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Intravascular large B-cell lymphoma (IVLBCL) typically involves nonspecific symptoms that complicate diagnosis. This report discusses the case of a 70-year-old man, who presented with dyspnea, fatigue, and weight loss that evolved into severe respiratory failure, diagnosed with IVLBCL via random skin biopsy. The initial improvement in respiratory symptoms was followed by coronavirus disease. Response to steroid therapy and elevated lactate dehydrogenase levels suggested IVLBCL, confirmed by a random skin biopsy. The combination chemotherapy of rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone improved the respiratory condition. This case highlights the diagnostic challenges associated with IVLBCL and the crucial role of random skin biopsy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The quantitative measurement of free radicals in liquid using an X-band electron paramagnetic resonance (EPR) was systematized. Quantification of free radicals by EPR requires a standard sample that contains a known spin amount/concentration. When satisfactory reproducibility of the sample material, volume, shape, and positioning in the cavity for EPR measurements can be guaranteed, a sample tested and a standard can be directly compared and the process of quantification can be simplified. The purpose of this study was to simplify manual quantitative EPR measurement. A suitable sample volume for achieving a stable EPR intensity was estimated. The effects of different solvents on the EPR sensitivity were compared. The stability and reproducibility of the EPR intensity of standard nitroxyl radical solutions were compared among different types of sample tubes. When the sample tubes, sample volumes, and/or solvents were the same, the EPR intensity was reproduced with an error of 2% or less for μM samples. The quantified sample and the standard sample in the same solvent and the same volume drawn into the same sample tube was able to be directly compared. The standard sample for quantification should be measured just before or after every daily experiment., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2022 JCBN.)

Linear energy transfer (LET) dependence of yields of O 2 -dependent and O 2 -independent hydrogen peroxide (H 2 O 2 ) in water irradiated by ionizing radiation was investigated. The radiation-induced hydroxyl radical (•OH) generation in an aqueous solution was reported to occur in two different localization densities, the milli-molar (relatively sparse) and/or molar (markedly-dense) levels. In the milli-molar-level •OH generation atmosphere, •OH generated at a molecular distance of ∼7 nm are likely unable to interact. However, in the molar-level •OH generation atmosphere, several •OH were generated with a molecular distance of 1 nm or less, and two •OH can react to directly make H 2 O 2 . An aliquot of ultra-pure water was irradiated by 290-MeV/nucleon carbon-ion beams at the Heavy-Ion Medical Accelerator in Chiba (HIMAC, NIRS/QST, Chiba, Japan). Irradiation experiments were performed under aerobic or hypoxic (<0.5% oxygen) conditions, and several LET conditions (13, 20, 40, 60, 80, or >100 keV/μm). H 2 O 2 generation in irradiated samples was estimated by three methods. The amount of H 2 O 2 generated per dose was estimated and compared. O 2 -independent H 2 O 2 generation, i.e. H 2 O 2 generation under hypoxic conditions, increased with increasing LET. On the other hand, the O 2 -dependent H 2 O 2 generation, i.e. subtraction of H 2 O 2 generation under hypoxic conditions from H 2 O 2 generation under aerobic conditions, decreased with increasing LET. This suggests that the markedly-dense •OH generation is positively correlated with LET. High-LET beams generate H 2 O 2 in an oxygen-independent manner.

Relatively young (4-week-old) selenium deficient (SeD) mice, which lack the activity of selenium-dependent glutathione peroxidase (GSH-Px) isomers, were prepared using torula yeast-based SeD diet. Mice were fed the torula yeast-based SeD diet and ultra-pure water. Several different timings for starting the SeD diet were assessed. The weekly time course of liver comprehensive GSH-Px activity after weaning was monitored. Protein expression levels of GPx1 and 4 in the liver were measured by Western blot analysis. Gene expression levels of GPx1, 2, 3, 4, and 7 in the liver were measured by quantitative real-time PCR. Apoptotic activity of thymocytes after hydrogen peroxide (H 2 O 2 ) exposure was compared. Thirty-day survival rates after whole-body X-ray irradiation were estimated. Pre-birth or right-after-birth starting of the SeD diet in dams was unable to lead to creation of SeD mice due to neonatal death. This suggests that Se is necessary for normal birth and healthy growing of mouse pups. Starting the mother on the SeD diet from 2 weeks after giving birth (SeD-trial-2w group) resulted in a usable SeD mouse model. The liver GSH-Px activity of the SeD-trial-2w group was almost none from 4 week olds, but the mice survived for more than 63 weeks. Protein and gene expression of GPx1 was suppressed in the SeD-trial-2w group, but that of GPx4 was not. The thymocytes of the SeD-trial-2w group were sensitive to H 2 O 2 -induced apoptosis. The SeD-trial-2w group was sensitive to whole-body X-ray irradiation compared with control mice. The SeD-trial-2w model may be a useful animal model for H 2 O 2 /hydroperoxide-induced oxidative stress., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2021 JCBNCopyright © 2021 JCBN.)

The reaction properties of the thiol compounds, cysteine (Cys), N -acetyl-l-cysteine (NAC), the reduced form glutathione (GSH), and homocysteine (HCS) were compared. The main purpose of this study was to find a thiol-based anti-oxidant suitable for biological experiments and to provide clear reasoning for its selection. The availability of thiol compounds to generate superoxide by reducing molecular oxygen (O 2 ) at a hyperthermal temperature was discussed. An oxidative atmosphere, i.e., superoxide generation by the hypoxanthine-xanthine oxidase reaction, hydroxyl radical generation by X-ray irradiation, or direct one-electron oxidation by ferricyanide, was prepared in a reaction mixture containing 0.1 mM TEMPOL and 1 mM test compound, and the EPR signal decay of TEMPOL was observed. A reaction mixture containing 0.1 mM TEMPOL and 1 mM thiol compound was incubated at 44°C, and the EPR signal decay of TEMPOL was observed. Thiols could function as H-donors to the oxoammonium cation and produce the hydroxylamine form of TEMPOL in an oxidative atmosphere. Thiols could also irreversibly react with the oxoammonium cation. GSH and Cys could reduce O 2 to form superoxide/hydroperoxyl radical at hyperthermal temperatures, but HCS and NAC could not reduce O 2 . GSH and Cys may cause reductive stress, whereas NAC is a simple tractable antioxidant., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2019 JCBN.)

The amounts of reactive oxygen species generated in aqueous samples by irradiation with X-ray or clinical carbon-ion beams were quantified. Hydroxyl radical ( • OH), hydrogen peroxide (H 2 O 2 ), and the total amount of oxidation reactions, which occurred mainly because of • OH and/or hydroperoxy radicals (HO 2 • OH generation was expected to be localized on the track/range of the carbon-ion beam/X-ray, and mM and M levels of • OH generation was expected to be localized on the track/range of the carbon-ion beam/X-ray, and mM and M levels of • OH generation were observed. Total • OH generation levels were identical at the same dose irrespective of whether X-ray or carbon-ion beam irradiation was used, and were around 0.28-0.35 µmol/L/Gy. However, sparse • OH generation levels decreased with increasing linear energy transfer, and were 0.17, 0.15, and 0.09 µmol/L/Gy for X-ray, 20 keV/µm carbon-ion beam, and >100 keV/µm carbon-ion beam sources, respectively. H 2 O 2 generation was estimated as 0.26, 0.20, and 0.17 µmol/L/Gy, for X-ray, 20 keV/µm carbon-ion beam, and >100 keV/µm carbon-ion beam sources, respectively, whereas the ratios of H 2 O 2 generation per oxygen consumption were 0.63, 0.51, and 3.40, respectively. The amounts of total oxidation reactions were 2.74, 1.17, and 0.66 µmol/L/Gy, respectively. The generation of reactive oxygen species was not uniform at the molecular level.

The reactivity of nitroxyl free radicals, 4-hydroxyl-2,2,6,6-tetramethylpiperidine- N -oxyl (TEMPOL) and 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine- N -oxyl (CmP), with reactive oxygen species (ROS) were compared as typical 6-membered and 5-membered ring nitroxyl compounds, respectively. The reactivity of the hydroxylamine forms of both these nitroxyl radicals (TEMPOL-H and CmP-H) was also assessed. Two free radical species of ROS, hydroxyl radical ( • OH) and superoxide (O 2 •- ), were subjected to a competing reaction. • OH was generated by UV irradiation from an aqueous H 2 O 2 solution (H 2 O 2 -UV system), and O 2 •- was generated by a reaction between hypoxanthine and xanthine oxidase (HX-XO system). • OH and O 2 •- generated by the H 2 O 2 -UV and HX-XO systems, respectively, were measured by electron paramagnetic resonance (EPR) spin-trapping, and the amount of spin adducts generated by each system was adjusted to be equal. The time courses of the one-electron oxidation of TEMPOL, CmP, TEMPOL-H, and CmP-H in each ROS generation system were compared. A greater amount of TEMPOL was oxidized in the HX-XO system compared with the H 2 O 2 -UV system, whereas the reverse was observed for CmP. Although the hydroxylamine forms of the tested nitroxyl radicals were oxidized evenly in the H 2 O 2 -UV and HX-XO systems, the amount of oxidized CmP-H was approximately 3 times greater compared with TEMPOL-H., Competing Interests: No potential conflicts of interest were disclosed.

The glutathione (GSH)-mediated superoxide (O 2 •- ) generation in an aqueous solution and relation of hydrogen peroxide (H 2 O 2 ) and effect of catalase were investigated. GSH-induced O 2 •- generation in hyperthermal temperatures was measured by the nitroblue tetrazolium (NBT) mehod. Heating an aqueous solution containing GSH caused superoxide from dissolved O 2 . H 2 O 2 was generated simultaneously in this reaction mixture probably from the hydroperoxy radical (HO 2 • ), which is equilibrated with O 2 •- in an aqueous condition, and then H 2 O 2 consumed O 2 •- . Coexisting catalase in the reaction mixture, as a result, could increase O 2 •- generation. The catalase-exaggerated extracellular O 2 •- generation could give a harmful effect to living cells. This GSH-induced oxidative stress can be a part of mechanisms of hyperthermia therapy., Competing Interests: No potential conflicts of interest were disclosed.

Oral mucositis (OM) is a common and painful complication of radiotherapy for head and neck cancer. Hangeshashinto (HST), a Japanese traditional medicine, is known to alleviate radiotherapy- and/or chemotherapy-induced OM; however, the detailed mechanism has not yet been clarified. The aim of the present study was to clarify the details of the antioxidative functions of HST against reactive oxygen species (ROS) produced by radiation. The hydroxyl radical (•OH)-scavenging ability and the reduction ability was simultaneously measured using a modified electron paramagnetic resonance (EPR) spin-trapping method. The superoxide (O(2) (•-))-scavenging ability was estimated by an EPR redox probing method. Water suspensions of powdered HST and of its seven constitutive crude drugs were tested. In addition, some of the main water-soluble ingredients of the crude drugs were also tested. HST was found to scavenge both •OH and O(2) (•-). Furthermore, HST was observed to reduce relatively stable nitroxyl radicals. Glycyrrhizae Radix (kanzo), Ginseng Radix (ninjin), Zizyphi Fructus (taiso) and glycyrrhizin (an ingredient of kanzo) were all found to be relatively good •OH scavengers. Scutellariae Radix (ogon) and Coptidis Rhizoma (oren) demonstrated reducing ability. In addition, acteoside and berberine chloride, which are water-soluble ingredients of ogon and oren, respectively, also demonstrated reducing ability. Oren exhibited oxidative ability at higher concentrations, which may have a function in maintaining catalytic redox action. The antioxidative function of HST probably worked via a balance of scavenging ROS, reducing stable free radicals, and some minor oxidizing activities., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

The scavenging activity of rat plasma against hyperthermia-induced reactive oxygen species was tested. The glutathione-dependent reduction of a nitroxyl radical, 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, which was restricted by adding superoxide dismutase or by deoxygenating the reaction mixture, was applied to an index of superoxide (O2 (•-)) generation. A reaction mixture containing 0.1 mM 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl and 1 mM glutathione was prepared using 100 mM phosphate buffer containing 0.05 mM diethylenetriaminepentaacetic acid. The reaction mixture was kept in a screw-top vial and incubated in a water bath at 37 or 44°C. The time course of the electron paramagnetic resonance signal of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl in the reaction mixture was measured by an X-band EPR spectrometer (JEOL, Tokyo, Japan). When the same experiment was performed using rat plasma instead of 100 mM PB, the glutathione-dependent reduction of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, i.e., generation of O2 (•-), was not obtained. Only the first-order decay reduction of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, which indicates direct reduction of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, was obtained in rat plasma. Adding 0.5% albumin to the phosphate buffer reaction mixture could almost completely inhibit O2 (•-) generation at 37°C. However, addition of 0.5% albumin could not inhibit O2 (•-) generation at 44°C, i.e., hyperthermic temperature. Ascorbic acid also showed inhibition of O2 (•-) generation by 0.01 mM at 37°C, but 0.02 mM or more could inhibit O2 (•-) generation at 44°C. A higher concentration of ascorbic acid showed first-order reduction, i.e., direct one-electron reduction, of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl. Hyperthermia-induced O2 (•-) generation in rat plasma can be mostly inhibited by albumin and ascorbic acid in the plasma.

Temperature-dependent free radical reactions were investigated using nitroxyl radicals as redox probes. Reactions of two types of nitroxyl radicals, TEMPOL (4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl) and carbamoyl-PROXYL (3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl), were tested in this paper. Heating a solution containing a nitroxyl radical and a reduced form of glutathione (GSH) caused temperature-dependent decay of electron paramagnetic resonance (EPR) signal of the nitroxyl radical. Heating a solution of the corresponding hydroxylamine form of the nitroxyl radical showed EPR signal recovery. The GSH-dependent reduction of nitroxyl radicals at 70°C was suppressed by antioxidants, spin trapping agents, and/or bubbling N(2) gas, although heating carbamoyl-PROXYL with GSH showed temporarily enhanced signal decay by bubbling N(2) gas. Since SOD could restrict the GSH-dependent EPR signal decay of TEMPOL, O(2) (•-) is related with this reaction. O(2) (•-) was probably generated from dissolved oxygen in the reaction mixture. Oxidation of the hydroxylamines at 70°C was also suppressed by bubbling N(2) gas. Heating a solution of spin trapping agent, DMPO (5,5-dimethyl-1-pyrroline-N-oxide) showed a temperature-dependent increase of the EPR signal of the hydroxyl radical adduct of DMPO. Synthesis of hydroxyl radical adduct of DMPO at 70°C was suppressed by antioxidants and/or bubbling N(2) gas. The results suggested that heating an aqueous solution containing oxygen can generate O(2) (•-).

We previously showed that free radicals and oxidative stress are involved in radiation-induced skin reactions. Since vitamin E (VE) is a particularly important lipophilic antioxidant, VE-deficient mice were used to examine its effects on radiation-induced skin damage. The VE content of the skin was reduced to one fourth of levels of normal mice. Neither the time of onset nor the extent of the reactions quantified with a scoring system differed between normal and VE-deficient mice after local X-irradiation (50 Gy). Similarly, there was no difference in the levels of the ascorbyl radical between the groups, although they were higher in irradiated skin than non-irradiated skin. X-irradiation increased the amount of Bax protein in the skin of normal mice both in the latent and acute inflammatory stages, time- and dose-dependently. The increase was associated with an increase in cytochrome c in the cytosolic fraction, indicating that apoptosis was also promoted by the irradiation. The increase in Bax protein correlated well with the thickness of the skin. Although a deficiency in VE should lower resistance to free radicals in the mitochondrial membrane and thus enhance radiation-induced Bax expression and apoptosis, it actually attenuated the increase in Bax protein caused by irradiation.

We investigated the amount and distribution of hydrogen peroxide (H(2)O(2)) generated in a solid gelatin sample irradiated by heavy ion (carbon) beam. We irradiated the gelatin sample, which contained a nitroxyl radical (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl, TEMPOL), with a 290-MeV/nucleon carbon beam (~128 Gy). To verify the distribution of H(2)O(2) generation in the irradiated sample, we employed both electron paramagnetic resonance (EPR) spectroscopic and magnetic resonance (MR) imaging methods based on H(2)O(2)-dependent paramagnetic loss of TEMPOL. We obtained a distribution profile of the H(2)O(2)-dependent reaction in the gelatin sample when we irradiated gelatin samples with carbon beams with several different linear energy transfer (LET) values. Because the profiles of oxygen consumption in the gelatin sample measured by L-band EPR oxymetry and of the H(2)O(2)-dependent reaction have almost the same shape, the profile of the H(2)O(2)-dependent reaction can be used as an estimation of the profile of the generation of H(2)O(2). The H(2)O(2) profile in one intact gelatin sample scanned by 7-tesla MR imaging showed a similar shape as a result of the EPR experiment. We obtained several hundreds of micromolars of H(2)O(2) generated in a gelatin sample irradiated by carbon beam when 200 Gy was given at the surface of the sample. H(2)O(2) distribution was almost flat, with only a slight peak just before the end of the beam.

Quantitative detection of free radical reactions induced by low linear-energy-transfer (LET) irradiation in an aqueous solution was attempted using nitroxyl radicals. The stability and reactivity of reaction mixtures containing a nitroxyl radical and a hydrogen donor, i.e., glutathione (GSH), nicotinamide adenine dinucleotide (NADH), or nicotinamide adenine dinucleotide phosphate (NADPH), were tested. X-band electron paramagnetic resonance (EPR) measurements of several reaction mixtures were performed to find a suitable preparation to quantitatively detect free radical reactions produced by low LET irradiation. The EPR signal intensity of nitroxyl radicals was decreased by low LET irradiation when a hydrogen donor coexisted in the reaction mixture. The combination of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (4-hydroxy-TEMPO, known as TEMPOL) and GSH was most preferable among other preparations tested in this paper, because of the sensitivity and irreversible reaction. The extent of the free radical reaction, i.e., formation of reactive oxygen species, in the reaction mixture depended on the radiation energy when an identical dose was given.

In vivo radioprotection of C3H mice by i.p. administration of Zn-, Mn-, Cu-, or Se-containing heat-treated Saccharomyces serevisiae yeast sample was examined. The 30-day survival of the group treated 30 min before 7.5 Gy whole-body X-irradiation with mineral-containing yeast powders suspended in 0.5% methylcellulose was significantly higher than that of control group. When mineral-yeast was administered immediately after irradiation, the survival rate was even higher and Zn- or Cu-yeast showed the highest rate (more than 90%). Although treatment with simple yeast showed a high survival rate (73%), it was significantly lower than that obtained by the Zn-yeast treatment. The effects of Zn-yeast were studied further. When the interval between irradiation and administration was varied, the protective activity of Zn-yeast decreased gradually by increasing the interval but was still significantly high for the administration at 10 h post-irradiation. The dose reduction factor of Zn-yeast (100 mg/kg, i.p. administration immediately after irradiation) was about 1.2. When the suspension of Zn-yeast was fractionated by centrifugation, the insoluble fraction showed a potent effect, while the soluble fraction had only a moderate effect. In conclusion, mineral-yeast, especially Zn-yeast, provides remarkable post-irradiation protection against lethal whole body X-irradiation. The activity is mainly attributable to the insoluble fraction, whereas some soluble components might contribute to the additional protective activity.

Background: Histamine plays an important role in immediate and late immune responses. The histamine type 1 (H1) receptor is expressed on several immune cell populations, but its role in a murine model of asthma remains unclear. The present study evaluated the role of histamine H1 receptors in airway allergic inflammation by comparing the development of bronchial asthma in histamine H1 receptor gene knockout (H1RKO) and wild-type mice., Methods: H1RKO and wild-type mice were sensitized by intraperitoneal injection of ovalbumin (OVA) or saline, and then challenged with aerosolized OVA or saline. Ventilatory timing in response to inhaled methacholine was measured, and samples of blood, bronchoalveolar lavage, and lung tissues were taken 24 h after the last OVA challenge., Results: OVA-treatedwild-type mice showed significantly increased airway eosinophilic infiltration, and airway response to methacholine compared to OVA-treated H1RKO mice. The serum level of immunoglobulin E and levels of interleukin (IL)-4, IL-5, IL-13, and TGF-beta1 in bronchoalveolar lavage fluid were lower in OVA-treated H1RKO mice than in OVA-treated wild-type mice, but there was no significant difference in interferon-gamma expression. Overall, deletion of histamine H1 receptors reduced allergic responses in a murine model of bronchial asthma., Conclusion: Histamine plays an important role via H1 receptors in the development of T helper type 2 responses to enhance airway inflammation.

A 37-year-old male was admitted to our hospital because of abnormal findings seen in a chest radiograph from a physical examination. There was nothing unusual about his past history, and he had been healthy. Chest radiography showed an infiltrative shadow with a cavity in the right upper lobe. A smear test of the sputum was negative but a culture was positive for a mycobacterium, which was identified as M. szulgai. A diagnosis of atypical pulmonary mycobacteriosis caused by M. szulgai. The patient was treated with isoniazid, rifampicin and ethambutol, which gradually improved the infiltration shadow, and his sputum cultures became negative for mycobacteria. In recent years, the frequency of atypical mycobacteriosis has increased up to 10% to 15% of all mycobacterial infections. In Japan, M. avium complex and M. kansasii account for more than 90% of such infections, so other isolates are rare. Most previous cases of atypical mycobacteriosis were secondary infections associated with underlying disease. In this patient, however, we describe a rare case of pulmonary infection due to M. szulgai appearing in a healthy male without underlying disease.

We encountered a patient with a mild fever and chest discomfort in whom right pleural effusion and eosinophilia (48%) had developed. Parasite eggs were found in the feces, and metagonimiasis was diagnosed. The pleural fluid contained many Charcot-Leyden crystals, suggesting active eosinophilic inflammation. Metagonimus yokogawai usually occurs as a gastrointestinal parasite and causes only mild gastrointestinal symptoms such as diarrhea. Most cases of metagonimiasis resolve spontaneously. However, the main manifestation of metagonimiasis in our patient was pleural effusion. Some cases of idiopathic eosinophilic pleural effusion of unknown origin resolve spontaneously, as in our patient. Patients who are therefore considered to have idiopathic pleural effusion may include those with transient parasitic infection.

A house dust bronchial provocation test (BPT) was used to investigate the effect of allergen-induced airway inflammation and airway hyperresponsiveness (AHR) on the level of circulating intracellular adhesion molecule-1 (c-ICAM-1). The concentration of c-ICAM-1 was measured by the sandwich ELISA while the level of eosinophil cationic protein (ECP) in the sputum was determined by RIA. The parameter used for quantification of AHR was the minimum dose of methacholine (Mch) required to produce a fall in respiratory resistance and was expressed as log Dmin. Fourteen subjects with mild atopic asthma participated in this study. Ten patients (dual asthmatic response group; DAR group) developed a late asthmatic response (LAR) following an immediate asthmatic response (IAR). Four subjects (IAR alone group) exhibited only IAR following BPT. In both groups, the mean baseline concentration of c-ICAM-1 did not change 6 h after BPT (from 195.3+/-20.3 to 220.9+/-27.6 and from 215.5+/-23.5 to 231.3+/-30.5 ng/ml, respectively). However, BPT produced a significant increase in the mean concentration of c-ICAM-1 24 h later in the DAR group (257.3+/-41.14 ng/ml, p < 0.05), but not in the IAR alone group (225.5+/-18.1 ng/ml). BPT also increased ECP levels in the sputum from a baseline value 24 h after BPT in the DAR group (from 30.2+/-10.1 to 68.8+/-19.8 ng/ml; p<0.05), but not in the IAR alone group (from 28.1+/-8.3 to 43.3+/-23.7 ng/ml). There was a significant (p<0.05) correlation between c-ICAM-1-concentrations and sputum ECP levels 24 h after BPT in each group. Furthermore an inverse and significant (p<0.05) correlation was found between c-ICAM-1 concentrations and percent changes in log Dmin 24 h after BPT in each group. Our results suggest that increased concentrations of c-ICAM-1 after BPT may reflect the upregulated expression of airway ICAM-1 during allergen-induced airway inflammation. We propose that c-ICAM-1 is a useful marker for allergic inflammation, particularly that of eosinophilic infiltration into the airway, an essential feature of asthma.