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Biomedical subjects

R C Seeger

Publications and source records attributed to R C Seeger.

At least 145 records · Page 8Linked to original sources
PubMed1979

Monocyte subsets in neonates and children.

Volumetrically distinct subpopulations of peripheral blood monocytes, termed M1, M2, and M3, were identified in healthy normal adults and children. Because normal neonates have abnormal monocyte chemotaxis, it was determined whether monocyte subpopulations have different chemotactic capabilities and, if so, whether chemotactically active subpopulations were quantitatively deficient in neonates. Chemotaxis tests with zymosan-activated normal human serum as the chemoattractant and purified monocyte subpopulations revealed that large M3 monocytes were capable of significantly more directed migration than were small M1 and M2 monocytes. Volumetric analysis of monocytes from normal newborns rather than demonstrating an absence of M3 cells revealed that these cells were the predominant monocyte subpopulation. Therefore, we conclude that the impaired chemotactic ability of newborn monocytes is due to a functional rather than quantitative deficiency of M3 cells.

Adult↗
PubMed1977

Microassay using radioiodinated protein A from Staphylococcus aureus for antibodies bound to cell surface antigens of adherent tumor cells.

A new microassay which utilizes radioiodinated staphylococcal protein A (SpA) to detect antibodies bound to cell surface antigens (CSA) was developed for monolayers of viable cultured tumor cells. Optimal detection of bound antibodies occurred at 37 degrees C with incubation periods of one hour each for antiserum and 131I-SpA. Labelling target cells with 125I-iododeoxyuridine facilitated expression of results relative to tumor cell number or protein concentration. Quantitation of antibody depended on CSA (tumor cells) and 131I-SpA being in excess of antibody; under these conditions, 0.25 ng of cell surface bound antibody could be detected readily. Initial studies utilized cultured human neurobodies in human serum which bound to CSA were removed by absorption with glutaraldehyde-insolubilized fetal calf serum (FCS) suggesting that FCS or FCS-like determinants can be CSA. Rabbit antisera, after extensive absorption, bound to cultured neuroblastoma and lung adenocarcinoma cells in a cell type specific pattern. These experiments demonstrated the value of this assay in quantitating anti-CSA antibodies and in serological analysis of tumor CSA.

Adenocarcinoma↗
PubMed1977

Abnormalities of the immune system in children with neuroblastoma related to the neoplasm and chemotherapy.

Children with localized and metastatic neuroblastoma were studies to determine their immune status at the time of diagnosis and while they were receiving intensive intermittent chemotherapy; Investigations included leukocyte and differential counts, delayed hypersensitivity response, quantitative serum immunoglobulins, percentages of T and Fc receptor lymphocytes, PHA-induced mitogenesis, and antibody-and PHA-dependent cellular cytoxicity. Abnormalities related to the neoplasm at diagnosis were limited to depressed leukocyte and lymphocyte counts and increased concentrations of serum IgM in patients with metastases to bone marrow and other sites. No abnormalities were observed in those with localized tumors. Intermittent chemotherapy of metastatic neuroblastoma caused immunosuppression. Effects were most marked during five-day courses of chemotherapy; they included abrogation of DH and decreased leukocyte and lymphocyte counts and percentages of Fc receptor lymphocytes. Recovery of DH with partial recovery of leukocyte and lymphocyte counts was observed three weeks, later, prior to the next course, We conclude that both metastatic tumor and chemotherapy cause abnormalities of the immune system in children with neuroblastoma.

Antibodies, Neoplasm↗
PubMed1977

Adrenergic, cholinergic, and inactive human neuroblastoma cell lines with the action-potential Na+ ionophore.

Cultured human neuroblastoma cell lines were assayed for biochemical characteristics of neuonal function. Cell lines studied included LA-N-1, LA-N-2, IMR-32, SK-N-SH, and SK-N-MC. Veratridine-dependent uptake of 22Na+ implied the presence of the action potential Na+ ionophore in LA-N-1, LA-N-2, IMR-32, and SK-N-SH. The time course of 22Na+ uptake and inhibition of uptake by tetrodotoxin supported this. SK-N-MC had no veratridine-dependent 22Na+ uptake. Tyrosine hydroxylase (EC 1.14.10.), glutamic acid decarboxylase (EC 4.1.1.15), and acetylcholine contents in neuroblastoma cells were compared to those in brain. LA-N-1 and IMR-32 contained 15 and 5 times as much tyrosine hydroxylase, respectively, whereas LA-N-2, SK-N-SH, and SK-N-MC contained only 0.5 to 5% of that in brain. Acetylcholine was present in -LA-N-2 in 15- to 20-fold greater quantities than in brain; other lines had only 10 to 50% of that in brain. None of the cell lines contained glutamic acid decarboxylase. Thus, continuously propogated human neuroblastoma cell lines may have the action potential Na+ ionophore and may be adrenergic (LA-N-1 and IMR-32), cholinergic (LA-N-2), or inactive (SK-N-SH and SK-N-MC). This is the first demonstration of the action potential Na+ ionophore and of acetylcholine production in human neuroblastoma cell lines.

Acetylcholine↗
PubMed1977

Inhibition of antibody-dependent cellular cytotoxicity by protein A from Staphylococcus aureus.

Protein A, a cell wall constituent of several strains of Staphylococcus aureus, binds strongly to the Fc portion of immunoglobulins. This investigation demonstrated that such binding can inhibit antibody-dependent cellular cytotoxicity (ADCC). The degree to which ADCC was inhibited depended upon the relative concentrations of protein A and anti-target cell antiserum. Protein A also inhibited the formation of rosettes between antibody-coated sheep red blood cells and lymphoid cells with Fc receptors. We, therefore, conclude that protein A inhibits ADCC by preventing the binding of antibody-coated target cells to Fc receptors on cytotoxic effector cells.

Antibodies↗
PubMed1977

Morphology, growth, chromosomal pattern and fibrinolytic activity of two new human neuroblastoma cell lines.

Neuroblastoma cell lines LA-N-1 and LA-N-2 were extablished from neuroblastoma cells in the bone marrow and in the primary tumor, respectively, of two children with metastatic neuroblastoma. Morphology, growth in vitro and in athymic nude mice, chromosomal patter, and fibrinolytic activity of these cell lines and of previously extablished human neuroblastoma cell lines IMR-32, SK-N-MC, and SK-N-SH were compared. Most LA-N-1 cells were tear-drop shaped, small cells with processes; they tended to grow in clusters. LA-N-2 was comprised of elongated cells and small round cells, the latter growing in dense clumps on the former. Electron microscopy revealed numerous cytoplasmic dense cores in many LA-N-1 cells but none in LA-N-2 CELLS. During logarithmic growth in vitro, doubling times for LA-N-1, LA-N-2, SK-N-MC, SK-N-SH, and IMR-32 cells were 32,56, 23, 36, and 26 hr, respectively. Cells of all lines formed colonies in soft agar, and, after variable latency periods, LA-N-1, LA-N-2, SK-N-MC, and IMR-32 cells formed tumors in athymic nude mice. The marker chromosome(s) characteristic of each cell line was present in more than 90% of cells of given line. Significant plasminogen-dependent fibrinolytic activity was present in cells of all lines. These studies indicate that LA-N-1 and LA-N-2 cells arose from single but different aberrant progenitor cells and that they have properties of neuroblastoma cells. They also demonstrate that cell lines derived from human neuroblastomas are heterogenous as are the tumors in children.

Animals↗
PubMed1976

Severe combined immunodeficiency with B lymphocytes: in vitro correction of defective immunoglobulin production by addition of normal T lymphocytes.

A 6 1/2-month-old male with severe combined immunodeficiency (SCID) had a low percentage and number of T cells (11%; 241/mm3) and a high percentage and number of B cells (52%; 1187/mm3) and null cells (37%; 868/mm3). In vitro studies were performed to determine if this child's primary defect involved differentiation of both T and B lymphocytes or if failure of B lymphocytes to differentiate into immunoglobulin producing cells was secondary to T lymphocyte abnormalities. Immunoglobulin production by lymphocytes in response to polyclonal mitogens (pokeweed mitogen and foetal calf serum) was measured by pulse-labelling cells with 3H-leucine and then precipitating cytoplasmic and secreted immunoglobulins with polyvalent anti-human immunoglobulin and S. aureus (Cowan strain I) protein A. The patient's lymphocytes did not synthesize immunoglobulins in vitro in response to mitogens. They did not suppress synthesis of immunoglobulins by normal lymphocytes. However, addition of normal purified T cells, which themselves did not synthesize immunoglobulins, enabled the patient's B lymphocytes to become immunoglobulin synthesizing and secreting cells. Gamma, mu, and light chains were secreted. This suggests that the primary abnormality was in the T-cell axis at the level of lymphoid stem cells or prothymocytes and that failure of B lymphocytes to become immunoglobulin-producing cells was secondary to this defect.

Antibody-Producing Cells↗
PubMed1976

Disease and non-disease-related cell-mediated cytotoxicity in humans.

The human bladder cancer/T24 system was used to investigate disease and non-disease-related cell-mediated cytotoxicity (CMC). CMC was determined in a modification of the microcytotoxicity assay of Takasugi and Klein. Analysis of data of groups of patients confirmed previous findings that effector cells (EC) from bladder cancer patients were more cytotoxic against T24 than were EC from normal individuals or from patients with other genitourinary cancers. Differences between patients with bladder cancer and other patients were not observed for other target cells. During the course of these experiments, non-disease-associated CMC by EC from individual normal donors and patients was observed. This phenomenon was investigated to determine its reproducibility and its relationship to different methods of preparing EC. Reproducibility of non-disease-related CMC was ascertained using EC prepared from heparinized blood by centrifugation over Ficoll-Hypaque (FH). A total of 126 experiments were performed in which 18 normal donors were tested 2 to 7 times each against 4 target cell lines. Of the resulting 46 combinations or groups of repeated assays, only 7 showed significant variability. Each normal donor had consistent CMC with differences from others being reproducible. CMC was therefore not due to crowding or physical effects. CMC mediated by EC prepared in this manner was then compared to that mediated by EC prepared by other methods in simultaneous tests.

Cell Line↗