Biomedical subjects

D R Nelson

Publications and source records attributed to D R Nelson.

At least 19 recordsLinked to original sources

PubMed2006

The genome of black cottonwood, Populus trichocarpa (Torr. & Gray).

We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.

Arabidopsis↗

PubMed2006

Nematic textures in spherical shells.

The equilibrium texture of nematic shells is studied as a function of their thickness. For ultrathin shells the ground state has four short 1/2 disclination lines but, as the thickness of the film increases, a three-dimensional escaped configuration composed of two pairs of half-hedgehogs becomes energetically favorable. We derive an exact solution for the nematic ground state in the one Frank constant approximation and study the stability of the corresponding texture against thermal fluctuations.

Journal Article↗

PubMed2006

Crystallography on curved surfaces.

We study static and dynamical properties that distinguish 2D crystals constrained to lie on a curved substrate from their flat-space counterparts. A generic mechanism of dislocation unbinding in the presence of varying Gaussian curvature is presented in the context of a model surface amenable to full analytical treatment. We find that glide diffusion of isolated dislocations is suppressed by a binding potential of purely geometrical origin. Finally, the energetics and biased diffusion dynamics of point defects such as vacancies and interstitials are explained in terms of their geometric potential.

Crystallography↗

PubMed2005

Pause point spectra in DNA constant-force unzipping.

Under constant applied force, the separation of double-stranded DNA into two single strands is known to proceed through a series of pauses and jumps. Given experimental traces of constant-force unzipping, we present a method whereby the locations of pause points can be extracted in the form of a pause point spectrum. A simple theoretical model of DNA constant-force unzipping is presented, which generates theoretical pause point spectra through Monte Carlo simulation of the unzipping process. The locations of peaks in the experimental and theoretical pause point spectra are found to be nearly coincident below 6000 basepairs for unzipping the bacteriophage lambda-genome. The model only requires the sequence, temperature, and a set of empirical basepair binding and stacking energy parameters, and the good agreement with experiment suggests that pause point locations are primarily determined by the DNA sequence. The model is also used to predict pause point spectra for the bacteriophage phi X174 genome. The algorithm for extracting the pause point spectrum might also be useful for studying related systems which exhibit pausing behavior such as molecular motors.

Algorithms↗

PubMed2003

Grain boundary scars and spherical crystallography.

We describe experimental investigations of the structure of two-dimensional spherical crystals. The crystals, formed by beads self-assembled on water droplets in oil, serve as model systems for exploring very general theories about the minimum-energy configurations of particles with arbitrary repulsive interactions on curved surfaces. Above a critical system size we find that crystals develop distinctive high-angle grain boundaries, or scars, not found in planar crystals. The number of excess defects in a scar is shown to grow linearly with the dimensionless system size. The observed slope is expected to be universal, independent of the microscopic potential.

Journal Article↗

PubMed2003

Survival and resource utilization in liver transplant recipients: the impact of admission to the intensive care unit.

The organ allocation system for liver transplantation was recently changed to address criticisms that it was too subjective and relied too heavily on total waiting time. The new system, Model for End-Stage Liver Disease and Pediatric Model for End-Stage Liver Disease (MELD/PELD), stratifies patients based on the risk of 3-month pretransplant mortality, allocating livers thereby. There is concern that such a scheme gives priority to the sickest patients, who may not enjoy good posttransplant outcomes. The aim of the present study was to compare the outcomes of liver transplant recipients who had been admitted to the intensive care unit (ICU) to those who had not. Admission to the ICU is considered here to be another indicator of the severity of illness. Patients who underwent liver transplantation at the Cleveland Clinic between January 1, 1993 and October 31, 1998 and were at least 18 years of age were coded for liver transplantation as status 2, 2A, and 2B (n = 112). These patients fell into three groups: those who had been admitted to an ICU before transplantation (group A, n = 16), those who had been admitted to the hospital but not to an ICU (group B, n = 63), and those who were living at home and had undergone an elective transplant (group C, n = 33). Clinical and demographic information (age, sex, race, disease severity, disease etiology, and cold ischemia time) were associated with patient survival, patient/graft survival, and posttransplant resource utilization (hospital length of stay and hospital charges). Age, sex, race, etiology of disease, and cold ischemia time were similar among the three groups. Patient survival, patient/graft survival, and hospital charges were not statistically different between the three groups. The median length of stay was statistically different only between groups B and C (P =.006). Our data support the idea that if severely ill patients with end-stage liver disease are selected appropriately, liver transplant outcomes are similar to those observed among subjects who are less ill and are transplanted electively from home.

Female↗

PubMed2002

Crystalline order on a sphere and the generalized Thomson problem.

We attack the generalized Thomson problem, i.e., determining the ground state energy and configuration of many particles interacting via an arbitrary repulsive pairwise potential on a sphere via a continuum mapping onto a universal long range interaction between angular disclination defects parametrized by the elastic (Young) modulus Y of the underlying lattice and the core energy E(core) of an isolated disclination. Predictions from the continuum theory for the ground state energy agree with numerical simulations of long range power law interactions of the form 1/r(gamma) (0<gamma<2) to four significant figures. The generality of our approach is illustrated by a study of grain boundary proliferation for tilted crystalline order and square lattices on the sphere.

Journal Article↗

PubMed2002

Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial.

BACKGROUND: The objective of this prospective controlled trial was to investigate the ability of a group of serum and peritoneal fluid (PF) markers to predict, non-surgically, endometriosis. METHODS AND RESULTS: Serum and PF samples were obtained from 130 women while undergoing laparoscopy for pain, infertility, tubal ligation or sterilization reversal. Concentrations of six cytokines [interleukin (IL)-1beta, IL-6, IL-8, IL-12, IL-13 and tumour necrosis factor (TNF)-alpha] were measured in serum and PF, and reactive oxygen species (ROS) in PF, and levels were compared among women who were allocated to groups according to their post-surgical diagnosis. Fifty-six patients were diagnosed with endometriosis, eight with idiopathic infertility, 27 underwent tubal ligation or reanastomosis (control group) and 39 were excluded due to bloody PF. Only serum IL-6 and PF TNF-alpha could be used to discriminate between patients with and without endometriosis with a high degree of sensitivity and specificity (P < 0.001). A threshold of 15 pg/ml PF TNF-alpha provided 100% sensitivity and 89% specificity (positive likelihood ratio of 9.1 and negative likelihood ratio of 0). A threshold of 2 pg/ml for serum IL-6 provided a sensitivity of 90% and specificity of 67% (positive likelihood ratio of 2.7 and negative likelihood ratio of 0.14). CONCLUSIONS: By measuring serum IL-6 and PF TNF-alpha, it was possible to discriminate between patients with endometriosis and those without. Before these markers can be used as a non-surgical diagnostic tool, these data should be verified in a larger study.

Adult↗

PubMed2002

Liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the commonest malignancies worldwide, and accounts for more than 1 million deaths annually. Identification of tumors early in the course of disease appears to be important for treatment, yet remains difficult to accomplish. Without treatment the prognosis is dismal with a median survival of 6-9 months. Partial hepatic resection is generally accepted as the treatment of choice for HCC with reported survival rates of up to 50% at 5 years. Unfortunately poor underlying liver function as well as tumor number or location preclude traditional hepatic resection in many cases. Total hepatectomy with transplantation (LT) has been advocated such cases, but the results have been variable. LT offers the advantage of radical tumor removal even in patients with multifocal disease or severe cirrhosis. Additionally, LT removes the possibility of metachronous lesions developing in the liver remnant and restores normal liver function. The critical limitation to advocating LT as primary oncotherapy in patients with HCC is the severe shortage of donor livers. Until organ availability improves, transplantation for HCC can only be offered to patients whose survival is predicted to be similar to that in patients transplanted for benign disease. This report reviews the current role and indications for liver transplantation as therapy for hepatocellular carcinoma.

Asia↗

PubMed2001

Hexatic order and surface ripples in spherical geometries.

In flat geometries, two-dimensional hexatic order has only a minor effect on capillary waves on a liquid substrate and on undulation modes in lipid bilayers. However, extended bond-orientational order alters the long-wavelength spectrum of these ripples in spherical geometries. We calculate this frequency shift and suggest that it might be detectable in lipid bilayer vesicles, at the surface of liquid metals, and in multielectron bubbles in liquid helium at low temperatures. Hexatic order also leads to a shift in the threshold for the fission instability induced in the later two systems by an excess of electric charge.

Journal Article↗

PubMed2001

Shear response of a smectic film stabilized by an external field.

The response of a field-stabilized two-dimensional smectic liquid crystal to shear stress is discussed. Below a critical temperature the smectic film exhibits elastic response to an infinitesimal shear stress normal to the layering. At finite stresses free dislocations nucleate and relax the applied stress. The coupling of the dislocation current to the stress results in non-Newtonian viscous flow. The flow profile in a channel geometry is shown to change qualitatively from a power-law dependence to a Poiseuille-like profile upon increasing the pressure head.

Journal Article↗

PubMed2001

Chemical and physical analyses of wax ester properties.

Wax esters are major constituents of the surface lipids in many terrestrial arthropods, but their study is complicated by their diversity. We developed a procedure for quantifying isomers in mixtures of straight-chain saturated and unsaturated wax esters having the same molecular weights, using single-ion monitoring of the total ion current data from gas chromatography-mass spectrometry. We examined the biological consequences of structural differences by measuring the melting temperatures, T(m), of >60 synthetic wax esters, containing 26-48 carbon atoms. Compounds containing saturated alcohol and acid moieties melted at 38-73 degrees C. The main factor affecting T(m) was the total chain length of the wax ester, but the placement of the ester bond also affected T(m). Insertion of a double bond into either the alcohol or acid moiety decreased T(m) by approximately 30 degrees C. Simple mixtures of wax esters with n-alkanes melted several degrees C lower than predicted from the melting points of the component lipids. Our results indicate that the wax esters of primary alcohols that are most typically found on the cuticle of terrestrial arthropods occur in a solid state under physiological conditions, thereby conferring greater waterproofing. Wax esters of secondary alcohols, which occur on melanopline grasshoppers, melted >60 degrees C below primary esters of the same molecular weight and reduced T(m) of the total surface lipids to environmental values.

Animals↗

PubMed2001

Novel phases and reentrant melting of two-dimensional colloidal crystals.

We investigate two-dimensional (2D) melting in the presence of a one-dimensional (1D) periodic potential as, for example, realized in recent experiments on 2D colloids subjected to two interfering laser beams. The topology of the phase diagram is found to depend primarily on two factors: the relative orientation of the 2D crystal and the periodic potential troughs, which selects a set of Bragg planes running parallel to the troughs, and the commensurability ratio p=a(')/d of the spacing a(') between these Bragg planes to the period d of the periodic potential. The complexity of the phase diagram increases with the magnitude of the commensurabilty ratio p. Rich phase diagrams, with "modulated liquid," "floating," and "locked floating" solid and smectic phases are found. Phase transitions between these phases fall into two broad universality classes, roughening and melting, driven by the proliferation of discommensuration walls and dislocations, respectively. We discuss correlation functions and the static structure factor in these phases, and make detailed predictions about the universal features close to the phase boundaries. We predict that for charged systems with highly screened short-range interactions, these melting transitions are generically reentrant as a function of the strength of the periodic potential, a prediction that is in accord with recent 2D colloid experiments. Implications of our results for future experiments are also discussed.

Journal Article↗

PubMed2001

Vascular antithrombin and clinical outcome in heart transplant patients.

A procoagulant microvasculature is associated with accelerated development of coronary artery disease (CAD) and failure in heart transplant patients. This study was performed to evaluate how changes in natural anticoagulation within cardiac allografts affect outcome. We prospectively studied 141 consecutive cardiac allograft recipients who underwent transplantation between 1988 and 1997. Serial endomyocardial biopsy specimens (6.5 +/- 0.1 biopsy specimens/patient) obtained during the first 3 months after transplantation were studied immunohistochemically to evaluate vascular antithrombin, and annual coronary angiograms (3.8 +/- 0.2 angiograms/patient) were studied to evaluate CAD. Antithrombin was present in arteries and veins, but not in capillaries, of all donor heart biopsy samples. Allografts that maintained vascular antithrombin had the best prognosis. Allografts with early and persistent loss of vascular antithrombin (n = 21) developed CAD earlier (p < 0.001), developed more severe disease (p < 0.001), showed more disease progression (p < 0.001), and failed more often (p = 0.003) and earlier (p < 0.001) than allografts retaining normal vascular antithrombin (n = 45). However, allografts that lost and recovered vascular antithrombin while developing unusual capillary antithrombin binding (n = 75) had less CAD, developed CAD later, had less severe disease and less disease progression (p < 0.01), and failed less often (p = 0.01) and later (p = 0.03) than allografts with persistent loss of vascular antithrombin. The persistent lack of a thromboresistant microvasculature increases risk of subsequent CAD and graft failure. However, recovery of vascular antithrombin and development of unusual capillary antithrombin binding improves allograft outcome.

Antithrombins↗

PubMed2001

DNA damage in patients with untreated cancer as measured by the sperm chromatin structure assay.

OBJECTIVE: To examine the relationship between sperm chromatin defects, evaluated by sperm chromatin structure assay (SCSA) and semen characteristics in cryopreserved semen specimens from patients diagnosed with various types of cancer. DESIGN: Prospective study. SETTING: Andrology laboratory at a tertiary care hospital. PATIENT(S): Cryopreserved semen samples from 12 healthy fertile men and 37 men diagnosed with cancer: testicular cancer (n = 20), Hodgkin's disease (n = 11), non-Hodgkin's disease (n = 4), and other neoplasm (n = 2). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The shift of green (native DNA) to red (denatured, single-stranded DNA) fluorescence in acridine orange-stained nuclei was measured and quantified using the expression alpha(t)(red fluorescence/[red + green fluorescence] per cell). Sperm DNA damage was correlated with classical semen characteristics. RESULT(S): Cancer patients as a group had significantly higher DNA damage when compared with controls. Specimens with high COMPalpha(t) values (percentage of sperm with denatured DNA) were present in all groups of cancer patients. No meaningful correlation was seen between the extent of DNA damage and classical semen measures. CONCLUSION(S): DNA damage in spermatozoa is prevalent in the majority of cancer patients. SCSA provides important information about the biochemical integrity of sperm DNA in men with cancer before their treatment.

Acridine Orange↗

PubMed2001

The immunopathogenesis of hepatitis C virus infection.

The outcome of HCV infection is determined by the interaction between the virus and the host immune system. The persistence of infection in most HCV-infected individuals, despite the presence of HCV-directed antibodies, suggests that such antibodies fail to induce viral clearance. Patients with self-limited hepatitis C have evidence of a polyclonal, multispecific CD8+ T-cell response along with a coordinated CD4+ T-cell response that is associated with eradication of HCV infection. Cytokines are produced both locally within the liver and systemically and may play an important role in controlling viral replication and contributing to hepatocellular damage through amplification of a nonspecific immune response. In most patients, the humoral, cellular immune, and cytokine response seem insufficient to eradicate infection. In its attempt to clear the virus from the liver, the immune system contributes to the hepatocellular injury seem in most chronically infected patients. A better understanding of the host's immune response may provide further insight on the pathogenetic mechanisms involved in development of chronic hepatitis and aid the development of better therapeutic strategies.

Acute Disease↗

PubMed2001

Discovery of novel trimethylalkanes in the internal hydrocarbons of developing pupae of Heliothis virescens and Helicoverpa zea.

Novel trimethyl-branched alkanes which eluted with the monomethylalkanes were identified in the internal lipids of Helicoverpa zea but were not present in Heliothis virescens. Their structures were unique in that the first methyl branch occurred on carbon 2 and the 2nd and 3rd methyl branch points were separated by a single methylene. Novel trimethylalkanes identified from their chemical ionization and electron impact mass spectra were 2,18,20-trimethyltetratriacontane, 2,18,20-trimethylhexatriacontane, and 2,24,26-trimethyldotetracontane. Previous reports did not find these trimethylalkanes in the cuticular surface lipids of larvae, pupae or adults of either species. The internal pupal hydrocarbons of H. virescens and H. zea amounted to 123 microg and 304 microg per pupa, respectively. They consisted of n-alkanes (8 and 4%, respectively) and methyl-branched alkanes (88 and 94%, respectively). The n-alkanes ranged in chain length from approximately 21 to 35 carbons and the methyl-branched alkanes from approximately 26 to 55 carbons vs. methyl-branched alkanes from 28 to 37 carbons previously reported for hydrocarbons from the pupal cuticular surface. The major n-alkane was heptacosane (3.3 and 1.2%, respectively, in H. virescens and H. zea). The major methyl-branched alkanes in H. virescens were methylhentriacontane (15%), methyltritriacontane (12%) and dimethyltritriacontane (10%), and in H. zea were methylnonacosane (17%), dimethylnonacosane (9%) and methylhentriacontane (20%). Except for the novel trimethylalkanes, the methylalkane branch points were predominantly on odd-numbered carbons as has been reported for these and other species.

Animals↗

PubMed2001

Novel wax esters and hydrocarbons in the cuticular surface lipids of the red harvester ant, Pogonomyrmex barbatus.

The cuticular surface lipids of the red harvester ant, Pogonomyrmex barbatus, were found to contain minor amounts of novel wax esters, in addition to the major components, hydrocarbons. The wax esters ranged in carbon number from C19 to C31 and consisted of esters of both odd- and even-numbered alcohols and acids. Each wax ester with a given carbon number eluted at several different retention times indicating possible methyl branching in either the fatty acid or alcohol moiety, or in both moieties. Each eluting peak of wax esters consisted of a mixture of wax esters of the same carbon number in which the fatty acid moiety ranged from C8 to C18, and the alcohol moiety ranged from C8 to C17. Some wax esters were largely found on the head indicating they may be of a glandular origin. The hydrocarbons consisted of: n-alkanes, C23 to C33; odd-numbered n-alkenes, C27 to C35; and the major components, methyl-branched alkanes, C26 to over C49. Notable components of the methyl-branched alkanes were 2-methyltriacontane, and the novel trimethylalkanes with a single methylene between the first and second branch points, 13,15,19-trimethylhentriacontane and 13,15,21-trimethyltritriacontane.

Animals↗