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Biomedical subjects

S Granger

Publications and source records attributed to S Granger.

13 recordsLinked to original sources
PubMed1995

Elastomeric valves, a new design.

The convex bileaflet valve replaces the flat biflap inflow valve designed by Long Sheng Yu and the tricusp semilunair outflow valve. One reason is easier manufacturing. Convex bileaflet valves are developed for the 11, 20, 40, 70 and 140cc ventricles. Testing included curves (Cardiac Output versus Venous Pressure, Cardiac Output versus Heart rate), flow visualization studies, paint and bloodbag studies. The curves and flow visualization were done by connecting ventricles to one of our standard mock circulations. Paint and bloodbag studies were done by connecting the hearts to a bloodbag, but the bag was filled with water for the paint studies. The curves show high cardiac output, even with pumping at high heart rates (150 BPM+). The flow visualization shows a good stream through the sinus Valsalvae. No stagnating flow is visible. The bloodbag studies which provoke thrombosis show it on the edges of the heart valves, and little in the groove between the valve and the sinus Valsalvae. Heparninzation prevents the thrombosis. Results of our tests were good. The convex bileaflet valve seems to have good future.

Biocompatible Materials↗
PubMed1982

Elimination of T-lymphocytes from human bone marrow with monoclonal T-antibodies and cytolytic complement.

Complement-mediated cytolysis has been used to remove T-lymphocytes from suspensions of human peripheral blood and bone marrow. Selective T-cell removal was investigated by three monoclonal antibodies. OKT3, MBG6 and OKT11A. All three removed greater than 90% of T-cells but combinations were necessary to kill greater than 99% of T-cells in vitro. The macrophage-granulocyte and erythroid colony forming cells of the bone marrow were spared. The method can be applied on bulk BM samples during clinical BM transplantation and will be useful to establish whether the virtually complete removal of T-lymphocytes totally prevents transplant associated graft-versus-host disease in man.

Antibodies, Monoclonal↗
PubMed1982

Distribution of terminal deoxynucleotidyl transferase and purine degradative and synthetic enzymes in subpopulations of human thymocytes.

Terminal deoxynucleotidyl transferase (TdT) and purine metabolic enzymes were examined in subsets of human infant thymocytes (defined by surface cell antigens) and normal peripheral T lymphocytes. Putative prothymocytes (RFB-1+, HTA-1+/- large blast-like cells), medium and high density cortical thymocytes (RFB-1+, HTA-1+), and medullary thymocytes (RFB-1-, HTA-1-, OKT3+) were isolated by density gradient centrifugation, monoclonal antibody and complement-mediated cytolysis, and cell-antibody affinity chromatography. Peripheral T lymphocytes were isolated from normal adult mononuclear cells using nylon fiber technique. Adenosine deaminase (ADA) and TdT were highest in prothymocytes 48.8 +/- 14.7 mumol/hr/10(8) cells (mean +/- SE) and 22.9 +/- 1.4 U/10(8) cells, respectively. Both enzymes decreased progressively down the maturation pathway. In peripheral T lymphocytes, ADA was 3.9 +/- 1.5 mumol/hr/10(8) cells, and TdT was undetectable. Purine nucleoside phosphorylase (PNP) and ecto-5'nucleotidase (5'NT) were lowest in cortical thymocytes (27.5 +/- 11.0 nmol/hr/10(6) cells and 2.8 +/- 1.3 nmol/hr/10(6) cells, respectively) and increased with T cell maturation. The PNP level was 124.9 +/- 17.2 nmol/hr/10(6) cells and 5'NT was 30.1 +/- 3.9 nmol/hr/10(6) cells in peripheral T lymphocytes. The deoxynucleoside kinases (deoxyguanosine, deoxyadenosine, and deoxycytidine kinases) paralleled the changes in ADA and TdT activity among the different T subsets. The proliferative activity (labeling index) was highest in the prothymocyte fraction and lowest in peripheral T cells. Variation in the distribution of these enzymes in T cell subsets may explain their different sensitivities to deoxyadenosine and deoxyguanosine toxicity and the different effects on T cell development of ADA or PNP deficiency.

Adenosine Deaminase↗
PubMed1982

T cell subset abnormalities in tissue lesions developing during autoimmune disorders, viral infection, and graft-vs.-host disease.

The authors review a large body of contemporary immunohistologic findings on the tissue distribution of T lymphocytes in normal and pathological conditions. The suggestions for technological advances in this field are: signal amplification using mixtures of monoclonal antibodies directed against different epitopes on the same antigen (e.g. OKT4A+B+D), triple layer amplification systems using hapten-labelled antibodies, and informative double staining methods with combinations of antibodies labelled with different fluorochromes or enzymes. Review of histological observations in a series of human diseases suggests that imbalances of OKT4+ and OKT8+ subsets of T lymphocytes may represent different types of immunoregulatory disorders. Rheumatoid arthritis and sarcoidosis appear to involve a high level of OKT4+ subpopulation response coupled with an associated appearance of a special type of HLA-DR+ macrophages. It remains to be seen whether normal or self-limited immunological responses (early stages of bacterial infection or delayed-type hypersensitivity reactions) produce OKT4+ and macrophage responses that are characteristically different. Meanwhile, excessive levels of OKT8+ cells have been found in a wide range of recognized or presumed immunoregulatory disorders including: graft-vs.-host reaction and viral infections. These disorders, as well as primary biliary cirrhosis and lichen planus, appear to possess both overlapping and disparate clinical characteristics, and the immunohistological observations may reflect the functional heterogeneity of OKT8+ populations in these diseases. These studies show that histologically meaningful heterogeneity can already be demonstrated for the OKT8+ lymphocyte group.

Animals↗
PubMed1982

Distinct T lymphocyte subsets affect granulo-monocytic differentiation and proliferation.

Bone marrow culture techniques using semi-solid support-media provide an opportunity to observe granulocyte-macrophage progenitor cells proliferating and differentiating in vitro. Cells from the bone marrow and peripheral blood produce specific growth factors which stimulate both the proliferation and differentiation processes (collectively termed colony-stimulating factors or activity, CSF/CSA). Even highly purified CSA induces proliferation and concomitant differentiation suggesting that the two processes are inseparable. We here present evidence to suggest that the two processes are, at least in part, individually regulated. We observed delayed differentiation by morphological, cytochemical and functional criteria in granulocyte-macrophage clones formed in cultures in which the growth stimulus was supplied by marrow or blood cells which have been depleted of T lymphocytes bearing the OKT3/MBG6 antigen(s) by complement lysis. The proliferation stimulus was unaffected. T cell depletion using another monoclonal antibody, OKT11a (which removed an overlapping but not identical population of T cells), did not produce the same effect but did increase the level of CSA produced by the remaining marrow cells. Selective replacement experiments using OKT4+ or OKT8+ cell preparations suggested that removal of an MBG6+, OKT3+, OKT8+, OKT4-lymphocyte subset is responsible for the effect on differentiation.

Antibodies, Monoclonal↗
PubMed1981

Delineation of human thymocyte differentiation pathways utilizing double-staining techniques with monoclonal antibodies.

Three new techniques have been introduced for the phenotypic analysis of human thymocytes and T cells. Monoclonal antibodies of different subclasses (i.e. IgG1 and IgG2) were used in various combinations and labelled with subclass-specific second layers conjugated to different fluorochromes. Tissue sections were studied with combinations of monoclonal and conventional reagents, and anti-mouse Ig-coated macrobead columns were used to separate antibody-tagged cells. With the help of these simple techniques, four stage of thymocyte differentiation (prothymocyte, cortical, intermediate and medullary cell types) can be described in detail and the microanatomical relation of T cell subsets with other cell types studied.

Antibodies, Monoclonal↗
PubMed1981

Recognition of a human T-lymphocyte differentiation antigen by an IgM monoclonal antibody.

A monoclonal antibody directed at a determinant on human T cells was produced and characterized. This IgM antibody, MBG6, bound to human peripheral blood T lymphocytes and to medullary thymocytes. It was unreactive with normal B cells, B-cell lines and granulocytes. Apart from T lymphocytes, bone marrow cells (including cells positive for the terminal transferase marker, myeloid colony-forming cells, myeloblasts, and differentiating myeloid and erythroid cells) were negative. Peripheral blood cells that were treated with MBG6 and rabbit complement were no longer capable of proliferating in response to phytohaemagglutinin or concanavalin A; MBG6 did not have any direct mitogenic action on T lymphocytes. Double immunofluorescence studies using IgM MBG6 and OKT3, and IgG2a monoclonal antibody that recognizes all peripheral T cells, showed that these two antibodies identified exactly the same cell populations. Competitive binding studies, however, indicated that MBG6 and OKT3 recognized different epitopes. The antibody may have clinical applications in bone marrow transplantation.

Animals↗
PubMed1977

Bone marrow cellularity determination: comparison of the biopsy, aspirate, and buffy coat.

Bone marrow biopsies (244) performed with a Jamshidi needle were evaluated in 53 children with leukemia or aplastic anemia. Adequate specimens were obtained in 85%. Results of cellularity estimated by biopsy were compared to the cellularity of the aspirate versus volumetric determination of the myeloid-erythroid layer (buffy coat). A wide discrepancy was noted between marrow cellularity confirmed by biopsy versus the aspirate or buffy coat. The greatest variance was seen in the hypercellular or normocellular marrows, as estimated by biopsy, in which 39% were misinterpreted as moderately or severely hypocellular by aspirate. Volumetric measurement of buffy coat was least acceptable for estimating cellularity. Thus the biopsy has proved to be an important and reliable indicator of bone marrow cellularity.

Anemia, Aplastic↗