Shigella flexneri, a causative agent of bacterial dysentery, possesses two predicted iron-sulfur cluster biosynthesis systems called Suf and Isc. S. flexneri strains containing deletion mutations in the entire suf operon (UR011) or the iscSUA genes (UR022) were constructed. Both mutants were defective in surviving exposure to oxidative stress. The suf mutant showed growth that was comparable to that of the parental strain in both iron-replete and iron-limiting media; however, the isc mutant showed reduced growth, relative to the parental strain, in both media. Although the suf mutant formed wild-type plaques on Henle cell monolayers, the isc mutant was unable to form plaques on Henle cell monolayers because the strain was noninvasive. Expression from both the suf and isc promoters increased in iron-limiting media and in the presence of hydrogen peroxide. Iron repression of the suf promoter was mediated by Fur, and increased suf expression in iron-limiting media was enhanced by the presence of IscR. Iron repression of the isc promoter was mediated by IscR. Hydrogen peroxide-dependent induction of suf expression, but not isc expression, was mediated by OxyR. Furthermore, IscR was a positive regulator of suf expression in the presence of hydrogen peroxide and a negative regulator of isc expression in the absence of hydrogen peroxide. Expression from the S. flexneri suf and isc promoters increased when Shigella was within Henle cells, and our data suggest that the intracellular signal mediating this increased expression is reduced iron levels.As a facultative intracellular pathogen, Shigella flexneri spends a significant portion of its life cycle within the epithelial cells lining the human colon. Invasion of and intracellular survival/replication of the bacteria within these epithelial cells requires the ability to sense the environment and initiate an appropriate metabolic strategy during infection. Global analysis of Shigella transcription during epithelial cell infection indicated that a variety of metabolic genes, including the suf genes, are precisely regulated when Shigella is intracellular (16,27).The Shigella flexneri suf and isc loci encode predicted ironsulfur (Fe-S) cluster biosynthesis systems. Iron-sulfur clusters are essential for a wide variety of biological processes, including redox reactions, substrate binding and activation, iron storage, protein structure, and regulation of gene expression (11). The S. flexneri isc locus contains iscR, iscS, iscU, iscA, hscB, hscA, and fdx and is highly conserved with the Escherichia coli isc locus. E. coli IscS catalyzes the desulfurization of L-cysteine for the recruitment of S for Fe-S cluster formation (4). IscU and IscA are predicted to form scaffolds for Fe-S cluster assembly based on similarities with Azobacter vinelandii NifU and IscA Nif (1, 11, 13). The chaperones HscB and HscA aid in Isc-mediated Fe-S protein maturation, although the specifics are not entirely clear (for a review, see reference 11). Deletion of the isc locus in E. coli reduced the gro...

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Dr Hillhouse had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Baker and Hillhouse. Acquisition of data: Hillhouse.

This report examines outcomes of revascularization for acute arterial mesenteric ischemia (AAMI) using the American College of Surgeons National Surgical Quality Improvement Program database. Patients with International Classification of Diseases, 9th Revision and Current Procedural Terminology codes indicating AAMI with concomitant mesenteric revascularization were identified. Demographic, risk factor, procedural, morbidity, and mortality data were examined. Associations with morbidity and mortality were analyzed by logistic regression. One hundred forty-two cases of AAMI were identified. Seventy-one cases were thrombotic and 71 were embolic according to revascularization codes. Mean age was 66 years, 84 per cent of patients were white, and 54 per cent were female. Unadjusted major morbidity and mortality rates were 69 and 30 per cent, respectively. Patients with thrombotic AAMI were more likely to have a lower body mass index, greater than 10 per cent weight loss in the past 6 months, and a history of smoking. Patients with embolic AAMI were more likely to present emergently with sepsis. Unadjusted morbidity and mortality rates were 78 and 38 per cent for embolic and 61 and 23 per cent for thrombotic AAMI, respectively. Multi-variable predictors of morbidity included bowel resection at the time of revascularization, transfer admission, and involvement of a surgical resident. Multivariable predictors of mortality included impaired functional status, increased age, and postoperative sepsis. Cause of AAMI was not a significant predictor of morbidity or mortality. In a large sample of AAMI cases, AAMI remained a highly lethal and morbid condition. Predictors of morbidity and mortality included indicators of advanced presentation, treatment delay, and patient-related factors specific to AAMI, including debility and advanced age. Efforts directed at prevention and increasing the speed of diagnosis and definitive treatment appear to be necessary to improve outcomes.

Background: Pachydermodactyly is a rare, benign, acquired form of digital fibromatosis. The etiology of pachydermodactyly is unknown but is believed to be due to repeated mechanical injury of the skin. We report 2 cases identified in poultry processing workers and review other conditions associated with these cutaneous findings. Observations: The 2 workers in this report were employed as a chicken catcher and a chicken hanger. On examination, both workers had marked lateral thickening of the digits, with associated pain and pruritus. The workers' skin condition developed despite the use of protective gloves, and their symptoms improved when removed from work. However, the swelling due to fibromatosis persisted. Conclusions: Similar cutaneous findings have been reported in other occupations exposing individuals to repetitive skin trauma, and many patients demonstrating a compulsive habit of hand manipulation. This supports the conclusion that pachydermodactyly in these patients reflects repeated skin trauma. Repetitive mechanical injury in the poultry processing environment can result in considerable compensatory tissue changes. Preventive measures are needed to protect workers.