Two-dimensional echocardiographic localization of residual atrial shunts after the Senning procedure.
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This study sought to determine if areas of late gadolinium enhancement (LGE) would be present in adults with systemic right ventricles and if LGE would be associated with markers of adverse outcomes. Using gadolinium-enhanced magnetic resonance and cardiopulmonary exercise testing, 34 adults with systemic right ventricles (23 patients with atrial repair for transposition of the great arteries and 11 with congenitally corrected transposition) were studied at a mean age of 25 years. LGE was present in 14 patients (41%). The presence of LGE was associated with older age (p = 0.037), a lower right ventricular (RV) ejection fraction (34% vs 45%, p = 0.006), higher RV wall stress (p = 0.0001), reduced peak oxygen uptake (47% vs 56%, p = 0.001), and a history of arrhythmia (p = 0.005). The RV ejection fraction was correlated with RV wall stress (r = -0.81, p <0.0001) and peak oxygen uptake (r = 0.74, p <0.0001). Twelve patients experienced worsening of their clinical conditions. This was associated with decreases in biventricular function and increases in the prevalence and number of LGE areas. In conclusion, patients with systemic right ventricles have areas of abnormal myocardium, presumably due to fibrosis, that can be seen by contrast-enhanced magnetic resonance imaging. The presence of abnormal myocardial regions is associated with RV dysfunction, poor exercise tolerance, arrhythmia, and progressive clinical deterioration.
OBJECTIVES: To determine the prevalence of SENV infections among blood donors in central Taiwan and to clarify the relationship between these infections and elevated alanine aminotransaminase (ALT) values. METHODS: DNA was extracted from plasma of 200 blood donors and amplified by seminested PCR. RESULTS: For all donors, the prevalence of SENV-D was 32%, and of SENV-H was 30.5%. Prevalence of mixed SENV-D/H infection was 11.5% and of SENV-D and/or SENV-H (SENV-D/H) was 51%. Infections were not associated with age, gender, or raised ALT values. CONCLUSIONS: SENV-D and SENV-H infections are common among blood donors in central Taiwan but are unlikely to contribute to abnormal ALT values.
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We have identified a small, highly structured (shs)RNA that binds human recombinant prion protein (hrPrP) with high affinity and specificity under physiological conditions (e.g. 10% bovine calf serum (BCS), neutral pH, nanomolar concentrations of RNA and hrPrP). We also demonstrate the ability of this shsRNA to form highly stable nucleoprotein complexes with hrPrP and cellular PrP (PrP(C)) from various cell extracts and mammalian brain homogenates. The apparent mass of the nucleoprotein complex is dependent on the molar ratio of hrPrP to RNA during complex formation. The hrPrP in these complexes acquires resistance to degradation by Proteinase K (PK). Other shsRNAs, however, under identical conditions, neither form stable complexes with hrPrP nor do they induce resistance to PK digestion. We also demonstrate that the RNAs in these nucleoprotein complexes become resistant to ribonuclease A hydrolysis. These interactions between shsRNAs and hrPrP suggest possible roles of RNAs in the modulation of PrP structure and perhaps disease development. ShsRNAs that bind to hrPrP with high affinity and induce resistance to PK digestion can be used to develop molecular biology assays for the screening of compounds associated with PrP structure transformation or for drugs that inhibit this process.
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Conversion of the PrP cellular form (PrP(C)) to the pathogenic form (PrP(Sc)) is the key step in the pathogenesis of transmissible spongiform encephalophathies. Although the mechanism of conformational conversion of PrP proteins remains uncertain, the cell-free conversion reaction and other in vitro PrP amplification tests allow it to be studied under the much quicker and simpler conditions than those of transmission bioassay in vivo. Using baculovirus expression system, wild-type hamster (HaPrP) and human PrP (HuPrP), as well as D178N mutated human PrP (HuPrPm178) were expressed in HIS-fusion form. After 35S-methionine labeling and purification with Ni-NTA agarose affinity chromatography, individual expressed PrP proteins were mixed with PrP(Sc) isolated from hamster brain tissue infected with scrapie 263K. Protease-resistant isoform was detected in the homologous HaPrP reaction, but not in the two heterologous HuPrP preparations, implying a species-specific molecular recognition between PrP(C) and PrP(Sc). HIS-tag in HIS-HaPrP seems to have little effect on the formation of protease-resistant protein in this preparation. This system proposes a simple and protein productive-enriched way for cell-free conversion of prion proteins, as the replacement of native or genetic engineering expressed sole PrP(C) from mammalian or non-mammalian sources.
Gosha-jinki-gan (GJG) is a Chinese herbal medicine that is known to be useful for the treatment of diabetic neuropathy. In the present study, the effect of GJG on insulin resistance in streptozotocin (STZ, 50 mgkg(-1) BW, i.v.) -induced diabetic rats was examined by means of the euglycemic clamp procedure. To accomplish this objective, diabetic and non-diabetic control rats were divided as follows: a single dose administration of GJG (800 mgkg(-1) BW, p.o.), saline (5 mlkg(-1) BW, p.o.), and GJG (p.o)+N(G)-monomethyl-L-arginine (L-NMMA, 1 mgkg(-1)min(-1) BW, i.v.). In diabetic rats, the incremental area (DeltaAUC [area under curve]) of the glucose metabolic clearance rate (MCR) during a 3.0 mUkg(-1)min(-1) insulin infusion rate was significantly higher in the GJG-administrated group compared to the saline-administrated one. On the other hand, the effect of GJG on the DeltaAUC of MCR in diabetic rats was abolished by L-NMMA. In addition, no significant differences in the DeltaAUC of MCR were observed in non-diabetic control rats. These results suggest that a single dose administration of GJG can improve the glucose utilization and insulin resistance in STZ-induced diabetic rats, probably via the nitric oxide (NO) pathway.
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