Showing papers by "Columbia University published in 1991"

Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis

Abstract: Background Without strong evidence of benefit, the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s, then declined. Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis. Methods We conducted a randomized trial at 50 clinical centers throughout the United States and Canada, in patients in two predetermined strata based on the severity of carotid stenosis--30 to 69 percent and 70 to 99 percent. We report here the results in the 659 patients in the latter stratum, who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery. All patients received optimal medical care, including antiplatelet therapy. Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons. All patients were examined by neurologists 1, 3, 6, 9, and 12 months after entry and then every 4 months. End points were assessed by blinded, independent case review. No patient was lost to follow-up. Results Life-table estimates of the cumulative risk of any ipsilateral stroke at two years were 26 percent in the 331 medical patients and 9 percent in the 328 surgical patients--an absolute risk reduction (+/- SE) 17 +/- 3.5 percent (P less than 0.001). For a major or fatal ipsilateral stroke, the corresponding estimates were 13.1 percent and 2.5 percent--an absolute risk reduction of 10.6 +/- 2.6 percent (P less than 0.001). Carotid endarterectomy was still found to be beneficial when all strokes and deaths were included in the analysis (P less than 0.001). Conclusions Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high-grade stenosis (70 to 99 percent) of the internal carotid artery.

Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons.

Abstract: We demonstrate in this work that the surface tension, water-organic solvent, transfer-free energies and the thermodynamics of melting of linear alkanes provide fundamental insights into the nonpolar driving forces for protein folding and protein binding reactions. We first develop a model for the curvature dependence of the hydrophobic effect and find that the macroscopic concept of interfacial free energy is applicable at the molecular level. Application of a well-known relationship involving surface tension and adhesion energies reveals that dispersion forces play little or no net role in hydrophobic interactions; rather, the standard model of disruption of water structure (entropically driven at 25 degrees C) is correct. The hydrophobic interaction is found, in agreement with the classical picture, to provide a major driving force for protein folding. Analysis of the melting behavior of hydrocarbons reveals that close packing of the protein interior makes only a small free energy contribution to folding because the enthalpic gain resulting from increased dispersion interactions (relative to the liquid) is countered by the freezing of side chain motion. The identical effect should occur in association reactions, which may provide an enormous simplification in the evaluation of binding energies. Protein binding reactions, even between nearly planar or concave/convex interfaces, are found to have effective hydrophobicities considerably smaller than the prediction based on macroscopic surface tension. This is due to the formation of a concave collar region that usually accompanies complex formation. This effect may preclude the formation of complexes between convex surfaces.

Growth in Cities

Abstract: Recent theories of economic growth, including Romer (1986), Porter (1989) and Jacobs (1969), have stressed the role of technological spillovers in generating growth. Because such knowledge spillovers are particularly effective in cities, where communication between people is more extensive, data on the growth of industries in different cities allows us to test some of these theories. Using a new data set on the growth of large industries in 170 U.S. cities between 1956 and 1987, we find that local competition and urban variety, but not regional specialization, encourage employment growth in industries. The evidence suggests that important knowledge spillovers might be between, rather than within industries, consistent with the theories of Jacobs (1969).

Managerial Fads and Fashions: The Diffusion and Rejection of Innovations

Abstract: Reviews indicate that the dominant perspective in the diffusion of innovation literature contains proinnovation biases which suggest that innovations and the diffusion of innovations will benefit adopters. As a result, it is difficult to either address or begin answering the questions: when and how do technically inefficient innovations diffuse? or when and how are technically efficient innovations rejected? This article has two goals: (1) to develop a typology that focuses attention on three less dominant perspectives that can be used to guide research on these questions and (2) to suggest how organizational scientists can develop more encompassing theories of innovation diffusion and rejection by using the theoretical tensions that exist between the dominant perspective and the three perspectives developed in this article. These resolutions are important because they indicate that processes which prompt the adoption of efficient innovations may coexist with processes that prompt the adoption of ineffici...

Conceptualization and Rationale for Consensus Definitions of Terms in Major Depressive Disorder: Remission, Recovery, Relapse, and Recurrence

Abstract: • In 1988, the MacArthur Foundation Research Network on the Psychobiology of Depression convened a task force to examine the ways in which change points in the course of depressive illness had been described and the extent to which inconsistency in these descriptions might be impeding research on this disorder. We found considerable inconsistency across and even within research reports and concluded that research on depressive illness would be well served by greater consistency in the definition change points in the course of illness. We propose an internally consistent, empirically defined conceptual scheme for the terms remission, recovery , relapse , and recurrence . In addition, we propose tentative operational criteria for each term. Finally, we discuss ways to assess the usefulness of such operational criteria through reanalysis of existing data and the design and conduct of new experiments.

Why do firms differ, and how does it matter?

Abstract: In virtually all economic analyses, differences among firms in the same line of business are repressed, or assumed to reflect differences in the market environments that they face. In contrast, for students of business management and strategy, firm differences are at the heart of their inquiry. This paper explores the reasons behind this stark difference in viewpoint. It argues that economists really ought to recognize firm differences explicitly.

The skills of argument

Abstract: Introduction Scope of the Investigation The investigation to be described focuses on an individual's thinking processes, and as such it relates most directly to the sizable psychological literature on thinking and reasoning. Yet the work also addresses issues that are prominent in a number of other disciplines. From a philosophical perspective, the present work relates to an increasing interest shown by philosophers in the nature and logic of natural language argumentation (Walton, 1989). As already mentioned, philosophers of education such as Scheffler (1965) have noted the importance of reflective thinking about thought, but their ideas have not been connected explicitly to the analysis of argumentation. Here we offer those with philosophical interests an analysis of elementary argumentive reasoning that is grounded in empirical data about the competencies and incompetencies that people exhibit in their argumentive reasoning about everyday topics. From a language perspective, the present work relates to a growing area of research within discourse analysis pertaining to discourse that is argumentive (Grimshaw, 1990). What are the unique features that characterize argumentive in contrast to other kinds of discourse? Although it does not investigate social discourse directly, the research presented here, focused on the cognitive prerequisites of competent argument, offers some insight regarding the language of argument. From sociological and political perspectives, the present work is relevant to a growing understanding of the complex interrelations that exist between individual and sociological processes (Dowd, 1990).

Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1

Abstract: THE zinc-finger transcription factor GATA-1 (previously known as GF-1, NF-E1 or Eryf 1 (refs 1-5)) binds to GATA consensus elements in regulatory regions of theα- and β-globin gene clusters2–6 and other erythroid cell-specific genes7–9. Analysis of the effects of mutations in GATA-binding sites in cell culture and in binding assays in vitro2,5,10,11, as well as transactivation studies with GATA-1 expression vectors in heterologous cells12, have provided indirect evidence that this factor is involved in the activation of globin and other genes during erythroid cell maturation. GATA-1 is also expressed in megakaryocytes13,14 and mast cells13, but not in other blood cell lineages or in non-haemopoietic cells. To investigate the role of this factor in haematopoiesis in vivo. we disrupted the X-linked GATA-1 gene by homologous recombination in a male (XY) murine embryonic stem cell line and tested the GATA-1-deficient cells for their ability to contribute to different tissues in chimaeric mice. The mutant embryonic stem cells contributed to all non-haemopoietic tissues tested and to a white blood cell fraction, but failed to give rise to mature red blood cells. This demonstrates that GATA-1 is required for the normal differentiation of erythroid cells, and that other GATA-binding proteins15,16 cannot compensate for its absence.

A rapid finite difference algorithm, utilizing successive over-relaxation to solve the Poisson-Boltzmann equation

Abstract: An efficient algorithm is presented for the numerical solution of the Poisson–Boltzmann equation by the finite difference method of successive over-relaxation. Improvements include the rapid estimation of the optimum relaxation parameter, reduction in number of operations per iteration, and vector-oriented array mapping. The algorithm has been incorporated into the electrostatic program DelPhi, reducing the required computing time by between one and two orders of magnitude. As a result the estimation of electrostatic effects such as solvent screening, ion distributions, and solvation energies of small solutes and biological macromolecules in solution, can be performed rapidly, and with minimal computing facilities.

Openness and Growth: A Time-Series, Cross-Country Analysis for Developing Countries

Abstract: This paper compares the association between many popular proxies for openness and the rate of GDP growth, as well as the results from cross-section and panel estimation, controlling for country effects. The results suggest that using period averages versus annual data critically affects the strength of the association between openness and growth. The paper reviews the empirical literature on openness and technological change. It discusses the dataset for this paper and the empirical specification, while also presenting the main results. The sensitivity of the results to the inclusion of both macroeconomic variables and country size are also tested. It concludes with an agenda for future research.

Dividend Yields and Expected Stock Returns: Alternative Procedures for Interference and Measurement

Abstract: Alternative ways of conducting inference and measurement for long-horizon forecasting are explored with an application to dividend yields as predictors of stock returns. Monte Carlo analysis indicates that the Hansen and Hodrick (1980) procedure is biased at long horizons, but the alternatives perform better. These include an estimator derived under the null hypothesis as in Richardson and Smith (1989), a reformulation of the regression as in Jegadeesh (1990), and a vector autoregression (VAR) as in Campbell and Shiller (1988), Kandel and Stambaugh (1988), and Campbell (1991). The statistical properties of long-horizon statistics generated from the VAR indicate interesting patterns in expected stock returns.

A triphasic theory for the swelling and deformation behaviors of articular cartilage.

Abstract: Swelling of articular cartilage depends on its fixed charge density and distribution, the stiffness of its collagen-proteoglycan matrix, and the ion concentrations in the interstitium. A theory for a tertiary mixture has been developed, including the two fluid-solid phases (biphasic), and an ion phase, representing cation and anion of a single salt, to describe the deformation and stress fields for cartilage under chemical and/or mechanical loads. This triphasic theory combines the physico-chemical theory for ionic and polyionic (proteoglycan) solutions with the biphasic theory for cartilage. The present model assumes the fixed charge groups to remain unchanged, and that the counter-ions are the cations of a single-salt of the bathing solution. The momentum equation for the neutral salt and for the intersitial water are expressed in terms of their chemical potentials whose gradients are the driving forces for their movements. These chemical potentials depend on fluid pressure p, salt concentration c, solid matrix dilatation e and fixed charge density cF. For a uni-uni valent salt such as NaCl, they are given by mu i = mu io + (RT/Mi)ln[gamma 2 +/- c(c + cF)] and mu w = mu wo + [p-RT phi (2c + cF) + Bwe]/pwT, where R, T, Mi, gamma +/-, phi, pwT and Bw are universal gas constant, absolute temperature, molecular weight, mean activity coefficient of salt, osmotic coefficient, true density of water, and a coupling material coefficient, respectively. For infinitesimal strains and material isotropy, the stress-strain relationship for the total mixture stress is sigma = - pI-TcI + lambda s(trE)I + 2 musE, where E is the strain tensor and (lambda s, mu s) are the Lame constants of the elastic solid matrix. The chemical-expansion stress (-Tc) derives from the charge-to-charge repulsive forces within the solid matrix. This theory can be applied to both equilibrium and non-equilibrium problems. For equilibrium free swelling problems, the theory yields the well known Donnan equilibrium ion distribution and osmotic pressure equations, along with an analytical expression for the "pre-stress" in the solid matrix. For the confined-compression swelling problem, it predicts that the applied compressive stress is shared by three load support mechanisms: 1) the Donnan osmotic pressure; 2) the chemical-expansion stress; and 3) the solid matrix elastic stress. Numerical calculations have been made, based on a set of equilibrium free-swelling and confined-compression data, to assess the relative contribution of each mechanism to load support. Our results show that all three mechanisms are important in determining the overall compressive stiffness of cartilage.

Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger.

Abstract: Although long-term potentiation (LTP) in the CA1 region of the hippocampus is initiated postsynaptically by the influx of Ca2+ through N-methyl-D-aspartate receptor channels, the maintenance of LTP seems to be at least in part presynaptic. This suggests that the postsynaptic cell releases a retrograde messenger to activate the presynaptic terminals. It is likely that this messenger is membrane-permeant and reaches the presynaptic neuron by diffusion. We therefore have investigated two major membrane-permeant candidate retrograde messengers, arachidonic acid and nitric oxide (NO). Consistent with arachidonic acid or a lipoxygenase metabolite being a retrograde messenger, the phospholipase A2 and lipoxygenase inhibitor nordihydroguaiaretic acid blocked LTP in the guinea pig CA1 region in vitro. However, arachidonic acid (up to 100 microM) did not reliably produce activity-independent LTP, and activity-dependent potentiation by arachidonic acid was blocked by DL-aminophosphonovaleric acid. Since nordihydroguaiaretic acid also interferes with signal transduction involving NO, we next examined whether inhibitors of NO synthase block LTP. NG-Nitro-L-arginine blocked LTP when given in the bath, and this inhibition was partially overcome by high concentrations of L-arginine, suggesting that the inhibitor is specific to NO synthase. NG-Nitro-L-arginine and NG-methyl-L-arginine (but not NG-methyl-D-arginine) also blocked LTP when injected intracellularly, indicating that NO synthase is located in the postsynaptic cell. The NO, in turn, seems to be released into the extracellular space, since bathing the slice with hemoglobin, a protein that binds NO and is not taken up by cells, also blocked LTP. Moreover, NO enhances spontaneous presynaptic release of transmitter from hippocampal neurons in dissociated cell culture. These data favor the idea that NO might be a retrograde messenger in LTP.

p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia.

Abstract: We have investigated the frequency of p53 mutations in B- and T-cell human lymphoid malignancies, including acute lymphoblastic leukemia, the major subtypes of non-Hodgkin lymphoma, and chronic lymphocytic leukemia. p53 exons 5-9 were studied by using genomic DNA from 197 primary tumors and 27 cell lines by single-strand conformation polymorphism analysis and by direct sequencing of PCR-amplified fragments. Mutations were found associated with (i) Burkitt lymphoma (9/27 biopsies; 17/27 cell lines) and its leukemic counterpart L3-type B-cell acute lymphoblastic leukemia (5/9), both of which also carry activated c-myc oncogenes, and (ii) B-cell chronic lymphocytic leukemia (6/40) and, in particular, its stage of progression known as Richter's transformation (3/7). Mutations were not found at any significant frequency in other types of non-Hodgkin lymphoma or acute lymphoblastic leukemia. In many cases, only the mutated allele was detectable, implying loss of the normal allele. These results suggest that (i) significant differences in the frequency of p53 mutations are present among subtypes of neoplasms derived from the same tissue; (ii) p53 may play a role in tumor progression in B-cell chronic lymphocytic leukemia; (iii) the presence of both p53 loss/inactivation and c-myc oncogene activation may be important in the pathogenesis of Burkitt lymphoma and its leukemic form L3-type B-cell acute lymphoblastic leukemia.

Three‐dimensional model synthesis of the global methane cycle

Abstract: The geographic and seasonal emission distributions of the major sources and sinks of atmospheric methane were compiled using methane flux measurements and energy and agricultural statistics in conjunction with global digital data bases of land surface characteristics and anthropogenic activities. Chemical destruction of methane in the atmosphere was calculated using three-dimensional OH fields every 5 days taken from Spivakovsky et al. (1990a, b). The signatures of each of the sources and sinks in the atmosphere were simulated using a global three-dimensional tracer transport model. Candidate methane budget scenarios were constructed according to mass balance of methane and its carbon isotopes. The verisimilitude of the scenarios was tested by their ability to reproduce the meridional gradient and seasonal variations of methane observed in the atmosphere. Constraints imposed by all the atmospheric observations are satisfied simultaneously by several budget scenarios. A preferred budget comprises annual destruction rates of 450 Tg by OH oxidation and 10 Tg by soil absorption and annual emissions of 80 Tg from fossil sources, 80 Tg from domestic animals, and 35 Tg from wetlands and tundra poleward of 50°N. Emissions from landfills, tropical swamps, rice fields, biomass burning, and termites total 295 Tg; however, the individual contributions of these terms cannot be determined uniquely because of the lack of measurements of direct fluxes and of atmospheric methane variations in regions where these sources are concentrated.

The Seasons of a Ceo's Tenure

Abstract: This article proposes a model of the dynamics of the CEO's tenure in office. The central argument is that there are discernible phases, or seasons, within an executive's tenure in a position, and that these seasons give rise to distinct patterns of executive attention, behavior, and, ultimately, organizational performance. The five delineated seasons are (a) response to mandate, (b) experimentation, (c) selection of an enduring theme, (d) convergence, and (e) dysfunction. The theoretical and practical implications of the model are discussed.

Defining the sudden infant death syndrome (SIDS): deliberations of an expert panel convened by the National Institute of Child Health and Human Development.

Abstract: (1991). Defining the Sudden Infant Death Syndrome (Sids): Deliberations of an Expert Panel Convened by the National Institute of Child Health and Human Development. Pediatric Pathology: Vol. 11, No. 5, pp. 677-684.

Prevalence of epilepsy in Rochester, Minnesota: 1940-1980.

Abstract: Summary: : The prevalence of epilepsy in Rochester, Minnesota has been determined for a specific date in each of 5 decennial census years. Individuals with a diagnosis of epilepsy (recurrent unprovoked seizures) who were known to have experienced a seizure or who had received antiepileptic medication in the preceding 5 years were considered active prevalence cases. By this definition, the age-adjusted prevalence per 1,000 population, increased steadily from 2.7 in 1940 to 6.8 in 1980. At each of five prevalence dates, for all prevalence cases, 60% had epilepsy manifest by partial seizures, and 75% had no known etiology. Prevalence was higher for males than females for all except the last prevalence day. After 1950, prevalence tended to increase with advancing age and was highest in the oldest age groups. On the average, the 1980 prevalence cases had epilepsy 50% had their first diagnosis in the first 20 years of life. RESUME La prevalence de ľ epilepsie dans le Comtede Rochester, dans le Minnesota, a eteevaluee pour une date precise de chacune des 5 annees du recensement decennal. Les individus pour lesquels le diagnostic ďepilepsie avait ete pose (crises spontanees recurrentes) et qui avaient presente une crise ou recevaient un traitement antiepileptiques dans les 5 annees precedentes, ont ete consideres comme des cas de prevalence active. Selon cette definition, la prevalence ajustee pour Page pour 1000 habitants a agumente constamment de 2.7 en 1940 a 6.8 en 1980. A chacune des 5 dates de prevalence, pour tous les cas, 60% ont presente une epilepsie se manifestant par des crises partielles, et 75% n'avaient pas ďetiologie connue. La prevalence teAait plus elevee chez les hommes que chez les femmes, sauf lors du dernier jour de prevalence. Apres 1950, la prevalence tendait a augmenter avec ľâge, elle etait la plus forte dans les groupes ďâge eleve En moyenne, les cas de 1980 avaient une epilepsie evoluant depuis moins de 10 ans et plus de 50% avaient une epilepsie diagnos-tiquee au cours des 20 premieres annees de vie. RESUMEN Se ha determinado la prevalencia de epilepsyia en Rochester, Minnesota, para una fecha especifica en cada uno de los 5 dece-nios del censo. Individuos con diagnostico de epilepsia “ataques recurrentes sin provocacion” que habian tenido un ataque o recibido medicateon antiepileptica en los 5 anos precedentes, fueron considerados como casos activos de prevalencia. Segun esta definition la prevalencia ajustada a la edad por 1.000 habitantes se incremento continuadamente de 2.7 en 1940 a 6.8 en 1980. En cada una de las 5 fechas de prevalencia para todos los casos prevalentes, el 60% tenia epilepsyia manifestada por ataques parciales y el 75% de etiologia desconocida. La prevalencia fue mas elevada en varones que en hembras en todos los dias de prevalencia excepto el ultimo. Despues de 1950 la prevalencia mostro una tendencia al aumento con incremento de la edad y fue mas elevada en los grupos de mayor edad. Como promedio, los casos de prevalencia en 1980 habian padecido epilepsyia durante menos de 10 anos y mas del 50% tuvieron el primer diagnostico en los primeros 20 anos de su vida. ZUSAMMENFASSUNG Die Praevalenz der Epilepsie in Rochester, Minnesota wurde an einem bestimmten Datum in funf aufeinanderfolgenden Cen-sus-Decenien bestimmt. Personen mit der Diagnose Epilepsie (wiederholte nicht provozierte Anfalle), die einene Anfall erlitten hatten oder Antiepileptika eingenommen hatten wurden als ak-tive Praevalenz-Falle betrachtet. Demnach stieg die altersberei-nigte Praevalenz fur 1000 Einwohner kontinuierlich von 2,7 1940 auf 6,8 1980 an. Zu jedem der funf Praevalenz-Daten aller Praevalenz-Falle manifestierte sich die Epilepsie in 60% durch Partialanfalle, davon 75% ohne bekannte Atiologie. Die Praevalenz war fur Manner hoher als fur Frauen wahrend aller Stichtage, ausgenommen des letzten. Nach 1950 stieg die Praevalenz mit zunehmendem Alter leicht an und erreichte ihren hochsten Wert in der altesten Altersgruppe. Im Durchschnitt hatten 1980 die Praevalen-Falle eine Epilepsie fur weniger als 10 Jahre. Bei mehr als 50% wurde die Erstdiagnose Epilepsie in den ersten 20 Le-bensjahren gestellt.

Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection

Abstract: Infection with human immunodeficiency virus-type 1 (HIV-1) has been associated with avariety of neurologic disorders thought to be caused, directly or indirectly, by HIV-1.1-6 Although these disorders have been described clinically, there is no consensus terminology or criteria for diagnosis. To develop consensus nomenclature and case definitions for HIV-1-associated neurologic conditions for research purposes, the American Academy of Neurology AIDS Task Force convened a working group of neurologists, neuropsychologists, psychiatrists, and sociologists that included representatives of the American Neurological Association, the World Federation of Neurology, the International Neuropsychological Society, the National Academy of Neuropsychology, the American Psychological Association, the American Psychiatric Association, the World Health Organization, and the Centers for Disease Control (CDC). These definitions have been developed in conjunction with the International Classification of Diseases-10 (ICD-10, unpublished draft of the World Health Organization) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV, unpublished draft of the American Psychiatric Association). Although consistent with the ICD-10, the definitions are not identical. HIV-2 may cause similar disorders, but the neurologic manifestations of HIV-2 are unknown and are not addressed in this article.

Surface reflection: physical and geometrical perspectives

Abstract: Reflectance models based on physical optics and geometrical optics are studied. Specifically, the authors consider the Beckmann-Spizzichino (physical optics) model and the Torrance-Sparrow (geometrical optics) model. These two models were chosen because they have been reported to fit experimental data well. Each model is described in detail, and the conditions that determine the validity of the model are clearly stated. By studying reflectance curves predicted by the two models, the authors propose a reflectance framework comprising three components: the diffuse lobe, the specular lobe, and the specular spike. The effects of surface roughness on the three primary components are analyzed in detail. >

Neuronal Networks of the Hippocampus

Abstract: From the Publisher: The questions of how a large population of neurons in the brain functions, how synchronized firing of neurons is achieved, and what factors regulate how many and which neurons fire under different conditions form the central theme of this book. Using a combined experimental-theoretical approach unique in neuroscience, the authors present important new techniques for the physiological reconstruction of a large biological neuronal network. They begin by discussing experimental studies of the CA3 hippocampal region in vitro, focusing on single-cell and synaptic electrophysiology, particularly the effects a single neuron exerts on its neighbors. This is followed by a description of a computer model of the system, first for individual cells then for the entire detailed network, and the model is compared with experiments under a variety of conditions. The results shed significant light into the mechanisms of epilepsy, electroencephalograms, and biological oscillations and provide an excellent test case for theories of neural networks.

De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints.

Abstract: A questionnaire sent to major cytogenetics laboratories in the United States and Canada over a 10-year period collected data on the frequency and outcome of cases with either apparently balanced de novo rearrangements or de novo supernumerary marker chromosomes detected at amniocentesis. Of 377,357 reported amniocenteses, approximately 1/2,000 had a de novo reciprocal translocation, 1/9,000 a Robertsonian translocation, 1/10,000 a de novo inversion, and 1/2,500 an extra structurally abnormal chromosome of unidentifiable origin. The risk of a serious congenital anomaly was estimated to be 6.1% (n = 163) for de novo reciprocal translocations, 3.7% (n = 51) for Robertsonian translocations, and 9.4% (n = 32) for inversions. The combined risk for reciprocal translocations and inversions was 6.7% (95% confidence limits 3.1%-10.3%). The risk of abnormality for extra nonsatellited marker chromosomes was 14.7% (n = 68), and that for satellited marker chromosomes was 10.9% (n = 55). In non-Robertsonian rearrangements, distribution of breakpoints among chromosomes was not as would be expected strictly on the basis of length. Most breaks were stated to occur within G-negative bands, but there was little evidence of particular hot spots among these bands. Nevertheless, there did appear to be a correlation between those bands in which breakage was observed most often and those bands where common or rare fragile sites have been described.

Organizational Information Processing, Competitive Responses, and Performance in the U.S. Domestic Airline Industry

Abstract: This study investigates how firms build competitive advantage by focusing on the actions and responses of rivals in the U.S. domestic airline industry. We identified four attributes of competitive ...

mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases.

Abstract: We studied two related infants with a fatal mitochondrial disease, affecting muscle in one and liver in the other. Quantitative analysis revealed a severe depletion of mtDNA in affected tissues. This genetic abnormality was also observed in muscle of an unrelated infant with myopathy and in muscle and kidney of a fourth child with myopathy and nephropathy. Biochemistry, immunohistochemistry, and in situ hybridization showed that the depletion of mtDNA in muscle fibers was correlated with a respiratory chain defect and with lack of mitochondrially translated proteins. Although the differential tissue involvement in these infants suggests mtDNA heteroplasmy, sequence analysis of mtDNA replication origins did not reveal any abnormality that could account for the low copy number.

The mec -4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration

Abstract: Three dominant mutations of mec-4, a gene needed for mechanosensation, cause the touch-receptor neurons of Caenorhabditis elegans to degenerate. With deg-1, another C. elegans gene that can mutate to induce neuronal degeneration and that is similar in sequence, mec-4 defines a new gene family. Cross-hybridizing sequences are detectable in other species, raising the possibility that degenerative conditions in other organisms may be caused by mutations in similar genes. All three dominant mec-4 mutations affect the same amino acid. Effects of amino-acid substitutions at this position suggest that steric hindrance may induce the degenerative state.