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Biomedical subjects

P Kearney

Publications and source records attributed to P Kearney.

At least 19 recordsLinked to original sources
PubMed2003

Bioinformatics meets proteomics--bridging the gap between mass spectrometry data analysis and cell biology.

Proteomics research programs typically comprise the identification of protein content of any given cell, their isoforms, splice variants, post-translational modifications, interacting partners and higher-order complexes under different conditions. These studies present significant analytical challenges owing to the high proteome complexity and the low abundance of the corresponding proteins, which often requires highly sensitive and resolving techniques. Mass spectrometry plays an important role in proteomics and has become an indispensable tool for molecular and cellular biology. However, the analysis of mass spectrometry data can be a daunting task in view of the complexity of the information to decipher, the accuracy and dynamic range of quantitative analysis, the availability of appropriate bioinformatics software and the overwhelming size of data files. The past ten years have witnessed significant technological advances in mass spectrometry-based proteomics and synergy with bioinformatics is vital to fulfill the expectations of biological discovery programs. We present here the technological capabilities of mass spectrometry and bioinformatics for mining the cellular proteome in the context of discovery programs aimed at trace-level protein identification and expression from microgram amounts of protein extracts from human tissues.

Computational Biology↗
PubMed2002

Rapid clonal development in a relapsed CML 11 years post replete allogeneic bone marrow transplantation.

Long-term survival of chronic myeloid leukaemia (CML) patients transplanted in chronic phase with a replete marrow have been described previously. The same success has not been achieved with patients in more advanced stages of the disease. We describe a CML patient who received an allogeneic bone marrow transplantation in accelerated phase. Cytogenetic and molecular analysis confirmed donor chimaerism, and the absence of the BCR-ABL mRNA. Almost 12 years post-transplant relapse was noted. Cytogenetic analyses showed a complex evolving karyotype. These findings are correlated with the longitudinal molecular analysis utilising real-time and VNTR PCR.

Adolescent↗
PubMed2001

Telemedicine: a solution to the followup of rural trauma patients?

BACKGROUND: Outpatient followup of rural trauma patients is problematic for physicians and patients. Our hypothesis was that telemedicine-based followup of trauma patients discharged to remote areas is feasible and is associated with high patient and physician satisfaction. STUDY DESIGN: We chose 11 counties in Kentucky surrounding a remote telemedicine site as our region of interest. Any adult trauma patient who was discharged from our Level I trauma center to this geographic region was eligible to have routine followup appointment(s) at the TeleTrauma Clinic. Patients were examined and interviewed with the assistance of a nurse, an electronic stethoscope, and a close-up imaging instrument. Radiographs performed at the telemedicine site were viewed. Patients and physicians completed a survey after the appointment. RESULTS: To date, we have conducted 22 telemedicine-based followup assessments of trauma patients. The average age and Injury Severity Score were 42 years and 18, respectively. Plain radiographs were reviewed in 13 cases. Our patient surveys indicated a high degree of satisfaction with the teleappointment. In 15 of 22 patients, no further clinical followup was arranged. The differences in travel distances and times for an appointment at the TeleTrauma Clinic versus an appointment at our Level I trauma center were significant. The average and median duration of the appointments was 14 minutes. All telemedicine encounters were done by two physicians, who recorded a high level of satisfaction. CONCLUSIONS: Our early experience with the outpatient followup of remote trauma victims by telemedicine is encouraging. Patient surveys indicate a high degree of satisfaction. As a result of our favorable experience, telemedicine-based followup may be expanded to other regions of Kentucky.

Adolescent↗
PubMed2001

An information-based sequence distance and its application to whole mitochondrial genome phylogeny.

MOTIVATION: Traditional sequence distances require an alignment and therefore are not directly applicable to the problem of whole genome phylogeny where events such as rearrangements make full length alignments impossible. We present a sequence distance that works on unaligned sequences using the information theoretical concept of Kolmogorov complexity and a program to estimate this distance. RESULTS: We establish the mathematical foundations of our distance and illustrate its use by constructing a phylogeny of the Eutherian orders using complete unaligned mitochondrial genomes. This phylogeny is consistent with the commonly accepted one for the Eutherians. A second, larger mammalian dataset is also analyzed, yielding a phylogeny generally consistent with the commonly accepted one for the mammals. AVAILABILITY: The program to estimate our sequence distance, is available at http://www.cs.cityu.edu.hk/~cssamk/gencomp/GenCompress1.htm. The distance matrices used to generate our phylogenies are available at http://www.math.uwaterloo.ca/~mli/distance.html.

Animals↗
PubMed2001

Analysis of codon usage patterns of bacterial genomes using the self-organizing map.

Codon usage varies both between organisms and between different genes in the same organism. This observation has been used as a basis for earlier work in identifying highly expressed and horizontally transferred genes in Escherichia coli. In this work, we applied Kohonen's self-organizing map to analysis of the codon usage pattern of the Escherichia coli, Aquifex aeolicus, Archaeoglobus fulgidus, Haemophilus influenzae RD:, Methanococcus jannaschii, Methanobacterium thermoautotrophicum, and Pyrococcus horikoshii genomes for evidence of highly expressed genes and horizontally transferred genes. All of the analyzed genomes had a clear category of horizontally transferred genes, and their apparent percentages ranged from 7.7% to 21.4%. The apparent percentage of highly expressed genes ranges from 0% to 11.8%. A clustering of average codon usage of main gene categories of the seven genomes showed an interesting mixing of gene classes in four thermophilic/hyperthermophilic organisms, A. aeolicus, A. fulgidus, M. thermoautotrophicum, and P. horikoshii, which suggests possible origins of their horizontally transferred genes as well as the need for adaptation to a specific environment. Further classification of the three gene categories in E. coli and H. influenzae according to gene function revealed that genes involved in communication (such as regulation and cell process) and structure (cell structure and structural proteins) are more likely to be horizontally transferred than are genes involved in information (transcription, translation, and related processes) and in some groups of energy (such as energy metabolism and carbon compound catabolism).

Archaeoglobus fulgidus↗
PubMed2000

InVEST: interactive and visual edge selection tool for constructing evolutionary trees.

InVEST is an interactive and visual tool for constructing evolutionary trees from an ordered list of edges. In this paper it is shown that many methods for constructing evolutionary trees reduce to the edge selection problem. Furthermore, through a simulation study, it is shown that noninteractive methods for edge selection often perform poorly and can conceal alternative solutions. InVEST allows the user to interact with and explore an ordered list of edges facilitating the incorporation of user domain knowledge into the evolutionary tree construction process.

Algorithms↗
PubMed2000

Embodiment of evolutionary computation in general agents.

Holland's Adaptation in Natural and Artificial Systems largely dealt with how systems, comprised of many self-interested entities, can and should adapt as a whole. This seminal book led to the last 25 years of work in genetic algorithms (GAs) and related forms of evolutionary computation (EC). In recent years, the expansion of the Internet, other telecommunications technologies, and other large scale networks have led to a world where large numbers of semi-autonomous software entities (i.e., agents) will be interacting in an open, universal system. This development cast the importance of Holland's legacy in a new light. This paper argues that Holland's fundamental arguments, and the years of developments that have followed, have a direct impact on systems of general network agents, regardless of whether they explicitly exploit EC. However, it also argues that the techniques and theories of EC cannot be directly transferred to the world of general agents (rather than EC-specific) without examination of effects that are embodied in general software agents. This paper introduces a framework for EC interchanges between general-purpose software agents. Preliminary results are shown that illustrate the EC effects of asynchronous actions of agents within this framework. Building on this framework, coevolutionary agents that interact in a simulated producer/consumer economy are introduced. Using these preliminary results as illustrations, areas for future investigation of embodied EC software agents are discussed.

Algorithms↗
PubMed2000

Adrenaline, insulin and glucagon do not have acute effects on plasma leptin levels in sheep: development and characterisation of an ovine leptin ELISA.

Leptin, a recently discovered hormone secreted mainly from adipose tissue, was first described as a regulator of adiposity, food intake and energy metabolism. It is now apparent that leptin physiology is much more complex and is likely to play an important role in many other systems including reproduction, haematopoiesis and immunity. Leptin levels have been shown to be well correlated with body fat in both humans and rodents, with administration of exogenous leptin to rats and mice resulting in loss of body fat. Leptin is, therefore, likely to be an important humoral signal to the central nervous system on body composition and regulation of food consumption. Due to the limited cross-reactivity of leptin from other species in the current assays for leptin, physiological research on leptin has, to a large extent, been restricted to rodents and humans. The aim of this study was to develop a leptin immunoassay suitable for use with sheep, enabling the investigation of the basic physiology of leptin in an animal larger than rats or mice, thus allowing repeated blood sampling. Using this assay we investigated the short-term effects of insulin, adrenaline and glucagon (all modulators of blood glucose) on plasma leptin levels. Antiserum to bovine recombinant leptin (brLeptin) raised in chickens was used to develop a competitive ELISA. Using brLeptin as standard, the assay has a sensitivity of 0. 5 ng/ml with inter- and intra-assay variation of 15% and 7% respectively. The cross-reactivity of human recombinant leptin was 36.5%, while mouse leptin showed no cross-reactivity. Plasma samples from ewes, male castrate animals and rams (n=4-5) diluted in parallel to the standard with mean leptin concentrations of 6.0+/-2. 9, 3.3+/-0.4 and 3.1+/-1.3 ng/ml respectively. Leptin levels in rams were significantly lower than in ewes. The non-significant difference in leptin levels between rams and male castrate animals suggests that testosterone may not be responsible for the lower levels of leptin. Four groups of 3-4 ewes were given intravenous insulin (1 iu/kg), adrenaline (65 microg/kg), glucagon (24 iu/kg) or saline. Blood samples were taken at 1, 3, 5, 10, 20, 30, 60, 90 and 120 min after injection. As expected, glucose levels declined within 10 min of the insulin injection and rose after 3 min following both adrenaline and glucagon injections. Leptin levels, however, remained relatively unchanged for the 2 h following the treatments. Finally, a bolus intravenous dose of glucose (240 mg/kg) was given and sequential blood samples taken. Despite plasma glucose levels rising to over 200 mg/dl, leptin levels did not significantly change over the three hours following treatment. These data indicate that plasma leptin levels in sheep, in contrast to rodents, are not responsive to short-term changes in blood glucose or insulin, as has been shown in humans.

Animals↗
PubMed1999

Comparison of normal and diseased pulmonary artery morphology by intravascular ultrasound and histological examination.

The study was performed to determine the morphological characteristics of normal and diseased pulmonary arteries by ultrasound (intravascular ultrasound, IVUS) and histology. Forty-nine cadaver segments of pulmonary arteries from 16 postmortem patients were imaged in vitro by IVUS and compared to matched histological sections. The pulmonary vasculature of 11 patients with pulmonary hypertension was investigated in vivo by IVUS. In the in vitro study, 34 of a total of 143 histological sections of the segmental pulmonary arteries showed fibrotic wall components; the remaining 109 sections had regular components. Imaged by IVUS, the wall of the regular and fibrotic arteries revealed a single layer histologically, representing the intima, media, adventitia and connective tissue. Adjacent lung tissue could be detected by IVUS and was confirmed by the histological section. In three patients with a history of chronic embolic pulmonary hypertension, IVUS revealed thrombi or a double vessel wall layer. Histologically, the material extracted after pulmonary thromboendarterectomy in two patients showed wall-adherent thrombus features of early organization. In all other patients only a single wall layer was seen. The vessel walls (intima, media, adventitia and connective tissue) of regular and slightly fibrosed pulmonary arteries show only a single layer. Wall-adherent organized thrombi in chronic embolic pulmonary hypertension can be detected by IVUS as a second inner vessel layer. Thus IVUS may represent an additional tool for detecting chronic embolic pulmonary hypertension when the results of pulmonary angiography or computed tomography are not definite.

Adult↗
PubMed1998

Long-term outcome of autoimmune disease following allogeneic bone marrow transplantation.

OBJECTIVE: To investigate the long-term outcome of autoimmune disease following allogeneic bone marrow transplantation (BMT), and its relationship to hemopoietic chimerism. METHODS: Three previously described patients with rheumatoid arthritis (RA) who underwent allogeneic BMT for therapy-related severe aplastic anemia and 1 new patient with psoriasis who received BMT for chronic myeloid leukemia (CML) were followed up. Molecular studies were performed to assess hemopoietic and immune reconstitution in 3 cases. RESULTS: In 2 of the RA patients, the RA remained in remission without treatment, with nonprogressive disease, 11 and 13 years after BMT. The third patient with RA had a relapse 2 years after BMT, although the previously aggressive disease subsequently ran an attenuated course with treatment-free remission for the last 11 years. Comparison with other cases of RA suggests that graft-versus-host disease may influence the long-term outcome, perhaps through ongoing inhibition of the immune system. In the patient with psoriasis, BMT was followed by remission, but the psoriatic rash recurred and arthropathy developed 12 months later. The psoriasis and arthropathy remained active 4.5 years post-BMT, although the CML remained in remission. Molecular studies in the 2 patients whose RA remained in continued remission and in the patient with psoriasis that relapsed confirmed complete donor hemopoietic reconstitution. CONCLUSION: Long-term followup of autoimmune disease after allogeneic transplantation confirmed cure of the autoimmune disease in some, but eventual relapse in others. The occurrence of relapse despite complete donor hemopoietic reconstitution is evidence for the development of de novo, as opposed to persistent, disease, and is possibly related to intrinsic susceptibility of the transplanted stem cells or to host factors. There may be a relationship between remission of autoimmune disease and graft-versus-host reaction. These findings have relevance for the evolving application of stem cell transplantation as a therapy for autoimmune diseases.

Adult↗
PubMed1998

Rapid colorimetric assay for the detection of the bcr-abl rearrangement.

The value of the polymerase chain reaction (PCR) in the diagnosis of malignant disorders is well established. However, several factors such as sample type, storage conditions and extraction methodology affect the ability of the PCR to provide a diagnosis. We describe the use of a PCR-product-specific 'capture' oligo to overcome these potential problems. The detection of the captured product by standard ELISA technologies allowed a rapid colorimetric analysis to be performed removing the need for both gel electrophoresis and the performance of a nested PCR in order to reach a diagnosis. In a survey of 14 clinical samples this method was observed to be both more sensitive and specific than the PCR followed by gel electrophoresis.

Bone Marrow↗
PubMed1998

Ex vivo effects associated with the expression of a bcr-abl-specific ribozyme in a CML cell line.

The bcr-abl chimeric gene is found in 95% of chronic myeloid leukemia (CML) patients and is thought to be seminal to the etiology of the disease. The possibility of using ribozymes to suppress bcr-abl gene expression and subsequently alter the malignant phenotype of hematopoietic cells may provide an alternative therapeutic approach to current regimens. A series of hammerhead ribozymes targeted to a b3a2 bcr-abl transcript has been developed and previously shown to be capable of cleaving the desired sequence with varying degrees of specificity. This study investigated the ex vivo effects of endogenous expression of these ribozymes in a CML cell line, K562. We demonstrated a 53% decrease in bcr-abl mRNA levels in a clone induced to express Rz8, compared with its uninduced control. Phenotypic analysis of this clone also revealed a 63% decrease in colony-forming ability and a 43% inhibition of cell proliferation following ribozyme expression. Morphologic analysis of cells showed there was a slight increase (2.5% to 15%) in the number of cells undergoing apoptosis. These results suggest that Rz8 was effective in suppressing bcr-abl gene expression within a cellular environment and altering the leukemic nature of a CML cell line.

Fusion Proteins, bcr-abl↗