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Biomedical subjects

K Hunter

Publications and source records attributed to K Hunter.

At least 19 recordsLinked to original sources
PubMed1997

High-resolution linkage map of mouse chromosome 13 in the vicinity of the host resistance locus Lgn1.

Natural resistance of inbred mouse strains to infection with Legionella pneumophila is controlled by the expression of a single dominant gene on chromosome 13, designated Lgn1. The genetic difference at Lgn1 is phenotypically expressed as the presence or absence of intracellular replication of L. pneumophila in host macrophages. In our effort to identify the Lgn1 gene by positional cloning, we have generated a high-resolution linkage map of the Lgn1 chromosomal region. For this, we have carried out extensive segregation analysis in a total of 1270 (A/J x C57BL/6J) x A/J informative backcross mice segregating the resistance allele of C57BL/6J and the susceptibility allele of A/J. Additional segregation analyses were carried out in three preexisting panels of C57BL/6J x Mus spretus interspecific backcross mice. A total of 39 DNA markers were mapped within an interval of approximately 30 cM overlapping the Lgn1 region. Combined pedigree analyses for the 5.4-cM segment overlapping Lgn1 indicated the locus order and the interlocus distances (in cM): D13Mit128-(1.4)-D13Mit194-(0.1)-D13Mit147-(0.9)-D13 Mit36-(0.9)-D13Mit146-(0.2)-Lgn1/D13Mit37-(1.0)- D13Mit70. Additional genetic linkage studies of markers not informative in the A/J x C57BL/6J cross positioned D13Mit30, -72, -195, and -203, D13Gor4, D13Hun35, and Mtap5 in the immediate vicinity of the Lgn1 locus. The marker density and resolution of this genetic linkage map should allow the construction of a physical map of the region and the isolation of YAC clones overlapping the gene.

Animals↗
PubMed1996

"Don't think zebras": uncertainty, interpretation, and the place of paradox in clinical education.

Working retrospectively in an uncertain field of knowledge, physicians are engaged in an interpretive practice that is guided by counterweighted, competing, sometimes paradoxical maxims. "When you hear hoofbeats, don't think zebras," is the chief of these, the epitome of medicine's practical wisdom, its hermeneutic rule. The accumulated and contradictory wisdom distilled in clinical maxims arises necessarily from the case-based nature of medical practice and the narrative rationality that good practice requires. That these maxims all have their opposites enforces in students and physicians a practical skepticism that encourages them to question their expectations, interrupt patterns, and adjust to new developments as a case unfolds. Yet medicine resolutely ignores both the maxims and the tension between the practical reasoning they represent and the claim that medicine is a science. Indeed, resolute epistemological naivete is part of medicine's accommodation to uncertainty; counterweighted, competing, apparently paradoxical (but always situational) rules enable physicians simultaneously to express and to ignore the practical reason that characterizes their practice.

Art↗
PubMed1996

Generation and mapping of Mus spretus strain-specific markers for rapid genomic scanning.

We describe here a set of genetic markers, based on IRS-PCR amplification difference, that are specifically designed for efficient, high throughput genetic mapping in [(M. domesticus x wild-derived) F1 x M. domesticus] interspecific backcrosses. 146 new genetic loci have been mapped, and strain distribution for these markers has been determined in 96 mouse strains. 103 (81%) of 127 tested markers are present only in one or more wild-derived strains, but absent in 76 other commonly used strains, demonstrating their utility in a variety of mouse pair combinations. Because of the ease of genotyping with this marker set, rapid genome scans for complex genetic trait loci involving crosses between wild-derived strains and other commonly used strains can now be carried out efficiently with large numbers of animals.

Animals↗
PubMed1996

Protein synthesis rates of skeletal muscle, lymphocytes, and albumin with stress hormone infusion in healthy man.

The rate of protein synthesis was assessed in muscle, lymphocytes, and albumin in healthy volunteers administered an infusion of 6.0 micrograms cortisol +3.0 ng glucagon +0.5 nmol epinephrine min-1.kg-1. Protein synthesis in muscle tissue was not sensitive to the immediate effects of hormone infusion, but decreased significantly by 18 hours after the infusion had ceased (1.77% +/- 0.12% per day v 1.29% +/- 0.10%, P < .05). The rate of protein synthesis in lymphocytes was acutely sensitive to the effect of the hormone infusion, decreasing from 7.15% +/- 1.02% per day to 2.47% +/- 0.5% (P < .05). However, measurements made 18 hours after the end of the hormone infusion indicated that lymphocyte protein synthesis returned to the preinfusion rates. The rate of albumin synthesis was unaltered during infusion of the stress hormones, but was significantly increased when measured 18 hours after ending the hormone infusion (6.84% +/- 0.43% per day v 7.99% +/- 0.45%, P < .05). Thus, tissues respond differently to stress hormone infusion, demonstrating the importance of studying multiple organ systems when assessing the regulation of protein metabolism.

Adult↗
PubMed1996

Genetic mapping of a pulmonary adenoma resistance (Par1) in mouse.

Lung cancer, a major cause of death in the Western world, has a poor prognosis. So far, therapeutic strategies have had only a limited effect. Lung cancer risk is strongly associated with cigarette smoking and lung cancer pedigrees are rare. However, a possible polygenic nature of inherited predisposition to this cancer has been envisaged. Mouse inbred strains with inherited predisposition and resistance to lung cancer provide an important tool for the dissection of the genetics of this complex disease. The A/J strain carries the pulmonary adenoma susceptibility 1 (Pas1) locus and develops many lung tumours. We have mapped the M. spretus-derived locus that strongly resists the lung tumorigenesis in Pas1/+ mice. This locus, pulmonary adenoma resistance 1 (Par1) maps to mouse chromosome 11, near the Rara locus, with a lod score of 5.3. In Pas1/+ mice Par1 accounts for 23% of the phenotypic variance and 10 fold reduction in total tumour volume. These results provide evidence for a major resistance locus affecting the expression of an inherited predisposition to lung cancer.

Adenoma↗
PubMed1995

Efficient high-resolution genetic mapping of mouse interspersed repetitive sequence PCR products, toward integrated genetic and physical mapping of the mouse genome.

The ability to carry out high-resolution genetic mapping at high throughput in the mouse is a critical rate-limiting step in the generation of genetically anchored contigs in physical mapping projects and the mapping of genetic loci for complex traits. To address this need, we have developed an efficient, high-resolution, large-scale genome mapping system. This system is based on the identification of polymorphic DNA sites between mouse strains by using interspersed repetitive sequence (IRS) PCR. Individual cloned IRS PCR products are hybridized to a DNA array of IRS PCR products derived from the DNA of individual mice segregating DNA sequences from the two parent strains. Since gel electrophoresis is not required, large numbers of samples can be genotyped in parallel. By using this approach, we have mapped > 450 polymorphic probes with filters containing the DNA of up to 517 backcross mice, potentially allowing resolution of 0.14 centimorgan. This approach also carries the potential for a high degree of efficiency in the integration of physical and genetic maps, since pooled DNAs representing libraries of yeast artificial chromosomes or other physical representations of the mouse genome can be addressed by hybridization of filter representations of the IRS PCR products of such libraries.

Animals↗
PubMed1995

Assessment of skeletal muscle viability by PET.

UNLABELLED: We investigated the use of [18F]fluoro-2-deoxyglucose (FDG) PET scanning for assessment of skeletal muscle viability in patients with peripheral vascular disease and in patients following free-flap skeletal muscle transfer for closure of open wounds. METHODS: We obtained 32 FDG-PET scans from 30 patients, either at the time of admission for peripheral vascular disease (n = 16) or between 1 and 15 days after surgery for skeletal muscle transfer (n = 16). Ratios between injured and contralateral limb FDG tracer activity uptake were correlated with clinical outcome at 1 mo to 3 yr follow-up. RESULTS: Viable muscle uptake ratios ranged from 0.47 to 7.88 (mean: 2.26 +/- 1.81; n = 26), while nonviable muscle uptake ratios ranged from 0.12 to 0.46 (mean: 0.27 +/- 0.12; n = 6; p < 0.02). After skeletal muscle transfer, two patients with viable tissue, as documented by PET, required amputation due to osteomyelitis, and one patient with peripheral vascular disease who showed viable tissue by PET required amputation 3 mo after the PET scan because of recurrent ulcers. CONCLUSION: FDG-PET scanning can determine skeletal muscle viability in patients with peripheral vascular disease and in patients following free-flap transfer.

Adolescent↗
PubMed1994

IRE-bubble PCR: a rapid method for efficient and representative amplification of human genomic DNA sequences from complex sources.

A significant issue in the analysis of any genomic DNA segment is the generation of a unique set of short single-copy sequences that are representative of that region. In this report we describe a novel technique, IRE-bubble PCR, which was designed to amplify the human DNA content of somatic cell hybrids, YACs, cosmids, and lambda phage and result in greater complexity and representation than standard inter-IRE PCR. Here we demonstrate that IRE-bubble PCR is species specific and that it results in the generation of a product that is at least 10-fold more complex and representative than that produced by standard inter-IRE PCR. In addition, we have addressed the factors that contribute to the representation of the IRE-bubble PCR product and show how they may be used to further increase the complexity of this reaction. Finally, we have illustrated how the complexity and distribution of products generated by IRE-bubble PCR can be exploited and applied to FISH mapping and "chromosome painting" as well as to the generation of STSs targeted to specific chromosomal or subchromosomal regions.

Animals↗
PubMed1994

The mouse Fas-ligand gene is mutated in gld mice and is part of a TNF family gene cluster.

The gene for the mouse Fas ligand was cloned and its chromosomal position determined. Fasl was tightly linked to gld (no crossovers in 567 meiotic events) on mouse chromosome 1 and closely linked with a novel member of the same TNF family of ligands, the Ox40 ligand (Ox40l, 1 crossover in 567 meiotic events). Southern blot analysis did not reveal any difference between the Fasl gene from gld and wild-type mice and levels of Fasl mRNA transcripts were similar in PMA and ionomycin induced wild-type and coisogenic gld T cells. Sequence analysis of the gld gene indicated a single amino acid change (Phe Leu) in the COOH terminal portion of this type II transmembrane protein, and COS cells transfected with Fasl cDNA from gld mice failed to induce apoptosis of Fas-expressing target cells. Thus, the data demonstrate that the gld phenotype is the result of a point mutation in the Fasl gene and that Fasl is part of a complex of ligands structurally related to TNF mapping within a small region of mouse chromosome 1.

Amino Acid Sequence↗
PubMed1994

Sequential positron emission tomographic evaluations of brain metabolism in acute herpes encephalitis.

This first known positron emission tomography report on metabolic changes in acute herpes simplex virus (HSV-1) encephalitis demonstrates focal hypermetabolism in areas of cerebral cortex adjacent to actively inflamed hippocampus acutely infected with HSV-1. When neuropsychiatric symptoms recurred in a previously healthy 61-year-old patient 1 month after recovering from acute HSV-1 encephalitis, repeat positron emission tomography with fluorodeoxyglucose was helpful in ruling out recurrent active infection by showing marked hypometabolism throughout the previously infected temporal lobe.

Acute Disease↗
PubMed1994

Evidence that carbon monoxide is a mediator of critical illness.

We have measured arterial carboxyhemoglobin levels as an indicator of endogenous carbon monoxide production in 32 consecutive admissions to our Surgical Intensive Care Unit. A severity of illness score (APACHE II) was determined for each patient at the same time that blood was drawn. An increase in the APACHE II score indicates a worsening of the patient's condition. There was a positive correlation between arterial carboxyhemoglobin levels and the APACHE II score (p < 0.005). An increase in the white blood cell count indicates an increase in the severity of illness. Carboxyhemoglobin levels correlated with an increase in the white blood cell count to greater than the normal maximum count of 10.5 x 10(3) cells/mm3 within a 24 hour period (p < 0.05). These findings support our hypothesis that endogenously produced carbon monoxide may play a role in the pathogenesis of critical illness.

Carbon Monoxide↗
PubMed1993

Objective decision-making following a portal film: the results of a pilot study.

PURPOSE: To discriminate between random and systematic treatment setup errors using portal films. METHODS AND MATERIALS: A bi-dimensional analytic techniques using multiple analyses of variance based on Hotelling's T2 statistics to derive numerical and graphical measures of daily portal film accuracy and precision has been trialed using 88 daily portal films from seven patients' treatment. RESULTS: A demonstration is provided of how a reasonable approximation of random variation from the intended (Simulator) field center, and systematic displacement of the mean position of the portal film centers may be derived from a minimum number of portal films. If a random error as great as 10 mm exists, at least six or seven portal films are considered necessary to reliably detect and quantify the size of a systematic error. CONCLUSION: Our results suggest that a modest systematic error could go undetected until the end of a 5 or 6 week course of treatment if only one portal film is obtained each week. A greater number of portal films should be performed during the first week of treatment to reduce the frequency of such errors. Efforts to separate and quantify both random and systematic errors in setup are worthwhile and will lead to improvements in outcome at the individual patient level and at a departmental level in the development of quality assurance programs.

Humans↗