Publications by authors named "Dan Avi Landau"

Activation of regulatory elements is thought to be inversely correlated with DNA methylation levels. However, it is difficult to determine whether DNA methylation is compatible with chromatin accessibility or transcription factor (TF) binding if assays are performed separately. We developed a fast, low-input, low sequencing depth method, EpiMethylTag, that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA.

View Article and Find Full Text PDF

Bone consists of separate inner endosteal and outer periosteal compartments, each with distinct contributions to bone physiology and each maintaining separate pools of cells owing to physical separation by the bone cortex. The skeletal stem cell that gives rise to endosteal osteoblasts has been extensively studied; however, the identity of periosteal stem cells remains unclear. Here we identify a periosteal stem cell (PSC) that is present in the long bones and calvarium of mice, displays clonal multipotency and self-renewal, and sits at the apex of a differentiation hierarchy.

View Article and Find Full Text PDF

Comparison of sequencing data from a tumor sample with data from a matched germline control is a key step for accurate detection of somatic mutations. Detection sensitivity for somatic variants is greatly reduced when the matched normal sample is contaminated with tumor cells. To overcome this limitation, we developed deTiN, a method that estimates the tumor-in-normal (TiN) contamination level and, in cases affected by contamination, improves sensitivity by reclassifying initially discarded variants as somatic.

View Article and Find Full Text PDF

Large-scale, massively parallel sequencing of human cancer samples has revealed tremendous genetic heterogeneity within individual tumors. Indeed, tumors are composed of an admixture of diverse subpopulations-subclones-that vary in space and time. Here, we discuss a principal driver of clonal diversification in cancer known as chromosomal instability (CIN), which complements other modes of genetic diversification creating the multilayered genomic instability often seen in human cancer.

View Article and Find Full Text PDF

Major international projects are underway that are aimed at creating a comprehensive catalogue of all the genes responsible for the initiation and progression of cancer. These studies involve the sequencing of matched tumour-normal samples followed by mathematical analysis to identify those genes in which mutations occur more frequently than expected by random chance. Here we describe a fundamental problem with cancer genome studies: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds.

View Article and Find Full Text PDF

Background: Donor lymphocyte infusions can induce remissions in patients with relapse after allogeneic hematopoietic stem cell transplantation. Nevertheless, some grafted patients never display any signs of alloreactivity, either following allogeneic hematopoietic stem cell transplantation or after donor lymphocyte infusions. Consequently, they do not develop graft-versus-host disease and frequently do not respond to donor lymphocyte infusions.

View Article and Find Full Text PDF

MicroRNAs (miRNAs) are aiding our understanding of cancer biology, and are now coming close to therapeutic use as well. Here, we focus specifically on the interaction between miRNAs and genomic instability. MiRNA regulation is essential to many cellular processes, and escape from this regulatory network seems to be a common characteristic of malignant transformation.

View Article and Find Full Text PDF

Recipient-specific regulatory T cells (rsTreg) can prevent graft-versus-host disease (GVHD) by inhibiting donor T-cell expansion after hematopoietic stem cell transplantation (HSCT) in mice. Importantly, in adult humans, because of thymus involution, immune reconstitution during the first months after HSCT relies on the peripheral expansion of donor T cells initially present in the graft. Therefore, we developed a mouse model of HSCT that excludes thymic output to study the effect of rsTreg on immune reconstitution derived from postthymic mature T cells present within the graft.

View Article and Find Full Text PDF

The subpopulation of regulatory T cells (Treg) was shown to play a key role in alloreactive responses. In allogeneic hematopoietic stem cell transplantation, several groups tested whether Treg content in transplants correlates with graft-versus-host disease (GVHD) with controversial results. In a retrospective study of 49 consecutive HLA-matched sibling transplantations, we studied the relationship between Treg content in bone marrow transplants and acute GVHD (aGVHD) occurrence.

View Article and Find Full Text PDF

Objective: Hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) vasculitis is an autoimmune disorder with significant morbidity and mortality. Renal involvement was associated with an increased mortality, and was the most common cause of death; these data were obtained before effective antiviral treatment was available. We studied causes of death and predictive factors in patients with HCV-associated MC vasculitis treated with antivirals.

View Article and Find Full Text PDF

Background: On 21 June 2005, a passenger train collided with a truck near Revadim, Israel. The collision resulted in a multiple-scene mass-casualty incident in an area characterized by difficult access and a relatively long distance from trauma centers. A major disaster response was initiated by civilian and military medical forces including the Israeli Air Force (IAF) Search and Rescue teams.

View Article and Find Full Text PDF

Objective: Mixed cryoglobulinemia (MC) vasculitis is an autoimmune disorder associated with chronic hepatitis C virus (HCV) infection. We previously reported that MC vasculitis is associated with a quantitative defect of peripheral blood regulatory T cells. The aim of this study was to prospectively evaluate the evolution of this defect during the course of antiviral treatment.

View Article and Find Full Text PDF

Objective: The objectives of this study were to describe gastrointestinal (GI) disease prevalence in Israeli adolescents, and possible associations between prevalence and body mass index (BMI), sex and Jewish ethnicity.

Design: A retrospective analysis of screening for GI disease performed by the Israeli Defense Forces recruiting office between 1998 and 2003.

Setting: Screening was performed at the recruiting office, and included detailed history and physical examination performed by a general practitioner.

View Article and Find Full Text PDF

Background: We evaluated particulate matter in combined induced sputum (IS) and oxidation in exhaled breath condensate (EBC) to test whether underlying inflammatory changes are present in asymptomatic welders.

Methods: Thirty welders from the Israel Defense Forces exposed to aluminum/iron (Group 1) or to cadmium/chromium/iron/lead/nickel (Group 2, N = 16) and 27 non-exposed administrators were studied. IS was recovered, particle size distribution, hydrogen peroxide and pH were measured, and exhaled breath condensate was collected.

View Article and Find Full Text PDF

Objective: To investigate the clinical characteristics, outcomes, and results of hepatitis C virus (HCV) RNA analyses in a group of patients with HCV-associated mixed cryoglobulinemia (MC) vasculitis who experienced a relapse of vasculitis despite achieving a sustained viral response to treatment with antiviral agents.

Methods: HCV RNA testing was performed by the transcription-mediated amplification (TMA) method in sera and cryoprecipitates (detection limit 2.5 IU/ml).

View Article and Find Full Text PDF

Background And Aims: In the past 20 years, a growing proportion of new cases of celiac disease (CD) are diagnosed in adults and in patients with extraintestinal manifestations. Our understanding of the extremely wide spectra of manifestations and the profound effects on elderly patients is improving. Nevertheless, CD is still underdiagnosed in elderly patients.

View Article and Find Full Text PDF

Hepatitis C virus (HCV) has been shown in epidemiologic studies to be associated with immune system disorders. Primarily disorders that stem from B-cell regulatory control disturbance, such as mixed cryoglobulinemia (MC) and non-Hodgkin's lymphoma (NHL). The causative role of HCV in these disorders is supported by the response to anti-viral treatment.

View Article and Find Full Text PDF

Visit length (VL) has been decreasing over the last decades. Patients and physicians alike hold that this may have adverse affects on quality of care and patient-doctor rapport. Our aim was to study the optimal VL as viewed by the patients as well as possible related factors such as demographicparameters and patient satisfaction.

View Article and Find Full Text PDF

Background And Aims: Cardiovascular screening in young adults is an important tool in many occupational settings. Our aim was to test whether screening physical examination and ECG influence the rate of abnormal echocardiogarphic findings in young healthy subjects.

Methods: Consecutive echocardiography results of 18- to 20-year-old flight candidates were analyzed retrospectively.

View Article and Find Full Text PDF

Background And Aims: Liver diseases are associated with significant morbidity and health- related expenditure. Although cost-effective treatments are available, the disease is often asymptomatic until late in its course. "Medex Test," is the noninvasive detection of liver abnormalities by the measurement of changes in electrical impedance of dermal zones.

View Article and Find Full Text PDF

Background And Aims: Acute hepatitis C virus infection in the era of universal screening of blood products has not disappeared, and is thought to be transmitted primarily via injecting drug use. A growing body of evidence supports iatrogenic transmission as an important mode of transmission. The aim of this study was to examine transmission routes and clinical characteristics in a group of patients with acute hepatitis C in Israel.

View Article and Find Full Text PDF

Survival rates from childhood cancer have dramatically improved over the past three decades; average overall 5-yr survival rates are now > 75%. However, this has been achieved by treatments associated with significant morbidity that may present many years later. This review seeks to delineate the basic information necessary to evaluate flight-training candidates with a history of childhood cancer.

View Article and Find Full Text PDF

Background & Aims: Neck pain and lower back pain (LBP) are frequently reported by military helicopter pilots (HP) and fighter pilots. A small number of studies have used imaging methods to evaluate spinal cervical degenerative findings in pilots exposed to high +Gz, with results indicating an increase in cervical disk protrusions in this population. We evaluated the cervical and lumbar spine with magnetic resonance imaging (MRI) to assess the prevalence of degenerative changes in three subpopulations of pilots.

View Article and Find Full Text PDF

Medicine is undergoing profound change, but the basic format of the medical encounter has remained unchanged. Nevertheless, medicine in the 22nd century may be fully computerized, and a possible model is shortly depicted in this paper. Computer applications are constantly increasing their share in medical diagnosis, and may ultimately replace physicians.

View Article and Find Full Text PDF