Mutations Affecting the Rossman Fold of Isoleucyl-tRNA Synthetase Are Correlated with Low-Level Mupirocin Resistance in Staphylococcus aureus

The isoleucyl-tRNA synthetase (ileS) gene was sequenced in toto from 9 and in part from 31 Staphylococcus aureus strains with various degrees of susceptibility to mupirocin. All strains for which the mupirocin MIC was greater than 8 microg/ml contained point mutations affecting the Rossman fold via Val-to-Phe changes at either residue 588 (V588F) or residue 631 (V631F). The importance of the V588F mutation was confirmed by an allele-specific PCR survey of 32 additional strains. Additional mutations of uncertain significance were found in residues clustered on the surface of the IleS protein.     

Role of nitric oxide in relaxation of the longitudinal layer of rectal smooth muscle

PURPOSE: This study was designed to investigate the role of nitric oxide in neurogenic relaxation of the longitudinal layer of human rectal smooth muscle. METHODS: Tissue was obtained from the mid rectum of patients undergoing anterior resection for carcinoma. Adjacent strips of longitudinal muscle were dissected and mounted in organ baths for isometric tension recording. In preliminary experiments to determine the response of strips to cholinergic, adrenergic, and potential excitatory agonists, strips were superfused with standard Krebs solution (37±0.5°C; pH, 7.4±0.05). Investigation of inhibitory, nonadrenergic noncholinergic responses required the addition of 3×10⁻⁶ M histamine to induce reproducible and stable tension for five-minute “test” periods, during which electrical field stimulation (EFS) and additional drugs were applied. In these experiments, strips were superfused with Krebs solution that contained atropine sulfate (3×10⁻⁶ M) and guanethidine (3×10⁻⁶ M). RESULTS: The response to cholinergic and adrenergic agonists was typical of nonsphincter specialized gastrointestinal smooth muscle. EFS elicited frequency-dependent, neurogenic (tetrodotoxin-sensitive) relaxations of precontracted strips, which were reduced in dose-dependent fashion by addition ofNω-nitro-l-arginine and restored by addition of 3×10 ⁻⁴ M l-arginine but not by d-arginine. Addition of exogenous nitric oxide (sodium nitroprusside) mimicked the relaxant response induced by EFS. CONCLUSION: Smooth muscle from the longitudinal layer of human rectum receives an intrinsic inhibitory innervation mediated by nitric oxide. Supported and financed by the Medical Research Council, United Kingdom. John Stebbing is in receipt of a Medical Research Council Clinical Training Fellowship. Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.     

Effective epilation of white and blond hair using combined radiofrequency and optical energy.

OBJECTIVE: The present study examined the long-term photoepilatory effect on blond and white hair of a combined intense pulsed light (680-980 nm) device with a bipolar radiofrequency component producing electrical current at a depth of 4 mm. MATERIALS AND METHODS: Thirty-six adult women with white and blond hair (skin phenotypes I-V) were included in the study. The chin and upper lip were treated with four treatment sessions over 9-12 months with long-term follow-up performed at month 18 (6 months after the last treatment). The level of RF energy was 20 J/cm3, while optical fluences varied from 24 to 30 J/cm2. Hair counts and photographic evaluation of some sites were obtained at baseline, months 1, 3 and 5 and the final treatment session. RESULTS: An average hair removal of 48% was observed at month 18 (6 months following the final treatment session). A slightly higher photoepilatory efficiency was noted for blond hair (52%) versus white hair (44%) treatment sites. CONCLUSION: Combined radiofrequency and optical energy technology may produce effective photoepilation of blond and white hair phenotypes.     

Multivesicular liposomes containing 1-beta-D-arabinofuranosylcytosine for slow-release intrathecal therapy

Optimal anticancer treatment with cell cycle-specific antimetabolites requires maintenance of a cytotoxic drug level for a prolonged period of time. We explored the use of multivesicular liposomes as a slow-release depot of 1-beta-D-arabinofuranosylcytosine for intrathecal administration. The intrathecal half-life of the liposome-encapsulated drug was 148 h, in contrast to the half-life of 2.7 h for the unencapsulated free drug, in a Sprague-Dawley rat model. The prolonged maintenance of a therapeutic drug level may increase efficacy, and the elimination of the very high peak level may decrease toxicity.     

Influence of TNFalpha and LTalpha single nucleotide polymorphisms on susceptibility to and prognosis in cutaneous malignant melanoma in the British population.

Cutaneous malignant melanoma (CMM) is a potentially fatal malignancy in which exposure to UV light is the most important risk factor. Several lines of evidence suggest that increased expression of tumour necrosis factor (TNF) alpha, upregulated by UV exposure, may contribute to tumour escape from the immune response. In this study, we addressed whether single nucleotide polymorphisms (SNPs) in the TNFalpha promoter and lymphotoxin (LT) alpha gene are associated with susceptibility to or known prognostic indicators (e.g. initial tumour growth phase, Breslow thickness, mitotic count in vertical growth phase tumours, and tumour regression) in CMM. One hundred and forty-six British Caucasian CMM patients and 220 controls were typed for TNFalpha-376, -308 and -238 and LTalpha+252 SNPs by ARMS-PCR. Only the TNFalpha -238 GG (P = 0.05) and GA (P = 0.03) genotypes showed slight, but significant, associations with CMM, while LTalpha+252 AA was associated with a higher mitotic count in vertical growth phase tumours (P = 0.02). Both TNFalpha-238 and LTalpha+252 SNPs showed linkage disequilibrium with HLA-DQB1*0303 and *0301 alleles, variably implicated in CMM susceptibility/prognosis. In addition, TNFalpha-238, -308, LTalpha+252 haplotypes were assigned and compared. The GGA haplotype showed a modest association with CMM (P = 0.04) and with stage of disease (P = 0.03) and initial growth phase in CMM (P = 0.02), but these associations were only significant when P-values were uncorrected. Unlike basal cell carcinoma, these preliminary findings suggest that genetic variation associated with differential TNFalpha and LTalpha production is unlikely to play a major, independent role in susceptibility to, and perhaps prognosis in, CMM.