Discrimination and anatomical mapping of PET-positive lesions: comparison of CT attenuation-corrected PET images with coregistered MR and CT images in the abdomen

Purpose: PET/MR has the potential to become a powerful tool in clinical oncological imaging. The purpose of this prospective study was to evaluate the performance of a single T1-weighted (T1w) fat-suppressed unenhanced MR pulse sequence of the abdomen in comparison with unenhanced low-dose CT images to characterize PET-positive lesions. Methods: A total of 100 oncological patients underwent sequential whole-body 18F-FDG PET with CT-based attenuation correction (AC), 40mAs low-dose CT and two-point Dixon-based T1w 3D MRI of the abdomen in a trimodality PET/CT-MR system. PET-positive lesions were assessed by CT and MRI with regard to their anatomical location, conspicuity and additional relevant information for characterization. Results: From among 66 patients with at least one PET-positive lesion, 147 lesions were evaluated. No significant difference between MRI and CT was found regarding anatomical lesion localization. The MR pulse sequence used performed significantly better than CT regarding conspicuity of liver lesions (p < 0.001, Wilcoxon signed ranks test), whereas no difference was noted for extrahepatic lesions. For overall lesion characterization, MRI was considered superior to CT in 40% of lesions, equal to CT in 49%, and inferior to CT in 11%. Conclusion: Fast Dixon-based T1w MRI outperformed low-dose CT in terms of conspicuity and characterization of PET-positive liver lesions and performed similarly in extrahepatic tumour manifestations. Hence, under the assumption that the technical issue of MR AC for whole-body PET examinations is solved, in abdominal PET/MR imaging the replacement of low-dose CT by a single Dixon-based MR pulse sequence for anatomical lesion correlation appears to be valid and robus

Striatins as plaque molecules of zonulae adhaerentes in simple epithelia, of tessellate junctions in stratified epithelia, of cardiac composite junctions and of various size classes of lateral adherens junctions in cultures of epithelia- and carcinoma-derived cells

Proteins of the striatin family (striatins 1–4; sizes ranging from 90 to 110 kDa on SDS-polyacrylamide gel electrophoresis) are highly homologous in their amino acid sequences but can differ in their cell-type-specific gene expression patterns and biological functions. In various cell types, we have found one, two or three polypeptides of this evolutionarily old and nearly ubiquitous family of proteins known to serve as scaffold proteins for diverse protein complexes. Light and electron microscopic immunolocalization methods have revealed striatins in mammalian cell-cell adherens junctions (AJs). In simple epithelia, we have localized striatins as constitutive components of the plaques of the subapical zonulae adhaerentes of cells, including intestinal, glandular, ductal and urothelial cells and hepatocytes. Striatins colocalize with E-cadherin or E–N-cadherin heterodimers and with the plaque proteins α- and β-catenin, p120 and p0071. In some epithelia and carcinomas and in cultured cells derived therefrom, striatins are also seen in lateral AJs. In stratified epithelia and in corresponding squamous cell carcinomas, striatins can be found in plaques of some forms of tessellate junctions. Moreover, striatins are major plaque proteins of composite junctions (CJs; areae compositae) in the intercalated disks connecting cardiomyocytes, colocalizing with other CJ molecules, including plectin and ankyrin-G. We discuss the “multimodulator” scaffold roles of striatins in the initiation and regulation of the formation of various complex particles and structures. We propose that striatins are included in the diagnostic candidate list of proteins that, in the CJs of human hearts, can occur in mutated forms in the pathogeneses of hereditary cardiomyopathies, as seen in some types of genetically determined heart damage in boxer dogs.German-Israeli Foundation for Scientific Research and Development (GIF grant I-1098-43.11/2010

E–N-cadherin heterodimers define novel adherens junctions connecting endoderm-derived cells

Contradicting the “cadherin switch” model, mixed E-cadherin–N-cadherin heterodimeric adherens junctions are prevalent in a variety of endodermal cells and endoderm-derived tumors

The cell-cell junctions of mammalian testes: I. The adhering junctions of the seminiferous epithelium represent special differentiation structures

The seminiferous tubules and the excurrent ducts of the mammalian testis are physiologically separated from the mesenchymal tissues and the blood and lymph system by a special structural barrier to paracellular translocations of molecules and particles: the “blood–testis barrier”, formed by junctions connecting Sertoli cells with each other and with spermatogonial cells. In combined biochemical as well as light and electron microscopical studies we systematically determine the molecules located in the adhering junctions of adult mammalian (human, bovine, porcine, murine, i.e., rat and mouse) testis. We show that the seminiferous epithelium does not contain desmosomes, or “desmosome-like” junctions, nor any of the desmosome-specific marker molecules and that the adhering junctions of tubules and ductules are fundamentally different. While the ductules contain classical epithelial cell layers with E-cadherin-based adherens junctions (AJs) and typical desmosomes, the Sertoli cells of the tubules lack desmosomes and “desmosome-like” junctions but are connected by morphologically different forms of AJs. These junctions are based on N-cadherin anchored in cytoplasmic plaques, which in some subforms appear thick and dense but in other subforms contain only scarce and loosely arranged plaque structures formed by α- and β-catenin, proteins p120, p0071 and plakoglobin, together with a member of the striatin family and also, in rodents, the proteins ZO-1 and myozap. These N-cadherin-based AJs also include two novel types of junctions: the “areae adhaerentes”, i.e., variously-sized, often very large cell-cell contacts and small sieve-plate-like AJs perforated by cytoplasm-to-cytoplasm channels of 5–7 nm internal diameter (“cribelliform junctions”). We emphasize the unique character of this epithelium that totally lacks major epithelial marker molecules and structures such as keratin filaments and desmosomal elements as well as EpCAM- and PERP-containing junctions. We also discuss the nature, development and possible functions of these junctions.German-Israeli Foundation for Scientific Research and Development (GIF grant I-1098-43.11/2010

Transmembrane protein PERP is a component of tessellate junctions and of other junctional and non-junctional plasma membrane regions in diverse epithelial and epithelium-derived cells

Protein PERP (p53 apoptosis effector related to PMP-22) is a small (21.4 kDa) transmembrane polypeptide with an amino acid sequence indicative of a tetraspanin character. It is enriched in the plasma membrane and apparently contributes to cell-cell contacts. Hitherto, it has been reported to be exclusively a component of desmosomes of some stratified epithelia. However, by using a series of newly generated mono- and polyclonal antibodies, we show that protein PERP is not only present in all kinds of stratified epithelia but also occurs in simple, columnar, complex and transitional epithelia, in various types of squamous metaplasia and epithelium-derived tumors, in diverse epithelium-derived cell cultures and in myocardial tissue. Immunofluorescence and immunoelectron microscopy allow us to localize PERP predominantly in small intradesmosomal locations and in variously sized, junction-like peri- and interdesmosomal regions (“tessellate junctions”), mostly in mosaic or amalgamated combinations with other molecules believed, to date, to be exclusive components of tight and adherens junctions. In the heart, PERP is a major component of the composite junctions of the intercalated disks connecting cardiomyocytes. Finally, protein PERP is a cobblestone-like general component of special plasma membrane regions such as the bile canaliculi of liver and subapical-to-lateral zones of diverse columnar epithelia and upper urothelial cell layers. We discuss possible organizational and architectonic functions of protein PERP and its potential value as an immunohistochemical diagnostic marker

On the formation of lipid droplets in human adipocytes: the organization of the perilipin-vimentin cortex.

We report on the heterogeneity and diversity of lipid droplets (LDs) in early stages of adipogenesis by elucidating the cell and molecular biology of amphiphilic and cytoskeletal proteins regulating and stabilizing the generation of LDs in human adipose cells. A plethora of distinct and differently sized LDs was detected by a brief application of adipocyte differentiation medium and additional short treatment with oleic acid. Using these cells and highly specific antibodies for LD-binding proteins of the perilipin (PLIN) family, we could distinguish between endogenously derived LDs (endogenous LDs) positive for perilipin from exogenously induced LDs (exogenous LDs) positive for adipophilin, TIP47 and S3-12. Having optimized these stimulation conditions, we used early adipogenic differentiation stages to investigate small-sized LDs and concentrated on LD-protein associations with the intermediate-sized filament (IF) vimentin. This IF protein was described earlier to surround lipid globules, showing spherical, cage-like structures. Consequently - by biochemical methods, by immunofluorescence microscopy and by electron- and immunoelectron microscopy - various stages of emerging lipid globules were revealed with perilipin as linking protein between LDs and vimentin. For this LD-PLIN-Vimentin connection, a model is now proposed, suggesting an interaction of proteins via opposed charged amino acid domains respectively. In addition, multiple sheaths of smooth endoplasmic reticulum cisternae surrounding concentrically nascent LDs are shown. Based on our comprehensive localization studies we present and discuss a novel pathway for the LD formation

Discrimination and anatomical mapping of PET-positive lesions: comparison of CT attenuation-corrected PET images with coregistered MR and CT images in the abdomen

PURPOSE: PET/MR has the potential to become a powerful tool in clinical oncological imaging. The purpose of this prospective study was to evaluate the performance of a single T1-weighted (T1w) fat-suppressed unenhanced MR pulse sequence of the abdomen in comparison with unenhanced low-dose CT images to characterize PET-positive lesions. METHODS: A total of 100 oncological patients underwent sequential whole-body (18)F-FDG PET with CT-based attenuation correction (AC), 40 mAs low-dose CT and two-point Dixon-based T1w 3D MRI of the abdomen in a trimodality PET/CT-MR system. PET-positive lesions were assessed by CT and MRI with regard to their anatomical location, conspicuity and additional relevant information for characterization. RESULTS: From among 66 patients with at least one PET-positive lesion, 147 lesions were evaluated. No significant difference between MRI and CT was found regarding anatomical lesion localization. The MR pulse sequence used performed significantly better than CT regarding conspicuity of liver lesions (p < 0.001, Wilcoxon signed ranks test), whereas no difference was noted for extrahepatic lesions. For overall lesion characterization, MRI was considered superior to CT in 40 % of lesions, equal to CT in 49 %, and inferior to CT in 11 %. CONCLUSION: Fast Dixon-based T1w MRI outperformed low-dose CT in terms of conspicuity and characterization of PET-positive liver lesions and performed similarly in extrahepatic tumour manifestations. Hence, under the assumption that the technical issue of MR AC for whole-body PET examinations is solved, in abdominal PET/MR imaging the replacement of low-dose CT by a single Dixon-based MR pulse sequence for anatomical lesion correlation appears to be valid and robust