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E R Martin

Publications and source records attributed to E R Martin.

At least 55 records · Page 3Linked to original sources
PubMed1999

Analysis of association between Alzheimer disease and the K variant of butyrylcholinesterase (BCHE-K).

Butyrylcholinesterase (BCHE) is an enzyme expressed in most human tissues. Recently, an increased odds of carrying the K variant of BCHE (BCHE-K) was reported among Alzheimer disease (AD) cases as compared with controls. We tested our data set of 245 sporadic AD cases and 241 controls for an association between BCHE-K, APOE4, and AD using logistic regression and chi-square analyses. The sib transmission disequilibrium test (S-TDT) was also used to test for differences in BCHE-K allele frequencies between 163 discordant sib-pairs selected from multiplex AD families. No statistically significant differences were noted between BCHE-K case and control allele frequencies even after stratifying by APOE4 status. S-TDT analysis between the BCHE-K variant and AD was also not significant (P = 0.52). We conclude that BCHE-K is not a major genetic risk factor for AD in our study population.

Adult↗
PubMed1999

Two tests of association for a susceptibility locus for families of variable size: an example using two sampling strategies.

A two-stage approach was used to analyze Problem 2 simulated data from Genetic Analysis Workshop 11. In the first stage, we tested for linkage with the Haseman-Elston test in SIBPAL. Markers that were significant in the first stage were followed up with two types of association tests. These association tests differ in the type of family information used: 1) parental transmissions to affected children or 2) differences in marker allele frequencies between affected and unaffected siblings. We also explored how the conclusions changed when different sampling strategies were used. Of particular interest was whether the entire data set should be used to test for both linkage and association or whether the data set should be halved to allow for replication of the initial association results.

Environment↗
PubMed1999

Complete genomic screen for disease susceptibility loci in nuclear families.

We performed genome-wide model dependent and independent analyses on a simulated data set of 400 families segregating for a rare disorder. Regions on chromosomes 1, 3, and 5 were consistently indicated across the various analyses performed. Follow-up analyses included stratification for locus heterogeneity and clinical phenotype and studies of gene x gene and gene x environment interaction. The region around D1G024 was most notable, showing strong association and linkage with the trait. We also identified regions D3G043-46 and D5G037-39 by strong linkage and association findings and region D1G001-09 by linkage analysis. A complex statistical interaction was suggested between D1G024, D3G046 and environmental factor 1. This report suggests that traditional methods of analysis can be implemented to analyze and describe the mechanisms that may underlie the more complex genetic disorders.

Chromosome Mapping↗
PubMed1999

Sibling-based tests of linkage and association for quantitative traits.

The transmission/disequilibrium test (TDT) developed by Spielman et al. can be a powerful family-based test of linkage and, in some cases, a test of association as well as linkage. It has recently been extended in several ways; these include allowance for implementation with quantitative traits, allowance for multiple alleles, and, in the case of dichotomous traits, allowance for testing in the absence of parental data. In this article, these three extensions are combined, and two procedures are developed that offer valid joint tests of linkage and (in the case of certain sibling configurations) association with quantitative traits, with use of data from siblings only, and that can accommodate biallelic or multiallelic loci. The first procedure uses a mixed-effects (i.e., random and fixed effects) analysis of variance in which sibship is the random factor, marker genotype is the fixed factor, and the continuous phenotype is the dependent variable. Covariates can easily be accommodated, and the procedure can be implemented in commonly available statistical software. The second procedure is a permutation-based procedure. Selected power studies are conducted to illustrate the relative power of each test under a variety of circumstances.

Genetic Linkage↗
PubMed1999

Aging alters properties of the circadian pacemaker controlling the locomotor activity rhythm in males of Drosophila nasuta.

Effects of aging on the circadian rhythm of locomotor activity in males of Drosophila nasuta were investigated. The adult life of males was divided in 1-3 stages according to spontaneous changes in free-running period tau in constant darkness (DD): stage 1, days 1-19; stage 2, days 20-36; stage 3, days 37-43. Stage 1 was characterized by a bimodal activity pattern with a short light-induced morning peak and a prolonged evening peak when the flies were entrained to light-dark cycles of 12 hours of light, 12 hours of darkness (LD 12:12). The morning peak had a phase angle difference psi m (psi, the time from lights on in LD 12:12 cycles to the onset of morning peak) of about 0.1 h, while psi e (psi of evening peak) was about 9 h at stage 1. The transient morning peak was curtailed at the end of stage 1. At stage 2, the psi e was about 10 h, and the activity end was delayed by an addition of about 3 h of activity in the scotophase. The changes in tau during DD free runs were determined in two groups of flies: flies reared in LD 12:12 and flies reared in DD. In both groups, tau increased from about 23 h at stage 1 to about 25 h at stage 2. Stage 3 was characterized by arrhythmicity associated with highest mean activity level (total number of passes/fly/day) in the entrained and both free-running groups. The mean activity level increased significantly from stage 1 to stage 3 in all three groups of flies.

Aging↗
PubMed1999

Public health professionals in the Midwest: a profile of connectivity and information technology skills.

OBJECTIVES: The aim of this study was to assess Internet connections and information technology skills of public health workers in the Midwest. METHODS: A questionnaire was mailed to 713 local health departments (LHDs) in the ten states of the Greater Midwest Region. RESULTS: Three hundred forty-four LHDs (48%) responded. Overall, 85% own a computer that would allow Internet access. Half provide Internet access to some or all staff. Of these, two-thirds use e-mail and half search the Web. One-half are linked to the State Health Department, and 30% are linked to other local health departments. Over half use CDC-Wonder; less than 20% search MEDLINE. Two-thirds of the respondents expressed an interest in MEDLINE training, and three-fourths are interested in learning more about the Internet. Sixty-nine percent of respondents planned to enhance electronic communication capacity within the next year. CONCLUSIONS: Public health practitioners need timely, convenient access to information to aid them in improving the health of the American public. A majority of public health departments in the Midwest are technically capable of connecting to the Internet. This technological capability, combined with an expressed desire by public health agencies to have workers become computer literate, suggests an important role for health sciences librarians.

Computer Literacy↗
PubMed1998

Marker selection for the transmission/disequilibrium test, in recently admixed populations.

Recent admixture between genetically differentiated populations can result in high levels of association between alleles at loci that are <=10 cM apart. The transmission/disequilibrium test (TDT) proposed by Spielman et al. (1993) can be a powerful test of linkage between disease and marker loci in the presence of association and therefore could be a useful test of linkage in admixed populations. The degree of association between alleles at two loci depends on the differences in allele frequencies, at the two loci, in the founding populations; therefore, the choice of marker is important. For a multiallelic marker, one strategy that may improve the power of the TDT is to group marker alleles within a locus, on the basis of information about the founding populations and the admixed population, thereby collapsing the marker into one with fewer alleles. We have examined the consequences of collapsing a microsatellite into a two-allele marker, when two founding populations are assumed for the admixed population, and have found that if there is random mating in the admixed population, then typically there is a collapsing for which the power of the TDT is greater than that for the original microsatellite marker. A method is presented for finding the optimal collapsing that has minimal dependence on the disease and that uses estimates either of marker allele frequencies in the two founding populations or of marker allele frequencies in the current, admixed population and in one of the founding populations. Furthermore, this optimal collapsing is not always the collapsing with the largest difference in allele frequencies in the founding populations. To demonstrate this strategy, we considered a recent data set, published previously, that provides frequency estimates for 30 microsatellites in 13 populations.

Alleles↗
PubMed1998

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group.

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.

Alleles↗
PubMed1998

Consumer health informatics: the medical librarian's role.

Growing consumer interest in health-related information has created a need for professionals to manage, provide, and interpret such material. In preparing for the new demands of the market, HIM professionals can learn from the example of medical librarians, who are already working to meet those needs.

Computer Communication Networks↗
PubMed1997

A Monte Carlo permutation approach to choosing an affection status model for bipolar affective disorder.

A permutation test is proposed for assessing affection status models. The test uses marker data from regions with prior evidence of linkage to susceptibility genes, and three different test statistics are examined. We applied the test to the GAW10 data and found no evidence on chromosome 18 to reject the affection status model that groups individuals diagnosed with either bipolar I, bipolar II or unipolar. The chromosome 5 data gave similar results, and further suggested that individuals diagnosed with unipolar-single episode not be included as affected. A preliminary power study suggested that one of the proposed statistics, S, is to be preferred in certain circumstances.

Bipolar Disorder↗
PubMed1997

Tests for linkage and association in nuclear families.

The transmission/disequilibrium test (TDT) originally was introduced to test for linkage between a genetic marker and a disease-susceptibility locus, in the presence of association. Recently, the TDT has been used to test for association in the presence of linkage. The motivation for this is that linkage analysis typically identifies large candidate regions, and further refinement is necessary before a search for the disease gene is begun, on the molecular level. Evidence of association and linkage may indicate which markers in the region are closest to a disease locus. As a test of linkage, transmissions from heterozygous parents to all of their affected children can be included in the TDT; however, the TDT is a valid chi2 test of association only if transmissions to unrelated affected children are used in the analysis. If the sample contains independent nuclear families with multiple affected children, then one procedure that has been used to test for association is to select randomly a single affected child from each sibship and to apply the TDT to those data. As an alternative, we propose two statistics that use data from all of the affected children. The statistics give valid chi2 tests of the null hypothesis of no association or no linkage and generally are more powerful than the TDT with a single, randomly chosen, affected child from each family.

Alleles↗
PubMed1997

Power studies for the transmission/disequilibrium tests with multiple alleles.

Case-control studies compare marker-allele distributions in affected and unaffected individuals, and significant results suggest linkage but may simply reflect population structure. For markers with m alleles (m > or = 2), a McNemar-like statistic, I, estimates the level of population association between marker and disease loci. To test for linkage after significant case-control tests, within-family tests are performed. These operate on the contingency table, with i, jth element equal to the number of parents that transmit marker allele Mi and do not transmit marker allele Mi to an affected offspring. The dimension of the table is the number of alleles at the marker locus. Three test statistics have recently been proposed in the literature: Tc compares symmetric pairs of cells (i, j) and (j, i), Tm compares row and column totals for the same marker allele, and a likelihood ratio statistic Tl uses all the cells in the table. In addition, we consider a new statistic, Tmhet, that uses only the heterozygous parents and is approximately chi2 with (m - 1) df. We use a Monte Carlo test to guarantee valid tests and to demonstrate the inferiority of Tc and the equality of Tm and Tl in terms of power. The power of the Tmhet test is close but not always equal to the power of the Tm test. We also show that under the alternative hypothesis of linkage, Tm is approximately noncentral chi2 with (m - 1) df and noncentrality parameter 2NT(1 - 2theta)2I*, when data on single affecteds in NT families are used. If the disease has a low population frequency, then I* is estimated using the case-control statistic I. This offers a basis for choosing sample size, or choosing a marker system.

Alleles↗
PubMed1997

Delivering health information services and technologies to urban community health centers: the Chicago AIDS Outreach Project.

Health professionals cannot address public health issues effectively unless they have immediate access to current biomedical information. This paper reports on one mode of access, the Chicago AIDS Outreach Project, which was supported by the National Library of Medicine through outreach awards in 1995 and 1996. The three-year project is an effort to link the programs and services of the University of Illinois at Chicago Library of the Health Sciences and the Midwest AIDS Training and Education Center with the clinic services of community-based organizations in Chicago. The project was designed to provide electronic access to AIDS-related information for AIDS patients, the affected community, and their care givers. The project also provided Internet access and training and continued access to library resources. The successful initiative suggests a working model for outreach to health professionals in an urban setting.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Networking consumer health information: bringing the patient into the medical information loop.

The Library of the Health Sciences at the University of Illinois at Chicago obtained a grant from the Illinois State Library to implement a statewide demonstration project that would provide consumer health information (CHI) using InfoTrac's Health Reference Center CD-ROM database. The goals of the project were to cooperate with targeted public libraries and clinics in providing CHI at the earliest point of need; to provide access to the database via a dial-up network server and a toll-free telephone number; and to work with targeted sites on database training, core CHI reference sources, and referral procedures. This paper provides background information about the project; describes the major systems and technical issues encountered; and discusses the outcomes, impact, and envisioned enhancements.

CD-ROM↗
PubMed1995

Delivering medical information to the desktop: the UIC GRATEFUL-MED-via-the-Internet experience.

The University of Illinois at Chicago (UIC) provides the campus community, including the main campus and three regional sites, with a local MEDLINE option through a GRATEFUL MED fixed-fee licensing agreement with the National Library of Medicine. Searching is available via the Internet. A password server and customized GRATEFUL MED clients were built in order to adapt this off-the-shelf product to match the look and feel of other UIC campus-wide Internet resources. Installation, documentation, and training issues affecting the success of the project are discussed.

Chicago↗
PubMed1994

Database search services as a basic service in academic health sciences libraries.

Mediated search services, usually offered for a fee, are commonplace in academic health sciences libraries. At the same time, users of these services have numerous self-service options available to them; for example, CD-ROMs and locally mounted databases. In keeping with its philosophy of access to rather than ownership of information, the University of Washington Health Sciences Library and Information Center (HSLIC) changed its policy from charging clients for mediated searching to offering mediated searches as an essential service of the library. By taking this step, HSLIC moved closer to becoming a true "library without walls." This paper describes HSLIC's experience with changing its policy and examines the issues surrounding use of the collection budget to subsidize access to online information in academic health sciences libraries.

CD-ROM↗
PubMed1990

Heterogeneity of cell surface endothelin receptors.

Two distinct cell surface endothelin receptors were identified, namely a 73-kDa protein referred to as ET-R1 and a 60-kDa protein named ET-R2. ET-R1 was expressed as the sole endothelin receptor on rat A10 vascular smooth muscle cells and C6 glial cells. Binding of 125I-ET-1 to these cells was inhibited by 50-200 pM endothelin-1 and -2, whereas endothelin-3 did not compete for this receptor subtype. Binding of 125I-ET-1 to intact A10 and C6 cells was reversible, indicating that ET-R1 is located on the cell surface. Affinity labelling of a single 73-kDa band on sodium dodecyl sulfate-polyacrylamide gels by 125I-ET-1 in A10 and C6 cells was inhibited by endothelin-1 but not by endothelin-3. In A10 cells, endothelin-1 but not endothelin-3 elicited a concentration-dependent increase in intracellular inositol trisphosphate levels. ET-R1 was also expressed in cultured rat glomerular mesangial cells based on findings of a subset of receptors with an apparent molecular mass of 73 kDa that bound 125I-ET-1 displacable by endothelin-1 and endothelin-2 but not by endothelin-3. These cells also expressed the ET-R2 receptor subtype, based on findings of a 60-kDa binding site that could be labeled by both 125I-ET-1 and 125I-ET-3. Labeling of ET-R2 by the radioactive endothelins-1 and -3 was inhibited competitively by endothelins-1, -2, and -3. Furthermore, ET-R2 was shown to be a functional receptor, as endothelin-3 caused inositol trisphosphate levels to rise in mesangial cells. An endothelin binding site with high affinity for endothelin-3 was also identified on rat PC12 pheochromocytoma cells, although the apparent molecular mass of this receptor could not be verified by cross-linking studies. Since endothelin-1 or -3 failed to augment inositol trisphosphate levels in these cells, this binding site could represent a third endothelin receptor subtype. Thus, two distinct functional receptors for endothelins were identified on rat cells, namely the 73-kDa ET-R1 which has an exceedingly low affinity for endothelin-3 and the 60-kDa ET-R2 which binds endothelin-3 with high affinity. Whether an additional endothelin receptor subtype exists in PC12 cells remains to be shown with certainty.

Animals↗