We compared the effects of treatment with methylprednisolone or the 21-aminosteroids, U-74389 and U-74006F (Tirilizad mesylate), on hyperoxic lung injury and the associated expression of mRNA for ...several adhesion molecules in rats. Inhalation of > 95% oxygen for up to 72 hr in Sprague-Dawley rats produced a marked increase in lung weight and an accumulation of fluid in the thorax when compared with air-breathing controls. Hyperoxia also induced a marked neutrophil-rich influx of inflammatory cells into the bronchial lumen as measured by bronchoalveolar lavage. Neutrophil numbers in bronchoalveolar lavage fluid peaked after 60 hr of exposure to > 95% oxygen; this was associated with a marked upregulation of mRNA for the adhesion molecules P-selectin and E-selectin but not VCAM-1. mRNA for ICAM-1 was constitutively expressed at high levels in both air-breathing controls and in the lungs of rats exposed to high concentrations of oxygen. Pretreatment with the 21-aminosteroids reduced hyperoxic lung damage and improved survival times in animals exposed to > 95% oxygen. However, treatment with methylprednisolone significantly decreased survival times. Treatment with U-74389 did not significantly (p > 0.05) inhibit the BAL neutrophilia and did not significantly (p > 0.05) reduce hyperoxia-induced increases in mRNA expression for P-selectin and E-selectin. The inhibition of hyperoxic lung damage coupled with improved survival seen in treated animals suggests that 21-aminosteroids may provide valuable treatments for pulmonary disorders in which oxidant damage has been implicated.
Inhalation of aerosols of ovalbumin in sensitized guinea pigs produced a marked, bronchoalveolar eosinophilia 24 hr after challenge. The lung eosinophilia was not prevented by the cyclooxygenase ...inhibitors, indomethacin or PAF antagonists (WEB-2086 and L-652731) but was inhibited by methylprednisolone, the 5-LO inhibitor, U-66858 and a series of structural analogs of LTB4, U-75302, U-77692, U-75485 and U-78489. The effectiveness of LTB4 antagonists but not PAF antagonists in vivo was consistent with in vitro studies in which LTB4 was shown to be far more chemotactic than PAF for guinea pig eosinophils. LTB4 elicited maximal directional migration of guinea pig eosinophils at concentrations from 10(-7) M to 10(-9) M while PAF showed no effect over the same concentration range. The structural analogs of LTB4 were shown to inhibit LTB4 induced chemotaxis of guinea pig eosinophils and produced a dose-related inhibition of binding of LTB4 to guinea pig eosinophil membranes. To add further proof to the hypothesis that LTB4 contributed to the antigen-induced lung eosinophilia we attempted to measure LTB4 release into BAL fluid immediately after and at various time points up to 24 hr after antigen inhalation. However, using a sensitive radioimmunoassay (detection limit 10 pg/ml) very low levels of LTB4 (24.9-67.9 pg/ml) or its metabolite, 20-OH LTB4 (24.9-98.2 pg/ml) were detected in BAL fluid and these levels did not increase significantly following antigen provocation. Inhalation of LTB4 aerosols in unsensitized Brown-Norway rats or inhalation of aerosols of ovalbumin in sensitized Brown-Norway rats also produced a marked "late-phase" eosinophil-rich influx of inflammatory cells into the lungs. The lung eosinophilia in the rat was prevented by two structurally unrelated leukotriene B4 (LTB4) antagonists, U-75302 and Ly255283. These data implicate LTB4 as a mediator of allergen-induced bronchopulmonary eosinophilia. Leukotriene B4 antagonists may provide leads for the development of compounds which inhibit the chronic airway inflammation associated with asthma in man.
Signal-to-noise is a key ingredient in successful NMR experiments, a fact that has stimulated the development of dynamic nuclear polarization (DNP). In solid state magic angle spinning (MAS) NMR ...experiments, we have observed signal enhancements of 50-400 at 140 and 250 GHz operating frequencies, depending on a variety of experimental conditions. These experiments are possible because of the development of gyrotrons for generating the high frequency microwaves needed for DNP/NMR. We report progress in the development of tunable gyrotrons at 330 and 460 GHz for DNP/NMR spectroscopy. The successful recent demonstration of DNP/NMR enhancements using the 460 GHz gyrotron with a 700 MHz NMR spectrometer makes it the highest frequency DNP/NMR system currently in operation worldwide. A 527 GHz gyrotron is now under development for application in an 800 MHz NMR system. We present an overview of the systems and related THz technologies developed at MIT for DNP/NMR spectroscopy.
The Spectral and Photometric Imaging Receiver (SPIRE) on the European Space Agency's Herschel Space Observatory utilizes a pioneering design for its imaging spectrometer in the form of a Fourier ...Transform Spectrometer (FTS). The standard FTS data reduction and calibration schemes are aimed at objects with either a spatial extent much larger than the beam size or a source that can be approximated as a point source within the beam. However, when sources are of intermediate spatial extent, neither of these calibrations schemes is appropriate and both the spatial response of the instrument and the source's light profile must be taken into account and the coupling between them explicitly derived. To that end, we derive the necessary corrections using an observed spectrum of a fully extended source with the beam profile and the source's light profile taken into account. We apply the derived correction to several observations of planets and compare the corrected spectra with their spectral models to study the beam coupling efficiency of the instrument in the case of partially extended sources. We find that we can apply these correction factors for sources with angular sizes up to \theta_{D} ~ 17". We demonstrate how the angular size of an extended source can be estimated using the difference between the sub-spectra observed at the overlap bandwidth of the two frequency channels in the spectrometer, at 959<\nu<989 GHz. Using this technique on an observation of Saturn, we estimate a size of 17.2", which is 3% larger than its true size on the day of observation. Finally, we show the results of the correction applied on observations of a nearby galaxy, M82, and the compact core of a Galactic molecular cloud, Sgr B2.
We report microsecond pulse and CW results of a gyrotron operating near 460 GHz and 230 GHz at the second electron cyclotron harmonic and fundamental, respectively. Peak power levels of up to 70 W at ...the fundamental and 3 W at the second harmonic have been obtained in operation at up to 13 kV and 150 mA. The gyrotron has been operated continuously to achieve 3 W CW at the second harmonic. The gyrotron was also demonstrated as a wideband continuous frequency tunable oscillator by magnetically exciting fundamental higher order longitudinal modes. The gyrotron oscillator can be used for dynamic nuclear polarization (DNP) studies in conjunction with a 700 MHz (/sup 1/H), 16.5 T nuclear magnetic resonance (NMR) spectrometer.
Harmonic results of a 460 GHz gyrotron Hornstein, M.K.; Bajaj, V.S.; Griffin, R.G. ...
Fifth IEEE International Vacuum Electronics Conference (IEEE Cat. No.04EX786),
2004
Conference Proceeding
We report the first results of a 460 GHz second harmonic gyrotron. In microsecond pulse length operation at 13 kV and 110 mA, power levels in the order of 1 W have been observed at the TE/sub 2,6/ ...mode at 456.2 GHz and the TE/sub 0,6/ mode at 458.6 GHz. Modes at the fundamental, including the TE/sub 0,3/ at 238 GHz and the TE/sub 2,3/ at 233 GHz, have output powers up to 70 W. The TE/sub 5,2/ mode was observed to tune continuously in frequency from 246 GHz to 248 GHz. The gyrotron is being processed for CW operation. At present, more than 12 W have been obtained in CW operation in the TE/sub 2,3/ mode at 233 GHz.
The hemodynamic effects of a nifedipine infusion were investigated in eight dogs given fentanyl/pancuronium/nitrous oxide/oxygen anesthesia. Nifedipine (20 micrograms/kg) was given intravenously over ...two minutes immediately prior to each 30-minute infusion at 2 micrograms/kg/min, 4 micrograms/kg/min, and 6 micrograms/kg/min. The range of plasma nifedipine levels obtained was 52.1 to 113.7 ng/mL. The predominant hemodynamic effects were significant reductions in systemic vascular resistance (SVR) and mean aortic pressure (MAP), accompanied by a rise in cardiac index and heart rate (HR). Administration of calcium chloride (20 mg/kg) after the nifedipine infusion had no effect on SVR or MAP, but HR was significantly reduced. Serum epinephrine and norepinephrine levels increased after the infusion of nifedipine and suggested that fentanyl did not completely overcome the sympathetic response to the profound vasodilatation. The resulting tachycardia in combination with diastolic hypotension from nifedipine could have a detrimental effect on the myocardial oxygen balance.
The role of computed tomography in the evaluation of patients with intraabdominal hemorrhage in the absence of trauma history has received little attention. Representative cases are presented ...demonstrating how preangiographic, postangiographic, and combined computed tomography-angiography can aid in the diagnosis and localization of obscure causes of intraabdominal and gastrointestinal bleeding.
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