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Biomedical subjects

J Wilson

Publications and source records attributed to J Wilson.

At least 145 records · Page 8Linked to original sources
PubMed2000

Weekly dosing of fluoxetine for the continuation phase of treatment of major depression: results of a placebo-controlled, randomized clinical trial.

Fluoxetine (FLX) has a unique pharmacokinetic profile. Its major metabolite, norfluoxetine (NFLX), possesses FLX's antidepressant efficacy and a half-life of 7 to 15 days, suggesting the possibility of nonstandard dosing strategies. This study examined the tolerability of a weekly dose and its equivalence to daily dosing of FLX for the continuation phase of treatment for major depressive disorder (MDD). One hundred fourteen subjects initially received open-label treatment with 20 mg of FLX daily for 7 weeks. Subsequently, 70 subjects with a score on the Hamilton Rating Scale for Depression (HAM-D) of 12 or less were randomly assigned in a double-blind design to one of three treatment groups: 20 mg FLX daily (N = 21), 60 mg FLX weekly (N = 28), or placebo (N = 21) and were followed for 7 weeks. HAM-D scores and blood levels of FLX and NFLX were analyzed using a repeated-measures analysis of variance. During the double-blind phase, blood levels for both FLX and NFLX differed across the treatment groups, yet no statistically significant difference in HAM-D scores was observed. There was no difference in the dropout rate across the groups. Subjects could not correctly identify the treatment group into which they were assigned. Weekly dosing of FLX seems to be well tolerated and possibly as effective as daily dosing in maintaining the therapeutic response in subjects with MDD.

Adult↗
PubMed2000

The use of wavelet transforms in low-resolution phase extension.

A method to extend low-resolution phases has been developed using histogram matching not only of the electron density itself but also of histograms obtained from the different levels of detail provided by the wavelet transform of the electron density. It is shown that the method can extend phases from 10 A to around 6-7 A on a wide range of trial structures differing in size, space group and solvent content. This level of phase extension can improve the electron-density map from little more than a molecular envelope to one in which secondary structure can often be identified.

Bacterial Proteins↗
PubMed2000

Wavelet analysis of electron-density maps.

The wavelet transform is a powerful technique in signal processing and image analysis and it is shown here that wavelet analysis of low-resolution electron-density maps has the potential to increase their resolution. Like Fourier analysis, wavelet analysis expresses the image (electron density) in terms of a set of orthogonal functions. In the case of the Fourier transform, these functions are sines and cosines and each one contributes to the whole of the image. In contrast, the wavelet functions (simply called wavelets) can be quite localized and may only contribute to a small part of the image. This gives control over the amount of detail added to the map as the resolution increases. The mathematical details are outlined and an algorithm which achieves a resolution increase from 10 to 7 A using a knowledge of the wavelet-coefficient histograms, electron-density histogram and the observed structure amplitudes is described. These histograms are calculated from the electron density of known structures, but it seems likely that the histograms can be predicted, just as electron-density histograms are at high resolution. The results show that the wavelet coefficients contain the information necessary to increase the resolution of electron-density maps.

Algorithms↗
PubMed2000

Low-resolution phase extension using wavelet analysis.

A method to extend low-resolution phases is presented which uses histogram matching not only of the electron density, but also of histograms obtained from the different levels of detail provided by the wavelet transform of the electron density. Statistical values for the wavelet coefficients can be predicted and depend only on the resolution and solvent content. Therefore, new details can be added to an electron-density map by matching the values of the wavelet coefficients to those predicted for an increased resolution. The positions of the new details are also guided by the diffraction pattern. In this way, the resolution can be increased gradually; on a number of trial structures of different size, solvent percentage and space group, it has been possible to extend the phasing from 10 A to around 6-7 A.

Electrons↗
PubMed2000

Dominant nonresponsiveness to Helicobacter pylori infection is associated with production of interleukin 10 but not gamma interferon.

Helicobacter pylori-induced gastritis is an essential precursor lesion for the development of peptic ulcers or gastric adenocarcinoma. We demonstrate that nonresponsiveness to H. pylori SS1 infection is dominantly inherited in mice. F(1) hybrid crosses between a nonresponder mouse and three responder strains all possessed the nonresponder phenotype. Secretion of interleukin-10 but not gamma interferon was associated with nonresponsiveness to infection.

Adenocarcinoma↗
PubMed2000

CD40 ligand-dependent activation of cytotoxic T lymphocytes by adeno-associated virus vectors in vivo: role of immature dendritic cells.

Recombinant adeno-associated virus type 2 (rAAV) is being explored as a vector for gene therapy because of its broad host range, good safety profile, and persistent transgene expression in vivo. However, accumulating evidence indicates that administration of AAV vector may initiate a detectable cellular and humoral immune response to its transduced neo-antigen in vivo. To elucidate the cellular basis of the AAV-mediated immune response, C57BL/6 mouse bone marrow-derived immature and mature dendritic cells (DCs) were infected with AAV encoding beta-galactosidase (AAV-lacZ) and adoptively transferred into mice that had received an intramuscular injection of AAV-lacZ 10 days earlier. Unexpectedly, C57BL/6 mice but not CD40 ligand-deficient (CD40L(-/-)) mice adoptively transferred with AAV-lacZ-infected immature DCs developed a beta-galactosidase-specific cytotoxic T-lymphocyte (CTL) response that markedly diminished AAV-lacZ-transduced gene expression in muscle fibers. In contrast, adoptive transfer of AAV-lacZ-infected mature DCs failed to elicit a similar CTL response in vivo. Our findings indicate, for the first time, that immature DCs may be able to elicit a CD40L-dependent T-cell immunity to markedly diminish AAV-lacZ transduced gene expression in vivo when a sufficient number of DCs capturing rAAV vector and/or its transduced gene products is recruited.

Adoptive Transfer↗
PubMed2000

Airway distensibility in healthy and asthmatic subjects: effect of lung volume history.

Anatomic dead space (VD) is known to increase with end-inspiratory lung volume (EILV), and the gradient of the relationship has been proposed as an index of airway distensibility (DeltaVD). The aims of this study were to apply a rapid method for measuring DeltaVD and to determine whether it was affected by lung volume history. VD of 16 healthy and 16 mildly asthmatic subjects was measured at a number of known EILVs by using a tidal breathing, CO(2)-washout method. The effect of lung volume history was assessed by using three tidal breathing regimens: 1) three discrete EILVs (low/medium/high; LMH); 2) progressively decreasing EILVs from total lung capacity (TLC; TLC-RV); and 3) progressively increasing EILVs from residual volume (RV; RV-TLC). DeltaVD was lower in the asthmatic group for the LMH (25.3 +/- 2.24 vs. 21.2 +/- 1.66 ml/l, means +/- SE) and TLC-RV (24. 3 +/- 1.69 vs. 18.7 +/- 1.16 ml/l) regimens. There was a trend for a lower DeltaVD in the asthmatic group for the RV-TLC regimen (23.3 +/- 2.19 vs. 18.8 +/- 1.68 ml/l). There was no difference in DeltaVD between groups. In conclusion, mild asthmatic subjects have stiffer airways than normal subjects, and this is not obviously affected by lung volume history.

Adult↗
PubMed2000

Hyperbaric oxygen reduces the progression and accelerates the regression of atherosclerosis in rabbits.

We studied the effect of hyperbaric oxygen (HBO) treatment on the extent of diet-induced accumulation of lipid oxidation products in rabbit plasma and tissues, on plasma paraoxonase activity, and on the extent of progression and regression of atherosclerotic lesions in the rabbit aorta. HBO treatment of cholesterol-fed rabbits dramatically reduces the development of arterial lesions despite having little or no effect on plasma or individual lipoprotein cholesterol concentrations. Compared with no treatment in cholesterol-fed animals, HBO treatment also substantially reduces the accumulation of lipid oxidation products (conjugated dienes, trienes, and thiobarbituric acid-reactive substances) in plasma, in the low density lipoprotein and high density lipoprotein fractions of plasma, in the liver, and in the aortic tissues. In addition, HBO treatment prevents the decrease in plasma paraoxonase activity observed in rabbits fed cholesterol-rich diets. Similarly, in regression studies, HBO treatment has no effect on the rate of plasma (or lipoprotein) cholesterol decline but significantly accelerates aortic lesion regression compared with no treatment. Direct measures of aortic cholesterol content support these morphological observations. On the basis of these results, we conclude that repeated, but relatively short, exposure to HBO induces an antioxidant defense mechanism(s) that is responsible for retarding the development or accelerating the regression of atherosclerotic lesions.

Animals↗
PubMed2000

Respiratory viral infections in adults with and without chronic obstructive pulmonary disease.

A longitudinal cohort study of older adults with chronic obstructive pulmonary disease (COPD) who were stratified by FEV(1) at enrollment was done to define the etiology, frequency, severity, and medical-care impact of respiratory tract viral infections (RTVIs). Controls consisted of a group of subjects of comparable age with the patients. RTVIs were documented in 44% of observed acute respiratory illnesses in control subjects and in 27% of COPD subjects, who were followed for mean periods of 35 and 26 mo, respectively. In this heavily influenza-vaccinated cohort ( approximately 90% vaccinated each year), picornaviruses, parainfluenza viruses, and coronaviruses were most commonly identified. Mean time to return to clinical baseline was approximately 2 wk in each group. Control and COPD subjects with mild airways obstruction (baseline FEV(1) >/= 50% predicted) had few emergency-center visits or hospitalizations. Approximately half of COPD subjects with moderate/severe COPD (baseline FEV(1) < 50% predicted) had at least one emergency-center visit and/or hospitalization for acute respiratory illness. RTVIs were documented in 23% of hospitalizations and in 45% of patients admitted between December and March. RTVIs have a major impact on utilization of health care resources for COPD patients with moderate/severe airways obstruction.

Aged↗
PubMed2000

An economic evaluation comparing two schedules of antenatal visits.

OBJECTIVES: To conduct an economic evaluation comparing a traditional antenatal visiting schedule (traditional care) with a reduced schedule of visits (new style care) for women at low risk of complications. METHODS: Economic evaluation using the results of a randomised controlled trial, the Antenatal Care Project. This took place between 1993 and 1994 in antenatal clinics in South East London and involved 2794 women at low risk of complications. RESULTS: The estimated baseline costs to the UK National Health Service (NHS) for the traditional schedule were 544 Pounds per woman, of which 251 Pounds occurred antenatally, with a range of 327-1203 Pounds per woman. The estimated baseline costs to the NHS for the reduced visit schedule was 563 Pounds per woman, of which 225 Pounds occurred antenatally, with a range of 274-1741 Pounds per woman. Savings from new style care that arose antenatally were offset by the greater numbers of babies in this group who required special or intensive care. Sensitivity analyses based on possible variations in unit costs and resource use and modelled postnatal stay showed considerable variation and substantial overlap in costs. CONCLUSIONS: Patterns of antenatal care involving fewer routine visits for women at low risk of complications are unlikely to result in savings to the Health Service. In addition, women who had the reduced schedule of care reported greater dissatisfaction with their care and poorer psychosocial outcomes which argues against reducing numbers of antenatal visits.

Cost-Benefit Analysis↗
PubMed2000

Can traumacel be used in the treatment of chronic wounds?

Traumacel (calcium salt of oxidised cellulose) has previously only been used in the treatment of acute wounds. To assess its safety and effectiveness in the management of chronic wounds a 12-week pilot study was undertaken which involved 11 patients with 15 non-healing leg ulcers and assessed ulcer size, ulcer pain and degree of exudate. Five ulcers healed within the study period. Significant pain relief was experienced by three patients. Use of the dressing did not appear to be related to a reduction in exudate. No patients experienced sensitisation to the product or had to be withdrawn because of adverse effects. Traumacel was found to be safe in the management of chronic ulceration, and appeared to promote healing in some recalcitrant ulcers.

Aged↗
PubMed2000

Studies of HLA-DR and DQ alleles in systemic sclerosis patients with autoantibodies to RNA polymerases and U3-RNP (fibrillarin).

OBJECTIVE: To determine the clinical and immunogenetic features of systemic sclerosis (SSc) patients with anti-RNA polymerase (RNAP) or anti-fibrillarin antibodies. METHODS: DNA typing for HLA-DR and DQ alleles was performed in 292 patients with SSc, including 81 with anti-RNAP and 24 with anti-fibrillarin antibodies. The remaining patients had anti-topoisomerase I (anti-topo I; 71), anti-centromere (ACA; 56), anti-Th/To (28), or other antinuclear (32) antibodies. RESULTS: Significant associations were observed in the patients with anti-topo I, ACA, and anti-Th/To antibodies, similar to those previously reported. No significant HLA associations were detected in the 81 patients with anti-RNAP. although weak associations were noted when this group was subdivided on the basis of immunofluorescence staining pattern; i.e., HLA-DR4 was increased in patients with strong nucleolar staining and HLA-DR3 was more frequent in patients with nucleoplasm staining only. No HLA-DR or DQ associations were observed in 24 patients with anti-fibrillarin antibodies. CONCLUSION: The identification of HLA associations in SSc patients with anti-RNAP antibodies may only be possible when the individual antibody specificities recognized by these sera are identified. It may then be possible to classify these patients into distinct clinical and immunogenetic subgroups.

Alleles↗
PubMed2000

Changes in egg composition of American kestrels exposed to dietary polychlorinated biphenyls.

Changes in the quality of eggs of birds exposed to polychlorinated biphenyls (PCBs) have been described, but have never been directly attributed to PCBs. Polychlorinated biphenyl residues in eggs have been associated with reduced reproductive success and embryonic deformities in wild birds. Egg size and composition, specifically the amount of albumen, yolk, and water in an egg, also influence the growth and viability of embryos and hatchlings, and consequently the reproductive success of birds. To deter mine whether PCB exposure of adult birds affected the size and composition of their eggs, 25 pairs of captive American kestrels (Falco sparverius) were fed a mixture of PCB-spiked (1248:1254:1260) food to give an approximate exposure of 7 mg/kg body weight/d, beginning 1 mo prior to pairing, and continuing throughout the courtship, egg-laying, and incubation periods. This dietary level in the adult female kestrels resulted in mean total PCB residues in the eggs of 34.1 microg/g wet weight (geometric mean), which is environmentally relevant. PCB residues in eggs increased with the time of female exposure to the contaminated diet and laying date. Variation in egg size within PCB clutches was significantly greater than within control clutches, although absolute egg mass and volume did not differ markedly by treatment. Only infertile eggs and only one egg per clutch were used for egg composition analysis. Yolks in the PCB-contaminated eggs were heavier, with less wet and dry albumen relative to control eggs. Water content and eggshell thickness were not significantly affected by PCB exposure. These results suggest that eggs from the PCB treatment have relatively more lipid and less protein available for embryonic development. Changes in egg composition were not associated with egg size, lay date, ambient temperature, humidity, or precipitation, which are factors known to affect these variables in bird eggs. The PCB-induced changes in egg composition described here provide insight into possible mechanisms contributing to reduced reproductive performance in wild birds exposed to PCBs.

Administration, Oral↗
PubMed2000

Antenatal visits.

Explore the source record for details and available documents.

Appointments and Schedules↗
PubMed1999

CD40 cross-linking enhances the immunogenicity of Burkitt's-lymphoma cell lines.

Epstein-Barr-virus (EBV)-positive Burkitt's-lymphoma (BL) cell lines are not recognized by EBV-specific T cells, due to their non-immunogenic phenotype and restricted expression of latent EBV genes. We tested whether triggering of CD40 can alter the phenotype of the tumor cells with regard to: (i) expression of surface markers, (ii) expression of viral antigens, (iii) presentation of endogenous antigens to MHC-class-1 restricted cytotoxic T lymphocytes (CTLs), (iv) stimulatory capacity in allogeneic mixed-lymphocyte cultures (MLCs), (v) sensitivity to natural-killer (NK)-cell-mediated lysis. Co-culture of EBV-positive BL cells with CD40-ligand-transfected L cells induced up-regulation of CD54 and CD80 but did not affect the expression of viral genes. In spite of significant up-regulation of TAP1 and TAP2, and increased expression of MHC class 1, the BL cells remained unable to present endogenously expressed viral antigens to EBV-specific CTL. However, the up-regulation of adhesion and co-stimulatory molecules was associated with increased stimulatory capacity in MLC and enhanced sensitivity to NK cells. These findings indicate that, while inducing only a modest phenotype shift, cross-linking of CD40 under physiologic conditions may selectively enhance the sensitivity of BL cells to anti-tumor immune responses.

ATP Binding Cassette Transporter, Subfamily B, Mem↗