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41.
Susan Redline Emma K Larkin Carolyn Kercsmar Melvin Berger Laura A Siminoff 《Annals of allergy, asthma & immunology》2003,90(5):516-528
BACKGROUND: The increasing morbidity attributable to asthma among school-aged children suggests the potential utility of school-based asthma screening programs. OBJECTIVE: We report our efforts to develop and validate culturally sensitive and clinically useful screening questionnaires (parent and child versions) for asthma and allergies among urban US school children. METHODS: Instrument development was accomplished through literature review, expert medical and child developmental input, focus group feedback, and a rigorous trial of the instruments in a public school setting. Questionnaires were distributed to 2,800 children and their families in an urban public school system (grades kindergarten through 6). Validity was evaluated by blinded comparison of results against a standardized clinical evaluation in 107 children, with final designations determined by an expert panel. RESULTS: Questionnaires pertaining to 2,083 children were returned (participation rate of 74%). A moderate level of agreement was observed between parent and student questionnaire responses (r values = 0.36 to 0.50; P values < 0.001). The highest frequency of asthma-like symptoms was reported for African-American boys and the lowest for Caucasian girls. The items from the parent questionnaire that best predicted asthma were "breathing problems" (occurring rarely or more; odds ratio 12.8; 95% confidence interval, 4.5 to 36.1) and "problems coughing" (sometimes or more; odds ratio 9.7; 95% confidence interval, 3.6 to 26.5). Considering the presence of cough (sometimes or more) and/or breathing problem (rarely or more) yielded a sensitivity of 80%; a specificity of 75%, a positive predictive value of 50%, and a negative predictive value of 92%. Similar levels of prediction were observed for the items "trouble breathing" and "noisy breathing" as directly reported by the students. Allergic rhinitis was best predicted by report of a runny/stuffy no se (sometimes or more; sensitivity of 83%, specificity of 61%).Allergic conjunctivitis was best predicted by "itchy eyes." CONCLUSIONS: Administration of a school-based questionnaire is feasible, with a high response rate and excellent internal consistency. A high sensitivity and acceptable specificity was achieved by using one to two questions for asthma, allergic rhinitis, and allergic conjunctivitis. Among the children in grades 2 or above, comparable levels of prediction could be achieved with the student or parent version. 相似文献
42.
Juan Tentoni Nélida Nora Polini Emma Beatriz Casanave 《Comparative clinical pathology》2008,17(3):193-196
The fibrinolytic mechanism in the armadillo Chaetophractus villosus (Mammalia, Xenarthra, Dasypodidae) quite unknown until now was studied. Results were compared with those corresponding to
healthy adult human beings. Whole blood lysis time and diluted blood lysis time were not detectable in armadillos. Euglobulin
clot lysis time and plasminogen activity (Plg) were lower than in healthy humans. We established the presence of the fibrinolytic
system in Ch. villosus through the measurement of fibrin fibrinogen degradation products. The activity of the plasminogen activator inhibitor was
two to four times greater than in healthy humans. The activity of the alpha 2 anti-plasmin (α2AP) was similar and displaced
toward lower values. The Plg/α2AP relation was lower. The results obtained suggest that Ch. villosus has a hypercoagulable and hypofibrinolytic profile. Our findings are not only the first contribution to elucidate the physiology
of the fibrinolytic system in Xenarthra but also contribute to develop an animal model for studies in haemostasis and thrombosis. 相似文献
43.
Palmieri EA Palmieri V Innelli P Arezzi E Ferrara LA Celentano A Fazio S 《European journal of applied physiology》2005,94(1-2):113-117
In older healthy men, aerobic exercise capacity is related to postischemic flow-mediated dilation of the brachial artery (FMD), but corresponding data in a younger population is not available. In addition, whether submaximal aerobic exercise performance also correlates with this kind of vasomotor reactivity is not known. Therefore, in 15 nonsmoking young healthy men [age 27 (5) years; body mass index: 24 (2) kg/m2; mean (SD)] with different levels of ordinary physical activity, but not performing upper-extremity training, we measured FMD at 1 min after reactive hyperemia, and pulmonary oxygen uptake (O2) at ventilatory anaerobic threshold (O2AT) and at peak effort (peak O2) during an incremental exercise on a treadmill. In our participants, FMD was 9.1 (3.4)%, O2AT was 40.72 (5.92) ml/kg per min, and peak O2 was 52.95 (8.13) ml/kg per min. Using bivariate Pearsons correlation, and in separate multivariate regression analyses, O2AT and peak VO2 showed a significant and reasonably good correlation with FMD (r=0.84, P<0.001 and r=0.77, P=0.001, respectively), independent of age, body mass index and serum total cholesterol (=0.77, P<0.001, R2 of the overall model=0.79 and =0.70, P<0.005, R2 of the overall model=0.69, respectively). Our data provide evidence suggesting that in young healthy men a higher submaximal and maximal aerobic exercise performance is associated with a greater FMD of peripheral conduit arteries. 相似文献
44.
The murine NF2 homologue encodes a highly conserved merlin protein with alternative forms 总被引:4,自引:1,他引:4
Haase Volker H.; Trofatter James A.; MacCollin Mla; Tarttelln Emma; Gusella James F.; Ramesh Vijaya 《Human molecular genetics》1994,3(3):407-411
The recently isolated gene for neuroflbromatosls type 2 (NF2)encodes a 595 amlno acid protein, named merlin, which Is relatedto the cytoskeleton-assoclated proteins moesln, ezrin and radlxin.To Identify evolutionarily conserved regions and to providesequence Information necessary for the establishment of a mousemodel for NF2, we have determined the cDNA sequence of the mouseNF2 tumor suppressor gene, and mapped It In the mouse genome.Mouse merlin is a 596 amino acid protein, 98% identical to humanmerlin, but one amlno acid longer due to the Insertion of aproline residue near the C-terminus. Of the nine amlno aciddifferences between mouse and humans, seven occur in the C-termlnal20% of the protein, far from the protein 4. 1 domain that definesthis family. Two of the NF2 cDNA clones reveal evidence of alternativesplicing events that alter the predicted merlin product, oneremoving a 45 amlno acid segment from the middle section ofthe protein and the other changing the C-terminus. The existenceof several different forms of merlin potentially with differentprimary roles will complicate the Identification of the precisefunction that must be disrupted to cause the NF2-assoclatedtumors. The mouse NF2 homologue maps to Chr 11, in a regionhomologous to human Chr 22, but devoid of any mouse mutationswhich could be models of the human disorder. 相似文献
45.
Janine M Prince Teresa C M Klinowska Emma Marshman Emma T Lowe Ulrike Mayer Jeff Miner Daniel Aberdam Dietmar Vestweber Barry Gusterson Charles H Streuli 《Developmental dynamics》2002,223(4):497-516
Epithelial cell survival is dependent on extracellular signals provided by both soluble factors and by adhesion. In the mammary gland, extensive apoptosis of epithelial cells occurs rapidly when lactation ceases, but the mechanism of apoptosis induction is not known. In tissue culture, mammary epithelial cells require laminin as a survival ligand and specific beta1 integrins are necessary to suppress apoptosis. To explore the possibility that dynamic changes in cell-matrix interactions contribute to the onset of apoptosis during mammary involution in vivo, a detailed immunohistochemical analysis of the expression of integrin subunits and their extracellular matrix ligands during mouse mammary gland development has been performed. The kinetics of apoptosis were determined by using tissue samples obtained from virgin, pregnant, lactating, and involuting gland. The maximal elevation of apoptosis occurred within 24 hr of weaning as determined by histologic analysis and caspase-3 staining. A wide variety of laminin subunits, together with nidogen-1 and -2, and perlecan were identified within the basement membrane region of epithelial ducts, lobules, and alveoli in both human and mouse mammary gland. However, no change in the distribution of any of the basement membrane proteins or their cognate integrin receptors was observed during the transition from lactation to apoptosis. Instead, we discovered that altered ligand-binding conformation of the beta1 integrin to a nonbinding state coincided with the immediate onset of mammary apoptosis. This finding may provide a novel dynamic mechanism for inhibiting the transduction of extracellular matrix survival signals, thereby contributing to the onset of apoptosis in a developmental context in vivo. 相似文献
46.
47.
48.
Qu CF Song EY Li Y Rizvi SM Raja C Smith R Morgenstern A Apostolidis C Allen BJ 《Clinical & experimental metastasis》2005,22(7):575-586
Purpose: The urokinase plasminogen activator (uPA) and its receptor (uPAR) are expressed by pancreatic cancer cells and can be targeted
by the plasminogen activator inhibitor type 2 (PAI2). We have labeled PAI2 with 213Bi to form the alpha conjugate (AC), and have studied its in vitro cytotoxicity and in vivo efficacy.
Methods and Materials: The expression of uPA/uPAR on pancreatic cell lines, human pancreatic cancer tissues, lymph node metastases, and mouse xenografts
were detected by immunohistochemistry, confocal microscopy, and flow cytometry. Cytotoxicity was assessed by the MTS and TUNEL
assay. At 2 days post-cancer cell subcutaneous inoculation, mice were injected with AC by local or systemic injection.
Results: uPA/uPAR is strongly expressed on pancreatic cancer cell lines and cancer tissues. The AC can target and kill cancer cells
in vitro in a concentration-dependent fashion. Some 90% of TUNEL positive cells were found after incubation with 1.2 MBq/ml of AC.
A single local injection of ~222 MBq/kg 2 days post-cell inoculation can completely inhibit tumor growth over 12 weeks, and
an intraperitoneal injection of 111 MBq/kg causes significant tumor growth delay.
Conclusions: 213Bi-PAI2 can specifically target pancreatic cancer cells in vitro and inhibit tumor growth in vivo. 213Bi-PAI2 may be a useful agent for the treatment of post-surgical pancreatic cancer patients with minimum residual disease. 相似文献
49.
Yeo GS Lank EJ Farooqi IS Keogh J Challis BG O'Rahilly S 《Human molecular genetics》2003,12(5):561-574
Mutations in the melanocortin-4 receptor gene (MC4R) represent the commonest monogenic cause of human obesity. However, information regarding the precise effects of such mutations on receptor function is very limited. We examined the functional properties of 12 different mutations in human MC4R that result in severe, familial, early-onset obesity. Of the nine missense mutants studied, four were completely unable to generate cAMP in response to ligand and five were partially impaired. Four showed evidence of impaired cell surface expression and six of reduced binding affinity for ligand. One mutation in the C-terminal tail, I316S, showed reduced affinity for alpha-MSH but retained normal affinity for the antagonist AgRP. None of the mutations inhibited signaling through co-transfected wild-type receptors. Thus, in the most comprehensive study to date of the functional properties of naturally occurring MC4R mutations we have (1) established that defective expression on the cell surface is a common mechanism impairing receptor function, (2) identified mutations which specifically affect ligand binding affinity thus aiding the definition of receptor structure-function relationships, (3) provided evidence against the notion that these receptor mutants act as dominant-negatives, and (4) identified a potentially novel molecular mechanism of receptor dysfunction whereby a mutation alters the relative affinities of a receptor for its natural agonist versus antagonist. 相似文献