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Biomedical subjects

E A Thompson

Publications and source records attributed to E A Thompson.

At least 109 records · Page 6Linked to original sources
PubMed1990

Transvaginal sonography as a screening method for ovarian cancer. A report of the first 1000 cases screened.

From November 1987 to April 1989, 1000 women 40 years or older underwent screening vaginal sonography at the University of Kentucky Medical Center (Lexington, KY). Patients included in this investigation were all asymptomatic and had no known pelvic abnormalities. Each ovary was measured in three planes and ovarian volume was calculated using the prolate ellipsoid formula. The upper limit of normal for ovarian volume was 18 cm3 in premenopausal women and 8 cm3 in postmenopausal women. In patients with normal scans, mean ovarian volumes decreased from 6.8 cm3 to 3.0 cm3 with menopause. Thirty-one patients (3.1%) had abnormal vaginal sonograms and 24 underwent exploratory laparotomy. All patients undergoing surgery had ovarian or fallopian tube tumors with dimensions identical to those predicted by ultrasound. Histologic diagnoses of these tumors included the following: adenocarcinoma, one, serous cystadenoma, eight; endometrioma, six; and cystic teratomas, two. Vaginal sonography was performed easily and without complications, and was well accepted by patients. All patients with normal sonograms have been rescreened annually and none have subsequently developed ovarian cancer. Further clinical trials to determine the efficacy of vaginal sonography as a screening method for ovarian cancer are indicated.

Adult↗
PubMed1990

Interobserver variation in ovarian measurements using transvaginal sonography.

Ultrasound examination of ovarian size and morphology has been proposed as a screening method for ovarian carcinoma. A screening test must give consistent results when performed by different examiners to reliably determine the sensitivity and specificity of the test. This study was designed to evaluate interobserver variation in ovarian size measurements using transvaginal sonography. Two examiners independently measured 86 ovaries in three planes and ovarian volumes were calculated using the prolate ellipsoid formula. The correlation coefficient between the ovarian volume measurements made by each examiner was 0.960. These results indicate that interobserver variation in ovarian volume measurements is extremely low as determined by transvaginal sonography.

Adult↗
PubMed1990

Glucocorticoid inhibition of transcription from adenovirus major late promoter.

Glucocorticoids inhibit proliferation of lymphosarcoma P1798 cells in culture. This is accompanied by inhibition of expression of class I as well as some class II genes. We have used the technique of transcription in vitro and the adenovirus major late promoter (AdMLP) to investigate molecular mechanisms of glucocorticoid inhibition of transcription of class II genes. Nuclear extracts from exponentially growing P1798 cells support faithful transcription from AdMLP. However, treatment of P1798 cells with 10(-7) M dexamethasone (a synthetic glucocorticoid) for 24 h impairs the ability of nuclear extracts prepared from such cells to support faithful transcription from AdMLP. Transcription from the human histone H4 gene promoter is unaffected by dexamethasone treatment. Gel mobility shift assays using synthetic oligonucleotide probe indicate no difference in the CAAT box binding activity of control and dexamethasone-treated cell extracts. Similarly, dexamethasone treatment does not affect the upstream stimulatory factor activity of P1798 cells. Furthermore, up-stream stimulatory factor purified from control cell extracts is unable to reconstitute the glucocorticoid-treated cell extracts for transcription from AdMLP. Fractionation of the control cell extracts on Sepharose S yields two protein fractions, neither of which supports transcription from AdMLP. However, one of these fractions, S-II, confers upon glucocorticoid-treated cell extracts the ability to support faithful transcription from AdMLP. We conclude that glucocorticoids regulate the transcription from AdMLP by regulating the activity of a trans-acting transcription factor which copurifies with fraction S-II.

Adenoviridae↗
PubMed1990

R.A. Fisher's contributions to genetical statistics.

R. A. Fisher (1890-1962) was a professor of genetics, and many of his statistical innovations found expression in the development of methodology in statistical genetics. However, whereas his contributions in mathematical statistics are easily identified, in population genetics he shares his preeminence with Sewall Wright (1889-1988) and J. B. S. Haldane (1892-1965). This paper traces some of Fisher's major contributions to the foundations of statistical genetics, and his interactions with Wright and with Haldane which contributed to the development of the subject. With modern technology, both statistical methodology and genetic data are changing. Nonetheless much of Fisher's work remains relevant, and may even serve as a foundation for future research in the statistical analysis of DNA data. For Fisher's work reflects his view of the role of statistics in scientific inference, expressed in 1949: There is no wide or urgent demand for people who will define methods of proof in set theory in the name of improving mathematical statistics. There is a widespread and urgent demand for mathematicians who understand that branch of mathematics known as theoretical statistics, but who are capable also of recognising situations in the real world to which such mathematics is applicable. In recognising features of the real world to which his models and analyses should be applicable, Fisher laid a lasting foundation for statistical inference in genetic analyses.

Animals↗
PubMed1990

Pedigree analysis for quantitative traits: variance components without matrix inversion.

Recent developments in the animal breeding literature facilitate estimation of the variance components in quantitative genetic models. However, computation remains intensive, and many of the procedures are restricted to specialized designs and models, unsuited to data arising from studies of natural populations. We develop algorithms that allow maximum likelihood estimation of variance components for data on arbitrary pedigree structures. The proposed methods can be implemented on microcomputers, since no intensive matrix computations or manipulations are involved. Although parts of our procedures have been previously presented, we unify these into an overall scheme whose intuitive justification clarifies the approach. Two examples are analyzed: one of data on a natural population of Salivia lyrata and the other of simulated data on an extended pedigree.

Algorithms↗
PubMed1989

Glucocorticoid inhibition of gene expression and proliferation of murine lymphoid cells in vitro.

Glucocorticoids inhibit the proliferation of murine T-lymphoma P1798 cells. P1798 cells do not die in the presence of dexamethasone, and the process of inhibition of proliferation is completely reversible. As cells cease to divide, expression of a number of genes is inhibited. Among these are genes the expression of which is regulated in some manner that is linked to cell proliferation. We have undertaken to study the mechanism whereby glucocorticoids inhibit the expression of genes in P1798 cells. Three model systems will be reviewed. In all cases, these appear to be examples of secondary regulation. Glucocorticoid-mediated inhibition of transcription of the DNA encoding ribosomal RNA (rDNA) has been investigated in some detail. The data indicate that dexamethasone causes a decrease in the amount or activity of an RNA polymerase I transcription initiation factor. This factor exhibits a short biological half-life and the data are consistent with the hypothesis that glucocorticoids regulate the synthesis of this transcription factor. The gene encoding thymidine kinase appears to be regulated in a similar fashion. On this basis, we propose that glucocorticoids may have the general property of regulating the synthesis of certain transcription factors. Glucocorticoids also regulate the translation of a certain class of mRNAs, including those that encode ribosomal proteins. These are characterized by a low efficiency of translation in untreated cells. Upon exposure to dexamethasone, the translation of these mRNAs is disproportionately inhibited. We speculate that translation of the mRNAs encoding certain transcription factors may be regulated in a similar fashion. Specifically, we propose that transcription of certain proliferation-related genes may be dependent upon factors of short biological half-life. These are encoded by mRNAs that are poorly translated under optimal growth conditions. Any slight perturbation in translation efficiency, as caused by glucocorticoids, results in a disproportionate inhibition of synthesis of these hypothetical transcription factors. Transcription of a class of proliferation-related genes ceases as a result.

Animals↗
PubMed1989

Expression and DNA sequence of RED1, a gene required for meiosis I chromosome segregation in yeast.

Genetic studies have previously demonstrated that the RED1 gene of Saccharomyces cerevisiae is required for chromosome segregation at the first meiotic division. Northern blot hybridization analysis indicates that the RED1 gene produces two transcripts of 2.75 and 3.2 kilobases. The major 2.75 kb transcript is not present in mitotic cells and is meiotically induced to accumulate maximally just prior to the meiosis I division. The DNA sequence of the RED1 gene was determined and used to predict the amino acid sequence of the encoded gene product. The RED1 protein is 827 amino acids in length and has a molecular weight of 95.5 kilodaltons. There is no significant homology between the RED1 amino acid sequence and other known protein sequences, including those encoded by genes essential for meiosis.

Amino Acid Sequence↗
PubMed1989

Applying expert system techniques to human genetics.

Although expert systems have been developed in a variety of medical areas, there has been very little application of expert system techniques to the field of human genetics. The purpose of the research project described in this paper was (1) to experiment with different types of knowledge representation for data and knowledge structures in human genetics and (2) to explore the applicability of different inference mechanisms for various genetic problems. We present an object-oriented and a fact-based model for the representation of genealogical information and describe two prototype systems.

Algorithms↗
PubMed1989

Effect of verapamil on cell cycle transit and c-myc gene expression in normal and malignant murine cells.

Verapamil, the prototype calcium channel blocker, reversibly inhibits cell proliferation in many normal and tumour cell lines (Schmidt et al., Cancer Res., 48, 3617, 1988). We have found that two closely related cell lines - B16 murine melanoma cells and B10.BR normal murine melanocytes growing in culture - behave differently in the presence of verapamil, and we are now utilising these two related cell lines to help elucidate the molecular basis of verapamil's antiproliferative effect. In this study, we studied cell cycle phase distribution and c-myc gene expression in both cell lines in the absence of verapamil, during incubation with verapamil and after the cells were washed free of verapamil. Our studies show that 100 microM verapamil rapidly blocks DNA synthesis in melanocytes but not in B16 cells. Similarly, incubation with verapamil for 6-24 h results in a decreased c-myc signal in melanocytes, but a transient increase in c-myc expression in B16 cells. After verapamil is washed from the cells following a 24-h incubation with drug, c-myc expression increases in melanocytes as they begin again to proliferate, but decreases in B16 cells as they begin to die. Our disparate results with these cell lines suggest that c-myc gene expression, regardless of its known involvement in growth control, is not the immediate target for verapamil's inhibitory action.

Animals↗
PubMed1989

Recursive descent probabilities for rare recessive lethals.

Recursively computed descent probabilities provide an effective way to evaluate possible ancestries of rare alleles segregating in large and complex genealogies, but they ignore information other than the descent to a small set of current gene copies. We show how descent probability computations can be modified to incorporate the fact that no ancestor can be affected by a lethal recessive trait. This methodology is applied to two rare recessive traits segregating in a complex Hutterite (Lehrerleut) genealogy.

Alleles↗
PubMed1989

Productivity measurement for clinical nurse specialists.

The clinical nurse specialists (CNSs) at an 814-bed tertiary care center have collaborated to develop a method for measuring and evaluating productivity of the CNS role. This method, which uses the CIPP Evaluation Model as a framework, parallels the nursing process and is outcome oriented. The applicability of this method to other fixed positions may be of interest to nursing managers and administrators.

Efficiency↗
PubMed1988

Transient activation of c-myc protooncogene expression in Leydig cells by human chorionic gonadotropin.

This study evaluated the effects of in vivo administration of human chorionic gonadotropin (hCG) on c-myc oncogene expression in Leydig cells. Sprague-Dawley rats (46-50 days old) were treated with hCG (10 units, i.p.), and purified Leydig cells were isolated 1-24 h later. HCG caused a transient elevation of c-myc mRNA in 4 h and returned to normal or lower than normal levels at 24 h. There was no change in c-fos or beta-actin mRNA levels. Our results suggest that the growth promoting effects of hCG on Leydig cells may be mediated by the transient expression of c-myc protooncogene.

Actins↗
PubMed1988

Modification of human thrombin: effect on thrombomodulin binding.

Thrombomodulin, an endothelial cell protein, binds thrombin with high affinity and alters thrombin from a procoagulant to an anticoagulant molecule. In this study, chemical and/or proteolytic modification of thrombin was carried out to identify the essential components required for its interaction with thrombomodulin. Modification of thrombin at the catalytic site serine and histidine residues, with Diisopropylfluorophosphate and Tosyl-L-lysine chloromethyl ketone, resulted in loss of clotting and amidolytic activity. Both Diisopropyl phosphoryl-thrombin and Tosyl-L-chloromethyl ketone-thrombin inhibited native-thrombin: thrombomodulin catalyzed protein C activation with Ki values of 5 nM and 6 nM respectively indicating no loss of affinity for thrombomodulin. Oxidation of tryptophan residues with N-bromosuccinimide or iodination of tyrosine residues of thrombin led to reduced clotting and amidolytic activity as well as a reduced ability to interact with thrombomodulin. Modification of arginine residues with Phenylglyoxal and 2,3,Butanedione led to loss of thrombomodulin binding affinity. Limited proteolysis of thrombin by trypsin yielded the derivative beta-thrombin which had also lost its ability to interact with thrombomodulin. Deglycosylation of thrombin did not alter its binding affinity for thrombomodulin. These results indicate that one or more tryptophan, arginine and tyrosine residues are essential for the recognition of thrombin by thrombomodulin whilst the carbohydrate side chain and the active site residues of the thrombin molecule are not involved in thrombomodulin binding.

Bromosuccinimide↗
PubMed1988

Linkage information and bias in the presence of interference.

Although interference is an important biological phenomenon, linkage analyses often ignore it for computational efficiency. In this paper we examine the effects of ignoring interference on estimates of recombination fraction, and the power of statistical tests to detect interference. We show that for gametes from phase-known triple heterozygotes, no bias in the recombination fraction for adjacent loci results from the assumption of lack of interference even if interference is present. However, for samples from pairwise informative samples, there is bias introduced. An analytical form for this bias is obtained.

Chromosome Mapping↗
PubMed1988

Two-locus and three-locus gene identity by descent in pedigrees.

Although there have been several mathematical formulations of multilocus segregation, multilocus gene identity by descent in pedigrees has been little considered. Here we present a computationally feasible algorithm for the computation of two-locus kinship for individuals between whom there may be multiple complex relationships, and use it to investigate patterns of two-locus gene identity by descent for some standard relationships. We also present an explicit formula, which is used to discuss the determinants of two-locus identity and the relationship to three-locus identity by descent. With the current increasing density of information on individual genomes available from DNA polymorphisms, gene identity at linked loci has practical importance. Procedures for the estimation of relationships between individuals on the basis of genetic data will have increased flexibility to discriminate wider classes of genealogical relationship where information on multiple linked loci can be employed. Gene identity by descent at linked loci is also a key aspect of mapping rare recessive diseases from data on inbred individuals.

Chromosome Mapping↗
PubMed1988

Glucocorticoid regulation of the genes encoding thymidine kinase, thymidylate synthase, and ornithine decarboxylase in P1798 cells.

The expression of a number of genes was measured in P1798 cells treated for various periods of time with 0.1 microM dexamethasone. Thymidine kinase (TK) activity decreased under these conditions with 50% inhibition achieved within approximately 8 h. Decreased TK activity was associated with reduced abundance of TK mRNA. Analysis of nuclear transcription indicated that this was attributable to a decrease in the number of RNA polymerase II molecules engaged in transcription of the TK gene. With respect to TK, there was an overall correlation between enzyme activity, mRNA, and nuclear transcription. The data are consistent with the hypothesis that glucocorticoid inhibition of expression of TK is primarily due to inhibition of transcription. Transcription of the TK gene was also reduced by greater than 90% after inhibition of protein synthesis for 6 h. This suggests that transcription of this gene requires a protein of short biological half-life. It is proposed that this hypothetical transcription factor is regulated by glucocorticoids. The amount of thymidylate synthase and dihydrofolate reductase remained constant for at least 24 h in dexamethasone-treated P1798 cells. Dihydrofolate reductase mRNA likewise remained constant. However, the mRNA encoding thymidylate synthase decreased 80-90% within 24 h. The mRNA encoding ornithine decarboxylase also decreased. In neither case did this appear to be primarily due to inhibition of transcription of the respective genes. The abundance of the mRNAs encoding hypozanthine-guanine phosphoribosyl transferase and phosphoglycerate kinase did not decrease in dexamethasone-treated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗