Characterization of Hantavirus N Protein Intracellular Dynamics and Localization

Hantaviruses are enveloped viruses that possess a tri-segmented, negative-sense RNA genome. The viral S-segment encodes the multifunctional nucleocapsid protein (N), which is involved in genome packaging, intracellular protein transport, immunoregulation, and several other crucial processes during hantavirus infection. In this study, we generated fluorescently tagged N protein constructs derived from Puumalavirus (PUUV), the dominant hantavirus species in Central, Northern, and Eastern Europe. We comprehensively characterized this protein in the rodent cell line CHO-K1, monitoring the dynamics of N protein complex formation and investigating co-localization with host proteins as well as the viral glycoproteins Gc and Gn. We observed formation of large, fibrillar PUUV N protein aggregates, rapidly coalescing from early punctate and spike-like assemblies. Moreover, we found significant spatial correlation of N with vimentin, actin, and P-bodies but not with microtubules. N constructs also co-localized with Gn and Gc albeit not as strongly as the glycoproteins associated with each other. Finally, we assessed oligomerization of N constructs, observing efficient and concentration-dependent multimerization, with complexes comprising more than 10 individual proteins.     

Pseudogout--CPPD arthropathy, Case reports.

Pseudogout, or calcium pyrophosphate arthropathy, is a crystalline synovitis, characterised either by acute attacks of joint pain, which usually occur in the large joints, or by a more chronic, progressive form of joint disease. The essential features of the disease are chondrocalcinosis and the presence of pyrophosphate crystals in the synovial fluid. The exact pathogenesis is unknown. Case reports of 2 patients with confiemed pseudogout, and of 1 who is suspected to be suffering from the disease, as well as a summary of the outstanding aspects of the condition, are presented.     

P59(fyn) is upregulated in anergic CD8+ T cells

The ultimate goal in clinical transplantation is achievement of graft tolerance. Despite long-term immunosuppression, alloantigens on transplants elicit alloresponses that can initiate organ rejection. Acute rejection is mediated by CD8(+) cytotoxic T cells, whereas chronic rejection is a result of many factors including non-immunological events. The aim of this study was to examine the molecular requirements of T cell anergy, a cellular state that is an integral component of tolerance in vivo. In vitro, the tolerant state is usually best represented by T cell anergy, which is defined by loss of the ability of T cells to produce and secrete interleukin-2 upon restimulation. In the literature, molecular changes in anergic CD4(+) T cells have been studied in great detail, but only little is known about functional and biochemical characteristics of anergic CD8(+) T lymphocytes. In this study, we demonstrate, that CD8(+) T cells are rendered anergic by TCR stimulation without costimulation. They exhibit impaired interleukin-2 production and tyrosine-phosphorylation, but markedly upregulated p59(fyn) expression, which could be shown to be an early event during anergization. Anergic CD8(+) T lymphocytes show elevated surface expression of early activation markers as well as costimulatory molecules, especially that of CTLA4. These results, are an important component for the discovery of potential molecular targets, which contribute to the development and maintenance of tolerance.     

Zulässigkeit von Durchsuchungen in Arztpraxen

Ohne Zusammenfassung     

Über die Analgesieprüfung von Veronal-Pyramidongemischen im Tierversuch

Ohne ZusammenfassungMit 1 Textabbildung.     

Benefit-risk analysis of different risk-related surveillance schedules following colorectal polypectomy

BACKGROUND/AIMS: For colorectal screening patients a gain of life time was previously calculated to be about 30-50 days. Different recommendations for recognizing at-risk groups and defining surveillance intervals after an initial finding of colorectal adenomas have been published. However, no benefit-risk analysis regarding specific long-term effects of follow-up patients has been reported to date. METHODOLOGY: A Markov model based on time-dependent transition possibilities was developed to compare two surveillance schedules: recommendations based on the Erlangen Registry of Colorectal Polyps (ERCRP) and the National Polyp Study (NPS). The outcome was calculated for a 50-year-old patient with 30 years of follow-up after initial polypectomy. The data used in this model were taken from different sources, namely the ERCRP, the German Study Group of Colorectal Cancer, the German Statistical Yearbook, and from meta-analyses of studies reporting data on complications and sensitivity of colonoscopy. RESULTS: Patients under surveillance have a mean lifetime gain of 98 (ERCRP) and 91 (NPS) days compared with those who do not come for surveillance. Approximately 84% and 79% of deaths from colorectal carcinoma (CRC) could be prevented if patients were followed up according to the recommendations of the ERCRP and the NPS, respectively. The risk of death due to colonoscopy for patients during followup is about 0.05% lifetime risk. Sensitivity analysis showed the stability of the results under a wide range of reasonable variations of relevant parameters. In a pessimistic one-way sensitivity analysis regarding compliance, effectiveness was reduced to one third. CONCLUSIONS: Surveillance using colonoscopy is an effective tool for preventing CRC after colorectal polypectomy and similar to the screening procedure. The effectiveness is slightly higher when following the recommendations of the ERCRP, especially if a more realistic compliance is assumed.