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Biomedical subjects

C Walker

Publications and source records attributed to C Walker.

At least 217 records · Page 12Linked to original sources
PubMed1993

Pregnancy outcome among women exposed to pesticides through work or residence in an agricultural area.

The study population consisted of women enrolled in a southern California community clinic perinatal program. All women entering the program between January 1987 and December 1989 were asked to participate, and a cohort of 535 women was included in the study. Primarily Hispanic, of low income and educational level, many had recently immigrated from Mexico. They were potentially exposed to pesticides and other agricultural chemicals occupationally and/or environmentally because agricultural production in San Diego County is among the highest in the state. Study methods consisted of biologic assay of maternal blood samples for determination of cholinesterase activity and concurrent patient interviews to determine exposure history by self report. These assessments were conducted on each participant approximately once each trimester. Self-report and blood assay data were analyzed using chi 2, the Mantel-Haenszel extension of chi 2, and risk ratios to determine the association between pesticide exposure and spontaneous abortion, preterm birth, low birth weight and toxemia. No difference between exposed and unexposed women was noted for risk of preterm birth or toxemia. Subjects who experienced spontaneous abortion were all unexposed, and the rate of spontaneous abortion was 2.1%, less than generally expected. A greater incidence of low birth weight among unexposed women indicates that exposure may have had a "protective" effect.

Abortion, Spontaneous↗
PubMed1993

Atopic dermatitis: correlation of peripheral blood T cell activation, eosinophilia and serum factors with clinical severity.

In the first part of this study peripheral blood lymphocyte subpopulations, their activation state and various serum parameters were measured in extrinsic and intrinsic atopic dermatitis (AD) patients compared to normal individuals. Beside the characteristic eosinophilia, significantly increased numbers of CD4+ T cells with increased expression of IL-2 receptors (IL-2R) and HLA-DR were noted in the AD patients. In addition, extrinsic AD patients showed increased numbers of CD23+ B cells and decreased numbers of CD16+ natural killer cells. Moreover, increased serum levels of eosinophil cationic protein (ECP) and soluble IL-2R as well as soluble factors that prolong survival of eosinophils in vitro could be demonstrated. In the second section of this study we determine how these blood immunological parameters relate to the clinical severity of the skin lesions of AD, by weekly analysis of 12 AD patients attending a high altitude clinic for 3 to 6 weeks. The patients were divided into two groups on the basis of treatment with topical steroids, but during the observation period a significant improvement in clinical status was observed in all AD patients independent of topical steroid therapy. A progressive decrease in eosinophil and activated T cell numbers, soluble IL-2R levels and serum eosinophil survival prolonging activity could be demonstrated, which closely correlated with the clinical severity of the AD.

Adolescent↗
PubMed1993

Lack of increased numbers of low-density eosinophils in the circulation of asthmatic individuals.

The density distribution pattern of eosinophils over discontinuous isotonic Percoll gradients from the blood of normal, asymptomatic allergic and non-allergic asthmatic individuals was investigated. There was a completely identical distribution pattern between the investigated groups. Analysis of the expression of surface markers for complement receptors CR1 and CR3 and immunoglobulin G receptor on eosinophils derived from the density bands 1.080, 1.085 and 1.090 g/ml supported this finding since they did not reveal differences in expression between the bands within one group but also not between the three groups. Eosinophils of the various density bands were further purified and stimulated in vitro to produce leukotriene C4 (LTC4) by the calcium ionophore A23187 or serum treated zymosan. Equal amounts of LTC4 were synthesized by the eosinophils of the various density bands within one group. However, it appeared that the eosinophils of all density bands of allergic and non-allergic asthmatics synthesized significantly more LTC4 than the eosinophils from normal individuals (five- to tenfold). Probably this indicates in vivo priming of the eosinophils in asthmatic individuals which is not reflected by a change in density. Control experiments, dealing with possible artifacts due to the isolation procedure or the patient selection, to find differences in distribution patterns over discontinuous Percoll density gradients of the eosinophils of asthmatic compared to normal individuals failed to show such a difference. Therefore, the density distribution pattern of eosinophils over these gradients does not reflect cell activation, whereas LTC4 formation clearly does. This could mean that LTC4 formation is a more sensitive parameter for cell activation than density distribution or cell surface marker expression.

Adolescent↗
PubMed1993

A Delphi study of pediatric oncology nurses' facilitative behaviors.

Using a classic Delphi methodology, this study identified the nursing behaviors and interventions that oncology nurses rated as most important in facilitating the patient's, parents', and siblings' coping efforts with the effects of disease and treatment. Random selection of 300 pediatric oncology nurses resulted in a final sample of 69 nurses who completed all 3 rounds of the Delphi. The majority of the nurses were younger than 35 years of age, had less than 10 years of experience, were educated with at least a bachelor's degree, and practiced in an all-oncology setting. Twenty-eight facilitative behaviors were identified for the child with cancer, 25 for the parents, and 25 for the siblings. Results of this study support previous research on patient, parent, and sibling coping.

Adaptation, Psychological↗
PubMed1993

The patello-femoral joint--a critical appraisal of its geometric assessment utilizing conventional axial radiography and computed arthro-tomography.

In the quest for treatable causes of anterior knee pain, plain film skyline views of the patello-femoral joint are requested, often in 30 degrees, 60 degrees and 90 degrees of flexion, to assess the functional relationships of the joint. Patello-femoral malalignment predisposes to recurrent subluxation and dislocation, articular cartilage damage and premature degenerative change. The aim of this study is to evaluate critically, by comparative assessment, the information provided by skyline views and axial computed arthro-tomography (CTA). Measurements of the patello-femoral angle (assesses patellar tilt), the congruence angle (assesses patellar lateralization) and the trochlear depth were made on Merchant's skyline views and on axial CTA on each of 50 symptomatic knees. Results are presented in graphic form with visual examples indicating a poor correlation between the two imaging methods. We conclude that skyline views are inaccurate and unsuitable primarily because they cannot be obtained in less than 30 degrees of flexion. We suggest that skyline views have no role to play in screening for maltracking as even florid examples must be missed, and would strongly urge that no surgery be performed on their basis alone as this would result in inappropriate operations. Although computed tomography is the preferred mode of assessing patello-femoral geometry, difficulties are still encountered and the ways of circumventing them are discussed.

Femur↗
PubMed1993

Potential use of ketoconazole in a dynamic endocrine test to differentiate between biological outliers and testosterone use by athletes.

Determination of the ratio of testosterone to epitestosterone (T/E) in urine is used to detect testosterone administration in athletes, with a ratio > 6 considered as evidence of an offense. We show that administration of ketoconazole, which inhibits testosterone biosynthesis, may be useful for differentiating between an athlete who is using testosterone and one who naturally gives a ratio > 6. In a control subject pretreated with testosterone, ketoconazole caused the ratio to increase; conversely, it caused a decrease in the ratio in an athlete under investigation. Repeated administration of ketoconazole to two normal men caused a decrease in the ratio due to a large decrease in the urinary excretion rate of testosterone relative to epitestosterone. Stimulation with human chorionic gonadotropin exacerbated the differences in excretion rates. A single administration of ketoconazole to six normal men caused the T/E ratios to decrease significantly within 8 h, a suitable time scale for use in a dynamic test.

Adult↗
PubMed1993

Group child health assessments.

'Health for all children' emphasises health promotion and parental involvement in child health surveillance checks. Heavy caseloads and the need to incorporate these principles in their practice prompted an Oxfordshire team of health visitors to introduce group health assessments. Here they describe the new approach and the response from parents.

Child Health Services↗
PubMed1992

p53 mutations in formaldehyde-induced nasal squamous cell carcinomas in rats.

Formaldehyde induces squamous cell carcinomas in the nasal passages of rats following chronic inhalation exposure at concentrations of > or = 10 ppm. We have examined the complementary DNA of the tumor suppressor gene p53 from 11 primary formaldehyde-induced tumors for mutation using DNA sequence analysis. A polymerase chain reaction-amplified fragment of the rat p53 complementary DNA containing the evolutionarily conserved regions II-V was directly sequenced from each tumor. Point mutations in the p53 complementary DNA sequence were found in 5 of 11 of the tumors analyzed. These data demonstrate p53 point mutations in formaldehyde-induced squamous cell carcinomas and indicate a common alteration in certain rat and human squamous cell carcinomas of the respiratory tract.

Animals↗
PubMed1992

Induction and function of eosinophil intercellular adhesion molecule-1 and HLA-DR.

We have previously established that eosinophils studied ex vivo from the sputum of asthmatics express intercellular adhesion molecule-1 (ICAM-1) and HLA-DR, whereas peripheral blood eosinophils do not express these surface proteins. On incubation of highly purified (greater than 99.5% pure) blood eosinophils from normal subjects with T cell supernatants, eosinophil ICAM-1 was induced in 24 h, whereas HLA-DR was maximally induced within 48 h. Recombinant cytokines that enable eosinophil survival (IL-5, IL-3, and granulocyte macrophage-CSF) were found to be unable to induce ICAM-1 or HLA-DR, even when pooled at concentrations individually required for eosinophil survival. However, synergy between these eosinophil survival factors and TNF (-alpha and -beta) was found mainly responsible for ICAM-1 induction, whereas synergy between IL-3 and IFN-gamma occurred for HLA-DR induction. Culture of eosinophils in the presence of cytokines and cycloheximide prevented expression of ICAM-1 and HLA-DR, showing that de novo eosinophil protein synthesis is occurring. At a functional level we demonstrate that ICAM-1-bearing eosinophils have increased adhesion capacity for autologous T cells. In contrast, HLA-DR-expressing eosinophils mediated Ag-specific proliferation of an autologous HLA-DR-restricted T cell clone that was inhibitable by anti-HLA-DR and anti-ICAM-1 mAb. Since eosinophil-mediated Ag presentation was inhibitable by treatment of eosinophils with glutaraldehyde or chloroquine, this suggests that eosinophils participate in Ag uptake, processing, and presentation and have accessory functions. Thus, through the induction of ICAM-1 and HLA-DR on tissue eosinophils, eosinophils have the capacity to interact with leukocytes and present Ag to T cells.

Antigen-Presenting Cells↗
PubMed1992

Cationic lipids direct a viral glycoprotein into the class I major histocompatibility complex antigen-presentation pathway.

Recombinant glycoprotein B (gB) of herpes simplex virus (HSV) was processed and presented by class I major histocompatibility complex (MHC) molecules after delivery into cells by using N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl sulfate (DOTAP), a commercially available cationic lipid used for DNA transfection. Cells treated with DOTAP-associated gB were susceptible to lysis by class I MHC-restricted, HSV-specific cytotoxic T lymphocytes (CTL), and the treated cells restimulated memory gB-specific CTL activity in spleen cells from HSV-infected mice. gB-specific CTL responses were detected in mice immunized with recombinant gB and DOTAP but not in those receiving gB emulsified in complete Freund's adjuvant. Thus, cationic lipids may facilitate induction of CD8+ T-cell responses in vaccinations with recombinant antigens, and they may serve as readily available reagents for dissecting class I MHC immunity to viruses and other intracellular pathogens.

Adjuvants, Immunologic↗
PubMed1992

Predisposition to renal cell carcinoma due to alteration of a cancer susceptibility gene.

A single germ line gene mutation at a tumor susceptibility locus in a rodent model of hereditary human renal cancer caused a 70-fold increase in susceptibility to chemical carcinogenesis. A carcinogen that targeted both renal epithelial and mesenchymal cells caused an increase in tumors of epithelial origin in susceptible animals; the number of carcinogen-induced mesenchymal tumors was unaffected by the presence of the mutation at the susceptibility locus. Thus, this mutation defines a genetic locus for susceptibility to carcinogen-induced tumors and modulation of carcinogen susceptibility by this locus exhibits cell-type specificity.

Animals↗
PubMed1992

The role of T lymphocytes in the pathogenesis of asthma.

Recently there have been advances in our understanding of the role of thymic (T) lymphocytes in asthma. In this brief review we discuss evidence for T cell involvement in asthma, with emphasis on T cell surface markers associated with activation and T cell production of cytokines. We proceed to describe how T cells influence inflammatory effector cells such as mast cells and eosinophils. However, mast cells and eosinophils are also capable of cytokine production, and participate in inflammatory cell networks within the bronchial tissue of asthmatics.

Asthma↗
PubMed1992

Early activation or "priming" of eosinophils in asthma.

Increased numbers of blood and tissue eosinophils are regularly observed in subjects suffering from bronchial asthma. The eosinophil number in the diseased organ is normally closely associated with the presence of clinical symptoms. Not only the cell number, but also the concentration of eosinophil-granule derived mediators is increased in the diseased organ. In particular toxic proteins released by the eosinophil may be responsible for the allergic inflammatory reaction and the concomitant tissue damage. Our recent investigations have shown that eosinophilic granulocytes from asthmatic individuals have the same phenotype as eosinophils from normal individuals (i.e. with respect to their density distribution pattern and surface receptor expression). In contrast, eosinophils from asthmatic individuals do possess increased metabolic activity (i.e. increased leukotriene C4 (LTC4) generating capacity and migration capacity). This increased metabolic activity is due to the presence of circulating factors, i.e. the cytokines interleukin 3 (IL-3), interleukin 5 (IL-5) and granulocyte-macrophage colony stimulating factor (GM-CSF). These cytokines are demonstrable in the circulation of asthmatic, but not normal individuals; they are synthetized by activated T-lymphocytes. This early activation, called "priming", should be the goal of future pharmacological endeavours in order to achieve more efficient treatment of asthma.

Asthma↗
PubMed1992

Characterization of platelet-derived growth factor and platelet-derived growth factor receptor expression in asbestos-induced rat mesothelioma.

Although altered expression of platelet-derived growth factor (PDGF) is a hallmark of human mesothelioma, expression of PDGF receptors has not been characterized in this cell type. In addition, the expression of this growth factor and its cognate receptor in rodent mesothelioma has not been investigated. In this study, examination of transformed mesothelial cells derived from asbestos-induced rat mesotheliomas revealed that these cells expressed high affinity PDGF receptors (Kd = 0.5 nM) and receptor number was 1.6 x 10(5)/cell. Western analysis using antibodies specific for either the alpha-type or beta-type PDGF receptor and Northern analysis using probes specific for alpha- and beta-type receptor RNA transcripts indicated that these cells expressed beta-type PDGF receptors but that alpha-type receptors could not be detected. However, when the mesothelioma-derived cells were examined for the expression of PDGF, no expression of this growth factor could be detected. The transformed cells expressed no detectable A- or B-chain PDGF RNA transcripts; and using a competitive enzyme immunoassay specific for isoforms containing the B chain of PDGF and a sandwich enzyme-linked immunosorbent assay specific for A-chain-containing isoforms, neither AA, nor AB, nor BB isoforms of this growth factor could be detected in medium conditioned by these cells. The absence of alterations in PDGF expression in rat mesothelioma, in contrast to the data for the human disease, suggests that the production of this growth factor by transformed mesothelial cells may be species specific.

Animals↗
PubMed1992

'Fatigue' in patients with multiple sclerosis. Motor pathway conduction and event-related potentials.

Ten patients with a definite diagnosis of multiple sclerosis and complaints of "fatigue" were studied using (1) reaction times and event-related potentials accompanying the performance of auditory memory tasks (target detection, verbal short-term memory) and (2) motor conduction velocities of the pyramidal tract elicited by cerebral and cervical magnetic stimulation. Patients were studied when "rested" and when fatigued. Reaction times of the patients when rested were significantly delayed in the short-term memory but not the target-detection tasks when compared with normal controls. When patients were fatigued, their reaction times became significantly longer in all tasks compared with when they were rested. Event-related potentials in these tasks consist of N1/P2 sensory components and P3a and P3b cognitive components. The N1 component latency was longer and P3a and P3b amplitudes were reduced in patients compared with controls. Fatigue in patients with multiple sclerosis was accompanied by a shortening of P3a latency and an increase in P3a and P3b amplitudes compared with these measures when patients were rested. Pyramidal tract conduction velocities did not differ between rested and fatigued conditions. Thus, fatigue in patients with multiple sclerosis was associated with a slowing of performance (reaction time) on memory tasks, whereas brain potentials reflecting neural events of stimulus encoding and classification were either unchanged or paradoxically speeded up in latency in the fatigued compared with the rested conditions. We postulate that, in patients with multiple sclerosis, fatigue affects neural processes acting after stimulus evaluation but before activation of the primary motor pathways.

Adult↗
PubMed1992

Validation of PTSD measures for older combat veterans.

This study evaluated three nosologically similar older groups (Older PTSD, POW, and Older Psychiatric) and a group of Younger PTSD veterans from Vietnam. Group membership was derived from index admission diagnoses and clinical validation of status. Groups were compared on the MMPI, PTSD measures, background variables, health measures and an outcome measure. Results showed that the Older PTSD group is closer to the Younger PTSD group than to the other groups on the MMPI and PTSD measures and also that members of this group remain in the hospital longer than do members of the other older groups. Parameters of effective test classification showed the PTSD measures to be helpful in correct identification of this disorder for the older groups.

Age Factors↗
PubMed1992

Possible cellular and molecular mechanisms for asbestos carcinogenicity.

Asbestos fibers may exert their carcinogenic effects on mesothelial cells and bronchial epithelial cells by direct and indirect mechanisms. Direct effects can occur following the physical interaction of fibers with target cells or by the generation of free radicals from the fiber surface; indirect effects, following the interaction of fibers with inflammatory cells can result in the production of cellular mediators such as cytokines and various reactive oxygen species. As a result, target cells may be induced to proliferate and/or sustain genetic alterations, which lead to tumor development.

Animals↗