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81.
Familial and genetic aspects of spondyloarthropathy 总被引:5,自引:0,他引:5
Breban M Said-Nahal R Hugot JP Miceli-Richard C 《Rheumatic Diseases Clinics of North America》2003,29(3):575-594
Predisposition to SpA is largely determined by genetic factors including HLA-B27 and other as yet unknown genes that might be tracked by a positional cloning approach. Analysis performed on a large cohort of SpA multiplex families revealed that the different articular and extra-articular inflammatory manifestations comprising the SpA spectrum were linked together, implying that they were determined by a shared set of factors, including HLA-B27. The variety of phenotypes appeared to be related to ubiquitous and secondary factors. Hence, SpA appeared to be more homogenous than previously thought and should be regarded as a unique disease. This conclusion also implies that genetic studies should be performed on the whole group. Such an approach allowed identification of HLA-DR4 as a gene contributing to SpA predisposition independently of linkage disequilibrium with HLA-B27. A significant role for CARD15/NOD2 gene in predisposition to SpA was ruled out, in agreement with the hypothesis that the inflammatory bowel disease in SpA is determined by factors different than those responsible for isolated Crohn's disease. 相似文献
82.
Watterberg KL Shaffer ML Garland JS Thilo EH Mammel MC Couser RJ Aucott SW Leach CL Cole CH Gerdes JS Rozycki HJ Backstrom C 《The Journal of clinical endocrinology and metabolism》2005,90(12):6380-6385
CONTEXT: Various cosyntropin doses are used to test adrenal function in premature infants, without consensus on appropriate dose or adequate response. OBJECTIVE: The objective of this study was to test the cortisol response of extremely low birth weight infants to different cosyntropin doses and evaluate whether these doses differentiate between groups of infants with clinical conditions previously associated with differential response to cosyntropin. DESIGN: The design was a prospective, nested study conducted within a randomized clinical trial of low-dose hydrocortisone from November 1, 2001, to April 30, 2003. SETTING: The setting was nine newborn intensive care units. PATIENTS: The patients included infants with 500-999 g birth weight. INTERVENTION: The drug used was cosyntropin, at 1.0 or 0.1 microg/kg, given between 18 and 28 d of birth. MAIN OUTCOME MEASURE: We measured the cortisol response to cosyntropin. RESULTS: Two hundred seventy-six infants were tested. Previous hydrocortisone treatment did not suppress basal or stimulated cortisol values. Cosyntropin, at 1.0 vs. 0.1 microg/kg, yielded higher cortisol values (P < 0.001) and fewer negative responses (2 vs. 21%). The higher dose, but not the lower dose, showed different responses for girls vs. boys (P = 0.02), infants receiving enteral nutrition vs. not (P < 0.001), infants exposed to chorioamnionitis vs. not (P = 0.04), and those receiving mechanical ventilation vs. not (P = 0.02), as well as a positive correlation with fetal growth (P = 0.03). A response curve for the 1.0-microg/kg dose for infants receiving enteral nutrition (proxy for clinically well infants) showed a 10th percentile of 16.96 microg/dl. Infants with responses less than the 10th percentile had more bronchopulmonary dysplasia and longer length of stay. CONCLUSIONS: A cosyntropin dose of 0.1 microg/kg did not differentiate between groups of infants with clinical conditions that affect response. We recommend 1.0 microg/kg cosyntropin to test adrenal function in these infants. 相似文献
83.
Reengineered salivary glands are stable endogenous bioreactors for systemic gene therapeutics 总被引:7,自引:0,他引:7 下载免费PDF全文
Voutetakis A Kok MR Zheng C Bossis I Wang J Cotrim AP Marracino N Goldsmith CM Chiorini JA Loh YP Nieman LK Baum BJ 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(9):3053-3058
The use of critical-for-life organs (e.g., liver or lung) for systemic gene therapeutics can lead to serious safety concerns. To circumvent such issues, we have considered salivary glands (SGs) as an alternative gene therapeutics target tissue. Given the high secretory abilities of SGs, we hypothesized that administration of low doses of recombinant adeno-associated virus (AAV) vectors would allow for therapeutic levels of transgene-encoded secretory proteins in the bloodstream. We administered 10(9) particles of an AAV vector encoding human erythropoietin (hEPO) directly to individual mouse submandibular SGs. Serum hEPO reached maximum levels 8-12 weeks after gene delivery and remained relatively stable for 54 weeks (longest time studied). Hematocrit levels were similarly increased. Moreover, these effects proved to be vector dose-dependent, and even a dosage as low as 10(8) particles per animal led to significant increases in hEPO and hematocrit levels. Vector DNA was detected only within the targeted SGs, and levels of AAV copies within SGs were highly correlated with serum hEPO levels (r = 0.98). These results show that SGs appear to be promising targets with potential clinical applicability for systemic gene therapeutics. 相似文献
84.
Coyle YM Aragaki CC Hynan LS Gruchalla RS Khan DA 《Archives of internal medicine》2003,163(13):1591-1596
BACKGROUND: Acute asthma often requires expensive emergency department visits and hospitalizations, especially among economically disadvantaged inner-city adults. However, few studies have examined approaches for improving acute asthma care in this population. METHODS: We conducted a cohort study involving patients who were discharged from a public hospital emergency department following acute asthma care between March 31, 1997, and August 5, 1999, to identify processes of care effective for improving peak expiratory flow rate at a 2- to 3-week follow-up. Adult patients who met the predetermined criteria for asthma, who underwent a baseline peak expiratory flow rate reading, and who did not have concurrent acute sinusitis or pneumonia were eligible (N = 448). Of the 365 patients enrolled in the study, 309 (84.7%) completed it. We used a multiple linear regression analysis adjusted for patient risk to assess the association between acute asthma care processes derived from the National Asthma Education Prevention Program guidelines (inhaled beta2-agonists, inhaled corticosteroids, systemic corticosteroids, asthma care follow-up, and patient asthma education) and percentage peak expiratory flow rate change at follow-up. RESULTS: Systemic corticosteroids had a significant effect for increasing percentage peak expiratory flow rate change at the 2- to 3-week follow-up for all asthma exacerbation severity levels (beta = 26.1; 95% confidence interval, 1.8-50.5; P =.04) and severity levels specified by the National Asthma Education Prevention Program guidelines (beta = 31.6; 95% confidence interval, 8.1-55.1; P =.01). CONCLUSION: Outpatient systemic corticosteroids were effective for improving lung function 2 to 3 weeks after acute asthma care, and their use should reduce asthma-related morbidity, especially among economically disadvantaged inner-city adults. 相似文献
85.
86.
Rahul S. Bhansali Malini Rammohan Paul Lee Anouchka P. Laurent Qiang Wen Praveen Suraneni Bon Ham Yip Yi-Chien Tsai Silvia Jenni Beat Bornhauser Aurlie Siret Corinne Fruit Alexandra Pacheco-Benichou Ethan Harris Thierry Besson Benjamin J. Thompson Young Ah Goo Nobuko Hijiya Maria Vilenchik Shai Izraeli Jean-Pierre Bourquin Sbastien Malinge John D. Crispino 《The Journal of clinical investigation》2021,131(1)
87.
Holly Turula Corinne J. Smith Finn Grey Katherine A. Zurbach Christopher M. Snyder 《European journal of immunology》2013,43(5):1252-1263
Both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) establish persistent infections that induce the accumulation of virus‐specific T cells over time in a process called memory inflation. It has been proposed that T cells expressing T‐cell receptors (TCRs) with high affinity for HCMV‐derived peptides are preferentially selected after acute HCMV infection. To test this in the murine model, small numbers of OT‐I transgenic T cells, which express a TCR with high affinity for the SIINFEKL peptide, were transferred into congenic mice and recipients were challenged with recombinant MCMV expressing SIINFEKL. OT‐I T cells were selectively enriched during the first 3 weeks of infection. Similarly, in the absence of OT‐I T cells, the functional avidity of SIINFEKL‐specific T cells increased from early to late times postinfection. However, even when exceedingly small numbers of OT‐I T cells were transferred, their inflation limited the inflation of host‐derived T cells specific for SIINFEKL. Importantly, subtle minor histocompatibility differences led to late rejection of the transferred OT‐I T cells in some mice, which allowed host‐derived T cells to inflate substantially. Thus, T cells with a high functional avidity are selected shortly after MCMV infection and continuously sustain their clonal dominance in a competitive manner. 相似文献
88.
Florence Suy Anne Carricajo Florence Grattard Céline Cazorla Corinne Denis Philippe Girardin Frédéric Lucht Elisabeth Botelho-Nevers 《Journal of clinical microbiology》2013,51(9):3154-3156
Mycobacterium thermoresistibile is a rapidly growing environmental nontuberculous mycobacterium, seldom reported in human infections. Here, we describe a rare case of tibial-nail-related osteomyelitis due to Mycobacterium thermoresistibile. We also review the literature about the infections caused by this pathogen. 相似文献
89.
Browne Julia Cather Corinne Zvonar Vanya Thayer Katherine Skiest Hannah Arntz Diana Kritikos Katherine Schnitzer Kristina Brown Hannah Evins A. Eden Donovan Abigail 《Community mental health journal》2021,57(5):864-871
Community Mental Health Journal - The mortality disparity for persons with schizophrenia spectrum disorders (SSDs) due to cardiovascular disease is a devastating problem. Many risk factors are... 相似文献
90.
Laure Ségurel Frederic Austerlitz Bruno Toupance Mathieu Gautier Joanna L Kelley Patrick Pasquet Christine Lonjou Myriam Georges Sarah Voisin Corinne Cruaud Arnaud Couloux Tatyana Hegay Almaz Aldashev Renaud Vitalis Evelyne Heyer 《European journal of human genetics : EJHG》2013,21(10):1146-1151
The high prevalence of type 2 diabetes and its uneven distribution among human populations is both a major public health concern and a puzzle in evolutionary biology. Why is this deleterious disease so common, while the associated genetic variants should be removed by natural selection? The ‘thrifty genotype'' hypothesis proposed that the causal genetic variants were advantageous and selected for during the majority of human evolution. It remains, however, unclear whether genetic data support this scenario. In this study, we characterized patterns of selection at 10 variants associated with type 2 diabetes, contrasting one herder and one farmer population from Central Asia. We aimed at identifying which alleles (risk or protective) are under selection, dating the timing of selective events, and investigating the effect of lifestyle on selective patterns. We did not find any evidence of selection on risk variants, as predicted by the thrifty genotype hypothesis. Instead, we identified clear signatures of selection on protective variants, in both populations, dating from the beginning of the Neolithic, which suggests that this major transition was accompanied by a selective advantage for non-thrifty variants. Combining our results with worldwide data further suggests that East Asia was particularly prone to such recent selection of protective haplotypes. As much effort has been devoted so far to searching for thrifty variants, we argue that more attention should be paid to the evolution of non-thrifty variants. 相似文献