Pulmonary disease during the treatment of rheumatoid arthritis with low dose pulse methotrexate

Methotrexate therapy has been effective in the treatment of RA with short term experience suggesting little serious adverse reactions. Our review of 168 patients receiving methotrexate has identified nine patients with probable or possible methotrexate-induced pulmonary toxicity, giving a prevalence of 5% and an incidence of 3.9 per 100 patients per year. No clinical or laboratory features showed an association that could potentially predict the development of pulmonary disease. All patients experienced complete recovery with supportive care and/or corticosteroid therapy. Clinical monitoring for this complication is warranted in all patients receiving long term methotrexate therapy for RA.     

Reduced expression of AP27 protein, the product of a growth factor-repressible gene, is associated with diminished adipocyte differentiation.

We have recently characterized an adipocyte cDNA (clone 5) that is enhanced in expression by environmental and hormonal conditions favoring adipogenic differentiation. Moreover, certain agents including fibroblast growth factor and phorbol 12-myristate 13-acetate (but not epidermal growth factor) markedly inhibit clone 5 gene expression and prevent TA1 cell differentiation. These results led us to propose that a threshold level of the clone 5 gene product (AP27 protein) is required for triggering adipocyte differentiation. We have constructed vectors that direct the synthesis of clone 5 antisense RNA to reduce the levels of AP27 in adipogenic cell lines TA1 and 3T3-L1. We show here that when these cells express clone 5 antisense RNA, they fail to undergo morphological differentiation, whereas adipogenesis is unaffected in cells expressing antisense beta-actin or ferritin heavy-chain RNA. We further show that cells expressing clone 5 antisense RNA (but not the other antisense RNAs) are unable to induce the expression of characteristic "adipocyte-specific" mRNAs. The level of inhibition of differentiation by clone 5 antisense RNA correlates with decreased levels of AP27 protein. These results provide strong evidence that expression of AP27 is linked to adipogenic differentiation and that AP27 may be a component of an as-yet-uncharacterized signal-transduction pathway required for the triggering of adipocyte differentiation.     

Antibodies to DNP, DNP—glycylglycylglycine and DNP—p-aminobenzoylglutamate

The antibodies to a series of three dinitrophenyl (DNP) derivatives of increasing site-filling capacity (DNP; DNP—glycylglycylglycine and DNP—p-aminobenzolylglutamate) have been isolated in order to assess the effect of the molecular dimensions of a haptenic group on the diversity of the immune response. A decrease in both the intensity and first appearance of precipitable antibody associated with an increase in molecular size of the hapten was observed. In a 5-week interval, the affinity constant for the homologous hapten of anti-DNP—BGG antibody increased approximately 100-fold. In the same interval, the affinity of anti-DNP—glycylglycylglycine—BGG antibodies changed only three- to four-fold and no change in the affinity constant was observed for the anti-DNP—p-aminobenzolyglutamate—BGG antibodies. There were no significant differences in the structural heterogeneity of the antibodies to the three haptens as measured by micro-isoelectric focusing. These observations suggest that temporal variations in binding affinity decreases as the site-filling capacity of the antigeneic determinant increases, thereby restricting the number of ways the determinant can orient itself in the combining site. It would appear that variations in antibody affinity are not indicative of antibody structural heterogeneity.     

Physiological response and childhood anxiety: association with symptoms of anxiety disorders and cognitive bias.

This study examined the physiological response (skin conductance and heart rate [HR]) of youth exposed to a mildly phobic stimulus (video of a large dog) and its relation to child- and parent-reported anxiety symptoms and cognitive bias in a community-recruited sample of youth (n = 49). The results of this study indicated that HR and skin-conductance response were associated with youth report but not parent report of their child's symptoms of anxiety disorders and that HR response was more strongly associated with anxiety symptoms than skin-conductance response. Physiological response was uniquely associated with youth-reported symptoms of anxiety rather than youth-reported depression. Finally, HR response interacted with cognitive bias in predicting childhood anxiety disorder symptoms in a manner consistent with theories of the etiology of anxiety disorders.