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Biomedical subjects

F Marumo

Publications and source records attributed to F Marumo.

At least 469 records · Page 26Linked to original sources

Synthesis and release of endothelin-1 by human decidual cells.

We have studied whether a novel vasoconstrictor, endothelin-1 (ET-1), is synthesized by and released from human decidual cells in early pregnancy, and whether ET-1 acts directly on their own cells. It was observed that ET-1-like immunoreactivity (ET-1-LI) was released from cultured decidual, but not villous, cells, as a function of time. Reverse-phase high-pressure liquid chromatography of the conditioned media from the decidual cells revealed a major peak of ET-1-LI coeluting with standard ET-1. Phorbol myristate acetate, a protein kinase C activator, dose-dependently increased the release of ET-1-LI from the decidual cells, while a protein kinase C inhibitor, H7, significantly attenuated the stimulatory effect of phorbol myristate acetate on ET-1-LI release. Northern blot analysis demonstrated the expression of messenger RNA for prepro-ET-1 in the decidual tissue, but no such messenger RNA was observed in the villous tissue. The human decidual tissue contained a noninteracting, single class of binding sites demonstrating higher affinity for ET-1 and ET-2 than ET-3. This would be most consistent with the ETA receptor subtype. An ET-1-induced, dose-dependent accumulation of total inositol phosphates was also observed in human decidual cells prelabeled with myo-[3H]inositol. The present results demonstrate for the first time that human decidual cells in early pregnancy can synthesize and release ET-1. These cells also possess specific functional receptors for ET-1 which are coupled to phosphoinositide hydrolysis. Thus our data suggest a possible role for ET-1 in autocrine and/or paracrine function in human decidual cells.

Binding, Competitive↗

Hibernating myocardium associated with coronary artery dissection and vasospastic angina.

Hibernating myocardium is an uncommon clinical state involving persistently impaired myocardial function. A 61-year-old man was admitted because of vasospastic angina. Coronary angiography revealed coronary artery dissection in the midportion of the right coronary artery, and segmental vasoconstriction was evoked by acetylcholine. In this patient, hibernating myocardium in the dissected region was clearly demonstrated by dipyridamole thallium-201 imaging. This report describes the first documented case of hibernating myocardium associated with coronary artery dissection, and the usefulness of dipyridamole thallium-201 imaging in the assessment of this state. Coronary artery spasm might be relevant to the etiology of coronary artery dissection.

Aortic Dissection↗

Degradation and distribution of brain natriuretic peptide in porcine tissues.

Brain natriuretic peptide (BNP) is a novel peptide that has actions similar to atrial natriuretic peptide (ANP). The present study investigated BNP localization in the heart, ANP and BNP contents in several organs, and ANP and BNP clearance through these organs. In the morphological study, it was shown that porcine BNP-like immunoreactivity was mainly distributed in the granules of the atrium. The content of porcine BNP-like immunoreactivity in the atrium was extremely high, about 100-fold greater than in the ventricle. From the determination of porcine BNP and ANP contents of such organs as the heart, kidney and liver and also plasma, it was shown that porcine BNP concentration was approximately one order of magnitude lower than that of ANP, and clearance rates of ANP and porcine BNP from these organs were similar and not significantly different between the organs. These results suggest that the modes of secretion and degradation of porcine BNP are not the same as those of ANP.

Animals↗

Direct effect of endothelin-1 on the granuloma cells of the porcine ovary.

Specific binding sites for endothelin-1 (ET-1), a novel potent vasoconstrictor peptide, as well as the effects of ET-1 on cytosolic free Ca2+ concentration ([Ca2+]i), intracellular total inositol phosphate (IP) generation and steroidogenesis were studied in cultured porcine granulosa cells. Scatchard analysis of a binding study using 125I-labelled ET-1 indicated the presence of a single class of high-affinity binding sites with almost equal affinity for ET-1 and ET-3: the apparent dissociation constant was 0.59 nmol/l and the maximal binding capacity was 1.84 pmol/mg protein. Affinity-labelling of 125I-labelled ET-1 to the membranes using disuccinimidyl tartarate as a cross-linker revealed one major and one minor band with the apparent molecular weights of 32 kDa and 49 kDa respectively. ET-1 dose-dependently (1-100 nmol/l) induced rapid and transient increases in [Ca2+]i in fura-2-labelled cells. ET-1 also dose-dependently stimulated total IPs in cells prelabelled with myo-[3H]inositol. ET-1 had a slight stimulatory effect on the secretion of progesterone but not of oestradiol from porcine granulosa cells. The present data clearly demonstrate the presence of a non-selective ET receptor (ETB) in porcine granulosa cells coupled with phosphoinositide hydrolysis and [Ca2+]i mobilization, and suggest that ET-1 may play some role in the production of progesterone by porcine granulosa cells.

Animals↗

A new variant of alpha-1-antitrypsin deficiency (Siiyama) associated with pulmonary emphysema.

A 38-year-old male with pulmonary emphysema due to severely reduced serum alpha-1-antitrypsin (AAT) level (14.5 mg/dl) was found to have an inherited new AAT deficient variant Siiyama. Chest roentgenogram and CT scanning revealed advanced emphysema, and severe obstructive ventilatory impairment was observed. During the 4-year follow-up period, the annual rate of decline of FEV 1.0 showed approximately 10-fold greater than the normal decline in FEV 1.0 (-380 ml/yr). Treatment with tamoxifen in order to raise the serum AAT level only resulted in an insufficient increase. Augmentation therapy of human AAT should be considered in the future.

Adult↗

Effects of caffeine on paracetamol activation in rat and mouse liver microsomes.

1. The effects of caffeine on the NADPH-dependent production of paracetamol-glutathione conjugate were studied in rat and mouse liver microsomes. 2. In the presence of caffeine, glutathione conjugate production in rat microsomes was enhanced, whereas that in mouse microsomes was not affected significantly, showing an apparent species difference. 3. The data partly explain the species difference in the effects of caffeine on paracetamol hepatotoxicity.

Acetaminophen↗

The role of endothelin-1 in the origin of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

Plasma and cerebrospinal fluid (CSF) endothelin (ET)-1-like immunoactivity in 27 patients with aneurysmal subarachnoid hemorrhage (SAH) was measured serially by radioimmunoassay for 2 weeks after SAH onset. Mean ET-1-like immunoactivity levels in plasma of patients with SAH were highly elevated during the whole study period, while the levels in CSF of the same patients were not. Plasma ET-1-like immunoactivity levels in patients with SAH classified as Fisher computerized tomography (CT) Group 3 were higher than those in patients with SAH classified as Fisher CT Groups 1 and 2. There were no significant differences in plasma ET-1-like immunoactivity levels between the patient groups stratified by Hunt and Kosnik grade. In this series, plasma ET-1-like immunoactivity levels in the 12 patients with vasospasm were higher than those in the 15 patients without vasospasm during the 1st week; CSF ET-1-like immunoactivity levels in patients with vasospasm were in the normal range on Days 0 to 3 after SAH onset, then became elevated on Days 5 to 7 and remained high until the end of the 2nd week. In contrast, CSF ET-1-like immunoactivity levels in patients without vasospasm were within the normal range during the entire period of study. The time course of the occurrence of vasospasm and that of the increase in CSF ET-1-like immunoactivity coincided precisely. The possible role of endogenous ET-1 in the pathogenesis of vasospasm due to SAH is discussed.

Adult↗

[Endothelin, EDRF, CGRP].

Endothelin-1 is now known to synthesized in the kidney and influence the renal function. ET-1 mRNA was detected in glomerulus and inner medullary collecting ducts using RT-PCR technique. ETA receptor mRNA was detected only in glomerulus, vasa recta bundle, and arcuate artery. ETB receptor mRNA distributed mainly in glomerulus and collecting ducts. Endothelium derived relaxing factor (EDRF) was believed to be nitric oxide, was synthesized by nitric oxide (NO) synthase from L-arginine. NO stimulates soluble guanylate cyclase and increases cGMP level. NO synthase mRNA was detected in glomerulus and inner medulla. Soluble guanylate cyclase mRNA distributed widely along the nephron segments. NO and cGMP system seems to play some roles in modulating renal functions.

Amino Acid Oxidoreductases↗

Enhanced fibrinolytic activity during the course of hemodialysis.

In order to clarify the effect of hemodialysis (HD) on the fibrinolytic system, fibrinolytic activity was evaluated in 27 patients undergoing regular hemodialysis treatment (RDT) using new parameters including plasma alpha 2-plasmin inhibitor (alpha 2 PI), alpha 2-plasmin inhibitor-plasmin complex (alpha 2 PIC), cross-linked fibrin degradation products (XL-FDP), tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor-1 (PAI-1) antigen. Predialysis baseline levels of plasminogen and alpha 2PI activity in RDT patients were significantly lower and those of alpha 2PIC were significantly higher than normal control values. During a single HD session, alpha 2PIC exhibited a continuous, significant increase reaching about 180% of initial values by the end of HD. alpha 2PI activity was significantly decreased at the end of the HD, though there were no significant changes in plasminogen activity during HD. Predialysis baseline levels of XL-FDP in RDT patients were significantly higher than normal control values. No significant changes in XL-FDP were observed during HD. Both t-PA activity and t-PA antigen significantly increased during HD, and PAI-1 antigen significantly decreased during HD. Von Willebrand factor (vWF) antigen in plasma, which is regarded as reflecting a release reaction by vascular endothelial cells to certain stimuli, also significantly increased during HD. However, neither vWF antigen nor t-PA antigen was increased by heparin administration alone. The changes in alpha 2PI and alpha 2PIC levels suggest that fibrinolytic activity is slightly higher in RDT patients and is even higher during HD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Circulating and excreted forms of atrial natriuretic peptide in healthy subjects and patients with renal diseases.

The immunoreactivity of plasma and urine atrial natriuretic peptide (ANP) was measured in patients with renal disease and in healthy volunteers. The molecular forms of ANP in these subjects were estimated by gel permeation chromatography and reverse phase high performance liquid chromatography. No significant increase in plasma ANP was observed in patients with nephrotic syndrome or non-oliguric chronic renal failure compared to healthy volunteers. However, plasma ANP levels were significantly increased in patients on hemodialysis (normal 18.6 +/- 11.4 fmol/ml; hemodialysis 91.2 +/- 69.9 fmol/ml, p < 0.01). Chromatographic analyses revealed that plasma ANP consisted of only alpha-ANP or combined alpha- and gamma-ANP in healthy volunteers and in nephrotic patients, whereas beta-ANP frequently appeared in the plasma of both dialyzed and non-dialyzed chronic renal failure patients. Excreted forms, except in subjects free from renal disease where gamma-ANP may serve as a potential marker of glomerular injury in humans.

Adult↗

[Urinary acidification].

Current understanding of the features and mechanisms of renal acidification along the nephron segments is summarized. Emphasis is placed on recent approaches to the "structure and function" of H/HCO3 transport proteins by molecular techniques. The amount of renal acidification is strictly matched to the endogenous production of non-volantile acids. This regulation is handled by many factors, including blood acid-base parameters, aldosteron, distal delivery of Na and accompanying anions, extracellular fluid volume, and PTH. Cellular mechanisms of these regulatory factors are summarized.

Acid-Base Equilibrium↗

Reliability of Doppler echocardiographic stroke volume measurement.

To evaluate the accuracy and utility of the echocardiographic Doppler method of determining the stroke volume, the stroke volume was measured in 64 instances in 15 patients and compared to the simultaneous thermodilution stroke volume determinations. Stroke volume, varied by atrial pacing at various heart rates, was calculated noninvasively by the product of the cross-sectional area of the aortic orifice determined by echocardiography and the flow velocity integral measured by continuous wave Doppler. While the cardiac output was increased moderately by atrial pacing, the stroke volume was decreased in relation to the increase in the heart rate. The stroke volume calculated by the echo-Doppler method exhibited a significant linear relationship to the stroke volume determined by thermodilution (r = 0.84) and to the cardiac output (r = 0.75, p less than 0.01). Inter-observer and intra-observer variability was 7 +/- 4% and 5 +/- 4%, respectively. The noninvasive echo-Doppler method of estimating the stroke volume is concluded to be accurate, specifically, to be comparable to the values obtained by thermodilution and with a low inter- and intra-observer variability.

Adult↗

Long-term effects of steroid treatment on nephrotic syndrome associated with Kimura's disease and a review of the literature.

A 68-year-old Japanese male (Case 1) and a 59-year-old Japanese male immigrant to Brazil (Case 2) who suffered from subcutaneous eosinophilic lymphoid granuloma (Kimura's disease) of several years duration, developed nephrotic syndrome. Renal biopsy demonstrated membranous nephropathy in Case 1 and minimal-change lesion in Case 2. Both patients were treated with prednisolone for several months. There was complete remission of nephrotic syndrome in eight years in Case 1 and in three months in Case 2. Proteinuria did not reappear after remission of nephrotic syndrome in either case. In contrast subcutaneous tumors subsided in both cases during steroid treatment but again became active immediately following discontinuation of the drug. These clinical observations suggest that, though some common factor(s) might mediate the development of both skin and renal lesions, the mechanism of action on these two target organs may differ, perhaps serving only as a "trigger" for the initiating mechanism of renal disease.

Aged↗