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T Kamada

Publications and source records attributed to T Kamada.

At least 361 records · Page 20Linked to original sources
PubMed1993

Alpha-interferon enhances gamma-interferon production of peripheral blood mononuclear cells pre-activated with phytohemagglutinin.

The question of whether the state of T cell activation is responsible for gamma-interferon production in response to alpha-interferon was determined. When peripheral blood mononuclear cells were pre-incubated with phytohemagglutinin for 3 days, their gamma-interferon production was found to be augmented by alpha-interferon, accompanied by an increased proportion of DR-positive T cells. This did not occur with fresh cells. The effect was dose-dependent and inhibited by anti-alpha-interferon antibody. Therefore, alpha-interferon was considered to enhance the production of gamma-interferon of pre-activated peripheral blood mononuclear cells but not of resting ones. In conclusion, alpha-interferon augmented the production of gamma-interferon of peripheral blood mononuclear cells only when they had already been activated, suggesting a role of alpha-interferon as a modulator of the cellular immune response.

Flow Cytometry↗
PubMed1993

Quantitative analysis of hepatitis C virus RNA: relationship between the replicative level and the various stages of the carrier states or the response to interferon therapy.

The authors quantified hepatitis C virus (HCV) RNA in serum by the competitive RT-PCR assay to correlate the replicative level of HCV with [1] various stages of the carrier states or [2] a sustained response to interferon therapy. The competitive RT-PCR assay employed is based on co-amplification of the target RNA with known amounts of synthetic mutated RNA having a novel restriction endonuclease (EcoRI) site. The titer of circulating HCV RNA defined as log10 (copy numbers/ml serum) were lower in asymptomatic blood donors (5.4 +/- 2.0) and in patients with chronic persistent hepatitis (7.3 +/- 1.1) compared with those having chronic active hepatitis (7.9 +/- 0.8), liver cirrhosis (7.8 +/- 0.7) and hepatocellular carcinoma (7.9 +/- 0.7). The initial titer of circulating HCV RNA of long-term responders before interferon therapy (7.1 +/- 1.2) was significantly lower than that of short-term responders (8.3 +/- 0.5) and non-responders (8.1 +/- 0.4). Multivariate multiple logistic regression showed that the titer of HCV RNA before therapy was the strongest independent predictor of a sustained response to interferon therapy. These results showed that the replicative level of hepatitis C virus is higher in advanced liver disease and that the replicative state of HCV is the most important factor influencing sustained response to interferon treatment.

Adult↗
PubMed1993

Antibodies to hepatitis C virus and hepatitis C virus infection.

The authors studied the interrelationship of antibody to hepatitis C virus core protein (anti-HCV core), antibody to C100-3 antigen (anti-C100-3) and serum hepatitis C virus RNA positivity in chronic liver disease patients. Anti-HCVcore was detected with high titers in 95% (69/73) of chronic non-A, non-B hepatitis patients, while anti-C100-3 was found in 60% (44/73). A close relationship was observed between detection of anti-HCVcore and viremia. Anti-HCVcore was also detected with low titers in 24% (10/41) of hepatitis B virus carriers negative for anti-C100-3. Hepatitis C virus RNA was found in 3 of the 10 anti-HCVcore-positive carriers. A significant correlation was observed between the occurrence of high titers of anti-HCVcore and serum hepatitis C virus RNA positivity. In chronic hepatitis C patients treated with interferon-alpha, a sustained reduction of anti-HCVcore was more closely associated with sustained virus clearance than that of anti-C100-3. These results indicate that anti-HCVcore may serve as a reliable marker of hepatitis C virus infection.

Antigens, Viral↗
PubMed1993

Cell kinetics of mucosal atrophy in rat stomach induced by long-term administration of ammonia.

BACKGROUND: Helicobacter pylori produces ammonia in the stomach from urea. The present study was undertaken to clarify whether ammonia has an etiological role in H. pylori-associated gastric mucosal atrophy. METHODS: Ammonia at 0.01% was administered as drinking water for 8 weeks and mucosal cell migration rate and cell proliferation were investigated in rat stomach. RESULTS: Long-term administration of 0.01% ammonia for 4-8 weeks decreased mucosal thickness in the antrum but not in the body. Acceleration of cell migration preceded the occurrence of mucosal atrophy. Labeling indices in both antral and body mucosa significantly increased in all ammonia-treated groups, compared with those of the control group. In the antrum, the proliferative zone was significantly enlarged as mucosal atrophy developed, whereas, in body mucosa, enlargement of the proliferative zone occurred despite the absence of mucosal atrophy. CONCLUSION: Ammonia at 0.01% accelerates epithelial migration, especially in the antrum, leading to mucosal atrophy. Acceleration of epithelial proliferation occurs during the development of mucosal atrophy.

Ammonia↗
PubMed1993

Quantitative analysis of hepatitis C virus RNA in serum during interferon alfa therapy.

BACKGROUND: Interferon alfa is effective for controlling disease activity in chronic hepatitis C. However, many responders suffer relapse after cessation of therapy. In the present study, the serum concentration of hepatitis C virus RNA was correlated with a sustained response to interferon therapy. METHODS: Fifty-three patients with chronic hepatitis C received a 26-week course of interferon alfa. Hepatitis C virus RNA was quantitated in serum at the beginning and end of treatment using a competitive assay that combined reverse transcription and polymerase chain reaction. RESULTS: In long-term responders, whose alanine aminotransferase levels remained within the normal range during the 24 weeks after therapy, the titer of viral RNA (logarithmic transformed copy numbers per milliliter of serum) before therapy (7.1 +/- 1.2) was significantly lower (P < 0.001) than that of short-term responders (8.3 +/- 0.5) who had a relapse within the 24 weeks after therapy and nonresponders (8.1 +/- 0.4). Multivariate multiple logistic regression showed that the titer of viral RNA before therapy was the strongest independent predictor of a sustained response to interferon-alfa therapy (P = 0.002). CONCLUSIONS: The titer of hepatitis C virus RNA is the most important factor influencing the sustained response to interferon treatment.

2',5'-Oligoadenylate Synthetase↗
PubMed1993

Improvement in blunted glucagon response to insulin-induced hypoglycemia by strict glycemic control in diabetics.

To elucidate the mechanism of impaired pancreatic A cell function in hypoglycemia in diabetics, the effect of long-term strict glycemic regulations on hypoglycemia-induced glucagon secretion was studied. Firstly, the effect of plasma insulin concentrations on suppressing A cell was studied in healthy volunteers by injecting insulin at doses of 0.1 U/kg and 0.3 U/kg. With 0.3 U/kg of insulin, the rate of fall in glycemia and the nadir of blood glucose were made similar to those with 0.1 U/kg of insulin by glucose infusion with artificial endocrine pancreas. Plasma glucagon response after 0.3 U/kg of insulin was significantly suppressed as compared to that after 0.1 U/kg of insulin, demonstrating that not only hypoglycemic stimulus but also plasma insulin concentration were important determinants responsible for glucagon secretion in insulin-induced hypoglycemia. Secondly, effect of strict glycemic control was studied. Short-acting insulin at a dose of 0.1 U/kg was injected in an intravenous bolus form into 12 insulin-dependent (IDDM) and 9 non-insulin-dependent (NIDDM) diabetics before and 1-3 months after strict glycemic control with multiple insulin injections therapy. Before strict glycemic regulations in IDDM, no significant rise in plasma glucagon concentrations was observed during the insulin-induced hypoglycemia. In NIDDM, a rise in plasma glucagon concentrations was observed, though the response was delayed. After strict glycemic regulations, in patients with residual endogenous insulin secretion, the glucagon response to hypoglycemia improved considerably in IDDM and normalized in NIDDM. In IDDM and NIDDM, improvement in glucagon response to hypoglycemia related positively to daily urinary secretion rate of C-peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Clinical usefulness of a non-wiping type glucose meter in diabetic patients.

A non-wiping type glucose meter using electrochemistry was developed. The glucose sensor strip has a sophisticated micro-structure for aspirating blood automatically. The meter compensates for drift of sensor output due to temperature change of the atmosphere. Mounting blood on the sensing site and wiping blood and precise time are no longer required. Range of measurement is 40-500 mg/dl. Reading of the meter for standard solutions of 90 or 360 mg/dl glucose showed negligible drift of measurement from 10.5 degrees C to 38.5 degrees C. The correlation between plasma glucose concentrations as determined by the meter and that by a Glucose Analyzer 2 was 0.995 with a slope of 1.00 and intercept of -0.65 (n = 48). In the case of blood glucose concentration (Y), the values were Y = 1.06X-0.91, r = 0.987, n = 62. This meter is quite easy to use and is highly accurate for glucose monitoring in patients regardless of operation skill. It should thus be readily applicable to diabetic patients.

Blood Glucose↗
PubMed1993

Detection of hepatitis C virus RNA in liver tissues by an in situ hybridization technique.

Hepatitis C virus (HCV) infection of cells in liver tissues was determined by detecting HCV RNA by an in situ hybridization technique using synthetic oligonucleotide probes derived from the 5'-non-coding and core regions of HCV genome. Aggregated silver grains indicating hybridization with HCV RNA were observed over the nuclei as well as the cytoplasm of hepatocytes with none on non-parenchymal cells. The specificity of the hybridization was confirmed by absence of autoradiographic signals after ribonuclease predigestion, addition of an excess of non-labeled probes, or application of an M 13 probe. The hepatocytes with HCV RNA-positive signals were scattered in the periportal and mediolobular zones of liver lobules rather than in the pericentral zones. Fifteen out of 33 biopsy specimens from patients with chronic HCV infection studied had the HCV RNA-positive hepatocytes. These cells were more frequently detected in specimens with advanced periportal, bridging and intralobular necrosis but showed no correlation with the extent of inflammatory cell infiltration. These findings suggest a close correlation between the detection of HCV RNA in hepatocytes and advanced necrosis of the specimens.

Adult↗
PubMed1993

Serodiagnosis of chronic hepatitis C in Japan by second-generation recombinant immunoblot assay.

The seroprevalence of antibodies to hepatitis C virus (HCV) by a second-generation recombinant immunoblot assay (RIBA-2) was tested using 4 recombinant antigens. The results were correlated with those of C100-3 enzyme-linked immunosorbent assay (ELISA) and with the detection of HCV-RNA sequences by the polymerase chain reaction. Sera were obtained from 27 C100-3 ELISA-positive Japanese patients with chronic non-A, non-B liver disease and from 29 C100-3 ELISA-negative patients. All C100-3 ELISA-positive patients and 19 (66%) out of 29 C100-3 ELISA-negative patients reacted to two or more RIBA-2 antigens (reactive by RIBA-2). Of the remaining 10 C100-3 ELISA-negative patients, one patient reacted to just one antigen (indeterminate by RIBA-2), while 9 reacted to none of the 4 antigens (non-reactive by RIBA-2). Forty-three (93%) of the 46 RIBA-2-reactive patients and the single RIBA-2-indeterminate patient tested positive for HCV-RNA sequences, whereas only one (11%) of the 9 RIBA-2-non-reactive patients tested positive. These findings indicate that HCV infection is more prevalent than expected from the results of C100-3 ELISA, and that RIBA-2 is a more sensitive assay for estimating the presence of HCV infection in chronic liver disease.

Aged↗
PubMed1993

Expression of DNA methyltransferase in LEC rats during hepatocarcinogenesis.

The Long-Evans with a cinnamon-like color (LEC) rat is a mutant of the Long-Evans strain that develops hereditary hepatitis and hepatoma with ageing. Age-related changes in the mRNA expression of DNA methyltransferase (DNA MTase) were examined in livers of LEC rats using Long Evans with an agouti color (LEA) rats as controls. A dramatic increase in the expression of this mRNA was observed in LEC rats at 20 weeks when acute hepatitis appeared. Their high mRNA levels were maintained until 52 weeks of age. The mRNA expression as well as DNA MTase activities were found to be higher in cancer lesions than in adjacent normal tissue. These increases may be related to liver regeneration and to early events in cellular transformation of LEC rats.

Aging↗
PubMed1993

Role of adenosine and its interaction with alpha adrenoceptor activity in ischaemic and reperfusion injury of the myocardium.

Adenosine is recognised as an important regulator of myocardial function and coronary vascular tone in the ischaemic myocardium. It is produced by the enzymatic dephosphorylation of 5'-AMP by 5'-nucleotidase and the hydrolysis of SAH by SAH-hydrolase. 5'-Nucleotidase is thought to contribute to adenosine production aside from the accumulation of 5'-AMP in the ischaemic myocardium, while the hydrolysis of SAH plays a major role in adenosine production in the normoxic myocardium. 5'-Nucleotidase activity is reported to increase adenosine production through accumulation of ATP, ADP, H+, Mg2+ and inorganic phosphate during ischaemia. In addition, we have found that alpha 1 adrenergic receptors, activated in ischaemic hearts, increase both 5'-nucleotidase activity and adenosine production. Inactivation of adenosine deaminase and adenosine kinase may also contribute to adenosine production. On the other hand, the major role of endogenous adenosine is to increase coronary blood flow. This adenosine induced coronary vasodilatation is amplified by alpha 2 adrenoceptor stimulation. Adenosine induced vasodilatation is also enhanced by increasing H+ and opening ATP sensitive K+ channels, which occurs in the ischaemic myocardium. However, coronary vasodilatation is not the only effect of adenosine in the ischaemic myocardium. Stimulation of adenosine A2 receptors coupled to Gs proteins attenuates both free radical generation by activated leucocytes and aggregation of platelets. Adenosine A1 receptor activation coupled to G(i) proteins attenuates beta adrenoceptor mediated increases in myocardial contractility, Ca2+ influx into myocytes, and noradrenaline release from the presynaptic nerves. Any or all of these effects may attenuate ischaemic and reperfusion injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1993

Transcardiac alteration of neutrophil function relates to myocardial ischaemia/reperfusion injury.

OBJECTIVE: The aim was to define the relation between transcardiac changes in neutrophil function in myocardial ischaemia and the progression of myocardial necrosis. METHODS: Samples of blood from carotid artery, jugular vein, and cardiac vein streaming from the ischaemic area were taken simultaneously in a canine coronary occlusion-reperfusion model of myocardial infarction. Neutrophil function was evaluated by neutrophil count, whole blood chemiluminescence and leucocyte infiltration into the ischaemic myocardium. Myocardial necrosis was assessed by plasma creatine kinase and dual staining technique using Evans blue dye and triphenyltetrazolium chloride. Effects of a free radical scavenger, N-2-mercaptopropionyl glycine (MPG), initiated 15 min before reperfusion and continued during the reperfusion phase, were also examined. RESULTS: Whole blood chemiluminescence of the cardiac vein was reduced at 90 min after coronary artery occlusion as compared to carotid artery [5.8(SEM 0.5) v 7.5(0.7) count x 10(3) cell neutrophil-1 x 10 min-1, p < 0.05], and then increased abruptly after reperfusion to peak after 10 min of reperfusion [7.1(0.7) count x 10(3) cell neutrophil-1 x 10 min-1]. The neutrophil count in cardiac venous blood was significantly reduced within 5 min of reperfusion. MPG significantly attenuated the reperfusion associated increase in cardiac vein whole blood chemiluminescence and the decrease in the cardiac venous blood neutrophil count. The increase in myocardial free radical generation 1-3 h after reperfusion, as assessed by the electron paramagnetic resonance spin trapping technique, was reduced markedly, as was the extent of leucocyte infiltration into the ischaemic myocardium. Under these conditions, administration of MPG significantly reduced myocardial infarct size [40.3(4.5)% v 21.4(4.2)%, p < 0.05]. A marked increase in transcardiac creatine kinase release after reperfusion observed in control dogs was also reduced significantly. CONCLUSIONS: A transient alteration of neutrophil function occurs in the coronary circulation immediately after reperfusion, which may augment neutrophil infiltration and free radical generation in the ischaemic myocardium, leading to the propagation of myocardial ischaemia/reperfusion injury.

Animals↗
PubMed1993

Free radical generation coupled with arachidonate lipoxygenase reaction relates to reoxygenation induced myocardial cell injury.

OBJECTIVE: The role of arachidonate lipoxygenase activity in reoxygenation induced cell injury in adult canine cardiac myocytes was investigated. METHODS: The production of hydroxyeicosatetraenoic acids (HETEs), which are lipoxygenase metabolites, was measured with high pressure liquid chromatography in canine cardiac myocytes cultured under hypoxic conditions and then reoxygenated. Free radical generation was evaluated by electron paramagnetic resonance spectroscopy with a spin trapper, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and luminol enhanced chemiluminescence emission. Cell injury was estimated in terms of morphological changes and release of intracellular enzymes. Morphological damage to myocytes was quantified in terms of the percentage of hypercontracted "round" cells. The effects of nordihydroguaiaretic acid, AA-861, mepacrine, indomethacin, aspirin, alpha tocopherol, and 2-0-octadecylascorbic acid (CV-3611) on lipoxygenase metabolism, free radical generation and cell injury were also assessed. RESULTS: Cardiac myocytes produced 5-HETE and 12-HETE at less than 0.1 ng.mg-1 protein under normoxic conditions. Production of HETE was greatly increased at five hours of reoxygenation after 45 minutes of hypoxia [5-HETE = 12.0(SEM 0.5), 12-HETE = 23.6(1.1) ng.mg-1 protein]. Both DMPO-OH adduct generation and chemiluminescence emission were considerably increased after one to three hours of reoxygenation, although they increased only slightly after 45 minutes of hypoxia. After five hours of reoxygenation, long rod cells gradually became deformed; 92.0% of the cells were converted to hypercontracted "round" cells. Cell injury and HETE production were significantly suppressed by nordihydroguaiaretic acid (10 microM), AA-861 (2 microM), and mepacrine (10 microM). Indomethacin (10 microM) and aspirin (50 microM) enhanced cell injury and HETE production. alpha Tocopherol and CV-3611 greatly suppressed cell injury and free radical generation, but not HETE production. CONCLUSION: The arachidonate lipoxygenase metabolic pathway may have an important role in reoxygenation induced myocardial cell injury in adult cardiac myocytes, possibly because of the generation of free radicals.

Animals↗
PubMed1993

Effects of heart rate on left ventricular filling dynamics: assessment from simultaneous recordings of pulsed Doppler transmitral flow velocity pattern and haemodynamic variables.

OBJECTIVE: The effects of heart rate on transmitral flow velocity pattern are still controversial. The aim of this study was to examine the relations between the changes in Doppler echocardiographic variables and those in haemodynamic variables in association with altering heart rate. METHODS: Pulsed Doppler transmitral flow velocity pattern and left atrial and left ventricular pressures were simultaneously recorded at various heart rates (from 80 to 120 beats.min-1) in 14 dogs. RESULTS: As heart rate increased, peak late diastolic filling velocity increased, the time-velocity integral of the early diastolic filling wave decreased, and the deceleration time of early diastolic flow shortened without significant changes in mean values of peak early diastolic filling velocity and acceleration time of early diastolic flow. Peak early diastolic filling velocity increased with heart rate, however, in five dogs and decreased in the other nine dogs. The shortening of the time constant of left ventricular isovolumic relaxation was greater in the five dogs in which peak early diastolic filling velocity increased with heart rate than in the other nine dogs. Results of multiple stepwise linear regression analysis showed that the changes in peak early diastolic filling velocity correlated with the changes in the crossover pressure and peak+dP/dt in addition to the time constant, and that diastolic filling period was not selected as an affecting factor. Changes in the other Doppler echocardiographic variables did not correlate solely with changes in heart rate, or diastolic filling period, but correlated in a complex fashion with the combined changes in haemodynamic variables associated with altering heart rate. CONCLUSIONS: Although transmitral flow velocity pattern changes with altering heart rate, this change is not considered to be a direct effect of alteration in heart rate, but an indirect one through the associated haemodynamic changes including left atrial pressure and left ventricular relaxation and contractility.

Animals↗
PubMed1993

Protective effect of the protease inhibitor leupeptin against myocardial stunning.

To elucidate whether activation of intracellular protease causes the contractile dysfunction of post-ischemic reperfused heart (stunned myocardium), the effect of leupeptin, a cysteine-protease inhibitor, was evaluated in isolated guinea pig hearts. Left ventricular (LV) isovolumic pressure was measured in hearts reperfused after global ischemia (15 min, 37 degrees C). Recovery of developed pressure during reperfusion in hearts treated with 50 microM leupeptin was significantly greater than that in untreated hearts [94.3 +/- 3.2% of control, n = 11 (mean +/- SEM] vs. 78.1 +/- 3.1%, n = 14), and was almost identical to that in nonischemic control (93.5 +/- 1.6%, n = 11). Maximal Ca(2+)-activated pressure, the intact-heart correlate of maximal Ca(2+)-activated force, was also evaluated at the end of experiments during tetani elicited by rapid pacing after exposure to ryanodine. Maximal Ca(2+)-activated pressure in hearts treated with leupeptin (168 +/- 4.6 mm Hg) was significantly higher than in untreated stunned hearts (144.5 +/- 5.7 mm Hg), but significantly lower than in nonischemic control (198.4 +/- 5.5 mm Hg). These results indicate that leupeptin has a protective effect against myocardial stunning. In coupling with previous reports of transient increase in intracellular [Ca2+] during ischemia and/or reperfusion, activation of proteases by Ca2+ overload is suggested to play a significant role in myocardial stunning.

Animals↗
PubMed1993

Is postoperative radiotherapy beneficial in the management of stage I-II squamous-cell carcinoma of the uterine cervix with negative metastatic nodes and positive parametrial involvement?: A retrospective review of 70 patients.

Seventy patients having squamous-cell carcinoma of the uterine cervix FIGO Stage I-II with negative lymph nodes and positive parametrial involvement received postoperative radiotherapy following radical hysterectomy and pelvic lymphadenectomy. In 48 patients with microscopic parametrial invasion, the 5-year survival rate was 92%. The other 22 patients with macroscopic parametrial involvement had a 5-year survival rate of 75%. The overall recurrence rate was 13% (9 of 70). The sites of failure were 3 pelvic alone, 5 distant metastases alone, and 1 combined pelvis and para-aortic lymph node. All of those with recurrence were Stage-II cases. The absolute pelvic-control rate was 94.3% (66/70). Fifty-six percent of the patients experienced mild-to-moderate lymphedema. Severe complications requiring surgical intervention were observed in 6 patients (5 bowel obstructions and 1 femoral head fracture). A review of the literature suggests that early carcinoma can be successfully treated by surgery alone. Taking into consideration the risk and benefits involved, postoperative radiotherapy is not recommended for most cases with cervical carcinoma with negative lymph nodes and positive parametrial involvement in the present form, despite excellent local control. However, no definite conclusion can be drawn from this retrospective analysis.

Adult↗
PubMed1993

Measurement of redox states of mitochondrial cytochrome aa3 in regions of liver lobule by reflectance microspectroscopy.

To evaluate the sublobular distribution of oxygen tension, the redox states of mitochondrial cytochrome aa3 were assessed in local regions of the liver lobule by reflectance microspectroscopy. The reflected light from two focused microspots (20 microns in diam) on the surface of the perfused liver, placed on the stage of microscope, was conducted to the spectrophotometer with two separate light guides, giving the reflectance spectra. The redox state of cytochrome aa3 was calculated from the difference in reflectance between 603 and 630 nm. The degree of cytochrome reduction increased with the stepwise decline of the influent or effluent oxygen concentrations. The local oxygen concentration in periportal region for the half-maximal reduction of cytochrome aa3 was higher than that in pericentral region. In addition, the degree of cytochrome aa3 reduction increased with the distance from the periportal region, reflecting a physiological gradient of oxygen tension along the sinusoidal flow, although with an intersinusoidal heterogeneity within liver lobule.

Animals↗