[Proteins C,S and C4bp--their structures and functions].
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Carrier Proteins↗
Biomedical subjects
S Horie
Publications and source records attributed to S Horie.
[A successful treatment of patient with paraquat poisoning].
A 60-year-old man was admitted 1 hour after ingesting approximately 40 ml of Gramoxon (paraquat) in an attempt to commit suicide. Gastrointestinal lavage, compulsory urination, and direct hemoperfusion (DHP) were immediately performed to remove the paraquat. He was then administered Vitamin E and high dose methylprednisolone therapy to prevent lung injury. Chest roentgenogram on the 3rd day showed ground glass appearance in the outer zone of bilateral lung fields. Chest CT scans on the 9th day revealed a faint high density area in the same area, suggesting interstitial change. The shadows gradually improved and had disappeared on the 35th day after admission. Serum superoxide dismutase (SOD) activity, measured by electron spin resonance spectroscopy, was undetectably low until the 22nd day, and then increased into the normal range. It was suggested that SOD was consumed to neutralize the paraquat toxicity. Serum SOD activity changed according to the paraquat activity, and was a useful indicator of paraquat toxic activity. He was discharged without any symptoms 50 days after admission.
Female↗
Purification and properties of cytochrome P-450 (SCC) from pig testis mitochondria.
Cytochrome P-450 was purified from pig testis mitochondria to a specific content of 13.1 n mol/mg of protein. The purified preparation was found to contain a single species of P-450, on sodium dodecyl sulfate polyacrylamide gel electrophoresis, with an apparent molecular weight of about 53000 +/- 2000. The cholesterol side chain-cleavage system could be reconstituted by mixing the purified cytochrome P-450, adrenodoxin reductase, adrenodoxin, cholesterol and NADPH. The rate of conversion of cholesterol to pregnenolone was 6.2 n mol/min/n mol of P-450 under the conditions employed. The absorption spectrum of the oxidized cytochrome P-450 had maxima at 416, 530 and 568 nm. The reduced CO-complex of the cytochrome P-450 exhibited an absorption maximum at 448 nm. The purified P-450 was subjected to microsequence analysis and its NH2-terminal amino acid sequence was found to show considerable homology with that of bovine adrenal P-450 (SCC).
Amino Acid Sequence↗
Characteristics of induction of peroxisomal fatty acid oxidation-related enzymes in rat liver by drugs. Relationships between structure and inducing activity.
To clarify the mechanism of induction of hepatic peroxisome-associated enzymes by drugs, we examined the interrelationship between the structures of fifteen drugs of two types (phenoxyacetic acid derivatives and perfluorinated compounds) and their inducing activities. Male Wistar rats were given the drugs at 150 mg/kg body weight daily for 2 weeks, and then hepatic activities of fatty acid metabolism-related enzymes were determined. The activity of the cyanide-insensitive fatty acyl-CoA oxidizing system located in peroxisomes was increased significantly in the following order: 2,4,5-trichlorophenoxypropionic acid (12.5-fold) greater than 2,4-dichlorophenoxypropionic acid (6.6-fold) greater than clofibrate (4.5-fold) greater than 2-methyl-4-chlorophenoxyacetic acid (2.6-fold) greater than 2,4,5-trichlorophenoxyacetic acid (2.5-fold) greater than p-chlorophenoxypropionic acid (2.4-fold) greater than 2,4-dichlorophenoxyacetic acid (1.7-fold). Treatment with perfluorinated compounds, perfluorobutyric acid, perfluorooctanoic acid, perfluorodecanoic acid and perfluorooctanol, also induced the activity by 2-, 4.3-, 3.1- and 2.0-fold respectively. The profile of the induction of carnitine acetyltransferase by these compounds was quite similar to that of cyanide-insensitive fatty acyl-CoA oxidizing system. Lipophilicity of these drugs was determined by the octanol-water partition method. Among these drugs, 2,4,5-trichlorophenoxypropionic acid showed the largest octanol/water partition coefficient (log P = 0.39). These results show a strong correlation among the number of chlor-substitutions on the phenyl moiety, the methyl-group on the alpha position of the acetic acid moiety, lipophilicity and the inducibility of peroxisomal fatty acid oxidation-related enzymes.
Animals↗
Comparison of the multiple molecular forms of bovine adrenocortical P450scc with those of corpus luteum P450scc.
1. Bovine adrenocortical P450scc was resolved into several fractions by chromatography on AH-Sepharose 4B followed by gel filtration on Toyopearl HW55S. All fractions contained P450scc of the same molecular size and the P450scc could be resolved into 3-4 major and more than 10 minor isoelectric point forms by isoelectric focusing on polyacrylamide gel in the presence of Emulgen 913. 2. Both the AH-Sepharose chromatography profile and the isoelectric focusing pattern of the adrenocortical P450scc were more complex than those of the corpus luteum P450scc. The corpus luteum P450scc was practically devoid of the neutral to acidic isoelectric point forms. 3. Three to four P450scc subfractions with different isoelectric focusing pattern were obtained from a purified preparation of adrenocortical P450scc by ion-exchange chromatography on DEAE-Toyopearl 650S or DEAE-Sephadex A25. These P450scc subfractions showed essentially the same spectral properties, catalytic activity, molecular weight and N-terminal amino acid sequence. 4. The most acidic (the latest eluting) subfraction was composed mostly of the neutral to acidic isoelectric point forms. The sedimentation characteristics of this subfraction was also studied. 5. The structural basis of the multiple molecular forms was discussed.
Adrenal Cortex↗
Induction of hepatic peroxisomes by a new, non-carboxylate-containing drug, bifonazole.
The acute effect of an antimycotic drug, bifonazole, on hepatic peroxisomes of rats was studied in comparison with that of clotrimazole, which has a similar structure. By feeding 0.5% bifonazole in the diet for 5 days, the activities of carnitine acyltransferase, carnitine palmitoyltransferase and the peroxisomal beta-oxidation system were increased by 30-, 3- and 7-fold, respectively, over the control. Under the same conditions, clotrimazole did not cause such changes. Electron microscopic observation showed that peroxisome proliferation had been induced by bifonazole treatment. Thus, a compound which does not contain a carboxylate moiety can induce peroxisomes in rodent liver.
Animals↗
Ca2+ channel blocking effects of hirsutine, an indole alkaloid from Uncaria genus, in the isolated rat aorta.
Ca2+ channel blocking activity of hirsutine and its pharmacological features were studied. Hirsutine (10(-6) to 3 x 10(-5) M) produced a dose-dependent relaxation of the isolated rat aorta contracted by norepinephrine and high K+ concentration. This effect was exhibited in the aorta strips with or without the endothelium, suggesting an involvement of vasodilative mechanisms not dependent on the endothelium. Hirsutine also inhibited the contractions induced by serotonin and Ca2+ channel activator YC-170, but not by Ca2+ ionophore A23187. The pA2 value of hirsutine was 6.6 +/- 0.1 (mean +/- S.E.; n = 4) in antagonizing cumulative dose-response curve for Ca2+ in the depolarized aorta strips. It is concluded that hirsutine apparently exhibits Ca2+ channel blocking activity mainly through inhibition of the voltage-dependent Ca2+ influx.
Alkaloids↗
Differential regulation of Na/H antiporter by acid in renal epithelial cells and fibroblasts.
Increased Na/H antiporter activity has been demonstrated after in vivo chronic metabolic acidosis as well as in vitro acid preincubation of cultured rabbit renal tubule cells. To study the underlying molecular mechanisms of this adaptive increase in Na/H antiporter activity, the present studies examined the effect of low pH media on Na/H antiporter activity and mRNA abundance in cultured renal tubule cells. Na/H antiporter activity was increased by 60% in a mouse renal cortical tubule cell line (MCT), and by 90% in an opossum kidney cell line (OKP) after 24 h of preincubation in acid (low [HCO3]) media. The ethylisopropylamiloride sensitivity of the Na/H antiporters were different in these two cell lines (MCT IC50 = 65 nM; OKP IC50 = 4.5 microM). In MCT cells, Na/H antiporter mRNA abundance measured by RNA blots increased by two- to fivefold after 24 h in low [HCO3] media. Na/H antiporter mRNA abundance was also increased in MCT cells with high CO2 preincubation as well as in rat renal cortex with in vivo chronic acid feeding. In contrast to renal epithelia, acid preincubation of NIH 3T3 fibroblasts led to suppression of Na/H antiporter activity. RNA blots of 3T3 fibroblasts revealed the same size Na/H antiporter transcript as in MCT cells. However, Na/H antiporter mRNA levels were suppressed by acid preincubation. These studies demonstrate differential regulation of Na/H antiporter activity and mRNA abundance in renal epithelial cells and fibroblasts in response to an acidotic environment.
Acidosis↗
Characteristics of peroxisome proliferation: co-induction of peroxisomal fatty acid oxidation-related enzymes with microsomal laurate hydroxylase.
The profile of the changes in the peroxisomal fatty acid oxidation activity in rat liver was compared with that in microsomal omega-oxidation under various conditions such as a 2-week administration of phenoxyacetic acid derivatives and perfluorinated compounds, short and long-term administration of clofibrate and bezafibrate, high-fat diet feeding, starvation and diabetes. The results were summarized as follows: 1) when phenoxyacetic acid derivatives and perfluorinated compounds were administered, there was a significant correlation in the increase of the activities between peroxisomal fatty acid oxidation and microsomal omega-oxidation. 2) On the long-term administration (79 weeks) of peroxisome proliferators the activities of the enzymes were significantly reduced, but the levels were still higher than the control level in a similar manner. 3) On high-fat diet feeding the patterns of the changes in the activities of peroxisomal fatty acid oxidation, carnitine acetyltransferase and microsomal omega-oxidation were similar to each other, differing from the changes in the activities of microsomal aminopyrin demethylase and mitochondrial carnitine palmitoyltransferase. 4) Under starved and diabetic conditions, co-induction of peroxisomal fatty acid oxidation and microsomal omega-oxidation was observed. From these results it is suggested that 1) the biosynthesis of these enzymes would be regulated on the gene expression of the nearby domain and 2) peroxisomal fatty acid oxidation and microsomal omega-oxidation were co-operatively regulated in order to achieve fatty acid metabolism smoothly.
Animals↗
Studies on aldose reductase inhibitors from natural products. IV. Constituents and aldose reductase inhibitory effect of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas.
The hot water extracts of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas, were found to have potent inhibitory activity towards lens aldose reductase (AR). Ellagic acid (4) was isolated from C. morifolium and I. batatas, isoscutellarein (7) from B. orellana and 3,5-dicaffeoylquinic acid (10) from I. batatas, respectively, as potent inhibitors.
Aldehyde Reductase↗
[Abdominal metastasis of a pineal region tumor through ventriculoperitoneal shunt. Case report].
An 18-year-old male was admitted with headache, nausea, and vomiting. Computed tomography (CT) revealed an enhanced tumor of the pineal region and hydrocephalus. The tumor was partially resected via a parieto-occipital craniectomy. The histological diagnosis was germinoma. No serum tumor markers such as alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were detectable. A ventriculo-peritoneal (V-P) shunt was emplaced and radiation therapy (whole brain 59 Gy) given. The tumor and the hydrocephalus regressed completely and he returned to work. Six years later, he experienced constipation and general fatigue. CT and echotomography of the abdomen showed a large peritoneal tumor and ascites. Laboratory investigation demonstrated serum levels of AFP 7640 ng/ml and HCG 150 IU/l, and high ascitic levels of AFP 12,890 ng/ml and HCG 1030 IU/l. AFP and HCG levels regressed after combined chemotherapy. However, he died due to leukopenia and pneumonia. Autopsy found no metastasis of tumor cells to the central nervous system. The peritoneal cavity contained hemorrhagic fluid and a large tumor 4100 g in weight. The tip of the V-P shunt tube was in front of the tumor. No neoplasm was found in the testis, retroperitoneal cavity, thymus, and other organs. The microscopic appearance of the peritoneal tumor was different to the first pineal tumor. The neoplasm was confirmed as a mixed germ cell tumor with teratoma components and suspected to be a metastasis of the pineal tumor through the V-P shunt system.
Abdominal Neoplasms↗
Chronic adaptations in proximal tubular H/HCO3 transporters.
Chronic acidosis, chronic K deficiency, and chronic hyperfiltration all lead to similar parallel increases in Na/H antiporter and Na/3HCO3 cotransporter activities. These effects persist when the transporters are removed from the inducing environment, and thus represent memory effects. The effect of acidosis on the Na/H antiporter can be reproduced by preincubating cultured proximal tubule cells chronically in acid media, suggesting that low extracellular fluid pH is an important signal in acidosis. The specific extracellular signals in chronic K deficiency and chronic hyperfiltration have not been elucidated. The effect of acid preincubation on Na/H antiporter activity in cultured proximal tubule cells is dependent on protein synthesis and is associated with increased abundance of mRNA for the Na/H antiporter. The cell signalling pathways which mediate these effects have not been determined. However, the common response in chronic acidosis, chronic K deficiency, and chronic hyperfiltration to the demand for increased H transport, suggests that a common signalling pathway will be found in all these conditions.
Adaptation, Physiological↗
[A case of surgically treated tuberculous aneurysm of descending thoracic aorta with massive hemoptysis].
A tuberculous aneurysm of the thoracic descending aorta was found in a 60-year-old female with massive hemoptysis. She had had lung tuberculosis one and half years ago. Computed tomography and aortic angiography revealed saccular type aneurysm at left supradiaphragmatic portion of descending aorta. After antituberculous chemotherapy, the aneurysm was resected under the temporary bypass support utilizing Bio-pump and the aorta was grafted with Dacron prosthesis successfully. The microscopic findings of specimens over the aneurysm and surrounding tissues revealed tuberculosis. The patient is doing well one year after the operation.
Aorta, Thoracic↗
[Catheter-in-catheter replacement technique for bronchial arterial continuous infusion therapy for pulmonary malignancies].
The purpose of this study was to improve tumor effects and to reduce side effects caused by one shot bronchial arterial infusion therapy for pulmonary malignancies. The catheter-in catheter replacement technique in proper bronchial artery was introduced for infusion therapy for several hours for this purpose. Three kinds of combination of catheters were selected and the duration of replacement in bronchial artery was either eight or 24 hours. In eight patients of 12 patients with pulmonary malignancies superselective bronchial arterial infusion was carried out through the inner small catheter. No significant complications developed either at the time of replacement or during continuous infusion.
Adult↗
[A clinical study of advanced cases of small sized lung cancer].
Survival rates and several effective factors for the postoperative course of 10 advanced cases of small sized lung cancer (ASLC) were evaluated. Followings were considered as characteristics of these patients: 1) ASLC were observed at the rate of 4.0% of whole lung cancers, 2) ASLC were more often seen in relatively young patients, females and adeno carcinomas than ordinary lung cancer, 3) as factors concerned to postoperative prognosis, stage III A (especially T1N2M0), few numbers of metastatic lymph nodes in N2, and performance of relative curative operation may predict good prognosis, but adenosquamous type will be a sign of poor prognosis. Satisfactory result was obtained even in a case of stage IV when complete resection of metastasis was carried out. There was no significant difference of survivals between 2 cm and 3 cm of diameter of the tumor. In conclusion, above mentioned points should be considered when operative indication of ASLC is evaluated.
Adenocarcinoma↗
Heparin-like glycosaminoglycan is a receptor for antithrombin III-dependent but not for thrombin-dependent prostacyclin production in human endothelial cells.
Antithrombin III (ATIII) induced a marked increase in prostacyclin (PGI2) release from cultured human umbilical vein endothelial cells (HUVEC) after incubation for more than 2 hr and the induction continued for 8 hr, while thrombin induced the increase within 10 min. ATIII-dependent production of PGI2 was abolished by addition of heparin, but pretreatment of HUVEC with polyclonal antibody against thrombomodulin could not prevent the PGI2 productions by ATIII and thrombin. ATIII-dependent PGI2 production was significantly inhibited by pretreatment of HUVEC with beta-D-xylosides or heparitinase, though neither pretreatment affected thrombin-induced PGI2 production. After treatment of HUVEC with 1 micrograms/ml cycloheximide. ATIII-dependent PGI2 production was completely abolished. These results indicate that the mechanism of the induction of PGI2 production by ATIII involves heparin-like glycosaminoglycans on HUVEC and the stimulation of synthesis of a protein related to PGI2 production. The ATIII-induced PGI2 production is very different from that induced by thrombin.
Antibodies, Monoclonal↗
Cyclic AMP increases thrombomodulin expression on membrane surface of cultured human umbilical vein endothelial cells.
Dibutyryl-cyclic AMP (Bt2cAMP; final concentration 1-5 mM) or beraprost sodium (synthetic prostacyclin, 100 nM) enhanced the expression of thrombomodulin (TM; an anticoagulant factor of endothelial cells) on the membrane surface of cultured human umbilical vein endothelial cells up to 1.4 times over the control within 9 hrs after the treatment, while the expression fell below the control level at 12 hrs and thereafter. 8-Bromo-cAMP (final concentration 1-5 mM) or 3-isobutyl-1-methylxanthine (IBMX; an inhibitor of phosphodiesterase; final concentration 10-1000 microM) enhanced the expression of TM on the cell surface at 12 hrs after the treatment. The enhancement of TM expression caused by Bt2cAMP was inhibited by incubation with phorbol 12-myristate 13-acetate. These results suggest that cAMP stimulates expression of TM in the endothelial cells.
1-Methyl-3-isobutylxanthine↗
Changes in the activities of dihydroxyacetone phosphate and glycerol-3-phosphate acyltransferases in rat liver under various conditions.
Activities of enzymes relating to the acyl dihydroxyacetone phosphate (acyl DHAP) pathway were determined in rat liver under conditions known to elevate the peroxisomal beta-oxidation activity. In fasted and streptozotocin-induced diabetic rats, DHAP acyltransferase activity showed a small but significant increase, though the activities of glycerol-3-phosphate (GP) acyltransferase and alkyl DHAP synthase were not changed. After 2 weeks, feeding of 20% partially hydrogenated marine oil, the activity of DHAP acyltransferase also increased to 140% of the control. The feeding of 0.25% clofibrate and 2% di(2-ethylhexyl)phthalate (DEHP) increased the activities of both DHAP and GP acyltransferases by 2- to 3-fold, whereas alkyl DHAP synthase activity decreased under the same conditions. A fractionation study showed that the increases in the activities of DHAP acyltransferase and acyl/alkyl DHAP reductase in the liver of rats treated with DEHP occurred mainly in peroxisomes and microsomes, respectively. The phospholipid contents per mg protein of the isolated hepatic peroxisomes from rats were as follows (percent of the control): fasting, 62%; diabetic, 69%; high fat-diet, 89%; clofibrate-treated, 126%; DEHP-treated, 119%. These results suggest that glycerophospholipid metabolism might also be controlled by peroxisomal enzymes under physiological and pathological conditions.
Acyltransferases↗