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Biomedical subjects

Y Kosaka

Publications and source records attributed to Y Kosaka.

At least 91 records · Page 5Linked to original sources
PubMed1996

Antinociceptive effects of ONO-9902, an enkephalinase inhibitor, after visceral stress condition in rats.

PURPOSE: The present study was designed to examine the antinociceptive effects of orally administered ONO-9902, an enkephalinase inhibitor, on both somatic and visceral pain after visceral stress conditions. METHODS: Twenty six male rats were examined. Tail-flick (TF) and colorectal distension (CD) tests were used to determine somatic and visceral antinociceptive effects, respectively. Measurements were performed in rats under immediate post-stress conditions (group ST; n = 14) and in rats nor under stress conditions (group NST; n = 12). In the stressed group, the same device, CD, for visceral antinociceptive effects was used for visceral stress and was applied with an intracolonic pressure of 60 mmHg for 20 min after drug administration. The TF latency and CD threshold were measured before and at 30, 40, 50, 60 and 90 min after administration of ONO-9902 300 mg.kg-1 or distilled water. RESULTS: Orally administered ONO-9902 did not produce any changes in the % maximum possible effect (%MPE) in either TF or CD tests in the unstressed group. In the stressed group, %MPE in the CD test increased 18% and 31% at 30 and 40 min, respectively, after oral administration of ONO-9902 compared with the control group (P < 0.05). However, %MPE to TF test did not alter even after the CD-induced stress condition. CONCLUSION: These results suggest that ONO-9902 may have analgesic effects on visceral pain but not on somatic pain under immediate post-stress conditions.

Analgesics, Non-Narcotic↗
PubMed1996

Infection with GB virus C (GBV-C) in patients with fulminant hepatitis.

BACKGROUND/METHODS: There appear to be hepatitis viruses other than hepatitis A, B, C, D and E. One of these has been proposed with a designation of GB virus C. Sera from 44 patients with fulminant hepatitis were tested for RNA of GB virus C by reverse-transcription polymerase chain reaction with nested primers deduced from the putative non-structural 3 (helicase) region. RESULTS: RNA of GB virus C was detected in three (20%) of 15 patients with hepatitis B virus infection and three (12%) of 25 patients without markers of hepatitis A-E virus infection. Overall, GB virus C RNA was detected in six (14%) of the 44 patients with fulminant hepatitis, at a frequency significantly higher (p < 0.001) than that in three (0.9%) of 326 blood donors matched for age with the patients. CONCLUSIONS: These results indicate a role of GB virus C in inducing fulminant hepatitis either by itself or in concert with the other hepatitis viruses.

Acute Disease↗
PubMed1996

Fulminant hepatic failure caused by ecarazine hydrochloride (a hydralazine derivative).

The cause of fulminant hepatic failure is reported to be unknown in more than half the cases in Japan. We recently reviewed 23 cases of fulminant hepatic failure that had been treated at our hospital. The cause of disease had been regarded as unknown before this study. It was found that seven of these patients had been under ecarazine hydrochloride therapy when they developed fulminant hepatic failure. We examined the reasons why fulminant hepatic failure in these seven patients had not been previously attributed to ecarazine, and found that it could be explained by the following factors: (1) the time from the start of ecarazine therapy to the onset of hepatic failure was long; (2) in all cases, hepatic failure developed more than 10 days after the clinical recognition of hepatitis; and (3) characteristic signs of drug-induced hepatic failure such as a skin rash and positive lymphocytes stimulation test with the drug were absent in all cases. Fulminant hepatic failure in these cases could be characterized by: (1) rapid decrease in serum alanine transaminase (ALT) level after discontinuation of ecarazine, (2) prolonged jaundice despite discontinuation of ecarazine, (3) high incidence of anti-nuclear antibody (ANA) (57%), and (4) histological findings of extensive hepatocellular necrosis ranging from bridging necrosis to massive necrosis. Of the seven patients, four died of fulminant hepatic failure. These four patients had received high doses of ecarazine hydrochloride for prolonged periods. Our data suggest that there may be many cases in which the cause of fulminant hepatic failure or acute hepatitis was not previously determined that can be attributed to long-term drug therapy for chronic diseases.

Adult↗
PubMed1996

The effects of epidural anesthesia on ventilatory response to hypercapnia and hypoxia in elderly patients.

Epidural anesthesia may impair pulmonary ventilation in elderly people. We examined the effects of lumbar or thoracic epidural anesthesia on resting ventilation, arterial blood gas tensions, the ventilatory response to hypercapnia, and progressive isocapnic hypoxia in elderly patients. Two groups of eight unpremedicated elderly patients, aged 65 yr or older, undergoing lower or upper abdominal surgery, respectively, were studied twice before and 20 min after the lumbar or thoracic administration of 10 mL of 2% lidocaine. Lumbar epidural anesthesia had no significant effect on resting ventilation, whereas thoracic epidural caused a significant 13% decrease in minute ventilation and a 14% decrease in tidal volume (P < 0.05). The ventilatory response to hypercapnia was significantly increased after lumbar epidural anesthesia, but no change was observed after thoracic epidural anesthesia. The slope of the hypoxic response curve did not show any change in either group, but minute ventilation at a Spo2 of 90% significantly increased after lumbar epidural anesthesia (P < 0.05). We conclude that neither lumbar nor thoracic epidural anesthesia per se impairs the ventilatory response to hypercapnia and hypoxia, despite slight impairment in resting ventilation by thoracic epidural anesthesia, in elderly patients.

Aged↗
PubMed1996

A new CYP2D6 allele with a nine base insertion in exon 9 in a Japanese population associated with poor metabolizer phenotype.

The CYP2D6 gene of a Japanese sparteine poor metabolizer (PM, proband) showing a urinary sparteine metabolic ratio of 31.6 was analysed, and a heterozygous CYP2D6(D), a deletional type, was found by restriction fragment length polymorphism analysis with Xba I enzyme. The PM did not have any other previously described mutations in the CYP2D6 gene causing the loss of catalytic activity of the CYP2D6 enzyme. Thus, a possible new allele(s) responsible for the PM phenotype was analysed. The results indicated that the PM possessed a new 9-base insertion in exon 9, designated CYP2D6(J9). The CYP2D6(J9) and CYP2D6(D) alleles were clarified to be inherited from the mother [2D6(W)/2D6(J9)] and the father [2D6(W)/2D6(D)], respectively. The 9-base insertion caused a large increase in the apparent K(m) value for bufuralol 1'-hydroxylation as examined by expression of the enzyme protein in yeast. Four of 300 Japanese carried a heterozygous CYP2D6(J9) allele (0.7%, 4/600 chromosomes) as determined by a polymerase chain reaction analysis.

Alleles↗
PubMed1996

Herbal medicine 'Sho-saiko-to' induces tumour necrosis factor-alpha and granulocyte colony-stimulating factor in vitro in peripheral blood mononuclear cells of patients with hepatocellular carcinoma.

'Sho-saiko-to' (TJ-9) is a Japanese herbal medicine that is commonly administered to patients with chronic viral liver disease in order to improve their overall physical condition and to prevent the development of liver cancer, The present in vitro study demonstrated that, by adding TJ-9 to cell cultures, there were dose-dependent increases in production levels of tumour necrosis factor-alpha (TNF-alpha) and granulocyte colony-stimulating factor (G-CSF) in peripheral mononuclear cells of patients with hepatocellular carcinoma accompanied by liver cirrhosis. Increases in the production of TNF-alpha and G-CSF in control cell cultures exposed to different herbal medicines were low, and this indicates the specificity of the response increases in production of these cytokines to TJ-9. TNF-alpha and G-CSF are known to play important roles in the biological defence mechanism. Administration of TJ-9 may, therefore, be beneficial for patients afflicted with intractable liver diseases because it could mildly induce these cytokines.

Carcinoma, Hepatocellular↗
PubMed1996

Long-term administration of natural interferon-alpha in patients with chronic hepatitis C: relationship to serum RNA concentration, HCV-RNA genotypes, histological changes and hepatitis C virus.

To virologically assess the efficacy of interferon therapy in chronic hepatitis C, either 5 or 10 MU/day natural interferon-alpha (IFN alpha) was administered to 57 patients with chronic hepatitis C for 38 weeks. A complete and sustained response (CR-SR), as evidenced by the absence of serum hepatitis C virus (HCV)-RNA during the administration period and at 6 months after the final administration of IFN alpha and normal GPT level at 6 months after final administration, occurred in 42.6% (23/54) of subjects. Liver tissue was histologically evaluated using the histological activity index (HAI) score before and after the administration period. In CR-SR cases, significant improvements (P < 0.01) occurred in periportal necrosis, intralobular necrosis, portal inflammation and total score. A comparison, by HCV genotypes, revealed that CR-SR occurred in 60% (9/15) of subjects with type 2a and 30.3% (10/33) of subjects with type 1b. A comparison by virus concentration revealed that CR-SR occurred in 71.4% (15/21) of those subjects having a virus concentration of < 10(5) copies/mL, but in only 24.2% (8/33) of those having a virus concentration of > 10(5) copies/mL. Analysis by a multiple logistic model revealed a strong correlation between the therapeutic effect of interferon therapy and the pre-administration virus concentration (P = 0.0061) and genotype (P = 0.0015). These results suggest that the pre-administration virus concentration and genotype are both key factors affecting the therapeutic effect of interferon therapy in chronic hepatitis C and that the therapeutic effect of interferon is satisfactorily high, irrespective of virus concentration, in subjects with type 2a HCV, but varies depending on virus concentration in subjects with type 1b.

Aged↗
PubMed1996

[Tau protein in cerebrospinal fluid--a potential marker of Alzheimer's disease].

Levels of the microtubule-associated protein tau in cerebrospinal fluid (CSF-tau) were measured in samples from 87 patients with Alzheimer's disease (AD), 114 patients with non-AD neurological diseases, and 22 normal control subjects, by sandwich enzyme-linked immunosorbent assay. The CSF-tau level was significantly higher in patients with AD than in patients with non-AD neurological diseases and in controls. High CSF-tau levels were found irrespective of age at onset, apolipoprotein E genotype, clinical stage, and ethnic group. Western blots of AD CSF proteins revealed two to three immunoreactive bands with apparent molecular mass between 50 and 65 kDa, which is consistent with phosphorylated CSF-tau. These results suggest that CSF-tau reflects progressive accumulation of tau due to the progressive death of neurons in the AD brain. Assay of CSF-tau may prove to be a reliable diagnostic test for AD.

Aged↗
PubMed1996

Coexpression of cell-surface immunoglobulin (sIg), terminal deoxynucleotidyl transferase (TdT) and recombination activating gene 1 (RAG-1): two cases and derived cell lines.

While it is generally agreed that in the lymphoid differentiation of B lineage cells there is no stage in which cell-surface immunoglobulin (sIg) and terminal deoxynucleotidyl transferase (TdT) are expressed simultaneously, a few B cell acute lymphoblastic leukemia (B-ALL) cases with this phenotype have been reported. Two such cases and the derived cell lines are reported here, in which the expression of recombination activating gene-1 (RAG-1) was also detected. One case was a CD19+ CD22+ HLA-DR+ sIg+ (gamma, kappa) B-ALL. The cell line (Bay9I) also expressed CD10. Karyotypic analysis revealed t(14;18)(q32;q21) and additional aberrations. In the other case, the fresh leukemia cells expressed CD19, CD24 and HLA-DR antigen. The derived cell line (Tree92) also expressed CD22 and sIg (mu, lambda). The karyotype of the Tree92 cells was t(8;14)(q24;q32) with additional aberrations. Tree92 is the first established cell line having both t(8;14)(q24;q32) and TdT. TdT was detected by Northern blotting as well as indirect immunofluorescence analysis. In addition, both Bay9I and Tree92 expressed RAG-1, as detected by Northern blot analysis. Cross-linking of sIg on Tree92 cells with anti-mu antibody led to significant down-regulation of RAG-1 expression. It seems that there is a sIg+ TdT+ RAG-1+ B lineage differentiation stage, and that signaling through sIg can modulate RAG-1 expression.

Adult↗
PubMed1996

Sensitivity to dexamethasone and absence of bcl-2 protein in Burkitt's lymphoma cell line (Black93) derived from a patient with acute tumor lysis syndrome: comparative study with other BL and non-BL lines.

An Epstein-Barr virus (EBV)-negative Burkitt's lymphoma (BL) cell line, designated Black93, was established in culture from a patient who developed acute tumor lysis syndrome (ATLS). Growth inhibition in vitro by dexamethasone (DXM) and the expression of bcl-2 protein (Bcl-2) were investigated in Black93 and 17 other cell lines derived from EBV-negative or -positive BL, pre-B acute lymphoblastic leukemia (ALL), follicular lymphoma (FL), and EBV-positive lymphoblastoid cell lines of normal B cell origin (B-LCL), assuming an inherent susceptibility of Black93 to cell death. The most marked growth inhibition by DXM was observed in Black93, two other BL, two pre-B-ALL and two FL lines. The other cell lines were less sensitive or were resistant. DNA extracted from the Black93 cells treated with DXM showed a ladder of oligo-nucleosomal DNA on electrophoresis. On testing of fixed smears by indirect immunofluorescence, bcl-2 protein (Bcl-2) was undetectable in Black93 and three BL lines but was detected in all the other cell lines at varying intensity. Western blot analysis showed mostly the same results. In the BL lines, the most DXM-sensitive cell lines lacked Bcl-2 expression, and the DXM-resistant cell lines always expressed Bcl-2. While none of the DXM-resistant cell lines lacked Bcl-2 expression, several pre-B or FL lines that expressed [correction of expessed] Bcl-2 were sensitive to DXM. Black93 is the first reported cell line established from a patient with ATLS. The positive sensitivity to DXM and the lack of Bcl-2 expression observed in Black93 are a major characteristic exhibited frequently by BL lines and, probably, by fresh BL cells. These properties may contribute to the precipitation of ATLS.

Acute Disease↗
PubMed1995

Hepatocyte regeneration in chronic hepatitis C and interferon treatment: analysis of immunohistological identification of proliferating cell nuclear antigen (PCNA).

To evaluate the usefulness of proliferating cell nuclear antigen (PCNA) immunostaining in the assessment of the efficacy of interferon (IFN) therapy in chronic hepatitis C, we investigated the proliferative activity of hepatocytes in 67 patients with chronic hepatitis C, using this immunostaining method. The percentage of PCNA-positive hepatocytes was 2.4% in patients with chronic persistent hepatitis, 2.5% in those with chronic aggressive hepatitis 2A, and 3.9% in those with chronic aggressive hepatitis 2B. The PCNA count increased with the progression of the liver disease. Patients were classified as complete, partial, and non-responders to IFN; the percentage of PCNA-positive hepatocytes before IFN therapy was 1.6% in the complete responders, 3.9% in the partial responders, and 4.9% in the non-responders. There was a significant negative correlation between the percentage of PCNA-positive hepatocytes and the response to IFN treatment. Thirty-two of 53 cases (60.4%) in which the PCNA labeling index (LI) was less than 5.0 were complete responders compared with 13 of 14 cases (92.9%) in which the PCNA LI was higher than 5.0, representing partial responders or non-responders (P < 0.001). Most complete responders had a low PCNA LI, irrespective of HCV genotype. Our findings indicate that PCNA immunostaining is a simple and reliable index of cell proliferation in liver regeneration, and may be a useful predictor of the response to IFN treatment in chronic hepatitis C.

Adult↗
PubMed1995

Anaesthetic management for caesarean section in a patient with Kawasaki disease.

Kawasaki disease (KD) or mucocutaneous lymph node syndrome is an acute febrile illness affecting mainly children under four years of age. The most important clinical feature of this disease is coronary arteritis associated with aneurysms and thrombotic occlusions, which may lead to ischaemic heart disease or sudden death. It has now been more than 20 yr since its first description, and a number of survivors of childhood KD have reached child-bearing age. Despite the possible fatal outcome of this disease in adult patients with coronary artery manifestations, no information is available regarding the obstetrical anaesthetic management of patients with a history of KD. The purpose of this report is to describe the successful use of epidural anaesthesia in a patient with a history of KD undergoing Caesarean section and to discuss the anaesthetic considerations that should be given to adult survivors of childhood KD.

Adult↗
PubMed1995

Intrathecal prostaglandin E1 produces a long-lasting allodynic state.

The existence of prostaglandin (PG) receptors in the spinal cord has been demonstrated, but their role in sensory processing is not yet well defined. PGE1 is widely used clinically as a vasodilator. The present study was designed to investigate the effects of intrathecally administered PGE1 on the transmission of different types to sensory information, including that associated with noxious somatic, noxious visceral, and non-noxious somatic stimulation. The tail-flick (TF) test was employed to measure responses to noxious somatic stimuli, and the colorectal distension test was used to examine responses to noxious visceral stimuli. Withdrawal response to mechanical pressure produced by Semmes-Weinstein mono-filaments (SWMs) was measured as an assessment of sensitivity to non-noxious mechanical somatic stimulation. TF latencies and colorectal distension thresholds decreased for a short time (10-20 min) following the intrathecal (i.t.) administration of both 100 ng or 500 ng of PGE1. In sharp contrast to these short duration effects, there was a long-lasting increase in agitation scores (allodynia) produced by 3 different intensities of SWMs (0.217, 0.745 and 2.35 g) after administration of PGE1. The changes in agitation scores to SWMs were dependent on the dose of PGE1 and the intensity of stimulation. This increase of agitation score was seen when PGE1 was administered through the i.t. catheter or by direct i.t. puncture and the increase lasted for at least 2 days after drug administration. Intrathecal administration of saline, however, did not produce any changes in TF latencies, colorectal distension thresholds, or agitation scores produced by SWMs. No significant histological difference was seen between spinal cords exposed to 500 ng PGE1 and saline 48 h after drug administration. These results demonstrate that PGE1 may trigger a hypersensitive (allodynic and/or hyperalgesic) state in sensory processing pathways at the spinal level. They also indicate that long-lasting changes in processing of non-noxious, but not noxious, information produced by PGE1 continues after the disappearance of the direct action of PGE1.

Akathisia, Drug-Induced↗