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Biomedical subjects

T Kumada

Publications and source records attributed to T Kumada.

At least 91 records · Page 5Linked to original sources
PubMed1994

[Clinical study of retreatment of chronic hepatitis C with interferon (IFN) for non-complete responders on initial treatment].

From August 1990 to May 1993, we treated 23 non-complete responders on initial treatment with interferon and studied the factor which affects the effectiveness in the attempt to verify the factors for the selection of patients who are to receive it. Complete response was achieved in 8 (34.8%) patients, while the other 15 patients did not achieve this degree of response. Three patients were of genotype II and 5 of genotype III in these 8 complete responders. All complete responders were patients with relapse who had had normalized serum ALT levels during the initial administration and undetectable HCV-RNA at the end of the period. No patient who failed to achieve normalization of the serum ALT level on initial treatment achieved a complete response on retreatment. HCV-RNA concentration before retreatment was significantly less than the one before initial treatment in 8 complete responders. Interferon retreatment of patients who do not achieve a complete response may be effective in relapsed cases with undetectable HCV-RNA at the end of initial treatment. Selection of patients to receive interferon retreatment requires careful review and consideration of genotype, HCV-RNA concentration, and the clinical response at initial treatment.

Adult↗
PubMed1994

Retreatment of chronic hepatitis C with interferon.

OBJECTIVE: We analyzed the retreatment of chronic hepatitis C with interferon to get the standpoint for the selection of patients to receive it. METHODS: A complete response was defined as continuous normalization of the serum alanine aminotransferase (ALT) level and continuous disappearance of serum hepatitis C virus RNA (HCV-RNA) during interferon administration and more than 6 months after. Patients without complete response were classified as noncomplete responders. From August 1990 to May 1993, we retreated 23 noncomplete responders on initial treatment with interferon and studied the factors that alter the effectiveness. RESULTS: Complete response was achieved in eight (34.8%) patients; the other 15 patients did not achieve this degree of response. Three patients were of genotype II and five were of genotype III in these eight complete responders. All complete responders were patients with relapse who had had normalized serum ALT levels during the initial administration and undetectable HCV-RNA at the end of the period. No patient who failed to achieve normalization of the serum ALT level on initial treatment achieved a complete response on retreatment. HCV-RNA concentrations before retreatment were significantly less than before initial treatment in the eight complete responders. CONCLUSION: Interferon retreatment of patients who do not achieve a complete response may be effective in relapsed cases with undetectable HCV-RNA at the end of initial treatment. Selection of patients to receive interferon retreatment requires careful review and consideration of genotype, HCV-RNA concentration, and the clinical response on initial treatment.

Alanine Transaminase↗
PubMed1994

[Trial of self-management of outpatients with implanted reservoir for arterial infusion of anticancer drugs].

We attempted to instruct the outpatients with malignant liver tumor (metastatic liver cancer and advanced hepatocellular carcinoma) who received intermittent arterial infusion chemotherapy using implanted reservoir to detach the devices for arterial infusion by themselves at home. All patients who received our instruction could master self-detachment at home, which shortened the hospitalized day. And patients' desire for this treatment promoted with improvement of the recognition of their families to participate in treatment together. We experienced no trouble which disturb the treatment. This methods was considered to promote the improvement of QOL of these patients.

Ambulatory Care↗
PubMed1994

[Analysis of methods of administration on local arterial infusion chemotherapy for severe advanced hepatocellular carcinoma].

Between 1986 and 1994, hepatic local arterial infusion chemotherapy with implanted reservoir was performed for 51 patients with hepatocellular carcinoma (HCC) who were not indicated for surgery, PEIT and/or TAE because of the advanced stage of tumors and impaired liver function. We compared direct effects, survival rates, and rates of outpatients by dividing these 51 patients into 3 groups according to the methods of administration--repeated one-shot arterial infusion group, continuous arterial infusion group and intermittent high-dose arterial infusion group. There were no significant differences among these three groups in terms of background factors. The continuous infusion group had significantly better survival rates than the repeated one-shot infusion group, and the survival rate of the intermittent high-dose infusion group was similar to that of the continuous infusion group, although there were no significant differences in effectiveness among the three groups. Patients in the continuous infusion group and intermittent high-dose infusion group could receive almost all of their treatment as outpatients. Furthermore, more patients in the intermittent high-dose infusion group could receive whole treatment without hospitalization than patients in the continuous infusion group. Because intermittent high-dose arterial infusion of 5-FU showed about the same survival rate as continuous arterial infusion and because it can maintain high quality of life, it is suggested to be a standard method for local arterial infusion of 5-FU for severe advanced HCC.

Aged↗
PubMed1994

An antiallergic drug, pemirolast potassium, inhibits inositol 1,4,5-trisphosphate production and Ca2+ mobilization in antigen-stimulated rat basophilic leukemia (RBL-2H3) cells.

An antiallergic drug, pemirolast potassium (TBX) at concentrations between 0.01 and 10 micrograms/ml inhibited antigen (Ag)-stimulated degranulation in RBL-2H3 cells, which have the properties of mucosal mast cells. At the same concentrations, the drug suppressed both the formation of inositol 1,4,5-trisphosphate and the mobilization of Ca2+, indicating the prevention of phospholipase C activation. The production of 1,2-diacylglycerol and phosphatidic acid, which was mainly due to phosphatidylcholine hydrolysis, was also suppressed. Moreover, TBX reduced Ag-induced liberation of arachidonic acid, a precursor of eicosanoids, implying the inhibition of phospholipase A2. These data suggest that TBX inhibits the activation of phospholipase C, leading to decreased formation of the signal transducing molecules necessary for cell activation.

Animals↗
PubMed1993

Potentiation by cholera toxin of bradykinin-induced inositol phosphate production in the osteoblast-like cell line MC3T3-E1.

Cells of the osteoblastic cell line MC3T3-E1 were shown to contain at least three phosphatidylinositol-specific phospholipase C (PI-PLC) isoenzymes (PLC-beta, PLC-gamma and PLC-delta) by Western blotting analysis with various anti-PLC antibodies. Stimulation of inositol phosphate production in MC3T3-E1 cells by bradykinin (BK) occurred via a GTP-binding protein. Inositol phosphate formation on stimulation by BK was not affected by pretreatment with pertussis toxin, whereas it was potentiated by cholera toxin pretreatment. Elevation of cellular cyclic AMP levels by brief pretreatment with dibutyryl cyclic AMP or forskolin failed to enhance the BK-mediated generation of inositol phosphates, but long-term preincubation with these agents partially mimicked the action of the cholera toxin. Cholera toxin also caused an increase in BK receptor number. Cycloheximide, a protein biosynthesis inhibitor, prevented the potentiating actions of the cholera toxin and the cyclic AMP-elevating agents on BK-induced inositol phosphate production, and also inhibited the increase in BK receptor number. The specific binding of [3H]BK to the whole MC3T3-E1 cells in the presence or absence of cholera toxin was completely inhibited by the B2 BK receptor antagonist D-Arg[Hyp3,Thi5,8,D-Phe7]BK, but not by the B1 BK receptor agonist des-Arg9-BK. These data suggest that the activation of PI-PLC induced by cholera toxin in BK-stimulated MC3T3-E1 cells was caused by an enhancement of the synthesis of BK receptor protein(s), at least part of which was mediated by a sustained increase in the intracellular level of cyclic AMP.

Adenosine Diphosphate Ribose↗
PubMed1993

Involvement of tyrosine phosphorylation in IgE receptor-mediated phospholipase D activation in rat basophilic leukemia (RBL-2H3) cells.

The effect of protein tyrosine phosphorylation on phospholipase D (PLD) activation measured by the formation of radiolabeled phosphatidylbutanol (PBut) was examined in rat basophilic leukemia (RBL-2H3) cells stimulated with antigen. The PLD activation elicited by antigen was attenuated dose-dependently by pretreatment with protein tyrosine kinase inhibitors, genistein and ST638. In parallel, tyrosine phosphorylation of 72 kDa protein was inhibited by the same pretreatment. These results, taken together with little effect of genistein on phosphoinositide hydrolysis, suggest that tyrosine kinase may be implicated in the IgE-mediated PLD activation which is regulated by a protein kinase C-independent process.

Animals↗
PubMed1993

Effects of interferon-alpha on serum hepatitis C virus in patients with chronic hepatitis C.

Interferon is beneficial in some patients with chronic hepatitis C. To assess the efficacy of interferon, we used the polymerase chain reaction (PCR) to measure HCV RNA in serial serum samples from 13 chronic hepatitis C patients who were treated with interferon-alpha. Serum alanine aminotransferase (ALT) values normalized in association with the disappearance of serum HCV RNA in nine cases during the therapy. Serum HCV remained negative after the therapy in the three patients who had no relapse, while serum HCV RNA reappeared in the six patients with elevation of ALT values. The persistence of normal ALT levels appears to be correlated with the clearance of the serum HCV. There were two patients whose ALT became normal immediately after the cessation of interferon. Serum HCV was detectable at the end of treatment when serum ALT was elevated, and thereafter serum HCV disappeared. This result suggests an immunomodulatory effect of interferon in the clearance of HCV in some cases. Furthermore, the semiquantitative PCR assay showed that all five patients in whom ALT values were normal at the end of follow-up without detectable serum HCV genome had lower HCV titers in the pretreatment sera than the other eight patients. The detection of HCV RNA by the PCR assay is useful in determining the efficacy of interferon and its mechanisms.

Adult↗
PubMed1993

Post-exercise oxygen uptake kinetics in patients with left ventricular dysfunction.

We assessed the kinetics of oxygen uptake (VO2) after symptom-limited maximal exercise by use of cardiopulmonary exercise testing with a bicycle ergometer in normal subjects and patients with left ventricular dysfunction due to dilated cardiomyopathy. During the first few minutes after the cessation of exercise, the VO2-time relationship showed an exponential-like decrease. A monoexponential curve was fitted to this relationship of the first 3 min after exercise to obtain the time constant of the decrease in VO2 (T(VO2)). The results of exercise testing in 37 normal subjects (25 male and 12 female) revealed that T(VO2) was relatively independent of age and gender. Then, 30 male patients with dilated cardiomyopathy (10 in New York Heart Association functional class I, 12 in class II, and 8 in class III) were evaluated and the results were compared with those of 16 age-matched male control normal subjects. Although the amount of the estimated oxygen debt was smaller in the patient group, the time constant T(VO2) was 117 +/- 8 s for the controls as compared with 130 +/- 14 s for the patients in class I, 153 +/- 13 s for those in class II, and 219 +/- 49 s for those in class III. There were significant correlations between T(VO2) and anaerobic threshold (r = -0.68, p < 0.001), peak VO2 (r = -0.74, p < 0.001), and the increase in VO2 per work rate (r = -0.88, p < 0.001). T(VO2) also correlated with the ventilatory equivalent for carbon dioxide output (VE/VCO2) at peak exercise (r = 0.70, p < 0.001) and the time course of minute ventilation during the early phase of the post-exercise period (r = 0.67, p < 0.001). Thus, the time course of VO2 decrease after symptom-limited exercise is considered to be closely related to exercise capacity and also to the degree of exercise-induced hyperpnea in patients with left ventricular dysfunction.

Adult↗
PubMed1993

[Pathophysiology and current therapy of congestive heart failure due to idiopathic cardiomyopathy].

Congestive heart failure (CHF) due to idiopathic cardiomyopathy is reviewed. CHF in dilated cardiomyopathy (DCM) is caused mainly by myocardial systolic dysfunction. Diuretics, angiotensin-converting enzyme (ACE) inhibitors and digitalis are the first choice drugs. ACE inhibitors have been shown to be effective in prolonging life and improving quality of life. Recently, long-term beta-blockade therapy has been shown to be useful. CHF in hypertrophic cardiomyopathy (HCM) is caused by decreased myocardial compliance. The beneficial effect of verapamil in HCM is related to improved relaxation and diastolic filing. Verapamil is also effective in relieving myocardial ischemia. Beta-blockade decreases pressure gradient and oxygen consumption. Idiopathic restrictive cardiomyopathy is a very rare disease and decreased myocardial compliance is responsible for CHF.

Adrenergic beta-Antagonists↗
PubMed1993

[The study of continuous local arterial-infusion chemotherapy with 5-FU + CDDP for patients with severely advanced HCC--for the elongation of the life-span and the improvement of QOL].

We tried continuous local arterial-infusion chemotherapy using 5-FU + CDDP with an implanted reservoir, for patients with severely advanced hepatocellular carcinoma (HCC), who had no indications for operation, PEIT or TAE. Arterial-infusion was continued for one week, followed by a one-week no-infusion period, and this treatment was repeated 1-32 times, and patients were observed for 36-549 days. Until the end of April 1993, the one-year survival rate was 61.1%. There were 3 partial remission (PR) cases, 3 progressive disease (PD) cases and the other cases showed no change (NC). Only one patient had any side effects, and all could continue as outpatients for 94.0% of the entire therapy. The patients' evaluation of QOL revealed no differences of QOL according to the length of the whole therapy, the history of rehospitalization during therapy, response to therapy, etc. But PR cases tended to show improved QOL. Therefore we considered this as effective therapy for the elongation of the life-span and the improvement of QOL.

Activities of Daily Living↗
PubMed1993

[Clinical study of continuous local arterial-infusion chemotherapy for severely advanced hepatocellular carcinoma (HCC) using reservoir].

We attempted continuous local arterial-infusion chemotherapy using reservoir for patients with severely advanced hepatocellular carcinoma (HCC), with no indications for operation, PEIT or TAE because of the advanced clinical stage, Vp-factor, and so on. Twenty-two HCC patients were given continuous arterial-infusion of 5-FU + CDDP and were observed for 36-443 days from June, 1991 to December, 1992. Until the end of 1992, we had 3 partial response (PR) cases and 3 progressive disease (PD) cases, and the other cases showed no change (NC). Except for a case in which therapy was stopped because of renal failure, no patients were disturbed by side effects, and 68.2% of the patients completed all of their therapy as outpatients. Because CDDP can amplify the effect of 5-FU in addition to its own effect as a biochemical modulator, and because continuous infusion can strengthen the effect of 5-FU and reduce the side effects of CDDP, we consider continuous local arterial-infusion of 5-FU and CDDP to be an effective therapy for severely advanced HCC. This treatment does not cure the carcinoma but helps to slow its progress and assure good QOL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Left ventricular relaxation in dilated cardiomyopathy: relation to loading conditions and regional nonuniformity.

OBJECTIVES: The purpose of the present study was to investigate how loading conditions and regional nonuniformity affect left ventricular relaxation in dilated cardiomyopathy. BACKGROUND: Left ventricular relaxation is impaired in dilated cardiomyopathy. It has been suggested that relaxation abnormality is related to loading conditions and regional nonuniformity in the diseased heart. METHODS: Left ventriculography with simultaneous pressure manometry was performed in 10 patients with dilated cardiomyopathy before and during nitroprusside infusion. Ten normal subjects served as a control group. Left ventricular hemodynamics, regional wall motion (assessed by the area method) and regional wall stress (Janz method) were analyzed. RESULTS: When compared with control subjects, the patients with dilated cardiomyopathy had a reduced left ventricular ejection fraction (p < 0.01) and prolonged relaxation time constants (p < 0.01). Left ventricular wall motion was both hypokinetic and asynchronous in the patient group. In addition, systolic regional wall stress was significantly greater, the time to peak wall stress was longer and the regional myocardial relaxation time constant was greater for each ventricular area assessed in the patient group (each p < 0.01). Administration of nitroprusside reduced left ventricular pressure and increased ejection fraction in the 10 patients with dilated cardiomyopathy. For each region, systolic regional wall stress and the time to peak wall stress decreased, and both regional hypokinesia and asynchrony lessened. These changes in loading conditions and regional nonuniformity were accompanied by an improvement in both regional and global ventricular relaxation that was significant, particularly during the early to midrelaxation phase when regional asynchrony was greatest. CONCLUSIONS: These results suggest that myocardial relaxation is sensitive to loading conditions and regional nonuniformity in dilated cardiomyopathy and that load reduction can improve both relaxation and systolic performance of the left ventricle.

Analysis of Variance↗
PubMed1992

Effects of gelsolin on human platelet cytosolic phosphoinositide-phospholipase C isozymes.

The effective resolution of human platelet cytosolic phosphoinositide-phospholipase C (PLC) revealed five distinct activity peaks by Q-Sepharose and heparin-Sepharose column chromatographies when assayed using phosphatidylinositol (PI) and phosphatidylinositol 4,5-bisphosphate (PIP2). The results of Western blotting analysis with various antibodies against PLC isozymes showed that peak-Ia (PLC-delta type), peak-Ib (PLC-gamma 1 type), and peak-IIc (PLC-beta type) and two unidentified activity peaks (PLC-IIa and PLC-IIb) were present in human platelet cytosol. A protein with guanosine 5'-3-O-(thio)triphosphate-binding activity was coeluted with the PLC-IIa and was purified to homogeneity. It exhibited 86- and 42-kDa polypeptide bands upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis which were identified as gelsolin and actin by immunostaining, respectively. Large amounts of gelsolin/actin (1:1) complex "gelsolin complex" were detected in the PLC-delta and PLC-gamma 1 fractions. The PLC-gamma 1 and the gelsolin complex were co-immunoprecipitated by the antibody raised against PLC-gamma 1. Furthermore, the partially purified bovine brain PLC-gamma 1 fraction also was found to be associated with the gelsolin complex and the association was released by the addition of 1% sodium cholate. This finding has prompted us to examine effects of the gelsolin complex and the free gelsolin on activities of the above PLC isoforms from platelet cytosol. The gelsolin complex did not affect the PIP2 hydrolyzing activities of all PLC isoforms. In contrast, the purified gelsolin inhibited distinctly PIP2 hydrolyses by PLC-Ia (delta), PLC-Ib (gamma 1), and PLC-IIa (unidentified), whereas the inhibitory effects for PLC-IIb (unidentified) and PLC-IIc (beta) were moderate. The inhibitory effect of gelsolin on PIP2-hydrolysis by PLC-gamma 1 was diminished by a large amount of PIP2 substrate. These results suggested that the inhibition of PLC by gelsolin is due to sequestration of substrate PIP2 by its competitive binding.

Animals↗
PubMed1992

Treatment of small hepatocellular carcinoma.

Of the 692 patients with hepatocellular carcinoma (HCC) who were admitted to our hospital between 1976 and 1990, 60 (8.8%) had small HCC with a maximal diameter of below 2 cm. The outcome of these 60 cases was analyzed after they had been divided into 4 groups based on the therapeutic method used: operation group (17 cases), percutaneous ethanol injection therapy (PEIT) group (20 cases), transcatheter arterial embolization (TAE) group (13 cases), and oral anticancer drug therapy (per os) group (10 cases). The 1-, 2-, 3-, 4-, and 5-year survival values obtained for the operation group (100%, 87.5%, 87.5%, 87.5%, and 87.5%, respectively) were significantly higher than those found for the per os group (P < 0.01). The best therapeutic results were achieved in the operation group. Although the follow-up period for the PEIT group was short, the 2-year survival of this group was nearly equal to that of the operation group. Whereas the duration of survival tended to increase in inverse proportion to the severity of the underlying liver cirrhosis, the survival values did not differ between solitary and multiple tumors or among the different histological grades of HCC. In this series, 20 patients died; 9 deaths (45.0%) were due to progressive disease and 3 deaths (15.0%) were attributed to hepatic failure. Because the operation group included many patients who displayed relatively good liver function, we cannot rule out the possibility that their excellent outcome may have been associated with this background factor. Therefore, further prospective investigation is necessary to compare the efficacy of various therapies in patient groups with a homogeneous background.

Aged↗
PubMed1992

The characteristics of hepatic venous flow velocity pattern in patients with pulmonary hypertension by pulsed Doppler echocardiography.

To determine the characteristic change in the Doppler hepatic venous flow velocity pattern in patients with pulmonary hypertension (PH), 21 patients with PH in sinus rhythm were examined with pulsed Doppler echocardiography. The control group included 13 subjects with chest pain syndrome and normal pulmonary arterial pressure. The hepatic vein Doppler signal was biphasic with one peak during ventricular systole (S wave) and the other in diastole (D wave). A reversed signal was recorded after contraction (A wave). The peak velocity of the A wave (Va), S wave (Vs), and D wave (Vd), the time velocity integral of these waves (VIa, VIs, and VId), the acceleration time (t-AC), and the slope of acceleration (s-AC) in the S wave were measured. Compared with controls the PH group had a higher value of Va (26.88 +/- 10.30 vs 13.41 +/- 3.69 cm/sec; p less than 0.01), VIa (2.55 +/- 1.18 vs 1.20 +/- 0.34 cm; p less than 0.01), VIa/(VIs+VId) (0.34 +/- 0.22 vs 0.14 +/- 0.06; p less than 0.01), and s-AC (372 +/- 156 vs 203 +/- 103 cm/sec2; p less than 0.01). They also had a shorter t-AC (101 +/- 32 vs 136 +/- 27 msec; p less than 0.01). There was a weak correlation between the reversed atrial flow and the right heart pressures (r = 0.43 to 0.66). Thus, the hepatic venous flow velocity pattern by Doppler echocardiography is clinically useful in evaluating pulmonary hypertension.

Adult↗