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Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 109 records · Page 6Linked to original sources
PubMed1998

Cutaneous responsiveness of lumbar spinal dorsal horn neurons is reduced by general anesthesia, an effect dependent in part on GABAA mechanisms.

Extracellular activity was recorded from single spinal dorsal horn neurons in both chronic cat and acute rat models. This was done to define the effects of anesthesia on the processing of sensory information elicited by nonnoxious tactile stimulation of peripheral receptive fields (RFs). In the chronic cat model, baseline data were obtained in physiologically intact, awake, drug-free animals before anesthetic administration (halothane 1.0-2.0%). This made it possible to compare and contrast activity of each cell in the drug-free and anesthetized state. Halothane effects were confirmed in the acute rat model (anesthetized, spinally transected, and in some cases decerebrate). In addition, the gamma-aminobutyic acid-A (GABAA)-receptor antagonist picrotoxin (2 mg/kg) was administered intravenously to verify that the observed halothane effect on spinal dorsal horn neurons was mediated by an interaction with GABAA-receptor systems. Halothane effects on three separate measures of response to nonnoxious tactile stimuli were observed in the chronic cat model. Halothane produced a significant, dose-dependent reduction in the low-threshold RF area of the neurons studied. Halothane also caused a significant reduction in neuronal response to RF brushing (dynamic stimulus) and to maintained contact with the RF (static stimulus). A dose dependency was not observed with these latter two effects. Neurons with a predominant rapidly adapting response seemed to be less susceptible to halothane suppression than slowly adapting cells. In the acute rat model an increase in halothane caused a reduction in neuronal response similar to that seen in the cat. The intravenous administration of 2 mg/kg of picrotoxin by itself caused no significant change in RF size or response to brushing. However, the same amount of picrotoxin did cause a 50% reversal of the halothane-induced reduction in RF size without causing a significant change in the halothane effect on response to RF brushing. In contrast to work recently reported in a chronic sheep model, halothane causes a significant reduction in spinal dorsal horn neuronal response to tactile stimulation of peripheral RFs. This effect is caused by, in part, but not exclusively, to GABAA-neurotransmitter systems. However, the relative influence of GABAA systems may vary with the nature of the stimulus.

Action Potentials↗
PubMed1998

[Organ transplantation--approaching the 21st century].

The first clinical kidney transplantation in a chronic renal failure patient in Japan was carried out in March 1964. As of the end of 1997, 12,408 transplantations had been performed; grafts from living donors were used in 8,908, while cadaveric grafts were used in 3,500 recipients. As the next step after enactment of the law concerning human organ transplants, we must endeavor to distribute donor cards and educate people to accept the concept death. At the same time, every effort must be made to establish method for induction of graft tolerance in the clinical setting.

Forecasting↗
PubMed1998

[A case of neurologic type of Wilson's disease with increased aluminum in liver: comparative study with histological findings to metal contents in the liver].

Histological findings and metal contents in the liver were studied in a patient with neurologic type of Wilson's disease. Copper and aluminum contents in the biopsied liver of the patient with Wilson's disease were measured simultaneously by neutron activation analysis at Research Reactor Institute, Kyoto University. Four cases of adult cirrhosis were selected as the control for cirrhosis and five cases of adult liver as the control for neurologically normal. The biopsied liver showed markedly increase in the copper content (814.4 micrograms/g: dry weight) and extremely high content of aluminum (479.4 micrograms/g: dry weight), compared to those of the controls. On the other hand, macroscopically no cirrhosis was observed and the characteristic appearances of macronodular cirrhosis failed to detect histologically. Interestingly the fibrosis or inflammation of the liver was seen faintly. It is likely that toxic metals in the liver such as aluminum, copper and manganese might be implicated in the pathogenesis of neurologic type of Wilson's disease.

Adult↗
PubMed1998

[Use of the radial artery graft in coronary artery bypass grafting: harvesting technique and spasm prevention].

The use of radial artery (RA) in coronary artery bypass grafting (CABG) has been increasing recently as a revival. In this report, we describe several practical suggestions for improving patency rate of the graft. Between April of 1997 and February of 1998, 41 CABGs were performed using RA graft, totalling 56 anastomoses. The early patency rate of the graft has been 100% (graft: 38/38, anastomosis: 53/53). Harvesting technique: with the use of Harmonic Scalpel, it is possible to atraumatically harvest the vessel in a short time. Although longitudinal fasciotomy of the adventitia has been recently reported to be effective in releasing spasm, the nature of the vessel raise concern that the fasciotomy may even induce spasm. We hypothesize that leaving the adventitia intact, preserving vasa vasorum, rather than performing fasciotomy leads to improvement of long-term patency. Spasm prevention: we consider the body temperature to be the most important factor. Therefore, we utilize normothermic cardiopulmonary bypass (CPB). Another important factor is that the arterial CO2 is kept at a high level during CPB. For dilation of RA graft, milrinone is used instead of papaverine. For the intra- and postoperative management, intravenous continuous administration of diltiazem was changed to nicorandil. Technically, essential resolution for improvement of patency rate is either to allow for large proximal anastomosis, or to make sequential anastomosis with another coronary artery which has a good run off. For these purposes, the proximal anastomosis on the ascending aorta seems to have the advantage over placing it on ITA.

Adult↗
PubMed1998

[Phase I study of raltitrexed (ZD-1694)].

A multicenter cooperative phase I study of ZD-1694 (raltitrexed), a novel, folate-based thymidylate synthase (TS) inhibitor, was conducted with single and repeated doses in 30 patients with various malignant tumors. ZD-1694 was intravenously infused over 15 minutes. In the single-dose study, the initial dose was fixed at 1.0 mg/m2 (1n), and the dose was escalated stepwise up to 3.5 mg/m2 (3.5 n). Based on the results of the single-dose study, in the repeated-dose study, doses of 2.5 n and 3 n were infused every three weeks (3 weeks/one course). In principle, patients received 2 courses or more. Of the 29 eligible patients, 16 were in the single-dose study and 13 in the repeated-dose study. Adverse reactions were evaluated in all eligible patients. In the single-dose study, neutropenia, nausea/vomiting, diarrhea, and transaminase (GOT, GPT) increases, of grade 3 or higher, occurred at high doses of 3 n and 3.5 n. These were regarded as dose-limiting toxicities (DLT). DLT of grade 3 or higher were observed in 1 of 4 patients given 3 n and 2 of 4 patients given 3.5 n. These results suggested that the maximum tolerated dose (MTD) of ZD-1694 was 3.5 n (3.5 mg/m2). In the repeated-dose study, DLT of grade 3 or higher was observed in no more than one third of each dose group, 2 of the 6 patients given 2.5 n and 2 of the 7 patients given 3 n. These results suggested that 3 n (3.0 mg/m2), a dose nearer to MTD, was the recommended dose for the phase II study. Although transaminase increases were observed in all patients, in 12 of them the increase was grade 2 or lower and reversible. A pharmacokinetic investigation showed the mean elimination half life of ZD-1694 plasma concentration was 91.5 hours in the single-dose group and 119.1 hours in the repeated dose group. It was suggested that ZD-1694 is metabolized to polyglutamates after uptake and retained in the cells for a long duration. However, no accumulation was seen in plasma concentration of ZD-1694 following repeated doses at 3-weekly intervals. One PR was observed in a patient with colorectal cancer receiving 2.5 n in the repeated-dose study. Based on these results, the recommended dosage and administration for the phase II study of ZD-1694 was 3 n (3.0 mg/m2) intravenously infused over 15 minutes every 3 weeks.

Adult↗
PubMed1997

Comparative study of cytomegalovirus (CMV) antigenemia assay, polymerase chain reaction, serology, and shell vial assay in the early diagnosis and monitoring of CMV infection after renal transplantation.

BACKGROUND: Early diagnosis of cytomegalovirus (CMV) infection, which is an important cause of morbidity and mortality in renal transplant recipients, remains of great importance. This prospective study was performed in kidney transplant recipients to determine the diagnostic value of the CMV antigenemia assay in comparison with polymerase chain reaction (PCR), serology, and shell vial assay. METHODS: Seventy-five consecutive renal transplant recipients were enrolled in this study and monitored by both antigenemia assay and serology. The initial 34 of the 75 patients were subjected to PCR and shell vial assay. RESULTS: Antigenemia, PCR, and shell vial assay became positive before the onset of CMV-related symptoms in 31/34 (89%), 13/16 (81%), and 2/16 (13%), respectively. None of the 34 patients who had symptomatic CMV disease showed a significant increase in IgG or IgM before the onset of symptoms. Antigenemia and PCR assays turned positive, 7 and 11 days (median), respectively, before the onset of clinical symptoms. Serology and shell vial assay became positive 21 and 25 days (median), respectively, after the onset of CMV-related clinical symptoms. To examine the clinical value of these assays, "good correlation" was defined based on the correlation between the clinical course and the results of the assays. Good correlation with the antigenemia assay was observed in 33 (96%) out of 34 renal transplant recipients who recovered from their CMV disease after ganciclovir therapy. Only one of 16 (7%) patients showed good correlation by shell vial assay, whereas PCR and serology did not show a good correlation. Consequently, antigenemia was considered the best way to monitor CMV infections after kidney transplantation. CONCLUSIONS: Only the CMV antigenemia assay can be successfully employed after renal transplantation for the early diagnosis and extensive monitoring of active CMV infection.

Adolescent↗
PubMed1997

The role of the cytoskeleton in migration and proliferation of a cultured human gastric cancer cell line using a new metastasis model.

Using an in vitro model for investigating the mechanism of migration and proliferation of a cultured human gastric cancer cell line which we established recently, we studied the suppressive effect of inhibitors of the cytoskeleton proteins, actin and myosin, on the migration and proliferation of cancer cells. These inhibitors suppressed the capacity of cancer cells to migrate and proliferate dose-dependently. Thus the integrity of the cytoskeletal system may play an important role in the mechanism of metastasis of gastric cancer cells.

Actins↗
PubMed1997

Anti-Ca2+, Mg2+-dependent endonuclease antibody detects specifically a class of chromatin-bound endonuclease.

A polyclonal antibody against purified bull seminal plasma Ca2+, Mg2+-dependent endonuclease was raised in a rabbit. The antibody specifically cross-reacted with chromatin-bound Ca2+, Mg2+-dependent endonucleases from bovine thymus, human placenta, and bovine, rat and mouse liver in addition to the bovine seminal enzyme. The antibody did not cross-react with other endonucleases examined, including the acid-endonucleases from bovine thymus and liver, porcine spleen DNase II, micrococcal nuclease, and bovine pancreas DNase I, a known Ca2+ and Mg2+ requiring endonuclease. The present results indicate that this antibody specifically recognizes a class of so-called Ca2+, Mg2+-dependent endonuclease, which is localized in cell nuclei of various tissues and is probably involved in chromatin degradation during apoptosis. The antibody will be used to study the functional role of this class of endonuclease.

Animals↗
PubMed1997

Developmental regulation and the role of insulin and insulin receptor in metanephrogenesis.

The insulin family of peptides and their receptors influence cellular growth in very early preimplantation embryos. In this study their expression and role in renal organogenesis was investigated. By immunofluorescence microscopy and in situ hybridization, insulin receptor (IR) expression was seen in the ureteric bud branches and early nephron precursors in mouse metanephroi harvested at day 13 of gestation. The expression gradually decreased in successive stages of gestation, and it was confined mainly to renal tubules in 1-week-old mice. Similar developmental regulation of the IR and insulin was observed by reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. Addition of insulin into the culture medium at low concentrations, ranging from 40 to 400 ng/ml, induced trophic changes and increased [3H]thymidine incorporation in the embryonic renal explants, and inclusion of IR beta-subunit-specific antisense oligodeoxynucleotide caused marked dysmorphogenesis and growth retardation of the metanephroi. Specificity of the antisense effect was reflected by immunoprecipitation experiments in which translational blockade of the beta subunit of the IR was observed. RT-PCR analyses revealed that the alpha subunit of the IR was unaffected by the antisense treatment of metanephric explants. Concomitantly, de novo synthesis of morphogenetic regulatory extracellular matrix proteins, especially the proteoglycans, was decreased. Gel-shift analyses indicated a failure in the activation of c-fos promoter region binding protein(s) by insulin in the antisense oligodeoxynucleotide-treated explants. These studies suggest that insulin and its putative receptor are developmentally regulated in the murine embryonic metanephros, and they play a role in renal organogenesis, possibly by affecting other modulators of morphogenesis-i.e., extracellular matrix proteins and protooncogenes.

Animals↗
PubMed1997

Postoperative production of anti-donor antibody and chronic rejection in renal transplantation.

To study the relevance of anti-donor antibody (ADA) to chronic rejection in kidney transplantation, we retrospectively examined the long-term kinetics of ADA by flow cytometric analysis. Among 537 recipients who underwent living-donor kidney transplantation between 1986 and 1994, 29 patients with chronic rejection (CR group) and 33 patients with stable graft function (ST group) were randomly selected for analysis. Patient serum taken 1 or 2 days before transplantation, serum taken 1 month after transplantation, and the most current serum were analyzed for the presence of ADA to donor T and B cells. In the CR group, IgG antibody to donor B cells of the most current serum was positive in 25 of 29 patients, whereas it was positive in only 5 patients in the ST group P<0.001. The mean fluorescent intensity of the antibody was also significantly higher in the CR group than that in ST group P<0.01. In contrast, IgG antibody to donor T cells of the most current serum was positive in only five patients in the CR group. No significant difference was observed in the pretransplant and 1-month posttransplant sera between the CR and ST groups. We conclude that the posttransplant production of IgG antibody to donor B cells seemed to be highly relevant to chronic rejection.

Adolescent↗
PubMed1997

Developmental regulation, expression, and apoptotic potential of galectin-9, a beta-galactoside binding lectin.

Galectin-9, a beta-galactoside binding lectin, has recently been isolated from murine embryonic kidney. In this study, its biological functions and expression in embryonic, newborn, and adult mice tissues were investigated. By Northern blot analyses, it was found widely distributed and its expression was developmentally regulated. In situ hybridization studies revealed an accentuated expression of galectin-9 in liver and thymus of embryonic mice. In postnatal mice, antigalectin-9 immunoreactivity was observed in various tissues, including thymic epithelial cells. The high expression of galectin-9 in the thymus led us to investigate its role in the clonal deletion of thymocytes. Fusion proteins were generated, which retained lactose-binding activity like the endogenous galectin-9. Galectin-9, at 2.5 microM concentration, induced apoptosis in approximately 30% of the thymocytes, as assessed by terminal deoxytransferase-mediated dUTP nick end labeling method. The apoptotic effect was dose dependent and lactose inhibitable. At higher concentrations, it induced homotypic aggregation of the thymocytes. Electron microscopy revealed approximately 60% of the thymocytes undergoing apoptosis in the presence of galectin-9. By immunofluorescence microscopy, some of the thymocytes undergoing apoptosis had plasmalemmal bound galectin-9. Galectin-9 failed to induce apoptosis in hepatocytes. Taken together, these findings indicate that galectin-9, a developmentally regulated lectin, plays a role in thymocyte-epithelial interactions relevant to the biology of the thymus.

Aging↗
PubMed1997

Transplantation of kidneys donated from the USA: long-term results and viability testing using 31P-MRS.

Since June 1983, 27 kidneys have been shipped to the Kidney Center at the Tokyo Women's Medical College (TWMC) from the United States. These organs were divided into two groups, based on the years of their donation; 13 kidneys were assigned to group 1 and 14 to group 2. The differences between the two groups were as follows: donor age 19.8 +/- 10.0 years vs 51.9 +/- 14.5 years in group 2 (P < 0.0001); total ischemic time 42 h 12 min in group 1 vs. 65 h 42 min in group 2 (P = 0.0002); and Euro-Collins preservation solution in group 1 vs University of Wisconsin (UW) solution in group 2. One hundred percent of the kidneys in group 1 and 85.7% of those in group 2 recovered their function. The lowest serum creatinine levels averaged 96 +/- 38.4 mumol/l and 185.8 +/- 101.0 mumol/l, respectively (P = 0.01). The viability of 9 out of 14 grafts in group 2 were tested using 31P magnetic resonance spectroscopy (31P-MRS). The results showed that all of the grafts having a monophosphate/inorganic phosphate (MP/Pi) ratio higher than 0.3 recovered their function and those lower than 0.2 did not. The problems associated with international organ sharing are discussed, along with the difficulties encountered at TWMC.

Adult↗
PubMed1997

Ascorbic acid prevents ischemia-reperfusion injury in the rat small intestine.

Ischemia-reperfusion injury by free radicals and lipid peroxides is observed in various organs. Ascorbic acid (AsA) or glutathione (GSH) in various doses (AsA:2, 0.5, 0.1 mmol/kg, GSH:2 mmol/kg) was intraperitoneally administered to male Wistar rats. The entire small intestines were resected just before ischemia, after ischemia, and after 20 min of reperfusion (n = 7-10 at each time point). At each time point, the specimens were subjected to assays of lipid peroxides, GSH, and glutaminase activity of the tissues; they were also examined histologically. In the AsA group, the production of lipid peroxides after reperfusion was significantly suppressed in a dose-dependent manner, and the ratio of oxidized GSH to total GSH was also significantly low. Tissue glutaminase activity decreased to a lesser extent, and the degree of injury was apparently less marked in the AsA group. This study indicates that AsA acts as an antioxidant against peroxidative tissue injury, possibly by scavenging radicals, preserving reduced GSH, and reducing the peroxidative reaction.

Animals↗
PubMed1997

Ebselen, a novel anti-oxidant compound, protects the rat liver from ischemia-reperfusion injury.

The present study was designed to examine the in vivo effect of ebselen on reperfusion injury to the liver. Lipid peroxidation and glutathione (GSH) levels of the reperfused liver tissue, as well as hepatocellular damage (serum GOT, GPT, LDH, and histology) were examined. The production of thiobarbituric acid-reactive substance did not increase in the 60-min-reperfused liver tissue in the ebselen group. Ebselen completely suppressed the increase in lipid hydroperoxide production in the reperfused liver tissue. After the tissue GSH level was reduced by buthionine sulphoximine, ebselen failed to suppress the lipid peroxidation of the reperfused liver tissue. Serum levels of GOT, GPT, and LDH, histological analysis, and the tissue level of GSH clearly showed that ebselen protects the reperfused liver tissue, both structurally and functionally. We conclude that ebselen's primary effect on ischemia-reperfusion injury may be due to a GSH-peroxidase-like effect and/or the inhibitory effect of leukocyte infiltration.

Alanine Transaminase↗
PubMed1997

Genotype analysis of prepro-vasopressin signal peptide in vasopressin-producing and -non-producing lung tumors.

A polymorphism in the nucleic acid sequence encoding the signal peptide of the human prepro-vasopressin (AVP) has been reported in an AVP producing small cell lung carcinoma (SCLC) cell line. The difference predicts expression in tumor cells of a variant signal peptide with Pro for Leu 11. To clarify whether this difference is required for AVP secretion from SCLC cells and/or reflects increased mutagenesis in malignant tumors, the exon encoding the signal peptide of prepro-AVP in two AVP producing SCLC and 9 non-producing lung tumors was amplified using polymerase chain reaction. The variant sequence was neither found by direct sequencing nor by restriction enzyme analysis. These results suggest that similar to the hypothalamus the normal signal peptide is functional in tumor cells and that the variant signal peptide is not a prerequisite for AVP secretion from SCLC cells.

Animals↗