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1.
Appl Environ Microbiol ; 86(20)2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32769182

RESUMO

We sought to identify and study the antibiofilm protein secreted by the marine bacterium Pseudoalteromonas sp. strain 3J6. The latter is active against marine and terrestrial bacteria, including Pseudomonas aeruginosa clinical strains forming different biofilm types. Several amino acid sequences were obtained from the partially purified antibiofilm protein, named alterocin. The Pseudoalteromonas sp. 3J6 genome was sequenced, and a candidate alt gene was identified by comparing the genome-encoded proteins to the sequences from purified alterocin. Expressing the alt gene in another nonactive Pseudoalteromonas sp. strain, 3J3, demonstrated that it is responsible for the antibiofilm activity. Alterocin is a 139-residue protein that includes a predicted 20-residue signal sequence, which would be cleaved off upon export by the general secretion system. No sequence homology was found between alterocin and proteins of known functions. The alt gene is not part of an operon and adjacent genes do not seem related to alterocin production, immunity, or regulation, suggesting that these functions are not fulfilled by devoted proteins. During growth in liquid medium, the alt mRNA level peaked during the stationary phase. A single promoter was experimentally identified, and several inverted repeats could be binding sites for regulators. alt genes were found in about 30% of the Pseudoalteromonas genomes and in only a few instances of other marine bacteria of the Hahella and Paraglaciecola genera. Comparative genomics yielded the hypothesis that alt gene losses occurred within the Pseudoalteromonas genus. Overall, alterocin is a novel kind of antibiofilm protein of ecological and biotechnological interest.IMPORTANCE Biofilms are microbial communities that develop on solid surfaces or interfaces and are detrimental in a number of fields, including for example food industry, aquaculture, and medicine. In the latter, antibiotics are insufficient to clear biofilm infections, leading to chronic infections such as in the case of infection by Pseudomonas aeruginosa of the lungs of cystic fibrosis patients. Antibiofilm molecules are thus urgently needed to be used in conjunction with conventional antibiotics, as well as in other fields of application, especially if they are environmentally friendly molecules. Here, we describe alterocin, a novel antibiofilm protein secreted by a marine bacterium belonging to the Pseudoalteromonas genus, and its gene. Alterocin homologs were found in about 30% of Pseudoalteromonas strains, indicating that this new family of antibiofilm proteins likely plays an important albeit nonessential function in the biology of these bacteria. This study opens up the possibility of a variety of applications.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes/efeitos dos fármacos , Pseudoalteromonas/genética , Proteínas de Bactérias/biossíntese
2.
Glycobiology ; 26(9): 973-983, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27026155

RESUMO

Mannuronan C5-epimerases (ManC5-Es) catalyze in brown algae the remodeling of alginate, a major cell-wall component which is involved in many biological functions in these organisms. ManC5-Es are present as large multigenic families in brown algae, likely indicating functional specificities and specializations. ManC5-Es control the distribution pattern of (1-4) linked ß-d-mannuronic acid (M) and α-l-guluronic acid (G) residues in alginates, giving rise to widely different polysaccharide compositions and sequences, depending on tissue, season, age, or algal species. As such they are also a source of powerful new tools for the biotechnological and enzymatic processing of alginates, to match the growing interest for food hydrocolloids and in biomedical and nanotechnological applications. We report here the first heterologous production of a ManC5-E of brown algal origin that is successfully refolded in an active form. The activity was measured by 1H NMR and by an indirect enzymatic assay using a known bacterial alginate lyase. The transcript expression as a function of the developmental program of the brown alga Ectocarpus, together with the bioinformatic analyses of the corresponding gene context of this multigenic family, is also presented.


Assuntos
Carboidratos Epimerases/química , Parede Celular/enzimologia , Phaeophyceae/enzimologia , Polissacarídeos/biossíntese , Alginatos/metabolismo , Sequência de Aminoácidos , Carboidratos Epimerases/genética , Carboidratos Epimerases/metabolismo , Parede Celular/química , Parede Celular/genética , Ácido Glucurônico/metabolismo , Ácidos Hexurônicos/química , Ácidos Hexurônicos/metabolismo , Espectroscopia de Ressonância Magnética , Phaeophyceae/genética , Polissacarídeos/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética
3.
Proteomics ; 15(23-24): 3954-68, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26154304

RESUMO

Extreme reduction in cellular water content leads to desiccation, which, if persistent, affects the physiology of organisms, mainly through oxidative stress. Some organisms are highly tolerant to desiccation, including resurrection plants and certain intertidal seaweeds. One such species is Pyropia orbicularis, a rhodophycean that colonizes upper intertidal zones along the Chilean coast. Despite long, daily periods of air exposure due to tides, this alga is highly tolerant to desiccation. The present study examined the proteome of P. orbicularis by 2DE and LC-MS/MS analyses to determine the proteins associated with desiccation tolerance (DT). The results showed that, under natural conditions, there were significant changes in the protein profile during low tide as compared to naturally hydrated plants at high tide. These changes were mainly in newly appeared proteins spots such as chaperones, monodehydroascorbate reductase, and manganese superoxide dismutase, among others. Previously undescribed proteins under desiccation conditions included phycobiliproteins, glyoxalase I, and phosphomannomutase. These changes evidenced that several physiological responses involved in DT are activated during low tide, including decreased photosynthetic activity, increased antioxidant capacity, and the preservation of cell physiology by regulating water content, cell wall structure, and cell volume. Similar responses have been observed in resurrection plants and bryophytes exposed to desiccation. Therefore, the coordinated activation of different desiccation tolerance pathways in P. orbicularis could explain the successful biological performance of this seaweed in the upper intertidal rocky zones.


Assuntos
Alga Marinha/metabolismo , Adaptação Fisiológica , Dessecação , Estresse Oxidativo/fisiologia , Proteínas de Plantas/metabolismo , Rodófitas/metabolismo , Rodófitas/fisiologia , Alga Marinha/fisiologia , Estresse Fisiológico/fisiologia
5.
Molecules ; 19(10): 15374-90, 2014 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-25264828

RESUMO

The induction of plant immunity by Pathogen Associated Molecular Patterns (PAMPs) constitutes a powerful strategy for crop protection. PAMPs indeed induce general defense responses in plants and thus increase plant resistance to pathogens. Phytophthora infestans culture filtrates (CCFs) are known to induce defense responses and decrease the severity of soft rot due to Pectobacterium atrosepticum in potato tubers. The aim of this study was to identify and characterize the active compounds from P. infestans filtrate. The filtrate was fractionated by gel filtration, and the protection effects against P. atrosepticum and the ability to induce PAL activity were tested for each fraction. The fraction active in protection (F1) also induced PAL activity, as did the whole filtrate. Three elicitins (INF1, INF4 and INF5) were identified in F1b, subfraction of F1, by MALDI-TOF-MS and MS/MS analyses. However, deproteinized F1b still showed biological activity against the bacterium, revealing the presence of an additional active compound. GC-MS analyses of the deproteinized fraction highlighted the presence of a galactan-based complex polysaccharide. These experiments demonstrate that the biological activity of the CCF against P. atrosepticum results from a combined action of three elicitins and a complex polysaccharide, probably through the activation of general defense responses.


Assuntos
Antibacterianos/farmacologia , Pectobacterium/efeitos dos fármacos , Phytophthora infestans/metabolismo , Polissacarídeos/farmacologia , Proteínas/farmacologia , Sequência de Aminoácidos , Antibacterianos/química , Fracionamento Químico , Ativação Enzimática/efeitos dos fármacos , Dados de Sequência Molecular , Fenilalanina Amônia-Liase/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Proteínas/química , Alinhamento de Sequência , Solanum tuberosum/efeitos dos fármacos , Solanum tuberosum/enzimologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em Tandem
6.
J Immunol ; 185(3): 1550-7, 2010 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-20601596

RESUMO

During the antiphospholipid syndrome, beta2-gpI interacts with phospholipids on endothelial cell (EC) surface to allow the binding of autoantibodies. However, induced-pathogenic intracellular signals suggest that beta2-gpI associates also with a receptor that is still not clearly identified. TLR2 and TLR4 have long been suspected, yet interactions between TLRs and beta2-gpI have never been unequivocally proven. The aim of the study was to identify the TLR directly involved in the binding of beta2-gpI on EC surface. beta2-gpI was not synthesized and secreted by ECs in vitro, but rather taken up from FCS. This uptake occurred through association with TLR2 and TLR4 which partitioned together in the lipid rafts of ECs. After coimmunoprecipitation, mass-spectrometry identification of peptides demonstrated that TLR2, but not TLR4, was implicated in the beta2-gpI retention. These results were further confirmed by plasmon resonance-based studies. Finally, siRNA were used to obtain TLR2-deficient ECs that lost their ability to bind biotinylated beta2-gpI and to trigger downstream phosphorylation of kinases and activation of NFkappaB. TLR4 may upregulate TLR2 expression, thereby contributing to beta2-gpI uptake. However, our data demonstrate that direct binding of beta2-gpI on EC surface occurs through direct interaction with TLR2. Furthermore, signaling for anti-beta2-gpI may be envisioned as a multiprotein complex concentrated in lipid rafts on the EC membrane.


Assuntos
Endotélio Vascular/metabolismo , Receptor 2 Toll-Like/metabolismo , beta 2-Glicoproteína I/metabolismo , Sequência de Aminoácidos , Animais , Bovinos , Linhagem Celular , Células Hep G2 , Humanos , Imunoprecipitação , Microdomínios da Membrana/imunologia , Microdomínios da Membrana/metabolismo , Dados de Sequência Molecular , Peptídeos/isolamento & purificação , Peptídeos/metabolismo , Ligação Proteica/imunologia , Receptor 2 Toll-Like/biossíntese , Receptor 2 Toll-Like/isolamento & purificação , Receptor 4 Toll-Like/biossíntese , Receptor 4 Toll-Like/isolamento & purificação , Receptor 4 Toll-Like/metabolismo , Células U937 , beta 2-Glicoproteína I/biossíntese
7.
Bioorg Chem ; 44: 25-34, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22884431

RESUMO

The sequence of bromoperoxidase II from the brown alga Ascophyllum nodosum was determined from a full length cloned cDNA, obtained from a tandem mass spectrometry RT-PCR-approach. The clone encodes a protein composed of 641 amino-acids, which provides a mature 67.4 kDa-bromoperoxidase II-protein (620 amino-acids). Based on 43% sequence homology with the previously characterized bromoperoxidase I from A. nodosum, a tertiary structure was modeled for the bromoperoxidase II. The structural model was refined on the basis of results from gel filtration and vanadate-binding studies, showing that the bromoperoxidase II is a hexameric metalloprotein, which binds 0.5 equivalents of vanadate as cofactor per 67.4 kDa-subunit, for catalyzing oxidation of bromide by hydrogen peroxide in a bi-bi-ping-pong mechanism (k(cat) = 153 s(-1), 22 °C, pH 5.9). Bromide thereby is converted into a bromoelectrophile of reactivity similar to molecular bromine, based on competition kinetic data on phenol bromination and correlation analysis. Reactivity provided by the bromoperoxidase II mimics biosynthesis of methyl 4-bromopyrrole-2-carboxylate, a natural product isolated from the marine sponge Axinella tenuidigitata.


Assuntos
Ascophyllum/enzimologia , Brometos/metabolismo , Peroxidases/química , Peroxidases/metabolismo , Sequência de Aminoácidos , Ascophyllum/química , Ascophyllum/genética , Clonagem Molecular , Halogenação , Modelos Moleculares , Dados de Sequência Molecular , Oxirredução , Peroxidases/genética , Conformação Proteica , Alinhamento de Sequência , Vanadatos/metabolismo
8.
Mar Pollut Bull ; 175: 113131, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34839953

RESUMO

This study examined the physiological responses of the larval stages of Haliotis tuberculata, an economically important abalone, to combined temperature (17 °C and 19 °C) and pH (ambient pH and -0.3 units, i.e., +200% increase in seawater acidity) in a full factorial experiment. Tissue organogenesis, shell formation, and shell length significantly declined due to low pH. High temperature significantly increased the proportion of fully shelled larvae at 24 h post-fertilization (hpf), but increased the proportion of unshelled larvae at 72 hpf. Percentage of swimming larvae at 24 hpf, 72 hpf and 96 hpf significantly declined due to high temperature, but not because of low pH. Larval settlement increased under high temperature, but was not affected by low pH. Despite the fact that no interaction between temperature and pH was observed, the results provide additional evidence on the sensitivity of abalone larvae to both low pH and high temperature. This may have negative consequences for the persistence of abalone populations in natural and aquaculture environments in the near future.


Assuntos
Gastrópodes , Aquecimento Global , Animais , Gastrópodes/fisiologia , Concentração de Íons de Hidrogênio , Larva , Oceanos e Mares , Água do Mar , Temperatura
9.
Mar Environ Res ; 181: 105753, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36130468

RESUMO

CO2 absorption is leading to ocean acidification (OA), which is a matter of major concern for marine calcifying species. This study investigated the effects of simulated OA on the reproduction of European abalone Haliotis tuberculata and the survival of its offspring. Four-year-old abalone were exposed during reproductive season to two relevant OA scenarios, ambient pH (8.0) and low pH (7.7). After five months of exposure, abalone were induced to spawn. The gametes, larvae and juveniles were then exposed for five months to the same pH conditions as their parents. Several biological parameters involved in adult reproduction as well as in larval, post-larval and juvenile fitness were measured. No effects on gametes, fertilisation or larval oxidative stress response were detected. However, developmental abnormalities and significant decreases in shell length and calcification were observed at veliger stages. The expression profile of a GABA A receptor-like gene appeared to be regulated by pH, depending on larval stage. Larval and post-larval survival was not affected by low pH. However, a lower survival and a reduction of growth were recorded in juveniles at pH 7.7. Our results confirm that OA negatively impacts larval and juvenile fitness and suggest the absence of carry-over effects on abalone offspring. This may compromise the survival of abalone populations in the near future.


Assuntos
Gastrópodes , Água do Mar , Animais , Concentração de Íons de Hidrogênio , Acidificação dos Oceanos , Gastrópodes/fisiologia , Larva/fisiologia
10.
Proteomics ; 10(11): 2074-88, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20373519

RESUMO

Ectocarpus siliculosus is a cosmopolitan brown alga with capacity to thrive in copper enriched environments. Analysis of copper toxicity was conducted in two strains of E. siliculosus isolated from (i) an uncontaminated coast in southern Peru (Es32) and (ii) a copper polluted rocky beach in northern Chile (Es524). Es32 was more sensitive than Es524, with toxicity detected at 50 microg/L Cu, whereas Es524 displayed negative effects only when exposed to 250 microg/L Cu. Differential soluble proteome profiling for each strain exposed to sub-lethal copper levels allowed to identify the induction of proteins related to processes such as energy production, glutathione metabolism as well as accumulation of HSPs. In addition, the inter-strain comparison of stress-related proteomes led to identify features related to copper tolerance in Es524, such as striking expression of a PSII Mn-stabilizing protein and a Fucoxanthine chlorophyll a-c binding protein. Es524 also expressed specific stress-related enzymes such as RNA helicases from the DEAD box families and a vanadium-dependent bromoperoxidase. These observations were supported by RT-qPCR for some of the identified genes and an enzyme activity assay for vanadium-dependent bromoperoxidase. Therefore, the occurrence of two different phenotypes within two distinct E. siliculosus strains studied at the physiological and proteomic levels strongly suggest that persistent copper stress may represent a selective force leading to the development of strains genetically adapted to copper contaminated sites.


Assuntos
Cobre/toxicidade , Phaeophyceae/efeitos dos fármacos , Phaeophyceae/metabolismo , Proteômica/métodos , Adaptação Fisiológica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos
11.
Ann Pathol ; 28(1): 2-8, 2008 Feb.
Artigo em Francês | MEDLINE | ID: mdl-18538708

RESUMO

In order to illustrate the clinical and histological presentations of laryngeal atypical carcinoids and their potential course, we report six cases. We evaluated the factors predictive of local recurrence and metastatic diffusion. For each case, we noted the mitotic index, the quality of the resection, the limits of the tumor and the presence of necrosis. An immunohistochemical study was carried out with a series of antibodies (cytokeratins; D(2)40; CD31; MIB1; P53; P16; TTF1...). The clinical presentation we observed was quite similar to that reported in the literature. These tumors are CK7+, CK8+, CK19+, CK5-6-, CK14- and CK20-. P16 is constantly positive. Only the mitotic index and the lymphatic presence of embolus were correlated with the time course. The tumor is more aggressive when the mitotic index is high and an unfavorable course is observed when there are lymphatic emboli or when the Ki67 index is higher than 5%.


Assuntos
Cartilagem Aritenoide/patologia , Tumor Carcinoide/cirurgia , Neoplasias Laríngeas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/patologia , Feminino , Humanos , Neoplasias Laríngeas/patologia , Laringectomia , Masculino , Pessoa de Meia-Idade , Mitose
12.
N Engl J Med ; 350(13): 1287-95, 2004 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-15044639

RESUMO

BACKGROUND: The efficacy of first-line intensive chemotherapy plus transplantation of autologous hematopoietic stem cells in adults with disseminated aggressive lymphoma is unknown. METHODS: We compared high-dose therapy plus autologous stem-cell support with the standard regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in a randomized trial. The patients were 15 to 60 years of age, had untreated aggressive lymphoma, and were at low, low intermediate, or high intermediate risk of death (i.e., a maximum of two adverse prognostic factors) according to the age-adjusted International Prognostic Index. The primary outcome was event-free survival at five years. RESULTS: Of 207 consecutive patients, 197 underwent randomization; 99 were assigned to receive CHOP, and 98 to receive high-dose chemotherapy plus stem-cell transplantation. Overall, 78 percent of the patients completed the assigned treatment; the median follow-up was four years. The estimated event-free survival rate (+/-SD) at five years was significantly higher among patients who received high-dose therapy than among patients who received CHOP (55+/-5 percent vs. 37+/-5 percent, P=0.037). Among patients with a high intermediate risk of death, according to the age-adjusted International Prognostic Index, the five-year survival rate was significantly higher after high-dose therapy than after CHOP (74+/-6 percent vs. 44+/-7 percent, P=0.001). CONCLUSIONS: High-dose chemotherapy with autologous stem-cell support is superior to CHOP in adults with disseminated aggressive lymphoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma/terapia , Transplante de Células-Tronco , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Humanos , Linfoma/tratamento farmacológico , Linfoma/mortalidade , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Indução de Remissão , Análise de Sobrevida , Transplante Autólogo , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Vindesina/administração & dosagem , Vindesina/efeitos adversos
13.
Haematologica ; 92(10): 1335-42, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18024371

RESUMO

BACKGROUND AND OBJECTIVES: Diffuse large B-cell lymphomas (DLBCL) are common lymphomas that have been classified into three subgroups on the basis of their patterns of gene expression. The aim of this study was to characterize the clinical, biological, immunophenotypic and cytogenetic features of DLBCL with concurrent t(14;18) and 8q24/c-MYC rearrangement. DESIGN AND METHODS: Sixteen cases of DLBCL with the dual translocation were identified between 1998 and January 2006. The clinical features of these cases were examined and morphological, immunohistochemical, flow cytometric and cytogenetic analyses were performed. RESULTS: All patients had aggressive features: B symptoms (81%), ECOG performance status >2 (81%), elevated lactate dehydrogenase (100%), stage IV disease (100%) with at least one extra-nodal localization (bone marrow, blood and central nervous system involvement in 93%, 50% and 50%, respectively) and age-adjusted IPI score of 3 in 81%. Despite intensive chemotherapy regimens (including allogeneic transplants), all patients died of disease progression. Progression-free and overall survival was 4 and 5 months, respectively. Immunophenotyping analysis (CD20, CD10, Bcl-6, Mum-1, Bcl-2 CD138, MIB1, CD19, CD5, CD38 and sIg) was performed and showed DLBCL with a germinal center (GC) profile. Ki-67 staining ranged from 70 to 90%. All cases assessed by cytogenetics analysis [conventional cytogenetic and/or fluorescence in situ hybridization (FISH)] had a complex karyotype. In one case, we identified a 8q24/c-MYC translocation variant never reported in DLBCL before: t(8;9)(q24;p13) and t(14;18)(q32;q21). The BCL-6 rearrangement was investigated by FISH and found to rearranged in four cases. INTERPRETATION AND CONCLUSIONS: In conclusion, DLBCL with concurrent t(14;18) and 8q24/c-MYC rearrangement is a subgroup of GC-DLBCLwith poor outcome. It is worth searching for the coexistence of dual translocations in Bcl-2-positive DLBCL with unusual aggressive presentation.


Assuntos
Cromossomos Humanos Par 8/genética , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Adulto , Idoso , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Prognóstico
14.
Am J Surg Pathol ; 30(2): 223-9, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16434897

RESUMO

Anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL) are recognized as biologically distinct entities. However, occasionally, these two entities may share some morphologic features responsible for diagnostic difficulties. In the last 10 years, we have collected 380 cases of ALK-positive ALCL of which 10 cases were originally diagnosed as nodular sclerosis classic HL (NSHL) on conventional histopathological examination. After immunostaining, these cases proved to be ALK-positive ALCL mimicking HL (so-called Hodgkin-like ALCL). These cases account for 2.6% of our cases of ALK-positive ALCL (10 of 380 cases). Median age was 11 years (3-92 years) with a female predominance (male/female ratio, 3:7). Characteristically, these lesions showed thick nodular fibrosing bands highly suggestive of NSHL. Neoplastic cells were scarce in 6 cases, whereas in the 4 remaining cases, sheets of tumor cells were also present. A perivascular and a sinusoidal growth pattern was observed in various degrees in all cases. Few binucleated Reed-Sternberg-like cells were present in every case in a background of small lymphocytes. Inflammatory cells (ie, granulocytes, eosinophils, and histiocytes) were rare. Neoplastic cells were positive for CD30 (10 of 10 cases), ALK protein (10 of 10 cases), epithelial membrane antigen (EMA) (9 of 9 cases), CD43 (6 of 9 cases), and perforin (8 of 8 cases), but negative for CD15 (10 of 10 cases), CD20 (10 of 10 cases), Pax5/BSAP (6 of 6 cases), and EBV (8 of 8 cases). In addition, in 7 cases, neoplastic cells were of T-phenotype, whereas the 3 remaining cases were considered to be of null/undetermined phenotype. Although rare, Hodgkin-like ALCL may mimic NSHL, and it is advisable to include EMA in the first line panel and to ask for ALK staining in EMA-positive, CD15-negative lesions with morphologic features suggestive of NSHL.


Assuntos
Biomarcadores Tumorais/análise , Doença de Hodgkin/patologia , Linfoma Difuso de Grandes Células B/patologia , Proteínas Tirosina Quinases/metabolismo , Adolescente , Adulto , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Criança , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Receptores Proteína Tirosina Quinases , Esclerose/patologia
15.
Haematologica ; 90(11): 1580-2, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16266909

RESUMO

We retrospectively investigated the outcome of 30 newly diagnosed patients with mantle cell lymphoma treated with high-dose therapy and autologous stem cell transplantation in first response. With a median follow-up of 55 months, the 5-year overall-survival is 62%, the 5-year progression-free-survival is 40% and no secondary malignancy has occurred.


Assuntos
Linfoma de Célula do Manto/cirurgia , Transplante de Células-Tronco/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Retrospectivos , Análise de Sobrevida , Transplante Autólogo , Vincristina/administração & dosagem
16.
J Photochem Photobiol B ; 143: 52-60, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25600264

RESUMO

In temperate saltmarshes, halophytic plants have to daily protect their internal tissues against sunlight and UV rays. Consequently, they develop adaptive responses such as the synthesis of secondary metabolites, including polyphenols. The present study focused on the biological activities of fractions enriched in polyphenols from Salicornia ramosissima. Three different extracts were obtained by purification processes to concentrate polyphenols: a crude hydroalcoholic extract, and two purified fractions: an ethyl acetate fraction (EAF) and an aqueous fraction. Phenolic and flavonoid contents, antioxidant (DPPH radical-scavenging activity, reducing activity, ß-carotene linoleic acid system and the ORAC method) and sunscreen properties (Sun Protection Factor and UVA-Protection Factor) were assessed by in vitro tests. The purification process was effective in increasing phenolic and flavonoid contents as well as antioxidant and sunscreen capacities of the EAF. The EAF appeared to be a broad spectrum UV absorber. The chemical structure of 10 EAF polyphenols was elucidated using 2D NMR and mass spectrometry spectra. Furthermore, a correlation was observed between phenolic composition and biological activity. These findings are encouraging for the future use of S. ramosissima as a potential source of antioxidant and photoprotectant molecules for industrial applications.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Chenopodiaceae/química , Polifenóis/química , Polifenóis/farmacologia , Protetores contra Radiação/química , Protetores contra Radiação/farmacologia , Acetatos/química , Antioxidantes/isolamento & purificação , Polifenóis/isolamento & purificação , Protetores contra Radiação/isolamento & purificação
17.
Sci Transl Med ; 7(317): 317ra196, 2015 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-26659570

RESUMO

In acute and chronic inflammation, neutrophils and platelets, both of which promote monocyte recruitment, are often activated simultaneously. We investigated how secretory products of neutrophils and platelets synergize to enhance the recruitment of monocytes. We found that neutrophil-borne human neutrophil peptide 1 (HNP1, α-defensin) and platelet-derived CCL5 form heteromers. These heteromers stimulate monocyte adhesion through CCR5 ligation. We further determined structural features of HNP1-CCL5 heteromers and designed a stable peptide that could disturb proinflammatory HNP1-CCL5 interactions. This peptide attenuated monocyte and macrophage recruitment in a mouse model of myocardial infarction. These results establish the in vivo relevance of heteromers formed between proteins released from neutrophils and platelets and show the potential of targeting heteromer formation to resolve acute or chronic inflammation.


Assuntos
Plaquetas/metabolismo , Quimiocina CCL5/metabolismo , Monócitos/metabolismo , Neutrófilos/metabolismo , Multimerização Proteica , alfa-Defensinas/metabolismo , Adesão Celular , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Monócitos/citologia , Miocárdio/citologia , Neutrófilos/citologia , Ligação Proteica
18.
Leuk Lymphoma ; 45(10): 2161-3, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15370266

RESUMO

The incidence of mucormycosis, defined as systemic infection caused by fungi of the class Phycomycetes has been increasing over the past 2 decades, especially in profoundly immunocompromised hosts. We report a new case in a patient presenting with post-transplant high-grade non-Hodgkin's lymphoma who received a prolonged treatment with voriconazole and caspofungin for an invasive pulmonary aspergillosis. Definite diagnosis of mucormycosis was made by liver biopsy of nodules mimicking progressive lymphoma. The patient died 1 week after the diagnosis of mucormycosis despite the administration of liposomal amphotericin B. The role of voriconazole and caspofungin in the emergence of mucormycosis is discussed.


Assuntos
Antifúngicos/efeitos adversos , Aspergilose Broncopulmonar Alérgica/complicações , Transplante de Rim/efeitos adversos , Linfoma não Hodgkin/complicações , Mucormicose/etiologia , Anfotericina B/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Aspergilose Broncopulmonar Alérgica/etiologia , Caspofungina , Equinocandinas , Evolução Fatal , Feminino , Humanos , Lipopeptídeos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/etiologia , Pessoa de Meia-Idade , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Peptídeos Cíclicos/efeitos adversos , Pirimidinas/efeitos adversos , Falha de Tratamento , Triazóis/efeitos adversos , Voriconazol
20.
Aquat Toxicol ; 96(2): 85-9, 2010 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-19896729

RESUMO

A proteomic analysis combining peptide de novo sequencing and BLAST analysis was used to identify novel proteins involved in copper tolerance in the marine alga Scytosiphon gracilis (Phaeophyceae). Algal material was cultivated in seawater without copper (control) or supplemented with 100 microg L(-1) for 4 days, and protein extracts were separated by two-dimensional gel electrophoresis (2-DE). From the proteins obtained in the copper treatment, 25 over-expressed, 5 under-expressed and 5 proteins with no changes as compared with the control, were selected for sequencing. Tryptic-peptides obtained from 35 spots were analyzed by capillary liquid chromatography and tandem mass spectroscopy (capLC/MS/MS), and protein identity was determined by BLASTP. We identified 19 over-expressed proteins, including a chloroplast peroxiredoxin, a cytosolic phosphomannomutase, a cytosolic glyceraldehyde-3-phosphate dehydrogenase, 3 ABC transporters, a chaperonine, a subunit of the proteasome and a tRNA synthase, among others. The possible involvement of these over-expressed proteins in buffering oxidative stress and avoiding metal uptake in S. gracilis exposed to copper excess is discussed taking into consideration the information available for other plant models.


Assuntos
Proteínas de Algas/metabolismo , Cobre/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico/metabolismo , Phaeophyceae , Proteômica , Poluentes Químicos da Água/toxicidade , Biologia Marinha , Phaeophyceae/efeitos dos fármacos , Phaeophyceae/metabolismo , Estresse Fisiológico
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