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Biomedical subjects

T Eto

Publications and source records attributed to T Eto.

At least 181 records · Page 10Linked to original sources
PubMed1996

Distribution and characterization of rat immunoreactive proadrenomedullin N-terminal 20 peptide (PAMP) and the augmented cardiac PAMP in spontaneously hypertensive rat.

Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide processed from an adrenomedullin precursor. In this study, high concentrations of immunoreactive PAMP (ir-PAMP) were detected in rat cardiac atrium and adrenal gland by the radioimmunoassay (RIA) for rat PAMP. The mean plasma concentration of rat ir-PAMP was 3.8 +/- 0.3 fmol/ml. Analysis in atrium, adrenal gland and plasma with high performance liquid chromatographies showed that most ir-PAMP emerged as one major peak at the position exactly identical to that of the authentic rat PAMP. We further investigated the tissue and plasma concentrations of rat ir-PAMP in spontaneously hypertensive rat (SHR) to elucidate the role of PAMP in hypertension. The ir-PAMP concentration in heart tissue of SHR was found to be increased compared with that of the control rat. Especially, the atrial concentration of ir-PAMP of SHR (5.66 +/- 0.78 fmol/mg wet tissue) was significantly higher than that of the control (3.29 +/- 0.22 fmol/mg wet tissue). Cardiac PAMP might have a role for the protection from systemic hypertension.

Adrenal Glands↗
PubMed1996

[Eosinophilic pneumonia presenting as a mass shadow].

A 35-year-old man underwent routine chest roentgenography and a mass shadow was seen in the left lung field. Examination of a transbronchial lung biopsy specimen revealed that many eosinophils had infiltrated under the bronchial mucosa and into the alveolar septum. The total serum IgE concentration was high, and skin tests with Aspergillus antigen and serum precipitating antibodies against Aspergillus were positive. The mass lesion disappeared without any therapy, and a cystic lesion remained. Mediators released from eosinophils were thought to have damaged the lung tissue. We should have administrated corticosteroids as soon as possible.

Adult↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Inhibition of catecholamine synthesis by proadrenomedullin N-terminal 20 peptide in cultured bovine adrenal medullary cells.

In cultured bovine adrenal medullary cells, proadrenomedullin N-terminal 20 peptide (PAMP), at concentrations > or = 3 microM, inhibited carbachol-induced [14C]catecholamine synthesis from [14C]tyrosine. Carbachol-induced activation of tyrosine hydroxylase was also attenuated by PAMP. These results suggest that PAMP is a novel endogenous peptide that regulates catecholamine synthesis via the suppression of its rate-limiting enzyme in adrenal medullary cells.

Adrenal Medulla↗
PubMed1995

Human proadrenomedullin N-terminal 20 peptide in pheochromocytoma and normal adrenal medulla.

Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide found in adrenomedullin precursor. Using a radioimmunoassay for human PAMP, we purified immunoreactive PAMP (ir-PAMP) from human pheochromocytoma and determined its complete amino acid sequence. The major component of PAMP-like immunoreactivity was found to be PAMP [1-20] NH2 with an amino acid sequence identical to that of the deduced amino acid sequence by cDNA analysis. Both ir-PAMP and ir-adrenomedullin were found to be abundant in normal adrenal medulla as well as pheochromocytoma tissue arising from adrenal medulla, and there was a significantly (p < 0.05) positive correlation between ir-adrenomedullin and ir-PAMP concentrations in these tissues. However, the PAMP/adrenomedullin ratio in pheochromocytoma tissues (0.197 +/- 0.013) was significantly (p < 0.005) lower than that in adrenal medullae (0.384 +/- 0.041). The present data indicate that PAMP is biosynthesized from adrenomedullin precursor, but the biosynthesis or metabolism of PAMP in pheochromocytoma may be different from that of normal adrenal medulla.

Adrenal Gland Neoplasms↗
PubMed1995

Receptors for adrenomedullin in human vascular endothelial cells.

Accumulation of the intracellular cyclic AMP (cAMP) was measured in cultured endothelial cells of the human umbilical vein following the incubation with adrenomedullin, a newly discovered hypotensive peptide, to determine the presence of specific receptors for adrenomedullin. Adrenomedullin increased the intracellular cAMP in a dose-dependent fashion in the endothelial cells, and the EC50 value was as low as 10(-9) M. Calcitonin gene-related peptide (CGRP) that has a homology to adrenomedullin in its amino-acid sequence also increased the intracellular cAMP with an EC50 value greater than 10(-7) M. The effect of CGRP was attenuated in the presence of CGRP-(8-37), a CGRP receptor antagonist. However, CGRP-(8-37) had no effect on the cAMP accumulation by adrenomedullin. These findings indicate that the cultured endothelial cells of human umbilical vein possess specific adrenomedullin receptors coupled with the adenylate cyclase activity that may have little affinity with CGRP.

Adrenomedullin↗
PubMed1995

Adrenomedullin stimulates two signal transduction pathways, cAMP accumulation and Ca2+ mobilization, in bovine aortic endothelial cells.

The biological action of adrenomedullin, a novel hypotensive peptide, on bovine aortic endothelial cells, was examined. The specific binding of adrenomedullin to these cells was observed, and adrenomedullin was found to induce intracellular cAMP accumulation in a dose-dependent manner. EC50 for the cAMP accumulation was about 100 times lower than the apparent IC50 for the binding assay. Adrenomedullin also induced increase of intracellular free Ca2+ in endothelial cells in a dose-dependent manner. The Ca2+ response to adrenomedullin was biphasic with an initial transient increase due to the release from thapsigargin-sensitive intracellular Ca2+ storage and a prolonged increase by influx through the ion channel on the plasma membrane. This intracellular free Ca2+ increase resulted from phospholipase C activation and inositol 1,4,5-trisphosphate formation, and seemed to cause nitric oxide synthase activation by monitoring intracellular cGMP accumulation. Both cAMP accumulation and Ca2+ increased responses to adrenomedullin were mediated by cholera toxin-sensitive G protein, but the two signal transduction pathways were independent. Thus, the results suggest that adrenomedullin elicits the hypotensive effect through at least two mechanisms, a direct action on vascular smooth muscle cells to increase intracellular cAMP and an action on endothelial cells to stimulate nitric oxide release, with both leading to vascular relaxation.

Adrenomedullin↗
PubMed1995

Interleukin-1, tumor necrosis factor and lipopolysaccharide additively stimulate production of adrenomedullin in vascular smooth muscle cells.

To elucidate physiological functions of adrenomedullin (AM) secreted from vascular smooth muscle cells (VSMCs), we examined the effect of cytokines, growth factors and related substances on AM production in cultured rat VSMC. Among them, interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha) and TNF-beta, as well as lipopolysaccharide (LPS), markedly augmented production and gene expression of AM. Although maximal stimulation levels of these substances were not greatly different, ED50 values of IL-1s (0.3 ng/ml) were about 1/10 that of TNFs and LPS. AM mRNA levels maximized at 3-6 h after stimulation with IL-1 beta and LPS, while TNF-alpha increased the AM mRNA level up to 48 h. Furthermore, IL-1 alpha, TNF-alpha and LPS additively increased AM production in VSMC. AM production was slightly augmented by fibroblast, epidermal and platelet derived growth factors. These results suggest that AM secreted from VSMC actually exerts a vasorelaxant effect under physiological conditions such as endotoxin shock, atherosclerosis and inflammation.

Adrenomedullin↗
PubMed1995

Immunohistochemical identification of adrenomedullin in human, rat, and porcine tissue.

The histological localization was investigated of adrenomedullin (AM), a novel vasorelaxant peptide originally isolated from human pheochromocytoma. The immunohistological distribution was examined of AM in human, rat, and porcine tissues using a polyclonal antibody to a fragment comprising C-terminal amino acids 40-52 of human adrenomedullin [AM(40-52)NH2]. Almost all of the human pheochromocytoma and normal adrenal medullary cells of all three species were immunostained and found to be intensely positive for AM. Furthermore, AM-immunoreactive cells were present in the pancreatic islets, gastrointestinal neuroendocrine system, anterior pituitary, and choroid plexus with some degree of interspecies heterogeneity. These findings indicate that AM-immunoreactive cells are widely distributed in the endocrine and neuroendocrine system, suggesting that AM plays some important role in the control of systemic and local circulation and also of humoral secretion.

Adrenomedullin↗
PubMed1995

Augmented adrenomedullin concentrations in right ventricle and plasma of experimental pulmonary hypertension.

Adrenomedullin is a strong vasorelaxing peptide discovered in pheochromocytoma tissue. Monocrotaline, a pyrrolizidine alkaloid derived from Crotalaria spectabilis, is known to cause pulmonary hypertension. To test the hypothesis that adrenomedullin plays a role similar to that of atrial natriuretic peptide or brain natriuretic peptide in modulating right ventricular responses to pulmonary hypertension, we have compared concentrations of immunoreactive rat adrenomedullin and adrenomedullin messenger RNA levels in tissues of monocrotaline treated rats with those of control rats. We also measured the effect of pulmonary hypertension on plasma level of the peptide. The concentrations of adrenomedullin immunoreactivity in right ventricle and plasma were significantly higher in monocrotaline treated rats than in control rats. The messenger RNA level of adrenomedullin in right ventricle was also higher in monocrotaline treated rats than in control rats. These results suggest that adrenomedullin participates in the mechanism to counteract the high blood pressure in pulmonary circulation.

Adrenomedullin↗
PubMed1995

Effects of Bestatin on hematopoiesis in long-term human bone marrow cultures.

The effects of Bestatin (Ubenimex, UBX) on normal hematopoiesis were investigated using long-term bone marrow cultures (LTBMC) to determine whether it might enhance hematopoiesis over a long period, as well as induce the release of cytokines. LTBMC were inoculated with 0.1 or 1.0 microgram/ml of UBX at the onset of culture and was added at each weekly medium change. The cellularity and the content of the progenitors in nonadherent layer were examined each week for 5 weeks; those from the adherent layer were examined at week 5. The number of the nucleated mature cells and that of the myeloid progenitors from the nonadherent layer increased significantly (approximately two-fold) following treatment with UBX vs controls. The total number of colonies and the number of myeloid progenitors, but not that of erythroid progenitors, from the adherent layer increased significantly (about 1.5-fold) following treatment with 1.0 microgram/ml UBX. The level of interleukin-6 (IL-6) in the culture supernatants was significantly increased one day after the addition of 1.0 microgram/ml UBX. Findings indicate that UBX stimulated both the production of mature cells and myeloid progenitors on normal hematopoiesis in LTBMC. This was mediated by an indirect action via IL-6 production.

Aminopeptidases↗
PubMed1995

Plasma adrenomedullin in patients with primary aldosteronism.

Adrenomedullin (AM) is a novel hypotensive peptide originally isolated from the pheochromocytoma tissue of humans. To examine the pathophysiological role of AM in primary aldosteronism (PA), the plasma concentration of AM in patients with PA was measured with a specific radioimmunoassay and compared to that in age- and sex-matched healthy normotensive subjects. In addition, the concentrations of AM as well as catecholamines in the plasma from both the adrenal vein and the inferior vena cava (IVC) were measured to determine whether or not the circulating AM in these PA patients is supplied from the adrenal medulla, which contains a much higher concentration of AM than any other human tissue does. The plasma concentration of AM in the PA patients (4.57 +/- 0.32 fmol/mL, n = 6) was significantly (P < .01) higher than that in the healthy subjects (3.06 +/- 0.20 fmol/mL, n = 12). A significant positive correlation (r = 0.62, P < .01) was observed between the mean blood pressure and the plasma AM level. The AM concentration in plasma from the adrenal vein was almost the same level as that from the IVC although the concentrations of both epinephrine and norepinephrine in the adrenal vein were much higher than those in the IVC. Therefore, it seems unlikely that the plasma AM in the PA patients is mainly supplied from the adrenal medulla. Judging from the potent hypotensive activity of AM, the present findings suggest that AM participates in defense mechanisms acting against the elevation of blood pressure in the patients with PA.

Adrenal Glands↗
PubMed1995

Proadrenomedullin N-terminal 20 peptide (PAMP), an endogenous anticholinergic peptide: its exocytotic secretion and inhibition of catecholamine secretion in adrenal medulla.

In cultured bovine adrenal medullary cells, stimulation of nicotinic receptors by carbachol evoked the Ca(2+)-dependent exocytotic cosecretion of proadrenomedullin N-terminal 20 peptide (PAMP) (EC50 = 50.1 microM) and catecholamines (EC50 = 63.0 microM), with the molar ratio of PAMP/catecholamines secreted being equal to the ratio in the cells. Addition of PAMP [1-20]NH2 inhibited carbachol-induced 22Na+ influx via nicotinic receptors (IC50 = 2.5 microM in a noncompetitive manner and thereby reduced carbachol-induced 45Ca2+ influx via voltage-dependent Ca2+ channels (IC50 = 1.0 microM) and catecholamine secretion (IC50 = 1.6 microM). It did not alter high K(+)-induced 45Ca2+ influx via voltage-dependent Ca2+ channels or veratridine-induced 22Na+ influx via voltage-dependent Na+ channels. PAMP seems to be a novel antinicotinic peptide cosecreted with catecholamines by a Ca(2+)-dependent exocytosis in response to nicotinic receptor stimulation.

Adrenal Medulla↗