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101.
We investigated the distribution of natural killer (NK) cell subsets, their activating and inhibitory receptors, and their cytolytic potential, in primary human immunodeficiency virus (HIV)-infected (PHI) individuals at baseline and during 1 year of follow-up with or without antiretroviral therapy, and compared the results with those obtained in treatment-naïve, chronically HIV-infected (CHI) individuals, and HIV-seronegative (HN) healthy individuals. The proportion of the CD56dim and CD56bright subsets decreased with disease progression, whereas that of the CD56− CD16+ subset increased. In the CD56dim subset, the proportion of cells with natural cytotoxicity receptors (NCRs) decreased with disease progression, and their cytolytic potential was reduced. Conversely, the CD56bright subset was characterized by a high proportion of NCR-positive, killer cell immunoglobulin-like receptor (KIR)-positive NKG2A+ cells in both CHI and PHI individuals, which was associated with an increase in their cytolytic potential. During the 1 year of follow-up, the PHI individuals with high viraemia levels and low CD4+ T-cell counts who received highly active antiretroviral therapy (HAART) had a similar proportion of NK subsets to CHI individuals, while patients with low viraemia levels and high CD4+ T-cell counts who remained untreated had values similar to those of the HN individuals. Our results indicate a marked perturbation of the NK cell compartment during HIV-1 infection that is multifaceted, starts early and is progressive, primarily involves the CD56bright subset, and is partially corrected by effective HAART. 相似文献
102.
S Accordini AG Corsico M Braggion MW Gerbase D Gislason A Gulsvik J Heinrich C Janson D Jarvis R Jõgi I Pin Y Schoefer M Bugiani L Cazzoletti I Cerveri A Marcon R de Marco 《International archives of allergy and immunology》2012,160(1):93-101
Background: This study is aimed at providing a real-world evaluation of the economic cost of persistent asthma among European adults according to the degree of disease control [as defined by the 2006 Global Initiative for Asthma (GINA) guidelines]. Methods: A prevalence-based cost-of-illness study was carried out on 462 patients aged 30-54 years with persistent asthma (according to the 2002 GINA definition), who were identified in general population samples from 11 European countries and examined in clinical settings in the European Community Respiratory Health Survey II between 1999 and 2002. The cost estimates were computed from the societal perspective following the bottom-up approach on the basis of rates, wages and prices in 2004 (obtained at the national level from official sources), and were then converted to the 2010 values. Results: The mean total cost per patient was EUR 1,583 and was largely driven by indirect costs (i.e. lost working days and days with limited, not work-related activities 62.5%). The expected total cost in the population aged 30-54 years of the 11 European countries was EUR 4.3 billion (EUR 19.3 billion when extended to the whole European population aged from 15 to 64 years). The mean total cost per patient ranged from EUR 509 (controlled asthma) to EUR 2,281 (uncontrolled disease). Chronic cough or phlegm and having a high BMI significantly increased the individual total cost. Conclusions: Among European adults, the cost of persistent asthma drastically increases as disease control decreases. Therefore, substantial cost savings could be obtained through the proper management of adult patients in Europe. 相似文献
103.
Jessica Goodkind Marianna LaNoue Christopher Lee Lance Freeland Rachel Freund 《Journal of community psychology》2012,40(4):468-478
An important predictor of youth well‐being and resilience is the presence of nurturing adults in a youth's life. Parents are ideally situated to fulfill this role but often face challenges and stressors that impede their ability to provide adequate support and guidance. American Indian parents may also be affected by intergenerational transmission of trauma and loss of traditional parenting practices, as a result of forced boarding school and/or relocation. Members of a community‐university partnership sought to interrupt cycles of violence and poor mental health of youth through a culturally‐grounded intervention for youth and their parents that focused on healing historical trauma, strengthening positive parenting practices and social skills, reconnecting to traditional cultural knowledge, and improving parent‐child relationships/communication. This article describes parental involvement and its challenges and provides mixed‐method results for 10 parents related to enculturation, parenting practices, parent‐child communication, family cohesion, historical loss and associated symptoms, and community involvement. 相似文献
104.
Orlando G Gabriella O Guaraldi G Giovanni G Zona S Stefano Z Carli F Federica C Bagni P Pietro B Menozzi M Marianna M Cocchi S Stefania C Scaglioni R Riccardo S Ligabue G Guido L Raggi P Paolo R 《Journal of acquired immune deficiency syndromes (1999)》2012,59(5):494-497
Epicardial Adipose Tissue (EAT) has been associated with adverse cardiovascular events in the general population. We studied the association of general adiposity measures (body mass index, waist circumference) and ectopic adipose tissue [visceral adipose tissue (VAT); liver fat (LF); EAT) with prevalent cardiovascular disease (CVD) (prior myocardial infarction, coronary revascularization, stroke, peripheral vascular disease] in 583 HIV-infected men. VAT, EAT, and LF (liver/spleen attenuation ratio < 1.1) were measured by computed tomography. Patients' mean age was 48.5 ± 8.1 years, prior CVD was present in 33 (5.7%) patients. Factors independently associated with CVD on multivariable analyses were age [incidence-rate ratio (IRR) = 1.07, 95% confidence interval (CI): 1.02 to 1.12], smoking (IRR = 2.70, 95% CI: 1.22 to 6.01), Center for Disease Control group C (IRR = 3.09, 95% CI: 1.41 to 6.76), EAT (IRR = 1.13, 95% CI: 1.04 to 1.24, per 10 cm), LF (IRR = 1.17, 95% CI: 1.04 to 1.32), and VAT (IRR = 1.05, 95% CI: 1.00 to 1.10, per 10 cm). Ectopic fat but not general adiposity measures were associated with prevalent CVD in men with HIV. 相似文献
105.
Fraldi A Zito E Annunziata F Lombardi A Cozzolino M Monti M Spampanato C Ballabio A Pucci P Sitia R Cosma MP 《Human molecular genetics》2008,17(17):2610-2621
Sulfatase modifying factor 1 (SUMF1) encodes for the formylglicine generating enzyme, which activates sulfatases by modifying a key cysteine residue within their catalytic domains. SUMF1 is mutated in patients affected by multiple sulfatase deficiency, a rare recessive disorder in which all sulfatase activities are impaired. Despite the absence of canonical retention/retrieval signals, SUMF1 is largely retained in the endoplasmic reticulum (ER), where it exerts its enzymatic activity on nascent sulfatases. Part of SUMF1 is secreted and paracrinally taken up by distant cells. Here we show that SUMF1 interacts with protein disulfide isomerase (PDI) and ERp44, two thioredoxin family members residing in the early secretory pathway, and with ERGIC-53, a lectin that shuttles between the ER and the Golgi. Functional assays reveal that these interactions are crucial for controlling SUMF1 traffic and function. PDI couples SUMF1 retention and activation in the ER. ERGIC-53 and ERp44 act downstream, favoring SUMF1 export from and retrieval to the ER, respectively. Silencing ERGIC-53 causes proteasomal degradation of SUMF1, while down-regulating ERp44 promotes its secretion. When over-expressed, each of three interactors favors intracellular accumulation. Our results reveal a multistep control of SUMF1 trafficking, with sequential interactions dynamically determining ER localization, activity and secretion. 相似文献
106.
Andrew?Feola Pamela?Moalli Marianna?Alperin Robbie?Duerr Robin?E.?Gandley Steven?AbramowitchEmail author 《Annals of biomedical engineering》2011,39(1):549-558
Remodeling of vaginal extracellular matrix and smooth muscle likely plays a critical role in reducing the risk of maternal
injury during vaginal delivery by altering the mechanical properties to increase distension and reduce stress. Long-Evans
rats were divided into five groups to examine the passive mechanical and active contractile properties throughout pregnancy
and postpartum: virgin (n = 17), mid-pregnant (Day 14–16, n = 12), late-pregnant (Day 20–22, n = 14), immediate postpartum (0–2 h after delivery, n = 14), and 4 week postpartum (n = 15). Longitudinal sections of vaginal tissue were loaded to failure uniaxially for passive mechanical or active contractile
properties were examined. For passive mechanics, the tangent modulus decreased 45% by mid-pregnancy and immediately postpartum
(p < 0.001). The ultimate strain continuously increased up to 43% higher than virgin animals (p = 0.007) in the immediate postpartum group. For active mechanics, the maximal contractile force was 36–56% lower through
immediate postpartum animals, and was significantly more sensitive to K+ throughout pregnancy and postpartum (p = 0.003). The changes observed in the passive and active properties of the rat vagina are consistent with what would be expected
from a tissue that is remodeling to maximize its ability to distend at the time of vaginal delivery to facilitate passage
of the fetus with minimal injury. 相似文献
107.
Biological integration of an implant to surrounding bone is an important event for its clinical success and is driven by numerous factors, including the attraction of bone forming cells. The implant's surface properties influence the initial cell response at the cell/material interface, ultimately affecting the rate and quality of new tissue formation and the stability of the implant. As a consequence, various surface treatments have been developed to increase the clinical performance of titanium-based implants. Among them, the Anodic Plasma-Chemical (APC) technique allows for the combined chemical and morphological modification of titanium surfaces in a single process step. In the present study, we compared the potential of APC surface treatment of high-strength titanium alloys with vacuum plasma spray treatment and yellow gold anodization in supporting osteogenic differentiation of two different osteoprogenitor cell types. Both human fetal osteoblast cell line (hFOB1.19) and human mesenchymal stromal cells showed extensive cell spreading, faster cell growth and differentiation on APC surfaces compared to vacuum plasma spray treated and yellow gold anodized surfaces. Our findings showed that APC titanium-based surfaces provided an effective substrate for osteoprogenitor cells adhesion, proliferation and differentiation. 相似文献
108.
Yu H Tawab-Amiri A Dzutsev A Sabatino M Aleman K Yarchoan R Terabe M Sui Y Berzofsky JA 《Journal of leukocyte biology》2011,90(1):205-214
CD4(+) Th cells are important for the induction and maintenance of antigen-specific CD8(+) T cell function, so their loss or dysfunction in HIV-infected or cancer patients could reduce the patients' ability to control viral infection. Previous work in murine systems indicated that IL-15 codelivered with vaccines could overcome CD4(+) Th cell deficiency for induction of functionally efficient CD8(+) T cells and maintenance of viral-specific CTLs, but its efficacy in helping primary human CD8(+) T cell responses is unknown. In the present study, a peptide-pulsed, DC-based human coculture ex vivo system was used to study the role of IL-15 in overcoming CD4(+) Th deficiency to elicit CD8(+) T cell responses in CD4-depleted PBMCs from healthy individuals and PBMCs from HIV-1-infected patients. We found that IL-15 could overcome CD4(+) Th deficiency to induce primary and recall memory CD8(+) T cell responses in healthy individuals. Moreover, in CD4-deficient, HIV-1-infected patients with diminished CD8(+) T cell responses, IL-15 greatly enhanced CD8(+) T cell responses to alloantigen. These results suggest that IL-15 may be useful in the development of therapeutic and preventive vaccines against cancers and viral infections in patients defective in CD4(+) Th cell. 相似文献
109.
Grigorijs Plakhins Arvids Irmejs Andris Gardovskis Signe Subatniece Santa Rozite Marianna Bitina Guntars Keire Gunta Purkalne Uldis Teibe Genadijs Trofimovics Edvins Miklasevics Janis Gardovskis 《BMC medical genetics》2011,12(1):147
Background
Mutations in the high penetrance breast and ovarian cancer susceptibility gene BRCA1 account for a significant percentage of hereditary breast and ovarian cancer cases. Genotype-phenotype correlations of BRCA1 mutations located in different parts of the BRCA1 gene have been described previously; however, phenotypic differences of specific BRCA1 mutations have not yet been fully investigated. In our study, based on the analysis of a population-based series of unselected breast and ovarian cancer cases in Latvia, we show some aspects of the genotype-phenotype correlation among the BRCA1 c.4034delA (4153delA) and c.5266dupC (5382insC) founder mutation carriers.Methods
We investigated the prevalence of the BRCA1 founder mutations c.4034delA and c.5266dupC in a population-based series of unselected breast (n = 2546) and ovarian (n = 795) cancer cases. Among the BRCA1 mutation carriers identified in this analysis we compared the overall survival, age at diagnosis and family histories of breast and ovarian cancers.Results
We have found that the prevalence of breast and ovarian cancer cases (breast: ovarian cancer ratio) differs significantly among the carriers of the c.5266dupC and c.4034delA founder mutations (OR = 2.98, 95%CI = 1.58 to 5.62, P < 0.001). We have also found a difference in the prevalence of breast and ovarian cancer cases among the 1st and 2nd degree relatives of the c.4034delA and c.5266dupC mutation carriers. In addition, among the breast cancer cases the c.4034delA mutation has been associated with a later age of onset and worse clinical outcomes in comparison with the c.5266dupC mutation.Conclusions
Our data suggest that the carriers of the c.4034delA and c.5266dupC founder mutations have different risks of breast and ovarian cancer development, different age of onset and prognosis of breast cancer.110.
Marianna Virtanen Jane E. Ferrie David Gimeno Jussi Vahtera Marko Elovainio Archana Singh-Manoux Michael G. Marmot Mika Kivim?ki 《Sleep》2009,32(6):737-745