Anthony W. Ford‐Hutchinson

The rate-limiting step in the formation of prostanoids is the conversion of arachidonic acid to prostaglandin H2 by cyclooxygenase, also known as prostaglandin G/H synthase/cyclooxygenase. Two forms of cyclooxygenase have been characterized: a ubiquitously expressed form (COX-1) and a recently described second form (COX-2) inducible by various factors including mitogens, hormones, serum and cytokines. Here we quantitate by the reverse transcriptase-polymerase chain reaction (RT-PCR) the expression of COX-1 and COX-2 mRNA in human tissues including lung, uterus, testis, brain, pancreas, kidney, liver, thymus, prostate, mammary gland, stomach and small intestine. All tissues examined contained both COX-1 and COX-2 mRNA and could be grouped according to the level of COX mRNA expression. The highest levels of COX mRNAs were detected in the prostate where approximately equal levels of COX-1 and COX-2 transcripts were present. In the lung high levels of COX-2 were observed whereas COX-1 mRNA levels were about 2-fold lower. An intermediate level of expression of both COX-1 and COX-2 mRNA was observed in the mammary gland, stomach, small intestine, and uterus. The lowest levels of COX-1 and COX-2 mRNA were observed in the testis, pancreas, kidney, liver, thymus, and brain.

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More

Urinary leukotriene E4 (LTE4) concentrations have been measured in six asthmatic patients with aspirin sensitivity and in five asthmatic subjects tolerant of aspirin, before and after provocation with aspirin or placebo. Aspirin-sensitive subjects showed an average 21% fall in FEV1 after aspirin challenge whereas control individuals had a 2% fall in FEV1 after ingestion of 100 mg aspirin. The resting urinary LTE4 concentrations in asthmatic subjects sensitive to aspirin were 243 pg/mg creatinine (range 50 to 1,041), and these were on average sixfold greater than those in control asthmatic subjects. Further, there was a mean fourfold increase in urinary LTE4 levels at 3 to 6 h after aspirin, but not placebo, challenge in aspirin-sensitive asthmatic subjects that was not seen in the control asthmatic individuals. Leukotriene release may play a central role in the mechanisms of asthmatic attacks produced by aspirin ingestion.