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H Matsuo

Publications and source records attributed to H Matsuo.

At least 361 records · Page 20Linked to original sources

[Effect of histamine H2-receptor antagonists on the phosphorus-binding ability of phosphate binders in hemodialysis patients].

We examined the effects of histamine H2-receptor antagonists on the phosphorus binding ability of phosphate binders. Serum calcium, phosphorus, ALP, PTH and arterial blood pH and bicarbonate were measured during treatment with histamine H2-receptor antagonists accompanied by calcium carbonate in sixteen patients undergoing maintenance hemodialysis. Seven patients receiving histamine H2-receptor antagonists without calcium carbonate were selected as controls. In the sixteen patients receiving calcium carbonate, serum calcium, ALP, PTH and arterial blood pH and bicarbonate were not significantly altered during treatment with histamine H2-receptor antagonists, but serum phosphorus levels increased significantly after four (5.6 +/- 1.1 mg/dl) and eight weeks (5.9 +/- 0.8 mg/dl) of treatment as compared with that before treatment (4.8 +/- 1.2 mg/dl). Furthermore, serum phosphorus levels decreased significantly eight weeks after the discontinuation of treatment with histamine H2-receptor antagonists. In the seven control patients there were no statistical differences in serum calcium and phosphorus levels measured before and after treatment with histamine H2-receptor antagonists. In seven other patients receiving histamine H2-receptor antagonists with calcium carbonate, calcium carbonate was replaced with calcium lactate as the phosphate binder after four weeks of treatment with histamine H2-receptor antagonists. With the 4-week administration of histamine H2-receptor antagonists accompanied by calcium carbonate, the serum phosphorus level increased, similarly to that of the first study (from 6.3 +/- 0.9 to 7.1 +/- 0.5 mg/dl). However, with the substitution of calcium lactate, the serum phosphorus level decreased significantly (6.3 +/- 0.2 and 6.0 +/- 0.9 mg/dl after four and eight weeks, respectively, despite continued administration of histamine H2-receptor antagonists). These results suggest that histamine H2-receptor antagonists significantly affect the phosphorus binding ability of calcium carbonate, but not of calcium lactate. Although the exact mechanism remains obscure, one possible explanation may be related to the rise in pH of the gastric juice. Careful observation of changes in the serum phosphorus level is required in hemodialysis patients receiving calcium carbonate and histamine H2-receptor antagonists. Calcium lactate may be useful as a phosphate binder in such hemodialysis patients.

Adult↗

Adrenomedullin: a new hypotensive peptide.

PROPERTIES OF ADRENOMEDULLIN: We have identified a novel hypotensive peptide, adrenomedullin, in human pheochromocytoma extract. It has potent and long-lasting vasodilatory effects in several vascular systems. In addition to adrenomedullin, another hypotensive peptide, proadrenomedullin-derived peptide (PAMP), was also found to be processed from the adrenomedullin precursor. PAMP inhibits neural transmission at peripheral sympathetic nerve endings, although adrenomedullin directly dilates vascular smooth muscle. POSSIBLE INVOLVEMENT IN PATHOGENESIS: Although initially isolated from human pheochromocytoma tissue, adrenomedullin messenger RNA is highly expressed in several peripheral organs, including cardiovascular tissues. Adrenomedullin and PAMP are both synthesized and secreted from vascular smooth muscle and endothelial cells, and they participate in circulation control through different mechanisms. Taken together with the presence of adrenomedullin-specific receptors on vascular smooth muscle cells and the significant increase in plasma immunoreactive adrenomedullin levels in patients with hypertension, renal failure and congestive heart failure, adrenomedullin may be involved in the pathogenesis of these diseases.

Adrenomedullin↗

Adrenomedullin-immunoreactive neurons in the paraventricular and supraoptic nuclei of the rat.

The existence of adrenomedullin (AM) in the rat hypothalamus was examined by immunohistochemistry. AM-immunoreactive neurons were found in the supraoptic nucleus (SON) and in the magnocellular parts of the paraventricular nucleus (PVN). The co-existence of AM-, oxytocin- and/or vasopressin-immunoreactivity was identified in the same neurons in the hypothalamus. The results suggest that the AM may play a role in neurotransmission or in cardiovascular control with neurohypophyseal hormones.

Adrenomedullin↗

A new type soluble guanylyl cyclase, which contains a kinase-like domain: its structure and expression.

A new type soluble guanylyl cyclase, designated as ksGC (kinase-like domain containing soluble guanylyl cyclase), was identified from a kidney cDNA library. By Northern blot analysis, expression of this novel guanylyl cyclase mRNA was found in lung, kidney and skeletal muscle. Although ksGC is a soluble type guanylyl cyclase, it is not a member of soluble alpha or beta guanylyl cyclases. The ksGC contains in its N-terminal region a protein kinase-like domain, which is usually a characteristic feature only of particulate type guanylyl cyclases. This unique feature of ksGC suggests a novel pathway of cGMP synthesis.

Amino Acid Sequence↗

Three-dimensional dimer structure of the lambda-Cro repressor in solution as determined by heteronuclear multidimensional NMR.

The 1H, 15N and 13C magnetic resonances of the lambda-Cro repressor have been assigned almost completely, mainly through the use of heteronuclear multidimensional NMR methods. Inter-subunit NOEs were distinguished by means of heteronuclear spectral editing technique (13C double half filter technique). Based on the distance and dihedral angle constraints derived from the NMR data, the three-dimensional solution structure of the lambda-Cro repressor in the dimeric form has been calculated by the simulated annealing method. The input for the structure calculations consisted of 1H-1H distance constraints, of which 1536 were intra-subunit and 40 were inter-subunit, and dihedral angle, phi, constraints, which numbered 92. The average root-mean-square deviation (RMSD) for all backbone heavy- atoms of the 20 calculated structures for residues 3 to 59 of the total of 66 amino acid residues in both subunits was 1.57 Angstrum, while the average RMSD for each subunit in the same residue range was 0.66 Angstrum. The subunit is composed of three alpha-helices, residues 7 to 13, 16 to 23 and 27 to 36, and a three-stranded anti-parallel beta-sheet composed of residues 3 to 6, 40 to 44 and 50 to 55. The solution structure of the subunit is essentially the same as that in the crystalline form, but the structure of the dimer form in solution differs from that of the dimer unit in the crystalline form. It is suggested that the solution dimer structure is distorted to fit the recognition helices in the major grooves of DNA on complex formation.

Amino Acid Sequence↗

Increased plasma levels of adrenomedullin in patients with heart failure.

OBJECTIVES: To investigate the role of adrenomedullin in the pathophysiology of heart failure, we measured plasma levels of adrenomedullin in patients with heart failure. BACKGROUND: Adrenomedullin is a potent hypotensive peptide newly discovered in pheochromocytoma tissue by monitoring its elevating activity on platelet adenosine 3',5'-cyclic monophosphate (cAMP). A significant level of adrenomedullin has been identified in human plasma. These findings suggest the possibility of adrenomedullin as a new circulating hormone that participates in the regulation of the cardiovascular system. METHODS: Venous blood samples at rest were obtained from patients with heart failure in New York Heart Association functional classes I (n = 15), II (n = 25), III (n = 16) and i.v. (n = 10) and from normal subjects (n = 27). Plasma adrenomedullin levels were determined by our newly developed radioimmunoassay. Other humoral factor levels measured simultaneously included norepinephrine, atrial natriuretic peptide, brain natriuretic peptide, plasma renin activity, aldosterone and cAMP. Left ventricular ejection fraction was measured by echocardiography. In eight patients with severe heart failure, plasma adrenomedullin levels were measured before and after treatment. RESULTS: The mean (+/- SD) plasma level of adrenomedullin in control subjects was 2.52 +/- 0.75 pmol/liter. Plasma levels of adrenomedullin in patients with heart failure were unaffected in those in functional class I (2.85 +/- 0.62 pmol/liter) but tended to be increased in those in class II (3.54 +/- 0.82 pmol/liter) and were significantly increased in those in classes III and i.v. (4.78 +/- 1.218 and 8.74 +/- 3.43 pmol/liter, respectively). There was a significant correlation between plasma levels of adrenomedullin and norepinephrine (r = 0.618, p < 0.001), atrial natriuretic peptide (r = 0.696, p < 0.001) and brain natriuretic peptide (r = 0.692, p < 0.001). Left ventricular ejection fraction inversely correlated with plasma adrenomedullin levels (r = 0.485, p < 0.001). Plasma adrenomedullin levels significantly decreased after treatment (from 7.40 +/- 3.40 to 3.98 +/- 1.00 pmol/liter, p < 0.05). CONCLUSIONS: These results suggest that plasma level of adrenomedullin are elevated in heart failure and that an increased plasma volume and an activated sympathetic nervous system in this condition may be related to its synthesis or secretion. Given that adrenomedullin exerts potent cardiovascular effects, increased adrenomedullin may be involved in the defense mechanism against further peripheral vascular resistance elevation in heart failure.

Adrenomedullin↗

Correlation between lipoprotein(a) and aortic valve sclerosis assessed by echocardiography (the JMS Cardiac Echo and Cohort Study).

An elevated serum level of lipoprotein(a) (Lp[a]) may be an independent risk factor for atherosclerotic disease, but the relation of Lp(a) to aortic valve (AV) sclerosis has not been determined. We measured serum concentrations of Lp(a) and investigated their relation to the presence of echocardiographic AV sclerosis in residents of a rural village in Japan. We measured serum Lp(a) levels in 347 men and 437 women aged 35 to 90 years (mean +/- SD: 62 +/- 11 years) who participated in mass screening examinations in Wara village, Gifu, Japan. AV sclerosis was assessed by long- and short-axis 2-dimensional echocardiographic views and continuous-wave Doppler echocardiography. AV sclerosis was graded as follows: 0 = normal AV; 1 = increased echo density; 2 = thickening or calcific deposits > or = 3 mm; and 3 = same as 2 with mildly restricted motion (pressure gradient < 16 mm Hg). Lp(a) levels ranged from < 1 mg/dl to 153 mg/dl. The 25th, 50th, and 75th percentile values were 7, 16, and 28 mg/dl, respectively. Lp(a) levels were significantly higher in women than in men (p < 0.01), and did not increase significantly with age. The prevalence of AV sclerosis (grades 2 and 3) increased significantly with age (p < 0.001). AV sclerosis was present in 65 (36.1%) of 180 subjects with Lp(a) levels > or = 30 mg/dl and in 77 (12.7%) of 604 subjects with Lp(a) levels < 30 mg/dl (p < 0.001). There were no significant differences in the prevalence of AV sclerosis in terms of sex, blood pressure, or levels of total cholesterol, high-density lipoprotein cholesterol, triglycerides, or blood sugar. We conclude that increased serum levels of Lp(a), as well as aging, are closely related to AV sclerosis.

Adult↗

Endotoxin markedly elevates plasma concentration and gene transcription of adrenomedullin in rat.

A marked increase in adrenomedullin (AM) concentration was observed in rat plasma collected after intravenous infusion of lipopolysaccharide (LPS). Plasma immunoreactive (ir-) AM concentration increased already after 1 h exposure to 5 mg/kg of LPS and was elevated to 49.7 +/- 2.3 fmol/ml (mean +/- SEM) at 3 h after injection in contrast to 2.7 +/- 0.3 fmol/ml in saline-injected control rats. Plasma ir-AM level increased in a dose-dependent manner in a range of 0.008 to 5.0 mg/kg of LPS. AM gene transcription in LPS-injected rats was augmented more than 3-fold in ileum, liver, lung, aorta, and 2.4-fold even in skeletal muscle, in which AM was not thought to be produced in myocytes. These results, along with our recent data that AM production in cultured vascular smooth muscle cells (VSMCs) is stimulated with LPS, indicate that AM production is highly augmented in blood vessel, lung and intestine by administration of LPS. Since VSMCs express AM-specific receptors, secreted AM is deduced to actually exert a vasorelaxant effect especially in the endotoxin shock.

Adrenomedullin↗

Peptide-selected T cell lines from myasthenia gravis patients and controls recognize epitopes that are not processed from whole acetylcholine receptor.

To study pathogenic T helper cells in myasthenia gravis (MG) reacting against the acetylcholine receptor (AChR), we have previously selected five CD4+ T cell lines/clones from MG patients (or healthy controls) against full-length recombinant human AChR alpha subunit (alpha 1-437); these can all recognize AChR solubilized from human muscle. Recently, T cells selected with pooled AChR subunit synthetic peptides have shown greater heterogeneity than above. Hoping to validate that, we have characterized three MG and six control T cell lines selected with pooled peptides (averaging 33 residues long) covering the alpha subunit sequence; recurring responses to three particular peptides each showed preferred HLA class II restrictions--p75-115/DR4, p138-167/DR4, and p309-344/DR3 (or DR52a). However, none of three lines from MG patients recognized p138-167--even one from a previous responder to this epitope in full-length alpha 1-437; otherwise they resembled those from controls. Moreover, no peptide-selected line responded significantly to whole AChR, alpha 1-437, or even to shorter polypeptides sharing one terminus with the peptide, suggesting specificity for epitopes not naturally processed by APCs from blood. Of 20 sublines maintained with individual peptides, at least 10 responded to independently synthesized overlapping sequences, but four others depended on contaminants in the original peptides. A single line did recognize one longer polypeptide, but only after tryptic digestion; the processing of this cryptic epitope was evidently the limiting factor here rather than its concentration or the T cell sensitivity. Therefore, while synthetic peptides are essential for mapping epitopes, assessment of the pathogenic MG T cell repertoire requires full-length Ag processed naturally.

Amino Acid Sequence↗

Two novel rat guanylin molecules, guanylin-94 and guanylin-16, do not increase cyclic GMP production in T84 cells.

Guanylin, a 15-amino acid peptide homologue of bacterial heat-stable enterotoxins, is an endogenous activator of guanylate cyclase C (GC-C). We isolated two novel guanylin molecules from rat intestinal mucosa. They contained guanylin-15 at their C-termini and were identified as guanylin-94 and guanylin-16 by amino acid sequencing and mass spectrometry. Guanylin-94 and guanylin-16 in total account for 85% of guanylin molecules in both the small and large intestine, guanylin-15 being a minor component. Rat guanylin-94 and guanylin-16 did not increase cyclic GMP production in T84 cells. Identification of the post-translational processing products of guanylin should provide a better understanding of the biosynthesis of the peptide.

1-Methyl-3-isobutylxanthine↗

Effects of vasoactive substances and cAMP related compounds on adrenomedullin production in cultured vascular smooth muscle cells.

To elucidate the regulation mechanism of adrenomedullin (AM) production in blood vessels, we examined the effects of 30 substances on AM production in cultured rat vascular smooth muscle cells (VSMCs). Forskolin and 8-bromo-cAMP suppressed production and gene transcription of AM. Since VSMC expresses AM receptors coupled with adenylate cyclase, AM production may be regulated by intracellular cAMP concentration. Thrombin, vasoactive intestinal polypeptide and interferon-gamma also inhibited AM production, while angiotensin II, endothelin-1, bradykinin, substance P, adrenaline, phorbol ester and fetal calf serum stimulated AM production in VSMC. These results suggest that AM production is regulated by a variety of substances, indicating complex systems regulating AM production.

8-Bromo Cyclic Adenosine Monophosphate↗