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Background 5-aminosalicylic acid (5-ASA) is widely used as a first-line treatment for ulcerative colitis (UC), but intolerance sometimes occurs. 5-ASA-intolerance was considered a risk factor for colectomy in UC patients, but no reports have examined which treatment is suitable to avoid colectomy in 5-ASA-intolerant UC patients. This is the first report describing a treatment strategy for 5-ASA-intolerant UC. The aims of this study were to determine the optimal therapeutic strategy in 5-ASA-intolerant UC patients. Methods This retrospective cohort study involved patients who were newly diagnosed as having UC after January 2010 and who received oral 5-ASA agents. Patients were considered 5-ASA-intolerant when they fulfilled two or more of the following conditions: (1) paradoxical aggravation of colitis on introducing oral 5-ASA agents or allergic reactions to the agents; (2) obvious improvement of abdominal symptoms after discontinuation of 5-ASA agents; (3) positive drug-induced lymphocyte stimulation test (DLST) for at least two formulations of 5-ASA; (4) adverse events following re-challenge with 5-ASA agents; and (5) severe adverse events owing to 5-ASA agents. Results Of 950 UC patients with a history of 5-ASA administration, 213 (22.4%) were considered 5-ASA-intolerant. Five-year colectomy-free survival was significantly lower in 5-ASA-intolerant patients compared with 5-ASA-tolerant patients (73% vs. 84%, respectively). From the multivariate Cox proportional hazards model analysis in the 5-ASA-intolerant patient cohort, thiopurine use was shown to contribute to avoidance of colectomy in 5-ASA-intolerant patients (hazard ratio = 0.25; 95% confidence interval, 0.13–0.47; P < 0.001); however, 5-ASA-intolerant patients were also likely to be thiopurine-intolerant compared with 5-ASA-tolerant patients (27% vs. 15%, respectively; P = 0.04). Calcineurin inhibitor use was associated with an increased risk of colectomy (hazard ratio = 4.80; 95% confidence interval, 2.24–10.3; P < 0.001), while treatment with systemic corticosteroids and biologics did not affect the colectomy rate (hazard ratio = 1.07; 95% confidence interval, 0.60–1.91; P = 0.81). Conclusion Treatment with thiopurines demonstrated the potential to improve the prognosis in 5-ASA-intolerant patients. However, it should be noted that thiopurine intolerance was more frequent in 5-ASA-intolerant patients. Compared to biologics, calcineurin inhibitors may not contribute to avoidance of colectomy, and biologics may be preferred for intractable patients with 5-ASA intolerance. This is the first report describing a treatment strategy for 5-ASA-intolerant UC, and we believe it will have many implications in clinical practice.

Background Biologics are widely used for paediatric Crohn's disease (CD) and are highly effective; however, primary inefficacy and the emergence of secondary inefficacy during long-term use remain challenges. Although it is desirable for biologics used in paediatric patients to be safe and usable long-term, there are few detailed reports on the comparison of persistence rates of biologics in paediatric patients. Methods This was a multicentre prospective cohort study using a web-based registry system in Japan that was performed between October 2012 and March 2020. New paediatric inflammatory bowel disease patients diagnosed at less than 18 years of age were enrolled from 23 Japanese hospitals. The persistence rates of the first biologics (Infliximab: IFX and Adalimumab: ADA), and the second biologics (IFX, ADA, and Ustekinumab: UST) were analysed. Patients with unknown outcomes were excluded. Results We enrolled 185 patients with CD as the final diagnosis, and 109 (59%) received biologics during the observation period. As the first biologic, IFX was used in 52 (45%) patients, ADA in 52 (45%), UST and Vedolizumab (VED) in one, respectively, and the biologic in one patient was unidentified. The 1-, 3- and 5-year persistence rates of IFX and ADA as the first biologic were 90%, 70% and 61% for IFX, and 80%, 71% and 49% for ADA, respectively (Fig.1), with no statistically significant difference (P=0.31). There was also no statistically significant difference after propensity score matching (P=0.27). Multivariate analysis showed that Paris classification L4a and b were independent risk factors for lower retention of biologics in IFX and ADA. Of the 104 patients whose first biologic was IFX or ADA, 31 patients were treated with a second biologic (IFX: 7, ADA: 6, UST: 15, VED: 2 and unknown: 1). The 1- and 3-year persistence rates of the second biologic were 86% and 51% for IFX; 80% and 80% for ADA and 100% and 100% for UST, respectively (Fig.2). Conclusion The persistence rates of IFX and ADA as first biologics were similar in paediatric patients with CD, and the persistence rates of UST tended to be higher than IFX or ADA as second biologics, although the differences were not statistically significant.

Background Intestinal Behçet's disease (BD) is a relapsing-remitting disease typically associated with punched-out ulcers in the ileocecal region. Optimal monitoring of disease activity is necessary; however, ileocolonoscopy cannot be performed on a regular basis as it is invasive, resource-intensive and causes considerable patient discomfort. Furthermore, there are risks of intestinal bleeding and perforation caused by pretreatment laxatives and air insufflation during the examination. Hence, other follow-up examinations are required. Intestinal ultrasonography (IUS) is a minimally invasive imaging method, but there are no previous reports of comparisons between IUS and endoscopy for intestinal BD. This study aimed to evaluate the usefulness of IUS in assessing the activity of ileocecal ulcers in intestinal BD. Methods This retrospective single-centre study included patients with intestinal BD who underwent colonoscopy and IUS within 2 weeks, from 2007 to 2020. Correlations between the corresponding endoscopic activity using the Sakita–Miwa classification and six IUS variables (bowel wall thickness [BWT], vascularity, bowel wall stratification, intramural and extramural abscesses, fistulas and mesenteric lymphadenopathy) were assessed and used to select the variables that should be included in the new simple score. IUS findings were also compared with biomarker (C-reactive protein [CRP]) concentrations and clinical severity indices (Crohn’s disease activity index and disease activity index for intestinal BD [DAIBD]). Results Seventy-nine IUS examinations from 53 patients were included. Univariate analysis revealed that CRP and DAIBD and the IUS findings BWT, vascularity and bowel wall stratification and intramural and extramural abscesses differed significantly according to endoscopic ulcer activity. Multivariate analysis using a logistic regression model revealed that only BWT and vascularity were statistically different; therefore, a new simple score ([2*BWT] + [5*vascularity]) was constructed. Receiver operating characteristic curve analysis revealed an area under the curve of 0.91 for detecting endoscopic activity, which was superior to those of CRP (0.80; P=0.069), Crohn’s disease activity index (0.69; P=0.002) and DAIBD (0.67; P Conclusion A new simple ultrasound activity index for intestinal BD comprising BWT and vascularity was constructed and correlated well with endoscopic disease activity. This is the first report describing the usefulness of IUS for intestinal BD, and we believe the findings will have many implications in clinical practice.

Background Current consensus statements recommend at least 3–6 months of preconception steroid-free remission for women with inflammatory bowel disease, as determined by experts. However, little data is available on the appropriate preconception remission period in women with ulcerative colitis (UC). We explored the effect of the preconception steroid-free remission period on disease activity during pregnancy and birth outcomes in women with UC. Methods Data were obtained from a retrospective chart review of 141 consecutive pregnant women with UC at our inflammatory bowel disease centre and a related clinic from 2000–2020. Women who were diagnosed with UC more than 6 months before conception and who were judged to have been accurately assessed for disease activity during the 6-month preconception period and at each trimester during pregnancy were included. We categorized the women into four subgroups according to their preconception steroid-free remission periods (≥6 months, 3–6 months, Results The rate of active disease during pregnancy was 63% in the ≥6 months preconception steroid-free remission group, 50% in the 3–6 months preconception steroid-free remission group, 71% in the 0.05). Conclusion The largest risk factor for disease activity during pregnancy appears to be active disease at conception. A shorter preconception steroid-free remission period than the recommended 3–6 months might reduce the risk of disease activity during pregnancy.

Background Serrated polyps are recognized as precursors of colorectal cancer in general population and have recently been reported in patients with ulcerative colitis (UC). However, their prevalence and detailed characteristics remain unclear. Methods The prevalence and clinicopathological and biological characteristics of serrated polyps in patients with UC were retrospectively examined in a single tertiary inflammatory bowel disease centre in Japan from 2000 to 2020. Results In total, 252 neoplasms, including 36 serrated polyps (26 in colitis-affected segments, 10 in colitis-unaffected segments), were identified in 187 patients with UC. The proportion of serrated polyps was significantly higher from 2010 to 2020 (35/213, 17%) than from 2000 to 2009 (1/39, 3%; p = 0.023). Serrated polyps in colitis-affected segments were common in patients with extensive colitis (88%), a history of persistent active colitis (58%), and a long duration of UC (12.1 years). Serrated polyps in colitis-affected segments were more common in men (88%). Of 26 serrated polyps in colitis-affected segments, 15, 6, and 5 were categorized as sessile serrated lesion (SSL)-like dysplasia, traditional serrated adenoma (TSA)-like dysplasia, and serrated dysplasia not otherwise specified (SD NOS), respectively. SSL-like dysplasia was common in the proximal colon (67%) and with BRAF mutation (62%), whereas TSA-like dysplasia and SD NOS were common in the distal colon (100% and 80%) and with KRAS mutations (100% and 75%). CpG island hypermethylation phenotype-positive status was observed in 60% cases of TSA-like dysplasia but in only 25% cases of SSL-like dysplasia and SD NOS. Conclusion Serrated polyps have recently been increasing in patients with UC. Serrated polyps in colitis-affected segments were common in men with extensive and longstanding colitis, suggesting that chronic inflammation is involved in the development of serrated polyps in patients with UC.

Introduction/Background Patients with Parkinson's disease (PD) suffer from gait disturbance that, in some patients, can be improved by rhythmic stimulation. This effect is useful for their rehabilitation, but its physiological mechanism is not yet well understood. The purpose of this study is to investigate brain activation patterns with functional magnetic resonance imaging (fMRI) in patients with PD while they are imaging gait with and without rhythmic stimulation. Material and method The participants were 27 right-handed patients with PD (mean age: 76.3 ± 6.6, 11 male), whose Yahr stages ranged from 2 to 3. They could walk independently, had no cognitive impairment, and could walk more smoothly with rhythmic stimulation than without it. As a control group, we examined 7 healthy 25 right-handed volunteers (mean age: 72.0 ± 5.3, 13 males). The participants were asked to image gait with rhythmic stimulation (beep on 100 beats per minute) or with white noise during the fMRI imaging. Results In patients with PD, with rthmic sound, the activation pattern was limited to supplementary motor area (SMA) and precentral lobule, while with white noise, the activation pattern was more widespread, including precuneus as well as SMA and precentral lobule (P Conclusion Both SMA and precentral lobule were activated while other regions including precuneus were less activated with rhythmic stimulation in patients with PD. This result may suggest that rhythmic stimulation can suppress the overactivation of precuneus to improve the attention and to correct the motor programs for the gait function in these patients. In this study, we could suggest the mechanism of the immediate effect of gait improvement with rhythmic stimulation.

In 2004, we searched for very high energy (VHE) gamma-ray emission from the Galactic Plane using the CANGAROO-III stereoscopic observation system. Two different longitude regions (l = −19°.5 and l = +13°.0) on the Galactic Plane were observed during July and August 2004. We analyzed events that triggered three telescopes aiming to measure the diffuse emission component. No significant signal associated with the Galactic Plane was found from either of the regions. Assuming that the gamma-ray spectrum is described by a single power-law for energies ranging between a few GeV and TeV, lower limits of the power-law spectral indices were found to be 2.2 for both of the regions with a 99.9% confidence level. This result is consistent with the other VHE measurements and constrains a hypothesis in which a very hard (∼2.0) cosmic ray electron spectrum was introduced to explain the EGRET GeV anomaly.

We observed the unidentified TeV gamma-ray source HESS J1804-216 with the CANGAROO-III atmospheric Cerenkov telescopes from May to July in 2006. We detected very high energy gamma rays above 600 GeV at the 10 sigma level in an effective exposure of 76 hr. We obtained a differential flux of (5.0+/-1.5_{stat}+/-1.6_{sys})\times 10^{-12}(E/1 TeV)^{-\alpha} cm^{-2}s^{-1}TeV^{-1} with a photon index \alpha of 2.69 +/- 0.30_{stat} +/- 0.34_{sys}, which is consistent with that of the H.E.S.S. observation in 2004. We also confirm the extended morphology of the source. By combining our result with multi-wavelength observations, we discuss the possible counterparts of HESS J1804-216 and the radiation mechanism based on leptonic and hadronic processes for a supernova remnant and a pulsar wind nebula., Comment: 11 pages, 12 figures, Accepted in ApJ

We have observed the supernova remnant MSH 15-52 (G320.4-1.2), which contains the gamma-ray pulsar PSR B1509-58, using the CANGAROO-III imaging atmospheric Cherenkov telescope array from April to June in 2006. We detected gamma rays above 810 GeV at the 7 sigma level during a total effective exposure of 48.4 hours. We obtained a differential gamma-ray flux at 2.35 TeV of (7.9+/-1.5_{stat}+/-1.7_{sys}) \times 10^{-13} cm^{-2}s^{-1}TeV^{-1} with a photon index of 2.21+/-0.39_{stat}+/-0.40_{sys}, which is compatible with that of the H.E.S.S. observation in 2004. The morphology shows extended emission compared to our Point Spread Function. We consider the plausible origin of the high energy emission based on a multi-wavelength spectral analysis and energetics arguments.

Optical images of SN 1987A show a triple ring structure. The inner (dust) ring has recently increased in brightness and in the number of hot spots suggesting that the supernova shock wave has collided with the dense pre-existing circumstellar medium, a scenario supported by radio and X-ray observations. Such a shocked environment is widely expected to result in the acceleration of charged particles, and the accompanying emission of very high energy gamma-rays. Here, we report the results of observations made in 2004 and 2006 which yield upper limits on the TeV gamma-ray flux, which are compared with a theoretical prediction. In addition, we set upper limits on the TeV flux for four high energy objects which are located within the same field of view of the observation: the super-bubble 30 Dor C, the Crab-like pulsar PSR B0540$-$69, the X-ray binary LMC X-1, and the supernova remnant N157B., Comment: 5 pages, 5 figures, Accepted for publication in ApJ

AC susceptibility measurements in mechanically alloyed (MA) Ni–20 at% Mn were made under hydrostatic pressures up to 7.5 GPa. The results were compared with a bulk alloy made by the conventional method of melting. The Curie temperature decreased with pressure at the rate of −6.9 and −8.0 K/GPa in MA and the bulk alloy, respectively. The transition temperature to the reentrant spin glass state increased at the rate of 1.2 and 1.7 K/GPa in MA and the bulk alloy, respectively. The results were explained by assuming a Gaussian distribution of concentration fluctuation.

著者人数: 51名, Accepted: 2004-12-10, 資料番号: SA1003414000

The performance of a single gamma-ray telescope is discussed based on the Imaging Atmospheric Cherenkov Technique (IACTech) at high altitudes. Observations at a high altitude are quite suitable for the IACTech because the density of Cherenkov light caused by gamma-rays is several-times larger than at sea level. To observe gamma-ray pulsars at high altitude, a gamma-ray camera, designated CheSS (Cherenkov light detecting System on Subaru) based on the IACTech, has been developed for the Subaru infrared-optical telescope at an altitude of 4200 m. Using CheSS, the Crab nebula/pulsar was observed for three days in December 2001. From a comparison between the simulated and observed shower events, it was found that the night-sky background (N.S.B.) and muon showers have significant effects on the detection rate below 80 GeV in spite of the small field of view (FOV) of CheSS (0.75°). The simulated spectrum, which includes muon shower events, is consistent with the observed spectrum. Based on this study, the performance of a camera with a larger FOV of 3.0° is discussed. Although the effects of muon showers and the N.S.B. become serious, the simulation results indicate that an 8.2 m Imaging Atmospheric Cherenkov Telescope (IACT) with a FOV of 3.0° at an altitude of 4200 m could detect 15 GeV energy gamma-rays.

著者人数: 51名, Accepted: 2004-03-24, 資料番号: SA1003408000

著者人数: 51名, 資料番号: SA1003983000

著者人数: 46名, Accepted: 2003-05-20, 資料番号: SA1003406000

Bacterial translocation across the gut wall may be associated with insult to the latter. In this situation, intestinal flora can enter the blood stream and lymph nodes and be transported to other organs. Glutamine is a nonessential amino acid not presently included in total parenteral nutrition (TPN) preparations. The use of glutamine-enriched TPN in the rat has resulted in a significant reduction in bacterial translocation. This study attempted to evaluate the role of glutamine in preventing bacterial translocation following hemorrhagic shock in a rat model. Forty Sprague-Dawley rats were equally divided into two groups. The controls were given TPN solution, while the treated group had glutamine instead of the standard alanine present in TPN. Hemorrhagic shock was induced in both groups and blood cultures were performed. Glutamine-treated rats did not show a significant difference in survival suggesting that it is of no particular value in severe hemorrhagic shock in rats.

Because accretion and merger shocks in clusters of galaxies may accelerate particles to high energies, clusters are candidate sites for the origin of ultra-high-energy (UHE) cosmic-rays. A prediction was presented for gamma-ray emission from a cluster of galaxies at a detectable level with the current generation of imaging atmospheric Cherenkov telescopes. The gamma-ray emission was produced via inverse Compton upscattering of cosmic microwave background (CMB) photons by electron-positron pairs generated by collisions of UHE cosmic rays in the cluster. We observed two clusters of galaxies, Abell 3667 and Abell 4038, searching for very-high-energy gamma-ray emission with the CANGAROO-III atmospheric Cherenkov telescope system in 2006. The analysis showed no significant excess around these clusters, yielding upper limits on the gamma-ray emission. From a comparison of the upper limit for the north-west radio relic region of Abell 3667 with a model prediction, we derive a lower limit for the magnetic field of the region of ~0.1 micro G. This shows the potential of gamma-ray observations in studies of the cluster environment. We also discuss the flux upper limit from cluster center regions using a model of gamma-ray emission from neutral pions produced in hadronic collisions of cosmic-ray protons with the intra-cluster medium (ICM). The derived upper limit of the cosmic-ray energy density within this framework is an order of magnitude higher than that of our Galaxy., 7 pages, 6 figures, Accepted in ApJ

Kepler's supernova, discovered in October 1604, produced a remnant that has been well studied observationally in the radio, infrared, optical, and X-ray bands, and theoretically. Some models have predicted a TeV gamma-ray flux that is detectable with current Imaging Cherenkov Atmospheric Telescopes. We report on observations carried out in 2005 April with the CANGAROO-III telescope. No statistically significant excess was observed, and limitations on the allowed parameter range in the model are discussed., 6 pages 6 figures, to appear in ApJ, August 20, 2008, v683n2

We have used the CANGAROO-III imaging atmospheric Cherenkov telescopes to observe the high-frequency-peaked BL Lacertae (HBL) object PKS 2155-304 between 2006 July 28 (MJD 53944) and August 2, triggered by the H.E.S.S. report that the source was in a high state of TeV gamma-ray emission. A signal was detected at the 4.8 sigma level in an effective live time of 25.1 hours during the outburst period. The flux of Very High Energy gammarays from the CANGAROO-III observations shows the variability on the time scale of less than a few hours. The averaged integral flux above 660 GeV is (1.6 +/- 0.3_stat +/- 0.5_syst) x 10^-11 cm^-2 sec^-1 which corresponds to ~45% of the flux observed from the Crab nebula. Follow-up observations between August 17 (MJD 53964) and 25 indicate the source activity had decreased., 24 pages, 7 figures, to be published in ApJ

We have observed the giant radio galaxy Centaurus A and the globular cluster $\omega$ Centauri in the TeV energy region using the CANGAROO-III stereoscopic system. The system has been in operation since 2004 withan array of four Imaging Atmospheric Cherenkov Telescopes (IACT) with $\sim$100-m spacings. The observations were carried out in March and April 2004. In total, approximately 10 hours data were obtained for each target.No statistically significant gamma-ray signal has been found above 420 GeV over a wide angular region (a one-degree radius from thepointing center) and we derive flux upper limits using all of the field of view.Implications for the total energy of cosmic rays and the density of the cold dark matter are considered., Comment: 7 pages, 6 figures, to appear in ApJ, emulateapj.cls

Sub-TeV gamma-ray emission from the North-West rim of the supernova remnant RX J0852.0$-$4622 was detected with the CANGAROO-II telescope and recently confirmed by the H.E.S.S. group. In addition, the H.E.S.S. data revealed a very wide (up to two degrees in diameter), shell-like profile of the gamma-ray emission. We have carried out CANGAROO-III observations in January and February 2005 with three telescopes and show here the results of three-fold coincidence data. We confirm the H.E.S.S. results about the morphology and the energy spectrum, and find the energy spectrum in the NW-rim is consistent with that of the whole remnant., 9 pages, 13 figures, to appear in ApJ

We made stereoscopic observations of the Vela Pulsar region with two of the 10 m diameter CANGAROO-III imaging atmospheric Cherenkov telescopes in January and February, 2004, in a search for sub-TeV gamma-rays from the pulsar and surrounding regions. We describe the observations, provide a detailed account of the calibration methods, and introduce the improved and bias-free analysis techniques employed for CANGAROO-III data. No evidence of gamma-ray emission is found from either the pulsar position or the previously reported position offset by 0.13 degree, and the resulting upper limits are a factor of five less than the previously reported flux from observations with the CANGAROO-I 3.8 m telescope. Following the recent report by the H.E.S.S. group of TeV gamma-ray emission from the Pulsar Wind Nebula, which is $\sim$0.5 degree south of the pulsar position, we examined this region and found supporting evidence for emission extended over $\sim$0.6 degree., 13 pages, 26 figures, emulateapj.cls, to appear in ApJ

著者人数: 46名, Accepted: 2004-02-16, 資料番号: SA1003381000

We developed the gamma-ray camera for SUBARU infrared-optical telescope, named CheSS (Cherenkov light detecting System on Subaru). The CheSS was designed based on Imaging Atmospheric Cherenkov Technique (IACT) which has been established by detections of high energy gamma-ray sources in the last decade. According to our Monte Carlo simulation, the energy thresholds of the CheSS for the Crab are 30 GeV at zenith angle of 10 degrees, and the expected sensitivity for the unpulsed component can reach ~10σ level and more for pulsed one during 10 hours on-source pointing.

著者人数: 45名, Accepted: 2003-02-14, 資料番号: SA1003347000

We report the TeV gamma-ray observations of the nearby normal spiral galaxy NGC 253. At a distance of $\sim$2.5 Mpc, NGC 253 is one of the nearest starburst galaxies. This relative closeness, coupled with the high star formation rate in the galaxy, make it a good candidate TeV gamma-ray source. Observations were carried out in 2000 and 2001 with the CANGAROO-II 10 m imaging atmospheric Cerenkov telescope. TeV gamma-ray emission is detected at the $\sim 11\sigma$ level with a flux of $(7.8 \pm 2.5)\times 10^{-12} {\rm cm}^{-2} {\rm sec}^{-1}$ at energies $>$0.5 TeV. The data indicate that the emission region is broader than the point spread function of our telescope., Comment: 4 pages, double colomn, 3 figures, aa.cls

著者人数: 47名, Accepted: 2002-12-02, 資料番号: SA1003998000

To develop an isolated rabbit lung model in which oxygen free radical activity could be measured and to examine the effects on the model of oxygen free radical scavengers.Prospective, randomized study.A clinical and basic research facility attached to a teaching hospital.Twenty-five New Zealand white rabbits weighing 3.5 to 4.5 kg.The mechanism of lung injury by oleic acid or by phorbol myristate acetate (20 ng/mL) plus polymorphonuclear neutrophils (PMA-PMN) in an ex vivo rabbit shock lung model may be the production of oxygen free radicals. Using a standard heart-lung preparation from these rabbits, baseline mean pulmonary artery pressure was maintained at 15 mm Hg and the mean airway pressure at 10 mm Hg. Experimental perfusates were infused over 30 minutes, followed by Krebs-Henseleit solution, pH 7.4. Dimethyl pyrroline oxide trapped oxygen free radicals, levels of which were measured by electron paramagnetic resonance spectroscopy. Lung injury was assessed by light and scanning electron microscopy and by lung weight.A 5-fold increase in pulmonary artery pressure (P.001) and a nearly 3-fold increase in mean airway pressure (P.001) were observed in both the oleic acid and PMA-PMN models. Superoxide dismutase (20,000 U/kg), but not retinol palmitate (2000 U), prevented lung injury, the increases in pulmonary artery pressure and mean airway pressure, and the increase in oxygen free radicals in the PMA-PMN model. There were no increases in oxygen free radicals in the control, oleic acid, or PMA-PMN/superoxide dismutase groups (n = 5 in each group). Maximum mean +/- SD increases in oxygen free radicals were 112 +/- 22 nmol/L in the PMA-PMN group (P.003, n = 5) and 108 +/- nmol/L in the PMA-PMN/retinol group (P.003, n = 5).The mechanism of lung injury in the PMA-PMN model is an increase in oxygen free radicals, because superoxide dismutase prevents both the rise in oxygen free radicals and lung injury. Administration of retinol does not prevent lung injury. Oleic acid produces injury not by an increase in oxygen free radicals but rather by another, unknown mechanism.