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1.
Orthopade ; 46(8): 656-664, 2017 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-28755164

RESUMO

A combination of allogeneic and autologous bone transplants is frequently used for the biological reconstruction of bone defects. Autologous bone transplants can be used either in the form of structural or cancellous bone transplants. The osteogenic potential of autologous cancellous bone is well-known and is still the gold standard with respect to osteoinduction and remodelling. Structural transplants, such as fibular and tricortical iliac crest grafts can be transplanted either free, i.e. non-vascularized or vascularized with anastomosed vessels. Allogeneic bone transplants can be used in a spongiose or structural form. In revision endoprosthetics the use of allogeneic bone transplants has essentially been reduced to impaction grafting, due to the introduction of trabecular metal as a permanently stable substitute. Allogeneic transplants have been restricted due to 3D-printing and the associated individually adapted reconstruction. In individual cases combined reconstruction consisting of allograft and endoprosthesis provide the advantage of safe load transmission and permanent reconstruction by the endoprosthesis and the possibility of soft tissue insertion of the allograft.


Assuntos
Transplante Ósseo/métodos , Aloenxertos/irrigação sanguínea , Autoenxertos/irrigação sanguínea , Substitutos Ósseos , Terapia Combinada , Humanos , Microcirurgia , Impressão Tridimensional , Desenho de Prótese , Procedimentos de Cirurgia Plástica , Reoperação
2.
Appl Neuropsychol ; 18(1): 54-60, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21390901

RESUMO

This study offers new evidence for the validity of the interpretation of the Rey Visual Design Learning Test (RVDLT) test score. The RVDLT is a design memory test that requires constructive output (drawings of memorized test items) in the recall phase. We mainly focused on response processes and tested the effect of a verbal and a motor memory strategy on test performance. Strategies were only explained and participants (12- to 15-year-olds) were stimulated to use them in a subsequent test session. In the verbal encoding condition, participants were instructed to name the test items of the RVDLT. In the copy condition, participants copied test items with an empty pen concurrent with test item presentation (rehearsal of motor sequences). Test performances were compared to a control group. No significant difference in RVDLT test score was detected between the verbal encoding group and the control group. However, the copy group scored significantly lower than the other two groups. Results are discussed in light of the validity of the test interpretation.


Assuntos
Memória , Testes Neuropsicológicos , Desempenho Psicomotor , Habilidades para Realização de Testes/psicologia , Aprendizagem Verbal , Adolescente , Criança , Feminino , Humanos , Masculino , Distribuição Aleatória
3.
J Cell Biol ; 128(5): 863-77, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7876310

RESUMO

KAR1 has been identified as an essential gene which is involved in karyogamy of mating yeast cells and in spindle pole body duplication of mitotic cells (Rose, M. D., and G. R. Fink. 1987. Cell. 48:1047-1060). We investigated the cell cycle-dependent localization of the Kar1 protein (Kar1p) and its interaction with other SPB components. Kar1p is associated with the spindle pole body during the entire cell cycle of yeast. Immunoelectron microscopic studies with anti-Kar1p antibodies or with the monoclonal antibody 12CA5 using an epitope-tagged, functional Kar1p revealed that Kar1p is associated with the half bridge or the bridge of the spindle pole body. Cdc31p, a Ca(2+)-binding protein, was previously identified as the first component of the half bridge of the spindle pole body (Spang, A., I. Courtney, U. Fackler, M. Matzner, and E. Schiebel. 1993. J. Cell Biol. 123:405-416). Using an in vitro assay we demonstrate that Cdc31p specifically interacts with a short sequence within the carboxyl terminal half of Kar1p. The potential Cdc31p-binding sequence of Kar1p contains three acidic amino acids which are not found in calmodulin-binding peptides, explaining the different substrate specificities of Cdc31p and calmodulin. Cdc31p was also able to bind to the carboxy terminus of Nuflp/Spc110p, another component of the SPB (Kilmartin, J. V., S. L. Dyos, D. Kershaw, and J. T. Finch. 1993. J. Cell Biol. 123:1175-1184). The association of Kar1p with the spindle pole body was independent of Cdc31p. Cdc31p, on the other hand, was not associated with SPBs of kar1 cells.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ciclo Celular , Ciclo Celular/fisiologia , Proteínas Fúngicas/metabolismo , Proteínas Nucleares/metabolismo , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/crescimento & desenvolvimento , Fuso Acromático/metabolismo , Sequência de Bases , Proteínas de Ligação a Calmodulina , Compartimento Celular , Proteínas do Citoesqueleto , Imunofluorescência , Proteínas Fúngicas/genética , Proteínas Fúngicas/imunologia , Modelos Biológicos , Dados de Sequência Molecular , Proteínas Nucleares/genética , Proteínas Nucleares/imunologia , Ligação Proteica , Proteínas Recombinantes de Fusão , Saccharomyces cerevisiae/ultraestrutura , Fuso Acromático/ultraestrutura
4.
J Cell Biol ; 123(2): 405-16, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8408222

RESUMO

Cdc31 mutants of Saccharomyces cerevisiae arrest at the nonpermissive temperature with large buds, G2 DNA content and, a single, abnormally large spindle pole body (SPB) (Byers, B. 1981. Molecular Genetics in Yeast. Alfred Benzon Symposium. 16:119-133). In this report, we show that the CDC31 gene product is essential for cell viability. We demonstrate that purified CDC31 protein binds Ca2+ and that this binding is highly specific. Taken together, three lines of evidence indicate that CDC31 is a component of the SPB. First, CDC31 cofractionates with enriched preparations of SPBs. Second, immunofluorescence staining indicates that CDC31 colocalizes with a known SPB component. Third, immunoelectron microscopy with whole cells and with isolated SPBs reveals that CDC31 is localized to the half bridge of the SPB, which lies immediately adjacent to the SPB plaques. CDC31 was detected mainly at the cytoplasmic side of the half bridge and, therefore, defines a further substructure of the SPB. We suggest that CDC31 is a member of a family of calcium-binding, centrosome-associated proteins from a phylogenetically diverse group of organisms.


Assuntos
Proteínas de Ligação ao Cálcio/análise , Proteínas de Ciclo Celular , Proteínas Fúngicas/análise , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/citologia , Fuso Acromático/química , Animais , Sequência de Bases , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/fisiologia , Divisão Celular/fisiologia , Sobrevivência Celular/fisiologia , DNA/análise , DNA/genética , Imunofluorescência , Proteínas Fúngicas/genética , Proteínas Fúngicas/fisiologia , Immunoblotting , Microscopia Imunoeletrônica , Dados de Sequência Molecular , Mutação/genética , Proteínas Nucleares/análise , Proteínas Nucleares/genética , Proteínas Nucleares/fisiologia , Saccharomyces cerevisiae/fisiologia , Fuso Acromático/fisiologia , Fuso Acromático/ultraestrutura
5.
J Cell Biol ; 142(3): 735-50, 1998 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-9700162

RESUMO

In a search for novel members of the alpha-actinin superfamily, a Dictyostelium discoideum genomic library in yeast artificial chromosomes (YAC) was screened under low stringency conditions using the acting-binding domain of the gelation factor as probe. A new locus was identified and 8.6 kb of genomic DNA were sequenced that encompassed the whole abpD gene. The DNA sequence predicts a protein, interaptin, with a calculated molecular mass of 204,300 D that is constituted by an actin-binding domain, a central coiled-coil rod domain and a membrane-associated domain. In Northern blot analyses a cAMP-stimulated transcript of 5.8 kb is expressed at the stage when cell differentiation occurs. Monoclonal antibodies raised against bacterially expressed interaptin polypeptides recognized a 200-kD developmentally and cAMP-regulated protein and a 160-kD constitutively expressed protein in Western blots. In multicellular structures, interaptin appears to be enriched in anterior-like cells which sort to the upper and lower cups during culmination. The protein is located at the nuclear envelope and ER. In mutants deficient in interaptin development is delayed, but the morphology of the mature fruiting bodies appears normal. When starved in suspension abpD- cells form EDTA-stable aggregates, which, in contrast to wild type, dissociate. Based on its domains and location, interaptin constitutes a potential link between intracellular membrane compartments and the actin cytoskeleton.


Assuntos
Dictyostelium/genética , Proteínas Fúngicas/genética , Proteínas dos Microfilamentos/genética , Actinina/química , Sequência de Aminoácidos , Animais , Adesão Celular , Compartimento Celular , Clonagem Molecular , AMP Cíclico/fisiologia , Dictyostelium/citologia , Proteínas Fúngicas/química , Proteínas Fúngicas/fisiologia , Regulação Fúngica da Expressão Gênica , Membranas Intracelulares/metabolismo , Proteínas dos Microfilamentos/química , Proteínas dos Microfilamentos/fisiologia , Dados de Sequência Molecular , Mutagênese , Homologia de Sequência de Aminoácidos , Frações Subcelulares
6.
J Natl Cancer Inst ; 84(23): 1798-802, 1992 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-1433369

RESUMO

BACKGROUND: Sulofenur is a diarylsulfonylurea with demonstrated antitumor activity in patients with advanced epithelial ovarian cancer refractory to standard chemotherapy. The dose-limiting toxic effects observed in phase I clinical trials have been anemia and methemoglobinemia, resulting in cyanosis. PURPOSE: The purposes of this study were to further define the response rate, toxic effects, and pharmacokinetics and pharmacodynamics of sulofenur in patients with advanced ovarian cancer. METHODS: We conducted a phase II trial of sulofenur at a dose of 800 mg/m2 per day in 35 patients with stage III or IV ovarian cancer refractory to standard chemotherapy. Pharmacokinetics and pharmacodynamics were analyzed by comparing sulofenur parent and metabolite plasma levels with methemoglobin levels. RESULTS: Partial responses lasting 6.5-18 weeks occurred in four (15%; 95% confidence interval = 4%-35%) of the 26 patients assessable for response. In addition, 42% (11) of the assessable patients had prolonged stable disease (median, 20 weeks). The first nine patients received sulofenur as a daily oral dose for 14 days, with a 21-day treatment cycle. However, they developed substantial anemia and methemoglobinemia. As a result, the next 26 patients received sulofenur daily for 5 days followed by 2 days of rest for 3 consecutive weeks, with a 28-day treatment cycle (5/2-day schedule). Preclinical models predicted that 2 days of rest would decrease toxicity while maintaining antitumor activity. Patients treated with the 5/2-day schedule had relatively less severe anemia and methemoglobinemia and needed fewer red blood cell transfusions (31% versus 78% of patients), but 31% still required dose reductions because of these toxic effects. The hydroxy and keto metabolites of sulofenur had prolonged plasma half-lives relative to the parent compound, and the difference was statistically significant. In addition, the correlations of metabolite concentrations with methemoglobin levels were higher than the correlation of sulofenur concentrations with methemoglobin levels, and those differences were statistically significant. CONCLUSION: We conclude that sulofenur has modest clinical activity in heavily pretreated patients with ovarian cancer. IMPLICATIONS: The toxic effects of anemia and methemoglobinemia may limit the ultimate clinical utility of diarylsulfonylureas until less toxic derivatives with alternate metabolic pathways can be identified.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Compostos de Sulfonilureia/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Carcinoma/patologia , Esquema de Medicação , Feminino , Humanos , Metemoglobinemia/induzido quimicamente , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Compostos de Sulfonilureia/efeitos adversos , Compostos de Sulfonilureia/farmacocinética
7.
J Clin Oncol ; 10(8): 1259-65, 1992 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1634915

RESUMO

PURPOSE AND METHODS: Diffuse small cleaved-cell lymphoma (DSCL) is a relatively uncommon non-hodgkin's lymphoma (NHL) in the United States and has not been the subject of recent in-depth study of factors predictive of outcome. It is unique among the NHL of intermediate grade because there is no evidence of a curable subset of patients. To investigate whether any laboratory data might predict outcome, we studied 33 cases collected during a 12-year period and correlated morphology, immunohistochemistry, and serum lactate dehydrogenase (LDH) with clinical data and outcome. RESULTS: We found that proliferative rate (Ki-67), cell lineage (T v B cell), and serum LDH were associated with significant differences in survival. A Ki-67 value greater than or equal to 20% was associated with a median survival of 20 months compared with 80 months for lower values (P = .0002); patients with tumors of T-cell lineage had a median survival of 20 months compared with 40 months for those with B-cell neoplasms (P = .0143); and a serum LDH greater than 225 IU/L was associated with a median survival of 8 months compared with 40 months for lower LDH levels (P = .0004). Blastoid morphology was also linked to a trend toward poor outcome (P = .08). Neither a history of low-grade lymphoma nor the presence of residual immunologically detectable follicles influenced outcome (P = .93 and .97, respectively). CONCLUSION: We conclude that high Ki-67, high LDH, and T-cell lineage each identify DSCL patients with poor outcome.


Assuntos
L-Lactato Desidrogenase/sangue , Subpopulações de Linfócitos , Linfoma não Hodgkin/mortalidade , Proteínas Nucleares/sangue , Adulto , Idoso , Linfócitos B , Divisão Celular , Feminino , Humanos , Imunofenotipagem , Antígeno Ki-67 , Linfoma não Hodgkin/enzimologia , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida , Linfócitos T
8.
Int J Radiat Oncol Biol Phys ; 25(5): 801-4, 1993 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-7683017

RESUMO

PURPOSE: This reviews the experience at the University of Arizona in an effort to define the minimum effective radiation dose for durable pain relief in the majority of patients with symptomatic multiple myeloma. METHODS AND MATERIALS: The records of 101 patients with multiple myeloma irradiated for palliation at the University of Arizona between 1975 and 1990 were reviewed. Three hundred sixteen sites were treated. Ten sites were asymptomatic, including six hemibody fields with advanced disease unresponsive to chemotherapy and four local fields with impending pathological fractures. Three hundred six evaluable symptomatic sites remained. The most common symptom was bone pain. Other symptoms included neurological impairment and a palpable mass. RESULTS: Total tumor dose ranged from 3.0 to 60 Gy, with a mean of 25 Gy. Symptom relief was obtained in 297 of 306 evaluable symptomatic sites (97%). Complete relief of symptoms was obtained in 26% and partial relief in 71%. Symptom relief was obtained in 92% of sites receiving a total dose less than 10 Gy (n = 13) and 98% of sites receiving 10 Gy or more (n = 293). No dose-response could be demonstrated. The likelihood of symptom relief was not influenced by the location of the lesion or the use of concurrent chemotherapy. Of the 297 responding sites, 6% (n = 19) relapsed after a median symptom-free interval of 16 months. Neither the probability of relapse nor the time to relapse was related to the radiation dose. Retreatment of relapsing sites provided effective palliation in all cases. CONCLUSION: Radiation therapy is effective in palliating local symptoms in multiple myeloma. A total dose of 10 Gy should provide durable symptom relief in the majority of patients.


Assuntos
Mieloma Múltiplo/radioterapia , Cuidados Paliativos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Dosagem Radioterapêutica , Estudos Retrospectivos
9.
Rofo ; 152(6): 677-81, 1990 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-2163073

RESUMO

MRI and scintigraphy were compared in 73 patients with 104 vertebral fractures aged between three days and 64 months. MRI was performed at 0.5 Tesla and 1.5 Tesla using T1- and T2-weighted spin-echo sequences. Isotope uptake was divided into four grades (normal, mild, moderate and marked increase). 92% of cases aged 0-6 months showed increased signal intensity on T2 sequences. This finding reflects edema in the bone. All these cases showed moderate or markedly increased uptake in 86%. The increased signal intensity in T2 spin-echo images provides a criterion for differentiating new from old fractures. The identification of normal fatty marrow in 91% of fractured vertebrae provides an important means for distinguishing traumatic from neoplastic fractures. One can also demonstrate bleeding, fatty change and sclerotic bone. MRI is less sensitive than scintigraphy, but more specific in following the posttraumatic healing process.


Assuntos
Fraturas Ósseas/diagnóstico , Vértebras Lombares/lesões , Imageamento por Ressonância Magnética , Compostos de Tecnécio , Vértebras Torácicas/lesões , Adolescente , Adulto , Difosfonatos , Estudos de Avaliação como Assunto , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Masculino , Pessoa de Meia-Idade , Cintilografia , Tecnécio , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/patologia , Fatores de Tempo
11.
EMBO J ; 18(12): 3305-16, 1999 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-10369671

RESUMO

The contractile vacuole expels water by forming a channel with the plasma membrane and thus enables cells to survive in a hypo-osmotic environment. Here we characterize drainin, a Dictyostelium protein involved in this process, as the first member of a protein family represented in fission yeast, Caenorhabditis elegans and man. Gene replacement in Dictyostelium shows that drainin acts at a checkpoint of channel formation between the contractile vacuole and the plasma membrane. A green fluorescent protein fusion of drainin localizes specifically to the contractile vacuole and rescues its periodic discharge in drainin-null cells. Drainin is a peripheral membrane protein, requiring a short hydrophobic stretch in its C-terminal region for localization and function. We suggest that drainin acts in a signaling cascade that couples a volume-sensing device in the vacuolar membrane to the membrane fusion machinery.


Assuntos
Dictyostelium/citologia , Fusão de Membrana , Proteínas de Membrana/metabolismo , Proteínas de Protozoários/metabolismo , Vacúolos/metabolismo , Sequência de Aminoácidos , Animais , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Sobrevivência Celular , Clonagem Molecular , Dictyostelium/crescimento & desenvolvimento , Dictyostelium/metabolismo , Endocitose , Endossomos/metabolismo , Deleção de Genes , Teste de Complementação Genética , Humanos , Membranas Intracelulares/metabolismo , Membranas Intracelulares/ultraestrutura , Proteínas de Membrana/química , Proteínas de Membrana/genética , Microscopia Eletrônica , Dados de Sequência Molecular , Pressão Osmótica , Fenótipo , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Homologia de Sequência de Aminoácidos , Vacúolos/genética , Vacúolos/ultraestrutura , Água/metabolismo
12.
Cancer ; 71(11): 3594-600, 1993 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-8490908

RESUMO

BACKGROUND: The clinical and prognostic significance of leukoerythroblastic anemia (LKEA) in patients with metastatic prostate cancer and, in general, patients with disseminated solid tumors is poorly understood. Therefore, the authors studied a population of patients with metastatic prostate cancer refractory to hormonal therapy to assess the incidence, clinical features, and prognostic implications of LKEA. METHODS: The medical records of 106 patients with hormone-refractory prostate cancer metastatic to bone seen at the Tucson Veterans Affairs Medical Center between 1985 and 1991 were reviewed retrospectively. The clinical and laboratory data, number of packed erythrocyte transfusions required, and length of survival from the time of diagnosis of hormone-refractory disease until last follow-up visit or death were investigated in 91 identified patients. RESULTS: Twenty-six of 91 patients (28.6%) were found to have LKEA. LKEA developed before or at the time of diagnosis of hormone-refractory disease in 8 patients and after diagnosis of hormone-refractory disease in 18 patients. The presence of LKEA was associated with significantly lower hemoglobin levels and platelet (Plt) counts and significantly higher total bilirubin, lactic dehydrogenase (LDH), and alkaline phosphatase values (P < 0.05). Leukopenia (< 4.0 x 10(9)/l leukocytes), thrombocytopenia (< 150 x 10(9)/l Plt), elevated LDH levels (> 220 U/l), and laboratory evidence of disseminated intravascular coagulation (DIC) were more common in patients with LKEA than in those without LKEA (P < 0.01). Microangiopathic hemolysis was seen in only 2 of 91 patients (2.1%). Patients with LKEA had significantly greater transfusion requirements compared with patients without LKEA (P < 0.0001), but the median survival length was not significantly different (9 months versus 11 months, respectively). The presence of DIC and LDH levels of 500 U/l or greater in patients with LKEA was associated with a poor prognosis. CONCLUSIONS: LKEA is a relatively common finding in patients with hormone-refractory metastatic prostate cancer and is associated with greater transfusion requirements. Its presence, however, does not affect survival significantly.


Assuntos
Anemia Mielopática/complicações , Neoplasias da Próstata/complicações , Idoso , Idoso de 80 Anos ou mais , Anemia Mielopática/sangue , Anemia Mielopática/mortalidade , Anemia Mielopática/terapia , Transfusão de Sangue , Coagulação Intravascular Disseminada/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Estudos Retrospectivos , Análise de Sobrevida
13.
EMBO J ; 15(12): 2935-43, 1996 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-8670794

RESUMO

Hisactophilins are myristoylated proteins that are rich in histidine residues and known to exist in Dictyostelium cells in a plasma membrane-bound and a soluble cytoplasmic state. Intracellular translocation of these proteins in response to pH changes was monitored using hisactophilin fusions with green fluorescent protein (GFP) and confocal laser scanning microscopy. Both the normal and a mutated non-myristoylated fusion protein shuffled within the cells in a pH-dependent manner. After lowering the pH, these proteins translocated within minutes between the cytoplasm, the plasma membrane and the nucleus. The role of histidine clusters on the surface of hisactophilin molecules in binding of the proteins to the plasma membrane and in their transfer to the nucleus is discussed on the basis of a pH switch mechanism.


Assuntos
Proteínas de Transporte/metabolismo , Núcleo Celular/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Luminescentes/metabolismo , Proteínas dos Microfilamentos , Proteínas de Protozoários , Actinas/metabolismo , Sequência de Aminoácidos , Animais , Transporte Biológico , Proteínas de Transporte/química , Membrana Celular/metabolismo , Dictyostelium/metabolismo , Proteínas Fúngicas/química , Proteínas de Fluorescência Verde , Concentração de Íons de Hidrogênio , Dados de Sequência Molecular , Ácido Mirístico , Ácidos Mirísticos/metabolismo , Ligação Proteica , Fatores de Tempo
14.
J Cell Sci ; 109 ( Pt 12): 2895-904, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9013337

RESUMO

The extracellular matrix protein fibulin-2 was shown to be a typical product of cultured human and mouse fibroblasts by several immunological assays. It is secreted and deposited in cells and tissues as a disulfide-bonded oligomer identical in size to the previously described recombinant fibulin-2. Most of the fibroblast fibulin-2 is deposited into a dense fibrillar meshwork which requires treatment with EDTA and/or 6 M urea for solubilization. Fibulin-2 and fibronectin are synthesized at equivalent levels and both colocalize in the fibrils as shown by immunofluorescence. Metabolic labelling and pulse-chase studies demonstrated fibulin-2 oligomers in detergent extracts of cells and their rapid translocation to extracellular EDTA-sensitive assembly forms. Unlike for fibronectin and fibulin-1 only a little fibulin-2 was found in the cell culture medium. Immunogold staining of confluent human fibroblasts showed localization of fibulin-2 to a fine meshwork or bundles of amorphous microfibrils in the matrix. This also demonstrated a distinct colocalization of fibulin-2 and fibronectin at the electron microscope level, indicating that the interaction between these two protein shown in in vitro assays may also exist in situ. No distinct colocalization of both proteins could, however, be observed with cross-striated fibrils of collagen I and collagen VI microfibrils.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Animais , Células Cultivadas , Ácido Edético/farmacologia , Fibroblastos/metabolismo , Humanos , Camundongos , Microscopia Eletrônica
15.
Blood ; 79(9): 2432-7, 1992 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-1373974

RESUMO

A distinct subset of patients with peripheral T-cell lymphoma (PTCL) is described which reacts with Leu-19 (CD56), an antibody that has been shown to identify the neural cell adhesion molecule (NCAM). These NCAM-positive PTCL patients (11 of a series of 46 PTCL; 24%) exhibited a striking predilection for unusual anatomic sites of involvement: central nervous system (36%), muscle (18%), gastrointestinal tract, and nasopharynx (27% each). Additional extranodal sites of involvement included the pituitary, thyroid, parathyroids, adrenals, and pancreas. The NCAM-positive subset also exhibited a characteristic phenotypic profile, with significantly lower expression of CD3 and CD5 compared with the NCAM-negative group. RNA transcripts consistent with the NCAM gene were detected in tissue samples from five Leu-19-positive cases using a reverse transcriptase-polymerase chain reaction assay, supporting the idea that Leu-19 recognizes NCAM in these patient samples. This suggests that the expression of the NCAM plays a role in the behavior and localization of lymphomas. Because of the unique clinical and phenotypic characteristics of this group it may be designated as "NCAM-positive peripheral T-cell lymphoma."


Assuntos
Moléculas de Adesão Celular Neuronais/análise , Linfoma de Células T Periférico/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Sequência de Bases , Moléculas de Adesão Celular Neuronais/genética , Feminino , Humanos , Linfoma de Células T Periférico/imunologia , Linfoma de Células T Periférico/patologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fenótipo , RNA/análise
16.
J Cell Sci ; 111 ( Pt 9): 1227-40, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9547299

RESUMO

To study centrosome motility and the interaction of microtubules with the cell cortex in mitotic, post-mitotic and interphase cells, (alpha)-tubulin was tagged in Dictyostelium discoideum with green fluorescent protein. Multinucleate cells formed by myosin II-null mutants proved to be especially suited for the analysis of the control of cleavage furrow formation by the microtubule system. After docking of the mitotic apparatus onto the cell cortex during anaphase, the cell surface is activated to form ruffles on top of the asters of microtubules that emanate from the centrosomes. Cleavage furrows are initiated at spaces between the asters independently of the positions of spindles. Once initiated, the furrows expand as deep folds without a continued connection to the microtubule system. Occurrence of unilateral furrows indicates that a closed contractile ring is dispensable for cytokinesis in Dictyostelium. The progression of cytokinesis in the multinucleate cells underlines the importance of proteins other than myosin II in specifying a cleavage furrow. The analysis of centrosome motility suggests a major role for a minus-end directed motor protein, probably cytoplasmic dynein, in applying traction forces on guiding microtubules that connect the centrosome with the cell cortex.


Assuntos
Anáfase , Centrossomo/fisiologia , Dictyostelium/citologia , Microtúbulos/fisiologia , Miosinas/deficiência , Animais , Membrana Celular/ultraestrutura , Núcleo Celular/ultraestrutura , Metabolismo Energético , Proteínas Fúngicas/fisiologia , Interfase , Microscopia Confocal , Microscopia Eletrônica , Microscopia de Fluorescência , Microscopia de Vídeo , Mitose , Movimento (Física) , Miosinas/fisiologia , Proteínas de Protozoários/fisiologia , Estresse Mecânico
17.
J Comput Assist Tomogr ; 20(4): 583-7, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8708060

RESUMO

PURPOSE: Our goal was to find a causal relation between disk degeneration in nonfused lumbar segments, back pain, and the angle of scoliotic curves 21-30 years after dorsal spondylodesis. METHOD: Thirty-two patients with scoliosis had been treated by dorsal spondylodesis 21-30 years prior to this study (mean 25.2 +/- 2.4 years). With use of MRI, signs of disk degeneration in the nonfused lumbar segments (n = 131, mean 4.1 +/- 1.4) were evaluated. Back pain evaluation was performed using the Oswestry disability score. On plain X-ray films, the angle of scoliotic curves was measured (Cobb technique). Percentage and absolute number of degenerated disks were compared to the fusion level (number of unfused caudal segments), the Oswestry score, and the Cobb angle. RESULTS: Disk degeneration was present in 20 of 32 patients (62.5%) and in 37 of 131 unfused lumbar segments (28.2%). Of eight patients (24.2%), seven had moderate back pain and one severe back pain. The mean lumbar scoliotic curve was 44.4 +/- 24.9 degrees. No statistically significant correlation was found between patients with disk degeneration and fusion level, amount of back pain, or lumbar scoliotic angle (p < 0.05). CONCLUSION: A lack of correlation between disk degeneration in unfused lumbar segments and other parameters like fusion level, back pain, and scoliotic angle can be assessed in the long-term follow-up of multisegment fusion of scoliotic curves.


Assuntos
Vértebras Lombares/patologia , Imageamento por Ressonância Magnética , Escoliose/diagnóstico , Fusão Vertebral , Adolescente , Dor nas Costas/etiologia , Criança , Feminino , Seguimentos , Humanos , Disco Intervertebral/patologia , Masculino , Estudos Prospectivos , Escoliose/patologia , Escoliose/cirurgia , Doenças da Coluna Vertebral/complicações , Doenças da Coluna Vertebral/diagnóstico
18.
Blood ; 81(2): 490-5, 1993 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-8093668

RESUMO

Multidrug-resistant (MDR) myeloma patients failing chemotherapy may express P-glycoprotein (PGP), which serves as an efflux pump protecting the neoplastic cells. Unknown is whether PGP expression might relate to prior cytotoxic drug exposure. To address this question, we studied 106 consecutive bone marrow samples from 104 myeloma patients with samples studied either before or after therapy and at the time of relapse. We performed an established immunocytochemical assay of PGP using an MDR-1-specific monoclonal antibody and correlated PGP status with prior chemotherapy dosage. Myeloma patients with no prior therapy had a low incidence of PGP expression (6%, 3/47), whereas those receiving chemotherapy had a significantly higher incidence (43%, 21/49) (P < .0001). A substantially higher incidence of PGP expression (50%, 83%, respectively) occurred when the total vincristine dose exceeded 20 mg and when doxorubicin exceeded 340 mg. In the 11 patients who received both high vincristine and doxorubicin dosages (> 20 mg, > 340 mg total dose) there was 100% incidence of PGP expression in the tumor cells. These data provided the basis for a predictive mathematical model from which dose-related PGP expression normograms were generated. Time with myeloma for PGP-negative patients (mean 33 months) had overlapping confidence limits with PGP-positive patients (mean 42 months), suggesting that disease duration was not a significant variable. PGP expression did not correlate with other clinical factors or immunophenotypic factors. Our findings indicate a strong correlation between PGP expression in myeloma and past chemotherapy in myeloma, in particular, related to prior exposure to the natural product agents vincristine and doxorubicin. Additionally, the proportion of PGP-positive plasma cells was significantly higher in the doxorubicin-treated patients than the nondoxorubicin-treated patients (87.7% v 65.17%; P = .013). Combined high vincristine and doxorubicin total dosage appear highly predictive of PGP expression.


Assuntos
Medula Óssea/metabolismo , Doxorrubicina/uso terapêutico , Glicoproteínas de Membrana/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Vincristina/uso terapêutico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Anticorpos Monoclonais , Antígenos CD/análise , Biópsia , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Relação Dose-Resposta a Droga , Resistência a Medicamentos , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Masculino , Glicoproteínas de Membrana/análise , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias , Análise de Regressão
19.
Acta Haematol ; 53(4): 206-18, 1975.
Artigo em Inglês | MEDLINE | ID: mdl-808930

RESUMO

The dilution in the circulating blood of lymphocytes lablled in vitro with 3H-cytidine was examined after autotransfusion in 9 patients with Hodgkin's disease (HD) stage II A-IV B, 5 of whom were untreated; in 2 untreated patients with carcinoma, and in 1 treated patient with scleroderma. The blood transit time of exchangeable lymphocytes was 37 +/- 18 min in the patients with HD and 26 +/- 6 min in the other patients. The proportion of exchangeable (recirculating) small blood lymphocytes was 39-84% in HD and 81-91% in the carcinoma patients. The relation between the size of the circulating pool of small blood lymphocytes and the total exchangeable (recirculating) lymphocyte pool was 1:20 to 1:30 in HD and 1:29 to 1:34 in the other patients. The absolute size of the recirculating pool of lymphocytes was 46-90 times 10(9) cells in HD and 100-150 times 10(9) cells in the carcinoma patients.


Assuntos
Transfusão de Sangue Autóloga , Doença de Hodgkin/terapia , Linfócitos , Adulto , Idoso , Citidina , Feminino , Doença de Hodgkin/sangue , Humanos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/terapia , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/terapia , Fatores de Tempo
20.
Nephrol Dial Transplant ; 11(1): 173-6, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8649629

RESUMO

BACKGROUND: As diabetes insipidus in brain-dead organ donors leads to hypovolaemia, hyponatraemia, and hypotension, desmopressin is recommended for treatment of diabetes insipidus. As its effect on early renal allograft function remains unclear, we conducted a study to evaluate the effect of desmopressin on renal-graft survival. METHODS: We report the results of a prospective study in 41 brain-dead organ donors (mean age 45 +/- 12 years) with diabetes insipidus, who were treated either with adequate fluid substitution and bolus application of desmopressin (desmopressin group; n = 22) or with volume substitution along (control group; n = 19). Donors as well as recipients of both groups were well matched with respect to age, sex, dopamine dosage, serum electrolytes, cold ischaemic time, HLA match, number of prior transplantations, and current cytotoxic antibodies. Early renal allograft function was evaluated in 71 recipients (mean age 48 +/- 4 years within 3 days after transplantation. RESULTS: Overall, primary non-function was observed in 26 (36.6%) of 71 recipients. The rate of primary non-function was significantly higher in the desmopressin group compared to the control group (desmopressin group 48.6%; control group 23.5%; P = 0.28). CONCLUSION: The use of desmopressin during organ procurement is associated with a higher rate of primary non-function of renal allografts.


Assuntos
Desamino Arginina Vasopressina/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Rim/fisiologia , Fármacos Renais/farmacologia , Obtenção de Tecidos e Órgãos , Adolescente , Adulto , Idoso , Morte Encefálica/fisiopatologia , Criança , Creatinina/metabolismo , Diabetes Insípido/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Homólogo
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