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Biomedical subjects

David W Wright

Publications and source records attributed to David W Wright.

At least 19 recordsLinked to original sources
PubMed2005

Ubiquitin and ubiquitin-derived peptides as substrates for peptidylglycine alpha-amidating monooxygenase.

Ubiquitin (Ub) and the ubiquitin-like proteins (UBLs) mediate an array of cellular functions. These proteins contain a C-terminal glycine residue that is key to their function. Oxidative conversion of C-terminal glycine-extended prohormones to the corresponding alpha-amidated peptide is one step in the biosynthesis of bioactive peptide hormones. The enzyme catalyzing this reaction is peptidylglycine alpha-amidating monooxygenase (PAM). We report herein that Ub is a PAM substrate with a (V/K)(amidation) that is similar to other known peptide substrates. This work is significant because PAM and the UBLs co-localize to the hypothalamus and the adrenal medulla and are both over-expressed in glioblastomas.

Amino Acid Sequence↗
PubMed2005

Progesterone treatment inhibits the inflammatory agents that accompany traumatic brain injury.

Progesterone given after traumatic brain injury (TBI) has been shown to reduce the initial cytotoxic surge of inflammatory factors. We used Western blot techniques to analyze how progesterone might affect three inflammation-related factors common to TBI: complement factor C3 (C3), glial fibrillary acidic protein (GFAP), and nuclear factor kappa beta (NFkappaB). One hour after bilateral injury to the medial frontal cortex, adult male rats were given injections of progesterone (16 mg/kg) for 2 days. Brains were harvested 48 h post-TBI, proteins were extracted from samples, each of which contained tissue from both the contused and peri-contused areas, then measured by Western blot densitometry. Complete C3, GFAP, and NFkappaB p65 were increased in all injured animals. However, in animals given progesterone post-TBI, NFkappaB p65 and the inflammatory metabolites of C3 (9 kDa and 75 kDa) were decreased in comparison to vehicle-treated animals. Measures of NFkappaB p50 showed no change after injury or progesterone treatment, and progesterone did not alter the expression of GFAP. The therapeutic benefit of post-TBI progesterone administration may be due to its salutary effect on inflammatory proteins known to increase immune cell invasion and cerebral edema.

Analysis of Variance↗
PubMed2005

beta-Hematin (hemozoin) mediated decompostion of polyunsaturated fatty acids to 4-hydroxy-2-nonenal.

beta-Hematin is an important heme metabolite of malarial infection. Its role as an agent mediating the formation of the reactive electrophile 4-hydroxynonenal (HNE) from polyunsaturated fatty acids was investigated. In vitro formation of HNE was found to be facilitated by the presence of hemozoin in a concentration-dependent fashion. The reactivity of HNE derived from reaction with beta-hematin was confirmed through its ability to form protein adducts on myoglobin.

Aldehydes↗
PubMed2005

Size control of dendrimer-templated silica.

One of the most significant challenges facing the biomimetic synthesis of materials is achieving the requisite level of dimensional and spatial control. Typical reaction conditions for biomimetic silica synthesis allow for continued growth and ripening leading to the formation of larger nanospheres on the order of 200-600 nm in diameter. Herein, we have used polyamidoamine and polypropylenimine dendrimers as templates to expand the reaction conditions of biogenic silica production to produce a more robust synthesis leading to size-selective precipitation of silica nanospheres. Through the use of defined concentrations of phosphate buffer and main group metal chloride salts, we have shown that the biomimetic silica growth process is controlled by cationic neutralization of the anionic silica nanosphere surface. Neutralization minimizes electrostatic repulsions, allowing for agglomerization and continued growth of nanospheres. By controlling these concentrations, we can selectively produce silica nanospheres of desired dimensions between 30 and 300 nm without adversely affecting the template's activity.

Chemical Precipitation↗
PubMed2005

Quartz crystal microbalance detection of glutathione-protected nanoclusters using antibody recognition.

A quartz crystal microbalance (QCM) immunosensor was developed for the quantitative detection of glutathione-protected nanoclusters. Advantages intrinsic to QCM were employed to make it an attractive alternative to other immunosensing techniques. We have addressed challenges in the area of QCM mass sensing through experimental correlation between damping resistance and frequency change for a reliable mass measurement. Electrode functionalization was optimized with the use of protein A to immobilize and present polyclonal IgG for antigen binding. This method was developed for the detection of glutathione (antigen)-protected clusters of nanometer size with high surface area and thiolate valency. Quantitation of glutathione-nanocluster binding to immobilized polyclonal antibody provides equilibrium constants (K(a) = (3.6 +/- 0.2) x 10(5) M(-1)) and kinetic rate constants (k(f) = (5.4 +/- 0.7) x 10(1) M(-1) s(-1) and k(r) = (1.5 +/- 0.4) x10(-4) s(-1)) comparable to literature reports. These observations further imply that immunoreactive nanoparticles have potential in medical diagnostics and materials assembly.

Antibodies↗
PubMed2005

Progression of respiratory syncytial virus infection monitored by fluorescent quantum dot probes.

We report the use of quantum dots (QDs) to identify the presence and monitor the progression of respiratory syncytial virus (RSV) infection over time by labeling the F and G proteins. In addition, co-localization of these viral proteins was shown using confocal microscopy. The implications of these results are that QDs may provide a method for early, rapid detection of viral infection and open the door for future studies of the intricate spatial features cell trafficking of viral proteins.

Cell Line↗
PubMed2005

Supervisees' perspectives of power use in supervision.

In this study, we examined the use of power in the supervisory relationship from supervisees' perspectives. Semistructured interviews of 11 supervisees in a Commission on Accreditation for Marriage and Family Therapy Education training program were conducted. From analysis of interview transcripts, themes about the ways in which supervisors and supervisees used power in the supervisory relationship emerged. Supervisors' power uses included discussions of power, empowering supervisees, promoting an atmosphere of safety, collaborating with supervisees, imposition of style/orientation, and misuses of power, such as violation of confidentiality. Themes for supervisees' power uses included supervisee-peer power, supervisees as consumers, and withholding information. Implications for researchers, supervisors, and supervisees are presented.

Adult↗
PubMed2005

Steady-state serum concentrations of progesterone following continuous intravenous infusion in patients with acute moderate to severe traumatic brain injury.

Progesterone (PG) has been shown to provide substantial neuroprotection after traumatic brain injury (TBI) in multiple animal models. As a first step in assessing applicability to humans, the authors examined the effects of acute TBI and extracranial trauma on the pharmacokinetics of PG given by intravenous infusion. Multiple blood samples were obtained from 11 female and 21 male trauma patients receiving PG and 1 female and 3 male patients receiving placebo infusions for 72 hours. Values for C(SS), CL, t(1/2), and Vd were obtained using AUC((0-72)) and postinfusion blood samples. C(SS) values were 337 +/- 135 ng/mL, which were significantly lower than the target concentration of 450 +/- 100 ng/mL. The lower C(SS) is attributed to the CL, which was higher than anticipated. In addition, t(1/2) was longer and V(d) was higher than anticipated. These results demonstrate that stable PG concentrations can be rapidly achieved following TBI.

Area Under Curve↗
PubMed2005

Assays for selection of single-chain fragment variable recombinant antibodies to metal nanoclusters.

The protocols herein describe colony-lift and fluorescent immunoassays that were used to identify bacterial colonies that produced single-chain fragment variable (ScFv) recombinant antibodies reactive with zero-state silver. A large (approx 2.9-billion member) phage-displayed antibody library was panned against zero valent silver. Bacterial colonies obtained after two rounds of selection were either lifted onto nitrocellulose filters or picked to individual wells of 384-well microtiter culture plates. Colonies lifted onto filters were placed onto zero valent silver-coated filters and induced to produce soluble ScFv antibodies. ScFv antibodies, expressed by individual colonies, that bound to silver nanocluster-coated filters were detected using an anti-ScFv antibody conjugated to horseradish peroxidase and a chemiluminescent substrate. Colonies picked to 384-well micotiter culture plates were induced to express soluble ScFv antibodies. ScFv antibodies in bacterial periplasmic extract were transferred from 384-well culture plates to 384-well assay plates containing zero-state silver particles and an anti-ScFv antibody conjugated to a fluorescent dye. ScFv antibodies, expressed by individual bacterial clones, that bound to zero valent silver nanoparticles in 384-well assay plates were detected using an FMAT 8100 fluorescent plate reader. The colony-lift and fluorescent immunoassays detected ScFv antibodies reactive with zero valent silver. Similar assay formats should also be useful to detect bacterially expressed recombinant antibodies or proteins to other nanoclusters.

Animals↗
PubMed2005

Screening of combinatorial Peptide libraries for nanocluster synthesis.

A significant challenge in bionanotechnology is the discovery of effective biological interfaces that allow inorganic nanoscale materials to mimic effectively their biological counterparts. Much like de novo design of proteins, the rational design of such interfaces is a daunting task. An alternative approach is to screen libraries of peptides, inspired by known biological examples of such hybrid protein-material interfaces, for peptide ligands capable of not only stabilizing a size-discrete population of nanoclusters, but providing the requisite biological compatibility. The protocol described in this chapter is an approach for the simultaneous screening of spatially addressable combinatorial libraries for the stabilization of a variety of metal sulfide, metal oxide, and zero-valent nanoclusters. Additionally, the screening process allows the researcher to characterize the resulting nanoclusters in terms of a variety of physical properties. Ultimately, an informatics structure-function analysis may be performed in order to elucidate specific properties of the ligand sets, which provides access to certain desired material characteristics.

Animals↗
PubMed2004

Amine-terminated dendrimers as biomimetic templates for silica nanosphere formation.

In diatoms, silica synthesis occurs by use of complex posttranslationally modified peptides, termed silaffins, and highly complex biological polyamine structures. Silaffin peptides have lysine residues that are modified to long-chain polyamine moieties of N-methyl derivatives of polypropylenimine to drive silica synthesis at slightly acidic pH conditions. Using polypropylenimine (PPI) and PAMAM amine-terminated dendrimers as a biomimetic analogue of the polyamine modifications of silaffins, we have demonstrated the condensation of silica nanospheres. We have shown that the dendrimers react in an amine concentration-dependent fashion yielding silica nanospheres with a distinct size distribution reminiscent of the structures produced from both the modified and nonmodified peptides extracted from diatoms. Additionally, the templates were encapsulated by the growing nanospheres and precipitated from solution in a manner similar to that previously described for the bioactive peptides and polyamines.

Amines↗
PubMed2004

National practice guidelines for mental health care: a comparative policy analysis of the United kingdom and the United States.

Mental disorders are the leading cause of disability worldwide, according to the World Health Organization (WHO, 1996). In a report on health indicators of premature death and disability, the World Bank concluded that mental health problems account for 8.1% of the global burden of disease (GBD). Industrialized nations have taken different approaches in applying innovations to mental health care and mental health care policy. This paper uses the K. McInnis-Dittrich model of policy analysis (Ginsberg, 1994) to analyze the approaches of the United Kingdom (U.K.) and the United States (U.S.) to mental health treatment, specifically examining the effects of the U.K.'s national practice guidelines and the U.S.'s lack of similar guidelines. Recommendations for changes in current U.S. mental health policy are presented.

Health Planning Guidelines↗
PubMed2004

Proxy identification: a time-dependent analysis.

OBJECTIVES: To describe the availability of next-of-kin (NOK) for proxy consent over the 24-hour time period following presentation of major trauma patients to a Level I trauma center. METHODS: The study was conducted by using a prospective, observational study design. Consecutive patients meeting predefined major trauma criteria during a three-month study period were enrolled and followed until NOK were contacted, or up to 24 hours. Survival analysis was used to determine the probability of NOK contact during the 24-hour follow-up period. RESULTS: Three hundred fifty (92%) of 382 subjects had NOK contacted during the follow-up period. The probabilities (95% confidence intervals [CIs]) of NOK contact at the time of arrival (t = 0) and 2, 4, 6, and 24 hours postpresentation were 0.25 (95% CI = 0.21 to 0.30), 0.68 (95% CI = 0.63 to 0.72), 0.77 (95% CI = 0.73 to 0.82), 0.80 (95% CI = 0.76 to 0.84), and 0.87 (95% CI = 0.84 to 0.90), respectively. The median time to contact was 40 minutes (95% CI = 27 to 54 min). CONCLUSIONS: One third of the trauma patients in this study did not have NOK available two hours following arrival in the emergency department. For time-critical research protocols, the time to NOK contact can significantly impact the ability to ensure prompt enrollment and treatment in clinical trials. Further studies are needed to assess the generalizability and consistency of these data.

Adult↗
PubMed2004

Shedding new light on the "safe" club drug: methylenedioxymethamphetamine (ecstasy)-related fatalities.

OBJECTIVES: To report the pathology, toxicology, cause, and manner of death in 3,4-methylenedioxymethamphetamine (MDMA)-associated fatalities in the United States. Although use trends are increasing, data regarding the hazards of MDMA are limited. METHODS: The authors obtained fatality reports from participating medical examiners in the United States. Cases were identified as "drug-unrelated" when MDMA did not directly cause death (e.g., motor vehicle collision); deaths from drug toxicity were judged "drug-related." RESULTS: Thirty-eight (8%) of the surveyed medical examiners reported 102 deaths associated with MDMA use from 1999 to 2001. Ten percent of fatalities occurred in 1999 and 90% thereafter, representing a 400% relative increase. Victims tended to be young (mean age = 25), white (n = 87 [85%]), male (n = 70 [69%]), and otherwise healthy. Seventy-one (70%) deaths were drug-related (DR) and 31 (30%) were drug-unrelated (DU). Twenty-four (35%) DR deaths had a mean delay of 6.7 hours (95% CI = 5.1 to 8.2) in activating emergency medical services. Fifty-five DR cases (81%) were found in asystole and pronounced dead at the scene. CONCLUSIONS: The MDMA-associated fatal events typically occur in young, otherwise healthy individuals. MDMA's impact on the public health and safety of young adults and teenagers needs further assessment.

Adolescent↗
PubMed2003

Metalloporphyrin probes for antimalarial drug action.

Metal-substituted protoporphyrin IXs (Co(III)PPIX (1), Cr(III)PPIX (2), Mn(III)PPIX (3), Cu(II)PPIX (4), Mg(II)PPIX (5), Zn(II)PPIX (6) and Sn(IV)PPIX (7)), phthalocyanine tetrasulfonates (PcS (8) and Ni(II)PcS (9)), and anionic and cationic porphyrins (meso-tetra(4-sulfonatophenyl)porphine (TPPS4, 10), meso-tetra(4-carboxyphenyl)porphine (TPPC4, 11), tetrakis(4-N-trimethylaminophenyl)porphine (TMAP, 12) and meso-tetra(N-methyl-4-pyridyl)porphine (TMPyP4, 13)) have been used as probes to compare two different assays for the inhibition of beta-hematin formation. The results demonstrate that the efficacy of these probes in either the beta-hematin inhibition assay (9, 7, 6, 5>4>11, 3>10, 8>2, 1; 12 and 13 did not inhibit.) or the bionucleating template assay (8>1>11>9, 2>4>3>7>10>5>6; 12 and 13 did not inhibit.) differ significantly. These differences are examined in light of possible interactions between the inhibitor probes, heme, beta-hematin and the bionucleating template. This detailed analysis highlights the fact that while dominant modes of interactions may be occasionally identified, the precise mechanism of inhibition undoubtedly consists of the interplay between multiple interactions.

Antimalarials↗