Biomedical subjects

K Koike

Publications and source records attributed to K Koike.

At least 559 records · Page 31Linked to original sources

PubMed1990

Synergistic action of phorbol ester and IL-3 in the induction of "connective tissue-type" mast cell proliferation.

12-O-Tetradecanoylphorbol-13-acetate (TPA), a tumor-promoting phorbol ester, induced the proliferation of connective tissue-type mast cells (CTMC) synergistically with IL-3 in a methylcellulose culture, as well as with IL-4. The culture of single CTMC and the serum-free culture of CTMC fractionated by Percoll density gradient centrifugation showed that this synergistic action of IL-3 and TPA required no effects of accessory cells or other humoral factors. Although the populations of CTMC acted on by TPA and IL-4 seemed to be close to each other, the velocity of colony growth induced by the simultaneous stimulation of the combination of TPA and IL-4 was faster than that induced by either TPA or IL-4 in the presence of IL-3. In addition, the addition of anti-IL-4 antibody did not neutralize the effect of TPA on the proliferation of CTMC. These results suggest that TPA and IL-4 act on the proliferation of CTMC synergistically with IL-3 via a different pathway. Beside TPA, other phorbol derivatives capable of activating protein kinase C (PKC) induced the proliferation of CTMC synergistically with IL-3, but phorbol derivatives which were unable to activate PKC did not. These results indicate that the activation of PKC is involved in the process of TPA action on the proliferation of CTMC. Furthermore, the facts that 1-oleoyl-2-acetylglycerol, which activated membrane PKC transiently, and staurosporine, which has been reported to inhibit PKC, did not induce the proliferation of CTMC in the presence of IL-3 and that the effect of TPA was exhibited by the sustained stimulation suggest that the action of TPA on the proliferation of CTMC requires at least two steps. The first one is the primary activation of membrane PKC and the second one is the disappearance of PKC from the cells, "down-regulation."

Alkaloids↗

PubMed1990

Integrated structures of HBV DNA in chronic hepatitis and hepatoma tissues.

Cellular DNAs of chronically hepatitis B virus (HBV)-infected human livers were analysed by Southern blot hybridization for the presence of integrated HBV DNA. In 15 out of 16 tissue samples, random HBV DNA integration was evident. By molecular cloning and structural analyses of 19 integrants from 3 chronic hepatitis tissues, rearrangement of HBV DNA with inverted duplication or translocation of cellular flanking DNA at the virus-cell junction was noted. Thus, the rearrangement of HBV DNA or cellular flanking DNA not to be a specific incident of HCC formation. Analyses of various integrants bearing HBV DNA rearrangement and their cellular counterpart DNAs failed to indicate any gross structural alteration in cellular DNA except for a small deletion at the integration sites, indicating HBV DNA rearrangement with inverted duplication to possibly occur prior to integration. Based on nucleotide sequencing analyses of virus-virus junctions, a mechanism of this inverted duplication of HBV DNA is proposed, in which an illegitimate recombination may take place by means of a patchy homology on one side of adjoining viral sequences.

Base Sequence↗

PubMed1990

Genuine CD7 expression in acute leukemia and lymphoblastic lymphoma.

CD7 has been used as a valuable marker for normal and malignant T cells and also for a proportion of acute nonlymphocytic leukemia (ANLL) cells. Difference in reactivity was noticed among CD7 antibodies, however, when tested against ANLL cells and myeloid/monocytoid cell lines; Tp40 antibody produced in our laboratories was not reactive with the HL-60 promyelocytic line, whereas 4A antibody was reactive, even though both detected a quite similar or an identical epitope on CD7 molecule. Preincubation of HL-60 cells with human immunoglobulin preparation clearly negated the reactivity by 4A, suggesting that 4A antibody is not reactive to CD7 itself, but it probably binds with immunoglobulin G Fc receptors expressed on HL-60 cells. Five cases of ANLL which were positive with 4A antibody were selected and tested with Tp40 antibody, and only two were found to be positive. Expression of CD7 mRNA in these two cases (but not in other cases) was also demonstrated by Northern blotting with a cDNA probe for CD7 recently cloned in our laboratories, indicating that CD7 is expressed on a certain fraction of ANLL, although the positive cases may be smaller than the reports so far appeared. A Northern blot study was also conducted with two acute lymphocytic leukemia cases and one lymphoblastic lymphoma case with CD7+, CD2-/+/-, CD5-/+/- phenotype and germline T cell receptor beta genes. CD7 mRNA is expressed in all three cases and CD3 mRNA is also observed in two cases, suggesting that these tumor cells are of T precursor origin.

Acute Disease↗

PubMed1990

Interaction of newly synthesized N-cyclopropylmethyl derivatives of (-)-6 beta-acetylthionormorphine with opioid receptors.

1. Analgesic activities of N-cyclopropylmethyl derivatives of (-)-6 beta-acetylthionormorphine, KT-89 and KT-90 and their interactions with opioid receptors were studied. 2. KT-89 and KT-90, as well as morphine inhibited the twitch response of the guinea-pig ileal preparation to electrical stimulation. Their pD2 values indicated that KT-89 and KT-90 are about 6.5 and 10 times as potent as morphine, respectively. In guinea-pig ileal preparation KT-89 and KT-90 also behaved as a mu-antagonist. 3. In rabbit vas deferens which contains kappa-receptors, these substances inhibited the twitch response to electrical stimulation and were about 6 times as potent as dynorphin. 4. Their effects on specific binding of [3H]naloxone (mu-selective ligand), [3H]ethylketocyclazocine (kappa-selective ligand) and [3H]D-Ala2-D-Leu5-enkephalin (delta-selective ligand) to the synaptosomal fractions from rat brain were tested. Though both drugs had a nonselectively high affinity to mu-, kappa- and delta-receptors, affinities of KT-89 and KT-90 to kappa-receptors were about 6 and 13 times higher than that of morphine, respectively. 5. Analgesic activities of KT-89 and KT-90 were 6 and 10 times as potent as morphine in an acetic acid-induced writhing test, and 4 and 5 times as potent in a pressure test. 6. The present results suggest that KT-89 and KT-90 induced analgesic actions are mediated through an activation of kappa-receptors. Both the drugs acted as delta-receptor antagonists. Further experiments are needed to study effects of their property as a delta-antagonist on analgesic action.

Analgesics↗

PubMed1990

Thermodynamic analysis of beta-adrenergic partial agonists (befunolol and carteolol) interaction with low and high affinity binding sites of beta-adrenoceptors in guinea-pig taenia caecum.

1. Effects of temperatures (0, 10 and 32 degrees C) on the bindings of beta-adrenergic partial agonists, befunolol and carteolol, with beta-adrenoceptors were studied using the microsomal fractions from the guinea-pig taenia caecum. 2. The affinities of befunolol and carteolol to the low affinity binding site were higher at low temperatures, whereas those to the high affinity binding site were not influenced by change in temperature. 3. The interactions of the low affinity binding site with befunolol and carteolol decreased both enthalpy and entropy. The interactions of both the drugs with the high affinity binding site increased only entropy. 4. These results support our view that beta-adrenoceptors contain two different affinity binding sites and that the interactions of beta-adrenergic partial agonists with the low affinity binding site induce the beta-adrenomimetic action, whereas the competitive antagonism by the beta-partial agonists and beta-adrenoceptor blockers is due to their ability to compete with beta-stimulant for the high affinity binding site.

Adrenergic beta-Agonists↗

PubMed1990

Stereoselectivity in beta-adrenomimetic and beta-adrenolytic actions of carteolol, a beta-adrenoceptor blocker with intrinsic sympathomimetic action in guinea-pig taenia caecum.

1. The beta-adrenomimetic and beta-adrenolytic activities of S(-) and R(+) isomers of carteolol, a beta-adrenergic partial agonist (a beta-adrenoceptor blocker with intrinsic sympathomimetic action) were tested in the guinea-pig taenia caecum. 2. The beta-adrenoceptor blocking activities (pA2 values) of S(-) and R(+) isomers of carteolol were significantly larger than the corresponding beta-adrenomimetic activities (pD2 values), supporting our views that beta-adrenoceptors contain two different binding sites; high and low affinity sites. 3. In beta-adrenoceptor blocking action S(-) carteolol was about 10 times as potent as R(+) carteolol while beta-adrenomimetic action of S(-) carteolol was about 2 times as potent as that of R(+) carteolol. Further, intrinsic activity for S(-) carteolol was slightly but significantly larger than that for R(+) carteolol. 4. These results suggest that the binding site for competitive antagonism between S(-) isoprenaline and S(-), R(+) and RS(+/-) carteolol is more stereoselective than the binding site to induce beta-adrenomimetic action.

Adrenergic beta-Agonists↗

PubMed1990

Pharmacological properties of newly synthesized derivatives of (-)-6 beta-acetylthionormorphine and their interactions with opioid receptors.

1. Some pharmacological properties of newly synthesized derivatives of (-)-6 beta-acetylthionormorphine, AcS-morphine (KT-88), KT-89 and KT-90 and their interactions with opioid receptors were studied. 2. AcS-morphine was about twice as potent as morphine in the inhibitory action of the twitch response of the guinea-pig ileal preparation to electrical stimulation and about 5 times as potent as morphine in the analgesic action in the rats. Both the effects of AcS-morphine were inhibited by naloxone, suggesting that the site of action of AcS-morphine is mu-receptors. 3. Analgesic activities of KT-89 and KT-90 were about 6 and 10 times as potent as morphine in an acetic acid-induced writhing test and about 4 and 5 times as potent as in a pressure test. 4. As the analgesic action of KT-90 was antagonized by norbinaltorphimine, the site of action of KT-90 is concluded to be kappa-receptors. Furthermore, KT-89 and KT-90 behaved as antagonists on mu-receptors. 5. The present results suggest that AcS-morphine which is N-methyl derivative, as well as morphine, has a selectively high affinity to mu-receptors, and that KT-89 and KT-90 which are N-cyclopropylmethyl derivatives have nonselectively high affinities to mu-, kappa- and delta-receptors.

Animals↗

PubMed1990

Molecular cloning and characterization of human pyruvate dehydrogenase beta subunit gene.

A genomic clone encompassing the entire gene for the human pyruvate dehydrogenase beta subunit (PDH beta) has been isolated by screening a leukocyte genomic library with a nick-translated human foreskin fibroblast PDH beta cDNA probe. The 18-kilobase clone was characterized by restriction enzyme analysis, extensive DNA sequencing, and primer-extension analysis. The PDH beta structural gene is composed of 10 exons and 9 introns. All intron-exon splice junctions follow the GT/AG rule. The Alu family was found in introns 2 and 8. The 5' flanking region of the PDH beta gene contains a "CAAT" consensus promoter sequence but no "TATA" sequence. Primer-extension analysis indicated that the PDH beta gene transcription start site is an adenine residue located 132 bases upstream from the initiation codon in exon 1.

Amino Acid Sequence↗

PubMed1990

Trans-activation function of a 3' truncated X gene-cell fusion product from integrated hepatitis B virus DNA in chronic hepatitis tissues.

To investigate the expression and transactivation function of the X gene in integrated hepatitis B virus (HBV) DNA from chronic hepatitis tissues, a series of transfectants containing cloned integrated HBV DNAs was made and analyzed for X mRNA expression and trans-activation activity by using a chloramphenicol acetyltransferase assay. Most of the integrated HBV DNAs expressed X mRNA and encoded a product with trans-activation activity in spite of the loss of the 3' end region of the X gene due to integration. From cDNA cloning and sequence analysis of X mRNA transcribed from native or integrated HBV DNA, the X protein was found to be translated from the X open reading frame without splicing. For integrated HBV DNA, transcription was extended to a cellular flanking DNA and an X gene-cell fusion transcript was terminated by using a cellular poly(A) signal. The amino acid sequence deduced from an X-cell fusion transcript indicated truncation of the carboxyl-terminal five amino acids, but the upstream region of seven amino acids conserved among hepadnaviruses was retained in the integrated HBV DNA, suggesting that this conserved region is essential for the transactivation function of the X protein. These findings support the following explanation for hepatocarcinogenesis by HBV DNA integration: the expression of a cellular oncogene(s) is transactivated at the time of chronic infection by the increasing amounts of the integrated HBV gene product(s), such as the X-cell fusion product.

Amino Acid Sequence↗

PubMed1990

X protein of hepatitis B virus resembles a serine protease inhibitor.

The X protein of hepatitis B virus (HBV) has been shown to be a trans-activator for viral and cellular genes. Amino acid sequences in X protein were found to be highly homologous to functionally essential sequences in the "Kunitz domain," characteristic of Kunitz-type serine protease inhibitors. Mutations at these sequences completely abolished trans-activation. Consequently, HBV X protein resembles a serine protease inhibitor or its analogue, and may bring about trans-activation by activating certain transcriptional factors through proteolytic cleavage alteration.

Amino Acid Sequence↗

PubMed1990

Structural rearrangement of integrated hepatitis B virus DNA as well as cellular flanking DNA is present in chronically infected hepatic tissues.

Cellular DNAs from human livers chronically infected with hepatitis B virus (HBV) were analyzed by Southern blot hybridization for the presence of integrated HBV DNA. In 15 of 16 chronically infected hepatic tissues, random HBV DNA integration was evident. By molecular cloning and structural analyses of 19 integrants from three chronically infected hepatic tissues, deletion of cellular flanking DNA in all cases and rearrangement of HBV DNA with inverted duplication or translocation of cellular flanking DNA at the virus-cell junction in some cases were noted. Thus, the rearrangement of HBV DNA or cellular flanking DNA is not a specific incident of hepatocellular carcinoma formation. Detailed analyses of various integrants bearing rearranged viral DNA failed to indicate any gross structural alteration in cellular DNA, except for a small deletion at the integration site, indicating that viral DNA rearrangement with inverted duplication possibly occurs before integration of HBV DNA. Based on nucleotide sequencing analyses of virus-virus junctions, a one- to three-nucleotide identity was found. A mechanism for this inverted duplication of HBV DNA is proposed in which illegitimate recombination between two complementary viral strands may take place by means of a nucleotide identity at the junction site in a weakly homologous region (patchy homology) on one side of adjoining viral sequences. For virus-cell junctions, the mechanism may be basically similar to that for virus-virus junctions.

Adolescent↗

PubMed1990

Activation of retrovirus in transgenic mice: association with development of olfactory neuroblastoma.

A line of transgenic mice that express the human adenovirus type 12 E1A and E1B genes under the regulatory control of the mouse mammary tumor virus long terminal repeat was studied. Mice from this line develop olfactory neuroblastomas at approximately 6 months of age. Large numbers of type C retrovirus (ecotropic murine leukemia virus) particles were found in the tumor rosettes. No similar examples of virus activation were identified in tumors from other transgenic experiments. Examination of spontaneous olfactory neuroblastomas from three domestic cats also demonstrated retrovirus in tumor rosettes.

Adenovirus Early Proteins↗

PubMed1990

Relationship between sensitivity and density of muscarinic receptors in single smooth muscle cells of guinea pig taenia caecum prepared under three conditions.

The relationship between the sensitivity (the pD2 value) of carbachol and the density (the total concentration of receptors) of muscarinic receptors using single cells from the guinea pig taenia caecum prepared with a mixture of crude collagenase and trypsin inhibitor, purified collagenase alone, and a mixture of purified collagenase and papain was examined. The sensitivity of the single cells prepared with a mixture of purified collagenase and papain was about 10 times more effective than that of the single cells prepared under other conditions. The dissociation constant of [3H]quinuclidinyl benzilate (QNB) and Hill's coefficient did not change in the single cells prepared under the three conditions, though the maximum binding sites were significantly greater in the cells prepared with the mixture of purified collagenase and papain than in those prepared by other means. These results suggest that the increase in the sensitivity of carbachol obtained in the single cells prepared with this mixture is due to the increase in the density of muscarinic receptors and also suggest that the effects of this enzyme mixture may be due to an increase in the incorporation of newly synthesized receptors and (or) changes in receptor turnover.

Animals↗

PubMed1990

Caudal mediastinal node lymph flow in sheep after histamine or endotoxin infusions.

To determine whether intrathoracic nonpulmonary structures (caudal mediastinal node or esophagus) are reputed to affect lung lymph dynamics, we studied anesthetized, open-thorax, prone, ventilated sheep in which all lung afferent lymphatics to the caudal mediastinal node were eliminated. When we increased left atrial pressure by 20 cmH2O in four sheep, there was no effect on caudal mediastinal node efferent lymph flow or protein concentration, thus providing the completeness of the surgical preparation. In four sheep, intravenous histamine infusions (3 micrograms base.kg-1.min-1) had no effect on caudal mediastinal node lymph flow or protein concentration. In seven sheep with intact lung lymphatics, Escherichia coli endotoxin infusion (1 microgram/kg over 20 min) increased lymph flow with high lymph protein concentration during the late phase (2-6 h). In seven sheep, after all lung lymphatic afferents had been cut, endotoxin did not affect caudal mediastinal node lymph flow, although lymph protein concentration was decreased in the early 0-2 h, "hypertensive") phase. We conclude that at the concentrations tested, which are those regularly used in sheep lung experiments, the effects of histamine and endotoxin on caudal mediastinal node lymph flow and protein concentration are limited to the lung.

Animals↗

PubMed1990

Dopamine inhibits the arachidonate and prolactin release stimulated by thyrotropin-releasing hormone through an islet-activating protein-sensitive GTP-binding protein in anterior pituitary cells.

Coupling of the dopamine (DA) receptor to the pathway of arachidonate (AA) through the islet-activating protein (IAP)-sensitive GTP-binding (G) protein was examined in primary cultures of anterior pituitary cells. The inhibitions by 1 microM DA of the stimulations of prolactin (PRL) release by 100 nM thyrotropin-releasing hormone and by 10 microM calcium ionophore A23187 were blocked by 100 ng/ml IAP. DA at 1 microM did not inhibit the release of [3H]-AA induced by 100 mU/ml phospholipase A2 (PLA2), but it inhibited the release of PRL induced by 100 mU/ml PLA2. This inhibition was blocked by 100 ng/ml IAP. IAP also blocked the inhibitions by DA of the releases of PRL by 5 microM AA and by 5 microM 5-hydroxyeicosatetraenoic acid. These results suggest that the DA receptor on lactotrophs is coupled to the pathway following the release of AA (lipoxygenase) through the IAP-sensitive G protein.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1990

Adenosine 3',5'-cyclic monophosphate enhances dopamine accumulation in rat hypothalamic cell culture containing dopaminergic neurons.

The regulation of dopamine accumulation in cultured rat hypothalamic cells by adenosine 3',5'-cyclic monophosphate (cAMP) was investigated in cultures of newborn rat hypothalamic cells. Both dibutyryl cAMP, (Bu)2-cAMP, and forskolin enhanced [3H]dopamine accumulation in a dose-dependent manner. cAMP also enhanced [3H]dopamine accumulation, but to a lesser degree. Neither n-butyrate nor adenosine alone enhanced [3H]dopamine accumulation. (Bu)2-cAMP had no effect on basal efflux of [3H]radioactivity. The effect of (Bu)2-cAMP appeared on day 5 of culture, reached a maximum on day 6, and then rapidly decreased. These results suggest that dopamine uptake by cultured rat hypothalamic cells is regulated by intracellular cAMP.

Adenosine↗

PubMed1990

Induction by tumor necrosis factor-alpha of rapid release of immunoreactive and bioactive luteinizing hormone from rat pituitary cells in vitro.

Tumor necrosis factor-alpha (TNF-alpha) is secreted by activated monocytes and other immune cells. This paper reports studies on the effects of TNF-alpha on the releases of pituitary hormones such as luteinizing hormone (LH), follicle-stimulating hormone, prolactin (PRL) and adrenocorticotropic hormone (ACTH). The addition of recombinant human TNF-alpha (rTNF-alpha) to cultures of pituitary cells resulted in significantly increased releases of gonadotropins, PRL, and ACTH for up to 30 min, but not later. rTNF-alpha, like GnRH, also stimulated the release of bioactive LH. In addition, rTNF-alpha induced production of an interleukin-6 (IL-6)-like molecule by pituitary cells. As IL-6 induces the releases of multiple hormones from pituitary cells, our data suggest that rTNF-alpha may stimulate the releases of multiple pituitary hormones through IL-6 production as well as by its direct action on pituitary cells.

Adrenocorticotropic Hormone↗

PubMed1990

Effect of aging on the response of guinea pig trachea to isoprenaline.

To study the effect of aging on the beta-adrenergic receptor potency of isoprenaline, tracheas from 3-, 6-, 10-, 40- and 100-week-old guinea pigs were used as test tissues. The pD2 values (potency) of isoprenaline increased with age in tracheas treated with corticosterone, but decreased in untreated tracheas. The pA2 value of propranolol against isoprenaline estimated in the treated tracheas did not change with age. Specific binding of [3H]-dihydroalprenolol to the microsomal fractions from the tracheal muscles from 6-, 10- and 40-week-old guinea pigs was analyzed with Scatchard plots. The capacity of maximum binding sites of [3H]-dihydroalprenolol increased with increasing age, while its dissociation constant did not change. Age-related increase in the potency of isoprenaline in the tracheas treated with corticosterone is considered to be due to the increase in the total amount (density) of beta-adrenoceptors. However, the potency of the drug in untreated tracheas decreased with age. These results suggest that extraneuronal uptake plays an important role in the beta-adrenergic action of isoprenaline in older (40 and 100 weeks) guinea pigs.

Aging↗