Atherosclerotic plaque components in human aortas contrasted by ex vivo imaging using fast spin-echo magnetic resonance imaging and spiral computed tomography

RATIONALE AND OBJECTIVES: Imaging techniques that distinguish atherosclerotic plaque components may be useful in identifying the nature of the atherosclerotic lesion and determining the best method of treatment for obstructive vascular mining the best method of treatment for obstructive vascular disease. This study compares fast spin-echo (FSE) magnetic resonance (MR) and spiral computed tomography (CT) images of excised human atherosclerotic aortas to determine which imaging technique provides the best contrast between plaque components ex vivo. METHODS: Aortas were imaged using four FSE sequences in MR with and without frequency-selective fat saturation, and using spiral CT without contrast. The average signal intensity of a region of calcification, thrombosis, fatty plaque, and normal vessel wall was measured on all images and compared. RESULTS: The use of fat saturation pulses in MR did not significantly alter the signal from atherosclerotic plaque for the sequences used. Proton density-weighted FSE sequences that collected early echoes were better than other FSE sequences and CT at differentiating calcification from all soft tissues. T2-weighted FSE sequences that collected later echoes were best at soft-tissue discrimination. CONCLUSIONS: The FSE techniques used were superior to nonenhanced spiral CT in discriminating plaque components ex vivo, including calcification.     

Does collecting repeated blood samples from each subject improve the precision of estimated steroid hormone levels?

Peripheral blood mononuclear cells were isolated from noninfected control cows and from cows with either subclinical or clinical paratuberculosis (Johne's disease). Cells were incubated for 6, 12, 24, and 48 hours in complete medium with the following mitogens: concanavalin A (ConA), phytohemagglutinin-P (PHAP), pokeweed mitogen (PWM), and Escherichia coli lipopolysaccharide. In addition, cells were incubated for the same time periods with a Mycobacterium paratuberculosis sonicate (MpS) and live and heat-killed M. paratu-berculosis at 10:1 bacteria: cell ratio. After incubation, cell-free supernatants were analyzed for gamma-interferon (gamma-IFN) production. Cells from subclinical cows produced significantly higher levels of gamma-IFN than did cells from clinical animals after stimulation with mitogens ConA, PHAP, and PWM. Levels of gamma-IFN produced by noninfected control animals generally followed the pattern of those of subclinical animals. After incubation with MpS, significantly greater quantities of gamma-IFN were produced by cells isolated from subclinical animals than by cells from clinical cows and noninfected controls. Stimulation of cells with heat-killed or live M. paratuberculosis evoked a similar response. This study indicates that gamma-IFN production by peripheral blood mononuclear cells in response to M. paratuberculosis antigen may be an important diagnostic tool for the detection of paratuberculosis in subclinically affected animals.     

Social physique anxiety in postmenopausal women

Social physique anxiety (SPA), the degree to which individuals become anxious when others observe their bodies, is an important concept for postmenopausal women because it may be directly related to their physical activity behavior. Women with high levels of social physique anxiety may not participate in health-enhancing physical activity. Therefore, the main purpose of this study was to examine SPA in postmenopausal women relative to leisure time physical activity (LTPA, activities such as exercise, recreation, and sports). Other factors, such as percent body fat, body fat distribution, age, and hormone replacement therapy status were also examined for their relationship to SPA. Women who expended < or = 500 kcal.wk-1 in LTPA had significantly higher SPA than women who expended > or = 2,000 kcal.wk-1, independent of percent body fat. Women with more than 37.5% body fat had significantly higher SPA than those with less than 37.5% body fat. Women with upper BFD (waist-to-hip ratio or WHR > 0.85) had higher SPA than women with lower BFD (WHR < 0.75). There were no differences in SPA relative to age or HRT status. It appears that a sedentary lifestyle, high percent body fat, and upper body fat distribution are associated with increased SPA in postmenopausal women, thus health promotion professionals should be aware of these concerns when developing physical activity interventions for postmenopausal women.     

Randomised trial of nitric oxide donor versus prostaglandin for cervical ripening before first-trimester termination of pregnancy

BACKGROUND: Vaginal administration of the nitric oxide donor isosorbide mononitrate can induce effective ripening of the human cervix. We investigated whether this drug is associated with fewer side-effects than prostaglandins when used to ripen the cervix before first-trimester surgical termination of pregnancy, and assessed whether the extent of cervical ripening it induces is clinically sufficient. METHODS: 66 primigravid women scheduled for surgical termination were assigned to receive before surgery, per vaginam, isosorbide mononitrate 40 mg or 80 mg, or the prostaglandin analogue gemeprost 1 mg. The primary measured outcome was onset of new symptoms before termination of pregnancy. FINDINGS: More women remained symptom-free after isosorbide mononitrate than after gemeprost (28/44 [64%] vs 3/22 [14%], p<0.005). Pretreatment with gemeprost resulted in abdominal pain in 73% of women and vaginal bleeding in 32% compared with 3% and 0%, respectively, after isosorbide mononitrate, whereas, more women developed headache after isosorbide mononitrate (27%) than after gemeprost (0%). Cervical resistance and measured intraoperative blood loss were lowest after pretreatment with gemeprost. The measured cervical resistance and intraoperative blood loss with either dose of isosorbide mononitrate did not differ from those in a comparison group of 22 parous women not in the randomised trial. INTERPRETATION: Pretreatment with isosorbide mononitrate to ripen the cervix before first-trimester termination of pregnancy is associated with fewer side-effects than gemeprost treatment and adequately decreases cervical resistance. Isosorbide mononitrate could be used as an alternative to gemeprost for this indication.     

Gender and neurogenic variables in tendon biology and repetitive motion disorders

The incidence of repetitive motion disorders is increasing. Numerous studies have indicated that the incidence in females exceeds that in males. Some of the evidence regarding gender related factors in tendon biology is discussed and new data related to the regulation of gene expression in an animal model of tendon overuse, the determination of sex hormone receptors in tendons, and the influence of pregnancy associated factors on gene expression in four different tendons is provided. Furthermore, because neurogenic mechanisms may contribute to inflammatory conditions, new evidence is provided that supports the concept that neurotransmitters can influence expression of genes that could participate in such inflammation. By increasing our understanding of the regulation of tendon cellular and molecular biology, new approaches to preventing disease development and treatment of existing disease may evolve.     

Mutation of cysteine 111 in Dopa decarboxylase leads to active site perturbation

Cysteine 111 in Dopa decarboxylase (DDC) has been replaced by alanine or serine by site-directed mutagenesis. Compared to the wild-type enzyme, the resultant C111A and C111S mutant enzymes exhibit Kcat values of about 50% and 15%, respectively, at pH 6.8, while the K(m) values remain relatively unaltered for L-3,4-dihydroxyphenylalanine (L-Dopa) and L-5-hydroxytryptophan (L-5-HTP). While a significant decrease of the 280 nm optically active band present in the wild type is observed in mutant DDCs, their visible co-enzyme absorption and CD spectra are similar to those of the wild type. With respect to the wild type, the Cys-111-->Ala mutant displays a reduced affinity for pyridoxal 5'-phosphate (PLP), slower kinetics of reconstitution to holoenzyme, a decreased ability to anchor the external aldimine formed between D-Dopa and the bound co-enzyme, and a decreased efficiency of energy transfer between tryptophan residue(s) and reduced PLP. Values of pKa and pKb for the groups involved in catalysis were determined for the wild-type and the C111A mutant enzymes. The mutant showed a decrease in both pK values by about 1 pH unit, resulting in a shift of the pH of the maximum velocity from 7.2 (wild-type) to 6.2 (mutant). This change in maximum velocity is mirrored by a similar shift in the spectrophotometrically determined pK value of the 420-->390 nm transition of the external aldimine. These results demonstrate that the sulfhydryl group of Cys-111 is catalytically nonessential and provide strong support for previous suggestion that this residue is located at or near the PLP binding site (Dominici P, Maras B, Mei G, Borri Voltattorni C. 1991. Eur J Biochem 201:393-397). Moreover, our findings provide evidence that Cys-111 has a structural role in PLP binding and suggest that this residue is required for maintenance of proper active-site conformation.