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Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 289 records · Page 16Linked to original sources
PubMed1998

Protein carbonyl content roughly reflects the unsaturation of lipids in muscle but not in other tissues of stroke-prone spontaneously hypertensive strain (SHRSP) rats fed different fats and oils.

We examined in vivo the effect of dietary fats and oils with different peroxidizability on protein carbonyl content, the presumed index of free radical-mediated protein oxidation. For 15.6 months, SHRSP (stroke-prone spontaneously hypertensive strain) rats were fed a diet supplemented with lard, safflower oil, perilla oil or fish oil/soybean oil, the peroxidizability of which increases in this order. The peroxidizability of tissue lipids was positively correlated with the protein carbonyl content in skeletal muscle, but not in the brain, heart or liver. The protein carbonyl content in the lard group was higher in the brain and liver compared to the other dietary groups. These results contradict the concept that long-term feeding of easily autoxidizable fatty acids allows the accumulation of lipid peroxides to accelerate the development of the free radical diseases, and suggest that tissue protein carbonyl content is not a simple reflection of autoxidizability-related lipid peroxidation but is also influenced by other biochemical processes.

Aging↗
PubMed1998

Coronary thrombosis. Effects of blood flow on the mechanism of thrombus formation.

The mechanism of arterial thrombosis, including coronary thrombosis, is different from that of thrombosis which occurs at sites of blood stasis such as deep venous thrombosis. Considering the onset of arterial thrombus formation, soluble coagulant factors may not play important roles for its onset since they are diluted by the effect of blood flow and cannot reach high enough concentrations to form insoluble fibrin. Platelets, which can stick to damaged vascular lumen even in the presence of shearing effects of blood flow, may play a crucial role in the onset of arterial thrombus formation. Thus, the mechanism of platelet thrombus formation should be assessed in the presence of blood flow. However, current dogma that fibrinogen binding to activated GP IIb/IIIa is the final common pathway for platelet thrombus formation was developed by using the function assay system of aggregometer, in which the effects of blood flow were not seriously considered. We are proposing in this review that plasma ligand protein of von Willebrand factor (vWF) and its interactions with platelet GP lb and GP IIb/IIa, which become apparent only in assays systems under influence of high shear rates of flow condition such as flowchambers or coneplate viscometers, are the key events leading to the onset of arterial thrombosis. A better understanding of the vWF-mediated mechanism of platelet thrombus formation is important for the development of better clinical tools to prevent ischemic heart disease as well as for a complete understanding of the mechanism of coronary thrombosis.

Blood Circulation↗
PubMed1998

Expression and localization of cyclooxygenase isoforms and cytosolic phospholipase A2 in anti-Thy-1 glomerulonephritis.

Glomerular expression of the major rate-limiting enzymes for prostanoid synthesis, cyclooxygenase isoforms (COX-1 and COX-2) and cytosolic phospholipase A2 (cPLA2), was investigated in anti-Thy-1 nephritis in rats. Ribonuclease protection assay demonstrated minimal COX-1 mRNA expression in glomeruli of control rat kidneys and a gradual increase of expression from day 1 to day 10 after administration of monoclonal anti-rat Thy-1 antibody. On the other hand, COX-2 mRNA expression, also minimal in the normal glomeruli, was enhanced in a biphasic pattern with two peaks at 1 h and day 10. Expression of cPLA2 mRNA, which was undetectable in normal glomeruli, was induced on day 1 and increased gradually in a pattern similar to that of COX-1 mRNA expression. Immunofluorescence microscopy, using antibodies against COX isoforms, showed that both COX-1 and COX-2 were negligible or faintly detectable in the glomeruli of control rat kidneys. In contrast, the immunofluorescence for COX-1 was intensified on days 4 and 10 along the glomerular capillary walls probably in glomerular epithelial and/or endothelial cells, whereas COX-2 staining was exclusively enhanced in the glomerular epithelial cells at 1 h and day 10 during the course of anti-Thy-1 nephritis. These findings indicate that prostanoids generated through induction of COX-1, COX-2, and cPLA2 are implicated in the mediation of the mesangial cell injury model. In particular, the upregulation of COX-2 expression in glomerular epithelial cells in the selective mesangial cell injury model suggests an intercellular interaction between mesangial cells, and glomerular epithelial cells.

Animals↗
PubMed1998

Involvement of R-cadherin in the early stage of glomerulogenesis.

The earliest commitment to the formation of glomeruli is recognizable in S-shaped bodies. Although cell-cell adhesion seems likely to play a crucial role in this process, how glomerular epithelial cells segregate from the other parts of the nephron is unknown. In this study, immunofluorescence microscopy and monoclonal antibodies specific for mouse R-, E-, P- and N-cadherins were used to examine which of these adhesion molecules are involved in glomerulogenesis of the mouse kidney. Weak R-cadherin staining was first found in the vesicle stage, becoming restricted to glomerular visceral epithelial cells (VEC) during the S-shaped body stage. The intensity of this staining became stronger in the capillary loop stage, whereas parietal epithelial cells (PEC) and tubular cells did not stain. In the maturing stage, VEC gradually lost their staining for R-cadherin. E-cadherin was detected in ureteric buds and the upper limb of S-shaped bodies. From the capillary loop to the maturing stage, anti-E-cadherin stained epithelial cells in all tubule segments, but no label was seen in VEC or PEC. P-cadherin was also stained in the ureteric buds and in the upper limb of S-shaped bodies. N-Cadherin was weakly stained in cells at the vesicle stage, but thereafter staining of N-cadherin was not detected at any stage of glomerular formation. Immunoelectron microscopy of differentiating VEC was performed using antibodies specific to alpha-catenin, which is associated with cadherin. Subsequently, immunogold particles identifying alpha-catenin were localized on junctions between primary processes of VEC. These findings indicate that R-cadherin is uniquely expressed in differentiating VEC, suggesting an important role in the early stages of glomerulogenesis.

Animals↗
PubMed1998

Diminished kidney function and nephrocalcinosis in rats fed a magnesium-deficient diet.

The effect of a magnesium-deficient diet on kidney function was studied in young male rats. The rats were fed a purified diet with a magnesium content of either 20.5 (control diet) or 2.6 mmol/kg (magnesium-deficient diet) for 21 d. In rats fed the magnesium-deficient diet, kidney wet and dry weights were significantly increased, and calcium and phosphorus concentrations in the kidney were significantly higher than in rats fed the control diet. Upon histological examination, an increase in the mesangial matrix of the glomeruli and injury to the brush border of the proximal tubules were observed in rats fed the magnesium-deficient diet. Also, a deposition of calcium was observed in the tubules of the corticomedullary junction and medulla of these rats. Total protein and albumin concentrations in serum were significantly decreased in rats fed the magnesium-deficient diet. Urinary albumin excretion was significantly higher, and N-acetyl-beta-D-glucosaminidase activity in the urine was significantly increased in rats fed the magnesium-deficient diet. These findings indicate diminished glomerular and proximal tubular functions. We suggest that a magnesium-deficient diet not only induces nephrocalcinosis, but it also diminishes kidney function.

Acetylglucosaminidase↗
PubMed1998

Effects of iron and copper supplementation on the formation of thiobarbituric acid-reactive substances and phosphatidylcholine hydroperoxide in the livers of iron- and copper-deficient rats.

Free radicals and lipid peroxide formation are related to tissue damage. This damage is thought to be associated with various diseases. To accurately assess the degree of lipid hydroperoxidation in biological materials, three different thiobarbituric acid (TBA) assay methods and the measurement of phosphatidylcholine hydroperoxide (PCOOH) by the chemiluminescence-HPLC (CL-HPLC) method were compared. Iron and copper deficiencies in rats reduced the contents of these metals. The addition of iron and copper to liver homogenates produced dose-dependent increases and decreases in TBARS, respectively. TBARS measured by the Shinnhuber method slightly increased with the addition of copper. The measurement of PCOOH was less affected by the addition of these metals. TBARS did not reflect lipid peroxidation when different concentrations of metals were present in the samples. The TBARS level is thus not a suitable marker for the assess of lipid peroxidation. PCOOH, accumulated as a primary peroxidation product from membrane phospholipids in the liver, was found to be a more appropriate marker for the estimating hepatic lipid peroxidation in the iron- and/or copper-deficient condition.

Animals↗
PubMed1998

Systematic Prediction of Orthologous Units of Genes in the Complete Genomes.

In order to fully make use of the vast amount of information in the complete genome sequences, we are developing a genome-scale system for predicting gene functions and cellular functions. The system makes use of the information of sequence similarity, the information of positional correlations in the genome, and the reference knowledge stored as the ortholog group tables in KEGG (Kyoto Encyclopedia of Genes and Genomes). The ortholog group table summarizes orthologous and paralogous relations among different organisms for a set of genes that are considered to form a functional unit, such as a conserved portion of the metabolic pathway or a molecular machinery for the membrane transport. At the moment, the ortholog group table is constructed for the cases where the genes are clustered in physically close positions in the genome for at least one organism. In this paper, we describe the system and the actual analysis of the complete genome of Pyrococcus horikoshii to identify ABC transporters.

Journal Article↗
PubMed1998

[Efficacy of granisetron, a 5-HT3 antagonist, in the prevention of nausea and vomiting induced by conditioning for hematopoietic stem cell transplantation].

One hundred and eleven patients receiving conditioning regimens for hematopoietic stem cell transplantation (HSCT) were administered a single intravenous dose (40 micrograms/kg) of granisetron before chemo-radio therapy. The efficacy of the drug was assessed every 24 hours, rating the control of nausea and vomiting as complete, major, minor or failure. On day 1, 23 of 48 patients (47.9%) who received cyclophosphamide (60 mg/kg/day), achieved control of emesis with complete or major response. On day 2, 17 of 47 patients (36.2%) achieved control emesis. During total body irradiation (TBI) (10 approximately 12 Gy/2 approximately 3 days), 21 of 33 patients (63.6%) achieved control of emesis on day 1 and 22 of 32 patients (68.6%) achieved control of emesis on day 2. During melphalan administration (60 approximately 100 mg/m2/day), 20 of 28 patients (71.4%) achieved control of emesis on day 1. Adverse effects were observed in seven patients but were not serious. We concluded that granisetron has a major role in preparation for HSCT.

Adolescent↗
PubMed1998

[Adult multiple coronary aneurysms of Kawasaki's disease's sequelae; two autopsy cases].

Coronary aneurysm in Kawasaki's disease (Acute febril infantile mucocutaneous lymph node syndrome, MCLS) may cause sudden death in childhood and ischemic heart disease in adults. We encountered two adult autopsy cases of Kawasaki's disease with multiple coronary aneurysms. The first case was a 56-year-old man who hospitalized due to recurrent syncope since 51 years of age. At age 55 coronary angiography (CAG) had shown multiple aneurysms in the left and right coronary artery. In September 1991, he developed chest pain and was brought to the hospital, almost dead on arrival (DOA). The patient died later the same day despite cardiopulmonary resuscitation. Autopsy findings showed cardiomegaly (470 g) with multiple coronary aneurysms of three coronary arteries. Microscopically, intimal thickening and medial thinning were found in the aneurysmal wall with calcification and disruption of the internal elastic lamina. The second case, a 28-year-old man had been diagnosed with rheumatic fever and mitral regurgitation at 4 years of age. Coronary aneurysms were noted on CAG at 26 years of age. In April 1992, he developed fever and was admitted to a local hospital where he was diagnosed with infectious endocarditis. After his being transferred to our hospital, disturbance of consciousness suddenly developed and he died in September 1992. Autopsy findings showed cardiomegaly (430 g) with left ventricular hypertrophy and multiple coronary aneurysms in left anterior descending coronary artery and left circumflex coronary artery. The aneurysmal wall showed intimal thickening and medial thinning with multiple recanalizations of occlusive lumina and fibrous intimal thickening. The mitral valve showed mild fibrosis and calcification without valvular deformity. There was no evidence of bacterial endocarditis. Both cases were finally diagnosed as Kawasaki's disease. Ischemic heart disease or lesions related to coronary aneurysm in Kawasaki's disease may show an increased incidence in the near future. Kawasaki's disease should have been followed even in adulthood after treatment in childhood.

Adult↗
PubMed1998

Intraoperative Doppler ultrasound in liver transplantation.

The purpose of this study was to determine the utility of intraoperative Doppler ultrasound for the diagnosis and reduction of the vascular complications in liver transplantation. This study included 19 pediatric and 5 adult patients. In the pediatric group, 12 patients received living related liver transplantation (LRLT), two splitting liver transplantation (SLT), three reduced-size liver transplantation (RLT) and two full-size pediatric liver transplants (FPLT). The hemodynamics and waveform of the hepatic vein, portal vein and hepatic artery were evaluated by intraoperative Doppler ultrasound (US) after reperfusion of the graft. Unsatisfactory hemodynamics was identified in nine cases, including decrease hepatic venous flow (6-9 cm/s) with non-pulsative flat waveform (adults, n = 2 and LRLT, n = 2); portal vein thrombosis (LRLT, n = 1); decrease portal flow (8 mL/min/kg) (LRLT, n = 1); occlusion of the portal vein (SLT, n = 1); poor arterial flow with dampened artery waveform (FPLT, n = 2). These abnormalities were all successfully re-reconstructed by surgical procedures and achieved a graft survival rate of 100%. Two late vascular complications including hepatic venous thrombosis and recurrent portal vein stenosis with splenorenal shunt were discovered 1 month later. They were treated effectively by surgical thrombolectomy and percutaneous balloon dilatation and metallic coils embolization respectively. Three patients died of non-vascular complications and all patients who underwent LRLT survived with a resultant 87.5% overall survival rate. In conclusion, intraoperative Doppler US is efficient in detecting abnormal hepatic hemodynamics, which permits early intervention and hence a better prognosis for the patients. Re-reconstructive procedures were monitored closely under Doppler US guidance until proper flow and wave-form were established. This reduces post-transplant vascular complications and thereby eliminates the likelihood of a lethal complication that might call for re-transplantation.

Adolescent↗
PubMed1998

DBGET/LinkDB: an integrated database retrieval system.

The integrated database retrieval system DBGET/LinkDB is the backbone of the Japanese GenomeNet service. DBGET is used to search and extract entries from a wide range of molecular biology databases, while LinkDB is used to search and compute links between entries in different databases. DBGET/LinkDB is designed to be a network distributed database system with an open architecture, which is suitable for incorporating local databases or establishing a specialized server environment. It also has an advantage of simple architecture allowing rapid daily updates of all the major databases. The WWW version of DBGET/LinkDB at GenomeNet is integrated with other search tools, such as BLAST, FASTA and MOTIF, and with local helper applications, such as RasMol. In addition to factual links between database entries, LinkDB is being extended to included similarity links and biological links toward computerization of logical reasoning processes.

Databases, Factual↗
PubMed1998

High concentration of L-arginine suppresses nitric oxide synthase activity and produces reactive oxygen species in NB9 human neuroblastoma cells.

Hereditary argininemia manifests as neurological disturbance and mental retardation, features not observed in other amino acidemias. The cytotoxic effect of a high concentration of L-arginine (L-Arg) was investigated using NB9 human neuroblastoma cells (NB9), which express neuronal nitric oxide synthase (nNOS). When the concentration of L-Arg in the medium increased from 50 microM to 2 mM after incubation for 48 hr, the intracellular concentration of L-Arg increased from 68.0 +/- 1 pmol/10(6) cells to 1310.0 +/- 5 pmol/10(6) cells and that of L-citrulline (L-Cit) from undetectable levels to 47.1 +/- 0.2 pmol/10(6) cells (mean +/- SD of three independent analyses). This increase in intracellular L-Arg levels caused a decrease in NOS activity by approximately 71%. Flow cytometric analysis showed that reactive oxygen species (ROS) are produced in NB9 exposed to 2 mM L-Arg. The production of ROS was abolished by a NOS inhibitor, NG-nitro-L arginine-methylester. Production of ROS was also observed when NB9 were treated with L-Cit for 48 hr. To investigate the effect of L-Cit on the activity of NOS, a kinetic study on nNOS was conducted using cellular extracts from NB9. The apparent Km value of nNOS for L-Arg was 8.4 microM, with a Vmax value of 8.2 pmol/min/mg protein. L-Cit competitively inhibited NOS activity, as indicated by an apparent Ki value of 65 nM. These results suggest that L-Cit formed by nNOS in L-Arg-loaded neuronal cells inhibits NOS activity and nNOS in these L-Arg-loaded cells functions as a NADPH oxidase to produce ROS, which may cause neurotoxicity in argininemia.

Arginine↗
PubMed1998

Post-transplant changes of segment 4 after living related liver transplantation.

The purpose of this study was to evaluate the outcome of the medial segment of the graft after living related liver transplantation (LRLT). Of the 12 pediatric recipients who underwent LRLT, 2 received whole left liver graft, 1 left lateral segment graft, and 9 extended left lateral segment grafts. The hepatic veins of the donor were reviewed and the volume of the medial segment and left lateral liver was measured before and 6 months after liver transplantation. The flow velocity and direction of the portal vein in the medial segment graft was also evaluated by Doppler ultrasound. The grafted livers of all recipients showed a substantial increase in volume of 9-120% 6 months after LRLT. For the left lateral segment, an increase in volume was found in all cases ranging from 21 to 245%. For the medial segment, volume increases of 5-48% were found in seven cases with normal hepatopetal flow detected inside the segment 4 intrahepatic portal vein. In four cases, the partial medial segment graft of the extended left lateral liver graft decreased in volume from 33 to 69%. Among these four cases, slow flow (n = 2) and hepatofugal flow (n = 1) were also detected in the intrahepatic portal vein of the medial segment. Mapping of the tributary of the hepatic veins of the graft revealed inadequate venous drainage of the partial segment 4 graft, which may be considered as the cause of the atrophic change of the partial segment 4 graft. In conclusion, different regenerative rates between the left lateral segment and the medial segment were noted, with a greater rate in the left lateral segment. The venous drainage of the medial segment is of primary concern in the determination of the outcome of the regeneration. Atrophic change occurs when inadequate hepatic venous drainage is encountered. Therefore, if an extended left lateral liver graft is required, the corresponding draining veins of the partial medial segment must be preserved. Otherwise, whole left liver or left lateral segment graft would be a better choice.

Blood Flow Velocity↗
PubMed1998

Pathophysiology and treatment of cerebral ischemia.

This article describes the pathophysiology of, and treatment strategy for, cerebral ischemia. It is useful to think of an ischemic lesion as a densely ischemic core surrounded by better perfused "penumbra" tissue that is silent electrically but remains viable. Reperfusion plays an important role in the pathophysiology of cerebral ischemia. Magnetic resonance imaging (MRI) and histological studies in rat focal ischemia models using transient middle cerebral artery (MCA) occlusion indicate that reperfusion after an ischemic episode of 2- to 3-hour duration does not result in reduction of the size of the infarct. Brief occlusion of the MCA produces a characteristic, cell-type specific injury in the striatum where medium-sized spinous projection neurons are selectively lost; this injury is accompanied by gliosis. Transient forebrain ischemia leads to delayed death of the CA1 neurons in the hippocampus. Immunohistochemical and biochemical investigations of Ca2+/calmodulin-dependent protein kinase II(CaM kinase II) and protein phosphatase (calcineurin) after transient forebrain ischemia demonstrated that the activity of CaM kinase II was decreased in the CA1 region of the hippocampus early (6-12 hours) after ischemia. However, calcineurin was preserved in the CA1 region until 1.5 days after the ischemic insult and then lost; a subsequent increase in the morphological degeneration of neurons was observed. We hypothesized that an imbalance of Ca2+/calmodulin dependent protein phosphorylation-dephosphorylation may be involved in delayed neuronal death after ischemia. In the treatment of acute ischemic stroke, immediate recanalization of the occluded artery, using systemic or local thrombolysis, is optimal for restoring the blood flow and rescuing the ischemic brain from complete infarction. However, the window of therapeutic effectiveness is very narrow. The development of effective neuroprotection methods and the establishment of reliable imaging modalities for an early and accurate diagnosis of the extent and degree of the ischemia are imperative.

Adaptation, Physiological↗
PubMed1997

Effect of estrogen on nitric oxide-induced relaxation of the rabbit urethra.

We evaluated the effect of estrogen on nitric oxide (NO)-mediated urethral relaxation in rabbits. Female New Zealand white rabbits, 4-5 weeks old, were treated with 5 mg/kg estradiol dipropionate (estrogen group) or saline (control group) injected intramuscularly weekly for 2 weeks. Electrical field stimulation (supramaximum voltage, 2 ms pulse duration, 0.3-15 Hz and 3 s train) caused frequency-dependent relaxation of urethral strips in both groups, which was inhibited by Nomega-nitro-L-arginine (L.-NNA). This inhibition was overcome by addition of L-arginine. The relaxation induced by nitrergic nerve stimulation was significantly lower in the estrogen group than in the control group. There was no significant difference in sodium nitroprusside-induced urethral relaxation between the two groups. The production of NO in urethral strips during nitrergic nerve stimulation was evaluated by measuring nitrite/nitrate (NO2-/NO3-) levels in both groups, using microdialysis. The NO2-/NO3- production during electrical field stimulation in the estrogen group was significantly less than that in the control group. The NADPH diaphorase-positive reaction in the control group was greater than that in the estrogen group. The results suggest that estrogen treatment may reduce NO synthase activity, and inhibit the relaxation induced by nitrergic nerve stimulation in rabbit urethral smooth muscle.

Adrenergic beta-Antagonists↗
PubMed1997

Expression and localization of the Na-K-2Cl cotransporter in the rat cochlea.

We identified the localization of the basolateral bumetanide-sensitive Na-K-2Cl cotransporter (BSC2) in the cochlea using an in situ hybridization method. In the rat cochlea, the BSC2 mRNA was mainly expressed in the strial marginal cells. Although the fibrocytes localized at the spiral prominence showed a weak expression of BSC2 mRNA, no expression was observed in the organ of Corti or spiral ganglion cells. The present findings are well consistent with a proposed cell model of ion transport in the marginal cell.

Animals↗