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Biomedical subjects

T Kumada

Publications and source records attributed to T Kumada.

At least 73 records · Page 4Linked to original sources
PubMed1996

Long-term administration of natural interferon-alpha in patients with chronic hepatitis C: relationship to serum RNA concentration, HCV-RNA genotypes, histological changes and hepatitis C virus.

To virologically assess the efficacy of interferon therapy in chronic hepatitis C, either 5 or 10 MU/day natural interferon-alpha (IFN alpha) was administered to 57 patients with chronic hepatitis C for 38 weeks. A complete and sustained response (CR-SR), as evidenced by the absence of serum hepatitis C virus (HCV)-RNA during the administration period and at 6 months after the final administration of IFN alpha and normal GPT level at 6 months after final administration, occurred in 42.6% (23/54) of subjects. Liver tissue was histologically evaluated using the histological activity index (HAI) score before and after the administration period. In CR-SR cases, significant improvements (P < 0.01) occurred in periportal necrosis, intralobular necrosis, portal inflammation and total score. A comparison, by HCV genotypes, revealed that CR-SR occurred in 60% (9/15) of subjects with type 2a and 30.3% (10/33) of subjects with type 1b. A comparison by virus concentration revealed that CR-SR occurred in 71.4% (15/21) of those subjects having a virus concentration of < 10(5) copies/mL, but in only 24.2% (8/33) of those having a virus concentration of > 10(5) copies/mL. Analysis by a multiple logistic model revealed a strong correlation between the therapeutic effect of interferon therapy and the pre-administration virus concentration (P = 0.0061) and genotype (P = 0.0015). These results suggest that the pre-administration virus concentration and genotype are both key factors affecting the therapeutic effect of interferon therapy in chronic hepatitis C and that the therapeutic effect of interferon is satisfactorily high, irrespective of virus concentration, in subjects with type 2a HCV, but varies depending on virus concentration in subjects with type 1b.

Aged↗
PubMed1996

Estimation of usefulness of N-butyl-2-cyanoacrylate-lipiodol mixture in transcatheter arterial embolization for urgent control of life-threatening massive bleeding from gastric or duodenal ulcer.

We estimated the usefulness of a mixture of N-butyl-2-cyanoacrylate (NBCA) with lipiodol for transcatheter arterial embolization (TAE) used to control massive bleeding from gastric or duodenal ulcer. Thirty patients who had gastric or duodenal ulcers and massive bleeding that was uncontrollable by endoscopic procedures were included in this study. All patients were subjected to TAE (without NBCA in 23 and with NBCA in seven patients). Coils and/or gelfoam were also used. The achievement of haemostasis, occurrence of rebleeding and the time taken for TAE were compared between patients who received TAE without and with NBCA. Eighteen of 23 patients (78.3%) who received TAE without NBCA and six of seven patients (85.7%) who underwent TAE with NBCA achieved complete haemostasis without rebleeding. The time for TAE was significantly shorter in patients who received NBCA compared with those who did not (P = 0.0095). TAE using NBCA or a combination of NBCA and coils achieved a rapid, complete embolization regardless of vascular distribution or arterial diameter. Thus NBCA is considered to be useful as a secondary embolization material in TAE that is urgently conducted to control massive bleeding from gastric or duodenal ulcers.

Adult↗
PubMed1996

[The clinical evaluation of hepatic arterial infusion chemotherapy in patients with liver metastases from colorectal cancer employing an implanted port system].

Between 1986 and 1994, 66 patients with unresectable liver metastases from colorectal cancer were treated by repeated hepatic arterial infusion chemotherapy employing an implantable port system. In this study, 44 patients who received intermittent hepatic arterial infusion of high dose 5-FU (1000mg/m2) were analysed according to a response rate, survival rates, developments of extrahepatic lesions, periods of hepatic arterial infusion, and the rates at home. Two cases (4.5%) achieved a complete response (CR) and 27 cases (61.4%) a partial response (PR). The overall one-year and two-year survival rates were 56.7% and 37.8% respectively. The 50% survival time for all patients was 17.2 months. During the course of observation, extrahepatic lesions developed in 16 of the 39 patients (41.0%) and many responders died due to deterioration of extrahepatic lesions. The over all rates at home were more than 85%. Hepatic arterial infusion of the 5-FU at 1000mg/m2 every week showed a high response rate in colorectal cancer patients with hepatic metastases, and the responders showed a low rate of death due to the hepatic metastases. However, in many patients the prognosis-determining-factor was extrahepatic lesions. Thus, countermeasures were necessary for extrahepatic lesions.

Aged↗
PubMed1996

Effect of daily administration period of natural alpha-interferon in patients with chronic hepatitis C.

OBJECTIVE: A randomized, controlled trial was performed to study the effect of the period of daily administration of interferon therapy in patients with chronic hepatitis C. PATIENTS AND METHODS: Sixty-three patients were administered a total dose of 480 MU of natural alpha-interferon, 6 MU each day. In 32 cases, interferon was given daily for 2 wk, followed by intermittent administration (three times a week) for 22 wk. The other 31 patients received daily administration for 8 wk, followed by intermittent administration (twice a week) for 12 wk. The responses were based on the normalization of ALT and the clearance of hepatitis C virus. RESULTS: Although ALT normalized in 37 patients during the administration of interferon, it relapsed after the end of interferon therapy in 20 patients. The other 17 patients achieved sustained normalization of ALT and clearance of hepatitis C virus RNA. Responses did not differ according to the administration period of interferon. CONCLUSIONS: Prolonged daily administration did not improve the responses to interferon therapy when the total dose was the same.

Alanine Transaminase↗
PubMed1995

Antigen-mediated phospholipase D activation in rat basophilic leukemia (RBL-2H3) cells: possible involvement of calcium/calmodulin.

The differential implication of protein kinase C (PKC) isozymes in antigen- or PMA-induced phospholipase D (PLD) activation was investigated in rat basophilic leukemia (RBL-2H3) cells. In [3H]oleic acid-labeled cells, both antigen (100 ng/ml) and phorbol 12-myristate 13-acetate (PMA) (100 nM) produced a specific product of PLD activation, [3H]phosphatidylbutanol (PBut) in the presence of butanol. Pretreatment of cells with a selective PKC inhibitor, Ro31-8425 (1-5 microM) inhibited PMA-stimulated PLD activity by 85%. In contrast, the antigen-stimulated PLD activity was much less sensitive to the inhibitor. RBL-2H3 cells express PKC alpha, beta, delta, epsilon and zeta isozymes and down-regulation of PKC by exposure to PMA (20 nM) for 1-2 h caused rapid decrease in PKC alpha and beta isozymes, leaving PKC delta, epsilon and zeta isozymes intact. Apparent decreases in the levels of PKC alpha and beta to about 50% were observed after adding 20 nM PMA for 1 h, when PMA-stimulated PLD activity was inhibited by up to 70%. Decrease in antigen-stimulated PLD activity was evident after 2 h PMA-treatment, when PKC alpha and beta decreased by nearly 70%. These results suggest that in the antigen-mediated PLD pathway PKC may be implicated but not play such a great role as PMA-stimulated pathway which is mediated through PKC alpha or beta. Then, we have examined the involvement of calcium/calmodulin (CaM) in PLD activation by antigen, since the antigen-stimulated PLD activation showed the absolute requirement for extracellular calcium. Preincubation of RBL-2H3 cells with a CaM antagonist W-7 (20 microM) inhibited the antigen-stimulated PLD activity by 90%, but W-5, a chlorine-deficient analogue of W-7 that only weakly interact with CaM, caused little inhibitory effect. Another non-specific CaM antagonist, trifluoperazine (TFP) also inhibited PLD activation. These results suggest that calcium/CaM may be involved in the antigen-stimulated PLD activation.

Animals↗
PubMed1995

HCV RNA monitoring for tailored regimens of interferon therapy in hepatitis C.

Sustained non-viraemia is prerequisite for a virological cure of hepatitis C virus (HCV) disease. We monitored serum HCV RNA in our patients during interferon therapy and for 6 months of follow-up. The rate of sustained responders (RNA-negative at the end of follow-up) differed significantly by whether or not RNA became sero-negative within 24 weeks of the initiation of therapy (71% vs 7%); and also by whether or not the RNA-seronegativity lasted for 12 weeks during therapy (88% vs 11%). Thus, by monitoring viraemia in individual patients, we can tailor the duration of therapy and minimize waste of interferon.

Follow-Up Studies↗
PubMed1995

Transcatheter arterial embolization for massive bleeding from duodenal ulcers not controlled by endoscopic hemostasis.

BACKGROUND AND STUDY AIMS: We evaluated the efficacy of transcatheter arterial embolization (TAE) in patients in whom endoscopic hemostasis of a massively bleeding duodenal ulcer failed. PATIENTS AND METHODS: TAE was performed in 11 patients with endoscopically uncontrollable massively bleeding duodenal ulcers, and the results and long-time outcome were studied. Two additional cases of failed endoscopic hemostasis were treated surgically without TAE. The entire group of 13 patients represented 5% of endoscopically treated duodenal ulcers and 0.6% of all cases with upper gastrointestinal bleeding who underwent emergency endoscopy (n = 2073). All but one of these 13 patients had concomitant disease. RESULTS: Arteriograms performed before TAE revealed extravasation of contrast material around the gastroduodenal artery (GDA), the anterior superior pancreaticoduodenal artery (ASPD), or the posterior superior pancreaticoduodenal artery (PSPD) in six of 11 cases. We failed to stop the bleeding in one patient, in whom only the common hepatic artery side of the GDA bleeding site was embolized; this patient died. TAE was successful in the other ten patients, in whom the long stretch of the GDA, including the ASPD and PSPD, was embolized around the bleeding site. Two surgically treated patients died within a week. CONCLUSIONS: Our findings indicate that TAE may induce hemostasis in 90% of patients with serious concomitant diseases who have endoscopically uncontrollable massive bleeding from duodenal ulcers.

Aged↗
PubMed1995

Clearance of serum hepatitis C virus RNA after interferon therapy in relation to virus genotype.

The effect of recombinant interferon-alfa on serum HCV RNA levels in Japanese patients with chronic hepatitis C was investigated. At 24 weeks of treatment, 41 (32.5%) of 126 patients lost HCV RNA from serum, and aminotransferases were normalized in 31 (75.6%) of these 41 cases. HCV genotypes were categorized into four types (Type I, II, III, IV); the frequencies among the patients were: Type I: 0%, Type II: 70.6%, Type III: 20.6%, and Type IV: 6.3%. At the end of the 24-week treatment, HCV RNA levels were remarkably decreased in Type III patients and became undetectable in 18 (69.2%) of 26. In contrast, only 18 (20.2%) of 89 patients with Type II and two of eight with Type IV lost HCV RNA from sera. The relation between HCV genotype (Type III) and response to IFN therapy was also confirmed using a logistic regression model. HCV genotype seems to be an important factor in determining the response to IFN in patients with chronic hepatitis C.

Alanine Transaminase↗
PubMed1995

Serum levels of soluble interleukin-2 receptor in chronic hepatitis C treated with interferon-alpha.

BACKGROUND: Serum levels of soluble interleukin-2 receptor (sIL-2R) seem to serve as a marker for the activation of T lymphocytes. The aim of this study was to evaluate the clinical significance of such levels in patients with chronic hepatitis C (CHC) treated with interferon. METHODS: We measured serum levels of sIL-2R in 37 patients with CHC before and after treatment with recombinant interferon-alpha. Serum receptor levels were then compared with the response of the hepatitis C virus (HCV)-RNA level in serum after interferon. RESULTS: Receptor levels were significantly higher in the patients with chronic persistent hepatitis and chronic active hepatitis than in normal controls (p < 0.01). There was a weak correlation between serum sIL-2R and alanine aminotransferase (ALAT) levels (r = 0.14, p = 0.010). Patients were then classified into three groups on the basis of the effect of interferon treatment on HCV-RNA levels in serum: sustained response (SR; n = 21), non-sustained response (NSR; n = 14), and nonresponse (NR; n = 2). Before and during interferon treatment the serum sIL-2R level remained increased in the SR group and in the combined groups with NSR or NR. However, after interferon was withdrawn, the serum sIL-2R decreased in the SR group but remained significantly increased in the combined response group (p < 0.01-0.05). CONCLUSION: This finding seems to reflect the disappearance of HCV-RNA from the serum of the patients with an SR, and monitoring of sIL-2R levels may therefore be of value as an adjunct to the measurement of serum ALAT and HCV-RNA in evaluating the response to the interferon therapy for CHC.

Adult↗
PubMed1995

[Clinical evaluation of a recurrent mode after treatment in patients with small hepatocellular carcinoma].

A total of 96 patients with small hepatocellular carcinoma (HCC) with a maximal diameter of below 2 cm were analyzed according to recurrent factors and recurrent modes after the first treatment. In this study, recurrences were divided into two groups based on the style of recurrences provisionally: intrahepatic metastases (IM, 35 cases) and multicentric recurrences (MC, 22 cases). In patients with IM, the majority of recurrences were observed within 2 years after the first treatment and the primary HCC lesions had strong relation to the degrees of malignancy. On the other hands, there were no association with recurrent intervals and the degrees of malignancy, although the recurrent rate was high in patients with anti-HCV in MC group. The prognosis after the second treatment in MC group was superior to that in IM group (p < 0.05). These results indicate MC group have a good prognosis if early detection and the second accurate treatment are performed.

Aged↗
PubMed1995

[Effects of antiallergic drug, pemirolast potassium on phospholipase D activation in antigen-stimulated rat basophilic leukemia (RBL-2H3) cells].

An anti-allergic drug, permirolast potassium (TBX), inhibited antigen (Ag)-induced phospholipase D (PLD) activation in rat basophilic leukemia (RBL-2H3) cells. The concentration-dependent inhibitory profile for Ag-induced PLD activation was parallel to those for secretory response and inositol phosphate formation. In contrast, TBX had no effect on PLD activation caused by calcium ionophore A23187 or phorbol myristate acetate. These results suggest that TBX inhibits Ag-induced PLD activation by interfering with the signal transduction pathway upstream of Ca2+ mobilization and protein kinase C activation.

Animals↗
PubMed1995

Effects of an antiallergic drug, pemirolast potassium on tyrosine phosphorylation and map kinase activation in antigen-stimulated rat basophilic leukemia (RBL-2H3) cells.

Aggregation of high affinity IgE Fc receptors (Fc epsilon RI) on RBL-2H3 cells results in tyrosine phosphorylation of 33-, 42-, 44-, 72-, 80-, 90-, 125-kDa proteins. The 42 and 44 kDa proteins were identified as mitogen-activated protein (MAP) kinases with immunoblotting of anti-MAP kinase antibody. The effects of an antiallergic drug, pemirolast potassium (TBX) on Ag-induced protein tyrosine phosphorylation and MAP kinase activation were investigated. When RBL-2H3 cells were stimulated with Ag in the presence of TBX, tyrosine phosphorylation of three proteins (33, 42 and 44 kDa) was inhibited concentration-dependently (0.1-10 micrograms/ml). Inhibition of Ag-induced tyrosine phosphorylation of 33 kDa protein, which could be a beta subunit of Fc epsilon RI, suggests that TBX may prevent the activation of Fc epsilon RI. TBX suppressed activation of MAP kinases (42 and 44 kDa) in response to Ag as well as phorbol myristate acetate (100 nM) or calcium ionophore A23187 (500 nM), implying that the drug acts on signal transduction component(s) between the second messengers and MAP kinases. However, TBX had no effects on protein tyrosine phosphorylation and MAP kinase activation in MC3T3-E1 osteoblastic cells. These results indicate that TBX may affect Fc epsilon RI and also may act as a step distal of Ca2+ mobilization and protein kinase C activation leading to MAP kinase activation in RBL-2H3 cells.

Animals↗
PubMed1995

[The pharmacokinetics of the glycyrrhizin and glycyrrhetic acid after intravenous administration of glycyrrhizin for the patients with chronic liver disease caused by type C hepatitis virus].

Glycyrrhizin had been used widely for the patients with chronic liver disease. We examined the pharmacokinetics of the glycyrrhizin and glycyrrhetic acid in the blood stream after intra-venous administration of glycyrrhizin. The stream concentration of glycyrrhizin in the patients of liver cirrhosis tend to be kept higher than that of chronic hepatitis but there were no significant difference between them except for after a half hour from the administration. There was negative correlation between ICG R15 and the speed of excretion of glycyrrhizin from the serum. On the other hand, the concentration of the glycyrrhetic acid was kept higher in the patients with liver cirrhosis than that of chronic hepatitis, but there were no significant difference between them except for after a half hour from the administration. These findings suggested that the accumulation of glycyrrhizin and glycyrrhetic acid in the patients of liver cirrhosis can be seen by long term administration.

Aged↗
PubMed1995

[A case of heterochronic bilateral renal infarction].

A 57-year-old man was admitted with aching pain in his left frank. Left renal infarction was revealed by CT scan and arteriogram. Intra-arterial thrombolytic therapy was performed, and resulted in a recanalization of the occluded artery and elimination of frank pain, but residual stenosis was recognized. At 27 hours after the onset of left renal infarction, in spite of the systemic anti-coagulant and thrombolytic therapy to prevent the recurrence of the thrombosis, right renal infarction occurred. Immediate intra-arterial thrombolytic therapy for right renal infarction was performed successfully. Subsequently the serum creatinine level increased from 0.8-0.9 to 1.2-1.3 mg/dl due to the functional loss of the left kidney, which was confirmed by follow-up renoscintigraphy. Conservative intra-arterial thrombolytic therapy seems to be the most effective treatment for renal infarction, but left renal salvage failed due to the prolonged time of occlusion and residual stenosis. Also, catheterization for diagnosis and therapy or thrombolytic therapy itself may induce an additional infarction.

Creatinine↗
PubMed1994

Potent activation of phospholipase D by phenylarsine oxide in rat basophilic leukemia (RBL-2H3) cells.

A putative protein tyrosine phosphatase inhibitor, phenylarsine oxide (PAO), potentiated phospholipase D (PLD) activity concentration-dependently in [3H] oleic acid-labeled rat basophilic leukemia (RBL-2H3) cells without significant increase in phosphatidylinositol-specific phospholipase C (PI-PLC) activity. Although PAO induced tyrosine phosphorylation of several proteins, both PAO-induced PLD activation and tyrosine phosphorylation were not affected by a protein tyrosine kinase inhibitor, genistein. Another tyrosine kinase inhibitor, herbimycin A, prevented the PAO-induced PLD stimulation but had no effect on protein tyrosine phosphorylation. However, depletion of protein kinase C (PKC) greatly reduced PAO-stimulated PLD activity. These results indicate that PKC but not tyrosine kinase may be involved in PAO-mediated PLD activation.

Animals↗
PubMed1994

Phosphoinositide hydrolysis in Ki-ras-transformed fibroblasts stimulated by platelet-derived growth factor and bradykinin.

Signal transduction in response to platelet-derived growth factor (PDGF)-BB and bradykinin (BK) have been examined by measuring inositol polyphosphate formation in NIH3T3 fibroblast and v-Ki-ras-transformed NIH3T3 fibroblast (DT). The PDGF-induced inositol polyphosphate formation in NIH3T3 was greater than that in DT cells, in which autophosphorylation of PDGF receptor and tyrosine phosphorylation of phospholipase C (PLC)-gamma 1 were suppressed when examined by immunoblotting with anti-phosphotyrosine antibody. On the other hand, BK-stimulation produced a much higher level of inositol polyphosphate in DT cells which have a greater number of BK receptors. These results indicate that in Ki-ras transformed cells the decrease (caused by PDGF) and the increase (caused by BK) in phosphoinositide hydrolysis are due to the defective autophosphorylation of PDGF receptors leading to a reduction in PLC-gamma 1 tyrosine phosphorylation and the overexpression of BK receptors, respectively.

3T3 Cells↗