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991.
Richards AJ; Yates JR; Williams R; Payne SJ; Pope FM; Scott JD; Snead MP 《Human molecular genetics》1996,5(9):1339-1343
Stickler syndrome (hereditary arthro-ophthalmopathy) is the commonest
inherited cause of retinal detachment and one of the commonest autosomal
dominant connective tissue dysplasias. There is clinical and locus
heterogeneity with about two thirds of families linked to the gene encoding
type II procollagen (COL2A1). Families with Sticklers syndrome type 1 have
a characteristic congenital vitreous anomaly and are linked without
recombination to markers at the COL2A1 locus. In contrast families with the
type 2 variety have a different vitreo- retinal phenotype and are not
linked to the COL2A1 gene. Type XI collagen is a quantitatively minor
fibrillar collagen related to type V collagen and associated with the more
abundant type II collagen fibrils. A mutation in COL11A2, the gene for
alpha 2 (XI) procollagen, has recently been found in a family described as
having Stickler syndrome, although there was no ocular involvement. Here we
show for the first time that a family with the full Type 2 Stickler
syndrome including vitreous and retinal abnormalities is linked to the
COL11A1 gene and characterise the mutation as a Glycine to Valine
substitution at position 97 of the triple helical domain caused by a single
base G-- >T mutation. These results are the first to provide
confirmation that type XI collagen is an important structural component of
human vitreous. They also support previous work suggesting that mutations
in the genes encoding collagen XI can give rise to some manifestations of
Stickler syndrome, but of these, only mutations in COL11A1 will give the
full syndrome including the vitreo-retinal features.
相似文献
992.
Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function 总被引:10,自引:1,他引:9 下载免费PDF全文
Gilliland FD Berhane K McConnell R Gauderman WJ Vora H Rappaport EB Avol E Peters JM 《Thorax》2000,55(4):271-276
BACKGROUND: Exposure to environmental tobacco smoke (ETS) during childhood and in utero exposure to maternal smoking are associated with adverse effects on lung growth and development. METHODS: A study was undertaken of the associations between maternal smoking during pregnancy, exposure to ETS, and pulmonary function in 3357 school children residing in 12 Southern California communities. Current and past exposure to household ETS and exposure to maternal smoking in utero were assessed by a self-administered questionnaire completed by parents of 4th, 7th, and 10th grade students in 1993. Standard linear regression techniques were used to estimate the effects of in utero and ETS exposure on lung function, adjusting for age, sex, race, Hispanic ethnicity, height, weight, asthma, personal smoking, and selected household characteristics. RESULTS: In utero exposure to maternal smoking was associated with reduced peak expiratory flow rate (PEFR) (-3.0%, 95% CI -4.4 to -1.4), mean mid expiratory flow (MMEF) (-4.6%, 95% CI -7.0 to -2.3), and forced expiratory flow (FEF(75)) (-6.2%, 95% CI -9.1 to -3.1), but not forced expiratory volume in one second (FEV(1)). Adjusting for household ETS exposure did not substantially change these estimates. The reductions in flows associated with in utero exposure did not significantly vary with sex, race, grade, income, parental education, or personal smoking. Exposure to two or more current household smokers was associated with reduced MMEF (-4.1%, 95% CI -7.6 to -0. 4) and FEF(75) (-4.4%, 95% CI -9.0 to 0.4). Current or past maternal smoking was associated with reductions in PEFR and MMEF; however, after adjustment for in utero exposure, deficits in MMEF and FEF(75) associated with all measurements of ETS were substantially reduced and were not statistically significant. CONCLUSIONS: In utero exposure to maternal smoking is independently associated with decreased lung function in children of school age, especially for small airway flows. 相似文献
993.
994.
Leach FS Velasco A Hsieh JT Sagalowsky AI McConnell JD 《The Journal of urology》2000,164(5):1830-1833
PURPOSE: Mismatch repair genes are responsible for the coordinated correction of misincorporated nucleotides formed during DNA replication. Inactivating and inherited mutations in the prototypic mismatch repair gene hMSH2 have been described in a cancer predisposition syndrome known as hereditary nonpolyposis colon cancer. Patients with hereditary nonpolyposis colon cancer are at increased risk for colon cancer and extracolonic cancers such as upper tract transitional cell carcinoma but not prostate cancer. We investigated expression of hMSH2 in prostate cancer cell lines using genetic and molecular analysis. MATERIALS AND METHODS: We used the 3 well described prostate cancer cell lines, DU145, LNCaP and PC3. Western blot analysis with monoclonal antibody to hMSH2 was used to assess expression. Southern blot and polymerase chain reaction of genomic DNA were used to identify genetic alterations in the hMSH2 gene. Single cell cloning, dinucleotide repeats and BAT-26 were used to assess the cell lines for microsatellite instability. RESULTS: The prostate cancer cell line LNCaP did not express hMSH2 and was found to have a homozygous deletion of hMSH2 exons 9 to 16, resulting in truncation of the protein. While microsatellite analysis did not reveal alterations at the BAT-26 locus, single cell cloning produced several LNCaP subclones with alteration at 1 dinucleotide repeat. CONCLUSIONS: The well described prostate cancer cell line LNCaP has a mutation in the hMSH2 gene, resulting in loss of expression and possible evidence of microsatellite instability. To our knowledge our finding is the first demonstration of a genetic alteration in hMSH2 in a prostate cancer cell line. 相似文献
995.
996.
L Alder SJ Mercer NC Carter SK Toh BC Knight 《Annals of the Royal College of Surgeons of England》2021,103(3):180
IntroductionThe UK has an ageing population with an increased prevalence of frailty in the over 70s. Emergency laparotomy for acute intra-abdominal pathology is increasingly offered to this population. This can challenge decision making and information given to patients should not only be based on mortality outcomes but on relative expected quality of life and change to frailty syndromes.Materials and methodsThis was a single site National Emergency Laparotomy Audit (NELA)-based retrospective cohort audit for consecutive cases in the septuagenarian population assessing mortality, length of stay outcome and subjective postoperative functioning. Follow-up was conducted between one and two years postoperatively to determine this.ResultsSome 153 patients were identified throughout the single site NELA database. Median age was 79 years with a ratio of 1.7 men to women. Median rate of all-cause mortality was 35.3% at the median follow-up of 19 months. Median time from admission to death was 120 days. Of those who had died by the time of follow-up, significant preoperative indicators included clinical frailty scale (p < 0.0001), preoperative P-POSSUM (mortality). At follow-up, 35% responded to a quality of life follow-up. This revealed a decline in mid-term physical functioning, lower energy, higher fatigue and reduction in social functioning. There was also an increase in pre- and postoperative clinical frailty scale score.ConclusionIn the septuagenarian-plus population it is important to consider not only risk stratification with mortality scoring (P-POSSUM or NELA-adjusted risk), but to take into account frailty. Postoperative rehabilitation and careful recovery is paramount. Where possible, during the counselling and consent for emergency laparotomy, significant postoperative long-term deterioration in physical, emotional and social function should be considered. 相似文献
997.
V. Adusumalli N. Corkum A. Jacala T. Mukherjee D. Goodlett J. Crowther I. McConnell G. Goldstein 《Biopharmaceutics & drug disposition》1996,17(1):25-41
Pharmacokinetics and toxicokinetics of IRI-695, a tripeptide, were investigated in the rat, rabbit, dog, and monkey. Tissue distribution and excretion of [14C]IRI-695 were determined in the rat. Following a single intravenous (IV) injection, the elimination half-life (t1/2) of IRI-695 in the rabbit, dog, and monkey was similar (about 65 min) and approximately four times that in the rat (15 min). This difference in t1/2 can be attributed to about four times higher clearance of the drug in rats (11·2 mL min−1 kg −1). The volume of distribution (Vss) in these four species, 132–234 mL kg−1, suggested negligible preferential distribution of IRI-695 to body tissue. After a 5 mg kg−1 oral dose, the absolute bioavailability of IRI-695 was 2·0% in rats and 3·1% in dogs. However, systemic drug exposure in the dog was about five to 10 times that in the rat, which is related to the slower clearance of the peptide in the dog. Toxicokinetic studies in the rat and dog indicated linear kinetics and systemic exposure of IRI-695 up to 300 mg kg−1 d−1 oral doses throughout the 28 d toxicity study. Accumulation of the drug after the repeated oral dosing was negligible. After a single 0·10 mg kg−1 ]14C[IRI-695 IV injection in rats, almost all of the radioactivity administered was excreted in urine within 24 h postdose. 相似文献
998.
Contrast agent-enhanced, free-breathing, three-dimensional coronary magnetic resonance angiography. 总被引:3,自引:0,他引:3
M Stuber R M Botnar P G Danias M V McConnell K V Kissinger E K Yucel W J Manning 《Journal of magnetic resonance imaging : JMRI》1999,10(5):790-799
For free-breathing, high-resolution, three-dimensional coronary magnetic resonance angiography (MRA), the use of intravascular contrast agents may be helpful for contrast enhancement between coronary blood and myocardium. In six patients, 0.1 mmol/kg of the intravascular contrast agent MS-325/AngioMARK was given intravenously followed by double-oblique, free-breathing, three-dimensional inversion-recovery coronary MRA with real-time navigator gating and motion correction. Contrast-enhanced, three-dimensional coronary MRA images were compared with images obtained with a T2 prepulse (T2Prep) without exogenous contrast. The contrast-enhanced images demonstrated a 69% improvement in the contrast-to-noise ratio (6.6 +/- 1.1 vs. 11.1 +/- 2.5; P < 0.01) compared with the T2Prep approach. By using the intravascular agent, extensive portions (> 80 mm) of the native left and right coronary system could be displayed consistently with sub-millimeter in-plane resolution. The intravascular contrast agent, MS-325/AngioMARK, leads to a considerable enhancement of the blood/muscle contrast for coronary MRA compared with T2Prep techniques. The clinical value of the agent remains to be defined in a larger patient series. J. Magn. Reson. Imaging 1999;10:790-799. 相似文献
999.
1000.