Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 64-year-old woman with a syndrome of thymoma, severe hypogammaglobulinemia, seemingly normal cell-mediated immunity and aplastic anemia, was found to have virtually no immunoglobulin- (Ig) bearing peripheral blood lymphocytes (PBL). However, 7.8 +/- 3.4% of the PBL were positive for another B-cell marker, the receptor for aggregated IgG, while the remaining cells bound sheep erythrocytes. Those cells which were aggregate-reactive appeared to be immature or incomplete B cells. Cultures of peripheral blood leukocytes from the patient in various serum-containing media were studied by 3 independent technics for the development of lymphocyte surface Ig and for Ig in the culture supernatants. In vitro the patient's cells were able to develop surface Ig in media supplemented with fetal calf serum (FCS) or normal serum; in media supplemented with autologous serum, the cells developed no surface Ig. During the cultures in FCS, human Ig determinants became detectable in the medium, and both medium and cell-surface Ig underwent a shift from mu determinants early in the culture period to gamma and alpha determinants later. The development of Ig on the cells was not inhibited by the presence of autologous serum if FCS was included in the medium. These data support the concept that a factor, missing from this patient's serum, is required at an early stage in the maturation of the B cell. A patient with X-linked agammaglobulinemia had a population of circulating lymphocytes with surface characteristics similar to the B cells of the thymoma case. In contrast, no Ig synthesis by this patient's cultured cells could be demonstrated, indicating a different level of block in the 2 cases despite their similarity at the level of the cell surface.
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PMID:B lymphocytes lacking surface IG in patients with immune deficiency: initiation of IG synthesis in culture in cells of a patient with thymoma. 5 98

Investigation of a family with cancer in boys revealed that at least 20 males had the X-linked recessive lymphoproliferative syndrome. A variety of phenotypes occurred: aproliferative phenotypes consisted of aplastic anemia, agranulocytosis or acquired hypogammaglobulinemia; and proliferative phenotypes of B cells included disorders associated with the Epstein-Barr virus, American Burkitt's lymphoma, immunoblastic sarcoma of B cells, fatal infectious mononucleosis or plasmacytoma. The lymphoproliferative disorders observed in males could have resulted from an immunodeficiency to Epstein-Barr virus. The variable phenotypic expression could have resulted from individual differences in the viral dose, duration of exposure and age at which the boys were exposed to the virus. Aproliferative phenotypes such as acquired hypogammaglobulinemia could have ensued from excessive suppressor-cell activity on B cells, whereas proliferative phenotypes such as Burkitt's lymphoma or fatal infectious mononucleosis could have resulted from infection by Epstein-Barr virus and failure to stop proliferation of B cells.
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PMID:Variable phenotypic expression of an X-linked recessive lymphoproliferative syndrome. 19 60

Peripheral blood lymphocytes from 14 patients with idiopathic aplastic anemia were examined to determine their capacity to differentiate into immunoglobulin (lg) producing cells in the presence of pokeweed mitogen (PWM). Four patients had hypogammaglobulinemia. Lymphocytes from ten patients without and one with hypogammaglobulinemia were capable of differentiating into lg-producing cells. Lymphocytes from three patients with hypogammaglobulinemia, however, were unable to differentiate. Coculture experiments showed that in one patient helper activity of T cells was impaired, in another patient B cells could not be stimulated by PWM to differentiate even in the presence of normal T cells, and in a third patient both the helper function of T cells and the capacity of B cells to differentiate into lg-producing cells were affected. These results suggest that differentiation of lymphoid cells is impaired in some cases of idiopathic aplastic anemia associated with hypogammaglobulinemia.
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PMID:Pokeweed mitogen-induced B cell differentiation in idiopathic aplastic anemia associated with hypogammaglobulinemia. 30 48

The X-linked lymphoproliferative syndrome (XLP), also known as Duncan's disease, is an X-linked recessive disorder that is characterized by the inability of affected individuals to mount a sufficient immune response to Epstein-Barr virus (EBV). After EBV primary infection, male family members suffer from severe infectious mononucleosis (IM), aplastic anemia, hypogammaglobulinemia, and a spectrum of lymphoproliferative diseases. Autosomal mode of inheritance with similar symptoms as in XLP has been reported. We have studied two families with EBV-associated syndromes and an X-linked and an autosomal mode of inheritance, respectively. Affected family members presented with severe IM, hemophagocytosis, aplastic anemia, acquired hypogammaglobulinemia, and B-cell lymphoproliferative diseases.
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PMID:Epstein-Barr virus-associated lymphoproliferative syndromes: studies in two European families. 164 73

Patients with X-linked lymphoproliferative (XLP) disease are characterized by extreme vulnerability to Epstein-Barr virus (EBV). Following infection with EBV, affected males develop fatal infectious mononucleosis (IM), hypogammaglobulinemia (H), or non-Hodgkin's lymphoma (NHL). In addition, hyper IgM, red cell aplasia, necrotizing lymphoid vasculitis (NLV), and aplastic anemia occur rarely. The recent use of DNA restriction fragment length polymorphism (RFLP) probes in linkage with the XLP gene now permit detection of affected males prior to primary EBV infection. We have measured immunoglobulin class and subclass levels in sera from EBV-negative males who were either positive or negative for the XLP genotype by RFLP analysis. Elevated IgA or IgM and/or variable deficiency of IgG, IgG1, and IgG3 occurred in the sera of 13/13 RFLP-positive, EBV-negative males. No consistent abnormalities were noted in 14 RFLP-negative, EBV-negative males. We conclude that the immune defect in XLP is not solely EBV-specific, although EBV is responsible for most of the morbidity and all of the mortality. Further, serial measurement of Ig levels may provide information regarding status of EBV-negative males at risk where RFLP analysis is uninformative or in families where sporadic cases of fatal IM, acquired hypogammaglobulinemia or NHL have occurred, but wherein the genotype of XLP cannot be documented.
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PMID:Immunoglobulin class and subclass deficiencies prior to Epstein-Barr virus infection in males with X-linked lymphoproliferative disease. 168 54

The clinical effect of recombinant human granulocyte colony-stimulating factor (rG-CSF), produced by Chinese hamster ovary cells, was studied in 27 patients with childhood neutropenias. The sample consisted of 8 patients with congenital neutropenia (Kostmann type), 9 with neutropenia with miscellaneous causes (5 chronic benign, 2 associated with hypogammaglobulinemia, 1 drug-induced, and 1 hypoplastic type), 3 with cyclic neutropenia, and 7 with severe aplastic anemia. The rG-CSF was given subcutaneously (or in a few cases intravenously) at a dose of 2 micrograms/kg/day for 7 days and 5 micrograms/kg/day for additional 7 to 28 days in cases with poor response. The rG-CSF was effective in 18 of 27 cases (67%). Patients with congenital neutropenia and aplastic anemia responded less frequently and poorly. The mean level of absolute neutrophil counts of 8 congenital neutropenia cases increased from 88/microliters to 2,718/microliters. That of 9 miscellaneous cases changed from 189/microliters to 7,224/microliters at a dose of 2 micrograms/kg/day. In 7 aplastic anemia cases pretreatment level of 220/microliters rose to 851/microliters, usually after increasing the dose up to 5 micrograms/kg/day. The rG-CSF was apparently effective in 3 cases of cyclic neutropenia. In any type of neutropenia, the effect was largely transient; after the discontinuation of rG-CSF, the absolute neutrophil counts tended to decrease to pretreatment levels within 1 to 2 weeks. The G-CSF was well tolerated, and only one case with mild lumbago and another with minimal elevation of transaminases were observed. We conclude that the rG-CSF can be effective for treating various types of childhood neutropenia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of recombinant human granulocyte colony-stimulating factor (rG-CSF) on childhood neutropenias]. 171 Feb 94

We have used limiting-dilution clonal analysis (LDA) in microwells to study the inhibitory effects of T lymphocytes (T-cells) or natural killer (NK) cells on human marrow progenitor cell growth. In four subjects with normal hematopoiesis, the growth of progenitors showed single-hit kinetics both before and after T-cell removal, indicating that, in the presence of colony-stimulating activity, T-cell have no effect on progenitor growth. In a patient with marrow hypoplasia associated with thymoma, hypogammaglobulinemia, and an increased number of suppressor T-cells (Good's syndrome), the progenitor growth deviated from linearity, demonstrating the presence of cells with suppressor activity. After T-cells were removed from this sample, the progenitor growth showed single-hit kinetics. The suppressive action of E-rosette-positive cells with NK or cytotoxic activities was also suggested in a patient with severe combined immune deficiency and in a patient with T gamma lymphocytosis. Poor progenitor-cell growth in three other patients with aplastic anemia was not significantly altered by T-cell removal. Thus, LDA of human hematopoietic progenitors is useful for evaluating cell-mediated interactions affecting hematopoiesis. This method may facilitate elucidation of mechanisms of myelosuppression in clinical settings.
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PMID:Cell-mediated suppression of human hematopoiesis: evaluation by limiting-dilution analysis of hematopoietic progenitors. 281 15

Epstein-Barr virus (EBV) infects virtually everyone by adulthood, and a lifelong latency is maintained. It infects children silently, whereas the majority of adolescents have infectious mononucleosis (IM). Children who have IM before 5 years of age are often heterophil negative; EBV-specific antibodies are required for diagnosis. On rare occasions the symptoms of IM may persist in a chronic or recurrent form, and fatal infectious mononucleosis occurs rarely. Depending on the type and degree of immune deficiency and the time the EBV infection occurs in the life cycle, various atypical outcomes can occur. Children with primary immune deficiency can have fatal or chronic IM, malignant B cell lymphoma, virus-associated hemophagocytic syndrome, aplastic anemia, or acquired hypogammaglobulinemia. The various outcomes of the EBV infections are likely governed by the immune response of the individual. The increased frequency of B cell neoplasms in immunodeficient patients is likely due, in part, to EBV. Individuals with acquired immune deficiency disorders such as AIDS or allograft recipients may develop malignant B cell lymphomas which tend to be polyclonal, but which may progress through stages of oligoclonality to monoclonality. This conversion likely results from specific reciprocal chromosomal translocations such as t(8;14), which is seen in Burkitt's lymphoma. Detection of EBV in immunodeficient patients is achieved by EBV-specific antibody studies or isolation of virus by obtaining spontaneous lymphoblastoid cell lines from peripheral blood, isolating virus from throat washings, or identifying EBV genome by molecular hybridization techniques. Prevention of primary immune deficiency by early detection and genetic counseling and monitoring of patients for occurrence of EBV infection may lead to early treatment. Acyclovir and immunoglobulin therapy can be of value in some patients with active EBV infection.
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PMID:Epstein-Barr virus: the spectrum of its manifestations in human beings. 303 69

The graft-versus-host reaction (GVHR) in both mice and humans can lead to the development of a broad spectrum of clinical and pathological symptoms. These symptoms are strikingly similar to those of a number of diseases of proven or presumed immunological origin, such as systemic lupus erythematosus (SLE), other collagen vascular diseases, lymphoproliferative disease, and aplastic anemia. The purpose of our investigation was to describe the immunological and pathological events that take place in the course of graft-versus-host disease (GVHD) and to gain insight into the cellular mechanisms underlying these events. To this end, a model was employed in which nonirradiated F1 mice were used as recipients of parental lymphoid cells. By pathological manifestations, 2 basic forms of GVHD can be distinguished in such non-irradiated F1 recipients: One is acute GVHD which is often lethal. It is characterized by a variety of suppressive (hypoplastic) pathological symptoms, including a severe hypoplasia of the lymphohemopoietic system accompanied by aplastic anemia and hypogammaglobulinemia. The other basic form is characterized by stimulatory symptoms, such as persistent lymphoid hyperplasia, formation of autoantibodies, and development of pathological symptoms reminiscent of SLE and other collagen vascular diseases. The suppressive pathological graft-versus-host (GVH) symptoms are caused by T suppressor/killer (TS/K) cells of the donor which react towards allogeneic class-I-structures of the F1 recipient's major histocompatibility complex (MHC). The stimulatory pathological GVH symptoms, by contrast, are caused by donor T helper (TH) cells which react toward the recipient's allogeneic class-II-MHC structures. The possible implications of these observations for the pathogenesis of a number of GVH-like diseases in humans are discussed. The hypothesis is advanced that some of these GVH-like conditions, which arise either e causa ignota or after exposure to certain viruses or drugs, are caused by T lymphocytes reacting against self-MHC structures on lymphohemopoietic cells that were rendered "foreign". By analogy to GVHD, it is conceivable that the development of either stimulatory or suppressive GVH-like symptoms in individuals exposed to a given virus or sensitizing drug depends not on the etiologic agent per se, but on whether the predominant response is made by the individual's TH or TS@K cells. This, in turn, might depend on whether the agent becomes immunogenic in combination with class-II or class-I alloantigens.
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PMID:Pathogenesis of graft-versus-host reactions (GVHR) and GVH-like diseases. 315 4

We have investigated T cell abnormalities present in blood of two patients with aplastic anaemia and hypogammaglobulinaemia. There was a marked increase in class II, major histocompatibility complex, HLA-DR+ antigen, and interleukin-2 receptor (Tac+) bearing CD4+ helper/inducer T cells, and a concurrent reduction of CD8+ suppressor/cytotoxic T cells. These CD4+ T cells produced an elevated proliferative response to phytohaemagglutinin and concanavalin A. Interestingly, the T cell subset mainly responsible for elevated production of the lymphokine, interleukin-2, under the stimulus of phytohaemagglutinin, was characterized as belonging to a CD4+ T cell subset. Functional studies, using a pokeweed mitogen driven IgG, IgA and IgM synthesis, demonstrated a correlation between CD4+ T cell deficient helper function for B cell differentiation and the clinical finding of the patient's hypogammaglobulinaemia.
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PMID:Phenotypic and functional T cell subset abnormalities in patients with aplastic anaemia and hypogammaglobulinaemia. 326 16


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