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Biomedical subjects

Y Okamoto

Publications and source records attributed to Y Okamoto.

At least 19 recordsLinked to original sources
PubMed1992

A novel orally active inhibitor of IL-1 generation: synthesis and structure-activity relationships of 3-(4-hydroxy-1-naphthalenyl)-2-propenoic acid derivatives.

A new series of 3-(4-hydroxy-1-naphthalenyl)-2-propenoic acids was prepared and the inhibitory activities of its members on IL-1 generation were evaluated both by in vitro systems using human monocytes and/or rat exudated macrophages stimulated with LPS, and by an in vivo system using the rat CMC-LPS air-pouch model. Many compounds in this series were found to be potent inhibitors of IL-1 generation both in vitro and in vivo. Structure-activity relationships indicated that in the rat CMC-LPS air-pouch model by oral administration the (Z)-2-substituted propenoic acids with 3-alkoxy, 5-alkyl, and 4-hydroxy substituents on the naphthalene ring exhibit optimal inhibition. Among the compounds evaluated, (Z)-3-(5-ethyl-4-hydroxy-3-methoxy-1-naphthalenyl)-2-methyl-2-propeno ic acid (20a), which inhibited IL-1 generation from human monocytes with an IC50 value of 3.0 microM and had an IC50 value of 1.4 microM for rat exudated macrophages, showed the most potent inhibitory activity in the rat CMC-LPS model by oral administration. Compound 20a also showed antiinflammatory effects in animal models of inflammation.

Acrylates↗
PubMed1992

D-galactosamine-induced cell damage enhances specific binding of prostaglandin E1 to rat hepatocytes.

Specific bindings of [3H]prostaglandin E1 ([3H]PGE1), 125I-glucagon and [3H]norepinephrine to D-galactosamine (GalN)-treated rat hepatocytes in primary culture were investigated. After a two hour-treatment with GalN (1 and 10mg/ml), hepatocytes showed an enhanced specific binding to [3H]PGE1, whereas 125I-glucagon binding was little affected and [3H]norepinephrine binding was strongly diminished. Scatchard plot analysis indicated an increase of binding sites of [3H]PGE1. This unusual manner of [3H]PGE1 binding is suggested to indicate a special property of PGE1 receptor and may be associated with the cytoprotective effect of prostaglandins.

Alprostadil↗
PubMed1992

Identification of epitopes associated with different biological activities on the glycoprotein of vesicular stomatitis virus by use of monoclonal antibodies.

Thirteen monoclonal antibodies (MAbs) to the glycoprotein (G) of vesicular stomatitis virus (VSV) serotype Indiana were prepared and examined for their effects on various biological activities of VSV, including in vitro infection, hemagglutination, adsorption to cells, and mediation of cell fusion. Competitive binding assays with these MAbs revealed the presence of at least seven distinct antigenic determinants (epitopes) on the G protein. In some cases, overlappings among epitopes to various degrees were observed as partial inhibition or binding enhancement. The MAbs to all the epitopes but one (epitopes 1-6) reacted with the denatured G protein in a Western immunoblot analysis. Four of the epitopes (epitopes 2, 4, 5, and 7) were involved in neutralization and two (epitopes 1 and 2) in hemagglutination inhibition. None of the MAbs inhibited the adsorption of radiolabeled VSV to BHK-21 cells; the MAbs to epitope 2 slightly enhanced the virus adsorption. All neutralization epitopes except epitope 2 (epitopes 4, 5, and 7) were associated with inhibition of VSV-mediated cell fusion. These results show a direct spatial relationship between the epitopes recognized by the MAbs and functional sites on G protein and further insights into the structure and function of G protein.

Adsorption↗
PubMed1992

Combination of recombinant cytokines fails to produce ex vivo expansion of human blood hematopoietic progenitor cells.

The concept of ex vivo expansion of the human progenitor cell population was tested in this study. In the presence of interleukin-3 and -6 we compared the abilities of various liquid culture conditions of human blood-derived hematopoietic progenitor cells to yield a suitable condition for the expansion of blood progenitor cells. Although the best result was obtained in the gastpermeable bag culture system, the enhancement effect (maximum of 3.8-fold for granulocyte/macrophage colony-forming units and 3.0-fold for erythroid burst-forming units) lasted for only a short period (less than 6 d). The results of this study are disappointing for clinical use, and attempts with currently available technology appear to be limited in their potential.

Adolescent↗
PubMed1992

Glucagon, insulin and somatostatin secretion in response to sympathetic neural activation in streptozotocin-induced diabetic rats. A study with the isolated perfused rat pancreas in vitro.

Changes in glucagon, insulin and somatostatin secretion induced by electrical splanchnic nerve stimulation were examined in rats treated with streptozotocin as neonates and as adults. In order to study the direct neural effects we used the isolated perfused rat pancreas with intact left splanchnic nerve in vitro. In normal rats splanchnic nerve stimulation causes significant decreases in insulin (30-40%) and somatostatin (30-50%) secretion at both 16.7 mmol/l and 1 mmol/l glucose concentrations. In the neonatal streptozotocin-diabetic rat splanchnic nerve stimulation at 16.7 mmol/l glucose decreased insulin secretion (14%) further than in the control rats (30%), however, somatostatin secretion did not decrease to the same extent. Similar results were also observed at the low (1 mmol/l) glucose concentration. On the other hand, percent decreases of insulin and somatostatin secretion induced by splanchnic nerve stimulation in the streptozocin-diabetic rats were similar to the values observed in the normal control rats. The glucagon secretion in response to splanchnic nerve stimulation at 16.7 mmol/l glucose from pancreatic Alpha cells in both types of induced diabetes is exaggerated, and the degree of exaggeration seems to parallel the severity of the hyperglycaemia. However, the splanchnic nerve stimulation-induced glucagon secretion at 1 mmol/l glucose was impaired in the streptozotocin-diabetic rats, but not in the neonatal streptozotocin-diabetic rats. These data suggest that the sensitivity of diabetic Alpha and Delta cells to sympathetic neural activation are blunted, whereas the sensitivity of Beta cells is enhanced in the diabetic animal model.

Animals↗
PubMed1992

Properties of test metal ceramic titanium alloys.

Four test alloys were prepared using a high frequency centrifugal casting machine and a ceramic crucible for the development of titanium bonding alloys that can be cast in the ordinary atmosphere. Of these alloys, 10.06% Ti, 78.79% Ni, 9.02% Pd, 1.77% Sn and 9.91% Ti, 78.56% Ni, 9.07% Pd, 1.86% Sn, 0.65% Ir could be cast by the conventional high frequency centrifugal method; however, 89.18% Ti, 8.75% Ni, 1.03% Pd, 0.28% Sn and 89.81% Ti, 8.15% Ni, 1.01% Pd, 0.18% Sn, 0.67% Ir could be cast only by the argon are melting method. The alloys 10.06% Ti, 78.95% Ni, 9.02% Pd, 1.77% Sn and 9.91% Ti, 78.56% Ni, 9.07% Pd, 1.86% Sn, 0.65% Ir showed excellent physical and mechanical properties and bonding strengths, surpassing those of the commercial alloys TPW and Unimetal. Concerning the elution of component elements, the amounts of titanium eluted from these alloys were far smaller than those from pure titanium or a Ti-6Al-4V alloy, and nickel elution, which has become an issue in relation to metal allergy, was almost nil in contrast to Unimetal (Ni-Cr alloy). The alloy 9.91% Ti, 78.56% Ni, 9.07% Pd, 1.86% Sn, 0.65% Ir showed properties that indicated its favorable use as an alloy for the bonding of dental porcelain.

Adhesiveness↗
PubMed1992

Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion.

Crosslinking HLA-DR molecules by monoclonal antibodies (moAbs) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic calcium concentrations in activated human T cells. Binding of bacterial superantigens or moAbs to DR molecules on activated T cells was recently reported to induce homotypic aggregation through activation of protein kinase C (PKC) and mediated by CD11a/CD54 (LFA-1/CAM-1) adhesion molecules. Here, we report that moAbs directed against framework DR, but neither DR1, 2- and DRw52- nor DQ- and DP-specific moABs induced homotypic aggregation of antigen- and alloantigen-activated T cells, antigen-specific CD4+ T-cell lines, a CD8+ T-cytotoxic cell line, and T-leukemia cells (HUT78). Protein tyrosine kinase (PTK) inhibitor herbimycin A partly blocked class-II-induced aggregation responses. In contrast, phorbol ester (PMA)-induced aggregation was essentially unaffected. A potent inhibitor of PKC, staurosporin, inhibited both moAb- and PMA-induced aggregation responses. The aggregation responses were completely inhibited by low temperatures, cytochalasins B and E, and partly inhibited by EDTA and CD18 moAbs, but unaffected by aphidicolin, mitomycin C, an adenylate cyclase inhibitor (2'5'-dideoxyadenosine), and moAbs against other adhesion molecules (CD2/CD58 [LFA-3], CD28/CD28 ligand B7, CD4, and CD44). In conclusion, HLA class-II-induced aggregation responses in activated T cells appear to involve PTK and PKC activation and to be mediated through CD11a-dependent and independent adhesion pathways.

Alkaloids↗
PubMed1992

Studies on the function mechanism of a Formosan grey mullet protamine-mugiline beta M6: interaction of the M6 and M6 fragments with DNA.

The interaction of three peptide segments of one component of Formosan grey mullet protamine (mugiline beta M6), obtained by chemical and enzymatic cleavage, with DNA was studied by spectroscopic measurement, thermal denaturation and circular dichroism. The data obtained were then compared with those of whole M6 and other fish protamines such as salmine of salmon and clupeine of herring. M6-B-I, which lacks C-terminal 11 amino acids in M6, showed significantly different properties. It showed remarkably high DNA aggregating ability which was due to a conformational change of DNA from B to A form. The conformational change of DNA induced by the binding of M6-B-I was reproduced by the carboxypeptidase B digestion of DNA-M6 complex. From these results, the arginine-rich, C-terminal domain of the M6 molecule was estimated to be essential for natural DNA binding.

Amino Acid Sequence↗
PubMed1992

Fast skeletal myosin isoforms in thermally acclimated carp.

Fast skeletal myosins were isolated from carp acclimated to 10 and 30 degrees C, and their structural and enzymatic properties were compared. Myosins in 0.5 M KCl were subjected to limited proteolysis by using various proteases including alpha-chymotrypsin, trypsin, and papain, and different SDS-PAGE patterns were seen for the 10- and 30 degrees C-acclimated myosins in all cases. Myosin subfragment-1 (S1) prepared from the 10 degrees C-acclimated myosin by alpha-chymotryptic digestion in 0.12 M NaCl showed higher acto-S1 Mg(2+)-ATPase activity and lower thermostability than S1 from the warm-acclimated myosin. The peptide maps and ATP-induced spectral changes of tryptophan fluorescence also showed an obvious difference between the two types of S1. Temperature acclimation further caused changes in the rod region of myosin, since the apparent sizes of light meromyosin were different from each other for the two types of myosin. Myosin from carp acclimated to 20 degrees C showed intermediate properties between those of the 10- and 30 degrees C-acclimated myosins. Myosin isoforms might be expressed in a temperature-dependent manner to compensate for the effect of seasonal environmental temperature variation on swimming ability.

Acclimatization↗
PubMed1992

Beta-sheet folding of fragment (16-36) of bovine pancreatic trypsin inhibitor as predicted by Monte Carlo simulated annealing.

A tertiary structure prediction is described using Monte Carlo simulated annealing for the peptide fragment corresponding to residues 16-36 of bovine pancreatic trypsin inhibitor (BPTI). The simulation starts with randomly chosen initial conformations and is performed without imposing experimental constraints using energy functions given for generic interatomic interactions. Out of 20 simulation trials, seven conformations show a sheet-like structure--two strands connected by a turn--although this sheet-like structure is not as rigid as that observed in native BPTI. It is also shown that these conformations are mostly looped and exhibit a native-like right-handed twist. Unlike the case with the C-peptide of RNase A, no conspicuous alpha-helical structure is found in any of the final conformations obtained in the simulation. However, the lowest-energy conformation does not resemble exactly the native structure. This indicates that the rigid beta-sheet conformation of native BPTI merely corresponds to a local minimum of the energy function if the fragment with residues 16-36 is isolated from the native protein. A statistical analysis of all 20 final conformations suggests that the tendency for the peptide segments to form extended beta-strands is strong for those with residues 18-24, and moderate for those with residues 30-35. The segment of residues 25-29 does not tend to form any definite structure. In native BPTI, the former segments are involved in the beta-sheet and the latter in the turn. A folding scenario is also speculated from this analysis.

Algorithms↗
PubMed1992

Successful autograft with peripheral blood stem cells in a child with T-lymphoblastic leukemia.

Peripheral blood stem cells (PBSC) were collected by two leukaphereses and cryopreserved in a 3-year-old girl with T-lymphoblastic leukemia; this was after remission was induced by an investigative regimen when she failed to respond to a first-line induction therapy. The patient received marrow-ablative chemotherapy 4.5 months after the diagnosis; this was followed by the infusion of thawed PBSC (203 x 10(4) CFU-GM/kg). The peripheral granulocyte count reached 0.5 x 10(9)/L by day +7 and the platelet count reached 20 x 10(9)/L by day + 9. Thereafter, the leukocyte count increased to 38 x 10(9)/L by day +14, with a gradual decline to normal levels. She has remained in unmaintained, complete remission 47 months after the autograft, with full school activity. This case illustrates the PBSC autograft is useful as an alternative to bone-marrow transplantation in a selected patient population, and extends the application of cure-oriented therapy to refractory childhood leukemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Prevention of perinatal transmission of hepatitis B virus carrier state.

By means of passive and active immunization with hepatitis B immunoglobulin and hepatitis B vaccine, 396 of 407 babies born to hepatitis B antigen-positive carrier mothers, were protected from establishing the hepatitis B virus (HBV) carrier state during a follow-up period of 12 months or longer. Four infants developed the HBV carrier state before the completion of the immunoprophylaxis schedule, and another seven developed the state after the completion of the schedule. Seroconversion of anti-HBc was observed in 26.8% of the successfully protected infants. In Japan a nationwide program to prevent the vertical transmission of HBV with these procedures was established in 1986, and so liver diseases due to HBV are expected to be eliminated in the near future.

Carrier State↗
PubMed1992

Detection of genomic sequences of respiratory syncytial virus in otitis media with effusion in children.

The reverse transcriptase-polymerase chain reaction and the nested polymerase chain reaction were used for detection of respiratory syncytial virus (RSV) sequences in middle ear effusions collected from children with otitis media. Sequences of RSV were detected in 21 of 34 samples tested. These samples were collected during and/or after natural outbreaks of RSV infection in the community. In those patients from whose nasopharynges RSV was isolated, the viral sequences were highly detectable (75%) in the effusions. These observations suggest RSV as an important factor in the pathogenesis of otitis media with effusion.

Base Sequence↗
PubMed1992

Effects of naloxone and levallorphan on the spinal cord reflex potentials under the spinal ischemic condition in cats.

The spinal reflex potentials elicited by electrical stimulation of the tibial nerve were recorded from the lumbo-sacral ventral root in spinal cats. When the thoracic aorta and the bilateral internal mammary arteries were occluded for 10 min, the potentials were completely depressed. Reappearance of these potentials could be observed at about 10 min after removal of the occlusion and they gradually recovered. Intravenous injection of naloxone (1 or 10 mg/kg) or levallorphan (0.1 mg/kg) together with removal of occlusion significantly promoted the recovery of the polysynaptic reflex potential. Morphine (5 mg/kg) showed no particular effect on the recovery of potentials. Furthermore, pretreatment with morphine (5 mg/kg) did not influence the effects of these opioid antagonists. These results suggest that naloxone and levallorphan may preserve or potentiate the interneuronal activities of the lumbo-sacral spinal cord under the ischemic condition and that the effects may not be mediated through morphine-like opioid receptors.

Animals↗
PubMed1992

Effect of pancreas transplantation on decreased levels of circulating bone gamma-carboxyglutamic acid-containing protein and osteopenia in rats with streptozotocin-induced diabetes.

Diabetic osteopenia has been known as one of the chronic complications of diabetes mellitus, and a decrease in bone turnover has been thought to be one of the pathophysiological characteristics of this complication. In order to investigate the effect of long-term insulin therapy on low bone turnover in diabetes, pancreas transplantation was performed on streptozotocin-induced diabetic rats. Plasma levels of bone gamma-carboxyglutamic acid-containing protein(osteocalcin) in untreated diabetic rats were 0.9 +/- 0.1 (mean +/- SEM) nmol/l, significantly lower than the value of 4.2 +/- 0.6 nmol/l in control rats (p less than 0.01). Pancreas transplantation reversed this decrease to 6.3 +/- 1.1 nmol/l, which was not significantly different from the value in control rats. The circulating levels of calcitriol were significantly decreased in the untreated diabetic group (p less than 0.01), and the decrease was fully reversed by pancreas transplantation. In addition, the decreases in bone length, strength and weight were also improved by the transplantation. This evidence clearly shows that the improvement of metabolic derangements in diabetes by insulin is essential for the prevention of deterioration in diabetic osteopenia. It is possible, therefore, that insulin exerts an indirect beneficial influence through the metabolic amelioration on the decreases in bone turnover and circulating osteocalcin in diabetes mellitus, or has a direct stimulatory effect on the osteoblasts via the insulin receptor since its presence has been shown recently in osteoblastic cells.

1-Carboxyglutamic Acid↗
PubMed1992

Expression of GLUT1 and GLUT2 glucose transporter isoforms in rat islets of Langerhans and their regulation by glucose.

Previous studies revealed that rat islets express the GLUT2-liver facilitative glucose transporter isoform, a glucose carrier with a low affinity for glucose but a high capacity for glucose transport. These studies indicated the presence of a second glucose transporter in rat islets; however, they did not indicate to which of the five known facilitative glucose transporters it corresponded. In this study, we isolated RNA from rat islets of Langerhans and confirmed the presence of GLUT2 mRNA. In addition, we present data indicating that the second isoform expressed in islets is the GLUT1-erythrocyte isoform. The effect of culturing islets in 5.5, 8.3, or 11.1 mM glucose on the levels of GLUT1 and GLUT2 mRNA also was examined. The levels of GLUT1 and GLUT2 mRNA were two- and threefold higher, respectively, in islets cultured for 24 h in 11.1 mM glucose compared with those incubated in the presence of 5.5 mM glucose. Therefore, the previously observed increase in GLUT2 mRNA levels in the islets of rats made hyperglycemic by chronic infusion of glucose can be mimicked in vitro, implying that glucose regulates GLUT2 mRNA expression.

Animals↗
PubMed1992

Role of cytosolic Ca2+ in impaired sensitivity to glucose of rat pancreatic islets exposed to high glucose in vitro.

Sustained exposure to high concentrations of glucose selectively impairs the ability of pancreatic islets to secrete insulin in acute glucose stimulation. In order to evaluate the interrelationship between impaired insulin secretion and the dynamics of the cytosolic free Ca2+ level ([Ca2+]i), we have investigated the effect of high glucose exposure on both [Ca2+]i dynamics in single rat beta-cells and insulin release from rat pancreatic islets. Islets cultured at a high glucose concentration (16.7 mM) for 24 h showed significant reductions of the 16.7 mM GSIR compared with islets cultured at a normal glucose concentration (5.5 mM) (3.38 +/- 0.24 vs. 4.26 +/- 0.34%, respectively, P < 0.05). The capacity of glucose to raise the [Ca2+]i level also was significantly reduced in the beta-cells maintained for 24 h at 16.7 mM glucose (P < 0.001). An additional culture in the medium with 5.5 mM glucose for 16 h restored both the GSIR and the [Ca2+]i response of islets cultured at high glucose. On the other hand, insulin release and [Ca2+]i rise in response to 20 mM L-Arg were well preserved. These observations confirm that exposure of pancreatic beta-cells to high glucose concentrations induces a selective reduction of the GSIR and, further, shows that this impaired response is reversibly restored by an additional culture with normal glucose. We also suggest that the inability of glucose to provoke a [Ca2+]i rise, which is observed in the beta-cells exposed to high glucose, may be responsible for the selective impairment of the GSIR.

Animals↗