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Biomedical subjects

Jun Hayashi

Publications and source records attributed to Jun Hayashi.

At least 55 records · Page 3Linked to original sources

Increased frequency of CD27- (naive) B cells and their phenotypic alteration in HIV type 1-infected patients.

To investigate HIV-1-related B cell disorders, the quantity of peripheral CD27 negative (CD27-) B cells, their CD38, CD95, and bcl-2 intensities, and their apoptosis susceptibility were examined by flow cytometry analysis in 16 drug-naive patients, 27 HAART-treated patients, and 20 uninfected controls. CD27- B cells have been recognized as naive B cells. The mean percentage of CD27- B cells was significantly higher in drugnaive patients (88.1%) and in HAART-treated patients (83.9%) than in controls (68.6%) (p < 0.01). The intensities of CD38 and CD95 on CD27- B cells were significantly higher in drug-naive patients than in controls (p < 0.01). The intensity of CD95 on CD27- B cells in HAART-treated patients was lower than that of drug-naive patients, but significantly higher than that of controls (p < 0.01). The intensity of bcl-2 on CD27- B cells in drug-naive patients was lower than that of controls. In drug-naive patients, CD27-B cells with high CD38 expression represented low bcl-2 expression. The CD27- B cells of drug-naive patients showed an increased susceptibility to apoptosis, characterized by diminished cell size and a high frequency of annexin-V binding, compared with controls and HAART-treated patients. These findings suggested that HIV-1 infection affects peripheral CD27- (naive) B cells as well as CD27+ (memory) B cells and that CD27- B cells might be activated and rendered highly susceptible to apoptosis by HIV-1 infection. Some phenotypic alterations in CD27- B cells may continue after the reduction of HIV-1 loads by effective antiviral therapy.

ADP-ribosyl Cyclase↗

Selective CD27+ (memory) B cell reduction and characteristic B cell alteration in drug-naive and HAART-treated HIV type 1-infected patients.

To investigate HIV-1-related B cell disorders, the quantity of CD27 positive (CD27+) B cells and their CD38, CD95, and bcl-2 intensities were examined by flow cytometry analysis in 16 drug-naive patients, 27 highly active antiretroviral therapy (HAART)-treated patients, and 20 uninfected controls. CD27+ B cells have been recognized as memory B cells. The mean percentage of CD27+ B cells was significantly lower in drug-naive patients (11.9%) and in HAART-treated patients (16.1%) than in controls (31.4%) (p < 0.01). The intensities of CD38 and CD95 on CD27+ B cells were higher in drug-naive patients than in controls (p < 0.01 in CD95). The intensity of CD95 on CD27+ B cells in HAART-treated patients was lower than that of drug-naive patients, but significantly higher than that of controls (p < 0.01). The intensity of bcl-2 on CD27+ B cells was equivalent among the three groups. These findings suggest that disturbance of peripheral B cell composition, exemplified by CD27+ B cell reduction, exists in both drug-naive and HAART-treated HIV-1-infected patients. In addition, the augmented apoptotic state of CD27+ B cells found in HAART-treated patients with undetectable viral loads, indicated by CD95 elevation, suggests that some HIV-1-related B cell disorders last for years after effective antiviral therapy.

ADP-ribosyl Cyclase↗

Double point mutation in the core promoter region of hepatitis B virus (HBV) genotype C may be related to liver deterioration in patients with chronic HBV infection.

BACKGROUND AND AIM: Hepatitis B virus (HBV) genotype C has a more severe pathogenesis than genotype B in Japan. We retrospectively investigated the relationship between HBV genotype and the core promoter (CP) (nt 1762 and 1764) and precore (PreC) (nt 1896) mutations of the HBV genome. METHODS: A total of 129 Japanese patients (42 genotype B and 87 genotype C) with chronic HBV infection, living in two different geographical areas in Japan, were evaluated (mean follow-up period 10.1 +/- 3.8 years). In 2000, CP and PreC HBV mutations were analyzed by direct sequencing from sera. Hepatitis B e antigen (HBeAg), HBV DNA and serial alanine aminotransferase (ALT) changes were followed and determined using serological methods. RESULTS: Genotype C patients had significantly higher rates of HBeAg (40.2%vs 2.4%), HBV DNA positivity (75.9%vs 7.1%) and ALT abnormality (71.3%vs 11.9%) than genotype B patients (all P < 0.05). Among genotype B patients, CP wild type (92.9%) was predominant and PreC mutation (88.1%) was predominant. However, among genotype C patients, CP mutation (75.9%) was predominant and PreC mutation (66.7%) was predominant. The CP mutation was found significantly more in genotype C than in genotype B (P < 0.05). Of the 67 patients with ALT abnormality, five (7.5%) genotype B and 62 (92.5%) genotype C patients (31 HBeAg positive and 31 negative) were found. Among the 31 genotype C patients who were HBeAg positive, the combination of CP mutation and PreC wild (54.8%) was predominant, while among the remaining 31 genotype C patients who were HBeAg negative, the combination of CP mutation and PreC mutant (71.0%) was predominant. CONCLUSION: Genotype C might be one of the worse prognostic markers in patients with chronic HBV infection, possibly because of mutation in the CP region.

Adult↗

Factors contributing to ribavirin-induced anemia.

BACKGROUND AND AIM: Interferon and ribavirin combination therapy for chronic hepatitis C produces hemolytic anemia. This study was conducted to identify the factors contributing to ribavirin-induced anemia. METHODS: Eighty-eight patients with chronic hepatitis C who received interferon-alpha-2b at a dose of 6 MU administered intramuscularly for 24 weeks in combination with ribavirin administered orally at a dose of 600 mg or 800 mg participated in the study. A hemoglobin concentration of <10 g/dL was defined as ribavirin-induced anemia. RESULTS: Ribavirin-induced anemia occurred in 18 (20.5%) patients during treatment. A 2 g/dL decrease in hemoglobin concentrations in patients with anemia was observed at week 2 after the start of treatment. The hemoglobin concentration in patients with > or =2 g/dL decrease at week 2 was observed to be significantly lower even after week 2 than in patients with <2 g/dL decrease (P < 0.01). A significant relationship was observed between the rate of reduction of hemoglobin concentrations at week 2 and the severity of anemia (P < 0.01). Such factors as sex (female), age (> or =60 years old), and the ribavirin dose by body weight (12 mg/kg or more) were significant by univariate analysis. CONCLUSIONS: Careful administration is necessary in patients > or =60 years old, in female patients, and in patients receiving a ribavirin dose of 12 mg/kg or more. Patients who experience a fall in hemoglobin concentrations of 2 g/dL or more at week 2 after the start of treatment should be monitored with particular care.

Adult↗

A decrease in mother-to-child transmission of human T lymphotropic virus type I (HTLV-I) in Okinawa, Japan.

To investigate the chronologic change of mother-to-child transmission of human T lymphotropic virus type I (HTLV-I) in Okinawa, Japan, the presence of antibody to HTLV-I was tested in 4,187 healthy residents between, 4,528 nursery school children, and 3,837 pregnant women between 1968 and 2000. The chronologic change of the feeding method and the length of the breast-feeding period among 1,117 healthy mothers from 1937 to 1995 were also obtained by interview. Age-adjusted prevalence of HTLV-I among healthy residents decreased from 9.1% in 1968-1970 to 7.8% in 1981-1984 and to 6.3% in 1996-1998. The crude prevalence of antibody to HTLV-I among healthy residents less than 20 years old decreased significantly from 4.6% in 1968-1970 to 0.1% in 1996-1998 (P < 0.0001). The prevalence of antibody to HTLV-I among nursery school children decreased significantly over the study period, from a high of 1.8% in 1984 to a low of 0.2% in 1998 (P = 0.03). The prevalence among pregnant women decreased significantly from 5.6% in 1989-1992 to 3.7% in 1997-2000 (P = 0.0275). Prior to 1967, all healthy mothers breast-fed their children. After 1968, the use of bottled and mixed milk (breast milk and bottled milk) increased, with bottled milk becoming predominant after 1990 (89%). The percentage of healthy mothers breast-feeding for more than one year significantly decreased from 68.3% in 1937-1947 to 0.4% in 1990-1995 (P < 0.0001). Infection with HTLV-I in Okinawa has decreased mainly due to a reduction in the number of mothers breast-feeding and a shortening of the breast-feeding period. However, because the mother-to-child transmission rate among non-breast-feeders decreased from 12.8% in 1986-1991 to 3.2% in 1995-1999, there may be other factors involved in the decrease in mother-to-child transmission.

Adolescent↗

Relationship of genotype rather than race to hepatitis B virus pathogenicity: a study of Japanese and Solomon Islanders.

The aim of this study was to determine the predominant hepatitis B virus (HBV) genotype in the Solomon Islands and determine if there is any racial correlation between genotype and hepatitis B e antigen (HBeAg) production in Japanese and Melanesian individuals. A total of 403 serum samples from 206 Melanesian HBV carriers in the Solomon Islands and 197 Japanese carriers from Fukuoka (n = 106) and Okinawa (n = 91) living in Japan in 2001 were tested. The HBV genotypes of 206 Melanesian subjects were 114 with genotype C (55.3%) and 92 with genotype D (44.7%). The HBV genotypes of 197 Japanese subjects were 74 with genotype B (37.6%) and 123 with genotype C (62.4%). The total HBeAg prevalence of subjects in Fukuoka (36.8%) was significantly higher than that of subjects in Okinawa (14.3%) (P < 0.0001) and subjects in the Solomon Islands (35.0%; P = 0.0014, by the Mantel-Haenszel test). The genotype C prevalences were significantly different, ranging from 24.2% in Okinawa, to 54.4% in the Solomon Islands, to 95.3% in Fukuoka (all P < 0.0001, by chi-square test). The prevalence of HBeAg positivity was significantly higher in Melanesian genotype C subjects (42.0%) than Melanesian genotype D subjects (26.6%) (P = 0.0310). Similarly, the prevalence of HBeAg positivity was significantly higher in Japanese genotype C subjects (36.6%) than Japanese genotype B subjects (9.5%) (P < 0.0001). These findings indicate that that HBV was of genotypes C and D in the Solomon Islands, and that the pathogenesis of HBV-infected patients is related to HBV genotype rather than race.

Adolescent↗

A delayed type hypersensitivity (DTH) skin reaction to hepatitis B surface antigen (HBsAg) and intradermal hepatitis B vaccination.

The significance of a delayed type hypersensitivity skin reaction to hepatitis B surface antigen (HBsAg) (HBs-DTH) in type B viral hepatitis (VHB) and in intradermal hepatitis B (HB) vaccination is reviewed. HBs-DTH could be developed by the intradermal injection of HB vaccine in anti-HBs positive people and also in persons immunized with HB vaccine. Thus, HBs-DTH could serve as a useful marker for the acquisition of an active Th1 type immunoreactivity to HBsAg. HBs-DTH was absent in patients with chronic VHB. In contrast, HBs-DTH developed early in the convalescent phase of the acute VHB, whereas the production of anti-HBs was significantly delayed, thus suggesting that HBs-DTH may be involved in the recovery mechanisms of acute VHB. Intradermal HB vaccination is useful not only in lowering the cost, but also in the rapid development of anti-HBs, reversing non-responsiveness, improving postexposure prophylaxis and in immunizing immunosuppressed people. A similar vaccination strategy should prove to be useful in prevention and control of not only other infectious diseases but also malignant neoplasms.

Hepatitis B Surface Antigens↗

Hepatoprotective and antihyperliposis activities of in vitro cultured Anoectochilus formosanus.

The pharmacological effects of an aqueous extract of the whole plants of in vitro cultured Anoectochilus formosanus were investigated experimentally for hepatoprotective and antihyperliposis activities. The extract showed significant antihepatotoxic activity against carbon tetrachloride induced cytotoxicity in primary cultured rat hepatocytes. In an assay for antihyperliposis using aurothioglucose-induced obese mice, the extract suppressed significantly the increase in the weights of body and liver, ameliorated triglyceride levels in the liver and serum, and also significantly reduced the deposition of adipose tissue.

Adipose Tissue↗

A patient in whom only hepatitis B virus (HBV) was thought to have been contracted, by kissing, from a same-sex partner coinfected with HBV and human immunodeficiency virus-1.

A 31-year-old homosexual man was admitted to our hospital in August 2001 with liver dysfunction. His diagnosis was acute hepatitis B. He had had a steady partner coinfected with hepatitis B virus (HBV) and human immunodeficiency virus-1 (HIV) from August 2000 to July 2001. Because he knew that the partner was infected with HIV, the sexual relationship had included only deep kissing, with no oral-genital or anal-genital sex. The serum HBV DNA level of the partner was relatively high compared with the serum HIV RNA level. Direct sequencing of the full HBV DNA genome from serum showed that the entire base sequences of the viruses from both patients were of genotype A and identical. HBV infectivity was shown to be stronger than that of HIV in our patient, in whom only HBV was transmitted from a partner coinfected with HBV and HIV. This case highlights the importance of HBV as a sexually transmitted disease.

Acute Disease↗

A prospective comparison of the effect of interferon-alpha and interferon-beta treatment in patients with chronic hepatitis C on the incidence of hepatocellular carcinoma development.

To investigate differences in the effect of interferon (IFN) -alpha and IFN-beta treatment for hepatitis C on hepatocellular carcinoma (HCC) development, we prospectively followed 351 consecutive patients (median age, 56.6 years; mean follow-up, 5.7 +/- 2.6 years) with chronic hepatitis C virus (HCV) viremia. Of 260 IFN-alpha and 91 IFN-beta treated patients, 17 (6.5%) and 4 (4.4%), respectively, developed HCC. Virological response (VR) was defined as persistent HCV RNA disappearance from serum, and biochemical response (BR) as persistent alanine aminotransferase (ALT) normalization after treatment. No significant between-group differences in HCC development were found between those with and without VR. Although the HCC development rate in patients without BR was significantly higher than that in patients with BR in the IFN-alpha group (11.4% and 0.8%; P << 0.05), no significant difference was found in the IFN-beta group (6.3% and 2.3%). Similar rates of HCC development were found in patients with chronic HCV viremia treated with either IFN-alpha or IFN-beta.

Adult↗

Association of Chlamydia pneumoniae antibody with the cholesterol-lowering effect of statins.

To investigate the association between Chlamydia pneumoniae (C. pneumoniae) infection and atherosclerosis, we compared the effect of lipid-lowering drugs on carotid intima-media thickness (IMT) between patients who were positive and negative for C. pneumoniae antibodies. A total of 165 asymptomatic hypercholesterolemic patients were randomized to probucol (500 mg per day, n = 82) or pravastatin (10 mg per day, n = 83) and followed for 2 years. The 2-year change of IMT in the common carotid artery was the primary endpoint, while mean IMT change and major cardiovascular events were secondary endpoints. C. pneumoniae antibodies (IgA and IgG) were measured by enzyme-linked immunosorbent assay. The 50 patients without C. pneumoniae antibodies showed significant reduction of IMT progression (-19%), while no significant change of IMT was noted in the 115 antibody-positive patients (-6%). Significant inverse associations were found between the reduction of IMT progression and the C. pneumoniae IgA- and IgG-antibody index (P < 0.01 and 0.01, respectively). No significant differences in the reduction of serum total-cholesterol and LDL-cholesterol were found between antibody-positive and -negative patients. There was no significant difference of efficacy between probucol and pravastatin. These observations suggest that C. pneumoniae infection reduces the effect of lipid-lowering therapy on carotid atherosclerosis and that this organism may play a role in the progression of atherosclerosis.

Adult↗

Carotid artery lesions and atherosclerotic risk factors in Japanese hemodialysis patients.

To determine the prevalence and severity of carotid artery lesions and which risk factors might be responsible for atherosclerosis in end-stage renal disease (ESRD) patients, we tested for carotid atherosclerosis (CA) by ultrasonography and compared the CA prevalence with well-known or suspected atherosclerotic risk factors in 226 hemodialysis (HD) patients and 2410 healthy residents of Japan. The CA prevalence was higher in the HD patients than in the healthy residents. Univariate analysis showed that HD patients with CA had a higher frequency of diabetes mellitus and left ventricular hypertrophy, and were significantly older, had significantly higher systolic blood pressure and pulse pressure, and lower albumin levels than those without. Multivariate analysis showed that age, pulse pressure, phosphorus, duration of HD, and diabetes mellitus were independent, significant predictors for CA in the HD patients. Neither Chlamydia pneumoniae seropositivity nor elevated homocysteine level was independently, significantly associated with CA. Our results suggest that HD patients had more advanced CA than the healthy residents. CA in the HD patients may be associated not only with several conventional risk factors but also with non-conventional risk factors such as phosphorus and the HD procedure itself.

Adult↗

Pilot study of prolonged interferon-alpha retreatment in chronic hepatitis C patients with genotype 1b.

OBJECTIVES: To investigate the efficacy of prolonged IFN retreatment for 3 years in chronic hepatitis C patients with high viral load and IFN treatment-resistant genotype 1b. PATIENTS AND METHODS: The study was conducted in 12 patients, not HCV RNA-negative after completion of the initial treatment. Retreatment consisted of administration of 6 million international units (MIU) of natural interferon-alpha, two or three times a week for 3 years. RESULTS: One patient was withdrawn for personal reasons. All other 11 patients completed treatment without any serious adverse reactions and were followed for 3 years. Of the patients, 4 (36%) showed a sustained virological response, 5 (45%) showed a biochemical response, and 2 (18%) relapsed after retreatment. All patients with a sustained response had a transient response to initial therapy. Patients showing a sustained response tested negative for HCV RNA within the first 6 months of retreatment. CONCLUSIONS: After prolonged IFN retreatment, a significant number of patients showed a sustained response for the first time and long-term improvement in ALT level.

Journal Article↗

[Evaluation of an immunochromatography test kit for rapid diagnosis of influenza].

We assessed the sensitivity and specificity of the Capilia Flu AB rapid diagnosis kit for influenza that utilizes the immunochromatography method. Tested were 114 influenza like illness patients in the 2001/2002 influenza season. We used Capilia Flu AB and Infu A . B Quick, a rapid diagnosis kit based on enzyme immunoassay. As laboratory confirmation tests, influenza virus isolation and polymerase chain reaction (PCR) were done. Those patients with positive results from virus isolation or PCR were regarded as influenza patients. The sensitivities of nasal swab, pharyngeal swab, and nasal wash specimens were 82.8%, 80.0%, and 75.0%, respectively. The specificities of nasal swab, pharyngeal swab, and nasal wash specimens were 95.3%, 93.9%, and 100%, respectively. A total of 20 patients displayed different results in comparison of their nasal and pharyngeal swabs: 15 patients were positive with the nasal swab but negative with the pharyngeal swab and 5 patients were negative with the nasal swab but positive with the pharyngeal swab. Nasal swab would seem to be preferable in terms of sensitivity. The sensitivity and specificity of Capilia Flu AB were a little higher than those of Influ A . B Quick, but with no significant difference. The one-step operation of Capilia Flu AB is easier than the four steps required by Influ A . B Quick, but the time required to make a diagnosis is the same. No significant age related difference in the effectiveness of the kits was found. The Capilia Flu AB rapid diagnosis kit is useful in clinical practice because it has good sensitivity (about 80%) and specificity (about 90%), and it is easy to use.

Adolescent↗

PC cell-derived growth factor (granulin precursor) expression and action in human multiple myeloma.

PURPOSE: Multiple myeloma (MM) is a clonal B-cell neoplasm. PC cell-derived growth factor (PCDGF) is a M(r) 88,000 glycoprotein growth factor. Our objective was to investigate the expression, function, and signaling pathways of PCDGF in human MM. EXPERIMENTAL DESIGN: PCDGF expression, function, and signaling pathways in human MM were studies using two human MM cell lines: ARP-1 and RPMI 8226. In addition, PCDGF expression in MM patients was examined using 13 human bone marrow biopsy samples. RESULTS: PCDGF mRNA and protein expression was detected in human MM cell lines such as ARP-1 and RPMI 8226. PCDGF added exogenously stimulated cell growth and sustained cell survival of both ARP-1 and RPMI 8226 cells in a dose- and time-dependent fashion. Conversely, treatment with neutralizing anti-PCDGF antibody inhibited the growth of RPMI 8226 cells suggesting that PCDGF acts as an autocrine growth factor for MM cells. Studies of signal transduction pathways showed PCDGF stimulated mitogen-activated protein kinase and phosphatidylinositol 3'-kinase pathways but not the Janus-activated kinase-signal transducer and activator of transcription pathway. Immunohistochemical analysis of bone marrow smears obtained from MM patients indicated that PCDGF expression was associated with myeloma cells from MM patients and correlated with the presence of MM disease. CONCLUSION: These data suggest that PCDGF is an autocrine growth factor in the cell growth and survival of human MM cells, and may be a potential candidate as a biomarker of MM cells.

Bone Marrow↗