Citations

Molecular dynamics simulations have been used to assess the conformational behaviour of seven disaccharides in aqueous solution. Solvation decreased the overall conformational fluctuations of the sugars, compared to in vacuo simulations using a high dielectric constant. The most significant finding was a linear correlation between the experimental chromatographic retention parameter K´ and a molecular modelling parameter based on the next-nearest oxygen–oxygen distances in the disaccharides. The results support previous proposals for a stereospecific hydration model for carbohydrates and demonstrate the utility of a combined experimental/molecular modelling approach to its study.

ABSTRACT Mycobacterium peregrinum consists of two taxa: types I and II. We evaluated 43 clinical type II strains from throughout the United States. They were responsible for soft-tissue and bone infections, catheter-related infections, and possible pneumonitis. By carbohydrate utilization, they were indistinguishable from type I strains, being d -mannitol and trehalose positive. However, they had a distinct susceptibility pattern that included intermediate ciprofloxacin MICs but low clarithromycin and doxycycline MICs of ≤1 μg/ml. These features were also shared by reference isolates of Mycobacterium senegalense from African bovine cases of “farcy.” By 16S rRNA gene sequencing, the type II isolates shared 100% sequence identity with M. senegalense . Partial sequencing of the type II hsp65 gene (441 bp) revealed four sequevars showing ≥98.4% identity with each other and ≥98.6% identity with the sequence of five bovine strains of M. senegalense . There was ≤97.1% identity with M. peregrinum type I isolates and other Mycobacterium fortuitum group species. Sequencing of additional gene targets including the 16S-23S rDNA internal transcribed spacer region and the rpoB gene (partial sequence) revealed a similar phylogenetic grouping. DNA-DNA hybridization showed 76 to 99% relatedness between the bovine and human strains. These studies demonstrate that type II isolates are not isolates of M. peregrinum but represent human strains of M. senegalense . This study is the first to demonstrate this species as a human pathogen. Representative human M. senegalense strains include ATCC 35755 and newly submitted strains ATCC BAA-849, ATCC BAA-850, and ATCC BAA-851.

Background— Unlike the Western world, valvular disease ranks among the major cardiovascular afflictions in Africa. Acute rheumatic fever and chronic rheumatic valvular disease in their most virulent form are still commonly encountered and impose a huge burden on limited healthcare resources. Methods and Results— We performed a systematic review of the literature with PubMed using rheumatic fever , rheumatic heart disease , valvular disease , warfarin anticoagulation , and pregnancy as search items. Literature emanating from Africa was emphasized. Epidemiology, current concepts on pathogenesis, and aspects of the medical and surgical management of this disease as seen from an African perspective are presented. The association of pregnancy with mitral stenosis is common and may be fatal if not managed appropriately. A practical approach to these patients is presented to optimize maternal and fetal outcome. Pregnant patients with mechanical valves require careful attention to ensure maternal survival and prevent fetal warfarin embryopathy. Prolonged subcutaneous heparin and frequent monitoring of the partial thromboplastin time are impractical in this setting, and the merits of different anticoagulation regimens are discussed. Congenital submitral aneurysms are a unique cause of mitral regurgitation, with the vast majority of cases originating from sub-Saharan Africa. Although the precise etiology is as yet unclear, the clinical and echocardiographic features are sufficiently characteristic to allow a preoperative diagnosis to be made. Transesophageal echocardiography allows much better definition of the size and anatomic relationships of the aneurysm. Surgical resection can be difficult but is usually curative. Mitral valve prolapse and endocarditis constitute the remaining frequent causes of valvular disease and are discussed briefly. Conclusions— The spectrum and presentation of valvular disease in Africa are uniquely different from elsewhere. Together with socioeconomic issues and the HIV pandemic, this fact makes it imperative that further epidemiological and clinical studies be undertaken and guidelines developed that are appropriate to the practice of medicine on the African continent.

Headaches are quite common in children and adolescents, and they appear to persist into adulthood in a sizable number of individuals. Assessment approaches (interview, pain diaries, and general and specific questionnaires) and behavioral treatment interventions (contingency management, relaxation, biofeedback, and cognitive behavior therapy) are reviewed, as is the evidence base for their use. The article concludes with practical suggestions for headache management.

Abstract Polychlorinated biphenyls (PCB) have been suspected as possible contributors to increasing non-Hodgkin's lymphoma incidence during the latter half of the 20th century based on their toxicologic properties and provocative epidemiologic reports. We investigated PCBs and other organochlorines and risk of non-Hodgkin's lymphoma in a population-based case-control study in the United States. Congeners of PCBs (including coplanar congeners), dioxins, furans and pesticides or pesticide metabolites were measured in plasma of 100 untreated cases and 100 control subjects. We used a multiple imputation procedure to fill in missing values of levels determined to be below the detection limits. Risks of non-Hodgkin's lymphoma associated with each analyte were estimated using conditional logistic regression for the continuous measure, exposure quartiles, trend across quartile categories, and exposures above the 95th percentile. Certain PCB congeners were associated with increased risk of non-Hodgkin's lymphoma, including coplanar PCBs 156, 180, and 194, with odds ratios for the highest versus lowest quartile ranging from 2.7 to 3.5, and significant trends. Each of the furan congeners was associated with risk of non-Hodgkin's lymphoma, as were total furans, with 3.5-fold increased risk for the highest versus lowest quartile and a significant trend across quartiles (P = 0.006). The toxic equivalency quotient (TEQ), a summed metric that weights congeners by their dioxin-like potency, was associated with non-Hodgkin's lymphoma, with 35% increased risk per 10 TEQ pg/g lipid (95% confidence interval, 1.02-1.79). Our results add to existing literature, which suggests that exposure to organochlorines contributes to non-Hodgkin's lymphoma risk; these risks were most apparent for certain PCBs and furans.

Abstract Aromatase [cytochrome P450 19 (CYP19)] is a critical enzyme for estrogen biosynthesis, and aromatase inhibitors are of increasing importance in the treatment of breast cancer. We set out to identify and characterize genetic polymorphisms in the aromatase gene, CYP19, as a step toward pharmacogenomic studies of aromatase inhibitors. Specifically, we “resequenced” all coding exons, all upstream untranslated exons plus their presumed core promoter regions, all exon-intron splice junctions, and a portion of the 3′-untranslated region of CYP19 using 240 DNA samples from four ethnic groups. Eighty-eight polymorphisms were identified, resulting in 44 haplotypes. Functional genomic studies were done with the four nonsynonymous coding single nucleotide polymorphisms (cSNP) that we observed, two of which were novel. Those cSNPs altered the following amino acids: Trp39Arg, Thr201Met, Arg264Cys, and Met364Thr. The Cys264, Thr364, and double variant Arg39Cys264 allozymes showed significant decreases in levels of activity and immunoreactive protein when compared with the wild-type (WT) enzyme after transient expression in COS-1 cells. A slight decrease in protein level was also observed for the Arg39 allozyme, whereas Met201 displayed no significant changes in either activity or protein level when compared with the WT enzyme. There was also a 4-fold increase in apparent Km value for Thr364 with androstenedione as substrate. Of the recombinant allozymes, only the double mutant (Arg39Cys264) displayed a significant change from the WT enzyme in inhibitor constant for the aromatase inhibitors exemestane and letrozole. These observations indicate that genetic variation in CYP19 might contribute to variation in the pathophysiology of estrogen-dependent disease.