RESUMO
INTRODUCTION: In response to the COVID-19 pandemic, various candidate vaccines has been approved to be used by WHO. However, there is low adherence to the vaccination campaign, especially in Mali. The goal was to study the perception of fourth municipality's population of the district of Bamako, about the COVID-19 vaccine. METHODS: It was a cross-sectional descriptive and analytic study conducted from May to August 2021. A rational selection of two wards of the fourth municipality of Bamako was carried out. The Chi-square test of Pearson was used to test association between variables. RESULTS: In total 179 people from two wards were surveyed. The average age was 37.73 years (SD=13.67), 34.6% (n=62) we'renot in school, and 7.8% (n=62) had received at least the first dose of a COVID-19 vaccine. 37.4% (n=67) did not believe in the existence of COVID-19; while 84.9% (n=152) didn't know at least the name of the vaccine in use in Mali. 65.4% (n=117) didn't trust the vaccine, while 78.1% (n=25) would have preferred other vaccines from AstraZeneca. Knowledge of the vaccine was associated with education level (OR=18.86; 95% CI [7.16-49.64]; p=0.00). CONCLUSION: The population of the fourth municipality of Bamako have a few knowledge about the vaccine in use in Mali. So it's necessary to strengthen awareness campaigns.
INTRODUCTION: Face à la pandémie de la COVID-19, plusieurs vaccins candidats ont reçu l'accord de l'OMS d'être utilisés. Cependant on assiste à une faible adhésion à la campagne de vaccination, surtout au Mali. L'objectif était d'étudier la perception de la population de la commune IV du district de Bamako sur le vaccin contre la COVID-19. MÉTHODE: Il s'agissait d'une étude transversale descriptive et analytique, réalisée du mois de Mai au mois d'Août 2021. Un choix raisonné de deux quartiersde la commune IVa été réalisé. Le test de Khi-deux de Pearson a été utilisé pour vérifier l'association entre les variables. RÉSULTATS: Au total179 personnes de deux quartiers de la commune IV ont été enquêtées. L'âge moyen était 37,73 ans (SD=13,67), 34,6% (n=62) n'étaient pas scolarisées, et 7,8% (n=62) avaient reçu au moins la première dose d'un vaccin contre la COVID-19.37,4% (n=67) ne croyaient pas à l'existence de la COVID-19 ; pendant que 84,9% (n=152)ne connaissaient,ne seraitce que le nom du vaccin en usage au Mali. 65,4% (n=117) ne faisaient pas confiance au vaccin, pendant que 78,1% des enquêtés (n=25) auraient préféré autres vaccins différents d'AstraZeneca. On pouvait voir que La connaissance du vaccin étaitassociée au niveau d'étude (OR=18,86 ; 95% IC [7,16-49,64] ; p=0,00). CONCLUSION: La population de la commune IV du district de Bamako a très peu de connaissance sur le vaccin utilisé au Mali, d'où la nécessité de renforcer les campagnes de sensibilisation.
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Skeletal muscle is under inhibitory homeostatic regulation by multiple ligands of the transforming growth factor-ß (TGFß) superfamily. Follistatin is a secreted protein that promotes muscle growth and function by sequestering these ligands extracellularly. In the present study, we evaluated the potential of ACE-083 - a locally acting, follistatin-based fusion protein - as a novel therapeutic agent for focal or asymmetric myopathies. Characterization of ACE-083 in vitro revealed its high affinity for heparin and extracellular matrix while surface plasmon resonance and cell-based assays confirmed that ACE-083 binds and potently neutralizes myostatin, activin A, activin B and growth differentiation factor 11 (GDF11). Intramuscular administration of ACE-083 caused localized, dose-dependent hypertrophy of the injected muscle in wild-type mice and mouse models of Charcot-Marie-Tooth disease (CMT) and Duchenne muscular dystrophy, with no evidence of systemic muscle effects or endocrine perturbation. Importantly, ACE-083 also increased the force of isometric contraction in situ by the injected tibialis anterior muscle in wild-type mice and disease models and increased ankle dorsiflexion torque in CMT mice. Our results demonstrate the potential of ACE-083 as a therapeutic agent for patients with CMT, muscular dystrophy and other disorders with focal or asymmetric muscle atrophy or weakness.
Assuntos
Doença de Charcot-Marie-Tooth/tratamento farmacológico , Folistatina/farmacologia , Músculo Esquelético/efeitos dos fármacos , Distrofia Muscular de Duchenne/tratamento farmacológico , Proteínas Recombinantes de Fusão/farmacologia , Ativinas/metabolismo , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Doença de Charcot-Marie-Tooth/patologia , Modelos Animais de Doenças , Folistatina/genética , Folistatina/uso terapêutico , Fatores de Diferenciação de Crescimento/metabolismo , Humanos , Hipertrofia/induzido quimicamente , Ligantes , Masculino , Camundongos , Camundongos Endogâmicos mdx , Força Muscular/efeitos dos fármacos , Músculo Esquelético/patologia , Distrofia Muscular de Duchenne/patologia , Miostatina/metabolismo , Receptores de IgG/genética , Receptores de IgG/uso terapêutico , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/uso terapêuticoRESUMO
Clinical and pathological studies of cutaneous T-cell lymphomas (CTCL) reveal variations in tumor cell morphology and surface membrane phenotype that are of diagnostic and prognostic importance. Our study investigates blastic transformation and surface antigen change on CTCL cells in vitro under the influence of tumor-promoting phorbol ester (TPA) and phytohemagglutinin. Both agents transformed tumor cells with cerebriform nuclei into blast cells within 5 days; however, Sézary cells were somewhat resistant to transformation with phytohemagglutinin. Multinucleated cells with prominent nucleoli resembled Reed-Sternberg cells of Hodgkin's disease. These morphological changes simulated the appearance of the aggressive tumor stage of mycosis fungoides. During blastic transformation, the erythrocyte rosette receptor was induced by TPA on sheep erythrocyte-rosette-negative Sézary cells from one patient. During the first 24 hr in vitro, Sézary and MF cells stimulated by TPA lost Leu 3a (T4) antigen while maintaining original high levels of Leu 1 antigen. In contrast, leukemia cells from patients with adult T-cell leukemia (ATL) were resistant to modulation of Leu 3a antigen by TPA; 3A1 antigen on CTCL and ATL cells was unaffected by TPA. Blastic transformation of CTCL cells was observed with both TPA and phytohemagglutinin, but helper T-cell antigen Leu 3a (T4) and erythrocyte rosette receptor changes occurred only with TPA. Thus, blastic transformation and surface differentiation were not directly related. These results provide a possible model for the study of blastic transformation and surface antigen/receptor variation in CTCL. They also may provide an independent test for the distinction of CTCL and ATL in vitro. Finally, they illustrate the relative resistance of ATL to surface antigen modulation as previously shown for Tac antigen modulation by anti-Tac antibody.
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Antígenos de Superfície/análise , Leucemia/fisiopatologia , Micose Fungoide/fisiopatologia , Forbóis/toxicidade , Síndrome de Sézary/fisiopatologia , Linfócitos T/fisiologia , Acetato de Tetradecanoilforbol/toxicidade , Adulto , Transformação Celular Neoplásica , Células Cultivadas , Humanos , Cinética , Leucemia/imunologia , Micose Fungoide/imunologia , Fenótipo , Síndrome de Sézary/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
In this study the authors attempted to establish immunopathologic criteria for the distinction of various T-cell lymphomas affecting the skin. We studied skin specimens from 27 patients with mycosis fungoides (MF) (n = 12), the Sézary syndrome (SS) (n = 6), adult T-cell leukemia (ATL) (n = 4), and nonepidermotropic T-cell lymphoma of large cell (n = 4) and lymphoblastic (n = 1) types. Identification of tumor cells in mixed cell populations and detection of weak expression of surface antigens by tumor cells was facilitated by immunoelectron microscopy. The mature helper T-cell phenotype (T11+ T3+ T4+) was found in 14 of 18 cases of MF/SS. One case of MF had a cytotoxic/suppressor (T4- T8+ 3A1+) phenotype; one with frequent blastic cells showed only weak expression of T4 antigen; 2 cases of SS were T11-. Tumor cells infiltrating the skin expressed 3Al antigen in 44% and cellular activation antigens Ia and/or Tac in 78% of patients with MF/SS. No consistent phenotypic differences were found between ATL cells from ATLV (HTLV) antibody-positive patients and tumor cells of patients with MF/SS who lacked this antibody. In contrast, a group of nonepidermotropic T-cell lymphomas showed phenotypic differences from MF/SS and ATL in all but 1 case. These cases were distinguished by the frequent absence of T3, T4, and Leu 1 antigens in 3 large-cell lymphomas; frequent expression of Ki-1 antigen, a Hodgkin's disease-associated antigen, in 2 cases with RS-like cells; and an immature thymocyte phenotype in lymphoblastic lymphoma. These findings demonstrate that tumor-cell phenotypes can be useful in distinguishing different histologic types of cutaneous T-cell lymphoma.
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Antígenos de Neoplasias/análise , Antígenos de Histocompatibilidade Classe II/análise , Leucemia/imunologia , Linfoma/imunologia , Micose Fungoide/imunologia , Síndrome de Sézary/imunologia , Adulto , Idoso , Feminino , Humanos , Técnicas Imunoenzimáticas , Linfoma/ultraestrutura , Masculino , Pessoa de Meia-Idade , Micose Fungoide/ultraestrutura , Linfócitos TRESUMO
A cDNA of the C beta 2 gene of the T-cell receptor was used as a probe to investigate the clonal composition of T cells in skin lesions of 5 patients with lymphomatoid papulosis (LyP), a chronic recurrent eruption characterized by morphologically abnormal activated T cells in the cutaneous infiltrate. Clonal T-cell populations, as evidenced by rearranged DNA bands, were demonstrated in the skin lesions of four patients, one of whom has shown clinical progression toward lymphoma. Three of these patients had lesions of type A histology, a type previously shown to be associated with aneuploidy. The remaining patient with clonal lesions appeared to have the same gene rearrangement pattern in DNA obtained from separate lesions taken 11 months apart, providing evidence that the T cells in both sites were derived from the same clone. This patient had lesions of type B histology, which is not associated with aneuploidy. Absence of a rearranged band and deletion or near absence of the 10.8 kb band in Eco RI digests was interpreted as evidence of polyclonal T-cell hyperplasia, accounting for the skin infiltrate of a fifth patient who had a prolonged clinical course without progression to lymphoma. This patient had lesions of type A histology with frequent Ki-1-positive Reed-Sternberg-like cells. Our results show that gene rearrangement analysis provides information that is independent of histology in LyP and may in part explain the variable progression of LyP to lymphoma in 10-20% of patients.
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Dermatopatias Vesiculobolhosas/patologia , Linfócitos T/classificação , Células Clonais/patologia , DNA/genética , Humanos , Fenótipo , Dermatopatias Vesiculobolhosas/genética , Dermatopatias Vesiculobolhosas/imunologia , Linfócitos T/imunologia , Linfócitos T/patologia , Linfócitos T/fisiologiaRESUMO
A distinctive immunologic phenotype was demonstrated for the characteristic large atypical cells in skin lesions of 9 patients with lymphomatoid papulosis (LP). Coexpression of Hodgkin's disease (HD)-associated antigen(s) Ki-1, and often Leu-M1, with helper T-cell antigens T11, T4, and T3 and cellular activation antigens Tac, Ia, and T9 was the most common phenotype, observed in 6 of 9 cases. In 2 cases T-cell-specific antigens were not detected, and the phenotype was indistinguishable from Reed-Sternberg (RS) cells of HD. Numerous Ki-1 positive cells and infrequent expression of Leu-1 antigen by large atypical cells in LP cases facilitated the differential diagnosis between LP and mycosis fungoides. A possible transition between small, medium, and large cells expressing only T-cell antigens and large transformed RS-like cells expressing both T-cell and HD-associated antigens was shown by immunoelectron microscopy. These immunologic findings should prove useful for the diagnosis of LP and may help to explain the unexpectedly frequent clinical associations of LP, mycosis fungoides, and HD.
Assuntos
Dermatopatias/imunologia , Antígenos de Neoplasias/imunologia , Doença de Hodgkin/imunologia , Humanos , Técnicas Imunoenzimáticas , Ativação Linfocitária , Microscopia Eletrônica , Micose Fungoide/patologia , Dermatopatias/patologia , Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologiaRESUMO
P-selectin glycoprotein ligand 1 (PSGL-1) is a mucin-like glycoprotein expressed on the surface of myeloid cells and serves as the high affinity counterreceptor for P-selectin. The PSGL-1-P-selectin interaction is calcium dependent and requires presentation of sialyl-Lewisx (sLex)-type structures on the O-linked glycans of PSGL-1. We report here the identification of a non-carbohydrate component of the binding determinant that is critical for high affinity binding to P-selectin. Located within the first 19 amino acids, this anionic polypeptide segment contains at least one sulfated tyrosine residue. We propose that this sulfotyrosine-containing segment of PSGL-1, in conjunction with sLex presented on O-linked glycans, constitutes the high affinity P-selectin-binding site.
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Glicoproteínas de Membrana/metabolismo , Selectina-P/metabolismo , Peptídeos/química , Tirosina/análogos & derivados , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Análise Mutacional de DNA , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/genética , Modelos Moleculares , Dados de Sequência Molecular , Neuraminidase/metabolismo , Ligação Proteica , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Deleção de Sequência , Relação Estrutura-Atividade , Tirosina/análiseRESUMO
We describe a large-cell lymphoma of activated lymphoid cells in six children and adolescents. The presenting clinical features of regressing skin lesions and peripheral lymphadenopathy, sinus infiltration of lymph nodes, and infrequent tumor cell erythrophagocytosis resulted in initial diagnoses of malignant or regressing atypical histiocytosis in five cases. Binucleate and multinucleate tumor cells, sometimes with prominent eosinophilic nucleoli, resembled Reed-Sternberg (RS) cells and occasionally were found in a cytoarchitectural milieu that was consistent with a diagnosis of Hodgkin's disease (HD). The tumor cells did in fact express the HD-associated antigen Ki-1, but unlike most types of HD, the RS-like cells expressed common leukocyte antigen and were negative for Leu-M1. A T cell origin for the malignant cells was demonstrated with monoclonal antibodies in two cases, by focal staining for nonspecific esterase in one case, and by rearrangement of the beta-chain genes for the T cell receptor in a fourth case. These studies provide further evidence that some cases previously interpreted as malignant or regressing atypical histiocytosis and some types of HD are actually T cell disorders.
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Linfoma/patologia , Adolescente , Antígenos de Neoplasias/análise , Antígenos de Superfície/análise , Diferenciação Celular , Criança , Feminino , Histocitoquímica , Doença de Hodgkin/imunologia , Humanos , Linfonodos/patologia , Masculino , Receptores de Antígenos de Linfócitos T/genética , Formação de Roseta , Pele/patologia , Linfócitos T/patologiaRESUMO
P-selectin glycoprotein ligand-1 (PSGL-1) is the high affinity counter-receptor for P-selectin on myeloid cells (Sako, D., Chang, X.J., Barone, K.M., Vachino, G., White, H.M., Shaw, G., Veldman, G.M., Bean, K.M., Ahern, T.J., Furie, B., Cumming, D. A., and Larsen, G. R. (1993) Cell 75, 1179-1186). Here we demonstrate that PSGL-1 is also widely distributed on T- and B-lymphocytic tumor cell lines, resting peripheral blood T and B cells, and on stimulated peripheral blood T cell and intestinal intraepithelial lymphocyte (IEL) lines. However, the majority of PSGL-1-positive resting peripheral blood lymphocytic cells and lymphoid tumor cell lines do not display significant P-selectin binding. In contrast, in vitro stimulated peripheral blood T cell and IEL lines avidly bind P-selectin, and PSGL-1 is the sole high affinity counter-receptor mediating this binding. During the course of in vitro stimulation, cell surface expression levels of PSGL-1 do not change as P-selectin binding increases. Rather, the activities of two glycosyltransferases reportedly involved in the production of functional PSGL-1 in myeloid cells are substantially higher in the stimulated T-lymphocytic lines than in resting T lymphocytes, consistent with the hypothesis that activation-dependent post-translational events contribute to the expression of functional PSGL-1 on lymphocytes.
Assuntos
Moléculas de Adesão Celular/metabolismo , Ativação Linfocitária , Linfócitos/imunologia , Glicoproteínas de Membrana/metabolismo , Glicoproteínas da Membrana de Plaquetas/metabolismo , Receptores de Superfície Celular/metabolismo , Linfócitos T/imunologia , Sequência de Aminoácidos , Animais , Linfócitos B/imunologia , Células CHO , Linhagem Celular , Cricetinae , Citometria de Fluxo , Expressão Gênica , Humanos , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/biossíntese , Dados de Sequência Molecular , Selectina-P , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Receptores de Superfície Celular/imunologia , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Transfecção , Células Tumorais CultivadasRESUMO
The initial adhesive interactions between circulating leukocytes and endothelia are mediated, in part, by P-selectin. We now report the expression cloning of a functional ligand for P-selectin from an HL-60 cDNA library. The predicted amino acid sequence reveals a novel mucin-like transmembrane protein. Significant binding of transfected COS cells to P-selectin requires coexpression of both the protein ligand and a fucosyltransferase. This binding is calcium dependent and can be inhibited by a neutralizing monoclonal antibody to P-selectin. Cotransfected COS cells express the ligand as a homodimer of 220 kd. A soluble ligand construct, when coexpressed with fucosyltransferase in COS cells, also mediates P-selectin binding and is immunocrossreactive with the major HL-60 glycoprotein that specifically binds P-selectin.
Assuntos
Glicoproteínas de Membrana/biossíntese , Glicoproteínas da Membrana de Plaquetas/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Southern Blotting , Células CHO , Adesão Celular , Moléculas de Adesão Celular/metabolismo , Linhagem Celular , Clonagem Molecular , Cricetinae , DNA Complementar/metabolismo , Endotélio Vascular/fisiologia , Biblioteca Gênica , Humanos , Leucemia Promielocítica Aguda , Leucócitos/fisiologia , Substâncias Macromoleculares , Glicoproteínas de Membrana/metabolismo , Dados de Sequência Molecular , Selectina-P , Homologia de Sequência de Aminoácidos , Transfecção , Células Tumorais CultivadasRESUMO
P-selectin on platelets and endothelial cells and E-selectin on endothelial cells are leukocyte receptors that recognize lineage-specific carbohydrates on neutrophils and monocytes. The proposed ligands for these receptors contain the Le(x) core and sialic acid. Since other investigators have shown that both E-selectin and P-selectin bind to sialylated Le(x), we evaluated whether E-selectin and P-selectin recognize the same counter-receptor on leukocytes. The interaction of HL60 cells with Chinese hamster ovary (CHO) cells expressing P-selectin or E-selectin was studied. To determine whether a protein component is required in addition to sialyl Le(x) for either P-selectin or E-selectin recognition, HL60 cells or neutrophils were digested with proteases, including chymotrypsin, elastase, proteinase Glu-C, ficin, papain, or thermolysin. Cells treated with these proteases bound E-selectin but not P-selectin. Fucosidase or neuraminidase treatment of HL60 cells markedly decreased binding to both E-selectin- and P-selectin-expressing CHO cells. Growth of HL60 cells in tunicamycin inhibited the ability of these cells to support P-selectin-mediated binding and, to a lesser extent, E-selectin-mediated binding. Purified P-selectin inhibited CHO:P-selectin binding to HL60 cells, but incompletely inhibited CHO:E-selectin binding to HL60 cells. However, purified soluble E-selectin inhibited CHO:P-selectin and CHO:E-selectin binding to HL60 cells equivalently and completely. COS cells, unable to bind to E-selectin or P-selectin, bound E-selectin but not P-selectin upon transfection with alpha-1,3-fucosyltransferase or alpha-1,3/1,4-fucosyltransferase. Similarly, LEC 11 cells expressing sialyl Le(x) bound E-selectin- but not P-selectin-expressing CHO cells. Sambucus nigra lectin, specific for the sialyl-2,6 beta Gal/GalNAc linkage, inhibited P-selectin but not E-selectin binding to HL60 cells. Although sialic acid and Le(x) are components of the P-selectin ligand and the E-selectin ligand, these results indicate that the ligands are related, having overlapping specificities, but are structurally distinct. A protein component containing sialyl Le(x) in proximity to sialyl-2,6 beta Gal structures on the P-selectin ligand may contribute to its specificity for P-selectin.
Assuntos
Moléculas de Adesão Celular/metabolismo , Adesão Celular , Leucócitos/metabolismo , Glicoproteínas da Membrana de Plaquetas/metabolismo , Animais , Sequência de Bases , Células CHO , Sequência de Carboidratos , Moléculas de Adesão Celular/genética , Linhagem Celular , Cricetinae , DNA/genética , Selectina E , Humanos , Antígenos CD15/metabolismo , Ligantes , Dados de Sequência Molecular , Selectina-P , Glicoproteínas da Membrana de Plaquetas/genética , Ácidos Siálicos/metabolismo , Especificidade por Substrato , Transfecção , Tunicamicina/farmacologiaRESUMO
Carbohydrate recognition by the human endothelial-leukocyte adhesion molecule, E-selectin, has been investigated by binding studies using 3H-labeled Chinese hamster ovary cells expressing different levels of the transfected full-length adhesion molecule and a series of structurally defined oligosaccharides linked to the lipid phosphatidylethanolamine dipalmitoate (neoglycolipids) and synthetic glycolipids chromatographed on silica gel plates or immobilized on plastic wells. Evidence is presented for density-dependent binding of the membrane-associated E-selectin not only to 3'-sialyl-lacto-N-fucopentaose II (3'-S-LNFP-II) and 3'-sialyl-lacto-N-fucopentaose III (3'-S-LNFP-III) which express the sialyl Le(a) and sialyl Le(x) antigens, respectively, but also to the nonsialylated analogue LNFP-II; there is a threshold density of E-selectin required for binding to these sialylated sequences, and binding to the nonsialylated analogue is a property only of cells with the highest density of E-selectin expression. The presence of fucose linked to subterminal rather than to an internal N-acetylglucosamine is shown to be a requirement for E-selectin binding, and although the presence of sialic acid 3-linked to the terminal galactose of the LNFP-II or LNFP-III sequences substantially enhances E-selectin binding, the presence of 6-linked sialic acid abolishes binding. E-selectin binding is unaffected in the presence of the blood group H fucose (alpha 1-2 linked to galactose to form the Le(b) antigen). However, the binding is abolished when in addition alpha 1-3-linked N-acetylgalactosamine to the galactose (blood group A antigen) is present. These results indicate that some E-selectin-mediated adhesive events may be influenced by blood group status.