Synthesis of indano[60]fullerene thioketone and its application in organic solar cells.

Evaporable indano[60]fullerene ketone (FIDO) was converted to indano[60]fullerene thioketone (FIDS) in high yield by using Lawesson's reagent. Three compounds with different substituents in para position were successfully converted to the corresponding thioketones, showing that the reaction tolerates compounds with electron-donating and electron-withdrawing substituents. Computational studies with density functional theory revealed the unique vibrations of the thioketone group in FIDS. The molecular structure of FIDS was confirmed by single-crystal X-ray analysis. Bulk heterojunction organic solar cells using three evaporable fullerene derivatives (FIDO, FIDS, C60) as electron-acceptors were compared, and the open-circuit voltage with FIDS was 0.16 V higher than that with C60.

Relapsing polychondritis coupling with cerebral amyloid deposit inducing cerebral amyloid angiopathy-related inflammation.

Cerebral amyloid angiopathy-related inflammation is a syndrome of reversible encephalopathy with cerebral amyloid angiopathy, however the pathology is not well understood. We clear a part of the pathology through the first case of an 80-year-old man with cerebral amyloid angiopathy-related inflammation induced by relapsing polychondritis (RP) analysis. An 80-year-old man was diagnosed with RP by auricular cartilage biopsy. Almost no abnormality including intracranial microbleeding was detected by cranial magnetic resonance image (MRI) at diagnosis. However, he developed a headache and hallucination after five months. Seven-month cranial MRI showed novel, multiple, intracranial microbleeding, especially in the bilateral but asymmetry posterior, temporal, and parietal lobes. 123I-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography showed increased cerebral blood flow in the bilateral posterior lobes. After treatment, both of his neurological symptoms and increased cerebral blood flow improved to mild. Photon emission computed tomography using Pittsburgh compound B (PiB) for evaluation of brain amyloidosis at 12 months after onset showed an amyloid deposit in the bilateral frontal lobes, but a lack of uptake corresponded to the RP lesions. Our case suggests that inflammation coupled with an amyloid deposit, induced the multiple intracranial bleeding, and resulted in the lack of PiB uptake. Findings from our case show that inflammation including excess blood flow coupled with an amyloid deposit synergistically facilitate intracranial bleeding.

Antibacterial activities of persimmon extracts relate with their hydrogen peroxide concentration.

Persimmon, a deciduous tree of the family Ebenaceae, is found throughout East Asia and contains high levels of tannins. This class of natural compounds exhibit favorable toxicity profiles along with bactericidal activity without the emergence of resistant bacteria, suggesting potential medical applications. Consistent with these observations, persimmon leaves show antibacterial activity. However, the mechanism of persimmon antibacterial activity remains unknown. In the present work, we demonstrate that the antibacterial activity of persimmon reflects the generation of reactive oxygen from tannins. The identification and quantification of reactive oxygen generated from persimmon and the level of antibacterial activity were determined.

[Occupational lung diseases other than asbestos- and indium-related disease].

In our country, pneumoconiosis used to hold an overwhelmingly majority in respiratory occupational lung diseases. Although the number of pneumoconiosis cases has been decreasing certainly, new cases have been arising even today. In addition, in place of pneumoconiosis or asbestos-related diseases, occupational asthma has become the most common forms of occupational lung disease in many industrialized countries. Occupational asthma has been implicated in 9 to 15% of adult asthma in the United States. Although the environmental causes of occupational lung disease are clear, the mechanisms of the diseases are not fully understood and need to be further elucidated.

Effects of atelocollagen on neural stem cell function and its migrating capacity into brain in psychiatric disease model.

Stem cell therapy is well proposed as a potential method for the improvement of neurodegenerative damage in the brain. Among several different procedures to reach the cells into the injured lesion, the intravenous (IV) injection has benefit as a minimally invasive approach. However, for the brain disease, prompt development of the effective treatment way of cellular biodistribution of stem cells into the brain after IV injection is needed. Atelocollagen has been used as an adjunctive material in a gene, drug and cell delivery system because of its extremely low antigenicity and bioabsorbability to protect these transplants from intrabody environment. However, there is little work about the direct effect of atelocollagen on stem cells, we examined the functional change of survival, proliferation, migration and differentiation of cultured neural stem cells (NSCs) induced by atelocollagen in vitro. By 72-h treatment 0.01-0.05% atelocollagen showed no significant effects on survival, proliferation and migration of NSCs, while 0.03-0.05% atelocollagen induced significant reduction of neuronal differentiation and increase of astrocytic differentiation. Furthermore, IV treated NSCs complexed with atelocollagen (0.02%) could effectively migrate into the brain rather than NSC treated alone using chronic alcohol binge model rat. These experiments suggested that high dose of atelocollagen exerts direct influence on NSC function but under 0.03% of atelocollagen induces beneficial effect on regenerative approach of IV administration of NSCs for CNS disease.

Annual change in pulmonary function and clinical phenotype in chronic obstructive pulmonary disease.

RATIONALE: Although the rate of annual decline in FEV1 is one of the most important outcome measures in chronic obstructive pulmonary disease (COPD), little is known about intersubject variability based on clinical phenotypes. OBJECTIVES: To examine the intersubject variability in a 5-year observational cohort study, particularly focusing on emphysema severity. METHODS: A total of 279 eligible patients with COPD (stages I-IV: 26, 45, 24, and 5%) participated. We conducted a detailed assessment of pulmonary function and computed tomography (CT) at baseline, and performed spirometry every 6 months before and after inhalation of bronchodilator. Smoking status, exacerbation, and pharmacotherapy were carefully monitored. Emphysema severity was evaluated by CT and annual measurements of carbon monoxide transfer coefficient. MEASUREMENTS AND MAIN RESULTS: Using mixed effects model analysis, the annual decline in post-bronchodilator FEV1 was -32±24 (SD) ml/yr (n=261). We classified the subjects of less than the 25th percentile as Rapid decliners, the 25th to 75th percentile as Slow decliners, and greater than the 75th percentile as Sustainers (-63±2, -31±1, and -2±1 [SE] ml/yr). Emphysema severity, but not %FEV1, showed significant differences among the three groups. Multiple logistic regression analysis demonstrated that the Rapid decliners were independently associated with emphysema severity assessed either by CT or carbon monoxide transfer coefficient. The Sustainers displayed less emphysema and higher levels of circulating eosinophils. CONCLUSIONS: Emphysema severity is independently associated with a rapid annual decline in FEV1 in COPD. Sustainers and Rapid decliners warrant specific attention in clinical practice.

Age-dependent treatment effect of vocal fold steroid injection for benign vocal fold lesions.

Objective: Benign vocal fold lesions (BVFLs) cause voice disorders and impair social life. Recently, office-based vocal fold steroid injection (VFSI) has gained attention as a minimally invasive treatment for BVFLs. This study aimed to analyze the age-dependent treatment effect of VFSI and to clarify the indications for treatment. Methods: In this retrospective cohort study, a total of 83 patients with BVFLs were treated with a similar regimen of VFSI. Three or four months after the injection, age-dependent phonological functions were evaluated. The differences between pre- and post-treatment findings were analyzed using the Wilcoxon matched-pair signed-rank test, and the correlation between patient age and improvement rates were determined by Pearson's correlation coefficient. Results: Improvement in voice handicap index (VHI), which was the primary endpoint, was observed. Subjective and objective voice quality measurements also showed significant improvements. Subgroup analyses revealed that there was no age-related difference in the improvement of voice quality and that there was no improvement in aerodynamic effect in patients over 45 years of age. Conclusion: This study clarified the age-dependent treatment effect of VFSI and provided the important suggestion of establishing indication criteria for BVFLs. The study results provided clarity on the indication criteria of VFSI and served as an important indicator for tailoring treatment to patients' needs. Level of Evidence: 4.

Antimicrobial and osteogenic properties of a hydrophilic-modified nanoscale hydroxyapatite coating on titanium.

Hydroxyapatite (HA)-coated titanium (Ti) is commonly used for implantable medical devices. This study examined in vitro osteoblast gene expression and antimicrobial activity against early and late colonizers of supra-gingival plaque on nanoscale HA-coated Ti prepared by discharge in a physiological buffered solution. The HA-coated Ti surface showed super-hydrophilicity, whereas the densely sintered HA and Ti surfaces alone showed lower hydrophilicity. The sintered HA and HA-coated Ti surfaces enhanced osteoblast phenotypes in comparison with the bare Ti surface. The HA-coated Ti enabled antimicrobial activity against early colonizers of supra-gingival plaques, namely Streptococcus mitis and Streptococcus gordonii. Such antimicrobial activity may be caused by the surface hydrophilicity, thereby leading to a repulsion force between the HA-coated Ti surface and the bacterial cell membranes. On the contrary, the sintered HA sample was susceptible to infection of microorganisms. Thus, hydrophilic-modified HA-coated Ti may have potential for use in implantable medical devices. From the Clinical Editor: This study establishes that Hydroxyapatite (HA)-coated titanium (Ti) surface of implanted devices may result in an optimal microenvironment to control and prevent infections and may have potential future clinical applications.

Contribution of hly homologs to the hemolytic activity of Prevotella intermedia.

Prevotella intermedia is a periodontal pathogen that requires iron for its growth. Although this organism has hemolytic activity, the precise nature of its hemolytic substances and their associated hemolytic actions are yet to be fully determined. In the present study, we identified and characterized several putative hly genes in P. intermedia ATCC25611 which appear to encode hemolysins. Six hly genes (hlyA, B, C, D, E, and hlyI) of P. intermedia were identified by comparing their nucleotide sequences to those of known hly genes of Bacteroides fragilis NCTC9343. The hlyA-E, and hlyI genes were overexpressed individually in the non-hemolytic Escherichia coli strain JW5181 and examined its contribution to the hemolytic activity on sheep blood agar plates. E. coli cells expressing the hlyA and hlyI genes exhibited hemolytic activity under anaerobic conditions. On the other hand, only E. coli cells stably expressing the hlyA gene were able to lyse the red blood cells when cultured under aerobic conditions. In addition, expression of the hlyA and hlyI genes was significantly upregulated in the presence of red blood cells. Furthermore, we found that the growth of P. intermedia was similar in an iron-limited medium supplemented with either red blood cells or heme. Taken together, our results indicate that the hlyA and hlyI genes of P. intermedia encode putative hemolysins that appear to be involved in the lysis of red blood cells, and suggest that these hemolysins might play important roles in the iron-dependent growth of this organism.

Rapid detection and identification of Streptococcus ratti by a species-specific PCR method.

To establish a rapid and species-specific detection and identification method of Streptococcus ratti by polymerase chain reaction, two PCR primer pairs specific to S. ratti were designed on the basis of the nucleotide sequence of the dextranase gene (dex) of S. ratti ATCC19645(T). The primer pairs specifically detected S. ratti, but none of the other mutans streptococci (16 strains of 6 species). The PCR procedure was capable of detecting 1 pg of genomic DNA purified from S. ratti ATCC19645. We developed the Streptococcus mutans-, Streptococcus sobrinus-, Streptococcus downei- and Streptococcus salivarius-specific PCR methods (the dex PCR methods) with the primer pairs specific for a portion of the dex gene of each species. The mixture of these primer pairs including S. ratti (this study) successfully differentiated the five species of mutans streptococci by species-specific amplicons of different lengths. These results suggest that the present PCR method is suitable for the specific detection and identification of S. ratti, and that the mixture of primer pairs for the dex PCR methods is useful for species-specific detection and rapid discrimination of each species in mutans streptococci.

Surface lipoprotein PpiA of Streptococcus mutans suppresses scavenger receptor MARCO-dependent phagocytosis by macrophages.

Streptococcus mutans is associated with the initiation and progression of human dental caries and is occasionally isolated from the blood of patients with bacteremia and infective endocarditis. For the pathogen to survive in the infected host, surface lipoproteins of S. mutans are likely to play important roles in interactions with the innate immune system. To clarify the role that a putative lipoprotein, peptidyl-prolyl cis/trans-isomerase (PpiA), of S. mutans plays in the macrophage response, we investigated the response of THP-1-derived macrophages to S. mutans challenge. The deletion of the gene encoding Lgt eliminated PpiA on the cell surface of S. mutans, which implies that PpiA is a lipoprotein that is lipid anchored in the cell membrane by Lgt. Human and murine peritoneal macrophages both showed higher phagocytic activities for the ppiA and lgt mutants than the wild type, which indicates that the presence of PpiA reduces S. mutans phagocytosis. In addition, infection with S. mutans markedly induced mRNAs of macrophage receptor with collagenous structure (MARCO) and scavenger receptor A (SR-A) in human macrophages. In particular, transcriptional and translational levels of MARCO in human macrophages infected with the ppiA mutant were higher than those in macrophages infected with the wild type. Phagocytosis of S. mutans by human macrophages markedly decreased after treatment with anti-MARCO IgG. These results demonstrate that the S. mutans lipoprotein PpiA contributes to suppression of MARCO-mediated phagocytosis of this bacterium by macrophages.

[Promising therapy of neural stem cell transplantation for FASD model--neural network reconstruction and behavior recovery].

OBJECTIVES: It has been elucidated that psychiatric disorders are associated with impairment of the brain neural network. Reduction in brain size and hypoplasia of the basal ganglia and corpus callosum have been reported in Fetal Alcohol Spectrum Disorder (FASD). It is believed that the formation of the neural network is influenced by alcohol exposure during the fetal period. Additionally, it is well known that the functional expression of CNS consequences of prenatal alcohol exposure includes cognitive and attentional processes, as well as social behavioral problems. It has also been reported that abnormal 5-HT neuron development can be reversed by treatment with a 5-HT1A agonist in a prenatal alcohol exposure model. However, these treatments are prophylactic. Without early intervention, the consequences of FASD are permanent. Recently, emerging evidence suggest that many clinical symptoms observed in psychiatric disease are likely related to neural network disruptions including neurogenesis dysfunction. Neural stem cell (NSC) transplantation has been investigated in areas such as brain injury, stroke and neurodegenerative diseases and may be a way to reverse neurogenesis dysfunction. In the present work, we evaluated the usefulness of intravenous transplantation of NSCs in the FASD model rat focusing on the possibility of regenerative therapy, particularly regarding behavioral abnormalities, for FASD rats. RESULTS: Abnormal behaviors FASD model rats suggest that reduced social activity , and cognitive dysfunction are major symptoms in FASD patients. Intravenous NSC transplantation appeared to partially correct these behavioral abnormalities in FASD model rats. In the Amygdala areas intravenous NSC transplantation appears to have partially regaenerates expression of PSD95 in FASD model rats. CONCLUSIONS: The results suggest that intravenous NSC transplantation may be an advanced approach to recover neural network damage and CNS dysfunction in FASD and possibly other psychiatric disorders.

Successful endovascular coiling of infectious cerebral aneurysm following Staphylococcus haemolyticus endocarditis.

Recent reports suggest that Staphylococcus haemolyticus can cause infective endocarditis (IE). However, no data are available regarding infectious intracranial aneurysm (IIA) following S. haemolyticus endocarditis. Endovascular coiling is a challenging approach for the treatment of IIA. We describe the case of a 63-year-old woman who suddenly developed aphasia and dysarthria following an acute cerebral infarction in her left insular and temporal cortex. After a total hysterectomy at the age of 39, the patient had suffered from recurrent bacterial pyomyositis in her legs. At admission, there was no evidence of cerebral aneurysm, as assessed by magnetic resonance angiography, and no vegetation, as assessed by transesophageal echocardiography (TEE), resulting in an incorrect diagnosis. However, subarachnoid hemorrhage and development of cerebral aneurysm in the left middle cerebral artery occurred within 1 week of hospitalization. Continuous positive blood culture results and a second TEE finally revealed that IE was caused by S. haemolyticus. Coil embolization of the IIA was successful on day 26 after symptom onset; after this procedure, the patient began to recover. This case demonstrates that S. haemolyticus-induced endocarditis can cause IIA. Endovascular coiling is a potentially effective approach to treat IIA.

Noteworthy Cardiovascular Involvement with Sporadic Late-onset Nemaline Myopathy.

Cardiac involvement has recently been the focus of sporadic late-onset nemaline myopathy (SLONM). However, right ventricular failure and pulmonary hypertension, in addition to repetitive cardiac arrest, are noteworthy characteristics of SLONM. We herein report a 66-year-old woman with SLONM whose main symptoms were cardiac arrest, right ventricular failure, and pulmonary hypertension. Despite permanent pacemaker replacement, cardiac arrest occurred repetitively, and even with continuous positive airway pressure, right ventricular failure and pulmonary hypertension persisted. The patient was finally diagnosed with SLONM by a muscle biopsy. Our case suggests the possibility of cardiovascular involvement in SLONM, especially right ventricular failure and pulmonary hypertension.

Unique Mortality Profile in Japanese Patients with COPD: An Analysis from the Hokkaido COPD Cohort Study.

Purpose: Causes of death may be unique and different in Japanese patients with COPD because they are generally older, thinner, experience fewer exacerbations, and live longer than those in other countries. We investigated the detailed mortality profile in the Hokkaido COPD cohort study, which completed a 10-year follow-up with a very low dropout rate. Patients and Methods: We prospectively examined the 10-year natural history in 279 Japanese patients with COPD (GOLD 1, 26%; GOLD 2, 45%; GOLD 3, 24%; and GOLD 4, 5%). The majority of patients were male, and the average age at baseline was 69 years old. About 95% of all patients had accurate mortality data. The risk factors for mortality were also analyzed. Results: During the 10 years, 112 patients (40%) died. Their median survival time was 6.1 years (interquartile range: 4.7-7.9 years), and age at death was 79 ± 6 years old (mean ± SD). Respiratory diseases, including pneumonia, were the leading causes of death in 45 (40%), followed by lung cancer in 24 (21%), other cancers in 18 (16%), and cardiovascular diseases in 12 (11%). In particular, lung cancer-related death was equally distributed across all COPD stages, with a higher proportion of lung cancer in the relatively younger generation (<64 years old). Older age at baseline, lower BMI, and severer emphysema were significant risk factors for all-cause mortality. Conclusion: The unique mortality profile observed in this study should be considered when designing strategies for the management of patients with COPD in any geographic region.

Annual change in FEV1 in elderly 10-year survivors with established chronic obstructive pulmonary disease.

Long-term decline in lung function is generally considered to be progressive in individuals with established chronic obstructive pulmonary disease (COPD), despite the presence of intersubject variation. We hypothesized that the annualized rate of decline in forced expiratory volume in 1 second (FEV1) would not be constant among different time periods in the natural history of established COPD. We compared the annual change rates in FEV1 during the first 5 years and the last 5 years, estimated separately using a linear mixed-effects model in 10-year survivors (n = 110). The subjects were classified into three FEV1 decline groups, based on the 25th and 75th percentile values in each time period. The rates of FEV1 changes, calculated from the first 5 years and the last 5 years, did not correlate with each other among 10-year survivors; the subjects of each FEV1 decline group during the first 5 years did not consistently remain in the same FEV1 decline group during the last 5 years. Smoking status and exacerbation frequency were not associated with decline in FEV1. In conclusion, the disease activity, which is often expressed as annualized change in FEV1, might be changeable either way over years in patients with established COPD.

Determination of reactive oxygen generated from natural medicines and their antibacterial activity.

Extracts of 16 natural medicine powders (Galla chinensis, Malloti cortex, Cassiae semen, Sophorae radix, Myricae cortex, Crataegi fructus, Gambir, Mume fructus, Geranii herba, Phellodendri cortex, Coptidis rhizoma, Swertiae herba, and Cinnamomi cortex) were assayed for reactive oxygen concentrations using the peroxyoxalate chemiluminescent detection system. High luminescence intensity was observed in Galla chinensis, Geranii herba, Malloti cortex, Myricae cortex, and Cinnamomi cortex. Additional experiments identified the reactive oxygen species as hydrogen peroxide. Galla chinensis generated 2.4×10-4 mol/L hydrogen peroxide from a 1 mg/mL solution. In bacterial growth tests, Galla chinensis extract had antibacterial activity against Escherichia coli, Staphylococcus aureus, Bacteroides thetaiotaomicron, Campylobacter sputorum biovar sputorum, Streptococcus salivarius thermophilus, Lactobacillus casei, and Bifidobacterium longum infantis. This antibacterial activity was decreased by the addition of catalase. It revealed that hydrogen peroxide which Galla chinensis produced participated in antibacterial activity.

[Clinical analysis of home oxygen therapy in patients with pneumoconiosis at Iwamizawa Rosai Hospital].

Although home oxygen therapy (HOT) has become one of the standard therapies in the management of chronic respiratory failure, especially for patient with hypoxia, there are very few studies about HOT in patients with pneumoconiosis. Therefore, we clinically investigated the characteristics of 97 patients with pneumoconiosis and 30 patients with COPD on home oxygen therapy (HOT) followed at Iwamizawa Rosai Hospital during the period from 1990 to 2003. The mean survival time in patients with pneumoconiosis (42 months) by the Kaplan-Meier method was shorter than in patents with COPD (75 months). Among the patients with pneumoconiosis divided by chest radiography classification of pneumoconiosis, there was no significant difference in mean survival time. The survival time in pneumoconiosis patients with dyspnea grade IV was shorter than in patients with dyspnea grade III.

Detection of cariogenic bacterial genes by microchip electrophoresis.

Allele-specific PCR primers were designed, based on the dextranase (dex) gene, to identify Streptococcus mutans and Streptococcus sobrinus in dental plaque; subsequently, PCR products were detected via microchip electrophoresis (ME). In order to amplify the dex gene fragment of S. mutans and S. sobrinus, the following two PCR methods were established. Duplex allele-specific PCR primers were designed on a region of low DNA homology; furthermore, 211 and 126-bp fragments were amplified for S. mutans and S. sobrinus, respectively. Common PCR primer for single allele-specific PCR was designed so as to sandwich a region exhibiting high homology and amplify PCR product of different DNA size due to deletion of small DNA fragment in two dex genes. S. mutans and S. sobrinus were amplified, leading to the generation of 202 and 226-bp products, respectively. Analysis of DNA base size by ME in order to achieve efficient separation employed a polymer mixture consisting of hydroxypropyl methylcellulose (HPMC) and polyethylene oxide (PEO). In the presence of a polymer mixture of 0.125% PEO/0.6% HPMC, two PCR products were obtained, displaying degree of separation of 226 bp/202 bp of 2.67 (Rs). Reproducibility (CV%, n = 7) was 0.3%; additionally, separation time was approximately 85 s. This method was applied to the detection of S. mutans and S. sobrinus in dental plaque. Detection of the dex genes of S. mutans and S. sobrinus characterized by quickness, precision and high sensitivity was possible.

[A case of chronic pulmonary paracoccidioidomycosis].

In a 43-year-old Japanese Brazilian who came to Japan in 2001, since subjective symptoms such as cough, sputum, and dyspnea on exertion had become severe, he was referred to our hospital because of suspicion of pulmonary tuberculosis in chest radiography and CT findings. A chest radiograph of initial examination showed interstitial shadows in both lungs with nodular, infiltrative or cavitary changes. No Mycobacterium tuberculosis was found. The mycetocyte with multipolar budding resembling the steerage of a ship, which was characteristic of Paracoccidioides was observed in sputum and transbronchial lung biopsy specimens. We cultured a fungus to show dimorphism of temperature dependency, and a diagnosis of chronic lung paracoccidioidomycosis was arrived at. By administration of ITCZ 200 mg/day, the chest radiography findings and clinical manifestations were improved. This case seems to be worthy of reporting in Japan since the affected site or organ was limited to the two lungs with multiple cavitary lesions and fibrotic changes on radiographic examination, and final diagnosis was made by cytology of sputum and pathology of TBLB specimens.