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Biomedical subjects

T Oda

Publications and source records attributed to T Oda.

At least 469 records · Page 26Linked to original sources

Double cardia. An unusual sequela of reflux esophagitis with ulcer.

We report a patient with acquired "double cardia" (esophagogastric fistula). She was a 76-year-old farmer's widow with severe kyphosis. She presented with postprandial heartburn one month after the initiation of nifedipine and isosorbide dinitrate. Radiologic and endoscopic examinations revealed an esophagogastric fistula, short esophagus with hiatal hernia, Barrett's esophagus with reflux esophagitis, and ulcer. This case shows that repeated reflux esophagitis and esophageal ulcer, complicated with short esophagus and hiatal hernia, can predispose to the formation of esophagogastric fistula.

Aged↗

A site of action of dexamethasone on leukocyte extravasation in microcirculation.

When leukotriene (LT) B4 (15 pmol/50 microliters) was applied topically over the microvasculature of the hamster cheek pouch, polymorphonuclear (PMN) leukocytes started rolling and adhering on the inner wall of the venule. Over 90% of the PMN leukocytes adhered disappeared from the vascular lumen, taking 7.3 +/- 0.6 min for disappearance. Then, the PMN leukocytes stayed in the space between the endothelial cells and the pericyte basement membrane, as ascertained by electron micrographs. The number, which could be counted in the space, increased to 2.7, 12.2 and 19.2 cells on the TV screen for 30, 60 and 90 min, respectively. Administration of dexamethasone (0.1 or 0.3 mg/kg, i.p.) two hours before the LTB4 application did not cause the reduction of the numbers of adhered leukocytes nor the rate of disappearance, but reduced the numbers of leukocytes present in the interstitial space. Thus, dexamethasone inhibited the step of the penetration of the pericyte basement membrane.

Animals↗

Reduced bone marrow toxicity of neocarzinostatin by conjugation with divinyl ether-maleic acid copolymer.

Neocarzinostatin (NCS) was conjugated with divinyl ether-maleic acid anhydride copolymer (pyran copolymer), and its therapeutic effect was compared with that of NCS. The conjugated NCS (pyran-NCS) with a molecular weight of about 23,000, exhibited in vitro cytotoxic activity against eight cell lines and bone marrow cells that was similar to the cytotoxic activity of NCS on a molar basis. Furthermore, both drugs had similar effects against a multidrug-resistant Chinese hamster ovary cell line (CHR C5) and its parent cell line (AUXB1) in vitro. However, pharmacological analysis showed that pyran-NCS had reduced accumulation in the spleen, and most important was three times less hematotoxic in vivo compared with NCS. Also, pyran-NCS had a 1.7-fold higher 50% lethal dose (LD50). Antitumor activity of pyran-NCS and NCS was tested against two different forms of Meth A tumor. In a solid tumor model, pyran-NCS and NCS suppressed tumor growth at three-fourths of the LD50 to 12.8 and 19.0% of the control tumor as evaluated on day 28, respectively (P less than 0.025). In an ascitic tumor model, the percentage increase in the median life span caused by pyran-NCS and NCS was more than 400 and 150% on day 60, respectively. Pyran-NCS is more effective than NCS because the reduced acute toxicity permits an increased drug dosage.

Animals↗

Free radical generation during brief period of cerebral ischemia may trigger delayed neuronal death.

We investigated the pathogenic role of free radical formation in ischemic neuronal death using radical scavenger, superoxide dismutase. Cerebral ischemia was produced in the gerbil by bilateral common carotid occlusion for 5 min, which consistently resulted in delayed neuronal death in the CA1 region of the hippocampus. The effects of free superoxide dismutase and a derivatized superoxide dismutase, pyran copolymer conjugated superoxide dismutase, on early ischemic damages, detected sensitively by the immunohistochemical reaction for microtubule associated protein 2, and a subsequent delayed neuronal death after restoration of blood flow were investigated. Preischemic treatment by pyran conjugated superoxide dismutase showed clear protective effects against both the neuronal damages detected by immunohistochemistry after 5 min ischemia and the delayed neuronal necrosis after one week of recovery, although no clear beneficial effects were observed when this drug was administered just before the recirculation or free superoxide dismutase was used. These results strongly suggest that free radical generation during brief period of ischemia plays a pivotal role in triggering the ischemic neuronal damages causing delayed neuronal death at the selectively vulnerable areas of the brain.

Animals↗

Enhanced intestinal absorption of a hydrophobic polymer-conjugated protein drug, smancs, in an oily formulation.

Intestinal absorption of neocarzinostatin (NCS) and smancs (copolystyrene maleic acid-conjugated NCS), in aqueous and oily formulations, was investigated after oral administration in mice. Blood concentrations of NCS and smancs were determined with a cytotoxicity assay employing the highly sensitive Epstein-Barr (EB) virus-transformed B-lymphoblastoid cell line, TK/B. Smancs was more efficiently absorbed from a medium-chain triglyceride solution (oily smancs) than from an aqueous solution in phosphate-buffered saline (PBS). The maximum blood concentration and the area under the concentration curve versus time course (AUC) of oily smancs were 9 and 11 times greater than those of the aqueous form of smancs, respectively. At 5 hr after administration of oily smancs, 0.044% of the total smancs dose was found in blood, whereas the parent compound NCS was not detectable at any time. When oily smancs was administered orally to sarcoma 180 tumor-bearing mice, a selective accumulation of smancs in tumor tissue was observed. These results indicated that a biologically active protein, which cannot be used orally, may be rendered orally active drug by conjugation with a hydrophobic polymer in combination with an oily formulation.

Administration, Oral↗

Purification of two transcription factors required for initiation by mammalian RNA polymerase II.

We have purified two general transcription factors (FA and FE) necessary for specific transcription by mammalian RNA polymerase II to near homogeneity. Both activities are associated with peptides of approximately 33 kDa. FA and FE do not replace one another and show different kinetics of action in a sarkosyl block assay. In particular, FE participated in a rapid reaction after the formation of an initial complex with the other transcription factors. Furthermore, FE can associate with purified calf thymus RNA polymerase II.

Animals↗

Effects of gonadotropin-releasing hormone agonists on meiotic maturation of follicle-enclosed oocytes in rabbits.

The effects of GnRH agonists on in vitro maturation of rabbit follicle-enclosed oocytes were studied. Rabbit preovulatory follicles were cultured with or without hCG (10(2) ng/ml), buserelin (10(2)-10(5) ng/ml), or leuprolide (10(2)-10(5) ng/ml) for 14 hours in vitro. GnRH agonists induced the resumption of meiosis in the follicle-enclosed oocytes in a dose-dependent manner. The percentage of oocytes achieving GVBD following treatment with 10(5) ng/ml buserelin (87.9 +/- 6.3%) or 10(5) ng/ml leuprolide (86.0 +/- 4.1%) did not differ significantly from hCG-treated control (87.3 +/- 3.8%). Mature oocytes initially were detected within 2 hours of GnRH agonist exposure. Concomitant addition of a GnRH antagonist at 10(4) ng/ml significantly blocked the stimulatory effect of GnRH agonist on oocyte maturation. GnRH agonists significantly stimulated both prostaglandin (PG) E2 (PGE2) and PGF2 alpha production by preovulatory follicles (p less than 0.01), but secreted prostanoid levels did not differ significantly among different concentrations of GnRH agonists. Meiotic maturation of follicle-enclosed oocytes following GnRH agonist exposure began 2 hours earlier than production of PGs. PG production stimulated by GnRH agonists was reduced significantly by indomethacin. However, oocyte maturity in the presence of GnRH agonist plus indomethacin did not differ significantly from that of GnRH agonist alone. GnRH agonistic analogues induce the resumption of meiosis in follicle-enclosed oocytes in rabbits by a mechanism other than PG stimulation.

Animals↗

Inactivation of chemotactic activity of C5a by the serratial 56-kilodalton protease.

The effects of the 56-kilodalton protease (56K protease) from Serratia marcescens on complement-derived chemotactic activity were examined. Fresh human serum was incubated with zymosan to produce C5a. This activated serum was then incubated with various concentrations of 56K protease, and the chemotactic activity of mouse peritoneal exudate polymorphonuclear leukocytes (PMN) and macrophages was evaluated. A significant dose-dependent decrease of chemotactic activity was observed after protease treatment. Furthermore, treatment of human recombinant C5a with 56K protease at a dose of 1.0 microgram/ml resulted in a complete loss of chemotactic activity. When the living bacteria of the virulent strain, which produced about 10 times more protease than did the less virulent strain, were injected intraperitoneally into mice, the magnitude of infiltration of polymorphonuclear leukocytes into the peritoneal cavity was much lower than that caused by the less virulent strain. Because complement-dependent chemotactic activity is an initial response to bacterial infection, these results suggest indirect pathogenic functions of serratial proteases that suppress chemotactic activity.

Blood Bactericidal Activity↗

Dependence on O2- generation by xanthine oxidase of pathogenesis of influenza virus infection in mice.

We evaluated various biochemical parameters in influenza virus-infected mice and focused on adenosine catabolism in the supernatant of bronchoalveolar lavage fluid (s-BALF), lung tissue, and serum (plasma). The activities of adenosine deaminase (ADA) and xanthine oxidase (XO), which generates O2-, were elevated in the s-BALF, lung tissue homogenate, and serum (plasma). The elevations were most remarkable in s-BALF and in lung tissue: We found a 170-fold increase in ADA activity and a 400-fold increase in XO activity as measured per volume of alveolar lavage fluid. The ratio of activity of XO to activity of xanthine dehydrogenase in s-BALF increased from 0.15 +/- 0.05 (control; no infection) to 1.06 +/- 0.13 on day 6 after viral infection. Increased levels of various adenosine catabolites (i.e., inosine, hypoxanthine, xanthine, and uric acid) in serum and s-BALF were confirmed. We also identified O2- generation from XO in s-BALF obtained on days 6 and 8 after infection, and the generation of O2- was enhanced remarkably in the presence of adenosine. Lastly, treatment with allopurinol (an inhibitor of XO) and with chemically modified superoxide dismutase (a scavenger of O2-) improved the survival rate of influenza virus-infected mice. These results indicate that generation of oxygen-free radicals by XO, coupled with catabolic supply of hypoxanthine from adenosine catabolism, is a pathogenic principle in influenza virus infection in mice and that a therapeutic approach by elimination of oxygen radicals thus seems possible.

Adenosine↗

The effects of lipoxygenase products on progesterone and prostaglandin production by human corpora lutea.

The present study was undertaken to assess the effects of the products of the lipoxygenase pathway on steroidogenesis and the production of prostaglandins (PGs) by human corpora lutea in the midluteal phase. In the first experiment luteal cells were cultured with 5-hydroxyeicosatetraenoic acid (5-HETE) at 10, 100, 500, or 1000 ng/mL in the presence or absence of hCG at 100 ng/mL for 10 days. The addition of 5-HETE dose-dependently inhibited progesterone (P) production by the cultural luteal cells. P production stimulated by exposure to hCG was also reduced significantly in response to 5-HETE. However, 5-HETE had no effect on the production of 6-keto-PGF1 alpha, PGF2 alpha, or PGE2 by cultured luteal cells at any point during the culture period. In the second experiment the reaction products of soybean lipoxidase of arachidonic acid (AA-LIP) were added to cultured luteal cells. Treatment with either AA or LIP alone had no effect on basal P production. The addition of AA-LIP at all concentrations tested reduced P production by cultured luteal cells in the presence or absence of hCG. AA-LIP significantly reduced basal 6-keto-PGF1 alpha secretion in cultured luteal cells on day 2. Although the stimulatory effect of AA on luteal PGE2 production was maintained throughout the entire culture period, the lipoxygenase products of AA did not affect AA-stimulated PGE2 production by cultured luteal cell. These results suggest that the products of the lipoxygenase pathway may be important in the involution of human corpora lutea.

Adult↗

The effect of the follicular fluid adenosine 3',5'-monophosphate degradation rate on successful fertilization and cleavage of human oocytes.

Follicular fluid (FF) and oocytes were obtained from 19 women for in vitro fertilization. Ovulation was induced with clomiphene citrate and human menopausal gonadotropin. Thirty-seven FF samples containing mature oocyte-corona-cumulus complexes were used to measure steroids, gonadotropins, and cAMP. The FF specimens were divided into three groups: follicles yielding ova that were fertilized and cleaved (group A), follicles containing fertilized ova without further cleavage (group B), and follicles containing nonfertilized oocytes (group C). The FF levels of progesterone, 17 beta-estradiol, LH/hCG, and FSH did not differ significantly among the groups. Mean FF cAMP concentrations declined from 17.5 +/- 2.5 pmol/mL 15 min after follicle aspiration to 3.6 +/- 0.9 pmol/mL after 3 h. The initial FF cAMP concentration did not differ significantly among three groups. However, the cAMP degradation rate in group A (119 +/- 13 X 10(-4) pmol/min) was significantly greater than that in group B (62 +/- 10 X 10(-4) pmol/min) or group C (75 +/- 8 X 10(-4) pmol/min). In conclusion, an increased intrafollicular cAMP degradation rate was associated with successful fertilization and cleavage of human oocytes in vitro. These data suggest that the degradation rate of FF cAMP may be a marker of optimal follicular development and oocyte maturation.

Adult↗

Evidence of intercalation of trans-diethylstilbestrol and its methyl ether derivatives in multibilayers of egg phosphatidylcholine by high-power deuterium nuclear magnetic resonance (2H-NMR) spectroscopy.

The mode of incorporation of 2H-labeled trans-diethylstilbestrol (DES) (1b) and its methyl ether derivatives (2a, 2b, and 3) into multibilayers of egg phosphatidylcholine was analyzed by means of deuterium nuclear magnetic resonance. A clear distinction was found between DES or its methyl ether derivatives incorporated into lipid bilayers and those precipitated in the aqueous phase, by taking into account the extent of the motionally averaged quadrupole interaction. Thus, it was found that the relative proportion of these compounds incorporated into multibilayers decreased in the following order: DES (1b) greater than DES monomethyl ether (2a and 2b) greater than DES dimethyl ether (3). In addition, we demonstrated that the mode of intercalation in the multibilayers differs greatly among these compounds.

Deuterium↗

Effect of meso-hexestrol, a synthetic estrogen, on S-tubulin.

We have reported that meso-hexestrol, a synthetic estrogen, inhibits microtubule assembly and induces microtubule proteins into twisted ribbon structures. On the other hand, Serrano et al. proved that S-tubulin, which lacks the C-terminal moiety of tubulin subunits, assembles into sheet structures in the absence of microtubule-associated proteins (MAPs). In the present investigation, we attempted to clarify whether meso-hexestrol could induce the ribbon structure from S-tubulin. meso-Hexestrol delayed the initiation of polymerization of S-tubulin into sheet structures in a dose-dependent manner below 50 microM. But the effect of meso-hexestrol on S-tubulin was reduced in the presence of either tau or microtubule-associated protein 2 (MAP2) in a MAPs-concentration-dependent manner. At concentrations higher than 100 microM, meso-hexestrol inhibited the polymerization of S-tubulin into sheet structures, without forming ribbon structures. The present results may indicate that moso-hexestrol interacts with S-tubulin, and its interaction is affected by MAPs.

Animals↗

Regio- and stereoselective hydrogenation of 2'-demethoxy-2'-methyldehydrogriseofulvin, a symmetrical substrate, to (+)-2'-demethoxy-2'-methylgriseofulvin with a cell-free system of Streptomyces cinereocrocatus.

Enzymatic hydrogenation of 2'-demethoxy-2'-methyldehydrogriseofulvin (5) with a cell-free system of Streptomyces cinereocrocatus afforded (+)-2'-demethoxy-2'-methylgriseofulvin (6). The structure of 6 was determined on the basis of comparisons of the proton nuclear magnetic resonance spectrum, mass spectrum, and circular dichroism with those of a standard specimen which was synthesized chemically. The results demonstrated that when the 2'-position of (-)-dehydrogriseofulvin was substituted with a methyl group, its hydrogenation with the cell-free system occurred stereoselectively at the 5',6'-position.

Griseofulvin↗

Isolation and purification of a low molecular weight protein from bovine urine.

A low molecular weight protein was separated from urine samples obtained from a heifer with spontaneous renal disease and from cows with CaNa2EDTA-induced renal dysfunction. The molecular weight and electrophoretic mobility of the separated protein were examined. The low molecular weight protein collected by gel filtration chromatography was further separated into two fractions by ion exchange chromatography using DEAE-cellulose. One of the two fractions, the lowest molecular weight protein showed a single band in SDS-PAGE, and its molecular weight was approximately 12,000. An antiserum against this protein formed a single precipitin line with the urine from cows with experimentally induced renal dysfunction and a heifer with spontaneous renal disease by the double immunodiffusion technique. However, the antiserum did not form any precipitin line with the concentrated urine of healthy cow and human beta 2-microglobulin. In cellulose acetate membrane electrophoresis, this protein migrated in the same position as that of serum gamma-globulin from healthy cow.

Animals↗

An experimental model for advanced ovarian cancer.

Intraperitoneally transplanted tumors implanted and began developing with ascites in about 62% of the female rats within 4 to 6 weeks after transplantation. The tumor used in this study was an adenocarcinoma and which originated from a primary ovarian cancer in rats of the same strain (Wistar). The morphology and biological behavior of the tumor were very similar to the tumor in humans. Moreover, the preliminary results with cisplatin therapy indicate that intraperitoneal cancer corresponding to stage III or IV in the FIGO classification is a promising model for experimental therapeutic studies of common epithelial carcinoma at an advanced stage.

Animals↗

Cryogenic preservation of low-quality human semen.

The article describes the technical strategies for clinical cryogenic preservation of low-quality human semen. To compensate for sperm dilution resulting from the use of a cryogenic medium, ejaculated semen was concentrated before freezing by means of continuous-step density gradient centrifugation. Freezing was simplified by employing the carbon dioxide pellet method with KS-II cryogenic medium, which contains Pluronic F-68, a nonionic detergent, to solubilize egg yolk (a major cryogenic protectant). Semen of less than 50% motility (n = 23) was processed and then cryogenically preserved. Sperm concentration was increased by a factor of 1.8 +/- 0.96 (n = 23). Sperm motility was improved from 35.9% +/- 13.9% to 69.4% +/- 10.8%. Even after thawing 59.4% +/- 17.5% motility remained, with a mean survival rate of 85% +/- 14%. The concentration of sperm and improved sperm motility by the use of the continuous-step density gradient and the high survival rate ensured by the carbon dioxide pellet method with KS-II cryogenic medium compensated for the lowering of sperm quality during cryogenic preservation.

Centrifugation, Density Gradient↗