Biomedical subjects

T Kataoka

Publications and source records attributed to T Kataoka.

At least 181 records · Page 10Linked to original sources

PubMed1990

Up-regulation of transferrin receptor gene expression by granulocyte colony-stimulating factor in human myeloid leukemia cells.

Granulocyte colony-stimulating factor (G-CSF) enhanced surface transferrin receptor (TfR) expression in two human myeloid leukemia cell lines, NKM-1 and NOMO-1, which possess G-CSF receptors. Radioligand-binding assay revealed that 10 ng/ml G-CSF significantly increased TfR to 186 +/- 20 and 276 +/- 38% of control for NKM-1 cells and NOMO-1 cells, respectively, in a 24-h culture. Scatchard analysis showed the increase of transferrin (Tf)-binding sites but no change in the receptor affinity. The enhanced TfR expression was not mediated either by the kinetic change of receptor cycling or by cellular iron content. Immunoprecipitation with anti-TfR antibody was used, and the increased biosynthesis of the receptor was demonstrated in G-CSF-stimulated cells. Northern blot analysis showed a 2- to 3-fold increase of TfR mRNA of NKM-1 cells cultured in medium containing Tf and G-CSF, whereas the mRNA declined without G-CSF. The effect of G-CSF on the TfR mRNA was observed within 2 h, which preceded the increase of surface TfR and the transition to the S phase of the cell cycle. G-CSF also potentiated TfR expression in freshly obtained myeloid leukemia cells. The present study shows up-regulation of TfR expression by G-CSF in myeloid leukemia cells and provides evidence that the regulation is mediated by controlling the steady-state level of the mRNA.

Biological Transport↗

PubMed1990

A novel human myeloid leukemia cell line, NKM-1, coexpressing granulocyte colony-stimulating factor receptors and macrophage colony-stimulating factor receptors.

A novel human myeloid leukemia cell line, NKM-1, was established from a patient with acute myeloid leukemia (FAB classification M2). The cells were positive for myeloperoxidase staining and cluster of differentiation 15 cell surface antigen. Radiolabeled recombinant human granulocyte (G) colony-stimulating factor (CSF) was used, and 60 specific binding sites/cell with a Kd 100 pmol/liter were demonstrated on the cell surface. 125I-G-CSF binding was not inhibited by interleukin-3, granulocyte-macrophage CSF, or macrophage (M) CSF. NKM-1 cells also expressed M-CSF receptors detected by c-fms mRNA expression. In concordance with the receptor expression, NKM-1 cells proliferated in response to exogenous G-CSF or M-CSF in a dose-dependent manner (0.1-100 ng/ml), while interleukin-3 or granulocyte-macrophage CSF had no effect. Colony-forming capacity of NKM-1 cells in semisolid agar was also enhanced with the addition of 10 ng/ml of G-CSF or M-CSF but decreased at higher concentrations. During CSF stimulation, no remarkable changes were observed morphologically and phenotypically. The stimulatory effect of G-CSF and M-CSF on the cell growth was additive. Neither G-CSF-binding capacity nor c-fms mRNA expression was altered by pretreatment with M-CSF or G-CSF, respectively. This cell line may provide a useful in vitro model for the study of CSF roles in myeloid leukemia cell proliferation.

Adult↗

PubMed1990

Essential role of nitric oxide in descending inhibition in the rat proximal colon.

Possible mediators of descending inhibition in the rat proximal colon were studied. Localized distension with a small balloon caused relaxation of the circular muscle on the anal side of the distended region. This relaxation was still observed after the colonic segment had been desensitized to ATP, neurotensin and vasoactive intestinal peptide, so these compounds seem unlikely to mediate descending inhibition. Nitro-arginine inhibited the relaxation induced by the distension, and L-arginine counteracted the effect of nitro-arginine. Nitric oxide, isoamylnitrate and sodium nitroprusside caused relaxation. These results strongly suggest an essential role of nitric oxide in descending relaxation in the rat proximal colon.

Adenosine Triphosphate↗

PubMed1990

Cloning and characterization of CAP, the S. cerevisiae gene encoding the 70 kd adenylyl cyclase-associated protein.

Adenylyl cyclase from S. cerevisiae contains at least two subunits, a 200 kd catalytic subunit and a subunit with an apparent molecular size of 70 kd, which we now call CAP (cyclase-associated protein). We cloned a cDNA encoding CAP by screening a yeast cDNA expression library in E. coli with antisera raised against the purified protein. The cDNA contained an open reading frame capable of encoding a 526 amino acid protein that is not homologous to any sequences in the current data bases. Adenylyl cyclase activity in membranes from cells that lacked CAP was not stimulated by RAS2 proteins in vitro. These results suggest that CAP is required for at least some aspects of the RAS-responsive signaling system. Mutants lacking CAP had four additional phenotypes that appear to be unrelated to effects of the RAS/adenylyl cyclase pathway: the inability to grow on rich medium (YPD), temperature sensitivity on minimal medium, sensitivity to nitrogen starvation, and a swollen cell morphology.

Adenylyl Cyclases↗

PubMed1990

Experimental cancer cachexia induced by transplantable colon 26 adenocarcinoma in mice.

The present study investigates a tumor model for cachectic mice. Among various murine transplantable tumors, used for assessing cytostatics, we identified colon 26 adenocarcinoma (colon 26) as capable of causing cachexia. Fifteen days after inoculation, the tumor grew to about 6% of the body weight causing substantial carcass weight loss of 3.4 g (14.5% of the carcass weight). When the tumor size was 2.7 g at 3 weeks after the inoculation, the carcass weight was 12 g less than the age-matched control. The tumor continued to grow while the mice maintained this weight, surviving for an average of 45 days. This extensive weight loss was essentially the wasting of adipose and muscle tissues. Hypoglycemia and hypercorticism occurred during the time of the weight loss. In addition, the colon 26 caused disorders of hepatic functions: the concentration of acute phase proteins in serum increased; the number of hepatic glucocorticoid-cytosol receptors decreased; and activities of hepatic catalase and drug-metabolizing enzymes decreased. On the other hand, noncachectic mice with Meth A fibrosarcoma gained weight, which was somewhat less than the control, and had neither hypoglycemia nor hypercorticism, although some mild disorders of hepatic functions were found. Mice bearing colon 26 is an appropriate model for elucidating the mechanism that causes cachexia.

Adenocarcinoma↗

PubMed1990

Periodic formation of the oriC complex of Escherichia coli.

We examined formation of an oriC-membrane complex through the chromosome replication cycle by dot-blot hybridization using an oriC plasmid as a probe. In a wild-type culture synchronized for chromosome replication, oriC complex formation was observed periodically and transiently corresponding to the replication initiation event. Prior to initiation of replication the oriC complex was recovered in the outer membrane fraction as well as at the time of initiation of replication. Moreover, periodic formation of the oriC complex was observed even when further initiation of replication was suppressed by culturing an initiation ts mutant at the restrictive temperature. Similar periodic formation of the oriC complex was also observed when DNA elongation was inhibited by addition of nalidixic acid to the culture. However, the second periodic peak did not appear when rifampicin or chloramphenicol was added. Cells which formed the oriC complex at the restrictive temperature could immediately initiate chromosome replication when the cells were transferred to the permissive temperature. We conclude that the oriC region of Escherichia coli forms a specific complex periodically just before and at the time of initiation of chromosome replication and that oriC complex formation is a prerequisite for initiation of chromosome replication.

Bacterial Outer Membrane Proteins↗

PubMed1990

Lymphocyte electrophoresis as an indicator of modulation of concanavalin A-induced suppressor T-cells in vivo by anti-cancer drugs.

We have previously reported that concanavalin A (Con A)-induced suppressor T-cells in vivo are located in the lower electrophoretic mobility (EPM) zone as judged by the ratio of low mobility T-cells to high mobility T-cells (LMT/HMT ratio) in terms of lymphocyte electrophoresis, and that the administration of 5-fluorouracil (5-FU) eliminates their suppressor activity as assayed by Con A-induced lymphocyte blastogenesis in vitro. The current study was undertaken to clarify the relation between changes in EPM and suppressor activity of Con A-induced suppressor T-cells by the administration of antitumor drugs such as cyclophosphamide (CY) and 5-FU when assayed by production of anti-sheep red blood cell antibody in vitro. The pretreatment with 5-FU, but not CY, abrogated the suppressor activity of Con A-induced T-cells followed by restoration of the LMT/HMT ratio of Con A-induced T-cells to that of normal T-cells. These finding suggest that lymphocyte electrophoresis can be applied to an assay for screening immunomodulating agents in Con A-induced suppressor T-cells.

Animals↗

PubMed1990

Development of a new type of influenza subunit vaccine made by muramyldipeptide-liposome: enhancement of humoral and cellular immune responses.

The muramyldipeptide (MDP), [6-O-(2-tetradecyl-hexa-decanoyl)-N-acetylmuramyl-L-isoglutamine] can be incorporated into liposomes with haemagglutinin and neuraminidase subunits were attached to the inner and outer surfaces of lamellar structures of the liposomes, probably through their hydrophobic ends. The addition of cholesterol resulted in much more stable liposomes, which were similar in size and shape to native influenza virus particles. These liposomes enhanced the immunogenicity of haemagglutinin in mice, such that the levels of antibody induced were about 16-fold higher than those of subunit haemagglutinin vaccine alone. Results of proliferation tests with spleen cells from mice and guinea-pigs were consistent with the immunopotentiation of haemagglutinin by liposomes. In addition, the higher antibody levels produced in mice, immunized with the haemagglutinin and MDP-containing liposomes (MDP-virosomes), were maintained for at least 6 months. Enhancement of the cellular immune response, measured by delayed type hypersensitivity reactions, was also observed in the guinea-pigs immunized with MDP-virosome vaccine. Preliminary tests with splenocytes from mice immunized with different vaccines also indicated that the MDP-virosome vaccine induced cytotoxic T-cell activity in these mice. This study revealed that the formation of liposomes with muramyldipeptide enhanced the level and persistence of circulating antibody, and enhanced cellular immunity in guinea-pigs and mice.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1990

Leucine-rich repeats and carboxyl terminus are required for interaction of yeast adenylate cyclase with RAS proteins.

A Saccharomyces cerevisiae gene encoding adenylate cyclase has been analyzed by deletion and insertion mutagenesis to localize regions required for activation by the Sa. cerevisiae RAS2 protein. The NH2-terminal 657 amino acids were found to be dispensable for the activation. However, almost all 2-amino acid insertions in the middle 600 residues comprising leucine-rich repeats and deletions in the COOH-terminal 66 residues completely abolished activation by the RAS2 protein, whereas insertion mutations in the other regions generally had no effect. Chimeric adenylate cyclases were constructed by swapping the upstream and downstream portions surrounding the catalytic domains between the Sa. cerevisiae and Schizosaccharomyces pombe adenylate cyclases and examined for activation by the RAS2 protein. We found that the fusion containing both the NH2-terminal 1600 residues and the COOH-terminal 66 residues of the Sa. cerevisiae cyclase rendered the catalytic domain of the Sc. pombe cyclase, which otherwise did not respond to RAS proteins, activatable by the RAS2 protein. Thus the leucine-rich repeats and the COOH terminus of the Sa. cerevisiae adenylate cyclase appear to be required for interaction with RAS proteins.

Adenylyl Cyclases↗

PubMed1990

Antitumor activity of T cells in lymphoid organs induced by interferon in tumor-bearing mice.

Administration of human hybrid interferon-alpha A/D (IFN) for 5 consecutive days induced antitumor activity in spleen of Meth A fibrosarcoma-bearing mice 9-10 days after cessation of IFN administration. Antitumor activity assayed by the in vivo neutralization test was found in the spleen of responding mice but not in that of progressive mice. This activity was T-cell-dependent and tumor-selective. However, tumor-neutralizing activity was not found in spleen recovered as early as 3 days after cessation of IFN administration when many tumor cells are still surviving in tumor nodules and being attacked by the host. Instead, T-cell-dependent and tumor-selective tumor-neutralizing activity was found in the lymph node of tumor-bearing mice at this early stage. Furthermore, the tumor-neutralizing activity was already detected in the lymph nodes during the course of IFN administration, although there was no difference in the cell composition of the lymph nodes of IFN- and placebo-administered mice. Since IFN-alpha is apparently not a direct modifier of T cells, these results indicate that IFN probably did not directly increase the number of antitumor T cells but instead modified the host-tumor interaction in such a way that, as an early event, the enhanced T-cell response to tumor cells occurred, resulting in an increase in the antitumor T-cell population in lymph nodes. We supposed that, as the tumor regressed, these antitumor T cells would eventually leave the lymph node and migrate to the spleen.

Animals↗

PubMed1990

Production of antitumor mononuclear blood cells in tumor-bearing mice by interferon-alpha A/D therapy.

Administration of human interferon-alpha A/D (IFN-alpha A/D) to Meth A fibrosarcoma-bearing mice produced mononuclear blood cells with antiproliferation activity that were able to suppress Meth A growth in vitro. Their production depended on IFN doses and administration intervals. They were short-lived since antiproliferation activity was not detectable in mononuclear cells 2 days after cessation of IFN administration, although it was detectable as long as IFN administration continued. A similar production of antiproliferative mononuclear blood cells by IFN was achieved in tumor-free as well as in tumor-bearing mice, indicating no deleterious effect of the growing tumor on the production of these cells. IFN-induced antiproliferation activity was not tumor-specific since mononuclear blood cells of IFN-administered mice bearing either Meth A and Meth 1, another antigenically distinct fibrosarcoma, suppressed the in vitro growth of both Meth A and Meth 1 cells. T cells were not involved in the in vivo production of antiproliferative mononuclear blood cells by IFN therapy because the cells with this activity were produced in vivo in Meth A-bearing athymic mice and also in Meth A-bearing mice with reduced T-cell populations by the treatment with alpha mouse thymocyte globulin. T cells were not involved in their antiproliferation activity either, since the in vitro T-cell depletion of mononuclear cells did not diminish this antiproliferation activity. Because mononuclear cells surviving the in vitro T cell depletion were positive for AcM.1 (an epitope of activated macrophage) and also because the alpha Mac-1 antibody completely abolished their in vitro antiproliferation activity, this led us to conclude that it was activated monocytes in blood that were produced by IFN in a T-cell-independent fashion and that these monocytes were the cells responsible for the observed in vitro antiproliferation activity.

Animals↗

PubMed1990

Antitumor activity of host T and non-T cells recovered from tumor nodules after interferon therapy.

We examined the modification of host T cells of tumor nodules by interferon (IFN) therapy in mouse models. The host cells were recovered from regressing tumor nodules of mice at Day 13 after intradermal tumor inoculation at Day 0 and administration of 5 x 10(5) U/mouse/day IFN at Day 6 to Day 10. These host cells neutralized in vivo Meth A growth in a dose-dependent fashion. In vitro treatment of these cells with anti-Thy 1.2 monoclonal antibody and rabbit sera as a source of complement abrogated their tumor-neutralizing activity, but only partially, indicating that both T cells and non-T cells were involved in tumor neutralization. The finding that host cells from regressing tumor nodules of either Meth A or Meth 1, an antigenically distinct fibrosarcoma, neutralized both Meth A and Meth 1 tumors without much selectivity was consistent with possible non-T cell involvement. Most of these characteristics of host cells of regressing nodules of IFN-administered mice were also noted with host cells of progressing nodules of placebo-administered mice and there was no significant difference in neutralizing activity qualitatively or quantitatively between the two sources of host cells. There was no significant difference in host T and B cell numbers and compositions of regressing and progressing nodules either. These essentially negative findings raise the possibility, among others, that the primary target host cells to be modified by IFN were not T cells, although the therapeutic effect of IFN was dependent on the host T cells.

Animals↗

PubMed1990

Differences in control of descending inhibition in the proximal and distal regions of rat colon.

1. Descending inhibition in the proximal and distal portions of rat colon was studied separately, in vitro. 2. In the proximal colon, localized distension with a small balloon caused three types of response (contraction; relaxation; relaxation, then contraction) of the circular muscle on the anal side of the distended region. 3. Distension caused descending relaxation of circular muscle in all segments of the proximal colon, although for this prostaglandin F2 alpha (PGF 2 alpha) was necessary in some segments to increase muscle tone. 4. Atropine and guanethidine did not inhibit this descending relaxation, but tetrodotoxin did. 5. Hexamethonium inhibited the descending relaxation in 14 of 17 preparations of proximal colon tested, but not in the others. 6. In the distal colon, distension consistently caused an increase in the tone of the circular muscles. Descending relaxation was observed only after development of higher tone. Atropine and guanethidine did not inhibit the relaxation, but tetrodotoxin did. 7. Hexamethonium did not inhibit the descending relaxation in most of the preparations of distal colon examined. 8. AF64A, an inhibitor of choline uptake, inhibited the response mediated by cholinergic neurons in vitro to electrical transmural stimulation of the longitudinal muscle of proximal colon. 9. Treatment of colonic preparations with AF64A in vitro resulted in inhibition of descending relaxation in those of proximal, but not those of distal, colon. 10. The participation of intrinsic cholinergic neurones in the descending neuronal pathway is strongly suggested by the results in the proximal colon, but less so in the distal colon. 11. The tone and spontaneous contractile activity of colonic circular muscles are discussed in relation to their neuronal control.

Animals↗

PubMed1990

Selective immunosuppression of prodigiosin 25-C and FK506 in the murine immune system.

The immunosuppressive effects of prodigiosin 25-C were studied in comparison with FK506. Both prodigiosin 25-C and FK506 suppressed T cell proliferation in response to concanavalin A (con A) or phytohemagglutinin (PHA) more significantly than that to lipopolysaccharide. However, prodigiosin 25-C inhibited con A-mediated mitogenic response more strongly than PHA-mediated one. FK506 showed no selectivity among those responses. In addition, when higher concentration of con A was used an inhibitory effect of prodigiosin 25-C became more evident whereas that of FK506 became less evident. Furthermore, prodigiosin 25-C affected neither interleukin-2 (IL-2) production nor IL-2 receptor (IL-2R) and transferrin receptor (TF-R) expression in vitro, though FK506 extensively inhibited IL-2 production and significantly suppressed IL-2R and TF-R expression. When comparing the effects of prodigiosin 25-C and FK506 in vivo by injecting antigens of different nature to a mouse, prodigiosin 25-C selectively inhibited cytotoxic T lymphocyte (CTL) activity induced by an allogenic mastocytoma, P815, without affecting production of antibody against a thymus dependent (TD) antigen, sheep red blood cell (SRBC). On the contrary, FK506 significantly inhibited both CTL induction and the antibody production. When Brucella abortus, a thymus independent (TI) antigen, and SRBC were simultaneously challenged to a mouse, neither prodigiosin 25-C nor FK506 affected antibody production against the TI antigen while the effect on the TD antigen were the same as described above. The present results revealed the unique immunosuppressive property of prodigiosin 25-C which was different from that of FK506.

Animals↗

PubMed1990

Immunotherapeutic potential in guinea-pig tumor model of deoxyribonucleic acid from Mycobacterium bovis BCG complexed with poly-L-lysine and carboxymethylcellulose.

In vivo antitumor activity of a deoxyribonucleic acid fraction obtained from Mycobacterium bovis BCG (named MY-1) increased when it was complexed with poly-L-lysine (poly LL) solubilized by addition of carboxymethylcellulose (CMC). The complex of MY-1 and poly LL/CMC induced interferon in vivo at a low dose of MY-1 which alone exerted no IFN induction. With Line 10 hepatoma (L10) which is syngeneic with strain 2 guinea pigs, it was demonstrated that repeated intralesional injections of the complex resulted in delay of tumor growth and complete cure of animals from L10 tumor inoculated. Similar treatment of the animals with the same amount of MY-1 or poly LL/CMC alone had little therapeutic effect on the tumor growth.

Animals↗

PubMed1990

[Modification of peripheral blood monocytes and T lymphocytes of lymphoid organs by interferon-alpha therapy].

We examined interferon (IFN)-alpha therapy in animal models from the immunological aspects. Long after the cessation of successful IFN administration there found a strong tumor neutralizing activity of spleen T cells in the curing mice. However, this activity was not detectable right after the cessation of IFN administration. Instead, in this early stage, a strong tumor neutralizing activity was found in the lymph nodes of IFN-administered mice. This does not necessarily indicate that the primary modifying target of IFN was T cells since IFN is not capable of directly activating T cells. Further experimentation showed that IFN administration resulted in the very fast production of antitumor monocytes in peripheral blood. Again, this may not be a primary modifying target of IFN since IFN is a very poor activator of monocytes and macrophages and sometimes a very strong nullifier of activation of these cells. Based on these results and those reported in the literatures, it was discussed what would be a real modifying target of IFN in association with the therapeutic effect.

Animals↗

PubMed1990

[Prostaglandin-E2 (PGE2) and interleukin-1 (IL-1) production from plastic-adherent peripheral blood mononuclear cells, and serum and urinary glucocorticoid levels in cancer patients treated with systemic chemotherapy--with special reference to circadian rhythm of serum cortisol levels in cancer].

Prostaglandin-E2 (PGE2) and interleukin-1 (IL-1) production from plastic-adherent peripheral blood mononuclear cells stimulated in vitro by bacterial lipopolysaccharide, serum and urinary glucocorticoid levels and the circadian rhythm of serum cortisol levels were studied for better understanding of the immunological and physiological changes produced by systemic chemotherapy in cancer patients. In one responded patient out of four, PGE2 production decreased and IL-1 production increased, whereas the serum cortisol level decreased and the urinary 17-KS excretion level increased. The circadian rhythm of the serum cortisol level was evaluated three times a day, at 7 A.M., 2 P.M. and 10 P.M. Healthy volunteers showed a peak level at 7 A.M. which decreased gradually towards evening and reached to the lowest level at 10 P.M. In contrast, cancer patients showed three additional patterns. These patterns were classified as follows, Type N showed a maximal level at 7 A.M. and minimal level at 10 P.M. as same as in healthy subjects. Type V showed a minimal level at 2 P.M. while type A showed a maximal level at this time. In type F the serum cortisol level was no greater than 1.0 micrograms/dl at any of the three time points. We examined circadian rhythm in four cancer patients treated with systemic chemotherapy. In one PR case, the circadian rhythm shifted from type V to N after the first course of therapy, then changed to type F after subsequent and another courses of the therapy. In another PR case, type N persisted during and after therapy. One MR case shifted from type A to type N. In contrast, one PD case shifted from type N to A. There results suggest that normalization of the circadian rhythm of serum cortisol was associated with the improvement in host body condition achieved by chemotherapy and that systemic chemotherapy modified the immunological and physiological state of cancer patients, as defined above. This may eventually be beneficial for patients.

Adult↗

PubMed1990

[Diagnosis of cancer using lymphocyte electrophoresis (3): Electrophoretic mobility, interleukin 1 and prostaglandin E2 productions of monocytes in peripheral blood of cancer patients].

The S/F ratio of slow electrophoretic mobility cells (less than 0.95 micron/sec/V/cm) to fast mobility cells (greater than or equal to 0.95) increased significantly in the peripheral blood mononuclear cells of cancer patients. Since one of slow mobility cells was mainly composed of monocytes, the relationship between the mobility and the functions of monocytes in the peripheral blood of patients with cancer was examined. The cancer patients (total 27) consisted of 12 patients with rectum, 7 with colon, 3 with stomach, one with ovary and 4 with recurrent cancers and of 3 with stage 1, 11 with stage 2, 3 with stage 3 and 6 with stage 4 + 5. We determined the releases of interleukin 1 (IL-1) and prostaglandin E2 (PGE2) from monocytes, which were stimulated with lipopolysaccharide, as an index for the function of monocytes. The mobility of monocytes and productions of IL-1 and PGE2 from monocytes decreased with the stage of cancer patients, indicating a decreased function of monocytes in the patients. These findings suggest that S/F ratio of the peripheral blood mononuclear cells and mobility, IL-1 and PGE2 productions of monocytes are a good index for the judgement of treatment efficacy of cancer.

Colorectal Neoplasms↗