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Aims Excessive vascular remodelling leads to progression of a wide range of vasculopathies, and the immune response to intimal injuries is crucial in this process. This vascular remodelling occurs in the hypoxic microenvironment and is closely related to the immune system. Macrophages play a key role in immunological-cell-mediated arterial remodelling. In this study, we clarified the role of macrophage-derived hypoxia-inducible factor (HIF-1α) in vascular remodelling. Methods and results Wire-induced femoral arterial injury was inflicted in mice lacking the macrophage-specific HIF-1α gene and in their wild-type counterparts. The mutant mice showed both suppressed wire-induced neointimal thickening and decreased infiltration of inflammatory cells in the adventitia, compared with wild-type mice. Studies to clarify the mechanism of restrained vascular remodelling in the mutant mice revealed decreased production of pro-inflammatory cytokines by the activated macrophages and suppressed macrophage migration activity in the mutant mice. Gene expressions of the HIF-1α-deficient macrophages positively correlated with the phenotypic profile of M2 macrophages and negatively correlated with that of M1 macrophages. Conclusion Our results show that HIF-1α in macrophages plays a crucial role in promoting vascular inflammation and remodelling. As decreasing HIF-1α activity in macrophages may prevent the progression of vascular remodelling, HIF-1α may be a possible therapeutic target in vascular diseases.

The policy of land use management for natural disaster mitigation has been shared globally as an increased number of natural disasters have occurred. Among them a set of unique systems have been established in England. The characteristics of the English systems are found in their quantitative risk assessment, flexible and process-oriented planning permission, and comprehensive land use control combined with regulations, insurance, risk information disclosure, and indirect intervention by the central government. On the other hand, another unique set of systems in this field have been established and in operation in France for more than 30 years. The characteristics of the French systems are found in its qualitative risk assessment, disaster-prevention-specific planning system independent of the standard city planning system, regulation by practical zoning harmonized with actual land use, and comprehensive land use control combined with different policy instruments and direct intervention by the central government. It is still evolving putting more emphasis on ex ante disaster prevention measures. Although neither the UK nor France has achieved perfect forms of land use management for flood disaster mitigation, every possible policy instrument is employed in their own unique way, and the best management system is being pursued by trial and error.

Such chiral phosphine–internal olefin hybrid type ligands as N-1-adamantyl-N-cinnamylaniline derivatives 1 with C(aryl)–N(amine) bond axial chirality were synthesized and utilized for the palladium-catalyzed asymmetric allylic alkylation of indoles to afford the desired products in high enantioselectivities (up to 98% ee).

Room temperature chiral spiro ionic liquids 1 and 2 based on 1,2,3-triazolium salts, were synthesized via an intramolecular double Huisgen reaction. The preparation of the enantiomerically pure spiro triazolium salts was achieved by resolution by HPLC using a chiral stationary phase column and subsequent N-dialkylations of spiro triazoles 6 and 10.

This study compares the performance of various spatial prediction models which consider spatial dependence among the real estate data in spatial econometrics, spatial statistics, and semiparametric statistics. Thus far, surprisingly few researches have been conducted from this perspective. This study employs the dataset of apartment rent in the Tokyo 23 wards for empirical comparison. This study in particular focuses on a geoadditive model which considers both spatial dependence and nonlinearity of a hedonic function, and suggests the predictive performance of this method superior to those of the traditional methods like kriging or EM type algorithm.

Laparoscopic liver resection (LLR) has become the standard treatment for various tumors of the liver including hepatocellular carcinoma (HCC) (1-3). LLR for liver tumors are considered to possess several perioperative advantages compared with conventional open liver resection (OLR). The Oslo-CoMet is the only randomized-controlled trial (RCT) to provide solid evidence that LLR is safer, less invasive, and cost-effective compared with OLR in patients with colorectal liver metastases (4).

The present protocol is applied to the synthesis of the naturally occurring aromatase inhibitor (VII).

A partition coefficient (λ) for Ra in gypsum was determined from coprecipitation experiment using oversaturation method. The λ-value derived for Ra was: λRa = 0.32±0.15. Saturation state was estimated with the initial concentration of Ca and SO42− in an experiment of the present study. Saturation index was calculated to be (0.49±0.02). This value was similar to those corresponds to analogous case where slow precipitation rate was kept in coprecipitation experiment for Sr in gypsum. Therefore, derived λ-value is thought to describe partition of Ra and Ca in solid phase and solution under an equilibrium condition without the effect of kinetic of precipitation. Determined λ-value was compared with those of other alkaline elements in sulfate minerals. The derived λ-value is smaller than that of Ra in barite and is similar to those of Sr in gypsum. This trend agrees with mechanical understanding for the size effect against partition coefficient.

To examine whether cerebrospinal fluid (CSF) histamine contents are altered in human narcolepsy and whether these alterations are specific to hypocretin deficiency, as defined by low CSF hypocretin-1.Patients meeting the ICSD-2 criteria for narcolepsy with and without cataplexy and who had CSF hypocretin-1 results available were selected from the Stanford Narcolepsy Database on the basis of CSF availability and adequate age and sex matching across 3 groups: narcolepsy with low CSF hypocretin-1 (n=34, 100% with cataplexy), narcolepsy without low CSF hypocretin-1 (n=24, 75% with cataplexy), and normal controls (n=23). Low CSF hypocretin-1 was defined as CSFor =110 pg/mL (1/3 of mean control values). Six of 34 patients with low CSF hypocretin-1, six of 24 subjects with normal CSF hypocretin-1, and all controls were unmedicated at the time of CSF collection. CSF histamine was measured in all samples using a fluorometric HPLC system.Mean CSF histamine levels were: 133.2 +/- 20.1 pg/mL in narcoleptic subjects with low CSF hypocretin-1, 233.3 +/- 46.5 pg/mL in patients with normal CSF hypocretin-1 (204.9 +/- 89.7 pg/mL if only patients without cataplexy are included), and 300.5 +/- 49.7 pg/mL in controls, reaching statistically significant differences between the 3 groups.CSF histamine levels are reduced in human narcolepsy. The reduction of CSF histamine levels was more evident in the cases with low CSF hypocretin-1, and levels were intermediate in other narcolepsy cases. As histamine is a wake-promoting amine known to decrease during sleep, decreased histamine could either passively reflect or partially mediate daytime sleepiness in these pathologies.

In this study, four Y-SNPs (M122, P31, M174 and M216) were analyzed in 207 Japanese males (Gunma, Fukui, Kagoshima and Tokushima Prefecture). Eleven Y-STRs, including DYS19, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS389, DYS385 and YCAII were also investigated in each prefecture. As a new technique, we used Cycleave PCR method with real-time PCR, which allows detection of Y-SNPs by an easier and faster method. Regarding Y-SNPs, each region in Japan could be almost classified based on two types, the D and O type. We found that the O type was remarkably higher in Kagoshima Prefecture than in other areas. Moreover, the D type was more prevalent than the O type in Gunma Prefecture, which is geographically located at the center of Japan. These findings of geographical differences may be related to the historical background and population movements of Japanese. Y-STRs were analyzed and data from Tokushima Prefecture that we previously reported was included in the analyses. As a result, DYS385 showed the highest gene diversity (GD) value (GD=0.953), while DYS391 showed the lowest GD value (GD=0.288). Haplotype diversity (HD) value of only Y-STRs (Extended haplotype) was estimated at 0.99981, whereas the HD value of Y-SNPs/Y-STRs was 0.9988.

Homogeneous partition coefficients (D) for Ra and Ba in calcite were determined from coprecipitation experiments using the Continuous Addition Method (CAM). The D-values derived for Ra and Ba are: DRa = (1.5 ±0.6) ×10-1 and DBa = (1.6 ±1.1) ×10-2. Although these data were derived at low precipitation rates (R) for calcite (R < 9 nmol mg-1min-1), the solutions were significantly oversaturated in calcite. Values of D should, ideally, be derived at equilibrium and hence the effect of oversaturation should be examined. Therefore, a coprecipitation experiment using the Free Drift Method (FDM) with slow degassing was also carried out. This experiment occurs under conditions that are only slightly oversaturated and the rate of coprecipitation was confirmed to be slow compared to dissolution and precipitation at the calcite surface. The resultant heterogeneous partition coefficients showed good agreement with homogeneous partition coefficients derived by CAM. This indicates that the oversaturation in CAM did not affect partitioning of these metals in calcite and that the derived D-values represented equilibrium partitioning between the solution and the solid phase. The derived value of DRa is one order of magnitude larger than that of DBa despite the larger ionic radius of Ra. This indicates that compatibility of ionic radius is not a dominant parameter for preferential incorporation of Ra and Ba in calcite.

A highly enantioselective aza-Morita–Baylis–Hillman (aza-MBH) reaction of isatin-derived ketimines with acrolein was established using β-isocupreidine (β-ICD) or α-isocupreine (α-ICPN) as a chiral acid–base organocatalyst. The present protocol readily furnished (S) or (R)-aza-MBH adducts with a chiral tetrasubstituted carbon stereogenic center in up to 98% ee.

We herein report two cases of thymomas diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). In both cases, the tumor was adjacent to the central airway. Therefore, we attempted to perform EBUS-TBNA in order to obtain specimens for a histopathological examination, which resulted in a diagnosis of thymoma. In one case, surgical resection was conducted and the histological evaluation of the resected specimen confirmed thymoma type AB, consistent with the histology from the EBUS-TBNA specimen. As a safe and minimally invasive procedure, EBUS-TBNA may be considered for the diagnosis of mediastinal tumors, including thymoma.

The enantioselective oxidative coupling of 2-naphthols in water was established using dinuclear vanadium(V/IV) catalysis with O2 as the sole co-oxidant. In the vanadium-catalyzed reaction, the corresponding coupling products were obtained in good to excellent yields with up to 94% enantiomeric excess. In water, racemization of the coupling product was suppressed even at high temperature (70 °C).

An enantio-, diastereo-, regio-, and chemoselective phosphine-catalyzed β,γ-umpolung domino reaction of allenic esters with dienones has been developed for the first time. The designed sequence, involving oxy-Michael and Rauhut–Currier reactions, produced highly functionalized tetrahydrobenzofuranones, bearing a chiral tetrasubstituted stereogenic center, in up to 96 % ee.

A highly enantioselective aza-Morita–Baylis–Hillman (aza-MBH) reaction of isatin-derived ketimines with acrolein was established using β-isocupreidine (β-ICD) or α-isocupreine (α-ICPN) as a chiral acid–base organocatalyst. The present protocol readily furnished (S) or (R)-aza-MBH adducts with a chiral tetrasubstituted carbon stereogenic center in up to 98% ee.

The present study examined the expression pattern of FOS in the hypothalamic peptide neurons during the sleep-dominant state induced by an adenosine A2A receptor agonist. The control rats, those that received the microdialysis-perfusion of their ventral striatum with artificial cerebrospinal fluid in the dark-active phase, spent 24% of the 90-min period prior to sacrifice in non-rapid eye movement (non-REM) sleep and 2.3% of that in REM sleep. These rats exhibited FOS, a transcription factor, in 21% of their orexin neurons and in 1.0% of their melanin-concentrating hormone (MCH) neurons in the perifornical/lateral hypothalamic areas. However, the rats perfused with 50 microM CGS21680, an adenosine A2A receptor agonist, spent 60% of the 90-min period prior to sacrifice in non-REM sleep and 11% of that in REM sleep. These rats exhibited FOS in 1.7% of their orexin neurons and FOS in 0.5% of their MCH neurons. When the sleep-dominant state was disturbed by mild stimulation and the rats were kept in the sleepy state by treatment with a sleep-inducing dose of CGS21680, the rats exhibited FOS in 13.3% of their orexin neurons, which percentage was about half of that for the control rats. These results suggest that the sleep-promoting process induced by this adenosine A2A receptor agonist was associated with a decline in the activity of orexin neurons. MCH neurons are not likely to change their activities during this sleep-promoting process.

症例は66歳,男性.上腹部不快感にて近医を受診.上部消化管内視鏡検査にて胃癌の診断であり,手術目的にて紹介受診された.上部消化管内視鏡検査にて胃癌は4型病変であり,生検にて印環細胞癌であった.腹部CT検査,超音波検査にて膵体尾部に腫瘤性病変を認めた. MRCPでは総胆管結石を認めるのみであったが, 3D-CT angiographyでは脾動静脈の途絶像を認めた.以上より胃膵重複癌の診断にて胃全摘+膵体尾脾合併切除術および総胆管切開術を施行した.病理学的検査にて膵病変は腺扁平上皮癌であった.胃癌の他臓器癌重複率は全悪性腫瘍のなかでも高いといわれているが,膵臓の重複率は低く,なかでも膵腺扁平上皮癌の合併は検索しうる限り本症例が初めてである.今回,われわれは極めて稀な症例を経験したので,若干の考察を加えて報告する.

症例は36歳,女性. 31歳時(平成11年3月)に上行結腸癌に対し,結腸右半切除術を施行され,術後補助療法として5-FU系内服薬を内服した.平成15年9月にFDG-PETにて骨盤内リンパ節の異常集積を指摘され,単発巣であったため切除術を施行した。病理学的検査所見は31歳時の大腸癌とは異なる所見であった.全身検索にて明らかな原発巣を認めず,原発不明癌リンパ節転移の診断であった.術後paclitaxel+carboplatinによる化学療法を施行した.同患者は平成16年11月にFDG-PETにて肝動脈周囲リンパ節転移を指摘された.またしても単発巣であり,また, CT上,左卵巣に嚢胞性病変を認めたため,肝動脈周囲リンパ節郭清術+単純子宮全摘術+両側附属器切除術を施行した.病理学的検索にてリンパ節は原発不明癌リンパ節転移,子宮および卵巣には悪性所見は認めなかった.平成17年ll月のPET検査では異常を指摘されておらず,原発不明癌としては良好な経過をたどっている.

This study investigated the relationship between participants' evaluation of creativiy and characteristics of creative products towards a clear and objective definition of the concept of creativity. Three experiments examined whether the size of "idea search space" in the creative process predicts the score of products in creativity assessments. In Experiment 1, in order to construct an multidimensional scaling (MDS) space which was supposed to correspond to creators' "idea space," 20 participants exhaustively evaluated the strength of semantic connection between every pair of 50 (physical) parts of possible creatures. In Experiment 2, 40 participants drew novel extraterrestrial creatures using five out of 50 parts used in Experiment 1. In Experiment 3, 20 participants assessed the creativity of each of the 40 drawings from Experiment 2. The results showed that a drawing with a larger idea search space estimated by the MDS score have a tendency to receive a higher creativity score. These results support the framework of idea search space and a possibility of explaining the creativity in terms of this model is suggested.

We applied Y-STRs (DYS385/DYS19/YCAII) to an adhesive plaster left at a crime scene. This plaster may have included body fluids from more than one person. Firstly, we performed preliminary examinations, ABO-blood type examinations, and commonly used DNA examinations (D1S80, HLADQα, TH01, and PM) on these specimens. As a result of these examinations, we could evidence that suspect A did not contacted with the plaster, but could not confirm the presence of perspiration from suspect B. As the next step, we applied Y-STR examination to the plaster. Using this examination, we detected alleles that coincided to those of suspect B. We also concluded that the fluid from an unidentified person was vaginal fluid based on crime scene investigation. Y-STRs examination data obtained from 124 persons in Tokushima prefecture showed that 1.613% of individuals demonstrated haplotypes 10-18/ 15/19-23, which was detected from the plaster and from suspect B. Therefore, we considered that there was a high probability that the persiration detected in the plaster was that of suspect B. Based on these studies, we concluded that Y-STR examination of trace evidence was very useful to screen suspects using materials that contained body fluid from more than one person. J. Med. Invest. 51 : 238-242, August, 2004

A putrefied cadaver of q middle-aged woman was found drifting in the “Kii” water course. Autopsy findings indicated that the postmortem duration was about one week, and the cause of death was assumed to be drowning. In this case, a nail was collected as a sample for personal identification. After five months of police investigation, persons thought to be her family, husband and child, were found. A combination of D1S80 and the short tandem repeat (STR) typing system using an AmpFlSTR ProfilerTM PCR Amplification kit was performed for identification. Nine STRs (D3S1358, vWA, FGA, TH01, TPOX, CSF1PO, D5S818, D13S317 and D7S820) and Amelogenin were analyzed by this kit. Those DNA typings successfully confirmed the family relation for personal identification of the cadaver. This analysis system may be useful for identification of a decomposed cadaver.

Using two different canine models of narcolepsy, we evaluated the therapeutic effects of hypocretin-1 on cataplexy and sleep.Intracerebroventricular administration of hypocretin-1 (10 and 30 nmol per dog) but not intravenous administration (up to 6 microg/kg) induced significant wakefulness in control dogs. However, hypocretin-1 had no effect on cataplexy or wakefulness in hypocretin receptor-2 gene (Hcrtr2) mutated narcoleptic Dobermans. Only very high intravenously doses of hypocretin-1 (96-384 microg/kg) penetrated the brain, to produce a short-lasting anticataplectic effect in a hypocretin-ligand-deficient animal.Hypocretin-1 administration, by central and systemic routes, does not improve narcoleptic symptoms in Hcrtr2 mutated Dobermans. Systemic hypocretin-1 hardly crosses the blood-brain barrier to produce therapeutic effects. The development of more centrally penetrable and longer lasting hypocretin analogs will be needed to further explore this therapeutic pathway in humans.

A two-year-old male chihuahua suffered attacks of muscle weakness and immobility, although it had no family history of paroxysmal attacks. No neurological or blood biochemical abnormalities were recorded when it was first examined. The attacks were typically elicited by stimulation, such as feeding, and a case of sporadic narcolepsy-cataplexy was therefore suspected. Treatment orally three times a day with 1 mg/kg imipramine, was effective in reducing the attacks. The concentration of hypocretin-1/orexin A in the dog's cerebrospinal fluid was less than 80 pg/ml (22.5 pmol/litre), compared with normal canine levels of 250 to 350 pg/ml (70.0 to 98.3 pmol/litre), supporting a diagnosis of hypocretin-deficient narcolepsy.

By using forward and reverse genetics, genes involved in the pathogenesis of narcolepsy (hypocretin/orexin ligand and its receptor) in animals have been identified. Mutations in hypocretin-related genes are extremely rare in humans, but hypocretin ligand deficiency is found in many cases. A series of these discoveries are representing the most striking progress in narcolepsy research in the last 100 years, and should continue to contribute to the development of new diagnostic tests and treatments. Impacts of the hypocretin system on sleep physiology have also rapidly increased. Hypocretins/orexins are novel hypothalamic neuropetides discovered outside the sleep research field by using subtractive polymerase chain reaction/reverse pharmacology techniques. Hypocretins are involved in various fundamental hypothalamic functions such as feeding, energy homeostasis and neuroendocrine regulation. Hypocretin neurons project to most ascending arousal systems (including monoaminergic and cholinergic systems), and generally exhibit excitatory inputs. Together with the recent finding of the sleep promoting system in the hypothalamus, especially in the γ-amynobutyric acid (GABA)/Galanin ventrolateral preoptic area, which exhibits inhibitory inputs to these ascending systems, the hypothalamus is now recognized as the most important brain site for the sleep switch. Meanwhile, narcolepsy now appears to be a more complex condition than previously thought. The pathophysiology of the disease is involved in the abnormalities of sleep and various hypothalamic functions caused by the hypocretin deficiency, such as the changes in energy homeostasis. Narcolepsy is thus an important model to study the fundamental hypothalamic function and the links between sleep regulation, energy homeostasis and/or feeding.

Correction for ‘Hydrazone-Pd-catalyzed direct intermolecular reaction of o-alkynylphenols with allylic acetates’ by Kohei Watanabe et al., Org. Biomol. Chem., 2018, 16, 575–584.

Correction for ‘Hydrazone–palladium catalyzed annulation of 1-cinnamyloxy-2-ethynylbenzene derivatives’ by Kohei Watanabe et al., Org. Chem. Front., 2016, 3, 979–984.

Unique chiral spiro ionic liquids based on 1,2,3-triazolium salts were synthesized via an intramolecular double Huisgen reaction. The optical resolution of the liquid precursors and subsequent dialkylations leads to chiral spiro triazolium salts on a gram scale.

Enantioselective organocatalytic synthesis of tetrahydropyridines bearing a chiral tetrasubstituted carbon stereogenic center has been achieved. The spiro-type monoaryl phosphine catalyst, (R)-SITCP, was found to promote the formal [4+2] cycloaddition of saccharin-derived ketimines and α-methyl allenoate to afford the corresponding six-membered N-heterocycles in high yields and excellent regioselectivities with up to 93% ee.

Axially chiral vanadium complexes catalyze the enantioselective oxidative-coupling of polycyclic phenols to biphenols.

The introduction of a 1,3-propanediamine unit at the 3-position of ( S )-BINOL using a methylene spacer led to the formation of a chiral bifunctional organocatalyst for the aza-Morita–Baylis–Hillman (aza-MBH) reaction. The organocatalyst 1k mediated aza-MBH transformations with high chemical yields and with up to 82% ee.

Hypocretins/orexins are neuropeptides implicated in sleep regulation and the sleep disorder narcolepsy. In order to examine how hypocretin activity fluctuates across 24 h with respect to the sleep-wake cycle, we measured changes in extracellular hypocretin-1 levels in the lateral hypothalamus and medial thalamus of freely moving rats with simultaneous sleep recordings. Hypocretin levels exhibited a robust diurnal fluctuation; levels slowly increased during the dark period (active phase), and decreased during the light period (rest phase). Levels were not correlated with the amount of wake or sleep in each period. Although an acute 4-h light-shift did not alter hypocretin levels, 6-h sleep deprivation significantly increased hypocretin release during the forced-wake period. Hypocretin activity is, thus, likely to build up during wakefulness and decline with the occurrence of sleep. These findings, together with the fact that a difficulty in maintaining wakefulness during the daytime is one of the primary symptoms of hypocretin-deficient narcolepsy, suggest that hypocretin activity may be critical in opposing sleep propensity during periods of prolonged wakefulness.

A 78-year-old man was admitted to Kumamoto Rosai Hospital with right lower abdominal pain. Abdominal computed tomography (CT) showed penetration of the cecum by a foreign body, which looked like a fish bone, as well as thickening of the right lower abdominal wall. We made an initial diagnosis of penetration of the colon by an ingested fish bone and the patient was managed conservatively with fasting, peripheral parental nutrition, and intravenous antibiotics. By the next day, the right lower abdominal pain had diminished and a repeat CT scan showed that the fish bone had moved to the splenic flexure. However, 2 days later, the patient complained of pain in the left upper abdomen and another CT scan showed repeated penetration of the descending colon by the same fish bone. Thus, we removed the fish bone via endoscopic extirpation. The patient had an uneventful postoperative course and was discharged home 6 days later.

Thirty-six beagles, 18 months of age, underwent ovariohysterectomy (OHX) or a sham operation. Sham-operated animals were given a diet with standard calcium (1.4%) (group 1, n = 6) or a restricted calcium diet (0.14%) (group 2, n = 6). The OHX animals were given the restricted calcium diet and YH529 orally with respective daily doses of 0, 0.02, 0.1, and 0.5 mg/kg of body weight (groups 3-6, n = 6 each) for 12 months. At the end of this period, the lumbar bone mineral densities (BMDs) in groups 2 and 3 and the load values for group 3 were significantly smaller than those for group 1. The midfemur BMD did not differ among the groups. The urinary deoxypyridinoline (U-Dpy) and bone formation rates (BFR/BS, BFR/BV) in groups 2 and 3 and the osteonal BFR/BS and trabecular osteoclast number (Oc.N/BS) in group 3 were significantly larger than the respective values for group 1. However, these parameters did not significantly differ between groups 2 and 3. The serum osteocalcin (OC) level, wall thickness (W.Th), and mineral apposition rate values for group 3 were significantly larger than those for group 2. In group 2, the trabecular activation frequency (Ac.F) increased by 3.11 times, and the percent values of the number of labeled osteons (L-Ot.N/T-Ot.N, %) in the tibia by 3.28 times over those for group 1. In group 3, the Ac.F increased by 3.20 times and the number of labeled osteons by 3.77 times over those for group 1. In groups 4-6, the U-Dpy and Oc.N/BS values were smaller, but their OC levels did not significantly differ from the level for group 3. The lumbar BMD, the load, and W.Th were dose-dependently significantly larger than those for group 3. The Ac.F values were significantly smaller, and the respective value in groups 4-6 was 67.9, 25.5, and 10.2% of that in group 3. The BMDs of the midfemur in groups 4-6 were significantly larger than those in group 3, but the ultimate load values did not significantly differ. The L-Ot.N/T-Ot.N values were also significantly smaller, and the respective value in groups 4-6 was 82.0, 48.5, and 55.2% of that in group 3. The tibial endocortical and periosteal BFR/BSs did not differ significantly. These data demonstrate that the effects of OHX on bone mass and turnover were small in the beagles fed a restricted calcium diet. YH529 maintained the mass and strength of the lumbar bone by reducing the bone resorption. The cortical bone appeared to be less sensitive to the agent than the trabecular bone in this animal model.

The patient was an 82-year-old man who had undergone resection of a gastrointestinal stromal tumor(GIST)of the small intestine in January 2000, when he was 69 years old. As peritoneal recurrences were diagnosed in June 2002, we performed peritoneal tumorectomy twice, and the perirectal tumor was controlled with imatinib for over 7 years. Resistance to imatinib was diagnosed in March 2011, and treatment was switched to sunitinib. Administration of sunitinib was started at 50mg/day for 28 days followed by treatment withdrawal for 14 days; however, the dose needed to be reduced twice and then discontinued owing to the occurrence of side effects and pemphigoid. During discontinuation of sunitinib, the tumor increased in size and cancer pain appeared; therefore, sunitinib was re-administered at a very low-dose of 12.5mg every alternate day. Low dose sunitinib was effective; the perirectal tumor was reduced and cancer pain disappeared.