Biomedical subjects

Jun Hayashi

Publications and source records attributed to Jun Hayashi.

72 records · Page 4Linked to original sources

PubMed2003

Poorly differentiated adenocarcinoma with signet-ring cells of the Vater's ampulla, without jaundice but with disseminated carcinomatosis.

A 49-year-old man was hospitalized because of a 2-month history of purpura in his extremities and for back pain. Laboratory findings showed alkaline phosphatase to be greatly elevated, and platelet counts and coagulation factor showed that the patient had disseminated intravascular coagulation (DIC). Compression fractures of the thoracic vertebrae were found on radiological examination. The histological findings from bone marrow showed metastasis of adenocarcinoma with signet-ring cells, although the primary site was unknown. To reduce tumor cells in number and improve DIC, 11 cycles of 5-Fluorouracil and leucovorin therapy were done, and the patient survived for 12 months. Autopsy showed a 0.8 cm diameter, poorly differentiated adenocarcinoma with the signet-ring cell type in the lamina propria of the Vater's ampulla. Many metastatic foci and micro tumor emboli were found in the lung and in bone marrow. The sections of the stomach, the gallbladder, urinary bladder, prostate, and thyroid gland showed no malignant cells. These findings suggest that the origin of the cancer may have been located in the Vater's ampulla. This is a rare case of an ampullary tumor of poorly differentiated adenocarcinoma with the signet-ring cell type, without jaundice but with multiple metastasis. 5-Fluorouracil and leucovorin were effective for increasing survival time and improving quality of life.

Ampulla of Vater↗

PubMed2002

Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia. Fukuoka Atherosclerosis Trial (FAST).

OBJECTIVES: This study investigated the effect of reducing serum lipids on carotid artery intima-media thickness (IMT) in asymptomatic patients with hypercholesterolemia from Fukuoka, Japan. BACKGROUND: Carotid atherosclerosis is a strong, independent predictor of morbidity and mortality in patients with coronary heart disease (CHD). METHODS: A total of 246 asymptomatic hypercholesterolemic patients (mean age 66 years) were randomized to receive either probucol (500 mg/day, n = 82) or pravastatin (10 mg/day, n = 83) or to enter a control group (diet alone, n = 81); they were followed for two years. The change in IMT in the common carotid artery was the primary end point measure, and the incidence of major cardiovascular events was the secondary measure. RESULTS: Over the two-year period, serum low-density lipoprotein (LDL) cholesterol was significantly reduced in the pravastatin group (36%), the probucol group (29%) and the control group (12%) (p < 0.0001, p < 0.0001 and p < 0.05, respectively). After two years, the probucol and pravastatin groups showed a significant reduction in IMT (-13.9% and -13.9% and p < 0.01 and p < 0.01, respectively), but there was significant IMT thickening (23.2%; p < 0.05) in the control group. Probucol reduced the rate of IMT increase, independently of its reduction of LDL or high-density lipoprotein cholesterol. Moreover, there was a significantly lower incidence of cardiac events in the probucol group (2.4%) than in the control group (13.6%) (p = 0.0136). CONCLUSIONS: Probucol reduced cholesterol levels and stabilized plaque, leading to a lower incidence of cardiac events in these hypercholesterolemic patients.

Adult↗

PubMed2002

Increased frequency of IFN-gamma-producing peripheral CD8+ T cells with memory-phenotype in patients with chronic hepatitis C.

To identify the capacity for cytokine production and the phenotypic characteristics of peripheral CD8(+) T cells in patients with chronic hepatitis C, 31 patients with chronic hepatitis C and 22 healthy controls were studied at the single cell level by three-color flow cytometry. Whole blood was stained with surface CD8, intracellular interferon-gamma (IFN-gamma), and interleukin-4 (IL-4), surface CD8, CD28, and intracellular IFN-gamma after stimulation with PMA plus ionomycin, and then surface CD8, CD45RA, and CD28. IFN-gamma-producing peripheral CD8(+) T cells were found frequently in patients than in controls (P < 0.05), whereas IL-4-producing peripheral CD8(+) T cells were not. Although the frequency of peripheral CD28(+)CD8(+) and CD28(-)CD8(+) T cells in patients was not different from that of controls, CD28(+)CD8(+) T cells exceeded CD28(-)CD8(+) T cells in the capacity for IFN-gamma-production after mitogenic stimulation (P < 0.01). In a more detailed analysis of the CD28(+)CD8(+) T cells, CD45RA(-)CD28(+)CD8(+) T cells, defined phenotypically as memory cells, were found frequently in patients than in controls (P < 0.05). There were no significant correlations between the frequency of IFN-gamma-producing peripheral CD8(+) T cells and hepatitis C virus RNA level or serum alanine aminotransferase level in patients. These data suggest that functionally T cytotoxic type 1 and memory CD8(+) T cells are predominant in the peripheral blood of chronic hepatitis C patients and that such activated CD8(+) T cells are associated with liver damage.

Adult↗

PubMed2002

A patient with primary human immunodeficiency virus infection for whom highly active antiretroviral therapy was successful.

We report the case of a 25-year-old male Japanese homosexual with primary human immunodeficiency virus (HIV)-1 infection and early stage syphilis. Approximately 60 days after HIV exposure by sex with another man, the patient abruptly had high fever, after which he experienced a variety of severe, prolonged symptoms such as painful oral mucosa ulcerations, rash, lymphadenopathy, splenomegaly, and a 5.5-kg weight loss. Serum lactate dehydrogenase and liver biochemical test values were elevated. Antibodies to HIV by both enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) test were negative at the time of symptom onset, but serum HIV-1 RNA level was 1 585 000 copies/ml. Antibody seroconversions were found on day 9 after the onset of symptoms by ELISA and on day 16 by WB test, suggesting primary HIV infection. Within 2 weeks of starting highly active antiretroviral therapy (HAART), all symptoms except lymphadenopathy were resolved, and the serum HIV-1 RNA level dramatically decreased to 5011 copies/ml, eventually becoming undetectable by the standard method. The patient has remained asymptomatic for the 18 months since symptom resolution after HAART, and HIV-1 RNA remains undetectable.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Chlamydia pneumoniae seropositivity and early carotid atherosclerosis in a suburban Japanese population.

To evaluate the association between Chlamydia pneumoniae (C. pneumoniae) infection and carotid atherosclerosis (CA), we investigated CA assessed by carotid B-mode ultrasound and known or suspected atherosclerotic risk factors including C. pneumoniae IgG and IgA antibodies in 2410 residents (mean age 54.5+/-13.6 years, 697 men) of a suburban Japanese town. CA was found in 30.1% of men and in 14.0% of women, IgG in 59.4% and in 51.4%, and IgA in 36.9% and in 32.4%, respectively. In univariate analysis, most conventional atherosclerotic risk factors and IgA antibody were significantly associated with CA in both sexes, but not IgG. In multivariate logistic regression analysis, independent risk factors for CA were confirmed with age and triglycerides (TG) in men and age, systolic blood pressure, pack-years of smoking, and low-density lipoprotein cholesterol (LDL-C) in women, but not IgG and IgA in either sex. These results do not support C. pneumoniae infection as an important risk factor for CA in this Japanese population.

Adult↗

PubMed2002

Two V(H)5 family genes expressed by human peripheral B cells display differential mutational frequencies in the V(H) region.

The heavy chain variable segment gene (V(H))5 family, one of the seven immunoglobulin (Ig) V(H) families, contains two functional genes, VH251 and VH32. To investigate functional differences between these V(H)5 family genes, V(H) segments expressed by human peripheral B cells were sequenced and analyzed. One hundred fifty-three sequences with unique V(H)DJ(H) recombinations were obtained from 17 adults. The mutational frequency of VH32 derived sequences (6.4%) was higher than that of VH251 derived sequences (4.4%), resulting in a significant difference (P<0.01). Significant differences in mutational frequencies between VH251 and VH32 derived sequences were observed in CDRs and FRs. No significant differences were found in CDR3 length distribution, D segment usage, or J(H) segment usage between VH251 and VH32 derived sequences. These results suggest that mutational frequency is affected, in part, by V(H) gene structure. The difference may occur after recombinational events in B cell development.

Adult↗

PubMed2002

Hepatitis C virus (HCV) RNA level determined by second-generation branched-DNA probe assay as predictor of response to interferon treatment in patients with chronic HCV viremia.

Using first- and second-generation branched-DNA probe assays (1st- and 2nd-bDNA), we investigated the predictors of favorable clinical response to interferon (IFN) treatment in patients with chronic HCV viremia. A total of 122 patients (85 genotype lb and 37 genotype 2a) with chronic HCV viremia received 24-week IFN-alpha treatment. Patients with sustained clearance of serum HCV RNA by polymerase chain reaction at six months after IFN treatment were defined as having a sustained response (SR). HCV RNA level was determined by 1st- and 2nd-bDNA assays prior to treatment. Mean HCV RNA level by 1st-bDNA was significantly higher in genotype lb patients [5.4 x 10(6) HCV genome equivalent (Meq)/ ml] than in genotype 2a patients (0.9 Meq/ml) (P < 0.05). There was no significant difference between patients with these genotypes in the level by 2nd-bDNA (1b: 5.2 Meq/ml and 2a: 3.1 Meq/ml). SR was achieved by 43 (35.2%) of 122 patients. Mean HCV RNA levels by both the 1st- and 2nd-bDNA of SR patients (1.0 and 1.9 Meq/ml) were significantly lower than those of non-SR patients (5.3 and 6.0 Meq/ml) (both P < 0.05). The SR rate in genotype 2a patients (59.5%) was significant higher than in genotype lb patients (24.7%) (P < 0.05). Stepwise logistic regression analysis showed that HCV RNA level < or = 1.0 Meq/ml by 2nd-bDNA (odds ratio = 7.6, compared to level > 1.0 Meq/ml, P < 0.05) was a significant predictive cutoff for SR. Using 2nd-bDNA, a significantly higher rate of SR was found in genotype lb patients with level < or = 1.0 Meq/ml (57.6%) than in those with level > 1.0 Meq/ml (3.8%) (P < 0.05). The SR rate of genotype 2a patients with level >1.0 Meq/ml (68.6%) was somewhat higher than for those with level < or = 1.0 Meq/ml (52.4%). These findings suggested that, using 2nd-bDNA, a low HCV RNA level of < or = 1.0 Meq/ml was the most favorable marker of successful IFN treatment and that patients with genotype 2a, even those with level >1.0 Meq/ml, had a high rate of SR to IFN treatment.

Adult↗

PubMed2002

TT-virus infection in Japanese general population and in hemodialysis patients.

To determine TT virus (TTV) prevalence and the persistence of viremia, we prospectively did cross-sectional and longitudinal studies using by the polymerase chain reaction to test the successive sera of 150 Japanese hemodialysis patients and compared these with those of 166 residents of a rural Japanese area endemic for hepatitis C virus (HCV). TTV DNA positivity was significantly higher in 50 (30.1%) of the residents than in 25 (16.7%) of the patients in 1997 (P < 0.05). TTV DNA positively in the patients was not associated with HCV RNA positivity and also increased with the number of blood transfusions and decreased with the duration of hemodialysis, but not significantly. Longitudinal study from 1997 to 1999 showed that persistent TTV DNA positivity was found significantly more often in 35 (21.1%) of the residents than in 13 (8.6%) of the patients (P < 0.05), and that persistent TTV DNA negativity was found significantly more often in 103 (68.7%) of the patients than in 91 (54.8%) of the residents (P < 0.05). Of the 25 patients and 50 residents TTV DNA positive in 1997, TTV DNA was eliminated more often in 12 (48.0%) patients than in 15 (30.0%) residents over the three years, but the difference was not significant. The route of TTV transmission might differ from HCV in that it could be nonparenteral. TTV was less prevalent in hemodialysis patients than residents, and the virus was more often eliminated by hemodialysis patients than by residents during the three-year observation period, possibly because of the effect of the hemodialysis procedure.

Adult↗

PubMed2002

Characterization of monoclonal antibodies against GRIM-19, a novel IFN-beta and retinoic acid-activated regulator of cell death.

A combination of interferon-beta (IFN-beta) and all-trans retinoic acid (IFN/RA) induces tumor cell apoptosis via some unknown mechanisms. Apoptosis is a gene-directed process that limits the proliferation of undesired cells. Several genes are required to regulate cell death in the higher-order animals. Earlier, we employed a gene expression knockout technique to isolate cell death-related genes. A novel gene, the gene associated with retinoid-interferon-induced mortality-19 (GRIM-19), was found to be essential for tumor cell death induced by IFN/RA. Here, we describe the development and characterization of three monoclonal antibodies (mAbs) against GRIM-19. GRIM-19 is present in the nucleus and cytoplasm. Its expression is induced by the IFN/RA combination. We also show that GRIM-19 inhibits the cell-transforming property of viral oncogenic protein viral IFN regulatory factor-1 (vIRF-1) via a physical interaction. mAbs developed in this study should be useful for studying the other physiologic roles of GRIM-19 and serve as a potent tool for studying tumor responses to IFN/RA therapy.

3T3 Cells↗

PubMed2002

The efficacy of herbal medicine (kampo) in reducing the adverse effects of IFN-beta in chronic hepatitis C.

The purpose of this study was to determine if the adverse effects of interferon (IFN) in hepatitis C patients could be reduced by treatment with Japanese Oriental (Kampo) medicine. Twelve patients with chronic hepatitis C were treated with a combination of IFN-beta and either Mao-to or Dai-seiryu-to (groups A and B), and 16 patients were treated with IFN-beta alone (group C). Mao-to was administered to eight patients and Dai-seiryu-to was administered to four in groups A and B, respectively. Adverse effects were evaluated by clinical and laboratory examinations. The severity of symptoms was daily self-classified into four categories (1: none, 2: very slight, 3: moderate, and 4: serious), using a questionnaire consisting of 29 items. Scores of symptom such as discomfort and fever in group A, and discomfort, general malaise, paresthesia and arthralgia in group B were significantly lower than those in group C (p < 0.05). In all patients, HCV-RNA was negative at the end of the treatment, and serum alanine aminotransferase (ALT) levels had normalized transiently in all group A and B patients with genotype 1b by 2 weeks after cessation of IFN treatment. This study indicates that Kampo medicines are useful for reducing the adverse effects accompanying IFN treatment in patients with chronic hepatitis C without reducing the antiviral effects.

Adult↗

PubMed2002

Inferior mesenteric arteriovenous fistula eight years after sigmoidectomy.

We report a 69-year-old woman with liver cirrhosis due to chronic hepatitis C virus (HCV) infection in whom iatrogenic arteriovenous fistula (AVF) developed after sigmoidectomy. A soft mass with bruit led to the diagnosis of inferior mesenteric AVF. Most mesenteric AVF cases have portal hypertension, but this patients showed none of the usual symptoms of portal hypertension; however, she had a splenomegaly that became worse after sigmoidectomy. Clinicians should be aware of the possibility of AVF in patients with a history of abdominal surgery.

Aged↗

PubMed2002

Molecular epidemiology of human T lymphotropic virus type 1 transmission in Okinawa, Japan.

To clarify the route of human T lymphotropic virus type 1 (HTLV-1) transmission, we sequenced three proviral genome regions (gag, env, int) of HTLV-1 from 18 carriers in 7 families in Okinawa, Japan and compared the strains with isolates from other countries. The nucleotide substitution frequency among sequences derived from a single carrier was low; 0-0.24% in gag, 0-0.54% in env, and 0-0.34% in int. All sequences showed the closest identity to the Cosmopolitan strain, with differences of only 0-1.91%. All 8 mother/child pairs had identical nucleotide sequences. Of 3 pairs of spouses, 2 had identical sequences, with transmission probably from husband to wife. The mothers of both wives were HTLV-1-negative. The HTLV-1 sequence of the other wife showed three nucleotide differences from the sequence of her husband, but was identical to the sequence of her mother. These results support previous seroepidemiological studies that HTLV-1 transmission occurs from mother to children and also between spouses.

Adolescent↗

PubMed2002

Clinical outcomes of hepatitis B virus (HBV) genotypes B and C in Japanese patients with chronic HBV infection.

The aims of this retrospective survey were to determine the epidemiologic distribution of hepatitis B virus (HBV) genotypes and analyze the genotype-related clinical differences among Japanese patients with chronic HBV infection. The 158 surveyed patients with chronic HBV infection lived in Fukuoka and Okinawa were serially tested for serum alanine aminotransferase (ALT) and hepatitis B e antigen (HBeAg). Follow-up was for a period of 10.8 +/- 6.4 years (mean +/- SD). The HBV genotypes were determined in sera by an enzyme-linked immunosorbent assay and detection of HBV DNA in serum was done by the transcription-mediated amplification-hybridization protection assay. Genotypes B and C were found in 58 (36.7%) and 100 (63.3%) of the patients, respectively. Genotype B was predominant in Okinawa (B = 86.9%, C = 13.1%), whereas genotype C was predominant in Fukuoka (B = 5.2%, C = 94.8%). The HBeAg positivity and ALT abnormality rates at the start of the observation period were significantly higher in patients with genotype C (66.0% and 84.0%) than in patients with genotype B (34.5% and 22.4%) (P < 0.05, respectively). The annual rate of spontaneous HBeAg disappearance in patients with genotype B was much higher than in patients with genotype C (8.38% versus 2.34%, respectively). Patients with genotype C who were continuously HBeAg negative from entry had a significantly higher ALT abnormality (58.8%) than those with genotype B (19.2%) (P < 0.05). Interestingly, patients with genotype C who became HBeAg negative after treatment with interferon had a high ALT abnormality (58.8%). All patients with an ALT abnormality were positive for HBV DNA in their serum. These findings indicate that patients with HBV genotype C have more severe liver deterioration because of the delay of HBeAg disappearance and continued HBV replication after HBeAg disappearance.

Adult↗

PubMed2002

Prevalence of antibody to Chlamydia pneumoniae in residents of Japan, the Solomon Islands, and Nepal.

Sera of 4,050 residents from Japan, 276 from the Solomon Islands, and 602 from Nepal were tested by an enzyme-linked immunosorbent assay to determine the prevalence of antibody to Chlamydia pneumoniae. The prevalence of IgG and IgA antibodies was significantly higher in the Solomon Islands (64.9% and 82.2%) and Nepal (73.1%, and 69.8%) than in Japan (53.6% and 41.1%). These prevalence rates increased throughout the teenage years in the Solomon Islands and Japan and leveled off with age, whereas in Nepal the prevalence rates gradually increased with age. The prevalence of a high (> 3.0) IgA antibody index, which is suggestive of acute infection, was significantly higher in the Solomon Islands (34.8%) than in Japan (3.2%) and Nepal (10.5%). The prevalence of IgG antibody ranged from 46.4% to 67.7%, and the prevalence of IgA antibody ranged from 33.7% to 61.8% in the four difference areas of Japan. These findings indicate considerable differences in the prevalence of antibodies to C. pneumoniae by age in these nations and between the regions of Japan tested.

Adolescent↗

PubMed2002

[A case of amyopathic dermatomyositis with systemic sclerosis sine scleroderma presenting abnormal vermiculation].

A 24-year-old Japanese woman was admitted to our hospital in January 2000 with daily diarrhea, abdominal distention, and abdominal pain. Raynaud's phenomenon with erythroderma desquamativum eruptions had been found in 1992. In 1999, small intestinal transillumination showed dilation of the second and third portion of the duodenum. She was diagnosed as amyopathic dermatomyositis because of Gottron's sign despite not having symptoms of myositis, normal serum CPK levels and no histological abnormality by muscle biopsy. In addition, the patient was diagnosed as systemic sclerosis sine scleroderma because Raynaud's phenomenon, leukoma and gastrointestinal dilation were present. Also, antinuclear antibody and anti centromere antibody were positive and anti Scl-70 antibody was dull-positive, despite the absence of scleroderma, extreme edema, and bone resorption. Careful, long term observation will be required because of the splanchnopathy in youth and the complications of systemic sclerosis.

Adult↗

PubMed2002

A Japanese case of severe refractory adult Still's disease: serum interleukin-18 is a possible marker of the response to low-dose cyclosporin A therapy.

A 22-year-old man was admitted to our hospital with a high fever, fatigue, mild arthritis, and bilateral pleural effusions. Laboratory tests revealed a high ESR, leukocytosis, high serum C-reactive protein level, and high serum ferritin level. Various antibiotics had been given by a local hospital with no response. He was diagnosed as having severe refractory adult Still's disease and was subsequently treated with high-dose steroid therapy and low-dose cyclosporin A. The serum interleukin-18 level was monitored throughout treatment and was found to be a potentially useful marker of disease activity as well as of the response to cyclosporin A therapy.

Adult↗

PubMedDate not supplied

Lead validation and SAR development via chemical similarity searching; application to compounds targeting the pY+3 site of the SH2 domain of p56lck.

Compound selection based on chemical similarity has been used to validate active "parent" compounds identified via database searching as viable lead compounds and to obtain initial structure-activity relationships for those leads. Twelve parent compounds that have inhibitory activity against the SH2 domain of the p56 T-cell tyrosine kinase (Lck) are the focus of this study. Lck is involved in the T-cell mediated immune response, and inhibitors of Lck protein-protein interactions could potentially be used to develop novel immunosuppressants. Similarity searches for each parent compound were performed using 2D structural fingerprints on a database containing 1,300,000 commercially available compounds. The inhibitory activity of the selected compounds was assessed using enzyme immunoassay (EIA). In general, the most active parent compounds yield the most high activity similar compounds; however, in two cases low activity parent compounds (i.e. inhibitory activity < 25% at 100 microM) yielded multiple similar compounds with activities > 60%. Such compounds may, therefore, be considered as viable lead compounds for optimization. Structure-activity relationships were explored by examining both ligand structures and their computed bound conformations to the protein. Functional groups common to the active compounds as well as key amino acid residues that form hydrogen bonds with the active compounds were identified. This information will act as the basis for the rational optimization of the lead compounds.

Computer Simulation↗

PubMedDate not supplied

Incidence of atopic dermatitis in nursery school children - a follow-up study from 2001 to 2004, Kyushu University Ishigaki Atopic Dermatitis Study (KIDS).

Atopic dermatitis (AD) is a multifactorial disease that usually decreases the quality of life of affected patients. We monitored the incidence of AD and serum total IgE levels annually among nursery school children in Ishigaki Island, Okinawa, Japan, from 2001 to 2004. A total of 1731 children were enrolled. The prevalence of AD ranged from 3.7 to 11% in each year, with no significant difference between boys and girls. 869 children were examined at least twice. 71.6% (53/74) of AD patients regressed spontaneously, whereas 5.5% (44/795) of non-AD individuals developed AD during the 3-year follow-up. Increases in total IgE levels were greater and more rapid in children with long-term AD than in those who had spontaneously regressed, had newly-developed AD or did not have AD. The regression rate of AD was > 70% while new-onset AD occurred at a rate of 3.67%/person year in nursery school children of Ishigaki Island.

Child, Preschool↗