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David J White

Publications and source records attributed to David J White.

14 recordsLinked to original sources
PubMed2006

Design of base metal extractants. Part 1. Inter-ligand hydrogen bonding in the assembly of pseudo-macrocyclic bis(aminosulfonamidato)M(II) complexes.

Monosulfonyl derivatives of simple 1,2- and 1,3-diamines (R2HN-R-NHSO2R1 = L) have been shown to be easily deprotonated to give neutral 2:1 complexes, [M(L - H)(2)], with Co(II), Ni(II), Cu(II) or Zn(II). The Ni(II) and Cu(II) complexes with deprotonated N-tosyl-1,2-diaminoethane have a planar N4(2-) donor set and a 14-membered pseudo-macrocyclic structure based on head-to-tail S=O...H-N((amine)) bonding between the two bidentate ligands. In the related tetrahedral Zn(II) complex the ends of the mutually perpendicular bidentate N2- units are too far apart to form a cyclic H-bonded system. X-Ray structure determinations on five free ligands provide evidence for extensive inter-molecular H-bonding, which in the case of N-tosyl-1,3-diaminopropane and its N'-tert-butyl derivative involves formation of dimeric 16-membered pseudo-macrocycles. Despite favourable inter-ligand H-bonding in the neutral 2:1 complexes, these ligands are relatively weak extractants, showing >50% loading of Cu(II) in "pH-swing" equilibria, 2L(org)+ M2+ = [M(L - H)2](org)+ 2 H+, only when the pH of the aqueous phase is raised above 4.

Crystallography, X-Ray↗
PubMed2006

The role of anti-non-Gal antibodies in the development of acute humoral xenograft rejection of hDAF transgenic porcine kidneys in baboons receiving anti-Gal antibody neutralization therapy.

BACKGROUND: The present study was undertaken to determine the role of preformed and induced anti-non-Gal antibodies in the rejection of hDAF pig-to-baboon kidney xenotransplants after anti-Gal antibody neutralization therapy. METHODS: Seven baboons received life-supporting kidney transplants from hDAF transgenic pigs. Anti-Gal antibodies were neutralized by GAS914 or TPC (a Gal PEG glycoconjugate polymer). Group 1 (n=5) underwent a conventional immunosuppressive therapy with FK506, rabbit anti-thymocyte serum/immunoglobulin, mycophenolate mofetil, and steroids. Group 2 (n=2) received an anti-humoral immunity regimen with LF15-0195, Rituxan and cobra venom factor in addition to ATG, FK506 and steroids. Levels of anti-non-Gal antibodies and their mediated complement-dependent cytotoxic activities (CDC) were detected by flow cytometry using Gal knockout (k/o) pig lymphocytes (LC) or endothelial cells (EC) as targets. RESULTS: Continuous infusion of GAS914/TPC significantly reduced anti-Gal antibodies. In Group 1, four of five baboons developed severe acute humoral xenograft rejection (AHXR) and the rejection was associated with either a high level of preformed anti-non-Gal IgG or a marked elevation in induced anti-non-Gal IgG and IgM. Sera collected at the time of AHXR had a high level of CDC to porcine LC/EC from Gal k/o animals. The intensive anti-humoral therapy in Group 2 completely inhibited both anti-Gal and non-Gal antibody production and prevented AHXR. However, this therapy was not well tolerated by the baboons. CONCLUSION: In a pig-to-baboon kidney transplant model, both preformed and induced anti-non-Gal antibodies are strongly associated with the pathogenesis of AHXR when anti-Gal antibodies are neutralized.

Acute Disease↗
PubMed2006

Developmental origins of sociality in brown-headed cowbirds (Molothrus ater).

Five variables were studied relating to the emergence of sociality in hand-reared cowbirds (Molothrus ater): proximity, sex assortment, reactions to adults, head-down displays, and vocalizations. The authors were especially interested in female sociality because adult female birds influence male courtship, song content, and use through proximity, attention, and displays. The authors found that young female birds failed to show same-sex affiliation typical of the species at any point in the study. Brief introduction of adults did not affect social patterns. Adults used more head-down displays than juveniles, who used more displays with familiar peers. Directed and undirected singing emerged concurrently; directed singing was positively correlated with earlier hatching. This is the first demonstration of the need for early learning in the development of female sociality.

Age Factors↗
PubMed2005

Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys.

We transplanted kidneys from alpha1,3-galactosyltransferase knockout (GalT-KO) pigs into six baboons using two different immunosuppressive regimens, but most of the baboons died from severe acute humoral xenograft rejection. Circulating induced antibodies to non-Gal antigens were markedly elevated at rejection, which mediated strong complement-dependent cytotoxicity against GalT-KO porcine target cells. These data suggest that antibodies to non-Gal antigens will present an additional barrier to transplantation of organs from GalT-KO pigs to humans.

Animals↗
PubMed2005

The influence of baseline expression of human decay accelerating factor transgene on graft survival and acute humoral xenograft rejection.

BACKGROUND: Transgenic pigs expressing human decay accelerating factor (hDAF) have been widely used as donors in various non-human primate transplant models. Despite the use of similar immunosuppressive protocols, there is marked variation in graft survival among centres. The present study was undertaken to determine whether the level of hDAF expression in the pig kidney correlates with the degree of rejection and duration of graft survival. METHODS: hDAF transgenic pigs were provided from two suppliers: Guelph Imutran Centre (G) and Harlan Sprague Dawley (H). Following a bilateral nephrectomy, a single hDAF pig kidney was implanted in the baboon, which was subsequently treated with conventional immunosuppressive protocols. The pig's contralateral kidney was collected to provide baseline data. The severity of acute humoral xenograft rejection (AHXR) was graded as stage I-III. hDAF expression was measured using morphologic analysis comparing the contralateral and grafted kidneys at the endpoint. RESULTS: Baseline hDAF expression in kidneys from pigs provided by supplier G was significantly higher than that from supplier H (P<0.01). Furthermore, the survival of baboons receiving grafts from G pigs was significantly longer than those receiving grafts from H pigs (P<0.05). In addition, reduction of hDAF expression at the endpoint was associated with a higher degree of AHXR. Severe apoptosis or necrosis was found in grafts with AHXR II-III. CONCLUSIONS: Pig kidneys from different suppliers have variable baseline hDAF expression, which may have an influence on graft survival. Reduced expression of hDAF in the terminal graft was associated with the severity of rejection.

Acute Disease↗
PubMed2004

Lopinavir/ritonavir combined with twice-daily 400 mg indinavir: pharmacokinetics and pharmacodynamics in blood, CSF and semen.

OBJECTIVES: To evaluate the steady-state blood plasma (BP), CSF and seminal plasma (SP) pharmacokinetics (PK) of twice-daily indinavir 400 mg and lopinavir/ritonavir. METHODS: Ten HIV-1-positive men on lopinavir/ritonavir participated in a PK study. PK sampling was performed before and 2 weeks after adding indinavir to lopinavir/ritonavir-containing regimens. BP, CSF and SP RNA levels, CD4 counts and blood chemistry were checked at baseline and 2 weeks after indinavir. RESULTS: At baseline: lopinavir parameters (n=10) in BP were within expected levels. Median lopinavir trough concentrations (n=5) in CSF and SP were below the limit of detection (BLD) (i.e. <10 ng/mL) and 248 ng/mL (range 96-2777), respectively. After indinavir: lopinavir C(max), C(min) and AUC(0-12) increased by 9%, 46% and 20%, respectively (P<0.32, P<0.32 and P<0.20). In two of four men lopinavir concentrations in CSF were detectable at 27 and 29 ng/mL. Median SP lopinavir concentration was 655 ng/mL (20-2734). Median indinavir PK parameters were C(max) 3365 ng/mL (range 2130-5194), C(min) 293 ng/mL (14-766), T(max) 2.25 h (1-3), AUC(0-12) 22452 ng/mL.h (11243-33661), and t(1/2) 2.8 h (1.4-3.7). Median indinavir concentrations in CSF and SP were 39 ng/mL (21-86) and 592 ng/mL (96-983). Two of eight men who initially had detectable BP viral load (VL) became BLD (<50 copies/mL) after the addition of indinavir, and in 2/4 men with low-level viraemia in SP (BPVL BLD) their SPVL became BLD after addition of indinavir. CONCLUSIONS: Adding indinavir 400 mg twice daily to lopinavir/ritonavir-containing regimens did not significantly alter the median lopinavir PK parameters. However, wide interpatient variability in lopinavir concentrations was seen. In contrast plasma indinavir levels were >80 ng/mL in seven of eight plasma samples, and all CSF and semen samples collected.

Adult↗
PubMed2004

Patterns of treatment and resource utilization in the treatment of external genital warts in England and Wales.

Our objective was to identify patterns of treatment and resources used in achieving complete clearance of external genital warts (EGWs) A retrospective case note review was carried out at six genitourinary medicine (GUM) clinics in the UK. Case notes from 2366 patients presenting with EGWs were reviewed and 1200 patients with complete episodes of care were identified. Analysis showed that staff-applied therapy dominated treatment practice but there was considerable diversity in treatment modalities across study sites. The average number of visits was 5.71 visits for males: 6.25 visits for females but a substantial minority of patients attended significantly in excess of these averages. Approximately two-thirds of patients failed to achieve complete clearance of warts with their initial therapy. There is little consistency in treatment patterns of care for EGWs across the sites studied. Initial therapy choices are largely ineffective, requiring changes in treatment modality and multiple clinic visits. Increased utilization of patient-applied therapies might result in increased cost effectiveness.

Adult↗
PubMed2004

The costs of treating external genital warts in England and Wales: a treatment pattern analysis.

The objective of the study was to determine the cost implications of patterns of treatment for patients with external genital warts. A retrospective case note review was carried out at six genitourinary medicine (GUM) clinics in the UK. Significant variations in the total costs of care were observed across the clinics and across the choice of therapy. The cost per successful outcome was pound 221.81 for males and pound 211.07 for females. A minority of patients accounted for the majority of costs, for example the 30.1% of male patients who recorded six or more visits contributed 66.2% of the total cost. Costs also varied significantly by therapy sequence chosen. Patients who remained on their initial therapy experienced the lowest costs, with the extent to which patients shifted therapies substantially impacting on costs. Therapy sequences involving podophyllin were found to be the most expensive options in achieving a completed episode of care. We concluded that a high proportion of costs for GUM clinics is due to the failure of the initial therapy and by subsequent therapy switching. A greater emphasis on the selection of alternative treatment options, such as the patient-applied therapies, may help to reduce overall costs of care.

Ambulatory Care Facilities↗
PubMed2004

Influences of social learning on mate-choice decisions.

Evidence from both field and laboratory is consistent with the hypothesis that animals can acquire mate preferences by observing the mating behavior of others. It is difficult, however, to distinguish social learning about mates from a host of other social effects on mating that do not produce changes in preferences. Examples are drawn from laboratory studies on mate choice in female and male Japanese quail that illustrate ways in which social cues influence mating decisions. Quail of both sexes use social cues to modify their mate choices, but the sexes use the information to serve different purposes. Female quail gain preferences for males seen mating with other females, whereas males avoid females that they had observed mating with other males. This sex difference in social learning provides an example of how costs and benefits of sexual behavior can shape decision-making processes. Implications of the influence of social learning on sexual selection are briefly discussed.

Adaptation, Psychological↗
PubMed2003

Identification of genes required for adventurous gliding motility in Myxococcus xanthus with the transposable element mariner.

Myxococcus xanthus glides over solid surfaces without the use of flagella, dependent upon two large sets of adventurous (A) and social (S) genes, using two different mechanisms of gliding motility. Myxococcus xanthus A-S- double mutants form non-motile colonies lacking migratory cells at their edges. We have isolated 115 independent mutants of M. xanthus with insertions of transposon magellan-4 in potential A genes by screening for insertions that reduce the motility of a mutant S- parental strain. These insertions are found not only in the three loci known to be required for A motility, mglBA, cglB, and aglU, but also in 30 new genes. Six of these new genes encode different homologues of the TolR, TolB, and TolQ transport proteins, suggesting that adventurous motility is dependent on biopolymer transport. Other insertions which affect both A and S motility suggest that both systems share common energy and cell wall determinants. Because the spectrum of magellan-4 insertions in M. xanthus is extraordinarily broad, transposon mutagenesis with this eukaryotic genetic element permits the rapid genetic analysis of large sets of genes that contribute to a complex microbial behaviors such as A motility.

DNA Transposable Elements↗
PubMed2003

LF15-0195 generates tolerogenic dendritic cells by suppression of NF-kappaB signaling through inhibition of IKK activity.

LF15-0195 (LF) is a potent, less toxic analog of the immunosuppressant 15-deoxyspergualine, which we previously reported to prevent graft rejection and to induce permanent tolerance in a murine cardiac transplantation model. However, the underlying mechanism of action of LF required elucidation. In this study, dendritic cells (DC) treated with LF before activation with tumor necrosis factor alpha (TNF-alpha)/lipopolysaccharide (LPS) failed to express maturation markers (major histocompatibility complex II, CD40, CD86) and interleukin-12. LF prevented, in a concentration-dependent manner, the activation and nuclear translocation of nuclear factor-kappaB (NF-kappaB) in DC following addition of TNF-alpha/LPS. Yet-activated and active IkappaB kinases (IKKs) were inhibited in cells pretreated with LF, thereby preventing the phosphorylation of IkappaB and release of NF-kappaB, a key regulator of genes associated with the maturation of DC. LF-induced inhibition of IKK activity was reversed in a dose-dependent manner by the overexpression of IKK. The T helper cell type 2 (Th2) differentiation of naïve T cells promoted by LF-treated DC in vitro correlates with Th2 polarization observed in transplant recipients made tolerant by LF. These data demonstrated that LF-induced blockade of NF-kappaB signaling at the level of IKK promoted the generation of tolerogenic DC that inhibited Th1 polarization and increased Th2 polarization in vitro and in vivo.

Animals↗
PubMed2002

The presumption of sociality: social learning in diverse contexts in brown-headed cowbirds (Molothrus ater).

Data are presented on social and vocal learning in cowbirds (Molothrus ater) housed in large aviaries and given more degrees of freedom than in conventional experimental studies. The studies show that social and vocal outcomes are facultative responses to social contexts. Several findings are reviewed: First, cowbirds quickly self-organize into groups by age and sex; second, opportunities to interact across age and sex do exist and affect courtship competence; third, female cowbirds organize themselves differently in the presence and absence of male competition; and fourth, young, naive cowbirds show rapid and differential sensitivity to group dynamics. Taken as a whole, the data show that social Umwelten are dynamic, developmental ecologies.

Age Factors↗
PubMed2002

Voice recognition technology as a tool for behavioral research.

Behavioral research often requires the acquisition and processing of large volumes of data. Most current techniques for recording behavior constrain the amount and type of data that can be measured. We developed and tested a system that uses voice recognition technology to collect data on the social interactions and singing patterns of cowbirds (Molothrus ater) living outdoors in a semi-natural environment. We spoke observation data into a wireless microphone that transmitted the data to a computer in the laboratory. After collection, the data were automatically checked for errors and then were entered into a database. Overall, the system performed at extremely high levels of accuracy. Furthermore, owing to the removal of constraints on observers such as breaking visual contact with subjects and manual data entry into a database, we were able to increase the amount of data collected and to collect new measures of social interactions that have not been available to us in the past. We tested the system under the challenging circumstances of field observation, and it performed above our expectations. In a laboratory setting, if transmission difficulties are removed, voice recognition could be even more accurate. We recommend voice recognition as a powerful new tool for the variety of research fields in which measuring behavior is involved.

Animals↗