Invited Review Article
Pro-Addictive and Anti-Addictive Factors for Drug Dependence
KIYOFUMI YAMADA
pg(s) 67- 72
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Drug dependence is defined as a chronically relapsing disorder that is characterized by compulsive drug taking, inability to limit intake, and intense drug cravings. The positive reinforcing/rewarding effects of drugs primarily depend on the mesocorticolimbic dopamine system innervating the nucleus accumbens while the craving for drugs is associated with activation of the prefrontal cortex. The chronic intake of drugs causes homeostatic molecular and functional changes in synapses, which may be critically associated with the development of drug dependence. Recent studies have demonstrated that various cytokines and proteinases are produced in the brain on treatment with drugs of abuse, and play a role in drug dependence. These endogenous modulators of drug dependence are divided into two groups, pro-addictive and anti-addictive factors. The former including tissue plasminogen activator, matrix metalloproteinase (MMP)-2 and MMP-9 act to potentiate the rewarding effects of drugs, while the latter such as tumor necrosis factor-a and glial cell line-derived neurotrophic factor reduce the reward. These findings suggest that an imbalance between pro-addictive and anti-addictive factors contributes to the development and relapse of drug dependence. Targeting these endogenous modulators would provide new therapeutic approaches to the treatment of drug dependence.
Original Papers
Expression and Roles of a Xenopus Head-Forming Gene Homologue in Human Cancer Cell Lines
YINGSONG ZHU, AKIKO TSUCHIDA, AKIHITO YAMAMOTO, KEIKO FURUKAWA, ORIE TAJIMA, NORIYO TOKUDA, SHINICHI AIZAWA, TAKESHI URANO, KENJI KADOMATSU and KOICHI FURUKAWA
pg(s) 73- 82
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Molecular mechanisms for both morphogenesis and carcinogenesis have frequently overlapped, and similar signaling pathways are often involved in these processes. Yamamoto et al. identified a novel protein that induces head formation in Xenopus (Yamamoto et al. Cell, 120, 223-225, 2005). This new protein, named Shisa, plays unique roles in head formation by suppressing the maturation processes of receptors for Wnt and FGF at the endoplasmic reticulum. Here, we have identified a human homologue of the shisa gene (hu-shisa-2), and analyzed its expression in various human cancer cell lines by real-time reverse transcription polymerase chain reaction. High levels of mRNA expression were observed in some neuroectoderm-derived human cancer cell lines and small cell lung cancer cell lines. Intracellular localization of hu-Shisa-2 protein was also analyzed, indicating that it is present in the endoplasmic reticulum. Over-expression of hu-Shisa-2 resulted in increased cell growth and invasion, suggesting that hu-Shisa-2 is involved in the evolution and/or progression of human cancers.
Comparison of Sleep-Disordered Breathing and Heart Rate Variability between Hemodialysis and Non-Hemodialysis Days in Hemodialysis Patients
MAYO SUKEGAWA, AKIKO NODA, TARO SOGA, YUKI ADACHI, YOSHINARI TSURUTA, NORIO OZAKI and YASUO KOIKE
pg(s) 83- 88
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Sleep disturbances manifesting as insomnia, daytime sleepiness, fatigue, and other symptoms are frequently found in patients with end-stage renal disease that is being treated with dialysis. Many factors, including neurosis, uremic symptoms, dialysis drugs, and sleep-wake rhythms have been suggested as potential causes for these sleep disturbances. We examined sleep apnea/hypopnea and heart rate variability (HRV) reflecting autonomic activity in hemodialysis patients on their hemodialysis and non-hemodialysis days using a home medical care device (Morpheus C, TEIJIN). Eleven hemodialysis patients and 14 healthy adults were enrolled in this study. We calculated the number of apnea/hypopnea episodes per hour (apnea/hypopnea index: AHI) and HRV (percentage of R-R intervals that differ by at least 50 ms from the previous interval: pNN50, very low frequency: VLF, low frequency: LF, high frequency: HF and LF/ HF). There was no significant difference in the AHI between hemodialysis and non-hemodialysis days. The heart rate in hemodialysis patients on non-hemodialysis days was significantly higher than in the controls, whereas the pNN50 was significantly lower in hemodialysis patients on non-hemodialysis days than in the controls. Although VLF was significantly lower in hemodialysis patients on non-hemodialysis days compared to the controls, there were no significant differences in LF, HF or LF/HF between the two groups. Hemodialysis itself might not be an important contributing factor in sleep-related breathing disturbances. The simultaneous analysis of HRV reflecting autonomic activity and sleep-disordered breathing on both hemodialysis and non-hemodialysis days provides important information.
Development and Validity of the Japanese Version of Body Shape Silhouette: Relationship between Self-Rating Silhouette and Measured Body Mass Index
KEN NAGASAKA, KOJI TAMAKOSHI, KUNIHIRO MATSUSHITA, HIDEAKI TOYOSHIMA and HIROSHI YATSUYA
pg(s) 89- 96
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We devised new body shape silhouettes to more accurately reflect Japanese body sizes. Our aim was to assess the association between measured body mass index (BMI) and body size through self-selection of nine figure scales. This study was comprised of 4808 men and 1093 women aged 35–71 years. Subjects were asked to identify the silhouettes that most accurately represent their current body size. BMI was calculated from measured height and weight based on annual health checkups. Spearman’s correlation coefficients between silhouette ratings and BMI were 0.73 in men and 0.80 in women. Moreover, mean BMIs increased in value with increasing silhouette numbers in both genders (trend p < 0.01 for both). Simple linear regression models predicting BMI based on silhouette ratings showed a good fit, with silhouette self-selection statistically explaining 54.0% of BMI variance in men and 62.5% in women. Receiver operating curves showed that areas under the characteristics curves were higher than 0.8 for obesity and thinness in both genders. These findings suggest that our scale is a promising tool for examining body size and image among Japanese adults.
Evaluation of Cetirizine Hydrochloride-Based Therapeutic Strategy for Chronic Urticaria
KAZUMITSU SUGIURA, SATOKO HIRAI, TAMIO SUZUKI, TOSHIKAZU USUDA, TAKAO KONDO, TERUO AZUMI, SADAO MASAKI, TAKAOMI YOKOI, YUKIKO NITTA, SHIGERI KAMIYA, KOICHI ANDO, TAKAKO MORI and YASUSHI TOMITA
pg(s)97-106
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We investigated the suitability of cetirizine HCl (cetirizine) for the initial treatment of chronic urticaria. A secondary aim was to identify the optimal alternative treatments when switching from this drug to other drugs in patients who are dissatisfied with cetirizine. We started cetirizine at a once-daily dose of 10 mg for 2 weeks and then, depending on the course of symptoms in individual patients, it was either continued, titrated to a higher dose, or switched to other drugs (antihistamines including H2 blockers) for a further 2 weeks. Degrees of patient satisfaction and ratings by physicians were analyzed, as were adverse events. At 2 weeks after the start of treatment, among 74 patients included in the final evaluation 55 (74.3%) expressed satisfaction with cetirizine therapy. Those not satisfied included five (6.7%) who felt drowsy after taking the drug and 14 (18.9%) in whom the drug had not demonstrated adequate efficacy. After optimizing the treatment on a per-patient basis, including switching from cetirizine to other drugs, the percentage satisfied with treatment at 4 weeks was 83.7% (62/74). In the group of patients who were satisfied with the therapy at 2 weeks, attending physicians confirmed that wheals and scratches were significantly alleviated at 2 and 4 weeks, respectively. Adverse effects were mild and uncommon. Cetirizine as an initial treatment for chronic urticaria appears effective and safe. For patients in whom cetirizine fails to satisfactorily alleviate symptoms as well as those who complain of drowsiness, switching to other antihistamine drugs may be an effective strategy.
Controls for Monitoring the Deterioration of Stored Blood Samples in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study)
MARIKO NAITO, HIDETAKA EGUCHI, RIEKO OKADA, YOSHIKO ISHIDA, KAZUKO NISHIO, ASAHI HISHIDA, KENJI WAKAI, AKIKO TAMAKOSHI and NOBUYUKI HAMAJIMA for the J-MICC Study Group
pg(s)107-115
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Cohort studies commonly store blood samples to measure the associations of biomarkers with disease risks for a long time after the study subjects are enrolled. To obtain valid measurements of the stored samples, monitoring their degree of deterioration is essential. The first stage of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study launched in 2005 included a project to validate the quality of stored blood samples. This project will compare the measurements of representative molecules over different storage periods (1, 4, and 8 years after sampling, and when a nested case-control study is conducted), different storage temperatures (–80 and –150°C), and different separation conditions (temperature and time) before storage. For these purposes, 28 ml of peripheral blood from 10 people was sampled four times annually, using two tubes for serum and two EDTA -Na tubes for plasma. These samples were treated using the process adopted for the J-MICC study protocol, and stored in tubes containing 300 μl of serum or plasma labeled with two-dimensional bar codes. The sampling was started in 2006, and some of the specimens will be stored until the end of the J-MICC Study in 2035. The resulting findings will produce valuable information on the stability of the molecules, not only for the J-MICC Study, but also for other cohort studies.
Skeletel Muscle Syntrophin Interactors Revealed by Yeast Two-Hybrid Assay
MASAHIKO INOUE, YOSHIHIRO WAKAYAMA, TAKAHIRO JIMI, SEIJI SHIBUYA, HAJIME HARA, AKIHIKO UNAKI and KIYOKAZU KENMOCHI
pg(s)117-126
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Syntrophins are the cytoplasmic peripheral proteins of dystrophin glycoprotein complex, of which five (α1, β1, β2, γ1 and γ2) isoforms have been identified so far. Respective syntrophin isoforms are encoded by different genes but have similar domain structures. At the sarcolemma of skeletal muscle, the most abundant α1-syntrophin was shown to interact at its PDZ domain with many membrane proteins. Among them, the AQP4 interaction with α1-syntrophin PDZ domain was demonstrated by a Tg mouse study, prompting us to investigate the interaction between mouse α1-syntrophin (BC018546: nt.267–492, PDZ domain) pEXP-AD502 as prey vector and mouse AQP4 (NM009700: nt.805–969) pDBLeu as bait vector by the yeast two-hybrid assay, resulting in a negative study. We further studied the binding partner of another sarcolemma located β1-syntrophin, and performed a yeast two-hybrid experiment. With human β1-syntrophin as bait and human skeletal muscle cDNA library as prey, we obtained one positive clone which turned out to be α-dystrobrevin. Although the interaction of human β1-syntrophin with α-dystrobrevin has already been shown by immunoprecipitation assay, we have here confirmed this interaction by a yeast two-hybrid experiment.
Short Communication
Intraosseous Glomus Tumor of the Ulna: a Case Report with Radiographic Findings and a Review of the Literature
HIROSHI URAKAWA, HIROATSU NAKASHIMA, YOSHIHISA YAMADA, MIKITO TSUSHIMA, TAKEHIRO OHTA and TOMOKO NISHIO
pg(s)127-133
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Intraosseous glomus tumors of bone are extremely rare. We report a case of an intraosseous glomus tumor of the ulna. The patient was a 25-year-old woman who had a three-month history of a palpable mass in her right forearm with spontaneous pain. Radiographs showed cortical hypertrophy and a shelllike bone formation surrounding the small osteolytic lesion within the cortex of the ulna diaphysis. The differential diagnosis included benign bone-forming tumors, such as osteoid osteoma. The patient was treated with an en-bloc resection and filling with beta-TCP. Up to one year after the operation there has been no evidence of recurrence.
