NMR of paramagnetic proteins.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C Macdonald.
Explore the source record for details and available documents.
Clearance of Listeria monocytogenes in experimental models of infection has underscored the importance of interferon-gamma (IFN-gamma) in host resistance to intracellular pathogens. Because L. monocytogenes infections are more severe in newborns than adults, we compared IFN-gamma accumulation in the supernatants of mononuclear cells infected in vitro from newborns with those from adults. Supernatants were assayed for IFN-gamma using an enzyme-linked immunosorbent assay. Uninfected newborn and adult mononuclear cells had less than 50 pg/ml of IFN-gamma at all times tested. IFN-gamma levels in supernatants from infected adult mononuclear cells at 24 h of culture (1.15 x 10(3) +/- 0.92 pg/ml) were greater than supernatants from infected newborn mononuclear cells (0.19 x 10(3) +/- 0.33 pg/ml). IFN-gamma concentrations in newborn cell cultures plateaued on day 3 of culture (1.6 x 10(3) +/- 1.1 pg/ml) and were not significantly less than concentrations from adult cells. However, adult cell IFN-gamma was further increased by day 5 (18.7 x 10(3) +/- 21.8 pg/ml). Because IFN-gamma plays a critical role in the host defense against L. monocytogenes, this delay in the release of IFN-gamma may be a factor in the increased susceptibility and severity of infection in the neonate.
The production of tumor necrosis factor alpha (TNF alpha) activity by peripheral blood mononuclear cells (PBMC) was determined in uremic patients on chronic hemodialysis (HD; n = 27), continuous ambulatory peritoneal dialysis (CAPD; n = 19), and in patients with chronic renal failure who were not yet on dialysis (CRF-ND; n = 18). In the HD group blood was taken immediately prior to and immediately following an HD session utilizing a cellulose acetate dialyzer. Post-HD PBMC spontaneously (i.e. in serum free media) produced significantly more TNF alpha activity than the PBMC of all other patient groups as well as those of the normal controls (n = 41) (p < 0.003). Post-HD PBMC produced significantly more TNF alpha activity than pre-HD PBMC both spontaneously and in the presence of nonuremic sera (p < 0.003). PBMC prior to HD also produced significantly more. TNF alpha activity than CAPD PBMC and normal PBMC in the presence of autologous heat inactivated sera (p < 0.03). Under some culture conditions (i.e. in the presence of nonuremic sera) normal PBMC produced significantly (p < 0.003) more TNF alpha activity than CAPD PBMC. Finally, a positive correlation was found between PBMC TNF alpha activity and age for HD patients (r = 0.7, p < 0.004) but not for CAPD or CRF-ND patients. These findings suggest that PBMC of HD but not CAPD or CRF-ND patients are chronically stimulated to produce TNF alpha activity.(ABSTRACT TRUNCATED AT 250 WORDS)
The production of TNF alpha by peripheral blood mononuclear cells (PBMC) was determined in 18 hemodialysis (HD) patients. Blood was taken from each patient before and after an HD treatment. Both pre- and post-HD PBMC produced significantly more TNF alpha than controls (TNF alpha units/ml; mean +/- SEM; controls 3.1 +/- 0.7; pre-HD 9.7 +/- 3.9; post-HD 19.8 +/- 7.7, p < 0.05). In addition, post-HD PBMC produced significantly more TNF alpha than pre-HD PBMC suggesting that the HD procedure itself may activate cytokine production. This was true when PBMC were cultured in serum free medium as well as on culture with non-HD sera (human AB) and autologous sera. A positive correlation was also found between the production of TNF alpha and age in HD patients (r = 0.58; p < 0.01). Finally, normal PBMC cultured in post-HD sera produced significantly less TNF alpha than when cultured in the same sera pre-HD (p < 0.02). These findings suggest that PBMC of HD patients are chronically stimulated to produce TNF alpha which may contribute to some of the short-term and long-term complications of HD.
Two murine peritoneal macrophage cell lines have been isolated by transforming primary cells with simian virus 40 (SV40) origin-deleted DNA. These lines have been maintained in continuous culture for over 8 months and have been shown to express macrophage-specific properties throughout this time. The cell lines are F4/80 positive; express Fc receptors; will phagocytose immunoglobulin-coated red cells and latex beads; stain with neutral red; and have non-specific esterase and plasminogen activator activities. Lysozyme, collagenase, prostaglandin E2, acid phosphatase and 5'-nucleotidase activities have also been detected and quantified.
We examine the average economic status of baby boom cohorts as they approach retirement chiefly using data on their life cycle income experience to date. Contrary to popular impression, baby boomers are likely to enter old age in an even better economic position than pre-boom cohorts. Economic and demographic adjustments that they made, such as deferred marriages, reduced childbearing, and increased labor force participation of wives, have compensated for their relatively low wage rates. Potential downside effects of reduced childbearing regarding Social Security and health care prospects are discussed.
A highly sensitive and quantitative assay for measuring protein in solution based on the capacity of protein to bind silver is described. In this procedure, protein samples are first treated with glutaraldehyde and then exposed to ammoniacal silver. After 10 min, the reaction is terminated by the addition of sodium thiosulfate and the optical density measured at 420 nm. The useful range of the assay for the majority of standard proteins tested lies between 15 and 2000 ng. This represents a 100-fold increase in sensitivity over the Coomassie brilliant blue dye-binding procedure. There is little or no interference from carbohydrates, nonionic detergents, or ethanol, and pretreatment of protein samples with Bio-Gel P-2 to remove salts, thiol agents, EDTA, and sodium dodecyl sulfate makes this procedure compatible with most commonly used buffers. The cost in terms of silver utilization is nominal with a typical assay involving 10 samples tested in triplicate amounting to less than $0.02 U. S.
Antihemophilic factor (AHF) essentially free of von Willebrand factor (vWF) was used to determine whether vWF affected the coagulant activity of AHF in a kaolin-activated system using platelet-rich plasma. The AHF was prepared by sequential chromatography on solid-phase polyelectrolyte (PE E-5), and on Sepharose CL-4B in the presence of a high concentration of CaCl2. Residual traces of vWF antigen were removed by affinity chromatography with immobilized anti-vWF IgG. The essentially vWF-free AHF corrected the clotting defect of plasma from three patients with severe von Willebrand's disease (vWD) as measured by the kaolin-activated clotting time in the presence of normal or vWD platelets ( Hardisty - Hutton test). Addition of hemophilic plasma as a source of vWF did not cause additional improvement, nor did a potent antibody to vWF raised in rabbits inhibit the ability of AHF to shorten the clotting time of vWD plasma. Thus we found no evidence that vWF is necessary for AHF to function in the coagulation of recalcified kaolin-activated vWF-deficient platelet-rich plasma.
Five experiments which attempted to evaluate the relationship between orientation and curvature selectivity in human vision are described. In the first two experiments, threshold elevation for curved gratings was measured after exposure to similar gratings, with the use of either an adaptation (experiment 1) or a masking (experiment 2) paradigm. In both experiments threshold elevation occurred which was selective for both the degree and the direction of curvature of the adapting pattern. Experiment 3 compared the effects of adapting to tilted rectilinear or vertical curved gratings upon threshold for a vertical rectilinear grating. Threshold elevation declined systematically as the adapting gratings were either tilted or made more curved. Experiment 4 measured curvature selectivity as a function of the orientation of a curved adapting grating. Threshold elevation declined as the adapting grating was tilted more, but curvature selectivity remained. Experiment 5 measured the orientation tuning for curved gratings directly. Threshold elevation declined to 50% of its maximum value at an adpating orientation of about 28 degrees. This was constant for all values of curvature used. The resulsts are discussed with reference to the question of whether the human visual system contains 'curvature detectors' or linear-contour detectors which respond to the tangents of curves.
Lymphocytes from sixteen patients with extrinsic bronchial asthma and sixteen normals were investigated for their in vitro reactivity to stimulation with phytohaemagglutinin (PHA) and concanavalin A (Con A). No significant differences in maximum lymphocyte responses to PHA or Con A, either in the presence of foetal calf serum or autologous plasma, were found. The significance of these results in relation to T suppressor cell control of IgE formation is discussed.
This report sets forth an example of a new mode of management of severe craniosynostosis in the neonate: subtotal calvariectomy. An infant with synostosis of sagittal, coronal, and lambdoidal sutures who had signs of increased intracranial pressure with impending neurologic complications was operated on at 13 days of age. Wide excision of the bony calvarium from the underlying dura was accomplished from the supraorbital ridge to near the foramen magnum; the entire area of the coronal sutures was included. Regeneration of the calvarium occurred over two to 12 weeks and was accompanied by the presence of "sutures" in a usual location. These procedures have allowed for normal brain growth without reoperation up to the current age of two years. Neurologic and intellectual performance has been satisfactory, and cosmetic results appear to be preferable to those obtained by more limited surgery. The observations suggest that this approach may permit better craniofacila growth by minimizing secondary deformities in growth of the cranial base.
Explore the source record for details and available documents.
The value of adding a sedative to commonly used analgesic agents to promote further the relief of pain was studied by a double-blind procedure in 90 post-surgical patients during 188 pain episodes. In moderate pain episodes, no statistically significant difference between the analgesic-sedative combination (Fiorinal-C(1/4)) and the analgesic (APC-C) was observed, although both compounds were superior to placebo (p <0.001). In severe pain episodes, the analgesic-sedative combination was superior to the analgesic alone; the analgesic, in turn, was superior to placebo (p <0.001).It is concluded that analgesia is more effective if associated apprehension is relieved by sedation.
Explore the source record for details and available documents.