p19Arf induces p53-dependent apoptosis during Abelson virus-mediated pre-B cell transformation

The Ink4a/Arf locus encodes p16^Ink4a and p19^Arf and is among the most frequently mutated tumor suppressor loci in human cancer. In mice, many of these effects appear to be mediated by interactions between p19^Arf and the p53 tumor-suppressor protein. Because Tp53 mutations are a common feature of the multistep pre-B cell transformation process mediated by Abelson murine leukemia virus (Ab-MLV), we examined the possibility that proteins encoded by the Ink4a/Arf locus also play a role in Abelson virus transformation. Analyses of primary transformants revealed that both p16^Ink4a and p19^Arf are expressed in many of the cells as they emerge from the apoptotic crisis that characterizes the transformation process. Analyses of primary transformants from Ink4a/Arf null mice revealed that these cells bypassed crisis. Because expression of p19^Arf but not p16 ^Ink4a induced apoptosis in Ab-MLV-transformed pre-B cells, p19^Arf appears to be responsible for these events. Consistent with the link between p19^Arf and p53, Ink4a/Arf expression correlates with or precedes the emergence of cells expressing mutant p53. These data demonstrate that p19^Arf is an important part of the cellular defense mounted against transforming signals from the Abl oncoprotein and provide direct evidence that the p19^Arf–p53 regulatory loop plays an important role in lymphoma induction.     

Annual risk of tuberculous infection in four defined zones of India: a comparative picture.

SETTING: Twenty-six selected districts in India. OBJECTIVES: To estimate the average annual risk of tuberculous infection (ARTI) in four defined zones in the country. STUDY DESIGN: A tuberculin survey was conducted in selected clusters of 26 districts in four defined zones of India. Children 1-9 years of age were subjected to tuberculin testing with ITU PPD RT23 with Tween 80, and the maximum transverse diameter of induration was measured 72 h later. Prevalence of infection was estimated using the cut-off point method (Method I) and the mirror-image technique (Method II) among children without bacille Calmette-Guérin scar. Results from individual zones have been reported earlier, and the results from all four zones are presented here as a consolidated summary. RESULTS: The ARTI computed from estimated prevalence was found to be lowest in the southern zone (Method I: 1.1%, Method II: 1.0%). It was higher in the eastern zone (1.3% by both methods) and highest in the western (Method I: 1.8%, Method II: 1.6%) and northern zones (1.9% by both methods). The proportion of infected children was found to be significantly higher in urban than in rural areas in all zones. CONCLUSION: The intensified tuberculosis control efforts need to be sustained for many years.     

Adiponectin levels are high in children with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency

Objective: It has been shown that adiponectin serves as an insulin-sensitizing adipokine. Serum concentrations of adiponectin are low in children with obesity, and increase with fat mass loss, indicating that adiponectin can serve as a biomarker. Since the prevalence of overweight and obesity is increased in children with congenital adrenal hyperplasia (CAH), our study aimed to evaluate serum levels of adiponectin in a cohort of CAH children and adolescents, and their associations with clinical parameters such as chronological age (CA), body mass index (BMI), Tanner stage (TS), medication and metabolic control.
Patients and methods: We studied 51 patients, aged between 5.6 and 19.6 years (median 11.8; 30 females, 21 males), cross-sectionally. All patients had genetically confirmed CAH and received standard steroid substitution therapy. Adiponectin was measured by an enzyme linked immunoassay. Since BMI SDS of the CAH cohort were significantly higher compared to the reference population, we built matched pairs with healthy Caucasian subjects from a normal representative cohort for sex, Tanner stage, chronologic age and BMI.
Results: Adiponectin concentrations were significantly higher in CAH patients (median 11 μg/L) compared to the matched controls (6.7 μg/L, p < 0.0001). Correlation analyses in CAH patients revealed a significant inverse relationship between adiponectin and CA, TS, BMI, serum DHEAS and serum testosterone, but no correlation with hydrocortisone and fludrocortisone dosage.
Conclusion: Currently, the importance of the elevated adiponectin concentrations in CAH children for risk assessment is not clear. However, our data imply that besides adequate metabolic control of glucocorticoid substitution, a long-term follow-up of other metabolic markers of insulin resistance should be conducted in CAH patients.