Acetyl-Heme-Binding Protein 1 (1-21) (human)

Vitamin A circulates in human plasma as retinol bound to a specific transport protein. This protein differs from the known low and high density plasma lipoproteins and has a hydrated density greater than 1.21. In order to study this protein, volunteers were injected intravenously with retinol-15-(14)C. Plasma was collected 1-3 days later, and the purification of retinol-binding protein (RBP) was monitored by assaying for (14)C and also by following the fluorescence of the protein-bound retinol. Purification of RBP was effected by the sequence: Cohn fractionation, chromatography on columns of Sephadex G-200 and diethylaminoethyl (DEAE)-Sephadex, preparative polyacrylamide gel electrophoresis, and finally chromatography on Sephadex G-100. These procedures resulted in a preparation of RBP which was at least 98% pure and which had been purified more than 1500-fold. Purified RBP has alpha(1) mobility on electrophoresis and has a molecular weight of approximately 21,000-22,000. There appears to be one binding site for retinol per molecule of RBP. Solutions of RBP are fluorescent (characteristic of retinol) and have ultraviolet absorption spectra with peaks at 330 mmu (resulting from the bound retinol) and at 280 mmu. There are no fatty acid or fatty acyl chains present in purified RBP. The usual concentration of RBP in plasma is of the order of 3-4 mg/100 ml. In plasma, RBP apparently circulates as a complex, together with another, larger protein with prealbumin mobility on electrophoresis. The RBP-prealbumin complex remains intact during Cohn fractionation and during chromatography on Sephadex and on DEAE-Sephadex columns. The complex dissociates during gel electrophoresis, permitting the isolation and subsequent purification of each of the components. The complex is again formed by mixing together solutions of the separated RBP and of prealbumin. Retinol transport in plasma thus appears to involve both a lipid-protein (retinol-RBP) interaction and a protein-protein (RBP-prealbumin) interaction.

Objective:To conduct a meta-analysis that investigates sex differences in the prevalence of mutations in the 3 most common genes that cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)-chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), or microtubule-associated protein tau (MAPT)-in patients clinically diagnosed with these conditions.Methods:MEDLINE, EMBASE, and PsycINFO databases were searched (inception to June 30, 2016). Studies of patients with FTD or ALS that reported the number of men and women with and without mutations of interest were selected. Female to male pooled risk ratios (RR) and 95% confidence intervals (CI) for each mutation were calculated using random-effects models.Results:Thirty-two articles reporting 12,784 patients with ALS (including 1,244C9orf72mutation carriers) revealed a higher prevalence of female patients withC9orf72-related ALS (RR 1.16, 95% CI 1.04-1.29). Twenty-three articles reporting 5,320 patients with FTD (including 488C9orf72mutation carriers) revealed no sex differences inC9orf72-related FTD (RR 0.95, 95% CI 0.81-1.12). Thirty-six articles reporting 3,857 patients with FTD (including 369GRNmutation carriers) revealed a higher prevalence of female patients withGRN-related FTD (RR 1.33, 95% CI 1.09-1.62). Finally, 21 articles reporting 2,377 patients with FTD (including 215MAPTmutation carriers) revealed no sex difference inMAPT-related FTD (RR 1.21, 95% CI 0.95-1.55).Conclusions:Higher female prevalence ofC9orf72hexanucleotide repeat expansions in ALS andGRNmutations in FTD suggest that sex-related risk factors might moderateC9orf72andGRN-mediated phenotypic expression.

Introduction:Pregnancy and childbirth are considered risk factors for pelvic organ prolapse (POP). The long latency between obstetric events and morbidity hinders the establishment of cause-effect relationships. Recently, intermediate outcomes such as organ descent and levator avulsion (LA) have been identified. We aimed to assess the effect of obstetric events on symptoms and signs of POP and on LA.Methods:We systematically reviewed the literature by searching PubMed/MEDLINE, Embase and Cochrane Library. We included studies in women examining associations between obstetric events and symptoms and signs of POP and LA, assessed through questionnaires, clinical examination and pelvic floor imaging. Two reviewers evaluated the studies for eligibility and for methodological quality/susceptibility to bias. We extracted study results and clustered them by outcome: symptoms of POP (sPOP), clinical findings of POP (cPOP) and LA. When appropriate, we performed a random-effect meta-analysis and reported the summary odds ratios (OR) with 95% confidence intervals. Heterogeneity across studies was assessed using the I2statistic.Results:The first vaginal delivery was a risk factor for POP as measured by sPOP (OR: 2.65 [1.81-3.88]), cPOP (OR: 4.85 [2.15-10.94]) and in association with LA (OR: 41.6 [4.13- 419.41]). Forceps delivery was a risk factor for POP as measured by sPOP (OR: 2.51 [1.34-4.69]), cPOP (OR: 1.68 [1.21-2.34]) and in association with LA (OR: 5.92 [3.75-9.34]). Birth exclusively by caesarean was protective for sPOP (OR: 0.38 [0.29-0.51]) and for cPOP (OR: 0.29 [0.20-0.41]) and it did not confer any additional risk compared to nulliparity.Conclusions:This review confirms a strong aetiological link between vaginal birth and POP, with the first vaginal and forceps delivery being the main determinants.