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Biomedical subjects

S Kawano

Publications and source records attributed to S Kawano.

At least 325 records · Page 18Linked to original sources
PubMed1992

Prevalence of hepatitis C virus antibodies in hemodialysis patients and dialysis staff.

To estimate the prevalence of hepatitis C virus (HCV) infection in dialysis patients, serum anti-HCV antibodies were evaluated in 489 Japanese patients undergoing hemodialysis, and 152 members of the hospital dialysis staff by enzyme-linked immunosorbent assays for anti-C100, anti-KCL-163 (HCV nonstructural protein), and anti-JCC (translation product of the presumptive HCV core gene). Of the 489 hemodialysis patients, 100 (20.4%) were positive for anti-C100, 107 (21.9%) for anti-KCL-163, and 168 cases (34.4%) for anti-JCC. These rates were significantly higher than those for either the hospital staff or the healthy blood donors. Forty-two per cent of the dialysis patients were anti-HCV positive by at least one assay, suggesting that HCV infection is more common among this population than previously thought. Positivity for anti-HCV was related to the duration of hemodialysis. Elevated alanine aminotransferase levels were present in 12.5% of the dialysis patients, 77% of whom were also anti-HCV positive. The positivity rates among the 152 members of the hospital staff were 0.7% for anti-C100, 2.6% for anti-KCL-163, and 8.6% for anti-JCC, with the anti-JCC rate of positivity exceeding that of the healthy blood donors.

Adult↗
PubMed1992

[Cefepime (diHCl/L-arginine blend): intravenous continuous infusion and/or single dose subcutaneous toxicity study in rats and dogs].

To investigate single dose toxicity of cefepime (CFPM diHCl/L-arginine blend), the test drug was administered to rats [Crj: CD (SD)] of both sexes at dose levels of 500, 1,000 and 2,000 mg/kg using intravenous continuous infusion or subcutaneous injection, and to male beagle dogs at 1,000 and 2,000 mg/kg using intravenous continuous infusion. As the control, two additional groups of each animals were given either saline or L-arginine alone which was used in the test formulation to adjust pH values of CFPM diHCl solutions. The obtained results are summarized as follows: 1. Rats dosed with 2,000 mg/kg CFPM through intravenous continuous infusion showed slightly decreased spontaneous physical activity. One male rat dosed with L-arginine alone via continuous infusion also showed slightly decreased activity. Slight to severe inflammatory reactions at injection sites including sloughing of the tail were prominent at doses of 1,000 or 2,000 mg/kg of CFPM, or L-arginine alone. Average body weights of rats in the test groups of either sex were comparable to the controls in all of the dose groups of the same sex during the 14-day test period. 2. Rats receiving 2,000 mg/kg CFPM in single subcutaneous injection showed slightly diminished activities. Slight to moderate reactions occurred around the injection site (viz., hardening, depilation, scab-formation and necrosis) in rats injected any of the 3 doses of CFPM. Though body weight gains were slightly retarded in male rats receiving 2,000 mg/kg CFPM during the last half of the observation period, such weight gain retardation was not observed in rats of other dose groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Cefepime (BMY-28142 diHCl/L-arginine blend): one-month repeated dose subcutaneous toxicity study in rats].

In order to investigate the toxicity of cefepime (CFPM, BMY-28142 diHCl/L-arginine blend upon repeated subcutaneous dosing), the test article was administered to Crj:CD(SD) rats of both sexes at daily dose levels of 150 (low dose), 500 (intermediate dose) and 1,500 (high dose) mg/kg/day by subcutaneous route for 28 days. Two additional groups of rats were given either saline (negative control) or L-arginine (vehicle control). Doses were equally divided and administered twice each day with an interval of approximately 5 hours between the 2 doses of a same day. A half of rats in negative control and high dose groups were retained for examination during one-month recovery period. The results obtained are summarized as follows: 1. Upon general observations, it was found that drug-related changes were restricted to the injection sites. Depilation and scab-formation of the injection sites were noted in high dose rats of both sexes and intermediate dose females. No deaths occurred during the study. 2. Slightly depressed body weight gains were observed for high dose males during the latter part of the dosing period. 3. Slightly lower food consumptions were noted for intermediate and high dose males at Week 1. 4. Slightly higher water consumptions were generally detected for high dose rats during the dosing period. 5. Hematological examinations revealed that a slight decrease in the average value of relative lymphocyte counts and a slight increase in the average value of relative segmented neutrophil counts were evident for high dose males. These findings might be attributable to the inflammatory reactions at the injection sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Reproductive and developmental toxicity studies on cefepime dihydrochloride administered subcutaneously to rats during the premating, gestation and lactation periods].

Cefepime dihydrochloride (CFPM) was administered subcutaneously daily at doses of 0, 150, 500 and 1,000 mg/kg for 63 days prior to mating and during mating to male Crj: CD (SD) rats and for 14 days prior to mating and during mating, as well as periods of gestation and lactation to female SD rats. Saline and L-arginine hydrochloride (L-arginine) were used as control articles. Daily doses of test and control articles were equally divided and administered twice a day (b.i.d.). The results obtained are summarized as follows: 1. Soft stool was observed for both male and female F0 rats at CFPM 1,000 mg/kg at the first week of administration period. Further, depilation of injection sites was found in 7 males and 12 females at the same dose level. 2. Body weight gains were suppressed in male F0 rats from Day 28 to 63 of administration period at CFPM 1,000 mg/kg. Moreover, food consumption was reduced in F0 female rats during the first week of administration period at all dose levels of CFPM. 3. CFPM failed to affect the reproductive performance in both male and female F0 rats. 4. Kidney weights were increased in both male and female F0 rats and adrenal weights were augmented in male F0 rats at CFPM 1,000 mg/kg. On the other hand, cecal enlargement were observed for F0 dams treated with CFPM. However, these changes were not considered to be unique to this drug, because they have been described with most antibiotics in this species and appears to be results of modifications in gut flora. 5. Prenatal developments in F1 fetuses were not affected by CFPM. 6. CFPM failed to affect delivery status of F0 dams or survival and lactation indices in F1 pups. 7. CFPM did not affect postnatal differentiations, developmental behaviors, learning ability and memory, spontaneous motor activity or emotionality in F1 rats. 8. Body weight gains and food consumption in both male and female F1 rats were not affected by CFPM. 9. CFPM did not alter the organ weights in both male and female F1 rats. 10. There were no significant differences between drug treated animals and controls regarding the reproductive performance and delivery status of F1 rats. 11. Influences on survival indices, body weights and organ weights were not apparently observed for F2 pups even at CFPM 1,000 mg/kg. Based on the reproductive and developmental indices, the no-effect dose level of CFPM under the present experimental condition was estimated to be 1,000 mg/kg/day against dams (F0) and their offspring (F1).

Animals↗
PubMed1992

Two cases of accidental transmission of hepatitis C to medical staff.

Two medical doctors (a 38-year-old male and a 25-year-old female) were admitted to our department with jaundice. They had injured themselves with, respectively, a scalpel and a needle contaminated with anti-hepatitis C virus antibody-positive blood, at 2 and 1.5 months, respectively, prior to admission. They were both suffering from clinically typical acute hepatitis. The polymerase chain reaction showed that hepatitis C RNA and anti-hepatitis C virus antibody were transiently positive in the male doctor, while serum transaminase levels were transiently abnormal. In the female doctor, hepatitis C RNA was initially negative, but became strongly positive, and abnormal serum transaminase levels persisted. Interferon therapy resulted in the hepatitis C RNA's becoming negative again, and the transaminase levels returned to normal. The clinical and other findings strongly suggested that in both patients hepatitis C developed as a result of the respective in-hospital accidents.

Accidents, Occupational↗
PubMed1991

Ethanol-induced disturbance of hepatic microcirculation and hepatic hypoxia.

The hypothesis was tested whether ingestion of ethanol might disturb the hepatic microcirculation with resulting hepatic hypoxia. Infusion of ethanol increased the portal pressure concentration-dependently in rat livers perfused with Krebs-Henseleit buffer at a constant flow rate (Emax = 11.5 cm H2O, EC50 = 90 mM). This increase in portal pressure was due to hepatic vasoconstriction, since it diminished in the presence of sodium nitroprusside, a direct acting vasodilator. The regional hepatic tissue hemoglobin concentration after perfusion with added erythrocyte suspension (hematocrit 1%), measured by tissue-reflectance spectrophotometry, was significantly diminished by the infusion of ethanol, indicating the impairment of the microcirculation of the superficial layer of the liver. When the absorption spectrum of the liver was examined by reflectance spectrophotometry, infusion of ethanol caused a parallel reduction of all the mitochondrial respiratory cytochromes in a concentration-dependent fashion, concomitant with the increase of portal pressure, indicating a marked reduction of oxygen concentration in superficial liver tissue. The reduction of the respiratory cytochromes was also associated with the decrease in oxygen consumption of the liver, indicating that the hepatic hypoxia was due to the reduction of oxygen delivery to hepatocytes rather than the increased oxygen consumption of the liver. The reduction of the respiratory cytochromes was correlated with the increase in portal pressure and was inhibited by sodium nitroprusside. These data indicate that the ethanol-induced hepatic vasoconstriction disturbs hepatic microcirculation, resulting in hepatic hypoxia and reduction of mitochondrial respiratory cytochromes.

Animals↗
PubMed1991

Chronic effect of intragastric ammonia on gastric mucosal structures in rats.

The prevalence of Helicobacter pylori (HP) in the gastric mucosa of patients with chronic atrophic gastritis has been reported to be significantly higher than in normal mucosa. To clarify the role of HP in the etiology of chronic atrophic gastritis, we assessed the effect of ammonia on the gastric mucosal structure in rats, since HP has a strong urease activity and produces abundant amounts of ammonia. Ammonia administered orally at 0.01% and 0.1% as drinking water for two to four weeks decreased the mucosal thickness and the parietal cell number and oxyntic gland number in a dose- and time-dependent manner. The decrease of mucosal thickness was significantly greater in the antral mucosa than in the body mucosa. The border between the antral and body mucosa shifted toward the cardia, reflecting the decrease in oxyntic gland numbers. Furthermore, intracellular mucin was also decreased in a dose- and time-dependent manner, especially in the antral mucosa. Thus, ammonia chronically administered orally in rats led to changes in gastric mucosal structures and functions. The results suggest that the ammonia produced by HP partly plays an etiologic role in chronic atrophic gastritis.

Administration, Oral↗
PubMed1991

Developmental changes in the calcium currents in embryonic chick ventricular myocytes.

Using the patch-clamp technique, we recorded whole-cell calcium current from isolated cardiac myocytes dissociated from the apical ventricles of 7-day and 14-day chick embryos. In 70% of 14-day cells after 24 hr in culture, two component currents could be separated from total ICa activated from a holding potential (Vh) of -80 mV. L-type current (IL) was activated by depolarizing steps from Vh -30 or -40 mV. The difference current (IT) was obtained by subtracting IL from ICa. IT could also be distinguished pharmacologically from IL in these cells. IT was selectively blocked by 40-160 microM Ni2+, whereas IL was suppressed by 1 microM D600 or 2 microM nifedipine. The Ni2(+)-resistant and D600-resistant currents had activation thresholds and peak voltages that were near those of IT and IL defined by voltage threshold, and resembled those in adult mammalian heart. In 7-day cells, IT and IL could be distinguished by voltage threshold in 45% (S cells), while an additional 45% of 7-day cells were nonseparable (NS) by activation voltage threshold. Nonetheless, in most NS cells, ICa was partly blocked by Ni2+ and by D600 given separately, and the effects were additive when these agents were given together. Differences among the cells in the ability to separate IT and IL by voltage threshold resulted largely from differences in the position of the steady-state inactivation and activation curves along the voltage axis. In all cells at both ages in which the steady-state inactivation relation was determined with a double-pulse protocol, the half-inactivation potential (V1/2) of the Ni2(+)-resistant current IL averaged -18 mV. In contrast, V1/2 of the Ni2(+)-sensitive IT was -60 mV in 14-day cells, -52 mV in 7-day S cells, and -43 mV in 7-day NS cells. The half-activation potential was near -2 mV for IL at both ages, but that of IT was -38 mV in 14-day and -29 mV in 7-day cells. Maximal current density was highly variable from cell to cell, but showed no systematic differences between 7-day and 14-day cells. These results indicate that the main developmental change that occurs in the components of ICa is a negative shift with embryonic age in the activation and inactivation relationships of IT along the voltage axis.

Action Potentials↗
PubMed1991

Effect of ethanol on endothelin-1 release from gastric vasculature.

The effects of ethanol on gastric vasculature in isolated vascularly perfused rabbit stomach was investigated. The isolated stomach was perfused with Krebs-Henseleit solution containing 3% dextran bubbled with 95% O2 and 5% CO2 at a rate of 12 ml/min. After mixture and perfusion of 10 mM to 400 mM of ethanol, perfusion pressure and endothelin-1 concentration in effluent from gastric vasculature were measured. Perfusion pressure and endothelin-1 concentration in effluent increased in a dose-dependent manner with increasing ethanol concentrations. In conclusion, the data suggest that ethanol may stimulate the release of endothelin from gastric vasculature and may cause gastric ischemia due to vasoconstriction resulting in acute gastric mucosal injury.

Animals↗
PubMed1991

The prevalence of anti-HCV antibodies in hemodialysis patients.

The prevalence of antibodies to hepatitis C virus (anti-HCV) was assessed in 489 hemodialysis patients and 152 members of the staff of dialysis units, using an Ortho HCV Ab ELISA Test. Of the 489 patients, 100 (20.4%) had anti-HCV, a significantly greater rate than was found in either staff members (0.7%, P less than 0.01) or local healthy blood donors (1.1%, P less than 0.001). Anti-HCV positivity was apparently related to the duration of hemodialysis.

Adult↗
PubMed1991

Evaluation of the KCL-163 ELISA test for detecting antibodies against hepatitis C virus in patients with non-A, non-B chronic hepatitis.

A specific ELISA test (KCL-163) for detecting anti-hepatitis C virus antibody (anti-HCV) has been developed (Kaketsuken). Using the KCL-163, 183 serum samples obtained from patients with non-A, non-B hepatitis (NANBH) were examined. We also tested and compared results with Ortho HCV ELISA (C100) and C825 ELISA. Of these 183 samples, 139 (76%), 121 (66%), and 88 (48%) were positive with KCL-163, C100 and C825, respectively. These results showed that there were patients with NANBH caused by HCV who were seronegative in C100 ELISA. KCL-163 ELISA is applicable for the diagnosis of HCV infection in these patients.

Chronic Disease↗
PubMed1991

Detection of antibodies to hepatitis C virus (anti-HCV) in patients with various liver diseases, by an ELISA (KCL-163) test consisting of synthetic peptides corresponding to an HCV genome.

In 1989, the Chiron group developed an enzyme immunoassay system (C100) for detecting antibodies to hepatitis C virus (anti-HCV). In our examinations, the positive rate was 65.3% of the total number of patients (199) with non-A, non-B (NANB) liver disease. Additionally, a specific ELISA system (KCL-163) was developed by Kaketsuken (Kumamoto, Japan) based on synthetic peptides corresponding to an HCV genome of a Japanese isolate. In this study, we measured antibodies to HCV by KCL-163, and compared the results of KCL-163 with that of C100 in patients with various liver diseases. Our emphasis was on the discrepancies between the results of the two types of ELISA. We concluded that it was not sufficient to diagnose hepatitis C only by assay systems based on the C100-3 region of an HCV genome, and that KCL-163 was superior to C100 in its specificity and sensitivity in the diagnosis of hepatitis C.

Enzyme-Linked Immunosorbent Assay↗
PubMed1991

Transient outward currents and action potential alterations in rabbit ventricular myocytes.

To clarify ionic mechanisms underlying successive changes in action potential repolarization upon sudden increase in driving rate or initiation of rapid drive after a rest, membrane potentials and currents were recorded from isolated rabbit ventricular myocytes using the suction-pipette whole-cell clamp method. When 20 action potentials were elicited with a stimulus frequency of 2.0 Hz after a rest period of 20 s, the plateau and action potential duration showed complex changes in successive beats, whereas they were nearly constant with stimulation at 0.1 Hz. There were only weak correlations between changes in action potential parameters and preceding diastolic intervals. The changes were prominent in the first 10 beats but subsided gradually thereafter, attaining nearly steady configurations of action potentials. When depolarizing pulses were applied at a fast rate, under the voltage clamp, the amplitudes of the initial inward current in the presence of tetrodotoxin changed greatly depending on the pulse numbers and diastolic intervals, whereas the delayed outward K+ current changed little. Variations of the initial inward current in successive pulses were caused by different degrees of activation and recovery from inactivation in the Ca2+ current, the Ca(2+)-sensitive and -insensitive transient outward current. While inhibition of either one or two current components decreased the action potential alterations, blocking the three components completely abolished them. These results indicate that alterations of the Ca(2+)-sensitive and -insensitive transient outward current together with the Ca2+ current contribute to the action potential alterations after initiation of rapid drive or an increase in driving rates.

Action Potentials↗
PubMed1991

Comparison of cytochrome P-450 species which catalyze the hydroxylations of the aromatic ring of estradiol and estradiol 17-sulfate.

For identification of microsomal cytochrome P-450 (P-450) enzymes which catalyze 2- or 4-hydroxylations of estrogens in the rat liver, estradiol (E2) and estradiol 17-sulfate (E2-17-S) were selected as the substrates and incubated with various kinds of purified P-450 enzymes: PB-1, PB-2, PB-4 and PB-5 obtained from phenobarbital-treated male rats (Sprague-Dawley); MC-1 and MC-5 from 3-methylcholanthrene-treated male rats; and UT-1, UT-2, UT-4 and UT-5 from untreated animals. The reactions were carried out under the P-450-reconstructed system, and the resulting products were determined by HPLC using electrochemical detection. All the enzymes tested were shown to have varying degrees of catalytic activities for 2-hydroxylation of the two substrates; UT-1 and UT-2 had the highest activity. Of the induced P-450 enzymes, PB-2 and MC-1 showed fairly high catalytic activity for 4-hydroxylation of E2. The P-450 enzymes obtained from the untreated male rats, especially UT-4, showed the highest catalytic activity for 4-hydroxylation of the two substrates. From these results and also from kinetic experiments, the P-450 enzymes which catalyze 2- and 4-hydroxylations of estrogen were considered to be different species. A part of E2 was converted to such metabolites as estrone and those having a hydroxyl group at positions 6 beta, 15 alpha or 16 alpha, each production of which was estimated to be catalyzed by single or multiple P-450s.

Animals↗
PubMed1991

Two-dimensional computer color graphics of gastric mucosal blood distribution in normal subjects and ulcer patients.

The mucosal blood volume in 20 to 24 different regions of stomach was estimated by reflectance spectrophotometry during endoscopy, and an image showing mucosal blood distribution was made by two-dimensional computer color graphics with the aid of a personal computer. In 55 normal controls, the estimated mucosal blood volume (EMBV) was greater in the corpus mucosa than in the antral mucosa, and less in the lesser curvature than in the greater curvature. The volume in the anterior and posterior walls was almost the same. In 15 patients with active gastric ulcers in the angular region, the EMBV was decreased in all regions in the stomach. In 37 patients with healing ulcers, the EMBV increased, resuming the same levels as in normal controls. However, the EMBV around the ulcer increased remarkably at this stage. In 35 patients with ulcers in the scarring stage, the distribution of the EMBV was similar to that in the normal controls. These hemodynamic changes were shown clearly in a color display with the aid of a personal computer. This method could offer new possibilities in endoscopic research.

Adult↗
PubMed1991

Analysis of mucosal blood hemoglobin distribution in gastric ulcers by computerized color display on electronic endoscopy.

A technique of computerized color display was used to analyze the mucosal blood hemoglobin distribution in patients with gastric ulcers. Using an electronic endoscope, red and green images (Vr and Vg) obtained separately from the electronic endoscopic image were transferred to an image analyzer and a computer. The mucosal hemoglobin content was calculated at each pixel of the image using the formula: index of hemoglobin content = 32[log2(Vr/Vg)]. Forty endoscopy examinations were performed in 15 patients with small ulcers (less than or equal to 1 cm) in the gastric angle and 5 normal subjects. The index of hemoglobin content ranged from 24 to 40 in the normal subjects. The index for the area around an active ulcer was mostly below 33. In cases of ulcers in the healing stage it increased to more than 40. The index was still above 40 in ulcer scars in the S1 stage, but within normal range in most of the mucosa in the S2 stage. Thus, the mucosal blood hemoglobin distribution can be assessed by computerized color analysis in patients with gastric ulcers at various stages.

Data Display↗