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  • 1
    Language: English
    In: PLoS One, CA: Public Library of Science
    Description: This article explores the interrelationship between the urinary microbiota and host antimicrobial peptides as mechanisms for urinary tract infection risk.
    Keywords: Resident Bacterial Communities ; Host Antimicrobial Peptides ; Urinary Tract Infection
    ISSN: 19326203
    E-ISSN: 19326203
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  • 2
    Language: English
    In: Translational Research, 2010, Vol.156(2), pp.98-105
    Description: Activating V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene mutations are important predictive markers for antiepidermal growth factor receptor chemotherapy in colorectal cancer (CRC). However, a rapid and accurate assay for KRAS/BRAF mutation detection from routine pathological specimens is lacking in clinical practice. We applied the cycleave polymerase chain reaction (PCR) method to routine KRAS/BRAF genotyping of CRC patients at our institution from 2001 to 2009. The accuracy of cycleave PCR genotyping was shown by the high concordance with reverse transcriptase-PCR-coupled direct sequencing. KRAS gene mutations were analyzed successfully from small biopsy or cytology specimens. Although some surgical specimens could not be evaluated by cycleave PCR, corresponding biopsy specimens could be used instead. This PCR failure observed for some biopsy specimens may have been a result of the use of formalin fixation, as overfixation of surgical specimens by formalin impaired PCR amplification. In conclusion, cycleave PCR is practically applicable to KRAS/BRAF genotyping using small amounts of biopsied tumor cells. Care must be taken in the selection of pathological specimens for KRAS/BRAF testing.
    Keywords: Medicine
    ISSN: 1931-5244
    E-ISSN: 1878-1810
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  • 3
    Language: English
    In: Journal of Clinical Microbiology, pp. 1376-1383
    Description: Article on evidence of uncultivated bacteria in the adult female bladder.
    Keywords: Uropathogens ; Clinical Cultivation ; Uncultivated Bacteria ; Urinary Tract Conditions
    ISSN: 1098660X
    E-ISSN: 1098660X
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  • 4
    Language: English
    In: International Urogynecology Journal, 2014, Vol.25(9), pp.1179-1184
    Description: Byline: Linda Brubaker (1), Charles W. Nager (2), Holly E. Richter (3), Anthony Visco (4), Ingrid Nygaard (5), Matthew D. Barber (6), Joseph Schaffer (7), Susan Meikle (8), Dennis Wallace (9), Noriko Shibata (10), Alan J. Wolfe (10) Keywords: Microbiome; Urinary bacteria; Urinary urgency incontinence; Urinary tract infection Abstract: Introduction and hypothesis This study's aims were to detect and quantify bacterial DNA in the urine of randomized trial participants about to undergo treatment for urinary urgency incontinence (UUI) without clinical evidence of urinary tract infection (UTI) and to determine if the presence of bacterial DNA in baseline urine relates to either baseline urinary symptoms or UTI risk after urinary tract instrumentation. Methods Women without clinical evidence of baseline UTI were randomized to cystoscopic onabotulinum toxin A injection and oral placebo medication versus cystoscopic placebo injection and active oral medication. Bacterial DNA in participants' catheterized urine was measured by quantitative polymerase chain reaction (qPCR). Results Bacterial DNA was detected in the urine of 38.7 % of participants (60 out of 155). In these 60 qPCR-positive participants, baseline daily UUI episodes were greater than in the 95 qPCR-negative participants (5.71 [[+ or -]2.60] vs 4.72 [[+ or -]2.86], p=0.004). Neither symptom severity by questionnaire nor treatment outcome was associated with qPCR status or with qPCR level in qPCR-positive subjects. In contrast, the presence of urinary bacterial DNA was associated with UTI risk: only 10 % of the qPCR-positive women developed a UTI post-treatment, while 24 % of the qPCR-negative women did so. The median qPCR level for qPCR-positive samples did not differ significantly by UTI status (UTI 2.58x10.sup.5 vs no UTI 1.35x10.sup.5 copies/mL, p=0.6). Conclusions These results may indicate a urinary bacterial contribution to both baseline UUI and the risk of post-treatment UTI. Author Affiliation: (1) Departments of Obstetrics and Gynecology and Urology, Stritch School of Medicine, Loyola University Chicago, 2160 S. First Avenue, Boulevard 120, Room 420, Maywood, IL, 60153, USA (2) Department of Reproductive Medicine, UC San Diego Health System, San Diego, San Diego, CA, USA (3) Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL, USA (4) Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA (5) Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA (6) Obstetrics, Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH, USA (7) Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA (8) Gynecologic Health and Disease Branch, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA (9) Health Sciences Division, Research Triangle Institute, Research Triangle Park, NC, USA (10) Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA Article History: Registration Date: 29/12/2013 Received Date: 10/10/2013 Accepted Date: 28/12/2013 Online Date: 11/02/2014 Article note: The ABC trial is registered at www.clinicaltrials.gov as NCT01166438.
    Keywords: Microbiome ; Urinary bacteria ; Urinary urgency incontinence ; Urinary tract infection
    ISSN: 0937-3462
    E-ISSN: 1433-3023
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  • 5
    Language: English
    In: Journal of Vascular Surgery, 2011, Vol.54(6), pp.1753-1759
    Description: Intimal hyperplasia is a major obstacle to patency after vein grafting. Several clinical trials revealed that pioglitazone, a peroxisome proliferator-activated receptor-γ ligand, exerts beneficial actions on cardiovascular complications. We investigated whether pioglitazone modulates intimal hyperplasia in experimental rabbit autologous vein grafts. Male Japanese White rabbits were randomly divided into two groups: one group received pioglitazone as food admixture at a concentration of 0.01%, and the other did not (control). One week later, each group underwent reversed autologous vein bypass grafting of the right common carotid artery using ipsilateral external jugular vein. Pioglitazone therapy was continued after surgery and until harvest. Intimal hyperplasia of the grafted vein was assessed at 28 days. Two weeks after implantation, proliferative cells in the neointima were identified by immunohistochemical staining with Ki-67 monoclonal antibody. To determine apoptotic cells, we performed terminal deoxynucleotidyl transferase-mediated deoxyuride-5′-triphosphate nick-end labeling (TUNEL) staining. Blood samples were collected at 28 days after implantation for measuring metabolic parameters such as plasma glucose and total cholesterol. Adiponectin levels were determined by Western blot analysis. Finally, we assessed adiponectin-related signaling pathway, 5′ adenosine monophosphate-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK) in the grafted vein by Western blot analysis. Treatment with pioglitazone markedly inhibited intimal hyperplasia of carotid interposition-reversed jugular vein grafts in the pioglitazone group (0.54 ± 0.04 mm ) vs control (0.93 ± 0.04 mm ; n = 7; 〈 .01). Pioglitazone treatment reduced the number of Ki-67-positive proliferating cells in the neointima of the vein grafts at 14 days after implantation in the pioglitazone group (4.1% ± 1.1%) vs the controls (16.8% ± 1.7%; 〈 .05). The frequency of TUNEL-positive apoptotic cells was enhanced by pioglitazone (3.5% ± 0.5%) vs the controls (1.2% ± 0.1%; 〈 .05). Pioglitazone treatment also increased plasma levels of adiponectin, a vascular protective hormone, and led to an increase in phosphorylation of AMPK and a decrease in phosphorylation of ERK in the grafted vein. Pioglitazone attenuates intimal hyperplasia of the vein graft after autologous bypass grafting by its ability to suppress cell proliferation and enhance apoptosis. Pioglitazone could represent a therapeutic target for the prevention of graft failure after bypass grafting. Intimal hyperplasia is a major obstacle to patency after vein grafting. Various treatments to reduce neointimal hyperplasia have been examined; however, a standard clinical treatment has not yet been established. We report that pioglitazone, a peroxisome proliferator-activated receptor-γ ligand, inhibits intimal hyperplasia of autologous vein grafts. Pioglitazone also increased adiponectin, an adipose-derived hormone. Obesity-related complications, such as diabetes, are closely associated with autologous vein graft stenosis after bypass surgery. The findings reported here suggest that pharmacologic approaches aimed at increasing adiponectin production, such as pioglitazone, can contribute to the prevention of autologous vein graft stenosis in obese individuals.
    Keywords: Medicine
    ISSN: 0741-5214
    E-ISSN: 1097-6809
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  • 6
    Language: English
    In: Environmental Health, 01 October 2008, Vol.7(1), p.47
    Description: Abstract Background The Yusho poisoning incident, which was caused by rice bran oil contaminated with polychlorinated biphenyls (PCBs), polychlorinated quarterphenyls (PCQs) and polychlorinated dibenzofurans (PCDFs) generated by heat denaturation of PCB, occurred in 1968 in western Japan. Annual...
    Keywords: Medicine
    ISSN: 1476-069X
    E-ISSN: 1476-069X
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  • 7
    Language: English
    In: Biomaterials, April 2015, Vol.47, pp.62-71
    Description: The nanoscale structure-function relationship is a key determinant of bone toughness or micro-fragility. The loss of bone toughness during the aging process has been accepted based on empirical evidence, but this concept has not yet been fully supported by evidence at the material level. Here, we demonstrate a reduction in bone toughening mechanism in mimetic aged cortical bone obtained from deficient ( ) mice and assessed by dynamic mechanical analysis. The strain-rate nanoindentation tests showed enhanced stiffening of the wild-type calvarial bone and a large dimensional recovery during rapid loading following the constant displacement test. Such strain-dependent stiffening was likely associated with nanoscale dilatational bands and subsequent strain-energy transfer to the superior wild-type cross-linked collagen matrix network. The absence of dilatational bands formed by hydroxyapatite crystals and non-collagenous proteins in the bone samples likely diminished the intrinsic bone toughening mechanisms almost independent of viscoelastic behaviors. Such nanoscale structural alternations that occur during aging processes lead to crack propagation and result in overall bone fractures under large external stresses. In addition, dynamic mechanical analysis using instrumented nanoindentation was useful for the evaluation of bone mechanical properties in this pathological model of a genetic knockout mouse.
    Keywords: Bone ; Mechanical Properties ; Ageing ; Dynamic Mechanical Analysis ; Nanoindentation ; Medicine ; Engineering
    ISSN: 0142-9612
    ISSN: 20452322
    E-ISSN: 1878-5905
    E-ISSN: 20452322
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  • 8
    Language: English
    In: The Journal of Allergy and Clinical Immunology, April 2016, Vol.137(4), pp.1226-1235
    Description: The circadian clock temporally gates signaling through the high-affinity IgE receptor (FcεRI) in mast cells, thereby generating a marked day/night variation in allergic reactions. Thus manipulation of the molecular clock in mast cells might have therapeutic potential for IgE-mediated allergic reactions. We determined whether pharmacologically resetting the molecular clock in mast cells or basophils to times when FcεRI signaling was reduced (ie, when core circadian protein period 2 [PER2] is upregulated) resulted in suppression of IgE-mediated allergic reactions. We examined the effects of PF670462, a selective inhibitor of the key clock component casein kinase 1δ/ε, or glucocorticoid, both of which upregulated PER2 in mast cells, on IgE-mediated allergic reactions both and . PF670462 or corticosterone (or dexamethasone) suppressed IgE-mediated allergic reactions in mouse bone marrow–derived mast cells or basophils and passive cutaneous anaphylactic reactions in mice in association with increased PER2 levels in mast cells or basophils. PF670462 or dexamethasone also ameliorated allergic symptoms in a mouse model of allergic rhinitis and downregulated allergen-specific basophil reactivity in patients with allergic rhinitis. Pharmacologically resetting the molecular clock in mast cells or basophils to times when FcεRI signaling is reduced can inhibit IgE-mediated allergic reactions. The results suggest a new strategy for controlling IgE-mediated allergic diseases. Additionally, this study suggests a novel mechanism underlying the antiallergic actions of glucocorticoids that relies on the circadian clock, which might provide a novel insight into the pharmacology of this drug in allergic patients.
    Keywords: Circadian Clock ; Mast Cells ; Basophils ; Ige ; Allergy ; Medicine
    ISSN: 0091-6749
    E-ISSN: 1097-6825
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  • 9
    In: PLoS ONE, 2014, Vol.9(3)
    Description: Oral phosphate loading and calcitriol stimulate Fibroblast growth factor 23 (FGF23) secretion, but the mechanisms underlying the stimulation of FGF23 remain to be studied. We compared the effect of intravenous phosphate loading with that of oral loading on FGF23 levels in normal and 5/6 nephrectomized uremic rats. Uremic rats (Nx) and sham-operated rats were fed a normal phosphate diet for 2 weeks and then divided into 3 groups: 1) with the same phosphate diet (NP), 2) with a high phosphate diet (HP), and 3) NP rats with intravenous phosphate infusion using a microinfusion pump (IV). Blood and urine were obtained 1 day (early phase) and 7 days (late phase) after the interventions. In the early and late phases, serum phosphate levels and fractional excretion of phosphate (FEP) were comparable in the HP and IV groups in both Sham and Nx rats. Serum phosphate levels in the HP and IV groups were equally and significantly higher than those in the NP group only in the late phase in Nx rats. In the early phase, FGF23 levels were comparable in the NP, HP, and IV groups, but were significantly higher in the HP and IV groups compared to the NP group in the late phase in Nx rats. 1α-hydroxylase and sodium dependent phosphate co-transporter 2a expression levels in the kidney in Nx rats were equally and significantly decreased in the HP and IV groups compared with the NP group, while 24-hydroxylase expression was equally and significantly increased. These results show that chronic intravenous phosphate loading increases bioactive FGF23, indicating that an alternative pathway for FGF23 regulation, in addition to the dietary route, may be present. This pathway is clearer under conditions produced by a kidney injury in which phosphate is easily overloaded.
    Keywords: Research Article ; Biology ; Medicine ; Veterinary Science
    E-ISSN: 1932-6203
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  • 10
    Language: English
    In: Nanomedicine: Nanotechnology, Biology, and Medicine, October 2013, Vol.9(7), pp.1036-1047
    Description: Bone morphogenetic protein-2 (BMP2) is among the most popular anabolic agents and substantially increase bone volume related to enhanced osteoblast differentiation. Here we demonstrate a remarkable deterioration in the nanomechanical properties of mineralized tissue induced from osteoblasts solely by the function of BMP2. Mineralized tissue of primary osteoblasts cultured with BMP2 shows molecular features of both bone and cartilage, but depletion of lysyl oxidase family members leads to poor nanomechanical properties of the mineralized tissue. Lysyl oxidase like-2 supplementation reinforces the inferior mineralized tissue induced from osteoblasts by BMP2 through intermolecular cross-linking of type II or type X collagen-rich extracellular matrix. This may also mimic a consolidation of bone fracture gaps, despite the fact that the distribution of the bone properties in such microenvironments has been poorly elucidated. These findings confirm the importance of testing newly induced bone down to the microscale and nanoscale in bone tissue engineering. Bone morphogenetic protein-2 is known to substantially increase bone volume related to enhanced osteoblast differentiation; however, this team of investigators report a remarkable deterioration in the nanomechanical properties of mineralized tissue induced from osteoblasts solely by the function of BMP2. Five indentation tests on an mineralize tissue. With the loading/partial unloading test, we can obtain constant hardness and elastic modulus on mineralized tissue along with indenter penetration.
    Keywords: Nanoindentation ; Raman Spectroscopy ; Osteoblasts ; Bone Morphogenetic Protein-2 ; Lysyl Oxidase Like-2 ; DNA Microarray ; Medicine
    ISSN: 1549-9634
    E-ISSN: 1549-9642
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