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W A Phillips

Publications and source records attributed to W A Phillips.

At least 37 records · Page 2Linked to original sources
PubMed1999

Lipopolysaccharide-induced priming of the human neutrophil is not associated with a change in phosphotyrosine phosphatase activity.

The activation of the neutrophil respiratory burst is a two-step process involving an initial 'priming' phase followed by a 'triggering' event. The biochemical mechanisms which underlie these events are yet to be fully elucidated, but the evidence suggests a crucial role for stimulus-induced tyrosine phosphorylation. The enhanced tyrosine phosphorylation observed upon triggering primed cells may reflect an increase in tyrosine kinase activity or a reduction in the levels of the opposing phosphotyrosine phosphatases (PTPases). We have investigated the latter by examining the possibility that lipopolysaccharide (LPS)-induced priming of the neutrophil respiratory burst involves the suppression of cellular PTPase activity. Purified human neutrophils were incubated for 60 min with and without LPS. Priming of the respiratory burst was confirmed by fMet-Leu-Phe-induced cytochrome c reduction. The level of PTPase activity was assessed by dephosphorylation of [32P]RR-src peptide as substrate. Pretreatment of human neutrophils with 200 ng/ml LPS induced a 2.9 +/- 0.3 (mean +/- SEM, n = 3, P = 0.022) fold increase in the fMet-Leu-Phe-triggered respiratory burst. In the same cells, LPS did not induce a significant change in the total cellular PTPase activity (1.02 +/- 0.02-fold, mean +/- SEM, n = 3, P = 0.63). Similarly, stimulation of neutrophils with fMet-Leu-Phe or phorbol myristate acetate did not significantly affect the cellular PTPase activity (P = 0.94 and 0.68, respectively). Our results suggest that suppression of PTPase activity is not the mechanism underlying the priming and/or triggering of the neutrophil respiratory burst.

Dose-Response Relationship, Drug↗
PubMed1999

Activation of protein kinase C augments butyrate-induced differentiation and turnover in human colonic epithelial cells in vitro.

As the colonic epithelium is physiologically exposed to butyrate and to activators of protein kinase C, we examined the effect of the protein kinase C signalling pathway on butyrate-induced expression of markers of differentiation. Activators and inhibitors of protein kinase C were used in combination with butyrate and effects on the expression of markers of differentiation examined in colon cancer cell lines. When the protein kinase C activator phorbol myristate acetate (100 nM) was added for 24 h prior to the addition of 2 mM butyrate, there was a synergistic increase in alkaline phosphatase activity (154 +/- 11% above that for butyrate alone, P = 0.003) in a concentration- and time-dependent manner. Butyrate-induced expression of carcinoembryonic antigen and interleukin-8, dome formation and cell turnover were also markedly augmented by pre-treatment with phorbol myristate acetate. A similar effect was observed with propionate or acetate (but not other differentiating agents), when phorbol myristate acetate and butyrate were added concurrently, or when other protein kinase C activators were used. Pharmacological inhibition of protein kinase C activity did not alter butyrate-induced alkaline phosphatase activity, but abrogated the augmentation induced by phorbol myristate acetate. We conclude that protein kinase C does not mediate the differentiating effects of butyrate on colon cancer cells, but its activation regulates butyrate-induced cellular differentiation.

Apoptosis↗
PubMed1999

Postweaning performance of calves from Angus, Brahman, and reciprocal-cross cows grazing endophyte-infected tall fescue or common bermudagrass.

Data from 403 Polled Hereford-sired calves from Angus, Brahman, and reciprocal-cross cows were used to evaluate the effects of preweaning forage environment on postweaning performance. Calves were spring-born in 1991 to 1994 and managed on either endophyte-infected tall fescue (E+) or common bermudagrass (BG) during the preweaning phase. After weaning, calves were shipped to the Grazinglands Research Laboratory, El Reno, OK and stratified to one of two winter stocker treatments by breed and preweaning forage; stocker treatments were winter wheat pasture (WW) or native range plus supplemental CP (NR). Each stocker treatment was terminated in March, calves grazed cool-season grasses, and calves were then moved to a feedlot phase in June. In the feedlot phase, calves were fed to approximately 10 mm fat over the 12th rib and averaged approximately 115 d on feed. When finished, calves were weighed and shipped to Amarillo, TX for slaughter. Averaged over calf breed group, calves from E+ gained faster during the stocker phase (P<.10), had lighter starting and finished weights on feed (P< .01), lighter carcass weights (P<.01), and smaller longissimus muscle areas (P<.05) than calves from BG. Calves from E+ were similar to calves from BG in feedlot ADG, percentage kidney, heart, and pelvic fat, fat thickness over 12th rib, yield grade, marbling score, and dressing percentage. Maternal heterosis was larger in calves from E+ for starting weight on feed (P<.01), finished weight (P<.10), and carcass weight (P<.16). These data suggest that few carryover effects from tall fescue preweaning environments exist, other than lighter, but acceptable, weights through slaughter. These data further suggest that the tolerance to E+ in calves from reciprocal-cross cows, expressed in weaning weights, moderated postweaning weight differences between E+ and BG compared to similar comparisons in calves from purebred cows.

Animal Feed↗
PubMed1998

Increased levels of phosphatidylinositol 3-kinase activity in colorectal tumors.

BACKGROUND: Phosphatidylinositol 3-kinase (PI 3-kinase), an enzyme that phosphorylates inositol phospholipids at the D-3 position of the inositol ring, has been implicated in the signaling pathways regulating cell growth by virtue of its activation in response to various mitogenic stimuli. In spite of the considerable attention PI 3-kinase has received with regard to its possible role in the mitogenic pathways in hematopoietic malignancies, there are few reports of investigations into PI 3-kinase activity in solid tumors. METHODS: Colorectal tumor tissue and normal-appearing colonic mucosa from the same patients were homogenized and solubilized and adjusted to equal protein levels. PI 3-kinase then was immunoprecipitated from 200 microg of the solubilized tissue using a polyclonal antibody to the p85 subunit of PI 3-kinase. PI 3-kinase activity was assessed using phosphatidylinositol as the substrate and the assay product analyzed by thin-layer chromatography. Phosphorylation of phosphatidylinositol in the D-3 position was confirmed by high performance liquid chromatography analysis of deacylated and deglycerated products. RESULTS: Thirty-two of the 37 tumors tested (86%) demonstrated increased PI 3-kinase activity compared with normal-appearing mucosa from the same patients (overall mean increase+/-standard error of the mean=3.8+/-0.6-fold; P < 0.05, Student's t test for paired data). The frequency and extent of increased PI 3-kinase enzyme activity in tumors did not correlate with clinical parameters or the presence of oncogenic ras mutations. CONCLUSIONS: In this study colorectal tumors exhibited enhanced PI 3-kinase activity compared with normal colonic mucosa, raising the possibility that PI 3-kinase may be a potential target for new strategies for the treatment of colorectal carcinoma.

Colorectal Neoplasms↗
PubMed1997

Phosphotyrosine phosphatase activity in the macrophage is enhanced by lipopolysaccharide, tumor necrosis factor alpha, and granulocyte/macrophage-colony stimulating factor: correlation with priming of the respiratory burst.

Tyrosine phosphorylation is now recognised as a key event in the activation of the macrophage respiratory burst. Since vanadate, a phosphotyrosine phosphatase (PTP) inhibitor is able to enhance the respiratory burst, we proposed that agents which prime the macrophage for enhance respiratory burst activity may do so by suppressing cellular PTP activity. The level of PTP activity in murine bone marrow-derived macrophages (BMM) was assessed by the ability of cell lysates to dephosphorylate 32P-labelled RR-src peptide. In contrast to our hypothesis, pretreatment of BMM with bacterial lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha) or granulocyte/macrophage-colony stimulating factor (GMCSF), agents which prime for enhanced respiratory burst activity, was found to dramatically increase the level of cellular PTP activity. The time-course for this increase correlated well with the time course of priming by these agents. In addition, colony stimulating factor-1, a cytokine which does not prime the macrophage respiratory burst, did not enhance PTP levels. The physiological relevance of the increased PTP activity was further supported by confirming it was active against endogenous tyrosine phosphorylated substrates. Interestingly, phorbol myristate acetate and zymosan, agents which trigger the macrophage respiratory burst, were found to inhibit the PTP activity of BMM. Our results demonstrate the regulation of cellular PTP activity by priming agents and further highlight the importance of tyrosine phosphorylation and dephosphorylation events in the regulation of macrophage function.

Animals↗
PubMed1997

In search of common foundations for cortical computation.

It is worthwhile to search for forms of coding, processing, and learning common to various cortical regions and cognitive functions. Local cortical processors may coordinate their activity by maximizing the transmission of information coherently related to the context in which it occurs, thus forming synchronized population codes. This coordination involves contextual field (CF) connections that link processors within and between cortical regions. The effects of CF connections are distinguished from those mediating receptive field (RF) input; it is shown how CFs can guide both learning and processing without becoming confused with the transmission of RF information. Simulations explore the capabilities of networks built from local processors with both RF and CF connections. Physiological evidence for synchronization, CFs, and plasticity of the RF and CF connections is described. Coordination via CFs is related to perceptual grouping, the effects of context on contrast sensitivity, amblyopia, implicit influences of color in achromotopsia, object and word perception, and the discovery of distal environmental variables and their interactions through self-organization. Cortical computation could thus involve the flexible evaluation of relations between input signals by locally specialized but adaptive processors whose activity is dynamically associated and coordinated within and between regions through specialized contextual connections.

Cerebral Cortex↗
PubMed1997

The Northern Marshall Islands Radiological Survey: data and dose assessments.

Fallout from atmospheric nuclear tests, especially from those conducted at the Pacific Proving Grounds between 1946 and 1958, contaminated areas of the Northern Marshall Islands. A radiological survey at some Northern Marshall Islands was conducted from September through November 1978 to evaluate the extent of residual radioactive contamination. The atolls included in the Northern Marshall Islands Radiological Survey (NMIRS) were Likiep, Ailuk, Utirik, Wotho, Ujelang, Taka, Rongelap, Rongerik, Bikar, Ailinginae, and Mejit and Jemo Islands. The original test sites, Bikini and Enewetak Atolls, were also visited on the survey. An aerial survey was conducted to determine the external gamma exposure rate. Terrestrial (soil, food crops, animals, and native vegetation), cistern and well water samples, and marine (sediment, seawater, fish and clams) samples were collected to evaluate radionuclide concentrations in the atoll environment. Samples were processed and analyzed for 137Cs, 90Sr, 239+240Pu and 241Am. The dose from the ingestion pathway was calculated using the radionuclide concentration data and a diet model for local food, marine, and water consumption. The ingestion pathway contributes 70% to 90% of the estimated dose. Approximately 95% of the dose is from 137Cs. 90Sr is the second most significant radionuclide via ingestion. External gamma exposure from 137Cs accounts for about 10% to 30% of the dose. 239+240Pu and 241Am are the major contributors to dose via the inhalation pathway; however, inhalation accounts for only about 1% of the total estimated dose, based on surface soil levels and resuspension studies. All doses are computed for concentrations decay corrected to 1996. The maximum annual effective dose from manmade radionuclides at these atolls ranges from .02 mSv y(-1) to 2.1 mSv y(-1). The background dose in the Marshall Islands is estimated to be 2.4 mSv y(-1). The combined dose from both background and bomb related radionuclides ranges from slightly over 2.4 mSv y(-1) to 4.5 mSv y(-1). The 50-y integral dose ranges from 0.5 to 65 mSv.

Cesium Radioisotopes↗
PubMed1997

Frequency and clinico-pathological associations of ras mutations in colorectal cancer in the Victorian population.

BACKGROUND: Mutations in the oncogene ras occur in 20-50% of colorectal cancers. The presence of these mutations allows screening tests to be developed based on the identification of mutant DNA in cells derived from cancers. A study of the prevalence and clinicopathological associations of ras mutations was undertaken. METHODS: The frequency of mutations in codons 12 and 13 of the K-ras gene was investigated in 103 colorectal carcinomas using restriction fragment length polymorphism. RESULTS: Mutations were detected in 32% (33/103) of the tumours, predominantly in codon 12 (25/33). No mutations were detected in normal-appearing mucosa from the same patients. CONCLUSIONS: Analysis of the frequency of ras mutations compared with various independent clinical variables revealed a sex-linked relationship between the presence of a ras mutation and nodal status but no correlation with any other clinical parameter was found. The findings suggest that screening tests based on ras mutation detection may lack sensitivity because of the presence of mutations in only 32% of tumours.

Aged↗
PubMed1997

The management of acute bone loss in severe catabolism due to burn injury.

Reduced bone formation has been documented in both children and adults following burn injury of > or = 40% total body surface area. In children, reduced bone formation and hypercalciuria may be the underlying causes of acute and sustained reduction in bone mineral density. The possible consequences of this reduction are an increase in extrapolated annual fracture incidence and reduced peak bone mass. Excessive endogenous glucocorticoid production, immobilization, bone marrow suppression, and magnesium depletion are all postulated as underlying causes. The most promising potential management agent is recombinant human growth hormone, which can stimulate bone formation via production of insulin-like growth factor I(IGF-I) and its associated binding protein, IGFBP-3, which correlates with bone mineral density in adults. Long-term treatment may be necessary to see a positive effect on bone formation and bone density. Correcting any detected magnesium depletion, and exercise as tolerated, are two other management strategies that might improve bone formation in this population.

Bone Development↗
PubMed1997

Health informatics.

This article addresses health informatics and some of the technology advancements and issues facing health care organizations today. As the ability to communicate and share data with other institutions is rapidly advancing, so is the need for industry coding standardization and data protection.

Computer Communication Networks↗
PubMed1996

Measures for investigating the contextual modulation of information transmission.

The aim of this paper is to show how information theoretic measures can be used to analyse and interpret the results of psychophysical experiments designed to search for conditions under which information from one source modulates the transmission of information from another source. We therefore use measures of mutual and conditional information to analyse systems with two inputs. The information transmitted by such a system can be split into three components depending on whether it is shared between the two inputs or is specific to each. We are concerned here with distinguishing systems that use one input to modulate transmission of information about the other from systems that simply add both inputs, and show how the three components provide evidence for distinguishing between additive and modulatory effects. We also report numerical simulations of the sampling biasses and variances of these measures as a function of the sample size and propose minimum sample sizes that should be used to overcome the bias.

Journal Article↗
PubMed1996

Improving detection of pediatric elbow fractures by understanding their mechanics.

Fractures around the elbow are among the most common fractures in children, but they can also be some of the most elusive to detect. Although elbow fractures result from a variety of stresses applied to the three bones constituting the elbow joint, hyperextension-rotation injuries with valgus or varus stress are the most common cause of elbow fractures. Less common are direct impact injuries to the posterior aspect of the elbow. Because all three bones and their articulations are morphologically different, the various traumatic forces applied result in distinctly different types of fractures in each of the bones. For example, hyperextension with vertical stress produces supracondylar fractures of the distal humerus, longitudinal linear ulnar fractures, and buckle fractures; hyperextension with valgus stress causes impaction fractions of the radial head and neck, transverse olecranon fractures, and medial epicondylar fractures, whereas varus stress produces Monteggia fractures, lateral condylar avulsion fractures, transverse olecranon fractures, and longitudinal linear ulnar fractures. Understanding these forces and their effects is important because it facilitates detection of the wide variety of fractures in their more subtle forms.

Adolescent↗
PubMed1996

Slipped capital femoral epiphysis. Prediction of contralateral involvement.

We performed a retrospective review of the medical records and radiographs of fifty children who had had unilateral slipped capital femoral epiphysis. Our purpose was to determine if there were any epidemiological parameters that were associated with the later development of a contralateral slip. The mean duration of follow-up was thirty-four months (range, twenty-four to sixty-eight months). Physiological maturity, determined with a modified form of the Oxford method for assessment of bone age, strongly correlated with the risk of development of a contralateral slip in patients who were initially seen with a unilateral slip (r = 0.59, p < 0.0005). The scores were determined by four raters; the variation in the predictive value of the scores among the raters was not significant (p = 0.5). The relationship between the score as determined with the modified Oxford method and the risk of contralateral involvement had a linear distribution. The four raters performed a total of 442 observations to determine the modified Oxford scores for the fifty hips. The prevalence of a subsequent slip for the hips that had been assigned a score of 16 points was 85 +/- 15 per cent (95 per cent confidence limit) (seventeen of twenty observations). The risk of contralateral involvement when the score was 21 points was 11 +/- 9 per cent (six of fifty-four observations). A slip did not develop in any hip with a score of 22 points or more (sixty-nine observations). For boys, the age at the time of the initial slip was predictive of a contralateral slip. A contralateral slip developed in all four boys who had been eleven years and seven months old or less at the time of the initial presentation; however, a contralateral slip developed in only nine of the twenty-two boys who had been eleven years and eight months to fourteen years and eleven months old. A contralateral slip did not develop in the three boys who had been fifteen years old or more. There was no association between age and the risk of a contralateral slip in girls.

Adolescent↗
PubMed1995

Role of YopH in the suppression of tyrosine phosphorylation and respiratory burst activity in murine macrophages infected with Yersinia enterocolitica.

Tyrosine phosphorylation is an important component of the signaling pathways responsible for the activation of the macrophage respiratory burst. Because the virulence plasmid of Yersinia enterocolitica encodes a phosphotyrosine phosphatase, YopH, it is possible that the pathogenic strategy of Y. enterocolitica involves the disruption of tyrosine phosphorylation in the macrophage leading to inhibition of respiratory burst activity. We have investigated the effects of Yersinia infection on tyrosine phosphorylation and respiratory burst activity in murine bone marrow-derived macrophages. Infection of macrophages with virulent [Ye(pYV+)] but not avirulent [Ye(pYV-)] strains of Y. enterocolitica was found to suppress both tyrosine phosphorylation and respiratory burst activity in response to zymosan. Mutational inactivation of YopH reversed the suppressive effect of Ye(pYV+) on zymosan-induced tyrosine phosphorylation, indicating that YopH is responsible for the dephosphorylation of macrophage phosphotyrosine-containing proteins observed in macrophages infected with the virulent strain of Y. enterocolitica. In contrast, mutational loss of YopH failed to reverse the inhibitory effect of Ye(pYV+) on the zymosan-triggered respiratory burst. We conclude that the inhibition of the macrophage respiratory burst by Y. enterocolitica involves a plasmid-encoded virulence protein(s) other than, or in addition to, YopH.

Animals↗
PubMed1995

Histomorphometric and biochemical characterization of bone following acute severe burns in children.

Severe burns in adults is associated with an uncoupling of normal remodeling, low bone formation without reduced resorption. The risk of osteopenia that may occur under such circumstances is heightened by our detection in a cross-sectional study of low bone mass in severely burned children. We report here the acute histomorphometric and biochemical response of bone to severe burn injury, as well as bone mass in severely burned children. We enrolled 24 patients ages 5.8 to 17.5 years following burns of 63 +/- 16% (SD) body surface area. Serum and urine were collected weekly until iliac crest bone biopsy was obtained 26 +/- 10 days postburn. Seventeen of 18 patients, including 5 patients receiving growth hormone treatment to accelerate wound healing, failed to take up doxycycline in trabecular bone, and had no detectable osteoblasts at the osteoid seam, while eroded surface was normal and osteoblasts were documented by staining. Thus, bone formation was virtually absent. There was an eightfold elevation in urinary free cortisol excretion and high serum levels of acute phase reactants and interleukin-1 beta and -6. Biochemical markers of bone formation, osteocalcin, and type I procollagen propeptide were low, as were resorptive markers urinary pyridinoline and deoxypyridinoline. However, there was no correlation with resorptive surface. Mean age-related z-score for bone mass was -1.06 +/- 1.05, 40 days postburn. Immobilization and endogenous corticosteroid production may be the main factors responsible for acutely reduced bone formation while inflammatory cytokines may mediate resorption.

Absorptiometry, Photon↗
PubMed1995

Silage or limit-fed grain growing diets for steers: I. Growth and carcass quality.

The influence of energy source (silage- [S] or grain- [G] based) on organ growth, carcass quality, and meat acceptability independent of rate of gain was examined. Sixty-four Angus steers were allotted to one of the two treatments and given ad libitum access to silage or limit-fed grain for 145 d. All steers were then given ad libitum access to a grain diet for 45, 75, or 105 d. Eight steers from each treatment were slaughtered at the end of the growing phase and at each of the termination dates. The silage-based growing diet consisted (DM basis) of 55% sorghum silage (averaged 23.6% dry matter), 22% alfalfa hay, 10.8% ground shelled corn, and 10.8% soybean meal and contained 12.8% CP. Dry matter in the grain-based diet, composed of 76.5% ground shelled corn, 5% soybean meal, 13.6% cottonseed hulls, 3.5% molasses, and .4% salt and 1% limestone, contained 12.1% CP. It was limit-fed to produce rates of gain similar to the silage diet eaten ad libitum, using net energy for gain of each diet calculated from organic matter digestibility determined in digestion trials. The finishing diet was similar to the grain growing diet except that alfalfa hay replaced the cottonseed hulls. No implants or ionophores were used. High silage moisture decreased ADG the first 45 d, so steers fed grain gained faster, but thereafter gains were similar. At the end of the growing phase, steers fed grain had heavier shrunk and empty body weights and larger livers. However, liver size was not different when adjusted for growing ADG. By 45 d with ad libitum access to the finishing diet, 75% of the carcasses from steers fed both diets graded Choice. Steers fed silage had tougher (P < .05) steaks with less flavor intensity (P < .05) at the end of the growing phase; these differences diminished after 75 d on feed. These results suggest that choice beef can be produced in only 45 d in the feedlot, but tenderness and flavor among Choice carcasses remained inferior for steers fed silage for at least 75 d on a high-grain diet.

Animals↗