[Rosai-Dorfman disease as a rare cause of a pancreatic mass]. / Die Rosai-Dorfman-Erkrankung als seltene Ursache für einen Pankreastumor.

The CT and MRI scans of a 70-year-old male patient revealed a mass in the pancreatic head and a 2.8-cm peripancreatic lymph node. Under steroid therapy the mass did not show regression. Finally, a pancreatoduodenectomy was performed. Histologically, Rosai-Dorfman disease (RDD) was diagnosed. RDD is a rare histiocytic disorder with usually nodal but sometimes also extranodal involvement. Herein we report a rare case of extranodal RDD with intrapancreatic localization.

Purulent myositis of the thigh as a presentation of perforated low rectal cancer.

Purulent myositis is an acute, intramuscular bacterial infection involving abscess formation most commonly affecting the quadriceps, hamstring and gluteal muscles. We present a case of extensive purulent myositis of the thigh and lower leg caused by bowel perforation below the peritoneal reflection secondary to rectal cancer. Cases of lower limb and perineal purulent myositis should raise suspicion of rectal perforation and should prompt investigations to exclude rectal malignancy.

Effect of probiotic on innate inflammatory response and viral shedding in experimental rhinovirus infection - a randomised controlled trial.

Ingestion of probiotics appears to have modest effects on the incidence of viral respiratory infection. The mechanism of these effects is not clear; however, there is evidence from animal models that the probiotic may have an effect on innate immune responses to pathogens. The purpose of this randomised, placebo-controlled study was to determine the effect of administration of Bifidobacterium animalis subspecies lactis Bl-04 on innate and adaptive host responses to experimental rhinovirus challenge. The effect on the response of chemokine (C-X-C motif) ligand 8 (CXCL8) to rhinovirus infection was defined as the primary endpoint for the study. 152 seronegative volunteers who had been supplemented for 28 days, 73 with probiotic and 79 with placebo, were challenged with RV-A39. Supplement or placebo administration was then continued for five days during collection of specimens for assessment of host response, infection, and symptoms. 58 probiotic and 57 placebo-supplemented volunteers met protocol-defined criteria for analysis. Probiotic resulted in higher nasal lavage CXCL8 on day 0 prior to virus challenge (90 vs 58 pg/ml, respectively, P=0.04, ANCOVA). The CXCL8 response to rhinovirus infection in nasal lavage was significantly reduced in the probiotic treated group (P=0.03, ANCOVA). Probiotic was also associated with a reduction in nasal lavage virus titre and the proportion of subjects shedding virus in nasal secretions (76% in the probiotic group, 91% in the placebo group, P=0.04, Fisher Exact test). The administration of probiotic did not influence lower respiratory inflammation (assessed by exhaled nitric oxide), subjective symptom scores, or infection rate. This study demonstrates that ingestion of Bl-04 may have an effect on the baseline state of innate immunity in the nose and on the subsequent response of the human host to rhinovirus infection. Clinicaltrials.gov registry number: NCT01669603.

Functional analysis of -351 interleukin-9 promoter polymorphism reveals an activator controlled by NF-kappaB.

Genetic studies have shown linkages for asthma to the chromosomal region 5q31-q33 in humans that includes the IL-9 gene. An A-to-G base substitution has been identified at bp -351 in the IL-9 promoter. The role of this polymorphism in IL-9 promoter function was assessed utilizing CD4+ T cells purified from individuals with one or two of the G alleles in comparison to those homozygous for the wild-type A. The presence of an A at -351 (A allele) increased mitogen-stimulated IL-9 transcription twofold in comparison to subjects with one or two G alleles at this position. Binding of nuclear extract proteins from IL-9-producing human cell lines to DNA sequences including this base exchange demonstrated specific binding of the transcription factor NF-kappaB. Binding of NF-kappaB to the IL-9 promoter was confirmed in vivo using the chromatin immunoprecipitation assay. Recombinant NF-kappaB bound to a promoter fragment with the A allele with fivefold higher affinity than it did to a promoter with the G allele. Individuals carrying the A allele of the IL-9 promoter display increased synthesis of IL-9, which may result in strong Th2 immune responses and a modulation of their susceptibility to infectious, neoplastic, parasitic or atopic disease.

Dissimilar immunogenicities of human papillomavirus E7 and adenovirus E1A proteins influence primary tumor development.

Although human papillomaviruses (HPV) and adenoviruses (Ad) both transform cells by expressing functionally related oncogenes (Ad-E1A/E1B; HPV-E7/E6), only HPV are oncogenic in humans. Prior studies have shown that HPV-transformed cells are resistant to NK cell lysis and E7- and E6-specific CTL are inefficiently generated in women with HPV-induced cervical cancer. Therefore, we postulated that the dissimilar oncogenicities of Ad and HPV may be caused by a protective NK and T cell response that is triggered by transformed cells expressing E1A, but not by E7. To test this hypothesis, mice that were either immunologically intact, lacked T cells, or lacked both NK and T cells were challenged with Ad serotype 5 (Ad5)-E1A- or HPV16-E7-transfected tumor cells. E7-expressing tumor cells were resistant to NK cell lysis in vitro and failed to elicit a measurable anti-tumor NK or T cell response in vivo. The concomitant expression of E6 did not change this phenotype. In contrast, E1A-expressing tumor cells were sensitive to NK lysis in vitro and triggered a protective NK and T cell immune response in vivo. These data suggest differences in the capacities of E1A or E7 oncoproteins to trigger protective anti-tumor immune responses may contribute to the dissimilar oncogenicities of Ad and HPV in humans.

Discrete promoter elements affect specific properties of RNA polymerase II transcription complexes.

The frequency of transcription initiation at specific RNA polymerase II promoters is, in many cases, related to the ability of the promoter to recruit the transcription machinery to a specific site. However, there may also be functional differences in the properties of assembled transcription complexes that are promoter-specific or regulator-dependent and affect their activity. Transcription complexes formed on variants of the adenovirus major late (AdML) promoter were found to differ in several ways. Mutations in the initiator element increased the sarkosyl sensitivity of the rate of elongation and decreased the rate of early steps in initiation as revealed by a sarkosyl challenge assay that exploited the resistance of RNA synthesis to high concentrations of sarkosyl after formation of one or two phospho-diester bonds. Similar, but clearly distinct, effects were also observed after deletion of the binding site for upstream stimulatory factor from the AdML promoter. In contrast, deletion of binding sites for nuclear factor 1 and Oct-1, as well as mutations in the recognition sequence for initiation site binding protein, were without apparent effect on transcription complexes on templates containing the mouse mammary tumor virus promoter.

RNA polymerase II transcription complex assembly in nuclear extracts.

In vitro transcription systems based on nuclear extracts of eukaryotic cells continue to be valuable experimental systems for assessing function of promoter sequences and defining new activities involved in transcription complex assembly and activity, but many aspects of such systems have not been experimentally examined. Here, transcription complex assembly on the promoter from the long terminal repeat of mouse mammary tumor virus was assessed in vitro with a transcription system derived from nuclear extracts of cultured HeLa cells. The extent of preinitiation complex assembly on the promoter was limited by the availability of template, even though only a small fraction of the template present in the assays participated in transcription. These results support a model for transcription complex assembly in which template DNA has two alternative fates, one leading to assembly of a functional transcription complex, and another that leads to irreversible template inactivation. The observed kinetics of assembly reflects loss of template by both pathways and is dominated by a relatively rapid rate of template inactivation. Supplementing nuclear extracts with purified TATA binding protein increased the extent as well as the apparent rate of assembly. Both effects can be explained by a TATA binding protein-dependent increase in the rate of assembly that leads to altered partitioning of template between competing pathways.

Effect of oximetry error on the diagnostic value of the Qp/Qs ratio.

As a quantitative assessment of the magnitude of shunting, the ratio of pulmonary to systemic blood flow (Qp/Qs) plays an important role not only in the oximetric diagnosis of intracardiac and great-vessel shunts but also in the treatment of the patient. However, the oxygen saturation measurements used to compute the Qp/Qs ratio contain errors due to physiological variability and measurement error of the oximeter used to analyze the blood samples. We have developed a mathematical model to describe the variability that oximetry errors contribute to the uncertainty in the Qp/Qs ratio. Using this model, we compute the probability of making an inappropriate recommendation regarding corrective surgery when a particular value of the ratio is the criterion for surgery, e.g. a Qp/Qs ratio >2. This report also contains a spreadsheet that readers can use to analyze their own oximetry data by computing confidence intervals for the Qp/Qs ratio. The results presented here support the following conclusions. First, because the Qp/Qs ratio is calculated from saturation measurements at four different sites, oximetry errors make the Qp/Qs ratio less effective at detecting the presence of a shunt than the conventional step-up method that depends on samples from only two sites. Second, although oximetry errors are equally likely to cause the calculated Qp/Qs ratio to overestimate the true Qp/Qs ratio as to underestimate it, the overestimations on average have greater magnitudes than the underestimations. Third, in comparison with an oximeter that has 2.5% measurement error, using an oximeter with 1% or less error greatly reduces the uncertainty in the Qp/Qs ratio and thus increases the probability of reaching the right decision regarding corrective surgery. Fourth, the variability in apparent Qp/Qs ratios is also greatly diminished by taking multiple blood samples from each of the four requisite sites and averaging them before calculating the Qp/Qs ratio. Although increasing the number of blood samples from each site can compensate for the error of an oximeter, this approach can be impractical, particularly if the oximeter error is 2.5% or greater.