bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the Aromatic Fragment of Piano‐Stool Ruthenium Compounds an Essential Feature for Anticancer Activity? The Development of New RuII‐[9]aneS3Analogues
Authors: Serli Barbara , Zangrando Ennio , Gianferrara Teresa , Scolaro Claudine , Dyson Paul J. , Bergamo Alberta , Alessio Enzo
Published: June 2005

New half‐sandwich RuII‐[9]aneS3complexes ([9]aneS3= 1,4,7‐trithiacyclononane), namely [RuCl2(PTA)([9]aneS3)] (4), [RuCl(PTA)2([9]aneS3)][OTf] (5), [RuCl(en)([9]aneS3)][OTf] (6), [RuCl(enac)([9]aneS3)][OTf] (7), [RuCl(bipy)([9]aneS3)][OTf] (8), and [Ru(dmso‐S)(bipy)([9]aneS3)][OTf]2(9) [PTA = 1,3,5‐triaza‐7‐phosphaadamantane; enac = 1,2‐bis(isopropyleneimino)ethane; OTf = CF3SO3–] were prepared from Ru‐[9]aneS3–dmso precursors and structurally characterized, both in solution and in the solid state by X‐ray crystallography. Some of them are analogs of known cytotoxic organometallic RuII‐(η6‐arene) and RuII‐(η5‐cyclopentadienyl) compounds, in which the aromatic fragment is replaced by the sulfur macrocycle 1,4,7‐trithiacyclononane, while the rest of the coordination sphere is left unchanged. Similarly to the aromatic analogs for which data are available, in aqueous solution the Ru‐[9]aneS3complexes (with the exception of5) hydrolyze a chloride (or a dmso in the case of9) to give the corresponding aquo species. This process is rapidly reversed in the presence of free chloride, and coordination of phosphate is likely to occur to the aquo species in phosphate buffered solutions at physiological pH. Preliminary in vitro tests performed on complexes4–6against the mouse adenocarcinoma cancer cell line (TS/A) and the human mammary normal cell line (HBL‐100) showed that, in general, the Ru‐[9]aneS3compounds have a cytotoxicity comparable to that of the corresponding organometallic analogs. These results suggest that the aromatic fragment of the piano‐stool RuIIcompounds is not an essential feature for the in vitro anticancer activity, and it might be effectively replaced by another face‐capping ligand with a low steric demand, such as [9]aneS3. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Stem cell proteomes: A profile of human mesenchymal stem cells derived from umbilical cord blood
Authors: Feldmann Robert E. , Bieback Karen , Maurer Martin H. , Kalenka Armin , Bürgers Heinrich F. , Gross Benjamin , Hunzinger Christian , Klüter Harald , Kuschinsky Wolfgang , Eichler Hermann
Published: June 2005

Multipotent mesenchymal stem cells (MSCs) derived from human umbilical cord blood (UCB) represent promising candidates for the development of future strategies in cellular therapy. To create a comprehensive protein expression profile for UCB‐MSCs, one UCB unit from a full‐term delivery was isolated from the unborn placenta, transferred into culture, and their whole‐cell protein fraction was subjected to two‐dimensional electrophoresis (2‐DE). Unambiguous protein identification was achieved with peptide mass fingerprinting matrix‐assisted laser desorption/ionization – time of flight – mass spectrometry (MALDI‐TOF‐MS), peptide sequencing (MALDI LIFT‐TOF/TOF MS), as well as gel‐matching with previously identified databases. In overall five replicate 2‐DE runs, a total of 2037 ± 437 protein spots were detected of which 205 were identified representing 145 different proteins and 60 isoforms or post‐translational modifications. The identified proteins could be grouped into several functional categories, such as metabolism, folding, cytoskeleton, transcription, signal transduction, protein degradation, detoxification, vesicle/protein transport, cell cycle regulation, apoptosis, and calcium homeostasis. The acquired proteome map of nondifferentiated UCB‐MSCs is a useful inventory which facilitates the identification of the normal proteomic pattern as well as its changes due to activated or suppressed pathways of cytosolic signal transduction which occur during proliferation, differentiation, or other experimental conditions.
Fused 1,2‐Dithioles. Part VII
Authors: Stachel Hans‐Dietrich , Zimmer Barbara , Eckl Eduard , Semmlinger Katharina , Weigand Wolfgang , Wünsch Ralf , Mayer Peter
Published: June 2005

The 1,2‐dithiolosultam derivative 14 was obtained from the (α‐bromoalkylidene)propenesultam derivative 9 (Scheme 1). Regioselective cleavage of the two ester groups (→1b or 2b) allowed the preparation of derivatives with different substituents at C(3) in the dithiole ring (see 27 and 28) as well as at C(6) in the isothiazole ring (see 17–21; Scheme 2). Curtius rearrangement of the 6‐carbonyl azide 21 in Ac2O afforded the 6‐acetamide 22, and saponification and decarboxylation of the latter yielded ‘sulfothiolutin’ (30). Hydride reductions of two of the bicyclic sultams resulted in ring opening of the sultam ring and loss of the sulfonyl group. Thus the reduction of the dithiolosultam derivative 14 yielded the alkylidenethiotetronic acid derivative 33 (tetronic acid=furan‐2,4(3H,4H)‐dione), and the lactam‐sultam derivative 10 gave the alkylidenetetramic acid derivative 35 (tetramic acid=1,5‐dihydro‐4‐hydroxy‐2H‐pyrrol‐2‐one) (Scheme 3). Some of the new compounds (14, 22, 26, and 30) exhibited antimycobacterial activity. The oxidative addition of 1 equiv. of [Pt(η2‐C2H4)L2] (36a, L=PPh3; 36b, L=1/2 dppf; 36c, L=1/2 (R,R)‐diop) into the SS bond of 14 led to the cis‐(dithiolato)platinum(II) complexes 37a–c. (dppf=1,1′‐bis(diphenylphosphino)ferrocene; (R,R)‐diop={[(4R,5R)‐2,2‐demithyl‐1,3‐dioxolane‐4,5‐diyl]bis(methylene)}bis[diphenylphosphine]).
Trifluoromethanesulfonic Acid Catalyzed Alkylation of Arenes with Methyl (2R)‐Glycidate
Authors: Linares‐Palomino Pablo J. , Prakash G. K. Surya , Olah George A.
Published: June 2005

Methyl (R)‐glycidate (=methyl (R)‐oxiranecarboxylate; 2) in superacidic trifluoromethanesulfonic acid medium reacts with electron‐rich arenes to give α‐hydroxy‐β‐arylpropanoate derivatives 3a–3f with high stereospecificity. At the same time, the observed high regioselectivity has been attributed to superelectrophilic activation of the glycidate.
The exo‐Outstretching Effect Governing the Exclusive Stereoselectivity of the Intramolecular [2+2] Photocycloaddition of Vinylarenes
Authors: Nishimura Jun , Funaki Takashi , Saito Noriaki , Inokuma Seiichi , Nakamura Yosuke , Tajima So , Yoshihara Toshitada , Tobita Seiji
Published: June 2005

Intramolecular [2+2] photocycloaddition of a dimeric vinylpyridine 1 through a singlet‐excited species efficiently formed the corresponding syn‐ and anti‐pyridinophanes 2 and 3. The syn‐isomers were elucidated spectroscopically and by X‐ray crystallography as exo,syn‐configured. The high selectivity under formation of exo,syn‐2 was thoroughly investigated. Consequently, an exo‐outstretching effect, which is observed around the periphery of a face‐to‐face‐oriented system between two aromatic nuclei as a transition state, on cyclobutane ring formation was discovered for the first time.
The Reactivity of 2‐Fluoro‐ and 2‐Chloropyridines toward Sodium Ethoxide: Factors Governing the Rates of Nucleophilic (Het)Aromatic Substitutions
Authors: Schlosser Manfred , Rausis Thierry
Published: June 2005

The relative displacement rates of the halide substituent from 2‐fluoro‐ and 2‐chloropyridines by EtONa in EtOH at +25° were assessed by competition kinetics. The 2‐fluoropyridine reacts 320 times faster than the chloro analog. A CF3 group increases the reactivity more than single halogen atoms do, whatever the element, and the latter are superior to Me3Si groups. Substituents accommodated at the 4‐position operate through their inductive effect, whereas at the 3‐position, this action may be attenuated by steric hindrance. Almost all 5‐substituents enhance the rate of the nucleophilic substitution occurring at the 2‐position. The sole exception concerns the F‐atom at the 5‐position which retards the reaction, presumably by lone‐pair/lone‐pair repulsion with the negative charge building up at the central C‐atom of the intermediate Meisenheimer complex. The substituent effects are additive. Therefore, by using the increments derived from the present work, the rates of future reactions should be predictable with fair accuracy.
Benzo[a]heptalenes from Heptaleno[1,2‐c]furans. Part I
Authors: Uebelhart Peter , Weymuth Christophe , Hansen Hans‐Jürgen
Published: June 2005

It is shown that heptaleno[1,2‐c]furans 1, which are available in two steps from heptalene‐4,5‐dicarboxylates by reduction and oxidative dehydrogenation of the corresponding vicinal dimethanols 2 with MnO2 or IBX (Scheme 4), react thermally in a Diels–Alder‐type [4+2] cycloaddition at the furan ring with a number of electron‐deficient dipolarophiles to yield the corresponding 1,4‐epoxybenzo[d]heptalenes (cf. Schemes 6, 15, 17, and 19). The thermal reaction between dimethyl acetylenedicarboxylate (ADM) and 1 leads, kinetically controlled, via a sterically less‐congested transition state (Fig. 4) to the formation of the (M*)‐configured 1,4‐dihydro‐1,4‐epoxybenzo[a]heptalenes, which undergo a cyclic double‐bond shift to the energetically more‐relaxed benzo[d]heptalenes 4 (Schemes 6 and 7). Most of the latter ones exhibit under thermal conditions epimerization at the axis of chirality, so that the (M*)‐ and (P*)‐stereoisomers are found in reaction mixtures. The (P*)‐configured forms of 4 are favored in thermal equilibration experiments, in agreement with AM1 calculations (Table 1). The relative (P*,1S*,4R*)‐ and (M*,1S*,4R*)‐configuration of the crystalline main stereoisomers of the benzo[d]heptalene‐2,3‐dicarboxylates 4a and 4f, respectively, was unequivocally established by an X‐ray crystal‐structure determination (Figs. 1 and 2). Acid‐induced rearrangement of 4 led to the formation of the corresponding 4‐hydroxybenzo[a]heptalene‐2,3‐dicarboxylates 5 in moderate‐to‐good yields (Schemes 8, 13, and 14). When the aromatization reaction is performed in the presence of trifluoroacetic acid (TFA), trifluoroacetates of type 6 and 13 (Schemes 8, 12, and 13) are also formed via deprotonation of the intermediate tropylium ions of type 7 (Scheme 11). Thermal reaction of 1 with dimethyl maleate gave the 2,3‐exo‐ and 2,3‐endo‐configured dicarboxylates 14 as mixtures of their (P*)‐ and (M*)‐epimers (Scheme 15). Treatment of these forms with lithium di(isopropyl)amide (LDA) at −70° gave the expected benzo[a]heptalene‐2,3‐dicarboxylates 15 in good yields (Scheme 16). Fumaronitrile reacted thermally also with 1 to the corresponding 2‐exo,3‐endo‐ and 2‐endo,3‐exo‐configured adducts 17, again as mixtures of their (P*)‐ and (M*)‐epimers (Scheme 17), which smoothly rearranged on heating in dimethoxyethane (DME) in the presence of Cs2CO3 to the benzo[a]heptalene‐2,3‐dicarbonitriles 18 (Scheme 18). Some cursory experiments demonstrated that hex‐3‐yne‐2,5‐dione and (E)/(Z)‐hexa‐3‐ene‐2,5‐dione undergo also the Diels–Alder‐type cycloaddition reaction with 1 (Scheme 19). The mixtures of the stereoisomers of the 2,3‐diacetyl‐1,4‐epoxytetrahydrobenzo[d]heptalenes 22 gave, on treatment with Cs2CO3 in DME at 80°, only mixtures of the regioisomeric inner aldol products 24 and 25 of the intermediately formed benzo[a]heptalenes 23 (Scheme 20).
Synthetic Route to Ergot Alkaloids
Authors: Moldvai István , Temesvári‐Major Eszter , Incze Mária , Dörnyei Gábor , Szentirmay Éva , Szántay Csaba
Published: June 2005

Rye is sometimes infected by a fungus called Claviceps purpurea. The term ergot designates the dark, brown, tuberous bodies which can be collected before or during harvesting and represent one of the most remarkable drugs of our therapeutic arsenal. Actually, the most significant alkaloids are metabolic products of these fungi. We elaborated three alternative total synthetic pathways to construct the ergoline skeleton, one of which – suitable for scaling up – finally resulted in (+)‐lysergic acid (32a) and α‐ergocryptine (1) (Schemes 5 and 6).
The Thermolysis of the Cycloadducts between Aryl Azides and Hexamethyl‐Dewar‐Benzene Revisited
Authors: Christl Manfred , Lesch Steffen , Deuerlein Stephan , Stalke Dietmar
Published: June 2005

The reactions of 1‐azido‐2,4,6‐trimethyl‐ and 1‐azido‐2,6‐dimethylbenzene with hexamethyl‐Dewar‐benzene (HMDB) give rise to the pentamethyl(iminoethyl)‐4H‐1,2‐diazepines 4 and 5, respectively. The X‐ray crystal‐structure analysis of 5 unequivocally established these unexpected structures, which motivated us to re‐investigate the thermolysis of the adduct 1a of HMDB and azidobenzene. Previously, the triazonine 2 was reported to be the major product, but this interpretation could not be corroborated now, and, instead, the 1‐aminopyrrole 6 was identified as the true compound. The structure of the analogous compound 7, obtained by thermolysis of the (1‐azido‐4‐nitrobenzene)‐HMDB adduct 1b, was confirmed by X‐ray diffraction. In the original literature investigation, a second product had been isolated, in addition to the alleged 2, by chromatographic purificiation of the thermolysis mixture, and structure 3 had been ascribed to it. It turns out now that this compound is not a valence isomer of the major product, but a hydrolysis product, i.e., the ketone 8. The formation of the rather different compounds 4 and 5 on the one hand, and 6 and 7 on the other hand, can be rationalized straightforwardly by a sequence of pericyclic reactions leading to 3H‐1,2‐diazepines 11 as common intermediates, which are converted to either 4 and 5, or 6 and 7, depending on the nature of the aromatic group.
Reversal of Regioselectivity of Nitrone Cycloadditions by Lewis Acids
Authors: Dugovič Branislav , Fišera Lubor , Cyranski Michal K. , Hametner Christian , Prónayová Nada , Obranec Marián
Published: June 2005

The regio‐ and stereoselectivity of cycloadditions of the nitrone 1a and the chiral, sugar‐derived nitrones 13a and 13b with 3‐(prop‐2‐enoyl)‐1,3‐oxazolidin‐2‐one (2) depends on the nature of the Lewis acid catalyst used. Addition of Lewis acid reverses the regioselectivity of the cycloaddition, and improves the anti‐diastereoselectivity in the case of chiral nitrones. The sterically favored isoxazolidin‐5‐yl‐substituted adducts 3, 4, and 14–17 are produced as the major products in the absence of Lewis acid, while the electronically favored regioisomers with isoxazolidin‐4‐yl substituents (5, 6, and 18–21, respectively) are obtained as major products in the [Ti(OiPr)2Cl2] catalyzed reactions. The reactions of nitrone 13b with 2 in the presence of other Lewis acids such as ZnCl2, ZnBr2, ZnI2 and MgI2/I2 gave both regioisomeric pairs of the diastereoisomers, favoring the 4‐substituted congeners. The diastereoisomeric isoxazolidines 3a–6a were reduced with NaBH4 in THF/H2O with subsequent desilylation to yield the separable diols 9–12. Reduction of the diastereoisomeric isoxazolidines 19a and 18a afforded the chiral alcohols 23 and 22, the latter of which was analyzed by X‐ray crystallography.
The Relationship of Cycloaddition Reactions to Spontaneous Vinyl Polymerizations
Authors: Hall Henry K. , Buyle Padias Anne
Published: June 2005

The zwitterionic–biradical tetramethylene proposed by Huisgen as the key intermediate in stepwise [2+2] cycloaddition reactions has been shown to be the crucial intermediate in spontaneous vinyl polymerizations as well. Predominantly biradical tetramethylenes initiate free‐radical copolymerizations, while predominantly zwitterionic tetramethylenes initiate cationic or anionic homopolymerizations. Stepwise cycloaddition is viewed as a spontaneous polymerization lacking a propagation step. These tendencies could be correlated in the form of an ‘organic chemist's Periodic Table’, which has recently been put on a quantitative basis.

Huisgen also showed experimentally that [4+2] Woodward–Hoffman‐allowed cycloadditions are completely concerted. Spontaneous copolymerizations accompanying these cycloadditions, therefore, were ascribed to the s‐trans diene form. This concept was given support by kinetics studies, as well as by exclusive cycloaddition from s‐cis cyclopentadiene, and exclusive copolymerization from s‐trans verbenene.
[2+2] Cycloaddition Reactions of Imines with Cyclic Ketenes: Synthesis of 1,3‐Thiazolidine Derived Spiro‐β‐lactams and Their Transformations
Authors: Cremonesi Giuseppe , Dalla Croce Piero , La Rosa Concetta
Published: June 2005

Unsymmetric cyclic ketenes were generated from N‐acyl‐1,3‐thiazolidine‐2‐carboxylic acids 1a–c by means of Mukaiyama's reagent, and then reacted with imines 2a–c to the new, isomeric spiro‐β‐lactams 3 and 4 via [2+2] cycloaddition (Staudinger ketene–imine reaction; Scheme 1). The reactions were stereoselective (Table 1) and mainly afforded the spiro‐β‐lactams with a relative trans configuration. The spiro‐β‐lactams could be transformed into the corresponding monocyclic β‐lactams by means of thiazolidine ring opening or into substituted thiazolidines via hydrolysis of the β‐lactam ring.
Exploring the Border between Concerted and Two‐Step Pathways of 1,3‐Dipolar Cycloadditions of Organic Azides to Cyclic Ketene N,X‐Acetals. – Synthesis and 15N‐NMR Spectra of Zwitterions and Spirocyclic Cycloadducts
Authors: Quast Helmut , Ach Manfred , Balthasar Jürgen , Hergenröther Thomas , Regnat Dieter , Lehmann Jens , Banert Klaus
Published: June 2005

Cyclic ketene N,X‐acetals 1 are electron‐rich dipolarophiles that undergo 1,3‐dipolar cycloaddition reactions with organic azides 2 ranging from alkyl to strongly electron‐deficient azides, e.g., picryl azide (2L; R1=2,4,6‐(NO2)3C6H2) and sulfonyl azides 2M–O (R1=XSO2; cf. Scheme 1). Reactions of the latter with the most‐nucleophilic ketene N,N‐acetals 1A provided the first examples for two‐step HOMO(dipolarophile)–LUMO(1,3‐dipole)‐controlled 1,3‐dipolar cycloadditions via intermediate zwitterions 3. To set the stage for an exploration of the frontier between concerted and two‐step 1,3‐dipolar cycloadditions of this type, we first describe the scope and limitations of concerted cycloadditions of 2 to 1 and delineate a number of zwitterions 3. Alkyl azides 2A–C add exclusively to ketene N,N‐acetals that are derived from 1H‐tetrazole (see 1A) and 1H‐imidazole (see 1B,C), while almost all aryl azides yield cycloadducts 4 with the ketene N,X‐acetals (X=NR, O, S) employed, except for the case of extreme steric hindrance of the 1,3‐dipole (see 2E; R1=2,4,6‐(tBu)3C6H2). The most electron‐deficient paradigm, 2L, affords zwitterions 16D,E in the reactions with 1A, while ketene N,O‐ and N,S‐acetals furnish products of unstable intermediate cycloadducts. By tuning the electronic and steric demands of aryl azides to those of ketene N,N‐acetals 1A, we discovered new borderlines between concerted and two‐step 1,3‐dipolar cycloadditions that involve similar pairs of dipoles and dipolarophiles: 4‐Nitrophenyl azide (2G) and the 2,2‐dimethylpropylidene dipolarophile 1A (R, R=H, tBu) gave a cycloadduct 13 H, while 2‐nitrophenyl azide (2 H) and the same dipolarophile afforded a zwitterion 16A. Isopropylidene dipolarophile 1A (R=Me) reacted with both 2G and 2 H to afford cycloadducts 13G,J) but furnished a zwitterion 16B with 2,4‐dinitrophenyl azide (2I). Likewise, 1A (R=Me) reacted with the isomeric encumbered nitrophenyl azides 2J and 2K to yield a cycloadduct 13L and a zwitterion 16C, respectively. These examples suggest that, in principle, a host of such borderlines exist which can be crossed by means of small structural variations of the reactants. Eventually, we use 15N‐NMR spectroscopy for the first time to characterize spirocyclic cycloadducts 10–14 and 17 (Table 6), and zwitterions 16 (Table 7).
A path from Ih to C1 symmetry for C20 cage molecule
Authors: Wang Zhigang , Lian Keyan , Pan Shoufu , Fan Xianhong
Published: June 2005

The symmetry of the C20 cage is studied based on the intrinsical relationship among point groups (Bradley, C. J.; Cracknell, A. P. The Mathematical Theory of Symmetry in Solids; Claredon Press: Oxford, 1972). The structure of the C20 cage with Ih symmetry is constructed, as are eight other structures with subgroup symmetry. A path from Ih symmetry to C1 symmetry is obtained for the closed‐shell electronic state, and the structure with D2h symmetry is the most stable on this path. Using the D2h structure the correlation energy correction is studied on the condition of restricted excitation space at the CCSD(T) level. We obtain curves on the relation between the orbital numbers and the total energy at the CCSD(T), CCSD, and MP2 level, respectively. The results of these curves obtained from MP2 and CCSD(T) methods have the same tendency, while the results of CCSD gradually diverge with an increase in orbital numbers. When the orbitals used in the calculation reach 460, the total energy is −759.644 hartree at MP2 level and is −759.721 hartree by the CCSD(T) method. From the calculation results, we find that a large basis set can improve the reliability of the MP2 method, and to restrict excitation space is necessary when using the CCSD(T) method. © 2005 Wiley Periodicals, Inc. J Comput Chem 12: 1279–1283, 2005
Effects of temperature and water on critical oxygen tension of turtle embryos
Authors: Kam Yeong‐Choy , Lillywhite Harvey B.
Published: June 2005

The influences of temperature and water on the ability of turtle embryos to tolerate hypoxia were investigated by measuring critical oxygen tension, Pc, at different levels of temperature (22, 27, and 32°C) and hydric conditions (3 and 13% gravimetric water content). Eggs were half‐buried in sand with 3 or 13% gravimetric water content and incubated at a constant 30°C. Using a closed metabolic chamber, oxygen consumption, \documentclass{article}\pagestyle{empty}\begin{document}$ \mathop {\rm V}\limits^{\rm .} $\end{document}, was measured at decreasing oxygen tensions. Embryonic \documentclass{article}\pagestyle{empty}\begin{document}$ \mathop {\rm V}\limits^{\rm .} $\end{document} varied as a function of incubation day and temperature, whereas the Pc differed among temperatures but not among incubation days. At a given incubation day, the Pc increased in direct proportion to temperature. Eggs incubated in sand with 13% gravimetric water content achieved greater mass at days 30 and 39 than did those in sand with 3% gravimetric water content. However, \documentclass{article}\pagestyle{empty}\begin{document}$ \mathop {\rm V}\limits^{\rm .} $\end{document}, Pc, and masses of yolk‐free hatchlings were similar in the two hydric conditions, indicating that hypoxic tolerance of turtle eggs is not curtailed by excessive water absorption. The similarity in Pc is likely attributable to the small \documentclass{article}\pagestyle{empty}\begin{document}$ \mathop {\rm V}\limits^{\rm .} $\end{document}/surface area ratio of turtle eggs. Within the range of parameters studied, temperature, but not water, can modify the Pc of turtle embryos. © 1994 Wiley‐Liss, Inc.
Serial repetition of cilia pairs along the tail surface of an ascidian larva
Authors: Crowther Robert J. , Whittaker J. R.
Published: June 2005

Regularly spaced cilia pairs were found in two rows immediately opposite to each other mid‐dorsally and mid‐ventrally along the larval tail surface of the ascidian protochordate Ciona intestinalis. There were approximately ten such equidistantly placed dorsal‐ventral sets embedded in the matrix of the extracellular larval test which forms the flattened vertical tail fin. These immotile cilia originate from pairs of cell bodies in mid‐dorsal and mid‐ventral peripheral nerves running beneath the tail epidermis. The cilia and neural cell bodies were visualized by immunocytochemical staining with anti‐tubulin antibodies; their nature was confirmed by ultrastructural examination. This pattern of cilia and neural cell body placement is conceivably related to the segmentation found in vertebrates. © 1994 Wiley‐Liss, Inc.
Effect of exogenous estradiol applied at different embryonic stages on sex determination, growth, and mortality in the leopard gecko (Eublepharis macularius)
Authors: Tousignant Alan , Crews David
Published: June 2005

Temperature‐dependent sex determination (TSD) occurs in three orders of reptiles. Several studies have examined the ability of estradiol to produce female hatchlings incubated at a male‐producing temperature. The results of these experiments support the idea that estradiol could be used as a powerful tool in the conservation of endangered species with TSD by manipulating hatchling sex ratios. However, these experiments have concentrated on the mechanism of determination. This experiment was designed to test the efficacy of various dosages of estradiol applied at two different stages to alter the hatchling sex ratio as well as determining the potential use of such manipulation for conservation efforts by monitoring egg mortality and hatchling growth. The leopard gecko (Eublepharis macularius) exhibits TSD and reaches reproductive maturity in less than one year, making it an excellent model for evaluating the long‐term effects of estradiol. The results demonstrate that estradiol has a dose‐dependent effect on the hatchling sex ratio while only high dosages applied at the later stage of development showed increased mortality. Estrogen‐determined females grew at the same rate as temperature‐determined females and have produced viable hatchlings. Estradiol treatment of eggs from endangered species may provide a method of insuring female offspring when the TSD pattern is unknown or equipment for controlled incubation is unavailable. © 1994 Wiley‐Liss, Inc.
Development of in vitro organ culture techniques for differentiation and growth of cartilages and bones from teleost fish and comparisons with in vivo skeletal development
Authors: Miyake Tsutomu , Hall Brian K.
Published: June 2005

To examine molecular and cellular mechanisms of fish skeletogenesis, an in vitro organ culture system was developed to achieve effective maintenance, growth, and/or differentiation of embryonic skeletal tissues from Oryzias latipes (Japanese ricefish) and Brachydanio rerio (zebra‐fish). In vivo and in vitro skeletogenesis were compared. The techniques developed here open the way for descriptive and experimental in vitro analyses of fish skeletogenesis. The present study found that submerged organ culture using medium 199 or Leibovitz's L‐15, supplemented with fetal bovine serum and ascorbic acid, was most suitable. Supplementation with antibiotic‐antimycotics prevented microbial contamination, especially during explant preparation. Two types of inorganic membrane substrates did not produce different results from culture on plastic Falcon dishes; all sustained healthy embryonic skeletal explants. The present system sustained maintenance, growth, or de novo differentiation of embryonic skeletal tissues, when compared with in vivo formation and growth of the embryonic cranial skeletons in the two species. Already formed bones (parasphenoid, opercule and/or branchiostegal rays) and cartilages were successfully maintained and/or grew in culture. Both perichondral bone (around gill arches, hyosymplecticum, hyoid arch, Meckel's cartilage) and membrane bone (dentary) differentiated de novo, but did not mineralize. De novo hypertrophy of chondrocytes was observed in some cartilages as occurs in normal development. Although already formed teeth were maintained, de novo differentiation of teeth was not observed in vitro, suggesting that mandibular and gill perichondral bones may form independently of tooth formation.
Estradiol‐17β associated with the sex reversal in protandrous black porgy, Acanthopagrus schlegeli
Authors: Chang Ching‐Fong , Lee Mong‐Fong , Chen Guan‐Ru
Published: June 2005

The objectives of this study were to investigate the seasonal changes of steroid profiles, estradiol‐17β (E2), testosterone (T), and 17α‐hydroxyprogesterone (17α‐OH P), among female, male, and reversing female black porgy, Acanthopagrus schlegeli. The experimental induction of sex reversal in juvenile black porgy by exogenous E2 was also studied. Three‐year‐old male (n = 8) and four‐year‐old female (n = 7) black porgy were selected for the experiment of seasonal changes of steroid profiles. Blood samples were collected from each fish at 2 week intervals for 8 months. Plasma samples in three‐year‐old males were further classified to those of males (n = 4) and reversing females (n = 4) based on the sexual stage of the gonad at the end of the experiment. Plasma E2 profiles in males were significantly different from those in the reversing females. Peak levels of plasma E2 in the females and reversing females occurring during the early prespawning season were similar. Lower levels of plasma E2 were, however, observed in the males. Plasma T did not differ significantly in females, males or reversing females. Low and constant levels of plasma 17α‐OH P were observed in each group of fish. In the experimental induction of sex reversal, oral administration of E2 (4 mg per kg of feed) for 5 months suppressed the spermiation and inhibited gonadal growth but successfully induced the precocious sex change at the prespawning stage in one‐year‐old black porgy. Ovarian tissue with primary oocytes was predominant in the gonads of E2‐fed fishes. Our data suggest that high levels of plasma E2 in the prespawning and spawning season are likely correlated with the natural sex reversal of black porgy. E2 likely plays an important role in sex reversal of protandrous black porgy. © 1994 Wiley‐Liss, Inc.
Plasma levels of eggshell zr‐proteins, estradiol‐17β, and gonadotropins during an annual reproductive cycle of Atlantic salmon (Salmo salar)
Authors: Oppen‐Berntsen D. O. , Olsen S. O. , Rong C. J. , Taranger G. L. , Swanson P. , Walther B. T.
Published: June 2005

Eggshell zona radiata proteins (zr‐proteins) were found to occur normally in plasma of sexually mature female (but not male) Atlantic salmon (Salmon salar). In order to ascertain the physiological relevance of these findings, we developed a specific enzyme‐linked immunoassay for zr‐proteins and screened plasma from sexually maturing Atlantic salmon females throughout an annual reproductive cycle. While zr‐proteins were detectable at low levels in female adult salmon plasma prior to sexual maturation, zr‐protein levels increased dramatically as sexual maturation proceeded. The strong correlation between gonado‐somatic index (GSI) and plasma zr‐proteins indicates a reproductive role for blood borne zr‐proteins. During the vitellogenic phase, levels of plasma zr‐proteins were positively correlated with GSI and with plasma levels of gonadotropin I (GtH I) and estradiol‐17β, as determined by radioimmuno‐assays. However, during final sexual maturation, only the plasma level of gonadotropin II (GtH II) was positively correlated to GSI. In contrast, zr‐proteins and estradiol‐17β were both negatively correlated to plasma level of GtH II during this period. In view of estradiol‐17β‐induced hepatic synthesis and secretion of zr‐proteins (Oppen‐Berntsen et al.: Journal of Endocrinology 135:293–302, 1992a) and the established role of gonadotropins in regulating ovarian estradiol synthesis, we interpret the observed correlations among plasma levels of GtH I, estradiol‐17β and zr‐proteins in Atlantic salmon to signify that GtH I regulates ovarian estradiol‐17β synthesis, which in turn regulates hepatic synthesis and secretion of both vitellogenin and zr‐proteins during oogenesis. © 1994 Wiley‐Liss, Inc.
Effects of spatial and temporal resolution for MR image‐guided thermal ablation of prostate with transurethral ultrasound
Authors: Pisani Laura J. , Ross Anthony B. , Diederich Chris J. , Nau William H. , Sommer F. Graham , Glover Gary H. , Butts Kim
Published: June 2005

Purpose

To describe approaches for determining optimal spatial and temporal resolutions for the proton resonance frequency shift method of quantitative magnetic resonance temperature imaging (MRTI) guidance of transurethral ultrasonic prostate ablation.

Materials and Methods

Temperature distributions of two transurethral ultrasound applicators (90° sectored tubular and planar arrays) for canine prostate ablation were measured via MRTI during in vivo sonication, and agree well with two‐dimensional finite difference model simulations at various spatial resolutions. Measured temperature distributions establish the relevant signal‐to‐noise ratio (SNR) range for thermometry in an interventional MR scanner, and are reconstructed at different resolutions to compare resultant temperature measurements. Various temporal resolutions are calculated by averaging MRTI frames.

Results

When noise is added to simulated temperature distributions for tubular and planar applicators, the minimum root mean squared (RMS) error is achieved by reconstructing to pixel sizes of 1.9 and 1.7 mm, respectively. In in vivo measurements, low spatial resolution MRTI data are shown to reduce the noise without significantly affecting thermal dose calculations. Temporal resolution of 0.66 frames/minute leads to measurement errors of more than 12°C during rapid heating.

Conclusion

Optimizing MRTI pixel size entails balancing large pixel SNR gain with accuracy in representing underlying temperature distributions. J. Magn. Reson. Imaging 2005;22:109–118. © 2005 Wiley‐Liss, Inc.
Importance of bone‐conducted sound transmission on patient hearing in the MR scanner
Authors: Moelker Adriaan , Maas Ronald A.J.J. , Vogel Mika W. , Ouhlous Mohamed , Pattynama Peter M.T.
Published: June 2005

Purpose

to evaluate the influence of bone‐conduction in the MR environment compared to a standardized acoustic environment.

Materials and Methods

Acoustic noise is an unwanted side effect of MRI that is commonly tackled with passive hearing protection. In an MR scanner, however, with the patient completely surrounded by the MR sounds and in close contact with the vibrating MR table and gantry, bone‐conduction may increase subjective sound levels, restricting the efficacy of passive protection that reduces air‐conducted noise only. A total of 10 volunteers were subjected to pure MR tones, covering the frequency range relevant for hearing and at 60 dB, generated through the MR system's gradient coils. Bone‐conduction was determined for various passive damping conditions in an MR scanner and was compared to that acquired in an acoustically‐calibrated environment. The contribution of mechanical vibrations to bone‐conduction was determined. Also, with a microphone in the ear canal, the objective efficacy of the passive protection was measured.

Results

We found no difference between the bone‐conduction experiments executed inside the imager and in the acoustically‐controlled environment. The overall insertion loss of the passive hearing protectors was over 20 dB with strongest effects at 0.4 and 2.5 kHz.

Conclusion

As bone‐conduction is not more pronounced inside the MR scanner than outside, the previous reports on the subjective evaluation of protection devices in MRI hold their validity. J. Magn. Reson. Imaging 2005;22:163–169. © 2005 Wiley‐Liss, Inc.
Apparent diffusion coefficient measurements with diffusion‐weighted magnetic resonance imaging for evaluation of hepatic fibrosis
Authors: Koinuma Miwa , Ohashi Isamu , Hanafusa Kaoru , Shibuya Hitoshi
Published: June 2005

Purpose

To evaluate the use of apparent diffusion coefficient (ADC) measurements based on diffusion‐weighted MRI (DWI) to assess stage of liver disease.

Materials and Methods

A total of 31 patients who underwent both a liver biopsy and DWI and 132 patients who only underwent DWI were enrolled. Biopsy specimens were scored for fibrosis and necroinflammation according to the Knodell histology activity index (HAI). The 31 patients consisted of 21 patients with chronic hepatitis and 10 with cirrhosis (Child‐Pugh stage A in nine and stage B in one), and the 132 patients consisted of 56 patients with cirrhosis (Child‐Pugh stage A in 41, stage B in 10, and stage C in five), 42 with chronic hepatitis, and 34 with normal liver function. The ADCs in the liver parenchyma were measured using DWI with relatively low b factors (b = 0.01 and 128.01 seconds/mm2) and were compared among the HAI scores and among patients with cirrhosis, chronic hepatitis, and normal liver function.

Results

The ADCs decreased as the fibrosis score in the HAI increased, and the correlation was statistically significant (P < 0.0001). No relationship between the ADCs and the necroinflammation scores in the HAI was found. The ADCs decreased as the stage of liver disease progressed or as the Child‐Pugh stage progressed, and these relationships were statistically significant (P < 0.0001).

Conclusion

ADC measurements are potentially useful for the evaluation of fibrosis staging in the liver. J. Magn. Reson. Imaging 2005;22:80–85. © 2005 Wiley‐Liss, Inc.
Local staging of rectal carcinoma and assessment of the circumferential resection margin with high‐resolution MRI using an integrated parallel acquisition technique
Authors: Oberholzer Katja , Junginger Theodor , Kreitner Karl‐F. , Krummenauer Frank , Simiantonaki Nektaria , Trouet Susan , Thelen Manfred
Published: June 2005

Purpose

To assess the diagnostic accuracy of integrated parallel acquisition technique (iPAT) in local staging of rectal carcinoma in comparison to conventional high‐resolution MRI.

Materials and Methods

A total of 28 patients with a neoplasm of the rectum and 15 control patients underwent MRI of the pelvis. High‐resolution images were acquired conventionally and with iPAT using a modified sensitivity encoding (mSENSE). Image quality, signal‐to‐noise and contrast‐to‐noise ratios (SNR, CNR), tumor extent, nodal status, and delineation of the circumferential resection margin (CRM) were compared. In 19 patients with a carcinoma, MR findings were correlated with the histopathological diagnosis. Tumor distance to the CRM was matched with resection specimen in 12 cases.

Results

The comparison of both MR techniques revealed no clinically relevant differences in tumor staging and delineation of the CRM, though SNR and CNR were significantly lower in mSENSE images. Tumor stage was concordant in 17 of 19 cases compared to histopathology. In four of nine patients with T3 and T4 carcinomas, the histopathological resection margin was ≤2 mm, in five cases MRI predicted a margin of ≤2 mm.

Conclusion

The application of iPAT in local staging of rectal carcinoma is time‐saving and does not degrade diagnostic accuracy. Tumor stage, nodal status, and the CRM can be assessed equally compared to conventional acquisition techniques. J. Magn. Reson. Imaging 2005;22:101–108. © 2005 Wiley‐Liss, Inc.
MRI in Crohn's disease
Authors: Horsthuis Karin , Lavini Cristina , Stoker Jaap
Published: June 2005

Technological developments have extended the role of MRI in the evaluation of the gastrointestinal tract. The potential of MRI to evaluate disease activity in Crohn's disease has been investigated extensively, as MRI has intrinsic advantages over other techniques, including noninvasiveness and the absence of ionizing radiation. For perianal fistulizing disease MRI has become a mainstay in evaluation of disease, as localization and extent of disease can be very well appreciated using both T2‐weighted and T1‐weighted sequences, fat suppression, and intravenous contrast medium. Imaging of the small bowel and colon in Crohn's disease is more complicated due to bowel peristalsis and respiratory movement. However, using fast breathhold sequences and intravenous spasmolytic medication, images of good diagnostic quality can be acquired. To obtain sufficiently distended bowel, which in our estimation is a prerequisite for evaluation of the bowel, MR enteroclysis can be performed. However, applicability of different oral contrast media has been studied, as a noninvasive method for bowel distension would be preferable. Abdominal MRI is a valuable imaging technique for evaluation of luminal, transmural, and extraintestinal manifestations of Crohn's disease as degree of disease activity, presence of luminal pathology (e.g., stenoses), and extraintestinal manifestations of disease (e.g., abscesses, fistulas) can be accurately assessed. J. Magn. Reson. Imaging 2005;22:1–12. © 2005 Wiley‐Liss, Inc.
Routine clinical brain MRI sequences for use at 3.0 Tesla
Authors: Lu Hanzhang , Nagae‐Poetscher Lidia M. , Golay Xavier , Lin Doris , Pomper Martin , van Zijl Peter C.M.
Published: June 2005

Purpose

To establish image parameters for some routine clinical brain MRI pulse sequences at 3.0 T with the goal of maintaining, as much as possible, the well‐characterized 1.5‐T image contrast characteristics for daily clinical diagnosis, while benefiting from the increased signal to noise at higher field.

Materials and Methods

A total of 10 healthy subjects were scanned on 1.5‐T and 3.0‐T systems for T1 and T2 relaxation time measurements of major gray and white matter structures. The relaxation times were subsequently used to determine 3.0‐T acquisition parameters for spin‐echo (SE), T1‐weighted, fast spin echo (FSE) or turbo spin echo (TSE), T2‐weighted, and fluid‐attenuated inversion recovery (FLAIR) pulse sequences that give image characteristics comparable to 1.5 T, to facilitate routine clinical diagnostics. Application of the routine clinical sequences was performed in 10 subjects, five normal subjects and five patients with various pathologies.

Results

T1 and T2 relaxation times were, respectively, 14% to 30% longer and 12% to 19% shorter at 3.0 T when compared to the values at 1.5 T, depending on the region evaluated. When using appropriate parameters, routine clinical images acquired at 3.0 T showed similar image characteristics to those obtained at 1.5 T, but with higher signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR), which can be used to reduce the number of averages and scan times. Recommended imaging parameters for these sequences are provided.

Conclusion

When parameters are adjusted for changes in relaxation rates, routine clinical scans at 3.0 T can provide similar image appearance as 1.5 T, but with superior image quality and/or increased speed. J. Magn. Reson. Imaging 2005;22:13–22. © 2005 Wiley‐Liss, Inc.
Apparent diffusion coefficient and fractional anisotropy in spinal cord: Age and cervical spondylosis–related changes
Authors: Mamata Hatsuho , Jolesz Ferenc A. , Maier Stephan E.
Published: June 2005

Purpose

To present the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) change with age in the normal spinal cord and in cervical spondylosis.

Materials and Methods

A total of 11 normal volunteers and 79 cervical spondylosis patients entered this study. Line scan diffusion tensor images were obtained in a 1.5‐Tesla whole‐body scanner using a phased‐array spine coil. The ADC and FA values were measured on a sagittal section. Spearman correlation of ADC/FA vs. age for normal spinal cord was calculated.

Results

The mean ADC of the normal spinal cord was 0.81 ± 0.03 μm2/msec at the relatively wide C2–C3 level and 0.75 ± 0.06 μm2/msec at the more narrow C4–C7 level. The FA at the corresponding level was 0.70 ± 0.05 and 0.66 ± 0.03, respectively. With age, ADC showed positive correlation (Spearman, r = 0.242) and FA exhibited negative correlation (Spearman, r = −0.244). A total of 54% of all spondylosis cases showed elevated ADC (P < 0.001) and decreased FA (P < 0.001) at the stenotic spinal canal level compared with the normal spinal cord. The average ADC and FA of high‐signal lesions on T2‐weighted images (seven patients) were 1.28 ± 0.33 μm2/msec and 0.46 ± 0.12, respectively.

Conclusion

ADC increases and FA decreases with age in the normal spinal cord. Elevated ADC and reduced FA were measured in the spinal cord of spondylosis cases with clinical symptoms of myelopathy. J. Magn. Reson. Imaging 2005;22:38–43. © 2005 Wiley‐Liss, Inc.
Single‐breathhold, four‐dimensional, quantitative assessment of LV and RV function using triggered, real‐time, steady‐state free precession MRI in heart failure patients
Authors: Narayan Girish , Nayak Krishna , Pauly John , Hu Bob
Published: June 2005

Purpose

To validate a novel, real‐time, steady‐state free precession (SSFP), single‐breathhold technique for the assessment of left ventricular (LV) and right ventricular (RV) function in heart failure patients.

Materials and Methods

A total of 20 heart failure patients (mean age 59 ± 17 years) underwent scanning with our new, real‐time, spiral SSFP sequence in which each cardiac phase was acquired in 118 msec at a resolution of 1.8 × 1.8 mm. Each cardiac slice (1‐cm thick) was automatically advanced based on a cardiac trigger, allowing complete coverage of the heart in a single breathhold. The patients also underwent LV and RV assessment with the gold standard: multiple breathhold, cardiac‐gated, segmented k‐space strategy. LV and RV end‐systolic volume (ESV) and end‐diastolic volume (EDV) and LV mass were compared between the two imaging techniques.

Results

The new real‐time strategy was highly concordant with the gold standard technique in the assessment of LVEDV (r = 0.98), LVESV (r = 0.98), RVESV (r = 0.86), RVEDV (r = 0.91), LVMASS (r = 0.95), RVEF (r = 0.70), and LVEF (r = 0.94). The mean bias (95% confidence interval [CI]) for each parameter is LVEDV: 10.6 cc (cm3) (3.8–17.4 cc), LVESV: −0.8 cc (−5.3 to 3.7 cc), RVEDV: 3.7 cc (−5.6 to 13.2 cc), RVESV: −3.1 cc (−11.1 to 4.9 cc), LVMASS: 26 g (12.4–39.8 g), RVEF: −2.9% (1.3 to −7.2 %), LVEF: 1.9% (5 to −1.1%). In addition, data acquisition was only nine ± two seconds with the real‐time strategy vs. 312 ± 41 seconds for the standard technique.

Conclusion

In patients with heart failure, real‐time, spiral SSFP allows rapid and accurate assessment of RV and LV function in a single‐breath hold. Using the same strategy, increased temporal resolution will allow real‐time assessment of cardiac wall motion during stress studies. J. Magn. Reson. Imaging 2005;22:59–66. © 2005 Wiley‐Liss, Inc.
Correction of phase offset errors in main pulmonary artery flow quantification
Authors: Lankhaar Jan‐Willem , Hofman Mark B.M. , Marcus J. Tim , Zwanenburg Jaco J.M. , Faes Theo J.C. , Vonk‐Noordegraaf Anton
Published: June 2005

Purpose

To investigate whether an existing method for correction of phase offset errors in phase‐contrast velocity quantification is applicable for assessment of main pulmonary artery flow with an MR scanner equipped with a high‐power gradient system.

Materials and Methods

The correction method consists of fitting a surface through the time average of stationary pixels of velocity‐encoded phase images, and subtracting this surface from the velocity images. Pixels are regarded as stationary if their time standard deviation falls into the lowest percentile. Flow was measured in the main pulmonary artery of 15 subjects. Each measurement was repeated on a stationary phantom. The phase offset error in the phantom was used as a reference. Correction was applied with varying polynomial surface orders (0–5) and stationarity percentiles (5–50%). The optimal surface order and stationarity percentile were determined by comparing the fitted surface with the phantom.

Results

Using a first‐order surface and a (noncritical) 25% percentile, the correction method significantly reduced the phase offset error from 1.1 to 0.35 cm/second (RMS), which is equivalent to a reduction from 11% to 3.3% of mean volume flow. Phase error correction strongly affected stroke volume (range –11 to 26%).

Conclusion

The method significantly reduces phase offset errors in pulmonary artery flow. J. Magn. Reson. Imaging 2005;22:73–79. © 2005 Wiley‐Liss, Inc.