The Somatic Complaint List: validation of a self-report questionnaire assessing somatic complaints in children

OBJECTIVE: To evaluate the Somatic Complaint List (SCL) in children. METHOD: At T1, 365 fourth and 352 fifth graders completed the SCL, the Children's Somatization Inventory (CSI-C), and the Mood Questionnaire. Parents (n=564) completed the parental form of the CSI-C (CSI-P). Six months later, the stability of the SCL and the CSI-C was assessed. RESULTS: The psychometric properties and stability of the SCL were good. Correlations with the CSI-C, negative moods, and the CSI-P complaints supported the validity. Moreover, the SCL was more strongly associated with negative moods and with parental reports of children's somatic complaints than the CSI-C. CONCLUSION: The SCL is a suitable questionnaire for assessing somatic complaints in school-aged children.     

Protein kinase C-zeta mediates retinal degeneration in response to TNF

Tumor necrosis factor-alpha (TNF) has been implicated in retinal ganglion cells (RGC) degeneration in glaucoma. Atypical protein kinase C (PKC) zeta is involved in cell protection against various stresses. The aim of this study was to investigate the potential proapoptotic effects of intravitreal injections of TNF with or without PKCzeta specific inhibitor on the rat retina. TNF was injected in the vitreous of rat eyes alone or in combination with specific PKCzeta inhibitor. PKCzeta and NF-kappaB were studied by immunohistochemistry and western-blotting analysis on retina, and apoptosis quantified by the TUNEL assay. While low basal PKCzeta was observed in the control eyes, TNF induced intense expression of PKCzeta mostly in bipolar cells processes. PKCzeta staining became nuclear when TNF was coinjected with PKCzeta inhibitor. TNF alone did not induce apoptosis in the retina. Coinjection of the PKCzeta-specific inhibitor and TNF, however, induced apoptosis in the inner nuclear and ganglion cell layers. The PKCzeta-specific inhibitor unmasks retinal cells to TNF cytotoxicity showing a link between the proapoptotic effects of TNF and the antiapoptotic PKCzeta signaling pathway.     

DNA fragmentation is increased in non-GABAergic neurons in bipolar disorder but not in schizophrenia

Apoptosis is thought to contribute to neuronal loss in bipolar disorder and schizophrenia, although empiric evidence in support of this idea has been lacking. In this study, we investigated whether or not apoptosis is associated with GABAergic interneurons in the anterior cingulate cortex in schizophrenia (n=14) and bipolar disorder (n=14) when compared to normal controls (n=14). A double-labeling technique using the Klenow method of in situ end-labeling (ISEL) of single-stranded DNA breaks was combined with an in situ hybridization localization of mRNA for the 67 kDa isoform of glutamate decarboxylase (GAD67) and applied to the anterior cingulate cortex of 14 normal controls, 14 schizophrenics, and 14 patients with bipolar disorder matched for age and postmortem interval. An increase in Klenow-positive, GAD67-negative nuclei were observed in layer V/VI of patients with bipolar disorder, but not schizophrenics. Klenow-positive cells that were also positive for GAD67 mRNA did not show differences in either patient group. Conclusions: This is the first demonstration that there is more DNA fragmentation in cells showing no detectable GAD67 mRNA in patients with bipolar disorder than in schizophrenics or controls. These findings suggest that non-GABAergic cells may be selectively vulnerable to oxidative stress in patients with bipolar disorder.     

A direct effect of aldosterone on endothelin-1 gene expression in vivo

Aldosterone regulates sodium reabsorption in epithelial tissues such as the kidney and colon, via a pathway involving the activation of intracellular mineralocorticoid receptors (MR), induction of specific target genes, and a subsequent increase in sodium channel activity. Characterized aldosterone target genes in epithelia include the serum and glucocorticoid-regulated kinase 1 and the corticosteroid hormone-induced factor. Endothelin-1 (ET-1) is a potent vasoconstrictor that alters both sodium transport and hydrogen ion secretion in the kidney. Recent studies in a mouse medullary collecting duct cell line and rat A-10 smooth muscle cells have demonstrated an acute response of ET-1 gene expression to aldosterone. In the present study, we have investigated the ET-1 gene in vivo as a potential direct aldosterone-regulated target gene in the kidney and colon. Adrenalectomized rats given a single dose of aldosterone were found to have a 2-fold increase in ET-1 mRNA levels in the kidney and colon after 1 h. No significant changes in mRNA levels were detected for the related isoforms ET-2 or ET-3. Cotreatment with aldosterone and potassium canrenoate, a MR antagonist, blocked induction of ET-1 mRNA, suggesting that induction was mediated via the MR. In a time course study, ET-1 mRNA levels were induced rapidly by aldosterone, with levels of ET-1 mRNA maximally increased 2- and 2.5-fold after 1 h in the kidney and colon, respectively. These results suggest that ET-1 is a direct aldosterone gene target in the kidney and colon and may play an important role in aldosterone-regulated ion homeostasis.     

Long‐lasting cross‐presentation of tumor antigen in human DC

DC cross‐present exogenous antigens on MHC class I molecules, a process required for the onset of anti‐tumor immune responses. In order to study the cross‐presentation of tumor antigens by human DC, we compared the pathways of cross‐presentation of long peptides requiring internalization and intracellular processing with the direct presentation of short peptides, which does not require intracellular processing. We found that, after brief incubations with DC, short peptides were presented to CD8⁺ T cells with higher efficiencies than long peptides. After longer times of chase in the absence of peptide, however, the efficiency of presentation of the two types of peptides was reversed. After 2–3 days, DC pulsed with long peptides still activated T cells efficiently, while DC pulsed with short peptides failed to do so. Long‐lasting presentation of the long peptides was, at least in part, due to a stored persistent pool of antigen, which was still available for loading on MHC class I molecules after several days of chase. These results show that the use of long synthetic peptides allows the efficient, long‐lasting, presentation of tumor antigens, suggesting that long peptides represent an interesting approach for active anti‐tumor vaccination.