Biomedical subjects

Jun Hayashi

Publications and source records attributed to Jun Hayashi.

At least 19 recordsLinked to original sources

PubMed2006

A comparison of the antitumor effects of interferon-alpha and beta on human hepatocellular carcinoma cell lines.

The antiviral, antiproliferative and immunomodulatory effects of type I interferons (IFNs) are well documented, however, few studies have been published concerning differences in the antitumor effects of IFN-alpha and beta. In the present study, differences in antitumor effect, including the antiproliferative effect, cell cycle change, apoptosis, and the IFN-stimulated gene (ISG) were examined by flow cytometry between IFN-alpha and beta on three human hepatocellular carcinoma (HCC) cell lines (HepG2, Huh7 and JHH4). The antiproliferative effect of both IFNs on the HCC cell lines was time- and dose-dependent, and IFN-beta was significantly stronger than IFN-alpha. The cell cycle effect by both IFNs was an S-phase accumulation, with IFN-beta having a tendency to increase the S-phase ratio more strongly than IFN-alpha, especially in Huh7. Apoptosis marker expression, Fas antigen and intracellular active caspase-3, was increased after the addition of IFNs, especially of IFN-beta. The expression of human leukocyte antigen-class I molecules, ISG-encoded protein, was increased after the addition of IFNs, especially of IFN-beta. These data suggest that IFN-beta has a greater antitumor effect than IFN-alpha on HCC of a very early stage in patients with chronic hepatitis C.

Antineoplastic Agents↗

PubMed2006

Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2: a project of the Kyushu University Liver Disease Study Group.

AIM: To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus (HCV) of genotype 2, a multi-center study was retrospectively analyzed. METHODS: In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. RESULTS: The overall sustained virological response (SVR), defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, (146/173) by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin (46.9% vs 92.9%), but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment (34.8% vs 92.0%). CONCLUSION: The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16 weeks.

Adult↗

PubMed2006

Long-term lamivudine treatment for chronic hepatitis B in Japanese patients: a project of Kyushu University Liver Disease Study.

AIM: To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B. METHODS: In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 (median 21) mo. Virological response was a decline to a serum HBV DNA level less than 3.7 log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment. RESULTS: Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8 log copies/mL (P<0.0001), HBeAg negativity (P<0.0001), a platelet count of 100 x 10(9)/L or more (P=0.0162) at baseline, and a decline of the HBV DNA level of more than 3.2 log copies/mL as compared with the baseline level at 3 mo after the start of treatment (P=0.0003) to be significantly associated with virological response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded virologically at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5% of 51 patients at 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at >=5 mo. A virological breakthrough was found significantly more often in patients with delayed virological response. CONCLUSION: Lamivudine treatment could suppress serum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBeAg at baseline, in the absence of cirrhosis, and in patients with a decline in HBV DNA level soon after the start of treatment.

Adult↗

PubMed2006

PC cell-derived growth factor confers resistance to dexamethasone and promotes tumorigenesis in human multiple myeloma.

PURPOSE: We have shown previously that the 88 kDa glycoprotein PC cell-derived growth factor (PCDGF/GP88) is expressed and acts as an autocrine growth factor in human multiple myeloma cells. The present study investigates whether PCDGF/GP88 expression in multiple myeloma cells leads to the development of resistance to dexamethasone, a conventional drug for multiple myeloma patients. EXPERIMENTAL DESIGN: PCDGF functions and signaling pathways in dexamethasone-induced apoptosis were studied using a representative dexamethasone-sensitive multiple myeloma cell line ARP-1. The effect of PCDGF/GP88 was further confirmed in PCDGF/GP88-overexpressed ARP-1 cells. RESULTS: Dexamethasone inhibits cell growth and induces apoptosis in a time- and dose-dependent fashion. Exogenous addition of PCDGF/GP88 to the ARP-1 cells prevented dexamethasone-induced apoptosis as examined by flow cytometry analysis and poly(ADP-ribose)polymerase cleavage assay. Signaling studies showed that mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and nuclear factor-kappaB were involved in the antiapoptotic effect of PCDGF/GP88. Overexpression of PCDGF/GP88 in ARP-1 cells rendered the cells refractory to dexamethasone-mediated apoptosis, enhanced their ability to form colonies in soft agar, and to form tumors in vivo without any change in glucocorticoid receptor expression and function. CONCLUSION: These data suggest that expression of PCDGF/GP88 confers resistance to dexamethasone and increase tumorigenesis of multiple myeloma cells in mouse xenografts. Our data here also raises the possibility of PCDGF/GP88 as a potential therapeutic target for dexamethasone-resistant multiple myeloma.

Antineoplastic Agents↗

PubMed2006

[Varicella-zoster virus symptoms and polyneuropathy in a patient with human immunodeficiency virus infection not improved until highly active anti-retroviral therapy added to acyclovir therapy].

In March 2003, a 34-year-old man with left facial palsy, dysphagia, and hoarseness treated with acyclovir suffered worsened dermatological and neurological problems. A routine blood test in early April showed the patient to be HIV-antibody positive, so he was transferred to our hospital. Blood analysis showed serum HIV-RNA at 96,000 copies/mL and a CD 4 count of 170/microL. Brain MRI taken on admission showed a T 2 high lesion in their left medulla. Acyclovir was thought to be ineffective due to reduced cell-mediated immunity because of the HIV infection, and HAART therapy was begun. After two months of HAART, skin lesions and the T 2 high lesion in left medulla improred. HIV-RNA became undetectable and the CD 4 count exceeded 500/microL. Intracellular cytokine analysis by flow cytometry showed a shift from Th 2 to Th 1 dominance. The elimination of VZV may thus have been promoted by the combination of acyclovir and HAART.

Acyclovir↗

PubMed2006

[Pseudomembranous colitis after Helicobacter pylori eradication therapy].

A 69-year-old woman with gastritis was prescribed a 1-week triple regimen therapy of Amoxicillin, Clarithromycin, and Lansoprazole to eradicate Helicobacter pylori (H. pylori) starting on March 7, 2005. H. pylori was detected on the gastric mucosa by the urease test. Twenty days after eradication therapy, she began to suffer from profuse watery diarrhea. Colonoscopy on April 12 showed multiple pseudomembranes in the cecum and the transverse colon, leading to a diagnosis of pseudomembranous colitis. Because she had not taken Vancomycin (VCM) (500 mg/day) as directed, she had a relapse of watery diarrhea and was admitted on April 30. A stool test for Clostridium difficile (CD) toxin was positive, although colonoscopy showed only a few aphthoid erosions in the cecum and the transverse colon on May 6. She was treated with oral VCM (2000 mg/day) from May 6, and diarrhea disappeared by May 11. The stool test for CD toxin was negative, so VCM was discontinued. Care must thus be taken in H. pylori eradication to ensure that the triple regimen therapy does not lead to pseudomembranous colitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2006

Effect of probucol on elderly hypercholesterolemic patients in the FAST study.

The present study involved a detailed post hoc comparison of the efficacy and safety of lipid-lowering therapy in elderly hypercholesterolemic patients from the Fukuoka Atherosclerosis Trial (FAST). The FAST cohort of 246 hypercholesterolemic patients included 76 patients who were (75 years old. Patients were randomized to receive probucol (500 mg/day) or pravastatin (10 mg/day) therapy, or to a control group (diet alone), and then were followed for 2 years. In patients > or = 75 years old, either probucol or pravastatin achieved a significant reduction of carotid intima-media thickness (IMT). In patients <75 years old, lipid-lowering therapy also achieved a significant reduction of IMT. In patients > or = 75 years old receiving probucol, the relative risk (95% confidence interval) of all-cause mortality was 0.15 (0.02 to 1.28) and that for major coronary events was 0.12 (0.02 to 1.04). In conclusion, probucol reduced the incidence of cardiovascular disease in elderly hypercholesterolemic patients as well as younger patients.

Adult↗

PubMed2006

Both hepatitis C virus and Chlamydia pneumoniae infection are related to the progression of carotid atherosclerosis in patients undergoing lipid lowering therapy.

Recent experimental and epidemiological findings suggest that infectious agents may play a role in the development and progression of atherosclerosis. We previously reported that Chlamydia pneumoniae (C. pneumoniae) infection reduces the effectiveness of lipid-lowering therapy for carotid atherosclerosis and that this micro-organism may play a role in the progression of atherosclerosis. In this study, we investigated the possible association between hepatitis C virus (HCV) infection and carotid arteriosclerosis. A total of 165 asymptomatic hypercholesterolemic patients were randomized to receive probucol (500 mg/day, n=82) or pravastatin (10 mg/day, n=83) and were followed for 2 years. The 2-year change of the maximum common carotid artery intima-media thickness (Max-IMT) was the primary endpoint, while the Max-IMT and the incidence of major cardiovascular events were secondary endpoint. All serum samples were tested for antibody to HCV (anti-HCV) by enzyme-linked immunosorbent assay (ELISA), and all anti-HCV-positive samples were assayed for HCV RNA. Patients without HCV infection (n=25) showed a significant reduction of Max-IMT (-10.9%) (p<0.0001), while a small decrease of Max-IMT was noted in the patients with HCV infection (n=25) (-0. 3%). Significant differences in the reduction of serum total cholesterol and LDL cholesterol were found between patients with and without HCV infection (both p<0.0001). No significant difference in therapeutic effect was noted between the probucol and the pravastatin groups. After adjustment for confounding risk factors, both C. pneumoniae infection and anti-HCV positivity were associated with a greater risk of an increase in Max-IMT (8.5635 [1.3738-15.7532], p<0.05, 9.5040 [0.2886-18.7194], p<0.05, respectively). These findings suggest that both chronic HCV infection and C. pneumoniae infection can reduce the effectiveness of lipid-lowering therapy for carotid atherosclerosis, and that the HCV may play a role in the progression of atherosclerosis in HCV infected patients.

Adult↗

PubMed2006

Impact of peripheral arterial disease and acute ischemic stroke.

Peripheral arterial disease (PAD) is associated with coronary artery disease (CAD) and stroke, but data on the relationship between PAD and acute ischemic stroke are lacking. Therefore, we investigated this relationship. A total of 101 patients were enrolled on admission to Harasanshin General Hospital (Fukuoka, Japan) with their first ischemic stroke. All 101 patients underwent cranial CT and/or brain magnetic resonance imaging, duplex ultrasonography of the extracranial carotid arteries, and transthoracic echocardiography. The subjects were aged 41 to 92 years. PAD was present in 81/101 patients (80.2%), including 57/73 (78.1%) with small artery occlusion, 11/13 (84.6%) with large artery occlusion, and 13/15 (86.7%) with cardiogenic embolism. In 42 of these 81 patients (51.9%), PAD was asymptomatic. Serum apoprotein A1 levels were significantly higher and the intima-media thickness was significantly greater in the patients with PAD than in those without PAD. The modified Rankin scale score was significantly higher on admission in patients with PAD than in those without PAD. Stepwise logistic regression analysis revealed that the apoprotein A1 level and the modified Rankin scale score on admission were strongly associated with the occurrence of stroke in patients with PAD. Our results suggest that PAD is frequently associated with acute ischemic stroke. It may be important to perform screening for PAD in patients who have suffered an ischemic stroke.

Adult↗

PubMed2005

Relationship between body surface area and ALT normalization after long-term lamivudine treatment.

AIM: To further evaluate the relationship between BSA and the effects of lamivudine in a greater number of cases and over a longer period of observation than in our previous evaluation. METHODS: We evaluated 249 patients with chronic hepatitis B. The effects of treatment for one year (n = 249), two years (n = 147), and three years (n = 72) were evaluated from the levels of serum ALT and HBV-DNA, as biological and virological effects (undetectable levels by PCR), respectively. Moreover, several variables that could influence the response to treatment, including ALT, albumin, bilirubin, platelet counts, BSA, HBV-DNA, and HBeAg were analyzed. RESULTS: For 1-year treatment, multivariate analysis revealed that BSA (P = 0.0002) was the only factor for the biological effect, and that ALT (P = 0.0017), HBV-DNA (P = 0.0004), and HBeAg (P = 0.0021) were independent factors for the virological effect. For 2-year treatment, multivariate analysis again showed that BSA (P = 0.0147) was the only factor for the biological effect, and that ALT (P = 0.0192) and HBeAg (P = 0.0428) were independent factors for the virological effect. For 3-year treatment, multivariate analysis, however, could not reveal BSA (P = 0.0730) as a factor for the normalization of ALT levels. CONCLUSION: BSA is a significant predictor for the normalizing the effect of lamivudine therapy on ALT for an initial 2-year period, suggesting that lamivudine dosage should be based on the individual BSA.

Adolescent↗

PubMed2005

Association between fast-migrating low-density lipoprotein subfraction as characterized by capillary isotachophoresis and intima-media thickness of carotid artery.

BACKGROUND: A mildly modified LDL subfraction that is characterized by an increased negative charge exists in plasma. This electronegative LDL separated by ion-exchange chromatography has been shown to be inflammatory and its proportion is increased in patients with hyperlipidemia and diabetes mellitus. The present study examined the association between the level of fast (f)-migrating LDL subfraction characterized by capillary isotachophoresis (cITP) and carotid-artery intima-media thickness (CA-IMT). METHODS AND RESULTS: This study included 469 subjects who underwent a physical examination. CA-IMT was determined by high-resolution B-model ultrasonoraphy. Levels of charge-based LDL subfractions were measured by cITP on a Beckman P/ACE MDQ system. An increased serum LDL-C level and cITP fLDL level were associated with increased CA-IMT after adjusting for age. The extent of the associations between cITP fLDL and CA-IMT and between LDL-C and CA-IMT were similar as assessed by a receiver-operating characteristic curve analysis. LDL-C, triglyceride, and remnant-like particle cholesterol levels were independently correlated with cITP fLDL, and the LDL-C level had the strongest correlation with cITP fLDL. The association between the cITP fLDL level and CA-IMT was significant in the high LDL-C stratum but not in the low stratum, indicating that it is modified by the LDL-C level. The high-LDL-C-high-fLDL group had the highest relative risk for a high CA-IMT among the groups with each combination of LDL-C and cITP fLDL level. CONCLUSION: The cITP fLDL level was associated with CA-IMT and its combination with the LDL-C level is a stronger indicator for a high CA-IMT.

Adult↗

PubMed2005

Interferon-alpha/beta upregulate IL-15 expression in vitro and in vivo: analysis in human hepatocellular carcinoma cell lines and in chronic hepatitis C patients during interferon-alpha/beta treatment.

Type I interferon (IFN) possesses antiviral and antitumor activities and also having an immune regulatory effect, activating cellular immune response and upregulating several cytokines. Recent study has shown that type I IFN upregurates the dendritic cell production of IL-15 capable of activating natural killer cells and CD8+ memory T lymphocytes. However, it is still unknown if type I IFN induces IL-15 production in non-immune cells and if type I IFN affects IL-15 production in vivo. The present study investigated the effect of type I IFNs on IL-15 expression in hepatocellular carcinoma (HCC) cell lines in vitro and in patients with chronic hepatitis C in vivo. When three HCC cell lines, Huh7, HepG2, and JHH4 were cultured in vitro, IFN upregulation of IL-15 expression was observed at both the mRNA and protein levels. In experiments using Huh7 cells, upregulation of IL-15 expression occurred within 24 h of the start of IFN stimulation, and both IFN-alpha and -beta dose-dependently increased IL-15 production in the range from 100 U/ml to 10,000 U/ml of concentration. IFN-beta showed stronger activity in IL-15 production induction in vitro than IFN-alpha. For in vivo examination, sera were obtained from 21 chronic hepatitis C patients treated with IFN and 29 healthy individuals, and the serum IL-15 level was quantified by ELISA. The serum IL-15 level of chronic hepatitis C patients before IFN treatment was similar to that of the healthy controls and significantly increased only during the IFN administration period. These results confirm that IFN-alpha/beta induce IL-15 production and also suggest that IL-15 may be associated with type I IFN-induced immune response.

Adult↗

PubMed2005

CD27(+) (memory) B cell decrease and apoptosis-resistant CD27(-) (naive) B cell increase in aged humans: implications for age-related peripheral B cell developmental disturbances.

To investigate age-related alterations in human humoral immunity, we analyzed the quantity and quality of peripheral B cell subsets, CD27-negative (CD27(-)) and CD27-positive (CD27(+)) B cells, by flow cytometry analysis in 54 aged individuals (mean age +/- SE, 74.6 +/- 0.7 years) and 30 young individuals (mean age +/- SE, 26.1 +/- 0.5 years). CD27(-) and CD27(+) B cells are regarded as naive and memory B cells, respectively. CD38, Ki-67, CD95 and bcl-2 were used as activation, proliferation and apoptotic markers. Susceptibility to apoptosis was evaluated by cell size and annexin-V binding in culture cells. The percentage of CD27(+) B cells was significantly lower in aged (mean, 19.2%) individuals than that in young individuals (mean, 28.2%). The opposite was true for CD27(-) B cells (mean, 80.8% in aged and 71.8% in young) (P < 0.01). The absolute number of CD27(+) B cells in aged individuals was significantly less than the number of CD27(-) B cells. The CD27(+) B cells from aged individuals showed little susceptibility to apoptosis, although CD95 expression on the CD27(+) B cells was significantly higher in the aged individuals than in the young individuals (P < 0.05). The CD38 and bcl-2 expression on the CD27(-) B cells was significantly higher in the aged individuals than in the young individuals (P < 0.05). In addition, the CD27(-) B cells from the aged individuals showed a decreased susceptibility to apoptosis compared with that of the young individuals. These findings suggested that human aging leads to both quantitative and qualitative alterations in the peripheral B cell developmental system, including memory and naive B cell balance and their surface phenotypes.

ADP-ribosyl Cyclase↗

PubMed2005

Kinetic analysis of Mycobacterium tuberculosis-specific cytokine production by PBMC in adults after BCG vaccination.

Although bacille Calmette-Guerin (BCG) has been used worldwide as the only vaccine for tuberculosis, its protective efficacy in human adults is controversial. To investigate human immunological responses to Mycobacterium tuberculosis after BCG vaccination, we analyzed IFN-gamma and IL-10 production by peripheral blood mononuclear cells (PBMC) from health-care workers five times throughout the year after BCG vaccination. Of 449 health-care workers, 36 (8.0%) were negative by the tuberculin skin test, and of these, 20 were vaccinated with BCG. Because all the subjects had received BCG vaccination as infants, the present vaccination was considered to be a revaccination. The cytokine responses of the vaccinated and control tuberculin skin-test-positive subjects (n = 6) were followed at 0, 2, 4, and 8 weeks and at 12 months. The mean IFN-gamma production by PBMC when cultured with purified protein derivative (PPD) gradually increased, reached a peak at week 8, and then declined until 12 months, with four exceptions who showed no IFN-gamma elevation. The IFN-gamma level of the vaccinated group at week 0 was significantly lower than that of the controls. The mean IL-10 production in response to PPD reached a peak at week 2, and then declined to its lowest point at week 8. These results indicate that the BCG vaccine can induce a type I cytokine response to M. tuberculosis in most tuberculin skin-test-negative adults at week 8, suggesting the immunological efficacy of vaccination.

Adolescent↗

PubMed2005

Serum antibody response to tuberculosis-associated glycolipid antigen after BCG vaccination in adults.

Tuberculous glycolipid antigens (TBGLs) are derived from the cell walls of Mycobacterium tuberculosis. Detection of anti-TBGL antibody in serum has recently become possible for the serodiagnosis of active tuberculosis. TBGL is not indigenous to M. tuberculosis, but it is widely found in Mycobacterium species. To elucidate the influence of M. bovis bacille Calinette-Guérin (BCG) vaccination, we assayed serum anti-TBGL antibody after BCG vaccination in adults. BCG vaccination was done for 20 Japanese healthcare workers with a negative tuberculin skin test reaction, and serum was collected 0, 2, 4, and 8 weeks and 1 year after vaccination. The tuberculin skin test became positive in 85% of the subjects. The mean anti-TBGL antibody titer remained negative throughout the observation period, but was elevated significantly compared with the pre-vaccination level, peaking at week 4 and showing a reduced level 1 year post-vaccination. These results showed that serological diagnosis using anti-TBGL antibody was not influenced by prior BCG vaccination.

Adult↗

PubMed2005

Strenuous physical labor is important as a cause of elevated alanine aminotransferase levels in Japanese patients with chronic hepatitis C viremia.

To clarify the influence of lifestyle habits on the elevated alanine aminotransferase (ALT) levels deterioration of Japanese patients with chronic hepatitis C virus (HCV) viremia, we investigated the effects of smoking, drinking, and physical labor on the disease course of the residents living in a rural area of Kyushu, Japan. The data of patients with chronic HCV viremia and control subjects without HCV infection were analyzed retrospectively from 1986 to 1992 and prospectively from 1993 to 2000. In 2000, a questionnaire was given to 268 HCV-infected patients and 275 control subjects to survey for the lifestyle habits. The data of serial ALT level testing during the observation period was used as a measure of liver damage: 183 HCV patients (68.3%) and 10 control subjects (3.6%) had abnormal ALT levels greater than 35 IU/1 for more than half of their observation period. The percentage of HCV patients with elevated ALT levels significantly increased with the daily consumption of alcohol (p < 0.0001), the length of time spent in strenuous physical labor per day (p = 0.0056), and the number of cigarettes smoked per day (p = 0.0003). A stepwise logistic regression analysis showed male sex (p = 0.003), platelet counts (p < 0.001), strenuous physical labor (p = 0.002), and drinking history (p = 0.007) to be significantly associated with the elevated ALT levels of HCV patients. When strenuous physical labor was done for over 2 h, the probability of elevated ALT levels was increased compared with patients engaging in strenuous physical labor under 2 h (estimated odds ratio = 1.82 [under 2 h], 20.60 [over 2 h]). Interestingly, strenuous physical labor was extracted before alcohol consumption as a significant factor in the elevated ALT levels. Among the control subjects, only the amount of alcohol consumed per day (p = 0.0001) was significantly associated with the elevated levels. These data suggests that strenuous physical labor over a long period of time might be related to elevated ALT levels in patients with chronic HCV viremia as well as drinking.

Adult↗

PubMed2005

Helper T cell cytokine response to ribavirin priming before combined treatment with interferon alpha and ribavirin for patients with chronic hepatitis C.

The viral genotype and serum viral level influence the response to interferon (IFN) treatment in patients with chronic hepatitis C virus (HCV) viremia. The aim of this study was to investigate a possible relationship between early virological response and helper T (Th) cell cytokine expansion by 4 weeks of ribavirin (RIB) alone followed by IFN and RIB combined in patients with genotype 1b and a high HCV RNA level, patients reported not to respond well to IFN treatment. Eighty-one patients with genotype 1b and a high HCV RNA level, over 100 international unit per milliliter (KIU/mL) (by Amplicor HCV Monitor), were assigned to two groups: Group A (N = 40) with a 4-week RIB administration followed by a 24-week combination treatment, and Group B (N = 41) with a 24-week combination treatment only. Blood was obtained from each patient on the following schedule: at Baseline (4 weeks before day 0), on day 0 (initiation day of the RIB and IFN combination treatment), weeks 4 (4 weeks after the start of the combination treatment), and at the end of the combination treatment. Flow cytometry was used to investigate sequential changes of IFN-gamma producing (Th1) and interleukin-4 producing (Th2) cells from whole blood samples after stimulation with PMA and ionomycin. Serum HCV RNA clearances were 32.5% at week 4, 43.2% at week 8, 85.7% at the end of the combination treatment, and 22.9% within the 24-week follow-up in Group A; and 17.1%, 27.0%, 66.7% and 19.4% in Group B, respectively. The mean Th1/Th2 ratio significantly increased from 15.9 at baseline to 17.6 at day 0 with a decrease of Th2 cells, and then significantly decreased from 17.6 at day 0 to 15.5 at week 4 in Group A, while there was no significant change in Group B between baseline and day 0. In Group A, 13 patients with HCV RNA clearance within 4 weeks had a significantly increased Th1/Th2 ratio, from 14.0 at baseline to 22.1 at day 0, and then a significantly decreased ratio, from 22.1 at day 0 to 15.0 at week 4, while the others had no significant change in the ratio. RIB administration preceding combined treatment of RIB with IFN was more effective in Th2 cell expansion than the usual combined treatment of IFN with RIB and led to a relatively early virological clearance in chronic hepatitis C patients with genotype 1b and a high HCV RNA level.

Adult↗

PubMed2005

Association between chronic Helicobacter pylori infection and acute ischemic stroke: Fukuoka Harasanshin Atherosclerosis Trial (FHAT).

Helicobacter pylori (H. pylori) have been associated both epidemiologically and pathogenetically with coronary atherosclerosis, but data on the relationship between chronic H. pylori infection and stroke are lacking. Therefore, we investigated the relationship between H. pylori infection and acute ischemic stroke in 62 patients with their first stroke and 143 controls. The stroke patients were all admitted to Harasanshin General Hospital (Fukuoka, Japan) and the controls were asymptomatic age-matched outpatients with hyperlipidemia who did not have cardiac disease or infections. All patients underwent cranial CT scanning and/or brain magnetic resonance imaging, duplex ultrasonography of the extracranial carotid arteries, and transthoracic echocardiography. H. pylori infection was diagnosed by detection of anti-H. pylori IgG antibodies, the 13C-urea breath test, and histology. Conditional logistic regression analysis was performed to analyze the data. The 62 stroke patients and 143 controls were aged from 41 to 92 years. Chronic H. pylori infection was associated with a higher risk of stroke due to small artery occlusion (odds ratio: 9.68; 95% CI: 3.56-33.08, P <0.001) and a lower risk of cardioembolic stroke (odds ratio: 0.27; 95% CI: 0.03-1.53). Chronic H. pylori infection still showed an overall association with ischemic stroke (odds ratio for all subtypes combined: 2.57; 95% CI: 1.09-6.08) after adjusting for major cardiovascular risk factors. These results suggest that chronic H. pylori infection may be a triggering factor that increases the risk of acute ischemic stroke.

Aged↗