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Biomedical subjects

M J Gordon

Publications and source records attributed to M J Gordon.

At least 37 records · Page 2Linked to original sources
PubMed1996

Prevalence and origin of de novo duplications in Charcot-Marie-Tooth disease type 1A: first report of a de novo duplication with a maternal origin.

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. Sporadic cases of CMT have been described since the earliest reports of the disease. The most frequent form of the disorder, CMT1A, is associated with a 1.5-Mb DNA duplication on chromosome 17p11.2, which segregates with the disease. In order to investigate the prevalence of de novo CMT1A duplications, this study examined 118 duplication-positive CMT1A families. In 10 of these families it was demonstrated that the disease had arisen as the result of a de novo mutation. By taking into account the ascertainment of families, it can be estimated that > or = 10% of autosomal dominant CMT1 families are due to de novo duplications. The CMT1A duplication is thought to be the product of unequal crossing over between parental chromosome 17 homologues during meiosis. Polymorphic markers from within the duplicated region were used to determine the parental origin of these de novo duplications in eight informative families. Seven were of paternal and one of maternal origin. This study represents the first report of a de novo duplication with a maternal origin and indicates that it is not a phenomenon associated solely with male meioses. Recombination fractions for the region duplicated in CMT1A are larger in females than in males. That suggests that oogenesis may be afforded greater protection from misalignment during synapsis, and/or that there may be lower activity of those factors or mechanisms that lead to unequal crossing over at the CMT1A locus.

Charcot-Marie-Tooth Disease↗
PubMed1995

Plasma membrane fatty-acid-binding protein in human placenta: identification and characterization.

A plasma membrane fatty-acid-binding protein (FABPpm) with a molecular mass of approximately 40 kDa has been identified in human placenta. Binding of both [14C] oleate and [14C] linoleate to human placental membranes was found to be time and temperature dependent. Sulphobromophthalein and alpha-tocopherol did not show competition with the [14C] fatty acid binding. These data suggest that the binding sites are specific for fatty acids. incubation of the membranes with trypsin reduced fatty acid binding activity, indicating that the binding sites were protein in nature. A FABPpm was then solubilized from placental membranes and purified to electrophoretic homogeneity. The fatty acid binding activity of the purified protein was confirmed by autoradioblotting. Polyclonal antiserum raised to FABPpm reduced fatty acid binding to placental membrane significantly compared with preimmune serum. The pI value and the amino acid composition of the protein suggest that the placental FABPpm is different from the previously identified hepatic FABPpm.

Amino Acids↗
PubMed1995

Characterization of a novel alpha-tocopherol-binding protein from bovine heart cytosol.

We previously reported the identification of a new alpha-tocopherol-binding protein (approximately 15 kDa) in the cytosol of rat liver and heart and in rabbit heart (A.K. Dutta-Roy et al., J. Nutr. Biochem. 5, 562-570, 1994). This protein specifically binds alpha-tocopherol and enhances its transfer between separate membranes. In the present paper we have purified and characterized the alpha-tocopherol-binding protein from bovine heart cytosol and compared its various structural and functional properties with the similar size (approximately 15 kDa) cytosolic fatty acid-binding protein of this tissue. alpha-Tocopherol-binding protein was purified to electrophoretic homogeneity from bovine heart cytosol by a procedure involving precipitation with 70% ammonium sulfate, followed sequentially by gel filtration chromatography and chromatofocusing. The purified protein migrated as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular mass of 16 kDa. Isoelectric focusing of the purified protein showed that the pI value is around 4.5. The binding of alpha-tocopherol to the purified protein was rapid, reversible, and saturable. The alpha-tocopherol-binding protein did not bind oleate as assessed by direct radiolabeled fatty acid binding and fluorescence enhancement assay. Amino acid analysis showed the presence of a large number of Ala, Gly, Ser, Lys, and Pro residues and a lesser number of aromatic residues in this protein. Anti-bovine heart fatty acid-binding protein antibody did not recognize the alpha-tocopherol-binding protein in the Western blot. The Western blot, ligand affinity, molecular size, and amino acid analysis data suggest that the alpha-tocopherol-binding protein is different from the cytosolic fatty acid-binding protein and that it may be involved in intracellular transport and metabolism of alpha-tocopherol.

Animals↗
PubMed1994

Plasma membrane fatty acid-binding protein (FABPpm) of the sheep placenta.

Fatty acid-binding protein (FABPpm) has been identified and characterised from sheep placental membranes. Binding of [14C]oleate to placental membranes was found to be time- and temperature-dependent. Addition of a 20-fold excess unlabelled oleic, palmitic, or linoleic acid reduced the binding of [14C]oleate to the membranes to around 50% of total binding, whereas D-alpha-tocopherol at similar concentrations did not affect [14C]oleate binding. This indicates that the binding sites are specific to fatty acids. Specific binding of [14C]oleate was reduced by heat denaturation or trypsin digestion of the membranes, suggesting that the fatty acid-binding sites are protein in nature. FABPpm was then solubilised from sheep placental membranes, and subsequently purified to electrophoretic homogeneity using an oleate-agarose affinity column. The purified FABPpm had an apparent molecular mass of 40 kDa, as determined by SDS-PAGE and by gel permeation chromatography. The [14C]oleate-binding activity of the purified protein was also confirmed by PAGE followed by autoradioblotting. The specific binding for oleate was around 1.5 nmol per mg of membrane protein. Our data indicate the presence of FABPpm in sheep placental membranes.

Animals↗
PubMed1993

Identification of a low molecular mass (14.2 kDa) alpha-tocopherol-binding protein in the cytosol of rat liver and heart.

An alpha-tocopherol-binding protein (TBP) with a molecular mass of 14.2 kDa has been identified from the cytosol of rat heart and liver and purified to electrophoretic homogeneity by precipitation with 70% ammonium sulphate, followed by gel filtration and ion-exchange chromatography. In addition to the 14.2 kDa TBP, liver also contains the previously described 30 kDa TBP. The concentrations of the 14.2 kDa TBP in heart and liver were 12.3 micrograms and 17.5 micrograms per g of tissue, respectively. The purified protein specifically binds d alpha-tocopherol in preference to the delta- and gamma-homologues but does not bind oleate. The TBP stimulated the transfer of d alpha-tocopherol from liposomes to mitochondria in vitro by 8-10 fold. These results suggest that low molecular mass TBPs may play a role in intracellular vitamin E transport.

Animals↗
PubMed1992

Percutaneous localization of pulmonary nodules for thoracoscopic lung resection.

A limiting factor in removing pulmonary nodules by videothoracoscopic techniques is the inability to locate lesions deep within the substance of the lung. We describe a technique in which a hook wire commonly used to localize nonpalpable breast lesions is placed percutaneously into the lung nodule preoperatively. Using the wire anchored into the lung as a guide, the target lesion can be successfully identified and removed thoracoscopically.

Humans↗
PubMed1992

The effects of propionate and butyrate on acetate metabolism in rat hepatocytes.

1. Two mM propionate or butyrate inhibited the mitochondrial uptake of acetate by rat hepatocytes. 2. With propionate the inhibition was so strong that the net formation of acetate in the cytoplasm, usually masked by the mitochondrial uptake, appeared directly as a net output of acetate into the medium; showing that this net formation of acetate, reported by [Crabtree B., Gordon M.-J. and Christie S. L. (1990) Biochem. J. 270, 219-225] is not an artefact arising from a misinterpretation of isotopic data. 3. The results also suggest that propionate and butyrate inhibit peroxisomal metabolism.

Acetates↗
PubMed1992

Self-assessment programs and their implications for health professions training.

Although expected of all health professionals, self-assessment skills are seldom addressed directly in training. A previous review by the author identified curricular criteria associated with improved accuracy and validity in self-assessments of knowledge and performance in curriculum studies published between January 1970 and February 1990. The present review analyzed 11 studies that meet those criteria. Eight studies were of implementations of self-assessment components within training programs in the health professions, and three involved other training environments. Most described initial disorientation or opposition on the part of learners, attributed to unfamiliar roles and to learners' distrust. The curricula that successfully negotiated the transition to self-assessment norms reported noncognitive benefits such as improvements in morale, motivation, and communications among learners and faculty. Reported cognitive benefits included improvements in knowledge, performance, and self-analysis of performance. The constellation of effects suggests that effective self-assessment programs may promote more mature, collegial, and productive learning environments, particularly suited to the training of health professionals. Most curricula fostering effective self-assessment did not require extraordinary resources, and none jeopardized traditional standards. No evidence was found to support or challenge the expectation that self-assessment training would transfer to later work settings.

Health Occupations↗
PubMed1991

Protocol for resolving protein mixtures in capillary zone electrophoresis.

The separation of protein mixtures by capillary zone electrophoresis can be plagued by wall adsorption of the protein components, causing peak broadening and distortion. A method is presented for overcoming this problem by adding ethylene glycol to the protein sample and by choosing the running buffer and protein sample to be at different pH values and molarities. This protocol appears to work for a wide class of proteins having different molecular weights and pI values. The method has been applied to the analysis of proteins in human serum. Compared to the traditional method of agarose gel electrophoresis, the present method is more rapid and offers better resolution, suggesting its potential as a clinical diagnostic of certain disease states.

Blood Proteins↗
PubMed1991

A review of the validity and accuracy of self-assessments in health professions training.

Valid self-assessment is fundamental to continuing professional competence but is seldom explicitly taught in health professions training. This review analyzed 18 scholarly articles published between January 1970 and February 1990 (14 articles regarding health professions trainees, and four concerning college students or graduate trainees) in which it was possible to compare performance as self-assessed by trainees with performance as assessed by experts or objective tests. The validity of self-assessed performance was found to be low to moderate and did not improve with time in conventional health professions training programs. Self-assessed performance seemed closely related to generalized self-attributions and was minimally influenced by external feedback in the form of test scores, grades, or faculty assessments. In five programs emphasizing explicit self-assessment goals and training strategies, moderate-to-high validity outcomes or improvements over time were demonstrated. Much of what passes for self-assessment in training seems the exercise of an underdeveloped skill, but effective training to improve validity and accuracy is available and feasible.

Health Personnel↗
PubMed1991

A collaborative approach to a primary care preclinical preceptorship for underserved settings.

This study describes the first few years of a collaborative effort undertaken by the University of Washington School of Medicine (UWSM), the Washington-Alaska-Montana-Idaho (WAMI) Area Health Education Center program, the Washington Academy of Family Practice, and the Family Health Foundation of Washington to provide students with an early introduction to primary care practice in rural and urban underserved settings. Starting in 1988, these collaborators organized a summer preceptorship that offered placements in the WAMI region to 23 student volunteers who were between their first and second years at the UWSM in 1989 and to 51 such students in 1990. A preliminary evaluation of the program indicated that the students (73 of whom participated in the evaluation) were extremely satisfied with the program's ability to provide them with firsthand exposure to community medicine. In conclusion, the authors discuss the advantages of collaboration and make suggestions for identifying potential educational partners.

Alaska↗
PubMed1991

Acute airway injury during high-frequency jet ventilation and high-frequency oscillatory ventilation.

BACKGROUND AND METHODS: We compared tracheal histologic injury patterns, airway pressure (Paw) requirements, and in vivo and in vitro estimate of airway humidification in 13 adult cats with normal lungs mechanically ventilated for 16 hr. Six animals were treated with high-frequency jet ventilation at 400 breaths/min and seven animals with high-frequency oscillatory ventilation at 900 breaths/min. RESULTS: Peak airway pressure, Paw, mean Paw, and end-expiratory pressure requirements were significantly higher for high-frequency oscillatory ventilation as compared with high-frequency jet ventilation for similar gas exchange (p less than .01). While in vivo estimates of airway humidification suggested progressively greater H2O delivery into the respirator circuit, and therefore the airway, with higher frequencies, the in vitro study suggested similar relative humidities of the delivered gases during both types of mechanical ventilation. Tracheal injury, measured using a semiquantitative scoring system, was scored similarly for both ventilators studied despite the higher pressure requirements seen with the high-frequency oscillator. CONCLUSIONS: In this animal model, high-frequency ventilation using either jet or oscillation techniques produced similar inflammatory tracheal damage despite differences in Paw exposure and humidity.

Air Pressure↗
PubMed1990

Measurement of the rates of acetyl-CoA hydrolysis and synthesis from acetate in rat hepatocytes and the role of these fluxes in substrate cycling.

1. Acetyl-CoA hydrolysis, acetyl-CoA synthesis from acetate and several related fluxes were measured in rat hepatocytes. 2. In contrast with acetyl-CoA hydrolysis, most of the acetyl-CoA synthesis from acetate occurred in the mitochondria. 3. Acetyl-CoA hydrolysis was not significantly affected by 24 h starvation or (-)-hydroxycitrate. 4. In the cytoplasm there was a net flux of acetyl-CoA to acetate, and substrate cycling between acetate and acetyl-CoA in this compartment was very low, accounting for less than 0.1% of the total heat production by the animal. 5. A larger cycle, involving mitochondrial and cytoplasmic acetate and acetyl-CoA, may operate in fed animals, but would account for only approx 1% of total heat production. 6. It is proposed that the opposing fluxes of mitochondrial acetate utilization and cytoplasmic net acetate production may provide sensitivity, feedback and buffering, even when these fluxes are not linked to form a conventional substrate cycle.

Acetates↗