Damage accrual in systemic lupus erythematosus in Dominicans in New York City and the Dominican Republic.

Objectives Hispanics with systemic lupus erythematosus (SLE) in the United States have more severe disease and damage accrual compared with whites. Data on Hispanics of similar ancestry in geographically different locations is limited but essential in defining genetic and environmental factors for SLE. This study evaluates SLE disease burden in two Dominican communities, Washington Heights in New York City (NYC) and Santiago in the Dominican Republic (DR). Methods Disease activity (SLE Disease Activity Index 2000 (SLEDAI-2K)) and damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)) were cross-sectionally measured in 76 Dominican SLE patients from the Columbia University Lupus Cohort in NYC and compared with 75 Dominican SLE patients living in Santiago in the DR. Results Mean (±SD) age was 40 (±14) and 36 (±11) years for NYC and DR patients, respectively. Median disease duration was 8 years. Disease activity was mild in both groups (SLEDAI-2K of 3 in NYC versus 4 in the DR). NYC Dominicans had more discoid lesions, positive anti-dsDNA, and anti-SSB antibodies. Dominicans in the DR used more corticosteroids, had less medical insurance, lower educational level, and were more likely to be unemployed, whereas more Dominicans in NYC smoked. NYC patients had a higher SDI compared with SLE patients in the DR (0.96 versus 0.24, p < 0.0001). Statistical significance was maintained in adjusted analysis (1.26 versus 0.57, p < 0.0001). Conclusion SLE Dominican patients in NYC had a higher SDI than those in the DR. Longitudinal studies are needed to ascertain whether this difference is due to biological, environmental factors, immigration patterns or a survival bias.

Allosteric modulation of protease-activated receptor signaling.

The protease-activated receptors (PARs) are G protein-coupled receptors (GPCRs) that are uniquely activated by proteolysis. PARs mediate hemostasis, thrombosis, inflammation, embryonic development and progression of certain malignant cancers. The family of PARs include four members: PAR1, PAR2, PAR3 and PAR4. PARs harbor a cryptic ligand sequence within their N-terminus that is exposed following proteolytic cleavage. The newly formed PAR Nterminus functions as a tethered ligand that binds intramolecularly to the receptor to trigger transmembrane signaling. This unique mechanism of activation would indicate that regardless of the activating protease, cleavage of PARs would unmask a tethered ligand sequence that would induce a similar active receptor conformation and signaling response. However, this is not the case. Recent studies demonstrate that PARs can be differentially activated by synthetic peptide agonists, proteases or through dimerization, that ultimately result in distinct cellular responses. In some cases, allosteric modulation of PARs involves compartmentalization in caveolae, plasma membrane microdomains enriched in cholesterol. Here, we discuss some mechanisms that lead to allosteric modulation of PAR signaling.

Modifications of mechanoelectric feedback induced by 2,3-butanedione monoxime and Blebbistatin in Langendorff-perfused rabbit hearts.

AIM: Myocardial stretching is an arrhythmogenic factor. Optical techniques and mechanical uncouplers are used to study the mechanoelectric feedback. The aim of this study is to determine whether the mechanical uncouplers 2,3-butanedione monoxime and Blebbistatin hinder or modify the electrophysiological effects of acute mechanical stretch. METHODS: The ventricular fibrillation (VF) modifications induced by acute mechanical stretch were studied in 27 Langendorff-perfused rabbit hearts using epicardial multiple electrodes and mapping techniques under control conditions (n = 9) and during the perfusion of 2,3-butanedione monoxime (15 mM) (n = 9) or Blebbistatin (10 µm) (n = 9). RESULTS: In the control series, myocardial stretch increased the complexity of the activation maps and the dominant frequency (DF) of VF from 13.1 ± 2.0 Hz to 19.1 ± 3.1 Hz (P < 0.001, 46% increment). At baseline, the activation maps showed less complexity in both the 2,3-butanedione monoxime and Blebbistatin series, and the DF was lower in the 2,3-butanedione monoxime series (11.4 ± 1.2 Hz; P < 0.05). The accelerating effect of mechanical stretch was abolished under 2,3-butanedione monoxime (maximum DF = 11.7 ± 2.4 Hz, 5% increment, ns vs baseline, P < 0.0001 vs. control series) and reduced under Blebbistatin (maximum DF = 12.9 ± 0.7 Hz, 8% increment, P < 0.01 vs. baseline, P < 0.0001 vs. control series). The variations in complexity of the activation maps under stretch were not significant in the 2,3-butanedione monoxime series and were significantly attenuated under Blebbistatin. CONCLUSION: The accelerating effect and increased complexity of myocardial activation during VF induced by acute mechanical stretch are abolished under the action of 2,3-butanedione monoxime and reduced under the action of Blebbistatin.

[Assessment of an ELISA for the detection of antibodies against HIV-1 protein p24]. / Evaluación de un ELISA para la detección de anticuerpos contra la proteína p24 del VIH-1.

DAVIH AC p24 kit for detecting anti p24 antibodies of HIV-1, worked out by the National Laboratory of Reference of AIDS (Labor-1, Cuba) is assessed and results are compared to those of the Western Blot technique (DAVIH-Blot, Labor-1, Cuba). 191 samples from HIV positive patients at various stages of the disease were analyzed. 96% sensitivity; 100% specificity and 96.3% coincidence were found in both techniques. The anti p-24 ELISA-DAVIH system is a good alternative for the follow-up of HIV positive patients.

[The immunoassay of IgM antibodies in samples clinically suspected of measles]. / Inmunovaloración de anticuerpos IgM en muestras sospechosas de sarampión clínicamente.

60 matched sera clinically suspicious of measles that were received at the Diagnostic Laboratory of the "Pedro Kourí" Tropical Medicine Institute between January and May, 1996, coming from the seroepidemiological surveillance of the MPR vaccine were studied. The detection of measles and rubella hemagglutinant antibodies, as well as of IgM, was carried out with the Clark Laboratories INC. Measles IgM ELISA diagnostic kit. The positive cases were confirmed by the IgM-indirect immunofluorescence and neutralization. 3 positive cases to measles and rubella, which were negative to measles IgM, were obtained by hemagglutination inhibition. Antibodies against Epstein Barr, cytomegalovirus and herpes simplex virus were also determined by indirect immunofluorescence (IIF) due to the capacity of these viruses to induces polyclonal responses. 6 positive cases, which were negative by IIF, were detected by means of the above mentioned diagnostic kit.