Formation of mitochondrial phospholipid adducts by nephrotoxic cysteine conjugate metabolites.

Nephrotoxic cysteine conjugates derived from a variety of halogenated alkenes are enzymatically activated via the beta-lyase pathway to yield reactive sulfur-containing metabolites which bind covalently to cellular macromolecules. Mitochondria contain beta-lyase enzymes and are primary targets for binding and toxicity. Previously, mitochondrial protein and/or DNA have been considered as molecular targets for cysteine conjugate metabolite binding. We now report that metabolites of nephrotoxic cysteine conjugates form covalent adducts with rat kidney mitochondrial phospholipids. Rat kidney mitochondria were incubated with the 35S-labeled conjugates S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC), S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC), S-(1,2-dichlorovinyl)-L-cysteine, and S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine. Quantitation of metabolite binding to whole mitochondria and to mitochondrial protein and lipid fractions revealed that as much as 42% of the 35S-label associated with the mitochondria was found in the lipid fraction. Total lipids were also extracted from 35S-treated mitochondria and separated by thin-layer chromatography. 35S-Containing metabolites were found in the lipid fractions from mitochondria treated with each of the conjugates. Lipids from both [35S]CTFC- and [35S]-TFEC-treated mitochondria contained major 35S-labeled lipid adducts which had similar mobility by thin-layer chromatography. Fatty acid analysis, 19F and 31P NMR spectroscopy, and mass spectrometric analyses confirmed that the major TFEC and CTFC adducts are thioamides of phosphatidylethanolamine.     

Preventing the airborne spread of Staphylococcus aureus by persons with the common cold: effect of surgical scrubs, gowns, and masks.

OBJECTIVE: Transmission of Staphylococcus aureus via air may play an important role in healthcare settings. This study investigates the impact of barrier precautions on the spread of airborne S. aureus by volunteers with experimentally induced rhinovirus infection (ie, the common cold). DESIGN: Prospective nonrandomized study. SETTING: Wake Forest University School of Medicine (Winston-Salem, NC).Participants. A convenience sample of 10 individuals with nasal S. aureus carriage selected from 593 students screened for carriage. INTERVENTION: Airborne S. aureus dispersal was studied in the 10 participants under the following clothing conditions: street clothes, surgical scrubs, surgical scrubs and a gown, and the latter plus a face mask. After a 4-day baseline period, volunteers were exposed to a rhinovirus, and their clinical course was followed for 12 days. Daily swabs of nasal specimens, pharynx specimens, and skin specimens were obtained for quantitative culture, and cold symptoms were documented. Data were analyzed by random-effects negative binomial models. RESULTS: All participants developed a common cold. Incidence rate ratios (IRRs) indicated that, compared with airborne levels of S. aureus during sessions in which street clothes were worn, airborne levels decreased by 75% when surgical scrubs were worn (P<.001), by 80% when scrubs and a surgical gown were worn (P<.001), and by 82% when scrubs, a gown, and a face mask were worn (P<.001). The addition of a mask to the surgical scrubs and gown did not reduce the airborne dispersal significantly (IRR, 0.92; P>.05). Male volunteers shed twice as much S. aureus as females (incidence rate ratio, 2.04; P=.013). The cold did not alter the efficacy of the barrier precautions. CONCLUSIONS: Scrubs reduced the spread of airborne S. aureus, independent of the presence of a rhinovirus-induced cold. Airborne dispersal of S. aureus during sessions in which participants wore surgical scrubs was not significantly different from that during sessions in which gowns and gowns plus masks were also worn.     

Linkage studies and mutation analysis of the PDEB gene in 23 families with Leber congenital amaurosis.

The phenotype in the rd mouse is similar to the clinical presentation of Leber congenital amaurosis (LCA) in humans. Recently a nonsense mutation in the beta subunit of the cGMP phosphodiesterase (Pdeb) gene has been defined as the cause for the rd phenotype in the mouse and has raised the question as to whether mutations in the human PDEB gene might cause LCA. We have previously cloned and characterized the human homologue of the mouse Pdeb gene and have mapped it to chromosome 4p16.3. In this study, a total of 23 LCA families of various ethnic backgrounds have been investigated. Linkage analysis using highly polymorphic (CA)n microsatellites has excluded the PDEB gene as a cause for LCA in 6 families. In the remaining 17 families, we have searched for mutations in the 22 exons of the PDEB gene using single-strand gel electrophoresis (SSGE). Multiple exonic polymorphisms have been determined. However, no DNA changes in the PDEB gene have been identified in our study population which could be causative for the LCA phenotype.     

Colorectal Cancer Screening Pilot Program for Underserved Women in Cumberland County,Maine

Over 800 Maine residents will be diagnosed with colorectal cancer (CRC) this year, and nearly 300 will die from the disease. While CRC screening can reduce these rates, it is only among insured populations that screening rates exceed 50%. This project aimed to reduce barriers to, and increase rates of CRC screening among underinsured and uninsured women, ages 50 years and over, residing in Cumberland County, Maine. The existing network of the Maine Breast and Cervical Health Program (MBCHP) was used to reach the target population. A packet containing (1) an offer for no-cost fecal occult blood test (FOBT) screening and CRC-related educational materials, and (2) a stamped, addressed postcard specifying the woman’s interest in these resources, was mailed to 300 MBCHP enrollees residing in Cumberland County. Women requesting screening were contacted by phone to further determine eligibility. Ninety-three women (31%) requested FOBT kits and 29 of these women requested educational materials. Ten women were ineligible for screening because of previous colonoscopy. Fifty-two completed FOBT kits (63%) were returned; all were negative. An additional 42 (14%) women requested educational materials only. To reduce the burden of CRC in Maine and nationally, disparate populations must be reached with efficient and effective screening services. Established networks are proven means for reaching uninsured and underinsured individuals with education, screening services, and necessary follow-up care. This project serves as a model for the future development of similar programs statewide and nationally.