Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet activation induced by coronary artery stenting may be related to stent design. In a prospective, randomized pilot study of 54 elective patients, platelet activation was analyzed before and at 2 hours, 24 hours, 5 days and 30 days post-implantation of either a closed-cell (NIR) or open-cell (TETRA) stent. Platelet activation was less following NIR implantation as indicated by reduced aggregation to 5 mol adenosine diphosphate at 30 days (32.3 6.1% versus 94.5 18.9%; p = 0.02) and reduced expression of multiple surface markers (log mean fluorescence intensity): at 2 hours, CD 107a (22 13 versus 18 5; p = 0.045); at 24 hours, CD 31 (136 48 versus 110 48; p = 0.04), CD 151 (104 45 versus 91 31; p = 0.048), platelet leukocyte aggregates (95 40 versus 77 24; p = 0.018), and CD 107a (24 12 versus 17 4; p = 0.03); and at 30 days, CD 151 (99 33 versus 81 32; p = 0.03), platelet leukocyte aggregates (84 35 versus 72 31; p = 0.045) and PAC-1 (88 91 versus 72 30; p = 0.025). Ex vivo studies in explanted swine hearts revealed that the NIR stent produced less intimal prolapse and thus a smoother stent-vessel wall interface than the TETRA stent. In this pilot study, platelet activation was greater during the 30 days following implantation of an open-cell versus a closed-cell stent. This finding may be related to superior scaffolding, resulting in a smoother luminal contour after implantation of a closed-cell stent.
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PMID:Could stent design affect platelet activation? Results of the Platelet Activation in STenting (PAST) Study. 1236 10

The F(o)F(1)-ATPase, a multisubunit protein complex of the inner mitochondrial membrane, produces most of the ATP in mammalian cells. Mitochondrial diseases as a result of a dysfunction of ATPase can be caused by mutations in mitochondrial DNA-encoded ATPase subunit a or rarely by an ATPase defect of nuclear origin. Here we present a detailed functional and immunochemical analysis of a new case of selective and generalized ATPase deficiency found in an Austrian patient. The defect manifested with developmental delay, muscle hypotonia, failure to thrive, ptosis, and varying lactic acidemia (up to 12 mmol/L) beginning from the neonatal period. A low-degree dilated cardiomyopathy of the left ventricle developed between the age of 1 and 2 y. A >90% decrease in oligomycin-sensitive ATPase activity and an 86% decrease in the content of the ATPase complex was found in muscle mitochondria. It was associated with a significant decrease of ADP-stimulated respiration of succinate (1.5-fold) and respiratory control with ADP (1.7-fold) in permeabilized muscle fibers, and with a slight decrease of the respiratory chain complex I and compensatory increase in the content of complexes III and IV. The same ATPase deficiency without an increase in respiratory chain complexes was found in fibroblasts, suggesting a generalized defect with tissue-specific manifestation. Absence of any mutations in mitochondrial ATP6 and ATP8 genes indicates a nuclear origin of the defect.
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PMID:Reduced respiratory control with ADP and changed pattern of respiratory chain enzymes as a result of selective deficiency of the mitochondrial ATP synthase. 1515 67

Mitochondrial myopathy, associated with muscle weakness and progressive external ophthalmoplegia, is caused by mutations in mitochondria oxidative phosphorylation genes including the heart-muscle isoform of the mitochondrial adenine nucleotide translocator (ANT1). To develop therapies for mitochondrial disease, we have prepared a recombinant adeno-associated viral vector (rAAV) carrying the mouse Ant1 cDNA. This vector has been used to transduce muscle cells and muscle from Ant1 mutant mice, which manifest mitochondrial myopathy. AAV-ANT1 transduction resulted in long-term, stable expression of the Ant1 transgene in muscle precursor cells as well as differentiated muscle fibers. The transgene ANT1 protein was targeted to the mitochondrion, was inserted into the mitochondrial inner membrane, formed a functional ADP/ATP carrier, increased the mitochondrial export of ATP and reversed the histopathological changes associated with the mitochondrial myopathy. Thus, AAV transduction has the potential of providing symptomatic relief for the ophthalmoplegia and ptosis resulting from paralysis of the extraocular eye muscles cause by mutations in the Ant1 gene.
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PMID:Adeno-associated virus-mediated gene transfer of the heart/muscle adenine nucleotide translocator (ANT) in mouse. 1564 64

Mutations in the heart and muscle isoform of adenine nucleotide translocator 1 (ANT1) are associated with autosomal-dominant progressive external opthalmoplegia (adPEO) clinically characterized by exercise intolerance, ptosis and muscle weakness. The pathogenic mechanisms underlying the mitochondrial myopathy caused by ANT1 mutations remain largely unknown. In yeast, expression of ANT1 carrying mutations corresponding to the human adPEO ones causes a wide range of mitochondrial abnormalities. However, functional studies of ANT1 mutations in mammalian cells are lacking, because they have been hindered by the fact that ANT1 expression leads to apoptotic cell death in commonly utilized replicating cell lines. Here, we successfully express functional ANT1 in differentiated mouse myotubes, which naturally contain high levels of ANT1, without causing cell death. We demonstrate, for the first time in these disease-relevant mammalian cells, that mutant human ANT1 causes dominant mitochondrial defects characterized by decreased ADP-ATP exchange function and abnormal translocator reversal potential. These abnormalities are not due to ANT1 loss of function, because knocking down Ant1 in myotubes causes functional changes different from ANT1 mutants. Under certain physiological conditions, mitochondria consume ATP to maintain membrane potential by reversing the ADP-ATP transport. The modified properties of mutant ANT1 can be responsible for disease pathogenesis in adPEO, because exchange reversal occurring at higher than normal membrane potential can cause excessive energy depletion and nucleotide imbalance in ANT1 mutant muscle cells.
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PMID:adPEO mutations in ANT1 impair ADP-ATP translocation in muscle mitochondria. 2158 54

Depressive disorder will be the second highest disease burden worldwide, which will impair life quality, reduce productivity, and increase disability and mortality. Lycium barbarum. polysaccharide (LBP) is the main active fraction purified from Lycium barbarum. The aim of this study was to evaluate the potential therapeutic effects of LBP on depressive mice induced by reserpine, as well as the relevant mechanisms. The antidepressant effect of LBP was investigated by open field test (OFT), forced swimming test (FST), tail suspension test (TST), and antagonism of reserpine hypothermia and ptosis in mice. In addition, we examined the oxidative status and antioxidation power of striatum in both control and depressive mice with or without LBP treatment. To explore the mechanism of LBP on regulating antioxidants in the depressive mice, we detected the expression level of Bcl-2 and poly (ADP ribose) polymerase (PARP) in striatum of mice by western blotting. The results showed that administration with LBP for 4 consecutive weeks significantly increased locomotor activity, reduced the duration of immobility, and antagonized hypothermia and ptosis in mice induced by reserpine. Also, LBP treatment was able to reduce the lipid peroxidation (LPO) production, and enhance the antioxidation effect of the striatum in depressive mice. Furthermore, LBP inhibited the decreased extent of the apoptotic suppressors, Bcl-2 and PARP, which were markedly decreased after treatment with reserpine. The above results indicated that LBP possess antidepressant activities, probably via its powerful antioxidative properties and then decreased the apoptosis of striatum neuron.
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PMID:Improving Activity of Lycium Barbarum. Polysaccharide on Depressive Mice Induced by Reserpine. 3264 63