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Biomedical subjects

K Okamoto

Publications and source records attributed to K Okamoto.

At least 19 recordsLinked to original sources
PubMed1992

Enterotoxicity and immunological properties of two mutant forms of Escherichia coli STIp with lysine or arginine substituted for the asparagine residue at position 11.

Two variants of Escherichia coli heat-stable enterotoxin Ip, in which the amino acid residue at position 11 was substituted with lysine or arginine, were purified to near homogeneity from the culture supernatants of toxin-producing mutant strains. Neither the purified heat-stable enterotoxin Ip(Lys-11) nor the purified heat-stable enterotoxin Ip(Arg-11) showed a positive response in the suckling mouse assay or in the mouse intestinal loop assay. Furthermore, live bacteria producing these mutant heat-stable Ip enterotoxins did not cause fluid accumulation in mouse intestinal loops, in contrast to bacteria producing native heat-stable enterotoxin Ip. Nevertheless, antisera raised against both heat-stable enterotoxin Ip(Lys-11) and heat-stable enterotoxin Ip(Arg-11) neutralized the enterotoxic activity of native heat-stable enterotoxin Ip. These results demonstrate that heat-stable enterotoxin Ip(Lys-11) and heat-stable enterotoxin Ip(Arg-11) lose enterotoxicity but retain epitopes which are common to native heat-stable enterotoxin Ip.

Animals↗
PubMed1992

Inactivation of glibenclamide-sensitive K+ channels in Xenopus oocytes by various calmodulin antagonists.

In follicle-enclosed Xenopus oocytes, extracellular application of cromakalim (a K+ channel opener) or intracellular injection of cAMP induces the smooth outward K+ current which is inactivated by glibenclamide. We found that cromakalim- or cAMP-induced K+ currents in the oocytes were rapidly, reversibly and dose-dependently blocked by various drugs having a calmodulin antagonizing activity in common, namely, by a selective calmodulin antagonist (W-7), antipsychotics (trifluoperazine, chlorpromazine, haloperidol), an antidepressant (amitriptyline), a beta-adrenoceptor blocker (propranolol), a local anesthetic (lidocaine) and a calcium antagonist (prenylamine). W-7, trifluoperazine, chlorpromazine and prenylamine were relatively potent blockers. For example, IC50 values to block cromakalim (100 microM)-induced K+ currents were 12 microM for trifluoperazine and 16 microM for W-7, which were close to their IC50 values to inhibit Ca2+/calmodulin-dependent phosphodiesterase (an index of the potency of calmodulin antagonists). IC50 values to inhibit cAMP (20 pmol/oocyte)-induced K+ currents were 126 microM for prenylamine and 129 microM for chlorpromazine. The IC50 values of all drugs tested to block cromakalim or cAMP responses were significantly correlated with their calmodulin-antagonizing potencies. Isoproterenol-induced K+ currents in the oocytes were also dose-dependently inhibited by glibenclamide, W-7 and trifluoperazine. These results suggest the possibility that the activity of glibenclamide-sensitive K+ channels in follicle-enclosed oocytes are regulated by calmodulin or a calmodulin-dependent process.

Animals↗
PubMed1992

Action of Escherichia coli heat-stable enterotoxin II on isolated sections of mouse ileum.

When Escherichia coli STII was applied to the serosa of the ileum at a concentration of 40 micrograms/ml, an acceleration of the spontaneous motility and a weak contraction were induced 2-3 min later. The induction was not affected by the addition of atropine (10(-6) M), but was abolished by the addition of papaverine (10(-4) M). When STII was applied to the mucosa, the acceleration of the spontaneous motility appeared 7-8 min later, but a contraction was not induced. These results suggest that STII acts directly on muscle cell of the ileum and enhances the spontaneous motility of the intestine.

Animals↗
PubMed1992

Alpha-elastin coacervate as a protein liquid membrane: effect of pH on transmembrane potential responses.

A protein liquid membrane composed of coacervated alpha-elastin, a chemical fragmentation product of the biological elastic fiber protein, functioned as an amphoteric liquid ion-exchange membrane. Ionic permselectivities of the alpha-elastin coacervate membrane to a series of metal chlorides were investigated for the concentration-cell systems by the ordinary electrochemical measurements. Effects of pH on the transmembrane potential responses for NaCl, CaCl2, and MgCl2 systems were examined. Only in the Ca(2+)-containing system did potential responses stay at constant levels against the pH changes, whereas in the other systems, increasing pH caused potential changes, indicating an improvement of cationic permselectivity across the alpha-elastin coacervate membrane. It was suggested that the characteristic Ca2+ transport mechanisms across the alpha-elastin coacervate membrane are related in some way to the polypeptide backbone interactions specific and selective to Ca2+ ions.

Calcium↗
PubMed1992

Antihepatitis C virus status in hepatocellular carcinoma and the influence on clinicopathological findings and operative results.

Antihepatitis C virus (HCV) status was investigated in 100 patients undergoing hepatectomy for hepatocellular carcinoma (HCC) between 1980 and 1989. The clinicopathological findings and operative results, in patients with or without HCV marker, were compared retrospectively. The positivity rate of anti-HCV was 51 per cent. In this group there was a higher mean age, fewer symptoms, raised alanine aminotransferase level, higher 15-min indocyanine green clearance rate and earlier tumour stage compared with the anti-HCV negative group. Positive tumour margins and vascular invasion were seen less frequently in the anti-HCV positive group. HCC with HCV marker showed characteristic features of chronic non-A non-B hepatitis and of HCC originating from liver cirrhosis. There was a better cumulative 1-year survival rate for anti-HCV positive patients, but 3- and 5-year survival rates after hepatectomy were similar in both groups. Although HCV-related HCC had typical features of chronic non-A non-B hepatitis and a relatively early stage of tumour, biological features and operative results were similar with or without the HCV marker.

Adult↗
PubMed1992

Ubiquitin-positive intraneuronal inclusions in the extramotor cortices of presenile dementia patients with motor neuron disease.

Ubiquitin-positive intraneuronal inclusions were found in the extramotor cortices of ten presenile dementia patients with motor neuron disease. There were inclusions in the hippocampal granular cells and in the small neurons of the superficial layers of the temporal and frontal cortices. Bunina bodies were present in the anterior horn cells in all cases. These results suggest that ubiquitin-related cytoskeletal abnormalities are common in cerebral non-motor small neurons in these patients.

Adult↗
PubMed1992

Hepatic vascular and bile duct injury after ethanol injection therapy for hepatocellular carcinoma.

Three patients with serious hepatic vascular injury after percutaneous ethanol injection therapy for hepatocellular carcinoma (HCC) are described. In two cases, immediately after ethanol injection, liver function tests deteriorated and computed tomography (CT) showed a wedge-shaped low-density area due to liver infarction. In the other case, 1 year after ethanol injection, the intrahepatic bile duct in the right lobe was dilated and the right hepatic lobe atrophied. Endoscopic retrograde cholangiography showed stenosis of the main right hepatic duct. Since complications include both acute and delayed vascular injury after ethanol injection, patients should be followed for a long period after treatment.

Aged↗
PubMed1992

Cell-type-specific responsiveness to cAMP in cell differentiation of Dictyostelium discoideum.

In Dictyostelium discoideum, both prespore and prestalk differentiation require extracellular cAMP. We investigated the difference in inducibility of the two cell types by cAMP. Previous studies indicate that cAMP added in the early stage of development inhibits prespore differentiation, and this was confirmed using three species of prespore specific mRNAs. By contrast, early treatment with cAMP did not inhibit, but induced the expression of prestalk-specific mRNA. These results indicate that differentiation pathways of the two cell types have different processes in the early stage of development.

Animals↗
PubMed1992

Inhibition of human T-lymphocyte activation by macrolide antibiotic, roxithromycin.

Effects of macrolide antibiotic, roxithromycin (RXM) on human lymphocytes in culture were studied. The drug showed a dose-dependent inhibition of 3H-thymidine and 35S-methionine uptake responding to T cell mitogens and purified protein derivative of tuberculin (PPD). Activation by PPD, as assessed by 3H-thymidine uptake, was more sensitive to inhibition than the response to T cell mitogens. The drug produced a loss of blasts when added soon after transformation commenced. Immunosuppressive effects of RXM were further characterized by using four different types of metabolized RXM, RU 28111, RU 39001, RU 44981 and RU 45179. The most potent inhibitor of lymphocyte transformation was RU 45179, followed by RU 44981, RU 39001 and RU 28111 have little activity.

Cells, Cultured↗
PubMed1992

Influences of roxithromycin on cell-mediated immune responses.

We investigated the effects of roxithromycin (RXM), a synthesized macrolide antibiotic on murine cellular immune responses by examining the in vitro proliferative response of lymphocytes, interleukin 1 (IL-1) production and interleukin 2 (IL-2) production. RXM was orally administered to BALB/c mice at a dose of 5 mg/kg once a day for 42 days. Spontaneous blastic activity of lymphocytes prepared from mice administered with RXM for 7 days was higher than those from control mice. The activity peaked at the 14th day, and then decreased gradually to control levels by the 42nd day. Time kinetics of lymphocyte blastogenesis to concanavalin A showed a pattern similar to that observed in spontaneous blastic activity. Oral administration of RXM also influenced cytokine production; short-term (for 14 days) administration of RXM enhanced both IL-1 and IL-2 production but long-term (for 42 days) administration inhibited them.

Animals↗
PubMed1992

Sialyl cholesterol enhances the development of grafted neurons and motor recovery.

Trophic actions of alpha-sialyl cholesterol (SC) and its sialidase-tolerant derivative, alpha-(3 beta-hydroxysialyl) cholesterol (SCt), were carried out on the development of midbrain neurons both in vitro and in vivo transplantation studies. Low to moderate concentrations of SC (0.01 to 0.05 micrograms/ml) facilitated neurite extension but had no effects on cell survival of primary cultured midbrain neurons. However, high concentration of SC (0.1 micrograms/ml) disturbed both neurite genesis and cell survival. SCt had a similar effect on midbrain neurons. At higher concentrations, SC and SCt induced concentration-dependent morphological changes in astrocytes from flat to fibrous. The effect on astrocytes was stronger in SCt than SC. At highest concentration tested (20 micrograms/ml), the proliferation of astrocytes was completely blocked, cells became detached and finally died. This effect of SC and SCt was partially blocked by simultaneous application of aFGF. Following dopaminergic cell grafting in vivo, SC and SCt had biphasic effects: a low dose (0.2 mg/kg, SC) enhanced motor recovery at 4 and 6 weeks after transplantation, while the highest dose (20 mg/kg, SC) disturbed motor recovery at all periods tested. These effects on motor recovery were paralleled by an effect on neurite genesis as studied by tyrosine hydroxylase immunostaining. Thus, at low concentrations, SC and SCt are neurotrophic agents that stimulate the development and differentiation of dopaminergic neurons.

Animals↗
PubMed1992

Macrophages in protective immunity to Hymenolepis nana in mice.

When mice were treated with carrageenan just before infection with eggs of Hymenolepis nana, they failed to exhibit sterile immunity to the egg challenge, with evidence of a decrease in the number of peripheral macrophages (Mø) and the rate of carbon clearance. Although there were high levels of interleukin-1 (IL-1) released into the intestinal tracts of the parasitized mice at challenge infection, there was almost no release of IL-1 in those treated with carrageenan just before challenge. These results strongly suggest that Mø have an important role in protective immunity to H. nana in mice.

Animals↗
PubMed1992

Therapeutic effect of ansamitocin targeted to tumor by a bispecific monoclonal antibody.

We have constructed a murine hybrid hybridoma that secretes a bispecific monoclonal antibody (mAb) by fusing a hybridoma secreting an anti-ansamitocins mAb with a hybridoma secreting an anti-human transferrin receptor (TfR) mAb that binds to human A431 epidermoid carcinoma cells. The bispecific mAb, reactive to both ansamitocins and TfR, was purified by a combination of hydrophobic column chromatography and hydroxyapatite high-performance liquid chromatography, and evaluated in in vivo experiments using human tumor cell-implanted nude mice. Ansamitocin P-3 targeted through one of the antigen combining sites of the bispecific mAb was potentially more effective in suppressing the growth of established A431 tumor xenografts implanted on nude mice than unconjugated ansamitocin P-3 or the immunoconjugate of ansamitocin P-3 and monospecific anti-ansamitocins antibody, and the targeted ansamitocin P-3 finally eradicated the tumor mass. The bispecific mAb also played an important role in reducing such undesirable side-effects of ansamitocin P-3 as the loss of body weight, the damage to liver functions and the decrease in the number of white blood cells.

Animals↗
PubMed1992

Fundamental morphological changes in human olivary hypertrophy.

Morphological features of neurons in human inferior olivary nuclei were studied in 6 autopsied patients with dentato-olivary pathway lesions, who had survived for between 6 days and 15 months. Central chromatolysis-like neuronal enlargements were already present in the acute cases. Electron microscopy revealed round, homogeneous and electron-dense granules, varying in diameter from 0.15 micron to 2.5 microns, occurring frequently within the rough endoplasmic reticulum (ER) in the chromatolytic neurons of all 6 patients. No similar granules were observed in 6 controls. The vacuoles were due to dilatation of the rough ER, and often contained floccular materials. Neurofilamentous hyperplasia in the neurons was more frequently seen in the chronic cases. These findings suggest that the fundamental changes in the neurons in olivary hypertrophy occur within the rough ER.

Aged↗
PubMed1992

Blockade by antiarrhythmic drugs of glibenclamide-sensitive K+ channels in Xenopus oocytes.

1. The outward K+ current induced by KRN2391 (K+ channel opener) in Xenopus oocytes is blocked by glibenclamide. We have investigated the effects of various classes (I-IV) of antiarrhythmic drugs on this KRN2391-induced response. 2. All class I antiarrhythmic drugs (Na+ channel blockers) tested concentration-dependently suppressed KRN2391-induced responses with the rank order of potency (IC50 in microM), disopyramide (17.8) > aprindine (29.5) > propafenone (63.1) > ajmaline (145) > quinidine (151). Flecainide, SUN1165, lignocaine, mexiletine and procainamide were much less potent (IC50, 450- > 1000 microM) than quinidine. 3. The class II antiarrhythmic drugs (beta-blockers), timolol, (-)- and (+/-)- propranolol, and (+)- propranolol (a non-beta-blocker) inhibited KRN2391-induced K+ currents in a concentration-dependent manner with values for IC50 (microM) of 79, 131, 151 and 129, respectively, whilst butoxamine, oxprenolol, alprenolol, pindolol, nadolol, metoprolol and acebutolol were either weak (IC50, 300 microM-600 microM) or virtually inactive (IC50, > 1000 microM). 4. The class III antiarrhythmic drugs, amiodarone and (+)-sotalol scarcely affected KRN2391 responses. 5. All class IV drugs (Ca2+ antagonists) tested suppressed KRN2391-induced responses in a concentration-dependent manner with an IC50 of 6.3 microM for bepridil, 38 microM for prenylamine, 85 microM for verapamil and 135 microM for diltiazem. 6. In conclusion, antiarrhythmic drugs of classes I, II and IV potently blocked glibenclamide-sensitive K+ channels in Xenopus oocytes.

Adrenergic beta-Antagonists↗