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991.
Olsen RK Andresen BS Christensen E Mandel H Skovby F Nielsen JP Knudsen I Vianey-Saban C Simonsen H Gregersen N 《Prenatal diagnosis》2005,25(1):60-64
OBJECTIVES: Multiple acyl-CoA dehydrogenation deficiency (MADD) is a clinically heterogeneous disorder of mitochondrial fatty acid, amino acid, and choline oxidation due to mutations in the genes encoding electron transfer flavoprotein (ETF) or ETF ubiquinone oxidoreductase (ETFQO). So far, prenatal diagnosis of MADD has relied mostly on second-trimester biochemical analyses of amniotic fluid or cultured amniocytes. We report here on an alternative DNA-based approach for prenatal diagnosis in pregnancies at risk of MADD. METHODS: We used our knowledge of the mutational status in three unrelated families with a history of MADD to perform direct sequencing for the familial mutations using genomic DNA isolated from chorionic villus samples (CVS) at gestational week 10 to 11. RESULTS: Within two days, we were able to carry out accurate DNA-based prenatal testing in one pregnancy at risk of severe MADD, and in two pregnancies at risk of variant forms of MADD. CONCLUSION: This is the first report of DNA-based prenatal diagnosis of MADD. Our molecular approach is suitable for fast and reliable first-trimester prenatal diagnosis in pregnancies at risk of severe and variant forms of MADD. 相似文献
992.
Fenger MM Gade A Adams KH Hansen ES Bolwig TG Knudsen GM 《Nordic journal of psychiatry》2005,59(1):39-44
Individuals with obsessive-compulsive disorder (OCD) display frontal lobe deficits, but there are inconsistencies between various tests of frontal lobe functions and between the results from different studies. The objective of this work was to characterize frontal lobe dysfunctions in OCD patients. Fifteen patients and 17 control subjects matched for age, sex and intelligence were tested on classic tests of frontal lobe functions [Wisconsin Card Sorting Test (WCST) and tests of fluency], a smell identification test and one computerized test: the Intra/Extra Dimension test. The Intra/Extra Dimension test showed a significant difference between the two groups in reversal of response. The test of Figural fluency showed a significant difference between the two groups in numbers of produced figures. There were no differences on the WCST, verbal fluency and the smell identification test. 相似文献
993.
Gene expression arrays reveal the potential linkage of altered gene expression with specific adverse effects leading to disease phenotypes. But how closely do microarray data reflect early physiological or pharmacological measures that predict toxic event(s)? To explore this issue, we have undertaken experiments in early mouse embryos exposed to various teratogens during neurulation stages with the aim of correlating large-scale changes in gene expression across the critical period during exposure. This study reports some of the large-scale changes in gene expression that can be detected in the optic rudiment of the developing mouse and rat embryo across the window of development during which the eye is exceedingly sensitive to teratogen-induced micro-/anophthalmia. Microarray analysis was performed on RNA from the headfold or ocular region at the optic vesicle and optic cup stages when the ocular primordium is enriched for Pax-6, a master control gene for eye morphogenesis. Statistical selection of differentially regulated genes and various clustering techniques identified groups of genes in upward or downward trajectories in the normal optic primordium during early eye development in mouse and rat species. We identified 165 genes with significant differential expression during eye development, and a smaller subset of 58 genes that showed a tight correlation between mouse-rat development. Significantly over-represented functional categories included fatty acid metabolism (up-regulated) and glycolysis (down-regulated). From studies such as these that benchmark large-scale gene expression during normal embryonic development, we may be able to identify the panel of biomarkers that best correlate with species differences and the risks for developmental toxicity. 相似文献
994.
The influence of high doses of 2 chelating agents, D-penicillamine and iodochlorohydroxyquin, on the metabolism of orally ingested 65 Zn was studied on rats by means of whole body counting assay technique. Both drugs were found to increase zinc absorption in a dose-dependent way to values significantly above those of the untreated control group. At identical doses D-penicillamine had a significantly stronger enhancing effect than the 8-hydroxyquinoline derivate, except for the highest dosage which was 100 mg daily. The turnover of the absorbed 65Zn fraction was followed during the time of observation which was 11 days. The elimination rate was practically identical in all experimental groups, except for the 100 mg D-penicillamine group in which the biological half-life of 65Zn was significantly decreased as compared to the control group. 相似文献
995.
Protein C activity in renal disease 总被引:1,自引:0,他引:1
Protein C activity was determined in 19 healthy controls and in 52 patients with renal diseases, clinically divided into three groups I) Nephrotic syndrome, II) Renal insufficiency, III) Terminal uremia, requiring maintenance dialysis. In the nephrotic syndrome protein C levels were found to be normal, but in renal insufficiency and terminal uremia the protein C activity was significantly decreased. A correlation between decreasing protein C and progressive renal failure is suggested. The reduced protein C activity may play an important role in the thrombotic tendency seen in renal diseases and uremia. 相似文献
996.
997.
Szabo G Hoek JB Darley-Usmar V Hajnoczky G Knudsen T Mochly-Rosen D Zakhari S 《Alcoholism, clinical and experimental research》2005,29(9):1749-1752
This article summarizes the proceedings of the RSA 2004 Combined Basic Research Satellite Meeting convened at the Westin Bayshore Resort and Marina, Vancouver, CA. One of the sessions "Alcohol and mitochondrial metabolism: At the crossroads of life and death" featured five speakers and was chaired by Drs. Jan Hoek and Sam Zakhari. The presentations were 1) Introduction: Alcohol and cellular energy metabolism by Jan Hoek, 2) Ethanol-dependent dysfunction of mitochondrial energy metabolism: the role of NO by Victor Darley-Usmar, 3) Ethanol and apoptosis in the heart by Gyorgy Hajnoczky, 4) Alcohol and mitochondrial biogenesis in development by Thomas Knudsen, and 5) Alcohol, mitochondrial function and cardiac preconditioning by Daria Mochly-Rosen. 相似文献
998.
Performance and safety of holmium: YAG laser optical fibers 总被引:2,自引:0,他引:2
Knudsen BE Glickman RD Stallman KJ Maswadi S Chew BH Beiko DT Denstedt JD Teichman JM 《Journal of endourology / Endourological Society》2005,19(9):1092-1097
BACKGROUND AND PURPOSE: Lower-pole ureteronephroscopy requires transmission of holmium:YAG energy along a deflected fiber. Current ureteroscopes are capable of high degrees of deflection, which may stress laser fibers beyond safe limits during lower-pole use. We hypothesized that optical fiber and safety measures differ among manufacturers. MATERIALS AND METHODS: Small (200-273-microm) and medium-diameter (300-400-microm) Ho:YAG fibers were tested in a straight and 180 degrees bent configuration. Energy transmission was measured by an energy detector. Fiber durability was assessed by firing the laser in sequentially tighter bending diameters. The fibers were bent to 180 degrees with a diameter of 6 cm and run at 200- to 4000-mJ pulse energy to determine the minimum energy required to fracture the fiber. The bending diameter was decreased by 1-cm increments and testing repeated until a bending diameter of 1 cm was reached. The maximum deflection of the ACMI DUR-8E ureteroscope with each fiber in the working channel was recorded. The flow rate through the working channel of the DUR-8E was measured for each fiber. RESULTS: The mean energy transmission differed among fibers (P < 0.001). The Lumenis SL 200 and the InnovaQuartz 400 were the best small and medium-diameter fibers, respectively, in resisting thermal breakdown (P < 0.01). The Dornier Lightguide Super 200 fractured repeatedly at a bend diameter of 2 cm and with the lowest energy (200 mJ). The other small fibers fractured only at a bend diameter of 1 cm. The Sharplan 200 and InnovaQuartz Sureflex 273T were the most flexible fibers, the Lumenis SL 365 the least. The flow rate was inversely proportional to four times the power of the diameter of the fiber. CONCLUSIONS: Optical performance and safety differ among fibers. Fibers transmit various amounts of energy to their cladding when bent. During lower-pole nephroscopy with the fiber deflected, there is a risk of fiber fracture from thermal breakdown and laser-energy transmission to the endoscope. Some available laser fibers carry a risk of ureteroscope damage. 相似文献
999.
Papadopoulos V Baraldi M Guilarte TR Knudsen TB Lacapère JJ Lindemann P Norenberg MD Nutt D Weizman A Zhang MR Gavish M 《Trends in pharmacological sciences》2006,27(8):402-409
The peripheral-type benzodiazepine receptor or recognition site (PBR) is a widely distributed transmembrane protein that is located mainly in the outer mitochondrial membrane. The PBR binds to high-affinity drug ligands and cholesterol. Many functions are associated directly or indirectly with the PBR, including the regulation of cholesterol transport and the synthesis of steroid hormones, porphyrin transport and heme synthesis, apoptosis, cell proliferation, anion transport, regulation of mitochondrial functions and immunomodulation. Based on these functions, there are many potential clinical applications of PBR modulation, such as in oncologic, endocrine, neuropsychiatric and neurodegenerative diseases. Although "PBR" is a widely used and accepted name in the scientific community, recent data regarding the structure and molecular function of this protein increasingly support renaming it to represent more accurately its subcellular role (or roles) and putative tissue-specific function (or functions). Translocator protein (18kDa) is proposed as a new name, regardless of the subcellular localization of the protein. 相似文献
1000.
The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms 总被引:8,自引:0,他引:8
The greatest risk factor for developing carcinoma of the prostate is advanced age. Potential molecular and physiologic contributors to the frequency of cancer occurrence in older individuals include the accumulation of somatic mutations through defects in genome maintenance, epigenetic gene silencing, oxidative stress, loss of immune surveillance, telomere dysfunction, chronic inflammation, and alterations in tissue microenvironment. In this context, the process of prostate carcinogenesis can be influenced through interactions between intrinsic cellular alterations and the extrinsic microenvironment and macroenvironment, both of which change substantially as a consequence of aging. In this study, we sought to characterize the molecular alterations that occur during the process of prostate fibroblast senescence to identify factors in the aged tissue microenvironment capable of promoting the proliferation and potentially the neoplastic progression of prostate epithelium. We evaluated three mechanisms leading to cell senescence: oxidative stress, DNA damage, and replicative exhaustion. We identified a consistent program of gene expression that includes a subset of paracrine factors capable of influencing adjacent prostate epithelial growth. Both direct coculture and conditioned medium from senescent prostate fibroblasts stimulated epithelial cell proliferation, 3-fold and 2-fold, respectively. The paracrine-acting proteins fibroblast growth factor 7, hepatocyte growth factor, and amphiregulin (AREG) were elevated in the extracellular environment of senescent prostate fibroblasts. Exogenous AREG alone stimulated prostate epithelial cell growth, and neutralizing antibodies and small interfering RNA targeting AREG attenuated, but did not completely abrogate the growth-promoting effects of senescent fibroblast conditioned medium. These results support the concept that aging-related changes in the prostate microenvironment may contribute to the progression of prostate neoplasia. 相似文献