Biomedical subjects

M Takaoka

Publications and source records attributed to M Takaoka.

At least 91 records · Page 5Linked to original sources

PubMed1994

Differences in potency of big endothelin-1-induced pressor action in rat isolated perfused mesenteric artery, hindquarter and lung.

We compared the pressor response to endothelin-1 (ET-1) with that of big endothelin-1 (big ET-1) in mesenteric arteries, hindquarters and lungs of rats. In these three preparations, both peptides caused a concentration-dependent increase in the perfusion pressure. The ratio of big ET-1 concentration to ET-1 concentration needed for causing the same pressor action is different between organs; i.e., a mesentery >> a hindquarter > or = a lung. Exposure to phosphoramidon, a metalloproteinase inhibitor, significantly suppressed the pressor response to big ET-1, in a similar fashion. This suppression is likely to be due to the inhibition of phosphoramidon-sensitive endothelin converting enzyme, since the inhibitor does not suppress an action of ET-1. Apparently there is a difference in potency for phosphoramidon-sensitive vasoconstriction of big ET-1 between organs and presumably regional differences in the functional phosphoramidon-sensitive conversion of big ET-1 in vasculatures.

Animals↗

PubMed1994

Intrarenal conversion of big endothelin-1 to endothelin-1 in the rat.

Intravenous (i.v.) or intrarenal arterial (i.r.a.) injection of big endothelin-1 (big ET-1) (1.6 nmol/kg) in anesthetized rats produced a significant increase in mean arterial pressure (MAP), a decrease in renal blood flow (RBF) and an increase in renal vascular resistance (RVR). Although the pressor responses to big ET-1 of i.v. and i.r.a. injection were not significantly different, i.r.a. injection of big ET-1 caused a significantly greater reduction in RBF than that seen with i.v. injection of big ET-1. The effects of i.r.a. injection of the peptide on MAP and RBF were markedly suppressed by phosphoramidon. Big ET-1 caused dose-dependent pressor effects in isolated perfused rat kidney and these pressor effects were significantly suppressed by phosphoramidon. Thus, renal vasculature possesses a phosphoramidon-sensitive endothelin converting enzyme, which may play an important role for the renal hemodynamic regulation.

Animals↗

PubMed1994

Successful intra-arterial fibrinolysis of the anterior choroidal artery in the acute stage of internal carotid artery occlusion: case report.

A 27-year-old man was admitted to our institution with the sudden development of right hemiparesis and dysarthria beginning an hour after the onset of symptoms on August 9, 1992. The patient was found on admission to have right hemiparesis (2/5), hemihypesthesia, hemianopia, dysarthria; he had transient atrial fibrillation. No abnormalities were detected on computed tomography (CT) scans, and cerebral blood flow studies undertaken following conventional CT scans revealed no low flow regions in the left cerebral hemisphere. But cerebral angiography disclosed an occlusion of the left internal carotid artery with well-developed cross-circulation via the anterior communicating artery and embolus lodged at the level of the anterior choroidal artery. Superselective fibrinolysis using Tracker-18 and 420,000 units of urokinase resulting in complete recanalization of the left anterior choroidal artery without distal migration of the embolus. Immediately after the procedure, his neurologic disturbance underwent complete resolution. In summary, fibrinolysis could be performed but limited to anterior choroidal artery in a case with an occlusion of the internal carotid artery with well-developed cross-flow via the anterior communicating artery; the patient's neurologic condition may deteriorate suddenly if fibrinolysis is incomplete and the embolus migrates to the internal carotid artery.

Acute Disease↗

PubMed1994

Involvement of transforming growth factor-beta 1 for platelets-induced stimulation of endothelin-1 production.

1. Possible mechanisms by which platelets stimulate the production of endothelin-1 (ET-1) in vascular endothelial cells (EC) were investigated. 2. A supernatant of platelets stimulated the expression of prepro ET-1 mRNA, followed by an increased secretion of ET-1 from cultured EC. These responses were markedly enhanced by pretreatment of the platelets with thrombin, at a concentration which did not influence the ET-1 production in EC. A platelet suspension, separated from cultured EC by a permeable nylon membrane, also markedly stimulated the ET-1 secretion from EC. 3. Endothelin-1 production enhanced by the platelet supernatant, with or without thrombin pretreatment, correlated with the active transforming growth factor-beta 1 (TGF-beta 1) concentrations in the supernatant. The supernatant-induced increase in ET-1 secretion from the EC was markedly suppressed by TGF-beta 1 neutralizing antibody. 4. We tentatively conclude that platelets stimulate the endothelial ET-1 production by releasing a bioactive diffusible substance, mainly TGF-beta 1.

Animals↗

PubMed1994

Conversion of big ET-1 in the rat lung: role of phosphoramidon-sensitive endothelin-1-converting enzyme.

We examined conversion of Big endothelin-1 (ET-1) to mature ET-1 and pressor action during perfusion of the isolated perfused rat lung with Big ET-1. Big ET-1 caused a concentration-related increase in perfusion pressure and the pressor molar potency of the peptide was fivefold less than that of ET-1. Pressor responses to Big ET-1 were accompanied by an increase in immunoreactive-ET (IR-ET) levels in the perfusate and in the lung tissues. Pretreatment with phosphoramidon (10(-4) M), a metalloproteinase inhibitor, markedly suppressed the pressor action and increment in IR-ET in the tissues. Unexpectedly, the amount of IR-ET in the perfusate during perfusion of Big ET-1 was not influenced by phosphoramidon treatment. On the other hand, chymostatin, an inhibitor of chymotrypsin-like enzymes, effectively suppressed IR-ET levels in the perfusate; however, this enzyme inhibitor was without effect on the pressor action of Big ET-1 or on the increase in IR-ET levels in lung tissues. We tentatively conclude that the phosphoramidon-sensitive conversion of Big ET-T to ET-1 is linked to the pressor action of Big ET-1 in the isolated perfused rat lung. In addition, it seems likely that chymostatin-sensitive conversion of Big ET-1 to ET-1 does not play a major role in the conversion of the precursor to the mature form. We propose that IR-ET present in the tissues rather than that in the perfusate is a better indicator of the functional conversion of Big ET-1 in the rat lung.

Animals↗

PubMed1994

Phosphoramidon-sensitive conversion of big endothelin-1 and degradation of endothelin-1 in rat kidney.

We investigated the intrarenal conversion of big endothelin-1 (ET-1) to ET-1 in the isolated perfused rat kidney. Big ET-1 caused a concentration-dependent increase in perfusion pressure, and the pressor molar potency of the peptide was 50-fold less than that of ET-1. The big ET-1 (2 x 10(-8) mol/L)-induced pressor action was accompanied by increases in immunoreactive endothelin levels in both the perfusate and renal tissues. Phosphoramidon (10(-4) mol/L), a metalloproteinase inhibitor, significantly suppressed the big ET-1-induced pressor action and the accumulation of immunoreactive endothelin in renal tissues. On the other hand, phosphoramidon slightly but significantly sustained the ET-1-induced pressor effect. The effect of kelatorphan (10(-4) mol/L), a specific inhibitor of neutral endopeptidase 24.11, on the ET-1-induced pressor effect was the same as that seen with phosphoramidon. When ET-1 was exogenously added to the perfusate, phosphoramidon or kelatorphan significantly increased the immunoreactive endothelin levels in renal tissues after perfusion, without affecting the disappearance rate of immunoreactive endothelin from the perfusate. Therefore, the phosphoramidon-sensitive ET-1-converting enzyme in the kidney seems to contribute to the functional local conversion of big ET-1 to ET-1, and neutral endopeptidase 24.11 may be responsible for the proteolytic degradation of ET-1 in the kidney. In addition, immunoreactive endothelin levels in renal tissues but not in the perfusate can account for the functional conversion of big ET-1 to ET-1 and for the local proteolytic degradation of ET-1 in the kidney.

Animals↗

PubMed1994

Vascular mineralization in the monkey brain.

Mineralization of various degrees was found in the brains of 79 (59%) of 134 cynomolgus monkeys (Macaca fascicularis). There was no age dependency in the incidence or severity, nor were there any abnormalities in growth, weight gain, or neurologic signs, although a slight sex difference was observed. The lesions, which were basophilic and intensely positive for periodic acid-Schiff or von Kossa stain, occurred in the vascular walls of the globus pallidus in two types: globoid bodies with prominent concentric lamellar structures in and around the arteriolar and venular wall (type A) and fine granules in the media of small or medium-sized arteries (type B). Electron microscopic examination revealed dense deposits in the degenerated media of small or medium-sized arteries or the thickened walls of the arterioles. X-ray microanalysis demonstrated the presence of calcium, phosphorus, iron, zinc, magnesium, and aluminum.

Animals↗

PubMed1994

Comparative study of goitrogenic actions of 3-substituted 1, 2, 4-triazoles in rats.

Antithyroid actions of 3-amino-1, 2, 4-triazole (ATZ), 3-mercapto-1, 2, 4-triazole (MTZ) and 3-nitro-1, 2, 4-triazole (NTZ), which are substituents on the 3-position of 1, 2, 4-triazole (TZ), and those of the parental compound, were compared in rats. After administration of either ATZ, MTZ, or NTZ, the thyroids of rats were enlarged with decreasing of colloid content and a proliferation of the follicular epithelia. The serum concentration of 3, 5, 3'-triiodothyronine and thyroxine decreased, while that of thyroid-stimulating hormone increased. ATZ, MTZ, and NTZ inhibited thyroid peroxidase activity both in vivo and in vitro. These antithyroid actions were the most remarkable in case of MTZ and were the least in case of NTZ. TZ had no effect on the thyroid function in vivo and in vitro. The results of Lineweaver-Burk analysis on the effect to lactoperoxidase activity indicated that ATZ, MTZ, and NTZ showed competitive inhibition. These results suggest that both MTZ and NTZ have goitrogenic effects on the thyroid through antiperoxidase action, such as ATZ. Thus, the 3rd carbon position of TZ is thought to be important for induction of goiter in rats. A comparison of the relationship between substituent on the 3-position of TZ and antithyroid activity shows that a mercapto moiety has more potent antithyroid action than an amino and a nitro moiety. It is concluded that the differences in antithyroid activity of TZ derivatives depend on the potency of the substituents.

Animals↗

PubMed1994

A case of intracytoplasmic edema of follicular epithelial cells in rat thyroid.

Hydropic change of follicular epithelial cells in the thyroid was observed in a female Fischer 344 rat. Microscopically follicular epithelial cells were characterized by edematous swelling with weakly eosinophilic and homogeneous cytoplasm. The cytoplasm was negative for periodic acid-Schiff reaction, and thyroxine- and thyroglobulin-immunohistochemical reactions. Electron-microscopically, a small amount of amorphous substance was noted in remarkably dilated rough-surfaced endoplasmic reticulum (r-ER), and slight regressive changes of cytoplasmic organella were also observed. These morphological changes may indicate that focal intracytoplasmic edema was occurred in r-ER, and that the change belonged to hydropic degeneration of the thyroid follicular cells in the thyroid.

Animals↗

PubMed1994

Effect of single and multiple administrations of cisapride on postprandial gallbladder emptying in healthy humans.

Effects of a clinical dose of the prokinetic drug, cisapride, on postprandial gallbladder emptying were evaluated in 8 healthy normal volunteers. Gallbladder and gastric emptying after a liquid test meal were simultaneously measured by ultrasonography. Compared with placebo, a single oral dose of cisapride (5 mg) accelerated gastric emptying, but not gallbladder contraction. Cisapride enhanced gallbladder refilling. The same individuals took oral cisapride (15 mg TID) for 14 days, and were reassessed on the following day after oral 5 mg of cisapride. Fasting gallbladder volume was significantly increased. Although gallbladder contractility was not affected, the residual volume was significantly large. Gastric emptying rate returned to the control value. Fasting and post-test meal plasma CCK levels were not significantly attenuated by either single or multiple administration of cisapride. These results suggest that a clinical dose of cisapride may attenuate gallbladder motor function via mechanisms other than direct neural stimulation of the gallbladder.

Administration, Oral↗

PubMed1994

Endoscopic endoprosthesis for large stones in the common bile duct.

Endoscopic biliary endoprosthesis was performed for 34 high-risk patients with common bile duct stones too large to be extracted by conventional endoscopic means. Bile duct drainage was established in all the patients without complications. Late complications developed in four patients and included cholangitis (three) and biliary pain (one). Twenty-five patients underwent a second endoscopic retrograde cholangiopancreatography between 4 and 30 months (mean, 15.1) during follow-up. Stone fragmentation was obtained in 76% (19/25) of the patients. Ten patients had complete stone clearance, and nine patients had disintegrated stones which could be readily removed endoscopically. The remaining nine patients were followed up with endoprostheses in situ for four to 60 months (mean, 24.8) without any symptoms. These results suggest that endoscopic endoprosthesis for difficult common bile duct stones is an effective method to clear the duct in selected cases, as well as an important definitive treatment in high-risk patients.

Aged↗

PubMed1994

Pituitary adenoma invading the skull base--a strategy for skull base surgery.

A strategy for surgical management, including the approach and preoperative evaluation, of pituitary adenoma invading the skull base is described. Preoperative evaluation requires a balloon occlusion test of the internal carotid artery (ICA) to determine tolerance to occlusion. Failure to tolerate occlusion indicates administration of brain protective agents and/or a bypass procedure before tumor removal. The transsphenoidal, pterional, orbitofrontomalar, and infratemporal fossa approaches are all suitable for various tumor locations. A combined orbitofrontomalar and extended frontal approach allows removal of tumor with extensive invasion and is suitable for bypass procedures. Preoperative evaluation of ICA occlusion can prevent development of hemodynamic stroke. We treated five patients with pituitary adenoma invading the skull base, including two primary and three recurrent cases. All symptoms improved, but temporary oculomotor nerve disturbance occurred in three patients and anosmia in one. Reoperations for recurrent pituitary adenomas were effective in reversing the symptoms. No hemodynamic stroke was seen postoperatively. These tumors, except for drug-responsive cases, are indicated for skull base surgery.

Adenoma↗

PubMed1994

The effects of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, on norepinephrine overflow and antidiuresis induced by stimulation of renal nerves in anesthetized dogs.

We examined the involvement of endogenous nitric oxide (NO) in noradrenergic neurotransmission and renal function in anesthetized dogs, by using NG-nitro-L-arginine (NOARG), a NO synthase inhibitor. Renal nerve stimulation (RNS) produced the frequency-dependent increase in the rate of norepinephrine secretion. The low frequency RNS (0.5-2.0 Hz) decreased urine flow and urinary excretion of sodium, without affecting renal hemodynamics. High frequency RNS (2.5-5.0 Hz) caused a more potent antidiuresis and renal vasoconstriction that resulted in reductions in renal blood flow and glomerular filtration rate. Intrarenal arterial infusion of NOARG, at a dose (10 micrograms/kg/min) which had no effect on renal hemodynamics, significantly enhanced the RNS-induced reductions of urine formation and renal vasoconstriction and increments in norepinephrine secretion rate. Qualitatively similar results were observed with a higher dose of NOARG (40 micrograms/kg/min), although this dose did decrease basal levels of renal blood flow and urine flow. Enhancement of NOARG on RNS-induced actions was abolished by the simultaneous administration of L-arginine. Endogenous NO probably has a role as inhibitory modulator of renal noradrenergic neurotransmission.

Amino Acid Oxidoreductases↗

PubMed1994

Intestinal absorption of serrapeptase (TSP) in rats.

A sensitive sandwich enzyme immunoassay (e.i.a.) for serrapeptase (TSP), an orally available anti-inflammatory proteinase, was established using affinity-purified anti-TSP rabbit IgG and its Fab' fragment conjugated with horseradish peroxidase as the first and the second antibodies respectively. TSP in the plasma was determined by the e.i.a. after its oral administration (100 mg/kg) to rats. The peak concentration was observed between 30 min and 2 h after administration. TSP in the plasma samples was trapped on a microtitre plate coated with the affinity-purified anti-TSP rabbit IgG, and the hydrolysis of a synthetic fluorogenic substrate, butoxycarbonyl-Glu(benzyloxy)-Ala-Arg-4-methylcoumaryl-7-amide, by the trapped TSP was fluorometrically measured (proteinase assay). The values obtained by the e.i.a. and those obtained by the proteinase assay correlated well for various plasma samples. These results indicate that orally administered TSP was absorbed from the intestinal tract and transferred into the circulation in an enzymically active form.

Administration, Oral↗

PubMed1994

Platelets-induced stimulation of endothelin-1 production and inhibition by phosphoramidon.

The effects of platelets on endothelin-1 (ET-1) production were examined by using cultured bovine pulmonary artery endothelial cells (ECs). Platelets (6 x 10(6) to 2 x 10(9) platelets/ml) prepared from rat peripheral arterial blood markedly stimulated immunoreactive (IR)-ET release from ECs into the culture medium, in a time-and platelet number-dependent manner. High-performance liquid chromatography analysis of the culture supernatant following exposure to platelets revealed one major IR-ET component corresponding to the elution position of synthetic ET-1. Northern blot analysis showed that platelets enhanced prepro ET-1 mRNA expression in the ECs. Increased IR-ET release was observed with the supernatant obtained after incubation of platelets, and this increment was significantly inhibited by transforming growth factor-beta 1 neutralizing antibody. Phosphoramidon, an ET converting enzyme inhibitor, significantly decreased the amount of IR-ET accumulating in the culture medium of ECs, incubated with or without platelets, and the decreasing effect of phosphoramidon in the presence of platelets was greater than that in their absence. A similar effectiveness of phosphoramidon was seen when transforming growth factor-beta 1 was used instead of platelets. Thus, platelets appear to stimulate the endothelial production of ET-1 in vitro, probably through a release of transforming growth factor-beta 1. We also suggest that the inhibition of ET converting enzyme by phosphoramidon is more effective in the augmented condition of ET-1 production than in the basal condition.

Animals↗

PubMed1993

Endothelium-independent pressor effect of big endothelin-1 and its inhibition by phosphoramidon in rat mesenteric artery.

We asked whether or not the endothelium plays a functional role in the conversion of big endothelin-1 to endothelin-1 in the perfused rat mesenteric artery. In endothelium-denuded preparations, big endothelin-1 produced a much more potent pressor effect than in intact preparations. Phosphoramidon suppressed the big endothelin-1-induced pressor action without affecting the action of endothelin-1, irrespective of the presence or absence of the endothelium. The amounts of immunoreactive-endothelin in the perfusate during perfusion of endothelium-denuded preparations with big endothelin-1 were extremely low compared with those observed in intact preparations and were not significantly suppressed by the metalloproteinase inhibitor, phosphoramidon, in contrast to the case with intact preparations. When synthetic endothelin-1 was perfused in the endothelium-denuded mesentery, the peptide disappeared from the perfusate more rapidly than with intact preparations, suggesting that endothelin-1 generated from big endothelin-1 is effectively trapped by vascular smooth muscle cells in the endothelium-denuded preparation. Our results suggest that the endothelium is not essential for the conversion of big endothelin-1 to endothelin-1, in rat mesenteric artery.

Animals↗

PubMed1993

Big endothelin-3-induced hypertension and its inhibition by phosphoramidon in anaesthetized rats.

Intravenous injection of big endothelin-3 (big ET-3, 1-41 amide) at 3 nmol/kg to ganglion-blocked anaesthetized rats produced a long-lasting hypertensive action, but the action was less potent than that seen with the same dose of ET-3-(1-21). The pressor effect induced by big ET-3 was markedly attenuated by pretreatment with phosphoramidon, 5 mg/kg i.v., a dose which had no effect on the hypertensive action induced by ET-3. These results strongly suggest that big ET-3 is converted to mature ET-3 by a phosphoramidon-sensitive metalloproteinase in vivo, in a manner similar to the conversion of big ET-1 to ET-1.

Anesthesia↗

PubMed1993

Anatomical variation of pancreatobiliary ducts in biliary stone diseases.

Endoscopic retrograde cholangiopancreatography examinations were prospectively analyzed to determine whether anatomical variations of ductal systems have a role in the pathogenesis of cholecystolithiasis and choledocholithiasis. Included were 140 normal examinations (control group), 102 patients with cholecystolithiasis, and 68 patients with choledocholithiasis (primary stones in the common bile duct). Low entry of the cystic duct was observed frequently in patients with cholecystolithiasis (15.7% vs. 2.1% in control, p < 0.01). No preferential type of course of the cystic duct was observed in patients with cholecystolithiasis and choledocholithiasis. Separate openings of the bile and pancreatic ducts were significantly prevalent in patients with choledocholithiasis (53.5% vs. 30.6% in control, p < 0.01). Common channel was significantly short in patients with cholecystolithiasis. Incidence of juxtapapillary duodenal diverticula was significant in patients with choledocholithiasis. These observations suggest that some of the pancreatobiliary ductal anatomy may be closely implicated in the development of gallstone diseases.

Aged↗