The peroxisome proliferator-activated receptor gamma coactivator-1 alpha gene (PGC-1alpha) is not associated with type 2 diabetes mellitus or body mass index among Hispanic and non Hispanic Whites from Colorado.

The objective of the study was to test for an association between type 2 diabetes mellitus (T2DM) and body mass index (BMI) and three single nucleotide polymorphisms (SNP)s in the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1alpha) gene. We were also interested in whether these associations differed by tertiles of diet, physical activity or presence of polymorphisms in the peroxisome proliferator-activated receptor gamma (PPAR-gamma) gene among Hispanics and Non-Hispanic Whites (NHW) from Colorado. We studied 216 Hispanic pedigrees (1850 nuclear families) and 236 NHW pedigrees (1240 families) from the San Luis Valley and Denver. We genotyped the Gly482Ser, Thr528Thr and Thr612Met polymorphisms in the PGC-1alpha gene and the Pro12Ala polymorphism of the PPAR-gamma gene. Historical physical activity (average METS/week) as well as average dietary intake over the past year was assessed by self-report. Data were analyzed using the Family Based Association Test (FBAT) as well as generalized estimating equations (GEE). We did not find any significant association between three SNPs in the PGC-1alpha gene and T2DM in Hispanics or NHW; however, using FBAT, we found the common Thr612Thr allele of the PGC-1alpha gene to be associated with T2DM among Hispanic subjects carrying the rare Pro12Ala allele of the PPAR-gamma gene (p=.003). We found similar associations when we considered a haplotype containing that allele (p=.002). However, the results of the GEE analysis did not confirm these findings: odds ratio (OR)=1.68, 95% CI (0.5, 5.2) suggesting these results may due to chance. BMI also did not show any consistent associations with the PGC-1alpha gene. In conclusion, we did not find an association between the PGC-1alpha gene and T2DM or BMI and there were no consistent interactions with diet, physical activity or the Pro12Ala polymorphism of the PPAR-gamma gene.     

Looking for resilience: Understanding the longitudinal trajectories of responses to stress

Taking advantage of two large, population-based, and longitudinal datasets collected after the 1999 floods in Mexico (n = 561) and the September 11, 2001 terrorist attacks in New York (n = 1267), we examined the notion that resilience may be best understood and measured as one member of a set of trajectories that may follow exposure to trauma or severe stress. We hypothesized that resistance, resilience, recovery, relapsing/remitting, delayed dysfunction, and chronic dysfunction trajectories were all possible in the aftermath of major disasters. Semi-parametric group-based modeling yielded the strongest evidence for resistance (no or mild and stable symptoms), resilience (initially moderate or severe symptoms followed by a sharp decrease), recovery (initially moderate or severe symptoms followed by a gradual decrease), and chronic dysfunction (moderate or severe and stable symptoms), as these trajectories were prevalent in both samples. Neither Mexico nor New York showed a relapsing/remitting trajectory, and only New York showed a delayed dysfunction trajectory. Understanding patterns of psychological distress over time may present opportunities for interventions that aim to increase resilience, and decrease more adverse trajectories, after mass traumatic events.     

Selective parity RARE imaging.

This work describes a novel method for rapid acquisition with relaxation enhancement (RARE)/fast spin-echo (FSE) imaging that removes the constraint of compliance with the Carr-Purcell-Meiboom-Gill (CPMG) condition. In a multiecho sequence, echoes with either odd or even parities are acquired. The refocusing angles are chosen using a recursive algorithm, so that the signal amplitude satisfies a predetermined modulation function. In the examples given in this article an exponential decay to a plateau is used. At each echo the echo parity that gives the desired signal amplitude for the minimum refocusing angle is selected. It is further shown that in the presence of an initial magnetization having an arbitrary phase distribution, the complex conjugate of the signal of one echo parity has to be taken and its k-space coordinates reversed. T(2) (*)-weighted images are presented and initial applications to diffusion-weighted imaging (DWI) and functional imaging shown.     

Silent ischemia in rehabilitation patients: limited clinical utility of electrocardiographic monitoring.

In a prospective blinded trial, 24-hour continuous electrocardiographic monitoring for silent ischemia was used to try to identify rehabilitation patients at risk for cardiac complications. Five of 42 patients had episodes of silent ischemia, none of which occurred during physical therapy sessions. One of these patients had syncope while wearing the Holter; none of the other four patients had significant cardiac complications during their rehabilitation, and all were discharged home. None of the patients without ischemia on the monitor had complications, but two patients of 14 whose ECGs precluded monitoring for ischemia had complications. In addition, six patients had episodes of nonsustained asymptomatic ventricular tachycardia, 12 had episodes of supraventricular tachycardia, and four had significant ventricular ectopy, all without clinical significance. Despite the apparent high sensitivity and specificity of the technique, the positive predictive value of monitoring eligible patients for silent ischemia was 20%. We conclude that ambulatory electrocardiographic monitoring for silent ischemia or ectopy has limited clinical utility in the rehabilitation population.     

Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

Activation of guinea pig eosinophil respiratory burst by leukotriene B4: role of protein kinase C

Leukotriene B4 (LTB4) and the protein kinase C activator, 4-beta-phorbol dibutyrate (PDBu), both induced a pronounced and concentration-dependent stimulation of hydrogen peroxide (H2O2) generation by purified guinea pig peritoneal eosinophils in the concentration range 1 nM-1 microM. The LTB4 response was inhibited competitively by the specific LTB4 receptor antagonist, U-75302, with a KB of 25 nM, while the concentration-response curves for both stimuli were shifted rightwards (3.8-fold and 2.8-fold for LTB4 and PDBu, respectively) by the competitive protein kinase C inhibitor, 1-O-hexadecyl-2-O-methylglycerol at a concentration of 300 microM. LTB4 appears, therefore, to induce respiratory burst in eosinophils via a receptor-mediated mechanism involving protein kinase C.     

Quantifying the intra- and extravascular contributions to spin-echo fMRI at 3 T.

Functional MRI (fMRI) by means of spin-echo (SE) techniques provides an interesting alternative to gradient-echo methods because the contrast is based primarily on dynamic averaging associated with the blood oxygenation level-dependent (BOLD) effect. In this article the contributions from different brain compartments to BOLD signal changes in SE echo planar imaging (EPI) are investigated. To gain a better understanding of the underlying mechanisms that cause the fMRI contrast, two experiments are presented: First, the intravascular contribution is decomposed into two fractions with different regimes of flow by means of diffusion-weighting gradient schemes which are either flow-compensated, or will maximally dephase moving spins. Second, contributions from the intra- and extravascular space are selectively suppressed by combining flow-weighting with additional refocusing pulses. The results indicate two qualitatively different components of flowing blood which contribute to the BOLD contrast and a nearly equal share in functional signal from the intra- and extravascular compartments at TE approximately 80 ms and 3 T. Combining these results, there is evidence that at least one-half of the functional signal originates from the parenchyma in SE fMRI at 3 T. The authors suggest the use of flow-compensated diffusion weighting for SE fMRI to improve the sensitivity to the parenchyma.