Chemical modification of glycyrrhetinic acid in relation to the biological activities.
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Biomedical subjects
Publications and source records attributed to S Shibata.
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To evaluate the role of the renal dopaminergic system on renal water-sodium metabolism patients with essential hypertension (EHT), urinary excretion of dopamine, urinary excretion of sodium (UNaV) and fractional excretion of sodium (FENa) were all investigated before and after the administration of dopamine (3 micrograms/kg/min, intravenous infusion for 60 minutes), dopamine antagonist, metoclopramide (8 mg/m2 BSA, intravenous injection) or mild sodium loading in both normotensive subjects and benign EHT. In the basal values, no significant difference in urinary excretion of free (u-fDA), conjugated (u-cDA) or total dopamine (u-tDA) was found between normotensives and hypertensives. However, low renin EHT showed a pronounced reduction in u-fDA compared with normotensis subject and (NT) normal renin EHT. In this study, a significant reduction of u-cDA and of u-tDA was also found in those patients with low renin essential hypertension. In the normotensive and essential hypertensive groups UNaV or FENa showed a positive correlation with u-fDA (measured simultaneously), but not with u-tDA or u-cDA. The regression line between u-fDA and UNaV or FENa in EHT was shifted towards a lower u-fDA level than in NT. UNaV and FENa were increased by dopamine infusion and were decreased by metoclopramide injection in both NT and EHT. Changes of UNaV and FENa following dopamine or metoclopramide, showed a negative correlation with u-fDA measured immediately before the administration of these drugs. The enhanced natriuretic response to infused dopamine and the attenuated antinatriuretic response to injected metoclopramide were significant in low renin EHT, when compared with NT or normal renin EHT patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Behavioral effects of zopiclone were investigated in mice and rats and compared with the data on diazepam, nitrazepam and flurazepam. The electroencephalographic effect of the drug was also examined in unanesthetized rabbits with chronic electrode implants and compared with that of diazepam. The present results indicate that zopiclone possesses pharmacological properties qualitatively similar to benzodiazepines, which are characterized by potent anticonflict and antiaggressive effects and much weaker anticonvulsant, muscle relaxant, ataxiogenic, sedative and anesthesia potentiating effects; the properties of this drug were compared with those of diazepam, nitrazepam and flurazepam. Zopiclone suppressed the EEG arousal responses and inhibited afterdischarges induced by electrical stimulation of the hippocampus and amygdala. The effects of zopiclone on EEG and afterdischarges were approximately 1/10 those of diazepam.
In isolated rabbit ear arteries incubated in a Ca2+-free medium with EGTA and nifedipine in the presence of norepinephrine, serotonin or histamine, an addition of Ca2+ induced a tonic contraction which is due to Ca2+ entry through receptor-operated Ca2+ channels (ROCs). Nitroglycerin (10(-4) M) significantly inhibited the ROCs-dependent contractions produced by serotonin or histamine, but failed to inhibit the ROCs-dependent contraction by norepinephrine. These results suggest the possible existence of two types of receptor-operated Ca2+ channels in rabbit ear artery.
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A glycopeptide comparable to human renal nephritogenic glycopeptide (nephritogenoside) of glomerular basement membrane (GBM) origin was isolated and purified from human placenta. Trophoblast basement membranes (TrBM) were isolated from placental terminal villi by ultrasonic disruption, and digested with trypsin and then with pronase. TrBM were then fractionated by zone electrophoresis, concanavalin A (Con A) affinity column chromatography and Bio-Gel P200 column chromatography. From 250 g (wet weight) of human placental terminal villi, we obtained a purified sample of 0.7 mg (dry weight) of glycopeptide. Ouchterlony gel diffusion demonstrated the existence of a common precipitin line between purified human placental glycopeptide and antiserum against human renal nephritogenic glycopeptide prepared from GBM. The sugar composition of this glycopeptide was rich in glucose (glucose, galactose and mannose were in the ratio of 1.00:0.30:0.33) and the amino acid composition of this glycopeptide contained no collagenous components. These results indicate that at least one of the nephritogenic substances common to the placenta and kidney is a glycoprotein rich in glucose and different from the collagenous component of the basement membrane.
Intracerebral cavernous hemangiomas are relatively easy to remove surgically, but extracerebral cavernous hemangiomas attached to the cavernous sinus are extremely difficult to treat. The authors report three cases of extracerebral cavernous hemangioma in the middle fossa that were treated with radiotherapy. The follow-up studies with serial computerized tomography (CT) scans during and after irradiation are described. In Case 1 radiotherapy after partial removal of the tumor decreased the tumor size on the contrast-enhanced CT scans, reduced its Hounsfield units on the nonenhanced CT scans, and facilitated later total tumor removal. In Case 2 the tumor responded to irradiation with approximately 3000 rads, showing significant reduction in size and Hounsfield units of the tumor. Subtotal removal was then possible. In Case 3 the tumor responded to irradiation, and the patient's vertigo improved after delivery of approximately 3000 rads. The CT scan showed significant reduction in the size and Hounsfield units of the tumor. No surgical intervention was deemed necessary. It is concluded that, in cases of extracerebral cavernous hemangioma with massive hemorrhage, irradiation with up to 3000 rads may be the treatment of choice. Radiation therapy offers an increased probability of total removal of the tumor and the possibility of eliminating surgery.
An injection of human renal tubular fraction, Fx1A, with Freund's complete adjuvant in rats induces Heymann nephritis (HN) with clinical and morphological features similar to rat Fx1A-induced HN. The present study was undertaken to characterize antibody specificities and the corresponding antigen involved in human Fx1A-induced HN. In sera of rats immunized with human Fx1A, not only anti-human Fx1A antibody but also antirat Fx1A antibody was detected by enzyme immunoassay. Eluted antibody from the glomeruli also showed both activities. In an inhibition study of enzyme immunoassay, binding of the eluted antibody to human Fx1A was inhibited by both human and rat Fx1A and also by partially purified gp330, but not by purified gp108. Furthermore, binding of the eluted antibody to rat Fx1A was inhibited by both rat and human Fx1A. On immunoblot, the eluted antibody mainly reacted with a 440 kD glycoprotein of human Fx1A which showed the same mobility as rat gp330. The antibody also reacted with a band of gp330 of rat Fx1A. These results indicate that the 440 kD glycoprotein in humans is a counterpart of rat gp330 and that the eluted antibody has dual specificities to both human 440 kD glycoprotein and rat gp330, suggesting that the cross-reactive antibody is responsible for human Fx1A-induced HN.
Effects of nicorandil on contractile responses to alpha 1-(methoxamine) and alpha 2-(clonidine and BHT-920) adrenoceptor agonists were examined in isolated rabbit aortae and femoral arteries. Nicorandil (10(-6) M and 10(-5) M) had greater inhibitory effects on contractile responses to clonidine (CL) and BHT than on responses to methoxamine (MO). In tissues treated with phenoxybenzamine, nicorandil (10(-5) M) inhibited residual responses to MO. The relationship between maximum contraction and percent-receptor occupancy was nonlinear for MO, but was near linear for CL and BHT. Prazosin had much greater inhibitory effect on responses to MO and CL than did yohimbine. Nicorandil only slightly inhibited the contractile response of both aorta and femoral arteries to K+ or excess Ca2+, while nifedipine (10(-6) and 10(-5) M) nearly abolished it. In a Ca2+-free medium containing EGTA, nicorandil (10(-7)-10(-5) M) inhibited residual responses of the aorta to BHT, CL, and MO in a concentration-dependent manner. The inhibitory effect of nicorandil was much greater on responses to BHT and CL than to MO. In addition, nicorandil (10(-7)-10(-5) M) inhibited the response of the aorta to Ca2+ (2 mM) added to a Ca2+-free medium containing EGTA, nifedipine (10(-6) M), and an agonist (BHT, CL, or MO). Furthermore, in aortae pretreated with phenoxybenzamine, nicorandil nearly abolished the residual response to MO in a Ca2+-free medium containing EGTA.(ABSTRACT TRUNCATED AT 250 WORDS)
Previously, we have shown that okadaic acid (OA), isolated from black sponge (Halichondria okadai) causes contraction even in the absence of Ca++ in the saponin-permealized taenia isolated from guinea pig cecum. In the present study, mechanism of action of OA was examined using native actomyosin extracted from chicken gizzard smooth muscle. In the absence of Ca++, OA (0.1-1 microM) induced superprecipitation and increased the Mg++-adenosine triphosphatase activity. The OA-induced superprecipitation was enhanced by Ca++ at a concentration (greater than 0.1 microM) which did not activate the calmodulin-dependent myosin light chain (MLC) kinase. The effect of OA was not affected by the calmodulin inhibitor, trifluoperazine, at a concentration (100 microM) needed to inhibit the Ca++-induced response, but was inhibited markedly by the nonselective kinase inhibitors, amiloride (1 mM) and K-252a (5 microM). The OA-induced superprecipitation in the absence of Ca++ was accompanied by phosphorylation of the 20 K dalton MLC, which also was enhanced by low concentration of Ca++ (greater than 0.1 microM). OA did not change the phosphatase activity which dephosphorylates the phosphorylated MLC. An activator of Ca++- and phospholipid-dependent protein kinase, 12-O-tetradecanoylphorbol 13-acetate (1 microM), did not modulate superprecipitation or phosphorylation of MLC in the presence and absence of OA. Furthermore, inhibitors of Ca++ and phospholipid-dependent protein kinase, 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine dihydrochloride (400 microM) and polymyxin B (100 micrograms/ml), affected neither superprecipitation nor phosphorylation of MLC induced by OA. With a reconstituted system containing purified myosin and MLC kinase, OA induced only slight phosphorylation of MLC.(ABSTRACT TRUNCATED AT 250 WORDS)
Our previous paper showed that the glycoprotein of Mr 108,000 (gp108) is one of the major components of rat renal tubular brush border antigens and that an injection of anti-gp108 antiserum in rats induces passive Heymann nephritis with acute and severe proteinuria. In this study, gp108 was identified as a monomer of dipeptidyl peptidase IV (DPP IV). The anti-gp108 antibody was shown to immunoprecipitate DPP IV from Triton-extract of renal tubular membrane fractions. DPP IV was co-purified with gp108 from the Triton-extract by columns of DEAE-cellulose and Bio-gel A-1.5 m. The ratio of DPP IV activity and gp108 content was nearly constant throughout the purification steps. The final purified gp108 showed a high specific activity of DPP IV, comparable to that reported for purified rat DPP IV. These results indicate that gp108 is a monomer of DPP IV.
In rabbit aorta, pretreatment with KT-362 (KT; 10(-6) and 10(-5) M) inhibited contractile responses to norepinephrine (NE; 3 X 10(-9)-10(-5) M) and methoxamine (10(-7)-10(-4) M) but failed to affect responses to potassium (10-70 mM). KT (10(-5) M) partially inhibited Ca++-induced contractions in K+-depolarized aorta pre-equilibrated in a Ca++-free medium. After incubation of tissues for 30 min in a Ca++-free medium containing EGTA (0.2 mM), residual responses to NE and methoxamine were inhibited by KT (10(-6)-10(-4) M) and nitroglycerin (10(-5) M), but not by nifedipine, verapamil or diltiazem (all 10(-5) M). The inhibitory action of a combined treatment with KT and nitroglycerin (both 10(-5) M) on the residual response to NE was also much greater than that of either agent alone. In a Ca++-free medium, the residual caffeine-induced contraction of rabbit iliac artery was inhibited by KT (10(-5)-10(-4) M) but not by nifedipine (10(-5) M). The inhibitory action of KT on the residual responses to methoxamine and caffeine in a Ca+-free medium was much greater than that of nitroglycerin. In a Ca++-free medium with low EGTA (0.01 mM), D600 (10(-5) M) and NE (3 X 10(-7) M), the addition of Ca++ (2 mM) resulted in a tonic contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
We recently reported that an injection of antibody raised against renal brush border glycoprotein, gp108, in rats induced passive Heymann nephritis with acute and severe proteinuria. In this study, the distribution of gp108 in various rat tissues was investigated. On enzyme immunoassay, anti-gp108 antibody reacted to extracts of small intestine, lung, spleen, thymus, liver, epididymis, stomach, pancreas and heart. It also reacted to sera and extracts of peripheral blood cells, especially lymphocytes. These antigens, which are cross-reactive to kidney gp108 have similar biochemical properties: a molecular weight of about 108,000 and an isoelectric point of 4.8-5.4. These results show that immunologically and biochemically related antigens to renal glycoprotein, gp108, are present in various rat tissues.
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Facial nerve schwannoma is rare. Since the first description by Schmid, about 150 cases have been reported mainly in the otological field. The authors recently had a case of facial nerve schwannoma with a marked capsular calcification, extending into the middle cranial fossa. A 63-year-old man was admitted to our hospital on June 20, 1986. About 44 years prior to the admission, he noted facial weakness of the right side which gradually progressed. Neurological examination on admission revealed complete right facial paralysis of the peripheral type with loss of taste, right hearing loss, diminution of lacrimal secretion and no reaction to caloric stimulation. Stenvers' view and tomogram of the right temporal bone showed destruction of petrous ridge. CT scan demonstrated bony destruction of the right petrous pyramid and high dense mass lesion, extending into the middle cranial fossa. Peritumoral and intratumoral calcifications, characteristics of facial nerve schwannoma were also noted. Right external carotid angiography demonstrated the tumor was fed by petrous branch of the right middle meningeal artery. On July 11, 1986 right temporal craniotomy and extradural approach to the floor of the petrous portion of the middle cranial fossa were performed. There was an extradural mass which extended to the middle cranial fossa through the destroyed pyramis. The tumor appeared to originate from the geniculate ganglion of the facial nerve and invaded the inner and middle ear which were almost completely removed. Operative specimen demonstrated that the tumor was a schwannoma. Postoperative hearing test and facial nerve function showed no changes as compared with preoperative findings. Similar case reports with CT findings were reviewed.