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31.
Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency 总被引:1,自引:0,他引:1
Hong YS; Kerr DS; Craigen WJ; Tan J; Pan Y; Lusk M; Patel MS 《Human molecular genetics》1996,5(12):1925-1930
An infant girl with elevated blood lactate, pyruvate, and plasma
branched-chain amino acids was diagnosed with dihydrolipoamide
dehydrogenase (E3; dihydrolipoamide: NAD+ oxidoreductase, EC 1.8.1.4)
deficiency. Activities of the pyruvate dehydrogenase complex and E3 from
patient were 26 and 2% of controls in blood lymphocytes, and 11 and 14% in
cultured skin fibroblasts, respectively. Western blot analysis demonstrated
that the amount of E3 protein in fibroblasts from the patient and her
father was about half of controls, while Northern blot analysis showed
normal amounts of E3 RNA. DNA sequencing of cloned full-length E3 cDNAs
from the patient revealed two mutations in separate alleles. One is a
single base insertion of an extra adenine in the last codon of the leader
peptide sequence (TAC-->TAAC) leading to a nonsense mutation which
results in the premature termination of the precursor E3 polypeptide
(Y35X). The other is a missense mutation due to substitution of guanine for
adenine, causing an Arg-->Gly substitution at amino acid 460 of the
mature protein (R460G) which triggers the loss of E3 activity probably by
structural change in the E3 dimer. DNA sequencing of E3 cDNAs from the
parents demonstrated that the nonsense mutation was inherited from the
father and the missense mutation was inherited from the mother.
相似文献
32.
Lesions of the articular surfaces of the knee have been managed by various techniques over the last 50 years. Surgical management has involved: excising the damaged area, refashioning the underlying bone to produce a fibrous response, and introducing allograft, autograft and synthetic materials to encourage a repair matrix. The techniques and their pitfalls are reviewed and discussed, and suggestions made as to the direction of future studies for the repair of osteochondral lesions in the painful knee. 相似文献
33.
Peanut lectin (PNA) binds to D Gal B (1-3) D Gal NAc which is the purported antigenic determinant of the so-called T blood group antigen (TAg). We used PNA in an indirect immunofluorescent technique to study TAg in transitional cell carcinomas of the bladder (TCC). All 14 control tissues failed to express TAg, whereas all controls (100%) expressed TAg on the cell membrane after prior treatment with neuraminidase. Sixty-nine percent of Stage O TCC expressed TAg, whereas 100% of cases expressed TAg after treatment with neuraminidase. Staining patterns noted were: granular intracytoplasmic, intracytoplasmic globular, and membrane. There was no correlation between TAg positivity or negativity and subsequent muscle wall invasion in the Stage O TCC group. Fifty percent of Stage B or greater TCC expressed TAg, whereas 27 of 30 (90%) cases expressed TAg after neuraminidase treatment. TAg-staining patterns noted in Stage B tumors were: membrane, granular intracytoplasmic, intracytoplasmic globular, and glycocalyx. Only 47% of Grade III TCC expressed TAg compared with 72% of low-grade TCC. The authors conclude that the expression of TAg reflects the neoplastic transformation of bladder epithelium. The data also suggest that in TCC, TAg positivity is most likely due to incomplete synthesis of MN blood group glycoprotein, as evidenced by loss of a terminal sialic acid, and that there is also evidence of cytostructural "relocalization" of TAg. 相似文献
34.
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36.
Effect of age and breast density on screening mammograms with false-positive findings 总被引:4,自引:0,他引:4
Lehman CD White E Peacock S Drucker MJ Urban N 《AJR. American journal of roentgenology》1999,173(6):1651-1655
OBJECTIVE: The objective of this study was to examine the effect of breast density and age on screening mammograms with false-positive findings. MATERIALS AND METHODS: The study sample was taken from the Washington State Mammography Tumor Registry, which links data from participating radiologists with the Puget Sound Cancer Surveillance System and the Washington State Cancer Registry. Participants (n = 73,247) were women 35 years old and older who underwent screening mammography for which an assessment and a four-category density rating were coded. A total of 46,340 mammograms were sampled to avoid interpreter bias. In this study of false-positive mammograms, only women with no diagnosis of breast cancer within 12 months of the index mammogram were included. Logistic regression was used to estimate the odds ratios of a false-positive mammogram being associated with each category of breast density or age, adjusting for the other factor as a covariate. RESULTS: After controlling for breast density, we found that the risk of a false-positive mammogram was not affected by age (p = 27). However, the trend of increasing risk of a false-positive mammogram with increasing breast density was highly significant (p < .001). Women with extremely dense breast tissue were almost two times more likely to have a false-positive mammogram than were women with fatty breast tissue. This effect persisted after controlling for age. CONCLUSION: Breast density, not age, is an important factor when predicting risk of a false-positive mammogram. Breast density should be considered when educating individual women on the risks and benefits of screening mammography. 相似文献
37.
It is well established that the mammalian circadian system consists of pacemaker cells in the suprachiasmatic nuclei (SCN). The mouse has become increasingly important in understanding the circadian timing system, due to the availability of mutant animals with abnormal circadian rhythms. In the present paper, we describe the organization of the mouse SCN, comparing the wild type and Clock mutant animal, with a special focus on those peptides bearing an upstream E-box element (vasopressin, vasoactive intestinal peptide, cholecystokinin and substance P). To this end, we describe the distribution of the foregoing SCN peptidergic cell types as well as gastrin-related peptide, calretinin, calbindin, somatostatin, neurotensin and retinal input to the SCN (determined by both tract tracing and fos-immunoreactivity in response to a light pulse). The Clock mutant mouse has decreased expression of vasopressin mRNA and protein in the SCN, with normal patterns of expression elsewhere in the brain. No other differences were detected between the Clock mutant and the wild type mouse. The results are consistent with the hypothesis that there are multiple regulatory elements of clock-controlled genes in the SCN. 相似文献
38.
The well-being of chronic mental patients 总被引:17,自引:0,他引:17
A F Lehman 《Archives of general psychiatry》1983,40(4):369-373
The concept, "quality of life" (QOL), offers a broad perspective for assessing the needs and outcomes of chronic mental patients. In this survey of Los Angeles board-and-care homes, 278 randomly selected, mentally disabled residents evaluated their QOL in structured interviews based on a general QOL model. Life areas studied included living situation, family, social relations, leisure, work, safety, finances, and health. The model performed as well among these residents as among the general population, explaining 48% to 58% of the variance in global well-being. Adding patients' subjective QOL evaluations doubled the explanatory power of a model based only on personal characteristics and objective life conditions. Global well-being was most consistently associated with personal safety, social relations, finances, leisure, and health care variables. The study identifies methodological and service issues in need of further examination. 相似文献
39.
Mortality rates were examined among 3,324 Black and White daily opioid drug users for a four-year period following treatment in community-based agencies located across the United States. A total of 179 of these addicts died during this follow-up period, yielding a death rate of 15.2 per 1,000 person-years at risk. When adjusted for age, addict death rates were found to be three to 14 times higher than those in the general US population. Life table analysis was also used to examine these rates in relation to client demographic, background, and treatment variables obtained prospectively, both prior to and during treatment. Age, alcohol use, and criminal history were positively associated with higher death rates. With regard to causes of death, age proved to be the only significant predictor; older addicts (over 30) had the highest percentages of deaths due to "natural" causes, while over three-fourths of the deaths among younger addicts were drug related or involved violence. 相似文献
40.