Biomedical subjects

F A Green

Publications and source records attributed to F A Green.

At least 55 records · Page 3Linked to original sources

PubMed1986

The last public execution in Glasgow: the case of Dr Edward Pritchard, M.D.

Dr Edward Pritchard, a Glasgow medical practitioner, was the last person to be executed in public in Glasgow. In a famous trial of the time, he was condemned to death for murdering his wife and his mother-in-law, and he was hanged on Glasgow Green in 1865. An account of Dr Pritchard's life, his trial and his death is given here, together with a reference to the medical examination which was carried out on Pritchard's remains when his grave was exhumed in 1910.

Forensic Medicine↗

PubMed1986

Patterns of in vitro aspirin hydrolysis rates in rheumatoid arthritis and systemic lupus erythematosus.

In previous in vitro studies of normal human blood and in vivo canine studies an intracellular erythrocyte (RBC) esterase was identified which controlled the rate of aspirin (ASA) hydrolysis and thus modulated the duration of intact ASA survival and availability for transacetylations required for some therapeutic effects. In whole blood from 30 patients with systemic lupus erythematosus (SLE), 10 normal subjects, and 40 patients with active seropositive rheumatoid arthritis (RA), there were negative correlations between the hematocrit level and the ASA half-life in vitro: r = -0.50, -0.83, and -0.61, respectively. When ASA hydrolysis rates were normalized to approximate whole blood esterase content (k/Hb [min-1 X g-1 X dl] X 10(-4) the mean rate was most rapid in patients with RA (24.2 +/- 2.8) and lowest in patients with SLE (18.6 +/- 3.1), especially in those with recently active disease. To differentiate intracellular and extracellular factors, ASA hydrolysis rates were measured in washed RBC suspensions from similar groups. The mean ASA hydrolysis rate (k/10(6) RBC X 10(-3) was significantly lower in SLE RBC (7.72 +/- 0.81). In RBC from patients with RA the average rate (8.50 +/- 0.85) lay between the SLE group and controls (9.08 +/- 1.04). Thus, an erythrocyte esterase defect in SLE patients resulted in reduced ASA hydrolyzing capacity. In blood from patients with RA a small reduction in esterase activity was compensated by extracellular factors increasing ASA accessibility to the esterase.

Arthritis, Rheumatoid↗

PubMed1985

The osmotic response of human erythrocytes and the membrane cytoskeleton.

The volumes of human erythrocytes suspended in solutions of varying concentrations of sodium chloride and sucrose were measured by a Coulter Channelyzer Model H4 with appropriate corrections. The cells showed greatly restricted volume changes at osmolarities between 200-700 mOsm. At osmolarities outside this limit, on the other hand, the cells showed nonrestricted volume changes following essentially the predictions of an ideal osmometer. This unexpected volume response was not spuriously due to changes in shape or to a changing orientation of the cells as they traversed the aperture. The restricted volume change observed was abolished when the cells had previously been treated with diamide or had been heated for 60 minutes at 50 degrees C, conditions that are known to disturb the spectrin-actin network. The possibility must be considered that the osmotic behavior of human erythrocytes may be nonideal and that this nonideal behavior is primarily due to mechanical restriction provided by the spectrin-actin network of the membrane cytoskeleton.

Cytoskeleton↗

PubMed1985

Binding characteristics of anti-Rh0(D) antibodies to Rh0(D)-positive and Du red cells.

The relation of human erythrocyte Rh0(D) to Du sites is an important unresolved question in the field of immunohematology. To compare the immunological reactivity of Rh0(D)-positive and Du erythrocytes, the binding characteristics of two anti-Rh0(D) antisera to human Rh0(D)-positive and Du ("low-grade") erythrocytes were studied. 14C-Protein A and direct antibody-labeled techniques were used to generate binding curves and to derive double-reciprocal plots. The results show that the number of antigen sites differ by a factor of 10 to 15 between the Rh0(D)-positive and Du red cells, but that the dissociation constants between anti-Rh0(D) and the Rh0(D) and Du antigens are indistinguishable when studied by the two labeling methods and two different anti-Rh0(D) antibodies. The extent of binding to 112 different Du samples showed a normal distribution and was independent of apparent phenotype. These data suggest immunologic identity of Rh0(D) and Du ("low-grade") sites and that the difference between the antigens of Rh0(D) and Du cells is quantitative only. The data are incompatible with the "missing mosaic" and gene interaction theories of mechanism.

Antigen-Antibody Reactions↗

PubMed1984

The relative roles of hydrolases of the erythrocyte and other tissues in controlling aspirin survival in vivo.

The rate of aspirin (acetylsalicylic acid, ASA) deacetylation to salicylate in vivo determines the availability of the intact molecule for therapeutically important transacetylation reactions. Experiments were carried out to assess the relative contribution of a previously isolated human erythrocyte ASA esterase to the overall hydrolysis rate in vivo, as opposed to similar enzymes in other tissues. In vitro, the rates of ASA hydrolysis were relatively slow in plasma from humans and dogs. The hydrolysis rates were significantly greater in whole blood in dogs, rabbits, and humans. In human and canine whole blood, the rate of hydrolysis correlated positively with hematocrit. In vivo studies with dogs showed that ASA decay rates conform to a 2-compartment model. After reduction of hematocrit by a mean of 49% in 4 dogs without previous splenectomy, the "availability" of ASA increased. In 4 dogs with previous splenectomy, this measurement was increased even more after comparable hematocrit reduction. In 2 dogs that underwent a sub-total hepatectomy, ASA availability increased by only 35% and 12.8%, respectively. These results suggest a significant role for the erythrocyte esterase in vivo in the dog and possibly in humans.

Animals↗

PubMed1984

The phospholipid requirement for Rho(D) antigen activity: mode of inactivation by phospholipases and of protection by anti-Rh0(D) antibody.

Previous studies have suggested a membrane phospholipid requirement for Rho(D) antigen activity. Isolated erythrocyte membranes incubated with phospholipase A2 from both bee venom and porcine pancreas undergo loss of Rh antigen activity. The mode of attenuation of this antigen activity as indicated by double-reciprocal binding plots suggests substantial loss of sites accompanied by an apparently increased association constant. In the presence of anti-Rho(D), but not anti-A, bound to group A Rho(D)-positive membranes prior to hydrolysis, there is marked protection: almost complete preservation of sites at the expense of a decreased association constant. This pattern of protection is not seen with phospholipase C, which cleaves the polar headgroup in contrast to the A2-enzymes, which hydrolyze the fatty acid in the 2-position. Analysis of the products of digestion shows a trend to protection of bulk phospholipids of all major classes in the presence of bound specific antibody. The hydrophobic fatty acid chain may be the site with which the bound anti-Rho(D) antibody is in closest proximity.

Animals↗

PubMed1984

The prevalence and possible prognostic importance of arthropathy in childhood diabetes.

Specifically defined arthropathy was studied in 95 children with insulin-dependent diabetes mellitus. Thirty-eight patients (40%) had limited joint mobility (p = less than 0.001 vs healthy controls). Children with the following extraarticular findings were more likely to have arthropathy: tight skin of the hands (p = less than 0.001), retinopathy (p = less than 0.05), and/or decreased deep tendon reflexes (p = less than 0.01). When the frequency of articular findings was analyzed as a function of disease duration, a nearly linear increase in the percentage of children having joint findings was evident: 0-3 years, 28%, 4-8 years, 41%: greater than 8 years, 67%. The percentage of patients positive for any microvascular complication during these intervals rose much less sharply: 4-11%, 4-15%, and 24-52%. Since the fraction of children without any joint abnormality constantly decreases, the finding of arthropathy has little value beyond knowledge of disease duration as a predictor of the development of microvascular complications.

Adolescent↗

PubMed1984

Cardiac tamponade in systemic juvenile rheumatoid arthritis requiring emergency pericardiectomy.

A 9-year-old boy with systemic onset juvenile rheumatoid arthritis (JRA) presented with fever and chest pain and rapidly developed pericarditis and cardiac tamponade. Despite corticosteroid treatment and pericardiocentesis, rapid deterioration necessitated the emergency placement of a pericardial window. This is the first reported instance of this type of emergency surgical intervention for JRA. Of 220 children with JRA followed for 12 years (7% systemic onset), 8 had evidence of acute pericarditis but no other had definite evidence of tamponade.

Arthritis, Juvenile↗

PubMed1983

Identification and partial purification of the major aspirin hydrolyzing enzyme in human blood.

In normal whole human blood in vitro, the source of the enzyme controlling the hydrolysis of aspirin (ASA) was found to be the erythrocyte (RBC). Experiments were carried out to determine whether this enzyme was membrane-bound or free in the lysate. The mean rates of ASA hydrolysis in comparable concentrations of intact RBC (1.61 +/- 0.20 mumole/liter/minute, n = 12 and 1.23 +/- 01.7 mumole/liter/minute, n = 5) were much faster than that measured in isolated RBC membranes (0.23 +/- 0.08 mumole/liter/minute, n = 6, P = less than 0.001). Detailed study showed that the RBC-related ASA esterase is located intracellularly and is not related to membrane acetylcholinesterase. The ASA esterase from crude lysate was purified 900-fold by means of DEAE Sephacel chromatography of active enzyme recovered from a 50% saturated ammonium sulfate fraction. Non-SDS polyacrylamide gel electrophoresis (pH 8.3 and 9.0) resulted in one major band and one or more small minor protein bands. When esterase activity was assayed in a non-stained gel, ASA depletion and salicylate production corresponded exactly to the major stained band. This band was eluted from another unstained gel, concentrated, and applied to an SDS gel. This yielded a single band with a molecular weight of approximately 95,000. The partially purified enzyme had a mean Km of 66.6 +/- 3.5 microM and a mean Vmax of 4.0 +/- 0.9 mumole/liter/minute/mg under the assay conditions. The results of inhibition studies suggested that this enzyme's activity is sulfhydryl group dependent, does not require divalent cations for activity, and is different from the RBC type D "nonspecific" esterases.

Carboxylic Ester Hydrolases↗

PubMed1983

The role of choline phospholipids in hypertonic cryohemolysis.

Hemolysis resulting from a warm-to-cold temperature shift in a hypertonic environment (hypertonic cryohemolysis) is studied with the use of phospholipases as membrane probes of the phospholipids of the outer leaflet of the bilayer. Bee venom phospholipase A2 which attacks only phosphatidylcholine (PC) in the intact erythrocyte results in inhibition of cryohemolysis produced by both hypertonic sodium chloride and sucrose. In both cases, about 25% of the loss of PC occurs before any such inhibition, suggesting the possibility of functionally separate domains of PC in the outer leaflet of the bilayer. Sphingomyelinase also attacks only sphingomyelin in the intact erythrocyte and results in inhibition of cryohemolysis due to hypertonic sodium chloride but not of that due to sucrose. In each case, inhibition of the enzymatic hydrolysis by EDTA abolished the effect on cryohemolysis. It is postulated that cryohemolysis is inhibited when phospholipid interaction with membrane (cytoskeletal) proteins are abolished, but present knowledge of membrane structure does not permit a detailed mechanism to be proposed.

Cold Temperature↗

PubMed1983

Molecular size of the Rh0(D) antigen of the human erythrocyte in situ by radiation inactivation.

Radiation inactivation was used to determine the molecular size of the RhO(D) antigen of isolated membranes and of the intact human erythrocyte. Isolated membranes were frozen and irradiated at -50 degrees C. After thawing, the bound 14C-anti-D was measured and the log residual Rh(D) antigen activity was plotted against the radiation dose. A mol. wt of 60,000 was calculated. Intact human erythrocytes frozen in the presence of cryoprotective reagents were also studied. Rh(D) antigen inactivation occurred as a single exponential function of radiation dose which also yielded a mol. wt of approx. 56,000 upon analysis by classical target theory.

Dose-Response Relationship, Radiation↗

PubMed1983

The mode of attenuation of erythrocyte membrane Rh0(D) antigen activity by 5,5'-dithiobis-(2-nitrobenzoic acid) and protection against loss of activity by bound anti-Rh0(D) antibody.

The Rh0(D) antigen activity of human erythrocyte membranes is lost on treatment with the aromatic disulfide, 5,5'-dithiobis-(2-nitrobenzoic acid), reacting by specific disulfide interchange with membrane thiols. The inactivation rate of the antigen was first order with respect to inhibitor concentration and a double reciprocal plot of the inactivation rate constants against the sulfhydryl reagent concentration was linear, giving an apparent dissociation constant of 1.25 mM and indicating that a binding step preceded covalent interaction. In a study of the binding characteristics of anti-Rh0(D) to the 2-nitro-5-thiobenzoate derivative of the membrane Rh0(D) antigen, the maximum number of binding sites fell with increasing sulfhydryl reagent concentration but the apparent association constant also diminished at the same rate. The inactivation of the Rh0(D) antigen was greatly retarded by the presence of bound anti-Rh0(D), a protective effect not seen with normal serum. Bound anti-Rh0(D) antibody protects against both the loss of sites and the change in affinity brought about by DTNB. It is concluded that a single critical thiol whose reactivity is altered by bound anti-Rh0(D) antibody is involved in the membrane Rh0(D) antigenic determinant site. These observations may permit extensive probing of the microenvironment of this essential cysteine residue.

Dithionitrobenzoic Acid↗

PubMed1983

A prospective analysis of the frequency, course, and possible prognostic significance of the joint manifestations of childhood leukemia.

During a 2-year prospective study of 28 leukemic children (24, acute lymphocytic leukemia [ALL]; 4, non-ALL) unselected for musculoskeletal symptoms, objective joint findings were present in 14 cases (p = 0.001 vs normal controls). These findings varied in severity, were most frequently present in the knee (12 of 14 children), and were found most frequently only at disease onset (7 of 14). The group with joint abnormalities had a higher frequency of functionally significant joint complaints prior to diagnosis of leukemia (p = less than 0.01) and radiographic abnormalities of periarticular bone of the knees and ankles (p = less than 0.10). Four of the 5 children with ALL who died had joint findings, a trend whose significance is uncertain because of unequal followup periods.

Child↗

PubMed1982

Free versus bound salicylate concentration in adults and children with chronic inflammatory joint disease: serum albumin and other potential factors affecting the levels.

Salicylate (SA) binding to albumin in purified human serum albumin (HSA) solutions was found to be predictably dependent on the concentrations of albumin and total SA. The influence of the presence of other ligands on SA binding in HSA solutions was measured and, in the case of bound fatty acids, free fractions of SA were increased by up to 100%. In sharp contrast, the free fraction of SA present in sera from patients with arthritis who were on long-term aspirin (ASA) therapy was roughly twice that found in HSA solutions. A correlation between serum concentrations of free SA and albumin was evident in sera from one group of children with juvenile rheumatoid arthritis (r = -0.75) but was not seen in sera from the other patients. This would indicate that in vivo, the albumin level is not the sole, or, in some patients, even the dominant determinant of the free fraction of SA. Additional factors such as fatty acids and other hydrophobic ligands, both endogenous and exogenous, should be studied further, especially in adults.

Adult↗

PubMed1982

Aspirin survival in human blood modulated by the concentration of erythrocytes.

In vitro aspirin hydrolysis rates were measured in fresh human whole blood and in its separate components. The half-life of aspirin in whole blood was relatively rapid (mean 22.2 +/- 3.9 minutes) and exhibited a significant negative correlation with hematocrit (r = -0.96). Hydrolysis of aspirin in buffer that contained only washed red blood cells (40%) was significantly more rapid (mean half-life 17.5 +/- 2.0 minutes) than that in whole blood. When aspirin was incubated in solutions of washed red blood cells that contained human serum albumin in various concentrations, the aspirin half-life was found to vary directly with the concentration of albumin used; at normal levels of albumin, the hydrolysis rate of aspirin approximated that measured in whole blood. The presence of diisopropyl fluorophosphate in low concentrations (0.02-0.05 mM) markedly inhibited the rate of aspirin hydrolysis in washed red blood cells and whole blood. We conclude that enzymes(s) linked to the erythrocyte, probably membrane-bound acetylcholinesterase, control the survival of aspirin in blood.

Aspirin↗

PubMed1982

Erythrocyte membrane phosphatidylcholine and Rh (D) antigen cryolatency.

The extent of binding of anti-D antibody to intact RH (D) positive human erythrocytes at -2.5 degrees was approximately one-third that at 3- degrees. An Arrhenius plot of the temperature dependence of antibody binding showed a clear and reproducible discontinuity at approximately 6-8 degrees. Phospholipase A2 digestion of the intact erythrocytes resulted in a diminution of exclusively phosphatidylcholine (PC) from the membrane, and an approximately parallel loss of Rh antigen activity at 37 degrees to about 50% of the original. An Arrhenius plot showed no change in the temperature dependence below 6-8 degrees but significant diminution above that point suggesting that the outer membrane PC is involved in Rh (D) antigen activity manifested above that temperature.

Cold Temperature↗

PubMed1982

The binding characteristics of anti-Rho(D)-positive human and chimpanzee erythrocytes measured with 14C protein A.

The relation of the human erythrocyte Rho(D) antigen to its chimpanzee counterpart is currently unresolved. To explore this relation, we prepared 14C protein A to compare the binding parameters between human anti-Rho(D) and Rho(D)-positive human and chimpanzee erythrocytes. Double reciprocal plots of the binding in each case exhibited a straight line with intercepts indicating approximately the same numbers of Rho(D) binding sites for human and chimpanzee erythrocytes but an affinity that was 20 times greater for the human. This would indicate that the human and chimpanzee each have a single class of sites whose primary structure is very similar but sufficiently different to give the large divergence in affinity as measured by the human isoimmune antiserum.

Animals↗

PubMed1982

Induction of direct Coombs positivity with alpha-methyldopa in chimpanzees.

Two of four chimpanzees developed a moderately strong positive direct Coombs test after injection of stroma of their autologous erythrocytes that had been treated with alpha-methyldopa in the presence of diethyldithiocarbamate. Similar experiments with rabbits were unsuccessful. The results are concluded to be a demonstration that the first step in the development of autoantibody in alpha-methyldopa therapy is interaction of the oxidized drug with certain, as yet unidentified, peptides of the erythrocyte membrane.

Anemia, Hemolytic, Autoimmune↗