The crystal structure of 3, 7, 11, 15-tetramethyl-2, 4, 6, 10, - trans-hexadecapentaenoic acid (E-5166) was determined by the X-ray method. The compound crystallized in a space group P1, with unit cell dimensions a=11.674 (3), b=11.375 (3), c=7.367 (2) Å, α=106.57 (2)°, β=81.75 (2)°, γ=93.95 (2)°. The final R-value was 0.062 for 2270 reflections.

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Various derivatives of aphidicolin (1) were prepared and their inhibitory effects on purified DNA polymerase α in vitro were assayed. Among these derivatives, the new 3α-, 17, 18-trihydroxyaphidicol-15-ene (24) was as inhibitory as the known 3-deoxy-and 3-oxoaphidicolins, (20) and (). the other derivatives with modification of any of the hydroxyl groups of 1 had no effect on the enzyme in vitro. The structure-activity relationships are discussed concerning functionalization on the aphidicolane ring.

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The neurological manifestations of twenty-one Japanese patients with Sjögren's syndrome (SjS) were evaluated. All patients were women, and sixteen of the twenty-one cases (76%) demonstrated objective abnormal neurological symptoms, the most frequently observed of which was trigeminal neuropathy (50%). Multiple mononeuropathy was seen in almost one-third of the examined cases (31%). Central nervous system (CNS) involvement was observed in three cases (%). of these values differed greatly from those previously reported. Therefore, this study revealed characteristic features of Japanese SjS and also implied the existence of different immunopathological mechanisms associated with SjS in Japanese patients.
(Internal Medicine 36: 690-693, 1997)

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Dust accummulation in paddy drying, processing, and storage facilities was examined, and explosibilities of the dust collected in these facilities were tested by means of the Hartmann apparatus.
The dust deposited was 100-500 (g/m²) in the examined facilities and dust cloud was expected to be easily formed. The predominant substance in the dust was rice hairs (pubescences).
Chemical and phisical properties of the dust were as follows: moisture content 9-12% d. b., volatile matter content 38-50, ash 35-54, fixed carbon 8-14% moisture free basis, median particle diameter 20-60μm, calolific value 1930-2450cal/g.
In the explosibility tests, even with the undried dusts (moisture content 9-%), the dusts tested exploded. It can be thought that the danger of explosion is reat. The dried dusts through 200 mesh sieve indicated maximum explosion pressure of 4.3-6.1 (kg/cm²) and maximum pressure rise of 73-141 (kg/cm²·sec).

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The investigation using digital filtering on the auditory middle latency response (MLR) to click was performed and the results were compared in infants and adults.
The subjects were 10 children aged 8 to 10, and 7 children aged 11 to . of them were proved to have normal hearing. The waveforms of the infants changed gradually into the waveforms of the adults during the age of 8 to 14. Pa detectability on high pass filtering of 40Hz and Pb detectability of 20-40Hz increased gradually with aging, and reached to the adults score (100%). The peak Pa and Nb decreased in latency with aging. From these results, the existence of the maturational effects on the MLR is recognized, and the infant MLR changes into the adult MLR in around 13 to 14 years old.

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A panel screening using cdc mutants of Schizosaccharomyces pombe identified radicicol as a potent growth inhibitor of certain mutants at the permissive temperature. The strains sensitive to radicicol were cdc7, cdc11, and cdc, of which are defective in early septum formation. Cytokinesis but not nuclear division of these mutants was inhibited by radicicol, but that of cells with the wild-type background was not. A biologically active derivative of radicicol with a biotin moiety at the C-11 position bound Swo1, an Hsp90 homologue in S. pombe. Increased Swo1 expresion partially suppressed radicicol sensitivity of cdc14 and almost completely rescued morphological abnormalities in cdc14 and cdc7 cells induced by radicicol at the permissive temperature. On the other hand, the increased Swo1 expression did not restore septum formation at the nonpermissive temperature. These results suggest that Swo1, as a molecular chaperone, plays a role in stabilizing these temperature-sensitive proteins at the permissive temperature or in activating the cytokinesis signaling cascade.

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Liver X receptors (LXRs) are members of the nuclear receptor superfamily. LXRs include two subtypes, LXRα and LXRβ, which have different tissue distributions. LXRα is highly expressed in liver, intestine, adipose tissue, and macrophages, on the other hand, LXRβ is ubiquitously existed in organs and tissues. They are ligand-activated transcription factors involved in the regulation of cholesterol and lipid metabolism. Many synthetic LXR agonists have been reported including T0901317 and GW3965, however, most of them do not show subtype selectivity. Therefore, we planned to synthesize novel LXR agonists possessed potent agonistic activity as well as subtype selectivity. The synthetic scheme of our desired compounds was started from naphthoquinone derivatives such as menadione and 2,3-dichloro-1,4-naphthoquinone. Introduction of substituents including aniline, piperidine, pyrrolidine, and morpholine to naphthoquinones in one or two steps lead to desired compounds 1-. the synthetic ligands were tested in assays that measured the LXR-mediated transcriptional activity. We investigated transcriptional activity of those compounds through LXRα and LXRβ. Compound 6 and 8 showed weak LXRβ-agonistic activity, whereas compound 8 and 14 exhibited potent LXRα-agonistic activity among the compounds. We also evaluated docking studies to better understand the binding modes of compounds to LXR at the atomic level.

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Esophageal epithelial lesions are important features with respect to the early diagnosis of esophageal cancer. Such lesions include inflammatory reactive lesions (inflammatory reactions, IR) and neoplastic lesions. However, while neoplastic lesions are also classified from low-grade intraepithelial neoplasia (LN) to high-grade intraepithelial neoplasia (HN), it is often difficult to differentiate esophageal epithelial lesions in a biopsy. Therefore, this study analyzed cases of endoscopic mucosal resection (EMR) and dissection by immunostaining for p53, MIB-1, glucose transporter-1 (GLUT-1), and cytokeratin (CK) in addition to cytohistological grading to establish lesions trends for classification. This study included 50 lesions of EMR performed at our hospital from 2004 to 2007, as well as 31 cases who underwent a pathological autopsy at our hospital during the period between 2006 and 2007. Tissue diagnoses by HE staining classified the specimens into five groups: normal, IR, LN, HN, and squamous cell cancer (SCC). This study undertook further comparison by immunostaining for p53, Ki-67 staining, GLUT-1 and CKs 17 and . immunostaining revealed a significant difference between IR and LN grade of lesions. Specifically, GLUT-1 staining revealed a significant difference between LN and HN lesions, while CK17 staining differentiated significantly between HN and SCC. The findings indicated that pathological diagnoses of esophageal lesions should include GLUT-1, CK17, and CK14 immunostaining to differentiate LN and HN lesions.

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To investigate the anti-ulcer activity of the isoprenyl chalcone, sophoradin, which is present in a Chinese crude drug, Guang-dou-gen (the root of Sophora subprostrata), 30 related chalcones (1-30) were newly synthesized by condensation between substituted acetophenones and benzaldehydes, and their anti-ulcer activities were examined using Shay's pylorus-ligated rats, and water-immersed and restraint stress rats. Twenty-seven chalcones were substituted with isoprenyl or isoprenyloxyl groups and two with geranyloxyl groups (13, 30), with or without a carboxymethoxyl group, and one chalcone was substituted with allyloxyl group (). the chalcones were found to be effective by both methods. Several chalcones (2, 3, 8, 10, 11, 12, 15, 17, 22), each having more than one isoprenyloxyl group, exhibited high inhibitory ratios by both methods. In particular, 2', 4'-dihydroxy-3'-(3-methyl-2-butenyl)-4-(3-methyl-2-butenyloxy) chalcone (2), 2'-hydroxy-4, 4'-bis (3-methyl-2-butenyloxy) chalcone (10), and 2'-carboxymethoxy-4, 4'-bis (3-methyl-2-butenyloxy) chalcone (15) exhibited very high inhibitory ratios (70-100%) by both methods, and were as potent as sophoradin.

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The anthelmintic efficacy of oral paste formulations of ivermectin against gastrointestinal parasites in horses was evaluated, using fifteen active racehorses in which nematodes had been detected in their gastrointestinal tracts by fecal examination. A single dose of ivermectin was given orally to twelve horses of the treatment groups at a dosage rate of 200 μg/kg in order to obtain and identify gastrointestinal parasites in their feces for 3 days after treatment. Small strongyles, strongyles, and Parascaris equorum were found passed in feces up to post-treatment day (PTD) 2, but they were no longer observed on PTD 3. Horse bot fly Gasterophilus spp. larvae were found on PTD 2 and 3. The percentages of small strongyles found on PTD 1 were 75-100% (88% on average), and the rest were found (12% on average) on PTD 2. The nematodes were 16 species from 7 genera, of which 11 species were identified as small strongyles. In the fecal examination conducted on PTD , horses of the treatment groups showed negative for nematode eggs. No abnormalities were observed in general clinical signs of the treated horses for 14 days after treatment. Three non-treated horses of the control groups still showed positive for nematode eggs on PTD 14. These results confirm that when ivermectin was given orally to horses at a dosage rate of 200 μg/kg, small strongyles, strongyles, and P. equorum, were excreted in feces up to PTD 2, and Gasterophilus spp. larvae on and after PTD 2, demonstrating the potent anthelmintic efficacy of ivermectin against these parasites.

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Three new minor diterpene alkaloids, ezochasmanine 12, ezochasmaconitine 9 and anisoezochasmaconitine 10 together with major alkaloids pseudkobusine 2 and chasmanine 8 were isolated from Aconitum yesoense Nakai. (Chart 1). The structures of new bases 12, 9 and 10 have been established as 3-α-hydroxychasmanine, 14-acetyl-8-benzoylchasmanine and 14-acetyl-8-anisoylchasmanine respectively. The structure of ezochasmanine 12 was first postulated from it's ^<13>CNMR spectrum and ^1HNMR spectrum of the 3-acetyl derivative. To confirm the structure, transformation of ezochasmanine 12 to chasmanine 8 of known structure was carried out as shown in chart 3. Ezochasmaconitine 9 and anisoezochasmaconitine 10 were synthesized from chasmanine 8 by two steps via. acetylation, benzoylation or p-anisoylation. These two alkaloids are the first examples of the diterpene alkaloids possessing the aroyl groups at C8 and acetyl group at C. of the formerly known congeners have the aroyl groups at C14 and acetyl group at C8. Mild toxicity was observed for the two new bases, 9 and 10. Isodelphonine 33 which is an alkamine of isodelphinine 34, was stereoselectively synthesized from chasmanine 8 as described below. (Chart 4). Oxidation of diacetylchasmanine 27 with KMnO_4 in aqacetone gave the des-N-ethyl derivative 28, which was then formylated to give N-formyl compound 29. Pyrolysis of 29 gave the Δ^<8,15> olefinic derivative 30, which was converted into epoxy derivative 31 by m-CPBA oxidation. Ring opening reaction of 31 using formic acid gave rise to the trans diol derivative 32 which was reduced by LiAlH_4 to yield isodelphonine, mp 135-137°, 33.

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The investigation of the transfer of radio-activity from prelabelled cell debris to particulate fractions in the cell-free prepara-tions of the posterior silkgland was developped.
1. After labelling of silkglands with C¹⁴-glycine for 15 minutes in vivo or in vitro, posterior silkglands were collected and homogenized. The cell debris fraction was obtained by centrifugation at 700×g for 10 minutes. Microscopic observation of cell debris revealed that major components were nuclear debris and fragments of cell membranes without any intact cells.
2. Prelabelled cell debris thus prepared was highly radioactive and it was shown that under appropriate conditions, the radioactivity was transferred enzymatically to particulate protein. This was confirmed by dinitrophenylation study of isolated particles after the reaction.
3. Radioactivity was principally incorporated into protein of particulate fractions, but not very much into lipid and supernatant fractions.
4. As regards the transfer reaction, amino acid activating enzyme (E₃) seemed to be unnecessary, whereas amino acids mixture, GTP, ATP and ATP-generating systems were required.
The work has been supported by grants partly from the Ministry of Education to the research group for Fibroin Biosynthesis and partly from the Rockefeller Foundation to one of the authors. We wish to thank Dr. K. Shimur a and his staff for their valuable discussion and Dr. B. Maruo for his kind supply of --labelled amino acids.

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Background:Guide catheter-induced iatrogenic coronary artery dissection is a rare but feared complication. When it occurs, bailout stenting is widely performed; however, its prognosis and the impact of stent type remains unclear.

Methods and Results:The study population consisted of 77,257 consecutive patients (coronary angiography, 55,864; percutaneous coronary intervention, 21,393) between 2000 and 2015. We investigated the incidence, clinical outcomes, and angiographic results after bailout stenting and compared by stent type: bare-metal stent (BMS) and drug-eluting stent (DES). Iatrogenic coronary artery dissection occurred in 105 patients (incidence rate, 0.

%). cases of iatrogenic coronary artery dissection that were recognized as requiring bailout procedure could be managed by stent implantation, and no patients died during bailout procedure. The 5-year cumulative incidences of cardiac death, target lesion revascularization, and major adverse cardiac events were 11.3%, 10.3%, and 21.0%, respectively. The binary restenosis rate was 10.4%, and it was not significantly different between BMS and DES implantation. In lesions with preprocedural stenosis, however, it was significantly lower in the DES group than in the BMS group. On the other hand, coronary artery dissection recurred in 8 patients, which was observed only after DES implantation.

Conclusions:The immediate and long-term outcomes of bailout stenting for iatrogenic coronary artery dissection were acceptable. Although DES may be favorable for stenotic lesions, coronary artery dissection can recur after DES implantation.

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Venous thromboembolism (VTE) is a life-threatening complication after trauma. Several studies have reported VTE prophylaxis using low-molecular-weight heparin; however, there is no consensus for prophylaxis after trauma. This study aimed to assess the efficacy and safety of our new anticoagulation therapy protocol using unfractionated heparin (UFH) plus intermittent pneumatic compression (IPC) to prevent post-traumatic VTE in high-risk trauma patients.

This study enrolled 70 trauma patients who were admitted to the emergency medical center of Nagasaki University Hospital and had Risk Assessment Profile (RAP) scores ≥ 5. After stopping bleeding at the trauma site, all patients received intravenous UFH (10,000 U/day) plus IPC, which was continued for 14 days or until the patients could walk. On days 7 and

, patients underwent lower extremity sonography for deep-vein thrombosis screening. VTE incidences between patients with the above intervention and historical controls with IPC alone were compared.

No significant differences in age, sex, and the RAP score were observed between the 105 controls and intervention patients. VTE occurrence was fewer in patients with the intervention (14.3%) than in the controls (28.6%; P = 0.029). No hemorrhagic complications occurred after UFH administration. Multivariable logistic analysis revealed a significant association between the intervention and low incidence of VTE (odds ratio: 0.390; 95% confidence interval: 0.163-0.913; P = 0.030).

Routine UFH administration with IPC may prevent post-traumatic VTE without adverse events.

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Background: As an endocrine disruptor, bisphenol A (BPA) exposure has been implicated as a potential risk factor in childhood obesity, which is defined using percentiles of body mass index for age. We aimed to examine the associations between BPA exposure, reflected by urinary BPA concentration, and body composition in American children.

Methods: Data of 1860 children aged 8–19 years who participated in the 2003–2006 National Health and Nutrition Examination Survey (NHANES) were analyzed in this study. Urinary BPA concentration (ng/mL) was used to indicate BPA status in the body. Body composition was measured by dual-energy X-ray absorptiometry (DXA). Multivariate linear regression models were fitted using survey procedures to investigate the associations between urinary BPA level and body composition separately for boys and girls.

Results: After adjusting for demographic and lifestyle covariates, higher quartiled and log-transformed urinary BPA levels were significantly associated with elevated lean body mass index (LBMI) z-scores in boys (p < 0.05), and significantly associated with elevated fat mass index (FMI) z-scores in girls (p < 0.05). Lower urinary BPA concentration was associated with lower percentage of trunk fat in girls (compared to 1st quartile, 2nd-quartile: β = 2.85, 95% CI, 0.92–4.78; 3rd-quartile: β = 2.57, 95% CI, 0.28–4.85; 4th-quartile: β = 2.79, 95% CI, 0.44–5.

; p < 0.05). Such patterns were not observed in boys.

Conclusions: Higher BPA levels may be associated with elevated LBM in boys, but not in girls, while higher BPA levels may be associated with elevated FM in girls, but not in boys.

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We aimed to compare the combinatorial effect of 3,4,5-trihydroxybenzoic acid (THB) and oregano extracts (OE) with THB alone on the growth performance and elimination of deleterious effects in coccidiosis-infected broilers. A total of 210 one-day-old broilers were randomly assigned to one of five dietary treatments, with six replicates each, for 35 days. Dietary treatments were: 1) non-challenged, non-treated (NC); 2) challenged, non-treated (PC); 3) PC+Salinomycin (0.05 g/kg; AB); 4) PC+THB (0.1 g/kg; THB); and 5) PC+THB+OE (0.1 g/kg; COM). On day

, groups except for NC were challenged with a 10-fold dose of Livacox^® T anticoccidial vaccine to induce mild coccidiosis. All treatments significantly improved (P<0.05) body weight, average daily gain, and average daily feed intake, compared to PC, on days 21, 28, and 35. However, all treatments significantly reduced (P<0.05) the feed conversion ratio of PC by more than 14.60% on day 35, 11.76% during growing period, and 10.36% through the entire period. Broilers receiving anticoccidial treatments had 54.23% and 51.86% lower lesion scores (P<0.05) at 4 and 7 days post-infection, respectively, compared to PC. Additionally, the villus height of COM was significantly longer (P<0.05) than that of THB. Although the molecular action of COM remains unclear, OE addition to THB reduced the shedding of oocysts better than THB alone (P<0.05, 9-11 days post-infection). Most importantly, COM effectively minimized the mortality of challenged birds from as high as 11.90% (PC) to 0%, a level similar to NC and AB, while THB maintained a mortality of 2.38%. In conclusion, the anticoccidial effect of THB can be enhanced by the addition of OE for better animal performance and the elimination of deleterious effects from coccidiosis-infected broilers for 35 days.

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Background This study tested the hypothesis that shock wave (SW) therapy applied to bone marrow-derived mononuclear cells (BMDMNCs) enhances the formation of vascular endothelial growth factor (VEGF) and positively stained CD31 (CD31+) cells, an endothelial phenotype. Methods and Results The BMDMNCs (~1.2×10⁶ cells/2 femoral bones) were obtained from adult male Sprague-Dawley rats and SW therapy was applied once to BMDMNCs in group I (140 SW: defined as 140 shots in total, given at 0.09 mJ/mm²), group II (280 SW), and group III (560 SW). Group IV was not treated by SW and served as the control group. Six experiments were done in each group. The BMDMNCs were cultured following SW therapy and the supernatants were collected on days 1, 3, 7 and 14 for assessment of VEGF levels. Immunocytochemical staining and flow cytometric measurement were performed on days 0 and 14. Experimental results demonstrated that VEGF levels were significantly higher in groups I-III than in group IV, and in group II than in group I at all intervals, and in group II than in group III on day ( p values <0.005). Additionally, the number of positively stained VEGF cells on days 1, 3 and 14 and the number of newly formed CD31+ cells on day 14 were significantly higher in group II than in group IV (all p values <0.001). Conclusions These data suggest that application of SW to BMDMNCs significantly enhanced VEGF production and promoted differentiation of BMDMNCs into endothelial phenotype cells. (Circ J 2008; 72: 150 - 156)

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本研究ではアレルギー性皮膚炎の猫43例（アトピー性皮膚炎14例，食物アレルギー15例，ノミアレルギー14例）から採材した皮膚生検標本における，血管周囲性～間質性の好酸球性炎症の組織学的な深度について検討した。本研究で解析された全ての猫において，“粟粒性皮膚炎”または“発疹を伴わないかゆみ”のいずれかの反応パターンが認められた。93％の猫では，細胞浸潤が真皮浅層と深層の両方に認められた。組織学的な反応パターンと，臨床診断あるいは臨床的な反応パターンとの間に相違は認められなかった。

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