Biomedical subjects

K Kariya

Publications and source records attributed to K Kariya.

At least 73 records · Page 4Linked to original sources

PubMed1994

Selective inhibition of dexamethasone-induced apoptosis in rat thymocytes by herbimycin A.

DNA fragmentation and cell death in rat thymocytes induced by dexamethasone were inhibited by herbimycin A but not by the other inhibitors of tyrosine kinase including genistein and tyrphostin. Herbimycin A also prevented the inter-nucleosomal DNA fragmentation induced by dexamethasone. On the contrary, apoptosis induced by DNA topoisomerase inhibitors such as camptothecin and etoposide were not affected by herbimycin A. These results demonstrate that dexamethasone-induced apoptosis is specifically inhibited by herbimycin A.

Animals↗

PubMed1994

An enhancer core element mediates stimulation of the rat beta-myosin heavy chain promoter by an alpha 1-adrenergic agonist and activated beta-protein kinase C in hypertrophy of cardiac myocytes.

In hypertrophy of cultured rat cardiac myocytes, alpha 1-adrenergic agonists activate protein kinase C (PKC) and up-regulate beta-myosin heavy chain (MHC). The 3300-base pair (bp) rat beta-MHC promoter is stimulated by both an alpha 1-agonist and a constitutively activated mutant of beta-PKC (Kariya, K., Karns, L. R., Simpson, P. C. (1991) J. Biol. Chem. 266, 10023-10026). Here, we report the convergence of alpha 1-adrenergic and beta-PKC signaling on the same element of the beta-MHC promoter. A 20-bp sequence in the beta-MHC promoter (-215/-196) was required for induction by both alpha 1-adrenergic stimulation and beta-PKC and conferred induction on a heterologous promoter. This sequence bound myocyte nuclear factor(s) through a 9-bp "enhancer core" (5'-TGTGGTATG-3'). A 3-bp mutation within the enhancer core which abolished factor binding also abolished inducibility of a 215-bp beta-MHC promoter. These results support the idea that beta-PKC is in the pathway for alpha 1-adrenergic regulation of beta-MHC transcription during cardiac myocyte hypertrophy. The enhancer core is the first PKC response element mapped by transfection of an activated PKC mutant, rather than by treatment with phorbol esters.

Animals↗

PubMed1994

Suppressive effects on cancer cell proliferation of the enhancement of superoxide dismutase (SOD) activity associated with the protein-bound polysaccharide of Coriolus versicolor QUEL.

The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses superoxide dismutase (SOD) mimicking activity. Examination was made of the suppressive effects of PS-K on cancer cell lines cultured in vitro. SOD activity of incorporated PS-K was 5.88 u/mg in LLC-WRC-256 (Walker 256 fibrosarcoma) cells and 4.73 u/mg in NRK-49F (rat normal kidney fibroblast) cells. SOD activity in both cell types was enhanced about 7-8 times that of the original PS-K. PS-K was not incorporated into H4-11-E or H4-11-E-C3 (rat hepatoma) cells. SOD activity of 1 mg/ml PS-K incubated with cell homogenates of LLC-WRC-256 cells for 6 hours increased from 0.68 u/mg to 1.35 u/mg. SOD activity of PS-K 1 mg/ml in 0.05 M phosphate buffer incubated with 50 microM NADPH increased from 0.68 u/mg. The consumption of NADPH at the same concentration was confirmed spectrophotometically by incubation with PS-K. The mechanism for the enhancement of SOD activity associated with PS-K is considered to be collaboration with NADPH as an electron donor in the cytoplasm of cancer cells whose SOD and coupling enzyme activities are significantly lower than in normal cells.

Animals↗

PubMed1994

Enhancement of anti-cancer activity of cisdiaminedichloroplatinum by the protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) in vitro.

The protein-bound polysaccharide of Coriolus versicolor QUEL (PS_K) expresses superoxide dismutase (SOD) mimicking activity. Examination was made of the effects of PS-K on cancer cell lines following administration of the anti-cancer drug cisdiaminedichloroplatinum (cisplatin). Cell proliferation of each cell line was inhibited markedly by cisplatin from 0.5 to 5 micrograms/0.5 ml per well. Fifty percent of the inhibitory concentration (IC50) was 0.33 micrograms/0.5 ml per well in NRK-49F and human ovarian cancer cells, and 1.5 micrograms/0.5 ml per well in H4-II-E. PS-K 50 micrograms/0.5 ml per well prevented cytotoxicity due to cisplatin toward NRK-49F, but enhanced the cytotoxicity on H4-II-E and human ovarian cancer cells. Increase in lipid peroxide and decrease in SOD activity were observed following an IC50 dose of cisplatin. With PS-K 50 micrograms/0.5 ml per well, all the above were augmented in H4-II-E and ovarian cancer cells, but diminished in NRK-49F cell line. PS-K may have effect on cancer patients through its combining with cisplatin.

Animals↗

PubMed1994

Oxidative stress relief for cancer-bearing hosts by the protein-bound polysaccharide of Coriolus versicolor QUEL with SOD mimicking activity.

The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses the mimetic activity of superoxide dismutase (SOD). Human cancer patients usually suffer from oxidative stress (OS). Examination was made to determine the capacity of this drug with SOD mimetic activity for relieving OS. Rats transplanted with Walker 256 fibrosarcoma showed OS on day 12. After confirming high levels of OS on day 13, PS-K50 mg/kg was intraperitoneally administered, and prompt decrease in O2-release from RBC was noted. The drug ceased to have any effect 24 hours following the first inoculation. Average OS in human cancer patients was found twice that in healthy persons. In human cancer patients perorally administered PS-K3.0 g/day, OS decreased to the normal level one day after the initial administration. Plasma lipid peroxide (LPO) in cancer patients treated with PS-K for 28 days increased and withdrawal of the drug led to decreased LPO.

Administration, Oral↗

PubMed1994

Suppression of cancer cell growth in vitro by the protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) with SOD mimicking activity.

The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses the mimicking activity of superoxide dismutase (SOD). Examination was made of the suppressive effects of PS-K on cancer cell lines cultured in vitro. The SOD activity of LLC-WRC-256 (Walker 256 fibrosarcoma) cell lines was less than that of NRK-49F (rat normal kidney fibroblast), H4-II-E (rat hepatoma) and H4-II-E-C3 (rat hepatoma) cell lines. This activity in Walker 256 fibrosarcoma cells increased by 3.6 times and H2O2 concentration, by 2.56 times by PS-K 500 micrograms/ml. Cell proliferation was consequently suppressed and living cells decreased to less than 50% of the cells cultured without PS-K. Catalase and glutathione peroxidase activity changed little by PS-K. The sensitivity of cancer cells to PS-K can be predetermined based on SOD activity in tumor tissue.

Animals↗

PubMed1994

Cloning of the rat alpha 1C-adrenergic receptor from cardiac myocytes. alpha 1C, alpha 1B, and alpha 1D mRNAs are present in cardiac myocytes but not in cardiac fibroblasts.

alpha 1-Adrenergic receptor (AR) activation in cardiac muscle has several different physiological effects that might be mediated through different alpha 1-AR subtypes. Two alpha 1-AR subtypes have been cloned from the rat, the alpha 1B and the alpha 1D; both are present in adult rat heart. A third subtype, the alpha 1C, cloned from the cow and human, was reported to be absent in the rat. However, we recently found alpha 1C mRNA in adult rat heart by using a partial alpha 1C cDNA. Thus, all three cloned alpha 1-AR subtypes are present in the heart, but it is unknown whether each is expressed in cardiac myocytes or in cardiac fibroblasts. In the present study, the full-length rat alpha 1C-AR was cloned from cultured neonatal cardiac myocytes. alpha 1C mRNA transcripts of 3, 9.5, and 11 kb were present in adult rat heart by Northern blot analysis. alpha 1B-, alpha 1C-, and alpha 1D-subtype mRNAs were each present in isolated adult and neonatal cardiac myocytes by RNase protection assay. In addition, cultured neonatal cardiac myocytes expressed the three alpha 1-AR subtype mRNAs. In contrast, none of the alpha 1-AR mRNAs was detected in cultured neonatal cardiac fibroblasts. In addition, alpha 1-ARs were absent in fibroblasts by [3H]prazosin binding and norepinephrine-stimulated [3H]inositol phosphate production. The absence of alpha 1-ARs in cardiac fibroblasts differs from beta-adrenergic and angiotensin II receptors, which are present in both cardiac fibroblasts and cardiac myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1994

Decrease in myeloperoxidase during differentiation of bone marrow cells by colony-stimulating factor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) induced the proliferation and differentiation of bone marrow cells of normal mice with a concomitant loss of myeloperoxidase activity. The decrease in the enzyme activity was due to a reduced level in the bone marrow cells. These findings indicate that myeloperoxidase is not merely a marker, but may also play a role in the differentiation of stem cells into granulocytes.

Animals↗

PubMed1993

Transcriptional enhancer factor-1 in cardiac myocytes interacts with an alpha 1-adrenergic- and beta-protein kinase C-inducible element in the rat beta-myosin heavy chain promoter.

In cultured rat cardiac myocytes, a 20-base pair sequence (-215/-196) of the rat beta-myosin heavy chain (MHC) promoter mediates induction by both alpha 1-adrenergic stimulation and a constitutively activated beta-protein kinase C (PKC), and binds cardiac myocyte nuclear factor(s) through an "enhancer core" element (5'-TGTGG-TATG-3') (Kariya, K., Karns, L. R., and Simpson, P. C. (1994) J. Biol. Chem. 269, in press). Here, we report identification of this enhancer core binding factor as the rat homologue of transcriptional enhancer factor-1 (TEF-1), a human transcription factor for viral enhancers. In gel mobility shift and immunoblot analyses, the myocyte factor and human TEF-1 were indistinguishable in terms of sequence recognition, mobility, and immunoreactivity. Furthermore, DNA binding activity for the beta-MHC enhancer core and TEF-1 immunoreactivity correlated closely. These results are the first to suggest a role for TEF-1 in transcriptional regulation by PKC. The data also provide direct evidence for interaction of TEF-1 with the beta-MHC promoter, supporting a function for TEF-1 in regulation of cellular gene expression, as well as viral, and outline a pathway for alpha 1-adrenergic regulation of beta-MHC gene transcription in cardiac myocytes.

Animals↗

PubMed1993

Median preoptic neurons projecting to the hypothalamic paraventricular nucleus are sensitive to blood pressure changes.

Twenty-one neurons in the median preoptic nucleus (MnPO) were antidromically activated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) in male rats under urethane anesthesia. The activity of these identified neurons was tested for a response to activation of peripheral baroreceptors, achieved by rising arterial blood pressure with an intravenous administration of the alpha-agonist metaraminol. Of the neurons tested, 14 displayed a reduction and 2 exhibited an increase in neuronal excitability that accompanied a 30- to 50-mmHg elevation in mean arterial pressure, while 5 were unresponsive. The results show that efferent pathways from the MnPO to the PVN may receive neural inputs from the peripheral baroreceptors, suggesting the involvement of the pathways in the control of cardiovascular function.

Action Potentials↗

PubMed1993

[Hemophilia A complicated with hepatocellular carcinoma].

A 60-year-old hemophiliac man complaining of abdominal discomfort was admitted on suspicion of hepatocellular carcinoma (HCC) by ultrasonography (US). When he was 22-year-old, blood transfusion was given for intra-abdominal hematoma due to an external wound and a diagnosis of moderate hemophilia A and non-A non-B type chronic hepatitis (later, C type chronic hepatitis) was made at the age of 40. After admission, HCC in the S6 segment of the liver was diagnosed by US, computerized tomography, magnetic resonance imaging and angiography. He was treated with transcatheter arterial embolization (TAE) and partial resection of the liver. Later, percutaneous ethanol injection therapy and TAE was performed because of the recurrence of HCC. He is now alive with no evidence of recurrence. The rate of infection with hepatitis C virus (HCV) is significantly high in hemophiliacs but, because of the replacement therapy, their life expectation has dramatically improved in last two decades. Therefore, it is speculated that the incidence of HCC in hemophiliacs will increase. We emphasize that regular US examination for HCV-positive hemophiliacs is important for the early detection of HCC.

Carcinoma, Hepatocellular↗

PubMed1992

Identification of a receptor binding site in the carboxyl terminus of human interleukin-6.

To identify a receptor binding site of human interleukin-6 (IL-6), we created a library of IL-6 variants with single amino acid substitutions in the last 15 residues (171-185) in the COOH terminus of IL-6. Twenty-seven IL-6 variants were tested for biological activity on a human hepatoma and a mouse hybridoma cell line. Most variants were additionally tested in a receptor binding assay using a human myeloma cell line. Several single amino acid substitutions in the COOH terminus of IL-6 were found to decrease biological activity significantly. This is especially seen in variants with amino acid substitutions that alter the postulated amphipathical alpha-helix structure between residues 178 and 183. The two highly conserved Arg residues at positions 180 and 183 seem to play a very important role in biological activity. The loss of biological activity in all inactive variants is completely paralleled by a decrease of IL-6 receptor binding, as determined by competition binding experiments. One mutant (Leu171) displayed a higher activity on human cells and a higher binding affinity to the receptor and can be considered an IL-6 agonist. It is concluded that the amphipathical alpha-helix structure in the COOH terminus of IL-6 is critical for ligand receptor interaction. Furthermore, the region between residues Ser178 and Arg183 (Ser-Leu-Arg-Ala-X-Arg) is identified as a receptor binding site in the COOH terminus of human IL-6.

Amino Acid Sequence↗

PubMed1992

Sympathetic modulation of the cardiac myocyte phenotype: studies with a cell-culture model of myocardial hypertrophy.

Myocardial hypertrophy is the common endpoint of many cardiovascular stimuli such as hypertension, myocardial infarction, valvular disease, and congestive failure. Catecholamines have long been implicated in the pathogenesis of myocardial hypertrophy, however, it is very difficult to sort out catecholamine mechanisms in vivo. We have developed a cell-culture model which excludes hemodynamic effects and allows the assignment of receptor specificity to catecholamine effects. Utilizing this system, we have shown that stimulation of the alpha 1 adrenergic receptor leads to the development of myocardial hypertrophy and results in the selective up-regulation of the fetal/neonatal mRNAs encoding skeletal alpha-actin and beta-MHC, a pattern similar to that seen with hypertrophy in-vivo. Utilizing a co-transfection assay, we have also obtained data that suggest that the beta-PKC isozyme is in a pathway regulating transcription of the beta-MHC isogene. Beta adrenergic stimulation of the cultured cardiac myocytes also results in a modest degree of hypertrophy, however, this effect may be dependent upon myocyte contractile activity and may involve, at least in part, the non-muscle cells present in the culture system.

Animals↗

PubMed1992

Increased monoamine turnover in the subfornical organ area following body fluid depletion.

To clarify whether monoaminergic inputs to the subfornical organ (SFO) area participate in fluid regulatory systems, we examined the effects of body fluid depletion on monoamine turnover in the region of the SFO using microdialysis techniques in rats. An iso-osmotic reduction of fluid volume following subcutaneous treatment with polyethylene glycol (PEG) significantly increased dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the SFO area. 5-hydroxytryptamine (5-HT) in the SFO area could be detected after the PEG treatment, while 5-HT was undetectable before the treatment. The data imply that both dopaminergic and serotonergic systems in the SFO area may be involved in controlling body fluid balance.

Animals↗

PubMed1992

[Effects of sodium hyaluronate on the nociceptive response of rats with experimentally induced arthritis].

Antinociceptive effects of sodium hyaluronate (Na-HA) were studied on the basis of improvement in the graded abnormal gait elicited by arthritis induced by intra-articular administration of monosodium urate crystal (MSU) to rats. One hour before MSU injection, intra-articular administration of a 1.0% solution of Na-HA with different molecular weights, ranging from 4.70 x 10(5) to 2.02 x 10(6) (HA-200), improved the score of abnormal gait in a molecular weight-dependent manner in the experimental arthritis model. Similarly, administrations of HA-200 at concentrations ranging from 0.1 to 1.0% prior to MSU treatment resulted in improvement of the score in abnormal gait in a dose-dependent manner. To elucidate the antinociceptive mechanisms of Na-HA, effects of pretreatment with Na-HA (1.0%) of different molecular weights on prostaglandin E2 (PGE2) and bradykinin (BK) releases in synovial fluid 3 hr after MSU injection were studied. Increases in PGE2 and BK concentration in the synovial fluid were depressed in a molecular weight-dependent manner by Na-HA (1.0%) pretreatment. These results indicate that Na-HA attenuates the nociceptive responses inflicted by the MSU-induced arthritis. Such an antinociceptive effect may be due to the inhibition of PGE2 and BK synthesis in the synovial joint of rats.

Analgesics↗

PubMed1992

Stereoselective conjugation of a uricosuric diuretic with glutathione by glutathione transferase 3-3.

1. The activity of glutathione (GSH) transferases in rat liver cytosol was inhibited by the (-) enantiomer of a uricosuric diuretic (6,7-dichloro-5[N,N-dimethylsulphamoyl]-2,3-dihydrobenzofuran-2-ca rboxylic acid, DBCA) in a concentration-dependent manner. Although the DBCA (+) enantiomer inhibited the activity of liver cytosol GSH transferases, it was less effective. 2. Among four purified GSH transferase isozymes obtained from rat liver cytosol, isozyme 3-3 showed stereoselective interactions with the enantiomers of DBCA. This isozyme most actively and preferentially catalysed the transfer of GSH to DBCA (-) enantiomer.

Animals↗

PubMed1992

[Bleeding time].

Bleeding time indicates the interaction of the platelets with the damaged vessel wall and the subsequent formation of the primary hemostatic plug. Bleeding time has been widely used in the diagnosis of bleeding disorders, especially thrombocytopenia, abnormalities in platelet function, vascular disorders, and von Willebrand's disease. There are a number of methods to perform the bleeding time test, but there are significant problems concerning sensitivity, specificity, and reproducibility. To study the inhibitory effects of monoclonal antibodies (anti-vWF, anti-GPIb, and anti-GPIIb/IIIa) on primary hemostasis, these antibodies were infused to normal pigs. Anti-vWF and anti-GPIb antibodies markedly prolonged the bleeding time and inhibited hemostatic plug formation. The anti-GPIIb/IIIa antibody completely inhibited ADP-and collagen-induced platelet aggregation, but no or only mild prolongation of bleeding time was observed. The quantitative bleeding time which measures both the time and the amount of blood loss is useful in the diagnosis of hemorrhagic disorders and in judging the efficacy of the treatment. It will provide important information to understand the mechanism of primary hemostasis.

Animals↗

PubMed1992

Mimicking of superoxide dismutase activity by protein-bound polysaccharide of Coriolus versicolor QUEL, and oxidative stress relief for cancer patients.

The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) has been found to express antioxidant activity as an "ion-radical scavenger" in diamine oxidation reactions. The mode of this expression was examined to determine whether the drug functioned as a simple radical scavenger or mimicked the action of superoxide dismutase (SOD). The latter was confirmed in both enzymatic and nonenzymatic superoxide anion radical (O2-.) producing systems in vitro. The SOD mimetic activity of PS-K was demonstrated by quantitative analysis of hydrogen peroxide as the end product of O2-., its formation being assisted catalytically by SOD or PS-K. Analysis by electron spin resonance also confirmed the SOD mimetic activity of PS-K in a xanthine-xanthine oxidase reaction. Relative SOD activity with PS-K was approximately 1/8,000 in a KO2-O2-.-producing system. The SOD mimetic activity of PS-K resisted treatment by 0.7N HCl, 0.7N NaOH, boiling for 30 minutes in a double water bath, and digestion by pronase. Fractionation according to differences in molecular mass caused no significant increase in relative SOD activity within a certain range of molecular mass, indicating that there is no definite molecule expressing SOD mimetic activity. Tumor-bearing rats and human patients with digestive tract cancer who suffered from oxidative stress were relieved by a single intraperitoneal administration of PS-K or a 1-day peroral prescription.

Animals↗