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Biomedical subjects

R G Mason

Publications and source records attributed to R G Mason.

At least 91 records · Page 5Linked to original sources

Experimental interactions of components of hemodialysis units with human blood.

An in vitro model test system for estimation of the blood compatibility of hemodialysis membranes and tubing is described. The model test system consists of a modified hemodialysis unit and blood pump through which fresh citrated human blood is circulated. The effects of the use of different pump and tubing types upon hematologic and blood coagulation parameters are described. Preexposure of test surfaces to albumin appeared to enhance blood compatibility characteristics of the model test system, whereas preexposure to a high density lipoprotein preparation or a proteinpolysaccharide preparation was without appreciable benefit. Use of blood from subjects receiving aspirin resulted in enhanced blood compatibility in the test system as did use of heparin. Use of Warfarin or dextran did not appear to enhance blood compatibility of test surfaces under the conditions of this test system. Dialysis membranes and tubing which formed parts of the test system were examined by scanning and transmission electron microscopy in control tests and in tests for effects of proteins and antithrombotic agents.

Albumins↗

Regulation of hemoglobin beta-chain synthesis in bone marrow erythroid cells by alpha chains.

Synthesis of alpha and beta chains of hemoglobin was studied in vitro in intact reticulocytes and bone marrow cells. The cells were from rabbits having a variant form of hemoglobin in which L-isoleucine is in the alpha but not in the beta chains. This characteristic permitted a selective inhibition of alpha-chain synthesis to be produced by addition to the incubation medium of L-O-methylthreonine, an inhibitor of protein synthesis that is a specific antagonist of L-isoleucine. In studies with reticulocytes, 25 mM L-O-methylthreonine produced a 60-70% inhibition of alpha-chain synthesis, but beta-chain synthesis was unaffected even after incubation times for 4 hr. Because reticulocytes contain a pool of uncombined alpha chains which might have obscured the demonstration of an alpha chain-dependent mechanism for beta-chain synthesis, subsequent studies were done with bone marrow cells. The latter had little or no detectable alpha-chain pool. A substantial inhibition of alpha-chain synthesis by the bone marrow cells was produced by the isoleucine antagonist but was also accompanied by a significantly decreased rate of beta-chain synthesis. These findings suggest that the coordinated synthesis of the complementary alpha- and beta-globin chains of hemoglobin may reflect in part a modifying effect of alpha-chain synthesis on the synthesis of beta chains.

Arginine↗

Hemoglobin Abraham Lincoln, beta32 (B14) leucine leads to proline. An unstable variant producing severe hemolytic disease.

An unstable hemoglobin variant was identified in a Negro woman with hemolytic anemia since infancy. A splenectomy had been performed when the patient was a child. The anemia was accompanied by erythrocyte inclusion bodies and excretion of darkly pigmented urine. Neither parent of the proposita demonstrated any hematologic abnormality, and it appeared that this hemoglobin variant arose as a new mutation. Erythrocyte survival in the patient was greatly reduced: the erythrocyte t(1/2) using radiochromium as a tag was 2.4 days, and a reticulocyte survival study performed after labeling the cells with L-[(14)C]leucine indicated a t(1/2) of 7.2 days. When stroma-free hemolysates were heated at 50 degrees C, 16-20% of the hemoglobin precipitated. The thermolability was prevented by the addition of hemin, carbon monoxide, or dithionite, suggesting an abnormality of heme binding. An increased rate of methemoglobin formation was also observed after incubation of erythrocytes at 37 degrees C. The abnormal hemoglobin could not be separated from hemoglobin A by electrophoresis or chromatography, but it was possible to isolate the variant beta-chain by precipitation with p-hydroxymercuribenzoate. Purification of the beta-chain by column chromatography followed by peptide mapping and amino acid analysis demonstrated a substitution of proline for beta32 leucine. It appears likely that a major effect of this substitution is a disruption of the normal orientation of the adjacent leucine residue at beta31 to impair heme stabilization.

Adult↗

Effects of certain purified plasma proteins on the compatibility of glass with blood.

The effects of certain purified plasma proteins on the coagulation-activation and platelet-adhesion properties of glass surfaces have been investigated. Albumin, transferrin, gammaG globulin, gammaM globulin and fibrinogen were obtained in highly purified form; ceruloplasmin was a more crude preparation. Each of these proteins was found to adhere to glass surfaces and influence reactions of these surfaces with blood. gammaG globulin or albumin adsorbed to glass markedly inhibited activation of the intrinsic coagulation system, while the other proteins tested were much less effective in this respect. Fibrinogen, of all the proteins tested, greatly enhanced the adhesion of platelets to glass. Albumin, ceruloplasmin, transferrin, gammaG globulin and gammaM globulin each decreased the adhesion of platelets to glass by approximately 50%. Ultrastructural studies of the interface area where blood reacted with the layer of protein adsorbed to glass demonstrated the deposition of a moderately thick irregular protein layer upon the surface, with adhesion of cellular elements to this unilaminar adsorbed layer. Ultrastructural studies also demonstrated that platelets which adhere to protein-coated surfaces formed pseudopods and spread upon such surfaces.

Afibrinogenemia↗

Freeze-etch observations on the plasma membrane and other structures of normal and abnormal platelets.

Human platelets in plasma were subjected to freeze fracture followed by etching. The outer surface of the platelet plasma membrane was exposed by etching but not by fracturing and was clearly identified by use of latex particles as markers. Surface-associated particles, apparently embedded in the plasma membrane, were found to measure from 83 to 332 A in diameter. Similar particles were associated with membranes lining the surface-connected canalicular system and with limiting membranes of storage granules. Fortuitous fractures exposed two inner faces of the plasma membrane, one of which contained greater numbers of surface-associated particles than did the outer surface of the plasma membrane. The second inner face of the plasma membrane contained numerous fibrillar structures measuring up to 770 A in length. Platelets from a congenitally afibrinogenemic patient appeared normal when examined by freeze-etch technics. Normal platelets exposed to a potent antiaggregating agent (REM 10,393) were found to have lost most of the particles associated with the outer surface of the plasma membrane and to have developed numerous defects in this membrane. A possible role for surface associated particles in platelet aggregation was further suggested by the finding that the nonaggregable platelets of two congenitally thrombasthenic sisters were nearly devoid of these structures.

Afibrinogenemia↗