Biomedical subjects

J P Greenberg

Publications and source records attributed to J P Greenberg.

At least 19 recordsLinked to original sources

PubMed2001

Middle cerebral artery flow velocity correlates with common carotid artery volume flow rate after CO2 inhalation.

Cerebral vasoreactivity can be studied with transcranial Doppler (TCD) by monitoring CO2-induced middle cerebral artery (MCA) velocity changes. Expected MCA mean velocity (Vm) changes due to changes in end-expiratory CO2 (EE-CO2) are established, but reactivity of common carotid artery (CCA) volume flow rate (VFR) has not been extensively reported. The authors assess the relationship between MCA Vm, CCA VFR, and EE-CO2. Ten normal individuals without cerebrovascular disease and with CCA diameters of more than 3.0 mm were studied. CCA VFR was obtained by Color Velocity Imaging Quantification and Ipsilateral MCA Vm by standard TCD methods. Each side was studied before, during, and after inhalation of 5% CO2. EE-CO2, blood pressure, and pulse rate were monitored. Four women and 6 men with mean age of 36 years were included. Significant correlations between MCA Vm and EE-CO2, CCA VFR and EE-CO2, and MCA Vm and CCA VFR were found. MCA Vm and CCA VFR increased 5.2% and 4.3% per mm Hg increase in EE-CO2, respectively. MCA Vm increased 0.3 cm/s for each ml/min increase in CCA VFR. In normal individuals, there is a direct correlation between MCA Vm, CCA VFR, and EE-CO2. Measurement of CCA VFR changes during CO2 inhalation may be an alternative method to estimate cerebral vasoreactivity when the MCA velocity cannot be obtained because of inadequate acoustic temporal windows.

Administration, Inhalation↗

PubMed2000

Enzymatic synthesis of methylbutenol from dimethylallyl diphosphate in needles of Pinus sabiniana.

Methylbutenol (2-methyl-3-buten-2-ol) is an abundant volatile organic compound released from Western U.S. pines. To understand the mechanism of methylbutenol formation, we developed a sensitive gas chromatographic assay for its detection and determined that needles of gray pine (Pinus sabiniana) contain an enzyme that catalyzes the synthesis of methylbutenol from dimethylallyl diphosphate (DMAPP). The methylbutenol synthase activity was partially purified; its pH optimum was 7-8, and, like other prenyl diphosphate utilizing enzymes, it was dependent on the presence of a divalent cation, preferably Mn2+. The enzyme also required K+ or NH4+ for activity. The Km values for DMAPP and Mn2+ were about 4.8 and 6 mM, respectively. Geranyl diphosphate was not a substrate for the enzyme, so it is distinct from linalool synthase, a plant enzyme that catalyzes an analogous reaction. The methylbutenol synthase reaction may be responsible for the majority of light-dependent methylbutenol production by many pine species in the Western United States.

Butanols↗

PubMed1999

600 ps molecular dynamics reveals stable substructures and flexible hinge points in cAMP dependent protein kinase.

Molecular dynamics simulations of the catalytic subunit of cAMP dependent protein kinase (cAPK) have been performed in an aqueous environment. The relations among the protein hydrogen-bonding network, secondary structural elements, and the internal motions of rigid domains were examined. The values of fluctuations of protein dihedral angles during dynamics show quite distinct maxima in the regions of loops and minima in the regions of alpha-helices and beta-strands. Analyses of conformation snapshots throughout the run show stable subdomains and indicate that these rigid domains are constrained during the dynamics by a stable network of hydrogen bonds. The most stable subdomain during the dynamics was in the small lobe including part of the carboxy-terminal tail. The most significant flexible region was the highly conserved glycine-rich loop between beta strands 1 and 2 in the small lobe. Many of the main chain dihedral angle changes measured in a comparison of the crystallographic structures of "open" and "closed" conformations of cAPK correspond to the highly flexible residues found during dynamics.

Animals↗

PubMed1998

Co-registration of cortical magnetic stimulation and functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) are noninvasive techniques recently used to investigate cortical motor physiology. However, these modalities measure different phenomena, and in studies of human motor control they have given inconsistent results. We have developed a reproducible technique which co-registers TMS and fMRI, using a frameless method. In four normal subjects, the TMS map and fMRI activation were present on the primary motor cortex contralateral to the target hand, with some extension into primary sensory cortex. fMRI activation alone was also present in the medial motor cortex bilaterally and in the sensorimotor cortex ipsilateral to the target hand. This technique allows a more comprehensive evaluation of the physiologic events involved in motor control.

Adult↗

PubMed1998

Psychopharmacologic treatment of acquired attention disorders in children with brain injury.

This investigation examined the efficacy of psychostimulant therapy in alleviating neurobehavioral dysfunction attendant to pediatric brain injury. The most commonly reported neurobehavioral sequelae associated with head injury in the pediatric population involve deficits along the attentional matrix. This is also the most common objectively documented neurobehavioral finding among children as well as adults. There are several investigations in the adult literature which have employed the use of psychostimulants in treating both psychiatric and neuropsychological residua associated with head injury. Overall, the results of these studies are equivocal, but suggest a beneficial impact on general functioning. The present prospective investigation utilized a double-blind, placebo-controlled, cross-over experimental design to examine the efficacy of methylphenidate in treating children with acquired attentional disorders secondary to brain injury. A cohort of 14 children with varying degrees of head injury were recruited for participation. As expected, differences between drug and placebo conditions uniformly achieved statistical significance. Additionally, there were no differences in performance between baseline and placebo conditions on neurobehavioral tasks of attention and concentration. Current findings suggest that methylphenidate (and probably other psychostimulants such as Cylert, Adderal, Wellbutrin and dextroamphetamine sulfate) is an extremely effective agent in treating attentional disorders secondary to brain injury in children.

Adolescent↗

PubMed1996

MDMovie: a molecular dynamics viewing tool.

The graphics program MDMovie (Molecular Dynamics Movie), written in C using IRIS GL graphics library calls, is designed to facilitate the visualization and interpretation of empirical force field data. MDMovie was created and initially adapted in accord with the needs of physical chemists and thereafter became an expandable analysis tool. Capabilities include the display of chemical structure, animation of molecular dynamics and Monte Carlo trajectories, and the visual representation of various vector and scalar dynamical properties. In addition to being a research tool, MDMovie has features for creating presentation videos and hardcopy output. A library is also available for linking to Fortran simulation codes running on a remote machine and connecting to MDMovie via a socket connection. MDMovie continues to be an ongoing research project and new features are actively being added in collaboration with various research groups. Future plans include porting to OpenGL and the design of an XII-based user interface.

Computer Graphics↗

PubMed1995

QMView: a computational chemistry three-dimensional visualization tool at the interface between molecules and mankind.

QMView is designed to facilitate the visualization and interpretation of quantum mechanical data. Capabilities include display of chemical structure, animation of quantum mechanically determined vibrational modes, and depiction of electronic properties and three-dimensional molecular orbitals. QMView has a user-friendly interface that allows users to interactively manipulate many features of the molecular structure and/or property, including positioning and structure representation, via mouse-activated dialog boxes. Although the interface allows input from results of any of the popularly used quantum mechanical software, we have focused on GAMESS, a widely distributed quantum chemistry code. QMView has been designed with the special feature of working in distributed mode with GAMESS, the latter running on a supercomputer, the former running on a Silicon Graphics platform. Ancillary programs provide a method of obtaining output of graphic images in various media, including hardcopy, PostScript files, slide, and/or video. These and other original features discussed in this article provide a graphic interface that is unique compared to others that are currently available. Examples of images produced by QMView are presented.

Computer Graphics↗

PubMed1994

On higher buckling transitions in supercoiled DNA.

A combination of detailed energy minimization and molecular dynamics studies of closed circular DNA offers here new information that may be relevant to the dynamics of short DNA chains and/or low superhelical densities. We find a complex dependence of supercoiled DNA energies and geometries on the linking number difference delta Lk as physiological superhelical densities (magnitude of sigma approximately 0.06) are approached. The energy minimization results confirm and extend predictions of classical elasticity theory for the equilibria of elastic rods. The molecular dynamics results suggest how these findings may affect the dynamics of supercoiled DNA. The minimization reveals sudden higher order configurational transitions in addition to the well-known catastrophic buckling from the circle to the figure-8. The competition among the bending, twisting, and self-contact forces leads to different families of supercoiled forms. Some of those families begin with configurations of near-zero twist. This offers the intriguing possibility that nicked DNA may relax to low-twist forms other than the circle, as generally assumed. Furthermore, for certain values of delta Lk, more than one interwound DNA minimum exists. The writhing number as a function of delta Lk is discontinuous in some ranges; it exhibits pronounced jumps as delta Lk is increased from zero, and it appears to level off to a characteristic slope only at higher values of delta Lk. These findings suggest that supercoiled DNA may undergo systematic rapid interconversions between different minima that are both close in energy and geometry. Our molecular dynamics simulations reveal such transitional behavior. We observe the macroscopic bending and twisting fluctuations of interwound forms about the global helix axis as well as the end-over-end tumbling of the DNA as a rigid body. The overall mobility can be related to magnitude of sigma and to the bending, twisting, and van der Waals energy fluctuations. The general character of molecular motions is thus determined by the types of energy minima found at a given delta Lk. Different time scales may be attributed to each type of motion: The overall chain folding occurs on a time scale almost an order of magnitude faster than the end-over-end tumbling. The local bending and twisting of individual chain residues occur at an even faster rate, which in turn correspond to several cycles of local variations for each large-scale bending and straightening motion of the DNA.

DNA, Superhelical↗

PubMed1991

Structures of the (+)- and (-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyre ne adducts to guanine-N2 in a duplex dodecamer.

The structures of the mirror image (+)- and (-)-trans-anti-adducts of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene to guanine N2 have been of great interest because the high biological activity of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene in mammalian mutagenesis and tumorigenesis has been attributed to the predominant (+)-trans-anti-adduct. We have carried out new potential energy minimization studies, involving wide-scale conformational searches on small modified DNA subunits, followed by energy-minimized build-up techniques, to generate atomic resolution views of these adducts. These energy-minimized duplex dodecamers were then subjected to 100-ps molecular dynamic simulations with solvent and salt to yield animated molecular structures. The most favored computed structure for the (+)-adduct places the pyrenyl moiety in the B-DNA minor groove, with its long axis directed toward the 5' end of the modified strand, and with a pronounced bend in the helix axis. In the (-)-adduct, there are 2 favored structures. One places the pyrenyl moiety in the minor groove, whereas the other positions it in the major groove; in both cases, the pyrenyl long axis is directed more toward the 3' end of the modified strand, and with much less helix axis bend. Structures with intercalation character computed for these adducts are less preferred. The favored computed structures agree with spectroscopic data on the (+)- and (-)-trans-anti-adducts, whereas recent experimental evidence suggests that cis-adducts assume intercalation-type structures. Perhaps the conformational distinctions elucidated for the (+)- and (-)-trans anti-adducts play a role in their differential tumorigenic properties in mammalian systems.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1990

Caudate infarcts.

Eighteen patients had caudate nucleus infarcts (10 left-sided; 8 right-sided). Infarcts extended into the anterior limb of the internal capsule in 9 patients, and also the anterior putamen in 5 patients. Thirteen patients had motor signs, most often a slight transient hemiparesis. Dysarthria was common (11 patients). Cognitive and behavioral abnormalities were frequent, and included abulia (10 patients), agitation and hyperactivity (7 patients), contralateral neglect (3 patients, all right caudate), and language abnormalities (2 patients, both left caudate). The majority of patients had risk factors for penetrating artery disease. Branch occlusion of Heubner's artery, or perforators from the proximal anterior or middle cerebral arteries were the posited mechanism of infarction.

Adult↗

PubMed1985

Effects of plasmin on rabbit platelets.

The effects of plasmin have been examined because platelets may be exposed to plasmin in vivo and treatment of platelets with plasmin shortens platelet survival. Rabbit plasmin was prepared by urokinase activation of plasminogen immobilized on lysine-Sepharose. Plasmin caused rabbit platelets to aggregate and release the contents of their amine storage granules, but aggregation was slower than in response to ADP or thrombin. EDTA, prostaglandin E1, or creatine phosphate/creatine phosphokinase were inhibitory, but indomethacin was not. Deaggregation did not occur when platelets had been aggregated by a concentration of plasmin that caused extensive release of granule contents. EDTA or prostaglandin E1 caused deaggregation. Low concentrations of ADP and plasmin acted synergistically in causing platelet aggregation. Plasmin decreased the amounts of platelet membrane glycoproteins that stained with periodic acid-Schiff reagent; glycoprotein I was more susceptible than glycoprotein II and III. Concentrations of plasmin that induced the release of amine storage granule contents also released PAS-staining granule glycoproteins. Platelets incubated with plasmin, washed and resuspended, were not aggregated by ADP, but were aggregated strongly by the combination of fibrinogen and ADP, and bound 125I-fibrinogen to a greater extent than untreated platelets. Platelets preincubated with a high concentration of plasmin were unresponsive to thrombin, but were sometimes aggregated by fibrinogen. Plasmin decreased the buoyant density and increased the median size of platelets. Thus plasmin, as well as ADP and thrombin, may contribute to the density shift observed in platelets from rabbits in which thrombosis and continuous vessel injury have been induced.

Adenosine Diphosphate↗

PubMed1984