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Search Results: 1 - 10 of 181174 matches for " William E. Collins "
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Establishment of an In Vitro Assay for Assessing the Effects of Drugs on the Liver Stages of Plasmodium vivax Malaria
Rana Chattopadhyay,Soundarapandian Velmurugan,Chinnamma Chakiath,Lucy Andrews Donkor,Wilbur Milhous,John W. Barnwell,William E. Collins,Stephen L. Hoffman
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0014275
Abstract: Plasmodium vivax (Pv) is the second most important human malaria parasite. Recent data indicate that the impact of Pv malaria on the health and economies of the developing world has been dramatically underestimated. Pv has a unique feature in its life cycle. Uninucleate sporozoites (spz), after invasion of human hepatocytes, either proceed to develop into tens of thousands of merozoites within the infected hepatocytes or remain as dormant forms called hypnozoites, which cause relapses of malaria months to several years after the primary infection. Elimination of malaria caused by Pv will be facilitated by developing a safe, highly effective drug that eliminates Pv liver stages, including hypnozoites. Identification and development of such a drug would be facilitated by the development of a medium to high throughput assay for screening drugs against Pv liver stages. We undertook the present pilot study to (1) assess the feasibility of producing large quantities of purified, vialed, cryopreserved Pv sporozoites and (2) establish a system for culturing the liver stages of Pv in order to assess the effects of drugs on the liver stages of Pv. We used primaquine (PQ) to establish this assay model, because PQ is the only licensed drug known to clear all Pv hepatocyte stages, including hypnozoites, and the effect of PQ on Pv hepatocyte stage development in vitro has not previously been reported. We report that we have established the capacity to reproducibly infect hepatoma cells with purified, cyropreserved Pv spz from the same lot, quantitate the primary outcome variable of infected hepatoma cells and demonstrate the inhibitory activity of primaquine on the infected hepatoma cells. We have also identified small parasite forms that may be hypnozoites. These data provide the foundation for finalizing a medium throughput, high content assay to identify new drugs for the elimination of all Pv liver stages.
B lymphocyte stimulator (BLyS) isoforms in systemic lupus erythematosus: disease activity correlates better with blood leukocyte BLyS mRNA levels than with plasma BLyS protein levels
Christopher E Collins, Amanda L Gavin, Thi-Sau Migone, David M Hilbert, David Nemazee, William Stohl
Arthritis Research & Therapy , 2005, DOI: 10.1186/ar1855
Abstract: B lymphocyte stimulator (BLyS; a trademark of Human Genome Sciences, Inc., Rockville, MD, USA) is a 285-amino-acid member of the tumor necrosis factor ligand superfamily [1-3]. A causal relation between constitutive overproduction of BLyS and development of systemic lupus erythematosus (SLE)-like illness has incontrovertibly been established in mice. BLyS-transgenic mice often develop SLE-like features as they age [3-5], and SLE-prone (NZB × NZW)F1 (BWF1) and MRL-lpr/lpr mice respond clinically to treatment with BLyS antagonists (decreased disease progression and improved survival) [3,6].Considerable inferential evidence points to a role for BLyS overproduction in human SLE as well. Cross-sectional studies have demonstrated elevated circulating levels of BLyS in 20–30% of human SLE patients tested at a single point in time [7,8]. Moreover, a 12-month longitudinal study documented persistently elevated serum BLyS levels in about 25% of SLE patients and intermittently elevated serum BLyS levels in an additional 25% of patients [9]. Remarkably, circulating BLyS levels did not correlate with disease activity (measured using the SLE Disease Activity Index [SLEDAI]) in these cross-sectional or longitudinal studies [7-9]. Although a statistically significant correlation between circulating BLyS levels and SLEDAI has been appreciated in a more recent 24-month longitudinal study of 245 SLE patients (with >1,700 plasma samples analyzed) [10], the correlation remains weak.The limited correlation between circulating BLyS protein levels and disease activity in these studies may have exposed an inadequacy of the former to reflect faithfully endogenous BLyS overproduction. In addition to the rate of BLyS protein production, several other factors (for example, utilization and excretion) can affect circulating BLyS protein levels. Although there are no practicable means of directly measuring in vivo BLyS production per se in humans, the level of BLyS mRNA may serve as a better surro
Protective Efficacy of a Plasmodium vivax Circumsporozoite Protein-Based Vaccine in Aotus nancymaae Is Associated with Antibodies to the Repeat Region
Anjali Yadava ,Cysha E. Hall,JoAnn S. Sullivan,Douglas Nace,Tyrone Williams,William E. Collins,Christian F. Ockenhouse,John W. Barnwell
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0003268
Abstract: We have previously reported that Vivax Malaria Protein 001 (VMP001), a vaccine candidate based on the circumsporozoite protein of Plasmodium vivax, is immunogenic in mice and rhesus monkeys in the presence of various adjuvants. In the present study, we evaluated the immunogenicity and efficacy of VMP001 formulated with a TLR9 agonist in a water-in-oil emulsion. Following immunization, the vaccine efficacy was assessed by challenging Aotus nancymaae monkeys with P. vivax sporozoites. Monkeys from both the low- and high-dose vaccine groups generated strong humoral immune responses to the vaccine (peak median titers of 291,622), and its subunits (peak median titers to the N-term, central repeat and C-term regions of 22,188; 66,120 and 179,947, respectively). 66.7% of vaccinated monkeys demonstrated sterile protection following challenge. Protection was associated with antibodies directed against the central repeat region. The protected monkeys had a median anti-repeat titer of 97,841 compared to 14,822 in the non-protected monkeys. This is the first report demonstrating P. vivax CSP vaccine-induced protection of Aotus monkeys challenged with P. vivax sporozoites.
Heterochromatic Threads Connect Oscillating Chromosomes during Prometaphase I in Drosophila Oocytes
Stacie E. Hughes equal contributor,William D. Gilliland equal contributor,Jeffrey L. Cotitta,Satomi Takeo,Kim A. Collins,R. Scott Hawley
PLOS Genetics , 2009, DOI: 10.1371/journal.pgen.1000348
Abstract: In Drosophila oocytes achiasmate homologs are faithfully segregated to opposite poles at meiosis I via a process referred to as achiasmate homologous segregation. We observed that achiasmate homologs display dynamic movements on the meiotic spindle during mid-prometaphase. An analysis of living prometaphase oocytes revealed both the rejoining of achiasmate X chromosomes initially located on opposite half-spindles and the separation toward opposite poles of two X chromosomes that were initially located on the same half spindle. When the two achiasmate X chromosomes were positioned on opposite halves of the spindle their kinetochores appeared to display proper co-orientation. However, when both Xs were located on the same half spindle their kinetochores appeared to be oriented in the same direction. Thus, the prometaphase movement of achiasmate chromosomes is a congression-like process in which the two homologs undergo both separation and rejoining events that result in the either loss or establishment of proper kinetochore co-orientation. During this period of dynamic chromosome movement, the achiasmate homologs were connected by heterochromatic threads that can span large distances relative to the length of the developing spindle. Additionally, the passenger complex proteins Incenp and Aurora B appeared to localize to these heterochromatic threads. We propose that these threads assist in the rejoining of homologs and the congression of the migrating achiasmate homologs back to the main chromosomal mass prior to metaphase arrest.
Comparison of flow characteristics and vascular reactivity of radial artery and long saphenous vein grafts [NCT00139399]
William CF Chong, Peter Collins, Carolyn M Webb, Anthony C De Souza, John R Pepper, Christopher S Hayward, Neil E Moat
Journal of Cardiothoracic Surgery , 2006, DOI: 10.1186/1749-8090-1-4
Abstract: Angiograms from 52 males taken 3.7 ± 1.0 months after CABG surgery were analyzed using adjusted Thrombolysis in Myocardial Infarction (TIMI) frame count. Graft and target coronary artery dimensions were measured using quantitative coronary angiography. Estimated TIMI velocity (VE) and volume flow (FE) were then calculated. A further 7 patients underwent in-vivo graft flow responses assessments to adenosine, acetylcholine and isosorbide dinitrate (ISDN) using intravascular Doppler.The VE for RA grafts was significantly greater than LSV grafts (P = 0.002), however there was no difference in volume FE (P = 0.20). RA grafts showed positive endothelium-dependent and -independent vasodilatation, and LSV grafts showed no statistically significant response to adenosine and acetylcholine. There was no difference in flow velocity or volume responses. Seven RA grafts (11%) had compromised patency (4 (6%) ≥ 50% stenosis in the proximal/distal anastomoses, and 3 (5%) diffuse narrowing). Thirty-seven (95%) LSV grafts achieved perfect patency and 2 (5%) were occluded.The flow characteristics and flow responses of the RA graft suggest that it is a more physiological conduit than the LSV graft. The clinical relevance of the balance between imperfect patency versus the more physiological vascular function in the RA graft may be revealed by the 5-year angiographic follow-up of this trial.We compared 3-month post-operative flow characteristics and in-vivo flow responses of radial artery (RA) and long saphenous vein (LSV) grafts. Basal velocity was significantly greater in RA versus LSV grafts, but volume flow was similar. RA grafts, but not LSV grafts, showed endothelium-dependent vasodilatation.Interest in the radial artery (RA) as a coronary artery bypass graft has grown over recent years, driven by a desire to replace vein grafts with arterial grafts. Numerous observational series have shown favourable early and longer-term patency results, summarized in a recent review [1]. Further
Malaria chemoprophylaxis and the serologic response to measles and diphtheria-tetanus-whole-cell pertussis vaccines
Jennifer B Rosen, Joel G Breman, Charles R Manclark, Bruce D Meade, William E Collins, Hans O Lobel, Pierre Saliou, Jacquelin M Roberts, Pierre Campaoré, Mark A Miller
Malaria Journal , 2005, DOI: 10.1186/1475-2875-4-53
Abstract: In 1975, six villages divided into two groups of children ≤74 months of age from Burkina Faso, were assigned to receive amodiaquine hydrochloride chemoprophylaxis (CH+) every two weeks for seven months or no chemoprophylaxis (CH-). After five months, children in each group received either one dose of measles or two doses of DTP vaccines.For recipients of the measles vaccine, the seroconversion rates in CH+ and CH- children, respectively, were 93% and 96% (P > 0.05). The seroresponse rates in CH+ and CH- children respectively, were 73% and 86% for diphtheria (P > 0.05) and 77% and 91% for tetanus toxoid (P > 0.05). In a subset analysis, in which only children who strictly adhered to chemoprophylaxis criteria were included, there were, likewise, no significant differences in seroconversion or seroresponse for measles, diphtheria, or tetanus vaccines (P > 0.05). While analysis for pertussis showed a 43% (CH+) and 67% (CH-) response (P < 0.05), analyses using logistic regression to control for sex, age, chemoprophylaxis, weight-for-height Z-score, and pre-vaccination geometric mean titer (GMT), demonstrated that chemoprophylaxis was not associated with a significantly different conversion rate following DTP and measles vaccines. Seven months of chemoprophylaxis decreased significantly the malaria IFA and ELISA GMTs in the CH+ group.Malaria chemoprophylaxis prior to vaccination in malaria endemic settings did not improve or impair immunogenicity of DTP and measles vaccines. This is the first human study to look at the association between malaria chemoprophylaxis and the serologic response to whole-cell pertussis vaccine.Malaria accounts for an estimated 1 to 3 million deaths each year, with the majority occurring in children under five years of age in sub-Saharan Africa [1]. Vaccine-preventable diseases cause an estimated 1 to 2 million deaths in African children [2]. The WHO's Expanded Program on Immunization (EPI) is targeted at malarious areas, emphasizing the need to
Use of glass beads and CF 11 cellulose for removal of leukocytes from malaria-infected human blood in field settings
Goldman, Ira F.;Qari, Shoukat H.;Skinner, Jimmie;Oliveira, Salma;Nascimento, José M.;Póvoa, Marinete M.;Collins, William E.;Lal, Altaf A.;
Memórias do Instituto Oswaldo Cruz , 1992, DOI: 10.1590/S0074-02761992000400019
Abstract: passage of malaria infected blood through a two-layered column composed of acid-washed glass beads and cf 11 cellulose removes white cells from parasitized blood. however, because use of glass beads and cf 11 cellulose requires filtration of infected blood separately through these two resins and the addition of adp, the procedure is time-consuming and may be inapropriate for use in the field, especially when large numbers of blood samples are to be treated. our modification of this process yields parasitized cells free of contaminating leukocytes, and because of its operational simplicity, large numbers of blood samples can be processed. our procedure also compares well with those using expensive commercial sepacell resins in its ability to separate leukocytes from whole blood. as a test of usefulness in molecular biologic investigations, the parasites obtained from the blood of malaria-infected patients using the modified procedure yield genomic dna whose single copy gene, the circumsporozite gene, efficiently amplifies by polymerase chain reaction.
Missed Opportunities: Refusal to Confirm Reactive Rapid HIV Tests in the Emergency Department
Ishani Ganguli, Jamie E. Collins, William M. Reichmann, Elena Losina, Jeffrey N. Katz, Christian Arbelaez, Laurel A. Donnell-Fink, Rochelle P. Walensky
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0053408
Abstract: Background HIV infection remains a major US public health concern. While HIV-infected individuals now benefit from earlier diagnosis and improved treatment options, progress is tempered by large numbers of newly diagnosed patients who are lost to follow-up prior to disease confirmation and linkage to care. Methodology In the randomized, controlled USHER trial, we offered rapid HIV tests to patients presenting to a Boston, MA emergency department. Separate written informed consent was required for confirmatory testing. In a secondary analysis, we compared participants with reactive results who did and did not complete confirmatory testing to identify factors associated with refusal to complete the confirmation protocol. Principal Findings Thirteen of 62 (21.0%, 95% CI (11.7%, 33.2%)) participants with reactive rapid HIV tests refused confirmation; women, younger participants, African Americans, and those with fewer HIV risks, with lower income, and without primary care doctors were more likely to refuse. We projected that up to four true HIV cases were lost at the confirmation stage. Conclusions These findings underscore the need to better understand the factors associated with refusal to confirm reactive HIV testing and to identify interventions that will facilitate confirmatory testing and linkage to care among these populations. Trial Registration ClinicalTrials.gov NCT00502944; NCT01258582.
Performance of Nguni, Afrikander and Bonsmara cattle under drought conditions in the North West Province of Southern Africa
E. Collins-Lusweti
South African Journal of Animal Science , 2000,
Abstract: The performance of Nguni, Afrikander and Bonsmara cattle during the 1989-92 drought period in the North West Province of South Africa was compared. Results for the Nguni, Afrikander and Bonsmara respectively were as follows: birth mass - 30.3, 30.2, 31.1 kg; 200-day mass - 135.6, 173.6, 150.6 kg; first calving interval - 474, 441, 685 d; second calving interval - 454, 382, 445 d; calving percentage - 87, 69, 70 %. Birth mass and 200-day mass within breed was affected by sire (p < 0.01). It was concluded that the breeds performed well under drought conditions but performance could be improved by genetic means. (South African Journal of Animal Science, 2000, 30(1): 33)
A survey of goat production in the developing areas of the North West province of South Africa
E. Collins-Lusweti
South African Journal of Animal Science , 2000,
Abstract: The survey was carried out over two years in the Taung and Kudumane districts of the North West Province of South Africa. Data were collected on the breed of goat, reasons for keeping goats as well as production data such as kidding rate, fecundity, herd health care, herd management, live weight and withers height, coat color, skin condition and presence or absence of: beards, horns and wattles. (South African Journal of Animal Science, 2000, 30(1): 34-35)
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