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J H Coggin

Publications and source records attributed to J H Coggin.

At least 37 records · Page 2Linked to original sources

Cross-reacting tumor associated transplantation antigen on primary 3-methylcholanthrene-induced BALB/c sarcomas.

Immunization of adult, syngeneic BALB/c mice with irradiated, primary MCA-induced sarcomas conferred reproducible, nonisologous TATA-associated cross-protection against challenge with other primary MCA sarcomas or in vitro passaged MCA sarcoma cells. Isologous, individually specific TSTA-associated protection was also detected. Irradiated, normal BALB/c spleen or muscle tissues were not similarly protective. Pronounced cross-protection was best detected with secondary cultured, in vitro adapted sarcoma challenge inoculum, which could be accurately standardized. These findings paralleled the good cross-protection reported previously with long-term cultured MCA-induced sarcoma cell lines. OFA was expressed as a TATA on all syngeneic, primary MCA-induced sarcomas tested by syngeneic adoptive transfer experiments and on MuLv-free MCA-induced, syngeneic Meth A sarcoma cells.

Animals↗

Human squamous cell carcinoma lines express oncofetal 44-kD polypeptide defined by monoclonal antibody to mouse fetus.

Most primary human carcinomas uniformly express an oncofetal epitope which has not been demonstrated previously in established human carcinoma cell lines. We successfully derived several low-passage cell lines of human squamous cell carcinoma (SCC) from head and neck tumors using an in vitro adaptation procedure, characterized these lines, and examined them for expression of a 44-kilodalton (kD) polypeptide (PP) oncofetal antigen (OFA) at the cell surface. Newly established an in vitro-passaged SCC cells retained characteristic microvilli, numerous desmosomes and tonofilaments, abundant rough endoplasmic reticulum, osmophilic keratohyaline granules, and other features of the primary SCC cells. These new cell lines and two long-term, established SCC lines (FaDu and Detroit 562) displayed OFA at the cell surface, as determined by flow cytometry using monoclonal antibody (MoAb) 115. While the FaDu and Detroit 562 lines exhibited aneuploidy during flow cytometric analysis, the new, low-passage SCC lines that we developed remained diploid as were the primary SCC cells from which they were derived. We propose that the expression of a 44-kD OFA is a common feature of human SCC. This marker may prove useful in the detection and treatment of these tumors.

Antibodies, Monoclonal↗

Radiation-induced lymphoblastic lymphomas/leukemias and sarcomas of mice express conserved, immunogenic 44-kilodalton oncofetal antigen.

X-ray-induced, lymphoblastic, T-cell lymphoma/leukemias from irradiated RF mice were observed to uniformly expressed a 44-kd oncofetal antigen (OFA). The OFA polypeptide was detected by flow cytometry, affinity column SDS-PAGE analysis, and immunoblotting with monoclonal antibody (MAb) 115 prepared against syngeneic mouse fetus. X-ray and ultraviolet (UV) induced murine fibrosarcoma cell lines, used as classic models in radiation biology, were also found to express the OFA, which suggested that the 44-kd OFA was a general transformation marker of tumors. Adult mouse thymocytes and other adult tissues expressed no OFA. The 44-kd polypeptide was located at the surface membrane of the tumors examined. In contrast to other reports, lymphoblastic lymphoma cell lines expressed the OFA as a cross-protective, rather than an individually-specific, tumor-associated transplantation antigen. Pronase treatment removed OFA from the surface of living lymphoma cells, whereas collagenase, neuraminidase, and hyaluronidase did not. The OFA was rapidly reexpressed upon culture of the pronase-treated cells. Taken together, these results suggest that the 44-kd OFA polypeptide described here may provide a useful cell surface marker for future radiation carcinogenesis studies. MAb 115 is a promising reagent for detecting tumor-associated 44-kd OFA, for assessing immunoregulatory perturbations to the OFA caused by radiation damage and for investigating the immunopathology of OFA-associated radiation damage.

Animals↗

Complete, circular papovavirus genomes in the cells of hamsters exposed to a horizontally transmitted lymphomagenic agent.

Contagious lymphomas were produced in a colony of Syrian golden hamsters by an unknown agent that also caused fatal ulcerative bowel disease (UBD) lesions prior to lymphoma development. A low percentage of these animals developed epitheliomas of the skin independently of the UBD or lymphomas. Previous work has shown that the epitheliomas contain numerous hamster papovavirus (HaPV) particles, whereas lymphomas do not. Cells from both kinds of tumors do contain HaPV DNA sequences, however. In this study, Southern blot hybridization showed that complete, circular HaPV genomes were present in these cells. Complete, circular HaPV genomes also were found in the cells of animals with UBD. Electron microscopy revealed the presence of HaPV particles in UBD lesions. These results, together with previous data, indicate that in the hamster, lymphomas contain complete, circular papovavirus genomes in the absence of virus particles, whereas epitheliomas and UBD lesions contain these genomes in the presence of virus particles.

Animals↗

The implications of embryonic gene expression in neoplasia.

The discovery that human as well as animal tumors generally expressed oncofetal antigens (OFAs) and that these antigens generate a variety of immune responses in the tumor-bearing host is of potential major significance in tumor biology. The concept of the reexpression of embryonic or fetal antigens (EAs) encoded by DNA, which is silent in adults but is essential in metazoan development, may mesh with the exciting concept of cancer causation. While this scenario is still only speculative, it provides an interesting forum for reviewing the current data concerning the role of OFAs in cancer processes. The literature describing OFAs and their embryonic counterparts, the EAs, in modern tumor and fetal immunobiology has become extensive and, unfortunately, is quite scattered. This article seeks to synthesize this complicated data base into a cogent presentation focusing on the immunological role of EAs and OFAs in fetal survival in utero and in tumor progression and regression, respectively. The immunogenicity and characteristics of the immune responses to EAs and OFAs will be presented and placed in perspective to the rapidly unraveling story of protooncogenes and oncogenes in tumor induction.

Animals↗

Mouse monoclonal antibody to embryonic antigen: development, cross-reactivity with rodent and human tumors, and preliminary polypeptide characterization.

Hybridomas producing IgM and IgG monoclonal antibodies (MoAb) to embryonic or fetal antigens (EA) were obtained in a completely syngeneic system. Lethally irradiated, 13-day-gestation, C57BL/6N mouse fetal cells or KCI extracts of these fetal cells obtained from primaparous donors were used as immunogens in several regimens to induce splenocytes in C57BL/6N mice that were utilized to form the hybridomas following fusion with a mouse myeloma line. Successful growth and cloning of the IgM-producing hybridomas required supplementation with factor(s) produced in the growth medium of the macrophage cell line RAW 264.7. An enzyme-linked immunosorbent assay (ELISA) was employed to screen the primary fusion hybridomas for antibody directed against fetal cell or adult cell determinants with the use of freshly explanted tissues. Glutaraldehyde-fixed fetal cells as well as crude fetal cell membranes were used as EA+ target cells (i.e., cell lines known to activate T-lymphocyte-mediated tumor resistance) in a solid-phase ELISA to perform quantitative ELISA adsorption tests of the MoAb. The anti-EA monoclonal IgM and the IgG detected common, embryo-specific antigen(s) on mouse, hamster, and human fetuses. Term fetal cells and adult normal tissues of the mouse, hamster, and human did not express cross-reactive determinants for the MoAb by absorption analysis and/or by direct binding in ELISA. EA expression as oncofetal antigens could also be detected with the monoclones on several rodent tumor cell lines tested as well as on a variety of human carcinomas but not on a spectrum of normal human tissues with the use of indirect ELISA absorption and affinity gel and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses. Fluorescence analysis with the monoclones demonstrated specific reactivity with the surface of EA+ tumor cells in the FACS IV flow cytometer. The responsible antigen was carried on a 44- and a 200-kilodalton polypeptide.

Animals↗

Papovavirus in epitheliomas appearing on lymphoma-bearing hamsters: lack of association with horizontally transmitted lymphomas of Syrian hamsters.

Several epizootics of lymphoma occurred in a colony of LVG hamsters contaminated with an unusual, horizontally transmitted, subviral, lymphomagenic agent. Hamsters with horizontally transmitted lymphoma, or others housed with these hamsters, occasionally developed epitheliomas bearing an unclassified papovavirus. The possibility that the virus present in the wart-like structures in our hamster colony could activate lymphoma was tested, and a search was conducted for mature virions in passaged epitheliomas and lymphomas. The agent responsible for the skin epitheliomas in our hamster facility was an icosahedral, 36-nm virion compatible with the morphology of a polyomavirus or simian virus 40. Horizontally transmitted lymphoma cells and epitheliomas contained hamster papovavirus (HaPV) DNA sequences detected by dot hybridization; however, such sequences were not found in extracts of lymphomas with oncogenic potential. In contrast to reports by other investigators, infection of hamsters with the papovavirus present in primary epitheliomas produced epitheliomas in good yield but was not reproducibly associated with lymphoma induction. These data confirm the observation that the HaPV is the causative agent of epitheliomas, but they suggest clearly that HaPV is not the agent responsible for lymphomagenesis.

Animals↗

Differential extraction of tumor-specific transplantation antigen and embryonic antigen from simian virus 40- and adenovirus 7-induced sarcoma cells of hamsters with 1-butanol and 3 M potassium chloride.

Simian virus 40 (SV40)-induced sarcomas and adenovirus 7-induced sarcomas (Adv-7) exhibit both specific tumor-specific transplantation antigens (TSTA) and cross-protective embryonic antigens at the cell surface in the LAK:LVG(SYR) strain of Syrian golden hamsters. Specific SV40 TSTA could be released from the surfaces of living hamster sarcoma cells in a 2.5% crude 1-butanol extract (CBE) and served as immunogen to protect syngeneic recipients against subsequent homologous but not heterologous tumor cell challenge. The CBE-extracted SV40-induced TSTA (tumor-specific) was observed to be free of detectable, cross-protective embryonic antigens (EA) by tumor transplantation assays. The induction of cytotoxic lymphocyte-mediated immunity with the CBE-released TSTA was dependent on the administration of a single sensitizing injection of 12-20 micrograms antigen protein. Higher concentrations (50-1,000 micrograms) of the CBE tumor cell extract, given in a single injection, enhanced tumor growth as did two injections of 12.5 micrograms CBE-extracted SV40-induced TSTA at 1-week intervals. A cross-protective antigen(s), not detected in the CBE tumor extracts, was retained in the intact, 1-butanol-extracted SV40 and Adv-7-induced tumor cell lines after completion of the CBE extraction procedure and in similarly extracted 10-day hamster fetal cells. Some alterations in the normal immunogenicity of EA extracted with CBE followed by KCI from SV40-induced sarcoma cells could be detected in the transplantation assays and lymphocyte transformation assays, whereas EA extracted from CBE-KCI-treated Adv-7 cells or 10-day hamster fetal cells retained normal immunogenicity in vivo and in vitro. These procedures provide a means for successful separation of immunogenic SV40- and Adv-7-induced TSTA from detectable, biologically active, cross-protective EA from the surfaces of these sarcoma cells.

1-Butanol↗

Lymphoma-associated ulcerative bowel disease in the hamster (Mesocricetus auratus) induced by an unusual agent.

In a hamster model of non-Hodgkin's lymphoma which closely parallels the disease in man, and which is induced by an unusual agent(s), a diarrheal bowel disease was a major cause of mortality. This study was initiated to characterize this bowel disease and its relation to lymphoma induction and to natural diseases seen in the hamster. The studies showed that the bowel disease was an ulcerative process and was distinct from natural diseases. The incidence of the bowel disease correlated directly with that of the lymphoma in repeated epizootics, in titration studies, and in agent inactivation tests. The ulcerative bowel lesions were seen at the same stage of the disease as acute and chronic inflammatory infiltrates with necrosis in the thymus and mesenteric lymph nodes. Since necrosis in the gut-associated lymphoid tissue can lead to perforation and sepsis, these bowel lesions were lethal, whereas similar necrosis in other lymphoid tissues (thymus and lymph nodes) could be clinically undetectable. Similar lesions have been reported in man. The ulcerative bowel disease was a reliable early clinical marker for exposure of hamsters to this lymphomagenic agent(s).

Animals↗

Embryonic antigens in malignancy and pregnancy: common denominators in immune regulation.

There is mounting that the majority of malignant tumours of humans and rodents carry embryonic determinants (EA) associated with the cell membrane. The evolutionary and developmental purpose of these determinants seems to be related to their biochemical and structural role in the cell membrane. True EAs are uniquely expressed on germinal, embryonic and some fetal cell membranes and are not expressed in adult tissues nor in regenerating tissues. The immunological role of EA in fetal development in utero is still obscure. It is known that maternal IgG and cytotoxic T lymphocytes are produced in response to EA expressed in utero. Immunoregulatory interactions between suppressor, helper and cytotoxic T lymphocytes sensitized to EA during pregnancy have been detected in mice and hamsters bearing a variety of tumours. The same immunological events may occur in humans. The biological product of the retrogenic process that leads to the expression of EA in the emerging malignant cell clone seems to be intimately associated with the promotion of tumour-protective immune responses in the host which mimic the immune responses in pregnancy aimed at protecting the EA+ fetus from maternal immune attack. The description of the immunoregulatory perturbations generated by EA during the induction of cancer may eventually provide effective and predictable attack points for immunological intervention in the control of malignancy. This paper describes methods for detecting EA and considers some immunoregulatory traits found in response to EA expression.

Animals↗

Improved facility and sensitivity in the use of guinea pigs for the isolation of Legionella pneumophila from cooling tower water.

The established criteria for the determination of the optimum time for the sacrifice of guinea pigs inoculated with samples of cooling tower water were found to be inadequate for the detection of low levels of Legionella pneumophila. By ignoring the requirement for fever and by sequentially sacrificing the infected guinea pigs on days 3 through 5 postinoculation, we simplified the procedure, and the sensitivity of detection was improved a great deal.

Air Conditioning↗

B-cell and T-cell lymphomas and other associated diseases induced by an infectious DNA viroid-like agent in hamsters (Mesocricetus auratus).

Five epidemics of diffuse, poorly differentiated lymphocytic, immunoblastic, and plasmacytoid lymphoma induced by an infectious, horizontally transmitting viroidlike agent have occurred in two hamster facilities. Incidence summaries and pathologic characteristics of the lymphomas induced in LSH and LVG hamsters are presented. An elevated leukocyte count with a marked increase in neutrophils and a significant decrease in small mononuclear lymphocytes was detected in 5-week-old but not in 10- or 25-week-old LVG hamsters born in the facility contaminated with the lymphoma-inducing agent. Three-week-old LVG hamsters exposed to the contaminated facility showed no similar hematologic change at 5 weeks of age or 5 weeks of exposure. Several associated syndromes, including an intussusception disease, pyelonephritis, inflammatory bowel disease, and body warts associated with the presence of the causative viroidlike agent in the contaminated colonies are described. Details of the epidemiology of the disease, karyology, viral studies, and correlation with several epidemics in other laboratories are presented.

Animals↗

Unusual filterable oncogenic agent isolated from horizontally transmitted Syrian hamster lymphomas.

An outbreak of horizontally transmitted malignant lymphoma in an experimental hamster holding facility was previously reported. Retroviridae (oncornavirus) or other conventional oncogenic viruses (oncodnaviruses) could not be detected in these lymphomas by immunological methods, direct isolation procedures or electron microscopy but an infectious agents was clearly involved. The incidence of lymphomas during five recurrent epidemics ranged from 50 to 90% in young, inbred and random-bred Syrian golden hamster exposed. The agent seemed to be resistant to UV inactivation, formaldehyde vapour and other viricidal agents (chlorine and iodine), and stable for long periods in the absence of hamster hosts in the contaminated facility. Associated disease syndromes in exposed hamster included severe enteritis, pyelonephritis, the occasional appearance of warts, poor breeding efficiency and intussusception. We now report the successful, cell-free isolation of an unusual, filterable agent prepared in protamine sulphate buffer from primary and animal-passaged lymphomas, which produces lymphomas with good efficiency when injected subcutaneously (s.c.) into newborn Syrian inbred (LSH) and random-bred (LVG) hamster. The agent could be reisolated from these induced lymphomas and injected into other hamsters to reproduce the neoplastic condition. It showed characteristics suggested for a mammalian viroid (a non-encapsidated, DNase-sensitive low-molecular-weight, disease-causing, self-replicating, naturally infectious nucleic acid).

Age Factors↗

Virus-induced cellular immunity to simian virus 40 tumor-specific surface antigen(s) in adult LVG:LAK hamsters.

Cell-mediated immunity directed against simian virus 40 (SV40) tumor-specific surface antigen(s) (TSSA) was detected in SV40-immunized noninbred LVG:LAK hamsters with the use of a lymphocyte transformation assay. Sensitized spleen cells underwent a proliferative response in the presence of cells of an SV40-induced hamster sarcoma cell line (WF5-1) or the plasma membranes from these cells. In addition, 3-M KCl extracts of the plasma membranes of WF5-1 cells elicited such a lymphocyte proliferative response. Neither the cells of a chemically induced sarcoma cell line (OBT), their plasma membranes, nor 3-M KCl extracts of these membranes caused a similar proliferative response. These results established that immunization of adult hamsters with SV40 resulted in a specific autochthonous cell-mediated immune response against SV40 TSSA. The in vitro demonstration of this virus-induced immunity provided a unique method for the investigation of the SV40 TSSA involved in the establishment or rejection of tumors. The described lymphocyte transformation assay was also used to follow the solubilization and purification of the SV40 TSSA.

Animals↗