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S Parsons

Publications and source records attributed to S Parsons.

At least 19 recordsLinked to original sources

Softening constraints in constraint-based protein topology prediction.

This paper is concerned with the handling of uncertain data about the applicability of constraints in protein topology prediction. It discusses the use of novel methods of representing and reasoning with uncertain data, and presents the results of some experiments in using these methods to build probabilistic models of constraint application. It thus builds on work by other authors in both constraint satisfaction and probabilistic reasoning.

Models, Molecular

Routine prophylactic vena cava filter insertion in severely injured trauma patients decreases the incidence of pulmonary embolism.

BACKGROUND: Trauma patients are at increased risk for venous thromboembolism despite routine prophylaxis. A five-year retrospective review of pulmonary embolism at the Medical Center Hospital of Vermont showed that four types of injuries (head injuries, spinal cord injuries, complex pelvic fractures, and hip fractures) accounted for 92 percent of pulmonary emboli in patients on the trauma service. STUDY DESIGN: Beginning July 1991, all patients who met criteria for a high-risk injury (excluding hip fractures) had prophylactic vena cava filters inserted percutaneously in the radiology suite. Weekly impedance plethysmography was performed for the detection of deep vein thrombosis. Following discharge, abdominal duplex ultrasound was performed at one month, six months, and yearly to check filter position and patency. RESULTS: To date, a total of 63 patients, or 2 percent of the total trauma population, had prophylactic vena cava filters inserted. There were 19 (30 percent) deep vein thromboses in this population of patients and one patient had a pulmonary embolism (1.5 percent). Overall there was significant (chi-square, p < 0.00072) reduction of pulmonary embolism on the trauma service compared to the historical controls. Follow-up examination with abdominal duplex ultrasound showed a 30-day patency rate of 100 percent and a one- and two-year patency rate of 96.1 +/- 3.8 percent by life-table analysis. CONCLUSIONS: We concluded that prophylactic vena cava filters are efficacious in decreasing the risk of pulmonary embolism in high-risk trauma patients.

Adult

Tyrosine phosphorylation of protein phosphatase 2A in response to growth stimulation and v-src transformation of fibroblasts.

The catalytic subunit of protein phosphatase 2A (PP2A) is inactivated by in vitro phosphorylation of Tyr307 by receptor and nonreceptor protein tyrosine kinases (Chen, J., Martin, B. L., and Brautigan, D. L. (1992) Science 257, 1261-1264). Here we show the phosphorylation of PP2A in cells under different growth conditions. In lysates of nontransformed murine 10T1/2 fibroblasts, there were two forms of PP2A at 36 kDa detected after two-dimensional gel electrophoresis and immunoblotting with anti-PP2A peptide antibody. These two forms exactly comigrated with unphosphorylated purified PP2A and the PP2A 32P-labeled by in vitro phosphorylation with p60v-src kinase. The phosphorylated form of PP2A recovered from red blood cells or produced by in vitro phosphorylation was eliminated by incubation with tyrosine-specific phosphatase (PTP1B). Transformation of 10T1/2 cells by expression of p60v-src resulted in most of the PP2A in the cells being converted to a phosphorylated form that was reactive with anti-phosphotyrosine antibody. Serum starvation of cells reduced the amount of phosphorylated PP2A, whereas serum stimulation of quiescent cells caused an increase to the same relative amount of phosphorylated PP2A as in src-transformed cells. Addition of epidermal growth factor to quiescent NeoR cells (10T1/2 fibroblasts overexpressing epidermal growth factor receptors) temporarily increased the level of phosphorylation of PP2A, with a peak at 5-15 min and a return to basal level within 60 min. The results show that PP2A is phosphorylated in intact cells, and the extent of this modification is increased by growth factors or cell transformation, providing evidence for a physiological mechanism of PP2A regulation.

Amino Acid Sequence

Prototyping a genetics deductive database.

We are developing a laboratory notebook system known as the Genetics Deductive Database. Currently our prototype provides storage for biological facts and rules with flexible access via an interactive graphical display. We have introduced a formal basis for the representation and reasoning necessary to order genome map data and handle the uncertainty inherent in biological data. We aim to support laboratory activities by introducing an experiment planner into our prototype. The Genetics Deductive Database is built using new database technology which provides an object-oriented conceptual model, a declarative rule language, and a procedural update language. This combination of features allows the implementation of consistency maintenance, automated reasoning, and data verification.

Animals

The effect of posture and environmental temperature on cardiovascular reflexes in normal subjects and diabetes mellitus.

This study was undertaken to determine the effects of environmental temperature (17 degrees C or 27 degrees C) and posture on heart rate variability during forced sinus arrhythmia (deep breathing), and of environmental temperature on the heart rate and blood pressure responses to standing, and to the cold pressor test. A group of non-diabetic young subjects (23 +/- 5 years) and a group of older diabetic patients (54 +/- 15 years) were studied. At 27 degrees C, supine resting heart rate and systolic blood pressure were lower than at 17 degrees C in both diabetic and non-diabetic subjects, and heart rate variability was lower than at 17 degrees C in the non-diabetic subjects (p less than 0.01) with seven of 17 abnormal or borderline results (all seven subjects had normal values at 17 degrees C). Room temperature had no effect on supine heart rate variability in the diabetic patients. At 27 degrees C heart rate variability in the upright posture was significantly greater than supine (p less than 0.001) in the non-diabetic subjects. In the diabetic subjects, heart rate variability when standing at 17 degrees C increased such that five patients classified as abnormal when supine had normal values when upright. A similar pattern was observed at 27 degrees C, although only those with normal heart rate variability showed an increase on standing. Room temperature had no effect on the responses to the cold pressor test, or the blood pressure responses to standing, although the heart rate response was greater in both groups at 27 degrees C. This study shows that care should be taken to standardize the conditions under which heart rate variability is determined.

Adult

Comparison of the accuracy of glucose reflectance meters in pregnant insulin-dependent diabetics.

Home monitoring of blood glucose by reflectance meters has been shown to be accurate in the nonpregnant diabetic and is currently used for outpatient glucose control in the pregnant diabetic as well. Beckman ASTRA glucose results from samples collected into sodium fluoride were used as the standard for this study. Comparisons were then made to four glucose reflectance meters: Accu-Check II, One Touch, DiaScan S, and ExacTech. Although the reflectance meters appeared to be useful for assessing blood glucose trends in the pregnant diabetic, the results obtained from these meters would be unacceptable in the laboratory setting. Unfortunately, because of the erratic combination of proportional and constant bias, correction factors are not easily ascertained. Laboratories and physicians should reconsider the use of these reflectance meters for inpatient evaluation and general population screening of pregnant women.

Blood Glucose Self-Monitoring

Assembly of double-shelled rotaviruslike particles by simultaneous expression of recombinant VP6 and VP7 proteins.

Simultaneous coinfection of Spodoptera frugiperda cells with baculovirus recombinants containing the genes for VP6 and VP7 of bovine rotavirus strain C486 resulted in the production of spherical particles resembling smooth, double-shelled rotavirus. These particles were predominantly located in the cell culture supernatant instead of being cell associated. Pretreatment of infected-cell culture supernatants with CaCl2, prior to particle purification, was found to enhance the smooth appearance of the particles. The authenticity of the proteins making up the particles was demonstrated by their reactivity with antiserum specific for double-shelled C486 rotavirus.

Animals

Plasma histamine profiles in paediatric cardiopulmonary bypass.

We have previously reported our findings of very high plasma histamine levels in the extracorporeal blood primes of infants undergoing cardiopulmonary bypass (CPB) for correction of congenital cardiac defects and have now extended this enquiry to examine the whole peri-operative period. In this preliminary study, samples of blood for plasma histamine were drawn from a mixed group of congenital cardiac patients featuring varying degrees of cyanosis, differing hypothermic operative conditions and utilising two oxygenator systems. Despite the diversity of this group a common pattern of histamine release emerged with a clear origin at the commencement of bypass, and continuing during the operative period. Our results suggest that priming procedures using stored donor blood provide a major contributing source of histamine release with inevitable deleterious consequences to the post-operative outcome.

Cardiopulmonary Bypass

Ultrasound detection of micro-emboli in the middle cerebral artery during cardiopulmonary bypass surgery.

The occurrence of neurological sequelae following cardiopulmonary bypass (CBP) surgery has stimulated interest in refining the techniques of extracorporeal circulation. Air micro-emboli originating from the oxygenator have been postulated as one source of cerebral damage. Since controversy still exists regarding the merits of bubble versus membrane oxygenators, this has prompted investigators to devise methods to determine the amount of micro-emboli produced during CPB. In this study, 27 patients undergoing CPB surgery for coronary artery disease (21) or valve replacement (6) were examined. The surgical and anaesthetic techniques were standardised in all patients except for the type of oxygenator used. A bubble oxygenator was used in 17 patients (Bentley Bio-10, William Harvey or Dideco) and a membrane oxygenator with a 25 microns filter in the remaining 10 patients (Bentley BOS CM50). Transcranial pulsed Doppler ultrasound was used to obtain blood velocity signals from the middle cerebral artery throughout CPB. A flow disturbance index (FDI) was defined which provided a representative index of the number of micro-emboli passing the ultrasound transducer. The FDI indicated the presence of gaseous micro-emboli during insertion of the aortic cannula in 22 of the 27 patients. In the 17 patients with a bubble oxygenator, the FDI ranged from 4-39. In the 10 patients with a membrane oxygenator, the FDI was always 0. Variation of gas flow rates in 3 patients with bubble oxygenators showed a change in the FDI from 4 +/- 4 at a flow rate of 2 l/min to 17 +/- 9 at 5 l/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The effect of arterial filtration on reduction of gaseous microemboli in the middle cerebral artery during cardiopulmonary bypass.

Noninvasive in vivo detection of gaseous microemboli in the middle cerebral artery, by transcranial Doppler ultrasound, was used to determine the effect of filtration in the arterial catheter using 25- and 40-microns filters and bubble oxygenators in patients undergoing cardiopulmonary bypass surgery. Eighteen patients undergoing coronary artery bypass surgery were studied using a closed cardiac (unvented heart) model. Group 1 patients (no filters) had the highest incidence of gaseous microemboli, as indicated by the ultrasound microemboli index, at both high and low oxygen flow rates. Group 2 patients (40-microns filters) had a significantly lower microemboli index, particularly at low oxygen flow rates (t = 4.9, p less than 0.001). The 25-microns group patients had the lowest values of all. No microemboli were detected at low oxygen flow rates, and microemboli were detected in only 0.1% of the samples at high oxygen flow rates. Additionally, observations on vented hearts in 3 patients undergoing cardiac valve surgery indicate that the origin of gaseous microemboli may be air trapped inside the heart.

Cardiopulmonary Bypass

The detection of microemboli in the middle cerebral artery during cardiopulmonary bypass: a transcranial Doppler ultrasound investigation using membrane and bubble oxygenators.

Twenty-seven patients were examined who were undergoing cardiopulmonary bypass (CPB) surgery with either a bubble oxygenator or a capillary membrane oxygenator. The latter incorporated an arterial filter and bubble trap. A noninvasive Doppler ultrasound technique is described for monitoring irregularities in the Doppler flow signals attributable to gaseous microemboli detected in the middle cerebral artery during CPB. The ultrasound index for detecting gaseous microemboli (MEI) indicated the presence of such microemboli in 22 of the 27 patients during insertion of the aortic cannula. Measurements during CPB showed the MEI ranged from 4 to 39 in the 17 patients with a bubble oxygenator. However, all 10 patients with a membrane oxygenator had an MEI of 0. Varying the gas flow rates in 3 patients with bubble oxygenators showed a change in MEI from 4 +/- 4 (SD) at a flow rate of 2 L/min to 17 +/- 9 at a flow rate of 5 L/min. This observation supports the assumption that the MEI is providing quantitative information regarding the presence of gaseous emboli in the middle cerebral artery.

Cardiopulmonary Bypass

Transcranial measurement of blood velocities in the basal cerebral arteries using pulsed Doppler ultrasound: velocity as an index of flow.

Blood velocities have been measured transcranially, at small Doppler angles, in the middle cerebral artery of normal volunteers. Cerebral blood flow was changed by varying carbon dioxide tension. In four volunteers, the relationships between arterial pCO2 and percentage change in intensity weighted mean, median, and maximum Doppler-shifted frequencies in the internal carotid and middle cerebral arteries were linear with slopes of 2.5 and 2.8% per mm Hg change in pCO2. In 38 volunteers, the relationship between end-expiratory pCO2 and time-averaged maximum Doppler frequency was linear over the range of pCO2 20-60 mm Hg with slopes of 2.5 and 2.9 percentage change per mm Hg, for internal carotid and middle cerebral, respectively. These results are very similar to those reported using direct methods of measuring cerebral blood flow. As the transcranial Doppler method is reproducible, this indicates that changes in middle cerebral blood velocity may be used to monitor changes in flow.

Adult

Influence of colchicine and vinblastine on the intracellular migration of secretory and membrane glycoproteins: I. Inhibition of glycoprotein migration in various rat cell types as shown by light microscope radioautography after injection of 3H-fucose.

Previous studies have shown that colchicine and vinblastine inhibit secretion in many cell types by interrupting the normal intracellular migration of secretory products. In the present work, radioautography has been used to study the effects of these drugs on migration of membrane and secretory glycoproteins in a variety of cell types. Young (40 gm) rats were given a single intravenous injection of colchicine (4.0 mg) or vinblastine (2.0 mg). At 10 min after colchicine and 30 min after vinblastine administration, the rats were injected with 3H-fucose. Control rats received 3H-fucose only. All rats were sacrificed 90 min after 3H-fucose injection and their tissues processed for light microscope radioautography. Examination of secretory cell types such as ameloblasts and thyroid follicular cells in control animals revealed reactions of approximately equal intensity over the Golgi region and over extracellular secretion products, while in drug-treated rats most of the reaction was confined to the Golgi region. In a variety of other cell types, including endocrine cells (e.g., hepatocytes) and cells generally considered as nonsecretory (e.g., intestinal columnar cells), reaction in control animals occurred both over the Golgi region and over various portions of the cell surface. In drug-treated animals, a strong Golgi reaction was present, but reaction over the cell surface was weak or absent. These results indicate that in many cell types, colchicine and vinblastine inhibit migration out of the Golgi region not only of secretory glycoproteins, but also of membrane glycoproteins destined for the plasma membrane.

Animals

Influence of colchicine and vinblastine on the intracellular migration of secretory and membrane glycoproteins: III. Inhibition of intracellular migration of membrane glycoproteins in rat intestinal columnar cells and hepatocytes as visualized by light and electron-microscope radioautography after 3H-fucose injection.

In the first paper of this series (Bennett et al., 1984), light-microscope radioautographic studies showed that colchicine or vinblastine inhibited intracellular migration of glycoproteins out of the Golgi region in a variety of cell types. In the present work, the effects of these drugs on migration of membrane glycoproteins have been examined at the ultrastructural level in duodenal villous columnar cells and hepatocytes. Young (40 gm) rats were given a single intravenous injection of colchicine (4.0 mg) or vinblastine (2.0 mg). At 10 min after colchicine and 30 min after vinblastine administration, the rats were injected with 3H-fucose. Control rats received 3H-fucose only. All rats were sacrificed 90 min after 3H-fucose injection and their tissues processed for radioautography. In duodenal villous columnar cells, 3H-fucose labeling of the apical plasma membrane was reduced by 51% after colchicine and by 67% after vinblastine treatment; but there was little change in labeling of the lateral plasma membrane. Labeling of the Golgi apparatus increased. This suggests that labeled glycoproteins destined for the apical plasma membrane were inhibited from leaving the Golgi region, while migration to the lateral plasma membrane was not impaired. In hepatocytes, labeling of the sinusoidal plasma membrane was reduced by 83% after colchicine and by 85% after vinblastine treatment. Labeling of the lateral plasma membrane also decreased, although not so dramatically. Labeling of the Golgi apparatus and neighboring secretory vesicles increased. This indicates that the drugs inhibited migration of membrane glycoproteins from the Golgi region to the various portions of the plasma membrane. Accumulation of secretory vesicles at the sinusoidal front suggests that exocytosis may also have been partially inhibited. In both cell types, microtubules almost completely disappeared after drug treatment. Microtubules may, therefore, be necessary for intracellular transport of membrane glycoproteins, although the possibility of a direct action of these drugs on Golgi or plasma membranes must also be considered.

Animals

DNA repair in cultured keratinocytes.

Most of our understanding of DNA repair mechanisms in human cells has come from the study of these processes in cultured fibroblasts. The unique properties of keratinocytes and their pattern of terminal differentiation led us to a comparative examination of their DNA repair properties. We have examined the relative repair capabilities of the basal cells and the differentiated epidermal keratinocytes as well as possible correlations of DNA repair capacity with respect to age of the donor. In addition, since portions of human skin are chronically exposed to sunlight, we have assessed the repair response to ultraviolet (UV) irradiation (254 nm) when the cells are conditioned by chronic low-level UV irradiation. The methods of Liu and Karasek were used to grow pure keratinocytes on collagen gels following their isolation from abdominal skin of newborns and adults at autopsy. Density labeling with 5-bromodeoxyuridine was used to resolve repair replication from the semiconservative mode. We found similar repair characteristics in human epidermal keratinocytes to those previously reported for cultured fibroblasts. However, the DNA repair response in basal cells was much greater than that in differentiated cells from the same skin preparation. Our comparative studies of DNA repair in keratinocytes from infant and aged donors have revealed no significant age-related differences for repair of UV-induced damage to DNA. Sublethal UV conditioning of cells from infant skin had no appreciable effect on either the repair or normal replication response to higher, challenge doses of UVL. However, such conditioning resulted in attenuated repair in keratinocytes from adult skin after UV doses above 25 J/m2. In addition, a surprising enhancement in replication was seen in conditioned cells from adult following challenge UV doses.

Cell Differentiation

A nosocomial outbreak of diarrheal disease due to Yersinia enterocolitica serotype 0:5, biotype 1.

An outbreak of diarrheal disease due to Yersinia enterocolitica serotype 0:5 , biotype 1, involved nine hospitalized patients. The possible source of this infection was two patients who were both hospitalized with a history of several weeks of intermittent diarrhea. Person-to-person contact was the probable mode of transmission of the disease. The present report describes the second known nosocomial outbreak of infection due to Y. enterocolitica, Serotype 0:5 of Y. enterocolitica is not commonly encountered, and its involvement in an outbreak of gastroenteritis has not been previously reported. The importance of the enrichment technique in the isolation of Y. enterocolitica is demonstrated.

Adult