965-48 Ejection Fraction and Wall Thickness Correlate with Impaired Energy Metabolism in Patients with Dilated Cardiomyopathy

Using 31P-MR spectroscopy, abnormalities of cardiac energy metabolism have been demonstrated in patients with dilated cardiomyopathy (DCM). However. a detailed analysis of the correlations among energy metabolism, cardiac hemodynamics and myocardial hypertrophy obtained from 31P-MR, right and left heart catheterization and echocardiography has not been presented, 23 patients with DCM (left ventricular (LV) EF 34±3%; NYHA class 2.7±0.1; SE) underwent right and left heart catheterization and echocardiography±3 days before/after MR spectroscopy. Coronary artery disease was ruled out by coronary angiography. ECG-triggered. localized 31 P-MR spectra from the anteroseptal myocardium were acquired at rest (prone position) during 30min on a 1.5 T Philips Gyroscan MR system using ISIS localization, adiabatic pulses. and a 15 sec repetition time. Peak areas were corrected for T1 effects and for blood contamination. and were determined with Lorentzian line fits in the time domain. Linear correlations between creatine phosphate (CP)/ATP ratios and hemodynamic parameters were calculated.LV pressures and diameters. cardiac output, stroke volume, pulmonary arterial pressures, right atrial pressure and pulmonary arterial oxygen saturation did not correlate with CP/ATP. Thus, our data demonstrate that in DCM, the extent of high-energy phosphate depletion is related to the extent of mechanical dysfunction as well as to LV wall thickness

Fibroblast activation protein is expressed by rheumatoid myofibroblast-like synoviocytes

Fibroblast activation protein (FAP), as described so far, is a type II cell surface serine protease expressed by fibroblastic cells in areas of active tissue remodelling such as tumour stroma or healing wounds. We investigated the expression of FAP by fibroblast-like synoviocytes (FLSs) and compared the synovial expression pattern in rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Synovial tissue from diseased joints of 20 patients, 10 patients with refractory RA and 10 patients with end-stage OA, was collected during routine surgery. As a result, FLSs from intensively inflamed synovial tissues of refractory RA expressed FAP at high density. Moreover, FAP expression was co-localised with matrix metalloproteinases (MMP-1 and MMP-13) and CD44 splice variants v3 and v7/8 known to play a major role in the concert of extracellular matrix degradation. The pattern of signals appeared to constitute a characteristic feature of FLSs involved in rheumatoid arthritic joint-destructive processes. These FAP-expressing FLSs with a phenotype of smooth muscle actin-positive myofibroblasts were located in the lining layer of the synovium and differ distinctly from Thy-1-expressing and non-proliferating fibroblasts of the articular matrix. The intensity of FAP-specific staining in synovial tissue from patients with RA was found to be different when compared with end-stage OA. Because expression of FAP by RA FLSs has not been described before, the findings of this study highlight a novel element in cartilage and bone destruction of arthritic joints. Moreover, the specific expression pattern qualifies FAP as a therapeutic target for inhibiting the destructive potential of fibroblast-like synovial cells

Advanced gallbladder inflammation is a risk factor for gallbladder perforation in patients with acute cholecystitis

Abstract Background Acute perforated cholecystitis (APC) is probably the most severe benign gallbladder pathology with high rates of morbidity and mortality. The cause of APC has not been fully understood. We postulated that APC is a complication of advanced gallbladder inflammation. The aim of this study was to investigate the extent of gallbladder inflammation in patients with APC. Methods Patients with intraoperative and histopathologic diagnosis of APC were compared with cases with acute cholecystitis without perforation with respect to the extent of inflammation on histopathology as well as surgical outcomes. Results Fifty patients with APC were compared to 150 cases without perforation. Advanced age > 65 years and elevated CRP were confirmed on multivariate analysis as independent risk factors for APC. Advanced gallbladder inflammation was seen significantly more often in patients with APC (84.0 vs. 18.7%). Surgery lasted significantly longer 131.3 ± 55.2 min vs. 100.4 ± 47.9 min; the rates of conversion (22 vs. 4%), morbidity (24 vs. 7%), and mortality (8 vs. 1%) were significantly higher in patients with APC. ICU management following surgery was needed significantly more often in the APC group (56 vs. 15%), and the overall length of stay (11.2 ± 12.0 days vs. 5.8 ± 6.5 days) was significantly longer compared to the group without perforation. Conclusion Acute gallbladder perforation in patients with acute cholecystitis represents the most severe complication of cholecystitis. Acute perforated cholecystitis is a sequela of advanced gallbladder inflammation like empyematous and gangrenous cholecystitis and is associated with poor outcome compared to non-perforated cases

SLC19A3 Loss-of-Function Variant in Yorkshire Terriers with Leigh-Like Subacute Necrotizing Encephalopathy

Sporadic occurrence of juvenile-onset necrotizing encephalopathy (SNE) has been previously reported in Yorkshire terriers. However, so far, no causative genetic variant has been found for this breed-specific form of suspected mitochondrial encephalomyopathy. Affected dogs showed gait abnormalities, central visual defects, and/or seizures. Histopathological analysis revealed the presence of major characteristics of human Leigh syndrome and SNE in Alaskan huskies. The aim of this study was to characterize the genetic etiology of SNE-affected purebred Yorkshire terriers. After SNP genotyping and subsequent homozygosity mapping, we identified a single loss-of-function variant by whole-genome sequencing in the canine SLC19A3 gene situated in a 1.7 Mb region of homozygosity on chromosome 25. All ten cases were homozygous carriers of a mutant allele, an indel variant in exon 2, that is predicted to lead to a frameshift and to truncate about 86% of the wild type coding sequence. This study reports a most likely pathogenic variant in SLC19A3 causing a form of SNE in Yorkshire terriers and enables selection against this fatal neurodegenerative recessive disorder. This is the second report of a pathogenic alteration of the SLC19A3 gene in dogs with SNE

Comparative genomic hybridisation and ultrafast pyrosequencing revealed remarkable differences between the Sinorhizobium meliloti genomes of the model strain Rm1021 and the field isolate SM11

Stiens M, Becker A, Bekel T, et al. Comparative genomic hybridisation and ultrafast pyrosequencing revealed remarkable differences between the Sinorhizobium meliloti genomes of the model strain Rm1021 and the field isolate SM11. Journal of Biotechnology. 2008;136(1-2):31-37

Morfologia de células murais da granulosa e do cumulus oophorus

Existem diferenças entre a morfologia das células somáticas que constituem o folículo ovariano. As células murais da granulosa e do cumulus oophorus foram coletadas de pacientes que realizaram tratamento de Reprodução Assistida no Núcleo de Reprodução Humana Gerar e foram cultivadas, por 5 dias, no Laboratório de Ginecologia e Obstetrícia Molecular do Hospital de Clínicas de Porto Alegre. Como ilustrado na Figura, as células murais apresentam morfologia alongada, são uninucleadas com bordos delimitados e proliferam em clusters (grumos de células)

Vimentin 3, the new hope, differentiating RCC versus oncocytoma

Vimentin is currently used to differentiate between malignant renal carcinomas and benign oncocytomas. Recent reports showing Vimentin positive oncocytomas seriously question the validity of this present diagnostic approach. Vimentin 3 is a spliced variant and ends with a unique C-terminal ending after exon 7 which differentiates it from the full length version that has 9 exons. Therefore, the protein size is different; the full length Vimentin version has a protein size of ~57 kDa and the truncated version of ~47 kDa. We designed an antibody, called Vim3, against the unique C-terminal ending of the Vimentin 3 variant. Using immune histology, immune fluorescence, Western blot, and qRT-PCR analysis, a Vim3 overexpression was detectable exclusively in oncocytoma, making the detection of Vim3 a potential specific marker for benign kidney tumors. This antibody is the first to clearly differentiate benign oncocytoma and the mimicking eosinophilic variants of the RCCs. This differentiation between malignant and benign RCCs is essential for operative planning, follow-up therapy, and patients' survival. In the future the usage of Vimentin antibodies in routine pathology has to be applied with care. Consideration must be given to Vimentin specific binding epitopes otherwise a misdiagnosis of the patients' tumor samples may result