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BACKGROUND: Microbiome/host interactions describe characteristics that affect the host's health. Shotgun metagenomics includes sequencing a random subset of the microbiome to analyze its taxonomic and metabolic potential. Reconstruction of DNA fragments into genomes from metagenomes (called metagenome-assembled genomes) assigns unknown fragments to taxa/function and facilitates discovery of novel organisms. Genome reconstruction incorporates sequence assembly and sorting of assembled sequences into bins, characteristic of a genome. However, the microbial community composition, including taxonomic and phylogenetic diversity may influence genome reconstruction. We determine the optimal reconstruction method for four microbiome projects that had variable sequencing platforms (IonTorrent and Illumina), diversity (high or low), and environment (coral reefs and kelp forests), using a set of parameters to select for optimal assembly and binning tools. METHODS: We tested the effects of the assembly and binning processes on population genome reconstruction using 105 marine metagenomes from 4 projects. Reconstructed genomes were obtained from each project using 3 assemblers (IDBA, MetaVelvet, and SPAdes) and 2 binning tools (GroopM and MetaBat). We assessed the efficiency of assemblers using statistics that including contig continuity and contig chimerism and the effectiveness of binning tools using genome completeness and taxonomic identification. RESULTS: We concluded that SPAdes, assembled more contigs (143,718 ± 124 contigs) of longer length (N50 = 1632 ± 108 bp), and incorporated the most sequences (sequences-assembled = 19.65%). The microbial richness and evenness were maintained across the assembly, suggesting low contig chimeras. SPAdes assembly was responsive to the biological and technological variations within the project, compared with other assemblers. Among binning tools, we conclude that MetaBat produced bins with less variation in GC content (average standard deviation: 1.49), low species richness (4.91 ± 0.66), and higher genome completeness (40.92 ± 1.75) across all projects. MetaBat extracted 115 bins from the 4 projects of which 66 bins were identified as reconstructed metagenome-assembled genomes with sequences belonging to a specific genus. We identified 13 novel genomes, some of which were 100% complete, but show low similarity to genomes within databases. CONCLUSIONS: In conclusion, we present a set of biologically relevant parameters for evaluation to select for optimal assembly and binning tools. For the tools we tested, SPAdes assembler and MetaBat binning tools reconstructed quality metagenome-assembled genomes for the four projects. We also conclude that metagenomes from microbial communities that have high coverage of phylogenetically distinct, and low taxonomic diversity results in highest quality metagenome-assembled genomes.
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Genoma Microbiano , Metagenoma , Análisis de Secuencia de ADN/métodos , Algoritmos , Filogenia , Análisis de Secuencia de ADN/normas , Programas InformáticosRESUMEN
As coral reef habitats decline worldwide, some reefs are transitioning from coral- to algal-dominated benthos with the exact cause for this shift remaining elusive. Increases in the abundance of microbes in the water column has been correlated with an increase in coral disease and reduction in coral cover. Here we investigated how multiple reef organisms influence microbial communities in the surrounding water column. Our study consisted of a field assessment of microbial communities above replicate patches dominated by a single macro-organism. Metagenomes were constructed from 20 L of water above distinct macro-organisms, including (1) the coral Mussismilia braziliensis, (2) fleshy macroalgae (Stypopodium, Dictota and Canistrocarpus), (3) turf algae, and (4) the zoanthid Palythoa caribaeorum and were compared to the water microbes collected 3 m above the reef. Microbial genera and functional potential were annotated using MG-RAST and showed that the dominant benthic macro-organisms influence the taxa and functions of microbes in the water column surrounding them, developing a specific "aura-biome". The coral aura-biome reflected the open water column, and was associated with Synechococcus and functions suggesting oligotrophic growth, while the fleshy macroalgae aura-biome was associated with Ruegeria, Pseudomonas, and microbial functions suggesting low oxygen conditions. The turf algae aura-biome was associated with Vibrio, Flavobacterium, and functions suggesting pathogenic activity, while zoanthids were associated with Alteromonas and functions suggesting a stressful environment. Because each benthic organism has a distinct aura-biome, a change in benthic cover will change the microbial community of the water, which may lead to either the stimulation or suppression of the recruitment of benthic organisms.
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Microbial viruses can control host abundances via density-dependent lytic predator-prey dynamics. Less clear is how temperate viruses, which coexist and replicate with their host, influence microbial communities. Here we show that virus-like particles are relatively less abundant at high host densities. This suggests suppressed lysis where established models predict lytic dynamics are favoured. Meta-analysis of published viral and microbial densities showed that this trend was widespread in diverse ecosystems ranging from soil to freshwater to human lungs. Experimental manipulations showed viral densities more consistent with temperate than lytic life cycles at increasing microbial abundance. An analysis of 24 coral reef viromes showed a relative increase in the abundance of hallmark genes encoded by temperate viruses with increased microbial abundance. Based on these four lines of evidence, we propose the Piggyback-the-Winner model wherein temperate dynamics become increasingly important in ecosystems with high microbial densities; thus 'more microbes, fewer viruses'.
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Antozoos/virología , Ecosistema , Interacciones Huésped-Patógeno , Virus/patogenicidad , Animales , Antozoos/fisiología , Bacteriófagos/patogenicidad , Bacteriófagos/fisiología , Arrecifes de Coral , Genes Virales/genética , Lisogenia , Modelos Biológicos , Virulencia/genética , Virus/genética , Virus/aislamiento & purificaciónRESUMEN
Patients with leukemia relapsing after allogeneic hematopoietic SCT have a dismal prognosis. A second SCT offers a further opportunity for cure, but has a high rate of treatment failure. To determine the utility of this option, we analyzed 59 consecutive patients relapsing after a myeloablative HLA-matched sibling T cell-depleted (TCD) SCT. Twenty-five patients (13 relapsing within 6 months and 12 relapsing between 6 and 170 months after the first SCT) received a T-replete second SCT. Thirty-eight patients relapsing early had a shorter survival than the 21 patients relapsing later (median 96 vs 298 days, P=0.0002). In patients relapsing early, the second SCT did not improve OS compared with patients receiving non-SCT treatments (median survival 109 vs 80 days, P=0.41). In patients relapsing late, despite an early trend in favor of second SCT, survival was comparable for patients receiving a second SCT compared with non retransplanted patients (median survival 363.5 vs 162 days, P=0.49). Disappointingly, our results do not demonstrate an important survival benefit for a second T-replete allogeneic SCT to treat relapse following a TCD SCT.
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Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/inmunología , Leucemia/terapia , Linfocitos T/inmunología , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Estudios de Cohortes , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Células Madre Hematopoyéticas/citología , Humanos , Leucemia/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Reoperación , Tasa de Supervivencia , Linfocitos T/citología , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Homólogo , Adulto JovenRESUMEN
Oxygen minimum zones (OMZs) are oceanographic features that affect ocean productivity and biodiversity, and contribute to ocean nitrogen loss and greenhouse gas emissions. Here we describe the viral communities associated with the Eastern Tropical South Pacific (ETSP) OMZ off Iquique, Chile for the first time through abundance estimates and viral metagenomic analysis. The viral-to-microbial ratio (VMR) in the ETSP OMZ fluctuated in the oxycline and declined in the anoxic core to below one on several occasions. The number of viral genotypes (unique genomes as defined by sequence assembly) ranged from 2040 at the surface to 98 in the oxycline, which is the lowest viral diversity recorded to date in the ocean. Within the ETSP OMZ viromes, only 4.95% of genotypes were shared between surface and anoxic core viromes using reciprocal BLASTn sequence comparison. ETSP virome comparison with surface marine viromes (Sargasso Sea, Gulf of Mexico, Kingman Reef, Chesapeake Bay) revealed a dissimilarity of ETSP OMZ viruses to those from other oceanic regions. From the 1.4 million non-redundant DNA sequences sampled within the altered oxygen conditions of the ETSP OMZ, more than 97.8% were novel. Of the average 3.2% of sequences that showed similarity to the SEED non-redundant database, phage sequences dominated the surface viromes, eukaryotic virus sequences dominated the oxycline viromes, and phage sequences dominated the anoxic core viromes. The viral community of the ETSP OMZ was characterized by fluctuations in abundance, taxa and diversity across the oxygen gradient. The ecological significance of these changes was difficult to predict; however, it appears that the reduction in oxygen coincides with an increased shedding of eukaryotic viruses in the oxycline, and a shift to unique viral genotypes in the anoxic core.
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Biodiversidad , Oxígeno/metabolismo , Agua de Mar/virología , Fenómenos Fisiológicos de los Virus , Anaerobiosis , Bacterias/clasificación , Bacterias/genética , Bacteriófagos/genética , Bacteriófagos/fisiología , Chile , Genotipo , Nitrógeno/metabolismo , Océanos y Mares , Oxidación-Reducción , Filogenia , Azufre/metabolismo , Virus/genéticaRESUMEN
Nutrient transporters and ABC efflux pumps at the blood-brain barrier are major determinants of drug penetration into the brain. Immunohistochemical analysis of transporter subcellular localization is challenging due to the close apposition of the luminal and abluminal microvessel plasma membranes. We employed in vivo perfusion of biotinylation reagent through rat brain microvessels to domain-specifically label proteins exposed on the microvessel luminal surface. Using this approach, we analyzed the luminal/abluminal localization of a number of blood-brain barrier transporters identified by quantitative PCR profiling as being highly expressed and enriched in rat brain endothelial cells compared with whole brain. We also examined the apical/basal-lateral distribution of transporters in the choroid plexus, a secondary site for transport of nutrients between the blood and CNS. We detected P-glycoprotein (Pgp) (Abcb1), ATP-binding cassette (Abc) g2, multidrug resistance protein (Mrp) 4 (Abcc4), glucose transporter 1 (Glut1) (Slc2a1), Lat1 (Slc7a5), and monocarboxylate transporter-1 (Mct1) (Slc16a1) on the luminal surface of rat cerebral microvessels by both immunofluorescence staining and Western blotting of in vivo biotinylated proteins. Mrp1 (Abcc1) appeared primarily abluminal by immunofluorescence staining, and was barely detectable in the biotinylated protein fraction. Organic anion transporter (Oat) 3 (Slc22a8), organic anion transporter polypeptide (Oatp) 2b1 (Slco2b1, Oatpb), and Mrp5 (Abcc5) were not detected on the luminal surface using either method, while Oatp1a4 (Slco1a4, Oatp2) appeared to partially localize to the microvessel lumen by immunofluorescence staining, but was not detected in the biotinylated protein fraction by Western blotting. Lat1, Mrp1 and Mrp4 were detected on the basal-lateral surface of lateral ventricle choroid plexus epithelial cells. Mrp5, Oct3 and Oatp2b1 (Oatpb) were detected in the ependymal cells lining the ventricle. We did not detect Pgp expression in choroid plexus by immunofluorescence staining. In vivo biotinylation provides a method for domain-specific labeling of luminal surface proteins within the capillaries of the blood-brain barrier, allowing for biochemical analysis of protein localization and facilitating optical discrimination of the luminal and abluminal endothelial surfaces.
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Barrera Hematoencefálica/fisiología , Circulación Cerebrovascular/fisiología , Plexo Coroideo/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Biotinilación , Barrera Hematoencefálica/ultraestructura , Western Blotting , Línea Celular , Plexo Coroideo/irrigación sanguínea , Plexo Coroideo/ultraestructura , Epéndimo/irrigación sanguínea , Epéndimo/metabolismo , Epéndimo/ultraestructura , Perfilación de la Expresión Génica , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 1/metabolismo , Humanos , Riñón/citología , Transportador de Aminoácidos Neutros Grandes 1/genética , Transportador de Aminoácidos Neutros Grandes 1/metabolismo , Masculino , Proteínas de Transporte de Membrana/genética , Microcirculación/fisiología , Microcirculación/ultraestructura , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Ratas , Ratas Sprague-Dawley , Simportadores/genética , Simportadores/metabolismo , TransfecciónRESUMEN
Additional evidence for the rare kaon decay K+-->pi+nu(nu) has been found in a new data set with comparable sensitivity to the previously reported result. One new event was observed in the pion momentum region examined, 211
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OBJECTIVE: Our purpose was to determine the factors involved in the cancer screening decisions of family physicians in situations where the clinical practice guidelines are unclear or conflicting as opposed to when they are clear and uncontroversial. STUDY DESIGN: We analyzed discussions with focus groups using a constant comparative approach. POPULATION: A total of 73 family physicians in active practice participated in 10 focus groups (1 urban group and 1 rural group in each of 5 Canadian provinces). OUTCOME MEASURES: Our main outcome measures were participants' perceptions regarding cancer screening when the guidelines were unclear or conflicting. RESULTS: We propose a model of the determinants of cancer screening decision making with regard to unclear and conflicting guidelines. This model is rooted in the physician-patient relationship, and is an interactive process influenced by patient factors (anxiety, expectations, and family history) and physician factors (perception of guidelines, clinical practice experience, influence of colleagues, distinction between the screening styles of specialists and family physicians, and the amount of time and financial costs involved in performing the maneuver). CONCLUSIONS: Our model is unique, because it is embedded in the physician-patient relationship. Ultimately, a modified model could be used to design interventions to assist with the implementation of preventive services guidelines.
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Toma de Decisiones , Medicina Familiar y Comunitaria/normas , Adhesión a Directriz/estadística & datos numéricos , Tamizaje Masivo/normas , Neoplasias/diagnóstico , Selección de Paciente , Guías de Práctica Clínica como Asunto/normas , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adulto , Actitud del Personal de Salud , Canadá , Comunicación , Técnicas de Apoyo para la Decisión , Medicina Familiar y Comunitaria/métodos , Medicina Familiar y Comunitaria/estadística & datos numéricos , Femenino , Grupos Focales , Conocimientos, Actitudes y Práctica en Salud , Investigación sobre Servicios de Salud , Humanos , Masculino , Persona de Mediana Edad , Modelos Psicológicos , Relaciones Médico-Paciente , Ubicación de la Práctica Profesional/estadística & datos numéricosRESUMEN
BACKGROUND: Physician mammography referral remains below optimal levels despite a long-standing recommendation that all women ages 50 to 69 years receive screening mammography every 1 to 2 years. The purpose of this study was to determine physician and practice environment predictors of family physicians' screening mammography referral rates to women ages 50-69 years. METHOD: A cohort of 498 recently-licensed family physicians was followed for 18-months of incipient medical practice. The referral rate was the percentage of new clinically eligible women patients seen in a primary care context who had a screening mammogram ordered by the study physician. Mammograms and independent variables were identified from physician claims to a Canadian universal health insurance agency. The effects of factors in a conceptual framework were assessed using multivariable linear regression. RESULTS: Correlates of higher mammography referral rates were female gender, better general prevention knowledge, the combination of comprehensive inquiry and continuity care, lower patient volume, and lower shared primary care (multivariable model R(2) = 0.47). Factors belonging to practice environment explained more of the observed variance than did physician characteristics. CONCLUSIONS: Mammography referral varies enormously and almost half of the variance is explained by physician characteristics and practice preferences. Higher mammography referral is observed in practices with more comprehensive and continuity care.
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Medicina Familiar y Comunitaria/estadística & datos numéricos , Adhesión a Directriz , Mamografía/estadística & datos numéricos , Pautas de la Práctica en Medicina , Derivación y Consulta , Adulto , Anciano , Actitud del Personal de Salud , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , QuebecRESUMEN
Thymidine phosphorylase/platelet-derived endothelial cell growth factor (TPase/PD-ECGF) is a catabolic enzyme that has been shown to be chemotactic for endothelial cells in vitro and angiogenic in vivo. TPase/PD-ECGF expression is increased in a variety of tumors. In the skin, TPase is active in normal keratinocytes in vitro and in vivo. Our objective was to study the expression and localization of TPase/PD-ECGF by immunohistochemical analysis in normal skin and cutaneous tumors and to correlate this information with enzymatic activity of TPase. TPase/PD-ECGF expression was observed in keratinocytes with intense staining of the infundibulum of hair follicles but no staining of hair bulbs. Expression localized primarily to the nucleus of keratinocytes in the basal layer but was more intense and cytoplasrmic in suprabasal keratinocytes. Increased expression of TPase/PD-ECGF in differentiated cells was confirmed by in vitro studies of TPase activity. In cutaneous tumors, there was positive staining for TPase/ PD-ECGF in squamous cell carcinomas (10/10), eccrine poromas (3/4), eccrine syringomas (4/4), trichoepitheliomas (1/3), and tumors of the follicular infundibulum (2/3) and melanomas (5/8). There was no staining of any intradermal nevi (0/2), basal cell carcinomas (0/10) or Merkel cell carcinoma (0/1). We conclude TPase/PD-ECGF is found throughout the epidermis and its expression increases with differentiation of keratinocytes. In cutaneous tumors, expression of TPase/PD-ECGF may be linked to the cell of origin of the tumor as well as the tumor's degree of differentiation.
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Neoplasias Cutáneas/enzimología , Piel/enzimología , Timidina Fosforilasa/metabolismo , Especificidad de Anticuerpos , Tamaño de la Célula , Folículo Piloso/citología , Folículo Piloso/enzimología , Humanos , Técnicas para Inmunoenzimas , Queratinocitos/citología , Queratinocitos/enzimología , Piel/patología , Neoplasias Cutáneas/patología , Células Tumorales CultivadasRESUMEN
Several members of the CD44 family of hyaluronan receptors are expressed on keratinocytes. To identify factors that might be important in regulating CD44 expression, we studied CD44 expression on keratinocytes growing in vitro under a variety of conditions and on cells isolated directly from epidermis. Using Western immunoblots and metabolic labeling, we showed that the pattern of CD44 proteins expressed by keratinocytes was strongly influenced by growth and differentiation. Many protein forms of CD44 are expressed on proliferating keratinocytes in preconfluent cultures, whereas only a few forms are expressed on differentiated cells and in confluent cultures. In preconfluent monolayers, at least four splice variants were identified, including epican, CD44H, CD44E, and a 180-kDa variant. In differentiated cells or in confluent cultures, by contrast, only epican and the 180-kDa protein variant were found. Synthesis of all variants is strongly downregulated when keratinocytes become confluent or when they differentiate. Epican is the predominant form of CD44 on keratinocytes under all conditions and is expressed as a heparan, chondroitin, or keratan sulfate proteoglycan. Preconfluent basal keratinocytes, but not confluent or differentiated keratinocytes, also express chondroitin sulfate proteoglycan forms of CD44E and of the 180-kDa core protein. The modal size of the epican expressed on differentiated keratinocytes is smaller than the size of the epican expressed on basal keratinocytes. Thus, cell confluence and differentiation regulate several aspects of CD44 expression on keratinocytes, suggesting nuances in function for the different protein forms.
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Receptores de Hialuranos/biosíntesis , Queratinocitos/citología , Queratinocitos/inmunología , Proteoglicanos/biosíntesis , Diferenciación Celular , División Celular , Células Cultivadas , Células Epidérmicas , Epidermis/inmunología , HumanosRESUMEN
Comparing 36 disruptive behavior-disordered and 40 normal female adolescents, we found higher levels of anxiety and poorer performance on a measure of verbal fluency in the clinical sample. No group differences were found on a nonverbal measure of reflectivity nor on a measure of interpersonal cognitive problem solving. Nor was evidence found for an hypothesized anxiety-related performance decrement among disruptive behavior-disordered youth. However, anxiety induction facilitated performance across groups on interpersonal cognitive problem solving.
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Conducta del Adolescente , Trastornos de Ansiedad/psicología , Déficit de la Atención y Trastornos de Conducta Disruptiva/psicología , Cognición , Adolescente , Niño , Femenino , Humanos , Solución de ProblemasRESUMEN
CONTEXT: Clinical competence is a determinant of the quality of care delivered, and may be associated with use of health care resources by primary care physicians. Clinical competence is assumed to be assessed by licensing examinations, yet there is a paucity of information on whether scores achieved predict subsequent practice. OBJECTIVE: To determine if licensing examination scores were associated with selected aspects of quality of care and resource use in initial primary care practice. DESIGN: Prospective cohort study of recently licensed family physicians, followed up for the first 18 months of practice. SETTING: The Quebec health care system. PARTICIPANTS: A total of 614 family physicians who passed the licensing examination between 1991 and 1993 and entered fee-for-service practice in Quebec. MAIN OUTCOME MEASURES: All patients seen by physicians were identified by the universal health insurance board and all health services provided to these patients were retrieved for the 18 months prior to (baseline) and after (follow-up) the physicians' entry into practice. Medical service and prescription claims files were used to measure rates of resource use (specialty consultation, symptom-relief prescribing compared with disease-specific prescribing) and quality of care (inappropriate prescribing, mammography screening). Baseline data were used to adjust for differences in practice population. RESULTS: Study physicians saw a total of 1116389 patients, of whom 113535 (10.2%) were elderly and 83391 (7.5%) were women aged 50 to 69 years. Physicians with higher licensing examination scores referred more of their patients for consultation (3.8/1000 patients per SD increase in score; 95% confidence interval [CI], 1.2-7.0; P = .005), prescribed to elderly patients fewer inappropriate medications (-2.7/1000 patients per SD increase in score; 95% CI, -4.8 to -0.7; P=.009) and more disease-specific medications relative to symptom-relief medications (3.9/1000 patients per SD increase in score; 95% CI, 0.3 to 7.4; P= .03), and referred more women aged 50 to 69 years (6.6/1000 patients per SD increase in score; 95% CI, 1.2-11.9; P = .02) for mammography screening. If patients of physicians with the lowest scores had experienced the same rates of consultation, prescribing, and screening as patients of physicians with the highest scores, an additional 3027 patients would have been referred, 179 fewer elderly patients would have been prescribed symptom-relief medication, 912 more elderly patients would have been prescribed disease-specific medication, 189 fewer patients would have received inappropriate medication, and 121 more women would have received mammography screening. CONCLUSIONS: Licensing examination scores are significant predictors of consultation, prescribing, and mammography screening rates in initial primary care practice.
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Competencia Clínica , Medicina Familiar y Comunitaria/normas , Recursos en Salud/estadística & datos numéricos , Licencia Médica , Pautas de la Práctica en Medicina/estadística & datos numéricos , Calidad de la Atención de Salud , Adulto , Anciano , Utilización de Medicamentos/estadística & datos numéricos , Evaluación Educacional , Medicina Familiar y Comunitaria/estadística & datos numéricos , Femenino , Política de Salud , Humanos , Modelos Lineales , Masculino , Mamografía/estadística & datos numéricos , Persona de Mediana Edad , Atención Primaria de Salud/normas , Estudios Prospectivos , Quebec , Derivación y Consulta/estadística & datos numéricos , Estados UnidosRESUMEN
beta-L-1,3-Dioxolane-cytidine (L-(-)-OddC) is a novel L-nucleoside, and its antitumor activity is under investigation in clinical trials. To evaluate the potential of L-(-)-OddC for treating hyperproliferative diseases of the skin, we examined its activity in human keratinocytes in vitro. The dose of L-(-)-OddC that inhibited the rate of proliferation of keratinocytes by 50% was 50 nM. L-(-)-OddC was about as cytotoxic as 9-beta-D-arabinofuranosylcytosine but was about 1,000 time more potent than 3'-azidothymidine. L-(-)-OddC caused irreversible growth arrest and induced differentiation of keratinocytes. L-(-)-OddC altered morphology, increased the cell size of keratinocytes and increased the expression of involucrin. These data suggest that L-(-)-OddC may have potential as a therapeutic agent against hyperproliferative skin diseases.
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Antimetabolitos Antineoplásicos/farmacología , Citosina/análogos & derivados , Dioxolanos/farmacología , Queratinocitos/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Tamaño de la Célula/efectos de los fármacos , Células Cultivadas , Citosina/farmacología , Humanos , Precursores de Proteínas/farmacología , Zidovudina/farmacologíaRESUMEN
We examined the prevalence of antimicrosomal and antithyroglobulin antibodies in psychiatric inpatients with unipolar depression (N = 218), bipolar disorder manic (N = 51), bipolar disorder depressed (N = 19), and bipolar disorder mixed (N = 26) in comparison with two control groups: psychiatric inpatients with adjustment disorder (N = 80) and family medicine outpatients without current psychiatric illness (N = 144). A statistical analysis that controlled for age and sex revealed the frequency of positive antibody titers not to be increased in patients with a diagnosis of unipolar depression (6.9%) or bipolar disorder manic (3.9%), when compared with patients with adjustment disorder (2.5%) and non-psychiatric subjects (6.9%). There was a weak trend toward an increased prevalence of antithyroid antibodies in patients with bipolar disorder, mixed (19%) or depressed subtype (16%). The excess occurrence of antibodies in patients with either mixed or depressed bipolar disorder did not appear to be related to lithium exposure, which was similar in all bipolar subgroups. When the intervening influences of age and sex are taken into account, unipolar depression does not appear to be associated with an excessive rate of antithyroid antibodies; however thyroid autoimmunity may be weakly associated with subtypes of bipolar disorder in which depressive symptoms are prominent.
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Anticuerpos/sangre , Trastorno Bipolar/inmunología , Trastorno Depresivo/inmunología , Glándula Tiroides/inmunología , Tiroiditis Autoinmune/complicaciones , Adulto , Distribución por Edad , Análisis de Varianza , Biomarcadores/sangre , Trastorno Bipolar/clasificación , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/fisiopatología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Estudios Transversales , Trastorno Depresivo/fisiopatología , Femenino , Humanos , Litio/inmunología , Litio/uso terapéutico , Masculino , Persona de Mediana Edad , Distribución por Sexo , Glándula Tiroides/fisiopatología , Tiroiditis Autoinmune/fisiopatología , Tirotropina/sangre , Tiroxina/sangreAsunto(s)
Confidencialidad/legislación & jurisprudencia , Registros Odontológicos/legislación & jurisprudencia , Relaciones Dentista-Paciente , Odontólogos/legislación & jurisprudencia , Humanos , Responsabilidad Legal , Mala Praxis/legislación & jurisprudencia , Massachusetts , Responsabilidad SocialRESUMEN
OBJECTIVE: To test whether individuals can be identified in a geographically defined population who would meet criteria for the eosinophilia-myalgia syndrome (EMS) established by the US Centers for Disease Control and Prevention (CDC), i.e, (1) eosinophil count > 1 x 10(9)/l, (2) myalgia severe enough to limit usual activities of daily living, and (3) no evidence of infection or neoplasm that could explain the first 2 findings. METHODS: To discover the number of individuals who would meet CDC criteria, the population was exhaustively searched using methods adapted from active pharmacoepidemiologic surveillance. Medical consultants and primary care practitioners were questioned as many as 5 times in a search for patients with severe myalgia. A predetermined protocol was used to screen those patients who appeared to meet CDC criteria for EMS using active surveillance methods. The study population was limited to Québec and Ontario (combined population 18,980,000) with special attention to the period July 1, 1992, to June 30, 1993. RESULTS: The prevalence of severe incapacitating myalgia was 43 per 100,000 persons, including 19 individuals with eosinophilia > 1 x 10(9)/l, who met CDC criteria for EMS. None of these individuals were reported to have taken L-tryptophan (LT). CONCLUSION: The CDC criteria for EMS are met by individuals in the general population who have never been exposed to LT.
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Centers for Disease Control and Prevention, U.S. , Síndrome de Eosinofilia-Mialgia/diagnóstico , Selección de Paciente , Adulto , Síndrome de Eosinofilia-Mialgia/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ontario , Prevalencia , Quebec , Triptófano/uso terapéutico , Estados UnidosRESUMEN
We examined CD44 expression on melanocytes to begin to understand what role CD44 might have in the normal behavior of melanocytes and to provide a basis for comparing CD44 expression in melanoma cells. CD44 was expressed on the entire surface of melanocytes and accentuated at the tips of dendritic processes. Two predominant forms of CD44 are expressed on cultured human foreskin melanocytes. One form has the covalent addition of chondroitin sulfate, whereas the other form has no chondroitin sulfate. Both use the hematopoietic, or CD44H, core protein. Using polymerase chain reaction primers that span the site where alternative splicing of CD44 occurs, we found only the cDNA coding CD44H. 12-O-Tetradecanoylphorbol 13-acetate increases the size of the chondroitin sulfate chain(s) attached to CD44 but not the proportion of CD44 molecules that carry chondroitin sulfate. Ninety percent of proteoglycans on melanocytes are chondroitin sulfate proteoglycans, and the CD44 chondroitin sulfate proteoglycan represented 10% of that total. These data show that CD44H is expressed as a "part-time" chondroitin sulfate proteoglycan on normal cultured melanocytes.
Asunto(s)
Epidermis/metabolismo , Receptores de Hialuranos/metabolismo , Melanocitos/metabolismo , Secuencia de Bases , Membrana Celular/metabolismo , Células Epidérmicas , Glicoproteínas/metabolismo , Humanos , Receptores de Hialuranos/química , Receptores de Hialuranos/genética , Isomerismo , Sondas Moleculares/genética , Datos de Secuencia Molecular , Proteoglicanos/química , Empalme del ARN , ARN Mensajero/genética , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
Eosinophilia myalgia syndrome (EMS), was defined by the Centers for Disease Control (CDC) as eosinophilia > 1000 mm3 and incapacitating myalgia without infection or neoplasm. Studies suggested that use of L-tryptophan (L-T), was a risk factor. We conducted a pharmacoepidemiological survey in Canada where access to L-T is limited. Using the active surveillance method, a 100% sample of potentially involved specialists and a 15% sample of family physicians from Ontario and Quebec were surveyed regarding treatment of patients with severe myalgia within the past year. Follow-up amplified clinical and laboratory information. Overall response rates were 61.4%. Thirty-eight per cent of respondents reported at least one patient. Of 6423 patients assessed, 19 'definite' and 25 'possible' EMS cases were identified. Information from physicians did not suggest use of L-T in patients with definite or possible EMS. It was considered that the cases found an underestimate of the incidence of EMS. Its continuing occurrence in Canada brings causal interpretations of earlier studies into question.