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Biomedical subjects

B D Reid

Publications and source records attributed to B D Reid.

At least 19 recordsLinked to original sources

The Sterways process: a new approach to inactivating viruses using gamma radiation.

The Sterways process (Process) provides a means of terminally sterilizing and virally inactivating blood products. The Process uses gamma radiation in a controlled manner to achieve maximum viral kill with minimum product loss. This goal is achieved by controlling the dose rate for the particular product and formulation in question. Because the Process uses gamma radiation it not only inactivates known viruses but also emerging or mutilating viruses.

Animals↗

Modulation and detection of IDDM by membrane associated antigens from the islet beta cell line NIT-1.

We have utilized the NOD islet beta-cell line NIT-1 to monitor beta-cell specific autoantibodies and to investigate the modulation of IDDM in NOD mice by NIT-1 membrane associated antigens. The sera from diabetic but not from pre-diabetic or protected NOD mice strongly stained NIT-1 cells in FACS analysis. The cell surface antigens on NIT-1 cells were trypsin-sensitive. NIT-1 cells could not be stained by anti-mouse GAD67 antibody; however, we could demonstrate the presence of GAD65 and GAD67 mRNA by RT-PCR. Longitudinal analysis of anti-NIT-1 antibodies showed that these antibodies were present in the neonates but disappeared after weaning. Sonicated NIT-1 cell membrane preparations protected NOD mice from diabetes when injected intravenously in 5 week old mice. The protection was associated with reduced cytotoxic activity and elevated Th2-like responses as indicated by IgG1 antibodies against the NIT-1 cells. Subcutaneous injection of sonicated NIT-1 membranes or the injection of control red blood cell membranes failed to induce protection. We conclude that NIT-1 cell membranes do not express GAD but contain other antigens that are important in the development and prevention of IDDM. These antigens could be useful for the diagnosis of diabetes by monitoring autoantibody levels and for the modulation of IDDM by immunotherapy.

Animals↗

Calcium and the Fc receptor on human platelets.

We have described the calcium dependence of the IgG Fc receptor (Fc-R) on human platelets by analyzing the direct binding of radiolabelled Fc fragments, monomers and dimers of IgG. Specific binding to platelets was undetectable at 37 degrees C in a calcium-free preparation but readily detected when calcium was restored. Scatchard analysis of the binding data for the calcium-restored platelets permitted calculation of the available Fc-R and the Ka of binding for the different IgG ligands. The mean Ka of binding for 12 normal subjects varied from 10(7) to 10(8) L/M, with an equal receptor number measured by Fc fragments and dimers of IgG, but a lesser amount for monomeric IgG. There was no apparent difference in Fc-R number for platelets from 6 normal male versus 6 normal female subjects. At 4 degrees C binding was detectable for dimers and polymers of IgG in a calcium-free preparation and this was markedly increased with recalcification. Thus, our data are consistent with an Fc receptor population on human platelets whose avidity for binding is significantly enhanced in a calcium-restored medium.

Blood Platelets↗

The effects of a thromboxane synthase inhibitor, a prostacyclin analog and PGE1 on the nephritis of the NZB/W F1 mouse.

One hundred NZB/W F1 female mice were studied to compare the effects of a thromboxane synthase inhibitor (TSI), a stable prostacyclin analog (iloprost) and prostaglandin E1 (PGE1) in the evolution of the nephritis. At 10 weeks of age mice were randomly assigned to cohorts of 20 to receive either no treatment, vehicle control, PGE1, iloprost or TSI. Proteinuria, mortality, systemic blood pressure, renal immune complex deposition, urinary TX B2 and 6 keto PGF1 alpha levels were measured. Mice receiving PGE1 and iloprost had a significant delay in the onset of proteinuria and reduction in mortality at 40 weeks. The TSI treatment had no apparent effect on proteinuria or mortality. The amelioration of the nephritis was not associated with an alteration in immune complex deposition in survivors at 40 weeks. Although PGE1 and iloprost lessened the age related increase in urinary TX B2, increased the urinary 6 keto PGF1 alpha levels and the ratio of 6 keto PGF1 alpha to TX B2; so did the TSI. The PGE1 treated mice did experience a marked and persistent reduction in blood pressure but this was not observed in the iloprost- or the TSI-treated mice. All drugs tested reduced the age-related increase in thromboxane B2 but only the PGE1 and iloprost had a significant effect on the evolution of the nephritis.

6-Ketoprostaglandin F1 alpha↗

Human platelet-immune complex interaction in plasma.

The plasmas of four patients with SLE were found to contain two anti-DNA antibody populations of widely varying affinity. The addition of double-stranded DNA to the anti-DNA plasmas resulted in formation of precipitating (insoluble) and soluble immune complexes. Human platelets suspended at physiologic concentrations in the anti-DNA plasmas during the immune complex formation underwent aggregation and release that correlated positively with precipitating (insoluble) immune complex formation but not with soluble complex formation. Preformed insoluble immune complexes induced platelet aggregation and release in a significant linear fashion, and release was inhibited by increasing concentrations of soluble immune complexes or Fc-fragments. The release reaction was completely inhibited by blocking the Fc-pieces of the preformed insoluble DNA-anti-DNA immune complexes. Soluble complexes of DNA-anti-DNA and A-anti-A at equimolar IgG concentrations produced similar degrees of inhibition, which were much greater than equimolar concentrations of Fc-fragments. The ability of increasing concentrations of soluble immune complex formed at fixed antibody concentration to cause greater inhibition of platelet release suggests that occupancy of the antigen binding sites of the antibody increases its ability to block the platelet Fc-receptor. The inhibition is similar for soluble complexes of varying antigen molecular size. This is compatible with the concept that a conformational change in the antibody occurs after antigen binding and results in an increase in binding strength at the platelet Fc-receptor site. We conclude that insoluble DNA-anti-DNA immune complexes induce aggregation and release of human platelets at physiologic concentrations in plasma via the platelet Fc-receptor.

Antibodies, Antinuclear↗

Failure to demonstrate renal uptake of labelled platelets in chronic glomerulonephritis.

1. Renal localization of autologous 111In-labelled platelets was studied in patients with chronic glomerulonephritis. External imaging was performed with a gamma-camera fitted with a medium energy collimator and the images were collected by a computer. 2. Images of 111In-labelled platelet distribution showed that there was a marked contribution to the radioactivity within each renal silhouette from adjacent spleen or liver. It was not possible to demonstrate renal accumulation of 111In-labelled platelets. 3. The application of 111In-labelled platelets to the study of intrarenal platelet consumption in chronic glomerulonephritis is limited by the sensitivity of current techniques and the scatter from adjacent splenic and hepatic radioactivity.

Adult↗

Radiotracer assessment of gastric mucosal permeability after hypovolemic shock.

Acute lesions of the gastroduodenal mucosa may result from gastric mucosal ischemia with subsequent cellular dysfunction, capillary leakage and increased susceptibility to mucosal damage. A new technique for measuring the effect of hypovolemic shock and gastric mucosal permeability is presented. Piglets were injected intravenously with human serum albumin labelled with 100 micro Ci of iodine-131 (131I-HSA). Serial blood and gastric samples were obtained for gamma counting during the control, hypovolemic shock and resuscitative periods. Increased gastric acid secretion and clearance of labelled serum albumin occurred after resuscitation from hypovolemic shock. The authors believe that increased capillary permeability and defective gastric mucosal cell function due to ischemia contribute to these changes.

Animals↗

The role of heparin on platelet retention by acrylonitrile co-polymer dialysis membranes.

The role of heparin on platelet--foreign surface interactions was examined by platelet retention studies on acrylonitrile--dimethylaminoethyl methacrylate (AN-DMAEMA) dialysis membranes both with and without the bonding of heparin onto their surfaces. Heparin bonding significantly reduced platelet retention. Heparin in solution (4 units/ml.) increased platelet retention when the surface of the membranes was modified by ethylene oxide but had no significant effect on the platelet-retaining properties of unmodified membranes. Studies using heparin 99mTc demonstrated that unmodified membranes took up heparin from solution whereas ethylene oxide-modified membranes had little such affinity. The heparin bonding process greatly increased the heparin uptake achieved by simple soaking in heparin solution, and the leaching rate was less than 1% at 70 hours. The results indicate that heparin has two antagonistic effects in this platelet-foreign surface interaction: it acts directly on platelets to increase adhesiveness while acting on the foreign surface to reduce platelet retention.

Acrylates↗

Lung and leg scanning with 99mTc-labelled albumin macroaggregates.

The routine injection of (99m)Tc-macroaggregated albumin into dorsal foot veins for lung scanning allows en passant assessment to be made regarding the presence of deep venous phlebitis. The radiopharmaceutical adhered to fibrin deposits in veins of calves and thighs in 103 of 386 examinations. In the 103 patients with a presumptive diagnosis of thrombophlebitis, microembolization from labelled thrombi, producing "hot spots" in the lungs, occurred in 25 cases. It is inferred that pulmonary microembolization is a very common event in patients with phlebitis.

Albumins↗

Partial purification of mitochondrial RNA polymerase from rat liver.

Mitochondrial RNA polymerase activity from rat liver has previously been demonstrated in intact organelles. This activity has now been solubilized, partially purified, and shown to be a true polymerase, free of nuclease. The enzyme is derived from mitochondria and is not from contaminating bacteria or nuclear components. The enzyme is distinguished from its nuclear counterparts by its behavior on ammonium sulfate fractionation and lack of inhibition by alpha-amanitin. Rifamycin inhibits the crude enzyme, but only inconsistently inhibits the more purified preparation.

Ammonium Sulfate↗