[Tumor metastases: mechanisms and dissemination pathways].
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Biomedical subjects
Publications and source records attributed to Y Sherer.
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The presenting symptoms of renal arteriovenous malformations are usually gross hematuria and hypertension. Herein we present an unusual case of huge renal arteriovenous malformation without these signs, but with ultrasound picture mimicking simple parapelvic cyst. Other imaging test, including Duplex ultrasound, computerized tomography and aortography, demonstrated that vascular lesion. We suggest that Duplex ultrasound should accompany the routine renal ultrasound in order not to miss such cases, especially when the physical examination suggests intra-abdominal vascular lesion or bleeding.
Magnesium, an important cofactor of more than 300 enzymes, has previously been found to modulate blood lipid levels, atherogenesis and atherosclerosis in rabbits, when added to their diet. The aim of this study was to examine whether magnesium fortification of drinking water, without a change in diet content, can affect atherogenesis. The study included six groups of LDL-receptor-deficient mice. The mice received either distilled water or water containing 50 g of magnesium sulfate per liter. In the first (12 weeks) and second (6 weeks) stages of the experiment, the mice received low- and high-cholesterol diets, respectively. At the end of each stage, blood was drawn for the determination of plasma magnesium, calcium and lipid levels. In addition, the extent of atherosclerosis was determined at the aortic sinus. In both males and females, magnesium fortification was associated with higher levels of plasma magnesium (50 and 37% increase, respectively), without any differences in plasma calcium content. The extent of atherosclerosis at the aortic sinus in the male mice that received high levels of magnesium was a third of that of the male mice that received distilled water. However, these differences were not found in the female groups. Surprisingly, the female mice that received water fortified with magnesium had higher levels of cholesterol after stage 2, whereas no differences regarding plasma lipid levels were found among the male mice. These results confirm that magnesium fortification of drinking water is capable of inhibiting atherogenesis in male LDL-receptor-deficient mice. The mechanisms of action are yet to be discovered, and are probably not related to diminished lipid excretion, but possibly to the prevention of calcium influx into vascular smooth muscle cells, elevated antioxidative capacity, or other yet undetermined mechanisms.
OBJECTIVE: Magnesium (Mg) has previously been found to modulate blood lipid levels, atherogenesis and atherosclerosis in rabbits when used as a dietary supplement. In addition, we have reported that Mg fortification of drinking water can attenuate atherogenesis in male low-density lipoprotein (LDL)-receptor-deficient mice, but had a mild and nonsignificant effect on female mice fed a high-cholesterol diet supplemented with cholic acid. The aim of this study was to examine whether Mg has an antiatherogenic effect in female mice fed a high-cholesterol diet without cholic acid. METHODS: Two groups of female LDL-receptor-deficient mice were included. The mice received either distilled water or water with 50 g of Mg sulfate per liter. In the first (12 weeks) and second (6 weeks) stages of the experiment, the mice received low- and high-cholesterol diets, respectively, both without cholic acid. At the end of each stage of the experiment, blood was drawn for the determination of plasma Mg, calcium and lipid levels. In addition, the extent of atherosclerosis was determined at the aortic sinus level. RESULTS: Mg fortification was associated with higher levels of plasma Mg while the mice were on a high-cholesterol diet, and the extent of atherosclerosis at the aortic sinus was significantly decreased in the female mice that received high levels of Mg compared with the female mice that received distilled water. The female mice that received water fortified with Mg had lower levels of triglycerides after stage 2, whereas no differences regarding cholesterol levels were found. CONCLUSION: These results confirm that Mg fortification of drinking water is capable of inhibiting atherogenesis also in female LDL-receptor-deficient mice fed a high-cholesterol diet, and demonstrate the importance of the nutritional composition of diet in this experimental model.
The pathogenesis of autoimmune disease is still an enigma. Whereas the diverse clinical manifestations of many autoimmune diseases cannot be explained by the existence of autoantibodies, idiotypic dysregulation may provide an alternative explanation. Experimental models, serum level changes of pathogenic idiotypes during exacerbation and remission, and the increased expression of pathogenic idiotypes following common infections all support this notion. In this article we review experimental models of autoimmune disease induction (systemic lupus erythematosus, antiphospholipid syndrome, Goodpasture's syndrome, autoimmune thyroiditis, and vasculitis) by manipulation of the idiotypic network, and discuss the utilization of idiotypes for the immunotherapy of autoimmune diseases and other conditions that involve the immune system (e.g., atherosclerosis).
There is a strong association between neoplasms and autoimmune diseases. Numerous autoimmune phenomena have been reported in malignancies and conversely: malignant tumors are diagnosed in increasing frequency in autoimmune conditions. We review the most common autoimmune diseases and autoantibodies found in malignancies, discuss the therapeutic role of these autoantibodies in cancer, and summarize the current knowledge on malignant transformation in autoimmunity.
Although some autoimmune diseases are known to be associated with a higher incidence of cancers, they are not usually considered as paraneoplastic diseases, but rather as autoimmune diseases that may be neoplasia-associated, since currently it is not known whether the tumor leads to their development, or alternatively another underlying condition turns the patients prone to both cancer and autoimmunity. We review the association of cancer with pemphigus, paraneoplastic pemphigus, myasthenia gravis and Eaton-Lambert syndrome, and discuss the importance of looking for an occult malignancy in a patient with a newly-diagnosed autoimmune disease that is known to be associated with cancer.
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OBJECTIVE: As the antiphospholipid syndrome (APS) is characterized by antibodies which bind negatively charged phospholipids either directly or mainly through different target epitopes located on the beta-2-glycoprotein-I (beta 2GPI) molecule, the aim of this study is to describe an additional target epitope for anti-cardiolipin binding. METHODS: The binding characteristics of affinity purified anti-cardiolipin antibodies from a patient with monoclonal gammopathy associated with clinically overt APS were studied; inhibition studies were also carried out. These antibodies were used for the active induction of experimental APS. RESULTS: The affinity purified anti-cardiolipin antibodies were found to bind a target epitope created by the complex of cardiolipin/beta 2GPI, while not reacting with a complex composed by another phospholipid (phosphatidylserine/beta 2GPI), as confirmed by direct binding and competition assays. Immunization of naive mice with this unique affinity purified anti-cardiolipin antibody resulted in the induction of experimental APS (thrombocytopenia, prolonged coagulation timed and fetal resorptions). The anti-cardiolipin/beta 2GPI injected mice developed high titers of mouse anti-cardiolipin/beta 2GPI antibodies with the same binding characteristics as the human antibody which was used for disease induction. CONCLUSION: APS is a unique syndrome that is characterized by a diversity of pathogenic anti-phospholipid antibodies which may explain the diversity of clinical manifestations reported in patients.
OBJECTIVE: The SA1 and 16/6 idiotypes can be found in some patients with systemic lupus erythematosus (SLE) or anti-phospholipid syndrome (APS). The aim of this study was to ascertain the prevalence of these idiotypes in a large cohort of SLE patients, and to determine whether their presence is correlated with the anticardiolipin (aCL) and anti-dsDNA antibodies or with the clinical manifestations of SLE. METHODS: 492 SLE patients were evaluated for clinical manifestations of SLE and were assigned a disease severity score. ds-DNA autoantibodies, aCL autoantibodies of the IgM, IgG and IgA isotypes, and SA1 and 16/6 idiotypes were also determined in these patients. RESULTS: The prevalence of the SA1 and 16/6 idiotypes in the 492 SLE patients was found to be 11% and 5.1%, respectively, and these idiotypes were significantly more prevalent in the patients who had aCL antibodies of either the IgG, IgM or IgA isotypes. Moreover, while the 16/6 idiotype was not associated with the clinical manifestation of either SLE or APS, the SA1 idiotype was found significantly more frequently in patients who had vascular events Raynaud's phenomenon or hemolytic anemia (p = 0.016, 0.01, 0.01, respectively). CONCLUSION: SLE patients with the SA1 idiotype may run a higher risk of developing vascular events, Raynaud's phenomenon or hemolytic anemia. These clinical manifestations can be attributed to both SLE and secondary APS when aCL autoantibodies are also found. These results indicate that the possible pathogenicity of certain idiotypes in SLE cannot be excluded.