Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.184 (LasR)
 897 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A virus-associated hemophagocytic syndrome (VAHS) is a non-neoplastic, generalized histiocytic proliferation with prominent hemophagocytosis associated with a systemic viral infection. Epstein-Barr virus (EBV) is one candidate for this association but serologic and molecular biologic studies have been lacking in many cases. Although VAHS is generally a benign process, EBV-associated hemophagocytic syndrome (EBV-AHS) is often fatal and has a relatively high mortality rate. Therefore, EBV-AHS must be distinguished from VAHS caused by other viruses. Recent evidence indicates that the pathophysiology in EBV-AHS appears to be mediated by the unrestricted release of cytokines produced by the EBV-infected T cells. Clinical and laboratory findings, the differential diagnosis, virology studies, pathophysiology, and treatment in EBV-AHS are reviewed.
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PMID:Epstein-Barr virus-associated hemophagocytic syndrome. 778 52

Epstein-Barr virus (EBV) infected cells were examined in three cases of EBV-associated hemophagocytic syndrome (EBV-AHS) by analysis of the heterogeneity of terminal repetitive sequences in the EBV genome, indicating monoclonal expansion of EBV-infected cells in all cases. Involvement of T lymphoid cells was determined by the finding of in situ hybridization using [35S]-labeled RNA probes specific for the small EBV-encoded nuclear RNAs, EBER1 and EBER2, in combination with immunostaining for the TCR-beta chain, CD45RO, CD20, CD30 and CD68 antigens in these three cases. The majority of lymphoid cells showing EBER transcripts were stained by antibodies against CD45RO and TCR-beta. In contrast, EBER-specific signals were not detectable on B cells or hemophagocytic cells. These data support the concept that subclinical EBV-associated T cell proliferation is the primary characteristic of EBV-AHS, rather than proliferations of hemophagocytosing histiocytes.
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PMID:Analysis of the target cell for Epstein-Barr virus infection in Epstein-Barr virus associated hemophagocytic syndrome (EBV-AHS). 839 25

A 32-year-old woman in the 16th week of pregnancy was admitted to our hospital because of high fever. Laboratory findings disclosed pancytopenia and extremely elevated serum LDH and ferritin levels. Coagulation tests showed disseminated intravascular coagulation. Serum soluble interleukin-2 receptor, tumor necrosis factor-alpha, and interleukin-6 levels were high, but serum interferon-gamma was below the detectable limit. Reactive Epstein-Barr virus (EBV) infection was diagnosed on the basis of a high titer of IgG antibodies to the EBV capsid antigen and early antigen. EBV was demonstrated in the peripheral blood and bone marrow cells by polymerase chain reaction. Mature histiocytosis and hemophagocytosis were detected in the bone marrow. A diagnosis of EBV-associated hemophagocytic syndrome (EBV-AHS) was made. Neither prednisolone (PSL 30 mg/day, P.O.) nor methylprednisolone (m-PSL) pulse therapy (1,000 mg/day for 3 days) induced a response. Thereafter, treatment with m-PSL pulse therapy (1,000 mg/day for 3 days) and i.v. administrations of high-dose immunoglobulin (20 g/day for 3 days) in combination with acyclovir (750 mg/day) and gabexate mesilate (2 g/day) induced remission of the disease. Maintenance therapy consisted of PSL (5 mg/day, P.O.) and camostat mesilate (600 mg/day, P.O.). The patient delivered a healthy male infant in the 35th week of pregnancy via natural birth. Reports of pregnant women with EBV-AHS are rare, and the choice of therapy has not yet been established. The present case study suggested the above combination treatment is useful and safe, and capable of changing the fulminant course of EBV-AHS during pregnancy without the use of anticancer drugs.
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PMID:[Epstein-Barr virus-associated hemophagocytic syndrome during mid-term pregnancy successfully treated with combined methylprednisolone and intravenous immunoglobulin]. 1065 79

Primary Epstein-Barr virus (EBV) infection in childhood is usually asymptomatic, but sometimes causes infectious mononucleosis (IM). Very occasionally, IM develops into a life-threatening EBV-associated hemophagocytic syndrome (EBV-AHS). We studied the importance and usefulness of measuring cell-free viral DNA in the serum of patients with these primary EBV infections. Using real-time quantitative polymerase chain reaction, cell-free EBV-DNA was quantified in the serum of nine children with IM and three with EBV-AHS. In the acute phase of IM, an average of 10(2.4) copies/ml of EBV-DNA was detected in 95% of sera. The EBV load gradually decreased and disappeared within 1 month. Patients with EBV-AHS had an extremely high viral load in their sera (10(5.5)-10(7.4) copies/ ml). The viral load persisted longer in these patients, although it decreased in parallel with the improvement of symptoms. These results indicate that cell-free EBV-DNA was frequently detected in patients with primary EBV infection and could, therefore, be used as a marker for EBV infection. Measuring the cell-free EBV-DNA is useful for monitoring the primary EBV infection, especially in EBV-AHS.
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PMID:Monitoring of cell-free viral DNA in primary Epstein-Barr virus infection. 1091 57

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis. However, the animal model for EBV-AHS has not been developed. We reported the first animal model for EBV-AHS using rabbits infected with EBV-related herpesvirus of baboon (HVP). Eleven of 13 (85%) rabbits inoculated intravenously with HVP-producing cells developed fatal lymphoproliferative disorders (LPD) between 22 and 105 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in nine of these 11 rabbits. The peroral spray of cell-free HVP induced the virus infection with increased anti-EBV-viral capsid antigen-IgG titers in three of five rabbits, and two of these three infected rabbits died of LPD with HPS. Autopsy revealed hepatosplenomegaly and swollen lymph nodes. Atypical lymphoid T cells expressing EBV-encoded small RNA-1 infiltrated diffusely in many organs, frequently involving the lymph nodes, spleen, and liver. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by polymerase chain reaction or Southern blot analysis. Reverse transcriptase-polymerase chain reaction revealed both HVP-EBNA1 and HVP-EBNA2 transcripts, suggesting latency type III infection. These data indicate that the high rate of rabbit LPD with HPS induction is caused by HVP. This system is useful for studying the pathogenesis, prevention, and treatment of human EBV-AHS.
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PMID:An animal model for human EBV-associated hemophagocytic syndrome: herpesvirus papio frequently induces fatal lymphoproliferative disorders with hemophagocytic syndrome in rabbits. 1129 May 71

Epstein-Barr virus (EBV) infection has been associated with infectious mononucleosis, EBV-associated hemophagocytic syndrome (EBV-AHS), chronic active EBV infection (CAEBV), lymphomas, inflammatory pseudotumor, lymphomatoid granulomatosis, and nasopharyngeal carcinoma. EBV-AHS and CAEBV are more lethal than infectious mononucleosis with imaging findings of gallbladder wall thickening, pleural effusion, cardiomegaly, and hepatomegaly. EBV infection is also associated with benign and malignant tumors.
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PMID:Spectrum of Epstein-Barr virus infection in Japanese children: a pictorial essay. 1143 30

Virus-associated hemophagocytic syndrome (VAHS) is a non-neoplastic, generalized histiocytic proliferation with prominent hemophagocytosis associated with a systemic viral infection. Although Epstein-Barr virus (EBV) is one candidate virus for this association, thorough serologic and molecular biologic studies to determine the presence of the viral infection have been lacking in many reports. Whereas elevated liver function tests are common findings in patients with VAHS, exudative ascites and abdominal lymphadenopathy are rare. We describe a case of EBV-AHS masquerading as lymphoma in which treatment with intravenous immunoglobulins was associated with complete clinical remission at 2 years and 6 months after the onset. Regardless of the exact mechanism responsible for ascites formation in VAHS, this case adds support to the possible involvement of EBV in patients with abdominal lymphadenopathy and ascites.
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PMID:Epstein-Barr virus-associated hemophagocytic syndrome masquerading as lymphoma: a case report. 1145 62

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS), which is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD), is a distinct disease characterized by high mortality. Treatment of patients with EBV-AHS has proved challenging. To develop some therapeutic interventions for EBV-AHS, we examined the effectiveness of an antiviral agent (vidarabine) or chemotherapy (CHOP), using a rabbit model for EBV-AHS. Fourteen untreated rabbits were inoculated intravenously with cell-free virions of the EBV-like virus Herpesvirus papio (HVP). All of the rabbits died of HVP-associated (LPD) and hemophagocytic syndrome (HPS) between 21 and 31 days after inoculation. Furthermore, three HVP-infected rabbits treated with vidarabine died between days 23 and 28 after inoculation, and their clinicopathological features were no different from those of untreated rabbits, indicating that this drug is not effective at all to treat HVP-induced rabbit LPD and HPS. Three of the infected rabbits that were treated with one course, with an incomplete set of three courses, or with three full courses of CHOP treatment died of HVP-induced LPD and HPS with a bleeding tendency and/or with opportunistic infections. They died on the 26th, 62nd and 105th day after virus inoculation, respectively. CHOP treatment transiently suppressed the HVP-induced LPD and contributed to the prolonged survival time of two infected rabbits. However, it did not remove all of the HVP-infected cells from the infected rabbits, and residual HVP-infected lymphocytes caused recurrences of rabbit LPD and HPS. The most interesting finding of this experiment was observed in the infected rabbit with the longest survival time of 105 days: HVP-negative lymphomas surrounded by HVP-induced LPD developed in the larynx and ileum of this rabbit, causing an obstruction of the lumen. We concluded that these were not secondary lymphomas caused by CHOP treatment, because no suspicious lesions were detected in three uninfected rabbits that were treated with three courses of CHOP for 120 days. It is therefore necessary to clarify the mechanism by which HVP-negative lymphomas associated with HVP-induced LPD can develop. Our data from therapeutic trials using EBV-AHS animal models indicate that vidarabine is not effective as an agent to treat HVP-infected rabbits, and even the cytotoxic chemotherapy of CHOP is not sufficient to cure the HVP-infected rabbits or to prolong the survival time of infected rabbits. Further studies will therefore be required to develop better therapies to treat EBV-AHS.
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PMID:Therapeutic trials for a rabbit model of EBV-associated Hemophagocytic Syndrome (HPS): effects of vidarabine or CHOP, and development of Herpesvirus papio (HVP)-negative lymphomas surrounded by HVP-infected lymphoproliferative disease. 1297 84

We report herein a 21-year-old hepatitis B virus (HBV) female carrier who developed persistent fever, lymphadenopathy and pancytopenia in September of 2000. Hemophagocytes were found in the bone marrow smears. Epstein-Barr virus (EBV) serology showed positive for VCA-IgG, IgM and EB-ER and negative for EBNA. The EBV genome was detected in the peripheral blood. The patient was diagnosed as having EBV-associated hemophagocytic syndrome (EBV-AHS) and received chemotherapy. Although she was treated with lamivudine three months after the initiation of chemotherapy, she developed severe hepatitis. She recovered from the hepatitis through a combination of plasma exchange, immunosuppressive and antiviral therapies. Because of the refractoriness of her EBV-AHS to chemotherapy, she received allogeneic peripheral blood stem cell transplantation (PBSCT) from her HLA-identical brother. Hepatitis B did not recur after the PBSCT under administration of lamivudine. The EBV genome in the peripheral blood disappeared soon after the PBSCT but it was revealed again after the initiation of prednisolone for the treatment of acute GVHD. A donor lymphocyte infusion (DLI) was given on day 169 and the EBV genome copy number in the peripheral blood gradually decreased and disappeared. Although the origin of the EBV-infected cells could not be determined as being from the host or donor, DLI was a useful treatment for the recurrence of EBV infection after allogeneic stem cell transplantation for EBV-AHS.
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PMID:[Allogeneic peripheral blood stem cell transplantation for a hepatitis B virus carrier with Epstein-Barr virus associated with hemophagocytic syndrome]. 1519 50

The primary infection of Epstein-Barr virus (EBV) may results in hemophagocytic syndrome, known as EBV-associated hemophagocytic syndrome (EBV-AHS), but the clinical risk factors complicating this fatal disease in children with infectious mononucleosis (IM) are unknown. The aim of this study was to identify clinical features of EBV-AHS and to evaluate the curative effect of HLH-2004 protocol. The clinical and laboratory data of 644 IM children including 27 children developed into EBV-AHS and 43 HPS children associated with other diseases were retrospectively analyzed and logistic regression was used to identify the clinical risk factors complicating EBV-AHS. The results showed as follows: (1) the prevalence of EBV-AHS in IM children was 4.2% (27/644), and the prevalence in group aged younger than 3 years was higher than in other age groups. The incidence age of EBV-AHS was significantly younger than that of other HPS patients; (2) Liver function damage of group aged older than 7 years was much more severe in HPS patients. (3) Compared with other HPS patients, male patients were more common and liver function damage was severe in EBV-AHS patients, especially in the patients aged at 2 years or younger. (4) The fatality rate in the EBV-AHS patients was 37.0% (10/27). (5)After treatment with HLH-2004 protocol, the fatality rate in patients with EBV-AHS decreased from 50.0% to 18.2%, the overall survival (OS) of 3 years significantly increased (P = 0.032). It is concluded that IM is a benign self-limited disease, of which only about 4.2% patients will develop into EBV-AHS. Clinical risk factors identified in this study may be helpful for early diagnosis of IM children with complicated EBV-ASH, the HLH-2004 protocol can obviously improve prognosis of EBV-HPS.
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PMID:[Clinical analysis of Epstein-Barr virus-associated hemophagocytic syndrome in children]. 2362 54


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