Biomedical subjects
Jason Williams
Publications and source records attributed to Jason Williams.
Occupational autoeczematization or atopic eczema precipitated by occupational contact dermatitis?
Autoeczematization is characterized by the sudden dissemination of a previously localised form of eczema. While widely described, most cases reported have followed chronic, localized stasis dermatitis. In this study, we describe the clinical scenario of occupational contact dermatitis (OCD) triggering endogenous-like eczema in atopic individuals, who often have not had eczema since childhood, if at all. These cases appear similar to previously described cases of autoeczematization. To show this clinical scenario, a series of 6 patients is presented from the Occupational Dermatology Clinic in Melbourne, Australia. These workers initially developed OCD, usually affecting the hands, which then precipitated a flare of more generalized eczema. This appeared clinically consistent with atopic eczema (AE), and often became recurrent, and sometimes persistent. OCD can precipitate a flare of more generalized eczema, in a pattern consistent with AE, which may then persist. The clinical scenario is similar to that described for autoeczematization. It is possible that the pathophysiology, when clarified, will prove to be similar. Workers' compensation issues may become complicated for these patients, as the relationship between their generalized eczema and their occupational exposures may not be readily apparent. As a result, the work relatedness of their condition may not be recognized.
Purified vitamin K epoxide reductase alone is sufficient for conversion of vitamin K epoxide to vitamin K and vitamin K to vitamin KH2.
More than 21 million prescriptions for warfarin are written yearly in the U.S. Despite its importance, warfarin's target, vitamin K epoxide reductase (VKOR), has resisted purification since its identification in 1972. Here, we report its purification and reconstitution. HPC4, a calcium-specific antibody that recognizes a 12-aa tag, was used to purify and identify VKOR. Partial reconstitution is achieved on the column by washing with 0.4% dioleoylphosphatidylcholine/0.4% deoxycholate. Activity is completely recovered by dialysis against a buffer containing a reducing agent but lacking dioleoylphosphatidylcholine/deoxycholate. Removal of detergent from the eluted proteins apparently facilitates liposome formation. Purified recombinant VKOR with tag is approximately 21 kDa, as expected; fully active; and > 93% pure. The concentration of warfarin for 50% inhibition is the same for purified protein and microsomes. It has been reported that VKOR is a multisubunit enzyme. Our results, however, suggest that a single peptide can accomplish both the conversion of vitamin K epoxide to vitamin K and vitamin K to reduced vitamin K. This purification will allow further characterization of VKOR in relation to other components of the vitamin K cycle and should facilitate its structural determination.
Progress toward healthy people 2000 objectives among U.S. military personnel.
OBJECTIVE: Examine progress toward Healthy People 2000 objectives among active-duty military personnel and identify subgroups at risk for not meeting objectives. METHODS: Comprehensive Department of Defense surveys were completed in 1995, 1998, and 2002. Target behaviors were analyzed for achievement of objectives and demographic factors for their relationship to unmet objectives. RESULTS: The military met 7 of 15 objectives assessed in 2002. Achieved objectives, such as drug use, exercise, and safety equipment use, were generally behaviors monitored by military requirements. Unmet risk behavior and health maintenance objectives were related to military demographics, civilian trends, and societal norms. Smoking was more likely not met by enlisted (OR = 2.7, CI = 2.0-3.9), male, white, less educated, younger, single, Army, and Navy personnel. Overweight was more likely not met by male (OR = 3.4, CI = 3.0-4.0), African American, Hispanic, more educated, aged 35 or older, married, enlisted, and Navy personnel. Health maintenance goals were more likely not met by enlisted (OR = 1.5, CI: 1.1-2.2), male, nonwhite, less educated, younger, single, Navy, and Marine personnel. CONCLUSIONS: Objectives are more likely met when regulatory mechanisms encourage compliance. Future studies are needed to understand mechanisms accounting for achievement of objectives. Next steps for unmet objectives are to target interventions for high-risk groups.
Mediators of the stress-substance-use relationship in urban male adolescents.
Exposure to chronic or severe acute stressors throughout the lifespan has been linked with numerous negative behavioral, emotional, cognitive, and physical consequences. Adolescence is considered to be a particularly vulnerable period given that the brain is experiencing dramatic developmental change during this time. The present study examined a sample of adolescents (N=125) considered to be at high risk for stress exposures and drug use by virtue of their environment and low income levels to identify possible neurocognitive (i.e., impulsivity, delay of gratification, emotional perception, and risky decision-making) and social competency mechanisms that may mediate this relationship. Using Mplus, a mediational model was tested using full information maximum likelihood estimates. Risky decision-making and poor social competency skills were related to previous stressful experiences; however, only social competencies mediated the effect of stressors on reports of past year marijuana, alcohol, and polydrug use. As such, stress appears to exert its negative impact through alterations in abilities to generate and execute prosocial decisions and behaviors. Interventions that directly address the effects of stress on social competencies may be especially important for children who have experienced adversity including those exposed to parental divorce, parental psychopathology, neglect or abuse, parental death, and poverty.
A 2-iminohydantoin from the oxidation of guanine.
The nucleobase guanine was oxidized with dimethyldioxirane (DMDO) to explore the role of epoxidizing agents in oxidative DNA damage. Treatment of guanine with 10% molar excess DMDO in aqueous solution at 0 degrees C and pH 7.5 followed by workup under mild conditions gave 5-carboxamido-5-formamido-2-iminohydantoin (1) as the sole isolable product in 71% yield. The structure of 1 was established on the basis of mass spectrometry and NMR studies on 1 and its isotopomers generated by the oxidation of [4-(13)C] and [7-(15)N]guanine, which yield [5-(13)C]1 and [7-(15)N]1. The distribution of 13C and 15N labels in the isotopomeric products supports initial epoxidation of the C4-C5 bond of guanine followed by a 1,2-acyl migration of guanine C6. Compound 1 is suggested as a possible primary DNA lesion from putative epoxidizing agents, including hydroperoxides present during biological processes such as lipid peroxidation.
Allergic contact dermatitis to panthenol and cocamidopropyl PG dimonium chloride phosphate in a facial hydrating lotion.
Dexpanthenol is the alcohol corresponding to pantothenic acid (the water-soluble vitamin B(5)). Although it is a common ingredient in many pharmaceuticals and cosmetics, contact allergy is relatively uncommon. Cocamidopropyl PG dimonium chloride phosphate is a phospholipid complex derived from pure coconut oil, and contact allergy is rare. We report a case of allergic contact dermatitis to panthenol and cocamidopropyl PG dimonium chloride phosphate in a facial hydrating lotion.
Multiple microarray platforms utilized for hepatic gene expression profiling of GH transgenic coho salmon with and without ration restriction.
The objectives of this study are to examine hepatic gene expression changes caused by GH transgenesis and enhanced growth. This is the first use of cDNA microarrays to study the influence of GH transgenesis on liver gene expression in a non-mammalian vertebrate, and the first such study using sexually immature animals. Three groups of coho salmon were examined: GH transgenic on full ration (T), GH transgenic on restricted ration (R), and control non-transgenic (C). Specific growth rates for weight in T were approximately eightfold higher than in C, and fourfold higher than in R. Differential gene expression in T, R, and C samples was determined using approximately 3500 and 16,000 gene microarrays, and R and C samples were compared on a different approximately 4000 gene microarray. The use of multiple microarray platforms increased the overall proportion of the hepatic transcriptome considered in these studies. Cross-platform comparisons identified genes behaving similarly between studies. For example, genes encoding a precerebellin-like protein and complement component C3 were downregulated in R relative to C (R < C) in two microarray studies, and hemoglobins alpha and beta were R > C in all three studies. Comparisons of informative gene lists within and between studies inferred causes of altered gene expression. For example, ten genes, including 78 kDa glucose-regulated protein, glycerol-3-phosphate dehydrogenase, hemoglobins alpha and beta, and a C-type lectin, were likely induced by GH transgenesis due to their presence in both T > C and R > C gene lists. Eleven genes, including hepcidin, nuclear protein p8, precerebellin-like, transketolase, and fatty acid-binding protein, were present in both T < C and R < C gene lists and were, therefore, likely suppressed by GH transgenesis. A large number of salmonid genes identified in these studies are involved in iron homeostasis, mitochondrial function, carbohydrate metabolism, cellular proliferation, and innate immunity. Pentose phosphate pathway genes phosphogluconate dehydrogenase, transaldolase, and transketolase, were dysregulated in GH transgenic samples relative to control samples. Changes in the expression of genes involved in maintaining hemoglobin levels (heme oxygenase, hemoglobins alpha and beta, Kruppel-like globin gene activator, hepcidin) in R and T fish indicate a need for additional hemoglobin in the transgenic fish, perhaps due to higher metabolic rate required for enhanced growth.
Five-year surveillance of West Nile and eastern equine encephalitis viruses in Southeastern Virginia.
To investigate the occurrence of West Nile virus (WNV) and Eastern equine encephalitis virus (EEE) in southeastern Virginia, the Bureau of Laboratories at the Norfolk Department of Public Health (NDPH) analyzed mosquito pools and the sera of sentinel chickens from the southeastern Virginia area each year from 2000 to 2004. Mosquito pool supernatants were screened for the presence of viral RNA by conventional reverse transcription polymerase chain reaction (RT-PCR) and Taqman RT-PCR with the i-Cycler. Mosquito pools were also tested for virus activity by Vero cell culture. The primary enzootic vector of WNV was Culex (Cx.) pipiens and that of EEE was Culiseta (Cs.) melanura. During the five-year surveillance period, the peak minimum infection rates (MIRs) of WNV and EEE in these mosquito species were 2.7 (2002) and 0.9 (2001), respectively. In 2003, the MIRs in Cs. melanura for WNV and EEE were 0.24 and 0.56, respectively; and the MIR for WNV in Cx. pipiens was 0.64. In 2004, Cs. melanura was less active in the WNV transmission cycle (MIR = 0.07) than was Cx. pipiens (MIR = 1.8), and Cs. melanura was the only vector for EEE (MIR = 0.37). The trend was for EEE activity to peak in July; WNV activity peaked in August. Sentinel-chicken sera were tested for IgM antibodies, and peak IgM seroconversions to these arboviruses were recorded in August 2003 for WNV and in July 2003 for EEE. In 2004, the highest IgM seroconversions to EEE occurred later in August. The overall trend of arbovirus activity was greater in 2003 than in 2004.
The Ins(1,3,4)P3 5/6-kinase/Ins(3,4,5,6)P4 1-kinase is not a protein kinase.
Among inositol phosphate kinases, Ins(3,4,5,6)P4 1-kinase has been considered to be an outsider with disparate sequence, a proclaimed capacity to also phosphorylate proteins and apparent 1-phosphatase activity. Such multifunctionality, coupled with ignorance of its operational domains, complicates any mechanistic rationale behind literature reports that Ins(3,4,5,6)P4 1-kinase regulates apoptosis, salt and fluid secretion, and transcription. We have expressed poly(His)-tagged human Ins(3,4,5,6)P4 1-kinase in Sf9 insect cells and purified the enzyme using Ni-agarose chromatography. Protein kinase activity was eluted from the Ni-agarose column, but this did not co-elute with the Ins(3,4,5,6)P4 1-kinase, indicating that the protein kinase and inositol kinase activities belong to separate proteins. To pursue this conclusion, we prepared catalytically inactive mutants of the Ins(3,4,5,6)P4 1-kinase by identifying and targeting the ATP-binding site. Our strategy was based on sequence alignments suggesting homology of the Ins(3,4,5,6)P4 1-kinase with ATP-grasp metabolic enzymes. Individual mutation of four candidate MgATP-binding participants, Lys157, Asp281, Asp295 and Asn297, severely compromised Ins(3,4,5,6)P4 1-kinase activity. Yet, these mutations did not affect the protein kinase activity. We conclude that the Ins(3,4,5,6)P4 1-kinase is not a protein kinase, contrary to earlier reports [e.g. Wilson, Sun, Cao and Majerus (2001) J. Biol. Chem. 276, 40998-41004]. Elimination of protein kinase activity from the enzyme's repertoire and recognition of its ATP-grasp homology together indicate that structural, functional and catalytic relationships between Ins(3,4,5,6)P4 1-kinase and other inositol phosphate kinases are closer than previously thought [Gonzalez, Schell, Letcher, Veprintsev, Irvine and Williams (2004) Mol. Cell 15, 689-701].
Analysis of baseline by treatment interactions in a drug prevention and health promotion program for high school male athletes.
This paper investigates baseline by treatment interactions (BTI) of a randomized anabolic steroid prevention program delivered to high school football players. Baseline by treatment interactions occur when a participant's score on an outcome variable is associated with both their pretreatment standing on the outcome variable and the treatment itself. The program was delivered to 31 high school football teams (Control=16, Treatment=15) in Oregon and Washington over the course of 3 years (Total N=3207). Although most interactions were nonsignificant, consistent baseline by treatment interactions were obtained for knowledge of the effects of steroid use and intentions to use steroids. Both of these interactions were beneficial in that they increased the effectiveness of the program for participants lower in knowledge and higher in intentions at baseline.
Identification of genes differentially expressed in Atlantic salmon (Salmo salar) in response to infection by Aeromonas salmonicida using cDNA microarray technology.
The response of Atlantic salmon, Salmo salar, to infection by the bacterial pathogen Aeromonas salmonicida (the causative agent of furunculosis), was investigated using a cohabitation model and a custom Atlantic salmon cDNA microarray consisting of over 4000 different amplicons. Pooled samples of each of three immune-relevant tissues (spleen, head kidney and liver) were obtained from fish exposed to infected salmon for 13 days. Reverse transcription-PCR assays were used to verify the differential expression of 12 candidate genes uncovered by microarray analysis. Among the differentially expressed genes were several previously revealed by suppression subtractive hybridization and EST surveys and that are recognized to encode humoral components of the innate immune system. Other genes identified in this study were not previously associated with infection. In addition, a number of genes with no known homologs were uncovered. Determination of their specific roles during infection may lead to a better understanding of innate immunity.
The vascular basis of the thoracodorsal artery perforator flap.
BACKGROUND: Musculocutaneous perforator flaps, or more simply, perforator flaps, have become increasingly popular in microsurgery because of numerous advantages, including reduced donor-site morbidity. The thoracodorsal artery perforator flap is a cutaneous flap based on cutaneous perforators of the thoracodorsal vessels. The objective of this study was to document the vascular anatomy of this flap in human cadaveric studies. METHODS: The anatomy of the perforators of the thoracodorsal artery was studied using a modified lead oxide-gelatin injection technique in 15 fresh human cadavers. Each fresh cadaver was injected with lead oxide, gelatin, and water, and then cooled to 4 degrees C for 24 hours before dissection. The torso was dissected to identify all cutaneous perforators in the region of the back and flank. RESULTS: The mean area of the primary and secondary zones supplied by the thoracodorsal artery was 255 cm2 and 345 cm2, respectively. The mean length of the major and minor axes was 18 cm and 13 cm, respectively. The maximum dimensions of the skin that could potentially be supplied by the thoracodorsal artery averaged 600 cm2, with a major axis length of 28 cm and a minor axis length of 27 cm. A mean number of 5.5 perforators with a mean diameter of 0.9 mm (range, 0.5 to 1.5 mm) supplied this zone. The ratio of musculocutaneous to septocutaneous perforators from the thoracodorsal artery was 3:2. The length of the thoracodorsal pedicle when harvested along with the perforator was 14.0 cm, with the vessel diameter being 2.8 mm at the origin. The most proximal perforator was seen at the level of the inferior angle of the scapula, 3.0 cm medial to the anterior border of the muscle. The intramuscular course of the perforators averaged 5 cm (range, 3 to 7 cm). Septocutaneous perforators from the thoracodorsal artery supplying the skin in addition to the musculocutaneous perforators were seen in 60 percent of specimens. CONCLUSIONS: The thoracodorsal artery perforator flap is a reliable cutaneous perforator flap that is very useful in a wide variety of clinical applications.
Three small, cryptic plasmids from Aeromonas salmonicida subsp. salmonicida A449.
The nucleotide sequences of three small (5.2-5.6 kb) plasmids from Aeromonas salmonicida subsp. salmonicida A449 are described. Two of the plasmids (pAsa1 and pAsa3) use a ColE2-type replication mechanism while the third (pAsa2) is a ColE1-type replicon. Insertions in the Rep protein and oriV region of the ColE2-type plasmids provide subtle differences that allow them to be maintained compatibly. All three plasmids carry genes for mobilization (mobABCD), but transfer genes are absent and are presumably provided in trans. Two of the plasmids, pAsa1 and pAsa3, carry toxin-antitoxin gene pairs, most probably to ensure plasmid stability. One open reading frame (ORF), orf1, is conserved in all three plasmids, while other ORFs are plasmid-specific. A survey of A. salmonicida strains indicates that pAsa1 and pAsa2 are present in all 12 strains investigated, while pAsa3 is present in 11 and a fourth plasmid, pAsal1, is present in 7.
Survey of the use of suction drains in head and neck surgery and analysis of their biomechanical properties.
BACKGROUND: Closed suction drains have an important role in surgical wound healing. Although most surgeons use them routinely, indications for use and their postoperative management (emptying, removal) vary. The purpose of this study was to assess drain use by head and neck surgeons in Canada, to conduct a biomechanical analysis of the drains in a laboratory setting, and to make recommendations for drain use and management. METHODS: A survey was mailed to 343 active members of the Canadian Society of Otolaryngology. Three sets of experimental trials were conducted on the most commonly used drains to assess the effect of increased reservoir filling on suction generated through (1) incrementally increasing the amount of fluid within the reservoir, (2) compression of the reservoir with no fluid within, and (3) compression with the reservoirs while filled to 25% capacity with fluid. RESULTS: A 41% response rate was obtained. It was found that the majority of head and neck surgeons in Canada use Hemovac and Jackson-Pratt drainage systems routinely. There is considerable variability in practice with regard to drain emptying and timing of removal. Experimental results indicate that as filling of the reservoir increases, suction generated decreases sharply, to between 13 and 20% of initial values at 50% capacity. CONCLUSION: Postoperative drain management has important implications in surgical wound healing. Drain reservoirs should be monitored frequently to ensure adequate compression, particularly in the first 24 hours after insertion. Anticipated volume of drainage should dictate in part which reservoir is chosen. A larger reservoir is preferable in most cases. Drains should be removed promptly to decrease the risk of wound contamination.
Enhancing the validity of foster care follow-up studies through multiple alumni location strategies.
While family-based placement prevention services, family reunification programs, subsidized guardianship, and aggressive adoption programs are reducing the numbers of children spending long periods of time in substitute care, a significant number of America's children will come of age in foster care. Agencies and policymakers should use research and evaluation to assess the effectiveness of foster care in nurturing healthy adults and to explore ways to improve services. Outcome studies that have focused on locating and interviewing young or middle-aged adults emancipated from foster care have been hampered by modest response rates, limiting the field's ability to evaluate the efficacy of foster care programs. This article describes a set of strategies that were used to achieve higher response rates in two recent follow-up studies.