Poorer outcome of childhood acute lymphoblastic leukemia in the Bedouin population: A report from the Berlin-Frankfurt-Muenster-based Israeli national protocols.

Background: Therapy outcomes for childhood acute lymphoblastic leukemia (ALL) had substantially improved in the last decades, but variability across racial and ethnic groups was identified in some clinical studies. In this study, we aimed to investigate whether such a difference in outcome is found in the diverse ethnicities in Israel as well.

Methods: A retrospective study was conducted among 1154 patients (855 Jews, 195 Muslims, 52 Bedouins, 26 Druze, and 26 others) aged 1 to 21 years, who were diagnosed with ALL between 1989 and 2011 and were treated according to the same Berlin-Frankfurt-Muenster-based Israel National Study protocols.

Expression of a recombinant, 4'-Phosphopantetheinylated, active M. tuberculosis fatty acid synthase I in E. coli.

Background: Fatty acid synthase 1 (FAS I) from Mycobacterium tuberculosis (Mtb) is an essential protein and a promising drug target. FAS I is a multi-functional, multi-domain protein that is organized as a large (1.9 MDa) homohexameric complex.

AcpM, the meromycolate extension acyl carrier protein of Mycobacterium tuberculosis, is activated by the 4'-phosphopantetheinyl transferase PptT, a potential target of the multistep mycolic acid biosynthesis.

Modification of acyl carrier proteins (ACP) or domains by the covalent binding of a 4'-phosphopantetheine (4'-PP) moiety is a fundamental condition for activation of fatty acid synthases (FASes) and polyketide synthases (PKSes). Binding of 4'-PP is mediated by 4' phosphopantetheinyl transfersases (PPTases). Mycobacterium tuberculosis (Mtb) possesses two essential PPTases: acyl carrier protein synthase (Mtb AcpS), which activates the multidomain fatty acid synthase I (FAS I), and Mtb PptT, an Sfp-type broad spectrum PPTase that activates PKSes.

Spinal cord stimulation attenuates temporal summation in patients with neuropathic pain.

Evidence has shown that electrical stimulation at the dorsal columns attenuated the "wind-up" phenomenon in dorsal horn neurons in nerve-injured rats. This study was aimed to test the effect of spinal cord stimulation (SCS) on temporal summation (TS), the clinical correlate of the wind-up phenomenon in patients with radicular leg pain. Eighteen patients with SCS implants were tested both 30 minutes after SCS activation ("ON") and 2 hours after turning it off ("OFF"), in a random order.

Briefly trained medical students can effectively identify rheumatic mitral valve injury using a hand-carried ultrasound.

Background: Rheumatic heart disease (RHD) is common and remains a major cause of morbidity, particularly in developing countries. Its diagnosis relies on expertise-dependent echocardiographic studies. We evaluated the accuracy of briefly trained examiners in identifying RHD utilizing a hand-carried cardiac ultrasound (HCU) device.

Treatment of T cell lymphoblastic lymphoma in children and adolescents: Israel Society of Pediatric Hematology Oncology retrospective study.

Background: Survival in T cell lymphoblastic lymphoma has improved over the past 30 years, largely due to treatment protocols derived from regimens designed for children with acute lymphoblastic leukemia.

Objectives: To assess the outcome of the NHL-BFM-95 protocol in children and adolescents hospitalized during the period 1999-2006.

Methods: We conducted a retrospective multi-institutional, non-randomized study of children and adolescents up to age 21 with T cell lymphoma admitted to pediatric departments in six hospitals in Israel, with regard to prevalence, clinical characteristics, pathological characteristics, prognostic factors, overall survival (OS) and event-free survival (EFS).

Upfront use of gemtuzumab ozogamicin in young children with CD33-positive AML.

Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 antibody used for treating patients with CD33+ acute myeloid leukemia (AML). We report three young children (two infants and one toddler) with AML treated with GO 9 mg/m(2). Two received two doses at diagnosis alone with conventional chemotherapy and one received one dose after relapse.

Biochemical and structural properties of chimeras constructed by exchange of cofactor-binding domains in alcohol dehydrogenases from thermophilic and mesophilic microorganisms.

The cofactor-binding domains (residues 153-295) of the alcohol dehydrogenases from the thermophile Thermoanaerobacter brockii (TbADH), the mesophilic bacterium Clostridium beijerinckii (CbADH), and the protozoan parasite Entamoeba histolytica (EhADH1) have been exchanged. Three chimeras have been constructed. In the first chimera, the cofactor-binding domain of thermophilic TbADH was replaced with the cofactor-binding domain of its mesophilic counterpart CbADH [chimera Chi21((TCT))].

Structure-function analysis of the acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis.

We have solved the crystal structure of the acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis (Mtb) at 1.95 A resolution. AcpS, a 4-phosphopantetheinyl transferase, activates two distinct acyl carrier proteins (ACPs) that are present in fatty acid synthase (FAS) systems FAS-I and FAS-II, the ACP-I domain and the mycobacterial ACP-II protein (ACPM), respectively.

Extended triple intrathecal therapy in children with T-cell acute lymphoblastic leukaemia: a report from the Israeli National ALL-Studies.

Owing to the increased central nervous system (CNS) relapse risk in T-cell acute lymphoblastic leukaemia (ALL), it is unclear whether preventive cranial radiation (pCRT) can be safely omitted. In this study, pCRT was replaced by extended triple intrathecal therapy (TIT) in prednisone good early responders - medium-risk (MR) group, accounting for 76% of T-ALL patients. From 1989 to 2003, 143 T-ALL patients aged 1-18 years were enrolled in the Israel National Studies (INS) 89 (n = 84) and INS 98 (n = 59) trials, based on ALL-Berlin-Frankfurt-Munster (BFM) 86/90 and ALL-BFM 95 protocols, respectively.

Burkitt lymphoma in children: the Israeli experience.

Background: We analyzed the results of the French-American-British-LMB 96 protocol performed in 9 centers in Israel on 88 patients with B-cell non-Hodgkin lymphoma treated from 2000 to 2005.

Procedure: The majority of the patients was male (63/88, 72%), with a median age of 8.9 years (range, 2.

Thermal stabilization of the protozoan Entamoeba histolytica alcohol dehydrogenase by a single proline substitution.

Analysis of the three-dimensional structures of two closely related thermophilic and hyperthermophilic alcohol dehydrogenases (ADHs) from the respective microorganisms Entamoeba histolytica (EhADH1) and Thermoanaerobacter brockii (TbADH) suggested that a unique, strategically located proline residue (Pro275) at the center of the dimerization interface might be crucial for maintaining the thermal stability of TbADH. To assess the contribution of Pro275 to the thermal stability of the ADHs, we applied site-directed mutagenesis to replace Asp275 of EhADH1 with Pro (D275P-EhADH1) and conversely Pro275 of TbADH with Asp (P275D-TbADH). The results indicate that replacing Asp275 with Pro significantly enhances the thermal stability of EhADH1 (DeltaT(1/2) View Article and Find Full Text PDF

Shwachman--Diamond syndrome associated with autoimmune phenomena.

A 2-year-old boy was evaluated for failure to thrive, hypotonia and developmental delay. The child exhibited all the criteria of Shwachman-Diamond syndrome, i.e.

A single proline substitution is critical for the thermostabilization of Clostridium beijerinckii alcohol dehydrogenase.

Analysis of the three-dimensional structures of three closely related mesophilic, thermophilic, and hyperthermophilic alcohol dehydrogenases (ADHs) from the respective microorganisms Clostridium beijerinckii (CbADH), Entamoeba histolytica (EhADH1), and Thermoanaerobacter brockii (TbADH) suggested that a unique, strategically located proline residue (Pro100) might be crucial for maintaining the thermal stability of EhADH1. To determine whether proline substitution at this position in TbADH and CbADH would affect thermal stability, we used site-directed mutagenesis to replace the complementary residues in both enzymes with proline. The results showed that replacing Gln100 with proline significantly enhanced the thermal stability of the mesophilic ADH: DeltaT(1/2) (60 min) = + 8 degrees C (temperature of 50% inactivation after incubation for 60 min), DeltaT(1/2) (CD) = +11.

Integrated 18F-fluorodeoxyglucose positron emission tomography and computerized tomography in endodermal sinus tumor.

Application of an in-line positron emission tomography and computerized tomography (PET-CT) in endodermal sinus tumor (EST) is described in this study. CASE 1: A young female with massive ascites postovarian mass resection had elevated alpha-fetoprotein (AFP) serum levels. Following a positive PET-CT study with increased (18)F-fluorodeoxyglucose (FDG) uptake, a CT-guided core biopsy of a peritoneal mass was performed.

Role of 18F-FDG PET/CT in staging and follow-up of lymphoma in pediatric and young adult patients.

Objective: To assess the role of 18F-Fluorodeoxyglucose (18F-FDG) PET/CT in pediatric patients with Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL).

Materials And Methods: 31 patients, mean age 12.9 +/- 5.

Structure of alcohol dehydrogenase from Entamoeba histolytica.

The structure of the apo form of alcohol dehydrogenase from a single-cell eukaryotic source, Entamoeba histolytica, has been determined at 1.8 A. To date, bacterial and archeal alcohol dehydrogenases, which are biologically active as tetramers, have crystallized with tetramers in the asymmetric unit.

Epidermal growth factor receptor gene amplification and expression in disseminated pediatric low-grade gliomas.

Object: Pediatric low-grade gliomas (LGGs) are the largest group of central nervous system neoplasms in children. Although these tumors are generally benign, 5 to 10% of patients with pediatric LGGs present with leptomeningeal dissemination. The genetic and biological nature of these tumors is poorly understood.

Three-dimensional structure determination of proteins related to human health in their functional context at The Israel Structural Proteomics Center (ISPC). This paper was presented at ICCBM10.

The principal goal of the Israel Structural Proteomics Center (ISPC) is to determine the structures of proteins related to human health in their functional context. Emphasis is on the solution of structures of proteins complexed with their natural partner proteins and/or with DNA. To date, the ISPC has solved the structures of 14 proteins, including two protein complexes.

Risk of venous thromboembolism in pediatric patients with brain tumors.

Background: Venous thromboembolism (VTE) is a common event in adults with malignant brain tumors approaching 24% throughout the course of the disease. The high morbidity and mortality of this complication yielded several protocols for prevention of the disease in adults undergoing neurosurgery for brain tumors and possible primary prevention afterwards. We investigated the incidence and complications of VTE in pediatric neuro-oncology patients.

Higher metal-ligand coordination in the catalytic site of cobalt-substituted Thermoanaerobacter brockii alcohol dehydrogenase lowers the barrier for enzyme catalysis.

Thermoanaerobacter brockii alcohol dehydrogenase (TbADH) is a zinc-dependent NADP(+)/H-linked class enzyme that reversibly catalyzes the oxidation of secondary alcohols to their corresponding ketones. Cobalt substitution studies of other members of the alcohol dehydrogenase (ADH) family showed that the cobalt-containing ADHs have a similar active site structure but slightly decreased activity compared to wild-type zinc ADHs. In contrast, the cobalt-substituted TbADH (Co-TbADH) exhibits an increase in specific activity compared to the native enzyme [Bogin, O.

The ternary complex of Pseudomonas aeruginosa alcohol dehydrogenase with NADH and ethylene glycol.

Pseudomonas aeruginosa alcohol dehydrogenase (PaADH; ADH, EC 1.1.1.

Combined cytogenetic and array-based comparative genomic hybridization analyses of Wilms tumors: amplification and overexpression of the multidrug resistance associated protein 1 gene (MRP1) in a metachronous tumor.

Tumor samples from a variety of Wilms tumors (WT) obtained from three patients were analyzed by cytogenetic and array-based comparative genomic hybridization (CGH) methods. The tumors represented different stages of tumorigenesis and included a unilateral primary WT and contralateral nephrogenic rest (case 1), a primary WT and a contralateral metachronous WT (case 2), and a recurrent WT with lung metastases (case 3). All six specimens exhibited abnormal karyotypes characteristic of different WT levels of progression.

Structural basis for the enhanced thermal stability of alcohol dehydrogenase mutants from the mesophilic bacterium Clostridium beijerinckii: contribution of salt bridging.

Previous research in our laboratory comparing the three-dimensional structural elements of two highly homologous alcohol dehydrogenases, one from the mesophile Clostridium beijerinckii (CbADH) and the other from the extreme thermophile Thermoanaerobacter brockii (TbADH), suggested that in the thermophilic enzyme, an extra intrasubunit ion pair (Glu224-Lys254) and a short ion-pair network (Lys257-Asp237-Arg304-Glu165) at the intersubunit interface might contribute to the extreme thermal stability of TbADH. In the present study, we used site-directed mutagenesis to replace these structurally strategic residues in CbADH with the corresponding amino acids from TbADH, and we determined the effect of such replacements on the thermal stability of CbADH. Mutations in the intrasubunit ion pair region increased thermostability in the single mutant S254K- and in the double mutant V224E/S254K-CbADH, but not in the single mutant V224E-CbADH.