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Wan-Angkan Poolsri, Phornpun Phokrai, Somrudee Suwankulanan, Narinthorn Phakdeeto, Pattamaphorn Phunsomboon, Dumrongsak Pekthong, Lysiane Richert, Sutatip Pongcharoen, Piyarat Srisawang
Increased expression levels of both mitochondrial citrate transporter (CTP) and plasma membrane citrate transporter (PMCT) proteins have been found in various cancers. The transported citrates by these two transporter proteins provide acetyl-CoA precursors for the de novo lipogenesis (DNL) pathway to support a high rate of cancer cell viability and development. Inhibition of the DNL pathway promotes cancer cell apoptosis without apparent cytotoxic to normal cells, leading to the representation of selective and powerful targets for cancer therapy...
2018: BioMed Research International
Peter A Nigrovic, Timothy Beukelman, George Tomlinson, Brian M Feldman, Laura E Schanberg, Yukiko Kimura
BACKGROUND: Systemic juvenile idiopathic arthritis is a rare febrile arthritis of childhood characterized by a potentially severe course, including prolonged glucocorticoid exposure, growth failure, destructive arthritis, and life-threatening macrophage activation syndrome. Early cytokine-blocking biologic therapy may improve long-term outcomes, although some systemic juvenile idiopathic arthritis patients respond well to non-biologic treatment, leaving optimal management undefined. Consequently, treatment of new-onset systemic juvenile idiopathic arthritis by expert clinicians varies widely...
March 1, 2018: Clinical Trials: Journal of the Society for Clinical Trials
Baek Gyu Jun, Woong Cheul Lee, Jae Young Jang, Soung Won Jeong, Young Don Kim, Gab Jin Cheon, Yun Nah Lee, Sang Gyune Kim, Young Seok Kim, Young Sin Cho, Sae Hwan Lee, Hong Soo Kim
BACKGROUND: Spontaneous bacterial peritonitis (SBP) is one of the severe complications of liver cirrhosis. Early detection of high-risk patients is essential for prognostic improvement. The aim of this study is to investigate the predictive factors related to in-hospital mortality in patients with SBP. METHODS: This was a retrospective study of 233 SBP patients (181 males, 52 females) who were admitted to four tertiary referral hospitals between August 2002 and February 2013...
March 19, 2018: Journal of Korean Medical Science
A Bar-Ilan, T Livnat, M Hoffmann, L Binder, M Zakar, R Guy, Y Felikman, L Moschcovich, B Shenkman, D Monroe, O Hershkovitz, G Kenet, G Hart
INTRODUCTION: Recombinant FVIIa (rFVIIa) is an effective treatment for haemophilia through frequent administration. However, the short half-life of rFVIIa decreases its prophylactic ability to reduce bleeding. Carboxy-terminal peptide (CTP)-modified FVIIa (MOD-5014) is a long-acting rFVIIa developed for on-demand treatment of haemophilia using either an intravenous or subcutaneous injection with the aim of less frequent administrations, as well as for prophylactic use. AIM: The comprehensive evaluation of the activity MOD-5014 vs commercially available rhFVIIa, as well as their interaction with cofactors and inhibitors...
March 14, 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
Feina Shi, Zhicai Chen, Xiaoxian Gong, Meixia Zhang, David S Liebeskind, Min Lou
OBJECTIVE: To investigate the value of multi-segment clot (MSC) sign on dynamic CT angiography (CTA) in predicting recanalisation and outcome after reperfusion therapy in acute ischaemic stroke (AIS) with large artery occlusion (LAO). METHODS: We retrospectively reviewed data of anterior circulation LAO patients from a prospectively collected database for consecutive AIS patients who underwent perfusion CT (CTP) before treatment. MSC sign was defined as the presence of multiple segments on dynamic CTA derived from CTP data...
March 13, 2018: European Radiology
Tatsuru Yamada, Shoji Fujiwara, Kyohhei Fujita, Yuji Tsuchido, Takeshi Hashimoto, Takashi Hayashita
The construction of supramolecular recognition systems based on specific host-guest interactions has been studied in order to design selective chemical sensors. In this study, guest-responsive receptors for ATP have been designed with cyclodextrins (CyDs) as a basic prototype of the turn-on type fluorescent indicator. We synthesized dipicolylamine (DPA)-modified CyD-Cu2+ complexes ( Cu·1 α , Cu·1 β , and Cu·1 γ ), and evaluated their recognition capabilities toward phosphoric acid derivatives in water...
March 12, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Recep Sade, Mecit Kantarci, Berhan Genc, Hayri Ogul, Betul Gundogdu, Omer Yilmaz
Objective: Alveolar echinococcosis (AE) is a rare life-threatening parasitic infection. Computed tomography perfusion (CTP) imaging has the potential to provide both quantitative and qualitative information about the tissue perfusion characteristics. The purpose of this study was the examination of the characteristic features and feasibility of CTP in AE liver lesions. Material and Methods: CTP scanning was performed in 25 patients who had a total of 35 lesions identified as AE of the liver...
February 2018: Eurasian Journal of Medicine
Tomohide Yoshie, Toshihiro Ueda, Tatsuro Takada, Shinji Nogoshi, Fumio Miyashita, Satoshi Takaishi, Takayuki Fukano, Daiki Tokuura, Yasuhiro Hasegawa
BACKGROUND: Faster time to recanalization leads to better clinical outcomes in patients treated with endovascular thrombectomy. Whether the association between time to recanalization and clinical outcomes depends on cerebral blood volume (CBV) obtained from pretreatment computed tomography (CT) perfusion (CTP) imaging was investigated. METHODS: In consecutive patients with acute ischemic stroke who achieved recanalization by endovascular thrombectomy for intracranial internal carotid artery or M1 occlusion, the effects on clinical outcome of time to recanalization and the relative CBV value (rCBV) assessed by pretreatment CTP were evaluated...
March 7, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Mohsen Ramezanpour, Jaeyong Lee, Svetla G Taneva, D Peter Tieleman, Rosemary B Cornell
The activity of CTP:phosphocholine cytidylyltransferase (CCT), a key enzyme in phosphatidylcholine synthesis, is regulated by reversible interactions of a lipid-inducible amphipathic helix (domain M) with membrane phospholipids.  When dissociated from membranes a portion of the M domain functions as an auto-inhibitory (AI) element to suppress catalysis.  The AI helix from each subunit binds to a pair of α-helices (αE) that extend from the base of the catalytic dimer to create a four-helix bundle. The bound AI helices make intimate contact with loop L2, housing a key catalytic residue, Lys-122...
March 8, 2018: Journal of Biological Chemistry
Reem Waziry, Asmaa Gomaa, Imam Waked, Gregory J Dore
BACKGROUND AND STUDY AIMS: In this study we assessed rates and determinants of survival in people with untreated chronic HCV infection and hepatocellular carcinoma (HCC) in an Egyptian liver clinic setting. PATIENTS AND METHODS: This is a prospective cohort study of patients diagnosed with HCV-related HCC and undergoing HCC management at a national liver centre in Egypt in 2013-2014 and with a follow-up through 2016. RESULTS: A total of 345 patients diagnosed with HCV-related liver cirrhosis complicated by HCC were included...
March 2, 2018: Arab Journal of Gastroenterology: the Official Publication of the Pan-Arab Association of Gastroenterology
Gregory D McCluskey, Stephen L Bearne
While enzyme activity is often regulated by a combination of substrate/effector availability and quaternary structure, many cytosolic enzymes may be further regulated through oligomerization into filaments. CTP synthase (CTPS) forms such filaments - a process that is promoted by the product CTP. The CTP analogue and active chemotherapeutic metabolite gemcitabine-5'-triphosphate (dF-dCTP) is a potent inhibitor of CTPS; however, its effect on the enzyme's ability to form filaments is unknown. Alongside electron microscopy studies, dynamic light scattering showed that dF-dCTP induces Escherichia coli CTPS (EcCTPS) to form filaments in solution with lengths ≥30 nm in the presence of CTP or dF-dCTP...
March 1, 2018: Journal of Molecular Biology
Longting Lin, Andrew Bivard, Timothy Kleinig, Neil J Spratt, Christopher R Levi, Qing Yang, Mark W Parsons
BACKGROUND AND PURPOSE: This study aimed to assess how the ischemic core measured by perfusion computed tomography (CTP) was affected by the delay and dispersion effect. METHODS: Ischemic stroke patients having CTP performed within 6 hours of onset were included. The CTP data were processed twice, generating standard cerebral blood flow (sCBF) and delay- and dispersion-corrected CBF (ddCBF), respectively. Ischemic core measured by the sCBF and ddCBF was then compared at the relative threshold <30% of normal tissue...
March 2, 2018: Stroke; a Journal of Cerebral Circulation
Bharath Yarlagadda, Mohit K Turagam, Tawseef Dar, Pragna Jangam, Vaishnavi Veerapaneni, Donita Atkins, Sudharani Bommana, Paul Friedman, Abhishek J Deshmukh, Rahul Doshi, Vivek Y Reddy, Srinivas R Dukkipati, Andrea Natale, Dhanunjaya Lakkireddy
BACKGROUND: Atrioventricular node (AV) ablation and permanent pacing is an established strategy for rate control in the management of symptomatic atrial fibrillation (AF). Leadless pacemakers (LP) can overcome some of the short-term and long-term limitations of conventional transvenous pacemakers (CTP). OBJECTIVES: Compare the feasibility and safety of LP vs single chamber CTP in AF patients undergoing AVN ablation. METHODS: We conducted a multicenter, observational study of patients undergoing AVN ablation and pacemaker implantation (LP vs...
February 26, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Kazuhiro Murayama, Shigetaka Suzuki, Ryo Matsukiyo, Akinori Takenaka, Motoharu Hayakawa, Takashi Tsutsumi, Kenji Fujii, Kazuhiro Katada, Hiroshi Toyama
Noncontrast computed tomography (NCCT) has been used for the detection of early ischemic change (EIC); however, correct interpretation of NCCT findings requires much clinical experience. This study aimed to assess the accuracy of time maximum intensity projection computed tomography technique (tMIP), which reflects the maximum value for the time phase direction from the dynamic volume data for each projected plane, for detection of EIC, against that of NCCT.Retrospective review of NCCT, cerebral blood volume in CT perfusion (CTP-CBV), and tMIP of 186 lesions from 280 regions evaluated by Alberta Stroke Program Early CT Score (ASPECTS) in 14 patients with acute middle cerebral artery stroke who had undergone whole-brain CTP using 320-row area detector CT was performed...
March 2018: Medicine (Baltimore)
Liam F Fitzsimmons, Lin Liu, Ju-Sim Kim, Jessica Jones-Carson, Andrés Vázquez-Torres
The adaptations that protect pathogenic microorganisms against the cytotoxicity of nitric oxide (NO) engendered in the immune response are incompletely understood. We show here that salmonellae experiencing nitrosative stress suffer dramatic losses of the nucleoside triphosphates ATP, GTP, CTP, and UTP while simultaneously generating a massive burst of the alarmone nucleotide guanosine tetraphosphate. RelA proteins associated with ribosomes overwhelmingly synthesize guanosine tetraphosphate in response to NO as a feedback mechanism to transient branched-chain amino acid auxotrophies...
February 27, 2018: MBio
Jayendra Chunduru, Thomas P West
Regulation of pyrimidine biosynthesis by pyrimidines in the emerging, opportunistic human pathogen <i>Pseudomonas monteilii</i> ATCC 700476 was evident. When wild type cells were grown on succinate in the presence of uracil or orotic acid, all five pyrimidine biosynthetic enzyme activities were depressed while three enzyme activities decreased in glucose-grown cells supplemented with uracil or orotic acid compared to unsupplemented cells. Pyrimidine limitation of succinate-grown or glucose-grown pyrimidine auxotrophic cells lacking orotate phosphoribosyltransferase activity resulted in more than a doubling of the pyrimidine biosynthetic enzyme activities relative to their activities in uracil-grown cells...
February 27, 2018: Canadian Journal of Microbiology
Matthew A Baker, Chia-Hua Tsai, Kevin Joseph Taaffe Noonan
Chain-growth polymerization of aromatic building blocks (termed catalyst-transfer polycondensation or CTP) has emerged as a powerful method for the controlled synthesis of conjugated polymers. CTP affords semiconducting materials with predictable molecular weights, relatively narrow molar mass distributions and tailored backbone compositions (e.g. blocks, gradients, stars). Homogeneous catalysis utilizing transition metals has played a critical role in the rise of this field and this mini-review is designed to highlight some of the catalysts employed for these polycondensations...
February 27, 2018: Chemistry: a European Journal
Meixian Huang, Takeshi Inukai, Kunio Miyake, Yoichi Tanaka, Keiko Kagami, Masako Abe, Hiroaki Goto, Masayoshi Minegishi, Shotaro Iwamoto, Eiji Sugihara, Atsushi Watanabe, Shinpei Somazu, Tamao Shinohara, Hiroko Oshiro, Koshi Akahane, Kumiko Goi, Kanji Sugita
Cytosine arabinoside (Ara-C) is one of the key drugs for the treatment of acute myeloid leukemia. It is also used for consolidation therapy of acute lymphoblastic leukemia (ALL). Ara-C is a deoxyadenosine analog and is phosphorylated to form cytosine arabinoside triphosphate (Ara-CTP) as an active form. In the first step of the metabolic pathway, Ara-C is phosphorylated to Ara-CMP by deoxycytidine kinase (DCK). However, the current cumulative evidence in the association of the Ara-C sensitivity in ALL appears inconclusive...
February 23, 2018: Cancer Medicine
Andrew Bivard, Neil Spratt, Ferdinand Miteff, Christopher Levi, Mark William Parsons
Aim: The relative prognostic importance of modern imaging profiles compared with standard clinical characteristics is uncertain in acute stroke patients. In this study, we aimed to compare baseline multimodal CT imaging measures with known clinical predictors of patient outcome at 3 months [modified Rankin scale (mRS)]. Methods: We collected baseline, 24 h, and day 90 clinical and imaging data from acute ischemic stroke patients being assessed for thrombolytic therapy between 2010 and 2015 at a single center as part of a retrospective analysis...
2018: Frontiers in Neurology
Tae Hyung Kim, Dae Hoe Ku, Soon Ho Um, Han Ah Lee, Seung Woon Park, Jung Mi Chang, Sun Young Yim, Sang Jun Suh, Young Kul Jung, Yeon Seok Seo, Ji Hoon Kim, Hyung Joon Yim, Jong Eun Yeon, Kwan Soo Byun, Hyonggin Ahn
BACKGROUND AND AIM: We aimed to develop a more efficient prognostic model to predict 1-year mortality in patients with hepatitis B virus (HBV)-related decompensated cirrhosis beginning antiviral treatment. METHODS: Using Cox regression analysis, survival analyses were performed on 554 patients with decompensated cirrhosis who were followed up from the start of nucleos(t)ide analogue antiviral treatment. RESULTS: At baseline, ascites and hepatic encephalopathy were found in 78...
February 20, 2018: Journal of Gastroenterology and Hepatology
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