Comparative genomic indexing reveals the phylogenomics of Escherichia coli pathogens

The Escherichia coli O26 serogroup includes important food-borne pathogens associated with human and animal diarrheal disease. Current typing methods have revealed great genetic heterogeneity within the O26 group; the data are often inconsistent and focus only on verotoxin (VT)-positive O26 isolates. To improve current understanding of diversity within this serogroup, the genomic relatedness of VT-positive and -negative O26 strains was assessed by comparative genomic indexing. Our results clearly demonstrate that irrespective of virulence characteristics and pathotype designation, the O26 strains show greater genomic similarity to each other than to any other strain included in this study. Our data suggest that enteropathogenic and VT-expressing E. coli O26 strains represent the same clonal lineage and that VT-expressing E. coli O26 strains have gained additional virulence characteristics. Using this approach, we established the core genes which are central to the E. coli species and identified regions of variation from the E. coli K-12 chromosomal backbone.     

Extravasation and transcytosis of liposomes in Kaposi's sarcoma-like dermal lesions of transgenic mice bearing the HIV tat gene.

Transgenic mice bearing the HIV tat gene develop dermal lesions resembling a common malignant tumor in AIDS, Kaposi's sarcoma (KS). To evaluate the permeability characteristics of these lesions and the therapeutic potential of drug-carrying liposomes, we have studied the localization of sterically stabilized liposomes, which show long circulation time in blood and increased accumulation in tumors. Liposomes encapsulating colloidal gold were injected intravenously into transgenic mice bearing KS lesions, and tissues were processed 24 hours later for both electron microscopy and for light microscopy with silver enhancement. Liposomes and silver marker were detected predominantly in the dermis surrounding the early and mature KS lesions, which were characterized by a proliferation of fibroblast-like spindle cells and abnormal blood vessels close to the epidermis. The silver-enhanced gold marker often surrounded vascular channels and scattered erythrocytes. As determined by electron microscopy, some spindle cells and macrophages had ingested intact liposomes. Transendothelial transport of liposomes was observed both through open channels between endothelial cells and also through endothelial cells lining intact vessels. Both extravasation and transcytosis of liposomes through irregular endothelium were much higher in KS lesions than in the adjacent normal skin. The high accumulation of sterically stabilized liposomes in KS lesions and their intracellular uptake by some spindle cells enhances their potential as carriers of chemotherapeutic agents against this neoplasm.     

Serial Testing of Postural Control After Acute Lateral Ankle Sprain

OBJECTIVE: To identify subjects' changes in postural control during single-leg stance in the 4 weeks after acute lateral ankle sprain. DESIGN AND SETTING: We used a 2 x 2 x 3 (side-by-plane-by-session) within-subjects design with repeated measures on all 3 factors. All tests were performed in a university laboratory. SUBJECTS: Seventeen young adults (9 men, 8 women; age, 21.8 +/- 5.9 years; mass, 74.9 +/- 10.5 kg; height, 176.9 +/- 7.1 cm) who had sustained unilateral acute mild or moderate lateral ankle sprains. MEASUREMENTS: Measures of center-of-pressure excursion length, root mean square velocity of center-of-pressure excursions (VEL), and range of center-of-pressure excursions (RANGE) were calculated separately in the frontal and sagittal planes during 5-second trials of static single-leg stance. RESULTS: We noted significant side-by-plane-by-session interactions for magnitude of center-of-pressure excursions in a given trial (PSL) (P =.004), VEL (P =.011), and RANGE (P =.009). Both PSL and VEL in the frontal plane were greater in the injured limbs compared with the uninjured limbs on day 1 and during week 2 but not during week 4, whereas sagittal-plane differences existed during all 3 testing sessions. Injured-limb, frontal-plane RANGE scores were greater than uninjured values at day 1 but not during weeks 2 or 4. No significant differences in sagittal-plane RANGE scores were seen. CONCLUSIONS: Postural control was significantly impaired in the injured limbs at day 1 and during week 2 after lateral ankle sprain but not during week 4. Consistent improvement in postural control measures on both injured and uninjured limbs was seen throughout the 4 weeks after ankle sprain.     

Linkage refinement localises Sorsby fundus dystrophy between markers D22S275 and D22S278.

Sorsby fundus dystrophy is an autosomal dominant disorder which both clinically and histopathologically bears striking similarities to age related macular degeneration, one of the leading causes of blindness in the developed world. Recent studies have suggested a genetic localisation of the disease to chromosome 22q in a large genetic interval of approximately 25 cM. Independent genetic linkage analysis in a six generation British pedigree confirms linkage to the chromosome 22q region. A maximum two point lod score of 7.09 with no recombination was obtained with marker D22S280. Haplotype data positioned the disease between loci D22S275 and D22S278, thus significantly reducing the region on chromosome 22q where the gene is located.     

Antigen-specific T cell suppression by human CD4+CD25+ regulatory T cells

Anergic/suppressive CD4+CD25+ T cells have been proposed to play an important role in the maintenance of peripheral tolerance. Here we demonstrate that in humans these cells suppress proliferation to self antigens, but also to dietary and foreign antigens. The suppressive CD4+CD25+ T cells display a broad usage of the T cell receptor Vbeta repertoire,suggesting that they recognize a wide variety of antigens. They reside in the primed/memory CD4+CD45RO+CD45RB(low) subset and have short telomeres, indicating that these cells have the phenotype of highly differentiated CD4+ T cells that have experienced repeated episodes of antigen-specific stimulation in vivo. This suggests that anergic/suppressive CD4+CD25+ T cells may be generated in the periphery as a consequence of repeated antigenic encounter. This is supported by the observation that highly differentiated CD4+T cells can be induced to become anergic/suppressive when stimulated by antigen presented by non-professional antigen-presenting cells. We suggest that besides being generated in the thymus, CD4+CD25+ regulatory T cells may also be generated in the periphery. This would provide a mechanism for the generation of regulatory cells that induce tolerance to a wide array of antigens that may not be encountered in the thymus.     

Neural substrates of coping behavior in the rat: possible importance of mesocorticolimbic dopamine system

This study measured expression of Fos protein, an indicator of neural activation, in 116 brain regions of rats that were able to control a stressor (i.e., avoid and/or escape an electric shock), and compared the changes with those observed in yoked rats that received the same shocks but without having control over them. The authors' interest was to find brain regions where elevated activity occurs in conjunction with control. Activity in these brain regions might be responsible for the consequences of having control, such as reduction of stress responses. Eleven brain regions were found in which rats with control showed significantly more Fos expression than was seen in yoked rats that did not have control. Six of these brain regions were part of the mesocorticolimbic dopamine system. These results point to the mesocorticolimbic dopamine system as being importantly involved in the mediation and/or the consequences of coping behavior.     

The effect of an intercollegiate soccer game on maximal power performance.

The effect of a competitive soccer match on maximal power performance was assessed on 19 members of an NCAA Division III female soccer team. Performance testing occurred within 24 hours prior to the game (Pre), immediately postgame (IP), and 24 hours postgame (24P). Each subject performed a squat jump (SJ) and countermovement jump (CMJ). Comparisons between starters (n = 10) and nonstarters (n = 9) revealed no between-group differences in power performance at IP, but starters were found to have significantly lower power and force measures at 24P than nonstarters. There were significant correlations between playing time and peak force during the SJ at 24P (r = -0.47), and between playing time and peak power during the SJ at IP (r = -0.57) and 24P (r = -0.51), and during the CMJ at IP (r = -0.49). Comparisons between different positions revealed no differential fatigue patterns. Results of this study show that power performance appears to be maintained for the duration of a soccer match but declines significantly within 24 hours after the match. Position played does not appear to affect performance decrements seen at 24 hours postmatch.     

Safety of cetirizine in infants 6 to 11 months of age: a randomized,double-blind,placebo-controlled study

BACKGROUND: H(1)-antihistamines are widely used for symptom relief in allergic disorders in infants and children; however, there are few prospective, randomized, double-blind, controlled studies of these medications in young children, and to date, no such studies have been conducted in infants. OBJECTIVE: This prospective, randomized, parallel-group, double-blind, placebo-controlled study was designed to evaluate the safety of the H(1)-antihistamine cetirizine, particularly with regard to central nervous system and cardiac effects, in infants age 6 to 11 months, inclusive. METHODS: Infants who met the entry criteria for age and had a history of treatment with an H(1)-antihistamine for an allergic or other disorder were randomized to receive 0.25 mg/kg cetirizine orally or matching placebo twice daily orally for 1 week. RESULTS: The mean daily dose in cetirizine-treated infants was 4.5 +/- 0.7 mg (SD). No differences in all-cause or treatment-related adverse events were observed between the cetirizine- and placebo-treated groups. A trend was observed toward fewer adverse events and sleep-related disturbances in the cetirizine group compared with the placebo group. No prolongation in the linear corrected QT interval was observed in cetirizine-treated infants compared with either baseline values or with values in placebo-treated infants. CONCLUSIONS: We have documented the safety of cetirizine in this short-term investigation, the first randomized, double-blind, placebo-controlled study of any H(1)-antihistamine in infants. Additional prospective, randomized, double-blind, placebo-controlled, long-term studies of cetirizine and other H(1)-antihistamines are needed in this population.     

HIV infection and associated risks among young men who have sex with men in a Florida resort community

OBJECTIVE: Several recent studies have reported high rates of sexual risk-taking and HIV infection among young men who have sex with men (MSM). Most of these studies used samples of convenience. The authors obtained population-based data on young MSM living in South Beach (Miami Beach, Florida), a resort community where some of the highest AIDS rates in the United States have been reported. METHODS: A household probability sample was drawn to survey unmarried 18- to 29-year-old MSM living in South Beach. Subjects were interviewed, completed self-administered questionnaires, and provided oral specimens for HIV antibody testing. RESULTS: From the 2,622 screened residential units, 100 mostly white and Hispanic MSM (92.6% of eligible participants) were enrolled in the study. Fifteen percent of the sample tested positive for antibodies to HIV. White and Hispanic MSM had similar rates. Forty-five percent of the sample reported engaging in unprotected anal intercourse (UAI) in the prior 12 months, and 31% reported UAI with a nonprimary partner. The estimated annual incidence of HIV infection was 6.3%. CONCLUSION: The high prevalences of UAI and HIV infection in South Beach attest to a previously undocumented public health concern. The extremely high estimated incidence for young MSM in South Beach highlights the urgent need for more effective risk-reduction interventions and further epidemiological research on resort areas.