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Biomedical subjects

J D Wright

Publications and source records attributed to J D Wright.

At least 37 records · Page 2Linked to original sources
PubMed1999

Serum total homocysteine concentrations in adolescent and adult Americans: results from the third National Health and Nutrition Examination Survey.

BACKGROUND: The elevation of circulating total homocysteine concentrations in a fasting state is associated with an increased risk of occlusive vascular disease. OBJECTIVE: The primary goals of this study were to describe the distribution of serum total homocysteine concentrations in the United States and to test for differences in homocysteine concentrations among sex, age, and race-ethnicity categories. DESIGN: Using surplus sera from phase 2 of the third National Health and Nutrition Examination Survey, we measured serum total homocysteine concentrations for a nationally representative sample of 3766 males and 4819 females aged > or = 12 y. RESULTS: Age-adjusted geometric mean total homocysteine concentrations were 9.6 and 7.9 mmol/L in non-Hispanic white males and females, 9.8 and 8.2 mmol/L in non-Hispanic black males and females, and 9.4 and 7.4 mmol/L in Mexican American males and females, respectively. Age-adjusted geometric mean total homocysteine concentrations were significantly lower in females than in males in each race-ethnicity group (P < 0.01) and were significantly lower in Mexican American females than in non-Hispanic white and non-Hispanic black females (P < 0.01). There was a significant age-sex interaction (P < 0.01), reflecting the fact that homocysteine concentrations in females tended to diverge from those in males at younger ages and converge with those in males at older ages. CONCLUSIONS: The first data on homocysteine concentrations in a nationally representative sample of Americans confirm the age and sex differences reported previously in nonrepresentative samples. These data also indicate that differences between Mexican American and non-Hispanic females may influence circulating homocysteine concentrations.

Adolescent↗
PubMed1999

Use of dietary supplements in the United States, 1988-94.

OBJECTIVES: This report presents estimates of the prevalence of use of dietary supplements among the U.S. population by various demographic and descriptive characteristics, the number of products taken, and types of supplements taken by broad product-type categories. METHODS: The third National Health and Nutrition Examination Survey (NHANES III) is a nationally representative survey of the civilian, noninstitutionalized U.S. population, 2 months of age or over. Participants were asked about their use of vitamin and/or mineral supplements in the past month. Many also reported use of other dietary supplements. RESULTS: Approximately 40 percent of the population took dietary supplements during the month prior to the interview. Females (44 percent) were more likely to take a supplement than males (35 percent). Non-Hispanic white persons (43 percent) were more likely to take supplements than non-Hispanic black persons (30 percent) and Mexican American persons (29 percent). Children 1-5 years of age were major users of supplements. Among adults 20 years of age and older, there was a trend toward increasing use of dietary supplements with age. Higher levels of education, income, and self-reported health status were all positively related to supplement use. Sixty-seven percent of supplement users took only one supplement, with the majority of them taking a combination vitamin/mineral product (46 percent). CONCLUSIONS: A substantial proportion of the U.S. population takes vitamins, minerals, and/or other dietary supplements.

Adolescent↗
PubMed1998

Prediction of an anti-IgE binding site on IgE.

A combination of computation techniques have been used to determine the binding site and amino acid residues on IgE that are critical for binding to a therapeutic anti-IgE. Homology modeling was used to model parts of IgE and of an antibody that binds to IgE. Docking simulations using shape descriptions were then carried out using the models to determine which residues in the IgE are involved in the binding interaction. The anti-IgE has been determined to bind close to some of the residues that are believed to be in the Fc(epsilon)RI receptor site on IgE, therefore preventing IgE from binding to Fc(epsilon)RI on mast cells and basophils and causing the release of pharmacologic mediators from these cells. Experiments have been suggested to verify the binding site and the residues involved in binding to anti-IgE.

Amino Acid Sequence↗
PubMed1998

Blood folate and vitamin B12: United States, 1988-94.

OBJECTIVES: This report presents national estimates of serum and red blood cell (RBC) folate and serum vitamin B12 distributions for persons 4 years and over, by sociodemographic variables. METHODS: The third National Health and Nutrition Examination Survey (NHANES III) (1988-94), provides information on the health and nutritional status of the civilian noninstitutionalized U.S. population. The analytic sample included 23,378 participants with serum folate data, 23,082 with RBC folate data, and 11,851 with serum vitamin B12 data. RESULTS: The mean serum and RBC folate concentrations are 7.2 and 196 nanograms per milliliter (ng/mL), respectively, and the mean serum vitamin B12 concentration is 518 picograms per milliliter (pg/mL). Non-Hispanic white people have higher mean serum and RBC folate concentrations than non-Hispanic black or Mexican American people. Serum vitamin B12 concentrations are lowest for older adults, and non-Hispanic black people have higher serum B12 concentrations than non-Hispanic white individuals. Only approximately 3 percent of the population has a serum B12 concentration less than 200 pg/mL. CONCLUSIONS: Inadequate folate status may be more prevalent among non-Hispanic black and Mexican American people. Data also suggest a modest prevalence of low serum B12 concentrations. Future assessments of folate and vitamin B12 status will be important to evaluate the impact of a recently enacted fortification policy.

Adolescent↗
PubMed1997

Losing the housing game. The leveling effects of substance abuse.

Analysis of the housing dynamics and individual characteristics of a sample of 670 participants in the New Orleans Homeless Substance Abusers Program reveals substantial diversity with respect to income, education, and occupational attainment. Nevertheless, drug consumption and dependence serve as socioeconomic levelers, dissolving otherwise potentially critical differences in human-capital and economic capacities. The need to focus concurrently on both structural and individual causes of homelessness is emphasized.

Employment↗
PubMed1997

Substance use among street children in Honduras.

The hypothesis that drug use among Honduran street children is a function of developmental social isolation from cultural and structural influences is examined. Data from 1,244 children working and/or living on the streets of Tegucigalpa are described, separating "market" children from "street" children. The latter group is then divided into those who sniff glue and those who do not to identify salient distinguishing factors. An OLS regression of drug usage on these variables results in a model that explains 75% of the variance, where family relations, length of time on the street, and delinquency are the most important factors.

Adolescent↗
PubMed1996

Identification of sites on epidermal growth factor receptors which are phosphorylated by pp60src in vitro.

The Epidermal Growth Factor Receptor (EGF-R) becomes constitutively tyrosine phosphorylated on two novel sites in v-Src transformed cells, and these phosphorylations are associated with enhanced signaling activity [1]. To determine whether Src could directly phosphorylate these sites, we have examined the ability of the Src kinase to phosphorylate both wild-type and kinase-defective EGF-Rs in vitro. Although purified Src could phosphorylate EGF-Rs, the pattern of phosphorylation sites was not identical to what was previously found in vivo [1]: Src in vitro directly phosphorylated EGF-Rs on one autophosphorylation site (Tyr 1173) which was not a site of re-induced in vivo phosphorylation, suggesting the in vivo inaccessibility of this site. One Src-specific in vitro phosphorylation site (Tyr 03) appeared to correspond to one of the in vivo Src-induced sites (sPY2), but the other Src-specific in vivo site (sPY1) was not significantly phosphorylated in vitro, raising the possibility of a Src-induced tyrosine kinase cascade. The ability of Src to phosphorylate the EGF-R is consistent with the suggestion that the receptor can function as a kinase substrate independent of its intrinsic enzymatic activity, as implied by recent studies on signaling by kinase-defective EGF-Rs.

Amino Acid Sequence↗
PubMed1996

Discontinuous oral absorption pharmacokinetic model and bioavailability of 1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl)uracil (L-FMAU) in rats.

1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl)uracil (L-FMAU), the L isomer of FMAU, has shown potent activity against hepatitis B virus and Epstein-Barr virus. L-FMAU showed double peaks in the plasma concentration versus time profiles following oral administration to rats, indicating discontinuous oral absorption. The objective of this study was to characterize the bioavailability and pattern of L-FMAU absorption using a pharmacokinetic model which incorporated two separate absorption processes following oral administration of the nucleoside in an animal model, the rat. Simultaneous fitting of differential equations to L-FMAU plasma concentrations following oral and intravenous administration was performed using PCNONLIN. Total clearance of L-FMAU was moderate, averaging 0.47 +/- 0.16 L h-1 (mean +/- SD). Distributional clearance averaged 0.18 +/- 0.14 L h-1. The volume of the central compartment averaged 0.30 +/- 0.09 L, and the volume of the peripheral compartment averaged 0.15 +/- 0.08 L. The first-order absorption rate constants describing the first and second absorption phases averaged 1.22 +/- 1.56 and 4.14 +/- 5.42 h-1, respectively. Oral bioavailability was calculated by three methods: AUC, urinary excretion data, and a discontinuous oral absorption pharmacokinetic model. Bioavailability averaged 0.59 +/- 0.16, 0.64 +/- 0.23, and 0.63 +/- 0.13, respectively, for the three methods. The discontinuous oral absorption pharmacokinetic model is a promising new method for estimating absorption from two phases and for calculating oral bioavailability.

Absorption↗
PubMed1996

A retrospective evaluation of the surgical management of equine carpal injury.

Records of 220 thoroughbred horses presented to the Randwick Equine Centre or the University of Queensland Veterinary Teaching Hospital for surgical management of carpal injury were reviewed. Details of racing performance were obtained, enabling evaluation of racing success following surgery. Age and sex matched control horses not known to have suffered carpal injury were selected from the Australian Stud Book and the Australian Racehorse Register. Control and treated populations were compared in terms of overall career racing success. Radiographs or xeroradiographs from 198 horses were available for evaluation. The dorsomedial aspects of the distal articular surface of the radial carpal bone and the proximal articular surface of the third carpal bone were the most commonly observed locations of osteochondral fracture. Bilateral carpal injury was found to be sufficiently common to warrant routine radiographic examination of both limbs. The dorsolareral-palmaromedial oblique, flexed lateral and dorsoproximal-dorsodistal oblique (skyline) projections were the most useful views for evaluation of carpal degenerative joint disease. Surgical removal of osteochondral fractures by arthrotomy or arthroscopy was found to be a suitable method of treatment. Arthroscopy was associated with a significantly shorter convalescent period than arthrotomy. Seventy-six percent of the treated population returned to racing following surgery. Average earnings following surgery were $20,000. However, the median value was only $1400 and 48% of the treated population failed to earn more than $1000. Male horses in both the treated and control groups performed significantly better than females. Treated horses performed significantly better than the randomly selected control population.

Animals↗
PubMed1996

Measurement and analysis of unbound drug concentrations.

The plasma protein binding of drugs has been shown to have significant effects on numerous aspects of clinical pharmacokinetics and pharmacodynamics. In many clinical situations, measurement of the total drug concentration does not provide the needed information concerning the unbound fraction of drug in plasma which is available for distribution, elimination, and pharmacodynamic action. Thus, accurate determination of unbound plasma drug concentrations is essential in the therapeutic monitoring of drugs. Many methodologies are available for determining the extent of plasma protein binding of drugs, however, in the clinical evaluation of drug therapy, equilibrium dialysis and ultrafiltration are the most routinely utilised methods. Both of these methods have been proven to be experimentally sound and to yield adequate protein binding data. Furthermore, the characterisation of the interactions between drug and protein molecules is essential for the assessment of the pharmacokinetic implications of drug-protein binding. Protein binding parameters which characterise the affinity of the drug-protein association, the number of classes of binding sites, the number of binding sites per class or protein and the binding capacity are useful for predicting unbound drug concentrations. Simple graphical methods have often been used to obtain protein binding parameters, but these methods have limitations and are not useful for drugs with more than 1 class of binding site. Therefore, the fitting of protein binding models which characterise the drug-protein binding interaction for experimental data is the preferred method of calculating binding parameters. Using the appropriate model, values for binding parameters are typically estimated by using nonlinear least-squares regression analysis.

Blood Proteins↗
PubMed1996

Reliability and validity of the addiction severity index among homeless substance misusers.

Retrospective self-reports of behavior are widely used in alcohol and drug research. However, assessments of the reliability and validity of such data among certain populations are nonexistent. This study examines the ability of the Addiction Severity Index (ASI), a widely used clinical and research instrument, to provide valid and reliable data within a homeless population of drug misusers. The results support the usefulness of the ASI in producing quality data among homeless substance misusers seeking treatment. Qualitative data gathered from field interviewers are used to highlight strategies for enhancing the quality of ASI data in the future.

Adult↗
PubMed1995

An incomplete program of cellular tyrosine phosphorylations induced by kinase-defective epidermal growth factor receptors.

Although signaling by the epidermal growth factor (EGF) receptor is thought to be dependent on receptor tyrosine kinase activity, it is clear that mitogen-activated protein (MAP) kinase can be activated by receptors lacking kinase activity. Since analysis of the signaling pathways used by kinase-defective receptors could reveal otherwise masked capabilities, we examined in detail the tyrosine phosphorylations and enzymes of the MAP kinase pathway induced by kinase-defective EGF receptors. Following EGF stimulation of B82L cells expressing a kinase-defective EGF receptor mutant (K721M), we found that ERK2 and ERK1 MAP kinases, as well as MEK1 and MEK2 were all activated, and SHC became prominently tyrosine-phosphorylated. By contrast, kinase-defective receptors failed to induce detectable phosphorylations of GAP (GTPase-activating protein), p62, JAK1, or p91STAT1, all of which were robustly phosphorylated by wild-type receptors. These data demonstrate that kinase-defective receptors induce several protein tyrosine phosphorylations, but that these represent only a subset of those seen with wild-type receptors. This suggests that kinase-defective receptors activate a heterologous tyrosine kinase with a specificity different from the EGF receptor. We found that kinase-defective receptors induced ErbB2/c-Neu enzymatic activation and ErbB2/c-Neu binding to SHC at a level even greater than that induced by wild-type receptors. Thus, heterodimerization with and activation of endogenous ErbB2/c-Neu is a possible mechanism by which kinase-defective receptors stimulate the MAP kinase pathway.

Adaptor Proteins, Signal Transducing↗