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Short androgen receptor allele length is a poor prognostic factor in epithelial ovarian carcinoma.

PURPOSE: Epidemiological evidence implicates a heightened androgenic state in women with epithelial ovarian cancer. Androgen activity may be modulated by altered expression or activity of the androgen receptor (AR) or AR polymorphisms. Exon 1 of the AR gene contains a polymorphic (CAG)(n) sequence whose length is inversely correlated with transcriptional activity. EXPERIMENTAL DESIGN: Differential expression of AR mRNA and protein was examined in 46 primary cultures of normal human ovarian surface epithelium (HOSE) and malignant Cedars-Sinai ovarian cancer (CSOC) ovarian epithelial cells. AR allele length was characterized by genotyping in 77 ovarian cancer specimens. RESULTS: AR mRNA expression was higher in CSOC primary cultures (1.58 +/- 0.17) when compared with HOSE (1 +/- 0.09, P = 0.005), but protein expression was not statistically different. CAG repeat lengths were shorter in CSOC (20.6 +/- 1.2) than in HOSE (23.4 +/- 0.9, P = 0.04). Patients with an AR allele containing < or =19 CAG repeats had a shorter time to recurrence (5.5 versus 19.4 months, P < 0.0001) and overall survival (9 versus 32.6 months, P = 0.0007). There was no correlation between AR allelotype and age of diagnosis, stage, or grade; however, a short CAG length < or =19 repeats was associated with decreased surgical cytoreducibility (44.4 versus 10.3%, P = 0.035). Multivariate analyses confirmed a short AR allele as an independent prognostic factor (P = 0.02). CONCLUSIONS: These data support epidemiological evidence linking heightened androgenicity to the pathogenesis and tumor biology of epithelial ovarian cancer.

Alleles↗

Effects of high-top and low-top shoes on ankle inversion.

OBJECTIVE: To determine the differences in the rate and amount of ankle inversion in subjects wearing high-top and low-top shoes. DESIGN AND SETTING: Subjects were filmed at 60 Hz while on an inversion platform that suddenly inverted the right ankle 35 degrees . We measured 5 trials of sudden inversion for each subject in high-top and low-top shoes. SUBJECTS: Twenty male subjects with no history of lower leg injury within the previous 6 months. MEASUREMENTS: We measured ankle inversion using video motion analysis techniques at 60 Hz. A2 x 5 factorial repeated- measures analysis of variance was used to test for significant differences in the amount of inversion, average rate of inversion, and maximum rate of inversion. RESULTS: The high-top shoes significantly reduced the amount and rate of inversion. The high-top shoes reduced the amount of inversion by 4.5 degrees , the maximum rate of inversion by 100.1 degrees /s, and the average rate of inversion by 73.0 degrees /s. CONCLUSIONS: The high-top shoes were more effective in reducing the amount and rate of inversion than the low-top shoes. Depending upon the loading conditions, high-top shoes may help prevent some ankle sprains.

Journal Article↗

[Appearance on effort of an image of a sub-epicardial lesion in the absence of signs of myocardial necrosis. Clinical, electrocardiographic and coronographic studies of 10 cases].

A clinical, electrocardiographic and coronarographic study of ten cases shows that surelevation of ST-segment during exercise (without any signs of infarction) correspond to very different clinical situations of anatomical state of coronary vessels, occurrence of coronary spasm and evolution of the ischemic disease. "Inversed coronary Insufficiency" is proposed to design this syndrome. Practical recommandations are formulated.

Adult↗

[Prognostic factors in amyotrophic lateral sclerosis].

Survival in patients with amyotrophic lateral sclerosis is highly variable. In a prospective study of 71 patients, we analyzed the influence of several clinical factors on survival: age of onset, sex, initial involvement (bulbar, upper extremities or lower extremities) and familial history. Mean time of evolution was 2.6 years, with 25% survival 5 years after onset. Patients under 45 years old had better survival than those over 45 (5.8 and 2.2 years, respectively, p < 0.002). The prognosis for women was worse (2.07 and 3.6 years for women and men, respectively, p < 0.001), probably because age of onset was later in women (61 versus 53 years, respectively, p < 0.006). Neither first symptom or familial history of the disease affected prognosis. We conclude that age at onset is a decisive prognostic factor that is inversely related to survival. In the design of clinical trials in which survival is a variable, the treatment and control groups should be matched for age.

Adult↗

Plasma xanthophyll carotenoids correlate inversely with indices of oxidative DNA damage and lipid peroxidation.

Post hoc analysis of data obtained from a study designed to modulate oxidative damage by dietary intervention revealed consistently strong inverse correlations between plasma xanthophyll carotenoids and oxidative damage indices. Thirty-seven women participated in a 14-day dietary intervention that increased mean vegetable and fruit (VF) consumption to approximately 12 servings/day. An additional 10 subjects participated in an intervention that limited VF consumption to less than four servings per day. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) in DNA isolated from peripheral lymphocytes and 8-OHdG excreted in urine were measured as indices of oxidative DNA damage. Lipid peroxidation was assessed by measuring 8-epiprostaglandin F2alpha (8-EPG) in urine. Plasma levels of selected carotenoids were also determined, with the intention of using a-carotene as a biochemical index of VF consumption. Urinary 8-OHdG and 8-EPG were measured by ELISA, and plasma carotenoids were measured by high performance liquid chromatography. Lymphocyte 8-OHdG was measured by reverse phase high performance liquid chromatography with electrochemical detection. We observed that the structurally related xanthophyll carotenoids, lutein and beta-cryptoxanthin, which occur in dissimilar botanical families, were consistently inversely associated with these oxidative indices. Statistically significant inverse correlations were observed between plasma lutein and/or beta-cryptoxanthin levels and lymphocyte 8-OHdG and urinary 8-EPG. Moreover, an inverse correlation was observed between change in plasma xanthophylls and change in lymphocyte 8-OHdG concentration that occurred during the course of the study. These data lead us to hypothesize that lutein and beta-cryptoxanthin serve as markers for the antioxidant milieu provided by plants from which they are derived. Whether these carotenoids are directly responsible for the observed antioxidant phenomena merits further investigation.

8-Hydroxy-2'-Deoxyguanosine↗

Sequence-specific, self-reporting hairpin inversion probes.

Sequence-specific probes for detecting target nucleic acids are the cornerstone of the genomics revolution (e.g., microarrays) and of molecular diagnostics. Molecular beacons are self-reporting, nucleic acid probes whose structure includes complementary terminal arm sequences and a loop that is complementary to a target sequence; fluorescence detection is by changes in proximity of fluorophore and quencher pairs attached on opposite arms. However, molecular beacon design is not as simple as attaching arbitrary arm sequences onto previously designed linear probes. The stem arms can also interact with flanking target sequences, changing the hybridization specificity; constantly adapting the arms to avoid such interactions, if not desired, increases design complexity. Herein, I report the use of inversion linkages in probe backbones leading to stem arms of sequence polarity opposite to that of the target-binding region, thereby eliminating potential hybridization of the arms with the target. Using two microbial sequence categories, thermal denaturation and target titration analyses demonstrate that these new hairpin inversion probes retain closed-state stability comparable to that of molecular beacons, contain easily designed arm sequences that do not interact with targets, and, therefore, can be used universally with optimized linear probe sequences.

Base Sequence↗

An independent, inverse association of high-density-lipoprotein-cholesterol concentration with nonadipose body mass.

BACKGROUND: Increasing body mass index (BMI) is associated with progressively lower serum HDL-cholesterol concentrations, although the underlying body-composition compartment accounting for this unfavorable lipid change remains uncertain. OBJECTIVE: Because growing evidence favors a role of lean tissue in HDL homeostasis, the hypothesis was tested that non-adipose tissue components of body mass explain the inverse association of HDL cholesterol and BMI. DESIGN: Fasting serum lipid concentrations and body composition [total, subcutaneous, and visceral adipose tissue; adipose tissue-free mass (ATFM); and skeletal muscle by whole-body magnetic resonance imaging and body cell mass by 40K counting) were evaluated in healthy adults. Body-composition compartments were expressed as height2-normalized indexes. RESULTS: An inverse correlation was observed between serum HDL cholesterol and BMI in women (n = 68; R2 = 0.08, P = 0.023) and men (n = 61; R2 = 0.07, P = 0.046). Significant inverse correlations (P = 0.005-0.02) were also observed between HDL cholesterol and nonadipose components (ie, ATFM, skeletal muscle, and body cell mass) but not between HDL cholesterol and any adipose tissue component. The association between HDL cholesterol and ATFM remained significant after serum triacylglycerol was controlled for. When BMI was entered into the HDL cholesterol-ATFM regression model, BMI was not a significant independent variable. The strongest correlate of serum triacylglycerol was visceral adipose tissue (P = 0.002 for both women and men). CONCLUSIONS: Lean tissues and body cell mass appear to account in part for the long-observed inverse association of HDL cholesterol and BMI. These observations suggest a link between nonadipose tissue compartments and the greater cardiovascular risk associated with high BMI.

Adipose Tissue↗

Cone-beam reconstruction using the backprojection of locally filtered projections.

This paper describes a flexible new methodology for accurate cone beam reconstruction with source positions on a curve (or set of curves). The inversion formulas employed by this methodology are based on first backprojecting a simple derivative in the projection space and then applying a Hilbert transform inversion in the image space. The local nature of the projection space filtering distinguishes this approach from conventional filtered-backprojection methods. This characteristic together with a degree of flexibility in choosing the direction of the Hilbert transform used for inversion offers two important features for the design of data acquisition geometries and reconstruction algorithms. First, the size of the detector necessary to acquire sufficient data for accurate reconstruction of a given region is often smaller than that required by previously documented approaches. In other words, more data truncation is allowed. Second, redundant data can be incorporated for the purpose of noise reduction. The validity of the inversion formulas along with the application of these two properties are illustrated with reconstructions from computer simulated data. In particular, in the helical cone beam geometry, it is shown that 1) intermittent transaxial truncation has no effect on the reconstruction in a central region which means that wider patients can be accommodated on existing scanners, and more importantly that radiation exposure can be reduced for region of interest imaging and 2) at maximum pitch the data outside the Tam-Danielsson window can be used to reduce image noise and thereby improve dose utilization. Furthermore, the degree of axial truncation tolerated by our approach for saddle trajectories is shown to be larger than that of previous methods.

Algorithms↗

Improved efficiency in double-inversion fast spin-echo imaging.

Double-inversion fast spin-echo (FSE) pulse sequences can be designed to provide excellent suppression of blood signal in black-blood MRI. However, because a nonselective inversion is used, these sequences typically have been highly inefficient. In this work it is demonstrated that the efficiency of double-inversion sequences can be greatly improved by a form of interleaving in which all of the slices to be imaged in a single pass are reinverted each time a signal is obtained from any single slice. To date, several studies have demonstrated a high level of blood suppression with these more efficient techniques.

Aged↗

Production of nitric oxide by murine bone marrow cells. Inverse correlation with cellular proliferation.

The present studies were designed to assess the ability of primary cultures of bone marrow cells to produce nitric oxide. We found that two inflammatory stimuli, IFN-gamma and LPS, were potent inducers of nitric oxide production by bone marrow cells. In addition, the CSF granulocyte-macrophage (GM)-CSF and IL-3 as well as TNF-alpha, while inactive by themselves, were synergistic with LPS and IFN-gamma in inducing nitric oxide production. Maximal effects were observed with combinations of GM-CSF and LPS. Nitric oxide production by bone marrow cells was found to be dependent on the presence of L-arginine in the culture medium and inhibitable by NG-monomethyl-L-arginine and L-canavanine, two nitric oxide synthase inhibitors. Nitric oxide produced by the cells was also suppressed by TGF-beta 1 and the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate. Separation of bone marrow cells by density gradient centrifugation and flow cytometry revealed that the granulocyte-containing fraction was largely responsible for nitric oxide production. In additional experiments we found that treatment of bone marrow cells with GM-CSF significantly stimulated bone marrow cell growth. In contrast, the combination of GM-CSF and LPS or IFN-gamma markedly suppressed cellular proliferation. This suppression was completely reversed by treatment of the cells with NG-monomethyl-L-arginine. Taken together, these data demonstrate that various inflammatory stimuli and cytokines induce nitric oxide production by primary cultures of bone marrow cells and that this mediator may play a role in the regulation of bone marrow cell growth and development.

Animals↗

Regulation of a restriction and modification system via DNA inversion in Mycoplasma pulmonis.

An invertible DNA element of 6.8 kb, designated the hsd1 locus, was identified in the chromosome of Mycoplasma pulmonis. Infection of host cells with mycoplasma virus P1 revealed that the organism's restriction and modification (R-M) properties are controlled by inversion of hsd1. The nucleotide sequence of hsd1 revealed several genes, the predicted amino acids of which bear striking similarity to the subunits of the type I R-M enzymes previously found only in enteric bacteria.

Amino Acid Sequence↗

Meta-analysis of antibiotics for the treatment of otitis media with effusion.

OBJECTIVE: To reconcile conflicting reports of antibiotic efficacy for otitis media with effusion in children. DATA SOURCES: English-language MEDLINE search ("antibiotics" and "otitis" media with effusion") from January 1980 through December 1990. Current Contents 1990, consultation with experts, and references from review articles, textbook chapters, and retrieved reports. STUDY SELECTION: Randomized clinical trials with concurrent controls (placebo or no drug), and children with at least one ear not violated by tympanocentesis. Ten of the initial 82 articles were selected after blind review of the methods sections. DATA EXTRACTION: We independently evaluated each trial using 20 measures of internal and external validity, then extracted treatment and control responses for an end point of all affected ears free of effusion at the first posttreatment assessment. DATA SYNTHESIS: Pooled analysis of 1325 children yielded a rate difference of 22.8% (95% Cl, 10.5 to 35.1) that was minimally affected by interstudy quality differences, and was unlikely to represent publication bias. Variations in trial outcomes were not attributable to chance, study design, or choice of drug, but were inversely related to the control group natural cure rate. Children with chronic bilateral effusions not related to a recent episode of acute otitis media tended to have lower natural cure rates, and a more favorable response to therapy. CONCLUSIONS: Antibiotics have a clinically and statistically significant impact on the resolution of otitis media with effusion. The association between outcome and natural cure rate has important implications for the design and interpretation of future trials.

Anti-Bacterial Agents↗

Evaluation of a FLAIR sequence designed to reduce CSF and blood flow artifacts by use of k-space reordered by inversion time at each slice position (KRISP) in high grade gliomas of the brain.

The objective of this study was to compare conventional and KRISP (k-space reordered by inversion time at each slice position) fluid-attenuated inversion recovery (FLAIR) sequences in high grade gliomas for artifact control, conspicuity of intracranial structures, and lesions as well as sensitivity to contrast enhancement. Artifacts were lower with the KRISP FLAIR sequence, and the conspicuity of all assessed structures and lesions was better. The degree of contrast enhancement was similar with T1-weighted and KRISP FLAIR sequences.

Adult↗

A spectral clustering approach to underdetermined postnonlinear blind source separation of sparse sources.

This letter proposes a clustering-based approach for solving the underdetermined (i.e., fewer mixtures than sources) postnonlinear blind source separation (PNL BSS) problem when the sources are sparse. Although various algorithms exist for the underdetermined BSS problem for sparse sources, as well as for the PNL BSS problem with as many mixtures as sources, the nonlinear problem in an underdetermined scenario has not been satisfactorily solved yet. The method proposed in this letter aims at inverting the different nonlinearities, thus reducing the problem to linear underdetermined BSS. To this end, first a spectral clustering technique is applied that clusters the mixture samples into different sets corresponding to the different sources. Then, the inverse nonlinearities are estimated using a set of multilayer perceptrons (MLPs) that are trained by minimizing a specifically designed cost function. Finally, transforming each mixture by its corresponding inverse nonlinearity results in a linear underdetermined BSS problem, which can be solved using any of the existing methods.

Algorithms↗

Changes in pulmonary mechanics and gas exchange after thoracentesis on patients with inversion of a hemidiaphragm secondary to large pleural effusion.

The present study was designed to test whether there was a significant improvement in pulmonary function and arterial blood oxygenation after therapeutic thoracentesis on patients with inversion of a hemidiaphragm due to pleural effusion. In 21 patients with inversion of a hemidiaphragm because of a pleural effusion, we studied the changes in pulmonary mechanics and gas exchange that occurred in 24 h after removal of 600 to 2,700 mL of fluid by thoracentesis. There was a small but significant increase in the forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) (p < 0.001). The alveolar-arterial oxygen gradient (P[A-a]O2) and partial pressure of arterial oxygen (PaO2) showed a significant increase (p < 0.001), but there was no change in partial pressure of arterial carbon dioxide (PaCO2). In the present study, all patients with a large pleural effusion had inversion of a hemidiaphragm documented by chest sonography, and that was an important factor to observe significant improvement in pulmonary mechanics and gas exchange.

Adult↗

Atopic dermatitis and the 'hygiene hypothesis': too clean to be true?

BACKGROUND: The so-called 'hygiene hypothesis' postulates an inverse relationship between atopic dermatitis (AD) and an environment that leads to increased pathogen exposure. OBJECTIVES: We sought to systematically identify, summarize and critically appraise: (i) the epidemiological evidence to suggest that environmental exposures that lead to an increase in microbial burden reduce the risk of AD; (ii) whether any specific infections have been shown to reduce AD risk; (iii) whether there is a link between immunizations, use of antibiotics and AD risk; and (iv) to comment on the new therapeutic approaches in AD that have evolved out of the 'hygiene hypothesis'. METHODS: We searched Medline from 1966 until August 2004 to identify relevant studies for inclusion. Differences in study design and populations did not allow formal meta-analysis. Studies were therefore described qualitatively. RESULTS: We identified 64 studies that were relevant to our review, 27 (42%) of which were of prospective design. There was prospective evidence to support an inverse relationship between AD and endotoxins, early day care and animal exposure. Two well-designed cohort studies have found a positive association between infections in early life and AD, and measles vaccination and AD. Antibiotic use was consistently associated with an increase in AD risk even into the antenatal period, although a few studies did not reach conventional statistical significance. A few small randomized controlled trials have suggested that probiotics can reduce AD severity and that probiotics may also be able to prevent AD to some degree. CONCLUSIONS: Although population-based studies have suggested a consistent inverse relationship between AD and increasing family size, this does not seem to be explained by a straightforward increased exposure to a single environmental pathogen. The effect seen with early day care, endotoxin and animal exposure may be due to a nonpathogenic microbial stimulus of a chronic or recurrent nature. This would also explain the risk increase associated with antibiotic use. Caution should prevail in the prescribing of antibiotics early in life, especially in children with a family history of AD. Larger well-designed pragmatic trials on probiotics and the prevention and treatment of AD are now needed to inform whether such interventions should be used in routine clinical practice.

Adolescent↗

Robust optimal design for the estimation of hyperparameters in population pharmacokinetics.

The expectation of the determinant of the inverse of the population Fisher information matrix is proposed as a criterion to evaluate and optimize designs for the estimation of population pharmacokinetic (PK) parameters. Given a PK model, a measurement error model, a parametric distribution of the parameters and a prior distribution representing the belief about the hyperparameters to be estimated, the EID criterion is minimized in order to find the optimal population design. In this approach, a group is defined as a number of subjects to whom the same sampling schedule (i.e., the number of samples and their timing) is applied. The constraints, which are defined a priori, are the number of groups, the size of each group and the number of samples per subject in each group. The goal of the optimization is to determine the optimal sampling times in each group. This criterion is applied to a one-compartment open model with first-order absorption. The error model is either homoscedastic or heteroscedastic with constant coefficient of variation. Individual parameters are assumed to arise from a lognormal distribution with mean vector M and covariance matrix C. Uncertainties about the M and C are accounted for by a prior distribution which is normal for M and Wishart for C. Sampling times are optimized by using a stochastic gradient algorithm. Influence of the number of different sampling schemes, the number of subjects per sampling schedule, the number of samples per subject in each sampling scheme, the uncertainties on M and C and the assumption about the error model and the dose have been investigated.

Humans↗