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Biomedical subjects

E Wheeler

Publications and source records attributed to E Wheeler.

At least 19 recordsLinked to original sources
PubMed2006

Genome-wide scan for loci influencing quantitative immune response traits in the Belém family study: comparison of methods and summary of results.

Here we report the results from a genome-wide linkage scan to identify genes and chromosomal regions that influence quantitative immune response traits, using multi-case leprosy and tuberculosis families from north-eastern Brazil. Total plasma IgE, antigen-specific IgG to Mycobacterium leprae soluble antigen (MLSA), M. tuberculosis soluble antigen (MTSA) and M. tuberculosis purified protein derivative (PPD), and antigen-specific lymphocyte proliferation (stimulation index or SI) and interferon-gamma (IFN-gamma) release to MLSA and PPD, were measured in 16 tuberculosis (184 individuals) and 21 leprosy (177 individuals) families. The individuals were genotyped at 382 autosomal microsatellite markers across the genome. The adjusted immune-response phenotypes were analysed using a variety of variance components and regression-based methods. These analyses highlighted a number of practical issues and problems with regard to implementation of the methods and, interestingly, differences were observed between several standard statistical and genetic analysis packages used. From this we determined that, for this set of traits in these pedigrees, significant p values for linkage using variance components analysis, supported by significance using the Visscher-Hopper modification of the Haseman-Elston method, provided the most compelling evidence for linkage. Using these criteria, linkage (5.8 x 10(-5) < p < 0.008) was seen for: total plasma IgE on chromosome 2; IgG to MLSA on chromosomes 8, 17 and 21; IgG to PPD on chromosome 12; SI to PPD on chromosome 1; IFN-gamma to MLSA on chromosomes 6, 7, 10, 12 and 14; and IFN-gamma to PPD on chromosomes 1, 16 and 19.

Analysis of Variance↗
PubMed2004

Brain-derived neurotrophic factor is expressed in a gradient in the superior colliculus during development of the retinocollicular projection.

Abstract Theoretical models of topographic map formation have postulated a gradient of attractant in addition to a gradient of repulsion in the target. In species where many axons grow past their correct positions initially, it has also been argued that a parallel gradient of attractant or branching signal is required to ensure collateral formation at the correct position (O'Leary et al., 1999). Brain-derived neurotrophic factor (BDNF) is a known attractant and promotes branching of retinal axons. We have examined its distribution in the superior colliculus and that of its receptor, trkB, in the retina, using immunohistochemistry and in situ hybridization, respectively, during the development of the topographic retinocollicular projection in the wallaby, a marsupial mammal. The number of glial endfeet expressing BDNF at the surface of the colliculus was found to be in a high caudal-to-low rostral gradient during the time when the retinocollicular projection was developing. When the projection was mature the rostrocaudal gradient had disappeared and the number of detectable endfeet expressing BDNF was very low. Messenger RNA for TrkB was expressed in the retinal ganglion cell layer throughout the time when the retinocollicular projection was developing, with no difference in expression across the nasotemporal axis of the retina. The low rostral to high caudal distribution of BDNF in glial endfeet supports the idea that it is providing a parallel gradient of attractant or branching signal in the colliculus.

Aging↗
PubMed2003

The National Health Service Breast Screening Programme and British Association of Surgical Oncology audit of quality assurance in breast screening 1996-2001.

BACKGROUND: The National Health Service Breast Screening Programme (NHSBSP) is an example of a nationally coordinated quality assurance programme in which all the professional groups involved participate. METHODS: Surgeons, radiologists and pathologists defined the clinical outcome measures against which they would subsequently be audited. The NHSBSP and the Association of Breast Surgery at BASO are jointly responsible for coordinating an annual audit of all surgical activities undertaken within the NHSBSP. RESULTS: The trends for key outcome measures between 1996 and 2001 are provided. The preoperative diagnosis rate (minimum standard 70 per cent or more) improved from 63 to 87 per cent. This rise was mirrored by an increase in the use of core biopsy in preference to fine-needle cytology. The proportion of patients in whom lymph node status was recorded improved from 81 to 93 per cent. There was no significant change in the number of women treated by low case-load surgeons and waiting times for surgery increased through the study interval. CONCLUSION: The BASO-NHSBSP Breast Audit has recorded major changes in clinical practice over 5 years. A key feature has been the dissemination of good practice through feedback of the results at local and national level.

Biopsy, Needle↗
PubMed1999

An HIM survival kit for the year 2000.

Is your organization ready for the Year 2000? The "millennium bug" offers some useful lessons in risk assessment. Here's how to build a contingency plan to ensure business continuity on January 1, 2000.

Chronology as Topic↗
PubMed1996

Bovine oocyte plasma membrane binding sites for sperm plasma membrane during in vitro oocyte maturation and fertilisation.

The experimental objective was to determine whether the capability of bovine oocyte plasma membrane to bind sperm changes during in vitro oocyte maturation and fertilisation. Binding was quantified by the intensity of tetramethylrhodamine isothiocyanate (TRITC) fluorescence at the periphery of oocytes following incubation with biotinylated sperm plasma membrane proteins and subsequent incubation with TRITC-avidin. Bovine oocytes were matured in vitro. Sample groups were removed after 0,6 and 22 h, or inseminated and further cultured for 24 or 48 h. Oocytes were denuded of cumulus cells and zona pellucida and co-incubated with 56 micrograms biotinylated bovine sperm plasma membrane protein for 45 min in 150 microliters drops of saline-BSA. Controls were incubated for the same time period in the absence of sperm plasma membrane proteins. All oocytes were rinsed, incubated with TRITC-avidin and subsequently fixed and transferred to mounting medium. Oocytes were scanned with a confocal microscope and analysed using ImageQuant software. The binding of sperm plasma membrane was quantified by integrated fluorescent intensity in standardised ellipses spaced around the plasma membrane of the oocyte. Values are expressed as mean intensity units per 320 pixel ellipse. Binding of sperm plasma membrane continued to increase throughout in vitro oocyte maturation and fertilisation (9051, 24318 and 49953 for 0 and 22 h in vitro matured oocytes and fertilised oocytes, respectively; p = 0.0001). A dramatic decrease in sperm plasma membrane binding to the oocyte plasma membrane was observed in 2-cell embryos (mean intensity = 24477, p = 0.0001). The observed binding was primarily due to the binding of sperm plasma membrane proteins, as control oocytes incubated with TRITC-avidin only were barely visible (integrated fluorescence intensity values ranged from 8 to 3757.

Animals↗
PubMed1993

The energy and nutrient intakes of different types of vegetarian: a case for supplements?

Vegetarians of three types were studied in Greater London: thirty-four meat-avoiders, fifty-two lacto-ovo-vegetarians, and thirty-eight vegans. Weighed dietary intake measures were made over 3 d. Cereals were the mainstay of the diet, supplemented by dairy products (demi-vegetarians and lacto-ovo-vegetarians), vegetables and fruit, and soya-bean products (vegans). Many vegans progressed by stages to complete avoidance of animal foods; some had retreated, but most were highly committed. Demi-vegetarians were the least involved in a 'vegetarian lifestyle'. All groups had mean energy intakes close to the current dietary reference values (DRV), with adequate protein intakes. Only vegans had fat intakes close to current recommendations; all groups had high dietary polyunsaturated:saturated fatty acid ratios. Mean intakes of all micronutrients studied for demi- and lacto-ovo-vegetarians met the UK DRV. Intakes of iodine, riboflavin, and vitamin B12 for vegans were below DRV; more than half considered their diets supplied all necessary vitamins. About 25% took some type of dietary supplement during the survey. The impact of low I intakes should be further studied, and it is recommended that 'new' vegetarians and vegans should use appropriate dietary supplements.

Adult↗
PubMed1989

Phosphorylation of cytoskeleton-associated proteins, pp58 and pp60, in tumouricidal murine peritoneal macrophages.

Two highly phosphorylated vimentin-like proteins, pp58 and pp60, are expressed in macrophages activated in vivo to tumouricidal activity. Resident and elicited, non-tumouricidal peritoneal macrophages displayed low and intermediate levels of phosphorylated pp58 and pp60, respectively. C3H/HeN macrophages became tumouricidal after incubation with 0.1 micrograms/mL A23187 plus 10 nmol/L 12-phorbol 13-myristate acetate (PMA), or 0.1 micrograms/mL A23187 plus 100 ng/mL lipopolysaccharide (LPS), and displayed increased phosphorylation of pp58 and pp60. LPS non-responder C3H/HeJ macrophages were not tumouricidal nor did they show increased phosphorylation of pp58 and pp60 after incubation with LPS plus A23187 in vitro. C3H/HeJ macrophages, however, did become tumouricidal and expressed increased phosphorylation of pp58 and pp60 after incubation with A23187 and PMA. Addition of PGE2 (10(-8) mol/L), resulted in down-regulation of macrophage tumouricidal activity and decreased pp58 and pp60 phosphorylation, which was reversed by addition of indomethacin (10(-6) mol/L) to cultures with PGE2. Phosphorylation increased within 5 min after adding activating stimuli while incorporation of [35S]-methionine into a 58 kD protein did not occur until 6 h later. No 60 kD protein synthesis was detected during the first 8 h after adding activating stimuli, indicating that previously synthesized proteins were phosphorylated during macrophage activation. These results signify a physiological role for the phosphorylation of cytoskeleton-associated pp58 and pp60 during macrophage activation to tumour cytotoxicity.

Animals↗
PubMed1989

The diets of pregnant and post-pregnant women in different social groups in London and Edinburgh: calcium, iron, retinol, ascorbic acid and folic acid.

Dietary records were obtained twice in pregnancy and once post-partum, from 265 women in all social classes in London and Edinburgh. Some Edinburgh women, and lactating women, showed the higher levels of calcium intake. For iron, retinol, ascorbic acid and folic acid, there was a consistent and significant regional and social class gradient in intakes. This favoured English women in 'non-manual' social groups, leaving the Scottish 'manual' class, after pregnancy, with the lowest intakes. Mean intakes of Ca and Fe were consistently below the current UK recommended daily amount (RDA). Intakes of retinol were all above it, and ascorbic acid intakes ranged above and below the RDA.

Ascorbic Acid↗
PubMed1988

Characterization of two highly phosphorylated cytoskeleton-associated proteins, pp58 and pp60, in tumoricidal murine peritoneal macrophages and their comparison with vimentin.

Two TX-insoluble cytoskeleton-associated proteins, pp58 and pp60, become highly phosphorylated in tumoricidal murine peritoneal macrophages. Results suggest that pp58 (pI 5.00) is phosphovimentin because it is highly insoluble in TX, shares the same mol. wt as vimentin, has a more acidic isoelectric point than vimentin, is phosphorylated primarily at serine, and generates the same V-8 protease peptide map as vimentin. pp60 generates at slightly different peptide map than pp58 and has a slightly less acidic isoelectric point (pI 5.02) than pp58 (pI 5.00), but is similar to pp58 by being highly insoluble in TX and being phosphorylated primarily at serine residues. Pulse-chase experiments demonstrate that pp58 is not a precursor to or breakdown product of pp60, or vice versa because they show similar rates of [32P]-phosphate incorporation and turnover.

Animals↗
PubMed1987

The diets of pregnant and post-pregnant women in different social groups in London and Edinburgh: energy, protein, fat and fibre.

1. Dietary records were obtained twice in pregnancy and once post-partum from 265 women from all social classes in London and Edinburgh. 2. The London women always had higher mean energy, protein, fat and fibre intakes. Significant between-region differences emerged. 3. Some between-social classes differences occurred, but were not consistently significant. 4. All mean energy and fibre intakes were lower, and protein and fat intakes were higher, than current recommendations. 5. Of lactating women 15% claimed to be dieting. 6. The percentage dietary energy derived from fat varied from 36 (in a dieting group) to 42.

Adolescent↗
PubMed1986

Macrophage-mediated suppression of natural killer cell activity in mice bearing Lewis lung carcinoma.

The natural killer (NK) cell cytotoxic capacity of C57BL/6 mice with implantation of Lewis lung carcinoma (LLC) was quantitated during tumor growth. The NK activity became suppressed at 1 week of tumor growth and remained suppressed. The mechanisms for the suppression during the first 3 weeks of tumor growth included secretion of prostaglandin E2 (PGE2) by both the LLC tumor and host macrophages. With tumor growth, plasma PGE2 concentrations progressively increased. Oral administration of indomethacin to tumor-bearing mice prevented the rise in serum PGE2 concentrations and the suppression of NK activity. Cultured LLC cells and splenic macrophages isolated from mice during the first 3 weeks of tumor growth secreted increased amounts of PGE2. Macrophages from tumor-bearer spleen cells were shown to suppress NK activity. Depletion of these macrophages restored the NK activity, and addition of these macrophages to normal spleen cells resulted in an indomethacin-sensitive suppression of the NK response. The mechanisms of suppression in mice bearing large tumors were different than those observed with smaller tumors. With a large tumor burden, the plasma PGE2 concentrations declined. Indomethacin treatment did not prevent the suppression of NK activity, and depletion of splenic macrophages did not restore NK cytotoxicity.

Animals↗
PubMed1977

Selective mobilization of specifically cytotoxic T-lymphocytes at sites of inflammation in relation to BCG-induced resistance to implants of syngeneic sarcoma in mice.

The heightened and long-persisting resistance of BCG--immunized C57BL/6 mice (10-week-old males and females) to challenge with syngeneic sarcoma cells was largely restricted to the site of inoculation of the BCG. The specific cytotoxicity of peritoneal T-cells and the total number of T-cells that could be recovered from the peritoneal cavity were more than ten times greater in mice that had received BCG ip 2-4 weeks prior to inoculation of tumor than in non-BCG-treated mice. The specific T-cell-mediated cytotoxic potential of the peritoneal exudate of mice immunized with tumor was therefore at least 100 times greater in mice that had received BCG ip. This effect was detectable by 3 days after inoculation of BCG and reached a maximum 2-4 weeks later. The protection against tumor offered by pretreatment with BCG could be explained by the selective recruitment of committed T-lymphocytes to sites of chronic inflammation. The induction of nonspecifically cytotoxic macrophages and systemic changes such as generalized stimulation of the reticuloendothelial system were not contributing factors.

Animals↗
PubMed1976

Marital therapy in groups. A comparative evaluation of behavioral and interactional formats.

A comparative evaluation was conducted in a community mental health center between two types of brief, marital therapy in groups. The experimental group of four couples was exposed to behavioral methods based on social learning principles. The primary interventions were (1) training the spouses in discriminating and monitoring the occurrence of pleasing events and behaviors; (2) behavioral rehearsal of communication skills using prompting, modelling, feedback, and "homework" assignments; and (3) contingency contracting. The comparison group of five couples was led in an interactional format with the leaders encouraging ventilation of feelings, problem-solving through discussion, and mutual support and feedback. Both groups were led by the same three clinicians. Outcome was measured on multiple levels before, during and immediately after treatment. Follow-up assessments were conducted at one, two, and six months after treatment. Response measures included the self report by clients on marital satisfaction; on consumer satisfaction with the treatment experience; on their observations of pleasing behaviors given and received as recorded on wrist counters; and direct observation of client via "live" time-sampling and coding of videotapes of problem-solving discussions before and after treatment. Results showed few differences between groups on the self-report measures; however, there were significant improvements by both groups on these measures after treatment which were maintained into the follow-up evaluation. The direct observational data indicated that the members in the behavioral group displayed significantly more positive and mutually supportive verbal and nonverbal behaviors in their interaction as a result of treatment.

Behavior Therapy↗
PubMed1973

Similarities of the anti-tumour actions of endotoxin, lipid A and double-stranded RNA.

Double stranded RNA (dsRNA) whether isolated from a fungal virus or prepared synthetically (i.e., Poly I Poly C) and endotoxin were found to exert very similar effects on syngeneic murine lymphomata and fibrosarcomata. They cause complete regressions of some established subcutaneous (s.c.) or intradermal (i.d.) tumours but not of intraperitoneal (i.p.) tumours when administered either systemically or directly into the tumour. To achieve this effect the tumours must be fully established and the best results were obtained when treatment was started 7 days after transplant. If treatment is started within the first 3 days following the transplantation of the tumour then only a slight inhibition of growth rate was observed. These agents can also act prophylactically and protect mice against a subsequent challenge but only if this is given i.p. and not if given s.c. or i.d. The prophylactic action is explained by the action of dsRNA and endotoxin on peritoneal macrophages which cause them to become cytotoxic to tumour cells (i.e., to become activated).The therapeutic effect of systemically administered endotoxin and dsRNA on established tumours is not the result of a direct action on the tumour cells themselves but is a complex process requiring the co-operation of several host factors. Haemorrhagic necrosis involving coagulation is essential (i.e., heparinization reduces the regression of tumours) but is not itself sufficient. Immunosuppression by whole body irradiation or by antilymphocyte serum also interferes with the antitumour action of dsRNA and endotoxin in spite of the fact that haemorrhagic necrosis still occurs. Also, the magnitude of the antitumour action correlated in a series of different tumours with their antigenicity. The observed tumour regressions are probably brought about by (1) vascular damage in the tumour which permits immune defence mechanisms of the host to gain access to the tumour and (2) activation of macrophages present within the tumour. The relative contribution of these two mechanisms may depend on the nature of the tumour and the route of administration of the active agents.Dibenyline, which protects against the lethal action of endotoxin by preventing the action of the catecholamines on the α-adrenergic receptors, makes it possible to increase the effectiveness of endotoxin in tumours by allowing a large dose to be given. Lipid A, a derivative of endotoxin which does not contain polysaccharide, has similar antitumour action to dsRNA and endotoxin. Some common features of the chemical structure of lipid A and dsRNA are discussed.

Animals↗