著者

Masatoshi OKUBO Yoh-ichi SATOH Masato HIRAKAWA Kana SASAKI Kazuki MASU Gabriel J. MCHONDE Chika IKEDA-KUROSAWA Daijiro KUROSAKA Tomoyuki SAINO

出版者

Biomedical Research Press

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.37, no.2, pp.101-115, 2016-04-01 (Released:2016-04-23)

参考文献数

87

被引用文献数

3 3

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5-hydroxytriptamine (5-HT: serotonin) is an important transmitter that causes vessel constriction, although few studies have examined the effect of 5-HT on venous smooth muscles. The intracellular Ca2+ concentration ([Ca2+]i) plays an essential role in stimulus-response coupling in numerous tissue/cells including vascular smooth muscle cells. The present study was performed to examine whether differences between arteries and veins in the response to 5-HT can be detected under confocal microscope with respect to [Ca2+]i dynamics. In posterior ciliary arteries of rats, 5-HT induced a [Ca2+]i increase. The 5-HT-induced responses were caused by both Ca2+ influx and mobilization. Agonist and antagonist experiments revealed that arterial smooth muscles possess 5-HT1a, 1b, 2 (Gprotein-coupled type) and 5-HT3 (ion channel type) receptors, and that 5-HT2 in particular plays a major role in these responses. For vorticose veins, the 5-HT-induced responses were also caused by both Ca2+ influx and mobilization. However, the cAMP dependent pathway (5-HT4-7) was found to be significant in vasocontraction with respect to 5-HT in these vessels. Thus, Ca2+ mobilization was induced by 5-HT2 and 5-HT4-7 in a vessel-dependent manner, whereas Ca2+ influx universally was induced by 5-HT3. These results indicate that the posterior ciliary arteries and vorticose veins in the same tissue might differ greatly in their responses to stimulus.

著者

Yuuki HORII Kanako OKADERA Shingo MIYAWAKI Takahiko SHIINA Yasutake SHIMIZU

出版者

Biomedical Research Press

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.43, no.2, pp.53-57, 2022-04-15 (Released:2022-04-15)

参考文献数

27

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Torpor, a state of lowered body temperature due to active reduction of the metabolic rate, has potential medical benefits. The aim of this study was to establish a novel laboratory animal that enter torpor without imposing complex conditions. When house musk shrews (Suncus murinus) were kept at an ambient temperature of 24°C, most of the animals did not enter daily torpor. However, when the ambient temperature was lowered to below 20°C, all of the shrews showed torpor in the absence of fasting and short-day photoperiod. The shrews that were exposed to a stepwise decrease in ambient temperature from 24°C to 8°C entered torpor even after returning them to a room kept at 24°C. In conclusion, this study indicates that Suncus murinus may be a suitable model animal for elucidating the mechanism of daily torpor. Elucidation of the mechanisms of torpor by using this model may be useful for inducing a state of artificial hibernation in various species including humans.

著者

Keiko Nakazato Yuko Yoshida Ken Takemori Katsuya Kobayashi Atsuhiro Sakamoto

出版者

Biomedical Research Press

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.30, no.1, pp.17-24, 2009 (Released:2009-03-06)

参考文献数

38

被引用文献数

10 13

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We previously showed that sevoflurane anesthesia affected the expression ratios of 177 of 10,000 genes in multiple organs of rats by microarray analyses. The maximum number of altered genes was detected in the liver, and included several genes characterized as encoding drug-metabolizing enzymes (DMEs). Here, we investigated whether alterations of pharmacokinetic gene expressions after anesthesia differed between inhalation and intravenous anesthesia, and how long the alterations persisted after awakening from anesthesia. Livers were obtained from rats (n = 6 per group) anesthetized with sevoflurane, isoflurane, propofol or dexmedetomidine for 0 or 6 h, and rats awakened for 24 h after anesthesia for 6 h. The mRNA expression ratios of eight genes encoding DMEs that showed the greatest alterations in the previous study, namely Cyp7a1, Cyp2b15, Por, Nr1i2, Ces2, Ugt1a7, Abcb1a and Abcc2, were measured by quantitative real-time reverse transcriptase-polymerase chain reaction. The expression ratios were mostly increased after 6 h of anesthesia and returned to their control levels at 24 h after awakening from anesthesia. However, the expression ratios of some genes remained elevated for 24 h after awakening from anesthesia. There were differences between inhalation and intravenous anesthesia, and interestingly, between sevoflurane and isoflurane and between propofol and dexmedetomidine.

著者

Chikako TOMIYAMA Mayumi WATANABE Takashi HONMA Akihiro INADA Takayoshi HAYAKAWA Masae RYUFUKU Toru ABO

出版者

Biomedical Research Press

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.36, no.2, pp.135-142, 2015-04-01 (Released:2015-04-16)

参考文献数

31

被引用文献数

12 19

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The effect of repetitive mild hyperthermia on body temperature, the autonomic nervous system, and innate and adaptive immunity was investigated using a new hyperthermia treatment system, nanomist sauna (NMS). Six healthy volunteers participated and the concentration of catecholamines and cortisol, and the frequency and function of leukocytes in the peripheral blood were investigated before and after successive 7 days of hyperthermia treatment (20 min/day, 40°C, 100% relative humidity). After treatment, the blood level of adrenaline and cortisol on the 7th day was decreased compared with the 1st day, indicating the suppression of the sympathetic nervous system activity. Moreover, the frequency of CD56+NK, CD56+NKT and B cells on the 7th day tended to be increased compared with the 1st day. The frequency of HLA-DR-positive NK and NKT cells and expression of HLA-DR on B and T cells increased. The cytotoxicity of NK cells and proliferative response of B cells were also elevated. The results indicate that repetitive mild hyperthermia treatment might suppress excessive sympathetic dominance and modify immunity. Additionally, because it can provide the same effects as conventional hyperthermia treatments with minimal burden to the body, NMS may be a novel patient- and elderly-friendly hyperthermia treatment for health promotion.

著者

Takahiro INOUE Yasuyuki TAKAMATSU Misato OKAMURA Hiroki MANI Naoya HASEGAWA Hiroshi MAEJIMA

出版者

Biomedical Research Press

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.42, no.3, pp.103-108, 2021-06-07 (Released:2021-06-07)

参考文献数

18

被引用文献数

1

---

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system (CNS). This study examined the effect of specific inhibition of α5 subunit-containing GABAA receptors (α5GABAAR) on the behavioral profile and neuronal activity of the CNS using a compound called L-655,708, which is a selective negative allosteric modulator of α5GABAAR. L-655,708 administration significantly increased locomotor activity without anxiety-related behavior. Furthermore, L-655,708 administration significantly increased c-Fos mRNA expression (a neuronal activity marker) in motor area of the cerebral cortex, whereas it hardly altered c-Fos mRNA expression in the sensory cortex, hippocampus, and spinal cord. This study revealed for the first time that alteration of neuronal activity with specific inhibition of α5GABAAR differs depending on each CNS region. α5GABAAR could be a potential target for modulating CNS excitability and behavioral activity.

著者

JOAN D. BOOMSMA HUSSEIN D. FODA SAMI I. SAID

出版者

Biomedical Research Press

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.12, no.4, pp.273-277, 1991-08-01 (Released:2015-06-01)

被引用文献数

7 7

著者

Keishi HATA TOMATSU Sayaka Masaki TAKAHASHI Akira SASAKI Yui UMEKAWA Kazuya MIYASHITA Kazumi OGURA Gen TOSHIMA Masahiro MAEDA Junichiro TAKAHASHI Masakazu KAKUNI

出版者

Biomedical Research Press

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.41, no.1, pp.33-42, 2020-02-01 (Released:2020-02-22)

参考文献数

24

被引用文献数

5

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We investigated lipid metabolism in PXB-cells, which are human primary hepatocytes isolated from liver-humanized mice, and HepG2 and HuH-7 human hepatoma cell lines. Lipoprotein levels were higher in PXB-cells than in the 2 other cell lines, and PXB-cells mainly released triglycerides and cholesterol as very low density lipoprotein (VLDL), similar to actual liver tissue, whereas the major lipoprotein released from the 2 hepatoma cell lines was LDL. RT-PCR analysis demonstrated that the gene expression levels of apolipoprotein B100 (ApoB100), the apolipoprotein of VLDL/LDL, were similar in PXB-cells and HepG2 cells, while the overexpression of ApoC2, ApoC3, and ApoE, which are components of VLDL, but not LDL, was observed in PXBcells. A protein immunoassay revealed that ApoB100 levels secreted from PXB-cells and HuH-7 cells were similar; however, ApoC3 levels were higher in PXB-cells than in the two other cell lines. We also examined the anti-lipidemic activities of fenofibrate using this assay system. Fenofibrate suppressed lipoprotein production from PXB-cells in a dose-dependent manner mainly by activating the β-oxidation pathway. These results suggest that PXB-cells produce high levels of lipoproteins and are suitable for screening anti-lipidemic agents.

著者

Won Jae HUH Joseph TE ROLAND Masato ASAI Izumi KAJI

出版者

Biomedical Research Press

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.41, no.2, pp.113-118, 2020-04-01 (Released:2020-04-19)

参考文献数

19

被引用文献数

14

---

Clinical interest into the function of tuft cells in human intestine has increased in recent years. However, no quantitative study has examined intestinal tuft cells in pathological specimens from patients. This study quantified tuft cell density by using a recently identified marker, specific for tyrosine phosphorylation (pY1798) of girdin (also known as CCDC88A or GIV) in the duodenum of pediatric patients. Deidentified sections with pathological diagnosis of acute duodenitis, ulcer, or celiac disease, and age-matched normal control were analyzed under double-blind conditions. Immunostaining for pY1798-girdin demonstrated the distinct shape of tuft cells with and filopodia-like basolateral membrane structure and a small apical area, which densely expressed gamma-actin. As compared to normal tissues, the specimens diagnosed as celiac disease and duodenal ulcer had significantly fewer tuft cell numbers. In contrast, acute duodenitis showed varied population of tuft cells. The mucosa with severe inflammation showed lower tuft cell numbers than the specimens with none to mild inflammation. These results suggest that loss of tuft cells may be involved in prolonged inflammation in the duodenal mucosa and disrupted mucosal integrity. pY1798-girdin and gamma-actin are useful markers for investigating the distribution and morphologies of human intestinal tuft cells under healthy and pathological conditions.

著者

Hikaru TAKESHITA Eri WATANABE Yoshihiko NOROSE Yasuhiko ITO Hidemi TAKAHASHI

出版者

Biomedical Research Press

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.40, no.2, pp.87-95, 2019-04-01 (Released:2019-04-13)

参考文献数

22

被引用文献数

2

---

Helicobacter pylori (H. pylori) urease is a key protein for persistent infection of the bacteria in the stomach. Although H. pylori generally induce anti-H. pylori-specific antibodies (Abs), these Abs do not usually work for eradication or prevention of the H. pylori infection. In our previous study, we identified a linear epitope composed of 19-mer peptides termed UB-33, CHHLDKSIKEDVQFADSRI, within the large subunit of H. pylori urease. Anti-UB-33-specific Abs neutralized the enzymatic activity of H. pylori urease in vitro. In the present study, we evaluated the effect of immunization of BALB/c mice with H. pylori UB-33 peptide. After confirming the production of anti-UB-33-specific Abs, mice were challenged orally with H. pylori Sydney Strain-1 (SS-1). Mice producing anti-UB-33-specific Abs were not infected with SS-1, and the amount of SS-1 isolate in their stomach was significantly reduced. Also, the urease-negative mutant of H. pylori, HPP1801, did not colonize in the stomach, indicating that H. pylori urease was a critical element for infection of H. pylori in the gastric mucosa. Moreover, mice producing UB-33-specific Abs apparently suppressed H. pylori infection in the stomach where anti-UB-33 Abs were secreted in the gastric juice, indicating that H. pylori colonization was inhibited in the presence of anti-UB-33 Abs. In addition, the neutralization activity of sera from mice immunized with purified urease was less potent than that in the sera from mice immunized with UB-33. Furthermore, the recognition of epitope UB-33 was mediated through Toll-like receptor 2 (TLR2) on the B-1 cells using TLR2-knockout BALB/c mice in vivo. These results indicate that liner peptide UB-33 should be used for immunization to induce neutralizing Abs instead of purified H. pylori urease to prevent H. pylori infection and their colonization in the stomach.

著者

Kakeru ITO Miho YASUDA Yuki MAEDA Jean-Michel FUSTIN Yoshiaki YAMAGUCHI Yuka KONO Hiromitsu NEGORO Akihiro KANEMATSU Osamu OGAWA Masao DOI Hitoshi OKAMURA

出版者

Biomedical Research Press

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.39, no.2, pp.57-63, 2018-04-01 (Released:2018-04-18)

参考文献数

29

---

Micturition behavior follows regular day/night fluctuations, and unwanted increase in micturition could occur during night in jet lag condition. To clarify the effect of jet lag on micturition behavior, we simultaneously detected circadian micturition patterns and locomotor activity rhythms of mice under experimental jet lag conditions, by applying the improved automated Voided Stain on Paper (aVSOP) method. When wild-type (WT) mice were phase-advanced for 8 hours, day-night variation of micturition was disrupted suddenly, and this irregular daily micturition continued until 8 days, although their activity rhythms entrained gradually day by day until 8 days. We also examined how jet lag induced changes of micturition in Per-null mice lacking Per1, Per2 and Per3 genes, whose endogenous clock is completely disrupted. We found both micturition and locomotor activity of Per-null mice promptly entrained to the new LD cycle. These findings suggest that the irregular micturition during jet lag is caused along with the gradual shift of the endogenous clock, and paradoxically, jet lag-associated abnormality was absent when endogenous circadian oscillations were genetically disrupted.

著者

Masahiro TODA Shinsuke KUSAKABE Shingo NAGASAWA Kazuyuki KITAMURA Kanehisa MORIMOTO

出版者

Biomedical Research Press

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.28, no.2, pp.115-118, 2007 (Released:2007-05-16)

参考文献数

19

被引用文献数

17 31

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We investigated the effect of laughter on salivary endocrinological stress marker chromogranin A (CgA). In saliva samples collected from 11 healthy males before and after watching a comic film or a non-humorous control film, salivary CgA levels were determined by enzyme-linked immunosorbent assay (ELISA). Samples taken after watching the comic film showed increased levels of CgA. This tendency was more pronounced in individuals with lower initial levels of stress. The control samples showed no significant change in CgA levels. Stress score, subjectively evaluated using a visual analog scale, decreased significantly after watching the comic film. These findings suggest that, in addition to a stress relief effect, laughter can bring about feeling uplifted or fulfilled.

著者

Nobuhito IKEDA Natsumi NAKAZAWA Yasutaka KURATA Hisako YAURA Fikri TAUFIQ Hiroyuki MINATO Akio YOSHIDA Haruaki NINOMIYA Yuji NAKAYAMA Masanari KUWABARA Yasuaki SHIRAYOSHI Ichiro HISATOME

出版者

バイオメディカルリサーチプレス

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.38, no.4, pp.229-238, 2017-08-01 (Released:2017-08-09)

参考文献数

24

被引用文献数

8

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Proepicardium (PE) cells generate cardiac fibroblasts, smooth muscle cells (SMCs) and endothelial cells that form coronary arteries. T-box18 (Tbx18) is a well-known marker of PE cells and epicardium. We examined whether Tbx18-positive cells differentiated from murine embryonic stem (ES) cells serve as PE progenitors to give rise to vascular SMCs and fibroblasts. To collect Tbx18-positive cells, we established Tbx18-EGFP knock-in mouse ES cells using the CRISPR/Cas9 system. We harvested the Tbx18-EGFP-positive cells on day 8, 10 and 14 after the initiation of differentiation; Tbx18 mRNA was enriched on day 8 to 14 and Snai2 mRNA was enriched on day 8 and 10, indicating successful collection of Tbx18-positive cells. Tbx18-EGFP-positive cells expressed the PE marker WT1 on day 8 and 10. They also expressed the SMC marker Acta2 and fibroblast markers Thy1 and Fsp1 on day 8 to 14, but did not express the endothelial cell marker PECAM or the cardiac cell marker CD166 or Myh7. In conclusion, Tbx18-positive cells represent a part of PE cells in the initial phase of differentiation and subsequently include SMCs as well as fibroblasts. These results indicate that Tbx18-positive cells serve as a PE progenitor to supply a variety of cells that contribute to the formation of coronary arteries.

著者

Keisuke TSUTSUI Masato KAKU Masahide MOTOKAWA Yuiko TOHMA Toshitsugu KAWATA Tadashi FUJITA Shinya KOHNO Junji OHTANI Kaoru TENJOH Mao NAKANO Hiroko KAMADA Kazuo TANNE

出版者

バイオメディカルリサーチプレス

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.28, no.1, pp.1-7, 2007 (Released:2007-03-13)

参考文献数

22

被引用文献数

29 59

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It has been reported that reduction of masticatory afferent stimulation might influence learning and memory function. In order to clarify the influences of reduced masticatory sensory input on spatial memory/learning ability and neuropathological changes, we conducted the Morris water maze experiment and investigated the number of hippocampal neurons in association with the differences in masticatory afferent stimuli from hard- and soft-diet feeding in mice. The water maze experiment showed no significant difference in learning ability between 180-day-old solid- and powderdiet groups. Meanwhile, the ability was significantly reduced in the 360-day-old powder-diet group as compared with the age-matched solid-diet group. The total number of pyramidal cells in the hippocampal CA1 and CA3 regions was significantly smaller in 360-day-old powder-diet group than in the remaining groups. These results demonstrate that reduction of masticatory afferent stimuli due to long-term soft-diet feeding may induce neuron loss in the hippocampus and reduced memory/learning ability.

著者

Yasuyuki Kudo Satoko Morohashi Kaori Takasugi Shinji Tsutsumi Hiroshi Ogasawara Norihiro Hanabata Tetsuro Yoshimura Fuyuki Sato Shinsaku Fukuda Hiroshi Kijima

出版者

Biomedical Research Press

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.32, no.2, pp.127-134, 2011 (Released:2011-05-03)

参考文献数

23

被引用文献数

3 5

---

Recent advances in endoscopic submucosal dissection (ESD) techniques contribute to endoscopic treatment of early gastric cancer (EGC). Recognition of chronic atrophic gastritis as the background is important for high-quality detection and diagnosis of EGC. But, relationships between EGC and atrophy of the background gastric mucosa caused by Helicobacter pylori are not well understood. The present study demonstrated histopathological phenotypes of EGC, as well as chronic atrophic gastritis as background mucosa of EGC. We evaluated mucosal heights, number of glands, and degree of intestinal metaplasia (IM) of the background gastric mucosa, using 81 cases of EGC resected by ESD. Gastric phenotype cancer cases showed IM of the background gastric mucosa less frequently, compared with intestinal phenotype cancer cases (score of IM, 1.15 vs. 1.65, P = 0.012). The average mucosal heights around EGC were lower in moderately to poorly differentiated adenocarcinoma cases than well differentiated adenocarcinoma cases (442.6 μm vs. 500.2 μm, P = 0.011). The mucosal atrophy indicated by average heights of background mucosa was low in the gastric phenotype cancer cases, compared with the intestinal phenotype cancercases (452.8 μm vs. 505.6 μm, P = 0.018). In the fundic gland area, the mucosal heights were low in the gastric phenotype cancer cases, compared with the intestinal phenotype cancer cases (413.2 μm vs. 495.5 μm, P = 0.015). Our results using EGC specimens indicated that gastric phenotype cancer and moderately to poorly differentiated adenocarcinoma had atrophic background mucosa with lower mucosal heights and less IM. The atrophic gastric mucosa with less IM is thought to play an important role in gastric carcinogenesis, especially tumoriogenesis of gastricphenotype cancer.

著者

Kazuhiko OCHIAI Toshina ISHIGURO-OONUMA Yasunaga YOSHIKAWA Chihiro UDAGAWA Yuiko KATO Masami WATANABE Makoto BONKOBARA Masami MORIMATSU Toshinori OMI

出版者

バイオメディカルリサーチプレス

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.36, no.2, pp.155-158, 2015-04-01 (Released:2015-04-16)

参考文献数

21

被引用文献数

2 13

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Mutations in the breast cancer susceptibility gene BRCA2 leading to the failure of interactions with the recombinase RAD51 are associated with an increased risk of cancer in humans. This interaction depends on the eight BRC repeat (BRC1–8) sequences in BRCA2. We previously reported that canine BRC3 has two polymorphisms (T1425P and K1435R) influencing the interaction with RAD51, and 1435R was identified in mammary tumor dog samples. In this study, we investigated the sequence variations of BRC3 and 4 in 236 dogs of five breeds. Allele frequencies of 1425P and 1435R were 0.063 and 0.314, respectively, and there was no other polymorphism in the sequenced region. A mammalian two-hybrid assay using BRC3–4 sequences demonstrated that 1425P allele reduced the binding strength with RAD51 but 1435R had no effect. These results may provide an insight into the functions of not only individual but also multiple BRC repeats of BRCA2 in dogs.

著者

Tetsuya KAWAKITA Fuminori KAWABATA Tomoko TSUJI Motoko KAWASHIMA Shigeto SHIMMURA Kazuo TSUBOTA

出版者

バイオメディカルリサーチプレス

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.34, no.5, pp.215-220, 2013 (Released:2013-11-02)

参考文献数

19

被引用文献数

2 36

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The purpose of this study was to evaluate the efficacy of fish oil supplementation added to usual dry eye treatment in dry eye subjects in a randomized controlled trial. Twenty-seven typical dry eye subjects were selected from 43 candidates by the diagnostic criterion for dry eye in this study. They were assigned to the randomized fish oil group (n = 15) or the placebo group (n = 12). Fish oil group ingested fish oil capsules containing eicosapentaenoic acid (EPA, 1245 mg/day) and docosahexaenoic acid (DHA, 540 mg/day) for 12 weeks. Placebo group ingested placebo capsules without EPA or DHA. A visual analog scale test estimating subjective symptoms, the Schirmer I test, tear film break-up time (BUT) measurement, fluorescein staining, and rose bengal staining were performed every 4 weeks during the 12-week supplementation period and 4-week washout period. The subjective symptom of “eye pain”, BUT, and changes in rose bengal staining score of the fish oil group were significantly improved after 8-12 weeks of supplementation and/or 4 weeks of washout, compared to those of the placebo group. These results suggest that fish oil supplementation added to usual care may be effective in the treatment of dry eye.

著者

Kazunari Sato Toshihiko Kawamura Satoshi Yamagiwa

出版者

バイオメディカルリサーチプレス

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.31, no.4, pp.259-262, 2010 (Released:2010-09-08)

参考文献数

21

被引用文献数

4 5

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Neuroadrenergic abnormalities, including a predominant activity of parasympathetic nerve and blunted hormone secretion, are recognized in the overweight patients. This study aimed to examine whether the “Senobi” breathing method, a stretch-breathing exercise that we have developed, could activate or recover sympathetic nervous system activity that leads to the loss of body weight. Forty pre-menopausal women, aged 40 to 50 years, participated in this study. Twenty were healthy and the other 20 were overweight (body mass index › 25 and body fat › 30%). Sympathetic nerve activity was assessed using equipment that analyzes cardiac-beat variation, and several urinary hormone levels were examined before and 30 min after performing the “Senobi” breathing exercise. The average proportion of sympathetic nerve among healthy women during daytime hours (10 : 00 AM to 12 : 00 PM) was 62.6% ± 2.6%. On the other hand, that of overweight women was 33.5% ± 0.4%. After 1 min of the “Senobi” breathing, substantial up-regulation of sympathetic nerve activity and increased urinary hormone secretion were observed in the overweight women but not in the healthy controls. Moreover, after repeating the exercise for a month, the obese patients showed significant loss of body fat. The “Senobi” breathing exercise was found to be effective for weight loss in obesity possibly by regulating the autonomic nervous system and the hormone secretion.

著者

Keiichic Ohshima Sachiyo Takeda Mariko Hirose Yasuto Akiyama Kazuaki Iguchi Minoru Hoshino Ken Yamaguchi Tohru Mochizuki

出版者

バイオメディカルリサーチプレス

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.33, no.3, pp.191-199, 2012 (Released:2012-07-05)

参考文献数

29

被引用文献数

1 6

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Parathyroid hormone-related protein (PTHrP) contains a nuclear localization signal (NLS) sequence within 87-107. NLS sequences are generally capable of penetrating cellular membranes due to a richness of basic amino acid residues, and thus have been used as cell-penetrating peptides (CPPs) to translocate biologically active peptides/proteins into cells. The NLS sequence of PTHrP is not exception to this finding; however, PTHrP(87-107) contains 2 acidic glutamate residues at 99 and 101 within the basic amino acid stretch, which is not commonly observed in other CPPs such as HIV-1 Tat(48-60). In this study, we indicated structure-function relationship of the PTHrP NLS to understand the effect of acidic glutamate residues on cell permeability and intracellular localization. We chemically synthesized PTHrP(87-107) and its N-terminally truncated analogues. Their intracellular localization pattern was analyzed by microscopy, radioimmunoassay, and fluorescence-activated cell sorting. Although all analogues were translocated into cells, internalization by the cytoplasm and/or nucleus was length-dependent; specifically, PTHrP(97-107), PTHrP(95-107), and PTHrP(93-107) were more frequently localized in the cytoplasm. We assume that reduction in the net positive charge within PTHrP NLS analogues resulted in increased cytoplasm- translocation activity. We propose that PTHrP(97-107) is a useful carrier peptide for delivery and expression of cargo molecules in the cytoplasm.