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Biomedical subjects

K Okuda

Publications and source records attributed to K Okuda.

At least 145 records · Page 8Linked to original sources

Adsorption of oral bacteria to porous type calcium carbonate.

The purpose of this study was to investigate the adsorption of [3H]-thymidine labeled oral microorganisms to porous type calcium carbonate (PCC) beads in a buffer containing human parotid saliva and to PCC combined chewing gum sheets. Adsorption rates of Streptococcus sobrinus B13 and 6715, Streptococcus mutans MT8148R and Actinomyces naeslundii T14V with PCC were significantly higher than those with calcium carbonate (CC) beads (p < 0.01). Adsorption rates of S. sobrinus, S. mutans and A. naeslundii with PCC combined chewing gum were significantly higher than those with CC combined chewing gum (p < 0.01). The present results suggested that the chewing gum containing PCC may be able to exclude oral bacteria, including cariogenic and periodontopathic bacteria, for prevention of dental caries and periodontal disease.

Actinomyces↗

Differences in TNF-alpha producing activity from murine peritoneal macrophages induced by lipopolysaccharides of Prevotella heparinolytica and Porphyromonas gingivalis.

We compared the effects of LPSs from P. gingivalis and P. heparinolytica on the induction of tumor necrosis factor-alpha (TNF-alpha) production by murine peritoneal macrophages. The lipopolysaccharide (LPS) preparation from P. gingivalis showed a typical ladder pattern in SDS-PAGE, whereas that from P. heparinolytica formed several stained bands without a ladder pattern. When the macrophages from C3H/HeJ mice were incubated with P. gingivalis LPS, the level of TNF-alpha released in the culture supernatants was significantly higher than that with P. heparinolytica. All tested reagents except genistein strongly inhibited the production of TNF-alpha by the macrophages after induction by either LPS. These results suggested the following possibilities, i) the induction level of TNF-alpha by P. heparinolytica is similar to that of Salmonella minnesota, ii) tyrosine phosphorylation is not the only pathway for the TNF-alpha production induced by these LPSs, iii) different regulatory mechanisms are involved in TNF-alpha production in P. gingivalis LPS stimulated and P. heparinolytica LPS stimulated cells.

Animals↗

A case of synchronous double cancers of the pancreas and stomach.

Pancreatic cancer carries a poor prognosis, especially invasive ductal carcinoma of the pancreas. We present here the case of a 76-year-old man who developed synchronous double cancers of the stomach and pancreas. He was referred to our hospital in December, 1997, with a provisional diagnosis of carcinoma of the stomach. Laboratory data on admission showed normal levels except for the serum carcinoembryonic antigen level. Abdominal ultrasonography revealed a low echoic mass anterior to the pancreas, suggestive of a nodal metastasis. Intraoperative histological findings from the pancreatic nodule confirmed a primary pancreatic cancer. The diagnosis of double cancers of the stomach and pancreas was made, and subtotal gastrectomy and distal pancreatectomy with lymph nodes dissection were carried out. The histologic sections from the stomach showed a moderately differentiated tubular adenocarcinoma, whereas those from the pancreas showed a well to moderately differentiated tubular adenocarcinoma. Double carcinomas in this association are relatively rare.

Aged↗

[Indication and limitation of microwave coagulation therapy for stage IV-A hepatocellular carcinoma].

Patients with stage IV-A hepatocellular carcinoma have been considered to have dismal prognosis. However, among them there are many of patients with multiple carcinoma of multicentric origin, whose prognosis is not necessarily poor. For treatment of multiple carcinoma, preoperative evaluation for the malignant aggressiveness of each nodule, and for liver function impairment is essential. Although hepatic resection has a high curability, resection sometimes impair long term survival because of postoperative deterioration of liver function. In this point, heat ablation therapy such as microwave coagulation therapy is favorable treatment, and for some nodules at early stage heat ablation therapy would have a sufficient curability to achieve long term survival. Authors decide on the selection of treatment (resection or heat ablation therapy) according to preoperative evaluation for the malignant aggressiveness by diagnosis of tumor gross type, and for the degree of liver impairment by serum hyaruronic acid level.

Adult↗

Molecular pathogenesis of the cell surface proteins and lipids from Treponema denticola.

Treponema denticola, frequently isolated from the human oral cavity, is thought to be a major pathogen of human periodontal disease. Recent developments in molecular analysis have clarified the surface structure of this microorganism and the characteristics of its pathogenic factors. Structural analysis of the outer sheath showed T. denticola to have a new type of outer membrane lipid. Limited exposure of the major outer sheath protein is suggested by electron-microscopic analysis. A protease-deficient mutant has revealed the roles of the protease in the organization of the outer sheath material and in T. denticola pathogenicity. The surface features that contribute to the pathogenicity of T. denticola in periodontal disease are gradually being elucidated, and are reviewed.

Bacterial Adhesion↗

Evidence of HIV type 1 glycoprotein 120 binding to recombinant N-methyl-D-aspartate receptor subunits expressed in a baculovirus system.

Activation of the N-methyl-D-aspartate (NMDA) receptor by HIV-1 envelope glycoprotein 120 (gp120) is thought to represent at least one of the pathways causing neuronal damage in AIDS patients. In the present study, recombinant gp120 binding to NMDA receptor subunits expressed in a baculovirus system was examined by immunocytochemistry and a binding assay, using horseradish peroxidase (HRP)-conjugated and 125I-labeled recombinant gp120, respectively. We found that recombinant gp120 binds to Sf21 cells expressing epsilon1/zeta1 or epsilon2/zeta1 combined NMDA receptor subunits, but not to Sf21 cells infected with mock virus or Sf21 cells expressing a single epsilon1, epsilon2, or zeta1 NMDA receptor subunit. The binding was strongly blocked by unlabeled recombinant gp120, monoclonal anti-HIV-1 gp160 antibody, and a mixture of anti-epsilon1/epsilon2 and anti-zeta1 antibodies. The same results were obtained by flow cytometric analysis. These data suggest that HIV-1 gp120 may directly bind to the NMDA receptor. This evidence enhances our understanding of the mechanism of HIV-1-induced neuronal damage in AIDS patients.

Animals↗

Inhibition of E. coli growth by fullerene derivatives and inhibition mechanism.

Cationic ammonium fullerene derivatives (C60-bis(N, N-dimethylpyrrolidinium iodide) and C60-bis(N-methylpiperazinium iodide)) suppressed E. coli growth, whereas an anionic derivative (C60-dimalonic acid) did not. Both cationic derivatives inhibited E. coli dioxygen consumption. Inhibition of energy metabolism is concluded to be a mechanism of the growth inhibition effect of fullerene derivatives.

Anti-Bacterial Agents↗

Independent evolution of HIV type 1 in different brain regions.

HIV-1-associated brain pathology exhibits regional variability and we therefore studied the genetic differences in the V1-V5 domains of the HIV env gene in up to four regions of brain (frontal lobe, basal ganglia, medial temporal lobe, and nonmedial temporal lobe) from three patients. We found that in each separate brain region HIV-1 forms different quasispecies and that there is little gene flow among these regions. In further support of brain region-specific evolution of HIV-1, we analyzed amino acid signatures in these clones. In addition to known amino acid signatures associated with macrophage tropism and the lack of syncytium formation, we found 15 majority amino acid signature patterns from the V1-V5 env sequences associated with the neuroanatomical regions analyzed from the three individuals. Furthermore, on average, intrabrain genetic distances for the HIV-1 env were estimated to be much smaller than genetic distances between brain regions. Specific strains of HIV-1 may be neurotropic or neuroinvasive (replication preference in brain tissue) and may contribute to pathology, cognitive loss, and neuropsychiatric disease.

Adult↗

Signaling domains of the beta c chain of the GM-CSF/IL-3/IL-5 receptor.

The granulocyte/macrophage colony-stimulating factor (GM-CSF)/interleukin-3 (IL-3)/IL-5 receptors are a family of heterodimeric transmembrane proteins expressed by myeloid lineage cells. Each receptor has a unique ligand-binding alpha chain and they share a common beta chain (beta c chain). Binding of GM-CSF activates at least one receptor-associated tyrosine kinase, JAK2, and rapidly induces tyrosine phosphorylation of the GMR beta c chain (GMR beta), but not the GMR alpha chain (GMR alpha). Mutation of each of the 8 tyrosine residues in the cytoplasmic domain of the human GMR beta to phenylalanine (GMR beta-F8) reduced tyrosine phosphorylation of GMR beta, SHP2 and SHC, but not JAK2 or STAT5. Interestingly, GMR beta-F8 was still capable of inducing at least short-term proliferation and enhancing viability. The role of each individual tyrosine residue was explored by replacing each mutated phenylalanine with the wild-type tyrosine residue. Tyrosine 577 was found to be sufficient to regenerate GM-CSF-dependent phosphorylation of SHC, and any of Y577, Y612, or Y695 were sufficient to regenerate GM-CSF-inducible phosphorylation of SHP2. Next, a series of four internal deletion mutants were generated, which deleted small sections from aa 518 to 626. One of these, deleting residues 566-589 was profoundly defective in signaling and supporting viability, and may identify an important viability signaling domain for this receptor family. Overall, these results indicate that GMR beta tyrosine residues are not necessary for activation of the JAK/STAT pathway, or for proliferation, viability, or adhesion signaling in Ba/F3 cells, although tyrosine residues significantly affect the magnitude of the response. However, internal deletion mutant studies identify critical domains for viability and proliferation.

Amino Acid Substitution↗

Administration of an IL-12-encoding DNA plasmid prevents the development of chronic graft-versus-host disease (GVHD).

The transfer of DBA/2 spleen cells into (C57BL/10 x DBA/2)F1 mice induces chronic graft-vs-host disease (GVHD), which is characterized by the production of Th2 cytokines, hypergammaglobulinemia, and immune complex-mediated glomerulonephritis like systemic lupus erythematosus. IL-12 strongly induces the production of Th1 cytokines and reduces Th2 activity in vivo. In this study, the effect of gene therapy on the development of murine chronic GVHD was examined using an IL-12-encoding plasmid (pCAGGSIL-12), with the expectation that it might regulate Th1/Th2 activity and have a beneficial impact on the clinical manifestations of disease. pCAGGSIL-12 or its p40 antagonist plasmid (pCAGGSp40) were injected i.m. every 3 wk in GVHD-induced (C57BL/10 x DBA/2)F1 mice. A total of 100 microg of pCAGGSIL-12 improved the Th1/Th2 balance in vivo, suppressed the production of IgG, and significantly reduced the development of glomerulonephritis. GVHD was exacerbated by injection of the pCAGGSp40 antagonist. Our results demonstrate that GVHD can be treated successfully by the administration of an IL-12-encoding plasmid, and that such therapy does not induce acute GVHD.

Animals↗

IL-15 expression plasmid enhances cell-mediated immunity induced by an HIV-1 DNA vaccine.

Cytokines are powerful regulators of the immune response. In this study, an HIV-1 envelope DNA vaccine and interleukin 15 (IL-15) expression plasmid were intranasally administered to mice. A significant increase in the HIV-1-specific DTH response and CTL activity, and decrease in the serum IgG/IgG2a ratio was observed in the group which received DNA vaccine and IL-15 expression plasmid compared to DNA vaccination alone. Restimulated immune lymphoid cells from mice which received both agents showed enhanced production of interferon-gamma (IFN-gamma) and reduced secretion of IL-4. However, administration of DNA vaccine with IL-15 and IL-2 or IL-12 expression plasmids did not alter the effect of IL-15 expression plasmid on the DNA vaccine. These results indicate that intranasal administration of DNA vaccine and IL-15 expression plasmid is capable of enhancing the T helper type 1 (Th1) dependent HIV-1-specific cell-mediated immunity, and that the IL-15 and IL-2 or IL-12 expression plasmids may not have a synergistic effect on the immune response induced by DNA vaccine in vivo.

Adjuvants, Immunologic↗

Altered vasoreactivity to angiotensin II in experimental diabetic neuropathy: role of nitric oxide.

We evaluated the effects of angiotensin II and an angiotensin-converting enzyme inhibitor (cilazapril) on nerve blood flow (NBF) and electrophysiology in control and diabetic rats. When applied locally to the sciatic nerve, the dose-response curve of angiotensin II was more potent in experimental diabetic neuropathy (EDN) than control rats. No difference existed in plasma angiotensin II levels between EDN and controls. The rats were given typical rat pellets or pellets treated with 10 mg/kg per day cilazapril for 4 weeks. Diabetes caused a significant reduction in NBF, nerve conduction velocity, and compound muscle action potential (CMAP) amplitudes. NBF was significantly increased in diabetic rats supplemented with cilazapril diet, and nerve conduction velocity and amplitudes of the CMAP were also improved after 4 weeks on this diet. Direct application 10(-3) mol/L cilazapril on sciatic nerve did not increase NBF in normal and EDN rats. We topically applied the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine, on sciatic nerve and observed reduced inhibition of NBF in EDN, which was correctable with a cilazapril diet. These results suggest that diabetic neuropathy may have an increasing vasopressor action with angiotensin II and this is likely to be the mechanism of NOS inhibition. Angiotensin II-converting enzyme inhibitors may have potential in the treatment of diabetic neuropathy.

Angiotensin II↗

Proposed standard for human blood vitamin B1 value using HPLC. The Committee for Vitamin Laboratory Standards, Japan.

Standard reference ranges for all laboratory test values are mandatory. This study was designed to establish a reference range for blood vitamin B1 levels, since the normal range has not been determined in the Japanese population. We founded the Japan Committee for Vitamin Laboratory Standards, which was incorporated with the Vitamin Society of Japan and the Japanese Society of Nutrition and Food Science. We standardized whole blood vitamin B1 levels using three HPLC techniques (post-column reverse-phase HPLC, pre-column reverse-phase HPLC, and precolumn GP-HPLC). The reference range was obtained in 54 volunteers administered a 1,800 kcal diet with 2 mg of vitamin B1 (1.74 mg measured) daily to avoid marginal vitamin B1 deficiency in the population. The range for each assay was 26-47, 28-51, and 28-56 ng/ml, respectively. Our data suggest that 26-28 ng/ml is the lower limit of normal for whole blood vitamin B1, but further studies in a larger population are needed in order to obtain more definitive results.

Chromatography, High Pressure Liquid↗

Propensity of ectopic liver to hepatocarcinogenesis: case reports and a review of the literature.

Two patients with ectopic liver are described. In one patient, a small ectopic liver attached to the gastric serosa developed hepatocellular carcinoma (HCC). The preoperative diagnosis was an alpha-fetoprotein (AFP)-producing carcinoma and a malignant ulcer of the stomach. Total gastrectomy and esophago-jejunostomy were performed. The tumor that measured 4 x 2 x 2 cm contained an AFP-producing HCC and normal liver tissue. In another patient who had alcoholic cirrhosis, ectopic liver on the serosa of the gallbladder was found to have the same histological changes as the mother liver. A survey of the literature disclosed more than 20 cases in which HCC developed outside the liver; the liver did not have HCC. By contrast, there was only one report on HCC occurring in the liver in the presence of a noncancerous, relatively large accessory liver lobe. Because ectopic liver does not have a complete vascular and ductal system as a normal liver, it is perhaps functionally handicapped and more prone to hepatocarcinogenesis.

Carcinoma, Hepatocellular↗

Immunization of RANTES expression plasmid with a DNA vaccine enhances HIV-1-specific immunity.

Cytokines play important roles in regulating immune response. This study evaluated the adjuvant effect of an expression plasmid encoding RANTES (regulated on activation normal T-cell expressed and secreted) chemokine on the immunity induced by a DNA vaccine. This vaccine consists of expression plasmids encoding the env and rev genes of human immunodeficiency virus type 1 (HIV-1). DNA vaccination with RANTES plasmid induced significantly higher titers of serum HIV-1-specific IgG and IgG2a antibodies than DNA vaccination alone on both intramuscular and intranasal immunization. This combination also increased HIV-1-specific cytotoxic T lymphocyte activity and delayed-type hypersensitivity. Intranasal immunization induced a higher titer of fecal secretory IgA antibody than intramuscular immunization. These results demonstrate that coadministration of RANTES plasmid dominantly induced HIV-1-specific cell-mediated immunity.

Adjuvants, Immunologic↗