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)

Vectors encoding immunostimulatory genes are under investigation for their use as adjuvants for immunotherapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a prominent candidate gene for this approach because this cytokine can prime immune responses to 'self' tumour or other weak antigens. Prior studies suggested that GM-CSF induces accumulation and differentiation of antigen-presenting cells, particularly dendritic cells that can initiate immunity. To evaluate this model in vivo, we performed i.m. and i.p. injections of an adenovirus vector encoding murine GM-CSF (Ad-mGM-CSF) and evaluated local and systemic effects. After intramuscular injection, local changes were characterized by the accumulation of myeloid cells, a subsequent infiltration of lymphocytes and then myonecrosis. Intraperitoneal injection also induced an accumulation of myeloid cells, an increase in CD3-positive T and a decrease in B220-positive B lymphocytes. Expression of the dendritic cell marker CD11c on 48 +/- 9% of the peritoneal cells (n = 6) along with high levels of surface MHC class II, a characteristic morphology, and endocytosis of FITC-dextran suggested in vivo differentiation of dendritic cells after i.p. injection of Ad-mGM-CSF. Systemic effects were observed after i.m. and i.p. injection of Ad-mGM-CSF. All mice developed hepatosplenomegaly resulting from extramedullary haematopoiesis. These changes were specific to GM-CSF as they were not seen in mice injected with an adenovirus vector without a transgene. Our observations indicate that adenoviral transfer of GM-CSF is a powerful tool for inducing local and systemic expansion of haematopoietic cells. The local expansion of myeloid cells displaying signs of dendritic cell differentiation, as characterized for the peritoneal cell compartment, can explain the potency of GM-CSF when used as an adjuvant in genetic immunotherapy.
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PMID:Local and systemic effects after adenoviral transfer of the murine granulocyte-macrophage colony-stimulating factor gene into mice. 1075 24

Reactive haemophagocytic syndrome is characterized by activation and uncontrolled non-malignant proliferation of T lymphocytes and macrophages, leading to a cytokine overproduction, which accounts for the main biological signs. Children usually present with an acute febrile illness, fulminant pancytopenia and hepatosplenomegaly, posing a problem of differential diagnosis with severe sepsis. Hemopoietic cells are actively ingested by monocytes/macrophages in various organs, including lymph nodes, bone marrow, liver and spleen. This exarcerbation of the histiocytic system is currently classified among the reactional histiocytoses. It reflects an inappropriate host immune response. Most patients have a known underlying disease (hemopathy, lupus, systemic juvenile arthritis, HIV infection). In the few cases that occur in the apparent absence of any risk factors, investigations should be made to look for predisposing inherited diseases, such as familial lymphohistiocytosis or Purtilo's disease in boys. The treatment rests on immunosuppressive agents, followed by bone marrow transplantation, which can provide a definitive cure in genetic forms.
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PMID:[Reactive hemophagocytic syndrome in children]. 1076 6

Haemophagocytic syndromes (HS) are the clinical manifestation of an increased macrophagic activity with haemophagocytosis. Pathophysiology is related to a deregulation of T-lymphocytes and excessive production of cytokines. The main clinicobiological features are fever, hepatosplenomegaly, adenopathies, skin rash, neurological features, cytopenias, hypertriglyceridaemia, hyperferritinaemia and coagulopathy. Diagnosis is based on examination of the bone marrow which shows benign histiocytes actively phagocytosing haemopoietic cells. Acquired HS are mostly associated with an underlying disease such as immunodeficiency, haematological neoplasias and autoimmune diseases. Infection-associated HS was originally described by Risdall in 1979, in viral disease. Since the initial description HS has also been documented in patients with bacterial, parasitic or fungal infections. Epstein-Barr virus (EBV) is the causative agent in most cases. In EBV-associated HS, which sometimes has a fatal course, unregulated T-cell reaction or uncontrolled B-cell proliferation may release cytokines. Management of HS consists of early diagnosis, careful screening for, and prompt treatment of, infections and detection and therapy of any underlying disease. Prognosis of infection-associated haemophagocytic syndrome (IAHS) is better than that in other types of secondary HS. Management of cytokine imbalance should be useful to improve the outcome and reduce the mortality rate in these cases.
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PMID:Haemophagocytic syndrome associated with infections. 1094 19

We describe a 21-year old man who was diagnosed as having adult onset Still's disease (AOSD) in association with isotretinoin treatment for acne conglobata. The patient was febrile, with a macular salmon pink rash, arthritis, hepatosplenomegaly, and axial lymphadenopathy. Laboratory results showed leukocytosis, mild liver dysfunction and negative rheumatoid factor and antinuclear antibodies. Isotretinoin, an orally active derivative of vitamin A, has been associated with various rheumatologic conditions such as arthralgia, myalgia, vasculitis and arthritis. The etiology of rheumatic disorders associated with retinoids is still obscure; however, it is presumed that immunomodulation by several mechanisms (such as an alteration of the cytokine balance) is probably ascribable to this interesting association.
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PMID:Isotretinoin-induced adult onset Still's disease. 1107 5

Glycogen storage disease (GSD) is a rare autosomal-recessive disorder characterized by hypoglycemia, hepatosplenomegaly, seizures, and failure to thrive in infants. Neutropenia and/or neutrophil dysfunction develops in GSD1b, but not in other types. GSD1b results from a deficiency of the glucose-6-phosphate translocase enzyme and the genetic defect maps to chromosome 11q23. Patients with GSD1b are susceptible to recurrent bacterial infections, commonly involving the perirectal area, ears, skin, and urinary tract, although life-threatening infections, such as septicemia, pneumonia, and meningitis occur less frequently. Although the exact mechanism of neutropenia in patients with GSD1b is not known, treatment with recombinant human granulocyte colony-stimulating factor (G-CSF) has reduced the incidence of infections and has improved the quality of life of these patients. Defects in neutrophil chemotaxis and intracellular bacterial killing have been described and appear to be corrected by the use of G-CSF. To date, no cases of myelodysplasia or acute myeloid leukemia have been observed in patients with GSD1b treated with G-CSF. A significant complication of cytokine therapy is the development of hypersplenism, requiring either a reduction in the dosage of G-CSF or splenectomy.
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PMID:Glycogen storage disease. 1195 92

We report here three cases of peripheral T-cell lymphoma unspecified (PTCL-US), which presented with bone marrow infiltration and hepatosplenomegaly and were successfully treated with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (auto-PBSCT). The patients were all characterized by cytokine-induced symptoms such as fever, anasarca, cytopenia, poor general condition, and disseminated intravascular coagulation syndrome. Laboratory data showed extremely high levels of soluble interleukin-2 receptor, beta(2)-microglobulin, and ferritin. All three patients were negative for anti-adult T-cell leukemia antibody. In one patient, hemophagocytosis was revealed by a histological examination of the bone marrow. The International Prognostic Index was high for all three patients, and they all achieved complete remission after the intensive chemotherapy for remission induction. During complete remission, they were treated with HDCT [modified interleukin-converting enzyme regimen] followed by auto-PBSCT. The recovery of hematopoiesis after auto-PBSCT was prompt and sustained engraftment was obtained. No serious adverse effects other than myelosuppression were noted. One patient died due to cerebrovascular disease without relapse 18 months after auto-PBSCT. The other two patients are still alive and have not suffered from relapse. Our observations suggest that auto-PBSCT following HDCT may be an effective and safe therapeutic modality for high-risk PTCL-US patients characterized by hepatosplenomegaly and cytokine-induced syndrome.
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PMID:High-dose chemotherapy and autologous peripheral blood stem cell transplantation for treatment of unspecified peripheral T-cell lymphoma presented with hepatosplenomegaly and hypercytokinemia syndrome: report of three cases. 1242 41

Schoolchildren from 2 areas of Kenya, Kangundo and Kambu, have contrasting prevalences of hepatosplenomegaly, despite having similar prevalences and intensities of Schistosoma mansoni infection. However, in individual children, S. mansoni infection intensity is positively correlated with organomegaly. In a previous study, hepatosplenomegaly was associated with Th1-type anti-schistosome cytokine responses. Although the high-morbidity Kambu area had higher malaria transmission than did low-morbidity Kangundo, hepatosplenomegaly was not associated with clinical malaria or with patent malarial parasitemia. However, chronic exposure to malaria might be involved. Here, retrospectively, we assayed plasma from this original study, for anti-Plasmodium falciparum and anti-S. mansoni antibodies, to test whether greater exposure to Plasmodium was a cofactor for hepatosplenomegaly. We found that hepatosplenic children had significantly higher levels of anti-P. falciparum antibodies, compared with nonhepatosplenic children, a finding that strongly suggests that some experience of P. falciparum influenced the development of hepatosplenomegaly in these S. mansoni-infected children.
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PMID:Associations between anti-Schistosoma mansoni and anti-Plasmodium falciparum antibody responses and hepatosplenomegaly, in Kenyan schoolchildren. 1269 17

Macrophage activation syndrome is due to macrophage stimulation secondary to excessive cytokine secretion. Infectious (mainly viral) and neoplastic (lymphomas primarily) diseases are the mainly triggering circumstances of this syndrome associated with immunodepression. Signs are fever, hepatosplenomegaly, lymphadenopathy, cytopenia, deranged liver function increases level of lactate dehydrogenase, triglyceridemia and serum ferritin. Diagnosis is established by the presence of cellular phagocytosis by macrophage on medullary or hepatic biopsy. It is a potentially life threatening condition. Treatment of the triggering circumstance associated with corticosteroids, chemotherapy (etoposide) or intravenous immunoglobulins, according to etiology, are necessary.
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PMID:[Macrophage activation syndrome]. 1529 67

Leishmaniasis is a zoonosis caused by an intracellular parasite belonging to the genus Leishmania. In Europe, Africa, South America and China, visceral leishmaniasis is caused by L. infantum. The vectors of leishmaniasis are phlebotomine sandflies belonging to the genera Phlebotomus. According to the World Health Organization there are 2 million new cases each year and 1/10 of the world's population is at risk of infection. Leishmaniasis is considered a zoonosis and human are generally accidental hosts. The animal reservoir includes rodents, dog and other mammals. Several studies have indicate that half of the dogs with antileishmanial antibodies have no signs of disease although, animal with subclinical infections are potentially infectious to sand flies. The factors determining susceptibility or resistence to visceral leishmaniasis remain unclear, but the genetics of the host may play a major role. Clinical signs are: intermittent fever, hepatosplenomegaly, skin lesions and ulcers, alopecia, onychogryphosis, anemia, thrombocytopenia and hypergammaglobulinemia. In mice, the outcome of infection depends on the polarized activation of one of two subsets of CD4+ T cells, Th1 or Th2, the subdivision into Th1 and Th2 cells is based on the pattern of cytokines that they produce. Th1 cells produce gamma interferon (IFN-gamma) and interleukin -2 (IL-2), whereas Th2 cells produce IL-4, IL-5, and IL-10. An important difference between susceptible and resistant mice is that the resistant mice are able to switch to a Th1 profile and control the disease. An important factor in the "decision" to form a Th1 or Th2 phenotype is the early cytokine environment, and IL-12 is one of the cytokines that contributes significantly to the establishment of the Th1 phenotype. Canine leishmaniosis is endemic in the Mediterranean basin and, in most cases is caused by the parasite Leishmania infantum. The main clinical findings are skin lesions, local or generalized lymphoadenopathy, loss of body weight, glomerulopathy, ocular lesions, epistaxis and lameness. Non pruritic skin lesions are the usual manifestation and several forms have been described, such as exfoliative dermatitis and alopecia, and ulcerative, nodular and pustular dermatitis. Seroepidemiological studies of canine leishmaniasis have revealed a large number of asymptomatic seropositive animals. Moreover in areas where leishmaniasis is highly endemic, high proportion of apparently healthy animals show low levels of anti-Leishmania antibodies. Others have regressive forms of the desease, and their antibody levels will decrease in the following months or years; still others maintain low levels of antibodies without developing the desease for many years. However, the total number of infected animals is unknown. Canine leishmaniasis is a major zoonosic parasitic disease, enzootic in the Mediterranean area, caused by the intracellular protozoan Leishmania infantum. The dog is the main reservoir host of the parasite. However, most infected dogs do not present any clinical signs, and there is evidence that Leishmania infection prevalence rates in areas of endemicity are higher than those ascertained by serological studies. Visceral leishmaniasis is becoming a real problem of public health because it is an opportunistic infection in immunocompromised patients and in human immunodeficiency virus-positive subjects. The detection of the extent of the infection, particularly among asymptomatic dogs, is of great importance for the control of leishmaniasis. PCR has been applied successfully in recent years to detect Leishmania spp. even in the cases with any of the clinical manifestation of leishmaniasis. Very recently, real-time PCR for Leishmania has been applied to evaluate the parasitic load of dog tissues both at the time of the diagnosis and during follow-up of the therapy and to measure cytokine mRNA levels in different clinical samples of infected and uninfected dogs.
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PMID:[Interpretation of laboratory data during cryptic leishmaniasis in dog]. 1530 23

Primary MDS is a group of heterogenous clonal haematopoetic disorders. In a third of patients MDS terminates as acute myeloid leukaemia, usually resisitant to treatment, while the others succumb due to infections and haemorrhage. Conservative managements of MDS (chemotherapy, haematopoetic growth factors, modulation of cytokine network) are unsuccessful, while the bone marrow transplantation is the only definite treatment. We reviewed clinical and haematological presentations, frequency of dysplastic features, histological and cytogenetic findings in 29 children with primary MDS. Indications for haematological evaluation in our patients were symptoms and signs of isolated or combined cytopenias, fever of unknown origin and frequent infections. Hepatosplenomegaly was found in 19 (65%) patients, while this pattern was found in 10% of adult patients. Normochromic anaemia was found in 25 (86%) patients and thrombocytopenia in 23 (76%). Patients presenting pancytopenia had the lowest probability of survival. Degree of dysplasia, histology and kariotype of bone marrow had no influence on survival rates. Prognostic factors in paediatric MDS are of limited significance, as MDS in children is an absolute indication for bone marrow transplantation.
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PMID:[Primary myelodysplastic syndrome in children]. 1563 84


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