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Biomedical subjects

M Katsumata

Publications and source records attributed to M Katsumata.

At least 37 records · Page 2Linked to original sources
PubMed1996

TCR-beta transgenic mice fail to mediate a GVHR due to defects of allorecognition and subsequent IL-2 generation.

All T cells of TCR-beta transgenic mice bear a single TCR-beta chain and consequently the diversity of the TCR may be reduced by as much as one million-fold. Despite this limited diversity, many measures of lymphocyte function in these mice are normal. We have previously demonstrated that lymphoid cells from TCR-beta mice are unable to mediate an intense graft-versus-host response (GVHR). In order to investigate the mechanism of this hyporesponsiveness, we studied in vivo allorecognition in diverse strains of TCR-beta mice. All tested strains of TCR-beta mice failed to mediate a substantial GVHR across multiple H-2 barriers. In addition, mixtures of cells from several strains of TCR-beta mice only generated mild GVHRs. Sensitive tests of in vitro allorecognition show that lymphoid cells from TCR-beta mice respond less vigorously to alloantigen as measured both by decreased proliferation and decreased IL-2 production in a MLR. In addition, cells from TCR-beta mice fail to use exogenous IL-2 appropriately in their response to alloantigen. We conclude that the fixed TCR-beta chain causes a defective response to alloantigen, which is measured as decreased IL-2 generation and utilization, and that this abnormality results in a decreased GVHR.

Animals↗
PubMed1995

Moloney murine leukemia virus infection accelerates lymphomagenesis in E mu-bcl-2 transgenic mice.

E mu-bcl-2 transgenic mice bearing the bcl-2 proto-oncogene linked to the immunoglobulin enhancer (E mu) sporadically develop B or T cell lymphomas after a long latent period. To identify genes that play important roles in development of lymphoid malignancies, proviral insertional mutagenesis with Moloney murine leukemia virus (MMuLV) was carried out in two lines of transgenic mice expressing the bcl-2 gene primarily in B or T cells. MMuLV infection of non-transgenic mice induced primarily mature T cell lymphomas. By contrast, infection of newborn E mu-blc-2 mice with the virus accelerated lymphomagenesis, and nearly all of the mice eventually succumbed to clonal pre-B, B, or mainly immature T cell lymphoma, indicating the active contribution of the bcl-2 gene in lymphomagenesis. Southern blot analysis of tumor DNA from MMuLV-infected transgenic mice revealed a proviral insertion at the c-myc gene in 26% (9/35) of tumors, at the pim-1 gene in 6% (2/35) and at the pim-2 (recently renamed tic-1) gene in 23% (8/35). Some tumors carried two activated oncogenes. No insertion was detected at the bmi-1 gene. These data suggest the usefulness of this transgenic system for analysis of lymphomagenesis involving the activated bcl-2 gene.

Aging↗
PubMed1995

Relationship between bcl-2 and myc gene expression in human neuroblastoma.

We have investigated the relationship between the expression of bcl-2 and myc family genes in primary human neuroblastoma (NB) tumors and cell lines. Of 20 NB tumors examined, bcl-2 transcripts were expressed at variable levels in 16 tumors of all clinical stages. Of the 2 tumors with N-myc amplification, one expressed bcl-2 at a high level, whereas the other did so at a low level. In contrast, all NB tumors showed the expression of c-myc and/or N-myc transcripts. Similarly, of 9 NB cell lines with N-myc amplification examined, 6 expressed bcl-2 at high levels, whereas the other 3 expressed it at barely detectable levels. The 3 cell lines without N-myc amplification also expressed bcl-2 protein at high levels. All NB cell lines tested expressed either c-myc or N-myc protein. These data suggest that in NB, there is no significant association between bcl-2 expression and advanced tumor stages or N-myc amplification. The data also show that bcl-2 expression does not always coincide with myc expression in NB, suggesting that bcl-2- independent mechanisms may exist in the bcl-2-negative NB tumor cells in order to suppress the cell death promoting action of high myc expression.

Cell Cycle↗
PubMed1995

Prevention of breast tumour development in vivo by downregulation of the p185neu receptor.

Certain strains of transgenic mice that express the rat neu oncogene (neuT) in mammary epithelial cells develop breast tumours at an average of 44 weeks of age. In this study, intraperitoneal injection of a monoclonal anti-receptor antibody specific for the rat neuT oncogene product dramatically affected tumour development in these transgenic mice in a dose-dependent manner. A significant proportion (50%) of mice, when injected with anti-receptor antibodies, did not develop tumours even after 90 weeks of age. The phosphotyrosine levels of the membrane fraction of breast tissues in the anti-receptor antibody-treated mice were almost completely abolished when a higher dose of antibodies was used. This study demonstrates, for the first time, that immunologic manipulation of an oncogene product can effectively prevent the development of tumours in a rodent transgenic model.

Animals↗
PubMed1994

Oleanolic acid saponins from root bark of Aralia elata.

Three new oleanolic acid glycosides, tarasaponins I-III, were isolated as their methyl esters from the root bark of Aralia elata together with four known glycosides, the methyl esters of chikusetsusaponins IVa, IV, 28-desglucosyl-chikusetsusaponin IV and pseudoginsenoside RT1. Tarasaponins I-III were characterized as oleanolic acid 3-O-[beta-D-glucopyranosyl(1-->3)][alpha-L-arabinofuranosyl(1-->4)[- beta-D-glucuronopyranoside, oleanolic acid 3-O-[beta-D-xylopyranosyl(1-->2)][beta-D-galactopyranosyl(1-->3)]-beta- D-glucuronopyranoside and beta-D-glucopyranosyl oleanolate 3-O-beta-D-galactopyranosyl(1-->3)-beta-D-glucuronopyranoside, respectively.

Carbohydrate Sequence↗
PubMed1994

Expression of bcl-2 in small cell lung carcinoma cells.

We have investigated the expression of bcl-2 protein in a panel of small cell lung carcinoma (SCLC) cells lines. Five of six cell lines examined expressed relatively high levels of bcl-2 protein and transcripts. The bcl-2 expression in SCLC cells, however, was not always associated with myc expression. Since dysregulation of bcl-2 may be involved in the course of tumorigenesis and/or in the acquisition of drug resistance of tumor cells, the expression of bcl-2 in SCLC cells may become an important indicator in the prognosis or treatment of SCLC.

Carcinoma, Small Cell↗
PubMed1994

Oleanolic acid saponins from root-bark of Aralia elata.

Five new oleanolic acid glycosides, tarasaponins III-VII, were isolated from the dried root-bark of Aralia elata together with stipuleanoside R2, in addition to eight saponins previously reported. They were characterized as oleanolic acid 3-O-[beta-D-xylopyranosyl(1-->2)] [beta-D-glucopyranosyl(1-->3)]-alpha-L-arabinopyranoside, beta-D-glucopyranosyl oleanolate 3-O-[beta-D-glucopyranosyl(1-->2)][alpha-L-arabinofuranosyl (1-->4)]-beta-D-glucuronopyranoside, beta-D-glucopyranosyl oleanolate 3-O-[beta-D-xylopyranosyl(1-->2)][beta-D-galactopyranosyl (1-->3)]-beta-D-glucuronopyranoside, beta-D-glucopyranosyl oleanolate 3-O-[beta-D-xylopyranosyl(1-->2)][beta-D-glucopyranosyl (1-->3)-alpha-L-arabinopyranoside, respectively.

Carbohydrate Sequence↗
PubMed1994

[An industrial toxicological study on workers who synthesize aminophenol and anisidine from chloronitrobenzene].

Aromatic nitro- and amino-compounds (ANA) are notorious methemoglobin forming substances. From 1987 to 1993, the author surveyed the exposure level to ANA and health status of workers in a chemical industry where they synthetize nitrophenol and anisidine from chloro-nitrobenzene. The ANA exposure indicator was the diazo-reaction positive substance in the worker's urine (Dz) and the biological effect of ANA was monitored through the methemoglobin concentration in the blood (MHb). The following results were obtained from the survey. 1. Both the Dz and MHb values tended to become lower between 1987 and 1993. 2. The MHb levels of the workers were a little higher than the control levels, and the difference between the values was statistically significant (p < 0.01); both levels were, however, within the normal range. 3. The MHb value was estimable from a mathematical model: MHb = (k1-k2/a) x DU x CH, where k1 and k2 were constants and a, DU and CH indicated the activity of glutathione S transferase in erythrocytes (GST), DZ in urine and blood hemoglobin concentration, respectively. The correlation coefficient of the multiple regression was statistically significant (R2 = 0.263, p < 0.01). This model suggests that the biotransformed fraction of ANA in the pulmonary uptake site, the lung, could not penetrate into erythrocytes or act as an MHb former. The model seemed to be consistent and valid when urinary DZ values were less than 1.0 (mg/mg creatinine) and MHb values were less than 2.0 (mg/ml blood). Thus, the upper limit of normal levels for MHb can be considered to be 2.0 (mg/ml blood), or 12-1.6% of total hemoglobin in blood. 4. The significance of the uptake sites, i.e., lung, skin etc., was discussed with reference to the evidence obtained from the longshoremen cases, who were percutaneously exposed to chloronitrobenzene in 1984. 5. Hemolysate solutions from the blood of workers were applied to isoelectric focusing electrophoresis (IEF), and Hb species of different valencies were separated; intermediate MHbs, where the heme iron in one of the components of Hb, i.e., in the alpha or beta chain was oxidized and MHb where both the alpha and beta chain heme iron oxidized and Hb X and Y, were separated and easily discernible. The correlation matrix was calculated using the data relevant to IEF and other indicators; MHb estimated spectrophotometrically, GST activity of erythrocytes, Hb and urinary DZ vale. The statistical procedure of principal component analysis was applied to the matrix, and two major principal components were extracted from the calculation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Two separate mechanisms of T cell clonal anergy to Mls-1.

T cell tolerance to superantigen can be mediated by clonal anergy in which Ag-specific mature T cells are physically present but are not able to mount an immune response. We induced T cell unresponsiveness to minor lymphocyte stimulations locus antigen (Mls)-1a in mice transgenic for TCR V beta 8.1 in three different systems: 1) injection of Mls-1a spleen cells, 2) mating with Mls-1a mice, and 3) bone marrow (BM) chimeras in which Mls-1a is present only on nonhematopoietic cells. CD4+8-V beta 8.1+ cells from all these groups did not proliferate in response to irradiated spleen cells from Mls-1a mice. We compared the response of these cells by T cell/stimulator cell conjugate formation, Ca2+ mobilization, and proliferation assays. The mechanisms underlying the unresponsiveness of these T cells appear to differ. CD4+8-V beta 8.1+ cells from Mls-1a spleen cell-injected mice mobilized cytoplasmic Ca2+ but proliferated at a reduced level in response to cross-linking with anti-TCR mAb. However, these cells formed conjugates, mobilized Ca2+, and proliferated in response to Mls-1a when activated B cells were used as stimulators, although they produced reduced levels of IL-2. In Mls-1a/b V beta 8.1 transgenic mice, a subset in CD4+8-V beta 8.1+ cells did not mobilize cytoplasmic Ca2+ after TCR cross-linking. Their conjugate formation, Ca2+ mobilization, or proliferation in response to Mls-1a on activated B cells was undetectable. Finally, CD4+8-V beta 8.1+ cells from the BM chimeras proliferated to TCR cross-linking at a partially reduced level and formed conjugates, mobilized Ca2+, and proliferated in response to Mls-1a on activated B cells. These features suggest that the mechanisms underlying the maintenance of anergy in Mls-1a spleen cell-injected mice are distinct from those in Mls-1a mice.

Animals↗
PubMed1993

Inhibitory action of chloramine on formate-metabolizing system. Studies suggested by an unusual case record.

We previously reported on a patient exposed simultaneously to methyl chloride and chloramine gas who developed metabolic acidosis and permanent blindness [M. Minami et al., Hum Exp Toxicol 11: 27-34, 1992]. The case report suggested the possibility of potentiation of methyl chloride toxicity by chloramine. The potentiating mechanism was investigated by exposing mice to methyl chloride followed by ammonia chloramine, and then the level of formate in urine samples was measured with an enzyme coupling method to detect disturbance of formate metabolism. Mice dosed with 0.05 mL 1.0 mM chloramine after methyl chloride exposure excreted a significantly larger amount of urinary formate than mice treated with only methyl chloride. There was no difference in urinary formate levels between mice treated with only 0.05 mL 1.0 mM chloramine and those given only the vehicle (0.1 M phosphate buffer pH 6.0) for chloramine. The underlying biochemical mechanism of deterioration of formate metabolism was found to be the inhibition of the enzyme, N10-formyl tetrahydrofolate (N10-f-THF) dehydrogenase by 0.56-3.35 microM chloramine in the in vitro experiment using the purified enzyme. Positive control mice, given orally 0.1 mL 10% methanol in 0.1 M phosphate buffer (pH 6.0) excreted the same amount of urinary formate as those receiving 0.05 mL 1.0 mM chloramine after methanol administration. This was ascribed to the inhibitory effect of chloramine on formaldehyde dehydrogenase and depletion of substrate for further metabolism. The inhibition of the enzyme by chloramine (2.7-100.8 microM) was confirmed by in vitro experiments, using the purified enzyme, formaldehyde dehydrogenase.

Aldehyde Oxidoreductases↗
PubMed1993

Frequent deletion of the transgene in T cell receptor beta chain transgenic mice.

TCR V beta 8.1 transgenic mice were generated using a genomic TCR V beta gene construct under the control of its promoter and enhancer. Among three lines of transgenic mice, one line expressed the transgenic TCR on only approximately 70% of peripheral T cells, while the other two lines expressed it on almost all mature T cells. T cells which lacked expression of the transgenic TCR beta chain expressed endogenous TCR beta chains. The molecular basis underlying the lack of transgene expression in T cells of this line of transgenic mice was investigated. The transgenic TCR- cells were isolated by two methods. First, Thy-1+ V beta 8.1/8.2- cells were purified from peripheral T cells using cell sorting. Second, transgenic TCR- T cell clones were established. In both cases, Southern blotting indicated that V beta 8.1- T cells had deleted the transgenic TCR gene. Thus, deletion of the transgenic TCR can occur in a high proportion of T cells, which allows rearrangement and expression of endogenous TCR beta chains.

Animals↗
PubMed1993

Rises in urinary bicarbonate contents and pH of adult Tokyo citizens.

Urinary bicarbonate has been considered to be negligible, and the pH of urine to be low (around pH 5.5) for these fifty years. It was, however, found that the contents of bicarbonate and pH of the urine of adult Tokyo citizens (435 adults including 148 males and 287 females) substantially increased. The findings may be correlated with increased inhaled amounts of carbon dioxide which finally causes the increase of urinary excretion of bicarbonate, though evidence that the gas accumulates in the atmosphere of Tokyo due to air pollution has not been directly demonstrated.

Adult↗
PubMed1992

Differential effects of Bcl-2 on T and B cells in transgenic mice.

We have produced bcl-2 transgenic mice by using a construct which mimics the t(14;18) translocation in human follicular lymphomas. Although lymphoid tissues from all transgenic mice contained high levels of human Bcl-2 protein, transgene expression was differentially regulated within the B- and T-cell compartments of lines derived from various founder mice. We have characterized the phenotypes of two lines of bcl-2 transgenic mice (line 2 and line 6) in which bcl-2 transgene expression was restricted primarily to the T- or B-cell lineages, respectively. Analysis of line 6 lymphocytes revealed a polyclonal expansion of B cells, and these B cells exhibited prolonged survival in vitro. In line 2 mice, numbers of T cells in the peripheral lymphoid tissues were more moderately elevated despite enhanced T-cell survival in vitro. Line 2 transgenic mice also showed significantly increased proportions of thymocytes with a mature phenotype. Taken together, these findings suggest different roles for bcl-2 in the in vivo regulation of B- and T-cell development and homeostasis.

Animals↗