Mitogen-Activated Protein Kinase Phosphatase-1 Is Overexpressed in Non-Small Cell Lung Cancer and Is an Independent Predictor of Outcome in Patients

An increase in the activity of the mitogen-activated protein kinases (MAPKs) has been correlated with a more malignant phenotype in several tumor models in vitro and in vivo. A key regulatory mechanism of the MAPKs [extracellular signal-regulated kinase (ERK); c-jun NH(2)-terminal kinase (JNK); and p38] is the dual specificity phosphatase CL100, also called MAPK phosphatase-1 (MKP-1). This study was designed to examine the involvement of CL100/MKP-1 and stress-related MAPKs in lung cancer. EXPERIMENTAL DESIGN: We assessed the expression of CL100/MKP-1 and the activation of the MAPKs in a panel of 18 human cell lines [1 primary normal bronchial epithelium, 8 non-small cell lung cancer (NSCLC), 7 small cell lung cancer (SCLC), and 2 carcinoids] and in 108 NSCLC surgical specimens. RESULTS: In the cell lines, CL100/MKP-1 expression was substantially higher in NSCLC than in SCLC. P-ERK, P-JNK, and P-p38 were activated in SCLC and NSCLC, but the degree of their activation was variable. Immunohistochemistry in NSCLC resection specimens showed high levels of CL100/MKP-1 and activation of the three MAPK compared with normal lung. In univariate analysis, no relationship was found among CL100/MKP-1 expression and P-ERK, P-JNK, or P-p38. Interestingly, high CL100/MKP-1 expression levels independently predicted improved survival in multivariate analysis. JNK activation associated with T(1-2) and early stage, whereas ERK activation correlated with late stages and higher T and N. Neither JNK nor ERK activation were independent prognostic factors when studied for patient survival. CONCLUSIONS: Our data indicate the relevance of MAPKs and CL100/MKP-1 in lung cancer and point at CL100/MKP-1 as a potential positive prognostic factor in NSCLC. Finally, our study supports the search of new molecular targets for lung cancer therapy within the MAPK signaling pathway

Portuguese Ministers, 1851-1999: Social Background and Paths to Power

Disponível em: http://193.136.113.6/Opac/Pages/Search/Results.aspx?SearchText=UID=bb8aa8d5-c6b6-466a-81bb-fe8a67693cee&DataBase=10449_UNLFCSHThis paper provides an empirical analysis of the impact of regime changes in the composition and patterns of recruitment of the Portuguese ministerial elite throughout the last 150 years. The ‘out-of-type’, violent nature of most regime transformations accounts for the purges in and the extensive replacements of the political personnel, namely of the uppermost officeholders. In the case of Cabinet members, such discontinuities did not imply, however, radical changes in their social profile. Although there were some significant variations, a series of salient characteristics have persisted over time. The typical Portuguese minister is a male in his midforties, of middle-class origin and predominantly urban-born, highly educated and with a state servant background. The two main occupational contingents have been university professors - except for the First Republic (1910-26) - and the military, the latter having only recently been eclipsed with the consolidation of contemporary democracy. As regards career pathways, the most striking feature is the secular trend for the declining role of parliamentary experience, which the democratic regime did not clearly reverse. In this period, a technocratic background rather than political experience has been indeed the privileged credential for a significant proportion of minister

Bologna guidelines for diagnosis and management of adhesive small bowel obstruction (ASBO)

Background: Adhesive small bowel obstruction (ASBO) is a common surgical emergency, causing high morbidity and even some mortality. The adhesions causing such bowel obstructions are typically the footprints of previous abdominal surgical procedures. The present paper presents a revised version of the Bologna guidelines to evidence-based diagnosis and treatment of ASBO. The working group has added paragraphs on prevention of ASBO and special patient groups. Methods: The guideline was written under the auspices of the World Society of Emergency Surgery by the ASBO working group. A systematic literature search was performed prior to the update of the guidelines to identify relevant new papers on epidemiology, diagnosis, and treatment of ASBO. Literature was critically appraised according to an evidence-based guideline development method. Final recommendations were approved by the workgroup, taking into account the level of evidence of the conclusion. Recommendations: Adhesion formation might be reduced by minimally invasive surgical techniques and the use of adhesion barriers. Non-operative treatment is effective in most patients with ASBO. Contraindications for non-operative treatment include peritonitis, strangulation, and ischemia. When the adhesive etiology of obstruction is unsure, or when contraindications for non-operative management might be present, CT is the diagnostic technique of choice. The principles of non-operative treatment are nil per os, naso-gastric, or long-tube decompression, and intravenous supplementation with fluids and electrolytes. When operative treatment is required, a laparoscopic approach may be beneficial for selected cases of simple ASBO. Younger patients have a higher lifetime risk for recurrent ASBO and might therefore benefit from application of adhesion barriers as both primary and secondary prevention. Discussion: This guideline presents recommendations that can be used by surgeons who treat patients with ASBO. Scientific evidence for some aspects of ASBO management is scarce, in particular aspects relating to special patient groups. Results of a randomized trial of laparoscopic versus open surgery for ASBO are awaited

Resposta da produtividade de grãos e outras características agronômicas do trigo EMBRAPA-22 irrigado ao nitrogênio em cobertura

As doses e a época de aplicação do nitrogênio (N) podem influenciar as características agronômicas do trigo (Triticum aestivum L.) irrigado e, conseqüentemente, a produtividade de grãos. Neste sentido, foram instalados dois experimentos na Estação Experimental da Universidade Federal de Viçosa, localizada em Coimbra (MG), em 1995 e 1996. Os tratamentos foram constituídos pela combinação de quatro doses de N (30, 60, 90 e 120 kg ha-1), quatro formas de parcelamento (dose total aos 20 dias da emergência (DAE); ½ aos 20 + ½ aos 40 DAE; 1/3 aos 20 + 2/3 aos 40 DAE e 2/3 aos 20 + 1/3 aos 40 DAE) e uma testemunha (sem N em cobertura), dispostos em esquema fatorial 4 x 4 + 1, no delineamento em blocos casualizados com quatro repetições. A altura e o acamamento das plantas, a biomassa seca, o índice de colheita, a massa de mil grãos, o peso hectolítrico e a produtividade de grãos foram influenciados pelas doses de N. Em 1996, o número de espigas por metro quadrado e o número de perfilhos férteis por planta diminuíram, em conseqüência do acamamento precoce das plantas, enquanto o número de grãos por espiga e o número de grãos por metro quadrado aumentaram com o incremento nas doses de N. As formas de parcelamento influenciaram somente o acamamento das plantas

The satisfactory growth and development at 2 years of age of the INTERGROWTH-21st Fetal Growth Standards cohort support its appropriateness for constructing international standards.

BACKGROUND: The World Health Organization recommends that human growth should be monitored with the use of international standards. However, in obstetric practice, we continue to monitor fetal growth using numerous local charts or equations that are based on different populations for each body structure. Consistent with World Health Organization recommendations, the INTERGROWTH-21st Project has produced the first set of international standards to date pregnancies; to monitor fetal growth, estimated fetal weight, Doppler measures, and brain structures; to measure uterine growth, maternal nutrition, newborn infant size, and body composition; and to assess the postnatal growth of preterm babies. All these standards are based on the same healthy pregnancy cohort. Recognizing the importance of demonstrating that, postnatally, this cohort still adhered to the World Health Organization prescriptive approach, we followed their growth and development to the key milestone of 2 years of age. OBJECTIVE: The purpose of this study was to determine whether the babies in the INTERGROWTH-21st Project maintained optimal growth and development in childhood. STUDY DESIGN: In the Infant Follow-up Study of the INTERGROWTH-21st Project, we evaluated postnatal growth, nutrition, morbidity, and motor development up to 2 years of age in the children who contributed data to the construction of the international fetal growth, newborn infant size and body composition at birth, and preterm postnatal growth standards. Clinical care, feeding practices, anthropometric measures, and assessment of morbidity were standardized across study sites and documented at 1 and 2 years of age. Weight, length, and head circumference age- and sex-specific z-scores and percentiles and motor development milestones were estimated with the use of the World Health Organization Child Growth Standards and World Health Organization milestone distributions, respectively. For the preterm infants, corrected age was used. Variance components analysis was used to estimate the percentage variability among individuals within a study site compared with that among study sites. RESULTS: There were 3711 eligible singleton live births; 3042 children (82%) were evaluated at 2 years of age. There were no substantive differences between the included group and the lost-to-follow up group. Infant mortality rate was 3 per 1000; neonatal mortality rate was 1.6 per 1000. At the 2-year visit, the children included in the INTERGROWTH-21st Fetal Growth Standards were at the 49th percentile for length, 50th percentile for head circumference, and 58th percentile for weight of the World Health Organization Child Growth Standards. Similar results were seen for the preterm subgroup that was included in the INTERGROWTH-21st Preterm Postnatal Growth Standards. The cohort overlapped between the 3rd and 97th percentiles of the World Health Organization motor development milestones. We estimated that the variance among study sites explains only 5.5% of the total variability in the length of the children between birth and 2 years of age, although the variance among individuals within a study site explains 42.9% (ie, 8 times the amount explained by the variation among sites). An increase of 8.9 cm in adult height over mean parental height is estimated to occur in the cohort from low-middle income countries, provided that children continue to have adequate health, environmental, and nutritional conditions. CONCLUSION: The cohort enrolled in the INTERGROWTH-21st standards remained healthy with adequate growth and motor development up to 2 years of age, which supports its appropriateness for the construction of international fetal and preterm postnatal growth standards