Peroxynitrite mediates IL-8 gene expression and production in lipopolysaccharide-stimulated human whole blood

Recent evidence indicates that free oxygen radicals, in particular hydroxyl radicals, may act as intracellular second messengers for the induction of IL-8, a potent chemoattractant and activator of neutrophil granulocytes. Here we report that peroxynitrite (ONOO-), formed by a reaction of nitric oxide (NO) with superoxide, mediates IL-8 gene expression and IL-8 production in LPS-stimulated human whole blood. The NO synthase inhibitors aminoguanidine and NG-nitro-L-arginine methyl ester (L-NAME) blocked IL-8 release by approximately 90% in response to LPS (1 microg/ml), but did not affect the production of IL-1beta or TNF-alpha. Both aminoguanidine and L-NAME blocked the induction of IL-8 mRNA by LPS. Authentic ONOO- (2.5-80 microM) augmented IL-8 mRNA expression and stimulated IL-8 release in a concentration-dependent manner, whereas the NO-releasing compounds, S-nitroso-N-acetyl-DL-penicillamine and sodium nitroprusside failed to induce cytokine production. Combination of the NO-generating chemicals with a superoxide-generating system (xanthine/xanthine oxidase) markedly increased IL-8 release. Enhanced ONOO- formation was detected in granulocytes, monocytes, lymphocytes, and plasma after challenge with LPS. Furthermore, pyrrolidine dithiocarbamate, an inhibitor of activation of nuclear factor-gammaB, markedly attenuated the induction of IL-8 mRNA expression and IL-8 release by either LPS or ONOO-. Our study identifies ONOO- as a novel signaling mechanism for IL-8 gene expression and suggests that inhibition of ONOO- formation or scavenging ONOO- may represent a novel therapeutic approach to inhibit IL-8 production that could lead to reduction of neutrophil accumulation and activation.     

Diverticulitis of the cecum

Ten patients with diverticulitis of the cecum are reported upon herein. The disease is difficult to distinguish preoperatively from that of appendicitis and may be difficult to distinguish intraoperatively from carcinoma of the cecum. The diverticula are usually solitary and may be of the true or false variety. A review of the literature is presented, and the difficulties of diagnosis and treatment are discussed. We advocate local resection of the diverticulum, when possible, and a right hemicolectomy when the diagnosis is in doubt or when local resection or invagination would jeopardize the ileocecal valve or the blood supply to the intestine. With more awareness of diverticulitis of the cecum, intraoperative diagnosis may be made easier and the treatment simplified.     

The diagnosis and assessment of abdominal aortic aneurysms by ultrasonography

A study of 150 patients examined by ultrasonography is described. It was designed specifically to diagnose and investigate abdominal aortic aneurysms. Sixty-four aneurysms were found. Ultrasonography was useful in distinguishing aneurysms from other conditions and there was a high degree of correlation between size measured by scanning and operative size. In addition to the demonstration of rupture it was possible to perform serial measurements. The technique is simple and quick and causes minimal disturbance to the patient.     

Geographical boundaries of facial reconstruction

The principle of considering defined areas of the face as separate entities when planning reconstructive procedures is explained. The resurfacing of these individual areas is discussed, and the priorities in the order of reconstruction are defined.     

Mouse haemoglobin Beta chains. Sequence data on embryonic y chain and genetic linkage of the Y-chain locus to the adult beta-chain locus Hbb

Embryonic haemoglobin y-chain types were determined by starch-gel electrophoresis for inbred Mus musculus strains Sec/ReJ and Au/SsJ (with Hbbs and Hbbp adult beta-chain alleles respectively) and for random-bred HA/ICR (Swiss) mice, which had been selected to be homozygous for the adult Hbbd beta-chain allele. The strain with the Hbbs allele had y1 embryonic beta chain and the strain with the Hbbd allele had y2. The strain with the Hbbp allele also had y2 chain. A breeding study showed that the maximum recombination frequency between the Hbb locus and the y-chain locus is 5.4% at the 95% confidence level. Embryonic y2 chain was sequenced for 39 positions from the N-terminus with an Edman-Begg sequenator. Some tryptic-peptide composition data were obtained on both y1 and y2 chains. No amino acid substitutions between y1 and y2 chains were found in the 40 positions for which there are common data on the two chains. y2 and adult beta chains are different in 12 of the first 21 positions, but show considerable similarity thereafter. It is suggested that homologous but unequal crossing-over between y-chain and adult beta-chain loci could have given rise to the adult beta-chain allele Hbbd, which produces structurally different major and minor beta chains from two closely linked genes.