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Biomedical subjects

E A Baker

Publications and source records attributed to E A Baker.

At least 19 recordsLinked to original sources
PubMed2005

The matrix metalloproteinase system in oral squamous cell carcinoma.

BACKGROUND: The matrix metalloproteinase (MMP) system is responsible for degradation of tissue in both normal and pathological processes, including tumour invasion and metastasis. AIM: To compare tissue concentrations of components of the MMP system between tumour tissue and normal tissue in patients with oral squamous cell carcinoma, and to correlate concentrations with pathological grade of tumour. METHODS: Thirty-eight paired tissue samples from tumours and normal tissue were analysed by three laboratory techniques: firstly, enzyme linked immunosorbent assays (ELISA) in ng/mg protein for MMP-1, MMP-3, and tissue inhibitors of metalloproteinases (TIMPs) -1 and -2. Secondly, gelatinase activity assays to measure concentrations of total and endogenous active gelatinases, MMP-2 and MMP-9 (ng/mg protein). And thirdly to use quenched fluorescent substrate hydrolysis to measure total MMP activity (pM/min). RESULTS: The concentration of all MMPs was significantly higher in tumour than in normal oral tissue (p < 0.05, Mann-Whitney U-test). Tissue concentrations of some of these factors correlated with clinical and pathological indices of aggressiveness of tumours, including T-stage, N-stage, tumour differentiation, and anatomical level of involved nodes. However, the study was not powered to show statistical significance. CONCLUSION: It is the balance between proteinases and their inhibitors that controls tissue degradation at each stage of tumour invasion and metastasis. Measurement of MMPs in oral mucosal biopsy samples may establish the invasive potential of tumours at their initial presentation.

Adolescent↗
PubMed2003

The plasminogen activator and matrix metalloproteinase systems in colorectal cancer: relationship to tumour pathology.

The aim of this study was to determine the expression of proteinases and inhibitors from the matrix metalloproteinase (MMP) (MMPs 1, 2, 3, 9, tissue inhibitors of metalloproteinases (TIMPs) 1, 2) and plasminogen activator ((PA) urokinase (uPA), tissue type (tPA), uPAR, plasminogen activator inhibitors (PAIs) 1, 2) systems in colorectal cancer pathology by gelatin zymography, enzyme-linked immunosorbent assays (ELISAs) and quenched fluorescent substrate hydrolysis. The levels of all studied MMPs, uPA, uPAR, TIMP-1 and PAIs were significantly greater in tumour tissues than normal tissues. However, tPA and TIMP-2 were greater in normal colon (P<0.05, Mann-Whitney) e.g. PAI-1: tumour, median 14.9 (range 0.2-80.2) ng/mg total protein; normal, 2.1 (0.1-65.0). Tumour levels of several factors, in particular MMP-1 and PAI-1, correlated with pathology, i.e. Dukes' stage, differentiation, lymphatic or vascular invasion and tumour depth. The interactions between proteinase systems in colorectal cancer are complex and the balance between active proteinases and their inhibitors is important for extracellular matrix (ECM) degradation/remodelling at each stage of the metastatic cascade.

Adult↗
PubMed2003

Pressure-relieving properties of a intra-operative warming device.

OBJECTIVES: The primary objective of this study was to determine differences in interface pressure between four mattress combinations: a standard operating table mattress, a pressure-relieving gel pad and an under-patient warming device set at 38 degrees C (Pegasus Inditherm System) and at ambient temperature. The secondary objective was to determine whether the warming device remains stable in extreme surgical positions. METHOD: Interface pressures obtained with all four combinations were measured in 10 healthy volunteers using force sensing array technology. RESULTS: The warming device demonstrated better or equivalent pressure relief when compared with the standard gel pad. There was no significant difference in subject position 'shift' between the mattress, the gel pad and the warming device for either the Trendelenberg or reverse Trendelenberg positions. CONCLUSION: Both pressure-relieving mattresses and warming reduce intra-operative pressure damage. A mattress with both properties may further reduce pressure damage postoperatively. The warming device used in this study appears stable--subject 'slippage' was minimal in extreme positions. Research needs to be conducted among real anaesthetised patients to support these conclusions.

Adult↗
PubMed2002

Measuring gelatinase activity in colorectal cancer.

AIMS: Gelatinases (MMP-2, -9) are the most extensively studied MMPs in cancer. The aim of the study was to determine the levels of active and latent forms of the gelatinases in paired colorectal tumour and normal tissue ( n=77) and correlate these with pathological stage. METHODS: Gelatinase levels were compared following the techniques of gelatin zymography (active and latent) and the novel gelatinase activity assays (total and endogenous/active). RESULTS: Both latent and active MMP-2 and MMP-9 lysis bands (zymography) and both total (active and latent) MMP-9 and endogenous (active) MMP-9 and MMP-2 levels (activity assays) were greater in tumour than normal colorectal tissue. Total MMP-2 and MMP-9 levels as determined by activity assays correlated with both the Dukes staging (e.g. total MMP-9 in tumours: adenoma, 1.0 (0.3--3.6); Dukes A, 9.6 (2.4--35.4); Dukes B, 14.7 (1.5--103.9); Dukes C, 22.3 (2.2--57.9) and Dukes D, 37.4 (2.1--47.0) ng/mg protein) and with lymphatic invasion (e.g. total MMP-9; in tumours which had undergone lymphatic invasion, 22.7 (2.1--57.9) and those with no lymphatic invasion, 14.0 (1.5--103.9) ng/mg protein). CONCLUSIONS: Both gelatinases were upregulated in tumour tissue, however total and not endogenous active levels correlated with the pathological stage of the tumour. Therefore gelatinases may only be activated when required for tumour invasion and metastasis.

Colorectal Neoplasms↗
PubMed2002

Expression of proteinases and inhibitors in human breast cancer progression and survival.

AIMS: The expression of proteinases and their inhibitors determines the extracellular matrix (ECM) turnover in normal and pathological processes. In cancer, proteolysis is abnormally regulated, favouring ECM degradation, which aids tumour invasion and metastasis. Previous studies have determined the expression of proteinases and inhibitors in breast cancer using a variety of techniques, including immunohistochemistry; however, most have looked at the expression of individual proteinases and/or inhibitors. Therefore, the aim of the current study was to determine the simultaneous cellular expression of matrix metalloproteinases (MMPs), plasminogen activators (PAs), and tissue inhibitors of metalloproteinases (TIMPs) in patients with breast cancer and correlate this with clinical pathological staging and survival. METHODS: Immunohistochemistry was used to determine the expression of proteinases (MMP-1, MMP-2, MMP-3, MMP-9, urokinase-type PA, and tissue-type PA) and inhibitors (TIMP-1 and TIMP-2) in 44 patients with breast cancer. RESULTS: The expression of all the factors studied was stronger or equivalent in tumour cells than in fibroblasts or inflammatory cells within the tumour section. Both positive and negative trends have emerged in the correlation between the cellular expression of proteinases and inhibitors and breast tumour pathology (tumour grade, lymphovascular invasion, and Nottingham prognostic index). CONCLUSIONS: The interactions between proteinases and their inhibitors in breast cancer progression are complex. Although there are differences in the expression of these factors that relate to differences in breast cancer pathology, there are no outstanding individual factors that consistently correlate with prognosis. Therefore, different factors are probably important at different stages of the process, and the balance in the relative concentrations of proteinases and inhibitors probably determines ECM degradation in breast tumour invasion and metastasis in vivo.

Adult↗
PubMed2001

VraA (BBI16) protein of Borrelia burgdorferi is a surface-exposed antigen with a repetitive motif that confers partial protection against experimental Lyme borreliosis.

We have previously described the expression cloning of nine Borrelia burgdorferi antigens, using rabbit serum enriched for antibodies specific for infection-associated antigens, and determined that seven of these antigens were associated with infectious B. burgdorferi strain B31. One of these infection-associated antigens encoded a 451-amino-acid putative lipoprotein containing 21 consecutive and invariant 9-amino-acid repeat sequences near the amino terminus that we have designated VraA for virulent strain-associated repetitive antigen A. The vraA locus (designated BBI16 by The Institute for Genomic Research) maps to one of the 28-kb linear plasmids (designated lp28-4) that is not present in noninfectious strain B31 isolates. Subsequent PCR analysis of clonal isolates of B. burgdorferi B31 from infected mouse skin revealed a clone that lacked only lp28-4. Southern blot and Western blot analyses indicated that the lp28-4 and VraA proteins, respectively, were missing from this clone. We have also determined that VraA is a surface-exposed protein based on protease accessibility assays of intact whole cells. Furthermore, vraA expression is modestly derepressed when cells are grown at 37 degrees C relative to cells grown at 32 degrees C, suggesting that VraA is, in part, a temperature-inducible antigen. Homologues cross-reactive to B. burgdorferi B31 VraA, most with different molecular masses, were identified in several B. burgdorferi sensu lato isolates, including B. andersonii, suggesting that the immunogenic epitope(s) present in strain B31 VraA is conserved between Borrelia spp. In protection studies, only 8.3% of mice (1 of 12) immunized with full-length recombinant VraA fused to glutathione S-transferase (GST) were susceptible to infectious challenge with 10(2) B. burgdorferi strain B31, whereas naive mice or mice immunized with GST alone were infected 40% or 63 to 67% (depending on tissues assayed) of the time, respectively. As such, the partial protection elicited by VraA immunization provides an additional testable vaccine candidate to help protect against Lyme borreliosis.

Animals↗
PubMed2001

Environmental and policy determinants of physical activity in the United States.

OBJECTIVES: This study examined (1) descriptive patterns in perceived environmental and policy determinants of physical activity and (2) associations between these factors and behavior. METHODS: A cross-sectional study was conducted from 1999 to 2000 among US adults; individuals at lower income levels were oversampled. RESULTS: Availability of areas for physical activity was generally higher among men than among women. The 4 most commonly reported personal barriers were lack of time, feeling too tired, obtaining enough exercise at one's job, and no motivation to exercise. Neighborhood characteristics, including the presence of sidewalks, enjoyable scenery, heavy traffic, and hills, were positively associated with physical activity. There was a high level of support for health policy-related measures. Up to one third of individuals who had used environmental supports reported an increase in physical activity. CONCLUSIONS: An array of environmental and policy determinants, particularly those related to the physical environment, are associated with physical activity and should be taken into account in the design of interventions.

Adolescent↗
PubMed2000

Blood-brain barrier disruption and complement activation in the brain following rapid correction of chronic hyponatremia.

In previous studies we developed a rat model in which demyelination is reproducibly produced following rapid correction of chronic hyponatremia and demonstrated that the development of demyelination in this model is strongly associated with NMR indices of blood-brain barrier (BBB) disruption. Because complement is toxic to oligodendrocytes, we evaluated the hypothesis that BBB disruption precipitated by correction of hypoosmolality is followed by an influx of complement into the brain, which then contributes to the demyelination that occurs under these conditions. We studied four groups of rats with immunocytochemical analysis using primary antibodies to IgG and the C3d split-fragment of activated complement: (1) normal rats; (2) rats in which hyponatremia was maintained for 7 days; (3) chronically hyponatremic rats in which the plasma [Na(+)] was rapidly corrected with hypertonic saline administration 20 h prior to perfusion; and (4) chronically hyponatremic rats in which the plasma [Na(+)] was rapidly corrected with hypertonic saline administration 5 days prior to perfusion. In normonatremic and uncorrected hyponatremic rats only background staining was observed in areas lacking a BBB and in blood vessel walls, whereas marked increases in IgG and C3d staining were seen in the brains of rats both 20 h and 5 days after rapid correction of hyponatremia. The staining intensity was significantly correlated with the degree of neurological impairment. These results provide evidence for functional BBB disruption following rapid correction of hyponatremia and support the hypothesis that complement activation may be involved in the pathogenesis of osmotic demyelination.

Animals↗
PubMed2000

Matrix metalloproteinases, their tissue inhibitors and colorectal cancer staging.

BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in tumour invasion and metastasis. The levels of MMPs, TIMPs and total MMP activity were compared in paired colorectal tumour (n = 50) and normal tissue (n = 49) samples and correlated with clinical and pathological staging. METHODS: Gelatin zymography (MMP-2 and MMP-9), enzyme-linked immunosorbent assays (MMP-1, MMP-3, TIMP-1 and TIMP-2) and quenched fluorescent substrate hydrolysis (total MMP activity) were employed in resection specimens from 50 patients, four with adenomas and 46 with colorectal cancer. RESULTS: The levels of active MMP-2 and MMP-9 and total MMP-1, MMP-3 and TIMP-1 were significantly greater in tumour tissue than in normal colon (e.g. TIMP-1 tumour median 72 (range 25-351) versus normal 26 (4-107) ng per mg total protein content; P<0.05); however, TIMP-2 levels were significantly greater in normal tissue (P<0.05). Total MMP activity was significantly greater in tumour than in normal tissue (15 025 (1750-174 400) versus 7250 (750-354 650) pmol l-1 min-1 mg protein-1; P<0.05). Correlations were found between both MMP and TIMP levels and pathological tumour staging. MMP-1 appeared to be most important as its concentration correlated positively with Dukes staging, tumour differentiation and lymphatic invasion. CONCLUSION: The levels of the studied MMPs and total MMP activity were upregulated in colorectal tumours. MMP-1 is important in colorectal cancer progression.

Biomarkers, Tumor↗
PubMed2000

Data uses, benefits, and barriers for the behavioral risk factor surveillance system: a qualitative study of users.

The purpose of this study was to describe data use, benefits, and barriers among BRFSS users. A trained facilitator conducted eight focus groups of eight to 12 state health department employees. NUD*IST qualitative software was used to code responses. Users viewed the BRFSS as an invaluable data set. Data were used most frequently for public education, trend analyses, planning, policy support, and program evaluation. Common barriers to data use included limited availability of regional and subgroup data, lack of data analysis skills, and inadequate staff resources. Users described the BRFSS as a beneficial data source, but some barriers impede its usefulness.

Attitude of Health Personnel↗
PubMed2000

Plasminogen activator system, vascular endothelial growth factor, and colorectal cancer progression.

AIMS: To plasminogen activator system (PAS) consists of the plasminogen activators (urokinase (uPA) and tissue-type (tPA) plasminogen activators), the uPA receptor (uPAR), and the plasminogen activator inhibitors (PAI-1 and PAI-2). Plasminogen activators activate plasminogen to plasmin, which can break down extracellular matrix (ECM) components. Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells and is involved in angiogenesis. VEGF has been shown to upregulate uPA and this may facilitate tumour angiogenesis further. METHODS: PAS components and VEGF were determined by enzyme linked immunosorbent assay (ELISA) in paired colorectal tumour and normal tissue (n = 50) and correlated with pathological staging. RESULTS: uPA, uPAR, PAI-1, and VEGF values were significantly higher in tumour tissue (for example, tumour uPA: median, 2.3 (range, 0.1-6.7) ng/mg protein v normal uPA: median, 0.2 (range, 0-2.6) ng/mg protein). tPA was significantly higher in normal mucosa and there was no difference in PAI-2. uPA, uPAR, PAI-1, and VEGF values significantly correlated with each other and with Dukes's staging (uPA in adenomas: median, 0.42 (range, 0.1-1.2) ng/mg protein; upA in Dukes's B tumours: median, 2.1 (range, 0.4-4.3) ng/mg protein; and uPA in Dukes's D tumours: median, 4.0 (range, 3.7-4.2) ng/mg protein) and lymphatic invasion. In addition PAI-1 also correlated with tumour size and differentiation. CONCLUSION: The involvement of the PAS and VEGF in colorectal cancer appears to be complex. uPA, uPAR, PAI-1, and VEGF were upregulated in tumour tissue and this correlated with Dukes's staging and lymphatic invasion.

Biomarkers, Tumor↗
PubMed2000

Vasopressin V2 receptor binding is down-regulated during renal escape from vasopressin-induced antidiuresis.

This study evaluated whether renal escape from vasopressin-induced antidiuresis is associated with alterations of vasopressin V2 receptor binding in the kidney inner medulla. A radioligand binding assay was developed using a novel iodinated vasopressin V2 receptor antagonist to analyze vasopressin V2 receptor binding in kidney inner medullary tissue from three groups of rats: normal rats maintained on ad libitum water intake, rats treated with 1-deamino-[8-D-arginine]vasopressin (DDAVP), and rats treated with DDAVP that were also water loaded to induce renal escape from antidiuresis. Analysis of the binding data showed that DDAVP treatment reduced vasopressin V2 receptor binding to 72% of normal levels. Water loading induced a marked further down-regulation of vasopressin V2 receptor binding. This receptor down-regulation began by day 2 of water loading, which correlated with the initiation of renal vasopressin escape; by day 3 of water loading, vasopressin V2 receptor expression fell to 43% of DDAVP-treated levels. No differences in vasopressin V2 receptor binding affinities were found among the three groups. This study demonstrates that vasopressin V2 receptor binding capacity is down-regulated during renal escape from vasopressin-induced antidiuresis and suggests that both vasopressin-dependent mechanisms as well as vasopressin-independent mechanisms associated with water loading are involved in this receptor down-regulation.

Animals↗
PubMed1999

Principles of practice for academic/practice/community research partnerships.

CONTEXT: Researchers and practitioners are increasingly realizing that improvements in public health require changes in individual, social, and economic factors. Concurrent with this renewed awareness there has been a growing interest in working with communities to create healthful changes through academic/practice/community research partnerships. However, this type of research presents different challenges and requires different skills than traditional research projects. The development of a set of principles of practice for these types of research projects can assist researchers in developing, implementing, and evaluating their partnerships and their project activities. OBJECTIVE: This paper describes the different ways in which academics and community groups may work together, including academic/practice/community partnerships. Several principles of practice for engaging in these research partnerships are presented followed by a description of how these principles have been put into operation in a family violence prevention program. CONCLUSIONS: The principles presented are: (1) identify the best processes/model to be used based on the nature of the issue and the intended outcome; (2) acknowledge the difference between community input and active community involvement; (3) develop relationships based on mutual trust and respect; (4) acknowledge and honor different partner's "agendas"; (5) consider multi-disciplinary approaches; (6) use evaluation strategies that are consistent with the overall approach taken in the academic/practice/community partnership; and (7) be aware of partnership maturation and associated transition periods. The limitations of these principles and their application in various settings are discussed.

Academic Medical Centers↗
PubMed1999

Measurement of interface pressures in the evaluation of operating theatre mattresses.

This study compared the sacral interface pressures obtained in four mattresses (all supplied by the same manufacturer), in two positions adopted for surgical procedures, to determine the similarities and differences between them. The mattresses were all variations of the standard product used in operating departments. The null hypotheses were that there are no differences in interface pressures between the mattresses or between the two surgical positions, and that measurements are not influenced by subject body mass index. The measurement technology was also tested for reliability and suitability for intra-operative use. Sacral interface pressures of 25 healthy volunteers were recorded using each of the four mattresses (order individually randomised) in both the supine and the Lloyd Davies positions. A pressure-sensitive mat was used and one-way analysis of variance was the main statistical approach. Statistical significance was determined by p-values of < or = 0.05. One mattress recorded significantly lower interface pressures than the others and all pressures were influenced by body mass index. Surgical position was a significant factor, measurements in the Lloyd Davies position being 9.5-14.2% higher than in the supine position. The pressure measurement technique has proved to be reliable and easy to calibrate, position and use. Indications are that it can be used safely and effectively in operating departments. These results have implications for researchers and clinicians.

Adult↗
PubMed1999

Kidney aquaporin-2 expression during escape from antidiuresis is not related to plasma or tissue osmolality.

Recent results indicate that renal escape from vasopressin-induced antidiuresis is accompanied by a marked downregulation of whole kidney aquaporin-2 (AQP-2) protein and mRNA expression. However, in those studies, the escaped animals were also markedly hypo-osmolar compared to controls as a result of water loading during antidiuresis. The present studies evaluated whether systemic or local osmolality contributes to the downregulation of AQP-2 expression in this model. In the first study, two groups of 1-deamino-[8-D-arginine]-vasopressin (dDAVP)-infused rats were water-loaded; after establishment of escape, one group was then water-restricted for 4 d to reverse the escape, whereas the other group continued daily water loading. Whole kidney AQP-2 protein was measured by Western blotting, and inner medulla AQP-2 mRNA was determined by Northern blotting. Results were compared to dDAVP-infused rats fed solid chow. After 4 d of water restriction, urine volume decreased to the same level as in the rats on solid chow; however, plasma sodium concentrations and plasma osmolality remained low. Despite maintenance of significant hypo-osmolality, rats in which escape was subsequently reversed by water restriction reestablished high dDAVP-stimulated kidney levels of AQP-2 after 4 d of water restriction. In the second study, AQP-2 expression was evaluated in different regions of kidneys from water-loaded rats undergoing escape from antidiuresis. Despite markedly different interstitial osmolalities, significant downregulation of AQP-2 expression compared to dDAVP-infused control rats was seen in the inner medulla, outer medulla, and cortex. Thus, neither systemic nor interstitial osmolality appears to appreciably be correlated with downregulation of kidney AQP-2 expression during escape from antidiuresis. These results therefore suggest that additional vasopressin- and osmolality-independent factors, likely related to the effects of extracellular fluid volume expansion, also regulate kidney AQP-2 expression in rats.

Analysis of Variance↗
PubMed1999

Effects of ignition interlock license restrictions on drivers with multiple alcohol offenses: a randomized trial in Maryland.

OBJECTIVES: This investigation sought to test the effectiveness of a statewide ignition interlock license restriction program for drivers with multiple alcohol-related traffic offenses. METHODS: A total of 1387 multiple offenders eligible for license reinstatement were randomly assigned to participate in an ignition interlock program (experimental group) or in the conventional postlicensing treatment program (control group). The arrest rates of these 2 groups for alcohol traffic offenses were compared for 1 year during the ignition interlock license restriction program and for 1 year after unrestricted driving privileges were returned. RESULTS: Participation in the interlock program reduced offenders' risk of committing an alcohol traffic violation within the first year by about 65%. The alcohol traffic violation rate during the first year was significantly less for participants in the interlock program (2.4%) than for those in the control group (6.7%). However, there was no statistically significant difference between these groups in the second year, after the interlock license restriction was lifted. CONCLUSIONS: Ignition interlock license restriction programs are effective at reducing recidivism among drivers with multiple alcohol offenses, at least while the restriction is in effect.

Adult↗