Search PubMed⌕ Search

Biomedical subjects

T Kataoka

Publications and source records attributed to T Kataoka.

At least 127 records · Page 7Linked to original sources
PubMed1995

Prodigiosin 25-C uncouples vacuolar type H(+)-ATPase, inhibits vacuolar acidification and affects glycoprotein processing.

Prodigiosin 25-C inhibited the accumulation of 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine and acridine orange in the acidic compartments of baby hamster kidney cells with little perturbation of cellular ATP levels. In rat liver lysosomes, prodigiosin 25-C inhibited the proton pump activity with an IC50 of approximately 30 nM, but did not affect ATPase activity up to 1 microM. It also delayed the transport of vesicular stomatitis virus G protein and induced a drastic swelling of Golgi apparatus and mitochondria. These results indicate that prodigiosin 25-C raises the pH of acidic compartments through inhibition of the proton pump activity of vacuolar type H(+)-ATPase, thereby causing the functional and morphological changes to the Golgi apparatus.

Adenosine Triphosphate↗
PubMed1995

Protein kinase Byr2 is a target of Ras1 in the fission yeast Schizosaccharomyces pombe.

Conservation of the structure and function of Ras proteins has been observed in a variety of eukaryotic organisms. However, the nature of their downstream effectors appears to be quite divergent; adenylyl cyclase and a protein kinase Raf-1, which do not share any structural homology with each other, are effectors of Ras in the budding yeast and in higher organisms, respectively. We show here that a protein kinase Byr2, which has been known to act downstream of Ras1 in a mating pheromone signal transduction system of Schizosaccharomyces pombe, binds directly to Ras proteins in a GTP-dependent manner. The region of Byr2 responsible for the Ras binding was mapped by a gene deletion analysis to its N-terminal segment of 206 amino acid residues, which does not possess any significant homology with the other effectors of Ras. The affinity of the Byr2 N terminus for Saccharomyces cerevisiae Ras2 was determined by measuring its activity to competitively inhibit Ras-dependent adenylyl cyclase activity and found to be comparable with those of yeast adenylyl cyclase and human Raf-1, with a dissociation constant (Kd) of about 1 nM. Furthermore, Byr2 inhibited a Ras GTPase-activating activity of Ira2, a S. cerevisiae homologue of neurofibromin. These results indicate that Byr2 is an immediate downstream target of Ras1 in S. pombe.

Adenylyl Cyclases↗
PubMed1995

Opioid receptor interaction and adenylyl cyclase inhibition of dihydroetorphine: direct comparison with etorphine.

To find out the reason of weak addiction property of dihydroetorphine, we compared the affinities of dihydroetorphine to the type selective opioid receptor and inhibition effect on the adenylyl cyclase activity with those of etorphine. Dihydroetorphine and etorphine have almost the same binding affinities to all types (mu, delta, and kappa) of opioid receptors and antagonist binding sites, and have similar inhibition activities to forskolin stimulated adenylyl cyclase. However, dihydroetorphine showed significantly smaller value of DTNB-index compared with that of etorphine. This differentiation may explain partly the high analgesic with low dependence properties of dihydroetorphine.

Adenylyl Cyclase Inhibitors↗
PubMed1995

In vitro and in vivo antitumor activity of the interferon inducer bropirimine.

In vivo and in vitro antitumor effects of an interferon (IFN)-alpha inducer, bropirimine (2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone), were examined in the murine tumor system. The antitumor effects were studied in Meth A cells, which were the most sensitive to bropirimine in the murine cell lines tested. The direct inhibitory activity of the drug was not reduced when Meth A cells were incubated with bropirimine and anti-IFNs, indicating that the inhibition is not due to autocrine IFN induction from tumor cells. The drug partially inhibited the uptake of [3H]thymidine, [3H]uridine and [3H]leucine. Cell cycle analysis with flow cytometry showed that the drug decreased G0/G1 phase and increased G2/M phase Meth A cells. The drug administered i.p. exhibited a remarkable antitumor effect against Meth A cells which were implanted i.p. These results suggested that the drug induced the in vivo antitumor effect by its direct antitumor activity.

Animals↗
PubMed1995

Prodigiosin 25-C suppression of cytotoxic T cells in vitro and in vivo similar to that of concanamycin B, a specific inhibitor of vacuolar type H(+)-ATPase.

The effects of prodigiosin 25-C (PrG) which preferentially suppresses cytotoxic T cells (CTL), was examined in comparison with concanamycin B (CMB), a specific inhibitor of vacuolar type H(+)-ATPase (V-ATPase). PrG and CMB directly inhibited the cytotoxic function of CTL and neutralized acidic organelles of CTL in vitro. In addition, PrG or CMB was injected in C57BL/6 mice after immunization with an allogeneic mastocytoma, P815. PrG and CMB inhibited the killing activity of CTL against the tumor and reduced the population of CD8+ cells without affecting CD4+ and B220+ populations in the spleen. PrG and CMB had only a negligible effect on antibody production induced by sheep red blood cells (SRBC) and mitogenic responses of lymphocytes. These results suggest that PrG and CMB have similar immunosuppressive properties at least through their inhibitory effects on acidification of intracellular organelles required for the effective function of CTL.

Adenosine Triphosphatases↗
PubMed1995

1'-Acetoxychavicol acetate as an inhibitor of phagocytosis of macrophages.

We screened extracts of edible plants for inhibitors of phagocytosis by peritoneal exudate macrophages. 1'-Acetoxychavicol acetate was isolated from the ethyl acetate extract of Languas galanga, and this compound strongly inhibited phagocytosis at an IC50 value of 1.2 microM with negligible effects on pinocytosis and cell viability. Target(s) of 1'-acetoxychavicol acetate was suggested to be downstream of the signal transduction pathway that is mediated by protein kinase C.

Animals↗
PubMed1995

Prodigiosin 25-C perturbs permeation of acetate in a cultured cell line.

Prodigiosin 25-C had little effect on DNA, RNA, and protein synthesis, and cellular ATP content, but the drug markedly inhibited the incorporation of acetate into lipid fractions. Under the same conditions, the incorporation of other lipid precursors including glycerol, mevalonate, palmitate, and oleate was not affected. A decrease in the incorporation of acetate was not due to the inhibition of fatty acid biosynthesis, because prodigiosin 25-C did not affect the activity of acetyl-CoA synthetase, acetyl-CoA carboxylase or fatty acid synthase in cell-free assay systems prepared from rat liver cytosol. In contrast, prodigiosin 25-C strongly inhibited the rapid uptake of acetate into acid-soluble fraction in intact cells. The results suggest that prodigiosin 25-C specifically perturbs the permeation of acetate through plasma membranes.

Acetate-CoA Ligase↗
PubMed1995

Costunolide and dehydrocostus lactone as inhibitors of killing function of cytotoxic T lymphocytes.

Costunolide and dehydrocostus lactone were isolated from an extract of mokko (Saussurea lappa Clarke) as inhibitors of killing activity of cytotoxic T lymphocytes (CTL). Mokko lactone was also isolated as an inactive compound from the extract. The structure-activity relationship indicated that alpha-methylene-gamma-butyrolactone is required for the inhibitory effect. Costunolide markedly inhibited the granule exocytosis and the production of inositol phosphates in response to anti-CD3 monoclonal antibody (mAb) stimulation at a concentration that did not affect the binding of anti-CD3 mAb. Tyrosine phosphorylation induced by crosslinking of CD3 molecules was significantly inhibited by costunolide in a dose-dependent manner. These results suggest that costunolide inhibits the killing activity of CTL through preventing the increase in tyrosine phosphorylation in response to the crosslinking of T-cell receptors.

4-Butyrolactone↗
PubMed1995

Establishment and characterization of a novel cell line, TK-6, derived from T cell blast crisis of chronic myelogenous leukemia, with the secretion of parathyroid hormone-related protein.

We established a novel T cell line, designated TK-6, from a patient with T cell lineage blast crisis of chronic myelogenous leukemia (CML) complicated by hypercalcemia. A surface marker study showed T cell phenotype, cluster designation (CD)4, CD5 and CD7. Light and electron microscopic examination revealed myeloperoxidase (MPO)-negative, however, ultrastructural examination under certain specific conditions demonstrated that some cells were MPO-positive. The TK-6 cell karyotype carried a t(9;22)(q34;q11) and additional chromosome aberrations, including a deletion of the long arm of chromosome 6 and the abnormality of chromosome 7. Southern blot analysis showed rearrangement of the T cell receptor beta-chain (TCR beta) gene and the major breakpoint cluster region (bcr) gene. Northern blot analysis detected the expression of the parathyroid hormone-related protein (PTHrP) gene, however, the proviral genome of human T cell leukemia virus type I (HTLV-I) was negative. This cell line will provide a valuable resource for the analysis of the relationship between T cell lineage crisis and myeloid differentiation and for the analysis of humoral hypercalcemia of malignancy (HHM) or leukemia.

Adult↗
PubMed1995

Cardiorespiratory responses during exercise in competitive in-line skaters.

This study describes the cardiorespiratory responses of 12 male (age = 30 +/- 6 yr) competitive in-line skaters during peak and submaximal skating. We hypothesized that velocities of 22.5 and 27.4 km.h-1 would elicit heart rate (HR) and oxygen consumption (VO2) responses consistent with the American College of Sports Medicine's guidelines for developing cardiorespiratory fitness. Using a 644-m indoor cement course, subjects completed 10 trials comprised of various velocities, stroke frequencies, and body positions. At 22.5 km.h-1, HR and VO2 were 74 and 51% of peak, respectively. At 27.4 km.hr-1, HR and VO2 were 85 and 72% of peak, respectively. When compared to the College's guidelines, regression analysis revealed a leftward shift in the VO2-HR relationship, evidenced by a disproportionately higher HR at a VO2 approximating 60 vs 80% of peak. At 22.5 km.h-1 our skaters self-selected a stroke frequency which resulted in less of an increase in both HR and VO2, when compared to the imposed stroke frequencies of 50 min-1 and 70 min-1. Also, skating at 27.4 km.h-1 in the bent vs upright position resulted in less of an increase in HR and VO2. Competitive in-line skaters are capable of safely skating at velocities sufficient to stimulate an increase in cardiorespiratory fitness. These athletes select a stroke frequency and utilize a body position which results in favorable HR and VO2 responses.

Adult↗
PubMed1994

Acidification is essential for maintaining the structure and function of lytic granules of CTL. Effect of concanamycin A, an inhibitor of vacuolar type H(+)-ATPase, on CTL-mediated cytotoxicity.

An inhibitor of vacuolar type H(+)-ATPase, concanamycin A (CMA), inhibited the specific cytolytic activity of a CD8+ CTL clone, OE4. The inhibitory effect was observed when the effector cells, and not the target cells, were pretreated with CMA. CMA did not seem to inhibit early events, inasmuch as effector/target conjugate formation remained unaffected. Although CMA treatment of OE4 resulted in a slight decrease in the efficiency of granule exocytosis in response to anti-CD3 stimulation, the most prominent effect was a marked reduction of perforin activity and DNA degradation activity in lytic granules. Western blotting analysis indicated a drastic decrease in the amount of perforin in CMA-treated cells. Fluorescent microscopic observation of OE4 stained with acridine orange indicated that CMA raised the pH of the lytic granules. Under transmission electron microscopy, striking morphologic changes in cytoplasmic granular structures were observed after CMA treatment of OE4. The lytic granules of OE4 had homogeneously stained large cores and numerous small vesicles that filled peripheral areas. In contrast, the lytic granules of CMA-treated OE4 showed irregular shapes with no small vesicles, but with cores that became rough and loose. Vacuoles with no structure in them were seen occasionally. These results suggest that acidification through vacuolar type H(+)-ATPase is essential to maintain the structure and function of lytic granules.

Acid-Base Equilibrium↗
PubMed1994

Quantitative analysis of mutually competitive binding of human Raf-1 and yeast adenylyl cyclase to Ras proteins.

Ras proteins appear to have two distinct downstream effectors, adenylyl cyclase in Saccharomyces cerevisiae and a product of raf-1 protooncogene in higher organisms. We found that in vitro activation of adenylyl cyclase by yeast Ras2 and human H-Ras proteins is subject to competitive inhibition by its leucine-rich repeats domain and by the N-terminal regulatory domain of human Raf-1 protein. Kinetic analyses of the inhibition patterns enabled us to determine exact dissociation constants (Kd) of the two polypeptides for Ras2 and H-Ras. The leucine-rich repeats domain bound to the posttranslationally modified Ras2 with the Kd of approximately 13 nM, which was close to the value (7 nM) of the whole adenylyl cyclase. The Kd of Raf-1 for the modified H-Ras, 3.5 nM, was significantly lower than that for Ras2, 24 nM, whereas adenylyl cyclase bound preferentially to Ras2. Similar inhibition was also observed in vivo by suppression of RAS2Val-19-dependent heat shock sensitivity and of Ras-dependent cAMP response to glucose upon overexpression of Raf-1 in yeast. These results indicate that the leucine-rich repeats domain contains the Ras protein-binding site and that Raf-1 and adenylyl cyclase, sharing no structural homology with each other, bind to a similar, if not identical, region of Ras with comparable affinities.

Adenylyl Cyclase Inhibitors↗
PubMed1994

Cardiovascular responses of cardiac transplant patients to arm and leg exercise.

This investigation compares the cardiovascular responses of normal (n = 10) and cardiac transplant (n = 14) subjects to peak arm and leg exercise. It also tests the hypothesis that the higher heart rate (fc) in normal subjects during light (30 W) submaximal arm versus leg exercise is due to cardiac innervation. In cardiac transplant patients, power output, oxygen consumption (VO2), fc and rate pressure product were 54%, 28%, 7%, and 8% lower during peak arm than leg exercise, respectively. In normal subjects, power output, VO2, fc and rate pressure product were 61%, 33%, 8%, and 11% lower during peak arm than leg exercise, respectively. In cardiac transplant patients there was no significant difference in absolute fc during submaximal arm and leg exercise. In normal subjects, absolute fc during arm and leg exercise was [mean (SD)] 97 (4) beats.min-1 and 92 (4) beats.min-1, respectively (P = 0.07). Plasma noradrenaline was increased more during arm than leg exercise in both cardiac transplant and normal subjects. Maximal leg testing is useful when determining the capacity of cardiac transplant patients to perform arm work. The higher absolute fc reported by other investigators for normal subjects during submaximal arm versus leg exercise may be mediated by cardiac innervation.

Arm↗
PubMed1994

Ability of oligonucleotides with certain palindromes to induce interferon production and augment natural killer cell activity is associated with their base length.

A synthetic 30-mer single-stranded oligodeoxyribonucleotide with a hexamer palindrome, AACGTT, induced IFN production and augmented NK activity in murine splenocytes. This effect does not appear to result from an antisense mechanism but rather is due to the palindrome. To clarify the required minimal size of the nucleotide, 10 kinds of 12- to 30-mer nucleotides were examined. Immunostimulatory activity of oligonucleotides 18 bases or more in length was observed and was proportional to the base length, with a maximum of 22-30 bases. On the other hand, the oligonucleotides 16 bases or less in length were not active even if they possessed the palindromic sequence. These results indicate that the immunostimulatory activity of oligonucleotides with certain palindromic sequences requires an oligonucleotide at least 18 bases long.

Interferon Inducers↗
PubMed1994

Binding of oligoguanylate to scavenger receptors is required for oligonucleotides to augment NK cell activity and induce IFN.

Specific palindromic sequences in synthetic oligonucleotides are required to induce IFN and augment IFN-mediated natural killer activity. To study the mechanism of IFN induction by oligonucleotides containing palindromic sequences, we investigated the possible target molecules of the oligonucleotides. Oligo-1, a 30mer single-stranded oligonucleotide with oligoG sequences next to the active palindromic sequence (AACGTT), had more activity than oligonucleotides with oligoA, oligoC, or oligoT sequences. The activity of oligo-1 was inhibited by a guanine homo-oligomer (G30), dextran sulfate, and polyvinyl sulfate. Oligo-1 bound to plastic-adherent mouse splenocytes, and the binding was inhibited by G30, dextran sulfate, and polyvinyl sulfate. Oligo-1 inhibited acetyl-LDL binding to the scavenger receptor on mouse splenocytes. These findings suggest that the binding of an extrapalindromic sequence to the scavenger receptor is required for the immunostimulatory activity of oligo-1.

Animals↗
PubMed1994

Lipofection of synthetic oligodeoxyribonucleotide having a palindromic sequence of AACGTT to murine splenocytes enhances interferon production and natural killer activity.

A synthetic 22-mer oligodeoxyribonucleotide having an AACGTT palindrome, AAC-22, induced interferon (IFN) production and augmented the natural killer (NK) activity in murine splenocytes, whereas its analogue, ACC-22, having an ACCGGT palindrome, did not. The binding of AAC-22 to splenocytes was not different from that of ACC-22. Lipofection of AAC-22 to splenocytes remarkably enhanced IFN production and NK cell activity, whereas that of ACC-22 caused little enhancement. These results strongly suggest that the prerequisite for IFN production is not the binding of AAC-22 to the cell surface receptors, but its penetration into the spleen cells.

Animals↗
PubMed1994

Synthetic oligonucleotides with certain palindromes stimulate interferon production of human peripheral blood lymphocytes in vitro.

We studied the ability of synthetic single-stranded 30-mer oligodeoxyribonucleotides (oligoDNAs) with three different kinds of hexamer palindromic sequence to induce interferon (IFN) production of human peripheral blood lymphocytes (PBL). When PBL was cultured with oligoDNA having a palindrome of AACGTT or GACGTC, IFN activity was detected by bioassay in the culture fluid after 8 h, and the amount of IFN reached the maximum after 18 h. IFN-alpha was predominantly produced, and small amounts of IFN-beta and IFN-gamma were also found. OligoDNA with the palindrome ACCGGT had no effect.

Base Sequence↗