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31.
K G Monaghan W E Highsmith J Amos V M Pratt B Roa M Friez L L Pike-Buchanan I M Buyse J B Redman C M Strom A L Young W Sun 《Genetics in medicine》2004,6(5):421-425
PURPOSE: We expect that the mutation panel currently recommended for preconception/prenatal CF carrier screening will be modified as new information is learned regarding the phenotype associated with specific mutations and allele frequencies in various populations. One such example is the I148T mutation, originally described as a severe CF mutation. After implementation of CF population-based carrier screening, we learned that I148T exists as a complex allele with 3199del6 in patients with clinical CF, whereas asymptomatic compound heterozygotes for I148T and a second severe CF mutation were negative for 3199del6. METHODS: We performed reflex testing for 3199del6 on 663 unrelated specimens, including I148T heterozygotes, compound heterozygotes, and a homozygous individual. RESULTS: Less than 1% of I148T carriers were also positive for 3199del6. Excluding subjects tested because of a suspected or known CF diagnosis or positive family history, 0.6% of I148T-positive individuals were also positive for 3199del6. We identified 1 I148T homozygote and 6 unrelated compound heterozygous individuals with I148T and a second CF variant (2 of whom also carried 3199del6). In addition, one fetus with echogenic bowel and one infertile male were heterozygous for I148T (3199del6 negative). CONCLUSIONS: Reflex testing for 3199del6 should be considered whenever I148T is identified. Reflex testing is of particular importance for any symptomatic patient or whenever one member of a couple carries a deleterious CF mutation and the other member is an I148T heterozygote. Further population data are required to determine if I148T, in the absence of 3199del6, is associated with mild or atypical CF or male infertility. 相似文献
32.
Heterotrimeric G proteins and the platelet-derived growth factor receptor-beta contribute to hypoxic proliferation of smooth muscle cells 总被引:1,自引:0,他引:1
Lannér MC Raper M Pratt WM Rhoades RA 《American journal of respiratory cell and molecular biology》2005,33(4):412-419
Hypoxic proliferation of pulmonary arterial smooth muscle cells (PASMC) is mitogen dependent, but the signaling pathways mediating hypoxia-induced cell growth are not well understood. We investigated hypoxic proliferation in primary cultures from porcine pulmonary artery smooth muscle. The cells were grown in medium with or without platelet-derived growth factor (PDGF)-B, a potent smooth muscle cell mitogen. Hypoxia induced upregulation of PDGF receptor-beta expression, the primary receptor for PDGF-B. However, PDGF-B-mediated hypoxic enhancement of proliferation was abolished by pertussis toxin, indicating (1) involvement of heterotrimeric Galpha i proteins and (2) minimal effect of increased PDGF receptor expression in hypoxic enhancement of proliferation. We treated PASMC with labeled, nonhydrolyzable analogs of GTP to determine directly if GTP binding proteins were activated by hypoxia in PASMC. We show that hypoxia stimulates GTP incorporation in PASMC both in the presence and absence of PDGF-B. Serum-starved PASMC are able to increase their incorporation of GTP after only 10 min of hypoxia, and this response is not pertussis toxin sensitive. In serum-starved PASMC, we show that hypoxia stimulates incorporation of GTP into a 44-kD protein. The results show that heterotrimeric G proteins are involved in hypoxia-induced signaling in pulmonary vascular smooth muscle cells. 相似文献
33.
1. A constant specific activity of radioactively labelled amino acids was maintained in the circulation by means of a new technique devised for this purpose. This has made it possible to measure accurately the entry rates of amino acids into the brain in vivo. 2. The rates of entry into the brain of seven nutritionally non-essential amino acids were measured. 3. Glycine and proline enter the brain relatively slowly, at rates comparable to those of amino acids which are not normally found in the blood. Thus their entry is due mainly if not entirely to passive diffusion. 4. Serine (which is used by the brain to make glycine) and alanine (which is used to make glutamate and aspartate) enter the brain as rapidly as the essential amino acids and thus, although not essential for the body as a whole, appear to be essential for the brain. 5. It is suggested that those amino acids that the brain is able to synthesize have low rates of entry, even though they are present at high concentrations in the plasma, but that the transport systems for those amino acids that are not synthesized in the brain ensure rapid entry at rates that are related to the rates of cerebral utilization. 相似文献
34.
Circulating lymphocyte populations and autoantibodies in non-obese diabetic (NOD) mice: a longitudinal study. 总被引:1,自引:5,他引:1 下载免费PDF全文
O Pontesilli P Carotenuto L S Gazda P F Pratt S J Prowse 《Clinical and experimental immunology》1987,70(1):84-93
Several previous observations indicate a role for the immune system in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice. In order to assess the status of the immune system in this model of spontaneous diabetes we studied the phenotype of circulating lymphocytes and the humoral autoimmunity to islet cells in non-diabetic NOD mice at various ages. Lymphocyte numbers were low in young NOD mice (age less than 160 days) as compared with other strains of mice and increased later to reach values in or above the range of controls. The percentages of circulating T lymphocytes and their L3T4+ and Lyt2+ subsets were higher in NOD mice of all ages and both sexes than in controls; however, no imbalance of the L3T4+ and Lyt2+ subpopulations was found. Anti-insulin autoantibodies were detected by an ELISA assay in all the NOD mice studied throughout the entire period of observation. Autoantibodies reacting with the cytoplasm of islet cells in Bouin's fixed pancreas sections, likely to be anti-insulin antibodies, were found in 47 to 58% of the samples from NOD mice aged 75 to 150 days. Antibodies to surface antigens of rat insulinoma cells were virtually absent in young NOD mice (75-100 days) and appeared in 33 to 43% of the samples from 150 to 185 days old NOD mice. The autoantibodies and the quantitative lymphocyte abnormalities reported here, although not predictive of the appearance of overt diabetes, are likely to be involved in the pathogenesis of the disease and therefore may indicate directions for future investigations. 相似文献
35.
The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission 总被引:2,自引:5,他引:2
Murray A; Macpherson JN; Pound MC; Sharrock A; Youings SA; Dennis NR; McKechnie N; Linehan P; Morton NE; Jacobs PA 《Human molecular genetics》1997,6(2):173-184
Factors involved in the stability of trinucleotide repeats during
transmission were studied in 139 families in which a full mutation,
premutation or intermediate allele at either FRAXA or FRAXE was
segregating. The transmission of alleles at FRAXA, FRAXE and four
microsatellite loci were recorded for all individuals. Instability within
the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for
FRAXE) was extremely rare; only one example was observed, an increased in
size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in
the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were
unstably transmitted. Instability was more frequent for FRAXA intermediate
alleles that had a tract of pure CGG greater than 37 although instability
only occurred in two of 13 such transmissions: the changes observed were
limited to only one or two repeats. Premutation FRAXA alleles over 100
repeats expanded to a full mutation during female transmission in 100% of
cases, in agreement with other published series. There was no clear
correlation between haplotype and probability of expansion of FRAXA
premutations. Instability at FRAXA or FRAXE was more often observed in
conjunction with a second instability at an independent locus suggesting
genomic instability as a possible mechanism by which at least some FRAXA
and FRAXE mutations arise.
相似文献
36.
Cross-correlation of EMG reveals widespread synchronization of motor units during some slow movements in intact cats 总被引:1,自引:0,他引:1
G E Loeb W J Yee C A Pratt C M Chanaud F J Richmond 《Journal of neuroscience methods》1987,21(2-4):239-249
It is commonly assumed that the motor units comprising a single mammalian muscle will be recruited asynchronously at subtetanic firing rates to produce smoothly modulated force output. However, electromyograms from certain neck muscles, recorded by implanted bipolar "patch" electrodes having large contacts, often exhibited a rhythmic clustering of spike activity whose patterns suggested that motor-unit firing was synchronized both within and across muscles. We have developed a computerized processing system that digitizes EMG activity and calculates auto- and cross-correlation products of selected segments. The presence or absence of synchronization caused by neural mechanisms can be identified and differentiated from that due to the rhythmicity of the behavior itself (e.g. shaking) or due to cross-talk, according to the shapes of the resultant correlograms. These methods have so far been applied to the study of hindlimb and neck muscle EMG during various natural motor behaviors, but they provide a general, quantitative tool for the study of an important aspect of motor control that may be overlooked by conventional sampling and smoothing techniques. 相似文献
37.
Effects of diquat on freshwater microbial communities 总被引:3,自引:0,他引:3
A. L. Melendez R. L. Kepner Jr. J. M. Balczon J. R. Pratt 《Archives of environmental contamination and toxicology》1993,25(1):95-101
A static microcosm system was used to evaluate effects of the herbicide diquat (0.3–30 mg/L) on the structure and function of naturally derived microbial communities on polyurethane foam substrates. Microbial communities were exposed to a single application of diquat and were monitored for 21 days. Effects on community structure included changes in algal cell density at diquat concentrations 0.3 mg/L (after an initial decrease in net productivity), bacterial cell density (1 mg/L diquat), and increased biomass accumulation (10 and 30 mg/L diquat). The species richness of protozoa was reduced at diquat concentrations >0.3 mg/L; protozoan species composition was progressively more dissimilar with diquat treatment. Effects on community function included inhibition of net productivity and community respiration (10 and 30 mg/L diquat), and decreased enzyme activities [alkaline phosphatase (1, 10, and 30 mg/L diquat), electron transport system (0.3 mg/L diquat), and -glucosidase (0.3 mg/L diquat)]. Both photosynthetic and nonphotosynthetic organisms were affected by diquat. Most structural and functional responses were sensitive indicators of stress. Estimated chronic toxicity values ranged from 0.3 mg/L (day 3) to 5.5 mg/L (day 21). Most microbial responses indicated that microbial community structure and function did not recover within the 21-day exposure period. 相似文献
38.
Keller MB Yonkers KA Warshaw MG Pratt LA Gollan JK Massion AO White K Swartz AR Reich J Lavori PW 《The Journal of nervous and mental disease》1994,182(5):290-296
This article reports on the course of uncomplicated panic disorder and panic with agoraphobia on 309 patients participating in the Harvard/Brown Anxiety Research Project, a prospective longitudinal study of patients with DSM-III-R-defined anxiety disorders. At 1 year, there was a .39 probability of full remission for uncomplicated panic disorder and a .17 probability of full remission for panic disorder with agoraphobia Similar differences in time to remission for these syndromes were still found when criteria for remission were made less stringent. However, even requiring less improvement for remission left a large percentage of subjects in an episode, and for those that remitted, relapse occurred quickly, indicating a chronic and recurrent course of illness. This is the first longitudinal, prospective, naturalistic study on a large cohort of subjects with anxiety disorders to have regular, structured, short-interval follow-up. Our results are consistent with the view that panic disorder has a chronic course with high rates of relapse after remission and longer episodes when agoraphobia is a part of the constellation of symptoms. 相似文献
39.
Interactive risk factors for treatment adherence in a chronic psychotic disorders population 总被引:4,自引:0,他引:4
This study identified the unique and primary contributions of several concurrent risk factors for poor adherence to treatment recommendations in a clinic population of individuals with chronic psychotic disorders, i.e. 48% had DSM-IV diagnoses of schizoaffective disorder, 38% had schizophrenia, paranoid type, 12% had schizophrenia, undifferentiated type, and 2% had affective disorder with psychotic features. The target cohort consisted of 87 consecutive admissions to a continuing day treatment program. As part of a services-oriented quality assurance program, clinical staff completed rating scales for all patients. These included the BASIS-32 rating scale, which consisted of the following five subscales: psychosis; depression/anxiety; impulsive/addictive behavior; relation to self and others; and daily living and role functioning, and the Working Alliance Inventory-short form (therapist version), which consisted of the following three subscales: goal; task; and bond. These data were used to identify risk factors that weaken a patient's adherence to medication and non-medication treatment during the first 2 weeks of treatment in the clinic. Medication treatment consisted of both typical and atypical neuroleptic medications, with most patients being on multiple medications. Correlational analyses suggested that many of the risk factor variables were significantly associated with poor treatment adherence. Regression analyses suggested that the degree of psychoticism was most strongly associated with poor adherence to medication treatment and that difficulties relating to self and others were the strongest predictor of poor adherence to non-medication treatment. A large-sample services research design such as this can begin to determine patterns of associations between previous identified risk factors and poor treatment adherence in individuals with chronic psychotic disorders. 相似文献
40.
Hymas DC Mamalis N Pratt DV Scott MH Anderson RL Langer PD 《Ophthalmic plastic and reconstructive surgery》1999,15(2):139-142
PURPOSE: To describe a 14-year-old boy with a 1-month history of a rapidly growing, nontender, lower eyelid mass. METHODS: The specimen was studied using light microscopy. RESULTS: Although magnetic resonance imaging suggested a chronic vascular lesion, histopathologic analysis after excisional biopsy was consistent with nodular fasciitis. CONCLUSIONS: Nodular fasciitis is a relatively common soft-tissue lesion and represents a benign, reactive process. Lesions in the head and neck develop more frequently in children and adolescents than in adults, but periorbital lesions are uncommon. This is the first reported case of nodular fasciitis of the lower eyelid in a pediatric patient. 相似文献