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Osteopetrose maligna: transplante de medula óssea; Malignant osteopetrosis: bone marrow transplantation

BORSATO, Maria L.; CASTRO, Helaine C.; PIZZA, Maria; SILVA, Helena R. M.; LUPORINI, Silvia M.; TANAKA, Paula Y.; CASTRO, Nelson S.; BRUNIERA, Paula; BARROS, José C. A.
Fonte: Associação Brasileira de Hematologia e Hemoterapia e daSociedade Brasileira de Transplante de Medula Óssea Publicador: Associação Brasileira de Hematologia e Hemoterapia e daSociedade Brasileira de Transplante de Medula Óssea
Tipo: Artigo de Revista Científica
POR
Relevância na Pesquisa
66.42%
A osteopetrose é uma osteopatia hereditária caracterizada pela deficiência na reabsorção óssea que ocorre por disfunção dos osteoclastos. Com o acúmulo de material osteóide que oblitera o canal medular, ocorre hematopoiese extramedular (hepato-esplenomegalia), obliteração dos forames dos nervos cranianos (cegueira, surdez, paralisias faciais), macrocefalia, protusão da fronte, hipertelorismo, exoftalmo, aumento da pressão intracraniana, retardo na erupção dentária, atraso no crescimento, atraso no desenvolvimento neuropsicomotor, e a morte ocorre precocemente nos primeiros anos de vida. A única alternativa terapêutica curativa é o transplante de medula óssea (TMO) de doador HLA idêntico, pois restabelece a hematopoiese e a função monócito-macrófago, com melhora das lesões ósseas e anormalidades hematopoiéticas, embora não reverta as alterações sensoriais já instaladas. Os autores relatam casos de duas crianças portadoras de osteopetrose maligna submetidas ao transplante de medula óssea com sucesso. A primeira encontra-se no dia +1260 do TMO, com melhora evidente da radiologia esquelética, sem progressão das deficiências neurológicas que apresentava, e com biópsia óssea sem sinais de osteopetrose. O segundo paciente encontra-se no dia + 700...

Study of lymphocyte subpopulations in bone marrow in a model of protein-energy malnutrition

Fock, Ricardo Ambrosio; BLATT, Solange Lucia; BEUTLER, Beatriz; PEREIRA, Juliana; TSUJITA, Maristela; BARROS, Francisco Erivaldo Vidal de; BORELLI, Primavera
Fonte: ELSEVIER SCIENCE INC Publicador: ELSEVIER SCIENCE INC
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
66.43%
Objective: Protein-energy malnutrition (PEM) is an important public health problem affecting millions of people worldwide. Hematopoietic tissue requires a high nutrient supply, and a reduction in leukocytes, especially lymphocytes, suggests that some nutritional deficiencies might be altering bone marrow function and decreasing its ability to produce lymphocytes. In this study, we evaluated the effect that PEM has on lymphocyte subtypes and the cell cycle of CD5(+) cells. Methods: Swiss mice were subjected to PEM using a low-protein diet containing 4% protein. When the experimental group had lost about 20% of their original body weight, we collected blood and bone marrow cells and evaluated the hemogram, the myelogram, bone marrow lymphoid markers using flow cytometry, and the cell cycle in CD5(+) bone marrow. Results: Malnourished animals presented anemia, reticulocytopenia, and leukopenia with lymphopenia. The bone marrow was hypocellular, and flow cytometric analyses of bone marrow cells showed cells that were CD45(+) (91.2%), CD2(+) (84.9%), CD5(+) (37.3%), CD3(+) (23.5%), CD19(+) (43.3%), CD22(+) (34.7%), CD19(+)/CD2(+) (51.2%), CD19(+)/CD3(+)(24.0%), CD19(+)/CD5(+) (13.2%), CD22(+)/CD2(+) (40.1%), CD22(+)/CD3(+) (30.3%), and CD22(+)/CD5(+) (1.1%) in malnourished animals and CD45(+) (97.5%)...

Expression of heterochromatin protein 1 in the primary tumor of breast cancer patients in the presence or absence of occult metastatic cells in the bone marrow

ABREU, A. P. S.; MILANI, C.; KATAYAMA, M. L. H.; BARBOSA, E. M.; FONSECA, L. Gomes da; GOES, I. C. S.; BRENTANI, M. M.; FOLGUEIRA, M. A. A. Koike
Fonte: WICHTIG EDITORE Publicador: WICHTIG EDITORE
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
66.45%
Gene silencing may occur in breast cancer samples from patients presenting with occult metastatic cells in the bone marrow and one mechanism regulating gene suppression is heterochromatin formation. We have studied whether members of the heterochromatin protein 1 family Hp1(Hs alpha), Hp1(Hs beta) and Hp1(Hs gamma) which take part in chromatin packaging and gene expression regulation, were differentially expressed in tumors from patients with and without occult metastatic cells in their bone marrow. Tumor samples and bone marrow aspirates were obtained from 37 breast cancer patients. Median age was 63 years and 68% of the patients presented with clinical stage I/II disease. Presence of occult metastatic cells in bone marrow was detected through keratin-19 expression by nested RT-PCR in samples from 20 patients (54.1%). The presence of occult metastatic cells in bone marrow was not associated with node involvement, histological grade, estrogen receptor and ERBB2 immunoexpression. Relative gene expression of HP1(Hs alpha), HP1(Hs beta) and HP1(Hs gamma) was determined by real-time RT-PCR and did not vary according to the presence of occult metastatic cells in bone marrow. In addition, the combined expression of these three transcripts could not be used to classify samples according to the presence of bone marrow micrometastasis. Our work indicates that regulation of heterochromatin formation through HP1 family members may not be the sole mechanism implicated in the metastatic process to the bone marrow. (Int J Biol Markers 2008; 23: 219-24)

The effect of bone allografts combined with bone marrow stromal cells on the healing of segmental bone defects in a sheep model

Fernandes, Marco Bernardo C.; Guimarães, João Antônio Matheus; Casado, Priscila Ladeira; Cavalcanti, Amanda dos Santos; Gonçalves, Natalia Juliana Nardelli; Ambrosio, Carlos Eduardo; Rodrigues, Fernando; Pinto, Ana Carolina Brandão de Campos Fonseca;
Fonte: BioMed Central Ltd.; Springer Science+Business Media; Londres Publicador: BioMed Central Ltd.; Springer Science+Business Media; Londres
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
66.43%
Background: The repair of large bone defects is a major orthopedic challenge because autologous bone grafts are not available in large amounts and because harvesting is often associated with donor-site morbidity. Considering that bone marrow stromal cells (BMSC) are responsible for the maintenance of bone turnover throughout life, we investigated bone repair at a site of a critically sized segmental defect in sheep tibia treated with BMSCs loaded onto allografts. The defect was created in the mid-portion of the tibial diaphysis of eight adult sheep, and the sheep were treated with ex-vivo expanded autologous BMSCs isolated from marrow aspirates and loaded onto cortical allografts (n = 4). The treated sheep were compared with control sheep that had been treated with cell-free allografts (n = 4) obtained from donors of the same breed as the receptor sheep. Results: The healing response was monitored by radiographs monthly and by computed tomography and histology at six, ten, fourteen, and eighteen weeks after surgery. For the cell-loaded allografts, union was established more rapidly at the interface between the host bone and the allograft, and the healing process was more conspicuous. Remodeling of the allograft was complete at 18 weeks in the cell-treated animals. Histologically...

Avaliação do efeito de centrifugado osteogênico de medula óssea na consolidação de fratura: estudo experimental em coelhos; Effect of centrifuged osteogenic bone-marrow aspirate on bone fracture healing: an experimental study in rabbits

Vaz, Carlos Eduardo Sanches
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 27/06/2006 PT
Relevância na Pesquisa
66.47%
INTRODUÇÃO: O objetivo deste estudo foi de avaliar a eficácia de um centrifugado osteogênico de medula óssea para estimular a consolidação de osteotomias da fíbula em coelhos. MÉTODOS: Este estudo experimental envolveu a utilização de dez coelhos machos adultos da raça Nova Zelândia albino. Realizou-se uma osteotomia transversa médio-diafisária da fíbula direita, seguida da adição local de uma esponja de colágeno absorvível embebida em um centrifugado osteogênico, obtido pela centrifugação de aspirado de medula óssea do osso ilíaco ipsilateral. A fíbula esquerda foi utilizada como controle, sendo feita a mesma osteotomia, porém neste caso adicionando-se somente a esponja de colágeno absorvível. O centrifugado de medula óssea elaborado em laboratório foi submetido à contagem do número de células nucleadas e a teste de viabilidade celular antes de ser administrada no local das osteotomias. Após quatro semanas os animais foram sacrificados para estudo dos calos ósseos formados. Os critérios de avaliação foram a mensuração da densidade mineral utilizando-se a densitometria óssea com DEXA, do volume do calo com tomografia computadorizada multi-slice e dos tecidos formados por meio de histomorfometria. RESULTADOS: O método utilizado para a centrifugação dos aspirados de medula óssea resultou em uma concentração média de células nucleadas três vezes maior que o número destas células nos aspirados originais...

Expressão gênica diferencial das células estromais obtidas de medula óssea na presença ou ausência de célula tumoral oculta em pacientes com câncer de mama; Differential gene expression of bone marrow stromal cells from breast cancer patients in the presence or abscence of occult tumor cells

Milani, Cintia
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 21/09/2006 PT
Relevância na Pesquisa
66.45%
A célula estromal pode influenciar o desenvolvimento do tumor no sítio primário e secundário, mas pouco é conhecido sobre as características moleculares das células estromais presentes na medula óssea de pacientes com câncer de mama. Nosso objetivo foi avaliar a expressão gênica diferencial entre as células estromais oriundas de medula óssea na presença ou ausência de célula tumoral oculta. Coletamos dez aspirados de medula óssea das pacientes com câncer de mama. A classificação do comprometimento da medula por células tumorais ocultas foi realizada pela detecção da expressão de CK19 por Nested-RT-PCR e quatro entre dez pacientes apresentaram presença de célula tumoral na medula óssea. Estabelecemos culturas primárias de células estromais de todas as amostras e, selecionamos amostras originárias de duas pacientes contendo linfonodos comprometidos e presença de célula tumoral oculta em medula e também de duas pacientes que não apresentavam linfonodos comprometidos e nem célula tumoral oculta na medula. As pacientes selecionadas eram pós-menopausadas com diagnóstico de carcinoma ductal invasor e expressão imunohistoquímica positiva para receptor de estrógeno e progesterona. Realizamos avaliação do perfil de expressão gênica entre estes dois grupos...

Análise de células mesenquimais de saco vitelino, figado e medula óssea de fetos caninos; Analysis of mesenchymal cells from yolk sac, liver and bone marrow of the canine fetus

Wenceslau, Cristiane Valverde
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 05/02/2010 PT
Relevância na Pesquisa
66.48%
Em vista das limitações éticas em torno da obtenção de células-tronco de fetos humanos, o cão é uma alternativa para estes estudos. Além disso, a terapia celular proporciona novas expectativas para o tratamento na espécie. Realizamos o estudo comparativo das células isoladas de saco vitelino, fígado e medula óssea de fetos caninos. As células foram analisadas microscopicamente e ultra estruturalmente. O imunofenótipo das células foi avaliado através de marcadores. Caracterizamos a plasticidade, o cariótipo e o potencial teratogênico destas células. Após expansão as células progenitoras formaram colônias com morfologia fibroblastóide. As células progenitoras do saco vitelino e medula óssea são compostas por: células com alta proporção núcleo-citoplasma e células com citoplasma rico em organelas, enquanto que as células progenitoras do fígado eram semelhantes à célula epitelial e células ricas em organelas. As células-progenitoras dos três tecidos fetais foram positivas para os anticorpos nestina e vimentina, mas negativas para CD45 e CD13. Células progenitoras de medula óssea foram positivas para o marcador CD44. Células progenitoras do fígado e medula óssea expressaram a proteína citoqueratina-18...

Pesquisa de isoformas da fibronectina em culturas de longa duração de estroma medular de camundongos submetidos à desnutrição proteica; Search fibronectin isoforms in cultures of long-term bone marrow stroma of mice submitted to protein malnutrition

Silva, Graziela Batista da
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 26/09/2011 PT
Relevância na Pesquisa
66.46%
A desnutrição acomete 925 milhões de pessoas em todo o mundo, independentemente da idade e classe social, os mais acometidos são indivíduos hospitalizados, crianças e idosos. A desnutrição causa alterações fisiológicas em diversos tecidos. O tecido hematopoiético é afetado na desnutrição protéica, por ser um tecido de elevada e constante necessidade de proteínas, levando a alterações hematológicas como anemia e leucopenia. Estudos do nosso laboratório têm demonstrado in vivo, alterações do microambiente hematopoiético, em camundongos submetidos à desnutrição protéica, bem como hipoplasia medular, mudanças quantitativas da matriz extracelular (MEC) como o aumento do deposito de fibronectina na região subendosteal (local da fixação das células tronco/ progenitoras hematopoiéticas), alterações do ciclo celular das células tronco/ progenitoras hematopoiéticas e alteração na expressão de VLA5; principal integrina na interação das células a fibronectina. Sendo assim propõe-se neste projeto avaliar possíveis isoformas da molécula de fibronectina, para melhor compreender o seu papel biológico no ciclo celular as células tronco/ progenitoras hematopoiéticas em um modelo de desnutrição protéica. Para isso foram utilizados camundongos C57BLI/6J machos...

Exequibility of differential gene expression analysis by DDRT-PCR in murine bone marrow cells

De Almeida, Danilo C.; Santos, Rodrigo Da S.; Ribeiro-Paes, João T.
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 424-431
ENG
Relevância na Pesquisa
66.47%
Model of study: Experimental study. Introduction: Recently, stem cell research has generated great interest due to its applicability in regenerative medicine. Bone marrow is considered the most important source of adult stem cells and the establishment of new methods towards gene expression analysis regarding stem cells has become necessary. Thus Differential Display Reverse Transcription Polymerase Chain Reaction (DDRT-PCR) may be an accessible tool to investigate small differences in the gene expression of different stem cells in distinct situations. Aim: In the present study, we investigated the exequibility of DDRT-PCR to identify differences in global gene expression of mice bone marrow cells under two conditions. Methods: First, bone marrow cells were isolated fresh and a part was cultivated during one week without medium replacement. Afterwards, both bone marrow cells (fresh and cultivated) were submitted to gene expression analyses by DDRT-PCR. Results: Initially, it was possible to observe in one week-cultured bone marrow cells, changes in morphology (oval cells to fibroblastic-like cells) and protein profile, which was seen through differences in band distribution in SDS-Page gels. Finally through gene expression analysis...

Aspectos moleculares do citomegalovirus humano durante infecção ativa em pacientes submetidos ao transplante de medula ossea; Molecular profile of human cytomegalovirus in bone marrow transplant recipients with active infection

Dulcineia Martins de Albuquerque
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 24/02/2006 PT
Relevância na Pesquisa
66.43%
O Citomegalovírus Humano (HCMV) continua sendo uma causa significante de morbidade em pacientes imunocomprometidos, especialmente em transplantados de medula óssea, e pode manifestar diversas complicações que incluem hepatite, doença gastrointestinal e pneumonia intersticial ou a denominada ?Síndrome Viral por HCMV? caracterizada por febre, leucopenia e trombocitopenia. O HCMV pode também ter um efeito imuno-modulador, fazendo da infecção por esse vírus um fator de risco importante para o desenvolvimento de rejeição ao enxerto aguda e crônica e para co-infecção com outras herpesviroses. A detecção do genoma do HCMV pela PCR (Reação em Cadeia da Polimerase) é específica e sensível, e pode ser usada como uma poderosa ferramenta para o diagnóstico precoce da infecção causada por este vírus. Variações em regiões funcionalmente relevantes do genoma do HCMV têm sido utilizadas como marcadores genéticos em diversos estudos clínicos para diferenciar as linhagens do vírus e associá-las com a patogênese viral e com as manifestações clínicas no paciente. A glicoproteína B (gB) é a maior glicoproteína do envelope do HCMV e tem sido relacionada à entrada na célula hospedeira, transmissão célula-a-célula...

Efeito do tratamento da malaria cerebral com celulas da medula ossea em camundongos infectados pelo Plasmodium berghei ANKA; Effect of tratment of cerebral with bone marrow cells in mice infected by Plasmodium berghei ANKA

Helen Cupertino Silva Pinto
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 26/08/2009 PT
Relevância na Pesquisa
66.48%
A malária cerebral humana é a manifestação mais grave do Plasmodium falciparum que ocorre em 1% das infecções, sendo responsável por mais de dois milhões de mortes anuais entre crianças abaixo de cinco anos. O modelo experimental mais aceito da malária cerebral é o camundongo C57BL/6 infectado pelo Plasmodium berghei ANKA (PbA). A administração da fração mononuclear da medula óssea, contendo principalmente células tronco mesenquimais e hematopoiéticas, constitui uma estratégia promissora no tratamento de danos neurais causados por acidente vascular cerebral. Neste estudo, foi avaliado o efeito de células da medula óssea de camundongos transgênicos C57BL/6 GFP HET transplantadas em C57BL/6JUnib infectados com 106 hemácias parasitadas pelo PbA. Resumidamente, células perfundidas da medula do fêmur e tíbia de C57BL/6 GFP HET foram purificadas por gradiente de Ficoll (Histopaque) a 1000 x g por 15 minutos. Após duas lavagens em meio RPMI, as células foram ressuspensas em NaCl 0,15 M. No segundo dia após a infecção (dai) pelo PbA, foram injetadas 3,0 x 106 a 4,6 x 107 células de medula óssea (CMO) no plexo oftálmico dos camundongos devidamente anestesiados com ketamina/xylasina (protocolo 1078-1 CEEA/Unicamp). Alguns camundongos receberam apenas a injeção de células totais da medula óssea (CTMO)...

Folinic acid attenuates methotrexate chemotherapy-induced damages on bone growth mechanisms and pools of bone marrow stromal cells

Xian, C.; Cool, J.; Scherer, M.; Fan, C.; Foster, B.
Fonte: Wiley-Liss Publicador: Wiley-Liss
Tipo: Artigo de Revista Científica
Publicado em //2008 EN
Relevância na Pesquisa
66.46%
Chemotherapy often induces bone growth defects in pediatric cancer patients; yet the underlying cellular mechanisms remain unclear and currently no preventative treatments are available. Using an acute chemotherapy model in young rats with the commonly used antimetabolite methotrexate (MTX), this study investigated damaging effects of five once-daily MTX injections and potential protective effects of supplementary treatment with antidote folinic acid (FA) on cellular activities in the tibial growth plate, metaphysis, and bone marrow. MTX suppressed proliferation and induced apoptosis of chondrocytes, and reduced collagen-II expression and growth plate thickness. It reduced production of primary spongiosa bone, volume of secondary spongiosa bone, and proliferation of metaphyseal osteoblasts, preosteoblasts and bone marrow stromal cells, with the cellular activities being most severely damaged on day 9 and returning to or towards near normal levels by day 14. On the other hand, proliferation of marrow pericytes was increased early after MTX treatment and during repair. FA supplementation significantly suppressed chondrocyte apoptosis, preserved chondrocyte proliferation and expression of collagen-II, and attenuated damaging effects on production of calcified cartilage and primary bone. The supplementation also significantly reduced MTX effects on proliferation of metaphyseal osteoblastic cells and of bone marrow stromal cells...

Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp

Shi, S.; Gronthos, S.
Fonte: Amer Soc Bone & Mineral Res Publicador: Amer Soc Bone & Mineral Res
Tipo: Artigo de Revista Científica
Publicado em //2003 EN
Relevância na Pesquisa
76.37%
Mesenchymal stem cell populations have previously been identified in adult bone marrow and dental pulp that are capable of regenerating the bone marrow and dental pulp microenvironments, respectively. Here we show that these stem cell populations reside in the microvasculature of their tissue of origin. Human bone marrow stromal stem cells (BMSSCs) and dental pulp stem cells (DPSCs) were isolated by immunoselection using the antibody, STRO-1, which recognizes an antigen on perivascular cells in bone marrow and dental pulp tissue. Freshly isolated STRO-1 positive BMSSCs and DPSCs were tested for expression of vascular antigens known to be expressed by endothelial cells (von Willebrand factor, CD146), smooth muscle cells, and pericytes (-smooth muscle actin, CD146), and a pericyte-associated antigen (3G5), by immunohistochemistry, fluorescence-activated cell sorting (FACS), and/or immunomagnetic bead selection. Both BMSSCs and DPSCs lacked expression of von Willebrand factor but were found to be positive for -smooth muscle actin and CD146. Furthermore, the majority of DPSCs expressed the pericyte marker, 3G5, while only a minor population of BMSSCs were found to be positive for 3G5. The finding that BMSSCs and DPSCs both display phenotypes consistent with different perivascular cell populations...

Damage and recovery of the bone marrow microenvironment induced by cancer chemotherapy - potential regulatory role of chemokine CXCL12/receptor CXCR4 signalling

Georgiou, K.; Foster, B.; Xian, C.
Fonte: Bentham Science Publishers Ltd. Publicador: Bentham Science Publishers Ltd.
Tipo: Artigo de Revista Científica
Publicado em //2010 EN
Relevância na Pesquisa
66.46%
The bone marrow microenvironment houses haematopoietic stem cells (HSC), mesenchymal stem cells (MSC) and their progeny, supports haematopoiesis, osteogenesis, osteoclastogenesis, and adipogenesis. It plays a key role in maintaining homeostatic production of erythroid, myeloid or lymphoid cells, appropriate bone mass and bone health throughout life. Through cell-cell adhesion and chemotactic axes, a reciprocal inter-dependent relationship exists between these two cell lineages. Following chemotherapy-induced myelosuppression observed in cancer patients, HSCs are induced to enter into the cell cycle in order to re-establish the damaged microenvironment. These cells not only have the capacity to mobilize to the peripheral blood, but the ability to repopulate the marrow cavity as required. However, depending on the dosage and length of chemotherapy treatment, complications in bone and bone marrow recovery occur. This may manifest as marrow haematopoietic depletion, high marrow fat content, reduced bone formation and aggravated osteoclastic bone resorption. Although the molecular and cellular mechanisms governing injured states of the marrow microenvironment are yet to be fully elucidated, many reports have demonstrated the CXCL12/CXCR4 axis plays an important role in regulating the two cell lineages. Their interaction maintains bone marrow homeostasis and orchestrates its regeneration following chemotherapy. This review explores movement of MSC and HSC...

Role of Wnt/β-catenin and CXCL12/CXCR4 signalling axes in the damage and recovery of the bone marrow microenvironment following methotrexate chemotherapy.

Georgiou, Kristen Renée
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2011
Relevância na Pesquisa
66.52%
The bone marrow microenvironment is home to mesenchymal and haematopoietic stem cells and their respective progeny. Mesenchymal stem cells are multipotent and have the capacity to differentiate into a number of cell types, namely osteoblasts, adipocytes and chondrocytes. These cells and cells of the haematopoietic lineage maintain close interactions within the marrow cavity and are responsible for bone and bone marrow maintenance throughout life. Disruptions to cell populations and steady-state interactions within the bone marrow such as that seen following cancer chemotherapy treatment are associated with bone-related complications in later life such as osteoporosis. However, the underlying mechanisms of these defects and the subsequent recovery potential remain unclear. The studies presented herein have investigated the effects of the commonly used antimetabolite methotrexate (MTX) on the damage and recovery of the bone marrow microenvironment and potential signalling pathways involved, focusing on Wnt/β-catenin and CXCL12/CXCR4 signalling axes. Using a short-term rat MTX model of 5 consecutive daily doses at 0.75mg/kg, histological techniques were employed to assess bone/fat formation and cell culture techniques were used to investigate differentiation potential of bone marrow mesenchymal and haematopoietic cells. These investigations were further supported by protein expression and quantitative RT-PCR analyses of associated genes over the MTX timecourse. The bone marrow cavity was observed to undergo a number of changes when assessed histologically...

Reaktive und neoplastische T-Zellen im menschlichen Knochenmark - Immunhistochemische und morphometrische Untersuchungen mit den monoklonalen Antikörpern gegen die Antigene CD5 und CD8; Reactive and neoplastic T-Lymphocytes in human bone marrow - morphological and immunohistochemical investigations using the monoclonal antibodies Anti-CD5 and Anti-CD8

Jüngst, Cornelia
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
DE_DE
Relevância na Pesquisa
66.43%
Es wurden 86 formalinfixierte, in EDTA entkalkte und in Paraffin eingebettete Beckenkammtrepanate von 9 hämatologisch gesunden Kontrollpersonen, 5 Patienten mit histologisch gesichertem B-NHL, 5 Patienten mit T-NHL und 67 Patienten mit Lymphozytosen unklarer Dignität (LUD) untersucht, davon 19 mit monoklonalem und 48 mit polyklonalem Befund in der PCR. Die Schnittpräparate wurden immunhistochemisch mit monoklonalen Antikörpern gegen CD5 und gegen CD8 untersucht und der prozentuale Anteil CD5+ bzw. CD8+ Zellen bezogen auf 100 kernhaltige Markzellen ermittelt. Dieser wurde zu den Ergebnissen für CD3+ und CD20+ Lymphozyten aus vorhergegangenen Studien (Dissertationen Dauenhauer und Küßwetter, 2001) in Beziehung gesetzt. Als wesentliche Befunde konnten wir in der Gruppe der hämatologisch Gesunden einen Anteil von 2,0% für CD5+ Zellen und von 2,1% für CD8+ Zellen feststellen. In der Gruppe der B-NHL wurden CD5+ B-Zellen durch den Antikörper schlecht erfasst. Insgesamt waren die CD5+ Lymphozyten gegenüber der Kontrollgruppe um etwa 30% erhöht. Der Anteil CD8+ Lymphozyten an der Gesamtzahl der T-Lymphozyten war deutlich geringer ist als im normalen Knochenmark. Bei den T-NHL wurde im fokalen Infiltrat mit 32,5% CD5+ Zellen erwartungsgemäß eine starke Erhöhung gegenüber der Kontrollgruppe beobachtet. CD8+ Zellen machten nur etwa 1/8 dieses Anteils aus. Im diffusen Infiltrat war der Anteil der CD8+ Zellen mit 3...

Histopathologische und biologische Prognosefaktoren für den immunzytologischen Nachweis von Tumorzellen im Knochenmark beim Mammakarzinom; Histopathological and biological prognosis factors for the immunocytological detection of tumor cells in the bone marrow in mamma carcinoma

Nurali, Ihsan
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
DE_DE
Relevância na Pesquisa
66.43%
Das Mammakarzinom stellt bei vielen Erkrankten bereits zum Zeitpunkt der Diagnose eine systemische Erkrankung dar, deshalb bleiben selbst nodalnegative Patienten von einem späteren Fernrezidiv nicht verschont. Diese Patienten im T1N0M0-Stadium haben eigentlich eine sehr gute Überlebensprognose und bedürfen nicht in jedem Fall einer adjuvanten Therapie, jedoch eine kleine Subgruppe diesen Kollektives entwickelt ein Rezidiv. Eine frühzeitige hämatogene, evtl. lymphogene Tumorzelldissemination scheint dabei eine herausragende Rolle einzunehmen. Diese “Fremdzellen“ können im Knochenmark als geeignetem Kompartiment durch Immunzytologie und FISH analysiert werden. Gegenstand dieser Arbeit war zu überprüfen ob histopathologische und biologische Prognosefaktoren eine Auskunft über den Istzustand des Knochenmarks [KM] bezüglich eines Tumorzellbefalles geben können und ob bzw. inwieweit klassische adjuvante Behandlungsmaßnahmen einen Einfluß auf die Anzahl zytokeratin- positiver Zellen im Knochenmark haben. Die Untersuchung des KM-Status als möglicher neuer prognostischer und prädiktiver Faktor soll dazu beitragen, zusätzliche Informationen über das jeweilige Patientenrisiko zu erhalten um insbesondere bei nodalnegativen Brustkrebserkrankten effektivere individuelle Therapieentscheidungen zu treffen. In unserer Untersuchung wurden retrospektiv die Daten von 310 Patientinnen...

Influence of bone marrow on osseointegration in long bones: an experimental study in sheep

Morelli, Fabrizio; Lang, Niklaus P.; Bengazi, Franco; Baffone, Davide; Dadonim Vila Morales, C.; Botticelli, Daniele
Fonte: Wiley-Blackwell Publicador: Wiley-Blackwell
Tipo: Artigo de Revista Científica Formato: 300-306
ENG
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Aim To evaluate the influence of yellow bone marrow on osseointegration of titanium oral implants using a long bone model.Material and methodsThe two tibiae of eight sheep were used as experimental sites. Two osteotomies for implant installation were prepared in each tibia. At the control sites, no further treatments were performed while, at the test sites, bone marrow was removed from the osteotomy site with a curette to an extent that exceeded the implant dimensions. As a result, the apical portion of the implants at the control sites was in contact with bone marrow while, at the test sites, it was in contact with the blood clot. After 2months, the same procedures were performed in the contralateral side. After another month, the animal was sacrificed. Ground sections were obtained for histological analysis.ResultsAfter 1month of healing, no differences between test and control sites were found in the apical extension of osseointegration and the percentage of new bone-to-implant contact. However, after 3months of healing, a higher percentage of new bone-to-implant contact was found at the test compared to the control sites in the marrow compartment. The apical extension of osseointegration, however, was similar to that found at the 1-month healing period both for test and control sites.ConclusionsOsseointegration appeared to be favored by the presence of a blood clot when compared to the presence of yellow fatty bone marrow. Moreover...

Concentration of Adipogenic and Proinflammatory Cytokines in the Bone Marrow Supernatant Fluid of Osteoporotic Women

Fernández, Mireya; Rodríguez, J. Pablo; Figueroa, Paula; Seitz, Germán; Astudillo, Pablo; Ríos, Susana; Pino, Ana María
Fonte: Universidade do Chile Publicador: Universidade do Chile
Tipo: Artículo de revista
EN
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Osteoporosis is characterized by low bone mass, microarchitectural deterioration of bone tissue leading to increased bone fragility, and a resulting susceptibility to fractures. Distinctive environmental bone marrow conditions appear to support the development and maintenance of the unbalance between bone resorption and bone formation; these complex bone marrow circumstances would be reflected in the fluid surrounding bone marrow cells. The content of regulatory molecules in the extracellular fluid from the human bone marrow is practically unknown. Since the content of cytokines such as adiponectin, leptin, osteoprogeterin (OPG), soluble receptor activator of nuclear factor kB ligand (s-RANKL), tumor necrosis factor a, and interleukin 6 (IL-6) may elicit conditions promoting or sustaining osteoporosis, in this work we compared the concentrations of the above-mentioned cytokines and also the level of the soluble receptors for both IL-6 and leptin in the extracellular fluid from the bone marrow of nonosteoporotic and osteoporotic human donors. A supernatant fluid (bone marrow supernatant fluid [BMSF]) was obtained after spinning the aspirated bone marrow samples; donors were classified as nonosteoporotic or osteoporotic after dual-energy X-ray absorptiometry (DXA) measuring. Specific commercially available kits were used for all measurements. The cytokines’ concentration in BMSF showed differently among nonosteoporotic and osteoporotic women; this last group was characterized by higher content of proinflammatory and adipogenic cytokines. Also...

Exequibilidade do DDRT-PCR para análise da expressão gênica diferencial em células de medula óssea murina; Exequibility of differential gene expression analysis by DDRT-PCR in murine bone marrow cells

Almeida, Danilo C. de; Santos, Rodrigo da S.; Ribeiro-Paes, João T.
Fonte: Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto Publicador: Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; Formato: application/pdf
Publicado em 30/12/2012 ENG
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Model of study: Experimental study. Introduction: Recently, stem cell research has generated greatinterest due to its applicability in regenerative medicine. Bone marrow is considered the most importantsource of adult stem cells and the establishment of new methods towards gene expression analysisregarding stem cells has become necessary. Thus Differential Display Reverse Transcription Polymerase Chain Reaction (DDRT-PCR) may be an accessible tool to investigate small differences in the geneexpression of different stem cells in distinct situations.Aim: In the present study, we investigated the exequibility of DDRT-PCR to identify differences in globalgene expression of mice bone marrow cells under two conditions.Methods: First, bone marrow cells were isolated fresh and a part was cultivated during one week withoutmedium replacement. Afterwards, both bone marrow cells (fresh and cultivated) were submitted to geneexpression analyses by DDRT-PCR.Results: Initially, it was possible to observe in one week-cultured bone marrow cells, changes in morphology (oval cells to fibroblastic-like cells) and protein profile, which was seen through differences inband distribution in SDS-Page gels. Finally through gene expression analysis, we detected three bands(1300...