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Biomedical subjects

G Siegenthaler

Publications and source records attributed to G Siegenthaler.

At least 73 records · Page 4Linked to original sources
PubMed1987

[Digoxin-like natriuretic factor, raised during normal pregnancy, is increased in pregnancy-induced hypertension and pre-eclampsia].

UNLABELLED: The increase of peripheral resistance in pregnancy induced hypertension (PIH) and in preeclampsia (PE) is not yet explained since previous studies have found that renin-angiotensin-aldosterone system is actually depressed, that adrenergic system is inconstantly stimulated and that vasodilating prostaglandins are inconstantly decreased. In order to get a better insight in the pathogenesis of PIH and PE, we have measured the 24 h urinary excretion of digoxin-like natriuretic factor (DLF) in 15 normotensive pregnant women (NP), in 29 women with PIH and in 6 women with PE under normal salt diet, without treatment. DLF have been measured by radio receptor binding assay. Normal values were established in 14 normotensive non pregnant (NNP). In NP, 24 h urinary excretion of DLF was significantly higher than in NNP (respectively 14.9 +/- 7.5 and 9.5 +/- 2.5 nmol/mmol of creatininuria, p less than 0.01). Comparatively to NP, 24 h urinary excretion of DLF was significantly higher in PIH (31.7 +/- 19 nmol/mmol of creatininuria) and in PE (40.7 +/- 16.3 nmol/mmol of creatininuria). In PIH and PE, there were simultaneously a decrease of plasma renin activity and plasma volume but no difference for plasma catecholamines. IN CONCLUSION: 1. the production of DLF is increased by normal pregnancy; 2. it is increased in PIH and PE in comparison with NP and may explain the increase of peripheral resistance.

Adult↗
PubMed1987

Plasma and skin carriers for natural and synthetic retinoids.

Human skin contains several proteins that could bind the hydrophobic retinoids. One is retinol-binding protein (RBP), the plasma carrier of natural vitamin A, retinol, albumin, and two specific cellular-binding proteins, one for retinol (CRBP) and one for retinoic acid (CRABP). Adequate techniques for the study of these proteins in human skin have been developed; this was considered a necessary step in the understanding of how natural and synthetic retinoids work in the skin. A polyacrylamide gel electrophoresis technique followed by protein immunoblot analysis with an antiserum specific against RBP was developed. This technique allowed study of the binding of several natural and synthetic retinoids on the plasma carrier of natural vitamin A for the first time; it was found that only natural retinoids, including retinoic acid, bind to RBP in vitro; retinoic acid binding was found to induce major conformational changes in the protein. Isotretinoin did not bind to RBP. The technique was then used for the study of RBP in human epidermal and dermal extracts; it showed that RBP degradation with loss of binding properties for retinol occurred within the epidermis; this suggests that retinol supply is decreased within the epidermis, a fact that could be linked to cornification. A polyacrylamide gel electrophoresis binding assay was developed for studying CRBPs and CRABPs in human skin cytosolic extracts. This assay is more specific and more convenient than previous ones for studying tissue extracts. The CRABP was (1) in much higher levels in normal epidermis than in normal dermis, (2) dramatically elevated in psoriatic plaques and in some retinoid-responsive dermatoses, and (3) up modulated by both topical and systemic administration of natural and synthetic retinoids. Such alterations were not observed for CRBP. From these and other observations reviewed herein, it seems that CRABP should be one of the first candidates to be carefully analyzed in the search of the cellular receptor for the mediation of the synthetic retinoids in pharmacologic effects in human skin.

Binding Sites↗
PubMed1987

Receptor-assay for endogenous inhibitors of Na-K ATPase.

It is now accepted that there is an endogenous digitalis-like substance (EDLS), previously called natriuretic factor, present in different mammalian species which participates to the regulation of the sodium balance and at least in some situations, to the genesis of hypertension. The physiological and pathophysiological role of this substance is well recognized. However, its chemical nature remains elusive. Our purpose was to define a receptor assay for this EDLS in order to be able to measure its concentration in urine and blood. To do so, we first prepared a pool of lyophylised urine from salt loaded men. The active material was isolated by Sephadex G25 chromatography. Using the same active fraction, we investigated its biological effects. Series of experiments have demonstrated the various properties of the EDLS: inducing natriuresis when injected into a rat, diminishing short circuit current in toad's bladder and colonic mucosa of rat in in vitro preparations, inhibiting Na-K ATPase activity in isolated toad's bladder cells, binding to ouabain receptors and cross-reacting with different antibodies directed against digoxin. Among these properties, the binding to ouabain receptors offers the unique opportunity to progress in our knowledges of the substance, making possible the calculation of its constant of affinity and the estimation of the molality of the active material contained in a gram of crude extract. Knowing the constant of affinity of the EDLS for its receptor would provide the best identification of the substance as long as we do not know its exact chemical nature.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Cellular retinoic acid- but not cellular retinol-binding protein is elevated in psoriatic plaques.

Cellular retinoid binding proteins are thought to be involved in the molecular action of retinoids, a family of compounds successfully used in the treatment of psoriasis. Therefore, both cellular retinol (CRBP)- and retinoic acid (CRABP)-binding proteins were analyzed in psoriatic skin. Three facts emerged from our study: both CRABP and CRBP are detectable in the skin of psoriatic patients; qualitatively, they both appear similar to the corresponding proteins of normal human skin, in terms of their elution profile and apparent Kd; and quantitatively, only CRABP was found to be 3 times higher in psoriatic plaques as compared to either nonlesional skin of psoriatic patients or the skin of normal subjects. Since psoriatic plaques are particularly responsive to systemic retinoids, specifically to retinoic acid analogues, our results suggest for the first time a link between the levels of CRABP and the responsiveness of a nonneoplastic hyperproliferative tissue to systemic administration of retinoids in the human.

Adult↗
PubMed1986

Therapy with a synthetic retinoid--(Ro 10-1670) etretin--increases the cellular retinoic acid-binding protein in nonlesional psoriatic skin.

Cellular retinol (CRBP)-and retinoic acid (CRABP)-binding proteins were determined in samples of lesional and nonlesional skin of psoriatic patients, before and during oral administration of a synthetic retinoid, Etretin (Ro 10-1670). A 200% increase in CRABP levels, measured by the ability of the protein to bind retinoic acid, was observed in the normal skin during treatment. The CRBP levels were not altered during therapy. The results show that CRBP and CRABP are independently regulated in human skin and suggest that synthetic retinoids may exert their pharmacologic effects by interfering with the regulation of natural retinoic acid receptors.

Acitretin↗
PubMed1986

Skin cellular retinoid-binding proteins and retinoid-responsive dermatoses.

We have previously found an important increase of cellular retinoic acid-binding protein (CRABP) in psoriatic plaques whereas the cellular retinol-binding protein (CRBP) was not elevated compared to normal human skin and nonlesional psoriatic skin. In the present study we analyzed CRABP and CRBP levels in a panel of dermatoses in order to address several questions raised by the above findings. Three observations were made: CRBP showed little or no variations whereas CRABP was either normal (seborrheic keratosis, lichenification, nonlesional psoriatic and nonlesional Darier disease skin) or elevated (psoriatic plaques, lamellar ichthyosis, lesional Darier disease, pityriasis rubra pilaris, keratosis pilaris); high levels of CRABP might indicate a greater sensitivity of the lesions to systemic synthetic retinoids with a carboxyl group in the C15 position, and systemic administration of etretin increased the levels of CRABP but not CRBP. These observations suggest that CRABP might be the receptor for synthetic retinoids in the skin and that its analysis might be useful in monitoring retinoid therapy.

Acitretin↗
PubMed1986

cis-Urocanic acid does not inhibit mitogen induced lymphocyte transformation in man.

Urocanic acid (UCA) is a photoreceptor in the epidermis which absorbs UVB. To elucidate the role of UCA as an immunomodulator in the mechanism of immune suppression which occurs after UV irradiation in human, we studied the effect trans-UCA as well as that of its UV induced cis-isomer (cis-UCA) on mitogen induced lymphocyte transformation and on delayed type responses elicited by intradermal testing of a standardized battery of microbial antigens. No inhibitory effect was seen either in vitro or in vivo. Our negative results, both in vivo and in vitro, suggest that if UCA and UCA photoproducts exert an immunomodulatory effect, their effect should be analysed by a more subtle evaluation of the immune system.

Double-Blind Method↗
PubMed1984

The intermediate filament proteins of rabbit normal epidermal Merkel cells are cytokeratins.

Four hundred Merkel cells (MC) have been studied by double-label immunofluorescence using: (1) a monoclonal antibody which has been previously demonstrated to react with MC and (2) antisera and monoclonal antibodies against the 5 types of intermediate filaments. It was demonstrated that MC did not react with vimentin, desmin, glial acidic fibrillary protein, or neurofilament antisera. A strong staining of MC was observed with 2 antisera and 2 monoclonal antibodies against keratin. The cytokeratin polypeptide pattern of MC is probably similar to that of simple epithelia. These findings attest to the epithelial nature of MC.

Animals↗
PubMed1984

Cellular retinol- and retinoic acid-binding proteins in the epidermis and dermis of normal human skin.

The distribution of cellular retinol- and retinoic acid-binding proteins (CRBP and CRABP) in normal human epidermis and dermis was examined by gel filtration. We showed that CRBP is entirely bound to a lipid-protein aggregate and its free form is obtained through delipidation. The type of homogenization procedure appeared to be important for the recovery of CRBP in human skin. The level of CRABP was about 3.1 pmol/mg protein in the epidermis whereas it was only sporadically detectable in the dermis. In contrast, CRBP was found in both tissues at a concentration of about 1 pmol/mg protein. The difference in CRABP concentrations between epidermis and dermis might have biological and therapeutic implications. Dissociation constants (Kd) of CRABP and CRBP were respectively 2.2 X 10(-7) M and 2.51 X 10(-7) M. This method will facilitate the study of CRABP and CRBP in retinoid- responsive dermatoses and enable us to relate the therapeutic effects of retinoids to the levels of cellular retinoid-binding proteins in the skin.

Adult↗
PubMed1982

[Selection of antibiotics and practice and the clinic].

The multiplicity of antibiotics currently available for the treatment of bacterial infections in outpatients and inpatients has led to considerable confusion and uncertainty in recent years. An attempt is made to establish indications for the use of the various groups of antibiotics, paying due regard to cost as well as other aspects. This means drawing a distinction between the respective needs of out- and inpatients. In treating outpatients, where resistance is less of a problem than in hospitals, use is made principally of oral substances. In the light of current knowledge the vast majority of bacterial infections occurring in ambulatory practice can be optimally treated with pyrimidine-sulfonamide combinations, penicillins, tetracyclines and erythromycin. In contrast, the range of broad-spectrum antibiotics administered in hospitals, for the most part parenterally, in infections of a life-threatening nature or due to organisms exhibiting multiple resistance, is quite different. Most important are the more recent penicillins and cephalosporins and the aminoglycosides. By combining betalactam antibiotics with aminoglycosides and attempt is made to extend the therapeutic spectrum and intensify antibacterial activity. A conclusive judgement on the therapeutic differences between the more recent penicillins and cephalosporins as single-substance therapy or in combination with aminoglycosides is not yet possible at present. There seems good reason, however, to combine the more recent penicillins with aminoglycosides in infections in which enterococci, pseudomonas and anaerobic bacteria are also involved. In infections in which there is a possibility of Klebsiella involvement or in which penicillin allergy or penicillin resistance is present, treatment tends to be a combination of cephalosporins and aminoglycosides.

Aminoglycosides↗
PubMed1982

Fatty acid synthetase in human adipose tissue: purification and characterization.

1. Fatty acid synthetase of abdominal subcutaneous adipose tissue of humans obtained at autopsy was purified 95 times with a final recovery of 10%. 2. The purity of the enzyme was verified by polyacrylamide disc gel electrophoresis and isoelectric point determination. Both techniques revealed only one protein band. 3. The fatty acid synthetase molecular weight was determined by SDS-polyacrylamide disc gel electrophoresis and found to be 500,000. 4. The fatty acid synthetase Km for both NADPH and malonyl-CoA were also determined and were found to be 18 and 28 microM respectively. 5. The presence of an active fatty acid synthetase in human adipose tissue raises the obvious question as to its biological role.

Adipose Tissue↗
PubMed1979

[Diagnosis and therapy in daily practice].

Diagnosis and treatment are two essential elements of medical practice. For obvious reasons, it is often impossible to make a definite diagnosis during the initial work-up. This raises the problem of how extensive diagnostic procedures should be to initiate adequate treatment. It is evident that the professional experience of a physician exerts a great influence on therapeutic measures instituted in the private office or in the hospital. Consequently, in certain instances, treatment may be started without a definite diagnosis. Nevertheless, the axiom "no treatment without prior diagnosis" remains a basic principle of medicine.

Diagnosis↗