Showing papers by "Stony Brook University published in 1991"

Survival in Patients with Primary Pulmonary Hypertension: Results from a National Prospective Registry

Abstract: Objective To characterize mortality in persons diagnosed with primary pulmonary hypertension and to investigate factors associated with survival. Design Registry with prospective follow-up. Setting Thirty-two clinical centers in the United States participating in the Patient Registry for the Characterization of Primary Pulmonary Hypertension supported by the National Heart, Lung, and Blood Institute. Patients Patients (194) diagnosed at clinical centers between 1 July 1981 and 31 December 1985 and followed through 8 August 1988. Measurements At diagnosis, measurements of hemodynamic variables, pulmonary function, and gas exchange variables were taken in addition to information on demographic variables, medical history, and life-style. Patients were followed for survival at 6-month intervals. Main results The estimated median survival of these patients was 2.8 years (95% Cl, 1.9 to 3.7 years). Estimated single-year survival rates were as follows: at 1 year, 68% (Cl, 61% to 75%); at 3 years, 48% (Cl, 41% to 55%); and at 5 years, 34% (Cl, 24% to 44%). Variables associated with poor survival included a New York Heart Association (NYHA) functional class of III or IV, presence of Raynaud phenomenon, elevated mean right atrial pressure, elevated mean pulmonary artery pressure, decreased cardiac index, and decreased diffusing capacity for carbon monoxide (DLCO). Drug therapy at entry or discharge was not associated with survival duration. Conclusions Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables: mean pulmonary artery pressure, mean right atrial pressure, and cardiac index. Such an equation, once validated prospectively, could be used as an adjunct in planning treatment strategies and allocating medical resources.

Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG.

Abstract: Oxidative damage to DNA, reflected in the formation of 8-oxo-7-hydrodeoxyguanosine (8-oxodG), may be important in mutagenesis, carcinogenesis and the ageing process. Kuchino et al. studied DNA synthesis on oligodeoxynucleotide templates containing 8-oxodG, concluding that the modified base lacked base pairing specificity and directed misreading of pyrimidine residues neighbouring the lesion. Here we report different results, using an approach in which the several products of a DNA polymerase reaction can be measured. In contrast to the earlier report, we find that dCMP and dAMP are incorporated selectively opposite 8-oxodG with transient inhibition of chain extension occurring 3' to the modified base. The potentially mutagenic insertion of dAMP is targeted exclusively to the site of the lesion. The ratio of dCMP to dAMP incorporated varies, depending on the DNA polymerase involved. Chain extension from the dA.8-oxodG pair was efficiently catalysed by all polymerases tested.

Effect of Oral Milrinone on Mortality in Severe Chronic Heart Failure

Abstract: Background. Milrinone, a phosphodiesterase inhibitor, enhances cardiac contractility by increasing intracellular levels of cyclic AMP, but the long-term effect of this type of positive inotropic agent on the survival of patients with chronic heart failure has not been determined. Methods. We randomly assigned 1088 patients with severe chronic heart failure (New York Heart Association class III or IV) and advanced left ventricular dysfunction to double-blind treatment with 40 mg of oral milrinone daily (561 patients) or placebo (527 patients). In addition, all patients received conventional therapy with digoxin, diuretics, and a converting-enzyme inhibitor throughout the trial. The median period of follow-up was 6.1 months (range, 1 day to 20 months). Results. As compared with placebo, milrinone therapy was associated with a 28 percent increase in mortality from all causes (95 percent confidence interval, 1 to 61 percent; P = 0.038) and a 34 percent increase in cardiovascular mortality (95 percent...

Subjective probability and delay.

Abstract: Human subjects indicated their preference between a hypothetical $1,000 reward available with various probabilities or delays and a certain reward of variable amount available immediately. The function relating the amount of the certain-immediate reward subjectively equivalent to the delayed $1,000 reward had the same general shape (hyperbolic) as the function found by Mazur (1987) to describe pigeons' delay discounting. The function relating the certain-immediate amount of money subjectively equivalent to the probabilistic $1,000 reward was also hyperbolic, provided that the stated probability was transformed to odds against winning. In a second experiment, when human subjects chose between a delayed $1,000 reward and a probabilistic $1,000 reward, delay was proportional to the same odds-against transformation of the probability to which it was subjectively equivalent.

Scaling effective Lagrangians in a dense medium.

Abstract: By using effective chiral Lagrangians with a suitable incorporation of the scaling property of QCD, we establish the approximate in-medium scaling law, ${\mathit{m}}_{\mathrm{\ensuremath{\sigma}}}^{\mathrm{*}}$/${\mathit{m}}_{\mathrm{\ensuremath{\sigma}}}$\ensuremath{\approxeq}${\mathit{m}}_{\mathrm{N}}^{\mathrm{*}}$/${\mathit{m}}_{\mathrm{N}}$ \ensuremath{\approxeq}${\mathit{m}}_{\mathrm{\ensuremath{\rho}}}^{\mathrm{*}}$/${\mathit{m}}_{\mathrm{\ensuremath{\rho}}}$\ensuremath{\approxeq}${\mathit{m}}_{\mathrm{\ensuremath{\omega}}}^{\mathrm{*}}$/${\mathit{m}}_{\mathrm{\ensuremath{\omega}}}$\ensuremath{\approxeq}${\mathit{f}}_{\mathrm{\ensuremath{\pi}}}^{\mathrm{*}}$/${\mathit{f}}_{\mathrm{\ensuremath{\pi}}}$. This has a highly nontrivial implication for nuclear processes at and above nuclear-matter density. Some concrete cases are cited in this paper.

The Dawn of Darwinian Medicine

Abstract: While evolution by natural selection has long been a foundation for biomedical science, it has recently gained new power to explain many aspects of disease. This progress results largely from the disciplined application of what has been called the adaptations program. We show that this increasingly significant research paradigm can predict otherwise unsuspected facets of human biology, and that it provides new insights into the causes of medical disorders, such as those discussed below: 1. Infection. Signs and symptoms of the host-parasite contest can be categorized according to whether they represent adaptations or costs for host or parasite. Some host adaptations may have contributed to fitness in the Stone Age but are obsolete today. Others, such as fever and iron sequestration, have been incorrectly considered harmful. Pathogens, with their large populations and many generations in a single host, can evolve very rapidly. Acquisition of resistance to antibiotics is one example. Another is the recently demonstrated tendency to change virulence levels in predictable ways in response to changed conditions imposed incidentally by human activities. 2. Injuries and toxins. Mechanical injuries or stressful wear and tear are conceptually simpler than infectious diseases because they are not contests between conflicting interests. Plant-herbivore contests may often underlie chemical injury from the defensive secondary compounds of plant tissues. Nausea in pregnancy, and allergy, may be adaptations against such toxins. 3. Genetic factors. Common genetic diseases often result from genes maintained by other beneficial effects in historically normal environments. The diseases of aging are especially likely to be associated with early benefits. 4. Abnormal environments. Human biology is designed for Stone Age conditions. Modern environments may cause many diseases-for example, deficiency syndromes such as scurvy and rickets, the effects of excess consumption of normally scarce nutrients such as fat and salt, developmental diseases such as myopia, and psychological reactions to novel environments. The substantial benefits of evolutionary studies of disease will be realized only if they become central to medical curricula, an advance that may at first require the establishment of one or more research centers dedicated to the further development of Darwinian medicine.

Direct URCA process in neutron stars.

Abstract: We show that the direct URCA process can occur in neutron stars if the proton concentration exceeds some critical value in the range 11--15%. The proton concentration, which is determined by the poorly known symmetry energy of matter above nuclear density, exceeds the critical value in many current calculations. If it occurs, the direct URCA process enhances neutrino emission and neutron star cooling rates by a large factor compared to any process considered previously.

Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs.

Abstract: Tetracyclines have long been considered useful adjuncts in peridontal therapy based on their antimicrobial efficacy against putative periodontopathogens. However, recently these drugs were found to inhibit mammalian collagenases and several other matrix metalloproteinases (MMPs) by a mechanism independent of their antimicrobial activity. Evidence is presented that this property may be therapeutically useful in retarding pathologic connective tissue breakdown, including bone resorption. The experiments leading to this discovery are described and possible mechanisms are addressed, including the specificity of tetracyclines' anti-collagenase activity, the role of the drugs' metal ion (Zn2+, Ca2+)- binding capacity, and the site on the tetracycline molecule responsible for this nonantimicrobial property. Of extreme interest, the tetracycline molecule has been chemically modified in multiple ways, generating a new family of compounds called CMTs (chemically modified tetracyclines) that lack antimicrobial but s...

Changes in brain glucose metabolism in cocaine dependence and withdrawal.

Abstract: Objective The authors investigated changes in brain function associated with cocaine dependence and withdrawal to provide clues regarding the processes that lead to the uncontrollable self-administration of cocaine. Method They measured regional brain metabolism with [18F]-fluorodeoxyglucose (FDG) and positron emission tomography in 15 outpatients with the diagnosis of cocaine abuse and 17 normal comparison subjects. Ten of the patients were studied less than 1 week after they had last had cocaine, and five were studied 2-4 weeks after withdrawal. Results Patients studied within 1 week of cocaine withdrawal but not those studied within 2-4 weeks of cocaine withdrawal had higher levels of global brain metabolism as well as higher levels of regional brain metabolism in the basal ganglia and orbitofrontal cortex than did normal subjects, probably as a consequence of less brain dopamine activity. There was also a significant relationship between the number of days since cocaine withdrawal and regional brain glucose metabolism in the orbitofrontal cortex and in the basal ganglia, and the correlations between cocaine craving and metabolic activity were significant in the prefrontal cortex and the orbitofrontal cortex. Conclusions Although the time-dependent fall in metabolic activity suggests that the higher metabolic activity observed less than a week after cocaine withdrawal may represent a nonspecific expression of drug withdrawal, the selectivity of changes in glucose metabolism for the basal ganglia and for the orbitofrontal cortex suggests that the regional metabolic changes seen in cocaine abusers during detoxification are related to changes in brain dopamine activity.

Volume Visualization

Abstract: Volume visualization is a method of extracting information from volumetric datasets through interactive graphics and imaging, and is concerned with the representation, manipulation, and rendering of these datasets [Gallagher 1995; Kaufman 1991; Rosenblum 1994]. Volume data are 3D entities that may have information inside them, may not consist of surfaces and edges, or may be too voluminous to be represented geometrically. Volume visualization encompasses an array of techniques for peering inside the dataset and for interactively extracting meaningful information from it using transformations, cuts, segmentation, translucency, measurements, and the like. The primary sources of volume data are three: sampled data of real objects or phenomena, computed data produced by a computer simulation, and modeled data generated from a geometric model. Examples of applications generating sampled data are medical imaging (e.g., CT, MRI), biology (e.g., confocal microscopy), geoscience (e.g., seismic measurements), industry (e.g., nondestructive inspection), and chemistry (e.g., electron density maps) [Kaufman 1991]. Some examples of applications generating computed datasets, typically by running a simulation on a supercomputer, are meteorology (e.g., storm prediction), computational fluid dynamics (e.g., water flow), and materials science (e.g., new materials). Recently, many traditional computer graphics applications, such as computer-aided design and flight simulation [Cohen and Shaked 1993; Kaufman et al. 1993], have been exploiting the advantages of volumetric techniques for modeling, manipulation, and visualization, an approach called volume graphics [Kaufman et al. 1993]. Volumetric data is typically a set S of samples (x, y, z, v), representing the value v of some property of the data at a 3D location (x, y, z). If v is simply a 0 or a 1, with 0 indicating background and 1 indicating the object, the data is called binary data. The data may instead be multivalued, with v representing some measurable property of the data, such as density, color, heat, or pressure. The value v may even be a vector, representing, for example, velocity at each location. In general, the samples may be taken at random locations in space, but in many cases S is isotropic, containing samples taken at regularly spaced intervals along three orthogonal axes. Since S is defined on a regular grid, a 3D array (called volume buffer, cubic frame buffer, 3D raster) is typically used to store the values. S is therefore referred to as the array of values S(x, y, z), which is defined only at grid locations. A function may be defined to describe the value at any continuous location by approximating v at a location (x, y, z) using some interpolation function to S, such as zero-order (nearest-neighbor), piecewise function known as first-order (trilinear), or higher-order interpolation. The region of constant value that surrounds each sample in zero-order interpolation is known as a volume cell (voxel for short), with each voxel being a rectangular cuboid having six faces, twelve edges, and eight corners. The terms, voxel, grid location,

Functional communication training to reduce challenging behavior: maintenance and application in new settings

Abstract: We evaluated the initial effectiveness, maintenance, and transferability of the results of functional communication training as an intervention for the challenging behaviors exhibited by 3 students. Assessment indicated that escape from academic demands was involved in the maintenance of the challenging behaviors. Social attention was also implicated as controlling the behavior of 1 student. The intervention involved teaching alternative assistance-seeking and attention-getting phrases to the students in an effort to replace challenging behavior with these verbal equivalents. Multiple baseline data collected across the 3 students indicated that not only did the intervention substantially reduce challenging behavior but also that these results transferred across new tasks, environments, and teachers, and were generally maintained from 18 to 24 months following the introduction of functional communication training. These results are discussed in light of recent efforts to develop effective interventions for severe challenging behavior and to understand the processes underlying transfer and maintenance of intervention effects.

Cell-free, de novo synthesis of poliovirus

Abstract: Cell-free translation of poliovirus RNA in an extract of uninfected human (HeLa) cells yielded viral proteins through proteolysis of the polyprotein. In the extract, newly synthesized proteins catalyzed poliovirus-specific RNA synthesis, and formed infectious poliovirus de novo. Newly formed virions were neutralized by type-specific antiserum, and infection of human cells with them was prevented by poliovirus receptor-specific antibodies. Poliovirus synthesis was increased nearly 70-fold when nucleoside triphosphates were added, but it was abolished in the presence of inhibitors of translation or viral genome replication. The ability to conduct cell-free synthesis of poliovirus will aid in the study of picornavirus proliferation and in the search for the control of picornaviral disease.

Eyelid movements : mechanisms and normal data

Abstract: This study provides a comprehensive description of upper eyelid movement in normal human subjects. Using the magnetic search coil technique to monitor lid position and modified skin electrodes to record orbicularis oculi electromyographic (EMG) activity, the authors found that the basic eyelid movements, blinks, and saccadic lid movements, can be uniquely and reliably characterized by their amplitude-maximum velocity relationships. The data show that similar increases in levator palpebrae activity produce the upward lid movements that accompany upward saccadic eye movements as well as the upward phase of a blink. The lid movements that accompany downward saccadic eye movements arise almost exclusively from the passive downward forces and relaxation of the levator palpebrae muscle. In contrast, active orbicularis oculi contraction and the passive downward forces act together to generate lid closure with a blink. These normative data and techniques provide the basis for the clinical analysis of lid motility by which abnormal lid movements can be compared with normal lid kinematics.

The effects of severe behavior problems in children on the teaching behavior of adults.

Abstract: Applied behavior analysts have focused on how adults can influence the problem behavior of children using a variety of behavior modification strategies. A related question, virtually unexplored, is how the behavior problems of children influence adults. This child-effects concept was explored empirically in a study involving 12 adults who were asked to teach four pairs of children in which one member of the pair exhibited problem behavior and the other typically did not. Results demonstrated that problem children displayed tantrums, aggression, and self-injury contingent on adult instructional attempts but not at other times, whereas nonproblem children showed little or no problem behavior at any time. Importantly, from a child-effects perspective, adults engaged in teaching activities with nonproblem children more often than with problem children. Also, when an adult worked with a problem child, the breadth of instruction was more limited and typically involved those tasks associated with lower rates of behavior problems. The implications of these results are discussed with respect to theories of escape behavior, current assessment practices, and intervention issues related to maintenance. The existence of child effects suggests that problem behavior may be better understood when it is conceptualized as involving a process of reciprocal influence between adult and child.

HIV-associated disease of the nervous system: review of nomenclature and proposal for neuropathology-based terminology.

Abstract: Herbert Budka 1, Clayton A. Wiley 2, Paul Kleihues 3, Juan Artigas 4, Arthur K. Asbury 5, Eun-Sook Cho 6, David R. Cornblath 7, Mauro C. Dal Canto 8, Umberto DeGirolami 9, Dennis Dickson 10, Leon G. Epstein 11, Margaret M. Esiri 12, Felice Giangaspero 13, Georg Gosztonyi 14, Francoise Gray 15, John W. Griffin 7, Dominique Henin 16, Yuzo lwasaki 17, Robert S. Janssen '8, Richard T. Johnson 7, Peter L. Lantos 19, William D. Lyman 10, Justin C. McArthur 7, Kazuo Nagashima 20, Nancy Peress 21, Carol K. Petito 22, Richard W. Price 23, Roy H. Rhodes Z4, Marc Rosenblum 25, Gerard Said 26, Francesco Scaravilli 27, Leroy R. Sharer 6, Harry V. Vinters 28

Site-specific mutagenesis using a gapped duplex vector: A study of translesion synthesis past 8-oxodeoxyguanosine in E. coli

Abstract: We have constructed a gapped plasmid vector in which a single defined lesion is introduced, site-specifically, within a single-strand region. Efficiency of translesional synthesis is determined by the number of colonies recovered following transformation of E. coli. The nucleotide sequence of progeny plasmids in the gapped region of the vector reflects incorporation of bases opposite and near the lesion. The analysis detects non-mutagenic as well as mutagenic events. This system was used to establish the mutagenic potential of 2'-deoxy-7,8-dihydro-8-oxoguanosine (8-oxodG), a lesion produced by the action of active oxygen species on DNA. The presence of 8-oxodG did not affect the number of transformants recovered. Most transformants (greater than 99%) contained G:C pairs at the site of the lesion; however, a limited number of targeted G----T transversions were observed in the presence and absence of SOS induction. Base substitutions neighboring the lesion, reported for an in vitro system, were not observed. We conclude that the 8-oxodG lesion in DNA is weakly mutagenic in E. coli.

Impact of carnivore ravaging on zooarchaeological measures of element abundance

Abstract: Most zooarchaeologists estimate limb-bone abundance from limb ends. Researchers have provided detailed documentation of the preferential destruction by carnivores of limb ends (Binford 1981; Binford et al. 1988; Blumenschine 1988; Brain 1981; Marean et al. 1990; Orloff and Marean 1990; Sutcliffe 1970). Others have observed differences between limb abundances calculated on limb shafts vs. ends, suggesting shaft pieces may provide more accurate estimates of original element abundance in carnivore-ravaged assemblages (Bunn 1986; Bunn and Kroll 1986; Blumenschine 1988; Klein 1975; Marean et al. 1990; Orloff and Marean 1990). However, the exact quantitative effect of carnivore ravaging on measures of element abundance has never been investigated. We provide an experimental test of the accuracy of different bone portions for estimating the original element abundance after carnivore ravaging. Spotted hyenas were allowed to ravage 33 simulated archaeological sites of known element abundance. Estimates of abundance calculated on limb ends differ greatly from original bone abundance, and estimates based on proximal/distal-shaft pieces are also inaccurate. Estimates from middle-shaft fragments, however, are uniquely accurate. These experimental data mandate reanalysis of assemblages where limb frequencies were calculated from limb ends and carnivore ravaging is implicated, and experimentally vindicate observations originally provided by Klein (1975).

Measuring daily events and experiences: decisions for the researcher.

Abstract: There has been a burgeoning interest in studying daily events and experiences. This article discusses a variety of methodologic challenges that face daily event and experience researchers. The issues discussed include techniques for measuring events, the development of event checklists, sampling event content, specifying event appraisals, event validation procedures, and the creation of summary measures derived from event checklists. Procedural issues discussed include determining the number of observations and persons needed for daily event studies, the evaluation of response, attrition, and missing item bias, and problems linking event reports over time.

Symplectic manifolds with contact type boundaries

Abstract: An example of a 4-dimensional symplectic manifold with disconnected boundary of contact type is constructed. A collection of other results about symplectic manifolds with contact-type boundaries are derived using the theory ofJ-holomorphic spheres. In particular, the following theorem of Eliashberg-Floer-McDuff is proved: if a neighbourhood of the boundary of (V, ω) is symplectomorphic to a neighbourhood ofS2n−1 in standard Euclidean space, and if ω vanishes on all 2-spheres inV, thenV is diffeomorphic to the ballB2n.

Marital adjustment, parental disagreements about child rearing, and behavior problems in boys: Increasing the specificity of the marital assessment.

Abstract: 2 studies were conducted to illustrate how measuring a specific aspect of marriage, namely, child-rearing disagreements, provides a better understanding of the link between marriage and boys' behavior. In Study 1, 200 mothers of 3-year-old boys completed unstandardized measures of marital functioning and child behavior. An index of child-rearing disagreements: (1) correlated with a greater variety of behavior problems than nonchild disagreements, and (2) improved upon the prediction of behavior problems after accounting for nonchild disagreements as well as after accounting for boys' exposure to marital conflict. In Study 2, 87 mothers with 4-6-year-old sons completed the index of child-rearing disagreements used in Study 1 as well as standard measures of marital functioning and child behavior. Child-rearing disagreements: (1) predicted a greater variety of behavior problems than global marital adjustment, and (2) improved upon the prediction of internalizing problems after controlling for global marital adjustment as well as after controlling for boys' exposure to marital conflict.

Dimuon production in proton-copper collisions at sqrt s =38.8 GeV.

Abstract: Experimental results on the production of dimuons by 800-GeV protons incident on a copper target are presented. The results include measurements of both the continuum of dimuons and the dimuon decays of the three lowest-mass $\ensuremath{\Upsilon}$ $S$ states. A description of the apparatus, data acquisition, and analysis techniques is included. A comparison of the results with data taken at lower incident energies indicates a scaling behavior of the continuum dimuon yields.