A severe case of neuroleukemiosis caused by B cell chronic lymphocytic leukemia, presenting as mononeuritis multiplex.

Aims: To report an exceptional case of nerve infiltration by an otherwise benign chronic B cell leukemia, inducing severe mononeuritis multiplex.

Methods: The patient underwent extensive evaluation, including nerve conduction study and myography, brain and plexus MRI, and nerve biopsy.

Results: The clinical and electrophysiological diagnosis was a mononeuritis multiplex with severe motor and sensory involvement; only the nerve biopsy allowed definite diagnosis and introduction of chemotherapy, leading to resolution of sensory deficit and progressive motor improvement.

Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis: Review of Published Cases.

Desmoid-type fibromatosis (DTF) is a very rare variant of papillary thyroid carcinoma (PTC). It is essentially a dual tumor with a component of classical PTC with malignant epithelial proliferation (-mutated) and another component of mesenchymal proliferation (-mutated). We conducted a literature review on PTC-DTF.

ABCG2 Is Overexpressed on Red Blood Cells in Ph-Negative Myeloproliferative Neoplasms and Potentiates Ruxolitinib-Induced Apoptosis.

Myeloproliferative neoplasms (MPNs) are a group of disorders characterized by clonal expansion of abnormal hematopoietic stem cells leading to hyperproliferation of one or more myeloid lineages. The main complications in MPNs are high risk of thrombosis and progression to myelofibrosis and leukemia. MPN patients with high risk scores are treated by hydroxyurea (HU), interferon-α, or ruxolitinib, a tyrosine kinase inhibitor.

Fetal hemoglobin rescues ineffective erythropoiesis in sickle cell disease.

While ineffective erythropoiesis has long been recognized as a key contributor to anemia in thalassemia, its role in anemia of sickle cell disease (SCD) has not been critically explored. Using in vitro and in vivo derived human erythroblasts we assessed the extent of ineffective erythropoiesis in SCD. Modeling the bone marrow hypoxic environment, we found that hypoxia induces death of sickle erythroblasts starting at the polychromatic stage, positively selecting cells with high levels of fetal hemoglobin (HbF).

Oxidative stress activates red cell adhesion to laminin in sickle cell disease.

Vaso-occlusive crises are the hallmark of sickle cell disease (SCD). They are believed to occur in two steps, starting with adhesion of deformable low-dense red blood cells (RBCs), or other blood cells such as neutrophils, to the wall of post-capillary venules, followed by trapping of the denser RBCs or leukocytes in the areas of adhesion because of reduced effective lumen-diameter. In SCD, RBCs are heterogeneous in terms of density, shape, deformability and surface proteins, which accounts for the differences observed in their adhesion and resistance to shear stress.

Dimerization and phosphorylation of Lutheran/basal cell adhesion molecule are critical for its function in cell migration on laminin.

Tumor cell migration depends on the interactions of adhesion proteins with the extracellular matrix. Lutheran/basal cell adhesion molecule (Lu/BCAM) promotes tumor cell migration by binding to laminin α5 chain, a subunit of laminins 511 and 521. Lu/BCAM is a type I transmembrane protein with a cytoplasmic domain of 59 (Lu) or 19 (Lu(v13)) amino acids.

Insights into determinants of spleen injury in sickle cell anemia.

Spleen dysfunction is central to morbidity and mortality in children with sickle cell anemia (SCA). The initiation and determinants of spleen injury, including acute splenic sequestration (ASS) have not been established. We investigated splenic function longitudinally in a cohort of 57 infants with SCA enrolled at 3 to 6 months of age and followed up to 24 months of age and explored the respective contribution of decreased red blood cell (RBC) deformability and increased RBC adhesion on splenic injury, including ASS.

Absolute proteome quantification of highly purified populations of circulating reticulocytes and mature erythrocytes.

Reticulocytes produced in the bone marrow undergo maturation in the bloodstream to give rise to erythrocytes. Although the proteome of circulating red cells has been the subject of several reports, the cellular populations used for these studies were never completely devoid of reticulocytes. In our current study, we used highly purified erythrocyte and reticulocyte populations to quantify the absolute expression levels of the proteins in each cell population.

Impact of hydroxycarbamide and interferon-α on red cell adhesion and membrane protein expression in polycythemia vera.

Polycythemia vera is a chronic myeloproliferative neoplasm characterized by the JAK2V617F mutation, elevated blood cell counts and a high risk of thrombosis. Although the red cell lineage is primarily affected by JAK2V617F, the impact of mutated JAK2 on circulating red blood cells is poorly documented. Recently, we showed that in polycythemia vera, erythrocytes had abnormal expression of several proteins including Lu/BCAM adhesion molecule and proteins from the endoplasmic reticulum, mainly calreticulin and calnexin.

High Affinity Binding of Escherichia coli Cytotoxic Necrotizing Factor 1 (CNF1) to Lu/BCAM Adhesion Glycoprotein.

The protein toxin Cytotoxic Necrotizing Factor 1 (CNF1) is a major virulence factor of pathogenic strains. It belongs to a family of single chain AB-toxins, which enter mammalian cells by receptor-mediated endocytosis. Recently, we identified the Lutheran (Lu) adhesion glycoprotein/basal cell adhesion molecule (BCAM) as a cellular receptor for CNF1.

Staphylococcus aureus Targets the Duffy Antigen Receptor for Chemokines (DARC) to Lyse Erythrocytes.

In order for Staphylococcus aureus to thrive inside the mammalian host, the bacterium has to overcome iron scarcity. S. aureus is thought to produce toxins that lyse erythrocytes, releasing hemoglobin, the most abundant iron source in mammals.

Studies of a murine monoclonal antibody directed against DARC: reappraisal of its specificity.

Duffy Antigen Receptor for Chemokines (DARC) plays multiple roles in human health as a blood group antigen, a receptor for chemokines and the only known receptor for Plasmodium vivax merozoites. It is the target of the murine anti-Fy6 monoclonal antibody 2C3 which binds to the first extracellular domain (ECD1), but exact nature of the recognized epitope was a subject of contradictory reports. Here, using a set of complex experiments which include expression of DARC with amino acid substitutions within the Fy6 epitope in E.

Hydroxycarbamide decreases sickle reticulocyte adhesion to resting endothelium by inhibiting endothelial lutheran/basal cell adhesion molecule (Lu/BCAM) through phosphodiesterase 4A activation.

Vaso-occlusive crises are the main acute complication in sickle cell disease. They are initiated by abnormal adhesion of circulating blood cells to vascular endothelium of the microcirculation. Several interactions involving an intricate network of adhesion molecules have been described between sickle red blood cells and the endothelial vascular wall.

Including patients in resuscitation decisions in Switzerland: from doing more to doing better.

Background: Decisions regarding Cardio-Pulmonary Resuscitation (CPR) and Do Not Attempt Resuscitation (DNAR) orders remain demanding, as does including patients in the process.

Objectives: To explore physicians' justification for CPR/DNAR orders and decisions regarding patient inclusion, as well as their reports of how they initiated discussions with patients.

Methods: We administered a face-to-face survey to residents in charge of 206 patients including DNAR and CPR orders, with or without patient inclusion.

[Management of anal canal carcinoma].

Although anal canal squamous cell carcinoma is rare, the general practitioner should consider this diagnosis in a patient with persistent lower abdominal symptoms. While classically observed in older women, an increased incidence is also seen in HIV-positive patients or patients with a history of human papillomavirus infection. Initial diagnosis and local work-up require assessment by a proctologist.

Successful closure of anal cancer-related fistulas with upfront intra-arterial chemotherapy: a report of 8 cases.

Background: Fistulas arising from the perforation of anal cancer into adjacent organs are a debilitating complication in the course of the disease.

Objective: We studied intra-arterial chemotherapy as a strategy to close such fistulas before the initiation of standard chemoradiation.

Design: This study was based on a retrospective chart review.

'Do not attempt resuscitation' and 'cardiopulmonary resuscitation' in an inpatient setting: factors influencing physicians' decisions in Switzerland.

Objective: To determine the prevalence of cardiopulmonary resuscitation (CPR) and do-not-attempt-resuscitation (DNAR) orders, to define factors associated with CPR/DNAR orders and to explore how physicians make and document these decisions.

Methods: We prospectively reviewed CPR/DNAR forms of 1,446 patients admitted to the General Internal Medicine Department of the Geneva University Hospitals, a tertiary-care teaching hospital in Switzerland. We additionally administered a face-to-face survey to residents in charge of 206 patients including DNAR and CPR orders, with or without patient inclusion.

[Ovarian cancer screening: recommendations for clinical pratice].

Ovarian cancer accounts for a minority of female cancers but remains the leading cause of death from gynaecologic cancers and the fifth leading cause of all cancer-related deaths among women. More than two thirds of cases of ovarian cancer are diagnosed once the disease becomes symptomatic, i.e.

A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines.

Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells.

Functional reconstitution into liposomes of purified human RhCG ammonia channel.

Background: Rh glycoproteins (RhAG, RhBG, RhCG) are members of the Amt/Mep/Rh family which facilitate movement of ammonium across plasma membranes. Changes in ammonium transport activity following expression of Rh glycoproteins have been described in different heterologous systems such as yeasts, oocytes and eukaryotic cell lines. However, in these complex systems, a potential contribution of endogenous proteins to this function cannot be excluded.

[Surveillance following curative therapy for breast cancer].

Surveillance following curative therapy for localised breast cancer has two major aims: 1) diagnosis of recurrence or a second tumor: regular interviews and physical examinations with a frequency adapted to each case, and yearly mammography (+/- ultrasonography), are the only recommended procedure. Additional screening is not indicated in asymptomatic patient. 2) Screening for complications and side effects due to treatment: tamoxifen treatment should be stopped one week prior to any surgery or long trip to avoid thromboembolic events, and any metrorrhagia should be investigated due to the risk for endometrial cancer.

New procedures for glycophorin A purification with high yield and high purity.

Glycophorin A (GPA) is the major glycoprotein of the human erythrocyte membrane. It is known to form, in SDS gels as well as in a membrane environment, homodimers, and also heterodimers with the homologous molecule Glycophorin B (GPB). It is shown in this report that the propensity of GPA to dimerize with GPB precludes satisfactory preparation with high yield of pure GPA using classical techniques including SEC and RPLC.

A murine monoclonal antibody against Kx protein which reacts also with beta-spectrin.

Kx is a polytopic membrane protein of human erythrocytes carrying the Kx blood group antigen, which is deficient in rare patients with McLeod syndrome. Kx is disulphide bond linked to the Kell glycoprotein, which is a bitopic type II membrane protein carrying the Kell blood group antigen. Mice immunized with a synthetic peptide predicted to be located on the second external loop of Kx produced a monoclonal antibody called 3E12 which does not recognize red cells with common Kell phenotype by agglutination and flow cytometry.