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Biomedical subjects

S Broder

Publications and source records attributed to S Broder.

At least 199 records · Page 11Linked to original sources
PubMed1983

Inhibitory activity of antibodies to human Ia-like determinants: comparison of intact and pepsin-digested antibodies.

Antibodies which react with products encoded by the human DR locus precipitate a biomolecular membrane glycoprotein complex with m.w. of 29,000 and 34,000 daltons. Such antibodies are directed against HLA-DR Ia-like antigens found on human B cells and human monocytes and have been shown previously to inhibit a variety of in vitro cellular and humoral immune reactions. We have compared the in vitro effects of such antibodies on two assays of human immunity: antigen-specific proliferation and polyclonal immunoglobulin production. Intact IgG fractions of a rabbit heteroantiserum (anti-P29,34), a human MT-2 locus alloantiserum (Ia 172), and a mouse monoclonal antibody (LB 3.1) markedly inhibited in vitro immune reactivities of human mononuclear cells. Interestingly, F(ab')2 preparations of these antibodies failed to inhibit these in vitro immune responses at the concentrations tested. These data suggest that under certain conditions, Fc domains play a critical role in the inhibitory activity of antibodies to Ia-like molecules.

Animals↗
PubMed1983

Association of the human type C retrovirus with a subset of adult T-cell cancers.

To determine whether the human T-cell lymphoma-leukemia virus (HTLV) is associated with particular cancers, patient sera were surveyed for HTLV-specific antibodies. An association was seen with aggressive cancers of mature T-cells, specifically Japanese adult T-cell leukemia (ATL) and T-cell lymphosarcoma cell leukemia (TLCL), a similar cancer of Caribbean blacks. Ninety to 100% of these patients possessed HTLV-specific antibody. Forty-seven and 20% of relatives of ATL and TLCL patients, respectively, and 12 and 4% of healthy donors from ATL and TLCL endemic areas were also antibody positive. Visceral organ involvement, hypercalcemia, and skin manifestation, features of ATL and TLCL, were often seen in other antibody-positive patients. Childhood cancers, most cutaneous T-cell and all non-T-cell leukemias and lymphomas, myeloid leukemias, Hodgkin's disease, and solid tumors were not associated with HTLV. Healthy United States donors and European patients with non-malignant diseases were antibody negative. HTLV is thus associated with a subtype of adult T-cell leukemia-lymphoma, clustered in viral endemic areas, with apparent racial and geographic predilection.

Adult↗
PubMed1982

Human T-cell leukemia-lymphoma virus (HTLV) is in T but not B lymphocytes from a patient with cutaneous T-cell lymphoma.

A human type C retrovirus, designated HTLV, previously was isolated from or identified in some patients with leukemias and lymphomas of mature T lymphocytes. HTLV is genetically and serologically distinct from any known animal retroviruses. The absence of HTLV proviral sequences in DNA from normal humans showed that HTLV is not a ubiquitous endogenous (germ-line transmitted) virus of humans. Antibodies to HTLV core proteins have been identified in some people with T-cell neoplasias and are particularly prevalent in Japanese with adult T-cell leukemia, suggesting that HTLV is acquired horizontally. However, it was possible that HTLV is transmitted through the germ line of some (possibly rare) families and is then expressed in the HTLV- positive malignancies. An opportunity to study this question was provided by the development of several T-cell lines and a B-cell provided by the development of several T-cell lines and a B-cell line from one HTLV-positive patient with a cutaneous T-cell lymphoma. Here we report that HTLV proteins or nucleic acids (or both) are found in three independently derived T-cell lines, all shown by HLA typing to have originated from the patient. In contrast, the B-cell line, the identity of which was also ascertained by HLA typing, contained no detectable HTLV protein, RNA, or proviral DNA. Because the sensitivity of the latter assay is more than sufficient to detect one proviral equivalent per haploid genome, the results indicate that HTLV was not transmitted to this patient through the germ line but rather was acquired by infection.

B-Lymphocytes↗
PubMed1982

Chemotherapy for lymphoma in a patient with common variable immunodeficiency: case report, literature review, and recommendations for chemotherapy in immunodeficient patients.

A man with long-standing common variable hypogammaglobulinemia was treated with chemotherapy and local radiation for diffuse mixed lymphoma. He continues in complete remission 42 months after the completion of therapy. Vigorous therapy for lymphoma can be used in the face of preexistent immunodeficiency. Complete staging and appropriate combination chemotherapy or radiation therapy should be carried out for lymphomas that occur in certain immunodeficient patients.

Adult↗
PubMed1981

Activation of leukemic pro-suppressor cells to become suppressor-effector cells. Influence of cooperating normal T cells.

We studied the suppressor activity and surface-membrane antigens of immunoregulatory neoplastic T cells from a child with acute lymphoblastic leukemia and hypogammaglobulinemia. The neoplastic T cells were potent inhibitors of immunoglobulin production by pokeweed-mitogen-stimulated normal B cells when radiosensitive cooperative normal T cells were present. Preculturing the leukemic cells with normal T cells or soluble factors allowed them to mediate suppression without the need for cooperating T cells. While acquiring new functional capabilities, approximately 95 per cent of the leukemic cells displayed an antigen (OKT-3) that is found on mature normal T cells; 77 per cent displayed an antigen (Tac) that is found on normal activated immunoregulatory effector cells but not on thymocytes or circulating T cells that are precursors of these effector cells. The results suggest that a population of leukemic prosuppressor cells can be induced to undergo both functional and antigenic differentiation by the influence of normal T cells.

Agammaglobulinemia↗
PubMed1981

Metabolic heterogeneity of eosinophils from normal and hypereosinophilic patients.

Eosinophils, which may be associated with allergic, parasitic, or neoplastic disease, have a potent oxidative burst that may be activated by particulate or soluble stimuli. Eosinophils from normal persons and patients with hypereosinophilia were compared with respect to their ability to produce the active oxygen product, superoxide anion. Normal eosinophils produced large amounts of superoxide anion under resting conditions (0.53 +/- 0.15 nmoles cyto-c/10(5) eos/hr) and when stimulated by preopsonized zymosan (0.85 +/0 1.10 nmoles cyto-c/10(5) eos/hr) or phorbol myristate acetate (PMA) (2.38 +/- 0.46 nmoles cyto-c/10(5) eos/hr). Considerable variation was observed in superoxide production by eosinophils from patients with hypereosinophilia. Eosinophils from a group of four patients with hypereosinophilia associated with neoplastic disease produced less superoxide anion than normal eosinophils when stimulated by preopsonized zymosan or PMA (p less than or equal to 0.05). Eosinophils from a group of 5 patients with other causes of hypereosinophilia produced more superoxide anion than normal eosinophils when stimulated by PMA (p less than or equal to 0.01). These studies demonstrate metabolic heterogeneity of eosinophils from patients with hypereosinophilia, and further emphasize that normal eosinophils and eosinophils from hypereosinophilic patients are not functionally equivalent.

Eosinophilia↗
PubMed1981

Homologous artificial insemination after long-term semen cryopreservation.

Although there are sporadic reports of pregnancies using semen after long-term cryopreservation, there are no data on the success rate of this procedure and its clinical feasibility. Between 1969 and 1980, 475 men deposited semen specimens prior to vasectomy or therapeutic sterilization. Prefreeze sperm counts and motility were significantly higher in the prevasectomy group. Later, 5 wives of 177 vasectomized men and 16 wives of 183 therapeutically sterilized men returned for artificial insemination with their husbands' semen. Only 1 conception resulted among the 21 women. This occurred after a single insemination of a 7-year-old specimen obtained prevasectomy. The post-thaw motility of this specimen (45%) was better than that of most other thawed specimens. Post-thaw motilities were unpredictable despite comparable prefreeze motilities. Because of this unpredictability, semen cryopreservation is clearly no guarantee of "fertility insurance".

Female↗
PubMed1981

Resolution of longstanding protein-losing enteropathy in a patient with intestinal lymphangiectasia after treatment for malignant lymphoma.

In 1956 we evaluated a patient who had a debilitating disease of a 2 yr duration, characterized by recurrent vomiting, diarrhea, cachexia, massive edema, hypoproteinemia, and dilated intestinal lymphatics. During our initial evaluation of this patient, we observed that 42% of her circulating protein pool was lost into her gastrointestinal tract daily, whereas normal gastrointesinal loss of protein does not exceed 1.6%. Her disease appeared to represent a classic example of intestinal lymphangiectasia. She was treated symptomatically for 13 yr with essentially no change. In 1969 the patient developed a stage IV diffuse, undifferentiated (non-Burkitt's) malignant lymphoma. Using immunoperoxidase staining, the neoplastic cells were found to contain cytoplasmic IgMKappa, suggesting that the lymphoma had a monoclonal B-cell origin. She was successfully treated with cyclophosphamide, vincristine, and prednisone. Shortly after the initiation of this systemic combination chemotherapy, her serum protein concentration returned to normal, her edema resolved, and she was cured of gastrointestinal symptoms. Moreover, repeat studies revealed that her protein loss had fallen to only 2%. The simultaneous cure of both the intestinal lymphangiectasia and lymphoma with combination chemotherapy suggests new relationships between these conditions as well as new possibilities for the treatment of acquired forms of intestinal lymphangiectasis associated with overwhelming gastrointestinal protein loss.

Adult↗
PubMed1980

X-linked hypogammaglobulinemia and isolated growth hormone deficiency.

We undertook clinical, immunologic, and endocrinologic studies of a family in which two brothers and their two maternal uncles had a similar disorder characterized by hypogammaglobulinemia and isolated growth hormone deficiency. Recurrent sinopulmonary infections were a prominent feature in two patients. All patients had short stature and retarded bone age during childhood, and the adults had delayed onset of puberty. The immunodeficiency was characterized by absent specific antibody production in vivo and impaired immunoglobulin production in vitro. Three of the four patients lacked circulating B lymphocytes, even though tonsils were present in those patients. All patients had deficient growth hormone responses to insulin and arginine or levodopa. These patients have an X-linked recessive disorder, but their immunodeficiency differs from the X-linked immune disorders in the World Health Organization classification; their X-linked pattern of growth hormone deficiency, without other endocrine abnormality, is also unique.

Adolescent↗
PubMed1980

Participation of suppressor T cells in the immunosuppressive activity of a heteroantiserum to human Ia-like antigens (p23,30).

We studied the effects of an antiserum to human Ia-like antigens (p23,30) upon the polyclonal activation of normal B cells (cultured with various combination of irradiated and unirradiated T cells) to become immunoglobulin-secreting cells after stimulation with pokeweed mitogen in vitro. We found that the antiserum suppressed immunoglobulin production. The inhibitory effect did not appear to result from a simple interaction at the B-cell/monocyte level alone. Rather, the inhibitory effect required the presence of a radiosensitive subset of autologous suppressor T cells.

Animals↗
PubMed1980

High molecular weight antigens present on human T cells.

A series of eight high molecular weight (140,000-220,000) glycoproteins on human peripheral T cells were recognized by radioimmunoprecipitation with a rabbit antiserum. The pattern of antigens present on each of eight human T cell lines studied was unique, and no line displayed the range of antigens present on peripheral T cells. The pattern of bands on peripheral T cells changed after allogeneic or lectin stimulation. Adsorption/elution experiments with antiserum showed that some of these proteins were antigenically related, and at least three different groups of proteins were present. Two of these groups could be partially distinguished by their ability to bind to ricin or lentil lectin and by their reactivity with two additional rabbit antisera. On some cell lines, it was found that proteins bound by lentil lectin but not ricin were precursors of higher molecular weight material recognized by ricin. Taken together, the data suggest that these proteins may be the products of a multigenic or multiallelic system, probably equivalent to the murine Ly 5 antigens.

Antigens, Surface↗
PubMed1980

Neoplasms of immunoregulatory T cells in clinical investigation.

Normal T cells play a critical role in the regulation of humoral immune responses by acting as potentiators (helper cells) or inhibitors (suppressor cells) of the process by which B cells differentiate into immunoglobulin-secreting plasma cells. Certain diseases in which malignant T cells appear to retain an immunoregulatory function are characterized by a propensity of a lymphomatous T-cell population to infiltrate skin. Some cutaneous T-cell lymphomas, as well as some T-cell neoplasms without dermatologic involvement, provide a homogeneous supply of T lymphocytes which act as immunoregulators. The availability of neoplastic T cells with immunoregulatory properties could accelerate the serologic and biochemical analysis of the cellular control of normal immunity in man.

Agammaglobulinemia↗
PubMed1980

Immunoregulatory functions of cultured human T lymphocytes.

Twenty continuous cultures of human T cells (CTC) (15 from normal individuals and five from patients with T cell malignancy) growing in the presence of PHA-stimulated lymphocyte conditioned medium were studied for their ability to participate in the regulation of the in vitro immunoglobulin (Ig) production induced by five polyclonal activators, pokeweed mitogen (PWM), Epstein-Barr virus (EBV), Nocardia opaca water-soluble mitogen (NWSM), streptolysin O (SLO), and staphylococcl phage lysate (SPL). The CTC did not produce significant amounts of Ig in the presence of any polyclonal activator. One out of 15 CTC examined showed helper activity of moderate degree when co-cultured with B cells rigorously depleted of T cells in PWM-driven Ig biosynthesis. Two of the other CTC helped minimally. Nine of 20 CTC examined (8 of 15 from normal individuals and 1 of 5 from patients with T cell malignancies) were found to have marked suppressor cell activity when co-cultured with normal lymphocytes in the PWM-induced Ig production system and four had moderate or variable suppressive effect. This suppression was apparently not due to simple "overgrowth" or nonspecific toxic effects of CTC because (1) the CTC did not proliferate when cultured without conditioned medium, (2) the CTC did not suppress Ig production when they were added 3 days after the beginning of the 12-day cultures, (3) the CTC did not show cytotoxic activity against normal T and B cells, and (4) the CTC did not inhibit tritiated thymidine incorporation into PWM- or EBV-stimulated lymphocytes when mixed with them at the onset of culture. Ig production induced by EBV or NWSM, which are relatively T cell-independent polyclonal activators, was suppressed significantly T cell-independent polyclonal activators, was suppressed significantly by only one out of nine and one out of six CTC examined, respectively. Four clones produced by a limiting dilution method from one suppressor CTC suppressed PWM-driven Ig synthesis as markedly as the uncloned suppressor CTC. Such CTC may be of considerable value in studies of the mechanisms involved in the regulation of immunoglobulin biosynthesis and in the preparation of antisera to T cell subsets.

B-Lymphocytes↗