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Biomedical subjects

K Oda

Publications and source records attributed to K Oda.

At least 73 records · Page 4Linked to original sources
PubMed2000

Effect of a novel bifunctional endothelin receptor antagonist, IRL 3630A, on guinea pig respiratory mechanics.

This study characterized the in vitro pharmacological properties of a newly developed endothelin receptor antagonist, N-butanesulfonyl-[N-(3, 5-dimethylbenzoyl)-N-methyl-3-[4-(5-isoxazolyl)-phenyl]-(D)- alanyl]-( L)-valineamide sodium salt (IRL 3630A), and its in vivo effects on respiratory mechanics were determined. IRL 3630A showed highly balanced affinities to human endothelin ET(A) and ET(B) receptors, giving apparent K(i) values of 1.5 and 1.2 nM, respectively. This compound also potently antagonized the endothelin-1-induced intracellular Ca(2+) increases in both embryonic bovine tracheal (EBTr) cells expressing endothelin ET(A) receptors and human Girardi heart (hGH) cells expressing endothelin ET(B) receptors. In guinea pig isolated tracheas having both endothelin ET(A) and ET(B) receptors, IRL 3630A greatly inhibited endothelin-1-induced contraction (pA(2)=7.1), which was partially or scarcely suppressed by the endothelin ET(A) receptor antagonist cyclo[-(D)-Trp-(D)-Asp-(L)-Pro-(D)-Val-(L)-Leu-] (BQ-123) or the endothelin ET(B) receptor antagonist N-(3, 5-dimethylbenzoyl)-N-methyl-3-(4-phenyl)-(D)-phenylalanyl-(L)-t ryptop han (IRL 2500), respectively. Bolus i.v. injections of IRL 3630A administered into anaesthetized guinea pigs at 10 and 30 microg/kg inhibited endothelin-1 (1.3 microg/kg)-induced changes in respiratory resistance and compliance in a dose dependent manner, whereas both sodium 2-benzo[1, 3]dioxol-5-yl-4-(4-methoxy-phenyl)-4-oxo-3-(3,4, 5-trimethoxy-benzyl)-but-2-enoate (an endothelin ET(A) receptor antagonist: PD 156707) and IRL 2500 at doses of up to 30 microg/kg did not affect endothelin-1-induced changes in respiratory mechanics, reflecting the in vitro results. IRL 3630A is thus an effective bifunctional endothelin receptor antagonist, and will be useful in clarifying the role of endothelin in pulmonary diseases such as bronchial asthma.

Airway Resistance↗
PubMed2000

p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53.

Through direct cloning of p53 binding sequences from human genomic DNA, we have isolated a novel gene, designated p53AIP1 (p53-regulated Apoptosis-Inducing Protein 1), whose expression is inducible by wild-type p53. Ectopically expressed p53AIP1, which is localized within mitochondria, leads to apoptotic cell death through dissipation of mitochondrial A(psi)m. We have found that upon severe DNA damage, Ser-46 on p53 is phosphorylated and apoptosis is induced. In addition, substitution of Ser-46 inhibits the ability of p53 to induce apoptosis and selectively blocks expression of p53AIP1. Our results suggest that p53AIP1 is likely to play an important role in mediating p53-dependent apoptosis, and phosphorylation of Ser-46 regulates the transcriptional activation of this apoptosis-inducing gene.

Adenocarcinoma↗
PubMed2000

A novel double-headed proteinaceous inhibitor for metalloproteinase and serine proteinase.

A novel proteinaceous inhibitor for the metalloproteinase of Streptomyces caespitosus has been isolated from the culture supernatant of Streptomyces sp. I-355. It was named ScNPI (Streptomyces caespitosus neutral proteinase inhibitor). ScNPI exhibited strong inhibitory activity toward ScNP with a K(i) value of 1.6 nm. In addition, ScNPI was capable of inhibiting subtilisin BPN' (K(i) = 1.4 nm) (EC ). The scnpi gene consists of two regions, a signal peptide (28 amino acid residues) and a mature region (113 amino acid residues, M(r) = 11,857). The deduced amino acid sequence of scnpi showed high similarity to those of Streptomyces subtilisin inhibitor (SSI) and its homologues. The reactive site of ScNPI for inhibition of subtilisin BPN' was identified to be Met(71)-Tyr(72) bond by specific cleavage. To identify the reactive site for ScNP, Tyr(33) and Tyr(72), which are not conserved among other SSI family inhibitors but are preferable amino acid residues for ScNP, were replaced separately by Ala. The Y33A mutant retained inhibitory activity toward subtilisin BPN' but did not show any inhibitory activity toward ScNP. Moreover, a dimer of ternary complexes among ScNPI, ScNP, and subtilisin BPN' was formed to give the 2:2:2 stoichiometry. These results strongly indicate that ScNPI is a double-headed inhibitor that has individual reactive sites for ScNP and subtilisin BPN'.

Amino Acid Sequence↗
PubMed2000

Influence of antigenic forms and adjuvants on protection against a lethal infection of Aujeszky's disease virus.

The influence of antigenic forms and adjuvant types on protection against a lethal infection of Aujeszky's disease virus (ADV) in mice was investigated. Antiviral IgG2a antibody response against particulate (inactivated ADV) and soluble antigen (ADV solubilized with deoxychorate-Na) in approximate order of extent was ISA70>QS-21>positively charged liposome>negatively charged liposome>weak negatively charged liposome>ISA25>lablabside F saponin>aluminum phosphate gel>non adjuvant. Particulate antigen induced higher IgG2a antibody production than soluble antigen. Particulate antigen combined with ISA70, ISA25 or positively charged liposome gave 100, 50 and 40% protection to mice, respectively. In contrast, soluble antigen plus ISA70 conferred 30% protection on mice. Immunogens using the other adjuvants gave </=20% protection to mice. These results indicate that a combination of particulate antigen and an appropriate adjuvant effectively induces the production of antiviral IgG2a antibody and provides protection against a lethal ADV infection in mice.

Adjuvants, Immunologic↗
PubMed2000

Inefficient function of the signal sequence of PTHrP for targeting into the secretory pathway.

Parathyroid hormone-related peptide (PTHrP) is not only secreted out of cells, but also targeted to the nucleoli due to a nucleolar targeting signal (NTS). We assessed the molecular mechanism underlying the dual targeting of PTHrP by constructing a series of truncated forms of rat PTHrP cDNA and expressing them in CHO cells. Immunostaining was observed in both the Golgi apparatus and nucleoli in the same cell expressing PTHrP with the N-terminal full-length signal sequence. When PTHrP molecules were translated from CUGs downstream of the AUG-initiator codon in the signal sequences, potential alternative initiators of the translation, they were exclusively localized in the nucleoli. In contrast, when a construct containing only the ATG-initiator codon was expressed, PTHrP was found to localize in both the nucleolus and the Golgi apparatus. No nucleolar staining of PTHrP was observed in the CHO cells transfected with PTH/PTHrP receptors even after incubating with a conditioned medium containing PTHrP, ruling out a possibility that PTHrP is, once secreted, internalized via receptor-mediated endocytosis and subsequently conveyed to nucleoli. Compatible with these morphological observations, a preproform of PTHrP was found in the cells expressing PTHrP in addition to proPTHrP, indicative of molecules along the secretory pathway. These results strongly indicate that the signal sequence of PTHrP is not sufficient to direct all the newly synthesized molecules across the endoplasmic reticulum, resulting in part of it being delivered to the nucleoli due to the NTS.

Amino Acid Sequence↗
PubMed2000

Possible interference between tissue-non-specific alkaline phosphatase with an Arg54-->Cys substitution and acounterpart with an Asp277-->Ala substitution found in a compound heterozygote associated with severe hypophosphatasia.

Tissue-non-specific alkaline phosphatase (TNSALP) with an Arg(54)-->Cys (R54C) or an Asp(277)-->Ala (D277A)substitution was found in a patient with hypophosphatasia [Henthorn,Raducha, Fedde, Lafferty and Whyte (1992) Proc. Natl. Acad. Sci. U.S.A.89, 9924-9928]. To examine effects of these missense mutations onproperties of TNSALP, the TNSALP mutants were expressed ectopically inCOS-1 cells. The wild-type TNSALP was synthesized as a 66-kDa endo-beta-N-acetylglucosaminidase H (Endo H)-sensitive form, and processed to an 80-kDa mature form, which is anchored to the plasma membrane via glycosylphosphatidylinositol (GPI). Although the mutant proteins were found to be modified by GPI, digestion with phosphatidylinositol-specific phospholipase C, cell-surface biotinylation and immunofluorescence observation demonstrated that the cell-surface appearance of TNSALP (R54C) and TNSALP (D277A) was either almost totally or partially retarded respectively. The 66-kDa Endo H-sensitive band was the only form, and was rapidly degraded in the cells expressing TNSALP (R54C). In contrast with cells expressing TNSALP(R54C), where alkaline phosphatase activity was negligible, significant enzyme activity was detected and, furthermore, the 80-kDa mature form appeared on the surface of the cells expressing TNSALP (D277A). Analysis by sedimentation on sucrose gradients showed that a considerable fraction of newly synthesized TNSALP (R54C) and TNSALP(D277A) formed large aggregates, indicating improper folding and incorrect oligomerization of the mutant enzymes. When co-expressed with TNSALP (R54C), the level of the 80-kDa mature form of TNSALP (D277A)was decreased dramatically, with a concomitant reduction in enzyme activity in the co-transfected cell. These findings suggest that TNSALP(R54C) interferes with folding and assembly of TNSALP (D277A) intrans when expressed in the same cell, thus probably explaining why a compound heterozygote for these mutant alleles developed severe hypophosphatasia.

Alanine↗
PubMed2000

In vivo imaging of adenovirus-mediated over-expression of dopamine D2 receptors in rat striatum by positron emission tomography.

PET was used to provide in vivo imaging of the over-expression of dopamine D2 receptor (D2R) induced by adenovirus vector-mediated gene transfer in rat striatum. The uptake of three kinds of D2R-specific ligands, [11C]raclopride, [11C]nemonapride and [11C]N-methylspiperone, measured by PET was higher in the striatum injected with the vectors for D2R than the contralateral striatum injected with a control vector 2-3 days after injection. However, the uptake of [11C]SCH 23390, a dopamine D1 receptor specific ligand, or [11C]beta-CIT-FP, a dopamine transporter specific tracer, was not different between bilateral striata. Co-injection of excess unlabeled raclopride inhibited the uptake of [11C]raclopride. At day 16 the increased uptake of [11C]raclopride declined to basal level, consistent with past in vitro assessment of this vector. In vivo imaging of D2R will permit longitudinal assessment of the efficiency of this and similar vectors in rat brain that can be related to functional changes being observed.

Adenoviridae↗
PubMed2000

Characterization of endopeptidase activity of tripeptidyl peptidase-I/CLN2 protein which is deficient in classical late infantile neuronal ceroid lipofuscinosis.

Endopeptidase activities of the CLN2 gene product (Cln2p)/tripeptidyl peptidase I (TPP-I), purified from rat spleen, were studied using the synthetic fluorogenic substrates. We designed and constructed decapeptides, based on the known sequence cleavage specificities of bacterial pepstatin-insensitive carboxyl proteases (BPICP). MOCAc-Gly-Lys-Pro-Ile-Pro-Phe-Phe-Arg-Leu-Lys(Dnp)r-NH(2) is readily hydrolyzed by Cln2p/TPP-I (K(cat)/K(m) = 7.8 s(-1) mM(-1)). The enzyme had a maximal activity at pH 3.0 for an endopeptidase substrate, but at pH 4.5 with respect to tripeptidyl peptidase activity. Both endopeptidase and tripeptidyl peptidase activities were strongly inhibited by Ala-Ala-Phe-CH(2)Cl, but not inhibited by tyrostatin, an inhibitor of bacterial pepstatin-insensitive carboxyl proteases, pepstatin, or inhibitors of serine proteases. Fibroblasts from classical late infantile neuronal ceroid lipofuscinosis patients have less than 5% of the normal tripeptidyl peptidase activity and pepstatin-insensitive endopeptidase activity. Cln2p/TPP-I is a unique enzyme with both tripeptidyl peptidase and endopeptidase activities for certain substrate specificity.

Amino Acid Sequence↗
PubMed2000

Intrasubject correlation between static scan and distribution volume images for [11C]flumazenil PET.

Accumulation of [11C]flumazenil (FMZ) reflects central nervous system benzodiazepine receptor (BZR). We searched for the optimal time for a static PET scan with FMZ as semi-quantitative imaging of BZR distribution. In 10 normal subjects, a dynamic series of decay-corrected PET scans was performed for 60 minutes, and the arterial blood was sampled during the scan to measure radioactivity and labeled metabolites. We generated 13 kinds of "static scan" images from the dynamic scan in each subject, and analyzed the pixel correlation for these images versus distribution volume (DV) images. We also analyzed the time for the [11C]FMZ in plasma and tissue to reach the equilibrium. The intra-subject pixel correlation demonstrated that the "static scan" images for the period centering around 30 minutes post-injection had the strongest linear correlation with the DV image. The ratio of radioactivity in the cortex to that in the plasma reached a peak at 40 minutes after injection. Considering the physical decay and patient burden, we conclude that the decay corrected static scan for [11C]FMZ PET as semi-quantitative imaging of BZR distribution is to be optimally acquired from 20 to 40 minutes after injection.

Adult↗
PubMed2000

DNA polymerases and Ki-67 nuclear antigen are induced in correlation with the resected mass of rat liver up to 90%.

BACKGROUND AND AIMS: We studied the regeneration potential by measuring induction of DNA polymerases in the remnant rat liver after a partial hepatectomy (PHx) that is maximal but compatible with survival. METHODS: The regenerating rat liver was obtained after the 90% PHx. The induction of activities of DNA polymerase alpha, delta, and epsilon were measured after partial purification. The Ki-67 nuclear antigen was also detected histochemically. These parameters were compared with those after both 30% and 70% PHx. RESULTS: The 90% hepatectomy resulted in the strong inductions of DNA polymerase alpha, delta, and epsilon, at 48 h after operation, in association with increases in wet weight and total DNA in the remnant liver. The enzyme induction was much higher after 90% PHx than after 30% and 70% hepatectomy, in correlation with the resection volume. At 48 h after 90% hepatectomy, the Ki-67 positive cells increased up to 47.2% of hepatocytes in the remnant liver. CONCLUSION: The higher induction of replication enzymes by 90% hepatectomy reflects more cells entering mitogenic cell cycle, which supports the fast regeneration of the remnant liver. The number of proliferating hepatocytes is stringently controlled by an unknown mechanism sensing the mass of resected liver parenchyma.

Animals↗
PubMed2000

Aggressive preoperative management and extended surgery for hilar cholangiocarcinoma: Nagoya experience.

From 1977 to 1997, surgical resection was possible in 142 (80%) of 177 patients with hilar cholangiocarcinoma after relieving jaundice by single or multiple percutaneous transhepatic biliary drainage followed by percutaneous transhepatic cholangioscopy and/or percutaneous trans-hepatic portal vein embolization. Curative resection was possible in 108 (61%) of the 142 patients, and 100 of these patients underwent various types of hepatectomy with caudate lobectomy for a 30-day operative mortality rate of 6% and 9% hospital mortality. Combined portal vein resection was carried out in 43 cases including 41 hepatectomies and 2 bile duct resections. Hepatopancreatoduodenectomy was performed in 16 patients. Cancer recurrence was observed in 58 of the 108 patients undergoing curative resection. The 3-, 5-, and 10-year survival rates for 100 patients undergoing curative hepatectomy and 8 with curative bile duct resection were 43%, 26%, and 19%; and 31%, 16%, and 0%, respectively; those for 40 patients with positive lymph node metastasis, 84 with perineural invasion, and 43 with combined portal vein resection were 27%, 14%, and 7%; 34%, 21%, and 13%; and 18%, 6%, and 0%, respectively. These survival rates are significantly better than those for 35 patients with unresectable cancer. Curative resection after aggressive preoperative management is recommended as a reasonable surgical approach to hilar cholangiocarcinoma.

Adult↗
PubMed2000

Comparison of visual function after foveal translocation with 360 degrees retinotomy and with scleral shortening in a patient with bilateral myopic neovascular maculopathy.

PURPOSE: To compare the visual outcome after foveal translocation by scleral shortening and that after 360 degrees retinotomy with extraocular muscle surgery in a patient with bilateral myopic neovascular maculopathy. METHODS: Case report. RESULTS: A 52-year-old woman with bilateral myopic neovascular maculopathy underwent foveal translocation with scleral shortening in the left eye, and visual acuity improved from 20/70 to 20/30. However, choroidal neovascularization recurred, and the final visual acuity was 20/40 after excision of the choroidal neovascularization. Foveal translocation with 360 degrees retinotomy was performed on the right eye, and visual acuity improved from 20/150 to 20/30. The critical print size was better, and the retinal sensitive area was larger in the right eye. CONCLUSION: The better reading ability shown by foveal translocation by a 360 degrees retinotomy compared with scleral shortening may stem from a larger retinal sensitive area obtained by this method.

Choroidal Neovascularization↗
PubMed2000

Studies on the genotype-phenotype relation in the hph-1 mouse mutant deficient in guanosine triphosphate (GTP) cyclohydrolase I activity.

The guanosine triphosphate (GTP) cyclohydrolase I (GTP-CHI) catalyses the rate-limiting step in the de novo synthesis of tetrahydrobiopterin, a cofactor of three aromatic amino acid hydroxylases, one of which is phenylalanine hydroxylase. The hph-1 mouse mutant deficient in GTP-CHI activity exhibits hyperphenylalaninemia which peculiarly disappears at 3 weeks of age, thus corresponding to the increase in liver GTP-CHI activity. The present gas chromatographic-mass spectrometric analysis of the phenylalanine and catecholamine metabolisms demonstrated the former metabolism to remain disturbed even in adult hph-1, which demonstrated a metabolic basis for sensitivity to the phenylalanine challenge in adult hph-1. A Northern blot analysis showed the hepatic GTP-CHI RNA expression in hph-1 at 2, 3 and 4 weeks of age to parallel the peculiar time course of the enzyme activity previously reported. No mutation was detected in either the coding region or the 5' flanking region (nt.-1 to -746) of the GTP-CHI gene of the hph-1. Further molecular genetic analyses are therefore required to elucidate the mechanism of the peculiar phenotype of hph-1.

Animals↗
PubMed2000

A PET study of adenosine A1 receptor in anesthetized monkey brain.

We demonstrated the distribution of adenosine A1 receptors in the anesthetized monkey brain with positron emission tomography (PET) using [(11)C]KF15372 ([1-propyl-(11)C]8-dicyclopropylmethyl-1, 3-dipropylxanthine). [(11)C]KF15372 was injected intravenously. The regional standardized uptake values and the distribution volume were calculated. We also investigated the effect of carrier on the uptake and regional brain distribution of [(11)C]KF15372. The use of [(11)C]KF15372 with dynamic PET scanning could be an appropriate method to analyze the regional binding potential of adenosine A1 receptors in living brain.

Anesthesia↗
PubMed2000

Preparation of a water-soluble fluorinated zinc phthalocyanine and its effect for photodynamic therapy.

An amphiphilic fluorinated phthalocyanine, zinc tetracarboxyoctafluorophthalocyanine (ZnC4F8Pc) was synthesized and characterized. Its photodynamic efficiency for HeLa cells was compared with hydrophilic zinc octacarboxyphthalocyanine (ZnC8Pc) and hydrophobic zinc hexadecafluorophthalocyanine (ZnF16Pc). ZnC4F8Pc had a remarkable photodynamic effect among the phthalocyanines used. The effect is apparently caused by the fact that ZnC4F8Pc is mainly accumulated in the hydrophobic lipid membrane and is in the photoactive monomer form in HeLa cells.

Fluorine↗
PubMed2000

Activity and stability of a neutral protease from Vibrio sp. (vimelysin) in a pressure-temperature gradient.

The apparent second-order rate constant of hydrolysis of Fua-Gly-LeuNH2 by vimelysin, a neutral protease from Vibrio sp. T1800, was measured in a variable pressure-temperature gradient (0. 1-400 MPa and 5-40 degrees C). The apparent maximum rate was observed at approximately 15 degrees C and 150-200 MPa; the pressure-activation ratio (kcat/Km(max)/kcat/Km(0.1 MPa)) was reached about sevenfold. The pressure dependence of the kcat and Km parameters at constant temperature (25 degrees C) revealed that the pressure-activation below 200 MPa was mainly caused by a change in the kcat parameter. The change in the intrinsic fluorescence intensity of vimelysin was also measured in a pressure-temperature plane (0.1-400 MPa and -20 to +60 degrees C). The fluorescence intensity was found to decrease by increasing pressure and temperature, and the isointensity contours were more or less circular. The tangential lines to the contours at high temperatures and low to medium pressures seem to have slightly positive slopes, which was reflected by the higher residual activities left after incubations at higher temperatures and medium pressure (200 MPa and 50 degrees C) and by the almost intact secondary structure left after 1 h of incubation at 200 MPa and 40 degrees C, as studied by circular dichroism. These results were compared with the corresponding results for thermolysin, a moderately thermostable protease from Bacillus thermoproteolyticus. Apparent differences that might be related to the temperature adaptations of the respective source microbes are also discussed.

Bacillus↗
PubMed2000

Sepsis in children.

BACKGROUND: Sepsis remains lethal to children. At our institution, we have noted that approximately 2% of all hospitalized patients have had sepsis. In the present study, we analyzed episodes of sepsis that occurred in our ward. METHODS: Sepsis that occurred in our institution between January 1984 and December 1998 was reviewed and analyzed. RESULTS: Three hundred and sixty-six episodes of sepsis in 244 admitted patients were analyzed. Sepsis occurred in approximately 2% of all hospitalized patients. Forty-three of 244 patients were under 1 year of age. Eighty-seven percent (212/244) of cases had underlying diseases. Hematologic disorders or neoplasms were the most common underlying disease, comprising 55% of all patients (133/244). Two-hundred and fifty-one of 366 episodes of sepsis were acquired during hospitalization. We identified 409 causative agents. There were 25 polymicrobial infections (25/366; 7%). Gram-positive bacteria comprised 68% of all organisms (280/409). Staphylococcus aureus was the most common organism, comprising 18% of causing agents (75/409). Sixty-six organisms came from the insertion of a central venous catheter. Eighty-one patients experienced recurrent episodes of sepsis. In terms of complications, respiratory distress was the most common complication (36 episodes) and there were 15 episodes of shock. Thirty-seven patients died of sepsis. Sepsis caused by Gram-negative bacteria showed significantly higher mortality than Gram-positive bacteria (11/43 (26%) vs 15/146 (10%); P= 0.053). CONCLUSIONS: In our institution, approximately 20% of septic patients were under 1 year of age and 90% had underlying diseases. The causative agents of sepsis affected the outcome.

Adolescent↗