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J Arnold

Publications and source records attributed to J Arnold.

At least 91 records · Page 5Linked to original sources
PubMed1996

A statistical test of a neutral model using the dynamics of cytonuclear disequilibria.

In this paper we use cytonuclear disequilibria to test the neutrality of mtDNA markers. The data considered here involve sample frequencies of cytonuclear genotypes subject to both statistical sampling variation as well as genetic sampling variation. First, we obtain the dynamics of the sample cytonuclear disequilibria assuming random drift alone as the source of genetic sampling variation. Next, we develop a test statistic using cytonuclear disequilibria via the theory of generalized least squares to test the random drift model. The null distribution of the test statistic is shown to be approximately chi-squared using an asymptotic argument as well as computer simulation. Power of the test statistic is investigated under an alternative model with drift and selection. The method is illustrated using data from cage experiments utilizing different cytonuclear genotypes of Drosophila melanogaster. A program for implementing the neutrality test is available upon request.

Animals↗
PubMed1996

Recognizing the forest for the trees: testing temporal patterns of cladogenesis using a null model of stochastic diversification.

Computer simulations are developed and employed to examine the expected temporal distributions of nodes under a null model of stochastic lineage bifurcation and extinction. These Markovian models of phylogenetic process were constructed so as to permit direct comparisons against empirical phylogenetic trees generated from molecular or other information available solely from extant species. For replicate simulated phylads with n extant species, cumulative distribution functions (cdf's) of branching times were calculated, and compared (using the Kolmogorov-Smirnov test statistic D) to those from three published empirical trees. Molecular phylogenies for columbine plants and avian cranes showed statistically significant departures from the null expectations, in directions indicating recent and ancient species' radiations, respectively, whereas a molecular phylogeny for the Drosophila virilis species group showed no apparent historical clustering of branching events. Effects of outgroup choice and phylogenetic frame of reference were investigated for the columbines and found to have a predictable influence on the types of conclusions to be drawn from such analyses. To enable other investigators to statistically test for nonrandomness in temporal cladogenetic pattern in empirical trees generated from data on extant species, we present tables of mean cdf's and associated probabilities under the null model for expected branching times in phylads of varying size. The approaches developed in this report complement and extend those of other recent methods for employing null models to assess the statistical significance of pattern in evolutionary trees.

Animals↗
PubMed1996

Rethinking grief: nursing implications for health promotion.

The healthy process of grieving is explored in relation to the nursing process. Grieving is postulated as facilitating growth and promoting health when viewed as a healing process. How one grieves determines to a large extent one's health and how one lives.

Adult↗
PubMed1996

Massively parallel algorithms for chromosome reconstruction.

Ordering clones from a genomic library into physical maps of whole chromosomes presents a central computational problem in genetics. Chromosome reconstruction via clone ordering is shown to be isomorphic to the NP-complete Optimal Linear Ordering problem. Massively parallel algorithms for simulated annealing based on Markov chain distribution are proposed and applied to this problem. Perturbation methods and problem-specific annealing heuristics are proposed and described. Experimental results on a 2048 processor MasPar MP-2 system are presented. Convergence, speedup and scalability characteristics of the various algorithms are analyzed and discussed.

Algorithms↗
PubMed1995

Manipulation of substrate utilization with somatostatin in patients with secondary multiple organ dysfunction syndrome.

OBJECTIVES: To determine whether glucose utilization and metabolic substrate (glucose and fat) oxidation could be manipulated in patients with secondary multiple organ dysfunction syndrome. DESIGN: Prospective study. SETTING: Intensive care units (ICU) of two university hospitals. PATIENTS: Eight adults free of hepatic disease and hemodynamically stable at the time of study, but with failed respiratory and gastrointestinal systems, who thus required mechanical ventilation and intravenous nutrition. INTERVENTIONS: Patients were infused with 20% dextrose through central venous cannulas at rates that increased and maintained (clamped) their plasma glucose concentration at 216 mg/dL (12 mmol/L) for 3 hrs. Somatostatin was infused continuously during the second and third hours of the clamp to reduce plasma concentrations of endogenous insulin and glucagon. Exogenous insulin was administered together with somatostatin during the third hour to restore basal insulin concentrations. Energy expenditure was measured by indirect calorimetry throughout the study and blood samples were withdrawn regularly for determination of metabolite and hormone concentrations. Main statistical comparisons were made between the baseline data (first hour of the study) and data collected during the second and third hours of the clamp. MEASUREMENTS AND MAIN RESULTS: Plasma glucagon concentrations were reduced by nearly 50% (p < .05) toward the end of the study, whereas no significant changes in plasma concentrations of cortisol or growth hormone occurred. Energy expenditure did not change significantly at any time during the clamp procedure. Glucose utilization (6.1 mg/kg/min [34 mumol/kg/min]) during the first hour of the hyperglycemic clamp, decreased by 53% (p < .05) with the infusion of somatostatin during the second hour of the clamp. However, once exogenous insulin was infused during the third hour, glucose utilization increased by 55% (p < .05) when compared with the baseline (hour 1) rate. Glucose oxidation was nearly doubled during the third hour of the study when compared with oxidation rates during the first and second hours. Fat oxidation decreased steadily during the 3-hr clamp. CONCLUSIONS: Glucagon has a significant inhibitory effect on glucose utilization during intravenous glucose infusion in the multiple organ dysfunction syndrome patient. Pharmacologic intervention with somatostatin and insulin (physiologic dose) can facilitate glucose utilization and oxidation in these patients. Further investigations are needed to determine whether long-term alteration of glucose and fat metabolism would be beneficial in the patient with secondary multiple organ dysfunction syndrome.

Aged↗
PubMed1995

Ocular manifestations of congenital rubella.

Ocular disease is a major component of the congenital rubella syndrome (CRS). Interest in this condition has been renewed after identification of a spectrum of delayed manifestations and the realization that sporadic cases of CRS will continue to occur despite vaccination programs due to reinfection in the immune patient. Work is continuing on strategies and planning of vaccination programs for disease prevention and control, refinements of diagnosis with particular emphasis on the prenatal diagnosis of fetal infection, and fundamental research into the pathogenic and immunologic mechanisms underlying CRS and its late manifestations.

Eye Diseases↗
PubMed1994

A fast random cost algorithm for physical mapping.

Ordering clones from a genomic library into physical maps of whole chromosomes presents a central computational/statistical problem in genetics. Here we present a physical mapping algorithm for creating ordered genomic libraries or contig maps by using a random cost approach [Berg, A. (1993) Nature (London) 361, 708-710]. This random cost algorithm is 5-10 times faster than existing physical mapping algorithms and has optimization performance comparable to existing procedures. The speedup in the algorithm makes practical the widespread use of bootstrap resampling to assess the statistical reliability of links in the physical map as well as the use of more elaborate physical mapping criteria to improve map quality. The random cost algorithm is illustrated by its application in assembling a physical map of chromosome IV from the filamentous fungus Aspergillus nidulans.

Aspergillus nidulans↗
PubMed1994

Tonometry to assess the adequacy of splanchnic oxygenation in the critically ill patient.

Tonometry, a relatively non-invasive technique for indirectly measuring the intramucosal pH (pHi) of the gastrointestinal tract, has recently been developed for use in critically ill patients. Reports in the literature suggest that the technique is of greatest benefit to patients at risk of developing reductions in splanchnic oxygenation (decreased O2 delivery) in whom early detection of the ischemic episode could possibly guide treatment. Tonometry, although still at a relatively early stage in its clinical development, could be of value for selected patient groups although further evaluation of the technique is necessary.

Clinical Trials as Topic↗
PubMed1994

CGP 47969A: a novel inhibitor of the synthesis of inflammatory cytokines.

CGP 47969A is a novel piperazine derivative that inhibits the synthesis of inflammatory cytokines, such as interleukin-1 alpha (IL-1), IL-1 beta and tumor necrosis factor alpha (TNF), in human monocytes stimulated with lipopolysaccharide (LPS), zymosan or IL-1 itself. IC50 values are in the range of 0.3-5 mumol/l. CGP 47969A does not inhibit total protein or RNA synthesis indicating selectivity for cytokine inhibition. CGP 47969A exerts its inhibitory effect at a post-transcriptional level, most probably by reducing translational efficiency of IL-beta mRNA, as steady-state levels of IL-1 beta mRNA are not inhibited while the primary translation product, the 31 kD IL-1 beta precursor molecule, is dose-dependently inhibited by CGP 47969A. The compound is devoid of cyclooxygenase and phospholipase A2 inhibitory activity but efficiently inhibits the generation of PGE2 and LTC4 in zymosan-stimulated mouse macrophages with an IC50 of 1.2 and 0.6 mumol/l, respectively. Antagonism of IL-1 and/or TNF is thought to have a beneficial effect on the course of inflammatory diseases. CGP 47969A may therefore represent a mechanistically new approach to the treatment of such diseases.

Animals↗
PubMed1994

Project WINS: integrating vocational services on mental health case management teams.

In an effort to expand employment opportunities available to psychiatric consumers, a research demonstration project was developed to incorporate vocational services into case management teams. Following psychiatric rehabilitation principles, Project WINS employs professionals as Vocational Specialists and consumers as Peer Support Specialists to work with clients and their case managers. This report describes the characteristics of clients eligible for WINS services, the implementation of the program, and the impact of WINS on clients and on the mental health and vocational systems. It also describes the challenges and barriers this innovative service is confronting.

Adult↗
PubMed1994

Size disparity in pediatric lung transplantation.

Donor scarcity and the limitations of organ preservation dictate that a wide size range be used to maximize effective donor utilization in pulmonary transplantation. Problems of size disparity are magnified in the pediatric population, where relevant dimensions vary considerably by age. There have been 10 pediatric lung recipients (7 bilateral, 2 single, 1 heart-lung) at our institution since 1991. The age range was 3 to 26 years (mean, 13.7), and the weight range was 15 to 57 kg (mean, 33.6). Diagnoses included cystic fibrosis (5), pulmonary fibrosis (2), pulmonary hypertension (2), and arteriovenous malformation (1). The donor-to-recipient weight ratio ranged from 0.45 to 1.9, and the donor-to-recipient thoracic height ratio ranged from 0.6 to 1.6. Lobar resection and delayed chest closure was required in one case and was successful. Cardiopulmonary bypass was used electively in seven cases. No reexplorations for bleeding were necessary. Two of the three hospital deaths resulted from right ventricular failure, judged to be secondary to excessive pulmonary artery pressures intraoperatively associated with small donor allografts. Elective bypass had not been used. Inhaled nitric oxide (6 patients) and/or extracorporeal membrane oxygenation (2 patients) were used for temporary postoperative support. The hospital survival rate was 70% (7/10). One late death occurred 14 months postoperatively and was caused by obliterative bronchiolitis. The authors conclude that size disparity is a significant problem in pediatric lung transplantation. However, with elective use of cardiopulmonary bypass and aggressive postoperative support, a broad size range can be used.

Adolescent↗
PubMed1994

Endosome-lysosomes and neurodegeneration.

A number of the major human and animal neurodegenerative diseases, such as Alzheimer's disease and sheep scrapie, are characterised by deposits of amyloid, arising through incomplete breakdown of membrane proteins. Although our knowledge concerning these diseases is increasing, they remain largely untreatable. Recently, attention has focussed on the mechanisms of production of different types of amyloid and the likely involvement within cells of acid compartments called endosome-lysosomes. These organelles may be 'bioreactor' sites for the unfolding and partial degradation of membrane proteins to generate the amyloid materials. These subsequently become expelled from the cell, or are released from dead cells, and accumulate as pathological entities. Common features of the disease processes give new direction to therapeutic intervention.

Alzheimer Disease↗
PubMed1994

Proliferating cell nuclear antigen expression in Wistar rat livers. A retrospective immunohistochemical study of normal and neoplastic livers.

Formalin-fixed, paraffin-embedded liver specimens from 27 2-year-old Wistar rats, including 10 normal livers, 11 hepatocellular adenomas, 2 hepatocellular carcinomas, and 4 cystic cholangiomas, were immunostained using the streptavidin/peroxidase method and the PC10 monoclonal antibody (Mab), which recognizes an epitope on the proliferating cell nuclear antigen (PCNA). The following PCNA labeling index (LI) mean values were found for the above four groups of liver specimens: normal livers, 0.43 +/- 0.31%; hepatocellular adenomas, 1.51 +/- 0.59%; hepatocellular carcinomas, 24.80% +/- 10.28%; and cystic cholangiomas, 0.61 +/- 0.21%. Our findings indicate that PCNA LI clearly separates liver malignancies from other benign liver tumors, as well as from normal, non-neoplastic, liver tissues. Although the mean PCNA LI values seemed to reflect histological grading (i. e. normal, neoplastic benign, neoplastic malignant), overlapping between normal livers and hepatocellular adenomas was observed in five cases (i. e. in 2 normal livers and 3 hepatocellular adenomas, where the PCNA LI values varied between 0.74% and 0.96%). It thus appears that PCNA immunohistochemistry represents a promising tool for investigating liver cell proliferation in laboratory rats, and permits distinguishing between benign and malignant liver parenchymal tumors.

Animals↗
PubMed1994

ODS_BOOTSTRAP: assessing the statistical reliability of physical maps by bootstrap resampling.

In the program ODS_BOOTSTRAP we provide a methodology for quickly ordering clones in a genomic library into a physical map and for applying a statistical tool known as the bootstrap to assess the statistical reliability of a clonal ordering. Each clone is assigned a binary fingerprint by one of a variety of experimental approaches to physical mapping. For example, the binary fingerprints might be generated by hybridizing a panel of m probes to a library of n clones. The resulting n x m binary data matrix, X, is input to ODS_BOOTSTRAP, which utilizes the similarity in binary fingerprints of clones to construct a physical map. Under this particular implementation of bootstrap resampling, the m probes (or columns of the data matrix) are sampled randomly with replacement in the computer to generate a new n x m data matrix, X*, from which a second physical map is constructed. The resampling process is repeated 100 or more times to generate 100 or more X* matrices. The resulting 100 or more physical maps are compared with the original physical map based on the original data matrix X by counting how often links in the original physical map reappear. Three confidence statistics are introduced for each link in a physical map. The statistic C1 is defined as the percentage of time two neighboring clones on the original map reappear as neighbors under resampling. The statistic C2 is defined as the percentage of time that two neighboring clones i and j on the original map reappear as neighbors or that a clone with an identical binary fingerprint to clone i reappears as a neighbor to clone j. The statistic C3 is defined as the percentage of time that two neighboring clones on the original map reappear in the same contig under resampling.

Algorithms↗
PubMed1994

Molecular evolution of a multigene family in group A streptococci.

The emm genes are members of a gene family in group A streptococci (GAS) that encode for antiphagocytic cell-surface proteins and/or immunoglobulin-binding proteins. Previously sequenced genes in this family have been named "emm," "fcrA," "enn," "arp," "protH," and "mrp"; herein they will be referred to as the "emm gene family." The genes in the emm family are located in a cluster occupying 3-6 kb between the genes mry and scpA on the chromosome of Streptococcus pyogenes. Most GAS strains contain one to three tandemly arranged copies of emm-family genes in the cluster, but the alleles within the cluster vary among different strains. Phylogenetic analysis of the conserved sequences at the 3' end of these genes differentiates all known members of this family into four evolutionarily distinct emm subfamilies. As a starting point to analyze how the different subfamilies are related evolutionarily, the structure of the emm chromosomal region was mapped in a number of diverse GAS strains by using subfamily-specific primers in the polymerase chain reaction. Nine distinct chromosomal patterns of the genes in the emm gene cluster were found. These nine chromosomal patterns support a model for the evolution of the emm gene family in which gene duplication followed by sequence divergence resulted in the generation of four major-gene subfamilies in this locus.

Amino Acid Sequence↗
PubMed1994

Intraoperative evaluation of big-endothelin plasma levels during liver transplantation in different vascular compartments.

Endothelin-1 (ET) is derived from its precursor big-ET, secreted by endothelial cells of multiple origin. The role of ET peptides in the physiological responses after orthotopic liver transplantation (OLT) was investigated. Venous big-ET plasma levels were analysed by RIA in 28 patients before and after OLT. Samples for analysis were taken intraoperatively from 12 patients from the caval, portal and hepatic veins and the radial artery at multiple time points. Highest caval levels were found during the anhepatic period and 60 min after reperfusion, followed by a drop and subsequent increase postoperatively. Highest levels in the hepatic and portal veins were detected during explanation and reperfusion. A different pattern was found in the radial artery. Values during rejection and infection were elevated compared with preoperative and postoperative levels. The heterogeneity of the kinetics points to different sites of ET generation, including liver and splanchnic circulation. It suggests a predominant paracrine secretion mode of ET peptides with various stimuli involved. Big-ET levels could reflect endothelial cell damage, as big-ET is generated intracellularly and biological activity is rather weak.

Adult↗