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. Ca. cells were transfected with a metallothionein-inducible 1 expression vector (Ca.MTF) to investigate the relationship between invasive ability and cell cycle modulation caused by 1. MMP- and p21^waf1/cip1 protein were synergistically increased in the stimulated CA.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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Effect of an antirheumatic gold compound, Auranofin (

), have been revealed.  1-10 µM of inhibited prostaglandin () production and nitric oxide (NO) production in macrophages treated with some stimulatory compounds.  We found that reduced cyclooxygenase (COX)- 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 production was almost completely inhibited.

  In the review on manuscripts,

is reported to down-regulate the mRNA levels of SLC47A1, , ATP1A3, , , PIK3CA, and up-regulate the mRNA levels of ABCC3, ABCB1, , , , CLTD, CLTB.  PGs are known to be transported by 4 transporters, OATP-PG (SLCA), SLC21A (OATPA1, SLCO), SLC21A11 (OATP3A1), and ABCC4, though I could not identify whether reduced concentration in cellular cultured medium as described above via these transporters by downregulation for export of .

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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 -, 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 - 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 - 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-, for steroidal biogenesis.

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A full account is given of the chemical behavior observed for 7, -dialkyladeninium salts (16). On treatment with boiling 1N aqueous NaOH for 60min, 16a, , d, (X=I), 16c (X=Br), and 16f (X=ClO₄) rearranged to isomeric N⁶, 7-dialkyladenines (21a-f) in 50-91% yields. Treatment of the salts with 0.N aqueous at room temperature for 30-90min or with Amberlite CG-400 (OH^-) in at room temperature gave the ring-opened derivatives a-f (in the trans-formamide form) in 56-83% yields, and rate constants for the ring-opening reactions of 16a, , d-g (X=ClO₄) and 16c (X=Br) leading to a-g were determined in at pH . and ionic strength 0.50 at 25°C. Cyclization of a with NaH in at room temperature or with boiling 1N aqueous NaOH produced 21a in % or 72% yield, respectively.In solution, the trans-formamides seemed to transform slowly into the cis-formamides 23, attaining equilibria. The existence of such an equilibrium in or -d₆ at 25°C or in at pH . and ionic strength 0.50 at 25°C was kinetically confirmed in the case of a, and the mechanism of the rearrangement of 16 to 21 through is discussed on the basis of the above kinetic results and Deslongchamps' theory of stereoelectronic control. On treatment with NaBH₄ in MeOH at room temperature, 16a (X=I) furnished the 7, 8-dihydro derivative 28 (% yield), which slowly decomposed in at 60°C to give a in 49% yield.The 7, -dialkyladeninium salts (16) were found to be obtainable from N'-alkoxy-1-alkyl--formamidoimidazole-4-carboxamidines () through an alternative synthetic route : Alkylations of with alkyl halides in in the absence of base, followed by hydrogenolysis of the N'-alkoxy group and cyclizatio (or vice versa) produced 16 in acceptable yields. In order to interpret the proton nuclear magnetic resonance spectrum of a, the -deuterated species 26 was also synthesized from 24 via 25 and 27.

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Background: The dissociated activities (DAs) indicates arrhythmogenicity of the isolated PV after the pulmonary vein isolation (PVI) for atrial fibrillation (). We investigated its impact on recurrence after the PVI. Methods: The subjects were paroxysmal patients (age: 55±, 71 males) who had recurrence after PVI and underwent the repeat procedure. All patients were divided into two groups regarding to the presence/absence of DAs during the first procedure (group A: DAs in ≥1PV, group : no DA). Results: Group A and consisted of 62 and patients, respectively. In the repeat session, the number of reconnected PVs was similar between the two groups (203/246 (83%) PVs vs. 69/87 (79%) PVs, P=0.61). The mean age was significantly higher (60±8 vs. 54±11 years, P<0.01) and non-PV ectopic foci were more frequently observed (68% (15/) vs. 29% (18/62), P=0.003) in group compared to group A. Additionally, 73% (11/15) of patients of group demonstrated ectopic beats from superior vena cava (SVC). Conclusions: Absence of DAs after PVI might indicate the presence of concealed non-PV foci initiating in paroxysmal patients. Supplemental SVC isolation should be considered in cases without DAs in PVs during the first procedure.

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The gamma-ray spectrum and the conversion-electron spectrum are measured in the decay of the ^116mIn activity. Directional correlations are also measured for 818–1293 and 1097–1293 keV cascades. The M1- mixing ratio δ, and the 0- mixing ratio μ_k are obtained for 818.7 keV +→2₁⁺ transition to be δ=1.52−

0.22

+0.26, and μ_k≤6.1×10⁻⁴ respectively. The

E

2

branching ratio

B

(

E

2

;

2₂

+→0_g⁺):

B

(

E

2

;

2₂

+→2₁⁺):

B

(

E

2

;

2₂

+→0₁⁺) is determined to be 0.0158:1.0:

5

.86.

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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 + on the lipid/protein interaction were studied. Following + 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 % of lipid once disturbed by the adsorption of glycophorin head groups is decoupled after addition of +. 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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The gamma-ray spectrum and the conversion-electron spectrum are measured in the decay of the Tb¹⁵² activity. The L-subshell electron lines of the 586.7 keV +→2₁⁺ transition are separated by the ion-free beta-ray spectrometer. The M1- mixing ratio, , and the dimensionless ratio X of 0- mixing of the 586.7 keV transition are obtained to be ≤0.16 and 0.034≤X≤0.038, respectively. The branching ratio (; +→0_g⁺): (; +→2₁⁺): (; +→0₁⁺) is determined to be 0.023 : 1.0 : .6.

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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: 1. The patients with SND were older (60.3±61617; .7 vs. 55.4±61617; 11.1 years, p=0.003) and had higher /′ (12.4±61617; .1 vs. .±61617; 4.1, p=0.002) than those without SND. . Effective refractory period (ERP) at high right atrium (RA) was longer (ERP; 244.1±61617; 26.1 vs. 232.±61617; 28. ms, p=0.033) and endocardial voltage at posterior left atrium (LA) was higher (1.±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: 1. The mtDNA4977- in patients were older than those without mutation (61.4±. vs. 51.8±., p<0.0001). . 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. .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±.67 vs. 1.91±.01 nmole/L, p=0.0010), and were more frequently taking statin (27.% 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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This study aimed to determine the prevalence of fecal carriage of extended spectrum β-lactamase (ESBL) and/or plasmidic AmpC β-lactamase (pAmpC) producing Escherichia coli among dogs (n=428) in Turkey. Polymerase chain reaction (PCR) and sequencing were used to characterize genes encoding β-lactamase and plasmid mediated quinolone resistance (PMQR). Antimicrobial susceptibility testing and PCRs for virulence genes and phylogenetic groups were also performed. Cefotaxime resistant

. coli isolates were detected in 95 (.%) of the swab samples. Sequencing analysis results showed occurrence of various β-lactamase genes: bla_CTX-M-15 (62), blaTEM-

1b

(42), blaCMY-

2

(

22

), bla_CTX-M-3 (16), bla_CTX-M-1 (15), bla_OXA-1 (

9

) and bla_SHV-12 (3) alone or in combination. The most frequently encountered phylogenetic group was group A₁ (35.8%), followed by group

D₂

(

22

.1%),

B

1 (15.8%), D₁ (

9

.

5

%), A₀ (7.4%),

B2₂

(

5

.3%) and

B2₃

(4.

2

%), respectively. PMQR genes, aac(6’)-Ib-cr, qnrS1 and qnrB10 were detected in 25.3, 10.

5

and 1.1% of the isolates, respectively. While all isolates were susceptible to imipenem and amikacin, resistance rates to non-β-lactam antibiotics ranged from 20.0% for tobramycin to 56.8% for tetracycline. The virulence genes were only detected in 34 (36.

2

%) of the isolates and this isolates carried single or various combination of virulence genes of iucD, papC, papE, f17a-A and eaeA. Four isolates were identified as human virulent pandemic CTX-M-15 producing

E

. coli clone O25

b

:ST131/

B

2

. To the best of our knowledge, this is the first study to show fecal carriage of ESBL/pAmpC type β-lactamase producing

E

. coli isolates among dogs in Turkey.

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The phase diagrams of the Ni-Mo- and Ni-W- ternary systems in the region of less than 50mol% were constructed by thermodynamic calculation, based on the data obtained by thermodynamic measurement of the related materials. We found three ternary eutectic points and three or two ternary peritecto-eutectic points as follows:
:L (1365K, 71.mol%Ni-6.0mol%Mo-.mol%)=(Ni)++
:L (1355K, 62.mol%Ni-.mol%Mo-30.mol%)=++
:L (1445K, 42.0mol%Ni-30.6mol%Mo-10.3mol%)=(Ni)+NiMo+
P₁:L (1812K, 34.mol%Ni-42.3mol%Mo-.8mol%)+MoB=+
:L (1633K, 42.3mol%Ni-40.4mol%Mo-17.3mol%)+Mo=+
P₃:L (1812K, 53.mol%Ni-33.7mol%Mo-12.8mol%)+Mo=NiMo+
:L (1622K, 51.0mol%Ni-31.6mol%W-17.4mol%)=(Ni)+W+
:L (1260K, 71.0mol%Ni-7.0mol%W-.0mol%)=(Ni)++
:L (1291K, 65.4mol%Ni-4.8mol%W-29.8mol%)=++
P₁:L (2115K, 23.8mol%Ni-43.1mol%W-33.1mol%)+WB=+
:L (1657K, 48.mol%Ni-33.1mol%W-18.0mol%)+=W+
The calculated phase diagrams are expected to be useful for the development of new Ni-based heat-, corrosion- or wear-resistance alloys.

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Background: Strokes can develop in patients with atrial fibrillation () having low CHADs score. We aimed to clarify the characteristics of left atrial appendages (LAAs) in non-valvular stroke patients with low CHADs score.
Methods and Results: A total of 333 patients (paroxysmal: n=222) who underwent computed tomography (CT) and ablation were examined, out of whom 29 patients (8.7%) had strokes ( males, 60± yo, paroxysmal). The average CHADs score at the onset of stroke was 0.6±0.6, the size of left atrium was 3.±0. cm and the blood flow velocity of LAA was 51± cm/sec. LAA anatomy was classified into 4 types of morphologies: “Cauliflower”, “Windsock”, “Cactus”, and “Chickenwing”, and the distribution was compared with 51 age and sex matched control. Comparing stroke group vs. control group, Cauliflower was 69% vs. 31%, Windsock was 19% vs. 31%, Chickenwing was 4% vs. % and Cactus was 4% vs. 31%, respectively. Regarding the position of the LAA, lower position of LAA orifice than the left superior pulmonary veins were more common in stroke patients (stroke vs. control; 12 (%) vs. 16 (31%), respectively.
Conclusion: patients with low CHADs score and strokes had well-lobulated and lower positioned LAA. The anatomy of LAAs might be helpful to identify risks for strokes.

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Brassinolide analogues, (R, 23R, 24R)-, 3α, , 23-tetrahydroxy--homo-7-oxa--ergostan-6-one (24-epibrassinolide) (10) and (S, 23S, 24R)-, 3α, , 23-tetrahydroxy--homo-7-oxa--ergostan-6-one (), were synthesized from brassicasterol (3a) in five steps and with ca. 20% overall yield. The key steps are the direct formation of (, 24R)-3α, -cyclo--ergost--en-6-one (4) from brassicasterol mesylate (3), the acid-catalyzed rearrangement of 4 to (, 24R)--ergosta-, -dien-6-one (6), and the Baeyer-Villiger oxidation of the tetrahydroxy -ergostan-6-ones 7 and 8.

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厚生省の高齢者の聴力に関する研究班は65歳以上の高齢者の聴力を調査した. 測定7周波数の平均聴力レベルはA群 (65～69歳) で35.0dB, 群 (70～74歳) で42.1dB, C群 (75～79歳) で46. 1dB, D群 (～歳) で52. 1dB, 群 (85歳以上) で55.6dBであった. すべてのグループにおいて聴力の男女差はみられず, オージオグラムの型は大部分の例で高音漸傾型を示した. 平均語音弁別能はA群で75.4%, 群で70%, C群で63.8%, D群で59.7%, 群で52.1%, また, SISI検査で70%以上を示した率はA群で45.%, 群で49.3%, C群で47.%, D群で51.6%, 群で59.7%であった.

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