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Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 523 records · Page 29Linked to original sources

Circulating immune complexes associated with naturally occurring lymphosarcoma in pet cats.

Cats were classified into 4 categories by immunofluorescence antibody assay for the presence of feline leukemia virus (FeLV) and histologically as a) normal, FeLV-, b) normal, FeLV+, c) lymphosarcoma (LSA), FeLV+, and d) LSA, FeLV-. Determinations by Raji cell radioimmunoassay modified for cat serum revealed circulating immune complex (CIC) levels of healthy cats to be less than or equal to 50 micrograms equivalent aggregated cat immunoglobulin/ml (microgram/ml). In contrast, sera of cats in groups b, c, and d all contained significantly higher CIC levels (up to 12,000 micrograms/ml) associated with marked hypocomplementemia and C activation occurring via the classical pathway. Sera from FeLV+, LSA+ cats with high levels of CIC and sera of healthy cats were fractionated according to size and bouyant density by centrifugation through 10 to 40% sucrose gradients. Analysis of fractions from LSA+, FeLV+ sera revealed that both immune complexes (ICs), FeLV reverse transcriptase (RT), and IgG were present in fractions corresponding to a bouyant density of 1.15 to 1.18 g/ml. The CIC containing fractions activated C by the classical pathway. Sera from normal cats did not have CIC or RT and none of the fractions activated the classical pathway. These data suggest that vital antigen-antibody complexes are present in sera of viremic cats with LSA and these complexes activate the C system.

Animals↗

Geographic and family studies of immunological responses to antigens of the murine mammary tumor virus in sera of patients with breast cancer.

Sera of breast cancer patients from the United States, India, East Africa and China as well as from their families and from healthy women were assayed for antibodies reactive with the murine mammary tumor virus (MuMTV). Detection was by an enzyme-linked immunoassay recently developed in our laboratory. In the women with breast cancer, 62% of the East Africans, 28% of the Indians, 19% of the Americans but only 5% of the Chinese had antibody to MuMTV. Among healthy women, 21% of the Africans, 3% of the Americans and 5% of the Chinese possessed this antibody. Several family members of breast cancer patients, males as well as females, had increased levels of MuMTV antibody. The MuMTV-reactive antibody was removed by absorption with MuMTV, deglycosylated MuMTV and gp52, the major MuMTV envelope protein. It was not absorbed out by murine leukemia viruses, red blood cells from various species, fetal calf serum or carbohydrates. The results suggest that there may be more than one form of breast cancer, definable by reactivity to MuMTV. The murine mammary tumor virus (MuMTV) is the etiological agent of breast cancer in mice. The induction of mammary tumorigenesis, however, is dependent upon the genetic makeup, hormonal status, and diet of the infected mouse. Thus, even in a situation where a known single cause for breast cancer exists, disease manifestation is subordinate to diverse factors in the individual host.

Africa, Eastern↗

Subpopulations of human T lymphocytes. XIII. T cell subpopulations (T mu and T gamma) in children with bronchial asthma.

Peripheral blood from children with bronchial asthma was examined for the proportions of T cells, T cells with receptors for IgM (T mu) or IgG (T gamma), and locomotion of T cells in the presence of chemoattractants casein and endotoxin-activated serum (EAS). Patients were divided into two groups: (A) children with asthma who were not taking any medication for at least 3--5 days prior to the study and (B) children who were taking aminophylline when this study was carried out. Proportions of T cells and T gamma cells in patients from both groups were comparable to age and sex matched controls. T mu cells in group A patients were comparable to those of the control group, but group B patients had significantly lower proportions of T mu cells when compared with those of controls and of patients in group A. Locomotion of T cells in the presence of casein and EAS was comparable in all three groups. The significance of these findings is discussed.

Aminophylline↗

Neuraminidase treatment of human T lymphocytes: effect on Fc receptor phenotype and function.

Purified peripheral blood T cells or T mu cells from normal healthy donors were treated in vitro with neuraminidase and examined for the expression of IgM Fc and IgG Fc receptors. Increasing concentrations of neuraminidase selectively removed IgM Fc receptors, whereas the number of T cells expressing IgG Fc receptors was significantly increased. Following neuraminidase treatment, IgM Fc receptors could be regenerated by reincubation of T cells at 37 degrees C. The regeneration of IgM Fc receptors could be blocked by treatment with cycloheximide. Neuraminidase treatment of purified T mu cells resulted in the expression of IgG Fc receptors on a subpopulation of T mu lymphocytes. A small percentage of the neuraminidase-treated T cells expressed receptors for both IgG and IgM. Treatment of T cells with neuraminidase did not effect T cell-mediated spontaneous cytotoxicity (SLMC) or antibody-dependent cellular cytotoxicity (ADCC). Our results indicate that T cell Fc receptor phenotypes can be modulated in vitro without significantly altering their functional capacity.

Cytotoxicity, Immunologic↗

Nutritional modulation of immune responses.

Malnutrition has been linked in field studies with increased susceptibility to infection, often associated with severe marasmus or kwashiorkor. However, studies by Jose and colleagues revealed an apparent paradox: while B-cell immunity was decreased by chronic moderate malnutrition, several aspects of T-cell immunity were enhanced. In extensive experimental studies we have analyzed the effects of dietary restriction in immunologic function and development of disease. Our investigations may be grouped into three related areas. 1) Differential effects of protein or protein-calorie malnutrition on B-cell and T-cell immunity. While antibody-mediated immunity was impaired in animals moderately restricted with respect to protein or total calories, several T-cell functions were consistently enhanced in mice, rats, guinea pigs, and monkeys. 2) Influence of restricting a single nutritional element, the trace metal zinc, on immunologic function. Zinc deficiency produces progressive thymic involution and a progressive loss of T-cell immunity functions in mice and rats. While congenital failure to absorb this element normally is the single cause of hereditary acrodermatitis enteropathica, a frequently lethal disease both in humans and in cattle, acrodermatitis enteropathica has also been linked with common variable immunodeficiency disease, total parenteral alimentation with preparations lacking zinc, several forms of cancer, marasmus, and kwashiorkor. 3) Inhibition by dietary restriction of development of the diseases of aging. Disorganization of thymus-derived immunity, and development with aging of genetically determined diseases in several strains of mice, can be sharply curtailed or even prevented by reducing the intake of total calories or fat. Similarly, development of mammary cancer in C3H female mice is prevented by restricting dietary intake of fat.

Aging↗

Induction of differentiation in human marrow T cell precursors by the synthetic serum thymic factor, FTS.

The serum thymic factor, 'facteur thymique serique' (FTS), was analysed in vitro for its ability to induce differentiation of normal human marrow T cell precursors into cells with T lymphocyte characteristics. FTS has been isolated, characterized, sequenced and synthesized. In the mouse, natural and synthetic FTS have similar activities in vitro in the rosette inhibition assay. Both substances influence a variety of T cell differentiation markers and functions in vivo. In this study, we found that synthetic FTS induced appearance of two T cell surface markers, HTLA phenotypes and the ability to form E rosettes, on a selective population of normal human marrow cells sedimenting in layers II or III of a Ficoll discontinuous density gradient. In addition, a population of lymphoid cells also found in layer III, which bears receptors for peanut agglutinin (PNA), was decreased in number following exposure to FTS. In the same gradient layer, cells which expressed terminal deoxyribonucleotidyl transferase (TdT) activity showed decreased activity after treatment with FTS. Functional activities characteristic of T lymphocytes were also enhanced in marrow cells of gradient layer III after preincubation with FTS. These T cell functions were demonstrated in marrow cells by their ability to respond and to stimulate allogeneic peripheral blood lymphocytes (PBL) in mixed lymphocyte reactions and by responses to phytomitogens, PHA, Con A and pokeweed. These changes were not observed in marrow cells of gradient layers I, IV and V or after incubation with an FTS analogue that lacked biological and antigenic activity in the mouse system.

Antigens, Surface↗

Subpopulations of human T lymphocytes. XV. T lymphocytes with receptors for IgA (T alpha), a distinct subpopulation of T lymphocytes. Studies in patients with primary immunodeficiency disorders.

A receptor for IgA was observed on a subset of T cells (T alpha) that is distinct from other T lymphocyte subsets, T mu or T gamma cells. IgA receptor on T alpha cells is blocked by IgA from human serum through its cytophilic attachment. Neither T mu nor T gamma cells, following an in vitro interaction with insoluble immune complexes during the process of purification and further incubation at 37 degrees C, changed their phenotypes to T alpha cells. However, some T gamma cells demonstrated transition to T mu cells. The numbers and proportion of T alpha cells in patients with selective IgA deficiency were either normal, increased or decreased. The significance of T alpha cell analysis in thirty-one patients with primary immunodeficiency disorders including those with selective IgA deficiency is discussed.

Antigen-Antibody Complex↗

Characterization of B-cell leukemias: a tentative immunomorphological scheme.

Analysis of the morphological and immunologic [surface (Sm Ig) and cytoplasmic (Cy Ig) immunoglobulin, faintness (f.imfl) or brightness (b.imfl) of surface immunofluorescence, rosette formation with mouse erythrocytes (MR), or sheep red cells coated with C3 (EAC)] characteristics of the neoplastic lymphocytes involved in 137 cases of B-cell leukemias allowed the differentiation of the following cytologic categories: B1 small lymphocytes (71); SM Ig+, f.imfl., Cy Ig-, MR+, EAC+; B2 prolymphocyte (4): SM Ig+, b.imfl., Cy Ig-, MR+, EAC+. B3 plasmacytoid lymphocyte (2): Sm Ig+, b.imfl., Cy Ig+/-, MR+!-, EAC+/- B4 small cleaved lymphocyte (23): Sm Ig+, b.imfl., Cy Ig-, MR-, EAC+. B5a large cleaved and B5b noncleaved lymphocytes (14): Sm Ig+, b.imfl., Cy Ig-, MR-, EAC-. B6 small noncleaved "Burkitt-like" lymphocyte (5): Sm Ig+, b.imfl., Cy Ig-, MR-, EAC-. B7 plasma cell (2): Sm Ig+, MR-, EAC-. B8 hairy cell (16): Sm Ig+, b.imfl., Cy Ig-, MR-, EAC-, also exhibiting ingestion or attachment of particulate material, not seen in other types. Improved delineation of the heterogeneous group of B-cell leukemias might be of developmental significance in lymphocyte differentiation and improve current prognostic and therapeutic criteria.

Animals↗

Circulating immune complexes, complement and complement component levels in childhood Hodgkin's disease.

Serum levels of circulating immune complexes (CIC) assayed by the Raji cell radioimmunoassay, total haemolytic complement (TCH50), Clq and C3 were correlated with clinical stage, histological type, age, sex and treatment of eighty-six children with Hodgkin's disease over a period of 4 years. Most significant findings were the changes of levels of CIC, TCH50, Clq and C3 during disease activity and following treatment. Significant perturbations were also seen in association with relapse. Levels of C and CIC were significantly elevated (P less than 0.001) at the time of diagnosis prior to splenectomy and/or any treatment. In the group before treatment, 81 percent of CIC levels were above 16 micrograms/ml with a maximum value of 1120 micrograms/ml. During treatment 33 percent were still above normal with a maximum of 320 micrograms/ml. Within 1 year after cessation of treatment, 37 percent also remained above normal levels with a maximum of 240 micrograms/ml. At relapse prior to treatment, 63 percent were again elevated with a maximum of 1280 micrograms/ml. The most significant difference on TCH50 levels relates to treatment periods. Sera of patients with active disease who are previously untreated show elevation of TCH50 levels (P less than 0.001) (average 127 CH50 mu/ml. During and after treatment eht TCH50 levels drop to 96 and 102 CH50 mu/ml, as compared to normal control of 100 CH50 mu/ml. In sera of patients at the first, second or third relapse, the combined TCH50 levels are significantly different from controls and across treatment periods (P less than 0.005).

Adolescent↗

Studies in acute leukemia. II. Chemotaxis of leukemic blasts from patients with acute nonlymphoid leukemia: its relationship with IgG Fc receptors and role of surface-bound immunoglobulin.

Leukemic blasts from patients with acute myeloblastic and acute monocytic leukemia were studied for their chemotaxis towards casein- or endotoxin-activated serum as well as for the presence of Fc receptors and surface immunoglobulins. Leukemic blasts from patients with acute myeloblastic leukemia lacked both Fc receptors and surface immunoglobulin and did not migrate towards chemoattractants. Leukemic blasts from patients with acute monocytic leukemia, however, demonstrated heterogeneity with regard to Fc receptors, surface immunoglobulins and chemotaxis, and could be divided into three groups: in group I, leukemic blasts which lacked both Fc receptors and surface immunoglobulin moved poorly; in group II, large proportions of leukemic blasts and Fc receptors but lacked surface immunoglobulins. These blasts migrated well towards the chemoattractants, and in group III, leukemic blasts which had both Fc receptors and surface immunoglobulins lacked chemotactic property. A correlation between the presence or absence of Fc receptors and chemotaxis was observed. In group III, lack of blast cell migration appears to be due to passive binding of IgG via the Fc receptors.

Acute Disease↗

Circulating immune complexes in sera of dogs with benign and malignant breast disease.

The Raji cell radioimmunoassay was adapted to measure circulating immune complexes (CIC's) in the sera of 74 dogs with benign and malignant breast disease. In dogs with recently diagnosed spontaneous breast cancer, 57% (29 of 51) had elevated CIC's, with some levels as high as those found in the sera of dogs with systemic lupus erythematosus. The sera of 10 of 23 dogs with benign breast disease also demonstrated elevated levels of CIC's. Two weeks following mastectomy, repeat CIC levels were obtained in 30 dogs. Elevated CIC levels returned to normal in all dogs with benign breast disease but in only 33% of dogs with breast cancer. Dogs with persistent elevation of CIC's were at greater risk of developing metastatic breast cancer. Serum total hemolytic complement was significantly higher (p < 0.05) in dogs with untreated breast cancer than in healthy dogs but did not correlate with the level of CIC's found. Two weeks after mastectomy, total hemolytic complement levels had returned to normal. By sucrose density gradient ultracentrifugation, the complexes were shown to sediment at 19 S. These studies indicate that the dog may be a good model for elucidating the significance of elevated CIC's in breast cancer.

Adenocarcinoma↗

Quantitation of circulating immune complexes in serum by Raji cells using an enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) for the quantitation of immune complexes in sera has been developed using Raji cells. In this assay the Raji cell-adherent complexes are detected by an alkaline phosphatase-conjugated rabbit anti-human IgG and the results are obtained by spectrophotometric measurements of the concentration of yellow colour produced after the enzyme's substrate, p-nitrophenyl phosphate, is added. This assay is as sensitive and reproducible as the Raji cell radioimmune assay using 125I, as it can detect as little as 16 micrograms of immune complex equivalent to heat-aggregated IgG/ml in serum samples. This method is inexpensive, convenient and most importantly, avoids the biohazards of using an isotope.

Antigen-Antibody Complex↗