197 research outputs found
Promoter Elements and Factors Involved In Hepatic Transcription of the Human Apoa-i Gene Positive and Negative Regulators Bind To Overlapping Sites
No full textDNase I footprinting analysis of the proximal apoA-I promoter sequences with rat liver nuclear extracts identified four protected regions: A, -22 to +17; B, -128 to -77; C, -175 to -148; and D, -220 to -190. Region D (-220 to -190) binds at least two distinct activities, designated AID1 and AID2, respectively, which can be separated by ion exchange chromatography. Region C (-175 to -148) forms five DNA protein complexes. Three of the complexes (2, 4, and 5) originate from the binding of more than one heat-stable nuclear factor, and two (1 and 3), from the binding of two heat-labile factors. The heat-stable factors bind in the -175 to -148 region and can be distinguished from C/EBP, which recognizes the same region, with DNA binding gel electrophoretic assays. Both factors 1 and 3 bind in the -168 to -148 apoA-I region. Despite the lack of a CCAAT motif in this region, the binding of factor 1 is competed out by oligonucleotides containing the binding sites of NFY and NFY*. Mutagenesis of the promoter region showed that mutations in the -171 to -166 and -158 to -153 regions diminished the binding of the heat-stable factors and reduced hepatic transcription to 14 and 8% of control, respectively. In contrast, a mutation in the -164 to -159 region abolished the binding of factor 1 and was associated with a 4.6-fold increase in hepatic transcription. These findings suggest that the heat-stable factors act as positive regulators, whereas factor 1 acts as a negative regulator in apoA-I gene transcription
Treatment-emergent antidrug antibodies related to PD-1, PD-L1, or CTLA-4 inhibitors across tumor types: A systematic review
No full textBackground Increased understanding of how the immune system regulates tumor growth has innovated the use of immunotherapeutics to treat various cancers. The impact of such therapies, including programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, on the production of antidrug antibodies (ADAs) and their impact on outcomes, is poorly understood. This study aims to evaluate the clinical trial evidence on ADA incidence associated with PD-1, PD-L1, and CTLA-4 inhibitors in the treatment of cancer and to assess associations between treatment administered, ADA incidence, and treatment outcomes. Methods Embase ®, Medline ®, and EBM Reviews were searched via the OVID ® platform on February 15, 2022. Conference proceedings, clinical trial registries, and global regulatory and reimbursement body websites were also searched. Eligible publications included clinical trials enrolling patients receiving cancer treatment with either PD-1, PD-L1, or CTLA-4 reporting outcomes including incidence or prevalence of ADAs and the impact of immunogenicity on treatment safety and efficacy. Reference lists of eligible publications were also searched. The review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and evidence quality assessment was conducted using the appropriate Joanna Briggs Institute Critical Appraisal tool. Results After screening 4160 records and reviewing 97 full publications, a total of 34 publications reporting on 68 trials were included. A further 41 relevant clinical trials were identified on ClinicalTrials.gov and a further 32 from searches of packaging inserts. In total, 141 relevant trials covering 15 different checkpoint inhibitors and 16 different tumor types were included. Across the included trials, atezolizumab was associated with the highest incidence of ADAs (29.6% of 639 patients), followed by nivolumab (11.2% of 2,085 patients). Combination checkpoint inhibitor treatment appeared to increase the rate of ADAs versus monotherapy. Only 17 trials reported on the impact of ADAs on treatment outcomes with mixed results for the impact of ADAs on treatment efficacy, safety, and pharmacokinetics. Conclusions Checkpoint inhibitors for the treatment of cancer are immunogenic, with the incidence of treatment-emergent ADAs varying between individual therapies. It remains unclear what impact ADAs have on treatment outcomes
अांबेडकर
No full textA corpus of grindmill songs dedicated to the memory of Bhimrao Ramji Ambedkar (1891-1956) by Mahar women in Maharashtra (India)Un corpus de canciones de la molienda dedicados a la memoria de Bhimrao Ramji Ambedkar (1891-1956) por las mujeres Mahar en Maharashtra (India)Corpus de chants de la mouture par des femmes de caste Mahar au Maharashtra (Inde) à la mémoire de Bhimrao Ramji Ambedkar (1891-1956)महाराष्ट्रातील महार स्त्रियांनी भीमराव रामजी आंबेडकरांच्या स्मृतीस वाहीलेली गाणी (१८९१-१९५६)BEL, B. Le corpus « Ambedkar ». Travaux Interdisciplinaires du Laboratoire Parole et Langage d'Aix-en-Provence (TIPA), no. 25. 2006, p. 19-30.http://hal.archives-ouvertes.fr/hal-0013639
Predictors of carotid intima-media thickness and carotid plaque in young Indian adults: the New Delhi Birth Cohort
No full textExploring Intersections of Employment and Ethnicity Amongst British Pakistani Young Men.
No full textThis article draws upon research conducted amongst young British Pakistani men in Lancashire to explore how different boundaries of British Pakistani identity are being constructed. It focuses on the significance of employment within Pakistani men\'s inter and intra-ethnic peer group relations and the ways in which the social dynamics that underlie those relations provide the context for understanding the particular nature and form that ethnicity takes. It does this through the narratives of professional and non-professional men. The article has two aims, firstly it seeks to contribute to the literature on understanding ethnic identity by looking at boundaries as they manifest themselves and suggesting one way in which ethnicity can be understood within a specific social context. Secondly, in so doing it hopes to extend research focus on British Pakistanis away from conventional agendas.Employment, Ethnicity, Class, British Pakistani Men
Genetic variants in lipid metabolism are independently associated with multiple features of the metabolic syndrome
No full textAbstract Background Our objective was to find single nucleotide polymorphisms (SNPs), within transcriptional pathways of glucose and lipid metabolism, which are related to multiple features of the metabolic syndrome (MetS). Methods 373 SNPs were measured in 3575 subjects of the Doetinchem cohort. Prevalence of MetS features, i.e. hyperglycemia, abdominal obesity, decreased HDL-cholesterol levels and hypertension, were measured twice in 6 years. Associations between the SNPs and the individual MetS features were analyzed by log-linear models. For SNPs related to multiple MetS features (P Results Two SNPs, CETP Ile405Val and APOE Cys112Arg, were associated with both the prevalence of low HDL-cholesterol level (Ile405Val P = Cys112Arg P = 0.001) and with the prevalence of abdominal obesity (Ile405Val P = 0.007; Cys112Arg P = 0.007). For both SNPs, the association with HDL-cholesterol was partly independent of the association with abdominal obesity and vice versa. Conclusion Two SNPs, mainly known for their role in lipid metabolism, were associated with two MetS features i.e., low HDL-cholesterol concentration, as well as, independent of this association, abdominal obesity. These SNPs may help to explain why low HDL-cholesterol levels and abdominal obesity frequently co-occur.</p
Childhood body mass index and adult pro-inflammatory and pro-thrombotic risk factors: data from the New Dehli birth cohort
No full textObjective: Weight gain and growth in early life may influence adult pro-inflammatory and pro-thrombotic cardiovascular risk factors. Methods: Follow-up of a birth cohort in New Delhi, India, whose weight and height were measured every 6 months until age 21 years. Body mass index (BMI) at birth, during infancy (2 years), childhood (11 years) and adulthood (26–32 years) and BMI gain between these ages were analysed in 886 men and 640 women with respect to adult fibrinogen, high-sensitivity C-reactive protein (hsCRP) and plasminogen activator inhibitor-1 (PAI-1) concentrations. Results: All the pro-inflammatory/pro-thrombotic risk factors were higher in participants with higher adiposity. In women, BMI at birth and age 2 years was inversely related to fibrinogen (P?=?0.002 and 0.05) and, after adjusting for adult adiposity, to hsCRP (P?=?0.02 and 0.009). After adjusting for adult adiposity, BMI at 2 years was inversely related to hsCRP and PAI-1 concentrations (P?<?0.001 and 0.02) in men. BMI gain between 2 and 11 years and/or 11 years to adulthood was positively associated with fibrinogen and hsCRP in women and with hsCRP and PAI-1 in men. Conclusions: Thinness at birth or during infancy, and accelerated BMI gain during childhood/adolescence are associated with a pro-inflammatory/pro-thrombotic state in adult life. An altered inflammatory state could be one link between small newborn/infant size and adult cardiovascular disease. Associations between pro-inflammatory markers and childhood/adolescent BMI gain are probably mediated through adult adiposity. <br/
Molecular basis of resistance in wheat varieties against spot blotch disease
No full textDuring present investigation, among the six wheat genotypes tested against six isolates of Bipolaris sorokiniana, the genotype BOW‘S’ showed resistance response against three isolates, namely, BS-D-1, BS-DWRK-2 and BS-K-4, whereas moderately resistance response against remaining 3 isolates i.e. BS-F-3, BS-P-5 and BS-V-6.The genotype A-9-30-1 showed almost highly susceptible response against each isolate except BS-D-1 which exhibited susceptible reaction on this genotype. Thus, it is clear that genotype BOW ‘S’ has broad genetic base for resistance, whereas genotype A-9-30-1 has no gene for resistance against these six isolates tested. Remaining five genotypes showed varying response, ranging from highly susceptible, susceptible, moderately susceptible, moderately resistant and resistant against various isolates of B. sorokiniana tested
Adult metabolic syndrome abd impaired glucose tolerance are associated with different patterns of BMI from the New Delhi birth cohort
No full textObjective: the purpose of this study was to describe patterns of infant, childhood, and adolescent BMI and weight associated with adult metabolic risk factors for cardiovascular disease. Research design and methods: we measured waist circumference, blood pressure, glucose, insulin and lipid concentrations, and the prevalence of metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel III definition) in 1,492 men and women aged 26–32 years in Delhi, India, whose weight and height were recorded every 6 months throughout infancy (0–2 years), childhood (2–11 years), and adolescence (11 years–adult). Results: men and women with metabolic syndrome (29% overall), any of its component features, or higher (greater than upper quartile) insulin resistance (homeostasis model assessment) had more rapid BMI or weight gain than the rest of the cohort throughout infancy, childhood, and adolescence. Glucose intolerance (impaired glucose tolerance or diabetes) was, like metabolic syndrome, associated with rapid BMI gain in childhood and adolescence but with lower BMI in infancy. Conclusion: in this Indian population, patterns of infant BMI and weight gain differed for individuals who developed metabolic syndrome (rapid gain) compared with those who developed glucose intolerance (low infant BMI). Rapid BMI gain during childhood and adolescence was a risk factor for both disorders
Association between anthropometry, cardiometabolic risk factors, and early life factors & adult measures of endothelial function: Results from the New Delhi Birth Cohort
No full textBACKGROUND & OBJECTIVES: Abnormal endothelial function represents a preclinical marker of atherosclerosis. This study was conducted to evaluate associations between anthropometry, cardiometabolic risk factors, and early life factors and adult measures of endothelial function in a young urban Indian cohort free of clinical cardiovascular disease.METHODS: Absolute changes in brachial artery diameter following cuff inflation and sublingual nitroglycerin (400 µg) were recorded to evaluate endothelium-dependent and -independent measures of endothelial function in 600 participants (362 men; 238 women) from the New Delhi Birth Cohort (2006-2009). Data on anthropometry, cardiometabolic risk factors, medical history, socio-economic position, and lifestyle habits were collected. Height and weight were recorded at birth, two and 11 yr of age. Age- and sex-adjusted linear regression models were developed to evaluate these associations.RESULTS: The mean age of participants was 36±1 yr. Twenty two per cent men and 29 per cent women were obese (BMI th > 30 kg/m [2] ). Mean systolic blood pressure (SBP) was 131±14 and 119±13 mmHg, and diabetes prevalence was 12 and 8 per cent for men and women, respectively. Brachial artery diameter was higher for men compared with women both before (3.48±0.37 and 2.95±0.35 cm) and after hyperaemia (3.87±0.37 vs. 3.37±0.35 cm). A similar difference was seen before and after nitroglycerin. Markers of increased adiposity, smoking, SBP, and metabolic syndrome, but not early life anthropometry, were inversely associated with endothelial function after adjustment for age and sex.INTERPRETATION & CONCLUSIONS: The analysis of the current prospective data from a young urban Indian cohort showed that cardiometabolic risk factors, but not early life anthropometry, were associated with worse endothelial function
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