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Biomedical subjects

K Byrne

Publications and source records attributed to K Byrne.

At least 19 recordsLinked to original sources
PubMed1998

Education in informatics in medicine and the health sciences--the need for relevance.

At the University of Newcastle, the 5-year undergraduate programme in Medicine has been developed as a problem-based, self-directed, fully integrated curriculum. Curricular integration involves not only the basic and clinical sciences, but also population medicine, critical reasoning and the development of a broad range of professional skills. Medical informatics has been seen as an increasingly important professional skill and the integrated nature of the curriculum has provided an appropriate setting for the introduction and continuing development of this component of the curriculum. Over the last 3 years this component has been developed to be incorporated into the curriculum for the health sciences within the faculty, becoming health informatics. Informatics for undergraduate students in medicine and allied health professions must be developed as a relevant and useful component of the curriculum.

Allied Health Personnel↗
PubMed1998

NCAM: a polymorphic microsatellite locus conserved across eutherian mammal species.

A dinucleotide microsatellite was found to be conserved at the 3' untranslated end of the neural cell adhesion molecule (NCAM) gene in cattle, rat and human. The high level of sequence conservation found in this gene allows the use of a single set of PCR primers to amplify sequence spanning the repeat in many species. Sequence analysis revealed the conservation of the dinucleotide repeat in all eutherian mammal species studied with variation in length as well as internal structure caused by base substitutions. Polymorphisms were seen across five mammalian orders, in rat, buffalo, sheep, cow, whale and dolphin, with polymorphisms predicted in pig and dugong based on the length of the uninterrupted dinucleotide repeat.

Animals↗
PubMed1998

Histamine receptor antagonists, cyclooxygenase blockade, and tumor necrosis factor during acute septic insult.

Tumor necrosis factor (TNF) may be a major endogenous mediator of sepsis-induced acute organ injury. We proposed that treatment of septic pigs with the combined agents ibuprofen, a cyclooxygenase inhibitor, and histamine receptor antagonists, cimetidine (H2 antagonist) and diphenhydramine (H1 antagonist) would result in lower circulating levels of TNF and decreased parameters of sepsis-induced injury in these animals. To test this, plasma TNF activity, cardiac index, systemic and pulmonary arterial pressures, arterial PO2 and bronchoalveolar lavage protein content were monitored for 300 min in four groups of anesthetized pigs: saline-infused control pigs (n = 4); pigs infused for 60 min with Pseudomonas aeruginosa (5 x 10(8) organisms/mL, .3 mL/20 kg/min) (n = 5) and pigs infused for 60 min with P. aeruginosa plus ibuprofen (12.5 mg/kg) alone (n = 4) or ibuprofen plus cimetidine (150 mg) and diphenhydramine (30 mg/kg) at 0 and 120 min (CID, n = 4). Within 60 min, pigs infused with P. aeruginosa exhibited increased plasma TNF activity (>8-fold increase in ng/mL TNF; L929 cytolysis assay) and showed alterations in all hemodynamic and pulmonary parameters. Ibuprofen or CID administration in the septic pigs decreased peak TNF activity by 4.6 and 10.2 ng/mL, respectively, and CID treatment was correlated with better attenuation of certain sepsis-induced alterations. These results show that CID treatment attenuates sepsis-induced injury and that this is correlated with reduced plasma TNF activity in a porcine model of sepsis-induced acute organ injury.

Animals↗
PubMed1997

A medium-density genetic linkage map of the bovine genome.

A cattle genetic linkage map was constructed which covers more than 95 percent of the bovine genome at medium density. Seven hundred and forty six DNA polymorphisms were genotyped in cattle families which comprise 347 individuals in full sibling pedigrees. Seven hundred and three of the loci are linked to at least one other locus. All linkage groups are assigned to chromosomes, and all are orientated with regards to the centromere. There is little overall difference in the lengths of the bull and cow linkage maps although there are individual differences between maps of chromosomes. One hundred and sixty polymorphisms are in or near genes, and the resultant genome-wide comparative analyses indicate that while there is greater conservation of synteny between cattle and humans compared with mice, the conservation of gene order between cattle and humans is much less than would be expected from the conservation of synteny. This map provides a basis for high-resolution mapping of the bovine genome with physical resources such as Yeast and Bacterial Artificial Chromosomes as well as providing the underpinning for the interpolation of information from the Human Genome Project.

Animals↗
PubMed1997

The development and utility of a defined muscle and fat co-culture system.

The utility of co-culture systems in defining the interactions between two different cell types has been well documented in the literature but is a relatively new tool for use in the study of cells derived from normal muscle tissue from meat animals. The majority of myonuclei in postnatal skeletal muscle cells (myofibers) result from satellite cell proliferation, differentiation and fusion with existing myofibers. As such, satellite cell culture systems that mimic postnatal myofibers have great potential for delineating the process of growth and repair of muscle mass. Other ways to simulate the environment of postnatal myofibers might include the development of co-culture systems using satellite cells, or satellite cell-derived myotubes, and other mesodermal cells commonly found associated with muscle tissue in vivo. This brief review describes our initial efforts to develop a defined satellite cell and preadipocyte co-culture system. We provide useful information about defined media requirements and requirements for proper cell orientation and growth on two different growth planes. We present summary data to suggest that differences were found between members of the insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) families of polypeptides, when conditioned media samples were analyzed from co-cultures composed of 3T3-L1 preadipocytes and satellite cells (with different propensities to undergo morphological fusion to form multinucleated myotubes). We also provide information about potential problems to avoid when initiating and conducting co-culture experiments. Such a co-culture system has application in the study of human obesity and also in the regulation of fat deposition in meat animals.

Adipocytes↗
PubMed1997

Microsatellite evolution--a reciprocal study of repeat lengths at homologous loci in cattle and sheep.

The application of microsatellites in evolutionary studies requires an understanding of the patterns governing their evolution in different species. The finding that homologous microsatellite loci are longer, i.e., containing more repeat units, in human and in other primates has been taken as evidence for directional microsatellite evolution and for a difference in the rate of evolution between species. However, it has been argued that this finding is an inevitable consequence of biased selection of longer-than-average microsatellites in human, because cloning procedures are adopted to generate polymorphic and, hence, long markers. As a test of this hypothesis, we conducted a reciprocal comparison of the lengths of microsatellite loci in cattle and sheep using markers derived from the bovine genome as well as the ovine genome. In both cases, amplification products were longer in the focal species, and loci were also more polymorphic in the species from which they were originally cloned. The crossing pattern that we found suggests that interspecific length differences detected at homologous microsatellite loci are the result of biased selection of loci associated with cloning procedures. Hence, comparisons of microsatellite evolution between species are flawed unless they are based on reciprocal analyses or on genuinely random selection of loci with respect to repeat length.

Animals↗
PubMed1997

Genetic diversity of Asian water buffalo (Bubalus bubalis): microsatellite variation and a comparison with protein-coding loci.

Twenty-one microsatellite loci in 11 populations of Asian water buffalo (eight swamp, three river type) were analysed and, within and among populations, genetic variability was compared with results from 25 polymorphic protein-coding loci. Within-population mean heterozygosity ranged from 0.380-0.615, approximately twice that estimated from the protein-coding loci (0.184-0.346). Only eight significant departures from Hardy-Weinberg equilibrium (involving four loci) were detected; global tests showed significant heterozygote deficiencies for these four loci. Non-amplifying alleles are likely to be segregating in some or all populations for one of these loci, and probably for the other three. There was significant differentiation between the swamp and river types of water buffalo, and among populations within each buffalo type. Estimates of theta (measure of population differentiation) for each locus for the eight swamp populations were all highly significant (mean theta = 0.168 +/- 0.018). Mean theta for protein-coding loci was not significantly different (0.182 +/- 0.041). The variance among protein-coding loci was significantly higher than among microsatellite loci, suggesting balancing selection affecting allele frequencies at some protein-coding loci. Genetic distances show clear separation of the swamp and river types, which were estimated to have diverged at least 10,000-15,000 years ago. The topology of the swamp populations' microsatellite tree is consistent with their geographical distribution and their presumed spread through south-east Asia. By contrast, the tree based on the protein-coding loci distances is quite different, being clearly distorted by a bottleneck effect in one population, and possibly in at least two others. As many domestic livestock breeds are possibly descended from small numbers of founders, microsatellite-based trees are to be preferred in assessing breed genetic relationships.

Alleles↗
PubMed1996

Psychosocial functioning and quality of life in patients with primary brain tumors.

Perceived quality of life (QOL) was evaluated in a group of 50 patients with primary brain tumors. Participants completed two QOL measures and a demographic profile. Age was found not to be an important factor in differentiating QOL in these patients. All areas of QOL were found to be affected adversely by one or more of five factors: being female, being divorced, having bilateral tumor involvement, having received chemotherapy, and having a poor performance status. Pearson product-moment correlations conducted on the subscale and total scores of the two QOL instruments revealed that the two scales measure different QOL aspects and overlap in only a few areas. This may be related to the different measurement paradigms that these two instruments represent. This study is one of the first to evaluate the multidimensional aspects of QOL in patients with primary brain tumors, an understudied group. A prospective study of QOL in this group, already underway at the authors' institution, is needed to evaluate comprehensively the effect of different treatments and interventions on the QOL functioning of primary brain tumor patients. Additionally, this study shows that the choice of QOL instruments is very important and needs to be driven by the research question.

Adult↗
PubMed1995

Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation.

PURPOSE: Cognitive deficits after treatment for small cell lung cancer (SCLC) have been attributed to prophylactic cranial irradiation (PCI). A prospective study of neuropsychological function was undertaken to document the evolution and magnitude of neuropsychologic deficits. METHODS AND MATERIALS: Thirty patients with limited stage SCLC who responded well (29 complete response (CR), 1 partial response (PR)) to combination chemotherapy plus thoracic irradiation or resection were studied with neuropsychological tests in the cognitive domains of intelligence, frontal lobe function, language, memory, visual-perception, and motor dexterity prior to a planned course of PCI. Nine patients had a neurologic history that could influence testing. RESULTS: An unexpected 97% (29 out 30) of patients had evidence of cognitive dysfunction prior to PCI. The most frequent impairment was verbal memory, followed by frontal lobe dysfunction, and fine motor incoordination. Of the patients with no prior neurologic or substance abuse history, 20 out of 21 (95%) had impairments on neuropsychological assessment. This neurologically normal group was just as impaired as the group with such a history with respect to delayed verbal memory and frontal lobe executive function. Eleven patients had neuropsychological testing 6 to 20 months after PCI; no significant differences were found from their pretreatment tests. CONCLUSIONS: A high proportion of neurologically normal patients was limited SCLC and favorable responses to combination chemotherapy have specific cognitive deficits before receiving PCI. Short-term (6 to 20 months) observations after PCI have shown no significant deterioration.

Adult↗
PubMed1995

A set of polymorphic DNA microsatellites useful in swamp and river buffalo (Bubalus bubalis).

DNA microsatellites have found widespread application in gene mapping, pedigree determination and population genetics. In closely related species such as bovids, heterologous polymerase chain reaction (PCR) primers may in some cases be used, bypassing the need to isolate and characterize microsatellite-containing sequences and design PCR primers. We report on the ability of a set of eighty bovine derived DNA microsatellite primers to amplify sequences in the two types (swamp and river) of water buffalo (Bubalus bubalis). Number of alleles and per cent heterozygosities in a large number of animals were determined on a subset of microsatellite loci selected on the robustness of the primers. These loci will form the basis of a set of polymorphic DNA markers for use in water buffalo.

Alleles↗
PubMed1995

Discovery, biosynthesis, and mechanism of action of the zaragozic acids: potent inhibitors of squalene synthase.

The zaragozic acids (ZAs), a family of fungal metabolites containing a novel 4,6,7-trihydroxy-2,8-dioxobicyclo[3.2.1]octane-3,4,5-tricarboxylic acid core, were discovered independently by two separate groups screening natural product sources to discover inhibitors of squalene synthase. This family of compounds all contain the same core but differ in their 1-alkyl and their 6-acyl side chains. Production of the ZAs is distributed over an extensive taxonomic range of Ascomycotina or their anamorphic states. The zaragozic acids are very potent inhibitors of squalene synthase that inhibit cholesterol synthesis and lower plasma cholesterol levels in primates. They also inhibit fungal ergosterol synthesis and are potent fungicidal compounds. The biosynthesis of the zaragozic acids appears to proceed through alkyl citrate intermediates and new members of the family have been produced through directed biosynthesis. These potent natural product based inhibitors of squalene synthase have potential to be developed either as cholesterol lowering agents and/or as antifungal agents.

Animals↗
PubMed1994

Characterization of 65 bovine microsatellites.

Microsatellites or simple sequence repeat (SSR) polymorphisms are used widely in the construction of linkage maps in many species. High levels of polymorphism coupled with the ease of analysis of the polymerase chain reaction (PCR) have resulted in this type of maker being one of the most widely used for genetic analysis. In this paper we describe 58 polymorphic bovine microsatellites that were isolated from insert size selected bovine genomic libraries. Primer sequences, number of alleles, and heterozygosity levels in cattle reference families are reported. Chromosomal locations for 47 of these microsatellites as well as for 7 previously described systems derived from entries in the Genbank or EMBL databases have been determined. The markers map to 24 syntenic or chromosomal locations. Polymorphic bovine microsatellites were estimated to occur, on average, every 320 kb, and there is no evidence of clustering in the genome. Thirty of the bovine-derived microsatellite systems gave specific and polymorphic products in sheep, adding to the number of useful markers in that species.

Animals↗
PubMed1994

Induction of major heat-shock proteins of Saccharomyces cerevisiae, including plasma membrane Hsp30, by ethanol levels above a critical threshold.

Many of the changes induced in yeast by sublethal yet stressful amounts of ethanol are the same as those resulting from sublethal heat stress. They include an inhibition of fermentation, increased induction of petites and stimulation of plasma membrane ATPase activity. Ethanol, at concentrations (4-10%, v/v) that affect growth and fermentation rates, is also a potent inducer of heat-shock proteins including those members of the Hsp70 protein family induced by heat shock. This induction occurs above a threshold level of about 4% ethanol, although different heat-shock proteins and heat-shock gene promoters are optimally induced at different higher ethanol levels. In addition ethanol (6-8%) causes the same two major changes to integral plasma-membrane protein composition that result from a sublethal heat stress, reduction in levels of the plasma membrane ATPase protein and acquisition of the plasma membrane heat-shock protein Hsp30.

Adenosine Triphosphatases↗
PubMed1994

Evaluation of the neurobehavioral functioning of patients before, during, and after bone marrow transplantation.

PURPOSE: To evaluate the cognitive and emotional functioning of patients undergoing bone marrow transplantation (BMT) in the protected environment (PE). PATIENTS AND METHODS: Patients were given tests of cognition and mood before their hospitalization in the PE, after 2 weeks, at discharge, and at 8 months post-BMT. Locus of control, degree of social support, previous biotherapy, and on-treatment psychiatric consultation were also analyzed. RESULTS: Before BMT, 20% of patients had mild cognitive dysfunction, and nearly 40% had significant anxiety. Although few patients developed problems with cognition or mood during the study, short-term memory deficits nearly doubled at follow-up compared with baseline. Anxiety decreased significantly during hospitalization and remained low at follow-up. In contrast, depression increased throughout hospitalization, but decreased at follow-up. Pre-BMT emotional status and cognitive functioning were highly related to long-term outcome. Type of BMT, locus of control, and degree of social support were related to psychologic distress and cognitive functioning, both during and after BMT. Patient age was not a predictor of neurobehavioral symptoms during or after BMT. CONCLUSION: Pretransplant emotional and cognitive functioning are important determinants of long-term outcome and quality of life (QOL) in BMT patients. In addition, a few patients undergoing BMT develop short-term memory difficulties and mood disturbance that may persist. Pretransplant identification of patients at risk for neurobehavioral difficulties may guide early interventions during hospitalization. Posttransplant assessment may then be used to develop rehabilitation programs and other interventions for individuals with persisting complaints.

Adult↗
PubMed1994

Gangrenous streptococcal myositis: case report.

Streptococcal infection of the large skeletal muscles is a rare but often rapidly fatal condition that may occur for no apparent reason. Nonsteroidal anti-inflammatory drugs may have an adverse effect on outcome. A high index of suspicion is the key to early diagnosis.

Adolescent↗