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Biomedical subjects

B F Haynes

Publications and source records attributed to B F Haynes.

At least 217 records · Page 12Linked to original sources
PubMed1983

Effect of thymectomy on peripheral lymphocyte subsets in myasthenia gravis: selective effect on T-cells in patients with thymic atrophy.

Myasthenia gravis (MG) is an autoimmune disease affecting nicotinic acetylcholine receptors. The clinical improvement that follows thymectomy in some myasthenic patients implicates thymic factors as well in the pathogenesis of MG. We have studied circulating immunoregulatory T cell subsets before and after thymectomy in 11 adult patients with MG. Six patients had thymic hyperplasia and five patients had atrophic thymus at the time of thymectomy. Before thymectomy, patients who subsequently were shown to have an atrophic thymus, had lower lymphocyte counts than either patients later shown to have a hyperplastic thymus (1315 +/- 143 lymphocytes/mm3 vs. 2434 +/- 350 lymphocytes/mm3, p less than 0.01), or age-matched controls (1315 +/- 143 lymphocytes/mm3 vs. 2636 +/- 589 lymphocytes/mm3, p less than 0.02). Moreover, after thymectomy, in MG patients with an atrophic thymus, there was a significant rise in lymphocyte count (from 1315 +/- 143 lymphocytes/mm3 to 2279 +/- 292 lymphocytes/mm3, p less than 0.02) beginning 3 days postthymectomy and persisting for at least 6 weeks thereafter. In comparison, patients with a hyperplastic thymus showed no change in circulating lymphocyte counts (p greater than 0.1). Enumeration of lymphocyte subsets in MG patients with an atrophic thymus demonstrated normal B cell numbers before and after thymectomy (p greater than 0.1), whereas, T cells were significantly decreased before thymectomy compared with age-matched normal subjects (859 +/- 82 T cells/mm3 vs. 2215 +/- 545 T cells/mm3, p less than 0.05), and rose to near normal levels after thymectomy (1796 +/- 294 T cells/mm3, p less than 0.02 compared with prethymectomy levels). Using monoclonal anti-T cell antibodies 3A1, OKT4, and OKT8, we found that, before thymectomy in the atrophic thymus group, 3A 1+ T cells were significantly depressed compared with postthymectomy levels (620 +/- 173 cells/mm3 vs. 1627 +/- 331 cells/mm3, p less than 0.02) as were OKT4+ cells 436 +/- 88 cells/mm3 vs. 1112 +/- 63 cells/mm3, p less than 0.001), In contrast, no significant change was seen after thymectomy in the OKT8+ cell subset (p greater than 0.1). MG patients with an atrophic thymus had decreased plasma cortisol levels postthymectomy compared with prethymectomy levels, whereas thymectomy in MG patients with a hyperplastic thymus effected no change in plasma cortisol levels. These data demonstrate in MG patients with an atrophic thymus that thymectomy has an effect on the number of circulating T cells, and in particular, on those T cells expressing antigens 3A1 and OKT4. This effect may in part be mediated by changes in plasma adrenal corticosteroid levels after thymectomy or may be due to a factor produced by atrophic thymuses in MG.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1983

Demonstration of abnormalities in expression of thymic epithelial surface antigens in severe cellular immunodeficiency diseases.

Thymic epithelium from three patients with severe cellular immunodeficiency diseases were compared with age-matched normal thymic epithelium using three markers of human thymic epithelium and antibodies against thymosin alpha 1, thymopoietin, and thymosin beta 4. We have previously shown that normal thymic epithelium reacts with antibodies against GQ gangliosides (antibody A2B5) and binds tetanus toxin (TT). In addition, some areas of normal thymic epithelium express human Thy-1 antigen. We found thymic epithelium in patients with severe cellular immunodeficiency diseases to be different from normal subjects. Two children with severe combined immunodeficiency disease (SCID) had thymic epithelium that bound anti-GQ ganglioside antibody but, unlike in normals, did not bind TT. The patient with severe cellular immunodeficiency and normal serum immunoglobulins (Nezelof syndrome) had thymic epithelium that bound TT but, unlike normal thymic epithelium, did not react with anti-GQ ganglioside antibody. Thymic epithelium from both SCID and Nezelof syndrome patients contained thymosin alpha 1, thymopoietin, and thymosin beta 4 and expressed human Thy-1 antigen. In contrast to SCID thymus rudiments, Nezelof thymus contained numerous (though fewer than normal) lymphocytes with mature T cell surface antigens. Thus, using these probes of human thymic epithelium, we have demonstrated heterogeneous defects in thymic epithelial surface marker expression in severe primary cellular immunodeficiency diseases. These defects presumably reflect abnormalities of in vivo thymic epithelial maturation.

Antibodies, Monoclonal↗
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↗
PubMed1983

Heterogeneity of acute lymphocytic leukemia cell surface markers as detected by monoclonal antibodies.

Monoclonal antibodies 3A1, 4F2, 5E9, OKT3, OKT6, and OKT8 were tested by flow microfluorometry for reactivity with cells from patients with T-cell or null cell acute lymphocytic leukemia (ALL). The 3A1 antibody reacted with a greater percentage of cells from 1 group of patients that could be classified as T-cell leukemia patients as compared to its reaction in the group classifiable as null cell leukemia patients. Reactivity patterns of other monoclonal antibodies with lymphocytes from patients with ALL did not clearly define groups of ALL patients. All cells from individual leukemia patients reacted differently with the seven monoclonal reagents. On the basis of patterns of reactivity, T-cell leukemias could not be classified as malignant clones of cells from the previously described stages of thymus cell maturation. The results demonstrated that the cells undergoing malignant change express a variety of combinations of antigens not found on normal lymphocytes.

Antibodies, Monoclonal↗
PubMed1982

Lymphomatoid Granulomatosis. Prospective clinical and therapeutic experience over 10 years.

Fifteen patients with lymphomatoid granulomatosis were studied prospectively over a 10-year period. Thirteen of the patients received the therapeutic protocol of cyclophosphamide (2 mg per kilogram of body weight per day) and prednisone (1 mg per kilogram on alternate days). Previous reports had indicated that mortality from lymphomatoid granulomatosis was as high as 90 per cent. Of the 13 patients who received the cyclophosphamide and prednisone protocol, seven had complete remissions lasting for 5.2 +/- 0.6 years (mean +/- S.E.M.) Six of the seven with disease in remission have received no therapy for 28.3 +/- 5.7 months. Malignant lymphomas developed in seven of the eight who died, and only two of the eight had therapy for an adequate period. Since virtually all patients who did not have complete remission went on to have malignant lymphoma, early recognition and prompt treatment during the lymphomatoid-granulomatosis phase of disease may not only lead to complete remissions but also percent the development of a lymphoid neoplasm.

Adolescent↗
PubMed1982

Analysis of Fc gamma receptors on human peripheral blood leukocytes by flow microfluorometry. I. Receptor distributions on monocytes, T gamma cells and cells labeled with the 3Al anti-T cell monoclonal antibody.

A dual parameter flow microfluorometric technique for accurately measuring Fc gamma receptor (FcR) expression on defined subsets of cells within a heterogeneous cell sample was developed. The FcR distribution of human peripheral blood mononuclear cells consists of three distinct peaks. By analyzing cells fluorescently labeled with the 3Al, an anti-T cell hybridoma antibody (using a green-emitting fluorophore) and for FcR (with a red-emitting fluorophore), and by using cell isolation procedures, it was shown that the cells lying within the peak with intermediate FcR density are mainly monocytes, while cells lying within the peaks with highest and lowest (i.e. negative) FcR densities are predominantly T cells. The FcR+ T cells (T gamma cells) express higher levels of the 3Al antigen than other T cells, thus demonstrating the utility of the 3Al hybridoma antibody as a marker for T gamma cells.

Antibodies, Monoclonal↗
PubMed1982

Description of monoclonal antibody defining an HLA allotypic determinant that includes specificities within the B5 cross-reacting group.

The selection and characterization of a cloned murine monoclonal antibody (4D12) that defines an HLA allotypic determinant is described. Antibody 4D12 immunoprecipitates HLA heavy and light chains. From studies on 4D12 reactivity with a large panel of well-characterized target cells, antibody 4D12 defines a public HLA determinant that includes specificities within but not identical to the B5 cross-reacting group. Antibody 4D12 should be useful in the study of HLA-B5--related supratypic antigens.

Animals↗
PubMed1982

Differentiation of human T lymphocytes: II. Phenotypic difference in skin and blood malignant T-cells in cutaneous T-cell lymphoma.

The cell surface antigen phenotype of circulating and skin malignant T-cells in patients with cutaneous T-cell lymphoma were studied. The mature T-cell antigen phenotype of the malignant T-cells was identical for circulating and skin malignant T-cells. In contrast, skin malignant T-cells expressed the immature human T-cell antigen Thy-1, surface membrane transferrin receptors, and Ia-like determinants while circulating malignant T-cells did not express these antigens. Skin infiltrating T-cells in benign dermatoses also expressed Thy-1 and Ia-like determinants. These observations support the notion that the skin is a major site of extrathymic T-cell differentiation and may promote phenotypic changes in circulating T-cells that home to skin.

Antigens, Neoplasm↗
PubMed1982

Gamma (immune) interferon production by leukocytes from a patient with a TG cell proliferative disease.

We report a patient with a disease characterized by proliferation of T cells with Fc receptors for IgG (TG). However, unlike lymphoid cells from normal individuals or from patients with other lymphoid malignancies, the patient's lymphocytes spontaneously produced gamma interferon (IFN-gamma) in vitro. The peripheral lymphocytes consisted of 95% TG cells, which exhibited the morphological characteristics of T-cell chronic lymphocytic leukemia (CLL) and were normal on cytochemical and chromosome analysis. The majority of TG cells were OKT3+, OKT8+, and OKT4-, 3A1-. These cells failed to express suppressor cell activity and displayed depressed levels of natural killer activity, but mediated antibody-dependent cell-mediated cytotoxicity. The spontaneous production of IFN-gamma by human peripheral lymphoid cells as demonstrated in this study may serve as a probe for studying the relationship between IFN-gamma and the proliferation of human T-cell subsets.

Cells, Cultured↗
PubMed1982

Phenotypic characterization of skin-infiltrating T cells in cutaneous T-cell lymphoma: comparison with benign cutaneous T-cell infiltrates.

Using a panel of monoclonal antibodies, we have studied cell surface antigens of infiltrating mononuclear cells in skin biopsies from patients with cutaneous T-cell lymphoma (CTCL) and compared them with the T-cell surface phenotype seen in benign cutaneous T-cell infiltrations (e.g., contact dermatitis, delayed hypersensitivity skin tests, granuloma annulare) and in dermal infiltrates of lymphomatoid granulomatosis patients. We found that unlike circulating CTCL (Sézary) cells, CTCL cells infiltrating skin epidermis frequently expressed the T-cell antigen 3A1. Cutaneous infiltrates in 10 patients with mycosis fungoides (MF) and 1 patient with Sézary syndrome were OKT4 (inducer T cell), OKT8 (suppressor/cytotoxic T cell); 2 patients with MF were OKT4-, OKT8; and one MF patients's skin T cell were OKT4-, OKT8+. Similar to CTCL infiltrating cells, most of the benign skin T-cell infiltrates were usually 3A1+. OKT4+, and OKT8-. Our study shows the complex nature of T-cell antigen patterns in inflammatory and malignant skin T-cell infiltrations. We demonstrated that the CTCL the skin epidermal infiltrating T-cell phenotype is not invariate, and in many cases, is similar to the phenotype of clinically benign cutaneous T-cell infiltrations.

Antibodies, Monoclonal↗
PubMed1981

Phenotypic characterization of cutaneous T-cell lymphoma. Use of monoclonal antibodies to compare with other malignant T cells.

We studied the surface-antigen pattern of T cells in peripheral blood and cell lines from patients with advanced cutaneous T-cell lymphoma (CTCL) or T-cell acute lymphoblastic leukemia. The antigen patterns of cutaneous T-cell lymphoma cells from peripheral blood and established cell lines were nearly identical; the cells were negative for human thymus antigen (OKT6 and NA1/34), positive for pan-T-cell (OKT3, 17F12, 10.2, and 9.6) and helper-T-cell-subset (OKT4) antigens, and negative for T-cell-subset antigens 3A1 and OKT8. In contrast, the phenotypes of malignant T cells from patients with acute lymphoblastic leukemia were heterogeneous, with at least five patterns of reactivity. The T-cell-specific antibody 3A1 was the only monoclonal reagent that clearly distinguished the peripheral-blood T cells in CTCL (3A1-) from those in acute lymphoblastic leukemia (3A1+). Moreover, 3A1 was the most reliable T-cell marker in acute lymphoblastic leukemia. We conclude that circulating CTCL (Sézary) T cells are homogeneous in their antigen phenotype and are derived from a well-differentiated 3A1-, OKT4+, OKT8- helper-T-cell subset.

Adult↗
PubMed1981

Phenotypic characterization of human cytolytic T lymphocytes in mixed lymphocyte culture.

Mixed lymphocyte reaction (MLR)-activated T cells were analyzed according to the expression of various cell surface markers by the specific cytotoxic T lymphocytes (CTL) generated in the MLR. CTL were found exclusively in a population of MLR-activated T cells that lacked detectable Fc gamma R but that expressed a surface antigen recognized by the 4F2 monoclonal antibody. In contrast, CTL were found in both the Ia-positive and Ia-negative cells after MLR activation. Thus, the specific CTL generated in the allogeneic MLR can be identified and isolated by virtue of the expression of a particular cell surface marker.

Antigens, Surface↗
PubMed1981

Successful treatment of sudden hearing loss in Cogan's syndrome with corticosteroids.

Cogan's syndrome (CS) is the association of acute nonsyphilitic interstitial keratitis and acute episodes of vertigo, tinnitus, and hearing loss. We have prospectively followed 6 patients with CS who were treated within 4 weeks after the acute onset of hearing loss. Within 1 to 2 weeks after the initiation of corticosteroid therapy, all 6 patients demonstrated improved hearing thresholds for pure tones and supra-threshold speech discrimination results. These patients have been followed an average of 2.5 years (range 0.25-9 years); all have only mild to moderate hearing impairment in the mid (1,000 to 2,000 Hz) and low (250 to 500 Hz) frequency sound ranges. Three of the patients have been tapered off steroids completely with no subsequent permanent decrement of hearing. Thus, early oral corticosteroid administration to patients with sudden hearing loss associated with Cogan's syndrome may preserve auditory function.

Acute Disease↗
PubMed1981

Cell surface differentiation antigens of the malignant T cell in Sezary syndrome and mycosis fungoides.

Using a panel of monoclonal antibodies and rabbit heteroantisera, we have studied the cell surface markers of peripheral blood (PB) Sezary cells from six patients with mycosis fungoides or Sezary syndrome, disease grouped within the spectrum of cutaneous T cell lymphomas (CTCL). Furthermore, we have studied two cell lines (Hut 78 and Hut 102) derived from malignant Sezary T cells from CTCL patients. The monoclonal antibody 3A1 defines a major human PB T cell subset (85% of PB T cells) while the antigen defined by the monoclonal antibody 4F2 is present on a subset (70%) of activated PB T cells and on circulating PB monocytes. In contrast to normal subjects in whom 60-70% of circulating PB mononuclear cells were 3A1(+) T cells, PB mononuclear cells from six CTCL patients studied had an average of only 10.6+/-3.2% 3A1(+) T cells. Whereas 85% of E-rosette positive cells from normal individuals were 3A1(+), virtually all E-rosette positive T cells from the Sezary patients were 3A1(-). Two patients with high numbers of circulating Sezary T cells had both aneuploid and diploid PB T cell populations present; after separation of PB T cells into 3A1(+) and 3A1(-) cell suspensions, all 3A1(-) cells were found to be aneuploid. In contrast to normal resting PB T cells which were 4F2(-), all PB Sezary cells were 4F2(+), suggesting a state of activation. The 3A1 antigen was on a variety of acute lymphoblastic leukemia T cell lines (HSB-2, RPMI-8402, MOLT4, CEM) but was absent on the Hut 78 and Hut 102 Sezary T cell lines. Using rabbit anti-human T and anti-human Ia (p23, 30) antisera, we found that all malignant Sezary PB cells tested were killed by anti-T cell antiserum plus complement but not by anti-Ia plus complement. In contrast, Sezary cell lines Hut 78 and 102, were killed by both anti-T cell antiserum and anti-Ia plus complement. Similar to 3A1(-) normal PB T cells, 3A1(-) Sezary PB T cells proliferated poorly to phytohemagglutinin and concanavalin A. However, 3A1(-) Sezary T cells were able to provide T cell help towards pokeweed mitogen-induced in vitro B cell immunoglobulin synthesis, an immunoregulatory function limited to 3A1(+) T cells in normal subjects.Thus, the 3A1 antigen is present on 85% of normal PB T cells, and on most T-acute lymphoblastic leukemia lines tested; in contrast the 3A1 antigen is not present on the majority of circulating malignant Sezary PB T cells nor on T cell lines derived from malignant Sezary T cells. The lack of expression of the 3A1 antigen may be associated with malignant transformation of T cells in CTCL and may be an important marker for tracing the clonal origin of the malignant Sezary T cell.

Adult↗