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101.
Bastian W 《Journal of pediatric endocrinology & metabolism : JPEM》2002,15(Z1):471-484
Complex diseases, such as type 2 diabetes mellitus (T2DM), arise from metabolic disruptions with genetic and environmental components. Multiple genes are responsible for the genetic susceptibility to T2DM. The contribution of these genes to the diabetic phenotype may be modest, variable among different populations, and dependent on interactions with other genes and the environment. The methods of genetic dissection based on linkage, allele sharing, and linkage disequilibrium may lack the statistical power to detect weak associations in heterogeneous populations. Nevertheless, genes involved in insulin signaling, insulin secretion, insulin resistance, glucose metabolism, obesity, diabetes comorbidity and the hormone processing protease genes have been associated with T2DM. New research strategies are improving the methods of genetic dissection and include genomic sequence information to characterize profiles of sequence variants that predispose to T2DM. 相似文献
102.
Voluntary action is goal-directed and therefore depends on the ability to learn associations between movements and their perceivable consequences. The neural substrate of this ability was investigated with H2(15O) positron emission tomography (PET). Healthy adults first learned that self-initiated keypresses were consistently followed by certain tones (i.e., action effects). During PET imaging, participants listened to varied ratios of action-effect tones and neutral tones without performing any movement. The caudal supplementary motor area and the right hippocampus increased their activity with the frequency of action-effect tones, suggesting that both cortical areas play a role in linking the consequences of an action and the action itself. This integration process represents a highly flexible mechanism that helps to promote the learning, automatization, and control of voluntary 相似文献
103.
104.
Increased expression of RelA/nuclear factor-kappa B protein correlates with colorectal tumorigenesis 总被引:22,自引:0,他引:22
Yu HG Yu LL Yang Y Luo HS Yu JP Meier JJ Schrader H Bastian A Schmidt WE Schmitz F 《Oncology》2003,65(1):37-45
OBJECTIVE: To identify the role of RelA/nuclear factor-kappa B, an important inhibitor of apoptosis in colorectal tumorigenesis, we examined the expression of RelA in normal colorectal mucosa (n = 10), colorectal adenomas (n = 30) and colorectal adenocarcinomas (n = 30). Furthermore, the association of RelA expression with tumor cell apoptosis, proliferation, and expression of Bcl-2/Bcl-x(L )was also studied. METHODS: Paraffin sections were stained with monoclonal antibodies directed against RelA, Bcl-2, Bcl-x(L), and Ki-67 to assess protein expression patterns in normal, adenomatous and colon cancer tissue. Apoptotic cells were detected by terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling (TUNEL) using an in situ detection kit. RESULTS: The results of immunohistochemical staining revealed that expression of RelA, Bcl-2, Bcl-x(L), and Ki-67 labeling index (LI) significantly increased in the transition from adenoma with low dysplasia to adenocarcinoma. This transition was associated with a significant decrease in the apoptotic index (AI) and a significant increase in the Ki-67 LI. The expression of RelA correlated inversely with the AI and correlated positively with the expression of Bcl-2, Bcl-x(L), and Ki-67 LI in the transition from low-grade dysplasia to adenocarcinoma. CONCLUSION: Our results suggest that increased expression of RelA/nuclear factor-kappa B plays an important role in the transition from colorectal adenoma with low-grade dysplasia to adenocarcinoma in the pathogenesis of colon cancer in humans. 相似文献
105.
106.
While a goal-directed movement is prepared, motor cortical neurons selectively change their activity in relation to prior information about movement direction. Only little is known, however, about the neuronal representation of partial information about this parameter. We investigated this question by training monkeys in a multidirectional centre-out pointing task. A preparatory signal provided prior information about one, two or three possible adjacent targets, thus manipulating the level of certainty about movement direction. After a 1-s delay, the response signal specified one of the precued targets to indicate the actual movement to be performed. Based on the directional tuning curves of individual motor cortical neurons determined during the reaction time interval, we constructed distributions of the population activation (DPAs), which we were then able to estimate as well during the preparatory period. We found that these distributions were preshaped by prior information, with peaks of activation centred over the range of precued movement directions. These peaks sharpened as the response signal approached, and shifted to the specified movement direction subsequent to that signal. Wider ranges of precued movement directions were represented by broader DPAs. Trials in which monkeys produced short reaction times were characterized by narrower distributions than trials with long reaction times. Our study thus provides evidence for (i) a graded preshaping of the neuronal population representation of movement direction by partial information about this parameter, and (ii) the continuous evolution of the preshaped population representation during the preparatory period towards movement initiation. 相似文献
107.
Marker P Nielsen A Bastian HL 《The British journal of oral & maxillofacial surgery》2000,38(5):422-426
This study was designed to record the results of conservative treatment of condylar fractures and to find out if there were any variables that were predictive of complications. Data were analysed in our computer department. During the period 1984-1996, all patients who presented with a fracture of the mandibular condyle and who attended for control examination one year after treatment were recorded at the end of treatment and one year later. The ability to open the mouth, deviation and occlusion were recorded. After one year 45 of the 348 patients (13%) had minor physical complaints such as reduced ability to open the mouth, deviation, or dysfunction. Ten of them (3%) had pain in the joint or muscles or both. Eight patients (2%) had malocclusion, which in seven could be related to dislocation of the condylar head out of the fossa. Five of the eight patients had had bilateral fractures. We conclude that conservative treatment of condylar fractures is non-traumatic, safe, and reliable and in only a few cases may cause disturbances of function and malocclusion. The risk associated with the latter is greatest with bilateral fractures and dislocation of the condylar head from the fossa. 相似文献
108.
Mutations of the DPC4/Smad4 gene in neuroendocrine pancreatic tumors. 总被引:10,自引:0,他引:10
D Bartsch S A Hahn K D Danichevski A Ramaswamy D Bastian H Galehdari P Barth W Schmiegel B Simon M Rothmund 《Oncogene》1999,18(14):2367-2371
Tumors of the endocrine pancreas are extremely rare, and molecular mechanisms leading to their development are not well understood. A candidate tumor suppressor gene, DPC4, located at 18q21, has recently been shown to be inactivated in half of pancreatic adenocarcinoma xenografts. The close anatomical relationship of the exocrine and endocrine pancreas prompted us to determine the role of DPC4 in the tumorigenesis of 25 pancreatic islet cell tumors (11 insulinomas, nine non-functioning endocrine carcinomas, three gastrinomas, two vipomas). A mutation screening of the highly conserved COOH-terminal domain of DPC4 (exons 8-11) was performed by single-strand conformational variant (SSCP) analysis and a PCR-based deletion assay. Five of nine (55%) non-functioning endocrine pancreatic carcinomas revealed either point mutations, small intragenic deletions or homozygous deletion of DPC4 sequences compared to none of the insulinomas, gastrinomas or vipomas. These results suggest that DPC4 is an important target gene promoting tumorigenesis of non-functioning neuroendocrine pancreatic carcinomas. 相似文献
109.
Hydrostatic reduction of ileocolic intussusception: a second attempt in the operating room with general anesthesia 总被引:1,自引:0,他引:1
D L Collins L E Pinckney K E Miller J F Bastian D O Katzman T G Canty J Waldman 《The Journal of pediatrics》1989,115(2):204-207
Over a 3-year-period, standard treatment with hydrostatic pressure from a contrast enema failed to reduce ileocolic intussusception in 31 of 62 children. With the child anesthetized in the operating room, a second contrast enema was given before laparotomy. Of the 31 intussusceptions, 21 (68%) were reduced without complication, thereby avoiding the discomfort, longer hospitalization, complications, and expense of surgery. Nine of the remaining 10 intussusceptions were difficult to reduce manually during surgery or required resection. The overall nonoperative reduction rate for the 3-year period was 84%; for the last 2 years it was 90%. Success with the second enema may be related to the effects of general anesthesia. In addition, partial reduction with the first enema may improve blood flow from the intussusceptum so that it becomes smaller and easier to reduce with the second enema. Because it can easily be added to standard management protocols without increased risk, routine use of this second enema with anesthesia is recommended. 相似文献
110.
Photometric determination of phospholipase A 总被引:2,自引:0,他引:2
G E Hoffmann D Schmidt B Bastian W G Guder 《Zeitschrift für klinische Chemie und klinische Biochemie》1986,24(11):871-875
A photometric method for the determination of phospholipase A is described, in which fatty acids are liberated from phosphatidylcholine and measured by a discontinuous enzymatic test. Optimal test conditions were evaluated using purified phospholipase A from human and porcine pancreas. The enzyme activities measured in normal human sera are in the range of 0 to 10 U/l. Pathological values reach more than 100 U/l. There is no correlation with the activities of lipase or amylase in cases of acute pancreatitis. 相似文献