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Healthy Control Population (healthy + control_population)

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Medical Sciences	100%

Selected Abstracts

Heightened levels of circulating 20S proteasome in critically ill patients

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2005
G. A. Roth
Abstract Background, Recently, circulating proteasome core particles (20S proteasome) have been suggested as a marker of cell damage and immunological activity in autoimmune diseases. Aberrant leucocyte activation and increased lymphocyte apoptosis with consecutive T-cell unresponsiveness is deemed to play a pivotal role in the sepsis syndrome. Moreover sepsis-induced muscle proteolysis mainly reflects ubiqutin proteasome-dependent protein degradation. We therefore sought to investigate serum levels of 20S proteasome in critical ill patients. Material and methods, Case,control-study at a university hospital intensive care unit; 15 patients recruited within 24,48 h of diagnosis of sepsis, 13 trauma patients recruited within 24 h of admission to the ICU, a control group of 15 patients who underwent abdominal surgery, and 15 healthy volunteers. ELISA was used to measure the concentration of 20S proteasome in the sera of the patients and controls. Data are given as mean ± SEM. Mann,Whitney U -test was used to calculate significance and a P -value of 0·05 was considered to be statistically significant. Results, Marked increase of 20S proteasome was detected in the sera of septic patients (33 551 ± 10 034 ng mL,1) as well as in trauma patients (29 669 ± 5750 ng mL,1). In contrast, significantly lower concentrations were found in the abdominal surgery group (4661 ± 1767 ng mL,1) and in the healthy control population (2157 ± 273 ng mL,1). Conclusion, Detection of 20S proteasome may represent a novel marker of immunological activity and muscle degradation in sepsis and trauma patients, and may be useful in monitoring the clinical effect of proteasome-inhibitors. [source]

A Haplotype of the DRD1 Gene Is Associated With Alcohol Dependence

ALCOHOLISM, Issue 4 2008
P. Batel
Background:, The D1 dopamine receptor has been involved in a number of brain functions, including motor control, inattentive symptoms and reward and reinforcement mechanisms. Indeed, DRD1 antagonists may reduce cocaine-seeking behavior and the acquisition of cocaine-cue associations. The D1.1/r4532 marker of the DRD1 gene has been associated with a large set of phenotypes including addictive behaviors, but none with alcohol dependence per se. Methods:, We analyzed a population of 134 patients with alcohol dependence, also assessing more homogeneous (severe) phenotypes, comparing this sample with a healthy control population, assessing two SNPs within the DRD1 gene in order to depict the role of DRD1 polymorphisms and haplotypes. Results:, The T allele of the rs686 polymorphism within DRD1 gene was significantly more frequent in patients with alcohol dependence (p = 0.0008), with a larger excess for patients with severe dependence (p = 6 × 10,6), and even more for patients with severe complications such as withdrawal seizures (p = 7 × 10,7). A specific haplotype rs686*T-rs4532*G within the DRD1 gene was significantly more precisely associated with alcohol dependence in our sample (p = 5 × 10,6). Conclusions:, Even though chance finding cannot be ruled out, convergent evidence is given that the DRD1 gene is a susceptibility gene in alcohol dependence, regarding the fact that relying on more homogeneous phenotypes (i.e., more severe patients) and more informative genetic markers (i.e., haplotypes) reinforce the initial association. [source]

MDM2 SNP309 genotype influences survival of metastatic but not of localized neuroblastoma,

PEDIATRIC BLOOD & CANCER, Issue 4 2009
Chiara Perfumo PhD
Abstract Background MDM2 is a major negative regulator of p53 function and is directly regulated by MYCN in neuroblastoma (NB) cells. MDM2 SNP309, a T-to-G substitution in the MDM2 promoter associated with higher gene expression compared to wild-type, may attenuate the p53 pathway in NB, in which p53 mutations are rare. We investigated its impact on NB development and survival in relation with major clinical and biological characteristics. Procedure A consecutive cohort of 497 NB children, diagnosed in Italy between 1995 and 2005, and a healthy control population of 471 adults were genotyped for MDM2 SNP309. NB patients were followed up until June 30, 2008. Results Patients and controls showed similar distribution of MDM2 SNP309 genotypes. In patients, the polymorphism was not associated with any characteristic at diagnosis. In localized stages no effect of the polymorphism on survival was evident. In stage 4 patients overall survival (OS), event free survival (EFS) and survival after relapse (SAR) were significantly poorer for TG/GG than for TT patients (P,=,0.008; P,=,0.013; P,=,0.046, respectively). In this group, such an effect was more evident in patients with MYCN amplification (OS: P,<,0.001; EFS: P,=,0.028; SAR: P,<,0.001). Conclusions While MDM2 SNP309 status does not affect the risk of developing NB nor disease outcome for localized cancer cases, it significantly correlates with survival in stage 4 NB patients, particularly in the presence of MYCN amplification. The impact of small molecule inhibitors of MDM2 activity in the management of such patients could be usefully considered. Pediatr Blood Cancer 2009;53:576,583. © 2009 Wiley-Liss, Inc. [source]

3123: Non-invasive measurement of retinal oxygenation: principles and expectations

ACTA OPHTHALMOLOGICA, Issue 2010
M HAMMER
Purpose To determine oxygen saturation (SO2) of blood inside retinal vessels which is an essential measure for the estimation of oxygen supply to the tissue as well as its oxygen consumption. Methods Two-, four-, and multiple - wavelength approaches to the non-invasive measurement of SO2 will be discussed. The dual wavelength technique, imaging the fundus at 548 and 610 nm, showed to be most appropriate for clinical routine investigations. The SO2 of the hemoglobin in retinal arterioles and venules is calculated from the ratio of the optical densities of the vessels at both wavelengths. Results From a healthy control population, mean arterial and venous SO2 were measured to be 98±10.1% and 65±11.7% with reproducibility of 2.52% and 3.25% respectively. In a cohort of 41 patients (mean age: 65±12.3 years) with diabetic retinopathy (DR), we found an increase of the venous SO2 with the severity of DR: Mild non-proliferative DR 69±7%, moderate non-proliferative DR 70±5%, severe non-proliferative DR, 75±5%, and proliferative DR 75±8%. Measurements of SO2 in accordance with vessel diameters revealed a correlation of the venous SO2 with arterial as well as venous diameters in 159 diabetic patients (mean age: 55.8±13.9 years) with no or non , proliferative DR. Increased venous SO2 is an indicator of insufficient oxygen supply to the retinal tissue. The correlation of the vessel diameters with venous SO2 may point to compensatory mechanisms of retinal blood flow regulation. Conclusion Accurate retinal vessel oximetry is possible by non , invasive optical methods. Combined with measurements characterising the retinal blood flow, it is a powerful tool for the estimation of retinal oxygen supply and consumption. Commercial interest [source]