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Biomedical subjects

L Gardner

Publications and source records attributed to L Gardner.

At least 19 recordsLinked to original sources
PubMed2005

Sex change strategy and the aromatase genes.

Sequential hermaphroditism is a common reproductive strategy in many teleosts. Steroid production is known to mediate both the natural and induced sex change, yet beyond this the physiology directing this process has received little attention. Cytochrome P450 aromatase is a key enzyme in the hormonal pathway catalysing the conversion of sex steroids, androgens to oestrogens, and thus is highly relevant to the process of sex change. This study reports the isolation of cDNA sequences for aromatase isoforms CYP19A1 and CYP19A2 from teleost species representing three forms of sexual hermaphroditism: Lates calcarifer (protandry), Cromileptes altivelis (protogyny), and Gobiodon histrio (bi-directional). Deduced amino acid analysis of these isoforms with other reported isoforms from gonochoristic (single sex) teleosts revealed 56-95% identity within the same isoform while only 48-65% identity between isoforms irrespective of species and sexual strategy. Phylogenetic analysis supported this result separating sequences into isoform exclusive clades in spite of species apparent evolutionary distance. Furthermore, this study isolates 5' flanking regions of all above genes and describes putative cis-acting elements therein. Elements identified include steroidogenic factor 1 binding site (SF-1), oestrogen response element (ERE), progesterone response element (PRE), androgen response element (ARE), glucocorticoid response elements (GRE), peroxisome proliferator-activated receptor alpha/retinoid X receptor alpha heterodimer responsive element (PPARalpha/RXRalpha), nuclear factor kappabeta (NF-kappabeta), SOX 5, SOX 9, and Wilms tumor suppressor (WTI). A hypothetical in vivo model was constructed for both isoforms highlighting potential roles of these putative cis-acting elements with reference to normal function and sexual hermaphroditism.

Animals↗
PubMed2005

LARALink: a web application for cytogenetic linkage analysis.

Genomic and expression data have increased dramatically over the last several years. This is primarily due to the completion of the human genome project as well as an upsurge in the use of various high-throughput technologies. Recent attempts to correlate genomic and expression data have stimulated the scientific community to determine how this data can be used within a clinical setting (P Khatri et al., Genomics 2002: 79: 266; LJ van't Veer et al., Nature 2002: 415: 530). LARALink (Loci Analysis for Rearrangements Link) is a database-driven web application that utilizes several public datasets to analyze clinical cytogenetic data to identify candidate genes. LARALink allows UniGene clusters or single-nucleotide polymorphisms (SNPs) to be queried for multiple patients by cytoband, chromosome marker, or base pair. The results can be further refined with the use of an anatomical site, developmental stage, pathology, or cell-type expression filter. Once a set of UniGene clusters (expressed genes) has been identified either for a single patient or for a shared region among multiple patients, the expression-distribution profile, expressed sequence tags (ESTs), or online mendelian inheritance in man (OMIM) entries are displayed. The utility of this tool is shown by its application to both research and clinical medicine. LARALink is a public resource available at: http://www.laralink.bioinformatics.wayne.edu:8080/unigene.

Alzheimer Disease↗
PubMed2004

Provider barriers to prescribing HAART to medically-eligible HIV-infected drug users.

We aimed to identify factors associated with a medical provider's resistance to prescribing HAART to medically-eligible HIV-infected illicit drug users. In four US cities, a mailed, self-administered survey queried 420 HIV care providers about patients' characteristics and barriers to care. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were estimated using logistic regression. Providers identified as resistant to prescribing HAART to medically-eligible HIV-infected illicit drug users were more likely to be non-physicians (AOR=1.89, 95% CI: 1.04-3.46), to work in populations with a high prevalence of both mental illness (AOR=2.42; 95% CI: 1.11-5.26) and injection drug use (AOR=1.82 95% CI: 1.02-3.25) and were deterred from prescribing HAART by patients' limited ability to keep appointments, (AOR=3.19; 95% CI: 1.39-7.37), alcoholism (AOR=1.92; 95% CI: 1.04-3.55) and homelessness (AOR=1.81; 95% CI: 1.07-3.06). Providers working in populations with a high injection drug use prevalence commonly reported higher prevalence of non-injection drug use, alcohol problems and mental illness, and higher antiretroviral therapy refusal rates within their patient populations. Our findings underscore the challenges to providers who treat HIV-infected drug users and suggest that their care and treatment would benefit from on-site drug treatment, mental health and social services.

Antiretroviral Therapy, Highly Active↗
PubMed2001

HLA-G expression by tumors.

PROBLEM: It has been proposed that the expression of the non-classical MHC class I antigen, HLA-G, by trophoblast is one mechanism by which the placenta evades attack by maternal uterine NK cells. A similar mechanism is thought to be operative in the escape from immunosurveillance by tumor cells. However, data on the expression of HLA-G by tumor cells are highly conflicting. METHOD OF STUDY: In the present study, we have examined tissue sections from a wide variety of tumors by immunohistology and also several cell lines by flow cytometry and RT-PCR. Whilst very faint bands were detected in three cell lines (hepG2, Mead, CaSki) by RT-PCR, no tumors or cell lines were observed to express HLA-G protein. Furthermore, we found that tumor deposits are not usually infiltrated by NK cells. CONCLUSION: Our observations, therefore, do not support the proposal that tumor cells express HLA-G in order to evade host NK cell cytolysis.

HLA Antigens↗
PubMed2001

Angiogenic growth factor messenger ribonucleic acids in uterine natural killer cells.

Angiogenesis is essential for endometrial growth and repair, and disruption of this process may lead to common disorders of women, including menorrhagia and endometriosis. In pregnancy, failure of the endometrial spiral arterioles to undergo remodeling leads to preeclampsia. Here we report that in addition to vascular endothelial growth factor A (VEGF-A), human endometrium expresses messenger ribonucleic acids (mRNAs) encoding VEGF-C, placenta growth factor (PlGF), the angiopoietins, angiopoietin 1 (Ang1) and Ang2, and the receptors VEGFR-3 (Flt-4), Tie 1, and Tie 2. Levels of VEGF-C, PlGF, and Tie 2 changed during the menstrual cycle. Intense hybridization for VEGF-C and PlGF mRNAs was found in uterine nature killer cells in secretory phase endometrium and for Ang2 mRNA in the same cells in the late secretory phase. Interleukin-2 (IL-2) and IL-15 up-regulated VEGF-C, but not PlGF or Ang2, mRNA levels in isolated NK cells. Conditioned medium from decidual NK cells did not induce human umbilical vein endothelial cell apoptosis. These results indicate that human endometrium expresses a wide range of angiogenic growth factors and that uterine nature killer cells may play an important role in the abnormal endometrial angiogenesis that underlies a range of disorders affecting women.

Angiogenesis Inducing Agents↗
PubMed2000

Occupational injuries in the mining industry and their association with statewide cold ambient temperatures in the USA.

BACKGROUND: Relatively few occupational epidemiological studies have been conducted concerning the association between cold ambient temperatures and cold exposure injuries, and fewer still of traumatic occupational injuries and cold ambient temperatures. METHODS: The association of ambient temperature and wind data from the National Climatic Data Center with injury data from mines reported to the Mine Safety and Health Administration (MSHA) was evaluated over a 6 year period from 1985-1990; 72,716 injuries from the seven states with the most numerous injuries were included. Temperature and wind data from each state's metropolitan weather stations were averaged for each day of the 6 year period. A weighted linear regression tested the relationship of ungrouped daily temperature and injury rate for all injury classes. For cold exposure injuries and fall injuries, relative incidence rates for grouped temperature data were fit with Poisson regression. RESULTS: As temperatures decreased, injury rates increased for both cold exposure injuries and slip and fall injuries. The association of slip and fall injuries with temperature was inverse but not strictly linear. The strongest association appeared with temperatures 29 degrees F and below. The injury rates for other accident categories increased with increasing ambient temperatures. CONCLUSIONS: This study suggests that statewide average ambient temperature reflects the expected association between the thermal environment and cold exposure injuries for workers, but more importantly, documents an association between ambient temperatures and occupational slip and fall injuries.

Accidental Falls↗
PubMed2000

Surface expression of HLA-C antigen by human extravillous trophoblast.

In this paper definitive evidence that the classical class I product, HLA-C, is expressed on the surface of normal trophoblast cells is provided. HLA-C transcripts were sequenced from cDNA isolated from first trimester trophoblast cells obtained by flow cytometric sorting. Both paternal and maternal alleles were transcribed. HLA-C proteins were demonstrated by biochemical analysis and found on the cell surface in association with beta(2)-microglobulin. Upregulation of cell surface HLA-C but not HLA-G expression after interferon (IFN)-gamma treatment was demonstrated by flow cytometric analysis. Immunohistology has confirmed HLA-C is expressed by all extravillous subpopulations in vivo. The question of whether trophoblast HLA-C molecules interact with decidual NK cells expressing killer Ig-like receptors (KIR) has also been addressed. Our results demonstrate that extravillous trophoblast expresses at least two HLA class I molecules, HLA-G and HLA-C on the cell surface.

Adult↗
PubMed1999

Developing the role of the generic healthcare support worker: phase 1 of an action research study.

This paper reports on the first phase of an action research practice development project to explore, develop and evaluate the role of the generic healthcare support worker in a high dependency rehabilitation service. The project is being jointly conducted by staff from the University of Southampton, the University of Portsmouth and the Isle of Wight Healthcare NHS Trust and phase 1 is supported by a grant from the NHS Executive (South and West). The aim of phase 1 of the project is to explore the attitudes of staff towards the implementation of the role of the generic healthcare support worker, particularly regarding the practical, professional and ethico-legal problems of the role. Professional and support staff from different parts of the service were interviewed in groups and the interviews were tape recorded, transcribed and subjected to a simple thematic analysis. Four themes emerged from the data relating to the challenge to professional boundaries, being a generic worker, outcomes for service and patients and implementing the role. As an action research project, the aim was not to produce findings that are generalizable beyond the practice areas in which they were generated, but it is nevertheless hoped that the reader might be able to apply some of the conclusions to his or her own setting.

Attitude of Health Personnel↗
PubMed1999

Co-stimulation of human decidual natural killer cells by interleukin-2 and stromal cells.

At the late secretory phase of the menstrual cycle and in early pregnancy, the uterine mucosa is infiltrated by large numbers of natural killer (NK) cells with a distinctive phenotype (CD56bright CD16- CD3-) and large granular lymphocyte (LGL) morphology. Circulating CD56bright NK cells generally proliferate in the presence of interleukin-2 (IL-2), but it is clear that cofactors besides IL-2 are required for optimal response. In the bone marrow, this co-stimulating signal is provided by stromal cells. In the present study we observe that uterine CD56+ cells from early pregnancy decidua similarly proliferate vigorously when cultured with decidual stromal cells and a suboptimal dose of IL-2. This response is dependent on cell-cell contact, as no proliferation of decidual NK cells was observed when they were separated from stromal cells by a permeable cyclopore membrane. In addition, we have studied the expression of Bcl-2 by decidual CD56+ cells. Our results show that the microenvironment of the uterus is likely to have a significant influence on the proliferation and survival of uterine CD56+ cells.

CD3 Complex↗
PubMed1999

The role of trophoblast in the physiological change in decidual spiral arteries.

The remodelling of the maternal uterine spiral arteries during pregnancy, known as physiological change, is critical for the normal growth and development of the fetus. Controversy has surrounded the part played by fetal trophoblast in the transformation of these spiral arteries. To address this debate, a histological and immunochemical comparison of blood vessels from the implantation sites of human pregnancies of early gestation with uterine tissue where trophoblast was absent was performed. Results showed that true physiological change, with the features of medial necrosis and deposition of fibrinoid material, only occurred in the presence of trophoblast. In addition, it was found that subpopulations of trophoblast contribute differently in the process. Interstitial trophoblast-mediated destruction of the arterial media precedes replacement of the endothelial cells by endovascular trophoblast.

Arteries↗
PubMed1998

Expression of CD3 epsilon, CD3 zeta, and RAG-1/RAG-2 in decidual CD56+ NK cells.

In early pregnancy the uterine mucosa, the decidua, is infiltrated by numerous CD56bright, CD16- natural killer (NK) cells. In this paper we have shown that unlike adult peripheral blood NK cells these uterine NK cells express cytoplasmic CD3 and CD3 zeta, but CD3 gamma and CD3 delta were not found in the majority of cells. In contrast to previous reports, there was no evidence of RAG-1 nor RAG-2 expression in decidual NK cells. These findings have implications for the ontogeny and development of decidual NK cells.

CD3 Complex↗
PubMed1998

QT prolongation and dispersion in myocardial ischemia and infarction.

The ability of QT interval dispersion to predict the occurrence of ventricular fibrillation (VF) after acute myocardial infarction treated with thrombolytic therapy is controversial. Continuous 12-lead electrocardiographic (ECG) monitoring for 48 hours or longer provides an opportunity to detect transient changes of QT dispersion and correlate such changes with the clinical outcome. In 543 consecutive patients enrolled in the TAMI-9 and GUSTO I studies, serial changes of the QT dispersion were analyzed in an attempt to predict the occurrence of VF with a system that monitored continuously the 12-lead ECG and stored it at least every 20 minutes. Measurements of QT dispersion were made at a median time of 2.37 hours after the onset of chest pain and at 24- and 48-hour intervals. A total of 43 patients experienced VF during the acute phase of myocardial infarction; of these patients, 33 (77%) had anterior infarcts. However, despite the higher preponderance of anterior myocardial infarcts in the VF group, patients with anterior infarcts did not have longer QT dispersion than those with other infarct locations. Similarly, no significant differences in the QT dispersion were observed at any time between the group with VF and that without. Women had increased QT dispersion in the initial and 24-hour ECG as compared with men (P = .005). However, this normalized at the 48-hour measurements. Despite this difference, there was no higher incidence of VF in female patients. In conclusion, the data suggest that QT dispersion alone is not sufficient to explain the occurrence of VF in the acute phase of myocardial infarction after thrombolytic therapy.

Electrocardiography↗
PubMed1998

Consensus guidelines for the promotion and management of continence by primary health care teams: development, implementation and evaluation. NHS Executive Nursing Directorate.

A project was undertaken as part of the NHS Executive Strategy for Major Clinical Guidelines, involving the development of national clinical guidelines for the promotion and management of continence by primary health care teams, through the process of managed consensus based on scientific review. The guidelines were then implemented at one urban general practice. This article outlines the development and implementation of the guidelines and describes the study undertaken to evaluate the impact of implementation on clinical outcomes. The study involved a pre-and post-implementation postal survey of a random sample of 17% of patients aged 18 years and over from the practice (n = 1503). The pre-implementation survey determined the period prevalence of incontinence, related biological data and data on the pre-implementation management of incontinence. Incontinence sufferers were invited to have their condition assessed or reviewed. All sufferers who agreed to be followed-up were sent the post-implementation survey, which identified those patients who had sought help, and ascertained reasons for not seeking help. Data on the management of incontinence post-implementation were also obtained. Clinical outcomes measured pre- and post-implementation were a validated severity index for urinary incontinence, (also adapted for faecal incontinence) and perception of the incontinence as a problem. A 3-month period was allowed between pre- and post-implementation surveys. The study confirmed previous research which showed that few incontinence sufferers respond to invitations to seek help, and that help-seeking behaviour was significantly related to severity of incontinence. The guidelines did not have any positive impact on the clinical outcomes measured, although slight improvements in approaches taken by the primary health care team to the promotion and management of continence were recorded. However, the study was limited by the small sample size and short time scale. Further evaluation of the impact of the guidelines on these outcomes is therefore recommended.

Female↗
PubMed1997

A new classification and diagnostic criteria for invasive fungal sinusitis.

OBJECTIVE: To develop criteria for the diagnosis of invasive fungal sinusitis. DESIGN: Review of the literature on invasive fungal sinusitis in the context of a population of 30 patients with fungal sinusitis and 24 patients with chronic bacterial sinusitis. SETTING: Tertiary care medical center. RESULTS: Our review revealed no consensus in the literature on the classification of the syndromes of invasive fungal sinusitis and no criteria for their diagnosis. Moreover, the existing syndromes of invasive fungal sinusitis lacked specificity and one of the more commonly cited syndromes, primary aspergillosis of the paranasal sinuses, is a granulomatous disease that occurs rarely outside Africa. Two of our 30 patients with fungal sinusitis had a previously unrecognized form of invasive disease. Both were middle-aged adults with well-controlled type 2 diabetes mellitus, apical orbital syndrome, and a similar course: proptosis resulting from fungal expansion out of an ethmoid sinus, a protracted illness of 6 months or longer, visual changes, late neurological symptoms reflecting cavernous sinus invasion, and death. The syndrome in these 2 patients is distinct from the syndrome of fulminant invasive fungal sinusitis, (eg, mucormycosis) with nasal eschar, intracerebral fungal dissemination by vascular invasion, and death in days, and the granulomatous form. CONCLUSIONS: We conclude that there are 3 forms of invasive fungal sinusitis and propose that they be termed (1) granulomatous, (2) acute fulminant, and (3) chronic invasive. The latter category reflects the syndrome seen in our 2 patients. Furthermore, the following 2 diagnostic criteria for invasive fungal sinusitis are proposed: (1) sinusitis confirmed by radiological imaging and (2) histopathological evidence of hyphal forms within sinus mucosa, submucosa, blood vessels, or bone. The specificity of hyphae within sinus mucosa for tissue invasion was supported by the absence of stainable hyphae in the mucosa of patients with chronic bacterial sinusitis or in the mucosa of our described patients with allergic fungal sinusitis and mycetoma.

Adult↗
PubMed1997

Design factors in epidemiologic cohort studies of work-related low back injury or pain.

The connection between work-related exposures and the onset of back injury or pain is complex and not clearly understood. This paper raises design issues related to the planning and conduct of cohort studies of industrial low back pain (or injury)(LBP), with care given to definition and measurement of exposure and outcome events. These issues include sample size, outcome definition, study biases, and practical considerations when seeking and maintaining company collaboration with a research effort. Without resolving these issues, the authors conclude: (1) cohort studies of worksite-based LBP are needed to elucidate the causal associations between work tasks and LBP onset, (2) both acute and cumulative exposures should be assessed as risk factors for low back injury or pain, and (3) attention should be paid to the planning of such studies and minimization of potential biases that can limit the validity of the results. These design issues will benefit researchers and companies engaged in the planning and conduct of cohort studies of industrial LBP.

Accidents, Occupational↗
PubMed1997

Evaluation of trophoblast HLA-G antigen with a specific monoclonal antibody.

A monoclonal antibody to HLA-G has been generated by immunizing HLA-A2.1/human beta 2-microglobulin (beta 2 m) double transgenic mice with murine L cells transfected with both human beta 2 m and HLA-G. This monoclonal antibody, designated as G233, has been found not to cross-react with other HLA class I antigens when tested on numerous cell lines by flow cytometry. With immunohistology, all populations of extravillous trophoblast (cell columns, interstitial trophoblast, endovascular trophoblast, placental bed giant cells) were stained. An extensive range of adult and fetal tissues was also tested but none reacted with monoclonal antibody G233, including those previously reported to express HLA-G mRNA, indicating that the protein has a highly restricted distribution. Failure to detect HLA-G in the fetal thymus raises the question as to how T-cell tolerance to this antigen is induced. Immunoprecipitation of trophoblast surface proteins with monoclonal antibody G233 revealed a heavy chain of 39 kDa and a light chain of 12 kDa, indicating that HLA-G expressed on the surface of trophoblast is complexed with beta 2 m. However, sequential immunoprecipitation with monoclonal antibody W6/32 followed by monoclonal antibody G233 continued to detect a residual band of 39 kDa, suggesting that trophoblast surface HLA-G may also occur as free heavy chains not associated with beta 2 m. Immunoprecipitation followed by two dimensional gel electrophoresis showed that monoclonal antibody G233 recognizes several isoforms of HLA-G from trophoblast similar to the characteristic spot array previously described for HLA-G. This monoclonal antibody G233 will be highly useful in future experiments to elucidate the function of HLA-G.

Adult↗
PubMed1997

Uterine NK cells and trophoblast HLA class I molecules.

PROBLEM: To investigate the proposal that NK cells in decidua may control trophoblast migration during implantation of the human placenta. METHOD: Use Mab specific for HLA-G and for HLA-C in association with flow cytometry and immunoprecipitation to determine the expression of these HLA molecules by trophoblast. Expression of Killer inhibitory/activatory receptors (KIR/KAR) and the CD94 receptor by decidual NK cells was also studied. RESULTS: Extravillous trophoblast expressed HLA-G and HLA-C in both beta2m-associated form and as free heavy chains. KIR and KAR are expressed by decidual NK cells. The repertoire of receptors varied between different women and also between blood and decidual NK cells from the same women. The expression of CD94 was also different between blood and decidual NK cells. CONCLUSION: The recognition of HLA-G/HLA-C by KIR/KAR and CD94 could provide a mechanism by which decidual NK cells control trophoblast migration.

Antibodies, Monoclonal↗