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71.
John R. Koethe Andrew O. Westfall Dora K. Luhanga Gina M. Clark Jason D. Goldman Priscilla L. Mulenga Ronald A. Cantrell Benjamin H. Chi Isaac Zulu Michael S. Saag Jeffrey S. A. Stringer 《PloS one》2010,5(3)
Background
The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree).Methodology
Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months.Principal Findings
From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites.Conclusions
A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings.Trial Registration
Clinicaltrials.gov NCT00929604相似文献72.
Anika I Tsuchida Michiel Beekhuizen Marieke C ‘t Hart Timothy RDJ Radstake Wouter JA Dhert Daniel BF Saris Gerjo JVM van Osch Laura B Creemers 《Arthritis research & therapy》2014,16(5)
Introduction
This study aimed to evaluate whether profiles of several soluble mediators in synovial fluid and cartilage tissue are pathology-dependent and how their production is related to in vitro tissue formation by chondrocytes from diseased and healthy tissue.Methods
Samples were obtained from donors without joint pathology (n = 39), with focal defects (n = 65) and osteoarthritis (n = 61). A multiplex bead assay (Luminex) was performed measuring up to 21 cytokines: Interleukin (IL)-1α, IL-1β, IL-1RA, IL-4, IL-6, IL-6Rα, IL-7, IL-8, IL-10, IL-13, tumor necrosis factor (TNF)α, Interferon (IFN)γ, oncostatin M (OSM), leukemia inhibitory factor (LIF), adiponectin, leptin, monocyte chemotactic factor (MCP)1, RANTES, basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), vascular growth factor (VEGF).Results
In synovial fluid of patients with cartilage pathology, IL-6, IL-13, IFNγ and OSM levels were higher than in donors without joint pathology (P ≤0.001). IL-13, IFNγ and OSM were also different between donors with cartilage defects and OA (P <0.05). In cartilage tissue from debrided defects, VEGF was higher than in non-pathological or osteoarthritic joints (P ≤0.001). IL-1α, IL-6, TNFα and OSM concentrations (in ng/ml) were markedly higher in cartilage tissue than in synovial fluid (P <0.01). Culture of chondrocytes generally led to a massive induction of most cytokines (P <0.001). Although the release of inflammatory cytokines was also here dependent on the pathological condition (P <0.001) the actual profiles were different from tissue or synovial fluid and between non-expanded and expanded chondrocytes. Cartilage formation was lower by healthy unexpanded chondrocytes than by osteoarthritic or defect chondrocytes.Conclusions
Several pro-inflammatory, pro-angiogenic and pro-repair cytokines were elevated in joints with symptomatic cartilage defects and/or osteoarthritis, although different cytokines were elevated in synovial fluid compared to tissue or cells. Hence a clear molecular profile was evident dependent on disease status of the joint, which however changed in composition depending on the biological sample analysed. These alterations did not affect in vitro tissue formation with these chondrocytes, as this was at least as effective or even better compared to healthy chondrocytes. 相似文献73.
74.
Namthip Witayavanitkul Younss Ait Mou Diederik W. D. Kuster Ramzi J. Khairallah Jason Sarkey Suresh Govindan Xin Chen Ying Ge Sudarsan Rajan David F. Wieczorek Thomas Irving Margaret V. Westfall Pieter P. de Tombe Sakthivel Sadayappan 《The Journal of biological chemistry》2014,289(13):8818-8827
Myocardial infarction (MI) is associated with depressed cardiac contractile function and progression to heart failure. Cardiac myosin-binding protein C, a cardiac-specific myofilament protein, is proteolyzed post-MI in humans, which results in an N-terminal fragment, C0-C1f. The presence of C0-C1f in cultured cardiomyocytes results in decreased Ca2+ transients and cell shortening, abnormalities sufficient for the induction of heart failure in a mouse model. However, the underlying mechanisms remain unclear. Here, we investigate the association between C0-C1f and altered contractility in human cardiac myofilaments in vitro. To accomplish this, we generated recombinant human C0-C1f (hC0C1f) and incorporated it into permeabilized human left ventricular myocardium. Mechanical properties were studied at short (2 μm) and long (2.3 μm) sarcomere length (SL). Our data demonstrate that the presence of hC0C1f in the sarcomere had the greatest effect at short, but not long, SL, decreasing maximal force and myofilament Ca2+ sensitivity. Moreover, hC0C1f led to increased cooperative activation, cross-bridge cycling kinetics, and tension cost, with greater effects at short SL. We further established that the effects of hC0C1f occur through direct interaction with actin and α-tropomyosin. Our data demonstrate that the presence of hC0C1f in the sarcomere is sufficient to induce depressed myofilament function and Ca2+ sensitivity in otherwise healthy human donor myocardium. Decreased cardiac function post-MI may result, in part, from the ability of hC0C1f to bind actin and α-tropomyosin, suggesting that cleaved C0-C1f could act as a poison polypeptide and disrupt the interaction of native cardiac myosin-binding protein C with the thin filament. 相似文献
75.
The signal produced by fluorescence in situ hybridization (FISH) often is inconsistent among cells and sensitivity is low. Small DNA targets on the chromatin are difficult to detect. We report here an improved nick translation procedure for Texas red and Alexa Fluor 488 direct labeling of FISH probes. Brighter probes can be obtained by adding excess DNA polymerase I. Using such probes, a 30 kb yeast transgene, and the rp1, rp3 and zein multigene clusters were clearly detected. 相似文献
76.
77.
Light and electron microscopic localization of a monoclonal antibody in neurons in situ in the head region of Hydra 总被引:1,自引:0,他引:1
A mouse monoclonal antibody to Hydra attenuata was used to demonstrate immunoreactive product in neurons in situ, in both whole mount and sectioned hypostomes and tentacles of H. oligactis and H. littoralis. Immunoreactive cells were concentrated around the mouth and scattered along the length of the tentacles. In the hypostome, nerve cells sent one or more processes orally and the others aborally but the processes were more distinctly stained in H. oligactis. A thin strand of five to six perihypostomal neurons was present close to the hypostome-tentacle junction. In the tentacles, neurons with long processes contacted up to five different batteries of nematocysts. Neural processes were associated with nematocyst batteries in three ways: 1) forming a perikaryal loop to encircle a centrally located stenotele, 2) branching at a distance from the perikaryon to contact a variety of nematocysts, and 3) terminal branching by one or more neurons with contacts on one to several nematocysts within a battery. Immunocytochemical localization of neurons in Hydra by light microscopy was correlated for the first time with electron microscopy. Peroxidase-antiperoxidase (PAP)-positive sensory cells were concentrated around the mouth opening. PAP-positive ganglion cells were predominant in the tentacles. Sensory cells were elongate or spindle-shaped (unipolar), triangular with two oppositely directed processes (bipolar), and multipolar (tripolar or tetrapolar) with one of the processes extending to the epidermal surface. Ganglion cells were either unipolar or bipolar or multipolar, with neurites paralleling the mesoglea and occasionally having processes abut on it. 相似文献
78.
Shell morphology and color of the subtidal whelk Buccinum undatum exhibit fine‐scaled spatial patterns
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Hildur Magnúsdóttir Snæbjörn Pálsson Kristen M. Westfall Zophonías O. Jónsson Erla Björk Örnólfsdóttir 《Ecology and evolution》2018,8(9):4552-4563
Geographical patterns in morphology can be the result of divergence among populations due to neutral or selective changes and/or phenotypic plasticity in response to different environments. Marine gastropods are ideal subjects on which to explore these patterns, by virtue of the remarkable intraspecific variation in life‐history traits and morphology often observed across relatively small spatial scales. The ubiquitous N‐Atlantic common whelk (Buccinum undatum) is well known for spatial variation in life‐history traits and morphology. Previous studies on genetic population structure have revealed that it exhibits significant differentiation across geographic distances. Within Breiðafjörður Bay, a large and shallow bay in W‐Iceland, genetic differentiation was demonstrated between whelks from sites separated by just 20 km. Here, we extended our previous studies on the common whelk in Breiðafjörður Bay by quantifying phenotypic variation in shell morphology and color throughout the Bay. We sought to test whether trait differentiation is dependent on geographic distance and/or environmental variability. Whelk in Breiðafjörður Bay displayed fine‐scale patterns of spatial variation in shape, thickness, and color diversity. Differentiation increased with increasing distance between populations, indicating that population connectivity is limited. Both shape and color varied along a gradient from the inner part of the bay in the east to the outer part in the west. Whelk shells in the innermost part of Breiðafjörður Bay were thick with an elongate shell, round aperture, and low color diversity, whereas in the outer part of the bay the shells were thinner, rounder, with a more elongate aperture and richer color diversity. Significant site‐specific difference in shell traits of the common whelk in correlation with environmental variables indicates the presence of local ecotypes and limited demographic connectivity. 相似文献
79.
A program package is described in which vegetation data can be objectively classified and analysed. Classification is based on minimum entropy. Results show that in a comparison with TWINSPAN, improvements to the relevé sequence, in terms of community variation, can be obtained. Furthermore, TWINSPAN classifications are shown to be dependent on a particular relevé input sequence. 相似文献
80.