Search PubMed⌕ Search

Biomedical subjects

T Kataoka

Publications and source records attributed to T Kataoka.

At least 199 records · Page 11Linked to original sources

Adenylate cyclases in yeast: a comparison of the genes from Schizosaccharomyces pombe and Saccharomyces cerevisiae.

A Schizosaccharomyces pombe gene encoding adenylate cyclase has been cloned by cross-hybridization with the Saccharomyces cerevisiae adenylate cyclase gene. The protein encoded consists of 1692 amino acids and has adenylate cyclase activity that cannot be activated by the Sa. cerevisiae RAS2 protein. Sc. pombe cyclase has a high degree of homology (approximately 60%) with the catalytic domain of Sa. cerevisiae cyclase precisely mapped by a gene-deletion analysis. A 25-40% identity is observed throughout the middle segments of approximately 1000 residues of both cyclases, large parts of which are composed of repetitions of a 23-amino acid motif similar to those found in human glycoproteins, Drosophila chaoptin, and Toll gene product. However, a segment corresponding to the NH2-terminal 620 residues of Sa. cerevisiae cyclase appears lost from Sc. pombe cyclase, and the COOH-terminal 140 residues are not well conserved between the two yeast species. Deletions involving the COOH-terminal residues of Sa. cerevisiae cyclase cause loss of activation by the RAS2 protein. These results suggest that Sc. pombe cyclase may have lost the ability to interact with RAS proteins by the loss of a regulatory site.

Adenylyl Cyclases↗

Synthesis and analgetic activity of sulfur-containing morphinans and related compounds.

3-Acylthiomorphinans, 3-carbamoylthio-3-deoxydihydromorphine and 3-benzoylthio-9-aza-17-carbamorphinan were synthesized by Newman-Kwart rearrangement of the corresponding O-thiocarbamates. The analgetic activities were lower than that of pentazocine, and the opioid receptor binding affinities were very weak. These acylthiomorphinans showed low antinociceptive activity compared with corresponding sulfur-containing benzomorphans. 3-Carbamoylthio-deoxydihydromorphine had no significant analgetic activity.

Analgesics↗

Synthesis and analgesic activity of novel heterocycles, [1]benzothiopyrano[3,4-b]pyrrole derivatives.

In order to develop analgesic compounds possessing a sulfur atom in the alicyclic ring, novel cis-fused heterocycles, [1]benzothiopyrano[3,4-b]pyrrole derivatives (II) were synthesized via a unique cyclization reaction starting from 4-(4-methoxyphenylthio)-2-butanone (1) or 6-methoxy-3,4-dihydro-2H-1-benzothiopyran-4-one (7). The analgesic effects of benzothiopyranopyrroles (16, 18) were measured by means of the writhing test. The phenolic derivative 18 completely inhibited the appearance of writhing at the dose of 50 mg/kg, but the methoxy derivative 16 had no analgesic effect.

Analgesics↗

Facile synthesis of 8-benzoylthio-2,6-methano-3-benzazocines and 3-benzoylthiomorphinans having small-ring substituents.

Synthesis of 3-cyclopropylmethyl-, 3-cyclobutylmethyl-, and 3-methyl-8-benzoylthio-2,6-methano-3-benzazocines (1j-l) was performed by regio-selective chlorosulfonation of non-narcotic 8-deoxy derivatives (1a-c) followed by reduction and benzoylation. 3-Benzoylthiomorphinans (2h-j) were also obtained by the same method. Compounds having small-ring substituents (1k, 1l, 2i, 2j) were found to be weak but pure mu- and delta-opioid antagonists. The analgetic activity of 1k was almost equal to that of pentazocine.

Analgesics↗

Shrinkage of rat mandibular acinar cell with acetylcholine detected by video-enhanced contrast microscopy.

Changes in acinar cell volume during secretion were observed in the perfused rat mandibular gland by the video-enhanced contrast (VEC) microscopy. The acinar cell shrank (81.3 +/- 4.9% (mean +/- S.D., n = 5] during acetylcholine stimulation and swelled (107.4 +/- 2.3% (n = 5] after cessation of the stimulation. These evidences suggested that a large amount of fluid is transported via transcellular route in the salivary gland.

Acetylcholine↗

[Activation of macrophages with Hochu-ekkito].

We attempted to analyse the mode of action of Hochu-ekkito on host defense mechanism, especially the effect of the drug on macrophage activation. Peptone-induced murine peritoneal exudate macrophages were incubated with/without Hochu-ekkito and interferon-gamma (IFN-gamma) for 16 hours at 37 degrees C, and then the supernatants harvested were assayed for the activities of TNF, IL-1 and prostaglandin E2. Cytotoxic activity of the macrophages against 51Cr-labeled EL-4 tumor cells was also assayed. It was found that Hochu-ekkito rendered macrophages cytotoxic against EL-4 cells. Hochu-ekkito also augmented the production of TNF, IL-1 or Prostaglandin E2 from macrophages. Synergistic effect of IFN-gamma for augmenting production of TNF or cytotoxic activity was noted. These results suggested that Hochu-ekkito activated macrophages directly in vitro.

Animals↗

Environmental conditions favorable for tumor progression in peritoneal cavity induced by peritoneal cells without tumor selectivity.

The incidence of the lethal growth of 10(1) L1210 murine leukemia cells in mice was higher in intraperitoneal (i.p.) (97%) than in intradermal (i.d.) (17%) inoculation, and survival time of mice was shorter in i.p. than i.d. inoculation. It was supposed that resident peritoneal cells (PC) enhanced tumor progression. I.d. inoculation of 10(1) L1210 cells mixed with 10(6) PC induced a lethal tumor growth at higher incidence than that of 10(1) L1210 cells alone or the mixture of 10(1) L1210 cells and 10(4) peripheral blood mononuclear cells (PBM) did. Furthermore, co-inoculation of a tumorigenic number of L1210 cells (10(3] with 10(6) PC resulted in marked shortening of median survival time of mice. Similar growth enhancing effect of PC was observed in Meth 1 fibrosarcoma. Meth A fibrosarcoma and colon carcinoma 26 (C26). Further study showed that PC, intact or X-rayed, helped the in vitro tumor growth under the conditions in which L1210 alone did not grow at all, whereas PBM had no enhancing effect to L1210 growth. We characterized the cells involved in tumor growth enhancement by the in vivo and in vitro tests. Plastic dish adherent cells of PC which were Mac-1 positive, large in size and resistant to X-ray, enhanced L1210 growth, whereas non-adherent cells which were Mac-1 negative and small in size, did not. These data suggest that the cells responsible for enhancing activity of tumor progression in the peritoneal cavity were macrophages (M phi).

Animals↗

Induction of calcium influx in immature T lymphocytes by anti-FT-1 monoclonal antibody.

The functional role of FT-1 antigen was investigated by measuring changes in intracellular [Ca2+]i after the addition of anti-FT-1 monoclonal antibody to murine T leukemic cells and embryonic thymocytes. Anti-FT-1 induced a rapid and sustained increase in cytosolic free [Ca2+]i and this effect was completely blocked by EGTA and La3+. These results suggest that FT-1 molecule is functionally associated with a plasma membrane calcium ion channel in embryonic thymocytes.

Animals↗

A synthetic adjuvant effective in inducing antitumor immunity.

Guinea pigs which were injected repeatedly with a mixture of a 3M KCl extract of line 10 tumor and 6-O-(2-tetradecyl-hexadecanoyl)-muramyl-dipeptide (B30-MDP) rejected a tumor graft of line 10. Such an adjuvant effect of B30-MDP was also demonstrated when X-ray-treated line 10 cells were mixed with B30-MDP dissolved in phosphate-buffered saline and inoculated into the animals.

Acetylmuramyl-Alanyl-Isoglutamine↗

Characterization of suppressor T-cells induced with concanavalin A in vivo by cell electrophoresis.

The splenic T-cells of concanavalin A (Con-A)-injected mice suppressed the in vitro Con A-induced splenic blastogenesis of normal mice. We examined electrophoretic mobilities (EPM) and surface markers of Con A-induced suppressor T-cells as a model of suppressor T-cells. The EPM of the suppressor cells with both Thy-1 and gangliotetraosyl-ceramide (asialo GM1) was lower than that of normal T-cells. The ratio of low mobility T-cells (LMT) to high mobility T-cells (HMT) correlated significantly with dose-response and time-course of Con A in the suppressor activity and with the percentages of cells carrying asialo GM1 antigen and receptor for peanut agglutinin. For in vitro induction by Con A, Lyt-2+ cells were reported to have suppressor activity. However, for in vivo induction by Con A, Lyt-2+ cells did not correlate with the suppressor activity in the dose-response and time-course experiments. By separating the Lyt-subsets, it was found that both Lyt-1+2+ and Lyt-1+2- subsets were suppressor cells in the blastogenesis. The suppressor activity of in vivo Con A-induced spleen cells correlated with the LMT/HMT ratio, but not with the analysis of Lyt-phenotype. These results suggested that lymphocytes electrophoresis clearly distinguished Con A-induced suppressor T-cells with low EPM from normal T-cells.

Animals↗

B-cell lymphoma of probable thymic origin: case report.

A case of B-cell lymphoma of probable thymic origin is reported. A 34-year-old woman was found to have an anterior mediastinal tumor in November 1986. The surface lymph nodes were not palpable. A total resection of the tumor mass was performed. The tumor invaded the right pleura, the right lung and the pericardium. Histologically, normal thymus was found at the margin of the tumor tissue. The neoplasm was predominantly composed of large lymphoid cells, separated by rather thick fibrous bands of nodular fashion in some areas. Immunohistochemical staining demonstrated monoclonal cytoplasmic IgG and kappa chains in a small portion of the neoplastic cells in fixed tissue. The cells showed positive staining with cluster of differentiation (CD) 20 (B1) but negative staining with antibodies reactive with T-cells in unfixed tissue. "Malignant lymphoma, diffuse, large cell type (B)" was the diagnosis. The arrangements of immunoglobulin (Ig) and T cell receptor (TCR) beta genes were studied. Clonal rearrangement bands of IgH and Ig kappa genes were observed in the same sizes in both the tumor and the peripheral blood before chemotherapy. The patient received chemotherapy until September 1987, and is in complete remission at present (January 1988). The peripheral blood showed germ line patterns of IgH and Ig kappa genes in complete remission. No rearrangement bands of TCR beta genes were detected throughout. The B-cell lineage was proved both from gene arrangement analysis and with immunohistochemistry.

Adult↗

[Enhancement of antitumor effects by the combination of cytotoxic agents and cytokines].

The characteristics and feasibility of combination therapy of cytotoxic agents and cytokines were discussed from the theoretical as well as experimental basis. The content was divided into two parts depending upon requirements and elements for tumor cells to proliferate. One was concerning the in vitro conditions in which tumor cells were supplied all of them sufficiently. The other was concerning the host conditions in which cells were not necessarily supplied all of them freely and sufficiently. On the basis of characteristic tumor cell and host modifications achieved through receptor binding of cytokines, the combination of cytotoxic agents with cytokines, particularly with interferons, would produced the therapeutic effects that are distinct from those produced by the combination among cytotoxic agents. The clinical and experimental findings were reviewed and summarized along with this proposal.

Antineoplastic Agents↗

Essential requirement of I-A region-identical host bone marrow or bone marrow-derived cells for tumor neutralization by primed L3T4+ T cells.

The antitumor activity of Meth A-hyperimmunized BALB/c mouse spleen cells (Meth A-Im-SPL) was assayed by the Winn test in H-2 incompatible bone marrow chimeras in closed colony CD-1 (nu/nu), inbred DDD/1(nu/nu) (H-2s), or inbred BALB/c(nu/nu) (H-2d) mice as recipients. We found that Meth A-Im-SPL suppressed Meth A growth in the chimera nude mice which were reconstituted with bone marrow cells of the H-2d haplotype (i.e., BALB/c, DBA/2 and B10.D2), but not in the chimeras which were reconstituted with bone marrow cells of the H-2a, H-2b, or H-2k haplotype (i.e., B10.A, B10, and B10.BR). These results suggested that H-2 restriction occurred between Meth A-Im-SPL and bone marrow or bone marrow-derived cells in tumor neutralization. Furthermore, Meth A-Im-SPL did not suppress Meth 1 tumors (antigenically distinct from Meth A tumors) in the presence or absence of mitomycin C-treated Meth A in a Winn assay. These results suggested that there is tumor specificity in the "effector phase" as well as in the "induction phase". The phenotype of the effectors in the Meth A-Im-SPL was Thy-1.2+ and L3T4+, because Meth A-Im-SPL lost their antitumor activity with pretreatment with anti-Thy-1.2 monoclonal antibody (mAb) and complement or anti-L3T4 mAb and complement, but not with anti-Lyt-2.2 mAb and complement or complement alone. Positively purified L3T4+ T cells from Meth A-Im-SPL (Meth A-Im-L3T4), obtained by the panning method, suppressed the tumor growth in the chimera nude mice which were reconstituted with bone marrow cells of B10.KEA2 mice (that were I-A region-identical with Meth A-Im-L3T4 cells but not others in H-2) as well as B10.D2 cells (that were fully identical with Meth A-Im-L3T4 cells in H-2). We conclude that Meth A-Im-SPL (L3T4+) neutralized the tumors in collaboration with I-A region-identical host bone marrow or bone marrow-derived cells, and the neutralization was not accompanied by the "bystander effect."

Animals↗

I-Ad antigen expression of pyran copolymer-induced peritoneal cells in tumor vaccine-primed mice and its association with the host antitumor response.

Mice inoculated IP with L1210 murine leukemia vaccine and subsequently with pyran copolymer-induced macrophages (pyran-M phi) lived for a prolonged time after live L1210 inoculation IP. Pyran-M phi as tentatively identified by anti-AcM.1 monoclonal antibody expressed I-Ad antigen in tumor vaccine-primed recipient mice and contributed to maintaining I-Ad antigen positive (I-Ad+) macrophages at high cell density in the peritoneal cavity of recipient mice. The relevance of these I-Ad+ cells to the host antitumor response was examined by experiments in which I-Ad+ cell density in the peritoneal cavity and host antitumor response behaved in a parallel fashion. Human interferon-alpha A/D, an agent selectively inhibiting Ia antigen expression, and silica, a general antimacrophage agent, strongly suppressed I-Ad antigen expression of peritoneal macrophages of tumor vaccine-primed and pyran-M phi-inoculated mice and, consistently with this, the antitumor response was nullified in these mice. Tumor vaccine-primed mice inoculated with sodium caseinate or thioglycollate-induced peritoneal cells did not survive L1210 inoculation and, in these mice, I-Ad+ peritoneal macrophages were suppressed in number as compared with those of tumor vaccine-primed and pyran-M phi-inoculated mice. These results warrant further study on the contribution of I-Ad+ macrophages to pyran copolymer-induced augmentation of the antitumor response in tumor vaccine-primed mice.

Animals↗

Tumor cell detection method using complement-mediated cytolytic reaction and imaging sensor system.

A novel tumor-detection system consisting of complement-mediated cytolytic reaction and an image processing system was developed for the simple and rapid determination of tumor cells. The present system consists of a CCD image sensor, image memory board, personal computer, and microscope. When monoclonal antibody 3C4, which is specific to the guinea pig hepatoma L-10, was added to cell suspension, only L-10 cytolysis occurred. Cytolysis caused a decrease in brightness of the cells observed by phase-contrast microscopy. The phase contrast image of the cells before cytolysis was converted to a digitalized signal and stored in computer memory. After cytolysis, a brightness threshold above that of lysed cells was subtracted from the digitalized signal and compared to the signal stored before reaction. L-10 cells in mixed cell suspension were determined specifically by the system. Measurement time was only 2 sec and overall time, including reaction time, was approximately 30 min. Since this method does not require a cell washing process, automation of the whole system is possible.

Animals↗

Guanine nucleotide activation of, and competition between, RAS proteins from Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, yeast RAS proteins are potent activators of adenylate cyclase. In the present work we measured the activity of adenylate cyclase in membranes from Saccharomyces cerevisiae which overexpress this enzyme. The response of the enzyme to added RAS2 proteins bound with various guanine nucleotides and their analogs suggests that RAS2 proteins are active in their GTP-bound form and are virtually inactive in their GDP-bound form. Also, active RAS2 protein is not inhibited by inactive RAS2, suggesting that the inactive form does not compete with the active form in binding to its effector.

Adenylyl Cyclases↗

The collaboration of H-2 identical bone marrow cells in in vivo antitumor activity of immune mouse splenocytes.

Antitumor activity of Meth A-immune BALB/c mouse spleen cells (Meth A-Im-SPL) was assayed by a Winn test in CD-1(nu/nu) or BALB/c(nu/nu) chimeric mice which were reconstituted with the bone marrow cells of various strains of mice. It was found that Meth A-Im-SPL (L3T4+ T cells) neutralized the tumor in collaboration with H-2 compatible bone marrow or bone marrow-derived cells.

Animals↗