant vessel) was significantly lower in patients with concentric hypertrophy than in the other three groups. The results in this study suggest that coronary vasomotion may be associated with LV geometry in patients with hypertension. The endothelium-dependent vasodilation is impaired progressively as LV hypertrophy advances. The endothelium-independent vasodilation of microvessels is impaired only in concentric hypertrophy. This advanced abnormality of coronary vasomotion may contribute to the high cardiovascular morbidity and mortality in patients with concentric hypertrophy.

Acetylcholine↗
PubMed2000

Expression of membrane-type 1 matrix metalloproteinase in coronary vessels of allotransplanted primate hearts.

BACKGROUND: The mechanisms of intimal thickening in cardiac allograft vasculopathy (CAV) remain controversial after heart transplantation. Matrix metalloproteinase-2 (MMP-2) plays a crucial role in degrading extracellular matrix (ECM) during neointimal formation. Recently, it has been revealed that MMP-2 is activated by membrane-type 1 matrix metalloproteinase (MT1-MMP). This process involves tissue inhibitor of MMP-2 (TIMP-2), forming an MT1-MMP/TIMP-2/pro-MMP-2 complex. In this study, we hypothesize that these components contribute to the pathogenesis of CAV. METHODS: Heterotopic cardiac allografting was performed in randomly paired Japanese monkeys with an immunosuppressive regimen of intravenous administration of antihuman CD18 monoclonal antibody. The donor hearts were harvested at Days 22, 28, 40, 41, and 95 posttransplantation. We examined expression of MMP-2, MT1-MMP, and TIMP-2 of graft vessels using immunohistochemistry and protein level by western blot analysis. RESULTS: Pathologically, various degrees of neointimal formation were observed. In the allografts harvested at Days 22, 28, 40, and 41, MT1-MMP was expressed in the endothelial cells and smooth muscle cells (SMCs) in media of some arteries without histological change, accompanied by expression of MMP-2 and TIMP-2. In the severely thickened neointima of the allograft harvested at Day 95, MMP-2 and faint MT1-MMP were expressed in SMCs of severely thickened neointima and media; TIMP-2 expression was seen only in noncollagenous tissue of severely thickened neointima. MMP-2 protein was more intensely expressed in the allograft harvested at Day 95 than in the allograft harvest at Day 41, while TIMP-2 protein level was almost same in the 2 samples. CONCLUSION: We observed the simultaneous expression of MMP-2, MT1-MMP, and TIMP-2. Thus, ECM degradation triggered by MT1-MMP/TIMP-2/pro-MMP-2 complex could be a novel mechanism of CAV.

Animals↗
PubMed2000

Autoimmune hemolytic anemia (AIHA) in an infant rhesus macaque (Macaca mulatta).

Autoimmune hemolytic anemia (AIHA) is a disorder associated with the destruction of red blood cells (RBCs) by autoantibodies. We report a rare case of AIHA in an infant rhesus macaque (Macaca mulatta) which received a continuous administration of four drugs, a dopamine agonist. dopamine receptor inhibitor, and two gamma-aminobutyric acid receptor inhibitors into the brain during the course of neurophysiological experiments. The main clinical findings were severe anemia and splenomegaly. Hematological and serological examinations revealed the appearance of peripheral erythroblasts and autoantibodies against RBCs. Medical treatments, including washed RBC transfusion and corticosteroids, transiently improved the animal's anemia, but euthanasia was decided on 331 days after the start of the experiment. The pathological findings revealed severe anemia, splenomegaly, and extramedullary hematopoiesis in the liver and kidneys. These findings and the clinical course suggest that this anemia was a warm-antibody type of AIHA induced by the administration of the drugs for the neurophysiological experiment.

Anemia, Hemolytic, Autoimmune↗