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1.
Ann Pharm Fr ; 78(1): 58-69, 2020 Jan.
Artículo en Francés | MEDLINE | ID: mdl-31564419

RESUMEN

CONTEXT: There is more and more evidence about the roles and impacts of the pharmacist. Health decision makers, managers, clinicians and patients need evidence to support an appropriate allocation of funds to different models of practice. OBJECTIVES: The main objective is to present an inventory of the roles and impacts of pharmaceutical activity in the international literature. METHODS: Review of literature. The articles related to the pharmacist's roles and impacts were selected according to a reproducible research strategy from 1990 to the present day (French/English with description of the intervention and impacts, where applicable) and a standard operating procedure. The following variables were extracted: author, country, specifications, pharmaceutical activities, care programs, targeted pathologies, impacts according to eight markers (mortality, morbidity, costs, adverse events, medication errors, compliance, satisfaction, others) and quality score. Only descriptive statistics were performed. RESULTS: As of February 1st, 2019, we recorded 2424 articles divided into 100 subjects (41 pharmaceutical activities, 30 pathologies, 29 care programs). Studies come from the United States (46.66%), multiple countries (8.00%), Canada (7.67%), France (6.06%), the United Kingdom (5.19%), Australia (3.50%) and other countries (22.92%). Studies are cross-sectional (47.55%), retrospective (33.68%) and prospective (17.87%) or non-categorized (<1%). The markers associated with the pharmacist's activity concern morbidity (23.12%), medication errors (11.82%), satisfaction (7.13%), compliance (6.06%), costs (5.47%), adverse events (3.74%), mortality (1.36%), and other indicators (41.31%). The studies have 6763 descriptive parameters and 5224 impact parameters (60.42% are positive, 38.55% are neutral and 1.03% are negative). CONCLUSION: This literature review confirms the roles and impacts of the pharmaceutical activity both in the pharmacy and in the hospital. A majority of the pharmaceutical interventions studied have positive impacts. It is essential to consider evidence about the roles and impacts of the pharmaceutical activities to take full advantage of the pharmacist's expertise in healthcare.


Asunto(s)
Bibliometría , Farmacéuticos , Farmacología/estadística & datos numéricos , Rol Profesional , Australia , Costos de los Medicamentos/estadística & datos numéricos , Quimioterapia/estadística & datos numéricos , Europa (Continente) , Cumplimiento de la Medicación/estadística & datos numéricos , Errores de Medicación/estadística & datos numéricos , América del Norte , Farmacias/estadística & datos numéricos , Servicio de Farmacia en Hospital/estadística & datos numéricos , Investigación
2.
Phytopathology ; 109(3): 456-468, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30145938

RESUMEN

Coniferiporia sulphurascens is a facultative fungal pathogen that causes laminated root rot (LRR) in commercially important coniferous species worldwide. This fungus spreads primarily by way of vegetative mycelium transferring at points of contact between infected and healthy roots. Successful intervention to control LRR requires a better understanding of the population structure and genetic variability of C. sulphurascens. In this study, we investigated the population genetic structure and origin of C. sulphurascens populations in western North America and eastern Eurasia collected from multiple coniferous hosts. By analyzing the small and large mitochondrial ribosomal RNA subunit genes combined with six nuclear loci (internal transcribed spacer region, actin, RNA polymerase II largest subunit, RNA polymerase II second-largest subunit, laccase-like multicopper oxidase, and translation elongation factor 1-α), we observed that none of the alleles among the loci were shared between North American (NA) and Eurasian C. sulphurascens populations. In total, 55 multilocus genotypes (MLGs) were retrieved in C. sulphurascens isolates occurring in these two continental regions. Of these, 41 MLGs were observed among 58 isolates collected from widespread locations in British Columbia (Canada) and the northwestern United States, while 14 MLGs were observed among 16 isolates sampled in Siberia and Japan. Our data showed that the levels of genetic differentiation between the NA and Eurasian populations are much greater than the populations from within each continental region; the two continental populations formed clearly divergent phylogenetic clades or lineages since they were separated approximately 7.5 million years ago. Moreover, the Eurasian population could be the source of the NA population. Our study indicates the existence of cryptic diversity in this pathogen species, and strongly suggests that the NA and Eurasian populations represent two lineages, which have progressively diverged from each other in allopatry.


Asunto(s)
Variación Genética , Enfermedades de las Plantas , Colombia Británica , Japón , América del Norte , Noroeste de Estados Unidos , Filogenia , Enfermedades de las Plantas/microbiología , Análisis de Secuencia de ADN
3.
Ann Oncol ; 29(4): 1056-1062, 2018 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29145561

RESUMEN

Background: CD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Several CD73 inhibitors and adenosine receptor antagonists are being evaluated in phase I clinical trials. Patients and methods: Full-face sections from formalin-fixed paraffin-embedded primary breast tumors from 122 samples of triple-negative breast cancer (TNBC) from the BIG 02-98 adjuvant phase III clinical trial were included in our analysis. Using multiplex immunofluorescence and image analysis, we assessed CD73 protein expression on tumor cells, tumor-infiltrating leukocytes and stromal cells. We investigated the associations between CD73 protein expression with disease-free survival (DFS), overall survival (OS) and the extent of tumor immune infiltration. Results: Our results demonstrated that high levels of CD73 expression on epithelial tumor cells were significantly associated with reduced DFS, OS and negatively correlated with tumor immune infiltration (Spearman's R= -0.50, P < 0.0001). Patients with high levels of CD73 and low levels of tumor-infiltrating leukocytes had the worse clinical outcome. Conclusions: Taken together, our study provides further support that CD73 expression is associated with a poor prognosis and reduced anti-tumor immunity in human TNBC and that targeting CD73 could be a promising strategy to reprogram the tumor microenvironment in this BC subtype.


Asunto(s)
5'-Nucleotidasa/inmunología , Neoplasias de la Mama Triple Negativas/inmunología , Anticuerpos Monoclonales/inmunología , Supervivencia sin Enfermedad , Femenino , Proteínas Ligadas a GPI/inmunología , Humanos , Pronóstico
4.
Hum Reprod ; 29(5): 953-63, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24578476

RESUMEN

STUDY QUESTION: Is hysterosalpingosonography (sono-HSG) an accurate test for diagnosing tubal occlusion in subfertile women and how does it perform compared with hysterosalpingography (HSG)? SUMMARY ANSWER: sono-HSG is an accurate test for diagnosing tubal occlusion and performs similarly to HSG. WHAT IS KNOWN ALREADY: sono-HSG and HSG are both short, well-tolerated outpatient procedures. However, sono-HSG has the advantage over HSG of obviating ionizing radiation and the risk of iodine allergy, being associated with a greater sensitivity and specificity in detecting anomalies of the uterine cavity and permitting concomitant visualization of the ovaries and myometrium. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis of studies published in any language before 14 November 2012 were performed. All studies assessing the accuracy of sono-HSG for diagnosing tubal occlusion in a subfertile female population were considered. PARTICIPANTS/MATERIALS, SETTING, METHODS: We searched Medline, Embase, Cochrane Library, Web of Science and Biosis as well as related articles, citations and reference lists. Diagnostic studies were eligible if they compared sono-HSG (±HSG) to laparoscopy with chromotubation in women suffering from subfertility. Two authors independently screened for eligibility, extracted data and assessed the quality of included studies. Risk of bias and applicability concerns were investigated according to the Quality Assessment of Diagnostic Accuracy Study (QUADAS-2). Bivariate random-effects models were used to estimate pooled sensitivity and specificity with their 95% confidence intervals (95% CIs), to generate summary receiver operating characteristic curves and to evaluate sources of heterogeneity. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 4221 citations identified, 30 studies were eligible. Of the latter, 28 reported results per individual tube and were included in the meta-analysis, representing a total of 1551 women and 2740 tubes. In nine studies, all participants underwent HSG in addition to sono-HSG and laparoscopy, allowing direct comparison of the accuracy of sono-HSG and HSG. Pooled estimates of sensitivity and specificity of sono-HSG were 0.92 (95% CI: 0.82-0.96) and 0.95 (95% CI: 0.90-0.97), respectively. In nine studies (582 women, 1055 tubes), sono-HSG and HSG were both compared with laparoscopy, giving pooled estimates of sensitivity and specificity of 0.95 (95% CI: 0.78-0.99) and 0.93 (95% CI: 0.89-0.96) for sono-HSG, and 0.94 (95% CI: 0.74-0.99) and 0.92 (95% CI: 0.87-0.95) for HSG, respectively. Doppler sonography was associated with significantly greater sensitivity and specificity of sono-HSG compared with its non-use (0.93 and 0.95 versus 0.86 and 0.89, respectively, P = 0.0497). Sensitivity analysis regarding methodological quality of studies was consistent with these findings. We also found no benefit of the commercially available contrast media over saline solution in regard to the diagnostic accuracy of sono-HSG. LIMITATIONS, REASONS FOR CAUTION: Methodological quality varied greatly between studies. However, sensitivity analysis, taking methodological quality of studies into account, did not modify the results. This systematic review did not allow the distinction between distal and proximal occlusion. This could be interesting to take into account in further studies, as the performance of the test may differ for each localization. WIDER IMPLICATIONS OF THE FINDINGS: Given our findings and the known benefits of sono-HSG over HSG in the context of subfertility, sono-HSG should replace HSG in the initial workup of subfertile couples. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by personal funds. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: This review has been registered at PROSPERO: Registration number #CRD42013003829.


Asunto(s)
Endosonografía/métodos , Enfermedades de las Trompas Uterinas/diagnóstico por imagen , Infertilidad Femenina/diagnóstico por imagen , Enfermedades de las Trompas Uterinas/complicaciones , Femenino , Humanos , Infertilidad Femenina/etiología
5.
J Appl Microbiol ; 117(2): 597-609, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24849008

RESUMEN

AIMS: The aim of this study was to characterize Escherichia fergusonii and Escherichia albertii isolated from water. METHODS AND RESULTS: The characterization of E. fergusonii and E. albertii isolated from water was determined using an Escherichia coli-specific uidA PCR, a tuf PCR, and with phylogenetic analysis using three housekeeping genes (adk, gyrB, and recA) from the E. coli MLST scheme, selected for their ability to discriminate among all Escherichia species. Among the 527 isolates tested, 25 (4·7%) were uidA PCR negative and tuf PCR positive. Phylogenetic analysis using adk, gyrB and recA genes showed that 6, 18 and 1 of these 25 non-E. coli Escherichia spp. isolates grouped with reference strains of E. fergusonii, E. albertii, and E. coli, respectively. Finally, the 25 non-E. coli Escherichia spp. strains isolated were investigated for the presence of pathogenic factors, comprising intimin (eae gene), cytolethal distending toxin (cdtB gene) and shiga toxin (stx gene). With the PCR primers used, the presence of eae and stx genes was not detected. However, cdtB genes types I/IV were detected for 3 (16·7%) E. albertii strains, whereas 15 of 18 (83·3%) possessed the cdtB gene types II/III/V. CONCLUSIONS: These results showed that MLST scheme allows a more accurate identification of non-E. coli species than phenotypic tests. We also showed that E. fergusonii and E. albertii represent, respectively, 0·8 and 2·5% of all Escherichia species isolated and the pathogenic cdtB genes were present in 83·3% of these strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The data presented in this study provided an efficient way to correctly identify non-E. coli species contributing to our understanding of the risks associated with Escherichia species in water consumed by humans and animals. Furthermore, the results give an insight about the natural habitats of these species.


Asunto(s)
Escherichia/clasificación , Microbiología del Agua , Animales , Escherichia/genética , Escherichia/aislamiento & purificación , Escherichia/patogenicidad , Escherichia coli/genética , Genes Bacterianos , Humanos , Filogenia , Reacción en Cadena de la Polimerasa
6.
B-ENT ; 10(4): 303-7, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25654955

RESUMEN

BACKGROUND: Carcinoid tumours are rare, particularly in the head and neck region. When occurring in this area, they mainly affect the larynx. The first case of primary well-differentiated carcinoid tumour arising from the nasopharynx was documented in 2009 and treated by combined external beam radiation and cold somatostatin analogue with a fatal outcome. To our knowledge, no case of this type of lesion has been successfully treated with surgery and radiotherapy until now. OBJECTIVE: To make physicians aware that typical carcinoid nasopharyngeal tumour can be treated by surgery and adjuvant radiotherapy. METHOD: We report the management of a typical carcinoid nasopharyngeal tumour in a 68-year-old female successfully treated with endoscopic surgery and adjuvant radiotherapy. We also review the relevant literature. CONCLUSION: Patients with close margins at the time of the surgery may need adjuvant radiotherapy to prevent recurrence. After a negative octreotide scintigraphy, periodical follow-up only is sufficient.


Asunto(s)
Tumor Carcinoide/terapia , Endoscopía/métodos , Neoplasias Nasofaríngeas/terapia , Anciano , Tumor Carcinoide/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Neoplasias Nasofaríngeas/patología , Radioterapia Adyuvante
7.
Br J Sports Med ; 46(11): 770-9, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22685119

RESUMEN

Challenging environmental conditions, including heat and humidity, cold, and altitude, pose particular risks to the health of Olympic and other high-level athletes. As a further commitment to athlete safety, the International Olympic Committee (IOC) Medical Commission convened a panel of experts to review the scientific evidence base, reach consensus, and underscore practical safety guidelines and new research priorities regarding the unique environmental challenges Olympic and other international-level athletes face. For non-aquatic events, external thermal load is dependent on ambient temperature, humidity, wind speed and solar radiation, while clothing and protective gear can measurably increase thermal strain and prompt premature fatigue. In swimmers, body heat loss is the direct result of convection at a rate that is proportional to the effective water velocity around the swimmer and the temperature difference between the skin and the water. Other cold exposure and conditions, such as during Alpine skiing, biathlon and other sliding sports, facilitate body heat transfer to the environment, potentially leading to hypothermia and/or frostbite; although metabolic heat production during these activities usually increases well above the rate of body heat loss, and protective clothing and limited exposure time in certain events reduces these clinical risks as well. Most athletic events are held at altitudes that pose little to no health risks; and training exposures are typically brief and well-tolerated. While these and other environment-related threats to performance and safety can be lessened or averted by implementing a variety of individual and event preventative measures, more research and evidence-based guidelines and recommendations are needed. In the mean time, the IOC Medical Commission and International Sport Federations have implemented new guidelines and taken additional steps to mitigate risk even further.


Asunto(s)
Altitud , Regulación de la Temperatura Corporal/fisiología , Frío/efectos adversos , Calor/efectos adversos , Deportes , Aclimatación/fisiología , Mal de Altura/prevención & control , Rendimiento Atlético/fisiología , Clima Frío/efectos adversos , Deshidratación/prevención & control , Ejercicio Físico/fisiología , Congelación de Extremidades/prevención & control , Instituciones de Salud/provisión & distribución , Trastornos de Estrés por Calor/prevención & control , Humanos , Hipotermia/prevención & control , Trastornos Respiratorios/prevención & control , Factores de Riesgo
8.
Eur J Clin Microbiol Infect Dis ; 30(3): 343-54, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20967479

RESUMEN

Staphylococcal species, notably, coagulase-negative staphylococci (CoNS), are frequently misidentified using phenotypic methods. The partial nucleotide sequences of the tuf and gap genes were determined in 47 reference strains to assess their suitability, practicability, and discriminatory power as target molecules for staphylococcal identification. The partial tuf gene sequence was selected and further assessed with a collection of 186 strains, including 35 species and subspecies. Then, to evaluate the efficacy of this genotyping method versus the technology of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), the 186 strains were identified using MALDI-TOF-MS (Axima® Shimadzu) coupled to the SARAMIS® database (AnagnosTec). The French National Reference Center for Staphylococci identification method was used as a reference. One hundred and eighty-four strains (98.9%) were correctly identified by tuf gene sequencing. Only one strain was misidentified and one was unidentified. MALDI-TOF-MS identified correctly 138 isolates (74.2%). Four strains were misidentified, 39 were unidentified, five were identified at the group (hominis/warneri) level, and one strain was identified at the genus level. These results confirm the value of MALDI-TOF-MS identification for common species in clinical laboratory practice and the value of the partial tuf gene sequence for the identification of all staphylococcal species as required in a reference laboratory.


Asunto(s)
Proteínas Bacterianas/genética , Técnicas Bacteriológicas , ADN Bacteriano/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Staphylococcus/clasificación , Staphylococcus/genética , Proteínas Bacterianas/análisis , Coagulasa/metabolismo , ADN Bacteriano/genética , Genes Bacterianos , Genotipo , Fenotipo , Análisis de Secuencia de ADN , Staphylococcus/aislamiento & purificación
10.
Eur J Med Genet ; 64(5): 104193, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33746037

RESUMEN

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder of motile cilia. With few exceptions, PCD is an autosomal recessive condition, and there are over 40 genes associated with the condition. We present a case of a newborn female with clinical features of PCD, specifically the Kartagener syndrome phenotype, due to variants in TTC25. This gene has been previously associated with PCD in three families. Two multi-gene panels performed as a neonate and at two years of age were uninformative. Exome sequencing was performed by the Care4Rare Canada Consortium on a research basis, and an apparent homozygous intronic variant (TTC25:c.1145+1G > A) was identified that was predicted to abolish the canonical splice donor activity of exon 8. The child's mother was a heterozygous carrier of the variant. The paternal sample did not show the splice variant, and homozygosity was observed across the paternal locus. Microarray analysis showed a 50 kb heterozygous deletion spanning the genes TTC25 and CNP. This is the first example of a pathogenic gross deletion in trans with a splice variant, resulting in TTC25-related PCD.


Asunto(s)
Proteínas Portadoras/genética , Eliminación de Gen , Síndrome de Kartagener/genética , Proteínas Portadoras/metabolismo , Variaciones en el Número de Copia de ADN , Femenino , Humanos , Recién Nacido , Síndrome de Kartagener/patología , Sitios de Empalme de ARN
13.
Cytogenet Genome Res ; 125(3): 176-85, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19738378

RESUMEN

Human telomeres play a major role in stabilizing chromosome ends and preventing fusions. Chromosomes bearing a broken end are rescued by the acquisition of a new telomeric cap without any subtelomeric sequences being present at the breakpoint, a process referred to as chromosome healing. Conversely, a loss of telomeric function or integrity can lead to the presence of interstitial telomeres at the junction site in translocations or ring chromosomes. In order to determine the frequency at which interstitial telomeres or chromosome healing events are observed in target chromosome abnormalities, we conducted a retrospective FISH study using pan-telomeric and chromosome-specific subtelomeric probes on archival material from 40 cases of terminal deletions, translocations or ring chromosomes. Of the 19 terminal deletions investigated, 17 were negative for the subtelomeric probe specific to the deleted arm despite being positive for the pan-telomeric probe. These 17 cases were thus considered as having been rescued through chromosome healing, suggesting that this process is frequent in terminal deletions. In addition, as 2 of these cases were inherited from a parent bearing the same deletion, chromosomes healed by this process are thus stable through mitosis and meiosis. Regarding the 13 cases of translocations and 8 ring chromosomes, 4 and 2 cases respectively demonstrated pan-telomeric sequences at the interstitial junction point. Furthermore, 2 cases of translocations and 1 ring chromosome had both interstitial pan-telomeres and subtelomeres, whereas 2 other cases of ring chromosomes and 1 case of translocation only showed interstitial subtelomeres. Therefore, interstitial (sub)telomeric sequences in translocations and ring chromosomes are more common than previously thought, as we found a frequency of 43% in this study. Moreover, our results illustrate the necessity of performing FISH with both subtelomeric and pan-telomeric probes when investigating these rearrangements, as the breakpoints can be either in the distal part of the pan-telomeres, or in between the 2 types of sequences.


Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos , Telómero , Inestabilidad Cromosómica , Deleción Cromosómica , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Estudios Retrospectivos , Cromosomas en Anillo , Translocación Genética
14.
Mol Ecol ; 18(21): 4422-33, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19804376

RESUMEN

The basidiomycetous fungus Onnia tomentosa is one of the most widespread root rot pathogens in North America. Although the disease is more severe on spruce and pine trees, this pathogen can infect several coniferous species. To study the population structure of O. tomentosa, we harvested 180 basidiocarps in a 45-year-old white spruce plantation in western Quebec in autumn 1997 and extracted DNA directly from individual basidiocarps. Using a combination of spatial coordinates and molecular data based on the analysis of two mitochondrial and three nuclear loci, we measured the average genet size and molecular diversity and assessed the relative contribution of basidiospores and vegetative growth to the stand colonization. Most of the sampled basidiocarps that clustered spatially belonged to the same genet. A total of 37 discrete multilocus genets of an average size of 3.42 m were obtained. The genet size distribution was skewed towards smaller genets (<3 m) that displayed higher diversity than the larger genets (>3 m). The nuclear loci were in Hardy-Weinberg equilibrium in the larger genets, but not in the smaller genets, which displayed a deficiency of heterozygotes. This suggests a Wahlund effect, whereby different colonization events resulted in expected heterozygosity higher than observed heterozygosity. Using an estimate of the growth rate of the fungus, only a few of the largest genets were approximately the age of the plantation. These observations are consistent with the colonization by basidiospores subsequent to site preparation and tree planting followed by secondary colonization events and vegetative spread.


Asunto(s)
Basidiomycota/genética , Genética de Población , Picea/microbiología , Alelos , Basidiomycota/crecimiento & desarrollo , Núcleo Celular/genética , ADN de Hongos/genética , ADN Mitocondrial/genética , Frecuencia de los Genes , Marcadores Genéticos , Enfermedades de las Plantas/microbiología , Polimorfismo Conformacional Retorcido-Simple , Quebec , Análisis de Secuencia de ADN , Árboles/microbiología
16.
Cell Mol Biol (Noisy-le-grand) ; 55(2): 46-54, 2009 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-19656451

RESUMEN

Most rodent models of porphyria cutanea tarda (PCT) share in common the administration of iron and agents that induce transcription of cytochrome P450s. Dissection of changes related to porphyrin accumulation required generation of a genetic model free from exogenous precipitants. Mice heterozygous for a null Urod mutation and homozygous for null Hfe alleles spontaneously develop major increases in hepatic and urinary porphyrins several months after weaning but the high % uroporphyrin signature of PCT is established earlier, before total hepatic and urinary porphyrins rise. Total porphyrin levels eventually plateau at higher levels in females than in males. Porphyrinogens were the dominant tetrapyrroles accumulating in hepatocytes. Hepatic Urod activity is markedly reduced but total hepatic heme content does not diminish. Microsomal heme, however, is reduced and in vitro metabolism of prototype substrates showed that some but not all cytochrome P450 activities are reduced. High hepatic levels of uroporphyrinogen are also associated with increased glutathione S-transferase activity and elevated mRNA of 2 transporters, Abcc1 and Abcc4. This murine model of familial PCT affords the opportunity to study changes in porphyrinogen and porphyrin accumulation and transport in the absence of exogenous factors that alter P450 activity and transmembrane transporters.


Asunto(s)
Porfiria Cutánea Tardía/genética , Animales , Sistema Enzimático del Citocromo P-450/metabolismo , Modelos Animales de Enfermedad , Femenino , Genotipo , Glutatión Transferasa/metabolismo , Hemo/análisis , Proteína de la Hemocromatosis , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/metabolismo , Hígado/metabolismo , Estudios Longitudinales , Masculino , Proteínas de la Membrana/deficiencia , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/antagonistas & inhibidores , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Porfiria Cutánea Tardía/patología , Porfirinas/sangre , Porfirinas/orina , Uroporfirinógeno Descarboxilasa/deficiencia , Uroporfirinógeno Descarboxilasa/genética , Uroporfirinógeno Descarboxilasa/metabolismo , Uroporfirinógenos/metabolismo
17.
Parasite Immunol ; 30(5): 280-92, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18312504

RESUMEN

Proteasomes are the main producers of Ag loaded onto MHC class I molecules. Following IFN-gamma stimulation however, the constitutive subunits of the proteasome are replaced by the immunosubunits low molecular weight protein 2 (LMP2), multicatalytic endopeptidase complex-like 1 and low molecular weight protein 7 (LMP7), which generally heighten the immunogenecity of proteasome generated epitopes. Given that Trypanosoma cruzi, the aetiological agent of Chagas' disease, elicits a T(helper)1 response from its host if the infection is to be contained, the aim of this study was to verify whether this parasite modulates J774 and B10R mouse macrophage (MuPhi) immunoproteasome subunit and MHC class I expressions and, if so, identify the mechanism(s) responsible for that modulation. Results show that T. cruzi infection of mouse MuPhi reduces IFN-gamma-mediated immunoproteasome synthesis, along with MHC class I mRNA synthesis and cell surface expression. The infection by T. cruzi induces the release of reactive oxygen species (ROS) from MuPhi, and those ROS significantly inhibit protein tyrosine phosphatase activity, thereby leading to the activation of the SAPK/JNK signalling pathway, which is responsible for the observed IFN-gamma-mediated immunoproteasome synthesis and MHC class I down-regulation. To our knowledge, this is the first report that specifically identifies a mechanism by which a pathogen achieves immunoproteasome down-modulation.


Asunto(s)
Enfermedad de Chagas/enzimología , Enfermedad de Chagas/inmunología , Interferón gamma/inmunología , Macrófagos/inmunología , Macrófagos/parasitología , Complejo de la Endopetidasa Proteasomal/metabolismo , Trypanosoma cruzi/inmunología , Animales , Presentación de Antígeno , Enfermedad de Chagas/parasitología , Cisteína Endopeptidasas/inmunología , Regulación hacia Abajo , Antígenos de Histocompatibilidad Clase I/biosíntesis , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , MAP Quinasa Quinasa 4/inmunología , Macrófagos/enzimología , Ratones , Complejos Multienzimáticos/inmunología , Células 3T3 NIH , Complejo de la Endopetidasa Proteasomal/biosíntesis , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/inmunología , Proteínas Tirosina Fosfatasas/antagonistas & inhibidores , Proteínas Tirosina Fosfatasas/inmunología , Proteínas Tirosina Fosfatasas/metabolismo , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Especies Reactivas de Oxígeno/inmunología
18.
J Inherit Metab Dis ; 31(2): 178-87, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18415698

RESUMEN

In the late 1990s, the identification of transporters and transporter-associated genes progressed substantially due to the development of new cloning approaches such as expression cloning and, subsequently, to the implementation of the human genome project. Since then, the role of many transporter genes in human diseases has been elucidated. In this overview, we focus on inherited disorders of epithelial transporters. In particular, we review genetic defects of the genes encoding glucose transporters (SLC2 and SLC5 families) and amino acid transporters (SLC1, SLC3, SLC6 and SLC7 families).


Asunto(s)
Trastornos Innatos del Transporte de Aminoácidos/genética , Sistemas de Transporte de Aminoácidos/genética , Errores Innatos del Metabolismo de los Carbohidratos/genética , Células Epiteliales/metabolismo , Proteínas de Transporte de Monosacáridos/genética , Trastornos Innatos del Transporte de Aminoácidos/metabolismo , Sistemas de Transporte de Aminoácidos/metabolismo , Aminoácidos/metabolismo , Animales , Errores Innatos del Metabolismo de los Carbohidratos/metabolismo , Predisposición Genética a la Enfermedad , Glucosa/metabolismo , Humanos , Proteínas de Transporte de Monosacáridos/metabolismo , Fenotipo , Proteínas de Transporte de Sodio-Glucosa/genética , Proteínas de Transporte de Sodio-Glucosa/metabolismo
19.
J Appl Microbiol ; 104(5): 1525-37, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18179542

RESUMEN

AIMS: The development and evaluation of a sensitive and specific TaqMan real-time polymerase chain reaction (PCR) for the detection and identification of Pantoea stewartii on maize. METHODS AND RESULTS: A TaqMan-based real-time PCR assay targeting the cpsD gene enabling specific detection of P. stewartii in maize leaves and seeds was developed. Under optimal conditions, the selected primers and probe were specific for the detection of all 14 reference P. stewartii strains by real-time PCR. The 32 non-Panteoa and eight other Pantoea strains tested negative. The TaqMan PCR assay detected 1 pg of purified DNA and 10(4)P. stewartii colony forming units per millilitre (10 cells per reaction) in pure cultures consisting of 92.0% intact (viable) cells. Direct processing of leaf lesions and seeds by the real-time PCR detected 10 and 50 P. stewartii cells per reaction respectively. TaqMan real-time PCR results were validated by dilution plating of macerates and PCR-based subcloning followed by DNA sequencing. CONCLUSIONS: The real-time PCR assay described is a rapid, reliable and more sensitive tool for the detection of P. stewartii. SIGNIFICANCE AND IMPACT OF THE STUDY: This real-time PCR assay would avoid false-negative results and reduce the time required for certifying maize seed shipments.


Asunto(s)
Microbiología de Alimentos , Pantoea/aislamiento & purificación , Enfermedades de las Plantas/microbiología , Zea mays/microbiología , Proteínas Bacterianas/genética , Secuencia de Bases , Cartilla de ADN/genética , ADN Bacteriano/análisis , Galactosiltransferasas/genética , Viabilidad Microbiana , Datos de Secuencia Molecular , Pantoea/genética , Filogenia , Hojas de la Planta/microbiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Semillas/microbiología
20.
Plant Dis ; 92(7): 1138, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30769510

RESUMEN

Amylostereum areolatum (Fr.) Boidin (Russulales: Stereaceae) is a white rot fungus that has a symbiotic relationship with several woodwasps including Sirex noctilio Fabricius (Hymenoptera: Siricidae). The vectored fungus together with a phytotoxic mucus, both injected during oviposition by the female S. noctilio, rapidly weaken the host tree, rendering it susceptible to larval development (3). Host trees of A. areolatum include species of Pinus (mainly), Abies, Larix, and Picea and Cryptomeria japonica and Pseudotsuga menziesii (Fungal Databases [online]; USDA). The siricid woodwasp is native to Eurasia and North Africa and has been introduced into New Zealand, Australia, South America, and South Africa (1). In July of 2005, the first established North American population of S. noctilio was reported in Oswego, NY. Prompted by this initial discovery, a trap survey of Ontario counties located along the Canada-U.S. border, close to Upstate New York, was conducted in September and October of 2005. S. noctilio females were captured in four locations in southern Ontario. Two additional locations for S. noctilio were also reported in a survey conducted independently (2). In September and October of 2006, logs of Scots pines showing current Sirex oviposition sites were harvested from the Ontario area bordered by Lakes Huron, Erie, and Ontario to determine the presence of the species-specific fungal symbiont of S. noctilio, A. areolatum. Fungal isolates were obtained by surface sterilizing wood chips showing decay columns followed by incubation at 20°C on 2% malt extract agar. Cultures with morphological characteristics typical of A. areolatum-presence of clamp connections and arthrospores-were used for DNA analysis to confirm species identification. DNA sequences of the internal transcribed spacer (ITS) of the ribosomal RNA gene were queried against the NCBI GenBank database. There was a 99 to 100% match between the ITS sequences from the Ontario isolates and sequences from European and Asian A. areolatum isolates (GenBank Accession Nos. EU249343 and EU249344 versus AF454428, AF506405, AY781245, and AF218389). Matches with A. chailletii (Pers.) Boidin, a native related species, were around 97%. These results confirmed the presence of A. areolatum in the infested material. Cultures were deposited in the National Mycological Herbarium of Canada (DAOM 239280-DAOM 239295). To our knowledge, this represents the first report of A. areolatum in Canada. In its natural range, the insect-fungal complex exists in equilibrium with its host trees and parasites, thus, few negative impacts are observed. However, in the Southern Hemisphere where it has been introduced, it has become a major pest, attacking many important commercial North American species planted as exotics (1). Conifer forests in Canada are threatened by the spread of the S. noctilio/A. areolatum complex, particularly plantations and stands of Pinus banksiana, P. contorta, P. ponderosa, P. resinosa, P. strobus, and P. sylvestris. A survey of Eastern Canada to detect the presence of S. noctilio is on going, and genetics work is being conducted to determine the origin of the introduction of A. areolatum. References: (1) W. M. Ciesla. J. For. 101:18, 2003. (2) P. de Groot et al. Gt. Lakes Entomol. 39:49, 2006. (3) B. Slippers et al. S. Afr. J. Sci. 99:70, 2003.

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