Atypical chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroids (CLIPPERS), primary angiitis of the CNS mimicking CLIPPERS or overlap syndrome? A case report

A novel type of encephalomyelitis was first described as chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in 2010 and few additional patients were reported since then. Partially due to its unknown aetiology and a lack of pathognomonic features some have suggested that CLIPPERS may not represent a distinct disease, but rather a syndrome with different underlying aetiologies. Here we report a 49-year-old German female who presented with a number of clinical and paraclinical features described as typical for CLIPPERS, while additionally showing symptoms and findings compatible with primary angiitis of the CNS (PACNS). This case may establish a previously unnoted link between two poorly understood autoimmune conditions of the CNS.     

Oligodendroglial lineage cells express nuclear p57kip2 in multiple sclerosis lesions

Impaired remyelination in multiple sclerosis (MS) might be due to the failure of oligodendrocyte precursor cells (OPC) to differentiate into myelinating oligodendrocytes. Animal experimental data have shown that p57kip2 inhibits oligodendroglial differentiation, indicating that this factor could contribute to remyelination failure. This study investigates oligodendroglial p57kip2 expression and its association with remyelination in MS lesions. To analyze the potential association of p57kip2 expression with human oligodendroglial maturation, double immunofluorescence staining was performed on brain tissue from 30 MS patients and 20 controls. Anti‐p57kip2 antibody was combined with either anti‐Nogo‐A to label mature oligodendrocytes or anti‐Olig2 antibodies to identify immature OPCs. We evaluated MS lesions with or without remyelination, the periplaque white matter (PPWM) as well as control white matter (WM). p57kip2‐expressing cells were assessed and correlated with the extent of remyelination. Most Nogo‐A‐positive oligodendrocytes (range, 87–98%) and all Olig2^strong‐positive OPCs expressed p57kip2 in MS lesions, in the PPWM and in control WM. p57kip2 expression in oligodendrocytes and OPCs were similar in MS lesions with remyelination compared to MS lesions lacking remyelination. Interestingly, all oligodendroglial lineage cells showed nuclear p57kip2 expression only, with mature oligodendrocytes expressing p57kip2 at low or intermediate levels and OPCs featuring strong expression levels, indicating that this factor may be dynamically expressed during maturation processes. Therefore, p57kip2 appears to be widely expressed in the human oligodendroglial lineage, and potential beneficial effects on remyelination in the MS brain are not based on subcellular p57kip2 localization shifts, as suggested by previous animal experiments. GLIA 2013;61:1250–1260     

EAACI position paper on diet diversity in pregnancy,infancy and childhood: Novel concepts and implications for studies in allergy and asthma

To fully understand the role of diet diversity on allergy outcomes and to set standards for conducting research in this field, the European Academy of Allergy and Clinical Immunology Task Force on Diet and Immunomodulation has systematically explored the association between diet diversity and allergy outcomes. In addition, a detailed narrative review of information on diet quality and diet patterns as they pertain to allergic outcomes is presented. Overall, we recommend that infants of any risk category for allergic disease should have a diverse diet, given no evidence of harm and some potential association of benefit in the prevention of particular allergic outcomes. In order to harmonize methods for future data collection and reporting, the task force members propose relevant definitions and important factors for consideration, when measuring diet diversity in the context of allergy. Consensus was achieved on practice points through the Delphi method. It is hoped that the definitions and considerations described herein will also enable better comparison of future studies and improve mechanistic studies and pathway analysis to understand how diet diversity modulates allergic outcomes.     

Platelet receptor interplay regulates collagen-induced thrombus formation in flowing human blood

The platelet glycoproteins (GPs) Ib, integrin alpha(2)beta(1), and GPVI are considered central to thrombus formation. Recently, their relative importance has been re-evaluated based on data from murine knockout models. To examine their relationship during human thrombus formation on collagen type I fibers at high shear (1000 s(-1)), we tested a novel antibody against GPVI, an immunoglobulin single-chain variable fragment, 10B12, together with specific antagonists for GPIb alpha (12G1 Fab(2)) and alpha(2)beta(1) (6F1 mAb or GFOGER-GPP peptide). GPVI was found to be crucial for aggregate formation, Ca(2+) signaling, and phosphatidylserine (PS) exposure, but not for primary adhesion, even with more than 97% receptor blockade. Inhibiting alpha(2)beta(1) revealed its involvement in regulating Ca(2+) signaling, PS exposure, and aggregate size. Both GPIb alpha and alpha(2)beta(1) contributed to primary adhesion, showing overlapping function. The coinhibition of receptors revealed synergism in thrombus formation: the coinhibition of adenosine diphosphate (ADP) receptors with collagen receptors further decreased adhesion and aggregation, and, crucially, the complete eradication of thrombus formation required the coinhibition of GPVI with either GPIb alpha or alpha(2)beta(1). In summary, human platelet deposition on collagen depends on the concerted interplay of several receptors: GPIb in synergy with alpha(2)beta(1) mediating primary adhesion, reinforced by activation through GPVI, which further regulates the thrombus formation.     

Protein Quality in Perspective: A Review of Protein Quality Metrics and Their Applications

For design of healthy and sustainable diets and food systems, it is important to consider not only the quantity but also the quality of nutrients. This is particularly important for proteins, given the large variability in amino acid composition and digestibility between dietary proteins. This article reviews measurements and metrics in relation to protein quality, but also their application. Protein quality methods based on concentrations and digestibility of individual amino acids are preferred, because they do not only allow ranking of proteins, but also assessment of complementarity of protein sources, although this should be considered only at a meal level and not a diet level. Measurements based on ileal digestibility are preferred over those on faecal digestibility to overcome the risk of overestimation of protein quality. Integration of protein quality on a dietary level should also be done based on measurements on an individual amino acid basis. Effects of processing, which is applied to all foods, should be considered as it can also affect protein quality through effects on digestibility and amino acid modification. Overall, protein quality data are crucial for integration into healthy and sustainable diets, but care is needed in data selection, interpretation and integration.     

Enzyme Immunoassay Detecting Teichoic and Lipoteichoic Acids versus Cerebrospinal Fluid Culture and Latex Agglutination for Diagnosis of Streptococcus pneumoniae Meningitis

A newly developed enzyme immunoassay (EIA) was used to detect the presence of pneumococcal teichoic and lipoteichoic acids in cerebrospinal fluid (CSF) from patients with Streptococcus pneumoniae meningitis who were being treated with antibiotics. All initial CSF samples, which on culture grew S. pneumoniae, were positive in the EIA. A total of 14 subsequent culture-negative samples gave clear signals in the EIA up to day 15 after the onset of antibiotic treatment. For 11 CSF specimens, culture, microscopy, and latex agglutination were negative while the EIA detected pneumococcal antigens. The EIA did not react either with CSF of patients with meningitis caused by bacteria other than S. pneumoniae or by viral pathogens. In conclusion, this EIA can be a valuable tool for the diagnosis of S. pneumoniae meningitis from CSF samples in cases in which prior antimicrobial therapy minimizes the usefulness of culture or other antigen detection tests.     

Strongly reduced expression of the cell cycle inhibitor p27 in endometrial neoplasia

 In the present study we investigated the expression of the cell cycle inhibitor p27 in endometrial neoplasia using immunohistochemistry with a p27-specific antibody. Expression of p27 in endometrial carcinomas was compared with expression in the normal endometrium throughout the cycle. Normal endometrial cells showed strong nuclear expression of p27. Expression was present throughout the cycle and was stronger during the secretory phase. We found strongly reduced or abolished expression of p27 in endometrial carcinoma (85.3% of cases). The 41 tumours analysed were classified according to p27 staining intensity and percentage of positive cells into the following categories of p27 expression: negative/very low (56.0%); low (29.3%); moderate (14.7%) and high (0.0%). All the p27-positive tumours were well-differentiated endometrioid carcinomas of malignancy grade G1. Comparison with the p53 status showed that all tumours with strong p53 expression had low/negative p27 staining, while those that were positive for p27 had negative/low p53 staining. Reduced or absent p27 levels were also observed by Western blot analysis both in tumour samples and in HEC-1B endometrial adenocarcinoma cells. It thus seems that p27 expression is essential for the control of normal endometrial proliferation, and reduced or absent p27 expression may be an important step in endometrial carcinogenesis. Received: 23 September 1998 / Accepted: 7 January 1999     

No ON-OFF maps in supragranular layers of ferret visual cortex

Primary visual cortex contains functional maps of a number of stimulus properties including ocular dominance, orientation, direction, color, and spatial frequency. These maps must be organized with respect to each other and to a single continuous retinotopic map of visual space such that each stimulus parameter is represented at each point in space. In the ferret, geniculo-cortical inputs to cortical layer IV are segregated into ON- and OFF-center patches, suggesting the possibility that there might be an additional cortical map in this species. We have used optical imaging of intrinsic signals to search for ON-OFF maps in ferret visual cortical cells and have found none. This suggests that the high degree of ON-OFF segregation seen subcortically in the ferret may play a role in the development of visual cortical receptive fields rather than in adult cortical function.     

Epidemiology of bacteria and viruses in the respiratory tract of humans and domestic pigs

Bacteria and viruses were analysed in the upper respiratory tract of symptomatic pig farmers and their domestic pigs. Eighty six human nasal and 495 (50 pools) porcine snout swabs were collected in Schleswig-Holstein, Germany. Staphylococcus (S.) aureus (62.8%, 54/86), human rhino- and coronaviruses (HRV, 29.1%, 25/86; HCoV, 16.3%, 14/86) were frequently detected in humans, while Haemophilus parasuis (90.0%, 45/50), Mycoplasma hyorhinis (78.6%, 11/14), Enterovirus G (EV-G, 56.0%, 28/50) and S. aureus (36.0%, 18/50), respectively, were highly prevalent in pigs. The detection of S. aureus in human follow-up samples indicates a carrier status. The methicillin-resistant phenotype (MRSA) was identified in 33.3% (18/54) of nasal swabs and in one of 18 (5.6%) pooled snout swabs that were tested positive for S. aureus. Strains were indicative of the livestock-associated clonal complex CC398, with t011 being the most common staphylococcal protein A type. Enterobacterales and non-fermenters were frequently isolated from swabs. Their detection in follow-up samples suggests a carrier status. All were classified as being non-multiresistant. There was no example for cross-species transmission of viruses. In contrast, transmission of S. aureus through occupational contact to pigs seems possible. The study contributes to the ‘One Health’ approach.