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

We report an 18-year-old boy with common variable immunodeficiency who presented with splenomegaly as well as left axillary and lateral cervical lymphadenopathy. Main laboratory investigations showed severe thrombocytopenia. Epstein-Barr virus (EBV) DNA was detected in the patient's throat-washing specimens and lymph node biopsy. Lymphocytes from the lymph node biopsy were also positive for EBV nuclear antigen. Serology for EBV and cytomegalovirus was negative. A therapeutic attempt with acyclovir did not influence the course of infection. Six months' treatment with human lymphoblastoid interferon-alpha (IFN alfa) brought about the normalization of clinical and hematologic conditions. Detection on throat-washing specimens carried out 1 year after therapy was negative. Our preliminary experience suggests that human lymphoblastoid IFN-alpha is a valid alternative in therapy of immunodeficient EB virus-infected patients.
 ...
PMID:Effect of interferon-alpha therapy in a patient with common variable immunodeficiency and chronic Epstein-Barr virus infection. 851 35

In patients with common variable immunodeficiency (CVI), we have previously defined a subgroup of patients (CVIHyper) characterized by decreased numbers of CD4+ lymphocytes in peripheral blood, splenomegaly, and persistent immune activation in vivo, particularly of monocytes/macrophages. To further characterize this hyperactivity, parameters of activation of the tumor necrosis factor (TNF) system (TNF alpha and soluble TNF receptors [sTNFRs]) were measured in 24 patients with CVI and 20 healthy controls. Patients with CVI had significantly higher serum levels of TNF alpha and both types of sTNFRs, with the highest levels in the CVIHyper subgroup. In vitro, peripheral blood mononuclear cells (PBMC) and purified monocytes from CVIHyper patients spontaneously released significantly higher levels, and, after lipopolysaccharide (LPS) stimulation, significantly lower levels of TNF alpha and soluble p75-TNFR than cells from both other CVI patients and healthy controls. CVIHyper patients also had significantly higher TNF alpha:sTNFRs ratios in both serum and in unstimulated PMBC supernatants. The present study demonstrates persistent in vivo activation of the TNF system in CVI, particularly in the CVIHyper subgroup. This activation may contribute to the pathogenesis of both clinical and immunologic manifestations in CVI.
 ...
PMID:Persistent activation of the tumor necrosis factor system in a subgroup of patients with common variable immunodeficiency--possible immunologic and clinical consequences. 855 90

The scarcity of reported cases of paracoccidioidomycosis and AIDS remains unexplained. We review the details of the 27 cases reported in the medical literature. Paracoccidioidomycosis occurs in patients with advanced AIDS who are not receiving prophylaxis for Pneumocystis carinii pneumonia with trimethoprim-sulfamethoxazole, which is also effective against Paracoccidioides brasiliensis. Clinical manifestations include prolonged fever, weight loss, generalized lymphadenopathy, splenomegaly, hepatomegaly, and skin rash. Diagnosis can often be made by direct microscopic examination and culture of the fungus from skin and lymph node specimens and occasionally from sputum, blood, spinal fluid, and bone marrow specimens. Since antibodies to P. brasiliensis are occasionally detected, the diagnosis should not be ruled out for patients whose serology is negative. Despite specific therapy with different regimens, the overall mortality of paracoccidioidomycosis among patients with AIDS is high (30%). The prognosis can be improved by earlier diagnosis and aggressive therapy with amphotericin B, followed by lifelong immunosuppressive therapy with trimethoprim-sulfamethoxazole. Health care providers caring for human immunodeficiency virus-infected patients who live or have resided in areas in which paracoccidioidomycosis is endemic must be aware of the possibility that this systemic mycosis may occur and have potentially severe consequences.
 ...
PMID:Paracoccidioidomycosis and AIDS: an overview. 878 43

Infection of genetically susceptible C57BL/6 mice with the LP-BM5 isolate of murine retroviruses cause profound splenomegaly, hypergammaglobulinemia, lymphadenopathy, and an immunodeficiency syndrome which includes the development of terminal B-cell lymphomas. Because many of these and the other manifestations of LP-BM5 virus-induced disease are similar to those seen in AIDS, this syndrome has been named murine AIDS, or MAIDS. Previous reports have shown that the onset of MAIDS depends on the presence of both CD4+ T cells and B cells and have suggested that CD4+ T-cell-B-cell interactions are important to disease pathogenesis. Here, we assessed the possibility that interactions between CD40 and its ligand on activated CD4+ T cells, CD40 ligand/gp39, are involved in the development of MAIDS. To test this hypothesis, LP-BM5-infected B6 mice were treated in vivo with anti-gp39 monoclonal antibody. As a result, MAIDS-associated splenomegaly, hypergammaglobulinemia, germinal center formation, and the loss of in vitro responsiveness to the T- and B-cell mitogens concanavalin A and lipopolysaccharide were inhibited. Anti-gp39 monoclonal antibody-treated LP-BM5-infected mice were also able to mount essentially normal alloantigen-specific cytolytic T-lymphocyte responses. These results support the possibility that molecular interactions between CD40 and gp39 are critical to the development of MAIDS.
 ...
PMID:Antibody to the ligand for CD40 (gp39) inhibits murine AIDS-associated splenomegaly, hypergammaglobulinemia, and immunodeficiency in disease-susceptible C57BL/6 mice. 864 87

A 40 year old white woman with common variable immunodeficiency of four years duration presented with rapidly increasing splenomegaly. Despite high dose, weekly intravenous immunoglobulin, it was impossible to raise the trough serum IgG concentration to within the normal range. While waiting for a diagnostic splenectomy, low dose corticosteroids were started, leading to a decrease in the size of the spleen and an increase in the trough IgG concentration. Both spleen and liver showed non-caseating granulomas. Following splenectomy, the corticosteroids were tailed off and the trough IgG was maintained well into the normal range on a reduced, fortnightly dose of intravenous immunoglobulin and a low dose of oral corticosteroid.
 ...
PMID:Granulomatous disease in common variable immunodeficiency: effect on immunoglobulin replacement therapy and response to steroids and splenectomy. 870 66

Clinical characteristics associated with bacillary angiomatosis and bacillary peliosis (BAP) in patients with human immunodeficiency virus (HIV) infection were evaluated in a case-control study; 42 case-patients and 84 controls were matched by clinical care institution. Case-patients presented with fever (temperature, > 37.8 degrees C; 93%), a median CD4 lymphocyte count of 21/mm3, cutaneous or subcutaneous vascular lesions (55%), lymphadenopathy (21%), and/or abdominal symptoms (24%). Many case-patients experienced long delays between medical evaluation and diagnosis of BAP (median, 4 weeks; range, 1 day to 24 months). Case-patients were more likely than controls to have fever, lymphadenopathy, hepatomegaly, splenomegaly, a low CD4 lymphocyte count, anemia, or an elevated serum level of alkaline phosphatase (AP) (P < .001). In multivariate analysis, a CD4 lymphocyte count of < 200/mm3 (matched odds ratio [OR], 9.9; P < .09), anemia reflected by a hematocrit value of < 0.36 (OR, 19.7; P < .04), and an elevated AP level of > or = 2.6 mukat/L (OR, 23.9; P < .05) remained associated with disease after therapy with zidovudine was controlled for. BAP should be considered an AIDS-defining opportunistic infection and should be included in the differential diagnosis for febrile, HIV-infected patients with cutaneous or osteolytic lesions, lymphadenopathy, abdominal symptoms, anemia, or an elevated serum level of AP.
 ...
PMID:Bacillary angiomatosis and bacillary peliosis in patients infected with human immunodeficiency virus: clinical characteristics in a case-control study. 872 33

Rationally designed synthetic inhibitors of retroviral proteases inhibit the processing of viral polypeptides in cultures of human T lymphocytes infected with human immunodeficiency virus type 1 (HIV-1) and therefore suppress the infectivity of HIV-1 in vitro. We have previously reported the antiviral activity in vitro of HIV-1 protease inhibitors against the C-type retrovirus Rauscher murine leukemia virus (RMuLV) and the lentivirus simian immunodeficiency virus (SIV). The same compounds which blocked the infectivity of HIV-1 also inhibited the infectivity of RMuLV and SIV in vitro. This report extends these findings by testing the antiviral activity of HIV-1 protease inhibitors in vivo in the RMuLV model. RMuLV-infected mice were treated twice a day (bid) with either an active (SKF 108922) or inactive (SKF 109273) compound for fourteen days by the intraperitoneal (i.p.) route. Compared with excipient control, SKF 108922, formulated with hydroxypropyl-beta-cyclodextrin (HPB), reduced virus-induced splenomegaly, viremia, and serum reverse transcriptase (RT) levels, while SKF 109273 was inactive. The HPB vehicle by itself enhanced replication of RMuLV. The effects of changing the formulation and the route of administration were examined. SKF 108922, formulated in HPB, had similar antiviral activity when administered by the i.p. or subcutaneous (SC) routes. However, SKF 108922 administered as a colloidal suspension in cholesterol sulfate (CS) had no detectable antiviral effect. Measurements of the circulating levels of the protease inhibitor in plasma explained this result. Plasma concentrations of SKF 108922 exceeded 1000 nM within 10 min after SC administration of the compound solubilized in HPB, but SKF 108922 was not detected in plasma after SC administration of the same dose formulated with CS. Information on optimal conditions for administering these agents should prove useful in guiding their clinical application Therefore, RMuLV should provide a good model for the preclinical evaluation and development of this class of agents for the treatment of HIV.
 ...
PMID:Effects of SKF 108922, an HIV-1 protease inhibitor, on retrovirus replication in mice. 873 97

Murine AIDS (MAIDS) induced by infection of C57BL/6 mice with a mixture of retroviruses known as LP-BM5 is characterized by lymphadenopathy, splenomegaly, and T and B cell dysfunction. By labeling with bromodeoxyuridine in vivo, we found vigorous CD4 T cell proliferation during the initial stages of infection, yet a loss in their ability to function both in vivo and in vitro. In addition, a significant fraction of the CD4 T cell population in infected mice undergoes spontaneous apoptosis in vivo. Upon in vitro stimulation with anti-CD3 plus PMA, anergic CD4 T cells from mice with MAIDS fail to progress through the cell cycle (G0/G1 arrest), and a fraction of the cells undergoes apoptosis. The addition of IL-2 along with TCR-mediated stimulation not only fails to rescue CD4 T cells from apoptosis, but enhances activation-induced cell death. To further understand the regulation of the suicide pathway(s) of anergic CD4 T cells vs the cytokine synthesis pathway(s) of normal CD4 T cells, we evaluated their expression of Bcl-2 protein. As infection progresses, the expression of Bcl-2 among CD4 T cells declines and drops further when CD4 T cells are restimulated through the TCR in vitro. These results suggest that this CD4 T cell immunodeficiency in MAIDS includes a TCR-induced program of activation-induced cell death and an uncoupling from cytokine synthesis pathways and proliferation of CD4 T cells. The decline in Bcl-2 expression may be in part responsible for this reprogramming.
 ...
PMID:TCR triggering of anergic CD4 T cells in murine AIDS induces apoptosis rather than cytokine synthesis and proliferation. 875 10

An Ethiopian immigrated to Israel and gave a positive test result for human immunodeficiency virus. Soon after, he was thrice admitted to hospital in 3 months for severe pneumonia. Acquired immunodeficiency syndrome was diagnosed, as was hyperreactive malarial splenomegaly (HMS). Thereafter, during maintained proguanil treatment for HMS, the patient remained well for 16 months. Then, after another pneumonic illness, pneumococcal vaccine was administered. Proguanil was maintained for another 10 months and, despite declining CD4 cell counts, good health continued for a further 18 months.
 ...
PMID:Hyperreactive malarial splenomegaly and AIDS: proguanil prevents recurrent pneumonia. 875 89

Lipophilic ester prodrugs of 9-(2-phosphonylmethoxyethyl)adenine (PMEA), i.e., bis(pivaloyloxymethyl)-PMEA [bis(POM)-PMEA] and diphenyl-PMEA, have been synthesized in an attempt to increase the oral bioavailability of this broad-spectrum antiviral agent. The antiretroviral efficacy was determined in severe combined immune deficiency (SCID) mice infected with Moloney murine sarcoma virus (MSV). They were treated twice daily for 5 days after infection. Oral treatment with bis(POM)-PMEA at a dose equivalent to 100 or 50 mg of PMEA per kg of body weight per day proved markedly effective in delaying MSV-induced tumor formation and death of the mice. Oral bis(POM)-PMEA afforded anti-MSV efficacy equal to that of subcutaneous PMEA given at equimolar doses. Oral treatment with PMEA or diphenyl-PMEA proved less efficient. Similarly, in mice infected with Friend leukemia virus (FLV), oral treatment with bis(POM)-PMEA at a dose equivalent to 100 or 50 mg of PMEA per kg per day effected a marked inhibition of FLV-induced splenomegaly (87 and 48% inhibition, respectively), the efficacy being equal to that of PMEA given subcutaneously at equivalent doses. Pharmacokinetic experiments with mice showed that the oral bioavailabilities of PMEA following oral gavage of bis(POM)-PMEA, diphenyl-PMEA, or PMEA (at a dose equivalent to 50 mg of PMEA per kg) were 53,3, and 16%, respectively. These data were calculated from the levels of free PMEA in plasma. Also, the recoveries of free PMEA in the urine upon oral administration of bis(POM)-PMEA, diphenyl-PMEA, or PMEA (at a dose equivalent to 25 mg of PMEA per kg) were 48, 4, and 7%, respectively. Oral bis(POM)-PMEA was not recovered from plasma, suggesting that it was readily cleaved to free PMEA. In contrast, diphenyl-PMEA was not efficiently cleaved to free PMEA, resulting in a rather low oral bioavailability of PMEA from this prodrug. Bis(POM)-PMEA appears to be an efficient oral prodrug of PMEA that deserves further clinical evaluation in human immunodeficiency virus-infected individuals.
 ...
PMID:Antiretroviral activity and pharmacokinetics in mice of oral bis(pivaloyloxymethyl)-9-(2-phosphonylmethoxyethyl)adenine, the bis(pivaloyloxymethyl) ester prodrug of 9-(2-phosphonylmethoxyethyl)adenine. 878 73


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>