Search PubMed⌕ Search

Biomedical subjects

Jun Hayashi

Publications and source records attributed to Jun Hayashi.

At least 37 records · Page 2Linked to original sources
PubMed2005

Efficacy of prolonged treatment following combination with ribavirin and interferon for chronic hepatitis type C: A pilot study.

The aim of the present study was to assess the efficacy of the prolonged interferon monotherapy following combination treatment. Seventy-six patients were enrolled. Of these, 7 were withdrawn while undergoing treatment with interferon combined with ribavirin, and 12 remained positive for HCV-RNA at the completion of the combination treatment. We studied 57 Japanese patients with chronic hepatitis C due to genotype 1b HCV of a high viral load. These patients tested negative for HCV-RNA at the completion of the combination treatment for 24 weeks. After the combination treatment, 29 patients of the prolonged treatment group successively received interferon-alpha monotherapy for 24 weeks, while 28 patients in the combination treatment alone group received no medication. The rate of a sustained virologic response (SVR) was higher in the prolonged treatment group (41%, 12/29) than in the combination treatment alone group (25%, 7/28), but not significantly. Patients who became HCV-RNA negative by 4 weeks after the start of the combination treatment showed an SVR rate of 86%. The prolonged treatment resulted in SVR in all five patients who newly became HCV-RNA negative at 12 weeks. In conclusion, the prolonged treatment was effective for patients who newly became HCV-RNA negative at 12 weeks.

Journal Article↗
PubMed2005

Medium calcium concentration determines keratin intermediate filament density and distribution in immortalized cultured thymic epithelial cells (TECs).

Isolation and culture of thymic epithelial cells (TECs) using conventional primary tissue culture techniques under conditions employing supplemented low calcium medium yielded an immortalized cell line derived from the LDA rat (Lewis [Rt1l] cross DA [Rt1a]) that could be manipulated in vitro. Thymi were harvested from 4-5-day-old neonates, enzymically digested using collagenase (1 mg/ml, 37 degrees C, 1 h) and cultured in low calcium WAJC404A medium containing cholera toxin (20 ng/ml), dexamethasone (10 nM), epidermal growth factor (10 ng/ml), insulin (10 mug/ml), transferrin (10 mug/ml), 2% calf serum, 2.5% Dulbecco's Modified Eagle's Medium (DMEM), and 1% antibiotic/antimycotic. TECs cultured in low calcium displayed round to spindle-shaped morphology, distinct intercellular spaces (even at confluence), and dense reticular-like keratin patterns. In high calcium (0.188 mM), TECs formed cobblestone-like confluent monolayers that were resistant to trypsinization (0.05%) and displayed keratin intermediate filaments concentrated at desmosomal junctions between contiguous cells. Changes in cultured TEC morphology were quantified by an analysis of desmosome/membrane relationships in high and low calcium media. Desmosomes were significantly increased in the high calcium medium. These studies may have value when considering the growth conditions of cultured primary cell lines like TECs.

Animals↗
PubMed2005

Prevalence of atopic dermatitis and serum IgE values in nursery school children in Ishigaki Island, Okinawa, Japan.

There have been many studies of the prevalence of atopic dermatitis (AD), but few population-based epidemiologic studies measure the prevalence in Japan among children aged 5 years and younger. We examined the prevalence of AD, serum total IgE levels and specific IgE antibodies to 10 common allergens among children in Ishigaki Island, Okinawa, Japan in 2001. We also obtained information on the predictability of the U.K. Working Party diagnostic questionnaire criteria for AD in this population. Five hundred and sixty five children aged 5 years and younger were enrolled in this study with informed consent from their parents. The questionnaire of the U.K. Working Party diagnostic criteria for AD was translated into Japanese, and the parents completed the questionnaire sheet. Physical examination and blood sampling were done for all children. Thirty-nine out of the 565 (6.9%) children were diagnosed with AD by physical examination. The total and specific IgE levels were significantly higher in the children with AD than in those without AD. High levels of total IgE were found in 33.3% of the children with AD. A specific IgE to one or more allergens was detected in 64.1% of children with AD. However, a substantial population of children without AD also had high levels of total IgE (12.7%) and a specific IgE to one or more allergens (30.2%), and the increment of total and specific IgE levels was significantly associated with age. The percentage of positive answers to the questionnaire of the U.K. Working Party diagnostic criteria for AD was significantly higher in children with AD (59.0%) than in children without AD (5.3%) (P<0.0001). Its specificity was 94.7%. The false negative rate was 41%. In conclusion, the prevalence of AD was relatively low in children in Ishigaki Island. High levels of total IgE were found in only one third of children with AD under 5 years of age. The Japanese translated form of the questionnaire of the U.K. Working Party diagnostic criteria for AD should be refined to improve its sensitivity.

Child, Preschool↗
PubMed2005

Amelioration of extrapontine myelinolysis and reversible parkinsonism in a patient with asymptomatic hypopituitarism.

A 37-year-old woman with a history of transphenoidal surgery and gamma knife treatment for prolactinoma was admitted because of pneumoniae with hyponatremia (Na 109 mmol/l). After the careful correction of the serum sodium level within 15 mmol/l/day, the patient developed parkinsonism. MRI of the brain disclosed a signal increase in the bilateral basal ganglias on T2-weighted images, a finding consistent with extrapontine myelinolysis (EPM). Interestingly, the parkinsonism fully disappeared after the replacement therapy of hydrocortisone for adrenal insufficiency due to hypopituitarism, and MRI 5 months later showed complete disappearance of the lesions, indicating the patient had ameliorated from the EPM.

Adult↗
PubMed2005

Chronic myelogenous leukemia that occurred two years after the diagnosis of adult Still's disease.

A 25-year-old Japanese man was diagnosed with steroid-resistant Adult Still's Disease (ASD) in August 2000. No evidence of chronic myelogenous leukemia (CML) had been found during admissions in 2000 and 2001. In August 2002, he was diagnosed with CML with a peripheral white blood count of 69,940/microl and positivity for Philadelphia chromosome and BCR/ABL fusion gene on bone marrow aspiration. No case of CML was reported to develop from ASD. Because a diagnosis of ASD is based on the exclusion of other diseases, we must be cognizant of the possibility of the development of concurrent diseases.

Adult↗
PubMed2005

Pravastatin improves insulin resistance in dyslipidemic patients.

To evaluate the effect of pravastatin on both lipid and glucose metabolism, twenty-two consecutive dyslipidemic patients treated with pravastatin at 10 mg/day for one year were enrolled in this study. The meal test, which consisted of 115 g of cookies (energy 560 kcal; glucose 75 g; protein 7 g; fat 24 g), was conducted before and after one year of treatment. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR), by the area under the IRI curve (AUC-IRI), and by the formula AUC-IRI x AUC-PG. After one year of treatment with pravastatin, the plasma glucose (PG), immunoreactive insulin (IRI) and C-peptide levels were unchanged after fasting and at 120 minutes after the meal test; however, PG, IRI and C-peptide levels at 60 minutes after the meal were all significantly decreased from baseline (p < 0.05). AUC-IRI and AUC-IRI x AUC-PG were also significantly decreased (p < 0.05). HOMA-IR was reduced by 26.8%, but the reduction was not significant. The triglyceride (TG) level was decreased after fasting and increased at 60 and 120 minutes after the meal test, but not significantly. This study demonstrated that pravastatin not only reduced serum lipids, but also improved the glucose metabolism, including insulin resistance, of dyslipidemic patients.

Aged↗
PubMed2004

Body surface area is an independent factor contributing to the effects of lamivudine treatment.

BACKGROUND:: It has been suggested that lamivudine therapy may be even more effective if administered at higher doses than is dictated by the current standard regimen. We analyzed the correlation between the effects of lamivudine and body surface area (BSA). METHOD:: We evaluated 134 patients with chronic hepatitis B who had been treated with lamivudine for more than 12 months. The effect of the treatment was evaluated from the levels of serum alanine aminotransferase (ALT) and HBV-DNA. Several variables that could influence the response to treatment, including ALT, albumin, and bilirubin levels, platelet counts, BSA, HBV-DNA, and HBeAg were analyzed. RESULTS:: Univariate logistic analysis selected platelet counts, BSA, HBV-DNA and HBeAg in the biological evaluation, and bilirubin, BSA, HBV-DNA and HBeAg in the virological evaluation (chi(2)>1.0). Using these factors, multivariate analysis revealed that BSA (chi(2)=12.8, p=0.0004) was the only factor that could contribute significantly to the improvement of ALT levels, and that BSA (chi(2)=4.4, p=0.0354) and HBeAg (chi(2)=8.1, p=0.0044) were independent factors that could influence the suppression of HBV-DNA. CONCLUSION:: We revealed that BSA is a significantly predictor of the effect of lamivudine therapy, suggesting that lamivudine dosage should be based on the individual BSA.

Journal Article↗
PubMed2004

Identification of non-phosphate-containing small molecular weight inhibitors of the tyrosine kinase p56 Lck SH2 domain via in silico screening against the pY + 3 binding site.

The protein p56 lymphoid T cell tyrosine kinase (Lck) is predominantly expressed in T lymphocytes where it plays a critical role in T-cell-mediated immune response. Lck participates in phosphotyrosine-dependent protein-protein interactions through its modular binding unit, the Src homology-2 (SH2) domain. Accordingly, virtual screening methods combined with experimental assays were used to identify small molecular weight nonpeptidic compounds that block Lck SH2 domain-dependent interactions. Virtual screening included scoring normalization procedures and postdocking structural clustering that is shown to facilitate the selection of active compounds. By targeting the well-defined hydrophobic binding pocket known to impart specificity on Lck-protein interactions (i.e., pY + 3 site), inhibitors of the Lck SH2 domain were discovered that omit the phosphotyrosine (pY) or related moieties. The 34 out of 196 computationally selected compounds were shown to inhibit Lck SH2 domain association with phosphorylated immunoreceptor tyrosine based activation motifs peptide. Twenty-four of the active compounds were further tested for their ability to modulate biological function. Thirteen of these compounds showed inhibitory activity in mixed lymphocyte culture assay. Fluorescence titration experiments on four of these active compounds further verified their binding to the SH2 domain. Because of their simple chemical structures, these small organic compounds have the potential to act as lead compounds for the development of novel immunosuppressant drugs.

Animals↗
PubMed2004

PC cell-derived growth factor mediates tamoxifen resistance and promotes tumor growth of human breast cancer cells.

PC cell-derived growth factor, also known as progranulin, is an M(r) 88,000 growth factor (referred as PCDGF/GP88) overexpressed in human breast cancer. Antisense inhibition of PCDGF/GP88 expression in MDA-MB-468 cells inhibited tumor formation in nude mice. In estrogen receptor-positive cells, PCDGF/GP88 was expressed in response to estradiol and shown to mediate its mitogenic effect. Pathologic studies indicated that PCDGF/GP88 was expressed in 80% of invasive ductal carcinomas in correlation with parameters of poor prognosis. In the present article, the relationship between PCDGF/GP88 expression and tamoxifen resistance was examined in MCF-7 cells. PCDGF/GP88 overexpression rendered MCF-7 cells able to proliferate in the absence of estrogen and in the presence of tamoxifen. The PCDGF/GP88-overexpressing cells formed tumors in ovariectomized nude mice in the absence of estradiol and in its presence, in contrast to MCF-7 cells. Tumor growth of the overexpressing cells was increased significantly when the mice were treated with tamoxifen. PCDGF/GP88 blocked tamoxifen-induced apoptosis by preventing down-regulation of bcl-2 expression and poly(ADP-ribose) polymerase cleavage. In addition, PCDGF/GP88-overexpressing cells presented higher level of the angiogenic factors vascular endothelial growth factor and angiopoietin-1 than MCF-7 control cells. Tamoxifen treatment additionally increased the level of vascular endothelial growth factor. These studies suggest that PCDGF/GP88 plays a critical role in breast cancer tumorigenesis and in the transition to estrogen independence and tamoxifen resistance, a hallmark of poor prognosis. On the basis of the in vivo studies, it is postulated that tamoxifen treatment of patients with estrogen receptor-positive breast tumors overexpressing PCDGF/GP88 could have adverse clinical consequences.

Animals↗
PubMed2004

Short-term interferon-alfa therapy for acute hepatitis C: a randomized controlled trial.

Acute hepatitis C often progresses to chronic infection. We undertook a randomized controlled trial to determine whether short-term therapy with interferon (IFN) during acute hepatitis C is effective in preventing the development of chronic hepatitis. Thirty patients with acute hepatitis C were randomized into 1 of 2 treatment groups. IFN therapy was initiated 8 weeks after the onset of acute hepatitis in the early-intervention group and after 1 year of observation in the late-intervention group. Short-term therapy consisted of natural IFN-alfa (6 million units) administered on consecutive days for a period of 4 weeks. Any signs of recrudescence of disease were immediately followed by interval IFN therapy (3 times weekly for 20 weeks). In the early-intervention group, short-term therapy was associated with a sustained virological response in 13 of 15 patients (87%). Follow-up treatment was associated with a sustained virological response in both of the remaining 2 patients (100%). The sustained virological response rate was significantly higher in the early-intervention group (87%, 13 of 15 patients after short-term therapy alone, and 100%, 15 of 15 patients after short-term with or without follow-up therapy) than in the late-intervention group (40%, 6 of 15 patients after short-term therapy alone, and 53%, 8 of 15 patients after short-term therapy with or without follow-up therapy, P =.021 and P =.006, respectively). In conclusion, short-term (4 weeks) IFN treatment of patients with acute hepatitis C may be associated with satisfactory results, if initiated at an early stage of the disease.

Acute Disease↗
PubMed2004

Downregulation of CXCR5 in CD27- B cells of HIV-1 infected patients.

The CD27(-) (naive) B cells of HIV-1 infected patients have been shown to be increased in frequency and to be activated, as indicated by high CD38 expression on the cell surface. CXCR5, a B cell chemokine receptor, is expressed on circulating CD27(-) (naive) B cells and plays a pivotal role in peripheral B cell development. To investigate the effect of HIV-1 infection on the expression of this chemokine receptor on naive B cells, the expression level of CXCR5 on CD27(-) B cells was examined in 19 drug-naive HIV-1 infected patients, 27 HAART-treated patients, and 20 controls. CXCR5 expression on CD27(-) B cells was significantly lower in drug-naive patients than in HAART-treated patients and controls (P < 0.01). CD27(-) B cells with high CD38 expression exhibited low CXCR5 expression. The CXCR5 expression level on CD27(-) B cells recovered to within the normal range after effective antiretroviral therapy. These findings suggested that HIV-1 infection induces a remarkable phenotypic alteration of naive B cells and that the activated naive B cells found in HIV-1 infection downregulate CXCR5 on their surface. Impaired homing of naive B cells may contribute to HIV-1 induced immunological deficiencies.

ADP-ribosyl Cyclase↗
PubMed2004

Carotid atherosclerosis and cardiovascular risk factors: a comparison of residents of a rural area of Okinawa with residents of a typical suburban area of Fukuoka, Japan.

Areas of Japan are known worldwide for the longevity of their residents. Okinawa has the highest longevity in Japan and a low rate of death due to cardiovascular disease. We investigated carotid atherosclerotic (CA) risk factors in islands of I city in Okinawa prefecture and compared them with K town, a suburban area of Fukuoka prefecture in Kyushu, to determine the relationship between cardiovascular risk factors and carotid atherosclerosis. We investigated conventional cardiovascular risk factors in 1078 I city residents (375 men, mean age 63.7 and 703 women, mean age 60.0) in 2000 and 2364 K town residents (676 men, mean age 57.1 and 1688 women, mean age 53.0) in 1999. Carotid atherosclerosis was assessed by mean intima-media thickness (IMT) by B-mode ultrasound. The mean IMT was significantly lower in the residents of I city than in those of K town (P < 0.05). Total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) levels and smoking rate were also lower in I city than in K town. Body mass index (BMI) and triglyceride (TG) level were higher in I city than in K town. In I city, multiple regression analysis found independent relationships between carotid atherosclerosis and age, sex (male), hypertension, LDL cholesterol, high-density-lipoprotein cholesterol (HDL-C), and diabetes. The lower mean IMT is probably related to a lower lifetime burden of atherosclerotic risk factors, which may in turn be related to the longevity of Okinawa residents. BMI was not a cardiovascular risk factor, although LDL cholesterol was a common important risk factor.

Adult↗
PubMed2004

The influence of lifestyle modification on carotid artery intima-media thickness in a suburban Japanese population.

To evaluate the influence of lifestyle modification with and without lipid-lowering drug therapy on the carotid arterial wall, we did a 2 year prospective ultrasound study of carotid intima-media thickness (IMT) in 1390 male and female residents of a suburban Japanese town. According to total cholesterol (TC) level at baseline, subjects were classified into a lifestyle modification alone group (TC >/= 220 mg/dl, n = 437), a lifestyle modification with lipid-lowering drug group (TC >/= 220 mg/dl, n = 159), and a control group (TC < 220 mg/dl, n = 794). After 2 years of follow-up, both sexes of both treatment groups showed significant reductions of TC, low-density lipoprotein cholesterol (LDL-C), and IMT, although TC continued over 220 mg/dl in some subjects in the lifestyle modification group. The reduction of TC and LDL-C was significantly higher in the lifestyle modification with lipid-lowering drug group than in the lifestyle modification alone group. Although the IMT reduction was not statistically different between the treatment groups of either sex, the reduction of IMT was greater in the lifestyle modification with lipid-lowering drug group than in the lifestyle modification alone group. Our results indicate that comprehensive lifestyle modification can reduce carotid IMT in the general population, with or without the use of lipid-lowering drugs and that cholesterol reduction is of benefit even when TC level remain above the recommended level.

Adult↗
PubMed2004

Fas ligand is enriched in the caveolae membrane domains of thymic epithelial cells.

Both Fas and Fas ligand (FasL) are expressed in the thymus. Although reports suggest that they are important throughout the thymocyte maturation process their precise role remains elusive. The present paper characterizes the expression of FasL in the thymus and in the TEA3A1 and BT1B functional thymic epithelial cell (TEC) lines. FasL expression by thymus fractions, TEA3A1, and BT1B cells was detected by Northern blot analysis. In TEA3A1 cells, we discovered that FasL protein expression was localized to caveolae membrane domains. This restricted subcellular localization of FasL, together with reports describing the localization of the major histocompatibility complex proteins, the T cell receptor and Fas to caveolae membrane domains, may provide a mechanism for the deletion of thymocytes during negative selection. Finally, using semi-quantitative RT-PCR we found that FasL expression by TECs is regulated by glucocorticoids.

Animals↗
PubMed2004

Efficacy of early retreatment with interferon beta for relapse in patients with genotype Ib chronic hepatitis C.

BACKGROUND: Interferon (IFN) retreatment for hepatitis C virus (HCV) relapsers has been effective under some conditions. We conducted a randomized, controlled trial of IFN beta retreatment for HCV relapsers after IFN alpha. PATIENTS AND METHODS: We gave IFN beta 6MIU therapy to 43 patients who had relapse of HCV after the 24 weeks IFN alpha monotherapy. The 43 patients were randomly assigned to two groups: Group A started retreatment within 4 weeks after relapse; and Group B started retreatment 24 weeks or more after relapse. RESULTS: Nine patients showed sustained virological response (SR) to the retreatment. All of these patients were in a low viral load subgroup. The SR rate in Group A (8/22, 36%) was significantly higher than in Group B (1/21, 5%) (P=0.0128). Among patients with lower viral load, the SR rate in Group A (8/10, 80%) was also significantly higher than in Group B (1/8, 13%) (P=0.0076). CONCLUSION: The retreatment with IFN beta is effective for patients with HCV low viral load, and the sooner after the relapse the retreatment is started, the better the clinical results will be.

Journal Article↗
PubMed2004

Maturation of monocyte-derived dendritic cells by Hochu-ekki-to, a traditional Japanese herbal medicine.

To investigate the immunological effect of the traditional Japanese herbal medicine (kampo), Hochu-ekki-to (HOT), on dendritic cells (DC), we examined in vitro if HOT would stimulate the maturation process of human monocyte-derived DC as do TNF-alpha and LPS. Monocytes from a healthy volunteer were cultured in the presence of IL-4 and GM-CSF, and the generated immature DC were stimulated with HOT, TNF-alpha, or LPS (HOT-DC, TNF-DC, and LPS-DC, respectively) for 2 days. Flow cytometric analysis showed that HOT stimulated DC to express the surface maturation markers CD80, CD83, and CD86 dose-dependently and that the up-regulation level was identical to TNF-alpha and LPS. The antigen-uptake capacity of HOT-DC was determined by FITC-labeled albumin uptake. HOT-DC lost albumin uptake capacity comparable to LPS-DC, indicating DC maturity. IL-12 (p70) production by HOT-DC and TNF-DC was not increased in comparison with LPS-DC. The antigen-presenting capacity of HOT-DC as analyzed by allogeneic T cell proliferation was significantly increased in comparison with immature DC and was identical to LPS-DC. These results demonstrate that HOT stimulates DC maturation as well as the other known maturation factors, despite low IL-12 production, and suggests the possibility that DC maturation by HOT can play an important role in the improvement of the immunoregulatory function in patients with impaired host defense.

Adult↗
PubMed2004

Confirmation of nosocomial hepatitis C virus infection in a hemodialysis unit.

OBJECTIVES: To investigate a hepatitis C virus (HCV) outbreak in a hemodialysis unit and determine the source of transmission. METHODS: We have prospectively investigated the epidemiology of hemodialysis-related HCV infection in a single unit since 1989. In September 2000, acute hepatitis C (AH-C) was diagnosed in 5 patients by alanine aminotransferase elevation and HCV genotype 1b viremia without antibody to HCV. We surveyed the epidemiologic situation and performed polymerase chain reaction sequence analysis of the HCV 5'-noncoding (5'NC) region in the patients for comparison with 9 patients with chronic HCV genotype 1b viremia. RESULTS: Sequence analysis of the 5'NC region showed the consistency in the 5 independent clones from each AH-C patient and those from each chronic HCV viremia patient and no quasispecies over time in the clones of any of 14 analyzed patients. All AH-C patients had the same sequencing of the 6 variations in the region with the only other patient. A saline ampoule, used for heparin solution during hemodialysis, had a recap function. It was difficult to determine whether the ampoule was new or had already been used. The source-patient often underwent hemodialysis before the AH-C patients and most of their hemodialysis-related medicine was prepared during the source-patient's treatment. These findings suggested a high possibility that the AH-C patients shared a single heparin-saline solution ampoule contaminated by HCV from the source-patient. CONCLUSION: Nosocomial HCV infection occurred as a result of poor infection control practice when a patient with chronic HCV viremia received treatment prior to other hemodialysis patients.

Acute Disease↗