Homocysteine effect on protein degradation rates

OBJECTIVES: To show the effect of homocysteine (Hcy) on the degradation rates of proteins. DESIGN AND METHODS: Degradation rates of short-lived proteins in neutrophils were measured in in vivo human model of elevated plasma Hcy and lower vitamin status and in animal model of Hcy added in vitro to rat neutrophils. RESULTS: In the human study, we found significant coefficients of correlation between plasma total homocysteine (tHcy) and the degradation rates of 21 protein fractions. In the animal model, Hcy significantly increased degradation rates of 57 protein fractions. CONCLUSIONS: The increase in protein degradation rates, induced by Hcy, may provide a clue to our understanding of the mechanism of Hcy detrimental effects. Hcy may amplify the specific effect of cellular solutes on protein conformation, thereby monitor protein degradation rates to control enzyme activity. Consequently, the cell may lose its ability to maintain an efficient control of some crucial metabolic pathways, possibly leading to atherogenesis.     

Correlation and overlapping between nuchal translucency and triple test among Down syndrome-affected pregnancies

OBJECTIVES: To examine the correlation and extent of overlapping between first-trimester nuchal translucency (NT) and second-trimester triple test (TT) results in Down syndrome (DS)-affected pregnancies. METHODS: Results of both tests were obtained in 28 cases with DS. Inter-test correlation was performed by comparing the likelihood ratios (LRs). Screen-positive rates (risk >1:380) were calculated for different age groups by adjusting age-dependent background risk and tests' LRs. Overlapping referred to ratio between screen-positive cases by both tests simultaneously and total screen-positive cases by either one or both tests. RESULTS: No correlation was found between the tests' LRs (Pearson correlation test, r = 0.0487). The overlapping between the tests was 25% and 38.5% among young patients of 20 and 35 years of age, respectively. The average overlapping among patients between 25 and 35 years of age was approximately 33%. Only 3 of the 28 DS cases demonstrated LRs <1 by both tests and moreover none exhibited LRs <0.2 by both tests. CONCLUSIONS: The degree of overlapping of one third, between NT and TT, confirms the assumption that both tests utilized together improves DS detection. Screen- negative result, by both tests simultaneously, may reassure low-risk population and aid to reduce the number of non-indicated invasive tests.     

Hospitalized patients' views on in-ward psychological counseling

This qualitative study explores the feelings and beliefs of patients hospitalized in an orthopedic rehabilitation ward for receiving psychological help in that setting. Semi-structured interviews with 10 hospitalized patients were audiotaped, transcribed verbatim, and analyzed using interpretative phenomenological analysis (IPA). Themes of an approach-avoidance conflict towards receiving psychological help were identified, some of them unique to the hospital setting. Approach tendencies were associated with high psychological distress, awareness of free accessibility, and beliefs in body-mind relationship. Avoidance tendencies were associated with fears of psychotherapy, misconceptions, and perceived threats to one's independence and self-esteem. The implications of these findings for the provision of psychological counseling in hospital settings are discussed.     

Graft of choice to right coronary system in left-sided bilateral internal thoracic artery grafting

BACKGROUND: The complementary graft of choice to the right coronary artery system in patients undergoing left-sided bilateral internal thoracic artery grafting has yet to be determined. Saphenous vein graft (SVG) was compared with right gastroepiploic artery (RGEA) as the supplemental conduit to the right coronary artery when left-sided bilateral internal thoracic artery grafting is implemented. METHODS: From April 1996 to July 1999, 234 patients underwent bilateral internal thoracic artery grafting to the left coronary system with RGEA grafted to the posterior descending artery (RGEA group). They were compared with 127 patients with left-sided bilateral internal thoracic artery in whom SVG was used for grafting the right coronary system (SVG group). RESULTS: Female sex (27% versus 14.5%), diabetic patients (40% versus 27%), emergency cases (21% versus 7.3%), and left main coronary artery disease (34% versus 23%) were more prevalent in the SVG group. Number of grafts per patient was higher in the SVG group (3.8 versus 3.5, p = 0.04). Thirty-day mortality was 3.9% in the SVG and 2.6% in the RGEA group (not significant). Occurrence of postoperative complications (myocardial infarctions, strokes, bleeding, and sternal infections) was similar. Return of angina was similar (1.6% versus 3.8% in the SVG and RGEA groups, respectively). Midterm follow-up (4 to 56 months) showed comparable 1-year and 4-year survival (Kaplan-Meier) for both groups (92.8% and 91.7% in the SVG group, and 94.7% and 88% in the RGEA group, respectively). CONCLUSIONS: In patients undergoing left-sided bilateral internal thoracic artery grafting, the use of RGEA for revascularization of the right coronary system does not confer clinical benefits over SVG after midterm follow-up.     

Hyperhomocysteinemia and vitamin score: correlations with silent brain ischemic lesions and brain atrophy

Elevated fasting plasma total homocysteine concentration (tHcy) and lower vitamin status are associated with atherosclerotic states. Silent brain ischemic lesions and brain atrophy, prevailing in the elderly, are affected by tHcy and vitamin status. The study was performed on 56 outpatients who had undergone brain computed tomography (CT) before the onset of the study. According to brain CT evaluation, three groups were set: minor brain ischemia, brain atrophy and control. Brain CT, tHcy, plasma pyridoxal phosphate (PLP), vitamin B(12), folic acid and cognitive and functional capacities were measured or evaluated in all of the subjects. Plasma vitamin score for three vitamins was calculated. In subjects with minor brain ischemic lesions (n = 21), tHcy was higher by 5.6 microM, whereas vitamin score and cognitive function were lower than in controls (n = 24). In subjects with brain atrophy (n = 11), plasma PLP and cognitive function were lower. Particular attention should be paid to tHcy monitoring, vitamin status assessment and brain impairment evaluation.     

c-Cbl is a critical modulator of the Ron tyrosine kinase receptor

Ron, the receptor tyrosine kinase (RTK) for the macrophage stimulating protein (MSP), activates multiple signaling pathways by recruiting several positive regulators to a multifunctional docking site. Here we show that stimulation by MSP also recruits a negative regulator, the c-Cbl ubiquitin ligase, to the multifunctional docking site as well as to a juxtamembrane tyrosine autophosphorylation site. c-Cbl recruitment to these two sites results in polyubiquitylation of Ron molecules, which are subsequently sorted for endocytosis and degradation. Both the phosphotyrosine binding domain of c-Cbl and its RING domain are essential for downregulation of Ron. Although Ron and c-Cbl are found also in physical complexes that include Grb2, these associations are insufficient for productive ubiquitylation of Ron. Our results shed light on the mechanism of receptor desensitization mediated by c-Cbl and its binding partner Grb2.     

The mu opioid agonist DAMGO stimulates cAMP production in SK-N-SH cells through a PLC-PKC-Ca++ pathway

The mu-opioid agonist DAMGO exerts a dual activity on cAMP production in SK-N-SH neuroblastoma cells. While the classic inhibitory effect was prevented by pretreating the cells with pertussis toxin (PTX), the stimulatory activity was PTX-resistant. The stimulatory effect was abolished by the selective phospholipase C (PLC) blocker U-73122, by the selective protein kinase C (PKC) blocker chelerythrine and by the calcium-channels blockers Ni++, Co++ and Cd++. Hence, it is suggested that the opioid receptor activates PLC (probably through Gq GTP-binding proteins), to mobilize PKC, that positively modulates calcium channels in the plasma membrane; the entry of Ca++ into the cells stimulates calcium-activated adenylyl cyclases to produce cAMP.