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1.
Maria José Franco Brochado Maria Fernanda Chociay Gatti Marco Ant?nio Zago Ana Maria Roselino 《Memórias do Instituto Oswaldo Cruz》2016,111(2):101-105
Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1gene (Nramp1/Slc11a1) is a gene that controls the susceptibility ofinbred mice to intracellular pathogens. Polymorphisms in the humanSlc11a1/Nramp1 gene have been associated with host susceptibilityto leprosy. This study has evaluated nine polymorphisms of theSlc11a1/Nramp1 gene [(GT)n, 274C/T, 469+14G/C, 577-18G/A, 823C/T,1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19patients had the multibacillary and the paucibacillary clinical forms of the disease,respectively), and 239 healthy controls matched by age, gender, and ethnicity. Thefrequency of allele 2 of the (GT)n polymorphism was higher in leprosy patients [p =0.04, odds ratio (OR) = 1.49], whereas the frequency of allele 3 was higher in thecontrol group (p = 0.03; OR = 0.66). Patients carrying the 274T allele (p= 0.04; OR = 1.49) and TT homozygosis (p = 0.02; OR = 2.46), suchas the 469+14C allele (p = 0.03; OR = 1.53) of the 274C/T and 469+14G/Cpolymorphisms, respectively, were more frequent in the leprosy group. The leprosy andcontrol groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A,1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy,while the allele 2 and 3 of the (GT)n polymorphism in the promoter region wereassociated with susceptibility and protection to leprosy, respectively. 相似文献
2.
Rosane Dias Costa Vanessa Amaral Mendon?a Frederico Marianetti Soriani Sandra Lyon Rachel Adriana Penido Ana Maria Duarte Dias Costa Marina Dias Costa Fabio de Souza Terra Mauro Martins Teixeira Carlos Mauricio de Figueiredo Antunes Antonio Lúcio Teixeira 《Memórias do Instituto Oswaldo Cruz》2013,108(8):1051-1056
Leprosy is an infectious and contagious spectral disease accompanied by a series of
immunological events triggered by the host response to the aetiologic agent,
Mycobacterium leprae . The induction and maintenance of the
immune/inflammatory response in leprosy are linked to multiple cell interactions and
soluble factors, primarily through the action of cytokines. The purpose of the
present study was to evaluate the serum levels of tumour necrosis factor (TNF)-α and
its soluble receptors (sTNF-R1 and sTNF-R2) in leprosy patients at different stages
of multidrug treatment (MDT) in comparison with non-infected individuals and to
determine their role as putative biomarkers of the severity of leprosy or the
treatment response. ELISA was used to measure the levels of these molecules in 30
healthy controls and 37 leprosy patients at the time of diagnosis and during and
after MDT. Our results showed increases in the serum levels of TNF-α and sTNF-R2 in
infected individuals in comparison with controls. The levels of TNF-α, but not
sTNF-R2, decreased with treatment. The current results corroborate previous reports
of elevated serum levels of TNF-α in leprosy and suggest a role for sTNF-R2 in the
control of this cytokine during MDT. 相似文献
3.
Aline Garcia Kozlowski Megmar Aparecida dos Santos Carneiro Márcia Alves Dias de Matos Sheila Araújo Teles Jo?o Alves Araújo Filho Koko Otsuki Ana Carolina Paulo Vicente Regina Maria Bringel Martins 《Memórias do Instituto Oswaldo Cruz》2014,109(1):118-121
Human T-cell lymphotropic virus (HTLV) may impact the clinical course of tuberculosis
(TB). Both infections are highly endemic in Brazil. The aim of this study was to
assess the prevalence of HTLV-1/2 in TB patients in Central-West Brazil and to
perform a genetic characterisation of the respective isolates. Of the 402 patients,
six (1.49%) were positive for anti-HTLV and five (1.24%; 95% confidence interval:
0.46-3.05) were infected with HTLV-1/2. Genetic characterisation demonstrated that
the four HTLV-1 isolates belonged to the Transcontinental subgroup A of the
Cosmopolitan subtype a and that the HTLV-2 isolate belonged to subtype a (HTLV-2a/c).
The prevalence of HTLV infection observed in this study is higher than that observed
in local blood donors and the HTLV-1 and 2 subtypes identified are consistent with
those circulating in Brazil. 相似文献
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Luiz Claudio Pereira Ribeiro Cassia Cristina Alves Gon?alves Carla Maria Sena Andrade Slater Silvia Maia Farias de Carvalho Marzia Puccioni-Sohler 《Memórias do Instituto Oswaldo Cruz》2013,108(6):730-734
Intrathecal synthesis of human T-lymphotropic virus type 1 (HTLV-1) antibodies
(Abs) represents conclusive evidence of a specific immune response in the
central nervous system of HTLV-1 associated myelopathy/tropical spastic
paraparesis (HAM/TSP) patients. Western blotting (WB) for HTLV Abs in serum is a
confirmatory test for HTLV-1 infection. The aim of this study was to standardise
the Western blot to demonstrate the intrathecal pattern of Abs against HTLV-1
proteins in HAM/TSP patients. Paired cerebrospinal fluid (CSF) and serum samples
were selected from 20 patients with definite HAM/TSP, 19 HTLV-1 seronegative
patients and two HTLV-1 patients without definite HAM/TSP. The presence of
reactive bands of greater intensity in the CSF compared to serum (or bands in
only the CSF) indicated the intrathecal synthesis of anti-HTLV-1 Abs. All
definite HAM/TSP patients presented with an intrathecal synthesis of anti-HTLV-1
Abs; these Abs were not detected in the control patients. The most frequent
intrathecal targets of anti-HTLV-1 Abs were GD21, rgp46-I and p24 and, to a
lesser extent, p19, p26, p28, p32, p36, p53 gp21 and gp46. The intrathecal
immune response against env (GD21 and rgp46-I) and
gag (p24) proteins represents the most important humoral
pattern in HAM/TSP. This response may be used as a diagnostic marker,
considering the frequent association of intrathecal anti-HTLV-1 Ab synthesis
with HAM/TSP and the pathogenesis of this neurological disease. 相似文献
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Measurements of auto‐antibodies to α‐synuclein in the serum and cerebral spinal fluids of patients with Parkinson's disease 下载免费PDF全文
Rizwan S. Akhtar Joseph P. Licata Kelvin C. Luk Leslie M. Shaw John Q. Trojanowski Virginia M.‐Y. Lee 《Journal of neurochemistry》2018,145(6):489-503
8.
Enhanced susceptibility to seizures modulated by high interleukin‐1β levels during early life malnutrition 下载免费PDF全文
Fabrício Simão Victória Habekost Oliveira Magda Lahourgue Nunes 《Developmental neurobiology》2016,76(10):1150-1159
Early malnutrition in life has permanent consequences on brain development and has been suggested to influence seizure susceptibility. Despite malnutrition is not a direct cause of seizures, we hypothesize that malnutrition may modulate inflammatory response and result in cerebral vulnerability to seizures. In this study, we provide evidence that malnutrition may increase susceptibility to seizures in the postnatal period by interleukin‐1β (IL‐1β) in the hippocampus. Malnourished rats were maintained on a nutritional deprivation regimen from postnatal day 1 (P1) to P10. From P7 to P10, the threshold to seizures induced by flurothyl was used as an index of seizure susceptibility. ELISA and western blot was performed to evaluate levels of IL‐1β, IL‐1R1, PSD‐95 and synapsin. The role of inflammation in the changes of seizure threshold was studied with inhibitors of IL‐1β and IL‐1R1. A significant decrease in body weight and seizure threshold was observed in postnatal malnourished rats. Early malnutrition modulates inflammation by high levels of IL‐1β in hippocampus and in serum. Furthermore, our malnutrition paradigm induced an increase in corticosterone levels. Injection of IL‐1β and IL‐1R1 inhibitors before seizure induction augments seizure threshold in malnourished rats similar to nourished group. Malnutrition did not change PSD‐95 and synapsin expression in the hippocampus. We suggest that malnutrition‐induced inflammation might contribute to seizure susceptibility in the postnatal period. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1150–1159, 2016 相似文献
9.
The Uyghur population and genetic susceptibility to type 2 diabetes: potential role for variants in CAPN10, APM1 and FUT6 genes 下载免费PDF全文
Feifei Zhao Dolikun Mamatyusupu Youxin Wang Honghong Fang Hao Wang Qing Gao Hao Dong Siqi Ge Xinwei Yu Jie Zhang Lijuan Wu Manshu Song Wei Wang 《Journal of cellular and molecular medicine》2016,20(11):2138-2147
Genome‐wide association studies have successfully identified over 70 loci associated with the risk of type 2 diabetes mellitus (T2DM) in multiple populations of European ancestry. However, the risk attributable to an individual variant is modest and does not yet provide convincing evidence for clinical utility. Association between these established genetic variants and T2DM in general populations is hitherto understudied in the isolated populations, such as the Uyghurs, resident in Hetian, far southern Xinjiang Uyghur Autonomous Region, China. In this case–control study, we genotyped 13 single‐nucleotide polymorphisms (SNPs) at 10 genes associated with diabetes in 130 cases with T2DM and 135 healthy controls of Uyghur, a Chinese minority ethnic group. Three of the 13 SNPs demonstrated significant association with T2DM in the Uyghur population. There were significant differences between the T2DM patients and controls in the risk allele distributions of rs3792267 (CAPN10) (P = 0.002), rs1501299 (APM1) (P = 0.017), and rs3760776 (FUT6) (P = 0.031). Allelic carriers of rs3792267‐A, rs1501299‐T, and rs3760776‐T had a 2.24‐fold [OR (95% CI): 1.35–3.71], 0.59‐fold [OR (95% CI): 0.39–0.91], 0.57‐fold [OR (95% CI): 0.34–0.95] increased risk for T2DM respectively. We further confirmed that the cumulative risk allelic scores calculated from the 13 susceptibility loci for T2DM differed significantly between the T2DM patients and controls (P = 0.001), and the effect of obesity/overweight on T2DM was only observed in the subjects with a combined risk allelic score under a value of 17. This study observed that the SNPs rs3792267 in CAPN10, rs1501299 in APM1, and rs3760776 in FUT6 might serve as potential susceptible biomarkers for T2DM in Uyghurs. The cumulative risk allelic scores of multiple loci with modest individual effects are also significant risk factors in Uyghurs for T2DM, particularly among non‐obese individuals. This is the first investigation having observed/found genetic variations on genetic loci functionally linked with glycosylation associated with the risk of T2DM in a Uyghur population. 相似文献
10.
Luisa Gennero Maria Augusta Roos Patrizia D'Amelio Tetyana Denysenko Emanuella Morra Kirk Sperber Vincenzo Ceroni Michele Panzone Franco Lesca Enrico De Vivo Anastasia Grimaldi Maria Luisa Gabetti Antonio Ponzetto Gian Piero Pescarmona Agostino Pugliese 《Cell biochemistry and function》2010,28(2):142-148
Different haptoglobin (Hp) phenotypes play a role in several pathologic processes including infectious diseases. In order to evaluate the role of iron storage and metabolism in susceptibility to herpetic manifestations, we studied the frequency of the Hp phenotypes and iron metabolism in patients affected by H. Simplex virus 1 or 2 (HSV‐1 or HSV‐2), compared with controls. Hp phenotype and iron metabolism were determined in 100 patients with recurrent HSV‐1 or HSV‐2 manifestations during the relapses, and in 110 healthy subjects. The frequencies of the three Hp phenotypes in the patient group compared to the control group were 18% versus 14.5% p = NS for Hp 1.1, 25% versus 40% p = 0.03 for Hp 2.2 and 57% versus 45.5% p = NS for Hp 2.1. All iron metabolism parameters tested showed significant differences between patients and controls; haemoglobin (Hb), ferritin, and serum iron were lower, while transferrin was higher in the patients than in controls. Reductions in iron availability may be a risk factor for relapsing lesions of HSV‐1 or HSV‐2. Hp 2.2 phenotype may offer some protection against the recurrence of Herpes labialis or genitalis manifestations. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
11.
The reproductive factor (R = final egg density at 55 days ÷ 5,000, initial egg density) of Meloidogyne chitwoodi race 2 (alfalfa race) on 46 crop cultivars ranged from 0 to 130. The reproductive efficiency of M. chitwoodi race 1 (non-alfalfa race) and M. chitwoodi race 2 was compared on selected crop cultivars. The basic difference between the two races lay in their differential reproduction on Thor alfalfa and Red Cored Chantenay carrot. M. chitwoodi race 2 reproduced on alfalfa but not on carrot. Conversely, alfalfa was a poor host and carrots were suitable for M. chitwoodi race 1. Based on host responses to M. chitwoodi races and M. hapla, a new differential host test was proposed to distinguish the common root-knot nematode species of the Pacific Northwest. 相似文献
12.
Coagulase-negative staphylococci, particularly Staphylococcusepidermidis, can be regarded as potential reservoirs of resistance genesfor pathogenic strains, e.g., Staphylococcus aureus. The aim of thisstudy was to assess the prevalence of different resistance phenotypes to macrolide,lincosamide, and streptogramins B (MLSB) antibiotics among erythromycin-resistantS. epidermidis, together with the evaluation of genes promotingthe following different types of MLSB resistance:ermA,ermB, ermC,msrA,mphC, and linA/A’. Susceptibility to spiramycinwas also examined. Among 75 erythromycin-resistantS. epidermidisisolates, the most frequent phenotypes were macrolides and streptogramins B (MSB) andconstitutive MLSB (cMLSB). Moreover, all strains with the cMLSB phenotype and themajority of inducible MLSB (iMLSB) isolates were resistant to spiramycin, whereasstrains with the MSB phenotype were sensitive to this antibiotic. The D-shape zone ofinhibition around the clindamycin disc near the spiramycin disc was found for somespiramycin-resistant strains with the iMLSB phenotype, suggesting an induction ofresistance to clindamycin by this 16-membered macrolide. The most frequently isolatedgene was ermC, irrespective of the MLSB resistance phenotype,whereas the most often noted gene combination wasermC,mphC, linA/A’. The results obtained showed thatthe genes responsible for different mechanisms of MLSB resistance in S.epidermidis generally coexist, often without the phenotypic expression ofeach of them. 相似文献
13.
The role of hydroxyl radical (.OH) damaged human serum albumin (HSA) in type 1 diabetes has been investigated in the present study. Hydroxyl radical induced modification on HSA has been studied by UV absorption spectroscopy, ANS fluorescence and carbonyl estimation. Hydroxyl radical modified HSA was found to be highly immunogenic in rabbits as compared to native HSA. The binding characteristics of circulating autoantibodies in type 1 diabetes patients against native and modified HSA were assessed. Diabetes patients (n=31) were examined by direct binding ELISA and the results were compared with healthy age-matched controls (n=22). High degree of specific binding by 54.8% of patients sera towards .OH modified HSA, in comparison to its native analogue (p<0.05) was observed. Sera from those type 1 diabetes patients having smoking history, high aging with high degree of disease showed substantially stronger binding to .OH modified HSA over native HSA in particular. Normal human sera showed negligible binding with either antigen. Competitive inhibition ELISA reiterates the direct binding results. Gel retardation assay further substantiated the enhanced recognition of modified HSA by circulating autoantibodies in diabetes patients. The increase in total serum protein carbonyl levels in the diabetes patients was largely due to an increase in oxidized albumin. HSA of diabetes mellitus patients (DM-HSA) and normal subjects (normal-HSA) were purified on a Sephacryl S-200 HR column. Spectroscopic analysis confirmed that the DM-HSA samples contained higher levels of carbonyls than normal-HSA (p<0.001). DM-HSA was conformationally altered, with more exposure of its hydrophobic regions. Collectively, the oxidation of plasma proteins, especially HSA, might enhance oxidative stress in type 1 diabetes mellitus patients. 相似文献
14.
Capoluongo E Pitocco D Lulli P Minucci A Santonocito C Manto A Di Stasio E Zaccardi F Zuppi C Ghirlanda G Ameglio F 《Cytokine》2006,34(5-6):303-311
BACKGROUND: Even though the gene encoding for IGF-I is considered of most importance amongst blood pressure-regulating genes in mouse models, little and discordant data are available in literature for what concerns a possible relationship between blood pressure and serum free IGF-I values in humans. In addition, no information is available on type 1 diabetes patients. AIM: Our aim is to analyze the relationship between systolic and diastolic blood pressure and serum free IGF-I and IGFBP-3 levels in subjects suffering from type 1 diabetes. RESULTS: A highly significant inverse correlation was observed between serum free IGF-I levels and both systolic and diastolic blood pressure in subjects affected with type 1 diabetes. Similar but less significant relationships were observed for IGFBP-3, whose levels were also significantly and directly correlated with those of free IGF-I. The correlation between systolic and diastolic blood pressures with free IGF-I and between systolic blood pressure and IGFBP-3 levels were confirmed after adjusting for age, gender, age at diagnosis, disease duration, familial history, HBA1c, and amount of insulin administered by multivariate logistic regression analysis. A decrease in free IGF-I and IGFBP-3 levels, along with increases in blood pressure, significantly influenced the presence of diabetic complications, confirming how these molecules may be considered as severity markers for patients with type 1 diabetes as well as risk factors for altered pressure control linked diseases. 相似文献
15.
PD‐L1 expression in melanoma shows marked heterogeneity within and between patients: implications for anti‐PD‐1/PD‐L1 clinical trials 下载免费PDF全文
Jason Madore Ricardo E. Vilain Alexander M. Menzies Hojabr Kakavand James S. Wilmott Jessica Hyman Jennifer H. Yearley Richard F. Kefford John F. Thompson Georgina V. Long Peter Hersey Richard A. Scolyer 《Pigment cell & melanoma research》2015,28(3):245-253
This study evaluated the expression of PD‐L1 in immunotherapy‐naïve metastatic melanoma patients to determine longitudinal intrapatient concordance and correlate PD‐L1 status with clinicopathologic characteristics and outcome. PD‐L1 expression was assessed by immunohistochemistry in 58 patients (43 primary tumors, 96 metastases). Seventy‐two percent of patients had at least one specimen expressing PD‐L1 in ≥1% of tumor cells. Median positive tumor cell count overall was low (8% in nonzero specimens). PD‐L1 expression was frequently discordant between primary tumors and metastases and between intrapatient metastases, such that 23/46 longitudinal patient specimens were discordant. PD‐L1 was associated with higher TIL grade but not with other known prognostic features. There was a positive univariate association between PD‐L1 expression in locoregional metastases and melanoma‐specific survival, but the effect was not observed for primary melanoma. In locoregional lymph node metastasis, PD‐L1+/TIL+ patients had the best outcome, and PD‐L1+/TIL? patients had poor outcome. 相似文献
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Matteo Zurlo Francesco Nicoli Davide Proietto Beatrice Dallan Cristina Zuccato Lucia Carmela Cosenza Jessica Gasparello Chiara Papi Elisabetta d'Aversa Monica Borgatti Chiara Scapoli Alessia Finotti Roberto Gambari 《Journal of cellular and molecular medicine》2023,27(3):353
Inhibitors of the mammalian target of rapamycin (mTOR) have been proposed to improve vaccine responses, especially in the elderly. Accordingly, testing mTOR inhibitors (such as Sirolimus) and other geroprotective drugs might be considered a key strategy to improve overall health resilience of aged populations. In this respect, Sirolimus (also known as rapamycin) is of great interest, in consideration of the fact that it is extensively used in routine therapy and in clinical studies for the treatment of several diseases. Recently, Sirolimus has been considered in laboratory and clinical studies aimed to find novel protocols for the therapy of hemoglobinopathies (e.g. β‐Thalassemia). The objective of the present study was to analyse the activity of CD4+ and CD8+ T cells in β‐Thalassemia patients treated with Sirolimus, taking advantages from the availability of cellular samples of the clinical trial. The approach was to verify IFN‐γ releases following stimulation of peripheral blood mononuclear cells (PBMCs) to stimulatory CEF and CEFTA peptide pools, stimulatory for CD4+ and CD8+ T cells, respectively. The main results of the present study are that treatment of β‐Thalassemia patients with Sirolimus has a positive impact on the biological activity and number of memory CD4+ and CD8+ T cells releasing IFN‐γ following stimulation with antigenic stimuli present in immunological memory. These data are to our knowledge novel and in our opinion of interest, in consideration of the fact that β‐Thalassemia patients are considered prone to immune deficiency. NCT03877809相似文献
18.
Penghui Wang Yiqing Pan Chenghao Yang Linjie Zhang Zhen Zhao Kaichuang Ye Lei Li Shoubing Xia Xinwu Lu Huihua Shi Weimin Li Minyi Yin 《Journal of cellular and molecular medicine》2022,26(16):4479
Venous calcification has been observed in post‐thrombotic syndrome (PTS) patients; yet, the cell types and possible mechanisms regulating this process are still unclear. We evaluated the calcium deposition within the venous wall, the cell type involved in the calcified remodelling of the venous wall after thrombosis and explored possible mechanisms in vitro. Calcium deposition was found in human specimens of superficial thrombotic veins and was co‐localized with VSMCs markers αSMA and TAGLN (also known as SM22α). Besides, the expression of osteogenesis‐related genes was dramatically changed in superficial thrombotic veins. Moreover, the inhibition of the TGFβ signalling pathway after TNFα treatment effectively induced the expression of osteogenic phenotype markers, the calcium salt deposits and the obvious phosphorylation of ERK1/2 and JNK2 in the VSMCs calcification model. Supplementing TGFβ2 or blocking the activation of the ERK/MAPK signalling pathway prevented the transformation of VSMCs into osteoblast‐like cells in vitro. Taken together, VSMCs have an important role in venous calcification after thrombosis. Supplementing TGFβ2 or inhibiting the ERK/MAPK signalling pathway can reduce the appearance of VSMCs osteogenic phenotype. Our findings may present a novel therapeutic approach to prevent of vascular calcification after venous thrombosis. 相似文献
19.
Emmanuelle Feuvrier Magali Aubert Anne-Laure Mausset Gérard Alonso Sylvie Gaillet Francis Malaval Alain Szafarczyk 《Journal of neurochemistry》1998,70(3):1199-1209
Abstract: We have shown previously that noradrenaline (NA) stimulated or inhibited the release of corticotropin-releasing hormone (CRH) according to the availability of adrenal steroids. The aim of the present work was to examine whether the changes in the NA modulation of CRH release from hypothalamic neurons result from a steroid-induced plasticity of the adrenergic transduction pathways. From anterior hypothalamic slices cultured in standard medium (i.e., containing adrenal steroids at a final dilution of 61 ± 9 ng/ml), (a) the stimulatory effect of NA on CRH release was reversed in a dose-dependent manner by increasing concentrations of the α1 -adrenoreceptor antagonist prazosin, (b) activation of protein kinase C by acute treatment with phorbol 12-myristate 13-acetate (0.5 µ M , 1 h) mimicked NA stimulation of CRH secretion, and (c) the activation of L-type Ca2+ channels by Bay K 8644 also produce an increased CRH secretion. In contrast, the inhibitory effect of NA on CRH secretion from slices cultured in steroid-free medium was markedly reversed by the α2 -adrenoreceptor antagonist yohimbine, by pretreatment with pertussin toxin, or by the addition of 4-aminopyridine, a K+ -channel blocker. Acute treatment with phorbol 12-myristate 13-acetate did not change the inhibitory NA effect. Moreover, all these effects were reversed by daily corticosterone supplementation, for as long as they were tested. These results are consistent with a steroid-dependent change in the nature of adrenergic receptors and its associated transduction pathways involved in the regulation of CRH secretion in the hypothalamus. 相似文献
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Summary. Described is an alternative procedure for the phenotyping of pig α1 B-glycoprotein (PO2) and haemopexin. The procedure is based on the separation of serum samples by horizontal polyacrylamide gel electrophoresis, passive blotting onto a nitrocellulose (NC) sheet, and immunochemical detection using a mixture of a primary antibody (rabbit anti-pig α1 B or anti-pig haemopexin) and a peroxidase-labelled secondary antibody. Several NC copies can be obtained from a single gel and these can be developed with different monospecific antisera. 相似文献