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991.
Gallagher L Becker K Kearney G Dunlop A Stallings R Green A Fitzgerald M Gill M 《Journal of autism and developmental disorders》2003,33(1):105-108
Autism is a neurodevelopmental disorder presenting in the first 3 years of life. Deficits occur in the three core areas of communication, social interaction, and behavior. The causes of autism are unknown, but clinical genetic studies show strong evidence in favor of a genetic etiology. Molecular genetic studies report some association with candidate genes, and candidate regions have emerged from several genome-wide linkage studies. Here we report a clinical case of autism with a deletion on chromosome 2 in a young male with high-functioning autism. The deletion seems to correspond with regions emerging from linkage studies. We propose this as a possible candidate region in the search for autism genes. 相似文献
992.
Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids 总被引:16,自引:1,他引:15
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BACKGROUND: The debate as to whether asthma is a single or heterogeneous disease remains unresolved although pathological studies, mostly using fibreoptic bronchoscopy on small numbers of subjects, have emphasised the similarities between different clinical phenotypes. METHODS: Lower airway inflammation was assessed non-invasively using induced sputum in 34 normal controls and 259 adults with symptomatic asthma receiving treatment at steps 1-3 of the British Thoracic Society (BTS) guidelines. A subgroup of 49 patients treated with as required beta(2) agonists only who met BTS criteria for a step up in treatment were studied before and 2 months after treatment with inhaled budesonide 400 micro g twice daily. RESULTS: There was considerable heterogeneity in induced sputum cell counts, particularly in non-atopic patients. A subgroup of 60 patients had a distinctive sputum cell profile with a neutrophil count higher than our normal range (>65.3%) and a normal sputum eosinophil count (<1.9%). These patients were older, predominantly female, and were more likely to be non-atopic but otherwise had similar clinical and physiological features to the group as a whole. Among the 49 subjects studied before and after inhaled budesonide, 11 patients had an isolated sputum neutrophilia. Following treatment, these patients showed significantly less improvement in visual analogue symptom scores (-5.5 v -19.4 mm; mean difference 13.9; 95% CI 0.7 to 27.0), forced expiratory volume in 1 second (FEV(1)) (-0.08 v 0.13 l; mean difference 0.21; 95% CI 0.03 to 0.39), and concentration of methacholine provoking a fall in FEV(1) of 20% or more (PC(20)) (0.15 v 1.29 doubling doses; mean difference 1.11; 95% CI 0.13 to 2.15) than the remaining 38 patients. CONCLUSIONS: These results suggest the presence of a distinct subgroup of patients with mild to moderate asthma who have predominantly neutrophilic airway inflammation and who respond less well to treatment with inhaled corticosteroids. 相似文献
993.
Clinical and genetic epidemiology of inherited renal disease in Newfoundland. Newfoundland's geography, settlement, and socioeconomic development have produced a population useful for the study of genetic diseases. This review examines the clinical and genetic epidemiologic studies of inherited renal diseases undertaken in this population in the past 15 years. Common founder effects and large families through each generation provided very extensive pedigrees with autosomal-dominant diseases, such as polycystic kidney disease (PKD) and von Hippel-Lindau disease. In the former disease the diagnostic utility of renal ultrasound was determined, as was the prognostic impact of genotype, the role of the renin-angiotensin system in the pre-hypertensive phase, the potential for somatic mutations of the PKD2 gene, or the combination of mutations in the PKD1 and PKD2 genes, in single cells to induce cysts, and the demonstration that human transheterozygotes of PKD1 and -2 are not embryonically lethal. The presence of multiple genetic isolates and the high coefficient of kinship have predisposed to autosomal recessive diseases such as Bardet-Biedl syndrome (BBS), autosomal-recessive PKD, primary hyperoxaluria, and dihydroxyadenine urolithiasis. We have reported the clinical manifestations and natural history of the BBS, with particular emphasis on the fact that renal abnormalities are cardinal manifestations of the disease, the presence of at least six different genotypes, the identity and function of the BBS6 gene, and the presence of three different BBS6 mutations. Because of its relatively homogenous origins and high coefficient of kinship, Newfoundland's population also may be useful for the study of complex diseases such as preeclampsia. Using unbiased ascertainment and strict diagnostic criteria, we have found a significant risk of preeclampsia and non-proteinuric gestational hypertension in sisters of probands with preeclampsia, particularly when probands are defined by severity of preeclampsia, an observation that supports a study to search for susceptibility genes. We conclude that collaborations between clinical epidemiologists and molecular geneticists, using the Newfoundland population, have provided important clinical and mechanistic insights into inherited renal diseases. 相似文献
994.
Posttransplant lymphoproliferative disorders in liver transplantation: a 20-year experience 总被引:10,自引:0,他引:10
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Jain A Nalesnik M Reyes J Pokharna R Mazariegos G Green M Eghtesad B Marsh W Cacciarelli T Fontes P Abu-Elmagd K Sindhi R Demetris J Fung J 《Annals of surgery》2002,236(4):429-437
OBJECTIVE: To evaluate the incidence of posttransplant lymphoproliferative disease (PTLD) and the risk factors and the impact of this complication on survival outcomes in a large cohort of liver transplant recipients at a single institution. SUMMARY BACKGROUND DATA: Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, in large part due to the availability and reliance on the use of nonspecifically directed immunosuppression. However, as predicted and subsequently verified in 1968, an increased incidence of certain de novo malignancies has been observed, particularly with regards to lymphoid neoplasms. While many reports have confirmed and clarified the nature of PTLD, the literature is fraught with conflicting experience and outcomes with PTLD. METHODS: Four thousand consecutive patients who underwent liver transplants between February 1981 and April 1998 were included in this analysis and were followed to November 2001. The effect of recipient age at the time of transplant, recipient gender, diagnosis, baseline immunosuppression, grading of PTLD, and association with Epstein-Barr virus were compared. The causes of death were also examined. Treatment for PTLD varied over the 20-year period, but all included massive reduction or elimination of baseline immunosuppression. RESULTS: The 1-year patient survival for liver transplant patients with PTLD was 85%, while the overall patient survival for the entire cohort was 53%. The actuarial 20-year survival was estimated at 45%. The overall median time to PTLD presentation was 10 months, and children had an incidence of PTLD that was threefold higher than adults. Patient survival was better in children, in patients transplanted in the era of tacrolimus immunosuppression, in patients with polymorphic PTLD, and in those with limited disease. Interestingly, neither the presence or absence of Epstein-Barr virus nor the timing of PTLD presentation appeared to influence overall patient survival. Patients transplanted for alcohol-related liver disease had a similar incidence of PTLD but had a higher risk of mortality. CONCLUSIONS: While PTLD continues to pose problems in patients receiving liver transplants, improvements in patient survival have been observed over time. While it is too early to assess the impact of new advances in prophylaxis, diagnosis, and treatment, such approaches are based on an increased knowledge of the pathophysiology of PTLD. 相似文献
995.
The role of human-derived fibrin sealant in the reduction of postoperative flexor tendon adhesion formation in rabbits 总被引:8,自引:0,他引:8
Jones ME Burnett S Southgate A Sibbons P Grobbelaar AO Green CJ 《The Journal of hand surgery, European volume》2002,27(3):278-282
This study assessed the role of a novel fibrin sealant (Vivostat in adhesion reduction after flexor tendon surgery. The deep flexor tendons of the 2nd and 4th digits of the left paw of 20 rabbits were exposed and a standard partial injury was performed on each. The rabbits were randomized to either immediate post-injury treatment with Vivostat or no treatment. In each case active movement of the 2nd digit was prevented while the 4th digit was allowed to move normally. The two groups were assessed at 14 days for adhesion formation with a tensiometer. The right paw acted as the unoperated control. Results showed that there was no significant difference in the force needed to remove the tendon from its sheath when comparing the two Vivostat((R))-treated groups to the unoperated controls. There was, however, a highly significant difference in this force between the non-Vivostat-treated groups and the unoperated controls. This suggests a beneficial effect of Vivostat in reducing post surgical tendon adhesion formation. 相似文献
996.
Bell ML Davis D Cifuentes L Cohen A Gouveia N Grant L Green C Johnson T Rogat J Spengler J Thurston G 《Environmental health perspectives》2002,110(11):1163-1168
Forty-nine experts from 18 industrial and developing countries met on 6 September 2001 in Garmisch-Partenkirchen, Germany, to discuss the economic and public health impacts of air pollution, particularly with respect to assessing the public health benefits from technologies and policies that reduce greenhouse gas (GHG) emissions. Such measures would provide immediate public health benefits, such as reduced premature mortality and chronic morbidity, through improved local air quality. These mitigation strategies also allow long-term goals--for example, reducing the buildup of GHG emissions--to be achieved alongside short-term aims, such as immediate improvements in air quality, and therefore benefits to public health. The workshop aimed to foster research partnerships by improving collaboration and communication among various agencies and researchers; providing a forum for presentations by sponsoring agencies and researchers regarding research efforts and agency activities; identifying key issues, knowledge gaps, methodological shortcomings, and research needs; and recommending activities and initiatives for research, collaboration, and communication. This workshop summary briefly describes presentations made by workshop participants and the conclusions of three separate working groups: economics, benefits transfer, and policy; indoor air quality issues and susceptible populations; and development and transfer of dose-response relationships and exposure models in developing countries. Several common themes emerged from the working group sessions and subsequent discussion. Key recommendations include the need for improved communication and extended collaboration, guidance and support for researchers, advances in methods, and resource support for data collection, assessment, and research. 相似文献
997.
Despite mounting evidence on butyltin (BT) contamination and related immunotoxic effects on wildlife, very little is known about BT-associated immunotoxic effects on humans, particularly the effects on human natural killer (NK) lymphocyte function. Our earlier studies demonstrated that in vitro exposure to environmentally relevant concentrations of BTs negatively affect human NK cells and that there are measurable levels of BTs in human blood. In this study we examined whether the inhibition of NK cell cytotoxic function induced by a brief exposure (1 h) to BTs is reversible when the cells are allowed to recover in BT-free media for up to 6 days. Standard methods were used in chemical preparation, blood sampling, NK cell isolation, and 51-Chromium release assay. The results revealed that exposure to 300 nM TBT for 1 h caused an approximately 65- decrease in NK cytotoxic function, whether the lymphocytes were given as long as a 6-day recovery period or no recovery period. There was no recovery (nor any further loss) of NK cytotoxic function following removal of the compound. Exposure to 5 microM DBT for 1 h showed a 41% decrease in cytotoxic function with 0-h recovery and an 83% decrease after a 24-h recovery period. Thus, not only is there no significant recovery of NK cytotoxic function when the lymphocytes are allowed to incubate in BT-free medium for up to 6 days but there is additional loss of cytotoxic function. The results indicated that short-term exposure to BTs causes persistent negative effects on NK cell ability to kill cancer cells. 相似文献
998.
Cytotoxic function of human natural killer (NK) cells is modulated by a variety of cytokines. Interleukins (IL) 2 and 12 are both potent stimulators of NK cell cytotoxic function. Tributyltin (TBT) is used in a variety of consumer products and industrial applications. TBT is found in dairy products, meat, and fish. We and others have shown that there are measurable levels of TBT in human blood. Butyltins appear to increase the risk of cancer and viral infections in exposed individuals. We have demonstrated that the ability of NK cells to kill tumor cells is greatly diminished after a l-h exposure to TBT and that this inhibition persists even after removal of the compound. In the current study we examine the effects of the NK-stimulatory ILs, IL2 and IL12, on the ability of NK cells to recover from the persistent inhibitory effects of a 1-h TBT treatment. Highly purified NK cells (> 95% CD16(+)) or a lymphocyte preparation containing both T lymphocytes and NK cells were treated with 300 nM TBT and then allowed to recover for 24 h, 48 h, 4 days, and 6 days in TBT-free media containing no interleukin, 1000 U/mL IL2, 20 ng/mL IL l2, or a combination of IL2 plus IL12. Tumor killing function was then tested using a radioactive chromium release assay. As seen in our previous studies there is no recovery of NK cell cytotoxic function even after a 6-day recovery period when no interleukin is present in the medium. However, there is significant recovery of NK cytotoxic function when IL2, IL12, or the combination of IL2 plus IL12 is present in the medium during the recovery period. 相似文献
999.
1000.
Leem JY Saura CA Pietrzik C Christianson J Wanamaker C King LT Veselits ML Tomita T Gasparini L Iwatsubo T Xu H Green WN Koo EH Thinakaran G 《Neurobiology of disease》2002,11(1):64-82
Presenilin 1 (PS1) and presenilin 2 play a critical role in the gamma-secretase processing of amyloid precursor protein (APP) and Notch1. Here, we investigate maturation and intracellular trafficking of APP and other membrane proteins in cells expressing an experimental PS1 deletion mutant (deltaM1,2). Stable expression of deltaM1,2 impairs gamma-secretase processing of Notch1 and delays Abeta secretion. Kinetic studies show enhanced O-glycosylation and sialylation of holo-APP and marked accumulation of APP COOH-terminal fragments (CTFs). Surface biotinylation, live staining, and trafficking studies show increased surface accumulation of holo-APP and CTFs in deltaM1,2 cells resulting from enhanced surface delivery of newly synthesized APP. Expression of a loss-of-function PS1 mutant (D385A) or incubation of cells with gamma-secretase inhibitors also increases surface levels of holo-APP and CTFs. In contrast to APP, glycosylation and surface accumulation of another type I membrane protein, nicastrin, are markedly reduced in deltaM1,2 cells. Finally, expression of deltaM1,2 results in the increased assembly and surface expression of nicotinic acetylcholine receptors, illustrating that PS1's influence on protein trafficking extends beyond APP and other type I membrane protein substrates of gamma-secretase. Collectively, our findings provide evidence that PS1 regulates the glycosylation and intracellular trafficking of APP and select membrane proteins. 相似文献