Publications by authors named "Dan Sherman"

Cellular stress signals activate adaptive signaling pathways of the mammalian integrated stress response (ISR), of which the unfolded protein response (UPR) is a subset. These pathways converge at the phosporylation of eIF2α. Drug-like, potent and selective chemical inhibitors (valid chemical probes) targeting major ISR kinases have been previously identified, with the exception of GCN2.

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Skp2 is a member of the F-box family of proteins that serve as substrate-specific adaptors in Skp1-CUL1-ROC1-F-box (SCF) E3 ubiquitin ligases. Skp2 (Fbxl1) directly binds to the tumor suppressor p27 in the context of the SCF E3 ubiquitin ligase to ubiquitylate and target-phosphorylated p27 for proteasomal degradation. As p27 is a powerful suppressor of growth in a variety of cells, and as Skp2 is also overexpressed in many human cancers, Skp2 is considered an oncogene and an intriguing drug target.

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Objectives: Patients with cancer often face financial hardships, including loss of productivity, high out-of-pocket (OOP) costs, depletion of savings, and bankruptcy. By providing financial guidance and assistance through specially trained navigators, hospitals and cancer care clinics may be able mitigate the financial burdens to patients and also minimize financial losses for the treating institutions.

Study Design: Financial navigators at 4 hospitals were trained through The NaVectis Group, an organization that provides training to healthcare staff to increase patient access to care and assist with OOP expenses.

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Mechanisms that maintain cancer stem cells are crucial to tumour progression. The ID2 protein supports cancer hallmarks including the cancer stem cell state. HIFα transcription factors, most notably HIF2α (also known as EPAS1), are expressed in and required for maintenance of cancer stem cells (CSCs).

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Background: Immigration from Ethiopia to Israel started about 30 years ago. We aimed to compare birth outcomes between Israeli women of Ethiopian origin and Israeli-born, non-Ethiopian women. We hypothesized a higher frequency of adverse birth outcomes among Ethiopian women and a trend of improvement among those who were raised in Israel since early childhood.

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Background: Little is known of the outcome of pregnant patients with previously diagnosed dilated cardiomyopathy. These patients are usually firmly advised against continuation of the pregnancy.

Objectives: To examine the usefulness of serial echocardiographic follow-up and plasma N-terminal pro-B type natriuretic peptide levels in the management of pregnant women with preexisting DCM.

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We performed a metaanalysis of publications comparing the efficacy and safety of cervical ripening and labor induction by Foley catheter balloon (FCB) vs locally applied prostaglandins (LAPG) in the third trimester of pregnancy. Twenty-seven randomized controlled trials (1966-2008; 3532 participants) were selected from MEDLINE, EMBASE, and CENTRAL searches. There was no significant difference between FCB and LAPG in cesarean delivery rates.

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Upper-arm weakness (paresis) or paralysis in the newborn (Erb's palsy) usually indicates peripheral-nerve damage to the brachial plexus. Its location lateral to the lower cervical spine (C5-T1) renders it susceptible to injury by pressure or traction during pregnancy, labor or delivery. The Medical Risk Management (MRM), a "Madanes" group company, routinely receives adverse events reports from medical centers covered by its medical malpractice insurance.

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A series of arylphthalazine derivatives were synthesized and evaluated as antagonists of VEGF receptor II (VEGFR-2). IM-094482 57, which was prepared in two steps from commercially available starting materials, was found to be a potent inhibitor of VEGFR-2 in enzymatic, cellular and mitogenic assays (comparable activity to ZD-6474). Additionally, 57 inhibited the related receptor, VEGF receptor I (VEGFR-1), and showed excellent exposure when dosed orally to female CD-1 mice.

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We have discovered novel inhibitors of VEGFR-2 kinase with low nanomolar potency in both enzymatic and cell-based assays. Active series are heteroaryl-ketone compounds containing a central aromatic ring with either an indazolyl or indolyl keto group in the ortho orientation to the benzylic amine group (Fig. 1).

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Objective: To present prenatal findings and maternal and neonatal outcomes following second- and early third-trimester spontaneous antepartum uterine rupture events in our institute.

Method: Charts of patients with full-thickness second- or early third-trimester symptomatic uterine ruptures locally treated between 1984 and 2007 were evaluated.

Results: There were seven events involving six women, all requiring emergency laparotomy, and cesarean section (CS).

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Objective: This manuscript discusses the clinical presentation, diagnosis, pathophysiology and possible etiologies of prenatal thrombosis of the inferior vena cava and renal veins.

Methods: Eleven cases were identified through a Medline search of the English literature. These cases were reviewed, together with a recent case that was treated in our medical center.

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Background: Ureaplasma urealyticum is the most common pathogen cultured from the amniotic cavity of women with preterm labor and intact membranes. However, experience with antibiotic eradication of the pathogen in this setting is limited.

Case: We report a case of U.

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Background: The Israeli Ministry of Health reported an increased rate of twin pregnancies among all cases locally diagnosed as having open neural tube defects. The current study aimed to evaluate whether the etiology of this phenomenon could be attributed either to the twinning or to the mode of conception.

Methods: Women admitted to our hospital between January 1997 and July 2004 for termination of pregnancy because of severe fetal abnormality enrolled into this retrospective case series study.

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A novel class of 4-arylamino-phthalazin-1-yl-benzamides is described as inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). Several compounds display potent VEGFR-2 inhibitory activity with an IC50 as low as 0.078 microM in an HTRF enzymatic assay.

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Fibrinogen abnormalities have been implicated in many adverse pregnancy outcomes, mainly spontaneous abortion, placental abruption, and postpartum hemorrhage. Two new cases of congenital hypofibrinogenemia in pregnancy are reported detailing their obstetric course and management. The relevant obstetric and hematologic literature is reviewed, including previous case reports and studies concerning the mechanisms of pregnancy complications.

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Purpose: The unintentional and unrecognized cannulation of an extradural vein is a potentially serious complication of an epidural anesthetic. The present study was undertaken to assess the incidence of blood vessel puncture related to epidural catheterization in three different body positions, in a cohort of morbidly obese parturients, following the completion of a similar study published in 2001 from which such parturients were excluded.

Methods: The study was conducted in 450 (three groups of 150) morbidly obese, obstetric patients undergoing continuous epidural analgesia during labour.

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Objective: This case report describes a rare clinical presentation of chorioangioma diagnosed prenatally because of raised-maternal serum (MS) alpha-fetoprotein.

Methods: A thirty-year-old woman gravida 2, para 1 was referred to the ultrasound unit at 18 weeks of gestation because of abnormal MS triple-test results. This included AFP level of 14.

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The p53 tumor suppressor gene was found to play a role in the differentiation of several tissue types. We report here that p53-dependent apoptosis plays a role in the final stages of physiological differentiation of normoblasts, resulting in nuclear condensation and expulsion without cell death. Blood samples of healthy newborns, cord blood as well as bone marrow, were analysed for apoptosis by TUNEL and p53 expression by immunostaining.

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Objective: To study the association between midtrimester triple-test levels and renal function in pregnant women with chronic hypertension.

Methods: Forty-three patients with chronic hypertension for whom renal function was evaluated by the creatinine clearance test between 14- and 20-weeks gestation were studied. Midtrimester triple-test values obtained as part of Down screening program were correlated with renal function.

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Objective: To find patterns characteristic of maternal heart rates recorded by an electronic fetal monitor and compare them with concomitant fetal heart rate (FHR) patterns.

Methods: Maternal heart rates and FHRs during active labor and delivery were simultaneously recorded in 26 parturients with singleton pregnancies in vertex presentation. The FHRs were obtained by an external ultrasound transducer or via a spiral scalp electrode and maternal heart rates by a triple-wire cable with electrocardiographic electrodes attached to the chest.

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