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R Elston

Publications and source records attributed to R Elston.

17 recordsLinked to original sources
PubMed2000

Discovery of a Color-selected Quasar at z = 5.50.

We present observations of RD J030117+002025, a quasar at z=5.50 discovered from deep, multicolor, ground-based observations covering 74 arcmin2. This is the most distant quasar or active galaxy currently known. The object was targeted as an R-band dropout, with RAB>26.3 (3 sigma limit in a 3&arcsec; diameter region), IAB=23.8, and zAB=23.4. The Keck/Low-Resolution Imaging Spectrometer spectrum shows broad Lyalpha/N v lambda1240 emission and sharp absorption decrements from the highly redshifted hydrogen forests. The fractional continuum depression due to the Lyalpha forest is DA=0.90. RD J030117+002025 is the least luminous high-redshift quasar known (MB approximately -22.7).

Journal Article↗
PubMed1999

Integrated designs for gene discovery and characterization.

Recent advances, including near completion of the human genome map, ever improving high-throughput technologies, and successes in discovering chronic disease-related genes, have stimulated the further development of genetic epidemiology. The primary mission of genetic epidemiology is to discover and characterize genes, whether independent of or interactive with environmental factors, that cause human diseases. To accomplish such a mission, genetic epidemiology needs to integrate both genetic and epidemiologic approaches. One of the challenges facing such an integrated approach is the identification of study designs that are efficient for both gene discovery and characterization. Because designs for gene discovery alone and designs for gene characterization alone have been elaborated in the other two panels, the focus of this paper is to describe those designs that may be useful for discovery and characterization jointly, including case-family and case-control-family designs. Examples of integrated designs are described, and studies of breast cancer conducted at the Fred Hutchinson Cancer Research Center are used for illustration. Finally, related analytic issues are also discussed.

Breast Neoplasms↗
PubMed1998

Interaction of the apolipoprotein E and CI loci in predisposing to late-onset Alzheimer's disease.

OBJECTIVE: The association between Alzheimer's disease (AD) and alleles at the ApoE and the ApoCI loci were tested. BACKGROUND: The ApoE alleles, in linkage disequlibrium with ApoCI alleles, have been reported as associated with (epsilon4) or protective for (epsilon2) AD. METHODS: The patients comprise two samples, with a total of 176 whose diagnosis has been confirmed as having probable AD and 226 controls. Genomic DNA was extracted from blood or transformed lymphocytes. Logistic regression was used to determine the effects of alleles at the ApoE and ApoCI loci after allowing for the effects of age and gender. RESULTS: The effects of the ApoE epsilon2, epsilon3, and epsilon4 alleles were individually studied first; ignoring the ApoCI locus, only the dominant or additive effect of epsilon4 is significant after considering age, gender, and sample--the dominant effect being slightly more significant. The effect of epsilon4 (when only the ApoE locus is included in the model) was larger than recently reported: the odds ratio was 5.57 (95% CI, 3.46 to 8.98). Similarly, when the ApoCI locus was examined, ignoring the ApoE locus, a dominant effect of A was found to be slightly more significant than an additive effect. Finally, models were considered that included the dominant effect of epsilon4, the dominant effect of A, and their interaction. A model that included only the interaction of ApoE and ApoCI yielded the largest odds ratio, 5.89 (95% CI, 3.64 to 9.53). CONCLUSIONS: Association of AD with both the ApoE epsilon4 and ApoCI A alleles was found. The increased risk of AD among carriers of epsilon4 was found to be higher among those who also bear the ApoCI A allele but this may be due to a dose effect of the epsilon4 allele.

Age of Onset↗
PubMed1994

Interaction of the E6 protein of human papillomavirus with cellular proteins.

The E6 proteins of the oncogenic Human Papillomavirus (HPV) types 16 and 18 are known to bind two cellular proteins, the tumor suppressor protein p53 and a 100 kDa protein named E6-AP. In this paper we describe the expression and purification of biologically active E6 fusion proteins and their specific association with additional cellular proteins. HPV16E6 specifically associated with at least seven cellular proteins which have been designated pp212, pp182, p100, p81, p75, p53 and p33 respectively, on the basis of molecular mass and phosphorylation. We have also shown that the complex of cellular proteins associated with HPV16, 18, 6 and 11 E6 proteins contains a protein kinase. This protein kinase phosphorylated exogenous histone H1 and the E6 associated protein pp182.

Papillomaviridae↗
PubMed1991

Allergic rhinoconjunctivitis and contact lens intolerance.

To investigate whether underlying rhinoconjunctivitis contributes to contact lens intolerance, we surveyed 885 contact lens wearers by questionnaire. Allergic rhinoconjunctivitis was defined as the presence of nasal symptoms and positive skin tests for inhalant allergens (definite allergy group). Subjects with nasal symptoms and positive family history of atopy or seasonality of symptoms were grouped under presumptive allergy. Absolute intolerance (AI) was defined as abandoning lenses and wearing glasses. Partial intolerance (PI) was defined as changing lenses or cleaning solutions to alleviate eye discomfort. Seventy-six percent of those with allergy exhibited AI or PI as compared to 60% of those with no allergy. Furthermore, the frequency of seasonal exacerbation of eye symptoms when using contact lenses was significantly higher in subjects with allergy compared to those without allergy (spring, 49% vs. 19%, P less than .0001; summer, 35% vs. 20%, P less than .001; fall, 27% vs. 12%, P less than .0001). We conclude that underlying allergic rhinoconjunctivitis may contribute to contact lens intolerance.

Adult↗
PubMed1989

Aerosol bronchodilator delivery methods. Relative impact on pulmonary function and cost of respiratory care.

Thirty-six acutely III, hospitalized patients with acute exacerbations of obstructive airway disease and a greater than 10% increase in forced expiratory volume in 1 s after administration of aerosolized bronchodilator were randomized to receive either metaproterenol sulfate delivered by updraft-compressor nebulization (UDN) or terbutaline sulfate delivered by metered-dose inhaler (MDI) with a spacer. Serial analyses of pulmonary function measurements were performed with the use of 95% confidence intervals for the percentage response ratios of MDI to UDN. The response to MDI was at least equivalent to that of UDN, and MDI use was associated with no prolongation of hospital stay. Equivalent bronchodilation was achieved with MDI therapy with a lower daily charge for therapy for each patient and less respiratory therapist time. In hospitalized bronchodilator-responsive patients with acute exacerbations of obstructive airway disease, the MDI/spacer combination is the preferred approach when the status of the patient allows its use.

Aerosols↗
PubMed1989

Segregation and linkage analyses of bipolar and major depressive illnesses in multigenerational pedigrees.

Data were collected on six large multigenerational pedigrees, four ascertained through a proband with major depression and two ascertained through a proband with a bipolar form of illness. Diagnoses were made using the SADS-L structured interview and Research Diagnostic Criteria (RDC). Complex segregation analyses were conducted on the bipolar and the major depression pedigree sets using a model allowing for both major locus and polygenic inheritance; in these analyses a variety of diagnostic schemes and assumptions concerning the lifetime population prevalence were examined. Linkage analyses on standard markers were conducted using parameters for transmission of susceptibility to illness derived from the segregation analyses. Results of the segregation analyses were quite sensitive to the diagnostic and prevalence assumptions. In the pedigrees ascertained through probands with a bipolar form of illness, we were unable to discriminate between major gene and polygenic inheritance. The data were compatible with Mendelian major gene transmission of susceptibility to illness when bipolar and schizoaffective manic diagnoses were considered as affected and the lifetime population prevalence was between 0.04 and 0.06. Outside this narrow prevalence range, or when additional diagnoses, such as major depression or hypomania, were included as expressions of liability to disease, major gene transmission of susceptibility to disease could be rejected. Similarly, in the pedigrees ascertained through probands with major depression, it was not generally possible to discriminate between major gene and polygenic transmission of susceptibility to illness. For a diagnostic scheme including only major depression as a manifestation of susceptibility to illness, there was a narrow range of lifetime population prevalence values (female prevalence ranging from 0.20 to 0.25, male prevalence set to 1/2 female prevalence) which yielded results compatible with major gene transmission. Linkage analyses for all markers yielded negative or inconclusive results. In one bipolar pedigree a lod score of 1.65 was found with a marker in chromosome 1 recommending further studies of this chromosome.

Adult↗
PubMed1985

A study of multiple biological markers in twins.

Genetic and environmental influences on the phenotypic expressions of several biological markers were studied in 18 monozygous (MZ) and 8 dizygous (DZ) twin pairs. Zygosity was determined using ABO, Rh, and HLA. The biomarkers studied included: T & B lymphocytes, suppressor and helper T lymphocytes (T gamma, T mu), T cell (PHA) mitogen activation (MA), serum immunoglobulins (IgA, IgM, and IgG), plasma carcinoembryonic antigen (CEA), aryl-hydrocarbon hydroxylase (AHH) and sister chromatid exchange (SCE) in lymphocytes. Temporal variation of markers over a 6-month period was not significant. The mean absolute differences between levels from first and second blood draws were less than one standard deviation. Variability associated with age was not significant. Females had higher levels of T lymphocytes than males. A gender related association was observed for the IgM immunoglobulin test: females had a higher mean level of IgM. Smoking was found to influence the levels of SCE, T helper lymphocytes and mitogen activation. The variability of these biomarkers within and between twin pairs was quantified. Immunoglobulin levels, particularly that of IgM, showed statistically greater similarity within MZ twins than within DZ twins. Several other markers suggested heritability.

Adult↗
PubMed1984

Search for biological/genetic markers in a long-term epidemiological and morbid risk study of affective disorders.

A long-term epidemiological genetic study was conducted in which all new patients were evaluated prospectively at the Foundation for Depression and Manic Depression and two Lithium/Affective Disorders clinics at the Columbia-Presbyterian Medical Center between the years of 1972 and 1978. All patients met Feighner, RDC and DSM III criteria for Major Depressive Disorder after initial clinical screening interviews and were further subtyped using the Fieve-Dunner 7-point criteria. All 604 probands and 90% of 2711 first-degree relatives were interviewed blindly by diagnosticians trained in the use of the SADS structured interview. Cumulative morbid risk in parents, siblings and children of 490 bipolar probands was 15.6 +/- 3% and 14.0 +/- 1.7% in the first-degree relatives of 114 unipolar probands. A number of biological and genetic marker studies were simultaneously performed on samples of the overall population. The enzymes catechol O-methyltransferase and dopamine beta-hydroxylase, and the dexamethasone suppression test (SDT) did not show any biological marker value for outpatients even though both enzymes were determined to have hereditability. The HLA system, monoamine oxidase and acetylcholinesterase segregated differently from normal controls in samples of the patient population. The positive association findings with monoamine oxidase and the HLA system conflicted with the positive findings of other investigators, leaving doubtful their biological marker value. Red cell acetylcholinesterase was found to be significantly lower in affective disorder patients than in controls. This positive association finding was recently replicated by Mathews et al. (1982) but needs further confirmation. Using 28 blood group markers, a prior association study between the trait defining susceptibility to affective disorder and the genetic marker was positive for haptoglobin GC, and properdinfactor B, confirming earlier findings. Using the sib-pair method on the remaining 25 blood groups revealed that none other than peptidase A showed significant linkage with affective disorder since one significant finding is expected by chance. We conclude from the overall morbid risk data and segregation analyses that bipolar manic-depressive illness is a spectrum disease inherited through a multifactorial mode of genetic transmission (which is not synonymous with polygenetic inheritance) with possible genetic heterogeneity and find no evidence for X-linkage. Additional studies with acetylcholinesterase, haptoglobin, GC, and properdin-factor B are needed to confirm their positive biological/genetic marker value suggested by our long-term epidemiological study.

Acetylcholinesterase↗
PubMed1983

Abnormal estrogen conjugation in women at risk for familial breast cancer at the periovulatory stage of the menstrual cycle.

The present study was designed to establish whether women with a family history of breast cancer exhibit endocrine abnormalities which could be responsible for their increased risk for the disease. Plasma hormone levels were measured every second day throughout the menstrual cycle in 30 women at risk for familial breast cancer and in an equal number of matched controls. Thirteen of the 14 substances measured exhibited no differences between the two populations, but plasma androsterone sulfate was significantly lower in the high-risk subjects. Thirteen urinary hormones were measured every day throughout the cycle with only the mean estrone and estradiol glucuronide but not estriol glucuronide content being significantly lower in the high-risk subjects. A compensatory increase in the urinary estrogen sulfates was observed. Daily analysis of these differences showed that they were most pronounced in thry day throughout the cycle with only the mean estrone and estradiol glucuronide but not estriol glucuronide content being significantly lower in the high-risk subjects. A compensatory increase in the urinary estrogen sulfates was observed. Daily analysis of these differences showed that they were most pronounced in thry day throughout the cycle with only the mean estrone and estradiol glucuronide but not estriol glucuronide content being significantly lower in the high-risk subjects. A compensatory increase in the urinary estrogen sulfates was observed. Daily analysis of these differences showed that they were most pronounced in the periovulatory period of the cycle. These results suggest that the genetic risk for breast cancer is associated with an abnormality in estrogen conjugation at a specific time of the ovulatory cycle.

Androgens↗
PubMed1981

Prolonged survival as a component of a hereditary breast and nonpolyposis colon cancer.

Identification of prolonged survival in hereditary breast and colon cancer (exclusive of familial multiple adenomatous polyposis coli) have been shown to be statistically significant (P less than .05) when compared to the American College of Surgeons Tumor Registry for these respective neoplasms. Our hypothesis is that the genotype in hereditary cancer determines both susceptibility and natural history, such that increased survival is a manifestation of the natural history.

Biological Evolution↗