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Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 865 records · Page 48Linked to original sources

Phenotype and ontogeny of cells carrying a tumor-associated antigen that is expressed on bovine leukemia virus-induced lymphosarcoma.

The phenotype and ontogeny of cells carrying the tumor-associated antigen (TAA), identified in tumors of cattle with enzootic bovine leukosis (EBL) by use of the monoclonal antibody (MAb) c143, were analyzed by flow cytometry and immunohistochemistry. The TAA recognized by the c143 MAb (c143 TAA) was mainly expressed on B-cells, macrophages, reticular cells, and a minor population of BoCD4-positive T-cells in bovine leukemia virus (BLV)-free normal cattle. When the peripheral blood mononuclear cells from normal cattle were activated in vitro, some populations of BoCD8-positive T- and non-T/non-B-cells also showed expression. Moreover, B-cells expressed the c143 TAA until the antigen was lost from cells at the final stage of B-cell differentiation, namely, the plasma cell stage. The c143 MAb-positive cells in blood of BLV-free normal cattle form heterologous subpopulations, and these cells coexpress other surface markers such as BoCD2, BoCD5, BoCD6, and B-cell-specific molecules B1 low, B1 bright, and B2. In BLV-infected cattle, the proportion of peripheral blood mononuclear cells that express the c143 TAA increased with the progression of EBL, and, in addition, BLV-infected cattle that had no lymphosarcomas showed increased proportions of c143 MAb-positive cells that coexpressed surface IgM (sIgM), BoCD5, B1 low, and B2 but not BoCD2, BoCD4, or BoCD6. Furthermore, most of the c143 MAb-positive tumors from all cattle with EBL appeared to be a monoclonal population derived from a single B-cell and to be divided into two types, c143 TAA+BoCD5+B1 low+ B2+ sIgM+ or sIgM-. Collectively, these results show that the c143 TAA is not only a useful surface marker for identification of EBL but also a marker of differentiation of lymphoid cells.

Animals↗

Pharmacokinetics, safety, and pharmacologic effects of OPC-21268, a nonpeptide orally active vasopressin V1 receptor antagonist, in humans.

The pharmacokinetics, safety, and pharmacologic effects of OPC-21268, a nonpeptide orally active vasopressin V1 receptor antagonist, have been investigated in 33 healthy subjects. First, 24 subjects were randomly divided into 3 groups of 8, 6 of whom were given 2 ascending single oral doses out of 6 (10, 50, 150, 300, 450, and 600 mg) of OPC-21268 after an overnight fast. The remaining two subjects in each group received placebo as control at each dosing. Additionally, after this procedure, the 6 subjects who received 50-mg single doses were given the same dose in a nonfasting condition. After the single-dose study was completed and the safety and tolerability were ascertained, the remaining 9 subjects, including 3 controls, were given 300 mg of the drug 3 times daily for 7 days (days 3-9) and were given single 100-mg oral doses before (day 1) and after (day 10) this repeated-dose study. OPC-21268 plasma concentrations declined in a monoexponential or biexponential pattern after reaching the maximum plasma concentrations (Cmax). The mean (+/- standard error of the mean) plasma half-life (t1/2) of the alpha phase ranged from 1.31 +/- 0.11 to 1.78 +/- 0.15 hours, and the mean t1/2 of the beta phase ranged from 4.31 +/- 0.28 to 6.28 +/- 0.59 hours. The area under the concentration (AUC0-infinity) and Cmax were proportional to the dose (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Frequent isolation of human herpesvirus 7 from saliva samples.

Human herpesvirus 7 (HHV-7) was isolated frequently from saliva specimens. The isolation rates were 81% (13/16) in adults, 70% (7/10) in children over 1 year old, and none (0/7) in children less than 1 year old, respectively, indicating that infection of HHV-7 occurs during early infancy and the virus shedding rate after infection is very high. Human herpesvirus 6 (HHV-6) was not isolated from saliva specimens although some studies on isolation of HHV-6 from saliva was reported previously.

Adult↗

Fibrolamellar hepatocellular carcinoma coexistent with a hepatocellular carcinoma of common type: report of a case.

A case of small fibrolamellar hepatocellular carcinoma (HCC) coexistent with a HCC of common type is herein reported. A 56-year-old man was diagnosed as having multi-nodular type HCC with liver cirrhosis. The serum alpha-fetoprotein (AFP) level was slightly increased. The patient underwent a partial caudate lobectomy and lateral segmentectomy. Histologically, both resected tumors were small HCCs measuring less than 2 cm in diameter. One was a fibrolamellar type located in the caudate lobe, while the other was the common type in the lateral segment of the liver. Positive immunohistochemical staining for AFP was observed in the tumor cells of the HCC of common type but was not observed in the fibrolamellar HCC. We also reviewed previously reported cases of fibrolamellar HCC in Japan, and discussed the clinicopathologic implications of this disease.

Carcinoma, Hepatocellular↗

Basic fibroblast growth factor-like immunoreactivity in the rat trigeminal sensory system and peri-oral skin with vibrissae.

We have characterized an antiserum against basic fibroblast growth factor (bFGF) by immunoblot, investigated the location of bFGF-like immunoreactivity (bFGF-IR) in the trigeminal sensory system and perioral skin endowed with vibrissae, and demonstrated the site of bFGF mRNA expression in the vibrissae by in situ hybridization histochemistry. Light-microscopic immunohistochemistry has demonstrated that bFGF-IR is present not only in trigeminal ganglion neurons and their central and peripheral processes, but also in cells of the matrix, external root sheath and papillae of vibrissae and the stratum basale of the stratified squamous epithelium of the skin. Electron microscopy has revealed intense bFGF-IR mainly in cytoplasmic regions, other than the lumen of rough endoplasmic reticulum and the Golgi apparatus, in trigeminal ganglion neurons, in fibroblast-like cells in the papillae, and in capsules of vibrissae. In contrast, actively proliferating and/or differentiating cells in the matrix of vibrissae have intensely stained euchromatin and weakly labeled cytoplasm that, unlike that of the aforementioned cells, contain immunoreaction products in discrete spots less than 100 nm in diameter, implying the generation of different molecular forms of bFGF in cells of the matrix and papillae. Moreover, the accumulation of bFGF in the euchromatin appears to take place in cells at non-mitotic stages (possibly interphases), characterized by a conspicuous nucleolus and well-developed nuclear envelope. A digoxigenin-labeled cRNA probe for the demonstration of bFGF mRNA gives conspicuous hybridization signals mainly in the matrix of vibrissae. These findings suggest that bFGF is involved in the growth and differentiation of matrix cells during certain periods of the cell cycle and that it acts as a non-mitogenic mediator in the adult trigeminal sensory system.

Animals↗

Induction of cytolytic activity of lymphocytes from carcinomatous pleural effusion by IL-2 and autologous tumor cells.

We established a cell line (STKM-1) from tumor cells obtained from carcinomatous pleural effusion of a gastric cancer patient. The lymphocytes separated from her peripheral blood or pleural effusion were cryopreserved and immunological experiments were performed after the establishment of the cell line. They were treated with IL-2 or with both IL-2 and mitomycin C (MMC)-treated autologous STKM-1 cells. The cytolytic activity against STKM-1 cells was elevated in lymphocytes cultured with IL-2, and was more prominently augmented in lymphocytes cultured with both IL-2 and MMC-treated STKM-1 cells. The elevation in cytolytic activity was more marked with pleural effusion lymphocytes than with the peripheral blood lymphocytes. The results suggest that the lymphocytes obtained from the pleural effusion would be an excellent source for adoptive immunotherapy.

Adenocarcinoma, Scirrhous↗

PI*S(iiyama), a deficiency gene of alpha 1-antitrypsin: evidence for the occurrence in western Japan.

An alpha 1-antitrypsin deficiency associated with pulmonary emphysema was investigated in a 32-year-old Japanese male. Polymerase chain reaction (PCR)-amplified fragments and dot blot hybridization with allele-specific oligonucleotide probes revealed that the patient was homozygous for a C to T transition at codon 53, resulting in the substitution of Phe53 for Ser53 (PI*S(iiyama)). Crossed immunoelectrophoresis after isoelectric focusing and agarose gel electrophoresis showed atypical banding patterns. PI*S(iiyama) is a rare deficiency gene, but it can occur sporadically all over the Japan.

Adult↗

Elevation of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin 8 and 6 in reperfusion injury.

Myocardial ischaemia is one of the major causes of low output syndrome during open heart surgery. Injury associated with ischaemia and reperfusion has been considered to result, in part, from the action of neutrophils, the interaction of neutrophils with vascular endothelial cells, and the effects of cytokines which are mediators that induce and modify reactions between these substances. We investigated cell injury in relation to the concentrations of interleukins 6 and 8 (IL-6 and IL-8), which have recently received attention as neutrophil activators. Neutrophil counts, granulocyte elastase (GEL), IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha), CK, and CK-MB concentrations were determined serially in 11 patients undergoing open heart surgery with cardiopulmonary bypass (CPB). Neutrophil counts (mean +/- SD 2717 +/- 2421 microliters-1 preoperatively) peaked 60 min after declamping the aorta at 7432 +/- 4357 microliters-1 (P < 0.01) and remained elevated 7136 +/- 5194 microliters-1 at 180 min (P < 0.01). Plasma GEL level (168 +/- 71 micrograms.L-1 preoperatively) peaked at 1134 +/- 453 micrograms.L-1 120 min after declamping of the aorta (P < 0.01) and remained elevated, 1062 +/- 467 micrograms.L-1, after 180 min (P < 0.01). Serum IL-6 level (118 +/- 59 pg.ml-1 preoperatively) peaked at 436 +/- 143 pg.ml-1 60 min after declamping of the aorta (P < 0.01) and remained elevated, 332 +/- 109 pg.ml-1, after 180 min. Serum IL-8 level (37 +/- 44 pg.ml-1 preoperatively) peaked at 169 +/- 86 pg.ml-1 at 60 min after declamping of the aorta (P < 0.001) and remained elevated at 113 +/- 78 pg.ml-1 180 min after declamping of the aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Successful resection of a recurrent leiomyosarcoma of the pulmonary trunk.

We successfully performed a total resection of the pulmonary artery trunk and replaced it with an equine pericardial xenograft roll in a patient with a recurrent leiomyosarcoma. We believe, based on anatomic and embryologic principles, total rather than partial resection of the pulmonary artery trunk should be the treatment of choice for primary leiomyosarcomas of the pulmonary artery.

Aged↗

Inhibition by N-ethylmaleimide of H(+)-ATPase reduces the cellular action of arginine vasopressin in cultured rat renal papillary collecting tubule cells.

We examined whether H(+)-ATPase is involved in the control of cellular action of arginine vasopressin (AVP) to produce adenosine 3', 5'-monophosphate (cAMP) and mobilize cellular free calcium ([Ca2+]i) in rat renal papillary collecting tubule cells in culture. N-Ethylmaleimide (NEM), an inhibitor of H(+)-ATPase, reduced the cellular pH (pHi) dose-dependently. AVP increased cellular cAMP production in a dose-dependent manner. 5 x 10(-6) and 1 x 10(-5) M NEM significantly diminished the AVP-induced increase in cAMP production. 1 x 10(-7) M AVP also increased [Ca2+]i from 111.2 to 189.3 nM, which was significantly reduced by NEM in a dose-dependent manner. These results indicate that H(+)-ATPase participates the cellular action of AVP mediated via the pHi control in renal papillary collecting tubule cells.

Animals↗

Antigenic regions defined by monoclonal antibodies on tumor-associated antigens of bovine leukemia virus-induced lymphosarcoma cells.

Tumor-associated antigens (TAAs) expressed on enzootic bovine leukosis tumors were divided previously into three types by use of 13 monoclonal antibodies (MAbs): common TAA, partially common TAA and individually distinct TAA. Since MAb-defined epitopes on the common TAA were conserved on both soluble TAA prepared from bovine B-lymphoma cells and untreated viable same cells, all the MAbs that bound to the soluble TAA also bound to untreated viable cells. By contrast, MAb-defined epitopes on the partially common and individually distinct TAAs varied according to the test systems used. Two of seven MAbs were found to bind to both the soluble TAA and viable cells and one MAb bound to the soluble TAA but not to the viable cells.

Animals↗

Immunohistological study on bovine small intestine including gut associated lymphoid tissue using monoclonal antibodies to WC1, TCR1 and BoCD3.

Selected antibodies (mAbs) that clustered in temporary cluster TC22 (WC1) and TC36 (TCR1) and one unclustered mAb thought to detect BoCD3 were used to compare the distribution of T and B cells and subpopulations of WC1+ or TCR1+ cells in fetal, calf, and young adult gut associated lymphoid tissue. Cells putatively positive for BoCD3 (MM1A) were detected in the interfollicular tissue similar to the pattern noted for BoCD2+ or BoCD5+ cells. WC1+ or TCR1+ cells were detected in small numbers in follicles and interfollicular tissue. Numerous WC1+ or TCR1+ cells were evident in the lamina propria and epithelia, with the highest frequency evident in tissues from animals 8 months of age.

Animals↗

Immunization of institutionalized asthmatic children and patients with psychomotor retardation using live attenuated cold-adapted reassortment influenza A H1N1, H3N2 and B vaccines.

Live attenuated cold-adapted reassortant (CR) influenza virus vaccines were evaluated in institutionalized asthmatic children and severe psychomotor-retarded (SPR) patients. Almost all the vaccinees were seropositive to the vaccine strains before immunization. Trivalent CR vaccine (containing A H1N1 (CR-125), A H3N2 (CR-149) and B (CRB-117)), bivalent CR vaccine (CR-125 and CR-149) and monovalent CRB-117 were inoculated to 19 asthmatic children and 36 and 16 SPR patients, respectively. Overall 49, 22, and 11% of vaccinees were infected by A H1N1, A H3N2 or B vaccine viruses, respectively, as indicated by significant haemagglutination-inhibition (HI) antibody titre rises 4 weeks after inoculation. No severe adverse reactions associated with CR vaccination were observed in the handicapped patients. A nosocomial outbreak of influenza A H1N1 occurred in the ward with asthmatic children, but none of the 19 CR-trivalent vaccinees became infected. However, five of 20 non-vaccinees in the same ward, and ten of 30 vaccinees in another ward that received inactivated split vaccine became infected. The CR vaccines demonstrated significant protective effects against natural exposure to the A H1N1 virus, and were well tolerated and safe when given to patients with bronchial asthma and severe psychomotor retardation.

Adolescent↗

Comparing the cell population on different intraocular lens materials in one eye.

We developed a method to evaluate cell adherence to different intraocular lens (IOL) materials in one eye in which we coated one half of the anterior surface of a poly(methyl methacrylate) (PMMA) IOL with poly(dimethyl siloxane), a silicone material. The lenses were implanted in the anterior chamber of rabbit eyes without lens extraction. Postoperative cellular reaction on the IOL surfaces was studied by specular microscopy. The IOLs were fixed in situ, removed from the eyes, and stained with hematoxylin-eosin so we could evaluate the cell population on the silicone and PMMA surface. Fewer cells were scattered on the silicone surface than on the PMMA surface. This method excludes surgical effects and allows a comparison of various IOL materials in the same eye.

Animals↗

Therapeutic efficacy of non-peptide ADH antagonist OPC-31260 in SIADH rats.

The present study was undertaken to determine whether the non-peptide V2 antidiuretic hormone (ADH) antagonist 5-dimethylamino-1[4-(2- methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (OPC-31260) normalized hyponatremia in rats with an experimental syndrome of inappropriate secretion of ADH (SIADH). Rats were administered V2 agonist 1-deamino-8-D-arginine vasopressin (dDAVP) subcutaneously at a rate of 5 ng/hr using an osmotic minipump and a 40 ml/day liquid diet. Serum sodium levels (SNa) and serum osmolality (SOsm) markedly decreased to 119 mEq/liter and 249 mOsm/kg H2O, respectively, 48 hours after the start of dDAVP administration. Hyponatremia persisted in a similar magnitude during the observation period of 14 days. On days 7 to 13 OPC-31260, administered 5 mg/kg per day orally, promptly raised SNa and SOsm to 134 mEq/liter and 282 mOsm/kg H2O in half a day, respectively, followed by the normalization of SNa and SOsm during the rest of the observation period. The cease of administration of OPC-31260 again decreased SNa and SOsm in rats receiving dDAVP. In contrast, SNa and SOsm were within the normal values in rats receiving 0.15 M NaCl, a vehicle for dDAVP, in the presence or absence of OPC-31260. The administration of OPC-31260 promptly caused marked water diuresis on day 7 in the hyponatremic rats receiving dDAVP, namely 5 mg/kg OPC-31260 markedly increased urinary volume and decreased UOsm. These results indicate that there is dilutional hyponatremia in rats receiving dDAVP and 40 ml/day liquid diets, and that OPC-31260 is an effective therapeutic for hyponatremia associated with dDAVP-induced SIADH.

Animals↗

Enhancement of vascular action of arginine vasopressin by diminished extracellular sodium concentration.

The present study was undertaken to examine the effects of diminished extracellular sodium concentration on the vascular action of arginine vasopressin (AVP) in cultured rat vascular smooth muscle cells (VSMC). The preincubation of cells with the 110 mM extracellular Na+ ([Na+]e) solution supplemented with 30 mM choline chloride for 60 minutes enhanced the effect of AVP- (1 x 10(-8) M) induced VSMC contraction. The treatment of 110 mM [Na+]e solution also enhanced the cellular contractile response to the protein kinase C (PKC) activators, phorbol 12-myristate 13-acetate and 1-oleoyl-2-acetyl-glycerol. Furthermore, preincubation with the 110 mM [Na+]e solution also potentiated the effect of 1 x 10(-8) M AVP, but not 1 x 10(-6) M, to increase the cytosolic-free Ca2+ ([Ca2+]i) concentration. The 110 mM [Na+]e media decreased the basal intracellular Na+ concentration and increased intracellular 45Ca2+ accumulation, basal [Ca2+]i and AVP-produced 45Ca2+ efflux. These effects of 110 mM [Na+]e solution to enhance the vascular action of AVP were abolished by using Ca(2+)-free 110 mM [Na+]e solution during the preincubation period. The preincubation with the 110 mM [Na+]e solution did not change either the Kd and Bmax of AVP V1 receptor of VSMC or the AVP-induced production of inositol 1,4,5-trisphosphate. The present in vitro results therefore indicate that the diminished extracellular fluid sodium concentration within a range observed in clinical hyponatremic states enhances the vascular action of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in pH affect Cl- removal and AVP action in collecting tubules.

We examined what mechanisms are involved in the alteration by chloride (Cl-) removal of arginine vasopressin (AVP)-induced cellular cAMP production, and cellular free calcium ([Ca2+]i) mobilization in rat renal papillary collecting tubule cells in culture, using two buffer systems: bicarbonate and non-bicarbonate buffers. The first study was performed in the bicarbonate-supplemented buffer. Removal of Cl-, which was replaced by methylsulfonate or gluconate, increased cellular pH (pHi) from 7.19 to 7.26. AVP increased cellular cAMP production in a dose-dependent manner; 1 x 10(-9) and 1 x 10(-7) M AVP-induced increases in cellular cAMP production were significantly enhanced by the Cl- removal. Also, 1 x 10(-7) M AVP-mobilized [Ca2+]i was augmented by the Cl- removal (181.3 vs. 224.5 nM, P < 0.05). The second study was carried out with the Krebs-Ringer buffered saline (KRB). Removal of Cl- lowered pHi from 7.20 to 7.09. AVP-induced increases in cellular cAMP production were significantly reduced in the Cl(-)-free KRB compared to those in the KRB. The reduction was obtained with KRB containing less than 25 mM Cl-. Similar results were obtained with 2 x 10(-8) M forskolin, a diterpene activator of adenylate cyclase. 1 x 10(-7) M AVP-mobilized [Ca2+]i was also diminished by the Cl(-)-free KRB. These results indicate that Cl- depletion affects the cellular response to AVP mediated via the changes in pHi in renal papillary collecting tubule cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Nucleotide sequences recognized by the AGAMOUS MADS domain of Arabidopsis thaliana in vitro.

The AGAMOUS gene of Arabidopsis thaliana is a homeotic gene involved in the development of stamens and carpels. This gene encodes a putative DNA-binding protein sharing a homologous region with the DNA-binding domains, MADS boxes, of yeast MCM1 and mammalian SRF. To examine the DNA-binding activity of the AGAMOUS protein, double-stranded oligonucleotides with random sequences of 40 bp in the central region were synthesized and mixed with the AGAMOUS MADS domain overproduced in Escherichia coli. Oligonucleotides which bound to the MADS domain were recovered by repeated immunoprecipitation with an antibody which recognizes the overproduced protein. From a comparison of the recovered DNA sequences, the consensus sequence of the high-affinity binding-sites for the AGAMOUS MADS domain was determined to be 5'-TT(A/T/G) CC(A/T)6GG(A/T/C)AA-3'. DNase I footprinting and methylation interference experiments showed that the MADS domain binds to this motif. Comparisons with the binding-site sequences of other MADS-box proteins revealed that the MCM1 binding-sites in a-mating type-specific promoters of Saccharomyces cerevisiae show similarities with the binding-site sequence of the AGAMOUS MADS domain. A synthetic MCM1 binding-site in the upstream region of the STE2 gene is recognized by the AGAMOUS MADS domain.

Arabidopsis↗