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[PMID]: 29524834
[Au] Autor:Gil-Ranedo J; Hernando E; Valle N; Riolobos L; Maroto B; Almendral JM
[Ad] Address:Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), Cantoblanco, 28049 Madrid, Spain.
[Ti] Title:Differential phosphorylation and n-terminal configuration of capsid subunits in parvovirus assembly and viral trafficking.
[So] Source:Virology;518:184-194, 2018 Mar 07.
[Is] ISSN:1096-0341
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The T1 parvovirus Minute Virus of Mice (MVM) was used to study the roles that phosphorylation and N-terminal domains (Nt) configuration of capsid subunits may play in icosahedral nuclear viruses assembly. In synchronous MVM infection, capsid subunits newly assembled as two types of cytoplasmic trimeric intermediates (3VP2, and 1VP1:2VP2) harbored a VP1 phosphorylation level fivefold higher than that of VP2, and hidden Nt. Upon nuclear translocation at S phase, VP1-Nt became exposed in the heterotrimer and subsequent subviral assembly intermediates. Empty capsid subunits showed a phosphorylation level restored to VP1:VP2 stoichiometry, and the Nt concealed in their interior. However ssDNA-filled virus maturing at S/G2 lacked VP1 phosphorylation and one major VP2 phosphopeptide, and exposed VP2-Nt. Endosomal VP2-Nt cleavage resulted in VP3 subunits devoid of any phospholabel, implying that incoming viral particles specifically harbor a low phosphorylation status. Phosphorylation provides a mechanistic coupling of parvovirus nuclear assembly to the cell cycle.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  2 / 1831466 MEDLINE  
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[PMID]: 29524832
[Au] Autor:Jonsson S; Oda H; Lundin E; Olsson J; Idahl A
[Ad] Address:Department of Clinical Science, Obstetrics and Gynecology, Umeå University, SE-901 87 Umeå, Sweden.
[Ti] Title:Chlamydia trachomatis, Chlamydial Heat Shock Protein 60 and Anti-Chlamydial Antibodies in Women with Epithelial Ovarian Tumors.
[So] Source:Transl Oncol;11(2):546-551, 2018 Mar 07.
[Is] ISSN:1936-5233
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: Chlamydia trachomatis (C. trachomatis) infection has been suggested to promote epithelial ovarian cancer (EOC) development. This study sought to explore the presence of C. trachomatis DNA and chlamydial heat shock protein 60 (chsp60) in ovarian tissue, as well as anti-chlamydial IgG antibodies in plasma, in relation to subtypes of EOC. METHODS: This cross-sectional cohort consisted of 69 women who underwent surgery due to suspected ovarian pathology. Ovarian tissue and corresponding blood samples were collected at the time of diagnosis. In ovarian tumor tissue, p53, p16, Ki67 and chsp60 were analyzed immunohistochemically, and PCR was used to detect C. trachomatis DNA. Plasma C. trachomatis IgG and cHSP60 IgG were analyzed with a commercial MIF-test and ELISA, respectively. RESULTS: Eight out of 69 women had C. trachomatis DNA in their ovarian tissue, all were invasive ovarian cancer cases (16.7% of invasive EOC). The prevalence of the chsp60 protein, C. trachomatis IgG and cHSP60 IgG in HGSC, compared to other ovarian tumors, was 56.0% vs. 37.2% P = .13, 15.4% vs. 9.3% P = .46 and 63.6% vs. 45.5% P = .33 respectively. None of the markers of C. trachomatis infection were associated with p53, p16 or Ki67. CONCLUSIONS: C. trachomatis was detected in invasive ovarian cancer, supporting a possible role in carcinogenesis of EOC. However, there were no statistically significant associations of chsp60 in ovarian tissue, or plasma anti-chlamydial IgG antibodies, with any of the subtypes of ovarian tumors.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29524828
[Au] Autor:Witt-Kehati D; Fridkin A; Alaluf MB; Zemel R; Shlomai A
[Ad] Address:Felsenstein Medical Research Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
[Ti] Title:Inhibition of pMAPK14 Overcomes Resistance to Sorafenib in Hepatoma Cells with Hepatitis B Virus.
[So] Source:Transl Oncol;11(2):511-517, 2018 Mar 07.
[Is] ISSN:1936-5233
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Hepatitis B virus (HBV) targets the liver and is a major driver for liver cancer. Clinical data suggest that HBV infection is associated with reduced response to treatment with the multi-kinase inhibitor sorafenib, the first available molecularly targeted anti-hepatocellular carcinoma (HCC) drug. Given that Raf is one of the major targets of sorafenib, we investigated the activation state of the Raf-Mek-Erk pathway in the presence of HBV and in response to sorafenib. Here we show that hepatoma cells with replicating HBV are less susceptible to sorafenib inhibitory effect as compared to cells in which HBV expression is suppressed. However, although HBV replication is associated with increased level of pErk, its blockade only modestly augments sorafenib effect. In contrast, the phosphorylated form of the pro-oncogenic Mitogen-Activated Protein Kinase 14 (pMAPK14), a protein kinase that was recently linked to sorafenib resistance, is induced in sorafenib-treated hepatoma cells in association with HBV X protein expression. Knocking down pMAPK14 results in augmentation of the therapeutic efficacy of sorafenib and largely alleviates resistance to sorafenib in the presence of HBV. Thus, this study suggests that HBV promotes HCC resistance to sorafenib. Combining pMAPK14 inhibitors with sorafenib may be beneficial in patients with HBV-associated HCC.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29524791
[Au] Autor:Noda-Nicolau NM; Polettini J; da Silva MG; Peltier MR; Menon R
[Ad] Address:Division of Maternal-Fetal Medicine and Perinatal Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United States; Department of Pathology, Botucatu Medical School, UNESP - Univ. Estadual Paulista, Botucatu, São Paulo, Brazil.
[Ti] Title:Polybacterial stimulation suggests discrete IL-6/IL-6R signaling in human fetal membranes: Potential implications on IL-6 bioactivity.
[So] Source:J Reprod Immunol;126:60-68, 2018 Mar 02.
[Is] ISSN:1872-7603
[Cp] Country of publication:Ireland
[La] Language:eng
[Ab] Abstract:The polybacterial invasion of the amniotic cavity and risk of preterm birth is often due to cervicovaginal bacteria such as genital mycoplasmas (Mycoplasma hominis and Ureaplasma urealyticum) and Gardnerella vaginalis. The most studied biomarker associated with preterm birth is interleukin-6 (IL-6), a pleiotropic cytokine that performs different functions based on classical or trans-signaling mechanisms. This study evaluated the changes in IL-6 and IL-6 function associated accessory molecules by human fetal membranes to determine the functional availability of IL-6 assessment in an in vitro model of polybacterial infection. Fetal membranes were treated with LPS or heat-inactivated genital mycoplasmas and G. vaginalis alone or in combination. IL-6 and its soluble receptors (sgp130, sIL-6R) were assessed in conditioned medium by immunoassays and membrane-bound receptors were evaluated in the tissue using immunohistochemistry and RT-PCR. Data from protein and gene expression were evaluated using linear mixed effects models. Data from immunohistochemistry were evaluated using one-way analysis of variance followed by the Tukey test. Genital mycoplasmas alone, or in combination, inhibited IL-6 trans-signaling with increased sgp130 production. G. vaginalis activated the classical IL-6 signaling pathway, as did LPS. Polybacterial treatment resulted in a balanced response with neither pathway being favored. The increase in IL-6 production by fetal membranes in response to infection is likely a non-specific innate response and not an indicator of a functional mediator of any labor-inducing pathways. This suggests that correlating the risk of adverse pregnancy outcomes and designing interventions based on IL-6 levels without considering soluble receptors may be an ineffective strategy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29524662
[Au] Autor:Schirmer A; Swan C; Hughes SJ; Vasilopoulos T; Oli M; Chaudhry S; Gravenstein N; Giordano C
[Ad] Address:Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL.
[Ti] Title:Break Scrub to Take That Phone Call?
[So] Source:J Am Coll Surg;, 2018 Mar 07.
[Is] ISSN:1879-1190
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: The American College of Surgeons reports that 60% of the hundreds of thousands of surgical site infections occurring annually are preventable. The practice of surgeons taking phone calls while remaining sterile in the operating field is often accomplished by interposing a sterile disposable towel between the phone and their glove. After completing the call, surgeons resume operating. The purpose of our study is to test the conceptual idea of whether bacteria transmit from an inanimate object, such as a telephone, to the gloves of a surgeon through a sterile disposable towel. STUDY DESIGN: GloGerm™, a UV light-enhanced particle powder sized to mimic bacteria, was placed on an inanimate surface and held with a sterile disposable OR towel covering a sterile surgical glove. The glove was then inspected for GloGerm™ using a UV light. Additionally, 18 operating room telephones were cultured and then held with a Sterile Disposable OR Towel (Medline Industries Inc., Northfield, IL) covering a sterile surgical glove. The surgical gloves were then cultured to determine if bacteria had transmitted from the telephone through the towel and onto the sterile glove. RESULTS: The GloGerm™ powder readily transmitted through the towel to the gloves. Median CFU on the cultured telephones for the 17 samples was 10, ranging from 1 to 35 CFUs. Of these 17 samples, 47% had transmission from the telephone to the glove, which was significantly greater than 0% (95% CI: 26%-69%, p < 0.001). CONCLUSIONS: Sterile disposable OR towels do not provide an effective barrier between bacteria present on operating room telephones and the otherwise sterile gloves of a surgeon.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  6 / 1831466 MEDLINE  
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[PMID]: 29524654
[Au] Autor:Aktories K; Papatheodorou P; Schwan C
[Ad] Address:Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Albertstr. 25, 79104 Freiburg, Germany; Centre for Biological Signalling Studies (BIOSS), University of Freiburg, 79104 Freiburg, Germany. Electronic address: klaus.aktories@pharmakol.uni-freiburg.de.
[Ti] Title:Binary Clostridium difficile toxin (CDT) - A virulence factor disturbing the cytoskeleton.
[So] Source:Anaerobe;, 2018 Mar 07.
[Is] ISSN:1095-8274
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Clostridium difficile infection causes antibiotics-associated diarrhea and pseudomembranous colitis. Major virulence factors of C. difficile are the Rho-glucosylating toxins TcdA and TcdB. In addition, many, so-called hypervirulent C. difficile strains produce the binary actin-ADP-ribosylating toxin CDT. CDT causes depolymerization of F-actin and rearrangement of the actin cytoskeleton. Thereby, many cellular functions, which depend on actin, are altered. CDT disturbs the dynamic balance between actin and microtubules in target cells. The toxin increases microtubule polymerization and induces the formation of microtubule-based protrusions at the plasma membrane of target cells. Moreover, CDT causes a redistribution of vesicles from the basolateral side to the apical side, where extracellular matrix proteins are released. These processes may increase the adherence of clostridia to target cells. Here, we review the effects of the action of CDT on the actin cytoskeleton and on the microtubule system.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  7 / 1831466 MEDLINE  
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[PMID]: 29524642
[Au] Autor:Mohd Ali MR; Mohd Safee AW; Ismail NH; Sapian RA; Hussin HM; Ismail N; Yean CY
[Ad] Address:Department of Medical Microbiology & Parasitology, School of Medical Science, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia; Secretariat National Institutes of Health (NIH), Ministry of Health Malaysia, c/o Institut Pengurusan Kesihatan, Jalan Rumah Sakit Bang
[Ti] Title:Development and validation of pan-Leptospira Taqman qPCR for the detection of Leptospira spp. in clinical specimens.
[So] Source:Mol Cell Probes;, 2018 Mar 07.
[Is] ISSN:1096-1194
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Early diagnosis of leptospirosis is important for ensuring better clinical management and achieving better outcomes. Currently, serological assays suffer from inconsistent performance and are less useful for early diagnosis of leptospirosis. As an alternative, qPCR is more sensitive, specific and able to detect the presence of leptospiral DNA during the acute phase of the infection. Meanwhile, most molecular assays do not detect the non-pathogenic group of Leptospira, even though these groups may also infect humans, although less frequently and less severely. METHODS: A set of primers and probe targeting rrs genes of 22 Leptospira spp. were designed and evaluated on 31 Leptospira isolates, 41 other organisms and 65 clinical samples from suspected patients. RESULTS: The developed assay was able to detect as low as 20 fg Leptospira DNA per reaction (equivalent to 4 copies) and showed high specificity against the tested leptospiral strains. No cross amplification was observed with the other organisms. During the evaluation of the confirmed clinical specimens, the developed assay was able to correctly identify all positive samples (n = 10/10). One amplification was observed in a negative sample (n = 1/55). The sequencing of the PCR product of the discordant sample revealed that the sequences were similar to those of L. interrogans and L. kirschneri. CONCLUSION: The findings suggest that the developed Taqman qPCR assay is sensitive, specific and has potential to be applied in a larger subsequent study.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29524641
[Au] Autor:Batinga MCA; de Lima JTR; Gregori F; Diniz JA; Muner K; Oliveira TMFS; Ferreira HL; Soares RM; Keid LB
[Ad] Address:Departamento de Medicina Veterinária Preventiva e Saúde Animal da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo, São Paulo, SP, Brazil.
[Ti] Title:Comparative application of IS711-based polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) for canine brucellosis diagnosis.
[So] Source:Mol Cell Probes;, 2018 Mar 07.
[Is] ISSN:1096-1194
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Canine brucellosis is caused by Brucella canis, a gram negative and facultative intracellular bacterium that is commonly associated with reproductive failures in dogs. The accurate diagnosis of the infection relies on the use of serological tests associated with blood culturing to guarantee sensitivity. The polymerase chain reaction (PCR) can replace the culturing procedure for the direct diagnosis of the infection because of its speed, high specificity and sensitivity values; however, it depends on some laboratory infrastructure to be conducted. The loop-mediated isothermal amplification (LAMP) may be an alternative method for DNA amplification in a shorter period, using simpler equipment, and with a lower cost. This study evaluated the potential of molecular tools based on PCR and LAMP using primers targeting the insertion sequence IS711 for Brucella detection in three groups of dogs (infected, non-infected and suspected of brucellosis), which were determined according to the results of blood culturing and clinical examination. The performance of the three diagnostic tests was also determined using McNemar test and Kappa coefficient. The proportion of positive samples detected by blood culturing, PCR and LAMP was respectively 31.57% (18/57), 33.34% (19/57), and 14.03% (8/57). The agreement between blood culturing and PCR was almost perfect, while the agreement of PCR and blood culturing compared to LAMP was fair. The diagnostic sensitivity of PCR and LAMP was respectively 100% (18/18) and 44.44% (8/18), while the diagnostic specificity of both tests was 100% (21/21). LAMP performance was not satisfactory for canine brucellosis diagnosis because of the low diagnostic sensitivity of the test. The IS711 based PCR, otherwise, showed high values of sensitivity and specificity, which makes it a good alternative for use for the rapid diagnosis of canine brucellosis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  9 / 1831466 MEDLINE  
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[PMID]: 29524618
[Au] Autor:Eedara BB; Rangnekar B; Doyle C; Cavallaro A; Das SC
[Ad] Address:School of Pharmacy, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand.
[Ti] Title:The influence of surface active L-leucine and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) in the improvement of aerosolization of pyrazinamide and moxifloxacin co-spray dried powders.
[So] Source:Int J Pharm;, 2018 Mar 07.
[Is] ISSN:1873-3476
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Pharmacotherapy of tuberculosis is potentially more efficient when delivered by the inhaled route than by the current oral and/or parenteral routes due to the higher concentration of drug reaching the primary region of infection in the lungs. This study investigated the influence of the amino acid L-leucine alone and in combination with the phospholipid, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), on the aerosolization behaviour of the anti-TB drugs, pyrazinamide and moxifloxacin HCl. Spray dried powders of pyrazinamide (P), moxifloxacin (M) alone and in combination with 10% L-leucine (PL and ML) and 10% DPPC (PLD and MLD) were produced. The particle sizes of all powders except P were in the inhalable size range (< 5 µm) but differ in their morphology in presence of the excipients. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed the migration of surface active L-leucine and DPPC onto the surface of the particles during the spray drying process. The aerosolization from a dry powder inhaler, Aerolizer , using a next generation impactor revealed fine particle fraction (FPF) values for P, PL and PLD of 18.7 ± 3.4%, 53.0 ± 3.2% and 74.5 ± 5.3% respectively while FPF values for M, ML and MLD were 55.6 ± 3.3%, 74.7 ± 4.7% and 74.1 ± 1.3% respectively. In conclusion, the differences in the aerosolization behaviours of the pyrazinamide and moxifloxacin spray dried powders with and without excipients was a combination of difference in the surface morphology and surface composition.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  10 / 1831466 MEDLINE  
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[PMID]: 29524615
[Au] Autor:Chauhan V; Goyal K; Singh MP
[Ad] Address:Department of Virology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, Punjab 160012, India.
[Ti] Title:Identification of broadly reactive epitopes targeting major glycoproteins of Herpes simplex virus (HSV) 1 and 2 - An immunoinformatics analysis.
[So] Source:Infect Genet Evol;, 2018 Mar 07.
[Is] ISSN:1567-7257
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Infections due to both HSV-1 and HSV-2 constitute an enormous health burden worldwide. Development of vaccine against herpes infections is a WHO supported public health priority. The viral glycoproteins have always been the major hotspots for vaccine designing. The present study was aimed to identify the conserved T and B cell epitopes in the major glycoproteins of both HSV-1 and HSV-2 via rigorous computational approaches. Identification of promiscuous T cell epitopes is of utmost importance in vaccine designing as such epitopes are capable of binding to several allelic forms of HLA and could generate effective immune response in the host. The criteria designed for identification of T and B cell epitopes was that it should be conserved in both HSV-1 and 2, promiscuous, have high affinity towards HLA alleles, should be located on the surface of glycoproteins and not be present in the glycosylation sites. This study led to the identification of 17 HLA Class II and 26 HLA Class I T cell epitopes, 9 linear and some conformational B cell epitopes. The identified T cell epitopes were further subjected to molecular docking analysis to analyze their binding patterns. Altogether we have identified 4 most promising regions in glycoproteins (2-gB, 1-gD, 1-gH) of HSV-1 and 2 which are promiscuous to HLA Class II alleles and have overlapping HLA Class I and B cell epitopes, which could be very useful in generating both arms of immune response in the host i.e. adaptive as well as humoral immunity. Further the authors propose the cross-validation of the identified epitopes in experimental settings for confirming their immunogenicity to support the present findings.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher


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