bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Bipolarity’ in bipolar disorder: Distribution of manic and depressive symptoms in a treated population
Authors: Bauer Mark S. , Simon Gregory E. , Ludman Evette , Unützer Jurgen
Published: July 2005

Cross-sectional analysis of 441 individuals with bipolar disorder treated at a US health maintenance organisation investigated the distribution of manic and depressive symptoms in that illness. Clinically significant depressive symptoms occurred in 94.1% of those with (hypo)mania, while70.1% inadepressive episode had clinically significant manic symptoms. DSM-unrecognised depression-plus-hypomania was over twice as prevalent as DSM-recognised mixed episodes. Depressive symptoms were unimodally distributed in (hypo)mania. Depressive and manic symptoms were positively, not inversely correlated, and their co-occurrence was associated with worse quality of life. Implications for the DSM and ICD nosological systems are discussed.
Is clinical service development simply applied evidence-based medicine? A focus group study
Authors: Ruddy Rachel , House Allan
Published: July 2005

Aims and Method

Our aim was to determine the role of evidence and other factors in specialist service development in liaison psychiatry. We held two focus groups with liaison psychiatry practitioners working in different services throughout Europe. A topic schedule focused the discussions, which were taped and transcribed. We used content analysis to identify the role of evidence and other factors that had hindered or facilitated service development.

Results

Our content analysis revealed two factors relating to evidence and 25 other barriers and facilitators of service development, which we grouped into national factors and factors related to local services.

Clinical Implications

Evidence appears to have some impact on service development but many other factors are influential. Clinical service development cannot be understood simply as emerging in response to research evidence.
Partners in care
Authors: Newman Roger
Published: July 2005

The images of other people we see on a daily basis in the media invite us all to compare ourselves with, identify with, or aspire to be like whoever is shown. Mostly this activity is of little significance and hardly touches our lives, but the further we know ourselves to be different from the norm then the more challenging those differences become to us.
What Do We Do Unconsciously? And How?
Authors: Dijksterhuis Ap. , Smith Pamela K.
Published: July 2005

In this reply, we endorse Chartrand's (2005) taxonomy of conscious awareness for different stages of consumer decisions affected by environmental cues. In addition, we attempt to broaden the scope of this taxonomy by discussing its usefulness for consumer decisions in general. We generally support Simonson's (2005) claim that research based on consumers as conscious decision makers is indeed predictive of a wide variety of behavior. However, we also argue that the importance of consciousness should not be overstated. Conscious processes observed in a research laboratory are not representative of conscious processes in real life. The alternative model to describe effects of the environment on behavior by Janiszewski and van Osselaer (2005) may be useful to explain automaticity in goal‐directed behavior, but it poorly describes other automatic behaviors.
The Effects of Sales Message and Suspicion of Ulterior Motives on Salesperson Evaluation
Authors: DeCarlo Thomas E.
Published: July 2005

This research investigates the extent to which a salesperson's presentation and consumer suspicion of ulterior motive affect salesperson evaluations and purchase intentions. Study 1 indicates that a salesperson's presentation plays an essential role in confirming or discontinuing consumer suspicion and that this process has important implications in the formation of salesperson attitudes. Evidence from Study 2 demonstrates that these interaction effects are mediated by persuasion‐motive attributions. The findings also support a direct link between attitude toward the salesperson and purchase intentions. Collectively, these results extend the persuasion literature by demonstrating that suspicion of motive is a dynamic state in which consumers entertain rival hypotheses about the salesperson (e.g., is the salesperson truly motivated to help me, or motivated to make his or her commission?) and that, depending on the degree of suspicion, the same salesperson's tactics will be processed very differently by consumers.
Double Leptin and Melanocortin-4 Receptor Gene Mutations Have an Additive Effect on Fat Mass and Are Associated with Reduced Effects of Leptin on Weight Loss and Food Intake
Authors: Trevaskis James L. , Butler Andrew A.
Published: July 2005

Melanocortin-4 receptors (MC4Rs) are involved in the regulation of food intake, sympathetic nervous activity, and adrenal and thyroid function by leptin. The role of MC4Rs in regulating energy balance by leptin was investigated using double heterozygote or homozygous leptin (Lepob) and Mc4r gene mutant mice. Double heterozygous or homozygous mutants were generated by crossing MC4R knockout (Mc4r−/−) mice, backcrossed onto C57BL/6J, with B6.V-Lepob mice. Energy expenditure was measured using indirect calorimetry. The effect of leptin on food intake, weight loss, insulin, and corticosterone was compared for Lepob/LepobMc4r−/− mice and Lepob/Lepob mice. Double heterozygous and homozygous mutants exhibited an additive effect on fat mass. The 2-fold increase in body weight associated with severe obesity of Lepob/Lepob mice was associated with a significantly higher 24 h total and resting energy expenditure. The effect of obesity on energy expenditure was attenuated by 50% in Lepob/LepobMc4r+/− and Lepob/LepobMc4r−/− mice. Loss of MC4Rs did not affect basal food intake of Lepob/Lepob mice but was associated with partial leptin resistance in terms of food intake and weight loss. Leptin suppression of insulin and corticosterone in Lepob/Lepob mice were not significantly affected by Mc4r genotype. These results suggest a complex interaction between the Lep and Mc4r genes in energy homeostasis and suggest that MC4Rs retain significant anti-obesity function in the obese leptin-deficient state. Increased adiposity with double mutations may involve a reduction in energy expenditure. MC4Rs might have a modest role in the regulation of energy balance by exogenously administered leptin, primarily effecting food intake.
Stimulation of Resorption in Cultured Mouse Calvarial Bones by Thiazolidinediones
Authors: Schwab A. M. , Granholm S. , Persson E. , Wilkes B. , Lerner U. H. , Conaway H. H.
Published: July 2005

Dosage-dependent release of 45Ca was observed from prelabeled mouse calvarial bones after treatment with two thiazolidinediones, troglitazone and ciglitazone. Release of 45Ca by ciglitazone was decreased by the osteoclast inhibitors acetazolamide, calcitonin, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate, and IL-4, but not affected by the peroxisome proliferator-activated receptor γ antagonist, GW 9662, the mitotic inhibitor, hydroxyurea, or indomethacin. Enhanced expression of receptor activator of nuclear factor-κB ligand (RANKL) mRNA and protein and decreased osteoprotegerin (OPG) mRNA and protein were noted after ciglitazone treatment of calvariae. Ciglitazone and RANKL each caused increased mRNA expression of osteoclast markers: calcitonin receptor, tartrate-resistant acid phosphatase, cathepsin K, matrix metalloproteinase-9, integrin β3, and nuclear factor of activated T cells 2. OPG inhibited mRNA expression of RANKL stimulated by ciglitazone, mRNA expression of osteoclast markers stimulated by ciglitazone and RANKL, and 45Ca release stimulated by troglitazone and ciglitazone. Increased expression of IL-1α mRNA by ciglitazone was not linked to resorption stimulated by the thiazolidinedione. Ciglitazone did not increase adipogenic gene expression but enhanced osteocalcin mRNA in calvariae. In addition to exhibiting sensitivity to OPG, data indicate that stimulation of osteoclast differentiation and activity by thiazolidinediones may occur by a nonperoxisome proliferator-activated receptor γ-dependent pathway that does not require cell proliferation, prostaglandins, or IL-1α but is characterized by an increased RANKL to OPG ratio.
Rapid Glucocorticoid-Mediated Endocannabinoid Release and Opposing Regulation of Glutamate and γ-Aminobutyric Acid Inputs to Hypothalamic Magnocellular Neurons
Authors: Di Shi , Malcher-Lopes Renato , Marcheselli Victor L. , Bazan Nicolas G. , Tasker Jeffrey G.
Published: July 2005

Glucocorticoids secreted in response to stress activation of the hypothalamic-pituitary-adrenal axis feed back onto the brain to rapidly suppress neuroendocrine activation, including oxytocin and vasopressin secretion. Here we show using whole-cell patch clamp recordings that glucocorticoids elicit a rapid, opposing action on synaptic glutamate and γ-aminobutyric acid (GABA) release onto magnocellular neurons of the hypothalamic supraoptic nucleus and paraventricular nucleus, suppressing glutamate release and facilitating GABA release by activating a putative membrane receptor. The glucocorticoid effect on both glutamate and GABA release was blocked by inhibiting postsynaptic G protein activity, suggesting a dependence on postsynaptic G protein signaling and the involvement of a retrograde messenger. Biochemical analysis of hypothalamic slices treated with dexamethasone revealed a glucocorticoid-induced rapid increase in the levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The glucocorticoid suppression of glutamate release was blocked by the type I cannabinoid receptor cannabinoid receptor antagonist, AM251, and was mimicked and occluded by AEA and 2-AG, suggesting it was mediated by retrograde endocannabinoid release. The glucocorticoid facilitation of GABA release was also blocked by AM251 but was not mimicked by AEA, 2-AG, or a synthetic cannabinoid, WIN 55,212–2, nor was it blocked by vanilloid or ionotropic glutamate receptor antagonists, suggesting that it was mediated by a retrograde messenger acting at an AM251-sensitive, noncannabinoid/nonvanilloid receptor at presynaptic GABA terminals. The combined, opposing actions of glucocorticoids mediate a rapid inhibition of the magnocellular neuroendocrine cells, which in turn should mediate rapid feedback inhibition of the secretion of oxytocin and vasopressin by glucocorticoids during stress activation of the hypothalamic-pituitary-adrenal axis.
Emx2 Regulates Mammalian Reproduction by Altering Endometrial Cell Proliferation
Authors: Taylor Hugh S. , Fei Xiaolan
Published: July 2005

The molecular mechanisms that underlie embryo implantation are poorly understood. Under the control of sex steroids, uterine endometrium undergoes tremendous, yet tightly controlled, proliferation in each estrous cycle to facilitate implantation; disorders of endometrial proliferation underlie several uterine diseases. We have previously identified the Emx2 gene as a transcriptional target of HOXA10 regulation in the reproductive tract. Here we report the function of Emx2 in murine implantation and regulation of endometrial proliferation. We transfected mice on d 2 post coitus with pcDNA3.1/Emx2, Emx2 antisense, or respective controls consisting of empty pcDNA3.1 or a random order oligonucleotide by intrauterine lipofection. Increased expression of Emx2 reduced average implantation rate by approximately 40% (P = 0.00006) resulting in an average number of implanted embryos per litter of 13.7 in the control group to 8.2 in the pcDNA3.1/Emx2-treated group. Neither treatment altered the number of mice attaining pregnancy with at least one embryo. Decreased Emx2 expression did not alter litter size. Neither treatment affected the birth weight of the pups. To elucidate potential mechanisms through which Emx2-regulated reproduction, markers of endometrial differentiation, proliferation, and apoptosis were assessed. Increased Emx2 expression significantly decreased endometrial cell proliferating cell nuclear antigen expression and 5′-bromo-2′ deoxyuridine incorporation. Markers of stromal cell differentiation (IGF binding protein-1, prolactin), epithelial differentiation (calcitonin), and apoptosis (activated caspase3) were unchanged. In human endometrial epithelial cells in vitro, Emx2 reduced cell number indicating diminished proliferation. Emx2 controls mammalian reproduction by adjusting endometrial cell proliferation without effecting differentiation. Regulated uterine Emx2 expression is necessary during reproduction for maximal implantation and litter size.
Development of an Antiferromagnetic Organic Superconductor κ-(BETS)2FeBr4
Authors: Fujiwara Hideki , Kobayashi Hayao
Published: July 2005

The first antiferromagnetic organic superconductor, κ-(BETS)2FeBr4 [BETS = bis(ethylenedithio)tetraselenafulvalene], was developed in the search for novel magnetic molecular conductors. This salt shows successive antiferromagnetic and superconducting transitions at TN = 2.5 K and Tc = 1.1 K, respectively, at ambient pressure. Specific heat measurements and anisotropic behavior of intraplanar conducting properties under applied magnetic fields prove the coexistence of the antiferromagnetic ordering and superconductivity below Tc. The combination of metamagnetism of the magnetic layer and superconductivity of the conduction layer, which makes this salt a dual-functional system, yields two characteristic magnetic field-induced superconducting states around 1.6 and 12.5 T in terms of the Jaccarino–Peter compensation effect. Systematic studies on both the chemical pressure effect by a halogen exchange in the alloy system κ-(BETS)2FeBrxCl4−x and the physical pressure effect by an application of real pressures in κ-(BETS)2FeBr4 were performed to discuss the π–d interaction in the κ-(BETS)2FeBr4 system.
Bioluminescence in the Limpet-Like Snail, Latia neritoides
Authors: Ohmiya Yoshihiro , Kojima Satoshi , Nakamura Mitsuhiro , Niwa Haruki
Published: July 2005

Latia neritoides is a small limpet-like snail that produces a bright green bioluminescence; it is found only in New Zealand streams. The light-emitting system is unique. Although Latia bioluminescence has been studied since 1880, its mechanism is unclear. Shimomura and Johnson clarified the elements of the mechanism, including the structures of luciferin and luciferase, in 1968. However, neither the emitter nor the mechanism of the excited state of luciferin has been determined. We studied molecular mechanisms to clarify the characteristics of luciferin and luciferase and to produce a new application for this system.
Cycloaddition of “N-Acyliminium Ion Pools” with Carbon–Carbon Multiple Bonds
Authors: Suga Seiji , Tsutsui Yamato , Nagaki Aiichiro , Yoshida Jun-ichi
Published: July 2005

N-Acyliminium ion pools, which are generated from α-silyl carbamates, were found to react with a variety of alkenes and alkynes to give the corresponding cycloadducts. The reaction with styrene derivatives gave rise to the formation of a significant amount of polymeric products. The use of micromixing, however, resulted in a significant increase in the yield of the cycloadduct at the expense of the polymer. Mechanistic studies indicated that a concerted mechanism seems to be most likely for alkyl-substituted alkenes, whereas a stepwise mechanism seems to be reasonable for aryl-substituted alkenes.
Molecular Symmetry Group as Applied to the Spectroscopy of Molecules with Methyl Groups: Toluene, Nitromethane, and 5-Methyltropolone’s
Authors: Kanamaru Nobuaki
Published: July 2005

A theory of the molecular symmetry group (MSG) is presented to describe the spectroscopy of molecules that consist of methyl (top) and planar (frame) groups and belong to the G12 MSG. This was done in a form of Fourier-series expansion on the torsional angle of the methyl group concerning its two kinds of coupling terms, by choosing three kinds of systems in the title: (1) A morphing technique to describe the vibronic coupling is applied to interpret the torsionally induced S1 ← S0 absorption spectra of toluene (as partially described in a recent Letter). (2) The torsion–vibration coupling term in the top (through its interaction with the frame) was confirmed to split the degenerate e′ levels of either vibrational or torsional modes into either a1″ + a2″ levels/modes or a1′ + a2′ levels, respectively. The latter was made with the interpretation of either broad IR absorption spectra of nitromethane or peculiar low-frequency bands in the electronic spectra of 5-methyltropolone, respectively.
Reaction of (COCl)2 with AgN3: Evidence for the Formation of Oxalyl Diazide O2C2(N3)2
Authors: Fengyi Liu , Xiaoqing Zeng , Qiao Sun , Lingpeng Meng , Shijun Zheng , Xicheng Ai , Jianping Zhang , Maofa Ge , Dianxun Wang
Published: July 2005

Oxalyl diazide O2C2(N3)2 has been generated in the heterogeneous reaction of (COCl)2 vapor with AgN3 at room temperature. Evidence for the formation of O2C2(N3)2 is based on on-line photoelectron spectroscopy (PES) characterization combined with the density functional B3LYP and outer valence Green’s function (OVGF) calculations. The good agreement between the experimental spectra and theoretical calculation shows that O2C2(N3)2 has adiabatic ionization energy of 10.11 eV. Our results also suggest that O2C2(N3)2 has high conformational flexibilities and that the planar conformers are energy-favorable in gas phase.
On Infrared Intensities of Spinel, MgAl2O4
Authors: Kanesaka Isao , Hayashi Yuichi , Morioka Yoshiyuki
Published: July 2005

In spinel (MgAl2O4), the strongest infrared band at 485 cm−1 shows less LO–TO splitting than the medium band at 670 cm−1. This unexpected relationship is explained in terms of the vibrational coupling of these TO modes. A new manner for evaluating the LO mode is proposed.
Growth of Hexagonal Bipyramidal Ruby Crystals by the Evaporation of a Li2O–MoO3 Flux
Authors: Teshima Katsuya , Kondo Hitoshi , Oishi Shuji
Published: July 2005

The growth of hexagonal bipyramidal ruby crystals by the flux evaporation method in the Li2O–MoO3 flux system has been reported. Ruby crystals were grown by heating a mixture of a solute (Al2O3 + 0.5 wt % Cr2O3) and a flux (Li2O–MoO3) at 1050, 1100, or 1200 °C, followed by holding the solution at these temperatures for 5 h. The crystal size was dependent on the evaporation loss of the flux. The evaporation loss of the flux gradually decreased with increasing amount of Li2O added to MoO3, and increased with the holding temperature. The obtained ruby crystals had lengths of up to 2.6 mm and widths of up to 2.1 mm, and had a transparent-red color. Their form was a bipyramid, bounded by well-developed faces. The most suitable flux composition for high-quality and large ruby crystal growth was found to be 2 mol % Li2O–98 mol % MoO3.
Observation of a Large Current on the Cyclic Voltammetry of Acylaminoferrocenes in the Solid State: An Efficient Electron-Transfer Pathway through Continuous NH···O=C Hydrogen-Bond Chains and π-Conjugation
Authors: Okamura Taka-aki , Sakauye Keiko , Doi Mototsugu , Yamamoto Hitoshi , Ueyama Norikazu , Nakamura Akira
Published: July 2005

A series of crystal structures of acylaminoferrocenes, [(C5H5)Fe(C5H4NHCOR)] (R = CH3 (1), CH2CH3 (2), t-Bu (3), and CF3 (4)) revealed an unusually delicate dependence of the alkyl substituent structure on electron transfer through NH···O=C bonding and π-conjugation. The presence of strong intermolecular NH···O=C hydrogen bonds in the crystal was established by X-ray, IR, and CRAMPS. Compounds 1 and 2 are without steric or electrostatic hindrance, and both exhibit continuous and strong hydrogen-bond chains, or an effective π-electrons system. However, the hydrogen-bond chains in 3 and 4 are weak, or broken, by the bulkiness of t-Bu or the electrostatic repulsion of CF3. Solid-state cyclic voltammograms of 1–4 have revealed the electrochemical processes, which are critically dependent on the array and the strength of the hydrogen bonds. Although both 3 and 4 show typical reversible cyclic voltammograms, 1 and 2 exhibit irreversible redox behaviors and remarkably large current values, which indicate the presence of an effective electron transfer through the continuous hydrogen-bond chains.
Infinite Chain Structure and Steep Spin Crossover of a FeIII Complex with a N3O2 Pentadentate Schiff-Base Ligand and 4-Aminopyridine
Authors: Tanimura Kyoichi , Kitashima Ryoko , Bréfuel Nicolas , Nakamura Masaaki , Matsumoto Naohide , Shova Sergiu , Tuchagues Jean-Pierre
Published: July 2005

A spin crossover (SC) FeIII complex, [FeIII(4-NH2py)L]BPh4, was synthesized and characterized, where 4-NH2py = 4-aminopyridine, H2L = pentadentate N3O2 Schiff-base ligand of the 2:1 condensation product of 3-methoxysalicylaldehyde and bis(3-aminopropyl)methylamine, and BPh4− = tetraphenylborate. Cryomagnetic susceptibility measurements revealed a steep spin transition between FeIII low-spin (S = 1/2) and high-spin (S = 5/2) states at T1/2 = 120 K, but showed no hysteresis. Crystal-structural analyses were performed at 293 and 90 K in order to investigate the origin of the steep spin crossover, and to determine the structures of the high-spin and low-spin states. The crystal structure consisted of a one-dimensional chain constructed by hydrogen bonds between the amino group of 4-NH2py of a molecule and the methoxy group of the adjacent molecule.
A Solvothermal Synthesis and the Structure of (NH4)2Ag6Sn3S10
Authors: BaiYin Menghe , Ye Ling , An Yonglin , Liu Xin , Jia Cuiying , Ning Guiling
Published: July 2005

A novel framework, (NH4)2Ag6Sn3S10, was synthesized solvothermally and characterized by single-crystal X-ray diffraction. The framework comprises silver-rich cationic layers, [Ag6SnS4]2+, pillared by [SnS3]2− zigzag chains formed by vertex-sharing SnS4 tetrahedra; NH4+ ions are located in 1D channels.
Zn(II) Complexes with Aliphatic Thiolates. (Et4N)[Zn(SAd)3] and (Et4N)2[{Zn(ScHex)2}2(μ-ScHex)2]
Authors: Matsunaga Yuki , Fujisawa Kiyoshi , Ibi Naoko , Amir Nagina , Miyashita Yoshitaro , Okamoto Ken-ichi
Published: July 2005

New homoleptic aliphatic thiolato complexes with Zn(II), (Et4N)[Zn(SAd)3] (1) (HSAd = 1-adamantanethiol), and (Et4N)2[{Zn(ScHex)2}2(μ-ScHex)2] (2) (HScHex = 1-cyclohexanethiol), have a novel three-coordinate geometry for monomeric 1 and a tetrahedral geometry for dimeric 2, respectively. The complexes have been fully characterized by far-IR, Raman, and UV–vis absorption spectroscopy.
Dinuclear Pt(II) and Pd(I) Complexes with Bridging PPh2 Ligands from the Reaction of PPh2H with Zero-Valent Complexes of These Metals
Authors: Tanabe Makoto , Itazaki Masumi , Kitami Osamu , Nishihara Yasushi , Osakada Kohtaro
Published: July 2005

Reactions of PPh2H with [M(PCy3)2] (M = Pt, Pd) produce the dinuclear complexes with bridging PPh2 ligands of these metals, [{Pt(H)(PCy3)}2(μ-PPh2)2] and [{Pd(PCy3)}2(μ-PPh2)2], respectively.
Metal Ion-Induced Hetero-Block α-Helical Coiled Coil
Authors: Kashiwada Ayumi , Nakamura Yohei , Matsuda Kiyomi
Published: July 2005

To construct polypeptides that undergo a hetero-block α-helical coiled coil structure change due to metal ion-induced self-assembly formation, we designed two kinds of 18-residue polypeptides, Pep3 and Pep4, each with a metal binding site. Pep3 and Pep4 were designed based on the sequence of the isoleucine zipper polypeptide forming the triple-stranded α-helical coiled coils. While Pep3 and Pep4 are too short to form a parallel triple stranded α-helical coiled coil individually, they form the hetero-block α-helical coiled coil structure, (Pep3)3–Ni2+–(Pep4)3 in the presence of the Ni2+ ions. Circular dichroism spectroscopy and size-exclusion gel-filtration chromatography analyses revealed the formation of the (Pep3)3–Mn+–(Pep4)3 hetero-block α-helical coiled coil complex.
Chemical and Genetic Study of Ligularia tongolensis, Ligularia cymbulifera, and Ligularia atroviolacea in the Hengduan Mountains of China
Authors: Hanai Ryo , Gong Xun , Tori Motoo , Kondo Satomi , Otose Kanako , Okamoto Yasuko , Nishihama Tadaaki , Murota Akihiko , Shen Yuemao , Wu Sugong , Kuroda Chiaki
Published: July 2005

Three Ligularia species (L. tongolensis, L. cymbulifera, and L. atroviolacea) were examined with respect to the chemical composition and nucleotide sequence. Furanoeremophilanes were found to be produced in the root of all samples of the three species collected in northwest Yunnan and southwest Sichuan. Eight furanoeremophilanes were identified, two of which were new. Most of the identified furanoeremophilanes were oxygenated at 3, 6, and 15-positions. The nucleotide sequence of the atpB-rbcL intergenic region was found to be essentially the same in the three species. These similarities imply that the three Ligularia species, all belonging to the section Corymbosae, are close to one another. The intra-specific diversity in the two widely distributed species in the Hengduan Mountains area, L. tongolensis and L. cymbulifera, were in contrast. Four out of 19 L. tongolensis samples contained a strongly Ehrlich-positive compound besides a number of positive compounds, and five variants of the atpB-rbcL sequence were found in these samples. In contrast, no variation was observed in 13 L. cymbulifera samples with respect to the furanoeremophilane composition or the atpB-rbcL sequence. The lack of diversity in L. cymbulifera probably resulted from the uniformity of its habitat.
Highly Stereoselective Samarium(II) Iodide-Mediated Aldol Reactions of Acylaziridines with Aldehydes
Authors: Ogawa Yasuyuki , Kuroda Kiichi , Mukaiyama Teruaki
Published: July 2005

The samarium(II) iodide-mediated stereoselective aldol reactions of acylaziridines with aldehydes are described. β-Amino–β′-hydroxy ketones were synthesized in high yields by the aldol reaction of aldehydes with samarium enolates generated by aziridine-fragmentation of aziridinyl ketones with two moles of samarium(II) iodide. By the choice of an appropriate nitrogen protecting group, depending on the substituent at C-3 position of aziridinyl ketone, anti,anti-β-amino–β′-hydroxy ketones were diastereoselectively obtained among the four possible diastereomers. Further, enantiomerically pure anti,anti-β-amino–β′-hydroxy ketones were successfully obtained by this aldol reaction when chiral aziridinyl ketones were used. In addition, δ-amino–β′-hydroxy–β,γ-unsaturated esters were also synthesized in high yields by the aldol reaction of aldehydes with samarium enolates generated by aziridine-fragmentation and olefin-migration of γ,δ-aziridinyl–α,β-unsaturated esters using two moles of samarium(II) iodide. This aldol reaction proceeded with complete α-regioselectivity and formed (E)-olefin selectively. By introducing chiral oxazolidin-2-one auxiliary to γ,δ-aziridinyl–α,β-unsaturated carbonyl system, this reaction was extended successfully to the asymmetric reaction and enantiomerically pure syn-δ-amino–β′-hydroxy-β,γ-unsaturated esters were obtained in high yields.
Conformation Dependence of Photophysical Properties of σ–π Conjugation as Demonstrated by cis- and trans-1,2-Diaryl-1,2-disilacyclohexane Cyclic Systems
Authors: Tsuji Hayato , Shibano Yuki , Takahashi Tohru , Kumada Makoto , Tamao Kohei
Published: July 2005

Several configurationally constrained cis- and trans-1,2-diaryl-1,2-dimethyl-1,2-disilacyclohexanes (3a–e) have been synthesized in order to measure their photophysical properties, such as UV absorption, magnetic circular dichroism (MCD), and photoluminescence. As has been well established, the UV absorption maximum (1La band) occurs at 230–270 nm, due to the effective σ–π conjugation between the aryl groups and the disilane moiety. The absorption maximum wavelength of the trans isomer is slightly longer than that of the cis isomer for all the diaryldisilanes employed in the present study. Although the MCD spectra of the cis- and trans-1,2-diphenyl-1,2-dimethyl-1,2-disilacyclohexanes (3a) show only a slight configuration dependence, this method is helpful to detect a weak 1Lb band. The disilanes 3a and 5a show a charge-transfer (CT) emission band. The quantum yields are dependent on the disilane configuration and the solvent polarity; the order of the quantum yield is cis-3a < 5a < trans-3a in 3-methylpentane, while the order is 5a < cis-3a < trans-3a in acetonitrile. These results demonstrate that the conformation constraint is effective for controlling the photophysical properties of the diaryldisilanes.
Isolation of Two 13-epi-Neoverrucosane-Type Diterpenoids from a Marine Sponge Axinyssa tethyoides
Authors: Shimogawa Hiroki , Teruya Toshiaki , Suenaga Kiyotake , Kigoshi Hideo
Published: July 2005

New 13-epi-neoverrucosane-type diterpenes 1 and 2 were isolated from the marine sponge Axinyssa tethyoides. Their structures were elucidated by 2D-NMR spectroscopy, the modified Mosher’s method, and fluorescent X-ray analysis. 1 and 2 are the first 13-epi-neoverrucosane-type diterpenes that possess a sulfate group.
Multivariate Analysis and Experimental Design in the Screening of Combinatorial Libraries of Molecular Imprinted Polymers
Authors: Navarro Villoslada Fernando , Takeuchi Toshifumi
Published: July 2005

The combination of an experimental design/multivariate analysis method and a high-throughput technique was developed in the screening and evaluation of molecular imprinted polymers (MIPs). Combinatorial libraries of MIPs were prepared automatically at a reduced scale and screened for high affinity with regard to six experimental factors with a large impact in the MIP synthesis: the amounts of the functional monomer, cross-linker and template; the volume of the porogen, the amount of the initiator and the types of initiation. With the objective of optimizing a polymer imprinted with the non-steroidal anti-inflammatory drug piroxicam, different polymer libraries were prepared by varying the six factors according to a two-level fractional factorial design of resolution VI. This optimization resulted in polymers showing high affinity as a result, mainly, of reduced binding to the non-imprinted polymers. The type of cross-linker showed a strong influence on the specific binding of the template when assessed by equilibrium rebinding experiments. The cross-linking monomer divinylbenzene gave rise to an enhancement in the binding capacity of the MIP that may be attributed to its similar structure with the functional monomer considered (4-vinylpyridine). The binding capacity of the MIP and blank polymers was related to the six experimental factors using a partial least squares regression (PLS) method. The regression models of the polymer libraries showed the same trend in the MIP and blank polymers, suggesting a higher specific binding capacity when the polymerization was photoinitiated at low temperature; the amounts of the functional monomer and the cross-linker were similar. The proposed procedure is time and cost effective and can be used as a general tool for preparing MIPs for different analytes. The proposed method provides new insight into the influence and interaction of the main factors that affect the MIP performance that could facilitate improvements in the MIP process design in the future.
Specific Acceleration of the Hydrogenation of Methyl Acetoacetate on Enantio-Differentiating Sites of a Tartaric Acid-Modified Nickel Catalyst by the Addition of Acetic Acid to the Reaction Media
Authors: Osawa Tsutomu , Ando Masashi , Harada Tadao , Takayasu Osamu
Published: July 2005

The hydrogenation of methyl acetoacetate on enantio-differentiating sites of a tartaric acid-modified nickel catalyst was specifically accelerated by the addition of acetic acid to the reaction media to increase the enantio-differentiating ability of the catalyst.
Cardiomyocytes of Chronically Ischemic Pig Hearts Express the MDR-1 Gene-encoded P-glycoprotein
Authors: Lazarowski Alberto J. , Rivello Hernán J. García , Janavel Gustavo L. Vera , Cuniberti Luis A. , Meckert Patricia M. Cabeza , Yannarelli Gustavo G. , Mele Aníbal , Crottogini Alberto J. , Laguens Rubén P.
Published: July 2005

The multidrug-resistant (MDR)-1 gene-encoded P-glycoprotein (Pgp-170) is not normally present in the cardiomyocyte. Given that in other tissues Pgp-170 is not found under normoxic conditions but is expressed during hypoxia, we searched for Pgp-170 in chronically ischemic porcine cardiomyocytes. Pgp-170 was detected and localized via immunohistochemistry in ischemic and nonischemic cardiomyocytes of eight adult pigs 8 weeks after placement of an Ameroid constrictor at the origin of the left circumflex artery (Cx). Regional myocardial ischemia in the Cx bed was documented with nuclear perfusion scans. Pgp-170 mass was quantified using Western blot analysis. In all pigs, Pgp-170 was consistently present in the sarcolemma and T invaginations of the cardiomyocytes of the ischemic zone. Pgp-170 expression decreased toward the border of the ischemic zone and was negative in nonischemic regions as well as in the myocardium of sham-operated animals. Western blot analysis yielded significantly higher Pgp-170 mass in ischemic than in nonischemic areas. We conclude that Pgp-170 is consistently expressed in the cardiomyocytes of chronically ischemic porcine myocardium. Its role in the ischemic heart as well as in conditions such as myocardial hibernation, stunning, and preconditioning may have potentially relevant clinical implications and merits further investigation.
Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study
Authors: Isobe Takeshi , Saitoh Shigeyuki , Takagi Satoru , Takeuchi Hiroshi , Chiba Yu , Katoh Nobuo , Shimamoto Kazuaki
Published: July 2005

Design: The aim of this study was to determine the association between aging and adiponectin level from the aspect of the influence of renal function and sex hormones in humans.

Methods: Serum adiponectin and blood urea nitrogen (BUN) levels were measured in 964 subjects (372 males) aged 60.3±12.5 years. Testosterone and free testosterone levels were measured in 123 males, and estrone and estradiol levels were measured in 114 females. The subjects were divided into two age groups; 65 years of age or older (Age ≥65 group) and less than 65 years of age (Age <65 group).

Results: Adiponectin level increased linearly with aging in males, whereas it increased dramatically in females until their 50s. The patterns of changes in adiponectin were similar to those in BUN. In multiple- regression analysis using adiponectin as a dependent variable BUN was selected as a significant independent variable in all subjects and in subjects in the Age ≥65 group, whereas bioactive sex hormones were not selected.

Conclusions: A decrease in adiponectin clearance in the kidney may be the cause of high levels of adiponectin in the elderly. Adiponectin level seems to be influenced more strongly by BUN than by sex hormones and to be increased by a decline in renal function with aging.
Hip bone mineral density, bone turnover and risk of fracture in patients on long-term suppressive L-thyroxine therapy for differentiated thyroid carcinoma
Authors: Heijckmann A Caroline , Huijberts Maya S P , Geusens Piet , de Vries Jolanda , Menheere Paul P C A , Wolffenbuttel Bruce H R
Published: July 2005

Objective: Untreated hyperthyroidism and treatment with high doses of thyroid hormone are associated with osteoporosis. However, their effect on bone turnover, their contribution to bone mineral density (BMD) in the context of other clinical risk factors for osteoporosis and the prevalence of vertebral fractures is not well documented.

Design: Cross-sectional study.

Methods: We studied 59 patients receiving L-thyroxine suppressive therapy for differentiated thyroid carcinoma (DTC). BMD of the hip was measured by dual X-ray absorptiometry (DXA) and lateral DXA pictures of the lumbar and thoracic vertebrae were performed. Bone resorption was measured by C-telopeptides of type I collagen (ICTP) and bone formation by procollagen type I N-propeptide (PINP). Clinical risk factors for osteoporosis were evaluated using a questionnaire.

Results: Z-scores of BMD were similar as the NHANES (National Health and Nutrition Examination Survey) III reference group in women and men, also after long-term (>10 years) suppression therapy. Patients in the lowest and highest quartile of BMD showed significant differences in the presence of clinical risk factors. ICTP levels were significantly higher than in age-matched controls, PINP levels were not different. We found four patients with a prevalent vertebral fracture.

Conclusions: We conclude that patients with well-differentiated thyroid carcinoma are not at increased risk of developing low bone mass nor have a higher prevalence of vertebral fracture at least when treated with relatively low doses of l-thyroxine.
Limited predictive value of an acute test with subcutaneous octreotide for long-term IGF-I normalization with Sandostatin LAR in acromegaly
Authors: de Herder Wouter W , Taal H Rob , Uitterlinden Piet , Feelders Richard A , Janssen Joop A M J L , van der Lely Aart-Jan
Published: July 2005

Objectives: To study whether the growth hormone (GH) response after the subcutaneous administration 50 μg of octreotide (acute octreotide test) has any predictive value for long-term IGF-I normalization with Sandostatin LAR.

Design: Twenty four therapy-naive patients with active acromegaly were studied.

Results: >75% GH decrease in the acute octreotide test predicted long-term IGF-I normalization with Sandostatin LAR in 8/11 (73%) of patients. 3/13 (23%) patients with <75% GH decrease in the acute octreotide test were long-term biochemically controlled with Sandostatin LAR. Using the >75% GH reduction criterion, the sensitivity and specificity of this test for predicting long-term normalization of serum IGF-I with Sandostatin LAR treatment were 73% and 77%, respectively (positive and negative predictive values: 73% and 77%, respectively). 6/8 (75%) patients with GH suppression to levels <1.1 μg/l and 9/16 (56%) patients with GH suppression to levels <2 μg/l in the acute octreotide test showed normalization of serum IGF-I with long-term Sandostatin LAR treatment. The sensitivity and specificity of GH suppression <1.1 μg/l for predicting of the long-term normalization of serum IGF-I with Sandostatin LAR therapy were 55% and 85%, respectively (positive and negative predictive values: 75% and 69%, respectively). The sensitivity and specificity of GH suppression <2 μg/l for predicting of the long-term normalization of serum IGF-I with Sandostatin LAR therapy were 82% and 46%, respectively (positive and negative predictive values: 56% and 75%, respectively).

Conclusion: The acute octreotide is not recommended for clinical decision making with regard to long-term treatment using the long-acting somatostatin analog Sandostatin LAR in acromegaly.
Differential gene expression in pituitary adenomas by oligonucleotide array analysis
Authors: Morris Damian G , Muşat Mädälina , Czirják Sándor , Hanzély Zoltán , Lillington Debra M , Korbonits Márta , Grossman Ashley B
Published: July 2005

Objectives: Microarray technology allows for the expression profile of many thousands of genes to be quantified at the same time, and has resulted in novel discoveries about the tumour biology of a number of cancers. We sought to do this in pituitary adenomas, the most common intracranial neoplasm.

Methods: Affymetrix GeneChip HG-U133A oligonucleotide arrays covering 14 500 well-characterised genes from the human genome were used to study pooled RNA for each of the four major pituitary adenoma subtypes. Individual gene-expression levels in the tumours were compared relative to the expression profile in normal pooled pituitary RNA. Three differentially expressed genes with potential importance in tumourigenesis were chosen for validation by real-time quantitative PCR on the original tumours and on an additional 26 adenomas.

Results: Bioinformatic analysis showed that 3906 genes and 351 expressed sequence tags were differentially expressed among all pituitary tumour subtypes. Lysosomal-associated protein transmembrane- 4-β (LAPTM4B), a novel gene upregulated in hepatocellular carcinoma, was significantly over-expressed in adrenocorticotrophin (ACTH)-secreting adenomas and non-functioning pituitary adenomas (NFPAs). Bcl-2-associated athanogene (BAG1), an anti-apoptotic protein found at high levels in a number of human cancers, was significantly over-expressed in growth hormone-secreting and prolactin-secreting adenomas and NFPAs. The cyclin-dependent kinase inhibitor p18, in which murine gene deletion has been shown to produce pituitary ACTH cell hyperplasia and adenomas, was significantly under-expressed in ACTH-secreting adenomas.

Conclusions: Expression array analysis of pituitary adenomas using the Affymetrix GeneChip HG-U133A arrays appears to be a valid method of identifying genes that may be important in tumour pathogenesis.
Platelet-activating factor and human thyroid cancer
Authors: Denizot Yves , Chianéa Thierry , Labrousse François , Truffinet Véronique , Delage Manuela , Mathonnet Muriel
Published: July 2005

Objective: Platelet-activating factor (PAF) is a pro-inflammatory and angiogenic lipid mediator involved in several types of cancer in humans. The levels of PAF, lyso-PAF (the PAF precursor), phospholipase A2activity (PLA2, the enzymatic activity implicated in lyso-PAF formation) and acetylhydrolase activity (AHA, the PAF-degrading enzyme) were investigated in various diseased thyroid tissues.

Subjects: Control and diseased tissue of patients with a hyperplastic goitre (n= 14), a benign adenoma (n= 12) and a papillary thyroid carcinoma (n= 15) were investigated.

Results: PAF receptor transcripts were found in the human thyroid tissue. PAF, lyso-PAF, PLA2and AHA were present in control thyroid tissues, their levels being significantly correlated with each other, suggesting tiny regulations of the PAF metabolic pathways inside the thyroid gland. PAF, lyso-PAF, PLA2and AHA levels remained unchanged in diseased tissues of patients with a hyperplastic goitre, a benign adenoma and a papillary thyroid carcinoma. No difference was found between PAF, lyso-PAF, PLA2and AHA levels with respect to the TNM tumour status and the histological sub-type of papillary thyroid carcinoma. No correlation was found between tissue PAF levels and those of vascular endothelial growth factor and basic fibroblast growth factor, two angiogenic growth factors involved in thyroid cancer and that mediate their effect through PAF release in breast and colorectal cancer.

Conclusion: PAF, PAF receptor transcripts and the enzymatic activities implicated in PAF production and degradation are present in the thyroid gland. While the physiological role of PAF is presently unknown in thyroid physiology, this study highlights no evidence for a potentially important role of PAF during human thyroid cancer, a result that markedly differs from breast and colorectal ones.
History and perspectives of pituitary folliculo-stellate cell research
Authors: Allaerts Wilfried , Vankelecom Hugo
Published: July 2005

Historically, the study of folliculo-stellate (FS) cells of the anterior pituitary dates back to the onset of electron microscopical observation of the pituitary gland. The morphological and electrophysiological characteristics, topographical distribution and contribution to intercellular junctions of these FS cells have been instrumental to the understanding of their putative function. Moreover, many studies have documented the role of FS cells as a source of newly discovered peptides, growth factors and cytokines. Quantitative immunohistochemical observation of FS cellsin situand functionalin vitrostudies, using either cultured FS cells or cells from an immortalized FS cell line, forwarded the notion of immunophenotypical and functional heterogeneity of the FS cell group. Double immunolabeling with a classical FS cell marker (S-100 protein) and with major histocompatibility complex class II markers characteristic for dendritic cells (DC) have shown a considerable overlap of FS cells with DC. The latter cells are immunocompetent cells belonging to the mononuclear phagocyte system. In this review, the FS cell heterogeneity is discussed with respect to the question of their embryological origin and developmental fate and with respect to the physiological relevance of functionally heterogeneous subpopulations. Recent findings of a myeloid origin of part of the interstitial cells of the anterior pituitary are confronted by other developmental paradigms of pituitary cell differentiation. The possibility that FS cells represent an adult stem cell population of the pituitary is critically examined. Also the physiological role of FS cells in the interferon-γ- and nitric oxide-mediated effects on pituitary hormone secretion is discussed. New approaches for the study of this enigmatic cell group using immortalized cell lines and new markers for an hitherto unrecognized pituitary cell population, the so-called ‘side population’, are evaluated.
Uninsurance and Health Care Access Among Young Adults in the United States
Authors: Callahan S. Todd , Cooper William O.
Published: July 2005

Objective. Young adults who are 19 to 24 years of age are the most likely age group to be uninsured in the United States, yet little is known about how uninsurance might affect health care access among young adults. The objective of this study was to describe the association between health insurance status and health care access among young adults while controlling for other determinants of access to care.

Methods. We conducted a cross-sectional analysis of data from 11 866 19- to 24-year-old respondents who completed the National Health Interview Survey between 1998 and 2001. We present percentages and adjusted relative risk of young adults who in the previous year delayed or missed medical care because of cost, did not fill a prescription because of cost, had not spoken to a health professional, or identified no usual source of health care.

Results. Among the young adults studied, 27% of women and 33% of men were uninsured. After potential confounders were adjusted for, the uninsured remained at significantly higher risk for reporting delayed or missed medical care (women: adjusted relative risk [95% confidence interval]: 3.24 [2.72–3.82]; men: 4.31 [3.44–5.34]), not filling a prescription because of cost (women: 3.27 [2.55–4.16]; men: 4.05 [2.78–5.81]), having no contact with a health professional (women: 2.54 [2.01–3.09]; men: 1.60 [1.43–1.77]), and having no usual source of health care (women: 3.45 [3.05–3.90]; men: 2.27 [2.06–2.48]) relative to privately insured peers. Women with Medicaid did not differ significantly from privately insured women in these measures.

Conclusions. Uninsured young adults were significantly more likely than privately insured peers to report barriers to obtaining needed care, having no contact with a health professional, and identifying no usual source of health care. Given the high rates of uninsurance among young adults, additional study is needed to examine how these barriers affect the immediate and future health of the young adult.