David Hassin

Assuta Medical Center

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Gideon Berke

Weizmann Institute of Science

Boaz Avidor

Tel Aviv Sourasky Medical Center

O. Gal-Garber

Hebrew University of Jerusalem

Ruhama Fixler

Poriya Medical Center

Yonathan Hasin

Ariel University

Dan Turner

Shaare Zedek Medical Center

Sara Lavi

Tel Aviv University

Shulamit Karby

Tel Aviv University

Ziv Sevilya

Ben-Gurion University of the Negev

Harvey L. Bank

Medical University of South Carolina

Cooperative Institutions

Tel Aviv University

Sheba Medical Center

Tel Aviv Sourasky Medical Center

Rabin Medical Center

Hebrew University of Jerusalem

Weizmann Institute of Science

Hadassah Medical Center

Ben-Gurion University of the Negev

Wolfson Medical Center

Technion – Israel Institute of Technology

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“U-Turn” Replication at Arrested Forks Leads to the Generation of Extrachromosomal Inverted Repeats

CRC Press eBooks (2020)

Sara Lavi David Hassin Mirit I. Aladjem Zlil Ophir Shulamit Karby

Gene amplification is commonly observed in malignant cells and in drug-resistant cell lines. It is a dynamic process in which the structures generated early are altered during cell propagation or drug selection. Amplified sequences are often detected as paired acentric circular structures called double minute chromosomes, or as expanded chromosomal regions. To investigate the molecular mechanisms governing the amplification process, the authors constructed a model system consisting of an integrated SV40 genome in virally transformed Chinese hamster cells. Damaged template, modified DNA, nicks, triple-helix structures, sequences with specific conformation, and protein–DNA complexes might arrest the advancement of the replication fork and could lead to U-turn replication. The newly generated hairpin structures might recombine into the chromosome, yielding chromosomally associated inverted repeat duplications.

Extrachromosomal DNA

Inverted repeat

Replication

10.1201/9781003066989-43

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Urinary tract infection in patients with urethral stents

CRC Press eBooks (2004)

David Hassin V Istomin B. Shohat M Kaufstein Daniel Yachia

10.3109/9780203427910-24

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Cytotoxic T lymphocyte perforin and Fas ligand working in concert even when Fas ligand lytic action is still not detectable

Immunology (2011)

David Hassin Orit Gal Garber Avihai Meiraz Yael S. Schiffenbauer Gideon Berke

The reason(s) why individual cytotoxic T lymphocytes (CTL) possess a fast-acting, perforin/granzyme-mediated, as well as a much slower, Fas ligand (FasL) -driven killing mechanism is not clear, nor is the basis for wide variations in killing activity exhibited by individual CTL, ranging from minutes to hours. We show that perforin expression among individual, conjugated CTL varies widely, which can account for the heterogeneity in killing speeds exhibited by individual CTL. Despite a 2-hr lag in FasL-based killing, CTL lytic action is enhanced when the two mechanisms operate in concert. This is explained by finding that the two pathways in fact are jump-started simultaneously with the lag in FasL lytic action reflecting pre-lytic caspase-8 activation and BH3-interacting domain (BID) cleavage. The complementary action of the two lytic pathways, co-expressed at varying levels among individual CTL, facilitates the lytic action of late-stage poor perforin-expressing CTL, ensuring optimal cytocidal action throughout the CTL response.

CTL*

Lytic cycle

Fas ligand

Granzyme

10.1111/j.1365-2567.2011.03426.x

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Citations (99)

Killing of Latently HIV-Infected CD4 T Cells by Autologous CD8 T Cells Is Modulated by Nef

Frontiers in Immunology (2018)

Ziv Sevilya Ehud Chorin O. Gal-Garber Einat Zelinger Dan Turner

The role of HIV-specific CD8 T cell activity in the course of HIV infection and the way it affects the virus that resides in the latent reservoir resting memory cells is debated. The PBMC of HIV-infected patients contain HIV-specific CD8 T cells and their potential targets, CD4 T cells latently infected by HIV. CD4 T cells and CD8 T cells procured from PBMC of HIV-infected patients were co-incubated and analyzed: Formation of CD8 T cells and HIV-infected CD4 T cell conjugates and apoptosis of these CD4 T cells were observed by fluorescence microscopy with in situ PCR of HIV LTR DNA. Furthermore, conjugation of CD8 T cells with CD4 T cells and apoptosis of CD4 T cells was observed and quantified by imaging flow cytometry using anti-human activated caspase 3 antibody and TUNEL assay. The conjugation activity and apoptosis were found to be much higher in patients with acute HIV infection or AIDS compared to patients in chronic infection on antiretroviral therapy (ART) or not. Patients on ART had low grade conjugation and apoptosis of isolated CD69, CD25, and HLA-DR-negative CD4 T cells (latent reservoir cells) by CD8 T cells. Using in situ PCR The latent reservoir CD4 T cells were shown to contain most of the HIV DNA. We demonstrate in HIV-infected patients, that CD8 T cells conjugate with and kill HIV-infected CD4 T cells, including HIV-infected resting memory CD4 T cells, throughout the course of HIV infection. We propose that in HIV-infected patients CD4 T cell annihilation is caused in part by ongoing activity of HIV-specific CD8 T cells. HIV Nef protein interacts with ASK 1 and inhibits its pro-apoptotic death signaling by Fas/FasL, thus protecting HIV-infected cells from CD8 T cells killing. A peptide that interrupts Nef-ASK1 interaction that had been delivered into CD4 T cells procured from patients on ART resulted in the increase of their apoptosis inflicted by autologous CD8 T cells. We suggest that elimination of the HIV-infected latent reservoir CD4 T cells can be achieved by Nef inhibition.

10.3389/fimmu.2018.02068

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Developing and implementing a model for changing physicians' prescribing habits - the role of clinical pharmacy in leading the change

Journal of Clinical Pharmacy and Therapeutics (2006)

Eyal Schwartzberg S. Rubinovich David Hassin J. Haspel A. Ben-Moshe

Budgetary constraints led the Israeli Hillel Yaffe Medical Center management to implement policies for reducing expenditure while maintaining the quality of care. For this purpose, the pharmacy services management developed and implemented a three-tier intervention feedback model for changing physicians' prescribing habits, and achieving cost-effective changes in antibiotic utilization.A prospective drug utilization evaluation was conducted to profile antibiotic utilization. The results established a base from which a three-tier feedback, evidence-based intervention model was built. This model corresponds to the following three hierarchical levels: Level 1 activities involved management actions that influenced all levels of staff and concentrated mainly on the creation of guidelines. Level 2 activities involved the reorganization of the restricted antibiotics prescription authorization system, through the co-operation of the clinical pharmacy unit and the hospital infection control specialist. Level 3 focussed on clinical pharmacist activities on the wards. The model was implemented and assessed in the hospital from June 2002 until December 2004.Implementation of the model resulted in a cumulative decrease of 6,473 i.v. antibiotics daily defined doses (DDDs) and a parallel increase in total oral antibiotic DDDs (Table 1). These changes were especially notable with high-bioavailability antibiotics and co-amoxiclav, where over 2.5 years there was a reduction of 2,472 and 4,752 i.v. DDDs, respectively (P < 0.000). The successful implementation of the model resulted in a reduction of 375,000 NIS ( approximately 66,190 euro) in pharmacy antibiotic costs, equivalent to 10 i.v. DDDs or 570 NIS ( approximately 102 euro) saved per clinical pharmacist working day.Our study demonstrates the successful implementation of a three-tier model for changing physicians' antibiotic prescribing.

Defined daily dose

10.1111/j.1365-2710.2006.00724.x

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Citations (24)

Carcinogen-Induced DNA Amplification In Vitro: Overreplication of the Simian Virus 40 Origin Region in Extracts from Carcinogen-Treated CO60 Cells

Molecular and Cellular Biology (1990)

Yehudit Berko-Flint Shulamit Karby David Hassin Sara Lavi

An in vitro system to study carcinogen-induced amplification in simian virus 40 (SV40)-transformed Chinese hamster (CO60) cells is described. SV40 amplification in this system resembled in many aspects the viral overreplication observed in drug-treated CO60 cells. Cytosolic extracts from N-methyl-N'-nitro-N-nitrosoguanidine-treated cells supported de novo DNA synthesis in the presence of excess exogenous T antigen and the SV40-containing plasmid pSVK1. The pattern of viral replication in these extracts was unique, since only the 2.4-kilobase-pair region spanning the origin was overreplicated, whereas distal sequences were not replicated significantly. Extracts from control cells supported only marginal levels of replication. In HeLa extracts, complete SV40 DNA molecules were replicated efficiently. The overreplication of the origin region in CO60 cell extracts was bidirectional and symmetrical. A fraction of the newly synthesized DNA molecules underwent a second round of replication, yielding MboI-sensitive fragments representing the 2.4-kilobase-pair region around the origin. The mechanisms controlling the amplification of the viral origin region, the nature of the cellular factors induced in the carcinogen-treated cells, and their putative association with general drug-induced SOS-like responses are discussed.

HeLa

Simian

10.1128/mcb.10.1.75-83.1990

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Citations (1)

Agranulocytosis associated with parvovirus B19 infection in otherwise healthy patients

European Journal of Internal Medicine (2004)

Valery Istomin E. Guven Sade Zahava Grossman H Rudich Orit Sofer

Leukopenia

10.1016/j.ejim.2004.11.002

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Citations (24)

Pacemaker Endocarditis Report of 44 Cases and Review of the Literature

Medicine (1994)

Nadir Arber Elon Pras Yitschak Copperman Jonathan M. Schapiro Vardiela Meiner

Arber, Nadir M.D.; Pras, Elon M.D.; Copperman, Yitschak M.R.C.P.I.; Schapiro, Jonathan M. M.D.; Meiner, Vardiela M.D.; Lossos, Izidore S. M.D.; Militianu, Arie M.D.; Hassin, David M.D.; Pras, Eran B.Sc; Shai, Avi M.D.; Moshkowitz, Menachem M.D.; Sidi, Yechezkel M.D. Author Information

10.1097/00005792-199411000-00003

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Citations (256)

The use of systemic antibiotics in seven community hospitals in Northern Israel

Journal of Infection (1998)

Raanan Raz Y. Farbstein David Hassin R Kitzes Dan Miron

Systemic antibiotics

10.1016/s0163-4453(98)91890-4

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Citations (11)

Approach to the Patient with Fever: Acute Febrile Illness

Clinical Infectious Diseases (1998)

Ethan Rubinstein David Hassin

Abstract Acute febrile illnesses usually develop within a 24 h period, and either subside in a few days (e.g., viral upper respiratory tract infection [URI]) or, because of their severity or associated symptoms, lead to early medical evaluation and diagnosis. While any process that can cause fever may have an acute onset and could involve a wide variety of infectious, inflammatory, or other disorders (Chapter 10), the vast majority of acute febrile illnesses are due to infection (Table 47.1). Chronic febrile illnesses, i.e., those lasting several weeks, often have a subtle onset; they may be more difficult to diagnose, and when infectious that are most often caused by pathogens that are sheltered from host defenses (e.g., intracellular or in abscesses, bone, or endocardium).

Acute illness

Endocardium

10.1093/oso/9780195081039.003.0047

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