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Biomedical subjects

Y Sakamoto

Publications and source records attributed to Y Sakamoto.

At least 289 records · Page 16Linked to original sources

Impaired glucose uptake and intact gluconeogenesis in perfused rat liver after carbon tetrachloride injury.

The dynamics of glucose movement across perfused livers were assessed in carbon tetrachloride (CCl4)-injured rats. Rats were given CCl4 for 8 weeks and became glucose intolerant and hyperinsulinemic. The fasted rat liver was cyclically perfused with 4 mM lactate and various concentrations (0-20 mM) of glucose for 20 min. In the CCl4-injured liver, net glucose output was less suppressed at high glucose levels than in the normal liver (147 +/- 70 vs 18 +/- 10 mumol at 20 mM glucose, P < 0.05). Deposition of the carbon from [14C] glucose into glycogen was stimulated at high glucose levels and was markedly reduced in the CCl4-injured liver compared to the normal liver (0.58 +/- 0.33 mumol vs 1.44 +/- 0.20 mumol at 20 mM, P < 0.01). Conversion of [14C] lactate to [14C] glucose was not different between the CCl4-injured and the normal liver at each glucose level. Deposition of the carbon from [14C] acetate into glycogen in the CCl4-injured liver was larger than that in the normal liver at 0 mM glucose (0.81 +/- 0.15 mumol vs 0.32 +/- 0.06 mumol, P < 0.01), but was similar to the normal at 20 mM glucose. In the CCl4-injured liver, utilization of exogenous glucose was impaired at high glucose levels, and gluconeogenetic activity was not impaired at low glucose levels. These changes in the hepatic glucose metabolism seem to account for postprandial hyperglycemia without fasting hypoglycemia associated with liver diseases.

Animals↗

Alterations of the cytoskeletal organization in tumor cell lines by a cardiotonic drug, vesnarinone, through protein tyrosine phosphorylation.

We describe nonspecific and moderate activation of cellular protein tyrosine phosphorylation by a chemical compound, vesnarinone, which results in enhanced synthesis and/or assembly of cytoskeletal proteins and morphological alterations in several transformed cells. In A431 cells, vesnarinone induced tyrosine phosphorylation of the overexpressed epidermal growth factor receptors (EGFR) as well as other unidentified proteins, increased the synthesis of cytokeratins, and caused amplification of the intermediate filament networks and cell flattening. The drug effects were abolished by tyrphostin, a protein tyrosine kinase inhibitor. Two other cell lines responded to the drug with increased synthesis of a cell type-specific cytoskeletal protein: vimentin in QG56 human lung carcinoma cells and alpha-tubulin in NIH3T3 cells transformed with v-src. In all cell lines tested, the drug-induced tyrosine phosphorylation was localized in cell-cell and cell-substrate contacts as detected by immunofluorescent staining. Responsive protein substrates and their sensitivity to the drug varied from one cell line to another as observed by immunoblot analysis. Vesnarinone exerted neither activating nor inhibitory effect on in vitro enzyme reactions including EGFR tyrosine kinase, v-src kinase, and protein tyrosine phosphatases. This suggests that vesnarinone indirectly activates tyrosine phosphorylation of membrane proteins related to cell adhesion, which influences a signaling pathway linked to the stress fiber assembly in certain cell lines. The possible mechanism by which vesnarinone induces the cellular responses is discussed.

3T3 Cells↗

Ultrastructural and time-lapse observations of intraepithelial lymphocytes in the small intestine of the guinea pig: their possible role in the removal of effete enterocytes.

In previous ultrastructural studies we have shown that at the tip of intestinal villi in guinea pigs, effete enterocytes are separated into two portions: a thin apical cytoplasm to be exfoliated into the lumen and a major basal portion to be ingested by lamina propria macrophages. During this process, intraepithelially disposed, large granular lymphocytes interdigitate with enterocytes in a complex manner. In the present study, the relation between the enterocytes and the lymphocytes in the villous epithelium of the guinea pig small intestine is described by use of transmission and scanning electron microscopy in an attempt to visualize the roles and activities of the lymphocytes more clearly. The lymphocytes project numerous pointed processes into effete enterocytes, even piercing them. Enterocytes are deeply indented or perforated, probably as a result of the encroaching lymphocyte processes. Some enterocytes are separated into apical and basal portions by numerous large excavations in the cytoplasm. These findings indicate that repeated perforating penetration of the lymphocytes induces cell cleavage. Supporting this supposition, our microcinematographic observations demonstrate the alternate protrusion and withdrawal of processes of lymphocytes. The processes advance with a pointed end, and subsequently, retract with a rounded end in a cycle of 8-18 seconds.

Animals↗

Intravascular ultrasonography of supra-aortic arteries as an adjunct to percutaneous transluminal angioplasty.

We report the intravascular ultrasonographic appearances of three supra-aortic atherosclerotic lesions in two patients before and after percutaneous transluminal angioplasty. Atherosclerotic plaques with calcification and dissection of the arterial wall after percutaneous transluminal angioplasty were demonstrated to better advantage, although they were difficult to see on conventional angiograms.

Aortic Dissection↗

Differential diagnosis of extra-axial intracranial tumours by dynamic spin-echo MRI.

Dynamic MRI was performed on 22 patients with extra-axial intracranial tumours. Serial images were obtained every 30 s for 3 min using a spin-echo sequence (TR 200, TE 15 ms) after rapid injection of Gd-DTPA, 0.1 mmol/kg body weight. The contrast medium enhancement ratio (CER) was correlated with the histology of the tumours. Meningiomas and extra-axial metastases showed a sharp rise, then a gradual decline. Although both had a definite early peak of CER, metastases showed a more rapid decline. Neuromas and extra-axial lymphoma showed a slow, steady increase with no peak within 180 s. This study indicates that the CER is helpful in the differentiation of extra-axial tumours.

Adult↗

Role of the sodium-calcium exchange mechanism and the effect of magnesium on sodium-free and high-potassium contractures in pregnant human myometrium.

OBJECTIVE: Periodic uterine relaxation in labor relieves the fetus from hypoxia related to sustained contractions. A reduction in intracellular calcium is essential for relaxation. Therefore we aimed to clarify the extrusion mechanisms of intracellular calcium ions in pregnant human myometrium. STUDY DESIGN: Isometric contraction of small muscle bundles obtained from human myometrium at term was recorded. High-potassium and sodium-free solutions could induce stable contractures that revealed initial phasic contractions followed by tonic contractions. The effects of external calcium, external magnesium, nifedipine, and calcium adenosine triphosphatase inhibitors on both contractures were then examined. RESULTS: Because maximum tonic contraction was induced by 48 mmol/L potassium, this concentration was used. Both contractures depended on external calcium concentrations. Nifedipine, 10(-7) mol/L inhibited both initial phasic contractions and the tonic phase of the high-potassium contracture; however, it could not suppress the tonic phase of the sodium-free contracture. Calcium adenosine triphosphatase inhibitors, cyclopiazonic acid and lauryl sulfate, potentiated the tensions of tonic phases in both contractures; the effect of lauryl sulfate was stronger than that of cyclopiazonic acid. When external magnesium was gradually increased (from 0 to 9.6 mmol/L), both phasic contractions and the tonic phase of the high-potassium contracture transiently increased, followed by a reduction of tension, whereas the tonic phase of the sodium-free contracture was markedly inhibited by magnesium in a dose-dependent manner. CONCLUSION: The presence of the sodium-calcium exchange mechanism and the specific inhibitory effect of magnesium were indicated in human myometrium during pregnancy. These mechanisms might prevent the long tonic contractions, to protect the fetus from hypoxia during pregnancy and parturition.

Calcium-Transporting ATPases↗

Bile and bilirubin excretion in relation to hepatic energy status during hemorrhagic shock and hypoxemia in rabbits.

OBJECTIVE: We investigated the relation between in vivo hepatocyte excretion of bile and bilirubin and hepatic energy status in rabbit models of hemorrhagic shock and hypoxemia. DESIGN: Randomized animal study. MATERIALS AND METHODS: After creation of a total biliary fistula, hemorrhagic shock with mean pressure of 50 mm Hg (10 rabbits) or hypoxemia with Pao2 at 35 mm Hg (8 rabbits) was induced for 60 minutes. We determined bile flow, excretion of bilirubin and total bile acids, the plasma level of bilirubin, and arterial ketone body ratio, which reflects hepatic mitochondrial function. MEASUREMENTS AND MAIN RESULTS: Both the hemorrhagic shock and the hypoxemic models showed decreases in bile flow and excretion of bilirubin and total bile acids as well as increase in the plasma level of bilirubin in association with decreases in the hepatic energy charge and the arterial ketone body ratio. CONCLUSIONS: Bile flow and the excretion of bilirubin were correlated with the hepatic energy status.

Animals↗

The Bacillus subtilis dnaC gene encodes a protein homologous to the DnaB helicase of Escherichia coli.

Within the region of the Bacillus subtilis chromosome assigned to us in the genome sequencing project, we found a gene, the product of which is similar to the DnaB protein (replicative DNA helicase) of Escherichia coli. Three B. subtilis dna gene mutations, dnaC30 and ts56 causing defects in elongation and ts199 causing a defect in the initiation of replication, were mapped in the gene by transformation and DNA sequencing. Both dnaC30 and ts56 have been located near the amino-terminal end of the B. subtilis DnaC protein. In contrast, ts199 has been located near the carboxy-terminal of the protein. Our results indicate that the B. subtilis dnaC gene encodes a counterpart of the E. coli dnaB helicase.

Amino Acid Sequence↗

[clinical study of balofloxacin on infectious enteritis and assessment of the fecal drug concentration and intestinal microbial flora in patients with inpatients with infectious enteritis. Research group of balofloxacin on infectious enteritis].

The efficacy, safety and usefulness of balofloxacin (BLFX) for patients with acute infectious enteritis and the carriers mainly shigellosis, were investigated. The drug was administered at a daily dose of 200 mg twice a day for 3 days to patients with cholera, 7 days to patients with Salmonella enteritis and 5 days to patients with other conditions of infectious enteritis including shigellosis; 1. The efficacy was analyzed in 89 of the 135 patients who received the administration (43 patients with shigellosis, 14 with Salmonella enteritis, 8 with enteropathogenic/ enterotoxigenic Escherichia coli enteritis, 3 with cholera, 7 with enteritis with other pathogenic bacteria, 6 with polymicrobial infectious enteritis and 8 with acute enteritis that was pathogen-negative). 2. In patients bearing symptoms and who thus could be analyzed for drug efficacy, the drug was markedly effective or effective 50/52 (96.2%). 3. Bacteriologically, the drug was effective for Shigella spp. in 41 (100%) of 41, Salmonella spp. in 12 (85.7%) of 14, and enteropathogenic/enterotoxigenic Escherichia coli in 8 of 8 cases. 4. Adverse effects were seen in 5/133 patients (3.8%) receiving the drug, including two cases of skin eruption, one of the numbness of the hands, one of oral aphtha, and one of nausea. In patients for whom laboratory findings were available, 20/115 (17.4%) showed abnormalities, mainly elevations of GOT and/or GPT, but these were slight. 5. In terms of subjective reports of usefulness, 51/82 (62.2%) were markedly satisfied, and 73/82 (89.0%) were either satisfied or markedly satisfied. 6. The influence of administration of BLFX on fecal concentration and intestinal microbial flora was investigated in 2 patients with acute infectious enteritis. Results approximately equivalent to such flora levels in healthy subjects were obtained. These results suggest that BLFX is highly useful for infectious enteritis such as that caused by shigellosis.

Adolescent↗

Hemifacial spasm: three-dimensional MR images in the evaluation of neurovascular compression.

PURPOSE: To assess the diagnostic accuracy of three-dimensional (3D) magnetic resonance (MR) images in the preoperative evaluation of hemifacial spasm. MATERIALS AND METHODS: In 27 patients with surgically confirmed hemifacial spasm, the axial source images from 3D time-of-flight MR angiography were evaluated for 27 symptomatic sides and 26 asymptomatic sides by three observers in a blinded manner for neurovascular compression and identification of compressive vessels. RESULTS: Sensitivity was 95% and specificity was 77%. Vascular compression on the symptomatic sides could be identified retrospectively in all 27 patients. On the asymptomatic sides, vascular compression could be excluded retrospectively in all but one patient. In the blinded study, as the mean value of three observers, the vertebral artery and posterior inferior cerebellar artery could be identified correctly in seven and 7.7 of seven and nine patients, respectively, whereas the compressive anterior inferior cerebellar artery was identified correctly in 7.7 of 16 patients. CONCLUSION: Three-dimensional MR images have a high diagnostic accuracy and are useful in the preoperative evaluation of hemifacial spasm.

Adult↗

Evaluation of lens transparency changes through photographed images during a 13-month observation period.

Since the development of the anterior eye segment analysis system, several new types of anterior eye segment biometry have been performed. The main aim of this study was to evaluate whether changes in cataractous progression or an increase in lens transparency loss are detectable during a relatively short period of 13 months by measuring the intrapupillary opaque shadow area through retroillumination images or by calculating the light scattering intensity at the deepest cortical layer of the lens through Scheimpflug slit images. Secondly, the relationship between maximally dilated pupil sizes and patients' ages and that between cases with and without diabetes were studied. Thirty-one eyes (49.2%) of sixty-three cataractous lenses showed more than 5% increase in the opaque shadow area. Forty-five eyes (60.0%) showed more than a 5% increase in light scattering intensity. 92.5% of diabetic eyes and 92.3% of nondiabetic eyes showed pupil sizes over 6.5 mm after an instillation of mydriatica. In our study the applied method guaranteed a high reproducibility; thus is might be possible to detect an increase in cataractous changes and lens transparancy in around 50% of examined subjects in a period as short a 1 year. For the evaluation of cataract progression through a retroillumination image, the recommendable pupil size is > or = 6.5 mm.

Aged↗

Computed tomographic images and three-dimensional expression of crystalline lens findings from multiple slices of Scheimpflug slit images.

Although the observation of lens changes in clinical examination has been made through a slit lamp microscope under dilated pupil, precise documentation and analysis of lens changes are presently possible through Scheimpflug photographic images. However, the methodology is still unsatisfactory because the image analysis is two dimensional. In order to overcome this disadvantage, the authors aimed at developing a new methodology for obtaining computed tomographic images of the lens. 60 Scheimpflug slit images of a cataractous human lens were taken by an anterior eye segment analysis system as digital data. After the locations of the whole slit images had been matched, reconstruction of the coronal section line images was performed utilizing extracted image information. The total number of reconstructed coronal section images in additional procedures of the image interpolation was 150. Computed tomography of the lens image was made from those 150 images. A whole lens figure was also demonstrated as a moving three dimensional image.

Aged↗

Intravenous injection of rabbit apolipoprotein A-I inhibits the progression of atherosclerosis in cholesterol-fed rabbits.

The effects of intravenous injection of purified rabbit apoA-I on the progression of aortic atherosclerosis in cholesterol-fed rabbits were examined. In experiment 1, 28 rabbits were equally divided into groups A and B and fed a 0.5% cholesterol diet for 90 days. For the last 30 days, group B received 40 mg apoA-I every week. The fatty streak lesions in group B (23.9 +/- 15.6%) were significantly suppressed compared with those in group A (46.0 +/- 24.9%) (P < .05). In experiment 2, 33 rabbits were divided into four groups (8 or 9 rabbits per group) and fed a 0.5% cholesterol diet. Group A was killed on day 105, while groups B, C, and D were maintained for an additional 60 days on a normal diet, during which time groups C and D received 1 mg apoA-I every other day or 40 mg apoA-I every week, respectively. The lesions in group C (70.2 +/- 15.4%) and group D (65.7 +/- 20.0%) were significantly suppressed compared with those in group B (86.2 +/- 13.7%) (P < .05) but were not reduced to the level of group A (50.0 +/- 22.9%). Although apparent regression was not observed under these conditions, the present study provided the first evidence for the antiatherogenic effect of homologous and apoA-I on the progression of atherosclerosis in cholesterol-fed rabbits.

Animals↗

Levels of cardiovascular risk factors in Japanese people living in the UK.

AIM: We set out to compare levels of cardiovascular risk factors (blood pressure, body mass and serum lipids) in Japanese people living in the UK with those of Japanese people living in Japan and also with residents of the UK. METHODS: Blood samples were taken from individuals attending routine health screening at three centres. The study group comprised 879 men and 723 women born in Japan but living in the UK; 21 248 Japanese men and 8282 Japanese women living in Japan; and 46 623 Caucasian men and 4914 Caucasian women living in the UK. RESULTS: In both men and women we found significantly higher mean blood pressures and cholesterol levels and lower mean triglyceride levels in the expatriate Japanese compared with those still living in Japan. These differences were independent of exercise, smoking and drinking habits and were not related to self-reported levels of stress. They were present even in those Japanese who had been living in the UK for less than 1 year. Higher cholesterol levels were associated with consumption of a Western diet in women but not in men, whereas mean triglyceride levels were lower in men, but not women, eating Western food. CONCLUSION: Our findings suggest that the levels of risk factors such as blood pressure and serum lipids are for the most part culturally, rather than genetically, determined.

Adult↗

Oxytocin stimulates mitogen-activated protein kinase activity in cultured human puerperal uterine myometrial cells.

The regulation of mitogen-activated protein (MAP) kinase by oxytocin in cultured human uterine myometrial cells was investigated. Oxytocin caused the rapid stimulation of MAP kinase activity detected in 32P incorporation of MAP-2. Oxytocin also stimulated the phosphorylation of MAP kinase detected in incorporation of [32P]orthophosphate into MAP kinase. Furthermore, oxytocin induced the tyrosine phosphorylation of MAP kinase. The oxytocin-dependent increase in the tyrosine phosphorylation of MAP kinase displayed a transient time course and was dependent on the concentration of oxytocin applied to the cells. Furthermore, we examined the mechanism by which oxytocin induced MAP kinase phosphorylation. Islet-activating protein (100 ng/ml), which inactivates Gi/Go proteins, blocked the oxytocin-induced phosphorylation of MAP kinase. Moreover, 1 microM ritodrine, which is known to relax uterine muscle contraction, attenuated oxytocin-induced MAP kinase activity and phosphorylation. These results provide evidence that oxytocin acutely activates MAP kinase through an islet-activating protein-sensitive G-protein in human uterine myometrial cells, suggesting that this new pathway may play an important role in the biological action of oxytocin on these cells.

Calcium-Calmodulin-Dependent Protein Kinases↗

Radioimmunoassay method for the determination of 22-oxacalcitriol, a novel analog of 1 alpha,25-dihydroxyvitamin D3 having valuable clinical potency, in rat and human plasma.

22-Oxacalcitriol is a synthetic analog of 1 alpha,25-dihydroxyvitamin D3, which is expected to be a novel agent for the treatment of patients with secondary hyperparathyroidism, psoriasis, and/or breast cancer. A sensitive and practical RIA for 22-oxacalcitriol in rat and human plasma has been developed. A rabbit antiserum raised against 22-oxacalcitriol 3-hemiglutarate conjugated with bovine serum albumin was used in combination with a tritium-labeled 22-oxacalcitriol having high specific radioactivity. A plasma sample was extracted with ethyl ether and the extract was successively purified with Bond Elut C18 and a normal-phase HPLC prior to the RIA to remove interfering substances. Accuracy of the RIA was assessed by various studies including serial dilution and recovery tests. Intra- and inter-assay coefficients of variation were lower than 10%, and the quantification limit was low enough for practical use (33 pg/ml plasma). The present RIA will be useful for the pharmacokinetic studies of 22-oxacalcitriol in both preclinical and clinical stages.

Animals↗