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Biomedical subjects

H H Fudenberg

Publications and source records attributed to H H Fudenberg.

At least 109 records · Page 6Linked to original sources
PubMed1982

Heterozygosity at Gm loci associated with humoral immunity to osteosarcoma.

Serum samples from 50 Caucasian patients with osteosarcoma were tested for the presence of antibodies to osteosarcoma-associated antigens (OSAA) and typed for nine Gm markers. A highly significant association was found between Gm 3;5,13,14 and unresponsiveness to OSAA, and between 1,3,17;5,13,14,21 and responsiveness to OSAA. These results suggest the existence of complementary immune response genes which in the heterozygous condition permit a response to OSAA.

Antibody Formation↗
PubMed1982

Role of neutrophil antigen NA1 in an infant with autoimmune neutropenia.

A nontransfused 14-month-old female infant was investigated for persistent neutropenia of eight months' duration, with absolute neutrophil counts ranging from 410 to 935 cu mm. The patient's sera reacted with neutrophils from her own peripheral blood, from normal donors, and from her mother, all these having the neutrophil antigen NA 1, but not with neutrophils from NA 1-negative donors, including the father. The autoantibody was detectable by capillary agglutination and by indirect immunofluorescence techniques but not by complement-dependent cytotoxicity. No antibody was found in the mother's serum. Studies on three occasions showed good correlation between the appearance of circulating autoantibody and the peripheral neutrophil counts. Our observations, together with previously published reports, suggest a possible relationship of NA 1 antigen and the disease susceptibility of NA 1-positive infants to autoimmune neutropenia.

Agranulocytosis↗
PubMed1982

Autoantibodies and immunoglobulin allotypes in healthy North American Blacks of different age groups.

A population of 291 healthy North American Black subjects of different ages was studied for immunoglobulin (Ig) allotypes and the prevalence of autoantibodies, to determine possible associations between Ig allotypes and age, autoantibodies and age, and Ig allotypes and autoantibodies. Indirect immunofluorescence was used to detect anti-gastric parietal cell, anti-smooth muscle, anti-thyroid microsomal, anti-nuclear, and anti-mitochondrial antibodies. The sera were typed for the Ig allotypes Gm(1, 2, 3, 5, 6, 13, 14, 17, and 21) and Km(1) with a hemagglutination-inhibition assay. A significant association between advanced age and an increased prevalence of anti-nuclear antibodies was observed in females. There was no significant association between Ig allotypes and the autoantibodies tested. The results suggest that Ig allotypes are not involved in the development of autoantibodies in healthy Blacks.

Adolescent↗
PubMed1982

Bactericidal capacity of polymorphonuclear leukocytes from patients receiving theophylline therapy.

The capacity of polymorphonuclear leukocytes (PMNs) to kill Staphylococcus aureus strains 502 A was studied in 25 patients receiving theophylline therapy and in normal healthy controls. A significant difference in PMN bactericidal capacity was found between controls and patients with serum theophylline levels higher than 8 micrograms/ml, as determined by high-pressure liquid chromatography. The bactericidal capacity of PMNs from both the patient and control populations was reduced in the presence of theophylline levels above 8 micrograms/ml. In addition, a transient but significant drug-independent reduction was found in the bactericidal capacity of transient but significant drug-independent reduction was found in the bactericidal capacity of PMNs from patients receiving theophylline.

Adolescent↗
PubMed1982

Identification of "active" T lymphocytes among effector cells in guinea pigs.

Guinea pig T lymphocytes have receptors of different affinity for rabbit red blood cells (RRBC): those binding RRBC immediately are termed "active" T cells; the remainder, which bind RRBC only after longer incubation times, are "non-active" or "late-rosetting" T cells. We have found that these two subpopulations have different functional characteristics. Active T cells could not be stimulated effectively with phytohemagglutinin (PHA), and stimulation with concanavalin A (ConA) increased their DNA synthesis only at high concentrations. The non-active subpopulation responded better to PHA but poorly to ConA. Unseparated (total) T cells, however, responded well to both mitogens, suggesting a helper effect by the active T cells. The presence of monocytes in T-cell cultures further enhanced mitogen-induced DNA synthesis. Active T cells were not present in guinea pig bone marrow, whereas they constituted 10% of all lymphocytes in the thymus, 13% in the spleen, 29% in lymph nodes, and 32% in the peripheral blood. After administration of antigen in vivo, the number of active T cells in the regional lymph node increased, whereas the number of total T cells did not change. The similarity of the active T cell populations in guinea pigs and humans increases the usefulness of these animals for preclinical tests of potential new immunomodulating agents.

Animals↗
PubMed1982

Does a primary host defense abnormality involving monocytes-macrophages underlie the pathogenesis of lung disease in cystic fibrosis?

The primary cause of morbidity and mortality in cystic fibrosis (CF) patients is chronic pulmonary disease. Pulmonary disease in CF is characterized in part by: (a) obstruction of the bronchi and bronchioles by inspissated secretions (mucus is hypersecreted and may also be abnormal), (b) recurrent or persistent bacterial infections, and (c) a chronic inflammatory state. We propose herein that much of the pathophysiology of lung disease in CF stems from a genetically inherited metabolic defect in monocyte-macrophages (M-Mphi), and we review evidence which indicates that CF M-Mphi are innately metabolically abnormal. Once activated by various stimuli, CF M-Mphi become metabolically hyperactive and hypersecretory as evidenced by the production of excessive levels of a variety of mediators which could have definite roles in both the initiation of pulmonary obstruction and the accelerated development of a chronic inflammatory response in CF. Evidence is also reviewed which indicates that other CF M-Mphi functions crucial to the afferent and efferent phases of the immune response to bacterial infections in the lung may be adversely affected. Mechanisms proposed to explain the abnormal production of mediators by CF M-Mphi are discussed, and it is concluded that hyperproduction of mediators by CF M-Mphi and their metabolic hyperactivity probably result from a defect in autoregulation. The nature of the metabolic defect in CF M-Mphi indicates that CF should be classified as a "new" primary host defense abnormality or alternatively as a "new" primary immune deficiency disease.

Bacterial Infections↗
PubMed1982

Effects of thymosin and evidence of monocyte suppression of both T- and B-cell functions in two cases of 'common variable immunodeficiency'.

We have studied two patients with common variable immunodeficiency (CVID), impaired cell-mediated immunity, and high percentages of monocytes in their peripheral blood. Removal of monocytes from cultures of peripheral blood mononuclear cells from both patients increased the in vitro responses to phytohaemagglutinin (PHA) and concanavalin A (Con A) but not to purified protein derivative (PPD), as measured by [3H]thymidine uptake. Similarly, supernatants of monocyte cultures from both patients, unlike supernatants of normal monocytes, suppressed the in vitro responses to PHA and Con A but enhanced the response to PPD by cultured mononuclear cells from the patients and from normal donors. Addition of unfractionated mononuclear cells from both patients to normal mononuclear cells suppressed both pokeweed mitogen (PWM) stimulation and IgG production; this effect was abrogated by removal of monocytes from the patients' mononuclear cell populations. This effect of thymosin on both patients' mononuclear cells was assayed in vitro. Thymosin was ineffective in vitro with cells from the first patient; for the other patient, [3H]thymidine uptake by mononuclear cells stimulated with PPD increased, whereas uptake by Con A-stimulated cells decreased, as did the percentage of E rosette-forming cells, providing further evidence of heterogeneity of the CVID syndrome. The effects of thymosin were also dependent on monocytes.

Adult↗
PubMed1982

Polyclonal activation of human peripheral blood B lymphocytes by formaldehyde-fixed Salmonella paratyphi B. II. Heterogeneity of B lymphocytes.

B-cell 'activation' in cultures stimulated with pokeweed mitogen (PWM), Staphylococcus aureus strain Cowan I, or formaldehyde-fixed Salmonella paratyphi B (SPB) was evaluated by enumeration of cells secreting immunoglobulin (Ig) and by quantitation of Ig released into culture supernatants. A dissociation between these two values was found after day 6 in cultures activated with PWM or SPB, suggesting that Ig-secreting cells (ISC) are heterogeneous in terms of Ig secretion rate. Generation of ISC in cultures activated with PWM or SPB was partially inhibited by hydroxyurea, but Ig levels in culture supernatants were not affected. These results indicate that there are at least two subpopulations of ISC in stimulated peripheral blood lymphocyte cultures, one sensitive to, and the other resistant to, hydroxyurea. The hydroxyurea-resistant subpopulation appeared to be more mature and to release most all of the Ig detected in culture supernatants. Furthermore, time-course studies of ISC numbers and Ig levels showed that each ISC in SPB-stimulated cultures (but not in PWM-stimulated cultures) was more active in Ig synthesis and secretion after day 8 than before day 6, indicating that after day 8 most of the ISC in cultures activated with SPB were hydroxyurea-resistant. These studies suggest that SPB is another useful polyclonal B-cell 'activator' for studies of human B-cell differentiation and function, and that SPB defines two distinct subsets of B cells.

B-Lymphocytes↗
PubMed1982

Lymphokine production in T-lymphocyte subsets defined by active E-rosette formation.

Human T-cell subsets, defined by active E rosette formation, were examined for their ability to produce leucocyte migration inhibitory factor (LIF) in response to mitogen or specific antigen. It was determined that T cells enriched for active rosette-forming (A+) cells produced LIF in response to concanavalin A, whereas T cells depleted of active rosette-forming (A-) cells did not. Similarly, A+ cells from a tuberculin-sensitive donor produced LIF in response to tuberculin purified protein derivative, whereas A- cells from the same donor failed to produce the mediator. Thus, T-cell production of LIF in humans appears to be restricted to those T cells capable of active rosette formation.

Cell Separation↗
PubMed1982

Fetal cytotoxic antibodies to maternal T-lymphocytes: a possible mechanisms for maternal tolerance of the fetal allograft.

The absolute numbers of B lymphocytes and of total and "active" T lymphocytes in peripheral venous blood (Mv) from 15 females at the time of normal term deliveries were found to be significantly less (p less than 0.001) than in the fetal umbilical vein (Uv) or artery (Ua) or in the peripheral blood of 75 normal nonpregnant controls (Cv), suggesting that maternal cellular immunity at term is lowered. In 19 umbilical artery samples, titers of lymphocytotoxic antibodies (Cyt), expressed as the mean log of reciprocal titer values, were significantly higher (p less than 0.01 in each case)( than in matched maternal samples, against the following cell types: Maternal T cells (7.1 in Ua vs 1.21 in Mv sera); maternal B cells (3.23 vs 1.58); T cells (4.41 vs 1.38) but not B cells from other females at delivery; autologous T cells (2.9 vs 1.0); autologous B cells (1.88 vs 0.69); T (5.39 vs 0.81) and B (2.80 vs 1.25) cells from the paired Uv; T (3.78 vs 0.62) and B (2.64 vs 0.77) cells from the Uv of other newborn infants; and T (4.19 vs 2.0) but not B cells from controls (Cv). The highest Cyt titers in the umbilical artery samples were against maternal T lymphocytes. Immunofluorescence studies indicated that the Cyt antibodies were primarily IgG. Absorption of 13 other Ua sera with maternal T cells eliminated with Cyt activity against both Mv and Cv T cells; absorption with Cv T cells eliminated the reaction against Cv T while reducing cyt titres to Mv T lymphocytes. We conclude that the fetus produces lymphocytotoxic antibody specifically directed against maternal T lymphocytes, in addition to antibody against T lymphocytes of other adults.

Adult↗
PubMed1982

Immunoglobulin allotypes and immune response to meningococcal polysaccharides A and C.

Serum samples were collected from 113 healthy Caucasian volunteers before and after vaccination with meningococcal polysaccharides (MPS) group A and group C. Antibodies to MPS group A and group C were measured and sera were typed for several Gm and Km(1) allotypes. A significant association was found between the Gm 1,3,17; 5,13,14,21 phenotype and low immune responsiveness to MPS group A. These results suggest the possible existence of an immunoglobulin allotype-linked immune suppression (Is) gene(s) in man.

Adult↗
PubMed1982

Human peripheral blood lymphocyte activation by protein A from Staphylococcus aureus.

Mitogenesis and polyclonal immunoglobulin production in peripheral blood lymphocyte cultures activated with Formalin-fixed or autoclaved protein A-containing Staphylococcus aureus were studied. Direct evidence for a dissociation between cell proliferation and polyclonal immunoglobulin production was found, in that S. aureus was not mitogenic after being autoclaved but retained the ability to stimulate B cells to produce immunoglobulin. Trypsin-treated S. aureus lost its binding site for immunoglobulin G, but its mitogenicity was not altered; thus, the protein A binding site for immunoglobulin G on the bacterial cell wall is not required for the stimulation of lymphocyte proliferation. Our data also show a dissociation between cell proliferation and polyclonal immunoglobulin production induced by protein A coupled to Sepharose CL-4B. These results suggest the presence of three distinct active sites on the protein A molecule: one that binds immunoglobulin G molecules, one that stimulates cell proliferation, and one that stimulates polyclonal immunoglobulin production.

B-Lymphocytes↗