Fusion with mouse thymocytes leads to expression of p30 antigen in fibroblasts of BALB/Mo mice

Embryonic fibroblasts of BALB/Mo mice carrying the endogenous genome of Moloney murine leukemia virus (M-MuLV) in addition to murine type C viruses were fused with Swiss mouse thymocytes, B lymphocytes, macrophages, or embryonic fibroblasts. We wanted to determine whether these cells contained physiological factors involved in induction of the integrated viral genome(s). Fusion with thymocytes and, to a lesser extent, fusion with B lymphocytes induced viral genome expression as demonstrated by the appearance of viral structural protein p30 detected by immunofluorescence. Maximal expression of p30 was observed about 36 hr after the fusion event, using thymocytes from 1- to 2-week-old Swiss mice. This temporary expression of p30 was not accompanied by release of infectious virus. Fusion of BALB/Mo fibroblasts with Swiss mouse macrophages or embryonic fibroblasts led to neither the production of p30 nor the release of detectable infectious virus. These results suggest the existence of thymocyte-specific and possibly B lymphocyte-specific factor(s) involved in the control of expression of integrated viral genome(s).     

Congenital clubfoot in Europe: A population‐based study

We aimed to assess prevalence, birth outcome, associated anomalies and prenatal diagnosis of congenital clubfoot in Europe using data from the EUROCAT network, and to validate the recording of congenital clubfoot as a major congenital anomaly by EUROCAT registries. Cases of congenital clubfoot were included from 18 EUROCAT registries covering more than 4.8 million births in 1995–2011. Cases without chromosomal anomalies born during 2005–2009, were randomly selected for validation using a questionnaire on diagnostic details and treatment. There was 5,458 congenital clubfoot cases of which 5,056 (93%) were liveborn infants. Total prevalence of congenital clubfoot was 1.13 per 1,000 births (95% CI 1.10–1.16). Prevalence of congenital clubfoot without chromosomal anomaly was 1.08 per 1,000 births (95% CI 1.05–1.11) and prevalence of isolated congenital clubfoot was 0.92 per 1,000 births (95% CI 0.90–0.95), both with decreasing trends over time and large variations in prevalence by registry. The majority of cases were isolated congenital clubfoot (82%) and 11% had associated major congenital anomalies. Prenatal detection rate of isolated congenital clubfoot was 22% and increased over time. Among 301 validated congenital clubfoot cases, diagnosis was confirmed for 286 (95%). In conclusion, this large population‐based study found a decreasing trend of congenital clubfoot in Europe after 1999–2002, an increasing prenatal detection rate, and a high standard of coding of congenital clubfoot in EUROCAT.     

Interepithelial cells of the oral mucosa in mice

Summary Non-epithelial mesenchymal and neuroectodermal cells occur between the keratinocytes in the stratified squamous epithelium of the oral mucosa. These cells cannot be classified adequately by light microscopy. In the present study the oral mucosa of the lip, cheek and tongue of 50 mice were studied by light and electron microscopy. 3,025 mononuclear interepithelial cells were documented and analysed.Monocytogenic macrophages, plasma cells and mast cells were not found interepithelially and cannot be regarded as a regular constituent of the epithelium. Only a few neuroectodermal cells — in mice these are exclusively Merkel cells, with no melanocytes — were localized in the epithelium. The majority of the interepithelial cell population is made up of lymphocytes (22.8%) and Langerhans cells (56.8%). They are an integral constituent of the epithelium. Lymphocytes with rounded and indented nuclei can be identified. The larger and dendritic Langerhans cells are a specific cell of squamous epithelium and also occur in the oral mucosa. Not all cells which feature the cytological characteristics of Langerhans cells contain Langerhans or Birbeck granules. Accordingly these granules cannot be considered an exclusive identification characteristic. Two types of Langerhans cells can be differentiated. 80.9% have the more or less typical appearance known from the epidermis and were termed macrophagocytoid Langerhans cells. The nuclei are irregularly indented and moderately heterochromatic. 19.1% possessed conspicuous large, spherical, euchromatic nuclei and an electron-lucent cytoplasm. These were termed reticuloid Langerhans cells. About 20% of the interepithelial cell population could not be identified, neither as typical lymphocytes nor as Langerhans cells. These were small to medium sized cells with deeply indented cerebriform strongly heterochromatic nuclei. They are similar to the Sézary cells or mycosis fungoides cells of epidermotropic human T-cell lymphomas. The lymphocytic nature of these cells has been confirmed. It seems likely that differentiation of lymphocytes to cerebriform cells occurs within the epithelium. It is further discussed whether cerebriform cells are precursors of Langerhans cells, a conclusion suggested morphologically by transitional forms. This would imply that Langerhans cells originate from lymphocytes, and that the cerebriform cell is an intermediate step of differentiation. The microenvironment of the squamous epithelium may play a role in the process of differentiation, which could explain the epitheliotropy of lymphocytes. The possibility is considered that Langerhans cells and interdigitating reticulum cells of the T-cell area of lymph nodes are identical. The close functional cooperation of Langerhans cells, lymphocytes, and interdigitating reticulum cells in immunological defenses against external antigens is discussed.The authors wish to express their sincere appreciation to Miss P. Starck and Miss I. Brandt for invaluable technical assistance in this project.     

Randomized controlled trial comparing magnetic marker localization (MaMaLoc) with wire-guided localization in the treatment of early-stage breast cancer

Wire-guided localization (WGL) is the standard of care in the surgical treatment of nonpalpable breast tumors. In this study, we compare the use of a new magnetic marker localization (MaMaLoc) technique to WGL in the treatment of early-stage breast cancer patients. Open-label, single-center, randomized controlled trial comparing MaMaLoc (intervention) to WGL (control) in women with early-stage breast cancer. Primary outcome was surgical usability measured using the System Usability Scale (SUS, 0–100 score). Secondary outcomes were patient reported, clinical, and pathological outcomes such as retrieval rate, operative time, resected specimen weight, margin status, and reoperation rate. Thirty-two patients were analyzed in the MaMaLoc group and 35 in the WGL group. Patient and tumor characteristics were comparable between groups. No in situ complications occurred. Retrieval rate was 100% in both groups. Surgical usability was higher for MaMaLoc: 70.2 ± 8.9 vs. 58.1 ± 9.1, p < 0.001. Patients reported higher overall satisfaction with MaMaLoc (median score 5/5) versus WGL (score 4/5), p < 0.001. The use of magnetic marker localization (MaMaLoc) for early-stage breast cancer is effective and has higher surgical usability than standard WGL.     

Studying psychoactive substance use in injured patients: Does exclusion of late arriving patients bias the results?

BackgroundMost studies of the prevalence of psychoactive substances in injured emergency department patients have excluded those who arrive more than 6 h after injury. This may cause a selection bias. The aim of this study was: (1) to describe the characteristics of patients who arrive more than 6 h after injury, compared to patients who arrive sooner (2) to examine whether self-report can add to the assessment of alcohol use when the patient is assessed more than 6 h after injury.MethodsBlood sample analysis and self-report data were used to assess the prevalence of psychoactive substances in injured patients admitted to an emergency department within 48 h of injury (n = 1611). Discriminant function analysis was used to assess group differences.ResultsThe patients who arrived more than 6 h after injury differed significantly from those who arrived earlier in several respects. They more often screened positive for hypnotics; they were older, they were more likely to have had a fall and they were more often injured at home and at night. Self reported use of alcohol showed good consistency with blood sample screening within 6 h of injury and could therefore be used to assess alcohol use more than 6 h after injury.ConclusionsPatients who arrive more than 6 h after injury differ significantly from those who arrive earlier. Future studies on the prevalence of psychoactive substances in emergency departments could expand the inclusion window.     

Acute exercise-induced glycocalyx shedding does not differ between exercise modalities,but is associated with total antioxidative capacity

ObjectivesRegular physical exercise is known to protect endothelial integrity. It has been proposed that acute exercise-induced changes of the (anti-)oxidative system influence early (glycocalyx shedding) and sustained endothelial activation (shedding of endothelial cells, ECs) as well as endothelial-cell repair by circulating hematopoietic stem and progenitor cells (HPCs). However, results are not conclusive and data in trained participants performing different exercise modalities is lacking.DesignEighteen healthy, well-trained participants (9 runners, 9 cyclists; age: 29.7 ± 4.2 yrs) performed a strenuous acute exercise session consisting of 4 bouts of 4-min high-intensity with decreasing power profile and 3-min low-intensity in-between.MethodsAverage power/speed of intense phases was 85% of the peak achieved in a previous incremental test. Before and shortly after exercise, total oxidative and antioxidative capacities (TAC), shedding of syndecan-1, heparan sulfate, hyaluronan, ECs, and circulating HPCs were investigated.ResultsTAC decreased from 1.81 ± 0.42 nmol/L to 1.47 ± 0.23 nmol/L post-exercise (p = 0.010) only in runners. Exercise-induced early and sustained endothelial activation were enhanced post-exercise- syndecan-1: 103.2 ± 63.3 ng/mL to 111.3 ± 71.3 ng/mL, heparan sulfate: from 2637.9 ± 800.1 ng/mL to 3197.1 ± 1416.3 ng/mL, both p < 0.05; hyaluronan: 84.3 ± 21.8 ng/mL to 121.4 ± 29.4 ng/mL, ECs: from 6.6 ± 4.5 cells/μL to 9.5 ± 6.2 cells/μL, both p < 0.01; results were not different between exercise modalities and negatively related to TAC concentrations post-exercise. HPC proportions and self-renewal ability were negatively, while EC concentrations were positively associated with circulating hyaluronan concentrations.ConclusionsThese results highlight the importance of the antioxidative system to prevent the endothelium from acute exercise-induced vascular injury – independent of exercise modality – in well-trained participants. Endothelial-cell repair is associated with hyluronan signaling, possibly a similar mechanism as in wound repair.