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Biomedical subjects

S Broder

Publications and source records attributed to S Broder.

At least 235 records · Page 13Linked to original sources
PubMed1977

The metabolism of IgE in patients with immunodeficiency states and neoplastic conditions.

Serum IgE concentrations were determined and IgE turnover studies were performed in control individuals as well as in patients with several disease states. Patients with common variable hypogammaglobulinemia, thymoma and hypogammaglobulinemia, ataxia telangiectasia, and selective IgA deficiency had significantly decreased mean serum IgE concentrations. In turnover studies, this was found to be due to decreased IgE synthesis. In spite of these depressed mean values, some patients with common variable hypogammaglobulinemia had normal serum IgE concentrations and synthetic rates. Patients with the Wiskott-Aldrich syndrome had a significantly elevated mean serum IgE concentration. In one of four patients studied with the turnover technique, a strikingly high IgE concentration was present and was associated with an elevated IgE synthetic rate. Three other patients had both normal serum IgE concentrations and synthetic rates. Patients with chronic lymphocytic leukemia had significantly decreased mean serum concentrations and synthetic rates for IgE. The depressed IgE synthesis was associated with a significantly prolonged IgE half-life. Patients with Hodgkin's disease had significantly increased serum IgE concentrations. One of three patients studied had a high serum IgE concentration and synthetic rate of IgE. The two other patients had normal serum IgE concentrations associated with normal synthetic rates. Finally patients with protein-losing enteropathy or familial hypercatabolic hypoproteinemia had normal IgE concentrations associated with normal IgE metabolic parameters. In these cases, the disorder in the catabolic rate was not severe enough to affect the total amount of circulating IgE because IgE normally has a very high fractional catabolic rate. In general, IgE levels in a variety of disease states were correlated with IgE synthetic rates and abnormalities in the catabolic rate of IgE in disease did not exert an important effect on IgE concentration.

Adolescent↗
PubMed1976

Unusual clonal evolution in a case of chronic myelogenous leukemia.

Several unusual cytogenetic changes have occurred during the evolution of chronic myelogenous leukemia in a 32-year-old white male with this disease for 8 years. The first appearance of a hypodiploid cell line containing a dicentric marker occurred 2 years after diagnosis and this line was eliminated by several courses of therapy with hydroxyurea. A second clone, which had a partial deletion of the long arm of one of the number 8 chromosomes (8q-) was noted a year later, but this line has been refractory to intensive combination chemotherapy.

Adult↗
PubMed1976

The Sézary syndrome: a malignant proliferation of helper T cells.

The Sézary syndrome is a frequently lethal disease characterized by circulating malignant cells of thymus-derived (T)-cell origin. The capacity of circulating malignant lymphocytes from patients with this syndrome to synthesize immunoglobulins and to function as helper or suppressor cells regulating immunoglobulin synthesis by bone marrow-derived (B) lymphocytes was determined. Peripheral blood lymphocytes from normal individuals had geometric mean immunoglobulin synthetic rates of 4,910 ng for IgM, 1,270 ng for IgA, and 1,625 ng for IgG per 2 X 10(6) cells in culture with pokeweed mitogen for 7 days. Purified normal B cells had geometric mean synthetic rates of 198 ng for IgM, 145 ng for IgA, and 102 ng for IgG. Leukemic cells from patients with the Sézary syndrome produced essentially no immunoglobulins. Adding normal T cells to normal B cells restored their immunoglobin producing capacity. Leukemic cells from four of five patients tested had a similar capacity to help immunoglobulin synthesis by purified normal B cells. Additionally, Sézary cells from one patient studied induced a nearly 10-fold increase in IgA synthesis by lymphocytes from a child with ataxia telangiectasia and selective IgA deficiency. Furthermore, these Sézary cells induced more than a 500-fold increase in IgG and IgA synthesis by lymphocytes from a child with Nezelof's syndrome. When Sézary cells were added to normal unfractionated lymphocytes, they did not suppress immunoglobulin biosynthesis. In addition, unlike the situation observed when large numbers of normal T cells were added to purified B cells, there was no depression of immunoglobulin synthesis at very high malignant T-cell to B-cell ratios. These data support the view that Sézary T cells do not express suppressor cell activity. The results presented in this paper suggest that neoplastic lymphocytes from the majority of patients with the Sézary syndrome originate from a subset of T cells programmed exclusively for helper-like interactions with B cells in their production of immunoglobulin molecules.

Adult↗
PubMed1976

Familial chronic lymphocytic leukemia. Immunologic and cellular characterization.

Chronic lymphocytic leukemia developed in four of five siblings, whose father succumbed to the same disease. The pattern of immune deficiency in the leukemic siblings resembled that found in nonfamilial cases of chronic lymphocytic leukemia, and was correlated with the severity of clinical involvement. In three siblings the peripheral blood leukemic cells shared delta-heavy and kappa-light chains as the only detectable surface immunoglobulin, suggesting that on a cellular and molecular level the chronic lymphocytic leukemia in family members is identical. The fourth and youngest sibling had no peripheral blood lymphocytes with detectable surface immunoglobulin. An inherited defect in the class of cells destined to express delta-heavy and kappa-light chains appears to underlie susceptibility to leukemia in this family.

Aged↗
PubMed1976

The role of suppressor cells in the pathogenesis of common variable hypogammaglobulinemia and the immunodeficiency associated with myeloma.

The role of suppressor cells in the pathogenesis of immunodeficiency was analyzed using a technique that permits study of the differentiation of B lymphocytes into immunoglobulin-synthesizing plasma cells. Lymphocytes from normals synthesized 4,910 ng of IgM, 1,270 ng of IgA, and 1,625 ng of IgG per 2 X 10(6) cells when cultured for 7 days in the presence of pokeweed mitogen. In contrast the lymphocytes from patients with common variable hypogammaglobulinemia did not synthesize significant quantities of immunoglobulin. When lymphocytes from 9 of 13 patients with common variable hypogammaglobulinemia studied were cocultured with normal lymphocytes, the synthesis of immunoglobulin by the normal lymphocytes was depressed by 75-100%. A comparable suppression of immunoglobulin synthesis by normal lymphocytes was observed when they were cocultured with T cells from hypogammaglobulinemic patients. These studies suggest that in some patients the disease common variable hypogammaglobulinemia may not be due to an intrinsic defect of B cells alone but may be cuased or perpetuated by an abnormality of regulatory T cells that act to suppress B-cell maturation and antibody production. Peripheral blood lymphocytes from myeloma patients also had a drastically reduced capacity to produce polyclonal immunoglobulins. Three of 6 myeloma patients tested had circulating mononuclear cells that suppressed immunoglobulin production by cocultured normal lymphocytes. Purified T cells from myeloma patients did not mediate this suppressor effect. These observations suggest that one mechanism for the humoral immune deficiency observed in myeloma patients is a block of polyclonal B-cell maturation by suppressor cells.

Agammaglobulinemia↗
PubMed1976

Defect in IgA secretion and in IgA specific suppressor cells in patients with selective IgA deficiency.

The nature of the defect in patients with selective IgA deficiency was investigated using a technique established to study terminal differentiation of B lymphocytes into immunoglobulin synthesizing and secreting cells. The peripheral blood lymphocytes from normal individuals had geometric mean synthetic rates of 4910 ng for IgM, 1625 ng for IgG and 1270 ng for IgA per 2 x 10(6) cells in culture for 7 days in the presence of pokeweed mitogen. The cultured lymphocytes from each of the 14 patients with selective IgA deficiency studied synthesized normal quantities of IgG and IgM but secreted less than 100 ng of IgA into the media. However, 11 of the 14 patients studied synthesized IgA by the 7th day in PWM stimulated cultures as assessed by staining for cytoplasmic IgA using fluorescein-labeled anti-IgA antisera. Synthesis and secretion of IgA by normal cells was not suppressed when they were co-cultured with lymphocytes from these patients that synthesize but do not secrete IgA. Three of the 14 patients did not have lymphocytes with IgA demonstrable in their cytoplasm following culture. When the lymphocytes from these 3 patients were co-cultured with normal lymphocytes and pokeweed mitogen the synthesis of IgA by the normal cells was depressed by 80 to 100%. Synthesis of IgG and IgM was not depressed. These studies suggest that lymphocytes cultured with pokeweed mitogen from the majority of patients with selective IgA deficiency can synthesize IgA but have a defect in IgA secretion. A smaller group of the patients do not synthesize IgA and have IgA specific suppressor cells that prevent B cells from maturing into IgA synthesizing and secreting cells.

Adolescent↗
PubMed1975

Impaired synthesis of polyclonal (non-paraprotein) immunoglobulins by circulating lymphocytes from patients with multiple myeloma Role of suppressor cells.

Since patients with myeloma have serious abnormalities of humoral immunity, we applied an in vitro assay to determine the capacity of B lymphocytes to mature into immunoglobulin-secreting cells. In peripheral blood lymphocytes from 22 normal persons, geometric mean immunoglobulin synthesis was 4910 ng for IgM, 1270 ng for IgA and 1625 ng for IgG. The synthesis rates of peripheral blood lymphocytes of 22 patients with myeloma were 458 ng for IgM, 321 ng for IgA and 218 ng for IgG. Circulating mononuclear cells from three of six patients tested suppressed polyclonal immunoglobulin synthesis by cocultured normal lymphocytes. Suppressive activity was not mediated by purified T cells alone. Removal of phagocytic mononuclear cells from lymphocyte populations of one patient nullified suppressive activity. Removal of phagocytic mononuclear cells from lymphocyte populations of a second patient led to a nearly 10-fold increase in polyclonal immunoglobulin synthesis. Therefore, host suppressor cells may play a part in the decreased capacity of B lymphocytes to secret immunoglobulin in certain patients with myeloma.

Adolescent↗
PubMed1975

Suppressor T cells in the pathogenesis of hypogammaglobulinemia associated with a thymoma.

The nature of the immunological defect in patients with hypogammaglobulinemia associated with a thymoma was investigated using a technique established to study the differentiation of lymphocytes into immunoglobulin synthesizing and secreting cells. Exhaustively washed peripheral blood lymphocytes were cultured for 7 days in RPMI-1640 medium supplemented with fetal calf serum in the presence of the lectin, pokeweed mitogen. The IgG, IgA, and IgM synthesized and secreted into the medium were measured by competitive double antibody radio-immunoassays. Twenty-two normal individuals synthesized 1625 ng of IgG, 1270 ng of IgA, and 4910 ng of IgM per 2 million lymphocytes in culture. In contrast, the three patients with hypogammaglobulinemia and a thymoma synthesized less than 100 ng of each class of immunoglobulin. When lymphocytes from 2 of the 3 patients studied were cocultured with normal lymphocytes and pokeweed mitogen, the synthesis of immunoglobulin by normal lymphocytes was depressed by a factor of 66 to 97%. Co-cultue of purified T cells from the hypogammaglobulinemic patients with normal lymphocytes resulted in an 87% suppression of immunoglobulin synthesis by the normal cells. However, no suppression of immunoglobulin synthesis was observed when preparations of B cells and macrophages depleted of T cells from the hypogammaglobulinemic patients were co-cultured with normal lymphocytes. In addition, in control studies no such suppression of immunoglobulin synthesis was seen when normal cells were co-cultured with lymphocytes from unrelated normals, patients with isolated IgA deficiency, patients with chronic lymphocytic leukemia or patients with the Sezary syndrome, a T cell leukemia nor were they inhibited when incubated with T cells from unrelated normals. These observations suggest that in some patients the hypogammaglobulinemia associated with a thymoma may be caused or perpetuated by an abnormality of regulatory T cells which suppress the maturation of lymphocytes into antibody producing cells.

Adolescent↗