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Biomedical subjects

J Gordon

Publications and source records attributed to J Gordon.

At least 397 records · Page 22Linked to original sources
PubMed1983

Immunization with idiotypic immunoglobulin protects against development of B lymphocytic leukemia, but emerging tumor cells can evade antibody attack by modulation.

Immunization of strain 2 guinea pigs with idiotypic IgM obtained from serum of animals in the terminal phase of the L2C leukemia produced high levels of circulating anti-idiotypic antibody that was cytotoxic for the tumor cells in the presence of syngeneic C. Such animals showed good protection against injected tumor cells, but after a long delay, leukemia did develop. As tumor cells appeared in the blood, anti-idiotype was consumed, but the cells displayed little or no surface Ig and could not be killed in vitro by anti-idiotype and C. However, as serum antibody levels fell, the cells displayed increasing amounts of surface IgM lambda of the same idiotype and regained their susceptibility to the antibody and C in vitro. It appears, therefore, that the ability of tumor cells to modulate their target idiotype can present a considerable problem for antibody-mediated attack.

Animals↗
PubMed1983

Phenotypes in chronic B-lymphocytic leukemia probed by monoclonal antibodies and immunoglobulin secretion studies: identification of stages of maturation arrest and the relation to clinical findings.

Neoplastic populations from 25 cases of B-lymphocytic leukemia (B-LL) were investigated in an attempt to define the stages of maturation arrest represented in this disease and the relationship, if any, to various clinical parameters. Intrinsic to this study was the expression of a number of B-cell antigens defined by monoclonal antibodies. These included antibodies to B1 and B2, both expressed exclusively on B lymphocytes, but with the latter probably restricted to a narrow window of differentiation, BB-1 and LB-1, both markers of activated lymphocytes, and 38.13, a monoclonal antibody raised against and recognizing an epitope expressed on Burkitt lymphoma cells. While the patterns of reactivities were complex, the cases could be classified into various groups on the basis of the phenotypes revealed. These were termed "pre-B," "early-B," "intermediate-B," "mature-B," and "secretory-B" from their patterns of immunoglobulin (Ig) isotype expression and their capacity to secrete Ig in short-term culture. Although B1 was detected on neoplastic cells from all but one case, its intensity of expression varied markedly, being strongest on the "mature-B" and "secretory-B" cases and weakest on the "pre-B" type. The expression of B2 was essentially restricted to the "intermediate-B," "mature-B," and "secretory-B" cases and was usually, but not invariably, accompanied by the coexpression of surface IgM and IgD. While expression of BB-1 was restricted to a few cases with mature features, LB-1 was more frequently detected and found predominantly on "intermediate-B" and "mature-B" cases. The 38.13 antibody was found to react weakly with a number of the populations coexpressing IgM and IgD. The export of large amounts of whole Ig was restricted to three "secretory-B" cases all of which were associated with a serum M-component corresponding to the Ig isotype secreted in vitro. In contrast, the secretion of free Ig light chains was a consistent feature of all B-LL, and the amounts detected did not vary considerably between the different types. No correlation between immunologic cell-type and the stage of the disease was apparent. Classification of the cases into "true" B-chronic lymphocytic leukemia and immunocytoma similarly revealed no strict association of these histopathologic entities with any particular phenotypic group, although those cases with the more mature features tended to be immunocytomas. The findings are discussed within the context of normal B-cell differentiation pathways.

Antibodies, Monoclonal↗
PubMed1982

Monoclonal antibodies against eucaryotic ribosomes. Use to characterize a ribosomal protein not previously identified and antigenically related to the acidic phosphoproteins P1/P2.

Mice were immunized against chick ribosomes with the use of various protocols and immunogen preparations. Hybridomas were prepared, clones screened, and specific antibodies identified by reversible protein staining followed by immunoperoxidase staining on nitrocellulose blots. Clones were obtained which secreted specific antibodies against ribosomal proteins S6, L7, L18a, P1/P2, and also against ribosomal RNA. Antibodies were typed by means of a dot-binding assay with typing antibodies immobilized on a solid support of nitrocellulose, and also characterized by their species cross-reactivities. The common determinant on proteins P1 and P2 cross-reacted with proteins of similar molecular weight in all eucaryotes tested, and with a determinant in a previously uncharacterized 38,000-dalton protein of the large ribosomal subunit. We designate this protein P0. The determinant of P0 was also present in a protein of similar molecular weight in all eucaryotes tested. Unlike P1 and P2, P0 was not removable from ribosomes by an ethanol-NH4Cl washing procedure. No evidence for a precursor-product relationship between P0 and P1/P2 was found. P0, P1, and P2 were found in active polysomes and in the nucleolus. The molecular weights of the nucleolar forms were not identical with those of the cytoplasmic forms, suggesting some processing during ribosomal assembly and/or transport.

Animals↗
PubMed1982

The phosphorylation of ribosomal protein S6 in rat tissues following cycloheximide injection, in diabetes, and after denervation of diaphragm. A simple immunological determination of the extent of S6 phosphorylation on protein blots.

The extent of phosphorylation of S6 was measured in a variety of cells, organs, and tissues using a simplified procedure. Ribosomal proteins were separated by electrophoresis on a one-dimensional urea-sodium dodecyl sulfate gel. They were transferred electrophoretically to nitrocellulose, and S6 was specifically stained by means of its reaction with a monoclonal antibody. The mobility of the stained protein was shown to be a measure of the extent of its phosphorylation. Using this method, we found that cycloheximide injection of rats gives rise to the phosphorylation of S6 in a variety of organs and tissues: diaphragm, heart and skeletal muscle liver and kidney, but not brain. Diabetes induced with alloxan did not result in the phosphorylation of S6 in any of the tissues examined, and subsequent insulin injection resulted in a slight increase in the phosphorylation of S6 in liver. Insulin injection in normal rats also caused the phosphorylation of liver S6. Unilateral denervation of rat diaphragm resulted in phosphorylation of S6 in the denervated portion but not in the innervated portion of the diaphragm.

Animals↗
PubMed1982

Significance of a (4;11) translocation in acute lymphoblastic leukemia.

This report describes a case of null cell congenital acute lymphoblastic leukemia associated with a (4;11) translocation. This chromosome abnormality is associated with acute lymphoblastic leukemia and probably more specifically with congenital acute lymphoblastic leukemia. A review of the literature is presented.

Chromosomes, Human, 4-5↗
PubMed1982

The retina of the newborn human infant.

We have examined a pair of eyes from a normal, full-term infant who died at 8 days as a result of accidental injury. Eyes were obtained immediately after death, fixed, and sectioned for light microscopy. Results from both eyes were substantially the same. The macular region was still drastically immature at 1 week. Even though a foveal depression existed, all cell layers were still present across it. Furthermore, the inner nuclear layer was divided into two separate layers. The receptor layer was reduced to one or two cells thick; receptors had both inner and outer segments, but they were very short and stumpy. The region of immaturity covered about 5 degrees of the retina. These findings suggest that the central region of a human infant's retina is probably not fully functional at birth.

Humans↗
PubMed1982

Anti-tumor immunity in B-lymphocyte-deprived mice. III. Immunity to primary Moloney sarcoma virus-induced tumors.

Tumor induction and immunity to tumors were studied following the injection of Moloney sarcoma virus (MSV) into mice whose B-lymphocyte functions had been suppressed by the chronic administration of anti-IgM antibodies. Two preparations of MSV were used; one which gives rise to tumors which uniformly regress in normal adult mice, and another which elicits progressively growing tumors in the majority of recipients. The tumor incidence, mean tumor size, and tempo of regression were not modified by treatment with anti-IgM. However, whereas tumors induced by the regressor virus were all rejected in 19 NRG-treated and 29 untreated recipients, continued growth was obtained in 2 of 23 B-lymphocyte-deprived mice. Furthermore, in 9 additional mice from this group, apparent rejection was followed by tumor recurrence at the site of the initial tumor. Continued growth was accompanied by widespread metastasis. These tumors were freely transplantable to normal syngeneic recipients. Metastasis and transplantability were also detected in 7 of 24 anti-IgM-treated mice given progressor virus, but were not seen in the control animals. Recurrence and metastasis was obtained despite the presence of high levels of specific cytotoxic T lymphocytes in the spleen. It is concluded that B lymphocytes or their products play an essential role in host protection against MSV-induced tumors.

Animals↗
PubMed1982

Ribosomal protein S6 from Xenopus laevis ovaries. Isolation, phosphorylation in vivo and cross-reaction with heterologous anti-S6 antibodies.

Ribosomal protein S6 from Xenopus laevis ovaries was prepared by ion-exchange chromatography on phosphocellulose and gel filtration on Sephadex G-75. The protein was identified as S6 from its position on two-dimensional polyacrylamide gels and from its immunological cross-reaction with monoclonal antibody raised against chicken liver S6, and from the fact that it is the major phosphorylated protein of the small subunit. When oocytes were incubated with [32P]orthophosphate in the presence of progesterone, 32P incorporation of 40-S ribosomal proteins was stimulated about 10-fold over controls without hormone. The bulk of the 32P radioactivity was incorporated into protein S6.

Animals↗
PubMed1982

Natural resistance mechanisms may play a role in protection against chemical carcinogenesis.

Mice deprived of B lymphocytes by the chronic administration of anti-IgM antibodies have been shown to possess a heightened natural resistance (NR) to micro-organisms, to parental bone marrow, and to natural killer (NK)-sensitive tumors in vitro and in vivo. Experiments described in this communication indicate that the latent period of primary tumors induced by the injection of methylcholanthrene (MC) is also prolonged in these mice. This observation suggests that NR mechanisms may provide protection against primary chemically induced tumors.

Animals↗
PubMed1982

Correlation between Ig-synthesis patterns and lymphoma classification.

This study examines the link between free immunoglobulin (Ig) light-chain (LC) secretion and the developmental stage of the neoplastic B-cell of origin in B-cell lymphomas. The Kiel developmental scheme for lymphoma classification has been used to define the tumour-cell populations. Twenty-four B-cell lymphomas have been studied. In the small-lymphocytic lymphoma group, secreted Ig consisted of LC exclusively or in excess over heavy-chain (HC). Lymphomas of follicular-centre-cell origin, considered to be from cells further along the normal B-cell differentiation pathway, can be divided into centroblasts or centrocytes according to their histological appearance in tissue sections. Centroblastic lymphomas exhibited strong surface IgM or IgG expression, and the secretion of whole Ig was higher than by cells from the small-lymphocytic lymphomas. Synthesis of HC and LC was balanced in these cultures, both intracellularly and in secreted material. The centrocytic lymphomas comprised a functionally more heterogeneous group, the SIg varied in intensity and was of surface IgM, D or G. Likewise Ig synthesis was variable in quantity and composition, some cases secreting LC exclusively while others, including the cases expressing SIgG, secreted balanced HC and LC. In the Kiel classification centrocytes are considered to be more mature than centroblasts. Our data suggest that centrocytic lymphomas are heterogeneous in origin, some preceding and others following centroblasts in the B-cell maturation sequence. These data are discussed in relation to current concepts of B-cell maturation and lymphoma histology.

B-Lymphocytes↗
PubMed1982

The influence of antigen density and a comparison of IgG and IgM antibodies in the anti-complementary modulation of lymphocytic surface immunoglobulin.

Experiments were carried out to determine the influence of antigen density on anti-complementary modulation, defined here as the conferring by anti-immunoglobulin (Ig) of resistance to lysis of guinea pig L2C leukaemic cells varied widely in their quantitative expression of surface membrane Ig as judged by the binding to cells of 125I-labelled Fab' fragments from anti-Ig, and a good correlation between the bulk antigen density and the percentage of cells lysed by anti-Ig plus C was obtained (P=0.02). In the presence of 10 mM sodium azide, which has been shown to diminish the modulation occurring during simultaneous incubations with anti-Ig and C, this correlation was even stronger (P less than 0.001). No zone could be defined in which the level of surface Ig expression was sufficient to serve complement lysis but too low for modulation. Furthermore, both the degrees and rates of modulation occurring on incubation with antibody at 37 degrees C, either before C addition or in the presence of lytic C, were similar for populations of high, low, or intermediate antigen density. Separation of cells by their size or density failed to yield populations differing in either their susceptibility to humoral killing through anti-Ig or their modulating capacity. IgG and IgM antibodies to the L2C cell surface Ig evoked similar levels of killing with syngeneic C, and when compared for their ability to promote anti-complementary modulation, no difference was revealed in either the rate or degree of modulation occurring during incubations at 37 degrees C with the two isotopes. The findings are discussed with particular reference to observations on the modulation of mouse thymus leukaemia (TL) antigens.

Animals↗
PubMed1982

Lymphocyte function in anergic patients.

The lymphocyte function of anergic surgical patients who are at increased risk for sepsis and mortality was studied. In vitro lymphocyte responses appear to be normal in most instances, in that over 80% of patients showed a normal response in a standardized mixed leucocyte culture reaction. Similarly, 56% of the lymphocytes from anergic patients showed a positive in vitro proliferative response with PPD. The ability of in vitro-activated lymphocytes to elicit a skin reaction was determined by culturing the cells of anergic patients with PPD and then reinjecting the lymphocytes or their supernatants intradermally into the original donor. When there was a positive proliferative response to PPD in vitro, the reinjected cells or supernatant elicited a positive skin reaction in 79% of the anergic patients. In contrast, a skin reaction was obtained in less than 20% of the instances when there was no in vitro proliferation to PPD or when the cells were cultured without antigen. These results suggest that one of the acquired immune defects in these anergic patients is an in vivo block of lymphocyte activation.

Cells, Cultured↗
PubMed1982

Loss of surface-bound antibody accompanying the anti-complementary modulation of leukemic B cell immunoglobulin: contrasting effects of antibodies directed against idiotypic and constant regions.

Guinea pig L2C leukemic lymphocytes display at their surfaces monoclonal IgM, which when compared with antibody undergoes rapid redistribution and variable endocytosis. One consequence of this is that the cells can prove resistant to lysis by complement subsequently added to the system, a process termed here anti-complementary modulation. We studied quantitatively the extent of antibody loss accompanying the modulation by radioimmunolabeling the cell surfaces with 125I-Fab' gamma fragments from an anti-antibody. Antibody directed against the constant region of the IgG light chain (anti-lambda) gave modulation effective against syngeneic (guinea pig strain 2) complement that closely paralleled the disappearance of anti-lambda from the cell surfaces. Antibody directed against the idiotypic region of the light chain (anti-Id) was as effective as anti-lambda in modulating against syngeneic complement. However, the bulk of the anti-Id was seen by radioimmunolabeling to persist on the surfaces of the resistant cells, even after prolonged exposure at 37 degrees C, and was shown by immunofluorescence to be in a patched configuration. In contrast to the results with syngeneic complement, modulation effective against rabbit complement appeared to have an absolute requirement for clearing of the antibody: thus anti-lambda could modulate, anti-Id could not. The differences observed between anti-lambda and anti-Id could not be accounted for by differences in their isotypic (Ig subclass) composition nor by the numbers of antibody molecules bound. Studies with directly fluoresceinated and 125I-labeled anti-lambda revealed endocytosis rather than shedding was the major route of antibody loss from the cell surfaces over the period of anti-complementary modulation. The findings are discussed in relation to mechanisms that enable leukemic B lymphocytes to escape destruction when confronted by antibody and complement.

Animals↗