Eradication of a given pathogen is dependent on the selective differentiation of T helper (Th) cells into Th1 or Th2 types. We show here that T cells from mice lacking the transcription factor IRF-1 fail to mount Th1 responses and instead exclusively undergo Th2 differentiation in vitro. Compromised Th1 differentiation is found to be associated with defects in multiple cell types, namely impaired production of interleukin-12 by macrophages, hyporesponsiveness of CD4+ T cells to interleukin-12, and defective development of natural killer cells. These results indicate the involvement of IRF-1 in multiple stages of the Th1 limb of the immune response.

The role of phospholipase A2 (PLA2) in lung injury in humans is unclear. Previous studies have failed to identify an increase in PLA2 activity in bronchoalveolar lavage fluids (BALF) of patients with the adult respiratory distress syndrome (ARDS). In this study, increased phospholipase A2 (PLA2) activity was detected in BALF from patients with ARDS. PLA2 levels in BALF correlated positively with lung injury score in patients with lung disease. BALF PLA2 activity in patients with ARDS was resolved into heparin binding and nonbinding activities. Both PLA2 activities were increased in BALF of ARDS patients. The PLA2 activity that bound to heparin was identified as a group II PLA2 by its chromatographic characteristics, its inhibition by dithiothreitol, its substrate specificity, and its approximate molecular mass of 14 kDa. The second PLA2 activity was further purified and found to require Ca2+ at a concentration > 2 x 10(-4) M for activity. This form of PLA2 exhibited a neutral and broad pH optimum (pH 6.0-8.0) and hydrolyzed both phosphatidylethanolamine and phosphatidylcholine effectively. Its apparent molecular mass was estimated to be 80-90 kDa. Neither anti-pancreatic PLA2 antiserum nor anti-pig spleen cytosolic 100-kDa PLA2 antiserum immunoprecipitated the enzymatic activity. Thus at least two forms of PLA2 are increased in activity in BALF of patients with ARDS, a group II PLA2 and a biochemically and immunochemically form distinct from group I, group II, and cytosolic PLA2. Increased lung PLA2 activity may be important for the pathophysiology of ARDS.

Background The long-term clinical issue in Kawasaki disease (KD) concerns the coronary artery lesion. Two-dimen-

AimEarly prediction of prognosis after out‐of‐hospital cardiac arrest (OHCA) remains difficult. High blood lactate or low pH levels may be associated with poor prognosis in OHCA patients, but these associations remain controversial. We compared blood lactate and pH levels in OHCA patients transferred to our hospital to measure their prognostic performance.MethodsWe investigated the associations between blood lactate and pH levels on admission and neurological outcomes in 372 OHCA patients who had a return of spontaneous circulation.ResultsOf the 372 OHCA patients, 31 had a favorable neurological outcome. Blood lactate levels were lower in patients with a favorable outcome than in those with an unfavorable outcome, but this difference did not reach statistical significance (82 ± 49 vs. 96 ± 41 mg/dL). However, pH levels were significantly higher in patients with a favorable outcome than in those with an unfavorable outcome (7.26 ± 0.16 vs. 6.93 ± 0.19, P < 0.001). The relative cumulative frequency distribution curve analysis showed the optimal cut‐off points of lactate and pH to be approximately 80 mg/dL and 7.05, respectively. Sensitivity and specificity to predict a favorable outcome were 61% and 64% for lactate <80 mg/dL and 84% and 80% for pH >7.05, respectively. Areas under receiver–operating characteristic curves were significantly larger for pH than for lactate levels (P < 0.001). In multivariate analysis, pH >7.05 was an independent predictor for a favorable outcome.ConclusionAfter OHCA, patients with a favorable outcome had lower lactate and higher pH levels than those with an unfavorable outcome, but pH level was a much better predictor for neurological outcome than lactate levels.