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91.
DP McHale S Mitchell S Bundey L Moynihan DA Campbell CG Woods NJ Lench RF Mueller AF Markham 《Canadian Metallurgical Quarterly》1999,64(2):526-532
Cerebral palsy has an incidence of approximately 1/500 births, although this varies between different ethnic groups. Genetic forms of the disease account for approximately 1%-2% of cases in most countries but contribute a larger proportion in populations with extensive inbreeding. We have clinically characterized consanguineous families with multiple children affected by symmetrical spastic cerebral palsy, to locate recessive genes responsible for this condition. The eight families studied were identified from databases of patients in different regions of the United Kingdom. After ascertainment and clinical assessment, we performed a genomewide search for linkage, using 290 polymorphic DNA markers. In three families, a region of homozygosity at chromosome 2q24-q25 was identified between the markers D2S124 and D2S148. The largest family gave a maximum LOD score of 3.0, by multipoint analysis (HOMOZ). The maximum combined multipoint LOD score for the three families was 5.75. The minimum region of homozygosity is approximately 5 cM between the markers D2S124 and D2S2284. We have shown that a proportion of autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25. The identification of genes involved in the etiology of cerebral palsy may lead to improved management of this clinically intractable condition. 相似文献
92.
Spectrin of the erythrocyte membrane skeleton is composed of alpha- and beta-spectrin, which associate to form heterodimers and tetramers. It has been suggested that a fractional domain (helix C) in the amino-terminal region of alpha-spectrin (Nalpha region) bundles with another fractional domain in the carboxyl-terminal region of beta-spectrin (Cbeta region) to yield a triple alpha-helical bundle and that this helical bundling is largely responsible for tetramer formation. However, there are certain objections to assigning a preeminent role to this helical bundling in the tetramerization reactions. We prepared several recombinant peptides of alpha-spectrin fragments spanning only the Nalpha region (lacking the dimer nucleation site) and quantitatively studied their interaction with beta-spectrin. We found that a majority of the interactions were localized, as expected, in the Nalpha-helix C region but that there was also some contribution from the nonhomologous region. More importantly, the temperature and ionic strength dependence of this interaction in our model peptides was different from that in intact spectrin. We suggest that, although the regions involving the putative helical bundling in alpha- and beta-spectrin undoubtedly play a significant role in tetramerization, regions distal to the Nalpha-helix C region in spectrin are also involved in tetramer formation. Structural flexibility and lateral interactions may play a role in spectrin tetramerization. 相似文献
93.
94.
CD Day NJ Smilinich GV Fitzpatrick PJ deJong TB Shows MJ Higgins 《Canadian Metallurgical Quarterly》1999,10(2):182-185
BACKGROUND: Right lower quadrant abdominal pain may pose a diagnostic problem in patients with cystic fibrosis. Abdominal ultrasound examination, used commonly in the diagnostic work-up, may reveal abnormalities of the appendix. However, interpretation of such findings is problematic, because the appearance of the gastrointestinal system during routine examination has not been documented in patients with cystic fibrosis. The purpose of this study was to investigate the findings during routine abdominal ultrasound scans in our cohort of patients with cystic fibrosis and in control subjects. METHODS: Abdominal ultrasound scans were performed prospectively during routine clinic visits in a cohort of patients with cystic fibrosis. RESULTS: Fifty patients aged 10+/-6 years, (range, 0.5-28 years) were examined; 45 had pancreatic insufficiency. Four patients (3 with pancreatic insufficiency) reported right lower quadrant pain at the time of the scan. According to standard ultrasound criteria, the appearance of the appendix was abnormal in 8 patients (16%), 6 had a mucoid appendix, and 2 had a pathologically thickened appendiceal wall. Only 1 of these 8 patients mentioned abdominal pain at the time of the study. Other incidental findings included gallstones (3 patients), intussusception (2 patients), and pancreatic cyst (1 patient). CONCLUSIONS: Abnormalities can be observed during routine abdominal ultrasonographic studies in cystic fibrosis. These findings may not be associated with abdominal pain; their clinical relevance needs further investigation. 相似文献
95.
96.
L Gao L Liu D van Meyel G Cairncross P Forsyth D Kimmel RB Jenkins NJ Lassam D Hogg 《Canadian Metallurgical Quarterly》1997,3(6):977-981
Gliomas are tumors of the central nervous system that may be inherited in some patients. The gene(s) responsible for the clustering of gliomas in families have not yet been identified. Molecular studies of sporadic high-grade gliomas have revealed mutations or deletions of the genes encoding the protein kinase inhibitors p16(INK4A) and p15(INK4B) in a large proportion of tumors. Moreover, those tumors without deletions frequently display gene amplification and/or over-expression of mRNA encoding the protein kinase cdk4. We hypothesized that germ-line mutations in the p16(INK4A), p15(INK4B), or CDK4 genes might contribute to some cases of familial gliomas. To address this issue, we analyzed 36 kindreds with a predisposition to glial tumors. Genomic DNA from index members of these families was screened by PCR-single-strand conformational polymorphism analysis. We did not detect any functional mutations in the p16(INK4A), p15(INK4B), or CDK4 genes, although two individuals did have a previously described A140T polymorphism in p16(INK4A). Thus, despite the association between the sporadic forms of high-grade glioma and abnormalities of p16(INK4A), p15(INK4B), or CDK4, we found no evidence that germ-line mutations in the coding region of these three genes predispose to inherited glial tumors. 相似文献
97.
98.
L Lyras NJ Cairns A Jenner P Jenner B Halliwell 《Canadian Metallurgical Quarterly》1997,68(5):2061-2069
Oxidative stress may contribute to neuronal loss in Alzheimer's disease (AD). The present study compares the levels of oxidative damage to proteins, lipids, and DNA bases from seven different brain areas of AD and matched control tissues by using a range of techniques. No differences in levels of lipid peroxidation were found in any of the brain regions by using two different assay systems. Overall, there was a trend for protein carbonyl levels to be increased in AD in frontal, occipital, parietal, and temporal lobe, middle temporal gyrus, and hippocampus, but a significant difference was found only in the parietal lobe. Gas chromatography-mass spectrometry was used to measure products of damage to all four DNA bases. Increased levels of some (8-hydroxyadenine, 8-hydroxyguanine, thymine glycol, Fapy-guanine, 5-hydroxyuracil, and Fapy-adenine), but not all, oxidized DNA bases were observed in parietal, temporal, occipital, and frontal lobe, superior temporal gyrus, and hippocampus. The baseline level of oxidative DNA damage in the temporal lobe was higher than in other brain regions in both control and AD brain. The finding of increased oxidative damage to protein and DNA strengthens the possibility that oxidative damage may play a role in the pathogenesis of AD in at least some key brain regions. 相似文献
99.
HS Matloub WW Dzwierzynski S Erickson JR Sanger NJ Yousif V Muoneke 《Canadian Metallurgical Quarterly》1996,21(3):451-455
This study was undertaken to determine the usefulness of magnetic resonance imaging (MRI) in the diagnosis of flexor tendon rupture in patients who had prior surgery. Magnetic resonance imaging scans were performed on 11 digits (16 tendons) with the clinical diagnosis of flexor tendon rupture. Clinical suspicion correlated with MRI and surgical findings. Clinical examination yielded a 60% accuracy in diagnosis. MRI differentiated rupture from adhesions with a 100% accuracy rate. The MRI scan is a valuable tool in diagnosing tendon ruptures and may help reduce the incidence of unnecessary tendon explorations. 相似文献
100.