Identification of Cohesive Ends and Genes Encoding the Terminase of Phage 16-3

Cohesive ends of 16-3, a temperate phage of Rhizobium meliloti 41, have been identified as 10-base-long, 3′-protruding complementary G/C-rich sequences. terS and terL encode the two subunits of 16-3 terminase. Significant homologies were detected among the terminase subunits of phage 16-3 and other phages from various ecosystems

Fabry-betegség – terápiás útmutató

A Fabry-kór a lizoszomális tárolási betegségek csoportjába tartozó, X-kromoszómához kötötten, recesszív módon öröklődő betegség, amely a globotriaozilceramid felhalmozódásához vezet a szervezet legkülönbözőbb szöveteiben. A betegség első tünetei többnyire gyermekkorban jelentkeznek, a progresszió során a betegek súlyos szervi károsodásokkal és korai halálozással számolhatnak. Elsősorban férfiak érintettek, azonban a betegség tüneteit heterozigóta nők esetében is megfigyelhetjük, de náluk a kórkép súlyossága változó, általában enyhébb lefolyású. Az enzimpótló kezelések megjelenése szükségessé tette, hogy részletes diagnosztikus és terápiás protokollt dolgozzunk ki. A jelen dolgozatban megjelenő ajánlásokat egy, a magyarországi Fabry-kóros betegek kezelésében részt vevő orvosokból, a diagnosztika területén dolgozó biológosukból és egyéb szakemberekből álló multidiszciplináris munkacsoport foglalta össze. A munkacsoport áttekintette a korábbi klinikai tanulmányokat, a publikált vizsgálatokat és a közelmúltban megjelent nemzetközi és nemzeti útmutatókat. | Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive and the first symptoms usually present in childhood. Consequences of the disease are disability and premature death. The disease in females could be as severe as in males although women may be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline has been summarized by a Hungarian multi-disciplinary working group consisting of physicians who are involved in diagnosis and care of Fabry patients. Previous clinical studies, published articles, and recently established international treatment guidelines were reviewed by the group

Synchronous malignant B-cell lymphoma and gastric tubular adenocarcinoma associated with paraneoplastic cutaneous vasculitis: hypereosinophilic syndrome with mixed cryoglobulinemia is an important sign of paraneoplastic syndrome

Gastric adenocarcinoma developing concomitantly with a lymphoma is rare. Furthermore, B-cell lymphoma, originating from lymph nodes, with eosinophilia is extremely rare. We report here a case with a synchronous diffuse large B-cell lymphoma (DLBCL) and an early adenocarcinoma of the stomach. In addition, this case seemed to be associated with paraneoplastic cutaneous vasculitis caused by hypereosinophilic syndrome (HES) with mixed cryoglobulinemia (MC). Many neoplastic diseases that affect internal organs display cutaneous manifestations, which may be the presenting signs and symptoms of the underlying malignancy. In particular, the association between cutaneous vasculitis and malignancy has been widely reviewed, and recently neoplasms have been suggested to produce antigens and the resultant immune complex formations, activating the serum complement, thus cause paraneoplastic vasculitis. In this case, severe eosinophilia and cryoglobulinemia with low complements were observed in a laboratory test. A biopsy specimen from a skin lesion revealed leukocytoclastic vasculitis with severe perivascular infiltration of eosinophils. The cutaneous vasuculitis was considered to be a manifestation of HES with MC, although there were no etiological factors of HES and MC. Therefore, the vasculitis seems to be a symptom of paraneoplastic syndrome in this case. Our finding suggests that the potential presence of malignancies should be kept in mind as a possible underlying disorder especially in the presence of HES with MC; this possibility is interesting also as regards at least part of the pathogenesis for paraneplastic syndrome

Fabry-betegség - Diagnosztikai útmutató

A Fabry-kór a lizoszomális tárolási betegségek csoportjába tartozó, X-kromoszómához kötötten, recesszív módon öröklődő betegség, amely a globotriaosylceramid felhalmozódásához vezet a szervezet legkülönbözőbb szöveteiben. A betegség első tünetei többnyire gyermekkorban jelentkeznek, a progresszió során a betegek súlyos szervi károsodásokkal és korai halálozással számolhatnak. Elsősorban fiúk és férfiak érintettek, azonban a betegség tüneteit heterozigóta nők esetében is megfigyelhetjük, de náluk a kórkép súlyossága változó, általában enyhébb lefolyású. Az enzimpótló kezelések megjelenése szükségessé tette, hogy részletes diagnosztikus és terápiás protokollt dolgozzunk ki. A jelen dolgozatban megjelenő ajánlásokat egy, a magyarországi Fabry-betegek kezelésében aktívan részt vevő orvosokból, a diagnosztika területén dolgozó biológosukból és egyéb szakemberekből álló multidiszciplináris munkacsoport foglalta össze. A munkacsoport áttekintette a korábbi klinikai tanulmányokat, a publikált vizsgálatokat és a közelmúltban megjelent nemzetközi és nemzeti útmutatókat. | Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive, first symptoms usually present in childhood. Consequencies of the diseases are disability and premature death. The disease in females could be as severe as in males although women may also be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline was established by a Hungarian multi-disciplinary working group, consisting of physicians who are involved in health care of Fabry patients. Previous clinical studies, published materials, and recently established international treatment guidelines were reviewed by the group

Note on the special fillet fatty acid composition of the dwarf carp (Cyprinus carpio carpio) living in thermal Lake Hévíz, Hungary

Fatty acid (FA) composition of the fillet and the intestinal content of dwarf common carp (Cyprinus carpio carpio) living in Lake Hévíz was determined in wintertime collected samples and results were compared to widespread literature data on carp. Fillet FA profile of the thermally adapted (28 oC) Hévíz dwarf carps differed from profiles originated from divergent culture and feeding conditions in the overall level of saturation. Fillet myristic acid proportions largely exceeded all literature data in spite of poor dietary supply. Fillet fatty acid results indicate the effects of thermal adaptation (high saturation level) and the correlative effects of feed components rich in omega-3 fatty acids, with special respect to docosahexaenoic acid. With the application of discriminant factor analysis the Hévíz sample was accurately differentiated from the literature data on carp fillet fatty acid profile, mostly based on C14:0, C18:1 n9, C18:2 n6, C20:1 n9 and C20:4 n6 FAs. In summary, fillet FA profile suggested thermal adaptation, location specificity and the ingestion of algal and bacterial material

Impact of Dreissena fouling on the physiological condition of native and invasive bivalves : interspecific and temporal variations

The impact of Dreissena fouling on unionids has hardly been studied in Europe, despite the fact that in some ecosystems (e.g. Lake Balaton, Hungary) infestations of several hundreds to a thousand individuals per unionid have been observed. At present, the zebra mussel Dreissena polymorpha is a dominant species in Lake Balaton and in the last decade three other invasive bivalves were introduced, potentially increasing the pressure on native unionid survival. We examined whether the fouling of dreissenids (zebra and quagga (D. rostriformis bugensis) mussels) has a negative impact on native (Anodonta anatina, Unio pictorum and U. tumidus) and invasive (Corbicula fluminea and Sinanodonta woodiana) bivalves and whether there are any interspecific and temporal variations in fouling intensity and physiological condition measured by standard condition index and glycogen content. A significant negative impact was detected on native unionids only in July and September (no impact was detected in May), when the fouling rate was high. For invasive species, a significant negative impact was detected on S. woodiana with a high level of dressenid infestation; whereas no significant impact was detected on C. fluminea. Overall, this study confirms that Dreissena may threaten unionid species including the invasive S. woodiana, although high interspecific and temporal variations were observed. This situation should be taken into account in future ecological and conservational assessments because species respond differently to Dreissena fouling and effects seem to be more pronounced in late summer/early autumn. In addition, this study provides the first evidence that the invasive C. fluminea appear to be less vulnerable to dressenid fouling.The study was supported by the Hungarian Scientific Fund (KTIA-OTKA) under the contract No. CNK80140

2016 ACR-EULAR adult dermatomyositis and polymyositis and juvenile dermatomyositis response criteria-methodological aspects

Objective. The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM. Methods. Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data. Results. Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference. Conclusion. Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis

Trends in dermatomyositis- and polymyositis-related mortality in the state of São Paulo, Brazil, 1985-2007: multiple cause-of-death analysis

<p>Abstract</p> <p>Background</p> <p>Dermatomyositis (DM) and polymyositis (PM) are rare systemic autoimmune rheumatic diseases with high fatality rates. There have been few population-based mortality studies of dermatomyositis and polymyositis in the world, and none have been conducted in Brazil. The objective of the present study was to employ multiple-cause-of-death methodology in the analysis of trends in mortality related to dermatomyositis and polymyositis in the state of São Paulo, Brazil, between 1985 and 2007.</p> <p>Methods</p> <p>We analyzed mortality data from the São Paulo State Data Analysis System, selecting all death certificates on which DM or PM was listed as a cause of death. The variables sex, age and underlying, associated or total mentions of causes of death were studied using mortality rates, proportions and historical trends. Statistical analysis were performed by chi-square and H Kruskal-Wallis tests, variance analysis and linear regression. A p value less than 0.05 was regarded as significant.</p> <p>Results</p> <p>Over a 23-year period, there were 318 DM-related deaths and 316 PM-related deaths. Overall, DM/PM was designated as an underlying cause in 55.2% and as an associated cause in 44.8%; among 634 total deaths females accounted for 71.5%. During the study period, age- and gender-adjusted DM mortality rates did not change significantly, although PM as an underlying cause and total mentions of PM trended lower (p < 0.05). The mean ages at death were 47.76 ± 20.81 years for DM and 54.24 ± 17.94 years for PM (p = 0.0003). For DM/PM, respectively, as underlying causes, the principal associated causes of death were as follows: pneumonia (in 43.8%/33.5%); respiratory failure (in 34.4%/32.3%); interstitial pulmonary diseases and other pulmonary conditions (in 28.9%/17.6%); and septicemia (in 22.8%/15.9%). For DM/PM, respectively, as associated causes, the following were the principal underlying causes of death: respiratory disorders (in 28.3%/26.0%); circulatory disorders (in 17.4%/20.5%); neoplasms (in 16.7%/13.7%); infectious and parasitic diseases (in 11.6%/9.6%); and gastrointestinal disorders (in 8.0%/4.8%). Of the 318 DM-related deaths, 36 involved neoplasms, compared with 20 of the 316 PM-related deaths (p = 0.03).</p> <p>Conclusions</p> <p>Our study using multiple cause of deaths found that DM/PM were identified as the underlying cause of death in only 55.2% of the deaths, indicating that both diseases were underestimated in the primary mortality statistics. We observed a predominance of deaths in women and in older individuals, as well as a trend toward stability in the mortality rates. We have confirmed that the risk of death is greater when either disease is accompanied by neoplasm, albeit to lesser degree in individuals with PM. The investigation of the underlying and associated causes of death related to DM/PM broaden the knowledge of the natural history of both diseases and could help integrate mortality data for use in the evaluation of control measures for DM/PM.</p

Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis:the SHARE initiative

BACKGROUND: In 2012, a European initiative called Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is possibly its most devastating extra-articular manifestation. Evidence-based guidelines are sparse and management is mostly based on physicians' experience. Consequently, treatment practices differ widely, within and between nations. OBJECTIVES: To provide recommendations for the diagnosis and treatment of JIA-associated uveitis. METHODS: Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was constituted, consisting of nine experienced paediatric rheumatologists and three experts in ophthalmology from Europe. Recommendations derived from a validated systematic literature review were evaluated by an Expert Committee and subsequently discussed at two consensus meetings using nominal group techniques. Recommendations were accepted if >80% agreement was reached (including all three ophthalmologists). RESULTS: In total, 22 recommendations were accepted (with >80% agreement among experts): 3 on diagnosis, 5 on disease activity measurements, 12 on treatment and 2 on future recommendations. CONCLUSIONS: The SHARE initiative aims to identify best practices for treatment of patients suffering from JIA-associated uveitis. Within this remit, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated by an evidence-informed consensus process to suggest a standard of care for JIA-associated uveitis patients throughout Europe