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Biomedical subjects

K Goto

Publications and source records attributed to K Goto.

At least 667 records · Page 37Linked to original sources

Role of endothelin in mechanisms of local blood pressure control.

A potent endothelium-derived vasoconstrictive peptide, endothelin (ET), is processed from a precursor, big endothelin, by an unknown converting enzyme. It stimulates calcium channels, phospholipase C and phospholipase A2 in smooth muscle cells through activation of the receptor specific for ET. The intracellular free calcium ion concentration is increased by ET, inducing vasoconstriction. The response to ET varies according to the type of blood vessel. Mesenteric small arteries and arterioles are sensitive to ET. It is likely that various factors, including adrenaline, angiotensin II and arginine vasopressin, induce synthesis and release of ET from the endothelium. A balance among ET, endothelium-derived relaxing factor (EDRF) and atrial natriuretic peptide (ANP) may control vascular tone and regulate peripheral blood flow.

Amino Acid Sequence↗

[Anticoagulant therapy in obstetrical disorders].

Three kinds of anticoagulant therapy for obstetrical DIC were studied. 1. Antithrombin-III (AT) or gabexate mesilate for acute DIC, mainly for abruptio placentae. 2. Heparin or heparin-AT combination therapy for toxemia pregnancy. 3. Low molecular weight heparin (LMWH) for fetus of intrauterine growth retardation (IUGR). The results obtained were as follows, 1. a) Platelet count, and fibrinogen were significantly increased in AT therapy group compared with gabexate mesilate group. b) In clinical manifestation, renal failure and hemorrhagic diathesis were improved especially in AT group. 2. In heparin-AT group, high systolic blood pressure was improved during administration of AT, the high level of thrombin antithrombin complex was also found in these period. 3. a) The improvement of the gain of estimated fetal body weight was found after administration of LMWH. b) Redistribution of blood flow in one case of severe IUGR was observed during administration of LMWH.

Antithrombin III↗

[Clinical evaluation of serum S100ao protein in patients with urogenital diseases and healthy volunteers].

We investigated the clinical significance of the serum S100ao protein in patients with urogenital diseases. The serum levels of S100ao protein were measured in 179 patients with urogenital diseases and 180 healthy volunteers. The mean value of S100ao protein in serum from healthy volunteers was 203 +/- 107 pg/ml (Mean +/- SD). Therefore, the cut-off level was set to 524 pg/ml (Mean +/- 3SD). The levels of S100ao protein in serum were significantly higher in men than in women (P less than 0.05). The levels of S100ao protein in serum were significantly high in the patients in their fifties and sixties compared with the other patients (P less than 0.01). When serum levels exceeding the cut-off level were considered to be positive, the percentages of positivity in each disease were as follows: renal cell carcinoma; 38.7%, bladder tumor; 9.1%, prostatic carcinoma; 12.5%, testicular tumor; 0%, benign prostatic hypertrophy; 7.4%, urolithiasis; 7.1% and chronic renal failure; 100%. The levels of S100ao protein in serum were significantly correlated with those of BUN, serum creatinine and endogenous creatinine clearance, respectively. S100ao protein in serum was increased immediately after operation and returned to the normal range within one to two weeks after operation. As described above, the level of S100ao protein in serum was affected by renal function, operative procedures and age. However, the positive rate of S100ao protein was so high in patients with renal cell carcinoma that serum S100ao protein might be a valuable tumor marker in those patients.

Adult↗

[Capsular pseudobulbar mutism in a patient of lacunar state].

A patient of mutism with pseudobulbar palsy and frontal lobe syndrome resulting from lacunar state was reported. The patient, a 64-year-old man, was admitted to Gifu University Hospital because of a decrease in spontaneous activity, lack of volition and anorexia. The CT scan, performed on July 29, 1987, demonstrated lacune in the right internal capsule (IC), periventricular lucency especially around the anterior horn of lateral ventricles, and ventricular dilatation. He was transferred to a medical ward because of repeated aspiration pneumonia. Neurological examination revealed mutism, pseudobulbar palsy, and frontal lobe signs. The CT scan, performed on March 30 1988, demonstrated the newly developed lacune in the left IC. The MRI also showed two coinciding lacunes, one in the genu of the right IC and the other in the anterior limb of the left IC. The SPECT with 123I iodoamphetamine showed decreased blood supply predominantly to the frontal lobes. A mechanism by which the mutism occurs is discussed from two points of view, pseudobulbar palsy and frontal lobe syndrome. He developed initially frontal lobe syndrome in which paucity of spontaneous speech was noted. The CT scan at that time demonstrated lacune in the right IC. About eight months later when he became mute, the CT scan showed lacunes in bilateral ICs without any other low density areas in frontal language areas such as Broca's area, subcortical area and supplementary motor area. As the MRI showed that the right lacune was in the genu but the left lacune was in the anterior limb of IC, the left cortico-bulbar tract was thought to be not directly involved. The SPECT showed decreased blood supply predominantly to the frontal lobes. Although dysphagia improved, mutism did not improve at all. Therefore it is postulated that both pseudobulbar palsy and frontal lobe dysfunction might play a role in producing the mutism of this patient.

Akinetic Mutism↗

[Fournier's gangrene: a case report].

A 40-year-old male was admitted complaining of high grade fever, pain, redness and swelling of the right scrotum, right perineum and right flank region. He had no apparent history of previous infection or diabetes mellitus. At the time of admission, the scrotum was partly necrotic with repulsive feculent pus discharge and there was crepitus on palpation of involved areas. Culture of purulent discharge yielded the growth of anaerobic organisms. Surgical drainage was performed immediately and debridement of necrotic tissue in the involved areas was often repeated. At the same time, the patient received antibiotic therapy that included agents effective against anaerobic bacteria. However, the scrotal skin developed gangrene and the right testis hung suspended with cord exposed. This testis was intact. The scrotal skin defect was cured using a skin graft, after the infection had been brought under control.

Adult↗

Neurogenic vasodilation and release of calcitonin gene-related peptide (CGRP) from perivascular nerves in the rat mesenteric artery.

The effect of perivascular nerve stimulation (PNS) on the release of calcitonin gene-related peptide (CGRP) was examined by radioimmunoassay (RIA) in isolated, perfused rat mesenteric arteries. The released CGRP-like immunoreactivity (CGRP-LI) was identified to be CGRP itself and its oxidized form by combined analysis with RIA and high performance liquid chromatography. CGRP-LI was localized in the perivascular nerves of the large mesenteric artery and its branches. In the preparation precontracted by methoxamine, and perfused with a solution containing guanethidine, an adrenergic neuron blocker, PNS induced vasodilator responses and an increase of CGRP-LI in the perfusate in a frequency-dependent manner. Both the responses were attenuated by tetrodotoxin (10(-6) M), suggesting that they were neurogenic in origin. Removal of Ca2+ from the perfusing solution also abolished the PNS-induced release of CGRP-LI. These findings suggest that CGRP plays a transmitter role in the neurogenic vasodilation in the rat mesenteric vascular bed.

Animals↗

Endothelin-3 is a novel neuropeptide: isolation and sequence determination of endothelin-1 and endothelin-3 in porcine brain.

The molecular forms of endothelin (ET) related peptides were investigated in porcine brain by using high performance liquid chromatography coupled with three specific radioimmunoassays. ET-1 and its oxidized form were isolated and sequenced as in the case of porcine spinal cord. A very small amount of big ET-1 (1-39) and its C-terminal fragment (big ET-1 (22-39] were also detected. Furthermore, immunoreactive (ir)-ET-3 was isolated and sequenced; its partial primary structure was identical to that of human (rat) ET-3. The concentrations of ir-ET-1 and ir-ET-3 in porcine brain were 140 fmol/g tissue and 5 fmol/g tissue, respectively. These results indicate that besides ET-1, ET-3 is a novel neuropeptide in the central nervous system.

Amino Acid Sequence↗

Isolation and characterization of the rat catalase-encoding gene.

Using cDNA clones coding for rat liver catalase (hydrogen peroxide:hydrogen peroxide oxidoreductase, EC 1.11.1.6), overlapping genomic clones were isolated. By Southern blotting analysis and nucleotide sequencing, the gene was characterized to be about 33 kb in length and to have 13 exons and twelve introns. S1 mapping and primer extension analyses showed the presence of multiple transcription start points (tsp) located between 66 bp and 105 bp upstream from the translational start codon. Nucleotide sequence immediately upstream from the tsp lacks the TATA box but contains multiple CCAAT boxes and GC-like boxes.

Amino Acid Sequence↗

Presence of endothelin-1 in porcine spinal cord: isolation and sequence determination.

We investigated the molecular forms of endothelin (ET) related peptides in porcine spinal cord by high performance liquid chromatography coupled with radioimmunoassays using three antisera raised against ET-1 and C-terminal fragments of ET-1 and big ET-1. ET-1 and its oxidized form were isolated as major immunoreactive peptides and sequenced. Furthermore, immunoreactivities like ET-3 and big ET-1(22-39) (contents: less than 8% and less than 1% of ET-1, respectively) were detected based on their chromatographic retention times and characteristics of immunoreactivity to the antisera. Big ET-1 was only scarcely detected. Immunohistochemical study showed the presence of ET-1-like immunoreactivity in motoneurons, dorsal horn neurons and dot- and fiber-like structures in the dorsal horn of lumbar spinal cord. These results indicate that ET-1 is present not only in endothelial cells but also in spinal cord, and that big ET-1 is converted into ET-1 in spinal cord by specific processing between Trp21-Val22. The data also indicate that ET-1 may act as a neuropeptide in the central nervous system.

Amino Acid Sequence↗

Endothelin-1 induces vasoconstriction through two functionally distinct pathways in porcine coronary artery: contribution of phosphoinositide turnover.

Endothelin-1 (ET1)-induced contraction of isolated porcine coronary artery strips was previously reported to be mainly dependent on extracellular Ca2+. However, even in a Ca2+-free, EGTA-containing solution relatively high concentrations of ET1 induced a weak vasoconstriction, which was markedly but not completely inhibited by pretreatment with caffeine. Over similar dose ranges, ET1 stimulated the production of inositol phosphates in a dose-dependent manner in intact arterial tissues, which was independent of extracellular Ca2+ and was not affected by receptor blockers such as atropine, methysergide and diphenhydramine. Moreover, ET1 was shown to induce an increase in 1,2-diacylglycerol. These results indicate that the activation of ET1 receptors on porcine coronary artery smooth muscle causes phosphoinositide breakdown, leading to intracellular Ca2+ mobilization and protein kinase C activation. It is suggested that phospholipase C-mediated phosphoinositide breakdown as well as previously reported activation of voltage-dependent Ca2+ channels are involved in the mechanism of ET1-induced vasoconstriction.

Animals↗

Vasoconstrictor response of large cerebral arteries of cats to endothelin, an endothelium-derived vasoactive peptide.

Endothelin, a 21-amino acid peptide produced by vascular endothelial cells, caused a sustained constriction of isolated large cerebral arteries of cats in a dose-dependent manner. The increased tone of the tissue did not return to the resting level after repeated washings. No vasodilator response was evoked by endothelin in the presence of an active tone. The contractile response of cerebral arteries was not inhibited by rubbing of the endothelium, cold storage denervation or indomethacin. In contrast, nicardipine or diltiazem antagonized the endothelin-induced contraction non-competitively. No contraction was evoked by endothelin in a Ca2+-free solution while the addition of Ca2+ ions in the presence of endothelin in a Ca2+-free solution caused a sustained contraction. Ca2+-induced contraction in the Ca2+-free solution containing endothelin was also inhibited by nicardipine. Therefore, endothelin causes a direct contraction of the smooth muscles of cat cerebral arteries, probably by activating the influx of Ca2+ ions through L-type Ca2+ channels of smooth muscles.

Animals↗

Activated partial thromboplastin time-protamine dose relation in the presence and absence of heparin.

A protamine titration is one of the methods to determine the protamine dose necessary to neutralize heparin. The protamine dose response was studied with the activated partial thromboplastin time (APTT) in the presence of a known amount of heparin and in the absence of heparin, using freshly prepared human plasma. When heparin was present in the plasma, APTT values plateaued between a minimal neutralizing dose of protamine and a protamine dose five times greater. At doses above the APTT plateau, protamine exerted its own anticoagulant action as evidenced by an increase in APTT values. In the absence of heparin, APTT did not change until the protamine concentration reached 50 micrograms/mL. Then the APTT began to increase above this critical concentration. The increases in APTT values caused by an increase of 50 micrograms/mL of protamine were significantly greater without heparin than they were in the presence of heparin. These results suggest that protamine has a wide safety range when neutralizing heparin without exerting its own anticoagulant action. Although the mechanisms are under speculation, the heparin-protamine complex may inhibit the anticoagulant action of protamine in vitro.

Blood Coagulation↗

Membrane filters for the concentration of trace elements in water: distribution of ion pairs between membrane filter and aqueous phases.

The sorption of ion pairs on membrane filters (MFs) has been studied by taking the membrane filter as one of the homogeneous phases. The sorbability of some ionic species and the sorption abilities of different types of MF were evaluated in terms of the sorption constant defined by Ksor,CA = [(C+,A-)f]/[C+][A-], where C+, A- and (C+,A-) refer to the cation, anion and the ion pair, respectively, and f refers to the filter phase. The values of Ksor,CA were determined for many combinations of ionic complexes of cobalt(III) with pyridylazophenols, either as cations or anions, and oppositely charged organic ions having different alkyl chain lengths, with MFs made of different materials: nitrocellulose (NC; Toyo Advantec), acetylcellulose (AC; Fuji Film), regenerated cellulose (RC; Toyo Advantec) and polyethersulphone (PS; Toyo Advantec). For a given cobalt complex ion, the value of log Ksor,CA increased linearly with the increasing number of carbons in the counter ion. Membrane filters made of different materials showed different sorption abilities, the order being NC greater than PS greater than RC greater than AC. It was shown that the surface area of the MF is of greater significance than the volume of the matrix of the MF in determining the sorption constant.

Elements↗

Endothelin activates the dihydropyridine-sensitive, voltage-dependent Ca2+ channel in vascular smooth muscle.

Endothelin is a potent endothelium-derived vasoconstrictor peptide recently characterized from porcine and human vascular endothelial cells. Here we provide evidence that endothelin activates the dihydropyridine-sensitive, voltage-dependent Ca2+ channel in porcine coronary artery smooth muscle. The vasoconstrictor action of endothelin is efficiently antagonized by low doses of the dihydropyridine Ca2+-channel blocker nicardipine. Endothelin augments the Ca2+-induced contraction in a high-K+ depolarizing solution, markedly enhances high-threshold Ca2+-channel current on the whole-cell patch clamp recording, and causes a sustained increase in the intracellular Ca2+ that is largely dependent on extracellular Ca2+. These findings suggest that endothelin exerts its vasoconstrictor effect by either directly or indirectly activating the voltage-dependent Ca2+ channel.

Animals↗