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Biomedical subjects

L Campbell

Publications and source records attributed to L Campbell.

At least 73 records · Page 4Linked to original sources
PubMed1997

Cellular immune reactivities in women with silicone breast implants: a preliminary investigation.

BACKGROUND: Surgical implantation of silicone breast prostheses has been conducted and considered safe for over 30 years. Some implant recipients, however, complain of a group of symptoms similar to those observed in connective tissue disorders, rheumatoid arthritis, systemic lupus erythematosus, or polymyositis. To date, immunologic sequelae have not been confirmed and remain controversial. OBJECTIVE: To examine an autoimmune-like basis for the "silicone associated disease" reported by some women with silicone breast prostheses. METHODS: Proliferative responses of peripheral blood mononuclear cells against a panel of control and connective tissue proteins and to compounds common to silicone prostheses were measured in 26 women who received silicone breast implants (with implants in place an average of 166.4 [standard deviation (SD) 58.3] months), and 23 age-matched and sex-matched healthy controls. RESULTS: The frequency and intensity of cellular immune responses against collagen I, collagen III, fibrinogen, and fibronectin were significantly increased in silicone breast implant recipients versus controls. In implant subjects, the highest frequency of immune reactivity was directed against collagen I (11/26, 42%) with collagen III being the most immunostimulatory self-antigen with a mean stimulation index (SI) of 8.2 [95% confidence interval (95% CI) 3.2]. In addition, 10/26 (39%) of the implant recipients responded to more than one of the connective tissue antigens versus 0/23 (0%, P = .0007) healthy controls. Immunologic reactivities to other antigens, including silicone-based compounds, were remarkably similar. CONCLUSIONS: The identification of self-reactivity towards these connective tissue antigens may provide important information for attempts at associating silicone breast implants with disease.

Adult↗
PubMed1997

Elderly veterans receiving care at a Veterans Affairs Medical Center while enrolled in Medicare-financed HMOs. Is the taxpayer paying twice?

Elderly veterans who visit our Veterans Affairs (VA) Medical Center primary care clinic often mention they are enrolled in HMOs. Approximately 20% of patients hospitalized at our facility report health insurance coverage. Of 1,000 hospitalizations during a 6-month period in which veterans reported insurance coverage, 337 involved elderly veterans. Of these 337 hospitalizations, 218 (65%) were for 174 veterans who stated they were enrolled in a Medicare-financed HMO. The VA's Medical Care Cost Recovery Program deemed only 46 (21%) of the hospitalizations billable and received reimbursement for 20 (9%). Thus, the VA is providing costly services already paid for by the Health Care Financing Administration under prepaid capitation contracts, and recovers minimal reimbursement from the HMOs.

Aged↗
PubMed1997

Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype.

Autosomal recessive spinal muscular atrophy (SMA) is classified, on the basis of age at onset and severity, into three types: type I, severe; type II, intermediate; and type III, mild. The critical region in 5q13 contains an inverted repeat harboring several genes, including the survival motor neuron (SMN) gene, the neuronal apoptosis inhibitory protein (NAIP) gene, and the p44 gene, which encodes a transcription-factor subunit. Deletion of NAIP and p44 is observed more often in severe SMA, but there is no evidence that these genes play a role in the pathology of the disease. In > 90% of all SMA patients, exons 7 and 8 of the telomeric SMN gene (SMNtel) are not detectable, and this is also observed in some normal siblings and parents. Point mutations and gene conversions in SMNtel suggest that it plays a major role in the disease. To define a correlation between genotype and phenotype, we mapped deletions, using pulsed-field gel electrophoresis. Surprisingly, our data show that mutations in SMA types II and III, previously classed as deletions, are in fact due to gene-conversion events in which SMNtel is replaced by its centromeric counterpart, SMNcen. This results in a greater number of SMNcen copies in type II and type III patients compared with type I patients and enables a genotype/phenotype correlation to be made. We also demonstrate individual DNA-content variations of several hundred kilobases, even in a relatively isolated population from Finland. This explains why no consensus map of this region has been produced. This DNA variation may be due to a midisatellite repeat array, which would promote the observed high deletion and gene-conversion rate.

Centromere↗
PubMed1997

Diversity of the ribulose bisphosphate carboxylase/oxygenase form I gene (rbcL) in natural phytoplankton communities.

The phytoplankton of the world's oceans play an integral part in global carbon cycling and food webs by conversion of carbon dioxide into organic carbon. They accomplish this task through the action of the Calvin cycle enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). Here we have investigated the phylogenetic diversity in the form I rbcL locus in natural phytoplankton communities of the open ocean and representative clones of marine autotrophic picoplankton by mRNA or DNA amplification and sequencing of a 480 to 483 bp internal fragment of this gene. Five gene sequences were recovered from nucleic acids of natural phytoplankton communities of the Gulf of Mexico. The rbcL genes of two Prochlorococcus isolates and one Synechococcus strain (WH8007) were also sequenced. Sequences were aligned with the database of rbcL genes and subjected to both neighbor-joining and parsimony analyses. The five sequences from the natural phytoplankton community spanned nearly the entire diversity of characterized form I rbcL genes, with some sequences closely related to isolates such as Synechococcus and Prochlorococcus (forms IA and I) and prymnesiophyte algae (form ID), while other sequences were deeply rooted. Unexpectedly, the deep euphotic zone contained an organism that possesses a transcriptionally active rbcL gene closely related to that of a recently characterized manganese-oxidizing bacterium, suggesting that such chemoautotrophs may contribute to the diversity of carbon-fixing organisms in the marine euphotic zone.

Amino Acid Sequence↗
PubMed1997

In vivo analysis of DNA-protein interactions on the human erythropoietin enhancer.

The erythropoietin (EPO) gene is one of the best examples of a mammalian gene controlled by oxygen tension. The DNA elements responsible for hypoxia-induced transcription consist of a short region of the proximal promoter and a <50-bp 3' enhancer. The elements act cooperatively to increase the transcriptional initiation rate approximately 100-fold in response to low oxygen tension in Hep3B cells. Two distinct types of transactivating proteins have been demonstrated to bind the response elements in the human EPO enhancer in vitro: one shows hypoxia-inducible DNA binding activity, while the other activity binds DNA under normoxic and hypoxic conditions. We have investigated the DNA-protein interactions on the human EPO enhancer in living tissue culture cells that produce EPO in a regulated fashion (Hep3B) and in cells that do not express EPO under any conditions tested (HeLa). We have identified in vivo DNA-protein interactions on the control elements in the human EPO enhancer by ligation-mediated PCR technology. We show that the putative protein binding sites in the EPO enhancer are occupied in vivo under conditions of normoxia, hypoxia, and cobalt exposure in EPO-producing cells. These sites are not occupied in cells that do not produce EPO. We also provide evidence for a conformational change in the topography of the EPO enhancer in response to hypoxia and cobalt exposure.

Base Sequence↗
PubMed1997

How long should suction drains stay in after breast surgery with axillary dissection?

Daily suction drainage volumes were recorded for 63 patients after wide local excision of a breast carcinoma with axillary dissection (n = 37) or mastectomy with axillary dissection (n = 26). Suction drains were removed at the discretion of the clinical ward staff after a median of 4 days (range 1-7 days). In all, 32 patients (51%) later developed seromas requiring needle aspiration. Minor wound infection rate was not significantly higher in patients who developed seromas than those who did not (5 vs 2). Seroma formation was associated with a larger total suction drain volume (mean 480 ml (range 28-1150 ml) vs 240 ml (range 10-635 ml); P = 0.0001). The median yield of axillary lymph nodes was significantly greater in those who developed seromas (11 (range 4-20) vs 8 (range 1-19); P = 0.002). There was no difference in the volume drained in the 24 h preceding drain removal (mean 60 ml (range 0-150 ml) vs 50 ml (range 0-290 ml); NS). Keeping drains in situ longer did not protect against seroma formation. By 48 h, 74% of the total volume drained by each drain had been collected. Seroma formation after breast surgery with axillary dissection is an inconvenience for a high proportion of patients. This complication does not seem to be reduced by prolonged suction drainage of the wound, which in itself delays patient discharge and causes further inconvenience.

Axilla↗
PubMed1997

Psychometric evaluation of the Organizational Job Satisfaction Scale.

Findings are reported from a replicated evaluation of the psychometric properties of the Organizational Job Satisfaction Scale. Data lend strong support for the scale which assesses four dimensions of organizational job satisfaction. Principal component factor analysis of data from two independent samples of urban staff registered nurses (RNs) (n = 496; n = 532) confirmed four dimensions of pay, interaction, administration, and status. Cronbach's alpha for subscales ranged from .76 to .88. Pearson correlation coefficients for the interrelationships among subscales and an estimate of theta verified internal consistency. The Organizational Job Satisfaction Scale scores correlated significantly with a criterion measure of job enjoyment. Hypothesis testing of theoretically predictable relationships supported construct validity. Scores on the organizational job satisfaction subscales correlated significantly with automony, stress, and commitment. Item revisions and recommendations for future use of the instrument are discussed.

Adult↗
PubMed1996

p53 N-terminus-targeted protein kinase activity is stimulated in response to wild type p53 and DNA damage.

The p53 tumour suppressor protein plays a central role in the cellular defence against agents which cause genetic damage. The activity of p53 is regulated at different levels and is subject to multi-site phosphorylation by a variety of different protein kinases. In this paper we have characterised p53 N-terminus-targeted protein kinase (p53NK) activities, present in a range of cell lines, following fractionation of cellular lysates by ion exchange chromatography on HiTrap Q and Mono Q resins. Three peaks of p53NK activity were observed following fractionation of HeLa cell lysates; these activities were each able to catalyse phosphorylation of up to three residues (serines 4, 6 and 9 in murine p53) within the N-terminus of the p53 protein. Similarly, multiple p53NK activities were detected in the MethAp53(ts) cell line (which expresses the valine 135 temperature-sensitive p53 protein). Strikingly, when these cells were shifted from 38 degrees C (the non-permissive temperature) to 28 degrees C, at which the p53 adopts a wild type conformation, a fivefold stimulation of kinase activity was detected. Moreover, when the DNA damage-inducing drugs etoposide or camptothecin were added to the cells, a further stimulation of kinase activity was observed following growth at 28 degrees C, but not 38 degrees C. These data are consistent with a regulatory model in which p53 is sensitive to stress or DNA damage through phosphorylation at its N-terminus.

Animals↗
PubMed1996

A prospective audit of wound infection rates after caesarean section in five West Yorkshire hospitals.

A three month prospective audit of wound infection following emergency and elective caesarean section was carried out in five West Yorkshire hospitals. Among 4076 women undergoing delivery in the five obstetric departments, the caesarean rate was 15.4%. The overall infection rate was 45/628 (7.2%) with a range of 2.5-17.2% between the five centres. The infection rate was 14/226 (6.2%) when antibiotics were used compared with 31/402 (7.7%) without antibiotics. The use of prophylactic antibiotics made no significant difference to the infection rate, which did not correlate with duration of labour or of ruptured membranes. The number of vaginal examinations correlated with the infection rate. In conclusion, the caesarean section rate observed was higher than that estimated for the UK as a whole, but was distorted by one centre with a high rate. For the other four hospitals the caesarean rate was unexceptional. The ratio of emergency to elective operations was comparable with recently reported values in the UK and the wound infection rate was within the widely varying limits found in previous studies. In view of the relatively low infection rate recorded without antibiotics, in the interests of cost effectiveness, prophylaxis may be limited in future to selected women at high risk. Because this was an audit rather than a randomized study we cannot exclude that this is already happening on an empirical basis.

Antibiotic Prophylaxis↗
PubMed1996

Inheritance of chromosome 7 is associated with a drug-resistant phenotype in somatic cell hybrids.

A major form of drug resistance in tumour cells known as classical multidrug resistance (MDR) is associated with the overexpression of the mdr1 gene product, the membrane protein P-glycoprotein (P-gp), which acts as an energy-dependent drug efflux pump. In this study the inheritance of P-gp expression was examined using hybrids formed after somatic cell fusion between a drug-sensitive human T-cell leukaemia cell line, CEM/CCRF, and a drug-resistant derivative, CEM/A7, which is characterized by a clonal chromosomal duplication dup(7)(q11.23q31.2). Fourteen hybrids, chosen at random, were analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) and by binding studies involving the monoclonal antibody MRK16, which recognises an external P-gp epitope. Only two hybrids were positive for both MRK16 antibody labelling and mdr1 mRNA. Partial karyotypic analysis of all hybrids revealed that only the MRK16-positive hybrids contained the duplication in chromosome 7 seen in the CEM/A7 parental MDR line. Therefore, P-gp overexpression in the MRK16-positive hybrids may be linked to the inheritance of chromosome 7 from CEM/A7 and possibly associated with the chromosome 7 abnormality.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Accelerated telomere shortening in ataxia telangiectasia.

Ataxia telangiectasia (AT) is characterized by neurological deterioration, immunodeficiency, spontaneous chromosomal instability, hypersensitivity to ionizing radiation, predisposition to cancer, particularly T cell leukaemia and lymphoma, and premature ageing. The most commonly observed defect affecting telomeres in humans is telomeric fusions, particularly in T lymphocytes in AT patients. Rarely, some tumour cells, like senescent cells, have dicentric chromosomes that may arise as a result of telomeric sequence loss. We show that the AT mutation in the homozygous state confers a predisposition to accelerated telomere shortening with increasing age in peripheral blood lymphocytes (PBLs), which may be linked to premature senescence. We also show that telomeric fusions are associated with large (> 90%) preleukaemic translocation clones in T cells. We propose that these fusions may result from a compound effect of accelerated telomere shortening, together with a growth advantage of cells in large clones which leads to further telomere loss. Fusions are not observed in leukaemic cells in these patients. There is no evidence that either accelerated telomere loss per se or telomeric fusions are important in tumourigenesis. Telomerase is present in both normal and AT lymphocytes and so neither telomere shortening nor telomeric fusions can be explained by the absence of telomerase.

Adolescent↗
PubMed1996

Actual versus self-reported cognitive dysfunction in HIV-1 infection: memory-metamemory dissociations.

The relationship between subjective awareness and objective neuropsychological status in HIV-1 infection remains unclear. Forty-six HIV-1 seropositive males were administered a battery of neuropsychological measures assessing episodic memory, metacognition, and depression. Results of ANOVA revealed a dissociation between subjects' self-complaint of neuropsychological impairment and objective performance, with subjects who denied cognitive impairment performing worse on memory testing. Three subgroups were identified: A group whose self-reported cognitive impairment exceeded deficits demonstrated on memory testing (37% of subjects); a group who denied impairment but evidenced deficits on memory testing (26% of subjects); and a group whose self-appraisal was consistent with performance (37% of subjects). These data suggest that self-report of cognitive dysfunction among HIV-1 infected subjects is frequently at variance with objective neuropsychological testing and that diminished awareness of decline among medically symptomatic HIV-1 infected subjects can be identified.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Methylphenidate slows right hemisphere processing in children with attention-deficit/hyperactivity disorder.

To examine the effects and particularly, any potential detrimental effects of methylphenidate on right hemisphere processing in children with attention-deficit/hyperactivity disorder (ADHD), the performance of 26 children (aged 8-15 years) with ADHD was compared under methylphenidate and placebo on various cognitive tasks in a double-blind within-subjects design. Results indicated that reaction times on a tachistoscopic task were slower on methylphenidate for stimuli that produced a left visual field advantage (reflecting better right hemisphere functioning) but not for stimuli that produced a right visual field advantage (reflecting better left hemisphere functioning) or for bilateral stimuli. It is argued that methylphenidate induces a slower response on tasks involving right hemisphere processing, resulting in slower reaction times and unchanged accuracy rates. Findings on two tasks that more closely reflect classroom-type tasks revealed an improvement in performance on methylphenidate, suggesting that any stimulant-induced benefits on learning style may have overcome detrimental effects on unilateral processing. These findings may help understand the complex, diverse, and sometimes unpredictable effects of psychostimulants on cognitive functioning that are observed clinically in individuals treated for ADHD.

Adolescent↗
PubMed1996

Improved detection of disseminated pheochromocytoma using post therapy I-131 MIBG scanning.

A 50-year-old man had metastatic pheochromocytoma to the left frontal bone. The primary adrenal tumor was removed 12 years previously. Bone scanning and diagnostic I-131 and I-123 MIBG imaging showed metastatic lesions in the right femur and midthoracic spine. However, post-therapy I-131 MIBG scanning showed extensive and widespread metastatic disease. Post-therapeutic I-131 MIBG whole-body scanning was necessary to more fully assess the extent of metastatic pheochromocytoma.

3-Iodobenzylguanidine↗