RESUMEN
AimsIn the past few years, there has been an unprecedented increase in the number of forcibly displaced migrants worldwide, of which a substantial proportion is refugees and asylum seekers. Refugees and asylum seekers may experience high levels of psychological distress, and show high rates of mental health conditions. It is therefore timely and particularly relevant to assess whether current evidence supports the provision of psychosocial interventions for this population. We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the efficacy and acceptability of psychosocial interventions compared with control conditions (treatment as usual/no treatment, waiting list, psychological placebo) aimed at reducing mental health problems in distressed refugees and asylum seekers. METHODS: We used Cochrane procedures for conducting a systematic review and meta-analysis of RCTs. We searched for published and unpublished RCTs assessing the efficacy and acceptability of psychosocial interventions in adults and children asylum seekers and refugees with psychological distress. Post-traumatic stress disorder (PTSD), depressive and anxiety symptoms at post-intervention were the primary outcomes. Secondary outcomes include: PTSD, depressive and anxiety symptoms at follow-up, functioning, quality of life and dropouts due to any reason. RESULTS: We included 26 studies with 1959 participants. Meta-analysis of RCTs revealed that psychosocial interventions have a clinically significant beneficial effect on PTSD (standardised mean difference [SMD] = -0.71; 95% confidence interval [CI] -1.01 to -0.41; I2 = 83%; 95% CI 78-88; 20 studies, 1370 participants; moderate quality evidence), depression (SMD = -1.02; 95% CI -1.52 to -0.51; I2 = 89%; 95% CI 82-93; 12 studies, 844 participants; moderate quality evidence) and anxiety outcomes (SMD = -1.05; 95% CI -1.55 to -0.56; I2 = 87%; 95% CI 79-92; 11 studies, 815 participants; moderate quality evidence). This beneficial effect was maintained at 1 month or longer follow-up, which is extremely important for populations exposed to ongoing post-migration stressors. For the other secondary outcomes, we identified a non-significant trend in favour of psychosocial interventions. Most evidence supported interventions based on cognitive behavioural therapies with a trauma-focused component. Limitations of this review include the limited number of studies collected, with a relatively low total number of participants, and the limited available data for positive outcomes like functioning and quality of life. CONCLUSIONS: Considering the epidemiological relevance of psychological distress and mental health conditions in refugees and asylum seekers, and in view of the existing data on the effectiveness of psychosocial interventions, these interventions should be routinely made available as part of the health care of distressed refugees and asylum seekers. Evidence-based guidelines and implementation packages should be developed accordingly.
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Ansiedad/terapia , Depresión/terapia , Aceptación de la Atención de Salud/psicología , Psicoterapia/métodos , Refugiados/psicología , Trastornos por Estrés Postraumático/terapia , Estrés Psicológico/terapia , Ansiedad/psicología , Depresión/psicología , Femenino , Humanos , Masculino , Salud Mental , Evaluación de Resultado en la Atención de Salud , Aceptación de la Atención de Salud/etnología , Ensayos Clínicos Controlados Aleatorios como Asunto , Trastornos por Estrés Postraumático/psicología , Estrés Psicológico/psicologíaRESUMEN
Freeze-drying is the preferred method for stabilizing live, attenuated virus vaccines. After decades of research on several aspects of the process like the stabilization and destabilization mechanisms of the live, attenuated viruses during freeze-drying, the optimal formulation components and process settings are still matter of research. The molecular complexity of live, attenuated viruses, the multiple destabilization pathways and the lack of analytical techniques allowing the measurement of physicochemical changes in the antigen's structure during and after freeze-drying mean that they form a particular lyophilization challenge. The purpose of this review is to overview the available information on the development of the freeze-drying process of live, attenuated virus vaccines, herewith focusing on the freezing and drying stresses the viruses can undergo during processing as well as on the mechanisms and strategies (formulation and process) that are used to stabilize them during freeze-drying.
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Liofilización/métodos , Vacunas Atenuadas/química , Vacunas Virales/química , Membrana Celular/química , Crioprotectores/química , Concentración de Iones de Hidrógeno , Hielo , Concentración Osmolar , Tecnología Farmacéutica , Proteínas Virales/químicaRESUMEN
AIMS/HYPOTHESIS: This study is a 19 year observational follow-up of a pragmatic open multicentre cluster-randomised controlled trial of 6 years of structured personal diabetes care starting from diagnosis. METHODS: A total of 1,381 patients aged ≥ 40 years and newly diagnosed with type 2 diabetes were followed up in national registries for 19 years. Clinical follow-up was at 6 and 14 years after diabetes diagnosis. The original 6 year intervention included regular follow-up and individualised goal setting, supported by prompting of doctors, clinical guidelines, feedback and continuing medical education (ClinicalTrials.gov NCT01074762). The registry-based endpoints were: incidence of any diabetes-related endpoint; diabetes-related death; all-cause mortality; myocardial infarction (MI); stroke; peripheral vascular disease; and microvascular disease. RESULTS: At 14 year clinical follow-up, group differences in risk factors from the 6 year follow-up had levelled out, although the prevalence of (micro)albuminuria and level of triacylglycerols were lower in the intervention group. During 19 years of registry-based monitoring, all-cause mortality was not different between the intervention and comparison groups (58.9 vs 62.3 events per 1,000 patient-years, respectively; for structured personal care, HR 0.94, 95% CI 0.83, 1.08, p = 0.40), but a lower risk emerged for fatal and non-fatal MI (27.3 vs 33.5, HR 0.81, 95% CI 0.68, 0.98, p = 0.030) and any diabetes-related endpoint (69.5 vs 82.1, HR 0.83, 95% CI 0.72, 0.97, p = 0.016). These differences persisted after extensive multivariable adjustment. CONCLUSIONS/INTERPRETATION: In concert with features such as prompting, feedback, clinical guidelines and continuing medical education, individualisation of goal setting and drug treatment may safely be applied to treat patients newly diagnosed with type 2 diabetes to lower the risk of diabetes complications.
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Diabetes Mellitus Tipo 2/terapia , Autocuidado , Adulto , Anciano , Complicaciones de la Diabetes/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Sistema de Registros , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
INTRODUCTION: We investigated to which degree a sample of 143 general practitioners in the County of Copenhagen would screen their patients for problem drinking by using The Alcohol Use Disorders Identification Test (AUDIT). Furthermore, among users of AUDIT, we aimed to describe the doctors' perception of using it. METHODS: Eighty-one out of the 143 doctors requested AUDIT. However, after they had had the possibility of using AUDIT, only 38 had handed an AUDIT to at least one patient. These 38 doctors were asked to answer a questionnaire on which this study is based. RESULTS: Thirty-two percent (12/38) of the doctors handed out an AUDIT in more than 14 days, and 21% (8/38) gave at least 100 patients an AUDIT. The general practitioners worked a median of 20 days in their practice during the study period. Only 14% (5/36) would screen all their patients in the future, and 42% (15/36) only when they suspected problem drinking. Sixty-four percent (22/34) of the doctors stated that handing all patients an AUDIT was much too time-consuming, 50% (17/34) stated that financial incentives are necessary, and 53% (18/34) questioned whether the patients wanted an AUDIT. Sixty-six percent (23/35) of the doctors judged that they had improved in detecting patients with alcohol related problems. CONCLUSION: The participating general practitioners were not interested in handing all patients an AUDIT. Major barriers were lack of time and financial incentives and furthermore the doctors questioned whether the patients wanted an AUDIT. However, half of the doctors would use AUDIT for certain patients, especially when they suspected problem drinking.
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Consumo de Bebidas Alcohólicas , Alcoholismo/diagnóstico , Medicina Familiar y Comunitaria , Tamizaje Masivo , Adulto , Alcoholismo/prevención & control , Actitud del Personal de Salud , Dinamarca , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Médicos de Familia/psicología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Early diagnosis and treatment are shown to improve survival of breast and ovarian cancer. Identification and medical follow-up of high-risk groups may be important for early diagnosis. METHODS: A prospective study of 845 women from breast/ovarian- and ovarian cancer kindreds who were classified according to pre-set inclusion criteria (Table I), were offered genetic counseling and annual medical examinations of breasts and ovaries. The material consisted of three series: 1) 754 unaffected women, 2) 49 women with breast cancer, and 3) 42 women with ovarian cancer. RESULTS: In series 1) nine ovarian cancers and 20 breast cancers, in series 2) seven ovarian cancers, and in series 3) three breast cancers were found. All but one of the ovarian cancers were 40 years or older, and 4/16 (25%) were Borderline cancer. All breast cancers were 30 years or older, and 89% were detected before spread. CONCLUSIONS: This is to our knowledge the first prospective report of the combined breast/ovarian cancer findings in breast/ovarian cancer kindreds. A woman with both breast and ovarian cancer is the hallmark of inherited breast/ovarian cancer, and 50% of the ovarian cancers were detected in these families. Borderline ovarian cancer may represent a manifestation of this syndrome. If prophylactic oophorectomy prevents ovarian cancer, oophorectomy at age 45 would have prevented 75% of such cancers. Based on these results we revised our protocol for annual follow-up in these kindreds: 1) clinical breast examination and mammography (ultrasound/cytology if indicated) from 30 years of age, 2) gynecologic examination (including vaginal ultrasound, serum-CA125) from 35 years of age, and 3) discuss oophorectomy at 45 years of age.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/prevención & control , Neoplasias Ováricas/genética , Neoplasias Ováricas/prevención & control , Adolescente , Adulto , Anciano , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Antígeno Ca-125/análisis , Femenino , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , Ovariectomía , Estudios Prospectivos , Ultrasonografía MamariaRESUMEN
BACKGROUND: GPs are in a key position to screen the population for problem drinking. However, so far this has not been extensively undertaken in general practice. Thus, studies relating to encouraging the undertaking in general practice of screening and initiating a brief intervention for problem drinking are needed. OBJECTIVES: We aimed to compare three approaches direct mail, telephone contact and academic detailing to encourage GPs to undertake screening and a brief intervention (SBI) for problem drinking. METHODS: A total of 143 GPs in Copenhagen County were randomly assigned to the three approaches. The outcome measures were the proportion of GPs who requested the SBI package (uptake rate) and the fraction of GPs who started using the package (utilization rate). The costs of each approach were calculated. RESULTS: Compared with the direct mailing approach, uptake rates were significantly higher among GPs approached by telephone (30 versus 72%; P = 0.0001) and in the academic detailing approach (30 versus 67%; P = 0.0006). There was no significant difference between telephone contact and academic detailing (72 versus 67%; P = 0.75). There was a higher utilization rate in the academic detailing approach than in telephone contact (61 versus 31%; P = 0.023). There was no significant difference between direct mail and telephone contact (57 versus 31%; P = 0.16) or between direct mail and academic detailing (57 versus 61%; P = 0.95). The respective costs of the telephone and academic detailing approaches were 10 and 16 times that of the direct mailing approach. CONCLUSION: Telephone contact and academic detailing are more effective than direct mail in encouraging GPs to request an SBI package, but GPs who were approached by academic detailing were more likely to have utilized the package than GPs who were approached by telephone. The relatively high uptake and utilization rates obtained in the academic detailing approach suggest that this approach is to be preferred in encouraging a rapid uptake of SBI among GPs. However, the high costs associated with this approach need to be taken into consideration.
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Consumo de Bebidas Alcohólicas/prevención & control , Medicina Familiar y Comunitaria , Educación en Salud/métodos , Promoción de la Salud/métodos , Tamizaje Masivo/métodos , Adulto , Distribución de Chi-Cuadrado , Costos y Análisis de Costo , Recolección de Datos , Dinamarca , Difusión de Innovaciones , Femenino , Educación en Salud/economía , Educación en Salud/organización & administración , Humanos , Servicios de Información , Masculino , Tamizaje Masivo/economía , Persona de Mediana Edad , Evaluación de Programas y Proyectos de Salud , Proyectos de Investigación , Estadísticas no ParamétricasRESUMEN
Autoantibodies towards coagulation factor VIII is a rare disease, incidence 1 pr. 2.5-5 million/year. The symptoms are most often subcutaneous or intramuscular haemorrhages or uncontrollable bleeding after minimal traumas. Screening tests show prolonged activated partial thromboplastin time, normal prothrombin time and thrombocyte count. Production of autoantibodies is controlled by prednisolone which may be supplemented with chemotherapy, i.e. azathioprine. Bleeding can be controlled by using coagulation factor concentrates that bypass factor VIII. If diagnosed early, there is a good chance of both stopping bleeding and suppressing autoantibody production. In order to be able to detect patients at risk of having factor VIII autoantibodies, it is recommended to screen all bleeding patients using activated partial thromboplastin time, prothrombin time and thrombocyte count. All patients showing isolated prolonged activated partial thrombin time should be referred to a laboratory specialized in coagulation problems for immediate evaluation.
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Autoanticuerpos , Trastornos de la Coagulación Sanguínea/inmunología , Factor VIII/inmunología , Autoanticuerpos/análisis , Autoanticuerpos/biosíntesis , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Hemorragia/diagnóstico , Hemorragia/tratamiento farmacológico , Hemorragia/inmunología , HumanosAsunto(s)
Inmunosupresores/farmacocinética , Absorción Intestinal , Tacrolimus/farmacocinética , Trasplante Homólogo/fisiología , Vísceras/trasplante , Adulto , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Infusiones Intravenosas , Intubación , Masculino , Tacrolimus/administración & dosificación , Tacrolimus/uso terapéutico , Factores de Tiempo , Trasplante Homólogo/inmunologíaRESUMEN
An East Danish population of acquired haemophilia A (factor VIII inhibitors) patients are described in a retrospective survey. Fifteen patients attended the centre during the period 1981-1994. The epidemiology, clinical presentation, time from début until diagnosis and response to treatment are presented. Acquired factor VIII inhibitors are rare and without treatment the disease has a high mortality and morbidity. Inhibitors mostly develop among the elderly, independent of sex and almost half have no known underlying disease. When the diagnosis is clear, bleedings may be controlled and the patient may be cured by treatment that eliminates the inhibitor. Time until diagnosis varies a lot, for some patients it takes years. It is therefore important to be aware of the disease, so that time with risk of fatal bleeding is shortened as much as possible.
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Hemofilia A/etiología , Adulto , Anciano , Dinamarca/epidemiología , Diagnóstico Diferencial , Femenino , Hemofilia A/diagnóstico , Hemofilia A/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The creatine kinase/creatine phosphate (CK/CrP) system plays an important role in cellular energy homeostasis. CK isoenzymes, which reversibly generate ATP from CrP, are compartmentalized at cellular sites where energy is produced or utilized. It has been noted that the expression of CK is induced in cells infected by several DNA viruses, implicating a role for cellular energy modulation as an important step for efficient viral replication. A CK substrate analog, 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine; CCr), was tested in vitro for antiviral activity against a variety of herpes viruses and RNA viruses. Several members of the human herpes virus family were found to be sensitive to CCr, including herpes simplex types 1 and 2 (HSV-1 and HSV-2). varicella-zoster virus, and cytomegalovirus. When administered to mice infected vaginally with HSV-2, CCr significantly reduced mortality, reduced vaginal lesion scores, and lowered the titers of recoverable virus. This treatment combined with acyclovir appeared to enhance the antiviral effects of acyclovir. In a second model, mice infected intraperitoneally with HSV-2 and treated with CCr showed a significant increase in survival compared to placebo. We conclude that CCr is the first example of a new class of antiviral compounds that target the CK/CrP system.
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Creatinina/análogos & derivados , Herpesviridae/fisiología , Virus ARN/fisiología , Replicación Viral/efectos de los fármacos , Aciclovir/uso terapéutico , Animales , Creatinina/farmacología , Creatinina/uso terapéutico , Modelos Animales de Enfermedad , Farmacorresistencia Microbiana , Quimioterapia Combinada , Encefalitis/tratamiento farmacológico , Encefalitis/mortalidad , Femenino , Guanosina Trifosfato/análogos & derivados , Guanosina Trifosfato/farmacología , Guanosina Trifosfato/uso terapéutico , Herpes Genital/microbiología , Herpes Genital/mortalidad , Herpes Genital/prevención & control , Herpesviridae/efectos de los fármacos , Infecciones por Herpesviridae/tratamiento farmacológico , Infecciones por Herpesviridae/mortalidad , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Virus ARN/efectos de los fármacos , Tasa de SupervivenciaRESUMEN
1 A prescription database study was conducted to describe the out-patient utilization of neuroleptics in the Odense area (207,000 inhabitants) during a period of 1 year. 2 Neuroleptic drug use is widespread, the period prevalence being 2.45% of the population. 3 The prevalence increases with increasing age. Fifteen percent of the population aged 90 years or more received neuroleptic drugs in spite of the many warnings against side effects in the elderly. 4 Estimated daily doses of neuroleptics were considerably lower than the Defined Daily Dose, probably as a reflection of many neuroleptics being prescribed to non-psychotic patients, in whom lower doses are used. 5 For perphenazine, a comparison of estimated daily doses from this study with doses from patients whose treatment had been adjusted by plasma concentration monitoring showed that generally much lower doses were used by patients included in this study.
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Atención Ambulatoria/estadística & datos numéricos , Antipsicóticos/uso terapéutico , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Dinamarca , Utilización de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A young male with retroperitoneal recurrence of a germ cell tumour was successfully treated with chemotherapy. Four months after the last treatment a CT scan revealed hyperplasia of the thymus. A year after the last treatment the CT scan shows regression. A review of the literature demonstrates that 10% of patients treated for germ cell tumours develop a benign, reversible hyperplasia of the thymus within two years after treatment. Thus, benign hyperplasia of the thymus should be considered if a patient treated for germ cell tumour develops a tumour in the anterior mediastinum within two years.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Pulmonares/secundario , Neoplasias de Células Germinales y Embrionarias/secundario , Neoplasias Testiculares/secundario , Hiperplasia del Timo/inducido químicamente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Hiperplasia del Timo/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Woodchucks infected with woodchuck hepatitis virus (WHV) and ground squirrels infected with ground squirrel hepatitis virus (GSHV) both develop hepatocellular carcinoma (HCC), but WHV-associated tumors arise more frequently and much earlier in life. These differences are preserved when the oncogenic potentials of the two viruses are examined in the same host (woodchucks). We examined RNA and genomic DNA from tumors arising from WHV- and GSHV-infected woodchucks to determine whether these viruses use the same oncogenic pathway. N-myc RNA was not expressed in normal liver but was expressed in 10 of 13 WHV-associated HCCs examined. Southern blot analysis showed that 7 of 17 WHV-induced tumors (41%) contained rearrangements at N-myc loci due to viral genomic integration. Six of these seven inserts affected N-myc2, and most of these were at the 5' end of the gene. In contrast, only two of seven GSHV-induced woodchuck HCCs expressed N-myc RNA, and only 1 of the 16 tumors (6%) contained a rearranged N-myc allele. The GSHV-associated HCCs all contained numerous viral insertions, so the low frequency of integration into N-myc loci by GSHV was not due to a general block to integration. Four of sixteen GSHV-induced tumors harbored amplified c-myc alleles, and five of seven GSHV tumors tested contained elevated c-myc RNA levels. By contrast, enhanced c-myc RNA levels were observed in only 2 of 13 WHV-induced HCC. We conclude that N-myc overexpression is a regular feature of WHV- but not GSHV-associated hepatocarcinogenesis in a common host. In contrast, c-myc transcriptional deregulation is rarely encountered in WHV-induced HCC but is frequent in GSHV-induced HCC.
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Carcinoma Hepatocelular/genética , Regulación Viral de la Expresión Génica , Genes myc , Hepadnaviridae/genética , Neoplasias Hepáticas/genética , Animales , Secuencia de Bases , Carcinoma Hepatocelular/microbiología , ADN de Neoplasias/genética , Amplificación de Genes , Reordenamiento Génico , Neoplasias Hepáticas/microbiología , Marmota , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos/química , ARN Mensajero/genética , ARN Neoplásico/genéticaRESUMEN
The characteristics of cell-free translation systems prepared from unfertilized eggs and early cleavage stage embryos of the sea urchin, Strongylocentrotus purpuratus, closely reflect the developmentally regulated changes in protein synthesis initiation observed in vivo. Cell-free translation systems prepared over the first 0-6 h following fertilization show gradually increasing activities, mimicking the changes observed in vivo. The mechanisms underlying these increases are complex and occur at several levels. One factor contributing to the rise in protein synthetic rate is the gradual increase in eukaryotic initiation factor (eIF)-4 activity. This is correlated with the progressive inactivation of an inhibitor of eIF-4 function, which can be reactivated by in vitro manipulations. The relatively slow activation of eIF-4 follows similar kinetics to the increased utilization of maternal mRNA and ribosomes, in contrast to the rapid rise in maternal mRNA activation, and the increase in eIF-2B activity. This slow release from eIF-4 inhibition following a rapid release from eIF-2B inhibition and increased mRNA availability is reflected in the pattern of initiator tRNA binding to the small ribosomal subunit observed in cell-free translation systems. In translation systems from unfertilized eggs, initiator tRNA is unable to interact with the small ribosomal subunit, consistent with an initial block in both eIF-2B and eIF-4 activity. In translation systems from 30-min embryos, 48 S preinitiation complexes accumulate, reflecting the release from inhibition of mRNA availability and eIF-2B activity, but continued low activity of eIF-4. The accumulation of initiator tRNA in 48 S preinitiation complexes disappears gradually in translation systems from later embryos, as eIF-4 is slowly released from inhibition.
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Factores de Iniciación de Péptidos/metabolismo , Biosíntesis de Proteínas , Erizos de Mar/embriología , Animales , Blastocisto/metabolismo , Sistema Libre de Células , Embrión no Mamífero/metabolismo , Cinética , Proteínas/genética , ARN Mensajero/metabolismo , Ribosomas/metabolismo , Erizos de Mar/metabolismoRESUMEN
Ty3 is a Saccharomyces cerevisiae retrotransposon that integrates near the transcription initiation sites of polymerase III-transcribed genes. It is distinct from the copialike Ty1 and Ty2 retrotransposons of S. cerevisiae in both the sequences of encoded proteins and gene order. It is a member of the gypsylike family of retrotransposons which resemble animal retroviruses. This study was undertaken to investigate the nucleocapsid particle of a transpositionally active gypsylike retrotransposon. Characterization of extracts from cells in which Ty3 expression was induced showed the presence of Ty3 nucleoprotein complexes, or viruslike particles, that migrated on linear sucrose gradients with a size of 156S. These particles are composed of Ty3 RNA, full-length, linear DNA, and proteins. In this study, antibodies raised against peptides predicted from the Ty3 sequence were used to identify Ty3-encoded proteins. These include the capsid (26 kDa), nucleocapsid (9 kDa), and reverse transcriptase (55 kDa) proteins. Ty3 integrase proteins of 61 and 58 kDa were identified previously (L. J. Hansen and S. B. Sandmeyer, J. Virol. 64:2599-2607, 1990). Reverse transcriptase activity associated with the particles was measured by using exogenous and endogenous primer-templates. Immunofluorescence studies of cells overexpressing Ty3 revealed cytoplasmic clusters of immunoreactive proteins. Transmission electron microscopy showed that Ty3 viruslike particles are about 50 nm in diameter. Thus, despite the unusual position specificity of Ty3 upstream of tRNA-coding regions, aspects of the Ty3 life cycle are fundamentally similar to those of retroviruses.
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Elementos Transponibles de ADN , Proteínas Fúngicas/genética , Genes Fúngicos , Saccharomyces cerevisiae/genética , Secuencia de Aminoácidos , Cápside/química , ADN de Hongos/genética , Proteínas Fúngicas/química , Expresión Génica , Microscopía Electrónica , Datos de Secuencia Molecular , Nucleoproteínas/química , Péptidos/química , ARN de Hongos/genética , ADN Polimerasa Dirigida por ARN/genética , Retroviridae/genética , Saccharomyces cerevisiae/ultraestructuraRESUMEN
One of the factors involved in the postfertilization activation of protein synthesis in the sea urchin, Strongylocentrotus purpuratus, is the activation of eIF-2B, the initiation factor responsible for guanine nucleotide exchange on eIF-2. Cell-free translation systems from unfertilized eggs are stimulated by added eIF-2B, although this dependency is rapidly lost in translation systems prepared at various times following fertilization. Cell-free translation systems prepared from unfertilized eggs show significantly lower eIF-2B activities than those prepared from 2-h embryos. However, the provision of an NADPH regeneration system significantly stimulates eIF-2B activity in egg extracts and, in addition, stimulates both binding of initiator tRNA to the small ribosomal subunit and protein synthetic activity. These data suggest that the activation of eIF-2B following fertilization reflects the fertilization-induced increase in NADPH levels.
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Fertilización , Proteínas/metabolismo , Animales , Sistema Libre de Células , Embrión no Mamífero/metabolismo , Glucofosfatos/farmacología , Factores de Intercambio de Guanina Nucleótido , NADP/metabolismo , Óvulo/efectos de los fármacos , Óvulo/metabolismo , Oxidación-Reducción , Biosíntesis de Proteínas/efectos de los fármacos , Erizos de MarRESUMEN
Activation of the complement system, the main humoral mediator of inflammation, is restrained by the action of enzyme inhibitors including alpha 1-antitrypsin. Deficiency leads to chronic liver disease in about one in five children with this genetic defect. Complement activation was investigated in 34 children with alpha 1 AT deficiency (12 with minimal, 10 with moderate, and 12 with severe liver disease) and in 38 sex and age matched normal children by measuring the complement parent molecules C3, C4, the C3d fragment and by calculating the C3d:C3 ratio. C3 and C4 were lower in children with severe liver disease compared with controls, indicating impairment of hepatic protein synthesis or complement consumption. The C3d activation fragment was higher in all the patient groups when compared with controls while the C3d:C3 ratio, a measure of activation independent of the concentrations of the parent molecule, was higher in patients than in controls and increased with the degree of disease severity. These results suggest that complement may have a role in the pathogenesis of the chronic liver disease associated with alpha 1AT deficiency.
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Activación de Complemento/fisiología , Hepatopatías/inmunología , Deficiencia de alfa 1-Antitripsina , Adolescente , Niño , Preescolar , Enfermedad Crónica , Complemento C3/análisis , Complemento C3d/análisis , Complemento C4/análisis , Femenino , Humanos , Lactante , Hepatopatías/genética , Hepatopatías/metabolismo , Masculino , FenotipoRESUMEN
To elucidate the biological importance of intrahepatic hepatitis D virus antigen, its expression was correlated with biochemical and histological inflammatory activity in 98 biopsy specimens from 68 patients seropositive for total antibody to the virus. Seventy five specimens were positive for intrahepatic nuclear antigen for HDV antigen accompanied by cytoplasmic HDV antigen in only one biopsy specimen. This group had significantly higher serum transaminase activities and inflammatory activity than the remaining cases that were negative for HDV antigen. Among the group positive for HDV antigen, there was no correlation between the proportion of hepatocytes containing HDV antigen and either serum transaminase activity or histological inflammatory indices. In 22 HDV antigen positive patients who had follow up biopsy specimens taken at a median of two years, the proportion with cirrhosis increased from 36% to 73%. Serum transaminase activities remained the same during this period, but the proportion of HDV antigen positive cells dropped. Follow up of 51 patients showed that 21 died or underwent liver transplantation within three years. The absence of an association between intrahepatic HDV antigen expression and progression of histological liver damage does not support the view that HDV is directly cytopathic to hepatocytes. Immune mediated mechanisms may have a role in the pathogenesis of chronic liver disease related to HDV infection.