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Biomedical subjects

G Anderson

Publications and source records attributed to G Anderson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Studies on the role of IL-7 presentation by mesenchymal fibroblasts during early thymocyte development.

T cell precursor development depends upon poorly defined interactions between thymocyte precursors and stromal cells involving cell surface molecules, extracellular matrix (ECM) components and soluble growth factors. To determine whether presentation of soluble factors by ECM is involved in early T cell development, we analyzed expression of ECM components in individual thymic stromal subsets and investigated their ability to present ECM-associated IL-7, a factor known to be important during early thymocyte development. We show that MHC class II(+) thymic epithelium and fibroblasts - essential requirements for development of CD4(-)8(-)precursors - both show surface expression of ECM components such as fibronectin and heparan sulfate. Use of biotinylated IL-7 protein indicates that both cell types bind IL-7, while enzymatic disruption of specific ECM components indicates that IL-7 presentation by both cell types is dependent upon heparan sulfate. However, disruption of IL-7 presentation specifically on fibroblasts does not affect their ability to contribute to T cell development. Collectively, these data suggest that while ECM-mediated presentation of IL-7 may be a general function of thymic stromal cells during thymocyte development, heparan sulfate-mediated IL-7 presentation specifically by fibroblasts is not essential and that the specific requirement for fibroblasts in early development involves additional undefined interactions.

Animals↗
PubMed2000

RNA and protein expression of the murine autoimmune regulator gene (Aire) in normal, RelB-deficient and in NOD mouse.

Mutations in the putative transcription factor autoimmune regulator (AIRE) gene are responsible for autoimmune polyendocrinopathy-candidiosis-ectodermal dystrophy (APECED; OMIM#240300), a monogenic recessively inherited disease characterized by destructive autoimmune diseases of the endocrine organs, chronic candidiosis of mucous membranes and ectodermal dystrophies. In this study the expression of murine homolog for AIRE protein, Aire, was detected in a fraction of thymic medullary epithelial cells. Subcellularly, in thymus the protein appears as concentrated into nuclear dot-like structures, whereas in transfected cells the protein is also bound along a cytosolic fibrillar network. By RT-PCR Aire mRNA was detected in thymus, lymph node, spleen and testis although the second round PCR amplified Aire specific band from most mouse tissues analyzed. Furthermore, the Aire mRNA was detected in dendritic cell (DC) populations isolated from thymus and spleen, representing both myeloid- and lymphoid-related lineages of DC. We also demonstrate that the Aire protein is absent in the thymus of RelB-deficient mouse and in NOD thymus most of the Aire positive cells showed an abnormal morphology. These results suggest that the Aire protein is associated with the normal development and/or action of a subset of thymic medullary stromal cells involved in tolerance induction.

Alternative Splicing↗
PubMed2000

Reply.

Explore the source record for details and available documents.

Editorial↗
PubMed2000

Microenvironmental regulation of T cell development in the thymus.

T cell development in the thymus occurs through a series of events beginning with thymic colonization by migrant precursors and ending with the emigration of functionally competent CD4+ and CD8+ T cells to the periphery. It is well accepted that signals through the pre-T cell receptor (pre-TCR) and alpha-beta TCR (alphabetaTCR) complex play pivotal roles in the maturation of CD4-8- and CD4+8+ thymocytes, respectively. It is clear that stromal cells constituting the thymic microenvironment provide non-TCR-mediated interactions which are essential for several developmental events. Examples of such will be discussed here in relation to early and late events in T cell development.

Cell Differentiation↗
PubMed2000

Reported ovarian cancer screening among a population-based sample in Washington state.

OBJECTIVE: To assess the prevalence of reported ovarian cancer screening among a population-based sample of women from Washington state and identify factors that influence the decision to be screened. METHODS: A population-based sample of 6749 women aged 54-84 years, living in 40 predominately rural communities in Washington state, was surveyed about their utilization of ultrasonography and CA 125 for ovarian cancer screening. We also assessed relevant demographic, family history, psychosocial, and health behavior variables. RESULTS: After exclusions, data from 4938 respondents were available. Two percent (n = 96) reported having been screened. Multiple logistic regression identified ovarian cancer worry, contact with an obstetrician-gynecologist, and family history of ovarian cancer as independently associated with screening. Based on self-reported family histories, 27 women had pedigrees consistent with high risk of ovarian cancer, but none of those women reported having been screened. CONCLUSION: Ovarian cancer screening is rare. Women at high risk of it might not be getting recommended screening.

Aged↗
PubMed2000

MAM: a "new" high-incidence antigen found on multiple cell lines.

BACKGROUND: Three women have been identified with an antibody to a "new" high-incidence antigen found on multiple cell lines. CASE REPORTS: The proposita, M.A.M., presented during her third pregnancy with an antibody reacting with all RBCs tested except her own. She delivered a thrombocytopenic infant with a 3+ DAT, but without symptoms of HDN. The second example, A.N., presented during her third pregnancy with an antibody reacting with all RBCs tested except her own and those of M.A.M. She delivered a slightly thrombocytopenic but severely anemic infant. The third example, F.K., a sister of A.N., has an antibody reacting with all RBCs tested except her own and those of M.A.M. and A.N. CONCLUSION: This "new" high-incidence antigen has been named MAM and assigned high-incidence antigen number 901016 by the International Society of Blood Transfusion. The corresponding antibody, anti-MAM, has been shown to cause HDN and has the potential to shorten RBC survival after the transfusion of incompatible RBC units, as determined by monocyte monolayer assay. Immunoblotting and flow cytometry show that this new antibody reacts with various WBC lines in addition to RBCs. This antibody also appears to react with platelets in some assays.

Adult↗
PubMed2000

Intensive care unit telemedicine: alternate paradigm for providing continuous intensivist care.

OBJECTIVE: Intensive care units (ICUs) account for an increasing percentage of hospital admissions and resource consumption. Adverse events are common in ICU patients and contribute to high mortality rates and costs. Although evidence demonstrates reduced complications and mortality when intensivists manage ICU patients, a dramatic national shortage of these specialists precludes most hospitals from implementing an around-the-clock, on-site intensivist care model. Alternate strategies are needed to bring expertise and proactive, continuous care to the critically ill. We evaluated the feasibility of using telemedicine as a means of achieving 24-hr intensivist oversight and improved clinical outcomes. DESIGN: Observational time series triple cohort study. SETTING: A ten-bed surgical ICU in an academic-affiliated community hospital. PATIENTS: All patients whose entire ICU stay occurred within the study periods. INTERVENTIONS: A 16-wk program of continuous intensivist oversight was instituted in a surgical ICU, where before the intervention, intensivist consultation was available but there were no on-site intensivists. Intensivists provided management during the intervention using remote monitoring methodologies (video conferencing and computer-based data transmission) to obtain clinical information and to communicate with on-site personnel. To assess the benefit of the remote management program, clinical and economic performance during the intervention were compared with two 16-wk periods within the year before the intervention. MEASUREMENTS AND MAIN RESULTS: ICU and hospital mortality (observed and Acute Physiology and Chronic Health Evaluation III, severity-adjusted), ICU complications, ICU and hospital length-of-stay, and ICU and hospital costs were measured during the 3 study periods. Severity-adjusted ICU mortality decreased during the intervention period by 68% and 46%, compared with baseline periods one and two, respectively. Severity-adjusted hospital mortality decreased by 33% and 30%, and the incidence of ICU complications was decreased by 44% and 50%. ICU length of stay decreased by 34% and 30%, and ICU costs decreased by 33% and 36%, respectively. The cost savings were associated with a lower incidence of complications. CONCLUSIONS: Technology-enabled remote care can be used to provide continuous ICU patient management and to achieve improved clinical and economic outcomes. This intervention's success suggests that remote care programs may provide a means of improving quality of care and reducing costs when on-site intensivist coverage is not available.

APACHE↗
PubMed2000

Social deprivation increases cardiac hospitalisations in chronic heart failure independent of disease severity and diuretic non-adherence.

OBJECTIVE: To examine whether social deprivation has any independent effect on emergency cardiac hospitalisations in patients with chronic heart failure (CHF). DESIGN: Cohort study of 478 patients with CHF who had been hospitalised before 1993 and who were followed up during 1993 and 1994. SETTING: Emergency admissions within Tayside acute hospitals. PATIENTS: 478 CHF patients who had a previous myocardial infarction, a previous CHF admission, and were on diuretic treatment. MAIN OUTCOME MEASURES: Emergency hospital admissions are divided into those for all causes and those for cardiac causes only. RESULTS: Social deprivation was significantly associated with an increase in the number of cardiac hospitalisations (p = 0.007). This effect was mainly caused by increasing the proportion of patients hospitalised in each deprivation category (26% in deprivation category 1-2 versus 40% in deprivation category 5-6, p = 0.03). This effect of deprivation was independent of disease severity, as judged by the dose of prescribed diuretic, the death rate, and the duration of each hospital stay. Non-adherence with diuretic treatment could not account for these findings either. CONCLUSIONS: Social deprivation increases the chance of a CHF patient being rehospitalised independently of disease severity. Possible explanations are that doctors who look after socially deprived patients have a lower threshold for cardiac hospitalisation of their patients, or that social deprivation alters the way a CHF patient accesses medical care during decompensation. Understanding how social deprivation influences both doctor and patient behaviour in the prehospital phase is now crucial in order to reduce the amplifying effect that social deprivation appears to have on cardiac hospitalisations.

Aged↗
PubMed2000

Hypertension and its treatment in postmenopausal women: baseline data from the Women's Health Initiative.

Little is known about the patterns of treatment and adequacy of blood pressure control in older women. The Women's Health Initiative, a 40-center national study of risk factors and prevention of heart disease, breast and colorectal cancer, and osteoporosis in postmenopausal women, provides a unique opportunity to examine these issues in the largest, multiethnic, best-characterized such cohort. Baseline data from the initial 98 705 women, aged 50 to 79 years, enrolled were analyzed to relate prevalence, treatment, and control of hypertension to demographic, clinical, and risk-factor covariates, and logistic regression analyses were performed to estimate odds ratios after adjusting for multiple potential confounders. Overall, 37.8% of the women had hypertension, which is defined as systolic blood pressure >/=140 mm Hg and/or diastolic blood pressure >/=90 mm Hg or being on medication for high blood pressure; 64.3% were treated with drugs, and blood pressure was controlled in only 36.1% of the hypertensive women, with lower rates of control in the oldest group. After adjustment for multiple covariates, current hormone users had higher prevalence than did nonusers (odds ratio 1.25). Hypertensive women had more comorbid conditions than did nonhypertensive women, and women with comorbidities were more likely to be treated pharmacologically. Diuretics were used by 44.3% of hypertensives either as monotherapy or in combination with other drug classes. As monotherapy, calcium channel blockers were used in 16%, angiotensin-converting enzyme inhibitors in 14%, beta-blockers in 9%, and diuretics in 14% of the hypertensive women. Diuretics as monotherapy were associated with better blood pressure control than any of the other drug classes as monotherapy. In conclusion, hypertension in older women is not being treated aggressively enough because a large proportion, especially those most at risk for stroke and heart disease by virtue of age, does not have sufficient blood pressure control.

Age Factors↗
PubMed2000

Tramadol and seizures: a surveillance study in a managed care population.

STUDY OBJECTIVE: To investigate the occurrence of tramadol-associated seizures. DESIGN: Retrospective cohort and case-control studies. SETTING: UnitedHealth Group-affiliated independent practice model health plans, from different regions of the United States, contracting with large networks of physicians. INTERVENTION: Analysis of administrative data from a large U.S. managed care population. PATIENTS: A cohort of 9218 adult tramadol users and 37,232 concurrent nonusers. MEASUREMENTS AND MAIN RESULTS: Fewer than 1% of users (80) had a presumed incident seizure claim after the first tramadol prescription. Risk of seizure claim was increased 2- to 6-fold among users adjusted for selected comorbidities and concomitant drugs. Risk was highest among those aged 25-54 years, those with more than four tramadol prescriptions, and those with history of alcohol abuse, stroke, or head injury. A case-control study among users was conducted to validate incident seizure outcomes from medical records. Only eight cases were confirmed, and all had cofactors associated with increased seizure risk. CONCLUSION: In a general population, risk of seizure may be associated with long-term therapy with tramadol or the presence of cofactors, or confined to a small sensitive population subset.

Adolescent↗
PubMed2000

Implementing continuing education strategies for family physicians to enhance asthma patients' quality of life.

The goal of the study was to provide asthma-related continuing medical education (CME) to family physicians with the objective of improving patient outcomes. Using a quasi-experimental design in a single community, the intervention included academic detailing, a case-based workshop, newsletters, medical grand rounds, and patient-centered education materials. Outcome measures included physician participation in CME; patient self-reported quality of life, asthma knowledge, asthma self-management, medication use, and health service utilization before and after the intervention; and physician feedback. Our results indicated that 78% of family physicians participated in one or more of the CME activities. The majority of physicians provided positive feedback on the use of the intervention both from their own and their patients' perspectives. Academic detailing increased the involvement of physicians in CME. We concluded that there was a statistically significant improvement in patients' quality of life, whereas changes in patients' knowledge, behavior, and health service use were positive but not statistically significant. Methodological factors are identified that could improve the effectiveness of future studies.

Adolescent↗
PubMed2000

Rural residency tracks in family practice: graduate outcomes.

BACKGROUND: Because the distribution of physician services in the rural United States continues to be a problem, rural residency tracks in family practice have been developed as a strategy to acculturate residents into a rural practice model. Residents complete the first year of training in an urban-based program and the last 2 years in a rural community. METHODS: We surveyed all 77 graduates of 13 nationally distributed rural training tracks that had graduates between 1988 and 1997. RESULTS: The response rate was 83% (n = 64). Seventy-six percent of respondents practice in a rural community, and 61% practice in federally designated health professional shortage areas. A total of 69% of respondents admitted patients to rural hospitals, 67% provided labor and delivery services, and 48% performed Cesarean sections. Existing physician groups were major influences on practice location. Thirty-nine percent were near their hometown, and 45% were near the community in which they completed residency training. Only 14% had a financial obligation to the community, and 94% reported that their rural training was adequate or better. CONCLUSIONS: Most graduates of rural training tracks have located their practice sites in rural communities, and most graduates provide labor and delivery services. Location decisions were associated with existing physician groups, hospitals, hometowns, and proximity to training sites.

Delivery of Health Care↗
PubMed2000

Ovarian cancer tumor marker behavior in asymptomatic healthy women: implications for screening.

Ovarian cancer screening protocols generally have been limited by inadequate recognition of the normal behavior of tumor markers in women at risk of ovarian cancer. We have characterized the behavior of five serum tumor markers in a large cohort of healthy women and examined the implications for screening. Serial measurements of CA125, HER-2/neu, urinary gonadotropin peptide, lipid-associated sialic acid, and Dianon marker 70/K were obtained during 6 years of follow-up of 1257 healthy women at high risk of ovarian cancer. We analyzed individual-specific tumor marker behavior and explored methods that can exploit this information to develop individual-specific screening rules. These five tumor markers behaved approximately independently. Substantial heterogeneity was observed among women in the behavior of each tumor marker, particularly CA125. Intraclass correlation (ICC), or the proportion of total variability that occurs between individuals, was approximately 0.6 for log-transformed CA125 and urinary gonadotropin peptide, and less than 0.4 for the other markers. This degree of tumor marker heterogeneity among healthy women, and the relative independence of these markers, has important implications for screening and diagnostic tests. Independence of markers results in the clinically useful fact that the combined false positive rate from screening with multiple markers may be estimated by the sum of individual false positive rates. Heterogeneity of tumor marker patterns in healthy women implies that a fixed screening cutoff level is suboptimal to a degree that depends strongly on ICC. Using information on longitudinal measurements and ICC, individual-specific screening rules may be developed with the potential to improve early detection of ovarian cancer.

Adult↗
PubMed2000

The politics of peanut butter.

Conflicting studies and special interest groups make developing policies to protect public health contentious and chaotic. How can lawmakers recognize 'sound' science and make good decisions?

Consumer Product Safety↗
PubMed1999

Specialized ability of thymic epithelial cells to mediate positive selection does not require expression of the steroidogenic enzyme p450scc.

Thymic epithelial cells are uniquely efficient in mediating positive selection, suggesting that in addition to providing peptide/MHC complexes for TCR ligation, they may also provide additional support for this process. Recent studies have shown that although engagement of either the TCR or glucocorticoid (GC) receptors can individually induce apoptosis in thymocytes, together these signals are mutually antagonistic. This had led to the suggestion that local GC production by thymic epithelial cells, by opposing TCR signaling for apoptosis, provides the basis of the ability of these cells to mediate thymocyte positive selection. In this paper we have examined this possibility directly and shown that highly purified cortical epithelial cells, which have the functional ability to mediate positive selection in reaggregate cultures, do not express mRNA for the key steroidogenic enzyme P405scc. Thus we conclude that the ability of thymic epithelial cells to support positive selection does not rely on their ability to produce GC. However, we find that P450scc mRNA is up-regulated in thymocytes on the initiation of positive selection, raising the possibility that any local protective effect of steroid production is mediated at the level of thymocytes themselves.

Animals↗