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Biomedical subjects

K D McCoy

Publications and source records attributed to K D McCoy.

17 recordsLinked to original sources
PubMed2003

Spatial genetic structure of the ectoparasite Ixodes uriae within breeding cliffs of its colonial seabird host.

To examine the potential importance of the spatial subdivision of hosts for the functioning of parasite populations, we analysed patterns of local genetic structure within natural populations of the seabird ectoparasite, Ixodes uriae, at the scale of the host breeding cliff. The seabird hosts of this parasite nest in dense colonies with a hierarchical spatial organisation (individual nests-breeding cliffs-colony). Using eight microsatellite markers and samples from three breeding cliffs of the Black-legged kittiwake (Rissa tridactyla), we found that tick populations were indeed genetically structured at this spatial scale. However, the nature of this structuring depended on the characteristics of the cliffs considered. Both the host nest and cliff topography seemed to be important factors in the isolation of tick groups, but their relative roles may depend on the size of the local parasite population. We found no evidence of isolation by distance within a cliff suggesting that independent tick dispersal may not be a significant force influencing population structure in highly infested cliffs. However, genetic structure seemed to decrease with tick life stage, nymphal ticks being more strongly structured than adult ticks. These results may be related to the clustering of tick progeny combined with differential mortality and dispersal probabilities of each life stage. Overall, results indicate that the spatial organisation of hosts can indeed have important consequences for the population genetic structure of their parasites and, thus, may modify parasite dynamics and the scale at which local coevolutionary processes occur.

Animals↗
PubMed2001

Induced maternal response to the Lyme disease spirochaete Borrelia burgdorferi sensu lato in a colonial seabird, the kittiwake Rissa tridactyla.

Mothers are predicted to invest in their offspring depending on the quality of their mate, their opportunity to invest in future reproduction and the characteristics of the habitat in which their offspring will be born. Recent studies have suggested a transfer of maternal immunity to offspring as an induced response to the local presence of parasites in the environment, but evidence has been indirect. Here, we show the presence of antibodies against the Lyme disease agent Borrelia burgdorferi sensu lato, a spirochaete transmitted by the seabird tick Ixodes uriae, in the eggs of kittiwakes Rissa tridactyla. We report higher prevalence of antibodies against Borrelia in eggs from breeding areas with higher prevalence and abundance of ticks. Further, high repeatabilities of antibody-positive eggs within clutches and between first and replacement clutches show that, within a breeding season, females differ consistently with respect to the expression of this induced maternal response. Our results suggest that mothers can alter investment in their young depending on local conditions. Such maternal effects clearly have implications for the ecology and evolution of host-parasite interactions.

Animals↗
PubMed2001

Monitoring adherence to Standard Precautions.

BACKGROUND: Health care workers (HCWs) do not consistently follow Standard Precautions (SP). This is a serious problem because inadequate compliance is associated with increased blood exposure thus predisposing HCWs to bloodborne pathogen transmission. METHODS: The primary goal of this study was to identify institutional factors associated with adequacy of HCW training to monitor coworkers' adherence to SP. Surveys were sent to all community hospital infection control practitioners (ICPs) in Iowa and Virginia. ICPs indicated on a 5-point Likert scale, ranging from strongly disagree to strongly agree, their assessment of HCW training adequacy. Data from another statewide survey of HCWs in Iowa were assessed to validate this outcome measure. Multiple logistic regression models were developed to identify predictors of assessed training adequacy. Independent variables included methods of education, training, approaches to SP compliance assessment, provision of SP reinforcement by clinical leaders, and organizational data. RESULTS: A total of 149 institutions (62%) participated. Models of training program adequacy varied across occupations. Management commitment to SP training programs, leadership support, frequency of providing bloodborne pathogen information, and safety climate were important institutional predictors of assessed adequacy of training. The outcome was validated by demonstrating an association between the ICPs' assessment of HCW training and workers who reported having sufficient information to comply with SP (P <.05). CONCLUSIONS: Institutional safety climate, leadership support, and frequency of education play an important role in HCWs' training adequacy to monitor coworkers' adherence to SP. Occupational groups should be considered independently when strategies are developed to increase compliance. Interventions based on modifiable factors identified by this study may reduce bloodborne pathogen exposure among HCWs.

Blood-Borne Pathogens↗
PubMed2001

Renal actions of the alpha2-adrenoceptor agonist, xylazine, in the anaesthetised rat.

AIMS: The aims of the present study were to characterise the renal effects of the alpha2-adrenergic agonist, xylazine, in the rat and to test the role of changes in glomerular filtration rate, glucosuria, and arginine vasopressin (AVP) in its mechanism of action. METHODS: Male Wistar rats were anaesthetised with pentobarbitone sodium (50 mg/kg), and polyethylene cannulae were surgically placed for blood pressure measurement and for blood and urine collection. Rats were given xylazine and other alpha2 agonists by bolus intravenous dose, and the effects of the drugs were monitored in the presence and absence of the selective alpha2 antagonist, yohimbine, the alpha1, alpha2B antagonist, prazosin, and the V2-receptor antagonist, d(CH2)5 [D-Ile2,Ile4,Ala-NH29]AVP. RESULTS: Xylazine at 2.5 mg/kg caused a significant and prolonged dose-dependent increase in urine flow rate and sodium excretion but had only short-lasting effects on blood pressure, heart rate, and glomerular filtration rate. Prazosin had no effect on the measured responses. Although plasma glucose concentration and glucose excretion rate were increased by xylazine, the magnitudes of these increases were insufficient to account for the diuresis observed. Xylazine, and 2 other alpha2 agonists, clonidine and oxymetazoline, increased urine flow and/or sodium excretion despite the presence of d(CH2)5 [D-Ile2,Ile4,Ala-NH29]AVP. CONCLUSIONS: Xylazine causes a diuretic and natriuretic alpha2A-adrenergic response in the rat that is independent of changes in glomerular filtration rate, the development of glucosuria, or AVP action on the distal nephron of the kidney. CLINICAL RELEVANCE: The adverse effects of xylazine on salt and water balance need to be considered and possibly compensated for by fluid replacement or post-surgical administration of alpha2-receptor antagonists.

Journal Article↗
PubMed2001

Hospital bloodborne pathogens programs: program characteristics and blood and body fluid exposure rates.

OBJECTIVE: To describe hospital practices and policies relating to bloodborne pathogens and current rates of occupational exposure among healthcare workers. PARTICIPANTS AND METHODS: Hospitals in Iowa and Virginia were surveyed in 1996 and 1997 about Standard Precautions training programs and compliance. The primary outcome measures were rates of percutaneous injuries and mucocutaneous exposures. RESULTS: 153 (64%) of 240 hospitals responded. New employee training was offered no more than twice per year by nearly one third. Most (79%-80%) facilities monitored compliance of nurses, housekeepers, and laboratory technicians; physicians rarely were trained or monitored. Implementation of needlestick prevention devices was the most common action taken to decrease sharps injuries. Over one half of hospitals used needleless intravenous systems; larger hospitals used these significantly more often. Protected devices for phlebotomy or intravenous placement were purchased by only one third. Most (89% of large and 80% of small) hospitals met the recommended infection control personnel-to-bed ratio of 1:250. Eleven percent did not have access to postexposure care during all working hours. Percutaneous injury surveillance relied on incident reports (99% of facilities) and employee health records (61%). The annual reported percutaneous injury incidence rate from 106 hospitals was 5.3 injuries per 100 personnel. Compared to single tertiary-referral institution rates determined more than 5 years previously, current injury rates remain elevated in community hospitals. CONCLUSIONS: Healthcare institutions need to commit sufficient resources to Standard Precautions training and monitoring and to infection control programs to meet the needs of all workers, including physicians. Healthcare workers clearly remain at risk for injury. Further effective interventions are needed for employee training, improving adherence, and providing needlestick prevention devices.

Blood-Borne Pathogens↗
PubMed2000

T1-deficient and T1-Fc-transgenic mice develop a normal protective Th2-type immune response following infection with Nippostrongylus brasiliensis.

The IL-1 receptor-related protein T1 is expressed on the surface of Th2, but not Th1 cells. Studies with anti-T1 monoclonal antibodies have suggested that T1 is critical for development of normal Th2-type responses. To elucidate the role of T1 in vivo, we generated T1-deficient mice and a T1-transgenic strain which secretes soluble T1-Fc fusion protein into the serum. These were analyzed for the Th2 immune response induced by infection with the parasitic nematode Nippostrongylus brasiliensis. Although Th2 cytokine production by lymph node cells was similar in all groups of N. brasiliensis-infected mice, a decrease in IL-5 production by lung lymphocytes was detected in both T1-deficient and T1-Fc-transgenic mice compared to control littermates. This difference in IL-5 production did not influence blood eosinophilia, but recruitment of eosinophils into lung tissue, especially in T1-Fc-transgenic mice was slightly decreased. However, induction of all other immune parameters was normal and both T1-deficient and T1-Fc-transgenic mice were able to clear the parasite infection within 12 days with kinetics similar to those in control mice. Therefore, in contrast to previous suggestions, we conclude that the T1 protein is not obligatory for normal development of Th2 immune responses.

Animals↗
PubMed1999

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) can regulate dendritic cell-induced activation and cytotoxicity of CD8(+) T cells independently of CD4(+) T cell help.

The mechanisms that regulate the strength and duration of CD8(+) cytotoxic T cell activity determine the effectiveness of an antitumor immune response. To better understand the antitumor effects of anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody treatment, we analyzed the effect of CTLA-4 signaling on CD8(+) T cells in vitro and in vivo. In vitro, cross-linking of CTLA-4 on purified CD8(+) T cells caused decreased proliferative responses to anti-CD3 stimulation and rapid loss of activation marker expression. In vivo, blockade of CTLA-4 by neutralizing anti-CTLA-4 mAb greatly enhanced the accumulation, activation, and cytotoxic activity of CD8(+) T cells induced by immunization with Ag on dendritic cells (DC). This enhanced response did not require the expression of MHC class II molecules on DC or the presence of CD4(+) T cells. These results demonstrate that CTLA-4 blockade is able to directly enhance the proliferation and activation of specific CD8(+) T cells, indicating its potential for tumor immunotherapy even in situations in which CD4(+) T cell help is limited or absent.

Abatacept↗
PubMed1999

CTLA4 ligation attenuates AP-1, NFAT and NF-kappaB activity in activated T cells.

CTLA4 is currently viewed as a late-appearing T cell surface receptor which is able to inhibit the proliferation of activated T cells. We sought to identify how CTLA4 ligation exerts these anti-proliferative effects by studying its influence on the activities of the relevant nuclear transcription factors AP-1, NFAT and NF-kappaB. We found that cross-linking CTLA4 on activated T cells completely blocks AP-1 and NFAT transcription factor activity before any effects on T cell proliferation can be observed, with NF-kappaB activity affected to a lesser degree. The suppression of AP-1 and NFAT transcriptional activity correlates with reduced levels of AP-1 and NFAT DNA binding as early as 10 h after T cell activation, prior to detectable up-regulation of CTLA4 on the T cell surface. Additionally, inhibitory effects on T cell proliferation only occurred when CTLA4 molecules were ligated in proximity to signaling TCR complexes, and inhibition of transcription factor DNA binding and activity was observed in the absence of CD28 stimulation. CTLA4 can thus act early during T cell activation to reduce the activity of several key nuclear transcription factors important for continued T cell proliferation and differentiation.

Abatacept↗
PubMed1999

The role of CTLA-4 in the regulation of T cell immune responses.

Over the past few years a great deal of research has examined how T cell-dependent immune responses are initiated and subsequently regulated. Ligation of the TCR with an antigenic peptide bound to an MHC protein on a professional APC provides the crucial antigen-specific stimulus required for T cell activation. Interaction of CD28 with CD80 or CD86 molecules on APC initiates a costimulatory or second signal within the T cell which augments and sustains T cell activation initiated through the TCR. However, recently it has become clear that T cell immune responses are a result of a balance between stimulatory and inhibitory signals. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) is a cell surface molecule that is expressed nearly exclusively on CD4+ and CD8+ T cells. Investigation into the role of CTLA-4 in the regulation of T cell immune responses has revealed that CTLA-4 is a very important molecule involved in the maintenance of T cell homeostasis. In the present review, evidence for the proposed inhibitory role of CTLA-4 is examined and a model suggesting a role for CTLA-4 in both early and late stages of T cell activation is presented.

Abatacept↗
PubMed1999

Linked insurance-tumor registry database for health services research.

OBJECTIVE: Breast cancer screening and treatment data are often limited to restricted populations, including women older than 65 years old. The goal of this project was to develop procedures to link tumor registry and insurance claims databases on women younger than 65 years old with breast cancer and to assess the accuracy and validity of the linked dataset. METHODS: Iowa Cancer Registry (ICR) and Wellmark Blue Cross/Blue Shield of Iowa (BC/BS) membership files of women with incident in situ or invasive breast cancer from 1989 to 1996 were linked. An automated deterministic match was followed with visual inspection from three independent reviewers applying a matching protocol. Matched and overall registry data were compared to assess population representativeness. Claims from BC/BS for incident cases during 1994 were examined for coding of a recent breast cancer diagnosis or treatment. RESULTS: The final dataset included 4,397 matched cases of patients aged 21 years and older from 1989 to 1996. The sociodemographic and tumor characteristics of the ICR population younger than 65 years old (n = 7,469) with breast cancer or carcinoma in situ were nearly identical with those of the matched patients younger than 65 years old (n = 3,449). Nearly all (96%) of the 445 matched incident cases in 1994 had claims data (CPT, DRG, or ICD-9 code) indicative of breast cancer. Treatment patterns varied by data source, with agreement ranging from 76% to 82%. CONCLUSIONS: The validity and generalizability of these data demonstrate their potential for further health services research among younger insured women with breast cancer. Additionally, the process outlined may be useful for developing other datasets to study other cancers in the population younger than 65 years old.

Adult↗
PubMed1999

Dispersal and distribution of the tick Ixodes uriae within and among seabird host populations: the need for a population genetic approach.

The aim of this study was to characterize the spatial distribution of the tick Ixodes uriae within and among populations of its seabird hosts and to consider the potential insight that could be gained by a population genetic approach to the issue of dispersal of this tick. Analyses of data collected around the Avalon Peninsula, Newfoundland, indicated that both the prevalence and mean abundance of ticks varied significantly among sample locations. Whereas ticks were found on all 4 host species examined (Rissa tridactyla, Uria aalge, Alca torda, Fratercula arctica), infestation prevalence and mean abundance differed among the species. On R. tridactyla, ticks were significantly aggregated at the among-nest scale and nestling infestation was spatially autocorrelated. Conversely, ticks were not aggregated among chicks within nests. These results enabled us to make a priori predictions regarding tick dispersal and host specificity and suggest there may be spatial structure of Ixodes uriae populations at both macro- and microgeographic scales. Investigating the population genetic structure of ticks within and among populations of hosts with different breeding biologies should provide direct insight into the metapopulation dynamics of such a spatially structured system.

Animals↗
PubMed1998

Discriminant function analysis of malingerers' and neurological headache patients' self-reports of neuropsychological symptoms.

Interpretation of a patient's neuropsychological examination involves the determination of the role motivational and psychiatric factors may have played. The ability to detect malingering becomes crucial, particularly when the examination occurs as a result of litigation. Moreover, falsely identifying a performance as distorted has serious consequences for the patient. The present study was conducted to replicate previous research that discriminated between malingered and nonmalingered responses to a neuropsychological self-report inventory. An overall hit rate of 84% for malingerers and neurologic headache patients demonstrated replication of the inventory's ability to identify malingerers. Of those predicted to be malingerers, 27% were false positives indicating the need to use this inventory in conjunction with other neuropsychological measures.

Journal Article↗
PubMed1997

The hemopoietic growth factor, interleukin-3, promotes glucose transport by increasing the specific activity and maintaining the affinity for glucose of plasma membrane glucose transporters.

Most mammalian cells rely on an external supply of glucose for survival, proliferation, and function. Glucose enters cells through specific transporter molecules at the plasma membrane by a facilitative process that does not expend energy. Regulation of glucose transport into cells is thought to occur largely through transporter expression at the cell surface, but the extent to which the intrinsic properties of glucose transporters are regulated is at present controversial. Using a bone marrow-derived cell line that responds to the hemopoietic growth factor, interleukin-3 (IL-3), we investigated IL-3 regulation of glucose transport. IL-3 significantly increased 2-deoxyglucose (2-DOG) uptake within 1 h (26 +/- 8.0%, n = 11) with a maximum 73% increase after 6 h. Withdrawal of IL-3 resulted in decreased uptake within 1 h and this continued to decline to 43% of initial uptake by 16 h. To determine whether these changes in 2-DOG uptake were associated with corresponding changes in glucose transporter expression, subtype-specific antisera against Glut-1 and Glut-3 were used. Little change in membrane expression of these transporters was observed prior to 16 h. Fractionation of cell membranes on Nycodenz gradients showed that the majority of each transporter subtype was associated with the plasma membrane (63-93%) and that transporter distribution did not change markedly in response to addition or withdrawal of IL-3. These results demonstrate that IL-3 regulates glucose uptake by modulating the intrinsic transporting ability of glucose transporters. Decreased transporter affinity for 2-DOG and 3-O-methylglucose was observed following IL-3 withdrawal. Similar affinity changes were observed with 2-DOG following exposure of IL-3-stimulated cells to the protein kinase inhibitors, genistein and staurosporine. In contrast, the tyrosine phosphatase inhibitor, vanadate, acted like IL-3 to increase transporter affinity for glucose. Together these results demonstrate that IL-3 acts to maintain the intrinsic transport properties of glucose transporters without markedly affecting their expression or translocation.

3-O-Methylglucose↗
PubMed1996

CD95 (Fas/Apo-1)-induced apoptosis results in loss of glucose transporter function.

Treatment of activated human T cells with CD95 (Fas/Apo-1) ligand or Abs against CD95 results in apoptotic cell death. Although cellular responses to CD95 ligation have been described in some detail, the early molecular events that result in T cell death are only now beginning to be elucidated. Using Jurkat cells as a model of activated human T cells, we have investigated the effects of CD95 ligation on glucose transport and on glucose transporter function. We show that within minutes of CD95 activation, the ability to transport glucose across the plasma membrane is compromised and that transient exposure to Abs against CD95 for as little as 3 min results in reduced glucose transport and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) responses measured at 16 h. The effects of CD95 ligation on glucose transport are shown to be associated with loss of affinity of glucose transporters for glucose without altered maximum velocity and without changes in the cell surface expression of Glut 1, the predominant glucose transporter isotype on Jurkat cells. These results support a model of CD95 induced cell death that, at least in its early stages, does not depend on signaling to the nucleus or on macromolecular synthesis. Acute regulation of glucose transport is proposed to be an early effector mechanism in CD95-induced apoptotic cell death.

Antibodies, Monoclonal↗
PubMed1996

An exploratory stepwise discriminant function analysis of malingered and nondistorted responses to the Neuropsychological Symptom Inventory.

Clinicians are often asked to evaluate a patient's potential for malingering during a neuropsychological examination. This problem is particularly crucial when financial gain may hinge on the results of the assessment. Response distortion may occur even when a head injury has been verified by radiological means (e.g., MRI). Research in the identification of malingering has yet to produce results that are effective in the clinical setting. The present study addressed several shortcomings of past research with the use of a self-report symptom inventory. The responses of 242 subjects told to distort symptomology were compared to 128 nonmalingerers. A discriminant function analysis of these data produced a 90% hit rate overall with 2.3% false positives. The results were discussed in terms of clinical utility.

Cognition Disorders↗