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1.
J. appl. oral sci ; 27: e20180348, 2019. tab, graf
Article in English | LILACS, BBO | ID: biblio-1019972

ABSTRACT

Abstract SOX2 is a transcription factor related to the maintenance of stem cells in a pluripotent state. Podoplanin is a type of transmembrane sialoglycoprotein, which plays an important role in tumor progression and metastasis. This study aims to determine association of SOX2 and podoplanin expression in the progression of oral squamous cell carcinomas and to elucidate the association between two proteins. Methodology: The immunohistochemical expression of SOX2 and podoplanin were evaluated in 60 cases of primary oral squamous cell carcinomas. The correlation between the SOX2 and podoplanin expression and the clinicopathological features of the tumors and the patient outcomes were assessed. Results: The expression of SOX2 was seen in 38/60 (63%) of the cases and the expression for podoplanin was seen in 45/60 (75%) cases. There was a significant inverse correlation between the expression of SOX2 and podoplanin with the tumor grade (p=0.002 and p=0.017, respectively). There was a high expression of SOX2 in 9/13 cases that presented with disease free survival. Survival analysis showed that a high expression of SOX2 correlated positively (p=0.043) with the disease-free survival. There was a significant positive association between the pattern of SOX2 and podoplanin expression (p=0.002). Conclusion: A high expression of SOX2 was associated with better disease-free survival. The expression of podoplanin was associated with the degree of differentiation of the tumors. Analysis of these biomarkers can aid in the prognosis and treatment of oral squamous cell carcinomas.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Mouth Neoplasms/pathology , Membrane Glycoproteins/analysis , Carcinoma, Squamous Cell/pathology , SOXB1 Transcription Factors/analysis , Reference Values , Time Factors , Immunohistochemistry , Biomarkers, Tumor/analysis , Statistics, Nonparametric , Disease Progression , Neoplasm Grading , Neoplasm Staging
2.
Braz. oral res. (Online) ; 33: e058, 2019. tab, graf
Article in English | LILACS | ID: biblio-1019608

ABSTRACT

Abstract Cementum is the mineralized tissue covering the tooth root that functions in tooth attachment and post-eruptive adjustment of tooth position. It has been reported to be highly similar to bone in several respects but remains poorly understood in terms of development and regeneration. Here, we investigate whether cementocytes, the residing cells in cellular cementum, have the potential to be protagonist in cementum homeostasis, responding to endocrine signals and directing local cementum metabolism. Cells from healthy erupted human teeth were isolated using sequential collagenase/EDTA digestions, and maintained in standard cell culture conditions. A cementocyte-like cell line was cloned (HCY-23, for human cementocyte clone 23), which presented a cementocyte compatible gene expression signature, including the expression of dentin matrix protein 1 ( DMP1 ), sclerostin ( SOST ), and E11/gp38/podoplanin ( E11 ). In contrast, these cells did not express the odontoblast/dentin marker dentin sialoprotein ( DSPP ). HCY-23 cells produced mineral-like nodules in vitro under differentiation conditions, and were highly responsive to inorganic phosphate (Pi). Within the limits of the present study, it can be concluded that cementocytes are phosphate-responsive cells, and have the potential do play a key role in periodontal homeostasis and regeneration.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Young Adult , Genetic Markers/genetics , Cell Culture Techniques/methods , Dental Cementum/cytology , Phosphates/pharmacology , Phosphoproteins/analysis , Phosphoproteins/genetics , Sialoglycoproteins/analysis , Sialoglycoproteins/genetics , Time Factors , Membrane Glycoproteins/analysis , Membrane Glycoproteins/genetics , Gene Expression , Cell Line , Analysis of Variance , Extracellular Matrix Proteins/analysis , Extracellular Matrix Proteins/genetics , Fluorescent Antibody Technique , Bone Morphogenetic Proteins/analysis , Bone Morphogenetic Proteins/genetics , Dental Cementum/metabolism , Adaptor Proteins, Signal Transducing , Molar/cytology
3.
Biol. Res ; 51: 21, 2018. graf
Article in English | LILACS | ID: biblio-950905

ABSTRACT

OBJECTIVE: To explore the precise mechanism of electroacupuncture (EA) to delay cognitive impairment in Alzheimer disease. Methods N -Acetylaspartate (NAA), glutamate (Glu) and myoinositol (mI) metabolism were measured by magnetic resonance spectroscopy, learning and memory of APP/PS1 mouse was evaluated by the Morris water maze test and the step-down avoidance test, neuron survival number and neuronal structure in the hippocampus were observed by Nissl staining, and BDNF and phosphorylated TrkB detected by Western blot. RESULTS: EA at DU20 acupuncture significantly improve learning and memory in behavioral tests, up-regulate NAA, Glu and mI metabolism, increase the surviving neurons in hippocampus, and promote the expression of BDNF and TrkB in the APP/PS1 transgenic mice. CONCLUSION: These findings suggested that EA is a potential therapeutic for ameliorate cognitive dysfunction, and it might be due to EA could improve NAA and Glu metabolism by upregulation of BDNF in APP/PS1 mice.


Subject(s)
Animals , Male , Mice , Electroacupuncture/methods , Aspartic Acid/analogs & derivatives , Glutamic Acid/metabolism , Hippocampus/chemistry , Learning/physiology , Memory/physiology , Protein-Tyrosine Kinases/analysis , Magnetic Resonance Imaging , Membrane Glycoproteins/analysis , Mice, Transgenic , Magnetic Resonance Spectroscopy , Random Allocation , Blotting, Western , Aspartic Acid/metabolism , Maze Learning , Brain-Derived Neurotrophic Factor , Models, Animal , Exercise Test , Hippocampus/diagnostic imaging , Inositol/analysis
4.
Bauru; s.n; 2017. 112 p. tab, ilus, graf.
Thesis in Portuguese | LILACS, BBO | ID: biblio-880412

ABSTRACT

O objetivo deste estudo consistiu em avaliar a expressão imuno-histoquímica da podoplanina e do CD44v6 pelas células malignas, verificando a associação destas proteínas com as variáveis clínicas, microscópicas, com o índice histopatológico de malignidade e com a sobrevivência livre de doença de 91 pacientes portadores de carcinomas espinocelulares (CEC) de lábio inferior, tratados no Centro de Tratamento e Pesquisa do Hospital do Câncer A.C.Camargo, São Paulo. Os tumores foram corados, separadamente, com os anticorpos anti-podoplanina e anti-CD44v6, sendo avaliada a imunoexpressão destas proteínas pelas células neoplásicas, no front de invasão tumoral, por meio de um método semi-quantitativo de escores. A associação da expressão da podoplanina e do CD44v6 com as variáveis demográficas, clínicas e microscópicas foi feita pelo teste do qui-quadrado ou exato de Fisher. As taxas de sobrevivência livre de doença, acumuladas em cinco e dez anos, foram calculadas pelo teste de Kaplan-Meier e a influência das variáveis clínicas e microscópicas no prognóstico avaliadas pelo modelo de regressão de Cox. A correlação entre a podoplanina e o CD44v6 foi analisada pelo teste de Spearman. Em todos os testes estatísticos utilizou-se um nível de significância de 5%. Os resultados mostraram uma predominância da forte expressão membranosa e citoplasmática da podoplanina pelas células malignas. Verificou-se uma associação significativa da podoplanina citoplasmática com a recidiva locorregional (p=0,028) e da podoplanina membranosa com o índice histopatológico de malignidade tumoral (p=0,026). O CD44v6 foi fortemente expresso pelas células neoplásicas de 95,4% dos CECs e significativamente, associado com o estadiamento clínico T (p=0,034). Não houve correlação entre a podoplanina e o CD44v6 nos CECs de lábio inferior. A forte expressão de podoplanina membranosa (p=0,016) e citoplasmática (p=0,030) pelas células malignas foi fator de prognóstico favorável independente na sobrevivência livre de doença. Concluímos que a podoplanina e o CD44v6 são fortemente expressos pelas células neoplásicas e que a forte imunoexpressão membranosa e citoplasmática da podoplanina pode auxiliar na identificação do risco de recidiva locorregional nos pacientes portadores de carcinoma espinocelular de lábio inferior.(AU)


The aim of this study was evalute the podoplanin and CD44v6 immunohistochemical expression by malignant cells and its association with the clinical and microscopic variables, tumor histopathological grading and disease-free survival of 91 patients with lip squamous cell carcinomas (SCC), submitted to surgical treatment at Research and Treatment Center of the Cancer Hospital A.C. Camargo, São Paulo. The tumors were stained separately, with the antibodies anti-podoplanin and anti-CD44v6, and the immunoexpression of these proteins, by the neoplastic cells in the invasion front, was evaluated by a semi-quantitative scores method. Chi-square test or Fishers exact test was used to analyze the association of podoplanin and CD44v6 expression with demographic, clinical, and microscopic variables. Disease-free survival in five and ten years, were calculated by the Kaplan-Meier method and the influence of clinical and microscopic variables on prognosis were evaluated by the Cox regression model. The correlation between podoplanin and CD44v6 expression was analyzed by Spearman's test and a significance level of 5% was used in all statistical tests. The results showed a predominance of strong membranous and cytoplasmic podoplanin expression by malignant cells. An association between cytoplasmic podoplanin and locorregional recurrence (p=0,028) and membranous podoplanin with tumor histopathological grading (p=0,026). CD44v6 was strongly expressed in 95.4% of the SCCs neoplastic cells and significantly associated with the clinical staging T (p=0,034). There was no correlation between podoplanin and CD44v6 expression in the lower lip SCC. The strong expression of membranous (p=0.016) and cytoplasmic (p=0.030) podoplanin by malignant cells was a favorable independent prognostic factor in disease-free survival. Concluding, the podoplanin and CD44v6 are strongly expressed by neoplastic cells and the strong membranous and cytoplasmic immunoexpression of podoplanin can help the identification of locoregional recurrence risk in patients with squamous cell carcinoma of the lower lip.(AU)


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Carcinoma, Squamous Cell/pathology , Hyaluronan Receptors/analysis , Lip Neoplasms/pathology , Membrane Glycoproteins/analysis , Neoplasm Recurrence, Local/pathology , Age Factors , Biomarkers, Tumor/analysis , Immunohistochemistry , Kaplan-Meier Estimate , Prognosis , Sex Factors , Statistics, Nonparametric
5.
São Paulo; s.n; 2016. 208 p. ilust, tabelas.
Thesis in Portuguese | LILACS, Inca | ID: biblio-1178191

ABSTRACT

O câncer de reto é o segundo tumor mais comum no intestino grosso correspondendo a um terço do total de casos de câncer colorretal (CCR). Pacientes com câncer de reto em estádios II e III são tratados com radioquimioterapia neoadjuvante seguida de ressecção cirúrgica do tumor. Análises das peças cirúrgicas ressecadas mostraram que apenas 10-45% dos pacientes obtém resposta patológica completa (RCp) à terapia neoadjuvante, estando essa associada com uma diminuição da recorrência local, melhora da sobrevida livre de doença e aumento na preservação esfincteriana. Apesar da melhora na sobrevida nas últimas décadas, a resposta à terapia neoadjuvante continua variável e imprevisível e não é possível identificar e separar clinicamente os grupos de pacientes que terão ou não resposta completa ao tratamento neoadjuvante. Além disso, os mecanismos de resistência à radioquimioterapia nos tumores de reto são pouco compreendidos. Dessa forma, o objetivo principal deste estudo foi identificar marcadores e mecanismos celulares relacionados à resistência à terapia neoadjuvante em adenocarcinoma de reto e o papel das vesículas extracelulares (VEs) nesse processo. O estudo proteômico comparativo entre biópsias obtidas de tumores pré-tratamento com o tumor residual removido cirurgicamente pós-tratamento radioquimioterápico mostrou uma importante alteração no perfil de expressão proteica. Entre as proteínas que aumentam a expressão após a neoadjuvância estão as proteínas de reparo de dano de DNA, Ku70 e Ku80, e a proteína de tráfego intracelular Rab5C. Em um modelo in vitro, foi demonstrado que Rab5C orquestra um mecanismo de resistência à radioterapia nos tumores de reto através da modulação da internalização de EGFR promovida por radiação ionizante (RI). O EGRF intracelular por sua vez é essencial para regular a expressão de Ku70 e Ku80 e a resistência celular à RI. Estes dados apontam Rab5C e EGFR como potenciais alvos terapêuticos para sensibilizar células de câncer de reto resistentes ao tratamento neoadjuvante. Também foi observado que a RI promove alterações epigenéticas predominantemente de hipometilação, e entre os genes alterados estão SPG20 e TBC1D16, sendo o primeiro importante para a internalização de EGFR e o segundo para a regulação de Rab5C e modulação de EGFR. O perfil de expressão proteica foi ainda comparado entre biópsias pré-tratamento de pacientes com RCp e sem resposta patológica, e o resultado mostrou que esses dois grupos de pacientes apresentam um diferente perfil de expressão proteica. Nos pacientes com RCp as proteínas com aumento da expressão estão atuando em vias que favorecem a resposta à terapia, como a detoxificação de glutationa e degradação de glicogênio, enquanto as proteínas com aumento da expressão em pacientes sem RCp estão envolvidas em vias do metabolismo energético do tumor as quais contribuem para a resistência tumoral à terapia. As diferenças observadas nestes grupos devem ser amplamente exploradas uma vez que podem ser marcadores preditivos de resposta ao tratamento radioquimioterápico. A realização de estudos funcionais foi viabilizada pela geração de um modelo celular de tumor de reto resistente à radioterapia. Ao analisar as VEs secretadas por estas células foi observado que a RI não altera a quantidade e o tamanho médio das VEs secretadas, porém é capaz de alterar o carregamento proteico das mesmas. De fato, as VEs de células irradiadas apresentam um perfil proteico diferente quando comparadas as VEs de células não irradiadas, onde encontramos aumento da expressão de Ku70, Ku80 e Rab5C, além das metiltransferases NSUN2 e GLYM nas VEs de células pós RI. Interessantemente, as VEs secretadas por células irradiadas são capazes de transmitir a resistência à RI às células não irradiadas. Além disso os resultados mostraram que o tratamento com VEs de células irradiadas promove metilação em 98% do DNA avaliado em células SW837 em comparação ao tratamento com VEs de células não irradiadas. Os genes hipermetilados estão envolvidos em vias relacionadas ao sistema imune, como a apresentação de antígeno, sinalização de imunodeficiência primária e maturação de células dendríticas. Por fim, foi identificado que a expressão da proteína A33 está relacionada ao grau de diferenciação dos tumores colorretais, e que essa proteína está presente em VEs secretadas por células de adenocarcinoma de reto, indicando que a mesma pode ser usada para isolar VEs específicas do tecido colorretal. Os dados obtidos neste trabalho apontam mecanismos relacionados à resistência à terapia neoadjuvante no adenocarcinoma de reto e que em conjunto permitirão identificar novos alvos terapêuticos com potencial de melhorar a resposta à radioquimioterapia, além de identificar marcadores de resposta à terapia neoadjuvante antes do tratamento e dessa forma, poupar os pacientes não respondedores de terapias tóxicas e melhorar a sustentabilidade na saúde poupando os custos com drogas não eficientes para um grupo de pacientes.


Rectal cancer is the second most common cancer in large intestine, corresponding to one third of total cases of colorectal cancer (CRC). Patients with rectal cancer in stage II and III are treated with neoadjuvant chemoradiation followed by surgical resection. Analyzes of the resected tumor demonstrated that only 10-45% of the patients achieve pathological complete response (pCR) after neoadjuvant therapy, which is associated with a decrease in local recurrence, improvement of disease free survival and increase in sphincter preservation. Despite the improvement in survival in the last decades, the response to neoadjuvant therapy is still variable and unpredictable, and before the surgery it is not possible to identify and separate clinically the group of patients that will or will not have complete response to neoadjuvant treatment. Moreover, the mechanisms of resistance of rectal tumors to chemoradiation are poorly understood. Thus, the main objective of this work was to identify biomarkers and cellular mechanisms related to the resistance to neoadjuvant therapy in rectal adenocarcinomas and the role of extracellular vesicles (EVs) in this process. The comparative proteomic study between biopsy obtained from tumors pretreatment with residual tumor, post chemoradiation treatment, removed by surgery showed an important alteration in the protein expression profile. Among the proteins with increased expression after neoadjuvant therapy are the DNA repair proteins Ku70 and Ku80, and the protein involved in the intracellular trafficking, Rab5C. It was demonstrated in vitro that Rab5C orchestrates a mechanism of radioresistance in rectal tumors by modulating the EGFR internalization promoted by ionizing radiation (IR). The intracellular EGFR is essential to regulate Ku70 and Ku80 expression and the cell resistance to IR. These data pointed Rab5C and EGFR as potential therapeutic targets to sensitize rectal cancer cells resistant to neoadjuvant treatment. It was also observed that IR promotes epigenetic alterations, predominantly hypomethylation, and between the altered genes are SPG20 and TBC1D16, the first is important to EGFR internalization, while the second regulates Rab5C and modulates EGFR. The protein expression profile was further compared between biopsy pretreatment of patients with and without pCR, and the results showed that these two groups of patients present a different protein expression profile. In patients with pCR the proteins with increased expression are involved in pathways favoring the response to therapy, as glutathione-mediated detoxification and glycogen degradation, while the proteins with increased expression in patients without pCR are involved in tumor energetic metabolism pathways that contribute to tumor resistance to therapy. The observed differences in these groups should be widely explored since they may be predictive markers of response to chemoradiation treatment. The performance of functional studies was possible by generation of a cellular model of rectal tumor resistant to radiotherapy. The analysis of the EVs secreted by these cells showed that IR does not alter the amount and the medium size of secreted EVs, but is able to change their protein content. EVs from irradiated cells presented a different protein profile when compared to EVs from non-irradiated cells, where it was found the increased expression of Ku70, Ku80 and Rab5C, besides the methyltransferases NSUN2 and GLYM in EVs after irradiation. Interestingly, the EVs secreted by irradiated cells are capable of transfering resistance to IR to non-irradiated cells. Moreover, the results showed that the treatment of SW837 cells with EVs from irradiated cells promoted methylation in 98% of the analyzed DNA in comparison with the treatment with EVs from non-irradiated cells. The hypermethylated genes are involved in pathways related to immune system, as antigen presentation, primary immunodeficiency signaling and dendritic cells maturation. Lastly, it was identified that the A33 expression is related to the colorectal tumors differentiation degree, and this protein is present in EVs secreted by rectal adenocarcinoma, indicating that it may be used to isolate EVs specific from colorectal tissues. The data obtained in this work pointed to mechanisms related to resistance to neoadjuvant therapy in rectal adenocarcinoma that together will allow to identify new therapeutic targets with the potential to improve the response to chemoradiation, as well as to identify markers of response to neoadjuvant therapy before the treatment, and, in this way, avoid the non-responder patients to receive toxic therapies and improve health sustainability, sparing cost with non-efficient drugs for a group of patients.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Neoadjuvant Therapy , Extracellular Vesicles/pathology , Rectal Neoplasms/genetics , Membrane Glycoproteins/analysis , Biomarkers , Adenocarcinoma/genetics , Proteins/analysis , Gene Expression , Cell Line , Cell Survival , Treatment Outcome , Genes, erbB-1 , Cell Proliferation , Extracellular Vesicles/genetics , Methylation , Neoplasm Invasiveness
6.
Acta cir. bras ; 30(9): 604-610, Sep. 2015. ilus
Article in English | LILACS | ID: lil-761496

ABSTRACT

PURPOSE: This study was conducted to investigate the effect of normal mesenteric lymph (NML) from mice on the spleen injury induced by lipopolysaccharide (LPS) challenge.METHODS: Mice in the LPS and LPS+NML groups received an intraperitoneal injection of LPS (35 mg/kg) and kept for 6 h.. The mice in the LPS+NML group received NML treatment at 1 h after LPS injection. Afterward, the splenic morphology, the levels of lipopolysaccharide-binding protein (LBP), cluster of differentiation 14 (CD14), phosphorylation mitogen-activated protein kinases (MAPKs), and inflammatory mediators in splenic tissue were investigated.RESULTS:LPS injection induced spleen injury, increased the levels of LBP, CD14, tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interferon γ (IFN-γ), and decreased the IL-4 content in the spleen. By contrast, NML treatment reversed these changes. Meanwhile, the LPS challenge decreased the phosphorylation levels of p38 MAPK, extracellular regulated protein kinases 1/2, and c-Jun N-terminal kinase (JNK). Moreover, the phosphorylation levels of p38 MAPK and JNK were further decreased by the NML administration.CONCLUSION:rRdThe normal mesenteric lymph treatment alleviated lipopolysaccharide induced spleen injury by attenuating LPS sensitization and production of TNF-α, IL-6, and IFN-γ.


Subject(s)
Animals , Lipopolysaccharides/administration & dosage , Lymph Nodes/transplantation , Mesentery , Splenic Diseases/therapy , Acute-Phase Proteins/analysis , /analysis , Carrier Proteins/analysis , Cytokines/analysis , Enzyme-Linked Immunosorbent Assay , Injections, Intraperitoneal , Mice, Inbred BALB C , Membrane Glycoproteins/analysis , Mitogen-Activated Protein Kinase Kinases/analysis , Random Allocation , Reproducibility of Results , Treatment Outcome
8.
Clinics ; 69(10): 660-665, 10/2014. tab, graf
Article in English | LILACS | ID: lil-730460

ABSTRACT

OBJECTIVE: Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2. .


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Young Adult , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/secondary , Lymphatic Vessels/pathology , Ovarian Neoplasms/pathology , Adenocarcinoma, Mucinous/chemistry , /analysis , Diagnosis, Differential , Immunohistochemistry , Keratins/analysis , Lymphatic Metastasis , Lymphatic Vessels/chemistry , Membrane Glycoproteins/analysis , Membrane Proteins/analysis , Mucins/analysis , Ovarian Neoplasms/chemistry , Reference Values , Tissue Array Analysis , Tumor Burden , Biomarkers, Tumor/analysis
9.
Braz. j. phys. ther. (Impr.) ; 18(6): 538-543, 09/01/2015. tab, graf
Article in English | LILACS | ID: lil-732351

ABSTRACT

BACKGROUND: The adapted arcometer has been validated for use in adults. However, its suitability for use in children can be questioned given the structural differences present in these populations. OBJECTIVE: To verify the concurrent validity, repeatability, and intra- and inter-reproducibility of the adapted arcometer for the measurement of the angles of thoracic kyphosis and lumbar lordosis in children. METHOD: Forty children were evaluated using both sagittal radiography of the spine and the adapted arcometer. The evaluations using the arcometer were carried out by two trained evaluators on two different days. In the statistical treatment, the intraclass correlation coefficient (ICC), Pearson's product moment correlation, Spearman's rho, the paired t test, and Wilcoxon's test were used (α=.05). RESULTS: A moderate and significant correlation was found between the x-ray and the adapted arcometer regarding thoracic kyphosis, but no correlation was found regarding lumbar lordosis. Repeatability and intra-evaluator reproducibility of the thoracic kyphosis and lumbar lordosis were confirmed, which was not the case of inter-evaluator reproducibility. CONCLUSION: The adapted arcometer can be used to accompany postural alterations in children made by the same evaluator, while its use for diagnostic purposes and continued evaluation by different evaluators cannot be recommended. Further studies with the aim of adapting this instrument for use in children are recommended. .


Subject(s)
Bacterial Proteins/analysis , Membrane Glycoproteins/analysis , Membrane Glycoproteins/genetics , Prodigiosin/biosynthesis , Serratia marcescens/metabolism , Centrifugation, Density Gradient , Electrophoresis, Polyacrylamide Gel , Molecular Weight , Membrane Glycoproteins/biosynthesis , Solubility , Sarcosine/analogs & derivatives , Serratia marcescens/analysis
10.
Acta cir. bras ; 29(9): 544-552, 09/2014. graf
Article in English | LILACS | ID: lil-722131

ABSTRACT

PURPOSE: To evaluate the effects of sucralfate on tissue content of neutral and acids mucins in rats with diversion colitis. METHODS: Thirty-six rats were submitted to a proximal right colostomy and a distal mucous fistula. They were divided into two groups according to sacrifice to be performed two or four weeks after intervention. Each group was divided into three subgroups according daily application of enemas containing saline, sucralfate at 1.0 g/kg/day or 2.0 g/kg/day. Colitis was diagnosed by histological analysis and neutral and acid mucins by Periodic Acid Schiff and Alcian Blue techniques, respectively. The contents of mucins were quantified by computer-assisted image analysis. Student's t paired and ANOVA test were used to compare the contents of both types of mucins among groups, and to verify the variance with time, establishing level of signification of 5% for both (p<0.05). RESULTS: Enemas containing sucralfate improves the inflammation and increases the tissue contents of neutral and acid mucins. The content of neutral mucins does not change with the time or concentration of sucralfate used, while acid mucins increases with concentration and time of intervention. CONCLUSIONS: Sucralfate enemas improve the inflammatory process and increase the tissue content of neutral and acid mucins in colon without fecal stream. .


Subject(s)
Animals , Male , Anti-Ulcer Agents/therapeutic use , Colitis/drug therapy , Enema/methods , Membrane Glycoproteins/analysis , Mucins/analysis , Sucralfate/therapeutic use , Anti-Ulcer Agents/pharmacology , Colitis/pathology , Colon/drug effects , Colon/pathology , Disease Models, Animal , Image Processing, Computer-Assisted , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Mucins/drug effects , Rats, Wistar , Reproducibility of Results , Sucralfate/pharmacology , Time Factors , Treatment Outcome
11.
Acta cir. bras ; 29(6): 359-364, 06/2014. graf
Article in English | LILACS | ID: lil-711592

ABSTRACT

PURPOSE: To determine the role of mesenteric lymph reperfusion (MLR) on endotoxin translocation in brain to discuss the mechanism of brain injury subjected to superior mesenteric artery occlusion (SMAO) shock. METHODS: Twenty-four rats were randomly assigned to MLR, SMAO, MLR+SMAO and sham groups. MLR was performed by clamping the mesenteric lymph duct (MLD) for 1 h and then allowing reperfusion for 2 h in the MLR group; SMAO involved clamping the superior mesenteric artery (SMA) for 1 h, followed by reperfusion for 2 h in the SMAO group; occlusion of both the SMA and MLD for 1 h was followed by reperfusion for 2 h in the MLR+SMAO group rats. RESULTS: SMAO shock induced severe increased levels of the endotoxin, lipopolysaccharide receptor, lipopolysaccharide-binding protein, intercellular adhesion molecule-1 and tumor necrosis factor-α. Concurrently, MLR after SMAO shock further aggravates these deleterious effects. CONCLUSION: Mesenteric lymph reperfusion exacerbated the endotoxin translocation in brain; thereby increased inflammatory response occurred, suggesting that the intestinal lymph pathway plays an important role in the brain injury after superior mesenteric artery occlusion shock. .


Subject(s)
Animals , Male , Bacterial Translocation/physiology , Brain Injuries/etiology , Endotoxins/physiology , Lymphatic Vessels/physiology , Mesentery , Mesenteric Vascular Occlusion/physiopathology , Reperfusion Injury/physiopathology , Acute-Phase Proteins/analysis , /analysis , Brain Injuries/metabolism , Carrier Proteins/analysis , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Endotoxins/analysis , Intercellular Adhesion Molecule-1/analysis , Ligation , Lymphatic Vessels/surgery , Mesenteric Artery, Superior , Membrane Glycoproteins/analysis , Mesenteric Vascular Occlusion/complications , Random Allocation , Rats, Wistar , Reperfusion Injury/complications , Time Factors , Tumor Necrosis Factor-alpha/analysis
12.
Braz. j. med. biol. res ; 47(5): 376-383, 02/05/2014. graf
Article in English | LILACS | ID: lil-709439

ABSTRACT

The intestinal lymph pathway plays an important role in the pathogenesis of organ injury following superior mesenteric artery occlusion (SMAO) shock. We hypothesized that mesenteric lymph reperfusion (MLR) is a major cause of spleen injury after SMAO shock. To test this hypothesis, SMAO shock was induced in Wistar rats by clamping the superior mesenteric artery (SMA) for 1 h, followed by reperfusion for 2 h. Similarly, MLR was performed by clamping the mesenteric lymph duct (MLD) for 1 h, followed by reperfusion for 2 h. In the MLR+SMAO group rats, both the SMA and MLD were clamped and then released for reperfusion for 2 h. SMAO shock alone elicited: 1) splenic structure injury, 2) increased levels of malondialdehyde, nitric oxide (NO), intercellular adhesion molecule-1, endotoxin, lipopolysaccharide receptor (CD14), lipopolysaccharide-binding protein, and tumor necrosis factor-α, 3) enhanced activities of NO synthase and myeloperoxidase, and 4) decreased activities of superoxide dismutase and ATPase. MLR following SMAO shock further aggravated these deleterious effects. We conclude that MLR exacerbates spleen injury caused by SMAO shock, which itself is associated with oxidative stress, excessive release of NO, recruitment of polymorphonuclear neutrophils, endotoxin translocation, and enhanced inflammatory responses.


Subject(s)
Animals , Male , Lymph/metabolism , Mesenteric Vascular Occlusion/complications , Reperfusion Injury/etiology , Reperfusion/adverse effects , Spleen/injuries , Acute-Phase Proteins/analysis , Adenosine Triphosphatases/analysis , /analysis , Carrier Proteins/analysis , Endotoxins/analysis , Intercellular Adhesion Molecule-1/analysis , Intestines/blood supply , Mesenteric Artery, Superior , Malondialdehyde/analysis , Membrane Glycoproteins/analysis , Nitric Oxide Synthase/analysis , Nitric Oxide/analysis , Peroxidase/analysis , Rats, Wistar , Spleen/pathology , Superoxide Dismutase/analysis , Tumor Necrosis Factor-alpha/analysis
15.
Säo Paulo med. j ; 129(6): 402-409, Dec. 2011. ilus, tab
Article in English | LILACS | ID: lil-611808

ABSTRACT

CONTEXT AND OBJECTIVE: Dendritic cell maturation is considered essential for starting an immune response. The CD83 antigen is an important marker of dendritic cell maturation. The objectives here were to analyze CD83 antigen expression in human breast fibroadenoma and breast tissue adjacent to the lesion and to identify clinical factors that might influence this expression. DESIGN AND SETTING: This was a retrospective study at a public university hospital, in which 29 histopathological samples of breast fibroadenoma and adjacent breast tissue, from 28 women of reproductive age, were analyzed. METHODS: The immunohistochemistry method was used to analyze the cell expression of the antigen. The antigen expression in the cells was evaluated by means of random manual counting using an optical microscope. RESULTS: Positive expression of the CD83 antigen in the epithelial cells of the fibroadenoma (365.52; standard deviation ± 133.13) in relation to the adjacent breast tissue cells (189.59; standard deviation ± 140.75) was statistically larger (P < 0.001). Several clinical features were analyzed, but only parity was shown to influence CD83 antigen expression in the adjacent breast tissue, such that positive expression was more evident in nulliparous women (P = 0.042). CONCLUSIONS: The expression of the CD83 antigen in the fibroadenoma was positive and greater than in the adjacent breast tissue. Positive expression of the antigen in the adjacent breast tissue was influenced by parity, and was significantly more evident in nulliparous women.


CONTEXTO E OBJETIVOS: A maturação da célula dendrítica é considerada essencial para o início da resposta imune. O antígeno CD83 é um importante marcador da maturação da célula dendrítica. Os objetivos são analisar a expressão do antígeno CD83 no fibroadenoma mamário humano e no tecido mamário adjacente à lesão e identificar fatores clínicos que possam influenciar esta expressão. TIPO DE ESTUDO E LOCAL: Este é um estudo retrospectivo, realizado em um hospital público universitário, onde 29 amostras histopatológicas de fibroadenomas de mamas e de tecidos mamários adjacentes, de 28 mulheres em idade reprodutiva, foram analisados. MÉTODOS: O método de imunoistoquímica foi utilizado na análise da expressão celular do antígeno. A expressão do antígeno nas células foi avaliada por contagem aleatória e manual utilizando-se microcópio de luz. RESULTADOS: A expressão positiva do antígeno CD83 nas células epiteliais dos fibroadenomas (365,52; desvio padrão ± 133,13) em relação às células do tecido mamário adjacente (189,59; desvio padrão ± 140,75) foi estatisticamente superior (P < 0,001). Vários aspectos clínicos foram analisados, porém, a paridade se mostrou influente na expressão do antígeno CD83 no tecido mamário adjacente, onde a expressão positiva foi mais evidente nas mulheres nulíparas (P = 0,042). CONCLUSÕES: A expressão do antígeno CD83 foi positiva e mais expressiva no fibroadenoma do que no tecido mamário adjacente. A expressão positiva do antígeno no tecido mamário adjacente foi influenciada pela paridade, sendo significativamente mais evidente nas mulheres nulíparas.


Subject(s)
Adolescent , Adult , Female , Humans , Middle Aged , Young Adult , Antigens, CD/analysis , Antigens, Neoplasm/analysis , Breast Neoplasms/immunology , Breast/immunology , Fibroadenoma/immunology , Immunoglobulins/analysis , Membrane Glycoproteins/analysis , Breast Neoplasms/pathology , Breast/pathology , Fibroadenoma/pathology , Retrospective Studies
16.
Clinics ; 65(12): 1279-1283, 2010. ilus, tab
Article in English | LILACS | ID: lil-578565

ABSTRACT

OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2-40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6 percent) cases, with 29/31 (93.5 percent) of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node-positive cases was lower than that of node-negative (18.9 percent vs. 22.6 percent, respectively). Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5 percent vs. 21.6 percent, respectively. In 27/143 (18.8 percent) cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5 percent vs. 3.7 percent, respectively), although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host-tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.


Subject(s)
Female , Humans , Middle Aged , Carcinoma, Adenosquamous/metabolism , Carcinoma, Adenosquamous/secondary , Membrane Glycoproteins/analysis , Biomarkers, Tumor/metabolism , Uterine Cervical Neoplasms/metabolism , Analysis of Variance , Fibroblasts/metabolism , Fibroblasts/pathology , Lymphatic Metastasis , Prognosis , Retrospective Studies , Uterine Cervical Neoplasms/pathology
17.
Medicina (B.Aires) ; 68(2): 147-150, mar.-abr. 2008. ilus
Article in Spanish | LILACS | ID: lil-633530

ABSTRACT

La neoplasia hematodérmica CD4+ CD56+ con fenotipo de célula dendrítica plasmocitoide es una rara y agresiva neoplasia recientemente reconocida por la WHO-EORTC classification. Afecta adultos de edad media y ancianos, siendo muy pocos los casos descriptos en niños. Presentamos el caso de una niña de 12 años con grave retraso mental, estigmas genéticos y múltiples lesiones cutáneas localizadas en miembros inferiores y superiores. Histológicamente se observó un infiltrado dérmico difuso de células pequeñas y medianas con expresión de CD4, CD56, CD43 y S100 así como de marcadores dendríticos plasmocitoides: CD 123 y BDCA-2 confirmados por citometría de flujo, sin compromiso de sangre periférica ni médula ósea. Cumpliendo dos semanas de tratamiento para leucemia linfoblástica aguda evolucionó con remisión clínica de las lesiones cutaneas.


Hematodermic CD4+ CD56+ neoplasm with plasmacytoid dendritic cell phenotype is a rare and aggressive neoplasm recently recognized by the WHO-EORTC classification. It generally appears in elderly adults, exceptionally in childhood. We present a 12-year-old girl with severe mental retardation, genetic clinical features and multiple nodular cutaneous lesions on legs and arms. Histologically the nodules showed diffuse dermal infiltrate of medium and small cells and expression of CD4, CD56, CD43, S100 and plasmacytoid dendritic markers: CD123, BDCA-2 under flow cytometry study. Peripheral blood and bone marrow were not involved. Clinical remission of cutaneous lesions was observed after two weeks of acute lymphoblastic leukemia therapy.


Subject(s)
Child , Female , Humans , Biomarkers, Tumor , Lymphoma/pathology , Skin Neoplasms/pathology , Diagnosis, Differential , Dendritic Cells/immunology , Dendritic Cells/pathology , Flow Cytometry , /analysis , Killer Cells, Natural/immunology , Lectins, C-Type/analysis , Lymphoma/immunology , Membrane Glycoproteins/analysis , Receptors, Immunologic/analysis , Skin Neoplasms/immunology
18.
Neurol India ; 2001 Mar; 49(1): 19-24
Article in English | IMSEAR | ID: sea-121562

ABSTRACT

Abnormalities of dystrophin are a common cause of muscular dystrophy and testing for dystrophin gene or protein has become a part of routine diagnostic evaluation of patients who present with progressive proximal muscle weakness, high serum creatine kinase concentrations, and histopathological evidence of a dystrophic process. Patients who have no dystrophin abnormalities are assumed to have autosomal recessive muscular dystrophy. In a family consisting of 5 sibs, 2 mentally normal brothers presented with abnormal gait and protrusion of chest and hips. Muscle biopsy from one of them showed dystrophic changes and reduced patchy binding of dystrophin. No detectable deletion was observed in the patient's DNA and his brother with cDMD probes. Dystrophin associated proteins, beta-dystroglycan showed discontinuous immunostaining in the sarcolemma and alpha-sarcoglycan (adhalin) was totally absent, while beta-, gamma-, and delta-sarcoglycans were highly reduced. Immunoblot analysis showed dystrophin of normal molecular weight but of decreased quantity, beta-dystroglycan was reduced by about 37% while alpha-sarcoglycan was completely absent. This study is a first attempt for a systematic clinical, genetic and molecular investigation of the autosomal recessive LGMD in India.


Subject(s)
Adolescent , Cytoskeletal Proteins/analysis , Dystroglycans , Dystrophin/analysis , Genes, Recessive , Humans , Immunohistochemistry , Male , Membrane Glycoproteins/analysis , Muscle, Skeletal/chemistry , Muscular Dystrophies/genetics , Sarcoglycans
19.
Säo Paulo med. j ; 117(4): 145-50, July 1999.
Article in English | LILACS | ID: lil-247138

ABSTRACT

OBJECTIVE: To correlate spleen function with soluble transferrin receptor (sTfR) levels and red cell ferritin (RCF) values in patients with sickle cell diseases. DESIGN: Prospective study. LOCATION: University Hospital, School of Medical Sciences, State University of Campinas; a tertiary hospital. PARTICIPANTS: 60 patients with sickle cell diseases, in a steady state, who had not received blood transfusions for 3 months; 28 normal individuals with no clinical or laboratory signs of anemia. MEASUREMENTS: Determination of serum iron, transferrin iron-binding capacity, serum ferritin, RCF and sTfR. Evaluation of spleen function: erythrocytes with pits were quantified. RESULTS: Patients with sickle cell anemia had sTfR levels significantly higher than in normal individuals or those with HbSC (p=0.0001) and there was an inverse correlation between sTfR and fetal Hb (p=0.0016). RCF values were significantly higher in sickle cell anemia patients than in normal individuals or those with HbSC (p=0.0001), and there was a correlation between RCF and pitted erythrocytes (p=0.0512). CONCLUSION: The association between sTfR and fetal Hb confirms the contribution of fetal Hb to improving the hemolytic state by minimizing the consequent reactive erythrocyte expansion. High sTfR levels are not related to the degree of spleen function deficiency seen in sickle cell disease patients. The deficiency in the exocytosis process of the spleen occurring in sickle cell anemia patients may contribute to their accumulation of RCF


Subject(s)
Humans , Anemia, Sickle Cell/blood , Receptors, Transferrin/blood , Spleen/physiopathology , Anemia, Sickle Cell/physiopathology , Erythrocyte Count , Erythrocytes/ultrastructure , Iron/metabolism , Membrane Glycoproteins/analysis
20.
Rev. mex. reumatol ; 11(2): 42-51, mar.-abr. 1996. tab, ilus
Article in Spanish | LILACS | ID: lil-208135

ABSTRACT

Los antígenos de diferenciación leucocitaria son moléculas que se detectan en la membrana de las células derivadas de la médula ósea y que se expresan con un patrón característico en cada una de las subpoblaciones de leucocitos, en sus variados estadios de diferenciación celular. En la práctica diaria, los antígenos de diferenciación leucocitaria son detectados con el empleo de anticuerpos monoclonales de origen murino; con el uso de diversas técnicas de laboratorio y estos anticuerpos, es factible el detectar, cuantificar, aislar y eliminar subpoblaciones definidas de células, tanto in vivo como in vitro. El conocimiento actual de los antígenos de diferenciación leucocitaria ha tenido un gran impacto en el campo de la reumatología, ya que ha facilitado grandemente el estudio de la fisiopatología de diversas enfermedades reumáticas, principalmente las de origen autoinmune. Además, los anticuerpos dirigidos en contra de los antígenos de diferenciación leucocitaria pueden ser de gran utilidad en el seguimiento y terapia de diversas condiciones caracterizadas por la presencia de inflamación y daño a tejidos


Subject(s)
Antibodies, Monoclonal , Antigens, CD/physiology , Rheumatic Diseases/physiopathology , Membrane Glycoproteins/analysis , Immune System/cytology , Leukocytes/physiology , Cytological Techniques/standards
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