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Biomedical subjects

T Eto

Publications and source records attributed to T Eto.

At least 199 records · Page 11Linked to original sources

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↗

Effect of lansoprazole on peptic ulcers.

Lansoprazole is the first proton pump inhibitor developed in Japan. We studied the clinical efficacy of lansoprazole 30 mg q.d. on peptic ulcers and the subsequent relapse rates. The endoscopic healing rate of gastric ulcers (n = 86) after 8 weeks of treatment and duodenal ulcers (n = 52) after 6 weeks of treatment were 94.2 and 96.2%, respectively. The endoscopic S2-stage shift rates in gastric and duodenal ulcers were 45.5 and 65.4%, respectively. Factors affecting healing rates of gastric ulcers included colonization by Helicobacter pylori, the size and depth of the ulcers, pretreatment stage, and ulcer history, whereas those factors did not influence healing in duodenal ulcers. The clearance rates of H. pylori after lansoprazole treatment were 54.5% in patients with gastric ulcer and 66.7% in those with duodenal ulcer. The cumulative relapse rates after 1 year with standard maintenance therapy of H2-receptor antagonists (ranitidine, famotidine, and cimetidine) were 15.8% for gastric ulcer and 21.2% for duodenal ulcer. In conclusion, lansoprazole is highly effective in peptic ulcer disease and there are few relapses after treatment. Furthermore, it is suggested that lansoprazole is efficacious against H. pylori at usual clinical doses.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Quantitative analysis of AML1/ETO transcripts in peripheral blood stem cell harvests from patients with t(8;21) acute myelogenous leukaemia.

Peripheral blood stem cells (PBSC) have been used increasingly for haemopoietic reconstitution after marrow-ablative chemotherapy in patients with acute leukaemia because of the possibility that there is a lower risk of leukaemic contamination. We have developed a titration assay using a competitive reverse transcriptase polymerase chain reaction (RT-PCR) which is able to estimate the number of AML1/ETO transcripts so that minimal residual disease (MRD) can be monitored quantitatively in patients with t(8;21) acute myelogenous leukaemia (AML). Using a qualitative RT-PCR method, AML1/ETO transcripts could be detected in all samples from 15 first PBSC harvests and 11 second PBSC harvests obtained from 15 patients with t(8;21) AML. With our competitive RT-PCR assay, the number of AML1/ETO transcripts was found to be lower in the second PBSC harvest than that in the first in every individual. Furthermore, MRD in PBSC harvests was less than that in the corresponding bone marrow obtained on the day of PBSC collection in the individual patients studied. In 10 patients who received autologous blood stem cell transplantation (ABSCT), we could not find a relationship between the number of AML1/ETO transcripts in the infused PBSC harvests and the clinical outcome after ABSCT. The present study clearly indicates that although PBSC harvests collected after consolidation chemotherapy are contaminated by leukaemic cells, the degree of leukaemic contamination may decrease as chemotherapy is repeated. The mobilization of PBSC by repeated chemotherapy may provide an advantageous source of haemopoietic stem cells for ABSCT.

Adolescent↗

Characterization of blasts from a patient with eosinophilic blast crisis of chronic myelogenous leukaemia.

We investigated the biological characteristics of 'eosinophilic' leukaemic blasts from a patient with eosinophilic blast crisis of chronic myelogenous leukaemia (CML). Southern blot analysis of the bcr gene demonstrated the identical single rearranged band in both the leukaemic blasts and mature eosinophils. IL-3, IL-5 and GM-CSF significantly enhanced proliferation and differentiation of these leukaemic blasts, and only eosinophils were generated from in vitro cultures. Those eosinophils expressed the B3A2 chimaeric messenger RNA seen in the leukaemic blasts. These observations indicate that eosinophil progenitors may be involved in the development of eosinophilic blast crisis of CML and that IL-3, IL-5 and GM-CSF act on the leukaemic eosinophil progenitors.

Blast Crisis↗

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↗

Mechanisms of adrenomedullin-induced vasodilation in the rat kidney.

To explore the mechanisms of adrenomedullin-induced vasorelaxation, we tested the effects of adrenomedullin on renal function in rats in vivo and measured the release of endothelium-derived nitric oxide from isolated perfused rat kidney (using a chemiluminescence assay) and the diameters of the glomerular arterioles in the hydronephrotic kidney. Adrenomedullin decreased blood pressure in a dose-dependent manner (3 nmol/kg: -29 +/- 2% [SEM]; P < .01) and slightly increased the glomerular filtration rate and urinary sodium excretion (+108%; P < .05). These changes were associated with significant increases in urinary excretion of cyclic AMP (+54%; P < .05). Adrenomedullin decreased renal vascular resistance (10(-7) mol/L adrenomedullin: -41 +/- 2%; P < .001) and increased release of nitric oxide (+5.1 +/- 0.7 fmol/min per gram kidney weight; P < .001) in the isolated kidney. This increase in nitric oxide release was abolished by the inhibitor NG-monomethyl-L-arginine, and it also reversed the decrease in renal vascular resistance seen with adrenomedullin. Renal responses of deoxycorticosterone acetate-salt hypertensive rats to adrenomedullin were significantly smaller than those of control rats for both release of nitric oxide (10(-7) mol/L adrenomedullin: +0.8 +/- 0.2 fmol/min per gram kidney weight; P < .01 versus control) and renal vasodilation (-28 +/- 6%; P < .05). Videomicroscopic analysis revealed that adrenomedullin increased the diameters of both afferent and efferent arterioles (3 nmol/kg: +11%; P < .05). Thus, adrenomedullin-induced renal vasodilation is partially endothelium dependent and is attenuated in deoxycorticosterone acetate-salt hypertension, probably due to endothelial damage.

Adrenomedullin↗

Calcitonin gene-related peptide mediates acetylcholine-induced endothelium-independent vasodilation in mesenteric resistance blood vessels of the rat.

The role of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves in acetylcholine chloride (ACh)-induced vasodilation was studied in the perfused mesenteric vascular bed isolated from the rat. Bolus infusions of ACh at smaller doses (0.1 and 1 nmol) produced rapid and short-lived vasodilation. However, larger doses (10 and 100 nmol) of ACh caused a rapid and subsequent long-lasting vasodilator response in which the duration of vasodilation was prolonged in a concentration-dependent manner. Pretreatment with capsaicin (1 mumol/L for 20 minutes) significantly shortened the duration of vasodilator response to ACh but did not affect the initial rapid phase of ACh-induced vasodilation. Chemical removal of the vascular endothelium by perfusion with sodium deoxycholate (1.75 to 1.80 mg/mL) for 30 seconds and subsequent treatment with N omega-nitro-L-arginine (100 mumol/L) to inhibit nitric oxide synthesis abolished the initial rapid vasodilator action of ACh at any given concentration. However, in the same preparation, increasing concentrations (from 1 to 1000 nmol) of ACh produced only the long-lasting vasodilator responses in a concentration-dependent manner. This long-lasting vasodilator response to ACh infusion was abolished by capsaicin pretreatment (1 mumol/L), human CGRP[8-37] (CGRP receptor antagonist, 1 mumol/L), and atropine (muscarinic ACh receptor antagonist, 1, 10, and 100 nmol/L) but not by hexamethonium (nicotinic ACh receptor antagonist, 1 and 10 mumol/L). In the preparations without endothelium, the bolus infusion of ACh (300 nmol for 30 seconds) evoked a long-lasting vasodilation and release of CGRP-like immunoreactivities into the perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Exercise-induced secretion of brain natriuretic peptide in essential hypertension and normal subjects.

To determine the major stimuli for the release of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP), we measured their plasma concentrations in 14 normal subjects and 19 patients with essential hypertension during exercise with a bicycle ergometer. The plasma levels of both hormones at baseline were significantly higher in the hypertensive group than in the controls (p < 0.05). The exercise raised both the plasma BNP and ANP, with concomitant increases in systolic blood pressure (SBP), heart rate (HR) and plasma norepinephrine (NE) or epinephrine (Epi) in each group. In the controls the change in ANP correlated with those in SBP, HR and NE (p < 0.05), and similarly the change in BNP with those in SBP, HR, NE and Epi (p < 0.05). In multivariate regression analysis only NE was found to be a significant stimulus for ANP secretion, whereas SBP or Epi was related to BNP release. In the hypertensives the change in ANP correlated with those in HR and NE, but on multivariate regression analysis the change in ANP correlated only with that in HR. The change in BNP in the hypertensives correlated only with that in HR. These findings indicate that in normal subjects the exercise-induced release of BNP and ANP is more sensitive to a similar but slightly different sympathetic stimulus, whereas in hypertensives the major stimulus for the release of both hormones is heart rate, indicating that the mediators for BNP or ANP release are altered by some factors involved in hypertension.

Adult↗

Kidney-limited recurrence in a patient with microscopic polyarteritis.

A 58-year-old woman with kidney-limited recurrence of microscopic polyarteritis (MPA) is described. The patient had a history of histologically-confirmed MPA 7 years previously, which had been in remission with corticosteroid treatment for 30 months followed by no medication thereafter. However, in February 1994, clinical manifestations including leg edema and proteinuria developed, followed by rapidly progressive renal insufficiency. Renal biopsy revealed crescentic glomerulonephritis with necrotizing vasculitis. Furthermore, at the same time antimyeloperoxidase antibody (MPO-ANCA) was detected in plasma. She was diagnosed as having kidney-limited recurrence of MPA without systemic presentation. Corticosteroid therapy was reinstituted, and the renal function improved, with a decrease in the titer of MPO-ANCA.

Acute Kidney Injury↗

Plasma adrenomedullin in various diseases and exercise-induced change in adrenomedullin in healthy subjects.

Adrenomedullin is a novel hypotensive peptide recently discovered in human pheochromocytoma. In the present study, we measured the plasma immunoreactive adrenomedullin of healthy subjects and patients with various diseases. Immunoreactive adrenomedullin was found to circulate in blood of the healthy subjects at a considerable concentration (3.3 +/- 0.3 fmol/ml). Plasma adrenomedullin was significantly increased in the patients with congestive heart failure (5.4 +/- 0.3 fmol/ml), essential hypertension (5.3 +/- 0.4 fmol/ml) and renal disease (4.9 +/- 0.4 fmol/ml). In healthy volunteers physical exercise significantly increased the plasma adrenomedullin concentration. The increase of adrenomedullin was inversely related to systolic blood pressure. These findings indicate that adrenomedullin participates in the circulation control in both physiological and diseased conditions. Although the exact origin of circulating adrenomedullin is still unknown, it is thought to be released rapidly by acute exercise, thereby regulating the cardiovascular system by its vasodilating activity.

Adrenomedullin↗

[Squamous cell carcinoma of the lung with high CT number, but without calcification].

Squamous cell carcinoma of the lung was diagnosed in a 64-year-old man. Chest roentgenographic and tomographic examinations did not show areas of high-density in the tumor, but chest CT scan showed diffuse, scattered, high-density nodules in the tumor. Histologic examination did not show calcification, and calcium staining (Kossa method) was negative. Examination of the thin-slice CT, the soft X-ray film, and the resected slice of the lung indicated that the high-density nodules seen in the tumor on the chest CT scan corresponded to markedly fibrotic lesions with severe anthracosis. This case shows that high-density areas on a CT scan may reflect non-calcified lesions.

Calcinosis↗

[Pulmonary malignant lymphoma associated with bilateral diffuse linear, reticular, and consolidated shadows].

A 72-year-old asymptomatic man was admitted to our hospital with abnormal chest radiographic findings: bilateral diffuse linear, reticular, and consolidated shadows. Malignant lymphoma (diffuse small-cell B-cell lymphoma) was diagnosed histologically after an open lung biopsy and was confirmed by a genetic examination. The lymphoma cells had infiltrated widely in various regions of the lung, including the alveolar spaces and walls, the bronchial and vascular spaces, and the pleura. This diffusion of the lymphoma cells might have accounted for the chest X-ray findings. Malignant pulmonary lymphoma should be included in the differential diagnosis patients with diffuse linear, reticular, and consolidated shadows on chest X-ray films.

Aged↗

Molecular forms of human brain natriuretic peptide (BNP) in plasma of patients on hemodialysis (HD).

Plasma brain natriuretic peptide (BNP) levels have been reported to increase in patients with heart failure and end-stage renal disease (ESRD); however, little is known about molecular forms of plasma BNP that increase in these diseases. In the present study, we analyzed the molecular forms of plasma BNP in ESRD patients of both before (pre-) and after (post-) hemodialysis (HD) state. The plasma extract was analyzed by gel filtration on a TSK-GEL G2000 SW column followed by a RIA for both BNP and atrial natriuretic peptide (ANP). In the pre-HD patients, a 14- to 2300-fold increase in plasma level of immunoreactive (ir-) BNP was observed when compared to normal controls. A ratio of BNP-32 to g-BNP (pro BNP) in plasma from the patients was much larger than that in plasma from normal subjects, indicating that the high plasma level of ir-BNP level in the patients on HD largely results from a marked increase in BNP-32. HD significantly (P < 0.01) lowered the plasma levels of both BNP-32 and g-BNP with a greater reduction in BNP-32 than in g-BNP. Whereas, a-ANP was a main molecular form of plasma ANP in both pre- and post-HD plasma. These results suggest that plasma BNP-32 plays an important role in the sodium-fluid balance and that secretion and metabolism of BNP may differ from those of ANP in the HD patients.

Adult↗

[A case of necrotizing sarcoid granulomatosis].

A 60-year-old woman was admitted to our hospital because of progressive cough and chest pain for 2 months. She also complained of exertional dyspnea. Bilateral diffuse infiltlative shadows were found on the chest roentogenogram. Ground-glass opacity in the middle lobe and lingula, and subpleural patchy consolidation were seen on the computed tomogram of the chest. Arterial oxygenation and diffusing capacity were low. The level of angiotensin-converting enzyme in serum was normal, but that of lysozyme was high. In the BAL (broncho-alveolar lavage) fluid, total cell count and the number of lymphocytes were high, and the CD 4/8 ratio of the lymphocytes was high. Open lung biopsy revealed numerous confluent sarcoid granulomas with necrosis, which strongly correlated with severe vasculitis. After necrotizing sarcoid granulomatosis was diagnosed, prednisolone was administered, which resulted in improvement of symptoms and disappearance of chest-radiograph shadows. Necrotizing sarcoid granulomatosis may be seen as a variant type of sarcoidosis. However, clinical findings including the chest-radiograph shadows and clinical course of this case differ from those of ordinary sarcoidosis. These clinical findings can be attributed to severe vasculitis, as revealed by histological examination.

Female↗

Synchronous circadian rhythms of mRNA levels and activities of cholesterol 7 alpha-hydroxylase in the rabbit and rat.

Cholesterol 7 alpha-hydroxylase, the key enzyme in a series of metabolic changes for the production of bile acids from cholesterol, shows circadian rhythms. The mechanism of the circadian rhythms is the subject of controversy; moreover, few pieces of information are presently available. Because the rabbit is a good animal model for the study of human cholesterol-bile acid metabolism, in the present study we isolated a complete cDNA encoding rabbit cholesterol 7 alpha-hydroxylase (3022 base pairs (bp) long and 1503 bp open-reading frame encoding 501 amino acid residues). Using this isolate rabbit cDNA and the rat cDNA as probes, the circadian rhythms of this enzyme were studied in normal male rabbits and rats. The animals were maintained on a 12-h light-dark cycle. Three subjects each were then killed every 3 h for 1 day. The livers were harvested, and the mRNA levels and the activities of the enzyme were measured. Both mRNA levels and activities of the enzyme showed remarkable circadian rhythms, with higher values during the dark phase and lower values reaching minimum during the light phase. The enzyme activities correlated well with the mRNA levels. There was no shift in the cycles of the enzyme activities and the mRNA levels. These findings suggest that pretranslational regulation is the most likely mechanism for the circadian rhythms of cholesterol 7 alpha-hydroxylase. Because the rhythms of mRNA levels and activities of this enzyme are synchronous, the turnover of the enzyme should be as fast as that of the mRNA, and we can hereafter measure the mRNA levels instead of the enzyme.

Amino Acid Sequence↗

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↗