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Biomedical subjects

M E Conrad

Publications and source records attributed to M E Conrad.

At least 109 records · Page 6Linked to original sources
PubMed1977

Tissue factor generation by human mononuclear cells: effects of endotoxin and dissociation of tissue factor generation from mitogenic response.

The effects of the presence of endotoxin in a mononuclear cell culture system have been assessed. Endotoxin was shown to be mitogenic for human peripheral blood lymphocytes and capable of stimulating the generation of tissue factor. Concentrations of endotoxin, found to contaminate many commercial mitogens and antigens, activated mononuclear cells in a time-dependent manner. Generation of tissue factor was detected in cultures harvested from 2 to 72 hours following stimulation with endotoxin. Dose-response curves relating concentrations of endotoxin to mononuclear cell stimulation were determined; as little as 0.001 microng/ml. of E. coli endotoxin was capable of stimulating the generation of tissue factor in the cell cultures. The mitogenic effect of endotoxin was modest, however, and appeared to be unrelated to the ability of endotoxin to active tissue factor. Inhibition of DNA synthesis in the cell cultures by cytosine arabinoside or nonlethal irradiation failed to impair the generation of tissue factor. Endotoxin contamination of various reagents used in cell culture was evaluated with the Limulus assay, which detected as little as 1 X 10(-4) microng/ml. of endotoxin. Endotoxin was detected in preparations of phytohemagglutinin, purified protein derivative of the tubercle bacillus, mumps vaccine, tetanus toxoid, concanavalin A, and pokeweed mitogen. Because of the broad implications of contamination by endotoxin of various reagents, we assessed the specificity of the Limulus assay for the detection of endotoxin in the lectin, concanavalin A, and determined that the reaction was specific for endotoxin. Contamination by endotoxin of mononuclear cell culture systems should be considered as a possible factor in the production of various biological effects attributed to some commonly used mitogens and antigens.

Cytarabine↗
PubMed1977

Development of chronic liver disease after acute non-A, non-B post-transfusion hepatitis. Role of gamma-globulin prophylaxis in its prevention.

Progression of acute type B hepatitis to chronic liver disease and cirrhosis is well recognized, whereas no progression of acute type A hepatitis has as yet been documented. The natural history of acute non-A, non-B hepatitis has not been previously characterized. Ten cases of chronic liver disease were identified in 44 cases of acute non-A, non-B post-transfusion hepatitis. Age, sex, severity of acute illness, and prevalence of preoperative antibodies to known hepatitis-producing agents did not differ between the group whose hepatitis progressed to chronicity and the group whose hepatitis resolved. Less progression of acute hepatitis to chronic liver disease was seen in those patients receiving immune serum globulin preoperatively than in those receiving an albumin placebo (P = 0.009). Only 3 patients had clinical symptoms of hepatitis at the time of liver biopsy, and elevations of liver enzymes and gamma-globulin were mild. However, liver biopsy specimens in 8 of 10 patients showed chronic active hepatitis and an additional biopsy specimen showed cirrhosis. Acute non-A, non-B post-transfusion hepatitis often progresses to chronic active hepatitis. Preoperative gamma-globulin prophylaxis significantly reduces this progression. Identification and characterization of this viral agent(s) will further aid in the prevention of this undesirable complication of blood transfusion.

Acute Disease↗
PubMed1976

Efficacy of prophylactic gamma-globulin in preventing non-A, non-B post-transfusion hepatitis.

Of 279 cardiac-surgery patients receiving a mean of twelve transfusions, 47 had significantly increased transaminase concentrations 14 to 180 days postoperatively and 10 were icteric. Preoperatively, each patient randomly received high-titre HbsAb gamma-globulin, normal gamma-globulin, or placebo and was followed at intervals for 9 months. Only 3 patients had serological evidence of hepatitis-B infection. 3 additional patients had serological evidence of cytomegalovirus infection, while none had evidence of hepatitis-A or Epstein-Barr infection. Less icteric hepatitis occurred in patients receiving the gamma-globulin preparations (P = 0-003), and the overall frequency of hepatitis was significantly reduced when compared with recipients of placebo. The protective effects of the two gamma-globulin preparations were not significantly different. Most post-transfusion hepatitis tody is neither viral hepatitis type B nor type A, and its severity and transmission are reduced by pre-transfusion gamma-globulin.

Adult↗
PubMed1976

Procoagulant and platelet aggregating properties of antilymphocyte sera.

Ten anti-human lymphocyte sera in clinical use at six transplant centers and five anti-nonhuman lymphocyte sera were studied for their procoagulant and platelet-aggregating properties. This investigation was initiated following the observation of a clinical episode of renal artery thrombosis, associated with the use of one of the sera in a patient who had received a cadaveric renal transplant. The procoagulant from this serum shortened the clotting times of individual samples deficient, respectively, in factors XII, XI IX, X VIII, and VII. Esterolytic activity, demonstrated on the substrate benzoylarginine ethyl ester, was completely inhibited by phenylmethylsulfonyl fluoride, but coagulant activity was variably affected. The platelet-aggregating activity (PAA) has been identified as a complement-fixing gamma G antibody that was absorbed from the antilymphocyte serum (ALS) with human spleen lymphocytes. Five of the ten anti-human lymphocyte sera showed varying procoagulant activity (PCA), and six sera demonstrated PAA. Three sera contained both activities. The presence of both PCA and PAA in the same preparation may predispose patients to thrombotic events, particularly if administered intravenously. Sera should be screened for PCA and PAA prior to clinical use, and sera with these properties should be used with caution.

Animals↗
PubMed1975

Clinical trials of hepatitis B immune globulin. Development of policies and materials for the 1972-1975 studies sponsored by the National Heart and Lung Institute.

Plasma from persons with high titers of hepatitis B antibody (anti-HBs) was used to manufacture one lot of hepatitis B "immune" globulin sufficient for four interlocking clinical trials of prevention or modification of hepatitis B infections. The trials were carried out in renal dialysis units, in medical personnel with accidental exposures to hepatitis B, in transfused patients, and in patients with fulminant hepatitis. A single policy board developed protocols that allowed comparisons among the four studies while respecting the unique requirements of each.

Antibodies↗
PubMed1975

Endogenous production of carbon monoxide as measured simultaneously in blood and gas phase.

Endogenous carbon monoxide (CO) production rates and total body haemoglobin content were determined simultaneously in blood and gas phase in 15 individuals. At 24% oxygen (O2) concentration in the closed rebreathing system, a correlation was obtained which revealed that a 1 mumole rise in CO in the gas phase of the system was the result of 48.94 +/- 5.3 (SE) mumoles of CO rise in the body. Three individuals had heat-damaged red cells reinjected intravenously to determine if the recovery rate of the subsequently produced CO was proportionate in both the gas phase and blood phase. Changes in blood CO concentration were not consistently detected by gas phase analysis. Prediction of CO production rates utilizing gas phase data alone did not reflect accurately CO production rates determined from blood carboxyhaemoglobin rises.

Carbon Monoxide↗
PubMed1975

The abnormal surface characteristics of the red blood cell membrane in congenital dyserythropoietic anaemia type II (HEMPAS).

The red blood cell membranes of patients with congenital dyserythropoietic anaemia Type II (CDA-II) were found to be abnormal. They had altered antigenic characteristics, decreased electrophoretic mobility, decreased sialic acid content, and abnormal filtration through polycarbonate filters. Proteins extracted from the CDA-II erythrocytes showed a different banding pattern on polyacrylamide gels compared to normal erythrocytes. Erythrocytes from clinically unaffected siblings and parents showed similar but less striking abnormalities of antigenic surface characteristics and banding patterns on polyacrylamide gels with nearly normal surface charge, sialic acid content, and filtration properties. These studies suggest a correlation between the degree of membrane abnormality and the clinical state of the CDA-II family member, demonstrate the erythrocyte in the heterozygote state is not normal, and support the concept of CDA-II as an autosomal recessive disease.

Agglutination Tests↗
PubMed1975

Detection of platelet isoantibodies by (3H)serotonin platelet release and its clinical application to the problem of platelet matching.

The detection of platelet isoantibodies by the release of (3H)serotonin from platelets has been evaluated. The conditions for optimal release of (3H)serotonin with platelet isoantibodies using a microtechnique have been defined. A group of cardiac surgery patients were followed pre- and post-transfusions, with 48percent developing a positive serotonin release assay. Of these patients, 16percent also had a platelet complement-fixing and/or lymphocytotoxic isoantibody. There was variation in the degree of correlation between (3H)serotonin release and lymphocytotoxicity using individual National Institutes of Health typing serum. The matching obtained between family members by both techniques showed a close correlation when each technique was evaluated separately using the same NIH typing serum. The detection of iso-antibodies in patients with hematological malignancies correlated with the unresponsiveness to unmatched platelet transfusions in 15 out of 17 cases. The use of the patient's isoantibody to matched platelets of family members by (3H)serotonin release correlated well with the clinical response to transfusion with these platelets. The data suggest that (a) platelet isoantibodies can be detected with increased frequency by (3H)serotonin release; (b) (3H)serotonin release is a specific reaction depending on the surface antigen of the platelet; and (c) the method can be used to match compatible family members for platelet transfusions.

Blood Donors↗
PubMed1975

Alteration of human erythrocyte membrane properties by complement fixation.

Erythrocyte survival studies of complement-coated radiolabeled erythrocytes have shown rapid removal of these cells from the peripheral blood with a return of these cells into the circulation within a few hours. We studied complement-coated human erythrocytes and measured surface charge and deformability, two parameters believed to be important in erythrocyte survival. Erythrocytes were coated with complement by two in vitro techniques: the addition of (a) low ionic strength sucrose, and (b) IgM cold agglutinins. Erythrocytes obtained from three patients with cold agglutinin disease were used as a source of in vivo complement-coated cells. No difference was found in surface charge as measured by electrophoretic mobility between erythrocytes from normal subjects and complement-coated erythrocytes from any of the three sources. When deformability was measured by filtration through 3-mum polycarbonate sieves, marked decreases in deformability were found in complement-coated erythrocytes. The filtration returned toward control levels by incubating the complement-coated erythrocytes in serum for 1 h and correlated with decreases in immune adherence. Using screen filtration pressure as a measure of deformability, a positive correlation between number of C3 molecules per erythrocyte and decreased deformability was found. C3b appeared responsible for the decreased deformability of the erythrocytes, since conversion of C3b to C3d resulted in a return of deformability toward normal. The data suggested that the sequestration of complement-coated human erythrocytes in the microvasculature can be explained in part by decreased deformability and changes in immune adherence.

Agglutinins↗
PubMed1975

Effect of oral contraceptives and pregnancy on erythrocyte deformability and surface charge.

Erythrocyte deformability and surface charge were studied in normal premenopausal women, oral contraceptive users, and pregnant women. The increased incidence of thrombosis in women taking oral contraceptives could not be explained by decreased erythrocyte deformability or surface charge. However, the decreased erythrocyte deformability of late pregnancy may relate to thrombosis during this period and to increased hemolysis in patients with certain hemoglobinopathies.

Adenosine Triphosphate↗
PubMed1975

Mithramycin in the treatment of systemic mastocytosis.

A patient had systemic mastocytosis of 16 years' duration, with urticaria pigmentosa, osteopetrosis with severe bone pain, mastocytosis of the bone marrow with myeloid metaplasia, gastrointestinal malabsorption, and Cushingold features associated with prolonged usage of corticosteroids. Treatment with a single dose of mithramycin resulted in an abrupt disappearance of the patient's generalized bone pain, but it had little effect on his histamine release-type symptomatology.

Adult↗