Altered expression of claudin family proteins in Alzheimer's disease and vascular dementia brains.

Claudins (Cls) are a multigene family of transmembrane proteins with different tissue distribution, which have an essential role in the formation and sealing capacity of tight junctions (TJs). At the level of the blood-brain barrier (BBB), TJs are the main molecular structures which separate the neuronal milieu from the circulatory space, by a restriction of the paracellular flow of water, ions and larger molecules into the brain. Different studies suggested recently significant BBB alterations in both vascular and degenerative dementia types.

Key signaling molecules in pituitary tumors.

In pituitary tumorigenesis there is cross-talk between fine deregulation of intracellular pathways and complex microenvironmental factors, processes that can be modulated at various levels. The signaling pathways of growth, angiogenic factors and hormones are intricate; therefore, alterations induced upon node-molecules can lead to aberrant proliferation. The demonstrated overactivity of AKT and MAPK pathways qualifies them as valuable targets for inhibition mediated by somatostatin analogues.

Biomarkers in the diagnosis and early detection of pancreatic cancer.

Background: Pancreatic cancer, owing to its raising incidence and aggressiveness, is a major challenge, both for research and for clinical management. As pancreatic cancer has a complex pathophysiology, in addition to improving the methods of early diagnosis, sensitive and specific biomarkers are a prerequisite.

Objective: As there is no specific tumor marker for pancreatic cancer diagnosis, extensive genomics/transcriptomics and proteomics studies have been developed with the aim of finding candidate markers and contributing to high-throughput systems for large cohort screening.

Human epicardium: ultrastructural ancestry of mesothelium and mesenchymal cells.

The human sub-epicardial area contains an unexplored cellular population under a layer of mesothelial cells. Transmission electron microscopy revealed the existence of interstitial Cajal-like cells (ICLCs), isolated smooth muscle cells (iSMC) and mesenchymal cells besides other well-known cells. The presence of iSMC in the sub-epicardial space is quite unique and could explain why epicardial-derived cells isolated from human epicardium generate smooth muscle cells in culture.

Pancreatic expression of DOG1: a novel gastrointestinal stromal tumor (GIST) biomarker.

The cDNA microarray gene profile of gastrointestinal stromal tumors (GISTs) revealed that DOG1 (TMEM16A) gene was mostly expressed in these neoplasms. Immunohistochemically, DOG1 protein was found positive in a significant proportion of GISTs. However, normal tissues' expression of DOG1 is not yet completely studied.

Blood-brain barrier alterations in ageing and dementia.

The current pathogenic scenarios of different types of dementia are based on a number of common mechanisms of neurodegeneration, such as accumulation of abnormal proteins (within or outside cells), mitochondrial dysfunction and oxidative stress, calcium homeostasis dysregulation, early synaptic disconnection and late apoptotic cell death. Ageing itself is associated with mild cognitive deterioration, probably due to subtle multifactorial changes resulting in a global decrease of a functional brain reserve. Increased age is a risk factor for neurodegeneration and key pathological features of dementia can also be found in aged brains.

Biomarkers of metastatic melanoma.

Melanoma, one of the most aggressive forms of human cancer, has undergone an alarming increase in incidence in recent years. Early detection is a prerequisite for proper diagnosis and therapy orientation. Soluble biomarkers are an important tool for early diagnosis.

Myocardial interstitial Cajal-like cells (ICLC) in caveolin-1 KO mice.

Abstract We compared, by transmission electron microscopy (TEM), the ultrastructure of interstitial Cajal-like cells (ICLC) in normal mammalian myocardium versus caveolin-1 null mice. TEM showed that myocardial ICLCs of caveolin-1-deficient mice retain their main ultrastructural characteristics, for example, location among cardiomyocytes, close vicinity to nerves and/or blood capillaries, specialized cell-to-cell junctions, presence of 2-3 typical processes, which are very long (several tens of micrometres), but are very thin (0.1-0.

Caveolin-1 overexpression correlates with tumour progression markers in pancreatic ductal adenocarcinoma.

The assessment of caveolin-1 (Cav-1) as a marker of tumor aggressiveness in pancreatic ductal adenocarcinoma (PDAC). In this study, we examined the expression of Cav-1 in 34 human PDAC tissue samples and the associated peritumoral tissues by immunohistochemistry and western blot. Additionally, we correlated Cav-1 expression with other tissue (Ki-67, p53) and serum (CA 19-9) tumor markers.

Angiocentric glioma: presentation of two cases with dissimilar histology.

Objective And Importance: Angiocentric glioma (AG) is a recently described tumor of the brain which was included as a distinct entity in the 2007 WHO classification. To date only 26 cases have been reported in the literature. We describe two additional cases of this possibly confusing lesion of the brain.

Preliminary study on the immunologic background of good clinical outcome in rheumatoid arthritis patients after one month therapy with leflunomide.

This preliminary study focuses on early peripheral cellular immune changes after 1 month therapy with leflunomide, in 18 patients with severe rheumatoid arthritis, previously treated with methotrexate. A good clinical outcome of disease was documented and we showed that a particular target of short-time leflunomide therapy in rheumatoid arthritis was the peripheral innate immune system (NK cells and the population of granulocytes developing phagocytosis and superoxide anion production when challenged ex vivo with zymosan particles). Meanwhile, the high inter-individual variability of adaptive immunity required data analysis in subgroups of patients.

Low basal levels of circulating adiponectin in patients undergoing coronary stenting predict in-stent restenosis, independently of basal levels of inflammatory markers: lipoprotein associated phospholipase A2, and myeloperoxidase.

Objective: The aim of this study was to find a pre-interventional marker with the capacity to predict in-stent restenosis (ISR). Considering the anti-atherosclerotic role of adiponectin (APO), an adipocytokine with anti-inflammatory, anti-proliferative, anti-oxidative and anti-thrombotic properties, low plasma levels of APO might be correlated with the risk of ISR. We investigated the correlations between the plasma levels of APO and two markers of inflammation: lipoprotein associated phospholipase A2 (Lp-PLA2) and myeloperoxidase (MPO).

Assessment of soluble angiogenic markers in pancreatic cancer.

Unlabelled: Angiogenic markers such as VEGF/basic FGF (bFGF) can enlarge the diagnostic biomarkers panel for pancreatic cancer.

Materials & Methods: Serum samples from 32 stage I-IV pancreatic cancer patients and 20 controls were analyzed for soluble VEGF/bFGF by ELISA and xMAP array.

Results: VEGF/bFGF serum levels were significantly increased in patients compared with controls (p < 0.

Interstitial Cajal-like cells (ICLC) in myocardial sleeves of human pulmonary veins.

We present here evidence for the existence of a new type of interstitial cell in human myocardial sleeves of pulmonary veins: interstitial Cajal-like cell (ICLC). This cell fulfils the criteria for positive diagnosis of ICLC, including CD 117/c-kit positivity. Transmission electron microscopy revealed typical ICLC with 2 or 3 very long processes (several tens of mm) suddenly emerging from the cellular body.

Myocardial stunning. Morphological studies in acute experimental ischemia and intraoperatory myocardial biopsies.

Myocardial stunning represent a consequence of brief ischemia with reversible regional contractile dysfunction dependent persist from minute to days after reperfusion, despite the absence of irreversible damage and restoration of coronary blood flow. The evolution of these new ischemic entity were described by experimental acute ischemia and repeated intraoperatory myocardial biopsies effectuated near 200 patients with heart disease, excluding those with cardiac failure and atrial fibrillation. Using histological histoenzymological and particularly ultrastructural methods, only reversible mitochondrial and sarcoplasmatic reticulum lesions, slight glycogen granules depletions and sporadical dissociation of myofilaments by edema were seen.

Electron microscope tomography: further demonstration of nanocontacts between caveolae and smooth muscle sarcoplasmic reticulum.

A spatial relationship between caveolae and sarcoplasmic reticulum (SR) in smooth muscle cells (SMC) was previously reported in computer-assisted three-dimensional reconstruction from transmission electron microscope serial sections. The knowledge of the three-dimensional organization of the cortical space of SMC is essential to understand caveolae function at the cellular level. Cellular tomography using transmission electron microscopy tomography (EMT) is the only available technology to reliably chart the inside of a cell and is therefore an essential technology in the study of organellar nanospatial relationships.

Interstitial Cajal-like cells (ICLC) as steroid hormone sensors in human myometrium: immunocytochemical approach.

Expression of estrogen (ER) and progesterone (PR) receptors was investigated in cultured human normal myometrial cells (non-pregnant uterus, fertile period). The ER and PR expression was studied by immunohistochemistry and immunofluorescence on either myocytes or interstitial Cajal-like cells (ICLC). Only those cells double immunostained for c-kit and steroid receptors were considered as ICLC.

Caveolar nanospaces in smooth muscle cells.

Caveolae, specialized membrane nanodomains, have a key role in signaling processes, including calcium handling in smooth muscle cells (SMC). We explored the three-dimensional (3D) architecture of peripheral cytoplasmic space at the nanoscale level and the close spatial relationships between caveolae, sarcoplasmic reticulum (SR), and mitochondria, as ultrastructural basis for excitation-contraction coupling system and, eventually, for excitation-transcription coupling. About 150 electron micrographs of SMC showed that superficial SR and peripheral mitochondria are rigorously located along the caveolar domains of plasma membrane, alternating with plasmalemmal dense plaques.

Insights into the interstitium of ventricular myocardium: interstitial Cajal-like cells (ICLC).

We have previously described interstitial Cajal-like cells (ICLC) in human atrial myocardium. Several complementary approaches were used to verify the existence of ICLC in the interstitium of rat or human ventricular myocardium: primary cell cultures, vital stainings (e.g.

p53 protein and bcl-2 expression in glioblastomas. Pathological correlations in a comprehensive series.

p53 and bcl-2 are two well-known antiapoptotic factors associated with gliomas, and mostly astrocytic tumors. In the present study we assessed, by immunohistochemistry, the expression of these two factors in a series of 50 glioblastomas. The correlations between their expression and several tumor-related factors (age, location, recurrence, proliferating potential) were investigated.

Uncommon pattern in soft tissues epithelioid sarcoma.

Unlabelled: Epithelioid sarcoma (ES) is a rare tumor, but extremely versatile, simulating easily both clinically and morphologically multiple benign lesions as granulomas and malignant tumors as achromic melanomas or carcinomas. Especially the histological aspects are suggesting for an epithelial tumor. The atypical biological behavior of tumor is conferred by: a propensity for lymph nodes metastases, large dimensions of tumor, unusual localizations.

Paraganglioma of the cerebellopontine angle. Case presentation and pathological considerations.

Paragangliomas (glomus tumors) arise from the extra-adrenal neuroendocrine system. They are benign but locally aggressive tumors, causing bone destruction and compression related symptoms. We present a case of paraganglioma of the cerebellopontine angle.

Interstitial Cajal-like cells (ICLC) in human resting mammary gland stroma. Transmission electron microscope (TEM) identification.

We have previously shown the existence of ICLC in human resting mammary gland stroma by means of methylene blue (vital) staining and c-kit immunopositivity (immunofluorescence and immunohistochemistry). In addition, we reported the phenotype characteristics of these ICLC in vitro (primary cell cultures). Since the identification of ICLC outside the gut requires, at this moment, the obligatory use of TEM, we used this technique and provide unequivocal evidence for the presence of ICLC in the intralobular stroma of human resting mammary gland.

Ultrastructural defects of the glomerular basement membranes associated with primary glomerular nephropathies.

It is generally accepted that a glomerular basement membrane (GBM) thinner than 200 nm should be considered below normal. When this abnormality has a global and diffuse distribution, the associated clinical condition is a benign familial hematuria related to mutations of the COL4A4/COL4A3 genes, or an Alport syndrome. More often the GBM defects display a focal and segmental pattern, too small to express a thin glomerular basement membrane disease.

Imbalance of peripheral B lymphocytes and NK cells in rheumatoid arthritis.

The study was focused on several cellular immune disorders correlated with the imbalance between peripheral blood B lymphocytes and NK cells in severe rheumatoid arthritis. By flow cytometry we calculated the proportions of T, T helper, T cytotoxic/suppressor, B lymphocytes and natural killer cells in peripheral blood. The mitogen-induced proliferation of peripheral lymphocytes was measured by tritium-labeled uridine incorporation.