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Biomedical subjects

K Oda

Publications and source records attributed to K Oda.

At least 217 records · Page 12Linked to original sources
PubMed1997

Bioavailability of ruminally protected sulfamethoxazole after oral administration in ruminating calves.

Bioavailabilities of oral rumen-protected and non-protected formulations of sulfamethoxazole (SMS) were compared in ruminating calves, since in vitro degradation of SMX in ruminal fluid was confirmed. The coated with a gastric-acid-soluble polymer and uncoated formulations were administered to 3 calves through a catheter. Neither formulation could produce sufficient blood concentration of the drug, though the bioavailability of SMX for the coated formulation was higher than that for the uncoated formulation. It was suggested that the rumen-protected drug could improve the bioavailability by escaping from degradation in the rumen, but scarcely attain the effective levels in blood.

Administration, Oral↗
PubMed1997

Toxicity of a low level of indium phosphide (InP) in rats after intratracheal instillation.

To clarify the instillation toxicity of low level of indium phosphide (InP), 0, 1.2, 6.0 and 62.0 micrograms/kg body weight of InP particles were instilled intratracheally in male Fischer 344 rats, and the effects of InP were examined on the following day (day 1) and on the 8th day (day 8) after instillation. Indium was measured but not detected in the serum, liver, kidney, spleen, thymus and brain. Dose-related mild elevation of superoxide dismutase (SOD) activity and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluid (BALF) were found on day 1 without increases of inflammatory cells and total protein (TP) in BALF, which suggested the response of neutrophils and alveolar macrophages to instilled InP, and/or the manifestation of a very early stage of inflammation. Only in the 62.0 micrograms/kg-instilled group on day 8, were neutrophils, lymphocytes, TP, LDH, total phospholipid and total cholesterol in BALF increased, and desquamation of alveolar epithelial cells and amorphous exudate in alveolar lumen observed by histopathological examination. These results suggested that InP caused pulmonary inflammation and epithelial cell damage up to 8 days following instillation dose of 62.0 micrograms/kg, but that its effect was considered irrelevant at instillation doses of 6.0 micrograms/kg or below in rat.

Animals↗
PubMed1997

Reappraisal of the relationship between immunoglobulin heavy chain gene rearrangement and Epstein-Barr virus infection in Reed-Sternberg cells of Hodgkin's disease.

We investigated 44 cases of Hodgkin's disease for Epstein-Barr virus genome with EBER-1 in situ hybridization. Twenty of 44 (45.5%) were positive for EBV. Simultaneously, immunoglobulin gene rearrangements were assessed in 32 of these 44 cases with PCR on DNA extracted from Reed-Sternberg cell (RS-cell) -rich areas microdissected from paraffin sections. Clonally rearranged immunoglobulin (IgH) gene was observed in 15 cases (46.9%). EBV-negative cases showed more frequent IgH rearrangement than EBV-positive cases (10 and 5 cases, respectively). In 9 cases, the RS cells were CD20-positive immunohistochemically and these were all EBV negative and the IgH gene was rearranged in all except one. These findings may suggest that EBV infection has occurred before the immunoglobulin gene rearrangement or that EBV infection has influenced the rearrangement of the immunoglobulin gene. The results may also hint towards the obscure B-cell nature of the RS cells.

Adolescent↗
PubMed1997

Genotypes of Japanese encephalitis virus isolated in three states in Malaysia.

Two hundred forty nucleotides from the pre-membrane gene region of 12 Japanese encephalitis virus (JEV) strains isolated from three different regions of Malaysia from 1993 to 1994 were sequenced and compared with each other and with the JEV strains from different geographic areas in Asia. These 12 Malaysian isolates were classified into two genotypes. The four JEV strains isolated from Sarawak in 1994 and the four JEV strains isolated from Sepang, Selangor in 1993 were classified into one genotype that included earlier isolated strains from Malaysia (JE-827 from Sarawak in 1968 and WTP/70/22 from Kuala Lumpur in 1970). The four JEV strains from Ipoh, Perak in 1994 were classified into another genotype that included JEV strains isolated from northern Thailand and Cambodia. In an earlier report, 10 JEV strains from Sabak Bernam, Selangor in 1992 were classified into the largest genotype that included strains isolated in temperate regions such as Japan, China, and Taiwan. The data indicate that at least three genotypes of JEV have been circulating in Malaysia.

Amino Acid Sequence↗
PubMed1997

Changes in motor nerve terminals following proximal constriction by a ligature.

To elucidate the effect of proximal constriction on motor nerve terminals, silk ligations were placed around the tibial nerve in the thigh of rabbits. The ligatures were tight enough to cause Wallerian degeneration in most of the large myelinated fibers; we studied those which remained unaffected. A week after operation, 9 animals showed a fall in amplitude of medial plantar muscle action potential to less than 30% of the pre-operative value on tibial nerve stimulation at the ankle. They were killed after keeping the constriction from 10 to 100 days, and the medial plantar muscles were removed for histological studies on the motor terminals of the medial plantar nerve. AChE-silver staining showed many nerve endings without terminal axons, and "junctional" terminals showing preservation of the continuity proximal to complete degeneration from 10 days to the 40 days after ligation. A few terminal and nodal sproutings were found 10 days after ligation. Transverse sections of the intramuscular portion of the medial plantar nerve showed a decrease in number of the large myelinated fibers. While the ratio of axonal caliber/external diameter of large myelinated fibers (g-ratio) was reduced, g-ratio of small myelinated fibers were varied but as high as that in normal controls from 40 days after ligation. These results indicate distal axonal degeneration (dying back) of the terminal fibers besides the Wallerian degeneration at the level of the ligature and inhibited distal sproutings, which are probably caused by a local disturbance of axonal transport resulting from proximal constriction.

Action Potentials↗
PubMed1997

[MR dynamic subtraction angiography (MRDSA)].

We have developed magnetic resonance dynamic subtraction angiography (MRDSA), which depicts the long segments of arteries from the upper abdomen to the lower leg by using a small dose of Gd-DTPA. The lower half of the body was divided into three imaging regions, abdomen, thigh and lower leg, in the order of scanning. The contrast-enhanced three-dimensional breath-hold fast field echo technique with half Fourier acquisition was performed in 3 normal volunteers and 12 patients with vascular diseases (4: abdominal aortic aneurysm, 8: atherosclerotic occlusive disease). The images were reconstructed into composite images by using maximum-intensity-projection postprocessing after the subtraction of precontrast images. A bolus intravenous injection of a small dose of Gd-DTPA (0.02-0.05 mmol/kg) was given, followed by the five sets of scans. The acquisition time of each set was 8 to 16 seconds, and the total dose used in MRDSA was 0.1 to 0.15 mmol/kg. The image quality of MRDSA was satisfactory in 3 normal volunteers and 12 patients with vascular diseases. MRDSA demonstrated aortic aneurysm and atherosclerotic obstruction as clearly as conventional angiography. MRDSA can replace conventional angiography.

Angiography, Digital Subtraction↗
PubMed1997

Regulation of IL-2 signaling.

Several tyrosine kinases such as Jak1, Jak3, Lck and Syk are known to participate in IL-2-mediated intracellular signal transduction. Jak1, Lck and Syk are associated with the cytoplasmic domain of the beta chain, whereas Jak3 is associated with the cytoplasmic domain of the gamma chain, which is shared among receptors for IL-2, IL-4, IL-7 and IL-15. We first demonstrated that Jak1 is associated with the alpha chains of receptors for IL-4, IL-7 and IL-15 as well as the IL-2 receptor beta chain. Furthermore, we revealed that two proline residues in the box1 region, which is conserved in the IL-2 receptor beta chain and the alpha chains of the cytokine receptors, are essentially involved in association with Jak1. The MOLT4 transfectants with the box1 mutants of the IL-2 receptor beta chain lacking Jak1 association showed IL-2 responsiveness, in terms of activations of Jak3 and Stat5 and induction of cell growth, indicating that Jak1 is dispensable for IL-2-mediated cell growth signaling, and that Jak1 activation is not required for activation of Jak3 and Stat5 in the MOLT4 transfectants.

Amino Acid Sequence↗
PubMed1997

[Effects of pre-operative administration of steroids on the serum interleukin (IL)-6, IL-8 and organ injuries in replacement of thoracic aorta].

To investigate whether pre-operative steroids administration decreases the post-operative serum IL-6, IL-8 and prevents organ injuries, we prospectively studied patients undergoing elective replacement of thoracic aorta using an extracorporeal circulation. Six of 10 patients (group S) were pretreated with methylprednisolone 500 mg 2 hours before operation while the other 4 patients (group C) were not. Though post-operative serum IL-6, IL-8, C-reactive protein and amylase elevated in group C, the elevations were significantly decreased in group S (p < 0.05). These findings show that in replacement of thoracic aorta, pre-operative steroid administration decreases the post-operative elevations of serum inflammatory cytokines (IL-6 and IL-8) and may prevent organ injuries.

Aged↗
PubMed1997

Rapid diagnostic imaging of cancer using radiolabeled liposomes.

A novel tumor diagnostic imaging method was developed that allows tumor localization soon after administration of radiolabeled liposomes. Although previous studies showed that radiolabeled liposomes can reach various tumors in a short time, their blood clearance is slow, and the high blood background hinders early imaging. Therefore, we attempted to remove actively the liposomes from the circulation using the strong affinity between avidin and biotin. Liposomes that had biotin bound to their surface and were labeled with 111In, 67Ga, or 99mTc were administered to mice bearing sarcoma 180, followed by administration of avidin 2 or 4 h later. Avidin initiated liposomal aggregation, resulting in their rapid removal by the reticuloendothelial system. Consequently, their blood level was markedly reduced without any changes in tumor levels. The tumor-to-blood ratio reached about 13 at only 2.5 h after administration of 99mTc-labeled liposomes, versus 1.0 or less without postadministration of avidin. Increased liver accumulation was also observed, but it decreased gradually with time.

Animals↗
PubMed1997

Comparison of sequences of E/NS1 gene junction of dengue type 3 virus following culture subpassage in C6/36 cells to study the possible occurrence of mutations.

The aim of this study was to determine whether mutations could occur in the dengue virus genome following three subpassages of the virus in a mosquito cell line. This was done because sources of virus isolates used for sequencing studies are usually maintained in cell lines rather than in patients' sera. Therefore it must be assured that no mutation occurred during the passaging. For this purpose, sequencing was carried out using the polymerase chain reaction (PCR) products of the envelope/non-structural protein 1 junction region (280 nucleotides) of dengue type 3 virus. Sequence data were compared between the virus from a patient's serum against the virus subpassaged three times in the C6/36 cell line. We found that the sequence data of the virus from serum was identical to the virus that was subpassaged three times in C6/36 cell line.

Aedes↗
PubMed1997

[Clinical study on azithromycin in 10% fine granules and 100mg capsules in the field of pediatrics].

Azithromycin (AZM), a new oral macrolide antibiotic, in 10% fine granules or 100 mg capsules was given to pediatric patients to treat various infections. The following results were obtained in our studies of AZM for its antibacterial activities against clinical isolates, its pharmacokinetics, its efficacy, and its safety. 1. MICs of AZM, erythromycin (EM) and clarithromycin (CAM) were determined against a total of 57 strains all at 10(6) cfu/ml. Among Gram-positive cocci, MICs of AZM ranged from 0.78 to > 100 micrograms/ml against Staphylococcus aureus (20 strains), from 0.05 to 0.1 microgram/ml against Streptococcus pyogenes (11 strains), and from 0.0125 to 3.13 micrograms/ml against Streptococcus pneumoniae (10 strains). These MICs were similar to those of the other macrolides. Among Gram-negative bacilli, MICs of AZM were 0.05 micrograms/ml against Moraxella subgenus Branhamella catarrhalis (1 strain), from 0.78 to 3.13 micrograms/ml against Haemophilus influenzae (9 strains), 0.78 micrograms/ml against Haemophilus parainfluenzae (1 strain) and 6.25 micrograms/ml against salmonella sp. (1 strain). These values were similar to or lower than those of the other macrolides. Against Mycoplasma pneumoniae, MICs of AZM were < or = 0.0008 micrograms/ml in three strains. One strain of M. pneumoniae showed tolerance to AZM at MIC 25 micrograms/ml. The other agents exhibited higher MIC than AZM against this organism. 2. Plasma samples were collected from five patients receiving fine granules and four patients receiving capsules for drug level determination. The patients received AZM at 10.0 approximately 16.3 mg/kg body weight once daily for 3 days. Drug concentrations in plasma at two hours after Day 3 dosing were in a range between 0.02 and 0.19 micrograms/ml for fine granules and were in a range between 0.11 and 0.42 micrograms/ml for capsules. 3. Urine samples were collected from four patients receiving fine granules and four patients receiving capsules. Drug levels were determined to be 3 micrograms/ml at post-treatment 48 hours for fine granules and post-treatment 72 hours for capsules. Urinary excretion rates of AZM in three patients on capsules lied in a range between 4.69 and 10.17%. 4. Effectiveness of AZM in fine granules was evaluated in 128 patients having a total of 19 different infections. AZM was rated "excellent" in 51 patients, "good" in 63, "fair" in 8, "poor" in 6, resulting in an efficacy rate of 89.1%. Effectiveness of AZM in capsular form was evaluated in 23 patients with five different infections. AZM was found "excellent" in 13 patients and "good" in 10, resulting in an efficacy rate of 100%. 5. AZM in fine granules eradicated 45 strains of 54 in 8 different bacteria. AZM in capsules eradicated 9 strains of 10 strains in 6 different bacteria. 6. As for adverse reactions, one patient complained of eruption, one vomiting, one loose stool, five diarrhea, when administered with fine granular form of AZM. One patient on AZM capsules experienced urticaria and vomiting. 7. As for abnormal laboratory changes, three patients were found with decreased WBC, seven with increased eosinophil, two with increased GOT and GPT, one with increased GPT. They were all on fine granular form of AZM. As far as abnormalities found in patients administered with AZM in capsular form, two showed decreased WBC, one decreased WBC along with increased eosinophil, and three increased eosinophil.

Adolescent↗
PubMed1996

Overexpression of cysteine sulfinic acid decarboxylase stimulated by hepatocarcinogenesis results in autoantibody production in rats.

We developed a novel and efficient cDNA subtraction method to isolate rat hepatocellular carcinoma (HCC)-related genes. cDNAs from Solt-Farber procedure-driven HCCs were synthesized on Latex beads. The subtraction was accomplished by a simple centrifugation, PCR amplification, and dot blot screening. Among 2000 clones from the subtracted cDNA library, one clone with a full-length HCC-related cDNA was eventually obtained. Sequence analysis of this clone showed it to exhibit 90 and 60% similarity with the rat cysteine sulfinic acid decarboxylase (CSAD) and mammalian glutamic acid decarboxylases (GAD), respectively. Differences between our sequence data on CSAD and those reported previously were observed at two positions, which arose from a single amino acid substitution and frame shift mutation. The CSAD expression was restricted to the liver and kidney of rats. During hepatocarcinogenesis, expression of the CSAD mRNA and its protein was stimulated in the precancerous liver and maintained its high expression afterward. Interestingly, a high level of anti-CSAD autoantibody was detected in the HCC-bearing rats. The titer of anti-CSAD autoantibodies in these rats was 30-200 times higher than that in normal rats. The anti-CSAD autoantibody appeared in the precancerous state and was maintained afterward, and its pattern of appearance was similar to that of CSAD mRNAs and proteins. Thus, we propose that the high-titer CSAD autoantibody resulted from increased CSAD gene expression in the liver due to stimulation by the HCC. These results remind us of human autoimmune diseases including insulin-dependent diabetes mellitus and stiff-man syndrome, which are caused by autoantibodies against GAD.

Amino Acid Sequence↗
PubMed1996

Kinetic characterization of the neutral protease vimelysin from Vibrio sp. T1800.

The kinetics of the hydrolysis of dipeptide and tripeptide substrates by the recently discovered neutral protease from Vibrio species T1800 (vimelysin) were studied. In the pH dependence of the apparent second-order rate constant, the pKa2 value of vimelysin (approximately 6.5) was significantly lower than thermolysin (8.3), although the pKa1 (approximately 5.1) values were comparable (5.0). The Kcat/Km(lim) parameter for hydrolysis of Fua-Gly-PheNH2 (Fua = furylacryloyl) was more than sevenfold greater than for Fua-Gly-LeuNH2. This higher specificity for Fua-Gly-PheNH2 was deduced for both Kcat and Km parameters. Fua-Phe-PheNH2 showed the highest Kcat/Km(app) value of the six substrates studied. The discrimination between Phe/Leu at the P1' site was most evident when the P1 site was not sufficiently filled. Reflecting the characteristically high proteolytic activity of vimelysin at lower temperatures [Oda, K., Okayama, K., Okutomi, K., Shimada, M., Sato, R. & Takahashi, S. (1996) Biosci. Biotech. Biochem. 60, 463-467], the Arrhenius plot of the apparent second-order rate constant for the hydrolysis of Fua-Gly-LeuNH2 showed an inverse temperature dependence; higher reaction rates were observed at lower temperatures. This was not merely due to the pKa shift nor to thermal denaturation of the enzyme coupling, but rather to the Kcat(app) parameter, which alone showed an inverse temperature dependence. A model containing two temperature-dependent forms of the active enzyme was postulated to explain this unique temperature dependence.

Circular Dichroism↗
PubMed1996

Degradation of topoisomerase IIalpha during adenovirus E1A-induced apoptosis is mediated by the activation of the ubiquitin proteolysis system.

The human epithermoid carcinoma-derived cell line MA1, established by introduction of the adenovirus E1A 12 S cDNA linked to the mouse mammary tumor virus long terminal repeat, elicits apoptosis after induction of E1A12S in response to dexamethasone. The level of topoisomerase IIalpha begins to decrease steeply within 36 h preceding the onset of DNA fragmentation, whereas its mRNA level is unchanged (Nakajima, T., Ohi, N., Arai, T., Nozaki, N., Kikuchi, A., and Oda, K. (1995) Oncogene 10, 651-662). Topoisomerase IIalpha prepared by immunoprecipitation or extraction of the nuclear matrix was degraded much more efficiently in the S10 extract prepared from MA1 cells treated with dexamethasone for 42 h (the 42-h extract) than in the extract from untreated MA1 cells (the 0-h extract) in an ATP- and ubiquitin-dependent manner. The proteolytic activity for degradation of topoisomerase IIalpha was suppressed specifically by inhibitors for the proteasome and was much reduced in the 42-h extract prepared from MA1-derivative cell lines expressing E1B19k or Bcl-2. The proteolytic activity was lost after fractionation of the 42-h S10 extract into the S70 and P70 fractions by centrifugation at 70,000 x g for 6 h but partially recovered when these fractions were combined. Polyubiquitinated forms of topoisomerase IIalpha could be detected by incubating it in the S70 or S100 extract, which lacks most of the proteasome activity. The ubiquitination activity in S70 prepared from the 42-h extract was 4- to 5-fold higher than that prepared from the 0-h extract. These results suggest that a component(s) in the ubiquitin proteolysis pathway, responsible for ubiquitination and degradation of topoisomerase IIalpha, is activated or induced during the latent phase of E1A-induced apoptosis.

Adenosine Triphosphate↗
PubMed1996

Bip/GRP78 but not calnexin associates with a precursor of glycosylphosphatidylinositol-anchored protein.

When fused in-frame with a C-terminal propeptide of placental alkaline phosphatase (PLAP), rat alpha 2u-globulin (alpha GL), a nonglycosylated secretory protein, was expressed on the cell surface as a glycosylphosphatidylinositol (GPI)-linked chimaeric protein (alpha GL-PLAP). In contrast with the wild-type alpha GL-PLAP, a mutant, in which Asp at the cleavage/attachment site of GPI was replaced by Trp, failed to become a GPI-linked mature form and was retained as a precursor form within the cell [Oda, Cheng, Saku, Takami, Sohda, Misumi, Ikehara and Millán (1994) Biochem. J. 301, 577-583]. To elucidate the molecular interactions involved in the retention of the proform within the cell, we examined the association of the proform with molecular chaperones in the endoplasmic reticulum (ER). Antibody against the ER retrieval motif KDEL coimmunoprecipitated a 25 kDa proform, but not a 22 kDa GPI-linked mature form. Pulse-chase experiments showed that the wild-type alpha GL-PLAP with a cleavable propeptide was converted into the mature form, whereas the mutant alpha GL-PLAP with an uncleavable propeptide remained associated with ER-resident proteins with a KDEL motif and underwent rapid degradation in a pre-Golgi compartment. Chemical cross-linking studies showed that, of the several ER-resident proteins immunoreactive with the anti-KDEL antibody, a 78 kDa protein was the only protein associated with the proform. Furthermore this 78 kDa protein was dissociated from the precursor molecule on incubation with ATP, allowing us tentatively to assign it as Bip/GRP78. Anticalnexin antibody, however, failed to coprecipitate any form of the chimaeric protein. Immunoelectron microscopy showed that the proform with the uncleavable propeptide was localized in the ER, but not detected in the Golgi apparatus or plasma membranes. Taken together, these results suggest that Bip/GRP78 is associated with pro alpha GL-PLAP and retains it within the ER until pro alpha GL-PLAP is either modified by GPI or degraded, thereby participating in the quality control of this GPI-linked chimaeric protein.

Adenosine Triphosphate↗
PubMed1996

Lack of endothelin ETB receptor binding and function in the rat with a mutant ETB receptor gene.

Congenital aganglionosis rat is a mutant with an autosomal recessive gene (sl). Recent studies have revealed that the endothelin ETB receptor gene of sl/sl rat has a deletion of 301-bp region spanning exon 1 and intron 1 corresponding to the first and the second transmembrane domains of the receptor. In the present experiments, we examined the functions of ETB receptors in the sl/sl rats. In the membranes of cerebellum, heart, and lung of control (+/+ and sl/+) rats, ET-1 induced a monophasic, competitive displacement of [125I]ET-1 binding, whereas ET-3, IRL 1620, and BQ-123 showed biphasic displacement. In the membranes of sl/sl rats, in contrast, ET-1, BQ-123, ET-3, and IRL 1620 showed only monophasic displacement. Scatchard analysis revealed a single [125I]ET-3 binding site in the membrane of control heart but not in the sl/sl rat heart, and the specific binding sites for [125I]ET-1 in both control and sl/sl rat hearts. In the control rat aorta but not in the sl/sl rat aorta, ET-3 induced endothelium-dependent relaxation. These results suggest that sl/sl rats do not have functional ETB receptors.

Animals↗
PubMed1996

Lactacystin, an inhibitor of the proteasome, blocks the degradation of a mutant precursor of glycosylphosphatidylinositol-linked protein in a pre-Golgi compartment.

When transiently expressed in the COS-1 cell, a mutant chimeric protein with an uncleavable glycosylphosphatidylinositol (GPI) -anchor signal failed to be modified by GPI and undergoes rapid degradation in a pre-Golgi compartment. Among several protease inhibitors, 3,4-dichloroisocoumarin and N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal, potent inhibitors of the proteasome, strongly inhibited the degradation of the mutant protein. Furthermore, lactacystin, a highly specific inhibitor of the proteasome, was found to block the degradation. These results suggest that the pre-Golgi degradation pathway is functionally linked to the proteolytic system dependent on the proteasome, which hitherto was believed to play a role mostly in the cytoplasm and nucleus.

Acetylcysteine↗