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1.
Karin R. Engelhardt Yaobo Xu Angela Grainger Mila G. C. Germani Batacchi David J. Swan Joseph D. P. Willet Intan J. Abd Hamid Philipp Agyeman Dawn Barge Shahnaz Bibi Lucy Jenkins Terence J. Flood Mario Abinun Mary A. Slatter Andrew R. Gennery Andrew J. Cant Mauro Santibanez Koref Kimberly Gilmour Sophie Hambleton 《Journal of clinical immunology》2017,37(1):42-50
Purpose
We aimed to achieve a retrospective molecular diagnosis by applying state-of-the-art genomic sequencing methods to past patients with T-B+NK+ severe combined immunodeficiency (SCID). We included identification of copy number variations (CNVs) by whole exome sequencing (WES) using the CNV calling method ExomeDepth to detect gene alterations for which routine Sanger sequencing analysis is not suitable, such as large heterozygous deletions.Methods
Of a total of 12 undiagnosed patients with T-B+NK+ SCID, we analyzed eight probands by WES, using GATK to detect single nucleotide variants (SNVs) and small insertions and deletions (INDELs) and ExomeDepth to detect CNVs.Results
We found heterozygous single- or multi-exon deletions in IL7R, a known disease gene for autosomal recessive T-B+NK+ SCID, in four families (seven patients). In three families (five patients), these deletions coexisted with a heterozygous splice site or nonsense mutation elsewhere in the same gene, consistent with compound heterozygosity. In our cohort, about a quarter of T-B+NK+ SCID patients (26%) had such compound heterozygous IL7R deletions.Conclusions
We show that heterozygous IL7R exon deletions are common in T-B+NK+ SCID and are detectable by WES. They should be considered if Sanger sequencing fails to detect homozygous or compound heterozygous IL7R SNVs or INDELs.2.
Qiongyi Hu Yue Sun Yuan Li Hui Shi Jialin Teng Honglei Liu Xiaobing Cheng Junna Ye Yutong Su Yufeng Yin Mengru Liu Jiucun Wang Chengde Yang 《BMC immunology》2018,19(1):38
Background
Little is known about the presence of specific autoantibodies in ankylosing spondylitis (AS), an immune-mediated inflammatory disease. The object of this study was to explore potential autoantibody profiles in AS patients.Results
Levels of anti-SIRT1 autoantibodies were significantly higher in AS (P?< 0.001) and psoriatic arthritis (PsA) (P?<?0.01) patients but not rheumatoid arthritis (RA) patients compared with healthy controls. Additionally, titers of anti-NAD-dependent protein deacetylase sirtuin-1(SIRT1) antibodies were significantly higher in AS patients than in RA (P?<?0.05) and PsA (P?<?0.05) patients. Moreover, levels of anti-SIRT1 (P?<?0.001) antibodies were significantly higher during the first year in patients with hip joint involvement. The anti-SIRT1 antibody positivity rate was 18.9% in AS patients.Conclusions
Our findings indicate that anti-SIRT1 autoantibodies may serve as a marker for diagnosing AS and predicting hip joint involvement at an early stage.3.
Nicolas Degand Justine Dautremer Benoît Pilmis Agnès Ferroni Fanny Lanternier Julie Bruneau Olivier Hermine Stéphane Blanche Xavier Nassif Olivier Lortholary Marc Lecuit 《Journal of clinical immunology》2017,37(7):727-731
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Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases.Purpose
We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis.Methods
16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis.Results
Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin.Conclusion
In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.4.
Stephan?L.?Haas Christel?Wei? Peter?Bugert Jutta?Gundt Heiko?Witt Manfred?V.?Singer Thomas?Berg Ulrich?B?cker 《Journal of clinical immunology》2009,29(5):620-628
Background
Recently, two functional IL18 promoter variants, ?607C>A (rs1946518) and ?137G>C (rs187238), were associated with viral clearance in patients with hepatitis C. The present study focused on their relevance for treatment response.Methods
Seven hundred fifty-seven chronically infected European patients and 791 controls were enrolled in the study. IL18 genotyping was performed by allele-specific PCR. Liver histology was available in 67.9%.Results
Genotype and allele frequencies were equally distributed in patients and controls. No significant association with various disease characteristics was observed. However, when comparing patients with sustained virological response (SR) and non-SR, statistically significant associations were found for both variants (p?=?0.0416 and p?=?0.0274, respectively). In viral genotype 1, the ?607A allele was positively associated with treatment response (p?=?0.0190; OR 1.537; 95% CI, 1.072–2.205) and the ?137G allele with a higher rate of nonresponse (p?=?0.0302; OR 1.524; 95% CI, 1.040–2.233).Conclusions
The association of IL18 variants with treatment response in genotype 1 hepatitis C patients implies a predictive and modifying role of these genetic variants.5.
Alessio Cortelazzo Claudio de Felice Silvia Leoncini Cinzia Signorini Roberto Guerranti Roberto Leoncini Alessandro Armini Luca Bini Lucia Ciccoli Joussef Hayek 《Inflammation research》2017,66(3):269-280
Background
Mutations in the cyclin-dependent kinase-like 5 gene cause a clinical variant of Rett syndrome (CDKL5-RTT). A role for the acute-phase response (APR) is emerging in typical RTT caused by methyl-CpG-binding protein 2 gene mutations (MECP2-RTT). No information is, to date, available on the inflammatory protein response in CDKL5-RTT. We evaluated, for the first time, the APR protein response in CDKL5-RTT.Methods
Protein patterns in albumin- and IgG-depleted plasma proteome from CDKL5-RTT patients were evaluated by two-dimensional gel electrophoresis/mass spectrometry. The resulting data were related to circulating cytokines and compared to healthy controls or MECP2-RTT patients. The effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) were evaluated.Results
CDKL5-RTT mutations resulted in a subclinical attenuated inflammation, specifically characterized by an overexpression of the complement component C3 and CD5 antigen-like, both strictly related to the inflammatory response. Cytokine dysregulation featuring a bulk increase of anti-inflammatory cytokines, predominantly IL-10, could explain the unchanged erythrocyte sedimentation rate and atypical features of inflammation in CDKL5-RTT. Omega-3 PUFAs were able to counterbalance the pro-inflammatory status.Conclusion
For the first time, we revealed a subclinical smouldering inflammation pattern in CDKL5-RTT consisting in the coexistence of an atypical APR coupled with a dysregulated cytokine response.6.
M. S. Chung J. Kim J. O. Kang H. Pai 《European journal of clinical microbiology & infectious diseases》2016,35(11):1771-1776
Purpose
The purpose of this study was to investigate the impact of malignancy and chemotherapy on the clinical and microbiological characteristics of Clostridium difficile infections (CDI).Methods
CDI patients with a history of malignancy within 5 years were defined as the cancer group. The characteristics of the patients were compared according to the presence of malignancy.Results
Of 580 patients with CDI, 159 (27.4 %) belonged to the cancer group and 421 (72.6 %) to the non-cancer group. More of the patients in the cancer group than those in the non-cancer group had been hospitalized within the prior 2 months (P?<?0.001). Leukocytosis was more common in the non-cancer group (P?=?0.034), while infection by PCR ribotype 017 strains was more common in the cancer group, with marginal significance (P?=?0.07). Recurrence was more frequent in the cancer group (20.4 % vs. 9.5 %, P =0.005) and cancer was an independent risk factor for recurrence of CDI (OR?=?2.66, 95 % CI 1.34-5.29, P =0.005). Age also contributed to the recurrence of CDI (OR?=?1.03, 95 % CI 1.00-1.06, P =0.026).Conclusions
Malignancy and age are independent risk factors for recurrence of CDI. Cancer patients require careful observation for recurrence after treatment of CDI.7.
Background
The focus on translational research in clinical trials has the potential to generate clinically relevant genetic data that could have importance to patients. This raises challenging questions about communicating relevant genetic research results to individual patients.Methods
An exploratory pharmacogenetic analysis was conducted in the international ovarian cancer phase III trial, AGO-OVAR 16, which found that patients with clinically important germ-line BRCA1/2 mutations had improved progression-free survival prognosis. Mechanisms to communicate BRCA results were evaluated, because these findings may be beneficial to patients and their families.Results
Communicating individual BRCA results was not anticipated during clinical trial design. Consequently, options were not available for patients to indicate their preference for receiving their individual results when they signed pharmacogenetic informed consent. Differences in local requirements, clinical practice, and opinion regarding the ethical aspects of how to convey genetic results to patients are all potential barriers to returning individual BRCA results to patients. Communicating the aggregate BRCA result from this study provided clinical investigators with a mechanism to disseminate the overall study finding to patients while taking individual circumstances, local guidelines and clinical practice into account.Conclusion
This study illustrates the importance of increasing the clarity and scope of informed consent and the need for patient engagement to ensure clinical trial participants can indicate their preference regarding receipt of potentially important individual pharmacogenetic results.Trial registration
This study was registered in the NCT Clinical Trial Registry under NCT00866697 on March 19, 2009, following approval from participating ethics committees (Additional file 1).8.
C. Sanfilippo D. Cambria A. Longo M. Palumbo R. Avola M. Pinzone G. Nunnari F. Condorelli G. Musumeci R. Imbesi P. Castogiovanni L. Malaguarnera Michelino Di Rosa 《Inflammation research》2017,66(12):1107-1116
Objective
The HIV-1 virus activates the complement system, an essential element of the immune system. SERPING1 is a protease inhibitor that disables C1r/C1s in the C1 complex of the classical complement pathway.Methods
In this paper, we performed an analysis of several microarrays deposited in GEO dataset to demonstrate that SERPING1 mRNA is modulated in CD14+ monocytes from HIV-1-infected individuals. In addition, data were validated on monocytes isolated from seronegative healthy volunteers, treated with IFNs.Results
Our analysis shows that SERPING1 mRNA is overexpressed in monocytes from HIV-1+ patients and the expression levels correlate positively with viral load and negatively with the CD4+ T-cell count. Of note, anti-retroviral therapy is able to reduce the levels of SERPING1 mRNA, ex vivo. In addition, we found that 30% of the SERPING1 genes network is upregulated in monocytes from HIV-1+ patients. Noteworthy, the expression levels of IFITM1—an antiviral molecule belonging to the genes network—correlate positively with SERPING1 expression. Interestingly, the monocytes treatment with IFN-gamma, IFN-beta and IFN-alpha significantly upregulates the SERPING1 mRNA expression levels.Conclusions
From the outcome of our investigation, it is possible to conclude that SERPING1 and its network serve as important components of the innate immune system to restrict HIV-1 infection.9.
M. Yaqoob L. P. Wang J. Memon J. Kashif S. Umar Z. Naseer M. F. Iqbal M. Fiaz C. P. Lu 《Molecular Genetics, Microbiology and Virology》2017,32(1):49-54
Introduction
We investigated the role of topoisomerase mutations, increased level of the multidrug efflux pump AcrAB, and the plasmid-borne genes (qnr) in the fluoroquinolone (FQ) resistant avian Escherichia coli simultaneously.Material and method
Here, we used four FQs (ciprofloxacin, enrofloxacin, ofloxacin and pefloxacin) and eight clinical isolates of E. coli containing six fluoroquinolone-resistant and two fluoroquinolone- susceptible. PCR and direct sequencing methods were used to detect the role of regulator/ repressor gene (acrR).Objective
The objective of this study was to determine the relationship of these resistance mechanisms for fluoroquinolone resistance.Result
The results showed that (i) all four fluoroquinolone- resistant isolates have topoisomerase mutation and plasmid borne genes qnrS and aac(6')-Ib; (ii) three FQ (enrofloxacin, ofloxacin and pefloxacin) resistant isolates harboring qnrS genes; (iii) two FQ (ciprofloxacin and pefloxacin) resistant isolates had topoisomerase mutation and plasmid borne gene qnrS; (iv) all fluoroquinolone susceptible were not harboring qnrS gene and topoisomerase mutation (v) All isolates were negative for qnrA and qnrB.Conclusion
We found that FQs resistance combination was correlated with synergistically contribution of these resistance mechanisms. Plasmid mediated resistance by qnrS was correlated to pefloxacin resistance but did not correlate to ofloxacin, enrofloxacin and ciprofloxacin. This mechanism might be account for the pefloxacin resistance in avian E. coli.10.
Liang Shen Jiang Xu Lu Luo Haoyu Hu Xiangxiao Meng Xiwen Li Shilin Chen 《Chinese medicine》2018,13(1):58
Background
Diosgenin, mainly extracted from wild diosgenin-contained Dioscorea species, is a well-known starting material of steroidal and contraceptive drugs. However, due to large market demand and increasingly ecological damage, wild Dioscorea species resources available have been gradually declining. Therefore, identification of new potential ecological distribution of diosgenin-contained Dioscorea species is necessary for diosgenin production.Methods
In this study, a large occurrence dataset (1808 data points) of diosgenin-contained Dioscorea species was obtained from Eastern Asia, Southern North America and Southern Africa. Along with the data for six critical environmental parameters and one soil factor, Geographic Information System for Global Medicinal Plant was applied to predict the potential suitable distribution of Dioscorea species.Results
The results showed that the potential distribution of these Dioscorea species covered a wide field, and that new ecological suitability areas were mainly distributed in the central region of South America, the southern part of the European and coastal region of Oceania. Jackknife test indicated that annual precipitation and annual mean radiation were the important climatic factors controlling the distribution of Dioscorea species.Conclusions
The suitable areas and critical climatic factors will serve as a useful guide for diosgenin-contained Dioscorea species conservation and cultivation in ecological suitable areas.11.
Background
Postmenopausal women experience estrogen deficiency-related menopausal symptoms (e.g., hot flashes and mood swings) and a dramatic increase in the incidence of chronic diseases. Although estrogen-replacement therapy (ERT) can reduce mortality from cardiovascular disease and improve osteoporosis and menopausal symptoms, its side effects have limited recent use. This study investigated the estrogen-like activity of aqueous extract from Agrimonia pilosa Ledeb.Methods
The estrogenic activity of A. pilosa was investigated by using several in vitro assays. The binding activity of A. pilosa on estrogen receptors was examined using a fluorescence polarization-based competitive binding assay. The proliferative activity of A. pilosa was also examined using MCF-7 cells. Furthermore, the effect of A. pilosa on the expression of 3 estrogen-dependent genes was assessed.Results
Using liquid chromatography-mass spectrometry, the 3 major peaks of A. pilosa aqueous extract were identified as apigenin-hexose, luteolin-glucuronide, and apigenin-glucuronide. The aqueous extract induced the proliferation of estrogen receptor-positive MCF-7 cells (p?<?0.05). A. pilosa-stimulated proliferation was blocked on adding the estrogen antagonist ICI 182,780. Moreover, A. pilosa treatment increased the mRNA expression of the estrogen-responsive genes pS2 and PR (p?<?0.05).Conclusions
These results suggest A. pilosa can be used to improve estrogen deficiency-related menopausal symptoms or to treat diseases in postmenopausal women.12.
Agnieszka Paradowska-Gorycka Barbara Stypinska Andrzej Pawlik Ewa Haladyj Katarzyna Romanowska-Próchnicka Marzena Olesinska 《Inflammation research》2018,67(5):423-433
Objectives
The aim of the study was to identify HIF-1A genetic variants and their possible association with HIF-1α, VEGF, KDR, RORc and Foxp3 protein levels, and susceptibility to and severity of RA.Methods
The HIF-1A gene polymorphisms were genotyped for 587 RA patients and 341 healthy individuals. The HIF-1α, VEGF, KDR, RORc and Foxp3serum levels were evaluated.Results
Under the codominant model, the frequency of the rs12434438 GG genotype was lower in RA patients than in controls (P?=?0.02). Under the recessive model (AA?+?AG vs GG), the association was also significant (OR 3.32; CI 1.19–9.24; P?=?0.02). Overall, rs12434438 A/G and rs1951795 A/C are in almost completed linkage disequilibrium with D′?=?0.96 and r2?=?0.85. The HIF-1A rs1951795 A allele was associated with rheumatoid factor (P?=?0.02) and mean value of erythrocyte sedimentation rate (ESR) (P?=?0.05). In RA patients with HIF-1A rs12434439 GG genotype, the parameters of disease activity such as DAS-28, VAS score, Larsen score or HAQ score were lower compared to RA patients with the HIF-1A rs12434439 AA genotype. Moreover, we also observed that Foxp3 serum levels were higher, and RORc2 serum levels were lower in RA patients with rs12434439 GG.Conclusion
The polymorphic HIF-1A rs12434439 GG genotype may play a protective role for RA development.13.
Mara A. Correa Tatiane Canhamero Andrea Borrego Iana S. S. Katz José R. Jensen José Luiz Guerra Wafa H. K. Cabrera Nancy Starobinas Jussara G. Fernandes Orlando G. Ribeiro Olga M. Ibañez Marcelo De Franco 《Inflammation research》2017,66(11):969-980
Objective and design
Pristane-induced arthritis (PIA) in AIRmax mice homozygous for Slc11a1 R and S alleles was used to characterize the influence of Slc11a1 gene polymorphism on immune responses during disease manifestation. Previous reports demonstrated that the presence of the Slc11a1 S allele increased the incidence and severity of PIA in AIRmax SS , suggesting that this gene could interact with inflammatory loci to modulate PIA. We investigated the effects of Slc11a1 alleles on the activation of phagocytes during PIA.Treatment
Mice were injected intraperitoneally with two doses of 0.5 mL of mineral oil pristane at 60-day intervals. Arthritis development was accompanied for 180 days.Results
AIRmax SS mice showed differential peritoneal macrophage gene expression profiles during PIA, with higher expression and production of H2O2, NO, IL-1β, IL-6, TNF-α, and several chemokines. The presence of the Slc11a1 R allele, on the other hand, diminished the intensity of macrophage activation, restricting arthritis development.Conclusion
Our data demonstrated the fine-tuning roles of Slc11a1 alleles modulating macrophage activation, and consequent PIA susceptibility, in those mouse lines.14.
Ruqaiyyah Siddiqui Farhat Abjani Chien Ing Yeo Edward R. T. Tiekink Naveed Ahmed Khan 《Journal of negative results in biomedicine》2017,16(1):6
Background
Gold compounds have shown promise in the treatment of non-communicable diseases such as rheumatoid arthritis and cancer, and are considered of value as anti-microbial agents against Gram-negative and Gram-positive bacteria, and have anti-parasitic properties against Schistosoma mansoni, Trypanosoma brucei, Plasmodium falciparum, Leishmania infantinum, Giardia lamblia, and Entamoeba histolytica. They are known to affect enzymatic activities that are required for the cellular respiration processes.Methods
Anti-amoebic effects of phosphanegold(I) thiolates were tested against clinical isolate of A. castellanii belonging to the T4 genotype by employing viability assays, growth inhibition assays, encystation assays, excystation assays, and zymographic assays.Results
The treatment of A. castellanii with the phosphanegold(I) thiolates tested (i) had no effect on the viability of A. castellanii as determined by Trypan blue exclusion test, (ii) did not affect amoebae growth using PYG growth medium, (iii) did not inhibit cellular differentiation, and (iv) had no effect on the extracellular proteolytic activities of A. castellanii.Conclusion
Being free-living amoeba, A. castellanii is a versatile respirator and possesses respiratory mechanisms that adapt to various aerobic and anaerobic environments to avoid toxic threats and adverse conditions. For the first time, our findings showed that A. castellanii exhibits resistance to the toxic effects of gold compounds and could prove to be an attractive model to study mechanisms of metal resistance in eukaryotic cells.15.
Fabiane Sônego Fernanda V. S. Castanheira Catarina V. Horta Alexandre Kanashiro Paula G. Czaikoski Dario S. Zamboni José Carlos Alves-Filho Fernando Q. Cunha 《Inflammation research》2018,67(5):435-443
Objective and design
The objective of this study was to investigate the role of Nod1 in the recruitment of neutrophils into the infection site and in the establishment of the inflammatory response elicited by a clinical isolate strain of P. aeruginosa in vivo, while comparing it to the well-established role of MyD88 in this process.Subjects
Wild-type, Nod1?/? and MyD88?/? mice, all with a C57Bl/6 background.Methods
Mice were intranasally infected with Pseudomonas aeruginosa DZ605. Bronchoalveolar lavage and blood were harvested 6 or 20 h post-infection for evaluating bacterial load, chemokine levels and neutrophil migration. Survival post-infection was also observed.Results
We show here that wild-type and Nod1?/? mice induce similar lung chemokine levels, neutrophil recruitment, and bacterial load, thus leading to equal survival rates upon P. aeruginosa pulmonary infection. Furthermore, we confirmed the essential role of MyD88-dependent signalling in recruiting neutrophils and controlling P. aeruginosa-induced pulmonary infection.Conclusion
The results suggest that in contrast to MyD88, under our experimental conditions, the absence of Nod1 does not impair the recruitment of neutrophils in response to P. aeruginosa DZ605.16.
Chi Zhou Jin Huang Guanglin Cui Hesong Zeng Dao Wen Wang Qiang Zhou 《BMC medical genetics》2018,19(1):219
Background
Fabry disease is an X-linked recessive lysosomal disorder caused by deficient enzymatic activity of α-galactosidase A (α-Gal A). The insufficient enzymatic activity leads to excessive accumulation of glycosphingolipids, the substrates of the enzyme, in lysosomes in organs and tissues. Mutations in the α-Gal A gene (GLA, Xq22) have been proven to be responsible for Fabry disease.Methods
In this study, we report a four-generation pedigree with left ventricular hypertrophy and chronic renal failure that was diagnosed by sequencing the GLA gene. An over expression system was constructed to evaluate the function of the detected mutation.Results
We identified a novel mutation in exon 6 of the GLA gene, p.Asn278Lys, which completely co-segregated with the disease phenotype. The protein level of α-Gal A was significantly lower in the variant group than in the wild-type group; additionally, the pharmacological chaperone 1-deoxy-galactonojirimycin (DGJ) effectively normalized the enzyme activity of α-Gal A and its decline at the protein level.Conclusions
This study is the first to report a novel loss-of-function mutation, p.Asn278Lys, in exon 6 of the GLA gene as a genetic aetiology for Fabry disease. In addition, we analysed the feasibility of DGJ as a therapeutic approach for this particular GLA mutation.17.
Ragheda Yaseen Stefanie Blodkamp Petra Lüthje Friederike Reuner Lena Völlger Hassan Y. Naim Maren von Köckritz-Blickwede 《Journal of negative results in biomedicine》2017,16(1):2
Background
The human leukemia cell line HL-60 is considered an alternative cell culture model to study neutrophil differentiation and migration. The aim of this study was to characterize the suitability of HL-60 cells differentiated to neutrophil-like cells (nHL-60) as substitute for blood-derived human neutrophils to investigate the interaction of neutrophils with Staphylococcus aureus.Methods
For this purpose, antimicrobial activity, bacterial uptake, production of reactive oxygen species and the release of neutrophil extracellular traps (NETs) by nHL-60 cells were analyzed and compared to primary blood-derived neutrophils using Staphylococcus aureus as important human and animal pathogen.Results
Overall, the antimicrobial activities of nHL-60 cells were distinctly lower compared to blood-derived neutrophils. Furthermore, production of reactive oxygen species as well as NET formation was clearly impaired in nHL-60 cells.Conclusion
This study indicates that HL-60 cells are of limited usage as an alternative model to study antimicrobial functions of neutrophils against Staphylococcus aureus.18.
Tippaporn Bualeong Sied Kebir Dorothea Hof Lina Goelz Mathias Graewe Stefan Felix Ehrentraut Pascal Knuefermann Georg Baumgarten Rainer Meyer Heidi Ehrentraut 《Journal of negative results in biomedicine》2016,15(1):9
Background
Toll-like receptors (TLRs) are involved in a variety of cardiovascular disorders, including septic cardiomyopathy, ischemia/reperfusion, heart failure, and cardiac hypertrophy. Previous research revealed that TLR4 promotes cardiac hypertrophy in vivo. Therefore, we investigated whether TLR2 is also involved in the development of cardiac hypertrophy.Methods
Tlr2 deficient and wild type mice were subjected to transverse aortic constriction (TAC) or sham operation procedure. Left ventricular, heart and lung weights as well as hemodynamic parameters were determined after 3, 14 or 28 days. Real-time RT PCR was used to evaluate left ventricular gene expression. Protein content was determined via ELISA.Results
TAC increased systolic left ventricular pressure, contraction and relaxations velocities as well as the heart weight in both genotypes. Tlr2 deficiency significantly enhanced cardiac hypertrophy after 14 and 28 days of TAC. Left ventricular end-diastolic pressure and heart rate increased in Tlr2 ?/? TAC mice only. Fourteen days of TAC led to a significant elevation of ANP, BNP, TGFβ and TLR4 mRNA levels in Tlr2 ?/? left ventricular tissue.Conclusion
These data suggest that Tlr2 deficiency may promote the development of cardiac hypertrophy and ventricular remodeling after transverse aortic constriction.19.
Markos Negash Afework Kassu Bemnet Amare Gizachew Yismaw Beyene Moges 《BMC clinical pathology》2018,18(1):4
Background
Helicobacter pylori antibody titters fall very slowly even after successful treatment. Therefore, tests detecting H. pylori antibody lack specificity and sensitivity. On the other hand, H. pylori stool antigen tests are reported as an alternative assay because of their reliability and simplicity. However, the comparative performance of H. pylori stool antigen tests for detecting the presence of the bacterium in clinical specimens in the study area is not assessed. Therefore, in this study we evaluated the performance of SD BIOLINE H. pylori Ag rapid test with reference to the commercially available EZ- STEP ELISA and SD BIOLINE H. pylori Ag ELISA tests.Methods
Stool samples were collected to analyse the diagnostic performance of SD BIOLINE H. pylori Ag rapid test kit using SD H. pylori Ag ELISA kit and EZ- STEP ELISA tests as a gold standard. Serum samples were also collected from each patient to test for the presence of H. pylori antibodies using dBest H. pylori Test Disk. Sensitivity, specificity, predictive values and kappa value are assessed. P values <?0.05 were taken statistically significant.Results
Stool and serum samples were collected from 201 dyspeptic patients and analysed. The sensitivity, specificity, positive and negative predictive values of the SD BIOLINE H. pylori Ag rapid test were: 95.6% (95% CI, 88.8–98.8), 92.5% (95%CI, 89–94.1%), 86.7% (95% CI, 80.5–89.6), and 97.6% (95% CI, 993.9–99.3) respectively.Conclusion
The performance of SD BIOLINE H. pylori Ag rapid test was better than the currently available antibody test in study area. Therefore, the SD BIOLINE Ag rapid stool test could replace and be used to diagnose active H. pylori infection before the commencement of therapy among dyspeptic patients.20.