Publications by authors named "Winkelstein A"

Immunohematology encompasses a broad array of clinical disorders in which immune reactions are involved in the pathogenesis of hematologic diseases. Immune reactions can involve the formed elements of the blood, producing hemolytic anemia, thrombocytopenia, or neutropenia. Autoimmune phenomena and drug-induced reactions are the most common mechanisms.

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We evaluated early and late hematopoietic reconstitution in 27 patients with advanced lymphoma, Hodgkin's disease, and breast or ovarian cancer after treatment using high-dose/myeloablative conditioning regimens and autologous peripheral blood stem cell PBSC) transplantation. Eighteen patients (67%) received G-CSF 5 micrograms/kg/day following chemotherapy and nine (33%) were mobilized using G-CSF alone. Each patient had 7 x 10(8) mononuclear cells (MNC) per kg collected.

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Aggressive T-cell neoplasms are an infrequent complication of allogeneic organ and bone marrow transplantation. To date, chronic T-cell lymphoproliferative malignancies have not been described. The present case documents the occurrence of a T-cell large granular lymphocytic leukemia (T-LGL) in a patient following orthotopic liver transplantation.

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While cadaveric vertebral bodies (VB) have long been proposed as a suitable source of bone marrow (BM) for transplantation (BMT), they have rarely been used for this purpose. We have infused VB BM immediately following whole organ (WO) transplantation to augment donor cell chimerism. We quantified the hematopoietic progenitor cell (HPC) content of VB BM as well as BM obtained from the iliac crests (IC) of normal allogenic donors (ALLO) and from patients with malignancy undergoing autologous marrow harvest (AUTO).

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Human umbilical cord blood (CB) is a rich source of hematopoietic stem cells for both research and stem cell transplantation. In clinical studies, it appears that recovery from myeloablative therapy using CB requires significantly fewer cells than a typical allogeneic marrow transplant. This suggests that CB may be enriched for early hematopoietic progenitors.

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Tests that positively identify individuals with ulcerative colitis, distinguishing them from patients with Crohn disease or other causes of colitis, have not been reliable. Genetic predisposition to inflammatory bowel diseases and genetic influence on immune regulation resulted in the clinical evaluation of potential serologic markers. In adults the presence of anti-neutrophil cytoplasmic antibody (ANCA) in serum identifies patients with ulcerative colitis.

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The CD34+ cell fraction of bone marrow and blood contains the hematopoietic stem cells required for marrow reconstitution following myeloablative therapy. Because they are present in small numbers, accurate quantification is often difficult. We have developed a reproducible and sensitive flow cytometric method for CD34+ enumeration of both bone marrow harvests and peripheral blood stem cell collections.

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Glucocorticoids (Gc) are known to modulate protein synthesis by immune cells through binding to a specific receptor (GcR). We outlined the circadian rhythm of plasma cortisol, ACTH, of the peripheral blood mononuclear cells (PBMC isolated by Ficoll-Hypaque technique), and of their subsets CD4, CD8 in 14 asymptomatic HIV+ homosexual men and in nine controls. We also estimated the GcR of the PBMC at 0700 and at 2300 hours, near the peak and nadir of the cortisol rhythm.

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Succinylacetone (SA) proved to be a potent inhibitor of in vitro lymphoproliferative responses. This compound (3.0 mM) reduced the incorporation of 3HTdr by > 90% in mononuclear cell cultures stimulated with PHA, anti-CD3, IL-2 or phorbol dibutyrate-Ca2+ ionomycin.

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Objective: To determine the incidence of a clonal lymphoid disease in patients with chronic rheumatoid arthritis (RA) and neutropenia.

Methods: Lymphocytes from 23 RA patients with either current neutropenia or a history of this complication were studied.

Results: Eight patients had a clonal rearrangement of the T cell receptor beta-chain gene.

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Successful generation of adherent lymphokine-activated killer (A-LAK) cells, highly-enriched in CD3-CD56+ antitumour effector cells, from the peripheral blood of ten patients with acute myelogenous leukaemia (AML) is described. The AML patients were either untreated or in remission. In vitro proliferation of A-LAK cells in patients with AML was generally poor, unless the cells were cocultured with irradiated concanavalin A (ConA)--prestimulated allogeneic PBL or selected lymphoblastoid cell lines (LCL) as feeder cells.

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In an attempt to improve platelet transfusion responses, intravenous immunoglobulin (IV-IgG) was administered to 19 patients who were refractory to random and best available HLA-matched platelets. A response to IV-IgG was defined as two or more successive transfusions of HLA-matched products that provided recoveries greater than 30%. Thirteen of 19 (68%) patients responded to therapy at a median time of 7 days after initiation of IV-IgG (range = 2-17).

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Zidovudine therapy of AIDS patients has been shown to cause only transient improvements in the numbers of circulating CD4+ cells and the in vitro functional activities of cultured lymphocytes. The present studies were undertaken to determine whether prolonged zidovudine therapy enhanced reactivity in two sensitive assays of T-cell function: the ability of phytohemagglutinin (PHA)-stimulated cells to form T-cell colonies and their capacity to express receptors for the growth factor interleukin-2 (IL-2). Treated patients, studied over periods of 20-60 weeks, showed no improvement in colony formation at any time interval, even in plates supplemented with exogenous IL-2.

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A therapeutic trial of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was attempted in a patient with neutropenia and frequent infections secondary to T-gamma lymphoproliferative disease (T-gamma LPD). During the 14 days of subcutaneous rhGM-CSF (500 micrograms/m2/day), the absolute eosinophil count increased from 0 to 9,455/microliters. By contrast, the absolute neutrophil count decreased.

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Uromodulin, an 85 kDa naturally occurring immunosuppressant, was found to selectively and specifically inhibit the ability of IL-1 to induce colony responses by highly enriched suspensions of PHA-stimulated T lymphocytes. Dilutions of 1 x 10(-8) M completely blocked the colony growth of T lymphocytes cultured with 50 U/ml IL-1; 1 x 10(-9) M dilutions reduced scores by 83%. By contrast, uromodulin did not inhibit the responses of unseparated mononuclear cells, isolated T lymphocytes cultured with irradiated adherent cells, or stimulated T cells whose growth was initiated by either IL-2 or a soluble factor derived from Raji cells.

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The effectiveness and toxicities of high-dose cytosine arabinoside with L-asparaginase (HiDAC-ASNase) were evaluated in 41 patients with "poor risk" acute nonlymphocytic leukemia (ANLL). Twenty-four patients had either refractory or relapsed primary ANLL, and 17 had ANLL secondary to prior cytotoxic chemotherapy or an underlying hematologic disorder. The overall complete remission (CR) rate was 37%.

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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.

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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.

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