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Degenerative Disorders (degenerative + disorders)
Selected AbstractsDetection of carbonyl-modified proteins in interfibrillar rat mitochondria using N, -aminooxymethylcarbonylhydrazino- D -biotin as an aldehyde/keto-reactive probe in combination with Western blot analysis and tandem mass spectrometryELECTROPHORESIS, Issue 6 2008Woon-Gye Chung Abstract There is now a large body of supporting data available that links oxidative modifications of proteins to a large number of diseases, degenerative disorders and aging. However, the detailed analysis of oxidative protein modifications remains challenging. Here, we report a new efficient method for identification of oxidatively modified proteins in complex biological samples which is based on the use of an aldehyde-reactive probe, N,-aminooxymethylcarbonylhydrazino- D -biotin (ARP), in combination with Western-type analyses and MS. The biotinylated hydroxylamine derivative forms a chemically stable oxime derivative with the aldehyde/keto group found in carbonyl-modified proteins. The biotin tag is detected by avidin affinity staining. ARP-positive proteins are subsequently subjected to in-gel trypsinization and MS/MS for protein identification. We demonstrate the usefulness of the method for the analysis of protein extracts obtained from interfibrillar heart mitochondria (IFM) from young and old rats. In this study, we identified as putative major protein targets of oxidative modifications the mitochondrial matrix protein, aconitase, the inner mitochondrial membrane protein, ADP/ATP translocase, and constituents of the electron transport chain complexes IV and V. An age-related increase of carbonyl levels was found for aconitase and ATP synthase. [source] Soluble protein oligomers as emerging toxins in alzheimer's and other amyloid diseasesIUBMB LIFE, Issue 4-5 2007Sergio T. Ferreira Abstract Amyloid diseases are a group of degenerative disorders characterized by cell/tissue damage caused by toxic protein aggregates. Abnormal production, processing and/or clearance of misfolded proteins or peptides may lead to their accumulation and to the formation of amyloid aggregates. Early histopathological investigation of affected organs in different amyloid diseases revealed the ubiquitous presence of fibrillar protein aggregates forming large deposits known as amyloid plaques. Further in vitro biochemical and cell biology studies, as well as studies using transgenic animal models, provided strong support to what initially seemed to be a solid concept, namely that amyloid fibrils played crucial roles in amyloid pathogenesis. However, recent studies describing tissue-specific accumulation of soluble protein oligomers and their strong impact on cell function have challenged the fibril hypothesis and led to the emergence of a new view: Fibrils are not the only toxins derived from amyloidogenic proteins and, quite possibly, not the most important ones with respect to disease etiology. Here, we review some of the recent findings and concepts in this rapidly developing field, with emphasis on the involvement of soluble oligomers of the amyloid-, peptide in the pathogenesis of Alzheimer's disease. Recent studies suggesting that soluble oligomers from different proteins may share common mechanisms of cytotoxicity are also discussed. Increased understanding of the cellular toxic mechanisms triggered by protein oligomers may lead to the development of rational, effective treatments for amyloid disorders. IUBMB Life, 59: 332-345, 2007 [source] Enhancing the mechanical integrity of the implant,bone interface with BoneWelding® technology: Determination of quasi-static interfacial strength and fatigue resistanceJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2006Stephen J. Ferguson Abstract The BoneWelding® technology is an innovative bonding method, which offers new alternatives in the treatment of fractures and other degenerative disorders of the musculoskeletal system. The BoneWelding process employs ultrasonic energy to liquefy a polymeric interface between orthopaedic implants and the host bone. Polymer penetrates the pores of the surrounding bone and, following a rapid solidification, forms a strong and uniform bond between implant and bone. Biomechanical testing was performed to determine the quasi-static push-out strength and fatigue performance of 3.5-mm-diameter polymeric dowels bonded to a bone surrogate material (Sawbones solid and cellular polyurethane foam) using the BoneWelding process. Fatigue tests were conducted over 100,000 cycles of 20,100 N loading. Mechanical test results were compared with those obtained with a comparably-sized, commercial metallic fracture fixation screw. Tests in surrogate bone material of varying density demonstrated significantly superior mechanical performance of the bonded dowels in comparison to conventional bone screws (p < 0.01), with holding strengths approaching 700 N. Even in extremely porous host material, the performance of the bonded dowels was equivalent to that of the bone screws. For both cellular and solid bone analog materials, failure always occurred within the bone analog material surrounding and distant to the implant; the infiltrated interface was stronger than the surrounding bone analog material. No significant decrease in interfacial strength was observed following conditioning in a physiological saline solution for a period of 1 month prior to testing. Ultrasonically inserted implants migrated, on average, less than 20 ,m over, and interfacial stiffness remained constant the full duration of fatigue testing. With further refinement, the BoneWelding technology may offer a quicker, simpler, and more effective method for achieving strong fixation and primary stability for fracture fixation or other orthopaedic and dental implant applications. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006 [source] Brain-Derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4/5 Prevent the Death of Striatal Projection Neurons in a Rodent Model of Huntington's DiseaseJOURNAL OF NEUROCHEMISTRY, Issue 5 2000Esther Pérez-Navarro Abstract: Intrastriatal injection of quinolinate has been proven to be a very useful animal model to study the pathogenesis and treatment of Huntington's disease. To determine whether growth factors of the neurotrophin family are able to prevent the degeneration of striatal projection neurons, cell lines expressing brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4/5 (NT-4/5) were grafted in the adult rat striatum before quinolinate injection. Three days after lesioning, ongoing cell death was assessed by in situ detection of DNA fragmentation. In animals grafted with the control cell line, quinolinate injection induced a gradual cell loss that was differentially prevented by intrastriatal grafting of BDNF-, NT-3-, or NT-4/5-secreting cells. Seven days after lesioning, we characterized striatal projection neurons that were protected by neurotrophins. Quinolinate injection, alone or in combination with the control cell line, induced a selective loss of striatal projection neurons. Grafting of a BDNF-secreting cell line prevented the loss of all types of striatal projection neurons analyzed. Glutamic acid decarboxylase 67-, preproenkephalin-, and preprotachykinin A- but not prodynorphin-expressing neurons were protected by grafting of NT-3- or NT-4/5-secreting cells but with less efficiency than the BDNF-secreting cells. Our findings show that neurotrophins are able to promote the survival of striatal projection neurons in vivo and suggest that BDNF might be beneficial for the treatment of striatonigral degenerative disorders, including Huntington's disease. [source] Induced pluripotent stem cells (iPSCs): the emergence of a new champion in stem cell technology-driven biomedical applicationsJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 6 2010Anjan Kumar Das Abstract Pluripotent stem cells possess the unique property of differentiating into all other cell types of the human body. Further, the discovery of induced pluripotent stem cells (iPSCs) in 2006 has opened up new avenues in clinical medicine. In simple language, iPSCs are nothing but somatic cells reprogrammed genetically to exhibit pluripotent characteristics. This process utilizes retroviruses/lentiviruses/adenovirus/plasmids to incorporate candidate genes into somatic cells isolated from any part of the human body. It is also possible to develop disease-specific iPSCs which are most likely to revolutionize research in respect to the pathophysiology of most debilitating diseases, as these can be mimicked ex vivo in the laboratory. These models can also be used to study the safety and efficacy of known drugs or potential drug candidates for a particular diseased condition, limiting the need for animal studies and considerably reducing the time and money required to develop new drugs. Recently, functional neurons, cardiomyocytes, pancreatic islet cells, hepatocytes and retinal cells have been derived from human iPSCs, thus re-confirming the pluripotency and differentiation capacity of these cells. These findings further open up the possibility of using iPSCs in cell replacement therapy for various degenerative disorders. In this review we highlight the development of iPSCs by different methods, their biological characteristics and their prospective applications in regenerative medicine and drug screening. We further discuss some practical limitations pertaining to this technology and how they can be averted for the betterment of human life. Copyright © 2010 John Wiley & Sons, Ltd. [source] The clinical features and surgical treatment of degenerative lumbar scoliosis: A review of 112 patientsORTHOPAEDIC SURGERY, Issue 3 2009Wei Liu MD Objective:, To investigate the clinical features, radiological characteristics and surgical results of degenerative lumbar scoliosis (DLS). Methods:, One hundred and twelve cases of DLS treated surgically from June 2001 to February 2006 were retrospectively reviewed for clinical features, characteristics of nerve root compression and imaging presentations. According to the preoperative clinical manifestations and imaging findings, different surgical modalities were performed, including simple nerve decompression and decompression with short or long posterior fusion (less or more than three segments, respectively). Results:, The mean age of 47 male and 65 female patients was 54.7 years. Clinical manifestations included lower back pain (76.8%), radiculopathy (79.5%) and claudication (48.2%). Plain lumbar radiograph showed right scoliosis in 87 and left scoliosis in the other 25 cases; the Cobb angle was 10°,46°; the apex of scoliosis mostly located at L3 (48.2%); L3 and L4 nerve roots were usually compressed on the concave side and L5 and S1 nerve roots on the convex side. The Cobb angle and physiologic lordosis angle of patients who underwent multi-segment (>3 segments) fusion improved to a greater extent than did that of patients who had simple decompression without fusion. A mean 5.7-year follow-up showed that the average improvement in Oswestry disability index (ODI) scores was 32.6, 26.3 and 13.5 for long segment fusion, short segment fusion and simple decompression without fusion, respectively. Conclusion:, Decompression surgery with or without fusion, the main purpose of which is to relieve nerve root compression and stabilize the spinal column, is an effective treatment for chronic DLS. The treatment should be individualized according to the patient's age, general and economic factors, severity of deformity and other coexisting lumbar degenerative disorders. [source] Two Subgroups of Stapes Fixation: Otosclerosis and Pseudo-Otosclerosis,THE LARYNGOSCOPE, Issue 11 2005Tamás Karosi MD Abstract Hypothesis: Stapes ankylosis is a disease with variable histopathology and can be caused by otosclerosis or pseudo-otosclerosis. Viral pathogenesis of otosclerosis could be established only by correlative analysis: histologic examination of the stapes footplate and reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of the viral RNA. Background: Presence of the RNA genome of measles virus was demonstrated in the footplates of clinically otosclerotic patients by RT-PCR, and also viral proteins were detected by immunohistochemistry. Methods: Nucleic acids were extracted from ankylotic stapes footplates of clinically stapes fixation patients (n = 104). Measles virus genomic nucleoprotein (NP) RNA was amplified by seminested RT-PCR. Amplification results were correlated to postoperative histologic and audiologic findings. Results: Measles virus RNA was detectable only in histologically otosclerotic stapes footplates (n = 67). Histology for virus negative footplates (n = 37) excluded otosclerosis. Virus negative stapes footplates showed nonotosclerotic, degenerative disorders. Conclusions: Stapes ankylosis is a heterogeneous disease causing conductive hearing loss with different etiologies. Nonotosclerotic stapes fixations could be established as pseudo-otosclerosis and may belong to nonspecific, degenerative disorders with variable and noncharacteristic histopathology. Otosclerosis is an inflammatory disease caused by persisting measles virus infection of the otic cap-sule. [source] Doppler sonographic findings in the long bicipital tendon sheath in patients with rheumatoid arthritis as compared with patients with degenerative diseases of the shoulderARTHRITIS & RHEUMATISM, Issue 7 2003Johannes Strunk Objective To compare power Doppler sonography (PDS) findings inside the bicipital tendon sheath in patients with rheumatoid arthritis (RA) and degenerative disorders of the shoulder, in order to evaluate the diagnostic value of PDS in distinguishing between inflammatory and noninflammatory shoulder pain. Methods The glenohumeral joints of 41 consecutive patients with shoulder pain were examined by ultrasound. Using ventral transverse and longitudinal scanning, the vascularity near and/or inside the bicipital tendon sheath was visualized by PDS. One fully trained and experienced examiner performed the sonography. Representative images were digitally stored and were read, under blinded conditions, by 2 independent investigators, who categorized the Doppler signals as being either inside or outside the tendon sheath. Results Biceps tendon sheath effusion, represented by the typical hypoechoic rim, was found in 95.8% of the RA patients (23 of 24) and in 58.8% of the patients with degenerative disorders (10 of 17). PDS signals were localized to inside the tendon sheath in 22 of the RA patients (91.7%) and in none of the patients with degenerative disorders. Although no PDS signal was found inside the tendon sheath in patients with degenerative disorders, in 9 of these patients (52.9%), signals could be localized to the environment of the tendon sheath. Conclusion PDS demonstrates vascularity in the long bicipital tendon sheath of patients with RA, but not in those with degenerative shoulder disorders. [source] Multiscale modeling of nucleic acids: Insights into DNA flexibilityBIOPOLYMERS, Issue 9 2008Yannick J. Bomble Abstract The elastic rod theory is used together with all-atom normal mode analysis in implicit solvent to characterize the mechanical flexibility of duplex DNA. The bending, twisting, stretching rigidities extracted from all-atom simulations (on linear duplexes from 60 to 150 base pairs in length and from 94-bp minicircles) are in reasonable agreement with experimental results. We focus on salt concentration and sequence effects on the overall flexibility. Bending persistence lengths are about 20% higher than most experimental estimates, but the transition from low-salt to high-salt behavior is reproduced well, as is the dependence of the stretching modulus on salt (which is opposite to that of bending). CTG and CGG trinucleotide repeats, responsible for several degenerative disorders, are found to be more flexible than random DNA, in agreement with several recent studies, whereas poly(dA).poly(dT) is the stiffest sequence we have encountered. The results suggest that current all-atom potentials, which were parameterized on small molecules and short oligonucleotides, also provide a useful description of duplex DNA at much longer length scales. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 722,731, 2008. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] | |||||||||||||