68 research outputs found

    Genetic Variants of APOL1 Are Major Determinants of Kidney Failure in People of African Ancestry With HIV

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    INTRODUCTION: Variants of the APOL1 gene are associated with chronic kidney disease (CKD) in people of African ancestry, although evidence for their impact in people with HIV are sparse. METHODS: We conducted a cross-sectional study investigating the association between APOL1 renal risk alleles and kidney disease in people of African ancestry with HIV in the UK. The primary outcome was end-stage kidney disease (ESKD; estimated glomerular filtration rate [eGFR] of 30 mg/mmol), and biopsy-proven HIV-associated nephropathy (HIVAN). Multivariable logistic regression was used to estimate the associations between APOL1 high-risk genotypes (G1/G1, G1/G2, G2/G2) and kidney disease outcomes. RESULTS: A total of 2864 participants (mean age 48.1 [SD 10.3], 57.3% female) were genotyped, of whom, 354 (12.4%) had APOL1 high-risk genotypes, and 99 (3.5%) had ESKD. After adjusting for demographic, HIV, and renal risk factors, individuals with APOL1 high-risk genotypes were at increased odds of ESKD (odds ratio [OR] 10.58, 95% CI 6.22–17.99), renal impairment (OR 5.50, 95% CI 3.81–7.95), albuminuria (OR 3.34, 95% CI 2.00–5.56), and HIVAN (OR 30.16, 95% CI 12.48–72.88). An estimated 49% of ESKD was attributable to APOL1 high-risk genotypes. CONCLUSION: APOL1 high-risk genotypes were strongly associated with kidney disease in people of African ancestry with HIV and accounted for approximately half of ESKD cases in this cohort

    Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV

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    Introduction: Sickle cell trait (SCT) has been associated with chronic kidney disease (CKD) in African Americans, although evidence for its impact in Africans and people with HIV is currently lacking. We conducted a cross-sectional study investigating the association between SCT and kidney disease in people of African ancestry with HIV in the UK. Methods: The primary outcome was estimated glomerular filtration rate (eGFR) 50 mg/mmol), and albuminuria (albumin-to-creatinine ratio >3 mg/mmol). Multivariable logistic regression was used to estimate the associations between SCT and kidney disease outcomes. Results: A total of 2895 participants (mean age 48.1 [SD 10.3], 57.2% female) were included, of whom 335 (11.6%) had SCT and 352 (12.2%) had eGFR <60 ml/min per 1.73 m2. After adjusting for demographic, HIV, and kidney risk factors including APOL1 high-risk genotype status, individuals with SCT were more likely to have eGFR <60 ml/min per 1.73 m2 (odds ratio 1.62 [95% CI 1.14–2.32]), eGFR <90 ml/min per 1.73 m2 (1.50 [1.14–1.97]), and albuminuria (1.50 [1.09–2.05]). Stratified by APOL1 status, significant associations between SCT and GFR <60 ml/min per 1.73 m2, eGFR <90 ml/min per 1.73 m2, proteinuria, and albuminuria were observed for those with APOL1 low-risk genotypes. Conclusion: Our results extend previously reported associations between SCT and kidney disease to people with HIV. In people of African ancestry with HIV, these associations were largely restricted to those with APOL1 low-risk genotypes

    Uterine Leiomyoma

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    Renal Leiomyoma

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    Influence of storage Time and Temperature on Absorption of Flavour Compounds from Solutions by Plastic Packaging Materials

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    Food packaging, although an integral part of the food chain, has a major drawback in that, often, the packaging material interacts with the flavor constituents of the food, causing either a selective or an extensive loss of desirable food flavors or absorption of undesirable off-flavors from the packaging material, thereby resulting in an eventual loss of quality of the packaged food item. The process is called "scalping" and is of great concern to the food industry, which is always looking out for new avenues in "packaging solutions" for its final product quality needs. The review highlights the various attributes of the scalping process, explores approaches to the reduction of the manifested undesirable effects, and covers other relevant aspects

    Platelet integrin α 2 I-domain specific antibodies produced via domain specific DNA vaccination combined with variable gene phage display

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    Antibodies are a powerful tool for structure/function studies of platelet proteins. However, classic immunisation frequently elicits antibody responses against domains of minor functional interest. Robust strategies to generate antibodies against defined domains would be of significant interest in post-genome research. In this study, we report a new strategy using a combination of DNA vaccination and V gene phage display that allows the rapid generation of domain specific single-chain Fv antibodies (scFvs).This system was validated using the I-domain of a 2 integrin as a model.The a 2 β 1 integrin, which is expressed on many cell types, is the dominant collagen attachment receptor on platelets, functioning in close interplay with the collagen signalling receptor glycoprotein VI. A novel set of I-domain specific antibodies was obtained by a DNA vaccination/V gene repertoire cloning approach. Mice were first immunised with a DNA vaccine in which the α 2 I-domain is expressed as a fusion protein with fragment C of tetanus toxoid (FrC-TT).Then the heavy and kappa light chain variable gene repertoires were rescued from immune splenocytes using antibody phage display. A total of four a 2 I-domain specific scFvs were isolated by selection on recombinant I-domain or native platelet α 2 β 1 integrin. Characterisation of the scFvs indicated that they recognised distinct epitopes that had profound differences in accessibility between native and recombinant I-domain. Our data suggest DNA immunisation and phage display represent versatile alternatives to protein immunisation and hybridoma-fusion techniques for the isolation of recombinant antibody reagents. This approach will be particularly useful for the generation of domain or splicevariant specific antibodies that recognise native protein
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