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Biomedical subjects

T Kamada

Publications and source records attributed to T Kamada.

At least 289 records · Page 16Linked to original sources
PubMed1994

Serial quantitative analysis of serum hepatitis C virus RNA level in patients with acute and chronic hepatitis C.

To examine changes in the serum level of hepatitis C virus RNA in acute and chronic phases of hepatitis C virus infection, we tested serial serum samples of six patients with acute hepatitis C (posttransfusion: three; sporadic: three) and 11 patients with chronic hepatitis C using a competitive reverse transcription and polymerase chain reaction assay. The internal standard consisted of known amounts of synthetic mutated RNA. No patient with acute hepatitis showed resolution during the follow-up period (24-57 weeks). In posttransfusion cases, titers of hepatitis C virus RNA (log10[hepatitis C virus RNA copies/ml serum]) rose to a high level (7.5-9.5) in the early phase of infection (4-12 weeks after the transfusions) in association with the first serum alanine aminotransferase peaks. Titers of hepatitis C virus RNA then decreased, while serum alanine aminotransferase levels fluctuated with multiple peaks. In sporadic cases, titers of hepatitis C virus RNA had already reached a high level (7.0-7.5) at the first alanine aminotransferase peaks 2-3 weeks after the clinical onset. In chronic hepatitis C virus infection, titers of hepatitis C virus RNA remained high for follow-up periods of 6-12 years in patients with chronic active hepatitis. These results indicate that the replication of hepatitis C virus rose to a high level in the early phase of infection and that a high replicative level of hepatitis C virus might be related with progression of liver disease in the chronic phase of infection.

Acute Disease↗
PubMed1994

Hepatitis C virus genotype and RNA titer in the progression of type C chronic liver disease.

Hepatitis C virus genotype and the amounts of circulating HCV RNA are the most important factors in determining the efficacy of interferon therapy for chronic hepatitis C. To clarify the correlation of these two factors to the progression of liver disease, we classified 148 Japanese patients with type C chronic liver disease into genotypes and also measured their HCV RNA titers (logarithmic transformed copy number/ml serum) by competitive reverse transcription-polymerase chain reaction. We found type II in 23 (76.7%) of 30 patients with chronic persistent hepatitis, 34 (79.1%) of 43 with chronic active hepatitis, 29 (72.5%) of 40 with cirrhosis and 30 (85.7%) of 35 with hepatocellular carcinoma. Thus, there was no significant difference in the prevalence of type II among the various stages of chronic liver disease. We also found the RNA titer to be significantly higher in patients with chronic active hepatitis (8.0 +/- 0.8) than in those with chronic persistent hepatitis (7.0 +/- 1.0, p < 0.001), and also those with cirrhosis (7.6 +/- 0.8, p < 0.05) or hepatocellular carcinoma (7.7 +/- 0.8, p < 0.05). When the titers were compared among genotypes, there was no significant difference between type II and III at any stage (type II vs. type III: chronic persistent hepatitis, 7.2 +/- 1.0 vs. 6.7 +/- 0.8; chronic active hepatitis, 8.1 +/- 0.7 vs. 7.8 +/- 1.0; cirrhosis, 7.7 +/- 0.8 vs. 7.8 +/- 0.7; hepatocellular carcinoma, 7.7 +/- 0.8 vs. 7.8 +/- 0.5). In conclusion, although genotype affects interferon therapy efficacy, it seems to have little influence on serum RNA levels and the progression of type C chronic liver disease.

Adult↗
PubMed1994

Hepatitis C virus replication and antibodies to structural and nonstructural viral proteins in chronic hepatitis C.

The correlation between hepatitis C virus replication and antibodies to both structural (core) and nonstructural (C100-3) hepatitis C virus proteins (anti-HCVcore and anti-C100-3, respectively) was assessed. The concentration of serum hepatitis C virus RNA was determined by a competitive reverse transcription-polymerase chain reaction assay, and antibody titers were determined by endpoint dilution. No correlation was found between viremic levels and antibody titers in 42 chronic hepatitis C patients. At the end of a 6-month course of interferon-alpha therapy, 18 patients became negative for hepatitis C virus RNA. In the other 24 patients, post-treatment viremic levels ranged from 10(-6.5)-10(0.5) of pretreatment levels. Both anti-C100-3 and anti-HCVcore frequently decreased in patients whose viremic levels dropped to the negative range or to < 10(-2) of pretreatment levels. Anti-C100-3 decreased in all such cases (25/25), while anti-HCVcore decreased in 18/25 (72%) (p < 0.01), indicating that anti-C100-3 is more likely to decrease following suppression of viral replication than anti-HCVcore. These data suggest that hepatitis C virus antibodies may serve as a marker of suppression of viremia following interferon therapy even in patients who do not clear the virus.

Adult↗
PubMed1994

Hepatitis C virus antibody and hepatitis C virus replication in chronic hepatitis B patients.

We assessed hepatitis C virus infection in 156 chronic hepatitis B patients using second-generation hepatitis C virus antibody (anti-HCV). Active virus replication was further investigated in anti-HCV-positive cases by means of polymerase chain reaction assay for the detection of serum hepatitis C virus RNA. Anti-HCV prevalence was higher in patients negative for hepatitis B e antigen (HBeAg) (10/48, 21%) than in HBeAg-positive patients (10/108, 9%) (p < 0.05), and the reactivity (cut-off index) in anti-HCV enzyme-linked immunosorbent assay of the positive cases was significantly higher in HBeAg-negative patients (4.1 +/- 0.1) than in -positive ones (3.6 +/- 0.6) (p < 0.05). The prevalence of hepatitis C virus RNA in anti-HCV-positive cases was also higher in the HBeAg-negative group (9/10, 90%) than in the -positive group (3/10, 30%) (p < 0.01). Viremia was found in association with high reactivity in anti-HCV ELISA (cut-off index > 3.5) in both groups. Nine (90%) of 10 such cases were viremic in the HBeAg-negative group compared with three (43%) of seven in the HBeAg-positive group (p < 0.05). These results suggest that hepatitis C virus replication may be influenced by hepatitis B virus replicative states, indicating possible interference between hepatitis B and C viruses.

Adult↗
PubMed1994

IgG and IgM core antibodies and viral replication in hepatitis C virus carriers.

We studied IgG and IgM antibodies to hepatitis C virus core protein (anti-HCVcore) in relation to serum virus RNA levels in 71 hepatitis C virus carriers. Viremic levels ranged from 10(4)-10(9) copies/ml and were high in 34 chronic active hepatitis patients compared with 17 asymptomatic carriers and 20 cases of chronic persistent hepatitis (p < 0.01). IgG anti-HCVcore was found in 67/71 (94%), but four asymptomatic carriers with low levels of viremia (10(4)-10(5.5) copies/ml) tested negative. IgM anti-HCVcore was found in patients with high levels of viremia (10(8)-10(9) copies/ml), and one (6%) asymptomatic carrier and nine (26%) chronic active hepatitis patients tested positive. In chronic hepatitis patients, viremic levels were significantly higher in cases positive for IgM anti-HCVcore than in negative ones (p < 0.01). However, no correlation was found between the occurrence of IgM anti-HCVcore and serum aminotransferase levels or the histologic activity index. These findings suggest that although IgG anti-HCVcore is sensitive, low viremic patients can escape this screening, and that the IgM anti-HCVcore is induced in association with high levels of virus replication.

Adult↗
PubMed1994

Gastroenterology.

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Gastroenterology↗
PubMed1994

Metabolic and biosynthetic alterations in cultured astrocytes exposed to hypoxia/reoxygenation.

To investigate the astrocyte response to hypoxia/reoxygenation, as a model relevant to the pathogenesis of ischemic injury, cultured rat astrocytes were exposed to hypoxia. On restoration of astrocytes to normoxia, there was a dramatic increase in protein synthesis within 3 h, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of metabolically labeled astrocyte lysates showed multiple induced bands on fluorograms. Levels of cellular ATP declined during the first 3 h of reoxygenation and the concentration of AMP increased to approximately 3.6 nmol/mg of protein within 1 h of reoxygenation. Reoxygenated astrocytes generated oxygen free radicals early after replacement into ambient air, and addition of diphenyliodonium, an NADPH oxidase inhibitor, diminished the generation of free radicals as well as the induction of several bands on fluorogram. Although addition of cycloheximide on reoxygenation resulted in inhibition of both astrocyte protein synthesis and accumulation of cellular AMP, it caused cell death within 6 h, suggesting the importance of protein synthesis in adaptation of hypoxic astrocytes to reoxygenation. Potential physiologic significance of biosynthetic products of astrocytes in hypoxia/reoxygenation was suggested by the recovery of glutamate uptake. These results indicate that the astrocyte response to hypoxia/reoxygenation includes generation of oxygen free radicals and de novo synthesis of products that influence cell viability and function in ischemia.

Adenosine Monophosphate↗
PubMed1994

Identification and diameter assessment of gastric submucosal vessels using infrared electronic endoscopy.

In this study, an electronic endoscope was applied for observation of gastric submucosal vessels, with infrared illumination, in anesthetized dogs. An in-vivo spectrophotometry showed that infrared light at 620-820 nm penetrates the abdominal and gastric wall. During the endoscopy performed in dogs, the infrared radiation penetrated the abdominal wall and gastric wall from the outside, and was detected by the endoscope's charge-coupled device. A television monitor displayed a network of gastric vasculature, which was identified as veins in the gastric wall by injecting saline or indocyanine green into the vein. Using this system, it was possible to measure venous diameters of more than 0.2 mm by comparison with a reference wire. The diameter obtained by the image analysis correlated lineally to that of a vascular template prepared from the same stomach. Thus, it may become possible to assess gastric submucosal hemodynamics using infrared endoscopy, a new application in electronic endoscopy.

Abdominal Muscles↗
PubMed1994

Adenosine blockade during reperfusion reverses the infarct limiting effect in preconditioned canine hearts.

OBJECTIVES: The aim was to investigate whether adenosine release after reperfusion contributes to infarct limitation by ischaemic preconditioning. METHODS: Dogs underwent preconditioning with four 5 min cycles of left anterior descending coronary artery (LAD) occlusion and reperfusion, followed by 90 min LAD occlusion and 5 h reperfusion with or without the non-specific adenosine receptor blocker, 8-phenyltheophylline (8-PT). Infarct size was assessed by a dual staining method with triphenyltetrazolium chloride and Evans blue. Blood flow measurements in the subendocardial region were made by infusion of coloured microspheres before occlusion and midway through the sustained occlusion. Transcardiac alteration of neutrophillic function was assessed by luminol-enhanced whole blood chemiluminescence induced by zymosan. RESULTS: Infarct size was significantly reduced in the preconditioned dogs [12.5(SEM 4.0)%, n = 10, p < 0.01] compared with the control dogs [40.5(6.1)%, n = 10], an effect significantly reduced by the 8-PT treatment [23.4(4.9)%, n = 8]. Treatment with 8-PT without ischaemic preconditioning had no effect on infarct size [42.8(6.3)%, n = 7]. There was no difference in myocardial blood flow in the ischaemic or non-ischaemic subendocardial tissue between any pair of the four groups. The ratio of whole blood chemiluminescence in the cardiac vein to that in the carotid artery was considerably reduced in preconditioned dogs compared with that in control dogs after reperfusion. Myeloperoxidase activity in the ischaemic myocardium and the peripheral neutrophil count at the end of the experiment were both also decreased compared with control dogs. In preconditioned dogs treated with 8-PT, neutrophillic function in the coronary circulation after reperfusion was increased compared with that in both controls and preconditioned dogs with no 8-PT treatment. There was no difference in neutrophillic function between the 8-PT-treated dogs with or without ischaemic preconditioning. Treatment with 8-PT increased myeloperoxidase activity in the ischaemic myocardium of the preconditioned dogs, and no difference was seen in activity between dogs treated with 8-PT with or without ischaemic preconditioning. CONCLUSIONS: An adenosine receptor blocker caused a moderate but significant reversal of infarct limitation by ischaemic preconditioning associated with a significant increase of neutrophillic function in the coronary circulation during early reperfusion.

Animals↗
PubMed1994

Hepatitis C virus antibodies and virus replication in asymptomatic blood donors.

We assessed hepatitis C virus (HCV) infection in 99 asymptomatic blood donors positive using a first-generation HCV antibody assay. When tested with second-generation assays, 86 (87%) donors were reactive (group 1), 2 (2%) were indeterminate (group 2), and 11 (11%) were non-reactive (group 3). Viraemia was revealed by polymerase chain reaction in all group 1 cases. The 2 group 2 cases and 6 (55%) group 3 cases were also viraemic. Viraemia was confirmed by a branched DNA assay in the 2 group 2 cases and 4 (36%) group 3 cases. Serum HCV RNA levels were further studied using a competitive reverse transcription-polymerase chain reaction assay. All cases in groups 2 and 3 were low viraemic (range 10(4)-10(5.5) copies/ml) compared with the 9 group 1 cases examined (range 10(7)-10(9) copies/ml). No correlation was evident between viraemic levels and antibody cut-off index in the first-generation assay. These findings indicate the possibility that low levels of viraemia can occur in individuals non-reactive in second-generation HCV antibody assays.

Adult↗
PubMed1994

Endothelin-1 is involved in hepatic sinusoidal vasoconstriction after ischemia and reperfusion.

Endothelin-1 (ET-1), a vasoactive peptide, causes a significant rise in portal vein pressure, which is most likely a result of severe vasoconstriction in the liver. In this study, the effect of ET-1 on sinusoidal vasoconstriction in the liver after ischemia and reperfusion was directly investigated using intravital microscopy. In anesthetized female Sprague Dawley rats (200-250 g) ischemia of the median and left liver lobes was induced for 90 min by temporary ligation of the left pedicle. After declamping and a 90-min reperfusion period, the livers were exposed for intravital microscopy. Using a Nikon MM-11 fluorescence microscope (545 nm, 330x), a CCD camera (Cohu FK 6990), and a SVHS video recording unit, the hepatic microcirculation was directly investigated. Besides sham groups, two ischemia groups were studied, receiving ET-1 antiserum (anti-ET-1; 0.5 ml; Peptide Inst., Osaka, Japan) or NaCl 0.9% (0.5 ml) 5 min prior to reperfusion of the liver (n = 6/group). Following a transient drop in the mean arterial blood pressure in the anti-ET-1-treated groups, comparable systemic hemodynamic conditions among the four groups were noted during intravital microscopic assessment at the end of the 90-min reperfusion period. Reduction in the sinusoidal diameters during postischemic reperfusion (7.7 +/- 0.5 microm) was prevented by anti-ET-1 treatment (9.6 +/- 0.25 microm; P < 0.01; mean + SEM) back to control values (9.6 +/- 0.32 microm), while most of other microcirculatory parameters did not show significant differences. The results supported further the role of ET-1 in dysregulation of the sinusoidal vascular tone in the liver, e.g., after ischemia and reperfusion.

Animals↗
PubMed1994

New method for quantitatively determining aortic regurgitant volume using Doppler color flow imaging: experimental validation study.

We have developed a method to provide the two-dimensional distribution of blood flow velocity and the blood flow volume rate in the ascending aorta from the cross-sectional Doppler color flow image. Regional blood flow velocities were determined by converting color intensities of the cross-sectional Doppler color flow image into the corresponding flow velocities with the correction with the spatial ultrasound beam incident angle. The spatial ultrasound beam incident angle was estimated from the geometric characteristics of the color flow image contour. The method was validated in a steady flow model circuit comparing the calculated flow volume rates by the method with those simultaneously measured by an electromagnetic flowmeter. We performed an open chest dog experiment and calculated the blood flow volume rate at the ascending aorta before and after the aortic regurgitation was made. The calculated ejection flow volume rate and regurgitant volume were validated by the comparison with those simultaneously measured by an electromagnetic flowmeter. Based on these data, we can conclude that the current method provides accurate measurements of regurgitant volume as well as ejection flow volume rate in the ascending aorta.

Animals↗
PubMed1994

Effect of addition of hyaluronic acid to highly concentrated insulin on absorption from the conjunctiva in conscious diabetic dogs.

Insulin absorption from the conjunctiva was investigated in five pancreatectomized diabetic mongrel dogs, with the nasolacrimal ducts occluded by micro plugs to prevent insulin absorption from nasolacrimal membrane. In the anaesthetized state, highly concentrated porcine insulin (1000 units mL-1, pH 7.4) was absorbed rapidly and significantly from the conjunctiva. Plasma immunoreactive insulin concentrations increased significantly up to 3 h after insulin administration to conjunctival membranes. Plasma glucose concentration decreased significantly compared with saline control experiments after insulin administration (10 units kg-1) at 3 h (8.3 +/- 0.1 vs 15.6 +/- 0.6 mmol, P < 0.01). However, in the conscious state, there was no significant increase in the plasma insulin levels after topical insulin administration. To improve insulin absorption in the conscious state, we examined the effect of increasing viscosity of insulin preparation with hyaluronic acid. In anaesthetized experiments, there were no significant changes in the bioavailability of insulin after addition of hyaluronate (0.84 +/- 0.11 vs 0.87 +/- 0.05%). In the conscious state, with addition of hyaluronic acid, the area under the curve of plasma insulin concentration was significantly increased (1842 +/- 383 vs 75 +/- 24 m units min L-1, P < 0.01). The bioavailability of insulin absorption was significantly increased after addition of hyaluronate (0.68 +/- 0.14 vs 0.03 +/- 0.01%, P < 0.01). From this study we could demonstrate that the conjunctiva is a potential route for insulin administration, and increased viscosity by the addition of hyaluronate was found effective in increasing the bioavailability of insulin absorption from conjunctival membrane in the conscious state.

Absorption↗
PubMed1994

Response to osmotic stimuli in mesangial cells: role of system A transporter.

It has been suggested that mesangial cells have an osmoregulatory mechanism like that of renal medullary cells, such as intracellular accumulation of polyols in response to hypertonicity. We examined osmoregulatory role of neutral amino acids transported by system A in cultured mesangial cells. The contents of almost all amino acids increased under hypertonic conditions to more than twice the value in isotonic cells. In hypertonic cells, the system A transport activity, measured by Na(+)-dependent 2-(methylamino)isobutyric acid (MeAIB) uptake, was 3.8-fold the uptake in isotonic cells, reaching a maximum 16 h after the switch to hypertonic medium. The response to hypertonicity was the result of an increase in maximal velocity without change in Michaelis constant and was dependent on RNA and protein synthesis. When medium osmolality decreased from hypertonic to isotonic, MeAIB uptake reverted to the isotonic level within 16 h and a large transient efflux of L-proline occurred within 10 min. These results suggest that mesangial cells respond to extracellular hypertonicity by increasing system A transport activity and neutral amino acids can function as compatible osmolytes in mesangial cells.

Amino Acids↗
PubMed1994

Calcium overload and cardiac myocyte cell damage induced by arachidonate lipoxygenation.

The accumulation of arachidonic acid and lipoxygenase metabolites of arachidonate occurs in ischemic-reperfused myocardium. Although lipoxygenase inhibitors have been shown to attenuate myocardial infarct size after ischemia-reperfusion, the relationship between arachidonate lipoxygenation and myocardial injury remains unclear. To investigate the direct effect of arachidonate lipoxygenation on cardiac myocytes, isolated rat cardiac myocytes loaded with indo 1 were superfused with Tyrode solution containing arachidonic acid mixed with soybean lipoxygenase. Although neither arachidonic acid nor lipoxygenase alone had any effects, arachidonic acid plus lipoxygenase induced an increase in the twitch amplitude associated with an increased intracellular Ca2+ concentration ([Ca2+]i) and irreversible hypercontracture. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, blocked these effects. Linolenic acid, which is also a lipoxygenase substrate, caused the same effects as arachidonic acid in the presence of lipoxygenase, whereas oleic and stearic acid, which do not function as lipoxygenase substrates, did not. Both ascorbic acid and alpha-tocopherol attenuated an increase in [Ca2+]i and the cellular damage, whereas nicardipine and superoxide dismutase had no effects. These results suggest that lipoxygenase metabolites of arachidonic acid cause intracellular Ca2+ overload and cellular damage to cardiomyocytes, probably through augmentation of lipid peroxidation of the cell membranes by free radicals.

Animals↗
PubMed1994

AICA riboside improves myocardial ischemia in coronary microembolization in dogs.

This study was undertaken to examine whether 5-amino-4-imidazolecarboxamide (AICA) riboside (acadesine), which augments adenosine release in ischemic myocardium, further attenuates ischemic injury after acute coronary microembolization. The left anterior descending coronary artery was cannulated and perfused with blood from the left carotid artery in 46 dogs, and coronary blood flow (CBF) of the perfused area was measured. In 12 dogs, 15-microns microspheres (5.0 x 10(4)/ml) were injected repeatedly until CBF approached zero. Changes in CBF, fractional shortening, lactate extraction ratio, and adenosine release were measured with and without administration of AICA riboside. In the control group (n = 7), CBF increased to 154 +/- 11 ml.100 g-1.min-1 at 16-30% of total coronary embolization, and adenosine release was 6.1 +/- 1.0 nmol.100 g-1.min-1. Administration of AICA riboside (n = 5) enhanced coronary hyperemia (187 +/- 8 ml.100 g-1.min-1, P < 0.05), adenosine release (11.9 +/- 0.9 nmol.100 g-1.min-1, P < 0.001), and myocardial adenosine content (0.434 +/- 0.069 vs. 0.118 +/- 0.019 nmol/mg wet wt, P < 0.01) and attenuated decreases in fractional shortening and lactate extraction ratio. AICA riboside preserved myocardial tissue ATP content of the embolized area. The administrations of 8-phenyltheophylline (n = 12) and alpha,beta-methyleneadenosine 5'-diphosphate (n = 10) abolished the beneficial effects of AICA riboside. Furthermore, AICA riboside increased ectosolic and cytosolic 5'-nucleotidase activity of the embolized myocardium (n = 12). Thus we conclude that AICA riboside attenuates contractile and metabolic dysfunction by enhancing adenosine release via activation of ectosolic 5'-nucleotidase and inducing local hyperemia in acute coronary microembolization.

5'-Nucleotidase↗
PubMed1994

Ebselen protects against ischemia-reperfusion injury in a canine model of myocardial infarction.

We investigated the infarct-limiting effect of a selenoorganic compound, ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], in a canine coronary artery occlusion-reperfusion model of myocardial infarction. Ebselen, administered 1 h before coronary artery occlusion (50 mg/kg po), significantly reduced infarct size resulting from 90-min coronary artery occlusion followed by 5-h reperfusion (P < 0.05). When we examined the relation between infarct size and plasma ebselen level, infarct size in dogs with plasma ebselen level > 5 microM before reperfusion was significantly smaller (P < 0.05) than that in dogs with plasma ebselen level < or = 5 microM or in the control dogs. This infarct limitation produced by ebselen treatment was associated with an increase in reduced glutathione content and a reduction in myeloperoxidase activity in the ischemic myocardium. No differences between the control and treated groups were found in hemodynamic parameters or regional myocardial blood flow in the course of the experiment. The findings of this study demonstrate that ebselen effectively reduced the myocardial ischemia-reperfusion injury associated with preservation of the glutathione redox state and a reduction in neutrophil infiltration into the ischemic myocardium.

Animals↗