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11.
For complex genetic diseases involving incomplete penetrance, genetic heterogeneity, and multiple disease genes, it is often difficult to determine the molecular variant(s) responsible for the disease pathogenesis. Linkage and association studies may help identify genetic regions and molecular variants suspected of being directly responsible for disease predisposition or protection, but, especially for complex diseases, they are less useful for determining when a predisposing molecular variant has been identified. In this paper, we expand upon the simple concept that if a genetic factor predisposing to disease has been fully identified, then a parent homozygous for this factor should transmit either of his/her copies at random to any affected children. Closely linked markers are used to determine identity by descent values in affected sib pairs from a parent homozygous for a putative disease predisposing factor. The expected deviation of haplotype sharing from 50%, when not all haplotypes carrying this factor are in fact equally predisposing, has been algebraically determined for a single locus general disease model. Equations to determine expected sharing for multiple disease alleles or multiple disease locus models have been formulated. The recessive case is in practice limiting and therefore can be used to estimate the maximum proportion of putative susceptibility haplotypes which are in fact predisposing to disease when the mode of inheritance of a disease is unknown. This method has been applied to 27 DR3/DR3 parents and 50 DR4/DR4 parents who have at least 2 children affected with insulin dependent diabetes mellitus (IDDM). The transmission of both DR3 and DR4 haplotypes is statistically different from 50% (P < 0.05 and P < 0.001, respectively). An upper estimate for the proportion of DR3 haplotypes associated with a high IDDM susceptibility is 49%, and for DR4 haplotypes 38%. Our results show that the joint presence of non-Asp at DQ beta position 57 and Arg at DQ alpha position 52, which has been proposed as a strong IDDM predisposing factor, is insufficient to explain the HLA component of IDDM predisposition. 相似文献
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Communication between patients with breast cancer and health care providers. Determinants and implications 总被引:1,自引:0,他引:1
C Lerman M Daly WP Walsh N Resch J Seay A Barsevick L Birenbaum T Heggan G Martin 《Canadian Metallurgical Quarterly》1993,72(9):2612-2620
BACKGROUND: This study evaluated the perceptions of patients with breast cancer of their medical interactions with providers. The determinants and psychological consequences of communication problems also were examined. METHODS: Ninety-seven patients with Stage I or II breast cancer completed a set of validated questionnaires before initiating postoperative therapy. Data on psychological distress were collected at baseline and 3-month follow-up, and multivariate models were fit to explain the relationship between pretreatment communication problems and subsequent psychological distress. Data on clinical variables were abstracted from medical records. RESULTS: A substantial proportion of patients (84%) reported difficulties communicating with the medical team. Communication problems were more common among patients who were less optimistic about their disease and had less assertive coping styles. Patient-reported communication problems were associated with increased anxiety, depression anger, and confusion at the 3-month follow-up. The association between communication problems and mood disturbance remained significant, although small, after adjusting for baseline mood disturbance, demographic, clinical, and coping style variables. CONCLUSION: Interventions that enhance communication between patients with breast cancer and their providers may improve patients' psychological adjustment to treatment. Conversely, interventions that lower distress and modify coping style may enhance communication. 相似文献
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1. The classical ATP sensitive K+ (K(ATP)) channels are composed of a sulphonylurea receptor (SUR) and an inward rectifying K+ channel subunit (BIR/Kir6.2). They are the targets of vasorelaxant agents called K+ channel openers, such as pinacidil and nicorandil. 2. In order to examine the tissue selectivity of pinacidil and nicorandil, in vitro, we compared the effects of these agents on cardiac type (SUR2A/Kir6.2) and vascular smooth muscle type (SUR2B/Kir6.2) of the K(ATP) channels heterologously expressed in HEK293T cells, a human embryonic kidney cell line, by using the patch-clamp method. 3. In the cell-attached recordings (145 mM K+ in the pipette), pinacidil and nicorandil activated a weakly inwardly-rectifying, glibenclamide-sensitive 80 pS K+ channel in both the transfected cells. 4. In the whole-cell configuration, pinacidil showed a similar potency in activating the SUR2B/Kir6.2 and SUR2A/Kir6.2 channels (EC50 of approximately 2 and approximately 10 microM, respectively). On the other hand, nicorandil activated the SUR2B/Kir6.2 channel > 100 times more potently than the SUR2A/Kir6.2 (EC50 of approximately 10 microM and > 500 microM, respectively). 5. Thus, nicorandil, but not pinacidil, preferentially activates the K(ATP) channels containing SUR2B. Because SUR2A and SUR2B are diverse only in 42 amino acids at their C-terminal ends, it is strongly suggested that this short part of SUR2B may play a critical role in the action of nicorandil on the vascular type classical K(ATP) channel. 相似文献
18.
R. A. Farrar Z. Zhang S. R. Bannister G. S. Barritte 《Journal of Materials Science》1993,28(5):1385-1390
The influence of prior austenite grain size on the transformation behaviour and microstructural development of C-Mn-Ni weld metals was investigated. It was found that increasing the grain size depressed the start temperature of grain-boundary ferrite and slightly increased the acicular ferrite start temperature. The microstructural products also changed from a boundary-dominated effect in the small grain sizes, to an intragranular-dominated effect in the large grain sizes, and at the same time, the morphology of the acicular ferrite was seen to change to a larger aspect ratio. 相似文献
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AM Moody WP Mayles JM Bliss RP A'Hern JR Owen J Regan B Broad JR Yarnold 《Canadian Metallurgical Quarterly》1994,33(2):106-112
A prospective assessment of late changes in breast appearance in 559 patients after tumour excision and radiotherapy for early breast cancer noted a strong association with breast size. Only 3/48 (6%) patients with small breasts developed moderate or severe late changes compared with 94/423 (22%) with medium sized breasts and 34/88 (39%) patients with large breasts (p < 0.001). One possibility is that greater radiation changes are related to greater dose inhomogeneity in women with large breasts. To explore this hypothesis, radiation dose distributions were assessed in a separate group of 37 women in whom three-level transverse computer tomographic images of the breast in the treatment position were available. A significant correlation was found between breast size and dose inhomogeneity which may account for the marked changes in breast appearance reported in women with large breasts. 相似文献
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BACKGROUND AND PURPOSE: The purpose of this study was to examine the effect of isometric training of the quadriceps femoris muscles, at different joint angles, on torque production and electromyographic (EMG) activity. SUBJECTS: One hundred seven women were randomly assigned to one of four groups. Three groups trained with isometric contractions three times per week at a knee flexion angle of 30, 60, or 90 degrees. The fourth group, which served as a control, did not exercise. METHODS: Isometric torque was measured using a dynamometer, and EMG activity was measured using a multichannel EMG system. Measurements were obtained during maximal isometric contraction of the quadriceps femoris muscles at 15-degree increments from 15 to 105 degrees of knee flexion. Measurements were taken before and after 8 weeks of training. RESULTS: Following isometric exercise, increased torque and EMG activity occurred not only at the angle at which subjects exercised, but also at angles in the range of motion at which exercise did occur. Further analyses indicated that exercising in the lengthened position for the quadriceps femoris muscles (90 degrees of knee flexion) produced increased torque across all angles measured and appeared to be the more effective position for transferring strength and EMG activity to adjacent angles following isometric training as compared with the shorter positions of the muscle (30 degrees and 60 degrees of knee flexion). CONCLUSION AND DISCUSSION: These findings suggest that an efficient method for increasing isometric knee extension torque and EMG activity throughout the entire range of motion is to exercise with the quadriceps femoris muscles in the lengthened position. 相似文献