Biomedical subjects

S L White

Publications and source records attributed to S L White.

At least 19 recordsLinked to original sources

PubMed2006

Measurement of the asymmetry in the decay Omega+-->LamdaKappa+-->rhopi+Kappa+.

The asymmetry in the rho angular distribution in the sequential decay Omega+-->LamdaKappa+-->rhopi+Kappa+. has been measured to be alphaOmegaalphaLamda=[+1.16+/-0.18(stat)+/-0.17(syst)]x10(-2) using 1.89x10(6) unpolarized Omega+ decays recorded by the HyperCP (E871) experiment at Fermilab. Using the known value of alphaLamda, and assuming that alphaLamda=-alphaLamda, alphaOmega=[-1.81+/-0.28(stat)+/-0.26(syst)]x10(-2). A comparison between this measurement of alphaOmegaalphaLamda and recent measurements of alphaOmegaalphaLamda made by HyperCP shows no evidence of a violation of CP symmetry.

Journal Article↗

PubMed2006

Trophic factor modulation of cocaine- and amphetamine-regulated transcript peptide expression in explant cultured guinea-pig cardiac neurons.

The present study investigated the influence of trophic factors on the expression of cocaine- and amphetamine-regulated transcript peptide (CARTp) in guinea-pig cardiac ganglia maintained in explant culture. In acutely isolated cardiac ganglia preparations, <1% of the cholinergic cardiac neurons exhibited CARTp immunoreactivity. In contrast, this number increased to >25% of the cardiac neurons after 72 h in explant culture. This increase in the number of CARTp neurons in cultured cardiac ganglia explants was accompanied by an increase in CARTp transcript levels as assessed by real time polymerase chain reaction. Treatment of cardiac ganglia cultures with neurturin or glial-derived trophic factor (both at 10 ng/ml) for 72 h prevented the increase in neurons that exhibited CARTp immunoreactivity. In contrast, treatment with ciliary neurotrophic factor (50 ng/ml) for 72 h produced a small significant increase in the percentage of CARTp-immunoreactive cardiac neurons and treatment with nerve growth factor (100 ng/ml) had no effect. Neurturin treatment also decreased cardiac neuron CARTp levels after 72 h in explant culture. Cardiac neurons exhibited immunoreactivity to the neurturin receptor GFRalpha2 whereas non-neural cells preferentially exhibited immunoreactivity to the glial-derived neurotrophic factor receptor GFRalpha1 and neurturin transcripts were detected in cardiac tissue extracts. We hypothesize that a target-derived inhibitory factor, very likely neurturin, is a critical factor suppressing the expression of CARTp in guinea-pig cardiac neurons. These observations contrast with those reported in sympathetic neurons that suggest up-regulation of trophic factors after axotomy or during explant culture is a key factor contributing to the up-regulation of many neuropeptides.

Analysis of Variance↗

PubMed2005

Search for the lepton-number-violating decay Xi(-)-->pmu(-)mu(-).

A sensitive search for the lepton-number-violating decay Xi(-)-->pmu(-)mu(-) has been performed using a sample of approximately 10(9) Xi(-) hyperons produced in 800 GeV/c p-Cu collisions. We obtain B(Xi(-)-->pmu(-)mu(-))<4.0x10(-8) at 90% confidence, improving on the best previous limit by 4 orders of magnitude.

Journal Article↗

PubMed2005

Search for DeltaS = 2 nonleptonic hyperon decays.

A sensitive search for the rare decays Omega(-)--> Lambdapi(-) and Xi(0)--> ppi(-) has been performed using data from the 1997 run of the HyperCP (Fermilab E871) experiment. Limits on other such processes do not exclude the possibility of observable rates for |DeltaS| = 2 nonleptonic hyperon decays, provided the decays occur through parity-odd operators. We obtain the branching-fraction limits B(Omega(-)-->Lambdapi(-)) < 2.9 x 10(-6) and B(Xi(0)--> ppi(-)) < 8.2 x 10(-6), both at 90% confidence level.

Journal Article↗

PubMed2005

Evidence for the decay sigma+ --> pmu+ mu-.

We report the first evidence for the decay Sigma(+)-->pmu(+)mu(-) from data taken by the HyperCP (E871) experiment at Fermilab. Based on three observed events, the branching ratio is B(Sigma(+)-->pmu(+)mu(-))=[8.6(+6.6)(-5.4)(stat)+/-5.5(syst)]x10(-8). The narrow range of dimuon masses may indicate that the decay proceeds via a neutral intermediate state, Sigma(+)-->pP(0),P0-->mu(+)mu(-) with a P0 mass of 214.3+/-0.5 MeV/c(2) and branching ratio B(Sigma(+)-->pP(0),P0-->mu(+)mu(-))=[3.1(+2.4)(-1.9)(stat)+/-1.5(syst)]x10(-8).

Journal Article↗

PubMed2005

A novel nonsteroidal antifibrotic oligo decoy containing the TGF-beta element found in the COL1A1 gene which regulates murine schistosomiasis liver fibrosis.

Schistosomiasis mansoni disseminated worm eggs in mice and humans induce granulomatous inflammations and cumulative fibrosis causing morbidity and possibly mortality. In this study, intrahepatic and I.V. injections of a double-stranded oligodeoxynucleotide decoy containing the TGF-beta regulatory element found in the distal promoter of the COL1A1 gene into worm-infected mice suppressed TGF-beta1, COL1A1, tissue inhibitor of metalloproteinase-1, and decreased COL3A1 mRNAs to a lesser extent. Sequence comparisons within the mouse genome found homologous sequences within the COL3A1, TGF-beta1, and TIMP-1 5' flanking regions. Cold competition gel mobility shift assays using these homologous sequences with 5' and 3' flanking regions found in the natural COL1A1 gene showed competition. Competitive gel mobility assays in a separate experiment showed no competition using a 5-base mutated or scrambled sequence. Explanted liver granulomas from saline-injected mice incorporated 10.45 +/- 1.7% (3)H-proline into newly synthesized collagen, whereas decoy-treated mice showed no collagen synthesis. Compared with the saline control schistosomiasis mice phosphorothioate double-stranded oligodeoxynucleotide treatment decreased total liver collagen content (i.e. hydroxy-4-proline) by 34%. This novel molecular approach has the potential to be employed as a novel antifibrotic treatment modality.

Animals↗

PubMed2005

Chronic kidney disease in the general population.

End-stage kidney disease (ESKD), defined as the need for dialysis, receipt of a transplant, or death from chronic kidney failure, generally affects fewer than 1% of the population. However ESKD is the end result of chronic kidney disease (CKD), a widely prevalent but often silent condition with elevated risks of cardiovascular morbidity and mortality and a range of metabolic complications. A recently devised classification of CKD has facilitated prevalence estimates that reveal an "iceberg" of CKD in the community, of which dialysis and transplant patients are the tip. Hypertension, smoking, hypercholesterolemia, and obesity, currently among the World Health Organization's (WHO's) top 10 global health risks, are strongly associated with CKD. The factors, together with increasing diabetes prevalence and an aging population, will result in significant global increases in CKD and ESKD patients. Treatments now available effectively reduce the rate of progression of CKD and the extent of comorbid conditions and complications. The challenges are (1) to intervene effectively to reduce the excess burden of cardiovascular morbidity and mortality associated with CKD, (2) to identify those at greatest risk for ESKD and intervene effectively to prevent progression of early CKD, and (3) to ultimately introduce cost-effective primary prevention to reduce the overall burden of CKD. The vast majority of the global CKD burden will be in developing countries, and policy responses must be both practical and sustainable in these settings.

Disease Progression↗

PubMed2004

Search for CP violation in charged-Xi and Lambda hyperon decays.

We have compared the p and p angular distributions in 117 x 10(6) Xi- -->Lambdapi- -->ppi-pi- and 41 x 10(6) Xi+ -->Lambda pi+ -->p pi+pi+ decays using a subset of the data from the HyperCP experiment (E871) at Fermilab. We find no evidence of CP violation, with the direct-CP-violating parameter AXiLambda identical with (alphaXialphaLambda-alpha Xialpha Lambda)/(alphaXialphaLambda+alphaXialphaLambda)=[0.0+/-5.1(stat)+/-4.4(syst)] x 10(-4).

Journal Article↗

PubMed2004

Cellular responses to ErbB-2 overexpression in human mammary luminal epithelial cells: comparison of mRNA and protein expression.

Microarray analysis offers a powerful tool for studying the mechanisms of cellular transformation, although the correlation between mRNA and protein expression is largely unknown. In this study, a microarray analysis was performed to compare transcription in response to overexpression of the ErbB-2 receptor tyrosine kinase in a model mammary luminal epithelial cell system, and in response to the ErbB-specific growth factor heregulin beta1. We sought to validate mRNA changes by monitoring changes at the protein level using a parallel proteomics strategy, and report a surprisingly high correlation between transcription and translation for the subset of genes studied. We further characterised the identified targets and relate differential expression to changes in the biological properties of ErbB-2-overexpressing cells. We found differential regulation of several key cell cycle modulators, including cyclin D2, and downregulation of a large number of interferon-inducible genes, consistent with increased proliferation of the ErbB-2-overexpressing cells. Furthermore, differential expression of genes involved in extracellular matrix modelling and cellular adhesion was linked to altered adhesion of these cells. Finally, we provide evidence for enhanced autocrine activation of MAPK signalling and the AP-1 transcription complex. Together, we have identified changes that are likely to drive proliferation and anchorage-independent growth of ErbB-2- overexpressing cancer cells.

Breast Neoplasms↗

PubMed2003

Swainsonine stimulates bone marrow cell proliferation and differentiation in different strains of inbred mice.

The immunomodulatory alkaloid swainsonine (8alphabeta-indolizidine-1alpha,2alpha,8beta-triol) has potential for overcoming the bone marrow suppressive effects of cancer chemotherapeutic drugs and radiation. The effect of swainsonine on bone marrow cellularity was evaluated in four different strains (C57BL/6; C3H-HEN; Balb/C and DBA-2 mice) of inbred mice subjected to multiple doses of the alkaloid. Swainsonine treatment stimulated bone marrow cell proliferation in all strains of mice. Examination of the peripheral blood did not reveal any increase in total leukocyte count. In vitro assessment of total colony-forming unit (CFU) capacity of bone marrow cells showed a two- to eight-fold increase in swainsonine treated mice of different strains compared to their corresponding controls given sham injections of physiological saline. Swainsonine induced increase in CFU capacity of bone marrow cells should find clinical application in cancer treatment with chemotherapeutic agents and radiation.

Animals↗

PubMed2002

Milk production and economic measures in confinement or pasture systems using seasonally calved Holstein and Jersey cows.

This 4-yr study examined total lactation performance of dairy cows in two feeding systems: pasture-based and confinement. Spring and fall calving herds were used and each seasonal herd had 36 cows on pasture and 36 cows in confinement with 282 Holstein and 222 Jersey cows included over seven seasonal replicates. Pasture-fed cows received variable amounts of grain and baled haylage depending upon pasture availability. Confinement cows received a total mixed ration with corn silage as the primary forage. Data were collected on milk production, feed costs, and other costs. Pasture-fed cows produced 11.1% less milk than confinement cows. Across treatments, Jerseys produced 23.3% less milk than Holsteins, but calving season and various interactions were not significant. Feed costs averaged $0.95/cow per day lower for pastured cows than confinement cows. Feed costs were lower for Jerseys than Holsteins and for cows calving in spring. Income over feed costs averaged $7.05 +/- 0.34 for confinement Holsteins, $6.89 +/- 0.34 for pastured Holsteins, $5.68 +/- 0.34 for confinement Jerseys, and $5.36 +/- 0.34 for pastured Jerseys; effects of breed were significant but treatment, season, and interactions were not. Economic factors such as labor for animal care, manure handling, forage management, and cow culling rates favored pastured cows. Higher fertility and lower mastitis among Jerseys partially offsets lower income over feed cost compared with Holsteins. Milk production was lower in this study for pasture-based systems but lower feed costs, lower culling costs, and other economic factors indicate that pasture-based systems can be competitive with confinement systems.

Animal Feed↗

PubMed2002

Reproduction, mastitis, and body condition of seasonally calved Holstein and Jersey cows in confinement or pasture systems.

Dairy cows in confinement and pasture-based feeding systems were compared across four spring-calving and three fall-calving replicates for differences in reproduction, mastitis, body weights, and body condition scores. Feeding systems and replicates included both Jersey and Holstein cows. Cows in confinement were fed a total mixed ration, and cows on pasture were supplemented with concentrates and provided baled hay or haylage when pasture supply was limiting. Breeding periods were for 75 d in spring or fall. Reproductive performance did not differ significantly due to feeding system or season. Jerseys had higher conception rates (59.6 vs. 49.5 +/- 3.3%) and higher percentages of cows pregnant in 75 d (78.1 vs. 57.9 +/- 3.9%) than Holsteins. Cows in confinement had 1.8 times more clinical mastitis and eight times the rate of culling for mastitis than did cows on pasture. Jerseys had half as many clinical cases of mastitis per cow as Holsteins. Only 41 +/- 5% of confinement Holsteins remained for a subsequent lactation, starting within the defined calving season compared with 51 +/- 5% of pastured Holsteins and 71 and 72 +/- 5% of Jerseys, respectively. Body weights and condition scores were generally higher for confinement cows than pastured cows, and Jerseys had higher condition scores and lower body weights than Holsteins. In summary, pastured cows had fewer clinical cases of mastitis, lower body condition scores, and lower body weights than confinement cows. Holsteins were less likely to rebreed, had more mastitis, higher culling rates, and lower body condition scores than Jerseys.

Animal Feed↗

PubMed2001

Statistical aspects of quantitative image analysis of beta-amyloid in the APP(V717F) transgenic mouse model of Alzheimer's disease.

Cerebral beta-amyloidosis is a central part of the neuropathology of Alzheimer's disease (AD). Quantitation of beta-amyloid plaques in the human AD brain, and in animal models of AD, is an important study endpoint in AD research. Methodologic approaches to the measurement of beta-amyloid in the brain vary between investigators, and these differences affect outcome measures. Here, one quantitative approach to the measurement of beta-amyloid plaques in brain sections was analyzed for sources of variability due to sampling. Brain tissue was from homozygous APP(V717F) transgenic male mice. Sampling variables were at the mouse and microscopic slide and field levels. Results indicated that phenotypic variability in the mouse sample population was the largest contributor to the standard error of the analyses. Within each mouse, variability between slides or between fields within slides had smaller effects on the error of the analyses. Therefore, when designing studies of adequate power, in this and in other similar models of cerebral beta-amyloidosis, sufficient numbers of mice per group must be included in order for change in mean plaque burden attributable to an experimental variable to outweigh phenotypic variability.

Alzheimer Disease↗

PubMed2001

Recovery from transport and acclimatisation of competition horses in a hot humid environment.

The aims of the present field-based study were to investigate changes in fit horses undergoing acclimatisation to a hot humid environment and to provide data on which to base recommendations for safe transport and acclimatisation. Six horses (age 7-12 years) were flown from Europe to Atlanta and underwent a 16 day period of acclimatisation. Exercise conditions during acclimatisation (wet bulb globe temperature index 27.6+/-0.0 [mean +/- s.e.]) were more thermally stressful compared with the European climate from which the horses had come (22.0+/-1.8, P<0.001). Following the flight, weight loss was 4.1+/-0.8% bodyweight and took around 7 days to recover. Water intake during the day was significantly increased (P<0.05) compared with night during acclimatisation. Daily mean exercise duration was 72+/-12 min and the majority of work was performed with a heart rate below 120 beats/min. Respiratory rate (fR) was increased (P<0.05) throughout acclimatisation compared with in Europe, but resting morning (AM) and evening (PM) rectal temperature (TREC), heart rate (fC) and plasma volume were unchanged. White blood cell (WBC) count was significantly increased at AM compared with in Europe on Days 4 and 10 of acclimatisation (P<0.01), but was not different by Day 16. In conclusion, horses exposed to hot humid environmental conditions without prior acclimatisation are able to accommodate these stresses and, with appropriate management, remain fit and clinically healthy, without significant risk of heat illness or heat-related disorders, provided they are allowed sufficient time to recover from transport, acclimatisation is undertaken gradually and they are monitored appropriately.

Acclimatization↗

PubMed2001

Comparison of fatty acid content of milk from Jersey and Holstein cows consuming pasture or a total mixed ration.

Holstein (n = 19) and Jersey (n = 18) cows were used to study effects of two feeding systems on fatty acid composition of milk. Confinement cows were fed a total mixed ration with corn silage and alfalfa silage and pastured cows grazed a crabgrass (90%) and clover (10%) pasture and were allowed 5.5 kg of grain per head daily. Two milk samples were collected from each cow at morning and afternoon milkings 1 d each week for four consecutive weeks in June and July 1998. One set of milk samples was analyzed to determine fatty acid composition, and the second set was used for crude protein and total fat analyses. Data were analyzed by the general linear models procedure of SAS, using a split-plot model with breed, treatment, and breed x treatment as main effects and time of sampling and week as subplot effects along with appropriate interactions. Milk from pastured cows was higher than milk from confinement cows for the cis-9, trans-11 octadecadienoic acid isomer of conjugated linoleic acid (CLA). Also, milk from Holsteins was higher than milk from Jerseys for C16:1, C18:1, and CLA and lower than Jerseys for C6:0, C8:0, C10:0, C12:0, and C14:0. Several treatment x week interactions existed, but main effects were still important; for example, proportions of CLA in milk of grazed cows were relatively constant across weeks (0.66, 0.64, 0.64, and 0.69% +/- 0.02%, respectively), but the CLA in milk of confinement cows increased in wk 4 (0.35, 0.31, 0.31, and 0.48% +/- 0.02% for wk 1 to 4, respectively). There are potentially important differences in fatty acid composition of milk from cows consuming a warm season pasture species compared with milk from cows consuming a total mixed ration, as well as differences between Holstein and Jersey breeds.

Animal Feed↗

PubMed2000

The inheritance of mitochondrial DNA heteroplasmy: random drift, selection or both?

The mammalian mitochondrial genome (mtDNA) is a small double-stranded DNA molecule that is exclusively transmitted down the maternal line. Pathogenic mtDNA mutations are usually heteroplasmic, with a mixture of mutant and wild-type mtDNA within the same organism. A woman harbouring one of these mutations transmits a variable amount of mutant mtDNA to each offspring. This can result in a healthy child or an infant with a devastating and fatal neurological disorder. Understanding the biological basis of this uncertainty is one of the principal challenges facing scientists and clinicians in the field of mitochondrial genetics.

Animals↗

PubMed2000

BBID: the biological biochemical image database.

The Biological Biochemical Image Database is a WWW accessible relational database of archived images from research articles that describe regulatory pathways of higher eukaryotes. Pathway information is annotated and can be queried in the study of complex gene expression. In this way, complex regulatory pathways can be tested empirically in an efficient manner in the context of large-scale gene-expression systems.

Computer Graphics↗

PubMed2000

Towards reliable prenatal diagnosis of mtDNA point mutations: studies of nt8993 mutations in oocytes, fetal tissues, children and adults.

Prenatal diagnosis of mitochondrial DNA (mtDNA) mutations is technically possible, but has only rarely been attempted. This is largely because of uncertainty about the effects of mtDNA heteroplasmy, the mtDNA bottleneck, random segregation or selection of mtDNA species, and difficulty in correlating a particular mtDNA mutant load with clinical outcome. We have investigated the feasibility of prenatal diagnosis for two common mtDNA mutations at nucleotide (nt)8993 by determining mtDNA mutant loads in human oocytes and by reviewing data on 56 pedigrees with these mutations, and by reviewing six studies on mtDNA mutations in human fetuses. Data from heteroplasmic human and mouse oocytes demonstrate that the bottleneck occurs in early oogenesis. Analysis of mutant loads of the nt8993 mutations in fetal and adult tissues confirms that there is no substantial tissue variation, implying that the mutant load in a prenatal sample will represent the mutant load in other fetal tissues. The two nucleotide 8993 mutations each show a strong correlation between mutant load and symptom severity and between maternal blood mutant load and risk of a severe outcome. We generated empirical data for calculating recurrence risk and predicting the clinical outcome of a given mutant load. These predictive data can be used (cautiously) for genetic counselling and prenatal diagnosis of nucleotide 8993 mutations.

Adult↗