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Biomedical subjects

M Katsuki

Publications and source records attributed to M Katsuki.

At least 145 records · Page 8Linked to original sources
PubMed1990

Anomalies in transgenic mice carrying the human interleukin-2 gene.

To elucidate the in vivo function of interleukin-2 (IL-2) we produced transgenic mice with either the human genomic IL-2 gene (hIL-2) or the murine metallothionein-I promoter-human IL-2 fusion gene (MThIL-2). Nine of 12 transgenic mice independently obtained showed motor ataxia (2 mice with hIL-2, and 7 mice with MThIL-2) due to the infiltration of lymphocytes into the cerebellar tissues (Katsuki et al. 1989). In addition to the ataxia shown by both groups of transgenic mice, other features were found with respect to each introduced DNA. The transgenic mice with hIL-2 suffered from alopecia. Lymphocytic infiltrates were found in the skin underlying the hairless regions as well as in the brains. On the other hand, the male transgenic mice with MThIL-2 had atrophic testes. In these male mice, sperm or cells of the later stages of spermatogenesis were depleted in the testes without any apparent signs of an immunological response. These findings suggest that the introduced human IL-2 genes may have the pleiotropic functions of inducing tissue-specific immunological responses in the brain and skin, and of having harmful effects on spermatogenesis.

Abnormalities, Multiple↗
PubMed1990

Most tumors in transgenic mice with human c-Ha-ras gene contained somatically activated transgenes.

Two independent transgenic mouse lines carrying human hybrid c-Ha-ras genes with their own promoter region encoding prototype products, were established. In these lines, about 50% of transgenic offspring had tumors within 18 months. The tumors developed in restricted tissues and about 60% of affected mice had angiosarcomas. The transgenes were expressed both in the tumors and in all normal tissues. However, somatic mutational activation was detected only in the transgenes of the tumors. The point mutation at the 61st codon, from CAG(Gln) to CTG(Leu), was detected in all angiosarcomas (22/22), some lung adenocarcinomas (3/11) and Harderian gland adenocarcinomas (4/7) in both lines. The other point mutation at the 12th codon from GGC(Gly) to GTC(Val) was detected in two of the four skin papillomas. No mutations on these codons were detected in normal tissues of transgenic mice. Nontransgenic littermates had no tumors at all. From these results, it was strongly suggested that the mouse tumors do not develop only by the expression of the transgenes, and that definite somatic point mutation of the human c-Ha-ras transgenes in certain cell types may be a causative event in tumorigenesis in these transgenic mice.

Animals↗
PubMed1989

Tissue-specific expression of the human renin gene in transgenic mice.

Transgenic mice carrying human renin gene were produced by microinjection of 15 kilobases (kb) DNA molecules with up to 3 kb of 5'-flanking sequence and 1.2 kb of 3'-flanking sequence. The transgenes have been shown to be stably transmitted to progeny. It was revealed by RNase protection assay that the human renin gene in a transgenic mouse is expressed preferentially in the kidney. The human renin RNA was also detected at a small level in a variety of tissues such as brain, heart, lung, pancreas, spleen, stomach, testis, and thymus. The direct radioimmunoassay using a monoclonal antibody specific for the active site of human renin demonstrated the synthesis of human active renin in the transgenic mouse kidney. These results suggest that the human renin gene in the transgenic mouse is regulated in a tissue-specific manner.

Animals↗
PubMed1989

T cell line specific for bacterial peptidoglycan subunit: possible role of the COOH-terminal amino acid of the disaccharide tetrapeptide in binding to the T cell receptor.

The T cell line specific for a bacterial cell wall peptidoglycan subunit, disaccharide tetrapeptide of diaminopimelic acid type, was examined for epitope specificity in elicitation of delayed-type hypersensitivity (DTH) in X-irradiated Lewis rats, using pairs of analogs different in optical configuration of the COOH-terminal amino acid. The test cell line induced DTH against analogs with the COOH-terminal D-amino acid but not against those with the L-amino acid at the COOH terminus. A close correlation was found between the T cell line-induced DTH reaction in vivo and the proliferative response in vitro, in terms of clear discrimination of the optical configuration of COOH-terminal amino acid of disaccharide tetrapeptide. The L-isomers (non-stimulatory analogs of T cell proliferation) competitively inhibited the proliferation of the T cell line by the corresponding D-isomers. Thus the L-isomers appear to interact with Ia molecules on antigen-presenting cells. We conclude that COOH-terminal D-amino acid of the disaccharide tetrapeptide could be involved in binding to the T cell receptor, induction of T cell proliferation, and elicitation of DTH.

Amino Acids↗
PubMed1989

Restoration of myelin formation by a single type of myelin basic protein in transgenic shiverer mice.

A minigene containing mouse cDNA coding for the smallest type of myelin basic protein and including the native promoter was constructed and used to produce transgenic shiverer mice. The hypomyelinating mouse, the shiverer, has a deletion in its myelin basic protein gene, lacks all four types of myelin basic protein in its myelin, and shows abnormal behavior such as violent tremors. Five of twenty-one transgenic shiverer mice showed recovered protein synthesis, compact myelin formation, and normal behavior. These results suggest that a single type of myelin basic protein restores myelin formation and returns the shivering phenotype to normal in the transgenic shiverer mouse.

Animals↗
PubMed1989

Lymphocyte infiltration into cerebellum in transgenic mice carrying human IL-2 gene.

We created transgenic mice with an intact human genomic interleukin-2 gene (gIL-2) or a mouse metallothionein-I promoter-human IL-2 chimeric gene (MTgIL-2). Nine (2 gIL-2 and 7 MTgIL-2 transgenics) out of 12 transgenic mice which were obtained independently had motor ataxic symptoms. All transgenic offspring of the symptomatic founders showed the same symptoms as their transgenic parents. Morphological examination demonstrated perivascular lymphocyte accumulation in the cerebellar meninx which was followed by increased cell infiltration of neutrophils and monocytes in the destructive cerebellum of all transgenic mice. These findings suggest that the lymphocyte infiltration in the cerebellum is caused by the specific effect of the exogenously introduced human IL-2 gene.

Animals↗
PubMed1989

A case of interstitial pneumonia antedating rheumatoid arthritis.

We describe a case report of an interstitial pneumonia in which pulmonary involvement of the both lower lobes mimicked idiopathic interstitial pneumonia (IIP) or bronchiolitis obliterans organizing pneumonia (BOOP). Its appearance antedated clinically apparent rheumatoid arthritis by one month and a half.

Adult↗
PubMed1989

Embryonal tumors from transgenic mouse zygotes carrying human activated c-Ha-ras genes.

To investigate the function of activated oncogenes we attempted to create transgenic mice carrying activated human c-Ha-ras genes which have their own promoters. However, we never obtained any transgenic pups which developed to term, because all transgenic embryos were malformed, became developmentally arrested conceptuses or developed embryonic tumors during ontogenesis. The mRNA expression of the transgenes was detected in two tumors obtained after introduction of the DNA fragment containing the activated human c-Ha-ras gene for p21 with valine at the 12th codon or with leucine at the 61st codon. Histological analysis indicated that each tumor consisted of at least three types of cells: two originating from different germ layers (the endoderm in one case and the mesoderm in the other) and the third from extra embryonic ectoderm. It was suggested that the activated human c-Ha-ras gene has a critical effect on the development of tumors in normal embryos as well as in transformation of NIH3T3 cells.

Animals↗
PubMed1988

Reduction of the adherence of Streptococcus sobrinus insoluble alpha-D-glucan by endo-(1----3)-alpha-D-glucanase.

Insoluble alpha-D-glucan, previously formed on a glass surface from sucrose by the action of cell-free D-glucosyltransferases of Streptococcus sobrinus OMZ176, was significantly removed by a purified preparation of endo-(1----3)-alpha-D-glucanase (mutanase) from a strain of Pseudomonas sp. Almost complete dissociation of adherent glucan occurred at the highest enzyme concentration (40 mU/mL) tested. Synthesis and de novo adherence on glass of the glucan was markedly inhibited by the presence of mutanase, even at low concentrations (4 mU/mL or less). When compared to native glucan, the mutanase-modified glucan samples (a) contained lower proportion of D-(1----3) linkages; (b) showed lower susceptibility to mutanase and higher susceptibility to (1----6)-alpha-D-glucanase (dextranase); (c) contained larger amounts of low-molecular-weight fractions; (d) had lower intrinsic viscosities; (e) showed higher S. sobrinus cell-agglutinating activities; and (f) consisted of looser entwinement of coalescent single-stranded fibrils (a major component) and shorter double-stranded fibrils (a minor one).

Adhesiveness↗
PubMed1988

Conversion of normal behavior to shiverer by myelin basic protein antisense cDNA in transgenic mice.

Myelin basic proteins (MBPs) are coded by the single gene necessary for myelin formation in the central nervous system of the mouse. An antisense MBP mini-gene was constructed and used to determine the function of antisense DNA in transgenic mice. Several transgenic offspring of a founder transgenic mouse, AS100, were converted from the normal to mutant shiverer phenotype. Antisense MBP messenger RNA was expressed in these mice, and the endogenous MBP messenger RNA, the MBP, and the myelination in the central nervous system were reduced.

Animals↗
PubMed1988

Isolation of T cell line capable of protecting mice against collagen-induced arthritis.

A T cell line specific to human type II collagen (CII) was selected and propagated from DBA/1J mice immunized with human CII. The line cells were not reactive to type I or type III collagen of human origin, but they were cross-reactive to bovine, rat, and rabbit CII and they recognized both native and heat-denatured human CII. The cells were reactive to an N-terminal three-quarters fragment of human CII, produced by tadpole collagenase digestion of human CII, but not to a C-terminal one-quarter fragment of human CII. The cells showed Thy-1+, Lyt-1+, Lyt-2-, and L3T4+ phenotypes characteristic of T helper cells or delayed-type hypersensitive cells, determined by the immunofluorescence method. To clarify the role of T cells in the pathogenesis of collagen-induced arthritis, we inoculated this cell line into DBA/1J mice and found that they developed clinical arthritis, albeit at a low incidence. The cells attenuated by x-ray were capable of inducing resistance to the subsequent induction of collagen-induced arthritis of DBA/1J mice. The sera from mice protected by inoculation of the cell line exhibited anti-idiotypic antibody response against conventional and monoclonal anti-CII antibodies. Anti-T cell receptor response may be involved in the mechanism for the protective effect of the cell line against autoimmune murine arthritis.

Animals↗
PubMed1988

Transgenic mice as systems for analyses of biological functions.

Recent advances in biotechnologies have made it possible to manipulate mammalian embryos. This technology in combination with the recombinant DNA technology provides embryos with new and purpose oriented genetic information. Subsequent embryo transfer to the pseudopregnant females also makes these manipulated embryos develop to term as transgenic animals. Transgenes integrated in the transgenic animals are usually transmitted to their offspring according to the Mendel's Law. Therefore, once we obtained a particular transgenic animal, we could rear them as a strain non-existent in nature. In this report, methods of producing transgenic mouse and a few examples which were applied to the analyses of biological functions are mentioned.

Animals↗
PubMed1988

Isolation and physiological characterization of Streptococcus milleri strains from human dental plaque.

Of 271 Gram-positive, catalase-negative, chain-forming cocci isolated from crevicular and supragingival plaques of 22 adults, 71 stains were clustered as Streptococcus milleri by testing 23 physiological characters. Most of the oral S. milleri strains were nonhaemolytic and formed minute smooth colonies on glucose and sucrose agar plates, while some of the clinical strains were alpha-haemolytic, forming rough colonies on Carlsson's MC agar plate as well as carrying the Lancefield group antigens C, F or G. The strains were divided into two biotypes, and further into six subtypes by their abilities to ferment maltose, salicin and/or lactose. Distribution of the varieties according to the haemolytic, colonial and serological properties among the oral isolates generally corresponded to the tentative biological types of S. milleri.

Adult↗
PubMed1987

Induction of delayed-type hypersensitivity by the T cell line specific to bacterial peptidoglycans.

A T cell line specific for the chemically well-defined peptidoglycan of bacterial cell wall, disaccharide tetrapeptide, was established from Lewis rats immunized with the antigen covalently linked to the autologous rat serum albumin. The antigen specificity was examined with various analogues or derivatives of the peptidoglycan. The cell line was reactive to analogues with the COOH-terminal D-amino acid, but least reactive to those with L-amino acid as COOH terminus. Transferring of the T cell line into X-irradiated normal Lewis rats induced delayed-type hypersensitivity in an antigen specific manner.

Animals↗