Person:
Murillo González, Jorge Alfonso

First Name

Jorge Alfonso

Last Name

Murillo González

URI

https://hdl.handle.net/20.500.14352/79209

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Medicina

Department

Anatomía y Embriología

Area

Anatomía y Embriología Humana

Identifiers

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Now showing 1 - 10 of 30

Interactions between TGF-β1 and TGF-β3 and their role in medial edge epithelium cell death and palatal fusion in vitro
(Differentiation, 2008) Murillo González, Jorge Alfonso; Maldonado Bautista, Estela; Barrio Asensio, María Del Carmen; Río Sevilla, Aurora Del; López, Yamila; Martínez Sanz, Elena; González, Ignacio; Martín, Concepción; Casado, Inmaculada; Martínez Álvarez, María Concepción
In recent decades, studies have shown that both TGF-beta(1) and TGF-beta(3) play an important role in the induction of medial edge epithelium (MEE) cell death and palatal fusion. Many of these experiments involved the addition or blockage of one of these growth factors in wild-type (WT) mouse palate cultures, where both TGF-beta(1) and TGF-beta(3) are present. Few studies have addressed the existence of interactions between TGF-beta(1) and TGF-beta(3), which could modify their individual roles in MEE cell death during palatal fusion. We carried out several experiments to test this possibility, and to investigate how this could influence TGF-beta(1) and TGF-beta(3) actions on MEE cell death and palatal shelf fusion. We double-immunolabelled developing mouse palates with anti-TGF-beta(1) or anti-TGF-beta(3) antibodies and TUNEL, added rhTGF-beta(1) or rhTGF-beta(3) or blocked the TGF-beta(1) and TGF-beta(3) action at different concentrations to WT or Tgf-beta(3) null mutant palate cultures, performed in situ hybridizations with Tgf-beta(1) or Tgf-beta(3) riboprobes, and measured the presence of TUNEL-positive midline epithelial seam (MES) cells and MES disappearance (palatal shelf fusion) in the different in vitro conditions. By combining all these experiments, we demonstrate great interaction between TGF-beta(1) and TGF-beta(3) in the developing palate and confirm that TGF-beta(3) has a more active role in MES cell death than TGF-beta(1), although both are major inductors of MES disappearance. Finally, the co-localization of TGF-beta(1), but not TGF-beta(3), with TUNEL in the MES allows us to suggest a possible role for TGF-beta(1) in MES apoptotic clearance.
Occurrence of cleft-palate and alteration of Tgf-β3 expression and the mechanisms leading to palatal fusion in mice following dietary folic-acid deficiency
(Cells Tissues Organs, 2011) Maldonado Bautista, Estela; Murillo González, Jorge Alfonso; Barrio Asensio, María Del Carmen; Río Sevilla, Aurora Del; Pérez De Miguelsanz, María Juliana; López Gordillo, Yamila; Partearroyo, Teresa; Paradas Lara, Irene; Maestro De Las Casas, María Del Carmen; Martínez Sanz, Elena; Varela Moreiras, Gregorio; Martínez Álvarez, María Concepción
Folic acid (FA) is essential for numerous bodily functions. Its decrease during pregnancy has been associated with an increased risk of congenital malformations in the progeny. The relationship between FA deficiency and the appearance of cleft palate (CP) is controversial, and little information exists on a possible effect of FA on palate development. We investigated the effect of a 2–8 weeks’ induced FA deficiency in female mice on the development of CP in their progeny as well as the mechanisms leading to palatal fusion, i.e. cell proliferation, cell death, and palatal-shelf adhesion and fusion. We showed that an 8 weeks’ maternal FA deficiency caused complete CP in the fetuses although a 2 weeks’ maternal FA deficiency was enough to alter all the mechanisms analyzed. Since transforming growth factor beta 3 (TGF-β3) is crucial for palatal fusion and since most of the mechanisms impaired by FA deficiency were also observed in the palates of Tgf-β3 null mutant mice, we investigated the presence of TGF-beta 3 mRNA, its protein and phospho-SMAD2 in FA-deficient (FAD) mouse palates. Our results evidenced a large reduction in Tgf-β3 expression in palates of embryos of dams fed an FAD diet for 8 weeks; Tgf-β3 expression was less reduced in palates of embryos of dams fed an FAD diet for 2 weeks. Addition of Tgf-β3 to palatal-shelf cultures of embryos of dams fed an FAD diet for 2 weeks normalized all the altered mechanisms. Thus, an insufficient folate status may be a risk factor for the development of CP in mice, and exogenous Tgf-β3 compensates this deficit in vitro.
Project number: 114
Desarrollo de un sistema interactivo para el estudio de la órbita y su contenido: anatomía microscópica
(2022) Barrio Asensio, María Del Carmen; Arráez Aybar, Luis Alfonso; Catón Vázquez, Francisco Javier; García Serradilla, Moisés; García-Mauriño Múzquiz, José Enrique; Maldonado Bautista, Estela; Martínez Sanz, Elena; Mérida Velasco, José Ramón; Murillo Barrio, Jaime; Murillo González, Jorge Alfonso; Paradas Lara, Irene
Se ha desarrollado un sistema interactivo para mejorar el proceso de enseñanza-aprendizaje en la docencia de la anatomía microscópica de la órbita y su contenido, a través de preparaciones histológicas. Se pretende facilitar el aprendizaje de forma autónoma en español e inglés y, la autoevaluación sobre los conocimientos adquiridos.
X-ray micro-computed tomography of postmortem brain tissue using potassium dichromate as a contrast agent
(Archives Italiennes de Biologie, 2018) Notario, B.; Barrio Asensio, María Del Carmen; Herrera Lara, Manuel Eugenio; B.D. METSCHER; Murillo González, Jorge Alfonso
n/a
Maternal folic acid supplementation reduces the severity of cleft palate in Tgf-β3 null mutant mice
(Pediatric research, 2019) López Gordillo, Yamila; Maldonado Bautista, Estela; Nogales, Laura; Río Sevilla, Aurora Del; Barrio Asensio, María Del Carmen; Murillo González, Jorge Alfonso; Martínez Sanz, Elena; Paradas Lara, Irene; Alonso Revuelta, María Isabel; Partearroyo, Teresa; Martínez Álvarez, María Concepción
BACKGROUND: Cleft palate (CP) constitutes the most frequently seen orofacial cleft and is often associated with low folate status. Folate plays an essential role in the human body as a major coenzyme in one-carbon metabolism, including DNA synthesis, repair, and methylation. Whether the administration of isolated folic acid (FA) supplements prevents the CP caused by genetic mutations is unknown, as is its effect on the mechanisms leading to palate fusion. METHODS: FA was administered to females from two different strains of transforming growth factor β3 heterozygous mice. Null mutant progeny of these mice exhibit CP in 100% of cases of varying severity. We measured cleft length, height of palatal shelf adhesion, and the number of proliferating mesenchymal cells. Immunohistochemistry was also carried for collagen IV, laminin, fibronectin, cytokeratin-17, and EGF. RESULTS: FA supplementation significantly reduced CP severity and improved palatal shelf adhesion in both strains both in vivo and in vitro. Medial edge epithelium proliferation increased, and its differentiation was normalized as indicated by the presence and disposition of collagen IV, laminin, fibronectin, and cytokeratin-17. CONCLUSIONS: A maternal FA supplementation reduces the CP appearance by improving the mechanisms leading to palatal shelf adhesion.
Basic morphological characteristics of coracoid grafts obtained by open and arthroscopic Latarjet techniques: A comparative study
(Orthopaedics & Traumatology: Surgery & Research, 2020) Minuesa Asensio, Álvaro José; García Esteo, Francisco; Mérida Velasco, José Ramón; Barrio Asensio, María Del Carmen; Cuadra Blanco, Crótida de la; Murillo González, Jorge Alfonso
Background: A knowledge of the anthropometric characteristics of the coracoid graft (CG) that can be obtained by the open and arthroscopic Latarjet techniques may be beneficial in the preoperative planning and intraoperative decision making for coracoid osteotomy and transfer. We have not found any study that compared the morphology of the CG that can be obtained from open and arthroscopic Latarjet techniques. The purpose of this study was to verify if the basic anthropometric characteristics of CGs are equivalent. Hypothesis: We hypothesize that the basic anthropometric characteristics of the CGs are similar. Methods: Twenty fresh-frozen human paired cadaveric shoulder specimens that had been randomly distributed in two groups of 10 specimens each were used. Two surgeons, each with experience in performing the open and arthroscopic Latarjet technique, performed these procedures in each of the respective groups (OG, open group; AG, arthroscopic group). A CT scan was performed. Using the volume rendering technique, a metric analysis of the volume, area and length of the CG were performed, evaluated and statistically analysed. Results: There were no significant differences in length (p = 0.162) (mean length, 22.6 mm for OG and 23.6 mm for AG). There were significant differences in the volume (p = 0.031) and area (p = 0.007) of the CG, being lower in the OG (mean volume, 2.8 cm3 for OG and 3.6 cm3 for AG; mean area, 9.9 cm2 for OG and 12.8 cm2 for AG). No significant differences were observed by sex or laterality. Conclusion: The mean lengths of the CGs that were obtained by each technique are equivalent. However, the areas and volumes of the grafts are different, being lower in the open surgery. These differences have not been an impediment to perform the technique. Our results corroborates that consolidation is more related to the preparation and placement than to the anthropometric characteristics of the CG. No significant differences were observed by sex or laterality.
Epidermal Growth Factor Impairs Palatal Shelf Adhesion and Fusion in the T gf-β3 Null Mutant
(Cells Tissues Organs, 2014) Barrio Asensio, María Del Carmen; Río Sevilla, Aurora Del; Murillo González, Jorge Alfonso; Maldonado Bautista, Estela; López Gordillo, Yamila; Paradas Lara, Irene; Hernandes, Luzmarina; Catón Vázquez, Francisco Javier; Martínez Álvarez, María Concepción
The cleft palate presented by transforming growth factor-β3 (Tgf-β3 ) null mutant mice is caused by altered palatal shelf adhesion, cell proliferation, epithelial-to-mesenchymal transformation and cell death. The expression of epidermal growth factor (EGF), transforming growth factor-β1 ( Tgf-β1 ) and muscle segment homeobox-1 (Msx-1) is modified in the palates of these knockout mice, and the cell proliferation defect is caused by the change in EGF expression. In this study, we aimed to determine whether this change in EGF expression has any effect on the other mechanisms altered in Tgf-β 3 knockout mouse palates. We tested the effect of inhibiting EGF activity in vitro in the knockout palates via the addition of Tyrphostin AG 1478. We also investigated possible interactions between EGF, Tgf-β 1 and Msx-1 in Tgf-β 3 null mouse palate cultures. The results show that the inhibition of EGF activity in Tgf-β 3 null mouse palate cultures improves palatal shelf adhesion and fusion, with a particular effect on cell death, and restores the normal distribution pattern of Msx-1 in the palatal esenchyme. Inhibition of TGF-β 1 does not affect either EGF or Msx-1 expression.
Study of the functional relationships between the buccinator muscle and the connective tissue of the cheek in humans
(Annals of Anatomy, 2022) Martínez Sanz, Elena; Catón Vázquez, Francisco Javier; Maldonado Bautista, Estela; Murillo González, Jorge Alfonso; Barrio Asensio, María Del Carmen; Paradas Lara, Irene; García Serradilla, Moisés; Arráez Aybar, Luis Alfonso; Mérida Velasco, José Ramón
Background: The buccinator muscle derives from the mesenchyme of the second pharyngeal arch. In adults, it has a quadrilateral shape, occupying the deepest part of the cheek region. Its function is complex, being active during swallowing, chewing, and sucking. To our knowledge, there are no studies that have specifically analyzed the relationship of the buccinator muscle fibers and neighboring connective tissue of the cheek in humans, neither during development nor in adults. Such relationships are fundamental to understand its function. Thus, in this study the relations of the buccinator muscle with associated connective tissue were investigated. Methods: The buccinator muscle region was investigated bilaterally in 41 human specimens of 8–17 weeks of development. Moreover, four complete adult tissue blocks from human cadavers (including mucosa and skin) were obtained from the cheek region (between the anterior border of the masseter muscle and the nasolabial fold). All samples were processed with standard histological techniques. In addition, subsets of sections were stained with picrosirius red (PSR). Furthermore, immunoreactivity against type I and III collagen was also studied in adult tissues. Results: The buccinator muscle showed direct relationships with its connective tissue from 8 to 17 weeks of development. Collagen fibers were arranged in septa from the submucosa to the skin through the muscle. These septa were positive for type I collagen and presented elastic fibers. Fibrous septa that were positive for type III collagen were arranged from the lateral side of the muscle to the skin. Conclusions: The intimate relationship between buccinator muscle fibers and cheek connective tissue may explain the complex functions of this muscle.
In Vitro Manipulation of Cleft Palate Connective Tissue: Setting the Bases of a Proposed New Treatment
(Journal of Surgical Research, 2006) Resel, Eva; Martínez Sanz, Elena; González, Ignacio; Trinidad, Eva; Garcillán, Beatriz; Amorós, María; Alonso Bañuelos, Carmen; González Meli, Beatriz; Lagarón, Emilio; Murillo González, Jorge Alfonso; Río Sevilla, Aurora Del; Barrio Asensio, María Del Carmen; López, María; Martínez Álvarez, María Concepción
Background. Palatoplasty has the undesired side effect of impaired mid-facial growth. To avoid this problem, we propose an alternative to palatoplasty. We hypothesize that if BMP-2 is injected together with a carrier into the periosteum of the cleft palate borders, border volume will increase and connective tissue cells will be activated to produce extra bone. Once these borders supported by bone reach the midline, extraction of their covering epithelia with trypsin will permit adhesion of the underlying tissues. We investigated in vitro the ability of cleft palate connective tissue cells to produce extra bone in the presence of BMP-2 and the possibility of using trypsin to remove the epithelium covering the cleft palate borders without impairing the underlying tissues’ ability to adhere. Materials and methods. We used the cleft palate presented by tgf- 3 null mice and small fragments of human cleft palate mucoperiosteum as models. Immunolabeling BMP-2-treated or untreated cultures with TUNEL and anti-osteocalcin or PCNA antibodies was performed. The epithelium of the cleft palate borders was removed with a trypsin solution, and the deepithelialized tissues were cultured in apposition. Results. BMP-2 induces differentiation toward bone on cleft palate connective tissue cells without producing cell death or proliferation. Trypsin removal of the cleft palate margins’ epithelium does not impair the underlying tissues’ adhesion. Conclusion. It is possible to generate extra bone at the cleft palate margins and to chemically eliminate their covering epithelia without damaging the underlying tissues, which allows further investigation in vivo of this new approach for cleft palate closure.
Arthroscopic stabilisation of an acute acromioclavicular dislocation grade III in a patient with ectopic insertion of the pectoralis minor: technical considerations
(Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA, 2016) Minuesa Asensio, Álvaro; Barrio Asensio, María Del Carmen; González Gómez, Ignacio; Murillo González, Jorge Alfonso
The different approaches used in arthroscopic stabilisation of the acromioclavicular joint are well known. However, and despite a great incidence of ectopic pectoralis minor insertion, an alternative choice for the use of arthroscopic portal has not being sufficiently described. Here, we describe a case of acute acromioclavicular dislocation grade III. The arthroscopic stabilisation was achieved using the TightRope (Arthrex, Naples, USA) implant. Through this technique, the approach to the articular portion of the coracoid process can be made intra-articularly or from the subacromial space. We accessed intra-articularly, by opening the rotator interval to reach the coracoid process from the joint cavity. After opening the rotator interval, an ectopic insertion of the pectoralis minor was observed. The choice of approach of the coracoid process from the subacromial space would have complicated the intervention, making it necessary to sever the ectopic tendon to complete the technique, lengthening the surgical time and increasing the chance of complications. For this reason, the use of a standard posterior portal providing intra-articular arthroscopic access through the rotator interval is recommended since the aforementioned anatomical variation is not infrequent. Level of evidence Therapeutic studies—investigating the results of treatment, Level V.