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For the purpose of a nationwide surveillance of the antimicrobial susceptibility of bacterial respiratory pathogens in patients in Japan, the Japanese Society of Chemotherapy conducted their second year survey, during the period from January to August, 2007. A total of 1178 strains were collected from clinical specimens obtained from adult patients with well-diagnosed respiratory tract infections. Susceptibility testing was evaluable for 1108 strains (226 Staphylococcus aureus, 257 Streptococcus pneumoniae, 6 Streptococcus pyogenes, 206 Haemophilus influenzae, 120 Moraxella catarrhalis, 122 Klebsiella pneumoniae, and 171 Pseudomonas aeruginosa). A total of 44 antibacterial agents, including 26 beta-lactams (four penicillins, three penicillins in combination with beta-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), three aminoglycosides, four macrolides (including ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standards Institute (CLSI). The incidence of methicillinresistant Staphylococcus aureus (MRSA) was high, at 59.7%, and the incidences of penicillin-intermediateresistant and -resistant Streptococcus pneumoniae (PISP and PRSP) were 30.4% and 5.1%, respectively. Among Haemophilus influenzae strains, 19.9% of them were found to be beta-lactamase-non-producing ampicillin (ABPC)-intermediately-resistant (BLNAI), 29.1% to be beta-lactamasenon-producing ABPC-resistant (BLNAR), and 6.7% to be beta-lactamase-producing ABPC-resistant (BLPAR) strains. Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae was not isolated. Two isolates (1.2%) of Pseudomonas aeruginosa were found to be metallo-beta-lactamase-producing strains, including one (0.6%) suspected multidrug-resistant strain showing resistance to imipenem, amikacin, and ciprofloxacin. These data will be a useful reference for future periodic surveillance studies and for investigations to control resistant infections as well. Continued surveillance is required to prevent the further spread of these antimicrobial resistances.

The Japanese Society of Chemotherapy (JSC) conducted the first nationwide surveillance of bacterial respiratory pathogens during the period from January to August 2006. With the cooperation of 32 medical institutions throughout Japan, a total of 924 strains belonging to seven clinically relevant bacterial species were collected from adult patients with well-diagnosed respiratory tract infections (RTIs). Antimicrobial susceptibility testing of the 887 evaluable strains (205 Staphylococcus aureus, 200 Streptococcus pneumoniae, 9 Streptococcus pyogenes, 165 Haemophilus influenzae, 91 Moraxella catarrhalis, 74 Klebsiella pneumoniae, and 143 Pseudomonas aeruginosa) to 42 antibacterial agents was conducted at the Central Laboratory of the Research Center for Anti-infective Drugs of the Kitasato Institute, according to recommendations issued by the Clinical and Laboratory Standards Institute (CLSI). The antibacterial agents employed were 25 beta-lactams, three aminoglycosides, four macrolides (including one azalide and one ketolide), one lincosamide, one tetracycline, two glycopeptides, five fluoroquinolones, and one oxazolidinone. The incidence of methicillin-resistant S. aureus (MRSA) was 63.4%, and the incidences of penicillin-intermediately resistant S. pneumoniae (PISP) and penicillin-resistant S. pneumoniae (PRSP) were 35.0% and 4.0%, respectively. Among H. influenzae, 21.2% of the strains were found to be beta-lactamase-nonproducing ampicillin (ABPC)-intermediately resistant (BLNAI), 29.1% to be beta-lactamase-nonproducing ABPC-resistant (BLNAR), and 4.8% to be beta-lactamaseproducing ABPC-resistant (BLPAR) strains. The incidence of extended-spectrum beta-lactamase-producing K. pneumoniae was 2.7% (2 of 74 strains). Three (2.1%) of the 143 P. aeruginosa strains were found to be metallo-beta-lactamaseproducing, including 1 (0.7%) multidrug-resistant strain. Through the nationwide surveillance, we obtained fundamental antimicrobial susceptibility data of clinically relevant bacterial pathogens in adult RTI to various antibacterial agents. These data will be a useful reference for future periodic surveillance studies, as well as for investigations to control antimicrobial-resistant pathogens.

Osteopontin (OPN) produced by alveolar macrophages functions as a fibrogenic cytokine in the development of bleomycin (BLM)-induced murine pulmonary fibrosis, and OPN mRNA is expressed on lung tissues from patients with idiopathic pulmonary fibrosis (IPF). The present study investigates plasma OPN levels in human interstitial pneumonia (IP) and their relationships with disease severity by analyzing the correlation between plasma OPN concentrations and pulmonary functions. The concentrations of OPN in plasma were measured in 17 patients with IP, in 9 with sarcoidosis and in 20 healthy controls using an antigen-capture enzyme-linked immunosorbent assay. The concentrations of OPN in plasma were significantly higher in IP patients than in those with sarcoidosis or in controls. Based on a Receiver Operating Characteristic curve analysis, cut-off points between 300 and 380ng/ml discriminated between IP and control subjects with 100% sensitivity and 100% specificity. In such case, the sensitivity for sarcoidosis decreased (55.5–33.3%) in cut-offs with 100% specificity. Plasma OPN levels inversely and closely correlated with arterial oxygen tension (PaO2) in patients with IP. Immunohistochemically, OPN was localized predominantly in macrophages and airway epithelium. These findings suggest that plasma OPN levels were found to be associated with the presence of IP, and that OPN play an important role in the development of IP.

Of the nonphysiological compounds in glucose-rich peritoneal dialysate, we investigated the cytotoxicity and synergistic cytotoxicity of acidity and glucose degradation products (GDPs) using human peritoneal mesothelial cells (HPMC). The effect of pH on cell viability was examined by adding 1N HCl to a phosphate-buffered solution (pHor = 5.5). We also examined the cytotoxic effects of various GDPs [glyoxal (GO), methylglyoxal (MGO), and 3-deoxyglucosone (3DG), alone or in combination] and pH (5.5 or 6.7). The cells were exposed to these solutions for 2 or 4 h. Cell viability was determined by 3,(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) assay. Although the MTT viability of HPMC was not decreased by GDP or acidity alone, the combination of acidity and GDP markedly decreased MTT viability, strongly suggesting the synergistic cytotoxicity of GDP and acidity.

Previous studies established that variable degrees and types of glycosylation can account for differences in the ability of CD44 to function as a receptor for hyaluronic acid. We have now used neuraminidase treatment to conclude that sialylation negatively regulates CD44 on the human monocytic cell line THP-1 and peripheral blood monocytes. Both of these cell types displayed increased receptor activity after overnight culture with LPS. Of particular interest, the sialidase inhibitor 2-deoxy-2,3-dehydro-N-acetylneuraminic acid completely blocked the LPS induced recognition of hyaluronic acid by THP-1 cells. Furthermore, acquisition of this characteristic paralleled induction of one type of sialidase activity. Monocytes may be capable of enzymaticly remodeling cell surface CD44, altering their ability to interact with the extracellular matrix.

Human neutrophils contain three isoforms of antimicrobial and cytotoxic peptides in the azurophil granules, which belong to a family of mammalian neutrophil peptides named defensins. Here we investigate the role of these peptides in diffuse panbronchiolitis (DPB). Defensins (human neutrophil peptide-1, -2 and -3) were measured by radioimmunoassay in bronchoalveolar lavage fluid (BALF) of 30 patients with DPB, 16 patients with idiopathic pulmonary fibrosis (IPF) and 15 healthy adults. The concentration of defensins was higher in BALF of patients with DPB than in patients with IPF and healthy subjects. DPB and IPF patients also had significantly higher plasma concentrations of defensins than controls. In patients with DPB, BALF concentration of defensins correlated significantly with neutrophil count or BALF concentration of interleukin (IL)-8. Immunohistochemistry of open-lung biopsy specimens from four DPB patients showed localization of defensins in neutrophils and mucinous exudate in the airways, and on the surface of bronchiolar epithelial cells. In vitro studies showed an enhanced extracellular release of defensins following stimulation of neutrophils with phorbol myristate acetate, N-formyl-methionyl-leucyl-phenyalamine, and human recombinant IL-8. Treatment of DPB with macrolides for 6 months significantly reduced neutrophil count and concentrations of defensins and IL-8 in BALF. Our results indicate accumulation of neutrophil-derived defensins in the airway in diffuse panbronchiolitis, and suggest that defensins may be a marker of neutrophil activity in this disease.

We report a case of Wegener's granulomatosis (WG), with neutrophil accumulation in bronchoalveolar lavage fluid (BALF). Peripheral blood neutrophilia was present but the anti-neutrophil cytoplasmic antibody (ANCA) was negative. The serum and BALF levels of neutrophil-related cytokines, including interleukin (IL)-8, granulocyte colony-stimulating factor (G-CSF) and IL-1 beta, were increased, particularly in BALF. Plasma and BALF levels of neutrophil elastase and defensins, which are released by neutrophils and are potentially toxic to cells, were also elevated. Our findings suggest that neutrophils and neutrophil-related cytokines may play an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody negative as well as anti-neutrophil cytoplasmic antibody positive Wegener's granulomatosis.

Giant cell carcinoma of the lung is a very rare primary malignant tumour and localised right upper-lobe pulmonary oedema is also unusual. We report a case of giant cell carcinoma, which invaded the left atrium through the left pulmonary vein and caused localised right upper-lobe pulmonary oedema.

Introduction Neisseria gonorrhoeae is one of the most important pathogens causing sexually transmitted infection. Resistant N. gonorrhoeae trains against several antimicrobials are increasing worldwide. In this study, the trends of antimicrobial susceptibilities among N. gonorrhoeae strains isolated from male patients with urethritis were investigated as the second Japanese national surveillance, which was conducted by a Japanese surveillance committee. Methods The targets were male patients older than 16 years with urethral discharge and symptoms of urethritis. Urethral discharge was collected from patients at 26 medical facilities from March 2012 to January 2013 and the antimicrobial susceptibility of strains were tested. Results From 151 patients (median age 32 years), 103 N. gonorrhoeae strains were tested for susceptibility to 20 antimicrobial agents. None was susceptible to penicillin G (MIC: ≤0.06 μg/mL). The prevalence of penicillinase producing N. gonorrhoeae or chromosomally mediated resistant N. gonorrhoeae was 1.9% or 20.8%, respectively. The susceptible rate for fluoroquinolone such as ciprofloxacin or levofloxacin was 20.3%. The susceptible rate for cefixime was 89.3%, that decreased from 98.8% at 2009. No ceftriaxone-resistant strains founded. The prevalence of less susceptible strain to ceftriaxone (MIC: 0.125 μg/mL) was 10.7%. No azithromycin high-resistant strain found and 5 strains (4.9%) had MIC ≥0.5 μg/mL. Among all strains, 83 strains (80.6%) were resistant to more than 2 kinds of antimicrobials and 42 strains (40.1%) was included to the criteria as multi-drug resistant N. gonorrhoeae . Conclusion The antimicrobial susceptibility of N. gonorrhoeae was not different between 2009 and 2012–2013, in Japan. Disclosure of interest statement Nothing to declare.

A 77-year-old woman was admitted to our hospital with congestive heart failure. A pansystolic murmur was audible at the apex. Echocardiography revealed a flail anterior leaflet of the mitral valve with massive mitral regurgitation, indicating a diagnosis of mitral regurgitation caused …

Of the non-physiological compounds in glucose-rich peritoneal dialysis fluid, we investigated the synergistic cytotoxicity of acidity and 3,4-Dideoxyglucosone-3-ene(3,4-DGE) under the existence of lactate using human peritoneal mesothelial cells (HPMC). The effect of pH on cell viability at various levels of pH (5.5, 6.7, 7.15), with or without lactate was examined by adding 1N-HCl to phosphate buffer solution. We also examined the cytotoxic effects of 3,4-DGE and pH (5.5, 6.7 or 7.15). Additionally, we compared the cytotoxic effects of 3,4-DGE and pH (5.5, 6.7 or 7.15) under existence of lactate (40 meq/L) or absence of lactate. The cells were exposed to these solutions for 2 or 4 h. Cell viability was determined by MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenylterazolium bromide) assay. 3,4-DGE or acidic solution alone had no significant effects on MTT viability under the absence of lactate. However, acidic solutions containing 3,4-DGE significantly decreased MTT viability under the existence of lactate. The MTT viability of HPMC was not decreased by 3,4-DGE or acidity alone under the absence of lactate. However, the combination of acidity and 3,4-DGE markedly decreased MTT viability under the existence of lactate, strongly suggesting the synergistic cytotoxicity of 3,4-DGE and acidity under the existence of lactate.

A 70-year-old man was admitted to our hospital with complaints of chest pain and exertional dyspnea. Chest radiography and computed tomography (CT) revealed right pleural effusion and pleural thickening on admission. The pleural fluid was bloody. Microbiological and cytologic examinations of the fluid were negative. The chest CT revealed progress of pleural thickening after hospitalization. A thoracoscopic pleural biopsy was performed, and the histological finding of the excised specimen was leiomyosarcoma. Because no organ of origin of the leiomyosarcoma, other than the pleura, was detected, this case was diagnosed as a primary pleural leiomyosarcoma. It is thought that leiomyosarcoma originating from the pleura is rare.

The purpose of this study was to evaluate the role of several eosinophil growth factors including interleukin (IL)-5, interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of interstitial lung disease with eosinophilia. IL-5, IL-3 and GM-CSF in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA) in patients with eosinophilic pneumonia (EP), bronchiolitis obliterans organizing pneumonia (BOOP), idiopathic pulmonary fibrosis (IPF), sarcoidosis and healthy volunteers. IL-5 in BALF was high only in patients with EP. IL-3 in BALF was undetectable in the majority of patients with these diseases. GM-CSF in BALF was detectable in 30-67% of each group of patients. In patients with BOOP and IPF, the number of eosinophils in BALF was higher in patients with detectable GM-CSF than in patients in whom GM-CSF was below the detection limit. Eosinophil cationic protein (ECP) was detected in all patients with EP and some with BOOP and IPF. There was a significant correlation between ECP levels and percentage or number of eosinophils in BALF. The results suggest the possibility that interleukin 5 in eosinophilic pneumonia, and granulocyte-macrophage colony-stimulating factor in bronchiolitis obliterans organizing pneumonia and idiopathic pulmonary fibrosis may play important roles in eosinophil recruitment in the lung. Activation of eosinophils in the lung is likely to be induced by both interleukin 5 and granulocyte-macrophage colony-stimulating factor.

CYFRA 21-1 and ProGRP have recently been established as new tumor markers for lung cancer. However, there are few reports evaluating concentrations in their bronchoalveolar lavage (BAL) fluid. In this study, we examined 81 patients with benign lung disease. The mean values of CYFRA 21-1 in the BAL fluid of each lung disease were as follows: bronchiolitis obliterans organizing pneumonia (BOOP), 3.9 +/- 2.1 ng/ml (positive rate 50%); collagen vascular disease associated interstitial pneumonia (CVD-IP), 10.7 +/- 15.7 ng/ml (positive rate 50%); diffuse panbronchiolitis (DPB), 4.2 +/- 6.4 ng/ml (positive rate 29%); idiopathic pulmonary fibrosis (IPF), 1.5 +/- 2.1 ng/ml (positive rate 17%); pulmonary infiltration with eosinophilia, 6.3 +/- 7.1 ng/ml (positive rate 44%); sarcoidosis, 4.6 +/- 6.2 ng/ml (positive rate 27%); and healthy volunteer (HV), 0.6 +/- 0.6 ng/ml; and total, 4.4 +/- 5.6 ng/ml (positive rate 32%). The mean values of ProGRP in the BAL fluid were as follows: DPB, 5.0 +/- 7.6 pg/ml (positive rate 0%); IPF, 6.4 +/- 10.6 pg/ml (positive rate 0%); HV, 12.4 +/- 8.3 pg/ml; and total, 5.6 +/- 8.7 pg/ml (positive rate 0%). These results indicate that the two tumor markers have no disease specificity in benign lung disease.

We reported 2 relatively rare cases of multiple primary cancer including lung cancer accompanied by old pulmonary tuberculosis. Patient 1 was a 62-year-old man admitted to our hospital for further evaluation of an infiltrative shadow on chest X-ray films, and a cervical tumor noted 10 years earlier and thought to be thyroid cancer. A Transbronchial lung biopsy (TBLB) specimen disclosed poorly differentiated squamous cell carcinoma. A right upper lobectomy and thyroidectomy were performed. Histopathologic findings showed a neoplastic lesion adjacent to caseous necrosis with formation of granuloma consistent with tuberculosis. Also, the cervical tumor was considered to be a metastatic lymph node from thyroid papillary carcinoma. Patient 2 was a 73-year-old man with a 14-year history of treatment for transitional cell carcinoma of urinary bladder, who had been admitted to our hospital for further evaluation because of a nodular shadow observed on chest X-ray films. TBLB specimens disclosed adenocarcinoma. A right upper lobectomy was performed. Histopathologic findings revealed a neoplastic tumorlet in the same lobe. No detectable increases in serum TNF-alpha, IL-1 beta or IFN-gamma were observed in either patient. Phytohemagglutinin- and concanavalin-A-stimulated lymphocyte proliferation decreased in Patient 1. These findings suggested that the immunocompromised status of patients with cancer in addition to old pulmonary tuberculosis may contribute to the development of lung cancer.

A 24-year-old man was admitted to our hospital in June 1996 with complaints of anterior chest discomfort. Chest X-ray films on admission showed an abnormal mediastinal shadow with well-defined margin. Chest X-ray examinations about 6 weeks earlier had not detected any abnormalities. Laboratory tests on admission showed a high serum concentration of Siaryl Lewis X-i antigen (SLX). A computed tomographic scan of the chest showed a large (6 x 6 x 12 cm) homogeneous mass in the right anterior mediastinum. The mass was removed completely and histologically diagnosed as a thymic cyst. Biochemical analysis of fluid from the cyst revealed remarkably high levels of SLX, CA 19-9, and CEA. In immunohistochemical studies, epithelial cells from the cystic walls stained positive for SLX, CA 19-9, and CEA. After the operation, the level of serum SLX returned almost to normal.

A 47-year-old woman was referred to our hospital because of cough and an abnormal shadow in the left lung field. The infiltrate reduced without therapy and another infiltrate appeared in the right lung field. Bronchiolitis obliterans organizing pneumonia was clinically suspected due to the absence of signs of eosinophilia in peripheral blood and bronchoalveolar lavage fluid (BALF). Open lung biopsy specimens disclosed alveolitis with mononuclear cell infiltration and organization within the air spaces of bronchioli and alveolar ducts. The observation of pronounced eosinophil infiltration in the alveolar spaces of some specimens yielded a diagnosis of eosinophilic pneumonia. After steroid therapy, the abnormal shadows disappeared. BALF lymphocyte surface marker analysis detected no decrease in the CD4/CD8 ratio; activated CD4 and CD8 lymphocytes were notably higher than the corresponding levels in peripheral blood. IL-5, IL-3, and GM-CSF values in BALF were not significantly elevated. This was a case of borderline eosinophilic pneumonia that was difficult to diagnose on the basis of clinical parameters alone.

Infection is a major complication associated with increased morbidity and mortality in patients with hepatocellular carcinoma. We compared the immunological function and nutritional status in 16 patients with hepatocellular carcinoma (13 patients had liver cirrhosis) with those of 21 normal healthy subjects.The immunological function was assessed by chemotaxis and superoxide anion production by neutrophils, phagocytosis and killing activities of neutrophils and monocytes, absolute and relative number of peripheral blood lymphocytes, the percentage of peripheral lymphocyte subsets and serum concentrations of immunoglobulins.Although the phagocytic and bactericidal activities of monocytes and superoxide production of neutrophils were not different between the groups, the phagocytic and bactericidal activities of neutrophils and the percentage of natural killer cells were significantly reduced in patients with hepatocellular carcinoma. In the latter group, the prognostic nutrition index was significantly high compared with normal subjects, indicating a poor nutritional status. The phagocytic and bactericidal activities of neutrophils were low in patients with a poor nutritional status compared to those with a good nutritional status.Our results suggest that impaired immunological competence and undernourishment may be one of the mechanisms causing increased susceptibility of patients with hepatocellular carcinoma to infection.

We encountered two patients with pulmonary cryptococcosis that resolved spontaneously without antifungal treatment. A 59-year-old man (patient 1) and 37-year-old man (patient 2) were admitted to our hospital for the examination of abnormal shadows on their chest x-ray films. Transbronchial lung biopsies were performed, and cryptococci were detected in both patient's lung tissues. Latex aggultination tests for cryptococcal antigen were positive (1:16 and 1:4, respectively). The size of the shadows reduced spontaneously and the titers of the cryptococcal antigen in sera decreased within three months although no antifungal therapy was performed. Bronchoalveolar lavage fluid (BALF) was obtained from each patient and examined. In patient 1, the lymphocyte to CD 4/8 ratio was high in the BALF obtained on admission and the lymphocyte count was low; however, the CD 4/8 ratio was still high in a BALF sample obtained 3 months after discharge. In patient 2, the findings of the BALF analysis on admission were almost normal. The analysis of BALF may contribute to the immunological conditions to in the patients with pulmonary cryptococcosis.

Cytokines in the culture supernatant of concanavalin A-stimulated macrophages/lymphocytes isolated from bronchoalveolar lavage (BAL) fluid in a 29-year-old patient with primary pulmonary cryptococcosis were evaluated to study the immune reaction against Cryptococcus neoformans in the lung. Before fungicidal therapy, levels of interferon-gamma and interleukin-10 were markedly elevated, and declined after therapy. There were no changes in interleukin-2 or interleukin-4 throughout the clinical course. This result suggests that IFN-gamma and IL-10 may be involved in the immune reaction against pulmonary cryptococcosis.

We describe a rare case of pulmonary sarcoidosis with multiple cavitation and pneumothorax. A 32-year-old woman was admitted to our hospital with a dry cough and an interstitial shadow with dense infiltrates in both upper lungs and cavitation in the right upper lung on chest roentgenogram and CT. Laboratory tests revealed an elevated level of serum lysozyme. BAL fluid demonstrated a high proportion of lymphocytes with an increased CD4/CD8 ratio, compatible with sarcoidosis. Transbronchial lung and skin biopsies showed evidence of noncaseating epithelioid-cell granuloma, and a diagnosis of sarcoidosis was made. Although pneumothorax appeared in the left lung on chest roentgenogram during clinical observation conservative treatment without corticosteroids or any other therapy for a follow-up period of 3 years resulted in improvement of her clinical condition and abnormal X-ray findings.

We describe the first case, to the best of our knowledge, of non-specific interstitial pneumonia associated with psoriasis vulgaris and polymyalgia rheumatica (PMR). A 50-year-old woman was admitted with a dry cough and a bilateral basilar reticulonodular shadows on chest X-ray. Bronchoalveolar lavage fluid analysis revealed lymphocytosis and a decreased CD4/CD8 ratio. A thoracoscopic lung biopsy specimen showed evidence of non-specific interstitial pneumonia. During her clinical course, she began suffering from psoriasis vulgaris and polymyalgia rheumatica. Corticosteroid therapy had no effect, but maintained a stable condition during a follow-up period of 4 years.

We measured serum soluble adhesion molecules levels in patients with sarcoidosis. The serum levels of soluble ICAM-land L-, E-, and P-selectin were significantly elevated in patients with sarcoidosis compared with healthy volunteers. However, there was no significant difference in serum soluble VCAM-1 levels between the patients and healthy volunteers. A significant correlation was observed between serum soluble L-selectin levels and the number of lymphocytes in the bronchoalveolar lavage fluid of patients with sarcoidosis. Although higher levels of serum soluble adhesion molecules were present in accordance with the clinical stage of sarcoidosis, the differences were not statistically significant. There was a significant correlation between serum ACE and soluble ICAM-1 or VCAM-1 levels. These findings suggest that soluble adhesion molecules may play an important role in the pathogenesis of sarcoidosis.

A 20-year-old woman was admitted to our hospital because of an abnormal shadow on a chest X-ray film. Laboratory tests done on admission showed high levels of tumor markers in serum. A computed-tomographic scan of the chest showed a multilocular cystic mass in the S10 of the right lung. Angiography revealed an abnormal artery that branched from the abdominal aorta, and therefore pulmonary sequestration was diagnosed. A right lower lobectomy was done. Analysis of fluid from the cyst revealed very high levels of CA19-9, CEA, and SLX. In an immunohistochemical study, epithelial cells of the cyst's walls were stained for CA19-9, CEA, and SLX. After the operation the levels of these tumor markers in serum were almost normal.

Chlamydia trachomatis is one of the principal pathogens for non-gonococcal urethritis. There have been a few studies about novel resistant strains isolated from the patients with genital chlamydial infection. However, the current common concept indicates that those were temporary and unstable strains with decreased antimicrobial susceptibility. Three societies, the Japanese Society of Chemotherapy, Japanese Association of Infectious Diseases and Japanese Society of Clinical Microbiology, performed the first national surveillance for C. trachomatis between April 2009 and October 2010. Based on the data obtained, the current situation of antimicrobial susceptibility in C. trachomatis and the results of the previous research on antimicrobial susceptibility in M. genitalium are discussed. In 51 medical facilities in 8 prefectures of Japan, urethral discharge or urethral swab specimens were collected from male patients with urethritis. The specimens were sent to the Kitazato University Research Center for Anti-infectious Drugs via BD Universal Viral Transport. There, measurement of antimicrobial susceptibilities was performed according to the standard method of the Japan Society of Chemotherapy. The drugs used for antimicrobial susceptibility testing are shown below. From 28 facilities, 207 specimens were collected and 48 specimens were positive for C. trachomatis by culture. Using these specimens, antimicrobial susceptibility testing could be performed for 19 strains. The MIC50, MIC90 and range (μg/ml) were as follows. EM: 0.06, 0.25, and 0.03∼0.25: CAM: 0.008, 0.016, and 0.004∼0.03; AZM: 0.125, 0.5, and 0.06∼0.5; MINO: 0.5, 1, and 0.125∼2; DOXY: 0.125, 0.25, and 0.03∼0.5 μg/ml; CPFX: 2, 4, and 1∼4; LVFX: 0.25, 0.25, and 0.125∼0.5; TFLX: 0.125, 0.25, and 0.06∼0.5; STFX: 0.06, 0.125, and 0.03∼0.25. Fortunately, there were no resistant strains of C. trachomatis in this surveillance. However, the current and future situation of antimicrobial susceptibility in the pathogens of non-gonococcal urethritis will be surveyed regularly.

To determine whether HTLV-I infection is associated with diffuse panbronchiolitis (DPB), we investigated T-cell surface markers of peripheral blood and bronchoalveolar lavage fluid (BALF) in 9 healthy volunteers, 6 HTLV-I seronegative DPB patients (HTLV-I(-)DPB) and 8 HTLV-I seropositive DPB patients (HTLV-I(+)DPB). In peripheral blood, no significant difference was observed between HTLV-I(-)DBP and healthy volunteers. However, in BALF, HTLV-I(-)DPB showed a significant decrease of the CD4/CD8 ratio and an increase of CD8+HLA-DR+ cells compared with healthy volunteers. CD3+CD25+ and CD4+HLA-DR+ cells in peripheral blood were significantly increased in HTLV-I(+)DPB compared with those in HTLV-I(-)DPB. No significant difference was observed in BALF cells between HTLV-I(-) and HTLV-I(+)DPB with the exception of CD3+CD25+ cells. The most striking result was a marked elevation of CD3+CD25+ cells in 2 of 8 HTLV-I seropositive patients. Microscopic findings of open lung biopsy specimens obtained from the 2 patients differed from the typical microscopic findings in DPB. From these findings, we consider that HTLV-I infection may be associated with pulmonary lesions like DPB, but of a different, pathologically distinct, type.

We demonstrated the efficacy of "long term" roxithromycin (RXM) treatment in 15 patients with chronic lower respiratory tract disease (11 with diffuse panbronchiolitis and 4 with sinobronchial syndrome). (1) Fourteen (93.3%) of the 15 patients showed improvement when assessed by the comprehensive improvement score, and they showed significant improvements in PaO2 (74.2 +/- 10.4 Torr to 84.3 +/- 10.9 Torr, p0.01), %VC (86.9 +/- 20.2% to 96.0 +/- 21.9%, p0.001) and FEV1 (1.81 +/- 0.87 L to 2.14 +/- 1.08 L, p0.01) after RXM treatment. (2) Neutrophils accumulated in the pre-RXM treatment bronchoalveolar lavage (BAL) fluid and decreased in BAL fluid of patients responding to RXM treatment (49.8 +/- 28.3% to 17.1 +/- 15.7%, p0.01). Additionally, the levels of interleukin 1 beta and interleukin 8 were significantly higher in BAL fluid of these patients than those in the healthy volunteers (p0.025, p0.01 respectively), and correlated with the neutrophil accumulation (r = 0.619, p0.05). These cytokines showed a decrease after RXM treatment. These results indicated that RXM acts by reducing pulmonary inflammation through reduction of neutrophil migration to inflammatory sites, and is effective on chronic lower respiratory tract disease.

To determine whether HTLV-I infection is associated with uveitis, we investigated the bronchoalveolar lavage fluid (BALF) cells in 23 patients with uveitis. Of these, sarcoidosis was diagnosed in 13 patients, but could not be confirmed in the remaining 10 patients (non-sarcoidosis). Three of 13 patients (23.1%) with sarcoidosis and 7 of 10 non-sarcoidosis patients (70.0%) were HTLV-I seropositive. In BALF, no significant differences were observed between the HTLV-I seropositive and seronegative patients. However, in non-sarcoidosis patients, total cell counts, CD3+ and CD+ HLA-DR+ cells in BALF were significantly higher in seropositive patients than in seronegative patients. CD3+ CD25+ cells in BALF were markedly increased in 3 of 7 non-sarcoidosis seronegative patients. These findings indicated that BALF lymphocytes in HTLV-I seropositive non-sarcoidosis patients were more activated than those in seronegative non-sarcoidosis patients, supporting the hypothesis that HTLV-I infection may be associated with uveitis.

It is known that tumor associated carbohydrate antigens are significantly increased in the serum of patients with diffuse panbronchiolitis (DPB). We investigated carbohydrate antigens (SLX, CA19-9) in bronchoalveolar lavage fluid (BALF) obtained from 24 patients with DPB. The concentrations of SLX and CA19-9 were significantly higher in BALF from patients with DPB than those from healthy subjects (7 cases) and patients with pulmonary sarcoidosis (16 cases). No significant correlation was observed between either SLX or CA19-9 concentrations in the serum and BALF, and no significant correlation was observed between the concentrations of these carbohydrate antigens in BALF and clinical findings. Immunohistochemical study of SLX and CA19-9 in open lung biopsy specimens obtained from patients with DPB showed expression of SLX and CA19-9 on the bronchiolar surface epithelial cells and mucinous exudates in air spances. These results indicate that carbohydrate antigens are presumably increased in the pulmonary lesions of patients with DPB, and this increase causes high levels of these antigens in the serum. Furthermore, we investigated the change of concentrations of SLX and CA19-9 in BALF obtained from patients with DPB after erythromycin (EM) treatment. The concentrations of these two antigens were decreased after EM treatment.

A sixty nine-year-old woman was admitted to the hospital because of further examination of hypercalcemia. On July 1990, she complained of general fatigue and loss of appetite. She was pointed out to have hypercalcemia (15.1mg/dl), urolithiasis, and renal insufficiency. CT films of the chest showed swelling of the mediastinal lymphnodes and CT of the abdomen nephrocalcinosis. Ga-scintigraphy demonstrated an abnormal accumulation of gallium in the mediastinum. Levels of the parathyroid hormone was normal. Levels of the serum calcium (13.7mg/dl), angiotensin converting enzyme (30.4IU/L) and 1.25 (OH)2D (87PG/ml) were elevated. Giant cells were found in the biopsy specimen of the lung. A significant relationship between the serum calcium and creatinine were observed (r = 0.76, p0.02). Proximal fractional reabsorption of sodium showed to be suppressed (47.7%), and distal fractional reabsorption of sodium showed to be normal (88.4%). From these findings hypercalcemia and urolithiasis was suggested to result from sarcoidosis. The hypercalcemia and renal insufficiency improved with corticosteroid therapy.

We investigated the long-term (3-30 months) therapeutic effects of low-dose (300-600 mg/day) erythromycin in 26 patients with diffuse panbronchiolitis (DPB). Significant improvements of pulmonary functions especially in %VC and PaO2 as well as respiratory symptoms were shown. However, erythromycin treatment was not associated with a significant change in surface phenotypes on peripheral blood lymphocytes (CD4, CD8, CD4/CD8). It is well known that serum levels of tumor-associated carbohydrate antigens such as SLX (sialylated Lewis X-i) and CA19-9 (sialylated Lewis(a)) are significantly elevated in patients with DPB. In the present study, 68.4% (13/19) of DPB patients showed marked elevation of SLX and 52.9% (9/17) showed marked elevation of CA19-9 levels in serum. These positive ratios were significantly decreased by erythromycin treatment to 31.6% (6/19) in SLX and 23.4% (4/17) in CA19-9. The mean values of each marker were also significantly decreased after erythromycin administration from 54.9 +/- 26.9 U/ml to 39.5 +/- 22.1 U/ml for SLX and from 70.5 +/- 77.4 U/ml to 28.8 +/- 37.4 U/ml for CA19-9.

Adult T-cell leukemia (ATL) is endemic in Kyushu. Our study at Hirado island in Nagasaki prefecture revealed a higher incidence (35.9%) of HTLV-I carriers in villages with fishing than in those without (16.5%). HTLV-I carriers showed a higher incidence of abnormal findings on chest roentgenogram (21.7%) than non-carriers (16.5%), but most were lesions of old pulmonary tuberculosis and pleural thickening. Virological and immunological investigations were performed for 10 HTLV-I carriers, 3 patients with HTLV-I associated myelopathy (HAM), and 3 patients with ATL to determine the presence of HTLV-I associated pulmonary disease. In HAM patients, there were high titers of anti HTLV-I antibody, positive IgA reaction to HTLV-I, and an increase in interleukin-2 receptor (IL-2)-positive T-cells in the peripheral blood; and lymphocytosis and an increase in IL-2-positive T-cells in the bronchoalveolar lavage fluid (BALF). Virological examination showed the presence of pX gene and tax1/rex1 mRNA in the peripheral blood and BALF. Similar immunological and virological findings in 2 of 10 carriers suggested the presence of HTLV-I associated pulmonary disease.

To evaluate the local immune response in lung and activity of pulmonary tuberculosis. Broncho-alveolar lavage (BAL) was performed on 15 patients with pulmonary tuberculosis. Patients consisted of nine in the active stage and six in the inactive stage. Acid-fast bacilli (AFB) in BAL fluid (BALF) were found in six out of nine active stage patients (BAL-AFB positive group). The results obtained were as follows; 1) The number of total cells in BALF increased significantly in BAL-AFB positive group. BALF from two patients of this group, who were in the very early stage, revealed that the lymphocytes increased predominantly whereas neutrophils were dominant in BALF from the other four patients. 2) No case showed increase of B cells in BALF. Lymphocytes surface markers were compared between BAL-AFB positive and negative groups. No difference was found in the numbers of OKT3, OKT4 and OKT8. The positive rates of OKIal, and OKT4/8 ratio were both increased in BALF compared to the BAL-AFB positive group. 3) The numbers of OKT4 and OKT4/8 ratio in peripheral blood, which were taken simultaneously with BAL, were decreased in patients in the active stage. 4) Protein, albumin, IgG, IgA, lysozyme and alpha 1-antitrypsin levels in BALF were all increased in tuberculous patients. No correlation between the activity of tuberculosis and levels of protein, albumin, IgG and IgA was observed. Lysozyme level increased in the inactive stage of patients. On the other hand alpha 1-antitrypsin level increased in the active stage. Fibronectin level in BALF from patients was lower than that from normal controls. 5) Smoking habit had no influence on the above results. 6) Only one case showed the appearance of new lesions after BAL procedure as a complication.

Cellular analysis including lymphocyte surface markers in BALF in 17 patients with DPB (14 male; 36 female) was performed. The total number of cells increased remarkably, especially the percentage of neutrophils (72.9 +/- 14.1%). On the contrary the percentage of alveolar macrophage decreased (15.4 +/- 8.9%). The CD4/CD8 ratio in DPB was also significantly decreased to 0.73 +/- 0.38% when compared with normal healthy nonsmokers. Five patients with low dose and long term EM treatment were analyzed. Total cell counts as well as the neutrophil percentage (7.3 +/- 4.0%) decreased significantly. On the other hand the percentage of alveolar macrophage increased to 76.6 +/- 0.6%, which was almost similar to those obtained from normal healthy volunteers. Therefore it is concluded that both clinical and BALF findings improved concordantly after EM treatment.

Tumor-associated carbohydrate antigens, CA19-9 and SLEX have been used clinically as markers for malignancy. However, it is also known that these antigens are frequently elevated in the serum of patients with benign lung diseases. We have experienced two cases of interstitial pneumonitis with marked increase of carbohydrate antigens in serum, the level of which changed according to their clinical course. Case 1. A 64-year-old woman was admitted because of a cough and exertional dyspnea. Despite treatment with various antibiotics and prednisolone, she died of respiratory failure approximately two months after admission. Her CA19-9 and SLEX in serum elevated from 500 U/ml to 5506 U/ml and 167 U/ml to 1187 U/ml respectively in accordance with clinical deterioration. Autopsy revealed no malignancy. Case 2. A 57-year-old woman, who had been suffering from interstitial pneumonitis associated with rheumatoid arthritis, was admitted with a cough and fever. She responded to prednisolone therapy, however two years later she readmitted because of exacerbation and died of respiratory failure. The initial CA19-9 level in serum was 876 U/ml and dropped to 42 U/ml with prednisolone therapy. The serum antigen level again increased during the period of exacerbation, and showed 133 U/ml immediately before death. An immunohistochemical study of CA19-9 and SLEX in various tissues obtained by autopsy was performed in case 1. The distribution of these antigens in tissue was similar to that of normal individuals. The exceptions were the expression of these antigens on epithelial cells of microscopic honeycombing and on mucinous exudates in air spaces.

A case of pulmonary sarcoidosis (stage III), in which the abnormal chest shadow disappeared within two weeks was reported. A 35-year-old male was admitted for further examination of bronchial asthma. He stayed overnight at home after he received inhalation provocation test of sulpyrin. Returning to the hospital, he had a fever (38 degrees C) with diffuse small nodular shadows on the chest roentgenogram. The onset and clinical features of the disease suggested hypersensitivity or drug induced pneumonitis rather than sarcoidosis. Bronchoalveolar lavage fluid (BALF) analysis showed an increase of total cell counts and lymphocytes. The surface marker of lymphocytes in BALF revealed that the CD4/8 ratio was remarkably elevated to 6.2. Both transbronchial lung and scalene node biopsy specimens revealed numerous non-caseous granulomas, and a diagnosis of sarcoidosis was confirmed. The chest infiltrates disappeared spontaneously within two weeks. This case was reported because of its rare natural course as stage III pulmonary sarcoidosis.

A 69-year-old man was admitted with general fatigue, dyspnea, cough, fever and right pulmonary infiltrations on a chest X-ray films. He had suffered from myocardial infarction 8 years before. Since September 1987, he had been given Aprindine in addition to previous drugs. In early November 1987, he developed dyspnea. Antibiotics were not effective. He was hospitalized on Nov. 13, '87 when crepitations were audible on his right chest. Methylprednisolone pulse therapy was effective, however right pneumothorax developed. He underwent right thoracotomy and lung biopsy. Lung biopsy specimens showed pathological features of bronchiolitis obliterans organizing pneumonia (BOOP). Corticosteroid therapy yielded a remarkable clinical, physiological and roentgenographic recovery. However, approximately two years later during prednisolone maintenance therapy, BOOP recurred. He responded again to corticosteroid treatment, however he died of hepatic failure on Dec. 17, '89. "Idiopathic" rather than "drug induced" was suggested for the cause of BOOP in this case.

MRI characteristics of number lesions were studied in eight patients with sarcoidosis proved by Ga scintigraphy. T2 weighted image in spin echo method and low flip angle method were employed. The localization of lesion detected by Ga scintigraphy was quite similar to that of lesions found by MRI, but lesions were more clearly detectable in MRI than Ga. MRI could identify anatomical localization of muscular lesions. Two characteristic MRI findings were observed; one was high intensity in the whole lesion, and another was high intensity in periphery with low intensity in central lesion. MRI is a useful tool for more accurate diagnosis of muscular lesions in sarcoidosis.