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31.
Timely triggering of homeostatic mechanisms involved in the regulation of T-cell levels in SIVsm-infected sooty mangabeys 下载免费PDF全文
Muthukumar A Zhou D Paiardini M Barry AP Cole KS McClure HM Staprans SI Silvestri G Sodora DL 《Blood》2005,106(12):3839-3845
Sooty mangabeys, the natural host of simian immunodeficiency virus (SIVsm), generally avoid progressive depletion of CD4+ T cells and opportunistic infections associated with infection of humans (HIV) and macaques (SIVmac). The means by which the SIVsm-infected mangabeys maintain CD4+ T-cell levels despite high rates of viral replication is unknown. One cytokine that has a key role in the regulation of T-cell levels is interleukin-7 (IL-7). Here, the longitudinal assessment of 6 SIVsm-infected mangabeys identified an early increase in plasma IL-7 levels at weeks 1 to 5 after infection. This IL-7 increase correlated with an early decline in CD4+ T-cell levels (decline of 492-1171 cells/microL) accompanying acute viremia. Elevated IL-7 levels were followed by increased T-cell proliferation (Ki67) and maintenance of lower but stable (more than 500 cells/microL) CD4+ T-cell levels in each mangabey through 37 weeks of infection. These data contrast with our earlier studies in SIVmac-infected macaques, in which the IL-7 increase was delayed until 20 to 40 weeks after infection, just before the onset of simian AIDS. Taken together, these data suggest that timely triggering of IL-7 is important for stabilizing healthy T-cell levels in mangabeys and that timely administration of exogenous IL-7 may show benefit during pathogenic SIVmac and HIV infection. 相似文献
32.
Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures 总被引:6,自引:9,他引:6
Lokhorst HM; Lamme T; de Smet M; Klein S; de Weger RA; van Oers R; Bloem AC 《Blood》1994,84(7):2269-2277
Long-term bone marrow cultures (LTBMC) from patients with multiple myeloma (MM) and normal donors were analyzed for immunophenotype and cytokine production. Both LTBMC adherent cells from myeloma and normal donor origin expressed CD10, CD13, the adhesion molecules CD44, CD54, vascular cell adhesion molecule 1, very late antigen 2 (VLA-2), and VLA- 5, and were positive for extracellular matrix components fibronectin, laminin, and collagen types 3 and 4. LTBMC from myeloma patients and normal donors spontaneously secreted interleukin-6 (IL-6). However, levels of IL-6 correlated with the stage of disease; highest levels of IL-6 were found in LTBMC from patients with active myeloma. To identify the origin of IL-6 production, LTBMC from MM patients and normal donors were cocultured with BM-derived myeloma cells and cells from myeloma cell lines. IL-6 was induced by plasma cell lines that adhered to LTBMC such as ARH-77 and RPMI-8226, but not by nonadhering cell lines U266 and FRAVEL. Myeloma cells strongly stimulated IL-6 secretion in cocultures with LTBMC adherent cells from normal donors and myeloma patients. When direct cellular contact between LTBMC and plasma cells was prevented by tissue-culture inserts, no IL-6 production was induced. This implies that intimate cell-cell contact is a prerequisite for IL-6 induction. Binding of purified myeloma cells to LTBMC adherent cells was partly inhibited by monoclonal antibodies against adhesion molecules VLA-4, CD44, and lymphocyte function-associated antigen 1 (LFA-1) present on the plasma cell. Antibodies against VLA-4, CD29, and LFA-1 also inhibited the induced IL-6 secretion in plasma cell-LTBMC cocultures. In situ hybridization studies performed before and after coculture with plasma cells indicated that LTBMC adherent cells produce the IL-6. These results suggest that the high levels of IL-6 found in LTBMC of MM patients with active disease are a reflection of their previous contact with tumor cells in vivo. These results provide a new perspective on tumor growth in MM and emphasize the importance of plasma cell-LTBMC interaction in the pathophysiology of MM. 相似文献
33.
Bhalachandra?S?KodkanyEmail author Richard?J?Derman Narayan?V?Honnungar Naresh?K?Tyagi Shivaprasad?S?Goudar Shivanand?C?Mastiholi Janet?L?Moore Elizabeth?M?McClure Nancy?Sloan Robert?L?Goldenberg 《Reproductive health》2015,12(Z2):S3
Background
Pregnancy-related vital registration is important to inform policy to reduce maternal, fetal and newborn mortality, yet few systems for capturing accurate data are available in low-middle income countries where the majority of the mortality occurs. Furthermore, methods to effectively implement high-quality registration systems have not been described. The goal of creating the registry described in this paper was to inform public health policy makers about pregnancy outcomes in our district so that appropriate interventions to improve these outcomes could be undertaken and to position the district to be a leader in pregnancy-related public health research.Methods
We created a prospective maternal and newborn health registry in Belgaum, Karnataka State, India. To initiate this registry, we worked with the Ministry of Health to first establish estimated birth rates and define the catchment areas of the clusters, working within the existing health system and primary health centers. We also undertook household surveys to identify women likely to become pregnant. We then implemented monitoring measures to ensure high quality and completeness of the maternal newborn health registry. All pregnant women in the catchment area were identified, consented and enrolled during pregnancy, with follow-up visits to ascertain pregnancy outcomes and mother/infant status at 42-days postpartum.Results
From 2008 through 2014, we demonstrated continued improvements in both the coverage for enrollment and accuracy of reporting pregnancy outcomes within the defined catchment area in Belgaum, India. Nearly 100% of women enrolled had follow-up at birth and 99% had 42-day follow-up. Furthermore, we facilitated earlier enrollment of women during pregnancy while achieving more timely follow-up and decreased time of reporting from the date of the pregnancy event.Conclusions
We created a pregnancy-related registry which includes demographic data, risk factors, and outcomes allowing for high rates of ascertainment and follow-up while working within the existing health system. Understanding the elements of the system used to create the registry is important to improve the quality of the results. Tracking of pregnancies and their outcomes is an important step toward reducing maternal and perinatal mortality.34.
35.
Rod McClure Scott Kegler Tamzyn Davey Fiona Clay 《American journal of public health》2015,105(12):e37-e43
Background. The definition of injury that underpins the contemporary approach to injury prevention is an etiological definition relating to bodily damage arising from transfer of energy to tissues of the body beyond the limits compatible with physiological function. Causal factors proximal to the energy transfer are nested within a more complex set of contextual determinants. For effective injury control, understanding of these determinants is critical.Objectives. The primary aims of this study were to describe the area-level determinants that have been included in multilevel analyses of childhood injury and to quantify the relationships between these area-level exposures and injury outcomes.Search methods. We conducted a systematic review of peer-reviewed, English-language literature published in scientific journals between January 1997 and July 2014, reporting studies that employed multilevel analyses to quantify the eco-epidemiological causation of physical unintentional injuries to children aged 16 years and younger. We conducted and reported the review in accordance with the PRISMA guidelines.Selection criteria. We included etiological studies of causal risk factors for unintentional traumatic injuries to children aged 0 to 16 years. Methodological inclusion criteria were as follows:
- Epidemiological studies quantifying the relationship between risk factors (at various levels) and injury occurrence in the individual;
- Studies that recognized individual exposure and at least 1 higher level of exposure with units at lower levels or microunits (e.g., individuals) nested within units at higher levels or macrounits (e.g., areas or neighborhoods);
- Injury outcomes (dependent variable) examined at the individual level; and
- Central analytic techniques belonging to the following categories: multilevel models, hierarchical models, random effects models, random coefficient models, covariance components models, variance components models, and mixed models.
36.
David R. Buys Virginia J. Howard Leslie A. McClure Katie Crawford Buys Patricia Sawyer Richard M. Allman Emily B. Levitan 《American journal of public health》2015,105(6):1181-1188
Objectives. We evaluated the effect of neighborhood disadvantage (ND) on older adults’ prevalence, awareness, treatment, and control of hypertension.Methods. Data were from the University of Alabama at Birmingham Study of Aging, an observational study of 1000 community-dwelling Black and White Alabamians aged 65 years and older, in 1999 to 2001. We assessed hypertension prevalence, awareness, treatment, and control with blood pressure measurements and self-report data. We assessed ND with US Census data corresponding with participants’ census tracts, created tertiles of ND, and fit models with generalized estimating equations via a logit link function with a binomial distribution. Adjusted models included variables assessing personal advantage and disadvantage, place-based factors, sociodemographics, comorbidities, and health behaviors.Results. Living in mid-ND (adjusted odds ratio [AOR] = 1.6; 95% confidence interval [CI] = 1.2, 2.1) and high-ND tertiles (AOR = 1.8; 95% CI = 1.3, 2.3) was associated with higher hypertension prevalence, and living in high-ND tertiles was associated with lower odds of controlled hypertension (AOR = 0.6; 95% CI = 0.4, 0.6). In adjusted models, ND was not associated with hypertension awareness or treatment.Conclusions. These findings show that neighborhood environmental factors matter for hypertension outcomes and suggest the importance of ND for hypertension management in older adults.The characteristics of the geographic spaces or neighborhoods where people live influence their health throughout the life course.1–9 The mechanisms whereby neighborhood characteristics affect individuals’ health include psychosocial and material resources in those geographic spaces. Specifically, neighborhoods have the potential to be a source of social capital, providing support to persons in need; to have physical capital, offering parks and recreation resources for physical activity; and to have human capital, generating economic output. Any of these resources can contribute to the overall well-being of individuals living there.10 Alternatively, stress caused by high crime, low social support, limited economic resources, or a lack of material resources such as health services6 may ultimately negatively affect the health of individuals living in a neighborhood. Furthermore, limited community-based assistance programs, as well as limited access to healthful foods or adequate shopping opportunities and recreational facilities11 in disadvantaged neighborhoods may also have adverse effects on health. The daily stress of living in such disadvantaged neighborhoods may place a high burden on individuals’ physiological systems, a burden which is sometimes called allostatic load.12,13These risks and benefits of neighborhood contexts may accrue over a long period of time and may affect people either right away or for many years in the future14 and lead to conditions such as hypertension. In fact, neighborhood-level psychosocial and material deprivations are particularly problematic for individuals’ cardiovascular health and for management of cardiovascular risk factors. In 2004, Diez Roux et al.15 demonstrated an association between negative environments and both cardiovascular and noncardiovascular mortality. Other researchers have found similar effects, including Mujahid et al.16 who showed that walkability, access to healthy food, greater safety, and greater social cohesion were associated with a lower likelihood of hypertension.Although these findings are useful for gaining insights into the general population, work is needed to assess the effects of neighborhood characteristics on specific, unique subpopulations. To that end, there has been a growing interest in the effects of neighborhood context on older adults because of their potentially greater sensitivity (than the general population) to the effects of their neighborhood contexts on health.8,17–22 This is particularly important, as Lawton and Simon purported in the environmental docility hypothesis,23 because, as persons age and become more ill, losing control of their ability to perform activities of daily living, they may become more sensitive to characteristics of their environments, including the neighborhoods where they live. Specifically, then, older adults’ inability to navigate through disadvantaged neighborhoods may put them at higher risk for hypertension because of more concentrated exposure to psychosocial stressors. In addition, deprivation of health services including access to physicians and pharmacies in disadvantaged neighborhoods may cause adverse outcomes. Finally, older adults’ negative perception of their neighborhood environment may have a negative impact on their likelihood of being mobile and active, even when, in reality, theirs is not an unsafe or disadvantaged neighborhood.Although there is a burgeoning literature on the relationship between neighborhood characteristics and cardiovascular outcomes and a growing interest in neighborhood effects on older adults, no work known to these authors has examined neighborhood effects on hypertension specifically among older adults. Therefore, we aimed to assess if an association exists between neighborhood disadvantage (ND), measured by a validated ND index (NDI),24 and hypertension prevalence, awareness, treatment, and control in a cohort of community-dwelling older adults. 相似文献
37.
38.
39.
Adams GB Pym AS Poznansky MC McClure MO Weber JN 《AIDS research and human retroviruses》1999,15(6):551-559
This study investigated the effects of a combination antiretroviral drug regimen (indinavir and two nucleoside analogs or ritonavir and saquinavir) on the levels of CD34+ colony-forming units (CFU-Cs) in the peripheral blood of HIV-1+ patients. Ten patients who were receiving combination antiretroviral drug therapy were studied and their peripheral blood CD34+ CFU-Cs were measured prior to, 1 month after, and 4 to 6 months after the commencement of therapy. The levels of CD4+ T cells increased significantly in these patients (paired t test, p = 0.0027) and plasma viral load became undetectable in all but one patient studied. Measurements of the CFU-Cs showed that their levels tended to increase on the commencement of therapy, and these levels became significantly higher than baseline by 4-6 months (paired t test, p = 0.0293). Analysis of the different colony phenotype demonstrated that the main contributor to this increase consisted of burst-forming unit erythroid (BFU-E) cells. These data also demonstrated that there was an inverse correlation between the rise in CFU-Cs at 4-6 months compared with CD4+ cell, CD8+ cell, and neutrophil counts, and hemoglobin concentration, at baseline. The demonstrated increase in the levels of CD34+ CFU-Cs suggests that HIV-1 may have an inhibitory effect on these cells in vivo, and that this inhibition may be abrogated by suppression of viral replication. 相似文献
40.
W E Collins H M McClure E Strobert V Filipski J C Skinner P S Stanfill B B Richardson C Morris 《The American journal of tropical medicine and hygiene》1990,42(2):99-103
Nine splenectomized chimpanzees were infected with the Uganda I/CDC strain of Plasmodium malariae. Two had no history of previous malarial infection, whereas 6 had been infected with P. vivax and 1 with P. vivax and P. ovale. The animals with no previous infection had maximum parasitemias of 8,740 and 10,800/mm3. The other animals had maximum parasite counts of 930-75,700/mm3. Anopheles freeborni, An. stephensi, An. dirus, An. maculatus, An. quadrimaculatus, An. culicifacies, An. arabiensis, and An. gambiae were readily infected by feeding through membranes on heparinized blood from these animals. 相似文献