Biomedical subjects

Y Ichiki

Publications and source records attributed to Y Ichiki.

At least 37 records · Page 2Linked to original sources

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

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

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

Distribution and characterization of immunoreactive adrenomedullin in porcine tissue, and isolation of adrenomedullin [26-52] and adrenomedullin [34-52] from porcine duodenum.

Using a sensitive radioimmunoassay which recognizes the carboxy-terminal region of porcine adrenomedullin, the distribution of immunoreactive adrenomedullin was widely distributed in porcine tissue, and its concentration was highest in adrenal medulla (126 +/- 32 fmol/mg wet tissue; mean +/- SD). Relatively high concentrations of immunoreactive adrenomedullin were found in the right atrium, lung, duodenum, and pituitary gland. The molecular form of immunoreactive adrenomedullin in all porcine tissues was found to be almost wholly porcine adrenomedullin itself by analysis with reverse-phase high-performance liquid chromatography coupled with radioimmunoassay. Minor molecular forms of immunoreactive adrenomedullin were found in the porcine duodenum. These were isolated and identified as adrenomedullin [26-52] and adrenomedullin [34-52].

Adrenomedullin↗

PubMed1995

Different effects of basic fibroblast growth factor and transforming growth factor-beta on the two platelet-derived growth factor receptors' expression in scleroderma and healthy human dermal fibroblasts.

Previous studies have demonstrated that platelet-derived growth factor (PDGF) alpha receptor expression is up-regulated by transforming growth factor-beta 1 (TGF-beta 1) in scleroderma dermal fibroblasts, but not in healthy control fibroblasts. We asked whether this selective effect in scleroderma cells was TGF-beta 1-specific or a general response by studying responses to other growth factors. In this study, we compared the expression of alpha and beta PDGF receptor subunits (mRNA and protein levels) in these two cell types in response to basic fibroblast growth factor (bFGF) and TGF-beta 1. bFGF coordinately stimulated mRNA levels of alpha and beta receptor subunits in healthy fibroblasts, but did not change PDGF receptor expression in scleroderma fibroblasts. Conversely, and in agreement with previous observations, TGF-beta 1 induced PDGF alpha receptor expression in scleroderma fibroblasts, but not in healthy fibroblasts. PDGF beta receptor mRNA levels were induced to similar degrees by TGF-beta 1 in both cell types. PDGF alpha receptor protein levels correlated directly with mRNA levels, induced by bFGF only in healthy fibroblasts and by TGF-beta 1 only in scleroderma fibroblasts. However, PDGF beta receptor protein levels were not altered by either growth factor in either cell type. Thus, the activated state of scleroderma fibroblasts does not include receptor-signaling pathways to bFGF. This distinct pattern of expression of PDGF alpha receptors in scleroderma fibroblasts suggests a possible role for the coordinately expressed PDGF AA ligand/alpha receptor system in the development of fibrosis.

Blotting, Western↗

PubMed1995

Haemodynamic responses to rat adrenomedullin in anaesthetized spontaneously hypertensive rats.

1. The haemodynamic effects of rat adrenomedullin (AM), a novel hypotensive peptide, were examined in anesthetized 16-18 week old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). 2. An intravenous injection of rat AM dose-dependently reduced the mean blood pressure (MBP) with a concomitant fall in total peripheral resistance index (TPRI) and an increase in cardiac index (CI) in both strains of rats. Percent changes in MBP, TPRI and CI were not different between SHR and WKY. 3. The plasma half-life of rat AM in SHR was similar to that in WKY when it was administered at the dose of 1.0 nmol/kg. 4. These findings indicate that AM has a potent vasorelaxant activity in both SHR and WKY. The haemodynamic responsiveness to exogenous AM and its pharmacokinetics in SHR were comparable with those in WKY.

Adrenomedullin↗

PubMed1995

Plasma concentration of human adrenomedullin in patients on hemodialysis.

To investigate a possible pathophysiological role of human adrenomedullin (AM), we measured the plasma concentration of immunoreactive-AM (ir-AM) in 38 patients with end-stage renal disease (ESRD) on hemodialysis (HD) and 38 healthy subjects (age and sex matched). In addition, plasma ir-AM was characterized by a reverse-phase high performance liquid chromatography. The mean value (+/- SEM) of plasma AM in the patients before HD (10.1 +/- 0.67 fmol/ml) was markedly higher than that in the control group (2.9 +/- 0.13 fmol/ml, p < 0.001), but plasma AM levels were not altered by HD. There was a significant correlation between plasma AM levels and mean blood pressure (MBP) in a group of subjects including both patients before HD and healthy subjects (p < 0.01). In chromatographic study, the major peak of ir-AM in the plasma from patients on HD, as well as healthy subjects, emerged at an elution time identical to that of synthetic AM, indicating that the active form of AM was present in the circulating blood. The secretion of AM seemed to be increased in response to the conditions elicited by ESRD such as hypervolemia and/or hypertension, and reduced renal excretion of the peptide may also contribute to its high plasma level.

Adrenomedullin↗

PubMed1994

Identification and hypotensive activity of proadrenomedullin N-terminal 20 peptide (PAMP).

Proadrenomedullin N-terminal 20 peptide (PAMP) is a candidate for a novel biologically active peptide processed from an adrenomedullin precursor. Using a radioimmunoassay for human PAMP, major and minor immunoreactive PAMPs were purified from porcine adrenal medulla and complete amino acid sequences were determined. The major immunoreactive peptide was PAMP itself with an amidated carboxy terminus. The minor one was determined to be PAMP[5-20]. An intravenous bolus injection of human PAMP in anesthetized rats caused a rapid and strong hypotensive effect in a dose dependent manner. The present data indicate that PAMP is an endogenous biologically active peptide which is processed from adrenomedullin precursor.

Adrenomedullin↗

PubMed1994

Immunoreactive proadrenomedullin N-terminal 20 peptide in human tissue, plasma and urine.

Proadrenomedullin N-terminal 20 peptide (PAMP) is a candidate for a novel biologically active peptide processed from proadrenomedullin. This study clearly demonstrates the existence of PAMP in vivo that had been deduced from analysis of cDNA. To identify PAMP in vivo, we established a radioimmunoassay for PAMP and characterized immunoreactivities in human tissue, plasma and urine. Half maximal inhibition of the assay was observed at 10 fmol/tube. A high concentration of immunoreactive PAMP was found in adrenal medulla (18.4 +/- 8.95 fmol/mg, mean +/- S.D.) and pheochromocytoma tissue (12.3 +/- 9.82 fmol/mg) where the concentrations are comparable to that of adrenomedullin. As determined by three different kinds of chromatography, most of the immunoreactive peptide in pheochromocytoma was eluted at a position exactly identical to that of synthetic PAMP. Further, considerable concentration of immunoreactive PAMP was found in human plasma and urine. The present data indicate that PAMP as well as adrenomedullin is processed from an adrenomedullin precursor.

Adrenomedullin↗

PubMed1994

Ca(2+)-dependent cosecretion of adrenomedullin and catecholamines mediated by nicotinic receptors in bovine cultured adrenal medullary cells.

Bovine cultured adrenal medullary cells (4 x 10(6)) contained 4266.5 +/- 370.0 fmol of immunoreactive adrenomedullin and 373.4 +/- 32.6 nmol of catecholamines. Nicotinic (but not muscarinic) receptors mediated the Ca(2+)-dependent co-secretion of adrenomedullin and catecholamines, with the molar ratio of adrenomedullin/catecholamines secreted into the medium being equal to the ratio stored in the cells. The concentration-response curve of carbachol for adrenomedullin secretion (EC50 42 microM) was similar to that for catecholamine secretion (EC50 63 microM). Reverse phase HPLC analysis showed that immunoreactive adrenomedullins in the cells and secreted into the medium were both eluted exclusively at the position almost identical to synthetic human adrenomedullin[1-52]NH2.

Adrenal Medulla↗

PubMed1994

Immunoreactive adrenomedullin in human plasma.

A specific and sensitive radioimmunoassay for adrenomedullin has been developed. Half-maximal inhibition of binding of radioiodinated adrenomedullin was observed at 4 fmol/tube. The radioimmunoassay recognized the entire adrenomedullin molecule and has little crossreactivity with adrenomedullin fragment peptides. Adrenomedullin-like immunoreactivity was found to circulate in human plasma at considerable concentration (3.3 +/- 0.39 fmol/ml). The immunoreactivity of adrenomedullin was eluted at almost the same position as synthetic adrenomedullin on gel-filtration chromatography and reverse-phase high-performance liquid chromatography, suggesting that circulating adrenomedullin recognized by the present radioimmunoassay is identical or very similar to authentic adrenomedullin. Plasma immunoreactive adrenomedullin significantly increased in patients with hypertension, with a progressive rise proportionate to disease severity.

Adrenomedullin↗

PubMed1994

Complete amino acid sequence of porcine adrenomedullin and cloning of cDNA encoding its precursor.

Porcine adrenomedullin was isolated from adrenal medulla extract and its amino acid sequence was determined. The peptide is identical to human adrenomedullin with a single replacement of Gly for Asn at position 40. The cDNA clone encoding the porcine adrenomedullin precursor was isolated and sequenced. The precursor for adrenomedullin (preproadrenomedullin) is 188 amino acids in length, including the adrenomedullin sequence, followed by a glycine (the amide donor). In addition to adrenomedullin, proadrenomedullin (proAM) contains a candidate for a unique 20-residue peptide, proAM-N20, whose carboxy-terminus may be amidated. By RNA blot analysis, porcine adrenomedullin mRNA was found to be highly expressed in several porcine tissues including lung and kidney as well as adrenal medulla.

Adrenal Medulla↗

PubMed1994

Distribution and characterization of immunoreactive adrenomedullin in human tissue and plasma.

A specific and sensitive radioimmunoassay for human adrenomedullin has been developed and distribution and characterization of immunoreactive adrenomedullin in human tissue were investigated. The radioimmunoassay specifically recognizes its carboxyterminal region and half maximal inhibition of binding of radioiodinated adrenomedullin(40-52)NH2 was observed at 11 fmol/tube. Immunoreactive adrenomedullin was abundant in adrenal medulla (47.7 +/- 26.1 fmol/mg, mean +/- S.D.) and was ubiquitously found in all tissue examined. The mean plasma concentration of adrenomedullin in three normal individuals was 17.2 +/- 6.4 pg/ml (mean +/- S.D.). By analysis with reverse-phase high-performance liquid chromatography coupled with the radioimmunoassay, most immunoreactive adrenomedullin in the adrenal medulla, atrium and lung was found to be adrenomedullin(1-52)NH2.

Adrenal Glands↗

PubMed1993

Hemodynamic effects of a novel hypotensive peptide, human adrenomedullin, in rats.

The hemodynamic effects of human adrenomedullin were investigated in anesthetized Wistar rats. Intravenous administration of adrenomedullin (1.0 nmol/kg) caused a rapid and marked reduction in mean blood pressure associated with a decrease in total peripheral resistance. This reduction in mean blood pressure was closely correlated with the decrease in total peripheral resistance. These findings indicate that human adrenomedullin is a potent vasodilator and may have some role in the regulation of blood pressure.

Adrenomedullin↗

PubMed1993

Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma.

A novel hypotensive peptide was discovered in human pheochromocytoma by monitoring the elevating activity of platelet cAMP. Since this peptide is abundant in normal adrenal medulla as well as in pheochromocytoma tissue arising from adrenal medulla, it was designated "adrenomedullin". The peptide, consisting of 52 amino acids, has one intramolecular disulfide bond and shows slight homology with calcitonin gene related peptide. It was found to elicit a potent and long lasting hypotensive effect. The peptide circulates in blood in a considerable concentration, but it was not found in brain. These data suggest that adrenomedullin is a new hormone participating in blood pressure control. Occurrence of adrenomedullin indicates the possible existence of a novel system for circulation control.

Adrenal Gland Neoplasms↗

PubMed1993

Dimeric form of calcitonin gene-related peptide in the porcine thyroid gland.

In this study we investigated peptides that increase rat platelet cAMP in porcine thyroid gland. Gel filtration of extracts from porcine thyroid gland showed high and low molecular weight activity. Low molecular weight activity contained peptides, including calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI). We isolated a high molecular weight peptide (M. W. 11,000) showing potent activity able to increase rat platelet cAMP in porcine thyroid gland. The peptide's N-terminal sequence was determined to be Ser-X-Asn-Thr-Ala-Thr- by gas phase sequencer analysis, a sequence identical to that of porcine CGRP. The peptide had CGRP immunoreactivity as well as platelet cAMP elevating activity. By gel filtration HPLC, synthetic human CGRP (M. W. 3790) was eluted in a position corresponding to M. W. 5,500. These results suggest that judging from its high molecular weight the above peptide is a dimeric form of CGRP.

Amino Acid Sequence↗

PubMed1993

Cutaneous signs (Raynaud's phenomenon, sclerodactylia, and edema of the hands) and hand-arm vibration exposure.

Dermatological tests and examinations of the hand(s) were carried out in vibration-exposed and unexposed males. The subjects were 179 chain-saw workers in private forestry companies and 205 local inhabitants who had never used vibrating tools. The prevalences of Raynaud's phenomenon (RP), sclerodactylia, and edema of the hands were estimated in both groups, and associations between these cutaneous signs and vibration exposure were evaluated. The prevalences of RP and edema in the exposed group were 9.5% and 1.7%, respectively, and in the unexposed group, 2.9% and 1.5%, respectively. Sclerodactylia was seen in 31.8% of the chain-saw workers but in only 6.4% of the unexposed individuals. In statistical analyses based on unconditional logistic regression models with adjustment for age, RP was associated with long-term (> or = 20 years) vibration exposure [odds ratio (OR) = 7.06; 95% confidence interval (CI) = 2.51-19.87]. Sclerodactylia was associated with both short- and long-term vibration exposure (OR = 6.54, CI = 3.30-13.36; OR = 7.05; CI = 3.41-14.60, respectively). There were significant dose-response relationships between RP and duration of exposure and between sclerodactylia and duration of exposure. Results of function tests indicated a longer recovery time and a higher vibration threshold for the workers with RP. The presence of sclerodactylia, however, did not have any significant influence on function test results. It is possible to conclude that not only RP but also sclerodactylia could be induced by vibration exposure. However, most cases of sclerodactylia were not so serious as to involve disturbances of peripheral circulatory and nerve function.

Adult↗

PubMed1993

Pitting scars in progressive systemic sclerosis.

The digital pitting scar is a common clinical feature in patients with progressive systemic sclerosis (PSS). Its pathogenesis is unclear, but it may result in small ulcerations. The clinical and histological features of these lesions are poorly understood. Eighty-seven patients with PSS were examined at least once per year. Pitting scars were defined as pinhole-sized digital concave depressions with hyperkeratosis. They were seen in 34 cases (39%) and were located not only on the tips of the fingers, but also on the sides, especially on the radial border of the index and middle finger and the ulnar side of the thumb, where they had a linear arrangement. Additional pitting scars were noticed on the dorsal surface of the proximal interphalangeal and metacarpophalangeal joints. Pitting was closely associated with several signs of PSS, e.g. Raynaud's phenomenon, skin thickening or articular involvement (e.g. stiffness, swelling, pain). There was no relationship between the number of pitting scars and the duration of PSS. Biopsy samples were taken of the lesions on the lateral sides of fingers in 3 patients. Histologically, there was a plug-like hyperkeratosis with parakeratosis, homogenized collagen fibers and slight perivascular mononuclear cell infiltration. Calcification and altered collagen fibers were observed in the deep dermis. Although pitting scars of the fingertips may be different from those of the lateral sides of the fingers, both histologically and pathogenetically, they were similar clinically. The scar locations on the fingertips and finger joints (proximal interphalangeal and metacarpophalangeal) suggest that exogenous trauma, vibration injury and/or cold exposure may play a role in their pathogenesis.

Adult↗