, 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 positively regulates transcription from the / promoter. Ca. cells were transfected with a metallothionein-inducible expression vector (Ca.MTF) to investigate the relationship between invasive ability and cell cycle modulation caused by . MMP- and / protein were synergistically increased in the ZnCl₂ stimulated CA.MTF cells, and both proteins were identified in the same cells when was induced. These results imply that invasive growth of tumor cells occurs in the static state of the cell cycle and that plays a key role in this phenomenon.

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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-. Sixteen phosphate buffered saline (PBS), 8 boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MC3T3- 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 (). induced ALP activities of MC3T3- 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- cells by , ergosterol (2), ergocalciferol (3), cholesta-3β,,6β-triol (4), 7-dehydrocholesterol () and cholecalciferol (6) were tested. The enzyme activities of MC3T3- cells were increased 3.0-fold by 10 μM and 2.4-fold by 10 μM 4. However, 2, 3, and 6 did not induce MC3T3- cell ALP activity at 0.—10 μM. These results suggested that the OH groups at C- and/or C-6 of and 4 played an important role in their differentiation-inducing activities on MC3T3- cells. Furthermore, suppressed induction of MC3T3- cell apoptosis by serum starvation.

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Effect of an antirheumatic gold compound, Auranofin (

), have been revealed.  -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 , , , ABCG2, , PIK3CA, and up-regulate the mRNA levels of ABCC3, , , ABCC2, SLC31A2, CLTD, CLTB.  PGs are known to be transported by 4 transporters, OATP-PG (SLCA), SLC21A2 (OATP2A, SLCO2), SLC21A11 (OATP3A), and ABCC4, 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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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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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 , 69.4%) 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: . The patients with SND were older (60.3±61617; .7 vs. 55.4±61617; 11. years, p=0.003) and had higher /′ (12.4±61617; . vs. .±61617; 4., p=0.002) than those without SND. 2. Effective refractory period (ERP) at high right atrium (RA) was longer (ERP; 244.±61617; 26. vs. 232.2±61617; 28.2 ms, p=0.033) and endocardial voltage at posterior left atrium (LA) was higher (.2±61617; 0.8 vs. 0.±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±. months. A patient with SSS (4.%) 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 4% of them required pacemaker implantation due to recurrence and symptomatic bradycardia.

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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: . The mtDNA4977- in patients were older than those without mutation (61.4±.2 vs. 51.8±., 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±4.8 vs. .±3., p=0.0005), plasma levels of TIMP- (.51±0.77 vs. .28±0.57 ng/mL, p=0.0210) and ANP (3.11±2.67 vs. .91±2.01 nmole/L, p=0.0010), and were more frequently taking statin (27.2% vs. .4%, p=0.0055) than those without mutation. 4. 82.3% with mtDNA4977- and 85.% without mtDNA4977- remain in sinus rhythm 12.7±. 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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Chemical synthesis of (, 24R)- and (, 24S)-, 24-dihydroxy--vitamin D₃ has been achieved starting with the commercially available dinorcholenic acid acetate. Synthesis involved introduction of the -hydroxy group by a reduction of the , 2-epoxide generated by epoxidation of the , 4, 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 -phenyl-, 2, 4-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)-, 24-hydroxyvitamin D₃ compound bound equally well to the chick intestinal cytosol receptor as , 25-dihydroxyvitamin D₃, while the 24R-isomer was approximately ten times less active. In vivo, both isomers were less active than , 25-dihydroxyvitamin D₃ ; however, the 24S-isomer was considerably more active than the 24R-isomer approaching the activity of , 25-dihydroxyvitamin D₃.

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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- 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- 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- and -2 were assumed to be isomers at C-23. The structure of -a- 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- 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-4(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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The acetone extracts from three samples of the hepatopancreas of the poisonous scallops obtained on the Okhotsk Coast of Hokkaido Island were fractionated into two parts, hexane soluble fraction (fraction H) and 85% aqueous ethanol soluble fraction (fraction ) by partition to two layers. The majortoxic components in the mouse assay of “diarrheic shellfish toxin” by intra-peritoneal injection were found to be free unsaturated fatty acids showed the following toxicity in MU per g, 18: n- 35, 18:2 n-6 , 18:3 n-3 167, 18:4 n-3 , 20: n-3 167, and :6 n-3 , respectively. Toxicity of the fraction Hin MUper g was much lower than that of the fraction . However, the toxicity of the fraction H per g of the hepatopancreas was about twice that of the fraction , since the fraction Hwas much more abundant than the fraction in the hepatopancreas. The method for the assay of the diarrhetic shellfish toxin must be reexamined by considering the toxic effect of the free unsaturated fatty acids.

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The effects of the pressure of ambient gas and sample temperature on photo-acoustic displacement (PAD) were studied quantitatively using an extremely sensitive laser interferometric probe. For silicon, the PAD signal measured at atmospheric pressure increased by about 18% as compared to that obtained in a vacuum, and varied by less than 0.7% for a change in pressure of % around atm. This effect was attributed to the decrease in refractive index of the gas adjacent to the sample. Temperature rise caused PAD to increase proportionally, and for GaAs, PAD varied 0.4% per degree. The variation of PAD with temperature was accurately explained by the temperature dependence of thermal expansion coefficient and thermal conductivity of the sample.

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The numerical values of the intervals betrween optieal levels are competed for the configurations *⁹4s, s, 6s and 7s of Cu⁺, according to the general expression of energy-levels derived in the previous paper The self-consistent field radial functions computed by Hartree adn Hartree are used fors, 2s, 2p, 3s, 3p and 3d. Those of 4s, s, .s and are ealenlated from Hartree Hartree's core-functions by the numerical integrations. The calculated results are shown in Table I.The agreement with experiment is satisfactory

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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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