Protein misfolding has been shown to be the direct cause of a number of highly devastating diseases such as Alzheimer's disease, Parkinson's disease, and Creutzfeldt-Jacob syndrome, affecting the aging population globally. The deposition in tissues of amyloid fibrils is a characteristic of all these diseases, and the mechanisms by which these protein aggregates form continue to be intensively investigated. In only a fraction of cases is an underlying mutation responsible, and accordingly, what initiates amyloid formation in vivo is the major question that is addressed. In this study, we show that membranes containing phosphatidylserine (PS), a negatively charged phospholipid, induce a rapid formation of fibers by a variety of proteins, viz., lysozyme, insulin, glyceraldehyde-3-phosphate dehydrogenase, myoglobin, transthyretin, cytochrome c, histone H1, and alpha-lactalbumin. Congo red staining of these fibers yields the characteristic light green birefringence of amyloid, and fluorescent lipid tracers further reveal them to include phospholipids. Our results suggest that PS as well as other acidic phospholipids could provide the physiological low-pH environment on cellular membranes, enhancing protein fibril formation in vivo. Interestingly, all the proteins mentioned above either are cytotoxic or induce apoptosis. PS-protein interaction could be involved in the mechanism of cytotoxicity of the aggregated protein fibrils, perturbing membrane functions. Importantly, our results suggest that this process induced by acidic phospholipids may provide an unprecedented and generic connection between three current major areas of research: (i) mechanism(s) triggering amyloid formation, (ii) cytotoxicity of amyloidal protein aggregates, and (iii) mechanism(s) of action of cytotoxic proteins.
Cone-beam CT technology with new design and flexible gantry movements allows both supine and weight-bearing imaging of the lower extremities, with a reasonable radiation dose and excellent image quality. Weight-bearing CT of joints can provide important new clinical information in musculoskeletal radiology.
We have compared three different methods of treating symptomatic non-traumatic tears of the supraspinatus tendon in patients above 55 years of age. A total of 180 shoulders (173 patients) with supraspinatus tendon tears were randomly allocated into one of three groups (each of 60 shoulders); physiotherapy (group 1), acromioplasty and physiotherapy (group 2) and rotator cuff repair, acromioplasty and physiotherapy (group 3). The Constant score was assessed and followed up by an independent observer pre-operatively and at three, six and twelve months after the intervention. Of these, 167 shoulders were available for assessment at one year (follow-up rate of 92.8%). There were 55 shoulders in group 1 (24 in males and 31 in females, mean age 65 years (55 to 79)), 57 in group 2 (29 male and 28 female, mean age 65 years (55 to 79)) and 55 shoulders in group 3 (26 male and 29 female, mean age 65 years (55 to 81)). There were no between-group differences in the Constant score at final follow-up: 74.1 (sd 14.2), 77.2 (sd 13.0) and 77.9 (sd 12.1) in groups 1, 2 and 3, respectively (p = 0.34). The mean change in the Constant score was 17.0, 17.5, and 19.8, respectively (p = 0.34). These results suggest that at one-year follow-up, operative treatment is no better than conservative treatment with regard to non-traumatic supraspinatus tears, and that conservative treatment should be considered as the primary method of treatment for this condition.
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