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Biomedical subjects

S Bullock

Publications and source records attributed to S Bullock.

At least 19 recordsLinked to original sources
PubMed2005

Modelling the evolution of genetic regulatory networks.

An evolutionary model of genetic regulatory networks is developed, based on a model of network encoding and dynamics called the Artificial Genome (AG). This model derives a number of specific genes and their interactions from a string of (initially random) bases in an idealized manner analogous to that employed by natural DNA. The gene expression dynamics are determined by updating the gene network as if it were a simple Boolean network. The generic behaviour of the AG model is investigated in detail. In particular, we explore the characteristic network topologies generated by the model, their dynamical behaviours, and the typical variance of network connectivities and network structures. These properties are demonstrated to agree with a probabilistic analysis of the model, and the typical network structures generated by the model are shown to lie between those of random networks and scale-free networks in terms of their degree distribution. Evolutionary processes are simulated using a genetic algorithm, with selection acting on a range of properties from gene number and degree of connectivity through periodic behaviour to specific patterns of gene expression. The evolvability of increasingly complex patterns of gene expression is examined in detail. When a degree of redundancy is introduced, the average number of generations required to evolve given targets is reduced, but limits on evolution of complex gene expression patterns remain. In addition, cyclic gene expression patterns with periods that are multiples of shorter expression patterns are shown to be inherently easier to evolve than others. Constraints imposed by the template-matching nature of the AG model generate similar biases towards such expression patterns in networks in initial populations, in addition to the somewhat scale-free nature of these networks. The significance of these results on current understanding of biological evolution is discussed.

Algorithms↗
PubMed2004

ATM polymorphisms as risk factors for prostate cancer development.

The risk of prostate cancer is known to be elevated in carriers of germline mutations in BRCA2, and possibly also in carriers of BRCA1 and CHEK2 mutations. These genes are components of the ATM-dependent DNA damage signalling pathways. To evaluate the hypothesis that variants in ATM itself might be associated with prostate cancer risk, we genotyped five ATM variants in DNA from 637 prostate cancer patients and 445 controls with no family history of cancer. No significant differences in the frequency of the variant alleles at 5557G>A (D1853N), 5558A>T (D1853V), ivs38-8t>c and ivs38-15g>c were found between the cases and controls. The 3161G (P1054R) variant allele was, however, significantly associated with an increased risk of developing prostate cancer (any G vs CC OR 2.13, 95% CI 1.17-3.87, P=0.016). A lymphoblastoid cell line carrying both the 3161G and the 2572C (858L) variant in the homozygote state shows a cell cycle progression profile after exposure to ionising radiation that is significantly different to that seen in cell lines carrying a wild-type ATM gene. These results provide evidence that the presence of common variants in the ATM gene, may confer an altered cellular phenotype, and that the ATM 3161C>G variant might be associated with prostate cancer risk.

Adult↗
PubMed2002

CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours.

We have recently shown that the CHEK2*1100delC mutation acts as a low penetrance breast cancer susceptibility allele. To investigate if other CHEK2 variants confer an increased risk of breast cancer, we have screened an affected individual with breast cancer from 68 breast cancer families. Five of these individuals were found to harbour germline variants in CHEK2. Three carried the 1100delC variant (4%). One of these three individuals also carried the missense variant, Arg180His. In the other two individuals, missense variants, Arg117Gly and Arg137Gln, were identified. These two missense variants reside within the Forkhead-associated domain of CHEK2, which is important for the function of the expressed protein. None of these missense variants were present in 300 healthy controls. Microdissected tumours with a germline mutation showed loss of the mutant allele suggesting a mechanism for tumorigenesis other than a loss of the wild type allele. This study provides further evidence that sequence variation in CHEK2 is associated with an increased risk of breast cancer, and implies that tumorigenesis in association with CHEK2 mutations does not involve loss of the wild type allele.

Adult↗
PubMed2001

Rb dephosphorylation and suppression of E2F activity in human breast tumor cells exposed to a pharmacological concentration of estradiol.

This report characterizes the influence of a pharmacological concentration of estradiol on growth arrest and cell death in MCF-7 breast tumor cells, with a focus on elements of the Rb-E2F cell-cycle regulatory pathway. Continuous exposure of MCF-7 breast tumor cells to 100 microM estradiol produces a marked reduction in the G1 and S phase populations and a corresponding increase in the G2/M population within 24 h; after 48 h, accumulation of cells in G1 becomes evident while after 72 h the cells appear to be equally distributed between the G1 and G2/M phases. The accumulation of cells in G1 is temporally associated with dephosphorylation of the Rb protein and suppression of E2F activity. Estradiol also produces an initial burst of cell death with loss of approximately 40% of the tumor cell population within 24 h; however, there is no tangible evidence for the occurrence of apoptosis based on terminal transferase end-labeling of DNA, DNA fragmentation analysis by alkaline unwinding, cell-cycle analysis or cell morphology. In addition to the lack of caspase-3 in MCF-7 cells, the absence of apoptosis could be related, at least in part, to the fact that estradiol promotes a rapid reduction in levels of the E2F-1 and Myc proteins. Overall, these studies are consistent with the concept that alterations in the levels and/or activity of the E2F family of proteins as well as proteins interacting with the E2F family may influence the nature of the antiproliferative and cytotoxic responses of the breast tumor cell.

Apoptosis↗
PubMed2001

The effect of season and vitamin D supplementation on bone mineral density in healthy women: a double-masked crossover study.

Vitamin D status is known to be an important determinant of bone mineral density (BMD). There is a significant seasonal variation in serum vitamin D, and some studies have reported an associated seasonal variation in BMD. The present study was devised to investigate whether a seasonal variation in BMD could be detected in healthy normal subjects, along with associated variations in serum parathyroid hormone (PTH), intestinal calcium absorption and biochemical markers of bone turnover. A second aim was to investigate whether, if such variations were identified, they could be suppressed by vitamin D supplementation. The subjects were 70 healthy female volunteers (mean age 47.2 years, range 24-70 years) recruited into a double-masked crossover study and followed over 2 years. During the first year 35 subjects received a daily oral supplement containing 800 IU (20 micrograms) cholecalciferol (group 1) and 35 subjects received a placebo preparation (group 2). During the second year the treatment each group received was reversed. Lumbar spine (L1-L4), left proximal femur and total body BMD were measured by DXA at 3-month intervals. Serum 25-hydroxyvitamin D (25-OHD), serum PTH, bone markers (bone-specific ALP (BSAP) and urinary crosslinks (DYPD/creatinine)) and calcium absorption were also measured at each visit. Cholecalciferol treatment increased serum 25-OHD by 25.4 nmol/l (p < 0.001), while a reciprocal decrease in serum PTH of 6.6 ng/l (p = 0.011) was seen in subjects in the lowest quartile of baseline serum 25-OHD. The treatment had no significant effect on spine, femur or total body BMD, calcium absorption or bone markers. When Fourier analysis was used to analyze the data for seasonal effect (defined as twice the amplitude of the 1-year period variation) a highly significant effect for 25-OHD of 18 nmol/l (p < 0.001) was found. However, no effect was found for BMD, PTH, calcium absorption or bone markers. The analysis set a 95% confidence limit to the seasonal effect of less than 0.6% for spine, total hip and total body BMD. It was concluded that in the population of healthy women studied there was no evidence of seasonal variation in spine, femur or total body BMD, serum PTH, calcium absorption or bone markers. Vitamin D supplementation was found to have no effect on BMD.

Adult↗
PubMed1999

Surface Science of a Filled Polydimethylsiloxane-Based Alkoxysilane-Cured Elastomer: RTV11.

Characterization of a filled polydimethylsiloxane (PDMS)-based elastomer, RTV11, is reported. Included in this work is resin characterization, kinetics of cure as a function of catalyst concentration, and surface properties of pristine and water-aged films. X-ray spectroscopy for chemical analysis (ESCA), dynamic contact angle (DCA) analysis, and ATR-IR were used to characterize cured films. ESCA reveals C and Si peaks in ratios expected for PDMS, but CaCO3 which comprises 32% of the bulk is not detected. The surface of cured RTV11 films is thus predominantly a PDMS network crosslinked by a siliceous domain, the latter comprising about 1.3% by weight. The presence of Ca was confirmed by energy dispersive X-ray analysis (EDX) which probes at micron depth. Stability of films in water was evaluated by tapping mode atomic force microscopy (TM-AFM), mass loss, changes in contact angles, ESCA, and optical microscopy. TM-AFM images of films aged in water for three months show an increase in surface roughness due to the formation of micro-pits which occupy about 4% of the surface. Gravimetric analysis showed fully cured films lose mass at a rate of about 0.09%/wk over a three month period in water. The mass loss associated with pitting/surface roughening comprises only 0.85% of that measured gravimetrically and by analysis of immersion water. Analysis of Si and Ca in the storage water was performed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) in order to quantify the products of surface erosion. An unexpected finding was the surface depletion-limited loss of CaCO3 during the first two months of immersion. The results of surface analytical studies are discussed in the context of the use of alkoxysilane cured PDMS resins for nontoxic fouling release applications. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

A computer-assisted learning program in pharmacology: integrating scientific and nursing knowledge.

The integration of nursing and scientific knowledge presents challenges to students grappling with the difficulties encountered in learning pharmacology. This paper outlines a collaborative project developed to assist undergraduate nursing students to learn and understand pharmacology. The innovative approach taken included the development of a CD-ROM incorporating clinical scenarios and animated graphics, with an accompanying teaching guide.

Attitude of Health Personnel↗
PubMed1997

Abbreviated educational session improves cranial computed tomography scan interpretations by emergency physicians.

STUDY OBJECTIVE: Previously published research (phase I) demonstrated a concerning misinterpretation rate of cranial computed tomography (CT) scans by emergency physicians. This study (phase II) determined whether an abbreviated educational session would improve emergency physician interpretation skills of cranial CT scans. METHODS: Participants in this prospective, interventional study in a county hospital ED were patients undergoing cranial CT scanning during ED evaluations and attending level emergency physicians. An abbreviated educational session on cranial CT interpretation skills was given to the same attending emergency physicians who participated in phase I. The educational session included basic CT interpretation skills and misinterpreted CT scans from phase I. We determined the postsession accuracy rate of the emergency physicians on 324 ED patient CT scans. The CT interpretation accuracy rates were then compared between phase I and phase II to determine the effectiveness of the educational session. RESULTS: The radiology/ED CT scan concordance rate improved from 61.3% (kappa = .22) to 88.6% (kappa = .70; P < .0001). Potentially clinically significant CT scan misinterpretations decreased from 24.1% to 4.0% (P < .0001). Most importantly, major missed findings on CT scans decreased from 11.4% to 2.8% (P < .0001). Continuous quality improvement monitoring found no instance of clinically significant patient mismanagement. CONCLUSION: Within the limits of this study, we conclude that emergency physicians' interpretation skills of cranial CT scans may be improved using a 1-hour educational session.

Brain Diseases↗
PubMed1997

Fragile X syndrome is less common than previously estimated.

In 1986, a population study of school children in the city of Coventry gave an overall prevalence in males and females for fragile X syndrome of 1/952. The 29 children diagnosed as having fragile X syndrome in this study have been re-evaluated with molecular diagnostic techniques. Eighteen of the original 29 children have been found not to have the expansion of the FMR1 gene associated with fragile X syndrome. Revised prevalence figures have been calculated giving rise to an overall prevalence figure of 1/2720 (range 1/2198-1/3089). If the four children lost to follow up are also assumed not to have the fragile X syndrome, the revised prevalence figure was 1/5714 (range 1/4762-1/6349). Clinical review of boys with severe mental retardation from this and a subsidiary study show that the clinical features of head circumference greater than the 50th centile, testicular volume greater than the 50th centile, and IQ between 35 and 70 remain helpful in distinguishing boys with fragile X syndrome from those who have non-specific mental retardation.

Adolescent↗
PubMed1996

Combined cardiac marker approach with adjunct two-dimensional echocardiography to diagnose acute myocardial infarction in the emergency department.

STUDY OBJECTIVE: To evaluate a combined cardiac marker approach with adjunct two-dimensional echocardiography in diagnosing acute myocardial infarction (AMI) in the emergency department. METHODS: This prospective, cohort study enrolled 190 patients aged 18 years and older who presented to the ED of a county teaching hospital and were admitted with chest pain suggestive of AMI. A standardized history and physical examination were performed. Serum sampling for myoglobin and creatine kinase-MB (CK-MB) was done at the time of presentation (time 0) and 3 hours later (time 3 hours). An echocardiographic study was obtained, and a left ventricular wall motion score was derived. RESULTS: Using World Health Organization criteria, 21 patients (11.2%) with AMI were identified. The serum markers were found to be clinically and statistically different between AMI and non-AMI groups at both time 0 and time 3 hours. Receiver operator characteristic curves were used to determine a "positive" myoglobin level at 88.7 ng/mL or higher at either time point, and a "positive" CK-MB level at 11.9 ng/mL or higher; these were used as the optimal cutoff values to predict AMI in the ED. Serum myoglobin was a more sensitive marker (90.5%) than CK-MB (81.0%). However, CK-MB was more specific (99.4%) than myoglobin (88.4%). A combination of both tests, which was rated positive if either test was positive, was a superior predictor overall, with a 100% capture rate of AMI patients and a 91.2% specificity. No significant difference in echocardiographic scores was appreciated in the AMI group compared with the non-AMI group (16.9 +/- 1.5 versus 15.3 +/- .5, respectively; P = .3252). CONCLUSION: Serum myoglobin shows greater sensitivity but is less specific than CK-MB in the early detection of AMI. Use of a combination of both rapid assays during a 3-hour time period in the ED appears to be superior to use of either enzyme assay alone. Two-dimensional echocardiography does not appear to be helpful in diagnosing AMI in the ED.

Aged↗
PubMed1996

Current status of tumescent liposuction in the United States. National survey results.

BACKGROUND: Tumescent liposuction is an extremely safe method of liposuction that can be performed entirely under local anesthesia. OBJECTIVE: To determine evolving trends in the current practice of tumescent liposuction in 15,336 patients treated by 66 dermatologic surgeons. METHODS: A survey questionnaire was sent to 1,778 Fellows of the American Society for Dermatologic Surgery in February 1994. The comprehensive questionnaire requested information on the number of patients treated with tumescent liposuction, complications, and various practice issues. RESULTS: Sixty-six dermatologic surgeons provided data on 15,336 patients; 44,014 body areas were treated. The complications that developed were infrequent and minor and have been reported previously. The average amount of fat removed per patient was 1,276 cc. An average of 33 cc of blood was lost per patient per procedure. Cannulas of 4.0 mm or less in diameter were commonly used. The abdomen and outer thighs were the most common areas treated in women. The flanks/love handles and abdomen were the most common areas treated in men. Intraoperative monitoring of vital signs was common. CONCLUSIONS: Tumescent liposuction is an evolving technique that has virtually eliminated blood transfusions and the major complications of liposuction under general anesthesia. Large amounts of fat can be removed using small diameter cannulas. The fat can be safely removed with a minimum risk of minor complications.

Abdomen↗
PubMed1995

Characterisation of antibodies specific for chick brain neural cell adhesion molecules which cause amnesia for a passive avoidance task.

Antisera were prepared against six postsynaptic density glycoprotein fractions (150-180, 62-80, 50, 41, 33, and 28 kDa) that show enhanced fucosylation during memory formation after training day-old chicks in a one-trial passive avoidance task. Each antiserum was tested for its possible effect on memory retention. Bilateral intracranial injections of two of the antisera, R-1 and R-6, or their IgGs (IgG-1 and IgG-6), resulted in amnesia for the passive avoidance task when chicks were tested 24 h later, IgG-1 and IgG-6 antibodies were amnestic only when injected 5.5 h after training, and had no effect when injections were made 30 min before training, thus resembling an effect previously observed with polyclonal or monoclonal anti-N-CAM antibodies. IgG-1 and IgG-6 antibodies were found to be specific for protein epitopes of glycoproteins that contain a high amount of N-linked mannose and fucose, and a very low amount of polysialic acid and O-linked galactose. Absorption of IgG-6 antibodies with neural cell adhesion molecule (N-CAM) isolated from synaptic plasma membranes derived from day-old chick brain resulted in loss of amnestic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Amnesia↗
PubMed1995

Safety of tumescent liposuction in 15,336 patients. National survey results.

BACKGROUND: Tumescent liposuction is a new method of liposuction under local anesthesia that has been developed by dermatologic surgeons. OBJECTIVE: To determine the safety of tumescent liposuction in a large group of patients treated by dermatologic surgeons. METHODS: A survey questionnaire was sent to 1,778 Fellows of the American Society for Dermatologic Surgery in February 1994. The comprehensive questionnaire requested information on numbers of patients treated with tumescent liposuction and complications that occurred. RESULTS: Sixty-six dermatologic surgeons provided data on 15,336 patients. The complications that were reported were infrequent and minor. There were no serious complications such as death, embolism (pulmonary or fat), hypovolemic shock, perforation of peritoneum or thorax, or thrombophlebitis. Blood transfusions were not required in any of the 15,336 patients and there were no admissions to the hospital for treatment of complications. CONCLUSIONS: Tumescent liposuction is an exceptionally safe method of liposuction under local anesthesia that eliminates the necessity of general anesthesia and blood transfusions. Tumescent liposuction is safer than liposuction under general anesthesia and results in fewer complications.

Humans↗
PubMed1993

Training chicks on a passive avoidance task modulates glutamate-stimulated inositol phosphate accumulation.

The effects of glutamate, N-methyl-D-aspartate (NMDA), (+)-5-methyl-10,11-dihydro-5H-dibenzo-(a,d)-cyclo-hepten 5,10-imine maleate (MK801), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and quisqualate on the accumulation of inositol phosphates (IP) from the breakdown of phosphoinositides in vitro have been studied in tissue prisms derived from a region of the chick forebrain, the intermediate medial hyperstriatum ventrale (IMHV). In prisms from the left IMHV, glutamate stimulated IP accumulation by 10-20%, AMPA by 55% and quisqualate by 650%. These effects were more marked in the right IMHV, where AMPA stimulated IP accumulation by 157% and quisqualate by 920%. MK801 and NMDA had no significant effect on IP accumulation in either hemisphere. The left IMHV is known to be the site of a biochemical cascade resulting in synaptic remodelling following training day-old chicks on a one-trial passive avoidance task. The effect of such training was to reduce glutamate-stimulated accumulation of IP by 27% (P < 0.05) in prisms taken 30 min after training. There was no effect on prisms taken at 5 or 180 min after training, and no effect at any time in the right IMHV. MK801, injected intraperitoneally before training at a concentration known to produce amnesia for the passive avoidance task, abolished the training-induced decrease without itself affecting IP accumulation. Taken in conjunction with pharmacological and autoradiographic evidence, these results indicate that memory formation for the passive avoidance task involves the activation of NMDA receptor channels, but not quisqualate or AMPA receptors, in the left IMHV of the chick 30 min after training.

Animals↗
PubMed1993

Lack of clinical significance of "enzyme-only" red cell alloantibodies.

In a retrospective study on samples from 10,000 recently transfused patients, 35 samples were found to contain an antibody that reacted with ficin-treated red cells but was not demonstrable by low-ionic-strength saline solution and indirect antiglobulin test (LISS-IAT). In those 35 patients, the specificity of the antibody was such that each patient would have been transfused with antigen-negative blood had the antibody reacted in LISS-IAT. Tests on red cells from the units already transfused showed that 19 patients had among them received, by chance, 32 antigen-positive and 74 antigen-negative units. The remaining 16 patients had among them received 57 units that were, again by chance, all antigen negative. One patient given antigen-positive blood suffered a delayed transfusion reaction; in two others the antibodies became LISS-IAT active after transfusion. However, similar changes to the LISS-IAT-active state were seen with two antibodies of patients given only antigen-negative blood. Also found in the 10,000 patients were 28 clinically insignificant antibodies, 77 sera in which the antibody was too weak to identify, and 216 autoantibodies that reacted only with ficin-treated red cells. These data support a belief, generally held in the United States but not necessarily elsewhere, that the use of protease-treated red cells for routine pretransfusion tests creates far more work than the accrued benefits justify.

Clinical Enzyme Tests↗