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Biomedical subjects

D N Hart

Publications and source records attributed to D N Hart.

At least 127 records · Page 7Linked to original sources
PubMed1987

Inhibition of natural killer-cell mediated cytolysis with monoclonal antibodies to restricted and non-restricted epitopes of the leucocyte common antigen.

Three monoclonal antibodies recognizing different epitopes of the leucocyte common molecule, CMRF-11 (against the restricted or B-220 leucocyte common molecule), CMRF-12 and CMRF-26 [each against a different epitope on the non-restricted or T200 leucocyte common (CD45) molecule], were tested for their effects on lymphocyte cytotoxicity. The individual monoclonal antibodies inhibited human natural killer cell-mediated cytolysis (NK-CMC) weakly, but a mixture of CMRF-11 + 12 + 26 antibodies inhibited cytolysis more consistently and to a greater extent. This mixture did not inhibit cytotoxic T lymphocytes derived from secondary mixed lymphocyte cultures. The CMRF-11 + 12 + 26 mix was shown to inhibit a post-conjugate formation stage of lysis at the effector cell level. Inhibition of NK-CMC of a wide range of target cells, including the T-cell lines Jurkat, HSB2 and Molt 4, was demonstrated.

Antibodies, Monoclonal↗
PubMed1986

B cell lymphoma presenting as carcinoma of the lung.

A patient presented with superior vena caval obstruction caused by a tumour which resembled carcinoma of the lung both clinically and histologically. However, immunologic and cytogenetic analyses carried out on the mediastinal biopsy and on pleural fluid revealed that the tumour was of B cell origin, Burkitt-like in sub-type, and had the t(8;14) translocation. The nature of many poorly differentiated tumours may be more clearly identified with the help of immunological and cytogenetic analyses.

Antigens, Neoplasm↗
PubMed1986

Allogeneic bone marrow transplantation at Christchurch 1979-1985.

Twelve bone marrow transplants have been carried out at Christchurch since 1979 in five patients with aplastic anaemia and seven with acute leukaemia. Five patients are currently alive at 77, 69, 63, 45, and seven months post-transplant. Acute and chronic graft versus host disease have been major problems and its clinical features and management are described. Long term follow-up data is presented on the four patients currently alive at between three to six years post-transplant. The practical problems we have experienced by carrying out bone marrow transplants without special funding have been considerable and the implications of this are discussed.

Adolescent↗
PubMed1986

The inheritance of abnormal sialoglycoproteins found in a Gerbich negative individual.

The Gerbich blood group antigens are probably expressed on one or more of the minor erythrocyte (beta, beta 1, or gamma) sialoglycoproteins which are lacking in some rare individuals having the Gerbich negative phenotype. A monoclonal antibody, CMRF-10, which recognises a trypsin-sensitive site on both the beta and beta 1 sialoglycoproteins, was tested for binding to erythrocytes from a Gerbich negative individual, OM. Erythrocytes from OM bound CMRF-10 in similar amounts to normal erythrocytes even though membranes from OM were shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis to lack both the beta and gamma sialoglycoproteins found in normal red blood cells. Instead, abnormal sialoglycoproteins which migrated as two bands with apparent molecular weights within the range 29,500-32,500 daltons were identified and purified using CMRF-10. Subsequent electrophoretic analysis of OM's two children failed to reveal any abnormal sialoglycoproteins. This suggests that in this instance the Gerbich negative phenotype may result from other mechanisms, possibly defective glycosylation, rather than a crossover involving the gene coding for the primary protein structure of the sialoglycoproteins.

Aged↗
PubMed1984

The effect of donor pretreatment on interstitial dendritic cell content and rat cardiac allograft survival.

Different pretreatment schedules were applied to rat heart donors and their effect on heart interstitial dendritic cell content was observed using monoclonal antibodies and immunofluorescence techniques. Interstitial dendritic cell (IDC) numbers were correlated with the histology and survival of hearts transplanted into untreated allogeneic recipients. Hearts from AS donors pretreated with cyclophosphamide and total-body irradiation showed prolonged survival in DA recipients only when more than 95% of the graft interstitial dendritic cells were depleted. Reconstitution studies established that prolonged graft survival following donor pretreatment depended on the removal of bone-marrow-derived cells and that these were IDCs. These results suggest that the IDC is the most significant "passenger leucocyte", and that very small numbers of residual IDCs were still sufficient to cause rapid rejection. DA rat heart contained three times as many IDCs as the AS strain and DA hearts were much more difficult to deplete of IDCs. Pretreated DA hearts were rejected by AS recipients, although grafts with a lower IDC content resulted in an attenuated histological rejection response and a markedly decreased recipient lymphocytotoxin response. To be effective, donor pretreatment schedules had to be initiated 5 days prior to transplantation. Pretreatment 6 hr prior to transplantation failed to deplete IDC or prolong graft survival even in he weak (ASxDA)F1 to DA model. Pretreatment protocols used clinically have probably not removed IDCs adequately and the development of methods that deplete IDCs effectively could improve graft survival at no risk to the recipient.

Animals↗
PubMed1983

Major histocompatibility complex antigens in the rat pancreas, isolated pancreatic islets, thyroid, and adrenal.

Monoclonal antibodies to rat class I and class II MHC antigens have been used with the peroxidase-antiperoxidase technique to localize these antigens in the DA rat pancreas, isolated pancreatic islets, adrenal, and thyroid tissue. The class I (RT1A) antigens were found to be expressed by pancreatic islet cells, adrenal cortical cells, thyroid follicular cells, and--in low concentration--on cells of the adrenal medulla. These same cells did not express class II (Ia or RT1B) antigens. However, interstitial dendritic cells, staining intensely for class II antigens were present in thyroid, adrenal and pancreatic tissue, and within isolated pancreatic islets. These cells probably represent the immunogenic passenger leukocyte.

Adrenal Glands↗
PubMed1981

Demonstration and characterization of Ia-positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, but not brain.

In this study, we have used a mouse monoclonal antibody to rat Ia (RT1-B or class II) antigens to demonstrate, by immunofluorescence on frozen sections, intensely Ia-positive dendritic cells in the interstitial connective tissues of every tissue we have examined (heart, liver, thyroid, pancreas, skin, kidney, ureter, and bladder) with the striking exception of brain. The characteristics of the interstitial dendritic cell found in heart were studied in detail, and this cell was shown to be negative for acid phosphatase, beta-glucuronidase, and ATPase activity, and certainly some and probably all of the cells were negative for nonspecific esterase activity. Experiments with colloidal carbon suggested that the cell was either poorly or not at all phagocytic. The cells were negative for surface immunoglobulin and the W3/13 antigen, but positive for the leukocyte common antigen and the SD (Class I) antigens of the major histocompatibility complex. The cell was shown to be of bone marrow origin, and either the cell itself, or more probably its precursor, was shown to be sensitive to irradiation and to cyclophosphamide. All strains tested--including the nude rat--had large numbers of interstitial dendritic cells. The widespread distribution, except in brain, of this cell, which resembles in every respect the dendritic cell described by Steinman et al. (4) in the spleen and lymph nodes of the mouse, is of interest, and the implications in this finding are discussed.

Animals↗
PubMed1981

Antibody response after alloimmunization with heart tissue in the rat. Characterization of the autoantibodies.

LEW antisera to DA heart homogenate or DA vascularized allografts were studied using 125I anti-immunoglobulin binding assays with heart homogenate as the target tissue. In this way, the full spectrum of antibodies generated could be studied. In both sera, the main antibody generated was autoantibody directed at antigens found in highest concentration in heart tissue. These autoantibodies were readily demonstrated in binding assays using heart homogenate as target, but were not detected in binding or cytotoxicity assays with lymphocyte suspensions as targets. Immunofluorescence studies showed that the autoantibody response was complex. The autoantibodies in the antihomogenate serum were strong and were directed primarily at intracellular components found in the myocardial cells, the bases of the tubular cells in the kidney, and type I skeletal muscle fibers, and were possibly directed at mitochondria. The antigraft serum was weaker and contained, in addition to the putative antimitochondrial autoantibodies, autoantibodies directed at the intercalated discs. In addition, a component of the antibodies was directed at alloantigens and this is discussed in the succeeding paper.

Animals↗
PubMed1981

Antibody response after alloimmunization with heart tissue in the rat. Characterization of the alloantibodies.

The autoantibody component of LEW anti-DA heart homogenate serum was removed by exhaustive absorption with LEW heart, and the remaining alloantibody component assayed on DA heart homogenate target using 125I antirat immunoglobulin binding assays. The alloantibodies could be divided into two components, one present on spleen and presumably directed at major histocompatibility complex (MHC) antigens and the other present on heart but absent from spleen, liver, and kidney, and therefore defining a heart-specific alloantigen. Localization studies on frozen sections showed the antigen to be localized to the membrane and T tubular system of the myocardial cells and also to the membrane of skeletal muscle cells. Backcross studies showed that the locus coding for this heart-specific antigen appeared not to be linked to the MHC, and that the MHC was the only locus of importance for acute rejection of heart grafts in the DA to LEW combination. Thus, it was concluded that the heart-specific alloantigen was not important for acute cardiac rejection at least in the DA to LEW rat strain combination. As regards antibodies to MHC antigens, there appeared to be substantially more of these in LEW anti-DA heart graft serum when compared to LEW anti-DA heart homogenate serum, and both anti-SD (RT1.Aa) and anti-Ia (RT1.Ba) antibodies could be demonstrated in the antiheart graft serum.

Animals↗
PubMed1981

Antibodies to liver-specific auto- and alloantigens after alloimmunization with liver tissue in the rat.

LEW anti-DA liver homogenate and anti-DA liver vascularized graft sera were studied using 125I anti-immunoglobulin binding assays with liver homogenate as the target tissue. In both cases, a major component of the antibodies generated was autoantibody directed at a liver-specific antigen localized intracellularly in hepatocytes. These autoantibodies could not be detected by binding or cytotoxicity assays on lymphocyte targets. In addition, a component of the antibodies was shown to be directed against a liver-specific alloantigen located on the external and intracellular membranes of hepatocytes, and coded for by a locus not linked to the major histocompatibility complex (MHC). Alloantibodies were also demonstrated to both SD-type (RT.1A) and Ia-type (RT.1B) antigens of the MHC, with a preponderance of anti-SD antibodies.

Animals↗
PubMed1981

Major histocompatibility complex antigens in rat kidney, ureter, and bladder. Localization with monoclonal antibodies and demonstration of Ia-positive dendritic cells.

Monoclonal mouse xenoantibodies to the SD and part of the Ia antigen complex of the rat major histocompatibility complex (MHC) were raised, and used to localize MHC antigens on frozen sections of kidney, ureter, and bladder of the DA rat strain. The Ia antigens recognized by our monoclonal antibody were located almost entirely within the cells of some, probably the proximal, convoluted tubules of the kidney. The only other Ia-bearing structures were intensely Ia-positive dendritic cells found predominantly in the renal cortex and in the mucosal connective tissues of the ureter and bladder. The SD antigens were widely distributed in the kidney with a major portion again located within the tubular cells, although in the case of SD antigens all tubular cells, including those of the medulla, were positive. By far the brightest tubules were clusters in the outer medulla, probably representing the thick loops of Henle. The endothelium of arterioles, venules and glomerular and interstitial capillaries all stained very brightly for SD antigens. The glomerular mesangium and the interstitial connective tissues of the kidney, ureter, and bladder all gave diffuse positive staining for SD antigens. Transplantation studies established that the tubular Ia and SD antigens of the kidney are produced by the cells and are not in the process of excretion or reabsorption.

Animals↗