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Biomedical subjects

M Takaoka

Publications and source records attributed to M Takaoka.

At least 109 records · Page 6Linked to original sources

Phosphoramidon-sensitive endothelin converting enzyme in cultured vascular smooth muscle cells converts big endothelin-3 to endothelin-3.

Incubation of big endothelin-3 (big ET-3, 1-41) with the membrane fraction obtained from cultured vascular smooth muscle cells (VSMCs) resulted in time-dependent increases in immunoreactive-ET (IR-ET), which were suppressed by phosphoramidon. Analysis of the incubation mixture by reverse-phase high performance liquid chromatography (RP-HPLC) confirmed that the IR-ET was due to the mature ET-3 (1-21). ET-1 (1-21) generated during incubation of big ET-1 (1-39) with the membrane fraction was markedly suppressed by the addition of big ET-3 into the incubation mixture. When the cultured VSMCs were incubated with big ET-3, a conversion to the mature ET-3 was observed. This ET-3 generation from exogenously applied big ET-3 was also suppressed by phosphoramidon. We conclude that the phosphoramidon-sensitive ET converting enzyme in VSMCs converts big ET-1 and big ET-3 to their mature form.

Animals↗

Anastomosis of occipital artery to anterior inferior cerebellar artery with interposition of superficial temporal artery. Case report.

A 56-year-old man with vertebrobasilar insufficiency and associated findings including quadriparesis, dysarthria, cerebellar ataxia, nystagmus, and somnolence underwent left occipital artery (OA) to anterior inferior cerebellar artery (AICA) anastomosis with interposition of a superficial temporal artery (STA) graft. This procedure was chosen because cerebral angiograms demonstrated occlusion of the right vertebral artery (V3) and severe stenosis of the V4 segment of the left vertebral artery, with perfusion of the territory of the left posterior inferior cerebellar artery via the ipsilateral AICA, and because dissection of the OA is a relatively difficult and time-consuming procedure. Dissection of the STA, on the other hand, is much easier. Preoperative measurements of local cerebral blood flow in the vertebrobasilar circulation before and after intravenous administration of acetazolamide (500 mg) were obtained, and demonstrated low flow and hemodynamic compromise in the posterior circulation. The patient's hemodynamic and neurological status improved following surgery. In this report, we present a new and simplified method of OA-AICA anastomosis with interposition of STA graft.

Anastomosis, Surgical↗

Spontaneous globoid mineralization in the cerebellum of rats.

Cerebellar globoid mineralization in two rats was examined by light and electron microscopy, and by X-ray microanalysis. The mineralization was round to oval in shape; it varied in size and was positive for the periodic acid-Schiff and von Kossa reactions. Ultrastructurally, a concentric lamellar structure was prominent in moderately electron-dense depositions. Elemental analysis revealed the presence of large amounts of calcium and phosphorus, and small amounts of zinc, potassium and aluminum.

Animals↗

Tissue kallikrein in the rat pineal gland: an immunocytochemical study.

Tissue kallikrein in the rat pineal gland was immunocytochemically investigated with the aid of specific antiserum against rat urinary kallikrein. We also compared the tissue kallikrein immunoreactivity of the pineal gland with that of the submandibular gland and kidney, which have been well established as tissue kallikrein-synthesizing organs. The cytoplasm of pinealocytes from both the superficial and the deep portion of the gland exhibited specific immunolabeling for tissue kallikrein, but the immunoreaction was weaker than that observed in exocrine organs. Two types of tissue kallikrein-immunoreactive pinealocytes were distinguished; the first predominant type displayed moderate immunostaining, whereas a small number of cells, the second type, were so intensely labeled that their cytoplasmic processes were clearly outlined. The results of the present study suggest the existence of different types of pinealocytes and a potential physiological role of tissue kallikrein in the rat pineal gland.

Animals↗

Intramural rupture of the esophagus: a rare complication associated with nasobiliary catheter placement.

Intramural rupture of the esophagus developed after short-term nasobiliary catheter placement in an 87-year-old female with choledocholithiasis and suppurative cholangitis. Endoscopy revealed bleeding accompanied by circumferential disruption of the mucosa along the lower third of the esophagus. Withdrawal of the catheter and conservative treatment resulted in recovery of the lesion and relief of symptoms. This rare complication should be kept in mind during the placement of nasobiliary catheter.

Aged↗

Simultaneous ultrasonic monitoring of gallbladder emptying and gastric emptying after liquid test meal.

Gastric emptying and gallbladder emptying were measured simultaneously using simplified ultrasound (US) techniques after a liquid test meal in seven volunteers on two separate days. Sequential changes in cross-sectional areas of the gastric body and antrum and in gallbladder volume were represented as a monoexponential process after the test meal. There was a close correlation between the half emptying time (T1/2) of the stomach at the gastric body measured by US and that by simultaneous scintigraphic technique, but not between US at the antrum and scintigraphy. Gastric emptying measured at the gastric body was more reproducible than that at the gastric antrum. Sequential measurement of cross-sectional areas at the gastric body using ultrasound is simple and reliable for the assessment of gastric emptying after a liquid meal. US technique is promising for the evaluation of the relationship of gallbladder emptying to gastric emptying as a routine practice.

Adult↗

Endoscopic transpapillary biopsy for diagnosis of patients with pancreaticobiliary ductal strictures.

We used recently developed biopsy forceps to acquire transpapillary tissue in a consecutive series of 43 patients with pancreaticobiliary ductal strictures found during endoscopic retrograde cholangiopancreatographic examinations. There were 19 cholangiocarcinomas, 15 pancreatic carcinomas, five benign biliary, and four benign pancreatic ductal strictures. Tissue sampling from the strictures was successful in 41 patients (95.3%), without complications. All specimens were adequate for histologic evaluation. Eighty-one percent of the patients with carcinomas were diagnosed histologically by this technique. Sensitivity was 88% for cholangiocarcinoma and 71% for pancreatic carcinoma. There were no false-positive results. We conclude that transpapillary biopsy, being a simple, safe, and convenient method, should be applied as an initial diagnostic means during endoscopic retrograde cholangiopancreatography.

Adult↗

[Spike discharge detected by intra-arterial electroencephalography from intra-arterial guide wire in temporal lobe epilepsy].

The implantation of electrodes for intracranial electroencephalography (EEG) recording as presurgical evaluation of patients with intractable epilepsy is at present most important for planning epilepsy surgery. This method is most effective in temporal lobe epilepsy. We carried out intracranial EEG by means of insulated micro guide wire for endovascular surgery in two temporal lobe epilepsy cases, and spike discharges could be detected in lesional medial temporal lobe. Case 1 is a 29 year-old-male suffered from intractable complex partial seizure (CPS) for 18 years. He was diagnosed as left temporal lobe epilepsy and performed removal of amygdala, hippocampus, parahippocampal gyrus and fusiform gyrus. Case 2 is a 16 year-old-lady suffered from drug resistant CPS for 4 years. Under the diagnosis of right temporal lobe epilepsy, temporal lobectomy was performed. As the presurgical evaluation, under the implantation of subdural strip electrode in both cases, we carried intra-arterial EEG after angiography. Seeker Lite-10 guide wire was insulated with Tracker-10 unibody infusion catheter at sphenoidal portion of middle cerebral artery, and frequent interictal spike discharge was detected in lesional medial temporal lobes by two methods simultaneously.

Adolescent↗

[Multiple subpial transection after lesionectomy in an intractable epilepsy case].

A Sixty-one-year-old man was admitted to our hospital because of generalized convulsion. He had suffered from intractable epilepsy for 26 years. CT and MRI showed the right frontal cavernous angioma. On operation, intraoperative electrocorticography was performed after lesionectomy including surrounding glial scar and hemosiderin laden tissue. It showed epileptiform potentials in neighbor gyrus of the lesion. Because the removed sphere would be so broad, and we performed multiple subpial transection (MST). After MST, depression of background electrical activity and disappearance of spike discharge are seen. One and half year after operation, seizure was controlled by only phenobarbital administration.

Brain Neoplasms↗

Phosphoramidon-sensitive endothelin-converting enzyme in vascular endothelial cells converts big endothelin-1 and big endothelin-3 to their mature form.

Incubation of big endothelin-3 (big ET-3(1-41)) with the membrane fraction obtained from cultured endothelial cells (ECs) resulted in an increase in immunoreactive-ET (IR-ET). This increasing activity was markedly suppressed by phosphoramidon, which is known to inhibit the conversion of big ET-1(1-39) to ET-1(1-21). Reverse-phase HPLC of the incubation mixture of the membrane fraction with big ET-3 revealed one major IR-ET component corresponding to the elution position of synthetic ET-3(1-21). When the cultured ECs were incubated with big ET-3, a conversion to the mature ET-3, as well as an endogenous ET-1 generation, was observed. Both responses were markedly suppressed by phosphoramidon. By the gel filtration of 0.5% CHAPS-solubilized fraction of membrane pellets of ECs, the molecular mass of the proteinase which converts big ET-1 and big ET-3 to their mature form was estimated to be 300-350 kDa. Phosphoramidon almost completely abolished both converting activities of the proteinase. We conclude that the above type of phosphoramidon-sensitive metalloproteinase functions as an ET-converting enzyme to generate the mature form from big ET-1 and big ET-3 in ECs.

Animals↗

A simple method for measurement of phosphoramidon-sensitive endothelin converting enzyme activity.

We have developed a rapid and convenient assay for measurement of the action of endothelin (ET) converting enzyme (ECE) using the scintillation proximity assay (SPA) principle. On incubation of [125I]big ET-1 at 37 degrees C for 0.5-6 hr with an enzyme preparation, the reaction was terminated by the addition of an ET-1-specific antibody formulated in a buffer designed to shift the pH to alkaline. The antibody was allowed to come to equilibrium for 1 hr at room temperature and the amount of ET-1 produced, detected in a single step by the addition of protein A SPA beads. Using this assay, ECE activities of enzyme preparations obtained from porcine cultured endothelial cells and rat lung were clearly detected. These activities were inhibited by phosphoramidon in a concentration-dependent manner. The SPA based assay is homogeneous requiring no separation steps and takes a half day to complete. This method is therefore suitable for the high throughput screening of potential ECE inhibitors.

Animals↗

Species difference in susceptibility to phorbol myristate acetate-induced leukopenia and lung injury: rat vs. dog.

Phorbol myristate acetate (PMA) was administered intravenously in a single dose to rats (400 micrograms/kg) and in a single and repeated doses to dogs (40 micrograms/kg). Severe leukopenia was observed in both species. The leukopenia in rats was due to a decreased number of both lymphocytes and neutrophils while the leukopenia in dogs was mainly due to a decreased number of neutrophils. The rats recovered from leukopenia much faster than the dogs. The dog which received a single injection developed focal fibrosis in the lungs. Rats showed only slight localized hemorrhage in the lungs, although the rats received a ten-fold larger dose of PMA than the dogs. Lungs of dogs which received multiple injections revealed severe hemorrhagic lesions in most alveoli. Lung lesions induced by PMA are thought to be mediated by activated leukocytes. This suggests that the severity of lung lesion correlates with the degree and duration of neutropenia. In conclusion, intravenous administration of PMA caused lung damage in rats and dogs. However, rats show much less sensitivity to PMA than dogs, resulting from the different response of leukocytes to PMA.

Animals↗

Effects of endothelin-1 on antidiuresis and norepinephrine overflow induced by stimulation of renal nerves in anesthetized dogs.

The effects of endothelin-1 (ET-1) on renal function and norepinephrine (NE) overflow induced by renal nerve stimulation (RNS) were examined in anesthetized dogs, and comparisons were made with effects of Bay K 8644, a calcium channel agonist. RNS at a low frequency (0.5-2.0 Hz) produced significant decreases in urine flow and urinary excretion of sodium and increased NE secretion rates without influencing renal hemodynamics. RNS, at a high frequency of 2.5-5.0 Hz which diminishes renal hemodynamics, affected urine formation and NE secretion rate more potently than did low-frequency RNS. Intrarenal arterial infusion of ET-1 (1.0 ng/kg/min) decreased the baseline level of renal blood flow by 25% and that of urinary excretion of sodium by 54-69% but did not alter basal levels of NE secretion rate. During ET-1 infusion, low-frequency RNS-induced antidiuresis was observed to an extent similar to that seen without ET-1 infusion, whereas increase in NE secretion rate elicited by RNS was significantly inhibited by ET-1 infusion (45-65% of the values without ET-1 infusion). In addition, in the case of high-frequency RNS, ET-1 did not affect antidiuretic responses but did inhibit the increase in NE secretion rate by approximately 55%. In contrast, alterations in renal excretory responses and NE secretion rate elicited by RNS were not influenced by Bay K 8644 infusion (1.0 micrograms/kg/min), a dose that decreased renal blood flow to the same degree as did 1.0 ng/kg/min of ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Phosphoramidon inhibits the generation of endothelin-1 from exogenously applied big endothelin-1 in cultured vascular endothelial cells and smooth muscle cells.

When cultured porcine aortic endothelial cells (ECs) were incubated with porcine big endothelin-1 (bit ET-1(1-39)), there was a time-dependent increase in immunoreactive (IR)-ET in the culture supernatant, in addition to an endogenous IR-ET release fron the cells. Reverse-phase HPLC of the culture supernatant revealed one major IR-ET component corresponding to the elution position of synthetic ET-1, thereby indicating that the additional increase in IR-ET was due to the conversion of big ET-1 to mature ET-1(1-21). Phosphoramidon, a metalloproteinase inhibitor, strongly suppressed this increase in IR-ET as well as the endogenous IR-ET release. Cultured vascular smooth muscle cells (VSMCs) also released IR-ET. The apparent conversion of exogenously applied big ET-1 to ET-1 and its inhibition by phosphoramidon were observed using cultured VSMCs, although the enzyme inhibitor did not influence the basal secretion of IR-ET from VSMCs. These results suggest that both cultured ECs and VSMCs can generate ET-1 from exogenously applied big ET-1 via action of the same type of phosphoramidon-sensitive metalloproteinase, which is also involved in the endogenous ET-1 generation in ECs.

Animals↗