Modeling inflammation and oxidative stress in gastrointestinal disease development using novel organotypic culture systems.

Gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), graft-versus-host disease (GVHD), and inflammatory bowel diseases such as ulcerative colitis and Crohn's disease are common human gastrointestinal diseases that share inflammation as a key driver for their development. A general outcome resulting from these chronic inflammatory conditions is increased oxidative stress. Oxidative stress is caused by the generation of reactive oxygen and nitrogen species that are part of the normal inflammatory response, but are also capable of damaging cellular DNA, protein, and organelles. Damage to DNA can include DNA strand breaks, point mutations due to DNA adducts, as well as alterations in methylation patterns leading to activation of oncogenes or inactivation of tumor suppressors. There are a number of significant long-term consequences associated with chronic oxidative stress, most notably cancer. Infiltrating immune cells and stromal components of tissue including fibroblasts contribute to dynamic changes occurring in tissue related to disease development. Immune cells can potentiate oxidative stress, and fibroblasts have the capacity to contribute to advanced growth and proliferation of the epithelium and any resultant cancers. Disease models for GERD, BE, GVHD, and ulcerative colitis based on three-dimensional human cell and tissue culture systems that recapitulate in vivo growth and differentiation in inflammatory-associated microphysiological environments would enhance our understanding of disease progression and improve our ability to test for disease-prevention strategies. The development of physiologically relevant, human cell-based culture systems is therefore a major focus of our research. These novel models will be of enormous value, allowing us to test hypotheses and advance our understanding of these disorders, and will have a translational impact allowing us to more rapidly develop therapeutic and chemopreventive agents. In summary, this work to develop advanced human cell-based models of inflammatory conditions will greatly improve our ability to study, prevent, and treat GERD, BE, GVHD, and inflammatory bowel disease. The work will also foster the development of novel therapeutic and preventive strategies that will improve patient care for these important clinical conditions

Retention of mouth-to-mouth, mouth-to-mask and mouth-to-face shield ventilation

Background: Retention of mouth-to-mouth, mouth-to-mask and mouth-to-face shield ventilation techniques is poorly understood.Methods: A prospective randomised clinical trial was undertaken in January 2004 in 70 candidates randomly assigned to training in mouth-to-mouth, mouth-to-mask or mouth-to-face shield ventilation. Each candidate was trained for 10 min, after which tidal volume, respiratory rate, minute volume, peak airway pressure and the presence or absence of stomach inflation were measured. 58 subjects were reassessed 1 year later and study parameters were recorded again. Data were analysed with ANOVA, \textgreekq2 and McNemar tests.Results: Tidal volume, minute volume, peak airway pressure, ventilation rate and stomach inflation rate increased significantly at reassessment with all ventilation techniques compared with the initial assessment. However, at reassessment, mean (SD) tidal volume (960 (446) vs 1008 (366) vs 1402 (302) ml; p<0.05), minute volume (12 (5) vs 13 (7) vs 18 (3) l/min; p<0.05), peak airway pressure (14 (8) vs 17 (13) vs 25 (8) cm H2O; p<0.05) and stomach inflation rate (63% vs 58% vs 100%; p<0.05) were significantly lower with mouth-to-mask and mouth-to-face shield ventilation than with mouth-to-mouth ventilation. The ventilation rate at reassessment did not differ significantly between the ventilation techniques.Conclusions: One year after a single episode of ventilation training, lay persons tended to hyperventilate; however, the degree of hyperventilation and resulting stomach inflation were lower when a mouth-to-mask or a face shield device was employed. Regular training is therefore required to retain ventilation skills; retention of skills may be better with ventilation devices

More on Symmetries in Heavy Quark Effective Theory

We present a general classification of all normal and ``chiral" symmetries of heavy quark effective theories. Some peculiarities and conondrums associated with the ``chiral" symmetries are discussed.Comment: 15 pages, preprint UR-1320, ER40685-77

Lymphoepithelial Cyst of the Pancreas: Serum Markers do not Help

We report a case of lymphoepithelial cyst of the pancreas with non-specific elevation of CA 19.9 and CEA. Pre-operative diagnosis by conventional means proved elusive, and only surgical resection and histopathology revealed the diagnosis. The origin and diagnosis are discussed by literature review

ρ\rho Polarization and `Model Independent' Extraction of ∣Vub∣/∣Vcd∣|V_{ub}|/|V_{cd}| from D→ρℓνD\to\rho\ell\nu and B→ρℓνB\to\rho\ell\nu

We briefly discuss the predictions of the heavy quark effective theory for the semileptonic decays of a heavy pseudoscalar to a light one, or to a light vector meson. We point out that measurement of combinations of differential helicity decay rates at Cleo-c and the $B$ factories can provide a model independent means of extracting the ratio $|V_{ub}|/|V_{cd}|$. We briefly discuss the corrections to this prediction.Comment: 8 pages, LaTeX, 1 figur

Radiative Leptonic Decays of Heavy Mesons

We compute the photon spectrum and the rate for the decays $B(D)\to l\nu_l\gamma$ These photonic modes constitute a potentially large background for the purely leptonic decays which are used to extract the heavy meson decay constants. While the rate for D\to l\n\g is small, the radiative decay in the $B$ meson case could be of comparable magnitude or even larger than B\to\m\n. This would affect the determination of $f_B$ if the $\tau$ channel cannot be identified. We obtain theoretical estimates for the photonic rates and disscuss their possible experimental implications.Comment: 12 pages, RevTex, 3 uuencoded figures include

A relativistic chiral quark model for pseudoscalar emission from heavy mesons

The amplitudes for one-pion mediated transitions between heavy meson excited states are obtained in the framework of the relativistic chiral quark model. The effective coupling constants to pions and the decay widths of excited heavy mesons with l<=2 for non-radially excited, and the l=0 radially excited mesons are presented for both charmed and beauty mesons. We also discuss the allowed decays of strange excited heavy mesons by emission of a K-meson.Comment: 20 pages, revte

Small denominators, frequency operators, and Lie transforms for nearly integrable quantum spin systems

Based on the previously proposed notions of action operators and of quantum integrability, frequency operators are introduced in a fully quantum-mechanical setting. They are conceptually useful because another formulation can be given to unitary perturbation theory. When worked out for quantum spin systems, this variant is found to be formally equivalent to canonical perturbation theory applied to nearly integrable systems consisting of classical spins. In particular, it becomes possible to locate the quantum-mechanical operator-valued equivalent of the frequency denominators that may cause divergence of the classical perturbation series. The results that are established here link the concept of quantum-mechanical integrability to a technical question, namely, the behavior of specific perturbation series

Model-Independent Semileptonic Form Factors Using Dispersion Relations

We present a method for parametrizing heavy meson semileptonic form factors using dispersion relations, and from it produce a two-parameter description of the B -> B elastic form factor. We use heavy quark symmetry to relate this function to B -> D* l nu form factors, and extract |V_cb|=0.0355^{+0.0029}_{-0.0025} from experimental data with a least squares fit. Our method eliminates model-dependent uncertainties inherent in choosing a parametrization for the extrapolation of the differential decay rate to threshold.Comment: uses lanlmac(harvmac) and epsf, 12 pages, 1 eps figure included (Talk by BG at the 6-th International Symposium on Heavy Flavour Physics, Pisa, Italy, 6--10 June, 1995