Depression: a common but underrecognized condition associated with end-stage renal disease

We describe a patient with end-stage renal disease (ESRD) who developed depression over the period of dialysis initiation. Depression is an extremely common but underrecognized disorder in the dialysis population, which is one of the rationales for this case report. Here we present the epidemiology, mechanisms for diagnosis, associations with medical morbidity, and treatment modalities specifically for patients on dialysis.     

Children grow and horses race: is the adiposity rebound a critical period for later obesity?

Background  

The adiposity rebound is the second rise in body mass index that occurs between 3 and 7 years. An early age at adiposity rebound is known to be a risk factor for later obesity. The aim here is to clarify the connection between the age at rebound and the corresponding pattern of body mass index change, in centile terms, so as to better understand its ability to predict later fatness.     

Ras modulates Myc activity to repress thrombospondin-1 expression and increase tumor angiogenesis

Tumor angiogenesis is postulated to be regulated by the balance between pro- and anti-angiogenic factors. We demonstrate that the critical step in establishing the angiogenic capability of human cells is the repression of the critical anti-angiogenic factor, thrombospondin-1 (Tsp-1). This repression is essential for tumor formation by mammary epithelial cells and kidney cells engineered to express SV40 early region proteins, hTERT, and H-RasV12. We have uncovered the signaling pathway leading from Ras to Tsp-1 repression. Ras induces the sequential activation of PI3 kinase, Rho, and ROCK, leading to activation of Myc through phosphorylation; phosphorylation of Myc via this mechanism enables it to repress Tsp-1 expression. We thus describe a novel mechanism by which the cooperative activity of the oncogenes, ras and myc, leads directly to angiogenesis and tumor formation.     

A study of the immunosuppressive properties of Sch 24937

Sch 24937 (6-bromo-5-chloro-2-1[(methylsulfonyl) acetyl] 3-(2-pyridyl indole) was previously shown to be an immunosuppressant with potent inhibitory effects on B lymphocyte mediated immune responses. The present investigation was primarily designed to compare the immunopharmacological profile of Sch 24937 with that of cyclosporin A (CSA) a well-known immunosuppressive drug that has selective effects on T-lymphocyte-mediated immune responses. The results show that while the immunosuppressive activity of CSA in vitro is superior to that of Sch 24937, in general the latter agent is a more potent inhibitor of immune responses in vivo. The activity of Sch 24937 in rat models of adjuvant arthritis and experimental allergic encephalomyelitis is also described. While Sch 24937 exhibits the type of immunopharmacological profile that is likely to yield a good therapeutic effect in the treatment of immune-mediated chronic inflammatory diseases, hepatotoxicity associated with the compound precludes its development for the treatment of non-life threatening human autoimmune conditions.     

MR imaging of facial nerve enhancement in Bell palsy or after temporal bone surgery

The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding.     

A study of adaptive responses in cell signaling in migraine and cluster headache: correlations between headache type and changes in gene expression

The project was an investigation into whether changes in the expression of G-proteins underlie altered cell signaling in migraine and cluster headache. The basis for this assumption is that altered physiological responses are seen in migraineurs and that differences in cell signaling are detected biochemically in various cell types isolated from peripheral blood. Levels of three G-protein mRNAs—Gsα, Giα, and Gqα were quantified in lymphocytes from clinically well-defined migraine and cluster headache patients and correlated with headache type and influence of drug treatment. Giα mRNA was reduced by 50% in all migraine patients compared with control subjects; similarly in patients with or without aura, in patients with a migraine headache at the time of sampling, and patients in a quiescent state. No reduction in the levels of Gsα or Gqα mRNA were seen in migraine patients. A smaller reduction was seen in cluster headache patients, most marked in those without medication. Levels of Gsα. mRNA were significantly reduced in cluster headache patients compared with migraine patients. The marked down-regulation of Giα mRNA in migraine, whether quiescent or acute, indicates either an adaptive response to headache in this group of patients or that low levels of Giα mRNA make individuals more susceptible to migraine.