Human intestinal M cells exhibit enterocyte-like intermediate filaments

Background—The derivation and ultrastructuralcomposition of M cells covering the lymphoid follicles of Peyer'spatches is still unknown. Results from different animal models haveshown that there are species specific differences in the composition ofintermediate filaments between M cells and neighbouring enterocytes. Little is known, however, about intermediate filaments of human M cells.
Aims—To compare components of the cytoskeleton ofhuman M cells with those of adjacent absorptive enterocytes.
Methods—The expression and localisation ofdifferent cytokeratins, vimentin, and desmin in M cells was determinedon follicle associated epithelia of human appendix usingimmunohistochemistry and immunogold electron microscopy.
Results—Cytokeratins specific for humanintestinal epithelial cells such as cytokeratins 8, 18, 19, and 20 wereexpressed in both absorptive enterocytes and M cells with nodifferences in intensity and cellular distribution between both celltypes. Vimentin and desmin, tissue specific markers of eithermesenchymal or myogenic cells, as well as other cytokeratins were notdetectable in enterocytes or M cells.
Conclusion—This is the first study on thestructure of intermediate filaments in human intestinal M cells. Ourresults show that in contrast to several animal models, human M cellsapparently do not differ from adjacent enterocytes in the compositionof their intermediate filament cytoskeleton. The presence of enterocyte like cytokeratins and the absence of other cytokeratins as well as ofvimentin and desmin supports the hypothesis of an epithelial origin ofhuman intestinal M cells and suggests that M cells may derive fromdifferentiated enterocytes.

Keywords:human intestinal M cells; appendix; cytokeratin; intermediate filaments; follicle associated epithelium

     

Cytokeratin-Containing Globular Filamentous Bodies in Renal Oncocytoma

Eighty-four cortical neoplasms were studied for cytokeratin and vimentin expression by immunohis-tochemistry and for intermediate filament aggregates by electron microscopy. Twenty oncocytomas expressed cytokeratin, 16 in a distinctive punctate pattern. These same 16 tumors also contained small globular filamentous bodies (GFB) by electron microscopy. The GFB were characterized by a matrix of intermediate-sized filaments with incorporation of diverse cell organelles such as endoplasmic reticulum, lysosomes, mitochondria, and lipid. The GFB were not within a unit membrane. Although 11 of 64 carcinomas also contained intermediate filament aggregates, only 2 of these solely expressed cytokeratin, and this was restricted to a few cells in small foci. Small GFB were also present in 5 carcinomas by electron microscopy. Three mixed clear and granular cell carcinomas contained only rare cells, whereas 2 sarcomatoid carcinomas, both of rhabdoid cell phenotype, contained numerous GFB that coexpressed vimentin and cytokeratin. Cytokeratin-containing GFB are common in oncocytomas but are uncommon in carcinoma, and, when numerous, may provide a diagnostically useful immunohistochemical feature with which to distinguish oncocytoma from its carcinoma congeners.     

Determining an efficient deep brain stimulation target in essential tremor - Cohort study and review of the literature

IntroductionDeep brain stimulation (DBS) is a highly efficacious treatment for essential tremor (ET). Still, the optimal anatomical target in the (sub)thalamic area is a matter of debate. The aim of this study was to determine the optimal target of DBS for ET regarding beneficial clinical outcome and impact on activities of daily living as well as stimulation-induced side effects and compare it with previously published coordinates.MethodsIn 30 ET patients undergoing bilateral DBS, severity of tremor was assessed by blinded video ratings before and at 1-year follow-up with DBS ON and OFF. Tremor scores and reported side effects and volumes of tissue activated were used to create a probabilistic map of DBS efficiency and side effects.ResultsDBS was effective both in tremor suppression as well as in improving patient reported outcomes, which were positively correlated. The “sweet spot” for tremor suppression was located inferior of the VIM in the subthalamic area, close to the superior margin of the zona incerta. The Euclidean distance of active contacts to this spot as well as to 10 of 13 spots from the literature review was predictive of individual outcome. A cluster associated with the occurrence of ataxia was located in direct vicinity of the “sweet spot”.ConclusionOur findings suggest the highest clinical efficacy of DBS in the posterior subthalamic area, lining up with previously published targets likely representing the dentato-rubro-thalamic tract. Side effects may not necessarily indicate lead misplacement, but should encourage clinicians to employ novel DBS programing options.     

Development of somites,muscle, and skeleton is independent of signals from the wolffian duct

Background : In the vertebrate embryo, skeletal muscle and the axial skeleton arise from the somites. Patterning of the somites into the respective somite compartments, namely dermomyotome, myotome, and sclerotome, depends on molecular signals from neighboring structures, including surface ectoderm, neural tube, notochord, and lateral plate mesoderm. A potential role of the intermediate mesoderm, notably the Wolffian or nephric duct, in somite development is poorly understood. Results : We studied somite compartmentalization as well as muscular and skeletal development after surgical ablation of the early Wolffian duct anlage, which lead to loss of the Wolffian duct and absence of the mesonephros, whereas Pax2 expression in the nephrogenic mesenchyme was temporarily maintained. We show that somite compartments, as well as the somite derivatives, skeletal muscle and the cartilaginous skeleton, develop normally in the absence of the Wolffian duct. Conclusions : Our results indicate that development of the musculoskeletal system is independent of the Wolffian duct as a signaling center. Developmental Dynamics 242:941–948, 2013. © 2013 Wiley Periodicals, Inc.     

Echinococcus multilocularis in musk rat (Ondatra zibethicus): the first finding of the parasite in naturally infected rodent in the Slovak Republic

Summary Infection with the larval stage of Echinococcus multilocularis was diagnosed in musk rat (Ondatra zibethicus) in the Slovak Republic. At necropsy, massively enlarged liver with numbers of abscess-like lesions up to 1.5 cm in diameter was found. Histological examination shoved the presence of typical multivesicular cysts with multiple protoscoleces and typical laminated layer. Polymerase chain reaction confirmed the diagnosis. According to our knowledge, this is the first documentation of Echinococcus multilocularis in naturally infected rodent in territory of the Slovak Republic.     

Regenerative Potential of Human Schneiderian Membrane: Progenitor Cells and Epithelial‐Mesenchymal Transition

An innate osteogenic potential of the Schneiderian membrane (SM) is progressively assessed in studies ranging from non‐human species to human subjects. It has relevance for endosteal placement and osseointegration. Nestin‐expressing osteogenic progenitor cells are allegedly involved in bone formation and remodelling. Nestin phenotype was not assessed previously in human SM. We therefore aimed to fill that particular gap in the literature. Bioptic samples of human adult SM were obtained during surgery from eight adult patients, operated for non‐malignant pathologies. Immunohistochemistry on paraffin‐embedded tissue samples used primary antibodies against nestin, CD45, CD146, cytokeratin 7 (CK7), and alpha‐smooth muscle actin (α‐SMA). Nestin expression was consistently found in endothelial cells, and was scarcely encountered in pericytes, putative stromal stem/progenitor cells, as well as in glandular epithelial cells. Moreover, woven bone formation in the periosteal layer of the SM can also be regarded as evidence of the osteogenic potential of this membrane. Nestin and CD45 expression in cells of the primary bone supports the osteogenic potential of SM nestin‐expressing cells and a possible involvement of hematopoietic stem cells in maxillary sinus floor remodeling. CD146, a known inducer of epithelial‐mesenchymal transition (EMT), was expressed in epithelia, as was CK7. Isolated stromal cells were found expressing CD146, CK7 and α‐SMA, suggesting that regenerative processes happening in the SM may also involve processes of EMT which generate stem/progenitor cells. This study provides additional evidence for the regenerative potential of the Schneiderian membrane and identifies potential roles for cells of its stem niche in osteogenesis. Anat Rec, 298:2132–2140, 2015. © 2015 Wiley Periodicals, Inc.     

Bortezomib combined with low-dose cytarabine in Intermediate-2 and high risk myelodysplastic syndromes. A phase I/II Study by the GFM

Marrow cells from patients with higher-risk myelodysplastic syndrome (MDS) exhibit constitutive nuclear factor (NF)-κB activation. The proteasome inhibitor, bortezomib, has limited efficacy as a single agent in acute myeloid leukaemia. Its activity on leukaemic cell lines is potentiated by chemotherapy. We treated 43 higher-risk MDS patients with bortezomib (1·5 mg/m(2) , days 1, 4, 8 and 11) and low dose cytarabine arabinoside (LDAC; 10 mg/m(2) , then 20 mg/m(2) from days 1-14), every 28 d for four cycles. Median follow-up was 29·7 months. Responses were seen in 12 of the 43 patients (28%), including complete response (CR, n = 1), marrow-CR (n = 3), partial response (PR, n = 5) and haematological improvement (HI, n = 3). Responses were seen in 12 (36%) of the 33 previously untreated patients (11% CR, 13% PR, 2·5% HI), compared to none in the 12 previously treated patients (P < 0·01). Responders had better overall survival (median 18·2 vs. 10 months). One CR and 3 marrow-CRs were seen in patients with complex karyotypes. Main toxicity was haematological, responsible for infection in six patients and bleeding in 3. Three patients with Grade 1-2 pre-treatment haematotoxicity developed Grade 3-4 toxicity. Neuropathy was seen in 12% of patients. The addition of bortezomib to LDAC in higher-risk MDS may improve results obtained with LDAC alone, especially in patients with unfavourable karyotypes.