Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first case of Q fever endocarditis that has been diagnosed in Mexico is presented. A 10-year-old girl with discrete subaortic stenosis (SAS) and patent ductus arteriosus (PDA) was seen in December of 1996 with fever, hepatomegaly and splenomegaly. She presented also anemia, leukopenia, hypergammaglobulinemia, positive rheumatoid factor, cryoglobulinemia, antinuclear and anticytoplasmic antibodies (anti-RNA-proteins and anti-DNA). An aortic valve vegetation was seen by echocardiogram. Blood-cultures were negative. Antibody test for Coxiella burnetii was positive. Treatment with doxicyclin was initiated as soon the diagnosis was done. PDA was closed, SAS was liberated and two aortic vegetations were resected. Endocarditis in Q fever occurs when there is predisposing heart disease and/or immunodeficiency. Effective therapy has not yet been established. The diagnosis of Q fever endocarditis is difficult; it should be considered, in case of clinical suspicion of endocarditis with negative blood-cultures.
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PMID:[Coxiella burnetii endocarditis. A report of the first case diagnosed in Mexico]. 981 Mar 69

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by chronic, histologically benign splenomegaly and generalized lymphadenopathy, hypergammaglobulinemia, and autoantibody formation. ALPS has been attributed to defective programmed cell death of lymphocytes, most often arising as a result of mutations in the gene encoding the lymphocyte apoptosis receptor Fas/APO-l/CD95. We identified a novel mutation in the intracellular apoptosis signaling domain of Fas in 11 members of a family, individual members of which have been monitored for up to 25 years, with 1 or more features of ALPS. This study of a large number of family members carrying the same Fas defect demonstrates that ALPS is inherited in an autosomal dominant fashion but with a high degree of variability in clinical expression. Although 1 affected individual died of postsplenectomy sepsis and 1 has been treated for lymphoma, the Fas mutation in this family has been compatible with a healthy adulthood, as clinical features of ALPS have receded with increasing age.
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PMID:The clinical spectrum in a large kindred with autoimmune lymphoproliferative syndrome caused by a Fas mutation that impairs lymphocyte apoptosis. 982 19

We describe a 17 year old patient suffering from Canale-Smith syndrome (CSS) including chronic lymphadenopathy, splenomegaly, hypergammaglobulinemia and recurrent Coombs positive hemolytic crises. The parents are not consanguine, all other family members including two brothers are healthy. Peripheral blood mononuclear cells of the patient showed an increased rate of CD3 positive, CD4/CD8 double negative T-lymphocytes. In vitro assays showed these cells to have an increased rate of spontaneous apoptosis. Though expression of Fas/Apo-1 (CD95) and Fas-ligand (FasL) was detected on RNA- and protein level we found Fas/Apo-1 mediated apoptosis being significantly reduced. Sequencing of the fas/apo-1 gene proved the patient RT and his father to carry a point mutation at position 804 located in exon 9 (death domain) leading to an amino acid substitution. For developing of CSS, a fas/apo-1 mutation seems to be necessary but not sufficient. An additional independent mechanism must be involved in the pathogenesis of human lpr<-phenotype.
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PMID:Increased spontaneous in vitro apoptosis in double negative T cells of humans with a fas/apo-1 mutation. 1020 May 34

Macrophages play a key role in AIDS pathogenesis and thus controlling infectivity and viral replication in these cells is a key issue in any antiretroviral therapy. In the present study, using a murine model of AIDS, we evaluated new therapeutic approaches specifically designed for the protection of macrophages. Based on previous observations, we took advantage of the unique ability of autologous erythrocytes to deliver drugs selectively to macrophages. The antiviral drugs selected were a new homodimer of AZT (AZTp2AZT) and reduced glutathione (GSH). The addition of an oral drug for the protection of lymphocytes (i.e., AZT) was also investigated. C57BL/6 mice infected with the retroviral complex LP-BM5 were treated with GSH-loaded erythrocytes, GSH-loaded erythrocytes plus oral AZT, or GSH/AZTp2AZT-loaded erythrocytes plus oral AZT. The treatments including AZT and erythrocytes loaded with GSH alone or with GSH plus AZTp2AZT provided similar results and were most effective in inhibiting the progression of MAIDS; they reduced splenomegaly, lymphadenopathy, and hypergammaglobulinemia by about 70%, 90% and 83%, respectively, when compared with infected animals at 10 weeks postinfection. Evaluation of BM5d proviral DNA content in infected organs revealed that both treatments were able to almost completely protect most infected animals. They were also able to normalize the blood lymphocyte phenotype and to restore the responses of T and B cells to mitogens significantly. Treatment with GSH-loaded erythrocytes alone did not provide significant results for most parameters investigated, but a marked reduction in proviral DNA content was obtained in infected organs, including the brain. The results reported in this paper confirm the important role of macrophages in retroviral infection and moreover prove that erythrocytes, by selectively protecting these cells, strongly affect MAIDS progression. Furthermore, the combination of GSH- or GSH/AZTp2AZT-loaded erythrocytes with an oral nucleoside analogue (AZT) for the protection of lymphocytes provides additive responses in all the parameters investigated.
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PMID:Role of macrophage protection in the development of murine AIDS. 1036 Jul 98

Murine acquired immunodeficiency syndrome (MAIDS) is a complex immunopathology caused by a defective murine leukemia virus (LP-BM5) that mainly targets B-lymphocytes. Lymphadenophathy, splenomegaly, hypergammaglobulinemia and progressive immunodeficiency are prominent features of MAIDS. Previously, we showed that the ubiquitin proteolytic system was upregulated in infected lymph nodes [Crinelli, R., Fraternale, A., Casabianca, A. & Magnani, M. (1997) Eur. J. Biochem. 247, 91-97]. In this report, we demonstrate that increased 26S proteasome activity is responsible for accelerated turnover of the IkappaBalpha inhibitor in lymph node extracts derived from animals with MAIDS. The molecular mechanisms mediating IkappaBalpha proteolysis involved constitutive phosphorylation of IkappaBalpha at Ser32 and Ser36 and subsequent ubiquitination, suggesting persistent activation of an NF-kappaB inducing pathway. Interestingly, enhanced IkappaBalpha degradation did not result in enhanced NF-kappaB DNA binding activity, but rather in a different subunit composition. The modulation of NF-kappaB/IkappaB system may affect multiple immunoregulatory pathways and may in part explain the mechanisms leading to the profound immune dysregulation involved in MAIDS pathogenesis.
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PMID:Activation of the ubiquitin proteolytic system in murine acquired immunodeficiency syndrome affects IkappaBalpha turnover. 1042 5

MRL/Mpj-lpr/lpr (MRL/lpr) mice develop autoimmune disorders, including lymphoproliferation, glomerulonephritis, autoantibody production, and hypergammaglobulinemia. To investigate the role of the costimulatory molecule CD28 in the development of these disorders, MRL/lpr mice lacking CD28 were generated by gene targeting. Compared with CD28+/+ MRL/lpr mice, CD28-/- MRL/lpr mice showed decreased lymphadenopathy but increased splenomegaly associated with the expansion of abnormal B220+ TCRalphabeta+ T cells. Although levels of IgM Abs were unchanged in CD28-/- MRL/lpr mice, the production of anti-DNA IgG Abs and IgG rheumatoid factors were suppressed. IgG deposition in the glomeruli was markedly decreased, and the development of glomerulonephritis was significantly retarded. Furthermore, renal vasculitis and arthritis were absent in CD28-/- MRL/lpr mice. These results indicate that, although CD28 is not required for the generation of the abnormal T cell population in MRL/lpr mice, it does play an important role in the development of autoimmune disease in these animals.
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PMID:Role of the costimulatory molecule CD28 in the development of lupus in MRL/lpr mice. 1047 82

A simian homologue of Kaposi's sarcoma-associated herpesvirus (KSHV), the eighth human herpesvirus (HHV8), was isolated from a simian immunodeficiency virus (SIV)-infected rhesus macaque (Macaca mulatta) that developed a multicentric lymphoproliferative disorder (LPD). This simian rhadinovirus is genetically similar to a recently described rhesus rhadinovirus (RRV) (Desrosiers, R.C., V.G. Sasseville, S.C. Czajak, X. Zhang, K.G. Mansfield, A. Kaur, R.P. Johnson, A.A. Lackner, and J.U. Jung. 1997. J. Virol. 71:9764-9769) and is designated RRV 17577. RRV 17577 was experimentally inoculated into rhesus macaques with and without SIV(mac239) infection to determine if RRV played a role in development of the LPD observed in the index case. In contrast to control animals inoculated with SIV(mac239) or RRV alone, two animals coinfected with SIV(mac239) and RRV 17577 developed hyperplastic LPD resembling the multicentric plasma cell variant of Castleman's disease, characterized by persistent angiofollicular lymphadenopathy, hepatomegaly, splenomegaly, and hypergammaglobulinemia. Hypergammaglobulinemia was associated with severe immune-mediated hemolytic anemia in one RRV/SIV-infected macaque. Both RRV/SIV-infected macaques exhibited persistent RRV viremia with little or no RRV-specific antibody response. The macaques inoculated with RRV alone displayed transient viremia followed by a vigorous anti-RRV antibody response and lacked evidence of LPD in peripheral blood and lymph nodes. Infectious RRV and RRV DNA were present in hyperplastic lymphoid tissues of the RRV/SIV-infected macaques, suggesting that lymphoid hyperplasia is associated with the high levels of replication. Thus, experimental RRV 17577 infection of SIV-infected rhesus macaques induces some of the hyperplastic B cell LPDs manifested in AIDS patients coinfected with KSHV.
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PMID:Induction of B cell hyperplasia in simian immunodeficiency virus-infected rhesus macaques with the simian homologue of Kaposi's sarcoma-associated herpesvirus. 1049 21

In this article, we report the case of a 16-month-old German boy who was admitted to the Children's Hospital of Stuttgart with a 4-week history of intermittent fever, decreased appetite, weakness, fatigue, and difficulty sleeping. He was healthy at birth and remained so for the first 15 months of his life. On admission, physical examination showed enlarged cervical, axillary, and inguinal lymph nodes, as well as hepatosplenomegaly. Laboratory data revealed pancytopenia, elevated liver function tests, and hypergammaglobulinemia. Blood, stool, and urine culture results were negative. Viral infections and rheumatologic and autoimmune disorders were ruled out, but a positive titer for Leishmania antibodies was noted. In a liver and bone marrow biopsy, the amastigote form of the parasite could not be seen in cells. The promastigote form of Leishmania was found and the diagnosis of visceral leishmaniasis was made by combining the cultures of both the liver and the bone marrow biopsy material in 5 mL 0.9% saline on brain heart infusion agar, supplemented with defibrinated rabbit blood and incubated at 25 to 26 degrees C for 5 days. The parasite was identified by Southern blot analysis as Leishmania infantum. Specific therapy with the antimonial compound sodium stibogluconate with a dose of 20 mg/kg body weight was begun immediately. Within 4 days, the patient became afebrile. The side effects of treatment, including erosive gastritis, cholelithiasis, worsening hepatosplenomegaly, elevation of liver enzymes, pancreatitis, and electrocardiogram abnormalities, necessitated the discontinuation of treatment after 17 days. On discharge 4 weeks later, the patient was stabilized and afebrile with a normal spleen, normal complete blood count, normal gammaglobulins, and decreasing antibody titers to Leishmania. During the next 24 months, the patient experienced intermittent episodes of abdominal pain, decreased appetite, recurrent arthralgia, and myalgia. But at his last examination in January 1998, he was well; all symptoms mentioned above had disappeared. Because the child had never left Germany, nonvector transmission was suspected and household contacts were examined. His mother was the only one who had a positive antibody titer against Leishmania donovani complex. She had traveled several times to endemic Mediterranean areas (Portugal, Malta, and Corse) before giving birth to the boy. But she had never been symptomatic for visceral leishmaniasis. Her bone marrow, spleen, and liver biopsy results were within normal limits. Culture results and polymerase chain reaction of this material were negative. A Montenegro skin test result was positive, indicating a previous infection with Leishmania. Western blot analysis showed specific recognition by maternal antibodies of antigens of Leishmania cultured from the boy's tissue. Visceral leishmaniasis is endemic to several tropical and subtropical countries, but also to the Mediterranean region. It is transmitted by the sand fly (Phlebotomus, Lutzomyia). Occasional nonvector transmissions also have been reported through blood transfusions, sexual intercourse, organ transplants, excrements of dogs, and sporadically outside endemic areas. Only 8 cases of congenital acquired disease have been described before 1995, when our case occurred. In our patient, additional evaluation showed that the asymptomatic mother must have had a subclinical infection with Leishmania that was reactivated by pregnancy, and then congenitally transmitted to the child. Visceral leishmaniasis has to be considered in children with fever, pancytopenia, and splenomegaly, even if the child has not been to an endemic area and even if there is no evidence of the disease in his environment, because leishmaniasis can be transmitted congenitally from an asymptomatic mother to her child.
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PMID:Congenital transmission of visceral leishmaniasis (Kala Azar) from an asymptomatic mother to her child. 1054 91

The pathology caused by acute Babesia bovis infection is similar to that seen in severe human malaria caused by Plasmodium falciparum infection, which is related to dysregulated production of inflammatory cytokines and nitric oxide (NO). We have observed induction of NO, inducible nitric oxide synthase (iNOS) and inflammatory cytokines in macrophages by B. bovis. Furthermore, proliferation of lymphocytes from individuals never exposed to certain protozoal pathogens can be induced by crude protozoal parasite extracts. We have repeatedly observed stimulation of naive PBMC from cattle to antigenic extracts of Babesia bovis. Based on recent studies demonstrating the mitogenicity of bacterial and other non-vertebrate DNAs for murine B cells and macrophages, the mitogenic properties of B. bovis DNA were examined. B. bovis and E. coli DNAs induced proliferation of PBMC and purified B cells from non-exposed cattle. Stimulatory activity was reduced by DNase treatment and methylation with CpG methylase, indicating the presence of stimulatory non-methylated CpG motifs in the B. bovis genome. B. bovis and E. coli DNAs enhanced IgG secretion by cultured B cells, stimulating IgG1 and more strongly, IgG2. Several hexameric CpG immunostimulatory sequences (ISS) active for murine B cells were identified in an 11 kb fragment of B. bovis DNA. An oligodeoxyribonucleotide containing one of these (AACGTT), located in the rhoptry associated protein-1 (rap-1) open reading frame, stimulated B cell proliferation. These studies identify a potential mechanism by which protozoal parasites may modulate host immune responses, leading to consequences such as hypergammaglobulinemia and splenomegaly. These results also support the use of ISS as vaccine adjuvants to enhance Type 1 immune responses in cattle.
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PMID:Modulation of host immune responses by protozoal DNA. 1061 97

Tumor necrosis factor (TNF) and Fas ligand (FasL) play major roles in the homeostasis of the peripheral immune system. This becomes dramatically obvious in the absence of a functional FasL. Mice with such a deficiency develop a profound lymphadenopathy, splenomegaly, hypergammaglobulinemia, and strain-dependent systemic autoimmune disease, and succumb to premature death. It is consequently termed generalized lymphoproliferative disorder (gld). By contrast, TNF deficiency alone does not result in a striking phenotype. Thus, we sought to determine what role TNF might play in contributing to the gld phenotype by creating C57BL/6.gld.TNF(-/-) mice. Contrary to the expected outcome, mice deficient for both FasL and TNF had a substantially milder gld phenotype with regard to mortality, lymphoaccumulation, germinal center formation, and hypergammaglobulinemia. To confirm these data in a strain highly permissive for the phenotype, C3H/HeJ.gld and C3H.HeJ.lpr mice were treated with a TNF-specific monoclonal antibody. This transient neutralization of TNF also resulted in a significantly attenuated lymphoproliferative phenotype. We conclude that TNF is necessary for the full manifestation of the lymphoproliferative disorder, in particular playing a critical role in lymphoaccumulation. Most importantly, absence of TNF protects gld mice against premature death.
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PMID:Tumor necrosis factor sustains the generalized lymphoproliferative disorder (gld) phenotype. 1062 Jun 7


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