Biomedical subjects

A Moers

Publications and source records attributed to A Moers.

5 recordsLinked to original sources

PubMed2005

Platelets in atherothrombosis: lessons from mouse models.

Platelets play a central role in hemostasis and thrombosis but also in the initiation of atherosclerosis, making platelet receptors and their intracellular signaling pathways important molecular targets for antithrombotic and anti-inflammatory therapy. Historically, much of the knowledge about hemostasis and thrombosis has been derived from patients suffering from bleeding and thrombotic disorders and the identification of the underlying molecular defects. In recent years, the availability of genetically modified mouse strains with defined defects in platelet function and the development of in vivo models to assess platelet-related physiologic and pathophysiologic processes have opened new ways to identify the individual roles and the interplay of platelet proteins in adhesion, activation, aggregation, secretion, and procoagulant activity in vitro and in vivo. This review will summarize key findings made by these approaches and discuss them in the context of human disease.

Animals↗

PubMed2005

Loss of Gq/11 family G proteins in the nervous system causes pituitary somatotroph hypoplasia and dwarfism in mice.

Heterotrimeric G proteins of the Gq/11 family transduce signals from a variety of neurotransmitter and hormone receptors and have therefore been implicated in various functions of the nervous system. Using the Cre/loxP system, we generated mice which lack the genes coding for the alpha subunits of the two main members of the Gq/11 family, gnaq and gna11, selectively in neuronal and glial precursor cells. Mice with defective gnaq and gna11 genes were morphologically normal, but they died shortly after birth. Mice carrying a single gna11 allele survived the early postnatal period but died within 3 to 6 weeks as anorectic dwarfs. In these mice, postnatal proliferation of pituitary somatotroph cells was strongly impaired, and plasma growth hormone (GH) levels were reduced to 15%. Hypothalamic levels of GH-releasing hormone (GHRH), an important stimulator of somatotroph proliferation, were strongly decreased, and exogenous administration of GHRH restored normal proliferation. The hypothalamic effects of ghrelin, a regulator of GHRH production and food intake, were reduced in these mice, suggesting that an impairment of ghrelin receptor signaling might contribute to GHRH deficiency and abnormal eating behavior. Taken together, our findings show that Gq/11 signaling is required for normal hypothalamic function and that impairment of this signaling pathway causes somatotroph hypoplasia, dwarfism, and anorexia.

Alleles↗

PubMed1997

Chylomicrons induce E-selectin and VCAM-1 expression in endothelial cells.

An increased adherence of leukocytes to the vascular endothelium appears to be a crucial event in the development of atherosclerosis. The role of endothelial cell adhesion molecules is gaining increasingly interest in this context. Several studies show an influence of lipoproteins, especially low-density-lipoproteins on adhesion molecule stimulation. The aim of our study was to analyze the atherogenic potential of postprandially elevated serum triglyceride levels by investigating the impact of postprandial lipoproteins (chylomicrons (CH, isolated 4 h after a standard oral lipid load)) on the expression of E-selectin (endothelial leukocyte adhesion molecule-1, ELAM-1) and VCAM-1 (vascular cell adhesion molecule-1). In addition we used chylomicrons that had been incubated with lipoprotein lipase (50 U/ml) for 3 h (CH-LPL). The endotoxin lipopolysaccharide (LPS) served as positive control for adhesion molecule stimulation. Human umbilical vein endothelial cells (HUVEC) were incubated with the samples for 4 h and expression of E-Selectin and VCAM-1 was determined by ELISA. The expression of E-selectin was induced by LPS (530 +/- 64% compared to the basal activity (= 100%)) and by CH (342 +/- 94%); CH-LPL had no effect on E-Selectin expression. VCAM-1 expression was stimulated by LPS (395 +/- 221%) and similarly by CH-LPL (322 +/- 136%) but considerably stronger by CH (1245 +/- 324). In summary, chylomicrons induced an enhancement of the expression of both adhesion molecules, which closely resembled or even exceeded the endotoxin-induced stimulation. Interestingly, this effect was diminished or even reversed after incubation with LPL.

Cells, Cultured↗

PubMed1997

Palmitic acid but not stearic acid inhibits NO-production in endothelial cells.

Several studies showed a diminished production of the endothelium-derived relaxing factor nitric oxide (NO) in the early stage of atherosclerosis. The inhibition of NO-production seems to be mediated by lipoproteins, especially oxidized low-density lipoproteins (ox-LDL). There is some evidence, that the interactions of lipoproteins and NO are associated with the phospholipid fraction of lipoproteins. Since fatty acids have different atherogenic properties-depending on chain length, degree of saturation and steric configuration-, we investigated the effect of fatty acids on endothelial NO-production. Human umbilical vein endothelial cells were incubated with palmitic acid and stearic acid in different concentrations in culture medium enriched with serum albumin for five hours. After that, NO-production was stimulated by calcium-ionophore A23187. NO-production was determined by a bioassay method using RFL-6 cells followed by radioimmunological determination of cGMP. NO-production stimulated by calcium-ionophore A23187(100%) was decreased by palmitic acid (10, 50, 100 microM) to 79 +/- 12%; 63 +/- 10% and 53 +/- 14%. In contrast, incubation with stearic acid (10, 50 and 100 microM) had no effect on A23187-stimulated NO-production (94 +/- 11%; 93 +/- 11%; 104 +/- 15%). Thus, palmitic acid but not stearic acid dose-dependently inhibited NO-release by endothelial cells. These different actions parallel the differing atherogenic potential of the two fatty acids.

Calcimycin↗

PubMed1996

Risk factors for latex allergy in patients with spina bifida.

OBJECTIVE AND METHODS: In order to study risk factors for latex allergy in patients with spina bifida, we investigated 165 patients with spina bifida (mean age 9 years). Besides answering a questionnaire, patients underwent skin-prick testing and determination of specific serum IgE to latex as well as a screening test for specific IgE to environmental allergens. A total of 80 patients (49%) were sensitized to latex according to the presence of specific IgE to latex. RESULTS: Skin-prick tests (SPT) with high ammonia latex milk were performed in 81 of our patients with spina bifida and were positive in 36 patients (46%). Concordance of SPT with specific IgE in serum was good. Nineteen out of 165 patients suffered from a clinically relevant latex allergy: five patients had a history of systemic reactions to latex (e.g. severe bronchospasm, anaphylactic reactions), mostly during surgery. Fourteen patients reported clinical symptoms while inflating a balloon; all these 19 patients were sensitized to latex. Number of operations ranged from one to 26 (mean 5 operations). Concentration of specific IgE to latex in serum correlated well with increasing numbers of operations. Some 32/76 patients (41%) with spina bifida who were sensitized to latex showed an atopic disposition, while 21 out of 81 latex-negative patients (26%) were atopic. Of 300 consecutive sera (mean age of patients 9 years) sent to our laboratory for routine determination of specific IgE, 144 (48%) were positive in terms of specific IgE to environmental allergens, of which 247144 (17%) were sensitized to latex. CONCLUSIONS: From our data we conclude that in order to minimize risk of severe systemic clinical reactions, all patients with spina bifida should be screened for their individual risk of latex allergy to plan preventive measures before operations. Main risk factors for latex allergy seem to be: more than five operations, atopic predisposition, history of clinical symptoms while inflating a balloon, and a sensitization with a CAP-class of > or = 4.

Adolescent↗