IL-5 receptor α levels in patients with marked eosinophilia or mastocytosis.

Background: IL-5 plays a central role in the development and maintenance of eosinophilia (EO) and eosinophil activation in a wide variety of eosinophilic disorders. Although IL-5, IL-3, and GM-CSF can modulate the expression of IL-5 receptor α (IL-5Rα) on eosinophils in vitro, little is known about soluble and surface IL-5Rα levels in vivo.

Objective: To assess soluble and surface IL-5Rα levels in patients with EO and/or mastocytosis.

Myeloid dysplasia and bone marrow hypocellularity in adenosine deaminase-deficient severe combined immune deficiency.

Genetic deficiency of adenosine deaminase (ADA) can cause profound lymphopenia and result in the clinical presentation of severe combined immune deficiency (SCID). However, because of the ubiquitous expression of ADA, ADA-deficient patients often present also with nonimmunologic clinical problems, affecting the skeletal, central nervous, endocrine, and gastrointestinal systems. We now report that myeloid dysplasia features and bone marrow hypocellularity are often found in patients with ADA-SCID.

Evaluation of methods for urine inhibitory potential for precipitation of calcium oxalate.

Renal lithiasis is a significant medical and social problem. Worldwide recurrence is anywhere from 3% to 5%. Objective of this paper is to evaluate two methods for distinguishing between stone formers and non-stone formers.

Myelodysplasia in autosomal dominant and sporadic monocytopenia immunodeficiency syndrome: diagnostic features and clinical implications.

A novel, genetic immunodeficiency syndrome has been recently described, herein termed "MonoMAC". It is characterized by severe circulating monocytopenia, NK- and B-lymphocytopenia, severe infections with M. avium complex (MAC), and risk of progression to myelodysplasia/acute myelogenous leukemia.

Time trends in Balkan endemic nephropathy incidence in the most affected region in Serbia, 1977-2009: the disease has not yet disappeared.

Background: Balkan endemic nephropathy (BEN) is a familial chronic kidney disease, which occurs only in some regions of the Balkan Peninsula. The aim of this study was to determine the main epidemiological features of BEN in the Kolubara region, the most affected region in Serbia, and to try to elucidate the controversial issue of whether or not BEN is tapering off.

Methods: To evaluate the BEN incidence rates in the municipality of Lazarevac over a 33-year period (1977-2009), we used data of BEN notifications from the BEN Registry located in the Special Hospital for Endemic Nephropathy, Lazarevac.

Beta2-microglobulin and alpha1-microglobulin as markers of Balkan endemic nephropathy, a worldwide disease.

Background:  Urine beta2-microglobulin (beta2-MG) was mainly used as a tubular marker of Balkan endemic nephropathy (BEN) but recently alpha1-microglobulin (alpha1-MG) was proposed for the diagnosis of BEN. In this study, the potential of urine beta2-MG, alpha1-MG, albumin, and total protein in the differentiation of BEN from healthy persons and patients with glomerulonephritis (GN) and nephrosclerosis (NS) was examined.

Methods:  This study involved 47 patients with BEN, 36 with GN, 11 with NS, 30 healthy subjects from BEN families, and 46 healthy subjects from non-BEN families.

Myelomagenesis: capturing early microenvironment changes.

Plasma cell neoplasms result from the clonal expansion of terminally differentiated, immunoglobulin heavy-chain class switched B cells that typically secrete a monoclonal immunoglobulin. The 2008 World Health Organization (WHO) classification of plasma cell neoplasms encompasses a broad spectrum of disorders, from the precursor disorder monoclonal gammopathy of undetermined significance (MGUS) to plasma cell leukemia. The classification includes, in addition to precursor lesion MGUS, plasma cell myeloma, plasmacytoma, immunoglobulin deposition diseases, and osteosclerotic myeloma.

Osteopontin expression correlates with nuclear factor-κB activation and apoptosis downregulation in clear cell renal cell carcinoma.

Osteopontin (OPN) is a phosphoglycoprotein implicated in tumorigenesis and tumor cell metastasis. Apoptosis inhibition is one of the mechanisms that contribute to development and progression of cancer, and might be initiated by OPN interaction with tumor cells. The aim of this study was to analyze the relation between OPN and nuclear factor-kappa B (NF-κB) expression in clear cell renal cell carcinoma (CCRCC), as well as their relation to apoptotic activity of tumor cells.

Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis.

Cooperating genetic events are likely to contribute to the phenotypic diversity of KIT-D816V systemic mastocytosis. In this study, 44 patients with KIT-D816V systemic mastocytosis were evaluated for coexisting NRAS, KRAS, HRAS or MRAS mutations. Activating NRAS mutations were identified in 2 of 8 patients with advanced disease.

Bortezomib resistance in mantle cell lymphoma is associated with plasmacytic differentiation.

Bortezomib induces remissions in 30%-50% of patients with relapsed mantle cell lymphoma (MCL). Conversely, more than half of patients' tumors are intrinsically resistant to bortezomib. The molecular mechanism of resistance has not been defined.

The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL), an incurable malignancy of mature B lymphocytes, involves blood, bone marrow, and secondary lymphoid organs such as the lymph nodes (LN). A role of the tissue microenvironment in the pathogenesis of CLL is hypothesized based on in vitro observations, but its contribution in vivo remains ill-defined. To elucidate the effects of tumor-host interactions in vivo, we purified tumor cells from 24 treatment-naive patients.

Gray platelet syndrome: natural history of a large patient cohort and locus assignment to chromosome 3p.

Gray platelet syndrome (GPS) is an inherited bleeding disorder characterized by macrothrombocytopenia and absence of platelet α-granules resulting in typical gray platelets on peripheral smears. GPS is associated with a bleeding tendency, myelofibrosis, and splenomegaly. Reports on GPS are limited to case presentations.

Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19.

Adoptive transfer of genetically modified T cells is an attractive approach for generating antitumor immune responses. We treated a patient with advanced follicular lymphoma by administering a preparative chemotherapy regimen followed by autologous T cells genetically engineered to express a chimeric antigen receptor (CAR) that recognized the B-cell antigen CD19. The patient's lymphoma underwent a dramatic regression, and B-cell precursors were selectively eliminated from the patient's bone marrow after infusion of anti-CD19-CAR-transduced T cells.

An interleukin-6-related systemic inflammatory syndrome in patients co-infected with Kaposi sarcoma-associated herpesvirus and HIV but without Multicentric Castleman disease.

Background: Kaposi sarcoma-associated herpesvirus (KSHV) is the causal agent for Kaposi sarcoma (KS) and multicentric Castleman disease (MCD) in human immunodeficiency virus (HIV)-infected patients. Patients with KSHV-MCD develop fevers, wasting, hypoalbuminemia, cytopenias, and hyponatremia that are related to overproduction of KSHV-encoded viral interleukin (IL)-6 (vIL-6) and human IL-6 (hIL-6).

Methods: We identified 6 HIV-infected patients with KS or serological evidence of KSHV infection who had severe inflammatory MCD-like symptoms but in whom we could not diagnose MCD, and we hypothesized that these symptoms resulted from vIL-6 overproduction.

[Investigation of Balkan endemic nephropathy in Serbia: how to proceed?].

Balkan endemic nephropathy (BEN) presents an unsolved puzzle despite fifty years of its investigation. Academy of Medical Sciences of the Serbian Medical Society organized a round table discussion on current unsolved problems related to BEN. The present paper summarizes presentations, discussion and conclusions of this meeting.

Paraneoplastic granulocytosis in metastatic melanoma.

Paraneoplastic syndromes are an uncommon, yet well-described, phenomenon in cancer patients. The syndrome of granulocytosis caused by granulocyte colony-stimulating factor (G-CSF) production by tumors is rare and is difficult to diagnose in patients receiving treatment for metastatic disease. From January 2005 to May 2009, 626 patients were evaluated for treatment of metastatic melanoma.

Are lipoprotein disturbances in chronic hemodialyzed patients only renal failure related?

Chronically hemodialyzed (HD) patients frequently suffer from quantitative and even more often qualitative serum lipids disorders. Mostly they have increased triglycerides and VLDL-cholesterol, slightly increased or normal total and LDL-cholesterol and decreased HDL-cholesterol concentrations. The study compared lipid profile between two groups of chronic HD patients coming from regionally distinct areas, the continental and the maritime one.

How activity of inflammatory bowel disease influences bone loss.

Bone loss is a common problem for individuals with inflammatory bowel disease (IBD). The aim of our study was to assess bone mineral density (BMD) in patients with IBD and to investigate the role of corticosteroid (CS) use and duration and activity of disease on BMD. Ninety-two patients (56 men and 36 women) with IBD, of whom 32 had ulcerative colitis (UC) and 60 had Crohn's disease (CD), underwent clinical assessment.

Repetitive busulfan administration after hematopoietic stem cell gene therapy associated with a dominant HDAC7 clone in a nonhuman primate.

The risk of genotoxicity of retroviral vector-delivered gene therapy targeting hematopoietic stem cells (HSCs) has been highlighted by the development of clonal dominance and malignancies in human and animal gene therapy trials. Large-animal models have proven invaluable to test the safety of retroviral vectors, but the detection of clonal dominance may require years of follow-up. We hypothesized that hematopoietic stress may accelerate the proliferation and therefore the detection of abnormal clones in these models.

Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy.

Purpose: Interleukin-7 (IL-7) has critical and nonredundant roles in T-cell development, hematopoiesis, and postdevelopmental immune functions as a prototypic homeostatic cytokine. Based on a large body of preclinical evidence, it may have multiple therapeutic applications in immunodeficiency states, either physiologic (immunosenescence), pathologic (HIV), or iatrogenic (postchemotherapy and posthematopoietic stem cell transplant), and may have roles in immune reconstitution or enhancement of immunotherapy. We report here on the toxicity and biological activity of recombinant human IL-7 (rhIL-7) in humans.

Today Balkan endemic nephropathy is a disease of the elderly with a good prognosis.

Background: The outcome for Balkan endemic nephropathy (BEN) patients diagnosed in 1992 was analyzed in 2006 with the aim of detecting factors associated with disease progression and patient outcome.

Methods: In 1992 BEN was detected in 119 patients (53 males, 56.9 +/- 13.

Pediatric-onset mastocytosis: a long term clinical follow-up and correlation with bone marrow histopathology.

Background: Pediatric onset mastocytosis usually presents as urticaria pigmentosa; and less often as diffuse cutaneous mastocytosis. While the literature indicates that disease often resolves, there has been a move to more aggressive therapy for mastocytosis early in life. We addressed the long term prognosis of pediatric-onset disease by examining 17 children with mastocytosis which we had reported on in 1989 [1].

Hematologic, biochemical, and cardiopulmonary effects of L-arginine supplementation or phosphodiesterase 5 inhibition in patients with sickle cell disease who are on hydroxyurea therapy.

Objectives: Fetal hemoglobin (HbF) induction involves NO-cGMP signaling pathways. L-arginine, an NO precursor, and the phosphodiesterase (PDE) 5 inhibitor sildenafil, which potentiates cGMP, were studied in adults with sickle cell disease (SCD) who were stably on HU.

Methods: Twenty four courses of L-arginine (0.

Efficacy of hyperphosphatemia control in the progression of chronic renal failure and the prevalence of cardiovascular calcification.

Background And Aims: Chronic kidney disease mineral- and bone disorder (CKD-MBD) has been studied more often in dialysis than in predialysis CKD patients. The association between efficacy of hyperphosphatemia control and chronic renal failure (CRF) progression, prevalence of bone disease and cardiovascular calcification was the objective of the present investigation.

Material And Methods: 42 patients with CKD in Stage 5, regularly monitored for 5 years, were divided into Group 1 of 20 patients with normal serum phosphate (sPO4) levels and Group 2 of 22 patients with hyperphosphatemia registered at the majority of checks.