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1.
Efe Sezgin Joanne M. Lind Sadeep Shrestha Sher Hendrickson James J. Goedert Sharyne Donfield Gregory D. Kirk John P. Phair Jennifer L. Troyer Stephen J. O’Brien Michael W. Smith 《Human genetics》2009,125(3):281-294
The host genetic basis of differential outcomes in HIV infection, progression, viral load set point and highly active retroviral
therapy (HAART) responses was examined for the common Y haplogroups in European Americans and African Americans. Accelerated
progression to acquired immune deficiency syndrome (AIDS) and related death in European Americans among Y chromosome haplogroup
I (Y-I) subjects was discovered. Additionally, Y-I haplogroup subjects on HAART took a longer time to HIV-1 viral suppression
and were more likely to fail HAART. Both the accelerated progression and longer time to viral suppression results observed
in haplogroup Y-I were significant after false-discovery-rate corrections. A higher frequency of AIDS-defining illnesses was
also observed in haplogroup Y-I. These effects were independent of the previously identified autosomal AIDS restriction genes.
When the Y-I haplogroup subjects were further subdivided into six I subhaplogroups, no one subhaplogroup accounted for the
effects on HIV progression, viral load or HAART response. Adjustment of the analyses for population stratification found significant
and concordant haplogroup Y-I results. The Y chromosome haplogroup analyses of HIV infection and progression in African Americans
were not significant. Our results suggest that one or more loci on the Y chromosome found on haplogroup Y-I have an effect
on AIDS progression and treatment responses in European Americans.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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3.
Mario León Silva-Vergara Ivonete Helena Rocha Rakel Rocha Vasconcelos André Luiz Maltos Fernando de Freitas Neves Luciana de Almeida Silva Teixeira Delio José Mora 《Mycopathologia》2014,177(1-2):137-141
Up to now, over 200 patients with paracoccidioidomycosis (PCM) associated to HIV infection have already been reported; however, the central nervous system involvement in this coinfection was rarely reported. This paper presents a 35-year-old Brazilian male AIDS patient who developed pulmonary PCM successfully treated with itraconazole. At the antiretroviral therapy starting, he had 32 CD4+ T cells baseline count and high viral load levels. After 9 months, he presented severe fungal meningoencephalitis diagnosed by sublenticular enhanced nodular lesion at computerized tomography and magnetic resonance brain imaging and a positive Paracoccidiodes brasiliensis smear and culture from cerebrospinal fluid. At the time, a sixfold increase in CD4+ T cell count and undetectable viral load level were evidenced. The patient received amphotericin B during 1 year presenting slow but progressive clinical improvement, and he is currently asymptomatic and without neurological disabilities. To our knowledge, this is the second case report of a patient with neuroparacoccidioidomycosis associated to HIV infection. 相似文献
4.
Jessica N. Cooke Bailey Nicholette D. Palmer Maggie C. Y. Ng Jason A. Bonomo Pamela J. Hicks Jessica M. Hester Carl D. Langefeld Barry I. Freedman Donald W. Bowden 《Human genetics》2014,133(6):769-779
Prior studies have identified common genetic variants influencing diabetic and non-diabetic nephropathy, diseases which disproportionately affect African Americans. Recently, exome sequencing techniques have facilitated identification of coding variants on a genome-wide basis in large samples. Exonic variants in known or suspected end-stage kidney disease (ESKD) or nephropathy genes can be tested for their ability to identify association either singly or in combination with known associated common variants. Coding variants in genes with prior evidence for association with ESKD or nephropathy were identified in the NHLBI-ESP GO database and genotyped in 5,045 African Americans (3,324 cases with type 2 diabetes associated nephropathy [T2D-ESKD] or non-T2D ESKD, and 1,721 controls) and 1,465 European Americans (568 T2D-ESKD cases and 897 controls). Logistic regression analyses were performed to assess association, with admixture and APOL1 risk status incorporated as covariates. Ten of 31 SNPs were associated in African Americans; four replicated in European Americans. In African Americans, SNPs in OR2L8, OR2AK2, C6orf167 (MMS22L), LIMK2, APOL3, APOL2, and APOL1 were nominally associated (P = 1.8 × 10?4–0.044). Haplotype analysis of common and coding variants increased evidence of association at the OR2L13 and APOL1 loci (P = 6.2 × 10?5 and 4.6 × 10?5, respectively). SNPs replicating in European Americans were in OR2AK2, LIMK2, and APOL2 (P = 0.0010-0.037). Meta-analyses highlighted four SNPs associated in T2D-ESKD and all-cause ESKD. Results from this study suggest a role for coding variants in the development of diabetic, non-diabetic, and/or all-cause ESKD in African Americans and/or European Americans. 相似文献
5.
Glucia Elisete Barbosa Marcon Juliana de Jesus Guimares Ferreira Eros Antonio de Almeida Adriane Maira Delicio Mariane Barroso Pereira Jamiro da Silva Wanderley Luiz Cludio Martins Paula Durante Andrade Rodrigo Gonalves de Lima Sandra Cecília Botelho Costa 《PLoS neglected tropical diseases》2022,16(3)
Chagas disease also known as American trypanosomiasis, is caused by Trypanosoma cruzi and transmitted by triatominae-contaminated feces. It is considered a neglected tropical disease that affects 6 to 7 million people worldwide. The reactivation of Chagas disease occurs when the chronically infected hosts are not able to control T. cruzi infection, generating recurrence of the acute phase. HIV is the main immunosuppressive infection that can lead to the reactivation of chronic Chagas disease in AIDS conditions. In co-infected patients, the reactivation of Chagas disease is related to their high parasite load, high HIV viral load, and CD4 T-cell counting less than 200/mm3, which may evolve to meningoencephalitis and myocarditis. Eight T. cruzi/HIV co-infected patients under antiretroviral therapy (ART) and ten Chagas disease patients without HIV infection that attended at Study Group of Chagas Disease, Hospital de Clínicas, University of Campinas (GEdoCh/HC/UNICAMP-SP) and Pontifical Catholic University of Campinas SP (PUCC/SP) were evaluated. Tests for Chagas disease were performed, such as qPCR and T. cruzi blood culture. The patient’s medical records were analyzed to verify clinical and epidemiological data, viral load, and CD4 T-cell counting since the outset of ART. For both groups, we found no statically significant differences between parasite load via blood culture and qPCR. In T. cruzi/HIV co-infected subjects, we observed a significant increase of CD4 T-cells counting and viral load decrease, which became undetectable over the years after ART. Parasites isolated from the patient’s blood culture were genotyped, being the majority of them infected with TcII and one case of mixed infection (TcII and TcV/TcVI). These results were expected according to the region of origin of the patients. We suggest that the parasite load be monitored through qPCR in T.cruzi/HIV co-infected patients. We conclude that ART in people living with HIV improves infection and immunosuppression control, enabling the natural evolution of the American trypanosomiasis. 相似文献
6.
Jacob M. Keaton Jessica N. Cooke Bailey Nicholette D. Palmer Barry I. Freedman Carl D. Langefeld Maggie C. Y. Ng Donald W. Bowden 《Human genetics》2014,133(12):1487-1495
The prevalence of type 2 diabetes (T2D) is greater in populations of African descent compared to European-descent populations. Genetic risk factors may underlie the disparity in disease prevalence. Genome-wide association studies (GWAS) have identified >60 common genetic variants that contribute to T2D risk in populations of European, Asian, African and Hispanic descent. These studies have not comprehensively examined population differences in cumulative risk allele load. To investigate the relationship between risk allele load and T2D risk, 46 T2D single nucleotide polymorphisms (SNPs) in 43 loci from GWAS in European, Asian, and African-derived populations were genotyped in 1,990 African Americans (n = 963 T2D cases, n = 1,027 controls) and 1,644 European Americans (n = 719 T2D cases, n = 925 controls) ascertained and recruited using a common protocol in the southeast United States. A genetic risk score (GRS) was constructed from the cumulative risk alleles for each individual. In African American subjects, risk allele frequencies ranged from 0.024 to 0.964. Risk alleles from 26 SNPs demonstrated directional consistency with previous studies, and 3 SNPs from ADAMTS9, TCF7L2, and ZFAND6 showed nominal evidence of association (p < 0.05). African American individuals carried 38–67 (53.7 ± 4.0, mean ± SD) risk alleles. In European American subjects, risk allele frequencies ranged from 0.084 to 0.996. Risk alleles from 36 SNPs demonstrated directional consistency, and 10 SNPs from BCL11A, PSMD6, ADAMTS9, ZFAND3, ANK1, CDKN2A/B, TCF7L2, PRC1, FTO, and BCAR1 showed evidence of association (p < 0.05). European American individuals carried 38–65 (50.9 ± 4.4) risk alleles. African Americans have a significantly greater burden of 2.8 risk alleles (p = 3.97 × 10?89) compared to European Americans. However, GRS modeling showed that cumulative risk allele load was associated with risk of T2D in European Americans, but only marginally in African Americans. This result suggests that there are ethnic-specific differences in genetic architecture underlying T2D, and that these differences complicate our understanding of how risk allele load impacts disease susceptibility. 相似文献
7.
Lai He Jin Zhao Maggie Haitian Wang Kenny K. Y. Siu Yong-Xia Gan Lin Chen Benny C. Y. Zee Li Yang Hsiang-Fu Kung Zheng-Rong Yang Ming-Liang He 《PloS one》2014,9(5)
Human Immunodeficiency Virus (HIV) infection and the resultant Acquired Immunodeficiency Syndrome (AIDS) epidemic are major global health challenges; hepatitis C virus (HCV) co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27), a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection. 相似文献
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9.
Ping An Sudhir Penugonda Christian W. Thorball Istvan Bartha James J. Goedert Sharyne Donfield Susan Buchbinder Elizabeth Binns-Roemer Gregory D. Kirk Wenyan Zhang Jacques Fellay Xiao-Fang Yu Cheryl A. Winkler 《PLoS genetics》2016,12(3)
Human APOBEC3 cytidine deaminases are intrinsic resistance factors to HIV-1. However, HIV-1 encodes a viral infectivity factor (Vif) that degrades APOBEC3 proteins. In vitro APOBEC3F (A3F) anti-HIV-1 activity is weaker than A3G but is partially resistant to Vif degradation unlike A3G. It is unknown whether A3F protein affects HIV-1 disease in vivo. To assess the effect of A3F gene on host susceptibility to HIV- acquisition and disease progression, we performed a genetic association study in six well-characterized HIV-1 natural cohorts. A common six-Single Nucleotide Polymorphism (SNP) haplotype of A3F tagged by a codon-changing variant (p. I231V, with allele (V) frequency of 48% in European Americans) was associated with significantly lower set-point viral load and slower rate of progression to AIDS (Relative Hazards (RH) = 0.71, 95% CI: 0.56, 0.91) and delayed development of pneumocystis pneumonia (PCP) (RH = 0.53, 95% CI: 0.37–0.76). A validation study in the International Collaboration for the Genomics of HIV (ICGH) showed a consistent association with lower set-point viral load. An in vitro assay revealed that the A3F I231V variant may influence Vif mediated A3F degradation. Our results provide genetic epidemiological evidence that A3F modulates HIV-1/AIDS disease progression. 相似文献
10.
A dynamic analysis of viral load, T lymphocyte subsets and main biochemical indexes before and after prevention of mother to child transmission (PMTCT) in HIV/AIDS
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Guosheng Su Yesheng Wei Lihua Qin Lida Mo 《Asia-Pacific Journal of Blood Types and Genes》2018,2(4):223-231
This study aims to investigate changes in viral load, T lymphocyte subsets and other main biochemical indexes of HIV/AIDS in the prevention of mother to child transmission (PMTCT). In this study, 152 pregnant women with HIV/AIDS enrolled into our hospital from January 2013 to June 2015 were chosen as objects. Changes in viral load, T lymphocyte subsets and other main biochemical indexes of HIV/AIDS were tested and compared before and after 3 months of PMTCT and in neonatals one week after birth. The CD4/CD8 examination result, and difference in CD4 before and after prevention (in the newborns after a week) was statistically significant (P < 0.05), and the rest showed no statistical significance. For the dynamic analysis of main biochemical test results: K+, Na+, Cl-, BG, OS, BUN, BUN/Cr, UA,TDIL, DBIL, TP, ALB, CK, LDH, HDL, LDL and other indexes before and after prevention attained statistical significances (P < 0.05 or above). The same sample in the three groups was detected by repeated analysis of variance, K+, Na+, Cl-, BG, OS, BUN/Cr, UA, DBI L, ALB, CK, LDH, HDL, LDL and other indexes also showing P at less than 0.05 or above, among which K+, Cl-, CK, LDL showed homogeneity of variance, while Na+, BG, OS, BUN/Cr, UA, DBIL, ALB, LDH, HDL showed unequal homogeneity of variance. The study suggests that the dynamic analysis of viral load, T lymphocyte subsets and main biochemical indexes before and after PMTCT in HIV/AIDS are important means to evaluate the dose and treatment of antiretroviral drugs. Monitoring of above indexes is helpful to judge and analyze the condition of the maternal body at various stages, so antiviral drug treatment can be adjusted. 相似文献
11.
Joshua T. Herbeck John E. Mittler Geoffrey S. Gottlieb James I. Mullins 《PLoS computational biology》2014,10(6)
Trends in HIV virulence have been monitored since the start of the AIDS pandemic, as studying HIV virulence informs our understanding of HIV epidemiology and pathogenesis. Here, we model changes in HIV virulence as a strictly evolutionary process, using set point viral load (SPVL) as a proxy, to make inferences about empirical SPVL trends from longitudinal HIV cohorts. We develop an agent-based epidemic model based on HIV viral load dynamics. The model contains functions for viral load and transmission, SPVL and disease progression, viral load trajectories in multiple stages of infection, and the heritability of SPVL across transmissions. We find that HIV virulence evolves to an intermediate level that balances infectiousness with longer infected lifespans, resulting in an optimal SPVL∼4.75 log10 viral RNA copies/mL. Adaptive viral evolution may explain observed HIV virulence trends: our model produces SPVL trends with magnitudes that are broadly similar to empirical trends. With regard to variation among studies in empirical SPVL trends, results from our model suggest that variation may be explained by the specific epidemic context, e.g. the mean SPVL of the founding lineage or the age of the epidemic; or improvements in HIV screening and diagnosis that results in sampling biases. We also use our model to examine trends in community viral load, a population-level measure of HIV viral load that is thought to reflect a population''s overall transmission potential. We find that community viral load evolves in association with SPVL, in the absence of prevention programs such as antiretroviral therapy, and that the mean community viral load is not necessarily a strong predictor of HIV incidence. 相似文献
12.
Geldmacher C Gray C Nason M Currier JR Haule A Njovu L Geis S Hoffmann O Maboko L Meyerhans A Cox J Hoelscher M 《Journal of virology》2007,81(24):13809-13815
Human immunodeficiency virus (HIV)-specific CD8 T-cell responses targeting products encoded within the Gag open reading frame have frequently been associated with better viral control and disease outcome during the chronic phase of HIV infection. To further clarify this relationship, we have studied the dynamics of Gag-specific CD8 T-cell responses in relation to plasma viral load and time since infection in 33 chronically infected subjects over a 9-month period. High baseline viral loads were associated with a net loss of breadth (P < 0.001) and a decrease in the total magnitude of the Gag-specific T-cell response in general (P = 0.03). Most importantly, the baseline viral load predicted the subsequent change in the breadth of Gag recognition over time (P < 0.0001, r2 = 0.41). Compared to maintained responses, lost responses were low in magnitude (P < 0.0001) and subdominant in the hierarchy of Gag-specific responses. The present study indicates that chronic exposure of the human immune system to high levels of HIV viremia is a determinant of virus-specific CD8 T-cell loss. 相似文献
13.
Viviane Martha Santos de Morais Elker Lene Santos de Lima Georgea Gertrudes de Oliveira Mendes Cahú Thaisa Regina Rocha Lopes Juliana Prado Gonçales Maria Tereza Cartaxo Muniz Maria Rosângela Cunha Duarte Coêlho 《Retrovirology》2018,15(1):75
Background
Host genetic factors such as MBL2 gene polymorphisms cause defects in the polymerization of MBL protein and result in a functional deficiency and/or in low serum levels that can influence susceptibility to various viral infections. The aim of this study was to estimate the frequency of alleles, genotypes and haplotypes related to -550, -221 and exon 1 polymorphisms of the MBL2 gene and investigate their association with HHV-8 in people living with HIV/AIDS (PLWHA), as well as the impacts on CD4 cell count and HIV viral load in HIV/HHV-8 coinfected and HIV monoinfected patients.Results
A cross sectional study in PLWHA, with and without HHV-8 infection, exploring associations between different factors, was performed in the outpatient infectious and parasitic diseases clinic at a referral hospital. Genomic DNA extractions from leukocytes were performed using a commercial Wizard® Genomic DNA Purification kit (Promega, Madison, WI). The promoter region (-550 and -221) was genotyped with the TaqMan system (Applied TaqMan Biosystems® genotyping Assays), and the structural region (exon1) was genotyped with Express Sybr Greener Supermix kit (Invitrogen, USA). In total, 124 HIV/HHV-8 coinfected and 213 HIV monoinfected patients were analysed. Median TCD4 counts were significantly lower in HIV/HHV-8 coinfected patients, whereas the mean of the first and last viral load of HIV did not present significant difference. There was no difference in frequency between the LL, YY and AA genotypes between the HIV/HHV-8 coinfected or HIV monoinfected patients. However, in a multivariate analysis, coinfected patients with the intermediate expression haplotype of the MBL2 gene had an odds ratio of 3.1-fold (CI?=?1.2–7.6) of their last CD4 cell count being below 350 cells/mm3. Among the coinfected individuals, four developed KS and presented the intermediate expression MBL haplotype, with three being HYA/LXA and one being LYA/LYO.Conclusions
Host genetic factors, such as -550, -221 and exon 1 polymorphisms, can be related to the may modify coinfections and/or to the development clinical manifestations caused by HHV-8, especially in HIV/HHV-8 coinfected patients who present the intermediate expression haplotypes of MBL.14.
Candida albicans is the most frequently isolated yeast from the oral cavity of HIV/AIDS individuals. The use of fluconazole has increased the number of resistant or less-sensitive Candida species different than C. albicans. The purpose of this study was to identify the Candida species producing pseudomembranous candidiasis in patients suffering from AIDS, their relationship with CD4+ counts and their sensitivity to fluconazole and itraconazole. We studied 71 patients at a hospital in the city of Cali. Samples of white plaque were seeded on CHROMagar Candida, yeast identification was done with API 20C Aux, and susceptibility testing was determined by E test. Ninety-three yeast isolates were obtained, 52 single and 41 mixed. C. albicans was the most isolated, followed by C. glabrata. An increased frequency of isolates and variety of Candida species occurred in patients with a CD4+ cell count ≤100 cells/mm3 without significant differences (p = 0.29). The susceptibility study showed that 8 (8.6 %) isolates were resistant to fluconazole and 11 (11.8 %) to itraconazole, while 6 (8.8 %) C. albicans were simultaneously resistant. No association was found between the isolates of C. albicans or Candida species different than C. albicans and the use of fluconazole (p = 0.21). The results of this study indicate that in the tested population, fluconazole continues to be the best treatment option for oropharyngeal candidiasis in patients suffering from AIDS (HIV/AIDS); however, susceptibility tests are necessary in patients who present therapeutic failure. 相似文献
15.
Takushi Nomura Hiroyuki Yamamoto Hiroshi Ishii Hirofumi Akari Taeko K. Naruse Akinori Kimura Tetsuro Matano 《PLoS pathogens》2015,11(11)
Control of HIV replication is a rare immunological event, providing clues to understand the viral control mechanism. CD8+ T-cell responses are crucial for virus control, but it is unclear whether lasting HIV containment can be achieved after establishment of infection. Here, we describe lasting SIV containment in a macaque AIDS model. Analysis of ten rhesus macaques that controlled viremia for 2 years post-infection found accumulation of proviral gag and nef CD8+ T-cell escape mutations in four of them. These four controllers mounted CD8+ T cells targeting Gag, Nef, and other viral proteins at 4 months, suggesting that broadening of CD8+ T-cell targets can be an indicator of the beginning of viral control failure. The remaining six aviremic SIV controllers, however, harbored proviruses without mutations and showed no or little broadening of their CD8+ T-cell responses in the chronic phase. Indeed, three of the latter six exhibiting no change in CD8+ T-cell targets showed gradual decreases in SIV-specific CD8+ T-cell frequencies, implying a concomitant reduction in viral replication. Thus, stability of the breadth of virus-specific CD8+ T-cell responses may represent a status of lasting HIV containment by CD8+ T cells. 相似文献
16.
Jingwan Han Siyang Liu Wei Guo Zuoyi Bao Xiaolin Wang Lin Li Yongjian Liu Daomin Zhuang Hanping Li Lei Jia Tao Gui Hongshuai Sui Tianyi Li Jingyun Li 《PloS one》2015,10(5)
BackgroundThe complex epidemic and significant diversity of HIV-1 strains in China pose serious challenges for surveillance and diagnostic assays, vaccine development and clinical management. There is a lack of HIV-1 isolates in current canonical HIV-1 subtype panels that can represent HIV-1 diversity in China; an HIV-1 subtype panel for China is urgently needed.MethodsBlood samples were collected from HIV-1 infected patients participating in the drug-resistance surveillance program in China. The samples were isolated, cultured and stored as neat culture supernatant. The HIV-1 isolates were fully characterized. The panel was used to compare 2 viral load assays and 2 p24 assays as the examples of how this panel could be used.ResultsAn HIV-1 subtype panel for China composed of 30 HIV-1 primary strains of four subtypes (B [including Thai-B], CRF01_AE, CRF07_BC and G) was established. The samples were isolated and cultured to a high-titer (106-109 copies/ml)/high-volume (40ml). The HIV-1 isolates were fully characterized by the final viral load, p24 concentration, gag-pol and envC2V3 sequencing, co-receptor prediction, determination of the four amino acids at the tip of the env V3-loop, glycosylation sites in the V3 loop and the drug-resistance mutations. The comparison of two p24 assays and two viral load assays on the isolates illustrated how this panel may be used for the evaluation of diagnostic assay performance. The Pearson value between p24 assays were 0.938. The viral load results showed excellent concordance and agreement for samples of Thai-B, but lower correlations for samples of CRF01_AE.ConclusionThe current panel of 30 HIV-1 isolates served as a basis for the development of a comprehensive panel of fully characterized viral isolates, which could reflect the current dynamic and complex HIV-1 epidemic in China. This panel will be available to support HIV-1 research, assay evaluation, vaccine and drug development. 相似文献
17.
María L. Parages Rosa M. Rico Roberto T. Abdala-Díaz Mariana Chabrillón Theodore G. Sotiroudis Carlos Jiménez 《Journal of applied phycology》2012,24(6):1537-1546
The study of the enhancement of the immune system by administration of algal cell components is a current research field of great interest for future development of algal biotechnology. Arthrospira (Spirulina) platensis is one of the key organisms, showing interesting results in the treatment of certain tumors, viral infection, and immunodeficiency. Polysaccharides from Arthrospira, together with phycocyanin, seem to be responsible for most of these positive effects. In this work, we isolated the acidic polysaccharide fraction from A. platensis and tested its capacity to induce the production of the proinflammatory cytokine tumor necrosis factor alpha in macrophages. For this purpose, we modified a previous isolation method developed by one of us, which includes several depigmentation steps, as well as differential partitioning with N-cetylpyridinium bromide (Cetavlon). Infrared spectroscopy of the acidic polysaccharide fraction indicates the presence of hydroxyl radicals, aliphatic residues, carbonyl groups, sulfate groups, and sulfate esters, as well as amine residues. Liquid chromatography confirmed the polysaccharidic nature of the fraction, revealing its high purity, essentially free of lipopolysaccharide (LPS) contamination (0.0017% w/w), and complying with international pharmacological standards. The results indicate that a very high production of tumor necrosis factor- α (TNF?α) occurred in macrophages in the presence of the polysaccharides in the range 5–100 μg mL?1, reaching values of 8 ng TNF-α mL?1 after 24 h and 30 ng TNF-α mL?1 after 48 h. These data demonstrate that acidic polysaccharides from Spirulina elicit TNF-α production levels comparable to LPS at ~100× higher concentration than LPS, but without significantly increasing the risk of septic shock or deleterious pyrogenesis. 相似文献
18.
M. Sivakumar R. Ranjith Kumar V. Shashirekha S. Seshadri 《World journal of microbiology & biotechnology》2014,30(10):2775-2781
Growth of Spirulina sp. (MCRC-A0003), a cyanobacterium, was evaluated under different concentrations of carbon-dioxide (CO2) (4–50 %) in a closed glass photobioreactor. Although significant CO2 utilization by the cyanobacterial strain was observed up to 50 % concentration, complete utilization was observed only at 4, 10 and 20 % concentrations on 3rd, 6th and 8th day respectively. However, considerable reduction was witnessed in reactors containing 30–50 % CO2 only between 6th and 9th day. A corresponding increase in the biomass and primary metabolites like chlorophyll-a, carbohydrate and protein were observed. Biomass productivity of Spirulina in reactors sparged with 4, 10 and 20 % CO2 were 13.7, 43 and 44 % more than that in control reactor without CO2. While CO2 increased the levels of primary metabolites in the cyanobacterial cells, it was quite prominent in 10 % CO2 concentration with the chlorophyll-a, carbohydrate and protein contents were 64, 183 and 626 mg g?1 respectively. While 10 and 6.6 % increase were noticed in chlorophyll-a and protein, 17 % increase in carbohydrate levels was observed in Spirulina cells, which could be attributed to the conversion of CO2 to carbohydrate by the cyanobacterium. 相似文献
19.
《PLoS genetics》2014,10(8)
Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15×10−94<P<5×10−8, odds ratio (OR) = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2×10−23 < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies. 相似文献
20.
Landrum ML Hullsiek KH O'Connell RJ Chun HM Ganesan A Okulicz JF Lalani T Weintrob AC Crum-Cianflone NF Agan BK;Infectious Disease Clinical Research Program HIV Working Group 《PloS one》2012,7(3):e33488