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2.
Development ; 128(13): 2525-36, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11493569

RESUMO

Fox factors (winged-helix transcription factors) play important roles in early embryonic patterning. We show here that FoxD3 (Forkhead 6) regulates neural crest determination in Xenopus embryos. Expression of FoxD3 in the presumptive neural crest region starts at the late gastrula stage in a manner similar to that of Slug, and overlaps with that of Zic-r1. When overexpressed in the embryo and in ectodermal explants, FoxD3 induces expression of neural crest markers. Attenuation of FoxD3-related signaling by a dominant-negative FoxD3 construct (FoxD3delN) inhibits neural crest differentiation in vivo without suppressing the CNS marker Sox2. Interestingly, these loss-of-function phenotypes are reversed by coinjecting SLUG: In animal cap explants, neural crest differentiation induced by Slug and Wnt3a is also inhibited by FoxD3delN but not by a dominant-negative form of XBF2. Loss-of-function studies using dominant-negative forms of FoxD3 and Slug indicate that Slug induction by Zic factors requires FoxD3-related signaling, and that FoxD3 and Slug have different requirements in inducing downstream neural crest markers. These data demonstrate that FoxD3 (or its closely related factor) is an essential upstream regulator of neural crest determination.


Assuntos
Crista Neural/embriologia , Proteínas Repressoras/metabolismo , Transdução de Sinais , Proteínas de Xenopus , Animais , Biomarcadores , Proteína Morfogenética Óssea 4 , Proteínas Morfogenéticas Ósseas/metabolismo , Diferenciação Celular , Proteínas de Ligação a DNA/metabolismo , Ectoderma , Fatores de Transcrição Forkhead , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Proteínas do Tecido Nervoso/metabolismo , Proteínas Repressoras/genética , Fatores de Transcrição da Família Snail , Fatores de Transcrição/metabolismo , Xenopus laevis/embriologia , Xenopus laevis/metabolismo
3.
Intern Med ; 40(1): 18-22, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11201363

RESUMO

A 54-year-old man with a complaint of dysphagia was found to have a prominent stricture in the proximal esophagus. A biopsy of the stenotic area indicated sarcoma, leading to subtotal esophagectomy. The surgically removed esophagus demonstrated a well-defined intramural mass, consisting of a mixture of fibroblastic cells with bland cytological appearances and inflammatory cells. Reflux esophagitis which was present distal to the stricture seemed to play a role in the development of this inflammatory pseudotumor.


Assuntos
Doenças do Esôfago/diagnóstico , Neoplasias Esofágicas/diagnóstico , Granuloma de Células Plasmáticas/diagnóstico , Adulto , Idoso , Bário , Colo/transplante , Transtornos de Deglutição/etiologia , Diagnóstico Diferencial , Doenças do Esôfago/complicações , Doenças do Esôfago/diagnóstico por imagem , Doenças do Esôfago/patologia , Doenças do Esôfago/cirurgia , Estenose Esofágica/diagnóstico por imagem , Estenose Esofágica/etiologia , Estenose Esofágica/cirurgia , Esofagectomia , Esofagite Péptica/complicações , Esofagoplastia , Esofagoscopia , Tecido de Granulação/patologia , Granuloma de Células Plasmáticas/diagnóstico por imagem , Granuloma de Células Plasmáticas/patologia , Granuloma de Células Plasmáticas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/etiologia , Radiografia , Sarcoma/diagnóstico , Transplante Heterotópico
4.
Neuron ; 28(1): 31-40, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11086981

RESUMO

We have identified a stromal cell-derived inducing activity (SDIA) that promotes neural differentiation of mouse ES cells. SDIA accumulates on the surface of PA6 stromal cells and induces efficient neuronal differentiation of cocultured ES cells in serum-free conditions without use of either retinoic acid or embryoid bodies. BMP4, which acts as an antineuralizing morphogen in Xenopus, suppresses SDIA-induced neuralization and promotes epidermal differentiation. A high proportion of tyrosine hydroxylase-positive neurons producing dopamine are obtained from SDIA-treated ES cells. When transplanted, SDIA-induced dopaminergic neurons integrate into the mouse striatum and remain positive for tyrosine hydroxylase expression. Neural induction by SDIA provides a new powerful tool for both basic neuroscience research and therapeutic applications.


Assuntos
Antígenos de Diferenciação/metabolismo , Dopamina/metabolismo , Mesencéfalo/metabolismo , Neurônios/metabolismo , Células Estromais/metabolismo , Animais , Antígenos de Diferenciação/farmacologia , Proteína Morfogenética Óssea 4 , Proteínas Morfogenéticas Ósseas/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Corpo Estriado/citologia , Corpo Estriado/metabolismo , Corpo Estriado/cirurgia , Meios de Cultura Livres de Soro/farmacologia , Técnicas de Cultura/métodos , Células Epidérmicas , Epiderme/efeitos dos fármacos , Mesencéfalo/citologia , Mesencéfalo/cirurgia , Camundongos , Camundongos Endogâmicos , Neurônios/citologia , Neurônios/transplante , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células Estromais/citologia , Tirosina 3-Mono-Oxigenase/metabolismo , Proteínas de Xenopus
5.
Proc Natl Acad Sci U S A ; 97(10): 5291-6, 2000 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-10779551

RESUMO

The midline tissues are important inductive centers of early vertebrate embryos. By signal peptide selection screening, we isolated a secreted factor, Kielin, which contains multiple cys-rich repeats similar to those in chordin (Chd). Expression of Kielin starts at midgastrula stages in the notochord and is detected in the floor plate of neurula embryos. Kielin is induced in mesoderm and in ectoderm by nodal-related genes. Chd is sufficient to activate Kielin expression in mesoderm whereas Shh or HNF-3beta in addition to Chd is required for induction in ectoderm. Kielin has a distinct biological activity from that of Chd. Injection of Kielin mRNA causes dorsalization of ventral marginal zone explants and expansion of MyoD expression in neurula embryos. Unlike Chd, Kielin does not efficiently induce neural differentiation of animal cap ectoderm, suggesting that the activity of Kielin is not simply caused by BMP4 blockade. Kielin is a signaling molecule that mediates inductive activities of the embryonic midline.


Assuntos
Padronização Corporal , Embrião não Mamífero/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Glicoproteínas , Substâncias de Crescimento/química , Substâncias de Crescimento/genética , Peptídeos e Proteínas de Sinalização Intercelular , Proteínas de Xenopus , Xenopus/embriologia , Sequência de Aminoácidos , Animais , Mesoderma/fisiologia , Dados de Sequência Molecular , Proteína MyoD/genética , Técnicas de Cultura de Órgãos , Proteínas/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sequências Repetitivas de Aminoácidos , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transdução de Sinais
6.
Mech Dev ; 91(1-2): 81-9, 2000 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-10704833

RESUMO

We report a novel zygotic gene encoding a Xenopus endodermal nuclear factor, Xenf. Expression of Xenf starts at the late blastula stages and is decreased after gastrulation. Xenf shows no structural homology to any known proteins. When GFP-tagged Xenf is overexpressed in Xenopus cells, Xenf protein is localized to the nucleus, associating closely with the chromosomes. In animal cap assays, Xenf expression is strongly activated by mRNA injection of Vg1 and VegT, maternal vegetal genes that can induce endodermal differentiation. In contrast, Xenf is not induced by endoderm-inducing zygotic transcription factors such as Sox17 and Mix-related genes. In turn, Xenf does not activate expression of Sox17, Mixer or Milk. Thus, Xenf is regulated by maternal vegetal positional information in a parallel manner to Sox17 and Mix-related gene pathways.


Assuntos
Proteínas de Ligação a DNA , Glicoproteínas/metabolismo , Proteínas de Grupo de Alta Mobilidade , Proteínas de Homeodomínio/metabolismo , Proteínas Nucleares/metabolismo , Peptídeo Sintases , Proteínas/metabolismo , Proteínas de Répteis , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases , Proteínas de Xenopus , Sequência de Aminoácidos , Animais , Sequência de Bases , Biomarcadores , DNA Complementar , Endoderma , Regulação da Expressão Gênica no Desenvolvimento , Glicoproteínas/genética , Proteínas de Homeodomínio/genética , Dados de Sequência Molecular , Proteínas Nucleares/genética , Proteínas/genética , RNA Mensageiro , Fatores de Transcrição SOXF , Frações Subcelulares , Proteínas com Domínio T/genética , Distribuição Tecidual , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta , Xenopus laevis/embriologia , Xenopus laevis/metabolismo , Zigoto
7.
Development ; 127(4): 791-800, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10648237

RESUMO

From early stages of development, Sox2-class transcription factors (Sox1, Sox2 and Sox3) are expressed in neural tissues and sensory epithelia. In this report, we show that Sox2 function is required for neural differentiation of early Xenopus ectoderm. Microinjection of dominant-negative forms of Sox2 (dnSox2) mRNA inhibits neural differentiation of animal caps caused by attenuation of BMP signals. Expression of dnSox2 in developing embryos suppresses expression of N-CAM and regional neural markers. We have analyzed temporal requirement of Sox2-mediated signaling by using an inducible dnSox2 construct fused to the ligand-binding domain of the glucocorticoid receptor. Attenuation of Sox2 function both from the late blastula stage and from the late gastrula stage onwards causes an inhibition of neural differentiation in animal caps and in whole embryos. Additionally, dnSox2-injected cells that fail to differentiate into neural tissues are not able to adopt epidermal cell fate. These data suggest that Sox2-class genes are essential for early neuroectoderm cells to consolidate their neural identity during secondary steps of neural differentiation.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Sistema Nervoso/embriologia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Xenopus/embriologia , Xenopus/genética , Animais , Padronização Corporal/genética , Ectoderma/citologia , Feminino , Marcadores Genéticos , Proteínas HMGB , Masculino , Fatores de Transcrição SOXB1 , Transdução de Sinais , Xenopus/metabolismo , Proteínas de Xenopus
8.
Artigo em Inglês | MEDLINE | ID: mdl-10052379

RESUMO

A case of benign solitary fibrous tumor of the oral cavity is reported. The tumor occurred in the buccal mucosa of a 34-year-old woman. The surgically removed tumor was 1.5 x 1.2 x 1.0 cm in size and well circumscribed. Histologically, the tumor was composed of spindle-shaped cells that were predominantly arranged haphazardly. Hemangiopericytoma-like areas and collagenous areas were also noted. Immunohistochemically, the tumor cells were positive for CD34 and vimentin. To our knowledge, this is only the second report of solitary fibrous tumor involving the oral cavity.


Assuntos
Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Neoplasias de Tecido Fibroso/patologia , Adulto , Antígenos CD34/análise , Antígenos de Neoplasias/análise , Feminino , Histocitoquímica , Humanos , Neoplasias Bucais/química , Neoplasias de Tecido Fibroso/química , Vimentina/análise
9.
Neuron ; 21(1): 77-85, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9697853

RESUMO

Vertebrate neurogenesis is initiated by the organizer factors that inhibit antineuralizing activities of bone morphogenetic proteins (BMPs) in the ectoderm. Here, we report a candidate mediator of neuralization, SoxD. Expression of SoxD starts at late blastula stages widely in the prospective ectoderm and becomes restricted to the dorsal ectoderm by mid-gastrula stages. SoxD expression is enhanced by the neural inducer Chordin and is suppressed by BMP4 and its downstream genes. Microinjection of SoxD mRNA causes ectopic formation of neural tissues in vivo and induces neural and neuronal markers in the isolated animal cap. Injection of a dominant-negative form of SoxD mRNA can block neuralization of ectoderm caused by attenuation of BMP signals and can strongly suppress formation of anterior neural tissues in vivo. These data show that SoxD functions as an essential mediator of downstream signaling of neural induction.


Assuntos
Proteínas de Bactérias , Grupo dos Citocromos c/fisiologia , Tecido Nervoso/embriologia , Xenopus/embriologia , Sequência de Aminoácidos , Animais , Proteínas Morfogenéticas Ósseas/fisiologia , Grupo dos Citocromos c/genética , Grupo dos Citocromos c/farmacologia , Ectoderma/citologia , Ectoderma/efeitos dos fármacos , Embrião não Mamífero/fisiologia , Expressão Gênica/fisiologia , Dados de Sequência Molecular , Transdução de Sinais/fisiologia
10.
Development ; 125(4): 579-87, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9435279

RESUMO

In a differential screen for downstream genes of the neural inducers, we identified two extremely early neural genes induced by Chordin and suppressed by BMP-4: Zic-related-1 (Zic-r1), a zinc finger factor related to the Drosophila pair-rule gene odd-paired, and Sox-2, a Sry-related HMG factor. Expression of the two genes is first detected widely in the prospective neuroectoderm at the beginning of gastrulation, following the onset of Chordin expression and preceding that of Neurogenin (Xngnr-1). Zic-r1 mRNA injection activates the proneural gene Xngnr-1, and initiates neural and neuronal differentiation in isolated animal caps and in vivo. In contrast, Sox-2 alone is not sufficient to cause neural differentiation, but can work synergistically with FGF signaling to initiate neural induction. Thus, Zic-r1 acts in the pathway bridging the neural inducer with the downstream proneural genes, while Sox-2 makes the ectoderm responsive to extracellular signals, demonstrating that the early phase of neural induction involves simultaneous activation of multiple functions.


Assuntos
Proteínas de Ligação a DNA/biossíntese , Glicoproteínas , Substâncias de Crescimento/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular , Sistema Nervoso/crescimento & desenvolvimento , Proteínas Nucleares/biossíntese , Proteínas/farmacologia , Xenopus/crescimento & desenvolvimento , Xenopus/genética , Dedos de Zinco/fisiologia , Animais , Sequência de Bases , Proteína Morfogenética Óssea 4 , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/fisiologia , Primers do DNA/genética , Proteínas de Ligação a DNA/genética , Fatores de Crescimento de Fibroblastos/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Proteínas HMGB , Hibridização In Situ , Microinjeções , Proteínas Nucleares/genética , Reação em Cadeia da Polimerase , RNA Mensageiro/administração & dosagem , RNA Mensageiro/genética , Fatores de Transcrição SOXB1 , Transdução de Sinais , Fatores de Transcrição , Proteínas de Xenopus , Dedos de Zinco/genética
11.
Pathol Int ; 47(8): 578-80, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9293541

RESUMO

An 85-year-old man was found to have a calcified mass protruding from the joint space of the right temporomandibular joint (TMJ). Microscopically, the removed mass consisted of chondromyxoid tissue with atypical chondrocytes, resembling a cartilaginous tumor. However, the chondromyxoid tissue contained abundant deposits of rod-shaped to rhomboid crystals which proved to be calcium pyrophosphate dihydrate (CPPD) crystals. The review of the literature revealed that tophaceous pseudogout was the most common variant of CPPD deposition disease involving the TMJ.


Assuntos
Condrocalcinose/patologia , Articulação Temporomandibular/patologia , Idoso , Idoso de 80 Anos ou mais , Pirofosfato de Cálcio/metabolismo , Humanos , Masculino
13.
Acta Pathol Jpn ; 43(1-2): 82-5, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8465661

RESUMO

We describe a case of well differentiated adenocarcinoma of the gall-bladder that arose from a localized type of adenomyomatosis. Grossly, the cancer was located in the fundus and exhibited a polypoid and well demarcated nodule with multiple small cysts. Histologically, the nodule consisted of glandular structures and stroma containing bundles of smooth muscle cells. The glandular epithelia were varied in appearance, ranging from malignant to benign glands. The adenocarcinoma was limited to the nodule, with normal surface mucosal epithelia and without obvious stromal invasion.


Assuntos
Adenocarcinoma/patologia , Neoplasias da Vesícula Biliar/patologia , Vesícula Biliar/patologia , Adenocarcinoma/etiologia , Idoso , Neoplasias da Vesícula Biliar/complicações , Humanos , Hiperplasia , Masculino
14.
Acta Pathol Jpn ; 41(11): 824-8, 1991 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1664636

RESUMO

A rare case of malignant T-cell lymphoma with manifold histologic appearances was described. The lymphoma occurred in the stomach of a 50-year-old Japanese male. Grossly, the lymphoma exhibited a deeply ulcerated mass. Histologically, in addition to diffuse infiltrate of large lymphoid cells with deeply indented nuclei, there were many epithelioid cell granulomas, remarkable tissue eosinophilia and stromal fibrosis, mimicking inflammatory disease. Immunohistochemical studies and a gene analysis demonstrated the T-cell phenotype.


Assuntos
Linfoma de Células T/patologia , Neoplasias Gástricas/patologia , Biomarcadores Tumorais/análise , Southern Blotting , Núcleo Celular/ultraestrutura , DNA de Neoplasias/genética , Eosinofilia/patologia , Fibrose/patologia , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T/genética , Humanos , Imuno-Histoquímica , Linfoma de Células T/química , Linfoma de Células T/genética , Masculino , Pessoa de Meia-Idade , Muramidase/análise , Fenótipo , Proteínas S100/análise , Estômago/patologia , Estômago/ultraestrutura , Neoplasias Gástricas/química , Neoplasias Gástricas/genética
15.
Acta Pathol Jpn ; 41(8): 623-8, 1991 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1750359

RESUMO

We present two similar cases of rectal B-cell lymphoma with diagnostic problems. Grossly, both tumors appeared as a well demarcated polypoid mass with eroded mucosa. In spite of their histologic resemblance to reactive lymphoid hyperplasia, including the presence of lymph follicles, fibrosis and polyclonal plasma cells, both cases were diagnosed as malignant lymphoma of low-grade malignancy because of the full-thickness involvement of the rectum with diffusely infiltrated small or medium-sized lymphoid cells showing rare mitoses. In one case, clonal proliferation of differentiated B cells was demonstrated by analysis of gene rearrangement. Therapeutic problems related to low-grade malignant lymphoma in the rectum are also discussed.


Assuntos
Rearranjo Gênico do Linfócito B/genética , Linfoma de Células B/diagnóstico , Linfoma de Células B/genética , Neoplasias Retais/diagnóstico , Neoplasias Retais/genética , Adulto , Idoso , Linfócitos B/patologia , Southern Blotting , DNA de Neoplasias/genética , Diagnóstico Diferencial , Feminino , Humanos , Linfoma de Células B/patologia , Masculino , Neoplasias Retais/patologia
16.
Acta Pathol Jpn ; 40(9): 683-6, 1990 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2260475

RESUMO

We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma.


Assuntos
Medula Suprarrenal/patologia , Neoplasias das Glândulas Suprarrenais/etiologia , Neoplasias das Glândulas Suprarrenais/patologia , Medula Suprarrenal/metabolismo , Catecolaminas/sangue , Feminino , Humanos , Hiperplasia/complicações , Hiperplasia/metabolismo , Hiperplasia/patologia , Pessoa de Meia-Idade , Feocromocitoma/etiologia , Feocromocitoma/patologia , Fosfopiruvato Hidratase/metabolismo
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