Purification and partial characterization of two biologically active compounds from the inflorescence of Sauromatum guttatum Schott (Araceae)

The active principle triggering the metabolic outburst of theappendices of certain arum lily species has been purified andpartially characterized. Although in the past it has been thoughtof as a single factor ("calorigen"), both paper chromatographyand DEAE-Sephadex ion exchange chromatography reveal that thereare two compounds (calorigen I and II) with calorigen activity.These can act alone or together, but show no synergism. Theyare low-molecular compounds which appear to be common constituentsof the inflorescence of Sauromatum guttatum Schott. CalorigenII is also present in the spadix of Arum maculatum L., Arumdioscoridis Sibth. & Sm., and Dracunculus vulgaris Schott.Calorigen I absorbs UV at 242, 267 and 278 nm, calorigen IIat 229 and 295 nm. No spectral changes are noted in alkalineenvironment, whereas at low pH-values there is a shift of theabsorption peaks of both compounds towards longer wavelengths.Calorigen II displays a strong blue fluorescence and has a maximalemission at 410 nm when activated at 295 nm. The possible mechanismof calorigen action is discussed. ¹ Present address: Department of Biochemistry, University ofWashington, Seattle, Washington 98195, U.S.A. (Received August 26, 1974; )     

In vivo MR imaging of pulmonary perfusion and gas exchange in rats via continuous extracorporeal infusion of hyperpolarized 129Xe

Background

Hyperpolarized (HP) ¹²⁹Xe magnetic resonance imaging (MRI) permits high resolution, regional visualization of pulmonary ventilation. Additionally, its reasonably high solubility (>10%) and large chemical shift range (>200 ppm) in tissues allow HP ¹²⁹Xe to serve as a regional probe of pulmonary perfusion and gas transport, when introduced directly into the vasculature. In earlier work, vascular delivery was accomplished in rats by first dissolving HP ¹²⁹Xe in a biologically compatible carrier solution, injecting the solution into the vasculature, and then detecting HP ¹²⁹Xe as it emerged into the alveolar airspaces. Although easily implemented, this approach was constrained by the tolerable injection volume and the duration of the HP ¹²⁹Xe signal.

Methods and Principal Findings

Here, we overcome the volume and temporal constraints imposed by injection, by using hydrophobic, microporous, gas-exchange membranes to directly and continuously infuse ¹²⁹Xe into the arterial blood of live rats with an extracorporeal (EC) circuit. The resulting gas-phase ¹²⁹Xe signal is sufficient to generate diffusive gas exchange- and pulmonary perfusion-dependent, 3D MR images with a nominal resolution of 2×2×2 mm³. We also show that the ¹²⁹Xe signal dynamics during EC infusion are well described by an analytical model that incorporates both mass transport into the blood and longitudinal relaxation.

Conclusions

Extracorporeal infusion of HP ¹²⁹Xe enables rapid, 3D MR imaging of rat lungs and, when combined with ventilation imaging, will permit spatially resolved studies of the ventilation-perfusion ratio in small animals. Moreover, EC infusion should allow ¹²⁹Xe to be delivered elsewhere in the body and make possible functional and molecular imaging approaches that are currently not feasible using inhaled HP ¹²⁹Xe.     

Modulation of FcgammaRI (CD64) ligand binding by blocking peptides of periplakin

FcgammaRI requires both the intracellular domain of the alpha-chain and associated leukocyte Fc receptor (FcR) gamma-chains for its biological function. We recently found the C terminus of periplakin to selectively interact with the cytoplasmic domain of the FcgammaRI alpha-chain. It thereby enhances the capacity of FcgammaRI to bind, internalize, and present antigens on MHC class II. Here, we characterized the domains involved in FcgammaRI-periplakin interaction using truncated and alanine-substituted FcgammaRI mutants and randomly mutagenized periplakin. This allowed us to design TAT peptides that selectively interfered with endogenous FcgammaRI-periplakin interactions. The addition of these peptides to FcgammaRI-expressing cells modulated FcgammaRI ligand binding, as assessed by erythrocyte-antibody-rosetting. These data support a dominant-negative role of C-terminal periplakin for FcgammaRI biological activity and implicate periplakin as a novel regulator of FcgammaRI in immune cells.     

High-Sensitivity Cardiac Troponin Concentrations in Patients with Chest Discomfort: Is It the Heart or the Kidneys As Well?

BackgroundHigh-sensitivity cardiac troponins (hs-cTn) are the preferred biomarkers to detect myocardial injury, making them promising risk-stratifying tools for patients with symptoms of chest pain. However, circulating hs-cTn are also elevated in other conditions like renal dysfunction, complicating appropriate interpretation of low-level hs-cTn concentrations.MethodsA cross-sectional analysis was performed in 1864 patients with symptoms of chest discomfort from the cardiology outpatient department who underwent cardiac computed tomographic angiography (CCTA). Serum samples were analyzed using hs-cTnT and hs-cTnI assays. Renal function was measured by the estimated glomerular filtration rate (eGFR), established from serum creatinine and cystatin C. On follow-up, the incidence of adverse events was assessed.ResultsMedian hs-cTnT and hs-cTnI concentrations were 7.2(5.8–9.2) ng/L and 2.6(1.8–4.1) ng/L, respectively. Multivariable regression analysis revealed that both assay results were more strongly associated with eGFR (hs-cTnT:stβ:-0.290;hs-cTnI:stβ:-0.222) than with cardiac imaging parameters, such as coronary calcium score, CCTA plaque severity score and left ventricular mass (all p<0.01). Furthermore, survival analysis indicated lower relative risks in patients with normal compared to reduced renal function for hs-cTnT [HR(95%CI), 1.02(1.00–1.03) compared to 1.07(1.05–1.09)] and hs-cTnI [1.01(1.00–1.01) compared to 1.02(1.01–1.02)] (all p<0.001).ConclusionIn patients with chest discomfort, we identified an independent influence of renal function on hs-cTn concentrations besides CAD, that affected the association of hs-cTn concentrations with adverse events. Estimating renal function is therefore warranted when interpreting baseline hs-cTn concentrations.     

Glutamate as chemotactic fuel for diffuse glioma cells: Are they glutamate suckers?

Diffuse gliomas comprise a group of primary brain tumors that originate from glial (precursor) cells and present as a variety of malignancy grades which have in common that they grow by diffuse infiltration. This phenotype complicates treatment enormously as it precludes curative surgery and radiotherapy. Furthermore, diffusely infiltrating glioma cells often hide behind a functional blood–brain barrier, hampering delivery of systemically administered therapeutic and diagnostic compounds to the tumor cells. The present review addresses the biological mechanisms that underlie the diffuse infiltrative phenotype, knowledge of which may improve treatment strategies for this disastrous tumor type. The invasive phenotype is specific for glioma: most other brain tumor types, both primary and metastatic, grow as delineated lesions. Differences between the genetic make-up of glioma and that of other tumor types may therefore help to unravel molecular pathways, involved in diffuse infiltrative growth. One such difference concerns mutations in the NADP⁺-dependent isocitrate dehydrogenase (IDH1 and IDH2) genes, which occur in > 80% of cases of low grade glioma and secondary glioblastoma. In this review we present a novel hypothesis which links IDH1 and IDH2 mutations to glutamate metabolism, possibly explaining the specific biological behavior of diffuse glioma.     

Topology characterization by MALDI-ToF-MS of enzymatically synthesized poly(lactide-co-glycolide)

Lipase catalyzed copolymerization of the monomers lactide and glycolide by Pseudomonas cepacia employing a molar ratio of 80L/20G has been studied. The copolymers were characterized by MALDI-ToF-MS, DSC, SEC and NMR. MALDI-ToF-MS has successfully been used not only to determine end groups and chemical composition but even the microstructure of the copolymers. We demonstrated that for this lipase catalyzed copolymerization, the main product of the reaction at 100 degrees C was linear homopolymer of lactide while at 130 degrees C the main product was cyclic random copolymer.     

Hyperpolarized 129Xe MR Imaging of Alveolar Gas Uptake in Humans

Background

One of the central physiological functions of the lungs is to transfer inhaled gases from the alveoli to pulmonary capillary blood. However, current measures of alveolar gas uptake provide only global information and thus lack the sensitivity and specificity needed to account for regional variations in gas exchange.

Methods and Principal Findings

Here we exploit the solubility, high magnetic resonance (MR) signal intensity, and large chemical shift of hyperpolarized (HP) ¹²⁹Xe to probe the regional uptake of alveolar gases by directly imaging HP ¹²⁹Xe dissolved in the gas exchange tissues and pulmonary capillary blood of human subjects. The resulting single breath-hold, three-dimensional MR images are optimized using millisecond repetition times and high flip angle radio-frequency pulses, because the dissolved HP ¹²⁹Xe magnetization is rapidly replenished by diffusive exchange with alveolar ¹²⁹Xe. The dissolved HP ¹²⁹Xe MR images display significant, directional heterogeneity, with increased signal intensity observed from the gravity-dependent portions of the lungs.

Conclusions

The features observed in dissolved-phase ¹²⁹Xe MR images are consistent with gravity-dependent lung deformation, which produces increased ventilation, reduced alveolar size (i.e., higher surface-to-volume ratios), higher tissue densities, and increased perfusion in the dependent portions of the lungs. Thus, these results suggest that dissolved HP ¹²⁹Xe imaging reports on pulmonary function at a fundamental level.