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Biomedical subjects

C Wilson

Publications and source records attributed to C Wilson.

At least 253 records · Page 14Linked to original sources
PubMed1996

Molecular mimicry: the geographical distribution of immune responses to Klebsiella in ankylosing spondylitis and its relevance to therapy.

The discovery that HLA-B27 is linked to ankylosing spondylitis (AS) and HLA-DR1/DR4 to rheumatoid arthritis (RA) has provided new approaches to the study of the possible causation of these diseases. Several theories have been proposed to explain these associations but only one, namely "molecular mimicry", has provided a specific aetiological agent for each of these diseases. Molecular mimicry between HLA-B27 and two molecules in Klebsiella microbes: nitrogenase and pullulanase D has been reported whilst in Proteus microbes, the haemolysin molecule shows sterochemical similarity to HLA-DR1/DR4. Elevated immune responses to Klebsiella microbes have been demonstrated in AS patients from 10 different countries and this wide geographical distribution suggests that the same aetiological agent is probably acting in producing this condition. Furthermore RA patients show similar immune responses to Proteus microbes. Whether AS or RA are caused by these bacteria can only be resolved by tissue typing all rheumatological patients early, in the course of their disease and then assessing their response to antibiotic chemotherapy in longitudinal studies involving double-blind crossover trials. It is possible that in the future, the course of AS or even RA could be modified by adequate antibiotic chemotherapy or even diets which affect the substrates on which these bacteria grow.

Antibodies, Bacterial↗
PubMed1996

The use of a low starch diet in the treatment of patients suffering from ankylosing spondylitis.

The majority of ankylosing spondylitis (AS) patients not only possess HLA-B27, but during active phases of the disease have elevated levels of total serum IgA, suggesting that a microbe from the bowel flora is acting across the gut mucosa. Biochemical studies have revealed that Klebsiella bacteria, not only possess 2 molecules carrying sequences resembling HLA-B27 but increased quantities of such microbes are found in fecal samples obtained from AS patients and such patients have Crohn's like lesions in the ileo-caecal regions of the gut. Furthermore AS patients from 10 different countries have been found to have elevated levels of specific antibodies against Klebsiella bacteria. It has been suggested that these Klebsiella microbes, found in the bowel flora, might be the trigger factors in this disease and therefore reduction in the size of the bowel flora could be of benefit in the treatment of AS patients. Microbes from the bowel flora depend on dietary starch for their growth and therefore a reduction in starch intake might be beneficial in AS patients. A "low starch diet" involving a reduced intake of "bread, potatoes, cakes and pasta" has been devised and tested in healthy control subjects and AS patients. The "low starch diet" leads to a reduction of total serum IgA in both healthy controls as well as patients, and furthermore to a decrease in inflammation and symptoms in the AS patients. The role of a "low starch diet" in the management of AS requires further evaluation.

Clinical Trials as Topic↗
PubMed1996

GSK3: a SHAGGY frog story.

Glycogen synthase kinase 3 was discovered in mammals several years ago but only recently has it become clear that this enzyme is acutely regulated by hormones such as insulin and by growth factors. In mammals, it appears to be controlled by a signalling pathway linked to phosphoinositide 3-kinase and may regulate a range of biosynthetic processes. Evidence is now accumulating that GSK3 plays a key role in the regulation of cell fate and differentiation in many eukaryotic species.

Journal Article↗
PubMed1996

Vulnerability to criminal exploitation: influence of interpersonal competence differences among people with mental retardation.

A study by Wilson & Brewer (1992) has indicated that people with mental retardation are at greater risk of having a crime committed against them than age-matched cohorts from the general population. The present study was designed to test the hypothesis that this heightened vulnerability is partially explained in terms of behavioural shortcomings reflecting interpersonal competence. Twenty victims of crime and 20 nonvictims, all with mental retardation, were recruited so that means for age, adaptive behaviour and IQ were similar. Groups were compared on the Test of Interpersonal Competence and Personal Vulnerability (TICPV) developed for the present study. Results showed poorer interpersonal competence among the victims, indicating that victims had difficulty in deciding on the appropriate behaviour in some interactions. Performance on the test was shown to be internally consistent, stable over time and a valid measure of vulnerability. The study concluded with recommendations for more detailed investigation of the precise behaviours which influence risk as a first step in an attempt at remediation.

Adult↗
PubMed1996

Uncoupling learning from initial recall: the relationship between speed and memory deficits in old age.

Nettelbeck & Rabbitt (1992) found that measures of speed of performance with low knowledge requirements (four-choice reaction time, inspection time and coding-substitution) accounted substantially for age-related changes among 104 persons aged from 54 to 85 years in a number of more complex cognitive measures reflecting general fluid ability. However, the numbers of words recalled from a list after either a single brief viewing of each word, or following a cumulative learning procedure across four trials, provided an exception to this general trend, leading to the conclusion that some aspects of memory may be independent of mental speed. A follow-up of 82 of the same people 18-20 months later was designed to partition performance in a similar cumulative learning procedure into an initial first recall component and a subsequent learning component. This was accomplished by fitting individual cumulative learning data with a hyperbolic power function which met the theoretical requirement of defining separate initial recall and learning parameters. These parameters were found to be independent and it was concluded that learning involved rehearsal, whereas first recall did not. The hyperbolic power function provided a good account for 92 per cent of individual cases. Analyses which combined Nettelbeck & Rabbitt's (1992) data with new measures confirmed the reliability of these authors' results. Furthermore, it was found that first recall, but not learning, was mediated by processing speed. Learning was relatively unaffected by age-related slowing in mental speed, suggesting that Nettelbeck & Rabbitt's results were the consequence of a strong rehearsal component in their memory tasks. Thus, while mental slowing is clearly one important aspect of cognitive decline during old age, it does not constitute a sufficient explanation for changes in all areas of cognitive functioning. Specifically, age-decline in rate of learning with rehearsal appeared to be independent of slowing in speed of information processing.

Aged↗
PubMed1996

Hypoxic alterations in cellular signal transduction in shock and sepsis.

Many different cellular processes are altered by microenvironmental changes in the oxygen level, particularly hypoxia. In most cases, these hypoxic effects are mediated via alterations in cellular signal transduction pathways. Low oxygen states are generally viewed as deleterious; however, recent studies show that alterations in oxygen levels are physiologically important, influencing cells in a variety of ways. Low oxygen levels can stimulate cellular processes, such as the production of tumor necrosis factor, interleukin (IL)-1, IL-8, and nuclear factor kappa B. Kupffer cell-mediated alterations in cocultured hepatocyte function are altered by pre-exposure to hypoxic culture conditions, whereas superoxide production, intracellular pH, and adenosine triphosphate levels are decreased by hypoxia. Hypoxia followed by reoxygenation stimulates tyrosine kinase enzymes and increases intracellular calcium in a variety of cells. This review highlights recent findings concerning the manner and mechanisms by which low oxygen levels influence cell functions and cellular signaling systems. Detailed information is still lacking about the location and mechanism of most hypoxic-mediated alterations in cell signaling pathways. However, information about how factors altered by trauma and sepsis, such as Po2, acidosis, and endotoxin, effect cellular signaling pathways is rapidly emerging. Understanding the mechanism by which oxygen availability alters cell function will be important to the development of optimal therapies for post-traumatic shock and organ dysfunction.

Animals↗
PubMed1996

RNA pseudoknot modeling using intersections of stochastic context free grammars with applications to database search.

A model based on intersections of stochastic context free grammars is presented to allow for the modeling of RNA pseudoknot structures. The model runs relatively fast, having the same order running time as stochastic context free grammar parsers. The model is shown to be able to perform database searches and find RNA sequences which resemble RNA pseudoknots which bind biotin. The problem domain of RNA biotin binders has significance in the support of the RNA world model of early life on earth.

Base Sequence↗
PubMed1995

Molecular cloning, functional expression in Escherichia coli, and characterization of multiple mitogen-activated-protein kinases from tobacco.

A screening of four tobacco cDNA libraries by PCR, using degenerate oligonucleotides corresponding to motifs conserved in mitogen-activated-protein kinases from animals and yeasts, resulted in the isolation of five different PCR fragments that showed high sequence similarity to mitogen-activated-protein kinases from other organisms. Full-length cDNAs were obtained for two of these, ntf4 and ntf6, and we have previously reported the isolation of one of the other cDNAs, ntf3 [Wilson, C., Eller, N., Gartner, A., Vicente, O. & Heberle-Bors, E. (1993) Plant Mol. Biol. 23, 543-551]. The three cDNAs, ntf3, ntf4 and ntf6, as well as a mutated form of ntf3, were fused to the glutathione-S-transferase gene and expressed as fusion proteins in Escherichia coli. All three wild-type recombinant proteins, with or without the glutathione-S-transferase fragment, are capable of autophosphorylation and phosphorylate myelin basic protein, in a reaction that is more strongly supported by Mn2+ than by Mg2+, while the kinase-negative Ntf3 mutant did not show any activity. Western-blot analysis showed that the recombinant proteins autophosphorylate on tyrosine residues and are recognized by antibodies prepared against mammalian mitogen-activated-protein kinases.

Amino Acid Sequence↗
PubMed1995

Molecular mimicry and ankylosing spondylitis: possible role of a novel sequence in pullulanase of Klebsiella pneumoniae.

Molecular mimicry has been shown between two sequences of Klebsiella pneumoniae pulD secretion protein (DRDE) with HLA-B27 (DRED) and pulA (pullulanase) enzyme (Gly-X-Pro) with types I, III and IV collagen respectively. IgG antibody levels in AS patients were elevated against 16mer synthetic peptides of HLA-B27 and pulD by enzyme immunosorbent assay (ELISA) compared to controls (P < 0.001). ELISA assays against K. pneumoniae grown in the absence and presence of pullulan demonstrated significant levels of IgA antibody in AS patients compared to controls (P < 0.001). Increased IgA and IgG antibody levels to pulA and types I and IV collagen were observed in AS patients compared to controls (P < 0.001). These observations could be relevant in the sequence of molecular events in AS.

Amino Acid Sequence↗
PubMed1995

In vitro evolution of a self-alkylating ribozyme.

RNA enzymes are postulated to have catalysed all chemical reactions in the earliest living cells. This idea is now investigated in a search for alkyl transferases from a pool of random sequence RNAs. Selection for self-biotinylation yields a transfer RNA-like ribozyme that efficiently catalyses carbon-nitrogen bond formation. Ribozymes can thus promote reactions other than those involving the RNA sugar-phosphate backbone, suggesting that RNA may be capable of a broad range of catalytic activities.

Alkylation↗
PubMed1995

Cavernous malformations: results of image-guided resection.

With increased use of magnetic resonance imaging (MRI), diagnosis of cavernous malformations (CMs) has become straightforward. Surgical excision is the treatment of choice for these lesions. These malformations, though, are often small and can be difficult to localize during surgery. In these cases, stereotactic resection with a frame-based system is recommended to aid in localization of the malformation. However, use of these frame-based systems can be time consuming for the surgeon and onerous for the patient. With the advent of frameless stereotactic systems, these problems can be circumvented. Therefore, stereotactic resection of 17 CMs was performed for 15 patients over the course of 2 years at our institution during an investigative trial of a frameless stereotactic device. Eight patients presented with seizures, five patients with hemorrhage, and two patients with progressive headaches. Twelve of fifteen patients had normal neurological examination results on presentation, whereas three patients had deficits resulting from intracranial hemorrhages. All patients underwent diagnostic MRI preoperatively. Fourteen lesions were found to be cortical and subcortical; the other three lesions were in the basal ganglia, lateral ventricle, and pons. Following resection, 11 of 15 patients improved. Two patients developed postoperative deficits shortly after resection. One patient with a preoperative neurological deficit remained unchanged, and one patient had a recurrence of a deficit several months following resection. Image-guided stereotactic resection provides for easy localization of small malformations without requiring the use of a stereotactic frame or retractor and is well suited for resection of cavernous malformations.

Adolescent↗
PubMed1995

Relation of the white blood cell count to obesity and insulin resistance: effect of race and gender.

Recent reports suggest that the white blood cell (WBC) count is related to plasma insulin concentrations and insulin resistance in healthy individuals. The present study examines whether these relations are independent of obesity and the pattern of body fat distribution and tests whether race and gender affect these relations. WBC counts, insulin responses to a 75 gram oral glucose tolerance test (OGTT) and glucose disposal during a two-step hyperinsulinemic euglycemic clamp were measured in 300 men and women (149 Pima Indians, 100 whites, and 51 blacks) with a wide range of obesity. WBC counts were lower in blacks than Pima Indians or whites and tended to be higher in women than men. The subgroups were comparable in age and body weight, but percent body fat and plasma insulin concentrations were higher and glucose disposal during the glucose clamp was lower in Pima Indians than in blacks or whites. In the group as a whole, the WBC count correlated with obesity (body mass index and percent body fat), the waist to thigh ratio (an index of the pattern of body fat distribution), and plasma insulin concentrations and was negatively related to age and glucose disposal during the clamp. In multiple regression analyses, only age, race and obesity were significantly associated with the WBC count. When the analyses were restricted to Pima men, in whom correlations between the WBC count and the metabolic variables appeared the strongest, the WBC count remained significantly associated with plasma insulin concentrations, but not glucose disposal, after controlling for age and obesity. The results of this study indicate that age, race, and obesity are significantly associated with the WBC count in healthy individuals. Plasma insulin concentrations, but not insulin resistance per se, may also be weakly associated with the WBC count, but this may be population specific.

Adult↗
PubMed1995

The specificity of the anti-Proteus antibody response in tissue-typed rheumatoid arthritis (RA) patients from Brest.

Anti-Proteus mirabilis antibody titres were found to be elevated in 50 active tissue-typed French rheumatoid arthritis (RA) patients from Brest when compared to 49 healthy French controls using enzyme-linked immunosorbent assay (ELISA; P < 0.001) and indirect immunofluorescence assay (IIFA; P < 0.001). However, there was no significant elevation in antibody titres against Escherichia coli or Salmonella typhimurium in the RA patients compared to the controls when measured by ELISA. Serum levels of C-reactive protein (CRP) were also found to be significantly higher in RA patients when compared to healthy control subjects (P < 0.001). These results suggest that P. mirabilis may play an important and specific role in the triggering and persistence of RA.

Adolescent↗
PubMed1995

Effects of endothelin-1 and the ETA-receptor antagonist, BQ123, on ischemic arrhythmias in anesthetized rats.

The effects of intravenous (i.v.) infusions of exogenous endothelin-1 (ET-1, 0.05 and 0.1 nmol/kg/min) on incidence and severity of ventricular arrhythmias during 30-min period of acute myocardial ischemia were assessed in anesthetized rats. We examined the role of ETA-receptors in the proarrhythmic effects of both exogenous and endogenous ET using the ETA-receptor antagonist, BQ123. Exogenous ET-1 increased the severity and incidence of ischemic arrhythmias dose dependently. Both doses increased the total incidence of ventricular fibrillation (VF: from 30% in controls to 100 and 88% in rats given 0.05 and 0.1 nmol/kg/min ET-1, respectively); the higher dose also increased total arrhythmia count and duration of ventricular tachycardia (VT). BQ123 (10 micrograms/kg/min) completely abolished this proarrhythmic effect of exogenous ET-1. To assess the role of endogenous ET-1 in the genesis of ischemic arrhythmias, we studied the effects of a range of doses of BQ123 (5-100 micrograms/kg/min) on ischemic arrhythmias. Only one dose of BQ123 (10 micrograms/kg/min) attenuated arrhythmias by reducing total ventricular ectopic count (from 1,423 +/- 112 in controls to 677 +/- 159). The highest dose of BQ123 tested (100 micrograms/kg/min) increased arrhythmias by significantly increasing the incidence of irreversible VF (from 25 to 75%). These results suggest that exogenous ET-1 can aggravate ischemia-induced arrhythmias, an effect that is sensitive to ETA-receptor blockade. However, although endogenous ET-1 may make some contribution to the genesis of arrhythmias resulting from coronary occlusion through an action at ETA receptors, the observed proarrhythmic effect of BQ123 at high doses suggests that this may unmask an effect of ET-1 at other receptors.

Anesthesia↗