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Biomedical subjects

L F Lee

Publications and source records attributed to L F Lee.

At least 73 records · Page 4Linked to original sources
PubMed1983

A monoclonal antibody reactive with Marek's disease tumor-associated surface antigen.

An antibody-secreting hybridoma, RPH-6, to Marek's disease tumor-associated surface antigen (MATSA) was produced by somatic-cell hybridization between the mouse myeloma SP2/O-Ag/14 and spleen cells from MSB1 immunized mice. The antibody reacted with 95 to 100% of the cells from eight of 10 chicken MD cell lines and one of two turkey MD cell lines. It did not react with chicken MD cell lines RP1 and SK3, turkey MD cell line RP19, lymphoid leukosis (LL) cell lines, RP9 and RP12, and reticuloendotheliosis virus (REV) cell line RP14. A weak reaction was observed with REV cell line RP13 (10 to 20%), and a very slight reaction with normal chicken spleen cells (1 to 5%). RPH-6 produces immunoglobulin of the IgM class. Cell culture and mouse ascitic fluids have titers of 10(2) and 10(6), respectively, by fluorescent antibody (FA) test against MD tumor cell lines. The antibody did not react with Marek's disease virus (MDV) internal antigen or membrane antigen as detected by indirect FA test on chicken embryo fibroblast cultures grown on coverslips. The 51Cr release assay showed RPH-6 is highly cytotoxic (60% release) only against MD lymphoblastoid cell lines, with antibody prepared from mouse ascites having a cytotoxic titer approaching 10(6). Results from using RPH-6 for differential diagnosis of chicken lymphoid tumors of unknown origin were in complete agreement with those obtained with rabbit anti-MATSA reference serum and pathologic diagnosis.

Animals↗
PubMed1982

The mechanism of genetic resistance to Marek's disease in chickens.

Genetic resistance to Marek's disease in RPL line-6 chickens is expressed not only at the level of host immunological responses against virus an tumour antigens, but also at the level of target lymphoid cells for virus infection and transformation. The nature of the target cell involved was investigated. Spleen cells from susceptible line-7 chickens adsorbed more Marek's disease virus and turkey herpesvirus in vitro than line-6 spleen cells. In the case of Marek's disease virus this was reflected in the replicative ability of the virus in vivo. Transplantation of thymus fragments from 1-day-old line-7 chickens into thymectomized line-6 chickens conferred a high degree of susceptibility on the latter, but the transplantation of spleen or fragments had no significant effect. The reverse procedure, i.e. grafting of line-6 thymi into line-7 chickens, did not diminish the susceptibility of the recipients. In each treatment group the observed titres of leukocyte-associated viraemia correlated with the susceptibility of the group to Marek's disease. Histologically the grafted thymus fragments became depleted of lymphocytes immediately after transplantation. By 6 days there was substantial recovery, apparently as a result of re-population of the thymic epithelium by host stem cells. This was confirmed by transplanting thymus fragments between individuals of opposite sexes. Karyotype analysis showed that the thymus contained lymphocytes of the sex of the recipient. However, karyotype analysis of lymphoma cells taken from recipient line-6 chickens that had received thymus grafts from line-7 birds of the opposite sex showed that, in the majority of cases, the lymphomas consisted of cells of donor origin. It is concluded that the susceptibility of line-7 chickens is largely attributable to the greater susceptibility of their T-lymphocytes to infection and transformation by Marek's disease virus, and that this susceptibility can be transferred to genetically resistant line-6 birds by adoptive transfer of the cells in the form of thymus fragments.

Animals↗
PubMed1982

Immunocompetence of chickens during early and tumorigenic stages of Rous-associated virus-1 infection.

A study was designed to determine the effects of congenital infection with the Rous-associated virus-1 (RAV-1) on the immune function chickens during the early and late tumorigenic stages of infection. In another experiment, the effects of niridazole on the immune competence and the tumor incidence in chickens congenitally infected with RAV-1 were studied. Lymphocyte stimulation by phytohemagglutinin, the phytohemagglutinin skin test, the response to immunization with sheep erythrocytes and Brucella abortus, and histological evaluation of lymphoid organs were used to determine the immune competence in normal and infected chickens. Results indicated that both B- and T-cell immune functions during the early and late stages of RAV-1 infection were comparable to those of normal uninfected chickens. Administration of niridazole to congenitally infected chickens at 5 weeks of age for 7 or 21 days had no effect on the T-cell-mediated immunity; however, administration of the drug for 21 days eliminated lymphoma development. Unlike infection with other oncogenic viruses such as those causing Marek's disease and reticuloendotheliosis, infection with RAV-1 caused no detectable immunodepression during the early and late stages of infection.

Animals↗
PubMed1981

Nature of genetic resistance to Marek's disease in chickens.

Infection of line 6 resistant and line 7 susceptible chickens with Marek's disease virus (MDV) resulted in a depressed phytohemagglutinin (PHA) response and the presence of Marek's disease (MD) tumor-associated surface antigen (MATSA) in the spleens. At 6-10 weeks after infection, recovery in PHA response, diminution in the number of MATSA cells, and the presence of significant anti-MATSA immunity were observed in line 6 but not in line 7 chickens. Both lines had antibody-dependent cell-mediated antiviral immunity, but T-cell-mediated antiviral immunity was detected only in line 6 and the surviving line 7 chickens. Lymphoproliferative lesions were found only in line 7 chickens, an virus titers were significantly higher in line 7 than in line 6 chickens and embryos. Lymphoid organ weights and the number of lymphocytes of line 6 were significantly lower than those of line 7. These data suggests that resistance to MD in line 6 chickens was due to a) a deficiency in the aggregate number of target lymphocytes, b) a restriction in the ability to lymphocytes to nonproductively replicate MDV, and c) the involvement of cellular antiviral and antitumor immune responses.

Animals↗
PubMed1981

Suppression of immunologic function and degeneration of lymphoid organs in cyclophosphamide-treated turkeys.

Neonatal administration of 8 to 20 mg of cyclophosphamide (CY) in turkey poults resulted in a marked alteration in the morphologic features of all major lymphoid organs. Cyclophosphamide induced severe deficiency in antibody response to multiple injections of Brucella abortus and sheep RBC and in vitro proliferative response of peripheral blood leukocytes to concanavalin A. The morphologic regeneration of thymus and of thymus-dependent areas was marked in all major lymphoid organs by posttreatment day 15. This regeneration preceded functional recovery of the mitogenic response of peripheral blood leukocytes. The regeneration of the bursa and bursa-dependent areas in other lymphoid organs was minimal through posttreatment day 27. Thus, CY may be used effectively in turkeys as an immunosuppressive reagent.

Animals↗
PubMed1980

Effect of neonatal thymectomy on pathogenesis of herpesvirus of turkeys in chickens.

Effect of immunosuppression on pathogenicity of herpesvirus of turkeys (HVT) in chickens was studied. In three experiments, newly hatched chickens of two genetic strains were surgically thymectmized and gamma-irradiated and then exposed to HVT. Lymphoid cells of thymectomized-irradiated chickens had reduced in vitro mitogenic response; this result indicated that the immunosuppressive regimen caused suppression of T cell function. The immunosuppressed chickens had more circulating HVT and had a slightly higher frequency of microsocpic lesions in peripheral nerves than the intact control chickens, although the intensity of lymphoproliferation remained very mild and no gross lesions or clinical disease was noted during the 5-week observation period. The absence of significant lesion development in an immunosuppressed host indicated that pathogenic potentials of HVT may be limited.

Animals↗
PubMed1979

Depression of vaccinal immunity to Marek's disease by infection with reticuloendotheliosis virus.

The effect of infection with low-virulence, tissue culture-propagated strains of reticuloendotheliosis virus (REV) on protective vaccinal immunity against Marek's disease (MD) lymphomas was investigated. Vaccinated chickens inoculated at hatching with greater than 10(4) focus-forming units of REV and challenged with MD virus were poorly protected against MD lesion development as indicated by protective indices of 53 to 79% for strain CS (P less than 0.05) and 42 to 49% for strain T (P less than 0.01) compared to 78 to 100% for REV-free controls. Furthermore, the response of blood lymphocytes to mitogen stimulation and the antibody response to sheep erythrocytes and Brucella abortus were less in REV-inoculated chickens than in controls. The REV-induced depression of immune responses was more severe in chickens infected with mildly pathogenic strain T than in chickens infected with the apathogenic strain CS and was generally transient with both virus strains. Little or no depression of immune responses was observed in chickens inoculated with less than 10(3) focus-forming units of REV. These studies extend knowledge on the immunodepressive ability of low-virulence REV strains and establish that infection with these viruses depresses certain parameters of MD vaccinal immunity, an important model for cellular immunity against virus-induced neoplasia in the chicken.

Animals↗
PubMed1979

Macrophage restriction of Marek's disease virus replication and lymphoma cell proliferation.

Macrophages are shown to restrict the replication of Marek's disease virus (MDV) and isotope uptake by spleen cells from chickens bearing Marek's disease (MD) tumors. The titer of virus from duck embryo fibroblasts (DEF) co-cultivation with MDV-spleen cells pretreated to deplete marcophages was 4- to 18-fold higher than with untreated cells. Treated MDV-spleen cells increased isotope uptake by 2-fold. These restrictive activities are attributable to macrophage regulation of cell proliferation.

Animals↗
PubMed1978

A phosphonoacetate-resistant mutant of herpesvirus of turkeys.

A phosphonoacetate (PA)-resistant mutant of the herpesvirus of turkeys (HVT) was isolated and characterized. The mutant of HVT resistant to PA (HVTpa) replicated in duck embryo fibroblast (DEF) culture in media containing 300 microgram PA/ml, whereas the replication of the wild type of HVT (HVTwt) was completely inhibited in DEF culture in media containing 100 microgram PA/ml. The HVTpa was distinct from the HVTwt in plaque morphology, but was indistinguishable antigenically and showed in vitro temperature sensitivity at 41 degrees C (3741 degrees C efficiency of replication was about 5). It replicated poorly in chickens and failed to provide complete protection against challenge with Marek's disease virus (MDV). The HVTpa-induced DNA polymerase had an apparent inhibition constant for PA, an apparent inhibition constant for pyrophosphate, and an apparent Michaells constant for dCTP about 10, 2, and 2.5 times, respectively, greater than the constants for the HVTwt-induced enzyme and was also more thermolabile.

Animals↗
PubMed1978

Inhibition of herpesvirus replication and herpesvirus-induced deoxyribonucleic acid polymerase by phosphonoformate.

Phosphonoformate was found to be an inhibitor of the deoxyribonucleic acid polymerase induced by the herpesvirus of turkeys. The apparent inhibition constants were 1 to 3 muM. Phosphonoformate was also able to block the replication in cell culture of Marek's disease herpesvirus, the herpesvirus of turkeys, and herpes simplex virus. It was as effective as phosphonoacetate. Phosphonoformate was not an effective inhibitor of a phosphonoacetate-resistant mutant of the herpesvirus of turkeys nor of its induced deoxyribonucleic acid polymerase.

Catalysis↗
PubMed1978

Suppression and enhancement of mitogen response in chickens infected with Marek's disease virus and the herpesvirus of turkeys.

The kinetics of phytohemagglutinin (PHA) response of peripheral blood lymphocytes from chickens infected with oncogenic Marek's disease (MD) virus (MDV) or nononcogenic herpesvirus of turkeys (HVT) was studied with a whole blood microassay. At about 7 days after inoculation, a depression in PHA response was observed in MDV-inoculated resistant line N or susceptible line 7(2) chickens and in HVT-inoculated line 7(2) chickens. All chickens initially regained their PHA responsiveness. Susceptible chickens that died of MD or developed MD lymphoma in later stages of virus infection showed a second severe depression in PHA response. No depression was observed in HVT-vaccinated chickens when challenged with MDV. The PHA response of MDV-inoculated chickens that survived MD, HVT-inoculated chickens, and HVT-vaccinated MDV-challenged chickens showed evidence of enhancement. The depression of PHA response was studied and was attributed to the suppressive effect of macrophages on T-cell response, a finding consistent with our previous studies on MDV suppression of PHA response.

Animals↗
PubMed1978

Altered biological and biochemical properties of a phosphonoacetate-resistant mutant of herpesvirus of turkeys.

A phosphonoacetate (PA)-resistant mutant of the herpesvirus of turkeys (HVT) was isolated and characterized. The mutant (HVTpa) replicates in growth medium containing 300 microgram/ml of PA and shows in vitro temperature sensitivity at 41 degrees C (its 37 degrees C/41 degrees C efficiency of replication is about 5). HVTpa replicates poorly in chickens and fails to provide complete protection against MDV challenge. The HVTpa-induced DNA polymerase has an apparent inhibition constant for PA 10 times as great, an apparent inhibition constant for pyrophosphate, twice as great, and an apparent Michaelis constant for dCTP 2.5 times as great as the respective figures for the HVTwt-induced enzyme. The HVTpa-induced enzyme is also more thermolabile.

Animals↗
PubMed1978

Suppression of mitogen-induced proliferation of normal spleen cells by macrophages from chickens inoculated with Marek's disease virus.

Spleen cells from chickens 7 days after inoculation with Marek's disease virus (MDV) responded poorly to stimulation by phytohemagglutinin (PHA). Addition of these cells to syngeneic normal spleen cells caused of marked suppression of the PHA response of the normal cells. The MDV spleen cells also inhibited the DNA synthesis of MSB-1 lymphoblastoid cells in vitro. The suppressive activity is attributed to the presence in MDV spleen cells of a population of suppressor cells with characteristics typical of macrophages. The suppressor cell activity was not removable by treatment with anti-T or anti-B serum with C, but it was reversible by treatment with carrageenan or carbonyl iron/magnet, by passage through glass wool column, and by adherence to plastic Petri dishes. The adherent MDV spleen cells also showed strong suppressor cell activity against syngeneic normal spleen cells.

Animals↗
PubMed1977

Isolation from a transmissible lymphoid tumour (TLT) lymphoblastoid cell line of a herpesvirus similar to Marek's disease virus.

A chicken lymphoblastoid cell line (TLT)-6855 originally established from an avian oncornavirus-induced lymphoma (Siegfried and Olson, 1972) was studied for the presence and expression of Marek's disease virus (MDV) genome. By nucleic acid hybridization a significant amount of MDV DNA was found in this cell line. This virus DNA, however, was not expressed in either virus-specific intracellular or membrane antigens or the MD-associated tumour-specific surface antigen (MATSA). Moreover, MDV-specific antigens could not be activated in this cell line by treatment with 5-IdUrd. In several experiments, when chickens were inoculated with the cell line a herpesvirus was repeatedly isolated from the kidneys. This herpesvirus was antigenically similar to MDV but was low in oncogenicity for chickens.

Animals↗
PubMed1977

Suppressive effect of cyclophosphamide on the T-cell system in chickens.

Neonatal administration of 16 mg of cyclophosphamide in inbred chickens resulted in a transient, but profound, deficiency in the in vitro proliferative response of spleen cells. Functional T-cell deficiency was accompanied by a marked morphological degeneration in the thymus and thymus-dependent areas in the spleen.

Animals↗
PubMed1976

Mechanism of phosphonoacetate inhibition of herpesvirus-induced DNA polymerase.

Phosphonoacetate was an effective inhibitor of both the Marek's disease herpesvirus- and the herpesvirus of turkey-induced DNA polymerase. Using the herpesvirus of turkey-induced DNA polymerase, phosphonoacetate inhibition studies for the DNA polymerization reaction and for the deoxyribonucleoside triphosphate-pyrophosphate exchange reaction were carried out. The results demonstrated that phosphonoacetate inhibited the polymerase by interacting with it at the pyrophosphate binding site to create an alternate reaction pathway. A detailed mechanism and rate equation for the inhibition were developed. For comparison to phosphonoacetate, pyrophosphate inhibition patterns and apparent inhibition constants were determined. Twelve analogues of phosphonoacetate were tested as inhibitors of the herpesvirus of turkey-induced DNA polymerase. At the concentrations tested, only one, 2-phosphonopropionate, was an inhibitor. The apparent inhibition constant for it was about 50 times greater than the corresponding apparent inhibition constant for phosphonoacetate. DNA polymerase alpha of duck embryo fibroblasts, the host cell for the herpesviruses, was inhibited by phosphonoacetate. The apparent inhibition constants for the alpha polymerase were about 10-20 times greater than the corresponding inhibition constants for the herpesvirus-induced DNA polymerase. Duck DNA polymerase beta, Escherichia coli DNA polymerase I, and avian myeloblastosis virus reverse transcriptase were not inhibited by phosphonoacetate.

Acetates↗
PubMed1976

Effect of phosphonoacetate on Marek's disease virus replication.

Phosphonoacetate (PA), but not any of its analogues tested, effectively inhibited avian herpesvirus replication and viral DNA synthesis in cell cultures. At 100 mug/ml culture medium, PA completely inhibited the replication of Marek's disease virus (MDV), herpesvirus of turkeys, and owl herpesvirus, but had no measurable effect on normal cell growth. PA also inhibited DNA polymerases induced by these avian viruses. Enzyme inhibition was 50% at a PA concentration of 0.2 mug/ml. At a concentration of 3-6 mug/ml, the compound also effected a 50% inhibition of alpha (maxi) enzyme of the host DNA polymerase. It had no effect on the host beta (mini) enzyme. When administered to chickens, PA did not inhibit the replication of MDV, nor did it prevent the development of lymphoma.

Acetates↗