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Biomedical subjects

J D Wilson

Publications and source records attributed to J D Wilson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Prospects for research for disorders of the endocrine system.

Endocrine disorders, primarily diseases of the thyroid, parathyroids, pituitary, gonad, and adrenal glands, constitute a major health problem in all societies. As a result of improved insight into the diagnosis, pathophysiology, and molecular bases, it is now possible to diagnose the disorders earlier in their development, and the treatment of the deficiency states for most hormones is successful. Furthermore, with recognition that many of these disorders are either the consequence of single-gene mutations or have a major genetic component, it is now possible to diagnose affected fetuses and family members at risk. Therapies for the syndromes of hormone overproduction are less successful and frequently result in destruction of the endocrine organ involved, and the treatment of hormone resistance states is similarly unsatisfactory. These disorders are candidates for the development of superagonists/antagonists and gene therapies.

Animals↗
PubMed2001

Androgens, androgen receptors, and male gender role behavior.

Studies of genetic males with single gene mutations that impair testosterone formation or action and consequently prevent development of the normal male phenotype provide unique insight into the control of gender role behavior. 46,XY individuals with either of two autosomal recessive mutations [17 beta-hydroxysteroid dehydrogenase 3 (17 beta-HSD3) deficiency or steroid 5 alpha-reductase 2 (5 alpha-R2) deficiency] have a female phenotype at birth and are raised as females but frequently change gender role behavior to male after the expected time of puberty. In contrast, genetic males with mutations that impair profoundly the function of the androgen receptor are also raised as females and have consistent female behavior as adults. Furthermore, the rare men with mutations that impair estrogen synthesis or the estrogen receptor have male gender role behavior. These findings indicate that androgens are important determinants of gender role behavior (and probably of gender identity) and that this action is mediated by the androgen receptor and not the result of conversion of androgen to estrogen. The fact that all genetic males with 17 beta-HSD3 or 5 alpha-R2 deficiency do not change gender role behavior indicates that other factors are also important determinants of this process.

Androgens↗
PubMed2001

Cultural ecology of Whitethroat (Sylvia communis) habitat management by farmers: field-boundary vegetation in lowland England.

Field-boundary structure, its use by territorial Whitethroats, and its management by farmers were investigated in southern Wiltshire using a combination of fieldwork and a questionnaire survey. Whitethroats favour wide herbaceous field boundary strips and low hedges. Long-term cultural and short-term economic interests combine to influence farmers' management decisions. Only farmers with game and conservation interests claimed to adopt field-boundary management that would benefit Whitethroats, but across all farms, intended and actual herbaceous strips were too narrow, and their management too imprecise, for Whitethroats and other wildlife. Agricultural advisors and magazines were the main influences on farmers' management decisions. Improving habitat for Whitethroats could have both agronomic and wider conservation benefits, and the provision of information that accommodates farmers' cultural and economic incentives could benefit both farmers and wildlife.

Agriculture↗
PubMed2001

Cultural ecology of Whitethroat (Sylvia communis) habitat management by farmers: winter in farmland trees and shrubs in Senegambia.

The presence of Whitethroats and their potential invertebrate prey in farmland trees and shrubs was investigated. The management of this vegetation by farmers, and their motivation for that management, was explored using participatory techniques. Whitethroats were associated with Guiera senegalensis, the shrub species which supports most caterpillars and spiders. Farmers reported declines in trees and shrubs since the 1950s, loss of fallow areas, declines in soil fertility and crop yields, and increases in the use of fire for clearing fields. Trees are valued by people for their cultural and medicinal uses and some species used by Whitethroats and other birds have potential for restoring soil fertility, although this was not recognised by farmers. More sustainable use of savanna farmland could have both agronomic and wider conservation benefits, and the provision of information that accommodates farmers' cultural and economic incentives could benefit both farmers and wildlife.

Animals↗
PubMed2001

Bielschowsky bodies (Lafora bodies of Bielschowsky type): report of a case associated with Rosenthal fibers in the brain stem.

Bielschowsky bodies are an uncommon type of polyglucosan body. Similar to Lafora bodies, they are characteristically identified within neuronal perikarya and neurites. However, they lack the diffuse distribution of Lafora bodies, and instead are typically restricted to the external pallidum, often in association with status marmoratus or atrophy of the putamen. Fewer numbers of Bielschowsky bodies have also been identified in other areas such as the substantia nigra, putamen and inner globus pallidus. We report an additional case with Bielschowsky bodies in an 18-year old female with cerebral palsy. This case demonstrated multifocal Bielschowsky bodies and abundant Rosenthal fibers in the midbrain and pons. To our knowledge the association of Bielschowsky bodies with this peculiar distribution of Rosenthal fibers has not previously been reported.

Adolescent↗
PubMed2001

Microsatellite variation in the yellowhammer Emberiza citrinella: population structure of a declining farmland bird.

In recent years, there has been much concern in the UK about population declines of widespread species in agricultural habitats. Conservation-orientated research on declining birds has focused on vital rates of survival and productivity. However, the environmental factors which may influence movements between populations of widespread species is poorly understood. Population genetic structure is an indirect description of dispersal between groups of individuals. To attempt to develop an understanding of genetic structuring in a widespread, but declining, farmland bird, we therefore investigated the yellowhammer, Emberiza citrinella, population in England and Wales using microsatellite data. Our first aim was to investigate whether there was genetic substructuring in the population. A second aim was to investigate if there was a relationship between genetic distances and various environmental variables. Finally, we analysed the microsatellite data for evidence of loss of genetic variation due to population decline. Our data showed a slight but significant structure within the yellowhammer population. This therefore cannot be considered a panmictic population. Our example from South Cumbria implies that high-altitude barriers may have a slight influence on population structure. However, on the whole, genetic distances between sample sites were not significantly correlated with geographical distances, degrees of population connectivity, high altitudes, or differences in precipitation between sites. Finally, we detected departures from mutation-drift equilibrium (excess heterozygosity), which is indicative of a loss of genetic variation through recent decline.

Alleles↗
PubMed2001

The role of 5alpha-reduction in steroid hormone physiology.

A role for 5alpha-reduction in androgen physiology was first established with the recognition that dihydrotestosterone, the 5alpha-reduced metabolite of testosterone, is formed in many androgen target tissues, binds to the androgen receptor with greater affinity than testosterone, and plays an essential role in virilization of the urogenital sinus and urogenital tubercle during male development. Two 5alpha-reductases perform this reaction, and both isoenzymes utilize NADPH as cofactor and have broad specificity for steroids containing a delta4,3-keto configuration. 5alpha-Reduction, which is essentially irreversible, flattens the steroid molecule because of altered relation of the A and B rings, and stabilizes the hormone-receptor complex. Studies involving in vitro reporter gene assays and intact mice in which both isoenzymes are disrupted, indicate that the fundamental effect of dihydrotestosterone formation is to amplify hormonal signals that can be mediated by testosterone at higher concentrations. 5alpha-Reduction also plays a role in the action of other steroid hormones, including the plant growth hormone, brassinolide, the boar pheromones, androstanol and androstenol, progesterone (in some species), and, possibly, aldosterone and cortisol. The fact that the reaction is important in plants and animals implies a fundamental role in steroid hormone action.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2001

Cervical cytology smears in sexually transmitted infection clinics in the United Kingdom.

OBJECTIVES: To determine the current practice of smear taking in sexually transmitted infection (STI) clinics within the United Kingdom; what proportion of smears are taken within the national guidelines; whether clinics are screening women not covered by the national screening programme. To compare the abnormality rates of routine and opportunistic (that is, in addition to the screening recommendations) smears; the abnormality rates of smears taken within STI clinics with those taken within the community setting. METHODS: A questionnaire was circulated to all clinics in May 1998. Details of screening practice were requested. The clinics then prospectively collected details of patient's age, GP registration, date and result of previous smear, and current result of all smears taken between 11 May 1998 and 25 May 1998. RESULTS: There were 1828 smears taken in the 2 week period; 504 (27.6%) were opportunistic. Opportunistic smears had marginal significantly increased rates of low grade abnormalities but lower (but not statistically significant) high grade abnormalities than in routine smears. 231 (12.6%) of the women were not registered with a GP so would not be included in the national programme. The national rates of abnormalities were significantly higher in the STI clinics compared with the community setting. CONCLUSION: The majority of smears taken within STI clinics fall within the national guidelines, and 12.6% of the women would probably not otherwise have been screened. The rates of abnormality were significantly higher in the STI clinics but smears taken opportunisticly were less likely to have high grade abnormalities. There is no evidence from this study to support the practice of additional smears in the presence of an effective national cytology screening programme.

Adolescent↗
PubMed2001

Management of epididymo-orchitis in Genitourinary Medicine clinics in the United Kingdom's North Thames region 2000.

A questionnaire survey and case notes audit reviewing management of epididymo-orchitis (E-O) by 34 Genitourinary Medicine (GUM) clinics located in the North Thames was undertaken. Twenty-two clinics (65%) returned completed questionnaires and audited a total of 83 newly diagnosed cases. All participating clinics offer microscopy of urethral smears and screening for Neisseria gonorrhoeae and Chlamydia trachomatis to all patients, regardless of age. However, greater numbers of clinics would offer routine microbiology of mid-stream urine (MSU) samples (20/22, 91% versus 16/22, 73%) and scrotal ultrasound (5/22, 23% versus 1/22, 5%) to patients aged over 35, compared with men under 35. Half of the cases audited were due either to sexually transmitted infections (STIs) (41/83, 49%), or associated with ascending urinary tract infections (4/83, 5%). No obvious infectious cause was identified for 38/83 cases (46%). Reported management was appropriate for the causative conditions diagnosed and accorded with the UK National Guidelines for this and related conditions.

Adult↗
PubMed2001

Factors involved in clearance of genital warts.

Consecutive patients with first presentation of external anogenital warts had the location, duration at presentation, number of warts and wart area, age, smoking and sun bed use, and presence of coexistent sexually transmitted infections (STIs) recorded. The number of treatment episodes, and number of weeks, to clear the warts were documented. Number of warts and wart area at presentation were associated with time and number of treatments to clear. Those with 1-3 warts required significantly fewer treatment episodes and less time to clear than those with 11-41 warts, as did those with warts area 2-19 mm(2) compared with wart area 100-1038 mm(2). Using survival analysis, the number of warts was significant for the number of treatments and weeks to clear. The hazard ratio for clearance with double the number of warts after 4 treatments was 0.53 (95% confidence interval [CI] 0.37-0.76), and at 4 weeks was 0.70 (0.45-0.86). The clearance rates in non-smokers compared with smokers were higher, but not significantly different. Wart burden at presentation is an indicator of time to clearance. The number of warts is the best predictor - fewer warts results in earlier clearance.

Adolescent↗
PubMed2000

Prostate formation in a marsupial is mediated by the testicular androgen 5 alpha-androstane-3 alpha,17 beta-diol.

Development of the male urogenital tract in mammals is mediated by testicular androgens. It has been tacitly assumed that testosterone acts through its intracellular metabolite dihydrotestosterone (DHT) to mediate this process, but levels of these androgens are not sexually dimorphic in plasma at the time of prostate development. Here we show that the 3 alpha-reduced derivative of DHT, 5 alpha-androstane-3 alpha,17 beta-diol (5 alpha-adiol), is formed in testes of tammar wallaby pouch young and is higher in male than in female plasma in this species during early sexual differentiation. Administration of 5 alpha-adiol caused formation of prostatic buds in female wallaby pouch young, and in tissue minces of urogenital sinus and urogenital tubercle radioactive 5 alpha-adiol was converted to DHT, suggesting that circulating 5 alpha-adiol acts through DHT in target tissues. We conclude that circulating 5 alpha-adiol is a key hormone in male development.

Androstane-3,17-diol↗
PubMed2000

Loss of CD4+ T cell proliferative ability but not loss of human immunodeficiency virus type 1 specificity equates with progression to disease.

In this study, we compared human immunodeficiency virus (HIV) type 1-specific proliferative responses with HIV-1-induced intracellular cytokine production in a cohort of clinically nonprogressing patients and individuals with progressive HIV-1 infection. We found strong HIV-1-specific proliferative responses in the clinical nonprogressor cohort that correlated with significant numbers of circulating HIV-1-specific CD4(+) T cells. In contrast, HIV-1-specific proliferative responses were absent in most individuals with progressive HIV-1 infection, even though interferon-gamma-producing HIV-1-specific CD4(+) T cells were detectable by flow cytometry. The implication of these data is that the important dysfunction seen in most HIV-positive patients from very early in disease may be an inability of HIV-1-specific CD4(+) memory T cells to proliferate in response to HIV antigens rather than an absolute loss of circulating virus-specific CD4(+) T cells.

Antigens, Viral↗
PubMed2000

Prognostic significance of p53 nuclear accumulation in localized prostate cancer treated with radical prostatectomy.

The role of p53 in the pathogenesis of, and as a predictive biomarker for, localized prostate cancer (PCa) is contested. Recent work has suggested that patterns of p53 nuclear accumulation determined by immunohistochemistry are prognostic, whereas studies using other methods question the role of p53 mutations in predicting outcome. We studied 263 men with localized PCa treated with radical prostatectomy to determine whether p53 nuclear accumulation predicts relapse and disease-specific mortality. We combined two p53 immunohistochemistry scoring systems: (a) percentage of p53-positive tumor nuclei in all major foci of cancer within the prostate; and (b) clustering, where the presence of 12 or more p53-positive cells within a x 200 power field was deemed "cluster positive." Analysis was undertaken using chi2, Kruskal-Wallis, and Mann-Whitney tests for clinicopathological variables and the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression modeling for evaluation of contribution to relapse and disease-specific survival. At mean follow-up of 55.1 months (range, 4.9-123.0 months), 39% (102 of 263) of patients had relapsed and 2.3% (6 of 253) had died of PCa. Pretreatment serum prostate-specific antigen concentration, pathological tumor stage, lymph node involvement, Gleason score, and p53 nuclear accumulation, as determined by either percentage score or cluster status, were independent predictors of relapse in multivariate analysis. Clustering of p53-positive cells distinguished between favorable and poor prognosis patients within the lowest p53-positive stratum (>0 to <2%) and was the most discriminatory threshold for predicting relapse in the entire cohort. p53 status predicted outcome in patients with a Gleason score of 5 and above but not those with a score of 4 and below. In patients treated with neoadjuvant hormonal therapy, p53 cluster positivity carried a 90% (19 of 21) risk of relapse by 36 months. All six patients who died from PCa in the period of the study exhibited p53 nuclear accumulation in 20% or more tumor nuclei. This study demonstrates strong relationships between p53 nuclear accumulation and relapse and disease-specific mortality in a large series of localized PCas. Furthermore, the presence of clusters of p53-positive nuclei delineates a group of patients with poor prognosis not identified by traditional scoring methods and supports the hypothesis that p53 dysfunction within PCa may exist in foci of tumor cells that are clonally expanded in metastases.

Aged↗
PubMed2000

Direct visualization of HIV-1-specific cytotoxic T lymphocytes during primary infection.

OBJECTIVE: HIV-specific cytotoxic T lymphocytes (CTL) are believed to play an important role in containing viral replication throughout HIV-1 infection. Previous studies have attempted to quantify the HIV-1-specific CTL precursor frequency during primary HIV infection by using limiting dilution analysis, which almost certainly underestimates the true CTL frequency. Here we use a relatively new technique to quantify HIV-specific CD8 T cells in primary HIV infection. METHODS: We have used soluble tetrameric complexes of HLA class I molecules complexed with HIV epitope peptides to study the dynamics and frequency of HIV-specific CD8 T cells in relation to plasma viral load in early HIV infection, in three patients with a highly focused HIV-specific CTL response. RESULTS: We show that the frequencies of HIV-1-specific CD8 T cells in acute infection are significantly higher than previously documented and can be demonstrated well before full seroconversion. These studies also confirm the immunodominance of the B27-restricted response in HIV infection and demonstrate a close temporal relationship between the numbers of circulating HIV-specific CD8 T cells and viral load. CONCLUSIONS: These findings strongly suggest that HIV-1-specific CD8 T cells are responding directly to the level of viral replication in early HIV infection and are a major factor in its control. In addition, the data indicate that immunodominance for CD8 T-cell responses is established in the acute phase of HIV infection.

Adult↗
PubMed2000

Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase 3 deficiency. Diagnosis, psychological evaluation, and management.

Ten male pseudohermaphrodites with 17 beta-hydroxysteroid dehydrogenase 3 (17 beta-HSD3) deficiency were evaluated in 1 clinic with an average follow-up of 10.1 years. The diagnoses were made by demonstrating low to normal serum testosterone levels, high androstenedione levels, and high ratios of serum androstenedione to testosterone in the basal state or after treatment with human chorionic gonadotropin. The molecular features of the underlying mutations were identified in all 7 families. Two additional males in the same families are believed to be affected on the basis of history obtained from family members. All of the 46,XY individuals in these families were registered at birth and raised as females (despite the presence of ambiguous genitalia in all or most), and all virilized after the time of expected puberty due to a rise in serum testosterone to or toward the normal male range. The age at diagnosis varied from 4 to 37 years. Ten individuals were studied by the same psychologist, and change of gender role (social sex) from female to male occurred in 3 subjects and in the 2 presumed affected subjects not studied. The individual with the highest serum testosterone level maintained female sexual identity, and in 2 families some of the affected males changed gender role and others did not. Thus, while androgen action plays a role in the process, additional undefined psychological, social, and/or biologic factors must be determinants of gender identity/role behavior. Management of the 7 individuals who chose to maintain female sex roles included castration, clitoroplasty, vaginal enlargement procedures when appropriate, treatment of hirsutism, cricoid cartilage reduction, and estrogen replacement. Three of the 7 are married (2 twice), 1 is involved in a long-term heterosexual relationship, 1 is engaged to be married, and the other 2 are not married and not believed to be sexually active. The 3 subjects who changed gender role behavior to male underwent hypospadias repair, and 1 was given supplemental testosterone therapy. One of these men is divorced, and the other 2 (aged 29 and 35 years) are unmarried. The diagnosis in 8 of these subjects was made after the time of expected puberty; it is unclear whether the functional and social outcomes would have been different if the diagnosis had been made and therapy begun earlier in life.

17-Hydroxysteroid Dehydrogenases↗