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Biomedical subjects

R Fukuda

Publications and source records attributed to R Fukuda.

At least 91 records · Page 5Linked to original sources
PubMed1996

Clinical significance of LEA-1 expression in adult acute myeloid leukemia.

In this study, we examined expressions of several adhesion molecules (AdMs), i.e. leukocyte function antigen-1 (LFA-1: CD11a/CD18), Hermes homing receptor (CD44) and intercellular adhesion molecule-1 (ICAM-1: CD54), on leukemia cells from 51 adult patients with newly diagnosed acute myeloid leukemias (AMLs) to elucidate clinical significance of these AdM expressions. Those expressions in lymphoid malignancies have been correlated with tumor evolutions, but CD44 was detected in all the AML cases examined and CD54 expression did not associate with their clinical characteristics or outcomes. However, we found that LFA-1 expressions significantly correlated with splenomegaly, resistance to induction chemotherapies and short survival periods in AML patients.

Acute Disease↗
PubMed1996

Hepatitis B virus with X gene mutation is associated with the majority of serologically "silent" non-b, non-c chronic hepatitis.

Hepatitis B virus (HBV) with X gene mutations has been a putative pathogen of chronic hepatitis without serological markers of known hepatitis viruses. The aim of this study was to reconfirm whether the HBV with the X gene mutation is associated with these serologically "silent" non-B, non-C (NBNC) chronic hepatitis, alcoholic liver disease (ALD) and autoimmune hepatitis (AIH). HBV DNA was amplified from serum and sequenced in 30 patients with NBNC chronic hepatitis in comparison with 20 patients with ALD and 5 patients with AIH. HBV DNA was identified in 21 patients (70%) in NBNC chronic hepatitis by nested polymerase chain reaction while only one patient (5%) in ALD and none in AIH showed HBV DNA. Eighteen (85.7%) of the 21 identified HBV DNAs had an identical 8-nucleotide deletion mutation at the distal part of the X region. This mutation affected the core promoter and the enhancer II sequence of HBV DNA and created a translational stop codon which truncated the X protein by 20 amino acids from the C-terminal end. All the HBV DNAs had a precore mutation at the 83rd nucleotide resulting in disruption of HBe antigen synthesis. These results indicate that HBV mutants are closely associated with the majority of serologically "silent" NBNC chronic hepatitis cases and the population of such mutant HBV DNAs is not uniform.

Adult↗
PubMed1996

Relationship between the intrahepatic expression of interferon-alpha receptor mRNA and the histological progress of hepatitis C virus-associated chronic liver diseases.

Histological progress is one of the predictors of an unfavourable response to interferon (IFN) therapy in hepatitis C virus (HCV)-associated chronic liver diseases (CLD). The aim of the present study was to investigate whether histological progress has an association with the expression of IFN receptor (IFN-Rc) in the liver. Expression of mRNA of the IFN-Rc for IFN-alpha was investigated by reverse transcription polymerase chain reaction using liver biopsy specimens from 37 HCV-associated CLD comprising 11 liver cirrhosis (LC) and 26 chronic hepatitis (CH) cases. IFN-alpha and IFN-beta mRNA were detected in over 90% of subjects. In contrast, the detection rate of IFN-Rc mRNA in chronic persistent hepatitis, chronic hepatitis 2A, chronic hepatitis 2B and liver cirrhosis (LC) was 100, 71.4, 22.2 and 0%, respectively. The absence of IFN-Rc mRNA was significantly associated with the severity of fibrosis of the liver. These results indicated that IFN-Rc expression decreases with the histological progress of the disease, suggesting that lower expression of IFN-Rc mRNA may be partially responsible for the poor IFN response in LC.

Adult↗
PubMed1996

Intrahepatic expression of pro-inflammatory cytokine mRNAs and interferon efficacy in chronic hepatitis C.

To investigate the relationship between intrahepatic cytokine expression and interferon (IFN) response in chronic hepatitis C [CH(C)], interleukin (IL)-1 beta, -2, -4, -6, -8, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta mRNAs were investigated semiquantitatively by reverse transcription polymerase chain reaction using serial liver biopsies taken before and after IFN-alpha treatment from 24 patients with CH(C), including 12 responders and 12 non-responders. Before IFN treatment, IL-2, TNF-beta, IFN-gamma and IL-8 mRNA were associated with severe hepatitis activity whereas IL-4 mRNA was associated with weak hepatitis activity, regardless of IFN response. IL-2, TNF-beta and IFN-gamma mRNAs were significantly greater in IFN non-responders. After IFN treatment a complete response to IFN was significantly associated with the disappearance of these pro-inflammatory cytokines, whereas non-responders retained the expression of cytokine mRNA as before IFN treatment. Our results indicated that IFN-alpha treatment may modulate the intrahepatic cytokine network, and this may be one mechanism of IFN-alpha that reduces hepatitis activity, aside from an anti-viral effect. A difference in cytokine network may be involved in IFN response in CH(C).

Adult↗
PubMed1996

[Comparison of free non-tryptophan fluorescent substances in water-soluble fraction of brunescent and non-brunescent human cataract].

We compared the concentrations of protein-unbound non-tryptophan fluorescent substances in the water-soluble fraction between non-brunescent (NBr) and brunescent (Br) human cataractous lens nuclei. Lens nuclei (NBr, 22 eyes: Br, 9 eyes) from non-diabetic patients, obtained by extracapsular cataract extraction, were individually homogenized and centrifuged. The supernatants were subsequently ultra-dialyzed and assessed by high pressure liquid chromatography. 3-Hydroxykynurenine-O-beta-glucoside (3-HKG) as well as an unidentified fluorescent substance was detected. While the concentrations of the former substance did not significantly differ between the NBr and the Br nuclei (NBr, 0.55 +/- 0.49 mumol/g wet weight: Br, 0.90 +/- 0.64 mumol/g wet weight; p > 0.1), the concentration of the latter substance was significantly greater in the Br nuclei than in the NBr nuclei (NBr, 2.2 x 10(3) +/- 5.4 x 10(3) AU/g wet weight: Br, 1.4 x 10(5) +/- 1.1 x 10(5) AU/g wet weight; AU: area unit, p < 0.01). An incubation of the dialysate with beta-glucosidase eliminated the peak corresponding to the latter substance. These results suggest that an unidentified protein-unbound fluorescent substance, which is presumably a beta-glucoside, in the lens nuclei is related to the coloration of human lens nuclei.

Cataract↗
PubMed1996

Modulation of peripheral blood lymphocyte subsets during methylprednisolone pulse therapy.

We determined fluctuations in circulating lymphocyte subsets induced by methylprednisolone pulse therapy (MPT) and the continuous administration of prednisolone (PSL) in 17 patients with autoimmune or systemic rheumatic disease. Two-color flow cytometry, using monoclonal antibodies to various lymphocyte subsets, was performed to identify a possible association between the clinical efficacy of treatment and modulative effects on each subset. Both MPT and continuous oral PSL showed suppressive effects on most of the lymphocyte subsets: CD4+, CD45RA or CD45RA+CD4+, CD8+, CD11b.CD8+, CD5+ B, and CD57+ or CD57 CD16+ cells. Modulation of lymphocyte subsets were more profound with MPT than with continuous oral PSL. The results are relevant to the different degrees of immuno-suppression effected by the two treatment modalities. We found that the number of CD45RA.CD4+ cells after MPT treatment correlated with the clinical efficacy of the treatment: the less CD45RA.CD4+ cell numbers decreased after MPT treatment, the greater was the clinical efficacy of the treatment. The results probably are associated with a rapid recovery of the subset after MPT treatment in the responders. Thus, the sequential monitoring of circulating lymphocyte subsets is useful in predicting the clinical effects of MPT treatment.

Adult↗
PubMed1995

Activation of the apoptotic Fas antigen-encoding gene upon influenza virus infection involving spontaneously produced beta-interferon.

We previously demonstrated that influenza virus infection induces apoptosis in culture cells. Here, we examined the activation of the Fas antigen gene that encodes an apoptosis-mediating membrane protein in the virus-infected cells. The virus elicited a transient but marked increase in Fas antigen mRNA 3 to 4 hr after infection, followed by the expression of the antigen on the cell surface. Poly(I)-poly(C), a synthetic double-stranded RNA, similarly activated Fas antigen gene expression, and poly(I)-poly(C)-treated cells are highly susceptible to the cell killing effect of IgM isotype of anti-Fas monoclonal antibody. On the other hand, the IgG isotype of anti-Fas monoclonal antibody, which has an inhibitory effect on Fas Ag-mediated cell death, suppressed the virus-induced cell death. Prior exposure of the cells to anti-interferon-beta antibody decreased the degree of cell death as well as the amount of Fas mRNA. The autophosphorylation activity of double-stranded RNA-activated protein kinase was also decreased in the antibody-treated cells. Moreover, a protein kinase inhibitor, 2-aminopurine, blocked the Fas Ag gene activation by poly(I)-poly(C). These results suggested that the activation of Fas Ag gene in the early phase of infection is an important event for apoptosis, and that it is regulated by the double-stranded RNA/interferon system involving protein phosphorylation.

2-Aminopurine↗
PubMed1995

No evidence of linkage or association between tyrosine hydroxylase gene and affective disorder.

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of dopamine and norepinephrine, and therefore is of significant interest as a candidate gene in studies of affective disorders. We have carried out the linkage study between the susceptibility gene for affective disorder and tetranucleotide polymorphism of TH gene in five Japanese pedigrees. In addition to the linkage approach, we have undertaken an allelic association study using 74 patients with affective disorder and 78 controls with polymorphisms at the TH gene and the nearby dopamine D4 receptor gene. No evidence for linkage or associations were found. These results indicate that TH gene is less likely to contribute to the genetic component of affective disorders.

Adolescent↗
PubMed1995

Expression rate of cytokine mRNA in the liver of chronic hepatitis C: comparison with chronic hepatitis B.

This study was carried out to test the hypothesis that, in chronic hepatitis (CH), inflammatory processes, including viral replication, host immune response, and hepatocyte destruction, are regulated by a cytokine network in the liver. Expression of the mRNA of the cytokines IL1-beta, IL2, IL4, IL5, IL6, TNF-alpha, and IFN-gamma, the lymphocyte markers CD4 and CD8, and the HLA class I molecule, beta 2-microglobulin (B2MG) in the liver tissue of 20 CH(C) cases and 9 CH(B) patients was investigated by the reverse transcription polymerase chain reaction (RT-PCR) method. TNF-alpha, CD4, and B2MG mRNA were detected in 100% of cases of in both CH(B) and CH(C). The expression rates of IL1-beta, IL2, IL4, IFN-gamma, and CD8 mRNA were 80%, 40%, 25%, 40%, and 80% in CH(C) and 88.9%, 44.5%, 30%, 55.6%, and 100% in CH(B). IL6 mRNA was detected only in CH(B), in 22.2% of cases, IL5 mRNA was not detected in either CH(B) or CH(C). IL2, IL4, and IFN-gamma mRNA were expressed significantly more frequently in patients who had high serum ALT and a high histological activity index (HAI) score. There was no difference in cytokine expression between CH(B) and CH(C), except in IL6, suggesting the existence of a common immunopathogenesis for CH(B) and CH(C). In chronic viral hepatitis, IL1-beta and TNF-alpha appear to play a major role in immune responses and IL2, IL4, and IFN-gamma seem to be associated with increased cytotoxic T cell response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

dinP, a new gene in Escherichia coli, whose product shows similarities to UmuC and its homologues.

A new gene, designated dinP, was found during E. coli genomic sequencing around the 5.5 min region. Its coding region is preceded by a sequence similar to the consensus binding sequence for LexA, the so-called SOS box sequence. The amino acid sequence of DinP (351 amino acid residues) has a strong similarity to the C. elegans hypothetical protein F22B7.6 and weaker similarities to the UmuC homologues in E. coli and Salmonella typhimurium and also to REV1 of Saccharomyces cerevisiae. Another SOS operon (dinJ1 and dinJ2 genes) found in this region is also described.

Amino Acid Sequence↗
PubMed1995

X gene and precore region mutations in the hepatitis B virus genome in persons positive for antibody to hepatitis B e antigen: comparison between asymptomatic "healthy" carriers and patients with severe chronic active hepatitis.

Hepatitis B virus (HBV) carriers with antibody to hepatitis e antigen comprise asymptomatic carriers (ASCs), who have low replication levels of HBV, and patients with chronic active hepatitis (CAH), who have high levels of viral replication. To investigate whether defects in the X protein might be responsible for this difference in the level of viral replication, nucleotide sequences of X and precore gene regions in serum HBV were analyzed in 19 ASCs and 9 CAH patients. All patients had a point mutation creating a stop codon in the precore region. Seventeen ASCs (87.3%) had identical mutations consisting of 4 noncontiguous 1-bp deletions or an 8-bp deletion, both of which truncate the normal X protein, whereas no CAH patient had an X gene mutation (P < .001). Thus, deletion of the X protein might be responsible for the low levels of viral replication in ASCs.

Adult↗
PubMed1995

Gene expression of perforin and granzyme A in the liver in chronic hepatitis C: comparison with peripheral blood mononuclear cells.

Perforin and granzyme A are the major effectors of cytotoxic T cells in cell-mediated cytotoxicity. However, there has been no report on these effectors in chronic viral hepatitis. In the present study, the expression of perforin and granzyme A mRNA was investigated by the reverse transcription polymerase chain reaction method using liver biopsy specimens and peripheral mononuclear cells (PBMC) from 21 patients with chronic hepatitis C and 5 control cases. Perforin mRNA was detected only in the liver of chronic hepatitis patients but not in the control livers. Conversely, perforin mRNA was not expressed in PBMC of the patients with chronic hepatitis (P < 0.01). Granzyme A mRNA was detected both in the liver and PBMC of all the cases including control cases. These results indicated that the perforin is an important effector molecule in the hepatocyte lysis in chronic viral hepatitis C.

Base Sequence↗
PubMed1995

The expression of IL-2, IL-4 and interferon-gamma (IFN-gamma) mRNA using liver biopsies at different phases of acute exacerbation of chronic hepatitis B.

To investigate the hypothesis that Th1 phenotype cytokines are associated with the increasing activity of hepatitis and Th2 phenotype cytokines with decreasing activity in the liver of chronic viral hepatitis, expressions of the mRNA of the cytokines IL-2, IFN-gamma and IL-4 in the liver of 23 patients with chronic hepatitis B were investigated by reverse transcription polymerase chain reaction. Patients were divided into three groups according to the phase of acute exacerbation of hepatitis as increasing (n = 9), decreasing (n = 8), and stable phase (n = 6). Both IL-2 and IFN-gamma mRNA were preferentially expressed in increasing phase than in decreasing phase (P < 0.01, P < 0.05, respectively) and associated with the high serum alanine aminotransferase (ALT) level. On the other hand, IL-4 mRNA was detected in decreasing phase with significant frequency compared with increasing phase (P < 0.05). However, expression of IL-4 mRNA was not associated with serum ALT level. Our results suggest that Th1 phenotype cytokines up-regulate and Th2 phenotype cytokines down-regulate the liver inflammation of chronic viral hepatitis.

Adolescent↗
PubMed1995

[Clinical and pathological features of Sjögren's syndrome associated with autoimmune thyroid diseases].

Sjögren's syndrome (SS) is a chronic inflammatory disease of the exocrine glands accompanied by mononuclear cell infiltration. The histopathological features of the salivary and lacrimal glands of SS resemble those of the thyroid glands of autoimmune thyroiditis (chronic thyroiditis; CT). In addition, both SS and CT frequently recognized in the patients with other organ-specific or systemic autoimmune diseases (collagen-vascular diseases; CVD). We analyzed the incidences of CT among patients with SS or CVD, and compared clinical, immunological and endocrinological profiles between the SS patients with and those without CT. CT was the most frequent organ-specific auto-immune disease recognized in both primary and secondary SS patients. The thyroid disease similarly associated with CVD patients, regardless of the presence of SS. Several studies have also suggested that subclinical diseases are frequent in both CT and SS patients. The clinical and immunohematological features were almost identical between SS patients with and those without CT. Furthermore, the clinical, serological and endocrinological profiles of thyroid disease were very similar between SS patients with CT and CT patients without SS. These results indicate that CT and SS are independent autoimmune diseases, and the thyroid involvement observed in patients with primary or secondary SS is not an extraglandular manifestation of SS.

Chronic Disease↗