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Biomedical subjects

T Eto

Publications and source records attributed to T Eto.

At least 145 records · Page 8Linked to original sources
PubMed1997

The effect of hypothermic cardiopulmonary bypass on plasma adrenomedullin in adult cardiac surgical patients.

Cardiopulmonary bypass (CPB) can evoke a systemic inflammatory response, which is accompanied by an increase in plasma cytokines that may stimulate the production of adrenomedullin (AM), a potent vasodilator peptide. This study was undertaken to investigate whether CPB influenced plasma AM concentration in 10 patients undergoing cardiac surgical procedures. We found that the plasma AM concentration increased significantly after the commencement of CPB, with the greatest increase observed at weaning from bypass (P < 0.01). After CPB, plasma AM concentration declined but still exceeded baseline significantly 24 h postoperatively. The increase in the plasma AM concentration at weaning from CPB correlated significantly with aortic cross-clamp time (r = 0.74, P < 0.05). The authors conclude that the secretion of AM into circulation is augmented by CPB in patients undergoing cardiac surgery, which suggests a possible role of AM in cardiovascular regulation during and after surgery with CPB.

Adrenergic beta-Agonists↗
PubMed1997

Adrenomedullin--physiological regulator of the cardiovascular system or biochemical curiosity?

Adrenomedullin is a potent vasodilator peptide that exerts major effects on cardiovascular function. Adrenomedullin is biosynthesized in a wide variety of organs and cells, although it was initially isolated from human pheochromocytoma tissue. In addition to adrenomedullin, proadrenomedullin N-terminal 20 peptide was found to be processed from adrenomedullin precursor. Both adrenomedullin and proadrenomedullin N-terminal 20 peptide show hypotensive effects in anesthetized rats, but exhibit different hypotensive mechanisms. Further, adrenomedullin possesses multiple biological effects involved in cardiovascular homeostasis. Plasma adrenomedullin concentration is increased in patients with cardiovascular diseases such as hypertension, congestive heart failure, renal failure and septic shock. The present review summarizes the recent advancement of adrenomedullin research and demonstrates that adrenomedullin is one of the important vasoactive peptides involved in the physiology and pathophysiology of circulatory control and control of body fluid.

Adrenomedullin↗
PubMed1997

Hypotensive effect of chronically infused adrenomedullin in conscious Wistar-Kyoto and spontaneously hypertensive rats.

1. The hypotensive effect of chronically infused human adrenomedullin (hAM), a potent vasodilator peptide that has been reported to have a natriuretic action, was examined in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Conscious WKY rats and SHR were infused with 200 ng/h synthetic hAM for 14 days by means of osmotic minipumps. Control groups were infused at the same schedule with 0.9% saline. Systolic blood pressure (SBP) and daily urinary excretion of Na+ and K+ were measured before and during the infusion period. In addition, plasma renin activity (PRA), aldosterone and hAM concentrations were measured on day 14 of infusion. 3. A significant reduction in SBP was observed in hAM-treated SHR at day 2 and SBP remained significantly lower throughout the experiment compared with control SHR. Similarly, SBP in the hAM-treated WKY rats was found to be significantly lower than in control WKY rats during infusion. However, the hypotensive effect was not accompanied by any significant increase in urinary volume or Na+ excretion in hAM-treated rats of either strain. Chronic infusion with hAM significantly suppressed PRA and lowered the concentration of plasma aldosterone in WKY rats but not in SHR. The plasma aldosterone in WKY rats and SHR were 0.9 +/- 0.4 and 0.6 +/- 0.2 fmol/mL, respectively. 4. These findings demonstrate that chronically infused hAM has a hypotensive effect in both WKY rats and SHR without an increase in urinary volume or Na+ excretion at a plasma AM concentration within the physiological limit.

Adrenomedullin↗
PubMed1997

Purification of Vibrio cholerae fur and estimation of its intracellular abundance by antibody sandwich enzyme-linked immunosorbent assay.

The Vibrio cholerae fur gene was previously cloned and sequenced. A putative Fur box was identified in the divergent promoters of irgA, a virulence factor of V. cholerae, and irgB, a transcriptional activator of irgA. In this work, V. cholerae Fur was overexpressed in Escherichia coli and purified to approximately 95% homogeneity. The purified protein bound a DNA fragment containing the irgA-irgB promoter in a gel shift assay. The purified protein was used to raise monoclonal and polyclonal antibodies to V. cholerae Fur, and a Fur sandwich enzyme-linked immunosorbent assay was developed to estimate the intracellular abundance of Fur under a variety of growth conditions. The number of Fur molecules per cell during exponential growth was approximately 2,500, which is higher than most measurements for other bacterial repressors but comparable to the intracellular concentration of the leucine-responsive regulatory protein. The number of Fur molecules per cell increased in the late logarithmic and stationary phases. Growth of V. cholerae in low-iron medium did not alter the intracellular abundance of Fur significantly. Growth under microaerophilic conditions resulted in a significant, approximately twofold decrease in the intracellular levels of Fur. The measurements of intracellular Fur abundance indicate that a large amount of this repressor is produced constitutively and that the concentration of Fur in the cell varies by less than a factor of 2 under the conditions studied. We hypothesize that the high constitutive expression of Fur is necessary for its role as an iron-responsive regulator.

Antibodies, Bacterial↗
PubMed1997

Changes in cardiac adrenomedullin concentration in renovascular hypertensive rats.

We assessed changes in tissue and plasma adrenomedullin levels in two-kidney, one-clip renovascular hypertensive rats. Four weeks after clipping, adrenomedullin concentrations were significantly higher in the cardiac ventricles and lower in the left atrium than the respective values in sham-operated rats. The left ventricular adrenomedullin concentration significantly correlated with systolic blood pressure and the degree of cardiac hypertrophy. No difference was noted in the adrenomedullin concentrations of the adrenal gland, aorta, lung, kidneys, or plasma between the two groups. These findings indicate possible involvement of cardiac adrenomedullin in this model of hypertension.

Adrenomedullin↗
PubMed1997

Evaluation of the role of neutrophils in the pathogenesis of acetic acid-induced colitis in mice.

BACKGROUND: Neutrophils are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease, since prominent neutrophil infiltration has been observed in the inflamed colonic mucosa of patients with IBD. However, the role of neutrophils in the pathogenesis of IBD and experimental colitis remains equivocal. The aim of the present study is to clarify the possible role of neutrophils in the progression of acetic acid-induced colitis in mice. METHODS: Using neutropenic mice treated with cyclophosphamide or with an LTB4 receptor antagonist, ONO-4057, the relationship between the severity of macroscopic colonic damage, the extent of myeloperoxidase (MPO) activities in the colonic tissues, and the number of neutrophils in the blood were examined after induction of colitis in mice. RESULTS: Changes of MPO activity in the colonic tissues paralleled well with the severity of the mucosal damage. In spite of a significant reduction in the number of neutrophils in the blood in cyclophosphamide-treated mice, neither the severity of mucosal damage in the colon nor the increase in MPO activities in the colonic tissues was affected 24 h after induction of colitis. Treatment with ONO-4057 significantly suppressed both the severity of mucosal damage in the colon and MPO activities in the colonic tissues in acetic acid-induced colitis in mice. CONCLUSIONS: The present results, obtained using treatment with cyclophosphamide and ONO-4057, show that the severity or the progression of acetic acid-induced colitis in mice was not influenced by a reduction of circulating neutrophils to about 25% of base line.

Acetic Acid↗
PubMed1997

Increased plasma guanylin levels in patients with impaired renal function.

Guanylin, a 15-amino acid peptide, activates intestinal guanylate cyclase C receptor, thereby regulating intestinal fluid and electrolyte transport through the second messenger, cyclic GMP. To examine the role of the kidney in guanylin metabolism, we used a radioimmunoassay (RIA) to measure plasma concentrations of guanylin in 3 groups; normal individuals, patients who had renal disorders with normal or elevated serum creatinine levels (0.4 < Cre < 11.9 mg/dl), and patients who received hemodialysis (HD). The plasma concentration of immunoreactive guanylin in the normal individuals was 32.3 +/- 4.8 fmol/ml. The concentrations in 32 non-HD patients were correlated with their serum creatinine concentrations (r = 0.81, p < 0.0001). In 16 HD patients the plasma concentrations of immunoreactive guanylin before the start of HD were correlated with their dialysis duration (r = 0.63, p < 0.01). The plasma levels of immunoreactive guanylin in HD patients for whom EVAL membranes were used decreased one hour after the start of HD as compared with the prior levels. The plasma levels in HD patients for whom PC membranes were used showed no change. Ten kilodalton guanylin is the main component of guanylin molecules in the plasma and hemofiltrates of HD patients. These findings suggest that the kidney has a major role in the elimination and/or metabolism of guanylin. Uroguanylin, a member of the guanylin family that was recently isolated from human urine, also acts on the guanylate cyclase C receptor. Further studies of guanylin family peptides should provide a better understanding of the physiological roles of the kidney in the control of water and electrolyte balance.

Binding Sites↗
PubMed1997

[Primary pulmonary lymphoma diagnosed from monoclonality of lymphocytes in a transbronchial biopsy specimen].

A 57-year-old man was found on a routine chest X-ray examination to have three infiltrative shadows: two in the right lung field and one in the left. Examination of a transbronchial biopsy specimen revealed infiltration of many small lymphocytes under the bronchial mucosa. In situ hybridization showed that they were monoclonal, and primary pulmonary lymphoma was diagnosed. The patient also had liver cirrhosis, diabetes mellitus, and hypertension. He was treated with a combination of pirarubein, cyclo-phosphamide, vindesine, prednisolone, and etoposide, but the tumors did not shrink. Therefore, as of the time of this writing he was being given only etoposide.

Biopsy↗
PubMed1997

[Pleural B cell lymphoma presenting as paraplegia].

A 54-year-old man felt pain on the right side of his chest. Two months later, paraplegia developed. A chest CT scan revealed a pleural effusion and a mass lesion along the right parietal pleura. The lesion extended directly into the adjacent part of the spinal canal and compressed the spinal cord. Cytologic examination of the pleural effusion revealed atypical lymphoid cells, and examination of a transcutaneous biopsy specimen showed monotonous atypical B lymphocytes. The diagnosis was pleural malignant lymphoma. Chemotherapy induced a partial remission, but 14 months after the first examination he died of central nervous system involvement. Pleural lymphoma can directly compress the spinal cord and cause paraplegia. Early diagnosis and therapy greatly affect the outcome in patients with spinal cord compression.

Humans↗
PubMed1997

[Adrenomedullin and PAMP].

"Adrenomedullin (AM)" is a novel hypotensive peptide which was discovered in human pheochromocytoma by monitoring the elevating activity of platelet cAMP. In addition, a novel 20 residues hypotensive peptide, termed "proadrenomedullin N-terminal 20 peptide" (PAMP) is processed from proadrenomedullin. By RNA blot analysis, AM mRNA was found to be highly expressed in several tissues including ventricle, lung, kidney, aorta and vascular cultured cells as well as in adrenal medulla. Both AM and PAMP shows hypotensive effects in anesthetized rats, but exhibits different hypotensive mechanism. AM possesses multiple biological effects involving in cardiovascular homeostasis. Further, plasma AM as well as PAMP concentrations significantly increased in various cardiovascular diseases including hypertension and congestive heart failure. The present review summarizes the recent advancement of AM research and demonstrated that AM and PAMP are important vasoactive peptides involved in the physiology and pathophysiology of circulation control.

Adrenomedullin↗
PubMed1997

Recurrent syncope induced by left ventricular outflow tract obstruction: demonstration in a patient with hypertrophic obstructive cardiomyopathy.

A 70-year-old man presented with repeated syncope induced by left ventricular outflow tract obstruction. He was referred to us because of repeated syncope with convulsion at rest. During syncope, electrocardiography showed marked ST segment depression with negative T waves in leads I, II, aVL, aVF and V2-V5 but no arrhythmias. Echocardiography revealed asymmetric septal hypertrophy and complete obstruction of the left ventricular outflow tract due to systolic anterior movement of anterior mitral leaflet and concomitant severe mitral regurgitation. During the catheterization study, syncope with convulsion developed repeatedly without antecedent cause, and was associated with a decrease in systemic blood pressure. Simultaneous pressure monitoring of the left ventricle and femoral artery showed a significant pressure gradient (maximum 110 mmHg). During each episode, systemic blood pressure rose spontaneously with the recovery of consciousness over several minutes. He received temporary atrioventricular sequential pacing and underwent successful mitral valve replacement. Four years later, he was doing well.

Aged↗
PubMed1997

Plasma adrenomedullin in cerebrovascular disease: a possible indicator of endothelial injury.

BACKGROUND: Cultured vascular endothelial and smooth muscle cells actively produce adrenomedullin, a novel vasodilator peptide discovered in human pheochromocytoma tissue. This present study was designed to determine whether the plasma level of adrenomedullin is a useful indicator for estimating the degree of endothelial injury in patients with atherosclerotic disease. METHODS: We used a radioimmunoassay to measure plasma adrenomedullin concentrations in 51 patients with chronic cerebrovascular disease (34 infarctions and 17 haemorrhages) and in 10 subjects without symptomatic cerebrovascular disease. We also measured the plasma concentrations of thrombomodulin and endothelin as markers of endothelial injury. The patients were divided into three groups (A, B, and C) on the basis of the number of risk factors for atherosclerosis: hypertension, hyperlipidemia, smoking, low HDL-cholesterol, diabetes mellitus, and hyperuricaemia. Group A (68.7+/-2.7 years) consisted of patients with 0 or 1 risk factors; B (68.3+/-4.2 years) those with 2 risk factors; and C (69.2+/-3.6 years) those with 3 or more risk factors. RESULTS: The plasma concentration of adrenomedullin in these patients showed a significant positive correlation with age (r=0.33, p<0.05), as well as with the plasma concentrations of thrombomodulin (r=0.54, p<0.001) and endothelin (r=0.53, p<0.001). Moreover, the plasma concentrations of adrenomedullin and thrombomodulin (p<0.005 and p<0.02, respectively) tended to be higher in Group B and to be significantly higher in Group C as compared to Group A. Plasma adrenomedullin concentrations did not, however, significantly differ between the infarction and haemorrhage patients. CONCLUSIONS: These findings suggest that the plasma adrenomedullin concentrations reflect the degree of endothelial injury in patients with atherosclerotic disease.

Adrenomedullin↗
PubMed1996

Adrenomedullin-sensitive receptors are preferentially expressed in cultured rat mesangial cells.

By using cultured rat mesangial cells, we compared the effects on cyclic nucleotide levels of adrenomedullin with those of the structurally related peptides, calcitonin gene-related peptide (CGRP) and amylin. Adrenomedullin potently increased cAMP levels 7-fold in a time- and concentration-dependent manner. Its EC50 was 3 x 10(-9) M. CGRP was less potent (2-fold) with an EC50 of 10(-7) M, and amylin had no effect on cAMP levels. All three peptides failed to increase cGMP levels. Treatment of cells with near maximal concentrations of adrenomedullin (10(-7) M) and CGRP (10(-6) M) had no additive effect on cAMP levels. Human adrenomedullin-(22-52)-NH2, a putative adrenomedullin receptor antagonist, inhibited the production of cAMP elicited by adrenomedullin (IC50: 7 x 10(-8) M) and CGRP (IC50: 5 x 10(-8) M). Human CGRP-(8-37), a CGRP receptor antagonist, conversely, reduced the cAMP elevation caused by these peptides with a lower potency (IC50: 10(-6) M for both peptides). This demonstrated that human adrenomedullin-(22-52)-NH2 was a more effective antagonist for adrenomedullin- and CGRP-specific receptors than human CGRP-(8-37). Results suggest that receptors sensitive to adrenomedullin are preferentially expressed in cultured rat mesangial cells. Immunohistochemical study showed almost no immunoreactive adrenomedullin and CGRP, if any, in the cells. Adrenomedullin may regulate mesangial function as either a paracrine or circulating hormone via a cAMP- but not a cGMP-dependent mechanism.

Adrenomedullin↗
PubMed1996

Proadrenomedullin N-terminal 20 peptide is rapidly cleaved by neutral endopeptidase.

Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide which is processed from an adrenomedullin precursor. PAMP is rapidly cleaved by human neutral endopeptidase (NEP), a protease which plays a key role in the degradation of human atrial natriuretic peptide (ANP). A double reciprocal plot indicated that Km of NEP as a substrate of PAMP was 6.1 microM and V(max) was 3.1 mmol/min/mg of NEP. EDTA, phosphoramidon and thiorphan inhibit the proteolysis of PAMP by NEP. NEP cleaves at least 6 peptide bonds in human PAMP; Arg2-Leu3, Glu8-Phe9, Lys12-Trp13, Lys15-Trp16, Trp16-Ala17 and Ala17-Leu18. The present data suggest that NEP may be involved in the circulation control by degrading PAMP as well as ANP.

Adrenomedullin↗
PubMed1996

The changes of the stromal elastotic framework in the growth of peripheral lung adenocarcinomas.

BACKGROUND: Most peripheral lung adenocarcinomas form a characteristic central fibrosis; however, the mechanism of formation has not yet been clarified. METHODS: The stromal elastosis of 176 patients with peripheral lung adenocarcinomas was studied histologically, morphometrically, radiographically, and clinicopathologically. RESULTS: The tumors were classified into two types, according to the histomorphological pattern of the stromal elastosis: (1) a preserved framework composed of a uniformly thick stroma (Type 1; 20 patients) and (2) a disrupted framework in the central fibrosis in which many air spaces were collagenized or collapsed (Type 2; 156 patients). Around the central fibrosis in the Type 2 tumors, replacement growth took the form of a thin-walled, elastic framework. Image analysis disclosed that the elastotic framework had an increased elastic fiber volume (approximately three- to nine-fold, compared with the normal alveolar wall), especially in Type 1 tumors, related to the contraction of the pre-existing alveolar wall. In Type 2 replacement growth, the amount of elastic fibers was slightly increased, which suggested mild reaction of the pre-existing alveolar wall. Radiographically, Type 1 tumors were characterized by a gradual increase of the density without enlargement, while the Type 2 tumors often enlarged within a short period. Recurrence was seen in 54% of the patients with Type 2 tumors, but in none of those with Type 1 tumors. CONCLUSIONS: In the early development of peripheral adenocarcinoma, there is preservation of the elastotic framework (Type 1) of the stroma due to contraction and thickening of the alveolar walls. As the tumors grow, the elastotic framework is disrupted (Type 2), indicating stromal invasion. Based on the clinicopathologic findings and the outcome, Type 1 tumors may be in situ peripheral lung adenocarcinomas.

Adenocarcinoma↗