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Shohei Kuniya,1 Yusuke Miyazawa,1 Ryuichi Sawa,2 Tamaki Nara,1,3 Shuko Nojiri,1,3 Tsuyoshi Asai,4 Kanako K Kumamaru,1,3,5 Morikuni Tobita1,3 1Department of Healthcare Innovation, Juntendo University Graduate School of Medicine, Tokyo, Japan; 2Department of Physical Therapy, Faculty of Health Science, Juntendo University, Tokyo, Japan; 3Medical Technology Innovation Center, Juntendo University, Tokyo, Japan; 4Faculty of Rehabilitation, Kansai Medical University, Osaka, Japan; 5Department of Radiology, Juntendo University, Tokyo, JapanCorrespondence: Morikuni Tobita, Medical Technology Innovation Center, Juntendo University, 2-1-1 hongo, Bunkyo, Tokyo, 1138421, Japan, Tel +81-3-3814-5672, Fax +81-3-5802-1715, Email mtobita@juntendo.ac.jpPurpose: As the number of older adults in society increases, their social roles and networks, as well as their physical function, decrease. This study aimed to clarify the association between social networks and physical function among people aged ≥ 60 years in rural Thailand.Patients and Methods: This cross-sectional study was conducted in the Photharam District, Ratchaburi Province, Thailand. Participants were required to be at least 60 years old and be able to walk to the health center. Social networks were surveyed using the Thai version of Lubben Social Network Scores-6. Four physical function measures, namely hand grip strength, five-times-sit-to-stand test, timed up-and-go (TUG) test, and one-leg standing, were considered. Regression analysis was conducted with Lubben Social Network Scores-6 as the dependent variable and the four types of physical function as independent variables.Results: A total of 497 older adults aged 60 years or more were enrolled; 82 were males, and 412 were females. The mean Lubben Social Network Scores-6 was 14.9 ± 5.7. Only the TUG test was associated in a single and multiple regression analysis with the Lubben Social Network Scores-6 as the dependent variable and the four physical function assessments as independent variables.Conclusion: The TUG test assessed the smoothness of normal standing and walking, which are essential physical functions for maintaining a social network and meeting people. This suggests a relationship between physical function and social network.Keywords: Lubben Social Network Scores-6, social relationship, timed up-and-go test, aging

Yoshihiro Fukumoto,1,2 Tome Ikezoe,2 Masashi Taniguchi,2 Yosuke Yamada,3 Shinichiro Sawano,4 Seigo Minani,5 Tsuyoshi Asai,6 Misaka Kimura,7,8 Noriaki Ichihashi2 1Department of Physical Medicine and Rehabilitation, Kansai Medical University, Hirakata, Japan; 2Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 3National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan; 4Rehabilitation Units, Shiga University of Medical Science Hospital, Otsu, Japan; 5Faculty of Rehabilitation, Osaka Kawasaki Rehabilitation University, Kaizuka, Japan; 6Faculty of Rehabilitation, Kobe Gakuin University, Kobe, Japan; 7Institute for Active Health, Kyoto University of Advanced Science, Kameoka, Japan; 8Graduate School of Nursing, Doshisha Women’s College of Liberal Arts, Kyotanabe, JapanCorrespondence: Yoshihiro FukumotoDepartment of Physical Medicine and Rehabilitation, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata City, Osaka, Osaka, JapanTel +81-72-856-2307Fax +81-72-856-2150Email fukumoty@hirakata.kmu.ac.jpPurpose: Ultrasound-based prediction methods for the detection of low muscle mass for sarcopenia in older adults have been explored previously; however, the muscle that most accurately predicts it is unclear. This study aimed to clarify prediction accuracy and cut-off values for ultrasound-derived thigh and lower leg muscle thickness (MT) to detect low skeletal muscle mass index (SMI) in older adults and to estimate cut-off values based on two standard deviations (SD) below younger adult means for the corresponding muscles as an early detection tool for site-specific low muscle mass.Methods: This study included 204 community-dwelling older (64 males, 140 females, mean age: 75.4 years) and 59 younger (31 males, 28 females, mean age: 22.3 years) adults. The MT of the rectus femoris, vastus intermedius, gastrocnemius, and soleus muscles was measured using ultrasound; SMI was measured using bioelectrical impedance analysis.Results: The prevalence of a low SMI among older adults was 20.3% (n=13) for males and 21.4% (n=30) for females. The receiver operating characteristic analysis revealed that the total MT for the four muscles measured presented the highest area under the curve (AUC) value to predict low SMI for males (0.849) and females (0.776). The AUC value was the highest for the total MT of the gastrocnemius and soleus muscles for males and the gastrocnemius for females (0.836, 0.748; cut-off value: 5.67 cm, 1.42 cm, respectively). Muscle-specific differences between the low SMI-predicting and SD-based cut-off values were observed. The SD-based value for the rectus femoris (1.85 cm) was substantially higher than the low SMI-predicting value (1.51 cm) in males.Conclusion: Ultrasound measurement of lower leg muscles may be a simple, robust measure to detect low muscle mass for sarcopenia. Additionally, cut-off values for site-specific muscle mass loss may not always agree with those for whole-limb muscle mass loss.Keywords: area under the curve, bioelectric impedance, skeletal muscle, ultrasound

We have previously constructed an antibody-avidin (Av) fusion protein, anti-transferrin receptor (TfR) IgG3-Av, which can deliver biotinylated molecules to cells expressing the TfR. We now describe the use of the fusion protein for antibody-directed enzyme prodrug therapy (ADEPT). The 67 amino acid carboxyl-terminal domain (P67) of human propionyl-CoA carboxylase a subunit can be metabolically biotinylated at a fixed lysine residue. We genetically fused P67 to the carboxyl terminus of the yeast enzyme FCU1, a derivative of cytosine deaminase that can convert the non-toxic prodrug 5-fluorocytosine to the cytotoxic agent 5-fluorouracil. When produced in Escherichia coli cells overexpressing a biotin protein ligase, the FCU1-P67 fusion protein was efficiently mono-biotinylated. In the presence of 5-fluorocytosine, the biotinylated fusion protein conjugated to anti-rat TfR IgG3-Av efficiently killed rat Y3-Ag1.2.3 myeloma cells in vitro, while the same protein conjugated to an irrelevant (anti-dansyl) antibody fused to Av showed no cytotoxic effect. Efficient tumor cell killing was also observed when E. coli purine nucleoside phosphorylase was similarly targeted to the tumor cells in the presence of the prodrug 2-fluoro-2'-deoxyadenosine. These results suggest that when combined with P67-based biotinylation, anti-TfR IgG3-Av could serve as a universal delivery vector for targeted chemotherapy of cancer. (c) 2004 Elsevier B.V. All rights reserved.

Author(s): K. Hirota [sup.1], M. Yamakage [sup.2], S. Hashimoto [sup.3], T. Asai [sup.4], S. Isono [sup.5] Author Affiliations: (1) 0000 0001 0673 6172, grid.257016.7, Department of Anesthesiology, Hirosaki University Graduate [...], Respiratory management during general anesthesia aims to safely secure the airway and maintain adequate ventilation to deliver oxygen to the vital organs, maintaining homeostasis even during surgery. Despite its clinical importance, anesthesiologists often encounter difficulties in properly managing respiration during the perioperative period, leading to severe respiratory complications. In this year's JA symposium, 5 editorial board members of Journal of Anesthesia (JA) who are experts in the field of respiratory management in anesthesia discussed the following topics: quitting smoking before surgery: exposure to passive smoke is damaging to children, ventilator-associated pneumonia, high inspiratory oxygen concentration and lung injury, aspiration pneumonia, and postoperative respiratory management strategy in patients with obstructive sleep apnea. We hope that this special article regarding this year's JA symposium may be useful for JA readers to manage clinical anesthesia on a daily basis.

Yasushi Ikuno, Satoko Fujimoto, Yukari Jo, Tomoko Asai, Kohji NishidaDepartment of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, JapanPurpose: To investigate the rate of choroidal thinning in highly myopic eyes.Patients and methods: A retrospective observational study of 37 eyes of 26 subjects (nine males and 17 females, mean age 39.6 ± 7.7 years) with high myopia but no pathologies who had undergone spectral domain optical coherence tomography and repeated the test 1 year later (1 ± 0.25 year) at Osaka University Hospital, Osaka, Japan. Patients older than 50 years with visual acuity worse than 20/40 or with whitish chorioretinal atrophy involving the macula were excluded. Two masked raters measured the choroidal thicknesses (CTs) at the foveda, 3 mm superiorly, inferiorly, temporally, and nasally on the images and averaged the values. The second examination was about 365 days after the baseline examination. The CT reduction per year (CTRPY) was defined as (CT 1 year after - baseline CT)/days between the two examinations × 365. The retinal thicknesses were also investigated.Results: The CTRPY at the fovea was −1.0 ± 22.0 µm (range –50.2 to 98.5) at the fovea, –6.5 ± 24.3 µm (range −65.8 to 90.2) temporally, –0.5 ± 22.3 µm (range –27.1 to 82.5) nasally, –9.7 ± 21.7 µm (range –40.1 to 60.1) superiorly, and –1.4 ± 25.5 µm (range –85.6 to 75.2) inferiorly. There were no significant differences in the CTRPY at each location (P = 0.34). The CT decreased significantly (P < 0.05) only superiorly. The superior CTRPY was negatively correlated with the axial length (P < 0.05). The retinal thickness at the fovea did not change. Stepwise analysis for CTRPY selected axial length (P = 0.04, R2 = 0.13) and age (P = 0.08, R2 = 0.21) as relevant factors.Conclusions: The highly myopic choroid might gradually thin and be affected by many factors. Location and axial length are key factors to regulate the rate of choroidal thinning in highly myopic eyes. Overall choroidal thickness was not found to change significantly. Longer follow-ups are needed.Keywords: high myopia, choroid, optical coherence tomography, age

Miki Honda,1 Tomohiro Asai,2 Naoto Oku,2 Yoshihiko Araki,3 Minoru Tanaka,1 Nobuyuki Ebihara11Department of Ophthalmology, Juntendo University Urayasu Hospital, Chiba, Japan; 2Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan; 3Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, JapanAbstract: Poor drug delivery to lesions in patients' eyes is a major obstacle to the treatment of ocular diseases. The accessibility of these areas to drugs is highly restricted by the presence of barriers, including the corneal barrier, aqueous barrier, and the inner and outer blood–retinal barriers. In particular, the posterior segment is difficult to reach for drugs because of its structural peculiarities. This review discusses various barriers to drug delivery and provides comprehensive information for designing nanoparticle-mediated drug delivery systems for the treatment of ocular diseases. Nanoparticles can be designed to improve penetration, controlled release, and drug targeting. As highlighted in this review, the therapeutic efficacy of drugs in ocular diseases has been reported to be enhanced by the use of nanoparticles such as liposomes, micro/nanospheres, microemulsions, and dendrimers. Our recent data show that intravitreal injection of targeted liposomes encapsulating an angiogenesis inhibitor caused significantly greater suppression of choroidal neovascularization than did the injection of free drug. Recent progress in ocular drug delivery systems research has provided new insights into drug development, and the use of nanoparticles for drug delivery is thus a promising approach for advanced therapy of ocular diseases.Keywords: intravitreal injection, drug delivery system, age-related macular degeneration, APRPG-modified PEGylated liposome, DDS