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Biomedical subjects

C Wilson

Publications and source records attributed to C Wilson.

At least 37 records · Page 2Linked to original sources
PubMed1997

The treatment and prevention of obesity: a systematic review of the literature.

OBJECTIVE: To determine the effectiveness of interventions designed to prevent and treat obesity, and maintain weight loss. DESIGN: A systematic review of randomised controlled trials. SUBJECTS: Overweight and obese adults and children. MEASUREMENTS: Post-intervention changes in weight, fat content and fat distribution, measured relative to baseline. RESULTS: For obese children, family therapy and lifestyle modification appear to be effective in prevention and treatment, respectively. The effectiveness of interventions to prevent and treat obesity in adults remains unclear, although behavioural therapy and multicomponent strategies may be useful. Continued therapist contact appears to be useful for maintaining weight loss. Pharmacological interventions appear to be effective for up to 9 months, after which regain occurs. Surgery appears to be effective for the morbidly obese and gastric bypass is more effective than gastroplasty. In general, the methodological quality of studies was poor. CONCLUSION: Due to problems with methodological quality, it is recommended that research findings indicative of promising interventions are replicated.

Adolescent↗
PubMed1997

A prospective randomized study comparing a catheter-valve with a standard drainage system.

OBJECTIVE: To determine if the use of a catheter-valve rather than a standard drainage system decreases the morbidity associated with the use of a long-term catheter. PATIENTS AND METHODS: One hundred patients undergoing long-term catheterization were recruited into a prospective randomized study to investigate the acceptability and determine any increase in infection associated with the use of a catheter-valve, compared with the standard drainage system. Each patient participated in the study protocol for 3 months, during which the frequency of urinary tract infection was assessed, and the patients' views obtained using a standard questionnaire and by interview. RESULTS: Ninety-four patients completed the study; most (92%) were happy or satisfied with the valve, as opposed to only 35% of those using a standard drainage bag. There was no significant difference between the groups in the incidence of urinary tract infections. CONCLUSION: The patients who used the standard drainage system felt their level of activity was impaired, whereas the group who were using the valve did not. In the long-term the valve was cheaper and caused less morbidity, but because it is constructed to allow one-way flow, this was not associated with an increase in the incidence of urinary tract infections.

Adult↗
PubMed1997

Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population.

Most multiple case families of young onset breast cancer and ovarian cancer are thought to be due to highly penetrant mutations in the predisposing genes BRCA1 and BRCA2. However, these mutations are uncommon in the population and they probably account for only a few percent of all breast cancer incidence. A much larger fraction of breast cancer might, in principle, be due to common variants which confer more modest individual risks. There are several common polymorphisms in the BRCA1 gene which generate amino acid substitutions. We have examined the frequency of four of these polymorphisms: Gln356Arg, Pro871Leu, Glu1038Gly and Ser1613Gly in large series of breast and ovarian cancer cases and matched controls. Due to strong linkage disequilibrium, these four sites generate only three haplotypes with a frequency > 1.3%. The most common haplotypes, defined by the alleles Gln356Pro871Glu1038Ser1613 and Gln356Leu871Gly1038Gly1613, have frequencies of 0.57 and 0.32 respectively, and these frequencies do not differ significantly between patient and control groups. Thus the most common polymorphisms of the BRCA1 gene do not make a significant contribution to breast or ovarian cancer risk. However, our data suggest that the Arg356 allele may have a different genotype distribution in breast cancer patients from that in controls (Arg356 homozygotes are more frequent in the control groups, P = 0.01), indicating that it may be protective against breast cancer. If this finding can be confirmed, it may provide an insight into the structural features of the BRCA1 protein that are important for its function.

Adult↗
PubMed1997

Management of the later complications of severe acute pancreatitis - pseudocyst, abscess and fistula.

The first-line management of the later complications of severe acute pancreatitis has moved increasingly towards a non-operative approach. Asymptomatic pseudocysts may be safely observed while awaiting spontaneous resolution. Symptomatic, enlarging or complicated pseudocysts, particularly those with an immature wall, should be treated by percutaneous catheter drainage (PCD), reserving surgical drainage for treatment failures. Pancreatic abscesses, if coexisting necrosis can be confidently excluded, should respond to PCD or, if this fails, surgical external drainage. Pancreatic fistulas are rare and often respond to conservative measures. Endoscopically placed pancreatic ductal stents may allow the duct disruption to heal and avoid the need for surgical intervention.

Abscess↗
PubMed1997

A developmentally regulated MAP kinase activated by hydration in tobacco pollen.

A novel mitogen-activated protein (MAP) kinase signaling pathway has been identified in tobacco. This pathway is developmentally regulated during pollen maturation and is activated by hydration during pollen germination. Analysis of different stages of pollen development showed that transcriptional and translational induction of MAP kinase synthesis occurs at the mid-bicellular stage of pollen maturation. However, the MAP kinase is stored in an inactive form in the mature, dry pollen grain. Kinase activation is very rapid after hydration of the dry pollen, peaking at approximately 5 min and decreasing thereafter. Immunoprecipitation of the kinase activity by an anti-phosphotyrosine antibody is consistent with the activation of a MAP kinase. The kinetics of activation suggest that the MAP kinase plays a role in the activation of the pollen grain after hydration rather than in pollen tube growth.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1997

Co-induction and laryngeal mask insertion. A comparison of thiopentone versus propofol.

Conditions for insertion of the laryngeal mask airway were assessed in 70 unpremedicated patients comparing the co-induction with midazolam-alfentanil-thiopentone and midazolam-alfentanil-propofol. Following pre-induction doses of midazolam 0.04 mg.kg-1 and alfentanil 10 micrograms.kg-1, patients received equipotent doses of either thiopentone or propofol. Whilst jaw relaxation and ease of laryngeal mask insertion were similar between the two groups, patients receiving propofol were less likely to have undesired responses requiring additional boluses of induction agent (p < 0.05). We conclude that, using these doses, propofol is superior to thiopentone for laryngeal mask airway insertion when using a co-induction technique.

Adolescent↗
PubMed1997

Improving the detection rate of early gastric cancer requires more than open access gastroscopy: a five year study.

BACKGROUND/AIMS: To explore the reasons why patients with gastric cancer continue to present with advanced disease despite open access gastroscopy. PATIENTS: All patients diagnosed with gastric cancer between 1 August 1989 and 31 July 1994. METHODS: A retrospective study of the presentation of gastric cancer in South Tees; patients were diagnosed at open access gastroscopy or referred through conventional channels. Primary care records of 81 patients dying between 1991 and 1995 were analysed for previous symptoms, investigations, and antisecretory drug therapy. Findings were compared with 200 age and sex matched controls. RESULTS: The overall incidence of earlier stage gastric cancer remains low at 13%. Diagnostic delay occurs in both primary and secondary care due to a high incidence of previous dyspepsia and investigation. One in six patients had been previously investigated in the three years prior to diagnosis, the majority of whom were on antisecretory drugs. CONCLUSIONS: Early gastric cancer remains rare in South Tees health district. Advantages of open access gastroscopy appear to be compromised by delayed referral to hospital and failure of endoscopists to recognise the early disease; either they are unaware of its appearance or prior treatment with an H2 receptor antagonist masks the disease by allowing mucosal healing.

Aged↗
PubMed1997

Migratory abilities of different vascular cells from the tunica media of canine vessels.

In response to injury, vascular smooth muscle cells (VSMC) are thought to migrate toward the area of damage, where they participate in the reparative process. We have recently identified and isolated two distinct cell types (VSMC and type 2 cells) from the tunica media of canine carotid artery and saphenous vein. The purpose of these experiments was to determine whether both cell types were able to migrate in response to a variety of chemoattractants. A multiwell Boyden chamber and a wound migration assay were used to assess the migratory ability of these cells in vitro. The results indicated that VSMC did not exhibit directed migration in response to either 10% fetal bovine serum or platelet-derived growth factor (PDGF)-AB. In contrast, type 2 cells migrated to serum, PDGF-AB, and PDGF-BB but not to PDGF-AA, endothelin (ET)-1, or ET-3. No difference in migratory ability was detected between type 2 cells isolated from carotid arteries or saphenous veins. It is concluded that the migratory ability of cells within the tunica media of vessels from adult animals are not equal, suggesting that only selected cells may participate in vascular wall repair.

Animals↗
PubMed1997

Bovine spongiform encephalopathy: is it an autoimmune disease due to bacteria showing molecular mimicry with brain antigens?

Bovine spongiform encephalopathy (BSE) could be an autoimmune disease produced following exposure of cattle to feedstuffs containing bacteria showing molecular mimicry between bacterial components and bovine tissue. Analysis of molecular sequence databases (Genbank and SwissProt) shows that three bacteria (Acinetobacter calcoaceticus,Ruminococcus albus, and Agrobacter tumefaciens) share sequences with the encephalitogenic peptide of bovine myelin, while three molecules in Escherichia coli show molecular mimicry with host-encoded prion protein. Immune responses against these bacteria at both T and B cell levels may cause neurological tissue injury resembling BSE. The role of these bacteria in BSE, if any, merits further investigation.

Animal Feed↗
PubMed1997

Antibodies to Klebsiella, Proteus, and HLA-B27 peptides in Japanese patients with ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVE: To determine whether patients with ankylosing spondylitis (AS) and patients with rheumatoid arthritis (RA) from Japan have antibodies to Klebsiella pneumoniae and Proteus mirabilis and to assess whether such antibodies are activated against peptides sharing sequences with HLA-B27. METHODS: Serum samples from 152 Japanese patients, 52 with AS, 50 with RA, and 50 healthy controls, were tested against 3 bacteria (K. pneumoniae, P. mirabilis, and Escherichia coli) and 3 synthetic peptides (HLA-B27, pullulanase-D, and scrambled pullulanase-D control peptide) by ELISA under coded conditions. Samples were tested for elevations in IgG, IgA, and IgM antibody classes in patients with active AS or RA, in patients with RA with probable disease, and in patients with inactive AS. Disease activity was determined by an elevated serum C-reactive protein (> 10 mg/l) level and elevated erythrocyte sedimentation rate (> 20 mm/h). RESULTS: Patients with active AS showed specific elevations in serum IgA antibody levels against K. pneumoniae compared to patients with RA and controls (p < 0.001). No such elevation was seen in the IgG and IgM antibody classes. Patients with inactive AS showed no elevation in any class of antibody against K. pneumoniae compared to controls or patients with RA. Patients with active or probably active RA showed significant elevations in IgG antibody levels against P. mirabilis compared to AS and controls (p < 0.001). Patients with AS (active or inactive), RA (active or probably active), and controls showed no elevations in any antibody class to E. coli. Both active and inactive AS patients had specific autoantibodies against HLA-B27 peptide compared to patients with RA and controls (active AS: IgG, IgA, IgM, p < 0.001; inactive AS: IgG and IgA, p < 0.001). Patients with active AS had IgG and IgA antibodies against pullulanase-D peptide, which contains a sequence that cross reacts with HLA-B27 compared to controls (p < 0.001). CONCLUSION: These results provide the first evidence of AS and RA patients in Japan having specific elevations of antibody to K. pneumoniae and P. mirabilis, respectively. This suggests that K. pneumoniae in AS and P. mirabilis in RA may play a role in triggering and/or exacerbating these diseases.

Adult↗
PubMed1997

Nonstriatal dopamine D1 receptors regulate striatal acetylcholine release in vivo.

The role of dopamine (DA) D1 receptors in the regulation of acetylcholine (ACh) release in the striatum was studied using in vivo microdialysis in freely moving rats. Systemic administration of the full D1 DA receptor agonist A-77636 (4 micromol/kg) increased striatal ACh release by 53% above the base line and decreased DA release by 33%. Local application of A-77636 (10 and 100 microM) by reverse dialysis was without effect on either striatal ACh or DA release. Systemic administration of the D1 DA receptor antagonist SCH 23390 (0.74 micromol/kg) or SCH 39166 (1.42 micromol/kg) blocked the stimulation of striatal ACh release produced by systemic A-77636 (4 micromol/kg). Local perfusion of either SCH 23390 or SCH 39166 did not decrease basal ACh release. Furthermore, when applied locally via the dialysis probe, SCH 23390 (12 microM) or SCH 39166 (50 microM) failed to attenuate the stimulation of striatal ACh release produced by systemic A-77636. Similarly, d-amphetamine (5.42 micromol/kg)-induced increases in striatal ACh release were not modified by simultaneous local perfusion with SCH 39166 (50 microM). These findings are consistent with the hypothesis that D1 receptor activation stimulates ACh release in the striatum. However, because local application of D1 receptor agonists and antagonists fail to influence ACh release, the relevant D1 receptors are not located in the striatum. The use of unphysiological dialysis conditions (high concentrations of acetylcholinesterase (AChE) inhibitors, high Ca++ concentrations and an absence of Mg++ in the perfusion fluid) may account for some earlier suggestions that local D1 receptors regulate ACh release in the striatum.

Acetylcholine↗
PubMed1997

The role of interleukin-2, interleukin-12, and dendritic cells in cancer therapy.

PURPOSE: Recombinant interleukin-2 (rIL-2) administration can mediate regression of solid tumors in patients with melanoma and renal cell carcinoma. A better understanding of the mechanisms of rIL-2-mediated antitumor effects has led to the investigation of novel immunotherapeutic approaches. Two approaches that appear promising include administration of antigen-pulsed dendritic cells (DC) and administration of DC or genetically engineered fibroblasts expressing human interleukin-12 (IL-12). The rationale for these immunotherapeutic approaches and preliminary clinical studies are presented. PATIENTS AND METHODS: We have conducted a pilot study to evaluate the feasibility of treating melanoma patients with peptide-pulsed DC. Six melanoma patients received 1 to 3 x 10(6) DC pulsed with synthetic melanoma antigenic peptides. The peptide-pulsed DC were infused weekly for 4 weeks. We have also treated 32 patients in a phase I/II trial with IL-12-producing fibroblasts. Patients received escalating doses of cells weekly for 4 weeks, which produced quantities of IL-12 ranging from 10 ng to 9 micrograms/24 hours. RESULTS: Infusion of melanoma peptide-pulsed DC produced a complete response in one patient, and significant T-cell and DC infiltration of melanoma lesions was observed. Lesional and regional responses have been observed in patients with melanoma, head and neck carcinoma, and breast cancer who received intralesional injections of IL-12-producing fibroblasts. Phase II studies of this approach are planned and will be initiated in the next few months. CONCLUSIONS: These studies confirm the feasibility of these novel immunotherapeutic approaches and demonstrate their potential antitumor activity. These approaches may be effective in patients with metastatic melanoma and other solid tumors, and they may ultimately be used to improve the efficacy of rIL-2-based immunotherapy.

Carcinoma, Renal Cell↗
PubMed1997

Evaluation of three rapid RNA extraction reagents: relevance for use in RT-PCR's and measurement of low level gene expression in clinical samples.

Although peripheral blood and bone marrow are usually readily available from patients, present techniques of RNA extraction are tedious, require millilitres of starting material and removal of red blood cells before RNA purification. Further, successful reverse transcriptase polymerase chain reaction (RT-PCR) amplification requires the removal of haemoglobin derivatives which interfere with the PCR process. Recently, one step rapid use reagents have become available, claiming to be useful for obtaining high quality RNA from microlitre quantities of whole blood drawn directly from the patient. Their use to date in clinical samples appears limited with little information in the literature documented. In an attempt to overcome this, we tested the Trizol-LS, RNA-STAT-50 and Ultraspec-3 reagents upon a statistically significant number of clinical isolates of fresh and cryopreserved peripheral blood, bone marrow, blood apheresis products and a breast cancer cell line (MCF7) in order to evaluate whether these methods could be applied to routine laboratory use in an RT-PCR method capable of detecting rare gene expression. Our findings showed that there was some variation in the quality of RNA extracted which was indicated by absorbance spectrophotometry at 260 and 280 nm. 1% agarose gel electrophoresis showed that each of these methods could yield total RNA capable of generating the signature 18S and 28S rRNA bands. Using the Kruskal-Wallis non-parametric anova test combined with Dunn's multiple comparison test, the only statistically significant difference (p<0.05) indicated that Trizol-LS was more reliable than RNA-STAT-50-LS and Ultraspec-3 at extracting RNA from fresh peripheral blood. RNA extracted with the Trizol-LS and RNA STAT-50 reagents was successfully amplified in a multiplex RT-PCR reaction for detection of the multi-drug resistance related genes MDR1, the multi-drug resistance related protein (MRP) and topoisomerase IIalpha. Low level MDR1 gene expression could be detected in frozen whole blood. However, PCR products were only seen when the anti-coagulant heparin was removed from all samples prior to cDNA production. RT-PCR amplification was not 100% successful with RNA extracted with Ultraspec-3 reagent. In conclusion, we found that the RNA extracted from whole blood with the Trizol-LS and the RNA-STAT-50 are suitable for use in clinically relevant molecular biology protocols that analyze rare event genes without further purification. Our results indicated that the Trizol-LS reagent was generally more consistent in obtaining a pure and sufficient quantity of RNA from patient material as shown by the mean result of purity and quantity in comparison to either Ultraspec-3 or RNA-STAT-50-LS reagents. Ultraspec-3 is not easily suited for direct use with whole blood products.

Evaluation Studies as Topic↗
PubMed1996

Diastereoselective synthesis of all four isomers of 3-(4-chlorophenyl) glutamic acid: identification of the isomers responsible for the potentiation of L-homocysteic acid-evoked depolarizations in neonatal rat motoneurons.

All four isomers of 3-(4-chlorophenyl)glutamic acid (5-8) were prepared by diastereoselective synthesis. Addition of (6S)-(+)-bis-lactim ether 15 to cis-4-chlorocinnamate 12 gave a mixture comprising mainly the (2R,3S)- and (2R,3R)-isomers 5 and 6, respectively (in a ratio of 56:40), while addition of (6R)-(-)-bis-lactim ether 16 to 4-chlorocinnamate 12 gave a mixture comprising mainly the (2S,3R)- and (2S,3S)-isomers 8 and 7, respectively (in a ratio of 56:42). The four stereoisomers (5-8) were therefore conveniently prepared by addition of either 3-lithio-(6S)- or -(6R)-bis-lactim ether (15 or 16, respectively) to 4-chlorocinnamate 12 and separation of the resultant mixtures of diastereoisomers (23-26) by flash silica gel chromatography. The absolute configurations of 6 and 7 were confirmed by X-ray crystallography. Both the (2S,3S)- and (2S,3R)-isomers (7 and 8, respectively) at a concentration of 100 microM significantly potentiated depolarizations induced by 10 microM L-homocysteic acid (L-HCA) (% control +/- sem: 130.4 +/- 3.6, n = 20 and 114.5 +/- 2.4, n = 11, respectively) while the (2R,3S)-isomer 5 significantly reduced L-HCA response amplitude (94.2 +/- 1.4, n = 9) and the (2R,3R)-isomer 6 was inactive. Experiments designed to compare the agonist-potentiating actions of 7 and 8 in the neonatal rat spinal cord with L-trans-pyrrolidine-2,4-dicarboxylic acid, the well-known L-Glu uptake inhibitor, provided additional evidence for the selective enhancement of depolarizations due to L-HCA and not those due to L-Glu. This selective action supports the existence of multiple excitatory amino acid uptake sites.

Animals↗
PubMed1996

A JNK signal transduction pathway that mediates morphogenesis and an immune response in Drosophila.

The Drosophila MAP kinase DJNK is a homolog of the mammalian c-Jun amino-terminal kinase (JNK). Mutations in the DJNK gene correspond to the complementation group basket. DJNK is phosphorylated and activated by the Drosophila MAP kinase kinase HEP. Substrates of DJNK include the transcription factor DJun. DJNK participates in multiple physiological processes. Exposure to endotoxic lipopolysaccharide initiates an insect immune response and leads to DJNK activation. In addition, embryos lacking DJNK are defective in dorsal closure, a process in which the lateral epithelial cells migrate over the embryo and join at the dorsal midline. These data demonstrate that the DJNK signal transduction pathway mediates an immune response and morphogenesis in vivo.

Alleles↗