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1.
Physiol Rep ; 11(13): e15737, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37401248

RESUMO

Pulmonary hypoplasia and respiratory failure are primary causes of death in patients with osteogenesis imperfecta (OI) type II. OI is a genetic skeletal disorder caused by pathogenic variants in genes encoding collagen type I. It is still unknown if the collagen defect also affects lung development and structure, causing lung hypoplasia in OI type II. The aim of this study was to investigate the intrinsic characteristics of OI embryonic lung parenchyma and to determine whether altered collagen type I may compromise airway development and lung structure. Lung tissue from nine fetuses with OI type II and six control fetuses, matched by gestational age, was analyzed for TTF-1 and collagen type I expression by immunohistochemistry, to evaluate the state of lung development and amount of collagen. The differentiation of epithelium into type 2 pneumocytes during embryonic development was premature in OI type II fetuses compared to controls (p < 0.05). Collagen type I showed no significant differences between the two groups. However, the amount of alpha2(I) chains was higher in fetuses with OI and the ratio of alpha1(I) to alpha2(I) lower in OI compared to controls. Cell differentiation during lung embryonic development in patients with OI type II is premature and impaired. This may be the underlying cause of pulmonary hypoplasia. Altered cell differentiation can be secondary to mechanical chest factors or a consequence of disrupted type I collagen synthesis. Our findings suggest that collagen type I is a biochemical regulator of pulmonary cell differentiation, influencing lung development.


Assuntos
Colágeno Tipo I , Osteogênese Imperfeita , Humanos , Colágeno Tipo I/genética , Osteogênese Imperfeita/complicações , Osteogênese Imperfeita/genética , Osteogênese Imperfeita/patologia , Colágeno/metabolismo , Diferenciação Celular
2.
Br J Oral Maxillofac Surg ; 58(1): 96-98, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563484

RESUMO

Fibrous dysplasia may show locally aggressive behaviour reflecting secondary intralesional changes, extension to soft tissue, or malignant transformation. We report the case of a patient with polyostotic fibrous dysplasia who had a giant mandibular lesion consisting of histologically typical, genotypically-confirmed, fibrous dysplasia merged with a fibrotic and hypocellular desmoplastic fibroma-like tissue in which the same Gsα-R201H mutation was detected. The occurrence of the same mutation in both the fibrous dysplasia and areas of desmoplastic fibroma suggests that the fibroma-like tissue reflects an unusual secondary tissue change within an otherwise typical fibrous dysplasia. To the best of our knowledge, only four cases of fibrous dysplasia with desmoplastic fibroma-like tissue changes have been reported.


Assuntos
Neoplasias Ósseas , Fibroma Desmoplásico , Fibroma , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Mutação
3.
Leukemia ; 29(6): 1360-5, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25650091

RESUMO

In order to evaluate the predictive value of positron emission tomography-computed tomography (PET/CT) in discriminating the presence of a Richter's syndrome (RS) or a second malignancy (SM), as well as to evaluate its prognostic value in patients with chronic lymphocytic leukemia (CLL), we retrospectively analyzed the data of 90 patients who, in the suspicion of a RS or a SM, underwent PET/CT followed by the biopsy of the involved tissue. The median maximum Standardized Uptake Value (SUV max) in the presence of a CLL/small lymphocytic lymphoma, a diffuse large B-cell lymphoma (DLBCL), a Hodgkin lymphoma (HL), a SM were 3.5, 14.6, 7.0 and 6.3, respectively (P ⩽ 0.0001). A SUV max cutoff value ⩾ 5 showed a sensitivity, specificity, positive and negative predictive values of 88.2, 71.2, 51.3 and 94%, respectively, for the presence of a more aggressive disease (DLBCL, HL and SM). A SUV max ⩾ 5 identified also a subset of treatment naive patients with an inferior progression-free survival (P = 0.011) and overall survival (P = 0.067). These findings suggest that PET/CT may helpfully integrate the biologically-based prognostic stratification of CLL. Prospective clinical trials including larger cohorts of patients are needed to conclusively define the role and prognostic impact of PET/CT in the routine management of CLL patients.


Assuntos
Doença de Hodgkin/diagnóstico , Leucemia Linfocítica Crônica de Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/terapia , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
4.
Infection ; 41(1): 255-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23007326

RESUMO

A rare case of splenic marginal zone lymphoma (SMZL) in a human immunodeficiency virus (HIV)-1 infected patient is described. As an association between SMZL and viral infections has been reported, the presence of the hepatitis C virus and HIV-1 genomes was evaluated. Only HIV-1 DNA levels were detected in enriched splenic B lymphocytes, suggesting a HIV-1 involvement in lymphomagenesis.


Assuntos
Infecções por HIV/complicações , HIV-1/patogenicidade , Linfoma de Zona Marginal Tipo Células B/etiologia , Neoplasias Esplênicas/etiologia , Transformação Celular Viral , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Pessoa de Meia-Idade , Baço/patologia , Neoplasias Esplênicas/diagnóstico
5.
Int J Oral Maxillofac Surg ; 39(8): 793-801, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20417057

RESUMO

Maxillary sinus membrane lifting is a common procedure aimed at increasing the volume of the maxillary sinus osseous floor prior to inserting dental implants. Clinical observations of bone formation in sinus lifting procedures without grafting bone substitutes were observed, but the biological nature of bone regeneration in sinus lifting procedures is unclear. This study tested whether this osteogenic activity relies on inherent osteogenic capacity residing in the sinus membrane by simulating the in vivo clinical condition of sinus lifting in an animal model. Maxillary sinus membrane cells were cultured in alpha-MEM medium containing osteogenic supplements (ascorbic acid, dexamethasone). Cultured cells revealed alkaline phosphatase activity and mRNA expression of osteogenic markers (alkaline phosphatase, bone sialoprotein, osteocalcin and osteonectin) verifying the osteogenic potential of the cells. Fresh tissue samples demonstrated positive alkaline phosphatase enzyme activity situated along the membrane-bone interface periosteum-like layer. To simulate the in vivo clinical conditions, the membranes were folded to form a pocket-like structure and were transplanted subcutaneously in immunodeficient mice for 8 weeks. New bone formation was observed in the transplants indicating the innate osteogenic potential within the maxillary Schneiderian sinus membrane and its possible contribution to bone regeneration in sinus lifting procedures.


Assuntos
Células-Tronco Adultas/citologia , Regeneração Óssea/fisiologia , Mucosa Nasal/citologia , Osteoblastos/citologia , Osteogênese/fisiologia , Adolescente , Adulto , Células-Tronco Adultas/metabolismo , Células-Tronco Adultas/transplante , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Bioensaio , Calcificação Fisiológica/fisiologia , Humanos , Sialoproteína de Ligação à Integrina/genética , Sialoproteína de Ligação à Integrina/metabolismo , Seio Maxilar , Camundongos , Camundongos Nus , Osteoblastos/metabolismo , Osteoblastos/transplante , Osteocalcina/genética , Osteocalcina/metabolismo , Osteonectina/genética , Osteonectina/metabolismo , RNA Mensageiro/análise , Transplante Heterólogo , Adulto Jovem
6.
Calcif Tissue Int ; 84(2): 138-45, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19067018

RESUMO

Recent studies successfully demonstrated induction of new bone formation in the maxillary sinus by mucosal membrane lifting without the use of any graft material. The aim of this work was to test the osteogenic potential of human maxillary sinus Schneiderian membrane (hMSSM) using both in vitro and in vivo assays. Samples of hMSSM were used for establishment of cell cultures and for histological studies. Flow cytometry analysis was performed on P(0), P(1), and P(2) cultures using established mesenchymal progenitor cell markers (CD 105, CD 146, CD 71, CD 73, CD 166), and the ability of hMSSM cells to undergo osteogenic differentiation in culture was analyzed using relevant in vitro assays. Results showed that hMSSM cells could be induced to express alkaline phosphatase, bone morphogenic protein-2, osteopontin, osteonectin, and osteocalcin and to mineralize their extracellular matrix. Inherent osteogenic potential of hMSSM-derived cells was further proven by in vivo experiments, which demonstrated the formation of histology-proven bone at ectopic sites following transplantation of hMSSM-derived cells in conjunction with an osteoconductive scaffold. This study provides the biological background for understanding the observed clinical phenomena in sinus lifting. Our results show that a genuine osteogenic potential is associated with the hMSSM and can contribute to development of successful sinus augmentation techniques.


Assuntos
Mucosa Nasal/citologia , Osteoblastos/citologia , Células-Tronco/citologia , Animais , Calcificação Fisiológica , Diferenciação Celular , Células Cultivadas , Humanos , Camundongos , Camundongos Nus , Mucosa Nasal/química , Mucosa Nasal/metabolismo , Osteoblastos/metabolismo , Osteoblastos/transplante , Osteogênese , Células-Tronco/metabolismo
7.
Cell Prolif ; 41(6): 909-922, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19040569

RESUMO

OBJECTIVES: Mesenchymal stromal cells (MSCs) have attracted considerable interest in both the scientific and clinical fields. In order to obtain a sufficient cell number for application, their in vitro expansion is necessary, but during this process their characteristics may be altered and cells may acquire oncogenic properties. We have investigated properties of MSC that may be related to oncogenesis, a critical parameter that has to be evaluated prior to MSC clinical use. MATERIALS AND METHODS: We studied the expression of p53, p16, RB, H-RAS and human telomerase reverse transcriptase (hTERT) in MSCs from bone marrow of children diagnosed with idiopathic thrombocytopenic purpura (ITP) and autoimmune neutropenia. The same cells were seeded in soft agar to confirm their anchorage dependence and were karyotypically analysed. Finally, MSCs were subcutaneously transplanted into SCID mice and their ectopic osteogenic as well as tumorigenic potential was evaluated. RESULTS: We have shown that MSCs derived from bone marrow of children with ITP and autoimmune neutropenia do not undergo transformation, the cells expressed normal levels of p53, p16, RB and H-RAS. Expression of hTERT was undetectable, chromosome content remained stable, and their anchorage dependence was confirmed. In an in vivo model, when MSCs were subcutaneously transplanted into SCID mice, no tumorigenesis was observed. CONCLUSIONS: These findings suggest that MSCs from bone marrow of children do not have oncogenic properties and, therefore, represent validate candidates for applications in regenerative medicine.


Assuntos
Células da Medula Óssea/patologia , Transformação Celular Neoplásica/patologia , Células-Tronco Mesenquimais/patologia , Animais , Células da Medula Óssea/efeitos dos fármacos , Matriz Óssea/efeitos dos fármacos , Matriz Óssea/patologia , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Criança , Pré-Escolar , Fator 2 de Crescimento de Fibroblastos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Genes Supressores de Tumor , Humanos , Lactente , Cariotipagem , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/enzimologia , Camundongos , Camundongos SCID , Oncogenes , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Estromais/efeitos dos fármacos , Células Estromais/patologia , Telomerase/genética , Telomerase/metabolismo
8.
Bone ; 42(2): 321-31, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18063434

RESUMO

Parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) regulate calcium homeostasis, and PTHrP further regulates growth and development. A transgenic mouse carrying the constitutively active PTH/PTHrP receptor (HKrk-H223R) under the control of the mouse bone and odontoblast-specific alpha1(I) collagen promoter (Col1-caPPR) has been developed to demonstrate the complex actions of this mutant receptor in hard tissue formation. We have further characterized Col1-caPPR mice abnormalities in the craniofacial region as a function of development. Col1-caPPR mice exhibited a delay in embryonic bone formation, followed by expansion of a number of craniofacial bones including the maxilla and mandible, delay in tooth eruption and teratosis, and a disrupted temporomandibular joint (TMJ). These findings suggest that the Col1-caPPR mouse is a useful model for characterization of the downstream effects of the constitutively active receptor during development and growth, and as a model for development of treatments of human diseases with similar characteristics.


Assuntos
Ossos Faciais/embriologia , Ossos Faciais/crescimento & desenvolvimento , Hormônio Paratireóideo/metabolismo , Animais , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Embrião de Mamíferos/diagnóstico por imagem , Embrião de Mamíferos/embriologia , Embrião de Mamíferos/metabolismo , Ossos Faciais/diagnóstico por imagem , Ossos Faciais/metabolismo , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Microscopia Eletrônica de Varredura , Hormônio Paratireóideo/genética , Regiões Promotoras Genéticas/genética , Tomografia Computadorizada por Raios X
9.
Calcif Tissue Int ; 78(6): 372-84, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16830199

RESUMO

Systems for gene transfer and silencing in human skeletal stem cells (hSSCs, also stromal or mesenchymal stem cells) are important for addressing critical issues in basic hSSC and skeletal biology and for developing gene therapy strategies for treatment of skeletal diseases. Whereas recent studies have shown the efficacy of lentiviral transduction for gene transfer in hSSCs in vitro, no study has yet proven that lentivector-transduced hSSCs retain their distinctive organogenic potential in vivo, as probed by in vivo transplantation assays. Therefore, in addition to analyzing the in vitro growth and differentiation properties of hSSCs transduced with advanced-generation lentivectors, we ectopically transplanted LV-eGFP-transduced hSSCs (along with an osteoconductive carrier) in the subcutaneous tissue of immunocompromised mice. eGFP-transduced cells formed heterotopic ossicles, generating osteoblasts, osteocytes, and stromal cells in vivo, which still expressed GFP at 2 months after transplantation. eGFP-expressing cells could be recovered from the ossicles 8 weeks posttransplantation and reestablished in culture as viable and proliferating cells. Further, we investigated the possibility of silencing individual genes in hSSCs using lentivectors encoding short hairpin precursors of RNA interfering sequences under the control of the Pol-III-dependent H1 promoter. Significant long-term silencing of both lamin A/C and GFP (an endogenous gene and a transgene, respectively) was obtained with lentivectors encoding shRNAs. These data provide the basis for analysis of the effect of gene knockdown during the organogenesis of bone in the in vivo transplantation system and for further studies on the silencing of alleles carrying dominant, disease-causing mutations.


Assuntos
Inativação Gênica/fisiologia , Lentivirus/genética , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Transdução Genética , Doenças Ósseas/terapia , Células Cultivadas , Regulação da Expressão Gênica/fisiologia , Terapia Genética , Vetores Genéticos , Proteínas de Fluorescência Verde/genética , Humanos , Lamina Tipo A/genética , Células-Tronco Mesenquimais/citologia , Fosfoglicerato Quinase/genética , Interferência de RNA/fisiologia , RNA Interferente Pequeno/genética
10.
Pathologica ; 97(4): 186, 2005 Aug.
Artigo em Italiano | MEDLINE | ID: mdl-16440648
11.
Calcif Tissue Int ; 73(3): 281-9, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14667142

RESUMO

Bone sialoprotein (BSP) is a member of the SIBLINGS family, normally restricted to the skeleton, but it has been shown to be ectopically expressed in some human invasive carcinomas. BSP expression in human cancer was initially associated with the ability of BSP-expressing tumors to metastasize to bone, although the mechanism whereby BSP expression should facilitate homing of cancer cells to the bone marrow environment has remained unexplained. More recently, clinical and experimental data have converged in highlighting a potential link between BSP expression and tumor invasiveness in general. We show here that human malignant melanoma cells express BSP in vivo as a function of extent of local invasion, and that expression of BSP mRNA and protein in melanoma cells is associated with the expression of the transcriptional regulator of osteogenic cell differentiation, Cbfa1/Runx2. It has been well established that expression of Cbfa1/Runx2 in the mouse is normally restricted to bone-forming cells. In the mouse, Cbfa1/Runx2 dictates osteogenic differentiation of mesodermal cells by regulating bone-specific genes. Since it also regulates expression of at least two matrix metalloproteases implicated in tumor invasion and metastasis (collagenase 3, membrane type 1 matrix metalloproteinase), we propose that the relationship between BSP expression and an invasive behavior in human epithelial cancer cells may be rooted in a common transcriptional control exerted by Cbfa1.


Assuntos
Regulação Neoplásica da Expressão Gênica , Melanoma/metabolismo , Proteínas de Neoplasias/metabolismo , Sialoglicoproteínas/metabolismo , Neoplasias Cutâneas/metabolismo , Fatores de Transcrição/metabolismo , Linhagem Celular Tumoral , Subunidade alfa 1 de Fator de Ligação ao Core , Primers do DNA/química , Técnica Direta de Fluorescência para Anticorpo , Humanos , Sialoproteína de Ligação à Integrina , Melanoma/genética , Melanoma/secundário , Microscopia de Fluorescência , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteossarcoma , RNA Mensageiro/metabolismo , RNA Neoplásico/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sialoglicoproteínas/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Fatores de Transcrição/genética
12.
Bone ; 33(3): 434-42, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-13678786

RESUMO

Fibrous dysplasia of bone (FD) is caused by somatic mutations of the GNAS1 gene, which lead to constitutive activation of adenylyl cyclase and overproduction of cAMP in osteogenic cells. Previous in vitro studies using nonclonal, heterogeneous strains of FD-derived cells suggested that IL-6 might play a critical role in promoting excess osteoclastogenesis in FD. In this study, we investigated IL-6 expression in FD in situ and its relationship to the actual patterns of osteoclastogenesis within the abnormal tissue. We found that osteoclastogenesis is not spatially restricted to bone surfaces in FD but occurs to a large extent ectopicly in the fibrous tissue, where stromal cells diffusely express IL-6 mRNA and exhibit a characteristic cell morphology. We also observed specific expression of IL-6 mRNA in a proportion of osteoclasts, suggesting that an autocrine/paracrine loop may contribute to osteoclastogenesis in vivo in FD, as in some other bone diseases, including Paget's disease. We also generated homogeneous, clonally derived strains of wild-type and GNAS1-mutated stromal cells from the same individual, parent FD lesions. In this way, we could show that mutated stromal cells produce IL-6 at a basal magnitude and rate that are significantly higher than in the cognate wild-type cells. Conversely, wild-type cells respond to db-cAMP with a severalfold increase in magnitude and rate of IL-6 production, whereas mutant strains remain essentially unresponsive. Our data establish a direct link between GNAS1 mutations in stromal cells and IL-6 production but also define the complexity of the role of IL-6 in regulating osteoclastogenesis in FD in vivo. Here, patterns of osteoclastogenesis and bone resorption reflect not only the cell-autonomous effects of GNAS1 mutations in osteogenic cells (including IL-6 production) but also the local and systemic context to which non-osteogenic cells, local proportions of wild-type vs mutated cells, and systemic hormones contribute.


Assuntos
Displasia Fibrosa Óssea/patologia , Displasia Fibrosa Óssea/fisiopatologia , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Interleucina-6/genética , Osteoclastos/citologia , Osteoclastos/fisiologia , Adulto , Divisão Celular/fisiologia , Criança , Cromograninas , Feminino , Expressão Gênica , Humanos , Técnicas In Vitro , Masculino , Mutagênese , Células Estromais/citologia , Células Estromais/fisiologia
13.
Braz. j. med. biol. res ; 36(8): 1027-1036, Aug. 2003. ilus
Artigo em Inglês | LILACS | ID: lil-340794

RESUMO

Deposition of bone in physiology involves timed secretion, deposition and removal of a complex array of extracellular matrix proteins which appear in a defined temporal and spatial sequence. Mineralization itself plays a role in dictating and spatially orienting the deposition of matrix. Many aspects of the physiological process are recapitulated in systems of autologous or xenogeneic transplantation of osteogenic precursor cells developed for tissue engineering or modeling. For example, deposition of bone sialoprotein, a member of the small integrin-binding ligand, N-linked glycoprotein family, represents the first step of bone formation in ectopic transplantation systems in vivo. The use of mineralized scaffolds for guiding bone tissue engineering has revealed unexpected manners in which the scaffold and cells interact with each other, so that a complex interplay of integration and disintegration of the scaffold ultimately results in efficient and desirable, although unpredictable, effects. Likewise, the manner in which biomaterial scaffolds are "resorbed" by osteoclasts in vitro and in vivo highlights more complex scenarios than predicted from knowledge of physiological bone resorption per se. Investigation of novel biomaterials for bone engineering represents an essential area for the design of tissue engineering strategies


Assuntos
Humanos , Materiais Biocompatíveis , Engenharia Biomédica , Biotecnologia , Osso e Ossos , Substitutos Ósseos , Matriz Extracelular , Transplante Ósseo , Técnicas de Cultura de Células , Transplante de Células
14.
Braz J Med Biol Res ; 36(8): 1027-36, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12886456

RESUMO

Deposition of bone in physiology involves timed secretion, deposition and removal of a complex array of extracellular matrix proteins which appear in a defined temporal and spatial sequence. Mineralization itself plays a role in dictating and spatially orienting the deposition of matrix. Many aspects of the physiological process are recapitulated in systems of autologous or xenogeneic transplantation of osteogenic precursor cells developed for tissue engineering or modeling. For example, deposition of bone sialoprotein, a member of the small integrin-binding ligand, N-linked glycoprotein family, represents the first step of bone formation in ectopic transplantation systems in vivo. The use of mineralized scaffolds for guiding bone tissue engineering has revealed unexpected manners in which the scaffold and cells interact with each other, so that a complex interplay of integration and disintegration of the scaffold ultimately results in efficient and desirable, although unpredictable, effects. Likewise, the manner in which biomaterial scaffolds are "resorbed" by osteoclasts in vitro and in vivo highlights more complex scenarios than predicted from knowledge of physiological bone resorption per se. Investigation of novel biomaterials for bone engineering represents an essential area for the design of tissue engineering strategies.


Assuntos
Materiais Biocompatíveis , Desenvolvimento Ósseo/fisiologia , Substitutos Ósseos , Matriz Extracelular/fisiologia , Engenharia Tecidual/métodos , Biotecnologia/métodos , Remodelação Óssea/fisiologia , Transplante Ósseo/fisiologia , Osso e Ossos/fisiologia , Técnicas de Cultura de Células , Transplante de Células , Humanos , Células-Tronco/fisiologia
15.
Mol Pathol ; 55(1): 58-60, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11836449

RESUMO

In the pituitary gland, activating mutations of the GNAS1 (Gsalpha) gene at Gln227 have been identified in adrenocorticotrophin secreting, growth hormone secreting, and prolactin secreting adenomas. To date, mutations at the codon encoding R201, typically underlying the McCune-Albright syndrome and isolated fibrous dysplasia of bone, have been demonstrated only in growth hormone secreting pituitary adenomas. In this study, a polymerase chain reaction amplified target sequence in exon 8 of the GNAS1 gene was sequenced, identifying the first R201 mutation seen in an isolated basophilic adenoma which generated Cushing's disease in a child. This case adds Cushing's disease to the range of human diseases caused by R201 mutations of the GNAS1 gene.


Assuntos
Adenoma Basófilo/genética , Síndrome de Cushing/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Mutação de Sentido Incorreto , Neoplasias Hipofisárias/genética , Criança , Análise Mutacional de DNA , Feminino , Humanos , Proteínas Oncogênicas/genética
17.
Arch Pathol Lab Med ; 125(10): 1375-8, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11570921

RESUMO

Achondrogenesis type IB is a lethal osteochondrodysplasia caused by mutations in the diastrophic dysplasia sulfate transporter gene. How these mutations lead to the skeletal phenotype is not known. Histology of plastic-embedded skeletal fetal achondrogenesis type IB samples suggested that interterritorial epiphyseal cartilage matrix was selectively missing. Cartilage was organized in "chondrons" separated by cleft spaces; chondrocyte seriation, longitudinal septa, and, in turn, mineralized cartilaginous septa were absent. Agenesis of interterritorial matrix as the key histologic change was confirmed by immunohistology using specific markers of territorial and interterritorial matrix. Biglycan-enriched territorial matrix was preserved; decorin-enriched interterritorial areas were absent, although immunostaining was observed within chondrocytes. Thus, in achondrogenesis type IB: (1) a complex derangement in cartilage matrix assembly lies downstream of the deficient sulfate transporter activity; (2) the severely impaired decorin deposition participates in the changes in matrix organization with lack of development of normal interterritorial matrix; and (3) this change determines the lack of the necessary structural substrate for proper endochondral bone formation and explains the severe skeletal phenotype.


Assuntos
Osso e Ossos/embriologia , Cartilagem/patologia , Doenças Fetais/patologia , Osteocondrodisplasias/genética , Osteocondrodisplasias/patologia , Adulto , Proteínas de Transporte de Ânions , Proteínas de Transporte/genética , Condrócitos/patologia , Consanguinidade , Decorina , Matriz Extracelular/patologia , Proteínas da Matriz Extracelular , Feminino , Idade Gestacional , Lâmina de Crescimento/patologia , Humanos , Masculino , Proteínas de Membrana Transportadoras , Gravidez , Proteoglicanas/análise , Transportadores de Sulfato , Ultrassonografia Pré-Natal
18.
J Bone Miner Res ; 16(9): 1710-8, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11547842

RESUMO

We report an unusual generalized skeletal syndrome characterized by fibro-osseous lesions of the jawbones with a prominent psammomatoid body component, bone fragility, and bowing/sclerosis of tubular bones. The case fits with the emerging profile of a distinct syndrome with similarities to previously reported cases, some with an autosomal dominant inheritance and others sporadic. We suggest that the syndrome be named gnathodiaphyseal dysplasia. The patient had been diagnosed previously with polyostotic fibrous dysplasia (PFD) elsewhere, but further clinical evaluation, histopathological study, and mutation analysis excluded this diagnosis. In addition to providing a novel observation of an as yet poorly characterized syndrome, the case illustrates the need for stringent diagnostic criteria for FD. The jaw lesions showed fibro-osseous features with the histopathological characteristics of cemento-ossifying fibroma, psammomatoid variant. This case emphasizes that the boundaries between genuine GNAS1 mutation-positive FD and other fibro-osseous lesions occurring in the jawbones should be kept sharply defined, contrary to a prevailing tendency in the literature. A detailed pathological study revealed previously unreported features of cemento-ossifying fibroma, including the participation of myofibroblasts and the occurrence of psammomatoid bodies and aberrant mineralization, within the walls of blood vessels. Transplantation of stromal cells grown from the lesion into immunocompromised mice resulted in a close mimicry of the native lesion, including the sporadic formation of psammomatoid bodies, suggesting an intrinsic abnormality of bone-forming cells.


Assuntos
Síndrome de Camurati-Engelmann/patologia , Cementoma/patologia , Fibroma Ossificante/patologia , Displasia Fibrosa Poliostótica/patologia , Neoplasias Maxilomandibulares/patologia , Arcada Osseodentária/patologia , Animais , Síndrome de Camurati-Engelmann/diagnóstico por imagem , Síndrome de Camurati-Engelmann/genética , Síndrome de Camurati-Engelmann/fisiopatologia , Cementoma/diagnóstico por imagem , Cementoma/genética , Cementoma/fisiopatologia , Pré-Escolar , Análise Mutacional de DNA , Fibroma Ossificante/diagnóstico por imagem , Fibroma Ossificante/genética , Fibroma Ossificante/fisiopatologia , Displasia Fibrosa Poliostótica/diagnóstico por imagem , Displasia Fibrosa Poliostótica/genética , Displasia Fibrosa Poliostótica/fisiopatologia , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Arcada Osseodentária/fisiopatologia , Neoplasias Maxilomandibulares/diagnóstico por imagem , Neoplasias Maxilomandibulares/genética , Neoplasias Maxilomandibulares/fisiopatologia , Masculino , Camundongos , Radiografia , Síndrome
19.
Recenti Prog Med ; 92(4): 251-6, 2001 Apr.
Artigo em Italiano | MEDLINE | ID: mdl-11388042

RESUMO

We witness an unprecedented explosion of knowledge and interest in the field of stem cells and stem cell-dependent organ systems. The notion of stem cell has expanded to encompass cells with different properties but all amenable to ex vivo manipulation. We have learned that not only rapidly self-renewing tissues, but also unsuspected systems such as the central nervous system are associated with post-natal progenitor cells. The bone marrow seems to represent an important cross-road of many different progenitors, and perhaps the easiest source of diverse progenitors to be used for therapeutic purposes in a large spectrum of diseases. While some applicative uses of post-natal progenitor cells are either already in use, or soon to be routinely implemented, much larger perspectives are linked to the design of appropriate strategies for cell delivery and stable cell transduction. Meanwhile, major gains in understanding of the biology of different diseases are implied by the very recognition that many diseases are indeed stem cell diseases.


Assuntos
Células-Tronco/fisiologia , Medula Óssea/fisiologia , Previsões , Humanos , Regeneração
20.
Stem Cells ; 19(3): 180-92, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11359943

RESUMO

Bone marrow stromal cells are progenitors of skeletal tissue components such as bone, cartilage, the hematopoiesis-supporting stroma, and adipocytes. In addition, they may be experimentally induced to undergo unorthodox differentiation, possibly forming neural and myogenic cells. As such, they represent an important paradigm of post-natal nonhematopoietic stem cells, and an easy source for potential therapeutic use. Along with an overview of the basics of their biology, we discuss here their potential nature as components of the vascular wall, and the prospects for their use in local and systemic transplantation and gene therapy.


Assuntos
Células da Medula Óssea/metabolismo , Células da Medula Óssea/fisiologia , Células-Tronco/metabolismo , Células-Tronco/fisiologia , Animais , Células da Medula Óssea/ultraestrutura , Transplante de Medula Óssea , Fibroblastos/metabolismo , Técnicas de Transferência de Genes , Terapia Genética , Humanos , Camundongos , Timo/metabolismo
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