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Biomedical subjects

O Inoue

Publications and source records attributed to O Inoue.

At least 55 records · Page 3Linked to original sources

Long-term evolution of fibrosis from chronic hepatitis to cirrhosis in patients with hepatitis C: morphometric analysis of repeated biopsies.

To clarify the characteristics of fibrosis developed in the process from chronic hepatitis C to cirrhosis, a morphometric analysis of liver biopsy samples was conducted on 25 chronic hepatitis C patients and 20 chronic hepatitis B patients (controls). Hepatitis C patients were followed up for 3 to 23 years. The mean number of liver biopsies performed on these patients was 3.8. Each biopsy was evaluated for the degree of fibrosis by using two methods: a semiquantitative method with a staging scoring system, and morphometry using a computed image analysis system. A significant correlation was observed between the Stage and the area of fibrosis (AF = the ratio of the area of fibrosis to that of the entire tissue specimen). The AF in cirrhosis was significantly higher in hepatitis C patients than in hepatitis B patients. The ratio of AF in the last biopsy sample to AF in the initial biopsy sample was significantly higher in hepatitis C patients than in hepatitis B patients. Evolution from chronic hepatitis C to cirrhosis occurred more frequently in patients aged > or = 50 years, and this time period was 1.8 times shorter than that in patients aged < 50 years. AF in the initial biopsy related significantly to the period of evolution from chronic hepatitis C to cirrhosis. AF in the initial biopsy might be a predictive factor for prognosis.

Adult↗

Enhancement of [123I]beta-CIT binding in the striatum with clomipramine: is there a serotonin-dopamine interaction?

Many reports support the concept of serotonergic-dopaminergic interaction in the brain. However, at present, there are few methods to study this relationship in vivo. The purpose of this study was to investigate the effect of serotonin (5-HT) uptake inhibitor, clomipramine, on a dopamine (DA) transporter ligand, [123I]beta-CIT (RTI-55), in rat brain. Dose-dependent changes in [123I]beta-CIT specific binding induced by clomipramine were studied in the striatum (rich in DA transporter) and the hypothalamus (rich in 5-HT transporter). The changes in the time-activity curves of [123I]beta-CIT specific binding after clomipramine injection were also examined in these two regions. Using the cerebellum as the reference region, k3 and k4 values with and without clomipramine administration were estimated by a two-compartment kinetic analysis. Clomipramine inhibited [123I]beta-CIT specific binding in the hypothalamus, but enhanced its specific binding in the striatum in a dose-dependent manner. Kinetic analysis showed that k3 in the striatum was increased by 55%. In conclusion, enhancement of [123I]beta-CIT binding in the striatum after clomipramine administration indicated the possibility of 5-HT-DA interaction.

Animals↗

Quantitative analysis of interferon alpha/beta receptor mRNA in the liver of patients with chronic hepatitis C: correlation with serum hepatitis C virus-RNA levels and response to treatment with interferon.

We analysed the expression of interferon (IFN) alpha/beta receptor mRNA in the liver of patients with chronic hepatitis C and examined the relationship between the expression of this receptor gene and the level of hepatitis C virus (HCV)-RNA as well as the response to 16 weeks of 6 x 10(6) units IFN. The mean level of IFN alpha/beta receptor mRNA in patients with chronic HCV infection (expressed as delta cycle; 10.8 +/- 1.9 (mean +/- SD); n = 39) was significantly higher than that of control subjects (9.4 +/- 0.5; n = 6; P < 0.01). There was a significant negative correlation between the level of IFN alpha/beta receptor mRNA and serum HCV-RNA in 39 patients with chronic hepatitis C (R = -0.546; P < 0.01). The mean level of IFN alpha/beta receptor mRNA in six patients who showed a complete response to IFN therapy (12.3 +/- 1.6) was higher than that of 15 patients who failed to respond to therapy (10.1 +/- 1.5; P < 0.01). Our results are consistent with the suggestion that the anti-viral activity of IFN depends on the level of the IFN alpha/beta receptor on hepatocytes in patients with chronic hepatitis C.

Adult↗

Duration of chronic HCV infection and efficacy of interferon in chronic hepatitis C patients with a history of blood transfusion. The Study Group for Treatment of Hepatitis in the Kyushu Area.

To investigate correlations between the interval between blood transfusion and the start of IFN therapy, and IFN efficacy, we studied chronic hepatitis C patients with a history of blood transfusion. The subjects were 122 patients with chronic hepatitis C and a history of blood transfusion at 64 institutions. The patients were treated with high or low-dose IFN. High-dose therapy consisted of intramuscular injection of human lymphoblastoid interferon (HLBI), 6 x 10(6) IU daily for 2 weeks, then 3 times a week for 22 weeks, and low-dose interferon therapy of intramuscular injection of HLBI, 6 x 10(6) IU daily for 2 weeks, then 3 x 10(6) IU 3 times a week for 22 weeks. Normal serum ALT levels for 6 months or more after completing IFN (complete response) were found in 44/122 (36.2%) patients and HCV RNA was no longer detectable after completing IFN therapy in 19/68 (27.9%). Patients in whom the interval between blood transfusion and the start of IFN therapy was less than 20 years had significantly higher rates of HCV RNA-negative complete response than those in whom the interval was 20 years or more (p < 0.039). When chronic HCV infection is caused by blood transfusion, the efficacy of IFN depends on the duration of chronic HCV infection. Since the duration of HCV infection is a factor in predicting efficacy, early IFN therapy may be more effective.

Adult↗

[Diagnostic criteria for Non-ABCDE hepatitis].

Hepatitis viruses A, B, C, D and E are all well-characterized, molecularly defined agents with unequivocal disease association. Usual diagnosis for these virus infections are established by serological markers which are specific antigens or antibodies for these virus infections. But serological diagnosis occasionally shows pseudonegative results because this method is indirect diagnosis. In contrast, molecular diagnosis catches directly components of viral structure. Molecular diagnosis is also able to show the appearance and disappearance of these hepatitis viruses. Diagnostic criteria for Non-ABCDE hepatitis is the exclusion of hepatitis viruses A, B, C, D and E infections by using not only serological diagnosis but also molecular diagnosis.

Acute Disease↗

A subclass of GABAA/benzodiazepine receptor exclusively localized in the limbic system.

An in vivo saturation study using 11C-labelled Ro15-4513 with high specific radioactivity (> 70 GBq mumol-1) revealed the presence of very high-affinity and high-affinity binding sites (Kd values in the amygdala approximately 0.4 and 18.7 nM, respectively) in the gamma-aminobutyric acid type A/benzodiazepine (GABAA/BZ) receptor in the living monkey brain. Subtraction of an image obtained using [11C]Ro15-4513 with low specific radioactivity from an image obtained by that with high specific radioactivity, both of which were scanned with a high spatial resolution positron emission tomography camera, demonstrated that the very high-affinity sites are exclusively localized in the limbic system, such as in the amygdala, hippocampus, anterior cingulate, septum, nucleus accumbens and insular cortex. The localization of the very high-affinity binding sites, which may be derived from a subclass of central GABAA/BZ receptors, might account for the anxiolytic effect of BZ analogues.

Affinity Labels↗

Serum concentrations of total bile acids in patients with acute Kawasaki syndrome.

OBJECTIVES: To investigate serum concentrations of total bile acids (TBAs) in patients with acute Kawasaki syndrome (KS) and correlate those concentrations with other liver function test results. PATIENTS AND METHODS: Seventy-one Japanese patients with KS (mean age, 1.6 years). Blood samples from 29 patients were obtained during the acute and convalescent phases of KS. RESULTS: Elevated serum TBA concentrations higher than 20 micromol/L were detected in 16 (22.5%) of the patients with acute KS. Serum concentrations of TBAs gradually returned to normal (P=.001, Pearson's correlation coefficient). The mean +/- SD serum concentration of TBAs of patients during the acute phase (37.9 +/- 63.9 micromol/L) was significantly higher than that of patients during the convalescent phase (7.2 +/- 7.5 micromol/L) (P=.02, Pearson's correlation coefficient). The data show a correlation between the serum concentrations of TBAs with those of alanine aminotransferase (P=.03, Pearson's correlation coefficient), total bilirubin (P<.001, Pearson's correlation coefficient), and C-reactive protein (P=.01, Pearson's correlation coefficient) measured during the acute phase. CONCLUSIONS: The cause of the elevated concentration of serum TBAs in patients with acute KS is unclear. Increased bile acid synthesis from cholesterol may occur, or patients with acute KS may suffer from damage to the bile duct cells of their biliary systems caused by cytokine activation. This damage may depress bile acid excretion, thereby increasing the serum concentrations of TBAs.

Acute Disease↗

The long-term pathological evolution of chronic hepatitis C.

Most patients infected with hepatitis C virus (HCV) develop chronic hepatitis. Unfortunately, the pathological evolution of this disease over time is not completely understood. We studied 70 HCV-positive patients, from whom 2 to 10 liver biopsy specimens (mean, 3.9) had been obtained during an interval of 1 to 26 years (mean, 8.8 years). Each biopsy specimen was evaluated independently by four pathologists who each provided a numerical score for the grade of portal/periportal necroinflammation (0-4), grade of lobular necroinflammation (0-4), their sum (final grade), and the stage of fibrosis (1-4). The scores were correlated with progression of disease, if any, and transition to cirrhosis. During follow-up, 35 patients (50%) developed cirrhosis. Cirrhosis developed in all patients with a high final grade (> or = 5) of necroinflammation on initial biopsy who were followed for 10 years and in 96% of patients with an intermediate final grade (3.5-4.9) who were followed for 17 years. Only 30.4% of patients with low final grade (< or = 3.4) on initial biopsy developed cirrhosis after 13 years. All patients with evidence of septal fibrosis with incomplete nodularity (stage 3.0-3.4) in the initial biopsy progressed to unequivocal cirrhosis by 10 years. The rate of progression to cirrhosis was accelerated in patients whose initial biopsies showed high-grade and -stage lesions. This study demonstrates the importance of grading and staging liver biopsy lesions in chronic hepatitis C, particularly for patients with high-grade necroinflammation, septal fibrosis, and regions of modularity on initial biopsy who are at high risk of developing advanced cirrhosis in the ensuing decade.

Biopsy↗

Differential kinetics of [123I]beta-CIT binding to dopamine and serotonin transporters.

Iodine-123-labelled 3beta-(4-iodophenyl)tropane-2beta-carboxylic acid ([123I]beta-CIT) labels both the dopamine transporter (DAT) and the serotonin transporter (5-HTT) and this ligand is able to clarify pathological changes in both dopaminergic and serotonergic systems. However, the differential kinetics of beta-CIT binding to DAT and 5-HTT has not been clarified fully. In this study we examined time-activity curves of [123I]beta-CIT in individual regions in the rat brain. Using cerebellum as the reference region, k3 and k4 values were estimated by a two-compartment kinetic analysis. In the striatum, the kinetics was slowest among all brain areas. In this area specific binding reached its peak 4 h after the injection. In the hypothalamus, specific binding reached its peak 1 h after the injection and its amount did not change until 4 h after the injection. In the occipital cortex, the binding and washout of the ligand were fastest among all brain regions. Estimated k3 values were 0.040+/-0.003 in the striatum, 0.019+/-0.002 in the hypothalamus and 0.082+/-0.011 in the occipital cortex (min-1, mean +/-SD). Estimated k4 values were 0.0034+/-0.0005 in the striatum, 0.0071+/-0.0009 in the hypothalamus and 0.083+/-0.013 in the occipital cortex (min-1, mean +/-SD). Therefore binding kinetics of [123i]beta-cit in the region rich in dat is apparently different from that in the region rich in 5-HTT. These results will provide fundamental data to image both DAT and 5-HTT in one series of examinations with [123I]beta-CIT.

Animals↗

[Antinociceptive effects of Kami-kihi-to in mice].

Oral administration of Kami-kihi-to (KMK) dose-dependently inhibited the response to acetic acid-induced writhing in mice. The KMK-induced antinociceptive action was reduced by pretreatment with yohimbine, an alpha 2-adrenergic antagonist, or cyproheptadine, a serotonergic antagonist, but not naloxone, an opiate antagonist. The antinociceptive action of KMK was clearly reduced by pretreatment with alpha-methyl-DL-p-tyrosine, reserpine or p-chlorophenylalanine or by simultaneous treatment with diethyldithiocarbamate, all of which are monoamine synthetic inhibitors or monoamine depletors. After spinal transection, the antinociceptive effect of KMK was markedly reduced. These findings suggest that the antinociceptive action of KMK may be related to pain inhibitory systems such as the serotonergic and noradrenergic systems at the supraspinal level.

Adrenergic alpha-Antagonists↗

Subtle increase in leukocyte counts in association with drinking and smoking habits.

Peripheral leukocyte counts were examined in venous blood of more than 800 male workers exposed to toluene, xylenes, a combination of the two, or neither. Information on the social habits of smoking and drinking was obtained in an occupational health interview. The analysis showed that smoking (15 cigarettes/day on average) induced a significant increase (by 7%) in leukocyte counts, and that an additional increase was induced when the drinking habit was coupled with smoking. Drinking alone tended to increase the leukocyte counts but the effect was statistically nonsignificant, possibly because the number of nondrinking smokers was limited. The study stresses the importance of paying attention to smoking and drinking habits when evaluating hematological parameters such as peripheral leukocyte counts in solvent-exposed workers.

Adolescent↗

Difference in response of D2 receptor binding between 11C-N-methylspiperone and 11C-raclopride against anesthetics in rhesus monkey brain.

The effects of anesthesia on dopamine D2 receptor binding in the rhesus monkey brain were examined using positron emission tomography. The bindings of 11C-N-methylspiperone (NMSP) and 11C-raclopride (RAC) were measured under controlled ketamine or isoflurane anesthesia. The binding of 11C-NMSP was significantly lower in the striatum anesthetized with isoflurane than with ketamine. There was a smaller change in the binding of 11C-RAC than of 11C-NMSP. These findings suggest that changes in 11C-NMSP or 11C-RAC binding induced by anesthetics were not due solely to changes in the competition of endogenous dopamine.

Anesthetics↗

Hypersensitivity of cortical muscarinic receptors in Parkinson's disease demonstrated by PET.

The status of muscarinic receptors (mAChRs) is not clear in Parkinson's disease (PD). We measured mAChR binding in the brain of eight patients with PD and eight, age-matched, healthy controls by positron emission tomography (PET) and [11C]N-methyl-4-piperidyl benzilate ([11C]NMPB). PD patients were not demented according to DSM III criteria but showed significant frontal lobe dysfunction in the Modified Wisconsin Card Sorting Test. A mean K3 value, which is an index of mAChR binding calculated by a graphical method, was 20% higher in the frontal cortex of PD patients than controls (p < 0.05). Hypersensitivity of mAChRs in the frontal cortex of PD patients may be a response to a loss of ascending cholinergic input to that region, and may relate to frontal lobe dysfunction in PD.

Aged↗

Urinary Phenylglyoxylic Acid Excretion after Exposure to Ethylbenzene among Solvent-exposed Chinese Workers.

Factory surveys were conducted in the second half of work weeks on 360 solvent workers (202 men and 158 women) and 281 controls in China. Monitoring personal exposures showed that ethylbenzene exposure was low (geometric mean 1.8 ppm) and was accompanied by coexposure to toluene (1.5 ppm) and three xylene isomers (6.7 ppm). Urine samples collected at the end of the eight-hour shift were analyzed for phenylglyoxylic and mandelic acids by high-pressure liquid chromatography at 257 nm. Despite the low level of the exposures, a significant correlation was observed between ethylbenzene exposure and urinary phenylglyoxylic acid, with high (0.6-0.7) correlation coefficients, suggesting that urinary phenylglyoxylic acid is a good marker of occupational exposure to ethylbenzene. Mandelic acid also correlated with ethylbenzene exposure, but with much smaller coefficients (0.2), possibly because the method employed was more sensitive to phenylglyoxylic acid than to mandelic acid.

Journal Article↗

Upper-extremity Musculoskeletal Disorders in Keyboard Operators in Brazil: A Cross-sectional Study.

This study sought to determine the prevalence of upper-extremity musculoskeletal disorders (UEMSDs) among keyboard operators in Sao Paulo, Brazil, and to compare this prevalence with that among other office workers. One hundred and thirty keyboard operators (mean age 33 years, 60 male/70 female) and 138 office workers (mean age 35 years, 82 male/56 female) from two computing centers were interviewed by a research assistant using a standardized questionnaire. Symptomatic subjects, defined as those who reported upper extremity pain or lost work time due to pain in the preceding 12 months, were examined by a rheumatologist. Mean (SD) lengths of employment were 9 (6) years for keyboard operators and 8 (6) years for office workers. Upper-extremity pain during the preceding seven days was reported by 66 keyboard operators (51%) and by 18 office workers (13%) (p < 0.0001); during the preceding 12 months, by 90 keyboard operators (69%) and by 26 office workers (19%) (p < 0.0001). UEMSDs were diagnosed following physical examination in 50 keyboard operators and in 12 office workers (9%) (p < 0.0001). Tenosynovitis was the most common disorder diagnosed among the keyboard operators (n = 23). Among the keyboard operators the prevalence of UEMSDs was significantly lower for males (p = 0.017, OR = 0.38, 95%CI = 0.17-0.86). The presence of a diagnosed UEMSD was significantly associated with duration of employment (p = 0.005) and lack of or insufficient rest breaks (p = 0.012). Keyboard operators had significantly more UEMSDs than did office workers. Strategies aimed at the reduction of repetitive strain injuries among keyboard operators, such as the provision of adequate work breaks, should be evaluated.

Journal Article↗