Search PubMed⌕ Search

Biomedical subjects

A Brown

Publications and source records attributed to A Brown.

At least 55 records · Page 3Linked to original sources
PubMed2003

Autonomic dysreflexia after spinal cord transection or compression in 129Sv, C57BL, and Wallerian degeneration slow mutant mice.

To study plasticity of central autonomic circuits that develops after spinal cord injury (SCI), we have characterized a mouse model of autonomic dysreflexia. Autonomic dysreflexia is a condition in which episodic hypertension occurs after injuries above the midthoracic segments of the spinal cord. As synaptic plasticity may be triggered by axonal degeneration, we investigated whether autonomic dysreflexia is reduced in mice when axonal degeneration is delayed after SCI. We subjected three strains of mice, Wld(S), C57BL, and 129Sv, to either spinal cord transection (SCT) or severe clip-compression injury (CCI). The Wld(S) mouse is a well-characterized mutant that exhibits delayed Wallerian degeneration. The CCI model is an injury paradigm in which significant the axonal degeneration is due to secondary events and therefore delayed relative to the time of the initial injury. We herein demonstrate that the incidence of autonomic dysreflexia is reduced in Wld(S) mice after SCT and in all mice after CCI. To determine if differences in afferent arbor sprouting could explain our observations, we assessed changes in the afferent arbor in each mouse strain after both SCT and CCI. We show that independent of the type of injury, 129Sv mice but not C57BL or Wld(S) mice demonstrated an increased small-diameter CGRP-immunoreactive afferent arbor after SCI. Our work thus suggests a role for Wallerian degeneration in the development of autonomic dysreflexia and demonstrates that the choice of mouse strain and injury model has important consequences to the generalizations that may be drawn from studies of SCI in mice.

Afferent Pathways↗
PubMed2003

Successful vaccination of BALB/c mice against human hookworm (Necator americanus): the immunological phenotype of the protective response.

In this murine (BALB/c) model of necatoriasis, high levels of protection against challenge infection by Necator americanus larvae (n=300) were afforded by successive vaccinations at 14-day intervals, either subcutaneously or percutaneously, with gamma-irradiated N. americanus larvae (n=300). Percutaneous vaccination was significantly more effective than the subcutaneous route, with pulmonary larval burdens at 3 days post-infection being reduced by 97.8 vs. 89.3%, respectively, after three immunisations (P<0.05). No worms were recovered from the intestines of thrice vaccinated mice. Two percutaneous vaccinations also reduced worm burdens, by 57% in the lungs and 98% in the intestines; P<0.05. In vaccinated animals, lung pathology (mainly haemorrhage) following infection was greatly reduced compared with non-vaccinated animals. In vaccinated mice (but not in non-vaccinated mice) mast cells accumulated in the skin and were degranulated. RT-PCR analyses of mRNAs in the skin of vaccinated animals indicated increased expression of interleukin (IL)-4 relative to gamma-interferon (gamma-IFN). Lymphocytes from the axillary (skin-draining) lymph nodes of vaccinated mice, stimulated in vitro with concanavalin A, exhibited enhanced secretion of IL-4 protein and a higher IL-4/gamma-IFN protein ratio than lymphocytes from non-vaccinated animals. In vaccinated mice, levels of IgG1 and IgG3 (directed against larval excretory/secretory products) were elevated for the most part compared with those in non-vaccinated animals. These data demonstrate the successful vaccination of BALB/c mice against human hookworm infection and suggest that a localised Th2 response may be important for conferring protection against necatoriasis.

Animals↗
PubMed2003

Quantitative valence plasmon mapping in the TEM: viewing physical properties at the nanoscale.

Using a series of graphitising carbons heat treated at different temperatures, the peak position of the bulk (pi+sigma) plasmon was measured using electron energy loss spectroscopy and observed to shift between 22 and 27eV. Experimental data is presented and discussed showing the effects of the collection conditions and sample orientation upon the observed spectra. We present an empirical technique by which quantitative energy filtered transmission electron microscopy (EFTEM) maps with two energy windows selected in the plasmon region can be readily acquired and processed, the results of which may be interpreted as graphitisation maps and subsequently physical property maps. An experimentally established resolution of approximately 1.6nm makes this technique a very useful tool with which to examine nanoscale properties in microstructural regions of interest in TEM specimens such as fibre/matrix interfaces within carbon-carbon composites, multi-walled carbon nanotubes and graphitic inclusions in carbon steels. Also presented is data demonstrating the unsuitability of pi(*)-related chemical EFTEM maps in both the low-loss region and at the carbon K ionisation edge for mapping bonding in such highly anisotropic media due to the strong orientation dependence of the intensity of the transitions involved. This is followed by suggestions for wider application of the plasmon mapping technique within systems other than those based upon carbon.

Journal Article↗
PubMed2003

Differential gene expression profiles in embryonic, adult-injured and adult-uninjured rat spinal cords.

To identify genes that render the adult-injured spinal cord nonpermissive and the embryonic spinal cord permissive to regeneration, we used subtraction hybridization and suppression PCR to generate subtractive cDNA populations representing (1) genes expressed in the embryonic but not in the adult-injured or uninjured spinal cords, (2) genes expressed in the adult-injured but not in the embryonic or adult-uninjured spinal cords, and (3) genes expressed in the embryonic and adult-injured spinal cords but not in the adult-uninjured spinal cord. Between 85 and 98% of the cDNAs identified are differentially represented in each population. Genes in each cDNA population were identified by microarray hybridization. Genes involved in inflammation, apoptosis, and neuroprotection were overrepresented in injured spinal cord cDNA, whereas genes involved in cell signaling and differentiation were overrepresented in the embryonic cDNA. This gene expression profiling suggests new hypotheses regarding the genes involved in inhibition and promotion of spinal cord regeneration.

Aging↗
PubMed2003

Effect of long-term treatment with low-dose mifepristone on the endometrium.

BACKGROUND: Mifepristone in low daily doses has contraceptive potential by inhibiting ovulation and menstruation. Because follicular development is maintained, the endometrium is exposed to estrogen for prolonged periods unopposed by progesterone. METHODS: Endometrial biopsies were collected from 90 women in Edinburgh and Shanghai before (late proliferative) and 60 and 120 days after taking 2 or 5 mg mifepristone per day for 120 days. RESULTS: Ovulation and menstruation were inhibited in >90% of cycles and estrogen production was similar to that observed during the follicular phase of the control cycle. By 120 days, endometrial thickness increased significantly in women in Edinburgh but decreased in Shanghai. Endometrial histology showed inactive proliferative or cystic changes with dense stroma. There was a significant decrease in markers of proliferation, i.e. mitotic index and Ki67 staining. There were no pregnancies in a total of 200 women-months in 50 sexually active women who used no other method of contraception. CONCLUSIONS: We confirm that ovulation and menstruation were suppressed in the majority of cycles and there was asynchrony between ovarian activity and endometrial histology, which showed no signs of hyperplasia or atypia. These preliminary data suggest that daily low-dose mifepristone is potentially a safe estrogen-free contraceptive pill which has the added health benefit of amenorrhoea.

Adult↗
PubMed2003

Complex chimeras to map ligand binding sites of GPCRs.

Family 1a GPCRs are thought to bind small molecule ligands in a pocket comprising sequences from non-contiguous transmembrane helices. In this study, receptor-ligand binding determinants were defined by building a series of complex chimeras where multiple sequences were exchanged between related G-protein coupled receptors. Regions of P2Y(1), P2Y(2) and BLT(1) predicted to interact with nucleotide and leukotriene ligands were identified and receptors were engineered within their transmembrane helices to transpose the ligand binding site of one receptor on to another receptor. Ligand-induced activation of chimeras was compared with wild-type receptor activation in a yeast reporter gene assay. Binding of ligand to a P2Y(2)/BLT(1) chimera confirmed that the ligand binding determinants of BLT(1) are located in the upper regions of the helices and extracellular loops of this receptor and that they had been successfully transferred to a receptor that normally binds unrelated ligands.

Amino Acid Sequence↗
PubMed2003

Counterfactual cognitive deficit in persons with Parkinson's disease.

BACKGROUND: Counterfactuals are mental representations of alternatives to past events. Recent research has shown them to be important for other cognitive processes, such as planning, causal reasoning, problem solving, and decision making-all processes independently linked to the frontal lobes. OBJECTIVE: To test the hypothesis that counterfactual thinking is impaired in some patients with Parkinson's disease and is linked to frontal dysfunction in these patients. Methods. Measures of counterfactual processing and frontal lobe functioning were administered to 24 persons with Parkinson's disease and 15 age matched healthy controls. Results. Patients with Parkinson's disease spontaneously generated significantly fewer counterfactuals than controls despite showing no differences from controls on a semantic fluency test; they also performed at chance levels on a counterfactual inference test, while age matched controls performed above chance levels on this test. Performance on both the counterfactual generation and inference tests correlated significantly with performance on two tests traditionally linked to frontal lobe functioning (Stroop colour-word interference and Tower of London planning tasks) and one test of pragmatic social communication skills. CONCLUSIONS: Counterfactual thinking is impaired in Parkinson's disease. This impairment may be related to frontal lobe dysfunction.

Aged↗
PubMed2003

Angiotensin-converting enzyme genotype and the ventilatory response to exertional hypoxia.

The "insertion" (I) rather than "deletion" (D) variant of the human angiotensin-converting enzyme (ACE) gene is associated with both lower tissue ACE activity and elite performance at high altitude. Three genotypes, II, ID and DD, are thus represented in the population. The authors examined whether an improved ventilatory response to hypoxic exercise may contribute to this effect. Subjects (n=60; 37 male, mean+/-SEM age 23.6+/-0.6 yrs, 14 II, 30 ID, 16 DD) underwent incremental cardiopulmonary exercise testing to establish maximal oxygen uptake and ventilatory threshold (VT). Four hours later, subjects exercised for 6 mins at 50% of the workload at VT. The protocol was repeated 15 mins later while breathing 12.5+/-0.5% oxygen in nitrogen. All subject characteristics were independent of genotype, as were data during normoxic exercise. However, the hypoxia-induced rise in minute ventilation was significantly greater among those of II genotype (39.6+/-4.1% versus 27.9+/-2.0% versus 28.4+/-2.2% for II versus ID versus DD, respectively). These data are supported by a significantly greater decrease in end tidal carbon dioxide (consistent with an increase in alveolar ventilation) among those homozygous for the I allele (II -18.7+/-1.3%, ID -15.7+/-0.4%, DD -15.1%+/-1.1). The ventilatory response to hypoxic exercise is influenced by angiotensin-converting enzyme genotype. Potential implications concern high altitude performance and the pathogenesis and management of hypoxic lung disease.

Adult↗
PubMed2002

Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy.

OBJECTIVE: To explore the relationship between intraepidermal nerve fiber (IENF) density in HIV-associated sensory neuropathy (HIV-SN) to measurements of neuropathy severity and progression of HIV disease. BACKGROUND: SN affects 30% of individuals with AIDS, and treatment is often ineffective. Recombinant human nerve growth factor (rhNGF) has been proposed as a trophic factor for unmyelinated nerve fibers injured in HIV-SN, and a clinical trial has recently concluded. Skin biopsy with IENF density determination has emerged as a diagnostic test for patients with small-fiber sensory neuropathy. METHODS: Sixty-two of the 270 patients with HIV-SN who participated in the trial of rhNGF were included in a substudy examining epidermal nerve fibers. IENF density was compared with neuropathic pain intensity (measured with the Gracely Pain Scale), patient and physician global pain assessments, quantitative sensory testing, CD4 counts, and plasma HIV RNA levels both at baseline and at conclusion of the placebo-controlled phase. RESULTS: IENF density was inversely correlated with neuropathic pain as measured by patient (p = 0.004) and physician (p = 0.05) global pain assessments, but not using the Gracely Pain Scale. Decreased IENF density at the distal leg was associated with lower CD4 counts and higher plasma HIV RNA levels. IENF density measurements were stable over time. CONCLUSIONS: IENF loss at the distal leg is associated with increased neuropathic pain, lower CD4 counts, and higher plasma viral load in HIV-SN. The robustness of the longitudinal measurement of IENF density supports its use in future longitudinal studies and clinical trials.

Acquired Immunodeficiency Syndrome↗
PubMed2002

A multicentre evaluation of the diagnostic efficiency of serological investigations for C1 inhibitor deficiency.

AIM: To determine the diagnostic efficiency of assays routinely used in the investigation of hereditary angio-oedema. METHODS: Over a four year period, 1144 samples were received for analysis from 907 patients suspected of C1 inhibitor deficiency. Analyses were performed for C4 and C1 inhibitor (functional and immunochemical). Notes were reviewed retrospectively on patients with low serological indicators to determine diagnosis. RESULTS: These are the first data to indicate the sensitivity, specificity, and predictive values of the assays most frequently used to screen for C1 inhibitor deficiency. A combination of low C4 and low C1 inhibitor function has 98% specificity for C1 inhibitor deficiency in this population and a 96% negative predictive value, and is thus a very effective screen. All patients with untreated C1 inhibitor deficiency had a low C4 value. CONCLUSIONS: All patients considered for a diagnosis of C1 inhibitor deficiency should have serum examined to measure both C4 and functional C1 inhibitor. If either is normal at presentation this essentially excludes a diagnosis of C1 inhibitor deficiency. These tests can be performed sequentially. If C4 is normal it is not necessary to proceed to C1 inhibitor analysis. If C1 inhibitor function and C4 are both low then a repeat sample should be obtained to confirm the findings.

Angioedema↗
PubMed2002

Ambulatory pulmonary artery pressure monitoring during sleep and exercise in normal individuals and patients with COPD.

BACKGROUND: Pulmonary hypertension is a common complication of chronic obstructive airways disease (COPD) and its presence implies a poor prognosis. However, it is difficult to measure and its specific contribution to symptoms is difficult to quantify. A micromanometer tipped pulmonary artery catheter was used to measure pulmonary artery pressure (PAP) during sleep and on exercise. METHODS: Ten patients (five with COPD receiving long term oxygen therapy and five normal individuals) were studied. Pulmonary artery pressure was recorded continuously during two periods of sleep (breathing oxygen followed by air for the COPD group) and during exercise. RESULTS: In the COPD group PAP during sleep on oxygen was significantly lower than PAP during sleep breathing air (mean (SD) difference 9.6 (5.3) mm Hg, 95% CI 4.9 to 14.3, p= 0.016). PAP during exercise was not significantly different from PAP during sleep breathing air (mean (SD) difference 0.8 (8.9) mm Hg, 95% CI -7.0 to 8.6, p= 0.851). In normal individuals the group mean (SD) PAP was 15 (5.9) mm Hg for the first nocturnal period and 15 (5.7) mm Hg for the second nocturnal period. PAP during exercise was not significantly different from PAP during sleep breathing air (mean (SD) difference 3.3 (2.2) mm Hg, 95% CI 1.1 to 5.5, p= 0.061). CONCLUSION: In patients with COPD, PAP rose significantly during sleep to levels similar to those measured during exercise, but this could be reversed with oxygen.

Adult↗
PubMed2002

Determinants of gonorrhoea infection among STD clinic attenders in Trinidad--II: sexual behavioural factors.

Sexual behavioural factors associated with gonococcal infection among 991 STD clinic attenders in Trinidad, West Indies (WI) were determined by univariate and stepwise multiple logistic regression analysis. Casual sex (odds ratios [OR] 1.6) was the only predictor of gonorrhoea. Among males, significant associations were identified by univariate analysis between concurrent partnerships, > or =one sexual partner(s) in the past 6 months, and drug use prior to engaging in casual and/or oral sex. No significant associations were identified between gonorrhoea and sexual behaviour factors among females. This study is the first to describe sexual behaviours associated with gonococcal infection in Trinidad and to evaluate risk behaviours by gender.

Age Factors↗
PubMed2002

Determinants of gonorrhoea infection among STD clinic attenders in Trinidad--I: sociodemographic factors, knowledge, risk perception and history of STD.

We determined the prevalence of Neisseria gonorrhoeae and describe sociodemographic factors, knowledge and sexually transmitted disease (STD) history associated with gonococcal infection among 991 STD clinic attenders in Trinidad, West Indies (WI). The prevalence of gonorrhoea was 25%. Predictors for gonorrhoea were: male gender (odds ratios [OR] 3.5), age 15-19 (OR 2.5) and 20-29 years (OR 2.1), unawareness of the term STD (OR 1.5), self-perceived risk for STDs (OR 1.7) and no history of syphilis (OR 2.0). When the data were analysed by gender, significant associations were identified between gonococcal infection and age <30 years, single status, and self-perceived risk for STDs for males. Among females, significant associations existed between gonorrhoea and age <30 years, and unawareness of the term STD. This study is novel in describing sociodemographic characteristics of STD clinic attenders, and risk markers associated with gonococcal infection in Trinidad.

Adolescent↗
PubMed2001

[Can readmission after apoplexy be prevented? Post-hospital follow-up intervention for apoplexy patients].

INTRODUCTION: The aim of this study was to evaluate two models of an organised postdischarge follow-up service for stroke survivors in comparison with standard aftercare. METHODS: One hundred and fifty-five stroke patients discharged to their homes with lasting impairment were randomised as follows: 54 to follow-up home visits by a physician (INT1-HVP), 53 to instruction by a physiotherapist in their home (INT2-PI), and 48 to standard aftercare (control). Six months after discharge, data on readmission were collected. RESULTS: The readmission rate over the six-month period was 26% in the INT1-HVP group, 34% in the INT2-PI group, and 44% for the controls (p = 0.028). Multivariate analysis of the readmission risk showed a significant, favourable effect of intervention in interaction with the length of hospital stay (p = 0.0332), which indicates that the effect of intervention was strongest for patients with a long inpatient rehabilitation. DISCUSSION: Follow-up intervention after discharge seems to be a way of preventing readmission, especially for patients with a long inpatient rehabilitation.

Activities of Daily Living↗
PubMed2001

Generation of enterococci bacteria in a coastal saltwater marsh and its impact on surf zone water quality.

Elevated levels of enterococci bacteria, an indicator of fecal pollution, are routinely detected in the surf zone at Huntington State and City Beaches in southern California. A multidisciplinary study was carried out to identify sources of enterococci bacteria landward of the coastline. We find that enterococci bacteria are present at high concentrations in urban runoff, bird feces, marsh sediments, and on marine vegetation. Surprisingly, urban runoff appears to have relatively little impact on surf zone water quality because of the long time required for this water to travel from its source to the ocean. On the other hand, enterococci bacteria generated in a tidal saltwater marsh located near the beach significantly impact surf zone water quality. This study identifies a potential tradeoff between restoring coastal wetlands and protecting beach water quality and calls into question the use of ocean bathing water standards based on enterococci at locations near coastal wetlands.

Conservation of Natural Resources↗