Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 14-year-old Japanese female with neutropenia showed malignant proliferation of the large granular lymphocytes (LGLs). These LGLs were E rosette+ and Fc(IgG) receptor+ and therefore are referred to as T gamma lymphocytes. They were also Leu-11+ and OKT11+; however, they were clearly negative for Leu-7, OKT3, OKT8, OKM1, and HNK-1 antigens as well as for terminal deoxynucleotidyl transferase activity. Karyotype analysis revealed 47, XXX. The LGLs showed no rearrangement of T cell receptor C beta genes. The natural killer (NK) cell activity against K562 target cells was low, but was significantly augmented after stimulation by recombinant human interleukin 2 (IL 2) in contrast to minimal NK boosting by recombinant human gamma-interferon (gamma-IFN). Such a unique responsive ability to lymphokines was quite similar to that noted in fetal and cord blood cells. These LGLs also demonstrated a considerable increase in antibody-dependent cell-mediated cytotoxicity (ADCC) and lymphokine-activated killer (LAK) activity after a short incubation with IL 2. Although in a resting stage they showed no IL 2 receptor expression as examined by anti-Tac antibody, Tac antigen appeared after IL 2 treatment followed by a marked increase in 3H-thymidine incorporation and a remarkable production of gamma-IFN. To investigate the mechanism of neutropenia, in vitro IL 2-stimulated coculture studies of these cells with normal bone marrow cells were performed. Colony formation of myeloid progenitors (CFU-C) was significantly suppressed. In addition, the conditioned medium from IL 2-stimulated LGLs indicated a remarkable suppression of CFU-C. These results suggest that these LGLs with a Leu-11+, Leu-7- surface phenotype might belong to a unique subset of pre-NK cells that are functionally and phenotypically similar to those represented at any early stage of human ontogeny and that they strongly express Tac antigen under the influence of IL 2 administration, followed by remarkable cell proliferation and gamma-IFN production.
 ...
PMID:Malignant clonal expansion of large granular lymphocytes with a Leu-11+, Leu-7- surface phenotype: in vitro responsiveness of malignant cells to recombinant human interleukin 2. 294 3

We describe a patient with neutropenia associated with increased circulating large granular lymphocytes (LGL). Absolute neutropenia was accompanied by the absence of myeloid precursor cells in the bone marrow. No myeloid progenitor cells (CFU-C) could be detected by in vitro colony culture. The peripheral blood was also remarkable for the presence of a population of large granular lymphocytes demonstrable by conventional staining. These cells in flow microfluorometry studies expressed antigens Leu 4 (T-cell antigen receptor), Leu 7 (natural killer cell marker), Leu 2 (suppressor cell marker), and HLA-DR (activation marker); they lacked Leu 1 (a pan-T cell antigen), Leu 3 (helper cell marker) and Tac (interleukin 2 receptor). Hematopoietic colony formation in vitro improved with addition of corticosteroids to the culture medium or elimination of the LGL population with complement-mediated cytotoxicity. Anti-neutrophil antibodies were present prior to and following therapy. Clinically, administration of prednisone resulted in a normalization of the total white blood cell count and absolute polymorphonuclear cell number, an increase into the normal range of the number of CFU-C, and elimination of the LGL population. In this case of steroid-responsive LGL-associated neutropenia, laboratory studies suggested direct suppression of myelopoiesis by steroid-responsive LGL.
 ...
PMID:Neutropenia associated with large granular lymphocytes responsive to corticosteroids in vitro and in vivo. 358 9

Hemophagocytic lymphohistiocytosis is a life-threatening condition associated with hyperinflammation and multiple organ dysfunction. It has many causes, symptoms, and outcomes. Early recognition is critical for treatment. Fever, cytopenias, coagulopathy, and hepatosplenomegaly are hallmark findings. Identifying the trigger event is crucial but challenging because of the varied presentations and infrequent provider experience. Diagnostic features include anemia, thrombocytopenia, neutropenia, elevated ferritin, hypertriglyceridemia, hypofibrinogenemia, hemophagocytosis (in bone marrow, spleen, or lymph nodes), low or absent natural killer cells, and elevated soluble interleukin 2 receptor assay. Primary treatment goals are eliminating the underlying trigger and suppressing hyperinflammation with steroids, immunoglobulins, or immunomodulators. Specific treatment includes corticosteroids, etoposide, and antithymocyte globulin followed by hematopoietic stem cell transplantation in patients with refractory or relapsing disease. Prompt immunochemical therapy is essential but often complicated by a high risk of treatment-related morbidity and disease recurrence. Despite these challenges, improvements in diagnostic technology and treatment have enhanced survival.
 ...
PMID:Hemophagocytic Lymphohistiocytosis. 3115 46