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Purpose The aims of the present study were to investigate the symptom clusters in terminally ill patients with cancer using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL), and to examine whether these symptom clusters influenced prognosis. Methods We analyzed data from 130 cancer patients hospitalized in the palliative care unit from June 2018 to December 2019 in an observational study. Principal component analysis was used to detect symptom clusters using the scored date of 14 items in the QLQ-C15-PAL, except for overall QOL, at the time of hospitalization. The influence of the existence of these symptom clusters and Palliative Performance Scale (PPS) on survival was analyzed by Cox proportional hazards regression analysis, and survival curves were compared between the groups with or without existing corresponding symptom clusters using the log-rank test. Results The following symptom clusters were identified: cluster 1 (pain, insomnia, emotional functioning), cluster 2 (dyspnea, appetite loss, fatigue, and nausea), and cluster 3 (physical functioning). Cronbach’s alpha values for the symptom clusters ranged from 0.72 to 0.82. An increased risk of death was significantly associated with the existence of cluster 2 and poor PPS (log-rank test, p = 0.016 and p Conclusion In terminally ill patients with cancer, three symptom clusters were detected based on QLQ-C15-PAL scores. Poor PPS and the presence of symptom cluster that includes dyspnea, appetite loss, fatigue, and nausea indicated poor prognosis.

A series of bis-cycloheptatrienyl triangular triplatinum complexes are synthesized as a novel class of organoplatinum sandwich compounds. The tris-ethylene triplatinum sandwich complex and the monophenyl bis-ethylene sandwich complex of triangular triplatinum are structurally characterized by X-ray crystallographic analyses. The net assembling of three Pt0 atoms between two tropylium cations is initiated by complexation of a Pt0 moiety by a tropylium ligand, where the mononuclear cycloheptatrienyl PtII intermediate is detectable in situ by NMR. It is revealed that the choice of added ligands is crucial to the efficient formation as well as conversion of the key mononuclear cycloheptatrienyl PtII intermediate.

The reaction of a substitutionally labile dipalladium(I) complex [Pd2(CH3CN)6][BF4]2 (1) with 1,3,5,7-cyclooctatetraene (COT) in acetonitrile afforded [Pd2(μ-η3:η3-C8H8)(CH3CN)4][BF4]2 (2). The reaction of 2 with COT in acetonitrile yielded [Pd2(μ-η3:η3-C16H16)(CH3CN)4][BF4]2 (4), where COT is dimerized via C–C bond formation. Complexes 2 and 4 were structurally characterized by X-ray diffraction analyses. In dichloromethane, COT isomerized to styrene at room temperature in the presence of catalytic amount of 1, 2, or 4.

We studied the improvement of the detect-ability of lymph node (LN) metastases from colorectal cancer in 18F-fluorodeoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) by analyzing the acquired counts with a statistical method. Thirty-nine metastatic LNs from 32 cases with colorectal cancer were included in this study. “Uptake region” was defined as the site where counts were higher than the average plus 3 standard deviations (SDs) on each transaxial image of FDG PET. After the initial uptake regions were selected, these high accumulation areas were automatically excluded from consideration thereafter. This method was repeated and new uptake regions were identified. This method was repeated up to five times. After that, the stacked-up uptake regions were compared with computed tomography (CT) images, and the high accumulation areas that were superimposed on the normal structures, such as intestine, vessels, and ureters, were excluded from the consideration. The remaining uptake regions were diagnosed as metastatic LNs, and the detectability of LN metastases was calculated. We then compared these statistical results with the results obtained on the basis of visual assessments by radiologists. Our proposed method showed the best results when the procedures were repeated three times in the light of detectability. After being repeated three times, this method detected 15/23 (65.2%) metastatic LNs in the first LN group, 16/16 (100%) in the second-third LN groups and 31/39 (79.4%) in the total LNs, whereas the radiologists diagnosed 8/23 (34.8%) of metastatic first LNs, 12/16 (75.0%) in the second-third LNs and 20/39 (51.3%) in the total LNs. A statistically significant difference was observed between the result of iteration number 3 and that by radiologists as for the second—third LNs and the total LNs. This study suggests that our proposed statistical method could improve the detectability of LN metastases from colorectal cancer. Our method will help radiologists to detect small metastatic lesions such as LN metastases.

Objective: Diacylglycerol (DAG)-rich oil has been suggested to suppress postprandial hyperlipidemia and promote negative caloric balance by increasing energy expenditure (EE), due to small intestine physiochemical dynamics that differ from triacylglycerol (TAG). We studied the effect of DAG on postprandial glucose/insulin metabolism by loading of carbohydrate with oil. Further, to reveal the mechanism for increased EE by DAG, we measured plasma serotonin, which is mostly present in the small intestine and mediates peripheral sympathetic thermogenesis. Methods and Procedures: Randomized crossover study with 2-week wash-out interval between differing fat ingestion. Seven male, lean, Japanese students ingested DAG or TAG oil with 40 g of carbohydrate. Measurements of metabolic parameters were performed before and at 2, 4, and 6 h after fat ingestion. Plasma serotonin levels and cholesterol concentration in each lipoprotein were measured using high-performance liquid chromatography (HPLC). Results: The substitution of DAG for TAG decreased very-low-density lipoprotein-cholesterol (VLDL-C) by 45.6% at 2 h, and decreased serum insulin by 41.3% at 4 h after ingestion. The incremental area under the curve (IAUC) for VLDL-C was positively correlated with the IAUC for insulin. Concurrently, DAG elevated plasma serotonin levels by 47.3% at 2 h, while TAG did not influence. Discussion: This study indicates that the substitution of DAG for TAG suppresses the postprandial increase in serum VLDL-C and insulin. This study also demonstrates that DAG ingestion increases plasma serotonin, proposing a possible mechanism for a postprandial increase in EE by DAG.

The reaction ofN-benzenesulfonylbenzaldimine with Ni(cod)2and PCy3gave the corresponding η2-iminenickel complex quantitatively. Diphenylacetylene reacted with the η2-iminenickel complex to generate five-membered aza-nickelacycle. Insertion of second alkynes into the five-membered aza-nickelacycle led to the formation of the corresponding seven-membered aza-nickelacycles. Heating the solution of the seven-membered aza-nickelacycles induced the reductive elimination to give 1,2-dihydropyridine. In the presence of 10 mol % of Ni(cod)2and PMetBu2at 100 °C, the intermolecular [2+2+2] cycloaddition ofN-benzenesulfonylbenzaldimine and 2-butyne occurred to give the expected 1,2-dihydropyridine in 87 % yield. In the presence of PCy3, the reaction also proceeded catalytically, however, PMetBu2gave better results. Less bulky or less basic phosphine, PnBu3or P(o-tol)3, was not efficient for the reaction. Although Ni(0)-NHC complex was a good catalyst for [2+2+2] cycloaddition of two alkynes and a ketone or an aldehyde, this reaction did not proceed in the presence of an NHC ligand, 1,3-bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene.

Type 2 diabetes and dyslipidemia are cardiovascular risk factors which should be managed [1]. However, the precise lipoprotein profiles and the underlying mechanisms for diabetic dyslipidemia remain largely unknown. We previously developed an anion-exchange liquid chromatographic method (AEX-HPLC) which can measure cholesterol levels of triglyceride (TG)-rich lipoproteins such as very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and chylomicron (CM) in addition to low-density lipoprotein (LDL) and high-density lipoprotein (HDL) [2]. Here we compared lipoprotein profiles obtained by our previous studies using AEX-HPLC in young lean men [3], subjects with low Framingham risk score (FRS) [4, 5], type 2 diabetic patients without obesity and type 2 diabetic patients with obesity [6, 7]. The mean ± SD values of age, body mass index, HbA1c in in young lean men (n = 7) [3], low FRS subjects (n = 304) [4], type 2 diabetic patients without obesity (n = 194) [6], and type 2 diabetic patients with obesity (n = 5) [7] were 24 ± 2, 51 ± 8, 63 ± 13, and 60 ± 9 years old, 20.8 ± 2.2, 23.8 ± 3.0, 23.1 ± 2.0, and 29.5 ± 7.0 kg/m2, 5.0 ± 0.2, 5.4 ± 0.5, 6.3 ± 1.0, and 9.1±2.1%, respectively. HDL-cholesterol (HDL-C) in type 2 diabetes (49.9 ± 16.6 mg/dL (1.29 ± 0.43 mmol/L)), especially in type 2 diabetic patients with obesity (36.4 ± 5.3 mg/dL (0.94 ± 0.14 mmol/L)) was lower than young lean men (59.4 ± 10.1 mg/dL (1.54 ± 0.26 mmol/L)) and low FRS subjects (57.6 ± 14.7 mg/dL (1.49 ± 0.38 mmol/L)). IDL-C in type 2 diabetes was higher than other two groups, and IDL-C was higher in the order of type 2 diabetic patients with obesity (9.8 ± 3.0 mg/dL (0.25 ± 0.08 mmol/L)), type 2 diabetic patients without obesity (9.3 ± 4.6 mg/dL (0.24 ± 0.12 mmol/L)), low FRS subjects (7.3 ± 3.1 mg/ dL (0.19 ± 0.08 mmol/L)), young lean men (4.3 ± 2.2 mg/dL (0.11 ± 0.06 mmol/L)). VLDL-C clearly showed higher values in the order of type 2 diabetic patients with obesity (27.3 ± 22.7 mg/dL (0.71 ± 0.59 mmol/L)), type 2 diabetic patients without obesity (20.1 ± 16.2 mg/dL (0.52 ± 0.42 mmol/L)), low FRS subjects (16.6 ± 12.8 mg/dL (0.43 ± 0.33 mmol/L)), and young lean men (4.0 ± 4.6 mg/dL (0.10 ± 0.12 mmol/L)). LDL-C and CM-C did not show the characteristic profile for diabetes. According to accumulation of our previous AEX-HPLC data [3, 4, 6, 7], the characteristics in diabetic dyslipidemia is reduced HDL-C, and increased IDL-C and VLDL-C, which is further deteriorated by complication with obesity. Relative insulin deficiency due to insulin resistance increases activity and expression of hormone-sensitive lipase (HSL) in adipose tissue, which catalyzes the breakdown of TG, releasing free fatty acids (FFA) (Fig. 1) [8]. Insulin promotes apoB100 degradation, and hepatic insulin resistance causes reduction of apoB100 degradation [9]. Insulin resistance also induces an enhanced expression of microsomal TG transfer protein (MTP), a key enzyme involved in VLDL assembly [10]. In type 2 diabetes, increased FFA entry to liver, reduced degradation of apoB100 and enhanced expression of MTP may elevate hepatic production of VLDL. Relative insulin deficiency also decreases the activity of lipoprotein lipase (LPL), the rate-limiting enzyme of the catabolism of TG-rich lipoproteins such as CM, VLDL and IDL [11]. The formation of HDL is related with the catabolism of TG-rich lipoproteins by LPL [12]. Therefore, reduced LPL activity increases IDL and VLDL, and reduces HDL. The activity of hepatic TG lipase (HTGL), the enzyme that facilitates the catabolism of HDL, is correlated with insulin requirement [13]. In type 2 diabetes, low serum HDL-C may be partially due to an increased rate of clearance by HTGL [13]. LDL size and buoyancy are inversely proportional to HTGL activity [14], and patients with high HTGL have smaller, denser LDL particles, as compared with subjects with low HTGL activity [15]. Increased HTGL activity due Manuscript accepted for publication March 03, 2016

AIM Remnant lipoprotein is an emerging risk factor for coronary artery disease (CAD); however, the development of a specific remnant lipoprotein assay has struggled due to its heterogeneous nature. This study aimed to evaluate the clinical importance of a newly developed assay for remnant lipoprotein, RemL-C, in patients with CAD. METHODS This assay utilizes surfactant and phospholipase-D to selectively degrade and solubilize remnant lipoprotein. One hundred and sixty consecutive CAD patients who underwent coronary catheterization were recruited. RESULTS Remnant liporotein, RemL-C, was significantly higher in CAD patients (p< 0.001). Additionally, TG, hs-CRP, ICAM-1, VCAM-1, and homocysteine were significantly higher, but HDL-C and adiponectin were lower with LDL-C unchanged. Since RemL-C levels correlated with plasma TG levels, two subgroups, normotriglycedemic and normolipidemic CAD groups, were extracted. In both groups, RemL-C was still significantly higher than controls. HDL-C, but not RemL-C, was associated with the severity of CAD. RemL-C significantly correlated with TG-rich lipoproteins, in particular VLDL and IDL, when limited to normolipidemic CAD patients. CONCLUSION Remnant lipoprotein, measured by RemL-C, was increased in CAD patients independent of TG levels, indicating impaired remnant lipoprotein metabolism in these patients. CAD severity was associated with HDL-C, but not with remnant lipoprotein, indicating differential roles of lipoproteins in the development of coronary atherosclerosis. This study therefore provides clinical significance to assess coronary risk by measuring RemL-C, particularly among patients with normal TG levels.

Visible light irradiation of cis-azobenzene bridging dinuclear η6-areneruthenium complex [Ru2(η6:η1-C6H5CH2CH2CH2O)2(cis-PhN = NC6H4OMe-p)](BF4)2 in the presence of excess DMSO led to precipitation of a new dinuclear complex containing 1 equiv. DMSO ligand, [Ru2(η6:η1-C6H5CH2CH2CH2O)2(DMSO)](BF4)2 (6). A single crystal X-ray structural study of 6 revealed the presence of bridging DMSO ligand which uses O and S atoms as the donor. Treatment of 6 with 1 and 2 equiv. NaBArf (BArf = B[C6H3(CF3)2-2,5]4) afforded [Ru2(η6:η1-C6H5CH2CH2CH2O)2(DMSO)](BF4)(BArf) and [Ru2(η6:η1-C6H5CH2CH2CH2O)2(DMSO)](BArf)2, respectively, although the former was not isolated but assumed to exist only in solution by conductivity measurements. A neutral dinuclear areneruthenium complex with a bridging SO 4 2 - ligand, [Ru2(η6:η1-C6H5CH2CH2CH2O)2(SO4)] was prepared from the hydroxide [Ru2(η6:η1-C6H5CH2CH2CH2O)2(OH)]BF4 and [Et3NH](HSO4). The SO 4 2 - ion in this complex coordinates to dicationic Ru2 center rather strongly in CH2Cl2, while in MeOH the complex lies in equilibrium with a complex formed by methanolysis reaction, namely methoxy bridging dinuclear complex [Ru2(η6:η1-C6H5CH2CH2CH2O)2(OMe)]+ ( HSO 4 - ) .

The new lipoprotein analysis method using a cation-exchange chromatography, which contains a sulfopropyl-ligand column and two magnesium ion-containing eluents was previously reported. This method can separate serum lipoproteins on the column gel with a magnesium ion concentration gradient and high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) and an unspecified lipoprotein peak are eluted in order from the column. We have now characterized the unspecified lipoproteins, designated peak x, which is last eluted from the column with the eluent of high-magnesium ion concentration. The peak x was small size chylomicron fraction with a part of VLDL. Furthermore, the cholesterol values in the peak x were significantly correlated with remnant-like particle (RLP)-cholesterol values. The peak x separated from a hyperlipidemic patient included apolipoprotein B-100, B-48, E, A-1 and Cs (C-I, C-II, C-III) and its composition of free cholesterol, cholesteryl esters, triglyceride (TG) and phospholipids in total lipids were 6, 15, 66 and 13%, respectively. These results suggest that a major part of the lipoprotein peak X may be composed of remnants of chylomicron and VLDL, but it remains to be elucidated.

This review summarizes the author’s contributions to the field of chemistry of group 10 metal complexes containing unsaturated hydrocarbon ligands, with a brief introduction showing how his research subject has shifted from mononuclear type to multinuclear type complexes. New structure and reactivity trends in the multipalladium complexes with bridging allyl and allenyl/propargyl ligands, as well as bridging conjugated polyene molecules are discussed in terms of some unique bonding features of these complexes.

Reaction of η2-enone and enal-platinum(0) complexes Pt(CH2CHCOR)(PPh3)2 (R=H, Me) with Lewis acidic compounds BX3 (X=F, C6F5) afforded adducts formed by coordination of boron to oxygen of the carbonyl group. The X-ray structure determination of the adduct formed from B(C6F5)3 and η2-methylvinylketone complex showed no strong interaction between Pt and carbonyl carbon. In contrast to the inability of the palladium(0) η2-enone complexes to form any Me3Al adduct, η2-cyclohexenoneplatinum(0) complex formed an isolable adduct with Me3Al, the structure of which was also confirmed by X-ray analysis. The NMR spectral parameters (Pt–C, Pt–P and P–P coupling constants) of these adducts were compared with those of the original η2-enone or enal-platinum(0) complexes as well as the ordinary η3-allylplatinum cation [Pt(PPh3)2(MeCHCHCH2)]+.

Homoleptic olefin platinum(0) complexes, Pt(C 7 H 10 ) 3 and Pt(cod) 2 , were synthesized by the colorimetric reduction of platinum(II) complexes with SmI 2 in the presence of 2-norbornene or COD. This is a practically more convenient method for the synthesis of the Pt(0) complexes than the literature method employing Li 2 (cot).

Reaction of 1-tributylstannyl-3-chloropropene with a Pd(PPh3) species, generated in situ from Pd2(dba)3 and two equivalents of PPh3, afforded Pd(η3-Bu3SnCHCHCH2)Cl(PPh3) (1). Complex 1 underwent PPh3 promoted protodestannylation with acetic acid or diethyl malonate to give an unsubstituted η3-allylpalladium moiety as either a detectable product or a reaction intermediate. The reaction of 1 with PPh3 and 0.5 equivalent of PdCl2(PhCN)2 afforded the dinuclear complex (μ-1-3-η3:4-6-η3-CH2CHCHCHCHCH2){PdCl(PPh3)}2 (4) containing a hexatriene ligand, a formal vinylcarbene dimer.

The dinuclear Pd (I) complexes containing substitutionally labile acetonitrile ligands [Pd2 (CH3CN) 2 (L) 2] (BF4) 2 [L = CH3CN (1) , PPh3 (2) ] were prepared. The complex 1 was demonstrated to serve as a versatile building block for synthesizing sandwich chain complexes made of conjugated polyenes and linear polypalladium chains. The complex 2 reacted with 2 equiv arylacetylenes to give dinuclear organopalladium complexes arising from formal [2s + 2p + 2p] addition with the Pd-Pd s bond participating as one component. The reaction of 2 with 1,3-butadiene afforded a complex regarded as an intermediate lying halfway on the [2s + 4p] reaction coordinate.

Cycloisomerization and ring closing metathesis of some α,ω-dienes were catalyzed by a cationic arene ruthenium chelate complex [Ru{η 6 :η 1 -Ph(CH 2 ) 3 OH}(PCy 3 )Cl]BF 4 ( 1a ) in the presence of triethylamine and phenylacetylene, respectively, as co-catalysts. Analogous catalyst systems employing arene ruthenium cations without the side arm alcohol functional group showed lower efficiencies.

A novel palladium-catalyzed azathiolation of carbon monoxide using sulfenamide (RSNR‘2) (1) is described to provide thiocarbamate 2 in good yields. The mechanistic proposal includes the following: (1) insertion of CO into Pd−S bond of Pd(SR)2(PPh3)n 4 to provide Pd[C(O)SR](SR)(PPh3)n 5 and (2) σ-bond metathesis between S−N and Pd−C(O) bonds to afford 2 with the regeneration of 4.

1,3-Dienolate dipalladium(I) complex [{μ-CH2C(O)CHCH2}Pd2(PPh3)2(μ-Cl)] (2) is prepared and characterized. Complex 2 is easily protonated to yield 2-hydroxy-1,3-butadiene dipalladium(I) complex [{(μ-η2:η2-CH2C(OH)CHCH2}Pd2(PPh3)2(μ-Cl)][BF4] (3). On the basis of the comparative analyses on IR and NMR spectra and X-ray structure analysis, the co-ordination mode of 1,3-dienolate on PdPd is revealed to involve the resonance between C-bound and π-olefin-bound enolate structures.

Some insights into mechanistic features of M-C bond formation (oxidative addition) and bond cleavage (reductive elimination) about allyl-palladium complexes are presented based on new transformations of allylic as well as propargylic ligands bound to Pd and Pt. 1) The oxidative addition is proposed to proceed through initial Tc-complex formation between allylic electrophiles and M(0) atom, which is followed by intramolecular $-allyl-M bond formation with either inversion or retention of configuration at an allylic sp3-carbon depending on the nature of ligands and solvents. 2) The reductive elimination of allyl(organo)palladium complexes is suggested to proceed via cis C-C coupling between q3-allyl and 111-bound organic ligands. 3) A Pd(0) nucleophile is shown to exhibit dual selectivity with regard to the site of its attack on allylpalladium complexes depending on the nature of their ligands, leading to either redox transmetallation with net inversion of configuration at the allylic sp3- carbon, or p-ally1 Pd-Pd complex formation with retention of stereochemistry. Some novel bonding and reactivity trends in those Pd-Pd bonded complexes which contain p-allyl, p-propargyl and p-diene ligands are also presented.

In a subendothelial space of atherosclerotic arteries, apolipoprotein B-containing lipoproteins are accumulated and oxidized, and the oxidized lipoproteins promote macrophage foam cell formation. Therefore, the analysis of vitamin E, a major antioxidant in lipoproteins, is important for understanding atherosclerotic pathogenesis. A new method for the automated measurement of vitamin-E (γ- and α-tocopherols) in plasma HDL, LDL, and VLDL was established by using anion-exchange-chromatography for separation of lipoproteins, reverse-phase-chromatography for separation of γ- and α-tocopherols in each of lipoproteins, and fluorescent detection. The within-day assay and between-day assay coefficients of variation for lipoprotein tocopherol levels were 4.73-12.84% and 7.00-14.73%, respectively. The γ- and α-tocopherol/cholesterol ratios of VLDL were higher in healthy plasma than in plasma of untreated patients with dyslipidemia, but the ratios of LDL and HDL were not different. This new estimated method can provide the reliable data of lipoprotein vitamin-E and would be useful for the clinical settings.

Complexes of (η5-cyclopentadienyl)(bis(di-p-tolylphosphino)ethane)ruthenium(II) cation with some styrenes containing meta or para substituants were prepared and their NMR spectra examined in detail. Variable-temperature NMR studies on the unsubstituted and para-substituted styrene analogues demonstrated occurrence of a restricted rotation about the C(sp2)—C(sp2) single bond of the styrenes where one of the ortho hydrogens of the styrene phenyl group receives a very large diamagnetic shielding effect by one of the phosphine tolyl groups. Similar studies on the meta-substituted styrene complexes showed existence of two unequally populated conformational isomers arising from the similar restricted rotation where the meta substituent in the dominant isomer was placed further away from the C=C group. The origin of such conformational isomerism was deduced to be the buttressing effect of the meta substituent transmitted via the ortho-hydrogen atom. Key words: buttressing effect, hindered rotation, Ru–styrene complex.

In isolated canine right ventricular muscles, we investigated the differences in antagonisms by beta-blockers against the positive inotropic effects (PIEs) of isoproterenol, a nonselective agonist, and T-0509, a beta1-selective agonist. The selective beta1-blockers atenolol and bisoprolol antagonized the PIE of T-0509 monophasically in Schild analysis, showing pA2 values of 7.05 and 7.63, respectively. On the other hand, both blockers produced biphasic antagonism against the PIE of isoproterenol (ISO); therefore, two pKB values were obtained (7.75 and 4.25 and 7.82 and 5.76, respectively). Nadolol, a nonselective beta-blocker, also antagonized the PIE of T-0509 monophasically (pA2 value 7.58), but antagonized the PIE of ISO biphasically (pKB values 7.42 and 4.39). Because the different mode of antagonism by three beta-blockers between T-0509 and ISO could not be explained by the selectivities of beta-agonists and blockers for beta1- and beta2-adrenoceptors in the heart, two subtypes of beta1-adrenoceptors may exist together in canine ventricular muscles, and atenolol, bisoprolol, and nadolol may act as antagonists for the two subtypes with two different affinities.

Acid-catalyzed rearrangement of 5-cyclopentylidenecyclooctanone derivatives 9a-c was examined to obtain polyspiropolyquinanes 11a-c, considered to have a unique helical structure, through cascade rearrangement pathways consisting of continuous transannular cyclization followed by successive 1,2-alkyl shifts. The substrates were prepared easily by use of the Wittig or McMurry reaction. Reaction of the 5-cyclopentylidenecyclooctanone (9a) with acid gave the expected dispirotriquinane ketone 11a in high yield. The precise mechanism was elucidated by a deuterium-labeling experiment. In the case of the ketone 9b, having another spiroannulated cyclopentane ring attached on 9a, the trispirotetraquiane 11b was not obtained but the bis-propellane-type tetrahydrofuran 25 was produced exclusively. The 5-(5'-cyclopentylidenecyclooctylidene)cyclooctanone (9c) afforded the polycyclic compounds 27-31, depending on the acid used, instead of the desired tetraspiropentaquinane 11c. The structures of the products were determined by NMR spectral data including 2D (13)C INADEQUATE spectra and X-ray crystallographic analyses. The unexpected rearrangement pathways are also discussed.

Some alkyl allyl carbonates and an allylammonium chloride bearing (1-(butyloxy)ethyl)oxy group at the 2-position of the allyl group were synthesized and successfully transformed to oxodimethylenemethane−palladium and −platinum complexes in one step by mixing with a transition metal(0) and triphenylphosphine. On the basis of the confirmation of vinyl ether formation by 1H NMR, the generation of oxodimethylenemethane complexes was rationalized to occur through abstraction of the β-hydrogen on the acetal carbon by an alkoxide ion which was generated from the allyl carbonate upon oxidative addition of the transition metal. The palladium-catalyzed cycloaddition of the acetonylidene group to strained olefins also proceeded successfully by using these alkyl allyl carbonates.

η3-2-Stannylmethylallylpalladium chloride dimer [Pd(η3-CH2C(CH2SnMe3)CH2Cl]2 (1a) reacted with a neutral ligand L to form corresponding cationic complexes [Pd(η3-CH2C(CH2SnMe3)CH2L2]Cl (L = PPh3: 2a, 1 2 bipy: 5 (bipy = 2,2'-bipyridyl)), which were characterized by 1H NMR at low temperature only for 2a and at room temperature for 5. On addition of Bu3SnCl the cationic complex 5 underwent stannyl group exchange equilibrium with [Pd(η3-CH2C(CH2SnBu3)CH2) (bipy)]Cl. Addition of 2 equiv PPh3 and RCHO (R = Ph, CH2=CH) to 1a at room temperature afforded the cycloaddition products, methylenetetrahydrofurans, in good yields. The complex 1a reacted with PhCHO in the presence of bipy and dppe (dppe = 1,2-bis(diphenylphosphino)ethane) to give the aldehyde adduct complexes [Pd(η3-CH2C(CH2CHPh(OSnMe3))CH3L2]Cl (L = 1 2 bipy, 1 2 dppe), which were characterized by 1H NMR. The possible generation and the reactivities of the trimethylenemethane-palladium complex intermediate are discussed in the light of these results.

In canine right ventricular muscle, the influence of ICI 147,798, a slowly dissociable beta 1-adrenoceptor antagonist, on the positive inotropic effect and cyclic AMP production of T-0509, a selective beta 1-agonist, and isoproterenol, a nonselective beta-agonist, were examined to elucidate the properties of the high- and low-affinity states or subtypes of beta 1-adrenoceptor. ICI 147,798 (1 x 10(-8) - 1 x 10(-5) M) produced biphasic concentration-response curves for the positive inotropic effect of T-0509 that were due to its insurmountable antagonism against the lower concentrations of T-0509. The maximum of the biphasic curves were almost the same as Camax. Analysis of hemiequilibrium antagonism by ICI 147,798 against T-0509 showed the dissociation constant (pKB) of ICI 147,798 to be approximately 8. On the other hand, ICI 147,798 produced a parallel rightward shift of the curves of isoproterenol. Schild analysis showed pA2 to be 7.98 +/- 0.04, suggesting competitive antagonism. The concentration-response curve for the increase in cyclic AMP elicited by T-0509 in the presence of 1 x 10(-6) M ICI 147,798 was also biphasic, but slightly depressed as compared with that of control, whereas that elicited by isoproterenol was shifted to the right. The positive inotropy and increase in cyclic AMP produced by T-0509 and isoproterenol in the presence of ICI 147,798 may be mediated by the low-affinity state of beta 1-adrenoceptor, which mechanism may be different from that producing the positive inotropy through the high-affinity state of beta 1-adrenoceptor.

Aim: To examine the effects of supervised aerobic exercise training on serum adiponectin and lipids, including triglyceride (TG)-rich lipoproteins, in moderate dyslipidemic subjects.Methods: Twenty-five dyslipidemic patients [mean body mass index (BMI)=24.6 kg/m2; mean age= 39 years; mean total cholesterol=226 mg/dL; mean TG=149 mg/dL] without metabolic syndrome, diabetes, and hypertension underwent supervised aerobic exercise training (60 min/day, 2 to 3 times/week) at an intensity of 60-80% of age-predicted maximal heart rate for 16 weeks. Lipoprotein cho-lesterol levels were measured by our established anion-exchange HPLC method.Results: Aerobic exercise training significantly decreased BMI, cholesterol levels of LDL- and IDL-, and markedly reduced VLDL-cholesterol at week 8 (-45%) and week 16 (-50%), but changes in TG and HDL-cholesterol were not significant. Adiponectin significantly increased by 51% and HOMA-R was significantly decreased at week 16, although changes in these parameters were not sig-nificant at week 8. There was no significant relationship between changes in adiponectin and in VLDL- or IDL- cholesterol, but changes in adiponectin were inversely but insignificantly associated with changes in BMI (r=-0.343, p=0.095).Conclusions: These results suggest that supervised aerobic exercise training two to three times/week in the presence of body weight loss increases serum adiponectin with an improved lipid profile and insulin sensitivity at week 16 in non-obese moderate dyslipidemic patients, and that VLDL-choles-terol is markedly decreased by supervised aerobic exercise training.

Recent developments in the chemistry of olefin complexes of palladium and platinum are described. Emphasis is placed on the molecular basis on which unique, hitherto unknown stability trends and CC bond coordination geometry in certain complexes can be understood. Examples of these complexes include olefin complexes of PdII and PtII, having the 18-electron configuration or the η3-allyl group as an ancillary ligand, which show stability trends not so strongly affected by the electronic factor of the olefinic substituents. Moreover, the CC axis of the olefin ligand coordinated to the η3-allylmetal moiety tends to lie within the coordination plane. A brief survey on some basic reactivity patterns exhibited by the olefin complexes of palladium and platinum is also given.

We previously established an analysis method for determining the cholesterol levels of five major lipoprotein classes [HDL, LDL, intermediate density lipoprotein (IDL), VLDL, and chylomicrons] in serum by an anion-exchange (AEX)-HPLC method, but lipoprotein(a) [Lp(a)], a well-known risk factor for atherosclerotic diseases, was not determinable. Therefore, we established new AEX-HPLC separation conditions for analyzing the cholesterol levels of six lipoprotein classes, including Lp(a). Serum lipoproteins were separated by HPLC with a diethylaminoethyl-ligand nonporous polymer-based column by elution with a stepwise gradient of the sodium perchlorate concentration. In this improved method, HDL, LDL, IDL, VLDL, chylomicrons, and Lp(a) were each eluted from the column. The cholesterol levels of the eluted lipoproteins were measured enzymatically by a postcolumn reaction. The within-day assay and between-day assay coefficients of variation for the lipoprotein cholesterol levels were in the ranges of 0.29-11.86% and 0.57-11.99%, respectively. The Lp(a) cholesterol levels determined by AEX-HPLC were significantly correlated with the amounts of Lp(a) protein measured by an immunoturbidimetry method available commercially (r = 0.9503, P < 0.0001). Taken together, this AEX-HPLC method may be effectively applied to the analysis of serum lipoproteins with high levels of Lp(a).

An anthropomorphic pelvis phantom was made by the modification of a National Electrical Manufacturers Association (NEMA) phantom, currently the most popular one, and its clinical usefulness was evaluated.The NEMA plus bone phantom was made by placing the pelvic bone model in the NEMA phantom. The NEMA plus bladder phantom was made by placing an imitation of the urinary bladder in the NEMA phantom. The pelvis phantom was also made by placing both the pelvic bone model and the bladder in the NEMA phantom. Four kinds of phantoms were imaged by both 2D and 3D dynamic modes, and for each phantom, prompt coincidence count rates, random ones, true plus scatter ones, and single photon rates were measured and these coincidence count rates were compared with those from the actual clinical data. After image reconstruction, the contrast ratio and image noise were also investigated.For the random coincidence count rate, the data obtained from each phantom showed good correspondence to the clinical data. The prompt coincidence count rates and true plus scatter ones of the clinical data were different from those obtained from NEMA phantom, NEMA plus bone one and NEMA plus bladder one, whereas there was a good correspondence between the data of the pelvis phantom and the clinical data. For the contrast ratio and image noise, there were discrepancies between the data of NEMA phantom and pelvis phantoms.We made an anthropomorphic pelvis phantom by the simple modification of a NEMA phantom. This phantom showed performance similar to that of the actual human pelvis, suggesting clinical usefulness in the evaluation of new acquisition protocols and reconstruction algorithms.

In canine right ventricular muscle, we investigated the mechanism of action of the positive inotropic effects of T-0509 and T-1583, derivatives of denopamine, a new selective beta 1-partial agonist. T-1583 has already been characterized as a selective beta 1 full agonist (pD2 = 7.39). T-0509 also behaved as a full agonist (pD2 = 8.27) and its positive inotropic effect was antagonized competitively by atenolol (pA2 = 7.53) and noncompetitively by carbachol, and potentiated by 3-isobutyl-1-methylxanthine. With increasing concentrations of T-0509 (10(-9) to 10(-7) M) and T-1583 (10(-8) to 10(-6) M), cyclic AMP increased and increases reached plateaus approximately 40% above the baseline levels with approximately 10(-7) M T-0509 and approximately 10(-6) M T-1583, at which their positive inotropic effects reached maxima. However, with further increasing concentrations, cyclic AMP again started to increase and increases amounted to approximately 120% above the baseline levels with 10(-5) M T-0509 and with 10(-4) M T-1583. These results suggest the following: Like denopamine, the selective beta 1 full agonists, T-0509 and T-1583, at lower concentrations produce positive inotropic effects accompanied by only a small increase in cyclic AMP via stimulation of high-affinity beta 1-receptors. In higher concentrations, unlike denopamine, the two full agonists produce large increases in cyclic AMP loosely coupled to positive inotropy via stimulation of low-affinity beta 1-receptors.

ヵチオン識別能をもった二分子膜の構築を目的として,親水基に15-クラウン-5および18-クラゥン-6 エーテル環をもち,ビフェニリレン基を含む一鎖疎水型両親媒性化合物1,2を合成した。18-クラウソ-6誘導体2は,カリウムイオン,特に酢酸カリウム存在下超音波照射によって水中に透明安定に分散した。カルボキシフルオレセィンを蛍光プローブとしてそのトラップ実験を行い,水を内包する粒子の存在を確認した。光散乱光度法で調べた粒径は,疎水基の大きさによってやや異なるものの,ゆ90～98w%以上が120～380Aの範囲にあった。mの分散によって生成したべシクルはイオン性化合物とは異なり,加熱によってベシクル構造は破壊され,内水相が放出された。脂肪酸塩あるいはアルキル硫酸塩を上記2の分散系に混合し,その影響を調べたところ,オレイン酸カリウムはじめカリウムィオンを対イオンとする界面活性物質の塩はi内包水をもった粒子からなる分散系をいちじるしく安定化すること,および小胞体の内包水の量に影響をおよぼすことが明らかとなった。

Improvement in the diagnostic accuracy of lymph node (LN) metastases of colorectal cancer by optimizing the reconstruction parameters was studied, including a phantom study and clinical studies.In the experimental study, the contrast ratio was evaluated using a standard image quality phantom, changing the iteration number of ordered subsets expectation maximization algorithm from 2 to 6. In the clinical study, 89 patients with preoperative colorectal cancer who received 18F-2-deoxy-2-fluoro-D: -glucose positron emission tomography/computed tomography (PET/CT) were studied. Their LN metastases were visually assessed when systematically changing the iteration number, and the optimal iteration number was determined. After the appropriate cut-off value of maximum standardized uptake value was determined, the improvement of the diagnostic accuracy of LN metastases was evaluated for the proximal nodes and the distal ones using the reconstructed images with the optimal iteration number. This was compared with the conventional method that had an iteration number of 2.In the phantom study, it was confirmed that the contrast ratio improved when the iteration number increased. In clinical evaluation, the optimal iteration number was determined to be 5 by visual assessment. When the cut-off value of 1.5 was used, which happened to be the best number, the sensitivity/specificity/accuracy improved from 52%/91%/72% to 77%/89%/83% for the proximal nodes, and from 63%/90%/84% to 91%85%/87% for the distal nodes, respectively.When the iteration number of the reconstruction algorithm was optimized, the sensitivity of LN metastasis improved by more than 20%, and the accuracy exceeded 80%. Optimization of the image reconstruction parameters in the diagnosis of LN metastases using PET/CT is clinically important.

Multiple data evaluation is desirable for data obtained by positron emission tomography (PET), as the data follow the Poisson distribution. Such evaluation, however, tends to be very complicated, since the count- rates change with nuclide decay. To solve this problem, we propose a new data scan protocol in this communication. With this method, the true+scatter coincidence counts were computed during the initial one-minute scanning, which was fixed as the standard. A dynamic scan was then performed with the fixed counts from the high count-rate region. Regions with +/-2.5% of the image noise of the standard image was chosen to provide the data for evaluation. These were found to be the regions of 16.5-25.5 kcps (2D) and 81.1-138.5 kcps. Image quality was found to be affected by noise (2D) and random coincidence. Using this method, multiple data could be obtained by a single experiment, and very reliable image evaluation could be done.

Despite the abundance of “sandwich” complexes, in which two cyclic aromatic hydrocarbon ligands flank a metal center, this motif has not been extended to sheets of multiple metal atoms. We prepared and isolated two such compounds. In the first, three palladium centers form a planar triangular array, capped by chlorides, between two cycloheptatrienyl ligands. In the second, a pentapalladium sheet adopts an edge-sharing triangle-trapezoid skeleton between two naphthacene rings. The compounds were characterized by x-ray crystallography and nuclear magnetic resonance spectroscopy. The nature of bonding in the clusters was analyzed by quantum calculations.

An η1-butadienyl complex [trans-η1-CH2=C(Me)C=CH2Pd(PPh3)2Cl] (1) reacted with [(μ-η2:η2-1,3-butadiene)Pd2(PPh3)(μCl)Cl] (2) to result in displacement of the diene ligand of 2 accompanied by exchange of PPh3 of 1 with Cl anion of 2 producing a butadienyl tripalladium cluster [(μ-CH2=C(Me)C=CH2)Pd(PPh3)Cl2 · Pd2(PPh3)2(μ-Cl)] (3) stabilized by the zwitterionic structure in moderate yield. The X-ray structure analysis of 3 revealed rigid binding of [Pd2(PPh3)2(μ-Cl)]+ and [CH2 =C(Me)C=CH2Pd(PPh3)Cl2]− through the π-bond coordination of the butadienyl group to the dipalladium cation.

Using a continuous superfusion system of dog renal cortical slices, we studied the role of prostacyclin in the control of renin release. Superfusate renin activity and prostacyclin as 6-keto-prostaglandin F1alpha, a stable metabolite of prostacyclin, concentrations were measured by radioimmunoassay. Exogenous prostacyclin (0.1, 1, 10 microM) produced a concentration dependent and significant increase in renin release. The calcium ionophore A23187 (10 microM) produced a significant increase in 6-keto-prostaglandin F1alpha release and a significant decrease in renin release. A23187 (10 microM) hardly produced changes of 6-keto-prostaglandin F1alpha release and renin release in the absence of Ca2+. Pretreatment with indomethacin (10 microM) completely abolished the stimulatory effect of A23187 (10 microM) on 6-keto-prostaglandin F1alpha release. On the other hand, the inhibitory effect of A23187 on renin release in the pretreatment with indomethacin was almost equal to that in the "untreatment" with indomethacin. Moreover, we found that there was no association of 6-keto-prostaglandin F1alpha liberation and renin activity. These results indicate that exogenous prostacyclin promotes renin release, and suggest that renin release is not to be modulated by A23187-induced prostacyclin synthesis in dog renal cortical slices.

Treatment of η 1 -allenyl- or η 1 -propargylpalladium bis(triphenylphosphine) chloride with AgBF 4 or NaBPh 4 afforded cationic η 3 -allenyl/propargylpalladium complexes. The molecular structure and some properties of the η 3 -allenyl/propargylpalladium were revealed.

The first highly substitutionally labile dipalladium (I) complexes are synthesized. The reaction of these reactive dipalladium (I) complexes with unsaturated hydrocarbons such as alkynes, 1, 3-dienes and 1, 3, 5-trienes is surveyed. Unique one-dimensional sandwich compounds made of a palladium chain and polyene ligands are prepared and structurally characterized.