[Human immunodeficiency virus-associated thrombotic microangiopathies].

Human immunodeficiency virus (HIV) infection represents a risk factor for thrombotic microangiopathy. HIV-associated thrombotic microangiopathies encompass two entities with distinct pathophysiology, clinical presentation, treatment and prognosis. Thrombotic thrombocytopenic purpura associated with human immunodeficiency virus is typically characterized by a sudden onset in a patient with a moderate immune deficiency and a few events of opportunistic diseases, and a profound acquired deficiency in the von Willebrand factor cleaving protease ADAMTS13.

Current management and therapeutical perspectives in thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a particular form of thrombotic microangiopathy typically characterized by microangiopathic hemolytic anemia, profound peripheral thrombocytopenia, and a severe deficiency of the von Willebrand factor-cleaving protease ADAMTS13 (acronym for A Disintegrin And Metalloproteinase with ThromboSpondin-1 motifs [13th member of the family]). ADAMTS13 deficiency is usually severe (<10% of normal activity) and results from autoantibodies directed to ADAMTS13 (acquired TTP) or from biallelic mutations of the encoding gene. In some cases, acquired TTP occurs in association with specific conditions that must be identified for appropriate management: a HIV infection, a connective tissue disease, a pregnancy, a cancer or a treatment with antiplatelet agents.

[ADAMTS13, von Willebrand factor specific cleaving protease].

ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 repeats) is the specific von Willebrand factor (VWF)-cleaving protease. ADAMTS13 was partially purified from human plasma in 1996 and its gene was cloned in 2001. In case of vascular injury, multimeric VWF is the mediator of both platelet adhesion to the sub-endothelium and platelet aggregation within the microvessels at high shear rates of blood flow.

Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center.

Objective: To assess the efficacy and safety of rituximab in adults responding poorly to standard treatment for severe autoimmune thrombotic thrombocytopenic purpura.

Design: Open-label prospective study. Outcomes in the survivors were compared to those of 53 historical survivors who were given therapeutic plasma exchange alone or with vincristine.

Acute renal failure with lambda light chain-derived crystals in a patient with IgD myeloma.

Kidney involvement with immunoglobulin crystals usually relates to a light chain of the kappa type, in MGUS or smoldering myeloma, frequently causing Fanconi's syndrome with progressive renal insufficiency. We report on a case with severe myeloma featuring lambda light chain-derived crystals and acute kidney injury. Histology showed acute tubular necrosis and tubule obstruction with crystals, which were also abundant inside tubule epithelial cells, macrophages and bone marrow plasma cells.

Reactive haemophagocytic syndrome in 58 HIV-1-infected patients: clinical features, underlying diseases and prognosis.

Objective: To describe features of reactive haemophagocytic syndrome (RHS) in HIV-1-infected adult patients. To compare characteristics of patients with malignancy-associated RHS and infection-associated RHS.

Design And Setting: Retrospective study in three departments of Infectious Diseases/Internal Medicine at three French tertiary centres.

Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience.

Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA). In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as B-lymphocytes-depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease.

Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type.

Biopsies and cell lines of natural killer/T-cell lymphoma, nasal type (NKTCL) were subject to combined gene expression profiling and array-based comparative genomic hybridization analyses. Compared with peripheral T-cell lymphoma, not otherwise specified, NKTCL had greater transcript levels for NK-cell and cytotoxic molecules, especially granzyme H. Compared with normal NKcells, tumors were closer to activated than resting cells and overexpressed several genes related to vascular biology, Epstein-Barr Virus-induced genes, and PDGFRA.

Cancer awareness in atypical thrombotic microangiopathies.

Objective: To specify the clinical and biological characteristics of thrombotic microangiopathies (TMAs) associated with a recent diagnosis of cancer. PATIENTS AND Methods. Multicenter study involving 14 national centers.

STAT3 transcription factor is constitutively activated and is oncogenic in nasal-type NK/T-cell lymphoma.

Nasal-type natural killer (NK) cell lymphoma is an infrequent aggressive malignant disease with very poor prognosis. We aimed to explore the possible role of the transcription factor STAT3 in the pathophysiology of this malignancy, as it was involved in oncogenesis and chemoresistance. For this, we established and characterized a continuous interleukin 2-dependent NK cell line (MEC04) from a patient with a fatal nasal-type NK-cell lymphoma.

Thrombotic microangiopathies: towards a pathophysiology-based classification.

Thrombotic microangiopathies (TMA) encompass various diseases characterized by a microangiopathic hemolytic anemia, platelet clumping, and organ failure of variable severity. Thrombotic thrombocytopenic purpura (TTP) is a particularly severe form of TMA characterized by systemic organ failure which results from a severe defect in ADAMTS13, a plasma enzyme specifically involved in the cleavage of highly hemostatic unusually large (UL) von Willebrand factor (VWF) multimers into smaller and less adhesive VWF forms. Failure to degrade these UL-VWF multimers leads to excessive platelet aggregates and capillary occlusion.

BCR-ABL induces opposite phenotypes in murine ES cells according to STAT3 activation levels.

The mechanisms by which p210-BCR-ABL determines hematopoietic stem cells fate remain poorly understood. To better understand the behavior of BCR-ABL in pluripotent stem cells, we previously developed a murine embryonic stem (ES) cell model transformed by p210-BCR-ABL and reported that BCR-ABL activates STAT3, a major protein involved in ES cells self-renewal, which leads specifically to inhibition of ES cells differentiation. We show here that BCR-ABL either inhibits differentiation or, unexpectedly, induces a rapid commitment to differentiation of murine ES cells, according to the intracellular levels of activated STAT3.

Chronic lymphocytic leukemia: a hazardous condition before kidney transplantation.

Long-term survival of patients with chronic lymphocytic leukemia (CLL) is over 10 years, and such patients are thus potential kidney recipients in the case of superimposed end-stage renal disease. However, the renal and patient outcome in this condition is unknown. We report the charts of four patients with CLL who were engrafted in France with a deceased-donor kidney and underwent routine triple immunosuppressive therapy.

Human immunodeficiency virus-associated thrombotic microangiopathies: clinical characteristics and outcome according to ADAMTS13 activity.

Human immunodeficiency virus (HIV) infection is a risk factor for thrombotic microangiopathy (TMA). We sought whether a severe deficiency in ADAMTS13, the enzyme specifically involved in the cleavage of von Willebrand factor, was associated with specific presenting features and outcome in HIV-associated TMA. In this prospective, multicentre, case-control study, 29 patients of 236 in the French Network on TMA had an HIV-associated TMA.

Thrombotic thrombocytopenic purpura related to severe ADAMTS13 deficiency in children.

Thrombotic thrombocytopenic purpura (TTP) related to a severely deficient activity of the von Willebrand factor cleaving protease, ADAMTS (A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats) 13, is a life-threatening event, the onset of which may occur as early as childhood. TTP is either inherited (Upshaw-Schulman syndrome) via ADAMTS13 gene mutations (neonatal onset) or acquired via anti-ADAMTS13 autoantibodies (childhood onset). TTP is due to platelet- and von-Willebrand-factor-rich thrombi of the microvasculature, inducing mechanical hemolytic anemia, consumption thrombocytopenia, and multivisceral ischemia.

Low glycosylated ferritin, a good marker for the diagnosis of hemophagocytic syndrome.

Objective: A very low percentage of glycosylated ferritin (<20%) has only been reported in association with adult-onset Still's disease (AOSD), a disease classically associated with hemophagocytic syndrome. We undertook this study to determine whether hemophagocytic syndrome outside the context of AOSD is also associated with a very low percentage of glycosylated ferritin.

Methods: From October 2006 to September 2007, the serum level of glycosylated ferritin was determined in all consecutive patients seen in 3 departments and for whom the diagnosis of hemophagocytic syndrome was suspected.

Partial fanconi syndrome induced by imatinib therapy: a novel cause of urinary phosphate loss.

Imatinib mesylate (Gleevec, Glivec; Novartis, Basel, Switzerland) is a specific tyrosine kinase inhibitor that has become the gold-standard treatment for patients with chronic myeloid leukemia. Several tyrosine kinases inhibited by imatinib are expressed in the kidney, and although the drug is usually well tolerated, several cases of acute renal failure were reported. We describe for the first time a case of a patient treated by imatinib for chronic myeloid leukemia who developed partial Fanconi syndrome with mild renal failure, which leads to a discussion of the pathophysiological characteristics of imatinib-induced renal toxicity.

Blue-emitting iridium complexes with substituted 1,2,4-triazole ligands: synthesis, photophysics, and devices.

Neutral heteroleptic mononuclear iridium(III) complexes with (2,4-difluoro)phenylpyridine and different pyridine-1,2,4-triazole ligands were synthesized and fully characterized. We investigated the effects of substituents in the 5-position of the triazole ring on the photophysical and electrochemical behavior. Increasing the electron-withdrawing capabilities generally leads to a lowering of the HOMO level with a consequent slight widening of the HOMO-LUMO gap and a blue shift in emission.

Simultaneous regression of Philadelphia chromosome and multiple nonrecurrent clonal chromosomal abnormalities with imatinib mesylate in a patient autografted 22 years before for chronic myelogenous leukemia.

A 31-year-old patient developed chronic myelogenous leukemia (CML) in November, 1983. In November 1984, following a diagnosis of acceleration, he received an autologous hemopoietic transplant after conditioning with cyclophosphamide and total body irradiation. The autologous marrow was purged with mafosfamide.

Photochemical tuning of light emission in a conjugated polymer containing norbornadiene units in the main chain.

A conjugated alternating copolymer containing norbornadiene and bis(ethynylene)phenylene units was prepared by the Cassar-Heck-Sonogashira cross-coupling reaction. Its electroluminescence was tested in a device, and its fluorescence colour could be tuned by light-induced norbornadiene-quadricyclane isomerization.