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Biomedical subjects

J Hayashi

Publications and source records attributed to J Hayashi.

At least 73 records · Page 4Linked to original sources

Hepatitis C virus infection in institutionalized psychiatric patients: possible role of transmission by razor sharing.

The objective of this study was to determine if HCV can be transmitted from patient to patient in psychiatric institutions and to determine possible routes of infection. We did a cross-sectional survey of 196 Japanese psychiatric patients tested for HCV and HBV markers and 400 age- and sex-matched controls. Anti-HCV was detected in 10.2% and antibody to hepatitis B core antigen was detected in 44.4% of the patients, a significantly higher prevalence than found among matched controls. A multiple regression logistic analysis was used to identify risk factors that could indicate the route of infection by HCV. Duration of hospitalization, age, razor sharing, and history of surgery proved to be statistically significant independent risk factors associated with positive anti-HCV results [odds ratio (OR), 4.00; 95% confidence interval (CI), CI, 1.74-9.19; OR, 2.19; 95% CI, 1.27-1.3.77; OR, 4.90; 95% CI, 1.29-18.86; OR, 3.35; 95% CI, 0.997-11.3, respectively]. These observations suggest that razor sharing played an important role in the spread of the HCV infection in the institutionalized psychiatric patients we studied.

Adult↗

Lower hepatitis G virus infection prevalence compared to hepatitis B and C virus infection prevalences.

To more accurately determine the seroprevalence of hepatitis G virus (HGV) infection, we surveyed antibody to HGV (anti-E2) by enzyme-linked immunosorbent assay (ELISA) and HGV RNA by nested polymerase chain reaction (PCR) in 298 residents of a hepatitis C virus (HCV)-endemic area of Japan and in 225 hemodialysis patients. We then compared these findings with known HCV and hepatitis B virus (HBV) infection prevalences. Anti-E2 and HGV RNA prevalences were 32 (10.7%) and 5 (1.7%) in the residents and 24 (10.7%) and 10 (4.4%) in the hemodialysis patients, respectively. Anti-E2 and HGV RNA concurrence was found in two of the hemodialysis patients. Total HGV marker (anti-E2 and/or HGV RNA) prevalences [37 (12.4%) in residents and 32 (14.2%) in hemodialysis patients], were significantly lower than the prevalences of antibody to HCV (anti-HCV) by ELISA [59 (19.8%) and 96 (42.7%)], and antibody to hepatitis B core antigen (anti-HBc) by radioimmunoassay (RIA) [87 (29.2%) and 101 (44.9%)] (P<0.05). The anti-HCV prevalence in subjects with total HGV marker was significantly higher than in those without total HGV marker. There was no significant difference in anti-HBc prevalence between those with and without total HGV marker. The viremic rate was highest in HCV infection (HCV RNA by PCR/anti-HCV) (83.2%), with HGV infection (HGV RNA/total HGV marker) (21.7%) intermediate, and HBV infection (hepatitis B surface antigen by RIA/anti-HBc) (5.3%) lowest (P<0.05). These findings indicate that HGV infection was less endemic than HCV and HBV. HGV was eliminated naturally more frequently than HCV infection and less frequently than HBV infection.

Adolescent↗

Effectiveness of interferon treatment for patients with chronic hepatitis C virus infection and normal aminotransferase levels.

To determine the effects of interferon treatment, we studied 77 Japanese patients with hepatitis C virus (HCV) infection and normal alanine aminotransferase (ALT). Of 77 patients, 37 were given natural interferon-alpha for 24 weeks, and 40 not given interferon acted as controls. Serum samples were tested for HCV RNA and genotypes by polymerase chain reaction (PCR). HCV RNA levels were measured by competitive PCR. Of 37 treated patients, 11 (29.7%) had sustained elimination throughout a six-month follow-up, while HCV RNA was not eliminated in any untreated patients. At 24 months, the number of patients with elevated ALT was not significantly different between treated (13.5%) and untreated patients (15%). Interferon eliminates HCV RNA in patients with normal ALT without severe side effects. The natural history of HCV infection should be clarified so that the interferon treatment regimen can be tailored to the needs of each patient.

Adult↗

Seroepidemiology of TT virus infection and relationship between genotype and liver damage.

TT virus (TTV) has been identified in patients with posttransfusion hepatitis of unknown etiology and is thought to be a new hepatitis virus. We determined the extent of TTV infection in the Japanese general population and the relationship between TTV DNA genotype and liver damage. In 1998, we tested 847 serum samples for TTV. TTV DNA was assayed by a nested polymerase chain reaction and classified into three different genotypes and eight subtypes. TTV DNA was detected in 25.3% and 32.4% of the inhabitants of the two areas studied, respectively. The genotype distribution was similar in both areas. G1, G2, and G3 were 60%, 20%, and 5%, respectively. Of the 20 subjects with TTV DNA alone and elevated serum ALT levels, 18 were G1, one was G2, and one was G3. TTV infection is endemic in the Japanese general population studied. The main TTV genotype, G1, may be related to the ensuing liver damage.

Adolescent↗

Liver damage in hemodialysis patients with hepatitis C virus viremia: a prospective 10-year study.

Hepatitis C virus (HCV) infection is a major problem associated with hemodialysis. The extent of liver damage in hemodialysis patients with chronic HCV infection has not been thoroughly documented. The aim of this study was to evaluate liver damage of hemodialysis patients infected with HCV. A total of 233 hemodialysis patients were categorized into two groups at entry: group X, 80 positive for serum HCV RNA, and group Y, 153 negative for serum HCV RNA. All were tested for serum alanine aminotransferase (ALT) serially from 1989 to 1998, and serum hyaluronic acid (HA), serum type-IV collagen (IV-C), platelet counts, and ultrasonographic examination of the liver was done in 1998. In group X, 61.3% had continuously abnormal ALT levels for over six months followed by normal ALT levels. Of the group X patients, 11.3% had abnormal ALT levels in 1998, and in three, hepatocellular carcinoma occurred. Mean HA and IV-C levels in group X (648.8 and 188.7 ng/ml, respectively) were significantly higher than in group Y (213.1 and 165.5 ng/ml, respectively) (P < 0.05). Ultrasonographic findings significantly correlated with serum HA level and platelet counts and showed significantly more abnormalities in group X than in group Y (P < 0.05). From these findings, a combined examination with ultrasonography and serum fibrogenesis markers is useful for detection of liver damage in hemodialysis patients with HCV viremia.

Adult↗

Hepatitis C virus core protein activates the MAPK/ERK cascade synergistically with tumor promoter TPA, but not with epidermal growth factor or transforming growth factor alpha.

Persistent hepatitis C virus (HCV) infection is associated with the development of human hepatocellular carcinoma (HCC), although the mechanism of HCV-related hepatocarcinogenesis remains unclear. Recently, however, the close relationships between the development of HCC and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) cascade have been described. In the present study, we investigated the effects of HCV core protein on this MAPK/ERK cascade. HCV core protein significantly activated the MAPK/ERK cascade, including Elk1. We also examined whether HCV core protein acted synergistically along with hepatocyte mitogen-mediated MAPK/ERK activation. Interestingly, Elk-1 activities were further enhanced by the tumor promoter, 12-O-tetradecanoyl phorbol 13-acetate (TPA), but not by hepatocyte mitogens (epidermal growth factor [EGF] and transforming growth factor alpha [TGF-alpha]) in NIH3T3 cells and HepG2 cells expressing HCV core protein. Moreover, the MAPK/ERK activation by HCV core protein was blocked in the presence of the specific MEK1 inhibitor, PD98059. These results indicate that ERK activation by HCV core protein may be independent of hepatocyte mitogen-mediated signaling but synergistic with TPA, and HCV core protein may function at MEK1 or farther upstream of that component.

3T3 Cells↗

Cardiac strangulation in a neonatal case: a rare complication of permanent epicardial pacemaker leads.

A newborn female underwent pacemaker implantation with epicardial pacing leads for the treatment of bradycardia caused by congenital atrioventricular block. At 10 months after pacemaker implantation, she was admitted with congestive heart failure. The epicardial leads were seen to encircle the heart, and myocardial ischemia was suggested. During cardiac catheterization she collapsed: emergency operation was performed, but she died on postoperative day 6.

Bradycardia↗

Mitochondrial dysfunction increases expression of endothelin-1 and induces apoptosis through caspase-3 activation in rat cardiomyocytes in vitro.

We have reported that the expression of endothelin-1 (ET-1) increases in the failing heart. With the progress of heart failure, it has been reported that energy metabolism switches from mitochondrial b-oxidation to glycolysis. Furthermore, it has been reported that apoptosis is induced in the failing heart. However, it is not known how the gene expression of preproendothelin-1 and cellular apoptosis are affected by the mitochondrial dysfunction. Therefore, in order to elucidate this problem, we developed an in vitro model of mitochondrial dysfunction using rotenone, a mitochondrial respiratory chain complex I inhibitor, and studied preproendothelin-1 gene expression and apoptosis. Rotenone greatly increased the gene expression of pre-proendothelin-1 in cardiomyocytes. This result suggests that the gene expression of preproendothelin-1 is induced by the mitochondrial dysfunction. Furthermore, treatment of cardiomyocytes with rotenone induced an elevation of caspase-3 activity, and caused a marked increase in DNA laddering, an indication of apoptosis. In conclusion, it is suggested that mitochondrial impairment in primary cultured cardiomyocytes induced by rotenone in vitro, mimics some of the pathophysiological features of heart failure in vivo, and that ET-1 may have a role in myocardial dysfunction with impairment of mitochondria in the failing heart.

Animals↗

Identification of a two-component signal transduction system involved in fimbriation of Porphyromonas gingivalis.

Porphyromonas gingivalis, a periodontopathogen, is an oral anaerobic gram-negative bacterium with numerous fimbriae on the cell surface. Fimbriae have been considered to be an important virulence factor in this organism. We analyzed the genomic DNA of transposon-induced, fimbria-deficient mutants derived from ATCC 33277 and found that seven independent mutants had transposon insertions within the same restriction fragment. Cloning and sequencing of the disrupted region from one of the mutants revealed two adjacent open reading frames (ORFs) which seemed to encode a two-component signal transduction system. We also found that six of the mutants had insertions in a gene, fimS, a homologue of the genes encoding sensor kinase, and that the insertion in the remaining one disrupted the gene immediately downstream, fimR, a homologue of the response regulator genes in other bacteria. These findings suggest that this two-component regulatory system is involved in fimbriation of P. gingivalis.

Amino Acid Sequence↗

Increased frequency of interferon-gamma-producing peripheral blood CD4+ T cells in chronic hepatitis C virus infection.

OBJECTIVES: To determine the profile of cytokine secretion by CD4+ T helper (Th) cells in chronic hepatitis C virus (HCV) infection, we used flow cytometry to determine the percentage of interferon (IFN)-gamma and interleukin (IL)-4 producing cells from CD4+ T lymphocytes in peripheral blood obtained from patients chronically infected with HCV. METHODS: Peripheral blood mononuclear cells isolated from 89 HCV infected subjects (22 asymptomatic carriers, 56 patients with chronic hepatitis, and 11 patients with liver cirrhosis) and 24 healthy controls were stained with surface CD4 and intracellular IFN-gamma and IL-4. Serum soluble IL-2 receptor (sIL-2R) levels were analyzed by ELISA. RESULTS: The frequency of IFN-gamma producing CD4+ cells in asymptomatic HCV carriers, patients with chronic hepatitis, and patients with liver cirrhosis were significantly higher than those of healthy controls (p<0.01, respectively). In contrast, the percentages of IL-4-producing CD4+ cells were very low, and there were no significant correlations with disease progression. A significant elevation in serum sIL-2R levels was found in chronic HCV infection compared to healthy controls, and serum sIL-2R levels significantly correlated with the frequency of IFN-gamma-producing cells. CONCLUSIONS: In HCV infected subjects, both serum sIL-2R and IFN-gamma are increased in chronic HCV infection no matter the stage of disease, meaning they are no different in asymptomatic carriers, patients with chronic hepatitis, and patients with liver cirrhosis, and that Th1 cytokine or Th1 cells may participate in the pathogenesis of liver damage in chronic HCV infection.

Aged↗

Maintenance hemodialysis decreases serum hepatitis C virus (HCV) RNA levels in hemodialysis patients with chronic HCV infection.

OBJECTIVE: Hepatitis C virus (HCV) infection is a major complication among hemodialysis patients the world over. To determine the natural course of HCV viremic levels in patients on maintenance hemodialysis, we prospectively quantified the HCV RNA levels in serial blood samples from hemodialysis patients and compared them with those in nonuremic subjects. METHODS: The population studied included 98 hemodialysis patients and 228 nonuremic subjects with chronic HCV infection. HCV RNA was detected by polymerase chain reaction (PCR) and the levels were determined by branched DNA probe assay. HCV RNA genotypes were determined by PCR using type-specific primers. RESULTS: HCV RNA levels were significantly lower in hemodialysis patients (median, 0.4x10(6) genome equivalent [Meq]/ml) than in nonuremic subjects (median, 3.0 Meq/ml) (p<0.05). HCV of genotype 1b was prevalent in the hemodialysis patients (81.6%) and nonuremic subjects (88.6%). HCV RNA levels in 20 hemodialysis patients with genotype 1b were significantly reduced after each hemodialysis procedure (p<0.05). The 3-yr prospective observation from 1995 to 1998 showed a significant decrease of HCV RNA levels in 47 hemodialysis patients with genotype 1b (median, 1.9-0.9 Meq/ml, p<0.05), whereas levels in 155 nonuremic subjects with genotype 1b did not decrease (median, 2.6-3.0 Meq/ml). There were no patients or nonuremic subjects with undetectable HCV RNA by a PCR assay during the observation period. CONCLUSIONS: These observations suggest that maintenance hemodialysis decreases the HCV RNA levels in hemodialysis patients with chronic HCV infection, but does not produce clearance of the viremia.

Adult↗

[The efficacy of influenza vaccine among geriatric inpatients].

To investigate the efficacy of influenza vaccine in the elderly, hemagglutination inhibition (HI) antibody titer for the three types of influenza viruses were measured and the influenza infection rate was determined serologically in geriatric inpatients. Influenza vaccination was done for inpatients. For patients who had influenza vaccination in the year prior to the study, influenza vaccine was administered once or twice, and the number of injections were determined randomly. Influenza vaccine was injected twice to those had not received influenza vaccine in the previous year. Serum samples were collected from 166 vaccinated and 104 unvaccinated patients before and after 1996/1997 influenza season. In the vaccinees who had been vaccinated the previous year, 56 patients were injected once and 58 patient were injected twice. Fifty-two patients had not been vaccinated the previous year. Serologically diagnosed influenza infection rate in the 104 unvaccinated patients was 16.3% for influenza A/H3N2 and 8.7% for influenza B. The infection rate was 3.0% for influenza A/H3N2 and 0.6% for influenza B in the 166 vaccinated patients. The infection rates were significantly lower in the vaccinees than in the unvaccinated patients (p < 0.001 with A/H3N2 and p < 0.01 with B). There was no significant difference in the infection rate among the three vaccinated groups. These results suggest that the influenza vaccination had significant protective efficacy for influenza infection in the elderly. Prior vaccination did not diminish the efficacy of the influenza vaccine. The efficacy of a single influenza vaccine injection was equivalent to that of two injection.

Aged↗

[The clinical feature of febrile episodes].

Institutionalized elderly patients are at risk of nosocomial infection because of their compromised status by aging. To clarify the relationship between fever and disease in elderly patients, we analyzed 1,105 febrile episodes, the etiology of which were already diagnosed, of 443 patients (136 men, 307 women). All patients who were 65 years of age or older and who had been admitted to the hospital for more than 7 days had fevers above 37.5 degrees C recorded. The etiologies of the 1,105 febrille episodes were respiratory tract infection in 381 (34.5%), urinary tract infection in 263 (23.8%), other diseases in 164 (14.8%) and in 297 (26.9%) unknown. The episodes were categorized into two groups by the degree of initial fever: group A, 559 episodes (50.6%) of 37.5-38.0 degrees C and group B, 546 episodes (49.4%) of above 38.0 degrees C. Of the episodes, 41.0% were one-day fevers, 21.4% two-day fevers, and 14.0% three-day fevers. The frequency of two-or-more-day fevers was significantly higher in group B (69.0%) than in group A (49.2%) (p < 0.001). In group B, respiratory tract infection (44.3%) was more frequent than urinary tract infection (16.1%) (p < 0.001). Of the respiratory tract infections, 63.5% were in group B and, in contrast, 66.5% of the urinary tract infections were in group A. The white blood cell count and C-reacting protein levels were significantly higher in group B than in group A (p < 0.001). The degree of initial fever is an important predictive marker of severity of disease in elderly patients.

Aged↗

[Amantadine usage for influenza A during an influenza outbreak in a nursing home].

An outbreak of an influenza like illness was found in a nursing home in Fukuoka in January, 1999. Results of hemagglutinin inhibition tests with paired sera of patients and rapid diagnosis kit for influenza A indicated that an influenza A (H3N2) outbreak had occurred. A total of 15 patients with influenza like illness from one residential area of the nursing home were administered amantadine, 100 mg per day for five days. Clinical records of 264 residents were surveyed retrospectively from the tenth to the thirty-first of January, 1999. Influenza like illness was found in 112 residents (42.4%). The incidence of influenza like illness differed by residential area, ranging from 27.6% to 54.0%. The mean duration of fever was 3.6 days among patients administered amantadine. The mean duration was 4.4 days for patients not administered amantadine. The incidence of influenza like illness decreased rapidly after amantadine administration in the residential area where amantadine administration was done. These results suggest that amantadine is effective in mitigating influenza symptoms in the elderly. Amantadine may be useful for diminishing the influence of influenza A outbreaks in nursing homes.

Aged↗

Characterization of the relA gene of Porphyromonas gingivalis.

Based upon the nucleotide sequence of the relA gene from Escherichia coli, a gene fragment corresponding to the homologous gene from the pathogenic oral bacterium Porphyromonas gingivalis 381 was isolated by PCR and utilized to construct a relA mutant. The mutant, KS7, was defective in ribosome-mediated ppGpp formation and also in the stringent response.

Amino Acid Sequence↗

Hepatitis C virus core protein interacts with 14-3-3 protein and activates the kinase Raf-1.

Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver dysfunction in humans and is epidemiologically closely associated with the development of human hepatocellular carcinoma. Among HCV components, core protein has been reported to be implicated in cell growth regulation both in vitro and in vivo, although mechanisms explaining those effects are still unclear. In the present study, we identified that members of the 14-3-3 protein family associate with HCV core protein. 14-3-3 protein bound to HCV core protein in a phosphoserine-dependent manner. Introduction of HCV core protein caused a substantial increase in Raf-1 kinase activity in HepG2 cells and in a yeast genetic assay. Furthermore, the HCV core-14-3-3 interaction was essential for Raf-1 kinase activation by HCV core protein. These results suggest that HCV core protein may represent a novel type of Raf-1 kinase-activating protein through its interaction with 14-3-3 protein and may contribute to hepatocyte growth regulation.

14-3-3 Proteins↗

Influenza in three patients with human immunodeficiency virus infection.

Three Japanese outpatients with human immunodeficiency virus (HIV) infection on anti-retroviral therapy showed evidence of influenza in January 1999. CD4+ T cell counts of these patients prior to the diagnosis of influenza were 72, 248, and 152/mm3, and HIV RNA levels were 19,953, 1,259, and 1,585 copies/ml, respectively. Fever continued 4 to 5 days with no severe complications. One patient showed post-influenzal bronchitis which was effectively treated by antibiotics. None of these patients showed increased serum HIV RNA levels during and after influenza, however, in one patient, a transient reduction of CD4+ and CD8+ cells was seen during the active phase of influenza. Although symptoms of influenza in HIV carriers are generally mild and similar to those in healthy adults, careful follow-up is needed as symptoms of influenza in some HIV-infected patients can be prolonged and serious.

AIDS-Related Opportunistic Infections↗

p53 null mutations undetected by immunohistochemical staining predict a poor outcome with early-stage non-small cell lung carcinomas.

The importance of p53 mutations in the pathogenesis of human lung carcinoma is well established, but it is still controversial whether the presence of p53 mutations or overexpression of p53 protein adversely affects an individual patient's chances of survival. The controversy may be partially due to the methodological differences in examination for p53 alterations: gene analysis or immunohistochemical staining. Furthermore, recent studies have suggested that different types of mutations of the p53 tumor suppressor gene confer different biological properties. To clarify the relationship between immunohistochemical staining and prognosis, we investigated mutations using single-strand conformation polymorphism followed by sequencing for exons 4-8 and 10 in 144 surgically treated non-small cell lung carcinoma patients with intensive clinical follow-up. Of 144 cases, 107 adenocarcinomas were examined for immunohistochemical staining with RSP53 antibody. p53 gene mutations were observed in 65 tumors (45%), including 44 missense and 21 null mutations, the latter comprising 7 nonsense mutations, 8 deletions, 2 insertions, and 4 splicing junction mutations. Presence of p53 mutations was an independent prognostic factor with a statistical trend (P = 0.14) in stage I patients but not in all cases. When examined by mutational pattern, null mutation was a significant indicator of poor outcome by multivariate analysis (P = 0.03) in stage I patients, whereas cases with missense mutations and without mutations did not differ (P = 0.76). Forty (37%) tumors demonstrated overexpression of the p53 protein but without any survival difference. Most tumors (76%) with missense mutations were immunopositive, but those with null mutations with one exception (93%) were not, and the concordance between the mutations and immunohistochemical staining was rather low at 65%. These data suggest that the type of p53 mutation is important for prediction of outcome in early-stage non-small cell lung carcinoma patients, whereas immunohistochemical staining for abnormal p53 gene products is nonpredictive. Furthermore, null mutations causing loss of function of the gene product may play more important roles than missense mutations in tumor progression.

Adenocarcinoma↗