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T Masaki

Publications and source records attributed to T Masaki.

At least 325 records · Page 18Linked to original sources

Molecular characterization of endothelin receptors.

Following the first report on the identification of endothelin (ET), an increasing body of work has accumulated on this endothelium-derived 21-amino acid vasoconstrictor peptide. Subsequently, the existence of three distinct isoforms of ET, designated ET-1, ET-2 and ET-3, was predicted from the finding of three separate genes. The differential potencies of the three isoforms of the ET family have opened up the possibility of the existence of multiple ET receptor subtypes. Recently, molecular biological techniques provided direct evidence of at least two distinct subtypes of ET receptor. This article discusses the functions of the ETs, focusing especially on the molecular characteristics of their receptors.

Amino Acid Sequence↗

Factor I-dependent inactivation of human complement C4b of the classical pathway by C3b/C4b receptor (CR1, CD35) and membrane cofactor protein (MCP, CD46).

Proteolytic inactivation of C4b is a crucial step for regulation of the classical complement pathway. A plasma protease factor I and membrane cofactors, C3b/C4b receptor (CR1) and membrane cofactor protein (MCP), participate in the regulation of cell-bound C4b although the physiological potency of these cofactors remains unknown. We have examined the optimal conditions of the factor I-mediated C4b regulatory system using purified cofactors. CR1 being a cofactor at a cofactor/C4b ratio less than 0.1 (w/w), fluid phase C4b, and methylamine-treated C4 (C4ma) were degraded by factor I into C4bi: minimal Cd4 was generated in the fluid phase. Liposome-bound C4b (LAC4b), on the other hand, was degraded into C4c and C4d. CR1 showed two optimal pHs (6.0 and 7.5) for fluid phase C4b, but one (6.0) for LAC4b, and in both cases low conductivity conditions enhanced the C4bi generation. CR1 cofactor activity was barely influenced by the NP-40 concentration. On the other hand, MCP degraded C4b and C4ma, as a factor I-cofactor, more efficiently into C4c and C4d. Though MCP cofactor activity, like that of CR1, was enhanced under low conductivity conditions, it has only one optimal pH, 6.0, in both fluid and solid phases. Furthermore, as in the case of C3b cleavage, a sufficient NP-40 concentration to solubilize membrane was needed for MCP to express full cofactor activity for C4b, in contrast to CR1. MCP was less potent for C4b inactivation than for C3b inactivation, while CR1 acted as a slightly more effective cofactor for C4b cleavage than for C3b cleavage.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗

Isolation of cDNA for bovine stomach 155 kDa protein exhibiting myosin light chain kinase activity.

Two proteins with myosin light chain kinase activity and electrophoretic molecular weights of 155,000 and 130,000 were each isolated from bovine stomach smooth muscle [Kuwayama, H., Suzuki, M., Koga, R., & Ebashi, S. (1988) J. Biochem. 104, 862-866]. The 155 kDa component showed a much higher superprecipitation-inducing activity than the 130 kDa component, when compared on the basis of equivalent myosin light chain kinase activity. In this study, we isolated a cDNA for the entire coding region of the 155 kDa protein. The deduced amino acid sequence revealed a high degree of similarity to those of chicken and rabbit smooth muscle myosin light chain kinases. Multiple motifs, such as three repeats of an immunoglobulin C2-like domain, a fibronectin type III domain, and unusual 20 repeats of 12 amino acids were detected in the sequence. Part of the amino-terminal sequence was similar to that of the actin- and calmodulin-binding domain of smooth muscle caldesmon. These observations suggest that the 155 kDa protein has additional functions other than its enzymatic activity. Two mRNAs of 6.0 and 2.6 kb in length in the bovine stomach smooth muscle RNAs were hybridized with cDNA probes. The 2.6-kb RNA probably encodes telokin, which is the carboxyl terminus of smooth muscle myosin light chain kinase. mRNAs with identical lengths were also detected in bovine aorta.

Amino Acid Sequence↗

A pertussis toxin-sensitive mechanism of endothelin action in porcine coronary artery smooth muscle.

1. Endothelin-1 (ET-1)-induced contraction of porcine coronary artery strips may be mediated via at least two intracellular signalling mechanisms, the activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels and the stimulation of phosphoinositide breakdown. Here we have investigated the possible involvement of pertussis toxin (PT)-sensitive guanosine-5'-triphosphate (GTP)-binding proteins (G-proteins) in ET-1-induced activation of these two signalling pathways in porcine coronary artery smooth muscle. 2. Increase in extracellular K+ concentration (10, 15 mM) shifted the dose-response relationship for the ET-1-induced contraction to the left. 3. The dihydropyridine Ca2+ channel blocker, nifedipine (10(-8) M), induced a rightward shift in the dose-response curve for ET-1. Pretreatment of the arterial strips with PT (0.1 microgram ml-1) induced a similar rightward shift of the ET-1 dose-response curve but not of the KCl response. Nifedipine (10(-8) M) did not further attenuate the ET-1-induced contraction in the PT-pretreated strips. 4. The pretreatment with PT significantly reduced 45Ca2+ uptake of the arterial strips stimulated by ET-1, but had no effect on ET-1-induced production of inositol phosphates. 5. The contractile response of the arterial strips to phorbol dibutyrate, an active phorbol ester, was not significantly affected by 10(-8) M nifedipine. 6. We confirmed that the pretreatment of the tissue with PT induced ADP-ribosylation of a 41 kDa membrane protein. 7. These findings indicate that activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels by ET-1 in this tissue is mediated via a PT-sensitive G-protein in a manner apparently independent of the ET-1-induced activation of protein kinase C. It is concluded that the action of ET-1 in porcine coronary artery is mediated via two distinct signal transduction pathways, which are coupled to PT-sensitive and PT-insensitive GTP-binding proteins, respectively.

Adenosine Diphosphate Ribose↗

[Studies on Clostridium absonum isolates from clinical specimens].

Two strains of Clostridium absonum isolated from clinical specimens and a type strain were tested for heat resistance of spores, biochemical properties and neutralization of their lecithinase by anti-C. perfringens alpha toxin antiserum. In addition, the usefulness of RapID ANA (AMUCO) and ANIDENT (API) kits for the identification of C. absonum was examined. The results were summarized as follows: 1. C. absonum isolates from clinical specimens were resistant against heating at 70 degrees C for 10 min and a type strain against heating at 85 degrees C for 10 min, less resistant than those of C. perfringens BP6K. 2. C. absonum differentiated from C. perfringens in fermentation of trehalose, melibiose and raffinose, and hydrosis of esculin and starch. 3. Lecithinase of C. absonum was not completely neutralized by anti-C. perfringens alpha toxin antiserum. 4. Both RapID ANA and ANIDENT kits were useful for differentiation of C. absonum from C. perfringens but not for the identification of C. absonum.

Adolescent↗

Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells.

To elucidate the cellular mechanism of endothelin-1 biosynthesis induced by angiotensin and vasopressin, we first cloned and sequenced full-length bovine preproendothelin-1 complementary DNA (cDNA) from a cultured bovine carotid artery endothelial cell cDNA library. The predicted bovine preproendothelin-1 consists of 202 amino acid residues and has a high percentage of homology to human, porcine, and rat preproendothelin-1 (70%, 81%, and 77%, respectively). Big endothelin-1, an intermediate form, consists of 39 residues differing only at position Val28 from porcine (Ile28) and His27 from rat (Arg27). The predicted 21-residue mature endothelin-1 is identical to human, porcine, rat, canine, and mouse endothelin-1. Northern blot analysis with the cloned cDNA as a probe demonstrated that a single 2.3-kb preproendothelin-1 messenger RNA (mRNA) is expressed not only in endothelial cells, but also in various bovine tissues, including lung, brain, heart, intestine, kidney, ovary, and urinary bladder. Angiotensin II and arginine vasopressin immediately and dose-dependently induced expression of preproendothelin-1 mRNA, whose effects were abolished by specific receptor antagonists. These findings suggest that stimulation of endothelin-1 secretion from endothelial cells by both agonists may be principally due to induction of preproendothelin-1 mRNA.

Amino Acid Sequence↗

[A novel function of tetrahydrobiopterin].

6R-L-erythro-5, 6, 7, 8-Tetrahydrobiopterin (6R-BH4) is known as a cofactor for the hydroxylases of phenylalanine, tyrosine and tryptophan and also as a cofactor for nitric oxide synthase. Recently, a novel function of 6R-BH4 has been found: that is, 6R-BH4 acts on specific membrane receptors to directly stimulate the release of monamine neurotransmitters such as dopamine and serotonin, independently of its cofactor activity. In addition, it indirectly stimulates the release of non-monoamine neurotransmitters such as acetylcholine and glutamate, through activation of monoaminergic systems. In this paper, we briefly review recent experimental data, which provide new insights into the role of 6R-BH4 as a regulator of neuronal function. We also discuss the possibility of treatment by 6R-BH4 of neuropsychiatric diseases such as Parkinson's disease, Alzheimer's disease, depression and infantile autism.

Alzheimer Disease↗

Inhibition of Achromobacter protease I by lysinal derivatives.

Z-Val-, Z-Pro-, Z-Leu-Leu-, and Z-Leu-Pro-lysinals and BZ-DL-lysinal were chemically synthesized and tested as novel inhibitors for Achromobacter protease I (API), a lysine-specific serine protease. Among the lysinal derivatives tested, Z-Val-lysinal was the most potent competitive inhibitor, its Ki being estimated as 6.5 nM in an esterolytic assay with Tos-Lys-OMe. In an amidolytic assay, Z-Leu-Leu-lysinal was the most potent inhibitor and the apparent mode of inhibition was non-competitive. The Kis of the other lysinal derivatives in both esterolytic and amidolytic assays were more than 10(3) times lower than that of leupeptin. Z-Val-lysinol, lacking the aldehyde group, was a poor competitive inhibitor. These results suggest that acyl-, acylaminoacyl-, and acylpeptidyllysinals function as a transition-state inhibitor for Achromobacter protease I.

Alcaligenes↗

Biochemical analysis of the bone of SHC rats with spontaneous hypercholesterolemia and renal dysfunction.

Spontaneously hypercholesterolemic (SHC) rats exhibit severe abnormalities in renal function and bone metabolism at old ages, in addition to hypercholesterolemia. SHC rats were also found to show endocrine abnormalities such as hyperthyroidism from young ages. In this study, biochemical and microdensitometric analyses were carried out using femurs to characterize further the abnormality in bone metabolism: whether biochemical markers of the bone may be affected by these abnormalities. At 6 weeks of age, the ashed weight and calcium content of the dried femurs were slightly lower in SHC rats than in age-matched Sprague-Dawley (SD) rats. None of the markers of microdensitometric analysis was changed. At 24 weeks of age, the ashed weight of dried femurs and the density of the marrow region of femurs were lower in the SHC rats. The results indicate that SHC rats exhibit severe abnormality in bone metabolism leading to biochemical changes in the bone at old ages whereas changes in bone markers were minimal at young ages before the onset of severe renal dysfunction.

Animals↗

Endothelins.

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Amino Acid Sequence↗

Endothelin-1 mediates regional blood flow during and after pulmonary operations.

To investigate the role of endothelin-1, a potent vasoconstrictor peptide produced by vascular endothelial cells, in the physiologic response to surgical stress, we measured plasma endothelin-1 concentrations by a sandwich-enzyme immunoassay in patients with lung cancer undergoing pulmonary operations (n = 12). In the first group (n = 6), we measured plasma endothelin-1 concentrations at multiple sampling sites (median cubital vein, pulmonary artery, and left atrium). Plasma endothelin-1 levels were significantly increased at all sampling sites at the end of the operation. Although there was no difference between the increased plasma levels of endothelin-1 in the pulmonary artery and in the left atrium, the increased level in the median cubital vein (peripheral venous blood) was significantly higher than that in the pulmonary artery (mixed venous blood). This result suggests that the production of endothelin-1 might differ between various organs under surgical stress. In the second group (n = 6), we measured plasma endothelin-1 concentrations both in the median cubital vein and in the ipsilateral radial artery, and also measured cardiac output and forearm blood flow. The increase in endothelin-1 levels in the median cubital vein was significantly higher than that in the radial artery after the operation. The endothelin-1 output from the forearm, calculated by the forearm blood flow and the arteriovenous difference of endothelin-1 concentrations, significantly increased after the operation. Although the cardiac output significantly increased after the operation, the forearm blood flow significantly decreased. The present findings provide a novel hypothesis that the preferential release of endothelin-1 from the peripheral vasculature of the forearm may partly contribute to a compensatory response to surgical stress, for example, the reduction of local blood flow in nonvital organs so as to increase the blood flow in vital organs.

Adult↗

[Continuous intra-arterial infusion chemotherapy in colorectal cancer patients with nonresectable metastatic liver cancer].

Five colorectal cancer patients with nonresectable metastatic liver cancer underwent continuous intraarterial chemotherapy in our institute from January to December 1991. Patients included four rectal cancers and one colonic cancer. 5-fluorouracil (5-FU) was infused continuously through an Infuse-A-Port; 360 mg/m2/day for one week after operation, and 180 mg/m2/day for the following three weeks. Since the fifth week after operation, two weeks without infusion and two weeks of infusion (180 mg/m2/day) were alternated as long as possible. Total periods of 5-FU infusion therapy were from one to 11 months and total doses of 5-FU ranged from 8,750 mg to 25,650 mg. Three patients showed partial response (PR) and two patients progressive disease (PD) (response rate; 60%). In three cases of PR, lengths of infusion therapy and total doses of 5-FU before PR was first observed was 8 weeks, 10,750 mg, 6 weeks, 9,250 mg, and 4 weeks, 8,750 mg, respectively. Four patients presented nausea, appetite loss or abdominal pain, which were considered to be side effects of 5-FU. In one of these four patients, infusion could not be continued because symptoms were so severe. However, catheter troubles were not noticed among all cases.

Colonic Neoplasms↗

[Relationship between arterial blood gas tensions and a clinical scoring system in asthmatic patients].

We evaluated the relationship between blood gas tensions and a clinical scoring system in pediatric asthma patients, who were divided into two groups according to their ages (under 5 years and over 6 years). The clinical score was derived from Mitsui, which was constructed using reference only to clinical symptoms and signs. The clinical scores had a statistically significant correlation with PaO2, PaCO2, SaO2 and pH in both groups. However there were fluctuations between clinical score and blood gas tensions. A low clinical score did not exclude hypoxemia. There were no statistical differences between the two groups, but subjects under 5 years old showed better correlation. This scoring system is useful to evaluate the degree of asthma attack, especially severe attack, both in younger (under 5 years) and older (over 6 years) asthmatic patients.

Adolescent↗