Reflex sympathetic dystrophy: diagnostic controversies.

Reflex sympathetic dystrophy, (RSD) is a complex physiologic response of the body to an external stimulus resulting in sympathetically mediated, usually nonanatomic pain, which is out of proportion to the inciting event or expected healing response. This complex entity has been the focus of much investigation, leading however to somewhat confusing and conflicting results and theories about the etiology and pathophysiology. There is even significant conflict about what characteristics define the clinical entity called RSD, and if these characteristics vary with the specific site of involvement. We have examined the current literature regarding these fundamental conflicts, and in addition we have evaluated the current controversies surrounding the role of Three Phase Radionuclide Bone Imaging (TPBI) for diagnosis, prognosis, and patient management. These controversies include the role of scintigraphy, the various criteria for scintigraphic diagnosis, and the reported variations in sensitivity and specificity of TPBI in RSD. We have examined several factors that may have affected these results, and potentially underestimated the value of scintigraphy in the diagnosis of RSD. In addition to the heterogeneous patient populations used to establish the diagnosis by different subspecialty physicians, these factors include duration of patient's symptoms, age of the patient population evaluated, location of the disease, and the varying scintigraphic scan interpretation criteria used.

Angiopeptin, the octapeptide analogue of somatostatin, decreases rat heart endothelial cell adhesiveness for mononuclear cells.

The effect of angiopeptin, a stable analogue of somatostatin, was studied on basal and interleukin-1-beta-induced endothelial cell adhesiveness for mononuclear cells, and compared to the effect of somatostatin. Angiopeptin and somatostatin decreased basal and interleukin-1-beta-induced endothelial cell adhesiveness for mononuclear cells. The decreased mononuclear cells adhesion to endothelial cells exposed to angiopeptin and somatostatin is not due to modulation of the expression of intrecellular adhesion molecule-1 because neither angiopeptin nor somatostatin decreased basal and interleukin-1-beta-induced expression of this adhesion molecule. The effect of angiopeptin in inhibiting endothelial cell adhesiveness for mononuclear cells was abolished by addition of dibutyryl-cyclic AMP. Angiopeptin induced a transient decrease in basal and interleukin-1-beta-induced cyclic AMP levels in endothelial cells. Exposure of unstimulated and interleukin-1-beta-activated endothelial cells to KT5720, a specific inhibitor of cyclic AMP-dependent protein kinase, decreased endothelial cell adhesiveness for mononuclear cells. Thus, angiopeptin most likely diminishes endothelial adhesiveness for mononuclear cells by affecting the cyclic AMP-dependent protein kinase signal transduction pathway. The findings suggest that angiopeptin and somatostatin may modify the development of the immune response by attenuating endothelial cell adhesiveness for mononuclear cells. Angiopeptin may have a potential clinical application as a modulator of some aspects of the immune response due to its long half-life and prolonged inhibitory effect on interleukin-1-beta induced endothelial adhesiveness for mononuclear cells.

Mapping and topographic localization of epitopes of the Yersinia pseudotuberculosis invasin protein.

The Yersinia pseudotuberculosis invasin protein is a 986-amino-acid outer membrane protein that promotes bacterial penetration into mammalian cells by binding to beta 1-chain integrin receptors. We previously showed that the integrin binding domain is encoded by the carboxyl-terminal 192 amino acids. To further investigate the structure of this protein, we characterized a set of 32 monoclonal antibodies (MAbs) directed against invasin. Invasin deletion derivatives and fusion proteins carrying different segments of invasin were used to map the epitopes of this set of MAbs into 10 overlapping but distinct intervals. Indirect immunofluorescence of intact bacteria expressing invasin demonstrated that two large regions of invasin contain epitopes exposed on the bacterial surface. To assess the role of these surface-exposed regions in the binding and invasion of mammalian cells, each of the MAbs was tested for its ability to inhibit these processes. All of the MAbs that recognized bacterial surface-exposed epitopes in the cell binding domain of invasin inhibited both cell attachment and cell penetration, and no other MAbs inhibited either activity.

Identification of the integrin binding domain of the Yersinia pseudotuberculosis invasin protein.

The invasin protein of the pathogenic Yersinia pseudotuberculosis mediates entry of the bacterium into cultured mammalian cells by binding several beta 1 chain integrins. In this study, we identified the region of invasin responsible for cell recognition. Thirty-two monoclonal antibodies directed against invasin were isolated, and of those, six blocked cell attachment to invasin. These six antibodies recognized epitopes within the last 192 amino acids of invasin. Deletion mutants of invasin and maltose-binding protein (MBP)--invasin fusion proteins were generated and tested for cell attachment. All of the invasin derivatives that carried the carboxyl-terminal 192 amino acids retained cell binding activity. One carboxyl-terminal invasin fragment and seven MBP--invasin fusion proteins were purified. The purified derivatives that retained binding activity inhibited bacterial entry into cultured mammalian cells. These results indicated that the carboxyl-terminal 192 amino acids of invasin contains the integrin-binding domain, even though this region does not contain the tripeptide sequence Arg-Gly-Asp.