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Biomedical subjects

Jiro Nishida

Publications and source records attributed to Jiro Nishida.

14 recordsLinked to original sources
PubMed2006

Role of erythrocytes as a reservoir for ribavirin and relationship with adverse reactions in the early phase of interferon combination therapy for chronic hepatitis C virus infections.

We investigated the relationship between serum ribavirin concentrations and clearance, as well as therapeutic efficacy and adverse reactions, in 97 Japanese patients with chronic hepatitis C virus infections treated with a 6-month course of high-dose alpha2b interferon (6 million units/day) plus ribavirin (600 to 800 mg/day) combination therapy. This randomized trial showed that the saturation of ribavirin uptake after taking ribavirin capsules does not occur within a dose range of 600 to 800 mg/day, which is a standard dosage used clinically in Japan. Serum ribavirin concentrations and clearance did not correlate with sustained virological response rates. Fourteen patients discontinued therapy because of adverse reactions, and sustained virological response rates were significantly reduced by discontinuation of therapy, while dose reduction of ribavirin did not alter the therapeutic effects. Ribavirin concentrations after 1 week and ribavirin clearance were significantly correlated with discontinuation of ribavirin; however, a multiple-regression analysis revealed that only hemoglobin concentration, but not ribavirin clearance, was a significant factor for discontinuation of therapy (odds ratio, 0.514; 95% confidence interval, 0.311 to 0.85; P = 0.0095). It appears that peripheral erythrocytes may act as a reservoir for ribavirin and regulate serum ribavirin levels in the very early phase of treatment.

Adult↗
PubMed2006

Induction therapy with twice-daily interferon-beta does not improve the therapeutic efficacy of consensus interferon monotherapy for chronic hepatitis C.

We examined therapeutic superiority of induction therapy with twice-daily IFN-beta (3X2=6 million units/day) onto 6-months consensus interferon monotherapy for chronic hepatitis C. Patients were randomly assigned to monotherapy without (group I, n=16) and with induction therapy (group II, n=12). The mean age of group II was older than that of group I, and other baseline condition was not statistically significant. Sustained virological response (SVR) rates of group I and II were 81.3% (13/16) and 58.3% (7/12), respectively (p=0.365). SVR rates in patients with genotype 1b were 66.7% (4/6) and 0% (0/2, because of drop-out), and those with high viral load were 70% (7/10) and 75% (6/8) in group I and II, respectively (p=1.000). Drop-out rates during therapy were 6.3% (1/16) and 33.3% (4/12) in group I and II, respectively (p=0.176). Age less than 50 years was the only independent factor that was shown by multivariate logistic model analysis to be associated with a sustained virological response. Although randomization failed to produce and equal age distribution in the two groups in this study, our results suggest that induction therapy with twice-daily IFN-beta has no beneficial effect on the efficacy of monotherapy with consensus interferon, probably because of the higher drop-out rates and incidence of adverse reactions with induction therapy.

Female↗
PubMed2005

Ethanol-induced CXC-chemokine synthesis and barrier dysfunction in intestinal epithelial cells.

BACKGROUND: Ethanol exposure contributes to infectious complications in burn and trauma patients through a process known as "bacterial translocation." Two major factors, 1) physical disruption of the intestinal mucosal barrier and 2) suppression of immune defense, explain this phenomenon. However, little information is available concerning the immune mechanisms of ethanol-induced bacterial translocation. In this study we investigated the effect of physiological concentrations of ethanol on immune function, especially on CXC-chemokine secretion, neutrophil migration, and barrier function in the small intestine METHODS: A rat small intestinal intestinal cell line (IEC-18 cells) was exposed to 50-500 mM ethanol for 24 hr with or without IL-1 beta. Secretion of CXC chemokines (GRO/CINC-1 and MIP-2) was measured by ELISA assay, and barrier dysfunction was assessed by the apical-to-basolateral flux of HRP-dextran. Neutrophil transmigration was assessed by enzyme histochemistry (AS-D chloroesterase staining) RESULTS: Exposure to ethanol concentrations of 200 mM and over increased GRO/CINC-1 secretion, and MIP-2 secretion increased at 500 mM. Administration of ethanol in combination with IL-1 beta had no additive effect on the release of GRO/CINC-1 and MIP-2. Exposure of IEC-18 monolayers to ethanol resulted in a dose-dependent increase in permeability but IL-1 beta had no effect on barrier function. Ethanol had no effect on neutrophil migration in enzyme histochemistry analysis CONCLUSIONS: The above observations suggest that ethanol induced physical disruption of the intestine but not neutrophil transmigration is the main cause of the bacterial translocation that leads to bacteremia and endotoxemia in alcoholics.

Alcoholic Intoxication↗
PubMed2005

[A case of gastric cancer with multiple liver metastases effectively treated by hepatic arterial infusion of MMC, TS-1/CDDP therapy, and thermotherapy].

A 62-year-old man was revealed to have type 2 gastric cancer with synchronous liver metastasis. We considered liver metastasis to be a prognostic factor, and performed two courses of combination thermochemotherapy consisting of hepatic arterial infusion of MMC and TS-1 and thermotherapy. Partial response was observed in the liver metastases,but the primary lesion showed no changes; therefore, we performed four courses of combination thermochemotherapy consisting of TS-1/CDDP therapy and thermotherapy. By the end of three courses of this therapy,the primary lesion had cicatrized,and endoscopic biopsy revealed no cancer cells. These results suggest that gastric cancer,in which liver metastasis is considered to be a prognostic factor,can be effectively treated by combination therapy with hepatic arterial infusion therapy, followed by thermochemotherapy for the primary lesion.

Adenocarcinoma↗
PubMed2004

Pioglitazone prevents alcohol-induced fatty liver in rats through up-regulation of c-Met.

BACKGROUND & AIMS: Treatment of steatosis is important in preventing development of fibrosis in alcoholic liver diseases. This study aimed to examine if pioglitazone, an antidiabetic reagent serving as a ligand of peroxisome proliferator-activated receptor gamma (PPAR gamma), could prevent alcoholic fatty liver. METHODS: Rats fed with an ethanol-containing liquid diet were given the reagent at 10 mg/kg per day intragastrically for 6 weeks. Hepatic genes involved in actions of the reagent were mined by transcriptome analyses, and their changes were confirmed by real-time polymerase chain reaction and Western blotting analyses. The direct effects of pioglitazone on primary-cultured hepatocytes were also assessed in vitro. RESULTS: Pioglitazone significantly attenuated steatosis and lipid peroxidation elicited by chronic ethanol exposure without altering insulin resistance. Mechanisms for improving effects of the reagent appeared to involve restoration of the ethanol-induced down-regulation of c-Met and up-regulation of stearoyl-CoA desaturase (SCD). Such effects of pioglitazone on the c-Met signaling pathway resulted from its tyrosine phosphorylation and resultant up-regulation of the apolipoprotein B (apoB)-mediated lipid mobilization from hepatocytes through very low-density lipoprotein (VLDL) as well as down-regulation of sterol regulatory element binding protein (SREBP) -1c and SCD levels and a decrease in triglyceride synthesis in the liver. CONCLUSIONS: Pioglitazone activates c-Met and VLDL-dependent lipid retrieval and suppresses triglyceride synthesis and thereby serves as a potentially useful stratagem to attenuate ethanol-induced hepatic steatosis.

Alcohol Drinking↗
PubMed2004

Tongue metastasis as an initial presentation of a lung cancer.

Metastasis to the tongue seldom occurs, and lingual metastasis as an initial sign of cancer occurs even less frequently. We report a case of lung cancer in which the patient's initial symptom was related to the tongue metastasis. A 63-year-old man had a submucosal tumor on the left posterolateral aspect of the tongue and a biopsy specimen of the tongue tumor showed poorly differentiated squamous cell carcinoma. A chest X-ray showed a mass in the right lung and cytological examination of the specimen obtained by bronchial brushing showed poorly differentiated squamous cell carcinoma, whose appearance was similar to that of the tongue. Based on these findings, the tongue lesion was diagnosed a metastatic tumor from the lung cancer. The patient received radiation therapy combined with systemic chemotherapy, however, he died 5 months after the diagnosis of lung cancer. An autopsy revealed a lung cancer in the right lower lobe with metastatic tumors in the tongue, right middle lobe, left upper lobe, liver, adrenal gland, pericardium, heart, and subcutaneous tissues. No other possible primary cancer that may have been the cause of the metastases was identified.

Antineoplastic Agents↗
PubMed2003

Hepatic microvascular development in relation to the morphogenesis of hepatocellular plates in neonatal rats.

The development of hepatic microvascular heterogeneity after birth, and its temporal relationship to the development of parenchymal cell plates have received little attention. As a result, the morphogenesis of some of the parameters contributing to this heterogeneity in suckling and weaned rats was studied as a function of time between postpartum days 4 and 30 using in vivo light microscopic, electron microscopic, and immunocytochemical methods. During the early suckling period, the sinusoid network is highly anastomotic, with little evidence of zonation, and the parenchymal cell plates contain multiple cells and are irregularly arranged throughout the lobule. Sinusoidal endothelial fenestration is sparse at 4 days, but phagocytic Kupffer cell (KC) function already exists and exhibits zonal heterogeneity, with more cells located in the periportal zone. With increasing age, endothelial fenestrae increase and organize as sieve plates. Widened centrilobular radial sinusoids form through a loss ("drop-out") of intersinusoidal sinusoids (ISS). Concomitantly, the associated cell plates straighten and become one cell thick. Hepatocyte DNA synthesis and mitosis are higher in the periportal zone, which retains thickened cell plates and anastomotic sinusoids. The centrilobular sinusoids may widen to accommodate the increased volume of blood that results from the loss of ISS as well as the increased numbers of periportal sinusoids containing flow that feed these vessels. KC phagocytic activity increases during the suckling period concomitant with an increase of gut-derived endotoxin in the portal blood, which suggests that the KCs may be releasing mediators that affect sinusoid diameter, blood flow, endothelial fenestration, and perhaps parenchymal growth either directly or through the stimulation of growth factors.

Age Factors↗
PubMed2002

Treatment of bronchorrhea by corticosteroids in a case of bronchioloalveolar carcinoma producing CA19-9.

A case of gastrointestinal cancer-associated antigen (CA19-9)-positive bronchioloalveolar carcinoma accompanied by bronchorrhea and respiratory failure successfully treated with corticosteroids is reported. The patient was treated with pulse methylprednisolone at a dose of 1,000 mg/day for three days, followed by oral prednisolone (60 mg/day). Within 2 days, the sputum volume decreased from >100 ml/day to 20 ml/day and it was finally controlled to 0-10 ml/day. The reduction in the sputum volume was associated with alleviation of dyspnea and hypoxemia. The levels of CA19-9 in the serum and the sputum were extremely high and an immunocytochemical study showed that the tumor cells were stained by CA19-9 antibody. This case demonstrates the therapeutic value of corticosteroids in the treatment of bronchorrhea in subjects with bronchioloalveolar carcinoma.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMedDate not supplied

Additive therapeutic effects of the liver extract preparation mixture adelavin-9 on interferon-beta treatment for chronic hepatitis C.

BACKGROUND/AIMS: We previously reported that intravenous interferon-beta administration was effective in treating patients with chronic hepatitis C and that there was no significant correlation between the response to therapy and host in vitro immunoglobulin production. The aims of this study were to evaluate the additive effect of a liver extract preparation and flavin adenine dinucleotide mixture and to reevaluate the correlation. METHODOLOGY: 65 patients with chronic hepatitis C received intravenously 6 million units of interferon-beta and 2 mL of a liver extract preparation and flavin adenine dinucleotide mixture. The results of this study were compared with those of our previous study, on interferon-beta monotherapy in 91 patients with chronic hepatitis C. In addition, peripheral blood mononuclear cells were obtained before interferon-beta administration and cultured. Immunoglobulin concentrations in their supernatants were measured and the correlation with the interferon response was evaluated. RESULTS: The virological end-of-treatment or sustained response occurred in 49 of 58 cases (84.5%), and 16 of 58 cases (27.6%), respectively. Biochemical end-of-treatment or sustained responses occurred in 22 of 58 cases (37.9%), and 30 of 58 cases (51.7%), respectively. These response rates were higher than those reported in our previous study of interferon monotherapy. Monovariate analysis indicated that the use of the liver extract preparation and flavin adenine dinucleotide mixture was a significant predictor of the virological end-of-treatment response and the sustained biochemical response, but by multivariate analysis these relationships were not significant. Immunoglobulin production was not correlated with the virological and biochemical responses. CONCLUSIONS: This study indicated that combination therapy with intravenous interferon-beta and the liver extract preparation and flavin adenine dinucleotide mixture was more effective than intravenous interferon-beta monotherapy. However, no correlation between the interferon response and in vitro immunoglobulin production was observed.

Adult↗