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.

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.

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.

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.

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.

Role of protease maturation lipoprotein in osmoadaptation of Streptococcus mutans.

Osmoadaptation may be an important trait for the pathogenicity of Streptococcus mutans. However, how this organism adapts to changes in osmolality in the oral cavity remains unclear. In this study, we showed that S. mutans utilizes K(+) for osmoadaptation, in which protease maturation lipoprotein (PrtM) plays an important role. Although growth of the wild-type strain was impaired in a hyperosmotic medium [brain heart infusion (BHI) containing 0.3 M NaCl] compared with that in an unmodified BHI, the prtM mutant grew much more poorly in 0.3 M NaCl BHI. Comparison of growth behavior in the hyperosmotic medium supplemented with different osmoprotectants revealed that only the addition of K(+) allowed the bacteria to overcome the impairment of growth caused by the high osmolality. These results suggest that K(+) is an important compatible solute for S. mutans. Moreover, K(+) -associated recovery of growth was not observed for the prtM mutant, indicating that PrtM plays a critical role in the utilization of K(+) . Quantitative reverse-transcriptase polymerase chain reaction analysis showed that prtM was induced by osmotic stress, implying that prtM is an osmoresponsive gene. These findings suggest that K(+) is an important compatible solute for S. mutans, and that the osmoresponsive lipoprotein PrtM is involved in K(+) utilization, contributing to osmoadaptation of S. mutans.

[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.

Recovery of acetic acid from dilute aqueous solutions using catalytic dehydrative esterification with ethanol.

We have developed a direct esterification of aqueous acetic acid with ethanol (molar ratio=1:1) catalyzed by polystyrene-supported or homogeneous sulfonic acids toward the recovery of acetic acid from wastewater in chemical plants. The equilibrium yield was significantly increased by the addition of toluene, which had a high ability to extract ethyl acetate from the aqueous phase. It was shown that low-loading and alkylated polystyrene-supported sulfonic acid efficiently accelerated the reaction. These results suggest that the construction of hydrophobic reaction environments in water was critical in improving the chemical yield. Addition of inorganic salts was also effective for the reaction under not only biphasic conditions (toluene-water) but also toluene-free conditions, because the mutual solubility of ethyl acetate and water was suppressed by the salting-out effect. Among the tested salts, CaCl(2) was found to be the most suitable for this reaction system.

Identification and functional analysis of the gene cluster for fructan utilization in Prevotella intermedia.

Fructanase enzymes hydrolyze the ß-2,6 and ß-2,1 linkages of levan and inulin fructans, respectively. We analyzed the influence of fructan on the growth of Prevotella intermedia. The growth of P. intermedia was enhanced by addition of inulin, implying that P. intermedia could also use inulin. Based on this finding, we identified and analyzed the genes encoding a putative fructanase (FruA), sugar transporter (FruB), and fructokinase (FruK) in the genome of strain ATCC25611. Transcript analysis by RT-PCR showed that the fruABK genes were co-transcribed as a single mRNA and semi-quantitative analysis confirmed that the fruA gene was induced in response to fructose and inulin. Recombinant FruA and FruK were purified and characterized biochemically. FruA strongly hydrolyzed inulin, with slight degradation of levan via an exo-type mechanism, revealing that FruA is an exo-ß-d-fructanase. FruK converted fructose to fructose-6-phosphate in the presence of ATP, confirming that FruK is an ATP-dependent fructokinase. These results suggest that P. intermedia can utilize fructan as a carbon source for growth, and that the fructanase, sugar transporter, and fructokinase proteins we identified are involved in this fructan utilization.

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.

Lipoproteins of Actinomyces viscosus induce inflammatory responses through TLR2 in human gingival epithelial cells and macrophages.

Actinomyces viscosus has been suggested to be associated with periodontal disease. However, the pathogenicity of this bacterium is not known. In this study, we examined inflammation-inducing activity by A. viscosus. Whole cells and a lipophilic fraction of A. viscosus ATCC19246 induced production of interleukin-8 and tumor necrosis factor alpha from both human oral epithelial cells and human monocytoid cells. This cytokine production was blocked by lipoprotein lipase treatment of the lipophilic fraction. In addition, anti-Toll-like receptor 2 antibody blocked the cytokine production. These results suggest that lipoprotein of A. viscosus triggers inflammatory responses in periodontitis by activation of Toll-like receptor 2.

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.

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.

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.

Norbornadiene End-Capping of Cross-Coupling Polymerizations: A Facile Route to Triblock Polymers.

The potential use of conjugated polymers in device applications is often limited by their less than optimal physicochemical properties. This work describes an efficient protocol to end-cap conjugated polymers synthesized via palladium-catalyzed cross-coupling polymerizations with norbornene groups. Specifically, the hydroarylation of norbornadiene is shown to be a high-yielding end-capping method. These strained bicyclic alkenyl end groups can be transformed into macroinitiators via ring-opening metathesis polymerization and can polymerize other strained monomers, such as norbornene, yielding elastomeric triblock copolymers.

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.