Showing papers by "University of North Carolina at Chapel Hill published in 1993"

The proactive component of organizational behavior: A measure and correlates

Abstract: This study investigated a personal disposition toward proactive behavior, defined as the relatively stable tendency to effect environmental change. We developed an initial scale to assess the construct and administered it to a sample of 282 undergraduates. Factor analysis led to a revised, unidimensional scale with sound psychometric properties. A second sample of 130 undergraduate students was used to determine the relationships between the proactive scale and the ’Big Five‘ personality domains: neuroticism, extraversion, openness, agreeableness, and conscientiousness. In a third sample of 148 MBA students, we assessed the proactive scale's relationships with three personality traits and three criterion measures. Consistent with hypotheses, scores on the proactive scale correlated with need for achievement, need for dominance, and independent measures of the nature of subjects' extracurricular and civic activities, the nature of their major personal achievements, and peer nominations of transformational leaders. We discuss the potential of the proactive construct to enhance our understanding of, and ability to predict, a wide range of behaviors.

U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact.

Abstract: Our objective was to obtain national data of the estimated prevalence, sociodemographic relationships, and health impact of persons with functional gastrointestinal disorders. We surveyed a stratified probability random sample of U.S householders selected from a data base of a national market firm (National Family Opinion, Inc.). Questions were asked about bowel symptoms, sociodemographic associations, work absenteeism, and physician visits. The sampling frame was constructed to be demographically similar to the U.S. householder population based on geographic region, age of householder, population density, household income and household size. Of 8250 mailings, 5430 were returned suitable for analysis (66% response). The survey assessed the prevalence of 20 functional gastrointestinal syndromes based on fulfillment of multinational diagnostic (Rome) criteria. Additional variables studied included: demographic status, work absenteeism, health care use, employment status, family income, geographic area of residence, population density, and number of persons in household. For this sample, 69% reported having at least one of 20 functional gastrointestinal syndromes in the previous three months. The symptoms were attributed to four major anatomic regions: esophageal (42%), gastroduodenal (26%), bowel (44%), and anorectal (26%), with considerable overlap. Females reported greater frequencies of globus, functional dysphagia, irritable bowel syndrome, functional constipation, functional abdominal pain, functional biliary pain and dyschezia; males reported greater frequencies of aerophagia and functional bloating. Symptom reporting, except for incontinence, declines with age, and low income is associated with greater symptom reporting. The rate of work/school absenteeism and physician visits is increased for those having a functional gastrointestinal disorder. Furthermore, the greatest rates are associated with those having gross fecal incontinence and certain more painful functional gastrointestinal disorders such as chronic abdominal pain, biliary pain, functional dyspepsia and IBS. Preliminary information on the prevalence, socio-demographic features and health impact is provided for persons who fulfill diagnostic criteria for functional gastrointestinal disorders.

Quasilocal energy and conserved charges derived from the gravitational action

Abstract: The quasilocal energy of gravitational and matter fields in a spatially bounded region is obtained by employing a Hamilton-Jacobi analysis of the action functional. First, a surface stress-energy-momentum tensor is defined by the functional derivative of the action with respect to the three-metric on $^{3}$B, the history of the system's boundary. Energy surface density, momentum surface density, and spatial stress are defined by projecting the surface stress tensor normally and tangentially to a family of spacelike two-surfaces that foliate $^{3}$B. The integral of the energy surface density over such a two-surface B is the quasilocal energy associated with a spacelike three-surface \ensuremath{\Sigma} whose orthogonal intersection with $^{3}$B is the boundary B. The resulting expression for quasilocal energy is given in terms of the total mean curvature of the spatial boundary B as a surface embedded in \ensuremath{\Sigma}. The quasilocal energy is also the value of the Hamiltonian that generates unit magnitude proper-time translations on $^{3}$B in the timelike direction orthogonal to B. Conserved charges such as angular momentum are defined using the surface stress tensor and Killing vector fields on $^{3}$B. For spacetimes that are asymptotically flat in spacelike directions, the quasilocal energy and angular momentum defined here agree with the results of Arnowitt, Deser, and Misner in the limit that the boundary tends to spatial infinity. For spherically symmetric spacetimes, it is shown that the quasilocal energy has the correct Newtonian limit, and includes a negative contribution due to gravitational binding.

Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene

Abstract: Estrogen receptor and its ligand, estradiol, have long been thought to be essential for survival, fertility, and female sexual differentiation and development. Consistent with this proposed crucial role, no human estrogen receptor gene mutations are known, unlike the androgen receptor, where many loss of function mutations have been found. We have generated mutant mice lacking responsiveness to estradiol by disrupting the estrogen receptor gene by gene targeting. Both male and female animals survive to adulthood with normal gross external phenotypes. Females are infertile; males have a decreased fertility. Females have hypoplastic uteri and hyperemic ovaries with no detectable corpora lutea. In adult wild-type and heterozygous females, 3-day estradiol treatment at 40 micrograms/kg stimulates a 3- to 4-fold increase in uterine wet weight and alters vaginal cornification, but the uteri and vagina do not respond in the animals with the estrogen receptor gene disruption. Prenatal male and female reproductive tract development can therefore occur in the absence of estradiol receptor-mediated responsiveness.

A simultaneous evaluation of 10 commonly used physical activity questionnaires

Abstract: Ten commonly used physical activity questionnaires were evaluated for reliability and validity in 78 men and women aged 20–59, with varying physical activity habits. One month reliability was found to be high for all questionnaires except those pertaining only to the last week or month. Long

Signal transduction from the extracellular matrix.

Abstract: Adhesive interactions between cells and the insoluble meshwork of extracellular matrix proteins play a vital role in embryonic morphogenesis (33, 36, 94, 109, 135, 145), and in the regulation of gene expression in cells of the adult organism (1, 6, 105, 124). While the overall phenomenology ofextracellular matrix (ECM) 1 effects on cell differentiation is well known, the biochemical and molecular bases for these effects have remained elusive. It is clear that many of the interactions between cells and the ECM are mediated by the integrin family of cell surface receptors (2, 3, 13, 72). However, the precise mechanism(s) whereby signals from ECM proteins are transduced via integfins to the intraceUular machinery that controls cell growth, behavior, and differentiation, remains poorly defined. There are many compelling examples of control of cell differentiation and gene expression through adhesive interactions with extracellular matrix. In fibroblasts, cell attachment has been reported to rapidly increase expression of c-los and pro al(I) collagen messages (26, 27). Adhesion to fibronectin fragments, or cross-linking of the integfin oe5/~l fibronectin receptor with antibody, induced the expression of metalloprotease genes in fibroblastic cells; interestingly, intact fibronectin did not provoke this response nor did fibronectin fragments in solution (137). In a somewhat similar vein, stimulation of the C~v//~3 integrin in melanoma cells induced the expression of type IV collagenase and increased the invasive ability of these cells (115). The capacity of breast epithelial cells to express milk proteins in response to hormonal stimuli is quite dependent on the presence of an appropriate ECM (124). Studies in this system have led to the preliminary identification of matrix-dependent elements in the promoter region of the ~ casein gene (111). In the immune system, activation of T-lymphocytes through the T-cell antigen receptor is markedly enhanced by integrin-mediated adhesion to fibronectin or laminin (85, 97, 119). This process is part of a complex dialogue involving adhesive receptors occurring between mature T-cells and antigen presenting cells, as well as during lymphocyte differentiation (40, 132, 133). There is extensive signaling \"cross talk\" between

The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature.

Abstract: We provide here a list of 221 P450 genes and 12 putative pseudogenes that have been characterized as of December 14, 1992. These genes have been described in 31 eukaryotes (including 11 mammalian and 3 plant species) and 11 prokaryotes. Of 36 gene families so far described, 12 families exist in all mammals examined to date. These 12 families comprise 22 mammalian subfamilies, of which 17 and 15 have been mapped in the human and mouse genome, respectively. To date, each subfamily appears to represent a cluster of tightly linked genes. This revision supersedes the previous updates [Nebert et al., DNA 6, 1–11, 1987; Nebert et al., DNA 8, 1–13, 1989; Nebert et al., DNA Cell Biol. 10, 1–14 (1991)] in which a nomenclature system, based on divergent evolution of the superfamily, has been described. For the gene and cDNA, we recommend that the italicized root symbol "CYP" for human ("Cyp" for mouse), representing "cytochrome P450," be followed by an Arabic number denoting the family, a letter designating...

Rigor or rigor mortis: the problem of rigor in qualitative research revisited.

Abstract: Issues are raised by the persistent concern with achieving rigor in qualitative research, including the rigidity that often characterizes the search for validity in qualitative work and the threat to validity that the search for reliability may pose. Member validation is highlighted as a technique that exemplifies not only the practical, but also the profoundly theoretical, representational, and even moral problems raised by all procedures aimed at ensuring the trustworthiness of qualitative work.

Apoptosis: the biochemistry and molecular biology of programmed cell death.

Abstract: I. Introduction DEATH, along with growth and differentiation, is a critical part of the life cycle of a cell. Homeostatic control of cell number is thought to be the result of the dynamic balance between cell proliferation and cell death. It is only in the past few years, however, that attention has been focused on the physiological occurrence of cell death and its role in homeostasis. Researchers have become increasingly more aware during this time that this type of “natural” death, which is now called apoptosis or programmed cell death, is a widespread phenomenon that plays a crucial role in a myriad of physiological and pathological processes. This review first briefly covers some historical perspective on the discovery of apoptotic cell death, the characteristic morphology that accompanies this process, and the numerous cell types and mediators with which programmed cell death is associated. The bulk of the review discusses our current understanding of the biochemical and molecular mechanisms by which...

Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair

Abstract: The genomes of all eukaryotes contain tracts of DNA in which a single base or a small number of bases is repeated. Expansions of such tracts have been associated with several human disorders including the fragile X syndrome. In addition, simple repeats are unstable in certain forms of colorectal cancer, suggesting a defect in DNA replication or repair. We show here that mutations in any three yeast genes involved in DNA mismatch repair (PMS1, MLH1 and MSH2) lead to 100- to 700-fold increases in tract instability, whereas mutations that eliminate the proof-reading function of DNA polymerases have little effect. The meiotic stability of the tracts is similar to the mitotic stability. These results suggest that tract instability is associated with DNA polymerases slipping during replication, and that some types of colorectal cancer may reflect mutations in genes involved in DNA mismatch repair.

Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: a mechanism for NF-kappa B activation.

Abstract: Nuclear factor kappa B (NF-kappa B) is a critical regulator of several genes which are involved in immune and inflammation responses. NF-kappa B, consisting of a 50-kDa protein (p50) and a 65-kDa protein (p65), is bound to a cytoplasmic retention protein called I kappa B. Stimulation of cells with a variety of inducers, including cytokines such as tumor necrosis factor and interleukin-1, leads to the activation and the translocation of p50/65 NF-kappa B into the nucleus. However, the in vivo mechanism of the activation process remains unknown. Here, we provide the first evidence that the in vivo mechanism of NF-kappa B activation is through the phosphorylation and subsequent loss of its inhibitor, I kappa B alpha. We also show that both I kappa B alpha loss and NF-kappa B activation are inhibited in the presence of antioxidants, demonstrating that the loss of I kappa B alpha is a prerequisite for NF-kappa B activation. Finally, we demonstrate that I kappa B alpha is rapidly resynthesized after loss, indicating that an autoregulatory mechanism is involved in the regulation of NF-kappa B function. We propose a mechanism for the activation of NF-kappa B through the modification and loss of I kappa B alpha, thereby establishing its role as a mediator of NF-kappa B activation.

The Evolution of Agenda-Setting Research: Twenty-Five Years in the Marketplace of Ideas

Abstract: Communication scholars frequently invoke the concept of a marketplace of ideas during discussions about speechmaking, the diversity of media content and voices, and related First Amendment issues. They invoke it less often during intramural discussions of how specific concepts and perspectives, or our research agendas as a whole, have evolved over the years. Yet communication research does operate in a marketplace of ideas that is the quintessential laissez-faire market. The role of our journals is to create a market for the ideas advanced by members of the field. Individual scholars pick and choose topics at will-idiosyncratically and whimsically, some critics say-and publish at irregular intervals. Research teams, to the extent that they exist in communication research, usually arise spontaneously and have short life spans. Institutionalized focused research programs are rare. The communication research marketplace is a volatile arena, a situation fostered by the rapidly changing nature of communication itself during the past 50 years. Under these circumstances the continuing and growing vitality of agenda-setting research is remarkable. As a theoretical perspective, it has had a rich 25-year history since McCombs and Shaw’s (1972) opening gambit during the 1968 presidential elect ion. Philosopher of science James Conant (1951) noted that the hallmark o f a successful theory is its fruitfulness in continually generating new questions and identifying new avenues of scholarly inquiry. The fruitfulness of the agenda-setting metaphor is documented by three features: (a) the steady historical growth of its literature, (b> its ability to integrate a number of communication research subfields under a single theoretical um-

Association of Hormone-Replacement Therapy with Various Cardiovascular Risk Factors in Postmenopausal Women

Abstract: Background Most epidemiologic studies of cardiovascular disease in postmenopausal women suggest that estrogen-replacement therapy has a protective effect. The effects of the use of estrogen combined with progestin are less well studied. Methods To examine the associations of hormone-replacement therapy with concentrations of plasma lipids and hemostatic factors, fasting serum concentrations of glucose and insulin, and blood pressure, we studied 4958 postmenopausal women participating in a population-based investigation. Using cross-sectional data, we classified the women into four groups according to their use of hormone-replacement therapy: current users of estrogen alone, current users of estrogen with progestin, nonusers who had formerly used these hormones, and nonusers who had never used them. Results Current users had higher mean levels of high-density lipoprotein cholesterol, its subfractions high-density lipoprotein2 and high-density lipoprotein3, and apolipoprotein A-I than nonusers, and lower me...

Prediction of mortality and morbidity with a 6-minute walk test in patients with left ventricular dysfunction. SOLVD Investigators

Abstract: Objective. —To study the potential usefulness of the 6-minute walk test, a self-paced submaximal exercise test, as a prognostic indicator in patients with left ventricular dysfunction. Design. —Data were collected during a prospective cohort study, the Studies of Left Ventricular Dysfunction (SOLVD) Registry Substudy. Setting. —Twenty tertiary care hospitals in the United States, Canada, and Belgium. Participants. —A stratified random sample of 898 patients from the SOLVD Registry who had either radiological evidence of congestive heart failure and/or an ejection fraction of 0.45 or less were enrolled in the substudy and underwent a detailed clinical evaluation including a 6-minute walk test. Patients were followed up for a mean of 242 days. Outcome Measures. —Mortality and hospitalization. Results. —During follow-up, 52 walk-test participants (6.2%) died and 252 (30.3%) were hospitalized. Hospitalization for congestive heart failure occurred in 78 participants (9.4%), and the combined endpoint of death or hospitalization for congestive heart failure occurred in 114 walk-test participants (13.7%). Compared with the highest performance level, patients in the lowest performance level had a significantly greater chance of dying (10.23% vs 2.99%;P=.01), of being hospitalized (40.91% vs 19.90%;P=.002), and of being hospitalized for heart failure (22.16% vs 1.99%;P Conclusion. —The 6-minute walk test is a safe and simple clinical tool that strongly and independently predicts morbidity and mortality in patients with left ventricular dysfunction. (JAMA. 1993;270:1702-1707)

Severity of spatial learning impairment in aging: Development of a learning index for performance in the Morris water maze.

Abstract: The Morris water maze task was originally designed to assess the rat's ability to learn to navigate to a specific location in a relatively large spatial environment. This article describes new measures that provide information about the spatial distribution of the rat's search during both training and probe trial performance. The basic new measure optimizes the use of computer tracking to identify the rat's position with respect to the target location. This proximity measure was found to be highly sensitive to age-related impairment in an assessment of young and aged male Long-Evans rats. Also described is the development of a learning index that provides a continuous, graded measure of the severity of age-related impairment in the task. An index of this type should be useful in correlational analyses with other neurobiological or behavioral measures for the study of individual differences in functional/biological decline in aging.

Commitment Processes in Close Relationships: An Interdependence Analysis

Abstract: This article employs interdependence theory as a means of understanding how and why some relationships survive difficult times whereas other promising relationships end. Interdependence theory makes important distinctions between satisfaction and dependence. These distinctions are extended in the investment model, a theory of the process by which individuals become dependent on and committed to their relationships. The investment model suggests that dependence increases not only as a consequence of increasing satisfaction, but also because available alternatives are perceived to be poor and numerous important resources are invested in a relationship. Subjective commitment summarizes the nature of an individual's dependence on a partner, and represents broad, long-term orientation toward a relationship. Strong commitment not only makes individuals more likely to remain with their partners, but also promotes a variety of relationship maintenance behaviors such as adaptive social comparison and perceived rel...

Introduction to SH Lie algebras for physicists

Abstract: UNC-MATH-92/2originally April 27, 1990, revised September 24, 1992INTRODUCTION TO SH LIE ALGEBRAS FOR PHYSICISTSTom LadaJim StasheffMuch of point particle physics can be described in terms of Lie algebras andtheir representations. Closed string field theory, on the other hand, leads to ageneralization of Lie algebra which arose naturally within mathematics in the studyof deformations of algebraic structures [SS]. It also appeared in work on higherspin particles [BBvD]. Representation theoretic analogs arose in the mathematicalanalysis of the Batalin-Fradkin-Vilkovisky approach to constrained Hamiltonians[S6].The sh Lie algebra of closed string field theory [SZ], [KKS], [K], [Wies], [WZ],[Z] is defined on the full Fock complex of the theory, with the BRST differential Q.Following Zwiebach [Z], we stipulate that the string fields B

Report of the International Workshop on Screening for Breast Cancer

Abstract: Background Over the past 30 years, eight major randomized controlled trials of breast cancer screening--with mammography and/or clinical breast examination--have been conducted. Results from several trials have been updated during the past year, and initial results of three other trials have been reported. Purpose The National Cancer Institute held an International Workshop on Screening for Breast Cancer in February 1993 to conduct a thorough and objective critical review of the world's most recent clinical trial data on breast cancer screening, consider the new evidence, assess the current state of knowledge, and identify issues needing further research. Methods Investigators representing the eight randomized controlled trials of breast cancer screening in women aged 40-74 presented published and unpublished data. Evidence relating to the effectiveness of breast cancer screening in different age groups, especially women aged 40-49, was presented. Results For women aged 40-49, randomized controlled trials consistently demonstrated no benefit from screening in the first 5-7 years after study entry. A meta-analysis of six trials found a relative risk of 1.08 (95% confidence interval = 0.85-1.39) after 7 years' follow-up. After 10-12 years of follow-up, none of four trials have found a statistically significant benefit in mortality; a combined analysis of Swedish studies showed a statistically insignificant 13% decrease in mortality at 12 years. Only one trial (Health Insurance Plan) has data beyond 12 years of follow-up, and results show a 25% decrease in mortality at 10-18 years. Statistical significance of this result is disputed, however. In women aged 50-69, all studies show mortality reductions; three of four studies show reductions of about 30% at 10-12 years after study entry. Results from two of these trials were statistically significant. Too few women over age 70 have been included in studies for adequate analysis. Conclusions For women aged 40-49, randomized controlled trials of breast cancer screening show no benefit 5-7 years after entry. At 10-12 years, benefit is uncertain and, if present, marginal; thereafter, it is unknown. For women aged 50-69, screening reduces breast cancer mortality by about a third. Currently available data for women age 70 or older are inadequate to judge the effectiveness of screening. Implications Randomized trials have provided stronger scientific evidence regarding the effectiveness of screening for breast cancer than for any other cancer. However, much still needs to be learned. Periodic gatherings of scientists in the field should speed the process.

Genetic Risk and Carcinogen Exposure: a Common Inherited Defect of the Carcinogen-Metabolism Gene Glutathione S-Transferase M1 (GSTM1) That Increases Susceptibility to Bladder Cancer

Abstract: Background Numerous studies have associated bladder cancer with exposure to carcinogens present in tobacco smoke and other environmental or occupational exposures. Approximately 50% of all humans inherit two deleted copies of the GSTM1 gene which encodes for the carcinogen-detoxification enzyme glutathione S-transferase M1. Recent findings suggest that the GSTM1 gene may modulate the internal dose of environmental carcinogens and thereby affect the risk of developing bladder cancer. Purpose We investigated whether the absence of the GSTM1 gene affects bladder cancer risk and whether there are racial differences in GSTM1 genotype frequency. Methods Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the homozygous deleted genotype (GSTM1 0/0) in 229 patients with transitional cell carcinoma of the bladder and 211 control subjects who were enrolled from the Urology Clinics at Duke University Medical Center and the University of North Carolina Hospitals. Control subjects were urology clinic patients who primarily presented with benign prostatic hypertrophy or impotence, who had no history of any cancer other than nonmelanoma skin cancer, and who were frequency matched to case patients on race, sex, and age (10-year age intervals). In order to explore racial differences in GSTM1 gene frequency, genotype was also determined in a community-based sample of 466 paid, healthy, unrelated volunteers from Durham and Chapel Hill, N.C. The presence or absence of the GSTM1 gene locus was determined by using a differential PCR, a semiquantitative technique in which multiple genes are coamplified. Results Overall, the GSTM1 0/0 genotype conferred a 70% increased risk of bladder cancer (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.2-2.5; P = .004). Absence of the GSTM1 gene encoding the glutathione S-transferase M1 enzyme significantly increased risk to persons with exposure to the carcinogens in tobacco smoke (OR = 1.8; 95% CI = 1.2-3.0; P = .01) but poses little increased risk to persons without such exposure. Persons with smoking exposure of more than 50 pack-years who had the GSTM1 0/0 genotype had a sixfold greater risk relative to persons in the lowest risk group (i.e., nonsmokers who were GSTM1 +/+ or +/0). In the pooled clinic control and community sample groups (677 individuals), the GSTM1 0/0 genotype occurred less frequently among Blacks (35%) than among Whites (49%, P Conclusions These findings support a protective role for the GSTM1 gene in bladder cancer. From these findings, it is estimated that 25% of all bladder cancer may be attributable to the at-risk GSTM1 0/0 genotype.

The insulin-like growth factors.

Abstract: The recent availability of reagents to study the IGFs, their receptors, and binding proteins has led to an explosive growth in the study of IGF physiology. However, most studies to date have been descriptive, and studies delineating mechanisms of action are limited. It is apparent that most organ systems synthesize several components of the IGF system necessary for IGF to function in an autocrine or paracrine fashion and that regulation of this system occurs at the local level. However, the relative importance of locally produced IGF vs circulating IGF remains unclear. The mechanisms by which the IGFBPs modulate IGF activity are crucial to understanding this system, and identification of specific roles for each of these proteins will be required. Of critical importance is the identity of the intracellular signal transduction system by which the IGF receptor mediates the effects of the IGFs, and the delineation of mechanisms by which the IGFBPs interact with the receptor at the cellular level. It is also of interest to determine what role, if any, the IGF-II receptor plays in mediating the growth-promoting effects of the IGFs. The ubiquitous distribution of the IGFs, IGFBPs, and IGF receptors indicates that they may play a role in the regulation of coordinate growth among several tissues and cell types. Understanding the mechanisms by which these components interact to coordinate growth responses between different cell types should greatly enhance our understanding of normal growth and development.

Assessment, enhancement, and verification determinants of the self-evaluation process.

Abstract: The 3 major self-evaluation motives were compared: self-assessment (people pursue accurate self-knowledge), self-enhancement (people pursue favorable self-knowledge), and self-verification (people pursue highly certain self-knowledge). Ss considered the possession of personality traits that were either positive or negative and either central or peripheral by asking themselves questions that varied in diagnosticity (the extent to which the questions could discriminate between a trait and its alternative) and in confirmation value (the extent to which the questions confirmed possession of a trait)

Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors.

Abstract: Background. Although digoxin is effective in the treatment of patients with chronic heart failure who are receiving diuretic agents, it is not clear whether the drug has a role when patients are receiving angiotensin-converting-enzyme inhibitors, as is often the case in current practice. Methods. We studied 178 patients with New York Heart Association class II or III heart failure and left ventricular ejection fractions of 35 percent or less in normal sinus rhythm who were clinically stable while receiving digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor (captopril or enalapril). The patients were randomly assigned in a double-blind fashion either to continue receiving digoxin (85 patients) or to be switched to placebo (93 patients) for 12 weeks

Molecular mechanism of transcription-repair coupling

Abstract: Lesions in the transcribed strand block transcription and are repaired more rapidly than lesions in the nontranscribed (coding) strand which do not block RNA polymerase (RNAP). It has been shown previously that in Escherichia coli the mfd (mutation frequency decline) gene is necessary for strand-specific repair. The mfd gene was cloned and sequenced and the Mfd protein was purified and used to reconstitute strand-specific repair in a completely defined system. The mfd gene encodes a protein of 130 kilodaltons and contains the so-called "helicase motifs," a leucine zipper motif, and regions of sequence similarity to UvrB and RecG proteins. The Mfd protein was shown to (i) displace RNAP stalled at a lesion in an adenosine triphosphate-dependent reaction, (ii) bind to the damage recognition subunit (UvrA) of the excision nuclease, and (iii) stimulate the repair of the transcribed strand only when transcription is taking place. Thus, Mfd appears to target the transcribed strand for repair by recognizing a stalled RNAP and actively recruiting the repair enzyme to the transcription blocking lesion as it dissociates the stalled RNAP.

Cross-coupling of the NF-kappa B p65 and Fos/Jun transcription factors produces potentiated biological function.

Abstract: NF-kappa B and AP-1 represent distinct mammalian transcription factors that target unique DNA enhancer elements. The heterodimeric NF-kappa B complex is typically composed of two DNA binding subunits, NF-kappa B p50 and NF-kappa B p65, which share structural homology with the c-rel proto-oncogene product. Similarly, the AP-1 transcription factor complex is comprised of dimers of the c-fos and c-jun proto-oncogene products or of closely related proteins. We now demonstrate that the bZIP regions of c-Fos and c-Jun are capable of physically interacting with NF-kappa B p65 through the Rel homology domain. This complex of NF-kappa B p65 and Jun or Fos exhibits enhanced DNA binding and biological function via both the kappa B and AP-1 response elements including synergistic activation of the 5' long terminal repeat of the human immunodeficiency virus type 1. These findings support a combinatorial mechanism of gene regulation involving the unexpected cross-coupling of two different classes of transcription factors to form novel protein complexes exhibiting potentiated biological activity.