RESUMO
Lake Dziani Dzaha (Mayotte Island, Indian Ocean) is a tropical thalassohaline lake which geochemical and biological conditions make it a unique aquatic ecosystem considered as a modern analogue of Precambrian environments. In the present study, we focused on the diversity of phytoplanktonic communities, which produce very high and stable biomass (mean2014-2015 = 652 ± 179 µg chlorophyll a L-1). As predicted by classical community ecology paradigms, and as observed in similar environments, a single species is expected to dominate the phytoplanktonic communities. To test this hypothesis, we sampled water column in the deepest part of the lake (18 m) during rainy and dry seasons for two consecutive years. Phytoplanktonic communities were characterized using a combination of metagenomic, microscopy-based and flow cytometry approaches, and we used statistical modeling to identify the environmental factors determining the abundance of dominant organisms. As hypothesized, the overall diversity of the phytoplanktonic communities was very low (15 OTUs), but we observed a co-dominance of two, and not only one, OTUs, viz., Arthrospira fusiformis (Cyanobacteria) and Picocystis salinarum (Chlorophyta). We observed a decrease in the abundance of these co-dominant taxa along the depth profile and identified the adverse environmental factors driving this decline. The functional traits measured on isolated strains of these two taxa (i.e., size, pigment composition, and concentration) are then compared and discussed to explain their capacity to cope with the extreme environmental conditions encountered in the aphotic, anoxic, and sulfidic layers of the water column of Lake Dziani Dzaha.
Assuntos
Clorófitas/crescimento & desenvolvimento , Lagos/microbiologia , Fitoplâncton/crescimento & desenvolvimento , Spirulina/crescimento & desenvolvimento , Biodiversidade , Biomassa , Clorofila A/metabolismo , Clorófitas/metabolismo , Ecossistema , Oceano Índico , Ilhas , Fitoplâncton/genética , Estações do Ano , Spirulina/metabolismoRESUMO
BACKGROUND: Actinic lentigos (AL) are benign hyperpigmented skin lesions associated with photoageing. Despite their high prevalence, biological mechanisms driving their formation remain unclear. OBJECTIVES: To provide new insights about the physiopathology of AL through a comprehensive description of their histological and molecular features. METHODS: Quantitative analysis of dermoscopic images was used to select AL containing elongated patterns, predicted to display a highly deformed dermal-epidermal junction (DEJ), on the back of the hands of 15 Caucasian women. Biopsies from lesional and adjacent nonlesional (NL) areas were processed for histological analysis or gene expression profiling. RESULTS: Histological staining confirmed a drastic deformation of the DEJ in AL, with deep epidermal invaginations into the dermis. Although the melanin content was significantly higher in AL compared with NL epidermis, the distribution of melanocytes along the DEJ was unchanged. Transcriptomic analysis revealed a signature of 529 genes differently expressed in AL vs. NL skin. Alteration of epidermal homeostasis was confirmed by the dysregulation of keratinocyte proliferation and differentiation markers. Surprisingly, canonical genes involved in melanogenesis were not significantly modulated in AL. A striking finding was the overexpression of a large group of genes involved in dermal extracellular matrix organization and remodelling. Dermal alterations were confirmed by immunolabellings on AL and NL sections. CONCLUSIONS: Drastic disorganization of the cutaneous structure in AL is accompanied by a specific molecular signature revealing alterations in both epidermal and dermal compartments. In particular, our results suggest that local modifications of the dermal extracellular matrix might contribute to hyperpigmentation in AL.
Assuntos
Matriz Extracelular/patologia , Lentigo/patologia , Transtornos de Fotossensibilidade/patologia , Pele/patologia , Idoso , Dorso , Dermoscopia , Epiderme/metabolismo , Matriz Extracelular/metabolismo , Feminino , Perfilação da Expressão Gênica , Genes/genética , Dermatoses da Mão/genética , Dermatoses da Mão/metabolismo , Dermatoses da Mão/patologia , Humanos , Lentigo/genética , Melaninas/metabolismo , Melanócitos/metabolismo , Pessoa de Meia-Idade , Transtornos de Fotossensibilidade/genética , Pele/metabolismo , Transcriptoma/genética , Regulação para Cima/genéticaRESUMO
BACKGROUND: Cryptosporidium spp. is a ubiquitous parasite affecting humans as well as domestic and wild vertebrates, causing diarrhea in both immunocompetent and immunocompromised hosts worldwide. Its transmission occurs primarily by the fecal-oral route. In humans, C. parvum and C. hominis are the most prevalent species, whereas immunocompetent and immunocompromised individuals can also be infected by other zoonotic species. Renal transplant patients are prone to develop cryptosporidiosis, which can induce severe and life-threatening diarrhea. CASE PRESENTATION: We report here a series of nearly concomitant cases of acute symptomatic cryptosporidiosis in three renal transplant patients attending the Strasbourg University Hospital Nephrology Unit. The clinical presentation was persistent diarrhea and acute renal failure. The diagnosis was confirmed by microscopic stool examination using a modified Ziehl-Neelsen staining method and species identification by molecular tools. All patients were treated with nitazoxanide and recovered from diarrhea after 14 days of therapy. CONCLUSION: Genotypic species identification was not consistent with an epidemic context, thus underlining the need for genotyping to monitor at risk patients.
Assuntos
Infecção Hospitalar/parasitologia , Criptosporidiose/transmissão , Cryptosporidium/patogenicidade , Transplante de Rim , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/parasitologia , Adulto , Animais , Coccidiostáticos/uso terapêutico , Criptosporidiose/complicações , Criptosporidiose/tratamento farmacológico , Cryptosporidium/genética , Diarreia/etiologia , Diarreia/parasitologia , Fezes/parasitologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Nitrocompostos , Tiazóis/uso terapêuticoRESUMO
The risk of fractures after kidney transplantation is high. Hyperparathyroidism frequently persists after successful kidney transplantation and contributes to bone loss, but its impact on fracture has not been demonstrated. This longitudinal study was designed to evaluate hyperparathyroidism and its associations with mineral disorders and fractures in the 5 posttransplant years. We retrospectively analyzed 143 consecutive patients who underwent kidney transplantation between August 2004 and April 2006. The biochemical parameters were determined at transplantation and at 3, 12 and 60 months posttransplantation, and fractures were recorded. The median intact parathyroid hormone (PTH) level was 334 ng/L (interquartile 151-642) at the time of transplantation and 123 ng/L (interquartile 75-224) at 3 months. Thirty fractures occurred in 22 patients. The receiver operating characteristic (ROC) curve analysis for PTH at 3 months (area under the ROC curve = 0.711, p = 0.002) showed that a good threshold for predicting fractures was 130 ng/L (sensitivity = 81%, specificity = 57%). In a multivariable analysis, independent risk factors for fracture were PTH >130 ng/L at 3 months (adjusted hazard ratio [AHR] = 7.5, 95% CI 2.18-25.50), and pretransplant osteopenia (AHR = 2.7, 95% CI 1.07-7.26). In summary, this study demonstrates for the first time that persistent hyperparathyroidism is an independent risk factor for fractures after kidney transplantation.
Assuntos
Calcificação Fisiológica , Fraturas Ósseas/etiologia , Hiperparatireoidismo/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Hormônio Paratireóideo/sangue , Complicações Pós-Operatórias , Adulto , Idoso , Feminino , Seguimentos , Fraturas Ósseas/sangue , Fraturas Ósseas/diagnóstico , Taxa de Filtração Glomerular , Humanos , Hiperparatireoidismo/sangue , Hiperparatireoidismo/diagnóstico , Testes de Função Renal , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Methylmercury (MeHg) determinations in hake, its food-chain, and the surrounding waters and sediments allowed us to show that the higher length or age normalized mercury concentrations of Northwestern Mediterranean (Gulf of Lions: GoL) muscle hakes compared to its Northeastern Atlantic (Bay of Biscay: BoB) counterpart are due to both biotic and abiotic differences between their ecosystems. Bioenergetic modeling reveals that the slower growth rate of Mediterranean hake favors the MeHg bioaccumulation in the fish muscle and explains most of the difference between GOL and BoB hake populations. In addition, the waters of the Mediterranean hake habitat favor a higher MeHg exposition, due to the upper position of the thermohalocline, where MeHg is formed. Furthermore, we show that, within the Mediterranean hake population, a major increase in the biomagnification power (the slope of the relationships between logMeHg and δ(15)N), from 0.36 up to 1.12, occurs when individuals enter adulthood, resulting from the combined effects of lowering growth rate and change in feeding habits. Finally, δ(15)N normalized Hg concentrations indicate that the highest Hg concentrations are for hake from the shelf edge and the lowest are for hake from the Rhône prodelta area, suggesting a lower Hg bioavailability in inshore environments, consistent with MeHg distributions in water, sediment, and preys.
Assuntos
Cadeia Alimentar , Gadiformes/crescimento & desenvolvimento , Compostos de Metilmercúrio/análise , Animais , Oceano Atlântico , Disponibilidade Biológica , Feminino , Sedimentos Geológicos/análise , Masculino , Mar Mediterrâneo , Músculos/química , Água/análiseRESUMO
BACKGROUND: Interventions simultaneously targeting multiple risk factors and mechanisms are most likely to be effective in preventing cognitive impairment. This was indicated in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) testing a multidomain lifestyle intervention among at-risk individuals. The importance of medical food at the early symptomatic disease stage, prodromal Alzheimer's disease (AD), was emphasized in the LipiDiDiet trial. The feasibility and effects of multimodal interventions in prodromal AD are unclear. OBJECTIVES: To evaluate the feasibility of an adapted FINGER-based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD. METHODS: MIND-ADmini is a multinational proof-of-concept 6-month randomized controlled trial (RCT), with four trial sites (Sweden, Finland, Germany, France). The trial targeted individuals with prodromal AD defined using the International Working Group-1 criteria, and with vascular or lifestyle-related risk factors. The parallel-group RCT includes three arms: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); 2) multimodal lifestyle intervention+medical food (Fortasyn Connect); and 3) regular health advice/care (control group). Primary outcomes are feasibility and adherence. Secondary outcomes are adherence to the individual intervention domains and healthy lifestyle changes. RESULTS: Screening began on 28 September 2017 and was completed on 21 May 2019. Altogether 93 participants were randomized and enrolled. The intervention proceeded as planned. CONCLUSIONS: For the first time, this pilot trial tests the feasibility and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. It can serve as a model for combination therapy trials (non-pharma, nutrition-based and/or pharmacological interventions).
Assuntos
Doença de Alzheimer , Transtornos Cognitivos , Disfunção Cognitiva , Idoso , Doença de Alzheimer/prevenção & controle , Transtornos Cognitivos/prevenção & controle , Disfunção Cognitiva/prevenção & controle , Humanos , Estilo de Vida , Projetos PilotoRESUMO
The differential allocation hypothesis predicts that females modify their investment in a breeding attempt according to its reproductive value. One prediction of this hypothesis is that females will increase reproductive investment when mated to high-quality males. In birds, it was shown that females can modulate pre-hatch reproductive investment by manipulating egg and clutch sizes and/or the concentrations of egg internal compounds according to paternal attractiveness. However, the differential allocation of immune factors has seldom been considered, particularly with an experimental approach. The carotenoid-based ornaments can function as reliable signals of quality, indicating better immunity or ability to resist parasites. Thus, numerous studies show that females use the expression of carotenoid-based colour when choosing mates; but the influence of this paternal coloration on maternal investment decisions has seldom been considered and has only been experimentally studied with artificial manipulation of male coloration. Here, we used dietary carotenoid provisioning to manipulate male mallard (Anas platyrhynchos) bill coloration, a sexually selected trait, and followed female investment. We show that an increase of male bill coloration positively influenced egg mass and albumen lysozyme concentration. By contrast, yolk carotenoid concentration was not affected by paternal ornamentation. Maternal decisions highlighted in this study may influence chick survival and compel males to maintain carotenoid-based coloration from the mate-choice period until egg-laying has been finished.
Assuntos
Bico/fisiologia , Carotenoides , Patos/fisiologia , Preferência de Acasalamento Animal/fisiologia , Pigmentos Biológicos , Animais , Feminino , MasculinoRESUMO
Cyanobacteria are able to synthesize a high diversity of natural compounds that account for their success in the colonization of a variety of ecological niches. Many of them have beneficial properties. The mud from the thermal baths of Balaruc-Les-Bains, one of the oldest thermal baths in France, has long been recognized as a healing treatment for arthro-rheumatic diseases. To characterize the cyanobacteria living in these muds, several strains were isolated from the water column and biofilms of the retention basin and analyzed using a polyphasic approach. Morphological, ultrastructural and molecular (16S rRNA gene and 16S-23S ITS region sequencing) methods were employed to identify nine cyanobacterial strains belonging to the orders Chroococcales, Synechococcales, Oscillatoriales and Nostocales. The combination of morphological and genetic characteristics supported the description of a new genus and species with the type species as Pseudochroococcus coutei. The taxonomic diversity in the muds from Thermes de Balaruc-Les-Bains appears higher than previously documented, providing new candidate taxa for their observed therapeutic properties.
RESUMO
Introduction: Chlamydia trachomatis (CT) infection is the commonest bacterial sexually transmitted infection (STI) in the world. Often asymptomatic, it can lead to significant complications in women. In France, since 2003, systematic screening for CT in STI center has been recommended for women aged less than 25 year. The main objective of this study was to determine CT prevalence in patients attending STI centers in Reunion Island. The second objective was to explore the determinants of this infection. Method: A cross-sectional survey using an anonymous questionnaire was conducted among women attending STI center in two hospitals in western and southern Reunion Island during one year. All women who had performed a CT PCR, based on vaginal self-swabs, were included. Results: Among the 620 patients tested, the prevalence of infection was 6.6% (95% CI [4.7-8.6]). By age group, the highest prevalence was between 12 and 17 years with 14.3% positive tests compared to 7.5% and 3.9% respectively in 18-24 and 25-67 year age group (p = 0.003). The risk factors for CT were a young age (p = 0.02), a first sexual intercourse between 11 and 14 years old (p = 0.01), lack of previous STI screening history (p = 0.02), and the following motives for seeking screening: "partner unfaithfulness" (p = 0.01) and "infected partner" (p = 0.02). Conclusion: This study highlights the high prevalence of CT among Reunionese minors. A more systematic screening and a reinforcement of STI awareness among young people in Reunion Island seem to be essential.
Assuntos
Infecções por Chlamydia , Infecções Sexualmente Transmissíveis , Adolescente , Criança , Pré-Escolar , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis , Estudos Transversais , Feminino , Humanos , Prevalência , Reunião/epidemiologia , Fatores de Risco , Infecções Sexualmente Transmissíveis/epidemiologiaRESUMO
OBJECTIVES: To assess (without comparison versus controls) the efficacy of a sophrology protocol adapted to disabling subjective tinnitus, in diminishing the handicap induced by perception of tinnitus. MATERIALS AND METHODS: One hundred and forty consecutive patients, aged 18-83 years, underwent a protocol comprising 6-8 sessions of sophrology over a 2-4 month period. Impact was assessed on pre- to post-treatment progression on the Tinnitus Handicap Inventory (THI), a validated questionnaire measuring handicap induced by tinnitus. RESULTS: Mean THI scores improved, by >20 points in 59.2% of cases (i.e., clinically significant decrease). Improvement was independent of tinnitus duration (>versus<6 months) and origin (acoustic trauma versus emotional shock), and concerned all 3 THI subscales (functional, catastrophic and emotional). CONCLUSION: The present sophrology protocol, dedicated to subjective tinnitus, reduced intrusiveness. Further studies with a control group are needed to confirm efficacy as compared to waiting list or other validated treatments such as cognitive behavioral therapies.
Assuntos
Terapias Mente-Corpo , Zumbido/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
The saline-alkaline crater-lake Dziani Dzaha (Mayotte, Indian Ocean) is dominated by the bloom-forming cyanobacterium Arthrospira. However, the rest of the phototrophic community remains underexplored because of their minute dimension or lower biomass. To characterize the phototrophic microorganisms living in this ecosystem considered as a modern analog of Precambrian environments, several strains were isolated from the water column and stromatolites and analyzed using the polyphasic approach. Based on morphological, ultrastructural and molecular (16S rRNA gene, 18S rRNA gene, 16S-23S internal transcribed spacer (ITS) region and cpcBA-IGS locus) methods, seven filamentous cyanobacteria and the prasinophyte Picocystis salinarum were identified. Two new genera and four new cyanobacteria species belonging to the orders Oscillatoriales (Desertifilum dzianense sp. nov.) and Synechococcales (Sodalinema komarekii gen. nov., sp. nov., Sodaleptolyngbya stromatolitii gen. nov., sp. nov. and Haloleptolyngbya elongata sp. nov.) were described. This approach also allowed to identify Arthrospira fusiformis with exclusively straight trichomes instead of the spirally coiled form commonly observed in the genus. This study evidenced the importance of using the polyphasic approach to solve the complex taxonomy of cyanobacteria and to study algal assemblages from unexplored ecosystems.
Assuntos
Cianobactérias/classificação , Lagos/microbiologia , Oscillatoria/isolamento & purificação , Processos Fototróficos/fisiologia , Spirulina/isolamento & purificação , Synechococcus/isolamento & purificação , Biomassa , Comores , Cianobactérias/genética , Cianobactérias/isolamento & purificação , DNA Bacteriano/genética , DNA Espaçador Ribossômico/genética , Oceano Índico , Lagos/química , Oscillatoria/classificação , Oscillatoria/genética , Filogenia , RNA Ribossômico 16S/genética , Salinidade , Análise de Sequência de DNA , Spirulina/classificação , Spirulina/genética , Synechococcus/classificação , Synechococcus/genéticaRESUMO
The first 12 cell divisions of Xenopus laevis embryos do not require gene transcription. This means that the regulation of gene expression during this period is controlled at post transcriptional levels and makes Xenopus early development a potentially interesting biological system with which to study the mechanisms involved. We describe here the stability characteristics of several maternal Xenopus mRNAs which are deadenylated soon after fertilisation (J. Paris and M. Philippe, Dev. Biol., in press). We show that these mRNAs were only degraded in the embryo after the midblastula transition (MBT), when gene transcription was initiated. The kinetics with which the deadenylated maternal mRNAs decreased in the post-MBT embryos showed sequence specificity. The degradation of these mRNAs after the MBT was inhibited by cycloheximide but was not affected by dactinomycin. Therefore, the destabilization of these mRNAs does not appear to be initiated by new embryonic gene transcripts. Sequence comparisons of the 3' untranslated region of these mRNAs identified several motifs which may be involved in the posttranscriptional control of these gene products.
Assuntos
Embrião não Mamífero/fisiologia , Biossíntese de Proteínas , RNA Mensageiro/genética , Transcrição Gênica , Animais , Sequência de Bases , Northern Blotting , Divisão Celular , Embrião não Mamífero/citologia , Feminino , Cinética , Dados de Sequência Molecular , RNA/genética , RNA/isolamento & purificação , RNA Mensageiro/metabolismo , Homologia de Sequência do Ácido Nucleico , Xenopus laevisRESUMO
The clinical phenotype of patients with congenital dysfibrinogenaemia is highly heterogeneous, from absence of symptoms to mild bleeding, or thrombosis. A few mutations are associated with a specific phenotype, but generally the clinical course is not predictable. We investigated whether fibrin clot properties are correlated with the patient's phenotype and/or genotype. Ex vivo plasma fibrin clot characteristics, including turbidity, fibrinolysis, clot permeability and fibrin fibre density assessed by laser scanner confocal microscopy were investigated in 24 genotyped patients with congenital dysfibrinogenaemia compared to normal pool plasma. Compared to normal pool plasma, the patients were characterised by slower fibrin polymerisation (lag time, 345.10 ± 22.98 vs. 166.00s), thinner fibrin fibres (maximum absorbance, 0.15 ± 0.01 vs. 0.31), prolonged clot lysis time (23.72 ± 0.97 vs. 20.32 min) and larger clot pore size (21.5×10(-9) ± 4.48×10(-9) vs. 7.96×10(-9)cm(2)). Laser scanning confocal microscopy images confirmed disorganised fibrin networks in all patients. Patients with tendency to bleed showed an increased permeability compared to asymptomatic patients (p=0.01) and to patients with a thrombotic history (p=0.02) while patients with thrombotic history had a tendency to have a prolonged clot lysis time. Fibrin clot properties were similar among hotspot mutations. Further studies including a larger number of patients are needed to evaluate whether analysis of permeability and clot lysis time may help to distinguish the clinical phenotype in these patients and to assess differences according to the genotype.
Assuntos
Anemia Diseritropoética Congênita/sangue , Anemia Diseritropoética Congênita/patologia , Tempo de Lise do Coágulo de Fibrina/métodos , Fibrina/metabolismo , Fibrina/ultraestrutura , Adulto , Idoso , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/ultraestrutura , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
PURPOSE: In view of the increasing number of patients treated with breast-conserving treatment (BCT) for ductal carcinoma-in-situ (DCIS), risk factors for recurrence and metastasis should be identified. PATIENTS AND METHODS: Clinical and pathologic characteristics from patients with DCIS in the European Organization for Research and Treatment of Cancer trial 10853 (excision with or without radiotherapy) were related to the risk of recurrence. Pathologic features were derived from a central review of 863 of the 1,010 randomized cases (85%). The median follow-up was 5.4 years. RESULTS: Factors associated with an increased risk of local recurrence in the multivariate analysis were young age (< or = 40 years) (hazard ratio, 2.14; P =.02), symptomatic detection of DCIS (hazard ratio, 1.80; P =.008), growth pattern (solid and cribriform) (hazard ratios, 2.67 and 2.69, respectively; P =.012), involved margins (hazard ratio, 2.07; P =.0008), and treatment by local excision alone (hazard ratio, 1.74; P =.009). The risk of invasive recurrence was not related to the histologic type of DCIS (P =.63), but the risk of distant metastasis was significantly higher in poorly differentiated DCIS compared with well-differentiated DCIS (hazard ratio, 6.57; P =.01). CONCLUSION: Patients with poorly differentiated DCIS have a high risk of distant metastasis after invasive local recurrence. Margin status is the most important factor in the success of BCT for DCIS; additionally, young age and symptomatic detection of DCIS have negative prognostic value.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/secundário , Carcinoma Intraductal não Infiltrante/cirurgia , Mastectomia Segmentar , Recidiva Local de Neoplasia , Adulto , Idade de Início , Idoso , Progressão da Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
PURPOSE: Thirty percent of women with node-negative breast cancer will have a recurrence within 10 years after diagnosis. Molecular markers may identify those patients and predict whether they benefit from adjuvant therapy. The European Organization for Research and Treatment of Cancer (EORTC) conducted a randomized trial (EORTC 10854) to compare perioperative treatment with one course of fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus no further therapy. We studied tumors from premenopausal patients with node-negative breast cancer randomized in this trial to determine whether p53 accumulation, c-erbB-2 expression, percentage of Ki-67-positive cells, estrogen receptor (ER-immunoassay [IA]), progesterone receptor (PR-IA), and angiogenesis could be used as prognostic factors and predictors of responsiveness to adjuvant chemotherapy. PATIENTS AND METHODS: Paraffin-embedded tumor specimens from 441 premenopausal women with node-negative breast cancer were collected from the larger EORTC trial. Paraffin sections from the tumors were analyzed for immunohistochemical expression of p53, c-erbB-2, Ki-67, ER, PR, and angiogenesis. RESULTS: Patients with p53-negative tumors showed a significant benefit from perioperative chemotherapy (P < .01), whereas patients who had p53-positive tumors did not (P = .80). At a median follow-up time of 49 months, univariate analyses for disease-free survival (DFS) failed to show prognostic value for p53, c-erbB-2 and angiogenesis. Both univariate and multivariate results showed Ki-67 positivity, ER-IA negativity, and a younger age to be associated with a worse prognosis. CONCLUSION: p53 accumulation was associated with a poor response to one perioperative course of FAC chemotherapy. Ki-67, ER-IA, and age are important prognostic factors in premenopausal women with node-negative breast cancer.
Assuntos
Neoplasias da Mama/metabolismo , Proteínas de Neoplasias/metabolismo , Pré-Menopausa , Proteína Supressora de Tumor p53/metabolismo , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Antígeno Ki-67/análise , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Taxa de SobrevidaRESUMO
Follicular lymphomas (FL) are closely associated with a t(14;18)(q32;q21) translocation, leading to a bcl2 protein over-production. This translocation probably constitutes a very early step in the development of the disease. Besides the cytogenetic assay, t(14;18) detection can be achieved using either Southern blot or polymerase chain reaction (PCR). Since 1990, several publications have reported discrepancies between the results of cytogenetic and molecular analysis of t(14;18). Using methods able to explore long DNA fragments, several authors reported breakpoints located outside the usual breakpoint regions. However, these techniques cannot be easily used in routine. The aim of this study was to develop a simple PCR assay to amplify rearrangements usually not detected in FL. We selected a group of 83 patients with a t(14;18) on cytogenetic analysis: using usual probes and primers, 54/83 (65.1%) showed a MBR rearrangement, 7/83 (8.4%) were mcr positive and 22/83 (26.5%) remained negative. Among these 22 rearrangements, nine could be detected using this new PCR assay. Four breakpoints were located in a 20 bp area suggesting a recurrent breakpoint cluster close to an Alu repetitive sequence. Finally, remaining negative cases (13/83, 15.6%) suggest that other breakpoints are located between the MBR and mcr regions.
Assuntos
Cromossomos Humanos Par 18 , Linfoma Folicular/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Translocação Genética , Sequência de Bases , Southern Blotting , DNA de Neoplasias/análise , Humanos , Dados de Sequência Molecular , Família Multigênica , Reação em Cadeia da Polimerase , Mapeamento por RestriçãoRESUMO
The t(14;18)(q32;q21) translocation is the most common translocation in B cell malignancies being found in 80% of follicular lymphomas and about 20% of diffuse large B cell lymphomas. Only rare cases of de novo acute B cell lymphoblastic leukemia with t(14;18) have been described. We describe five cases of this entity which appears to have very homogeneous clinical, phenotypic and genotypic features. None of these patients had prior history of follicular lymphoma. The disease was characterized by acute clinical features with nodal and/or extranodal disease, massive bone marrow infiltration and rapid increase of circulating blast cells of mature B cell phenotype. All patients disclosed complex chromosomal and molecular abnormalities involving at least the BCL-2 and c-MYC genes. Furthermore, three patients had evidence of BCL-6 involvement and one patient had a p53 mutation. Despite intensive chemotherapy, including for two patients allogeneic bone marrow transplantation in first complete remission, all patients died within a few months. Neuro-meningeal relapse occurred in three of the five patients in spite of neuro-meningeal prophylaxis. De novo leukemia/lymphoma with t(14;18) is a rare entity with a very poor prognosis. Whether early bone marrow transplant could modify the natural history of the disease remains to be determined. An intensive neuro-meningeal prophylaxis appears to be mandatory in these patients.
Assuntos
Linfoma de Burkitt/genética , Cromossomos Humanos Par 14/ultraestrutura , Cromossomos Humanos Par 18/ultraestrutura , Linfoma de Células B/genética , Translocação Genética , Adulto , Antineoplásicos/uso terapêutico , Crise Blástica/tratamento farmacológico , Crise Blástica/genética , Crise Blástica/patologia , Medula Óssea/patologia , Transplante de Medula Óssea , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/patologia , Linfoma de Burkitt/terapia , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , DNA de Neoplasias/genética , Proteínas de Ligação a DNA/genética , Progressão da Doença , Feminino , Genes bcl-2 , Genes myc , Genes p53 , Humanos , Imunofenotipagem , Infiltração Leucêmica , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Linfoma de Células B/terapia , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/genética , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Masculino , Meninges/patologia , Pessoa de Meia-Idade , Células Neoplásicas Circulantes , Prognóstico , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-6 , Recidiva , Terapia de Salvação , Fatores de Transcrição/genética , Falha de TratamentoRESUMO
Translocations involving the BCL-6 gene are frequently observed in diffuse large B cell lymphoma, but have rarely been reported in follicular lymphoma (FL). We studied a distinct cohort of FLs with a 3q27/BCL-6 gene rearrangement, but lacking the t(14;18) translocation. In 13/15 cases, translocations involved the 3q27 and the 14q32 regions. All cases displayed a marked follicular growth pattern and, in some instances, a monocytoid component. Tumor cells were CD5(-) CD20(+) CD23(-) CD43(-) BCL-6(+), and in the main CD10 negative (n = 10, 71%) and BCL-2 negative (n = 11, 78%). When compared to 20 typical t(14;18)(+) FLs, the presence of large follicles (P = 0.01) and a CD10(-)/BCL-2(-) phenotype were more frequently observed (P = 0.001) in our cohort. Clonal mutations arising in the BCL-6 first intron were observed in 5/7 cases with evidence of intraclonal heterogeneity, consistent with a germinal center origin. No significant difference was found in comparison to t(14;18)(+) FL regarding age, sex, performance status, bone marrow involvement or overall survival. However, in the 3q27(+) FL group, a stage III/IV disease and a bulky mass were less frequently observed. This study indicates that 3q27(+) FL without t(14;18) translocation have peculiar clinico-pathologic features and may correspond to a rare and distinct subtype of lymphoma originating from the germinal center.
Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , Proteínas de Ligação a DNA/genética , Rearranjo Gênico , Linfoma Folicular/genética , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição/genética , Translocação Genética , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Cromossomos Humanos Par 3/genética , Estudos de Coortes , Análise Mutacional de DNA , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Técnicas Imunoenzimáticas , Imunofenotipagem , Cariotipagem , Linfoma Folicular/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6 , Taxa de Sobrevida , Fatores de Transcrição/metabolismoRESUMO
Young French children have 45,000,000 domestic pets, cats and dogs being widely prevalent (40%). Injuries due to domestic animals, especially bites, in particular from dogs, represent 1.9% of all children's injuries. On the quality of first aid in the field, i.e., whether the treatment is the first line in surgical specialized service or not, if it is a vital emergency, will depend the possibility of immediate complications, which include local superinfection (15%), functionals and further aesthetic sequelae. Some injuries due to large animals carry a polytraumatism, which should be treated like all polytraumatisms, whatever the aetiology. Learning to know and respect animals and their needs should remain the priority of families to avoid unexpected injury. Families also need to take charge of the responsible animal.