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1.
Methods Mol Biol ; 2206: 67-88, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32754812

RESUMO

Several studies are available addressing the mechanisms of vascular morphogenesis in order to unravel how cooperative cell behavior can follow from the underlying, genetically regulated behavior of endothelial cells and from cell-to-cell and cell-to-extracellular matrix interactions. From the morphological standpoint several aspects of the process are of interest. They include the way the pattern of vessels fills the available tissue space and how the network grows during the angiogenic process, namely how a main trunk divides into smaller branches, and how branching occurs at different distances from the root point of a vascular tree. A third morphological aspect of interest concerns the spatial relationship between vessels and tissue cells able to secrete factors modulating endothelial cells self-organization, thus influencing vascular rearrangement.In the present chapter image analysis methods allowing for a quantitative characterization of these morphological aspects will be detailed and discussed. They are almost based on concepts derived from the theoretical framework represented by spatial statistics.

2.
Int J Mol Sci ; 21(19)2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33019660

RESUMO

The carotid body may undergo plasticity changes during development/ageing and in response to environmental (hypoxia and hyperoxia), metabolic, and inflammatory stimuli. The different cell types of the carotid body express a wide series of growth factors and corresponding receptors, which play a role in the modulation of carotid body function and plasticity. In particular, type I cells express nerve growth factor, brain-derived neurotrophic factor, neurotrophin 3, glial cell line-derived neurotrophic factor, ciliary neurotrophic factor, insulin-like-growth factor-I and -II, basic fibroblast growth factor, epidermal growth factor, transforming growth factor-α and -ß, interleukin-1ß and -6, tumor necrosis factor-α, vascular endothelial growth factor, and endothelin-1. Many specific growth factor receptors have been identified in type I cells, indicating autocrine/paracrine effects. Type II cells may also produce growth factors and express corresponding receptors. Future research will have to consider growth factors in further experimental models of cardiovascular, metabolic, and inflammatory diseases and in human (normal and pathologic) samples. From a methodological point of view, microarray and/or proteomic approaches would permit contemporary analyses of large groups of growth factors. The eventual identification of physical interactions between receptors of different growth factors and/or neuromodulators could also add insights regarding functional interactions between different trophic mechanisms.

3.
Surg Radiol Anat ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32940718

RESUMO

INTRODUCTION: Anatomy has traditionally been taught via dissection and didactic lectures. The rising prevalence of informatics plays an increasingly important role in medical education. It is hypothesized that virtual dissection can express added value to the traditional one. METHODS: Second-year medical students were randomised to study anatomical structures by virtual dissection (intervention) or textbooks (controls), according to the CONSORT guidelines. Subsequently, they applied to the corresponding gross dissection, with a final test on their anatomical knowledge. Univariate analysis and multivariable binary logistic regression were performed. RESULTS: The rate of completed tests was 76.7%. Better overall test performance was detected for the group that applied to the virtual dissection (OR 3.75 with 95% CI 0.91-15.49; p = 0.06). A comparable performance between groups in basic anatomical knowledge (p 0.45 to 0.92) but not muscles and 2D-3D reporting of anatomical structures was found, for which the virtual dissection was of tendential benefit (p 0.08 to 0.13). Medical students who applied to the virtual dissection were over three times more likely to report a positive outcome at the post-dissection test than those who applied to textbooks of topographical anatomy. This would be of benefit with particular reference to the understanding of 2D-3D spatial relationships between anatomical structures. CONCLUSION: The combination of virtual to traditional gross dissection resulted in a significant improvement of second-year medical students' learning outcomes. It could be of help in maximizing the impact of practical dissection, overcoming the contraction of economic resources, and the shortage of available bodies.

4.
Prog Mol Biol Transl Sci ; 169: 247-277, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31952688

RESUMO

The discovery of receptor-receptor interactions in the early 1980s, together with a more accurate focusing of allosteric mechanisms in proteins, expanded the knowledge on the G protein-coupled receptor (GPCR)-mediated signaling processes. GPCRs were seen to operate not only as monomers, but also as quaternary structures shaped by allosteric interactions. These integrative mechanisms can change the function of the GPCRs involved, leading to a sophisticated dynamic of the receptor assembly in terms of modulation of recognition and signaling. In this context, the heterodimeric complex formed by the adenosine A2A and the dopamine D2 receptors likely represents a prototypical example. The pharmacological evidence obtained, together with the tissue distribution of the A2A-D2 heteromeric complexes, suggested they could represent a target for new therapeutic strategies addressing significant disorders of the central nervous system. The research findings and the perspectives they offer from the therapeutic standpoint are the focus of the here presented discussion.

5.
Microvasc Res ; 128: 103935, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31655306

RESUMO

The chick embryo includes the area vasculosa is subdivided into 2 concentric zones, the inner transparent area pellucida vasculosa and the surrounding less transparent area opaca vasculosa, peripherally limited by the sinus terminalis. In this study, we have analyzed by a modern morphometric approach the total length of the vascular network, the number of vascular branches, of the branching points density, the modality of vessel ramification, and spatial arrangement of the vascular network in four consecutive stages of development of the area vasculosa. The results have shown that there is a significant 15% increase in the total length of the vascular network associated with a progressive increase of the number of vascular branches and of the branching points density. Moreover, the results indicated that vascular spatial disorder significantly decreased during development in area vasculosa, suggesting a more uniform occupancy of the tissue by the vascular pattern. Finally, a more regular pattern of branching was observed, as indicated by the significant decrease of topological disorder of the vascular tree.

6.
J Anat ; 235(1): 80-87, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30945285

RESUMO

The infrapatellar fat pad (IFP) is an intracapsular but extrasynovial structure, located between the patellar tendon, the femoral condyles and the tibial plateau. It consists of white adipose tissue, organised in lobules defined by thin connective septa. The aim of this study is the morphometric and ultrasonographic analysis of IFP in subjects without knee pathology during flexion-extension movements. The morphometric study was conducted on 20 cadavers (15M, 5F, mean age 80.2 years). Ultrasound was performed on 24 volunteers with no history of knee diseases (5M, 19F, mean age: 45 years). The characteristics of the adipose lobules near the patellar tendon and in the deep portion of the IFP were evaluated. Numerical models were provided, according to the size of the lobules. At histological examination, the adipose lobules located near the patellar tendon were larger (mean area 12.2 mm2  ± 5.3) than those at a deeper level (mean area 1.34 mm2  ± 0.7, P < 0.001) and the thickness of the septa of the deepest adipose lobules (mean value 0.35 mm ± 0.32) was greater than that of the superficial one (mean value 0.29 mm ± 0.25, P < 0.001). At ultrasound, the IFP was seen to be composed of very large lobules in the superficial part (mean area 0.29 cm2  ± 0.17 in extension), with a significant reduction in flexion (mean area 0.12 cm2  ± 0.07, P < 0.01). The deep lobules were smaller (mean area 0.11 cm2  ± 0.08 in extension) and did not change their values (mean area 0.19 cm2  ± 0.52 in flexion, P > 0.05). In the sagittal plane, the reduction of thickness of the superficial layer (with large adipose lobules) during flexion was 20.6%, whereas that of the deep layer (with small adipose lobules) was 1.3%. Numerical simulation of vertical loads, corresponding to flexion of the knee, showed that stress mainly developed within the interlobular septa and opposed bulging of the lobules. The characteristics of the lobular arrangement of the IFP (large lobules with superficial septa in the superficial part and small lobules with thick septa in the deep one), significant changes in the areas and perimeters of the superficial lobules, and the reduced thickness of the superficial layer during flexion all indicate the dynamic role played by the IFP in knee kinematics.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30833931

RESUMO

The discovery of receptor-receptor interactions (RRI) has expanded our understanding of the role that G protein-coupled receptors (GPCRs) play in intercellular communication. The finding that GPCRs can operate as receptor complexes, and not only as monomers, suggests that several different incoming signals could already be integrated at the plasma membrane level via direct allosteric interactions between the protomers that form the complex. Most research in this field has focused on neuronal populations and has led to the identification of a large number of RRI. However, RRI have been seen to occur not only in neurons but also in astrocytes and, outside the central nervous system, in cells of the cardiovascular and endocrine systems and in cancer cells. Furthermore, RRI involving the formation of macromolecular complexes are not limited to GPCRs, being also observed in other families of receptors. Thus, RRI appear as a widespread phenomenon and oligomerization as a common mechanism for receptor function and regulation. The discovery of these macromolecular assemblies may well have a major impact on pharmacology. Indeed, the formation of receptor complexes significantly broadens the spectrum of mechanisms available to receptors for recognition and signaling, which may be implemented through modulation of the binding sites of the adjacent protomers and of their signal transduction features. In this context, the possible appearance of novel allosteric sites in the receptor complex structure may be of particular relevance. Thus, the existence of RRI offers the possibility of new therapeutic approaches, and novel pharmacological strategies for disease treatment have already been proposed. Several challenges, however, remain. These include the accurate characterization of the role that the receptor complexes identified so far play in pathological conditions and the development of ligands specific to given receptor complexes, in order to efficiently exploit the pharmacological properties of these complexes.

8.
Int J Dev Neurosci ; 77: 3-17, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30465872

RESUMO

The stunning diversity of neurons and glial cells makes possible the higher functions of the central nervous system (CNS), allowing the organism to sense, interpret and respond appropriately to the external environment. This cellular diversity derives from a single primary progenitor cell type initiating lineage leading to the formation of both differentiated neurons and glial cells. The processes governing the differentiation of the progenitor pool of cells into mature nerve cells will be here briefly reviewed. They involve morphological transformations, specialized modes of cell division, migration, and controlled cell death, and are regulated through cell-cell interactions and cues provided by the extracellular matrix, as well as by humoral factors from the cerebrospinal fluid and the blood system. In this respect, a quite large body of studies have been focused on cytokines, proteins representing the main signaling network that coordinates immune defense and the maintenance of homeostasis. At the same time, they are deeply involved in CNS development as regulatory factors. This dual role in the nervous system appears of particular relevance for CNS pathology, since cytokine dysregulation (occurring as a consequence of maternal infection, exposure to environmental factors or prenatal hypoxia) can profoundly impact on neurodevelopment and likely influence the response of the adult tissue during neuroinflammatory events.


Assuntos
Citocinas/metabolismo , Microglia/metabolismo , Neurogênese/fisiologia , Neurônios/metabolismo , Transdução de Sinais/fisiologia , Animais , Astrócitos/metabolismo , Humanos
9.
Rev Neurosci ; 29(7): 703-726, 2018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-29466243

RESUMO

The proposal of receptor-receptor interactions (RRIs) in the early 1980s broadened the view on the role of G protein-coupled receptors (GPCR) in the dynamics of the intercellular communication. RRIs, indeed, allow GPCR to operate not only as monomers but also as receptor complexes, in which the integration of the incoming signals depends on the number, spatial arrangement, and order of activation of the protomers forming the complex. The main biochemical mechanisms controlling the functional interplay of GPCR in the receptor complexes are direct allosteric interactions between protomer domains. The formation of these macromolecular assemblies has several physiologic implications in terms of the modulation of the signaling pathways and interaction with other membrane proteins. It also impacts on the emerging field of connectomics, as it contributes to set and tune the synaptic strength. Furthermore, recent evidence suggests that the transfer of GPCR and GPCR complexes between cells via the exosome pathway could enable the target cells to recognize/decode transmitters and/or modulators for which they did not express the pertinent receptors. Thus, this process may also open the possibility of a new type of redeployment of neural circuits. The fundamental aspects of GPCR complex formation and function are the focus of the present review article.


Assuntos
Comunicação Celular/fisiologia , Modelos Moleculares , Multimerização Proteica , Receptores Acoplados a Proteínas-G/metabolismo , Animais , Humanos , Simulação de Dinâmica Molecular , Receptores Acoplados a Proteínas-G/química
10.
Microsurgery ; 38(1): 76-84, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28767166

RESUMO

BACKGROUND: The superior (SGA) and the inferior gluteal artery (IGA) perforator flaps are widely used in pressure-sore repair and in breast reconstruction. The aim was to exhaustively depict the topographical anatomy of the whole system of perforators in the buttock. METHODS: Eighty lower-extremity computed tomographic angiography (CTA) of patients (20 males/20 females, mean age 61-years old, range 38-81) were considered. The source artery, location, type, and caliber of gluteal perforators were analyzed. The location of perforators was reproduced using a standardized two-dimensional grid on the coronal plane, centered onto defined bone landmarks. We defined "radiosome" the cutaneous vascular territory of a source artery inferred through the representation of its whole perforator system at the exit point through the deep fascia. RESULTS: A mean number of 25.6 ± 5.7 perforators in the gluteal region was observed, distributed as follows: 11.6 ± 4.8(45.2%) from SGA; 7.9 ± 4.5(30.8%) from IGA; 1.5 ± 0.8(5.8%) from fifth lumbar artery; 1.2 ± 0.8(4.7%) from internal pudendal artery; 1.2 ± 1(4.8%) from lateral circumflex femoral artery; 0.3 ± 0.7(1.2%) from circumflex iliac superficial artery. At least one large (internal diameter > 1 mm) SGA septocutaneous perforator was present in 77.5% of patients. CONCLUSIONS: The gluteal region is vascularized by perforators of multiple source arteries. Septocutaneous perforators of SGA and IGA were planned along a curve drawn from the posterior-superior border of the iliac crest to the greater trochanter. The lumbar artery perforators are clustered over the apex of the iliac crest; the internal pudendal artery perforators are clustered medially to the ischiatic tuberosity. Contributions can also come from the sacral and superficial circumflex iliac arteries.


Assuntos
Nádegas/irrigação sanguínea , Angiografia por Tomografia Computadorizada , Retalho Perfurante/irrigação sanguínea , Adulto , Idoso , Idoso de 80 Anos ou mais , Pontos de Referência Anatômicos , Nádegas/diagnóstico por imagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Exp Cell Res ; 359(1): 179-184, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28756894

RESUMO

Macrophages and mast cells are usually present in the tumor microenvironment and play an important role as regulators of inflammation, immunological response and angiogenesis in the tumor microenvironment. In this study, we have evaluated macrophage, mast cell, and microvessel density in a selected group of different grade of invasive breast carcinoma tumor specimens. Furthermore, we have investigated the pattern of distribution of CD68-positive macrophages and tryptase-positive mast cells around tumor glands. Results have shown that: A) Macrophages are more numerous in G2 and G3 breast cancer stages respect to controls, the per cent of macrophages in G1 samples was comparable to the controls, and the spatial relationship between macrophages and glands (as indicated by the mean cell-to-gland distance) correlated with CD31-positive vessels. B) Mast cells in G2 and G3 tumor specimens show a significant increase in their number as compared to control samples, and their spatial distribution around the glands did not show any significant difference among groups. Overall, the results of this study confirm the important role of macrophages and mast cells in tumor progression and angiogenesis in human ductal breast cancer, and pointed out the spatial relationship between tumor macrophages and glands, and its correlation with microvascular density.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Macrófagos/patologia , Mastócitos/patologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Macrófagos/metabolismo , Mastócitos/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Triptases/metabolismo
12.
Clin Exp Med ; 17(4): 531-539, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28105541

RESUMO

The spatial distribution of mast cells inside the tumor stroma has been little investigated. In this study, we have evaluated tumor mast cells (MCs) distribution in gastric cancer through the analysis of the morphological features of the spatial patterns generated by these cells, including size, shape, and architecture of the cell pattern. The pattern of distribution of tryptase- and chymase-positive MCs around the blood vessels and gastric glands in human gastric adenocarcinoma samples was investigated by immunohistochemical techniques and by introducing a quantitative approach to characterize the spatial distribution of MCs. In human gastric cancer, both chymase-positive MC and vessels exhibited significant deviations from randomness for what it concerns their spatial relationship with gastric parenchyma. As indicated by cell-to-gland distances shorter than expected by chance, in grade II samples a preferential localization of chymase-positive MC near the gastric glands was observed. Interestingly, the same type of spatial association was exhibited by vessels in grade IV samples, where vessel-to-gland distances shorter than expected by chance were observed. These two findings allow to speculate about a sequence of events in which a subpopulation of MC is first recruited around gastric parenchyma to drive the subsequent development of a vascular support to the tissue.


Assuntos
Vasos Sanguíneos/patologia , Carcinoma/patologia , Mastócitos/citologia , Neoplasias Gástricas/patologia , Humanos , Imuno-Histoquímica , Microscopia , Análise Espacial
13.
Clin Exp Med ; 17(1): 71-77, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26886279

RESUMO

Mast cells (MCs) accumulate in the stroma surrounding tumors, where they secrete angiogenic cytokines and proteases, and an increased number of MCs have been demonstrated in angiogenesis associated with solid and hematological tumors. The aim of this study is to contribute to the knowledge of distribution of MCs in tumors, investigating the pattern of distribution of tryptase-positive MCs around the blood vessels in human endometrial carcinoma samples by introducing a quantitative approach to characterize their spatial distribution. The results have shown that in human endometrial cancer bioptic specimens the spatial distribution of MCs shows significant deviation from randomness as compared with control group in which, instead, the spatial distribution of MCs is consistent with a random distribution. These findings confirm that MCs enhance tumor angiogenesis and their preferential localization along blood vessels and sites of new vessel formation sustaining the suggestion for an association between MCs and angiogenesis. However, this spatial association between vessels and MCs might simply reflect migrating MCs from the blood stream at vessel growing sites.


Assuntos
Neoplasias do Endométrio/patologia , Endométrio/patologia , Microvasos/patologia , Neovascularização Patológica/patologia , Contagem de Células , Neoplasias do Endométrio/irrigação sanguínea , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/metabolismo , Endométrio/irrigação sanguínea , Endométrio/metabolismo , Feminino , Expressão Gênica , Humanos , Interpretação de Imagem Assistida por Computador , Imuno-Histoquímica , Mastócitos/metabolismo , Mastócitos/patologia , Microvasos/metabolismo , Gradação de Tumores , Estadiamento de Neoplasias , Neovascularização Patológica/diagnóstico , Neovascularização Patológica/metabolismo , Triptases/genética , Triptases/metabolismo
14.
Int J Mol Sci ; 17(11)2016 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-27809238

RESUMO

Cell death represents the final outcome of several pathological conditions of the central nervous system and available evidence suggests that in both acute injuries and neurodegenerative diseases it is often associated with mitochondrial dysfunction. Thus, the possibility to prevent mitochondrial events involved in cell death might represent efficient tools to limit neuronal damage. In recent years, increased attention has been paid to the endogenous protein neuroglobin, since accumulating evidence showed that its high expression was associated with preserved mitochondrial function and to an increased survival of nerve cells in vitro and in vivo in a variety of experimental models of cell insult. The biological and structural features of neuroglobin and the mitochondria-related mechanisms of neuroglobin-induced neuroprotection will be here briefly discussed. In this respect, the inhibition of the intrinsic pathway of apoptosis emerges as a key neuroprotective effect induced by the protein. These findings could open the possibility to develop efficient neuroglobin-mediated therapeutic strategies aimed at minimizing the neuronal cell death occurring in impacting neurological pathologies like stroke and neurodegenerative diseases.


Assuntos
Globinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Animais , Apoptose , Sobrevivência Celular , Globinas/química , Humanos , Modelos Biológicos , Proteínas do Tecido Nervoso/química , Neuroglobina , Neuroproteção
15.
Am J Physiol Lung Cell Mol Physiol ; 310(7): L680-8, 2016 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-26851258

RESUMO

No papers are available about potentiality of fractal analysis in quantitative assessment of alveolarization in bronchopulmonary dysplasia (BPD). Thus, we here performed a comparative analysis between fractal [fractal dimension (D) and lacunarity] and stereological [mean linear intercept (Lm), total volume of alveolar air spaces, total number of alveoli, mean alveolar volume, total volume and surface area of alveolar septa, and mean alveolar septal thickness] parameters in experimental hyperoxia-induced models of BPD. At birth, rats were distributed between the following groups: 1) rats raised in ambient air for 2 wk; 2) rats exposed to 60% oxygen for 2 wk; 3) rats raised in normoxia for 6 wk; and 4) rats exposed to 60% hyperoxia for 2 wk and to room air for further 4 wk. Normoxic 6-wk rats showed increased D and decreased lacunarity with respect to normoxic 2-wk rats, together with changes in all stereological parameters except for mean alveolar volume. Hyperoxia-exposed 2-wk rats showed significant changes only in total number of alveoli, mean alveolar volume, and lacunarity with respect to equal-in-age normoxic rats. In the comparison between 6-wk rats, the hyperoxia-exposed group showed decreased D and increased lacunarity, together with changes in all stereological parameters except for septal thickness. Analysis of receiver operating characteristic curves showed a comparable discriminatory power of D, lacunarity, and total number of alveoli; Lm and mean alveolar volume were less discriminative. D and lacunarity did not show significant changes when different segmentation thresholds were applied, suggesting that the fractal approach may be fit to automatic image analysis.


Assuntos
Displasia Broncopulmonar/patologia , Alvéolos Pulmonares/patologia , Animais , Feminino , Fractais , Hiperóxia/patologia , Masculino , Modelos Biológicos , Curva ROC , Ratos Sprague-Dawley
16.
Surg Radiol Anat ; 38(3): 341-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26476833

RESUMO

PURPOSE: Recent anatomic investigations of the lateral structures of the knee have rediscovered a ligament, called the antero-lateral ligament (ALL). METHODS: Ten specimens of ALL (6 M, 4 F, mean age 82.3) were sampled from bodies of the Body Donation program of the University of Padova for histological and immuno-histochemical studies. Moreover, a retrospective magnetic resonance (MR) study was carried out in 50 patients (30 M, 20 F, mean age 37.5). MR exams with a normal anatomo-radiological report were selected. RESULTS: From the microscopic point of view the ALL corresponds to a dense connective tissue (mean thickness 893 ± 423 µm), and is composed by collagen I (90 %), collagen III (5 %) and collagen VI (3 %) and scarce elastic fibers (<1 %). On MR exams, ALL appears as a thin linear structure, originating at the lateral epicondyle, running obliquely downwards and forwards, and inserting in the middle third (46 %) or inferior third (14 %) of lateral meniscus and in the lateral aspect of the proximal tibia. It was observed in 47 cases (93 %), with a mean length of 32 ± 4.6 mm and mean thickness of 1.1 ± 0.4 mm. The ALL showed low signal intensity on both T1- and T2-weighted sequences. CONCLUSION: The ALL shows the typical structure of a fibrous ligament. From the anatomo-radiological point of view the ALL is almost constantly depicted by routine 1.5-T MR scan.


Assuntos
Articulação do Joelho/anatomia & histologia , Ligamentos Articulares/anatomia & histologia , Adulto , Idoso de 80 Anos ou mais , Variação Anatômica , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Ligamentos Articulares/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Estudos Retrospectivos
17.
Exp Cell Res ; 339(1): 96-102, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26358232

RESUMO

The spatial distribution of mast cells inside the tumor stroma has been little investigated. In this study, we have evaluated tumor mast cells distribution through the analysis of the morphological features of the spatial patterns generated by these cells, including size, shape, and architecture of the cell pattern. We have compared diffuse large B cells lymphoma (DLBCL) and systemic mastocytosis in two different anatomical localizations (lymph nodes for DLBCL and, respectively, bone marrow for mastocytosis). Results have indicated that, despite the high difference in size exhibited by the mast cells patterns in the two conditions, the spatial relationship between the mast cells forming the aggregates resulted similar, characterized by a significant tendency of the mast cells to self-organize in clusters.


Assuntos
Medula Óssea/patologia , Fractais , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/patologia , Mastócitos/patologia , Mastocitose Sistêmica/patologia , Medula Óssea/imunologia , Humanos , Processamento de Imagem Assistida por Computador , Técnicas Imunoenzimáticas , Linfonodos/imunologia , Linfoma Difuso de Grandes Células B/imunologia , Mastócitos/imunologia , Mastocitose Sistêmica/imunologia , Células Tumorais Cultivadas
18.
Front Physiol ; 5: 432, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25414672

RESUMO

The carotid body (CB) may undergo different structural changes during perinatal development, aging, or in response to environmental stimuli. In the previous literature, morphometric approaches to evaluate these changes have considered quantitative first order parameters, such as volumes or densities, while changes in spatial disposition and/or complexity of structural components have not yet been considered. In the present study, different strategies for addressing morphological complexity of CB, apart from the overall amount of each tissue component, were evaluated and compared. In particular, we considered the spatial distribution of connective tissue in the carotid bodies of young control subjects, young opiate-related deaths and aged subjects, through analysis of dispersion (Morisita's index), gray level co-occurrence matrix (entropy, angular second moment, variance, correlation), and fractal analysis (fractal dimension, lacunarity). Opiate-related deaths and aged subjects showed a comparable increase in connective tissue with respect to young controls. However, the Morisita's index (p < 0.05), angular second moment (p < 0.05), fractal dimension (p < 0.01), and lacunarity (p < 0.01) permitted to identify significant differences in the disposition of the connective tissue between these two series. A receiver operating characteristic (ROC) curve was also calculated to evaluate the efficiency of each parameter. The fractal dimension and lacunarity, with areas under the ROC curve of 0.9651 (excellent accuracy) and 0.8835 (good accuracy), respectively, showed the highest discriminatory power. They evidenced higher level of structural complexity in the carotid bodies of opiate-related deaths than old controls, due to more complex branching of intralobular connective tissue. Further analyses will have to consider the suitability of these approaches to address other morphological features of the CB, such as different cell populations, vascularization, and innervation.

19.
Int J Mol Med ; 33(1): 111-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24270633

RESUMO

Apoptosis represents the key mechanism for the removal of surplus, damaged, or aged cells, and deregulated apoptosis has been implicated in the etiology of diverse pathologies. There are two main pathways which are known to initiate apoptosis: the death receptor-dependent (extrinsic) pathway and the mitochondrial-dependent (intrinsic) pathway. In the intrinsic pathway, as a response to diverse signals from the cellular environment, a permeabilization of the mitochondrial outer membrane occurs, followed by the release of cytochrome c and the activation of the effector caspases, which leads to cell death. Recently, increased attention has been paid to the possible role of the protein neuroglobin, in the regulation of the apoptotic process, and data have been provided, demonstrating the ability of the protein to inhibit the intrinsic pathway of apoptosis by interacting with mitochondrial proteins. The molecular details of these interactions, however, remain largely undefined. In the present study, well recognized bioinformatics methods were applied to predict the possible interaction interfaces which the protein can exploit to interact with relevant proteins of the mitochondrial-dependent pathway of apoptosis. In the search for therapeutic approaches based on the modulation of apoptosis, such a computational prediction could represent a first, guiding step, for the design of strategies aimed at modulating these interactions, and tune the apoptotic process.


Assuntos
Apoptose/fisiologia , Globinas/metabolismo , Mitocôndrias/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Mapeamento de Interação de Proteínas , Morte Celular , Biologia Computacional , Citocromos c/genética , Citocromos c/metabolismo , Globinas/genética , Humanos , Proteínas do Tecido Nervoso/genética , Neuroglobina , Domínios e Motivos de Interação entre Proteínas
20.
Electrophoresis ; 33(24): 3669-79, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23161174

RESUMO

Conformational protein diseases of the human central nervous system represent a subject that has crucial theoretical and medical implications. They include several important neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's and Creutzfeldt-Jacob's diseases, amyotrophic lateral sclerosis, and the tauopathies. They occur when soluble proteins undergo conformational rearrangements becoming capable of aggregate into ß-sheets conformations leading to the production of insoluble complexes known as amyloid deposits, that accumulate and lead to neurons and glial cells death. Theoretical and experimental evidence indicates that a key role in the conformational changes leading to amyloid formation is played by short sequence stretches within a given protein. Thus, the identification of protein regions potentially involved in aggregate formation and the characterization of their properties are relevant questions in the study of conformational proteins diseases. To address these questions, bioinformatics methods might provide an important contribution, suggesting possible mechanisms of protein aggregation, and focusing and orienting the experimental work. Thus, in the first part of the present review bioinformatics methods specifically attempting to predict aggregation-prone regions in proteins will be briefly described. Furthermore, the results provided by the combined use of some of them to analyze a set of particularly important proteins involved in human degenerative diseases will be discussed.


Assuntos
Amiloidose/metabolismo , Biologia Computacional/métodos , Doenças Neurodegenerativas/metabolismo , Algoritmos , Amiloide/metabolismo , Humanos , Modelos Estatísticos , Software
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