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Biomedical subjects

J Bell

Publications and source records attributed to J Bell.

At least 235 records · Page 13Linked to original sources

Identification of a CA repeat at the TCRA locus using yeast artificial chromosomes: a general method for generating highly polymorphic markers at chosen loci.

The creation of a comprehensive genetic map in human has been limited by the lack of highly polymorphic markers spaced evenly throughout the human genome. We have utilized yeast artificial chromosomes (YAC) containing large human DNA inserts to help identify highly polymorphic (CA)n repeats at a chosen locus. The DNA of a YAC containing the locus was subcloned in M13 vectors, and the recombinants were screened at high stringency to detect preferentially long (CA)n repeats (n greater than 20). These repeats, which are the most likely to be highly polymorphic, were then studied to confirm both the level of polymorphism and their precise genetic location. This strategy has permitted the identification of a new, highly polymorphic CA repeat (77% heterozygosity) at the T cell receptor alpha chain (TCRA) locus on chromosome 14q. It provides a powerful marker for assessing the role of this locus in the susceptibility to autoimmune and infectious diseases. This approach should permit the development of highly polymorphic markers at any targeted locus and rapidly improve the current human genetic map.

Base Sequence↗

P-glycoprotein expression in locally advanced breast cancer treated by neoadjuvant chemotherapy.

Using immunohistochemistry and the monoclonal antibody C219 we have investigated P-glycoprotein expression in 26 locally advanced breast cancers. Twenty four patients had received four cycles of chemotherapy (mitozantrone, mitomycin-C and methotrexate) prior to mastectomy; two received tamoxifen. Twelve tumours exhibited an objective response to the chemotherapy. A background pattern of isolated weakly positive (1+) stromal staining (myofibroblast) was observed in seven tumours, two of which had been treated by tamoxifen alone. Two of the tumours treated by induction chemotherapy showed positive staining (1+) within a very small number of isolated tumour cells (maximum of three) and macrophages. The significance of this staining is not clear although C219 may simply be cross reacting with myosin. We have failed to demonstrate a clear clinical utility for C219 in breast cancer, particularly regarding the identification of patients in whom MDR chemotherapy be avoided once metastases develop.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

In search of a discourse on aging: the elderly on television.

This article analyzes the images of aging presented in five of the prime-time television programs of 1989 most watched by the elderly: Murder, She Wrote, The Golden Girls, Matlock, Jake and the Fatman, and In the Heat of the Night, all of which have central elderly characters. An examination of the title sequences reveals that earlier television stereotypes of the elderly "as more comical, stubborn, eccentric, and foolish than other characters" have been replaced by more positive stereotypes of them as powerful, affluent, healthy, active, admired, and sexy.

Aged↗

T-cell receptors and rheumatic disease: approaches to repertoire analysis.

T-lymphocytes are thought to play a major role in the pathogenesis of a number of autoimmune rheumatic diseases. Techniques have recently been developed to study the T-cell receptor (TCR) usage of individual T-cells, and are likely to give major insight into the pathogenesis of rheumatic diseases. We describe the development of the TCR repertoire and the techniques available to study it. There is evidence that germline TCR complex polymorphisms may contribute to genetic susceptibility to rheumatoid arthritis. A number of studies have looked at rheumatoid synovial T-lymphocytes, some of which have found restricted TCR usage.

Animals↗

Routine diagnosis of mammary Paget's disease. A modern approach.

This study compares the diagnostic reliability of conventional mucin histochemistry and immunocytochemical techniques in distinguishing mammary Paget's disease from superficial spreading malignant melanoma and primary intraepidermal carcinoma. Formalin-fixed, paraffin-embedded archival tissue was used and comprised 13 cases of mammary Paget's disease, five cases of superficial spreading melanoma, and six cases of intraepidermal carcinoma. Sections from each case were stained for the presence of mucin using diastase periodic-acid-Schiff (d-PAS) with and without an alcian blue counterstain as well as immunocytochemistry for cytokeratin (CAM 5.2), epithelial membrane antigen (NCRC-11) and c-erb B-2 (21N). Mucin staining in intraepidermal carcinoma and malignant melanoma was consistently negative. Diastase-resistant PAS positivity was seen in six of 13 cases of mammary Paget's disease and eight of 13 cases using an alcian blue counterstain. NCRC-11 showed positive immunoreactivity in four of six cases of intraepidermal carcinoma, one in five cases of melanoma, and five of 13 cases of mammary Paget's disease. Positive immunoreactivity using CAM 5.2 and 21N was seen in all cases of mammary Paget's disease, with consistent negative immunoreactivity in the other tumor types. We conclude that CAM 5.2 and 21N should be used in the investigation of mammary Paget's disease in preference to conventional mucin stains.

Antibodies, Monoclonal↗

Changes in criminal activity after entering methadone maintenance.

The impact of different approaches to methadone maintenance on the level of crime committed by heroin addicts was examined in a cohort of addicts entering methadone treatment. The cohort comprises three groups: 72 subjects (group 1) who were approved for treatment and referred to a long-term programme which tolerated continued illicit drug use in treatment; 159 subjects (group 2) who were referred to an abstinence orientated programme from which clients who continued to use heroin were expelled; and 84 subjects who were rejected as unsuitable or failed to complete the assessment process. Official records of convictions were used to calculate conviction rates in the pre- and post-assessment periods. Differences between groups in conviction rates for drug and property crimes were analysed using Poisson regression. Three variables--age, sex and age of first criminal conviction--were significant predictors of conviction rates and all analyses controlled for these variables. Most of the rejected subjects entered treatment during the study period and it was, therefore, not possible to interpret differences between treated and untreated subjects. Among those who entered treatment, property offence rates actually rose, due to a significant increase in conviction rates in group 2. Subjects in group 1 were retained significantly longer in treatment than those in group 2. Among those who remained in treatment less than 12 months, most offences occurred after leaving treatment. When conviction rates were adjusted for time spent in treatment, the differences between the clinics disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Who should receive methadone maintenance?

The aim of this study was to evaluate the assessment policies of a regional unit established to process requests for entry to several long-term methadone maintenance programmes. The factors which led staff to reject an applicants request for methadone maintenance were retrospectively analysed from assessment records. Analysis indicated that the decision to reject applicants had been based on the judgement that they were not physically dependent on opioids; other factors favouring rejection included less involvement in crime, youth, and short duration of drug use. Eighty-four applicants who had either been rejected (n = 58) or failed to complete the assessment (n = 26) were followed. At follow-up, more than half of the subjects had entered methadone programmes, usually after a long delay. Four subjects had achieved a degree of stable abstinence. The remainder were continuing to use illicit drugs, or were in treatment or prison. Four subjects had died. We conclude that: (1) our criteria for excluding people from treatment were based on the perceived need to keep non-addicted people from maintenance treatment; and (2) such a policy in practice served to prolong the applicants' illicit drug use and delay their entry to treatment.

Adult↗

Treatment dependence: preliminary description of yet another syndrome.

The last decade has witnessed an expansion of treatment services and research into alcoholism and addiction. As so often happens when attempting to find solutions to pressing individual and social problems, the solutions have come to acquire an importance of their own, obscuring the problems they were intended to solve. Many programmes are characterized by stereotyped approaches to treatment, which seem more in line with the needs of the staff than with the problems of the clients. The hopes that treatment for addictions will solve some of the problems of contemporary society have given treatment a salience which cannot be justified in terms of results. Frustrated at the results of treatment, clinic staff intensify their efforts and attribute the shortcomings of treatment to a lack of client motivation. There are disconcerting parallels between these behaviours in clinicians and the behavioural changes of the Alcohol Dependence Syndrome. The label 'Treatment dependence syndrome' is proposed to characterize a pattern of individual and institutional behaviour which is both self-perpetuating and self-defeating.

Alcoholism↗

Advanced glycosylation end products in the mesenteric artery.

We measured advanced glycosylation end products in the mesenteric artery of 37 patients (ages 29-82 years), 34 of whom were nondiabetic. Samples of arterial tissue were obtained during bowel resectioning. Advanced glycosylation end products were measured as collagen-linked fluorescence (excitation wavelength 370 nm, emission wavelength 440 nm) after collagenase digestion of tissue samples. Mean fluorescence of the arterial samples was 15 U/mg (range 5.3-27). Collagen fluorescence correlated with patients' age (r = 0.57; P less than 0.001). No difference in the collagen-linked fluorescence was observed between men and women (P = 0.63), hypertensive and normotensive patients (P = 0.44), smokers and nonsmokers (P = -0.52), and patients with and without symptomatic coronary heart disease (P = 0.7). This study demonstrates, for the first time, the relationship between collagen-linked fluorescence and patients' age in human arterial tissue ex vivo.

Adult↗

Methadone dosage and retention of patients in maintenance treatment.

Retention of patients in methadone treatment was studied in a cohort of 238 heroin addicts who entered maintenance programmes between February 1986 and August 1987. All subjects had been assessed at a centralised unit and referred to one of two other units for maintenance. Of the ten client characteristics that we analysed, three--a history of imprisonment, a history of dependence on barbiturates or benzodiazepines and employment status at entry--were included with "clinic" and maximum dose of methadone in the Cox regression models. Allowing for the other four variables, the maximum daily dose of methadone dispensed during the study period was a highly significant predictor of retention (P less than 0.00001). With maximum dose stratified into three levels--less than 60 mg, 60-79 mg, 80+ mg--and with the lowest stratum used as the baseline, the relative risk (RR) of leaving treatment was halved (RR 0.47, 95% confidence interval [CI] 0.33-0.67) for subjects receiving 60-79 mg, and halved again (RR 0.21, 95% CI 0.12-0.38) for those who received 80+ mg. Clinic dosage policies contribute significantly to retention in methadone maintenance treatment. Clinics need to develop dosage policies in negotiation with individual patients.

Actuarial Analysis↗

Hypothalamic or central obesity is associated with an early rise in plasma insulin concentration.

Insulin levels in a 7-year-old boy with hyperphagia and obesity following an episode of meningoencephalitis were studied sequentially during the course of progressive weight gain. High fasting insulin levels (1183 pmol/L) and strikingly high insulin release in response to glucose (7892 pmol/L) were found within weeks of the onset of the illness. The abnormality in insulin secretion occurred prior to the marked weight gain. Hyperinsulinemia was not accompanied by hypoglycemia. Early hyperinsulinemia may be a primary event in the development of hyperphagia and obesity following hypothalamic injury.

Child↗

Occult regional lymph node metastases from breast carcinoma: immunohistological detection with antibodies CAM 5.2 and NCRC-11.

Ninety-eight consecutive patients with primary operable breast cancer and an initial diagnosis of no regional lymph node metastases as assessed by conventional light microscopy were studied. Immunohistological staining of routine lymph node sections was assessed using two monoclonal antibodies: CAM 5.2 (Becton Dickinson) with specificity for low molecular weight cytokeratin, and NCRC-11 (CRC Laboratories, Nottingham) with specificity for epithelial mucin antigen. Positive staining for occult metastases was seen in nine patients with CAM 5.2 and in eight of these nine with NCRC-11. At a follow-up out to 14 years, there was no difference in overall survival, in recurrence-free survival, or in frequency of or time to presentation of local or regional recurrences between occult metastasis-positive and occult metastasis-negative patients. This study concludes that while immunohistological staining of routine lymph node sections increases the diagnostic yield of metastases, it is not to be recommended as this increase is of no useful clinical value.

Adenocarcinoma↗