Effect of celecoxib on cyclooxygenase-2 expression and possible variants in a patient with Barrett's esophagus.

Cyclooxygenase-2 (COX-2) expression is increased in metaplastic and dysplastic Barrett's esophageal epithelium and it is thought that selective COX-2 inhibitors could offer hope as chemoprevention therapy. The aim of the study was to investigate the in vivo effect of celecoxib on COX-2 expression in patients with Barrett's esophagus and no recent history of non-steroidal anti-inflammatory drug use. Endoscopic mucosal biopsy specimens were collected at baseline and after 28 days of therapy in a patient treated with celecoxib 200 mg twice daily. Samples were analyzed for COX-2 expression by immunoblot analysis with chemiluminescence detection. COX-2 expression was found to decline 20% and 44% at two different biopsy sites compared to the baseline sample. Longer exposures revealed a number of previously unidentified proteins above and below the 67 kDa COX-2 protein including 38 kDa and 45 kDa proteins which were present only at study completion consistent with up-regulation after celecoxib therapy. Further investigations of the 38 kDa and 45 kDa proteins were undertaken using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) with immunoblot and MALDI-TOF (matrix assisted laser desorption ionization - time of flight) analysis but no matches were found and results were inconclusive. Unmatched masses from MALDI-TOF peptide mass fingerprinting were compared with human COX-2 (67 kDa) and COX-2b (39 kDa) using unspecific cleavage. Peptide sequence homology with COX-2 and COX-2b was found for a length of 19 amino acids. Based on immunodetection, molecular weight and equivical MALDI-TOF results, one of these up-regulated proteins may be COX-2b.

A High-Resolution Microwave Study of the Conformations of Butan-2-ol in a Supersonic Expansion.

The microwave Fourier transform spectrum of the chiral, secondary alcohol butan-2-ol has been recorded in the range 6-18 GHz. The spectrum is relatively dense, due to the large number of species formed in the supersonic expansion used. Three conformational isomers of the butan-2-ol molecule have been identified and their spectra assigned using a semirigid, asymmetric-rotor model. They correspond to the three configurations that the central C-C bond can adopt. The basis of our assignment is a series of ab initio calculations, which have been performed using the GAUSSIAN 94 package, good agreement being observed between theoretical and experimental values of the rotational constants. First-order centrifugal distortion coefficients have also been extracted. It has proven possible, by examination of the relative strengths of a-, b-, and c-type transitions, to infer some further information about the position of the hydroxyl hydrogen atom within each conformer. Copyright 2001 Academic Press.

The Dynamics of N(2)-O(3) and N(2)-SO(2) Probed by Microwave Spectroscopy.

The microwave spectra of N(2)-O(3) and N(2)-SO(2) have been recorded in the 6-18 GHz range using a pulsed-nozzle, Fourier transform microwave spectrometer. C-type transitions have been observed for both complexes which are slightly shifted by internal tunneling motions of the O(3) or SO(2) moieties. In addition, unshifted a-type transitions have been observed for N(2)-O(3). The nuclear hyperfine pattern is typical of equivalent nitrogen nuclei. Two sets of rotational and hyperfine constants are required to fit the symmetric and antisymmetric nuclear spin states, indicating that the equivalence arises from tunneling rotation of the nitrogen molecule. Internal tunneling motions along three tunneling pathways have been identified, although no information on the N(2) tunneling frequency is available from the spectra. From the N(2)-O(3) data the tunneling frequencies cannot be decorrelated from the rotational parameters; however, the O(3) tunneling frequency upper limit is estimated to be 2.0 MHz and the frequency of the concerted tunneling motion of both moieties is estimated to be about 8.9 MHz. For N(2)-SO(2), the SO(2) tunneling frequency is 11.5 kHz and the concerted frequency 173.9 kHz. Both complexes are roughly T shaped with the N(2) axis approximately perpendicular to the O(3) or SO(2) plane. In the equilibrium structures of both complexes, the a-c inertial plane is a plane of symmetry. The centers of mass separations are estimated from the rotational parameters to be 3.582 Å for N(2)-O(3) and 3.875 Å for N(2)-SO(2). The angle between the symmetry axes of the O(3) or SO(2) and the line joining their centers of mass have been calculated as 130.84 degrees (or 49.16 degrees ) and 119.71 degrees (or 60.29 degrees ), respectively. From the quadrupole analysis, the average angle between the N(2) axis and the a-inertial axis is 32.12 degrees for N(2)-O(3) and 27.81 degrees for N(2)-SO(2). Model electrostatic and ab initio calculations confirm these structures. Differences between the experimental and calculated structural parameters highlight the role of tunneling dynamics in these complexes. Copyright 2000 Academic Press.

High-Resolution Infrared Diode Laser Spectroscopy of Ne-N2O, Kr-N2O, and Xe-N2O.

The rotationally resolved spectra of the van der Waals complexes Ne-N2O, Kr-N2O, and Xe-N2O have been investigated in the region of the nu3 N2O monomer vibrational band using a diode laser absorption spectrometer that is incorporated with a multipass cell and a pulsed jet. The spectra of these three complexes are completely analyzed using a normal asymmetric rotor Hamiltonian, and the effective molecular constants are accurately determined for both the ground and the excited vibrational states. These results show that, like Ar-N2O, the complexes have a T-shaped configuration in which the rare gas atom prefers to lie near to the oxygen side of N2O. The band origins of Rg-N2O (Rg = Ne, Ar, Kr, and Xe) are observed to shift by 0.36125, 0.15038, -0.10131, and -0.49066 cm-1 from that of the monomer, respectively. These band origin shifts are well explained by a simple model for the intermolecular potential. Copyright 1998 Academic Press.