Bone mineral density in adolescent girls with early onset of anorexia nervosa.

BACKGROUND & AIMS: To assess prevalence of bone mineral density (BMD) reduction and relationship between bone mineral status and anthropometric assessment, nutritional intake and physical activity in adolescents with early anorexia nervosa (AN). METHODS: Fifty-seven consecutive AN patients and 57 healthy controls underwent anthropometric status, bone density, body composition and physical activity evaluations. In AN patients clinical features and nutritional intake were also assessed. RESULTS: Thirty-five patients with AN (62%) and 44 healthy subjects (77%) (pNS) showed normal BMD. Mean value of BMD Z-score was -0.6+/-0.9 in AN patients and -0.2+/-1.4 in controls (pNS). Weight at diagnosis and lean mass resulted the main predictor of bone loss but also height, best weight before diagnosis and BMI resulted correlated with bone mineral status in AN patients. Additionally, AN patients maintained good levels of protein intake and sport activity CONCLUSIONS: Early diagnosis may prevent bone loss in AN patients. Protein intake and moderate physical activity seem to be useful to maintain an adequate bone mineral status.

Clinical value of immunoglobulin A antitransglutaminase assay in the diagnosis of celiac disease.

OBJECTIVES: Our goal was to evaluate the possible correspondence between antitissue transglutaminase of immunoglobulin A class levels and stage of mucosal damage in patients affected by celiac disease. In addition, we assessed clinical use of antitissue transglutaminase values to predict biopsy results. METHODS: One thousand eight hundred eighty-six consecutive patients with symptoms suggestive of celiac disease and 305 healthy controls underwent determination of serum levels of immunoglobulin A and antitissue transglutaminase. An intestinal biopsy was performed in subjects with antitissue transglutaminase levels > or = 4 IU/mL and in subjects with negative antitissue transglutaminase levels but with clinical suspicion of celiac disease. Histologic grading of celiac disease was consistent with the Marsh classification. RESULTS: One hundred eighty-six subjects with positive antitissue transglutaminase levels and 91 patients with negative antitissue transglutaminase levels were submitted to biopsy. In all healthy subjects, antitissue transglutaminase results were negative. Histologic evaluations in patients with positive antitissue transglutaminase levels gave the following results: type 0 in 25 patients, type 1 in 3 patients, type 2 in 4 patients, type 3a in 22 patients, type 3b in 74 patients, and type 3c in 58 patients. None of the patients with negative antitissue transglutaminase levels showed histologic findings suggestive of celiac disease. The mean antitissue transglutaminase values in patients without mucosal atrophy were significantly lower than in patients with mucosal atrophy. Antitissue transglutaminase values > or = 20 IU/mL were found in only 1 patient without mucosal atrophy. CONCLUSIONS: Our study found a strong correspondence between antitissue transglutaminase levels and stage of mucosal injury; antitissue transglutaminase values > 20 IU/mL seemed to be strongly predictive of mucosal atrophy.

Duodenal stenosis, a new finding on congenital rubella syndrome: case description and literature review.

Congenital rubella syndrome (CRS) continues to represent a public healthcare problem although an effective vaccination program. Gastrointestinal involvement is rather infrequent and the association of CRS with duodenal stenosis has been never reported. In this study a case of CRS with duodenal diaphragm is reported and the gastrointestinal diseases described in association with CRS are reviewed. A 10-month-old child affected by CRS with congenital hearth disease, perceptive deafness and microcephaly, was admitted because of vomiting and failure to thrive. An upper endoscopy demonstrated dilated proximal duodenum and a perforated diaphragm in the second segment of the duodenum. Endoscopic membranectomy was therefore performed. Two months later the patient was submitted to a further endoscopic evaluation that showed a partial diaphragm persistence and a second excision was performed. Follow-up one year after the first treatment showed good clinical conditions, reasonable physical growth and disappearance of vomiting. In conclusion we report the first case of CRS in association with duodenal stenosis. Duodenal stenosis in the absence of other intestinal localizations may be due to rubella capacity of infecting only small numbers of fetal cells but we cannot exclude that the duodenal stenosis in our patient be only a casual association.

Notch3 and pre-TCR interaction unveils distinct NF-kappaB pathways in T-cell development and leukemia.

Notch signaling plays a critical role in T-cell differentiation and leukemogenesis. We previously demonstrated that, while pre-TCR is required for thymocytes proliferation and leukemogenesis, it is dispensable for thymocyte differentiation in Notch3-transgenic mice. Notch3-transgenic premalignant thymocytes and T lymphoma cells overexpress pTalpha/pre-TCR and display constitutive activation of NF-kappaB, providing survival signals for immature thymocytes. We provide genetic and biochemical evidence that Notch3 triggers multiple NF-kappaB activation pathways. A pre-TCR-dependent pathway preferentially activates NF-kappaB via IKKbeta/IKKalpha/NIK complex, resulting in p50/p65 heterodimer nuclear entry and recruitment onto promoters of Cyclin D1, Bcl2-A1 and IL7-receptor-alpha genes. In contrast, upon pTalpha deletion, Notch3 binds IKKalpha and maintains NF-kappaB activation through an alternative pathway, depending on an NIK-independent IKKalpha homodimer activity. The consequent NF-kappaB2/p100 processing allows nuclear translocation of p52/RelB heterodimers, which only trigger transcription from Bcl2-A1 and IL7-receptor-alpha genes. Our data suggest that a finely tuned interplay between Notch3 and pre-TCR pathways converges on regulation of NF-kappaB activity, leading to differential NF-kappaB subunit dimerization that regulates distinct gene clusters involved in either cell differentiation or proliferation/leukemogenesis.

PKC theta mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia.

Protein kinase (PK)C theta is a critical regulator of mature T-cell activation and proliferation, being implicated in TCR-triggered nuclear factor (NF)-kappa B activation and providing important survival signals to leukemic T cells. We previously showed that overexpression of pT alpha/pre-TCR and constitutive activation of NF-kappa B characterize the T-cell leukemia/lymphoma developing in Notch3-IC transgenic mice. We report here that PKC theta is a downstream target of Notch3 signaling and that its activation and membrane translocation require a functional pre-TCR in order to trigger NF-kappa B activation in thymocytes and lymphoma cells of transgenic mice. Furthermore, deletion of PKC theta in Notch3-IC transgenic mice reduces the incidence of leukemia, correlating with decreased NF-kappa B activation. This paper therefore suggests that PKC theta mediates the activation of NF-kappa B by pre-TCR in immature thymocytes and contributes to the development of Notch3-dependent T-cell lymphoma.

Experimental parkinsonism modulates multiple genes involved in the transduction of dopaminergic signals in the striatum.

The irreversible loss of the dopamine-mediated control of striatal function is considered the functional substrate of the motor symptoms of Parkinson's disease. This pathological event causes a complex rearrangement of neuronal activity which involves specific dopamine-regulated cellular functions and, secondarily, several other cellular properties and transmitter systems. In the present study, we applied recently developed cDNA microarray technology to investigate the genetic correlates of the alterations produced by 6-hydroxydopamine-induced dopamine denervation in the nucleus striatum. We found that chronic dopamine denervation caused the modulation of 50 different genes involved in several cellular functions. In particular, products of the genes modulated by this experimental manipulation are involved both in the intracellular transduction of dopamine signal and in the regulation of glutamate transmission in striatal neurons, providing some information on the possible neuronal events which lead to the reorganization of glutamate transmission in the striatum of parkinsonian rats.