Significance of HLA and non-HLA antigens in bone marrow transplantation.
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Antibody-Dependent Cell Cytotoxicity↗
Biomedical subjects
A Saxon
Publications and source records attributed to A Saxon.
Immunologic characterization of hairy cell leukemias in continuous culture.
The immunobiologic characteristics of three continuous cell lines established from hairy cell leukemia cells were investigated. All three cell lines continued to produce tartrate-resistant acid phosphatase, the enzymatic marker of hairy cells. Two of these cell lines were B lymphoid in nature. They carried Fc and C receptors, had surface and internal immunoglobulin, and did not form spontaneous sheep red blood cell rosettes. Experiments employing biosynthetic radiolabeling of immunoglobulin demonstrated distinctive immunoglobulin kinetics for each of these two hairy cell lines. One cell line remained quite similar to the original hairy cells from which it was derived whereas the other B lymphoid hairy cell line had undergone a switch in the immunoglobulin isotype produced. The third hairy cell leukemia line was shown to be of thymic derivation. These cells formed spontaneous sheep red blood cell rosettes and did not carry Fc or C receptors. The spontaneous sheep red blood cell rosette-forming cells contained tartrate-resistant acid phosphatase. They did not possess surface on internal immunoglobulin and did not synthesize immunoglobulin in vitro. Hairy cell leukemia cells maintained in permanent cell culture retain their immunobiologic properties and offer the opportunity for indepth study of these unusual cells.
Acid Phosphatase↗
Fever of undetermined origin: role of cytomegalovirus and Epstein-Barr virus.
Roles of various infections, neoplasms and granulomatous diseases in fever of unknown origin were studied in 22 patients. Bacterial infections were responsible in seven (32 percent), herpes viruses in five (23 percent), neoplasms in four (18 percent) and granulomata in two (9 percent) cases. Patients with herpes infections had initially no clinical or routine laboratory clues to viral involvement, and were given an intensive workup for 5 to 15 days. The diagnosis was made on the basis of cytomegalovirus or Epstein-Barr virus lgM antibody titers.
Adolescent↗
Macroglobulinemia and hairy-cell leukemia.
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B-Lymphocytes↗
Cytomegalovirus retinitis secondary to chronic viremia in phagocytic leukocytes.
We studied the relationship between the duration and intensity of cytomegalovirus viremia, cytomegalovirus complement fixing antibody, and cytomegalovirus retinitis in 61 renal transplant recipients. Five (8%) patients had chronic viremia which lasted more than six months. Two of the five developed typical cytomegalovirus retinitis and a severe fungal infection after intensive viremia of more than 11 months' duration. Retinitis did not develop in 22 patients with short-term viremia. Infectious cytomegalovirus was largely associated with polymorphonuclear leukocytes, but the virus was associated with monocytes during the immature granulocytic response accompanying one patient's terminal illness.
Adult↗
Dual immune defects in nongranulomatous ulcerative jejunoileitis with hypogammaglobulinemia.
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Adult↗
Discomforting talk and speech disruptions.
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Anger↗
Lectin-dependent cellular cytotoxicity in man.
Human peripheral blood leukocytes are cytotoxic to 51Cr-labeled target cells provided phytohemagglutinin is present in the reaction mixture. The lectin-dependent cellular cytotoxicity (LDCC) phenomenon is characterized by (1) the short duration of the assay (2 to 4 hr), (2) revealing potential cytotoxic cells present in the cell preparation and excluding participation of mitogen-induced polyclonal activation of effector cells generated during prolonged assays used in mitogen-induced cytotoxicity, and (3) using nonerythrocyte target cells. The effector cells that mediate LDCC were characterized by several cell fractionation procedures. Fractionation of Ficoll-Hypaque separated peripheral blood leukocytes on polystyrene bead columsn or on nylon fiber columns which remove monocytes, granulocytes, and immunoglobulin-bearing leukocytes did not remove the LDCC activity. Polymorphonuclear leukocytes preparations were devoid of LDCC activity. Enrichment for T cells by E rosette sedimentation demonstrated that LDCC activity is present in both the T cell-enriched fraction and the non-T cell fraction. Nylon column eluted non-Ig-bearing cells which were subsequently depeleted of T cells by E rosette separation were LDCC positive. Depletion of Fc-bearing leukocytes on EA monolayers removed the LDCC activity. These results demonstrated that two populations of Fc-bearing cells of thymus and nonthymus origin mediate LDCC. Normal and malignant cells of immune and human origin were good targets in LDCC. The wide range of sensitive target cells in LDCC makes this test feasible in a completely autologous or syngeneic system. The significance of the LDCC phenomenon in assessing cell-mediated immunity is discussed.
Adult↗
Immunoglobulin synthesis in hairy cell leukaemia.
In vitro studies were performed with leukaemic cells from two patients with hairy cell leukaemia in order to define the nature and kinetics of immunoglobulin synthesis by the neoplastic cells. Both patients had clinically and morphologically well-defined disease and their cells contained abundant tartrate-resistant acid phosphatase. One patient had associated macroglobulinaemia. The hairy cells had B-lymphocyte characteristics as determined by fluorescent immunoglobulin staining and surface receptor properties. They synthesized monoclonal IgM and IgG respectively in vitro. The kinetics of immunoglobulin synthesis were different in cells from the two patients as measured by equilibration time, intracellular degradation, and secretion. Permanent cell lines were established with cells from these patients. The lines grow as typical B-lymphoblastoid cultures and continue to produce tartrate-resistant acid phosphatase and immunoglobulin. These studies unequivocally demonstrate the B-lymphocyte nature of the hairy cells in these patients and provide evidence for their clonal origin both in terms of immunoglobulin and enzyme synthesis.
Acid Phosphatase↗
Preservation of in vitro biological functions in regional lymph node lymphocytes in squamous head and neck cancer.
Regional lymph node lymphocytes from patients with squamous cancer of the head and neck were tested in vitro for their ability to proliferate in response to phytohemagglutinin, concanavalin A, and allogeneic stimuli in one-way mixed lymphocyte culture. Their ability to act as cytotoxic effectors in phytohemagglutinin-dependent cellular cytotoxicity was also evaluated, and all results were compared to normal lymph node or blood lymphocytes. The regional lymph node lymphocytes retained proliferative capabilities equal to those in control lymph nodes or blood, whereas they were unable to mediate phytohemagglutinin-dependent cellular cytotoxicity. However, this was not a tumor-related effect because normal lymph node lymphocytes were also ineffective in this assay. The failure of the regional immune response to control early tumor growth could not be accounted for by generalized nonspecific immunosuppression in regional lymph node lymphocytes, inasmuch as these cells demonstrated normal in vitro activity.
Adult↗
Regulation of immunoglobulin production in human peripheral bood leukocytes: cellular interactions.
The intercellular influences regulating immunoglobulin (Ig) synthesis by normal human peripheral blood leukocytes (PBL) were investigated in cells stimulated by pokeweed mitogen (PWM). This system was shown to be totally T lymphocyte dependent as purified B lymphocytes (less than or equal to 1% T lymphocytes) failed to make significant amounts of Ig. No evidence was obtained for an Ig class switch as all classes of Ig (IgM, IgG, IgA) were shown to be produced in increasing amounts over a 6-day time period. T lymphocytes demonstrated maximum helper effect when mixed with equal numbers of B cells. This helper effect was mediated through the dual mechanisms of increasing the number of B lymphocytes containing cytoplasmic Ig and by increasing the maturity of these B lymphocytes as demonstrated by an increasing Ig production per B lymphocyte. When present in higher numbers, T lymphocytes were also capable of suppressing Ig production. This T-mediated suppression was first evident as a decrease in the Ig produced per B lymphocyte (decreased maturity). With maximum T suppression Ig-containing B lymphocyte numbers were also diminished. T lymphocyte help was relatively independent of macrophages (phagocytic cells) and did not require DNA synthesis for expression. Both T help and suppression were shown to cross allogeneic barriers. Immature T lymphocytes (thymocytes) were incapable of mediating either activity. Normal human PBL contain T lymphocytes campable of mediating both T help and suppression and the Ig produced by PBL was shown to be the balance of these activities. This balance probably represent the participation of distinct T lymphocyte subpopulations analogous to the T helper (Ly 1+) and T suppressor (Ly 2+, 3+) populations in the mouse.
Adult↗
Lymphoid subpopulation changes in regional lymph nodes in squamous head and neck cancer.
Lymph nodes from 10 normal patients and regional lymph nodes (RLN) from 19 patients with squamous cancer of the head and neck were evaluated as to their lymphoid subpopulations. In comparison to normal lymph nodes, RLN from cancer patients demonstrated a marked increase in the proportion of cells with membrane immunoglobulin, the receptor for the third component of complement, and the receptor for the Fc portion of immunoglobulin G. The increased Fc receptor cells were not Fc-bearing thymus-derived lymphocytes, inasmuch as they separated with the non-sheep erythrocyte-lymphocyte rosette-forming population. The overall thymus-derived lymphocyte percentage in RLN was proportionally decreased. A transition from the normal lymph node composition to the altered lymphocyte profile seen in RLN was demonstrated on moving from distal lymph nodes to RLN within the lymphatic drainage of a tumor. Lymph nodes involved with tumor also showed the pattern of bursa equivalent cell population increases.
Adult↗
Human lymph node lymphocytes fail to effect lysis of antibody-coated target cells.
Human lymphocytes prepared from peripheral blood, lymph nodes, spleen and thymus were titrated for ability to mediate lysis of human target cells coated with rabbit anti target antibody. Lymphocytes from blood and spleen produced efficient lysis of targets in the presence of antibody. Lymph node cells and thymocytes were essentially non-reactive in this system. Lymph node preparations from non-cancer patients contained approximately 25% of non-T cells with receptors for Fc,C3 and/or Ig. Regional lymph nodes from patients with primary tumours contained 37-50% non-T cells by the same criteria. Failure of lymph node lymphocytes to effect lysis of antibody-coated targets did not therefore correlate with content of Fc or C3 bearing cells per se. The effector cell in antibody-dependent cytotoxicity in other systems has been shown to carry Fc and C3 receptors, but not surface Ig. This cell type appears to be absent or non-functional in human lymph nodes.
Antigen-Antibody Reactions↗
Histamine-receptor leucocytes (HRL). Organ and lymphoid subpopulation distribution in man.
The frequency of lymphoid cells with a membrane receptor for histamine was determined in various lymphoid organs in man using a histamine-rosette assay. Thymus had very low numbers of histamine-receptor cells while lymph node and peripheral blood had increasing percentages. Through a combination of cell separation techniques, we demonstrated that about one third (1/3) of peripheral blood B lymphocytes and macrophages carry histamine receptors. Immature B cells or null cells (E-rosette and membrane-immunoglobulin-negative) do not have this receptor. Only 10% of peripheral blood T lymphocytes formed histamine rosettes. That these histamine receptor T lymphocytes are a subpopulation representing the differentiated suppressor/cytotoxic T cells is suggested by evidence showing complete removal of histamine receptor T lymphocytes on nylon wool adherence columns. Thus, the histamine receptor is expressed on differentiated B and T lymphocytes and may serve as a marker for developed suppressor/cytotoxic T cells in man.
B-Lymphocytes↗
Autoimmune panleukopenia.
A patient with episodic panleukopenia involving neutrophilic granulocytes, monocytes and lymphocytes had recurrent bacterial infections and a circulating cytotoxin that injured primitive myeloid cells as well as differentiated granulocytes and mononuclear cells. The cytotoxin was an immunoglobulin with activity against mouse, as well as human, myeloid stem cells. Clinical remission during cyclophosphamide therapy was associated with disappearance of the circulating leukocytotoxin. Serum from a period of active disease was cytotoxic for the patient's own lymphocytes obtained during clinical remission. Absorption of cytotoxic serum with granulocytes removed activity against both granulocytes and lymphocytes. These studies suggest an autoimmune disease in man characterized by episodic granulocytopenia, monocytopenia and lymphocytopenia due to humoral antibody against non-HLA antigens shared by several hematopoietic cell lines.
Adult↗
Letter: Inhibition of platelet function by nitroprusside.
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Blood Platelets↗
Single step separation of human T and B cells using AET treated srbc rosettes.
A technique for the single step separation of human thymus derived (T) and Bursa equivalent (B) lymphocytes was developed. Density separation of B lymphocytes and T lymphocyte-sheep red blood cell (SRBC) rosettes on Ficoll-Hypaque was modified by pretreatment of the SRBC with 2 aminoethylisothiouronium bromide hydrobromide. This modification yielded significantly purer populations of T and B cells. Up to 15 X 10(7) were separated without increasing contamination allowing for the recovery of B lymphocytes as well as T lymphocytes in sufficient numbers to use in functional assays.
B-Lymphocytes↗
Platelet inhibition by sodium nitroprusside, a smooth muscle inhibitor.
The effects of sodium nitroprusside (N.P.), a pure smooth muscle inhibitor, on platelet function were studied. Platelet-rich plasmas (PRP) from normal controls and from patients receiving N.P. were studied in vitro for aggregation in response to adenosine diphosphate (ADP), epinephrine, and collagen. Platelet ADP release (release reaction) was also investigated. Normal platelets demonstrated marked inhibition of aggregation when incubated with N.P. for 3 min. Prolonging the incubation was without additional effect. ADP and ATP release from platelets in response to collagen was also inhibited. PRP from patients receiving nitroprusside at concentrations between 25 mug/min an 165 mug/min showed inhibition of aggregation when compared to findings prior to the administration of N.P. N.P. acts by inhibiting contractile proteins and thus platelet ADP release and aggregation may depend on contraction of platelet smooth muscle-like protein, thrombosthenin.
Adenosine Diphosphate↗