Four successive cases of human fasciolosis in Japan.

Fasciolosis is a food-borne parasitic disease, caused by the large liver fluke, Fasciola. Humans acquire infection by ingesting fresh or undercooked water plants, on which infective metacercaria encyst. In spite of the rarity of the disease in Japan, we encountered four successive fasciolosis patients within a short period, who were all living in the same area. The patients were 70-82 years old, three females and the husband of one of the female patients. They started complaining of non-specific symptoms, such as fever, general fatigue, appetite loss, and abdominal pain, almost at the same time. All patients showed prominent peripheral blood eosinophilia, and the medical imaging indicated multiple hepatic lesions. No parasite eggs or worms were detected in any of the patients. Diagnosis was made serologically and they were treated with praziquantel and/or triclabendazole. No cattle or sheep were farmed in the area, but the wild sika deer, Cervus nippon, inhabited adjacent to the residential area. The intermediate host snail, Austropeplea ollula, were found near the residence of the patients, and one of the collected snails was positive for F. hepatica/gigantica hybrid type rediae. Our report should alarm the medical professionals for this rare and unfamiliar parasitic disease.

Temporal effects of lascufloxacin on human gut and salivary microbiota: Analysis using next-generation sequencing method.

INTRODUCTION: Antimicrobial treatment disrupts human microbiota. The effects of lascufloxacin (LSFX), a new fluoroquinolone, on human microbiota remains unknown. Therefore, in this study, we aimed to evaluate the effects of LSFX administration on the gut and salivary microbiota of healthy participants and those with pneumonia. METHODS: LSFX (75 mg, once a day, orally) was administered to healthy adults (healthy group) and adult patients with pneumonia (pneumonia group), and fecal and saliva samples were collected at five time points (Days 0, 3, 7, 14, and 28). Using the collected samples, α- and ß-diversity indices, as well as bacterial composition of the gut microbiota and salivary microbiota were analyzed using next-generation sequencing. RESULTS: In the healthy group, α-diversity indices of the gut and salivary microbiota were reduced and the lowest values on Day 3. For the gut microbiota, the Chao1 index (richness) recovered on Day 28, whereas the Shannon index (evenness) did not. In the salivary microbiota, the Chao1 and Shannon indices did not recover within the 28 day period. The ß-diversity indices changed after LSFX administration and subsequently recovered on Day 28. After LSFX administration, the abundance of the Lachnospiraceae family decreased in the gut microbiota, and the abundance of Granulicatella, Streptococcus, Prevotella, Absconditabacteriales(SR1), and Saccharimonadales decreased in the salivary microbiota. In the pneumonia group, the α-diversity indices were lowest on Day 14 after LSFX administration. CONCLUSIONS: We elucidated that LSFX administration differentially affected the gut and salivary microbiota; however, the richness and beta diversity recovered within 28 days.

[Fatal invasive pneumococcal disease developed 14 years after allogeneic hematopoietic stem cell transplantation in a patient with myelodysplastic syndrome].

Invasive pneumococcal diseases (IPDs) after allogeneic hematopoietic stem cell transplantation have high fatality rates and often develop late after transplantation. The patient was a 58-year-old female. Fourteen years ago, she underwent bone marrow transplantation from a HLA-DR 1-antigen mismatched unrelated donor for myelodysplastic syndrome. She developed pneumonia, chronic graft-versus-host disease, and hypogammaglobulinemia. She received 23-valent pneumococcal capsular polysaccharide vaccine 11 and 6 years earlier. She was presented to our emergency room with fever. Her blood culture was positive for pneumococcus, and she was diagnosed with an IPD. The patient received antibiotic treatment but died on the third day of hospitalization. Because of its seriousness, pneumococcal infection should receive attention even 10 or more years after transplantation. Preventive approaches such as vaccination and early intervention at the time of diagnosis are important.

Three-day regimen of oseltamivir for post-exposure prophylaxis of influenza in hospital wards: a study protocol for a prospective, multi-center, single-arm trial.

BACKGROUND: In a previous retrospective observational study, a 3-day regimen of oseltamivir as post-exposure prophylaxis (PEP) for preventing transmission of influenza in wards was shown to be comparable to 7- to 10-day regimens provided index cases were immediately separated from close contacts. In order to confirm the efficacy of a 3-day regimen, we started to conduct a prospective, multi-center, single-arm trial. METHODS: This study is a prospective, multi-center, single-arm study designed by the Sectional Meeting of Clinical Study, Japan Infection Prevention and Control Conference for National and Public University Hospitals. Index patients with influenza are prescribed a neuraminidase inhibitor and are discharged immediately or transferred to isolation rooms. The close contacts are given oseltamivir as 75 mg capsules once daily for adults or 2 mg/kg (maximum of 75 mg) once daily for children for 3 days as PEP. All close contacts are monitored for development of influenza for 7 days after starting PEP. DISCUSSION: A 3-day regimen of oseltamivir as PEP has advantages over 7- to 10-day regimens in terms of costs, medication adherence and adverse effects. Trial registration The Institutional Review Board of Hokkaido University Hospital for Clinical Research, 015-0518, registered on November 11, 2016. UMIN Clinical Trials Registry, UMIN000024458, disclosed on October 31, 2016. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027881 . Japan Registry of Clinical Trials, jRCTs011180015, disclosed on March 14, 2019. https://jrct.niph.go.jp/latest-detail/jRCTs011180015.

Evaluation of infections in orthopedic patients using next-generation sequencing.

INTRODUCTION: Culture tests are used to diagnose infections, but there are various problems such as low sensitivity in detecting infections in orthopedic cases. To address this problem, next generation sequencing (NGS) analysis, which can comprehensively search for bacterial genes, is being applied clinically. In this study, we examined whether NGS analysis was useful in evaluating infections in orthopedic cases. METHODS: The participants were 23 patients suspected of having an infection between 2016 and 2017. Samples were collected from tissues suspected of being infected and were subjected to culture tests and NGS analysis, and the positive rates from the culture tests and from the NGS analysis were compared. We also attempted to determine cutoff value for the NGS analysis. RESULTS: A total of 20 cases were ultimately diagnosed as infections and 3 cases were diagnosed as non-infections. The sensitivity of the culture tests was 70%, and the sensitivity of the NGS analysis was 55%. When the NGS analysis was performed with the diversity index set to the cut-off value, the sensitivity was 75% for the Simpson index. In this study, the sensitivity was 90% when the analysis was performed using the NGS index, which is a combination of the diversity index and the OTUs (operational taxonomic units) value. CONCLUSION: NGS analysis using the NGS index showed excellent sensitivity and specificity compared to culture tests. NGS analysis is therefore a useful modality for assessing infections in orthopedic cases.

Peritoneal dialysis-associated peritonitis caused by Mycobacteroides massiliense: the first case and review of the literature.

BACKGROUND: Peritoneal dialysis (PD)-associated peritonitis caused by nontuberculous Mycobacterium is rare; however, the number of cases has increased over the past decades. Mycobacteroides massiliense is a subspecies of the Mycobacteroides abscessus complex. It has different clinical characteristics compared to the other subspecies of the complex. Previous case reports of PD-associated peritonitis caused by Mycobacteroides abscessus complex have not distinguished the subspecies in detail. CASE PRESENTATION: A 40-year-old man presented with an exit-site and tunnel infection refractory to antibiotic therapy. Peritonitis occurred after simultaneous catheter removal and reinsertion. The Mycobacteroides abscessus complex was detected in the culture of the dialysis effluent. Removal of the PD catheter combined with antibiotics, including macrolides, resulted in a good clinical course. Further analysis of multiplex PCR and the hsp65 gene sequence identified the bacterium as Mycobacteroides massiliense. CONCLUSIONS: The Mycobacteroides abscessus complex is classified into three subspecies; Mycobacteroides abscessus, Mycobacteroides massiliense, and Mycobacteroides bolletii. These have different characteristics, particularly antibiotic susceptibility. Therefore, clear identification of the subspecies of the Mycobacteroides abscessus complex is necessary for definitive treatment.

Properties of Achromobacter xylosoxidans highly resistant to aminoglycoside antibiotics.

We herein discovered a highly resistant clinical isolate of Pseudomonas aeruginosa with MICs to amikacin, gentamicin, and arbekacin of 128 µg/mL or higher in a drug sensitivity survey of 92 strains isolated from the specimens of Yoka hospital patients between January 2009 and October 2010, and Achromobacter xylosoxidans was separated from this P. aeruginosa isolate. The sensitivity of this bacterium to 29 antibiotics was investigated. The MICs of this A. xylosoxidans strain to 9 aminoglycoside antibiotics were: amikacin, gentamicin, arbekacin, streptomycin, kanamycin, neomycin, and spectinomycin, 1,024 µg/mL or ≥ 1,024 µg/mL; netilmicin, 512 µg/mL; and tobramycin, 256 µg/mL. This strain was also resistant to dibekacin. This aminoglycoside antibiotic resistant phenotype is very rare, and we are the first report the emergence of A. xylosoxidans with this characteristic.

γ-Tocotrienol reduces human airway smooth muscle cell proliferation and migration.

AIMS: Vitamin E is an antioxidant that occurs in 8 different forms (α, ß, γ, and δ tocopherol and tocotrienol). Clinical trials of tocopherol supplementation to assess the impact of antioxidant activity in asthma have yielded equivocal results. Tocotrienol exhibits greater antioxidant activity than tocopherol in several biological phenomena in vivo and in vitro. We tested the effect of tocotrienol on human airway smooth muscle (ASM) cell growth and migration, both of which mediate airway remodeling in asthma. MAIN METHODS: We measured platelet-derived growth factor-BB (PDGF-BB)-induced ASM cell proliferation and migration by colorimetric and Transwell migration assays in the presence and absence of γ-tocotrienol (an isoform of tocotrienol). KEY FINDINGS: PDGF-BB-induced ASM cell proliferation and migration were inhibited by γ-tocotrienol. This effect was associated with inhibition of RhoA activation, but it had no effect on p42/p44 mitogen-activated protein kinase (MAPK) or Akt1 activation. We confirmed that pharmacological inhibition of Rho kinase activity was sufficient to inhibit PDGF-BB-induced ASM cell proliferation and migration. SIGNIFICANCE: γ-Tocotrienol could impart therapeutic benefits for airway remodeling in asthma by inhibiting human ASM cell proliferation and migration.

Respiratory viruses and torque teno virus in adults with acute respiratory infections.

OBJECTIVE: To define the molecular epidemiology of respiratory viral infections in adult patients. METHODS: Nasal and throat swabs were collected from all adult patients with influenza-like illness (ILI), acute respiratory infection (ARI), or severe ARI (SARI) admitted to a tertiary hospital in Surakarta, Indonesia, between March 2010 and April 2011 and analyzed for 19 respiratory viruses and for torque teno virus (TTV) and human gyrovirus (HGyV). RESULTS: Respiratory viruses were detected in 61.3% of the subjects, most of whom had ARI (90.8%, OR = 11.39), were hospitalized (96.9%, OR = 22.31), had asthma exacerbation (90.9%, OR = 8.67), and/or had pneumonia (80%, OR = 4.0). Human rhinovirus (HRV) A43 predominated. Influenza A H3N2, human metapneumovirus (HMPV) subtypes A1 and A2, the influenza B virus, human adenovirus B, and human coronavirus OC43 were also detected. All respiratory viruses were detected in the transition month between the rainy and dry seasons. No mixed respiratory virus infection was found. Coinfections of the influenza A H3N2 virus with TTV, HMPV with TTV, HRV with TTV, and human parainfluenza virus-3 with TTV were found in 4.7, 2.8, 19.8, and 0.9% of the samples, respectively. CONCLUSIONS: This study highlights the need to perform routine detection of respiratory viruses in adults hospitalized with ARI, asthma exacerbation, and/or pneumonia.

PDZ-RhoGEF and LARG are essential for embryonic development and provide a link between thrombin and LPA receptors and Rho activation.

G protein-coupled receptors (GPCRs) linked to both members of the Gα12 family of heterotrimeric G proteins α subunits, Gα12 and Gα13, regulate the activation of Rho GTPases, thereby contributing to many key biological processes. Multiple Rho GEFs have been proposed to link Gα12/13 GPCRs to Rho activation, including PDZ-RhoGEF (PRG), leukemia-associated Rho GEF (LARG), p115-RhoGEF (p115), lymphoid blast crisis (Lbc), and Dbl. PRG, LARG, and p115 share the presence of a regulator of G protein signaling homology (RGS) domain. There is limited information on the biological roles of this RGS-containing family of RhoGEFs in vivo. p115-deficient mice are viable with some defects in the immune system and gastrointestinal motor dysfunctions, whereas in an initial study we showed that mice deficient for Larg are viable and resistant to salt-induced hypertension. Here, we generated knock-out mice for Prg and observed that these mice do not display any overt phenotype. However, deficiency in Prg and Larg leads to complex developmental defects and early embryonic lethality. Signaling from Gα11/q-linked GPCRs to Rho was not impaired in mouse embryonic fibroblasts defective in all three RGS-containing RhoGEFs. However, a combined lack of Prg, Larg, and p115 expression abolished signaling through Gα12/13 to Rho and thrombin-induced cell proliferation, directional migration, and nuclear signaling through JNK and p38. These findings provide evidence of an essential role for the RGS-containing RhoGEF family in signaling to Rho by Gα12/13-coupled GPCRs, which may likely play a critical role during embryonic development.

[A case of lung abscess due to Aspergillus viridinutans in a patient with aplastic anemia].

A 75-year-old woman with aplastic anemia was admitted to our university hospital because of a dry cough that had persisted for a month. Chest computed tomography showed a mass shadow with a central low attenuation area in the lower lobe of the left lung. Filamentous fungus resembling Aspergillus fumigatus was cultured from the specimens obtained by transthoracic needle aspiration biopsy and bronchoalveolar lavage. The initial diagnosis was a lung abscess due to A. fumigatus, although the patient did not respond well to antifungal agents. Subsequently, the filamentous fungus was identified as Aspergillus viridinutans by sequence analysis of the ß-tubulin gene, and the patient was successfully treated with combination therapy along with granulocyte colony-stimulating factor. The incidence of A. viridinutans infection is very rare. A. viridinutans is morphologically similar to A. fumigatus; however, the response to antifungal agents is generally worse than that observed in A. fumigatus infections. Therefore, the selection of agents and supplemental therapy is of vital importance in cases of A. viridinutans infection.

Difference in TMPRSS2 usage by Delta and Omicron variants of SARS-CoV-2: Implication for a sudden increase among children.

It has been postulated from a combination of evidence that a sudden increase in COVID-19 cases among pediatric patients after onset of the Omicron wave was attributed to a reduced requirement for TMPRSS2-mediated entry in pediatric airways with lower expression levels of TMPRSS2. Epidemic strains were isolated from the indigenous population in an area, and the levels of TMPRSS2 required for Delta and Omicron variants were assessed. As a result, Delta variants proliferated fully in cultures of TMPRSS2-positive Vero cells but not in TMPRSS2-negative Vero cell culture (350-fold, Delta vs 9.6-fold, Omicron). There was no obvious age-dependent selection of Omicron strains affected by the TMPRSS2 (9.6-fold, Adults vs. 12-fold, Children). A phylogenetic tree was generated and Blast searches (up to 100 references) for the spread of strains in the study area showed that each strain had almost identical homology (>99.5%) with foreign isolates, although indigenous strains had obvious differences from each other. This suggested that the differences had been present abroad for a long period. Therefore, the lower requirement for TMPRSS2 by Omicron strains might be applicable to epidemic strains globally. In conclusion, the property of TMPRSS2-independent cleavage makes Omicron proliferate with ease and allows epidemics among children with fewer TMPRSS2 on epithelial surfaces of the respiratory organs.

Rapid Multiplex RT-PCR for Influenza A and B by Genesoc®, a Microfluidic PCR System.

Background: Rapid antigen tests are widely used to diagnose influenza. However, despite their simplicity and short turnover time, the sensitivity of these tests is relatively low, and molecular tests with greater sensitivity are being sought. In this study, we developed and clinically evaluated a protocol for the rapid multiplex testing of influenza A and B, using a rapid real-time PCR system, GeneSoC®, that is based on microfluidic thermal cycling technology. Methods: The specificity of the developed assay was validated using cultured viral strains of influenza A/B, human metapneumovirus, and respiratory syncytial virus. Analytical sensitivity was evaluated using serially diluted RNA synthesized via in vitro transcription and nasopharyngeal swab samples collected from consecutive patients seeking medical attention for a combination of upper respiratory and general symptoms. Cross-validation of GeneSoC® based on comparisons with conventional real-time RT-PCR and rapid antigen tests was performed by parallel testing of influenza-positive clinical specimens. Results: The GeneSoC® assay detected the target sequences of influenza A and B at minimum concentrations of 38 and 65 copies/µL in reaction, respectively. For the analysis of clinical specimens, the positive, negative, and overall agreement between GeneSoC® RT-PCR and a conventional real-time RT-PCR was in all cases 100%, whereas for the comparison between GeneSoC® RT-PCR and the rapid antigen test, the agreements for positive, negative, and overall findings were 100%, 90.9%, and 95.7%, respectively. The mean time for completing GeneSoC® RT-PCR was 16 min 29 s (95% confidence interval, 16 min 18 s to 16 min 39 s). Conclusion: The microfluidic real-time PCR system, GeneSoC®, has an analytical performance comparable to that of conventional real-time RT-PCR with rapid turnover time, and represents a promising alternative to rapid antigen tests for diagnosing influenza A and B.

Diagnostic and prognostic impact of serum-soluble UL16-binding protein 2 in lung cancer patients.

UL16-binding protein 2 (ULBP2) is one of the ligands for NKG2D (NKG2DL). ULBP2 expression is induced in transformed cells and is recognized by immune effector cells via the activating NKG2D immunoreceptor. Soluble forms of NKG2DL have been reported in the serum of patients with several types of cancer. The present study investigated the diagnostic and prognostic significance of serum-soluble ULBP2 (sULBP2) in lung cancer patients. We used flow cytometry to evaluate the surface expression of NKG2DL by various lung cancer cells, while sULBP2 was measured using our original ELISA. In addition, the immunological effect of sULBP2 on peripheral blood mononuclear cells (PBMC) was examined by the (51) Cr release assay. We found that ULBP2 was highly expressed and that the sULBP2 level was elevated in supernatants of cultured non-small-cell lung cancer (NSCLC) cells as well as in the serum of NSCLC patients. ULBP2 levels were especially high in squamous cell carcinoma (SQ) patients. Clinical stage IIIB and IV NSCLC patients with a sULBP2 level ≥ 8.7 pg/mL showed significantly shorter survival than patients with sULBP2 <8.7 pg/mL. In multivariate analysis, a sULBP2 level ≥ 8.7 pg/mL (hazard ratio [HR], 2.13; P = 0.038) and clinical stage IV (HR, 2.65; P = 0.019) were independent determinants of a poor outcome. As a possible mechanism, we demonstrated that sULBP2 directly suppresses the cytolytic activity of PBMC. In conclusion, ULBP2 is the most significant NKG2DL for lung cancer, and sULBP2 is useful in the diagnosis of SQ and as a prognostic indicator for patients with advanced NSCLC.

Clinical characteristics and treatment outcomes of carbapenem-resistant Enterobacterales infections in Japan.

OBJECTIVES: The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan. METHODS: We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality. RESULTS: Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42-31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38-23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02-12.0], P = 0.046) were independent risk factors for 28-day mortality. CONCLUSION: The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections.

Pollen augments the influence of desert dust on symptoms of adult asthma patients.

BACKGROUND: East Asian desert dust storms that occur during mainly spring are called Asian dust storms (ADS). Our objective was to study the association of pollen and ADS with symptoms of adult asthma patients in Japan. METHODS: We designed a telephone survey to investigate the upper and lower respiratory, ocular, and skin symptoms of asthma patients during ADS in February, March, and December on 2009. Peak expiratory flow (PEF) was also measured from February to May. RESULTS: We surveyed 106 patients in February, 101 patients in March, and 103 patients in December. In February and March, Japanese cedar and/or cypress pollen was also in the atmosphere during ADS, but no pollen was identified during December survey. Worsening of upper or lower respiratory, ocular, or skin symptoms was noted by 20.8% of patients in February, 33.7% in March, and 16.5% in December. Worsening of symptoms was significantly more common in March than in February or December. Two patients needed emergency treatment for exacerbation during ADS in March, but no patient needed hospitalization in any period. There was no significant difference of the daily morning PEF/personal best PEF ratio between ADS days and control days. However, in patients with worsening of upper and/or lower respiratory tract symptoms, the daily morning PEF/personal best ratio was significantly associated with the atmospheric level of particulate matter, but not with levels of pollen or other air pollutants. CONCLUSIONS: Pollen augmented symptoms in adult asthma patients, but ADS on its own also were able to aggravate symptoms and pulmonary function.

Correlation between Asian dust storms and worsening asthma in Western Japan.

BACKGROUND: Severe wind storms during spring in East Asia, called Asian dust storms (ADS), have been assessed in the past for their effect on health in Asian countries. Our objective was to study the ADS association with asthma symptoms in adult patients in Japan. METHODS: We designed a telephone survey to assess ADS influence on upper and lower respiratory, ocular and cutaneous symptoms in 98 patients with adult asthma from April to May 2007. Peak expiratory flow (PEF) was also measured from February to May. RESULTS: Worsening lower respiratory symptoms were noted by 22 of 98 patients during ADS in April, when Japanese cedar pollen levels also increased. During ADS in May, however, Japanese cedar and cypress pollen levels were not elevated, 11 patients had worsening of lower respiratory symptoms. None required emergency treatment for the exacerbation. Lower respiratory symptoms worsening most were cough and sputum; this was more common in patients with allergic rhinitis or atopy than in those without (P < 0.05). Min%Max differed significantly at 88.7 ± 6.6% during dust dispersion period, defined as the ADS day plus the next 6 days, versus 92.0 ± 5.3% during the 7-day period before a dust storm. CONCLUSIONS: We found that ADS aggravated lower respiratory symptoms in adult patients with asthma, but this influence was mild.

Expression of functional leukotriene B4 receptors on human airway smooth muscle cells.

BACKGROUND: Leukotriene B4 (LTB4) increases in induced sputum and exhaled breath condensate in people with asthma. Furthermore, the T(H)2-type immune response and airway hyperresponsiveness induced by ovalbumin sensitization is markedly suppressed in LTB4 receptor (BLT) 1 null mice. These studies suggest that LTB4 may contribute to asthma pathophysiology. However, the direct effects of LTB4 on human airway smooth muscle (ASM) have not been studied. OBJECTIVES: We sought to determine the expression of LTB4 receptors on human ASM and its functional role in mediating responses of human ASM cells, and the effect of LTB4 on these cells. METHODS: Immunohistochemistry, RT-PCR, Western blotting, and flow cytometry were used to determine the expression of LTB4 receptors. To determine the effect of LTB4 on human ASM cells, cell proliferation was assessed by counting cells, and chemokinesis was assessed by gold particle phagokinesis assay. RESULTS: We confirmed expression of both BLT1 and BLT2 in human ASM cells in bronchial tissue and in cell culture. LTB4 markedly induced cyclin D1 expression, proliferation, and chemokinesis of human ASM cells. LTB4 also induced phosphorylation of both p42/p44 mitogen-activated protein kinase (MAPK) and downstream PI3 kinase effector, Akt1. However, we observed no induction of c-Jun N-terminal kinase or p38 MAPK. Notably, LTB4-induced migration and proliferation of ASM cells were inhibited by the BLT1 specific antagonist, U75302, and by inhibitors of p42/p44 MAPK phosphorylation (U1026), and PI3 kinase (LY294002). CONCLUSIONS: These observations are the first to suggest a role for a LTB4-BLT1 signaling axis in ASM responses that may contribute to the pathogenesis of airway remodeling in asthma.

[Peripheral T-cell lymphoma unspecified with remarkably extensive airspace consolidations and ground-glass opacities of bilateral lung fields].

A 53-year-old man had presented to a nearby hospital with fever, dyspnea and multiple lymphadenopathy. Chest X-ray film and computed tomography had shown expanded airspace consolidations with air broncograms and surrounding ground-glass opacities in bilateral lung fields. Because his respiratory status had gradually worsened, he was transferred to our hospital and placed on the ventilator. Bronchoalveolar lavage were performed, showing abnormal lymphocytes which indicated infiltration of malignant lymphoma. Furthermore, a biopsy of the left inguinal lymph node revealed T-cell lymphoma. We finally diagnosed his pulmonary lesions as involvement of peripheral T-cell lymphoma unspecified in consideration of immunohistochemical estimation. Pulmonary involvement of malignant lymphoma is thought to be relatively uncommon. Therefore, this is considered an extremely rare case showing extensively spreading airspace consolidations and surrounding ground-glass opacities of bilateral lung fields caused by the infiltration of malignant cells along with lymphoid tissues. Because these radiological findings may indicate a severe status of lymphoma, it is necessary to diagnose and treat them immediately. From this point of view, we report this case with useful information concerning differential radiological diagnosis.

[Acute bird-related hypersensitivity pneumonitis: radiological findings in a case in the early phase after onset].

A 71-year-old woman was admitted to our hospital four times because of high fever and dyspnea from September to November in 2007. We treated her with antibiotics on her first two admissions. HOwever, we suspected hypersensitivity pneumonitis on the third admission because she suffered from fever and dyspnea soon after she had been discharged and returned home. She recovered only with the oxygen therapy on the last two admissions. Computed tomography of the chest showed early phase localized consolidation but changed to ground-glass opacities spreading over the entire lung field later during her third and fourth admissions. Bronchial alveolar lavage showed increases in total cell count, lymphocytes and IgA of pigeon-dropping extracts' and budgerigar-dropping extracts. TBLB showed epithelioid cell granulomas without caseous necrosis and alveolar septal inflammation. Inhalation challenge test using freeze-dried pigeon-dropping extracts was positive, therefore we finally established a diagnosis of acute bird related hypersensitivity pneumonitis. This is apparently the first report of acute bird-related hypersensitivity pneumonitis showing localized consolidation initially and later changing to diffuse ground-glass opacities. These radiological observations are significant in considering the onset and the progression of this disease.