Biomedical subjects
Publications and source records attributed to T Watabe.
Morphology of vitrified Sendai virions was studied by transmission type electron microscopy. Almost all the virions appeared to be completely spherical, although their diameters differed. A possibly continuously long nucleocapsid was seen running helically in an envelope. Spikes were seen on the virion surfaces. The results indicate pleomorphism of Sendai virions in size but not in shape.
Exogenously administered vasopressin (VP) augments ACTH secretion stimulated by CRH. This study was performed to elucidate the role of endogenous VP in potentiating CRH-induced ACTH secretion in man. Synthetic human CRH (100 micrograms) was injected iv into seven normal men after they had been water loaded (20 mL/kg; 60 and 30 min before CRH injection; WL-CRH test) and water deprived (water restriction for 18 h before CRH injection; WD-CRH test). Blood samples were obtained before and 5, 15, 30, 60, 90, and 120 min after CRH injection at 0900 h for determination of plasma ACTH, cortisol, arginine vasopressin (AVP), CRH, and catecholamine levels and osmolality. Urine was obtained immediately before and 120 min after CRH injection for determination of osmolality. The mean plasma AVP levels were significantly higher during the WD-CRH test [1.8 +/- 0.4 (+/- SE) to 1.9 +/- 0.4 pmol/L] than during the WL-CRH test (0.6 +/- 0.1 to 0.9 +/- 0.1 pmol/L). The mean plasma ACTH and cortisol levels rose significantly from basal (4.5 +/- 0.6 pmol/L and 320 +/- 20 nmol/L, respectively) to peak values of 14.0 +/- 2.1 pmol/L at 30 min and 700 +/- 50 nmol/L at 60 min, respectively, during the WD-CRH test. During the WL-CRH test, mean basal plasma ACTH and cortisol levels were 3.5 +/- 0.7 pmol/L and 420 +/- 50 nmol/L, respectively, and reached peak values of 7.7 +/- 1.1 pmol/L at 60 min and 550 +/- 40 nmol/L at 30 min, respectively. Both the mean peak levels and integrated ACTH and cortisol responses were significantly higher during the WD-CRH than during the WL-CRH test. There was no significant difference between the plasma CRH and catecholamine concentrations in both tests. These results suggest that endogenous AVP potentiates CRH-stimulated ACTH secretion and, thus, plays a physiologically significant role in regulating CRH-stimulated ACTH and cortisol secretion in man.
Very little has been known of the biochemical function of a human adrenocortical carcinoma cell line, SW-13. In this study, the production of several adrenal steroids and 3', 5'-cyclic adenosine monophosphate (cAMP) were investigated in this cell line. The cells were incubated in L-15 medium containing 0.1% bovine serum albumin with several reagents in an atmosphere of 5% CO2 and 95% air for 2 hours at 37 degrees C. Aldosterone (Ald), corticosterone (B), cortisol (F), dehydroepiandrosterone sulfate (DHEA-S) and cAMP were simultaneously assayed by specific radioimmunoassays in the medium and cells. Significant increases in cAMP production were observed by cholera toxin (10 ng/ml) and forskolin (10 nM), both direct stimulators of adenylate cyclase, in the cAMP concentration without an increase in the steroids. The DHEA-S concentration in the medium was significantly increased by angiotensin-II (10(-7)M), noradrenalin (3 X 10(-5) M), adrenalin (3 X 10(-5) M) or alpha-melanocyte-stimulating hormone (alpha-MSH, 10(-7) M), none of which was associated with cAMP production. Neither adrenocorticotropin (10(-10) M) nor human chorionic gonadotropin (500 mIU/ml) stimulated the release of the steroids or cAMP production. A calcium ionophore, A23187 (10(-7) M), and 12-O-tetradecanoylphorbol-13-acetate (10(-8) M), a direct stimulator of protein kinase C, stimulated the release of DHEA-S, but not those of Ald, B and F. The results suggest that SW-13 retains functioning adenylate cyclase which, however, is not linked with steroidogenesis and that DHEA-S is produced probably by the mechanisms which involve protein kinase C system or calcium ion. This report provides the first demonstration of cAMP and DHEA-S production in SW-13 and suggests that this cell line is potentially useful for investigating the mechanisms of steroidogenesis in the human adrenal cortex.
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A case of multiple superficial temporal artery (STA) pseudoaneurysms following craniotomy is reported and a review of the literature is made. The patient was a 17-year-old male who was hospitalized as he developed right hemiparesis 4 hours after golf ball injury to the left temporal region. He had been diagnosed as hemophilia A one year prior to the injury. CT scan showed right parietal intracranial hematoma with mass effect when he was submitted to emergency craniotomy. At surgery a linear scalp incision was made over the left temporal area after high factor VIII concentrates (con-VIII), 2,000 units, were administered. His postoperative course was uneventful and hemiparesis improved substantially, however two pulsatile masses along the incision scar over the scalp were noticed some 40 days after the hematoma removal. There was another pulsating mass in the left wrist where an arterial cannulation was made at the time of craniotomy. Selective angiograms showed two left STA pseudoaneurysms and left radial pseudoaneurysm was also demonstrated. The left STA was embolized with Gelfoam pieces through catheterization after administration of con-VIII, and the radial artery aneurysm was surgically resected. There was no evidence of recurrence of these lesions during the follow-up period of eight months. Among over 130 cases of STA pseudoaneurysms reported, there was no case with hemophilia and also no such a case described which developed after craniotomy on reviewing the literature. And it was proved that con-VIII has enabled a patient to tolerate embolization procedure through catheterization.
Plasma corticotropin-releasing factor (CRF), corticotropin (ACTH) and cortisol levels were simultaneously determined by radioimmunoassays at 0600 h, 1200 h, 1800 h and 2200 h in six normal subjects, in order to examine whether the diurnal rhythm in plasma CRF exists and how it correlates to the diurnal rhythm in plasma ACTH and cortisol concentration. The highest CRF level was observed at 0600 h (7.0 +/- 1.2 pg/ml) and significantly lower levels (p less than 0.01) at 1800 h (1.7 +/- 0.2 pg/ml) and 2200 h (1.9 +/- 0.4 pg/ml). A clear diurnal rhythm was demonstrated in plasma ACTH and cortisol levels, with the highest values at 0600 h (44.6 +/- 8.1 pg/ml and 15.9 +/- 2.0 micrograms/dl, respectively) and the lowest at 2200 h (12.3 +/- 2.8 pg/ml and 4.6 +/- 1.0 micrograms/ml, respectively). These results suggest that the diurnal rhythm in ACTH and cortisol is under the regulation, at least in part, of the diurnal rhythm in CRF secretion.
Long-chained 1-mercapto-n-alkanes showed potent inhibitory effects on horse liver alcohol dehydrogenase (HLADH). The inhibitory effect of the thiols was enhanced by increasing the number of the alkyl carbon atoms up to 10-12 and steeply lowered by further increase in the carbon number. The HLADH activity was almost completely inhibited in competitive manner by an equivalent concentration of 1-mercapto-n-decane or -n-dodecane to that of the subunit of the dimeric zinc enzyme; inhibition constant Ki was 0.55 nM for the former. The present study strongly suggests that the thiols interact simultaneously with at least two sites of HLADH; the primary one could be the zinc atom in the active site of the enzyme, interacting with the sulfhydryl groups, and the other a hydrophobic binding site for the their alkyl carbons.
Enantiomers of 9,10-dihydrobenzo[a]pyrene 7,8-oxide (DBPO) were stereoselectivity conjugated with glutathione (GSH) specifically at benzylic carbon (C7) in normal Sprague--Dawley (SD) rat liver cytosol: (7R,8S)-(+)- greater than (7S,8R)-(-)-DBPOs. In contrast, in liver cytosol of SD rats bearing hepatic hyperplastic nodules induced with chemical carcinogens, (7S,8R)-(-)-DBPO was preferentially conjugated with GSH to (7R,8S)-(+)-DBPO. GSH S-transferases (GSTs) having sub-unit protein 4 were strongly suggested to play an important role in the preferential conjugation of (7R,8S)-(+)-DBPO in the normal rat liver cytosol, while the preferential conjugation of (7S,8R)-(-)-DBPO in the liver cytosol of the rat bearing hepatic hyperplastic nodules, was most likely to be attributable to GST 7-7, a characteristically induced protein in the hepatic hyperplastic nodules.
The carcinogen, 7,12-dihydroxymethylbenz[a]anthracene (DHBA), bound covalently through its 7-methylene carbon to calf thymus DNA via DHBA 7-sulphate, a regiospecifically formed, reactive metabolite, when incubated with rat liver cytosol in the presence of 3'-phosphoadenosine 5'-phosphosulphate (PAPS). The hydroxysteroid sulphotransferase inhibitor, dehydroepiandrosterone sulphate, strongly retarded the covalent binding of DHBA to DNA as well as the DHBA 7-sulphate formation from DHBA in the biological system, while pentachlorophenol and dichloronitrophenol showed little effect on these reactions. DHBA 7-sulphate was a good substrate for rat liver cytosolic glutathione (GSH) transferases, so that the PAPS-dependent covalent binding of DHBA to DNA could be markedly retarded in the presence of GSH with concomitant formation of a significant amount of the stable conjugate, S-(12-hydroxymethylbenz[a]anthracen-7-yl)methylglutathione. From DNA, incubated with DHBA in the presence of the hepatic cytosol and PAPS as well as with DHBA 7-sulphate alone, two purine base adducts were isolated after hydrolysis. The purine base adducts accounted for 70% of the total covalent binding of the carcinogen or its 7-sulphate to the nucleic acid and were identified with synthetic specimens as N6-(12-hydroxymethylbenz[a]anthracen-7-yl)-methyladenine and N2-12-hydroxymethylbenz[a]anthracen-7-yl)-methylguanine. The ratio of the adenine to guanine adducts was 1:2.5 with DNA, incubated with DHBA in the presence of hepatic cytosol and PAPS as well as with various concentrations of DHBA 7-sulphate.
Insulin-induced hypoglycemia is a potent stress stimulating ACTH release, but the factors responsible for this ACTH secretion are not known. In this study, several ACTH-stimulating factors, such as CRH, arginine vasopressin (AVP), epinephrine (E), norepinephrine (NE), and dopamine, in addition to ACTH, cortisol, and glucose, were simultaneously measured in plasma before and 15, 30, 60, 90, and 120 min after iv administration of 0.1 U/kg BW regular insulin to seven normal subjects. Insulin administration resulted in significant rises in the mean plasma ACTH level from 4.6 +/- 1.1 (+/- SEM) to 21.6 +/- 4.8 pmol/L at 30 min (P less than 0.01) and in plasma cortisol from 330 +/- 60 to 720 +/- 50 nmol/L at 60 min (P less than 0.01). These increases were preceded by a 41.0 +/- 1.9% (P less than 0.001) fall in blood glucose levels. The mean plasma CRH level rose significantly from 1.0 +/- 0.1 to 1.2 +/- 0.1 pmol/L (P less than 0.01) at 30 min and remained elevated until 120 min. In addition, concomitant and significant rises in plasma AVP levels (basal, 1.5 +/- 0.01; peak, 4.5 +/- 1.1 pmol/L at 30 min; P less than 0.01), E (basal, less than 50; peak, 640 +/- 130 pmol/L at 30 min; P less than 0.01), and NE (basal, 0.07 +/- 0.01; peak, 0.17 +/- 0.03 nmol/L at 60 min; P less than 0.05), but not dopamine, also occurred. These results suggest that multiple ACTH-releasing factors, such as CRH, AVP, E, and NE, are involved in ACTH secretion induced by insulin-induced hypoglycemia in man.
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Cholesterol epoxide hydrolase (CEHase) activities of mouse liver microsomes were completely inhibited by Emulgen 108 and Lubrol PX and approximately half by cholate, Triton WR-1339, and Tween 80 when preincubated with 0.1% of these detergents, while their xenobiotic epoxide hydrolase (XEHase) activities were markedly enhanced under the same preincubation conditions. The CEHase and XEHase activities were separately eluted from a gel column applied with mouse liver microsomes which were solubilized in a phosphate buffer containing cholate, glycerol, urea, dithiothreitol, and EDTA.