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1.
Josef Ehling Matthias Misiewicz Saskia von Stillfried Diana Möckel Jessica Bzyl Sibylle Pochon Wiltrud Lederle Ruth Knuechel Twan Lammers Moritz Palmowski Fabian Kiessling 《Angiogenesis》2016,19(2):245-254
Vascular endothelial growth factor receptor 2 (VEGFR-2) and α v ß 3 integrin are the most frequently addressed targets in molecular imaging of tumor angiogenesis. In preclinical studies, molecular imaging of angiogenesis has shown potential to detect and differentiate benign and malignant lesions of the breast. Thus, in this retrospective clinical study employing patient tissues, the diagnostic value of VEGFR-2, α v ß 3 integrin and vascular area fraction for the diagnosis and differentiation of breast neoplasia was evaluated. To this end, tissue sections of breast cancer (n = 40), pre-invasive ductal carcinoma in situ (DCIS; n = 8), fibroadenoma (n = 40), radial scar (n = 6) and normal breast tissue (n = 40) were used to quantify (1) endothelial VEGFR-2, (2) endothelial α v ß 3 integrin and (3) total α v ß 3 integrin expression, as well as (4) the vascular area fraction. Sensitivity and specificity to differentiate benign from malignant lesions were calculated for each marker by receiver operating characteristics (ROC) analyses. Whereas vessel density, as commonly used, did not significantly differ between benign and malignant lesions (AUROC: 0.54), VEGFR-2 and α v ß 3 integrin levels were gradually up-regulated in carcinoma versus fibroadenoma versus healthy tissue. The highest diagnostic accuracy for differentiating carcinoma from fibroadenoma was found for total α v ß 3 integrin expression (AUROC: 0.76), followed by VEGFR-2 (AUROC: 0.71) and endothelial α v ß 3 integrin expression (AUROC: 0.68). In conclusion, total α v ß 3 integrin expression is the best discriminator between breast cancer, fibroadenoma and normal breast tissue. With respect to vascular targeting and molecular imaging of angiogenesis, endothelial VEGFR-2 appeared to be slightly superior to endothelial α v ß 3 for differentiating benign from cancerous lesions. 相似文献
2.
Torsades de pointes (TdP) is a life-threatening form of ventricular arrhythmia that occurs under conditions of delayed cardiac
repolarization indicated by prolonged QT intervals in ECG recordings. The main mechanism of QT prolongation and TdP is block
of the rapid component of the cardiac delayed rectifier K+ current (IKr), which is encoded by hERG (human ether-à-go-go-related gene). The opioid agonist methadone has previously been demonstrated to inhibit hERG currents, and there are reports
of serious cardiac arrhythmias and deaths from TdP and ventricular fibrillation in patients taking methadone. The aim of the
present study was to compare the effects of the opioid agonists methadone and heroin (3,6-diacetylmorphine) on hERG currents
stably expressed in human embryonic kidney (HEK 293) cells using the whole-cell configuration of the patch-clamp technique.
Both methadone and heroin inhibit hERG currents in a concentration-dependent manner. The following values were calculated
for IC50 (concentration causing half-maximal inhibition) and n (the Hill coefficient): 4.8 μM and 0.9 for methadone, 427 μM and 0.7
for heroin. In conclusion, the potency for block of hERG currents is about 100-fold lower for heroin when compared to methadone. 相似文献
3.
Pruhova S Ek J Lebl J Sumnik Z Saudek F Andel M Pedersen O Hansen T 《Diabetologia》2003,46(2):291-295
AIMS/HYPOTHESIS: The aim of this study was to examine the prevalence and nature of mutations in HNF4alpha/MODY1, GCK/MODY2 and HNF-1alpha/MODY3 genes in Czech subjects with clinical diagnosis of MODY. METHODS: We studied 61 unrelated index probands of Czech origin (28 males, 33 females) with a clinical diagnosis of MODY and 202 family members. The mean age of probands was 22.7+/-12.0 years (range, 6-62) and the mean age at the first recognition of hyperglycaemia was 14.7+/-6.0 years (range, 1-25). The promotor and coding regions inclusive intron exon boundaries of the HNF-4alpha, GCK and HNF-1alpha genes were examined by PCR-dHPLC (HNF-1alpha and GCK) and direct sequencing. RESULTS: We identified 20 different mutations in the HNF-4alpha, GCK and HNF-1alpha in 29 families (48% of all families studied), giving a relative prevalence of 5% of MODY1, 31% of MODY2 and 11.5% of MODY3 among the Czech kindred with MODY. Three of 3, 10 of 11 and 1 of 6 of the mutations identified in HNF-4alpha, GCK and HNF-1alpha respectively, were new. CONCLUSION/INTERPRETATION: Of the families 48% carried mutations in the MODY1-3 genes and of the identified mutations 70% were new. In 52% of Czech families with clinical characteristics of MODY, no mutations were found in the analysed genes. This finding shows that the majority of MODY mutations in a central European population are local and that other MODY genes could be responsible for autosomal dominant transmission of diabetes mellitus. 相似文献
4.
5.
Jost N Acsai K Horváth B Bányász T Baczkó I Bitay M Bogáts G Nánási PP 《Basic research in cardiology》2009,104(1):33-41
Background The aim of the present work was to study the profile of the rapid delayed rectifier potassium current (I
Kr) and the inward rectifier potassium current (I
K1) during ventricular repolarization as a function of action potential duration and rate of repolarization.
Methods Whole cell configuration of the patch clamp technique was used to monitor I
Kr and I
K1 during the action potential plateau and terminal repolarization. Action potentials recorded at various cycle lengths (0.4–5 s)
and repolarizing voltage ramps having various slopes (0.5–3 V/s) were used as command signals. I
Kr and I
K1 were identified as difference currents dissected by E-4031 and BaCl2, respectively.
Results Neither peak amplitudes nor mean values of I
Kr and I
K1 recorded during the plateau of canine action potentials were influenced by action potential duration. The membrane potential
where I
Kr and I
K1 peaked during the terminal repolarization was also independent of action potential duration. Similar results were obtained
in undiseased human ventricular myocytes, and also in canine cells when I
Kr and I
K1 were evoked using repolarizing voltage ramps of various slopes. Action potential voltage clamp experiments revealed that
the peak values of I
Kr, I
K1, and net outward current during the terminal repolarization were independent of the pacing cycle length within the range
of 0.4 and 5 s.
Conclusions The results indicate that action potential configuration fails to influence the amplitude of I
Kr and I
K1 during the ventricular action potential in dogs and humans, suggesting that rate-dependent changes in action potential duration
are not likely related to rate-dependent alterations in I
Kr or I
K1 kinetics in these species.
Returned for 1. Revision: 5 February 2008 1. Revision received: 11 April 2008 Returned for 2. Revision: 14 May 2008 2. Revision
received: 15 May 2008 相似文献
6.
E. van de Vosse T. H. M. Ottenhoff R. A. de Paus E. M. Verhard T. de Boer J. T. van Dissel T. W. Kuijpers 《Infection》2010,38(2):128-130
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare disorder with predisposition to severe, sometimes lethal,
disease caused by otherwise poorly virulent, non-tuberculous environmental mycobacteria and poorly virulent salmonellae. In
patients with MSMD, mutations have been identified in five genes that encode for the proteins IL-12/IL-23p40, IL-12/ IL-23Rβ1, IFN-コR1, IFN-γR2 and STAT1. These proteins play important roles in the type-1 cytokine pathway, which is crucial for human
host defence against intracellular pathogens such as mycobacteria and salmonellae. We report a girl with mild Mycobacterium bovis Bacille Calmette–Guérin (BCG) disease and Salmonella enteritidis cervical lymphadenitis. Despite treatment, she has remained a fecal carrier of S. enteritidis for the past 14 years. She was found to have complete IL-12/IL-23Rβ1 deficiency. A homozygous r.518G>C IL12RB1 mutation was identified, leading to a non-functional R173P substitution in the IL-12/IL-23Rβ1 protein. This mutation abrogated IL-12/IL-23Rβ1 cell-surface expression and resulted in complete lack of T cell responsiveness to both IL-12 and IL-23. 相似文献
7.
Oleksandr M. Maistrenko Svitlana V. Serga Alexander M. Vaiserman Iryna A. Kozeretska 《Biogerontology》2016,17(5-6):785-803
Microbial communities are known to significantly affect various fitness components and survival of their insect hosts, including Drosophila. The composition of symbiotic microbiota has been shown to change with the host’s aging. It is unclear whether these changes are caused by the aging process or, vice versa, they affect the host’s aging and longevity. Recent findings indicate that fitness and lifespan of Drosophila are affected by endosymbiotic bacteria Wolbachia. These effects, however, are inconsistent and have been reported both to extend and shorten longevity. The main molecular pathways underlying the lifespan-modulating effects of Wolbachia remain unclear, however insulin/insulin-like growth factor, immune deficiency, ecdysteroid synthesis and signaling and c-Jun N-terminal kinase pathways as well as heat shock protein synthesis and autophagy have been proposed to play a role. Here we revise the current evidence that elucidates the impact of Wolbachia endosymbionts on the aging processes in Drosophila. 相似文献
8.
Waldhäusl WK 《Diabetologia》2003,46(12):1591-1593
9.
Background
Surveillance cultures may be helpful in identifying patients at increased risk of developing invasive candidiasis. However, only scant information exists on the effect of Candida colonization on serum levels of diagnostic biomarkers. This prospective surveillance study determined the extent of Candida colonization among pediatric cancer patients and its possible impact on serum levels of (1-3)-β-D-glucan (BDG), Candida mannan and Candida DNA. 相似文献10.
Amira A. Moawad Helmut Hotzel Heinrich Neubauer Ralf Ehricht Stefan Monecke Herbert Tomaso Hafez M. Hafez Uwe Roesler Hosny El-Adawy 《Gut pathogens》2018,10(1):39
Background
Poultry remains one of the most important reservoir for zoonotic multidrug resistant pathogens. The global rise of antimicrobial resistance in Gram-negative bacteria is of reasonable concern and demands intensified surveillance.Methods
In 2016, 576 cloacal swabs were collected from 48 broiler farms located in five governorates in northern Egypt. Isolates of Enterobacteriaceae could be cultivated on different media and were identified by MALDI-TOF MS and PCR. Escherichia coli isolates were genotyped by DNA-microarray-based assays. The antimicrobial susceptibility to 14 antibiotics was determined and resistance-associated genes were detected. The VITEK-2 system was applied for phenotypical confirmation of extended-spectrum β-lactamase-producing isolates. The determination of colistin resistance was carried out phenotypically using E-test and genotypically using PCR for detection of the mcr-1 gene.Results
Out of 576 samples, 72 representatives of Enterobacteriaceae were isolated and identified as 63 E. coli (87.5%), 5 Enterobacter cloacae (6.9%), 2 Klebsiella pneumoniae (2.8%) and 2 Citrobacter spp. (2.8%). Seven out of 56 cultivated E. coli (12.5%) were confirmed as ESBL-producing E. coli and one isolate (1.8%) as ESBL/carbapenemase-producing E. coli. Five out of 63 E. coli isolates (7.9%) recovered from different poultry flocks were phenotypically resistant to colistin and harboured mcr-1 gene.Conclusions
This is the first study reporting colistin resistance and emergence of multidrug resistance in Enterobacteriaceae isolated from healthy broilers in the Nile Delta region, Egypt. Colistin-resistant E. coli in poultry is of public health significance. The global rise of ESBL- and carbapenemase-producing Gram-negative bacteria demands intensified surveillance. ESBL-producing E. coli in poultry farms in Egypt are of major concern that emphasizes the possibility of spread of such strains to humans. The results also reinforce the need to develop strategies and to implement specific control procedures to reduce the use of antibiotics.11.
Caetano LC Zucoloto S Kawasse LM Toldo MP do Prado JC 《Digestive diseases and sciences》2008,53(11):2929-2934
In this study, we verified the possible role of cyclophosphamide (CY) in protecting or not against neuronal losses in young
and aged male Calomys callosus chronically infected with the MORC-1 strain of Trypanosoma cruzi through numerical quantification of neurons from the myenteric plexus of the colon and quantification of nitric-oxide concentration
(NO) during the acute and chronic phase of infection. For this purpose, groups of young C. callosus were infected with the MORC-1 strain of T. cruzi. A group of infected animals received i.p. 0.2 mg/ml genuxal dissolved in distilled water treatment with CY. NO concentration
in aged animals displayed reduced levels when compared to those found in young animals. No significant alterations in the
number of neurons were observed in young animals, but for aged ones, a protective role of CY in reducing neuron loss was noted,
in addition to enhancing the neuronal volume, area, and perimeter. These results suggest that CY administration, depending
on the dose and time span, can act as a protective agent against neuronal losses. 相似文献
12.
13.
Dumont SN Lazar AJ Bridge JA Benjamin RS Trent JC 《Journal of cancer research and clinical oncology》2012,138(2):213-220
Purpose
In pediatric alveolar rhabdomyosarcoma, the PAX3–FOXO1 and PAX7–FOXO1 gene fusions are prognostic indicators, while little is known concerning this disease in older patients. To determine whether PAX3/7–FOXO1 fusion gene status correlates with outcome in adolescent, young adult, and adult rhabdomyosarcoma patients, the histological, immunohistochemical, and clinical characteristics of 105 patients followed at The University of Texas MD Anderson Cancer Center from 1957 to 2001 were evaluated. 相似文献14.
Hui Xu Yanxiang Pan Wei Li Haidong Fu Junfeng Zhang Hongqiang Shen Xiucui Han 《Rheumatology international》2016,36(6):829-835
Previous studies suggested that interleukin-17 and Th17 cell play an important role in the pathogenesis of childhood Henoch–Schonlein purpura (HSP). The purpose of our study is to elucidate whether the IL17A and IL17F gene polymorphisms are susceptibility genes for the development of HSP in Chinese children. A total of 148 HSP patients and 202 controls were enrolled for analyzing the single nucleotide polymorphisms (SNP) of IL17A (rs2275913, rs8193037 and rs3819025) and IL17F (rs763780 and rs9463772). TaqMan Real-Time polymerase chain reaction method was used in SNP genotyping. Compared to the healthy controls, the IL17A rs2275913 variant allele A showed a significant association with HSP [odds ratio (OR) 0.70; 95 % CI 0.51–0.94, P = 0.018]. Genotyping analysis demonstrated rs2275913 was associated with a decreased HSP risk (G/A vs. G/G: OR 0.56; 95 % CI 0.33–0.95; A/A vs. G/G: OR 0.46; 95 % CI 0.24–0.86; P = 0.032). Also, our findings showed that the A allele of IL17A rs3819025 was associated with a higher risk of HSP nephritis (OR 1.61; 95 % CI 1.00–2.58; P = 0.047). In addition, a risk haplotype of IL17A (GGA) was found (OR 1.84; 95 % CI 1.17–2.88; P = 0.008). However, no significant differences between HSP patients and healthy controls were observed when comparing genotype, allele or haplotype frequencies of the IL17F rs763780 and rs9463772 polymorphisms. In this study, we confirmed that the rs2275913 polymorphism of the IL17A gene was associated with susceptibility to HSP in Chinese children. However, there was no relationship between IL17F rs763780 and rs9463772 polymorphisms and HSP susceptibility. 相似文献
15.
Goodgame R 《Current infectious disease reports》2003,5(1):66-73
Travel is a risk factor for acquiring infection with a sporeforming protozoa: Cryptosopridium, Cyclospora, Microsporidia, and Isospora. Certain travel destinations have a high disease burden and intense exposure. Patients present with persistent diarrhea and
a history of recent travel to a developing country in the tropics. Very mild infections may be underdiagnosed and may cause
typical traveler’s diarrhea. In a patient with a history of travel and persistent diarrhea unresponsive to the usual antibiotic
and antidiarrhea treatment, stool studies for all four of these protozoa infections should be performed. If immune status
is normal and the disease is mild, symptomatic therapy may suffice. Effective treatment is available for Cyclospora, Microsporidia, and Isospora. 相似文献
16.
Franks PW Jablonski KA Delahanty LM McAteer JB Kahn SE Knowler WC Florez JC;Diabetes Prevention Program Research Group 《Diabetologia》2008,51(12):2214-2223
Aims/hypothesis The single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity associated gene (FTO) and the rs7566605 SNP located 10 kb upstream of the insulin-induced gene 2 gene (INSIG2) have been proposed as risk factors for common obesity.
Methods We tested for genotype–treatment interactions on changes in obesity-related traits in the Diabetes Prevention Program (DPP).
The DPP is a randomised controlled trial of 3,548 high-risk individuals from 27 participating centres throughout the USA who
were originally randomised to receive metformin, troglitazone, intensive lifestyle modification or placebo to prevent the
development of type 2 diabetes. Measures of adiposity from computed tomography were available in a subsample (n = 908). This report focuses on the baseline and 1 year results.
Results The minor A allele at FTO rs9939609 was positively associated with baseline BMI (p = 0.003), but not with baseline adiposity or the change at 1 year in any anthropometric trait. For the INSIG2 rs7566605 genotype, the minor C allele was associated with more subcutaneous adiposity (second and third lumbar vertebrae
[L2/3]) at baseline (p = 0.04). During follow-up, CC homozygotes lost more weight than G allele carriers (p = 0.009). In an additive model, we observed nominally significant gene–lifestyle interactions on weight change (p = 0.02) and subcutaneous (L2/3 [p = 0.01] and L4/5 [p = 0.03]) and visceral (L2/3 [p = 0.02]) adipose areas. No statistical evidence of association with physical activity energy expenditure or energy intake
was observed for either genotype.
Conclusions/interpretation Within the DPP study population, common variants in FTO and INSIG2 are nominally associated with quantitative measures of obesity, directly and possibly by interacting with metformin or lifestyle
intervention.
Trial registration: ClinicalTrials.gov NCT00004992
Funding: The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute
on Aging (NIA), the National Institute of Child Health and Human Development (NICHD), the National Center on Minority Health
and Health Disparities (NCMHD) and the Office of Research on Women’s Health (ORWH).
Electronic supplementary material The online version of this article (doi:) contains supplementary material, including a list of members of the Diabetes Prevention Program Research Group, which is
available to authorised users.
An erratum to this article can be found at 相似文献
17.
Choi KD Kim N Lee DH Kim JM Kim JS Jung HC Song IS 《Digestive diseases and sciences》2007,52(4):960-966
CagA protein of Helicobacter pylori is injected into epithelial cells, and it undergoes tyrosine phosphorylation, resulting in inducing cytoskeletal rearrangements.
A few studies have suggested that the number of CagA tyrosine phosphorylation motifs (EPIYA) and subtypes of CagA were associated
with gastric cancer. This study was performed to characterize the 3' variable regions of the cagA gene of H. pylori and to investigate whether or not there is any relationship between the diversities of cagA and the disease outcome in Korea. Seventy-nine patients (chronic gastritis, 15; duodenal ulcer, 27; benign gastric ulcer,
18; gastric cancer, 19) were enrolled. Biopsy specimens were taken from the antrum for H. pylori culture, and genomic DNA was extracted. PCR and DNA sequence analysis was carried out for the 3′ variable region of the cagA gene. Seventy-eight strains (98.8%) contained three EPIYA motifs and one strain (1.2%) isolated from a patient with duodenal
ulcer contained four EPIYA motifs. Seventy-six strains (96.2%) were the East Asian type. In conclusion, there was no significant
difference between the number of EPIYA motifs or CagA subtypes and various gastroduodenal diseases in Korea. 相似文献
18.
Helicobacter pylori (H. pylori) has been presumed to be an initiating factor in a previously recognized chain of events, starting with active chronic gastritis
and leading to atrophy of the mucosal membrane, intestinal metaplasia, dysplasia (intraepithelial neoplasia), and finally
culminating in gastric carcinoma. Adherence of H. pylori to the gastroduodenal epithelium is believed to be an important step in the induction of active chronic inflammation of the
mucosal layer. However, it is not clear how the pathogen chronically colonizes the gastroduodenal epithelium. In this study,
30 biopsy specimens from H. pylori-positive peptic ulcer (15 for gastric ulcer, 15 for duodenal ulcer) patients were examined by transmission electron microscopy
(TEM) to observe the structural adherence of H. pylori to gastroduodenal epithelium while ten healthy postulants were served as controls. We also investigated the interaction between
H. pylori and gastroduodenal epithelial cells. Morphological appearances of both the pathogen and the cells as well as features of
colonization, attachment, and internalization were observed. H. pylori exhibited both spiral and coccoid forms. Cytoplasmic vacuolar degeneration played by the vacuolating toxin (VacA) was apparent
in gastroduodenal epithelial cells. Specially, a number of tumor cells were found in H. pylori-positive gastric intestinal metaplasia (IM) mucosa under TEM which provided an ultrastructural evidence of IM carrying a
particularly high risk for the development of gastric cancer. 相似文献
19.
Abstract
Background: Metallo-β-lactamase (MBL) is an emerging resistance mechanism among Pseudomonas aeruginosa. The prevalence of this mechanism is particularly high in Latin America. We aimed to describe the prevalence and molecular
characteristics of SPM-1-like, IMP-1-like and VIM type MBLs among ceftazidime and/or imipenem-resistant nosocomial P. aeruginosa isolates.
Methods: Pseudomonas aeruginosa isolates resistant to ceftazidime and/or imipenem recovered from hospitalized patients from two teaching hospitals from Porto
Alegre, Brazil, were prospectively selected. Isolates were tested for MBL production using two phenotypic screening tests.
Those isolates with positive results were further tested for the presence of MBL genes (SPM-1-like, IMP-1-like and VIM type)
and submitted to molecular typing.
Results: A total of 92 isolates were analyzed and 33 (35.9%) were presumptively MBL producers by phenotypic tests. The SPM-1-like gene
was found in 18 isolates and IMP-1-like in 5 isolates. In ten isolates the MBL type could not be identified. Three IMP-1-like
isolates were susceptible to imipenem. SPM-1-like isolates comprised a single clone, and IMP-1-like isolates another single
clone.
Conclusion: The prevalence of MBL production among ceftazidime-resistant P. aeruginosa isolates is relatively high in both hospitals. Infection control measures have been challenged and further improvements in
such measures are required to prevent dissemination of these isolates among hospitals. This is the first report of IMP-1-like
MBLs in P. aeruginosa in southern Brazil. 相似文献
20.
Caetano LC Zucoloto S Kawasse LM Alonsotoldo MP do Prado JC 《Digestive diseases and sciences》2008,53(8):2020-2026
The protective role of cyclophosphamide was studied in this work. Young male Calomys callosus were infected with Trypanosoma cruzi and allowed to age. Cyclophosphamide therapy was administered to animals during acute and late chronic phases of infection. Esophageal neurons were counted, displaying enhanced neuronal loss for the young and treated infected groups. For aged and cyclophosphamide treated animals, a protection was observed through a reduced loss of neurons as compared to the young and infected groups. Enhanced nitric oxide concentrations were observed for young animals as compared to aged counterparts. Splenocyte proliferation was reduced during the acute phase in comparison with those found in the chronic phase. Morphometry of neuronal body displayed a significant reduction concerning the area, perimeter, diameter and volume for aged animals as compared to young groups. These results indicate that the protective effects of cyclophosphamide together with process of neuroplasty of peripheral nervous system could lead to a protection against neuronal loss. 相似文献