Search

Background: In critically ill patients, healthy vitamin C levels are important to avoid an imbalance in reactive oxygen species. To achieve this, oxidative stress levels in emergency patients need to be accurately measured in real-time. However, normally, reactive oxygen/nitrogen species are short-lived, rendering measurement difficult; moreover, measurement of relatively stable antioxidants and other oxidative stress markers in real-time is challenging. Therefore, we used electron-spin resonance spectrometry (ESR) to assess vitamin C levels, clarify their relationship with patients' severity, and establish more effective vitamin C therapy in critically ill patients., Methods: We studied 103 severely ill emergency patients and 15 healthy volunteers. Vitamin C radical (VCR/dimethyl sulfoxide [DMSO]) values were analyzed in arterial blood samples by ESR at admission and once daily thereafter during the acute recovery phase. Severity scores were calculated. The relationship between these scores and VCR/DMSO values and chronological changes in VCR/DMSO values were analyzed., Results: Serum VCR/DMSO values were significantly lower in critically ill patients than in healthy volunteers (0.264 ± 0.014 vs. 0.935 ± 0.052, p < 0.05), particularly in the severe trauma group and the cardiopulmonary arrest/post-cardiac arrest syndrome group. VCR/DMSO values and various severity scores did not correlate at admission; however, they correlated with SOFA scores from days 2-6. VCR/DMSO values remained low from the first measurement day through Day 6 of illness., Conclusions: Vitamin C levels were low at admission, remained low with conventional nutritional support, and did not correlate with the initial patient's severity; however, they correlated with patients' severity after admission. Some patients had normal vitamin C levels. Therefore, vitamin C levels should be measured in real-time and supplemented if they are below normal levels., Trial Registration: Retrospectively registered., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Corynebacterium ulcerans is a closely related bacterium to the diphtheria bacterium C. diphtheriae, and some C. ulcerans strains produce toxins that are similar to diphtheria toxin. C. ulcerans is widely distributed in the environment and is considered one of the most harmful pathogens to livestock and wildlife. Infection with C. ulcerans can cause respiratory or nonrespiratory symptoms in patients. Recently, the microorganism has been increasingly recognized as an emerging zoonotic agent of diphtheria-like illness in Japan. To clarify the overall clinical characteristics, treatment-related factors, and outcomes of C. ulcerans infection, we analyzed 34 cases of C. ulcerans that occurred in Japan during 2001-2020. During 2010-2020, the incidence rate of C. ulcerans infection increased markedly, and the overall mortality rate was 5.9%. It is recommended that adults be vaccinated with diphtheria toxoid vaccine to prevent the spread of this infection.

We report a case of pneumocystis pneumonia (PCP) that mimicked atypical pneumonia in a patient with human immunodeficiency virus (HIV) infection. A 44-year-old Japanese man with persistent fever and dyspnea for a month was diagnosed with atypical pneumonia because of bilateral ground-glass opacities on chest computed tomography (CT). Ground-glass opacities on chest CT diminished with three days treatment of azithromycin; however, his symptoms were persistent. Final diagnosis of HIV and PCP infection was eventually confirmed. Physicians should consider the possibility of PCP even when pulmonary manifestations resolve with azithromycin in patients with HIV infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Hashimoto et al.)

Subcutaneous sarcoidosis is the specific subset of cutaneous sarcoidosis frequently associated with systemic disease. However, the disease activity, severity, and prognosis have not yet been elucidated due to the limited number of reported cases. The purpose of this study was to identify the clinical, laboratory, and prognostic differences between subcutaneous sarcoidosis and other type of cutaneous sarcoidosis. All patients with sarcoidosis diagnosed histopathologically from 2000 to 2012 at our institution were enrolled. The clinical, laboratory, chest X-ray, and pulmonary function test results were retrospectively evaluated in the patients with cutaneous sarcoidosis. In the 130 patients with sarcoidosis, cutaneous sarcoidosis was diagnosed in 37 patients (28.4 %), and 9 (6.9 %) of these patients had subcutaneous sarcoidosis. The serum levels of soluble interleukin-2 receptor (sIL-2R) were significantly elevated in the group of patients with subcutaneous sarcoidosis in comparison to the patients with other types of cutaneous sarcoidosis, whereas there was no significant difference in the severity score between the two groups. Following a 2-year observation period, three patients were in remission, five patients demonstrated stable disease, and one patient had progressive disease. Subcutaneous sarcoidosis may be associated with the disease activity, although it was not found to be associated with the disease severity and it was not a predictive factor for the prognosis. Furthermore, the prevalence of subcutaneous sarcoidosis may be higher than that in previously reported series.

Relapsing polychondritis (RP) is a rare systemic disorder characterized by recurrent, widespread chondritis of the auricular, nasal, and tracheal cartilages. IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease characterized by the infiltration of IgG4-bearing plasma cells into systemic organs. Although 25% to 35% of patients with RP have a concurrent autoimmune disease, coexistence of RP and IgG4-RD is rare. We herein report a case of RP complicated by IgG4-RD. A 63-year-old man developed recurrent bilateral ear pain and swelling, recurrent blurred and decreased vision, and migratory multiple joint pain, sequentially within one year. Fourteen months after the first symptom, he experienced dry cough and dyspnea with exertion. A computed tomography (CT) scan detected interstitial pneumonia, swelling of bilateral submandibular glands, bilateral hilar and mediastinal lymphadenopathy, and several nodules in bilateral kidneys. His serum levels of IgG and IgG4 were elevated. The biopsy specimen of auricular cartilage showed infiltrations of inflammatory cells and fibrosis consistent with RP. The IgG4-positive cells were not observed in auricular cartilage. The patient met the diagnostic criteria of RP, including bilateral auricular chondritis, conjunctivitis, iritis and polyarthritis. The biopsy specimens of lung and kidney revealed the significant infiltrations of IgG4-positive plasma cells and fibrosis. We also diagnosed him as having IgG4-RD, affecting bilateral submandibular glands, hilar and mediastinal lymph nodes, lungs, and kidneys. Thus, RP preceded the onset of IgG4-RD. Corticosteroid therapy improved the symptoms and CT scan findings. In conclusion, RP and IgG4-RD do coexist; however, the pathogenesis of their coexistence is unknown.

We herein report a rare case of sarcoidosis presenting as bilateral vocal cord paralysis due to bilateral vagal nerve involvement. A 72-year-old woman with uveitis of the left eye complained of hoarseness and aspiration due to bilateral vocal cord paralysis. An endobronchial needle aspiration biopsy specimen of the mediastinal lymph nodes showed non-caseating epithelioid cell granuloma. Total protein and cell concentrations in the cerebrospinal fluid were increased. We diagnosed her to have sarcoidosis with bilateral vagal nerve involvement. Corticosteroid therapy improved her symptoms of hoarseness and aspiration. Sarcoidosis should therefore be taken into consideration as a potential cause of bilateral vocal cord paralysis.

Dating back nearly 35 years ago to the Witschi hypothesis, epithelial cell dysfunction and abnormal wound healing have reemerged as central concepts in the pathophysiology of idiopathic pulmonary fibrosis (IPF) in adults and in interstitial lung disease in children. Alveolar type 2 (AT2) cells represent a metabolically active compartment in the distal air spaces responsible for pulmonary surfactant biosynthesis and function as a progenitor population required for maintenance of alveolar integrity. Rare mutations in surfactant system components have provided new clues to understanding broader questions regarding the role of AT2 cell dysfunction in the pathophysiology of fibrotic lung diseases. Drawing on data generated from a variety of model systems expressing disease-related surfactant component mutations [surfactant proteins A and C (SP-A and SP-C); the lipid transporter ABCA3], this review will examine the concept of epithelial dysfunction in fibrotic lung disease, provide an update on AT2 cell and surfactant biology, summarize cellular responses to mutant surfactant components [including endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and intrinsic apoptosis], and examine quality control pathways (unfolded protein response, the ubiquitin-proteasome system, macroautophagy) that can be utilized to restore AT2 homeostasis. This integrated response and its derangement will be placed in the context of cell stress and quality control signatures found in patients with familial or sporadic IPF as well as non-surfactant-related AT2 cell dysfunction syndromes associated with a fibrotic lung phenotype. Finally, the need for targeted therapeutic strategies for pulmonary fibrosis that address epithelial ER stress, its downstream signaling, and cell quality control are discussed., (Copyright © 2015 the American Physiological Society.)

Here, we report a case of pneumonia possibly caused by the aspiration of runoff water containing Chromobacterium haemolyticum. A 69-year-old man became intoxicated with alcohol, fell into a ditch, and lost consciousness after suffering a blow to the head. The lower half of his body was completely paralyzed because of damage to his spinal cord, and he aspirated runoff water from the ditch. Chest computed tomography scans revealed consolidation in the right upper lobe and bilateral lower lobes. A sputum culture detected gram-negative bacteria that was identified as C. haemolyticum. Antibacterial chemotherapy was initiated, and the clinical course was favorable. To the best of our knowledge, this is the first report of C. haemolyticum pneumonia in the literature.

Exophiala dermatitidis pneumonia is extremely rare. Here we report a case of E. dermatitidis pneumonia successfully treated with long-term itraconazole therapy. A 63-year-old woman without a remarkable medical history developed a dry and chest pain. Chest radiographs revealed consolidation in the middle lobe of the lung. Cytologic examination by bronchoscopy showed filamentous fungi and E. dermatitidis was detected in the bronchoalveolar lavage fluid. After 5 months of itraconazole therapy, her symptoms improved and the area of consolidation diminished. Two weeks after discontinuing the itraconazole therapy, the area of consolidation reappeared. Itraconazole therapy was restarted and continued for 7 months. The abnormal shadow observed on the chest X-ray gradually diminished. Over a 27-month follow-up with periodic examination, there was no relapse and the patient had a favorable clinical course., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We report an unusual case of cardiac sarcoidosis demonstrated by interventricular septal thickening. A 64-year-old woman was diagnosed with sarcoidosis involving the lungs, eyes, and skin. Three years later, renal dysfunction was detected during a periodic examination and a renal biopsy revealed non-caseating granulomas. Electrocardiogram results were normal, but an echocardiogram revealed thickening of the interventricular septum. Abnormal accumulation of gallium-67 and a perfusion defect in tecnetium-99-methoxyisobutylisonitrile scintigrams occurred in the interventricular septum. Magnetic resonance images showed T2-high intensity in the lesion. We considered the thickening to represent cardiac involvement of sarcoidosis. Oral prednisolone therapy diminished the interventricular septal thickening.

Background: Previous studies suggest that dendritic cells and macrophages play an important role in inflammation of eosinophilic pneumonia. The mechanism of dendritic cell and macrophage accumulation into the lung, however, is unknown. Here, we hypothesized that CCR7 ligands, CCL19 and CCL21, contribute to the accumulation of dendritic cells and alveolar macrophages in the inflamed lung of patients with eosinophilic pneumonia., Methods: Concentrations of the CCR7 ligands as well as CCL16, CCL17 and CCL22 in the bronchoalveolar lavage fluid of 53 patients with eosinophilic pneumonia, 29 patients with sarcoidosis, 18 patients with idiopathic pulmonary fibrosis and 12 healthy volunteers were measured by enzyme-linked immunosorbent assay. Cell sources of CCR7 ligands and CCR7-expressing cells in the bronchoalveolar lavage fluid were evaluated by immunocytochemistry., Results: CCL19 and CCL21 levels in the bronchoalveolar lavage fluid were significantly higher in patients with eosinophilic pneumonia than in controls. Levels of CCL19, but not CCL21, were statistically correlated with the levels of CCL16, CCL17 and CCL22 in patients with eosinophilic pneumonia. Immunocytochemistry revealed CCL19 expression in dendritic cells, macrophages and T-lymphocytes harvested from patients with eosinophilic pneumonia, and CCR7 expression in dendritic cells and macrophages. Levels of CCL19, but not CCL21, were significantly decreased after remission in patients with eosinophilic pneumonia. After provocation tests, CCL19 levels were elevated in all patients with eosinophilic pneumonia., Conclusions: These findings indicate that CCL19 rather than CCL21 may contribute to the accumulation of dendritic cells and macrophages in the inflamed lungs of patients with eosinophilic pneumonia., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Pulmonary fibrosis is a manifestation of microscopic polyangitis (MPA), and often precedes the detection of MPA. The prevalence and sequence of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) and MPA in patients initially diagnosed with idiopathic pulmonary fibrosis (IPF) have not been precisely elucidated., Methods: We enrolled 61 consecutive patients with IPF and measured the MPO-ANCA titers at initial presentation and during the follow-up period. Clinical, radiologic and histologic features of MPO-ANCA-positive cases were examined., Results: Of 61 patients, 3 (4.9%) had positive MPO-ANCA titers at the initial presentation of IPF. During the disease course, MPO-ANCA-positive conversion occurred in 6 patients and the prevalence of ANCA increased to 14.8%. Among the nine patients positive for MPO-ANCA, two patients developed MPA during follow-up. Histologic features of MPO-ANCA-positive pulmonary fibrosis were compatible with the usual interstitial pneumonia pattern in which alveolar hemorrhage and capillaritis were not observed. The patients with MPO-ANCA-positive conversion showed increased percentages of bronchoalveolar lavage eosinophils and more frequent complication of pulmonary emphysema compared to those with MPO-ANCA-negative IPF., Conclusions: The findings of the present study demonstrated that patients with an initial diagnosis of IPF occasionally acquire MPO-ANCA, which develops to MPA during the disease course of IPF. The presence of pulmonary eosinophilia and low attenuation areas on computed tomography scans might be predictive of MPO-ANCA positive conversion., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We herein report a case of hard metal lung disease that was successfully treated with inhaled corticosteroids. A 46-year-old man was admitted to our hospital due to coughing and an abnormal shadow on a chest radiograph. He had worked as a hard metal tool sharpener for five years. Chest computed tomography scans showed centrilobular micronodules and areas of ground-glass opacity in the bilateral lung fields. Video-associated lung biopsy specimens revealed bronchocentric interstitial pneumonia and cellular bronchiolitis. A high-energy dispersion X-ray microanalysis detected tungsten. The patient was diagnosed with hard metal lung disease. Inhaled corticosteroid therapy (800 μg of ciclesonide hydrofluoroalkane daily) resolved the patient's symptoms, elevated KL-6 level, abnormal areas of chest opacity and obstructive, restrictive and diffusion impairments.

Primary malignant melanoma of the trachea is extremely rare. We report here the first case of primary tracheal malignant melanoma in the asymptomatic stage. Incidentally, this 73-year-old man was found to have a flat tumor at the upper trachea on chest computed tomography scans. The tumor was surgically resected with end-to-end anastomosis and was diagnosed to be primary malignant melanoma of the trachea. Four months after the surgical resection, cervical lymph node metastasis was found. Despite the resection of metastatic lymph nodes and six courses of chemotherapy, he died of cachexia approximately two years after the discovery of the tracheal tumor.

Background and Objective: Osteopontin is a key cytokine involved in pro-inflammatory T helper type 1 (Th1)-associated immune responses, which has recently been implicated in allergic diseases. We investigated the pathogenic role of osteopontin in eosinophilic pneumonia., Methods: The concentrations of osteopontin and Th1- or Th2-associated cytokines were measured in BAL fluid (BALF) from 41 patients with eosinophilic pneumonia, including those with acute (AEP, n = 12), chronic (CEP, n = 16), or drug-induced eosinophilic pneumonia (DEP, n = 13). The results were compared with those from patients with other interstitial lung diseases. Immunocytochemistry and double immunofluorescence labelling were performed to determine the cellular source of osteopontin., Results: Osteopontin was significantly elevated in BALF from patients with eosinophilic pneumonia as compared with BALF from patients with drug-induced interstitial pneumonia, hypersensitivity pneumonitis, idiopathic interstitial pneumonia, or sarcoidosis, and also compared with BALF from healthy volunteers. Osteopontin concentrations elevated at the time of exacerbation decreased during clinical improvement, either spontaneously or as a result of corticosteroid therapy. Elevated concentrations of CXCL10, CCL17 and IL-10 were also detected in BALF from patients with eosinophilic pneumonia. Osteopontin concentrations in BALF of AEP patients were correlated with IL-5, as well as IL-10, CCL11, CCL17 and CXCL10 concentrations. In AEP and DEP patients, serum osteopontin concentrations were also elevated. Double immunofluorescence labelling showed that in patients with eosinophilic pneumonia, osteopontin was expressed in lung eosinophils., Conclusions: Osteopontin is likely to contribute to the development of inflammation in patients with eosinophilic pneumonia., (© 2010 The Authors. Respirology © 2010 Asian Pacific Society of Respirology.)

A 58-year-old male was admitted to our hospital because of periungual nailfold an erythema and erythematous rash on the dorsal joints of his hands and feet, but no muscle weakness. He was thus diagnosed to have amyopathic dermatomyositis. He had moderate hypoxemia and his chest computed tomography scans demonstrated bilateral ground-glass opacities, implicating complication with interstitial pneumonia. Therapy was initiated with pulsed methylprednisolone followed by high-dose corticosteroids, pulsed cyclophosphamide, and cyclosporine. The skin manifestations improved; however, the pulmonary infiltrates and hypoxemia deteriorated during the 2-month period of the treatment. The treatment was switched from cyclosporine to tacrolimus because of an inadequate clinical response to the therapy, and this resulted in the resolution of interstitial pneumonia. This case indicates that tacrolimus administration should be considered for patients with this life-threatening disorder when it is judged to be refractory to cyclosporine.

A 68-year-old woman presenting dyspnea on exertion was admitted. Hypoxemia and a considerably elevated level of serum KL-6 were noted. Chest high-resolution computed tomography (HRCT) scans demonstrated panlobular ground-glass opacities with a mosaic distribution and hilar and mediastinal lymphadenopathy. Bronchoalveolar lavage revealed an increased percentage of lymphocytes and an elevated CD4/CD8 ratio, implicating a diagnosis of sarcoidosis. However, as we could not exclude other diffuse lung diseases because of unusual HRCT pattern in sarcoidosis, video-assisted thoracoscopic lung biopsy was performed. The histology of epithelioid cell granulomas in the specimens of the lung and the lymph nodes confirmed a diagnosis of sarcoidosis. The lung specimens corresponding to areas of increased opacity demonstrated diffuse alveolitis with minimal fibrosis between individual granulomas. Immunohistochemistry for KL-6 provided positive results on alveolar lining cells in areas of alveolitis but not on granulomas. After steroid treatment, the ground-glass opacities disappeared and the serum KL-6 level normalized. We discuss this rare case of pulmonary sarcoidosis presenting panlobular ground-glass opacities with mosaic distribution.

Background: Eosinophilic pneumonia is characterized by the prominent accumulation of eosinophils and lymphocytes in the lung parenchyma. Liver-expressed chemokine (LEC)/CC chemokine ligand 16 (CCL16) is a novel functional ligand for H4 which is expressed on eosinophils and also an affinity ligand for CCR1, CCR2, CCR5 and CCR8 which are expressed on T lymphocytes and monocytes. The purpose of this study is to clarify the role of LEC/CCL16 in eosinophilic pneumonia., Methods: The LEC/CCL16 level was measured using an enzyme-linked immunosorbent assay in the bronchoalveolar lavage fluid (BALF) of 33 patients with eosinophilic pneumonia, 26 patients with sarcoidosis and 10 healthy volunteers. The cell sources of LEC/CCL16 in BALF were evaluated by immunocytochemistry., Results: The LEC/CCL16 levels in BALF from patients with eosinophilic pneumonia were significantly higher than those from patients with sarcoidosis and healthy volunteers. The BALF LEC/CCL16 levels correlated with the numbers of BALF eosinophils and lymphocytes, respectively. The BALF LEC/CCL16 levels were significantly decreased after remission in eosinophilic pneumonia. In immunocytochemistry, the LEC/CCL16 expression was clearly observed in CD1a-positive dendritic cells as well as in CD68-positive macrophages harvested from patients with eosinophilic pneumonia, but not from the controls., Conclusions: These results suggest that LEC/CCL16 produced by dendritic cells as well as by alveolar macrophages contributes to the accumulation of eosinophils and lymphocytes into the inflamed lungs of patients with eosinophilic pneumonia., (Copyright 2009 S. Karger AG, Basel.)

A 47-year-old female was diagnosed to have pulmonary, ocular, and nodular-type muscular sarcoidosis. Seven years later, nodules developed in all limb muscles. She received minocycline 200 mg daily, which resulted in an obvious reduction of the muscular sarcoidosis with a significant decrease in the serum angiotensin-converting enzyme level. Nine months later, the minocycline was discontinued, thus resulting in a rapid recurrence of the disease. The immediate readministration of minocycline again resulted in a prompt improvement. We detected Propionibacterium acnes within the granulomas in the affected muscle by an immunohistochemistry. More interestingly, we found a decrease in the circulating levels of interleukin-12 p40 and interferon-inducible protein-10 during the minocycline therapy. The minocycline therapy may be effective for sarcoidosis and the fact that the disease rapidly relapsed after discontinuation of the minocycline administration suggests that the mechanism of action in this case may be immunomodulating but not antimicrobial effect.

We tried to determine whether high-resolution computed tomography (HRCT) patterns correlate with the immunopathogenetic findings and whether they could provide helpful information for predicting the outcomes in non-neoplastic drug-induced pneumonitis. The HRCT images were classified as most suggestive of pneumonitis, diffuse alveolar damage (DAD), non-specific interstitial pneumonia, organizing pneumonia (OP), hypersensitivity pneumonitis, and acute eosinophilic pneumonia (AEP) in 34 patients with non-neoplastic drug-induced pneumonitis. The patients were analyzed for the bronchoalveolar lavage (BAL) cell findings and for the circulating levels of interferon-inducible protein 10 (IP-10) and macrophage-derived chemokine (MDC), which were measured by an enzyme-linked immunosorbent assay. The cumulative dose of corticosteroids received by the patients and the day when they required supplemental oxygen were calculated as outcome markers. There were no differences in the circulating chemokine levels and the BAL cell profiles except for the eosinophil percentages among the HRCT patterns. Most of the cases with pulmonary eosinophilia belonged to the OP and AEP groups, and the circulating MDC levels correlated with BAL eosinophil percentages. We could not find any relationship between the BAL cell profiles or the chemokine levels and the outcome markers. In contrast, the HRCT patterns rather predicted the outcomes because larger cumulative dose of steroids and longer oxygen supply were required for the patients in the DAD and OP groups. In contrast, all patients with AEP recovered without steroid administration. The present study suggests that HRCT does not predict cellular pathophysiology but it may predict the corticosteroid use in non-neoplastic drug-induced pneumonitis.

Background: In sarcoidosis, the T helper type 1 (Th1) response tends to predominate at affected disease sites; however, whether Th1/Th2 polarization occurs in the peripheral circulation is unknown., Methods: Fifty-two patients with sarcoidosis and 21 healthy volunteers were investigated. The concentrations of interferon-inducible protein 10 (IP-10)/CXCL10 and thymus- and activation-regulated chemokine (TARC)/CCL17 in the serum, bronchoalveolar lavage fluid (BALF) and culture supernatant were measured by an enzyme-linked immunosorbent assay. The circulating CXCR3+ CD4+ T cells and CCR4+ CD4+ T cells were assessed by flow cytometry., Results: The CXCR3- or CCR4-positive ratios among CD4+ T cells were both higher in sarcoidosis than in healthy volunteers. The serum levels of both IP-10 and TARC of the patients with sarcoidosis were significantly higher than those of the healthy volunteers. In patients with sarcoidosis, a larger amount of IP-10 was generated by the BALF cells, whereas IP-10 production by peripheral blood mononuclear cells did not increase in comparison to the control subjects. The TARC levels produced by peripheral blood mononuclear cells of sarcoidosis patients were significantly higher than those of the controls, while no difference existed between the 2 groups regarding TARC production by BALF cells., Conclusion: IP-10 is mainly produced at the lung and TARC in the peripheral circulation in sarcoidosis patients. Both IP-10 and TARC cooperatively play a role in the pathogenesis of sarcoidosis.

A 37-year-old woman was admitted to our hospital because of acute respiratory distress. Two weeks previously, amoxapine (75 mg/day) had been administered for the first time. Ten days later she developed a high fever, severe hypoxaemia and pulmonary infiltrates on chest CT, including patchy areas of ground-glass opacity, thickening of the interlobular septae and bronchial walls and pleural effusions. BAL showed a predominance of neutrophils, lymphocytes and erythrocytes but not eosinophils. Amoxapine was stopped, resulting in complete resolution of the pulmonary infiltrates. When the patient was re-exposed to amoxapine (52.5 mg total dose), high fever, reduced SaO(2) and pulmonary infiltrates reappeared. We concluded that acute respiratory distress may be associated with amoxapine treatment.

A 36-year-old man was transferred to the hospital for further evaluation of pulmonary infiltration. A diagnosis of acute eosinophilic pneumonia (AEP) was confirmed by clinical symptoms, bronchoalveolar lavage, and computed tomography findings. Skin tests with fungal antigens were performed by intradermal injection. Both the Arthus (8 h) and delay (24 h)-type skin tests were positive for only Candida albicans. A lymphocyte-stimulating test was also positive for C. albicans. The etiology of the AEP was confirmed by a C. albicans inhalation provocation test. In addition, peripheral blood mononuclear cells obtained from the patient produced Interleukin-5 following C. albicans stimulation. This is the first report of C. albicans as a probable cause of AEP. Evaluation of allergy to C. albicans should be performed in AEP before diagnosing the cause as idiopathic.

Background: The presentation of acute eosinophilic pneumonia (AEP) closely resembles that of acute lung injury (ALI)/ARDS, including its idiopathic form, acute interstitial pneumonia (AIP). AEP usually lacks peripheral eosinophilia at the acute phase; therefore, the establishment of serum biomarkers for AEP would be clinically useful., Methods: We measured the levels of thymus- and activation-regulated chemokine (TARC)/CCL17, eotaxin/CCL11, KL-6, and surfactant protein-D (SP-D) in serum for patients with acute parenchymal lung diseases including AEP (n = 17), AIP (n = 13), pneumonia-associated ALI/ARDS (n = 12), and alveolar hemorrhage (n = 7). To evaluate diagnostic ability, each marker was estimated by measuring the area under the receiver operating characteristic curve (AUC)., Results: Serum TARC/CCL17 levels of AEP patients were much higher than those of patients in other disease groups. More importantly, high circulating TARC/CCL17 levels were observed in AEP even at acute phase when peripheral eosinophilia was absent. TARC/CCL17 showed the largest AUC, and the TARC/CCL17 levels with cutoff points from 6,259 to 7,039 pg/mL discriminated AEP from other syndromes with sensitivity and specificity of 100%. The KL-6 level was low in most patients with AEP, and the sensitivity was 81.6% in cutoff with 100% specificity. The AUC for eotaxin/CCL11 and SP-D was small, with values of 0.73 (95% confidence interval [CI], 0.60 to 0.86) and 0.53 (95% CI, 0.31 to 0.64), respectively., Conclusions: This study indicates that the measurement of circulating TARC/CCL17 and KL-6 is useful for discriminating AEP from other causes of ALI.

Diagnosis of drug-induced pneumonia, which represents pulmonary toxicity caused by certain drugs, is difficult, as a large number of different drugs can elicit various immune-mediated diseases with distinct pathomechanisms. The drug-induced lymphocyte stimulation test (DLST) is widely used for diagnosing drug-induced pneumonia in Japan. Recent reports, however, indicate that DLST is not reliable for diagnosis of drug-induced pneumonia. To diagnose drug-induced pneumonia, a provocation test with the suspected drug is the most reliable method of assessing the relationship between the drug and pneumonia. We examined the correlation between the DLST and the provocation test in 6 cases of suspected drug-induced pneumonia. DLST was performed in all of the patients. The causes of pneumonia in all patients were confirmed by a provocation test. The DLST was positive in 3 of 6 cases of suspected drug-induced pneumonia, but the suspected drugs were ruled out by the provocation test. If we had relied solely on the DLST, these 3 cases would have been labeled as false allergy. The results of the DLST did not coincide with the results of the provocation test in any of the cases. Our results suggest that the DLST is not useful for the diagnosis of drug-induced pneumonia. Following provocation with the causative drug, reappearance of pulmonary infiltration was not observed in any of the cases. These findings indicate that a carefully performed provocation test is the safe and most reliable method.

We report the first case of pulmonary Corynebacterium ulcerans infection mimicking Churg-Strauss syndrome (CSS). Productive cough, fever, general fatigue, and weight loss developed in a 50-year-old man. Laboratory data revealed prominent eosinophilia and elevated serum IgE. On chest images, multiple nodules and cavities were predominantly detected in the right lung. Histopathologic examination showed necrotizing granulomas and vasculitis with massive eosinophilic infiltration identical to the findings seen in CSS; however, clusters of Gram-positive, coryneform rods were observed in the alveolar spaces. A toxigenic strain of C ulcerans was isolated from lung tissue. The patient was treated with antibiotics, and a favorable clinical course ensued.

Amyopathic dermatomyositis (ADM) is occasionally complicated by rapidly progressive interstitial pneumonia (RPIP), and in such cases, diffuse alveolar damage (DAD) is usually diagnosed at autopsy. Here, we present three patients with RPIP accompanied by ADM in whom lung disease was assessed at an early stage. High-resolution computed tomography (HRCT) carried out before the onset of dyspnoea revealed uniformly subpleural reticular opacity with faint ground-glass attenuation. At that stage, surgical lung biopsies from two patients showed histological patterns typical of cellular nonspecific interstitial pneumonia (NSIP). Despite pulse methylprednisolone and subsequent high-dose oral administration of prednisolone, lung disease progressed in all patients, with extensive areas of ground-glass opacity and consolidation observed in HRCT scans. DAD was confirmed histologically in one case. Additional administration of cyclosporine, pulse cyclophosphamide or high-dose intravenous administration of immunoglobulin rescued all patients. Our data suggest that ADM-associated interstitial pneumonia takes an aggressive course even when the radiological and histological features are consistent with NSIP. Aggressive combination therapy with high-dose steroids and immunosuppressive agents is required as early as possible for patients with this life-threatening disorder.

Backgrounds: CD26, a multifunctional T cell surface glycoprotein, is a type II transmembrane protein containing only six amino acid residues in its cytoplasmic region. In addition to its membrane form, CD26 exists in plasma in a soluble form (sCD26), which is thought to be the extracellular domain of the molecule cleaved from the cell surface. Recent studies indicated CD26 have an important role in the pathogenesis of asthma, known as Th2 like disease. The function of CD26 in the esosinophlic lung disease is not well understood., Methods: Serum sCD26 was determined by enzyme-linked immunosorbent assay in patients with acute eosinophilic pneumonia, chronic eosinophilic pneumonia (CEP), and sarcoidosis, and in healthy volunteers, to establish its value for discriminating between disease entities and as marker of disease activity., Results: Soluble CD26 was significantly reduced in CEP and was related to disease severity. In particular, sCD26 was inversely correlated with arterial oxygen tension in CEP., Conclusion: Serum levels of sCD26 might appear to be useful as a new marker of CEP disease activity.

Accurate genetic code translation is achieved by accumulation of hyper-specific chemical reactions. Transfer RNA (tRNA) acts as an adaptor molecule to link the genetic code (in messenger RNA) to a specific amino acid. tRNA itself has no ability to specifically bind with the cognate amino acid, while aminoacyltRNA synthetases (aaRSs) strictly recognize their cognate tRNA and amino acid, to synthesize a correctlypaired aminoacyl-tRNA, a substrate for ribosome. tRNA is initially transcribed by RNA polymerase as a precursor RNA with long extensions at the 5' and 3' terminus. Maturation of tRNA to a functional RNA requires processing of the extensional sequences and post-transcriptional chemical modifications, which ensures the specific aminoacylation of tRNA by the cognate aaRS. We have solved the crystal structure of the tRNA-maturating enzymes in a complex with tRNA (precursor) to especially elucidate the sophisticated mechanism of their highly specific chemical reactions. Our goal is to provide the animated crystallography or "movie" of the dynamic processes in the genetic code translation by capturing snapshots of the chemical reaction steps by X-ray crystallography.

We report an instructive case of minocycline-induced eosinophilic pneumonia confirmed by re-challenge test, in which a preceding lymphocyte-stimulation test indicated acetaminophen as the etiologic agent. A 55-year-old woman developed high fever and lung infiltrates with pulmonary eosinophilia after exposure to minocycline, acetaminophen, theophylline and procaterol. All of the medicines were discontinued, resulting in prompt improvement. The lymphocyte stimulation tests provided a positive result for acetaminophen, but not for the other medicines; however, a negative result was given by a re-challenge test with acetaminophen. In contrast, symptoms and hypoxemia reappeared when minocycline was re-administered. We would like to emphasize that lymphocyte stimulation test results need to be carefully interpreted for individual drugs.

Background: ADAM (a disintegrin and metalloprotease) family members, characterized by a metalloprotease and a disintegrin domain, are membrane-anchored glycoproteins involved in proteolysis and cell adhesion. ADAM8 might have an important role in allergic inflammation. It can cleave a variety of substrates and is a sheddase for VCAM-1 and CD23, the low-affinity IgE receptors., Methods: To evaluate the contribution of ADAM8 to the pathogenesis of eosinophilic pneumonia (EP), we measured the concentrations of soluble ADAM8 (sADAM8) and its substrates, soluble VCAM-1 (sVCAM-1) and soluble CD23 (sCD23), in bronchoalveolar lavage fluid from patients with smoking-induced acute eosinophilic pneumonia (AEP), chronic idiopathic eosinophilic pneumonia (CEP), and drug-induced eosinophilic pneumonia (drug-EP)., Results: The sADAM8 and sVCAM-1 concentrations were increased in AEP and CEP. The sCD23 concentration was elevated in AEP. In AEP, but not CEP, the sADAM8 concentration significantly correlated with those of both sVCAM and sCD23., Conclusion: The pathogenesis of AEP, CEP, and drug-EP was distinct with regard to ADAM8. Our results are the first to associate ADAM8 with eosinophilic responses and lung inflammation in humans.

A disintegrin and metalloprotease (ADAM) family members, characterized by a metalloprotease and a disintegrin domain, are membrane-anchored glycoproteins involved in proteolysis and cell adhesion. ADAM8 is specifically induced in the experimental murine asthmatic lung. To evaluate novel pathways involved in asthma pathogenesis, using ADAM8 transgenic mice (ATMS2) in a murine model of asthma. Massive cellular infiltrates in peribronchovascular and interstitial lesions were observed in control mice, while in ATMS2 mice there were only occasional. Vascular cell adhesion molecule (VCAM-1) is involved in specific eosinophil adhesions via alpha4beta1 integrin. VCAM-1 shedding was mediated by the ADAM8 metalloprotease. Endothelial cell shedding of VCAM-1 was increased in ATMS2-stimulated human umbilical endothelial cells. ADAM8-mediated shedding of VCAM-1 might be important for the suppression of experimental asthma. Our data suggest that ADAM8 is a useful therapeutic target.

A 32-year-old man was incidentally found to have abnormal shadows on a chest X-ray film and was admitted on May 2004. His chest images showed mediastinal and bilateral hilar lymphadenopathy. The serum level of angiotensin-converting enzyme was elevated. We also found non-caseating epithelioid cell granulomas in transbronchial lung biopsy specimens, and confirmed the diagnosis of sarcoidosis. We carried out bronchoalveolar lavage (BAL) for evaluation of disease activity of sarcoidosis. After BAL, he suffered high fever and polyarthralgia. Both ankles were extremely inflamed. We suspected infectious arthropathy caused by atypical pathogens and thus administered antibiotics, but they had no effect at all. Also, no findings suggesting collagen-vascular disorders, including rheumatoid arthritis, were detected. His symptoms improved after three-weeks of treatment with non-steroidal anti-inflammatory drugs. Thus, this case was diagnosed as having acute sarcoid polyarthritis. BAL may have influenced the onset of febrile arthritis in this patient This case indicates that sarcoidosis should be considered as a possible cause of acute febrile polyarthritis.

We examined the production of macrophage-derived chemokine (MDC/CCL22) and thymus- and activation-regulated chemokine (TARC/CCL17) by bronchoalveolar lavage fluid (BALF) cells in cigarette-smoke-associated acute eosinophilic pneumonia (CS-AEP). The CC Chemokine Receptor 4 (CCR4) ligand levels in BALF from patients with CS-AEP were considerably higher than those in healthy volunteers and correlated well with Th2 cytokine levels. Interleukin-4 enhanced CCR4 ligand production. MDC expression was observed in CD68-positive cells from patients with CS-AEP and in healthy control smokers. In contrast, TARC expression in CD68- or CD1a-positive cells was detected only in CS-AEP. An in vivo cigarette smoke challenge test induced increases in CCR4 ligands in the BALF and in the cultured supernatant of BALF adherent cells. These results suggest that alveolar macrophages and dendritic cells contribute to the pathogenesis of CS-AEP by generating CCR4 ligands, probably in response to cigarette smoke.

Thymus- and activation-regulated chemokine (TARC/CCL17) is a lymphocyte-directed CC chemokine, which plays a role in the recruitment of CC chemokine receptor-4 positive T helper 2 (Th2) cells. In this study, we measured concentrations of TARC and Th2 cell-derived cytokines in bronchoalveolar lavage (BAL) fluid, as well as TARC concentrations in serum from patients with eosinophilic pneumonia and other interstitial lung diseases. TARC was significantly elevated in BAL fluids from patients with eosinophilic pneumonia (median, 240 pg/ml), whereas TARC was undetectable (< 7 pg/ml) in most cases of hypersensitivity pneumonitis, sarcoidosis, and idiopathic pulmonary fibrosis, as well as in healthy control subjects. Also, when present, quantities were less than 20 pg/ml. Elevated concentrations of interleukin (IL)-4, IL-5, and IL-13 were also detected in BAL fluid from patients with eosinophilic pneumonia. Interestingly, TARC concentrations in BAL fluids were closely correlated with the concentrations of IL-5 and IL-13. A serial examination showed that elevated TARC in BAL fluid rapidly fell to below detectable limits preceding decreases in IL-5 concentration and eosinophil percentage. Our results, in concordance with previous studies, demonstrate the potential activity of TARC for recruiting Th2 cells to the lungs and suggest a significant role for TARC in the pathogenesis of eosinophilic pneumonia.