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1.
Eur J Orthop Surg Traumatol ; 29(5): 1119-1124, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30864017

RESUMO

BACKGROUND: Tibial fractures have an incidence of 15% of all adult fractures. They have been shown to have the highest incidence of non-union in long bone fractures and the highest incidence of vascular injury. Evidence from the literature suggests that a good vascular supply is important to ensure bone union. The aim of our study was to prospectively assess the incidence of vascular injuries in open tibial fractures and determine whether they were associated with an increased risk of non-union. METHODS: We performed a prospective study to investigate the incidence of arterial injuries with computed tomography angiography (CTA) in patients with Gustilo-Anderson grade I-III open tibial fractures between 2013 and 2015. CTA was performed with the trauma series at acute admission and reported by two independent musculoskeletal radiologists. Patients were followed up with clinical and radiographic assessment for 1 year. RESULTS: We recruited 77 patients into the study, and 56 patients (47 males, 9 females) were available for the final analysis, between 16 and 90 years of age. At the initial assessment, 29% had signs of arterial injury with active extravasation in 5%. The most common site of injury was in the diaphysis (87.5%), and the commonest mechanism was a road traffic accident. We found no significant relation between occult vascular injury and non-union (p > 0.05). CONCLUSION: The incidence of vascular injury in open tibial fractures is 29%, and CTA is therefore a useful test in identifying vascular injuries that may require vascular intervention.


Assuntos
Fixação Interna de Fraturas , Fraturas Expostas , Fraturas não Consolidadas , Complicações Pós-Operatórias , Fraturas da Tíbia , Lesões do Sistema Vascular , Angiografia por Tomografia Computadorizada/métodos , Feminino , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Fraturas Expostas/complicações , Fraturas Expostas/epidemiologia , Fraturas Expostas/cirurgia , Fraturas não Consolidadas/etiologia , Fraturas não Consolidadas/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Fraturas da Tíbia/complicações , Fraturas da Tíbia/epidemiologia , Fraturas da Tíbia/cirurgia , Reino Unido/epidemiologia , Procedimentos Cirúrgicos Vasculares/métodos , Lesões do Sistema Vascular/diagnóstico , Lesões do Sistema Vascular/epidemiologia , Lesões do Sistema Vascular/etiologia
2.
J Microsc ; 269(3): 230-246, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28876453

RESUMO

Properties of a composite material made of a continuous matrix and particles often depend on microscopic details, such as contacts between particles. Focusing on processing raw focused-ion beam scanning electron microscope (FIB-SEM) tomography data, we reconstructed three mixed-matrix membrane samples made of 6FDA-ODA polyimide and silicalite-1 particles. In the first step of image processing, backscattered electron (BSE) and secondary electron (SE) signals were mixed in a ratio that was expected to obtain a segmented 3D image with a realistic volume fraction of silicalite-1. Second, after spatial alignment of the stacked FIB-SEM data, the 3D image was smoothed using adaptive median and anisotropic nonlinear diffusion filters. Third, the image was segmented using the power watershed method coupled with a seeding algorithm based on geodesic reconstruction from the markers. If the resulting volume fraction did not match the target value quantified by chemical analysis of the sample, the BSE and SE signals were mixed in another ratio and the procedure was repeated until the target volume fraction was achieved. Otherwise, the segmented 3D image (replica) was accepted and its microstructure was thoroughly characterized with special attention paid to connectivity of the silicalite phase. In terms of the phase connectivity, Monte Carlo simulations based on the pure-phase permeability values enabled us to calculate the effective permeability tensor, the main diagonal elements of which were compared with the experimental permeability. In line with the hypothesis proposed in our recent paper (Capek, P. et al. (2014) Comput. Mater. Sci. 89, 142-156), the results confirmed that the existence of particle clusters was a key microstructural feature determining effective permeability.

3.
Nat Genet ; 22(1): 63-8, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10319863

RESUMO

Mucosa-associated lymphoid tissue (MALT) lymphomas most frequently involve the gastrointestinal tract and are the most common subset of extranodal non-Hodgkin lymphoma (NHL). Here we describe overexpression of BCL10, a novel apoptotic signalling gene that encodes an amino-terminal caspase recruitment domain (CARD), in MALT lymphomas due to the recurrent t(1;14)(p22;q32). BCL10 cDNAs from t(1;14)-positive MALT tumours contained a variety of mutations, most resulting in truncations either in or carboxy terminal to the CARD. Wild-type BCL10 activated NF-kappaB but induced apoptosis of MCF7 and 293 cells. CARD-truncation mutants were unable to induce cell death or activate NF-kappaB, whereas mutants with C-terminal truncations retained NF-kappaB activation but did not induce apoptosis. Mutant BCL10 overexpression might have a twofold lymphomagenic effect: loss of BCL10 pro-apoptosis may confer a survival advantage to MALT B-cells, and constitutive NF-kappaB activation may provide both anti-apoptotic and proliferative signals mediated via its transcriptional targets.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Caspases/metabolismo , Linfoma de Zona Marginal Tipo Células B/genética , Proteínas de Neoplasias/genética , Sequência de Aminoácidos , Proteína 10 de Linfoma CCL de Células B , Sítios de Ligação , Northern Blotting , Morte Celular/genética , Linhagem Celular , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 14/genética , DNA/química , DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Masculino , Dados de Sequência Molecular , Mutação , NF-kappa B/metabolismo , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Estrutura Terciária de Proteína , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Distribuição Tecidual , Translocação Genética , Células Tumorais Cultivadas
4.
Rozhl Chir ; 92(12): 694-8, 2013 Dec.
Artigo em Tcheco | MEDLINE | ID: mdl-24479513

RESUMO

INTRODUCTION: Repeated pulmonary resections are predominantly used in sarcomas, colorectal cancer, Grawitz tumours, and at a young age in general. Patients with the recurrence of pulmonary metastases within a period of six months have a poor prognosis. MATERIAL AND METHODS: During the period from I/1997 to XII/2011, a total of 165 operations were performed in 149 patients. 11patients had multiple pulmonary resections. According to histological origin, sarcomas were found in 6 cases, Grawitz tumours in 2 cases, Schwannoma malignum in 1 case and laryngeal carcinoma in 1 case. There was synovialosarcoma, osteosarcoma, rhabdomyosarcoma, alveolar sarcoma and uterine sarcoma in the group of sarcomas. RESULTS: In our retrospective study, the most commonly used approach was muscle-sparing vertical thoracotomy in 14 patients, posterolateral thoracotomy in 8 patients, VATS in 3 patients and clamshell thoracotomy in 3 patients. We performed 22 extraanatomic resections - of which 3 times VATS, 6 times lobectomy (of which 1 completion pneumonectomy). We observed complications in 6 cases (small air leak in 3 patients, wound infection in 3 patients) in the postoperative period. No rethoracotomy for complications was needed, lethality was 0. The overall 5-year survival that we observed was 45.4%. CONCLUSION: Surgery is an integral part of complex oncological care. What is extremely important is strict selection of patients eligible for surgery for repeated resections and, of course, an experienced team of thoracic surgeons, but also other physicians. When performed by experienced specialists, surgical treatment of lung metastases is a safe and very useful procedure.


Assuntos
Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/cirurgia , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Pneumonectomia , Prognóstico , Reoperação , Estudos Retrospectivos , Taxa de Sobrevida
5.
Rozhl Chir ; 91(12): 654-9, 2012 Dec.
Artigo em Tcheco | MEDLINE | ID: mdl-23448703

RESUMO

The wound is a damage of tissue. The process of healing is influenced by many systemic and local factors. The most crucial and the most discussed local factor of wound healing is infection. Surgical site infection in the wound is caused by micro-organisms. This information is known for many years, however the conditions leading to an infection occurrence have not been sufficiently described yet. Correct sampling technique, correct storage, transportation, evaluation, and valid interpretation of these data are very important in clinical practice. There are many methods for microbiological sampling, but the best one has not been yet identified and validated. We aim to discuss the problem with the focus on the imprint technique.


Assuntos
Manejo de Espécimes/métodos , Infecção da Ferida Cirúrgica/microbiologia , Humanos
6.
Klin Onkol ; 35(2): 128-131, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35459337

RESUMO

BACKGROUND: Squamous cell carcinoma of the head and neck is characterized by local invasiveness and metastases to regional lymph nodes. In 60% of cases, these tumours are dia-gnosed at an advanced stage, and the prognosis is unfavorable. One of the important factors of local, hematogenous or lymphogenic spread of the tumour in the human body is tumour cells migration ability. Advanced microscopic methods provide a new perspective on cell migration. PURPOSE: This paper presents a coherence controlled holographic microscopy method that provides a non-invasive quantitative evaluation of morphological and dynamic properties of living tumour cells. In connection with this method, new potential bio-markers are emerging, the significance of which, however, needs to be verified by correlation with clinical data.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Biomarcadores , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Microscopia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço
7.
Parasite Immunol ; 33(11): 621-31, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21992445

RESUMO

Helminth parasite infections are associated with predominant Th2-type cytokine responses, and parasite glycoconjugates have been recognized as partially responsible for such immune bias. It has been proved that Echinococcus granulosus evokes a Th2-type cytokine pattern characterized by a high production of IL-4, IL-5, IL-6 and IL-10, and no or mild IFN-γ levels in animal models and in patients with cystic echinococcosis, respectively. Here, we show that E4(+) (a glycoconjugate-enriched fraction from E. granulosus protoscolex) stimulated the secretion of a high concentration of IL-6, followed by IL-10 and TNF-α by normal peritoneal B cells. We determined that E4(+) bound to the surface of peritoneal B cells and induced their activation and, also, triggered the differentiation of peritoneal B cells into IgM-, IgG2b- and IgG3-secreting cells in a T-independent way. Interestingly, the IgM released by E4(+) -stimulated peritoneal B cells from normal mice recognized protoscolex antigens. Results showed that, after the encounter with antigens from E. granulosus protoscolex, peritoneal B cells are a source of Th2-type cytokines and polyclonal antibodies, some of which recognize parasite antigens, suggesting that peritoneal B cells can condition the outcome of the infection.


Assuntos
Anticorpos Anti-Helmínticos/biossíntese , Linfócitos B/imunologia , Equinococose/imunologia , Echinococcus granulosus/imunologia , Glicoconjugados/imunologia , Animais , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia , Linfócitos B/metabolismo , Diferenciação Celular , Células Cultivadas , Equinococose/parasitologia , Echinococcus granulosus/metabolismo , Feminino , Interações Hospedeiro-Parasita , Interleucina-10/biossíntese , Interleucina-10/imunologia , Interleucina-6/biossíntese , Interleucina-6/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Peritônio/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologia
8.
Eur J Vasc Endovasc Surg ; 41(3): 391-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21163675

RESUMO

OBJECTIVES: Wounds of the lower limb in patients with diabetes are frequently difficult to heal. Some wounds fail to heal despite optimal medical and surgical care. This review examines the evidence for whether free tissue transfer techniques may reduce the requirement of amputation in these patients. DESIGN: A systematic review. MATERIALS & METHODS: Pubmed, Embase, AMED, SCOPUS and CINAHL and Cochrane Library were searched for all articles on free tissue transfer in lower limb wounds in patients with diabetes (September 2010). Current experience, indications and outcomes were analysed. RESULTS: 528 patients from 18 studies were included in the systematic review. 66% of patients had concomitant revascularisation with bypass surgery. 63% of flaps were muscle based, 35% fasciocutaneous and 1.7% omental. Pooled in-hospital mortality rate was 4.4%, flap survival was 92% and limb salvage rate of 83.4% over a 28 months average follow-up time. CONCLUSIONS: In conclusion free tissue transfer achieves successful wound healing in selected patients with diabetes and difficult to heal wounds that would have required amputation. Pre-operative optimisation of vascular supply and eradication of infection is key to success. Objective wound assessment scores and a clear multidisciplinary team (MDT) approach would improve patient care.


Assuntos
Pé Diabético/cirurgia , Extremidade Inferior/irrigação sanguínea , Retalhos Cirúrgicos , Cicatrização , Adolescente , Adulto , Amputação Cirúrgica , Pé Diabético/mortalidade , Pé Diabético/patologia , Feminino , Mortalidade Hospitalar , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Reoperação , Retalhos Cirúrgicos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares , Adulto Jovem
9.
Rozhl Chir ; 90(11): 631-3, 2011 Nov.
Artigo em Tcheco | MEDLINE | ID: mdl-22442873

RESUMO

The authors discuss about questions of possibility pneumonectomy in concept of lung metastasis therapy. They analysed in detail indications, surgery, complications, survival and factors of survival. The authors also introduce case report of one patient with pneumonectomy in your group of patients.


Assuntos
Carcinoma de Células Renais/secundário , Neoplasias Pulmonares/secundário , Pneumonectomia , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade
10.
Rozhl Chir ; 90(11): 634-6, 2011 Nov.
Artigo em Tcheco | MEDLINE | ID: mdl-22442874

RESUMO

The authors present in the following case review a patient with spontaneous pneumomediastinum which can be on of the causes of acute chest pain and it is necessary to think about it in the differential diagnosis of this condition.


Assuntos
Enfisema Mediastínico/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Enfisema Mediastínico/terapia , Pessoa de Meia-Idade
11.
J Mol Biol ; 433(1): 166687, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33098857

RESUMO

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive joint destruction associated with increased pro-inflammatory mediators. In inflammatory microenvironments, exogenous ATP (eATP) is hydrolyzed to adenosine, which exerts immunosuppressive effects, by the consecutive action of the ectonucleotidases CD39 and CD73. Mature B cells constitutively express both ectonucleotidases, converting these cells to potential suppressors. Here, we assessed CD39 and CD73 expression on B cells from treated or untreated patients with RA. Neither the frequency of CD73+CD39+ and CD73-CD39+ B cell subsets nor the levels of CD73 and CD39 expression on B cells from untreated or treated RA patients showed significant changes in comparison to healthy controls (HC). CpG+IL-2-stimulated B cells from HC or untreated RA patients increased their CD39 expression, and suppressed CD4+ and CD8+ T cell proliferation and intracellular TNF-production. A CD39 inhibitor significantly restored proliferation and TNF-producing capacity in CD4+ T cells, but not in CD8+ T cells, from HC and untreated RA patients, indicating that B cells from untreated RA patients conserved CD39-mediated regulatory function. Good responder patients to therapy (R-RA) exhibited an increased CD39 but not CD73 expression on B cells after treatment, while most of the non-responder (NR) patients showed a reduction in ectoenzyme expression. The positive changes of CD39 expression on B cells exhibited a negative correlation with disease activity and rheumatoid factor levels. Our results suggest modulating the ectoenzymes/ADO pathway as a potential therapy target for improving the course of RA.


Assuntos
Apirase/metabolismo , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Imunomodulação , Adenosina/metabolismo , Apirase/genética , Artrite Reumatoide/patologia , Artrite Reumatoide/terapia , Linfócitos B Reguladores/imunologia , Linfócitos B Reguladores/metabolismo , Estudos de Casos e Controles , Citocinas/biossíntese , Gerenciamento Clínico , Suscetibilidade a Doenças , Expressão Gênica , Humanos , Ativação Linfocitária , Contagem de Linfócitos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do Tratamento
12.
Rozhl Chir ; 88(5): 222-4, 2009 May.
Artigo em Tcheco | MEDLINE | ID: mdl-19642337

RESUMO

In this case report the authors present a case of mediastinal malignant teratoma of a 23 years old patient, who suddenly suffers form chest pain as the only symptom. During examination is a huge mediastinal tumor diagnosed. After histological diagnosis is a radical surgery performed. According to the definitive histology is an adjutant oncological treatment indicated. The aim of our report is to think always about the mediastinal tumors as one of the possible cause of thoracic pain.


Assuntos
Neoplasias do Mediastino , Teratoma , Adulto , Dor no Peito/etiologia , Humanos , Masculino , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/cirurgia , Teratoma/diagnóstico , Teratoma/patologia , Teratoma/cirurgia , Adulto Jovem
13.
Rozhl Chir ; 88(5): 229-34, 2009 May.
Artigo em Tcheco | MEDLINE | ID: mdl-19642339

RESUMO

UNLABELLED: The aim of the retrospective clinical study was the analysis of the 20 high-risk patients operated in our department within years 2000-2008 by the modified Eloesser procedure for the serious thoracic empyema. MATERIAL AND METHODS: We have analyzed the data of the 17 men and 3 women. The most important objectives were the cause of the disease, type of procedure, perioperative mortality, length of stay and subsequent procedures. The underlying disease was the malignant intrathoracic disease in 40%, diabetes mellitus was found in 25%. The cause of empyema was pleuropneumonia in 45%, postresectional empyema occurred in 35%. RESULTS: There were two perioperative deaths (10%), remaining patients were all dismissed in a stabilized condition the 22nd postoperative day at average. Six subsequent reconstructive procedures were performed. There was no early death for the postpneumonectomy empyema. CONCLUSION: In case of the serious pleural empyema in a high-risk patient is the modified Eloesser procedure safe and life saving surgical operation. The timing of the procedure and correct indication for surgery are essential.


Assuntos
Empiema Pleural/cirurgia , Pleura/cirurgia , Toracostomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Empiema Pleural/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Torácicos
15.
Leukemia ; 10(1): 159-66, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8558922

RESUMO

The phenotypic and biologic properties of malignant cells in a case of aggressive mastocytosis with multi-organ involvement, circulating mast cell precursors and absence of skin infiltrates were analyzed. Circulating mast cell precursors were detected by immunostaining using antibodies against mast cell tryptase as well as by electron microscopy. These progenitors were tryptase+/chymase- (MCT) and accounted for 10 to 20% of nucleated mononuclear blood cells (MNC). A subset of them contained metachromatic granules. As assessed by combined toluidine blue/immunofluorescence staining, the granulated mast cell precursors were found to express CD9 (P24), CD33 (gp67) and CD44 (Pgp-1), but not basophil-related markers (CD11b (C3biR), CDw17 (lactosylceramide), CD123 (il-3R alpha))or monocyte-related antigens (CD14, CD15). Expression of the mast cell growth factor (MGF) receptor, c-kit(CD117), was also demonstrable, whereas the skin mast cell marker C5aR (CD88) could not be detected on mast cell precursors. The ligand of c-kit, recombinant human (rh) stem cell factor (SCF = MGF), induced histamine release from circulating mast cell progenitors, whereas rhC5a, a potent skin mast cell-/basophil-agonist, was ineffective over the dose-range (10(-9) to 10(-7(M)) tested. Analysis of mast cell antigens in malignant mastocytosis or mast cell leukemias may be helpful to establish a diagnosis and to determine the phenotype of the clone.


Assuntos
Células-Tronco Hematopoéticas/patologia , Mastócitos/patologia , Sarcoma de Mastócitos/patologia , Células-Tronco Neoplásicas/patologia , Adulto , Quimases , Grânulos Citoplasmáticos/patologia , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/metabolismo , Liberação de Histamina , Humanos , Imuno-Histoquímica , Imunofenotipagem , Masculino , Mastócitos/imunologia , Mastócitos/metabolismo , Sarcoma de Mastócitos/sangue , Sarcoma de Mastócitos/imunologia , Microscopia Eletrônica , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Serina Endopeptidases/metabolismo , Fator de Células-Tronco/metabolismo , Fator de Células-Tronco/farmacologia , Triptases
16.
Environ Sci Pollut Res Int ; 22(7): 4949-63, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25345925

RESUMO

Polybrominated diphenyl ethers (PBDE) were, and in some countries still are, used as flame retardants for plastic materials. When released from plastics, PDBE cause harm to the environment. This creates the incentive for further investigation of the PBDE degradation. This work focused on a formulation of a PBDE photodegradation model based on the PBDE properties obtained by the quantum chemical calculations. The proposed model predicted degradation routes of arbitrary PBDE congener. The routes of selected congeners were validated by the two independently published data sets and showed the high fitting degree. The model can be easily modified for any reactor system if the initial reaction rate constant of one congener is available for the given system.


Assuntos
Retardadores de Chama/análise , Éteres Difenil Halogenados/química , Modelos Teóricos , Fotólise , Simulação por Computador , Estrutura Molecular , Reprodutibilidade dos Testes
17.
FEBS Lett ; 458(2): 257-60, 1999 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-10481076

RESUMO

The expression of the inducible haem oxygenase (HO-1) gene was examined in different skeletal muscles. Rats were treated with haemin and a time course of HO-1 mRNA expression was determined in soleus and extensor digitorum longus (EDL) muscles. Fibre type composition and tissue myoglobin content were also measured. We found that HO-1 mRNA expression markedly increased in soleus (type I fibres) muscle but was only slightly affected in EDL (type II fibres). HO-1 expression directly correlated with both percentage of red fibres and tissue myoglobin. These data demonstrate that HO-1 gene expression follows a fibre type-specific pattern which might indicate an important role for this protein in the maintenance of skeletal muscle function.


Assuntos
Heme Oxigenase (Desciclizante)/biossíntese , Fibras Musculares Esqueléticas/enzimologia , Músculo Esquelético/enzimologia , Adenosina Trifosfatases/metabolismo , Animais , Di-Hidrolipoamida Desidrogenase/metabolismo , Indução Enzimática/genética , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase-1 , Hemina/administração & dosagem , Injeções Intraperitoneais , Masculino , Fibras Musculares de Contração Rápida/enzimologia , Fibras Musculares de Contração Lenta/enzimologia , Mioglobina/metabolismo , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley
18.
Am J Surg Pathol ; 14(5): 439-48, 1990 May.
Artigo em Inglês | MEDLINE | ID: mdl-2158242

RESUMO

We report the clinicopathologic findings of 41 patients with Ki-1 (CD30)-positive large cell lymphoma. The median age was 50 years; 13 patients were under 40 years of age. Ten patients presented with extranodal disease. Fifty-five percent of the patients presented with stage I or II disease, and bone marrow involvement was histologically documented in 30% and occurred exclusively in patients over 40 years of age. Two cytomorphologically distinct groups of Ki-1--positive large cell lymphomas could be separated. Group A lymphomas consisted of pleomorphic large cells, sometimes with wreathlike and embryo-like nuclei, whereas group B lymphomas displayed a rather monomorphic appearance. Clinically the two groups of lymphomas differed with respect to stage of disease, frequency of bone marrow involvement, and median survival. On paraffin sections, the Ki-1--related antibody Ber-H2 provided excellent staining results in all cases. Immunologic phenotyping disclosed a T cell type in the majority of cases, revealed marked loss of differentiation antigens, and frequent expression of HLA-DR and IL-2 receptor. The overall median survival was 13 months. Age below 40 years, limited stage of disease (I and II), and, although not statistically significant, lymphoma morphology were associated with longer survival. We conclude, that Ki-1--positive large cell lymphomas represent a morphologically and immunologically heterogeneous category of hematolymphoid neoplasms derived from dedifferentiated and activated lymphoid cells with marked age-dependent prognosis.


Assuntos
Antígenos de Diferenciação/análise , Antígenos de Neoplasias/análise , Linfoma Folicular/patologia , Adulto , Idoso , Anticorpos Monoclonais/análise , Anticorpos Monoclonais/imunologia , Antígenos de Diferenciação/imunologia , Antígenos de Neoplasias/imunologia , Medula Óssea/patologia , Feminino , Humanos , Antígeno Ki-1 , Linfonodos/patologia , Linfoma Folicular/imunologia , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Fenótipo , Taxa de Sobrevida
19.
Br J Pharmacol ; 125(7): 1437-44, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9884071

RESUMO

The contribution of haeme oxygenase-derived carbon monoxide (CO) to the regulation of vascular tone in thoracic aorta was investigated following induction of the inducible isoform of haeme oxygenase (HO-1). Isometric smooth muscle contractions were recorded in isolated rat aortic ring preparations. Rings were incubated in the presence of the nitric oxide (NO) donor S-nitroso-N-acetyl penicillamine (SNAP, 500 microM) for 1 h, then repetitively washed and maintained for a further 4 h prior to producing a concentration-response curve to phenylephrine (PE, 1-3000 nM). Treatment with SNAP resulted in increased mRNA and protein expression of aortic HO-1 and was associated with a significant suppression of the contractile response to PE (P<0.05 vs control). Immunohistochemical staining procedures revealed marked HO-1 expression in the endothelial layer and, to a lesser extent, in smooth muscle cells. Induction of HO-1 in SNAP-treated rings was associated with a higher 14CO release compared to control, as measured by scintillation counting after incubation of aortas with [2-14C]-L-glycine, the precursor of haeme. Guanosine 3',5'-monophosphate (cyclic GMP) content was also greatly enhanced in aortas expressing high levels of HO-1. Incubation of aortic rings with the NO synthase inhibitor, NG-monomethyl-L-arginine (100 microM), significantly (P<0.05) increased the contractile response to PE in controls but failed to restore PE-mediated contractility in SNAP-treated rings. In contrast, the selective inhibitor of haeme oxygenase, tin protoporphyrin IX (SnPP-IX, 10 microM), restored the pressor response to PE in SNAP-treated rings whilst markedly reducing CO and cyclic GMP production. We conclude that up-regulation of the HO-1/CO pathway significantly contributes to the suppression of aortic contractility to PE. This effect appears to be mediated by the elevation of cyclic GMP levels and can be reversed by inhibition of the haeme oxygenase pathway.


Assuntos
Monóxido de Carbono/fisiologia , Heme Oxigenase (Desciclizante)/biossíntese , Resistência Vascular/fisiologia , Animais , Aorta Torácica , Monóxido de Carbono/metabolismo , GMP Cíclico/metabolismo , Interações Medicamentosas , Indução Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Expressão Gênica/efeitos dos fármacos , Heme Oxigenase (Desciclizante)/antagonistas & inibidores , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase-1 , Masculino , Tono Muscular , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Penicilamina/análogos & derivados , Penicilamina/farmacologia , Fenilefrina/farmacologia , Ratos , Ratos Endogâmicos Lew , Resistência Vascular/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos
20.
Am J Med Genet ; 65(1): 27-35, 1996 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-8914737

RESUMO

Autosomal-dominant long QT syndrome (LQT) is an inherited disorder, predisposing affected individuals to sudden death from tachyarrhythmias. To identify the gene(s) responsible for LQT, we identified and characterized an LQT family consisting of 48 individuals. DNA was screened with 150 microsatellite polymorphic markers encompassing approximately 70% of the genome. We found evidence for linkage of the LQT phenotype to chromosome 7(q35-36). Marker D7S636 yielded a maximum lod score of 6.93 at a recombination fraction (theta) of 0.00. Haplotype analysis further localized the LQT gene within a 6.2-cM interval. HERG encodes a potassium channel which has been mapped to this region. Single-strand conformational polymorphism analyses demonstrated aberrant bands that were unique to all affected individuals. DNA sequencing of the aberrant bands demonstrated a G to A substitution in all affected patients; this point mutation results in the substitution of a highly conserved valine residue with a methionine (V822M) in the cyclic nucleotide-binding domain of this potassium channel. The cosegregation of this distinct mutation with LQT demonstrates that HERG is the LQT gene in this pedigree. Furthermore, the location and character of this mutation suggests that the cyclic nucleotide-binding domain of the potassium channel encoded by HERG plays an important role in normal cardiac repolarization and may decrease susceptibility to ventricular tachyarrhythmias.


Assuntos
Proteínas de Transporte de Cátions , Proteínas de Ligação a DNA , Síndrome do QT Longo/genética , Mutação , Nucleotídeos Cíclicos/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio/genética , Transativadores , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Sítios de Ligação/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 7 , Canal de Potássio ERG1 , Canais de Potássio Éter-A-Go-Go , Feminino , Ligação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Polimorfismo Conformacional de Fita Simples , Canais de Potássio/química , Conformação Proteica , Regulador Transcricional ERG
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