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Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 901 records · Page 50Linked to original sources

A case of leiomyoblastoma (epithelioid leiomyosarcoma) of the greater omentum.

A 59-year-old male complained of a palpable abdominal mass which was revealed to be a primary omental tumor by means of abdominal ultrasonography, computed tomography, angiography and laparoscopy. Histological examinations of the surgically resected tumor further disclosed leiomyoblastoma with positive stainings of both vimentin and desmin, markers for mesenchymal cells and for muscle cells, respectively. He has been well for 2 years since resection, without any relapse or distant metastasis of the tumor. Leiomyoblastoma of the greater omentum is very rare, and is important to distinguish from extraluminal tumor of the abdomen.

Angiography↗

Characteristics of mutagenesis by glyoxal in Salmonella typhimurium: contribution of singlet oxygen.

The characteristics of mutagenesis by glyoxal in Salmonella tester strains TA100 and TA104, and particularly a possible role of active oxygen species, were investigated. Glyoxal was converted into a non-mutagenic chemical with glutathione (GSH) by glyoxalase I, and the mutagenic activity was enhanced by the depletion of intracellular GSH. Glyoxal caused the reduction of nitro blue tetrazolium, which was suppressed by the addition of 2,5-diphenylfuran, superoxide dismutase (SOD) and catalase (CAT), scavengers of singlet oxygen (1O2), superoxide radical (O2-) and hydrogen peroxide (H2O2), respectively. However, only the 1O2 scavenger almost completely suppressed the mutagenic activity of glyoxal. Mutagenicity assays using strains pretreated with N,N-diethyldithiocarbamate of a SOD inhibitor and strains with low levels of SOD and CAT indicated that the mutagenesis by glyoxal was independent of intracellular levels of SOD and CAT, though glyoxal itself repressed them. Therefore, all the results suggest that 1O2 formed from glyoxal is related to its mutagenesis, but that neither O2- nor H2O2 is intracellularly predominantly related to it. The action of glyoxal against SOD and CAT, and the formation of glyoxal adducts with amino acids as their components are also discussed.

Amino Acids↗

Effect of gamma-vinyl gamma-aminobutyric acid on the gamma-aminobutyric acid receptor-coupled chloride ion channel in vesicles from the brain of the rat.

The effect of gamma-vinyl GABA on the gamma-aminobutyric acid (GABA) receptor-coupled chloride ion (Cl-) channel was studied using membrane vesicles from cerebral cortex of the rat. gamma-Vinyl GABA, an antiepileptic drug, had no effect on uptake of 36Cl-, without preincubation. However, preincubation of membrane vesicles with gamma-vinyl GABA (100-1000 microM) produced a concentration-dependent decrease in net uptake of 36Cl-. No alteration was observed in basal uptake of 36Cl-. This decrease in net uptake of 36Cl- was not related to desensitization induced by endogenous GABA, which might be increased by gamma-vinyl GABA through selective, irreversible inhibition of GABA-transaminase (GABA-T). Concentration-response curves for GABA showed that preincubation with gamma-vinyl GABA inhibited GABA-stimulated uptake of 36Cl- with no change in ED50. These results indicate that gamma-vinyl GABA may act directly at the GABA/benzodiazepine ionophore complex, as a non-competitive antagonist of GABA.

4-Aminobutyrate Transaminase↗

Enterostatin (Val-Pro-Asp-Pro-Arg), the activation peptide of procolipase, selectively reduces fat intake.

Valine-proline-aspartate-proline-arginine (VPDPR), the amino terminal pentapeptide of pancreatic procolipase, produced a dose-dependent reduction in food intake when injected intraperitoneally into Osborne-Mendel rats that had been starved overnight. This inhibition of feeding was observed when the rats were fed a high-fat diet but not in rats fed a high-carbohydrate, low-fat diet. At higher doses of VPDPR, the inhibition of feeding was maintained for over 6 hours. An equimolar mixture of the free amino acids had no effect on food intake. In rats adapted to a three-choice macronutrient diet, VPDPR inhibited fat intake but had no effect on carbohydrate or protein intake. This selective inhibition of fat intake was observed in both overnight-fasted rats presented with food and in ad-lib-fed rats at the beginning of the dark-onset feeding period. It is suggested that this peptide may be a feedback signal to regulate the intake of dietary fat.

Animals↗

Pancreatic procolipase propeptide, enterostatin, specifically inhibits fat intake.

Pancreatic procolipase is activated by trypsin forming colipase, a cofactor for pancreatic lipase involved in intestinal fat digestion and a pentapeptide named enterostatin. Enterostatin with the sequence Val-Pro-Asp-Pro-Arg (VPDPR) was previously shown to decrease food intake in rats both after peripheral and central injection. In this work enterostatin has been shown to reduce specifically the consumption of a high-fat diet as opposed to a low-fat diet after central injection of Sprague-Dawley rats. After starvation for 18 hours the rats were given a free choice of a low-fat diet (5.2% fat by weight; 14.1% by energy) and a high-fat diet (17.8% fat by weight; 32.8% by energy) in separate containers. After injection of 200 ng of VPDPR into the lateral ventricle, the rats selectively decreased the intake of the high-fat diet by 45% (p less than 0.005), while the intake of the low-fat diet was unaffected compared to saline injection. VPDP after intracerebroventricular injection had totally lost the selective effect on the consumption of a high- fat and a low-fat diet. It is suggested that enterostatin formed during fat digestion from pancreatic procolipase may provide a feed-back signal for the intake of lipid.

Animals↗

Cellular response to oxidative damage in lung induced by the administration of dimethylarsinic acid, a major metabolite of inorganic arsenics, in mice.

Oral administration of dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenics, induces DNA damage in the mouse and rat lung due to both active oxygens and dimethylarsenic peroxyl radical produced in the metabolism of DMAA. Our paper describes the cellular response to DMAA in the mouse lung. In male ICR mice given a single po dose (1500 mg/kg) of DMAA-Na, the activities of mitochondrial superoxide dismutase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase significantly increased at 6 hr or longer after dosing, while cytosolic superoxide dismutase and catalase did not. With regard to cellular sulfhydryls after DMAA dosing, levels of reduced glutathione and nonprotein sulfhydryl decreased, while mixed disulfides significantly increased. Further, NADPH markedly decreased at 6-9 hr after DMAA dosing. These cellular variations suggest that the mouse pulmonary cell produced active oxygens, i.e., superoxide anion radical, hydrogen peroxide, and subsequent radicals in the metabolism of DMAA and that these and also the dimethylarsenic peroxyl radical were responsible for pulmonary DNA damage.

Administration, Oral↗

Protective effect of chromium(III) on acute lethal toxicity of carbon tetrachloride in rats and mice.

Trivalent chromium (Cr(III)) preadministered intraperitoneally (5 mg Cr/kg body weight) to rats and mice protected these animals from acute lethal toxicity of carbon tetrachloride (CCl4). Some other metals, Cr(VI), Cu(II), and Zn(II), had no effect on CCl4 lethal toxicity. DL-alpha-tocopherol, one of the antioxidative agents, showed similar protective effects to Cr(III). Activities of serum GOT and GPT in mice were increased sharply by the administration of CCl4, but these elevations were depressed by Cr(III) preadministration. Serum glucose levels of mice increased transiently after CCl4 administration and then in the control group fell to hypoglycemic levels after 6 hr, whereas the Cr(III)-pretreated group kept to homeostatic levels. Lipid peroxidation of microsomes in mice 24 hr after Cr(III) administration was lower than that of the control. These results suggest that Cr(III) preadministered to mice might act as a radical scavenger to CCl4 to form trichloromethyl radicals which are a major initial product of CCl4 in liver cells.

Animals↗

Chromium (III) decreases carbon tetrachloride-originated trichloromethyl radical in mice.

Effects of the administration of trivalent chromium (Cr(III)) to mice and the activation of carbon tetrachloride (CCl4) to form trichloromethyl radicals (.CCl3) in the liver were studied. The lipid peroxidation in liver microsomes induced in vitro by CCl4 in the presence of NADPH was decreased by the preadministration of Cr(III) to mice. The activity of NADPH-cytochrome C reductase, which presumably catalyzes the formation of .CCl3 from CCl4 in liver microsomes, was depressed by Cr(III) administration and kept at a level lower than that of the control group for at least 2 hr after CCl4 dosing. Furthermore, the frequency of appearances of ESR signals of .CCl3 in the liver homogenate of mice 1 min after CCl4 administration was markedly decreased by Cr(III) preadministration, similarly to DL-alpha-tocopherol. These results suggest that Cr(III) preadministered to mice decreases the formation of .CCl3 from CCl4, an activating process of CCl4, in the liver, presumably by scavenging the radical.

Animals↗

DNA lesion in rat hepatocytes induced by in vitro and in vivo exposure to glyoxal.

The alkaline elution technique was applied to measure the damage of rat hepatic DNA following exposure to glyoxal. DNA single-strand breaks were induced after exposure of primary-cultured hepatocytes to 0.1-0.6 mg/ml glyoxal for 60 min, while no DNA cross-link was observed. Single-strand breaks were also detected in livers of rats within 2 h following a single oral exposure at 200-1000 mg/kg body weight, and the frequency of the breaks reached a maximum around 9 h after exposure. The breaks were almost fully repaired 24 h after exposure to any dose. However, hardly any DNA lesions were detected in other tissues following exposure to 1000 mg/kg glyoxal. Thus, the present results indicate that glyoxal causes DNA single-strand breaks in rat hepatocytes following in vitro and in vivo exposure.

Administration, Oral↗

Subchronic oral toxicity of glyoxal via drinking water in rats.

The subchronic oral toxicity of glyoxal via drinking water and the effect on in vivo protein synthesis in tissues following a single treatment with this substance were assessed in Sprague-Dawley male rats. Animals received drinking water containing glyoxal levels of 2000, 4000, and 6000 mg/liter ad libitum for 30, 60, and 90 days in Phase I. In Phase II, the high-dose and control-1 groups fed the diet ad libitum, and a diet-limited control-2 group given the same amount of diet as consumed by the high-dose group were maintained for 90 and 180 days. The study designs included observations of clinical signs, body weights, major organ weights, gross and histopathological examinations, serum clinical chemistry, and biochemical examinations such as glyoxalase activity and glutathione content in selected tissues. Body weight gain and organ weights significantly decreased with dosage. Although consumption of food and water was also depressed in the exposed group, the reduction of body weight gain was greater in the high-dose group than in the diet-limited control 2 group. Histopathological examinations revealed only a slight papillary change in the kidneys from the high-dose group at both 90 and 180 days terminations in Phase II. The induction of both glyoxalase I and II was observed in liver and erythrocytes at 30-day termination of the exposed groups. Serum enzyme and protein levels were significantly reduced by the mid- and/or high-dose exposures. With a single oral high-dose treatment of glyoxal, a great decline in the incorporation of L-[3H]leucine was shown particularly in the liver, and this probably led in part to a reduction in the serum protein levels in rats following subchronic exposure to glyoxal. These data indicated an overall low degree of systemic toxicity to rats exposed subchronically to glyoxal via drinking water.

Animals↗

Toxicity of gentamicin in organ culture of fetal rat intestine.

The effect of gentamicin in the culture of fetal rat intestine was studied. Fetal rat intestine was cultured with gentamicin or kanamycin at the concentration between 4 to 200 micrograms/ml. Kanamycin did not have influence on lactase, maltase and ALP activities. On the other hand, gentamicin caused decrease of lactase and ALP activities at the concentration of 40 and 200 micrograms/ml compared with the activities at 4 micrograms/ml. Maltase activities did not decrease with gentamicin. Our data suggest that gentamicin could affect lactase and ALP activities and lower concentration should be used in the culture.

Alkaline Phosphatase↗

Antigenic analysis of feline coronaviruses with monoclonal antibodies (MAbs): preparation of MAbs which discriminate between FIPV strain 79-1146 and FECV strain 79-1683.

We prepared 31 monoclonal antibodies (MAbs) against either FIPV strain 79-1146 or FECV strain 79-1683, and tested them for reactivity with various coronaviruses by indirect fluorescent antibody assay (IFA). Sixteen MAbs which reacted with all of the 11 strains of feline coronaviruses, also reacted with canine coronavirus (CCV) and transmissible gastroenteritis virus (TGEV). In many of them, the polypeptide specificity was the recognition of transmembrane (E1) protein of the virus. We succeeded in obtaining MAbs which did not react with eight strains of FIPV Type I viruses (showing cell-associated growth) but reacted with FIPV Type II (79-1146, KU-1) and/or FECV Type II (79-1683) (showing non-cell associated growth). These MAbs also reacted with CCV or TGEV. These MAbs recognized peplomer (E2) glycoprotein, and many antigenic differences were found in this E2 protein. These results suggest that FIPV Type II and FECV Type II viruses are antigenically closer to TGEV or CCV than to FIPV Type I viruses. Furthermore, the MAb prepared in this study has enabled discrimination between FIPV strain 79-1146 and FECV strain 79-1683, which was thought to be impossible by the previous serological method.

Animals↗

Role of serum albumin as a carrier of 99mTc-complex to tumor tissue.

To elucidate a factor required for tumor-imaging 99mTc-labeled radiopharmaceuticals, in vivo behaviors of 99mTc-L-cysteine (99mTc-Cys) and 99mTc-2-mercaptoethylamine (99mTc-ME) were compared with that of 99mTc-DL-homocysteine (99mTc-Hcy) which had been found to accumulate in several experimental tumors. When these three complexes were intravenously injected into mice bearing Ehrlich solid tumor, their tumor affinity was found to depend on their binding ability to serum albumin; 99mTc-Hcy, the albumin-binding ability of which was highest of the three, was the most tumor-tropic. When the albumin-bound complexes of these three were injected, their tumor distributions were enlarged. These results suggest the importance of serum albumin in serving as a carrier for the transport of 99mTc-Hcy-related compounds to tumor tissue.

Animals↗

Congenital myotonic dystrophy with progressive edema and hypoproteinemia.

We report a patient with congenital myotonic dystrophy who had progressive edema and hypoproteinemia. An atrioseptal defect and patent ductus arteriosus were noted and were considered to be the cause of the right heart failure and edema. Although urinary protein levels were minimal, infusion of albumin did not improve the hypoproteinemia. Administration of dexamethasone increased the serum protein level, but the edema was not ameliorated. Autopsy revealed a slight lymphatic dilation in the small intestine, suggesting protein-losing enteropathy.

Autopsy↗

Post-irradiation treatment with OK432 can prevent radiation-induced bone marrow death.

The radioprotective effect of OK432, a Streptococcus haemolyticus preparation, on bone marrow death was examined in mice. The LD50 value was increased from 7.55 Gy in controls to 8.45 Gy in mice treated once with OK432 immediately after irradiation. Multiple administrations of the agent further elevated the LD50 value to 9.56 Gy. The radioprotective effect was also apparent when multiple treatments were commenced as late as 72 h after irradiation.

Animals↗

Nucleotide sequence of the genomic RNA of hepatitis C virus isolated from a human carrier: comparison with reported isolates for conserved and divergent regions.

The complete nucleotide sequence of a hepatitis C virus derived from plasma of a human carrier in Japan was determined. The cDNA of the isolate (HC-J6) contained 9481 nucleotides and an additional T stretch of 30 to 108 nucleotides at the 3' end, and had one large open reading frame coding for a polyprotein of 3033 amino acids. It differed by 31.8 to 32.1% in the nucleotide sequence and by 27.4 to 27.7% in the amino acid sequence from an American isolate and two Japanese isolates previously reported. Among these four isolates, the 5' non-coding region of 329 to 341 nucleotides was well conserved (greater than 93% identity), whereas the 3' non-coding region of 39 to 45 nucleotides (T stretches not included) was more variable (greater than 30% identity). An excellent degree of conservation of the 5' non-coding region would reflect its pivotal role in replication, and primers deduced from this region could be applied for the sensitive and specific detection of viral RNA by polymerase chain reaction. Due to a high degree of similarity in the amino acid sequence of the putative core protein (greater than 90%), antigen probes deduced from it would be suitable for the serological diagnosis of HCV infection. Low sequence similarity in the putative envelope protein (greater than 53% identity), however, would have to be taken into account in considering the immunoprophylaxis of HCV infection.

Amino Acid Sequence↗

Developmental process of the T-cell receptor alpha and delta gene assembly in B-cell precursor acute lymphoblastic leukaemia.

We analysed the organization of V delta genes and delta recombining element (delta Rec) in 27 children with B-cell precursor acute lymphoblastic leukaemia. Twenty-two of 54 alleles showed rearrangements of the T-cell receptor (TCR) delta locus. These rearrangements resulted either from D2D delta 3 (2 alleles) or V delta 2(Dn)D delta 3 (20 alleles) recombinations, and the other V delta and delta Rec were not rearranged. Of 23 alleles with deletion of C delta and rearrangements of J alpha, V delta 2, V delta 4 and V delta 5 appeared to rearrange to J alpha on five alleles. With regard to the relationship between the rearranged V alpha/delta and J alpha genes, gene segments 5' to V delta 2 frequently rearranged to J alpha more proximal to C alpha, whereas V delta 2 and gene segments 3' to V delta 2 showed a tendency to rearrange to J alpha distal to C alpha. Based on these findings, we suggest that the initial recombination event of the TCR-alpha/delta gene may be D2D delta 3 joining, followed by V delta 2 recombination with the D2D delta 3 complex. It was also suggested that use of V alpha/delta and J alpha/delta may depend on the distance between the involved V alpha/delta and J alpha/delta at least in B-lineage cells. These rearrangements in B-precursor cells appear to be aberrant. However, this recombinational process may be one of the normal differentiation pathways in T-lineage cells, because cells with a V delta 2(Dn)D delta 3 rearrangement were detected in 0.1-0.01% of normal peripheral mononuclear cells by the polymerase chain reaction.

Base Sequence↗