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Biomedical subjects

E Harley

Publications and source records attributed to E Harley.

15 recordsLinked to original sources
PubMed2001

Uniform integration of genome mapping data using intersection graphs.

MOTIVATION: The methods for analyzing overlap data are distinct from those for analyzing probe data, making integration of the two forms awkward. Conversion of overlap data to probe-like data elements would facilitate comparison and uniform integration of overlap data and probe data using software developed for analysis of STS data. RESULTS: We show that overlap data can be effectively converted to probe-like data elements by extracting maximal sets of mutually overlapping clones. We call these sets virtual probes, since each set determines a site in the genome corresponding to the region which is common among the clones of the set. Finding the virtual probes is equivalent to finding the maximal cliques of a graph. We modify a known maximal-clique algorithm such that it finds all virtual probes in a large dataset within minutes. We illustrate the algorithm by converting fingerprint and Alu-PCR overlap data to virtual probes. The virtual probes are then analyzed using double-linkage intersection graphs and structure graphs to show that methods designed for STS data are also applicable to overlap data represented as virtual probes. Next we show that virtual probes can produce a uniform integration of different kinds of mapping data, in particular STS probe data and fingerprint and Alu-PCR overlap data. The integrated virtual probes produce longer double-linkage contigs than STS probes alone, and in conjunction with structure graphs they facilitate the identification and elimination of anomalies. Thus, the virtual-probe technique provides: (i) a new way to examine overlap data; (ii) a basis on which to compare overlap data and probe data using the same systems and standards; and (iii) a unique and useful way to uniformly integrate overlap data with probe data.

Algorithms↗
PubMed1999

Phylogenetic relationships in the bovid subfamily Antilopinae based on mitochondrial DNA sequences.

A molecular phylogeny of the subfamily Antilopinae was determined using the two mitochondrial DNA (mtDNA) genes cytochrome b and cytochrome c oxidase III. The tribe Antilopini is monophyletic with Antidorcas marsupialis and Litocranius walleri basal to the large genus Gazella. Antilope cervicapra falls within Gazella. This placement would either make Gazella paraphyletic or require that the genus name Gazella be changed to Antilope. Gazella thomsonii is supported as a subspecies of G. rufifrons. Most members of the tribe Neotragini are sister species to the Antilopini, but the Neotragini is rendered paraphyletic by a deep placement of Neotragus moschatus.

Animals↗
PubMed1999

Revealing hidden interval graph structure in STS-content data.

MOTIVATION: STS-content data for genomic mapping contain numerous errors and anomalies resulting in cross-links among distant regions of the genome. Identification of contigs within the data is an important and difficult problem. RESULTS: This paper introduces a graph algorithm which creates a simplified view of STS-content data. The shape of the resulting structure graph provides a quality check - coherent data produce a straight line, while anomalous data produce branches and loops. In the latter case, it is sometimes possible to disentangle the various paths into subsets of the data covering contiguous regions of the genome, i.e. contigs. These straight subgraphs can then be analyzed in standard ways to construct a physical map. A theoretical basis for the method is presented along with examples of its application to current STS data from human genome centers. AVAILABILITY: Freely available on request.

Algorithms↗
PubMed1996

Elevated cellular polyamine levels enhance promoter activity in vivo.

Polyamines are small polycationic molecules that have been implicated in cell growth, differentiation and transformation. A possible mechanism for their involvement in these processes is via their influence on the expression of growth promoting genes. In this study we used an ornithine decarboxylase (ODC) overexpressing retroviral system to achieve high intracellular levels of polyamines in epidermal cells. We then looked at the effect this environment had on transcription from several promoter-reported gene constructs, including c-myc and ODC itself. In transient transfection studies elevated polyamines significantly enhanced the transcriptional activity of all promoters tested. In addition, reporter gene expression was induced approximately 3 fold in stable transformants containing an integrated c-myc or ODC promoter-reporter gene construct suggesting that elevated levels of polyamines, such as those found in transformed cells, have a stimulatory effect on gene expression.

Animals↗
PubMed1996

Good maps are straight.

This paper proposes a simplified approach to the assembly of large physical genome maps. The approach focuses on two key problems: (i) the integration of diverse forms of data from numerous sources, and (ii) the detection and removal of errors and anomalies in the data. The approach simplifies map assembly by dividing it into three phases-overlap, linkage and ordering. In the first phase, all forms of overlap data are integrated into a simple abstract structure, called clusters, where each cluster is a set of mutually-overlapping DNA segments. This phase filters out many questionable overlaps in the mapping data. In the second phase, clusters are linked together into a weighted intersection graph. False links between widely separated regions of the genome show up as crooked, branching structures in the graph. Removing these false links produces graphs that are straight, reflecting the linear structure of chromosomes. From these straight graphs, the third phase constructs a physical map. Graph algorithms and graph visualization play key roles in implementing the approach. At present, the approach is at an early stage of development: it has been tested on real and simulated mapping data, and the results look promising. This paper describes the first two phases of the approach in detail, and reports on our progress to date.

Chromosomes, Human, Pair 7↗
PubMed1994

A flexible approach to genome map assembly.

A major goal of the Human Genome Project is to construct detailed physical maps of the human genome. A physical map is an assignment of DNA fragments to their locations on the genome. Complete maps of large genomes require the integration of many kinds of experimental data, each with its own forms of noise and experimental error. To facilitate this integration, we are developing a flexible approach to map assembly based on logic programming and data visualization. Logic programming provides a convenient and mathematically rigorous way of reasoning about data, while data visualization provides layout algorithms for assembling and displaying genome maps. To demonstrate the approach, this paper describes numerous rules for map assembly implemented in a data-visualization system called Hy+. Using these rules, we have successfully assembled contigs (partial maps) from real and simulated mapping data-data that is noisy, imprecise and contradictory. The main advantage of the approach is that it allows a user to rapidly develop, implement and test new rules for genome map assembly, with a minimum of programming effort.

Chromosome Mapping↗
PubMed1989

Vocal cord paralysis.

The information presented in this article demonstrates that unilateral or bilateral vocal cord paresis or paralysis in infants and children is difficult to diagnose and difficult to manage. In an attempt to provide the otolaryngologist with a concise set of relevant guidelines, the following rules for management are presented here. 1. Suspect bilateral abductor vocal cord paralysis (BAVP) when a neonate or infant presents with high-pitched inspiratory stridor and evidence of airway compromise. Factors that should increase the suspicion of BAVP include associated Arnold-Chiari malformation; congenital anatomic abnormality involving the mediastinum (for example, tracheoesophageal fistula, vascular ring, other vascular anomalies); dysmorphic syndromes, especially those involving brainstem dysfunction; and manifest findings indicative of neuromuscular disorder. The neonate or infant with Arnold-Chiari malformation and inspiratory stridor has bilateral abductor vocal cord paralysis until proven otherwise. 2. Suspect unilateral vocal cord paresis or paralysis in an infant or child with hoarse voice, low-pitched cry, or breathy cry or voice. The infant who develops mild stridor and hoarse cry following surgical repair of a patent ductus arteriosus or tracheoesophageal fistula has a unilateral vocal cord paralysis until proven otherwise. 3. Direct laryngoscopy with the flexible fiberoptic nasopharyngolaryngoscope and photodocumentation using a videocassette recorder offers the best method for diagnosis of vocal cord paresis or paralysis. Additional diagnostic studies that may be helpful include radiographic studies, CT scan, MRI scan, electromyography of the larynx, and, in older children, stroboscopy. 4. In using a flexible direct laryngoscope be careful not to interpret all motions of the vocal cords or arytenoids as evidence to preclude the diagnosis of vocal cord paralysis or paresis and be careful not to mistake the anterior intraluminal portion of a normal cricoid for an "anterior glottic web." 5. Tracheotomy is often required in order to assure adequate airway during infancy for children with BAVP. However, with the advent of sophisticated cardiorespiratory monitoring equipment and methods for monitoring blood oxygen and carbon dioxide levels, tracheotomy can be delayed until attempts have been made to improve the adequacy of the airway with neurosurgical intervention or other procedures.(ABSTRACT TRUNCATED AT 400 WORDS)

Child↗
PubMed1987

A clinical evaluation of gold-plated tubes for middle-ear ventilation.

Gold-plated tympanostomy tubes have been recently marketed as possessing qualities making them ideal for middle-ear ventilation. The performance of these tubes was compared with that of similarly designed Teflon tubes in a controlled, prospective study. Twenty-eight children underwent bilateral myringotomy and tube placement. One ear was randomly chosen for intubation with a gold-plated tube, and a Teflon tube was inserted into the other ear. Patients were examined monthly for 12 months and evaluated for otorrhea, tube occlusion, and early tube extrusion. Although the incidence of otorrhea and tube occlusion were higher for the gold-plated tube, these differences were not statistically significant. The gold-plated tube had a significantly higher rate of early extrusion than the Teflon tube. Based on these findings, there appears to be no advantage to using gold-plated tubes for middle-ear ventilation.

Child↗
PubMed1986

Protoporphyrinogen oxidase and porphobilinogen deaminase in variegate porphyria.

Two enzymes of the haem biosynthetic pathway were investigated in patients with variegate porphyria. Protoporphyrinogen oxidase in cultures of Epstein-Barr virus transformed lymphoblasts from twenty-seven patients showed a mean maximal velocity (Vmax) of 0.39 +/- 0.08+ nmol of protoporphyrin mg protein-1 h-1, a 52% reduction (P less than 0.001) from a non-porphyric control group (0.82 +/- 0.10). Km values (1.00 +/- 0.27 microM) did not differ significantly (P greater than 0.05) from control values in any of the patients. The mean Vmax of porphobilinogen deaminase in the cultures was 1.50 +/- 0.18 nmol of uroporphyrin mg protein-1 min-1, a 24% reduction (P less than 0.001) from controls (1.94 +/- 0.14). Mean porphobilinogen deaminase activity in the erythrocytes of twenty-one patients with variegate porphyria was 8.37 +/- 1.99 nmol of uroporphyrin 1 erythrocytes-1 s-1, a 28% reduction (P less than 0.001) from normal (11.98 +/- 2.11). The reduced activities of these two enzymes comply with the expression of variegate porphyria during its quiescent and acute phases.

Ammonia-Lyases↗
PubMed1980

Infectious drug resistance during an outbreak of samonellosis.

The sudden acquisition of aminoglycoside resistance among Salmonella group C1 isolates causing summer diarrhoea raised the possibility oif plasmid-mediated reistance. The demonstration of circular DNA species in the resistant, but not in the sensitive salmonellae and the transfer by conjugation of antibiotic resistance to a sensitive strain of Escherichic coli, was consistent with plasmid-mediated resistance.

Anti-Bacterial Agents↗
PubMed1977

Quantitative studies on the precursors of cytotoxic lymphocytes. I. Characterization of a clonal assay and determination of the size of clones derived from single precursors.

A microculture system for estimating the frequency of cytotoxic lymphocyte precursors (CLP) to alloantigens is described. Cytotoxic T lymphocytes (CL) were generated by culturing limiting numbers of RNC (H-2k)-nu/+lymph node (LN) cells with irradiated C3D2F1 (H-2k/d) spleen cells in the presence of RNC-nu/nu spleen cells for 7 days in microtiter trays. At the end of the culture period, individual wells were assayed for cytotoxic effector cells directed against 51CrP815 (H-2d) target cells. The effector cells generated under these conditions are sensitive to killing by rabbit anti-mouse brain serum and guinea pig complement. The process of differentiation from precursors to CL is radiation sensitive (Do approximately 180 rads). The frequency of precursors for H-2d was calculated by fitting the proportion of nonresponding cultures to the zero order term of the Poisson distribution, Po = e-vn, where Po = per cent nonresponders, v = precursor frequency, and N = number of LN cells cultured per well. The frequency of precursors in the RNC-nu/+LN population responding to the H-2d haplotype was found to be 1 in 776. Under conditions where no backstimulation is possible, the frequency of precursors responding to the H-2d haplotype is 1 in 885 for B6-nu/+LN and 1 in 2550 for B6-nu/+ spleen, respectively. In combination with a visual assay for individual CL, it was found that the average clone size per precursor after 7 days in culture is about 1040. Our assay could detect clones with as few as 40 CL/well. Since the average clone size in 26 times the detection limit, we conclude that the assay for CLP is highly sensitive and does not represent a minimum estimate.

Animals↗