Impact of Folinic Acid Dosing on Efficacy and Toxicity of High-Dose Methotrexate in Central Nervous System Lymphoma.

Introduction: High-dose methotrexate (HDMTX)-based regimens are the treatment of choice in primary central nervous system lymphoma (PCNSL). Folinic acid (FA) rescue is used to mitigate the toxic effects of MTX on normal cells. However, the optimal dosing of FA in PCNSL remains uncertain.

Peripheral Blood Cell Mitochondrial Dysfunction in Myelodysplastic Syndrome Can Be Improved by a Combination of Coenzyme Q10 and Carnitine.

Structural mitochondrial abnormalities and genetic aberrations in mitochondrial proteins have been known in Myelodysplastic syndrome (MDS), yet there is currently little data regarding MDS's metabolic properties and energy production cells. In the current study, we used state-of-the-art methods to assess OXPHOS in peripheral blood cells obtained from MDS patients and healthy controls. We then assessed the effect of food supplements-Coenzyme Q10 and carnitine on mitochondrial function and hematological response.

[THE ROLE OF THE PLANT ARTEMISIA IN SURVIVAL AND INDUCTION OF APOPTOSIS OF B CELLS IN CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)].

Background: The cytotoxic effect of plants such as green tea and turmeric (curcumin) on B chronic lymphocytic leukemia (CLL) cells has been established. The plant Artemisia has been used in China for anti-cancer and anti-malaria applications. In Israel, Artemisia absinthium ("the Chiba") is used to release abdominal pain.

Loss of Muscle MTCH2 Increases Whole-Body Energy Utilization and Protects from Diet-Induced Obesity.

Mitochondrial carrier homolog 2 (MTCH2) is a repressor of mitochondrial oxidative phosphorylation (OXPHOS), and its locus is associated with increased BMI in humans. Here, we demonstrate that mice deficient in muscle MTCH2 are protected from diet-induced obesity and hyperinsulinemia and that they demonstrate increased energy expenditure. Deletion of muscle MTCH2 also increases mitochondrial OXPHOS and mass, triggers conversion from glycolytic to oxidative fibers, increases capacity for endurance exercise, and increases heart function.

Balancing glycolysis and mitochondrial OXPHOS: lessons from the hematopoietic system and exercising muscles.

Living organisms require a constant supply of safe and efficient energy to maintain homeostasis and to allow locomotion of single cells, tissues and the entire organism. The source of energy can be glycolysis, a simple series of enzymatic reactions in the cytosol, or a much more complex process in the mitochondria, oxidative phosphorylation (OXPHOS). In this review we will examine how does the organism balance its source of energy in two seemingly distinct and unrelated processes: hematopoiesis and exercise.

Can a rare form of myasthenia gravis shed additional light on disease mechanisms?

A healthy 43-year-old physician developed gradually progressive and fluctuating fatigable muscle weakness involving ocular, limb, bulbar and respiratory muscles, with episodic acute respiratory failure, eventually necessitating intermittent non-invasive respiratory support (NIV). A mild short episode occurred 15 years earlier with complete resolution. Electromyography (EMG) studies and acetylcholine receptor (AchR) antibodies were repeatedly non-diagnostic.

Benefits versus risks of pharmacological prophylaxis to prevent symptomatic venous thromboembolism in unselected medical patients revisited. Meta-analysis of the medical literature.

A significant proportion of the outcomes reported in trials assessing venous thromboembolism (VTE) prophylaxis in medical patients are related to asymptomatic events found on routine imaging studies. The implications of these events are controversial. Moreover, such trials did not always reflect the patient mix in today's internal medicine departments.

Venous thromboembolism prophylaxis of acutely ill hospitalized medical patients. Are we over-treating our patients?

Venous thromboembolism (VTE) is prevalent and is associated with dire consequences. Many VTE events are related to medical hospitalization, and some of these events are avoidable when appropriate measures are taken. Despite the current knowledge of the prevalence and burden of this disease, many internists are reluctant to prescribe pharmacological prophylaxis to "at-risk" medical inpatients.

The cytokine midkine and its receptor RPTPζ regulate B cell survival in a pathway induced by CD74.

Lasting B cell persistence depends on survival signals that are transduced by cell surface receptors. In this study, we describe a novel biological mechanism essential for survival and homeostasis of normal peripheral mature B cells and chronic lymphocytic leukemia cells, regulated by the heparin-binding cytokine, midkine (MK), and its proteoglycan receptor, the receptor-type tyrosine phosphatase ζ (RPTPζ). We demonstrate that MK initiates a signaling cascade leading to B cell survival by binding to RPTPζ.

Attitudes towards and practice of venous thromboembolism prevention in general internal medicine wards: a multinational survey from member countries of the European Federation of Internal Medicine.

Introduction: Hospitalised patients in Internal Medicine departments are at risk of venous thromboembolism (VTE). Adherence to risk stratification methods is poor. We conducted a survey among Internists from member countries of the European Federation of Internal Medicine (EFIM) to assess current knowledge and attitude towards VTE prevention.

On the clinical encounter with 'zebras' - the science and art of rare diseases.

Taught since medical school to concentrate on the more common disease entities, physicians may become insensitive to the possibility of encountering a rare disease ("zebra") or even an unusual presentation of one. The personal experience of one of the authors prompted this article, presenting an alternative view. We stress the need to carefully consider at times even rare diagnostic entities and their potentially unusual presentations.

The secret second life of an innocent chaperone: the story of CD74 and B cell/chronic lymphocytic leukemia cell survival.

This review deals with the cytokine macrophage migration inhibitory factor (MIF) and its receptor, CD74. MIF and CD74 have been shown to regulate peripheral B cell survival and were associated with tumor progression and metastasis. CD74 expression has been suggested to serve as a prognostic factor in many cancers, with higher relative expression of CD74 behaving as a marker of tumor progression.

TAp63 regulates VLA-4 expression and chronic lymphocytic leukemia cell migration to the bone marrow in a CD74-dependent manner.

The hallmark of chronic lymphocytic leukemia (CLL) is the relentless accumulation of mature lymphocytes, mostly due to their decreased apoptosis. CD74 was recently shown to serve as a survival receptor on CLL cells. In this study, we show that stimulation of CD74 with its natural ligand, migration inhibitory factor, initiates a signaling cascade that results in upregulation of TAp63, which directly regulates CLL survival.

Circulating B-cell chronic lymphocytic leukemia cells display impaired migration to lymph nodes and bone marrow.

Homing to secondary lymphoid organs and bone marrow (BM) is a central aspect of leukemic pathophysiology. We investigated the roles of the two major lymphocyte integrins LFA-1 and VLA-4 on B-cell chronic lymphocytic leukemia (CLL) cells in these processes. We found that the majority of CLL cells expressed significantly reduced LFA-1 due to low beta2 integrin transcripts.

Unbalanced protein S deficiency due to warfarin treatment as a possible cause for thrombosis.

The prothrombin time/International Normalized Ratio is an accurate parameter for following most warfarin-treated patients. However, it reflects mostly factor VII levels, and significant disproportionate alterations in other vitamin K-dependent factors may not be reflected properly. We report a rare case of a woman who developed arterial thrombosis whilst receiving therapeutic doses of warfarin, and was found to have a significant and unbalanced protein S deficiency.

IL-8 secreted in a macrophage migration-inhibitory factor- and CD74-dependent manner regulates B cell chronic lymphocytic leukemia survival.

Chronic lymphocytic leukemia (CLL) is a malignant disease of small mature lymphocytes. Previous studies have shown that CLL B lymphocytes express relatively large amounts of CD74 mRNA relative to normal B cells. In the present study, we analyzed the molecular mechanism regulated by CD74 in B-CLL cells.