Laminin receptors in the retina: sequence analysis of the chick integrin alpha 6 subunit. Evidence for transcriptional and posttranslational regulation.

The integrin alpha 6 beta 1 is a prominent laminin receptor used by many cell types. In the present work, we isolate clones and determine the primary sequence of the chick integrin alpha 6 subunit. We show that alpha 6 beta 1 is a prominent integrin expressed by cells in the developing chick retina. Between embryonic days 6 and 12, both retinal ganglion cells and other retinal neurons lose selected integrin functions, including the ability to attach and extend neurites on laminin. In retinal ganglion cells, we show that this is correlated with a dramatic decrease in alpha 6 mRNA and protein, suggesting that changes in gene expression account for the developmental regulation of the interactions of these neurons with laminin. In other retinal neurons the expression of alpha 6 mRNA and protein remains high while function is lost, suggesting that the function of the alpha 6 beta 1 heterodimer in these cells is regulated by posttranslational mechanisms

Epithelial integrin alpha 6 beta 4: complete primary structure of alpha 6 and variant forms of beta 4.

The integrin alpha 6 beta 4 is a heterodimer predominantly expressed by epithelia. While no definite receptor function has yet been assigned to it, this integrin may mediate adhesive and/or migratory functions of epithelial cells. We have determined the complete primary structure of both the alpha 6 and beta 4 subunits from cDNA clones isolated from pancreatic carcinoma cell line libraries. The deduced amino acid sequence of alpha 6 is homologous to other integrin alpha chains (18-26% identity). Antibodies to an alpha 6 carboxy terminus peptide immunoprecipitated alpha 6 beta 4 complexes from carcinoma cells and alpha 6 beta 1 complexes from platelets, providing further evidence for the association of alpha 6 with more than one beta subunit. The deduced amino acid sequence of beta 4 predicts an extracellular portion homologous to other integrin beta chains, and a unique cytoplasmic domain comprised of greater than 1,000 residues. This agrees with the structures of the beta 4 cDNAs from normal epithelial cells (Suzuki, S., and Y. Naitoh. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:757-763; Hogervost, F., I. Kuikman, A. E. G. Kr. von dem Borne, and A. Sonnenberg. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:765-770). Compared to these structures, however, the beta 4 cDNAs that we have cloned from carcinoma cells contain extra sequences. One of these is located in the 5'-untranslated region, and may encode regulatory sequences. Another specifies a segment of 70 amino acids in the cytoplasmic tail. Amplification by reverse transcription-polymerase chain reaction of mRNA indicated that multiple forms of beta 4 may exist, possibly due to cell-type specific alternative splicing. The unique structure of beta 4 suggests its involvement in novel cytoskeletal interactions. Consistent with this possibility, alpha 6 beta 4 is mostly concentrated on the basal surface of epithelial cells, but does not colocalize with components of adhesion plaques

Olfactory dysfunction in patients with chronic rhinosinusitis with nasal polyps is associated with clinical-cytological grading severity

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder, affecting about 4% of the worldwide population and strongly impacting the quality of life. CRSwNP is still a challenge for ENT specialists in terms of its unknown pathogenesis, difficulty in management and frequent relapse. Olfactory impairment frequently affects CRSwNP patients. We tested the hypothesis that clinical-cytological grading (CCG) could be associated with olfactory dysfunction. The study was cross-sectional, enrolling 62 patients (37 males, 25 females, mean age 49 years, range 18-83) suffering from newly diagnosed CRSwNP. Olfactory dysfunction was very frequent (about 90%) and did not depend on nasal obstruction as assessed by both polyp size and nasal airflow limitation. A CCG > 4 was the best cutoff value to suspect olfactory dysfunction [area under the ROC curve of 0.831 (0.715 to 0.914)]; in addition, the statistical risk of having dysosmia was over 7-fold higher in subjects with CCG > 4 compared with subjects reporting a CCG < 4 (adjOR 7.46). The present study underlines that olfactory dysfunction is common in CRSwNP patients and demonstrates an association between olfactory dysfunction and inflammation, suggesting that CCG could be useful in the work-up of CRSwNP patients and in suspecting olfactory impairment

Expression and function of alpha(v)beta(3) and alpha(v)beta(5) integrins in the developing pancreas: roles in the adhesion and migration of putative endocrine progenitor cells.

Cell-cell and cell-matrix interactions play a critical role in tissue morphogenesis and in homeostasis of adult tissues. The integrin family of adhesion receptors regulates cellular interactions with the extracellular matrix, which provides three-dimensional information for tissue organization. It is currently thought that pancreatic islet cells develop from undifferentiated progenitors residing within the ductal epithelium of the fetal pancreas. This process involves cell budding from the duct, migration into the surrounding mesenchyme, differentiation, and clustering into the highly organized islet of Langerhans. Here we report that alpha(v)beta(3) and alpha(v)beta(5), two integrins known to coordinate epithelial cell adhesion and movement, are expressed in pancreatic ductal cells and clusters of undifferentiated cells emerging from the ductal epithelium. We show that expression and function of alpha(v)beta(3) and alpha(v)beta(5) integrins are developmentally regulated during pancreatic islet ontogeny, and mediate adhesion and migration of putative endocrine progenitor cells both in vitro and in vivo in a model of pancreatic islet development. Moreover, we demonstrate the expression of fibronectin and collagen IV in the basal membrane of pancreatic ducts and of cell clusters budding from the ductal epithelium. Conversely, expression of vitronectin marks a population of epithelial cells adjacent to, or emerging from, pancreatic ducts. Thus, these data provide the first evidence for the contribution of integrins alpha(v)beta(3) and alpha(v)beta(5) and their ligands to morphogenetic events in the human endocrine pancreas

Defining signal thresholds in DNA microarrays: exemplary application for invasive cancer

BACKGROUND: Genome-wide or application-targeted microarrays containing a subset of genes of interest have become widely used as a research tool with the prospect of diagnostic application. Intrinsic variability of microarray measurements poses a major problem in defining signal thresholds for absent/present or differentially expressed genes. Most strategies have used fold-change threshold values, but variability at low signal intensities may invalidate this approach and it does not provide information about false-positives and false negatives. RESULTS: We introduce a method to filter false-positives and false-negatives from DNA microarray experiments. This is achieved by evaluating a set of positive and negative controls by receiver operating characteristic (ROC) analysis. As an advantage of this approach, users may define thresholds on the basis of sensitivity and specificity considerations. The area under the ROC curve allows quality control of microarray hybridizations. This method has been applied to custom made microarrays developed for the analysis of invasive melanoma derived tumor cells. It demonstrated that ROC analysis yields a threshold with reduced missclassified genes in microarray experiments. CONCLUSIONS: Provided that a set of appropriate positive and negative controls is included on the microarray, ROC analysis obviates the inherent problem of arbitrarily selecting threshold levels in microarray experiments. The proposed method is applicable to both custom made and commercially available DNA microarrays and will help to improve the reliability of predictions from DNA microarray experiments

The emerging role of cold atmospheric plasma in implantology: A review of the literature

In recent years, cold atmospheric plasma (CAP) technologies have received increasing attention in the field of biomedical applications. The aim of this article is to review the currently available literature to provide an overview of the scientific principles of CAP application, its features, functions, and its applications in systemic and oral diseases, with a specific focus on its potential in implantology. In this narrative review, PubMed, Medline, and Scopus databases were searched using key words like “cold atmospheric plasma”, “argon plasma”, “helium plasma”, “air plasma”, “dental implants”, “implantology”, “peri‐implantitis”, “decontamination”. In vitro studies demonstrated CAP’s potential to enhance surface colonization and osteoblast activity and to accelerate mineralization, as well as to determine a clean surface with cell growth comparable to the sterile control on both titanium and zirconia surfaces. The effect of CAP on biofilm removal was revealed in comparative studies to the currently available decontamination modalities (laser, air abrasion, and chlorhexidine). The combination of mechanical treatments and CAP resulted in synergistic antimicrobial effects and surface improvement, indicating that it may play a central role in surface “rejuvenation” and offer a novel approach for the treatment of peri‐implantitis. It is noteworthy that the CAP conditioning of implant surfaces leads to an improvement in osseointegration in in vivo animal studies. To the best of our knowledge, this is the first review of the literature providing a summary of the current state of the art of this emerging field in implantology and it could represent a point of reference for basic researchers and clinicians interested in approaching and testing new technologies

New laboratory predictive tools in deep neck space infections

Introduction. Deep neck space infections (DNSIs) are a group of infective suppurative dis-eases involving deep neck spaces and cervical fascia. Necrotising and septic evolutions are rare, but severe complications can dramatically affect the prognosis and should be promptly managed. Clinical examination often has low sensitivity, although instrumental diagnosis may delay te treatment. We investigated two laboratory tools, LRINEC (Laboratory Risk Indicator for the Necrotizing fasciitis) and NLR (neutrophil to lymphocyte ratio), in the expectation to find a rapidly available predictive indicator that may help in distinguishing necrotising complications and/or systemic septic involvement. Methods. A retrospective observational cohort study was performed on 118 patients who had underwent surgical treatment for DNSIs at our Surgical Unit. LRINEC, NLR and the product LRINEC x NLR were calculated. Results. Statistical analysis showed that these scores may have utility in rapidly predicting the risk of necrotising fasciitis and systemic involvement at an early diagnostic stage. Conclusions. Further studies with a larger cohort may be necessary in order to increase the sensitivity and specificity

Randomised study for the 1-year crestal bone maintenance around modified diameter implants with different loading protocols: a radiographic evaluation.

This study evaluated by standardised digitised periapical radiography the crestal bone maintenance around modified diameter internal hex implants with variable thread design and narrow neck loaded with different procedures. Forty implants were placed in 25 patients. Twenty implants were conventionally loaded, 20 ones immediately loaded. Radiographs were taken with a customised bite record and processed with software. Measurements of bone from the fixture–abutment junction to mesial and distal marginal bone levels were made. Student’s t test statistical analysis was adopted. Baseline data were variable; at 1-year follow-up, there were no significant differences for marginal bone loss between immediately and conventionally loaded maxillary implants (p=0.1031), whilst there were slight significant differences between immediately and conventionally loaded implants in the mandible (p=0.0141). Crestal bone maintenance around conventionally and immediately loaded modified diameter implants was similar, with slight significant differences in mandible where a lower marginal bone loss was observed

Muon Capture on the Proton and Deuteron

By measuring the lifetime of the negative muon in pure protium (hydrogen-1), the MuCap experiment determines the rate of muon capture on the proton, from which the proton's pseudoscalar coupling g_p may be inferred. A precision of 15% for g_p has been published; this is a step along the way to a goal of 7%. This coupling can be calculated precisely from heavy baryon chiral perturbation theory and therefore permits a test of QCD's chiral symmetry. Meanwhile, the MuSun experiment is in its final design stage; it will measure the rate of muon capture on the deuteron using a similar technique. This process can be related through pionless effective field theory and chiral perturbation theory to other two-nucleon reactions of astrophysical interest, including proton-proton fusion and deuteron breakup.Comment: Submitted to the proceedings of the 2007 Advanced Studies Institute on Symmetries and Spin (SPIN-Praha-2007