Disease relevance of Splenomegaly

• The three genotypes (+/+, +/-, -/-) showed mendelian segregation at birth (1:2:1) demonstrating that the absence of TC-PTP was not lethal in utero, but all homozygous mutant mice died by 3-5 wk of age, displaying runting, splenomegaly, and lymphadenopathy [1].
• Glomerular deposition of immune complexes (ICs), glomerulonephritis, and splenomegaly were observed in C4(-)(/)- but not Cr2(-)(/)- mice [2].
• Introduction of the transgene into the ob/ob background suppressed the obesity characteristic of this mutation; however, transgenic mutant mice developed severe hepato- and splenomegaly [3].
• Hemodynamic studies were performed in 5 vinyl chloride monomer workers in whom splenomegaly or thrombocytopenia was detected during a screening program at major chemical plant [4].
• A 35-yr-old man with moderate hypertriglyceridemia, associated with a positive family history for hyperlipidemia, developed chylomicronemia with abdominal pain, muscle pain, and splenomegaly while being treated with cimetidine for a duodenal ulcer [5].

Psychiatry related information on Splenomegaly

• A 40-year-old man with rheumatoid arthritis, splenomegaly and mild thrombocytopenia presented with gross ascites and a history of excess alcohol consumption [6].
• It was also demonstrated that IL-12 gene therapy, in contrast to the IL-12 protein therapy, was not associated with weight loss, splenomegaly, increased Ly6 antigen expression in the spleen, or visible signs of toxicity, such as fur ruffling and lethargy [7].

High impact information on Splenomegaly

• By contrast, analysis of aging cohorts of both loss- and gain-of-function Lyn mutant mice revealed that Lyn(-/-) mice develop splenomegaly, increased numbers of myeloid progenitors, and monocyte/macrophage (M phi) tumors [8].
• In addition, the mice lack NK cells, develop splenomegaly, and have T cells with an activated phenotype, phenotypes seen in IL-2 receptor beta chain-deficient mice [9].
• Lnk(-/-) mice are viable, but display marked changes in the hematopoietic compartment, including splenomegaly and abnormal lymphoid and myeloid homeostasis [10].
• In murine Schistosoma mansoni infections, schistosome-specific cross-reactive idiotypes (CRI) are present in the sera of mice with moderate splenomegaly syndrome (MSS) at 20 wk after infection [11].
• Neutralizing monoclonal antibody to VEGFR2 completely inhibited VEGF(165), but not Ang-1-induced mobilization and splenomegaly [12].

Chemical compound and disease context of Splenomegaly

• However, delta9-THC administered daily for 10 days significantly inhibited Friend leukemia virus-induced splenomegaly by 71% at 200 mg/kg as compared to 90.2% for actinomycin D [13].
• The immunostimulatory effect of adriamycin and C. parvum administered as a single agent or in combination was associated with significant splenomegaly [14].
• Only the active fragmented, pyridine residue and unfractionated preparations caused splenomegaly and prevented the secondary in vitro generation of CTL [15].
• Serum bilirubin concentration, histological stage on liver biopsy, age, and the presence of splenomegaly were independent predictors of a high risk of dying [16].
• 188 schoolchildren aged 10-15 living in a malaria endemic area along the Thai-Burmese border were matched for age, splenomegaly, and weight and were then randomly assigned to receive either doxycycline (adult equivalent of 100 mg daily) or chloroquine (adult equivalent of 300 mg base weekly) [17].

Biological context of Splenomegaly

• The virus from IS cells induced the splenomegaly and high hematocrit typical of Friend virus-induced erythroid disease in SIM mice [18].
• Young, nonleukemic hCG-PR x PU.1+/- mice developed splenomegaly because of the abnormal expansion of myeloid cells in their spleens. hCG-PR x PU.1+/- mice developed a typical APL syndrome after a long latent period, but the penetrance of disease was 84%, compared with 7% in hCG-PR x PU.1+/+ mice (P < 0.0001) [19].
• Therefore, the decrease in platelet counts observed in EPO-treated mice was not due to increased BV or to an enlarged spleen [20].
• The autoimmune/lymphoproliferative syndrome (ALPS) displays defective function of Fas, autoimmunities, lymphadenopathy/splenomegaly, and expansion of CD4/CD8 double-negative (DN) T cells [21].
• Lyn-deficient mice display a collection of hematopoietic defects, including autoimmune disease as a result of autoantibody production, and perturbations in myelopoiesis that ultimately lead to splenomegaly and myeloid neoplasia [22].

Anatomical context of Splenomegaly

• In these 2 patients and 12 previous patients with rheumatoid arthritis associated with expanded populations of immunophenotypically homogeneous large granular lymphocytes, neutropenia occurred in all 14, thrombocytopenia in 6, anemia in 7, and mild or moderate splenomegaly in 12 [23].
• Animals whose bone marrow has been infected by v-abl virus develop modest splenomegaly, marked granulocytosis, and malignant disease of several hematopoietic cell types [24].
• Free alpha globin chains were completely cleared from red blood cell membranes, splenomegaly abated, and iron deposit was almost eliminated in liver sections [25].
• Mice injected intravenously with BCR/ABL-BaF3 cells developed acute leukemia and died within 4 weeks with massive splenomegaly, elevated white blood cell counts, and anemia [26].
• Granulocytosis and splenomegaly developed in mice that received CD18-deficient fetal liver cells [27].

Gene context of Splenomegaly

• In this study we show that by 1.5 years of age, estrogen receptor beta knockout (ERbeta-/-) mice develop pronounced splenomegaly that is much more severe in females than in males [28].
• Two additional loci (Sbw1 and -2) that contributed to splenomegaly in mice suffering with systemic lupus erythematosus were also identified [29].
• Mice lacking Jak3 exhibit splenomegaly by 4 months of age [30].
• MRL-lpr/lpr mice develop lymphadenopathy and splenomegaly, and produce multiple autoantibodies, which results in autoimmune disease [31].
• FasL(-/-) mice exhibited an extreme splenomegaly and lymphadenopathy associated with lymphocytic infiltration into multiple organs and autoimmune disease [32].
• Splenomegaly induced by Leishmania major infection in mouse is controlled by Lmr3 on chromosome 5 [33] [34] Lmr5 on chromosome 10 [34], Lmr10 on chromosome 8 [33] and by Lmr14 on chromosome 2 [35]

Analytical, diagnostic and therapeutic context of Splenomegaly

• Mice infected with LP-BM5 murine leukemia virus develop lymphadenopathy, splenomegaly, hypergammaglobulinemia, and profound immunosuppression associated with enhanced susceptibility to infection [36].
• We present a young asymptomatic woman with splenomegaly and a large isolated splenic mass demonstrated by ultrasonography, 99mTc sulfur colloid, and gallium scintigraphy studies [37].
• Mice with skin tumors induced either by 7,12-dimethylbenz[a]anthracene complete carcinogenesis or subcutaneous injection of a carcinogenic keratinocyte cell line showed moderate to severe splenomegaly as a result of an increase in splenic granulocyte-macrophage and erythroid (erythroid burst-forming unit) progenitors [38].
• IFN is effective first-line therapy in patients with splenomegaly, but further work is needed to establish whether the agent should replace splenectomy in such patients [39].
• The relationships between S. haematobium, hookworm, malaria, hemoglobin level, splenomegaly, and hepatomegaly before and 8 months after treatment with a single dose of metrifonate or praziquantel were studied in Kenyan primary schoolchildren in an area where anemia, S. haematobium, and hookworm are common and malaria is holoendemic [40].

References