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Volume 220 (2010)
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Volume 220, Issue 1
January
Displaying 1-12 of 12 articles from this issue
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Editorial Overview
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Shigeki Shibahara2010 Volume 220 Issue 1 Pages 1-2
Published: 2010
Released on J-STAGE: December 29, 2009
JOURNAL FREE ACCESSDownload PDF (126K)
Invited Review for the 90th Anniversary
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Hajime Isomoto, Joel Moss, Toshiya Hirayama2010 Volume 220 Issue 1 Pages 3-14
Published: 2010
Released on J-STAGE: December 29, 2009
JOURNAL FREE ACCESSHelicobacter pylori produces a vacuolating cytotoxin, VacA, and most virulent H. pylori strains secrete VacA. VacA binds to two types of receptor-like protein tyrosine phosphatase (RPTP), RPTPα and RPTPβ, on the surface of host cells. VacA bound to RPTPβ, relocates and concentrates in lipid rafts in the plasma membrane. VacA causes vacuolization, membrane anion-selective channel and pore formation, and disruption of endosomal and lysosomal activity in host cells. Secreted VacA is processed into p33 and p55 fragments. The p55 domain not only plays a role in binding to target cells but also in the formation of oligomeric structures and anionic membrane channels. Oral administration of VacA to wild-type mice, but not to RPTPβ knockout mice, resulted in gastric ulcers, in agreement with the clinical effect of VacA. VacA with s1/m1 allele has more potent cytotoxic activity in relation to peptic ulcer disease and appears to be associated with human gastric cancer. VacA activates pro-apoptotic Bcl-2 family proteins, and induces apoptosis via a mitochondria-dependent pathway. VacA can disrupt other signal transduction pathways; VacA activates p38 MAPK, enhancing production of IL-8 and PGE2, and PI3K/Akt, suppressing GSK-3β activity. VacA has immunomodulatory actions on T cells and other immune cells, possibly contributing to the chronic infection seen with this organism. H. pylori virulence factors including VacA and CagA, which is encoded by cytotoxin-associated gene A, along with host genetic and environmental factors, constitute a complex network to regulate chronic gastric injury and inflammation, which is involved in a multistep process leading to gastric carcinogenesis.View full abstractDownload PDF (1935K)
Regular Contributions
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Monolayer Culture Systems with Respiratory Epithelial Cells for Evaluation of Bacterial InvasivenessYoichi Hirakata, Hisakazu Yano, Kazuaki Arai, Shiro Endo, Hajime Kanam ...2010 Volume 220 Issue 1 Pages 15-19
Published: 2010
Released on J-STAGE: December 29, 2009
JOURNAL FREE ACCESSPseudomonas (P.) aeruginosa is a major opportunistic pathogen especially in immunocompromised patients. To evaluate the invasiveness of respiratory pathogens, we developed monolayer culture systems and examined the degree of invasion by P. aeruginosa and invasive Salmonella (S.) typhimurium strains using human respiratory cell lines: A549 (derived from lung cancer), BEAS-2B (normal bronchial epithelium), and Calu-3 (pleural effusion of a patient with adenocarcinoma of the lung). Cells were seeded into filter units containing 0.33 cm2 filter membranes with 3.0 μm pores, and were incubated at 37°C under 5% CO2 for 4-10 days. By monitoring the trans-monolayer electrical resistance (TER), we judged that BEAS-2B cells (TER values: 436.2 ± 16.8 to 628.8 ± 66.3 Ω cm2) and Calu-3 cells (TER values: 490.5 ± 25.2 to 547.8 ± 21.6 Ω cm2) formed monolayers with tight junctions, but not A549 cells. On day 8 of culture, monolayer cultures were infected with bacteria, and the number of microorganisms penetrating into the basolateral medium was counted. Wild-type P. aeruginosa PAO1 (PAO1 WT) and S. typhimurium SL1344 were detected in the basolateral medium of BEAS-2B monolayer system by 3 h after inoculation, while only P. aeruginosa PAO1 WT was detected in the basolateral medium of Calu-3 monolayer, indicating poor invasiveness of S. typhimurium SL1344 in the Calu-3 system. These findings suggest that BEAS-2B or Calu-3 monolayer system could be useful for evaluating the invasiveness of respiratory pathogens. Because of the difference in bacterial invasiveness, we may need to choose a suitable cell system for each target pathogen.View full abstractDownload PDF (595K) -
Heinner Guio, Yugo Ashino, Hiroki Saitoh, Umme Ruman Siddiqi, Masako M ...2010 Volume 220 Issue 1 Pages 21-25
Published: 2010
Released on J-STAGE: December 29, 2009
JOURNAL FREE ACCESSLatent tuberculosis infection (LTBI) is defined as an infection with Mycobacterium tuberculosis (MTB) without clinical, bacteriological, or radiological findings, and its early diagnosis is essential for eradication of tuberculosis. To identify LTBI, we measured the numbers of interferon-γ producing T cells, based on the ELISPOT assay, and the antibody titers in the sera to tuberculous glycolipid antigen (TBGL-Ab). Seventeen culture-confirmed TB patients, 13 controls from TB endemic areas (EC) and 13 controls from TB non-endemic areas (NEC) were enrolled. Peripheral blood mononuclear cells (2.5 × 105 per well) were cultured on plates precoated with antibody against interferon-γ. ELISPOT response was defined as positive when the MTB-specific antigen-containing wells showed at least 6 spots and twice numbers of spots than negative control wells. ELISPOT responses were positive in 15 (88%), 8 (62%) and 4 (31%) subjects of TB, EC and NEC groups, respectively. The ELISPOT data differ between TB and NEC groups (p < 0.01) but not between TB and EC groups. In contrast, TBGL-Ab titers were elevated (> 2.0 U/ml) in 12 TB patients (71%), but only in one subject (8%) each from EC and NEC groups. These results indicate the high prevalence of LTBI in EC. In conclusion, LTBI is associated with positive ELISPOT assay and the low titer of TBGL-Ab, while positive results both in ELISPOT and TBGL-Ab assays indicate active TB. The low titer of TBGL-Ab is a helpful marker to identify LTBI in ELISPOT-positive individuals in TB endemic areas.View full abstractDownload PDF (265K) -
Susanne Thümmler, Didier Dupont, Cécile Acquaviva, Toshiyu ...2010 Volume 220 Issue 1 Pages 27-31
Published: 2010
Released on J-STAGE: December 29, 2009
JOURNAL FREE ACCESSMitochondrial acetoacetyl-CoA thiolase (T2) catalyzes 2-methylacetoacetyl-CoA cleavage into acetyl-CoA and propionyl-CoA in isoleucine catabolism and interconversion between acetyl-CoA and acetoacetyl-CoA in ketone body metabolism. T2 deficiency is a rare metabolic disease of autosomal recessive inheritance. The disorder is characterized by intermittent ketoacidotic episodes. The onset of clinical symptoms is in the infant or toddler period. The frequency of episodes declines with age, stopping before adolescence. Here we report two siblings with this disorder. The proband (GK65) is a French girl born from non-consanguineous parents. She presented several ketoacidotic episodes with 5 hospitalizations from age 2 to 4 years, the first of them complicated by ketoacidotic coma. Minor episodes, which are generally provoked by infections or high protein intake, still persist at age of 16 years. Molecular analysis of the T2 gene has revealed the compound heterozygosity of c.578T>C (M193T) and IVS8+5g>t. The latter mutation results in skipping of exon 8. In contrast, the younger brother (GK65b) had a unique ketoacidotic crisis at the age of 6 years that is the oldest-age first crisis among T2-deficient patients reported thus far. Despite the mild phenotype, he carried the same T2 gene mutations as his sister (GK65). Furthermore, T2 catalytic activity and T2 protein were not detected in the fibroblasts derived from GK65 and GK65b. In conclusion, the siblings with the same T2 gene mutations present different clinical severity. Diagnostic testing for asymptomatic siblings is important in the management of T2-deficient families.View full abstractDownload PDF (504K) -
YuanHong Shi, ZaiWang Li, SuMing Zhang, MinJie Xie, XiangWu Meng, JinZ ...2010 Volume 220 Issue 1 Pages 33-40
Published: 2010
Released on J-STAGE: December 29, 2009
JOURNAL FREE ACCESSThe most common site of hemorrhage is the basal ganglia, which exhibits the obvious neurological deficits. In the present study, we aimed to develop a model of supratentorial intracerebral hemorrhage (ICH) with neurological deficits in piglets (6.0 to 8.8 kg). A pediatric urinary catheter with two passages and one balloon was introduced through a burr hole into the right striatum. All the animals received balloon inflation, which was performed by injecting 2.5 ml saline into the balloon through one passage. Then each piglet in experimental group (n = 18) received an injection of 1.0-ml autologous arterial blood through the other passage over 2 min and maintained for 5 min. Then, additional 1.5-ml blood was injected over 15 min. Piglets in control group (n = 6) received only balloon inflation without blood injection. CT scanning was performed immediately after surgery. A deep hematoma was successfully induced in 16 out of 18 piglets and the hematoma volume was 1.74 ± 0.22 ml (n = 5) at 24 hours after surgery. All the piglets with hematoma had behavioral deficits (lame or could not walk) at 24 hours. Tissue damages, such as cell swelling, necrosis and demyelization, appeared at 24 hours in the brain tissues, adjacent to the hematoma, and was aggravated at 48 hours and ameliorated at 7 days after hematoma induction. In conclusion, we have established a simple model of supratentorial ICH in piglets with marked neurological deficits, which is suitable for study of the pathophysiology and treatment of ICH.View full abstractDownload PDF (1788K) -
Kenichiro Ozaki, Hitoshi Kagaya, Michio Yokoyama, Eiichi Saitoh, Sumik ...2010 Volume 220 Issue 1 Pages 41-46
Published: 2010
Released on J-STAGE: December 29, 2009
JOURNAL FREE ACCESSVideofluoroscopic examination of swallowing (VF) is the gold standard in diagnosis and management of dysphagia. During VF, the patient ingests radiopaque foods and liquids, and oral, pharyngeal, and esophageal stages of swallowing physiology are observed and evaluated. Aspiration is defined as passage of materials through the vocal folds, and laryngeal penetration is defined as passage of materials into the larynx, but not through the vocal folds. In this study, we compared the risk of laryngeal penetration or aspiration during VF using various liquid volumes and food consistencies. Between January 2006 and September 2008, 229 patients with suspected dysphagia each were fed at least 2 out of 6 types of liquids or foods during VF in an upright posture without compensatory maneuvers. The 6 types were pudding-thick barium of 4 ml (PD), thin liquid barium of 4 ml (LQ4) and 10 ml (LQ10), one swallow of thin liquid barium from a cup (CUP), corned beef hash (8 g) with barium (CB), and a two-phase mixture of corned beef hash (4 g) with barium and thin liquid barium of 5 ml (MX). The paired comparisons revealed that laryngeal penetration risk increased in the following order: PD, CB, LQ4, LQ10, MX and CUP, while aspiration risk after PD increased in the following order: CB, LQ4, LQ10, CUP and MX. Thus, risk of laryngeal penetration or aspiration varies, depending on food types. In conclusion, risk of aspiration is highest with the two-phase food, and multi-textured foods should be used with caution in individuals with dysphagia.View full abstractDownload PDF (447K) -
Kazumasa Suzuki, Katsushi Nishimaki, Kaori Okuyama, Tadashi Katoh, Min ...2010 Volume 220 Issue 1 Pages 47-57
Published: 2010
Released on J-STAGE: December 29, 2009
JOURNAL FREE ACCESSStreptococcus pneumoniae is a common cause of respiratory tract infections (RTIs). The prevalence of Streptococcus pneumoniae strains with reduced susceptibility to antimicrobial agents has dramatically increased worldwide. Susceptibility to nine antimicrobial agents and serotypes were determined among 1,644 Streptococcus pneumoniae strains isolated from patients with RTIs in the Tohoku district of Japan from October to December every year from 1998 to 2007. The prevalence of penicillin G-nonsusceptible Streptococcus pneumoniae (PNSP) strains increased gradually from 48.5% in 1998, reached a statistical peak in 2004 (65.1%) and then decreased to 51.5% in 2007. Streptococcus pneumoniae strains with each serotype 3, 6, 19 and 23 were constantly detected, and the distribution of these serotypes in PNSP strains did not significantly change during the study period. A trend of Streptococcus pneumoniae strains nonsusceptible to other β-lactams tested was similar to that of PNSP strains, except for cefditoren, to which the resistance rate was < 20% throughout the analysis period. The prevalence of strains nonsusceptible to erythromycin and minocycline were consistently > 60%. Almost all penicillin G-resistant Streptococcus pneumoniae (PRSP) strains were resistant to both erythromycin and minocycline throughout the analysis period. The prevalence of strains resistant to fluoroquinolones tested were < 3% over the study period. Our longitudinal surveillance demonstrated for the first time that decreased prevalence of both β-lactam- and multidrug-resistant strains has been occurring since 2004 in a region of Japan. Careful monitoring of antimicrobial susceptibility of Streptococcus pneumoniae should be continued.View full abstractDownload PDF (572K) -
Hiroshi Mukae, Kanako Urabe, Katsunori Yanagihara, Hiroshi Ishimoto, N ...2010 Volume 220 Issue 1 Pages 59-65
Published: 2010
Released on J-STAGE: December 29, 2009
JOURNAL FREE ACCESSPseudomonas (P.) aeruginosa frequently colonizes the respiratory tract of patients with chronic respiratory tract infections such as diffuse panbronchiolitis (DPB). The number of dendritic cells (DCs) that play a central role in immune functions as antigen-presenting cells is reportedly increased in the bronchiolar tissues of patients with DPB. However, the functions of DCs in chronic P. aeruginosa respiratory tract infection have not been defined. Here, we assessed the functions of DCs and the effect of macrolide antibiotics that are therapeutic agents for DPB, in a murine model of DPB caused by P. aeruginosa. Mice were intubated with either P. aeruginosa- or saline-precoated tubes for 80 days. Thereafter, the expression of T-cell co-stimulatory molecules (CD40, CD80, and CD86) and cytokine secretion (interleukin (IL)-10, IL-6, IL-12p40, and tumor necrosis factor (TNF)-α) on bone marrow-derived DCs stimulated by lipopolysaccharide were examined by flow cytometry and enzyme-linked immunosorbent assays. The expression of co-stimulatory molecules was significantly decreased in mice infected with P. aeruginosa compared to the saline-treated control mice, but production of these cytokines did not significantly differ between the two groups. Pretreatment with clarithromycin ex vivo decreased CD40 expression on DCs obtained from P. aeruginosa-infected mice and also decreased the production of IL-6, IL-12p40 and TNF-α by DCs. These findings suggest that chronic P. aeruginosa infection alters DC functions and that macrolides function as anti-inflammatory agents by modulating the functions of DCs in chronic P. aeruginosa infection.View full abstractDownload PDF (659K) -
Sawako Takeuchi, Akira Matsuo, Hiroshige Chiba2010 Volume 220 Issue 1 Pages 67-75
Published: 2010
Released on J-STAGE: December 29, 2009
JOURNAL FREE ACCESSDistraction osteogenesis (DO) is a surgical process of new bone generation through the gradual extension of two segments of existing bone. DO is applied for maxillofacial surgeries to manage defects in mandibular continuity. Vertical DO with an oral device is often employed to augment the alveolar bone height for better implant anchorage for esthetic purposes or functional prosthetic requirements. To determine how the periosteum affects the vertical DO in mandibular reconstruction, we extracted the teeth and resected the alveolar parts of the mandible on both sides of dogs, along with removal of the surrounding periosteum in the right, but not left side. Three months later, box-shaped bone segments (vectors) were prepared from the resected alveolar part, and the segments were vertically elongated using a distraction device on both sides at 0.9 mm/day for one week. The extent of bone formation after distraction was determined with micro-focused computed tomography and by measuring incorporation of tetracycline and calcein with confocal laser scanning microscopy. During the initial two months after distraction, new bone formation was observed more prominently in the left side than in the right side of mandible with the periosteum. However, this difference was less clear during the bone-remodeling period. One notable change was the reduced height of the alveolar part of the right-side mandible, a sign of external bone resorption, observed in two out of three dogs at 6-month post-consolidation. These findings suggest that preservation of periosteum prevents the external bone resorption during the vertical DO of mandible.View full abstractDownload PDF (3606K) -
Ning Wang, Hui Zhao, Weitian Han, Bin He, Shucheng Zhang, Jiedong Wang2010 Volume 220 Issue 1 Pages 77-82
Published: 2010
Released on J-STAGE: December 29, 2009
JOURNAL FREE ACCESSMifepristone is a synthetic steroid compound that has been applied to terminate early pregnancy for many years. However, about 15% of the women undergo failure in termination of early pregnancy, the causes of which remain largely unknown. We herein selected estrogen receptor 1 gene (ESR1) as a candidate gene to determine whether single nuclear polymorphisms (SNPs) in ESR1 were associated with the failure of mifepristone-induce abortion. The subjects recruited were 30 subjects that failed to abort and 60 subjects with a successful medical abortion. Three SNPs, T-397C (rs2234693), C325G (rs1801132), and G2014A (rs2228480), were analyzed by PCR, followed by restriction fragment length polymorphism (RFLP) analysis. The latter two polymorphic sites are located in the protein-coding region, but do not alter the amino acid. Among the three SNPs examined, we found the significant role of the G2014A polymorphism; namely, the distribution of the GG, AG and AA genotypes was different between the failure group and the success group. The frequency of the GG (G2014G) genotype was higher in the failure group (86.7%) than that in the success group (60.0%) (p = 0.030), while the frequency of the G2014A heterozygote was lower in the failure group (6.7%) than in the success group (28.3%) (p = 0.013). Moreover, the frequency of the G allele was higher in the failure group (90%) and lower in the success group (10.0%) (p = 0.013). These results indicate that the GG genotype of the G2014A polymorphism is associated with the risk of failure in the mifepristone-induced abortion.View full abstractDownload PDF (287K) -
Kazuhiro Yoshimitsu, Naoto Shiba, Hiroo Matsuse, Yoshio Takano, Tohoru ...2010 Volume 220 Issue 1 Pages 83-93
Published: 2010
Released on J-STAGE: December 29, 2009
JOURNAL FREE ACCESSExtreme skeletal muscle atrophy is rampant in astronauts exposed to extended periods of microgravity (μG), and it is one of the main problems in human space exploration. A “Hybrid training” (HYB) method utilizing combined electrical stimulation and voluntary muscle contraction has been developed as a possible solution. A wearable HYB device and a virtual reality (VR) system were developed for use in space, and were verified at μG generated by parabolic flight (PF). A 36-year-old male subject performed HYB of reciprocal flexion and extension as a knee joint exercise training in a seated position at 1G, 2G and μG. The wearable HYB device and VR system developed for the study functioned well during the flight. However knee extension was insufficient at 1G and 2G, and the maximum knee extension angles at 1G and 2G were smaller than at μG. The extension velocity in the latter half of each motion was slower than in the first half at 1G and 2G, but no difference in velocity was observed at μG. The subject could extend the knee joint sufficiently and keep a constant extension velocity, because his legs were weightless at μG. The congruity between the subject's actual joint motions and instructed joint motions during μG was improved, when VR was employed with or without body fixation; accordingly, the subject was able to perform the desired joint motion. The VR system improved HYB exercise performance at μG during PF. HYB is considered a useful training method for future human space exploration.View full abstractDownload PDF (875K)
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