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Nadège Bossuet-Greif, Julien Vignard, Frédéric Taieb, Gladys Mirey, Damien Dubois, Claude Petit, Eric Oswald, Jean-Philippe Nougayrède
Colibactins are hybrid polyketide-nonribosomal peptides produced by Escherichia coli , Klebsiella pneumoniae , and other Enterobacteriaceae harboring the pks genomic island. These genotoxic metabolites are produced by pks -encoded peptide-polyketide synthases as inactive prodrugs called precolibactins, which are then converted to colibactins by deacylation for DNA-damaging effects. Colibactins are bona fide virulence factors and are suspected of promoting colorectal carcinogenesis when produced by intestinal E...
March 20, 2018: MBio
Salomon Y Cohen, Alexandra Miere, Sylvia Nghiem-Buffet, Franck Fajnkuchen, Eric H Souied, Sarah Mrejen
A review of the literature from 2014 to 2016 was conducted, focusing on the results of optical coherence tomography angiography in different chorioretinal diseases. In only 3 years, optical coherence tomography angiography has been shown to be an effective tool for diagnosing choroidal neovascularization complicating age-related macular degeneration, pathologic myopia, and inflammatory conditions. The technique has sometimes been considered superior to conventional multimodal imaging, for example, in choroidal neovascularization associated with chronic central serous chorioretinopathy or multifocal choroiditis...
March 1, 2018: European Journal of Ophthalmology
Li-Yun Fann, Ying Chen, Da-Chen Chu, Shao-Ju Weng, Heng-Cheng Chu, Alexander T H Wu, Jiann-Fong Lee, Ahmed Atef Ahmed Ali, Tsung-Chih Chen, Hsu-Shan Huang, Kuo-Hsing Ma
The small-molecule naphtha [2,3-f]quinoxaline-7,12-dione (NSC745887) can effectively inhibit the proliferation of various cancers by trapping DNA-topoisomerase cleavage. The aim of this study was to elucidate cellular responses of NSC745887 in human glioblastoma multiforme (GBM, U118MG and U87MG cells) and investigate the underlying molecular mechanisms. NSC745887 reduced the cell survival rate and increased the sub-G1 population in dose- and time-dependent manners in GBM cells. Moreover, NSC745887 increased expression of γH2AX and caused DNA fragmentation leading to DNA damage...
February 23, 2018: Oncotarget
Patrícia Leitão, André Carvalho, Conceição Guerra, José Gonçalves, Isabel Ramos
Hereditary hemorrhagic telangiectasia or Osler-Weber-Rendu syndrome is a rare autosomal dominant vascular disorder characterized by epistaxis, mucocutaneous telangiectasias, and arteriovenous malformations affecting various organs and systems. The liver is a commonly involved organ (74% of patients with hereditary hemorrhagic telangiectasia), although symptomatic liver disease is quite infrequent. In symptomatic cases, clinical manifestations relate most commonly to the predominant type of vascular shunting present (arteriovenous, arterioportal, or portovenous)...
February 2018: Radiology Case Reports
Marcelo D Vilela, Uedson Tazinaffo
Various mixed associations between arteriovenous malformations, cavernous malformations, developmental venous anomalies and capillary telangiectasias have been described and a common pathophysiological event has been suggested to be present, although yet to be elucidated. We depict herein the imaging features of a patient who presented with a spontaneous cerebellar hemorrhage, in whom radiological studies demonstrated a pontine telangiectasia, a brainstem/cerebellar developmental venous anomaly and a cerebellar proliferative angiopathy...
March 13, 2018: World Neurosurgery
Justin Stebbing, Kalpit Shah, Lei Cheng Lit, Teresa Gagliano, Angeliki Ditsiou, Tingting Wang, Franz Wendler, Thomas Simon, Krisztina Sára Szabó, Timothy O'Hanlon, Michael Dean, April Camilla Roslani, Swee Hung Cheah, Soo-Chin Lee, Georgios Giamas
Lemur tyrosine kinase 3 (LMTK3) is an oncogenic kinase that is involved in different types of cancer (breast, lung, gastric, colorectal) and biological processes including proliferation, invasion, migration, chromatin remodeling as well as innate and acquired endocrine resistance. However, the role of LMTK3 in response to cytotoxic chemotherapy has not been investigated thus far. Using both 2D and 3D tissue culture models, we found that overexpression of LMTK3 decreased the sensitivity of breast cancer cell lines to cytotoxic (doxorubicin) treatment...
March 15, 2018: Oncogene
Lauren Marissa Weber, Jamie McDonald, Kevin Whitehead
AIM: To explore the association between vitamin D levels and mild versus severe epistaxis, as well as the overall epistaxis severity score (ESS) in patients with hereditary hemorrhagic telangiectasia. PATIENTS & METHODS: A retrospective chart review of 198 patients was performed to explore the relationship between vitamin D levels and the ESS. Vitamin D levels were also compared with those with mild epistaxis to those with severe epistaxis. RESULTS: A significant difference was found between patient's vitamin D levels and their associated ESS and duration of epistaxis...
March 14, 2018: Biomarkers in Medicine
Tatsuo Miyamoto, Silvia Natsuko Akutsu, Hiroshi Tauchi, Yoshiki Kudo, Satoshi Tashiro, Takashi Yamamoto, Shinya Matsuura
DNA double-strand breaks (DSBs) induced by ionizing radiation (IR) are the initial and critical step in major alteration of genetic information and cell death. To prevent deleterious effects, DNA repair systems recognize and re-join DNA DSBs in human cells. It has been suggested that there are individual differences in radiosensitivity within human populations, and that variations in DNA repair genes might contribute to this heterogeneity. Because confounding factors, including age, gender, smoking, and diverse genetic backgrounds within human populations, also influence the cellular radiosensitivity, to accurately measure the effect of candidate genetic variations on radiosensitivity, it is necessary to use human cultured cells with a uniform genetic background...
March 8, 2018: Journal of Radiation Research
Dehong Huang, Lei Jin, Zhengkang Li, Ji Wu, Ni Zhang, Dianrong Zhou, Xiaorong Ni, Tieying Hou
Hepatoblastoma (HB) is the most common malignant liver tumor in children. DNA and DNA-associated processes are one of the most important targets of chemotherapeutic agents. Isoorientin (Iso), a natural flavonoid compound, can be extracted from several plant species. The effects of Iso and its molecular mechanisms on hepatic malignancies remain unclear. Herein, the anti-tumor effects of Iso in HB and its underlying mechanisms were explored. We found that Iso significantly inhibited the proliferation of HB cells both in vitro and in vivo...
March 7, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Diana A Olszewska, Terri McVeigh, Emer M Fallon, Gregory M Pastores, Tim Lynch
Genetics is the backbone of Neurology, where a number of disorders have a genetic aetiology and are complex, requiring a dedicated Neurogenetics clinic. Genetics in the Republic of Ireland is under-resourced, with the lowest number of consultants per million of population in Europe. In November 2014, we established the monthly adult Neurogenetics clinic in Ireland, staffed by 2 consultants and 2 registrars from each speciality. We see patients with complex rare neurological conditions that may potentially have an underlying genetic basis, in the presence or absence of a family history...
March 9, 2018: Irish Journal of Medical Science
Z X Yu, L Q Zhong, H M Song, C Y Wang, W Wang, J Li, M S Ma
Objective: To summarize the clinical characteristics and treatment efficacy of the first reported case of a Chinese boy with stimulator of interferon genes (STING) associated vasculopathy with onset in infancy (SAVI). Methods: Sanger sequencing of the gene TMEM173 was performed based on systemic evaluation and clinical analysis of a highly suspected SAVI child admitted to Peking Union Medical College Hospital. A literature search (search terms included 'STING''SAVI''autoinflammatory diseases' and 'interferonopathy') was conducted using Chinese literature database, EMBASE and PubMed to include recently published SAVI studies (searched from January 2010 to December 2017)...
March 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Danyela Valero-Rubio, Karen Marcela Jiménez, Dora Janeth Fonseca, César Payán-Gomez, Paul Laissue
Fucosidosis is a rare lysosomal storage disease which has been classified into two subtypes, depending on the severity of clinical signs and symptoms. Fucosidosis patients' skin abnormalities include angiokeratoma corporis diffusum, widespread telangiectasia, thick skin, hyperhidrosis and hypohidrosis, acrocyanosis and distal transverse nail bands. It has been described that >50% of fucosidosis patients have angiokeratoma. At molecular level, fucosidosis is caused by lysosomal alpha-L-fucosidase (FUCA1) gene mutations...
March 8, 2018: Experimental Dermatology
Xavier Verhelst, Anja Geerts, Hans Van Vlierberghe, Peter Smeets, Clarisse Lecluyse
We report the case of a young woman with hereditary hemorrhagic telangiectasia (HHT) with severe liver involvement and pulmonary shunting. The medical imaging in this patient illustrates the severe shunting that can occur in these patients who often are asymptomatic. By showing this case, we want to highlight the role of liver transplantation in HHT with hepatic involvement.
January 2018: Case Reports in Gastroenterology
Yusuke Yamamoto, Kohkichi Hosoda, Taichiro Imahori, Jun Tanaka, Kazuya Matsuo, Tomoaki Nakai, Yasuhiro Irino, Masakazu Shinohara, Naoko Sato, Takashi Sasayama, Kazuhiro Tanaka, Hiroaki Nagashima, Masaaki Kohta, Eiji Kohmura
Molecular mechanism underlying ischemic stroke remains poorly understood. We previously reported glucose 6-phosphate dehydrogenase (G6PD) activity in pentose phosphate pathway (PPP) is activated via heat shock protein 27 (HSP27) phosphorylation at serine 85 (S85) by ataxia telangiectasia mutated (ATM) kinase during cerebral ischemia. This mechanism seems to be endogenous antioxidative system. To determine whether this system also works during reperfusion, we performed comparative metabolic analysis of reperfusion effect on metabolism in rat cortex using middle cerebral artery occlusion (MCAO)...
March 3, 2018: Brain Research
Jingli Guo, WenYi Tang, Xiaofeng Ye, Haixiang Wu, Gezhi Xu, Wei Liu, Yongjin Zhang
BACKGROUND: To evaluate the structural changes associated with visual acuity (VA) in patients with idiopathic macular telangiectasia (MT) type 1 using multimodal imaging modalities. METHODS: A retrospective study of 14 patients with MT type 1 and of 10 eyes from 10 healthy individuals as age-matched controls was conducted. The medical records of patients who had undergone colour fundus photography, spectral domain optical coherence tomography (OCT), fluorescein angiography and OCT angiography were reviewed...
March 5, 2018: BMC Ophthalmology
Britta Weigelt, Rui Bi, Rahul Kumar, Pedro Blecua, Diana L Mandelker, Felipe C Geyer, Fresia Pareja, Paul A James, Fergus J Couch, Diana M Eccles, Fiona Blows, Paul Pharoah, Anqi Li, Pier Selenica, Raymond S Lim, Gowtham Jayakumaran, Nic Waddell, Ronglai Shen, Larry Norton, Hannah Y Wen, Simon N Powell, Nadeem Riaz, Mark E Robson, Jorge S Reis-Filho, Georgia Chenevix-Trench
Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs from ATM germline mutation carriers by whole-exome and targeted sequencing. ATM-associated BCs were consistently hormone receptor positive and largely displayed minimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity of mutational signature 3 associated with defective homologous recombination DNA (HRD) repair...
February 28, 2018: Journal of the National Cancer Institute
Xue-Ling Mei, Li Wang
Intense pulsed light (IPL) is effective for the treatment of lentigines, telangiectasia, and generalized erythema, but is less effective in the removal of skin wrinkles. Fractional laser is effective on skin wrinkles and textural irregularities, but can induce postinflammatory hyperpigmentation (PIH), especially in Asians. This study evaluated the safety and efficacy of ablative fractional laser (AFL) in combination with IPL in the treatment of photoaging skin in Asians.This study included 28 Chinese women with Fitzpatrick skin type III and IV...
January 2018: Medicine (Baltimore)
Abdulrahman AlDarrab, Yasser H Al-Faky, Ahmed Mousa, Adel H Alsuhaibani
PURPOSE: To study the effect of trachoma on meibomian glands using infrared meibography and to correlate the results with tear film parameters. METHODS: This is a prospective cohort study in which 86 eyes of healthy volunteers and 90 eyes with trachoma were included. Clinical assessment was performed including the following: slit-lamp examination looking for signs of sequelae of trachoma, tear breakup time (TBUT), superficial punctate keratopathy (SPK), Schirmer II test (with anesthesia), and meibum score...
April 2018: Cornea
Mohammed D Saleem, Jonathan K Wilkin
Erythematotelangiectatic rosacea is the most prevalent rosacea subtype. Multiple dermatologic conditions may mimic erythematotelangiectatic rosacea. The authors review a comprehensive approach to evaluating subjects with a suspected diagnosis of erythematotelangiectatic rosacea and discuss findings that may warrant further investigation. Differential diagnoses can be narrowed based on the presence of characteristics such as transient erythema, nontransient erythema, and telangiectasias. A thorough history and physical examination are critical in ruling out conditions such as dermatomyositis, lupus erythematosus, atopic dermatitis, and seborrheic dermatitis...
April 2018: Dermatologic Clinics
V M M Vorselaars, S Velthuis, M P Huitema, A E Hosman, C J J Westermann, R J Snijder, J J Mager, M C Post
AIM: Transthoracic contrast echocardiography (TTCE) is recommended for screening of pulmonary arteriovenous malformations (PAVMs) in hereditary haemorrhagic telangiectasia. Shunt quantification is used to find treatable PAVMs. So far, there has been no study investigating the reproducibility of this diagnostic test. Therefore, this study aimed to describe inter-observer and inter-injection variability of TTCE. METHODS: We conducted a prospective single centre study...
March 1, 2018: Netherlands Heart Journal
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