Association between degenerative aortic valve disease and long-term exposure to cardiovascular risk factors: results of the longitudinal population-based KORA/MONICA survey

Degenerative aortic valve disease (DAVD), a common finding in the elderly, is associated with an increased risk of death due to cardiovascular causes. Taking advantage of its longitudinal design, this study evaluates the prevalence of DAVD and its temporal associations with long-term exposure to cardiovascular risk factors in the general population. We studied 953 subjects (aged 25-74 years) from a random sample of German residents. Risk factors had been determined at a baseline investigation in 1994/95. At a follow-up investigation, 10 years later, standardized echocardiography determined aortic valve morphology and aortic valve area (AVA) as well as left ventricular geometry and function. At the follow-up study, the overall prevalence of DAVD was 28%. In logistic regression models adjusting for traditional cardiovascular risk factors at baseline age (OR 2.0 [1.7-2.3] per 10 years, P < 0.001), active smoking (OR 1.7 [1.1-2.4], P = 0.009) and elevated total cholesterol levels (OR 1.2 [1.1-1.3] per increase of 20 mg/dL, P < 0.001) were significantly related to DAVD at follow-up. Furthermore, age, baseline status of smoking, and total cholesterol level were significant predictors of a smaller AVA at follow-up study. In contrast, hypertension and obesity had no detectable relationship with long-term changes of aortic valve structure. In the general population we observed a high prevalence of DAVD that is associated with long-term exposure to elevated cholesterol levels and active smoking. These findings strengthen the notion that smoking cessation and cholesterol lowering are promising treatment targets for prevention of DAVD.

Simplified criteria for the diagnosis of autoimmune hepatitis

Diagnosis of autoimmune hepatitis (AIH) may be challenging. However, early diagnosis is important because immunosuppression is life-saving. Diagnostic criteria of the International Autoimmune Hepatitis Group (IAIHG) were complex and purely meant for scientific purposes. This study of the IAIHG aims to define simplified diagnostic criteria for routine clinical practice. Candidate criteria included sex, age, autoantibodies, immunoglobutins, absence of viral hepatitis, and histology. The training set included 250 AIH patients and 193 controls from 11 centers worldwide. Scores were built from variables showing predictive ability in univariate analysis. Diagnostic value of each score was assessed by the area under the receiver operating characteristic (ROC) curve. The best score was validated using data of an additional 109 AIH patients and 284 controls. This score included autoantibodies, immunoglobulin G, histology, and exclusion of viral hepatitis. The area under the curve for prediction of AIH was 0.946 in the training set and 0.91 in the validation set. Based on the ROC curves, two cutoff points were chosen. The score was found to have 88% sensitivity and 97% specificity (cutoff >= 6) and 81% sensitivity and 99% specificity (cutoff 2:7) in the validation set. Conclusion: A reliable diagnosis of AIH can be made using a very simple diagnostic score. We propose the diagnosis of probable AIH at a cutoff point greater than 6 points and definite AIH 7 points or higher.

Stem cell transplants for patients with relapsed/refractory leukaemia

Purpose of review Today the indication for allogeneic stem cell transplantation for a high-risk leukaemia in first remission is well defined by most centres. In patients with primary refractory leukaemia the indication is controversially discussed. Similarly patients with relapse and advanced disease have a poor prognosis with chemotherapy, but also with transplantation. Finally more elderly patients with comorbidities seek help from transplantation, most of them in advanced and otherwise refractory disease. The results are reviewed. Recent findings The role of alloimmunity in the control of leukaemia has been defined and pretransplant conditioning treatment could be reduced to less intensive protocols. Graft-versus-leukaemia reactions have been demonstrated with the transfusion of donor lymphocytes. Using nonmyeloablative regimens allogeneic stem cell transplantation could be offered to elderly patients, the majority of patients with acute myeloid leukaemia and myelodysplastic syndromes. The use of antibodies and radio-immunotherapy has improved the treatment of lymphoid malignancies. Cord blood transplants have shown improved results with double transplants. The superiority of maternal donors indicates a role of the donor`s immune repertoire. Summary Taking advantage of alloimmune reactions and reduced intensity conditioning allogeneic stem cell transplantation has become successful even in elderly and fragile patients. The combination of molecular monitoring, targeted therapy and transplantation as a form of immunotherapy may improve the results of leukaemia treatment further.

Novel Pathogenic Mutations and Copy Number Variations in the VPS13A Gene in Patients With Chorea-Acanthocytosis

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene that encodes chorein. It is characterized by adult-onset chorea, peripheral acanthocytes, and neuropsychiatric symptoms. In the present study, we performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis, of the VPS13A gene in ChAc patients. All 73 exons and flanking regions of VPS13A were sequenced in 35 patients diagnosed with ChAc. To detect CNVs, we also performed real-time quantitative PCR and long-range PCR analyses for the VPS13A gene on patients in whom only a single heterozygous mutation was detected. We identified 36 pathogenic mutations, 20 of which were previously unreported, including two novel CNVs. In addition, we investigated the expression of chorein in 16 patients by Western blotting of erythrocyte ghosts. This demonstrated the complete absence of chorein in patients with pathogenic mutations. This comprehensive screen provides an accurate and useful method for the molecular diagnosis of ChAc. (C) 2011 Wiley-Liss, Inc.

Ethanol and gene expression in brain

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Izuru Matusmoto and Peter A. Wilce. The presentations were (1) GABA receptor subunit expression in the human alcoholic brain, by Tracey Buckley and Peter Dodd; (2) NMDAR gene expression during ethanol addiction, by Jorg Puzke, Rainer Spanagel, Walther Zieglgansberger, and Gerald Wolf; (3) Differentially expressed gene in the nucleus accumbens from ethanol-administered rat, by Shuangying Leng; (4) Expression of a novel gene in the alcoholic brain, by Peter A. Wilce; and (5) Investigations of haplotypes of the dopamine Da-receptor gene in alcoholics, by Hans Rommelspacher, Ulrich Finckh, and Lutz G. Schmidt.

Antigenicity and immunogenicity of novel chimeric hepatitis B surface antigen particles with exposed hepatitis C virus epitopes

The small envelope protein of hepatitis B virus (HBsAg-S) can self-assemble into highly organized virus like particles (VLPs) and induce an effective immune response. In this study, a restriction enzyme site was engineered into the cDNA of HBsAg-S at a position corresponding to the exposed site within the hydrophilic a determinant region (amino acid [aa] 127-128) to create a novel HBsAg vaccine vector allowing surface orientation of the inserted sequence. We inserted sequences of various lengths from hypervariable region 1 (HVR1) of the hepatitis C virus (HCV) E2 protein containing immunodominant epitopes and demonstrated secretion of the recombinant HBsAg VLPs from transfected mammalian cells. A number of different recombinant proteins were synthesized, and HBsAg VLPs containing inserts up to 36 aa were secreted with an efficiency similar to that of wild-type HBsAg. The HVR1 region exposed on the particles retained an antigenic structure similar to that recognized immunologically during natural infection. VLPs containing epitopes from either HCV-1a or -1b strains were produced that induced strain-specific antibody responses in immunized mice. Injection of a combination of these VLPs induced antibodies against both HVR1 epitopes that resulted in higher titers than were achieved by vaccination with the individual VLPs, suggesting a synergistic effect. This may lead to the development of recombinant particles which are able to induce a broad anti-HCV immune response against the HCV quasispecies or other quasispecies-like infectious agents.

Duck hepatitis B virus expresses a regulatory HBx-like protein from a hidden open reading frame

Duck hepatitis B viruses (DHBV), unlike mammalian hepadnaviruses, are thought to lack X genes, which encode transcription-regulatory proteins believed to contribute to the development of hepatocellular carcinoma. A lack of association of chronic DHBV infection with hepatocellular carcinoma development supports this belief. Here, we demonstrate that DHBV genomes have a hidden open reading frame from which a transcription-regulatory protein, designated DHBx, is expressed both in vitro and in vivo. We show that DHBx enhances neither viral protein expression, intracellular DNA synthesis, nor virion production when assayed in the full-length genome context in LMH cells. However, similar to mammalian hepadnavirus X proteins, DHBx activates cellular and viral promoters via the Raf-mitogen-activated protein kinase signaling pathway and localizes primarily in the cytoplasm. The functional similarities as,well as the weak sequence homologies of DHBx and the X proteins of mammalian hepadnaviruses strongly suggest a common ancestry of ortho- and avihepadnavirus X genes. In addition, our data disclose similar intracellular localization and transcription regulatory functions of the corresponding proteins, raise new questions as to their presumed role in hepatocarcinogenesis, and imply unique opportunities for deciphering of their still-enigmatic in vivo functions.

Modern scientific methods and their potential in wastewater science and technology

Application of novel analytical and investigative methods such as fluorescence in situ hybridization, confocal laser scanning microscopy (CLSM), microelectrodes and advanced numerical simulation has led to new insights into micro-and macroscopic processes in bioreactors. However, the question is still open whether or not these new findings and the subsequent gain of knowledge are of significant practical relevance and if so, where and how. To find suitable answers it is necessary for engineers to know what can be expected by applying these modern analytical tools. Similarly, scientists could benefit significantly from an intensive dialogue with engineers in order to find out about practical problems and conditions existing in wastewater treatment systems. In this paper, an attempt is made to help bridge the gap between science and engineering in biological wastewater treatment. We provide an overview of recently developed methods in microbiology and in mathematical modeling and numerical simulation. A questionnaire is presented which may help generate a platform from which further technical and scientific developments can be accomplished. Both the paper and the questionnaire are aimed at encouraging scientists and engineers to enter into an intensive, mutually beneficial dialogue. (C) 2002 Elsevier Science Ltd. All rights reserved.

Adoption and maintenance of contour bunds and hedgerows in a dynamic environment - Experience in the Philippine uplands

The widespread adoption of soil conservation technologies by farmers (notably contour hedgerows) observed in Guba, Cebu City, Philippines, is not often observed elsewhere In the country. Adoption of these technologies was because of the interaction of such phenomena as site-specific factors, appropriate extension systems, and technologies. However, lack of hedgerow maintenance, decreasing hedgerow quality, and disappearance of hedgerows raised concerns about sustainability. The dynamic nature of upland farming systems suggests the need for a location-specific farming system development framework, which provides farmers with ongoing extension for continual promotion of appropriate conservation practices.

Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators

The recent identification of several additional members of the family of sugar transport facilitators (gene symbol SLC2A, protein symbol GLUT) has created a heterogeneous and, in part, confusing nomenclature. Therefore, this letter provides a summary of the family members and suggests a systematic nomenclature for SLC2A and GLUT symbols.