TGFbeta signaling is initiated when the type I receptor phosphorylates the MAD-related protein, Smad2, on C-terminal serine residues. This leads to Smad2 association with Smad4, translocation to the nucleus, and regulation of transcriptional responses. Here we demonstrate that Smad7 is an inhibitor of TGFbeta signaling. Smad7 prevents TGFbeta-dependent formation of Smad2/Smad4 complexes and inhibits the nuclear accumulation of Smad2. Smad7 interacts stably with the activated TGFbeta type I receptor, thereby blocking the association, phosphorylation, and activation of Smad2. Furthermore, mutations in Smad7 that interfere with receptor binding disrupt its inhibitory activity. These studies thus define a novel function for MAD-related proteins as intracellular antagonists of the type I kinase domain of TGFbeta family receptors.

No abstract

This preliminary investigation has shown limbic blood flow increase with IPT yet not venlafaxine, while both treatments demonstrated increased basal ganglia blood flow. This was, however, a short trial with a small sample, no control group, and different symptom reduction in the 2 groups.

A cDNA, cRKIN1, encoding a putative homologue of the yeast (Saccharomyces cerevisuiae) SNFl (6), human cells (7), and Xenopus (8) are also present in pea (9) and Arabidopsis (10). All protein kinases that have been characterized in detail contain a number of key residues and conserved regions in the catalytic domain (11) but can be divided into two classes: those that phosphorylate serine/threonine residues and those that phosphorylate tyrosine residues. In the present report, we present the nucleotide sequence of a cDNA, cRKIN1,** isolated from a rye endosperm cDNA library. The cRKIN1-encoded protein contains all the invariant residues and conserved domains characteristic ofeukaryotic protein-serine/threonine kinases. It is particularly similar to the product ofthe SNFJ gene of yeast (Saccharomyces cerevisiae) (12), a protein affecting global regulation of carbon metabolism, and the expression of cRKIN1 in yeast snfl mutants restores SNFJ function.

No abstract

Identifying lower respiratory pathogens in young, non expectorating cystic fibrosis (CF) patients has been problematic. Bronchial secretions are difficult to obtain, and little is known about lower airway flora in these patients. We collected simultaneous bronchial and oropharyngeal specimens in 43 CF patients in optimal respiratory status, including both expectorating (17) and nonexpectorating (26) patients, to determine the predictive value of oropharyngeal cultures for identifying lower airway pathogens. An additional goal was to characterize the lower respiratory flora of these patients. Predictive values were defined as the proportion of oropharyngeal culture results that accurately reflected the results of bronchial cultures. Predictive values of positive oropharyngeal cultures in nonexpectorating patients were 83% (95% confidence interval 36 to 100%) for Pseudomonas aeruginosa and 91% (59 to 100%) for Staphylococcus aureus. Predictive values of negative oropharyngeal cultures were lower: 70% (48 to 86%) for R aeruginosa and 80% (52 to 96%) for S. aureus. A relatively high proportion of nonexpectorating CF patients less than 10 yr old had R aerusginosa (11 of 24, 46%) or Klebsiella species (5 of 24, 21%) in their lower airways. The isolation of Klebsiella was associated with younger age (p = 0.03) and recent administration of antistaphylococcal antibiotics (p = 0.05). Our results suggest that oropharyngeal cultures yielding R aeruginosa or S. aureus are highly predictive, but such cultures lacking these organisms do not rule out the presence of these pathogens in the lower airways of CF patients.

No abstract

Previous research has been inconsistent in documenting a strong relationship between depression and HIV/AIDS, although a recent meta-analysis of studies examining this issue indicates that rates of depression are modestly higher for this population. For the current study, conducted from 2001-2004, we sought to examine rates and types of depressive symptoms in a cohort of patients receiving HIV care at two urban medical centers. These patients were participants in an intervention study examining adherence and mental health in persons triply diagnosed with psychiatric disorders, substance use disorders, and HIV/AIDS. Nearly three quarters of these participants were people of color, two thirds described their sexual orientation as heterosexual, and the vast majority were unemployed. We sought to examine the relationship of depression to patients' adherence to antiretroviral medication regimens (highly active antiretroviral therapy [HAART]). Results obtained from structured clinical interviews and self-report questionnaires indicated that study participants experienced high rates of depressive symptoms, and that 72.9% of participants met criteria for major depressive disorder (MDD). The results of this study offer a detailed view of the incidence and nature of MDDs and depressive symptoms for an urban sample of substance-abusing adults with HIV/AIDS. Given the degree to which depressive symptoms and MDD appear to be prevalent for this group, as well as the observation that these symptoms are amenable to treatment, future research should focus on identifying helpful strategies and interventions for treating these symptoms, effective ways of providing linkages to care, and ways in which standardized assessment and treatment protocols might be adapted to better suit this population.