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1.
Letícia Helena dos Santos Marques Luciana Inácia Gomes Iara Caixeta Marques da Rocha Thaís Almeida Marques da Silva Edward Oliveira Maria Helena Franco Morais Ana Rabello Mariangela Carneiro 《PLoS neglected tropical diseases》2012,6(12)
Background
An important issue associated with the control of visceral leishmaniasis is the need to identify and understand the relevance of asymptomatic infection caused by Leishmania infantum. The aim of this study was to follow the course of asymptomatic L. infantum infection in children in an area of Brazil where it is endemic. The children were assessed twice during a 12-month period.Methodology
In this population study, 1875 children, ranging from 6 months to 7 years of age, were assessed. Blood samples were collected on filter papers via finger prick and tested by ELISA (L. infantum soluble antigen and rk39). Seropositives samples (n = 317) and a number of seronegatives samples (n = 242) were subjected to qPCR. After 12 months, blood samples were collected from a subgroup of 199 children and tested for Leishmania spp. to follow the course of infection.Principal Findings
At baseline qPCR testing identified 82 positive samples. The prevalence rate, as estimated for 1875 children based on the qPCR results, was 13.9%. The qPCR testing of whole blood samples collected from a cohort of children after 12 months (n = 199) yielded the following results: of the 44 (22.1%) children with positive qPCR results at baseline, only 10 (5.0%) remained positive, and 34 (17.1%) became negative; and of the 155 (77.9%) children with negative qPCR results, 131 (65.8%) remained negative, and 24 (12.1%) became positive at the follow-up measurement. The samples with positive findings at baseline (n = 82) had a mean of 56.5 parasites/mL of blood; and at follow-up the mean positive result was 7.8 parasites/mL.Conclusions
The peripheral blood of asymptomatic children had a low and fluctuating quantity of Leishmania DNA and a significant decrease in parasitemia at 1-year follow-up. Quantitative PCR enables adequate monitoring of Leishmania infection. 相似文献2.
Guerra JA Prestes SR Silveira H Coelho LI Gama P Moura A Amato V Barbosa Md Ferreira LC 《PLoS neglected tropical diseases》2011,5(3):e980
Background
Leishmania (Viannia) braziliensis is a parasite recognized as the most important etiologic agent of mucosal leishmaniasis (ML) in the New World. In Amazonia, seven different species of Leishmania, etiologic agents of human Cutaneous Leishmaniasis, have been described. Isolated cases of ML have been described for several different species of Leishmania: L. (V.) panamensis, L. (V.) guyanensis and L. (L.) amazonensis.Methodology
Leishmania species were characterized by polymerase chain reaction (PCR) of tissues taken from mucosal biopsies of Amazonian patients who were diagnosed with ML and treated at the Tropical Medicine Foundation of Amazonas (FMTAM) in Manaus, Amazonas state, Brazil. Samples were obtained retrospectively from the pathology laboratory and prospectively from patients attending the aforementioned tertiary care unit.Results
This study reports 46 cases of ML along with their geographical origin, 30 cases caused by L. (V.) braziliensis and 16 cases by L. (V.) guyanensis. This is the first record of ML cases in 16 different municipalities in the state of Amazonas and of simultaneous detection of both species in 4 municipalities of this state. It is also the first record of ML caused by L. (V.) guyanensis in the states of Pará, Acre, and Rondônia and cases of ML caused by L. (V.) braziliensis in the state of Rondônia.Conclusions/Significance
L. (V.) braziliensis is the predominant species that causes ML in the Amazon region. However, contrary to previous studies, L. (V.) guyanensis is also a significant causative agent of ML within the region. The clinical and epidemiological expression of ML in the Manaus region is similar to the rest of the country, although the majority of ML cases are found south of the Amazon River.Author Summary
Leishmaniasis is considered a neglected disease with 1.5 million new cases of cutaneous leishmaniasis (CL) occurring each year. In the Amazon region and in the Americas in general, ML is caused by Leishmania (Viannia) braziliensis, though in rare cases it has been related to other species. ML, which is associated with inadequate treatment of CL, normally manifests itself years after the occurrence of CL. Clinical features evolve slowly and most often affect the nasal cavity, in some cases causing perforation, or even destruction, of the septum. Diagnosis is made using the Montenegro skin test, serology and histopathology of the patients'' mucosal tissues, or by isolation of the parasites. PCR is the best way to identify the species of leishmaniasis and is therefore the diagnostic method of choice. This paper describes 46 cases of ML and their geographical origin, 30 cases associated with L. (V.) braziliensis and 16 with L. (V.) guyanensis. The species of leishmaniasis was identified using mucosal biopsies taken from Amazonian patients who were diagnosed and treated for ML in the tertiary care unit, in Manaus, Amazonas state, Brazil. This is the highest number of ML cases caused by L. (V.) guyanensis that has ever been reported. 相似文献3.
Om Prakash Singh Carmel B. Stober Abhishek Kr. Singh Jenefer M. Blackwell Shyam Sundar 《PLoS neglected tropical diseases》2012,6(10)
Background
There are no effective vaccines for visceral leishmaniasis (VL), a neglected parasitic disease second only to malaria in global mortality. We previously identified 14 protective candidates in a screen of 100 Leishmania antigens as DNA vaccines in mice. Here we employ whole blood assays to evaluate human cytokine responses to 11 of these antigens, in comparison to known defined and crude antigen preparations.Methods
Whole blood assays were employed to measure IFN-γ, TNF-α and IL-10 responses to peptide pools of the novel antigens R71, Q51, L37, N52, L302.06, J89, M18, J41, M22, M63, M57, as well as to recombinant proteins of tryparedoxin peroxidase (TRYP), Leishmania homolog of the receptor for activated C kinase (LACK) and to crude soluble Leishmania antigen (SLA), in Indian patients with active (n = 8) or cured (n = 16) VL, and in modified Quantiferon positive (EHC+ve, n = 20) or modified Quantiferon negative (EHC−ve, n = 9) endemic healthy controls (EHC).Results
Active VL, cured VL and EHC+ve groups showed elevated SLA-specific IFN-γ, but only active VL patients produced IL-10 and EHC+ve did not make TNF-α. IFN-γ to IL-10 and TNF-α to IL-10 ratios in response to TRYP and LACK antigens were higher in cured VL and EHC+ve exposed individuals compared to active VL. Five of the eleven novel candidates (R71, L37, N52, J41, and M22) elicited IFN-γ and TNF-α, but not IL-10, responses in cured VL (55–87.5% responders) and EHC+ve (40–65% responders) subjects.Conclusions
Our results are consistent with an important balance between pro-inflammatory IFNγ and TNFγ cytokine responses and anti-inflammatory IL-10 in determining outcome of VL in India, as highlighted by response to both crude and defined protein antigens. Importantly, cured VL patients and endemic Quantiferon positive individuals recognise 5 novel vaccine candidate antigens, confirming our recent data for L. chagasi in Brazil, and their potential as cross-species vaccine candidates. 相似文献4.
Rodrigo Almeida-Paes Manoel Marques Evangelista de Oliveira Dayvison Francis Saraiva Freitas Ant?nio Carlos Francesconi do Valle Rosely Maria Zancopé-Oliveira Maria Clara Gutierrez-Galhardo 《PLoS neglected tropical diseases》2014,8(9)
Background
There have been several recent changes in the taxonomy of Sporothrix schenckii as well as new observations regarding the clinical aspects of sporotrichosis. In this study, we determined the identification of the Sporothrix species associated with both classic and unusual clinical aspects of sporotrichosis observed in the endemic area of sporotrichosis in Rio de Janeiro, Brazil.Methodology/Principal Findings
To verify whether S. brasiliensis is associated with clinical manifestations of sporotrichosis, a cross-sectional study was performed in which Sporothrix isolates from 50 patients with different clinical manifestations were analyzed and their isolates were studied by phenotypic and genotypic methods. Data from these patients revealed a distinct clinical picture and therapeutic response in infections caused by Sporothrix brasiliensis (n = 45) compared to patients with S. schenckii sensu stricto (n = 5). S. brasiliensis was associated with disseminated cutaneous infection without underlying disease, hypersensitivity reactions, and mucosal infection, whereas patients with S. schenckii presented with less severe and more often localized disease, similar to the majority of previously described sporotrichosis cases. Interestingly, S. brasiliensis-infected patients overall required shorter durations of itraconazole (median 16 weeks) compared to the individuals with S. schenckii (median 24 weeks).Conclusions/Significance
These findings suggest that Sporothrix species are linked to different clinical manifestations of sporotrichosis and that S. brasiliensis is effectively treated with oral itraconazole. 相似文献5.
Background
The etiology of birth defects has been widely studied but is not yet fully clarified, previously published data had suggested that maternal age or parity maybe involved, but without consistent conclusions.Methods
A population-based, case-control study was nested in a cohort of perinatal infants born from 2010 to 2012 in Baoan District, Shenzhen. Four categories of isolated birth defects were defined as cases: congenital heart defects (CHD, n = 693), polydactyly (n = 352), cleft lip with or without palate (CL/P, n = 159) and equinovarus (n = 119). Controls were non-malformed infants (n = 11,307) randomly selected from the same area and period. Odds ratios (ORs) and the 95% confidence intervals (CIs) were computed by multivariable unconditional logistic regression analysis.Results
Young maternal age (<25 years old) was associated with a reduced risk of CHD (adjusted OR = 0.73, 95% CI 0.59–0.90), while with an elevated risk of polydactyly (adjusted OR = 1.42, 95% CI 1.09-1.84). Increased risk of CL/P-affected pregnancy was observed in mothers older than 35 years old (adjusted OR = 2.12, 95% CI 1.26–3.57). Compared to primipara, those having their second, and third or more delivery were less likely to have infants with equinovarus, with significant adjusted ORs of 0.59 (0.40–0.89) and 0.42 (0.19–0.93), respectively.Conclusion
Maternal age was significantly associated with CHD, polydactyly and CL/P relevant pregnancy. Mothers with higher parity might have lower risk of equinovarus occurrence in offsprings. 相似文献6.
Mohammed A. K. Mahdy Hesham M. Al-Mekhlafi Abdulsalam M. Al-Mekhlafi Yvonne A. L. Lim Naemah O. M. Bin Shuaib Ahmed A. Azazy Rohela Mahmud 《PloS one》2010,5(9)
Background
Cutaneous leishmaniasis (CL) is a neglected tropical disease endemic in the tropics and subtropics with a global yearly incidence of 1.5 million. Although CL is the most common form of leishmaniasis, which is responsible for 60% of DALYs lost due to tropical-cluster diseases prevalent in Yemen, available information is very limited.Methodology/Principal Findings
This study was conducted to determine the molecular characterization of Leishmania species isolated from human cutaneous lesions in Yemen. Dermal scrapes were collected and examined for Leishmania amastigotes using the Giemsa staining technique. Amplification of the ribosomal internal transcribed spacer 1(ITS-1) gene was carried out using nested PCR and subsequent sequencing. The sequences from Leishmania isolates were subjected to phylogenetic analysis using the neighbor-joining and maximum parsimony methods. The trees identified Leishmania tropica from 16 isolates which were represented by two sequence types.Conclusions/Significance
The predominance of the anthroponotic species (i.e. L. tropica) indicates the probability of anthroponotic transmission of cutaneous leishmaniasis in Yemen. These findings will help public health authorities to build an effective control strategy taking into consideration person–to-person transmission as the main dynamic of transmission of CL. 相似文献7.
Nageswara Rao Tipirisetti Suresh Govatati Priyanka Pullari Sravanthi Malempati Murali Krishna Thupurani Shyam Perugu Praveen Guruvaiah Lakshmi Rao K Raghunadha Rao Digumarti Varadacharyulu Nallanchakravarthula Manjula Bhanoori Vishnupriya Satti 《PloS one》2014,9(1)
Background
Mitochondrial displacement loop (D-loop) is the hot spot for mitochondrial DNA (mtDNA) alterations which influence the generation of cellular reactive oxygen species (ROS). Association of D-loop alterations with breast cancer has been reported in few ethnic groups; however none of the reports were documented from Indian subcontinent.Methodology
We screened the entire mitochondrial D-loop region (1124 bp) of breast cancer patients (n = 213) and controls (n = 207) of south Indian origin by PCR-sequencing analysis. Haplotype frequencies for significant loci, the standardized disequilibrium coefficient (D′) for pair-wise linkage disequilibrium (LD) were assessed by Haploview Software.Principal Findings
We identified 7 novel mutations and 170 reported polymorphisms in the D-loop region of patients and/or controls. Polymorphisms were predominantly located in hypervariable region I (60%) than in II (30%) of D-loop region. The frequencies of 310‘C’ insertion (P = 0.018), T16189C (P = 0.0019) variants and 310‘C’ins/16189C (P = 0.00019) haplotype were significantly higher in cases than in controls. Furthermore, strong LD was observed between nucleotide position 310 and 16189 in controls (D′ = 0.49) as compared to patients (D′ = 0.14).Conclusions
Mitochondrial D-loop alterations may constitute inherent risk factors for breast cancer development. The analysis of genetic alterations in the D-loop region might help to identify patients at high risk for bad progression, thereby helping to refine therapeutic decisions in breast cancer. 相似文献8.
Onkar Singh Jason Yongsheng Chan Keegan Lin Charles Chuah Thuan Heng Balram Chowbay 《PloS one》2012,7(12)
Objective
This study aimed to explore the influence of SLC22A1, PXR, ABCG2, ABCB1 and CYP3A5*3 genetic polymorphisms on imatinib mesylate (IM) pharmacokinetics in Asian patients with chronic myeloid leukemia (CML).Patients and Methods
Healthy subjects belonging to three Asian populations (Chinese, Malay, Indian; n = 70 each) and CML patients (n = 38) were enrolled in a prospective pharmacogenetics study. Imatinib trough (C0h) and clearance (CL) were determined in the patients at steady state. Haplowalk method was applied to infer the haplotypes and generalized linear model (GLM) to estimate haplotypic effects on IM pharmacokinetics. Association of haplotype copy numbers with IM pharmacokinetics was defined by Mann-Whitney U test.Results
Global haplotype score statistics revealed a SLC22A1 sub-haplotypic region encompassing three polymorphisms (rs3798168, rs628031 and IVS7+850C>T), to be significantly associated with IM clearance (p = 0.013). Haplotype-specific GLM estimated that the haplotypes AGT and CGC were both associated with 22% decrease in clearance compared to CAC [CL (*10−2 L/hr/mg): CAC vs AGT: 4.03 vs 3.16, p = 0.017; CAC vs CGC: 4.03 vs 3.15, p = 0.017]. Patients harboring 2 copies of AGT or CGC haplotypes had 33.4% lower clearance and 50% higher C0h than patients carrying 0 or 1 copy [CL (*10−2 L/hr/mg): 2.19 vs 3.29, p = 0.026; C0h (*10−6 1/ml): 4.76 vs 3.17, p = 0.013, respectively]. Further subgroup analysis revealed SLC22A1 and ABCB1 haplotypic combinations to be significantly associated with clearance and C0h (p = 0.002 and 0.009, respectively).Conclusion
This exploratory study suggests that SLC22A1-ABCB1 haplotypes may influence IM pharmacokinetics in Asian CML patients. 相似文献9.
de Moura TR Oliveira F Novais FO Miranda JC Clarêncio J Follador I Carvalho EM Valenzuela JG Barral-Netto M Barral A Brodskyn C de Oliveira CI 《PLoS neglected tropical diseases》2007,1(2):e84
Background
Sand fly saliva has an array of pharmacological and immunomodulatory components, and immunity to saliva protects against Leishmania infection. In the present study, we have studied the immune response against Lutzomyia intermedia saliva, the main vector of Leishmania braziliensis in Brazil, and the effects of saliva pre-exposure on L. braziliensis infection employing an intradermal experimental model.Methodology/principal findings
BALB/c mice immunized with L. intermedia salivary gland sonicate (SGS) developed a saliva-specific antibody response and a cellular immune response with presence of both IFN-γ and IL-4. The inflammatory infiltrate observed in SGS-immunized mice was comprised of numerous polymorphonuclear and few mononuclear cells. Mice challenged with live L. braziliensis in the presence of saliva were not protected although lesion development was delayed. The inoculation site and draining lymph node showed continuous parasite replication and low IFN-γ to IL-4 ratio, indicating that pre-exposure to L. intermedia saliva leads to modulation of the immune response. Furthermore, in an endemic area of cutaneous leishmaniasis, patients with active lesions displayed higher levels of anti-L. intermedia saliva antibodies when compared to individuals with a positive skin test result for Leishmania.Conclusion
These results show that pre-exposure to sand fly saliva plays an important role in the outcome of cutaneous leishmaniasis, in both mice and humans. They emphasize possible hurdles in the development of vaccines based on sand fly saliva and the need to identify and select the individual salivary candidates instead of using whole salivary mixture that may favor a non-protective response. 相似文献10.
11.
Gilad Horowitz Moran Amit Oded Ben-Ari Ziv Gil Abraham Abergel Nevo Margalit Oren Cavel Oshri Wasserzug Dan M. Fliss 《PloS one》2013,8(12)
Objective
To compare frontal sinus cranialization to obliteration for future prevention of secondary mucocele formation following open surgery for benign lesions of the frontal sinus.Study Design
Retrospective case series.Setting
Tertiary academic medical center.Patients
Sixty-nine patients operated for benign frontal sinus pathology between 1994 and 2011.Interventions
Open excision of benign frontal sinus pathology followed by either frontal obliteration (n = 41, 59%) or frontal cranialization (n = 28, 41%).Main Outcome Measures
The prevalence of post-surgical complications and secondary mucocele formation were compiled.Results
Pathologies included osteoma (n = 34, 49%), mucocele (n = 27, 39%), fibrous dysplasia (n = 6, 9%), and encephalocele (n = 2, 3%). Complications included skin infections (n = 6), postoperative cutaneous fistula (n = 1), telecanthus (n = 4), diplopia (n = 3), nasal deformity (n = 2) and epiphora (n = 1). None of the patients suffered from postoperative CSF leak, meningitis or pneumocephalus. Six patients, all of whom had previously undergone frontal sinus obliteration, required revision surgery due to secondary mucocele formation. Statistical analysis using non-inferiority test reveal that cranialization of the frontal sinus is non-inferior to obliteration for preventing secondary mucocele formation (P<0.0001).Conclusion
Cranialization of the frontal sinus appears to be a good option for prevention of secondary mucocele development after open excision of benign frontal sinus lesions. 相似文献12.
13.
Machado PR Ampuero J Guimarães LH Villasboas L Rocha AT Schriefer A Sousa RS Talhari A Penna G Carvalho EM 《PLoS neglected tropical diseases》2010,4(12):e912
Background
Cutaneous leishmaniasis (CL) is treated with parenteral drugs for decades with decreasing rate cures. Miltefosine is an oral medication with anti-leishmania activity and may increase the cure rates and improve compliance.Methodology/Principal Findings
This study is a randomized, open-label, controlled clinical trial aimed to evaluate the efficacy and safety of miltefosine versus pentavalent antimony (Sbv) in the treatment of patients with CL caused by Leishmania braziliensis in Bahia, Brazil. A total of 90 patients were enrolled in the trial; 60 were assigned to receive miltefosine and 30 to receive Sbv. Six months after treatment, in the intention-to-treat analyses, the definitive cure rate was 53.3% in the Sbv group and 75% in the miltefosine group (difference of 21.7%, 95% CI 0.08% to 42.7%, p = 0.04). Miltefosine was more effective than Sbv in the age group of 13–65 years-old compared to 2–12 years-old group (78.9% versus 45% p = 0.02; 68.2% versus 70% p = 1.0, respectively). The incidence of adverse events was similar in the Sbv and miltefosine groups (76.7% vs. 78.3%). Vomiting (41.7%), nausea (40%), and abdominal pain (23.3%) were significantly more frequent in the miltefosine group while arthralgias (20.7%), mialgias (20.7%) and fever (23.3%) were significantly more frequent in the Sbv group.Conclusions
This study demonstrates that miltefosine therapy is more effective than standard Sbv and safe for the treatment of CL caused by Leishmania braziliensis in Bahia, Brazil.Trial Registration
Clinicaltrials.gov Identifier NCT00600548相似文献14.
Purpose
A recent large genome-wide association study (GWAS) identified multiple variants associated with primary angle-closure glaucoma (PACG). The present study investigated the role of these variants in two cohorts with PACG recruited from Australia and Nepal.Method
Patients with PACG and appropriate controls were recruited from eye clinics in Australia (n = 232 cases and n = 288 controls) and Nepal (n = 106 cases and 204 controls). Single nucleotide polymorphisms (SNPs) rs3753841 (COL11A1), rs1015213 (located between PCMTD1 and ST18), rs11024102 (PLEKHA7), and rs3788317 (TXNRD2) were selected and genotyped on the Sequenom. Analyses were conducted using PLINK and METAL.Results
After adjustment for age and sex, SNP rs3753841 was found to be significantly associated with PACG in the Australian cohort (p = 0.017; OR = 1.34). SNPs rs1015213 (p = 0.014; OR 2.35) and rs11024102 (p = 0.039; OR 1.43) were significantly associated with the disease development in the Nepalese cohort. None of these SNPs survived Bonferroni correction (p = 0.05/4 = 0.013). However, in the combined analysis, of both cohorts, rs3753841 and rs1015213 showed significant association with p-values of 0.009 and 0.004, respectively both surviving Bonferroni correction. SNP rs11024102 showed suggestive association with PACG (p-value 0.035) and no association was found with rs3788317.Conclusion
The present results support the initial GWAS findings, and confirm the SNP’s contribution to PACG. This is the first study to investigate these loci in both Australian Caucasian and Nepalese populations. 相似文献15.
Louise K. Sj?holm Lena Backlund Emarndeena Haji Cheteh Inger R?mer Ek Louise Frisén Martin Schalling Urban ?sby Catharina Lavebratt Pernilla Nikamo 《PloS one》2010,5(9)
Background
Bipolar disorder patients often display abnormalities in circadian rhythm, and they are sensitive to irregular diurnal rhythms. CRY2 participates in the core clock that generates circadian rhythms. CRY2 mRNA expression in blood mononuclear cells was recently shown to display a marked diurnal variation and to respond to total sleep deprivation in healthy human volunteers. It was also shown that bipolar patients in a depressive state had lower CRY2 mRNA levels, nonresponsive to total sleep deprivation, compared to healthy controls, and that CRY2 gene variation was associated with winter depression in both Swedish and Finnish cohorts.Principal Findings
Four CRY2 SNPs spanning from intron 2 to downstream 3′UTR were analyzed for association to bipolar disorder type 1 (n = 497), bipolar disorder type 2 (n = 60) and bipolar disorder with the feature rapid cycling (n = 155) versus blood donors (n = 1044) in Sweden. Also, the rapid cycling cases were compared with bipolar disorder cases without rapid cycling (n = 422). The haplotype GGAC was underrepresented among rapid cycling cases versus controls and versus bipolar disorder cases without rapid cycling (OR = 0.7, P = 0.006−0.02), whereas overrepresentation among rapid cycling cases was seen for AAAC (OR = 1.3−1.4, P = 0.03−0.04) and AGGA (OR = 1.5, P = 0.05). The risk and protective CRY2 haplotypes and their effect sizes were similar to those recently suggested to be associated with winter depression in Swedes.Conclusions
We propose that the circadian gene CRY2 is associated with rapid cycling in bipolar disorder. This is the first time a clock gene is implicated in rapid cycling, and one of few findings showing a molecular discrimination between rapid cycling and other forms of bipolar disorder. 相似文献16.
Daniel Schnorr Aline C. Muniz Sara Passos Luiz H. Guimaraes Ednaldo L. Lago Olívia Bacellar Marshall J. Glesby Edgar M. Carvalho 《PLoS neglected tropical diseases》2012,6(12)
Background
Cutaneous leishmaniasis due to L. braziliensis (CL) is characterized by a positive delayed type hypersensitivity test (DTH) leishmania skin test (LST) and high IFN-γ production to soluble leishmania antigen (SLA). The LST is used for diagnosis of CL and for identification of individuals exposed to leishmania infection but without disease. The main aim of the present study was to identify markers of exposure to L. braziliensis infection.Methodolgy/Principal Findings
This cohort study enrolled 308 household contacts (HC) of 76 CL index cases. HC had no active or past history of leishmaniasis. For the present cross-sectional study cytokines and chemokines were determined in supernatants of whole blood culture stimulated with SLA. Of the 308 HC, 36 (11.7%) had a positive LST but in these IFN-γ was only detected in 22 (61.1%). Moreover of the 40 HC with evidence of IFN-γ production only 22 (55%) had a positive LST. A total of 54 (17.5%) of 308 HC had specific immune response to SLA. Only a moderate agreement (Kappa = 0.52; 95% CI: 0.36–0.66) was found between LST and IFN-γ production. Moreover while enhancement of CXCL10 in cultures stimulated with SLA was observed in HC with DTH+ and IFN-γ+ and in patients with IFN-γ+ and DTH−, no enhancement of this chemokine was observed in supernatants of cells of HC with DTH+ and IFN-γ−.Conclusions/Significance
This study shows that in addition of LST, the evaluation of antigen specific IFN-γ production should be performed to determine evidence of exposure to leishmania infection. Moreover it suggests that in some HC production of IFN-γ and CXCL10 are performed by cells not involved with DTH reaction. 相似文献17.
Dulciene Maria Magalhaes Queiroz Paul R. Harris Ian R. Sanderson Henry J. Windle Marjorie M. Walker Andreia Maria Camargos Rocha Gifone Aguiar Rocha Simone Diniz Carvalho Paulo Fernando Souto Bittencourt Lucia Porto Fonseca de Castro Andrea Villagrán Carolina Serrano Dermot Kelleher Jean E. Crabtree 《PloS one》2013,8(7)
Objective
Iron deficiency (ID) and iron deficiency anaemia (IDA) are global major public health problems, particularly in developing countries. Whilst an association between H. pylori infection and ID/IDA has been proposed in the literature, currently there is no consensus. We studied the effects of H. pylori infection on ID/IDA in a cohort of children undergoing upper gastrointestinal endoscopy for upper abdominal pain in two developing and one developed country.Methods
In total 311 children (mean age 10.7±3.2 years) from Latin America - Belo Horizonte/Brazil (n = 125), Santiago/Chile (n = 105) - and London/UK (n = 81), were studied. Gastric and duodenal biopsies were obtained for evaluation of histology and H. pylori status and blood samples for parameters of ID/IDA.Results
The prevalence of H. pylori infection was 27.7% being significantly higher (p<0.001) in Latin America (35%) than in UK (7%). Multiple linear regression models revealed H. pylori infection as a significant predictor of low ferritin and haemoglobin concentrations in children from Latin-America. A negative correlation was observed between MCV (r = −0.26; p = 0.01) and MCH (r = −0.27; p = 0.01) values and the degree of antral chronic inflammation, and between MCH and the degree of corpus chronic (r = −0.29, p = 0.008) and active (r = −0.27, p = 0.002) inflammation.Conclusions
This study demonstrates that H. pylori infection in children influences the serum ferritin and haemoglobin concentrations, markers of early depletion of iron stores and anaemia respectively. 相似文献18.
Mariana Maschietto Richard D. Williams Tasnim Chagtai Sergey D. Popov Neil J. Sebire Gordan Vujanic Elizabeth Perlman James R. Anderson Paul Grundy Jeffrey S. Dome Kathy Pritchard-Jones 《PloS one》2014,9(10)
Purpose
The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information.Patients and Methods
We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling.Results
From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26–16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36–31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes.Conclusion
This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker. 相似文献19.
Seung-Hyun Kim Bo-Young Cho Hyunna Choi Eun-Soon Shin Young-Min Ye Jong-Eun Lee Hae-Sim Park 《PloS one》2014,9(12)
Background
Two common clinical syndromes of acetylsalicylic acid (aspirin) hypersensitivity, aspirin-exacerbated respiratory disease (AERD) and aspirin-exacerbated cutaneous disease (AECD), were subjected to a genome-wide association study to identify strong genetic markers for aspirin hypersensitivity in a Korean population.Methods
A comparison of SNP genotype frequencies on an Affymetrix Genome-Wide Human SNP array of 179 AERD patients and 1989 healthy normal control subjects (NC) revealed SNPs on chromosome 6 that were associated with AERD, but not AECD. To validate the association, we enrolled a second cohort comprising AERD (n = 264), NC (n = 238) and disease-control (aspirin tolerant asthma; ATA, n = 387) groups.Results
The minor genotype frequency (AG or AA) of a particular SNP, rs3128965, in the HLA-DPB1 region was higher in the AERD group compared to the ATA or NC group (P = 0.001, P = 0.002, in a co-dominant analysis model, respectively). Comparison of rs3128965 alleles with the clinical features of asthmatics revealed that patients harboring the A allele had increased bronchial hyperresponsiveness to inhaled aspirin and methacholine, and higher 15-HETE levels, than those without the A allele (P = 0.039, 0.037, and 0.004, respectively).Conclusions
This implies the potential of rs3128965 as a genetic marker for diagnosis and prediction of the AERD phenotype. 相似文献20.
Gustavo Palacios Mady Hornig Daniel Cisterna Nazir Savji Ana Valeria Bussetti Vishal Kapoor Jeffrey Hui Rafal Tokarz Thomas Briese Elsa Baumeister W. Ian Lipkin 《PloS one》2009,4(12)