Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel immunocytochemical approach to the detection of cytoplasmic antigens, exemplified by immunoglobulin and CD3, was evaluated using benign and 155 malignant lymphohematopoietic cell specimens and conventional techniques for detailed comparison. It relies on (a) electrostatic cell attachment to poly-L-lysine-coated multispot slides, (b) sequential use of glutaraldehyde fixation and detergent permeabilization, and (c) staining of endogenous peroxidases and antigens in contrasting colors. Differential staining instead of inactivation of endogenous peroxidases and avoidance of artifacts incurred in conventional cytocentrifugation, dehydration, and alcohol or acetone fixation uniquely afforded improved precision in cell identification, clear distinction of cytoplasmic from surface antigenic staining, and greatly enhanced sensitivity in antigen detection, all combined with increased performance efficiency achieved by the use of multispot slides. With this method, cytoplasmic immunoglobulin and CD3 were found more widely distributed than has been previously recognized. Thus, almost all malignant cells in all cases of B-cell lymphoma/leukemia (encompassing the major subtypes) and T-ALL, as well as substantial proportions of benign mature B- and T-lymphocytes, stained strongly positive for cIg and cCD3, respectively, whereas myeloid cells were consistently negative. High sensitivity combined with excellent cytomorphology and differential myeloperoxidase staining permitted unequivocal differentiation of minute fractions of malignant cells against a heterogeneous background of benign cells.
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PMID:Optimized detection of cytoplasmic immunoglobulin and CD3 in benign and malignant lymphoid cells: enhanced sensitivity combined with differential staining of endogenous peroxidases and light microscopic morphology. 768 87

A natural N-linked glycosylation site (Asn-Val-Thr) at amino acid positions 18-20 (Kabat's numbering) was identified in the framework-1 (FR-1) region of the light chain variable (V kappa) domain of a murine anti-B cell lymphoma Ab, LL-2. Our earlier studies demonstrated that no contact between the V kappa-appended oligosaccharide and the Ag binding site was evident, because glycosylation at this site did not affect the Ag binding property of the Ab. By using the murine LL-2 F(ab')2 fragment (which is devoid of constant region-appended oligosaccharide) as substrate, as much as five bifunctional chelator molecules per F(ab')2 fragment could be site specifically conjugated at the V kappa-appended carbohydrate moiety with no reduction in immunoreactivity. The resulting conjugates labeled efficiently with both 90Y and 111In, with no significant effect on Ab affinity. In contrast, conjugation of less than five chelates/Ab fragment randomly at lysine residues resulted in a three- to fivefold reduction in affinity. By a single Arg to Asn mutation, an N-linked glycosylation site similar to that of LL-2 was introduced in the FR-1 segment of a nonglycosylated, humanized anti-carcinoembryonic Ag (CEA) Ab, MN-14 (hMN-14). Glycosylation at the engineered carbohydrate-addition site was demonstrated by SDS-PAGE analysis. Neither glycosylation nor site-specific conjugation of chelate at the V kappa-appended carbohydrate moiety resulted in the loss of immunoreactivity. The glycosylated hMN-14 conjugate labeled efficiently with 90Y.
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PMID:Engineering a unique glycosylation site for site-specific conjugation of haptens to antibody fragments. 775 35

Human mononuclear leukocytes (MNL), probably OKT4-positive T cells, produced an eosinophil chemotactic factor (ECF) when they were cocultured with irradiated BALL-1, a B cell lymphoma line. Treatment of MNL, with anti-IL-2 antibody failed to suppress BALL-1-induced ECF production. Periodate-lysine-paraformaldehyde-fixed but not acetone- and ethanol-fixed BCLL induced evident ECF production. These results suggested that some cell surface molecules play a role in the induction of ECF production. Isoelectric point of BALL-1-induced ECF was around pH7, whereas that of IL-2-induced ECF was around pH 5. The molecular weight of BALL-1-induced ECF was between 10 and 30 kD. Although a combination of MoAb against IL-3, IL-5, and GM, CSF suppressed the activity of IL-2-induced ECF, it failed to suppress that of BALL-1-induced ECF. Furthermore, BALL-1-induced ECF suppressed fMLP-induced respiratory bursts of eosinophils, while IL-2-induced ECF failed. We propose that at least one reason for eosinophil infiltrate into the stroma of tumors is that the tumor cells stimulate T cells to produce BALL-1-induced ECF, and the eosinophils attracted by the ECF exhibit different functions from those by other ECF.
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PMID:A B cell lymphoma line, BALL-1 stimulates T cells to produce a unique eosinophil chemotactic factor. 815 10

Biopsy specimens obtained from 2 patients with monocytoid B cell lymphoma, 7 with mantle zone lymphoma, 7 with small lymphocytic lymphoma or B chronic lymphocytic leukemia, and 6 with hairy cell leukemia were investigated using an immunohistochemical method to detect their immunophenotypic characteristics. Periodate-lysine-paraformaldehyde-fixed frozen biopsies from the lymph node, peripheral blood, bone marrow, spleen, tonsil, lung, and stomach were studied. Monocytoid B cell lymphoma exhibited the immunophenotype of surface(s) IgD-/DRC-1-/Leu-1(CD5)-/Leu-M5(CD11c)-, +/- on the neoplastic cells or neoplastic lesions, mantle zone lymphoma exhibited that of sIgD+/DRC-1++/Leu-1-,+/Leu-M5-, small lymphocytic lymphoma or B chronic lymphocytic leukemia that of Leu-1+/sIgD-,+sIgD-,+/DRC-1- > +Leu-M5-, and hairy cell leukemia that of Leu-M5++/sIgD- >> +/Leu-1- >> +/DRC-1-. We therefore suggest that these four types of lymphomas can be differentiated by a combination of anti-sIgD, DRC-1, Leu-1, and Leu-M5 monoclonal antibodies based on their immunophenotypic characteristics.
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PMID:Immunohistochemical characteristics of monocytoid B cell lymphoma, mantle zone lymphoma, small lymphocytic lymphoma (or B chronic lymphocytic leukemia), and hairy cell leukemia. 806 18

Production of an eosinophil chemotactic factor (ECF) from human mononuclear leukocytes (MNL) was induced by coculture with an irradiated B cell lymphoma line, BALL-1. BALL-1 induced ECF production from OKT4-positive T lymphocytes without evident IL-2 production. Treatment of MNL with anti-IL-2 antibody failed to suppress the BALL-1-induced ECF production, whereas the treatment strongly inhibited IL-2-induced ECF production. Control supernatants of BALL-1 cells alone did not induce ECF production. BALL-1 fixed with periodate-lysine-paraformaldehyde, but not acetone or ethanol, induced evident ECF production. The isoelectric point of BALL-1-induced ECF (m.w. 10-30 kD) was around pI 7, whereas that of the IL-2-induced ECF was around pI 5. A combination of monoclonal antibodies against IL-3, IL-5, and GM-CSF suppressed the activity of the IL-2-induced ECF but not that of the BALL-1-induced ECF. BALL-1-induced ECF suppressed a respiratory burst from an eosinophilic cell line (YY-1) induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine, whereas the IL-2-induced ECF did not, suggesting that the biological function of these two ECF is different, at least in the effect on respiratory burst of eosinophils. From the present results we propose that one reason for infiltration of eosinophils into the stroma of tumors is that some tumor cells can stimulate OKT4-positive T lymphocytes to produce an ECF, and that eosinophils attracted by this ECF exhibit biological functions which are different from those of eosinophils attracted by other ECF.
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PMID:Induction of an eosinophil chemotactic factor production from T lymphocytes by a B cell lymphoma line. 837 May 99

We have produced immunotoxins using LL2, a monoclonal antibody which binds to human B-cell lymphomas and which, in a radioiodinated form, induced responses in lymphoma patients (D.M. Goldberg et al., J. Clin. Oncol., 9: 548-564, 1991). We have coupled LL2 to Lys-PE38KDEL, a derivative of Pseudomonas exotoxin (PE) which does not bind to the PE receptor. LL2-PE38KDEL was cytotoxic toward several Burkitt's lymphoma lines, with 50% inhibitory concentration values ranging from 2 to 6 ng/ml (10-30 pM). Another immunotoxin, LL2-Fab'-PE38KDEL, was produced by chemically coupling the Fab' fragment of LL2 to Lys-PE38KDEL. LL2-Fab'-PE38KDEL also was cytotoxic toward the Burkitt's cells, with a 50% inhibitory concentration of 1-2 ng/ml (13-24 PM). The antibody LL2 alone had no cytotoxicity toward the malignant cells, and excess LL2 prevented the cytotoxicity of LL2-PE38KDEL and LL2-Fab'-PE38KDEL. Control immunotoxins UPC-10-PE38KDEL and Mu-9-Fab'-PE38KDEL were not cytotoxic. LL2-PE38KDEL and LL2-Fab'-PE38KDEL bound to cells with 50% and 17% of the affinity of LL2, respectively. Both immunotoxins, but not UPC-10-PE38KDEL, prevented the development of CA-46 tumors in nude mice. LL2-PE38KDEL and LL2-Fab'-PE38KDEL, but not the control immunotoxins, led to complete regressions of measurable s.c. CA-46 tumors in nude mice, when given at 50% and 35% of the 50% lethal dose, respectively. LL2 alone significantly retarded the growth of CA-46 tumors but did not cause complete tumor regressions. Immunotoxins containing derivatives of Pseudomonas exotoxin can be targeted to human B-cell lymphoma and merit further study as potential therapeutic agents.
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PMID:Pseudomonas exotoxin-based immunotoxins containing the antibody LL2 or LL2-Fab' induce regression of subcutaneous human B-cell lymphoma in mice. 842 63

The MHC class II molecule I-Ad has been reported to bind peptides containing a motif of six consecutive amino acids. We demonstrate that binding of the murine IgG2ab heavy chain allopeptide gamma 2ab 435-451 (Kabat numbering) to I-Ad is strongly enhanced by a novel first primary anchor (P1) three residues N-terminal to this hexamer. This is based on flow cytometric assessment of the I-Ad binding capacity of gamma 2ab peptide analogues, their antigenicity for I-Ad-restricted T cell clones and molecular modelling. The P1 pocket is broadly specific since allphatic, aromatic, acidic, the basic histidine and small polar side chains all allowed good binding. By contrast, asparagine, arginine and glycine reduced the binding capacity 10-, 16- and > 100-fold respectively. Truncation or glycine substitution at P1 decreased antigenicity by a factor > 1000. Nevertheless, I-Ad-restricted T cells are not completely dependent on this anchor since high concentrations of a peptide with glycine-substituted P1 elicited maximal responses. Additional anchoring side chains are found at P4, P6 and P9. The autologous IgG2aa heavy chain shares prominent epitopic residues with gamma 2ab 435-451 at P3, P5 and P8. However, the lysine of gamma 2aa at P9 impairs binding to I-Ad, which may explain why the gamma 2ab allopeptide-reactive T cells escaped negative selection. The data rationalize our observation (Bartnes, K. and Hannestad, K. 1997. Eur. J. Immunol. 27:1124) that these T cells recognize a syngeneic B cell lymphoma, provided its presentation of intrinsic gamma 2aa is enhanced by surface IgG2aa ligation.
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PMID:A novel first primary anchor extends the MHC class II I-Ad binding motif to encompass nine amino acids. 926 16

Chronic infection of the gastroduodenal mucosae by the gram-negative spiral bacterium Helicobacter pylori is responsible for chronic active gastritis, peptic ulcers, and gastric cancers such as adenocarcinoma and low-grade gastric B-cell lymphoma. The success of eradication by antibiotic therapy is being rapidly hampered by the increasing occurrence of antibiotic-resistant strains. An attractive alternative approach to combat this infection is represented by the therapeutic use of vaccines. In the present work, we have exploited the mouse model of persistent infection by mouse-adapted H. pylori strains that we have developed to assess the feasibility of the therapeutic use of vaccines against infection. We report that an otherwise chronic H. pylori infection in mice can be successfully eradicated by intragastric vaccination with H. pylori antigens such as recombinant VacA and CagA, which were administered together with a genetically detoxified mutant of the heat-labile enterotoxin of Escherichia coli (referred to as LTK63), in which the serine in position 63 was replaced by a lysine. Moreover, we show that therapeutic vaccination confers efficacious protection against reinfection. These results represent strong evidence of the feasibility of therapeutic use of VacA- or CagA-based vaccine formulations against H. pylori infection in an animal model and give substantial preclinical support to the application of this kind of approach in human clinical trials.
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PMID:Therapeutic intragastric vaccination against Helicobacter pylori in mice eradicates an otherwise chronic infection and confers protection against reinfection. 939 88

Chronic infection of the gastroduodenal mucosae by the gram-negative spiral bacterium Helicobacter pylori is responsible for chronic active gastritis, peptic ulcers, and gastric cancers such as adenocarcinoma and low-grade B-cell lymphoma. The success of eradication by antibiotic therapy is being rapidly hampered by the increasing occurrence of antibiotic-resistant strains. An attractive alternative approach to combat this infection is represented by the therapeutic use of vaccines. In the present work, we have exploited the mouse model of persistent infection by mouse-adapted H. pylori strains that we have developed to assess the feasibility of the therapeutic use of vaccines against infection. We report that an otherwise chronic H. pylori infection in mice can be successfully eradicated by intragastric vaccination with H. pylori antigens such as recombinant VacA and CagA, which were administered together with a genetically detoxified mutant of the heat-labile exterotoxin of Escherichia coli (referred to as LTK63), in which the serine in position 63 was replaced by a lysine. Moreover, we show that therapeutic vaccination confers efficacious protection against reinfection. These results represent strong evidence of the feasibility of therapeutic use of VacA- or CagA-based vaccine formulations against H. pylori infection in an animal model and give substantial preclinical support to the application of this kind of approach in human clinical trials.
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PMID:Eradication of chronic Helicobacter pylori infection by therapeutic vaccination. 977 98

90Yttrium-labeled monoclonal antibodies (mAbs) are likely to be important to radioimmunotherapy (RAIT) of a variety of cancers. The goal of this study was to select and evaluate a form of [90Y]mAb suitable for RAIT and determine conditions for high-yield, reproducible radiolabelings. 90Y-Labelings, at 2-40 mCi levels, of cdr-grafted versions of anti-B-cell lymphoma (hLL2) and anti-CEA (hIMMU-14) mAbs were optimized to >90% incorporations using the macrocyclic chelator DOTA as the metal carrier. In in vitro challenge assays, the stability of mAbs labeled with [90Y]DOTA was better than that of the corresponding [90Y]benzyl-DTPA conjugates. The retention of [90Y]DOTA-hLL2 on Raji tumor cells in vitro was similar to that of the same mAb labeled with [90Y]benzyl-DTPA and was about twice as much as with [125I]hLL2, indicating residualization of metalated mAb. Both [90Y]hLL2 conjugates, prepared using DOTA and Bz-DTPA, had similar maximum tolerated doses of 125 muCi in BALB/c mice and showed no discernible chelator-induced immune responses. Animal biodistribution studies in nude mice bearing Ramos human B-cell lymphoma xenografts revealed similar tumor and tissue uptake over a 10 day period, with the exception of bone uptake which was up to 50% lower for [88Y]DOTA-hLL2 compared to [88Y]Bz-DTPA-hLL2 at time points beyond 24 h. With [90Y]DOTA-hLL2 fragments, in vivo animal tumor dosimetries were inferior to those for the IgG, and kidney uptake was relatively high even with D-lysine administration. The ability of [111In]DOTA-hLL2 to accurately predict [90Y]DOTA-hLL2 biodistribution was established. These preclinical findings demonstrate that [90Y]DOTA-(CDR-grafted) mAbs are suitable for examination in clinical RAIT.
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PMID:90Yttrium-labeled complementarity-determining-region-grafted monoclonal antibodies for radioimmunotherapy: radiolabeling and animal biodistribution studies. 981 72


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