Search PubMed⌕ Search

Biomedical subjects

M Katsuki

Publications and source records attributed to M Katsuki.

157 records · Page 9Linked to original sources
PubMed1987

Correlation of T cell receptor gene rearrangements to T cell surface antigen expression and to serum immunoglobulin level in scid mice.

The severe combined immunodeficient (scid) mouse which has undetectable serum immunoglobulin (Ig) contains a small number of thymic lymphocytes which express Thy-1 and IL2 receptors (IL2R) but not Lyt-2 or L3T4 molecules. These thymocytes did not show any rearrangement of T cell receptor (TCR) beta-chain genes. Such thymocyte characteristics in the scid mouse were similar to the 15-day embryonic thymocytes in ordinary mice, indicating that the scid mouse thymocytes are arrested in the early stage of intrathymic differentiation. However, low or medium level serum Ig was occasionally found in the littermates of the scid mouse. The thymocytes of these mice showed some evidence of TCR beta-chain gene rearrangement and the presence of Lyt-2+/L3T4+ cells in correlation with the serum Ig level. In the mice with some serum Ig the thymocyte cell number was increased and the proportion of IL2R+ cells was decreased. Collectively, these results suggest that the rearrangement of TCR beta-chain genes is associated with the expression of Lyt-2 and L3T4 molecules in intrathymic differentiation and probably with cell proliferation of the migrated lymphoid cells in the scid mouse.

Animals↗
PubMed1987

Specific expression of the chicken delta-crystallin gene in the lens and the pyramidal neurons of the piriform cortex in transgenic mice.

Two transgenic mice, 5-8 and 7-5, carrying the chicken delta-crystallin gene were produced by microinjecting cloned genes into male pronuclei. The mice were analyzed at 8 weeks of age with respect to gene integration and expression by means of blotting techniques and immunohistochemistry. Southern blot analysis indicated that both mice carried, on average, 50 copies of intact delta-crystallin gene per cell. Histological analysis of the mice using DNA-DNA in situ hybridization indicated that mouse 5-8 carried the delta-crystallin gene in every cell while mouse 7-5 was mosaic, with 20-40% of the cells of various tissues carrying the gene. Western blot analysis indicated that in both mice delta-crystallin is expressed in the lens and the cerebrum, but not in any other tissue examined. Immunohistological analysis revealed that, in the cerebrum of the mice, delta-crystallin was expressed specifically in pyramidal neurons located in layer IIb of the anterior piriform cortex. Thus, our results with transgenic mice not only demonstrate the primary specificity of delta-crystallin gene expression in authentic lens tissue, but reveal the unexpected specificity of this chicken gene in the central nervous system of the mouse.

Animals↗
PubMed1987

Future perspectives in the development of new animal models.

It is essential to develop animal models for human diseases with disease onset mechanisms the same as those of humans to study the causes, and therapeutic and preventive methods for human disease, as well as to develop new drugs. In the past, many beneficial experiments were performed by selecting animals with symptoms similar to those of humans from nature or breeding colonies. Experimental systems using induced disease models have been developed and provided useful results. The current basis of biology has reached the molecular level, and various phenomena of life have come to be understood through clarification of the expression of genes (DNA). Human diseases are one of these life phenomena, and the study of the relation between life phenomena and genes (DNA) has already started in the field of genetics. The next step appears to be the manipulation of genes to produce animal models for various human diseases. Progress has already been made in genetic and cellular engineering and embryonic manipulation on the basis of their respective methodologies and principles. One of the topics for future studies will be the development of models for human diseases through the integrated application of these fields. It is clear from documents on medical history that experiments using animals have been performed from the earliest period of ancient medical research. Therefore, pioneers in each period continued such studies and by the time of Claude Bernard, animal experiments had become an essential part of medical research. He stated in 1865 in his "Introduction to the Study of Experimental Medicine" that "I not only conclude that experiments made on animals from the physiological, pathological and therapeutic points of view have results that are applicable to theoretic medicine, but I think that without such comparative study of animals, practical medicine can never acquire a scientific character." Following this, animal experiments were widely performed in all fields of medical research, but the animals used in such experiments were only improved to the level they have reached today through the modernization movement which started in Europe, the United States and Japan from the end of the 1940's through the beginning of the 1950's. From the 1960's, the term "biomedical research" came into use in the United States to describe experiments using animals in the fields of medical research.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Teratocarcinoma derived from mouse zygotes after the introduction of activated human c-Ha-ras DNA.

We attempted to produce transgenic mice harboring the normal or activated human c-Ha-ras gene in order to examine the function of activated oncogenes in tumorigenesis. During the process of development, it happened that not only normal looking fetuses were obtained but also malformants, developmentally arrested conceptuses and tumors. Six such abnormally developed embryos were found to have been integrated with the activated human c-Ha-ras gene. One of the two tumors thus obtained was formed after the injection of 6.3 kb DNA fragment containing the gene for p21 with valine at the twelfth position. This tumor was integrated with two copies of the introduced DNA at a particular site in a chromosome and arranged in tandem in a head to tail direction. Histological analysis revealed that this tumor was constructed from at least three types of cells: two originating from different germ layers (one endoderm and the other mesoderm) and the third from an extra-embryonic ectoderm. The other tumor revealed similar features. Thus, it was strongly suggested that these tumors were derived from the very early developmental stage of the embryo, and had features very similar to those of teratocarcinoma.

Animals↗
PubMed1985

Molecular genetic analysis of myelin-deficient mice: shiverer mutant mice show deletion in gene(s) coding for myelin basic protein.

The gene expression of myelin basic proteins (MBPs) in shiverer mutant mice was investigated by the Northern and Southern hybridization techniques. In the control mice RNA molecules from the brains which were about 2,300 nucleotides in length were hybridized to cDNA of 1.8 kb encoding for a mouse MBP, but RNA from the brains of 3-week-old shiverer mutant mice contained no detectable amount of MBP transcripts hybridizing to this probe. Moreover the shiverer mutant mice lost several restriction fragments that hybridized to the same probe in the control mice when each of the five restriction enzymes, i.e., HindIII, PstI, PvuII, AccI, and StuI, was used. These data suggest that the shiverer mutation may correspond to the deletion of a large portion of MBP exon(s) in the gene, and this deletion causes inefficient transcription leading to the depletion of MBPs in the myelin and the dysmyelination observed in these mice.

Animals↗
PubMed1983

Developmental and sex-dependent regulation of storage protein synthesis in the silkworm, Bombyx mori.

The mechanism of sex-dependent expression of a major plasma protein, referred to as storage protein 1 (SP-1) was studied during development of the silkworm, Bombyx mori. SP-1 occurred in the hemolymph of the female as well as in the male larvae until the end of the fourth larval instar. In the last instar larvae, the amount of SP-1 in the hemolymph greatly increased in females, but markedly declined in males. The level of fat body mRNA for SP-1 reflected the developmental and sex-dependent changes in the hemolymph concentration of SP-1. The developmental patterns of hemolymph proteins in the third and the fourth instar larvae of sex-mosaic individuals were quite analogous to those observed in normal larvae at the same developmental stages. The hemolymph concentration of SP-1 at the last larval instar of the sex mosaics varied among individuals irrespective of the gonad compositions. In vitro culture of the fat body cells dissected from several locations of a sex-mosaic larva provided evidence that each fat body cell in a common hemolymph milieu synthesizes a high (female type) or a low (male type) level of SP-1 depending on the sex chromosome composition. The amount of vitellogenin in the hemolymph of the sex-mosaic pupae was in proportion to that of SP-1 at the last larval instar. From these results, it is suggested that the sex-dependent expression of SP-1 and vitellogenin in B. mori is genetically determined and developmentally regulated without participation of the reproductive organs or any sex-specific humoral factors.

Animals↗
PubMed1978

Distribution of ribonucleic acid coliphages in south and east Asia.

We investigated the distribution of ribonucleic acid (RNA) coliphages in the Philippines, Singapore, Indonesia, India, and Thailand by collecting sewage samples from domestic drainage in November 1976. Of the 221 samples collected from domestic drainage, 50 contained RNA phages (52 strains). By serological analysis, 46 of the 52 strains were found to belong to group III. It can thus be said that the most prevalent RNA phages in Southeast Asia (at least, in the Philippines, Singapore, and Indonesia) were group III phages. Investigations of sewage samples collected from domestic drainage in Japan indicate that the most prevalent RNA phages in mainland Japan (north of Kyushu) are group II phages, whereas group III phages are predominant in the southern part of Japan (south of Amamiohshima Island). We therefore propose a borderline between Kyushu and Amamiohshima Island for the geographical distribution of RNA coliphages in the domestic drainage of South and East Asia. Moreover, one strain (ID2) was inactivated to some extent with the antisera of four groups of RNA phages. This is thought to be significant from the evolutionary viewpoint.

Coliphages↗
PubMed1978

Escherichia coli gene that controls sensitivity to alkylating agents.

A new type of Escherichia coli mutant which shows increased sensitivity to methyl methane sulfonate but not to UV light or to gamma rays was isolated after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. The mutant is unable to reactivate phage lambdavir or double-stranded phiX174 DNA (replicative form) that had been treated with methyl methane sulfonate. The mutant is sensitive to other alkylating agents, such as ethyl methane sulfonate, mitomycin C, and N-methyl-N'-nitro-N-nitrosoguanidine, as well. It grows normally and exhibits almost normal recombination proficiency. The mutant possesses normal levels of DNA polymerase I, exonuclease I, exonuclease V, endonuclease specific for methyl methane sulfonate-treated DNA, and 3-methyladenine-DNA glycosidase activities. The genetic locus responsible has been named alk and is located near his on the chromosome.

Alkylating Agents↗
PubMed1975

Excision of pyrimidine dimers in normal and T4-infected Escherichia coli: effect of polA and other mutations.

Strains carrying both polA1 and recBts1 mutations, which are defective in DNA polymerase I and have thermolabile exonuclease V (the recBC enzyme), are viable at 30 degrees C but not at 42 degrees C. These mutants exhibit almost normal rate of dimer excision in vivo even at the restrictive temperature. Similar results were obtained with other polA minus strains. We have also investigated effect of host and phage mutations on excision of dimers in T4-infected cells. Only a small amount of dimer is excised in T4v-1-infected cells whereas an extensive and selective release of dimers takes place in T4D-infected cells. Other phage mutations, including mutations in gene 43 and gene 30, do not affect excision of dimers in infected cells.

Coliphages↗
PubMedDate not supplied

Blockage of alpha beta T-cell development by TCR gamma delta transgenes.

T lymphocytes recognize antigens by means of T-cell receptors (TCR) composed of alpha beta or gamma delta heterodimers. The mechanism governing the development of alpha beta- and gamma delta-bearing T cells from a common precursor T cell is so far unknown. It has been proposed that T-cell precursors rearrange their gamma- and delta-chain genes first, and alpha beta T cells are generated only from those cells that fail to rearrange productively both gamma- and delta-chain genes. Our recent study on gamma delta-transgenic mice contradicted this hypothesis, however, and indicated that repression of gamma-chain gene expression mediated by a transcriptional silencer element has a critical role in the generation of alpha beta T cells. Here we report that the generation of alpha beta T cells is severely blocked in transgenic mice carrying gamma- and delta-chain transgenes without the associated silencer, thereby strengthening the validity of the silencer model of T-cell development.

Animals↗
PubMedDate not supplied

Cell type-specific expression of the human renin gene.

We have previously produced transgenic mice carrying the human renin gene, whose expression is regulated in a tissue-specific manner. In the present study, we further characterized expression of the transgene. Northern blot analysis showed that the human renin gene is expressed in the kidney but not in the liver of two lines of transgenic mice with 10 and 50 copies of the transgene, suggesting that the integrated copy number of the human renin gene does not influence the dominant-renal expression pattern. Immunohistochemical study using a monoclonal antibody specific for human renin demonstrated that expression of human renin in the transgenic mouse kidney is confined to the epithelioid juxtaglomerular cells. Transfection experiments indicated that the chloramphenicol acetyltransferase fusion gene containing the 3-kb upstream sequences of the renin gene is activated only in human epithelioid embryonic 293 cells derived from kidney but not in human HepG2 cells from liver. These findings suggest that transfer of the cloned renin gene into mice and in vitro cultured cell lines can give rise to cell type-specific expression.

Animals↗