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Showing papers by "Vanderbilt University published in 1994"


Journal ArticleDOI
TL;DR: The acute respiratory distress syndrome (ARDS), a process of nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, carries a high morbidity, mortality, and financial cost.
Abstract: The acute respiratory distress syndrome (ARDS), a process of nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, carries a high morbidity, mortality (10 to 90%), and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged, and it may be different in Europe. Part of the reason for these uncertainties are the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those who wish to know the true incidence and outcome of this clinical syndrome are stymied. The American-European Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important in order to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS.

6,233 citations


Journal ArticleDOI
TL;DR: In this paper, the authors presented a behavior versus outcome sales control continuum based on methods of monitoring, directing, evaluating, and compensating the salesperson, based on a behavioral model.
Abstract: In a previous volume of this journal, the authors presented a behavior versus outcome sales control continuum based on methods of monitoring, directing, evaluating, and compensating the salesperson...

1,663 citations


Journal ArticleDOI
22 Dec 1994-Nature
TL;DR: It is shown that adhesion of murine NIH3T3 fibroblasts to fibronectin promotes SH2-domain-mediated association of the GRB2 adaptor protein and the c-Src protein-tyrosine kinase (PTK) with FAK in vivo, and also results in activation of mitogen-activated protein Kinase (MAPK).
Abstract: THE cytoplasmic focal adhesion protein-tyrosine kinase (FAK) localizes with surface integrin receptors at sites where cells attach to the extracellular matrix. Increased FAK tyrosine phosphory-lation occurs upon integrin engagement with fibronectin. Here we show that adhesion of murine NIH3T3 fibroblasts to fibronectin promotes SH2-domain-mediated association of the GRB2 adaptor protein and the c-Src protein-tyrosine kinase (PTK) with FAK in vivo, and also results in activation of mitogen-activated protein kinase (MAPK). In v-Src-transformed NIH3T3, the association of v-Src, GRB2 and Sos with FAK is independent of cell adhesion to fibronectin. The GRB2 SH2 domain binds directly to tyrosine-phosphorylated FAK. Mutation of tyrosine residue 925 of FAK (YENV motif) to phenylalanine blocks GRB2 SH2-domain binding to FAK in vitro . Our results show that fibronectin binding to integrins on NIH3T3 fibroblasts promotes c-Src and FAK asso-ciation and formation of an integrin-activated signalling complex. Phosphorylation of FAK at Tyr 925 upon fibronectin stimulation creates an SH2-binding site for GRB2 which may link integrin engagement to the activation of the Ras/MAPK signal transduc-tion pathway.

1,582 citations


Journal ArticleDOI
04 Nov 1994-Science
TL;DR: It is established that defects in apoptosis, here caused by the inactivation of p53, can produce treatment-resistant tumors and suggested that p53 status may be an important determinant of tumor response to therapy.
Abstract: The therapeutic responsiveness of genetically defined tumors expressing or devoid of the p53 tumor suppressor gene was compared in immunocompromised mice. Tumors expressing the p53 gene contained a high proportion of apoptotic cells and typically regressed after treatment with gamma radiation or adriamycin. In contrast, p53-deficient tumors treated with the same regimens continued to enlarge and contained few apoptotic cells. Acquired mutations in p53 were associated with both treatment resistance and relapse in p53-expressing tumors. These results establish that defects in apoptosis, here caused by the inactivation of p53, can produce treatment-resistant tumors and suggest that p53 status may be an important determinant of tumor response to therapy.

1,582 citations


Journal ArticleDOI
06 Jul 1994-JAMA
TL;DR: It is concluded that ulcer patients with H. pylori infection require treatment with antimicrobial agents in addition to antisecretory drugs whether on first presentation with the illness or on recurrence.
Abstract: The National Institutes of Health Consensus Development Conference onHelicobacter pyloriin Peptic Ulcer Disease brought together specialists in gastroenterology, surgery, infectious diseases, epidemiology, and pathology, as well as the public to address the following questions: (1) What is the causal relationship ofH pylorito upper gastrointestinal disease? (2) How does one diagnose and eradicateH pyloriinfection? (3) Does eradication ofH pyloriinfection benefit the patient with peptic ulcer disease? (4) What is the relationship betweenH pyloriinfection and gastric malignancy? (5) WhichH pylori—infected patients should be treated? (6) What are the most important questions that must be addressed by future research inH pyloriinfections? Following 1½ days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the consensus panel concluded that (1) ulcer patients withH pyloriinfection require treatment with antimicrobial agents in addition to antisecretory drugs whether on first presentation with the illness or on recurrence; (2) the value of treating of nonulcerative dyspepsia patients withH pyloriinfection remains to be determined; and (3) the interesting relationship betweenH pyloriinfection and gastric cancers requires further exploration. (JAMA. 1994;272:65-69)

1,436 citations


Journal ArticleDOI
TL;DR: The results indicate that, compared to a manual method, the use of the semiautomatic technique not only facilitates the analysis of the images, but also has similar or lower intra- and interrater variabilities.
Abstract: The analysis of MR images is evolving from qualitative to quantitative. More and more, the question asked by clinicians is how much and where, rather than a simple statement on the presence or absence of abnormalities. The authors present a study in which the results obtained with a semiautomatic, multispectral segmentation technique are quantitatively compared to manually delineated regions. The core of the semiautomatic image analysis system is a supervised artificial neural network classifier augmented with dedicated preand postprocessing algorithms, including anisotropic noise filtering and a surface-fitting method for the correction of spatial intensity variations. The study was focused on the quantitation of white matter lesions in the human brain. A total of 36 images from six brain volumes was analyzed twice by each of two operators, under supervision of a neuroradiologist. Both the intra- and interrater variability of the methods were studied in terms of the average tissue area detected per slice, the correlation coefficients between area measurements, and a measure of similarity derived from the kappa statistic. The results indicate that, compared to a manual method, the use of the semiautomatic technique not only facilitates the analysis of the images, but also has similar or lower intra- and interrater variabilities. >

1,287 citations


Journal ArticleDOI
TL;DR: It is suggested that part of the effect of socioeconomic status on children's aggressive development may be mediated by status-related socializing experiences.
Abstract: The goal was to examine processes in socialization that might account for an observed relation between early socioeconomic status and later child behavior problems. A representative sample of 585 children (n = 51 from the lowest socioeconomic class) was followed from preschool to grade 3. Socioeconomic status assessed in preschool significantly predicted teacher-rated externalizing problems and peer-rated aggressive behavior in kindergarten and grades 1, 2, and 3. Socioeconomic status was significantly negatively correlated with 8 factors in the child's socialization and social context, including harsh discipline, lack of maternal warmth, exposure to aggressive adult models, maternal aggressive values, family life stressors, mother's lack of social support, peer group instability, and lack of cognitive stimulation. These factors, in turn, significantly predicted teacher-rated externalizing problems and peer-nominated aggression and accounted for over half of the total effect of socioeconomic status on these outcomes. These findings suggest that part of the effect of socioeconomic status on children's aggressive development may be mediated by status-related socializing experiences.

1,103 citations


Journal ArticleDOI
TL;DR: The intrarenal distribution of COX-2 and its increased expression in response to sodium restriction suggest that in addition to its proposed role in inflammatory and growth responses, this enzyme may play an important role in the regulation of salt, volume, and blood pressure homeostasis.
Abstract: The kidney is a rich source of prostaglandins. These eicosanoids, formed by cyclooxygenase-dependent metabolism of arachidonic acid, are important physiologic mediators of renal glomerular hemodynamics and tubular sodium and water reabsorption. Two separate isoforms of cyclooxygenase (COX) have now been identified: constitutive COX-1, encoded by a 2.8-kb mRNA, and mitogen-activated COX-2, encoded by a 4.0-4.5-kb mRNA. COX-2 expression increases during development and inflammation, but, except for brain, constitutive expression is low. It has been generally accepted that physiologic renal production of prostaglandins is mediated by COX-1. However, in the absence of inflammation, low levels of COX-2 mRNA are also detectable in the kidney. To examine the role of COX-2 in the kidney and determine its intrarenal localization, we used a 1.3-kb cDNA probe specific for the 3' untranslated region of rat COX-2 and COX-2-specific antiserum. The COX-2-specific cDNA probe hybridized with a 4.4-kb transcript in total RNA from adult rat kidney. Immunoblots of microsomes isolated from kidney cortex and papilla indicated immunoreactive COX-2 in both locations. In situ hybridization and immunohistochemistry indicated that renal cortical COX-2 expression was localized to the macula densa of the juxtaglomerular apparatus and to adjacent epithelial cells of the cortical thick ascending limb of Henle. In addition, COX-2 immunoreactivity was detected in interstitial cells in the papilla. No COX-2 message or immunoreactive protein was detected in arterioles, glomeruli, or cortical or medullary collecting ducts. When animals were chronically sodium restricted, the level of COX-2 in the region of the macula densa increased threefold (from 0.86 +/- 0.08 to 2.52 +/- 0.43/mm2) and the total area of the COX-2 immunoreactive cells in cortex increased from 34 microns2/mm2 of cortex to 226 microns2/mm2 of cortex. The intrarenal distribution of COX-2 and its increased expression in response to sodium restriction suggest that in addition to its proposed role in inflammatory and growth responses, this enzyme may play an important role in the regulation of salt, volume, and blood pressure homeostasis.

860 citations


Journal ArticleDOI
TL;DR: In this article, the reliability measurement of qualitative data is important to determine the reliability of the qualitative data used in the analysis of marketing and applied marketing research, and it is discussed in detail.
Abstract: Data based on qualitative judgments are prevalent in both academic research in marketing and applied marketing research. Reliability measurement of qualitative data is important to determine the st...

859 citations


Journal ArticleDOI
TL;DR: In this paper, the authors evaluated the impact of a new therapy that includes pressure-controlled inverse ratio ventilation followed by extracorporeal CO2 removal on the survival of patients with severe ARDS in a randomized controlled clinical trial.
Abstract: The impact of a new therapy that includes pressure-controlled inverse ratio ventilation followed by extracorporeal CO2 removal on the survival of patients with severe ARDS was evaluated in a randomized controlled clinical trial. Computerized protocols generated around-the-clock instructions for management of arterial oxygenation to assure equivalent intensity of care for patients randomized to the new therapy limb and those randomized to the control, mechanical ventilation limb. We randomized 40 patients with severe ARDS who met the ECMO entry criteria. The main outcome measure was survival at 30 days after randomization. Survival was not significantly different in the 19 mechanical ventilation (42%) and 21 new therapy (extracorporeal) (33%) patients (p = 0.8). All deaths occurred within 30 days of randomization. Overall patient survival was 38% (15 of 40) and was about four times that expected from historical data (p = 0.0002). Extracorporeal treatment group survival was not significantly different from other published survival rates after extracorporeal CO2 removal. Mechanical ventilation patient group survival was significantly higher than the 12% derived from published data (p = 0.0001). Protocols controlled care 86% of the time. Average PaO2 was 59 mm Hg in both treatment groups. Intensity of care required to maintain arterial oxygenation was similar in both groups (2.6 and 2.6 PEEP changes/day; 4.3 and 5.0 FIO2 changes/day). We conclude that there was no significant difference in survival between the mechanical ventilation and the extracorporeal CO2 removal groups. We do not recommend extracorporeal support as a therapy for ARDS. Extracorporeal support for ARDS should be restricted to controlled clinical trials.

822 citations


Journal ArticleDOI
TL;DR: For example, Hamilton et al. as mentioned in this paper found that individuals who had been induced to feel happy rendered more stereotypic judgments than did those in a neutral mood, except under conditions in which they had been told that they would be held accountable for their judgments.
Abstract: Four experiments examined the effects of happiness on the tendency to use stereotypes in social judgment. In each experiment, individuals who had been induced to feel happy rendered more stereotypic judgments than did those in a neutral mood. Experiment 1 demonstrated this phenomenon with a mood induction procedure that involved recalling life experiences. Experiments 2 and 3 suggested that the greater reliance on stereotypes evident in the judgments of happy individuals was not attributable to cognitive capacity deficits created by intrusive happy thoughts or by cognitively disruptive excitement or energetic arousal that may accompany the experience of happiness. In Experiment 4, happy individuals again were found to render more stereotypic judgments, except under conditions in which they had been told that they would be held accountable for their judgments. These results suggest that although happy people's tendency to engage in stereotypic thinking may be pervasive, they are quite capable of avoiding the influence of stereotypes in their judgments when situational factors provide a motivational impetus for such effort. Discovering the conditions under which group stereotypes are likely to be applied in forming impressions of and making judgments about individuals has been an issue of perennial interest in social psychology. Factors such as information overload (Pratto & Bargh, 1991; Stangor & Duan, 1991) and task difficulty (Bodenhausen & Lichtenstein, 1987), for example, have been shown to increase the social perceiver's reliance on stereotypic preconceptions (for a review, see Hamilton & Sherman, in press). In the present research, we investigated the role of emotion, specifically happiness, in the application of stereotypes during social information processing. Does being happy have any impact on the likelihood of stereotyping others? If so, what is the mechanism involved? It was these questions that we sought to address. Interest in the relationship between emotion and stereotyping is certainly not new. However, previous attempts to understand the role of affective experience in prejudice and stereotyping have focused almost exclusively on the impact of negative emotions. Conventional wisdom indicates that it is during times of stress, anxiety, or hostility that prejudice and stereotypes are most likely to emerge and exert their influence on social perception. Psychological research lends credence to the idea that anger, conflict, frustration, and anxiety are indeed associated with

Journal ArticleDOI
TL;DR: In this paper, the authors proposed a hybrid of a stochastic frontier regression and a truncated regression to estimate the production frontier with non-neutral shifting of the average production function.
Abstract: This article proposed a hybrid of a stochastic frontier regression The proposed model and estimation differ from the conventional model of Aigner, Lovell, and Schmidt The model combines a stochastic frontier regression and a truncated regression to estimate the production frontier with non-neutral shifting of the average production function The truncated regression identifies the sources of efficiency The article presents empirical evidence of non-neutral effects of the firm's characteristics—the age of the firms, the export ratio, and the R&D expenditure—on the frontier production function and production efficiency in the Taiwan's electronics industry

Journal ArticleDOI
TL;DR: It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important in order to address the recent plethora of potential therapeutic agents for the prevention and treatment of AR DS.
Abstract: The acute respiratory distress syndrome (ARDS), a process of non-hydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies carries a high morbidity, mortality (10-90%) and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged and may be different in Europe. Part of the reason for these uncertainties is the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those whose wish to know the true incidence and outcome on this clinical syndrome are stymied. The European American Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important in order to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS.

Journal ArticleDOI
TL;DR: Data from the arthritis and chronic pain subjects established that the Form C subscales were moderately stable over time and possessed considerable concurrent and construct validity.
Abstract: Form C of the Multidimensional Health Locus of Control (MHLC) scales is an 18 item, general purpose, condition-specific locus of control scale that could easily be adapted for use with any medical or health-related condition. Data from 588 patients with one of four conditions--rheumatoid arthritis, chronic pain, diabetes, or cancer--were utilized to establish the factor structure of Form C and to establish the reliability and validity of the resultant four subscales: Internality; Chance; Doctors; and Other (powerful) People. The alpha reliabilities of the subscales are adequate for research purposes. Data from the arthritis and chronic pain subjects established that the Form C subscales were moderately stable over time and possessed considerable concurrent and construct validity. Some discriminant validity of Form C with Form B of the MHLC was also demonstrated.

Journal ArticleDOI
TL;DR: It is concluded that liposomes and niosomes may become a useful dosage form for a variety of dermally active compounds, specifically due to their ability to modulate drug transfer and serve as nontoxic penetration enhancers.

Journal ArticleDOI
TL;DR: Sequencing data suggest that sequence divergence in vacA genes may explain the lack of functionally active cytotoxin production by some H. pylori isolates.

Book ChapterDOI
01 Jan 1994
TL;DR: In this paper, the geometry of discrete groups of isometries of S n, E n, and H n is studied, and the basic properties of fundamental domains for a discrete group are examined in Sections 6.2, 6.3, and 6.4.
Abstract: In this chapter, we study the geometry of discrete groups of isometries of S n , E n , and H n . The chapter begins with an introduction to the projective disk model of hyperbolic n-space. Convex sets, polyhedra, and polytopes in S n , E n , and H n are studied in Sections 6.2, 6.3, and 6.4, respectively. The basic properties of fundamental domains for a discrete group are examined in Sections 6.5 and 6.6. The chapter ends with a study of the basic properties of tessellations of S n , E n , and H n .

Journal Article
TL;DR: It is suggested that abnormal methylation could account for transcriptional inactivation of the estrogen receptor gene and subsequent hormone resistance in some human breast cancers.
Abstract: Breast cancer is the most common malignancy in women and hormone resistance is a challenging problem in its treatment. Loss of estrogen receptor expression is an important means of hormone resistance, but the mechanisms involved are poorly understood. We now demonstrate a potential role for abnormal DNA methylation in transcriptional inactivation of the estrogen receptor gene. Estrogen receptor-negative human breast cancer cells growing in culture lack estrogen receptor mRNA, have a higher capacity to methylate DNA, and display extensive methylation of the CpG island in the 5' promoter region of the estrogen receptor gene, which would correlate with silencing of expression. These results suggest that abnormal methylation could account for transcriptional inactivation of the estrogen receptor gene and subsequent hormone resistance in some human breast cancers.

Journal ArticleDOI
TL;DR: The 17-item Emotional Expressivity Scale (EES) was designed as a self-report measure of the extent to which people outwardly display their emotions, and reliability studies showed the EES to be an internally consistent and stable individual-difference measure.
Abstract: Although emotional expressivity figures prominently in several theories of psychological and physical functioning, limitations of currently available measurement techniques impede precise and economical testing of these theories. The 17-item Emotional Expressivity Scale (EES) was designed as a self-report measure of the extent to which people outwardly display their emotions. Reliability studies showed the EES to be an internally consistent and stable individual-difference measure. Validational studies established initial convergent and discriminant validities, a moderate relationship between self-rated and other-rated expression, and correspondence between self-report and laboratorymeasured expressiveness using both college student and community populations. The potential for the EES to promote and integrate findings across diverse areas of research is discussed. Other peoples' emotional expressions hold a certain fascination for nearly everyone. News agencies always provide images of politicians' expressions on winning and losing elections. Reports of court cases routinely mention the defendant's emotional expressions during the reading of the verdict. Winning and losing locker-room photographs attempt to capture sports figures' expressive reactions. This level of fascination is probably supported by the belief that something unique and interesting is communicated by emotional expressions—something that words may at times fail to express. As Fritz Perls (1969), the founder of Gestalt therapy, put it "What we say is mostly either lies or bullshit. But the voice is there, the gesture, the posture, the facial expression" (p. 54). People vary in the extent to which they outwardly exhibit emotions, and these differences have long posed unique and interesting challenges to psychologists. Indeed, emotional expressiveness has captured the attention of researchers interested in areas as diverse as nonverbal communication, psychopathology, personality, social psychology, and health psychology. This article reports on the development of a new self-report measure capturing the general disposition to outwardly express emotion. At the outset, it is worth addressing several crucial questions. Can emotional expressiveness be defined operationally? Is emo

Journal ArticleDOI
TL;DR: Studies of the heterogeneity, function, and regulation of cAK and cGK have provided insight into the enzymology of diverse protein kinases and into the roles of these kinases in cellular processes.
Abstract: Cyclic AMP-dependent protein kinase (cAK) was first described in 19631964 (43, 132) as a cAMP-dependent glycogen synthase kinase that, in the presence of Mg/ A TP, transferred the 'V-phosphate of A TP to serines or threonines on many cellular enzymes. It was found to phosphorylate a number of proteins and was permanently named in 1968 (168). Ensuing years produced vast numbers of reports regarding properties of cAK and the signal mechanisms that elicit its activation. Many of these have been reviewed recently (8, 33,47, 85, 141, 155, 181). In 1970 cyclic GMP-de­ pendent protein kinase (cGK) was discovered (86). cGK is homologous in structure and function to cAK (24, 49, 59, 66, 93, 141, 154). The role of cGMP in physiological processes is increasingly appreciated (15, 39, 92, 94, 113, 170), but cGK is only one of several intracellular receptors for cGMP. Studies of the heterogeneity, function, and regulation of cAK and cGK have provided insight into the enzymology of diverse protein kinases and into the roles of these kinases in cellular processes.


Journal ArticleDOI
TL;DR: In this paper, a regression model with fixed-effects and national individual-level panel0 data (1966-81) was used to decompose the sex gap in pay, and net positive returns to individuals' education and experience and to occupations' cognitive and physical skills were found.
Abstract: A regression model with fixed-effects and national individual-level panel0 data (1966-81) is used to decompose the sex gap in pay. In accordance with neoclassical predictions from human capital theory, net positive returns to individuals' education and experience and to occupations' cognitive and physical skills are found. While sex differences in experience have large effects on the sex gap skill contributes little to the gap. In accordance with cultural feminist predictions, negative returns to being in an occupation with a higher percentage of females or requiring more nurturant social skill are found. These forms of gendered valuation contribute significantly to the sex gap in pay. In contrast to the neoclassical prediction of compensating differentials, the analysis did not find consistently positive effects for onerous physical conditions, nor did these have much effect on the gap.

Journal ArticleDOI
10 Nov 1994-Nature
TL;DR: The phenotype of 5LX-/- mice under injurious insult identifies the role for leukotrienes in the pathophysiology of select inflammatory states and disrupts the 5-lipoxygenase gene by homologous recombination in embryonic stem cells.
Abstract: Leukotrienes constitute a class of potent biological mediators of inflammation and anaphylaxis (for reviews see refs 1 and 2). Their biosynthesis derives from 5-lipoxygenase-catalysed oxygenation of arachidonic acid in granulocytes, macrophages and mast cells. To examine the physiological importance of leukotrienes, we have disrupted the 5-lipoxygenase gene by homologous recombination in embryonic stem cells. 5-Lipoxygenase-deficient (5LX-/-) mice develop normally and are healthy. They show a selective opposition to certain inflammatory insults. Although there is no difference in their reaction to endotoxin shock, the 5LX-/- animals resist the lethal effects of shock induced by platelet-activating factor. Reaction to ear inflammation induced by phorbol ester is normal, whereas inflammation induced by arachidonic acid is markedly reduced. Contrasts were also found in two models of leukocyte chemotaxis in vivo. The phenotype of 5LX-/- mice under injurious insult identifies the role for leukotrienes in the pathophysiology of select inflammatory states.

Journal ArticleDOI
TL;DR: The derivation of multiple embryonic germ cell lines from 8.5 days post coitum embryos of C57BL/6 inbred mice are reported, showing that pluripotent cell lines capable of forming teratocarcinomas and coat color chimeras can be established from primordial germ cells of 8.0 days p.c.
Abstract: Primordial germ cells of the mouse cultured on feeder layers with leukemia inhibitory factor, Steel factor and basic fibroblast growth factor give rise to cells that resemble undifferentiated blastocyst-derived embryonic stem cells. These primordial germ cell-derived embryonic germ cells can be induced to differentiate extensively in culture, form teratocarcinomas when injected into nude mice and contribute to chimeras when injected into host blastocysts. Here, we report the derivation of multiple embryonic germ cell lines from 8.5 days post coitum embryos of C57BL/6 inbred mice. Four independent embryonic germ cell lines with normal male karyotypes have formed chimeras when injected into BALB/c host blastocysts and two of these lines have transmitted coat color markers through the germline. We also show that pluripotent cell lines capable of forming teratocarcinomas and coat color chimeras can be established from primordial germ cells of 8.0 days p.c. embryos and 12.5 days p.c. genital ridges. We have examined the methylation status of the putative imprinting box of the insulin-like growth factor type 2 receptor gene (Igf2r) in these embryonic germ cell lines. No correlation was found between methylation pattern and germline competence. A significant difference was observed between embryonic stem cell and embryonic germ cell lines in their ability to maintain the methylation imprint of the Igf2r gene in culture. This may illustrate a fundamental difference between these two cell types.

Journal ArticleDOI
TL;DR: Fibroadenoma is a long-term risk factor for breast cancer and the risk is increased in women with complex fibroadenomas, proliferative disease, or a family history of breast cancer.
Abstract: Background Fibroadenomas are benign breast tumors that are commonly diagnosed in young women and are associated with a slight increase in the risk of breast cancer. These lesions vary considerably in their histologic characteristics. We assessed the correlation between the histologic features of fibroadenomas and the risk of subsequent breast cancer. Methods We conducted a retrospective cohort study of a consecutive series of patients with fibroadenoma diagnosed between 1950 and 1968. Follow-up data were obtained for 1835 patients (90 percent of those eligible). Fibroadenomas with cysts, sclerosing adenosis, epithelial calcifications, or papillary apocrine changes were classified as complex. The rate of subsequent breast cancer among the patients was compared with the rates in two control groups, women listed in the Connecticut Tumor Registry and women chosen from among the patients' sisters-in-law. Results The risk of invasive breast cancer was 2.17 times higher among the patients with fibroadenoma than ...

Journal ArticleDOI
23 Nov 1994-JAMA
TL;DR: Physicians who have been sued frequently are more often the objects of complaints about the interpersonal care they provide even by their patients who do not sue.
Abstract: Objective. —To examine the relationship between prior physician malpractice experience and patients' satisfaction with care. Design. —Women were interviewed using a questionnaire that contained structured and open-ended questions. Participants. —Mothers of all stillborn infants, infant deaths, and a random sampling of viable infants drawn from 1987 Florida Vital Statistics were sorted into four groups based on the malpractice claims experience of their obstetricians between 1983 and 1986. Interviews were completed with 963 of 1536 women, most by telephone, 53 by in-person interview. Main Outcome Measures. —Mothers' responses to closed-ended and open-ended questions about their perceptions of the care they received during their pregnancy, labor, and delivery. Results. —Even though none of the women actually filed a claim, a consistent pattern of differences emerged when comparing women's perceptions of care received. Patients seeing physicians with the most frequent numbers of claims but without high payments were significantly more likely to complain that they felt rushed, never received explanations for tests, and were ignored. In response to the open-ended question, "What part of your care were you least satisfied with?" women seeing physicians in the High Frequency malpractice risk group offered twice as many complaints as those seeing physicians who had never been sued. Problems with physician-patient communication were the most commonly offered complaints. Conclusion. —Physicians who have been sued frequently are more often the objects of complaints about the interpersonal care they provide even by their patients who do not sue. (JAMA. 1994;272:1583-1587)

Journal ArticleDOI
01 Nov 1994-Nature
TL;DR: This work presents the first empirical evidence that a strong nega-tive effect exists in the yucca/yucca moth interaction and shows a strong positive effect between the number of pollinations received and the probability of flower retention, which can explain the stability of this type of interaction.
Abstract: INTERSPECIFIC mutualisms inherently possess a conflict of interests between the interacting species in that fitness increases of one species occur at the expense of the other. This holds for mutualisms as diverse as plant associations with mycorrhizal fungi or nitrogen-fixing bacteria, animals and endosymbionts, and obligate plant-pollinator associations1–6. Prevailing models of interspecific cooperation predict that mutualistic interactions are evolutionary stable only when both interacting species possess mechanisms to prevent excessive exploitation3–6. In light of this, it is paradoxical that some of the classical examples of coevolved obligate mutualism seemingly do not meet this criterion. In mutualisms involving seed parasites that actively pollinate their hosts, such as yucca/ yucca moth and fig/fig wasp interactions, there is no apparent means of retaliation on behalf of the plant. Predictions from theory suggest that a cryptic mechanism, such as selective abortion of flowers with heavy egg loads, could stabilize these interactions4,6–9. Here we present the first empirical evidence that such a mechanism in fact exists in the yucca/yucca moth interaction. A strong nega-tive effect exists between moth egg number and probability of flower retention. Furthermore, we show a strong positive effect between the number of pollinations received and the probability of flower retention. Selective maturation of fruit with low egg loads and high pollen loads provides a mechanism to increase the quantity and possibly quality of seeds produced, and simultaneously select against moths that lay many eggs per flower or provide low-quality pollinations4,6,8,10. Not only can these results explain the stability of this type of interaction, but selection for high-quality pollination also provides a mechanism to help explain the evolution of active pollination among yucca moths.

Journal ArticleDOI
TL;DR: In this article, over 70 empirical studies of entry and exit patterns covering eleven different countries generally support the expectation that entry is more frequent in more profitable, rapidly growing industries, and slower where the absolute costs of capital required to build a minimum efficient scale plant are imposing.
Abstract: Over 70 empirical studies of entry and exit patterns covering eleven different countries generally support the expectation that entry is more frequent in more profitable, rapidly growing industries, and slower where the absolute costs of capital required to build a minimum efficient scale plant are imposing. Scale economies, excess capacity, and limit pricing receive little empirical support as entry impediments. The evidence concerning the effects of advertising and R&D intensity is confusing. Exit is faster where profits are lower, and slower where durable specific (sunk) capital costs are more important. Exit and entry are strongly correlated, probably due to displacement (of incumbents by more efficient entrants) and vacuum effects (in which entrants are enticed by the prospects of selling to uncommitted customers abandoned by a recent exit).

Journal ArticleDOI
TL;DR: A mitogen-inducible cyclooxygenase gene is shown to be regulated by TGF alpha and TPA in rat intestinal epithelial cells and it is suggested that products of an intestinal growth factor-inducing cyclo oxygengenase may play a role in the regulation of mitogenesis.
Abstract: Growth factors and tumor promoters have been shown to play a role in intestinal epithelial growth regulation and transformation. In this study, transforming growth factor-alpha (TGF alpha) and the tumor promoter, tetradecanoyl phorbol acetate (TPA), are shown to stimulate the production of eicosanoids by rat intestinal epithelial (RIE-1) cells in culture. A 4.5-kb mRNA, which hybridizes to the mouse cyclooxygenase-2 cDNA probe, is elevated 18-fold within 30 min after TGF alpha or TPA treatment. Stimulation of RIE-1 cells with TGF alpha leads to the increase of a protein (M(r) approximately 69,000), which binds a monospecific antibody to the mouse cyclooxygenase-2 protein. Dexamethasone markedly inhibits the increase of the 4.5-kb mRNA. Pretreatment of TGF alpha or TPA-stimulated RIE-1 cells with dexamethasone or cyclooxygenase inhibitors prevents the increase in eicosanoid production by these cells. Treatment of quiescent RIE-1 cells with TGF alpha stimulates mitogenesis. This mitogenic activity is blocked by pretreating the cells with dexamethasone or cyclooxygenase inhibitors. A mitogen-inducible cyclooxygenase gene is thus shown to be regulated by TGF alpha and TPA in rat intestinal epithelial cells. We suggest that products of an intestinal growth factor-inducible cyclooxygenase may play a role in the regulation of mitogenesis.

Journal ArticleDOI
TL;DR: Cold-adapted and inactivated influenza vaccines are safe and effective for preventing influenza A disease and significantly increased hemagglutination inhibition antibody titers.
Abstract: A double-blind, randomized controlled trial over 5 years compared the safety, immunogenicity, and efficacy of cold-adapted and inactivated influenza A vaccines in 5210 normal subjects. Both vaccines were well tolerated. Inactivated vaccine significantly increased hemagglutination inhibition antibody titers. Significant titer rises were also noted after cold-adapted vaccine but of lesser magnitude than with inactivated vaccine. The efficacy of inactivated vaccine in preventing culture-positive influenza was 76% (95% confidence interval [CI], 58%-87%) for H1N1 disease and 74% (95% CI, 52%-86%) for H3N2; for cold-adapted vaccine, 85% (95% CI, 70%-92%) and 58% (95% CI, 29%-75%), respectively. The efficacy of inactivated vaccine in preventing a four-fold rise in antibody titer over the influenza season was 69% (95% CI, 61%-76%) for H1N1 and 73% (95% CI, 65%-79%) for H3N2; for cold-adapted vaccine, 54% (95% CI, 44%-62%) and 32% (95% CI, 17%-44%), respectively. Cold-adapted and inactivated influenza vaccines are safe and effective for preventing influenza A disease.