Biomedical subjects

W A Phillips

Publications and source records attributed to W A Phillips.

At least 19 recordsLinked to original sources

PubMed2006

ST7-mediated suppression of tumorigenicity of prostate cancer cells is characterized by remodeling of the extracellular matrix.

Multiple lines of evidence have provided compelling evidence for the existence of a tumor suppressor gene (TSG) on chromosome 7q31.1. ST7 may be the target of this genetic instability but its designation as a TSG is controversial. In this study, we show that, functionally, ST7 behaves as a tumor suppressor in human cancer. ST7 suppressed growth of PC-3 prostate cancer cells inoculated subcutaneously into severe combined immunodeficient mice, and increased the latency of tumor detection from 13 days in control tumors to 23 days. Re-expression of ST7 was also associated with suppression of colony formation under anchorage-independent conditions in MDA-MB-231 breast cancer cells and ST7 mRNA expression was downregulated in 44% of primary breast cancers. Expression profiling of PC-3 cells revealed that ST7 predominantly induces changes in genes involved in re-modeling the extracellular matrix such as SPARC, IGFBP5 and several matrix metalloproteinases. These data indicate that ST7 may mediate tumor suppression through modification of the tumor microenvironment.

Base Sequence↗

PubMed2004

Pop-out from abrupt visual onsets.

We report a novel psychophysical paradigm that distinguishes the information present in abrupt stimulus onset from that in the following display. The task is to pick the one odd item from a set added to a pre-existing background of similar items. When all new items are added simultaneously, observers are impaired even at distinguishing one red item amongst several green ones. An asynchrony of about 40 ms between target and distracter items restores performance, with evidence that it is cortical, rather than stimulus timing difference that is significant. The results are consistent with a role for neural synchrony in dynamic grouping.

Color Perception↗

PubMed2004

Effect of live weight gain of steers during winter grazing: I. Feedlot performance, carcass characteristics, and body composition of beef steers.

Two experiments were conducted to examine the effect of previous BW gain during winter grazing on subsequent growth, carcass characteristics, and change in body composition during the feedlot finishing phase. In each experiment, 48 fall-weaned Angus x Angus-Hereford steer calves were assigned randomly to one of three treatments: 1) high rate of BW gain grazing winter wheat (HGW), 2) low rate of BW gain grazing winter wheat (LGW), or 3) grazing dormant tallgrass native range (NR) supplemented with 0.91 kg/d of cottonseed meal. Winter grazing ADG (kg/d) for HGW, LGW, and NR steers were, respectively, 1.31, 0.54, 0.16 (Exp. 1) and 1.10, 0.68, 0.15 (Exp. 2). At the end of winter grazing, four steers were selected randomly from each treatment to measure initial carcass characteristics and chemical composition of carcass, offal, and empty body. All remaining steers were fed a high-concentrate diet to a common backfat end point. Six steers were selected randomly from each treatment for final chemical composition, and carcass characteristics were measured on all steers. Initial fat mass and proportion in carcass, offal, and empty body were greatest (P < 0.001) for HGW, intermediate for LGW, and least for NR steers in both experiments. Live BW ADG and gain efficiency during the finishing phase did not differ (P = 0.24) among treatments, but DMI (% of mean BW) for NR and LGW was greater (P < 0.003) than for HGW steers. Final empty-body composition did not differ (P = 0.25) among treatments in Exp. 1. In Exp. 2, final carcass and empty-body fat proportion (g/kg) was greater (P < 0.03) for LGW and NR than for HGW steers. Accretion of carcass fat-free organic matter was greater (P < 0.004) for LGW than for HGW and NR steers in Exp. 1, but did not differ (P = 0.22) among treatments in Exp. 2. Fat accretion in carcass, offal, and empty body did not differ (P = 0.19) among treatments in Exp. 1, but was greater (P < 0.05) for LGW and NR than for HGW steers in Exp. 2. Heat production by NR steers during finishing was greater (P < 0.02) than by HGW steers in Exp. 1 and 2. Differences in ADG during winter grazing and initial body fat content did not affect rate of live BW gain or gain efficiency during finishing. Feeding steers to a common backfat thickness end point mitigated initial differences in carcass and empty-body fat content. However, maintenance energy requirements during finishing were increased for nutritionally restricted steers that were wintered on dormant native range.

Adipose Tissue↗

PubMed2003

Analysis of the candidate 8p21 tumour suppressor, BNIP3L, in breast and ovarian cancer.

Loss of heterozygosity (LOH) on the short arm of chromosome 8, at 8p12-p23, is one of the most frequent genetic events in both breast and ovarian cancer, suggesting the location of a shared tumour suppressor gene. Microcell-mediated chromosome transfer of chromosome 8 suppresses tumorigenicity and growth of colorectal and prostate cancer cell lines, further supporting the presence of a tumour suppressor gene on 8p. We have taken a candidate gene approach to try to identify this tumour suppressor gene at 8p12-p23. BNIP3L, which has sequence homology to pro-apoptotic proteins and the ability to suppress colony formation in soft agar, is located at 8p21, within a region of ovarian cancer LOH, breast cancer LOH and prostate cancer metastasis suppression. BNIP3L expression was assessed by both RT-PCR and Northern blot analysis in breast and ovarian cancer cell lines and found to be expressed at similar levels relative to expression in their respective normal epithelial cell lines. Genetic analysis of BNIP3L in 40 primary ovarian and 25 primary breast tumours identified one somatic, intronic mutation in one ovarian tumour, as well as several polymorphisms, including one resulting in an amino-acid substitution. These data suggest that BNIP3L is unlikely to be the target of 8p LOH in ovarian or breast cancer.

Apoptosis↗

PubMed2002

Digestibility and dry matter intake of diets containing alfalfa and kenaf.

Two experiments were conducted to determine the dietary value of pellets containing kenaf (Hibiscus cannabinus cv. 'Everglade 41') hay. Averaged across both experiments, kenaf pellets contained 82.6% kenaf hay, 16.6% liquid molasses, and 0.8% mineral oil. The chemical composition of the kenaf pellet was 12.6% crude protein (CP), 41.2% neutral detergent fiber (NDF), and 14.4% acid detergent fiber (ADF). In Exp. 1 (digestion and N balance trial), 18 lambs (body weight [BW] = 36.4 kg) were blocked by BW. Lambs were randomly assigned within a block to Diet 1 (59.5% corn and 40.5% alfalfa pellet), Diet 2 (59.7% corn, 28.4% alfalfa pellets, and 11.9% kenaf pellets), or Diet 3 (59.6% corn, 16.5% alfalfa pellets, and 23.9% kenaf pellets). Diets were formulated so that CP was the first-limiting nutrient. Each diet was limit-fed at 2.4% of BW. Replacing alfalfa pellets with kenaf pellets tended to decrease (P = 0.10) CP and ADF intakes, but increased (P = 0.01) DM digestibility. Diet had no effect (P = 0.33) on N balance. In Exp. 2 (dry matter [DM] intake trial), 32 lambs (BW = 30.4 kg) were blocked by gender and BW. Within a block, lambs were randomly assigned to one of four diets in a 2 x 2 factorial arrangement. Main effects were hay (bermudagrass or fescue) and supplemental protein source (kenaf or alfalfa pellets). Lambs were housed in individual pens with ad libitum access to the assigned hay. Supplemental protein was fed (185 g of DM) once daily. Hay intake was measured weekly for 8 wk. Lambs consumed more (P = 0.002) fescue than bermudagrass hay (743 vs 621 g/ d). Lambs fed fescue hay gained weight more rapidly (P = 0.001) than lambs fed bermudagrass hay (120 vs 72 g/d). Hay intake and ADG were similar (P = 0.90) for lambs fed alfalfa or kenaf pellets. Kenaf hay mixed with molasses and mineral oil can be formed into a pellet. In the diets used in this experiments, kenaf pellets can replace alfalfa pellets in diets fed to lambs without altering forage intake, gain, or N retention.

Animal Feed↗

PubMed2001

The phosphatidylinositol 3'-kinase p85alpha gene is an oncogene in human ovarian and colon tumors.

Phosphatidylinositol 3'-kinases (PI3ks) are a family of lipid kinases that play a crucial role in a wide range of important cellular processes associated with malignant behavior including cell growth, migration, and survival. We have used single-strand conformational polymorphism/heteroduplex analysis to demonstrate the presence of somatic mutations in the gene for the p85alpha regulatory subunit of PI3k (PIK3R1) in primary human colon and ovarian tumors and cancer cell lines. All of the mutations lead to deletions in the inter-SH2 region of the molecule proximal to the serine608 autoregulatory site. Expression of a mutant protein with a 23 amino acid deletion leads to constitutive activation of PI3k providing the first direct evidence that p85alpha is a new oncogene involved in human tumorigenesis.

Aged↗

PubMed2001

Id2 is a target of the beta-catenin/T cell factor pathway in colon carcinoma.

Activation of beta-catenin/T cell factor (TCF) transcription as a result of mutations in the adenomatous polyposis coli (APC) and/or beta-catenin genes occurs in the majority of colon tumors. An increasing number of genes, including c-myc and cyclin D1, have been implicated as targets of this pathway. We now report that the dominant negative helix-loop-helix regulator Id2 is also a target of the beta-catenin/TCF transcription pathway in colon adenocarcinoma. Investigation of the mechanism for the overexpression of Id2 in colon carcinoma cells demonstrated that the Id2 promoter is activated, and the Id2 protein is up-regulated by beta-catenin. Conversely, reducing free beta-catenin blocked this induction of promoter activity. We have also used an electrophoretic mobility shift assay and supershift to identify a motif in the Id2 promoter that binds to TCF4 protein. Site-directed mutagenesis of this motif abolished promoter reporter activity. Both transfection of Id2 into SW480 cells and induction of Id2 in HT29 colon cells was found to increase anchorage-independent survival of these cells. Growing evidence associates disruption to Id2 expression with tumorigenesis, and our findings suggest that this dysregulation of Id2 expression is due to the activation of the beta-catenin/TCF pathway.

Adenocarcinoma↗

PubMed2001

Functional abnormalities in protein tyrosine phosphatase epsilon-deficient macrophages.

Protein tyrosine phosphatase epsilon (PTP epsilon)-deficient mice were generated by targeted deletion of exons 3, 4, and 5 of the Ptpre gene. Mice homozygous for this deletion (Ptpre(Delta3-5)) were fertile, bred and developed normally and exhibited no overt phenotype. However, closer examination of the function of macrophages from these mice revealed a defect in the regulation of the respiratory burst. While bacterial lipopolysaccharide (LPS) or tumour necrosis factor alpha (TNFalpha) were able to prime bone marrow-derived macrophages (BMM) from wild type (Ptpre(+)) macrophages for an enhanced respiratory burst, they were unable to do so in macrophages from PTP epsilon-deficient mice. PTP epsilon-deficient BMM also had abnormalities in cytokine production with a reduced ability to produce TNFalpha and enhanced IL-10 production in response to challenge with LPS. These findings suggest an important role for PTP epsilon in the control of macrophage function.

Animals↗

PubMed2001

Expression of Wnt genes in human colon cancers.

A polymerase chain reaction-based approach was used to study the expression of Wnt genes in human colon carcinoma tissue and normal colon mucosa. In a number of cases Wnts 2, 4, 5a, 6 and/or 7a were found to be more highly expressed in colon carcinoma tissue compared to surrounding normal-appearing mucosa from the same patients. Wnts 4, 5a, 6 and 7a, but not 2, were also found to be expressed in colon cancer cell lines. The increased levels of expression of these Wnt genes in tumor tissue may indicate their possible involvement in human colon tumorigenesis.

Cell Line↗

PubMed2001

Expression of interleukin-6, leukemia inhibitory factor and their receptors by colonic epithelium and pericryptal fibroblasts.

BACKGROUND AND AIM: The cellular configuration of the human colon suggests a predetermined organization that creates specific microenvironments. The role of pericryptal fibroblasts in this microenvironment has been the subject of considerable speculation. This study examined the expression of growth factors and their receptors by colonic crypt epithelium and pericryptal fibroblasts. METHODS AND RESULTS: Pericryptal fibroblast cells were isolated and cultured from decrypted human colonic mucosa. The pericryptal fibroblast cells expressed messenger RNA (mRNA) for interleukin-6 (IL-6), leukemia inhibitory factor (LIF), LIF receptor alpha, and the common coreceptor glycoprotein 130 (GP130), but not the IL-6 receptor alpha. Interleukin-6 protein expression was confirmed by the analysis of conditioned medium and immunohistochemistry. In comparison, normal colonic epithelial cells express mRNA for LIF but not IL-6 as well as the receptors for GP-130, IL-6 receptor alpha but not LIF receptor alpha. As cultures of normal human colonic epithelial cells were not available, the conditioned medium was assayed from established colon carcinoma cell lines and demonstrated a secretion of LIF but not IL-6 protein. CONCLUSION: The expression of reciprocal cytokine and receptor expression suggest that there is a paracrine relationship between pericryptal fibroblasts and colonic epithelium.

Antigens, CD↗

PubMed2001

Genetic x environment interactions on blood constituents of Angus, Brahman, and reciprocal-cross cows and calves grazing common bermudagrass or endophyte-infected tall fescue.

Over a 2-yr period, effects of genotype and forage on blood metabolites, enzymes, and minerals were determined in Angus, Brahman, Angus x Brahman (sire x dam), and Brahman x Angus cows, and 129 calves from these cows sired by Hereford bulls. Cows and calves continuously grazed either common bermudagrass or endophyte-infected 'Kentucky-31' tall fescue pastures throughout the year. Blood samples were collected via jugular venipuncture in April, August, October (weaning), and November (after 30 d in a feedlot) of each year. Plasma urea N concentrations of cows and calves were affected by forage (P < 0.01) and breed (P < 0.05). Plasma cholesterol and FFA concentrations of cows were affected by forage (P < 0.01) and breed (P < 0.05). In calves, antibody titers to infectious bovine rhinotracheitis virus were not affected by forage but were affected by breed. Serum inorganic P concentrations of calves and cows were affected by forage (P < 0.05). Serum P concentrations and alkaline phosphatase activity of calves were affected by breed (P < 0.05). Calves grazing bermudagrass had higher (P < 0.05) serum concentrations of Fe and total iron binding capacity (TIBC). There was evidence of maternal heterosis for concentrations of free fatty acids, cholesterol, aspartate aminotransferase, Ca, Mg, alkaline phosphatase, ceruloplasmin, Fe, and TIBC. There was evidence of grandmaternal effects for plasma concentrations of urea N, cholesterol, Ca, P, Mg, and alkaline phosphatase. These results suggest that calves and cows grazing tall fescue are generally on a lower plane of nutrition than those grazing bermudagrass and that Brahman x Angus and Angus x Brahman crossbred cows and their calves seen to be more tolerant of the negative effects of tall fescue than the average of their purebred contemporaries.

Animals↗

PubMed2001

Genotype x environment interactions for postweaning performance in crossbred calves grazing winter wheat pasture or dormant native prairie.

Data from 403 calves from Angus, Brahman, and reciprocal-cross cows sired by Polled Hereford bulls were used to evaluate the impact of postweaning backgrounding forages on postweaning BW, gains, and carcass traits. Calves were born (spring of 1991 through 1994) and reared on either endophyte-infected tall fescue or common bermudagrass pastures. After weaning, calves were transported 360 km to the Grazinglands Research Laboratory, west of El Reno, OK, and, within breed and preweaning forage, were assigned to one of the following winter stocker treatments: 1) winter wheat pasture or 2) dormant native prairie plus supplemental CP. In March, winter stocker treatments were ended and calves were grazed as a single group on cool-season grasses until early July (1992, 1993, and 1994) or late May (1995), when the feedlot phase began. In the feedlot, calves were fed a high concentrate diet for an average of 120 d until a backfat thickness of > 10 mm was reached. Calves were shipped in truck load lots to Amarillo, TX (350 km), for processing and collection of carcass data. Averaged over calf breed group, calves wintered on wheat pasture gained faster (P < 0.01) during the stocker phase (0.71 vs 0.43 kg); had heavier (P < 0.01) final feedlot weights (535 vs 512 kg); lower feedlot (P < 0.01) ADG (1.37 vs 1.53 kg); heavier (P < 0.01) carcass weights (337 vs 315 kg); larger (P < 0.01) longissimus muscle (84.9 vs 81.8 cm2); higher percentage (P < 0.01) of kidney, heart, and pelvic fat (2.32 vs 2.26); and higher (P < 0.01) dressing percentage (62.2 vs 61.3) than calves backgrounded on native prairie. Maternal heterosis for stocker ADG was evident in calves backgrounded on native prairie but not on winter wheat (P < 0.10), but the two environments were similar in maternal heterosis for feedlot ADG and carcass traits. Calves wintered on native prairie were restricted in growth and expressed compensatory gain during the feedlot phase but not during the spring stocker phase. Dormant native grasses can be used to winter stocker calves excess to the winter wheat pasture needs, but ownership of these calves would have to be retained through the feedlot phase to realize any advantage of built-in compensatory gain. Finally, these data suggest that expression of maternal heterosis for weight gain is more likely in calves backgrounded on native prairie than in calves grazed on winter wheat.

Animal Feed↗

PubMed2001

A comparison of native tallgrass prairie and plains bluestem forage systems for cow-calf production in the southern great plains.

The objective of this study was to compare an introduced warm-season perennial grass (plains bluestem, Bothriochloa ischaemum) to native tallgrass prairie for cow-calf production. Three systems were used, two based on tallgrass prairie with two different forms of protein supplementation and one based on plains bluestem as the primary forage. The systems were as follows: 1) native tallgrass prairie with pelleted oilseed meal as the winter protein supplement (native-control); 2) native tallgrass prairie with limited access to wheat pasture as the winter protein supplement (native-wheat); and 3) plains bluestem with limited access to wheat pasture as the protein supplement (bluestem-wheat). Oilseed meal protein supplements were fed twice weekly. Cows grazing wheat pasture were allowed 6 h of grazing twice weekly. Ninety-nine cows per year were used over the 3-yr study. Cows were sired by either Charolais, Gelbvieh, Angus, or Hereford bulls out of commercial Angus-Hereford dams. Calves were sired by Simmental bulls. Calving and weaning rate increased over time but did not differ among systems or breed types. System did not influence the size or body condition score of cows or the performance of calves, but changes in the weight and condition scores of cows were greater on either native system than on the bluestem-wheat system. Cows from Charolais and Gelbvieh bulls were taller (P < 0.05), and heavier (P < 0.05), and weaned heavier (P < 0.05) calves than cows from Angus or Hereford bulls. The weight of cows on the bluestem-wheat system tended to decrease over time, whereas cows grazing on the native systems tended to gain weight over time. The native-control system was the most profitable system based on cow production. If excess hay produced from the bluestem-wheat system was sold as a cash crop, then this system was the most profitable. In general, we conclude that limit-grazing wheat pasture is a viable alternative to oilseed meal as protein supplement for wintering dry cows. Although the bluestem system had 2.5 times the carrying capacity of the native prairie systems, increased productivity was offset by increased production costs. All systems were equal on a cow basis for providing nutrients for the cow-calf production system.

Animal Feed↗

PubMed2000

Methylation of exon 2 of p16 is associated with late stage oesophageal cancer.

Methylation of the p16 gene was studied in 16 oesophageal tumours. Five (31%) of the tumours were found to be methylated in exon 1 and eight (50%) were methylated in exon 2. The loss of p16 protein correlated with methylation of exon 1 (P = 0.005). However, methylation of exon 2, but not exon 1, was found to be associated with late stage tumours (P = 0.01). We conclude that the methylation of exon 2 of p16 may have effects on the progression of oesophageal tumours that are independent of the expression of the p16 protein.

Adenocarcinoma↗

PubMed2000

Short-chain fatty acids reduce expression of specific protein kinase C isoforms in human colonic epithelial cells.

LIM1215 colon cancer cells were used as a model of human colonic epithelium to examine the effects of butyrate on protein kinase C (PKC) activity and isoform expression. On Western blot analysis, LIM1215 cells express the PKC isoforms alpha, beta, epsilon, zeta, and lambda, but not gamma, straight theta, or micro. Treatment with 2 mM butyrate for 48 h reduced cellular PKC activity up to 50% and specifically reduced the expression of PKC alpha and PKC epsilon. Similar results were obtained using Caco-2 colon cancer cells. These effects were neither a consequence of the induction of differentiation itself nor the result of direct or indirect activation of PKC. Although dependent on gene transcription and protein synthesis, the effect was not due to a reduction in the synthesis of PKC protein. Butyrate's effect was independent of its beta-oxidation but was mimicked, at least in part, by trichostatin A, an inhibitor of histone deacetylase.

Butyrates↗

PubMed2000

Sodium butyrate-induced differentiation of human LIM2537 colon cancer cells decreases GSK-3beta activity and increases levels of both membrane-bound and Apc/axin/GSK-3beta complex-associated pools of beta-catenin.

Analysis of the glycogen synthase kinase-3beta (GSK-33) activity in several colon cancer cell lines suggested a correlation between comparatively low enzyme activity and moderate to high differentiation status. Treatment of LIM2537 cells, a poorly differentiated colon cancer cell line, with the potent differentiating agent sodium butyrate resulted in 34% reduction in GSK-3beta activity in the treated cells (P < 0.028, n = 3). Decreases in GSK-3beta activity were paralleled by stabilization of cytoplasmic beta-catenin, a hallmark of Wnt signaling. However, in contrast to Wnt signaling, expression of the beta-catenin/ TCF target genes c-myc and cyclin D1 did not appear to be increased in the sodium butyrate-treated cells. Interestingly, expression of membrane-bound beta-catenin was increased in the sodium butyrate-treated cells. This suggests that, in the context of cellular differentiation, increases in beta-catenin expression may be sequestered at the cell membrane and suggests that a possible role of sodium butyrate in promoting differentiation may be via increasing the levels of beta-catenin available for cell adhesion.

Alkaline Phosphatase↗

PubMed2000

Interactions between coincident and orthogonal cues to texture boundaries.

Arrays with horizontal or vertical texture boundaries formed by element orientation and length cues were displayed, and the texture boundary formed by one cue was specified as the target. The boundaries formed by the two cues were coincident on some trials and orthogonal on others. Observers' accuracy in reporting the orientation of the target boundary was improved by a coincident nontarget boundary and was worsened by an orthogonal one. Conditional mutual information measures are used to show how effects due to contextual modulation can be distinguished from effects due to additive combination of the cues. The results of five experiments are interpreted as evidence that the transmission of information about specific texture boundary cues is modulated by task context but not by a coincident or orthogonal boundary in another cue. We therefore distinguish between the effects of "context," as shown by the effects of any variable not called the target, and "modulatory contextual effects," as shown by the effects of one variable on the transmission of information specifically about another.

Adult↗

PubMed2000

Microsatellite instability in gastrointestinal tract tumours.

Although a number of studies have documented microsatellite instability (MSI) in gastrointestinal tumours, the clinical significance is uncertain. In this study the MSI status and clinicopathological features were examined in gastric and colorectal tumours. Eighty-four gastrointestinal tumours were examined for MSI. Normal and tumour DNA isolated from the same patients were analysed at five different microsatellite loci. Clinical features of these patients were also collated and compared with MSI status. High level MSI (MSI-H) (as defined by instability in 2 or more microsatellites) was detected in 6 out of 47 (13%) colon tumours and 6 of 37 (16%) gastric tumours. The frequency of MSI-H between these groups was not statistically significant (P = 0.36). There was no significant correlation with patient age or gender, UICC stage, or degree of differentiation of the tumour. This was true both when analysed as a group, as well as when divided into colon and gastric sites. Our results confirm that a proportion of sporadic tumours from the colon and stomach exhibit an MSI-H phenotype. However, there was no significant relationship between the presence of MSI and any of the clinicopathological characteristics studied.

Colonic Neoplasms↗