Characteristics of inspiratory and expiratory reactance in interstitial lung disease.

BACKGROUND: Forced oscillometry is a non-invasive method to measure respiratory resistance and reactance. In this study, we investigated the characteristics of measurements obtained with an impulse oscillation system (IOS) for patients with interstitial lung disease (ILD). METHOD: IOS and spirometry were performed in 64 ILD patients, 54 asthma patients, 49 chronic obstructive pulmonary disease (COPD) patients, and 29 controls. Respiratory resistance and reactance were assessed as measurements averaged over several tidal breaths (whole-breath analysis) and as measurements separately averaged during inspiration and expiration (inspiratory-expiratory analysis). RESULTS: Whole-breath IOS analyses for ILD patients showed increased resistance at 5 Hz and decreased reactance at 5 Hz (X5) compared with controls, although these features were also found in asthma and COPD patients. Inspiratory-expiratory analysis demonstrated that the changes in X5 and reactance area (AX) between inspiration and expiration (ΔX5 and ΔAX, respectively) were significantly different from those in asthma patients, COPD patients, and controls. However, multiple linear regression analysis showed that the presence of ILD was independently associated with ΔX5, but not with ΔAX. Furthermore, ΔX5 was inversely correlated with vital capacity and diffusing capacity of carbon monoxide in ILD patients. CONCLUSIONS: Our results suggest that ΔX5 is a characteristic feature of IOS measurements in ILD patients, which is clearly different from those in asthma and COPD patients. This within-breath X5 change in ILD might be associated with its severity and physiological abnormality, although further studies are needed to investigate its cause.

The intercomparison of cosmic rays with heavy ion beams at NIRS (ICCHIBAN) project.

The ICCHIBAN-2 experiment, the first dedicated to the ground-based intercomparison of passive space dosemeters, was carried out between 23 May and 28 May 2002 at the National Institute of Radiological Sciences in Chiba, Japan. The primary objective of the ICCHIBAN-2 experiment was to intercompare the response of passive dosemeters used in space crew dosimetry to monoenergetic heavy ions of charge and energy spanning a significant portion of the galactic cosmic ray (GCR) spectrum. During the ICCHIBAN-2 experiment, dosemeters from 12 different laboratories in 9 countries were irradiated under identical conditions to heavy ion beams of 150 MeV n(-1) (4)He, 400 MeV n(-1) (12)C, 490 MeV n(-1) (28)Si and 500 MeV n(-1) (56)Fe at the NIRS Heavy Ion Medical Accelerator.

Reduction in life span of normal human fibroblasts exposed to very low-dose-rate charged particles.

We studied the effect of chronic low-dose irradiation with heavy ions on the life span of normal human fibroblasts in vitro. Cells were cultured in a CO2 incubator that was placed in the irradiation room for biological studies of heavy ions in the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences (NIRS) and were exposed to scattered radiations produced by heavy-ion beams for the life span of the cell population. The absorbed dose, which was measured using a thermoluminescence dosimeter (TLD) and a silicon semiconductor detector, was 1.4 mGy per day when the HIMAC was operated for biological experiments. The total number of population doublings of the exposed cells as reduced to 79-93% of that of nonexposed control cells. However, the life span of cells exposed to low-dose 137Cs gamma rays (approximately 1 mGy/day) in the CO2 incubator in the gamma-irradiation room in NIRS was prolonged to 104-106% of that of nonexposed control cells. Thus there is evidence that exposure to chronic low-dose heavy-ion radiation reduces the life span of cells.

Differential absorbed dose distributions in lineal energy for neutrons and gamma rays at the mono-energetic neutron calibration facility.

Absorbed dose distributions in lineal energy for neutrons and gamma rays of mono-energetic neutron sources from 140 keV to 15 MeV were measured in the Fast Neutron Laboratory at Tohoku University. By using both a tissue-equivalent plastic walled counter and a graphite-walled low-pressure proportional counter, absorbed dose distributions in lineal energy for neutrons were obtained separately from those for gamma rays. This method needs no knowledge of energy spectra and dose distributions for gamma rays. The gamma-ray contribution in this neutron calibration field >1 MeV neutron was <3%, while for <550 keV it was >40%. The measured neutron absolute absorbed doses per unit neutron fluence agreed with the LA150 evaluated kerma factors. By using this method, absorbed dose distributions in lineal energy for neutrons and gamma rays in an unknown neutron field can be obtained separately.

Experimental microdosimetric distributions of protons, from 19 to 65 MeV, using an A150-walled Low Pressure Proportional Counter.

Microdosimetric distributions of protons, from 19 to 65 MeV, were measured using an A150-walled Low Pressure Proportional Counter at the cyclotron facility in the National Institute of Radiological Sciences. The measured distributions were found to be very different from the spectra assumed by the Continuous Slowing Down Approximation. The measurements consisted of determining the energy deposition by direct incident protons, by secondary electrons produced in the wall of the detector and by scattered protons at the wall. The secondary electron and the scattered proton distributions were studied using analytical functions and the MCNPX Monte Carlo code, respectively.

Efficiency of a radiophotoluminescence glass dosemeter for low-earth-orbit space radiation.

Chips of a radiophotoluminescence glass dosemeter (RPLG) were used for measurements of space radiation during a 9.8 d Shuttle-Mir mission (STS-91) at an altitude of 400 km and an inclination of 51.65 degrees. Two of RPLG chips were put into each of 59 positions in or on a life-size human phantom. The RPLG values equivalent to 137Cs gamma ray absorbed doses were found to be systematically lower than those of a Mg2SiO4:Tb thermoluminescence dosemeter (TDMS). In comparison with the organ or tissue absorbed dose and dose equivalent values that were estimated using a combination of TDMS and plastic nuclear track detectors, the efficiencies of the RPLG chips were about 80% for the water absorbed dose and about 40% for the dose equivalent. Whereas the percentage values will change during different missions, such additional information obtained from small RPLG chips is useful for improving the reliability of radiation dosimetry in space.

KL-6 as an indicator for lymphocytic interstitial pneumonia (LIP) in a human T-lymphotrophic virus type 1 (HTLV-1) carrier.

A 59-year-old woman was admitted to our hospital complaining of a productive cough, dyspnea on effort, and low-grade fever. Although chest X-rays showed no marked abnormalities, her level of serum KL-6 was extremely high. We therefore suspected the presence of interstitial pneumonia. High-resolution computed tomography (CT) scan revealed infiltrative shadows in S6 of the right lung, and her serum was positive for antihuman T-lymphotropic virus type 1 (HTLV-1) antibodies. From the clinical symptoms, radiographic findings, and histological findings, the diagnosis was probable lymphocytic interstitial pneumonia (LIP). After high-dose corticosteroid therapy, the level of serum KL-6 decreased rapidly. We conclude that KL-6 is a convenient and reliable marker for evaluating the activity of pulmonary manifestations in HTLV-1 carriers and that it is especially useful in monitoring the effectiveness of treatments.

Microdosimetric distribution of protons, Ep = 19-65 MeV, measured with a low pressure proportional counter.

Microdosimetric measurements of 19, 32, 43, 55, and 65 MeV protons were carried out with the A-150-walled low pressure proportional counter (LPPC). The spectra are deconvoluted into three components, which are energy loss by directly incident protons, secondary electrons, and scattered protons and heavy charged particle (including protons) produced by proton nuclear reactions with the TE wall. Dose-mean lineal energies of protons are large as usual, because larger lineal energies by proton reaction events are affected.

Calibration results obtained with Liulin-4 type dosimeters.

The Mobile Radiation Exposure Control System's (Liulin-4 type) main purpose is to monitor simultaneously the doses and fluxes at 4 independent places. It can also be used for personnel dosimetry. The system consists of 4 battery-operated 256-channel dosimeters-spectrometers. We describe results obtained during the calibrations of the spectrometers at the Cyclotron facilities of the University of Louvain, Belgium and of the National Institute of Radiological Sciences-STA, Chiba, Japan with protons of energies up to 70 MeV. The angular sensitivities of the devices are studied and compared with Monte-Carlo predictions. We also present the results obtained at the HIMAC accelerator with 500 MeV/u Fe ions and at the CERN high energy radiation reference fields. Records made during airplane flights are shown and compared with the predictions of the CARI-6 model.

Solid-state integrating detectors as an indicator of biological doses from HZE particles.

For interpretation of results obtained in future biological experiments in the International Space Station (ISS), biologically equivalent doses have to be determined using small-scale detectors without disturbing the surrounding radiation field. The detectors should be lightweight, stable, safe, and simple in handling. Solid-state integrating detectors (SSID) can satisfy these requirements. This paper demonstrates that combination of SSID such as thermoluminescence dosimeters and radiophotoluminescence glasses can be practically used for the evaluation of biologically equivalent doses. Statistical errors (type-A uncertainty) of this method will be satisfactorily small relative to those generally observed in biological responses. Permissible levels of systematic errors (type-B uncertainty) depend on dosimetry purposes (most-probable or conventional) and variability of biological responses.

Probability of cell hits in selected organs and tissues by high-LET particles at the ISS orbit.

The fluence of high-LET particles (HLP) with LET infinity H2O greater than 15 keV micrometers-1 in selected organs and tissues were measured with plastic nuclear track detectors using a life-size human phantom on the 9th Shuttle-Mir Mission (STS-91). The planar-track fluence of HLP during the 9.8-day mission ranged from 1.9 x 10(3) n cm-2 (bladder) to 5.1 x 10(3) n cm-2 (brain) by a factor of 2.7. Based on these data, a probability of HLP hits to a matured cell of each organ or tissue was roughly estimated for a 90-day ISS mission. In the calculation, all cells were assumed to be spheres with a geometric cross-sectional area of 500 micrometers2 and the cell-hit frequency from isotropic space radiation can be described by the Poisson-distribution function. As results, the probability of one or more than 1 hit to a single cell by HLP for 90 days ranged from 17% to 38%; that of two or more than 2 hits was estimated to be 1.3-8.2%.

Syndrome of inappropriate secretion of ADH (SIADH) following cisplatin administration in a pulmonary adenocarcinoma patient with a malignant pleural effusion.

We report a patient with pulmonary adenocarcinoma complicated by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) following systemic chemotherapy with cisplatin (CDDP) and vindesine (VDS). A 66-year-old woman was diagnosed as having pulmonary adenocarcinoma with malignant pleural effusion following investigations for cough and dyspnea. After drainage of the effusion she received combination chemotherapy with CDDP and VDS. She developed SIADH 48 hours following chemotherapy. Interestingly, the use of carboplatin (CBDCA) and VDS in the subsequent treatment course was well tolerated indicating that the SIADH was most likely to have been induced by administration of CDDP.

Induction of cytochrome P450 3A4 by docetaxel in peripheral mononuclear cells and its expression in lung cancer.

Several recent studies have demonstrated that the cytochrome p450 (CYP) family plays an important role in the metabolism of taxanes. However, the role of CYP gene expression in tumors and peripheral mononuclear cells (PMN) is unknown. We therefore investigated the levels of CYP3A4 and CYP2C gene expression using reverse transcription polymerase chain reaction (RT-PCR) in PMN from 16 previously untreated lung cancer patients to determine whether the expression of the two genes is induced by docetaxel (TXT). Neither the CYP3A4 nor the CYP2C gene was induced after administration of carboplatin (CBDCA) alone. Expression of the CYP3A4 gene was induced by the administration of TXT alone or TXT and CBDCA, but expression of the CYP2C gene was unaffected. We also measured the expression of both genes using RT-PCR in 20 autopsy samples (ten non-small-cell lung cancers and their corresponding normal lung tissues) obtained from patients who had not received any chemotherapy during life. The level of CYP2C gene expression in samples of lung cancer was significantly higher than in normal lung tissue, but the level of CYP3A4 gene expression was not. These results suggest that the CYP3A4 gene is induced by TXT, and that it plays an important role in intracellular TXT metabolism.

Responses of TLD-BeO:Na (UD-170A) to heavy ions and space radiation.

Responses of TLD-BeO:Na (UD-170A) to high-LET particles were examined with selected heavy ion beams (He, C, Ne, Ar, and Kr) at NIRS-HIMAC, and compared with TLD-Mg2SiO4:Tb (TLMS) and radiophotoluminescent glass (RPLG). The relative TL efficiency of UD-170A as 137Cs gamma ray equivalent arose notably with increasing LET infinity.H2O for He and C, and decreased for the heavier charged particles. In contrast, the efficiencies of TLMS and RPLG did not increase over the range of LET from 0.5 to 410 keV.micron-1. The three detectors were used for space radiation measurement in the Mir space station for 40 days at 400 km altitude and 51.65 degrees inclination. The values from each detector as gamma ray absorbed dose equivalent showed a large spatial variation by a factor 2 in the same Core module. The detector values were in the order of UD-170A > TLMS > RPLG as expected from the results obtained on the ground, although ratios of these values changed depending on positions. These results indicate that both radiation quality and dose level in a spacecraft change significantly and a measurement at one location cannot accurately represent the individual dose to an astronaut. These small detectors should be useful as supplementary personal dosemeters for astronauts.

SGLT gene expression in primary lung cancers and their metastatic lesions.

Cancer cells show increased glucose uptake and utilization in comparison with their normal counterparts. Glucose transporters play an important role in glucose uptake. We previously reported the differential gene expression of the GLUT family in primary and metastatic lesions of lung cancer. To investigate the role of Na( +) / glucose cotransporter (SGLT) genes in cancers, we examined the levels of expression of SGLT1 and SGLT2 genes in primary lung cancers and their metastatic lesions. Ninety-six autopsy samples (35 primary lung cancers, 35 corresponding normal lung tissues, 10 metastatic liver lesions, and 16 metastatic lymph nodes) from 35 patients were analyzed for SGLT1 and SGLT2 expression by reverse transcription (RT)-polymerase chain reaction (PCR). There were no significant differences in the level of expression of either gene between the primary lung cancers and normal lung tissues. The level of SGLT1 expression in the metastatic lesions and primary lung cancers did not differ significantly. The level of SGLT2 expression was, however, significantly higher in the metastatic lesions of both the liver and lymph node than in the primary lung cancers. These results suggest that SGLT2 plays a role in glucose uptake in the metastatic lesions of lung cancer.

Association between expression of the MRP3 gene and exposure to platinum drugs in lung cancer.

To investigate the roles played by the multidrug resistance-associated protein (MRP1) homologues MRP3 and MRP4 in resistance to platinum drugs, we examined steady-state levels of mRNA for both MRP3 and MRP4 in normal lung and lung cancer specimens as well as peripheral mononuclear cells (PMN) after platinum drug exposure. MRP3 and MRP4 gene expression levels were monitored in the PMN of 10 previously untreated lung cancer patients within 24 hr after carboplatin (CBDCA) administration. Expression levels for both genes were also examined in 80 autopsy samples (40 primary tumors and 40 corresponding normal lung tissues) from 40 patients with lung cancer. MRP3 and MRP4 gene expression levels were assessed by quantitative reverse transcription-polymerase chain reaction. MRP3 expression levels in the PMN rose rapidly within 24 hr after administration of CBDCA, whereas MRP4 expression levels remained the same. Furthermore, MRP3 expression levels in normal lung and tumor tissues from autopsy samples that had been exposed to platinum drugs while the patients were alive were significantly higher than those in unexposed tissues, but again MRP4 expression levels remained the same. These results suggest that platinum drugs and/or the physiological stress response to xenobiotics induce expression of the MRP3 gene.

Cosmic radiation protection dosimetry using an Electronic personal Dosemeter (Siemens EPD) on selected international flights.

The effectiveness of an Electronic Personal Dosemeter (Siemens EPD) for cosmic-radiation dosimetry at aviation altitudes was examined on eight international flights between March and September, 1998. The EPD values (Hepd) of the dose equivalent from penetrating radiation, Hp(10), were assumed to be almost the same as the electron absorbed doses during those flights. Based on the compositions of cosmic radiation in the atmosphere and the 1977 ICRP recommendation, an empirical equation to conservatively estimate the personal dose equivalent (Hp77) at a depth of 5 cm was derived as Hp77 = 3.1 x Hepd. The personal dose equivalent (Hp90) based on the 1990 ICRP recommendation was given by Hp90 = 4.6 x Hepd; the conservative feature of Hp90 was confirmed in a comparison with the calculated effective doses by means of the CARI-6 code. It is thus expected that the EPD will be effectively used for radiation protection dosimetry on selected international flights.

[A case of lung adenocarcinoma showing diffuse air-space consolidation with idiopathic interstitial pneumonia].

Routine chest radiography demonstrated abnormal opacities in the right lower lung field of a 54-year-old man with idiopathic interstitial pneumonia. A high-resolution chest CT scan showed diffuse air-space consolidation in the right lower lung with replacement of a honeycomb area. The diagnosis was adenocarcinoma, and a right lower lobectomy was performed. Histopathologic examination showed moderately differentiated adenocarcinoma and the pathological stage was T3 N0 M0 (Stage IIB). About 1 year later, the cancer recurred with diffuse air-space consolidation in the whole of the right lung and the left middle and lower lung, which resulted in the patient's death. It was difficult to discriminate between an acute change for the worse of idiopathic interstitial pneumonia and a recurrence of lung cancer on the basis of the CT findings in this patient. It is important to elucidate the CT features of lung cancer associated with idiopathic interstitial pneumonia.