Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonalcohol-induced fatty liver is widely believed to be a benign condition with little or no risk of disease progression. There have been occasional reports of progression to cirrhosis but none in the absence of preexisting fibrosis on the index biopsy specimen even when co-existing hepatitis was present (steatohepatitis). From our histological database (1978 to 1985), we identified 161 patients with fatty liver seen at our institution and traced the case notes of 156. One hundred five patients were initially excluded as having an alcohol-induced cause, and the remaining 51 either were seen in the clinic (37) or had died, in which cases copies of their death certificates were obtained (14). A further 7 patients were excluded after clinic attendance gave evidence of alcohol excess and another 4 after review of their initial biopsy showed the presence of fibrosis or steatohepatitis. The apparent cause of the steatosis in the 40 included patients with strictly nonalcohol-induced pure fatty liver was obesity in 12, diabetes in 4 (1 obese patient), and cachexia associated with extrahepatic malignancy in 6. Four of the remaining 19 had serological evidence of an autoimmune disorder, but none of these had any clinical or histological features of autoimmune liver disease. Nine patients had evidence of hyperlipidemia, 3 of whom were also obese. At a median follow-up of 11 years (7 to 16), 12 of 26 living patients had abnormal results of liver blood tests and had repeat liver biopsies performed. None had progressed to steatohepatitis or cirrhosis; 1 obese patient had developed mild fibrosis 9.8 years after her index biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The natural history of nonalcoholic fatty liver: a follow-up study. 748 79

MRL/lpr mice develop severe autoimmune disease and vasculitis by 5 months of age, whereas congenic strain MRL/n mice exhibit much milder vasculitis with a later age of onset. When maintained on a high-fat, high-cholesterol (atherogenic) diet, strain MRL/lpr mice exhibited a striking deposition of lipid in both the large and small coronary arteries, whereas strain MRL/n mice exhibited very little lipid accumulation. Neither strain exhibited lipid accumulation on a low-fat chow diet. The atherogenic diet induced hyperlipidemia in both strains, but surprisingly the levels of atherogenic apolipoprotein B-containing lipoproteins were much lower in MRL/lpr mice. Immunohistochemical studies revealed that immune complexes (immunoglobulins G and M), T and B lymphocytes, macrophages, granulocytes, apolipoprotein B, and serum amyloid A proteins were present in the walls of the coronary arteries that had vasculitis and lipid accumulation. By 6-7 months of age, MRL/lpr mice had a higher incidence of myocardial infarction in the atherogenic diet group (53%) compared with the chow group (14%), whereas MRL/n mice exhibited no myocardial infarction on either diet. These results suggest important interactions between vasculitis, hyperlipidemia, and arterial lipid accumulation. They support the concept that injury to the vessel wall in immune-complex-mediated vasculitis increases lipid deposition in the presence of hyperlipidemia.
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PMID:Immune-complex-mediated vasculitis increases coronary artery lipid accumulation in autoimmune-prone MRL mice. 849 14

Only a few cases of type I hyperlipidemia occurring in patients with autoimmune disease have been reported. We describe the case of a 35-yr-old woman suffering from severe type I hyperchylomicronemia. A combination of various hypolipidemic treatments, including strict hypolipidemic dietary therapy and administration of fibrates or n-3 fatty acids, was inefficient. Because of a history of familial autoimmunity, we introduced an immunosuppressive therapy that resulted in consistent long term and stable remission. Two attempts to reduce the immunosuppressor dose resulted in major relapses. To explain the defect of chylomicron hydrolysis, we investigated the postheparin plasma lipase activities. Hepatic triglyceride lipase activity was normal, whereas that of lipoprotein lipase (LPL) was reduced to about 30% of normal. Immunosuppressive therapy resulted in a complete and durable normalization of LPL activity. Using Western blot analysis, we found in the plasma of the patient a circulating IgG specifically directed against LPL, which became undetectable during immunosuppressive therapy. Western blot analysis revealed that the whole circulating anti-LPL autoantibody was bound to chylomicrons. Proteins extracted from patient's chylomicrons were able to induce a dose-related inhibition of LPL activity in vitro, whereas that of hepatic triglyceride lipase remained unchanged. These data constitute the first description of autoimmune hyperchylomicronemia due to an exclusive defect of LPL activity, and they show that a complete remission has been obtained after immunosuppressive therapy. Finally, our finding that the anti-LPL autoantibody is bound to chylomicrons emphasizes their previously unrecognized ability to transport LPL, already described for other lipoprotein fractions.
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PMID:Characterization of a new case of autoimmune type I hyperlipidemia: long-term remission under immunosuppressive therapy. 906 84

Turner's syndrome is characterized, amongst other things, by growth retardation with high serum levels of insulin-like growth factor 1 (IGF-I) in relation to growth, by a tendency to autoimmune disease and by insulin resistance with hyperlipidaemia. Assuming a role for IGF-I subresponsiveness in the last two features, the present study was designed to evaluate in patients with Turner's syndrome their monocyte/macrophage response to growth hormone (GH) and to IGF-I with respect to low-density lipoprotein (LDL) degradation and to the monocyte-dependent lymphocyte proliferation. Nineteen patients with Turner's syndrome and puberty-matched control subjects were studied. Monocytes were isolated from the blood of the patients and the control group, and cultured to develop into macrophages. The cells were then incubated with 125I-labelled LDL (25 micrograms of protein mL-1) in the absence or presence of 50 ng mL-1 IGF-I or GH, and cellular lipoprotein degradation was determined. GH and IGF-I effects on T-cell proliferation were measured in autologous mixed lymphocyte reaction Monocytes/macrophages degradation of LDL was lower in Turner's syndrome patients than in control subjects (P < 0.05). IGF-I stimulated LDL degradation by 42 +/- 8% in the control subjects and by only 16 +/- 7% in Turner's syndrome patients (P < 0.05). Control lymphocyte proliferation in AMLR was significantly augmented by 50-100 ng mL-1 GH or IGF-I. Lymphocytes derived from peripheral blood of Turner's syndrome patients remained almost unaffected by either GH or IGF-I. Measurement of IL-2 secretion by purified blastoid T lymphocytes-I. revealed a significant augmentation by 100 ng mL-1 GH and by 50-100 ng mL-1 IGF-I in control subjects, and almost no response in Turner's0 ng syndrome. Turner's syndrome is associated with decreased sensitivity of peripheral blood mononuclear cells to GH and to IGF-I, as is evident by the reduction in LDL degradation, monocyte-stimulated T-lymphocyte proliferation and IL-2 secretion by blastoid T cells.
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PMID:Decreased sensitivity to insulin-like growth factor I in Turner's syndrome: a study of monocytes and T lymphocytes. 926 39

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder affecting multiple organ systems. Treatment of the disease has contributed dramatically in the long-term survival of the patients and now SLE has become a chronic inflammatory disorder. Present data suggest 5, 10 and 20-year survival rates of 93%, 85% and 68% respectively. Accelerated atherosclerosis and early coronary artery disease have become important causes of death and hospitalisation in SLE patients. Many cardiovascular risk factors can be considered: disease activity (particularly kidney involvement), sedentary life (in nearly 70% of the patients), hyperlipidemia, antiphospholipid antibodies, serum homocysteine and many others. Although traditional risk factors are operative in patients with SLE, the risk for myocardial infarction was increased 8.3 folds after controlling these factors in a study, suggesting that SLE itself was the strongest risk factor for cardiovascular disease. Lipid abnormalities may play a major role in increasing cardiovascular risk in SLE patients who are characterized by elevated triglycerides, very low-density lipoprotein cholesterol (VLDL-C), reduced levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo) A-1. Anticardioli-pin antibodies may influence lipid levels in SLE; in particular SLE patients with IgG anticardiolipin antibodies had significantly lower HDL-C compared with patients with no anticardiolipin antibodies. Elevation of serum homocysteine is observed in 15% of SLE patients and is significantly associated with the development of stroke and arterial thrombotic events. The antiphospholipid syndrome (APS) is an acquired thrombotic disorder characterised by recurrent venous or arterial thrombosis or recurrent miscarriages, or both, associated with the presence in the serum of IgG or IgM anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LAC). APS may occur as a primary disorder (PAPS) or associated with connective tissue diseases, mainly systemic lupus erythematosus (secondary APS). Primary and secondary APS are both associated with a significant increase of cardiovascular risk.
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PMID:[Cardiovascular risk factors in systemic lupus erythematosus and in antiphospholipid syndrome]. 1285 54

Atherosclerosis may be considered an inflammatory disease characterised by the development of atherosclerotic plaques and ischaemic cardiovascular events. Increased prevalence of cardiovascular morbidity and mortality due to (premature) atherosclerosis has been observed in patients with autoimmune diseases like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Wegener's granolumatosis. This increased prevalence cannot be explained by the presence of the traditional cardiovascular risk factors such as hypertension, hyperlipidaemia, diabetes mellitus and smoking. Therefore, other risk factors must be present in patients with systemic autoimmune disease. Although the mechanisms have not been fully unravelled, endothelial cell (EC) activation through autoantibodies seems to be one of the factors involved. EC activation results in EC dysfunction. It is supposed that chronic EC dysfunction, as present in patients with systemic autoimmune disorders, contributes to the development of premature atherosclerosis and results in an increased prevalence of cardiovascular disease.
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PMID:Endothelial activation, endothelial dysfunction and premature atherosclerosis in systemic autoimmune diseases. 1469 39

Severe hypertriglyceridaemia is a rare presentation usually associated with acute pancreatitis. We present two case reports of severe hypertriglyceridaemia occurring in patients with previous autoimmune disease and haematological and solid malignancies but no evidence of prior or concurrent pancreatitis or hyperlipidaemia. These case reports illustrate that haematological and solid organ malignancies and autoimmunity may be relevant as exacerbating factors in the presentation of severe type IV or V hypertriglyceridaemia.
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PMID:Hypertriglyceridaemia and malignancy. 1585 4

Corticosteroids have always played a valuable role in transplantation. Unfortunately, they are subject to a wide range of side effects, such as hyperlipidemia, hypertension, diabetes mellitus, osteoporosis, growth retardation and Cushingoid appearance. Steroids may also exacerbate problems that existed before surgery, including malignancy, hepatitis B and hepatitis C. New, powerful immunosuppressants have allowed steroid use to be reduced or avoided altogether, but use of these regimens is not simple and may be associated with late acute rejection and recurrence of autoimmune disease. The present review examines the rationale for steroid avoidance in liver transplantation and assesses the new regimens that are currently being developed.
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PMID:Steroid avoidance in liver transplantation. 1680 21

Alopecia areata is an organ specific autoimmune disease in which hair is lost in various patterns. Its most extreme form, alopecia universalis, is the total loss of all scalp and body hair. This form of the condition is very resistant to treatment and spontaneous remission is quite rare. The following is a case of a 54-year-old male with longstanding alopecia universalis who began to grow dense hair on his scalp as well as patchy hair growth on his face, pubic and axillary areas one month after starting a course of simvastatin 40 mg and ezetimibe 10 mg daily prescribed for his hyperlipidemia. For 2 years prior to starting the combination drug, he had taken simvastatin 40 mg alone without evidence of any hair growth. The combination of simvastatin and ezetimibe has previously demonstrated synergistic immunomodulatory effects, which most likely accounts for the clinical response in this case.
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PMID:Case reports: alopecia universalis: hair growth following initiation of simvastatin and ezetimibe therapy. 1794 69

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factor belonging to a nuclear hormone receptor superfamily, containing three isoforms (alpha, beta/delta, and gamma). PPARs play a critical physiological role as a primary lipid sensor and regulator of lipid metabolism. Thus, its ligands are clinically used for treatment of type 2 diabetes and hyperlipidemia. On the other hand, PPAR ligands exert the antineuroinflammatory activity through preventing upregulation of inflammatory mediators in animal models for neurodegenerative disease and autoimmune disease. Neuropathic pain and inflammatory pain, clinically important one, are chronically progressed and underlain by neuroinflammation. In a few years, some studies using experimental models emerge that administration of PPAR ligands reduces inflammatory pain and neuropathic pain. PPAR ligands repress expression of genes for inflammatory mediators involved in both pains, such as proinflammatory cytokines, by a molecular mechanism termed ligand-dependent direct transrepression. Alternative mechanism is independent of transcriptional regulation of target genes, such as inhibition of activity of ion channels involved in the development of inflammatory pain and neuropathic pain, and therefore the analgesic effect occurs with rapid onset. The effects of PPAR ligands on neuroinflammation in animal models suggest their possible use for treating human inflammatory pain and neuropathic pain.
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PMID:PPAR and Pain. 1960 69


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