Effect of an antirheumatic gold compound, Auranofin (

), have been revealed.  1-10 µM of inhibited prostaglandin (PGE₂) production and nitric oxide (NO) production in macrophages treated with some stimulatory compounds.  We found that reduced cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) mRNA levels, but not affected their enzyme activities.  We then revealed that partly inhibited the nuclear-translocation of NF-κB while PGE₂ production was almost completely inhibited.

  In the review on manuscripts,

is reported to down-regulate the mRNA levels of SLC47A1, , ATP1A3, ABCG2, SLCO1B1, PIK3CA, and up-regulate the mRNA levels of ABCC3, ABCB1, , ABCC2, SLC31A2, CLTD, CLTB.  PGs are known to be transported by transporters, OATP-PG (SLCA), SLC21A2 (OATP2A1, SLCO2), SLC21A11 (OATP3A1), and ABCC, though I could not identify whether reduced PGE₂ concentration in cellular cultured medium as described above via these transporters by downregulation for export of PGE₂.

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1, an ets-oncogene family transcription factor, has been shown to upregulate transcription from matrix metalloproteinase (MMP) genes, which confers the invasive phenotype on cancer cells. On the other hand, we have demonstrated by luciferase assay that 1 positively regulates transcription from the p21^waf1/cip1 promoter. Ca9. cells were transfected with a metallothionein-inducible 1 expression vector (Ca9.MTF) to investigate the relationship between invasive ability and cell cycle modulation caused by 1. MMP-9 and p21^waf1/cip1 protein were synergistically increased in the ZnCl₂ stimulated CA9.MTF cells, and both proteins were identified in the same cells when 1 was induced. These results imply that invasive growth of tumor cells occurs in the static state of the cell cycle and that 1 plays a key role in this phenomenon.

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In the first part of the present work the interaction of glycophorin with dimyristoylphosphatidylcholine (DMPC) is studied by freeze fracture electron microscopy, densitometry, calorimetry, and 90° static light scattering. An exothermic lipid/protein interaction energy of W_P=190 kJ•mol^-1 was found by application of the well known Van Laar relation for the displacement of the freezing point and the Gibbs-Duhem relationship. Secondly, the effects of Ca²⁺ on the lipid/protein interaction were studied. Following Ca²⁺ addition a remarkable decoupling of the interaction of the glycophorin head group with the bilayer surface was revealed by densitometry and gold-labeling electron microscopy. It is estimated that about 80% of lipid once disturbed by the adsorption of glycophorin head groups is decoupled after addition of Ca²⁺. Thirdly, the selective interaction of glycophorin with binary lipid mixtures was studied, including the mixtures of DMPC with dimyristoylphosphatidylserine (DMPS) and dilauroylphosphatidylcholine (DLPC), and the mixture of dipalmitoylphosphatidylcholine (DPPC) with DLPC.

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Our studies on the constituents of so far above forty species of Solanum genera plants have resulted in the isolation of steroidal glycosides potent cytotoxity, antifeedant, anti HSV-1 activities and of the key intermediate on the biosynthesis of solasodine. On the way of these Solanum plants investigation, unusual peculiar steroidal saponins with opened -ring type, -1024, which corresponds to the precursor of the spirostanol and furostanol, 16,-dicarbonyl type steroids, -a-1 and -2, and a 20--seco-type steroid, SNI-14, have been obtained together with many usual furostanol and spirostanol type glycosides from some Solanum genera, three formers of which were from the fruits of Solanum anguivi, and the latter from the aerial parts of Solanum nigrum, respectively. The structure of -1024 was characterized as 3-O-chacotriosyl 3,16,,26-tetrahydroxycholest--ene 26-O- -D-glucopyranoside. The configurations at C-16 and - were not defined, however, this compound is regarded as an important precursor which would produce furostanol and spirostanol showing a variety of bio-activities. -a-1 and -2 were assumed to be isomers at C-23. The structure of -a-1 was characterized as 3-O- -chacotriosyl (23S,26)-23,26-epoxy-3,26-dihydroxycholest--ene-16,-dione. On alkaline treatment, both afforded the identical product. This compound was shown to be 3-O- -chacotriosyl 20-caboxypregna--ene 16-one. The occurrence of -a-1 and -2 are regarded as genuine constituents probably produced directly from -1024 on the biogenetic route. The structure of SNI-14 was characterized as 3-O- -lycotetraosyl 3,16,20(S)-trihydroxy- -pregnane 16-O-(-O- -D-glucopyranosyl-(S)-methyl--hydroxypentanoic acid)-ester. This compound was supposed that it would be produced via furostanol glycoside as if Marker degradation took place in plant body. Representative these unusual novel compounds obtained in this time would provide additional important new pathways, route-A and route-B, for steroidal biogenesis.

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We screened the differentiation-inducing activities of 39 mushroom extracts from Akita prefecture, Japan, on the mouse osteoblastic cell line, MC3T3-1. Sixteen phosphate buffered saline (PBS), 8 boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MC3T3-1 cell differentiation. The enzyme activities were markedly induced by extracts of Tricholoma auratum, and we isolated the active compound from methanol extracts of this mushroom. Physical data for the isolated active compound were identical to those for (,24R)-ergosta-7,-diene-3β,,6β-triol (1). 1 induced ALP activities of MC3T3-1 cells and promoted cell proliferation. To investigate the relationships between the chemical structure and differentiation-inducing activity of the compound, ALP-inducing activities of MC3T3-1 cells by 1, ergosterol (2), ergocalciferol (3), cholesta-3β,,6β-triol (), 7-dehydrocholesterol () and cholecalciferol (6) were tested. The enzyme activities of MC3T3-1 cells were increased 3.0-fold by 10 μM 1 and 2.-fold by 10 μM . However, 2, 3, and 6 did not induce MC3T3-1 cell ALP activity at 0.1—10 μM. These results suggested that the OH groups at C- and/or C-6 of 1 and played an important role in their differentiation-inducing activities on MC3T3-1 cells. Furthermore, 1 suppressed induction of MC3T3-1 cell apoptosis by serum starvation.

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Approximately 99% of the fat in huma milk is secreted into the alveoli by the mammary secretory epithelial cell (lactocyte) in membrane bound milk fat globules (MFG). The MFG, unlike small molecules such as lactose, have little effect on the osmotic balance between milk and blood and therefore they can be stored in large amounts in the alveolar lumen.Approximately % of the fat in the MFG are tri-acylglycerols (TAG). Importantly, different species, . g. women, rabbits, cows and elephants, have distinctive combinations of fatty acids esterified as TAG in their milk.We have measured 24-h milk production, fat content and fatty acid composition at 1, 2, , 6, 9, and 12 months of lactation in women.Mean (±SD) milk production (375.-1: 153.mL/24-h/breast) differed between breasts, between women and with stage of lactation (p<0.05). Whereas the fat content (35.±7.86g/L) and the percentage composition of 18: 1n9 (32.24±3.3), 18: 2n6 (9.18±2.66), 18: 3n3 (0.76±0.21), 20: n6 (0.37±0.07), : n3 (0.17±0.04), and : 6n3 (0.2±0.07) differed only between women and with stage of lactation (p<0.05).In contrast, the amount delivered to the infant differed (p<0.05) between women only for 18: 3n3, : n3 and : 6n3 and no differences in amounts delivered were observed for any of these fatty acids from 1 to 12 months of lactation.Each child received a mean (±SD) of 8.27-2. g 18: 1n9; 2.38±0.g 18: 2n6;194±73mg 18: 3n3;92±31mg 20: n6;43±14 mg : n3 and 49±21 mg : 6n3 every 24-h from breastmilk over the first year of life.These results indicate that variation in percentage composition of individual fatty acids (.g.18: 2n6) does not always translate to variation in the amount delivered to the infant.
Milk fat not only accounts for approximately 50% of the infant's energy intake, but also is responsible for the supply of the essential and long-chain polyunsaturated fatty acids that are required for the optimal development of the infant.For example, arachidonic acid (20: n6) and eicosapentaenoic acid (20: n3) are essential precursors for the synthesis of prostaglandins and immunomodulatory eicosanoids.On the other hand, docosahexaenoic acid (: 6n3, DHA) is a major polyunsaturated fatty acid in the membranes of the cerebral cortex and retina and higher intakes of DHA have been associated with higher ratings in intelligence tests particularly in children born prematurely. Fatty acids and mono-acylglycerols released by hydrolysis of TAG in the infant's digestive tract have a detergent like lytic action and inactivate enveloped viruses, gram positive and gram negative bacteria, fungi and protozoa.The membrane surrounding the human MFG contains mucin filaments that may act as a decoy to pathogenic micro-organisms ( coli).Micro-organisms recognise mucin filaments as membrane docking sites from which to launch an invasive infection and are thereby lured away from the membrane docking sites on the epithelial cells lining the infant's digestive tract.
Despite the importance of milk fat to the infant, it is the most variable component of human milk.It varies, over the course of a feed, over the course of the day, with stage of lactation, from one lactation to the next, between breasts, and between women. The major predictors of the fat content of milk over the course of a day have been shown to be the length of the interval between breastfeeds, the fat content at the end of the previous breastfeed, the amount of milk removed at the previous breastfeed and the amount of milk removed at the current feed.However, we have found that the fat content of milk is determined primarily by the amount of milk (degree of fullness) in the breast.For example, if the baby sleeps overnight, the mother's breasts will be full of milk in the morning and the fat content of fore-milk (milk obtained before a breastfeed) will be very low.

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Objective: Our objective was to evaluate the mechanism of atrial tachycardia (AT) induced by atrial pacing using EnSite NavX multi-electrode mapping system after extensive encircling pulmonary vein isolation (EEPVI) for the paroxysmal atrial fibrillation (). Methods: We evaluated 100 consecutive paroxysmal patients undergoing EEPVI (all were first procedures, age 60±11 years, 66 males, LA diameter 34± mm). Rapid atrial pacing up to 170 ms was performed to induce or AT after EEPVI. Activation mapping of induced AT was performed using EnSite NavX. Results: EEPVI was completed in all patients. After EEPVI, was induced in 13 patients and AT was induced in 31 patients (34 AT). Atrial activation sequences of 27 AT were evaluated. In the 27 AT, (81%) were macro-reentrant AT and (19%) were focal AT. In the macro-reentrant AT, 11 were peri-mitral AT with a cycle length (CL) of 200±25 ms, were roof-dependent AT (CL 202±56 ms, 3 around left PV and 2 around right PV) and 6 were atrial flutter around tricuspid annulus (CL 212± ms). Conclusions: Majority of AT induced by atrial pacing after the completion of EEPVI are macro-reentrant AT. Three reentrant circuits, i.., around mitral valve, tricuspid valve and pulmonary vein, relate with maintenance of the macro-reentrant AT.

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Chemical synthesis of (, 24R)- and (, 24S)-1, 24-dihydroxy--vitamin D₃ has been achieved starting with the commercially available dinorcholenic acid acetate. Synthesis involved introduction of the 1-hydroxy group by a reduction of the 1, 2-epoxide generated by epoxidation of the 1, , 6-trien-3-one. The side chain on the steroid was then constructed by means of a Wittig reaction followed by introduction of the Δ⁷ bond by standard methods and its protection with 1-phenyl-1, 2, -triazoline-3, -dione. Subsequent reduction of the hydroxy groups in the steroid side chain followed by reduction of the Diels-Alder addition products yielded the both 24-isomers. The , 7-dienes were irradiated and the corresponding vitamin D compounds isolated. Nuclear magnetic resonance was used to identify individual isomers. The (, 24S)-1, 24-hydroxyvitamin D₃ compound bound equally well to the chick intestinal cytosol receptor as 1, 25-dihydroxyvitamin D₃, while the 24R-isomer was approximately ten times less active. In vivo, both isomers were less active than 1, 25-dihydroxyvitamin D₃ ; however, the 24S-isomer was considerably more active than the 24R-isomer approaching the activity of 1, 25-dihydroxyvitamin D₃.

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Backgrounds: We evaluated that electrophysiological characteristics and clinical outcomes of atrial fibrillation () with sinus node dysfunction (SND) after radiofrequency catheter ablation (RFCA). Methods: Among 428 patients (male, 77.3%; 56.0±11.0 years old; paroxysmal , 69.%) who underwent RFCA for , 50 patients (11.7%) who had ECG documented symptomatic SND (28 Tachybrady (T-Bs) and sick sinus syndrome; SSS) were compared with 378 patients without SND. Results: 1. The patients with SND were older (60.3±61617; 9.7 vs. 55.±61617; 11.1 years, p=0.003) and had higher /′ (12.±61617; .1 vs. 9.9±61617; .1, p=0.002) than those without SND. 2. Effective refractory period (ERP) at high right atrium (RA) was longer (ERP; 244.1±61617; 26.1 vs. 232.2±61617; 28.2 ms, p=0.033) and endocardial voltage at posterior left atrium (LA) was higher (1.2±61617; 0.8 vs. 0.9±61617; 0.8 mV, p=0.041) in patients with SND than those without it. 3. The recurrence rate was not different significantly between groups (28.0% vs. 20.0%, p=0.623) during 12.7±.9 months. A patient with SSS (.%) and a patient with T-Bs (3.6%) were implanted pacemaker because of recurrent symptomatic bradycardia after RFCA. Conclusion: is associated with SND more often in patients with old age, diastolic dysfunction, and high RA ERP. RFCA results in comparable clinical outcome in those patients, but % of them required pacemaker implantation due to recurrence and symptomatic bradycardia.

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要旨：維持血液透析（HD）患者における運動誘発性ゼロTBI サイン（-ZETS）の有用性は不明である。そこでHD 患者において安静時にゼロTBI サインを認めた 趾（r-ZETS 群），-ZETS が出現した 趾（-ZETS 群）および-ZETS が出現しなかった63 趾（非-ZETS 群）の臨床所見および予後を比較した。-ZETS 群の下肢血行動態は，r-ZETS 群と非-ZETS 群の中間的位置にあった。また，36 カ月間の追跡調査の結果，-ZETS 群はr-ZETS への移行を回避する率（63.6％）が，非-ZETS 群（.％）より顕著に低かった（p<0.001）。HD 患者の-ZETS はr-ZETS に先行して現れ，足趾の高度な灌流障害の予兆として有用であると考えられた。

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Backgrounds: It has been reported that somatic mutations of mitochondrial DNA (mtDNA) is related with aging, or development of cardiovascular disease. We hypothesized that mtDNA4977 deletion mutation (4977-) detected from human blood contributes to atrial dysfunction in patients with . Methods: We studied for mtDNA4977- in 183 patients with non-valvular , (127 PAF, 56 PeAF) and 69 patients with healthy control. The detection of mtDNA4977- was determined by Gene Scan. Results: 1. The mtDNA4977- in patients were older than those without mutation (61.±9.2 vs. 51.8±9.9, p<0.0001). 2. Frequency of mtDNA4977- mutation in patients with ≤45 years old was not different to age matched control (7.3% vs. 11.6%, p=0.2371). 3. The mtDNA4977- had higher /, (11.3±.8 vs. 9.1±3.1, p=0.0005), plasma levels of TIMP-1 (1.51±0.77 vs. 1.28±0.57 ng/mL, p=0.0210) and ANP (3.11±2.67 vs. 1.91±2.01 nmole/L, p=0.0010), and were more frequently taking statin (27.2% vs. .%, p=0.0055) than those without mutation. . 82.3% with mtDNA4977- and 85.% without mtDNA4977- remain in sinus rhythm 12.7±.9 months after RFCA (p=0.3008). Conclusion: mtDNA4977- was related with aging, diastolic dysfunction, serologic markers related with atrial remodeling or pressure overloading. Its frequency was not different to age matched patients with control, and did not affect the clinical outcome after RFCA.

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Distribution of bacteria which produce enzyme capable of lysing Str. mutans 49 strain in human dental plaques was investigated on adults of age 20 to . The activity of the enzyme (MLE) produced by an isolated strain (FDC-63) was also investigated. The results obtained are summarized as follows. 1. MLE producing bacteria were detected in 43 samples (37.1%) out of 116 samples of dental plaques obtained from adults of age 20 to . 2. Twenty four samples had MLE producing bacteria at the rate of over % of total number of bacteria in each sample. 3. The 40 strains isolated were composed of 92.% of Gram positive cocci, 2.% of Gram negative cocci and % of Gram positive rods. . Most of the isolates (.6%) showed lytic activity against living cells of 49 on GAM agar plates. . The MLE produced by FDC-63 had lytic activity against both living and heat killed cells of 49 under aerobic or anaerobic condition. 6. The activity of the MLE was rather weak against purified cell walls of 49. 7. Optimal pH in the activity of the MLE was 6.0 and optimal temperature 37℃. The activity of the MLE was lost by heating at 60℃ for 60 min. 8. FDC-63 was identified as Streptococcus milleri.

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Background:The relationship between outcome of radiofrequency catheter ablation (RFCA) for atrial fibrillation () and the severity of left ventricular (LV) diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM) remains unknown.Methods and Results:Twenty-two HCM patients (12 female, aged 65±11 years) with paroxysmal (n=; 23%) or persistent (n=17; 77%) were enrolled. LV diastolic function was evaluated according to the ratio of the mitral inflow early filling velocity to the velocity of the early medial mitral annular ascent (/’) measured on pulsed wave and tissue Doppler assessments in all patients. Pulmonary vein isolation was performed in all patients. A second procedure was performed in 3 patients. During a follow-up of 21±12 months, sinus rhythm was maintained in 13 of patients (59%). /’ was significantly higher in the patients with recurrence than in those without (18±7 vs. 11±3; P<0.01). On Kaplan-Meier analysis the prevalence of recurrence was significantly higher in patients with /’ ≥15 (n=6) than in those with /’ <15 (n=16; P<0.01). On multivariate Cox regression analysis the only significant and independent predictor for recurrence was /’ (hazard ratio, 1.16; 95% confidence interval: 1.01–1.37, P=0.03).Conclusions:LV diastolic dysfunction evaluated using /’ was associated with difficulty of rhythm control after RFCA in patients with HCM and . (Circ J 2015; 79: 419–424)

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ブドウの雌性台木3品種(いずれも二倍体)'Millardet et de Grasset 101-14'〔以下'101-14' (2x),Vitis riparia Michx × V. rupestris Scheele〕および'Millardet de Grasset 41B'〔以下'41B' (2x), V. berlandieri Planch. × V. vinifera L.〕'Kober ' 〔以下''(2x), V. berlandieri × V. riparia〕に雄性台木品種'Teleki C' (V. berlandieri × V. riparia)の四倍体〔以下'C' (x)〕を交配し,未熟種子から取り出した胚の培養を行った.これら3種類の交配組み合わせにおいて得られた胚のほとんどは球状胚あるいは異常または不定型な形状の胚であった.'101-14' (2x)×'C' (x), '41B' (2x)×'C' (x),および'' (2x)×'C' (x)の交配から得られたこのような胚から,それぞれ3,2,個体の三倍体を得た.これらの三倍体のうぢ' (2x)と'C' (x)の交配による1系統(以下-1 (3x))において順化期間中での生育特性を'' (2x)および'' (x)を対照として調査した.-1(3x)における新梢および根の生長ならびに葉の形態は'' (2x)と'' (x)の中間となった.-1(3x), ''(2x)および'' (x)に試験管内接ぎ木した'巨峰'(V. × labruscana Bailey)の順化期間中の生育を比較した.穂木の新梢生長および根の生長は'' (2x)台木で最も大きく,次いで-1(3x)台木,'' (x)台木で最も小さくなった.根の先端部切片とフィロキセラ(Daktulosphairae Fitch)との共存培養において, -1(3x)および'' (x)は優れたフィロキセラ抵抗性を示した.

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Due to specific adsorption to variable charge soils, low molecular weight organic acids (LMWOAs) have not been sufficiently extracted, even if common extractants, such as water and 0.1 M sodium hydroxide (NaOH), were employed. In this work, the method for extracting LMWOAs in soils with 0.1 M NaOH was improved for variable charge soils;

e

.g. 1.0 M potassium fluoride (KF) with pH .0 was applied as an extractant jointed with 0.1 M NaOH based on its stronger ability to change the electrochemical properties of variable charge soils by specific adsorption. With the proposed method, the recoveries of oxalic, tartaric, malic, citric and fumaric acids were increased from 83 ± , 93 ± 1, ± 2, 63 ± and ± 3% to ± 2, 100 ± 2, 85 ± 2, 90 ± 2 and 89 ± 2%, respectively, compared with NaOH alone. Simultaneously, the LMWOAs in Agri-Udic Ferrosol with field moisture were measured with a satisfactory result.

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