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Biomedical subjects

R A McPherson

Publications and source records attributed to R A McPherson.

11 recordsLinked to original sources

Data sharing and evaluation.

Interinstitutional evaluations of molecular markers for the diagnosis and staging of cancer are highly dependent on strict standardization of assays to make clinical comparisons valid. New assays for cancer markers depend on discoveries of biochemical or cellular functions coupled with technologies suitable for making relevant measurements. Transfer of these technologies from the research laboratory to the diagnostic laboratory requires method validation that consists of specific information regarding assay principle, reagents, calibration, sensitivity, assay behavior, specimen requirements, clinical and method correlations, reference range, quality control, proficiency testing, critical steps, and guidelines for interpretation. Fulfillment of all the components of method validation will guarantee the fastest and most accurate implementation of new diagnostic assays in clinical studies and practice.

Diffusion of Innovation

Rotational diffusion of the erythrocyte integral membrane protein band 3: effect of hemichrome binding.

Human erythrocyte band 3 was covalently labeled within the integral membrane domain by incubating intact erythrocytes with the phosphorescent probe eosinyl-5-maleimide. The rotational diffusion of band 3 in membranes prepared from these labeled cells was measured using the technique of time-resolved phosphorescence anisotropy. Three rotational correlation times ranging from 16 to 3800 microseconds were observed, suggesting that band 3 exists in different aggregate states within the plane of the membrane. The oxidizing agent phenylhydrazine was used to induce hemichrome formation within intact erythrocytes. The immobilization of band 3 in membranes prepared from these erythrocytes suggests that the binding of hemichromes induces clustering of band 3. The addition of purified hemichromes to erythrocyte ghosts leads to a similar effect. We have also examined the mobility of the cytoplasmic domain of band 3. This region was labeled indirectly using a phosphorescently labeled antibody which binds to an epitope within the cytoplasmic domain. We observed very rapid motion of the cytoplasmic region of band 3, which was only partially restricted upon hemichrome binding. This suggests that the integral and cytoplasmic domains of band 3 may be independently mobile.

Anion Exchange Protein 1, Erythrocyte

Update of autoantibodies in neurologic disease.

Many neurologic disorders recently have been discovered to have an autoimmune basis with autoantibodies that are responsible for neurologic symptoms and progression of the disease. Diagnosis and treatment of these disorders are facilitated by detection and monitoring of several autoantibodies. Some tumors express protein antigens shared by neurons, and an antitumor immune response leads to autoimmune antineuronal reactions exemplified by "paraneoplastic cerebellar degeneration." Other antibodies react with gangliosides present in many locations of the nervous system, leading to motor neuron damage and polyneuropathy. Phospholipid antibodies indirectly cause neurologic syndrome largely through thrombosis of cerebral vessels; other autoantibodies also have associations with specific neurologic symptoms.

Animals

Correlation of the effects of dexamethasone administration on urinary 17-ketosteroid and serum androgen levels in patients with hirsutism.

Total 24 hour urinary 17-ketosteroid and serum testosterone (T), androstenedione (delta), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DS), and cortisol levels were measured before and during four days of dexamethasone administration in 28 hirsute patients and 10 women with normal ovulatory cycles. Both the base-line urinary 17-ketosteroids and serum androgen levels were significantly higher (p less than 0.05) in hirsute than in normal subjects. Cortisol levels were similar in the two groups. Dexamethasone administration resulted in a significant suppression (p less than 0.05) of all the urinary and serum androgen and cortisol levels in both groups. At the end of suppression the serum DHEA, DS and cortisol levels were similar, while the urinary 17-ketosteroids and serum T and delta levels were still significantly higher (p less than 0.05) in the hirsute than in normal women. There was poor correlation between total urinary 17-ketosteroid and serum androgen results. These finding suggest there is a dual abnormality of androgen production in hirsute patients. The adrenal glands appear to secrete increased quatities of DHEA and DA, while the ovaries appear to produce elevated amounts of T and delta.

17-Ketosteroids

Coagulopathy in amyloidosis: combined deficiency of factors IX and X.

Combined severe deficiencies of blood clotting factors IX and X were observed in 2 patients who suffered from systemic amyloidosis. This unique deficiency state was marked by refractoriness to Vitamin K as well as to transfusion therapy. Increased antithrombin activity was present in both individuals and corresponded in time to the emergence of a monoclonal IgG kappa light chain paraprotein in 1. Both patients demonstrated profound bleeding disorders. It is hypothesized that the Vitamin K dependent factors have special affinity for amyloid deposits due to an unusual amino acid (gamma-carboxyglutamic acid) present in these factors.

Adult

Thromboembolism in Hageman trait.

The case of a patient with severe deficiency of Hageman factor (factor XII) in whom a thrombus embolized to arteries in a lower extremity is described. In addition to its action in intiating blood clotting through the intrinsic pathway, Hageman factor can influence kinin generation, fibrinolysis, and activation of complement. While individuals with Hageman factor deficiency have no hemorrhagic disorder, this case emphasizes the role factor XII may normally assume in clot dissolution.

Blood Coagulation Disorders

A comparison of the active stiffness of fetal and adult cardiac muscle.

This report described the in vitro analysis of the series elasticity of ventricular myocardium isolated from five fetal lambs and six adult sheep. Active compliance measurements were obtained by quick releases utilizing a closed loop servosystem and electromagnetic positioning device to control cardiac muscle length or tension. Right ventricular moderator bands were obtained from five fetuses (average 139 days of gestation, term=147 days), and compared with two adult moderator bands and four adult right ventricular trabeculae carneae. After correction for equipment coupling the experimental load extension data were fit to an exponential expression by a least squares technique: strain=1/b ln (1 + stress/a). When fetal and adult data were compared, no age-related differences in the constants were observed (a=0.185 +/- 0.062 SE (fetal) and 0.159 +/- 0.03 g/mm2 (adult); b=40.4 +/- 5.2 (fetal) and 43.1 +/- 5.2 (adult); and ab=7.39 +/-2.34 (fetal) and 5.27 +/- .99 (adult). However, significant variation existed in the histologically determined amount of contractile tissue present in muscle samples from both fetus (57-85%, average=74.0 +/- 4.9) and adult (64-94%, average=82.3 +/- 5.3). Wihtout regard to age, a signficant correlation was found between the b stiffness constant and the amount of contractile mass present in cardiac muscle. Thus, it is concluded that there is no age-related difference in the stiffness of fetal and adult ventricular muscle. However, there is a significant relationship between active compliance and true muscle mass.

Age Factors

Passovoy factor.

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Blood Coagulation Factors

Passovoy factor: A hitherto unrecognised factor necessary for haemostasis.

A moderate bleeding diathesis transmitted as an autosomal dominant was found in five members of four generations of the same family. The affected patients had prolonged partial thromboplastin-times and normal levels of all the known clotting-factors. The haemorrhagic diathesis was attributed to a deficiency of a hitherto unrecognised coagulation factor--i.e., the Passovoy facto.

Adult

Theoretical analysis of ligand-binder complex formation: partial equilibrium and incubation time.

This report presents a theoretical model of the rate at which complex formation approaches equilibrium in competitive binding systems while ligand concentration varies. Three commonly encountered systems are examined in which binder concentrations (q) are fixed at 0.5/K, 3/K and 50/K, respectively. Our analysis of the incubation time for any particular fraction of reaction completeness shows that longest incubation times occur with the lowest ligand concentrations when q = 0.5/K. However, in systems where q = 3/K and q = 50/K, the longest incubation times correspond not to lowest ligand concentrations but to those approximating the concentration of binder. It is concluded that empirical determination of minimal incubation times for these latter two assay systems should be performed with ligand and binder in approximately equal concentrations.

Kinetics