The screening power of methylenetetrahydrofolate reductase C677T polymorphism versus plasma homocysteine concentration in patients with stenosis of the internal carotid artery

BACKGROUND: Hyperhomocysteinemia is an important and independent risk factor for vascular disease. About 35% of patients with stroke and 47% of patients with peripheral arterial disease have elevated plasma homocysteine (HCY) concentrations. The relationship between plasma HCY and the methylentetrahydrofolate reductase (MTHFR) C677T polymorphism is still unclear, especially in regard to screening/diagnostic power. METHODS: This case-control study was performed on 96 patients, who underwent surgery due to asymptomatic or symptomatic high grade stenosis of the internal carotid artery (ICA), and 96 healthy age and sex-matched, controls. Plasma HCY concentration was determined using a commercial kit for fully automated analysis (AxSYM, Abbott). The C677T polymorphism of the MTHFR-gene was assessed by PCR. RESULTS: The mean plasma HCY concentration was significantly higher in the group with stenosis of ICA compared to the controls, 12.43 ± 6.96 μM and 10.16 ± 3.16 μM, respectively, (p < 0.05). An HCY plasma concentration of 1.5 SD above the mean value of the control group, was defined as cut-off for a pathological versus physiological plasma concentration. The sensitivity and specificity of HCY was 0.27 and 0.94, respectively. The positive predictive value was 0.82. There was no significant difference in the frequency of the MTHFR 677 CT and TT genotype between patients and controls (47% vs. 47% and 8.3% vs. 11.4%, respectively). Carriers of the T-allele (CT and TT genotypes) have significantly higher plasma HCY concentrations than CC patients, 14.1 ± 7.6 μM and 10.29 ± 5.2 μM, respectively, p < 0.05. Sensitivity and specificity of the MTHFR C677T polymorphism (T-allele) were 0.56 and 0.40, respectively. The positive predictive value was 0.48. There was no significant difference in plasma HCY or genotype frequency of the MTHFR C677T polymorphism between asymptomatic and symptomatic patients. CONCLUSION: Our study shows that in a population with a given pretest disease probability of 50%, the determination of plasma HCY concentration, with a positive predictive value of 0.82, is more suitable for screening of patients at risk than analysis of the MTHFR C677T polymorphism

Gene expression in acute Stanford type A dissection: a comparative microarray study

BACKGROUND: We compared gene expression profiles in acutely dissected aorta with those in normal control aorta. MATERIALS AND METHODS: Ascending aorta specimen from patients with an acute Stanford A-dissection were taken during surgery and compared with those from normal ascending aorta from multiorgan donors using the BD Atlas™ Human1.2 Array I, BD Atlas™ Human Cardiovascular Array and the Affymetrix HG-U133A GeneChip(®). For analysis only genes with strong signals of more than 70 percent of the mean signal of all spots on the array were accepted as being expressed. Quantitative real-time polymerase chain reaction (RT-PCR) was used to confirm regulation of expression of a subset of 24 genes known to be involved in aortic structure and function. RESULTS: According to our definition expression profiling of aorta tissue specimens revealed an expression of 19.1% to 23.5% of the genes listed on the arrays. Of those 15.7% to 28.9% were differently expressed in dissected and control aorta specimens. Several genes that encode for extracellular matrix components such as collagen IV α2 and -α5, collagen VI α3, collagen XIV α1, collagen XVIII α1 and elastin were down-regulated in aortic dissection, whereas levels of matrix metalloproteinases-11, -14 and -19 were increased. Some genes coding for cell to cell adhesion, cell to matrix signaling (e.g., polycystin1 and -2), cytoskeleton, as well as several myofibrillar genes (e.g., α-actinin, tropomyosin, gelsolin) were found to be down-regulated. Not surprisingly, some genes associated with chronic inflammation such as interleukin -2, -6 and -8, were up-regulated in dissection. CONCLUSION: Our results demonstrate the complexity of the dissecting process on a molecular level. Genes coding for the integrity and strength of the aortic wall were down-regulated whereas components of inflammatory response were up-regulated. Altered patterns of gene expression indicate a pre-existing structural failure, which is probably a consequence of insufficient remodeling of the aortic wall resulting in further aortic dissection

Геоэкологическая характеристика и элементный состав листьев тополя территории г. Тюмень

Работа направлена на изучение элементного состава листьев тополя как биогеохимического индикатора состояния окружающей среды городов с выраженной специализацией. Исследование проведено на примере города Тюмень.The work is directed at studying the elemental composition of poplar leaves as a biogeochemical indicator of the state of the environment of cities with a pronounced specialization. The study was conducted on the example of the city of Tyumen

Clinical relevance of molecular characteristics in Burkitt lymphoma differs according to age

While survival has improved for Burkitt lymphoma patients, potential differences in outcome between pediatric and adult patients remain unclear. In both age groups, survival remains poor at relapse. Therefore, we conducted a comparative study in a large pediatric cohort, including 191 cases and 97 samples from adults. While TP53 and CCND3 mutation frequencies are not age related, samples from pediatric patients showed a higher frequency of mutations in ID3, DDX3X, ARID1A and SMARCA4, while several genes such as BCL2 and YY1AP1 are almost exclusively mutated in adult patients. An unbiased analysis reveals a transition of the mutational profile between 25 and 40 years of age. Survival analysis in the pediatric cohort confirms that TP53 mutations are significantly associated with higher incidence of relapse (25 ± 4% versus 6 ± 2%, p-value 0.0002). This identifies a promising molecular marker for relapse incidence in pediatric BL which will be used in future clinical trials

Gallic and protocatechuic acid content during the development of Phycomyces bla­kesleeanus Bgff.

A quantitative determination method of gallic and protocatechuic acid in cultures and liquid nutrient of Phycomyces blakesleeanus was described. Both phenolic acids were separated by TLC and the colour reaction with Folin reagent was used for a colorimetric test. This procedure was employed for investigating the formation of gallic and protocatechuic acid in cultures with optimal (10-4 m) and reduced (1.3 × 10-6 ᴍ) zinc supply showing that their production is stimulated by zinc ions. In addition, the inhibiting effect of light on the accumulation of gallic acid was manifested, however, its excretion into the medium was uneffected by light and protocatechuic acid was not excreted at all. During the development of Phycomyces gallic and protocatechuic acid could be detected in two days old mycelium . With the sporangiophore production both acids are accumulated more rapidly in the sporangiophores. After the end of sporangiophore formation the gallic acid content increases only slightly. In contrast the total content of protocatechuic acid decreases sharply. As no excretion occurs a degradation of at least protocatechuic acid must be taken into consideration

Phosphoenolpyruvate carboxykinase in Phycomyces blakesleeanus Bgff.

Phosphoenolpyruvate carboxykinase (PEPCK) from Phycomyces blakesleeanus was partially purified by protamine sulfate precipitation, ammoniumsulfate precipitation, and diethylamino ethyl cellulose (DEAE) treatment. This preparation was employed for the characterization of the enzyme. The Km values for phosphoenolpyruvate (PEP) and ADP were determined as 1.6 and 0.42 mᴍ. The nucleotid specifity was demonstrated for ADP exclusively. The use of sulfuryl reagents showed the presence of thiol groups sensitive against p-hydroxymercuribenzoate but not effected by N-ethylmaleimide

Enzymatic preparation of 14C-labeled phytoene, squalene, and geranylgeranyl pyrophosphate from [2-14C]mevalonic ccid

Methods are described for an enzymatic preparation of 14C-labeled terpenoids. With a cell-free system of a white mutant of Phycomyces blakesleeanus (Mucoraceae) [14C]squalene and [14C- cis]phytoene can be synthesized from [2-14C]mevalonate. The application of norflurazon, a phenyl- pyridazinone herbicide, helps to increase the yield of squalene. Furthermore, the liquid endosperm of Echinocystis lobata (Cucurbitaceae) was used for the formation of either [14C(-)]kaurene from [14C]mevalonic acid or [14C-/ra/w]geranylgeranyl pyrophosphate in the presence of Amo 1618. The hydrocarbons formed were purified by alumina-column chromatography and preparative thin-layer chromatography (TLC). Geranylgeranyl pyrophosphate was separated by DE-column chromatography followed by TLC

Infrarenal transposition of the superior mesenteric artery: A new approach in the surgical therapy for Wilkie syndrome

The superior mesenteric artery syndrome, also known as Wilkie syndrome or as arteriomesenteric obstruction of the duodenum, is a rare condition of upper intestinal obstruction in which the third part of the duodenum is compressed by the overlying, narrow-angled superior mesenteric artery against the posterior structures. It is characterized by early satiety, recurrent vomiting, abdominal distention, weight loss, and postprandial distress. When nonsurgical management is not possible or the problem is refractory, surgical intervention is necessary. Usually a laterolateral duodenojejunostomy or Roux-en-Y reconstruction for reconstruction of the intestinal passage is performed. We report the first successful transposition, to our knowledge, of the superior mesenteric artery into the infrarenal aorta in the therapy of Wilkie syndrome