[Show abstract][Hide abstract] ABSTRACT: The potential contribution of plasmacytoid dendritic cells (pDCs) in the presentation of tumor cell Ags remains unclear, and some controversies exist with regard to the ability of pDCs to phagocytose cell-derived particulate Ags and cross-present them to MHC class I-restricted T lymphocytes. In this study, we show that human pDCs, although inefficient in the internalization of cell membrane fragments by phagocytosis, can efficiently acquire membrane patches and associated molecules from cancer cells of different histotypes. The transfer of membrane patches to pDCs occurred in a very short time and required cell-to-cell contact. Membrane transfer also included intact HLA complexes, and the acquired Ags could be efficiently recognized on pDCs by tumor-specific CD8(+) T cells. Remarkably, pDCs isolated from human colon cancer tissues displayed a strong surface expression of epithelial cell adhesion molecule, indicating that the exchange of exogenous Ags between pDCs and tumor cells also can occur in vivo. These data demonstrate that pDCs are well suited to acquire membrane patches from contiguous tumor cells by a cell-to-cell contact-dependent mechanism that closely resembles "trogocytosis." This phenomenon may allow pDCs to proficiently present tumor cell-derived Ags, despite limited properties of endophagocytosis.
The Journal of Immunology 12/2013; · 5.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The claustrum is a thin layer of gray matter that is at the center of an active scientific debate. Recently, Constrained Spherical Deconvolution (CSD) tractography has proved to be an extraordinary tool allowing to track white matter fibers from cortex to cortical and subcortical targets with subvoxel resolution. The aim of this study was to evaluate claustral connectivity in the human brain. Ten normal brains were analyzed by using the High Angular Resolution Diffusion Imaging CSD-based technique. Tractography revealed 4 groups of white matter fibers connecting the claustrum with the brain cortex: Anterior, posterior, superior, and lateral. The anterior and posterior cortico-claustral tracts connected the claustrum to prefrontal cortex and visual areas. The superior tract linked the claustrum with sensory-motor areas, while the lateral pathway connected the claustrum to the auditory cortex. In addition, we demonstrated a claustral medial pathway connecting the claustrum with the basal ganglia, specifically with caudate nucleus, putamen, and globus pallidus. An interesting and exciting new finding was the demonstration of a bilateral connection between claustrum and contralateral cortical areas and a well-represented interclaustral communication with interconnection bundles interspersed within the bulk of the trunk of the corpus callosum. The physiological and pathophysiological relevance of these findings are discussed.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to analyze three-dimensional images of the arterial supply to the temporomandibular joint.
Ten patients (five men and five women, mean age 36 years) without signs or symptoms of temporomandibular disorders, who underwent contrast-enhanced computed tomographic (CT) scanning with intravenous contrast, were studied. The direct volume rendering technique of CT images was used, and a data set of images to visualize the vasculature of the human temporomandibular joint in three dimensions was created. After elaboration of the data through post-processing, the arterial supply of the temporomandibular joint was studied.
The analysis revealed the superficial temporal artery, the anterior tympanic artery, the deep temporal artery, the auricular posterior artery, the transverse facial artery, the middle meningeal artery, and the maxillary artery with their branches as the main arterial sources for the lateral and medial temporomandibular joint.
The direct volume rendering technique was found to be successful in the assessment of the arterial supply to the temporomandibular joint. The superficial temporal artery and maxillary artery ran along the lateral and medial sides of the condylar neck, suggesting that these arteries are at increased risk during soft-tissue procedures such as an elective arthroplasty of the temporomandibular joint.
Imaging science in dentistry. 03/2013; 43(1):37-44.
[Show abstract][Hide abstract] ABSTRACT: Periodontal disease is characterized by inflammation and bone loss. The balance between inflammatory mediators and their counter-regulatory molecules may be fundamental for determining the outcome of immune pathology of periodontal disease. Cytokines play crucial roles in the maintenance of tissue homeostasis, a process which requires a delicate balance between anabolic and catabolic activities. In particular, two families of growth factors-such as transforming growth factor-ÃŸl (TGF- ÃŸl) and vascular endothelial growth factor (VEGF) are thought to play important roles in modulating the proliferation and/or migration of structural cells involved in inflammation and regulation of immune responses. The aim of this work was to analyze gingival samples and periodontal tissue specimens collected from thirty-eight patients with chronic periodontal disease and from forty healthy individuals, in order to detect the expression and distribution of TGF-ÃŸl and VEGF between the two groups. TGF-ÃŸl and VEGF expression levels were detected using immunohistochemical analysis and computer-assisted morphometric analysis. The findings presented here suggest that biomarker such as TGF-ÃŸl and VEGF have an important regulating role in the orchestration of the immune response, which in turn influence the outcome of disease establishment and evolution.
[Show abstract][Hide abstract] ABSTRACT: The sarcoglycan (SG) complex (SGC) is a subcomplex within the dystrophin-glycoprotein complex (DGC) and is composed of several transmembrane proteins (α, β, δ, γ, ε and ζ). The DGC supplies a transmembranous connection between the subsarcolemmal cytoskeleton networks and the basal lamina in order to protect the lipid bilayer and to provide a scaffold for signaling molecules in all muscle cells. In addition to its role in muscle tissue, dystrophin and some DGC components are expressed in neurons and glia. Very little is known about the SG subunits in the central nervous system (CNS) and some data suggested the presence of ε and ζ subunits only. In fact, mutations in the ε-SG gene cause myoclonus-dystonia, indicating its importance for brain function. To determine the presence and localization of SGC in the human cerebral cortex, we performed an investigation using immunofluorescence, immunoblotting and reverse transcriptase polymerase chain reaction. The results showed that all SG subunits are expressed in the human cerebral cortex, particularly in large neurons but also in astrocytes. These data suggest that the SG subcomplex may be involved in the organization of CNS synapses.
[Show abstract][Hide abstract] ABSTRACT: Periodontal disease is characterized by inflammation and bone loss. The balance between inflammatory mediators and their counter-regulatory molecules may be fundamental for determining the outcome of the immune pathology of periodontal disease. Transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) represent a family of polypeptide proteins involved in the inflammation and regulation of immune responses, especially in rheumatic disease. The relationship between these growth factors and periodontitis has resulted in a new field of osteoimmunology and provides a context for better understanding the pathogenesis of periodontal disease. Therefore, the aim of this study was to compare the protein expression profile of these inflammatory mediators in 90 patients divided in three groups: healthy control, chronic periodontitis and in rheumatic disease, scleroderma. The findings presented here highlight that biomarkers, such as TGF-β1 and VEGF, play a key role in the evolution of the immune response, which in turn influences the outcome of disease establishment.
International Journal of Molecular Medicine 06/2012; 30(3):502-8. · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Integrins are heterodimeric cell surface membrane proteins linking the extracellular matrix to actin. α7B integrin is detected in proliferating and adult myofibers, whereas α7A plays a role in regenerating muscle fibers with a minor function in mature muscle fibers. The expression levels of β1A appear to be very low, whereas β1D appears to be the predominant integrin form in mature muscle. Considering the important features of masseter muscle we have studied integrin expression in masseter muscle specimens of surgical patients with posterior right crossbite and comparing them to left side masseter muscle specimens. Our results showed that the expression of integrins was significantly lower in the crossbite side muscle. Furthermore, the most important finding is that β1A is clearly detectable in adult masseter muscle. This behavior could be due to the particular composition of masseter, since it contains hybrid fibers showing the capacity to modify the contractile properties to optimize the energy efficiency or the action of the muscle during contraction. Moreover, masseter is characterized by a high turnover of muscle fibers producing a regeneration process. This may indicate a longer time to heal, justifying the loss of β1D and the consequential increase of β1A. Thus, our data provide the first suggestion that integrins in masseter muscle play a key role regulating the functional activity of muscle and allowing the optimization of contractile forces.
International Journal of Molecular Medicine 04/2012; 30(2):235-42. · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Costameres encircle the myocyte perpendicular to its long axis, and comprise two protein complexes: the dystrophin-glycoprotein complex (DGC) and the vinculin-talin-integrin system. They participate in signaling functions and protect muscle cells from damage induced by workload. The behaviour of those proteins has been a focus of study starting from skeletal and smooth muscle cells to cardiomyocytes, and still represents a topical subject for cardiovascular translational research. This review summarizes the past and present novel approaches of our and other groups of work on this subject of research.
Annales de cardiologie et d'angeiologie 02/2012; 61(1):55-60. · 0.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ureteropelvic junction obstruction is one of the most common causes of hydronephrosis in children. A malfunction of smooth muscle cells is believed to be the underlying mechanism causing obstruction. We investigated the expression of some integrins, talin and β-dystroglycan, considered the main compound of smooth muscle cell cytoskeleton, and active caspase 3 at the level of the ureteropelvic junction obstruction.
Specimens were obtained at pyeloplasty in 12 children with ureteropelvic junction obstruction. Six control specimens were obtained during organ explantation. Specimens were divided into renal pelvis, ureteropelvic junction and ureter below the obstruction. Western blot analysis of active caspase 3, and immunofluorescence and polymerase chain reaction analysis were performed for α7A, β1A, α7B and β1D integrins, talin and β-dystroglycan.
Talin and β-dystroglycan were slightly impaired in ureteropelvic junction obstruction, while α7B and β1D integrins were severely reduced, and α7A, β1A and active caspase 3 were significantly enhanced compared to controls.
We demonstrated activation of apoptosis and a critical alteration of cytoskeleton that might explain the altered function and the increased apoptosis in smooth muscle cells in ureteropelvic junction obstruction. The delayed rearrangement of the cytoskeleton of smooth muscle cells in ureteropelvic junction obstruction might be linked to a postnatal splicing from α7A and β1A to α7B and β1D integrins, respectively. This relationship could explain the common clinical scenario of spontaneous improvement of hydronephrosis in children with suspected ureteropelvic junction obstruction.
The Journal of urology 06/2011; 185(6):2314-9. · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The carotid labyrinth is an enigmatic endocrine structure of unknown chemosensory function lying in the gill region of the catfishes. The carotid body is found at the carotid bifurcation of amphibians and all mammalian vertebrates on the evolutionary tree. It is a vascular expansion comprised of a cluster of glomus cells with associated (afferent and efferent) innervations. In the catfish species studied (Clarias batrachus) a neurosecretory cell system consisting of pseudobranchial neurosecretory cells connect the carotid labyrinth or large vessels (both the efferent branchial artery and dorsal aorta), and is likely akin to the glomus cells, but comparing these structures in widely divergent vertebrate species, the conclusion is that the structural components are more elaborate than those of terrestrial vertebrates. However, these cells reveal both an endocrine phenotype (such as the association with capillaries and large vessels) and the presence of regulatory substances such as neurotransmitters and neuropeptides producing good evidence for high levels of conservation of these substances that are present in the glomus cells of mammalian vertebrates. VIP-immunopositive neuronal cell bodies are detected in the periphery of the carotid labyrinth. They are presumptive local neurons that differ from pseudobranchial neurosecretory cells, the latter failing to express VIP in their soma.
[Show abstract][Hide abstract] ABSTRACT: The goal of this report was to highlight lateral ventricle morphology and volume differences between schizophrenia patients and matched controls. Subjects identified as suitable for analysis comprised 15 schizophrenia patients and 15 healthy subjects. The method applied is three-dimensional (3D) volume rendering starting from structural magnetic resonance imaging (MRI) studies of selected ventricular regions. Differences between groups relative to the global ventricular system and its subdivisions were found. Total lateral ventricle volume, right ventricle volume and left ventricle volume were all higher in schizophrenia patients than in controls; unilateral differences between the two groups were also outlined (right ventricle volume>left ventricle volume in schizophrenia patients vs. healthy subjects). Furthermore, occipital and frontal horn enlargement was found in schizophrenia patients compared with normal controls, but the difference in the temporal horn was not statistically significant. A substantial difference was noted in lateral ventricle morphology between the two groups. Our findings were consistent with the literature and may shed light on some of the discrepancies in previous reports on differences in lateral ventricle volume enlargement.
Psychiatry Research 07/2010; 183(1):52-8. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteonecrosis of the jaw (ONJ) is an adverse outcome associated to bisphosphonate treatment. However, it is not known whether the ONJ lesion originates in the bone, or whether it may initiate in the oral mucosa. The aim of our study was to evaluate the pattern of basal lamina of oral mucosa after bisphosphonate administration and to analyze the structural damage of the mucosa in ONJ patients, and in subjects treated with bisphosphonates without osteonecrosis. By immunohistochemistry, we evaluated changes in basement membrane by expression of signalling proteins, laminin, and type IV collagen. All tested proteins were almost absent in basal lamina and mucosa of subjects treated with bisphosphonates without osteonecrosis, whereas in mucosa of patients with ONJ, they showed a clearly detectable pattern of the same proteins, specifically in basal lamina, but less in comparison to control samples. Moreover, in pathological mucosa, the clearly detectable staining pattern for VEGF indicated a massive neoangiogenesis. Bisphosphonates induce changes in expression of proteins also in oral mucosa. The increase of these proteins in basal lamina, and the neo-angiogenesis, concomitant with formation of the lesion, could indicate a compensative behaviour in the remodelling of the gingival mucosa in order to restore the epithelial architecture.
[Show abstract][Hide abstract] ABSTRACT: This study evaluated the activation of different cortical areas during nondeliberate chewing of soft and hard boluses in five right-handed and five left-handed subjects with normal occlusion, to determine different hemispheric prevalences. The study was conducted with a functional Magnetic Resonance Imaging (1.5 T Magnetom Vision - Siemens Medical, Germany) using a head coil. The results showed that the most frequently activated areas were Brodmann's areas four and six in the primary motor and premotor cortex, the insula and Broca's area and, overall, showed greater activity of the cortical mastication area (CMA) in the right hemisphere for right-handed and in the left hemisphere for left-handed subjects.
Cranio: the journal of craniomandibular practice 04/2010; 28(2):114-21. · 1.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hirschsprung's disease (HD) is a development disorder of the enteric nervous system in which the altered innervation explains the inability of the aganglionic segment to relax. Impairment of cytoskeleton in SMC of aganglionic bowel has been shown. Sarcoglycan subcomplex (SG) may support the development and maintenance of muscle cells. We examined the SG subunit expression in colonic aganglionic and ganglionic specimens obtained from patients with HD. Full-thickness bowel specimens were obtained from six patients with HD. Six normal colon specimens were used as controls. Immunofluorescent analysis and reverse transcriptase polymerase chain reaction evaluation were performed for alpha-, beta-, gamma-, delta- and epsilon-SG. In control colon, the indirect immunofluorescence showed a strong staining pattern of beta- gamma- delta- and epsilon-SG while a weak positivity of alpha-SG was recorded. In aganglionic bowel, immunofluorescence intensity values documented a significant lack of epsilon-SG while an enhanced alpha-SG, coupled to a loss of epsilon-SG, was recorded in ganglionic bowel in HD-affected patients. Our observations underscore the assumption that non-neuronal elements of the colon might play a key role in the pathogenesis of HD and loss of epsilon-SG might critically alter the cytoskeleton in the aganglionic bowel segment. Up-regulation of alpha-SG is probably an acquired phenomenon to reinforce the sarcolemma and to perform a forceful contraction in dilated ganglionic HD-affected colon, related to chronic pseudo-obstruction, contributing to the intestinal dysmotility that persists in 20% of patients after resection of the aganglionic bowel.
International Journal of Molecular Medicine 03/2010; 25(3):353-9. · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The sarcoglycan complex is a multimember transmembrane complex interacting with other proteins to provide a mechano-signaling connection from the cytoskeleton to the extracellular matrix in myofibers. This complex plays a key role at the membrane and is crucial in maintaining sarcolemma viability in muscle fibers. Recent observations have demonstrated that in the lung this glycoprotein is associated with both alveoli and bronchioles, and that the urogenital and digestive tracts are epsilon-sarcoglycan positive. Further addressing this issue, in this work we extend our previous studies to better verify whether the sarcoglycan complex also exists in epithelial tissue. All our observations showed staining for all sarcoglycans to be a normal pattern in all tested epithelial cells. We hypothesize a key role for sarcoglycans in bidirectional signaling between cells and extracellular matrix, and an important role in the regulation of inhibitory synapses and of blood brain barrier.
Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia 01/2010; 115(1-2):19-24.
[Show abstract][Hide abstract] ABSTRACT: To describe representative Western philosophical, theological, and scientific ideas regarding the nature and location of the soul from the Egyptians to the contemporary period; and to determine the principal themes that have structured the history of the development of the concept of the soul and the implications of the concept of the soul for medical theory and practice.
We surveyed the ancient Egyptian, Greek, and Roman periods, the early, Medieval, and late Christian eras, as well as the Renaissance, Enlightenment, and Modern periods to determine the most salient ideas regarding the nature and location of the soul.
In the history of Western theological, philosophical, and scientific/medical thought, there exist 2 dominant and, in many respects, incompatible concepts of the soul: one that understands the soul to be spiritual and immortal, and another that understands the soul to be material and mortal. In both cases, the soul has been described as being located in a specific organ or anatomic structure or as pan-corporeal, pervading the entire body, and, in some instances, trans-human and even pan-cosmological. Moreover, efforts to discern the nature and location of the soul have, throughout Western history, stimulated physiological exploration as well as theoretical understanding of human anatomy. The search for the soul has, in other words, led to a deepening of our scientific knowledge regarding the physiological and, in particular, cardiovascular and neurological nature of human beings. In addition, in virtually every period, the concept of the soul has shaped how societies thought about, evaluated, and understood the moral legitimacy of scientific and medical procedures: from performing abortions and autopsies to engaging in stem cell research and genetic engineering.
Our work enriches our shared understanding of the soul by describing some of the key formulations regarding the nature and location of the soul by philosophers, theologians, and physicians. In doing so, we are better able to appreciate the significant role that the concept of the soul has played in the development of Western scientific, medical, and spiritual life. Although ideas about the soul have changed significantly throughout Western history, the idea of the soul as being real and essential to one's personhood has been, and remains, pervasive throughout every period of Western history.
[Show abstract][Hide abstract] ABSTRACT: We have applied high-quality medical imaging techniques to study the structure of the human ankle. Direct volume rendering, using specific algorithms, transforms conventional two-dimensional (2D) magnetic resonance image (MRI) series into 3D volume datasets. This tool allows high-definition visualization of single or multiple structures for diagnostic, research, and teaching purposes. No other image reformatting technique so accurately highlights each anatomic relationship and preserves soft tissue definition. Here, we used this method to study the structure of the human ankle to analyze tendon-bone-muscle relationships. We compared ankle MRI and computerized tomography (CT) images from 17 healthy volunteers, aged 18-30 years (mean 23 years). An additional subject had a partial rupture of the Achilles tendon. The MRI images demonstrated superiority in overall quality of detail compared to the CT images. The MRI series accurately rendered soft tissue and bone in simultaneous image acquisition, whereas CT required several window-reformatting algorithms, with loss of image data quality. We obtained high-quality digital images of the human ankle that were sufficiently accurate for surgical and clinical intervention planning, as well as for teaching human anatomy. Our approach demonstrates that complex anatomical structures such as the ankle, which is rich in articular facets and ligaments, can be easily studied non-invasively using MRI data.
Journal of Anatomy 09/2009; 215(5):592-9. · 2.36 Impact Factor