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Biomedical subjects

Michio Sata

Publications and source records attributed to Michio Sata.

At least 145 records · Page 8Linked to original sources
PubMed2003

A pilot study of eicosapentaenoic acid therapy for ribavirin-related anemia in patients with chronic hepatitis C.

One of the major side effects of ribavirin/interferon alpha combination therapy for chronic hepatitis C is hemolytic anemia. One of the causes of hemolytic anemia is considered to be decreasing deformability of erythrocytes resulting from the accumulation of phosphorylated ribavirin in erythrocytes. The administration of eicosapentaenoic acid (EPA), which has a wide variety of pharmacological actions, increases the deformability of erythrocytes. We conducted an uncontrolled pilot study of EPA therapy for patients with ribavirin-related anemia. Six patients with chronic hepatitis C, who had developed anemia while receiving combination therapy, were treated with an oral ethyl ester of EPA (1800 mg/day) for two months. The hemoglobin level of all six patients increased following EPA therapy. The mean hemoglobin level significantly increased from 10.8 g/dl to 11.4 g/dl one month after therapy was initiated (P<0.05), and this level was obtained again one month later (11.5 g/dl). None of the patients developed an adverse reaction. These findings suggest that EPA has a beneficial effect in patients with ribavirin-related anemia. Further study is required to confirm our results.

Adult↗
PubMed2003

Predictive factors for remission and death in 73 patients with autoimmune hepatitis in Japan.

The prognosis of patients with autoimmune hepatitis (AIH) has not been clearly defined. The aim of this study was to define the prognostic factors of AIH in a population with long-term follow-up in Japan. Seventy-three patients who were diagnosed as having type 1 AIH between January, 1972 - August, 1999 were enrolled in this study. Initial treatment included prednisolone (PSL) (n=62), other drug regimens (n=7), and none (n=4). We examined the relation between several factors obtained at diagnosis in relation to disease activity found at the final observation point (January, 2000 - April, 2000). Multivariate logistic regression and Cox regression were used for statistical analysis. During the observation period, 8 patients died of the following: hepatic failure (n=4), hepatocellular carcinoma (n=1), severe infection (n=1), and unknown causes (n=2). At the end point, the number of patients in complete remission was 13, those with a normal alanine aminotransferase (ALT) level requiring some treatment was 35, and those with an abnormal ALT level despite medication was 17. Factors related to remission were total bilirubin (TB) (Odds ratio, 0.87), and immunoglobulin G (IgG) (Odds ratio, 1.00). Factors related to death were the aspartate aminotransaminase (AST)/ALT ratio (Odds ratio, 11.67) and response to initial PSL regimen (Odds ratio, 0.03). The results of this study show an importance of achieving a good PSL response at onset, and that initial TB, the AST/ALT ratio, and IgG levels are useful for therapeutic strategy.

Adult↗
PubMed2003

Treatment of ulcerative colitis patients by long-term administration of germinated barley foodstuff: multi-center open trial.

Germinated barley foodstuff (GBF), which mainly consists of dietary fiber and glutamine-rich protein, is a prebiotic for ulcerative colitis (UC). In our previous study, we carried out a clinical trial of GBF with mildly to moderately active UC patients and showed that GBF treatment was able to attenuate the symptoms of UC in a relatively short-term. The aim of this study was to investigate the efficacy of long-term administration of GBF in the treatment of UC in a multi-center open trial. Twenty-one patients with mildly to moderately active UC received 20-30 g of GBF for 24 weeks in an open-label protocol while baseline treatments (5-amino-salicyrate compounds and/or steroids) were continued. The response to the GBF treatment was evaluated using a clinical scoring and after 24 weeks of observation, the GBF group showed a significant decrease in clinical activity index (especially, the degree of visible blood in stools and the presence of nocturnal diarrhea) compared with the control group (p<0.05). No side effects related to GBF were observed. In conclusion, GBF can reduce the clinical activity of UC over long-term as well as short-term administration. Nutraceutical GBF therapy may have a place in long-term management of UC, but controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.

Adult↗
PubMed2002

Activation of STAT3 by the hepatitis C virus core protein leads to cellular transformation.

The signal transducer and activator of transcription (STAT) family proteins are transcription factors critical in mediating cytokine signaling. Among them, STAT3 is often constitutively phosphorylated and activated in human cancers and in transformed cell lines and is implicated in tumorigenesis. However, cause of the persistent activation of STAT3 in human tumor cells is largely unknown. The hepatitis C virus (HCV) is a major etiological agent of non-A and non-B hepatitis, and chronic infection by HCV is associated with development of liver cirrhosis and hepatocellular carcinoma. HCV core protein is proposed to be responsible for the virus-induced transformation. We now report that HCV core protein directly interacts with and activates STAT3 through phosphorylation of the critical tyrosine residue. Activation of STAT3 by the HCV core in NIH-3T3 cells resulted in rapid proliferation and up-regulation of Bcl-XL and cyclin-D1. Additional expression of STAT3 in HCV core-expressing cells resulted in anchorage-independent growth and tumorigenesis. We propose that the HCV core protein cooperates with STAT3, which leads to cellular transformation.

3T3 Cells↗
PubMed2002

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: analysis of 48 cases.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is extremely poor. The aim of this study was to elucidate the efficacy of hepatic arterial infusion chemotherapy (HAIC) for patients with advanced HCCs. METHODS: Forty-eight HCC patients with PVTT were treated by HAIC via a subcutaneously implanted injection port. Of these, 14 had PVTT in the second portal branch and 34 patients had PVTT in the first portal branch or in the main portal trunk. One course of chemotherapy consisted of daily cisplatin (7 mg/m(2) for 1 hour on Days 1-5) followed by 5-fluorouracil (170 mg/m(2) for 5 hours on Days 1-5). Patients were scheduled to receive four serial courses of HAIC. Responders were defined as having either a complete response (CR) or partial response (PR) and nonresponders were defined as exhibiting stable disease or progressive disease. The prognosis after HAIC and factors related to survival were analyzed. RESULTS: Following HAIC, 4 and 19 patients exhibited a CR and PR, respectively (response rate = 48%). The 1, 2, 3, and 5-year cumulative survival rates of 48 patients treated with HAIC were 45%, 31%, 25%, and 11%, respectively. Median survival periods for 23 responders and 25 nonresponders were 31.6 (range, 8.3-76.9) months and 5.4 (1.9-29.0) months, respectively. Therapeutic effect (P < 0.001) and hepatic reserve capacity (P = 0.021) were identified as significant prognostic factors by univariate analysis. Multivariate analysis identified only therapeutic effect as being significantly related to survival. CONCLUSIONS: HAIC using low-dose cisplatin and 5-fluorouracil may be a useful therapeutic option for patients with advanced HCC with PVTT. HCC patients with PVTT who respond to HAIC could certainly have survival benefits.

Aged↗
PubMed2002

Treatment of ulcerative colitis by feeding with germinated barley foodstuff: first report of a multicenter open control trial.

BACKGROUND: Germinated barley foodstuff (GBF) is a prebiotic foodstuff that effectively increases luminal butyrate production by stimulating the growth of protective bacteria. In the first pilot study, GBF has been shown to reduce both clinical activity and mucosal inflammation in ulcerative colitis (UC). The aim of this study was to investigate the efficacy of GBF in the treatment of UC in a multicenter open control trial. METHODS: Eighteen patients with mildly to moderately active UC were divided into two groups using a random allocation protocol. The control group (n = 7) were given a baseline anti-inflammatory therapy for 4 weeks. In the GBF-treated group (n = 11), patients received 20-30 g GBF daily, together with the baseline treatment, for 4 weeks. The response to the treatments was evaluated clinically and endoscopically. Fecal microflora were also analyzed. RESULTS: After 4 weeks of observation, the GBF-treated group showed a significant decrease in clinical activity index scores compared with the control group (P < 0.05). No side effects related to GBF were observed. GBF therapy increased fecal concentrations of Bifidobacterium and Eubacterium limosum. CONCLUSIONS: Oral GBF therapy may have the potency to reduce clinical activity of UC. We believe that these results support the use of GBF administration as a new adjunct therapy for UC.

Adult↗
PubMed2002

Intestinal microflora as a therapeutic target in inflammatory bowel disease.

Although the causes of inflammatory bowel disease (IBD) remain incompletely understood, increasing evidence implicates intestinal microflora in the pathogenesis of these disorders. Alteration of intestinal flora therefore may offer a plausible therapeutic approach. Although recent data support a potential therapeutic role for probiotics and prebiotics in patients with IBD, such treatments need to be further assessed by large, double-blind controlled trials. A better understanding of the intestinal microflora and the mechanisms of their action may help us to develop more effective treatment for IBD.

Biopsy, Needle↗
PubMed2002

Propranolol ameliorates thrombocytopenia in patients with cirrhosis.

BACKGROUND: Propranolol causes splanchnic arterial vasoconstriction owing to the unopposed alpha vasoconstriction resulting from the blockade of beta-2 adrenoceptors. It is therefore hypothesized that this drug may cause vasoconstriction in the splenic arterial circulation and, thus, modify the manifestations of hypersplenism, such as thrombocytopenia. The aim of the present study was to test this hypothesis. METHODS: Nineteen patients with cirrhosis and thrombocytopenia (fewer than thrombocytes 7 x 10(4)/mm3) were include. The subjects of the study. All of them were studied in the morning after an overnight fast. To evaluate splenic arterial hemodynamics, the pulsatility index was measured by Doppler ultrasonography. Platelet counts and platelet-associated immunoglobulin G levels were also recorded. The subjects were then randomized to receive propranolol (n = 10) or placebo (n = 9). The measurements were repeated after 1 week of propranolol or placebo administration. The dose of propranolol was determined so that a 20% to 25% reduction in heart rate was achieved. RESULTS: Placebo administration caused no significant changes in splenic artery hemodynamics. In contrast, propranolol administration significantly increased the intra splenic artery pulsatility index (from 1.10+/-0.06 to 1.24+/-0.08; P < 0.01). Placebo administration caused no significant changes in the platelet count. In contrast, propranolol administration significantly increased the platelet count (from 4.5+/-0.3 to 6.1+/-0.73 x 10(4)/mm3; P < 0.05). Furthermore, the change in platelet count was significantly correlated with either the change in extrasplenic artery pulsatility index (r = 0.78, P < 0.05) or the change in intrasplenic artery pulsatility index (r = 0.78, P < 0.01). Platelet-associated immunoglobulin G levels were not modified in either of the two groups. CONCLUSIONS: Propranolol ameliorates thrombocytopenia in patients with cirrhosis. This effect may be caused mainly by hemodynamic changes in the spleen, rather than being caused by immunological mechanisms.

Adrenergic beta-Antagonists↗
PubMed2002

Ratio of serum vascular endothelial growth factor to platelet count correlates with disease activity in a patient with POEMS syndrome.

Vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of POEMS (polyneuropathy, organomegaly, endocrine disorder, M-protein, and skin lesion) syndrome. Because platelets have recently been recognized as transporters of VEGF, enhanced blood coagulation activity in this syndrome may accelerate vasopermeability by releasing VEGF from platelets in vivo. Here we report a case of POEMS syndrome with anasarca showing a high ratio of serum VEGF to platelet count, indicative of massive VEGF release from aggregated platelets in vivo. Changes in the ratio clearly reflected disease activity. This observation suggests that the ratio of serum VEGF to platelet count is more precise in monitoring disease activity than serum VEGF alone, and that VEGF released in vivo is critically involved in the pathogenesis of POEMS syndrome, causing hypervasopermeability.

Journal Article↗
PubMed2002

Interferon-gamma brings additive anti-viral environment when combined with interferon-alpha in patients with chronic hepatitis C.

T-cell hyporesponsiveness may lead to chronicity of hepatitis C virus (HCV) infection. We evaluated whether interferon (IFN)-gamma injection can bring a Th1-dominant environment to patients with chronic hepatitis C. Seventeen patients with genotype 1b received natural IFN-alpha 5MU daily for the first 2 weeks and three times a week for the next 22 weeks followed by natural IFN-gamma 1 MU daily for 2 weeks. In 4 of 17 patients (23.5%), alanine aminotransferase (ALT) was normalized and 3 of these 4 patients (75.0%) cleared HCV RNA. beta2 microglobulin (BMG), neopterin and soluble (s) Fas increased with IFN-alpha and increased more with IFN-gamma. Serum interleukin (IL)-12, CD4 and CD8 remained unchanged with IFN-alpha but increased after IFN-alpha was replaced by IFN-gamma. IL-10 was not changed either with IFN-alpha or gamma. Productions of IL-2, IFN-gamma and tumor necrosis factor (TNF)-alpha by peripheral blood mononuclear cells did not change by IFN-alpha therapy, however, they were enhanced at the end of IFN-gamma therapy. Productions of IL-2 and 4 were unaffected. These results show that some immune parameters become Th1-dominant by additional IFN-gamma in patients with chronic hepatitis C. Combination of these two IFNs should be explored.

Journal Article↗
PubMed2002

High incidence of extrahepatic manifestations in an HCV hyperendemic area.

We previously investigated the incidence of extrahepatic manifestations including oral precancerous disease among the inhabitants in a hepatitis C virus (HCV) hyperendemic area in Fukuoka in Japan. The present study design was based on a prospective cohort at the other HCV hyperendemic area. One oral surgeon examined the oral lesions of 59 adult inhabitants (21 men, 38 women; mean age of 70.7 years), of a hyperendemic area of HCV infection. Furthermore, all subjects were interviewed regarding the natural history of extrahepatic manifestations. All sera were examined for antibodies to HCV (anti-HCV), serum HCV RNA, HCV genotype, antinuclear antibody (ANA), rheumatoid factor (RF) activity, and anti-SS-A and-B antibodies. Anti-HCV or HCV RNA was detected in sera from 59 (100%) or 57 (96.7%) of all subjects. Oral lichen planus (OLP), leukoplakia with leukoedema, or only leukoedema was observed in 8 (8.5%), 1 (1.7%), or 2 (3.4%) subjects, respectively. The incidence of all subjects with one or more HCV-related extrahepatic manifestation was 66.1% (39/59). The subjects with dry mouth were 25.4% (15/59). There was no relation among these autoantibodies, symptoms of dry mouth, or prevalence of HCV-associated extrahepatic manifestations. These findings demonstrate that the inhabitants with HCV infection showed various extrahepatic manifestations, and was not always limited to specific HCV areas.

Journal Article↗
PubMed2002

Short term and two-step interferon therapy for chronic hepatitis C patients with low HCV RNA levels.

Objective: Chronic hepatitis C patients with low HCV RNA levels were treated with short term therapy and for patients in whom the virus was not eliminated in this short therapy, we designed a two-step IFN therapy. Subjects: There were 31 patients with chronic hepatitis C whose HCV RNA level before IFN therapy was <1.0 Meq/ml or 100 kcopies/ml. The HCV serotypes were serotype 1 in nine patients, serotype 2 in 21 and mixed type in one. A 9--10 MU per day of natural IFN was administered daily for 2 weeks, then three times weekly for 8 weeks (the first therapy), then the therapy was ended. For patients in whom the virus was not eliminated, an additional IFN therapy was administered during the decreasing phase of HCV RNA (second therapy). The historical control group consisted of 57 patients who fulfilled the above criteria and underwent IFN therapy for 24 weeks. Complete responders were defined as patients in whom HCV RNA was not detected in their serum for at least 6 months after the end of treatment. Results: Nineteen (61%) of 31 patients who completed the first therapy showed complete response to the first therapy. Eight patients underwent the second therapy and the complete response rates were 0/4 and 2/4 (50%) in the serotype 1 and 2 groups, respectively. The overall complete response rate was 44% (4/9) in the serotype 1 group, 76% (16/21) in the serotype 2 group and 100% (1/1) in the mixed type. The complete response rate in the historical control group was 70% (40/57), showing no difference in efficacy. However, the IFN dosage was significantly lower in the patients than in the control group (P<0.001). Conclusions: In patients with low HCV RNA levels and serotype 2, short term therapy is sufficiently effective. Furthermore, 50% of the complete response was obtained by an additional second therapy. This therapy design showed high efficacy and was cost-effective in these patients.

Journal Article↗
PubMed2002

Serum HCV RNA levels during early phase of recombinant interferon alfa-2a (Roferon A) therapy for chronic hepatitis C and efficacy of short-term therapy with earlier loss of viremia.

We conducted a prospective, controlled, multicenter trial to assess if earlier changes of serum HCV RNA levels were predictable for long-term effect, and if a short-term therapy was effective in such patients. All 377 chronic hepatitis C (CH-C) patients were treated with interferon (IFN) daily 9 MU for 4 weeks. Patients positive for HCV RNA at week 1 were treated with IFN three times weekly for additional 22 weeks (group A), while those negative for HCV RNA were randomized into either regimens; three times weekly for another 22 (group B) or 12 weeks (group C). When complete responders (CR) were defined as the subjects showing sustained loss of viremia with therapy, CR rates were 17.7% (25/141) for group A, 80.0% (36/45) for group B and 61.0% (36/59) for group C, respectively. Group B showed a significantly higher CR rate than group C, indicating that a 16-week treatment period was inadequate. Patients with CR showed a rapid decrease in virus levels by day 2 after starting therapy. The CR ratio in patients with HCV RNA levels of <1.0 Kcopy/ml by day 2 was 64.6% (82/127), while the ratio without <1.0 Kcopy/ml was 12.7% (15/118). CR ratio in patients who became negative by week 2 was 65.7%, whereas only 2.9% after week 2. The results indicate that the determination of HCV RNA levels at day 2 and the qualitative assay at week 2 with IFN are useful in predicting the therapeutic effect.

Journal Article↗