Developmental reprogramming of rat GLUT5 requires glucocorticoid receptor translocation to the nucleus

Fructose consumption has increased dramatically but little is known about mechanisms regulating the intestinal fructose transporter GLUT5 in vivo . In neonatal rats, GLUT5 can be induced only by luminal fructose and only after 14 days of age, unless the gut is primed with dexamethasone prior to fructose perfusion. To elucidate the mechanisms underlying dexamethasone modulation of GLUT5 development, we first identified the receptor mediating its effects then determined whether those effects were genomic. The glucocorticoid receptor (GR) antagonist RU486 dose-dependently prevented the dexamethasone-mediated effects on body weight, intestinal arginase2 (a known GR-regulated gene) and GLUT5. In contrast, an antagonist of the mineralocorticoid receptor as well as agonists of progesterone (PR) and pregnane-X (PXR) receptors did not block the effects of dexamethasone. These receptor antagonists and agonists had no effect on the intestinal glucose transporter SGLT1. Translocation of the GR into the enterocyte nucleus occurred only in dexamethasone-injected pups perfused with fructose, was accompanied by marked increases in brush border GLUT5 abundance, and was blocked by RU486. A priming duration of ∼24 h is optimal for induction but actinomycin D injection before dexamethasone priming prevented dexamethasone from allowing luminal fructose to induce GLUT5. Actinomycin D had no effect on dexamethasone-independent fructose-induced increases in glucose-6-phosphatase mRNA abundance, suggesting that it did not prevent fructose-induction of GLUT5, but instead prevented dexamethasone-induced synthesis of an intermediate required by fructose for GLUT5 regulation. In suckling rats < 14 days old, developmental regulation of transporters may involve cross-talk between hormonal signals modulating intestinal maturation and nutrient signals regulating specific transporters.     

Pulmonary and mediastinal "sarcoidosis" following surgical resection of cancer

Previous reports indicate that enlarged hilar and mediastinal lymph nodes caused by sarcoid-like reactions may develop after curative resection of cancer, and their presence does not necessarily denote neoplastic recurrence. Reports further suggest that coexisting pulmonary infiltrates in this setting may be related to sarcoidosis. In this study, we describe two patients who had resected lung and gastric cancer and who later developed pulmonary interstitial infiltrate, concurrent with progressive mediastinal lymphadenopathy initially thought to be caused by intrathoracic dissemination of their cancer. These changes were shown by open lung biopsy to be a benign, granulomatous reaction interpreted as sarcoidosis. Thus, it is important to recognize this clinical pattern when pulmonary infiltrates develop after complete treatment of cancer in an otherwise relapse-free patient and to encourage lung or lymph node biopsy in these particular settings in order to confirm a sarcoid-like reaction, thereby avoiding unnecessary chemotherapy for presumed tumor recurrence.     

p14ARF protein expression is a predictor of both relapse and survival in squamous cell carcinoma of the anterior tongue.

PURPOSE: The INK4A-ARF locus at chromosome 9p21 is frequently altered in head and neck squamous cell carcinoma (SCC) and encodes two distinct tumor suppressors, p16(INK4A) and p14(ARF). This study addressed the role of p14(ARF) as a potential prognostic marker in this disease. EXPERIMENTAL DESIGN: p14(ARF) protein expression was assessed by immunohistochemistry in a cohort of 140 patients with SCC of the anterior tongue. Using univariate and multivariate Cox's proportional hazards models, the outcomes examined were time to disease recurrence or death, with or without clinicopathologic covariates, including nodal status, disease stage, treatment status, Ki-67 staining, and molecular markers with known functional or genetic relationships with p14(ARF) (p16(INK4A), p53, pRb, p21(WAF1/CIP1), E2F-1). RESULTS: On multivariate analysis, p14(ARF) positivity (nucleolar p14(ARF) staining and/or nuclear p14(ARF) staining in >/=30% of tumor cells) was an independent predictor of improved disease-free survival (DFS; P = 0.002) and overall survival (OS; P = 0.002). This was further enhanced when p14(ARF) positivity was cosegregated with positive (>/=1%) p16(INK4A) staining (DFS, P < 0.001; OS, P < 0.001). Patients whose cancers were p14(ARF) negative and p53 positive (>50%) had the poorest outcome (DFS, P < 0.001; OS, P < 0.001) of any patient subgroup analyzed. CONCLUSIONS: These data show that in patients with SCC of the tongue, combined nuclear and nucleolar expression of p14(ARF) protein predicts for improved DFS and OS independent of established prognostic markers.     

Physical measures and biomarker collection in health surveys: Propensity to participate

Population-based surveys have long been a key tool for health researchers, policy makers and program managers. The addition of bio-measures, including physical measures and specimen collection, to self-reported health and health behaviors can increase the value of the research for health sciences. At the same time, these bio-measures are likely to increase the perceived burden and intrusiveness to the respondent. Relatively little research has been reported on respondent willingness to participate in surveys that involve physical measures and specimen collection and whether there is any associated non-response bias.This paper explores the willingness of respondents to participate in surveys that involve physical measures and biomarkers. A Census-balanced sample of nearly 2000 adults from a national mobile panel of persons residing in the U.S. were interviewed. Willingness to participate in six specific bio-measures was assessed. The survey finds a high correlation in the willingness of respondents to participate among these specific bio-measures. This suggests there is a general propensity towards (and against) bio-measures among potential respondents, despite some differences in willingness to participate in the more sensitive, intrusive or burdensome biomarkers. This study finds the general propensity to participate in bio-measures is correlated with a number of key measures of health and illness. This suggests that the inclusion of biomarkers in health surveys may introduce some bias in key measures that need to be balanced against the value of the additional information.     

The light bulb sign in pheochromocytoma

Abdominal Radiology -     

Predictors of early relapse among adolescent crack users

Relapse is associated with a poor prognosis among drug users. Crack cocaine users are more prone to severe dependence because of the intensity of use. Additionally, initiating drug use during adolescence worsens users' prognosis due to the increased rates of impulsivity and other risk behaviors. This study aimed to identify the predictors of early relapse among adolescent crack users discharged from inpatient treatment. A cohort study was conducted with 89 psychiatric inpatients aged 12–17 years from two different hospitals in southern Brazil who met the criteria for crack abuse or dependence. Demographic data, substance use disorders, psychiatric comorbidities, and crack consumption profile were assessed during hospitalization using the Teen Addiction Severity Index, Schedule for Affective Disorders and Schizophrenia for School Age Children—Present and Lifetime, and Crack Consumption Profile. Participants were re-assessed at 1 and 3 months after hospital discharge to determine their crack cocaine use based on self-report, family/caregiver information, and urine tests, whenever possible. There were extremely high rates of relapse (valid percent) in the first and third months, 65.9 and 86.4%, respectively. Statistically significant associations were observed between relapse in the first month and length of cocaine/crack cocaine use, and length of hospital stay. Data at 3 months were not analyzed because of the small number of patients who did not relapse. The high rates and significant associations found in this study suggest that intensive outpatient treatment strategies targeting this population should be developed and implemented to prevent early relapse after detoxification. One of the possible approaches, based on recent studies, might explore motivation as a strategy to reduce the rate of early relapse.