RESUMEN
Due to the decline of the Aral Sea fishery and recent efforts to expand the fisheries sector in Kazakhstan for both local consumption and global export, there is a need to sustain other fisheries in the area, including the Shardara Reservoir, which lies in the Syr Darya basin. Metals are present in the Syr Darya; yet, their impacts on fishery and consumer health remain unclear. Thus, the objectives of this study were to evaluate: 1) the potential impacts of metals on Syr Darya basin fish and 2) the human health risks posed by consumption of Shardara Reservoir fish. The health of the fishery was assessed by comparing surface water metal concentrations to maximum permissible concentrations (MPCs), calculating water quality index (WQI) and degree of contamination (Cd) values, and evaluating gene expression biomarker responses in wild-caught roach (Rutilus rutilus). To assess the risk to consumers, metal concentrations in roach were used to calculate hazard quotients (HQs) and hazard indices (HIs). Water concentrations of Cu, Fe, Mn, Se, Sr and V exceeded MPCs and all sites were classified as highly polluted based upon WQI and Cd values. This, along with site-specific differences in the expression of genes associated with xenobiotic metabolism and oxidative stress in roach, indicates potential risks to the fishery. Though all HQs and HIs were below 1 indicating a lack of significant risk to consumers, Pb levels in roach exceeded MPCs for safe consumption indicating a potential risk. Given the potential risks to the fishery and consumers, the development of pollution monitoring and management programs are warranted. The work presented here provides initial monitoring data that can be used to aid such efforts and also underscores the need to identify environmental stressors that may thwart the anticipated growth of fisheries in this region.
Asunto(s)
Cyprinidae , Metales Pesados , Contaminantes Químicos del Agua , Animales , Humanos , Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisis , Calidad del Agua , Metales , Metales Pesados/análisis , Medición de RiesgoRESUMEN
The Syr Darya is one of two major rivers in Central Asia supplying critical fresh water to the Aral Sea. In spite of the river's importance and agriculturally-intensive history, few studies have provided a modern evaluation of and the occurrence of pesticide residues potential effects to aquatic life. The primary goal of this investigation was to determine seasonal variations in ambient concentrations of modern and legacy pesticides in bottom sediment and water of the Syr Darya in Kazakhstan (KZ) downstream from an agriculturally-intensive watershed in Uzbekistan. Grab samples and passive samplers were used at five remote sampling stations during June 2015 to provide a baseline for ecotoxicological evaluation. Results were compared with samples collected during and after the agricultural growing season. Polar organic chemical integrative samplers (POCIS) were used in June and calibrated for time-weighted average concentrations of current use pesticides. Among legacy chlorinated pesticides measured in grab samples from the river, lindane (γ-HCH) was detected most frequently with the highest concentrations occurring during June. For all the sampling events, residues of lindane (γ-HCH) ranged from 0.014 to 0.24 µg/L detected in water samples, are among the highest concentrations reported for rivers globally. Concentrations of γ-HCH, p,p'-DDE and dieldrin were highest in October when dieldrin concentrations approached 0.4 µg/L. Sources of legacy pesticides may be either illicit upstream use or evidence of previous atmospheric contamination of glacial meltwater. Chronic exposure to these residues may lead to ecological risk to lower order organisms in both the sediment and water column.
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Hidrocarburos Clorados , Residuos de Plaguicidas , Plaguicidas , Contaminantes Químicos del Agua , Monitoreo del Ambiente , Hidrocarburos Clorados/análisis , Kazajstán , Plaguicidas/análisis , Medición de Riesgo , Estaciones del Año , Contaminantes Químicos del Agua/análisisRESUMEN
OBJECTIVE: This review was designed to identify highlights of the osteoarthritis (OA) genetics and epigenetics literature published between April 2017 and January 2018. DESIGN: A Pubmed literature search was conducted using the keywords 'osteoarthritis' and each of the following: 'genomic', 'genetic', 'epigenomic', 'epigenetic', 'histone', 'noncoding RNA', 'miRNA', 'lncRNA', 'DNA methylation', 'DNA hydroxymethylation', 'DNMT', and 'TET'. The dates of publication were restricted to 4/1/2017-1/15/2018. Results were compared to the same search terms limited to 4/1/2016-1/15/2017. RESULTS: Virtually all search term combinations demonstrated a decrease in papers published this year compared to last, with epigenetic and miRNA/lncRNA research being stable. Despite this, numerous advances were made this year, including the second large genome-wide association study (GWAS) study of hand OA, a new twin study of hip and knee OA concordance, an extensive study of GDF5 evolution, analyses of the contribution of Dnmt3a to OA, a description of DNA methylation in a nonhuman primate model of OA, and an integrated, multi-omics analysis of DNA methylation, mRNA, and protein expression in human OA samples, among others. A variety of micro- and a few circular-RNA studies were also published, highlighting the importance of noncoding RNA in both the pathogenesis and potential treatment of OA. CONCLUSION: Although publications have decreased slightly in the last year, genetics and epigenetics continue to be a topic of substantial research in OA, and considerable progress continues to be made in the field.
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Epigénesis Genética , Osteoartritis/genética , Epigénesis Genética/genética , Predisposición Genética a la Enfermedad/genética , HumanosRESUMEN
Systemic lupus erythematosus is a chronic autoimmune disease that can be associated with a variety of haematological manifestations. We identified 76 patients with haemolytic anaemia in a cohort of 1251 unrelated female lupus patients enrolled in our studies. The presence of the various American College of Rheumatology clinical criteria for lupus and serological specificities were determined in lupus patients with haemolytic anaemia and compared with a group of race-matched control lupus patients without haemolytic anaemia. Clinical data were obtained from medical records, and serological specificities were determined in our clinical immunology laboratory at OMRF. The presence of haemolytic anaemia in lupus patients was associated with a higher frequency of proteinuria (OR = 2.70, P = 0.000031), urinary cellular casts (OR = 2.83, P = 0.000062), seizures (OR = 2.96, P = 0.00024), pericarditis (OR = 2.21, P = 0.0019), pleuritis (OR = 1.72, P = 0.028) and lymphopenia (OR = 1.79, P = 0.015). These findings were independent of the presence of thrombocytopenia, which was approximately five times more common in lupus patients with haemolytic anaemia. Lupus patients with haemolytic anaemia were about 8 years younger than lupus patients without haemolytic anaemia at the time of disease onset (P = 0.000001). In the absence of thrombocytopenia, lupus patients with haemolytic anaemia were approximately two times more likely to have anti-dsDNA antibodies (P = 0.024). The presence of haemolytic anaemia is associated with a subset of lupus characterized by a younger age of disease onset, and a more severe disease with a higher likelihood of renal involvement, seizures, serositis and other cytopenias.
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Anemia Hemolítica/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Autoanticuerpos/sangre , Estudios de Cohortes , Femenino , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/etnologíaRESUMEN
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies against a host of nuclear antigens. The pathogenesis of lupus is incompletely understood. Environmental factors may play a role via altering DNA methylation, a mechanism regulating gene expression. In lupus, genes including CD11a and CD70 are overexpressed in T cells as a result of promoter hypomethylation. T-cell DNA methyltransferase expression is regulated in part by the extracellular signal-regulated kinase (ERK) signaling pathway. In this study, we investigate the effects of decreased ERK pathway signaling in T cells using transgenic animals. We generated a transgenic mouse that inducibly expresses a dominant-negative MEK in T cells in the presence of doxycycline. We show that decreased ERK pathway signaling in T cells results in decreased expression of DNA methyltransferase 1 and overexpression of the methylation-sensitive genes CD11a and CD70, similar to T cells in human lupus. Our transgenic animal model also develops anti-dsDNA antibodies. Interestingly, microarray expression assays revealed overexpression of several interferon-regulated genes in the spleen similar to peripheral blood cells of lupus patients. This model supports the contention that ERK pathway signaling defects in T cells contribute to the development of autoimmunity.
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Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación de la Expresión Génica , Interferones/metabolismo , Lupus Eritematoso Sistémico/inmunología , Linfocitos T/enzimología , Animales , Antígeno CD11a/genética , Antígeno CD11a/metabolismo , Ligando CD27/genética , Ligando CD27/metabolismo , Separación Celular/métodos , Células Cultivadas , Modelos Animales de Enfermedad , Doxiciclina/farmacología , Humanos , Interferones/genética , Lupus Eritematoso Sistémico/enzimología , Metilación , Metiltransferasas/genética , Metiltransferasas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Modelos Genéticos , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Proteínas Represoras/análisis , Proteínas Represoras/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
Systemic lupus erythematosus is a chronic, relapsing autoimmune disease that can affect multiple organ systems. An increased prevalence of drug allergy has been reported in lupus patients compared with the general population. Using a cohort of 417 lupus patients, we found a history of sulpha allergy in 27.3% of patients. European-American lupus patients with sulpha allergy are about two times more likely to suffer from lymphopenia, two times more likely to have anti-Ro autoantibody, and four times less likely to have anti-nRNP antibodies compared with lupus patients without a reported sulpha allergy (P = 0.0075, 0.025, and 0.032, respectively). In African-American lupus patients, a history of sulpha allergy was associated with over three times increased odds of developing pericarditis (P = 0.005).
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Hipersensibilidad a las Drogas/epidemiología , Lupus Eritematoso Sistémico/inmunología , Sulfonamidas/efectos adversos , Adulto , Anticuerpos Antinucleares/sangre , Autoanticuerpos/sangre , Hipersensibilidad a las Drogas/etnología , Femenino , Humanos , Masculino , Ribonucleoproteínas/inmunologíaRESUMEN
Inositol phosphorylceramide (IPC) synthase is an enzyme common to fungi and plants that catalyzes the transfer of phosphoinositol from phosphatidylinositol to ceramide to form IPC. The reaction is a key step in fungal sphingolipid biosynthesis and the target of the antibiotics galbonolide A, aureobasidin A, and khafrefungin. As a first step toward understanding the antifungal spectrum of IPC synthase inhibitors, we examined the sensitivity of IPC synthase to aureobasidin A in membrane preparations of Candida species (Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, and C. krusei) and Aspergillus species (Aspergillus fumigatus, A. flavus, A. niger, and A. terreus). As expected, preparations from the five Candida species, all exquisitely susceptible to aureobasidin A (MICs, <2 microgram/ml), had IPC synthase activity (specific activity, 50 to 400 pmol/min/mg of protein) sensitive to aureobasidin A (50% inhibitory concentrations [IC(50)s], 2 to 4 ng/ml). Surprisingly, preparations from the four Aspergillus species, including A. fumigatus and A. flavus, which are intrinsically resistant to aureobasidin A (MICs, >50 microgram/ml), had IPC synthase activity (specific activity, 1 to 3 pmol/min/mg of protein) also sensitive to aureobasidin A (IC(50)s, 3 to 5 ng/ml). The mammalian multidrug resistance modulators verapamil, chlorpromazine, and trifluoperazine lowered the MIC of aureobasidin A for A. fumigatus from >50 microgram/ml to 2 to 3 microgram/ml, suggesting that the resistance of this major fungal pathogen is the result of increased efflux.
Asunto(s)
Antifúngicos/farmacología , Aspergillus/efectos de los fármacos , Candida/efectos de los fármacos , Depsipéptidos , Hexosiltransferasas/antagonistas & inhibidores , Aspergillus/enzimología , Candida/enzimología , Farmacorresistencia Microbiana , Inhibidores Enzimáticos/farmacología , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Péptidos Cíclicos/farmacologíaRESUMEN
OBJECTIVE: Large-volume paracentesis is a safe and effective means of treating patients with refractory ascites. However, there is limited information regarding the need for ascitic fluid studies in asymptomatic outpatients presenting for therapeutic paracentesis. The aim of this prospective study was to define the incidence and natural history of peritoneal fluid infection in asymptomatic outpatients undergoing therapeutic paracentesis. METHODS: Over a 13-month period, 118 therapeutic paracenteses were performed in 29 outpatients with decompensated cirrhosis (Child-Pugh class B = 38%, C = 62%). After a brief medical history and physical examination, ascitic fluid cell count with differential and culture were obtained from all participating subjects. Seven (24%) of the subjects were receiving norfloxacin prophylaxis, accounting for antibiotic coverage during 40% of the procedures performed. The clinical course and outcome of study subjects during a mean follow-up of 137 days was reviewed. RESULTS: All 118 (100%) of the ascitic fluid samples demonstrated absolute neutrophil counts of <250/mm3 (mean = 6.5 +/- 22.5 pmn/mm3). Asymptomatic bacterascites was identified from three of the 118 (2.5%) fluid samples, but all of these subjects spontaneously recovered without treatment or sequelae. During follow-up, six episodes of symptomatic or hospital-associated peritoneal fluid infection were identified in study participants, emphasizing the importance of fluid studies in other clinical settings. CONCLUSIONS: Although further studies are needed, the routine culture of ascitic fluid in asymptomatic outpatients with refractory ascites requiring therapeutic paracentesis may not be necessary when there is a low index of suspicion for occult infection. In circumstances of clinical uncertainty, however, obtaining ascitic fluid cell counts with differential is recommended to insure patient safety.
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Atención Ambulatoria , Ascitis/terapia , Infecciones Bacterianas/diagnóstico , Paracentesis , Peritonitis/diagnóstico , Adulto , Anciano , Antiinfecciosos/uso terapéutico , Profilaxis Antibiótica , Ascitis/etiología , Líquido Ascítico/citología , Líquido Ascítico/microbiología , Infecciones Bacterianas/etiología , Infecciones Bacterianas/prevención & control , Femenino , Humanos , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Norfloxacino/uso terapéutico , Peritonitis/etiología , Peritonitis/prevención & control , Estudios ProspectivosRESUMEN
Approximately 4 million Americans are infected with the hepatitis C virus (HCV). Most patients with hepatitis C have no symptoms until cirrhosis is established. Thus, initial diagnosis and management of hepatitis C rely on primary care physicians identifying and screening high-risk individuals. We administered a survey to 1,233 primary care physicians in a health maintenance organization (HMO) in April 1997 to assess their knowledge of the risk factors for HCV infection and approach to the management of 2 hypothetical HCV antibody-positive patients, 1 with elevated and the other with normal alanine transaminase (ALT). Four hundred four (33%) physicians returned the survey. Ninety percent of respondents correctly identified the risk factors for HCV infection, but 20% still considered blood transfusion in 1994 as a significant risk factor for HCV infection. Sixty-two percent of respondents would refer HCV antibody-positive patients with abnormal transaminase levels, but 33% would follow these patients themselves, even though none of the respondents had treated any hepatitis C patient on their own. Forty-three percent of respondents overestimated, while 29% did not know the efficacy of interferon treatment. Sixty-five percent of respondents would retest patients for HCV antibody, regardless of risk factors and transaminase levels. We found that most primary care physicians correctly identified the significant risk factors for HCV infection and appropriately managed the 2 hypothetical patients, but there was considerable confusion about the use of HCV tests and the effectiveness of treatment. Educational programs for primary care physicians are needed to implement hepatitis C screening and to initiate further evaluation and management of those who test positive.
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Hepatitis C/tratamiento farmacológico , Atención Primaria de Salud , Hepatitis C/etiología , Anticuerpos contra la Hepatitis C/sangre , Humanos , Factores de Riesgo , Reacción a la TransfusiónRESUMEN
Hepatic hydrothorax is a relatively infrequent but potentially serious complication of cirrhosis resulting from the accumulation of ascitic fluid in the chest cavity. Medical management is initially directed at controlling ascites formation, but invasive therapeutic procedures may be required if symptoms persist. The aim of this study was to report on the long-term efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) placement to reduce portal hypertension in 12 consecutive subjects with refractory hepatic hydrothorax. Most subjects had evidence of advanced cirrhosis of varying causes (Child-Pugh class A, 1; B, 5; C, 6). Mean subject age was 54 years, and subjects were followed up for a mean of 173 days (range, 7-926 days). The portosystemic pressure gradient after TIPS was reduced to <12 mmHg in all cases. Periprocedural morbidity was noted in 2 subjects, and 30-day survival after TIPS placement was 75%. Overall, 58% of subjects experienced either a complete or partial response following TIPS placement. Subject response did not correlate with age, baseline creatinine clearance, or Child-Pugh score. Cumulative subject survival was 42%, and 4 of the 5 long-term survivors required eventual liver transplantation. Subject age >65 years was associated with early mortality after TIPS placement, but this trend was not statistically significant. All 4 subjects undergoing liver transplantation required perioperative pleural fluid drainage, but only 1 subject has experienced recurrent effusion. We conclude that TIPS may be a safe and effective temporizing treatment for carefully selected patients with refractory hepatic hydrothorax. However, patient survival is limited after TIPS and is primarily determined by availability of liver transplantation.
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Hidrotórax/cirugía , Cirrosis Hepática/complicaciones , Trasplante de Hígado , Derivación Portosistémica Intrahepática Transyugular , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Hidrotórax/etiología , Hidrotórax/mortalidad , Hipertensión Portal/complicaciones , Hipertensión Portal/mortalidad , Hipertensión Portal/cirugía , Cirrosis Hepática/mortalidad , Cirrosis Hepática/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Recurrencia , Estudios Retrospectivos , Seguridad , Tasa de Supervivencia , Resultado del TratamientoAsunto(s)
Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Úlcera Péptica/prevención & control , Antiácidos/uso terapéutico , Antibacterianos/uso terapéutico , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Bismuto/uso terapéutico , Estudios de Seguimiento , Humanos , Metronidazol/uso terapéutico , Naproxeno/efectos adversos , Naproxeno/uso terapéutico , Úlcera Péptica/etiología , Estudios Prospectivos , Factores de Riesgo , Método Simple Ciego , Tetraciclina/uso terapéuticoAsunto(s)
Enfermedad Veno-Oclusiva Hepática/etiología , Trasplante de Riñón/efectos adversos , Adulto , Femenino , Enfermedad Veno-Oclusiva Hepática/diagnóstico por imagen , Enfermedad Veno-Oclusiva Hepática/patología , Enfermedad Veno-Oclusiva Hepática/cirugía , Humanos , Hígado/patología , Trasplante de Hígado , Pielonefritis/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Of the three primary phylogenetic domains--Archaea (archaebacteria), Bacteria (eubacteria), and Eucarya (eukaryotes)--Archaea is the least understood in terms of its diversity, physiologies, and ecological panorama. Although many species of Crenarchaeota (one of the two recognized archaeal kingdoms sensu Woese [Woese, C. R., Kandler, O. & Wheelis, M. L. (1990) Proc. Natl. Acad. Sci. USA 87, 4576-4579]) have been isolated, they constitute a relatively tight-knit cluster of lineages in phylogenetic analyses of rRNA sequences. It seemed possible that this limited diversity is merely apparent and reflects only a failure to culture organisms, not their absence. We report here phylogenetic characterization of many archaeal small subunit rRNA gene sequences obtained by polymerase chain reaction amplification of mixed population DNA extracted directly from sediment of a hot spring in Yellowstone National Park. This approach obviates the need for cultivation to identify organisms. The analyses document the existence not only of species belonging to well-characterized crenarchaeal genera or families but also of crenarchaeal species for which no close relatives have so far been found. The large number of distinct archaeal sequence types retrieved from this single hot spring was unexpected and demonstrates that Crenarchaeota is a much more diverse group than was previously suspected. The results have impact on our concepts of the phylogenetic organization of Archaea.
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Archaea/genética , Microbiología del Agua , Archaea/clasificación , Archaea/aislamiento & purificación , Secuencia de Bases , Clonación Molecular , Cartilla de ADN/genética , ADN Bacteriano/genética , ADN Ribosómico/genética , Ecosistema , Agua Dulce , Variación Genética , Calor , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa , ARN Bacteriano/genética , ARN Ribosómico/genética , WyomingRESUMEN
A prospective study of growth hormone, insulin-like growth factor (IGF-1), and cortisol secretion was undertaken in six adults with burn injury. Serum concentrations of growth hormone and IGF-1 were low in all patients during the first 2 weeks of hospitalization. The mean growth hormone level was 4.35 +/- 0.83 micrograms/L on day 1 and 1.70 +/- 0.50 micrograms/L on day 13. The mean serum concentration of IGF-1, which reflects overall growth hormone secretion, was 0.43 +/- 0.09 U/ml on day 1 and 0.61 +/- 0.11 U/ml on day 13; these values are distinctly low. After 3 to 4 weeks, IGF-1 concentrations increased to the mid-normal range, whereas growth hormone values did not change. Morning plasma cortisol concentrations were modestly elevated; however, urine free cortisol concentrations, which reflect total cortisol secretion, were elevated 2 to 28 times above normal values at the time of admission (mean, 443.5 +/- 323.7 nmol/L). Urinary free cortisol concentrations remained elevated after 2 weeks (mean, 230.5 +/- 94.5 nmol/L). Patients with burn injury have inappropriately low growth hormone secretion and IGF-1 production in spite of the stress of the injury and more than adequate nutritional therapy.
Asunto(s)
Quemaduras/metabolismo , Hormona del Crecimiento/metabolismo , Hidrocortisona/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Adulto , Superficie Corporal , Femenino , Hormona del Crecimiento/sangre , Hormona del Crecimiento/orina , Hospitalización , Humanos , Hidrocortisona/sangre , Hidrocortisona/orina , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Canine gastric dilatation-volvulus (GDV) is a naturally acquired condition of large-breed dogs primarily and is associated with high mortality. The clinical course suggests that reperfusion injury may be important in the pathogenesis of GDV. To evaluate the role of xanthine oxidase and iron-dependent lipid peroxidation (which are purported mechanisms of reperfusion injury) in the pathogenesis of GDV-related mortality, we created experimental GDV in 21 dogs. These dogs were then treated with either allopurinol (a xanthine oxidase inhibitor), U74006F (an experimental lipid peroxidation inhibitor), or saline solution (NaCl, 0.85%). Three of 8 dogs died in the allopurinol-treated group, none of 5 died in the U74006F-treated group, and 4 of 8 died in the saline solution-treated group. Tissue malondialdehyde concentration, a nonspecific indicator of lipid peroxidation, was significantly (P less than 0.05) greater in the duodenum, jejunum, colon, liver, and pancreas of the saline-solution treated and allopurinol-treated dogs than in the same tissues of the U74006F-treated dogs after surgical correction of the GDV (ie, during reperfusion), compared with malondialdehyde concentrations determined before inducing GDV. The results of this study support the concept that lipid peroxidation associated with reperfusion injury is important in the pathogenesis and high mortality of canine GDV. Furthermore, this lipid peroxidation and mortality may be preventable by appropriate and timely treatment.
Asunto(s)
Alopurinol/uso terapéutico , Enfermedades de los Perros/prevención & control , Pregnatrienos/uso terapéutico , Daño por Reperfusión/veterinaria , Vólvulo Gástrico/veterinaria , Animales , Enfermedades de los Perros/cirugía , Perros , Peróxidos Lipídicos/antagonistas & inhibidores , Daño por Reperfusión/prevención & control , Vólvulo Gástrico/cirugíaRESUMEN
In cells exposed to glucocorticoids at 37 degrees C activated glucocorticoid-receptor complexes (complexes with affinity for nuclei and DNA) are formed after nonactivated complexes. Activation thus appears to be an obligatory physiological process. To investigate this process we have characterized cytoplasmic complexes formed in rat thymocytes at 0 and 37 degrees C. Complexes in cytosols stabilized with molybdate were analyzed by sucrose gradient centrifugation and by chromatography on DNA-cellulose, DEAE-cellulose, and agarose gels. Two major complexes were observed: the nonactivated complex, eluted from DEAE at approximately 200 mM KCl, was formed at 0 and 37 degrees C, gave S20,w = 9.2 S, Stokes radius = 8.3 nm, and calculated Mr = 330,000; the activated complex, eluted from DEAE at approximately 50 mM KCl, appeared only at 37 degrees C, gave S20,w = 4.8 S, Stokes radius = 5.0 nm, and Mr = 100,000. A third, minor complex, probably mero-receptor, which appeared mainly at 37 degrees C, bound to neither DNA nor DEAE, and gave S20,w = 2.9 S, Stokes radius = 2.3 nm, and Mr = 27,000. With three small columns in series (DNA-cellulose, DEAE-cellulose and hydroxylapatite), the three complexes can be separated in 5-10 min. By this method we have examined the stability of complexes under our conditions. We conclude that in intact thymus cells glucocorticoid-receptor complexes occur principally in two forms, nonactivated and activated, and that activation is accompanied by a large reduction in size. The origin of the mero-receptor complex remains uncertain.