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Biomedical subjects

S Suga

Publications and source records attributed to S Suga.

At least 253 records · Page 14Linked to original sources
PubMed1991

Molecular cloning of a non-isopeptide-selective human endothelin receptor.

We isolated several complementary DNA (cDNA) clones encoding a non-isopeptide-selective human endothelin receptor (ETBR) from a human placenta cDNA library. The clones, different in the length of their 3'-untranslated regions, encoded the same 442-amino acid protein with a transmembrane topology similar to that of other G protein-coupled receptors. The rank order of the binding of ET isopeptides (ET-1, ET-2 and ET-3) to the receptor expressed in COS-7 cells was ET-1 = ET-2 = ET-3. Northern blot analysis identified three mRNA species, 4.3 kb, 2.7 kb and 1.7 kb in size, probably generated by their use of alternative polyadenylation sites. These mRNAs were expressed in a wide variety of human tissues, at the highest level in the brain and at a significant level in cultured endothelial cells.

Amino Acid Sequence↗
PubMed1991

Acute pulmonary alveolar hypoxia increases lung and plasma endothelin-1 levels in conscious rats.

To investigate the effect of pulmonary alveolar hypoxia on the synthesis and release of endothelin (ET)-1, ET-1-like immunoreactivity (-LI) levels of the lung and plasma were measured in conscious unrestrained rats under hypoxic conditions. Sixty-min exposure to alveolar hypoxia (10% O2 or 5% O2) increased the ET-1-LI level in the lung. The plasma ET-1-LI level in hypoxic rats also increased significantly. The increase of plasma and lung ET-1-LI levels were parallel to the severity of hypoxia. These results demonstrates that acute pulmonary alveolar hypoxia increases lung and plasma ET-1-LI levels in conscious unrestrained rats, suggesting a possible physiological or pathophysiological significance of ET in alveolar hypoxia.

Animals↗
PubMed1991

Severity of human herpesvirus-6 viremia and clinical findings in infants with exanthem subitum.

The degree of viremia with human herpesvirus-6 was evaluated in 176 blood samples from 89 infants with exanthem subitum and viremia, and compared with the severity of clinical features and complications of the disease. Fever persisted for 3 to 4 days in 73% of infants and for more than 5 days in 22%, followed by a rubella- or measles-like rash. The viremia was observed between the first day of fever (day 0) and day 4 of the disease. The number of infected cells per 10 million mononuclear cells was 3.45 +/- 1.00 (log10, mean +/- SD) on days 0 to 2, 3.30 +/- 1.14 on day 3, and 3.09 +/- 2.05 on day 4 of the disease. The number of infected cells on days 3 to 4 in infants with a febrile period longer than 4 days and free virus in plasma was significantly greater than that in infants with a febrile period of less than 3 days and without free virus in plasma. The amount of virus in blood on days 0 to 2 did not relate to the duration of fever, and that on days 0 to 4 did not relate to the presence or absence of diarrhea, bulging fontanelle, or bronchopneumonia. These findings suggest that the magnitude of the virus replication in infants with exanthem subitum is reflected in the severity of the disease.

Exanthema Subitum↗
PubMed1991

Pathophysiological role of augmented atrial natriuretic polypeptide gene expression in DOCA-salt hypertension. Effects of atrial natriuretic polypeptide monoclonal antibody.

To elucidate the pathophysiological significance of endogenous atrial natriuretic polypeptide (ANP) in hypertension, we investigated the biosynthesis and secretion of ANP in deoxycorticosterone acetate (DOCA)-salt hypertensive rats and also examined the effect of passive immunization with monoclonal antibody raised against alpha-rat ANP on the development of hypertension in DOCA-salt rats. The plasma ANP level in DOCA-salt rats was significantly elevated in comparison to control rats. While the atrial ANP concentration in DOCA-salt rats was not significantly altered, the atrial level of ANPmRNA in DOCA-salt rats was two-fold higher than that in control rats. These results suggest the augmented biosynthesis of ANP in the atrium and the oversecretion of ANP from the heart in DOCA-salt rats. The levels of ANP and ANPmRNA in the ventricle of DOCA-salt rats exhibited significant increases, compared with those in control rats, suggesting the induction of ANP gene expression in the ventricle of DOCA-salt hypertensive rats under pre/after overload. Weekly intravenous administrations of monoclonal antibody with high affinity for alpha-rat ANP significantly augmented the rise in blood pressure of DOCA-salt rats. These results support the hypothesis that the augmented secretion of ANP is one of the defensive mechanisms to counteract high arterial pressure in this model of hypertension.

Animals↗
PubMed1991

Isolation and characterization of porcine endothelin-like peptide.

Two endogenous molecules possessing an endothelin-like sequence with an apparent molecular weight of 7 kDa were isolated from serum-free culture medium of porcine aortic endothelial cells, using a specific radioimmunoassay. N-terminal sequences of two molecules were identical to each other and were Ser-Leu-Lys-Asp-Leu-Phe-Pro-Ala-Lys-Ala-Ala-Asp-Arg-Arg-Asp-Arg-X-Gln-X- Ala-X- Gln-Lys-Asp, which corresponds to the sequence [94-117] of preproendothelin-1. This finding indicates that these two molecules may be closely related peptides such as the oxidized form or disulfide analogues and also suggests that the endogenous peptide possessing an endothelin-like sequence is generated by proteolytic cleavage at paired basic amino acids Arg92-Arg93. Further studies on the structure and function of new endogenous peptides possessing an endothelin-like sequence are ongoing in our laboratory.

Amino Acid Sequence↗
PubMed1991

Endothelin in patients with chronic renal failure.

To investigate the pathophysiological significance of endothelin-1 (ET-1) in renal failure, we measured plasma and urine concentrations of ET-1-like immunoreactivity (LI) by radioimmunoassay (RIA). The plasma ET-1-LI level was significantly increased in hemodialyzed and nonhemodialyzed patients with chronic renal failure (CRF). The increase in the plasma ET-1-LI level in CRF was much larger than that in other diseases in which the plasma ET-1-LI level was reported to be increased. The urine ET-1-LI level was lower, and daily excreted amounts of ET-1-LI were smaller in CRF patients than in normal subjects. These findings indicate that the increased plasma level of ET-1-LI in CRF results from the decreased clearance rate of ET-1-LI in the kidney. Gel permeation chromatographic analysis revealed that ET-1-LI in plasma from CRF consisted of small and large molecular forms of ET-1-LI. The small molecular form is presumably ET-1, and large molecular forms are big ET-1 and another component with the molecular weight of 6,000 as is the case of that in normal plasma (1). However, the ratio of the smaller to large molecular forms of ET-1-LI in CRF was 1:13 and was quite different from that in normal plasma (1:4). These observations clearly indicate that the elevation of plasma ET-1-LI level in CRF was mainly due to the increase in the large molecular form of ET-1-LI.

Chromatography, Gel↗
PubMed1991

A cooperative randomized study on tegafur plus mitomycin C versus combined tegafur and uracil plus mitomycin C in the treatment of advanced gastric cancer.

A randomized controlled trial involving 13 institutions in Japan was conducted in order to compare the efficacy of tegafur plus mitomycin C (MMC) (Regimen A) and UFT (a combination of uracil and tegafur at a molar ratio of 4 to 1) plus MMC (Regimen B) for patients with advanced gastric cancer, who had not received any prior cancer chemotherapy. Regimen A (tegafur + MMC) consisted of 5 mg of MMC/m2/week given intravenously, and 500 mg of tegafur/m2/day given orally. Regimen B consisted of the same schedule of MMC and 375 mg of UFT/m2/day given orally. One hundred and eighty-six patients with primary gastric cancer were entered; 183 were eligible and 3 were ineligible for the study. A total of 169 were evaluable for efficacy of the treatment, including 90 patients with Regimen A and 79 with Regimen B. A response rate of 7.8% (7/90 cases) for Regimen A and one of 25.3% (20/79 cases) for Regimen B were obtained, indicating a significantly higher response rate for Regimen B according to the Criteria for Evaluating Efficacy of Chemotherapy/Radiation Therapy in the Treatment of Gastric Cancer (P = 0.004). Regarding side effects, no marked differences in either severity or incidence were observed between the two groups. The group assigned to Regimen B showed a significant survival advantage after adjustment for major prognostic factors using a proportional hazards model (P = 0.0398). Moreover, a close correlation of antitumor effect and survival duration was found when the above criteria were used.

Administration, Oral↗
PubMed1991

Biosynthesis, secretion, and receptor selectivity of human brain natriuretic peptide.

Biosynthesis, secretion and receptor selectivity of human brain natriuretic peptide (hBNP) were studied. The BNP mRNA level in the ventricle was approximately 40% of that in the atrium and, taking tissue weight into account, the total amount of BNP mRNA in the ventricle was about twofold greater than the total amount in the atrium. The plasma BNP-like immuno-reactivity (-LI) level in normal subjects was 0.90 +/- 0.07 fmol/mL, which was 16% of the ANP-LI level. In contrast, the plasma BNP-LI level markedly increased in patients with congestive heart failure, with a progressive rise in proportion to its severity. There was a significant step-up of the plasma BNP-LI level in the coronary sinus (CS) compared with that in the aortic root, and the difference in the plasma BNP-LI level between the CS and the aorta (Ao), delta (CS-Ao)BNP, increased with the severity of congestive heart failure. In addition, the difference in the BNP-LI level between the anterior inverventricular vein (AIV) draining the ventricle and the aorta (delta (AIV-Ao)BNP) was comparable to delta (CS-Ao) BNP, indicating that BNP is secreted predominantly from the ventricle. Binding ability to human clearance receptors (C receptors) and cyclic GMP (cGMP) production of hBNP were investigated and compared with those of ANP. hBNP bound to human C receptors very weakly (about 7%), but exerted cGMP production similar to ANP in cultured human mesangial cells and bovine endothelial cells. In conclusion, hBNP is a novel cardiac hormone mainly synthesized in and secreted from the ventricle and plays physiological and pathophysiological roles in the dual cardiac natriuretic peptide system.

Adolescent↗
PubMed1991

Expression of brain natriuretic peptide gene in human heart. Production in the ventricle.

To elucidate the expression of the brain natriuretic peptide gene in the human heart, we have measured brain natriuretic peptide mRNA levels in hearts using the Northern blot hybridization method. Brain natriuretic peptide mRNA was present with a size of approximately 0.9 kb in the ventricle as well as in the atrium. The brain natriuretic peptide mRNA level in the ventricle was 52% of that in the atrium, whereas the atrial natriuretic peptide mRNA level in the ventricle was approximately two orders of magnitude lower than that in the atrium. Taking atrial and ventricular weights into account, the total amount of brain natriuretic peptide mRNA in the ventricle represented 77% of that in the whole heart. These results demonstrate that most of brain natriuretic peptide mRNA occurs in the ventricle, in contrast with atrial natriuretic peptide mRNA, which is present mainly in the atrium, indicating that the ventricle is a major production site of brain natriuretic peptide.

Aged↗
PubMed1991

Natriuretic peptides as cardiac hormones in normotensive and spontaneously hypertensive rats. The ventricle is a major site of synthesis and secretion of brain natriuretic peptide.

To study synthesis, storage, and secretion of brain natriuretic peptide (BNP) in the heart, we have measured BNP mRNA and BNP concentrations in the hearts of Wistar-Kyoto rats and also have investigated its secretion from the isolated perfused heart. The atrium expressed the BNP gene at a high level, and a considerable amount of BNP mRNA also was present in the ventricle, which corresponded to approximately 40% of the atrial BNP mRNA concentration. When tissue weight was taken into account, the total content of BNP mRNA in the ventricle was approximately threefold larger than that in the atrium, although the atrial natriuretic peptide (ANP) mRNA content in the ventricle was only 7% of that in the atrium. By contrast, the BNP concentration in the ventricle was 4.07 +/- 0.97 pmol/g, which was less than 1% of that in the atrium (451 +/- 86 pmol/g). The basal secretory rate of BNP from the isolated perfused whole heart was 49.3 +/- 6.1 fmol/min, approximately 60% of which was maintained even after atrial removal, whereas the secretory rate of ANP was reduced to less than 5%. We also studied age-matched spontaneously hypertensive rats-stroke prone. The rank order of the BNP mRNA concentration in the hearts of these rats was left ventricle greater than right ventricle greater than right atrium = left atrium, and the total BNP mRNA content and BNP secretory rate in the ventricle were twice as large as in Wistar-Kyoto rats. These results demonstrate that BNP is a novel cardiac hormone in rats and is predominantly synthesized in and secreted from the ventricle. This is in striking contrast to ANP, which occurs mainly in the atrium. The results also suggest possible pathophysiological roles of BNP in certain cardiovascular disorders.

Animals↗
PubMed1991

Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide.

Using a specific radioimmunoassay for human brain natriuretic peptide (hBNP) with a monoclonal antibody, we have investigated its synthesis, secretion, and clearance in comparison with those of atrial natriuretic peptide (ANP) in normal subjects and patients with congestive heart failure (CHF). Mean BNP-like immunoreactivity (-LI) levels in normal atrium and ventricle were 250 and 18 pmol/g, respectively. The plasma BNP-LI level in normal subjects was 0.90 +/- 0.07 fmol/ml, which was 16% of the ANP-LI level. In contrast, the plasma BNP-LI level markedly increased in patients with CHF in proportion to its severity, and surpassed the ANP-LI level in severe cases. There was a significant step-up of the plasma BNP-LI level in the coronary sinus (CS) compared with that in the aortic root (Ao) and the difference between these BNP-LI levels, delta(CS-Ao)BNP, also increased with the severity of CHF. In addition, the step-up of the BNP-LI level in the anterior interventricular vein [delta(AIV-Ao)BNP] was comparable to delta(CS-Ao)BNP, indicating that BNP is secreted mainly from the ventricle. Predominant BNP synthesis in the ventricle was also confirmed by Northern blot analysis. Catheterization and pharmacokinetic studies revealed that hBNP is cleared from the circulation more slowly than alpha-hANP; this was in part attributed to lower (about 7%) binding affinity of hBNP to clearance receptors than that of alpha-hANP. A predominant molecular form of BNP-LI in the heart and plasma was a 3-kD form corresponding to hBNP. These results indicate that BNP is a novel cardiac hormone secreted predominantly from the ventricle, and that the synthesis, secretion and clearance of BNP differ from those of ANP, suggesting discrete physiological and pathophysiological roles of BNP in a dual natriuretic peptide system.

Antibodies, Monoclonal↗
PubMed1991

C-type natriuretic peptide (CNP) in rats and humans.

We have established a specific radioimmunoassay (RIA) for C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, and have elucidated its tissue distribution and molecular form. In rats, high concentrations of CNP-like immunoreactivity (-LI) were detected in the anterior lobe (19.8 +/- 8.6 pmol/g) and neurointermediate lobe (4.64 +/- 0.74 pmol/g) of the pituitary gland. CNP-LI was present throughout the brain with its high concentrations in the hypothalamus and cerebellum. Small amounts of CNP-LI were also detected in the lower part of gastrointestinal tract and the kidney. However, no significant amount of CNP-LI was present in other organs including the heart. Considerable amounts of CNP-LI were detected throughout the human brain. High performance-gel permeation chromatography coupled with the RIA detected two peaks of CNP-LI in the rat brain; CNP and presumably its N-terminally elongated form with 53 amino-acid residues, CNP-53. These findings indicate that the tissue distribution and processing pattern of CNP are clearly different from those of atrial natriuretic peptide and brain natriuretic peptide and suggest possible roles of CNP as a neurotransmitter or neuromodulator rather than as a cardiac hormone.

Animals↗