Perforation of an unsuspected cecal granulocytic sarcoma during therapy with granulocyte-macrophage colony-stimulating factor.
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Aged↗
Biomedical subjects
A Winkelstein
Publications and source records attributed to A Winkelstein.
Multicentric reticulohistiocytosis and Sjögren's syndrome.
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Aged↗
Interleukin-2-induced lymphoproliferative responses.
Interleukin-2 (IL-2) is capable of both stimulating an in vitro lymphoproliferative response and augmenting non-major-histocompatibility-complex-(MHC)-restricted cytotoxicity. However, there are conflicting reports about the phenotypes of responding cells. In the present studies, we determined phenotypes of Ficoll/Hypaque-separated peripheral blood mononuclear cells stimulated with 50, 100 or 1000 U/ml IL-2; analyses were performed after 1, 3 and 5 weeks. With all concentrations, there was a progressive increase in CD3+ cells: after 3-5 weeks more than 90% of the cells reacted with this antibody. However, the proportions of CD4+ and CD8+ cells proved to be a function of the IL-2 concentration. Cultures containing 50 U/ml or 100 U/ml favored the expansion of the CD4+ subset. By contrast, in cultures stimulated with 1000 U/ml. CD8+ cells predominated. At baseline, CD8+ cells comprised 28 +/- 2%; after 3 weeks, this value increased to 51 +/- 5%. In addition, the proportion of CD56+ (Leu19, NKH-1) cells depended on the amount of IL-2. At 50 U/ml, there was no appreciable change in CD56+ cells. However, at 1000 U/ml, CD56+ cells increased from 17 +/- 1% (day 0) to 39 +/- 4% (3 weeks). This increase was primarily due to an expansion of the CD3+ CD56+ subset (non-NMC restricted cytotoxic T cells). By contrast, natural killer (NK) cells, as measured by the CD16 antibody, steadily declined at all IL-2 concentrations.
Antibodies, Monoclonal↗
Recurrence of adult Still's disease after pregnancy.
A 35-year-old white woman had recurrent episodes of adult onset Still's disease after 2 successive pregnancies. The second episode was characterized by an erythematous, macular rash, arthritis, fevers and hepatic dysfunction which occurred 2 months postpartum. The recurrent illness after pregnancy suggests that adult onset Still's disease may be influenced by gestational status.
Adult↗
Chimerism studies using in situ hybridization for the Y chromosome after T cell-depleted bone marrow transplantation.
In situ hybridization for the Y chromosome (Y-ISH) was used to monitor engraftment in 10 patients with hematological malignancies who had received T cell-depleted marrow transplants from sex-mismatched donors, seven of whom were only partially HLA-matched. In the three patients who engrafted, as the peripheral counts rose, the percentage of host peripheral blood and marrow mononuclear cells decreased steadily, although host cells (less than 1%) could still be detected as late as day 252. The percentage of host granulocytes fell rapidly to less than 0.2%. Seven patients did not achieve full engraftment by day 28. Those with a low percentage of host cells (less than 1%) improved with observation or treatment with steroids, while those with a high or increasing percentage of host cells did not improve even after treatment with GM-CSF or with repeat marrow infusion without reconditioning. In one patient with graft failure, the residual host cells were predominantly CD8+ CD57+ and CD3+ CD56+, phenotypes consistent with non-MHC-restricted cytotoxic T cells. Lack of full engraftment in recipients of T cell-depleted marrow is not always associated with autologous reconstitution and does not always require retransplantation. Y-ISH may be useful for monitoring patients at high risk for graft failure in order to detect adverse trends in mixed chimerism that will alter therapy early after transplantation.
Adolescent↗
Leukostasis: a phenomenon of prolymphocytic leukemia.
We are reporting a case of a patient with prolymphoctic leukemia complicated by fatal leukostasis. Multiple leukemic thrombi and leukoaggregates were demonstrated on postmortem examination in both the brain and lungs. This represents the first report pathologically documenting leukostasis in a chronic lymphoid malignancy.
Brain Diseases↗
Defective T cell colony formation and IL-2 receptor expression in HIV-infected homosexuals: relationship between functional abnormalities and CD4 cell numbers.
HIV infection is known to induce a progressive T helper/inducer (CD4) lymphopenia and to impair the functional activities of residual cells. The present studies examined the relationship between the CD4 cell count and three functional assays: T cell colony formation in semisolid media, the capacity of PHA-stimulated cells to express IL-2 receptors, and their ability to synthesize and secrete IL-2. Cells from antibody-positive homosexuals with normal numbers of CD4 cells (greater than 700/microliters) showed defective reactivity in two assays, colony growth, and IL-2 receptor expression. These defects became progressively more pronounced in homosexuals with moderate (400-700 cells/microliters) and severe (less than 400/microliters) reductions in assays for IL-2 production by PHA-stimulated lymphocytes. Mixing experiments suggest that cells from HIV-infected men nonspecifically inhibit the colony growth of normal cells; this abnormality could be reversed by addition of exogenous IL-2. These data suggest that defective colony growth and reduced IL-2 expression are functional abnormalities directly resulting from HIV infection. Furthermore, these changes can precede the CD4 lymphopenia induced by this viral infection.
Antibodies, Monoclonal↗
Fatal adult respiratory distress syndrome in a patient with Lyme disease.
A dry cough, fever, generalized maculopapular rash, and myositis developed in a 67-year-old woman; she also had markedly abnormal liver function test results. Serologic tests proved that she had an infection of recent onset with Borrelia burgdorferi, the agent that causes Lyme disease. During a two-month course of illness, her condition remained refractory to treatment with antibiotics, salicylates, and steroids. Ultimately, fatal adult respiratory distress syndrome developed; this was believed to be secondary to Lyme disease.
Aged↗
Defective T-cell colony formation and IL-2 receptor expression at all stages of HIV infection.
The T-cell colony assay is a highly sensitive measure of immunological dysfunction. The present study evaluated this in vitro response in asymptomatic HIV-infected homosexuals, those with chronic adenopathy as their only clinical manifestation and patients with either ARC or AIDS. The mean colony count in antibody-positive asymptomatic individuals was significantly reduced when compared to either heterosexual controls or antibody-negative homosexuals. Furthermore, there were no differences in the responses of these antibody-positive individuals and those with chronic lymphadenopathy as their only clinical manifestation. By contrast, patients with AIDS or ARC showed a profound defect; this suggests that the colony assay can detect a functional gradient across the spectrum of HIV infections. Colony growth was correlated with the absolute number of T-helper cells and the ability of PHA-stimulated lymphocytes to express IL-2 receptors; no correlation was found with the number of suppressor/cytotoxic cells or in vitro production of IL-2. Recent HIV seroconverters had normal colony counts but impaired ability to express IL-2 receptors. These data suggest a sequential loss of T-cell function as a result of HIV infection; the earliest manifestations are impaired expression of IL-2 receptors and reduced proliferative responses, as measured in the colony assay.
AIDS-Related Complex↗
High-dose intravenous gamma globulin improves responses to single-donor platelets in patients refractory to platelet transfusion.
Ten patients, with bone marrow failure or malignant disorders, became refractory to platelet transfusions using random, as well as partial or fully HLA-matched, single-donor platelets. To determine its effect on platelet refractoriness, intravenous gamma globulin (IV IgG) was administered at 400 or 800 mg/kg/d for five days, and postinfusion platelet responses were monitored. Platelet transfusion responses following intravenous gamma globulin (IV IgG) were graded as follows: Excellent, 48-hour posttransfusion count greater than 50,000/microL; good, 48-hour count greater than 20,000 but less than 50,000/microL; Fair, increased increment, 48-hour count less than 20,000; and failed, no increased increment. Six of ten patients (60%) had improved responses to selected single-donor platelets (two were excellent, three were good, and one was fair). The time to achieve a platelet transfusion count greater than 25,000/microL ranged from one to nine days of IgG therapy. One individual had sustained benefit (greater than 1 year); the remaining responses persisted for 6 to 8 weeks. These results suggest that IV IgG may be useful in the management of platelet refractoriness, especially in patients receiving single-donor platelets.
Adult↗
1986 update of HIV seroprevalence, seroconversion, AIDS incidence, and immunologic correlates of HIV infection in patients with hemophilia A and B.
A cohort of 181 patients with hemophilia A (149) and hemophilia B (32) cared for at the Hemophilia Center of Western Pennsylvania was followed to determine human immunodeficiency virus (HIV) seroprevalence, seroconversion rate, and clinical and immunologic correlates of HIV infection. By December 1986, 82 (45%) were HIV seropositive, and of these, ten (12%) had developed AIDS, 28 (34%) had symptomatic HIV infection (CDC class III, IV), of whom 14 (17%) had AIDS-related complex (ARC), and 44 (54%) had asymptomatic HIV infection (CDC class II). The HIV seropositive group included 82% of those treated with factor VIII concentrate (97% severe, 5% moderate), 48% of those treated with factor IX concentrate (92% severe, 8% moderate), 10% of those treated with cryoprecipitate (67% severe, 33% moderate), and none of those treated with fresh frozen plasma. Based on 77 serially sampled HIV seropositive hemophiliacs (1977 to 1986), peak seroconversion occurred in 1982, with 14% (11 of 77) occurring since 1984. With increasing time from seroconversion, both T4 lymphocyte number and function (the latter measured by growth in soft agar [T colony assay]) progressively declined; T4 number declined to 135 +/- 26/mm3 (SEM), and colony count declined 1193 +/- 537 (control 3851 +/- 387) by 5 years after seroconversion. In those developing AIDS, total T4 fell below 100/mm3 (33 +/- 8/mm3) at diagnosis. In this cohort, the overall AIDS incidence is 5.5% (12% among the HIV seropositive) and in those seropositive 5 or more years, the AIDS incidence approaches 32%.
Acquired Immunodeficiency Syndrome↗
Antibody responses to immunization of patients with hemophilia with and without evidence of human immunodeficiency virus (human T-lymphotropic virus type III) infection.
Antibody responses after immunization with 23-valent pneumococcal polysaccharide and trivalent influenza virus vaccines were evaluated in 30 adults with hemophilia and in 17 healthy controls. The 30 patients with hemophilia included 13 who were human immunodeficiency virus (HIV) antibody positive with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (group 1), 11 who were asymptomatic HIV antibody positive (group 2), and six who were asymptomatic HIV antibody negative (group 3). Sera were obtained before and 4 weeks after immunization, and levels of antibody were measured by enzyme-linked immunoassay or by hemagglutination inhibition assay. All three groups of patients with hemophilia showed significantly higher preimmunization geometric mean titers of antibodies (groups 1 and 2, fivefold, group 3, 2.8-fold higher), with little increase after pneumococcal vaccine, when compared with controls. Defective humoral responses were noted in groups 1 and 2, with depressed antibody responses after influenza vaccine, significantly elevated levels of IgG and IgM, and depressed blastogenic responsiveness to pokeweed mitogen. Group 3 demonstrated normal responses to pokeweed mitogen, normal antibody responses to influenza vaccine, and normal level of IgG and IgM, although levels of IgG and IgM were higher than those of controls. These data suggest that humoral immune abnormalities are found frequently in patients with hemophilia who are HIV antibody positive. Further, prolonged administration of blood products, regardless of the recipient's HIV status, appears to be associated with polyclonal activation of B cells for T-independent but not T-dependent antigens.
Acquired Immunodeficiency Syndrome↗
Autoreactive erythroid progenitor-T suppressor cells in the pure red cell aplasia associated with thymoma and panhypogammaglobulinemia.
In vitro erythroid culture studies and lymphocyte markers were performed in a patient with a spindle cell thymoma who developed red cell aplasia, panhypogammaglobulinemia, and multiple opportunistic infections. At the time of presentation, erythroid progenitor cells (CFUe, BFUe) were markedly reduced when cultured from marrow mononuclear cells. Removal of T cells from bone marrow mononuclear cells by E-rosetting or complement-mediated lysis with OKT3 pan T cell monoclonal antibody increased growth of erythroid progenitor cells in vitro. Readdition of bone marrow or pleural fluid T cells derived from the thymoma suppressed autologous, but not allogenic, erythroid progenitor cell (CFUe, BFUe) proliferation in vitro. The erythroid progenitor suppressor T cells were predominantly OKT11+, OKT3+, OKT8+ and Ia+ consistent with activated suppressor T cells. Treatment of the patient with cyclophosphamide and corticosteroids reduced marrow lymphocytes fourfold, and a prompt reticulocytosis ensued. After recovery, erythroid progenitor cells were easily detectable. These studies provide new evidence for T cell-mediated suppression of erythropoiesis in a unique subset of patients with red cell aplasia associated with thymoma and hypogammaglobulinemia.
Agammaglobulinemia↗
Telangiectases [corrected] of the anterior chest in homosexual men.
Physical examination by a single clinician showed that 17 of 51 asymptomatic homosexual men and 19 of 26 men with persistent lymphadenopathy had linear telangiectasias in a broad, crescent distribution across the chest. The telangiectasias were commonly associated with erythema in the same distribution. Of the 36 men with telangiectasias, 25 were positive for serum antibody to the human immunodeficiency virus (HIV), whereas only 15 of 41 men without telangiectasias were seropositive (p = 0.001). Biopsy studies of supraclavicular skin from 6 of the men with HIV antibody and telangiectasias showed a characteristic pattern of dilated blood vessels with a perivascular small-cell infiltrate; no endothelial proliferation was noted. This histopathologic pattern was not consistently observed in HIV-seronegative men regardless of whether they had telangiectasias. These data show that telangiectasias of the upper chest are a relatively common finding in homosexual men and that they are significantly, although not exclusively, associated with HIV infection.
Acquired Immunodeficiency Syndrome↗
The effects of interleukins and other soluble factors on T-lymphocyte colony formation.
When plated in semi-solid media, PHA-stimulated human peripheral blood mononuclear cells (PBMC) form discrete T-cell colonies. By contrast, Sephadex G-10 non-adherent (NA) cells (greater than 96% T lymphocytes) show virtually no clonal growth unless cocultured with soluble factors derived from either normal adherent cells or tumour cell lines. Purified IL-1 was able to initiate colony growth of mitogen-stimulated NA cells; cultures containing 20 U of human IL-1 yielded colony counts that were only slightly less than those with PBMC. In addition, recombinant IL-2, free of measurable IL-1, was able to provide the initiating signal required for clonal expansion. Both recombinant and lymphocyte-derived IL-2 were able to enhance the clonal growth of PBMC. Colony growth could be initiated by supernatants derived from short-term cultures of either monocytic (U937, HL60) or B-cell (Raji, Daudi) tumour cell lines. The abilities of these tumour cell lines to promote clonal responses did not correlate with their contents of either IL-1 or IL-2. By contrast, supernatants derived from either K562 (an erythroleukaemic line) or MOLT 4 (a T-cell lymphoma) cells did not provide the initiating signal.
Antibodies, Monoclonal↗
Comparisons of 12-tetradecanoylphorbol-13-acetate (TPA) and PHA as mitogens in the T-lymphocyte colony assay.
12-O-tetradecanoylphorbol-13-acetate (TPA) has multiple effects on the capacity of human T-lymphocytes to form colonies in soft agar. This compound is directly mitogenic for T-lymphocytes; the optimal concentration (100 ng/ml) stimulates an average of 2862 +/- 583 colonies/7.5 X 10(5) cells plated. Furthermore, TPA can act synergistically with PHA to induce a greater number of colonies than can either mitogen alone. Sephadex G10 nonadherent (NA) cells can be directly stimulated by TPA; by contrast, these isolated T cells do not respond to PHA alone. These data indicate that the phorbol ester is able to provide an inductive signal for T cells, allowing them to respond to the plant lectin. Using T-cell subsets isolated by monoclonal antibodies and complement cytotoxicity, PHA is able to induce colony growth of T4 cells; T8 cells fail to respond unless cocultured with exogenous IL-2. TPA can directly stimulate colony formation by both subsets. In cultures stimulated with either TPA or PHA, approximately equal numbers of colonies are generated in the presence of IL-2, suggesting that T4 and T8 cells have similar proliferative capabilities. Phenotypic studies of cells contained in colonies showed differences between the two mitogens. With PHA, more than 98% are both T11 and T3 positive; by contrast, approximately one-third of the cells stimulated by TPA are T11 +, T3-.
Cell Separation↗
Acquired immunodeficiency syndrome in the child of a haemophiliac.
Oral thrush developed during the second month of life in the 5-month-old son of a patient with haemophilia A. He did not feed well, and interstitial pneumonitis, lymphadenopathy, hepatosplenomegaly, and a cellular immune defect consistent with the acquired immunodeficiency syndrome (AIDS) followed. Both parents had signs of pre-AIDS during the year before their son's illness. Transmission presumably occurred in 3 steps: parenterally, via factor VIII concentrate in the haemophiliac; heterosexually, from the haemophiliac to his wife; and vertically, from mother to infant, or via close paternal-infant or maternal-infant contact. This first report of AIDS in the child of a haemophiliac supports the theory that AIDS is caused by an infectious agent. Concentrate-treated haemophiliacs may transmit this agent to their spouses or children, resulting in pre-AIDS or AIDS.
Acquired Immunodeficiency Syndrome↗
Interferon-induced aplasia: evidence for T-cell-mediated suppression of hematopoiesis and recovery after treatment with horse antihuman thymocyte globulin.
A severe and persistent pancytopenia occurred in a 42-year-old woman with a non-Hodgkin's lymphoma following a 10-day course of intramuscular human leukocyte alpha interferon (IFN, 9.0 IU/day). Within 2 weeks of IFN, marrow nucleated myeloid and erythroid precursor cells and megakaryocytes were nearly absent and marrow progenitor cells (CFU-E, BFU-E, CFU-GM) were undetectable. Analysis of marrow lymphocytes revealed that nearly 50% of the cells were E-rosette+, T gamma+, OKT8+ (suppressor/cytotoxic) T-and/or Leu 7+ natural killer (NK) lymphocytes and 50% were IgM Kappa, B1+, B-lymphocytes. In vitro erythroid culture studies were consistent with T-cell-mediated suppression of erythropoiesis. After 2 months without improvement on corticosteroid/androgen therapy, a 10-day course of intravenous antithymocyte globulin (ATG) was administered. This was followed by a prompt reticulocytosis and a rise in blood neutrophils. After ATG therapy, there was a sixfold reduction in marrow suppressor cells, loss of in vitro suppressor effects on erythroid progenitor cells, and complete reversal of blood and marrow OKT4/OKT8 (helper/suppressor) ratios. These studies suggest that interferon may suppress hematopoiesis in some patients by activating marrow suppressor T- and/or NK cells. Treatment aimed at reduction of marrow suppressor cells may aid in hematologic recovery without eliminating the infiltrating lymphoma.
Adult↗