Kumamoto University

About: Kumamoto University is a education organization based out in Kumamoto, Kumamoto, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 19602 authors who have published 35513 publications receiving 901260 citations. The organization is also known as: Kumamoto Daigaku.

Chemokines in immunity.

Abstract: Chemokines are a superfamily of small, heparin-binding cytokines that induce directed migration of various types of leukocytes through interactions with a group of seven-transmembrane G protein-coupled receptors. At present, over 40 members have been identified in humans. Until a few years ago, chemokines were mainly known as potent attractants for leukocytes such as neutrophils and monocytes, and were thus mostly regarded as the mediators of acute and chronic inflammatory responses. They had highly complex ligand-receptor relationships and their genes were regularly mapped on chromosomes 4 and 17 in humans. Recently, novel chemokines have been identified in rapid succession, mostly through application of bioinformatics on expressed sequence tag databases. A number of surprises have followed the identification of novel chemokines. They are constitutively expressed in lymphoid and other tissues with individually characteristic patterns. Most of them turned out to be highly specific for lymphocytes and dendritic cells. They have much simpler ligand-receptor relationships, and their genes are mapped to chromosomal loci different from the traditional chemokine gene clusters. Thus, the emerging chemokines are functionally and genetically quite different from the classical "inflammatory chemokines" and may be classified as "immune (system) chemokines" because of their profound importance in the genesis, homeostasis and function of the immune system. The emergence of immune chemokines has brought about a great deal of impact on the current immunological research, leading us to a better understanding on the fine traffic regulation of lymphocytes and dendritic cells. The immune chemokines and their receptors are also likely to be important future targets for therapeutic intervention of our immune responses.

Escherichia coli FtsH is a membrane-bound, ATP-dependent protease which degrades the heat-shock transcription factor sigma 32.

Abstract: Escherichia coli FtsH is an essential integral membrane protein that has an AAA-type ATPase domain at its C-terminal cytoplasmic part, which is homologous to at least three ATPase subunits of the eukaryotic 26S proteasome. We report here that FtsH is involved in degradation of the heat-shock transcription factor sigma 32, a key element in the regulation of the E. coli heat-shock response. In the temperature-sensitive ftsH1 mutant, the amount of sigma 32 at a non-permissive temperature was higher than in the wild-type under certain conditions due to a reduced rate of degradation. In an in vitro system with purified components, FtsH catalyzed ATP-dependent degradation of biologically active histidine-tagged sigma 32. FtsH has a zinc-binding motif similar to the active site of zinc-metalloproteases. Protease activity of FtsH for histidine-tagged sigma 32 was stimulated by Zn2+ and strongly inhibited by the heavy metal chelating agent o-phenanthroline. We conclude that FtsH is a novel membrane-bound, ATP-dependent metalloprotease with activity for sigma 32. These findings indicate a new mechanism of gene regulation in E. coli.

Characterization of a human immunodeficiency virus neutralizing monoclonal antibody and mapping of the neutralizing epitope

Abstract: A monoclonal antibody was produced to the exterior envelope glycoprotein (gp120) of the human T-cell lymphotropic virus (HTLV)-IIIB isolate of the human immunodeficiency virus (HIV). This antibody binds to gp120 of HTLV-IIIB and lymphadenopathy-associated virus type 1 (LAV-1) and to the surface of HTLV-IIIB- and LAV-1-infected cells, neutralizes infection by cell-free virus, and prevents fusion of virus-infected cells. In contrast, it does not bind, or weakly binds, the envelope of four heterologous HIV isolates and does not neutralize heterologous isolates HTLV-IIIRF and HTLV-IIIMN. The antibody-binding site was mapped to a 24-amino-acid segment, using recombinant and synthetic segments of HTLV-IIIB gp120. This site is within a segment of amino acid variability known to contain the major neutralizing epitopes (S. D. Putney, T. J. Matthews, W. G. Robey, D. L. Lynn, M. Robert-Guroff, W. T. Mueller, A. J. Langlois, J. Ghrayeb, S. R. Petteway, K. J. Weinhold, P. J. Fischinger, F. Wong-Staal, R. C. Gallo, and D. P. Bolognesi, Science 234:1392-1395, 1986). These results localize an epitope of HIV type-specific neutralization and suggest that neutralizing antibodies may be effective in controlling cell-associated, as well as cell-free, virus infection.

Hormone-Induced Morphogenesis and Growth: Role of Mesenchymal–Epithelial Interactions

Abstract: Publisher Summary This chapter explains the role of mesenchymal–epithelial interactions in hormone induced morphogenesis and growth. The mechanism of steroid hormone action is thought to involve specific high-affinity receptor proteins. The hormone enters the cell, binds to the cytoplasmic receptor, which after activation translocates to the nucleus. The hormone–receptor complex in turn binds to nuclear acceptor sites on the chromatin. This activates a variety of metabolic processes, the most important being the stimulation of messenger RNA (mRNA) synthesis and the ultimate production of new proteins. The first indication that androgens can elicit their effects upon epithelial morphogenesis via the mediation of mesenchymal cells comes from studies in which urogenital epithelia from the embryonic seminal vesicle or urogenital sinus are grown in association with either urogenital mesenchyme or with non-target integumental mesenchyme. Urogenital mesenchyme induces specific epithelial morphogenesis, growth, and function within the genital tract and that the hormonal sensitivity of these morphogenetic processes resides in the mesenchyme that invariably contains nuclear hormone receptors. As morphogenetic processes are cyclic in adult genital tracts of many species, developmental properties are expressed in adulthood and, for this reason, appear to play a regulatory role in abnormal epithelial differentiation including carcinogenesis.

Nε-(Carboxymethyl)lysine Protein Adduct Is a Major Immunological Epitope in Proteins Modified with Advanced Glycation End Products of the Maillard Reaction†

Abstract: Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGE). Recent immunological studies have suggested the potential role of AGE in atherosclerosis, aging, and diabetic complications. We previously prepared a monoclonal (6D12) as well as a polyclonal anti-AGE antibody and proposed the presence of a common AGE structure(s) that may act as a major immunochemical epitope [Horiuchi, S., Araki, N., & Morino, Y. (1991) J. Biol. Chem. 266, 7329−7332]. The purpose of the present study was to determine the major epitope. Amino acid analysis of AGE−proteins indicated that Ne-(carboxymethyl)lysine (CML) was a major modified lysine residue. Immunologic studies demonstrated the positive reaction of 6D12 not only to all CML-modified proteins tested, but also to BSA modified with several aldehydes known to generate a CML−protein adduct, and a linear correlation between the CML contents of CML-BSA and their immunoreactivity to 6D12 up to ∼8 mol/mol of protein. Further e...