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Biomedical subjects

V Wilson

Publications and source records attributed to V Wilson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of delivery temperature on endocrine stimulation of thermoregulation in lambs born by cesarean section.

We examined the hypothesis that exogenous stimulation with physiological doses of 3,5,3'-triiodothyronine (T(3)) and/or norepinephrine at birth can improve thermoregulation in near-term lambs delivered by cesarean section. This was achieved by investigating the effect of delivery temperature [i.e., warm (30( degrees )C) vs. cool (15( degrees )C) ambient temperatures] on hormonal stimulation on uncoupling protein-1 (UCP1) abundance in brown adipose tissue. In vivo measurements of temperature control (i. e., colonic temperature, oxygen consumption, and incidence of shivering) were made over the first 2.5 h after birth. Each lamb was injected with saline with or without T(3), norepinephrine, or T(3) plus norepinephrine. Irrespective of delivery temperature, abundance of UCP1 increased and incidence of shivering decreased by all hormonal treatments, but this only reduced the rate of decline in colonic temperature of cool-delivered lambs. Oxygen consumption was higher in cool-delivered lambs that were able to fully restore body temperature, an adaptation not observed in controls or any warm-delivered groups. Exogenous administration of endocrine stimulatory factors can enhance the abundance of UCP1 in cesarean-section-delivered lambs with the magnitude of thermoregulatory response being greater at cool than warm delivery temperatures.

Adipose Tissue↗
PubMed2000

Effect of maternal nutrition on brown adipose tissue and its prolactin receptor status in the fetal lamb.

We investigated the influence of maternal nutritional enhancement during the second half of gestation on prolactin receptor (PRLR) abundance in fetal brown adipose tissue (BAT) and liver close to term (i.e. 141-144 d gestation). Ewes were provided with 100% (i.e. control; n = 8) or 150% (i.e. well-fed; n = 7) of their metabolic requirements from 80 to 144 d gestation. Crude plasma membranes were prepared from fetal BAT and hepatic tissue, and individual molecular weight isoforms for the long and short forms of the PRLR were detected by immunoblotting. Mitochondrial preparations were prepared from BAT to measure the amount of the BAT-specific mitochondrial uncoupling protein-1 and its thermogenic activity (i.e. guanosine 5'-diphosphate binding). Fetuses sampled from well-fed ewes were heavier (controls, 3927 +/- 196 g; well-fed, 4783 +/- 219 g; p = 0.01) but possessed less BAT per kilogram body weight (controls, 5.92 +/- 0.43 g/kg; well-fed, 3.85 +/- 0.19 g/kg; p = 0.001), which had a greater uncoupling protein-1 abundance (controls, 56 +/- 5% of reference; well-fed, 78 +/- 9% of reference; p < 0.01) and higher thermogenic activity (controls, 157 +/- 41 pmol guanosine 5'-diphosphate per milligram mitochondrial protein; well-fed, 352 +/- 36 pmol guanosine 5'-diphosphate per milligram mitochondrial protein; p < 0.01) than controls. Multiple isoforms of the long and short forms of the P1LR were detected in all tissues. BAT from well-fed fetuses had a higher abundance of the 15-kD isoform of the long form of the PRLR (controls, 1.6 +/- 0.4 densitometric units; well-fed, 16.3 +/- 2.0 densitometric units; p < 0.001). This isoform was not detected in hepatic tissue. Maternal nutrient intake had no effect on any other isoforms of the PRLR in BAT or liver. In conclusion, increasing the quantity of feed provided in late gestation acts to promote fetal weight and BAT maturation, the combination of which will enhance neonatal viability.

Adipose Tissue, Brown↗
PubMed2000

Guidelines for use of the MS26 daily rate syringe driver in the community.

Many patients cared for in the community have complex care and treatment needs and syringe drivers are commonly used to administer a range of drugs to patients at home. However, serious problems have been associated with this route of administration. In Scotland between 1989 and 1994 there were 23 incidents including 4 fatalities associated with the use of small volume syringe pumps reported to the Common Services Agency supplies division (Scottish Office Home and Health Department (SOHHD), 1995). The four fatalities were attributed to over-infusion (SOHHD, 1995). In those fatal inadvertent incidents no fault was found with the infusion device, suggesting that an inadvertent error had been made by attendants in setting up or in using the device, or that some form of tampering had taken place. The Department of Health issued a hazard warning in 1994 (DoH, 1994) about confusion between the two Sims Graseby syringe drivers the MS16A and the MS26. This article outlines guidance on the use of the Sims Graseby MS26 in the community. Community nurses have a vital role to play in management of syringe drivers, and it is through increased awareness of correct procedures that incidents and fatalities will be avoided.

Analgesics↗
PubMed1999

The Consumer Assessment of Health Plan Study (CAHPS) survey of children's health care.

BACKGROUND: Little is known about the experience of children and families with pediatric care. Asking parents about their experiences and the treatment of their children in health care plans can yield important information about selected aspects of medical care quality. Such data can be used to motivate, focus, and evaluate quality improvement efforts. METHODS: Development of the Child Core Survey followed the survey development principles of the Consumer Assessment of Health Plan Study (CAHPS) project, starting with assembly of existing instruments, consultation with experts, focus groups, and cognitive testing. A field test of the survey was conducted by mail among members enrolled in 1 of 25 plans originally identified as providing health care services to the public employees of the state of Washington (response rate, 52%). RESULTS: The 3,083 respondents rated personal doctors most highly, with overall care and specialty care rated nearly as well, and plan administration rated lowest. Parent-clinician and child-clinician communication, as well as spending sufficient time with the child were the strongest correlates of assessments of overall care and of personal doctors. Plans differed significantly in their performance along all the dimensions of child health care assessed in the survey except for aspects of access ("getting the care you need"). IMPLICATIONS: The Child Core Survey from the CAHPS provides a readily accessible method to assess the interpersonal care of children. Such data could be used to make plans accountable to the needs of children, to focus specific improvement initiatives, or both.

Adolescent↗
PubMed1997

Expression of T protein in the primitive streak is necessary and sufficient for posterior mesoderm movement and somite differentiation.

A characteristic abnormality of chimeras composed of wildtype and T/T (Brachyury) mutant embryonic stem cells is the aggregation and accumulation of mutant cells in the primitive streak and its descendant, the tail bud (V. Wilson, L. Manson, W. C. Skarnes, and R. S. P. Beddington (1995). Development 121, 877-886). To demonstrate that this aberrant behaviour of mutant cells in the streak is due only to the absence of wild-type T protein and to investigate dosage effects of T function on cell deployment during gastrulation, a vector expressing T under the control of its own promoter (which results in T expression in the primitive streak but not in the notochord) was introduced into T/T mutant ES cells carrying a ubiquitous lacZ lineage marker. Four clones (TR clones) that express T appropriately in the streak and rescue abnormal chimeric morphology were recovered. In chimeras, these four clones fall into two distinct categories with respect to their ability to exit from the primitive streak and their subsequent tissue colonisation profile. TR1 and TR4 descendants no longer accumulated in the tail bud and gave rise to all types of mesoderm as well as colonising ventral neurectoderm. Interestingly, TR2 and TR5 cells (which express higher levels of T protein than TR1 and TR4 in vitro) tended to exit the streak prematurely, showed a marked reduction in posterior mesoderm colonisation, and were virtually excluded from ventral neurectoderm. However, while descendants of all four TR clones can colonise dermomyotome at all axial levels, the parent T/T mutant cells only contribute to this tissue rostral to the forelimb bud and are completely excluded from more caudal dermomyotome. These results show that the abnormal aggregation of mutant cells homozygous for the Brachyury deletion (approximately 200 kb) can be ascribed solely to the lack of wild-type T protein, as can the failure of T/T cells to colonise caudal dermomyotome. They also suggest that patterns of cell recruitment from the streak can be influenced by the level of T expression.

Animals↗
PubMed1997

T promoter activity in the absence of functional T protein during axis formation and elongation in the mouse.

The T (Brachyury) gene, which encodes a transcription factor, is involved in the formation of posterior mesoderm. Although studies in Xenopus have shown that T gene expression is responsive to mesoderm inducing factors and furthermore suggest the existence of an autoregulatory loop involving T itself, eFGF, and the FGF receptor, little is known about the regulation of T expression in the mouse. We report here that in the mouse the expression of fgf-4, the putative homologue of Xenopus efgf, is not dependent on the presence of T protein during the first 48 hr of gastrulation. Furthermore, we address the question of autoregulation using a chimeric approach. Introduction of a T promoter-lacZ construct into T/T ES cells results in T promoter activity in the primitive streak and tail bud in the absence of functional T protein. Therefore, we suggest that a direct FGF and T autoregulatory loop is unlikely to operate during gastrulation and axis elongation in the mouse.

Animals↗
PubMed1997

A DNA polymerase alpha accessory protein exhibits structural and functional similarities to SV40 large tumor antigen.

Untransformed cells have been proposed to require a protein homologous to SV40 large tumor antigen (TAg) which functions as a component of the replicase complex during the initiation of DNA synthesis. By definition, this should be a phosphoprotein which interacts with the retinoblastoma protein (pRb) in G0 or early G1, and is capable of binding to and potentiating the activity of DNA polymerase alpha (pol alpha). This protein should also be an ATP-dependent helicase which interacts with the single-stranded DNA (ssDNA) binding protein, RP-A. Because of these requirements, a TAg homologous protein could be expected to contain epitopes with amino acid sequences similar to those of TAg at critical functional sites, such as ATP, pRb and pol alpha binding sites. TAg and a putative cellular homolog of TAg, DNA pol alpha accessory protein (alpha AP), were compared for pRb and pol alpha interaction, and for immunological identity. The analyses utilized immunoaffinity-purified TAg and pRb from a baculovirus expression system, and DNA pol alpha/primase and alpha AP chromatographically isolated from a mouse lymphocytic leukemia cell line. Monoclonal antibodies specific for the pol alpha or pRb binding sites on TAg interacted with alpha AP strongly enough to be employed for immunoaffinity purification of alpha AP. Anti-pRb and anti-TAg reciprocally coimmunoprecipitated pRb bound to TAg and pRb bound to alpha AP. The functional consequences of pol alpha interaction with TAg or alpha AP in the presence or absence of pRb was determined using pol alpha nucleotide incorporation assays. alpha AP exhibited the capacity to stimulate pol alpha activity, a capacity which was diminished in the presence of pRb. Lastly, TAg and alpha AP independently co-purified with pol alpha through a multi-step chromatographic protocol. These data indicate that a pol alpha accessory protein, alpha AP, exhibits functional and immunological similarities to SV40 TAg, suggest that alpha AP is involved in regulation of the initiation of DNA synthesis, and support the proposal that alpha AP may be a normal cell protein homologous to SV40 large T antigen.

Animals↗
PubMed1997

Misexpression of Cwnt8C in the mouse induces an ectopic embryonic axis and causes a truncation of the anterior neuroectoderm.

Transgenic embryos expressing Cwnt8C under the control of the human beta-actin promoter exhibit duplicated axes or a severely dorsalised phenotype. Although the transgene was introduced into fertilised eggs all duplications occurred within a single amnion and, therefore, arose from the production of more than one primitive streak at the time of gastrulation. Morphological examination and the expression of diagnostic markers in transgenic embryos suggested that ectopic Cwnt8C expression produced only incomplete axis duplication: axes were always fused anteriorly, there was a reduction in tissue rostral to the anterior limit of the notochord, and no duplicated expression domain of the forebrain marker Hesx1 was observed. Anterior truncations were evident in dorsalised transgenic embryos containing a single axis. These results are discussed in the light of the effects of ectopic Xwnt8 in Xenopus embryos, where its early expression leads to complete axis duplication but expression after the mid-blastula transition causes anterior truncation. It is proposed that while ectopic Cwnt8C in the mouse embryo can duplicate the primitive streak and node this only produces incomplete axis duplication because specification of the anterior aspect of the axis, as opposed to maintenance of anterior character, is established by interaction with anterior primitive endoderm rather than primitive streak derivatives.

Actins↗
PubMed1997

Increasing rehab utilization. A CQI approach.

As managed care stresses the bottom line, home care providers feel the pressure to achieve the best, most cost-effective outcomes possible. One provider in Colorado found a way to educate its staff on when it is appropriate to refer patients to rehabilitation specialists so they can recover more quickly and effectively.

Colorado↗
PubMed1997

High frequency of K-ras codon 12 mutations in bronchoalveolar lavage fluid of patients at high risk for second primary lung cancer.

A high frequency of K-ras mutations may indicate preneoplastic changes in the bronchial epithelium as a result of genotoxic injury. With the use of sensitive detection techniques, we report a higher prevalence of K-ras mutations in bronchoalveolar lavage than has been reported previously for lung cancer. A PCR/ligase chain reaction technique was used to determine K-ras codon 12 mutations in a group of 52 bronchoalveolar lavage specimens from patients at risk of a second lung cancer. Of the specimens examined, 84% contained at least one mutation in K-ras codon 12, corroborated by an allele-specific hybridization method. These results suggest that point mutations in K-ras codon 12 are widespread in the bronchial epithelium. Based on these preliminary findings, further evaluation of this efficient sensitive assay to monitor K-ras status should be conducted in larger clinical cohorts where clinical outcomes will ultimately be available. Such a trial will define the utility of K-ras codon 12 mutation status as a marker of lung cancer.

Bronchoalveolar Lavage Fluid↗
PubMed1996

Cardiovascular risk factors in British children from towns with widely differing adult cardiovascular mortality.

OBJECTIVE: To examine whether cardiovascular risk factors differ in children from towns in England and Wales with widely differing adult cardiovascular death rates. DESIGN: School based survey conducted during 1994 in 10 towns, five with exceptionally high adult cardiovascular mortality (standardised mortality ratio 131-143) and five with exceptionally low adult cardiovascular mortality (64-75). Towns were surveyed in high-low pairs. SUBJECTS: 3415 white children aged 8-11 years with physical measurements (response rate 75%), including 1287 with blood samples (response rate 64%), of whom 515 had blood samples taken 30 minutes after a glucose load. RESULTS: Children in towns with high cardiovascular mortality were on average shorter than those in towns with low mortality (mean difference 1.2 cm; 95% confidence interval 0.3 to 2.1 cm; P = 0.02) and had a higher ponderal index (0.34 kg/m3; 0.16 to 0.52 kg/m3; P = 0.006). Mean systolic pressure was higher in high mortality towns, particularly after adjustment for height (2.0 mm Hg; 0.8 to 3.2 mm Hg; P = 0.009). Mean waist:hip ratio, total cholesterol concentration, and 30 minute post-load glucose measurements were similar in high and low mortality towns. The differences in height and blood pressure between high and low mortality towns were unaffected by standardisation for birth weight. CONCLUSIONS: The differences in height, ponderal index, and blood pressure between towns with high and low cardiovascular mortality, if persistent, may have important future public health implications. Their independence of birth weight suggests that the childhood environment rather than the intrauterine environment is involved in their development.

Adult↗
PubMed1996

Cell fate and morphogenetic movement in the late mouse primitive streak.

A prospective fate map of the late gastrulation mouse primitive streak has been charted in 8.5 dpc mouse embryos developed in culture, using the lineage marker DiI to label groups of cells. As at earlier stages, the fate of cells in the 8.5 dpc primitive streak is regionalised such that successively more caudal regions of the streak give rise to more lateral mesoderm. While most labelled cells over a 24 or 48 h culture period exit from the primitive streak, some are consistently found to remain within it. The most conspicuous resident population is present in the node. To determine when ingression of ectoderm through the streak ceases, ectoderm cells of the streak and posterior neuropore of 8.5-10.0 dpc embryos were labelled. Involution of surface cells to form mesoderm continues until closure of the posterior neuropore but is not seen thereafter.

Affinity Labels↗
PubMed1996

An accessory protein enhances both DNA binding and activity of DNA polymerase alpha isolated from normal, but not transformed, human fibroblasts.

DNA polymerase alpha/primase (pol alpha) isolated from fibroblasts established from a 66-year-old human donor (GM3529) exhibited decreased specific activity compared with pol alpha from either fetal-derived fibroblasts (WI38), or pSV3.neo-transformed GM3529 fibroblasts. The pol alpha specific activity decrease was correlated with a decreased proliferative capacity frequently seen in cells from aged donors. Pol alpha isolated from pSV3.neo-transformed GM3529 cells (GM3529T) exhibited a single isoform with about 10-fold higher specific activity than pol alpha from GM3529 cells. GM3529T pol alpha was immunoreactive with both anti-pol alpha and anti-SV40 large tumor antigen. Polymerases from GM3529 and GM3529T cells were treated with a pol alpha accessory protein, alpha AP, isolated from L1210 cells. Pol alpha from GM3529T cells showed no increase in activity in the presence of alpha AP, while pol alpha isolated from GM3529 cells exhibited about an 8-fold increase in activity after treatment with alpha AP. Double stranded SV40 DNA containing multiple ori sequences exhibited a greater decrease in electrophoretic mobility in the presence of GM3529T pol alpha than when treated with GM3529 pol alpha. In the presence of pol alpha from either GM35229 or GM3529T cells SV40 dsDNA exhibited a decrease in electrophoretic mobility, and in each instance addition of alpha AP resulted in an even greater decrease in DNA mobility. These data indicate that alpha AP increased pol alpha binding to SV40 dsDNA, or that alpha AP bound the DNA in addition to previously bound pol alpha. GM3529 pol alpha also bound non-specific, non-SV40, dsDNA, whereas GM3529T pol alpha with associated TAg did not bind the non-viral dsDNA unless alpha AP was added to the preparation. While not all human diploid fibroblast cell lines derived from aged human donors necessarily exhibit decreased proliferative capacity compared with cells from young donors, decreased specific activity associated with a decline in cellular DNA synthesis is typical of pol alpha from cells derived from aged human donors. We suggest that a decrease in endogenous alpha AP interaction with pol alpha may account, in part, for the loss of DNA binding affinity and specific activity of pol alpha from GM3529 cells derived from an aged donor.

Aged↗
PubMed1996

Chromosomal evolution in duiker antelope (Cephalophinae: Bovidae): karyotype comparisons, fluorescence in situ hybridization, and rampant X chromosome variation.

Fluorescence in situ hybridization (FISH) and conventional banding techniques were used to identify patterns of similarity among the genomes of six species of antelope, subfamily Cephalophinae. The G-banded euchromatic portions of the autosomes were invariable in all species; however, significant modifications of the X chromosomes were detected. Two of the taxa, Cephalophus maxwellii and C. monticola, were characterized by acrocentric X's, while X chromosome morphology varied from submetacentric to metacentric in the remaining species (C. dorsalis, C. natalensis, Sylvicapra grimmia, and C. silvicultor). The short arm of the X was heterochromatic in each species. Total genomic DNAs from these antelope were used as hybridization probes against Cephalophus metaphase chromosomes and resulted in robust fluorescence in the pericentromeric region of each autosome and in the heterochromatic short arm of the X chromosome, indicating complimentarity of DNA sequences in these regions. Conversely, chromosome painting involving genomic DNAs derived from the subfamilies Alcelaphinae (Pygargus dorcas) and Neotraginae (Oreotragus oreotragus) showed a marked absence of hybridization at these sites. Additionally, X chromosome comparisons between the Cephalophinae and Bovinae (represented by Bos taurus) revealed two euchromatic pericentric inversions which had occurred since their common ancestry. There is good G-band homoeology between the inverted cattle chromosome region Xq12 --> q34 and most of the proximal portion of Xq in duikers, as well as between the distal third of the duiker Xq and the cattle Xp. The latter rearrangement was further confirmed by in situ hybridization using a probe containing an insert spanning bands p12 to p14 of the cattle X chromosome.

Animals↗