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Biomedical subjects

Y Yazaki

Publications and source records attributed to Y Yazaki.

At least 685 records · Page 38Linked to original sources
PubMed1992

Two myelodysplastic syndrome cases with the inv(11)(p15q23) as a sole chromosomal abnormality.

Two myelodysplastic syndrome cases (one with acute nonlymphocytic leukaemia (M2) transformed from myelodysplastic syndrome (MDS), and the other with chronic myelomonocytic leukaemia following refractory anaemia with excess of blasts in transformation) showed the inv(11)(p15q23) as a sole chromosomal abnormality. Gene probes for c-Ha-ras-1 and c-ets-1 were hybridized to metaphase cells from bone marrow of these patients. c-ets-1 gene, which is mapped to 11q23, was demonstrated to have translocated to the short arm in the rearranged chromosome 11 in both cases. On the other hand, c-Ha-ras-1 gene, which is located at 11p15, was translocated to the long arm in the rearranged chromosome 11 in patient 1, and deleted in patient 2. Our findings suggest that there may be heterogeneity in molecular events involved in the chromosomal rearrangement among the inv(11)-carrying MDS.

Adolescent↗
PubMed1992

Expression of glucose transporter isoforms with aging.

To elucidate the cellular mechanisms for impairment of glucose metabolism associated with aging, the facilitative glucose transporter protein and mRNA were studied in various tissues of young (7-week-old) and aged (20-month-old) rats. GLUT4 glucose transporter protein, a major glucose transporter isoform in the insulin-responsive tissues, was selectively decreased in the epididymal fat tissues of the aged rats compared with the young rats. This decrease is likely to be due to a decrease in protein synthesis rather than in protein stability, since GLUT4 mRNA per unit cellular total RNA was also decreased. GLUT4 mRNA in the skeletal muscle was rather increased in spite of the decreased level of GLUT4 protein in the aged rats, suggesting that the translational efficiency and/or stability of GLUT4 protein is decreased in the skeletal muscle of the aged rats compared with the young rats. In contrast to these alterations in GLUT4 expression, no apparent decrease in the GLUT1 protein amount was observed in the fat tissues, skeletal muscle and brain of the aged rats compared with the young rats. Thus, the tissue and isoform-specific alterations in glucose transporter expression are associated with aging and may contribute to impairment of glucose metabolism observed with aging.

Adipose Tissue↗
PubMed1992

Production of endothelin-1 in vascular endothelial cells is regulated by factors associated with vascular injury.

We studied the effects of factors associated with vascular injury on the production of endothelin-1 (ET-1) in cultured porcine aortic endothelial cells. ET-1 mRNA expression and peptide production in endothelial cells were increased by thrombin, transforming growth factor beta 1 (TGF beta 1), interleukin-1 (IL-1) and tumor necrotizing factor alpha (TNF alpha). The analysis of the enhancer/promoter region of the human ET-1 gene showed that the ET-1 gene transcription is regulated in a cell-specific manner and is activated by thrombin, TGF beta 1 and IL-1. These results suggest that the production of ET-1 in endothelial cells is regulated by factors associated with platelet aggregation, macrophage infiltration and the formation of atherosclerotic lesions.

Animals↗
PubMed1992

Plasma lipoprotein metabolism in transgenic mice overexpressing apolipoprotein E. Accelerated clearance of lipoproteins containing apolipoprotein B.

We have reported that transgenic mice overexpressing rat apo E shows marked reduction of plasma cholesterol and triglyceride levels due to the disappearance of VLDL and LDL. In this study, we investigated the metabolism of plasma lipoproteins in transgenic mice. After intravenous injection, the rates of clearance of 125I-VLDL and 125I-LDL were 3.0- and 2.4-fold greater in transgenic mice than in controls, respectively. Furthermore, clearance of chylomicron remnants estimated by oral retinyl palmitate-loading test was markedly enhanced in transgenic mice. The hepatic expression of LDL receptors by immunoblot analysis was similar in both groups. These data suggest that elimination of lipoproteins containing apo B was due to enhanced clearance of these lipoproteins enriched with apo E through hepatic LDL receptors. When fed a high cholesterol diet, controls showed twofold elevation of plasma cholesterol levels with marked increases in VLDL and LDL cholesterol on gel filtration chromatography. In contrast, cholesterol-fed transgenic mice showed resistance against these increases. High cholesterol feeding decreased the activity of hepatic LDL receptors and had no effect on enhancement of chylomicron remnant clearance in transgenic mice. Thus, overexpression of apo E facilitates metabolism of lipoproteins containing apo B presumably primarily via the LDL receptor pathway and possibly through an interaction with the chylomicron remnant receptor.

Animals↗
PubMed1992

Ouabain as an amplifier of mineralocorticoid-induced hypertension.

Ouabain has recently been reported to be an endogenous Na, K-ATPase inhibitor. To evaluate whether it exerts hypertensive action itself or amplifies the hypertensive action of small doses of mineralocorticoids, 5 mg deoxycorticosterone acetate (DOCA), 1 mg ouabain, or a combination of both were injected into mononephrectomized rats weekly for 6 weeks, and changes in blood pressure were evaluated. The blood pressures of control, DOCA-treated, ouabain-treated, and the combination treatment group at the sixth week were 138 +/- 3 (SE), 160 +/- 6, 144 +/- 6, and 201 +/- 14 mmHg, respectively. The blood pressure of rats given DOCA or ouabain alone was not significantly different from that of controls. In contrast, the blood pressure of rats given the combination of DOCA and ouabain was significantly higher than that of control rats and those given DOCA or ouabain separately. Cardionephromegaly and histopathological changes found in rats given the combination of DOCA and ouabain were consistent with the effects of an elevation of blood pressure. Further evaluation revealed that the amplification effect of ouabain on the hypertensive action of DOCA was dose dependent, with the minimum dose that caused the amplification effect being 0.25 mg/week. These results indicate that ouabain, although devoid of hypertensive action itself, amplifies the hypertensive action of small doses of DOCA and can cause a hypertensive state similar to that induced by larger doses of DOCA. It is inferred that the amplification effect of ouabain on mineralocorticoids is important in the genesis of hypertension.

Animals↗
PubMed1992

Detection of mutations in the human insulin gene by single strand conformation polymorphisms.

Single strand conformation polymorphisms (SSCP) is the method by which mutations can be detected in DNA amplified by the polymerase chain reaction (PCR). This method utilizes the fact that the electrophoretic mobility of single stranded DNA under nondenaturing condition depends not only on its size but also on its conformation. We examined whether this technique could detect five mutations that had previously been identified in the insulin genes of patients with abnormal insulin or familial hyperproinsulinemia. Five mutant insulin genes were constructed by site directed mutagenesis, and the cloned mutant insulin genes were amplified by PCR. All five mutations were detected because they were associated with shifts in the electrophoretic mobility of the DNA fragments. In addition, we analyzed amplified genomic DNA from a patient who is heterozygotes for the Insulin Wakayama mutation A3(Val----Leu). This mutation was also detected by the SSCP technique. We conclude that PCR-SSCP method is a simple, fast, and efficient method for detection of mutations in the human insulin gene.

Base Sequence↗
PubMed1992

Structure of the human glucokinase gene and identification of a missense mutation in a Japanese patient with early-onset non-insulin-dependent diabetes mellitus.

Glucokinase is thought to play a glucose-sensor role in the pancreas, and abnormalities in its structure, function, and regulation can induce diabetes. We isolated the human glucokinase gene, and determined its genomic structure including exon-intron boundaries. Structure of the glucokinase gene in human was very similar to that in rat. Then, by screening Japanese diabetic patients using polymerase chain reaction--single strand conformation polymorphism (PCR-SSCP) and direct-sequencing strategies, we identified a missense mutation substituting arginine (AGG) for glycine (GGG) at position 261 in exon 7 of the glucokinase gene in a patient with early-onset non-insulin-dependent diabetes (NIDDM).

Base Sequence↗
PubMed1992

Cellular and molecular bases for the immunopathology of the myocardial cell damage involved in acute viral myocarditis with special reference to dilated cardiomyopathy.

Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of the myocardial cell damage involved in viral myocarditis. To investigate the cellular and molecular bases of both target cells and effector cells for cell-mediated cytotoxicity involved in viral myocarditis and dilated cardiomyopathy, we first examined the expression of major histocompatibility complex (MHC) antigens and a cell adhesion molecule, intercellular adhesion molecule-1 (ICAM-1) in myocardial cells of a murine model of viral myocarditis and in patients with acute myocarditis and dilated cardiomyopathy. Secondly, we analyzed the characteristics of the infiltrating cells in the heart, especially the expression of a cytolytic factor, perforin. We found that Coxsackievirus B3 (CVB3)-induced murine acute myocarditis resulted in enhanced expression of MHC (class I) antigens and ICAM-1 on myocardial cells, and that perforin was abundantly expressed in NK (natural killer)-like large granular lymphocytes (LGL), which represent the main infiltrating cell type in the early stage. Immunoelectron microscopic study showed killer cells directly damaging cardiac myocytes by the release of perforin. Perforin was also expressed in the infiltrating cells in the heart of a patient with acute myocarditis. Both MHC antigens and ICAM-1 were clearly expressed in the hearts of patients with acute myocarditis and dilated cardiomyopathy. These data provided direct evidence that cell-mediated cytotoxicity plays a critical role in the myocardial cell damage involved in viral myocarditis.

Acute Disease↗
PubMed1992

Molecular mechanism of hypertrophied failing heart--abnormalities of the diastolic properties and contractility.

The clinical syndrome of heart failure occurs as a consequence of the limitation of compensatory mechanisms, such as cardiac hypertrophy. To clarify transcriptional changes in specific genes in failing hearts, we examined the expression of cardiac Ca(2+)+Mg(2+)-dependent ATPase in the sarcoplasmic reticulum and transforming growth factor beta genes in the ventricles of rat hypertrophied heart, and the expression of guanine nucleotide-binding protein and "fetal" contractile protein genes in the ventricles of cardiomyopathic Syrian hamsters of Bio14.6. Northern blot analysis of total cellular RNA revealed that the mRNA levels of Ca(2+)+Mg(2+)-dependent ATPase were decreased by pressure overload and became 32% of sham in 1 month, and were correlated with corresponding protein levels. Transforming growth factor beta mRNA, a potent activator of collagen synthesis, was increased by pressure overload. The expression levels of the Gs alpha mRNA, which stimulated the adenylate cyclase, in Bio14.6 ventricles were lower than the levels in ventricles of the F1B hamster strain, and decreased as the stage of cardiomyopathy progressed. Moreover, re-expression of fetal mRNA was observed in the ventricle of cardiomyopathic Syrian hamsters of the Bio14.6 strain. These results indicate that reprogramming of cardiac gene expression both of myofibrillar and nonmyofibrillar components might occur in the failing heart.

Animals↗
PubMed1992

Upregulation of GLUT2 mRNA by glucose, mannose, and fructose in isolated rat hepatocytes.

Previously, demonstrated that GLUT2 mRNA and protein are increased in liver of streptozocin-induced diabetic rats. To examine the mechanisms whereby GLUT2 mRNA is regulated, we cultured isolated hepatocytes in the absence and presence of various concentrations of glucose. Culture of hepatocytes in high glucose concentration (27.8 mM) for 20 h induced a 3.2-fold increase in GLUT2 mRNA levels compared with hepatocytes cultured without D-glucose. Interestingly, D-mannose and D-fructose could substitute for D-glucose to elevate the GLUT2 mRNA level, whereas 3-O-methyl-D-glucose, 2-deoxy-D-glucose, and sucrose, which were not metabolized or taken up by the cells, were without effect. Insulin had no significant effect on GLUT2 mRNA levels in hepatocytes in the presence or absence of D-glucose. Therefore, the regulation of the GLUT2 gene by D-glucose in hepatocytes is contrary to that reported for GLUT1 and GLUT4 genes, which are downregulated by D-glucose. These results also suggest that the elevated GLUT2 mRNA level observed in diabetic rat liver is due to the high blood glucose concentration rather than to insulin deficiency.

3-O-Methylglucose↗
PubMed1992

Relationship between autoepitope and DNA-binding site on a histone H1 molecule.

Autoepitope and DNA-binding domain on a histone H1 molecule were compared using truncated histone H1 peptides as antigens. At least two epitopes (epitope A, N-terminal side; epitope B, C-terminal side) were found both of which were composed of approximately 20 amino acids. IgM from all 17 anti-histone H1-positive SLE sera reacted with epitope A. IgG from 12 sera reacted with epitope A and IgG from 4 sera reacted with epitope B. In one case, no IgG anti-histone H1 reactivities were found while IgM from the same patient reacted with epitope A. Epitope A had the ability to bind DNA. The reactivities against histone H1 of affinity-purified antiepitope A autoantibodies were inhibited by DNA. These data suggest that some anti-histone H1 antibodies are directed against a histone H1 DNA-binding site, raising the possibility that an idiotype/anti-idiotype network, at least in part, is involved in the generation of anti-histone H1 autoantibodies.

Autoimmunity↗
PubMed1992

Detection of three separate DNA polymorphisms in the human lipoprotein lipase gene by gene amplification and restriction endonuclease digestion.

A rapid detection method was developed for DNA polymorphisms in the human lipoprotein lipase (LPL) gene. The examined polymorphisms include an A-C transversion in the 5'-region of intron 3, a T-G transversion that occurs within a Hind III site of intron 8, and the previously described C-T transition that causes a Pvu II polymorphism in intron 6. Gene fragments encompassing each polymorphic site were amplified by the polymerase chain reaction (PCR) and digested with an appropriate restriction enzyme whose recognition site was either naturally affected by the polymorphism or artificially created with a mismatched PCR-primer. According to the digestion profiles, genotypes were unambiguously distinguished. With this method, respective allelic frequencies were determined for 50 or 70 normal subjects. The procedure will facilitate LPL genotyping in the large population.

Base Sequence↗
PubMed1992

Treatment of acute nonlymphocytic leukemia by combination of recombinant human granulocyte colony-stimulating factor and cytotoxic agents: a report of six cases.

Six patients with recurrent and/or refractory acute nonlymphocytic leukemia (ANLL) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) and cytotoxic agents administered simultaneously. Neither of the two patients who received cytosine arabinoside (ara-C) in combination with G-CSF achieved complete remission. The other four patients, who received multi-drug combination therapy together with G-CSF, all achieved complete remission. No major side effects due to G-CSF were observed. These results demonstrated that the effects of G-CSF in enhancing the sensitivity of leukemic cells to cytotoxic agents and accelerating the recovery of leukocytes could lead to its possible use in the treatment of ANLL.

Adult↗
PubMed1992

Multiple strictures of the small intestine after long-term nonsteroidal anti-inflammatory drug therapy.

A 60-yr-old female patient with rheumatoid arthritis presented with nonsteroidal anti-inflammatory drug (NSAID)-induced ileal ulcers which caused intestinal bleeding and multiple strictures. Results of investigations, including radiological, pathological, and bacteriological examinations, were not consistent with Crohn's disease or intestinal tuberculosis. Rather, the lesion was characteristic of "diaphragm disease" caused by NSAIDs. Discontinuance of NSAIDs in combination with administration of ornoprostil (prostaglandin E1-derivative), sucralfate, and sulfasalazine put an end to the intestinal bleeding. This is a rate case of a patient with multiple strictures of the small intestine caused by NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗