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Biomedical subjects

C Wilson

Publications and source records attributed to C Wilson.

At least 217 records · Page 12Linked to original sources
PubMed1997

Inhibition of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumor growth by aryl hydrocarbon receptor agonists.

The antitumorigenic activities of 6-methyl-1,3,8-trichlorodibenzofuran (6-MCDF), 8-methyl-1,3,6-trichlorodibenzofuran (8-MCDF) and 6-cyclohexyl-1,3,8-trichlorodibenzofuran (6-CHDF) were investigated in the 7,12-dimethylbenz[a]anthracene (DMBA) rat mammary tumor model. At doses of 5, 10 or 25 mg/kg/week, both 6-MCDF and 8-MCDF significantly inhibited mammary tumor growth and at the 5 mg/kg/week dose >50% growth inhibition was observed. In contrast, 6-CHDF was inactive at the 5 mg/kg/week dose and the structure-antitumorigenicity relationships (6-MCDF/8-MCDF > 6-CHDF) correlated with structure-antiestrogenicity (rat uterus) studies and the relative binding affinities of these compounds for the aryl hydrocarbon receptor (AhR). The antitumorigenic activity of 6-MCDF or 8-MCDF in the mammary was not accompanied by any significant changes in liver/body weight ratios, liver morphology or induction of hepatic CYP1A1-dependent activity which is one of the most sensitive indicators of exposure to AhR agonists. RT-PCR and Western blot analysis of mammary tumor mRNA and protein extracts, respectively, confirmed the presence of AhR suggesting that AhR-mediated signaling pathways are functional in rat mammary tumors. These results define a relatively non-toxic group of AhR agonists which exhibit potent antitumorigenic activity in the DMBA-induced rat mammary tumor model (<1 mg/kg/day), and therefore represent a new class of indirect-acting antiestrogens which have potential for clinical treatment of mammary cancer.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Cultured blood dendritic cells retain HIV-1 antigen-presenting capacity for memory CTL during progressive HIV-1 infection.

Dendritic cells (DC) are potent APC that may be involved in the pathogenesis of HIV-1 infection. We studied the APC function of DC from HIV-1-infected subjects that were derived from monocyte-depleted PBMC by culture in human IL-4 and human granulocyte-macrophage CSF. The cultured cells from the HIV-1-infected subjects had similar morphology and phenotype of mature DC (CD80 = 41 +/- 8%, CD86 = 77 +/- 5%, CD40 = 87 +/- 6%, CD1a = 1 +/- 1%) to DC cultured from seronegative subjects. The yield of these DC was lower than from HIV-1-seronegative subjects (4 +/- 0% vs 11 +/- 2%, p < 0.01), and the lower DC yields correlated with lower numbers of blood CD4+ T cells (r = 0.60, p < 0.01) and higher plasma viral load (r = -0.49, p < 0.01). DC from HIV-1-infected subjects were infected with recombinant vaccinia virus vectors expressing Gag, Pol, and Env and were able to stimulate equal or higher levels of MHC class I-restricted, anti-HIV-1 memory CTL (CTLm) than were similarly treated, autologous B lymphocyte cell lines. DC pulsed with peptides representing HIV-1 CTL epitopes stimulated higher levels of anti-HIV-1 CTLm responses than did DC infected with the vaccinia virus-HIV-1 constructs. Allogeneic, MHC class I-matched DC also stimulated anti-HIV-1 CTLm activity in cells from HIV-1-infected subjects. DC from early and late stages of HIV-1 infection had a similar ability to activate CTLm specific for targets expressing either HIV-1 genes via vaccinia virus vectors or HIV-1 immunodominant synthetic peptides. However, DC from either early or late stages of HIV-1 infection could not overcome the defect in anti-HIV-1 CTLm response in advanced infection.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Ketoacidosis in Apache Indians with non-insulin-dependent diabetes mellitus.

BACKGROUND: Although more classically associated with insulin-dependent diabetes mellitus, diabetic ketoacidosis (DKA) can occur in some patients with non-insulin-dependent diabetes mellitus (NIDDM). To better define the clinical features that may be associated with ketoacidosis in patients with NIDDM, we reviewed the medical histories of Apache Indians with NIDDM who had been treated for an episode of DKA. METHODS: Cases of ketoacidosis among patients with NIDDM were identified at 2 separate Apache Indian reservations. Chart data were used to confirm and characterize the diagnosis of NIDDM, the metabolic disturbances associated with DKA, and the historical features of the patients. RESULTS: Among 724 patients with NIDDM, 17 patients experiencing at least 1 episode of DKA were identified. The mean (+/-SD) age at the time of the episode was 40.8 +/- 13.9 years. The patients were predominantly male (15[88%]), with a mean (+/-SD) body mass index (calculated as the weight in kilograms divided by the square of the height in meters) of 24.9 +/- 4.4 kg/m2. Causes of DKA included infections (8[47%]) and omission of treatment (3/15[20%]). Concurrent abuse of alcohol was noted in 4 (27%) of the patients. In addition, a lifetime history of alcohol abuse was noted in 15 (94%) of 16 patients. CONCLUSIONS: This report confirms the growing recognition that DKA occurs in some patients with NIDDM. The present study also adds male sex, alcohol abuse, and relatively low body mass index as clinical factors that may play a role in the development of DKA in this setting.

Adult↗
PubMed1997

Absolute configuration of (+)-alpha-methyl-4-carboxyphenylglycine (MCPG), a metabotropic glutamate receptor antagonist.

The title compound, (+)-MCPG [(+)-alpha-(4-carboxyphenyl)-alpha-methylglycine, C10H11NO4], is an antagonist at certain subtypes of metabotropic glutamate (mGlu) receptors. (+)-MCPG has gained widespread acceptance as a tool for probing the physiological role of mGlu receptors in the central nervous system. As a result, mGlu receptors are now known to be involved in processes connected with learning and memory, modulation of synaptic transmission and the transmission of pain responses. (+)-MCPG crystallized in its zwitterionic form. Its absolute configuration was assigned as S from X-ray diffraction data collected at 150 K. The refined Flack parameter is consistent with this assignment, although the large e.s.d. associated with it introduces some ambiguity.

Benzoates↗
PubMed1997

Region 1 of sigma70 is required for efficient isomerization and initiation of transcription by Escherichia coli RNA polymerase.

The sigma (sigma) subunit of prokaryotic RNA polymerase is essential for promoter recognition. sigma Factor directs the RNA polymerase core subunits (alpha2beta beta') to the promoter consensus elements and thereby confers selectivity for transcription initiation. The N-terminal domain (region 1.1) of Escherichia coli sigma70 has been shown to inhibit DNA binding by the C-terminal DNA recognition domains. Since DNA recognition is the first step of transcription initiation, we predicted that the N-terminal domain of sigma70 may also influence the initiation of transcription by holoenzyme (alpha2beta beta'sigma). N-terminally truncated sigma70 derivatives were used to reconstitute holoenzyme, and transcription by the mutant holoenzymes was analyzed in vitro. Deletion of the first 75 to 100 amino acids of sigma70 (region 1.1) resulted in both a slow rate of transition from a closed promoter complex to a DNA- strand-separated open complex, as well as a reduced efficiency of transition from the open complex to a ternary initiated complex. These effects were partially reversed by the addition of a polypeptide containing region 1.1 in trans. Therefore, region 1.1 not only modulates DNA binding but is important for efficient transcription initiation, once a closed complex has formed. A deletion of the first 133 amino acids, which removes regions 1.1 and 1.2, resulted in arrest of initiation at the earliest closed complex, suggesting that region 1.2 is required for open complex formation.

Amino Acid Sequence↗
PubMed1997

New non-peptide endothelin-A receptor antagonists: synthesis, biological properties, and structure-activity relationships of 5-(dimethylamino)-N-pyridyl-,-N-pyrimidinyl-,-N-pyridazinyl-, and -N-pyrazinyl-1-naphthalenesulfonamides.

Use of automated synthesis led to the discovery of several 6-membered nitrogen heterocycles as replacements for the N-isoxazolyl substituent present in the 1-naphthalenesulfonamides endothelin-A (ETA) antagonist 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesu lfo namides (BMS 182874). In each of these heterocycles, a small substituent such as halogen para to the position of attachment to the sulfonamide nitrogen atom was found to be advantageous for ETA receptor affinity. Of these heterocycles, 2-pyrazines offered the greatest scope for improving receptor affinity. Optimization of the substituents at the 3- and 5-positions in the pyrazine ring led to potent, ETA-selective compounds such as 5-(dimethylamino)-N-(5-chloro-3-methoxy-2-pyrazinyl)-1- naphthalenesulfonamides (7m, ETA pIC50 8.1). When dosed orally at 10 mg/kg to conscious, normotensive rats infused with big ET-1, compounds such as 7m showed significant inhibition of the pressor response with a duration of effect lasting for the 5-h course of the experiment.

Animals↗
PubMed1997

Role REVersal: understanding how RRE RNA binds its peptide ligand.

The structure of a complex between the HIV Revresponsive element (RRE) RNA and a fragment of the Rev protein has recently been determined by NMR. Together with previous studies of the Tat-TAR complex, these results show how RNA elements with considerable tertiary structure are able to play a more active role in directing binding to elements of protein secondary structure.

Bacterial Proteins↗
PubMed1997

Correlation between anti-Proteus antibodies and isolation rates of P. mirabilis in rheumatoid arthritis.

In a survey of 89 RA patients, carried out under code, Proteus mirabilis was isolated from the urine of 63% (47/75) of female (P < 0.001) and 50% (7/14) of male patients (P < 0.001), compared to a frequency of isolation in healthy women of 32% (38/119) and 11% (13/115) in healthy men. There was no significant difference in isolation rates between 37 non-RA patients and healthy controls. Sera from 20 patients with RA and 20 healthy controls were tested against P. mirabilis and Escherichia coli by an enzyme-linked immunosorbent assay. Antibodies against P. mirabilis but not to E. coli were significantly higher in the RA patients than in healthy controls (P < 0.001). Furthermore, a positive correlation was found between high anti-Proteus antibody levels in serum samples and the number of Proteus colony-forming units obtained from urine specimens of the 20 RA patients (r = +0.714, P < 0.001). These results support the suggestion of an aetiopathogenic role for P. mirabilis in RA.

Adult↗
PubMed1997

Antibody responses to gut bacteria in ankylosing spondylitis, rheumatoid arthritis, Crohn's disease and ulcerative colitis.

Specific immunoreactive anti-Klebsiella antibodies are found in patients with ankylosing spondylitis (AS), a significant proportion of whom have occult inflammatory bowel disease. Molecular mimicry between Klebsiella or other bacterial antigens and HLA-B27 has been suggested in the pathogenesis of AS. The specificity of increased immunoreactivity against Klebsiella remains to be assessed against the abundant anaerobic bacterial flora, present either in healthy controls or in patients with ulcerative colitis (UC) and Crohn's disease (CD). Total immunoglobulin (Ig; IgG, IgA, IgM) immunoreactivity was measured by ELISA against Klebsiella pneumoniae, Proteus mirabilis, Escherichia coli and ten anaerobic isolates of the predominant normal bowel flora in 35 patients with active AS, 60 patients with inflammatory bowel disease (30 CD, 30 UC), 60 patients with active rheumatoid arthritis (RA) and 60 healthy controls. Ig immunoreactivity to K. pneumoniae was significantly elevated in AS (P < 0.001), CD (P < 0.001) and UC (P < 0.001) patients compared with RA patients and healthy controls. Furthermore, Ig immunoreactivity to P. mirabilis was significantly elevated only in RA patients, compared with the other inflammatory groups (P < 0.001) and controls (P < 0.001). There was no significant antibody response against E. coli or the ten obligate anaerobes in any of the test groups. The data suggested an increased immune response to Klebsiella in patients with AS, UC, CD and to Proteus in patients with RA. The specificity of these responses in some patients supported a possible role for enteric Klebsiella in the pathogenesis of AS and Proteus in RA. The role of Klebsiella in inflammatory bowel disease requires further study.

Adult↗
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↗