Modulation of Suppressor Mechanisms in Allergic Contact Dermatitis: 5. Evidence That Inhibition of Suppressor T Lymphocytes by Corynebacterium parvum Is Mediated by Interferon

Using a contact hypersensitivity model in BALB/c mice we have previously been able to show that Corynehacterium parvum or C. parvum serum (C.p.s.) of mice treated 24hr before with C. parvum inhibited the suppressor T-lyrnphocyte (TScell) response induced by epicutaneous antigen overload with 2,4-dinitrofluorobenzene (DNFB) or by i.v. injection of 2,4-dinitrobenzene sulfonic acid (DNBSO3) without inhibition of the T effector cell response (TDH-cell). In the present investigation we further analyzed the factor responsible for TS-cell inhibition. Treatment of the C.p.s. with sheep-antimouse interferon (IFN) globulin neutralized its TS-cell inhibitory effect. Intravenous (i.v.) injection of a crude mouse fibroblast IFN (340 U per mouse) 2hr after i.v. application of a dose of DNBSO3 inducing tolerance had a similar TS-cell inhibitory effect as observed with C.p.s. Injection of an electrophoretically pure α- and β-IFN preparation (1000 U per mouse) increased contact sensitivity in mice sensitized with an antigen overload and inhibited the induction of TS-cells by DNBSO3 i.v. This result is highly suggestive that the TS-cell inhibitory factor in serum of C. parum-treated mice is IFN and it shows that TS-cells as compared to TDH-cells are susceptible to the inhibitory effect of highly purified IFN. This finding suggests that IFN may be an important immunoregulatory factor of delayed hypersensitivity not only in contact allergy but also in bacterial and viral defense

4,7-Diaza-1-azoniacyclo­nonane bromide

The title compound, C6H16N3 +·Br−, is the bromide of the monoprotonated aza­macrocyclic triamine 1,4,7-triaza­cyclo­nonane (tacn). The threefold axis of the triamine is broken by the protonation of one of the three amine functions. The ammonium proton is bonded in an intra­molecular symmetrically bifurcated hydrogen bond to the two endodentate amine functions. Direct cation–anion contacts are established via N—H⋯Br hydrogen bonds between the bromide anions and tacnH+ cations

Staatliche Anerkennung auf Abwegen. Über die Bedeutung der Erziehungswissenschaft und deren Marginalisierung in Studiengängen der Sozialen Arbeit

Die Bedeutung der Erziehungswissenschaft für die Sozialpädagogik und der Sozialen Arbeit wird herausgearbeitet. Hierbei verweisen die Autor*innen auf die zentrale und grundlegende Bedeutung der Erziehungswissenschaft etwa für die Arbeit mit Kindern und Jugendlichen und verorten damit die Sozialpädagogik als eigentliche Kerndisziplin einer Sozialen Arbeit. (DIPF/Orig.

The conception of network- and evidence-based school development. A report of the project "Developing potentials - empowering schools"

Netzwerk- und evidenzbasierte Schulentwicklungsansätze stellen geeignete Strategien zur Förderung der Qualität von Schulen in schwierigen Lagen dar. Das Projekt "Potenziale entwickeln - Schulen stärken" hat diese Unterstützungselemente in einem innovativen Ansatz konzeptionell vereint. Neben der Beschreibung dieser Konzeption wird in dem Beitrag auf die Vorgehensweise zur Rekontextualisierung von empirischem Material in der Schulpraxis eingegangen, das im Projekt zum Einsatz kommt. (DIPF/Orig.)Approaches of network- and evidence-based school development are appropriate strategies to improve the quality of schools in challenging circumstances. The project "Developing Potentials - Empowering Schools" connects these concepts innovatively. The article describes the conception as well as its strategy, which is used for recontextualization of empirical material in schools\u27 practice. (DIPF/Orig.

Mixed large cell neuroendocrine carcinoma and squamous cell carcinoma of the colon: detailed molecular characterisation of two cases indicates a distinct colorectal cancer entity

We present two rare cases of mixed large cell neuroendocrine carcinoma and squamous cell carcinoma of the colon. A literature search revealed only three published cases with similar histology but none of these reports provided profound molecular and mutational analyses. Our two cases exhibited a distinct, colon-like immunophenotype with strong nuclear CDX2 and beta-catenin expression in more than 90% of the tumour cells of both components. We analysed the two carcinomas regarding microsatellite stability, RAS, BRAF and PD-L1 status. In addition, next-generation panel sequencing with Ion AmpliSe (TM) psi Cancer Hotspot Panel v2 was performed. This approach revealed mutations in FBXW7, CTNNB1 and PIK3CA in the first case and FBXW7 and RB1 mutations in the second case. We looked for similar mutational patterns in three publicly available colorectal adenocarcinoma data sets, as well as in collections of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) and colorectal neuroendocrine carcinomas. This approach indicated that the FBXW7 point mutation, without being accompanied by classical adenoma-carcinoma sequence mutations, such as APC, KRAS and TP53, likely occurs at a relatively high frequency in mixed neuroendocrine and squamous cell carcinoma and therefore may be characteristic for this rare tumour type. FBXW7 codifies the substrate recognition element of an ubiquitin ligase, and inactivating FBXW7 mutations lead to an exceptional accumulation of its target beta-catenin which results in overactivation of the Wnt-signalling pathway. In line with previously described hypotheses of de-differentiation of colon cells by enhanced Wnt-signalling, our data indicate a crucial role for mutant FBXW7 in the unusual morphological switch that determines these rare neoplasms. Therefore, mixed large cell neuroendocrine and a squamous cell carcinoma can be considered as a distinct carcinoma entity in the colon, defined by morphology, immunophenotype and distinct molecular genetic alteration(s)

Student Evaluation Scale for Medical Courses with Simulations of the Doctor-Patient Interaction (SES-Sim)

Objective: Simulations of doctor-patient interactions have become a popular method for the training of medical skills, primarily communication skills. A new questionnaire for the measurement of students’ satisfaction with medical courses using this technique is presented, the Student Evaluation Scale for Medical Courses with Simulations of the Doctor-Patient Interaction (SES-Sim)

Economic Impact of Porcine Reproductive and Respiratory Syndrome Virus on U.S. Pork Producers

Information is provided on the productivity and economic impacts of PRRS disease in the U.S. breeding herd and growing pig herd. The total annual loss from PRRS in U.S. breeding herds was estimated at $302.06 million, i.e.,$52.19 per breeding female or $2.36 per pig weaned. The majority of the loss in the breeding herd was due to reduced revenue ($300.4 million) resulting from weaning 8.3 million fewer pigs. Combining the losses in the breeding and growing pig herds resulted in 9.9 million fewer pigs, or 2.41 billion fewer pounds of pork (carcass weight), sold per year in the U.S. The estimated annual loss in the growing pig herd was $361.8 million or$62.52 per breeding female. As in the breeding herd, lost revenue of $1.62 billion, rather than increased cost, was the primary source of losses attributed to PRRS. With PRRS, costs were lowered by$1.25 billion because fewer pigs and pounds of pork were produced, thereby partially offsetting the lost revenue. In summary, the estimated total cost of PRRS in the U.S. national breeding and growing pig herd was at $664 million annually ($1.8 million per day). In addition, information on veterinary costs, biosecurity costs, and other costs from the survey of expert opinion were used to estimate these annual costs attributed to PRRS virus. The additional veterinary costs were estimated to be $140.11 million annually. The annual biosecurity and other outbreak related costs attributed to PRRS were estimated to be$191.86 million and $145.82 million, respectively. The total additional costs attributed to PRRS for veterinary, biosecurity and other outbreak related costs were$477.79 million annually

Economic Analysis of PRRS Virus Elimination from a Herd

A net present value (NPV) analysis was performed to evaluate PRRS virus elimination from individual herds. The NPV analysis conducted for this study is the first analysis of which the authors are aware that accounts for the more severe negative production and economic consequences of a PRRS outbreak when a PRRS virus-free herd becomes reinfected. Two approaches to eliminating PRRS virus from a herd were evaluated: (1) complete depopulation and repopulation (CDR) of the herd with PRRS virus-free breeding animals and (2) herd closure and rollover (HCR). When HCR was the method of elimination, the time herds needed to remain PRRS virus-free to break even on the cost of elimination ranged from 4 months to 26 months. When CDR was the method of elimination, the time herds needed to remain PRRS virus-free to break even ranged from 18 to 83 months

Assessment of the economic impact of porcine reproductive and respiratory syndrome virus on United States pork producers

Objective: To estimate the current annual economic impact of porcine reproductive and respiratory syndrome virus (PRRSV) on the US swine industry

Sialylation acts as a checkpoint for innate immune responses in the central nervous system.

Sialic acids are monosaccharides that normally terminate the glycan chains of cell surface glyco-proteins and -lipids in mammals, and are highly enriched in the central nervous tissue. Sialic acids are conjugated to proteins and lipids (termed "sialylation") by specific sialyltransferases, and are removed ("desialylation") by neuraminidases. Cell surface sialic acids are sensed by complement factor H (FH) to inhibit complement activation or by sialic acid-binding immunoglobulin-like lectin (SIGLEC) receptors to inhibit microglial activation, phagocytosis, and oxidative burst. In contrast, desialylation of cells enables binding of the opsonins C1, calreticulin, galectin-3, and collectins, stimulating phagocytosis of such cells. Hypersialylation is used by bacteria and cancers as camouflage to escape immune recognition, while polysialylation of neurons protects synapses and neurogenesis. Insufficient lysosomal cleavage of sialylated molecules can lead to lysosomal accumulation of lipids and aggregated proteins, which if excessive may be expelled into the extracellular space. On the other hand, desialylation of immune receptors can activate them or trigger removal of proteins. Loss of inhibitory SIGLECs or FH triggers reduced clearance of aggregates, oxidative brain damage and complement-mediated retinal damage. Thus, cell surface sialylation recognized by FH, SIGLEC, and other immune-related receptors acts as a major checkpoint inhibitor of innate immune responses in the central nervous system, while excessive cleavage of sialic acid residues and consequently removing this checkpoint inhibitor may trigger lipid accumulation, protein aggregation, inflammation, and neurodegeneration