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Biomedical subjects

B Watkins

Publications and source records attributed to B Watkins.

At least 19 recordsLinked to original sources
PubMed2006

Gene expression changes in peripheral blood cells provide insight into the biological mechanisms associated with regimen-related toxicities in patients being treated for head and neck cancers.

UNLABELLED: Patients treated with radiotherapy are prone to a constellation of local and systemic toxicities including mucositis, xerostomia, fatigue and anorexia. The biological complexities and similarities underlying the development of toxicities have recently been realized. Mucosal barrier injury is one of the best studied, and gene expression patterns, based on animal tissue samples, have added to its understanding. While investigations gene expression based on tissue samples was valuable, its use precludes more generalizable conclusions relative to common pathogenic mechanisms. Additionally, attempting to define the kinetics of changes in gene expression by sequential sampling is pragmatically unrealistic. Our objectives were: 1. to determine if changes in gene expression could be detected during toxicity development using PBM from patients receiving chemoradiation; 2. to characterize the relationship of expressed genes using graph theory and pathway analysis; and 3. to evaluate potential relationships between the expression of particular genes, canonical pathways, and functional networks in explaining the pathogenesis of regimen-related toxicities. DESIGN: Microarray analysis was performed using PBM-derived cRNA obtained before and 2 weeks after the initiation of chemoradiation in five patients with head and neck cancer who developed documented regimen-related toxicities. We created a database of those genes newly expressed at 2 weeks and evaluated their potential significance relative to toxicity, by canonical pathway analysis, compilation of regional networks around focus genes, and development of a model globalizing the individual functional networks. There was strong concordance between known pathogenic mechanisms of toxicity and the genes, pathways, and networks developed by our data. A role was elicited for unsuspected genes in toxicity development. Our results support the concept that radiation induced toxicities have common underlying mechanisms and demonstrate the utility of PBM as an RNA source for genetic studies. This methodology could be broadly applicable to the study of regimen-related toxicities.

Adult↗
PubMed2005

Human fibroblast growth factor 20 (FGF-20; CG53135-05): a novel cytoprotectant with radioprotective potential.

The aim was to evaluate the radioprotective properties of recombinant human fibroblast growth factor 20 (FGF-20; CG53135-05) in vitro and in vivo and to examine its effects on known cellular pathways of radioprotection. Relative transcript levels of the cyclooxygenase 2 (COX2), Mn-super oxide dismutase (SOD), CuZn-SOD, extracellular (EC)-SOD, nuclear respiratory factor 2 (Nrf2), glutathione peroxidase 1 (GPX1) and intestinal trefoil factor 3 (ITF3) genes, which are involved in radiation response pathways, were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) in NIH/3T3, IEC18, CCD-18Co, CCD-1070sk and human umbilical vein endothelial cells (HUVEC) cells exposed to FGF-20. Activation of the radioprotective signal transduction pathways initiating with the serine/threonine Akt kinase and the extracellular regulated kinase (ERK) were analysed. Levels of intracellular hydrogen peroxide and cytosolic redox potential were also measured in irradiated and unirradiated cells in the presence or absence of FGF-20. The effects of FGF-20 on cell survival in vitro following ionizing radiation were evaluated using clonogenic assays. To test the potential activity of FGF-20 as a radioprotectant in vivo, mice were administered a single dose of FGF-20 (4 mg kg(-1), intraperitoneally (i.p.) 1 day before lethal total-body irradiation and evaluated for survival. In vitro exposure to FGF-20 increased expression of the Nrf2 transcription factor and oxygen radical scavenging enzymes such as MnSOD, activated signal transduction pathways (ERK and Akt) and resulted in increased survival of irradiated cells in vitro. FGF-20 treatment also resulted in a concomitant reduction in intracellular levels of injurious reactive oxygen species (ROS) following acute ionizing irradiation. Finally, prophylactic administration of FGF-20 to mice before potentially lethal, whole-body X-irradiation led to significant increases in overall survival. FGF-20 reduced the lethal effects of acute ionizing radiation exposure in cells by up-regulating important signalling and free radical scavenging pathways. Survival-sparing effects of FGF-20 prophylaxis in acutely irradiated mice presumably are elicited by comparable mechanisms. These results indicate that FGF-20, has significant radioprotective attributes with potential applications in clinical and non-clinical exposure settings.

Animals↗
PubMed2002

The nosological status of early onset anorexia nervosa.

BACKGROUND: Although cases of early onset anorexia nervosa have been described, there has been no systematic comparison of early onset cases with classic cases of later onset, or with other forms of early onset eating disturbance. METHOD: A consecutive series of patients referred to two specialist child and adolescent eating disorder services with a clinical diagnosis of eating disorder (N = 126) was systematically assessed using a child version of the Eating Disorder Examination (EDE) and the K-SADS interview. RESULTS: Of 86 patients with a diagnosis of eating disorder of early onset, 38 received a clinical diagnosis of anorexia nervosa (AN). The remainder were mainly diagnosed as having food avoidance emotional disorder (25 patients) and selective eating (17 patients). Six received other diagnoses (bulimia nervosa, or functional dysphasia). These 48 patients were combined to form a group of early onset non-AN eating disturbance. In terms of specific eating disorder psychopathology and general psychopathology, the early onset AN group was very similar to the late onset AN sample. When the two early onset groups were compared, there was a marked difference between them in terms of eating disorder psychopathology. A discriminant function analysis using the EDE information produced a clear discrimination, with the EDE restraint and shape concern subscales doing most of the discrimination work. CONCLUSIONS: The specific psychopathology of AN of early onset is very similar to that of classic adolescent onset AN. Other forms of early onset eating disorder do not evidence this specific psychopathology.

Adolescent↗
PubMed2001

Is physical illness a risk factor for eating disorders in children and adolescents? A preliminary investigation.

This study investigates the correlation between early-onset eating disorders and past history of physical illness. Subjects for this study were children and adolescents aged between 7 and 19 years, and were divided into two groups: those with anorexia nervosa (n=62) and those with "other eating disorders" (n=28). Data on medical history were obtained retrospectively from the patient's files and coded by a consultant psychiatrist. There was no significant difference between the two groups in relation to a history of prior physical illness. However, those with anorexia nervosa were significantly more likely to have suffered more than one serious physical illness prior to the onset of their eating disorder, and both groups were significantly more likely to have had a prior physical illness than an adult control group [Patton, G. C., Wood, K., & Johnson-Sabine. Br. J. Psychiatry 149 (1986) 756.]. Thus, it appears that a past history of physical illness is a significant risk factor for early-onset eating disorders in general, and for anorexia nervosa in particular when there has been more than one physical illness.

Journal Article↗
PubMed2000

Economic feasibility analysis for an automated on-line poultry inspection technology.

On-line carcass inspection of chickens in the United States is currently done using visual (organoleptic) methods. Inspectors from the USDA Food Safety and Inspection Service (FSIS) inspect the viscera and carcass and, for older birds, the heads using a sequence of observations and palpations at a postmortem inspection station. The streamlined inspection system (SIS) and the new line speed inspection system (NELS) are the most prevalent visual inspection methods. The former has a line speed of 70 birds/min with two inspectors per line, and the latter has a line speed of 91 birds/min requiring three inspectors per line. Both inspection methods are labor intensive and prone to human error. In addition, the speed of the slaughter line is dictated by the number of birds per minute that can be inspected by FSIS inspectors. Ninety-one birds/min is currently the maximum visual inspection line speed allowed under current Federal regulations. This study evaluates the economic benefits of using automated inspection in place of visual inspection from the perspective of both the slaughter plant and FSIS. The results indicate that FSIS and slaughter plants would gain economic benefits by using automated inspection in place of visual inspection. The economic benefits to FSIS would accrue from labor savings, whereas the economic benefits to slaughter plants would accrue primarily from increased throughput from faster inspection line speeds.

Abattoirs↗
PubMed1998

Posterior to anterior transglenoid pins: anatomy at risk.

Pneumothorax was noted after an arthroscopic procedure during which a small guidewire overpenetrated the glenoid from a posterior-superior direction. This anatomic study was undertaken to determine the structures at risk from pins overpenetrating from the posterior-superior aspect and to determine whether scapulothoracic position altered the risk. The glenoid was intentionally overpenetrated with wooden dowels from the posterior-superior aspect of the glenoid in seven fresh cadaveric shoulders. The dowels were placed arthroscopically using the Suretac instrumentation (Acufex Microsurgical, Mansfield, MA). The specimens were planed, and the relationship of these wooden pins to vital structures was evaluated. In all specimens, the dowels entered the thoracic cavity between the first and second ribs, regardless of scapular position. The pins consistently passed posterior to the neurovascular bundle but were precariously close, with an average distance to the closest neurovascular structure of 7.4 mm (range, 1 to 19 mm). Scapular position did not seem to affect this relationship.

Adult↗
PubMed1996

Opportunities for the testing of environmental transport models using data obtained following the Chernobyl accident.

The aftermath of the Chernobyl accident has provided a unique opportunity to collect data sets specifically for the purpose of model testing, and with these data to create scenarios against which environmental transport models may be tested in a format constituting a blind test. This article serves as an introduction to three test scenarios designed for testing models at the process level: (1) surface water contamination with radionuclides initially deposited onto soils; (2) contamination of different aquatic media and biota due to fallout of radionuclides into a body of water; and (3) atmospheric resuspension of radionuclides from contaminated land surfaces. These scenarios are the first such tests to use data sets collected in the former Soviet Union. Interested modelers are invited to participate in the test exercises by making calculations for any of these test scenarios. Information on participation is included.

Models, Biological↗
PubMed1995

The structure, response properties and development of a hair plate on the mesothoracic leg of the locust.

A hair plate is present on the proximal anterior face of the pro- and mesothoracic tibiae of the legs of the locust Schistocerca gregaria, but not on the metathoracic legs. The hair plate is in a depression of the cuticle and contains about 11 hairs, which are all polarised with their tips pointing towards the dorsal surface of the tibia. The hairs are all of the same trichoid sensilla type and vary in length from 90 to 140 microns. Associated with the hair plate is a pronounced distal extension of the anterior femoral coverplate, the inner face of which is concave, that makes contact with the hairs during flexion and extension movements of the tibia. During postembryonic development, no tibial hair plate hairs are present in the first four larval stages. In fifth-instar larvae just three hairs are present, while the full complement is attained only after the final moult to adulthood. The distal extension of the posterior coverplate is present through all instar stages, becoming more pronounced after each moult. Sensory neurones innervating the hairs of an adult may be divided into two classes on the basis of their responses. The first type responds phasically to imposed deflections and is velocity-sensitive. The second type responds phasotonically and is also sensitive to the velocity of the stimulus but has an additional tonic component sensitive to maintained angular deflections. Both types of afferents are directionally sensitive and respond best to deflections against the natural bend of the hair, equivalent to extension movements of the tibia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

HMO marketing and selection bias: are TEFRA HMOs skimming?

The research evidence indicates that health maintenance organizations (HMOs) participating in the Tax Equity and Fiscal Responsibility Act of 1982 (TEFRA) At-Risk Program tend to experience favorable selection. Although favorable selection might result from patient decisions, a common conjecture is that it can be induced by HMOs through their marketing activities. The purpose of this study is to examine the relationship between HMO marketing strategies and selection bias in TEFRA At-Risk HMOs. A purposive sample of 22 HMOs that were actively marketing their TEFRA programs was selected and data on organizational characteristics, market area characteristics, and HMO marketing decisions were collected. To measure selection bias in these HMOs, the functional health status of approximately 300 enrollees in each HMO was compared to that of 300 non-enrolling beneficiaries in the same area. Three dependent variables, reflecting selection bias at the mean, the low health tail, and the high health tail of the health status distribution were created. Weighted least squares regressions were then used to identify relationships between marketing elements and selection bias. Subject to the statistical limitations of the study, our conclusion is that it is doubtful that HMO marketing decisions are responsible for the prevalence of favorable selection in HMO enrollment. It also appears unlikely that HMOs were differentially targeting healthy and unhealthy segments of the Medicare market.

Advertising↗
PubMed1992

The sexual abuse of male children and adolescents: a review of current research.

Inevitably, in a wide ranging review, there will be some important omissions. The main difficulties in assessing the available information have been the lack, in so many studies, of analysis along gender lines, the lack of control groups, and, in many instances, too small sample size. Despite these limitations there has, over the past decade, been an upsurge of interest in and awareness of the significance of the sexual abuse of boys. It permits us to identify a number of important trends and to draw certain conclusions. Firstly, the scale of the sexual abuse of boys is much greater than was believed 10 years ago. There is no reason to think this is simply an artifact of definition, or information gathering, or indeed of an increased willingness to recognize abusive behaviour between children, even though these will all have an effect. Whilst the trend is clear, the actual prevalence rate is difficult to determine, with a reported range of between 3% and 31%. A current 'best guess' suggests contact abuse in the range of 2-5% in the male population. As each study controls for its own definition of abuse, the narrowing in the ratio of boys to girls abused can be accepted as quite reliable, and additional evidence of a delayed recognition effect. Retrospective community evidence shows 1 boy is abused for every 2-4 girls abused. In contrast, the highest clinical ratios are for 1 boy to every 4 girls. Those who work with runaways, male child prostitutes, or child and adolescent psychiatric inpatient units appear particularly likely to encounter abused boys. Secondly, a variety of explanations have been advanced to explain the apparent under-reporting or under-detection of the sexual abuse of boys. Prominent among them have been the boy's fears of disbelief and of being labelled homosexual. Police patterns of reporting extra-familial abuse may mask its extent from protection or health agencies, which is important because extra-familial abuse does appear to be more common in boys, especially older boys, than girls. Although there has been some diminution of the cultural denial that girls can be abused, a parallel decrease of denial regarding boys has lagged behind. This is particularly true of father-son and of the much less common mother-son abuse. It is plausible that certain 'alertors' are more relevant for boys. The recent development of aggressive behaviour, homophobic anxiety, co-abuse of a sibling and abusing behaviour in particular deserve consideration.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

Identification of bull protamine disulfides.

We have identified the disulfide cross-links in bull protamine by titrating intact bull sperm with dithiothreitol (DTT) and following the modification of each cysteine residue with tritiated iodoacetate. The derivatization of each cysteine was monitored by a combination of HPLC, peptide mapping, and protein sequencing. Analyses of total free sulfhydryls show that all seven of the bull protamine cysteines are cross-linked as disulfides in mature sperm. The first disulfide is reduced at a DTT:protamine cysteine (DTT:Cys) ratio of 0.3 and the last at a ratio of 2.0. Intra- and intermolecular disulfides were identified by correlating the reduction of specific disulfides with the dissociation of protamine from DNA in partially reduced sperm and sperm treated with N,N'-ethylenedimaleimide, a bifunctional disulfide cross-linking agent. Three intermolecular and two intramolecular disulfides were identified. The results of these experiments demonstrate that the amino- and carboxy-terminal ends of the bull protamine molecule are folded inward toward the center of the molecule and are locked in place, each by a single intramolecular disulfide bridge. Three intermolecular disulfides cross-link neighboring protamine molecules around the DNA helix in such a manner that the protamines cannot be dissociated from DNA without first reducing the interprotamine disulfides.

Amino Acid Sequence↗
PubMed1990

The influence of gut microorganisms on zinc uptake in Helix aspersa.

An artificial diet was prepared that enabled the snail Helix aspersa to be fed food containing varying amounts of metals, antibiotics or bacteria. By this means it is possible to show that the body burden of zinc was significantly correlated with the dietary intake. The snail was, however, able to detect high concentrations of the metal and reduced its intake of such contaminated food. The bacterial population of the alimentary tract modified the amount of zinc absorbed from the diet. It appears, therefore, that biological monitoring programmes, based upon bioaccumulation measurements, should take these influences into account.

Journal Article↗
PubMed1989

A high-resolution, fluorescence-based, semiautomated method for DNA fingerprinting.

We describe a fluorescence-based method for the automated analysis of DNA fragments on polyacrylamide gels. A single-stranded oligonucleotide primer (18-mer) with a fluorochrome covalently bound to its 5'-end is annealed to a synthetic oligonucleotide to create a double-stranded oligonucleotide linker with a 5'-overhang complementary to a restriction enzyme site. Cosmid or plasmid DNA is digested with the appropriate restriction enzyme and then ligated to the fluorochrome-labeled linker. The labeled restriction fragments are loaded on a denaturing polyacrylamide gel in a commercially available DNA sequencer. As the restriction fragments migrate through the gel, they intersect a laser beam which excites the fluorochrome-labeled fragment. Fluorescence emission data are captured on a computer in real time and analyzed after the completion of electrophoresis. Fragment length is nearly linearly related to migration time. This method offers very near single-base resolution up to 400 bases and the ability to quantitate fragment size up to 2000 bases. The fluorochrome-labeling chemistry relies on straightforward enzymatic reactions and can be performed in a single reaction tube. Because four different fluorochromes can be used, each of 16 lanes on the gel can be used to analyze four different digest reactions, one in each color. One of the fluorochromes can be used to label size standards in each lane, eliminating interlane variability and allowing more precise estimates of fragment size. We apply the method to the analysis of overlapping cosmids.

Animals↗
PubMed1989

Conceptions of athletic excellence among children and adolescents.

Youth in grades 3, 6, 9, and 12 were interviewed about their beliefs regarding athletic excellence. A set of open-ended questions assessed beliefs about the source of athletic ability and the differences between excellent athletes and others. Respondents also rated excellent athletes on a checklist containing various physical, cognitive, emotional, and interpersonal traits. Younger children were less likely than adolescents to differentiate excellent athletes. All participants, but especially adolescents, attributed greater physical skills to highly competent athletes. All but the third graders thought excellent athletes were different from others in terms of cognitive skills (e.g., attention, concentration), and adolescents believed excellent athletes also differed from others in terms of attitudes (e.g., motivation, determination). Older males were more likely to believe that athletic excellence was due to natural ability, whereas older females were more likely to attribute excellence to early social support and facilitation.

Adolescent↗
PubMed1988

Effects of temperature oscillations on the distribution of 65Zn on cytoplasmic proteins.

1. Oscillating temperatures cause an increase in 65Zn uptake into the digestive gland of M. edulis when compared with the effects of constant temperatures. 2. The increased uptake is associated with a change in the distribution of 65Zn onto cytoplasmic proteins. There is a fall in the percentage of metal on the greater than 70 K dalton fraction and a rise in the 3 K dalton fraction. 3. A possible hypothesis is produced to explain these effects in terms of heat lability of metal-protein ligands.

Animals↗
PubMed1987

Monoclonal antibodies for dioxin: antibody characterization and assay development.

A set of 5 anti-dioxin monoclonal antibodies (mAbs), named DD-1, DD-3, DD-4, DD-5 and DD-6, have been isolated. In order to evaluate the ability of these mAbs to recognize various kinds of polychlorinated dibenzodioxins and dibenzofurans, a competition enzyme-linked immunosorbtion assay (ELISA) was developed. All 5 antibodies recognize tetrachloro- and pentachloro-dibenzodioxins and -dibenzofurans. They fail to bind either non-chlorinated, mono-, hexa-, or octa-chlorinated dibenzodioxins, nor do they recognize non-chlorinated, octachloro- or 1,2,3,4,8,9-hexachloro-dibenzofurans. Chlorine substitution on both rings appears necessary for antibody recognition. In the course of our experiments, 3 of the mAbs did not recognize any of the polychlorinated biphenyls (PCBs) tested, while 2 mAbs (DD-1 and DD-6) weakly recognized the 3,3',4,4'-tetrachloro congener. DD-4 and DD-5 are the most specific of the antibodies for the dibenzodioxin and dibenzofuran structure. They do not recognize any of a panel of chlorinated phenols, benzenes, or pesticides. Significantly, these antibodies do not react with PCBs, pentachlorophenol, 2,4-dichlorophenoxyacetic acid, trichlorophenol, or 2,4,5-trichlorophenoxyacetic acid (the latter is weakly recognized by DD-6), any or all of which might be present in large quantities in some dioxin-contaminated samples. Finally, the competition ELISA is able to easily detect 0.5 ng of the most toxic dioxin congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin. It should thus prove useful as an environmental screen for contamination.

Animals↗