Biomedical subjects
Chifumi Sato
Publications and source records attributed to Chifumi Sato.
Statin guidelines should give best statin.
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A randomized controlled trial on the long-term effects of a 1-month behavioral weight control program assisted by computer tailored advice.
OBJECTIVES: To examine the long-term effects of a new behavioral weight control program (Kenkou-tatsujin, KT program). The program consisted of twice-interactive letter communications including computer-tailored personal advice on treatment needs and behavioral modification. DESIGN: A randomized controlled trial comparing Group KM: KT program with 6-month weight and targeted behavior's self-monitoring, Group K: KT program only, Group BM: an untailored self-help booklet with 7-month self-monitoring of weight and walking, and Group B: the self-help booklet only. PARTICIPANTS: Two hundreds and five overweight Japanese females were recruited via a local newspaper. MEASUREMENTS: Weight loss (body weight, BMI, reduction quotient, etc.) and behavioral changes (daily eating, exercise and sleeping habits). FINDINGS: A significant weight loss was observed in all groups. At 1 month, Groups KM and K were superior, but at 7 months, the mean weight loss was significantly more in Group KM than the other 3 groups. At 7 months, 8 dietary habits and 4 physical activities were improved in all subjects. Habitual improvement was related to the weight loss in Groups KM and K at 1 month.
Gefitinib for refractory advanced non-small-cell lung cancer.
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Effects of introducing a critical path method to standardize treatment and nursing for early discharge from acute psychiatry unit.
This research aimed to examine whether early discharge can be performed by nurses of a ward participating in the process of critical path method supporting with offer and evaluation of standard and efficient medical treatments and nursing cares. In order to enrich the system that performs hospitable medical treatment and nursing cares standardized at the psychiatry acute term and to prevent chronic, critical path method was introduced into the acute term ward, then the investigation for nursing job satisfaction that was important to establish critical path method was conducted. By introducing critical path method, it became possible to assess the patients in standard, and the subject of business or a system became clear towards early discharge. It became possible to tie up this subject to a future improvement. Consequently, as for comparison of the patient who applied the schedule table of critical path method at the first and second term, the latter decreased the average length of hospitalization period significantly. The satisfaction of the task requirement, which was important to maintain systems, was decreased by the introduction of critical path method but the score of autonomy in satisfaction increased significantly by the improvement of usage of critical path method. From these, it was suggested that the introduction of critical path method in the acute-care unit psychiatry had possibility to aim at standardization of treatment and nursing and patients' early discharge from hospitals.
Prevalence of hepatitis E virus infection in regular hemodialysis patients.
The percentage of patients infected with blood-borne diseases, including hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, is high in patients undergoing hemodialysis regularly. Hepatitis E virus (HEV) is transmitted via the fecal-oral route, and blood-borne HEV infection has also been reported recently. On the basis of these findings, we investigated the actual status of HEV infection in regular hemodialysis patients. Out of 1077 patients undergoing hemodialysis at two key hospitals and three outpatient hemodialysis clinics, 300 were randomly selected as the subjects. Among these 300 hemodialysis patients, 19.0% were IgG-type anti-HEV antibody-positive. The percentage of HEV-infected patients increased with patient age and it was particularly high in patients 40 years of age or older. The percent IgG-type anti-HEV antibody positivity was not significantly different (P = 0.14) between anti-HCV antibody-positive patients (27.8%) and anti-HCV antibody-negative patients (17.8%). The percentage of HEV-infected patients among the hemodialysis patients was higher than that previously reported among patients with healthy kidneys. No correlation was observed between the percentage of HEV-infected patients and HCV infection incidence or a history of blood transfusion. The percent IgG-type anti-HEV antibody positivities were significantly different among the facilities. It was impossible to specify the route of infection, and the correlation between the incidence of infection and hemodialysis therapy was not clear. Because more routes of infection are possible for patients undergoing dialysis than for persons with normal kidney function, it seems necessary to analyze the significance of infection incidence, the route of infection and infection prevention measures.
Factors affecting rapid turnover of novice nurses in university hospitals.
Rapid turnover of novice nurses eventually results in a shortage of veteran nurses. This study aimed to clarify the factors affecting rapid turnover of novice nurses in a prospective manner. We carried out an investigation in 20 university hospitals whose directors of nursing service departments accepted our request to cooperate with our research program. These hospitals were selected from all of the 102 university hospitals listed in The Hospital Catalog of Japan. The subjects were 1,203 novice hospital nurses who gave their informed consent for participation in our study. The questionnaires, which dealt with burnout, assertiveness, stressful life events, reality shock, ward assignment preference, transfer preference, job satisfaction (workplace, salary, workload, and overtime), social support and coping mechanisms were completed by 923 novice nurses in June 2003. Then, their turnover was investigated in December 2003. Thirty-seven novice nurses (4.0%) quit during this period. Multiple logistic regression analysis showed that the factors affecting rapid turnover were 1) graduation from vocational nursing schools, 2) dissatisfaction with assignment to a ward contrary to their desire, and 3) no peers for support. Assignment of novice nurses to wards they choose as far as possible, avoidance of assigning novice nurses to wards alone, and establishment of a support system for nurses who graduate from vocational nursing schools seem to be important for preventing rapid turnover of novice nurses.
Enhancement of mitochondrial gene expression in the liver of primary biliary cirrhosis.
Primary biliary cirrhosis (PBC) is one of the most important autoimmune liver diseases but the etiology and pathogenesis remain unknown. In this study, we analyzed differential mRNA expression in the liver of a patient with PBC using suppression subtractive hybridization to identify overexpressed genes. Overexpression of mRNA transcripts from mitochondrial DNA was observed in the PBC liver, compared to normal liver. To explore the mechanism of increased mitochondrial transcription, we investigated the mRNA levels of nuclear DNA-encoded regulator molecules of mitochondrial gene expression in 60 liver biopsy samples from various diseases, including PBC, using competitive RT-PCR. Increased expression of mitochondrial transcriptional factor A (mtTFA) and mitochondrial nuclear respiratory factor 1 (NRF-1) mRNA was demonstrated in PBC liver compared to other liver diseases, while NRF-1 coactivator 1, PGC-1 was suppressed. Mitochondrial DNA-encoded mRNA molecules are overexpressed in the PBC liver, and this is associated with up-regulation of mitochondrial transcription factor mtTFA and its transactivator NRF-1. Further studies are needed to focus on the relevance of this perturbation of mitochondrial gene expression in the pathogenesis of PBC.
Treatment of chronic hepatitis C in blacks and non-Hispanic whites.
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Changes of HCV quasispecies during combination therapy with interferon and ribavirin.
Treatment of chronic hepatitis C virus (HCV) infection with interferon (IFN) and ribavirin improves the rate of eradication of HCV, but only about 13-14% of non-responders (NR) with HCV of genotype 1b previously treated with IFN achieve a sustained virological response (SVR). To determine whether HCV quasispecies diversity correlates with the outcome of therapy with IFN and ribavirin, we studied 13 patients undergoing combination therapy with IFN-alpha2b and ribavirin after failure of IFN monotherapy. HCV quasispecies diversity was assessed by cloning and sequencing before and during combination therapy. During therapy, quasispecies diversity diminished in NR patients, both in the hypervariable region (HVR) 1 of the envelope 2 (E2) domain and in the interferon sensitivity-determining region (ISDR) in the NS5A. Pre-treatment nucleotide quasispecies diversity was lower in SVR and end-of-therapy viral response (ETR) patients than in NR patients. Resistance to ribavirin was associated with high pre-treatment heterogeneity and the selection of quasispecies of the HCV genome. HVR quasispecies may be a predictor of efficacy of combination therapy with IFN and ribavirin.
The values and limitations of glypican-3 as a novel tumor marker for hepatocellular carcinoma from clinical and economic viewpoints.
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Hepatitis C virus nonstructural protein 5A inhibits tumor necrosis factor-alpha-mediated apoptosis in Huh7 cells.
To analyze the influence of hepatitis C virus nonstructural protein 5A (NS5A) on apoptosis, we established Huh7 cells that stably express NS5A, and induced apoptosis using tumor necrosis factor (TNF)-alpha. The viability of control Huh7 cells was reduced to 40%, compared with untreated cells, after TNF-alpha treatment, whereas that of Huh7-NS5A cells was reduced only to 80%. DNA fragmentation also decreased to <50% in Huh7-NS5A compared with control cells. Nuclear factor-kappaB activation was the same in both cell types, whereas caspase-8, -9, and -3 activity was decreased in Huh7-NS5A cells, compared with control cells, which indicates that the inhibition of caspase-8 activation is responsible for the antiapoptotic effect of the NS5A protein. The coexpression of NS5A did not inhibit apoptosis induced by caspase-8 or Fas-associating death domain protein expression. These findings suggest that the NS5A protein inhibits the apoptotic effect of TNF-alpha upstream of caspase-8 in the apoptosis cascade.
Treatment of SARS with human interferons.
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Sequence elements correlating with circulating viral load in genotype 1b hepatitis C virus infection.
The correlation between hepatitis C virus (HCV) genomic sequences and circulating HCV RNA levels was assessed to investigate the genetic elements affecting viral load. The interferon sensitivity-determining region (ISDR) sequence and the serum viral load were strongly correlated in 226 patients examined. Analysis of the entire HCV genome from six patients (three with a high and the others with a low viral load) with similar ISDR sequences identified several candidate residues associated with viral load. The amino acid (aa) sequences of these candidate residues and flanking regions in 67 additional patients revealed that only the residue at aa 962 varied significantly between the HCV patients with low and high serum loads (P=0.042). At this position, alanine was observed more frequently in the patients with a high viral load. In conclusion, our results strongly suggest that serum HCV RNA loads are inversely correlated with amino acid substitutions in the ISDR, and aa 962 was identified as a possible second determinant of serum HCV RNA load.
The interferon sensitivity determining region in the era of combination therapies and the rational use of such therapies for patients with HCV genotype 1b infection.
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Amino acid substitutions in PKR-eIF2 phosphorylation homology domain (PePHD) of hepatitis C virus E2 protein in genotype 2a/2b and 1b in Japan and interferon efficacy.
Recently, the envelope protein 2 (E2) of hepatitis C virus (HCV) was reported to interact with double stranded RNA-dependent protein kinase (PKR) through an element homologous to the phosphorylation site of PKR and its target, eukaryotic translation initiation factor (eIF) 2alpha (PKR-eIF2alpha phosphorylation homology domain: PePHD). Inhibition of the kinase activity of PKR by this interaction was postulated as a mechanism for the resistance to interferon (IFN) therapy. The aim of this study was to clarify whether the variation of PePHD amino acid sequences affects IFN efficacy in Japanese population. Amino acid sequences of PePHD (aa. 659-670 in genotype1b, aa. 663-674 in genotype 2a and 2b) were determined in randomly selected 112 patients with chronic hepatitis C (genotype 1b; 83 patients, 2a; 14 patients, 2b; 15 patients) prior to IFN monotheray. In 21 out of the 23 genotype 1b sustained responders (SR) (91%) and 55 out of the 60 non-SR (92%), PePHD sequences were identical to that of the HCV-1b consensus sequence. Only two SR showed one amino acid substitution in PePHD, and five non-SR showed amino acid substitutions in PePHD. Among 14 genotype 2a patients, only two SR had one amino acid substitution comparing to the consensus HCV-2a sequence. Likely, only one SR had an amino acid substitution in PePHD among 15 genotype 2b patients. In conclusion, our study revealed no clinical relationship between the amino acid sequence of PePHD and the outcome of IFN therapy. PePHD polymorphism was not suggested to play a role in predicting IFN efficacy.
Sialadenitis in patients with chronic hepatitis C is not directly related to hepatitis C virus.
Sjogren's syndrome has been suspected to be an extrahepatic manifestation of chronic hepatitis C virus (HCV) infection. To evaluate the association of sialadenitis with HCV infection, serum levels of salivary amylase (s-isoamylase) and antibodies to Ro (SS-A) and La (SS-B) were analyzed in 114 patients with chronic hepatitis C. Serum s-isoamylase levels were monitored before and after HCV was eradicated by interferon therapy. Immunohistochemistry and Western blotting using anti-HCV antibodies, and in situ hybridization of HCV-RNA were performed in the salivary gland. Serum s-isoamylase levels were elevated in patients with chronic hepatitis C (P<0.0001). The s-isoamylase remained high even after HCV was eradicated. The in situ hybridization did not show the presence of HCV-RNA in the salivary gland from patients with chronic hepatitis C. A protein reacting with anti-HCV-E2 antibodies was found in the cytosol fraction of normal salivary gland from HCV-negative cases. Latent sialadenitis is frequently observed in chronic hepatitis C, which is not directly related to HCV per se. The presence of a common epitope between antigenic protein in the salivary gland and the HCV-derived protein may be a possible pathogenetic mechanisms such as molecular mimicry.
Optimal IFN therapy for 40-year-old patients with severe HCV-1b infection.
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