Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

During a 1-year period, 28 animals from a breeding colony of N:NIH(S)-bg-nu-xid mice were discovered to have rapidly enlarging subcutaneous swellings in the ventral, cervical, and axillary regions. Five of the mice also had hind limb paresis. Twenty-two of the mice were heterozygous nude females, five were homozygous nude males, and one was a homozygous nude female. All of the above mice were homo- or hemizygous for the beige and X-linked immunodeficiency mutations. The average age of the mice was 8.3 months. Generalized enlargement of the peripheral and internal lymph nodes was present at the time of necropsy examination. Other lesions commonly noted at necropsy included splenomegaly (15 mice), pale and thickened ventral lumbar spinal musculature (11 mice), and opaque, thickened meninges of the brain (10 mice). Histologic examination consistently disclosed infiltrates of neoplastic lymphoblasts in multiple tissues including lymph nodes, spleen, bone marrow, and meninges of the brain and spinal cord. The cells were positive for IgG on immunofluorescent staining, suggesting that the tumors were of B cell origin. The neoplasms observed in these mice have several similarities to tumors found in immunodeficient humans, suggesting that these mice may serve as useful animal models of lymphoma.
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PMID:Lymphoblastic lymphoma in a colony of N:NIH(S)-bg-nu-xid mice. 143 98

Disseminated histoplasmosis (DH) is recognized as an opportunistic infection in patients with the human immunodeficiency virus (HIV), especially in regions where histoplasmosis is endemic. At the Kansas University Medical Center 148 patients were hospitalized with the diagnosis of AIDS from December 1983 to March 1991; 23 of these patients (16%) had disseminated histoplasmosis. The charts of these 23 patients were reviewed. Clinical signs and symptoms included fever (91%), cough (65%), and weight loss (48%). Splenomegaly, hepatomegaly, or lymphadenopathy was present in 52% of all patients. Anemia (39%), leukopenia (65%), and thrombocytopenia (52%) were common, and 22% had pancytopenia. Diagnosis was made by peripheral smear examinations (organisms visualized on 7 of 22 smears [32%]), blood cultures (positive for H capsulatum in 16 of 20 patients, [80%]), bone marrow cultures (positive in 14 of 15 patients, [93%]), and bone marrow aspirate and biopsy examinations (organisms seen on 18 of 21 stains, [86%]). The combination of these four tests revealed the diagnosis of DH in 23 of 23 patients (100%). Induction and maintenance amphotericin B therapy was given to all but 2 patients, and currently 8 of the 23 are alive. DH is a common opportunistic infection in AIDS patients from regions endemic for histoplasmosis. When DH is suspected, a peripheral smear examination, blood cultures, bone marrow cultures and bone marrow aspirate and biopsy should be done to make the diagnosis, since suppression of the disease is possible with appropriate therapy.
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PMID:Disseminated histoplasmosis in patients with AIDS. 147 Sep 57

Imexon (4-imino-1, 3-diazabicyclo-(3.1.0)-hexan-2-one) a cyanoaziridine compound was studied in the treatment of the murine retrovirus-induced immunodeficiency disease model of AIDS (LP-BM5, MAIDS). Imexon, in dose-dependent fashion, partially prevented the development of hypergammaglobulinemia and splenomegaly, and partially prevented the decline in the phytohemagglutinin-induced proliferative response of spleen lymphocytes when started 1 or 15 days after virus inoculation. There was a statistically significant reduction in these disease-associated manifestations. When animals were treated starting 78 or 92 days after virus inoculation, lymphadenopathy was completely abrogated and survival was significantly prolonged in a dose-responsive manner. Since Imexon and other cyanoaziridine compounds have been safely administered to humans, we suggest that this class of compounds be further investigated in both large animal models of HIV infection and in patients with HIV-induced disease.
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PMID:Treatment of the murine, retrovirus-induced lymphoproliferative immunodeficiency disease (LP-BM5) in C57BL/10 mice with the immunomodulator Imexon. 151 14

High sequence variability in the envelope gene of human immunodeficiency virus has provoked interest in nonenvelope antigens as potential immunogens against retrovirus infection. However, the role of core protein antigens encoded by the gag gene in protective immunity against retroviruses is unclear. By using recombinant vaccinia viruses expressing the Friend murine leukemia helper virus (F-MuLV) gag gene, we could prime CD4+ T-helper cells and protectively immunize susceptible strains of mice against Friend retrovirus infection. Recovery from leukemic splenomegaly developed more slowly after immunization with vaccinia virus-F-MuLV gag than with vaccinia virus-F-MuLV env; however, genetic nonresponders to the envelope protein could be partially protected with Gag vaccines. Class switching of F-MuLV-neutralizing antibodies from immunoglobulin M to immunoglobulin G after challenge with Friend virus complex was facilitated in mice immunized with the Gag antigen. Sequential deletion of the gag gene revealed that the major protective epitope was located on the N-terminal hydrophobic protein p15.
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PMID:Protection against Friend retrovirus-induced leukemia by recombinant vaccinia viruses expressing the gag gene. 153 53

A number of nucleoside analogues are active against the infectivity of human immunodeficiency virus (HIV); however, their use is limited by toxic side effects and by limited phosphorylation in the infected cells. In an attempt to overcome these problems, a drug delivery system has been developed. A prototype of these drugs in a form already phosphorylated (2',3'-dideoxycytidine 5'-triphosphate; ddCTP) was encapsulated into erythrocytes. Subsequently, by the addition of Zn, an arrangement of band 3 in clusters was induced (band 3 is the major transmembrane protein in erythrocytes). The immune system recognizes these clusters as nonself, promoting autologous IgG binding and phagocytosis by cells of the monocyte-macrophage lineage. In this way, ddCTP encapsulated into erythrocytes was delivered to macrophage cells, where concentrations greater than 2 microM were found. Addition of ddCTP-loaded erythrocytes to macrophages previously infected by HIV-1 results in almost complete inhibition of HIV production over 3 weeks in culture. Administration of ddCTP-loaded erythrocytes to LP-BM5-infected mice at 10-day intervals over a period of 3 months results in reduction of lymphoadenopathy, splenomegaly, and hypergammaglobulinemia. Thus, the delivery of nucleoside analogues in phosphorylated form is feasible, and selective targeting to virus reservoirs (macrophage cells) can be accomplished by the use of autologous erythrocytes.
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PMID:Targeting antiretroviral nucleoside analogues in phosphorylated form to macrophages: in vitro and in vivo studies. 163 Nov 45

Serum neopterin levels were analysed in 43 patients with primary hypogammaglobulinaemia (25 common variable immunodeficiency (CVI), 12 congenital hypogammaglobulinaemia (CH), six X-linked hypogammaglobulinaemia (XLH)), and in 33 healthy controls. The neopterin values were correlated to lymphocyte subset counts in peripheral blood, lymphocyte mitogen responses and clinical and histological manifestations in the study group. Serum neopterin levels were significantly elevated in all subgroups of patients and particularly in the CVI groups where the highest concentrations were found (P less than 0.001, CVI versus controls). Furthermore, in CVI and CH patients elevated neopterin levels were strongly correlated to decreased number of CD4+ lymphocytes (rs = -0.61, P less than 0.005 and rs = -0.83, P less than 0.001, respectively). In the CVI group high neopterin levels were also significantly correlated to low number of circulatory B (CD19+) lymphocytes (rs = -0.58, P less than 0.05). Both patients with moderately and those with severely depressed lymphocyte mitogen responses had significantly higher neopterin levels than those with normal responses. In addition, high neopterin levels were significantly associated with the occurrence of splenomegaly and nodular intestinal lymphoid hyperplasia. The immunological findings were consistently observed in longitudinal testing, and appeared to be characteristic for the individual patient. High serum neopterin levels are thought to be a marker for hyperactivity in monocytes/macrophages, and dysfunction of these cells may therefore be associated with fundamental immune pathology in some subgroups of primary hypogammaglobulinaemia.
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PMID:Raised serum neopterin levels in patients with primary hypogammaglobulinaemia; correlation to other immunological parameters and to clinical and histological features. 163 65

Adult C57BL/10 mice (H-2b Fv-1b) inoculated with LP-BM5 murine leukemia virus develop a disease which has many features in common with human acquired immunodeficiency syndrome (AIDS), in particular abnormal lymphoproliferation and severe immunodeficiency. In the present study, we examined the possibility that this murine AIDS (MAIDS) model would be useful for evaluating antiretrovirus drugs in vivo through the use of a well-defined antiretrovirus drug, the reverse transcriptase (RT) inhibitor (H. Mitsuya, K.J. Weinhold, P.A. Furman, M.H. St. Claire, S. Nusinoff-Lehrman, R.C. Gallo, D. Bolognesi, D.W. Barry, and S. Broder, Proc. Natl. Acad. Sci. USA 82:7096-7100, 1985) 3'-azido-3'-deoxythymidine (AZT). We evaluated the effect of AZT treatment on de novo virus infection as well as on the induction of immunodeficiency by various parameters, including RT activity in serum, splenomegaly, proliferative responses against alloantigens and mitogens, soluble-antigen-presenting cell activity, and immunoglobulin G levels in serum. Our results demonstrated that AZT treatment of C57BL/10 mice infected with LP-BM5 murine leukemia virus efficiently prevented the induction of immunodeficiency if started at the time of virus inoculation. Starting AZT treatment 1 week later provided only a partial protective effect. Starting AZT treatment 2 weeks later was associated with suppression of RT activity in serum but no prevention of immunosuppression. This MAIDS model may allow rapid and cost-effective screening for antiretrovirus drugs targeted against retroviral functions shared between human AIDS and MAIDS, such as those encoded by gag, pol, or env.
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PMID:3'-Azido-3'-deoxythymidine prevents induction of murine acquired immunodeficiency syndrome in C57BL/10 mice infected with LP-BM5 murine leukemia viruses, a possible animal model for antiretroviral drug screening. 169 56

The present paper describes the clinical and laboratory follow-up of 11 patients with the diagnosis of common variable immunodeficiency. Their age varied from 8 to 45 years. The mean disease time was 12.6 years and mean diagnosis time 4.3 years. Infectious manifestations, mainly of the respiratory and digestive tracts, occurred in all patients. Polyadenomegaly was noted in seven, hepatomegaly in six, splenomegaly in five and arthralgia in four patients. All of them presented serum IgG less than 250 mg/dl. IgA less than 33 mg/dl and IgM less than 31 mg/dl, except one with IgM = 176 mg/dl. The isohaemagglutinin titers were less than 1/20 in all but one patient. The determination of the number of B lymphocytes in the peripheral blood revealed normal counts in three, elevated in one and decreased in five patients. The CD-4/CD-8 ratio was less than 1 in 8 and greater than 1 in three of them. Five patients had positive cutaneous late reactions to at least one of the following antigens: PPD, SK-SD (Varidase), Trichophytin and Levedurin (Candidin). A decrease of the proliferative activity of peripheral blood mononuclear cells stimulated by lectins (PHA, Con-A, PWM) was also noted. Natural killer function was decreased. The association a possible role of regulatory lymphocytes in the immunopathogenesis of this disease. The data presented here emphasize the diversity of clinical and immunological manifestations of this disease, which could be noted between diverse patients and in the follow-up of a single one. In our cases the disease had an evolutive character, with a primarily humoral dysfunction followed by cellular immunity disturbances that determined poorer prognosis and progressive difficulties in the therapeutics. We suggest a conceptual reevaluation of this condition and a new denomination, for instance "Late-Onset Combined Immunodeficiency". The long delay between the initial clinical manifestations of the disease and its diagnosis was a handicap for an adequate treatment. Early intervention could certainly decrease the morbidity and mortality of the disease.
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PMID:[Common variable immunodeficiency (hypogammaglobulinemia of late onset or acquired hypogammaglobulinemia): initial follow-up of 11 cases]. 172 73

The three non-allelic gld, lpr and mev mutations in the mouse all lead to profound immunodeficiency besides a splenomegaly and a generalized autoimmunity. Spleen cells from young B6 gld, B6 lpr and B6 mev mice all display a decreased proliferative response to the T-cell mitogen concanavalin A (ConA), but the nature of the deficiency seems very different. No restoration of proliferation could be obtained by adding exogenous recombinant rIL2 to ConA-treated mev spleen cells, this lack of IL2-responsiveness suggesting a lack of (functional) IL2-receptors. In young mice of both gld and lpr strains, a B6 wild-type level of proliferation could be reached by rIl2 addition to ConA-treated spleen cells, this normal responsiveness to exogenous IL2 suggesting a normal expression of IL2-receptors. The endogenous IL2 production by ConA-treated spleen cells decreased very much with ageing in both B6 gld and B6 lpr mice. Yet, IL2 production in young mice revealed an earlier deficiency of the B6 lpr mice: the young B6 gld IL2 levels reached about 60% of age-matched B6 wild cell levels, but the B6 lpr levels reached 14% only. Finally the addition of exogenous rIL2 to ConA-pretreated cells from old B6 gld and B6 lpr mice, while enhancing the proliferative responses, could not restore the B6 wild-type levels. This suggests that, with ageing, the expression of functional IL2-receptors may become as abnormal in these gld and lpr mutants as it is from birth in the mev mutant mice.
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PMID:Different nature of the proliferation defects of GLD, LPR and MEV C57BL/6 mouse lymphoid cells. 175 26

We observed 12 patients with acute human immunodeficiency virus type 1 (HIV-1) infection. The clinical syndrome was characterized by fever (all cases), generalized lymphadenopathy (11), arthralgias and myalgias (9), sore throat (9), rash (7), splenomegaly (6), and other less frequent signs and symptoms. All patients had a spontaneous resolution of their symptoms within 5-30 days. Anti-HIV-1 serum antibodies, as measured by enzyme immunoassay (EIA) at the onset of clinical illness, were negative in every patient. HIV antigen (p24), on the contrary, was detectable in nine cases. Western blot IgM and IgG analysis was serially performed: IgMs were positive in nine cases and IgGs in three. The CD4+/CD8+ ratio was low in all patients because CD8+ were remarkably increased and CD4+ slightly reduced. A laterocervical lymph nodes biopsy was performed in four patients. The morphological and immunohistological pattern of the acute HIV-1-related lymphadenopathy did not correspond to any of the typical ones. The envelope virus protein gp120/160 was found in interfollicular and follicular lymphocytes, in endothelial cells, and in interdigitating and dendritic reticulum cells. The p17 and p24 core virus proteins were mainly detected in endothelial, interdigitating, and dendritic reticulum cells, but in only a few lymphocytes. The follow-up suggests a rapid evolution to ARC and AIDS in patients showing an acute symptomatic HIV infection.
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PMID:Acute HIV-1 infection: clinical and biological study of 12 patients. 196 96


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