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Biomedical subjects

R N Thompson

Publications and source records attributed to R N Thompson.

At least 19 recordsLinked to original sources
PubMed2005

Electrophysiological and behavioral phenotype of insulin receptor defective mice.

The olfactory bulb expresses one of the highest levels of insulin found in the brain. A high level of expression of the concomitant insulin receptor (IR) kinase is also retained in this brain region, even in the adult. We have previously demonstrated in a heterologous system that insulin modulates the voltage-dependent potassium channel, Kv1.3, through tyrosine phosphorylation of three key residues in the amino and carboxyl terminus of the channel protein. Phosphorylation also induces current suppression of the Kv1.3-contributed current in cultured olfactory bulb neurons (OBNs) of rodents. In order to explore the behavioral importance of this kinase-induced modulation of the channel for the olfactory ability of the animal, mice with a targeted-gene deletion of the insulin receptor were electrophysiologically and behaviorally characterized. Mice heterozygous for the insulin receptor kinase (IR+/-) gene performed the same as wild-type (+/+) mice when challenged with a traditional, non-learning-based task to test gross anosmia. There was also no significant difference across the two genotypes in tests designed to measure exploratory behavior or in a battery of systems physiology experiments designed to assess metabolic energy usage (locomotion, ingestive behaviors, weight, oxygen consumption, and respiratory quotient). Object memory recognition tests suggest that IR+/- mice have an impairment in recognition of familiarized objects; IR+/- mice demonstrate poor performance for both short-term (1 h) and long-term (24 h) memory tests in comparison to that of wild-type mice. Electrophysiological experiments indicate that mitral cell neurons cultured from both heterozygous and homozygous-null mice (IR+/- and IR-/-) have an decreased peak current amplitude compared with that recorded for wild-type (+/+) animals matched for days in vitro (DIV). These data indicate that the loss of one allele of the IR kinase gene modifies the electrical phenotype of the mitral cell neurons in the olfactory bulb without a change in gross olfactory ability. Given our findings that there are no significant changes in metabolic balance of the IR (+/-) mice but some impairment in memory retention, future experiments testing for specific olfactory behaviors or functional deficits in IR-/+ mice models of diabetes will need to either be tasks that do not require learning or will require a different model (such as diet-induced diabetes) that may evoke a stronger phenotype.

Animals↗
PubMed2004

Kv1.3 channel gene-targeted deletion produces "Super-Smeller Mice" with altered glomeruli, interacting scaffolding proteins, and biophysics.

Mice with gene-targeted deletion of the Kv1.3 channel were generated to study its role in olfactory function. Potassium currents in olfactory bulb mitral cells from Kv1.3 null mice have slow inactivation kinetics, a modified voltage dependence, and a dampened C-type inactivation and fail to be modulated by activators of receptor tyrosine signaling cascades. Kv1.3 deletion increases expression of scaffolding proteins that normally regulate the channel through protein-protein interactions. Kv1.3-/- mice have a 1,000- to 10,000-fold lower threshold for detection of odors and an increased ability to discriminate between odorants. In accordance with this heightened sense of smell, Kv1.3-/- mice have glomeruli or olfactory coding units that are smaller and more numerous than those of wild-type mice. These data suggest that Kv1.3 plays a far more reaching role in signal transduction, development, and olfactory coding than that of the classically defined role of a potassium channel-to shape excitability by influencing membrane potential.

14-3-3 Proteins↗
PubMed2003

Natural killer cells in the synovial fluid of rheumatoid arthritis patients exhibit a CD56bright,CD94bright,CD158negative phenotype.

BACKGROUND: Natural killer (NK) cells play an important role in several animal models of autoimmunity by modulating T-cell responses, but it is unclear whether human NK cells have similar functions. METHODS: We characterized the phenotype of NK cells in synovial fluid (SF) and peripheral blood (PB) of patients with rheumatoid arthritis (RA) and in healthy control subjects using flow cytometry and quantitative PCR. RESULTS: The proportions of NK cells in PB and SF of RA patients were not significantly different from those in healthy PB. However, the SF NK cell phenotype was strikingly different, with increased CD94 and CD56 densities and greatly reduced proportions of cells expressing CD158a/b. These cells also had reduced mRNAs coding for CD158a/b and low perforin levels compared with RA PB and healthy PB NK cells. CONCLUSIONS: We identified a novel phenotype of SF NK cells that is of potential significance in RA. Experiments are now under way to determine the function of these SF NK cells and their potential role in RA.

Adult↗
PubMed2003

Bilateral distal fibular and tibial stress fractures associated with heavy smoking.

An unusual case of simultaneous bilateral stress fractures of the distal tibia and fibula in a 45 year old white woman is described. The onset of symptoms was not associated with a specific episode of trauma, sporting activity, or identifiable inflammatory predisposing cause. Her bone density scan, bone profile, and biochemistry were all normal. Although stress fractures are well recognised, bilateral distal tibial and fibular fractures are particularly rare. A high degree of awareness is required for early diagnosis.

Female↗
PubMed2001

Conceptual dilemmas in evaluating individuals with severely impaired consciousness.

States of severely impaired consciousness (SIC) are characterized by cognitive and motor limitations. This case report describes a 45-year-old female with impaired consciousness who began to 'walk'. She initially presented to the hospital unresponsive and was subsequently diagnosed with metabolic encephalopathy due to severe hypoglycaemia. Traditional indices of consciousness indicated a low level of responsiveness; however, during physical therapy, she displayed reciprocal walking movements when lifted to a standing position by two therapists. Despite her ability to walk increased distances during and after neurorehabilitation, she was unable to consistently demonstrate responses indicative of higher levels of consciousness. This case illustrates the challenge of rating patients with limited behavioural repertoire using established measures of impaired consciousness.

Brain Diseases, Metabolic↗
PubMed2000

Transient high temperatures in mantle plume heads inferred from magnesian olivines in Phanerozoic picrites.

Both scaled laboratory experiments and numerical models of terrestrial mantle plumes produce 'balloon-on-a-string' structures, with a bulbous head followed by a stem-like tail. Discussions have focused on whether their initial upwelling heads are hotter than the tails or cooler, as a result of entrainment of ambient mantle during ascent, and also on whether initial plume upwelling is a newtonian or non-newtonian process. The temperature of the mantle delivered to the base of the lithosphere is a critical parameter in such debates. Dry continental magmas can normally contribute little to this topic because their hottest (ultramafic) examples can be expected to be trapped, owing to their density, beneath the Moho. Here we report a rare case in which olivine (with 93.3% forsterite; Mg2SiO4) phenocrysts, precipitated from an unerupted komatiitic melt (approximately 24% MgO) of the Tristan mantle plume head 132 Myr ago, were carried to upper-crust levels in northwest Namibia by less Mg-rich (9.6-18.5% MgO) magmas. We infer that the hidden melt, generated when the plume impinged on the base of the lithosphere, originated in the mantle with a potential temperature of approximately 1,700 degrees C. This is approximately 400 degrees C above ambient and much hotter than the temperatures previously calculated for steady-state Phanerozoic mantle plumes. Published data show that the same conclusion can be reached for the initial Iceland and Galapagos plumes.

Journal Article↗
PubMed2000

The cardiac anxiety questionnaire: development and preliminary validity.

Heart-focused anxiety (HFA) is the fear of cardiac-related stimuli and sensations because of their perceived negative consequences. Although HFA is common to a wide variety of persons who experience chest pain and distress, it often is unrecognized and misdiagnosed, particularly in cardiology and emergency room patients without and with heart disease. To address these concerns, this article reports on the development and preliminary psychometric evaluation of the Cardiac Anxiety Questionnaire (CAQ) designed to measure HFA. In Study 1, 188 cardiology patients completed the CAQ. Item and factor analyses indicated a three-factor solution pertaining to heart-related fear, avoidance, and attention. Reliability analysis of the 18-item CAQ revealed good internal consistency of the total and subscale scores. In Study 2, 42 patients completed the CAQ and several other anxiety-related questionnaires to assess its convergent and divergent properties. Although preliminary validity results are promising, further psychometric study is necessary to cross-validate the CAQ, examine its test-retest reliability, and confirm the stability of the factor structure. Taken together, the CAQ appears to assess HFA, and may therefore be a useful instrument for identifying patients with elevated HFA without and with heart disease.

Coronary Angiography↗
PubMed1999

The psychological impact of stalking on female undergraduates.

This study examined the psychological impact of stalking upon female undergraduates, a population previously determined to experience a surprising stalking prevalence rate. Despite common understanding that stalking has deleterious effects, there have been no previous efforts to systematically assess them with standardized measures. Thirty-six female stalking victims were compared with 43 females who had been harassed and 48 controls. Psychological impact was assessed with the Posttraumatic Stress Disorder Scale, the Symptom Checklist-90-R, and the Self-Report Interpersonal Trust Scale. Stalked subjects endorsed significantly more PTSD symptoms and with greater severity than the harassed or control subjects. Stalked subjects also had significantly higher scores on several subscales of the SCL-90, and had significantly higher positive symptom totals and distress indices.

Adolescent↗
PubMed1996

Duodenal mucosal ferritin in rheumatoid arthritis: implications for anaemia of chronic disease.

Anaemia is a common feature of rheumatoid arthritis (RA) and other chronic diseases. Among the alterations in iron metabolism contributing to this effect is a decrease in intestinal iron absorption. The mechanism for this is unknown, but might involve a 'mucosal block' process similar to that proposed in iron overload, whereby increased expression of an enterocyte storage protein binds absorbed iron and prevents its transfer to the circulation. We examined the effect of disease-modifying therapy on ferritin expression in duodenal mucosa in RA to determine whether it may play a role in the 'mucosal block' process. Endoscopic small bowel biopsies were obtained from 11 patients with active RA both before, and 6 months after, a course of either gold or methotrexate (MTX). Mucosal ferritin levels in small bowel and stomach were measured by radioimmune assay. Duodenal mucosal ferritin decreased significantly following treatment (p < 0.05). There were no changes in gastric mucosal ferritin. The fall in duodenal mucosal ferritin correlated with indices of disease activity at start of therapy, and the largest decreases were in those patients showing the best response to treatment in terms of a fall in inflammatory markers. Site-specific changes in mucosal ferritin may underlie the altered iron absorption observed in active inflammatory disease by modifying the enterocyte 'mucosal block'.

Adult↗
PubMed1993

Intestinal absorption in patients with rheumatoid arthritis treated with methotrexate.

Twelve patients with rheumatoid arthritis treated for at least 12 months with methotrexate and 11 matched rheumatoid arthritis controls underwent a standard d-xylose absorption test. No patients had any pre-existing clinical of biochemical evidence of malabsorption. No significant difference was observed in the 1 hour plasma d-xylose estimation between methotrexate treated patients and controls. The 2 to 5 hour urinary excretion ratio, however, was significantly lower in the methotrexate-treated group compared with controls indicating a minor degree of malabsorption. Six of the methotrexate treated patients and 5 of the controls underwent endoscopic duodenal biopsy but neither group demonstrated any significant histological changes. In conclusion, methotrexate therapy in patients with rheumatoid arthritis produces mild intestinal malabsorption.

Aged↗
PubMed1993

Small bowel infarction in association with giant cell arteritis.

Giant cell arteritis is not uncommonly found in extracranial arteries in postmortem studies of patients with temporal arteritis. Presentation with vasculitis involving extracranial arteries is, however, unusual. This report describes a case of giant cell arteritis presenting with and complicated by infarction of the small bowel. Following surgical resection of the infarcted segment of bowel and commencement of steroid therapy, the patient is now well and free of symptoms. The literature concerning extracranial and in particular small bowel giant cell arteritis is reviewed.

Aged↗
PubMed1990

Estimation of serum V kappa IIIb light chains in rheumatoid arthritis and correlation with CD5-positive B-cells.

The presence of V kappa IIIb light chains in the sera of rheumatoid arthritis (RA) patients has been evaluated by an enzyme-linked immunosorbent assay (ELISA). V kappa IIIb light chains have been confirmed to be largely restricted to IgM, and were rarely detected in the IgG fraction of sera. The concentration of total serum V kappa IIIb did not significantly vary with age, nor did it correlate with IgM-rheumatoid factor (RF) titre. Although total serum V kappa IIIb was not significantly increased in RA patients compared with matched controls, IgM-RFs frequently contained V kappa IIIb. Using flow cytometry, CD5-positive B-cells were not increased in these RA patients compared with healthy laboratory control personnel. Furthermore, there was no direct correlation between total serum IgM V kappa IIIb content and CD5-positive B-cell numbers in peripheral blood.

Adult↗