A deletion mutant of the LMP1 oncogene of Epstein-Barr virus is associated with evolution of angioimmunoblastic lymphadenopathy into B immunoblastic lymphoma.

The latent membrane protein 1 (LMP1) oncogene is one of the major proteins synthesized by the Epstein-Barr virus (EBV). It is expressed in Reed-Sternberg cells of Hodgkin's disease (HD), tumor cells of nasopharyngeal carcinoma (NPC), and immunoblasts of angioimmunoblastic lymphadenopathy (AILD). A particular LMP1 deletion mutant was recently identified in NPC and clinically and histologically aggressive HD. We studied two patients with AILD that subsequently progressed into immunoblastic lymphoma (IBL) in order to investigate whether the LMP1 deletion mutant was implicated in progression of AILD into IBL. Immunohistology and in situ hybridization were performed on diagnostic biopsies. DNA extracted from fresh frozen material was used for rearrangement studies and polymerase chain reaction (PCR) based amplification and sequencing of portions of the LMP1 gene. Immunohistochemistry revealed B cell origin of both cases of IBL. In the first patient clonal rearrangement of the immunoglobulin heavy-chain gene was present in IBL but not in AILD. In this patient, scattered immunoblasts of AILD and numerous tumor cells of B-IBL were shown to contain EBV transcripts (EBER1) and to express LMP1. Sequence analysis of the LMP1 gene from AILD and IBL in the first, and from IBL in the second patient, revealed identical deletions and point mutations. This LMP1 deletion mutant is identical to those which have been reported in HD and NPC. Its association with evolution of AILD into B-IBL, aggressive HD and NPC, suggests that this particular mutant is more widespread than originally thought and is clinically relevant.

[Pravastatin in the treatment of primary hypercholesterolemia: a Swiss multicenter study]. / Pravastatin zur Behandlung der primären Hypercholesterinämie: Schweizer Multizenter-Studie.

Conventional lipid-lowering agents displayed only limited efficacy in lowering total and LDL cholesterol and a high incidence of side effects. Pravastatin is a new potent cholesterol-lowering agent, which selectively inhibits hepatic HMG-CoA-reductase. In a double-blind, placebo-controlled Swiss multicenter study with determination of lipids and lipoprotein in a central laboratory, the efficacy and safety of 6 months' therapy with pravastatin was evaluated in 50 patients with mild hypercholesterolemia and additional coronary risk factors. Compared to baseline and after 26 weeks' therapy, pravastatin significantly reduced total cholesterol (pravastatin vs placebo, -17% vs +7%, p < 0.0001) and LDL cholesterol (-26 vs +2%, p < 0.0001). The total/HDL cholesterol ratio ( = "atherogenic index") was comparable in the two groups at baseline (5.9 +/- 1.1 vs 6.3 +/- 0.9), and was distinctly lowered by pravastatin but not placebo (-20 vs 0%, p < 0.0001). In 11 patients in whom the reduction of serum total cholesterol after 13 weeks' treatment with 20 mg pravastatin was still below target (on average -9.1%), doubling of the dose produced a further decrease of 4.3%. Serum HDL cholesterol and serum triglyceride levels did not change significantly during pravastatin treatment as compared to baseline and placebo. Pravastatin was well tolerated during the 26 weeks without relevant subjective side-effects. There were 5 dropouts during the study, 2 patients in the pravastatin group and 3 in the placebo group. These findings document that pravastatin, administered in a single daily dose of 20 to 40 mg, effectively lowers serum cholesterol and total-/HDL-cholesterol improving action and is well tolerated.

[Anti-phospholipid antibodies as a cause of immunologic thrombopenia and thrombopathies]. / Anti-Phospholipid-Antikörper als Ursache immunologisch bedingter Thrombozytopenien und -pathien.

The simultaneous occurrence of platelet antibodies (ab) and a circulating "antithromboplastic" anticoagulant in a patient with thrombocytopenia led to the hypothesis that antiphospholipid ab may be causing both phenomena. Of 55 sera obtained from thrombocytopenic patients exhibiting a positive microtest for complement fixation (CFT) with platelets, 37 also gave positive results with highly purified phospholipids (Phl) used as antigen. In order to further evaluate the role of Phl, 40 different liposome suspensions obtained by sonication of various mixtures of Phl (with/without addition of cholesterol) were tested as antigen in the CFT with 11 selected sera, and as platelet factor 3 (PF3) reagent in the partial thromboplastin time test with normal plasma. Eight liposome preparations with PF3 activity (all containing phosphatidyl-serine) were equally active as antigen (ag) in the CFT. Liposomes composed of phosphatidyl-ethanolamine and sphingomyeline delivered ag-activity only. Since the two substances are accessible components of the outer membrane surface of thrombocytes, anti-Phl-ab may well bind to platelets in vivo, causing thrombocytopenia. Coagulation-inhibiting activity of these ab could be directly demonstrated in a PF3-test system (thrombocytopathy caused by PF3 inhibition). The identity of antithromboplastic anticoagulant and anti-Phl-ab was further substantiated by immunoabsorption, since both activities were simultaneously eliminated from the sera with a Phl-charcoal adsorbent.