Interleukin 1 mediated acceleration of type II collagen-induced arthritis: effects of anti-inflammatory or anti-arthritic drugs

We previously demonstrated that treatments with rIL-1 beta accelerated the onset and progression of CIA in mice. In the present study, it was observed that IL-1 also enhanced the development of CIA in rats. Like the mouse model, maximal incidence (80-100%) of arthritis occurred within 7 days after the first treatment with IL-1 in rats. Thus, the acceleration of CIA by IL-1 (IL-1 CIA) may be an improved model for the rapid screening of anti-inflammatory and/or anti-arthritic drugs. As a first step to determining the utility of the IL-1 CIA model as a drug screen, we examined the ability of various known anti-inflammatory and anti-arthritic drugs to modify the IL-1 mediated enhancement of CIA in both rats and mice. The results of these studies showed that when analyzed in the IL-1 CIA model, rats and mice exhibited differences in their responses to several of these drugs. For example, dexamethasone, cyclophosphamide, azathioprine, various non-steroidal anti-inflammatory drugs (NSAIDs) as well as methotrexate were found active in the IL-1 CIA of rats. By contrast, the NSAIDs were found to be less effective in suppressing the IL-1 accelerated disease in mice. In both rats and mice, cyclosporine A and several disease modifying anti-arthritic drugs failed to the prevent the development of CIA that was potentiated by IL-1. Thus, in the IL-1 CIA model NSAIDs appeared to be less active in mice than rats. In conclusion, because of the shorter latent period required for the development of arthritis in the IL-1 treated animals, the IL-1 accelerated CIA model in both mice and rats may be useful for screening anti-inflammatory or anti-arthritic compounds.     

Traumatic mediastinal lymphocele mimicking other thoracic injuries: case report.

Thoracic duct injury and chylothorax are rare consequences of blunt thoracic trauma. A contained mediastinal lymph collection (ie, lymphocele) is rarer still. The article describes a case of posttraumatic mediastinal widening resulting from a high-speed motor vehicle accident. During the patient's radiologic assessment aortic rupture, paraspinal hematoma, esophageal injury, mediastinal tumor, and pseudomeningocele were sought and subsequently excluded. At this point a traumatic lymphocele was suggested, and the diagnosis was confirmed by computed tomography-guided percutaneous needle aspiration. The anatomy and physiology of the thoracic duct are reviewed.     

The use of deep inspiration preceding the valsalva maneuver and rapid expiration in color doppler imaging of the lower extremity veins

Deep inspiration preceding Valsalva maneuver and rapid expiration immediately following it (DIVE) enhance venous blood flow on color Doppler flow imaging (CDI). The effect of DIVE was assessed in 115 consecutive lower extremity examinations. Of these, 95 or 115 (83%) had negative CDI sonograms, and 20 of 115 (17%) had partially (six of 115) or completely (14 of 115) occluding deep vein thrombosis. DIVE enhanced venous blood flow in 68% of the negative cases, resulting in transient venous distention, and/or more complete color filling, and/or greater spectral flow velocities. The 14 cases with completely occluding thrombi showed no response to DIVE. Six cases with partially occluding thrombi showed moderate to mild response to DIVE, with improved color delineation of the residual patent lumen around the thrombus. The authors conclude that DIVE facilitates deep venous CDI, especially when compression cannot be used to augment venous flow.     

Antibody to a synthetic oligopeptide in subjects at risk for human immunodeficiency virus infection.

Detection of antibodies to human immunodeficiency virus (HIV) by enzyme-linked immunosorbent assay (ELISA) is the accepted method to screen blood products at risk to transmit infection. The presence of antibodies to HIV in 565 serum specimens from 274 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex, symptomatic and asymptomatic subjects at risk for AIDS, and controls was determined with an ELISA that incorporates synthetic peptides (designated E32/E34) representing sequences in the envelope glycoprotein gp41. Of 105 specimens from patients with AIDS or AIDS-related complex, 3 specimens that were negative by commercially licensed ELISA and immunoblot test were similarly unreactive in the E32/E34 ELISA. For homosexual men with generalized lymphadenopathy, 186 specimens were positive by the E32/E34 ELISA and 63 specimens were negative. In comparison, with the licensed ELISA, 184 of these samples were positive and 65 samples were negative. The two samples that were positive in the E32/E34 ELISA but not the commercial kit were also positive by immunoblotting. Sequential sera from one individual who apparently underwent seroconversion according to the commercial assays were all positive by E32/E34 ELISA and immunoblotting. Thus, the ELISA with synthetic peptides is an extremely sensitive and specific test of antibody response to HIV and has not yet yielded a negative result with a Western blot (immunoblot)-confirmed antibody-positive serum.     

Autographa californica M nucleopolyhedrovirus ProV-CATH is activated during infected cell death

V-CATH, a cathepsin L-like cysteine protease encoded by the baculovirus Autographa californica M nucleopolyhedrovirus, has been shown to play an essential role in host liquefaction. Similar to cellular cathepsin L, V-CATH is synthesized as an inactive proenzyme and is activated by cleavage of the propeptide. Previous studies indicated that removal of the propeptide was rapid, occurring as soon as the protein could be detected by Western blot, 22 h postinfection. We found, however, that these results reflected artifactual processing of the proenzyme. When the protease inhibitor E-64 was used to prevent this aberration, we found that proV-CATH accumulated in infected cells and activation did not begin until the onset of cell death, at approximately 80 h postinfection. Western blot analysis of fractions of live and dead cells isolated by fluorescence-activated cell sorting revealed that mature V-CATH was found only in dead cells. The regulation of activation of proV-CATH, therefore, was quite different from that of cellular cathepsins. Acridine orange staining revealed that lysosome integrity was lost in dead cells, an occurrence that could lead to the activation of proV-CATH by lysosomal proteases.     

Role of mesenchymal-epithelial interactions in mammary gland development

The mammary gland is a hormone-target organ derived from epidermis and develops as a result of reciprocal mesenchymal-epithelial interactions. The induction of mammary differentiation from indifferent epidermal cells by mammary mesenchyme implies induction of the complement of hormone receptors characteristic of normal mammary epithelium in cells of the epidermis. Considering the facts that mammary epithelial differentiation is induced by mammary mesenchyme and that certain aspects of hormone response (androgen-induced mammary regression) are inextricably linked to mesenchymal-epithelial interactions, it is evident that the biology of the mammary gland arises from and is maintained via cell-cell interactions. As a corollary, perturbation of stromal-epithelial interactions in adulthood may play a role in mammary carcinogenesis and in turn may provide opportunities for differentiation therapy.