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Biomedical subjects

D Allan

Publications and source records attributed to D Allan.

At least 127 records · Page 7Linked to original sources

Microvesicles from sickle erythrocytes and their relation to irreversible sickling.

Incubation of sickle (HbS) erythrocytes for periods up to 96 h leads to the formation of irreversibly sickled cells (ISCs) and to the release of spectrin-free microvesicles similar to those derived from aged or Ca2+-ionophore-treated normal erythrocytes. The sickle microvesicles were somewhat larger than those from normal cells and showed minor differences in their membrane polypeptide composition. Sickle microvesicles were no different from their parent cells in their content of fetal haemoglobin. Neither microvesiculation nor formation of irreversibly sickled cells required the presence of Ca2+ in the medium but Ca2+ did accelerate both processes. Although in these prolonged incubations microvesiculation appeared to occur concomitantly with the formation of ISCs, it is not clear whether or not microvesiculation is a necessary prelude to irreversible sickling.

Anemia, Sickle Cell↗

A study of immunoregulation of BALB/c mice by Echinococcus granulosus equinus during prolonged infection.

Two models of intraperitoneal infection with E. granulosus equinus by protoscolices and by cyst passage in BALB/c mice were used to provide mesenteric lymph node cells for adoptive cell transfer into syngeneic recipient normal responder mice. The cell transfer inocula were shown to have depleted Thy-1 cells, but to be highly suppressive to the normal sheep erythrocyte response of the recipients. The nature of the depletion and non-specific suppression, and the infectious nature of the latter, are discussed in relation to other examples of mitogenic stimulation resulting in non-specific T cell suppressor activity. The functions of Ly-2,3+ cells, not only as suppressor, but as alloreactive cytotoxic cells, are discussed as a possible, autoimmune explanation for the longevity of the parasite within the mouse model, in contradistinction to the predictable early rejection of analogous xenografts.

Animals↗

A synthetic ionophore for Ca2+: studies with model and biological systems.

We show that the relatively simple beta-diketone, 1.1.1.2.2.3.3-heptafluoro-7,7-dimethyloctane-4,6-dione, known as "fod", will solvate Ca2+ ions in an organic phase. In consequence it will transport Ca2+ across phospholipid bilayers. It acts as predicted for a Ca2+-transporting ionophore in two biological systems: it will stimulate Ca2+-dependent K+ efflux from human red blood cells, and Ca2+-dependent histamine secretion from rat peritoneal mast cells.

Animals↗

1,2-diacylglycerol kinase of human erythrocyte membranes. Assay with endogenously generated substrate.

1,2-Diacylglycerol kinase activity was measured in human erythrocyte membranes using an assay procedure in which the substrate was generated endogenously, either by treatment with a bacterial phospholipase C or by incubation with Ca24, which activates a membrane-bound polyphosphoinositide phosphodiesterase. The properties of 1,2-diacylglycerol kinase were broadly similar to those described previously, except that in the present work maximum activities were higher and there was evidence for a double pH optimum.

Calcium↗

The isolation and characterization of 60 nm vesicles ('nanovesicles') produced during ionophore A23187-induced budding of human erythrocytes.

In addition to the microvesicles released during the treatment of human erythrocytes with Ca2+ and ionophore A23187, a new subpopulation of still smaller dense vesicles ('nanovesicles') has now been identified. Nanovesicles are about 60 nm in diameter, have an acetylcholinesterase activity higher than that of microvesicles and appear to be relatively enriched in sphingomyelin and correspondingly depleted of phosphatidylethanolamine. They have a polypeptide composition quite different from those of erythrocyte membranes or microvesicles, consisting largely of components of mol.wts. 60 000 and 26 000 in addition to haemoglobin. These two major polypeptides do not appear to represent contaminating cytoplasmic proteins or proteolytic subfragments of a larger protein.

Anti-Bacterial Agents↗

Disseminated histoplasmosis presenting with oral lesions - report of a case.

A case of disseminated histoplasmosis is presented in which the initial diagnosis was made on the histology from oral lesions. The clinical and microscopical differential diagnoses are discussed. Including the present case, 12 of the 13 subjects with disseminated histoplasmosis initially diagnosed in Great Britain have given a history of residence in an area where the disease is endemic. Many years of good health may intervene between the original infection and its subsequent reactivation. A diminished cellular immune response may precipitate this reactivation but could also facilitate the possibility of exogenous reinfection. The literature is reviewed.

Diagnosis, Differential↗

The relationship between Ca2+-mediated polyphosphoinositide phosphodiesterase activity, 1, 2-diacylglycerol accumulation, and microvesiculation in erythrocytes.

A variety of morphologic and metabolic changes occur in erythrocytes in which the intracellular level of Ca2+ is increased. These include echinocytosis followed by microvesiculation, K+ efflux, ATP degradation, and activation of polyphosphoinositide phosphodiesterase with the formation of 1,2-diacylglycerol and phosphatidate. The relationships between these changes are discussed and an attempt is made to assess their significance in both normal and aged cells.

Adenosine Triphosphate↗

Haematological correlates of phytohaemagglutinin-induced lymphocyte transformation in horses.

The purpose of these investigations was to assemble and compare data which might illustrate a functional relationship between phytohaemagglutinin-induced transformation of equine lymphocytes in vitro and the haematological profiles of the lymphocyte donors. Statistically significant correlation between transformation and a haematological parameter was taken as evidence that both may be part of a common regulatory system. There was no evidence that transformation in vitro was affected by artefactual variation in the cellular composition of the cultures. Transformational behaviour of lymphocytes in autologous plasma showed significant correlation with donors' total leucocyte, neutrophil and T cell count. Different batches of donor plasma varied in ability to support the transformation and this ability was found to correlate significantly with the total leucocyte, eosinophil, lymphocyte and T cell count of the original blood. It is concluded that previously reported variation in transformation ratios of normal equine lymphocytes is attributable to regulatory mechanisms affecting circulating blood as a whole and that helminth parasitism may be among the primary causal agents which modify the mechanism.

Animals↗

A calcium-activated polyphosphoinositide phosphodiesterase in the plasma membrane of human and rabbit erythrocytes.

Haemoglobin-free human erythrocyte ghosts that were prepared in the presence of EDTA and were then exposed to Ca2+ showed a substantial loss of phosphatidylinositol phosphate and phosphatidylinositol diphosphate, measured either chemically or by loss of 32P from the lipids of prelabelled membranes. At the same time there was, as reported previously (Allan, D. and Michell, R.H., (1976) Biochim. Biophys. Acta 455, 824--830), and approximately equivalent rise in the diacylglycerol content of the membranes. Analysis of the 32P-labelled water-soluble material released during this process showed that the major products were inositol diphosphate and inositol triphosphate. No change was seen in the phosphatidylinositol or phosphatidate content of the membranes, and there was no Ca2+-activated loss of 32P from the phosphatidate of prelabelled membranes: this suggests that Ca2+ did not activate phosphoinositide phosphomonoesterases or phosphatidate phosphomonoesterase in human erythrocyte membranes. It is concluded that human erythrocyte membranes contain at their cytoplasmic surface a Ca2+-activated phosphodiesterase that is active against both phosphatidylinositol phosphate and phosphatidylinositol diphosphate. Rabbit erythrocytes also contained this enzyme, but in these cells there was also evidence for the presence of a Ca2+-activated phosphatidate phosphomonoesterase.

Animals↗

In vivo studies on suppressor lymphocyte activity following administration of Escherichia coli O138 lipopolysaccharide.

Evaluation of Escherichia coli vaccines used in veterinary practice usually relates to antibody formation and neglects the essential characteristics of cell function leading to this end. This paper attempts to investigate the cellular responses to E coli O138 lipopolysaccharide (LPS) administered subcutaneously in a dose range of 1 microgram to 200 microgram. Rosette-forming cell responses in the draining lymph node varied from antigenic at 10 microgram to tolerogenic at 200 microgram. The tolerogenic dose also caused a marked mitogenic response as can be seen by a fourfold increase in total lymph node cells. Fractionation of normal or LPS-responding, or LPS-tolerised lymph node cells into B cell-rich and T cell-rich fractions was carried out and these were adoptively transferred simultaneously with an antigenic dose of sheep erythrocytes (SRBC) into syngeneic recipient mice. Suppressor activity of the anti-SRBC response was found after transfer of 1 X 10(6) normal B cell fractions, 1 X 10(6) tolerised B cell fractions and 1 X 10(6) tolerised T cell fractions. LPS-antigenically stimulated lymph node cell fractions had no suppressor effect but when given with Freund's complete adjuvant ensuing T cell-rich fractions produced immunosuppression in recipient mice. The significance of these findings is discussed in relation to polyclonal B cell activation, helper and suppressor T cells, and possible feedback mechanisms between interacting subpopulations of lymph node cells.

Animals↗

Tolerance breaking by lymphocyte activating factor induced by Escherichia coli O138 lipopolysaccharide from homologous macrophages.

Following an antigenic dose of 10 microgram or a tolerogenic dose of 200 microgram of Escherichia coli O138 lipopolysaccharide (LPS), BALB/c mice were examined on day 14 for percentages of theta-bearing cells. A considerable increase in T cells was noticed in lymphocytes from tolerant draining lymph nodes, and furthermore these cells did not possess receptors for LPS when tested for rosette inhibition. However, when the supernatant from 1 X 10(7) macrophages, pretreated with 150 microgram LPS, was given to tolerant mice on day 7, by day 14 tolerance was found to be broken, anti-LPS IgG was present in circulation and the draining lymph node contained T cells specifically committed to LPS. The change from suppressor to helper T cell activity is discussed in relation to enhancement of the immune response.

Animals↗