To purge or not to purge: the neuroblastoma experience.
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Bone Marrow↗
Biomedical subjects
Y Gazitt
Publications and source records attributed to Y Gazitt.
Clinical and flow cytometry characteristics of malignant pleural effusions in patients after intracavitary administration of methylprednisolone acetate.
Ten patients with recurrent pleural effusions due to advanced cancer were treated by intracavitary methylprednisolone acetate (Depo-Medrol [DM], Upjohn, Kalamazoo, MI). They received one to six courses of DM (median, three courses per patient) with doses ranging from 80 to 160 mg per course. Effusion cells were cryopreserved before and during DM installation for subsequent determination of ploidy by flow cytometry. Pleural effusion in all three patients with advanced breast cancer resolved and did not reaccumulate throughout follow-up for 11+, 10+, and 8+ months. Pleural effusion in a patient with metastatic gastric cancer and in two of four patients with adenocarcinoma of unknown origin partially resolved. Altogether six of ten patients (60%) subjectively and objectively benefited from this therapy. All patients tolerated the treatment well with no local or systemic side effects. Flow cytometry showed a reduction in ploidy of effusion cells in all three patients with breast cancer, from a peak mean channel of 6C to nearly 2C after therapy. Transient reduction of ploidy was seen also in the effusion of a patient with unknown primary tumor associated with clinical improvement. The clinical and laboratory data reported offers initial evidence that DM when instilled into the pleural cavity after incomplete thoracentesis may act as effective palliative therapy either alone or in combination with other anticancer agents.
Adult↗
Down-regulation of bone marrow stem cell formation by T cell subsets. Effect of CD8+ cells on colony formation in peripheral blood and bone marrow.
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Antigens, CD↗
Electro-insertion of xeno-glycophorin into the red blood cell membrane.
The electroporation technique, with field strengths slightly below the critical value Ec for electroporation of red blood cells (RBC), enables the insertion of xeno-proteins into the RBC membrane without damaging the cells. The electro-insertion has been used to insert biotinylated human glycophorin into human RBC membrane and human glycophorin into murine RBC membrane. Binding anti-human glycophorin antibody (10F7) to the murine RBC bearing human glycophorin indicates extracellular orientation of inserted glycophorin. Insertion of about 10(5) glycophorin molecule per cell has been estimated by whole cell ELISA.
Animals↗
Improvement of immune-complex nephritis associated with hepatitis B surface antigen excess.
A case of hypocomplementemic membranoproliferative glomerulonephritis was studied during remission of nephrosis induced by high doses of corticosteroids. Hepatitis B surface antigen (HBsAg) and immune complexes were detected in serum and glomeruli. Anti-hepatitis-B surface antibody, undetectable in serum by conventional radioimmunoassays was identified in circulating immune complexes (CIC). On two occasions, improvement in renal function coincided paradoxically with an extreme increase in serum HBsAg levels as well as with marked elevation of CIC. We suggest that, as previously observed in animal models of glomerulonephritis, extreme antigen excess may inhibit glomerular deposition of immune complexes.
Antigen-Antibody Complex↗
Induction of surface marker changes and monoclonal idiotypic immunoglobulin secretion in lymphoma/leukemia cells: comparative study with interleukin-1, interleukin-2, interleukin-4, 8-bromo-guanosine, pokeweed mitogen, and tetradecanoyl phorbol-13-acetate.
Induction of differentiation in B lymphoma/leukemia cells with interleukins was compared with differentiation induced by phorbol ester (TPA) and pokeweed mitogen (PWM) or by 8-bromo-guanosine. Both cell surface changes and monoclonal immunoglobulin (Ig) secretion were followed as markers of differentiation. The results indicate great similarity in the differentiation patterns induced by interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-4 (IL-4), with regard to Ig secretion and changes in surface markers. Induction of Ig secretion and surface marker changes by 8-bromo-guanosine was similar to that induced by TPA and PWM; however, for some markers, cell surface changes induced by TPA and PWM or by 8-bromo-guanosine were quite different from those induced by the three interleukins tested. Whereas all three interleukins stimulated the expression of CD5, PWM and TPA and 8-bromo-guanosine substantially decreased CD5 expression on B lymphoma cells. Differences were also observed in the effect on the expression of surface Ig and on the expression of CD19 and CD20. Interestingly, the three interleukins tested and 8-bromo-guanosine induced differentiation and Ig secretion within 24 to 48 hours with no prior activation by B-cell activators, such as anti-surface Ig antibody. These results suggest that leukemic B cells are arrested at a point distal to activation and first cell division. Moreover, the similarity in Ig secretion and surface changes induced by TPA and PWM or 8-bromo-guanosine suggest a similar pathway; however, this pathway is different from the differentiation signal induced by the three interleukins.
Antibodies, Monoclonal↗
Establishment and characterization of a malignant lymphoid cell line from a chronic lymphocytic leukemia patient.
A long-term culture Epstein-Barr virus (EBV)-negative malignant lymphoid cell line (NAK) was established from a lymph node biopsy of a chronic lymphocytic leukemia patient. This cell line is of particular interest because it grows as an adherent cell line and depends on the presence of autologous conditioned medium for growth. After 6 months of growth in vitro, doubling time and cell cycle parameters were derived. Doubling time was 48 hours with over 45% cycling cells. Cell viability was over 90%. Expression of B-cell markers (CD19 and CD20) and surface immunoglobulin of the original tumor cell biopsy were roughly the same as in passage 14 (3 months in culture), including the expression of the original patient idiotype and IgM-lambda. Furthermore, binding of antiidiotypic antibodies was only slightly decreased at passage 14. Cytogenetic studies of chromosomal abnormalities in the primary tumor tissue and in later passages indicated similar abnormalities, with no translocations t(8;14), t(14;22), or t(2;8). However, frequent trisomies, deletions, and t(1;4) translocations were observed. Negative results for EBV nuclear antigen indicate that this cell line is an EBV-negative cell line.
Antigens, Differentiation, B-Lymphocyte↗
Monoclonal rat anti-human lymphocyte antibody Campath-1 binds to T and B lymphocytes but effectively lyses only T cells.
Binding and human complement-mediated T and B lymphocyte lysis were investigated in bone marrow samples obtained from 15 normal donors and 12 patients with a variety of malignant disorders undergoing marrow cryopreservation prior to autologous bone marrow transplantation. All marrow samples were obtained during remission except for one patient with neuroblastoma. The mononuclear cell fractions were collected and the distribution of B cell restricted markers (surface Ig and GP-70) and T cell surface markers (Leu-1 and rosettes with sheep red blood cells) were studied before and after marrow purging with Campath-1, a monoclonal rat anti-human lymphocyte antibody, and autologous serum as complement. Effective lysis of T lymphocytes (greater than 99.5%) was documented in all cases. However, although effective binding of Campath-1 to B lymphocytes was uniform, no effective lysis occurred. The data suggest that effective lysis of mature T lymphocytes can be accomplished while leaving normal B lymphocytes intact.
Antibodies, Monoclonal↗
Phorbol esters and hairy cell leukemia: effects on cell morphology and surface membrane features and comparison with other B cell leukemias.
Hairy cell leukemia (HCL) mononuclear cells were incubated with the phorbol ester TPA in an attempt to induce further maturation and were compared with B cell chronic lymphocytic leukemia, prolymphocytic leukemia, and non-Hodgkin's lymphoma cells. Morphology, surface features, membrane markers, tartrate-resistant acid phosphatase, and Ig secretion were examined. HCL cells spread and adhered firmly after TPA, producing elongated filopodia. Cells still retained ribosomal lamellar complexes, and increased numbers of dense bodies were seen. TPA enhanced the adherent and phagocytic properties of HCL cells, producing a modest increase in the expression of membrane Ig, GP-70, and Leu-M5 markers, tartrate-resistant acid phosphatase, and Ig secretion. Other neoplastic B cells behaved differently, forming readily detachable clumps without elongated filopodia. Maturation to plasma cells and hairy cell features were readily evident in all cases. These differences in growth patterns were consistent and may be used to distinguish HCL from other B cell neoplasias.
Acid Phosphatase↗
Phorbol ester induction of plasmacytoid and hairy cell leukemia features in B-type lymphocytic leukemias: the relation to B-cell differentiation and maturation.
Mononuclear cells concentrated from 11 patients with chronic lymphocytic leukemia (CLL), 7 with non-Hodgkin's lymphoma in leukemic phase (NHL), 5 with hairy cell leukemia (HCL), 1 with prolymphocytic leukemia (PLL), and 1 with plasma cell leukemia (PCL) were induced to differentiate with various doses of TPA. The degree of induction was followed for up to 6 days by measuring the expression of surface membrane markers (SmIg and GP-70) and Ig secretion, the induction of tartrate-resistant acid phosphatase (TRAP) and by recording ultrastructural changes as seen by electronmicroscopy. The results show a dose and time dependency of the TPA effect and a great heterogeneity in the cellular response, particularly in cells obtained from B-CLL patients. TPA induced two main features, namely the development of "plasmacytoid" or "hairy cell" leukemia features that clearly depended on the dose and duration of treatment with the phorbol ester. The plasmacytoid features were more frequently encountered with lower doses (1 ng/ml) of TPA and were more evident after shorter exposures to TPA (1-2 days). Nevertheless, the hairy cell features were more striking after incubation with higher concentrations of TPA (10-100 ng/ml) after longer periods of incubation (up to 6 days) with lower doses of TPA. The various features of differentiation measured including cell morphology, surface membrane markers, Ig secretion, and TRAP staining, were frequently independent of each other, suggesting an autonomous pathway of differentiation for some of these features. Furthermore, in most of the cases, hairy cell leukemia features were obtained more frequently following TPA exposure than plasmacytic changes.
Acid Phosphatase↗
Heterogeneity in TPA-induced differentiation of B-chronic lymphocytic leukemia cells: development of hairy cell or plasmacytoid features are time and dose dependent.
Cells from 11 chronic lymphocytic leukemic (CLL) patients were induced to differentiate with various doses of tetradecanoyl phorbol-13-acetate (TPA) and the degree of induction was followed up to six days by measuring the expression of two surface membrane markers (SmIg and GP-70), Ig secretion, tartrate-resistant acid phosphatase (TRAP), and ultrastructural changes. The results indicate dose and time dependency of the TPA effect and a great heterogeneity in the response to TPA among cells from different CLL patients. Furthermore, the two main TPA-induced features, the "plasmacytoid" or "hairy cell" features depended on the dose and duration of treatment with the phorbolester. The plasmacytoid features were more frequently encountered at low doses (1 ng/ml) of TPA and were evident after short exposures to TPA (1-2 days). The hairy cell features were more obvious after incubation with higher doses of TPA (10-100 ng/ml) or at Day 6 with lower doses of TPA. The differentiation features measured, including cell morphology, surface membrane markers, Ig secretion, and TRAP staining, appeared to be independent of each other suggesting an autonomous pathway of differentiation for some of these features.
Acid Phosphatase↗
Expression of the mid-stage differentiation B-cell antigen GP-70 in patients with early and stable form of B-CLL.
The expression of B-cell surface markers SmIg and GP-70 was determined on the mononuclear cells from the peripheral blood of 25 patients with chronic lymphocytic leukemia (CLL), 10 patients with multiple myeloma (MM), 6 normal blood donors and in 3 cases of unexplained persistent lymphocytosis. GP-70 was expressed only in CLL patients whereas multiple myeloma patients, blood donors and patients with unexplained lymphocytosis were all negative to GP-70. SmIg was expressed in CLL patients and in some of the multiple myeloma patients. Subgrouping of CLL patients to "early", stable patients (10) and to more advanced CLL patients (15) revealed differential expression of GP-70 on CLL cells from patients with more advanced stage of disease rather than in the patients with the "early" stable clinical course of disease. SmIg, on the other hand, was expressed equally on both subgroups of CLL. Furthermore, in some cases (25%) where SmIg and the light chains of Ig were only weakly expressed or were absent, GP-70 was markedly expressed. These findings suggest that GP-70 can be used as a single laboratory determination to establish clonality of the B-lymphocyte proliferation in CLL. In addition, expression of GP-70 correlates with significant clinical parameters of the disease.
Aged↗
Characterization of a novel Burkitt's lymphoma-associated antigen: GP70. Reactivity of anti-GP70 antibodies with various malignant and non-malignant cell lines.
A glycoprotein of 70 kDa (GP70) was isolated from sera of Burkitt's lymphoma (BL) patients and used to immunize rabbits. Anti-GP70 antibodies at a high titer were obtained and used for screening of cancer cells of various origin by the indirect immunofluorescence test. Thus, 66% of BL-cell lines tested were positive to GP70. On the other hand, all lymphoblastoid cell lines tested were negative. Moreover, all peripheral blood cells and mononuclear cells from tonsils were negative, indicating specificity of antibodies to malignant transformation. Comparison between positively stained BL-cell lines indicated no correlation between the presence of GP70 and EBNA. Positive stain (1-5%) obtained with bone marrow cells might indicate that anti-GP70 antibodies are directed against a surface membrane differentiation glycoprotein.
Antibodies, Neoplasm↗
Generation of a monoclonal anti-GP70 antibody and characterization of its reactivity with various human cell lines and cells from leukemia-lymphoma patients.
Monoclonal anti GP-70 antibodies (BI) were generated in mice and used for screening of various malignant and non-malignant cell lines. The reactivity of these monoclonal antibodies was compared with that obtained with the polyclonal anti GP-70 antibody described in earlier studies [1-3]. The results indicated complete similarity in reactivity of both of the antibodies used. Furthermore, the reactivity of BI antibodies with cell samples obtained from a variety of leukemia and lymphoma patients and with peripheral blood samples from healthy blood donors was also very similar to the pattern of specificity described in earlier reports for the polyclonal preparation. From these studies we conclude that the monoclonal antibodies can substitute the polyclonal anti GP-70 antibodies in the diagnosis and subtyping of B-type leukemias and lymphomas.
Antibodies, Monoclonal↗
Hairy cell leukaemia: effects of phorbol ester on cell morphology and adherence and comparison with other B-cell neoplasias.
This report documents phorbol ester-induced changes in cell morphology in 9 patients with hairy cell leukaemia (HCL) and contrasts them with those obtained in cells from 20 patients with B-type chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma in leukaemic phase (NHL). The phorbol ester caused hairy cells to adhere strongly and produce thin elongated cytoplasmic extensions. Other cells showed marked surface ruffling, and contained increased numbers of phagolysosomes, although cells still retained ribosomal lamellar complexes. This in vitro growth pattern differed from that observed in B-CLL and NHL cells, which readily detached in clumps with minimal adherence. CLL and NHL-cells did not show macrophage features but developed plasmacytoid and hairy cell-like features. It is suggested that these different growth patterns may aid in distinguishing HCL from other B-cell neoplasias.
B-Lymphocytes↗
Phorbol ester (TPA)-induced surface membrane alterations in B-type hairy cell and lymphocytic leukemia cells.
This report documents phorbol ester (TPA)-induced changes in cell morphology, and in vitro growth patterns in 9 patients with hairy cell leukemia (HCL), 21 with B-type CLL and non-Hodgkin's lymphoma in leukemic phase (NHL), and 10 with acute non lymphoblastic leukemia (ANLL). TPA caused cells from HCL to adhere strongly and produce elongated cytoplasmic extensions. Many of these cells had an appearance resembling fibroblasts, while others showed marked surface ruffling and spreading containing increased dense bodies, and phagolysosomal vacuoles as seen by transmission electron microscopy. This HCL in vitro growth pattern after TPA exposure differed from that seen in B-CLL and NHL cells, which only adhered moderately after 72 hours and readily detached in clumps. CLL and NHL-cells did not show ultrastructural features of macrophages but had either plasmacytic or HCL features. It is suggested that these different growth patterns may aid in distinguishing HCL from other B-cell neoplasias. The expression of surface markers, tartrate resistant acid phosphatase (TRAP) and Ig secretion were studied in some B-CLL, NHL and HCL cells after exposure to different concentrations of TPA for up to 6 days. Results showed that the documented changes were frequently both dose and time dependent and the most striking HCL-features were encountered after 6 days incubation with higher concentrations of TPA. However, individual variation from case to case was noted. Nevertheless, it seems that TPA induces neoplastic B-cells to mature into secreting plasmacytoid lymphocytes, and cells with features of HCL with variable expression of surface markers and TRAP.
Acute Disease↗
Development of a novel C1q immunoadsorbent for removal of circulating immunecomplexes: quantitative isolation of hepatitis B virus surface antigen and immunecomplexes.
A technique for large scale production of human C1q from plasma by affinity chromatography on an anti-C1q column is described. Affinity purified C1q was covalently coupled to a newly developed agarose polyacrolein microsphere beads immunoadsorbent. This immunoadsorbent was utilized for quantitative removal of artificially formed bovine serum albumin (BSA)-anti-BSA immune complexes (IC). The C1q affinity column was then used for the isolation of immunecomplexes containing hepatitis B virus (HBV) surface antigen (HBsAg) from serum of an HBsAg carrier. Identical columns may be utilized for quantitative removal of a variety of IC from blood of patients with infectious and autoimmune diseases, as well as neoplastic diseases. Furthermore, dissociated immunecomplexes will provide an additional source for purification of specific antigens.
Animals↗
Subgroup analysis of BL-cell lines with polyclonal BL-specific antibodies.
A Burkitt's lymphoma (BL)-specific antibody (anti-GP70), previously described, was used to analyse 22 different BL-cell lines. The results indicated specificity of antibodies to lines that contain both surface membrane Ig (SmIg) and cytoplasmic Ig (CyIg). BL-cell lines derived from more immature B cells that do not have SmIg but rather have only CyIg were negative. A comparative study with antibody to common ALL antigen (CALLA) and to another BL-specific antigen (BLA) revealed coexpression of GP70 with those two antigens, but no identity between them.
Animals↗