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Biomedical subjects

C J Williams

Publications and source records attributed to C J Williams.

At least 19 recordsLinked to original sources
PubMed1992

Long-term bone loss in men: effects of genetic and environmental factors.

OBJECTIVE: To identify environmental factors associated with bone loss in adult male twins and to determine the extent to which shared environmental characteristics affect estimates of the genetic influence on bone loss. DESIGN: A 16-year cohort study. SETTING: A midwestern university hospital. PARTICIPANTS: One hundred and eleven male veterans of World War II or the Korean conflict, born between 1916 and 1927. All were twins, with the sample comprising 48 pairs and 15 persons whose twin brothers were deceased or seriously ill. MEASUREMENTS: Bone mass and environmental characteristics (cigarette smoking, alcohol consumption, physical activity, dietary calcium intake, use of thiazide diuretics) measured at baseline and 16 years later. RESULTS: Rates of radial bone loss averaged 0.45% per year. Those who both smoked and used alcohol at levels greater than the median for the population had a rate of bone loss (10% in 16 years) twice the rate of those who were below the median level for both variables (5% bone loss, P = 0.003). Rates of bone loss were correlated within twin pairs, and these correlations were diminished 25% to 35% by adjustments for environmental influences on bone loss. However, statistically significant within-pair correlations remained (r = 0.4), which did not differ between monozygotic and dizygotic twin pairs after adjustments for smoking, alcohol use, dietary calcium intake, and exercise. CONCLUSIONS: Bone loss in men during mid-life is determined, at least in part, by environmental factors, including smoking, alcohol intake, and, possibly, physical activity. Rates of bone loss were similar within twin pairs, apparently because of a shared environment.

Alcohol Drinking↗
PubMed1992

Quantitative dot blot analyses of blood-group-related antigens in paired normal and malignant human breast tissues.

Membranes were prepared from 31 breast-cancer specimens and adjacent mammary tissues, dot-blotted to nitrocellulose paper, and reacted with monoclonal antibodies (MAbs) (A, B, Lewis a, Lewis b, sialylated Lewis a, Lewis x, and Lewis y) and lectins (Ulex europaeus, peanut agglutinin) having various blood-group specificities. The expression of epithelial membrane antigen was assayed with MAb MA5. The ratio of breast-cancer to normal mammary membrane preparations (C/N ratios) of these reagents was measured by densitometric scanning. We observed a decrease in the levels of A, B, Lewis a, Lewis b, sialylated Lewis a, and Lewis y antigens and an increase of Lewis x, T, and MA5-reactive determinants in breast cancers. The incidence of incompatible A, as well as A and B, antigens was demonstrated for 2 patients of blood group B and O respectively. When the receptor content was plotted against the C/N ratio of these various reagents, a significant inverse relationship between the C/N ratio of Lewis x antigen and estrogen (ER) and progesterone receptor (PR) content was observed in breast cancers. The mean C/N ratio of Lewis x antigen was significantly higher in the ER-negative/PR-negative (ER-/PR-; 2.33 +/- 1.17), as compared with the ER-positive/PR-positive (ER+/PR+; 0.97 +/- 0.80). According to these observations, Lewis x antigen expression may be influenced by hormonal stimuli such as estrogen and progesterone.

ABO Blood-Group System↗
PubMed1992

Detection of sequence variants in the gene for human type II procollagen (COL2A1) by direct sequencing of polymerase chain reaction-amplified genomic DNA.

The direct sequencing of the human type II procollagen (COL2A1) gene from polymerase chain reaction (PCR)-amplified genomic DNA is described. Thirty-two regions of the COL2A1 gene were asymmetrically amplified with intron primers which were specifically chosen to amplify a region spanning 500 to 800 bp of sequence encoding one or more exons and their accompanying intervening sequences. Primers for dideoxynucleotide sequencing of the PCR products were then designed to provide complete exon sequence information and to insure that intron:exon splice junction sequence data would be obtained. Amplification and sequencing reactions were performed on an automated workstation to facilitate the handling of multiple DNA templates. The procedure allowed efficient sequencing of over 25,000 bp of each allele of the COL2A1 gene per diploid genome. We used this method for the comparative analyses of COL2A1 sequences in DNA isolated from the blood of 42 unrelated individuals and we identified 21 neutral sequence variants in the gene. The sequence variations were confirmed by independent assays, including restriction enzyme digestion. The sequence variants described here will be important for identifying haplotypes of the type II procollagen gene that will be useful in defining a genetic etiology for diseases of cartilaginous tissues.

Alleles↗
PubMed1992

Likelihood-based analyses of longitudinal twin and family data: experiences with pedigree-based approaches.

Substantial progress has been made recently in analyses of longitudinal twin and family data, principally for two reasons. The first is the continuing development of more refined models for describing longitudinal data; the second is the widespread availability of analytic methods (e.g. LISREL) with which to implement these models. Computational restrictions have limited likelihood-based analyses of longitudinal genetic data to analyses of covariance matrices or mean squares; however, advances in computer technology now make it feasible to conduct likelihood analyses of longitudinal pedigree data. We consider potential advantages of using pedigree-based methods. Our initial experiences with the application of these methods to simulated twin data, using the FISHER (Lange, K.L., et al., Genet. Epidemiol. 5:471, 1988) quantitative genetics package, are discussed, with particular attention to practical details such as running times on several computers. Preliminary results of the pedigree-based analyses, including robust estimation methods, convincingly demonstrate the failure of methods assuming the multivariate normal distribution for simulated twin data provided by Carey (this issue).

Adolescent↗
PubMed1992

Epithelial membrane antigen expression in breast fluids and 'witch's milk'.

We have examined breast fluids from non-lactating women and male neonates for the expression of epithelial membrane antigen (EMA), also termed polymorphic epithelial mucin (PEM). All fluids exhibited significant amounts of EMA as demonstrated by immunoblot analyses and enzyme immunoassay. EMA was present in the breast fluids of both pre- and post-menopausal women, and these results suggest that nipple aspirates could provide an easily accessible source of antigen for assessing the value of EMA as a tumor marker both before and after various therapeutic modalities. The presence of EMA in the 'witch's milks' indicates that full maturation of the breast is not a prerequisite for antigen expression in breast tissue.

Adult↗
PubMed1992

Plots for examination of univariate twin data.

We discuss informative plots for univariate twin data that can be used in conjunction with twin data analyses. The plots are useful for spotting outliers, spotting possible single gene effects, and displaying the contribution of individual twin pairs to the fit of genetic models of the data. We illustrate the use of the plots on bone mineral data, and present programs for generating the plots in SAS.

Data Interpretation, Statistical↗
PubMed1992

Role of G proteins in mouse egg activation: stimulatory effects of acetylcholine on the ZP2 to ZP2f conversion and pronuclear formation in eggs expressing a functional m1 muscarinic receptor.

Sperm-mediated egg activation may be analogous to ligand-mediated signal transduction through G protein-coupled receptors. We investigated this possibility in the mouse egg by microinjecting mouse oocytes with an m1 muscarinic receptor mRNA. Following oocyte maturation in vitro, the metaphase II-arrested eggs were treated with acetylcholine and its effect was examined on zona pellucida modifications and pronuclear formation, which are end points of early and late egg activation, respectively. Treatment of these eggs with acetylcholine reveals that both the ZP2 to ZP2f conversion and pronuclear formation occur. Atropine and microinjected GDP beta S block the acetylcholine-induced ZP2 conversion, suggesting that the acetylcholine effects are mediated via a functional G protein-coupled m1 receptor. The acetylcholine-induced ZP2 conversion, however, is not inhibited by pertussis toxin under conditions in which greater than 90% of the endogenous Gi is inactivated by ADP ribosylation. The presence of a pertussis toxin-insensitive G protein, Gq, is detected by immunoblotting; this G protein could be a candidate to mediate the pertussis toxin-insensitive effects of acetylcholine. Results of these experiments are consistent with the hypothesis that receptor-mediated G protein activation may play a role in egg activation.

Acetylcholine↗
PubMed1992

TWINAN90: a FORTRAN program for conducting ANOVA-based and likelihood-based analyses of twin data.

We discuss the program, TWINAN90, which can perform several different types of analysis of twin data. TWINAN90 incorporates the ANOVA-based twin analyses from the TWINAN twin analysis program, and also includes maximum likelihood estimation of parameters from three path models. Another feature of TWINAN90 is the optional output of a pedigree file which can be read by the quantitative genetics package FISHER. The diagnostic features of the program make TWINAN90 useful also for preliminary analyses prior to the use of more sophisticated modeling procedures which are available in packages such as LISREL and FISHER. An annotated printout from TWINAN90 is presented to illustrate the statistical analyses performed in the program.

Analysis of Variance↗
PubMed1992

Prevalence and prognostic significance of anticardiolipin antibodies in pregnancies complicated by human immunodeficiency virus-1 infection.

OBJECTIVES: Anticardiolipin antibodies are estimated to occur in 2.2% of all pregnancies and are associated with adverse outcomes including thrombotic events, fetal wastage, intrauterine growth retardation, and preterm delivery. We studied 32 human immunodeficiency virus-seropositive gravidas (1) to determine the prevalence of anticardiolipin antibodies in pregnant women infected with human immunodeficiency virus-1 and (2) to investigate the association between the presence of anticardiolipin antibodies and pregnancy outcome, disease status, and perinatal transmission of human immunodeficiency virus-1. STUDY DESIGN: Serum samples obtained at the first prenatal visit were analyzed for anticardiolipin immunoglobulin M and immunoglobulin G by enzyme-linked immunosorbent assay. Relevant antepartum, intrapartum, and postpartum data, including maternal CD4+ lymphocyte subsets, human immunodeficiency virus p24 antigen determinations, Venereal Disease Research Laboratory test, hematocrit, platelet counts, and placental pathologic tissue of the anticardiolipin antibody-positive and anticardiolipin antibody-negative groups were compared. RESULTS: Test results for 17 (53%) of patients were positive for anticardiolipin antibody: 4 had only immunoglobulin M, 1 had only immunoglobulin G, and the remaining 12 had both antibodies. The patients in the anticardiolipin antibody-positive group were delivered of infants with a mean gestational age of 39 weeks and mean birth weight of 2983 gm. In the anticardiolipin antibody-negative group 15 deliveries had a mean gestational age of 36.3 weeks and a mean birth weight of 2330 gm. CONCLUSIONS: We conclude that there is a high prevalence of anticardiolipin antibodies in patients who have human immunodeficiency virus, which is not associated with adverse maternal or neonatal outcome, maternal human immunodeficiency virus status, or perinatal transmission of human immunodeficiency virus-1.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Meta-analysis of the role of platinum compounds in advanced ovarian carcinoma. The Advanced Ovarian Cancer Trialists Group.

This paper presents a systematic overview or meta-analysis of 54 randomized clinical trials testing a variety of chemotherapeutic approaches in advanced ovarian carcinoma. Prolonged follow-up data are available for most patients and individual patient data were made available for all patients; analysis was made on the basis of "intention to treat." Our report concentrates on two comparisons: (1) platinum alone versus platinum in combination, which appears to show a long-term survival advantage for the combination (however, the platinum dose in the single-agent arm was relatively low); and (2) carboplatin versus cisplatin, which shows no obvious survival differences. It is striking that no single study to date has been large enough to detect the modest survival differences expected from current therapy. Consequently, a series of international studies have been initiated. The International Collaborative Ovarian Neoplasm (ICON) group will examine the role of adjuvant chemotherapy in early ovarian cancer (ICON 1) and will compare carboplatin with cisplatin, doxorubicin, and cyclophosphamide in more advanced disease (ICON 2).

Antineoplastic Combined Chemotherapy Protocols↗