Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Niemann-Pick disease types A and B are two clinical forms of an inherited lysosomal storage disorder characterized by accumulation of sphingomyelin due to deficient activity of the lysosomal enzyme, acid sphingomyelinase. Patients with both types have hepatosplenomegaly, but only those with type A have nervous system involvement leading to death in early infancy. The residual activities of lysosomal sphingomyelinase in types A and B have never been well characterized because of limitations in both in vitro enzymatic assays and loading tests on intact cells. To evaluate the effective level of sphingomyelinase activity, intact, living cultured Epstein-Barr virus-transformed lymphoid cells were incubated with a radiolabeled sphingomyelin that was first associated to human low-density lipoproteins. This lipoprotein-associated sphingomyelin was targeted to lysosomes, thereby permitting selective hydrolysis by the lysosomal sphingomyelinase. Short-term pulse-chase experiments allowed the determination of the initial rates of degradation; in normal cells, the half-time of sphingomyelin degradation averaged 4.5 h. Whereas cells from the severe neuronopathic type A form of Niemann-Pick disease exhibited about 0.15% residual sphingomyelinase activity, cells from patients with the visceral type B form exhibited about 4%, i.e., 27 times more. Cells from heterozygous Niemann-Pick subjects showed about 70% residual activity. These results provide the first approach to measuring the effective activity of a lysosomal enzyme and represent an accurate method for the differential diagnosis of Niemann-Pick disease types A and B. They also support the hypothesis of relationships among the effective in situ residual enzyme activity, the amount of stored substrate, and the severity of the ensuing lysosomal storage disorder.
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PMID:Accurate differentiation of neuronopathic and nonneuronopathic forms of Niemann-Pick disease by evaluation of the effective residual lysosomal sphingomyelinase activity in intact cells. 805 47

Forty-six nodal T-cell lymphomas, classified according to the updated Kiel classification, were investigated for the presence of Epstein-Barr virus (EBV) DNA by polymerase chain reaction (PCR), EBER 1 and 2 (EBER 1/2) and latent membrane protein-1 (LMP-1) expression. A combination of RNA in situ hybridization and immunohistochemistry was used to establish the phenotype of the Epstein-Barr virus harbouring cells. In 21 of 45 cases Epstein-Barr virus DNA sequences could be detected with the polymerase chain reaction. In 15 cases (14 of 21 EBV PCR positive cases), EBER 1/2 positive cells could be demonstrated. As judged by morphology, EBER 1/2 expression was found in nonneoplastic and neoplastic lymphoid cells. Double staining revealed that more than 80% of the EBER 1/2 harbouring cells, lacked B-, T- or histiocytic markers, suggesting down regulation of T- and B-cell markers by Epstein-Barr virus. In eight of 15 cases some EBER 1/2 positive T-cells (CD3, CD45RO, CD43) morphologically resembling tumour cells were found. In nine of 14 cases tested EBER 1/2 positive non-neoplastic B-cells (CD20) were seen. Based on in situ hybridization results, four patterns of EBER 1/2 positive cells were found, i.e. single cells (< 1 per medium power field (mpf), n = 3), scattered (1-25/mpf, n = 4), clustered (26-100/mpf, n = 5) and diffuse (> 100/mpf, n = 3). In eight of 15 cases a clustered or diffuse pattern of EBER 1/2 positive cells was found and these lymphomas were therefore considered to be strongly associated with Epstein-Barr virus. In these lymphomas LMP-1 expression was found to be associated with an aggressive clinical course and hepatosplenomegaly.
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PMID:Detection of Epstein-Barr virus nucleic acid sequences and protein in nodal T-cell lymphomas: relation between latent membrane protein-1 positivity and clinical course. 831 34

The Epstein-Barr virus (EBV) has been shown to infect T lymphocytes and is associated with two recently recognized human T-lymphoproliferative disorders: childhood EBV-associated hemophagocytic syndrome (VAHS) representing a primary or active EBV infection of T cells in young children, and the EBV-containing T cell lymphoma in adults predominantly affecting the nose, skin and gastrointestinal tract. In both diseases, hemophagocytic syndrome (HS) accounts for the major cause of mortality. The patients developing HS share common clinicopathologic features such as fever, skin lesions, lung infiltrates, hepatosplenomegaly with jaundice, cytopenias, and coagulopathy. The liver, spleen, lymph nodes, and bone marrow usually show florid histiocytic proliferation with hemophagocytosis in addition to the proliferation of atypical T lymphocytes or immunoblasts. The HS in T cell lymphoma may develop simultaneously with initial lymphoma presentation, at tumor relapse, or even during remission. The cytokines, in particular tumor necrosis factor-alpha, released from the EBV-infected T lymphocytes are presumed to cause the histiocytic activation and the subsequent hemophagocytic process. Chemotherapy or antiviral agents fail to arrest the hemophagocytic process in both diseases. Immunomodulatory treatment incorporating etoposide and intravenous immunoglobulin, however, has been effective in the control of the progression of the hemophagocytic process in a substantial number of VAHS patients. Preliminary data suggest that bone marrow transplantation may be a promising way for eliminating both the virus and the proliferating T cells. Further investigations are mandatory for combating this aggressive hemophagocytic process in EBV-associated T lymphoproliferative disorders.
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PMID:Hemophagocytic syndrome in Epstein-Barr virus-associated T-lymphoproliferative disorders: disease spectrum, pathogenesis, and management. 859 Aug 39

Chronic active Epstein-Barr virus infection (CAEBV) is a nonfamilial syndrome that shows a specific immunodeficiency for the Epstein-Barr virus (EBV). Prolonged fever, hepatosplenomegaly, lymphadenopathy, and liver dysfunction were seen in CAEBV, but cardiac complications are rare. An autopsy case of CAEBV with giant coronary aneurysms and aortic aneurysms is reported. The patient was a 5-year-old Japanese girl. At autopsy, the heart weighed 110 g, and bilateral coronary aneurysms were found. Microscopic studies revealed lymphoid vasculitis of coronary arteries, coronary venules, and aortic arteries. Immunohistochemically, infiltrating small lymphocytes were positive for CD3, CD45RO(UCHL-1), CD43(DF-T1). The presence of EBV in most of these T lymphocytes was proven by in situ hybridization using an EBV-encoded RNA-1 (EBER1) probe. To the best of the author's knowledge, pathology of aneurysms caused by lymphoid vasculitis in CAEBV has not been reported until now.
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PMID:Chronic active Epstein-Barr virus infection with giant coronary aneurysms. 865 48

We studied 14 adult patients presenting with fever and cytopenia of the peripheral blood and histiocytic hyperplasia with hemophagocytosis (HHH) in the bone marrow regarding an association of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) by using in situ hybridization (ISH) and also evaluated the clinical and laboratory findings according to the encountered organisms. ISH using a CMV RNA probe demonstrated infected cells in 6 out of 14 cases (43%), and ISH using an EBV EBER RNA probe demonstrated infected nuclei in 5 out of the same 14 cases (36%) of HHH. No cases showed a positive reaction with both probes. Three cases showed a negative reaction with both probes. The mean age of all patients was 29 years; and that of the CMV-positive patients was 27 years and that of the EBV-positive patients was 36 years. Organomegaly was found in 3 out of 6 CMV-positive patients (1 hepatomegaly, 1 splenomegaly, 1 hepatosplenomegaly), and 4 out of 5 EBV-positive patients (lymphadenopathy in all 4 cases, hepatosplenomegaly in 2 cases). One of the CMV-positive case had acute myeloblastic leukemia, and 2 EBV-positive cases had underlying malignancy (1 Hodgkin's disease, 1 non-Hodgkin's lymphoma). Seven out of the 14 HHH cases (50%) died within several months after diagnosis. Nucleic acid hybridization methods can be used for the routine examination of the association of CMV or EBV.
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PMID:In situ hybridization studies of cytomegalovirus and Epstein-Barr virus in reactive histiocytic hyperplasia with hemophagocytosis. 887 10

A 28-year-old man was admitted to our hospital, because of double vision, memory disturbance and dysarthria. These symptoms developed in November, 1994. His mental activity was gradually decreased and he became apathetic. A physical examination on admission was unremarkable. There were no lymphadenopathy, hepatosplenomegaly or skin rash. Neurological examination revealed disorientation, decreased mental activity and left gaze-evoked nystagmus. Neuropsychological tests demonstrated impairment of recent memory and performance but frontal lobe functions were maintained. Laboratory data showed hyponatremia, elevation of antinuclear antibodies and IgG-antibodies to Epstein-Barr virus capsid antigen and Epstein-Barr virus nuclear antigen. A brain MRI revealed multiple lesions in the cerebral subcortex, cerebellum and brainstem. These lesions showed high signal intensity on T2-weighted images and enhanced high signal intensity on T1-weighted images using Gd-DTPA injection. A cystic mass was seen between bilateral lateral ventricles and contacted with the fornix and thalamus. Lymphomatoid granulomatosis was diagnosed by an open brain biopsy, which showed diffuse infiltration of small lymphocytes, histiocytes and plasma cells, especially around the small vessels. Epithelioid granuloma or necrosis was not seen. An immunohistochemical study showed that nearly all lymphocytes were MT-1 positive T lymphocytes. The patient was treated by whole brain irradiation (30Gy) and pulse therapy of methylprednisolone. Multiple lesions in the brain responded to these modalities with complete resolution of the lesions and clinical improvement. In this case, impressive multiple and cystic lesions seen on brain MRI disappeared by whole brain irradiation and steroid. Since etiologies of multiple lesions on MRI includes many possibilities, histological diagnostic methods should be performed to obtain a definitive diagnosis. This is the first case of lymphomatoid granulomatosis that showed multiple and cystic lesions on brain MRI in Japan.
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PMID:[Lymphomatoid granulomatosis of the brain with multiple lesions on MRI]. 893 97

We identified eight cases of T-cell lymphoma with evidence of a gamma delta phenotype over a 13-year period. Seven of these cases conformed to a distinct clinicopathologic entity of hepatosplenic gamma delta T-cell lymphoma. Nearly all of these patients were young adult males (five of seven), with a median age at presentation of 20 years. They presented with marked hepatosplenomegaly, without lymphadenopathy or significant peripheral blood lymphocytosis. Thrombocytopenia was seen in all patients, and five of seven were mildly anemic. The clinical course was aggressive, and despite multiagent chemotherapy, the median survival duration was less than 1 year. The morphologic findings were uniform; a monomorphic population of medium-sized lymphoid cells with moderately clumped chromatin and a rim of pale cytoplasm infiltrated the sinusoids of the spleen, liver, and bone marrow. The cells had a characteristic immunophenotype: CD2+, CD3+, CD4-, CD5-, CD7+, CD16+, CD57-, CD25-, T-cell receptor (TCR)delta +, beta F1-. CD8 was positive in four of seven cases tested, and CD56 was positive in five of six. All cases expressed the cytotoxic granule-associated protein, TIA1, but perforin was detected in only one case. All cases with assessable DNA had a TCR gamma gene rearrangement, and lacked Epstein-Barr virus sequences. Isochromosome 7q was identified in two cases with cytogenetic information. The one case of cutaneous gamma delta T-cell lymphoma differed in its clinical manifestations, histologic appearance, and immunophenotype. We conclude that hepatosplenic gamma delta T-cell lymphoma is a distinct clinicopathologic entity derived from cytotoxic gamma delta T cells, and should be distinguished from other lymphomas of T-cell and natural-killer cell (NK)-like T-cell derivation.
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PMID:Hepatosplenic T-cell lymphoma: a distinct clinicopathologic entity of cytotoxic gamma delta T-cell origin. 912 60

Five paediatric cases of haemophagocytic lymphohistiocytosis (HLH) which showed proliferation of granular atypical lymphocytoid cells in bone marrow are reported. All cases were girls aged 8 months to 4 years who had marked hepatosplenomegaly. Marker analysis on peripheral blood mononuclear cells revealed an increase in the CD3+HLADR+ subset in three cases and the CD3- CD56+ subset in one case. An Epstein-Barr virus genome was detected in three cases, and monoclonality was confirmed in two cases. A characteristic morphology of large granular lymphocytes (LGL) was identified, with elongated bizarre features that resembled horsetail-, tadpole-, cucumber- or shooting star-type configurations on the bone marrow smear. Serum concentrations of soluble interleukin-2 receptor and interferon-gamma were elevated in all cases. All five cases required multi-agent chemotherapy which resulted in two complete remission, two partial remissions and one no response. Refinement of treatment is required for these paediatric GLPD cases which probably comprise a specific high-risk subgroup among secondary HLH patients which had previously escaped notice.
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PMID:Haemophagocytic lymphohistiocytosis in association with granular lymphocyte proliferative disorders in early childhood: characteristic bone marrow morphology. 907 10

Lymphoproliferative disorder of natural killer cells is a heterogeneous disorder, and an association with Epstein-Barr virus (EBV) is suggested in some cases. A Japanese male presenting with recurrent nasopharyngeal problems developed fever, generalized lymphadenopathy, and hepatosplenomegaly. Separated cells from lymph nodes were shown to have a natural killer (NK) cell, CD2(+), CD3(-), CD16(+), CD56(+), HLA-DR(+) phenotype. A progressive abnormality of hepatic function was associated with hepatorenal failure and death. A serologic study suggested reactivated EBV infection. In situ hybridization (ISH) studies showed Epstein-Barr virus-encoded RNA (EBER)-1 in lymph nodes, with lymphocytes infiltrating the liver and tissue from ethmoid sinus surgery 3 years prior to development of obvious lymphoproliferative disease. Polymerase chain reaction performed on lymph node DNA, using oligonucleotide primers specific for the EBV lymphocyte-determined membrane antigen (LYDMA) gene, revealed a single band, suggesting monoclonal proliferation of the tumor. NK activities of the lymphocytes from the lymph node and peripheral blood were markedly decreased. These findings suggest a close relationship between EBV infection and development of NK cell lymphoproliferative disorder.
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PMID:Aggressive natural killer cell lymphoproliferative disorder associated with Epstein-Barr viral RNA. 909 88

Primary lymphoma of the uterine corpus (PLUC) is an extremely rare neoplasm. We report a case of PLUC in a 78-year-old woman with vaginal bleeding without hepatosplenomegaly, adenopathies, or bone marrow infiltration, classified as stage I. A diagnosis of diffuse large B-cell lymphoma was made in endometrial curettage tissue. Immunohistochemical study showed tumoral cells of B-cell nature. Two different polymerase chain reaction (PCR) techniques showed immunoglobulin heavy chain gene rearrangement and we could not demonstrate, with PCR technique, either Epstein-Barr virus or papilloma virus infection. Total hysterectomy with bilateral salpingo-oophorectomy was carried out and adjuvant chemotherapy was given. She was alive and free of disease after a follow-up period of 7 years, and the patient has been in perfect health.
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PMID:Large B-cell lymphoma of the uterine corpus: case report with immunohistochemical and molecular study. 919 Sep 90


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