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R C Seeger

Publications and source records attributed to R C Seeger.

152 records · Page 9Linked to original sources
PubMed1970

Synergistic interaction of macrophages and lymphocytes in antigen-induced transformation of lymphocytes.

The role of macrophages and lymphocytes in antigen-induced transformation of lymphocytes has been investigated. Lymphocytes and macrophages were obtained from inbred strain 13 guinea pigs which were either unimmunized or immunized with complete Freund's adjuvant (CFA) or tetanus toxoid in CFA. The transformation response to PPD or tetanus toxoid was assayed by tritiated thymidine incorporation. Addition of macrophages to immune lymphocytes significantly increased their response to purified protein derivative (PPD) or tetanus toxoid. This was observed if the macrophages were (a) "immune" or "nonimmune", (b) unirradiated or irradiated (3000 R), (c) 99% pure, and (d) peritoneal or alveolar in origin. Neither immune nor nonimmune macrophages were able to induce nonimmune lymphocytes to respond to PPD or tetanus toxoid. When macrophages were incubated with PPD or tetanus toxoid and then washed, they stimulated immune lymphocytes to transform. An incubation time of (1/2) hr was adequate, however, 2-4: hr was optimal. These studies indicate (a) that antigen-induced transformation of lymphocytes is greatly enhanced by macrophages; (b) that macrophage-antigen interaction can antecede lymphocyte-antigen interaction and results in macrophages which are able to stimulate lymphocyte transformation; and (c) that the immunological memory requisite to elicit specific transformation responses is a property of the lymphocyte and not the macrophage.

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PubMedDate not supplied

Metastatic sites in stage IV and IVS neuroblastoma correlate with age, tumor biology, and survival.

PURPOSE: The goal of this study was to determine the incidence of metastatic sites in neuroblastoma and the extent to which metastatic sites correlate with age, tumor biology, and survival. PATIENTS AND METHODS: All 648 patients with stage IV and IVS neuroblastoma registered on Children's Cancer Group protocols 3881 and 3891 were analyzed. Metastatic site data were provided by treating institutions and reviewed in patients with central nervous system (CNS), intracranial, lung, or "other" metastases. RESULTS: The incidence of metastatic sites at diagnosis was 70.5% in bone marrow, 55.7% in bone, 30.9% in lymph nodes, 29.6% in liver, 18.2% in intracranial and orbital sites, 3.3% in lung, and 0.6% in CNS. Event-free survival (EFS) was decreased in patients with bone, bone marrow, CNS, intracranial/ orbital, lung, and pleural metastases, and improved in those with liver and skin metastases. In infants, MYCN amplification and unfavorable Shimada histopathology correlated with increased frequencies of bone and intracranial or orbital metastases. In older patients, MYCN amplification correlated with increased frequencies of intracranial or orbital, liver, and lung metastases. Multivariate analysis revealed that metastatic site is not an independent prognostic factor. CONCLUSIONS: Metastatic pattern in neuroblastoma differs with age and correlates with tumor biological features and EFS. These correlations could reflect changes in host or tumor biological features with age resulting in differences in metastatic capacity or tumor affinity for specific sites.

Adolescent↗
PubMedDate not supplied

Antineuronal antibodies in patients with neuroblastoma and paraneoplastic opsoclonus-myoclonus.

PURPOSE: To identify serologic markers in children with paraneoplastic opsoclonus-myoclonus (POM). MATERIALS AND METHODS: We examined the sera of 64 children with neuroblastoma (16 with POM and 48 age-matched and stage-matched controls) by immunohistochemistry of rat brain and human cerebellum, and by Western blot analysis of protein extracts from human Purkinje cells, cortical neurons, neuroblastoma cell lines, and HuD. RESULTS: Using immunohistochemistry, IgG reactivity against neurons was identified in 13 of 16 POM sera (81%), and 12 of 48 non-POM sera (25%; P<0.001). IgM antineural antibodies were present in 3 of 16 POM sera (19%) and 11 of 48 (23%) non-POM sera. Except for anti-Hu antibodies detected in 10 sera (4 with POM), no other specific reactivities were identified by Western blot analysis of neuronal or of neuroblastoma protein extracts. CONCLUSIONS: We conclude that: 1) patients with neuroblastoma and POM are more likely to harbor antineuronal antibodies than patients without POM; 2) no specific serologic marker of POM was identified, but the frequent presence of antineuronal antibodies suggests that POM is immune-mediated; and 3) anti-Hu antibodies are present in some sera from patients with neuroblastoma, irrespective of the presence of POM.

Adult↗
PubMedDate not supplied

A monoclonal antibody recognizing human Thy-1: distribution on human and non-human primate haematopoietic cells.

A monoclonal antibody designated 'antibody 390' (Ab 390) with anti-human Thy-1 reactivity was prepared by the hybridoma technique from the splenocytes of BALB/c mice immunized with human fetal brain. This antibody was shown to have anti-human Thy-1 reactivity because (1) it precipitated a molecule with a molecular weight of about 24,000 daltons, (2) it had a pattern of reactivity similar to that of previously described anti-human Thy-1 antibodies and (3) purified human Thy-1 antigen specifically inhibited binding of Ab 390 to a known antigen-positive cell line. It was the intent of this study to investigate the distribution of Thy-1 on normal and malignant haematopoietic cells in humans and non-human primates. We show here that Ab 390 did not react with human peripheral blood leucocytes, bone marrow cells or splenocytes by immunofluorescence but did react with subcapsular and cortical fetal thymocytes by peroxidase-antiperoxidase immunohistology. A section of fetal spleen demonstrated staining of connective tissue and blood vessels and rare reactive lymphocytes. Adult spleen contained Thy-1-positive cells surrounding the white pulp and in the marginal zone, but single-cell suspensions of splenocytes did not react with Ab 390. Ab 390 was tested against a variety of fresh human leukaemia cells and human cell lines and was shown to react with only the acute lymphoblastic leukaemia T cell lines RPMI 8402 and HPB-MLT. Non-human primate studies revealed reactivity with a number of T cell lines from New World primates (cotton-topped and red-bellied marmosets) and peripheral blood granulocytes (owl monkey). Our studies support previous findings that suggest that human Thy-1 may be a marker for early T lymphocytes in man, and its distribution on non-human primate T cell lines suggests the same for certain species of non-human primates. Not consistent with the distribution on human cells was the demonstration of Ab 390 reactivity with owl monkey granulocytes.

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PubMedDate not supplied

In vitro and in vivo preclinical chemotherapy studies of human neuroblastoma.

Two human neuroblastoma cell lines, LA-N-1 and SK-N-MC growing in vitro and as subcutaneous tumors in athymic nude mice, were evaluated for their sensitivity to cyclophosphamide, doxorubicin (Adriamycin), and vincristine. In vitro, cyclophosphamide, following liver S-9 metabolic activation, and vincristine were significantly more cytotoxic to SK-N-MC than to LA-N-1 cells; doxorubicin was equally cytotoxic to both cell types. Treatment of nude mice bearing LA-N-1 and SK-N-MC tumors with cyclophosphamide and vincristine produced significant reduction (> 50%) in SK-N-MC tumor weights but not in LA-N-1 tumor weights. Doxorubicin failed to produce significant reduction in the weight of either the LA-N-1 or the SK-N-MC tumor. These sensitivities were generally similar to the clinical response of the tumors to these same agents. Such an in vitro and in vivo system using these and other neuroblastoma cell lines may provide a preclinical model for evaluating the activity of chemotherapeutic agents against human neuroblastoma.

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