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)

Scurfy (sf) is a spontaneous, sex-linked, recessive mutation that maps to the extreme proximal portion of the X chromosome, about 2 centimorgans from sparse fur (spf). Hemizygotes for sf manifest several clinical disorders, evident at 14 days of age, including scaliness and crusting of the eyelids, ears, and tail, runting, reddening and swelling of the genital papilla, anemia, cachexia, and early death (average, 24 days). Our studies indicate that the phenotype of hemizygous scurfy is not, as has been suggested, a model for human X-linked ichthyosis, but appears to be a disease primarily affecting the lymphoreticular, and possibly the hematopoietic, systems. Gross lesions include marked splenomegaly, hepatomegaly, enlarged lymph nodes, and variable thickening of the ears. The characteristic histologic lesion is a lymphohistiocytic proliferation and infiltration of peripheral lymph nodes, spleen, liver, and skin. In routine hematoxylin and eosin-stained sections, these lesions efface lymph node architecture, thicken the dermis, and form nodular portal infiltrates in the liver. Scurfy lesions characteristically contain a population of large blastlike cells with round to oval nuclei, a vesicular chromatin pattern, and prominent single nucleoli. Mixed perivascular infiltrates of lymphocytes, macrophages, and granulocytes sometimes are found in kidney, heart, pancreas, lung, and mesenteries. There is excessive hematopoiesis in the liver and spleen. Cells expressing B220 or Thy-1 antigens localize to appropriate areas in the lymph nodes and spleen, but are rare in the portal infiltrates and are absent from the skin. There is a marked, polyclonal increase in serum IgG, severe Coombs'-positive anemia, and leukocytosis with atypical mononuclear cells. Scurfy mice are negative for antinuclear antibodies. Despite their morphologically aberrant lymphoreticular system, scurfy mice can exist in a conventional environment without evidence of opportunistic infection. Raising scurfy mice in a specific-pathogen-free environment does not alter disease expression. Thus, while our findings indicate that scurfy disease may be the result of immune dysfunction, it is not a classic immunodeficiency.
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PMID:X-linked lymphoreticular disease in the scurfy (sf) mutant mouse. 205 95

Histoplasmosis naturally occurring in laboratory guinea pigs is described in its clinical, necropsy, histological and mycological aspects.The animals if adult show a chronic disease with progressive emaciation and lameness of the hind legs. The young below three months of age died in 2 to 4 weeks presenting ruffled fur, great dorsal curvature and sometimes closed eyelids and catarrhal conjunctivitis. At necropsy the principal lesions were ulcerative gastritis, hemorrhagic and catarrhal enteritis, enlarged spleen and mesenteric lymph nodes. Sometimes the liver, lungs, mediastinal lymph nodes and other organs showed lesions. Histological and mycological demonstration of the fungus completed the diagnosis and the surviving animals were burned and sanitation measures instituted. Histological evidence of histoplasmosis in a cow's lung from the area from which the grass was obtained for the feeding of the guinea pigs suggests an epidemiological link. Efforts will be made to isolate and demonstrate H. capsulatum in wild animals on the same area.
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PMID:Naturally occuring histoplasmosis in guinea pigs. 422 13

Using three murine tumor models, we compared the antitumor efficacy and certain physiological effects of an in vivo interleukin-12 (IL-12) gene therapy protocol and a systemic IL-12 protein therapy protocol. An IL-12 cDNA gene construct was administered in situ into skin tissue via gene gun delivery, and recombinant IL-12 protein was administered subcutaneously at a dose of 1 microgram/mouse/treatment. Both treatment regimes induced a comparable level of regression of established intradermal MethA sarcomas. In B16 melanoma and P815 mastocytoma models, antitumor efficacy of IL-12 protein therapy appeared to be slightly higher than that of IL-12 gene therapy; however, the protein therapy protocol in this comparative study resulted in a high level of mortality of mice. 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. Moreover, serum levels of interferon-gamma (IFN-gamma) induced in response to IL-12 gene therapy were 300-1000 times lower than those induced by the systemic IL-12 protein administration. Together, these results suggest that gene gunmediated in vivo delivery of IL-12 cDNA may be considered as a safer alternative to IL-12 protein therapy for certain human cancers.
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PMID:Gene gun-mediated IL-12 gene therapy induces antitumor effects in the absence of toxicity: a direct comparison with systemic IL-12 protein therapy. 1009 38

Photochemical treatment (PCT) with the psoralen S-59 and long wavelength ultraviolet light (UVA) inactivates high titers of contaminating viruses, bacteria, and leukocytes in human platelet concentrates. The present study evaluated the efficacy of PCT to prevent transfusion-associated graft-versus-host disease (TA-GVHD) in vivo using a well-characterized parent to F1 murine transfusion model. Recipient mice in four treatment groups were transfused with 10(8) splenic leukocytes. (1) Control group mice received syngeneic splenic leukocyte transfusions; (2) GVHD group mice received untreated allogeneic splenic leukocytes; (3) gamma radiation group mice received gamma irradiated (2,500 cGy) allogeneic splenic leukocytes; and (4) PCT group mice received allogeneic splenic leukocytes treated with 150 micromol/L S-59 and 2.1 J/cm2 UVA. Multiple biological and clinical parameters were used to monitor the development of TA-GVHD in recipient mice over a 10-week posttransfusion observation period: peripheral blood cell levels, spleen size, engraftment by donor T cells, thymic cellularity, clinical signs of TA-GVHD (weight loss, activity, posture, fur texture, skin integrity), and histologic lesions of liver, spleen, bone marrow, and skin. Mice in the control group remained healthy and free of detectable disease. Mice in the GVHD group developed clinical and histological lesions of TA-GVHD, including pancytopenia, marked splenomegaly, wasting, engraftment with donor derived T cells, and thymic hypoplasia. In contrast, mice transfused with splenic leukocytes treated with (2,500 cGy) gamma radiation or 150 micromol/L S-59 and 2.1 J/cm2 UVA remained healthy and did not develop detectable TA-GVHD. Using an in vitro T-cell proliferation assay, greater than 10(5.1) murine T cells were inactivated by PCT. Therefore, in addition to inactivating high levels of pathogenic viruses and bacteria in PC, these data indicate that PCT is an effective alternative to gamma irradiation for prevention of TA-GVHD.
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PMID:Prevention of transfusion-associated graft-versus-host disease by photochemical treatment. 1021 13

The pathogenicity of Malaysian isolates of Orientia tsutsugamushi was investigated by a mouse virulence assay. The isolates could be differentiated as low (4 isolates), moderately (3 isolates) and highly virulent (2 isolates) based on the different responses in infected mice. No direct correlation between severity of human scrub typhus infections and virulence of the O. tsutsugamushi in mice was observed. Mice infected with virulent strains of O. tsutsugamushi showed splenomegaly, ascitis accumulation and enlargement of kidneys and livers whereas avirulent O. tsutsugamushi strains were asymptomatic and exhibited ruffled fur for a short period after infection. There was low antibody response in mice infected with isolates of low pathogenicity as compared with those of highly virulent isolates. Upon dissection of the infected mice, enlargement of mouse organs such as spleen, kidney and liver was noted. Presence of rickettsemia in mice was confirmed by the growth of O. tsutsugamushi in the L929 cells when inoculated with blood from infected mice. O. tsutsugamushi was also cultured from the peritoneal exudates of the infected mice. However, DNA of O. tsutsugamushi was only detected in the peritoneal exudates (by PCR) and blood (by cell culture) and not from other tissue samples.
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PMID:Virulence of Malaysian isolates of Orientia tsutsugamushi in mice. 1269 92

In gram-negative bacteria, iron acquisition proteins are commonly regulated by Fur (ferric uptake regulator), which binds iron-regulated promoters (the Fur box). We hypothesized that Coxiella burnetii requires iron and employs an iron-regulatory system and used various approaches to define a Fur regulon. Cloned C. burnetii fur complemented an Escherichia coli fur deletion mutant. A ferrous iron transporter gene (CBU1766), a putative iron binding protein-encoding gene (CBU0970), and a cation efflux pump gene (CBU1362) were identified by genome annotation and using a Fur titration assay. Bioinformatically predicted Fur box-containing promoters were tested for transcriptional control by iron. Five genes demonstrated at least a twofold induction with minimal iron. Putatively regulated genes were evaluated in a two-plasmid regulator/promoter heterologous expression system. These data suggested a very limited Fur-regulated system in C. burnetii. In an in vitro tissue culture model, a significant increase in bacterial growth was observed with infected cells treated with deferoxamine in comparison to growth under iron-replete conditions. In an iron-overloaded animal model in vivo, the level of bacterial growth detected in the iron-injected animals was significantly decreased in comparison to growth in control animals. In a low-iron-diet animal model, a significant increase in splenomegaly was observed, but no significant change in bacterial growth was identified. The small number of predicted iron acquisition systems, few Fur-regulated genes, and enhanced replication under a decreased iron level predict a requirement of a low level of iron for survival, perhaps to avoid creation of additional reactive oxygen radicals.
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PMID:Limited role for iron regulation in Coxiella burnetii pathogenesis. 1831 81

Encapsulation of antibiotics may improve treatment of intracellular infections by prolonging antibiotic release and improving antibiotic uptake into cells. In this study, liposome-encapsulated ciprofloxacin for inhalation (CFI) was evaluated as a postexposure therapeutic for the treatment of Coxiella burnetii, the causative agent of Q fever. Intranasal treatment of male A/Jola (A/J) mice with CFI (50 mg/kg of body weight) once daily for 7 days protected mice against weight loss and clinical signs following an aerosol challenge with C. burnetii. In comparison, mice treated twice daily with oral ciprofloxacin or doxycycline (50 mg/kg) or phosphate-buffered saline (PBS) lost 15 to 20% body weight and exhibited ruffled fur, arched backs, and dehydration. Mice were culled at day 14 postchallenge. The weights and bacterial burdens of organs were determined. Mice treated with CFI exhibited reduced splenomegaly and reduced bacterial numbers in the lungs and spleen compared to mice treated with oral ciprofloxacin or doxycycline. When a single dose of CFI was administered, it provided better protection against body weight loss than 7 days of treatment with oral doxycycline, the current antibiotic of choice to treat Q fever. These data suggest that CFI has potential as a superior antibiotic to treat Q fever.
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PMID:Efficacy of liposome-encapsulated ciprofloxacin in a murine model of Q fever. 2500 5

Aleutian disease virus (ADV, Amdovirus, Parvoviridae) primarily infects farmed mustelids (mink and ferrets) but also other fur-bearing animals and humans. Three Aleutian disease (AD) cases have been described in captive striped skunks; however, little is known about the relevance of AD in free-ranging carnivores. This work describes the pathological findings and temporospatial distribution in 7 cases of AD in free-ranging striped skunks. All cases showed neurologic disease and were found in a 46-month period (2010-2013) within a localized geographical region in California. Lesions included multisystemic plasmacytic and lymphocytic inflammation (ie, interstitial nephritis, myocarditis, hepatitis, meningoencephalitis, pneumonia, and splenitis), glomerulonephritis, arteritis with or without fibrinoid necrosis in several organs (ie, kidney, heart, brain, and spleen), splenomegaly, ascites/hydrothorax, and/or encephalomalacia with cerebral microangiopathy. ADV infection was confirmed in all cases by specific polymerase chain reaction and/or in situ hybridization. The results suggest that AD is an emerging disease in free-ranging striped skunks in California.
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PMID:Aleutian Disease: An Emerging Disease in Free-Ranging Striped Skunks (Mephitis mephitis) From California. 2544 22