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

Although lymphocytosis and neutropenia are commonly associated with infectious mononucleosis (IM), the precise mechanisms involved remain unclear. Accumulated evidence has revealed that the apoptosis-mediating system, Fas receptor/Fas ligand (Fas-R/Fas-L), plays an important role in this disease. Recently, lymphocytes, monocytes, and neutrophils have been reported to constitutively express Fas-R, and the Epstein-Barr virus (EBV) has been shown to activate, in addition to B cells, peripheral blood CD8+ T cells, monocytes, and neutrophils. We elucidated cell surface expression and serum concentrations of Fas-R and Fas-L in patients with IM in an effort to more clearly define the role and contribution of apoptosis in this disease. The expression of lymphocyte surface Fas-L and Fas-R was significantly increased in patients with IM (P < .005 and P < .001, respectively), and among lymphocytes, CD4+ or CD8+ populations contained Fas-R+ as well as Fas-R- subpopulations. The constitutive Fas-R expression levels of monocytes and neutrophils were also increased in IM. Moreover, serum levels of both soluble Fas-L and Fas-R were significantly higher in patients with IM than in healthy volunteers (P < .001 and P < .0001, respectively). Positive relationships between the number of peripheral blood CD95+ lymphocytes and white blood cell count, number of lymphocytes, or number of CD4+ or CD8+ lymphocytes were observed. Our results suggest that the Fas-R/Fas-L system might play a role in eliminating EBV-infected or -activated peripheral blood cells by cell-to-cell contact or in an autocrine and/or paracrine fashion in patients with IM.
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PMID:Cellular expressions and serum concentrations of Fas ligand and Fas receptor in patients with infectious mononucleosis. 1118 89

We describe a case of T-cell large granular lymphocyte (LGL) leukaemia that transformed into a large-cell T-cell lymphoma 11 years from diagnosis. A 29-year-old asymptomatic female presented in 1989 with lymphocytosis, neutropenia and mild bone marrow infiltration. The circulating cells were LGL with a CD2+, CD3+, CD8+, CD4-, CD16+, CD56+, CD57- phenotype. In August 2000, she developed fever, a large submandibular mass and hepatosplenomegaly. Biochemistry showed abnormal liver function tests and raised lactate dehydrogenase (LDH) levels. A serological screen for Epstein-Barr virus, cytomegalovirus, human T-lymphotropic virus-I, human herpes virus (HHV)-6 and HHV-7 was negative. Histology of the mass was consistent with the diagnosis of peripheral T-cell lymphoma composed of large cells, and immunohistochemistry showed that the lymphoma cells had a phenotype identical to the mature LGL. Molecular analysis with the polymerase chain reaction (PCR) demonstrated rearrangement of the T-cell receptor (TCR) gamma-chain gene with a band of identical size in both bone marrow mature LGL and lymph node cells. The patient was treated with CHOP (cyclophosphamide, vincristine, doxorubicin and prednisolone), resulting in the disappearance of the mass and improvement of the hepatosplenomegaly, LDH and liver abnormalities. She underwent splenectomy, and spleen histology showed involvement by T-cell LGL leukaemia with no evidence of transformation. This case illustrates that transformation or Richter syndrome may occur in a minority of patients with T-cell LGL leukaemia, a disease that has a benign clinical course in most cases. This is the first case documented by molecular methods of the transformation of the pre-existing clone.
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PMID:Transformation of T-cell large granular lymphocyte leukaemia into a high-grade large T-cell lymphoma. 1184 12

Cellular immunity to viral and fungal antigens is often suppressed after stem cell transplantation. Viral infections, in particular infections with cytomegalovirus and Epstein-Barr virus, are often reactivated after allogeneic stem cell transplantation. Pathogenetic factors are immune deficiency and T-cell stimulation in the course of graft-versus-host reactions. Fungal infections are opportunistic infections derived with ubiquitous microorganisms. Immune deficiency, neutropenia, steroid treatment, and antibiotic treatment contribute to the pathogenesis. The study of viral and fungal immunity after allogeneic stem cell transplantation gives insight into the reconstitution of the immune system and tolerance.
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PMID:Cellular immunity to viral and fungal antigens after stem cell transplantation. 1239 69

This retrospective study included 18 pediatric cases (median age, 3 years) with pathologically proved hemophagocytic syndrome (HPS) from a single institution during 1992 and 2001. There were 9 males and 9 females. Prolonged fever, cytopenia, liver dysfunction and hepatomegaly were the most common features at presentation. Sixteen (88.9%) cases were previously healthy. The case fatality rate was 61.1%, and all fatal cases died within 2 months of disease onset. The infectious agents associated with HPS were identified in 11 cases (61.1%), and 8 (72.7%) of them had evidence of Epstein-Barr virus (EBV) infection or reactivation. Underlying immunologic disorder or neoplastic disease was identified in 11.1% of the cases. Children less than 3 years of age with HPS were more vulnerable to neutropenia-associated bloodstream infection (85.7% vs 27.3%; p=0.025). Pseudomonas aeruginosa (3) and Candida tropicalis (2) were the 2 most commonly isolated pathogens. Regarding specific management of HPS, intravenous immunoglobulin and steroids were the first-line agents and were administered in 16 cases and 11 cases, respectively, while etoposide was administered in 5 refractory cases during the late phase of disease. Most HPS occurred in previously healthy children, and a substantial proportion of cases rapidly progressed to death. Most cases were associated with viral infection, particularly EBV, and young children tended to develop neutropenia-associated bacteremia during the active phase of the disease.
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PMID:Hemophagocytic syndrome: a review of 18 pediatric cases. 1522 Oct 35

Although novel therapies for chronic lymphocytic leukemia have resulted in higher hematologic response rates, the complete eradication of disease rarely occurs. Alemtuzumab (Campath-1H) seems to be extremely effective in this role in pretreated patients. The authors used a molecular semiquantitative polymerase chain reaction (PCR) method to assess the ability of alemtuzumab to induce PCR negativity in eight patients pretreated with fludarabine. IgH rearrangement was coamplified with a housekeeping gene and fluorescent PCR products were analyzed on a DNA automatic sequencer. Each patient was evaluated at diagnosis, after fludarabine, and after Campath-1H. The median interval between the last therapy course with fludarabine and the start of Campath-1H was 14 weeks. Patients received subcutaneous doses up to 10 mg, three times a week, for 12 weeks, with a median dose of 190 mg. After six cycles with fludarabine, only one patient (12.5%) achieved molecular remission, and in three other patients IgH levels decreased by 0.5 to 1 log. At the beginning of Campath-1H administration, all patients were PCR positive, including the one previously found to be negative. At the end of treatment, five patients achieved molecular remission (62.5%), four of them within 1 month after the end of therapy. Seventy-two percent of responses, with 43% of complete responses, were documented on bone marrow smears. A significant reduction of lymph node and spleen diameters was noted in 50% and 33% of patients, respectively. Four patients showed grade 2 skin reaction at the site of the subcutaneous injection and grade 1 or 2 fever. Two patients developed neutropenia (grade 2 and 3) and two hemolytic episodes. Three patients showed cytomegalovirus and one herpes zoster and Epstein-Barr virus reactivation. These results show that Campath-1H represents an efficacious in vivo purging tool with a safe profile.
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PMID:Quantitative molecular evaluation of minimal residual disease in patients with chronic lymphocytic leukemia: efficacy of in vivo purging by alemtuzumab (Campath-1H). 1531 47

The common observation of Epstein-Barr virus (EBV) viremia in pediatric recipients of renal transplants and the occurrence of an EBV-related pulmonary leiomyoma prompted us to intensify the follow-up of EBV infections from 1995 to October 2000. Follow-up included serology and detection of viral DNA in blood using a semi-quantitative nested polymerase chain reaction (PCR) and later a real-time PCR with higher sensitivity. The aim of this study was the early detection of primary infections or reactivations. We obtained 250 samples from 32 patients. EBV DNA detection was consistently negative in 14 patients. There were 5 patients that were considered at risk for post-transplant lymphoproliferative disease, as they were EBV seronegative and were given a kidney from a positive donor. Of these, 4 had at least one episode of high-level EBV viremia. During these episodes, an absence of noticeable symptoms that could be related to EBV was noted for all but 1 patient. This child presented with severe neutropenia 1 month after grafting and, 28 months later, several nodules of pulmonary leiomyoma, which were found to be EBV related. Four episodes of high-level viremia were observed before the discovery of the leiomyoma. Viral DNA detection is important for the follow-up of such patients that are especially at risk of serious complications of EBV infections.
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PMID:Long-term follow-up of Epstein-Barr virus viremia in pediatric recipients of renal transplants. 1560 68

Allogeneic stem cell transplantation (SCT) using a myeloablative (MA) conditioning regimen is limited to relatively young patients because of increased transplant-related mortality in elderly patients. Nonmyeloablative (NMA) conditioning regimens have been developed aiming to reduce transplant mortality. In this study, we set out to evaluate the post-transplant occurrence of infectious complications in recipients of grafts from human leukocyte antigen (HLA)-identical sibling donors treated with either NMA or MA conditioning regimens. Data of 78 consecutively treated patients were analyzed. An NMA conditioning regimen was used in 40 patients and an MA regimen in 38 patients. A significantly lower rate of episodes of febrile neutropenia (0% vs. 34%, P<0.01) and post-transplant Epstein-Barr virus reactivations (0% vs. 18%, P<0.05) was found in SCT recipients treated with an NMA conditioning regimen compared with an MA conditioning regimen. Furthermore, fewer invasive fungal infections (2% vs. 12%, not significant) were diagnosed in the NMA group. The incidence of cytomegalovirus (CMV) reactivations and bacterial infections was low in both groups (CMV reactivations: 13% in both groups; bacterial infections: 10% in the NMA group vs. 8% in the MA group), while CMV disease developed in only 1 patient. Overall, compared to our MA regimen, we found a very low rate of infectious complications after NMA SCT.
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PMID:Low incidence of infectious complications after nonmyeloablative compared with myeloablative allogeneic stem cell transplantation. 1576 35

Infection with the human immunodeficiency virus (HIV) is associated with an increased risk of systemic non-Hodgkin's lymphoma, Hodgkin's disease, and primary central nervous system lymphoma (PCNSL). Systemic lymphoma usually involves extranodal sites (80%-90%) and is usually of intermediate-grade (diffuse large-cell or immunoblastic( or high-grade (diffuse small noncleaved) histology. Approximately one third to one half of patients are cured with the cytotoxic treatment regimens that are used in immunocompetent patients with lymphoma. Careful attention must be paid to appropriate treatment of HIV infection and to primary and secondary infection prophylaxis. Colony-stimulating factors are commonly used in conjunction with cytotoxic therapy because of the high risk of febrile neutropenia. Patients with HIV-associated Hodgkin's disease also frequently have extranodal involvement and mixed cellularity histology, features associated with an adverse prognosis in immunocompetent patients. Treatment regimens used to treat Hodgkin's disease in immunocompetent patients have been used with some success, although the prognosis is not favorable in HIV-infected patients with PCNSL is generally poor because such patients typically present with advanced immunodeficiency (CD4 <50/microL), and the lymphoma often relapses after transient initial response to whole brain irradiation. There are anecdotal reports of responses to therapy directed against Epstein-Barr virus (ie, high-dose zidovudine, gancyclovir, and interleukin-2).
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PMID:Human immunodeficiency virus-associated lymphoma. 1622 26

Epstein-Barr virus (EBV) is an oncogenic human herpesvirus that persistently infects approximately 90% of the world's population. Such a remarkably sustained of viral infectivity relies on EBV's ability to evade the host immune defenses. A crucial part of this anti-EBV response is mediated by cytotoxic CD8+ T lymphocytes, which maintain a life-long control over proliferating latently-infected B cells in order to prevent these from giving rise to lymphomatous diseases. On the other hand, little has been done to assess the role of phagocytes-mediated innate immunity in the pathogenesis of EBV infection. In the course of primary EBV infection, episodes of neutropenia and monocytopenia can be observed during the acute phase of infection. According to the role of those cells in the non specific and specific immunity, such a decrease in circulating phagocytes may then temporarily affect the immune defense and potentially influence the outcome of EBV infection. Recent studies have demonstrated that EBV infects both neutrophils and monocytes and modulates several of their biological functions. This review covers the current state of our knowledge relative to the role of neutrophils and monocytes in EBV pathogenesis and describes the nature of countermeasures deployed by EBV against these cells.
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PMID:Epstein-Barr virus immunossuppression of innate immunity mediated by phagocytes. 1654 76

Griscelli syndrome (GS) was diagnosed in a 2-year-old patient with oculocutaneous albinism and immunodeficiency, but sequencing of RAB27a revealed only a heterozygous mutation. Due to impaired natural killer (NK) and T-cell cytotoxicity implying a high risk of developing hemophagocytic lymphohistiocytosis (HLH), he was prepared for hematopoietic stem cell transplantation (HSCT). Unexpectedly, a severe bleeding episode occurred that led to the demonstration of disturbed platelet aggregation, reduced plateletdense granules, and impaired platelet degranulation. In combination with neutropenia, this suggested the diagnosis of Hermansky-Pudlak syndrome type II (HPSII) and a novel homozygous mutation in AP3B1 was detected. None of the 3 reported HPSII patients had developed HLH, and our patient seroconverted to Epstein-Barr virus (EBV) without clinical symptoms. HSCT was therefore withheld, and granulocyte-colony-stimulating factor (G-CSF) therapy was initiated and prevented further bacterial infections. At 3 years of age, however, the patient developed, without an obvious trigger, fulminant HLH that was resistant to therapy. This patient shows that careful clinical and molecular diagnosis is essential to differentiate the complex disorders of lysosomal trafficking. HPSII belongs to the group of familial hemophagocytic syndromes and may represent an indication for HSCT.
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PMID:Lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type II. 1655 69


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