PubMed Health⌕ Search

Biomedical subjects

T Strasser

Publications and source records attributed to T Strasser.

At least 55 records · Page 3Linked to original sources

The determination of mineralocorticoid receptors in human mononuclear leukocytes from patients with mineralocorticoid excess: physiological and pathological implications.

The affinity and the capacity of mineralocorticoid receptors (MR) in human mononuclear leukocytes (HML) were determined in 9 patients with Conn's syndrome (PA) and in 3 patients with pseudohypoaldosteronism (PHA). The number of binding sites per cell was 136 +/- 39 (mean +/- SD) in PA. One case with PHA had no MR, and of the other 2 patients, one had 50 and the other 55 receptors per cell. The capacity of normal controls ranged from 200 to 400 receptors per cell (n = 20). We conclude that the etiology of PHA is due to a lack of MR in the target tissues and that a down regulation of MR may exist in PA.

Adult↗

The dynamics of blood pressure in populations and hypertensive cohorts.

Two sets of data, derived from the WHO Cooperative Hypertension Community Control Project and concerned with spontaneous changes of blood pressure over a period of five years, are described. The first deals with the community as a whole, studied through the examination of two independent random samples of the same population made five years apart. The second pertains to cohorts of hypertensive subjects included in the hypertension registers from various centres participating in the WHO programme and followed up for four years.The population blood pressure distribution showed a clear shift towards lower levels for both systolic and diastolic values. The mean changes, however, were smaller than 5 mmHg. In the subjects initially labelled as "hypertensive", the effects of "regression to the mean" were apparent both in the short-term evaluation (five months) and, more importantly, after four years of follow-up. In the latter case, the decreases were more remarkable in the first year but continued to show until the third year.These findings suggest that a "controlled" design is necessary not only in prospective clinical trials but also in community projects where the effects of an intervention on blood pressure are to be evaluated.

Adult↗

Studies of atherosclerosis determinants and precursors during childhood and adolescence.

At a Meeting of Investigators on Epidemiological Studies of Atherosclerosis Determinants and Precursors, which was held in Geneva on 7-9 November 1983, representatives from 26 countries reviewed the current status of epidemiological studies in this area. Particular interest was shown in the following determinants of cardiovascular disease: blood pressure, blood lipid levels, body weight, pathological studies, and tobacco use. Working papers on each determinant were prepared, and recommendations were made on areas for research, and on the need for prevention programmes and pathological studies. This article summarizes the work of the meeting.

Adolescent↗

Aldosterone-receptor deficiency in pseudohypoaldosteronism.

Pseudohypoaldosteronism, a syndrome characterized by salt wasting and failure to thrive, usually presents in infancy as high urinary levels of sodium despite hyponatremia, hyperkalemia, hyperreninemia, and elevated aldosterone levels. We have investigated this syndrome for the possibility of abnormal Type I or "mineralocorticoid-like" receptors, which have intrinsic steroid specificity indistinguishable from that of renal mineralocorticoid receptors and are found in many tissues and cells, including mononuclear leukocytes. We have studied three patients with pseudohypoaldosteronism: the 28-year-old index case in Melbourne (Patient 1) and two siblings in Munich, eight and two years of age (Patients 2 and 3); clinically, Patient 3 had a less severe case than his sister. Percoll-separated control monocytes bound [3H]aldosterone with high affinity (Kd approximately 3 nM) and limited capacity (150 to 600 sites per cell). On repeated examination, no [3H]aldosterone binding was found in monocytes from Patients 1 and 2; in Patient 3, the levels were 62 sites per cell, more than 2 S.D. below those of the control. Levels in the parents of the Munich patients (first cousins) were normal. It appears that pseudohypoaldosteronism is caused by a Type I receptor defect, that the defect may be complete or partial, that transmission may be autosomal recessive, and that the study of patients with pseudohypoaldosteronism may indicate physiologic roles for Type I receptors in nonepithelial tissues.

Adult↗

Inhibition of leukotriene B4 formation in human neutrophils after oral nafazatrom (Bay g 6575).

Three grams of nafazatrom (Bay g 6575), given orally to healthy male volunteers in a single dose, significantly reduce the formation of leukotriene B4 in polymorphonuclear leukocytes. LTB4 synthesis fell from 57.1 +/- 17.0 ng/10(7) PMNL, mean +/- S.D., in control to 34.3 +/- 14.4 ng/10(7) PMNL 3 hr after nafazatrom (2 P less than 0.001). In vitro, nafazatrom inhibited LTB4 formation in human PMNL in a dose dependent manner. At 1 microM nafazatrom LTB4 formation was reduced to 65% of the control value. Nafazatrom had no effect on the excretion of 2,3-dinor-6-keto-PGF1 alpha and 2,3-dinor-TXB2, the major urinary metabolites of endogenously synthesized PGI2 and TXA2, respectively. Serum levels of TXB2 in clotted whole blood also remained unchanged. The inhibitory effect of nafazatrom on leukotriene biosynthesis in human PMNL suggests a therapeutic potential of this drug in processes like allergy and chronic inflammation, where leukotrienes play a pathogenetic role.

Administration, Oral↗

Parallel determination of glucocorticoid receptors in human mononuclear and polymorphonuclear leukocytes after Percoll separation.

Circulating human leukocytes are known to possess glucocorticoid receptors, but the data in the literature on the affinity and capacity widely range. We here report our results on the determination of affinity and capacity of glucocorticoid receptors in both mononuclear and polymorphonuclear leukocytes using a Percoll gradient for separating cells. The mean affinity of mononuclear and polymorphonuclear cells was respectively 4.3 +/- 0.7 and 4.3 +/- 15 nM (mean +/- S.D., n = 6), and the capacity 4135 +/- 1950 and 1810 +/- 832 sites per cell. Previous reports using a Ficoll separation showed a lower affinity under the same conditions of incubation. From these findings we suggest that the separation with Percoll may give values closer to physiological than other separation techniques.

Cell Separation↗

Hypertension control in Europe.

Hypertension control is a complex process with many facets; it is dependent upon many factors, e.g., local culture, economic factors, and organization of health care. Examples from the practice of hypertension control in Europe are quoted to illustrate various levels of such activities, their scope, and the methods used. Different operational approaches are illustrated with a number of locally appropriate solutions. Measures of program effect, such as changes in population blood pressure levels, awareness and treatment status of hypertension, drug consumption, and morbidity and mortality statistics, are also examined. Finally, some special issues are summed up: the community problem of "mild" hypertension, sex differences in achieving hypertension control, and partial "overtreatment" (unwarranted drug therapy) in the community. More data are needed on the quality of hypertension control in the populations of Europe.

Blood Pressure↗

Cost-effective control of rheumatic fever in the community.

Rheumatic fever is declining rapidly in importance in the developed countries, but is still a major public health problem in the developing countries. Primary prevention techniques, consisting of the detection and antibiotic treatment of streptococcal infections of the pharynx, are both feasible and effective, but are also costly, as only 10-20% of all pharyngeal infections are due to the beta-hemolytic Streptococcus, and only a small proportion of those actually develop into rheumatic heart disease. A different concerted approach, which is both effective and economically entirely justifiable, is to use antibiotics as a prophylaxis to prevent secondary infection, i.e. relapses of rheumatic fever. A multi-centre study conducted by the WHO has shown that the cost of antibiotics used for secondary prevention was less than the savings resulting from the lower incidence and shorter hospital stays of recurrencies of rheumatic fever. Given economic restrictions, therefore, priority is given to organized and systematic secondary prevention.

Community Health Services↗

Polymorphonuclear leukocyte 5-lipoxygenase activity in psoriasis.

5-lipoxygenase-derived products of arachidonic acid are implicated in the pathophysiology of psoriasis, a common hyperproliferative and inflammatory skin disease. We therefore examined whether there is an activation of this enzymatic pathway in extracutaneous tissues. For this purpose, we measured the conversion of 14C-arachidonic acid by polymorphonuclear leukocytes from psoriatic patients and controls. No significant difference in the generation of leukotriene B4 and 5-hydroxyeicosatetraenoic acid by polymorphonuclear leukocytes was noted between the two groups. We conclude that in psoriasis there is no enhanced activity of the 5-lipoxygenase pathway in circulating polymorphonuclear leukocytes.

Adult↗

Leukotriene B5 is formed in human neutrophils after dietary supplementation with icosapentaenoic acid.

Incorporation and conversion of icosapentaenoic acid (20:5, n - 3) by human polymorphonuclear leukocytes were studied in volunteers (n = 6) ingesting a normal Western diet supplemented with icosapentaenoic acid (approximately equal to 4 g daily). Ingestion of icosapentaenoic acid leads to formation of biologically less active leukotriene B5 (LTB5) from polymorphonuclear leukocytes (PMNL) stimulated with ionophore A23187. LTB5 was identified on HPLC by UV absorption and by GC/MS and showed a behavior identical to that of in vitro synthesized LTB5 produced by incubation of human PMNL with icosapentaenoic acid. The ratio of icosapentaenoic acid/arachidonic acid (20:4, n - 6) in cellular phospholipids increased from 0.045 during control to 0.28 after the supplemented period. LTB5 increased from undetectable values to 70.2 +/- 18.7 pmol of LTB5 per 10(7) PMNL during the experimental period. Synthesis of LTB4 did not change significantly (control, 218.8 +/- 89.1; icosapentaenoic acid-enriched diet, 253.6 +/- 18.7 pmol per 10(7) PMNL). The ratio of LTB4/LTB5 corresponded to the ratio of arachidonic acid/icosapentaenoic acid in PMNL phospholipids. Our findings prove that LTB5, which is 10 to 30 times less potent than LTB4 to cause aggregation, chemotaxis, and degranulation of PMNL, can be formed in vivo in man after dietary icosapentaenoic acid. This may modify the contribution of leukotrienes in processes in which these metabolites are of pathogenetic relevance.

Adult↗

Characterization of aldosterone binding sites in circulating human mononuclear leukocytes.

Aldosterone binding sites in human mononuclear leukocytes were characterized after separation of cells from blood by a Percoll gradient. After washing and resuspension in RPMI-1640 medium, cells were incubated at 37 degrees C for 1 h with different concentrations of [3H]aldosterone plus a 100-fold concentration of RU-26988 (11 alpha, 17 alpha-dihydroxy-17 beta-propynylandrost-1,4,6-trien-3-one), with or without an excess of unlabeled aldosterone. Aldosterone binds to a single class of receptors with an affinity of 2.7 +/- 0.5 nM (means +/- SD, n = 14) and a capacity of 290 +/- 108 sites/cell (n = 14). The specificity data show a hierarchy of affinity of desoxycorticosterone = corticosterone = aldosterone greater than hydrocortisone greater than dexamethasone. The results indicate that mononuclear leukocytes could be useful for studying the physiological significance of these mineralocorticoid receptors and their regulation in humans.

Aldosterone↗

Mineralocorticoid and glucocorticoid receptors in circulating mononuclear leukocytes of patients with primary hyperaldosteronism.

Mineralocorticoid and glucocorticoid receptors were measured in circulating mononuclear leukocytes in 5 patients affected by Conn's syndrome (3 cases of bilateral adrenal hyperplasia and 2 cases of adenoma plus unilateral hyperplasia). The number of the binding sites per cell resulted significantly lower (189 +/- 114, mean +/- SD), as compared with the normal controls (298 +/- 105). The affinity of aldosterone for the receptor was found to be not different than that of healthy control subjects. The capacity and the affinity of dexamethasone for glucocorticoid receptors ranged in the normal values. These data suggest a possible down-regulation of mineralocorticoid receptors in humans.

Adenoma↗

Binding of agonists and antagonists to mineralocorticoid receptors in human peripheral mononuclear leucocytes.

The binding of agonists (liquorice derivatives) and antagonists (spironolactones and cyproheptadine) to Type I aldosterone binding sites was evaluated in human mononuclear leucocytes and compared with data previously obtained using kidney cytosol or kidney slices from adrenalectomized rats. The affinity of spironolactones (spironolactone and canrenone) is equivalent in all the preparations. In contrast, carbenoxolone and glycyrrhizic acid show no affinity for aldosterone binding sites in mononuclear leucocytes, but bind to receptors in kidney cytosol. The possible explanation of the discrepancies is that, in cytosolic preparations, the two latter compounds may undergo hydrolysis into glycyrrhetinic acid which does possess a measurable affinity for mineralocorticoid receptors in all the preparations.

Adrenalectomy↗

Uptake, release and metabolism of docosahexaenoic acid (DHA, c22:6 omega 3) in human platelets and neutrophils.

Exogenous DHA is converted by human platelets to 14- and 11- HDHE and by human neutrophils mainly to 7- HDHE . Human platelets prelabeled with 14C-DHA, 14C-EPA and 14C-AA and stimulated with thrombin release and metabolize DHA only in trace amounts as compared to EPA and AA. 14C-DHA is incorporated into the 2-position of platelet phospholipids and occurs predominantly in phosphatidylethanolamine. DHA and EPA were also incorporated by dietary means into phospholipids of platelets and neutrophils. In resting platelets free DHA as well as free AA and EPA are not detectable. In platelets stimulated ex vivo with thrombin DHA is not significantly released which is in contrast to EPA and AA. After stimulation, 14- HDHE is found only in trace amounts as compared to 12-HETE and 12- HEPE . In DHA enriched neutrophils formation of HDHEs cannot be demonstrated after stimulation with ionophore A 23187. We conclude that even after dietary enrichment of DHA in phospholipids of platelets and neutrophils the level of free DHA and/or formation of HDHEs might be too low to substantially affect arachidonic acid metabolism and related functions of these cells.

Adult↗

[Dietary lipids and serum lipids in adolescents, based on the Geneva study of the precursors of atherosclerosis].

The relationship between serum lipids and nutrition, physical activity and body mass index were studies with a multifactorial analysis of variance in a group of 160 adolescents of both sexes (Table I). These relationships are complex and difficult to demonstrate; they give rise, however, to certain considerations of presumptive characteristics possibly linked with adolescence.

Adolescent↗