Citations

Background— The incidence and significance of gasping after cardiac arrest in humans are controversial. Methods and Results— Two approaches were used. The first was a retrospective analysis of consecutive confirmed out-of-hospital cardiac arrests from the Phoenix Fire Department Regional Dispatch Center text files to determine the presence of gasping soon after collapse. The second was a retrospective analysis of 1218 patients with out-of-hospital cardiac arrests in Arizona documented by emergency medical system (EMS) first-care reports to determine the incidence of gasping after arrest in relation to the various EMS arrival times. The primary outcome measure was survival to hospital discharge. An analysis of the Phoenix Fire Department Regional Dispatch Center records of witnessed and unwitnessed out-of-hospital cardiac arrests with attempted resuscitation found that 44 of 113 (39%) of all arrested patients had gasping. An analysis of 1218 EMS-attended, witnessed, out-of-hospital cardiac arrests demonstrated that the presence or absence of gasping correlated with EMS arrival time. Gasping was present in 39 of 119 patients (33%) who arrested after EMS arrival, in 73 of 363 (20%) when EMS arrival was <7 minutes, in 50 of 360 (14%) when EMS arrival time was 7 to 9 minutes, and in 25 of 338 (7%) when EMS arrival time was >9 minutes. Survival to hospital discharge occurred in 54 of 191 patients (28%) who gasped and in 80 of 1027 (8%) who did not (adjusted odds ratio, 3.4; 95% confidence interval, 2.2 to 5.2). Among the 481 patients who received bystander cardiopulmonary resuscitation, survival to hospital discharge occurred among 30 of 77 patients who gasped (39%) versus only 38 of 404 among those who did not gasp (9%) (adjusted odds ratio, 5.1; 95% confidence interval, 2.7 to 9.4). Conclusions— Gasping or abnormal breathing is common after cardiac arrest but decreases rapidly with time. Gasping is associated with increased survival. These results suggest that the recognition and importance of gasping should be taught to bystanders and emergency medical dispatchers so as not to dissuade them from initiating prompt resuscitation efforts when appropriate.

Activation of CD4+ T cells is governed by interplay between stimulatory and inhibitory receptors; predominance of stimulatory signals favors autoimmune reactions. In patients with rheumatoid arthritis, expression of the critical costimulatory molecule, CD28, is frequently lost. Instead, CD4+CD28null T cells express killer immunoglobulin-like receptors (KIRs) with a preferential expression of the stimulatory receptor, CD158j. The frequency of CD4+CD28null T cells in rheumatoid arthritis (RA) correlates with the risk for more severe disease. Moreover, the KIR2DS2 gene, which encodes for CD158j, is a genetic risk factor for rheumatoid vasculitis. CD158j signals through the adaptor molecule, KARAP/DAP12, to positively regulate cytotoxic activity in NK cells. However, the majority of CD4+CD28null T cell clones lacked the expression of KARAP/DAP12. Despite the absence of KARAP/DAP12, CD158j was functional and augmented interferon-γ production after T cell receptor stimulation. Cross-linking of CD158j resulted in selective phosphorylation of c-Jun NH2-terminal protein kinase (JNK) and its upstream kinase, MKK4 that led to the expression of ATF-2 and c-Jun, all in the absence of extracellular signal–regulated kinase (ERK)1/2 phosphorylation. Mutation of the lysine residue within the transmembrane domain of CD158j abolished JNK activation, suggesting that an alternate adaptor molecule was being used. CD4+CD28null T cells expressed DAP10 and inhibition of phosphatidylinositol 3-kinase, which acts downstream of DAP10, inhibited JNK activation; however, no interaction of DAP10 with CD158j could be detected. Our data suggest that CD158j in T cells functions as a costimulatory molecule through the JNK pathway independent of KARAP/DAP12 and DAP10. Costimulation by CD158j may contribute to the autoreactivity of CD4+CD28null T cells in RA.

Single-molecule atomic force microscopy (AFM) was used to investigate the mechanical properties of titin, the giant sarcomeric protein of striated muscle. Individual titin molecules were repeatedly stretched, and the applied force was recorded as a function of the elongation. At large extensions, the restoring force exhibited a sawtoothlike pattern, with a periodicity that varied between 25 and 28 nanometers. Measurements of recombinant titin immunoglobulin segments of two different lengths exhibited the same pattern and allowed attribution of the discontinuities to the unfolding of individual immunoglobulin domains. The forces required to unfold individual domains ranged from 150 to 300 piconewtons and depended on the pulling speed. Upon relaxation, refolding of immunoglobulin domains was observed.