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M Christ

Publications and source records attributed to M Christ.

At least 91 records · Page 5Linked to original sources
PubMed1992

Aldosterone-specific membrane receptors and rapid non-genomic actions of mineralocorticoids.

Functional studies in extrarenal, non-epithelial cells such as smooth muscle cells and more recently circulating human lymphocytes have provided increasing evidence that aldosterone produces not only classical genomic effects, but also rapid, non-genomic effects on transmembrane electrolyte movements. These involve activation of the sodium/proton exchanger of the cell membrane at very low, physiological concentrations of aldosterone with an acute onset within 1-2 min. A second messenger cascade involved is the inositol 1,4,5-trisphosphate/calcium pathway which responds over the same rapid time course. Such changes clearly cannot be explained by genomic mechanisms, which are responsible for later effects than the membrane related rapid responses. The mechanisms underlying these rapid effects of aldosterone on electrolytes have been extensively studied in human lymphocytes, which thus may represent valuable tools in the delineation of the receptor-effector mechanisms involved. The unique characteristics of this new pathway for steroid action include its rapid time course, 10,000-fold selectivity for aldosterone over cortisol and the ineffectiveness of spironolactones, classical mineralocorticoid antagonists, as antagonists of the response.

Aldosterone↗
PubMed1992

Coronary microcirculation during halothane, enflurane, isoflurane, and adenosine in dogs.

We investigated the effects of clinically administered volatile anesthetics and of adenosine on the microvasculature of the in situ beating canine heart. Thirteen dogs were studied during general anesthesia with an opioid (piritramide), which was infused throughout the experiments. Measurements were obtained in each animal at control (piritramide only) and during hypotension (mean arterial pressure 60 mmHg) induced by halothane, enflurane, isoflurane, and adenosine. Using epiillumination and fluorescence microscopy, 354 arterial microvessels with diameters from 20 to 450 microns were examined through all experimental periods. Hypotension by halothane, enflurane, isoflurane, and adenosine reduced coronary vascular resistance by 13%, 23%, 40%, and 85%, respectively. Coronary venous PO2 was unchanged from control with halothane (+/- 0%) and enflurane (+7%) and significantly increased with isoflurane (+16%) and adenosine (+65%). Left ventricular blood flow decreased significantly during halothane (-35%) and enflurane (-23%); was unchanged from control during isoflurane (-9%); but significantly increased during adenosine (+397%). Coronary arterial and arteriolar diameters increased with all hypotensive agents. Vasodilation was least with halothane, intermediate with enflurane and isoflurane, and most pronounced with adenosine. Diameters increased considerably more in vessels with initial diameters below 100 microns as opposed to larger vessels. Calculation of microvascular segmental resistances revealed that the maximum conductance changes during volatile anesthetics were located in the vessel segments visualized by microscopy, i.e., in vessels larger than 20 microns. However, this was not the case with adenosine. We conclude that volatile anesthetics induce coronary vasodilation by preferentially acting on vessels with diameters from 20 microns to approximately 200 microns, whereas adenosine, in addition, has a pronounced impact on the small precapillary arterioles.

Adenosine↗
PubMed1992

The early mineralocorticoid effector mechanism, the sodium-proton exchanger, is sensitized in lymphocytes from patients with Cushing's syndrome.

OBJECTIVE: In-vitro binding of aldosterone to mineralocorticoid receptors on human mononuclear leucocytes and its effects on the intracellular sodium and potassium concentrations, the sodium-proton exchanger and cell volume of human mononuclear leucocytes have been described for normals. In the present paper this easily accessible human cell model was studied in Cushing's syndrome to detect abnormalities of the mineralocorticoid effector mechanism. DESIGN: The rate of cell swelling in isotonic sodium propionate reflecting the activity of the sodium-proton exchanger and the stimulatory activity of 1.4 nM aldosterone were determined in a Coulter Channelyzer. PATIENTS: Nine female patients with pituitary-dependent (7) and adrenal hypercortisolism (2) were included in the study. MEASUREMENTS: Compared with controls from matched normals, the cell volume of human mononuclear leucocytes in a physiological buffer was significantly increased in the patients. The increment of cell size in isotonic sodium propionate was elevated in the presence of 1.4 nM aldosterone only. RESULTS: These findings are equivalent to an excess stimulation of the sodium-proton exchanger by aldosterone in these patients. Plasma cortisol was inversely correlated with the cell swelling in propionate. CONCLUSIONS: These data indicate that the early mineralocorticoid effector mechanism in human mononuclear leucocytes from patients with Cushing's syndrome has an increased sensitivity to aldosterone compared with that from normals. This could reflect an adaptation of the cellular electrolyte metabolism to the decreased mineralocorticoid activity balancing the increased glucocorticoid activity. If representative of other cell systems, e.g. renal tubular cells, these findings would identify accompanying electrolyte disorders in these patients not as a side-effect of glucocorticoids, but as a result of an increased sensitivity to endogenous mineralocorticoids.

Adolescent↗
PubMed1992

Membrane receptors for aldosterone: a novel pathway for mineralocorticoid action.

Rapid nongenomic in vitro effects of aldosterone on intracellular electrolytes, cell volume, and Na(+)-H+ antiport have been found in human mononuclear leukocytes (HML). Binding of 125I-labeled aldosterone to plasma membranes of HML shares important features with these functional data. This includes a very low apparent dissociation constant (Kd) of 0.1 nM for both aldosterone and the effect on the Na(+)-H(+)-antiport, a high turnover rate, and the almost exclusive binding selectivity for aldosterone. Dexamethasone, RU 26988, corticosterone, ouabain, amiloride, and 18-hydroxyprogesterone were inactive as ligands. Deoxycorticosterone acetate had an intermediate activity with an apparent Kd of 100 nM. These findings are the first to demonstrate membrane binding of aldosterone being compatible with major aspects of its nongenomic effects.

Aldosterone↗
PubMed1992

[ST-segment depressions and spontaneous changes in blood pressure and heart rate in simultaneous 24-hour recording in hypertensive patients].

In 15 patients with essential hypertension (but without coronary heart disease) simultaneous 24-h monitoring of the ST-segment and blood pressure was performed. Twenty-six periods with significant ST-segment depressions were recorded. In 10/26 periods with ST-segment depressions blood pressure was elevated, heart rate was increased in 20/26 ST-segment depressions. During nine periods with ST-segment depressions angina pectoris was reported, and 27 anginal attacks without ST-segment depressions were observed. These data show ischemic episodes in hypertensive patients without coronary heart disease being associated with spontaneous increases of blood pressure and/or heart rate.

Angina Pectoris↗
PubMed1992

Dilation of coronary microvessels by adenosine induced hypotension in dogs.

An experimental model was established for fluorescence video microscopy of coronary microvessels. Nineteen dogs were anesthetized with a narcotic. Catheters were placed for hemodynamic monitoring and sampling of arterial and coronary venous blood. Myocardial perfusion was measured with radioactive microspheres. Following thoracotomy, movements of the myocardial surface area under investigation were restricted by a specially designed heart holder. Plasma was stained with FITC labelled dextran. Diameters were determined in arteriolar and venular microvessels greater than or equal to 20 microns. Measurements were performed during baseline conditions, i.e. only the basic anesthetic drug was applied, and during coronary vasodilation by continuous infusion of adenosine in a randomized sequence. Mean arterial pressure was reduced from 85 +/- 2 mmHg during baseline to 59 +/- 1 mmHg by infusion of 16.9 +/- 2.2 mg.kg-1.h-1 adenosine. Adenosine increased left ventricular blood flow by 253%, left ventricular oxygen demand remained unchanged. A total of 495 arteriolar and 170 venular diameters were measured during baseline condition and during adenosine infusion. Arteriolar diameters increased in all vessel segments between 20 and 600 microns, however, arterioles below a critical size of 100 microns had a greater dilating capacity than larger arterioles. Maximal decrease of segmental resistance occurred in 20-40 microns arterioles and amounted to 74%, which is less than the 82% decrease of total coronary resistance. Venular diameter changes, too, were more pronounced in smaller vessels.

Adenosine↗
PubMed1991

High affinity aldosterone binding to plasma membrane rich fractions from mononuclear leukocytes: is there a membrane receptor for mineralocorticoids?

In vitro effects of aldosterone on the intracellular concentrations of sodium, potassium and calcium, cell volume and the sodium-proton-antiport have been described in intact human mononuclear leukocytes (HML). In the present paper, the binding of a [125I]-labeled aldosterone derivative to plasma membrane rich fractions of HML was studied. High affinity binding of the radioligand with an apparent Kd of approximately 0.1 nM was found. Aldosterone displaced the tracer at a similar Kd. Both canrenone and cortisol were inactive as ligands up to concentrations of 0.1 microM. The findings are the first to demonstrate membrane binding sites with a high affinity for aldosterone, but not for cortisol. These data are perfectly compatible with major properties of steroidal effects on the sodium-proton-antiport in HML and thus very likely represent membrane receptors for aldosterone.

Aldosterone↗
PubMed1991

Left ventricular surface tissue oxygen pressures determined by oxygen sensitive multiwire electrodes in pigs.

STUDY OBJECTIVE: Polarographic oxygen sensitive electrodes can be used to measure tissue oxygen pressures on the surface of the beating heart. The purpose of the study was to clarify the significance of these PO2 determinations. DESIGN: Changes in left ventricular surface oxygen pressures, subendocardial or subepicardial wall functions (ultrasonic dimension technique), and blood flow (radioactive microsphere technique) were correlated during different degrees of acute coronary artery stenoses in pigs. EXPERIMENTAL MATERIAL: 19 anaesthetised open chest pigs, 28-40 kg body weight, were studied during different degrees of constriction of the left anterior descending artery which did not influence overall left ventricular function or irreversibly damage the myocardium. MEASUREMENTS AND MAIN RESULTS: Highly significant (p less than 0.001) correlations (each % delta) were obtained for surface tissue oxygen pressures (y) with subepicardial (y = 0.002 e 0.10x; r = 0.89) and subendocardial (y = 1.44 e 0.04x; r = 0.98) blood flow values, as well as with subendocardial function (y = 82.4 + 0.22x; r = 0.89); a significant correlation was also obtained for subendocardial function (y) with subendocardial blood flow (y = 66.0 + 0.28x; r = 0.69). However, no significant correlation was obtained for polarographic tissue PO2 with subepicardial segment function, indicating that regional function was maintained when tissue PO2 recordings were not much above 0 kPa and when blood flow was reduced by 25 to 30%. CONCLUSIONS: Oxygen pressures of the superficial layers of the left ventricle are relatively high at normal values of oxygen consumption but decrease rapidly if blood supply is reduced. Regional wall function is preserved at low oxygen pressures. Polarographic surface PO2 electrodes hence can be used to study influences of experimental interventions on oxygenation of the normally perfused and of the moderately ischaemic myocardium.

Animals↗
PubMed1990

Epicardial oxygen tensions during changes in arterial PO2 in pigs.

Arterial hypoxemia decreased epicardial tissue PO2, measured by means of a multiwire surface electrode, as well as coronary venous PO2 and myocardial lactate extraction. Left ventricular blood flow increased, O2 delivery, O2 demand and O2 consumption of the left ventricle remained unchanged. Thus, epicardial and coronary venous PO2 indicated decreased capillary and interstitial PO2 rather than cellular hypoxia. A linear relation between mean epicardial PO2 and coronary venous PO2 proves both parameters equally effective in reflecting changes in myocardial tissue oxygenation. However, PO2 distribution curves provide additional information and epicardial PO2 is superior in models with regional changes of myocardial oxygenation.

Animals↗
PubMed1988

Campylobacter pylori gastritis in the acquired immunodeficiency syndrome.

Campylobacter pylori has been associated with gastritis, duodenitis, and duodenal ulceration in the immunocompetent individual. It has been described within the superficial mucus layer, in interepithelial junctions, and occasionally in the microcanaliculi of epithelial cells, but never in the lamina propria. We describe a case of invasive C. pylori in a patient with the acquired immunodeficiency syndrome and discuss its clinical presentation and histopathological findings.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Aziridinylbenzoquinone in recurrent, progressive glioma of the central nervous system. A Phase II study by the Illinois Cancer Council.

Aziridinylbenzoquinone (AZQ) was studied in a Phase II protocol for persons with glioma of the central nervous system (CNS) recurrent or progressive after surgery and radiotherapy. Patients received AZQ, 30 mg/m2 intravenously every 3 weeks if previously untreated or 27.5 mg/m2 if previously exposed to cytotoxic drugs. Partial response was defined as a reduction of at least 50% reduction in the product of the two longest perpendicular diameters of the indicator lesion persisting for a minimum of 28 days. Twenty-eight patients are evaluable for response at this time. Objective response (OR) occurred in four (14.3%): two complete and two partial. Stabilization of disease (SD) was seen in 7 (25.0%). Median survival, in weeks, was greater than 46.0 for responders, 41.7 for SD, and 19.3 for those with progressive disease. The survival experiences are significantly different (P = 0.030 [Breslow]). The OR rate was 21.1% in 19 without prior chemotherapy and 0% in 9 previously treated patients. There were two AZQ-related deaths in patients with prior exposure to nitrosoureas (1 CNS hemorrhage; 1 aspiration pneumonia). One patient had an anaphylactic reaction. Three patients whose tumor initially increased in size subsequently had marked tumor shrinkage. AZQ is an active agent that must be used with added caution in patients who have received nitrosoureas. Initial tumor enlargement may precede response. Although response appears to prolong survival, the correlation between stabilization of disease and survival is not well-defined.

Adolescent↗
PubMed1983

Recurrent squamous cell carcinoma of the skin.

A retrospective analysis of all patients having the diagnosis of squamous cell carcinoma of the skin at a single hospital over a ten-year period was performed. These lesions are less common than both basal cell carcinomas and malignant melanomas. Noninvasive squamous cell carcinomas were not observed to recur. There was a 20% incidence of recurrence in 86 patients with invasive squamous cell carcinoma. The presence of solar changes in the skin did not obviate recurrence. The larger, less differentiated lesions had a greater probability of recurrence. When the depth of invasion of the lesions were determined, it was found that only the lesions that penetrated to Clark's Level IV or V recurred. Squamous cell carcinomas that penetrate to this depth have the potential to recur and metastasize to regional lymph nodes and should be considered malignant lesions, even if they are associated with actinic skin changes.

Aged↗
PubMed1980

[Skin embolisation by drugs (author's transl)].

After intragluteal injection of a drug mixture in a 39-year-old woman, circumscribed necroses developed at the site of injection. This is a rare complication of intramuscular administration of certain drugs, most of them antirheumatic agents. A haemorrhagic dermatitis develops, which may progress to necrosis. Healing occurs after spontaneous or surgical (deep excision) exclusion of the necrotic area with atrophic scarring. The complication is so rare that there is no requirement for the doctor to inform the patient of this possibility before injection. Nor is there liability by the doctor or the nurse who undertake the injections.

Adult↗