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Biomedical subjects

C Wilson

Publications and source records attributed to C Wilson.

At least 199 records · Page 11Linked to original sources
PubMed1998

Effect of smoking on ovarian reserve and ovarian stimulation in in-vitro fertilization and embryo transfer.

The effect of cigarette smoking on ovarian reserve as measured by basal serum follicle stimulating hormone (FSH) concentrations, and by the response to a standard ovarian stimulation protocol, was examined retrospectively in 173 consecutive women (108 non-smokers and 65 smokers) undergoing in-vitro fertilization (IVF) and embryo transfer treatment. Women who smoked had a higher mean basal serum FSH concentration (P < or = 0.0001), in particular younger (<36 years) women, and required a statistically significantly higher mean dosage of gonadotrophins for ovarian stimulation than the non-smokers (48.1 +/- 15.6 versus 38.9 +/- 13.6 ampoules, 75 IU/ampoule; P < 0.0001). A lower mean number of oocytes was obtained in smokers than non-smokers (6.2 +/- 3.4 versus 11.1 +/- 6.3, oocytes P < or = 0.0001) and the rate of abandoned cycles (18.5 versus 8.5%) and total fertilization failure (18.5 versus 8.5%) was higher. The clinical pregnancy rate per cycle in smokers was 16.9% versus 21.3% in non-smokers but this was not statistically significant. In conclusion, cigarette smoking in women appears to significantly reduce their ovarian reserve and lead to poor response to ovarian stimulation at an earlier age.

Adult↗
PubMed1998

Antibodies to Klebsiella pneumoniae lipopolysaccharide in patients with ankylosing spondylitis.

The role of microbial lipopolysaccharides (LPS) in the aetiopathogenesis of ankylosing spondylitis (AS) is a matter of continuing debate. In this study, class-specific IgG, IgA and IgM antibodies against Klebsiella pneumoniae, Escherichia coli, Salmonella typhimurium and Salmonella enteritidis LPS were measured by enzyme-linked immunosorbent assay (ELISA) in 100 AS patients, 50 rheumatoid arthritis (RA) patients and 50 healthy control subjects. The AS patients had significantly elevated levels of IgG and IgA antibodies against K. pneumoniae LPS (P < 0.001) and IgA antibodies against E. coli LPS (P < 0.05) compared to healthy controls. There were no significant elevations of antibody levels against S. typhimurium and S. enteritidis in the three study groups. In addition, there was a correlation between IgG and IgA anti-K. pneumoniae LPS antibody levels and the acute-phase reactant C-reactive protein (P < 0.001).

Adult↗
PubMed1998

Characterization of the humoral immune response to Klebsiella species in inflammatory bowel disease and ankylosing spondylitis.

This study was carried out to characterize the antibody class response by ELISA to seven Klebsiella pneumoniae serotypes (K2, K3, K17, K21, K26, K36, K50) in five different groups, 40 HLA-B27-positive ankylosing spondylitis (AS) patients, 46 patients with Crohn's disease (CD), 38 patients with ulcerative colitis (UC), 50 patients with active anti-endomysial antibody-positive coeliac disease and 40 healthy controls, using whole bacteria and capsular polysaccharide. IgG antibody levels were significantly elevated in AS patients to K17, K36, K50; IgA to K2, K3, K21, K26, K36 and K50; and IgM to serotype K21 when compared to normal controls. Furthermore, IgG antibody levels were significantly elevated in CD patients to K2, K17, K21, K26, K36 and K50; IgA to K2, K3, K21, K26, K36 and K50; and IgM to K2, K3, K17, K21 and K50. Increased IgG antibody levels in the UC group were limited only to K17, K36 and K50. No antibody class was increased to any of the K. pneumoniae serotypes in the coeliac disease group. The immune responses in AS patients also involve Klebsiella bacteria having capsular serotypes other than K26, K36 and K50. The similarity in the immune responses between CD and AS groups suggests that many AS patients may have occult bowel inflammation.

Adolescent↗
PubMed1998

Predictors of lean body mass and total adipose mass in community-dwelling elderly men and women.

As part of an ongoing longitudinal study, we analyzed cross-sectional data to identify the predictors of lean body mass (LBM) and total adipose mass (TAM) in community-dwelling elderly men and women. Body composition analysis was done using dual energy x-ray absorptiometry. A total 262 subjects (118 women and 144 men), 60 to 80 years of age, from the urban and suburban communities of southeastern Wisconsin were studied. In women, the age (r = -.18), body mass index (BMI) (r = .43), and waist-to-hip ratio (WHR) (r = .30), and in men, BMI (r = .45) and insulin-like growth factor-1 (IGF-1) (r = .32) were identified as predictors (P < .05) of LBM. In women, the BMI (r = .87), WHR (r = .21), and functional work capacity (VO2 max) (r = -.47), and in men, the BMI (r = .83), WHR (r = .52), dehydroepiandrosterone sulfate (DHEAS) (r = -.27), total testosterone (TT) (r = -.35), free testosterone (FT) (r = -.23), physical activity (LTE) (r = -.32), and VO2 peak (r = -.59) were identified as predictors of TAM. After partialling out age in addition to the predictors identified earlier, the VO2 peak was identified as a predictor (P < .05) of LBM in both women and men, and TT, FT, and LTE as predictors (P < .05) of LBM in men. We conclude that the BMI, WHR, and VO2 peak influences LBM and TAM in both women and men. Additionally, in men LBM and TAM is influenced by hormone profile.

Absorptiometry, Photon↗
PubMed1998

A role for noradrenaline in pre-eclampsia: towards a unifying hypothesis for the pathophysiology.

OBJECTIVE: To compare plasma catecholamine (noradrenaline and adrenaline) levels in pre-eclamptic to normotensive pregnancy, and to study the activity of synthetic enzymes for catecholamines in placental and trophoblastic cell cultures. We postulated that catecholamines might be an important signal secreted by the fetoplacental unit in pre-eclampsia. METHODS: We recruited 12 women with pre-eclampsia and 12 pregnant women with nonproteinuric hypertension undergoing delivery by caesarean section, 23 normotensive women undergoing elective caesarean section at term, and 26 normotensive primigravid women with ongoing pregnancies at gestations equivalent to those women with pre-eclampsia. We measured venous blood concentrations of catecholamines. Following delivery, we studied tyrosine hydroxylase (the rate limiting enzyme for catecholamine synthesis) activity in placental tissue of these women as well as from four eclamptic women not in the observer study. We used Northern blot analysis to quantify mRNA for tyrosine hydroxylase and dopamine-beta-hydroxylase (D-beta-H, a non-rate-limiting synthetic enzyme for catecholamine) in placental tissue, as well as in trophoblast cells in primary culture and trophoblast cell lines. RESULTS: Venous blood concentrations of noradrenaline were significantly higher in pre-eclamptic women compared with normotensive women. Tyrosine hydroxylase activity was greater in placental tissue from pre-eclamptic and eclamptic compared with normotensive pregnancies, as were mRNA levels for this enzyme. The mRNA levels for the non-rate-limiting D-beta-H in women with pre-eclampsia were similar to those in normotensive pregnancies. First trimester trophoblast cells in primary culture and trophoblast cell lines transcript mRNA for tyrosine hydroxylase and D-beta-H. CONCLUSIONS: Trophoblasts have the capacity to secrete catecholamines, and we found increased activity of the rate-limiting synthetic enzyme in placental tissue from pre-eclamptic pregnancies. We postulate that the higher levels of catecholamines we found in the plasma of women with pre-eclampsia might be of placental origin. We hypothesise that in pre-eclampsia ischaemic trophoblast tissue secretes catecholamines as a physiological signal to increase maternal blood flow to the fetoplacental unit, which itself is spared the vasoconstrictor effects of catecholamines (placental vessels are known to be unresponsive to catecholamines). However, since the basic pathology--defective trophoblast invasion--is not corrected, the increased blood flow fails to resolve the ischaemia, and the secretion of catecholamines is therefore sustained or even enhanced. Noradrenaline is known to cause lipolysis. This results in breakdown of triglycerides to free fatty acids, which are oxidized to lipid peroxides. The latter are cytotoxic and cause widespread endothelial cell damage and dysfunction, culminating in the clinical syndrome of pre-eclampsia.

Adult↗
PubMed1998

Association of dehydroepiandrosterone sulfate, body composition, and physical fitness in independent community-dwelling older men and women.

OBJECTIVES: To determine the association of dehydroepiandrosterone sulfate (DHEAS), body composition, and physical fitness in independent community-dwelling men and women aged 60 to 80 years. DESIGN: Cross sectional analysis. PARTICIPANTS: Independent men and women, 60 years of age and older, living in urban and suburban communities of Southeastern Wisconsin. MEASUREMENTS: History, physical examination, physical activity level, and anthropometrics were measured for every subject. Total adipose mass (TAM) and lean body mass were measured using dual energy X-ray absorptiometry. Dehydroepiandrosterone sulfate, insulin-like growth factor-1 (IGF-1), total testosterone (TT), and free testosterone (FT) were measured using radioimmunoassay. Physical fitness was measured as VO2max using exercise stress tests. Blood for lipids was analyzed using standard assays. RESULTS: In men, the DHEAS was significantly correlated to age (r = -.32), TAM (r = -.27), percent fat (r = -.30), HDL cholesterol (r = .34), TT (r = .30), VO2max (r = .23), and percent lean body mass (% LBM) (r = .33). In women, the DHEAS was not significantly correlated to any of the variables examined except body mass index (BMI) (r = .23). In men, after partialling out age, DHEAS was significantly correlated to HDL, % fat, TAM, % LBM, and TT. Multivariate analysis for men revealed that high density lipoprotein cholesterol (HDL) was the strongest predictor of serum DHEAS level, followed by % LBM, BMI, and age. The men in the highest quartile of serum DHEAS levels were different from those in the lowest quartile in terms of age, TT, FT, % fat, TAM, % LBM, HDL, and low density lipoprotein (LDL) cholesterol level. No such differences were found in the two groups of women. CONCLUSION: In this group of independent community-dwelling older men, several factors were found to be associated with the serum DHEAS concentration, whereas in a group of older women, no such associations were identified with the exception of BMI. Men in the highest quartile of serum DHEAS level, compared with those with a serum DHEAS level in the lowest quartile, were younger, leaner, more fit, had higher TT and FT levels, and had a favorable lipid profile. No such differences were identified between the women in the highest and the lowest quartiles of serum DHEAS level.

Absorptiometry, Photon↗
PubMed1998

Inhibition of NF-kappaB activation in combination with bcl-2 expression allows for persistence of first-generation adenovirus vectors in the mouse liver.

NF-kappaB is a key regulator of the innate antiviral immune response, due in part to its transcriptional activation of cytokines and adhesion molecules, which, in turn, function in chemotaxis and activation of inflammatory cells. We reported earlier that viral gene expression in hepatocytes transduced with first-generation (E1-deleted) adenoviruses induced NF-kappaB activation, elevation of serum cytokines, and hepatocellular apoptosis during the first days postinfusion. These events did not occur in mice infused with an adenovirus vector deleted for E1, E2, E3, and late gene expression. In the present study, we used an adenovirus expressing an IkappaBalpha supersuppressor (Ad.IkappaBM) and bcl-2 transgenic mice to unravel the role of virus-induced NF-kappaB activation and apoptosis in the clearance of recombinant adenovirus vectors from the liver. The combined action of IkappaBM and Bcl-2 allowed for vector persistence in livers of C57BL/6 x C3H mice. In the absence of Bcl-2, IkappaBM expression in mouse livers significantly reduced NF-kappaB activation, cytokine expression, leukocyte infiltration, and the humoral immune response against the transgene product; however, this was not sufficient to prevent the decline of vector DNA in transduced cells. Infusion of Ad.IkappaBM caused extended apoptosis predominantly in periportal liver regions, indicating that NF-kappaB activation may protect transduced hepatocytes from apoptosis induced by adenovirus gene products. To confer vector persistence, bcl-2 transgene expression was required to block virus-induced apoptosis if NF-kappaB protection was inactivated by IkappaBM. Expression of gene products involved in early stages of apoptotic pathways was up-regulated in response to virus infusion in bcl-2 transgenic mice, which may represent a compensatory effect. Our study supports the idea that the suppression of innate defense mechanisms improves vector persistence.

Adenoviridae↗
PubMed1998

Effect of chronic fluoride exposure in uremic rats.

This study was conducted to test the hypothesis that the margin of safe fluoride exposure is narrowed in rats that are physiologically compromised by renal dysfunction. The study objective was to determine whether increases in fluoride retention and tissue fluoride levels in rats with surgically induced renal insufficiency result in toxic fluoride effects not ordinarily observed in healthy animals. Uremic and sham-operated control rats received 0 microg/ml, 5 (0.26 mmol/l), 15 (0.79), or 50 microg/ml (2.63 mmol/l) of fluoride in their drinking water for 3 or 6 months. Fluoride retention was monitored, and, following euthanasia, tissue fluoride and biochemical markers of tissue function were analyzed. Selected tissues were saved for histology, and bone marrow cells were harvested for determining the frequency of sister chromatid exchange, a marker of genetic damage. In spite of significantly higher levels of fluoride in the tissues of the animals with renal insufficiency, there were no clinically adverse, fluoride-induced, extraskeletal physiological, biochemical, or genetic effects of chronic exposure to common levels of fluoride in these rats.

Animals↗
PubMed1998

A cell cycle regulated MAP kinase with a possible role in cytokinesis in tobacco cells.

Mitogen-activated protein (MAP) kinases have been demonstrated to have a role in meiosis but their involvement in mitotic events is less clear. Using a peptide antibody raised against the tobacco MAP kinase p43(Ntf6) and extracts from synchronized tobacco cell suspension cultures, we show that this kinase is activated specifically during mitosis. Entry into mitosis appears to be necessary for the activation of the kinase, which occurs as a post-translational event. The activation of the kinase occurs in late anaphase/early telophase. The p43(Ntf6) protein shows a transient localization to the cell plate in anaphase cells, in the middle of the two microtubule arrays characteristic of the phragmoplast, a plant-specific structure involved in laying down the new cell wall. The combined data support a role for the MAP kinase p43(Ntf6) in cytokinesis in tobacco cells.

Anaphase↗
PubMed1998

Polymacron enzyme immunoassay system for detection of naturally contaminating Salmonella in foods, feeds, and environmental samples.

A simple dot blot enzyme immunoassay was developed to screen enrichment broth cultures for the presence of Salmonella. This unique system utilizes macroporous polyester cloth (Polymacron) with an inexpensive hemoglobin coating to provide a high-affinity adsorbent for lipopolysaccharide (LPS) antigens in test samples. Bound LPS antigens are then detected using a monoclonal antibody conjugate recognizing a core oligosaccharide epitope common to all salmonellae frequently found in foods and related samples. The entire test (not including enrichment culture) could be completed in less than 1 h. The performance of this assay was evaluated in the analysis of enrichment broth cultures from a variety of egg and dairy products, chicken carcasses, animal feeds, and food-processing plant environmental samples for the presence of Salmonella.

Animal Feed↗
PubMed1998

Antibodies to Klebsiella pneumoniae in Dutch patients with ankylosing spondylitis and acute anterior uveitis and to Proteus mirabilis in rheumatoid arthritis.

OBJECTIVE: To determine whether the association between increased humoral reactivity against Klebsiella and HLA-B27 associated diseases could be confirmed in Dutch patients with ankylosing spondylitis (AS) and acute anterior uveitis (AAU). METHODS: Under coded conditions sera from Dutch patients with AS, AAU, and rheumatoid arthritis (RA) and from HLA-B27 positive and negative healthy controls were studied for IgA anti-Klebsiella (K54) and IgG anti-Proteus antibodies with the indirect immunofluorescence assay on whole bacteria fixed in suspension with paraformaldehyde. Each group consisted of at least 17 sera. RESULTS: IgA anti-Klebsiella antibody titers were elevated in AS and HLA-B27 negative AAU compared to the HLA-B27 positive and negative controls or patients with active RA (p < 0.001). Furthermore, patients with active RA had elevated levels of IgG antibodies against P. mirabilis compared to every other test or control group (p < 0.001). There was no significant difference between the AS and RA patients in terms of serum C-reactive protein levels, although these were significantly elevated in both compared to healthy controls (p < 0.001), suggesting that the antibody elevations were not due to a nonspecific inflammatory effect. The same sera were blindly tested with negative results by 2 other centers. The discrepancies are probably the result of differences in the methods used. CONCLUSION: Our data support the hypothesis that Klebsiella are involved in the pathogenesis of AS and AAU and that the same might be true for Proteus in RA.

Adult↗
PubMed1998

A review of direct current cardioversions for atrial arrhythmia.

UNLABELLED: The risk of arterial embolism is well recognised following Direct Current Cardioversion (DCC) for atrial fibrillation although the use of prophylactic anticoagulation remains controversial. AIM: To determine the risk of arterial embolism post-cardioversion and which factors predict successful cardioversion and maintenance of sinus rhythm. MATERIALS AND METHODS: A retrospective study was carried out of all cardioversions performed for atrial fibrillation and atrial flutter at the Waveney Hospital Ballymena, during 1989-1993. A review of medical records and electrocardiograms was carried out to assess demographic characteristics, co-existent diseases, anticoagulant status, echocardiographic features and characteristics of the arrhythmia. Embolic events in the six weeks post-cardioversion were noted. RESULTS: The study included 157 cardioversions in 109 patients. The predominant arrhythmia was atrial fibrillation (n = 108, 69%). Three of 109 patients (2.7%) experienced embolic complications, none of whom had anticoagulation prior to the procedure. No risk factors for cerebro-vascular disease or significant valvular heart disease were present. Return to sinus rhythm was achieved in 143 (91%) procedures. Increasing coarseness of atrial fibrillation was associated with a non-significant trend towards successful restoration of sinus rhythm (p = 0.18). Recurrence of the original arrhythmia was predicted by an increase in coarseness of atrial fibrillation (p < 0.05). CONCLUSIONS: These findings indicate that embolic complications can occur in patients undergoing DCC with normal echocardiographic dimensions, and that prophylactic anticoagulation should be considered in all patients. Coarseness of atrial fibrillation may be used as a guide to predict the chance of successful cardioversion and of the likelihood of maintaining sinus rhythm once this has been achieved.

Adult↗
PubMed1998

Pharmaceutical regulation in the single European market.

This paper assesses the impact of new EU-wide drug authorisation procedures. The paper examines various attempts to introduce harmonised market authorisation routes for pharmaceuticals including the establishment of the multi-state, concentration, decentralised and centralised procedures. The paper considers the current role of the European Medicines Evaluation Agency and the likelihood that its powers will be increased in the future. Finally, the paper assesses whether EU regulation has created beneficial market conditions for pharmaceutical companies operating in the single European market.

Drug Approval↗
PubMed1997

Mutations in dihydropteroate synthase are responsible for sulfone and sulfonamide resistance in Plasmodium falciparum.

Plasmodium falciparum causes the most severe form of malaria in humans. An important class of drugs in malaria treatment is the sulfone/sulfonamide group, of which sulfadoxine is the most commonly used. The target of sulfadoxine is the enzyme dihydropteroate synthase (DHPS), and sequencing of the DHPS gene has identified amino acid differences that may be involved in the mechanism of resistance to this drug. In this study we have sequenced the DHPS gene in 10 isolates from Thailand and identified a new allele of DHPS that has a previously unidentified amino acid difference. We have expressed eight alleles of P. falciparum PPPK-DHPS in Escherichia coli and purified the functional enzymes to homogeneity. Strikingly, the Ki for sulfadoxine varies by almost three orders of magnitude from 0.14 microM for the DHPS allele from sensitive isolates to 112 microM for an enzyme expressed in a highly resistant isolate. Comparison of the Ki of different sulfonamides and the sulfone dapsone has suggested that the amino acid differences in DHPS would confer cross-resistance to these compounds. These results show that the amino acid differences in the DHPS enzyme of sulfadoxine-resistant isolates of P. falciparum are central to the mechanism of resistance to sulfones and sulfonamides.

Animals↗
PubMed1997

Studies on the relationship between estrogen receptor content, glutathione S-transferase pi expression, and induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin and drug resistance in human breast cancer cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces both phase I and phase II drug-metabolizing enzymes in rodent liver and hepatoma cell lines and this induction is mediated by the aryl hydrocarbon (Ah) receptor. Induction of CYP1A1 by TCDD in human breast cancer cells has been reported and results of several studies suggest that the estrogen receptor (ER) may be required for Ah responsiveness. This study investigates the induction of GST pi by TCDD in human breast cancer cells and the role of the ER in mediating this response. TCDD did not induce chloramphenicol acetyl transferase (CAT) activity in ER positive (ER+) MCF-7 and ER- MDA-MB-468 and MDA-MB-231 human breast cancer cell lines transiently transfected with GST pi (human) or GSTP (rat) promoter-reporter constructs containing the -291/+36 and -2.9/+59 region, respectively, of the GST pi and GSTP gene promoters. Furthermore, TCDD did not induce GST pi or GSTP in MDA-MB-468 and MDA-MB-231 human breast cancer cells stably transfected with the ER. RT-PCR confirmed that GST pi mRNA levels were low in ER+ MCF-7 cells and high in ER- MDA-MB-468 and MDA-MB-231 cells; however, in MDA-MB-468 and MDA-MB-231 cells stably transfected with the ER GST pi mRNA levels remained elevated and were not inducible. MDA-MB-468 and MDA-MB-231 cells stably transfected with the ER exhibited increased GST activity and decreased GSH content compared to wild-type cells; however, in MDA-MB-468 cells stably transfected with ER, the susceptibility to doxorubicin, ellipticine, chlorambucil, malphalan, or cisplatin was similar to that observed in wild-type cells. Adriamycin accumulation was similar in wild-type and ER stably transfected cells and verapamil did not affect this response, suggesting that ER expression did not influence p-glycoprotein activity. Taken together these data suggest that not all GST isoforms are responsive to TCDD and stable transfection of ER- cells with ER is not sufficient to restore the ER+ phenotype in some breast cancer cell lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Estrogen does not inhibit 2,3,7, 8-tetrachlorodibenzo-p-dioxin-mediated effects in MCF-7 and Hepa 1c1c7 cells.

The estrogen receptor and aryl hydrocarbon receptor (AhR) are coexpressed in several Ah and estrogen-responsive human breast cancer cell lines. However, a recent study reported that 17beta-estradiol (E2) inhibited Ah responsiveness in mouse Hepa 1c1c7 hepatoma cells (Kharat, I., and Saatcioglu, F. (1996) J. Biol. Chem. 271, 10533-10537), and therefore, estrogen receptor-AhR cross-talk was reinvestigated in MCF-7 and mouse Hepa 1c1c7 cells. Treatment of MCF-7 or Hepa 1c1c7 cells with 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in induction of CYP1A1-dependent activity and mRNA levels. Treatment of both cell lines with E2 had no effect on basal or TCDD-inducible CYP1A1-dependent activity or mRNA levels. In MCF-7 and Hepa 1c1c7 cells transiently transfected with an Ah-responsive plasmid containing the 5'-regulatory region of the human CYP1A1 gene fused to the chloramphenicol acetyltransferase reporter gene 10 nM TCDD significantly induced chloramphenicol acetyltransferase activity; in cells cotreated with TCDD plus E2 the induced response was not affected by the hormone. Nuclear extracts from cells treated with dimethyl sulfoxide, E2, TCDD, and TCDD plus E2 were incubated with the [32P]dioxin-responsive element and analyzed by gel electrophoretic mobility shift assays. A retarded band associated with formation of a [32P]dioxin-responsive element-AhR complex was observed in nuclear extracts from cells treated with TCDD or TCDD plus E2 (cotreated). Collectively these studies suggest that E2 does not modulate AhR-mediated CYP1A1 gene expression in MCF-7 or Hepa 1c1c7 cells.

Animals↗