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Biomedical subjects

E Ross

Publications and source records attributed to E Ross.

At least 19 recordsLinked to original sources

Molecular modeling studies of the binding characteristics of phosphates to sevelamer hydrochloride--assessing a novel technique to reduce phosphates contamination.

Recent advances in the use of polymeric materials for the remediation of phosphate from aqueous systems, including biological environments, have prompted the use of computational techniques to determine which methods are feasible to model such complex systems and to model the mechanism of binding action. In particular, Sevelamer Hydrochloride (Renagel) is used as our model polymer. A relatively simple system is constructed with a dimer of Sevelamer Hydrochloride and four phosphate ions used for capture. This work reports on molecular dynamics and Monte Carlo simulations used to determine average structure, and points of intermolecular interaction, and calculate changes in volume after the successful capture of phosphate in our model. Our resulting volume changes are of the order of 20-25%, in comparison to experimental swelling measurements on similar systems, which have an average swelling of 50-60% in aqueous media.

Models, Molecular↗

Cell surface display system for Lactococcus lactis: a novel development for oral vaccine.

The food-grade Lactococcus lactis is a potential vector to be used as a live vehicle for the delivery of heterologous proteins for vaccine and pharmaceutical purposes. We constructed a plasmid vector pSVac that harbors a 255-bp single-repeat sequence of the cell wall-binding protein region of the AcmA protein. The recombinant plasmid was transformed into Escherichia coli and expression of the gene fragment was driven by the T7 promoter of the plasmid. SDS-PAGE showed the presence of the putative AcmA' fragment and this was confirmed by Western blot analysis. The protein was isolated and purified using a His-tag affinity column. When mixed with a culture of L. lactis MG1363, ELISA and immunofluorescence assays showed that the cell wall-binding fragment was anchored onto the outer surface of the bacteria. This indicated that the AcmA' repeat unit retained the active site for binding onto the cell wall surface of the L. lactis cells. Stability assays showed that the fusion proteins (AcmA/A1, AcmA/A3) were stably docked onto the surface for at least 5 days. The AcmA' fragment was also shown to be able to strongly bind onto the cell surface of naturally occurring lactococcal strains and Lactobacillus and, with less strength, the cell surface of Bacillus sphericus. The new system designed for cell surface display of recombinant proteins on L. lactis was evaluated for the expression and display of A1 and A3 regions of the VP1 protein of enterovirus 71 (EV71). The A1 and A3 regions of the VP1 protein of EV71 were cloned upstream to the cell wall-binding domains of AcmA protein and successfully expressed as AcmA/A1 and AcmA/A3. Whole-cell ELISA showed the successful display of VP1 protein epitopes of EV71 on the surface of L. lactis. The success of the anchoring system developed in this study for docking the A1 and A3 epitopes of VP1 onto the surface of L. lactis cells opens up the possibilities of peptide and protein display for not only Lactococcus but also for other gram-positive bacteria. This novel way of displaying epitopes on the cell surface of L. lactis and other related organisms should be very useful in the delivery of vaccines and other useful proteins.

Cell Wall↗

Facilitating phenomenological interviewing by means of reflexology.

The aim of this article is to show how reflexology could facilitate phenomenological interviewing by probing the life-world of individual participants. It presents a hybrid study of phenomenological interviewing and reflexology as a holistic method of health care. In this sense, it is an interparadigmatic study, since it rests on the interface of Western and Oriental thought. This article reports on seven cases which were included in the qualitative, empirical investigation. During the sessions, reflexological readings served as impetus for inquiry into the experiences of the participants, as congestions on reflex points and along meridians were interpreted in terms of physical organs and functions. These readings were related to corresponding emotions as accepted within the reflexology paradigm. It was, however, up to the participants to inform the researcher of events and/or circumstances that caused the emotions. Thus, nonverbal data communicated information that facilitated verbal exchange concerning the life-world of each individual participant.

Adolescent↗

The effect of repetition lag on electrophysiological and haemodynamic correlates of visual object priming.

The modulation of repetition effects by the lag between first and second presentations of a visual object during a speeded semantic judgment task was examined using both scalp event-related potentials (ERPs) and event-related functional magnetic resonance imaging (efMRI). Four levels of lag were used within a single session, from zero to one, to tens of intervening stimuli, and which allowed partial separation of the effects of interference from the effects of time. Reaction times (RTs) showed that the magnitude of repetition priming decreased as lag increased. The ERP data showed two distinct effects of repetition, one between 150 and 300 ms post stimulus and another between 400 and 600 ms. The magnitude of both effects, particularly the earlier one, decreased as lag increased. The fMRI data showed a decrease in the haemodynamic response associated with repetition in several inferior occipitotemporal regions, the magnitude of which also typically decreased as lag increased. In general, and contrary to expectations, lag appeared to have mainly quantitative effects on the three types of dependent variable: there was little evidence for qualitative differences in the neural correlates of repetition effects at different lags.

Adult↗

Cough augmentation with mechanical insufflation/exsufflation in patients with neuromuscular weakness.

Adults and children with neuromuscular disease exhibit weak cough and are susceptible to recurrent chest infections, a major cause of morbidity and mortality. Mechanical insufflation/exsufflation may improve cough efficacy by increasing peak cough flow. It was hypothesised that mechanical insufflation/exsufflation would produce a greater increase in peak cough flow than other modes of cough augmentation. The acceptability of these interventions was also compared. Twenty-two patients aged 10-56 yrs (median 21 yrs) with neuromuscular disease and 19 age-matched controls were studied. Spirometry was performed and respiratory muscle strength measured. Peak cough flow was recorded during maximal unassisted coughs, followed in random order by coughs assisted by physiotherapy, noninvasive ventilation, insufflation and exsufflation, and exsufflation alone. Subjects rated strength of cough, distress and comfort on a visual analogue scale. In the neuromuscular disease group, mean +/- SD forced expiratory volume in one second was 0.8 +/- 0.6 L x s(-1), forced vital capacity 0.9 +/- 0.8 L, maximum inspiratory pressure 25 +/- 16 cmH2O, maximum expiratory pressure 26 +/- 22 cmH2O and unassisted peak cough flow 169 +/- 90 L x min(-1). The greatest increase in peak cough flow was observed with mechanical insufflation/exsufflation at 235 +/- 111 L x min(-1) (p<0.01). All techniques showed similar patient acceptability. Mechanical insufflation/exsufflation produces a greater increase in peak cough flow than other standard cough augmentation techniques in adults and children with neuromuscular disease.

Adolescent↗

The relationship between levels of mood, interest and pleasure and 'challenging behaviour' in adults with severe and profound intellectual disability.

BACKGROUND: Research on affective disorders in adults with intellectual disability (ID) suggests that depression may not present a 'classic picture' in individuals with severe and profound ID, but may include challenging behaviours, which are referred to as 'atypical symptoms', such as self-injury, aggression and irritability. The aim of the present study was to explore whether there is an association between constructs relating closely to the core symptoms of depression and challenging behaviours in adults with severe and profound ID. METHOD: Mood and levels of interest and pleasure were measured in 53 adults with severe or pro-found ID using the Mood, Interest and Pleasure Questionnaire (MIPQ). RESULTS: Two groups of adults were identified based on MIPQ scores: (1) a 'low mood' group (lowest score = 12); and (2) a comparison group (highest scoring = 12). The groups were clearly differentiated on the MIPQ (P < 0.0001), but were comparable on age, gender and medication use. The Challenging Behaviour Interview showed no difference between the two groups in self-injury, aggression or disrupting the environment. A secondary analysis revealed that participants who showed challenging behaviour scored significantly lower on the MIPQ than those who did not show challenging behaviour. CONCLUSIONS: Possible reasons for these results and considerations for future studies are discussed.

Adult↗

Characterisation and molecular cloning of an erythromycin resistance plasmid of Lactococcus lactis isolated from chicken cecum.

An erythromycin resistance plasmid, pAJ01 was isolated from Loctococcus lactis isolate C5 that was isolated from a healthy two-week-old chicken cecum. A 4 kb plasmid was transformed into plasmidless L. lactis MG1363 before a restriction endonuclease map was constructed. It was then fused with pUC19 to form pAJ02, which can replicate in Escherichia coli XLI-Blue as well as L. lactis MG1363. The plasmid was stably maintained in Lactococcus for more than 100 generations.

Animals↗

Dyslexia and visual-spatial talents: compensation vs deficit model.

There are both theoretical and empirical reasons to support the hypothesis that dyslexia is associated with enhancement of right-hemisphere, visual-spatial skills. However, the neurological evidence is neutral with respect to whether dyslexic visual-spatial abilities should be superior (a compensation model) or inferior (a deficit model). In three studies we tested the hypothesis that dyslexia is associated with superior visual-spatial skills. Individuals with dyslexia not only failed to show superiority on a range of visual-spatial tasks, even when tasks were presented without time constraints, but also demonstrated a deficit on many tasks. Whereas we found attentional problems associated with dyslexia, these did not explain our findings. Results are discussed in terms of the apparent conflict between the failure to find any visual-spatial talent associated with dyslexia and the fact that dyslexia is overrepresented in certain visual-spatial professions.

Adult↗

Accuracy of cancer-risk assessment in primary care practice.

BACKGROUND: Primary care physicians (PCPs) are expected to play a central role in assessing cancer risk. This study was designed to evaluate how accurately PCPs would triage individuals at increased risk for cancer when presented with clinical vignettes. METHODS: Surveys evaluated practice demographics, attitudes, and responses to clinical scenarios. Answers were compared with guidelines and graded for consistency with the risk assessment. RESULTS: PCPs were inaccurate in assessing risk (p < 0.0001) and inconsistent in recommending screening (p < 0.001). Older physicians were more consistent (p < 0.02). No attitudinal bias was identified. CONCLUSION: Continuing education of PCPs is important for cancer-risk assessment and management.

Education, Medical, Continuing↗

Moving towards rational pharmacological management of pain with an improved classification system of pain.

Recognition that untreated pain can have serious deleterious effects has lead to significant resources being devoted towards understanding physiology, controlling nociception and implementing standards that promise to improve treatment of pain. Recently, improved knowledge and the appreciation of the need for a polypharmaceutical approach has lead to an appreciation that the classification of pain syndromes is the best approach towards rationalising treatment approaches. Older classification approaches such as acute and chronic, neuropathic, or nociceptive have not been universally useful for the clinician [1]. These classification schemes do not recognise that patients with pain often have mixed pain syndromes and do not fall neatly into these schemes. In addition, these classification schemes cannot represent newer advances in the understanding of pain and its physiology. Due to the growing variety of treatment approaches, classification of pain syndromes is often the best first step towards understanding a patient's pathophysiological process, initiating appropriate treatment and improving patient outcomes.

Analgesics↗

In vitro quantitative chemical analysis of tattoo pigments.

BACKGROUND: The composition of cosmetic tattoos might prove relevant to their treatment by high-powered lasers. OBJECTIVES: To test the accuracy and completeness of information supplied by the tattoo ink manufacturers and to perform an elemental assay of tattoo pigments using scanning electron microscopy with energy-dispersive x-ray analysis. DESIGN: Samples of 30 tattoo inks were examined using "standardless" energy-dispersive spectrometry. This technique uses quantitative electron x-ray microanalysis. The technique reliably identifies all elements with the exception of those elements with atomic numbers less than 11. SETTING: A major national referral laboratory for microscopic examination and biochemical analysis of tissue. These results were compared with ink compositions compiled from manufacturer-supplied material safety data sheets. MAIN OUTCOME MEASURES: (1) The percentage of any given element in whole tattoo pigments. (2) The presence or absence of elements and/or compounds as recorded in material safety data sheets supplied by the tattoo ink manufacturers. RESULTS: Of the 30 tattoo inks studied, the most commonly identified elements were aluminum (87% of the pigments), oxygen (73% of the pigments), titanium (67% of the pigments), and carbon (67% of the pigments). The relative contribution of elements to the tattoo ink compositions was highly variable between different compounds. Overall, the manufacturer-supplied data sheets were consistent with the elemental analysis, but there were important exceptions. CONCLUSION: The composition of elements in tattoo inks varies greatly, even among like-colored pigments. Knowledge of the chemical composition of popular tattoo inks might aid the clinician in effective laser removal.

Electron Probe Microanalysis↗

Trimodality therapy for advanced gallbladder cancer.

We conducted a retrospective review of all patients who underwent surgical extirpation for stage III, stage IV, or recurrent carcinoma of the gallbladder. Between 1991 and 1999 ten patients underwent surgical resection for advanced gallbladder cancer. All patients received adjuvant therapy either pre- or postoperatively. Radiotherapy was used in all patients and chemotherapy in 90 per cent of patients. Two patients subsequently underwent resection for locally recurrent disease. An additional patient with stage II disease initially was also treated surgically for a local recurrence. Surgical management involved cholecystectomy and resection of various amounts of liver surrounding the gallbladder bed and regional lymphadenectomy. Contiguously involved structures were resected en bloc. Resection of recurrent disease included excision of all gross tumor. The median overall survival excluding the one 30-day mortality was 53.6 months (range 8-73 months). Four patients have survived 4 or more years, and currently four patients are alive and disease free at 73, 49, 33, and 8 months. Median disease-free interval after each resection of recurrent disease was 13.8 months (range 4-28 months). We conclude that trimodality therapy in selected patients with stage III, IV, or recurrent carcinoma of the gallbladder is possible and may result in prolonged survival.

Acute Disease↗

Altered emotional perception in alcoholics: deficits in affective prosody comprehension.

BACKGROUND: Affective prosody is a nonlinguistic aspect of language that conveys emotion and attitude during discourse. It is a dominant function of the right hemisphere. Because skills associated with the right hemisphere have been found to be impaired in alcoholics, this study explored the possibility that affective prosodic functioning may be sensitive to the effects of alcohol due to heavy persistent drinking or prenatal exposure. METHODS: Subjects were aged 25 to 58 years. Twenty-nine men and three women who met DSM-IV criteria for an alcohol use disorder with a median of 39 days of sobriety, 11 men with a probable history of fetal alcohol exposure (FAexp), and 41 age-matched control subjects of both sexes were tested by using the Aprosodia Battery. This instrument assesses affective prosodic comprehension (APC) across a range of verbal articulatory demands. RESULTS: The alcoholic group scored 2 SD below the control mean, and the FAexp group scored -5 SD regardless of whether they had ever been diagnosed with alcohol abuse. Despite their poor performance on APC, alcoholic and FAexp groups performed similarly to the control group on vocabulary, abstract reasoning, and an index of cognitive impairment that used the Shipley Institute of Living Scale. Multiple regression analyses that used nine alcohol use variables to model APC resulted in four significant contributors to the effect. These regressors were related to early exposure to ethanol and chronicity of alcohol abuse. CONCLUSIONS: Alcoholics and FAexp subjects were significantly less accurate at APC compared with controls. These alcohol-exposed subjects appear to be deficient in the ability to understand emotional valence in the speech of others, which results in errors of judgment that may impair social interactions.

Adult↗

The psychological effects of traumatic brain injury on the quality of life of a group of spouses/partners.

This study explored the psychosocial impact of traumatic brain injury on the perceived quality of life of a purposefully selected group of 14 spouses/partners of head injured persons by means of a self-administered questionnaire. Analysis of responses revealed that spouses/partners' altered communication patterns were perceived to have affected interpersonal relationships and quality of life extensively, indicating the need for speech-language therapy. Decreased income was noted due to the low incidence of return to work. Participants reported changes in family relationships, particularly between the injured person and their children as well as deterioration in marital relationships, suggesting the necessity for family therapy and marital counselling. Various emotional reactions were documented in response to injury. Yet most respondents expressed acceptance of their new roles and responsibilities despite the difficulties entailed. Since injured persons were dependent on their spouses/partners to a large extent, most of the latter reported feeling tied down. Loneliness predominated as a social consequence despite the support of pre-injury friendships. In terms of coping resources, friends, family, religion and support groups were perceived to be most effective. Results are discussed in terms of their clinical implications for psychosocial rehabilitation and spouse/partner counselling.

Adult↗

Persistent induction of the chemokine receptor CXCR4 by TGF-beta 1 on synovial T cells contributes to their accumulation within the rheumatoid synovium.

Chemokines and their receptors determine the distribution of leukocytes within tissues in health and disease. We have studied the role of the constitutive chemokine receptor CXCR4 and its ligand, stromal-derived factor-1 (SDF-1) in the perivascular accumulation of T cells in rheumatoid arthritis. We show that synovial T cells, which are primed CD45RO+CD45RBdull cells and consequently not expected to express constitutive chemokine receptors, have high levels of the chemokine receptor CXCR4. Sustained expression of CXCR4 was maintained on synovial T cells by specific factors present within the synovial microenvironment. Extensive screening revealed that TGF-beta isoforms induce the expression of CXCR4 on CD4 T cells in vitro. Depletion studies using synovial fluid confirmed an important role for TGF-beta1 in the induction of CXCR4 expression in vivo. The only known ligand for CXCR4 is SDF-1. We found SDF-1 on synovial endothelial cells and showed that SDF-1 was able to induce strong integrin-mediated adhesion of synovial fluid T cells to fibronectin and ICAM-1, confirming that CXCR4 expressed on synovial T cells was functional. These results suggest that the persistent induction of CXCR4 on synovial T cells by TGF-beta1 leads to their active, SDF-1-mediated retention in a perivascular distribution within the rheumatoid synovium.

Arthritis, Rheumatoid↗

The small GTPase, Rap1, mediates CD31-induced integrin adhesion.

Integrin-mediated leukocyte adhesion is a critical aspect of leukocyte function that is tightly regulated by diverse stimuli, including chemokines, antigen receptors, and adhesion receptors. How cellular signals from CD31 and other adhesion amplifiers are integrated with those from classical mitogenic stimuli to regulate leukocyte function remains poorly understood. Here, we show that the cytoplasmic tail of CD31, an important integrin adhesion amplifier, propagates signals that induce T cell adhesion via beta1 (VLA-4) and beta2 (LFA-1) integrins. We identify the small GTPase, Rap1, as a critical mediator of this effect. Importantly, CD31 selectively activated the small Ras-related GTPase, Rap1, but not Ras, R-Ras, or Rap2. An activated Rap1 mutant stimulated T lymphocyte adhesion to intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM), as did the Rap1 guanine nucleotide exchange factor C3G and a catalytically inactive mutant of RapGAP. Conversely, negative regulators of Rap1 signaling blocked CD31-dependent adhesion. These findings identify a novel important role for Rap1 in regulating ligand-induced cell adhesion and suggest that Rap1 may play a more general role in coordinating adhesion-dependent signals during leukocyte migration and extravasation. Our findings also suggest an alternative mechanism, distinct from interference with Ras-proximal signaling, by which Rap1 might mediate transformation reversion.

Antigens, CD↗