Sumie Shioya

The importance of polymorphonuclear leukocytes in lipopolysaccharide-induced superoxide anion production and lung injury: ex vivo observation in rat lungs.

Abstract. The purpose of this study is to determine if the polymorphonuclear leukocyte (PMN) is a major causative agent for lipopolysaccharide (LPS)-induced lung injury and responsible for the excess production of superoxide anion in the lung. We measured superoxide anion production from the lung and pulmonary capillary permeability in rats with and without PMN depletion. The superoxide anion production from the lung was measured using a purpose-built ex vivo chemiluminescence apparatus. Pulmonary capillary permeability was evaluated by the Evans blue dye extravasation method. PMN sequestration was determined by counting PMNs in histologic tissue specimens using microscopy. All rats received 3 mg/kg LPS intravenously. Examinations were undertaken at 2, 6, and 12 h after the LPS injection. The PMN-depleted group received cyclophosphamide 4 days before the LPS injection, which resulted in a PMN count of less than 200 cells/μl. In rats without PMN depletion, Evans blue dye extravasation increased significantly at 12 h after the LPS injection; PMN sequestration increased at 2, 6, and 12 h after the LPS injection; and superoxide anion production increased at 6 h and remained elevated at 12 h after the LPS injection. The increased permeability, PMN sequestration, and superoxide anion production were not seen in the PMN-depleted group. The contribution of the xanthine/xanthine oxidase system and alveolar macrophages to the observed superoxide anion production was negligible. We conclude that, in rats, the PMN is a major causative agent in LPS-induced lung injury and is responsible for the excess production of superoxide anion in the lung.

Effects of age on muscle energy metabolism and oxygenation in the forearm muscles

PURPOSE The effects of aging on muscle metabolism and oxygenation have not yet been elucidated. We evaluated the effects of aging on energy metabolism and oxygenation in sedentary healthy subjects by simultaneously measuring 31P-magnetic resonance spectroscopy (MRS) and near-infrared spectroscopy (NIRS). METHODS Nine young (28.1 +/- 5.0 yr) and nine older (61.4 +/- 4.6 yr) healthy subjects were studied. The 31P-MR spectrum was obtained every 15 s during and after hand gripping exercise. Intracellular pH (pHi) and PCr/(PCr+Pi) [PCr: phosphocreatine, Pi: inorganic phosphate] were calculated as an index of energy metabolism. The time constant of the PCr/(PCr+Pi) recovery (tau PCr) was calculated. With NIRS, we evaluated the recovery rates of oxygenated (RHbO2) and deoxygenated hemoglobin (RHb) during the initial 10 s of recovery. RESULTS The PCr/(PCr+Pi) and pHi at rest and at completion of the exercise and tau PCr did not differ between young and older subjects. However, RHbO2 and RHb were significantly slower in older subjects than in young subjects. CONCLUSIONS The results suggest that muscle energy metabolism in the forearm muscle was not affected by aging. The slower RHbO2 and RHb in older subjects suggested impaired O2 supply, which was probably due to impaired peripheral circulation caused by the process of aging.

Expression of Intercellular Adhesion Molecule-1 and Lymphocyte Function-Associated Antigen-1 on Alveolar Macrophages in the Acute Stage of Radiation-Induced Lung Injury in Rats

We investigated the expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) on alveolar macrophages and on lung tissue in the early stage of radiation-induced lung injury. Cells in the bronchoalveolar lavage and lung tissue were obtained from rats at various times between 1 and 8 weeks after 20 Gy of 60Co gamma irradiation of a hemithorax. These specimens were stained immunohistochemically with anti-ICAM-1 and anti-LFA-1alpha monoclonal antibodies. The expression of these factors was compared with that of a control group. The total number of alveolar macrophages in the bronchoalveolar lavage was significantly reduced from 1 to 3 weeks, and the number of neutrophils was significantly increased 2 and 3 weeks after irradiation. ICAM-1 and LFA-1 expression on alveolar macrophages was significantly increased starting 1 week after irradiation. The expression of ICAM-1 and LFA-1 on lung tissue was not elevated up to 8 weeks after irradiation. In conclusion, the increased expression of ICAM-1 and LFA-1 on alveolar macrophages as early as 1 week after irradiation suggests that adhesion molecules play a role in the development of radiation-induced lung injury.

Early damage to lung tissue after irradiation detected by the magnetic resonance T2 relaxation time.

We sought to determine whether nuclear magnetic resonance relaxation times of water in tissue would be useful to detect molecular damage in lung tissue within 2 weeks after irradiation. Tissue samples were obtained from the lungs of rats at various times between 1 and 14 days after exposure of a hemithorax to 20 Gy 60Co gamma irradiation. The spin-lattice relaxation time, T1, was measured by the inversion recovery method, and the spin-spin relaxation time, T2, was measured by both the Hahn spin-echo (Hahn T2) and the Carr-Purcell-Meiboom-Gill (CPMG T2) methods. The T2 of lung tissue could be divided into two components, T2 fast (T2f) and T2 slow (T2s), which reflected changes in the intracellular and extracellular water, respectively. The CPMG T2f increased significantly 3 days after irradiation (66.3 +/- 2.3 ms compared to 60.8 +/- 2.6 ms), and the CPMG T2s increased significantly 1 day after irradiation (155 +/- 11 ms compared to 138 +/- 7 ms), prior to the observation of abnormalities upon examination of the lung by light microscopy. The CPMG T2 values increased further up to 14 days after irradiation when significant increases were observed in values for T1, Hahn T2 and water content. Our results indicate that the molecular derangement in irradiated lung tissue was detected by the CPMG T2 measurement in the very early stage, and that MRI may be superior to conventional radiographs for detecting the early damage to lung tissue after irradiation.

MR appearance of pulmonary metastatic calcification

We report a case of metastatic pulmonary calcification that showed hyperintense signal on T1-weighted MRI. This uncommon MR appearance of calcification is similar to the MR characteristics of calcification in the brain due to abnormal calcium metabolism.

Gefitinib‐induced lung injury successfully treated with high‐dose corticosteroids

Abstract:  A 55‐year‐old man was treated with gefitinib for disseminated pleural lesions, 1 year after resection of the left lower lobe for non‐small cell lung cancer. After 6 weeks of continuous daily treatment with oral gefitinib, he developed dyspnoea on exertion and a non‐productive cough. CXR and CT revealed focal areas of ground‐glass opacity (GGO) in the right upper lobe. Despite gefitinib being discontinued, high‐resolution CT revealed extension of GGO and restructuring of lung parenchyma, suggesting acute interstitial pneumonia. Transbronchial biopsy revealed acute‐phase diffuse alveolar damage. After administration of methylprednisolone pulse therapy (1 g/day intravenously) for three consecutive days, the areas of GGO shrank on high‐resolution CT and symptoms resolved. Diffuse alveolar damage caused by gefitinib can be successfully treated in the early phase with high‐dose corticosteroids. Patients receiving gefitinib should be carefully examined for symptoms and undergo CT if their condition deteriorates.

Time domain reflectometry: measurement of free water in normal lung and pulmonary edema

The free water content of lung tissue was investigated by dielectric spectroscopy in normal lungs and in pulmonary edema induced by oleic acid in rats. The dielectric relaxation in a frequency range of 107 to 1010 Hz was measured with the time domain reflectometry method at 25°C. Three dielectric relaxation processes were analyzed for the lung tissue. A high-frequency process around 10 GHz was attributed to the orientation of free water molecules based on the relaxation time [log τh (in s) = -11.03]. The dielectric strength (Δε) of this high-frequency peak (Δεh) should reflect the amount of free water in the tissue. Because the measured Δεh depended on the air content of the lung samples, the value of Δεh was corrected for the air content of each sample as determined by the point-counting method in the area where the time domain reflectometry data were obtained. The lungs of rats that received an injection of oleic acid had a significantly increased free water content [(Δεh of lung/Δε of pure water) × density of pure water] compared with that in the normal lung (0.76 vs. 0.59 g/cm3). These results indicate that free water occupies ∼60% of the total volume of normal lung tissue and that there is an increase in free water in pulmonary edema.

Plasma branched-chain amino acid levels and muscle energy metabolism in patients with chronic obstructive pulmonary disease

BACKGROUND & AIMS Although several studies have shown that plasma concentrations of branched-chain amino acids (BCAAs) are reduced in patients with chronic obstructive pulmonary disease (COPD), little is understood about how low concentrations of BCAAs limit exercise in such patients. The present study investigated whether plasma BCAAs are related to energy metabolism in exercising muscle using (31)P-magnetic resonance spectroscopy (MRS). METHODS We analyzed the plasma amino acid profiles of 23 male patients with COPD (aged 69.2+/-5.1 years) and of 7 healthy males (aged 64.1+/-6.0 years). We normalized the exercise intensity of repetitive lifting by adjusting the weight to 7% of the maximal grip power. The intracellular pH and the phosphocreatine (PCr) index (PCr/(PCr+Pi); Pi, inorganic phosphate) were calculated from MR spectra. We evaluated the relationship between intracellular pH and PCr index at the completion of exercise and the plasma BCAA concentration. RESULTS Glutamine concentrations were elevated in patients with COPD compared with healthy individuals. Plasma concentrations of BCAAs correlated with intracellular pH and PCr index at the completion of exercise. CONCLUSIONS The findings are consistent with the notion that BCAAs affect muscle energy metabolism during exercise in patients with COPD.

Implication of ESR signals from ceruloplasmin (Cu2+) and transferrin (Fe3+) in pleural effusion of lung diseases

Pleural effusions of seven lung cancer patients (mean age; 58) and seven non-cancer patients (mean age; 49) were examined and Cu(2+) was measured in ceruloplasmin and Fe(3+) in transferrin signals by electron spin resonance (ESR) method. The variations of total Fe and Cu ions, ceruloplasmin and transferrin, proteins, neutrophil cell counts, LDH and nitrite/nitrate were also examined. The Cu(2+) peak was decreased and the Fe(3+) peak was increased in the cancer group. The interrelationship among Cu(2+), total Cu and ceruloplasmin, and among Fe(3+), total Fe and transferrin clarified that Cu(2+) and Fe(3+) are not a representative of ceruloplasmin and transferrin, respectively. The ratio of Cu(2+)/Fe(3+) in pleural effusion distinguished lung cancer from benign inflammation as a cause. The ratio of total Cu/total Fe measured by the chemical analysis method also distinguished these, but the ratio of ceruloplasmin/transferrin was unable to distinguish the cancer. In conclusion, the simple and rapid measurement of Cu(2+)/Fe(3+) by ESR effectively abstracts the variation of total ion concentrations caused by malignant disease.

In vivo Hahn spin-echo decay (Hahn-T2) observation of regional changes in the time course of oleic acid lung injury.

We studied the time course of changes in the Hahn spin‐echo decay (Hahn‐T2) in lungs of spontaneously breathing living rats at 1 hour, 3 hours, and 7 days following oleic acid injection. Motion artifacts were minimized by using the motion‐insensitive interleaved rapid line scan (ILS) imaging technique. Prior to injury, the lungs exhibited two resolvable exponential Hahn‐T2 components. One and 3 hours after injury the decay showed a regionally nonuniform behavior, which was fit with one, two, or three exponential components. The short and medium components increased at 1 and 3 hours after injection. The third, much longer, component is probably due to intraalveolar pulmonary edema. After 7 days the Hahn decay was similar to that observed before injury, probably reflecting resolution of the edema. Our data suggest that Hahn‐T2 measurements can be used to characterize the time course and regional distribution of lung injury in living animals. J. Magn. Reson. Imaging 2000;11:215–222.