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 clinical and pathologic findings in 24 patients with "angio-immunoblastic lymphadenopathy with dysproteinemia" (AILD) are presented. The patients' ages ranged from 44 to 80 years, with a median age of 68 years. The disease has an acute onset. In many respects, the clinical presentation is suggestive of malignant lymphoma. Generalized lymphadenopathy was always present. Hepatomegaly was found in 20 patients, splenomegaly in 17, constitutional symptoms in 20 and skin rashes in nine. Twenty patients had anemia, with positive Coombs' test in eight of 14 tested. Polyclonal hypergammaglobulinemia was found in 17 of 22 patients. Two patterns of evolution were recognizable: (1) long survival (24 to 67 months) without treatment or after the administration of intensive combination chemotherapy; and (2) rapid progression (one to 19 months) regardless of the treatment given. Sixteen patients died; postmortem examination in 10 cases showed the cause of death to be attributable to severe infection in eight patients, to renal disease in one and to cardiovascular disease in one. No evidence of malignant lymphoma was seen in any of these autopsies. Histologically, the disease is systemic, with specific lesions in the lymph nodes. The spleen, liver, bone marrow, skin and lung are also involved, but the changes are less characteristic than in the lymph nodes. In the patients in whom sequential biopsies were performed, a trend toward restoration of the nodal architecture was observed. AILD is a clinical-pathologic entity in a spectrum of yet to be defined immune reactions. The clinical, laboratory and pathologic manifestations of AILD are consistent with an autoimmune disorder, in which a deficiency of the T-cell regulatory functions probably predisposes to an abnormal proliferative and autoaggressive reaction of the B-cell system. Surgical staging procedures do not appear to be indicated. Intensive cytotoxic treatment may be hazardous in some patients, precipitating their death, but long survival after such therapy has been observed in others. Supportive therapy and small doses of steroids appear to be a safer therapeutic approach.
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PMID:Angio-immunoblastic lymphadenopathy. Diagnosis and clinical course. 119 Feb 54

Sixteen dogs with splenic infarction due to causes other than splenic torsion were identified. Dogs with splenic infarction often had multiple concurrent diseases, and surgical management of splenic infarction was associated with high mortality. Splenic infarction occurred in dogs with hypercoagulable conditions associated with liver disease, renal disease, and hyperadrenocorticism, or as a consequence of uniform splenomegaly, neoplasia, or thrombosis associated with cardiovascular disease. Clinical signs and common laboratory findings generally reflected the underlying disease process. A variety of splenic abnormalities were detected by abdominal ultrasound in 15 dogs, with the ventral extremity of the spleen being most often abnormal. Four dogs were euthanized or died because of the presence of severe systemic disease, whereas 12 dogs underwent laparotomy. Complete splenectomy was performed in 9 dogs and partial splenectomy was performed in 2 dogs. Seven dogs died in the immediate postoperative period, 3 required chronic veterinary care, and 2 had uncomplicated long-term recoveries. Splenic infaraction should be regarded as a sign of altered blood flow and coagulation, rather than as a primary disease, and surgical management should be reserved for patients with life-threatening complications such as hemoabdomen or sepsis.
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PMID:Splenic infarction in 16 dogs: a retrospective study. 767 15

Tangier disease (TD) is an autosomal recessive disorder of lipid metabolism. It is characterized by absence of plasma high-density lipoprotein (HDL) and deposition of cholesteryl esters in the reticulo-endothelial system with splenomegaly and enlargement of tonsils and lymph nodes. Although low HDL cholesterol is associated with an increased risk for coronary artery disease, this condition is not consistently found in TD pedigrees. Metabolic studies in TD patients have revealed a rapid catabolism of HDL and its precursors. In contrast to normal mononuclear phagocytes (MNP), MNP from TD individuals degrade internalized HDL in unusual lysosomes, indicating a defect in cellular lipid metabolism. HDL-mediated cholesterol efflux and intracellular lipid trafficking and turnover are abnormal in TD fibroblasts, which have a reduced in vitro growth rate. The TD locus has been mapped to chromosome 9q31. Here we present evidence that TD is caused by mutations in ABC1, encoding a member of the ATP-binding cassette (ABC) transporter family, located on chromosome 9q22-31. We have analysed five kindreds with TD and identified seven different mutations, including three that are expected to impair the function of the gene product. The identification of ABC1 as the TD locus has implications for the understanding of cellular HDL metabolism and reverse cholesterol transport, and its association with premature cardiovascular disease.
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PMID:The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease. 1043 Dec 27

Recent studies have identified the liver X receptors (LXR alpha and LXR beta) as important regulators of cholesterol metabolism and transport. LXRs control transcription of genes critical to a range of biological functions including regulation of high density lipoprotein cholesterol metabolism, hepatic cholesterol catabolism, and intestinal sterol absorption. Although LXR activity has been proposed to be critical for physiologic lipid metabolism and transport, direct evidence linking LXR signaling pathways to the pathogenesis of cardiovascular disease has yet to be established. In this study bone marrow transplantations were used to selectively eliminate macrophage LXR expression in the context of murine models of atherosclerosis. Our results demonstrate that LXRs are endogenous inhibitors of atherogenesis. Additionally, elimination of LXR activity in bone marrow-derived cells mimics many aspects of Tangier disease, a human high density lipoprotein deficiency, including aberrant regulation of cholesterol transporter expression, lipid accumulation in macrophages, splenomegaly, and increased atherosclerosis. These results identify LXRs as targets for intervention in cardiovascular disease.
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PMID:Identification of macrophage liver X receptors as inhibitors of atherosclerosis. 1219 51

Mutations in the ATP-binding cassette 1 transporter gene (ABCA1) are responsible for the genetic HDL-deficiency syndromes, which are characterized by severely diminished plasma HDL-C levels and a predisposition to cardiovascular disease and splenomegaly. The ABCA1 gene contains 50 exons and codes for a 2261-amino acid long membrane protein that facilitates phospholipid and cholesterol transport. Several mutations have been identified so far as responsible either for Tangier disease or for reduced HDL levels. We have selectively looked for additional polymorphisms in functionally relevant regions of the gene in cohorts constituted of individuals with altered HDL levels as well as healthy blood donors and octogenarians, and screened for mutations in the complete coding region of selected individuals with extremely aberrant HDL levels. In the promoter region, which is important for regulation of gene expression, we have identified several polymorphisms including one VNTR polymorphism, located at a putative ZNF202 binding site, which displayed different binding of ZNF202 in an electromobility shift assay. Three novel SNPs were discovered in the promoter region (G1047C, C1152T and C1440T). The prevalence of exchange G1047C (G-395C) was found significantly increased in probands with low HDL compared to probands with high HDL. Exchanges C1152T (C-290T) and C1440T (C-7T) were significantly more frequent in the cohort with low HDL compared to healthy blood donors and octogenarians. In the C-terminal part of ABCA1, known to interact with other proteins, two novel sequence variations (F2163S and V2244I) have been found in one phenotype related to cardiovascular disease, but none in the aforementioned cohorts. In one individual with extremely high HDL levels, the V771M polymorphism was found in a homozygous state. In patients with HDL deficiency, three novel mutations have been identified (W590L, W840R and R1068C). To facilitate further research in ABCA1 sequence variations and expand our understanding of their effects, we are introducing a webpage archive (http://www.abca1-mutants.all.at) containing all sequence variations reported in ABCA1 so far. This webpage provides a more recent and detailed summary of sequence variations and mutations in ABCA1 than existing databases and should also be of interest for molecular diagnosis of ABCA1-related HDL deficiency.
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PMID:Screening for functional sequence variations and mutations in ABCA1. 1526 83

Information about the epidemiology, clinical manifestations and comorbidities of sarcoidosis among Caucasians is relatively scarce. This review focuses primarily on the data from a recently published Caucasianpredominant population-based cohort from Olmsted County, Minnesota. Overall, the incidence rate was 10.0 per 100,000 population, which suggested that sarcoidosis is less common in Caucasians than in Blacks, but is more common in Caucasians than in Asians. Intrathoracic involvement was seen in the vast majority of patients, but less than half have respiratory symptoms. The most common extra-thoracic manifestations were skin rash followed by arthralgia, ophthalmologic involvement, hepatic involvement, splenomegaly, renal involvement, neurological involvement, extra-thoracic lymphadenopathy, exocrine gland involvement, upper respiratory tract involvement and cardiac involvement. Compared to sex and age-matched subjects, patients with sarcoidosis suffer from increased rates of cardiovascular disease, venous thromboembolism and hospitalized infection.
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PMID:Epidemiology and clinical characteristics of sarcoidosis: an update from a population-based cohort study from Olmsted County, Minnesota. 2853 17