Peripheral blood mononuclear cells represent a reservoir of bovine papillomavirus DNA in sarcoid-affected equines

Bovine papillomaviruses of types 1 and 2 (BPV-1 and -2) chiefly contribute to equine sarcoid pathogenesis. However, the mode of virus transmission and the presence of latent infections are largely unknown. This study established a PCR protocol allowing detection of

Serological evidence for the association of Bartonella henselae infection with arrhythmogenic right ventricular cardiomyopathy

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden death in young adults. On the basis of histopathological findings its pathogenesis may involve both a genetic origin and an inflammatory process. Bartonella henselae may cause endomyocarditis and was detected in myocardium from a young male who succumbed to sudden cardiac death. HYPOTHESIS: We hypothesized that chronic infection with Bartonella henselae could contribute to the pathogenesis of ARVC. METHODS: We investigated sera from 49 patients with ARVC for IgG antibodies to Bartonella henselae. In this study, 58 Swiss blood donors tested by the same method served as controls. RESULTS: Six patients with ARVC (12%) had positive (>1:256) IgG titres in the immunofluorescence test with Bartonella henselae. In contrast, only 1 elevated titre was found in 58 controls (p < or = 0.05). Interestingly, all patients with increased titres had no familial occurrence of ARVC. CONCLUSIONS: Further studies in larger patient cohorts seem justified to investigate a possible causal link between chronic Bartonella henselae and ARVC, in particular its sporadic (nonfamilial) form.

Stratification of cumulative antibiograms in hospitals for hospital unit, specimen type, isolate sequence and duration of hospital stay

BACKGROUND: Empirical antibiotic therapy is based on patients' characteristics and antimicrobial susceptibility data. Hospital-wide cumulative antibiograms may not sufficiently support informed decision-making for optimal treatment of hospitalized patients. METHODS: We studied different approaches to analysing antimicrobial susceptibility rates (SRs) of all diagnostic bacterial isolates collected from patients hospitalized between July 2005 and June 2007 at the University Hospital in Zurich, Switzerland. We compared stratification for unit-specific, specimen type-specific (blood, urinary, respiratory versus all specimens) and isolate sequence-specific (first, follow-up versus all isolates) data with hospital-wide cumulative antibiograms, and studied changes of mean SR during the course of hospitalization. RESULTS: A total of 16 281 isolates (7965 first, 1201 follow-up and 7115 repeat isolates) were tested. We found relevant differences in SRs across different hospital departments. Mean SRs of Escherichia coli to ciprofloxacin ranged between 64.5% and 95.1% in various departments, and mean SRs of Pseudomonas aeruginosa to imipenem and meropenem ranged from 54.2% to 100% and 80.4% to 100%, respectively. Compared with hospital cumulative antibiograms, lower SRs were observed in intensive care unit specimens, follow-up isolates and isolates causing nosocomial infections (except for Staphylococcus aureus). Decreasing SRs were observed in first isolates of coagulase-negative staphylococci with increasing interval between hospital admission and specimen collection. Isolates from different anatomical sites showed variations in SRs. CONCLUSIONS: We recommend the reporting of unit-specific rather than hospital-wide cumulative antibiograms. Decreasing antimicrobial susceptibility during hospitalization and variations in SRs in isolates from different anatomical sites should be taken into account when selecting empirical antibiotic treatment.

Performance of Interleukin-6 and Interleukin-8 serum levels in pediatric oncology patients with neutropenia and fever for the assessment of low-risk

BACKGROUND: Patients with chemotherapy-related neutropenia and fever are usually hospitalized and treated on empirical intravenous broad-spectrum antibiotic regimens. Early diagnosis of sepsis in children with febrile neutropenia remains difficult due to non-specific clinical and laboratory signs of infection. We aimed to analyze whether IL-6 and IL-8 could define a group of patients at low risk of septicemia. METHODS: A prospective study was performed to assess the potential value of IL-6, IL-8 and C-reactive protein serum levels to predict severe bacterial infection or bacteremia in febrile neutropenic children with cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test, Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating Characteristics. RESULTS: The analysis of cytokine levels measured at the onset of fever indicated that IL-6 and IL-8 are useful to define a possible group of patients with low risk of sepsis. In predicting bacteremia or severe bacterial infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42 pg/ml showing a high sensitivity (90%) and specificity (85%). CONCLUSION: These findings may have clinical implications for risk-based antimicrobial treatment strategies.

Monomerization of dimeric IgG of intravenous immunoglobulin (IVIg) increases the antibody reactivity against intracellular antigens

Intravenous immunoglobulin (IVIg) preparations are derived from pooled plasma from up to 60,000 healthy human donors and reflect the immunologic experience of the donor population. IVIg contains monomeric and dimeric IgG populations which are in a dynamic equilibrium depending on concentration, pH, temperature, donor pool size, time and stabilizers added in order to keep the portion of dimeric IgG below a certain level. In the present study, monomeric and dimeric fractions were isolated by size exclusion chromatography. The dimeric fractions, however, showed a dynamic instability and tended to dissociate. Both dimeric and monomeric IgG fractions were acid treated (pH 4) in order to dissociate the dimeric IgG. Western-blot analysis identified a sub-population of SDS resistant IgG dimers. Furthermore, the reactivities of the fractions were tested against a panel of self- and exo-antigens. There was a marked increase in activity of the dimeric compared to the monomeric IgG fraction against various intracellular self-antigens. Our data indicates that the increased reactivities of pH 4-treated fractions can mainly be attributed to dimer dissociation, as pH 4-treated monomers do not show significantly increased activities against a range of antigens.

Quo vadis Wirtschaftsinformatik - Festschrift für Prof. Gerhard F. Knolmayer zum 60. Geburtstag

Renommierte Wissenschaftler und Praktiker nehmen aus verschiedenen Perspektiven Stellung zu Bedeutung, Positionierung und zukünftiger Ausrichtung der Wirtschaftsinformatik.

Loss of alpha10beta1 integrin expression leads to moderate dysfunction of growth plate chondrocytes

Integrin alpha10beta1 is a collagen-binding integrin expressed on chondrocytes. In order to unravel the role of the alpha10 integrin during development, we generated mice carrying a constitutive deletion of the alpha10 integrin gene. The mutant mice had a normal lifespan and were fertile but developed a growth retardation of the long bones. Analysis of the skeleton revealed defects in the growth plate after birth characterized by a disturbed columnar arrangement of chondrocytes, abnormal chondrocyte shape and reduced chondrocyte proliferation. Electron microscopy of growth plates from newborn mice revealed an increased number of apoptotic chondrocytes and reduced density of the collagen fibrillar network compared to these structures in control mice. These results demonstrate that integrin alpha10beta1 plays a specific role in growth plate morphogenesis and function.

Tenomodulin is necessary for tenocyte proliferation and tendon maturation

Tenomodulin (Tnmd) is a member of a new family of type II transmembrane glycoproteins. It is predominantly expressed in tendons, ligaments, and eyes, whereas the only other family member, chondromodulin I (ChM-I), is highly expressed in cartilage and at lower levels in the eye and thymus. The C-terminal extracellular domains of both proteins were shown to modulate endothelial-cell proliferation and tube formation in vitro and in vivo. We analyzed Tnmd function in vivo and provide evidence that Tnmd is processed in vivo and that the proteolytically cleaved C-terminal domain can be found in tendon extracts. Loss of Tnmd expression in gene targeted mice abated tenocyte proliferation and led to a reduced tenocyte density. The deposited amounts of extracellular matrix proteins, including collagen types I, II, III, and VI and decorin, lumican, aggrecan, and matrilin-2, were not affected, but the calibers of collagen fibrils varied significantly and exhibited increased maximal diameters. Tnmd-deficient mice did not have changes in tendon vessel density, and mice lacking both Tnmd and ChM-I had normal retinal vascularization and neovascularization after oxygen-induced retinopathy. These results suggest that Tnmd is a regulator of tenocyte proliferation and is involved in collagen fibril maturation but do not confirm an in vivo involvement of Tnmd in angiogenesis.

Beta1 integrins differentially control extravasation of inflammatory cell subsets into the CNS during autoimmunity

Inhibiting the alpha(4) subunit of the integrin heterodimers alpha(4)beta(1) and alpha(4)beta(7) with the monoclonal antibody natalizumab is an effective treatment for multiple sclerosis (MS). However, the pharmacological action of natalizumab is not understood conclusively. Previous studies suggested that natalizumab inhibits activation, proliferation, or extravasation of inflammatory cells. To specify which mechanisms, cell types, and alpha(4) heterodimers are affected by the antibody treatment, we studied MS-like experimental autoimmune encephalomyelitis (EAE) in mice lacking the beta(1)-integrin gene either in all hematopoietic cells or selectively in T lymphocytes. Our results show that T cells critically rely on beta(1) integrins to accumulate in the central nervous system (CNS) during EAE, whereas CNS infiltration of beta(1)-deficient myeloid cells remains unaffected, suggesting that T cells are the main target of anti-alpha(4)-antibody blockade. We demonstrate that beta(1)-integrin expression on encephalitogenic T cells is critical for EAE development, and we therefore exclude alpha(4)beta(7) as a target integrin of the antibody treatment. T cells lacking beta(1) integrin are unable to firmly adhere to CNS endothelium in vivo, whereas their priming and expansion remain unaffected. Collectively, these results suggest that the primary action of natalizumab is interference with T cell extravasation via inhibition of alpha(4)beta(1) integrins.