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Biomedical subjects

M Campbell

Publications and source records attributed to M Campbell.

At least 343 records · Page 19Linked to original sources
PubMed1993

Conditional expression and oncogenicity of c-myc linked to a CD2 gene dominant control region.

Over-expression of the c-myc gene is widely implicated in the genesis of lymphoid neoplasia, including tumours of the T-cell lineage. To study the effects of deregulated c-myc expression on T-cell development and oncogenesis, we sought to generate a transgenic mouse model in which c-myc expression was targeted specifically to the T-cell lineage. A plasmid construct containing a dominant control region (DCR) from the human CD2 locus linked 5' to the human c-myc gene was used to generate 2 lines of transgenic mice. Both strains developed thymic lymphoma at low frequency, but thymic development and peripheral T-cell numbers were otherwise apparently normal. Low tumour penetrance was consistent with the observed lack of stable CD2-myc transgene mRNA in tissues of healthy transgenic mice. In contrast, transgene RNA was detected in all malignant tumours as well as in early lymphomatous lesions. RNase protection analyses confirmed these findings and showed that the PI human c-myc promoter was active in all neoplastic tissues but not in the thymus or other tissues of healthy transgenic mice. Despite the low spontaneous tumour incidence, the presence of the transgene markedly and uniformly accelerated the onset of tumours after neonatal infection with Moloney murine leukaemia virus. All tumours were rearranged for T-cell receptor beta-chain genes and were of T-cell origin from their surface phenotype (Thy-1+, CD3+, CD4+/-, CD8+, sIg-). Virus-accelerated tumours contained clonal integrations of Moloney murine leukaemia virus, suggesting that proviral insertional mutagenesis may have played a role in tumour development. Analysis of several candidate myc-cooperating genes failed to reveal any rearrangements apart from a low frequency involving proviral insertion at the pim-1 locus. The CD2-myc mouse should therefore be a valuable system in screening for novel myc-collaborating genes involved in T-cell lymphoma.

Animals↗
PubMed1993

Inhibition of Rev-mediated HIV-1 expression by an RNA binding protein encoded by the interferon-inducible 9-27 gene.

Interferon inhibits expression of human immunodeficiency virus type-1 (HIV-1) through unknown mechanisms. A gene inducible by interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma) was isolated by screening of a human complementary DNA library for proteins binding to the Rev-responsive element (RRE) of HIV-1. The product of this gene, RBP9-27, was shown to bind RNA in vitro and to inhibit HIV-1 expression after transfection into human cells. RBP9-27 primarily inhibited Rev-dependent posttranscriptional steps of viral gene expression. Thus, RBP9-27 is a cellular factor that antagonizes Rev function. These results suggest an interferon-induced antiviral mechanism operating through the induction of RNA binding proteins such as RBP9-27. Elucidation of RBP9-27 function may lead to a better understanding of the mechanism of interferon action during HIV-1 infection.

Amino Acid Sequence↗
PubMed1993

Sexual preference assessment of sexual aggressors: predictors of penile response magnitude.

A current method used to assess the sexual preference of sexual aggressors is the recording of their penile responses during the presentation of erotic stimuli. This method is ineffective in subjects who do not obtain sufficient penile responses. Whether variables related either to the subjects or their crimes would correlate with the magnitude of penile responses during sexual preference assessment was studied. The penile responses of 92 subjects were recorded. Older and pre-sentencing subjects showed a lower maximum penile response magnitude than younger and sentenced subjects. Results are discussed as they relate to the validity of physiological assessment of sexual preference.

Adolescent↗
PubMed1993

Acute dystonic reaction with low-dose pimozide.

It is essential to recognize individual susceptibility to neuroleptic-induced side effects for treatment guidelines. This paper reports on a 6.9-year-old autistic male who developed repeated episodes of acute dystonic reactions associated with pimozide administration at the doses of 0.096 mg/kg/day and 0.032 mg/kg/day and 32 hours following pimozide withdrawal, as well as during subsequent thioridazine administration. It draws the clinician's attention to unusual susceptibility to extrapyramidal side effects and suggests that if a child shows this type of susceptibility to one neuroleptic, he/she may react similarly to other neuroleptics as well.

Autistic Disorder↗
PubMed1993

Naltrexone in autistic children: behavioral symptoms and attentional learning.

OBJECTIVE: To assess critically the short-term efficacy and safety of naltrexone in autistic children and its effects on discrimination learning in the laboratory. METHOD: A parallel group design was employed. After a 2-week placebo baseline period, children were randomly assigned either to naltrexone or to placebo for a period of 3 weeks followed by a one-week posttreatment placebo period. Multiple raters and rating scales were employed in a variety of conditions. Forty-one children, all inpatients, ages 2.9 to 7.8 years, completed the study. Naltrexone reduced hyperactivity and had no effect on discrimination learning in the laboratory. There was a suggestion that it had a beneficial effect on decreasing self-injurious behavior. Untoward effects were mild and transient. CONCLUSION: In the present study, naltrexone significantly reduced only hyperactivity, and no serious untoward effects were observed. The effectiveness of naltrexone in the treatment of autism and self-injurious behavior requires additional assessment in a sample of children with moderate to severe self-injurious behavior.

Attention↗
PubMed1993

Phenytoin prophylaxis in severe pre-eclampsia and eclampsia.

OBJECTIVE: To determine plasma phenytoin levels and seizure outcome in women given phenytoin for seizure prophylaxis in severe pre-eclampsia and eclampsia. DESIGN: Prospective observational study comparing two phenytoin loading regimens. SETTING: Two UK teaching hospitals. SUBJECTS: Sixty-seven consecutive women with severe pre-eclampsia and five with eclampsia. INTERVENTIONS: The first 29 women were given a 15 mg/kg intravenous loading dose of phenytoin. The next 43 received 17.5 mg/kg. All were given 500 mg phenytoin 12 h after completion of the loading dose and then 250 mg every 12 h for four doses. MAIN OUTCOME MEASURES: Total plasma phenytoin levels at 30 min, 6 h and 12 h after loading dose, 6 h after first maintenance dose and on days 2 and 3 of maintenance therapy; eclamptic seizures after starting phenytoin. RESULTS: Mean plasma phenytoin levels were higher at 30 min and 6 h after the 17.5 mg/kg loading dose. Nine of 29 (31%) phenytoin levels 30 min after the loading dose were above the therapeutic range in the 15 mg/kg group compared with 26/38 (68%) in the 17.5 mg/kg group (P < 0.01). Six of 27 (22%) phenytoin levels 12 h after the loading dose were subtherapeutic in the 15 mg/kg group compared with 2/38 (5%) in the 17.5 mg/kg group (P < 0.05). Three women, two in the 17.5 mg/kg group, developed seizures after starting phenytoin. All three had plasma levels within the therapeutic range. CONCLUSIONS: Compared with a loading dose of 17.5 mg/kg, loading with 15 mg/kg phenytoin was associated with a lower incidence of high plasma levels at 30 min but a higher incidence of subtherapeutic levels at 12 h. Seizures occur in 2 to 3% of pre-eclamptics despite apparently therapeutic phenytoin levels.

Adult↗
PubMed1993

What is vestibular papillomatosis? A study of its prevalence, aetiology and natural history.

OBJECTIVES: To clarify the prevalence, aetiology, symptoms and natural history of vestibular papillomatosis. DESIGN: Study in two parts: 1. prevalence assessed by colposcopic examination of the vulva of unselected patients by one doctor (J.M.W.); 2. patients selected by clinical appearance as having vestibular papillomatosis (by J.M.W. and other doctors) assessed in a research clinic. SETTING: Outpatient genitourinary medicine clinic in South London. SUBJECTS: Part 1 study: 295 female clinic attenders; part 2 study: 18 women with clinical vestibular papillomatosis. MAIN OUTCOME MEASURES: Part 1 study: number of unselected patients found to have vestibular papillomatosis. Part 2 study: associated symptoms, histology, DNA hybridisation and polymerase chain reaction on vulval biopsies. Clinical regression of lesions. Cervical cytology and colposcopy. RESULTS: Part 1 study: Vestibular papillomatosis was identified by colposcopic examination of the vulva in 3/295 (1%) of women. Part 2 study: 9/18 (50%) women with vestibular papillomatosis were asymptomatic; the other nine had intermittent mild symptoms. Thirteen (72%) had a history of genital warts. Vulval biopsies had features suggestive of wart virus infection on histology in 17/18 (94%) and HPV16 was found by DNA hybridisation studies or polymerase chain reaction in 7/18 (39%). On follow up (mean duration 9 months) the vulval lesions had regressed in 9/12 patients. Ten patients had cervical wart virus infection or intraepithelial neoplasia (CIN), or both, and five needed laser treatment for this. CONCLUSIONS: In this study vestibular papillomatosis was associated with human papillomavirus (HPV) infection. This study suggests that vestibular papillomatosis need not be treated, but patients with it may be at increased risk for CIN.

Adolescent↗
PubMed1993

Pharmacoeconomics of nonsteroidal anti-inflammatory drugs (NSAIDs).

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the relief of the symptoms of osteoarthritis (OA), rheumatoid arthritis (RA), sprains and strains, sports injuries and menstrual disorders, and have a small role in the management of patent ductus arteriosus in the neonate. In patients with RA, symptom relief through use of NSAIDs is firmly established, although it remains unclear whether they influence the course and outcome of the disease. For the average patient with RA taking NSAIDs, the attributable risk of hospitalisation with gastrointestinal problems related to NSAIDs is 1.3 to 1.6% annually and risk of death is 0.15%. Associations of therapy with risk are greatest with age, corticosteroid use and previous NSAID-related gastrointestinal adverse effects, and less marked with disability and high NSAID dose. These are important data in attempting to balance risk of therapy with clinical efficacy in an individual patient, and assessing the cost-effectiveness of prophylaxis. Although half of all NSAID consumption is for control of pain associated with degenerative conditions, their superiority over simple analgesics in osteoarthritis is poorly documented. This finding supports the use of the simple analgesic paracetamol (acetaminophen) as the preferred therapy of osteoarthritis, especially when its lower cost and low incidence of adverse effects are taken into consideration. Consistent differences in clinical effectiveness of individual NSAIDs have not been demonstrated, although unpredictable interpatient variation in response to individual agents is of considerable clinical importance, and a more expensive NSAID may prove cost effective for some patients. Cost effectiveness can be improved by a self-adjusted dosage regime which also leads to lower overall drug consumption. The adverse gastrointestinal effects of these drugs account for about 30% of the overall cost of arthritis treatment, and although studies to date have been too limited to assess the relative risk of gastrointestinal toxicity of the different NSAIDs reliably, ibuprofen appears to be one of the least hazardous, and azapropazone one of the most hazardous. Although the effectiveness of prophylaxis with H 2-antagonists and with prostaglandin E 1 analogues (prostaglandin-E 1 analogues) has been established, estimates of cost-benefit ratios are widely divergent. To establish the most cost-effective therapy with NSAIDs, more data are required to establish multivariable risk profiles for identification of patients at particular risk, the optimal drug, and its optimal dosage and duration of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Inflammatory Agents, Non-Steroidal↗