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Biomedical subjects

T Ono

Publications and source records attributed to T Ono.

At least 937 records · Page 52Linked to original sources

Positive foci of glutathione S-transferase placental form in the liver of rats given furfural by oral administration.

We observed GST-P-positive liver foci in rats during the course of developing liver cirrhosis by oral administration of furfural, an organic solvent. Male Wistar rats were given furfural-containing diet (20-30 mg/kg diet) for 15-150 days, and killed 14 days after terminating furfural feeding. Immunohistochemical investigation of GST-P-positive liver foci which appeared in rats fed furfural for more than 30 days revealed an increase in number and size of the foci in proportion to the duration of furfural administration. Since furfural is known not to be carcinogenic in rats, this finding will be helpful to understand the enhancing effect of furfural-induced cirrhosis on chemical hepatocarcinogenesis.

Administration, Oral↗

Transcriptional regulation of F plasmid gene srnB: rifampicin-promoted in vitro readthrough of a terminator in the leader region.

srnB is an F-plasmid encoded gene, otherwise silent, whose expression is induced by added rifampicin, leading to the release of cellular Mg2+ and degradation of stable RNA. In the absence of rifampicin, transcripts from the srnB gene were relatively short. S1 nuclease mapping revealed that the short mRNA species terminated within the leader, at the 3' end of a potential stem-and-loop structure. A deletion in the stem-loop resulted in constitutive synthesis of the mRNA that extended beyond the termination site into the structural gene. Even with the wild-type gene, transcription continued beyond the terminator sequence in the presence of added rifampicin. Most of the transcripts synthesized in the presence of rifampicin were long enough to encode the srnB protein. We hypothesize from these results that RNA polymerase associated with rifampicin can read through the terminator to induce srnB expression.

Amino Acid Sequence↗

A case of temporal lobe astrocytoma associated with epileptic seizures and schizophrenia-like psychosis.

The clinical pictures of a left temporal lobe astrocytoma involving the hippocampal region showed a period of 27 years from ages 12 to 38 by epileptic seizures and a period of 9 years from 14 to 22 by schizophrenia-like symptoms and the following aggressive behavior during 16 years from ages 23 to 38. After a resection of the temporal lobe tumor sparing the hippocampus, transient delusions and aggressive behavior were observed. It might be considered that the hippocampus has the most suspectable relationship with the schizophrenia-like symptoms.

Adult↗

Acquired renal cysts in five-sixths nephrectomized rats: the roles of oxalate deposits in renal tubules and a renotropic factor.

The present study was undertaken to see if the oxalate deposits seen in renal tubules are a causative factor in the development of acquired renal cysts in chronic renal failure. Thirty 5/6 nephrectomized rats had free access to water containing 8 mg/ml of vitamin C (oxalate precursor) and 20 5/6 nephrectomized rats were given tap water without vitamin C. Oxalate deposits were found on microscopy in the renal tubules of vitamin C-treated rats in the 11th and 12th postnephrectomy months; however, acquired renal cysts were noted far in advance of the appearance of oxalate crystals. It has been suggested that the tubular dilatation seen in 5/6 nephrectomized rats is caused by an abrupt decrease in the functioning renal mass, leading to the production of a so-called 'renotropic factor'. However, oxalate deposits and renal tubular dilatation in oxalate-treated 5/6 nephrectomized rats preceded the renal tubular dilatation of untreated partially nephrectomized rats. In addition, these histological changes in the kidney were also seen in healthy rats which were given oxalate orally and subcutaneously. The present study suggested that the pathogenesis of acquired renal cysts is multifactorial. Renotropic factor may play an important role leading to nephron hyperplasia, but oxalate deposits in the renal tubules seem to be an important factor in the formation of these cysts.

Animals↗

Effect of vitamin C supplementation on renal oxalate deposits in five-sixths nephrectomized rats.

We have previously reported that hyperoxalemia can be aggravated by vitamin C supplementation in regular hemodialysis patients. The present study was undertaken to examine the validity of this observation in an experimental setting. Fifty five-sixths nephrectomized rats were divided into two groups: 30 rats were allowed free access to water containing 8 mg/ml of vitamin C (100-160 mg/100 g/24 h) and the remainder given tap water without vitamin C. The serum creatinine increased and the Hct decreased gradually; however, there was no difference between the two groups. Plasma vitamin C, oxalate and urinary oxalate levels were higher in the vitamin -treated group than the nontreated rats. Histological examination revealed glomerular and interstitial fibrosis and round cell infiltration as well as tubular cyst formation. Oxalate deposits in renal tubules were found only in vitamin C-treated rats with advanced renal failure. Nontreated animals with equally advanced renal impairment showed no oxalate deposits. These results confirm our previous clinical findings that vitamin C supplementation aggravates the secondary oxalosis of chronic renal failure.

Animals↗

Immunoelectron microscopic localization of fibrin-related antigen in human glomerular diseases.

The distribution of fibrin-related antigen (FRA) in glomeruli was examined by immunoelectron microscopy in 9 patients with idiopathic membranous nephropathy (MN), 8 patients with minimal-change nephrotic syndrome, and 10 patients with IgA nephropathy (IgA-N), using antisera against human gamma--chain, alpha-chain, mu-chain, and fibrinogen. Electron-dense reaction products of FRA were observed in the endothelium, subendothelium, and/or in electron-dense deposits (EDD). Among the three glomerular diseases, the amount of electron-dense reaction products of FRA in the endothelium was highest in MN. This suggests that coagulation occurs on the endothelium in MN. Although the mesangial EDD of IgA-N were intensely stained with reaction products of FRA, the staining was weak in the subepithelial EDD of MN. This suggests that FRA hardly penetrates into the subepithelial EDD in MN.

Antigens↗

Ultrastructural distribution of von Willebrand factor in human glomerular diseases.

The distribution of the von Willebrand factor (vWF) as the factor-VIII-related antigen in glomeruli was examined by immunoelectron microscopy in 10 patients with idiopathic membranous nephropathy (MN), 8 patients with minimal-change nephrotic syndrome (MCNS), and 11 patients with IgA nephropathy (IgA-N). Electron-dense reaction products of vWF were observed in the endothelium and mesangium in all specimens examined. However, they were not detected in subepithelial electron-dense deposits of MN. The amount of electron-dense reaction products of vWF in the endothelium was significantly higher in MN than that in MCNS or IgA-N. This finding suggests that the glomerular endothelium in MN is the site of the local activation of coagulation and platelet aggregation system in glomerular capillary wall lesions.

Glomerulonephritis, IGA↗

45,XO/46,X,dic(Yq) mosaicism in Turner's phenotype with endodermal sinus tumor of the ovary.

A case of a endodermal sinus tumor of the ovary in a patient with 45,XO/46,X,dic(Y) mosaicism is reported because of the rarity of the karyotype and condition. A 15-year-old girl was admitted to Yamagata University Hospital because of constipation for several days. Physical examination showed webbing of the neck, cubitus valgus and short stature. Her abdomen was bulging. Chromosomal analysis showed 45,XO/46,X,dic(Yq) mosaicism in karyotype. alpha-Fetoprotein and CA-125 in the serum were high. A left ovarian tumor was found by laparotomy; however, the right ovary was a streak gonad and the uterus was hypoplastic. An endodermal sinus tumor was diagnosed by a pathologist. After operation, cisplatin-vinblastin-bleomycin chemotherapy was instituted and the tumor marker went down. This patient is still healthy and under observation at the outpatient clinic.

Adolescent↗

Nilvadipine attenuates ischemic degradation of gerbil brain cytoskeletal proteins.

We have previously demonstrated that transient cerebral ischemia induces marked decreases in concentrations of cytoskeletal proteins and have suggested putative involvement of calpain in the decrease of microtubule-associated protein 2 (MAP2) content. We examine the effect of nilvadipine, a new calcium channel blocker, on protein degradation in gerbil brains after 5 minutes of bilateral carotid artery occlusion and compare this effect with those of nimodipine and nicardipine. By densitometric quantification of the electrophoretically separated soluble proteins, mean +/- SEM MAP2 content in the hippocampus (14.4 +/- 1.8 micrograms/mg protein) was depleted (5.4 +/- 0.5 micrograms/mg, p less than 0.01) 4 days after ischemia; this depletion was significantly inhibited by 1 or 10 mg nilvadipine/kg/day. MAP2 content was also depleted in vitro when normal nonischemic brain extract was incubated with calcium, but this degradation was not inhibited by the calcium channel blockers. Our results suggest that calcium channel blockers do not act directly on calpain but act at the calcium channels of neurons and may suppress activation of the enzyme and attenuate ischemic degradation of cytoskeletal protein. We found nilvadipine to be the most potent drug among those studied, and we believe it could be useful for the treatment of cerebral ischemia.

Animals↗

Enhancement of DNA synthesis of human epithelial carcinoma cells by acidic fibroblast growth factor.

Human epithelial cells that had grown out from a maxillary carcinoma were examined for their responsiveness to putative growth-controlling factors in a serum-free medium. Among the factors examined, bovine brain acidic fibroblast growth factor (FGF) at 1 to 10 ng/ml significantly promoted DNA synthesis of the cells in the presence of 5 U/ml heparin, whereas type beta transforming growth factor inhibited it in a dose-dependent manner. Fetal bovine serum at 0.6% inhibited DNA synthesis of the cells by approximately 15%, but no significant influence was observed at higher concentrations up to 10%. Epidermal growth factor, bovine pituitary gland FGF and basic FGF exhibited no significant effect on DNA synthesis of the cells. The present result suggests that acidic FGF, a known mitogen for endothelial cells, is also mitogenic for human epithelial cells derived from maxillary carcinoma.

Carcinoma↗

An experimental study on the pathway of iron transfer from macrophages to erythrocytes in rat liver.

In order to reveal the pathway of iron release from macrophages, a 59Fe-labelled ferric hydroxide-potassium polyvinyl sulfate complex (Fe-PVS) was injected intravenously into anemic rats and the level of radioactivity in the liver, spleen, bone marrow, blood plasma and red blood cells (RBC) was estimated at various time intervals after the injection. Histochemical observation of ferric iron and ferritin in the liver was also made on anemic rats treated using unlabelled Fe-PVS. Fe-PVS injection promoted the recovery of anemia causing a rapid increase in the RBC number, with activated erythropoiesis occurring in the spleen and bone marrow. Soon after the injection, most of the radio iron was found in the liver with a small amount in the circulating erythrocytes, bone marrow and spleen. The iron level in the liver decreased gradually with a rapid increase in the iron level of the erythrocytes which reached a very high level 6 days after the 59Fe-PVS injection. Histochemical observations showed a heavy deposition of ferritin in the Kupffer cells 3 days after Fe-PVS injection. This deposition was minimized after 6 days with an increase in the level of ferritin in the parenchymal cells in the central area of acini. The level of radioferritin estimated biochemically in the nonparenchymal cell fractions of the liver revealed that the level dropped by about one third approximately 3.5 days after the Fe-PVS injection, showing the stimulated ferritin release at this stage. Results indicate that Kupffer cells in the liver play an important role in ferritin synthesis from the phagocytized iron compounds and that the iron is supplied for erythroid cell proliferation.

Animals↗

Effects of temperature and endogenous factors in blood on concentrations of cyclosporin in plasma measured by high-performance liquid chromatography.

The effects of temperature, hematocrit (Hct), lipid level in plasma and cyclosporin A (CyA) level in whole blood on the concentration of CyA in plasma measured by high-performance liquid chromatography were studied in vitro. With rise in blood storage temperature before cells were removed, the concentration of CyA in plasma was increased in the temperature range between 10 degrees C and 37 degrees C, but was decreased between 4 degrees C and 10 degrees C. With rise in Hct, the concentration of CyA in plasma was decreased, and it was more markedly decreased at the blood storage temperature of 4 degrees C than at 37 degrees C. A lipid supplementation study showed that the concentration of CyA in plasma was increased with rise in plasma triglyceride level and in plasma cholesterol level at the storage temperature of 4 degrees C but not at 37 degrees C. Studies of the effect of CyA concentration in blood on the CyA distribution in blood demonstrated that the cellular/plasma concentration (C/P) ratio at low levels (less than 200 micrograms/ml) of plasma CyA ranged from 4 to 10 and was about 2 times higher than that at higher concentrations at 4 degrees C, but the ratio was relatively constant at 37 degrees C. The saturation capacity of the cellular fraction for CyA showed considerable individual variations, but there was no difference between the capacities at 4 degrees C and 37 degrees C. The separation of plasma after equilibration at 37 degrees C made it possible to avoid the variations in the distribution of CyA in whole blood associated with changes in Hct, lipid level in plasma and CyA level in whole blood, and to obtain a measurement reflecting the physiologically significant concentration of CyA in plasma.

Chromatography, High Pressure Liquid↗

A possible mechanism of fever induced by Nocardia rubra cell wall skeleton (N-CWS) in experimental animals.

The characteristics of fever elicited by the cell wall skeleton of Nocardia rubra (N-CWS) and by lipopolysaccharide (LPS) were compared in rabbits, and the possible involvement of the antigenicity of N-CWS was investigated in guinea pigs. In rabbits, fever of more than 0.5 degree C developed after an intravenous (i.v.) injection of 10 micrograms/kg or more of N-CWS, and was monophasic with 30-100 micrograms/kg but biphasic with the highest dose of 300 micrograms/kg. LPS elicited fever with similar characteristics at doses of 0.01-0.1 microgram/kg. With both compounds, the fever was inhibited by indomethacin. Tolerance to N-CWS and LPS appeared after dosing with 30 or 0.1 micrograms/kg, respectively for 10 d. In guinea pigs sensitized with N-CWS, challenge with 1 or 10 micrograms/kg of N-CWS 10 d later, which did not induce fever in the nonsensitized animals, caused fever of more than 0.5 degree C, and delayed-type hypersensitivity (DTH) appeared. N-CWS also elicited fever in nonsensitized guinea pigs bearing N-CWS-sensitized lymphocytes or anti-N-CWS antibody; the fever was higher in the guinea pigs sensitized with the lymphocytes than in those with the anti-N-CWS antibody. In brief, single injections of N-CWS and of LPS elicited fever with similar characteristics, although the potency of N-CWS was weaker. With N-CWS, the fever is proposed to be triggered by the antigenicity of the compound itself, because doses as low as 1 or 10 micrograms/kg elicited fever along with immunological response in N-CWS-sensitized animals, but not in nonsensitized ones.

Animals↗

Ozagrel hydrochloride monohydrate, a thromboxane synthase inhibitor, and its metabolites as inhibitors of hepatic microsomal drug metabolism.

The change in the hepatic oxidative drug-metabolizing capacity in humans treated with ozagrel hydrochloride monohydrate (OZA), an imidazole derivative and a new thromboxane A2 synthase inhibitor, was studied and the inhibitory potencies of the metabolites of OZA (M-1 and M-2) on the mouse hepatic microsomal monooxygenase system in vitro were compared with that of OZA. In vitro, M-1 and M-2, which are the beta-oxidized form and the reduced form of OZA, respectively, inhibited aminopyrine N-demethylation, aniline hydroxylation and testosterone hydroxylations in mouse hepatic microsomes and produced type II difference spectra in the same manner as OZA. The kinetic data indicated that the inhibitory potencies and the affinities of these compounds for cytochrome P-450 were decreased in the order of M-2 greater than OZA greater than M-1. The ratio of 6 beta-hydroxycortisol (6 beta-OHF) to cortisol (F) in urine, used as an indicator of oxidative drug-metabolizing capacity in humans, did not change significantly during oral treatment with 400 mg/d of OZA, while the ratio decreased to 80-85% of the original level during treatment with 800 mg/d of OZA. Although the participation of the metabolites of OZA in the reduction of drug-metabolizing capacity in vivo is not yet clear, the results suggest that hepatic oxidative drug-metabolizing enzyme activities in humans are inhibited by treatment with a relatively high dose of OZA.

Acrylates↗

[Effects of lithium deficient diet on avoidance behavior].

To determine whether lithium deficiency has an effect on lever-press avoidance behavior, low lithium diets were given to mice and the effects of these diets on conditioned lever press avoidance response were compared with that of a commercial diet containing 110 ng Li/g diet. Three low-lithium diets were prepared in this experiment and the lithium contents of the diets were 6.6, 36.6 and 76.6 ng Li/g diet. The mice used in this experiment had been maintained on a practical diet and trained by Sidman's situation previously. After checking that the conditioned response was established, they were divided into four groups. Three groups of mice each were given one of the low lithium diets, indicated above, and these were assigned into the lithium-deficient groups. Some mice were given the practical diet and this group was used as controls. The avoidance behavior was analyzed by the method reported previously by the authors. After changing the diet to a low-lithium one, the avoidance behavior was significantly suppressed in lithium-deficient groups and this appeared to be proportional to the level of lithium deficiency in the diet. Furthermore, this suppression in the avoidance behavior was recovered by lithium supplementation in the same experimental diet. These findings suggest that low-lithium intake may suppress acquired avoidance behavior in mice.

Animals↗

Relationship between number of asbestos bodies in autopsy lung and pleural plaques on chest X-ray film.

We investigated the relationship between number of asbestos bodies and pleural plaques. Using sodium hypochrolite, we examined 400 autopsy lungs and could detect 71 cases whose asbestos bodies were significantly high. We checked pleural plaques on chest x-ray films of these 71 cases and compared the exact plaque at autopsy. By the criteria of Askergren and Szamosi, we classified these into three groups (probable, definite, definite with calcification). This classification is consistent with the pleural plaques found at autopsy. Cases whose pleural plaques were definite (thick) had many more asbestos bodies than indefinite cases. As for occupational histories, there were 23 cases who worked in Japanese Naval shipyards before and during World War II, 14 others in various shipyards, and 14 others who also had a history of asbestos exposure. These 51 patients died more than 30 years after the first asbestos exposure. Twenty had no definite asbestos exposure.

Adult↗