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Biomedical subjects

Y Yazaki

Publications and source records attributed to Y Yazaki.

At least 433 records · Page 24Linked to original sources
PubMed1996

Diversity of the synthetic-state smooth-muscle cells proliferating in mechanically and hemodynamically injured rabbit arteries.

Vascular smooth muscles contain at least three types of developmentally regulated myosin heavy-chain (MHC) isoforms; SM1, SM2, and SMemb. By investigating the expression of the three MHC isoforms, we previously demonstrated in rabbits that smooth muscles proliferating in the neointima of arterio- and atherosclerotic lesions regain an "embryonic" phenotype. In the present study, we examined if neointimal cells are morphologically similar to embryonal smooth muscles and if dedifferentiation of neointimal smooth muscles is a reversible process. Vascular injury was produced in rabbits either by endothelial cell denudation of the aorta or by poststenotic dilation of the carotid artery. We have demonstrated in this study that the proliferating neointimal cells expressed SM1 and SMemb, but not SM2, indicating smooth muscles of an "embryonic" phenotype. The dedifferentiation of neointimal smooth muscles was found to be reversible; at 4 to 8 weeks after injury, a majority of the cells reexpressed both SM1 and SM2, but not SMemb. By electron microscopy, we have revealed smooth-muscle phenotypes determined by MHC isoforms to correspond to the morphologic phenotypes as an increase in membranous organelles, and a decrease in myofilaments was associated with the reexpression of SMemb. Interestingly, we also found that in the medial wall at 4 to 8 weeks after ballooning injury, a number of SM1-negative cells proliferated rapidly, replacing normal smooth muscles. These cells were negative against SM1 and SM2 but positive for SMemb. These SM1-negative cells contained abundant membranous organelles and few myofilaments. These cells did not express SM1 or SM2 even after 8 weeks postinjury. We conclude from these results that the proliferating synthetic-type smooth muscles after vascular injury are composed of SM1-positive cells that are morphologically similar to embryonal smooth muscle and that maintain ability to redifferentiate, and SM1-negative cells that contain few myofilaments and remain dedifferentiated.

Age Factors↗
PubMed1996

Increased Evi-1 expression is frequently observed in blastic crisis of chronic myelocytic leukemia.

Evi-1 is a transforming gene originally identified in a common integration site of murine leukemia retrovirus and mapped in human chromosome 3q26. It is not normally expressed in either human or murine hematopoietic cells, but is overexpressed in retrovirus-induced murine myeloid leukemias as well as human myeloid leukemias with 3q26 abnormalities, and thus thought to be responsible for both human and murine leukemogenesis. In this study, possible involvement of the Evi-1 gene in human leukemias was evaluated by Northern blot analysis in a total of 73 patients with various types of leukemias. We found that increased expression of the Evi-1 gene was most frequently observed in patients with CML in blastic crisis. It was found in 10 of 14 (71.0%) samples from CML in blastic crisis, three of 15 (20.0%) from acute myelocytic leukemia, three of 11 (27.3%) from MDS-derived leukemia, and one of 11 (9.1%) from acute lymphoblastic leukemia. Among 18 patients showing increased Evi-1 expression, none of 17 informative patients showed cytogenetic abnormalities involving 3q26. In addition, Southern blot analysis revealed neither amplification nor rearrangements of the Evi-1 gene in 11 Evi-1-positive patients whose DNA samples were available. Our results suggest that increased expression of the Evi-1 gene may play an important role in development of human leukemias, especially in progression from chronic phase to blastic crisis of CML even without 3q26 abnormalities.

Adult↗
PubMed1996

Expression of costimulatory molecules in human leukemias.

In order to determine the indication of B7 (B7-1 and B7-2) molecules-mediated immuno-gene therapy for human leukemias, we investigated 94 human leukemic samples for the expression of MHC molecules required for tumor antigen-specific signals and of B7-1, B7-2, and ICAM-1 molecules required for non-specific costimulatory signals. All samples were strongly positive for MHC class I and 84% for class II antigen. B7-1, B7-2 and ICAM-1 were expressed in 5%, 22% and 16% of the total cases, respectively. Especially in 54 AML samples, B7-1 was only expressed in one case, while B7-2 was detected in as many as 15 cases (28%). We have also examined 13 human myelo/monocytic cell lines for the expression of class II and costimulatory molecules and found that significant expression of costimulatory molecules was induced in human leukemic cells by some suitable drugs, among which interferon-gamma (IFN-gamma) was the most potent inducer. Our results indicate that when the B7-mediated immuno-gene therapy was applied to human leukemias, especially to AML, B7-1 was rather preferable to B7-2 in that the latter was more widely expressed on human leukemic cells. Furthermore, since gene-transfer systems occasionally accompany serious problems, it should be taken into account that costimulatory molecules on human myelo/monocytic leukemic cells could be induced ex vivo without the introduction of exogenous genes.

Antigens, CD↗
PubMed1996

Hypertensive glomerular damage as revealed by the expression of alpha-smooth muscle actin and non-muscle myosin.

The aim of this study was to determine the phenotypic modulation in mesangial cells of glomeruli damaged by hypertension. Salt-loaded stroke-prone spontaneously hypertensive rats were untreated or treated with a calcium antagonist, manidipine (2 mg/kg/day) for eight weeks. In normotensive Wistar-Kyoto rats, alpha-smooth muscle actin was not expressed in any glomerular cells and a non-muscle myosin heavy chain isoform, SMemb, was slightly expressed in glomerular visceral epithelial cells. In the untreated hypertensive rats, the glomeruli showed sclerosis to various degrees and expressed alpha-smooth muscle actin and SMemb. Normal expression of SMemb in the epithelial cells disappeared. Notably, alpha-smooth muscle actin-positive fibroblast-like cells appeared in the interstitium, especially around the Bowman's capsules. Manidipine ameliorated the glomerulosclerosis and reduced the expression of alpha-smooth muscle actin in mesangial cells. In conclusion, the mesangial cells changed their phenotypes and expressed alpha-smooth muscle actin and SMemb in the glomeruli during the development of hypertensive renal damage. These phenotypically changed mesangial cells are considered to be activated and to produce various kinds of cytokines and extracellular matrix, which leads to glomerulosclerosis. Manidipine attenuated the glomerular damage and the phenotypic changes. The functional relevance of phenotypic changes in these cells should be elucidated in future studies.

Actins↗
PubMed1996

Three histologically different tiny gastric cancers developing adjacent to each other, resected endoscopically in a single mucosal piece.

In this report, we describe a case with triple tiny cancers of the stomach developing adjacent to each other and resected endoscopically in a single mucosal piece. The three cancers differed from each other histologically. The surrounding mucosa was atrophic pyloric gland mucosa with moderate to severe intestinal metaplasia. Both histological and serological examinations were negative for Helicobacter pylori. Each of the three cancer lesions was positive for mutant p53 product immunohistochemically. None of the cancers were positive for Epstein-Barr virus sequence in an in situ hybridization analysis. These lesions suggest that certain local conditions in the gastric mucosa can result in carcinogenesis of different histological types of gastric cancers.

Adenocarcinoma↗
PubMed1996

Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1 and identification of insulin receptor substrate-2.

To clarify the physiological roles of insulin receptor substrate-1 (IRS-1) in vivo, we made mice with a targeted disruption of the IRS-1 gene locus. Mice homozygous for targeted disruption of the IRS-1 gene were born alive but were retarded in embryonal and postnatal growth. They also had resistance to the glucose-lowering effects of insulin, insulin-like growth factor-1 (IGF-1) and factor-2 (IGF-2). These data suggest the existence of both IRS-1-dependent and IRS-1-independent pathways for signal transduction of insulin and IGFs. Moreover, we identified tyrosine phosphorylation of a 190-kDa protein (pp 190) as a novel substrate (IRS-2) for insulin receptor kinase in livers of IRS-1 deficient mice which can bind both P13-kinase and Ash/Grb2.

Animals↗
PubMed1996

Molecular genetic approach to the pathophysiology of cardiovascular disease.

The delineation of the molecular mechanisms of cardiovascular disease is an important initial step in developing improved methods of screening and therapy. Recently, progress has been made in characterizing the molecular basis of several inherited cardiovascular diseases, particularly as to the diseases caused by defects in single gene. When the disease under study has a complex etiology with multiple genetic and environmental components, it becomes much more difficult to dissect out the genetic factors and to distinguish between causation and correlation. Gene targeting in mice provides a means to test the effect of a precise genetic change completely free from the effects of differences in any other genes. Models of several human genetic diseases have been produced by gene targeting and the resulting "knockout" mice have often confirmed that the disease is the consequence of the defect of a gene of interest. The review will focus on the how molecular genetic approach is useful to understand the basic mechanism of complex genetic diseases, including essential hypertension, atherosclerosis, congenital heart disease. Particular emphasis will be given to the renin angiotensin system because a large body of evidence indicates its greater role in the pathogenesis of many complex cardiovascular diseases than has been recognized.

Animals↗
PubMed1996

Perforin-positive leukemic cell infiltration in the aortic tissue of a patient with T-cell prolymphocytic leukemia.

Here we report a rare case of T-cell prolymphocytic leukemia in which leukemic killer cells, expressing a cytolytic factor perforin, infiltrated the aorta as well as the heart and may have directly injured aortic vascular cells which strongly expressed human leukocyte antigens (HLAs) and intercellular adhesion molecule-1 (ICAM-1) as well as costimulatory molecules B7 and B70, which are ligands for CD28 expressed on T-cells. In spite of chemotherapy against leukemic cells, this autoimmune process finally caused fatal multi-organ failure.

Adult↗
PubMed1996

Tyrosine phosphorylation of p130Cas in cell adhesion and transformation.

Integrins comprise the major class of receptors used by cells to interact with the extracellular matrix. Integrin/matrix interactions play a critical role in a variety of biological processes, including embryonic development, wound healing, tumor metastasis, cell growth and differentiation. It is now evident that integrins can transduce biochemical signals across the plasma membrane to the cell interior. Protein tyrosine phosphorylation has attracted much attention as an important regulator for integrin-mediated signal transduction. Recently, we have identified a novel signaling molecule, p130Cas, which participates in integrin-mediated signal transduction. p130Cas was originally identified as a protein hyperphosphorylated in cells expressing transforming gene products p47v-crk (v-Crk) and p60v-crk (v-Src). In this brief review, we will discuss about a role of p130Cas in signal transduction triggered by cell adhesion and transformation.

Cell Adhesion↗