Protein induced by vitamin K absence or antagonist-II (PIVKA-II) specifically increased in Italian hepatocellular carcinoma patients

OBJECTIVE: As a marker for Hepatocellular Carcinoma (HCC), Protein Induced by Vitamin K Absence II (PIVKA-II) seems to be superior to alpha fetoprotein (AFP). To better characterize the role of PIVKA-II, both AFP and PIVKA-II have been measured in Italian patients with diagnosis of HCC compared with patients affected by non-oncological liver pathologies. MATERIALS AND METHODS: Sixty serum samples from patients with HCC, 60 samples from patients with benign liver disease and 60 samples obtained from healthy blood donors were included in the study. PIVKA-II and AFP were measured by LUMIPULSE(®) G1200 (Fujirebio-Europe, Belgium). We considered as PIVKA-II cutoff 70 mAU/ml (mean +3SD) of the values observed in healthy subjects. RESULTS: The evaluation of PIVKA-II showed a positivity of 70% in patients with HCC and 5% in patients with benign diseases (p < 0.0001) whereas high levels of AFP were observed in 55% of HCC patients and in 47% of patients with benign diseases. The combined Receiver Operating Characteristic (ROC) analysis of the two analytes revealed a higher sensitivity (75%) compared to those observed for the individual biomarkers. In conclusion, we demonstrate that as a marker for HCC, PIVKA-II is more specific for HCC and less prone to elevation during chronic liver diseases. CONCLUSIONS: The combination of the two biomarkers, evaluated by the ROC analysis, improved the specificity compared to a single marker. These data suggest that the combined analysis of the two markers could be a useful tool in clinical practice

Endocrine cells share expression of N-CAM with neurones

The reeent explosive interest in eell adhesion molecules (CAMs) is a direet eonsequence of the fundamental roles they are thought to play during early embryogenesis and tissue formation [1,2]. The most weIl known of them, studied independently under the names of N-CAM [3] (neural-CAM), 02 protein [4] and BSP-2 [5], has been shown to consist in brain of a family of three glyeoproteins of Mr 180000, 140000 and 120000 [6,7] which are implicated in neurone-neurone adhesion by a homophilie binding meehanism [8,9]. While N-CAM was originally considered to be limited to neurones in adult tissues, ultrastruetural immunoeytochemical studies have sinee provided unequivocal evidenee that glial cells, both astrocytes [6,10] and Schwann cells [11], also express N-CAM (see also [12,13]). Apart from a very limited expression by skeletal muscle at the neuromuscular junetion [14], its expression in the adult Correspondence address: O.K. Langley, Unite 44 de I'INSERM, and Centre de Neurochirnie du CNRS, 5 rue Blaise Pascal, 67084 Strasbourg Cedex, France has been largely though not exclusively considered to be limited to nervous tissues. N-CAM has been found in eertain eells outside the nervous system (e.g. chromaffin eells in the adrenal medulla [11]) but such eells are derived from the neural crest. Here we extend our previous observations on endocrine eells in the adrenal gland and investigate the possible expression of N-CAM by other endoerine eells whieh have a non-neural origin. The present results indieate a mueh wider distribution of N-CAM in adult tissues than has previously been supposed. N-CAM is shown by immunoeytoehemistry to be expressed by several endoerine eells of non-neural origin. Immunoehemieal data eonfirm the presenee of N-CAM determinants typical of brain in endoerine eells although the relative proportions differ markedly. In addition, in two of the tissues examined a lower molecular mass NCAM positive polypeptide was also detected

The role of Gpi-anchored axonal glycoproteins in neural development and neurological disorders.

This review article focuses on the Contactin (CNTN) subset of the Immunoglobulin supergene family (IgC2/FNIII molecules), whose components share structural properties (the association of Immunoglobulin type C2 with Fibronectin type III domains), as well as a general role in cell contact formation and axonal growth control. IgC2/FNIII molecules include 6 highly related components (CNTN 1-6), associated with the cell membrane via a Glycosyl Phosphatidyl Inositol (GPI)-containing lipid tail. Contactin 1 and Contactin 2 share ~50 (49.38)% identity at the aminoacid level. They are components of the cell surface, from which they may be released in soluble forms. They bind heterophilically to multiple partners in cis and in trans, including members of the related L1CAM family and of the Neurexin family Contactin-associated proteins (CNTNAPs or Casprs). Such interactions are important for organising the neuronal membrane, as well as for modulating the growth and pathfinding of axon tracts. In addition, they also mediate the functional maturation of axons by promoting their interactions with myelinating cells at the nodal, paranodal and juxtaparanodal regions. Such interactions also mediate differential ionic channels (both Na(+) and K(+)) distribution, which is of critical relevance in the generation of the peak-shaped action potential. Indeed, thanks to their interactions with Ankyrin G, Na(+) channels map within the nodal regions, where they drive axonal depolarization. However, no ionic channels are found in the flanking Contactin1-containing paranodal regions, where CNTN1 interactions with Caspr1 and with the Ig superfamily component Neurofascin 155 in cis and in trans, respectively, build a molecular barrier between the node and the juxtaparanode. In this region K(+) channels are clustered, depending upon molecular interactions with Contactin 2 and with Caspr2. In addition to these functions, the Contactins appear to have also a role in degenerative and inflammatory disorders: indeed Contactin 2 is involved in neurodegenerative disorders with a special reference to the Alzheimer disease, given its ability to work as a ligand of the Alzheimer Precursor Protein (APP), which results in increased Alzheimer Intracellular Domain (AICD) release in a γ-secretase-dependent manner. On the other hand Contactin-1 drives Notch signalling activation via the Hes pathway, which could be consistent with its ability to modulate neuroinflammation events, and with the possibility that Contactin 1-dependent interactions may participate to the pathogenesis of the Multiple Sclerosis and of other inflammatory disorders

Molecular and cellular substrates for the Friedreich Ataxia. significance of contactin expression and of antioxidant administration

In this study, the neural phenotype is explored in rodent models of the spinocerebellar disorder known as the Friedreich Ataxia (FA), which results from mutations within the gene encoding the Frataxin mitochondrial protein. For this, the M12 line, bearing a targeted mutation, which disrupts the Frataxin gene exon 4 was used, together with the M02 line, which, in addition, is hemizygous for the human Frataxin gene mutation (Pook transgene), implying the occurrence of 82–190 GAA repeats within its first intron. The mutant mice phenotype was compared to the one of wild type littermates in regions undergoing differential profiles of neurogenesis, including the cerebellar cortex and the spinal cord by using neuronal (β-tubulin) and glial (Glial Fibrillary Acidic Protein) markers as well as the Contactin 1 axonal glycoprotein, involved in neurite growth control. Morphological/morphometric analyses revealed that while in Frataxin mutant mice the neuronal phenotype was significantly counteracted, a glial upregulation occurred at the same time. Furthermore, Contactin 1 downregulation suggested that changes in the underlying gene contributed to the disorder pathogenesis. Therefore, the FA phenotype implies an alteration of the developmental profile of neuronal and glial precursors. Finally, epigallocatechin gallate polyphenol administration counteracted the disorder, indicating protective effects of antioxidant administration

Artificial intelligence in clinical endoscopy: Insights in the field of videomics

Artificial intelligence is being increasingly seen as a useful tool in medicine. Specifically, these technologies have the objective to extract insights from complex datasets that cannot easily be analyzed by conventional statistical methods. While promising results have been obtained for various -omics datasets, radiological images, and histopathologic slides, analysis of videoendoscopic frames still represents a major challenge. In this context, videomics represents a burgeoning field wherein several methods of computer vision are systematically used to organize unstructured data from frames obtained during diagnostic videoendoscopy. Recent studies have focused on five broad tasks with increasing complexity: quality assessment of endoscopic images, classification of pathologic and nonpathologic frames, detection of lesions inside frames, segmentation of pathologic lesions, and in-depth characterization of neoplastic lesions. Herein, we present a broad overview of the field, with a focus on conceptual key points and future perspectives

Perioperative Minimal Induction Therapy: A Further Step toward More Effective Immunosuppression in Transplantation

Dual induction with low doses of rabbit anti-human thymoglobulin (RATG) and basiliximab effectively and safely prevented allograft rejection in high-risk renal transplant recipients. To assess whether treatment timing affects efficacy and tolerability, in this single-center, matched-cohort study, we compared posttransplant outcomes in 25 patients and 50 gender-, age-, and treatment-matched reference patients induced with the same course of 7 daily RATG infusions (0.5 mg/kg/day) started before or after engraftment, respectively. All subjects received basiliximab (20 mg) before and 4 days after transplantation, withdrew steroids within 6 days after surgery, and were maintained on steroid-free immunosuppression with cyclosporine and mycophenolate mofetil or azathioprine. Over 12 months after transplant, 1 patient (4%) and 13 reference patients (26%) had acute rejection episodes. One patient and 5 reference-patients required dialysis therapy because of delayed graft function. In all patients circulating CD4+ and CD8+ T lymphocytes were fully depleted before engraftment. Both treatments were well tolerated. In kidney transplantation, perioperative RATG infusion enhances the protective effect of low-dose RATG and basiliximab induction against graft rejection and delayed function, possibly because of more effective inhibition of early interactions between circulating T cells and graft antigens

Instance segmentation of upper aerodigestive tract cancer: site-specific outcomes

Objective. To achieve instance segmentation of upper aerodigestive tract (UADT) neoplasms using a deep learning (DL) algorithm, and to identify differences in its diagnostic performance in three different sites: larynx/hypopharynx, oral cavity and oropharynx.Methods. A total of 1034 endoscopic images from 323 patients were examined under narrow band imaging (NBI). The Mask R-CNN algorithm was used for the analysis. The dataset split was: 935 training, 48 validation and 51 testing images. Dice Similarity Coefficient (Dsc) was the main outcome measure.Results. Instance segmentation was effective in 76.5% of images. The mean Dsc was 0.90 & PLUSMN; 0.05. The algorithm correctly predicted 77.8%, 86.7% and 55.5% of lesions in the larynx/hypopharynx, oral cavity, and oropharynx, respectively. The mean Dsc was 0.90 & PLUSMN; 0.05 for the larynx/hypopharynx, 0.60 & PLUSMN; 0.26 for the oral cavity, and 0.81 & PLUSMN; 0.30 for the oropharynx. The analysis showed inferior diagnostic results in the oral cavity compared with the larynx/hypopharynx (p < 0.001). Conclusions. The study confirms the feasibility of instance segmentation of UADT using DL algorithms and shows inferior diagnostic results in the oral cavity compared with other anatomic areas

The Cerebellar Dopaminergic System

In the central nervous system (CNS), dopamine (DA) is involved in motor and cognitive functions. Although the cerebellum is not been considered an elective dopaminergic region, studies attributed to it a critical role in dopamine deficit-related neurological and psychiatric disorders [e.g., Parkinson's disease (PD) and schizophrenia (SCZ)]. Data on the cerebellar dopaminergic neuronal system are still lacking. Nevertheless, biochemical studies detected in the mammalians cerebellum high dopamine levels, while chemical neuroanatomy studies revealed the presence of midbrain dopaminergic afferents to the cerebellum as well as wide distribution of the dopaminergic receptor subtypes (DRD1-DRD5). The present review summarizes the data on the cerebellar dopaminergic system including its involvement in associative and projective circuits. Furthermore, this study also briefly discusses the role of the cerebellar dopaminergic system in some neurologic and psychiatric disorders and suggests its potential involvement as a target in pharmacologic and non-pharmacologic treatments

A Spontaneous Mutation in Contactin 1 in the Mouse

Mutations in the gene encoding the immunoglobulin-superfamily member cell adhesion molecule contactin1 (CNTN1) cause lethal congenital myopathy in human patients and neurodevelopmental phenotypes in knockout mice. Whether the mutant mice provide an accurate model of the human disease is unclear; resolving this will require additional functional tests of the neuromuscular system and examination of Cntn1 mutations on different genetic backgrounds that may influence the phenotype. Toward these ends, we have analyzed a new, spontaneous mutation in the mouse Cntn1 gene that arose in a BALB/c genetic background. The overt phenotype is very similar to the knockout of Cntn1, with affected animals having reduced body weight, a failure to thrive, locomotor abnormalities, and a lifespan of 2–3 weeks. Mice homozygous for the new allele have CNTN1 protein undetectable by western blotting, suggesting that it is a null or very severe hypomorph. In an analysis of neuromuscular function, neuromuscular junctions had normal morphology, consistent with previous studies in knockout mice, and the muscles were able to generate appropriate force when normalized for their reduced size in late stage animals. Therefore, the Cntn1 mutant mice do not show evidence for a myopathy, but instead the phenotype is likely to be caused by dysfunction in the nervous system. Given the similarity of CNTN1 to other Ig-superfamily proteins such as DSCAMs, we also characterized the expression and localization of Cntn1 in the retinas of mutant mice for developmental defects. Despite widespread expression, no anomalies in retinal anatomy were detected histologically or using a battery of cell-type specific antibodies. We therefore conclude that the phenotype of the Cntn1 mice arises from dysfunction in the brain, spinal cord or peripheral nervous system, and is similar in either a BALB/c or B6;129;Black Swiss background, raising a possible discordance between the mouse and human phenotypes resulting from Cntn1 mutations