Search results for "Metabolic disease"
showing 10 items of 778 documents
Phosphorylation of mismatch repair proteins MSH2 and MSH6 affecting MutSα mismatch-binding activity
2002
Mismatch repair (MMR) is involved in the removal of mispaired bases from DNA and thus plays an important role in the maintenance of genomic stability and the prevention of mutations and cancer. Moreover, MMR triggers genotoxicity and apoptosis upon processing of DNA lesions such as O6-methylguanine. Whereas the enzymology of MMR has been elucidated in great detail, only limited data are available concerning its regulation. Here we show that the major mismatch-binding proteins MSH2 and MSH6, forming the MutSalpha complex, are phosphorylated in vitro by protein kinase C and casein kinase II, but not by protein kinase A. Phosphorylation of MSH2 and MSH6 was also found within the cell, with MSH…
Sp1 transcription factor interaction with accumulated prelamin a impairs adipose lineage differentiation in human mesenchymal stem cells: essential r…
2012
Abstract Lamin A (LMNA)-linked lipodystrophies may be either genetic (associated with LMNA mutations) or acquired (associated with the use of human immunodeficiency virus protease inhibitors [PIs]), and in both cases they share clinical features such as anomalous distribution of body fat or generalized loss of adipose tissue, metabolic alterations, and early cardiovascular complications. Both LMNA-linked lipodystrophies are characterized by the accumulation of the lamin A precursor prelamin A. The pathological mechanism by which prelamin A accumulation induces the lipodystrophy associated phenotypes remains unclear. Since the affected tissues in these disorders are of mesenchymal origin, we…
Studies on the interaction of C1q,a subcomponent of the first component of complement, with porins fromSalmonella minnesotaincorporated into artifici…
1990
AbstractPurified outer membrane proteins (OMP) of Salmonella minnesota, Re-form, were incorporated into liposomes. These induced in macrophages a chemiluminescence signal identical to that of the intact Re-form. This signal was abolished by preincubation of porin-containing liposomes with purified C1q. Incorporation of isolated OMP into black lipid membranes (BLM) resulted in channel-formation which could not be inhibited by isolated C1q. Additionally, incubation of OMP-containing liposomes with BLM resulted in pore-formation within the BLM. This was amplified when lipid A was present within the liposomes. Preincubation of OMP-containing liposomes with purified C1q abolished pore-formation …
Safety of Dietary Guanidinoacetic Acid: A Villain of a Good Guy?
2021
Guanidinoacetic acid (GAA) is a natural amino acid derivative that is well-recognized for its central role in the biosynthesis of creatine, an essential compound involved in cellular energy metabolism. GAA (also known as glycocyamine or betacyamine) has been investigated as an energy-boosting dietary supplement in humans for more than 70 years. GAA is suggested to effectively increase low levels of tissue creatine and improve clinical features of cardiometabolic and neurological diseases, with GAA often outcompeting traditional bioenergetics agents in maintaining ATP status during stress. This perhaps happens due to a favorable delivery of GAA through specific membrane transporters (such as…
Enzyme replacement and gene therapy for mucopolysaccharidoses: current progress and future directions
2015
Introduction: Mucopolysaccharidoses (MPS) are lysosomal storage disorders caused by the deficiency of enzymes that are responsible for the stepwise degradation of complex carbohydrates, the glycosaminoglycans. Whereas in the past the treatment of MPS consisted mainly of palliative care, enzyme replacement therapy (ERT) is now possible for some MPS disorders, and in the future many other therapeutic options will become available.Areas covered: This review, based on personal experience and the currently available literature, will give an overview on the efficacy and limitations of ERT and will discuss new therapeutic approaches, such as anti-inflammatory drugs, substrate reduction therapy, ch…
B and T lymphocytes are affected in lysosomal disorders--an immunoelectron microscopic study.
1991
Circulating lymphocytes of four patients with mucopolysaccharidoses II and IIIA, four patients with juvenile neuronal ceroid-lipofuscinosis, one patient each with glycogenosis type II, infantile neuronal ceroid-lipofuscinosis, and Gaucher disease were classified by immunoelectron microscopy as B or T lymphocytes. Disease-specific lysosomal inclusions as well as non-specific lysosomal organelles, especially Gall bodies were identified in B and T lymphocytes. These non-quantitative studies indicate that both B and T lymphocytes participate in the lysosomal storage process.
Expression of hMLH1 and hMSH2 proteins in ameloblastomas and tooth germs
2017
Background Mismatch repair proteins (MMRPs) are a group of nuclear enzymes that participate in the repair of base mismatches that occur during DNA replication in all proliferating cells. The most studied MMRPs are hMSH2 and hMLH1, which are known to be highly expressed in normal tissues. A loss of MMRPs leads to the accumulation of DNA replication errors in proliferating cells. Ki-67 is a biomarker regarded to be the gold-standard tool for determining cell proliferation by immunohistochemical methods. The aim of this study was to investigate the immunohistochemical expression of hMLH1, hMSH2 and Ki-67 proteins in ameloblastomas and tooth germs, to contribute to the understanding of the deve…
Audiological Findings in Children With Mucopolysaccharidoses Type I–IV
2017
Abstract Objective The aim of our study is to reflect hearing impairment of 23 children diagnosed with mucopolysaccharidosis (MPS) type I, II, III and IV. Methods Retrospective study of the clinical, audiological and treatment (medical vs surgical) findings of 23 children diagnosed with MPS type I, II, III and IV followed at a Tertiary Referral Hospital between 1997 and 2015. Results Six cases of MPS I, 8 of MPS II, 4 of MPS III and 5 of MPS IV were reviewed. 71.2% of patients had secretory otitis media (SOM) and 54% of patients had some type of hearing loss (HL). The behaviour of hearing loss was variable in each of the subgroups of MPS, finding greater involvement and variability in types…
Outcome of patients with classical infantile pompe disease receiving enzyme replacement therapy in Germany
2015
Enzyme replacement therapy (ERT) has been shown to improve outcome in classical infantile Pompe disease. The purpose of this study was to assess mortality, morbidity, and shortcomings of ERT in a larger cohort of patients treated outside clinical trials. To accomplish this, we retrospectively analyzed the data of all 23 subjects with classical infantile Pompe disease having started ERT in Germany between January 2003 and December 2010.Ten patients (43%) deceased and four others (17%) became ventilator dependent. Seven infants (30.5%) made no motor progress at all, while seven (30.5%) achieved free sitting, and nine (39%) gained free walking. Besides all the seven patients (100%) attaining n…
Exciton and multiexciton optical properties of single InAs/GaAs site-controlled quantum dots
2013
We have studied the optical properties of InAs site-controlled quantum dots (SCQDs) grown on pre-patterned GaAs substrates. Since InAs nucleates preferentially on the lithography motifs, the location of the resulting QDs is determined by the pattern, which is fabricated by local oxidation nanolithography. Optical characterization has been performed on such SCQDs to study the fundamental and excited states. At the ground state different exciton complex transitions of about 500 μeV linewidth have been identified and the fine structure splitting of the neutral exciton has been determined (≈65 μeV). The observed electronic structure covers the demands of future quantum information technologies.…