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Biomedical subjects

M Yamazaki

Publications and source records attributed to M Yamazaki.

At least 307 records · Page 17Linked to original sources

Allelic variants of the human MHC class I chain-related B gene (MICB).

The human major histocompatibility complex (MHC) is located within a 4 megabase segment on chromosome 6p21.3. Recently, a highly divergent MHC class I chain-related gene family, MIC was identified within the class I region. The MICA and MICB genes in this family have unique patterns of tissue expression. The MICA gene is highly polymorphic, with more than 20 alleles identified to date. To elucidate the extent of MICB allelic variations, we sequenced exons 2 (alpha 1), 3 (alpha 2), 4 (alpha 3), and 5 (transmembrane) as well as introns 2 and 4 of this gene in 46 HLA homozygous B-cell lines. We report the identification of eleven alleles based on seven non-synonymous, two synonymous, and four intronic nucleotide variations. Interestingly, one allele has a nonsense mutation resulting in a premature termination codon in the alpha 2 domain. Thus, MICB appears to have fewer alleles than MICA, not unlike the allelic ratio between the HLA-C and -B loci. A preliminary linkage analysis of the MICB alleles with those of the closely located MICA and HLA-B genes revealed no conspicuous linkage disequilibrium between them, implying the presence of a potential recombination hotspot between the MICB and MICA genes.

Alleles↗

Detection of the soluble form of the Fas molecule in patients with multiple sclerosis and human T-lymphotropic virus type I-associated myelopathy.

We evaluated the presence of soluble Fas molecule (sFas) in the cerebrospinal fluids (CSF) and the sera of patients with multiple sclerosis (MS) or human T-lymphotropic virus type I (HTLV-I) associated myelopathy (HAM) using an enzyme-linked immunosorbent assay (ELISA). Patients with multiple sclerosis in the active phase had higher sFas serum levels than control (p < 0.005). In addition, significantly increased serum levels of sFas were found in patients with HAM (p < 0.005). We found a significantly increased CSF levels of sFas in patients with HAM and patients with MS in the active stage (p < 0.005). These results suggest that serum sFas may be related to clinical activity in patients with MS and that Fas may play an important role in the pathogenesis of HAM.

Adult↗

Phosphatidylserine suppresses Theiler's murine encephalomyelitis virus-induced demyelinating disease.

Intracerebral inoculation of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelinating disease. Various cytokines may play an important role in the pathogenesis of this disease. Tumor necrosis factor (TNF)-alpha contributes to the further development of perivascular cellular infiltration and demyelination in the central nervous system (CNS). Phosphatidylserine (PS), a major anionic phospholipid of mammalian cells, has been proposed to function as a regulator of immune and inflammatory responses, especially reducing TNF-alpha production and release in mice. We studied the effect of PS on TMEV-induced demyelinating disease (TMEV-IDD). We injected TMEV intracerebrally into susceptible SJL/J mice and induced TMEV-IDD. PS were injected intraperitonealy, and clinical course and various immunological indicators were closely studied. The results show that when PS were administered in the effector phase. TMEV-IDD was significantly (P < 0.01) suppressed both clinically and histologically. In an ELISPOT assay, the number of TNF-alpha producing spleen cells was low in PS treated mice compared with saline treated control mice. mRNA of TNF-alpha was not detected in spleen cells of mice PS treated in the effector phase. These data suggest that administration of PS suppresses TMEV-IDD by suppressing TNF-alpha production in the effector phase.

Animals↗

Fibrin deposition in the central nervous system correlates with the degree of Theiler's murine encephalomyelitis virus-induced demyelinating disease.

We examined the role of coagulation-fibrinolysis system in Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). The degree of fibrin deposition around the vessels in the spinal cord was significantly higher in susceptible SJL/J mice on 30 days post intracerebral injection (i.c.) than resistant C57BL/6 mice on 30 days post i.c. or mock infected SJL/J mice. Treatment with batroxobin (30 BU/kg/day), which is a thrombin-like defibrinogenating enzyme, causing a profound degree of afibrinogenemia, suppressed clinical signs of TMEV-IDD. Plasma fibrinogen concentration was significantly decreased in batroxobin-treated mice. Histologically, though the degree of perivascular mononuclear cell infiltration in the spinal cord was not suppressed in batroxobin-treated mice compared to saline-treated control mice, fibrin deposition was markedly suppressed in batroxobin-treated mice. These findings suggest that batroxobin suppresses TMEV-IDD through its defibrination effect, and provide evidence that CNS-associated deposition of fibrin and ensuing fibrinolysis, together with increased permeability of the blood-brain barrier (BBB), are prerequisite events for clinical manifestations of TMEV-IDD.

Animals↗

Basaloid squamous carcinoma of the larynx: report of a case.

Basaloid squamous carcinoma (BSC) is a rare neoplasm. We present a case of basaloid squamous carcinoma of the larynx in a 57-year-old male patient. The diagnosis before treatment was supraglottic carcinoma (T3N1MO) and biopsy of the larynx revealed a poorly differentiated squamous cell carcinoma. Total laryngectomy and right radical neck dissection were performed, and pathological studies of a specimen removed from the larynx revealed BSC of the larynx. The patient's postoperative progress was uneventful, however, 12 months later he developed lung metastasis of the left side. The patient underwent partial resection of the lung. He developed recurrence of lung metastasis 6 months later. Chemotherapy with cisplatin (CDDP) and vindesine sulfate (VSD) was administered in two courses, but the efficacy was evaluated as no change (NC). At present, 26 months after the first visit, he has been asymptomatic with lung metastasis, and there was no evidence of recurrence in the neck.

Carcinoma, Basosquamous↗

Cloning and molecular analysis of structural genes involved in anthocyanin biosynthesis and expressed in a forma-specific manner in Perilla frutescens.

Two cultivars of Perilla frutescens, red and green formas are known to differ in anthocyanin accumulation in leaves and stems. cDNA clones encoding the enzymes involved in anthocyanin biosynthesis, chalcone synthase (CHS), flavanone 3-hydroxylase (F3H), dihydroflavonol 4-reductase (DFR), and UDP glucose: flavonoid 3-O-glucosyltransferase (3GT), were isolated from cDNA libraries derived from the leaves of a red forma of P. frutescens by screening with partial fragments amplified by means of polymerase chain reaction (PCR) and heterologous cDNAs as probes. The deduced amino acid sequences of these four genes exhibited 40-90% identity with those reported for the corresponding gene from other unrelated species. Southern blot analysis for these genes and two other structural genes, the leucoanthocyanidin dioxygenase (LDOX, anthocyanidin synthase) and anthocyanin acyltransferase (AAT) genes, indicated that each gene comprises a small multi-gene family. More than three copies of the CHS gene are present, two copies of the other genes being present. The expression of five genes, the exception being the CHS gene, was detected only in red leaves of the red forma of P. frutescens, i.e. not in green leaves of the green forma plant. The CHS gene was expressed in both red and green leaves, but 10-fold more in red leaves than in green leaves. These results suggest that the expression of all structural genes examined is coordinately regulated in a forma-specific manner. Under weak-light conditions, the accumulation of both anthocyanin and mRNAs of biosynthetic enzymes was lower in leaves of the red forma. High-intensity white light coordinately induced the accumulation of transcripts of all six genes examined in the mature leaves of red P. frutescens.

Acyltransferases↗

Production of xanthan gum by Sphingomonas bacteria carrying genes from Xanthomonas campestris.

Twelve genes coding for assembly, acetylation, pyruvylation, polymerization, and secretion of the polysaccharide xanthan gum are clustered together on the chromosome of the bacterium Xanthomonas campestris. These genes (gumBCDEFGHIJKLM) are sufficient for synthesis of xanthan gum when placed in bacteria from a different genus, Sphingomonas. The polysaccharide from the recombinant microorganism is largely indistinguishable, structurally and functionally, from native xanthan gum. These results demonstrate that a complex pathway for biosynthesis of a specific polysaccharide can be acquired by a single inter-generic transfer of genes between bacteria. This suggests the biological and commercial feasibility of synthesizing xanthan gum or other polysaccharides in non-native hosts.

DNA, Recombinant↗

Alterations of platelet, coagulation, and fibrinolysis markers in patients with acute ischemic stroke.

Alterations of platelet, coagulation, and fibrinolysis markers were investigated to determine the indications for antithrombotic therapy in patients with different clinical categories of acute cerebral infarction. Marked platelet activation was observed in platelet function tests, including measurements of platelet-specific proteins and platelet survival, platelet scintigraphy in the brain, and platelet fibrinogen binding assay, in patients with atherothrombotic stroke. Among patients with atherothrombotic stroke, increases of thrombin-antithrombin III complex (TAT) and D-dimer were frequent in addition to the findings of platelet activation in patients showing progressing stroke. Patients with cardioembolic stroke demonstrated marked elevation of coagulation markers, TAT and fibrinopeptide A, and fibrinolysis markers, D-dimer and plasmin-alpha2-plasmin inhibitor complex, as well as platelet activation. In contrast, neither activation was seen in patients with lacunar stroke. On the basis of these findings, antiplatelet therapy is indicated for stable or improving stroke, whereas anticoagulant therapy is indicated for progressing stroke among patients with atherothrombotic stroke. In patients with cardioembolic stroke, anticoagulant therapy should be started as soon as possible, or should be followed by thrombolytic therapy in the hyperacute phase. However, further investigation appears necessary for recommendations for patients with lacunar stroke.

Acute Disease↗

Anti-adhesion molecule therapy in Theiler's murine encephalomyelitis virus-induced demyelinating disease.

We examined the role of leukocyte function-associated antigen (LFA)-1 and its counter-receptor intercellular adhesion molecule (ICAM)-1, one of the most important pairs of adhesion molecules, in the development of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Immunohistochemical study showed hyper-expression of ICAM-1 on vascular endothelial cells and expression of LFA-1 on mononuclear infiltrating cells in the spinal cords of TMEV-infected mice. Treatment with mAb to ICAM-1 and/or LFA-1 molecules resulted in significant suppression of the development of demyelinating disease, both clinically and histologically, with down-regulation in the CNS of the respective adhesion molecules after treatment. In mice treated with these mAb, the specific delayed-type hypersensitivity and T cell proliferative responses for TMEV were decreased. The production of tumor necrosis factor-alpha and IFN-gamma in spleen cells was also decreased, but IL-4 production remained unchanged. These data suggest that ICAM-1/LFA-1 interaction is critically involved in the pathogenesis of TMEV-IDD and that antibodies to these adhesion molecules could be a novel therapeutic approach to the treatment of demyelinating diseases such as human multiple sclerosis.

Animals↗

Consumption of buckwheat protein lowers plasma cholesterol and raises fecal neutral sterols in cholesterol-Fed rats because of its low digestibility.

Buckwheat protein product (BWP) has a strong hypocholesterolemic activity in rats fed a cholesterol-enriched diet. In this study, we examined the influence of BWP on fecal excretion of sterols and nitrogen in rats fed a diet containing 5 g/kg cholesterol and 1.25 g/kg sodium cholate, and we examined whether the cholesterol-lowering activity of BWP is due to its low digestibility. In Experiment 1, rats fed BWP for 3 wk had significantly lower concentrations of plasma cholesterol and enhanced excretion of fecal total neutral sterols and nitrogen compared with rats fed casein. There was a significant correlation between fecal total neutral sterols and nitrogen (r = 0.89, P < 0.01). Fecal excretion of acidic sterols was unaffected by BWP. In Experiment 2, plasma cholesterol in rats fed trypsin-digested BWP for 2 wk was significantly higher than that in rats fed intact BWP. In Experiment 3, rats were fed BWP, low-molecular-weight fraction of the digest of BWP (LMF ) or high-molecular-weight fraction of the digest of BWP (HMF ) for 3 wk. Plasma cholesterol was lower in the BWP group than in the LMF group (P < 0.05), whereas that in the HMF group was intermediate. The in vitro digestibility of BWP with pepsin and pancreatin was significantly lower than that of casein. The results suggest that the cholesterol-lowering effect of BWP is mediated by higher fecal excretion of neutral sterols and that lower digestibility of BWP is at least partially responsible for the effect.

Animals↗

Induction of tumor necrosis factor in a murine tumor by systemic administration of a novel synthetic lipid A analogue, ONO-4007.

The effect of a novel synthetic lipid A analogue, ONO-4007, on tumor necrosis factor (TNF) production was investigated in normal and tumor-bearing mice. When vehicle was administered to normal mice, slight TNF activity was detected in some organs, but more TNF activity was detected in spleen, liver, lung, kidney, and serum when ONO-4007 (300 micrograms/mouse) was administered. When vehicle was given to tumor bearers, on the other hand, little TNF was detected in most organs, but when ONO-4007 was given, more TNF was produced in many organs, particularly spleen, liver, and tumor tissue. TNF production of spleen and liver reached a maximum 1-2 h after ONO-4007 injection and then decreased rapidly, but that of tumor remained high for at least 6 h after administration. When mice were pretreated with dexamethasone, TNF activity of normal organs were completely inhibited, but that of tumor was only partially decreased. We have shown that ONO-4007 causes rapid, definite growth inhibition of solid tumor, and speculate that long-sustained intratumoral TNF is the main cause of this beneficial anti-tumor effect. We report here that ONO-4007 can induce TNF in tumor locus, and its utilization may offer a new therapeutic method.

Animals↗

Identification of a novel HLA-B allele (B*4202) in a Saudi Arabian family with Behçet's disease.

A new HLA-B antigen, tentatively called HLA-B42AND, was identified as a B42 serologic variant in a Saudi Arabian family. DNA sequencing analysis of the second and third exon of this new B allele revealed that B42AND was identical to B*4201 except for a single T to C substitution at position 97 of exon 2. This substitution results in histidine (CAC) at codon 9 in B42AND instead of tyrosine (TAC) in B*4201. The antigen frequency of B42AND in a Saudi Arabian population was around 10%. This novel B42AND has officially been named HLA-B*4202.

Alleles↗

A novel method to evaluate thromboresistance of drip chambers with filter used in extracorporeal blood circuits for hemodialysis.

We have developed a novel method to simultaneously evaluate thromboresistance of two different types of drip chambers with a filter used in extracorporeal blood circuits for hemodialysis using canine arteriovenous shunt models. Bilateral bypasses between the femoral artery and vein on both sides of the animal were formed with 2 test circuits consisting of polyvinyl chloride tubing and two types of drip chambers with filters. Blood flow was derived into the drip chambers with a filter and returned to the femoral vein without using peristaltic pumps and systemic anticoagulants. By monitoring the quantitative changes of the blood flow rate through each drip chamber with a filter and measuring the time elapsed before the blood flow through its was completely obstructed by clots, thromboresistance of the drip chambers was evaluated under the same blood conditions. The drip chamber with a filter that had a small effective filter area, a big pore size, and slitlike pores showed better thromboresistance. This novel method proved useful in evaluating the thromboresistance of differently designed drip chambers with a filter.

Animals↗

eaeA genes in Escherichia coli derived from Japanese patients with sporadic diarrhea.

To investigate the prevalence of attaching and effacing Escherichia coli, we examined 364 strains isolated from the feces of 9,684 patients with diarrhea at the Anjo Kosei Hospital in Japan for the presence of eaeA. Twenty-nine (8%) of the strains were eaeA positive. Of enteropathogenic E. coli (EPEC), 11 of the 87 (13%) strains were for the positive eaeA gene. The serotypes and the numbers of eaeA-positive strains among the strains tested were as follows: O26:H-(2/3), O55:H7 (4/4), O55:H-(2/ 2) and O128:H2(3/3). Two enterohemorrhagic E. coli (EHEC) strains (Verotoxin positive O157:H7) were also eaeA positive. Among 260 non-EPEC strains that were not categorized as diarrheagenic E. coli, 16 (6%) were eaeA positive. Those serotypes were as follows: O15:H2, O20:H6, O28:H28, O63:H6. O153:H7, O28:H6, O153:H19 and O157:H45. EPEC strains including O18:H7 and six other serotypes, enteroinvasive E. coli (EIEC), and enterotoxigenic E. coli (ETEC) were all eaeA negative.

Adhesins, Bacterial↗

Novel detoxification of the trichothecene mycotoxin deoxynivalenol by a soil bacterium isolated by enrichment culture.

A mixed microbial culture capable of metabolizing deoxynivalenol was obtained from soil samples by an enrichment culture procedure. A bacterium (strain E3-39) isolated from the enrichment culture completely removed exogenously supplied deoxynivalenol from culture medium after incubation for 1 day. On the basis of morphological, physiological, and phylogenetic studies, strain E3-39 was classified as a bacterium belonging to the Agrobacterium-Rhizobium group. Thin-layer chromatographic analysis indicated the presence of one major and two minor metabolites of deoxynivalenol in ethyl acetate extracts of the E3-39 culture filtrates. The main metabolite was identified as 3-keto-4-deoxynivalenol by mass spectroscopy and 1H and 13C nuclear magnetic resonance analysis. The immunosuppressive toxicity of 3-keto-4-deoxynivalenol was evaluated by means of a bioassay based on the mitogen-induced and mitogen-free proliferations of mouse spleen lymphocytes. This compound exhibited a remarkably decreased (to less than one tenth) immunosuppressive toxicity relative to deoxynivalenol, indicating that the 3-OH group in deoxynivalenol is likely to be involved in exerting its immunosuppressive toxicity. Strain E3-39 was also capable of transforming 3-acetyldeoxynivalenol but not nivalenol and fusarenon-X.

Animals↗

Thiamine increases expression of yeast gene.

We found that CPY production in Saccharomyces cerevisiae KS58-2D/pCY303 was increased by the addition of thiamine into the medium, while the addition of thiamine had no effect on cell growth. It became clear that the positive effect of thiamine was due to transcriptional increase, because the levels of CPYmRNA were increased according to the amount of thiamine added. Furthermore, it was suggested that thiamine generally increases the expression of yeast genes, since the expression of the luciferase gene that was artificially constructed was also increased to some extent by thiamine in S. cerevisiae.

Actins↗

Inhibition of tumor necrosis factor-alpha production by orally administering a perilla leaf extract.

The overproduction of tumor necrosis factor-alpha (TNF-alpha) was suppressed by orally administering a perilla leaf extract (PLE). When mice were successively injected with OK-432, severe TNF-alpha was induced in the serum, but this elevated TNF-alpha level was reduced after an oral administration of PLE (400 microliters/mouse). Oral administration of PLE also inhibited TNF-alpha production that was induced by muramyl dipeptide (500 micrograms/mouse) and OK-432 (3 KE/mouse). These characteristics were obtained from all strains of perilla. The inhibitory activity against TNF-alpha production was heat-stable, and the existence of several active molecules was suggested. When PLE was passed through an ultrafilter, the inhibitory activity against TNF-alpha production was collected in those fractions with a mass of 0.5 to 1 kDa and more than 10 kDa. When PLE was solvent-extracted, the strongest activity was recognized with aqueous preparation, although significant activity was also detected in preparations extracted with n-hexane and ethyl acetate. These findings suggest that the daily use of certain functional foods may be useful for controlling the host defense system.

Animals↗

Analysis of extracellular matrix proteins in malignant chicken cell lines.

The adherent chicken cell line, MDCC-MSB1-41C, was highly transplantable and metastatic in vivo, compared with the parental non-adherent cell line MDCC-MSB1 from Marek's disease (MD) lymphoblastoid tumor. For clarification of differences in extracellular matrix proteins in MSB1-41C and MSB1 cells, examination was made of various components of extracellular matrix proteins. A detachment experiment indicated the protein(s) recognizing the Arg-Gly-Asp (RGD) sequence, the minimum structure required for recognition by the cell-surface receptors, is essential for the adherent character. Immunoblot assay using antibodies showed increased expression of fibronectin, fibronectin receptors, and vinculin on MSB1-41C cell lines. RGD-directed integrins mediate important cell-cell adhesive interaction and these interactions with extracellular matrix proteins may thus possibly be requisite for migration, proliferation and metastatic dissemination of MDCC-MSB1-41C cells. The RGD-containing peptide in the culture medium could cause detachment of cultured adhesive lymphoid leukosis LSCC-1104X5 cells from the dish too.

Amino Acid Sequence↗