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  • 1
    Publication Date: 2018-04-28
    Description: This work evaluated the use of the positron emission tomography (PET)/computed tomography (CT) technique to assess the early therapeutic response and predict the prognosis of patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) who underwent apatinib therapy. Standardised uptake value (SUV), metabolic tumour volume (MTV) and total lesion glycolysis (TLG), derived from 18 F-FDG PET/CT and SUV from 68 Ga-NOTA-PRGD2 PET/CT were evaluated. Tumour response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Sixteen of 20 patients achieved partial response (PR) and four of 20 had stable disease (SD) after apatinib therapy. Six progression-free survival (PFS) events occurred. A strong correlation was observed between the best change in the sum of the longest diameters of target lesions (CT%) and 18 F-FDG PET/CT indices after the completion of the first treatment cycle (MTV% ( P = 0.0019), TLG% ( P = 0.0021) and SUVmax% ( P = 0.0443)). A significant difference in PFS was observed between patients with MTV% 〈–45% and ≥–45% ( P = 0.0019) and between patients with TLG% 〈–80% and ≥–80% ( P = 0.0065). Ten of 11 patients presented a decrease in SUVmax on 68 Ga-NOTA-PRGD2 PET/CT after two cycles of apatinib therapy and showed PR, whereas one patient presenting an increase in SUVmax only showed SD as the best response. When a cut-off value of the target/background ratio at –20% was used, two PFS curves showed a significant difference ( P = 0.0016). Hence, early assessment by 18 F-FDG and 68 Ga-NOTA-PRGD2 PET/CT was effective in the prediction and evaluation of RAIR-DTC treated with apatinib.
    Print ISSN: 1351-0088
    Electronic ISSN: 1479-6821
    Topics: Medicine
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  • 2
    Publication Date: 2018-05-09
    Description: Objective Functional gastrointestinal disorders (FGIDs) are diagnosed by the presence of a characteristic set of symptoms. However, the current criteria-based diagnostic approach is to some extent subjective and largely derived from observations in English-speaking Western patients. We aimed to identify latent symptom clusters in Asian patients with FGID. Design 1805 consecutive unselected patients with FGID who presented for primary or secondary care to 11 centres across Asia completed a cultural and linguistic adaptation of the Rome III Diagnostic Questionnaire that was translated to the local languages. Principal components factor analysis with varimax rotation was used to identify symptom clusters. Results Nine symptom clusters were identified, consisting of two oesophageal factors (F6: globus, odynophagia and dysphagia; F9: chest pain and heartburn), two gastroduodenal factors (F5: bloating, fullness, belching and flatulence; F8 regurgitation, nausea and vomiting), three bowel factors (F2: abdominal pain and diarrhoea; F3: meal-related bowel symptoms; F7: upper abdominal pain and constipation) and two anorectal factors (F1: anorectal pain and constipation; F4: diarrhoea, urgency and incontinence). Conclusion We found that the broad categorisation used both in clinical practice and in the Rome system, that is, broad anatomical divisions, and certain diagnoses with long historical records, that is, IBS with diarrhoea, and chronic constipation, are still valid in our Asian societies. In addition, we found a bowel symptom cluster with meal trigger and a gas cluster that suggests a different emphasis in our populations. Future studies to compare a non-Asian cohort and to match to putative pathophysiology will help to verify our findings.
    Keywords: Gut
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 3
    Publication Date: 2018-05-23
    Description: Recent studies revealed that acetylation is a widely used protein modification in prokaryotic organisms. The major protein acetylation acetyltransferase YfiQ and the sirtuin-like deacetylase CobB have been found to be involved in basic physiological processes, such as primary metabolism, chemotaxis, and stress responses, in Escherichia coli and Salmonella . However, little is known about protein acetylation modifications in Yersinia pestis , a lethal pathogen responsible for millions of human deaths in three worldwide pandemics. Here we found that Yp_0659 and Yp_1760 of Y. pestis encode the major protein acetylation acetyltransferase YfiQ and the sirtuin-like deacetylase CobB, respectively, which can acetylate and deacetylate PhoP enzymatically in vitro . Protein acetylation impairment in cobB and yfiQ mutants greatly decreased bacterial tolerance to cold, hot, high-salt, and acidic environments. Our comparative transcriptomic data revealed that the strongly decreased tolerance to stress stimuli was probably related to downregulation of the genes encoding the heat shock proteins (HtpG, HslV, HslR, and IbpA), cold shock proteins (CspC and CspA1), and acid resistance proteins (HdeB and AdiA). We found that the reversible acetylation mediated by CobB and YfiQ conferred attenuation of virulence, probably partially due to the decreased expression of the psaABCDEF operon, which encodes Psa fimbriae that play a key role in virulence of Y. pestis . This is the first report, to our knowledge, on the roles of protein acetylation modification in stress responses, biofilm formation, and virulence of Y. pestis .
    Print ISSN: 0019-9567
    Electronic ISSN: 1098-5522
    Topics: Medicine
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  • 4
    Publication Date: 2018-02-27
    Description: Pyrrolizidine alkaloids (PAs) are extensively synthesized by plants, are commonly present in herbs and foodstuffs, and exhibit hepatotoxicity requiring metabolic activation by cytochrome P450 3A to form the electrophilic metabolites-pyrrolic esters. PAs also cause embryo toxicity, but the metabolic profiles of PAs in fetus and placenta have been far from clear. In this study, we determined the basal metabolic activation of retrorsine (RTS) in rat maternal liver, placenta, and fetal liver in vitro and examined the fetal toxicity and bioactivation of RTS in vivo. Detection of microsomal RTS metabolites in vitro showed that the basal metabolic activity of fetal liver and placenta to RTS was much weaker than that of maternal liver. In addition, a higher rate of pyrrolic ester formation was found in normal male fetal liver compared with that of female pups. In vivo exposure to RTS caused fetal growth retardation, as well as placental and fetal liver injury. Little difference in serum RTS was observed in dams and fetuses, but the content of pyrrole-protein adduction in the fetal liver was much lower than that in maternal liver, which was consistent with basal metabolic activity. Unexpectedly, compared with basal metabolism in fetal liver, exposure to RTS during middle and late pregnancy caused an opposite gender difference in RTS metabolism and CYP3A expression in the fetal liver. For the first time, our study showed that RTS can permeate the placenta barrier and entering fetal circulation, whereas the intrauterine pyrrolic metabolite was generated mainly by fetal liver but not transported from the maternal circulation. Induction of CYP3A by RTS was gender-dependent in the fetal liver, which was probably responsible for RTS-induced fetal hepatic injury, especially for female pups.
    Print ISSN: 0090-9556
    Electronic ISSN: 1521-009X
    Topics: Chemistry and Pharmacology , Medicine
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  • 5
    Publication Date: 2018-03-06
    Description: Cholesterol 25-hydroxylase (CH25H) catalyzes the production of 25-hydroxycholesterol (25-HC), an oxysterol that can play an important role in different biological processes. However, the mechanisms regulating CH25H expression have not been fully elucidated. In this study, we determined that CH25H is highly expressed in mouse liver and peritoneal macrophages. We identified several liver X receptor (LXR) response elements (LXREs) in the human CH25H promoter. In HepG2 cells, activation of LXR by 25-HC or other oxysterols and synthetic ligands [T0901317 (T317) and GW3965] induced CH25H protein expression, which was associated with increased CH25H mRNA expression. 25-HC or T317 activated CH25H transcription in an LXRE-dependent manner. Thus, high-expressing LXRα or LXRβ activated CH25H expression, and the activation was further enhanced by LXR ligands. In contrast, inhibition of LXRα/β expression attenuated 25-HC or T317-induced CH25H expression. Deficiency of interferon expression reduced, but did not block, LXR ligand-induced hepatic CH25H expression. Activation of LXR also substantially induced macrophage CH25H expression. In vivo, administration of GW3965 to mice increased CH25H expression in both liver and peritoneal macrophages. Taken together, our study demonstrates that 25-HC can activate CH25H expression in an LXR-dependent manner, which may be an important mechanism to exert the biological actions of 25-HC.
    Print ISSN: 0022-2275
    Electronic ISSN: 1539-7262
    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 6
    ISSN: 1573-2878
    Keywords: vector optimization ; set-valued maps ; generalized convexity ; equivalent conditions ; theorem of the alternatives ; optimality conditions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract In this paper, the concept of generalized cone subconvexlike set-valued mapsis presented and a theorem of alternative for the system of generalizedinequality–equality set-valued maps is established. By applying thetheorem of the alternative and other results, necessary and sufficientoptimality conditions for vector optimization problems with generalizedcone subconvexlike set-valued maps are obtained.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: Photodissociation of the H2S molecule at 157.6 nm was studied experimentally using the Rydberg tagging technique. Translational energy distributions of the H-atom product from the H2S photodissociation were measured, and the SH(X 2Π)+H(2S) channel was found to be the dominant dissociation process. Spin-orbit and rovibrational state distributions were also obtained for the SH product, which was found to be both vibrationally and rotationally excited. An intriguing bimodal rotational distribution in the lowest two vibrational states, v=0 and 1, has been clearly observed for the SH product, indicating that there are two distinctive dissociation mechanisms involved in the photodissociation of H2S at 157 nm excitation. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 8
    Publication Date: 2018-04-24
    Description: Functional maturation of liver sinusoidal endothelial cells (LSECs) induced by a NOD1 ligand (diaminopimelic acid [DAP]) during viral infection has not been well defined. Thus, we investigated the role of DAP-stimulated LSEC maturation during hepatitis B virus (HBV) infection and its potential mechanism in a hydrodynamic injection (HI) mouse model. Primary LSECs were isolated from wild-type C57BL/6 mice and stimulated with DAP in vitro and in vivo and assessed for the expression of surface markers as well as for their ability to promote T cell responses via flow cytometry. The effects of LSEC maturation on HBV replication and expression and the role of LSECs in the regulation of other immune cells were also investigated. Pretreatment of LSECs with DAP induced T cell activation in vitro. HI-administered DAP induced LSEC maturation and subsequently enhanced T cell responses, which was accompanied by an increased production of intrahepatic cytokines, chemokines, and T cell markers in the liver. The HI of DAP significantly reduced the HBsAg and HBV DNA levels in the mice. Importantly, the DAP-induced anti-HBV effect was impaired in the LSEC-depleted mice, which indicated that LSEC activation and T cell recruitment into the liver were essential for the antiviral function mediated by DAP application. Taken together, the results showed that the Ag-presenting ability of LSECs was enhanced by DAP application, which resulted in enhanced T cell responses and inhibited HBV replication in a mouse model.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 9
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie; 72. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 94. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 49. Tagung des Berufsverbandes der Fachärzte für Orthopädie; 20081022-20081025; Berlin; DOCEF18-244 /20081016/
    Publication Date: 2008-10-17
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 10
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  21. Jahrestagung der Retinologischen Gesellschaft gemeinsam mit dem 8. Symposium der International Society of Ocular Trauma; 20080619-20080622; Würzburg; DOCISOTRG2008V077 /20080618/
    Publication Date: 2008-06-18
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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