bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convenient synthesis of [2‐14C]‐methylglyoxal bis(guanylhydrazone), [14C]‐mitoguazone
Authors: Burgos Alain , Ellames George J. 
Published: October 2006

Abstract[2‐14C]‐Methylglyoxal bis(guanylhydrazone) dihydrochloride, [14C]‐mitoguazone, 3, has been prepared in three steps from potassium [1‐14C]‐acetate in an overall radiochemical yield of 16%. The key steps in this procedure are the formation of the sodium salt of [acetone‐2‐14C]‐methylsulfinylacetone, 5, and Pummerer rearrangement to the [14C] labelled hemithioacetal, 6, which is trapped with two equivalents of aminoguanidine to afford the desired [14C] mitoguazone, 3.
Synthesis of the enantiomers of [3‐3H]‐2‐[[4‐[(7‐chloro‐4‐quinolinyl)‐amino]pentyl]ethylamino]ethanol, [3‐3H]‐hydroxychloroquine
Authors: Ellames George J. , Herbert John M. , Peace James E. , Smith David I. , Wedge Karen J. 
Published: October 2006

AbstractThe enantiomers of [3‐3H]‐2‐[[4‐[(7‐chloro‐4‐quinolinyl)amino]pentyl]ethylamino]ethanol,[3‐3H]‐hydroxychloroquine, (R)‐8 and (S)‐8, have been prepared in two steps from the known precursors 4,7‐dichloro‐3‐iodoquinoline,4, and the enantiomers of 2‐[(4‐aminopentyl)ethylamino]ethanol, (R)‐2 and (S)‐2, by formation of the enantiomers of 2‐[[4‐[(7‐chloro‐3‐iodo‐4‐quinolinyl)amino]pentyl]ethylamino]ethanol, (R)‐3 and (S)‐3, and subsequent reductive deiodination with tritium gas over 10% palladium on charcoal.
Synthesis and NMR characterization of selectively 15N‐labelled trans‐ and cis‐butenediamido‐linked bis‐netropsins
Authors: Plouvler Bertrand , Singh Malvinder P. , Lown J. William 
Published: October 2006

AbstractThe synthesis of specifically 15N labelled trans‐ and cis‐isomers of bis‐netropsins derived from 2‐butene‐1,4‐dicarboxylate as the central linker, namely the (E)‐ and (Z)‐forms of N‐[2‐[(3‐amino‐3‐iminopropyl)(15N)aminocarbonyl]‐1‐methylpyrrole‐4‐aminocarbonyl]‐1‐methylpyrrole‐4‐yl],N′‐[2‐[2‐[(3‐amino‐3‐Iminopropyl)aminocarbonyl]‐1‐methylpyrrole‐4‐aminocarbonyl]‐1‐methylpyrrol‐4‐yl]‐2‐butenediamide (18 & 28) are described. A highly convergent synthetic route was adopted for the preparation of the trans‐derivative starting from N‐methyl‐4‐nitro‐2‐trichloroacetylpyrrole and fumaroyl chloride. The most efficient methods of coupling aminopyrrole intermediates with activated carboxylic acid derivatives were utilized and the 15N‐labelled moleties were Incorporated In the later stages of the synthesis. The preparation of the cis‐derivative, starting with maleic anhydride, required a modification of the above strategy due to the nature of products formed upon Initial coupling with aminopyrrole derivatives. 1H‐ and 15N‐NMR were used to fully characterize the final products. The 1H NMR experiment allowed the assignment of an intramolecular hydrogen bond for the cis bis‐netropsin 28.
Synthesis of mycophenolate mofetil‐[14C], RS‐61443‐14C
Authors: Huang Glenn T. , Parnes Howard 
Published: October 2006

AbstractSynthesis of the potent immunosuppressive agent, mycophenolate mofetil (1) labelled with carbon‐14 is described. Methoxyethoxymethyl (MEM) protected mycophenolate norbromide (9) was prepared from unlabelled mycophenolic acid (2) using a modified Hunsdiecker reaction. A three step synthesis furnished the title compound, having a specific activity of 53.8 mCi/mmol, in 49.5% overall yield from K14CN.
Deuteration of acetanilides and other substituted aromatics using [Ir(COD)(Cy3P)(Py)]PF6 as catalyst
Authors: Hesk D. , Das P. R. , Evans B. 
Published: October 2006

AbstractDeuterium exchange labelling using [Ir(COD)(Cy3P)(Py)]PF6 as catalyst and deuterium gas was studied on a number of substituted acetanilides. In most cases products containing deuterium ortho to the anilide group were obtained with a high degree of enrichment. With one exception no evidence for meta, para or anilide methyl labelling was seen. The catalyst was also effective in the ortho deuteration of acetophenone, benzophenone and the β‐lactam containing compound Sch 48461.
The 18F‐labelled alkylating agent 2,2,2‐trifluoroethyl triflate: Synthesis and specific activity
Authors: Johnström Peter , Stone‐Elander Sharon 
Published: October 2006

AbstractA method for synthesizing the alkylating agent 2,2,2‐trifluoroethyl triflate labelled with [18F]fluoride in the two position is presented. Ethyl [2‐18F]‐trifluoroacetate was synthesized by the nucleophilic reaction of [18F]F− with ethyl bromodifluoroacetate in DMSO (45‐60%, 5 min, 80 °C) and subsequently converted to [2‐18F]‐2,2,2‐trifluoroethanol using alane in THF (85‐95%, 2 min, 40 °C). Reaction with triflic anhydride in 2,6‐lutidine produced [2‐18F]‐2,2,2‐trifluoroethyl triflate (70‐80%, 1 min, 0 °C). In all three cases the product was removed from the reaction vessel by heating to distil under a stream of nitrogen. [2‐18F]‐2,2,2‐Trifluoroethyl triflate was used to label 2‐oxoquazepam by N‐alkylation in a toluene: DMF mixture (80‐85%, 20 min, 120 °C). Although no‐carrier‐added [18F]F− was used, considerable unlabelled ethyl trifluoroacetate was produced in the first reaction. Varying the conditions for the fluoro‐debromination reaction did not appreciably improve the relative ratio of labelled to unlabelled ester. The specific activity of the labelled 1,4‐benzodiazepine‐2‐one obtained from 1850 MBq [18F]F− was found to be ≈37 MBq/μmol (1 mCi/μmol).
Synthesis of [3H]DIPPA: A potent irreversible antagonist selective for the κ opioid receptor
Authors: Chang An‐Chih , Trometer Joseph D. , Portoghese Philip S. 
Published: October 2006

Abstract2‐(3,4‐Dichlorophenyl)‐N‐methyl‐N‐[(1S)‐1‐(3‐isothiocyanatophenyl)‐2‐(1‐pyrrolidinyl)ethyl]acetamide (1, DIPPA) has been previously reported to be an opioid receptor affinity label that produces selective and long‐lasting κ opioid receptor antagonism in mice, High specific activity [3H]DIPPA (39.7 Ci/mmol) was prepared by bromination and catalytic tritiation of the amino precursor of DIPPA followed by conversion to the isothiocyanate with thiophosgene.
Synthesis and characterization of 7α‐O‐iodoallyl diprenorphine: A new ligand for potential spect imaging of opioid receptors
Authors: Wang R. F. , Tafani J. A. M. , Bergon M. , Tisnes P. , Coulais Y. , Zajac J. M. , Guiraud R. 
Published: October 2006

AbstractThe preparation and synthesis of [125I]7α‐O‐iodoallyl diprenorphine, a high affinity opioid receptor antagonist, is described using a versatile vinylstannane as prosthetic group for radioiodination at the tertiary alcohol group in the 7α‐side chain. Radioiododestannylation with selective conditions in one step occurs under mild, no‐carrier‐added‐conditions to give the corresponding [125I]7α‐O‐iodoallyl diprenorphine analogue in good radiolabelled yields (70‐90%) with specific radioactivity 80 TBq/mmol (2200 Ci/mmol) and radiochemical purity > 95%. Iodoallyl diprenorphine exhibited in vitro a very high affinity (Ki = 0.4 nM), so that this radioligand could be suitable for imaging opioid receptors in living humans by Single Photon Emission Computed Tomography (SPECT).
Syntheses of isotopically labeled 4‐[1‐(3,5,5,8,8‐pentamethyl‐5,6,7,8‐tetrahydro‐2‐naphthyl)ethenyl]benzoic acid (LGD1069), a potent retinoid x receptor‐selective ligand
Authors: Zhang Lin , Badea Beth Ann , Enyeart Debra , Berger Elaine M. , Mais Dale E. , Boehm Marcus F. 
Published: October 2006

AbstractLGD1069, 4‐[1‐(3,5,5,8,8‐pentamethyl‐5,6,7,8‐tetrahydro‐2‐naphthyl)ethenyl] benzoic acid, is the first retinoid X receptor (RXR) selective retinoid to enter clinical trials for treatment of dermatological diseases and cancer. In order to examine biological properties such as receptor binding, metabolism and bioavailability, [13C]‐, [14C]‐, and [3H]‐labeled LGD1069 is required. Herein, we describe synthetic methods for preparing isotopically labeled homologs of LGD1069 as well as comparative competition binding data for [6,7‐3H]‐LGD1069 and [3H]‐9‐cis retinoic acid with RXR active retinoids. The final radiolabeled products, [6,7‐3H]‐LGD1069 and 3‐[14C]‐LGD1069 have specific activities of 56 Ci/mmol and 49 mCi/mmol, respectively. Radiochemical purities are 99.5% for [6,7‐3H]‐LGD1069 and 99.0% for 3‐[14C]‐LGD1069. The chemical purity is 99.0% for 3‐[13CD3]‐LGD1069. Competition binding studies with known retinoids show similar Kd values when either [6,7‐3H]‐LGD1069 or [3H]‐9‐cis retinoic acid is used as the radioligand.
Enantioselective synthesis of isotopically labelled L‐α‐amino acids preparation of 13C‐, 18O‐and 2H‐labelled L‐serines and L‐threonines
Authors: Karstens W. F. J. , Berger H. J. F. F. , Van Haren E. R. , Lugtenburg J. , Raap J. 
Published: October 2006

Abstract[3‐18O]‐L‐serine, [3‐13C]‐L‐serine, [3‐18O]‐L‐threonine, [3,4‐13C2]‐L‐threonine and [3‐2H]‐L‐threonine are prepared from simple commercially available, isotopically enriched starting materials like H218O, [13C]‐paraformaldehyde, [13C2]‐acetaldehyde and [1‐2H]‐acetaldehyde. The introduction of the side chain is based on the reaction of the anion of the bislactimether of cyclo‐(D‐Val‐Gly) with a suitable reagent. For serine this is isotopically labelled benzylchloromethylether, whereas for threonine labelled acetaldehyde is used in combination with chlorotitaniumtris[diethylamide], introducing both stereocentres in one single step. The isotopomers of serine and threonine are obtained on the gram scale in good yields and high enantiomeric and diasteriomeric excesses. New syntheses for [18O]‐benzylalcohol and isotopically enriched benzylchloromethylether are reported. Following the presented synthetic scheme these amino acids can be labelled at any position or at any combination of positions.
Synthese von 4, 4′ ‐Difluorbenzhydryl‐ [a14C] ‐1‐ Piperazin
Authors: Donnert D. , Schweer K. ‐H. 
Published: October 2006

AbstractThe synthesis of 4, 4′‐Difluorbenzhydryl‐[a14C] ‐1‐piperazin starting with Ba14CO3is described. The identity of the labelled compound was established by comparison with the unlabelled one, synthesized by the same method. The latter was identified with the aid of elementary analysis, mass‐ and infrared spectroscopy.
Neural evolution in the bat-free habitat of Tahiti: partial regression in an anti-predator auditory system
Authors: Fullard James H , Ratcliffe John M , ter Hofstede Hannah 
Published: October 2006

AbstractNoctuid moths endemic to the mountains of Tahiti have evolved in an environment without bats and these insects have lost a defensive behaviour against these predators, the acoustic startle response (ASR). The ASR in noctuid moths is presumed to be activated by a single auditory receptor neuron (A2 cell) and we report that while this cell still exists in endemic species and possesses similar sensitivity thresholds compared to the A2 cell of recently introduced species, it exhibits reduced firing activity to ASR-evoking sounds. This partial neural regression suggests that the evolutionary disappearance of the ASR in these insects is incomplete and that sensoribehavioural integration decays gradually following the removal of stabilizing selective forces.
The Liverwort Marchantia polymorpha Expresses Orthologs of the Fungal Agaricus bisporus Agglutinin Family
Authors: Peumans Willy J. , Fouquaert Elke , Jauneau Alain , Rougé Pierre , Lannoo Nausicaä , Hamada Hiroki , Alvarez Richard , Devreese Bart , Van Damme Els J.M. 
Published: October 2006

Abstract
A lectin different from the previously described mannose-binding agglutinins has been isolated from the liverwort Marchantia polymorpha. Biochemical characterization of the purified lectin combined with the data from earlier transcriptome analyses demonstrated that the novel M. polymorpha agglutinin is not related to any of the known plant lectin families, but closely resembles the Agaricus bisporus-type lectins, which hitherto have been found exclusively in fungi. Immunolocalization studies confirmed that lectin is exclusively associated with plant cells, ruling out the possibility of a fungal origin. Extensive screening of publicly accessible databases confirmed that, apart from fungi, the occurrence of A. bisporus-type lectins is confined to M. polymorpha and the moss Tortula ruralis. Expression of a typical fungal protein in a liverwort and a moss raises the question of the origin of the corresponding genes. Regardless of the evolutionary origin, the presence of a functional A. bisporus lectin ortholog in M. polymorpha provides evidence for the expression of an additional carbohydrate-binding domain in Viridiplantae.
SIZ1 Small Ubiquitin-Like Modifier E3 Ligase Facilitates Basal Thermotolerance in Arabidopsis Independent of Salicylic Acid
Authors: Yoo Chan Yul , Miura Kenji , Jin Jing Bo , Lee Jiyoung , Park Hyeong Cheol , Salt David E. , Yun Dae-Jin , Bressan Ray A. , Hasegawa Paul M. 
Published: October 2006

Abstract
Small ubiquitin-like modifier (SUMO) conjugation/deconjugation to heat shock transcription factors regulates DNA binding of the peptides and activation of heat shock protein gene expression that modulates thermal adaptation in metazoans. SIZ1 is a SUMO E3 ligase that facilitates SUMO conjugation to substrate target proteins (sumoylation) in Arabidopsis (Arabidopsis thaliana). siz1 T-DNA insertional mutations (siz1-2 and siz1-3; Miura et al., 2005) cause basal, but not acquired, thermosensitivity that occurs in conjunction with hyperaccumulation of salicylic acid (SA). NahG encodes a salicylate hydroxylase, and expression in siz1-2 seedlings reduces endogenous SA accumulation to that of wild-type levels and further increases thermosensitivity. High temperature induces SUMO1/2 conjugation to peptides in wild type but to a substantially lesser degree in siz1 mutants. However, heat shock-induced expression of genes, including heat shock proteins, ascorbate peroxidase 1 and 2, is similar in siz1 and wild-type seedlings. Together, these results indicate that SIZ1 and, by inference, sumoylation facilitate basal thermotolerance through processes that are SA independent.
A Pentatricopeptide Repeat Protein Facilitates the trans-Splicing of the Maize Chloroplast rps12 Pre-mRNA
Authors: Schmitz-Linneweber Christian , Williams-Carrier Rosalind E. , Williams-Voelker Pascale M. , Kroeger Tiffany S. , Vichas Athea , Barkan Alice 
Published: October 2006

Abstract
The pentatricopeptide repeat (PPR) is a degenerate 35–amino acid repeat motif that is widely distributed among eukaryotes. Genetic, biochemical, and bioinformatic data suggest that many PPR proteins influence specific posttranscriptional steps in mitochondrial or chloroplast gene expression and that they may typically bind RNA. However, biological functions have been determined for only a few PPR proteins, and with few exceptions, substrate RNAs are unknown. To gain insight into the functions and substrates of the PPR protein family, we characterized the maize (Zea mays) nuclear gene ppr4, which encodes a chloroplast-targeted protein harboring both a PPR tract and an RNA recognition motif. Microarray analysis of RNA that coimmunoprecipitates with PPR4 showed that PPR4 is associated in vivo with the first intron of the plastid rps12 pre-mRNA, a group II intron that is transcribed in segments and spliced in trans. ppr4 mutants were recovered through a reverse-genetic screen and shown to be defective for rps12 trans-splicing. The observations that PPR4 is associated in vivo with rps12-intron 1 and that it is also required for its splicing demonstrate that PPR4 is an rps12 trans-splicing factor. These findings add trans-splicing to the list of RNA-related functions associated with PPR proteins and suggest that plastid group II trans-splicing is performed by different machineries in vascular plants and algae.
A p67Phox-Like Regulator Is Recruited to Control Hyphal Branching in a Fungal–Grass Mutualistic Symbiosis
Authors: Takemoto Daigo , Tanaka Aiko , Scott Barry 
Published: October 2006

Abstract
Key requirements for microbes to initiate and establish mutualistic symbiotic interactions with plants are evasion of potential host defense responses and strict control of microbial growth. Reactive oxygen species (ROS) produced by a specific NADPH oxidase isoform, NoxA, regulate hyphal growth in the mutualistic interaction between the fungal endophyte Epichloë festucae and its grass host Lolium perenne. Unlike mammalian systems, little is known about the fungal NADPH oxidase complex and its response to differentiation signals. We identify an E. festucae p67phox-like regulator, NoxR, dispensable in culture but essential in planta for the symbiotic interaction. Plants infected with a noxR deletion mutant show severe stunting and premature senescence, whereas hyphae in the meristematic tissues show increased branching leading to increased fungal colonization of pseudostem and leaf blade tissue. Inhibition of ROS production or overexpression of noxR recapitulates the hyperbranching phenotype in culture. NoxR interacts in vitro with the small GTP binding protein RacA and requires a functional RacA binding site to complement the noxR mutant and restore the wild-type plant interaction phenotype. These results show that NoxR is a key regulator of NoxA in symbiosis, where it acts together with RacA to spatially regulate ROS production and control hyphal branching and patterning.
Low dose recombinant human growth hormone normalizes bone metabolism and cortical bone density and improves trabecular bone density in growth hormone deficient adults without causing adverse effects
Authors: Amato Giovanni , Izzo Giovanni , La Montagna Giovanni , Bellastella Antonio 
Published: October 2006

SummaryOBJECTIVES Prolonged GH deficiency Induces alterations In bone metabolism and structure. Trials In GH deficient adults (GHDA) employing high dose GH replacement therapy produced conflicting results, and caused several adverse effects. This prompted us to study the effects of rhGH treatment on bone metabolism and structure at lowest doses so far used.DESIGN Nine GHDA (7 males and 2 females, aged 25–34 years) were studied before, after 12 months of rhGH treatment (70 μg/kg/week, divided Into 3 Injections, administered s.c. at 2000 h on Monday, Wednesday and Friday, respectively) and after 12 months off therapy.MEASUREMENTS Serum IGF‐I, IGFBP‐3, bone‐gla‐protein (BOP), procollagen‐III (PIIINP), PTH and vitamin D, and bone mineral density (BMD) at proximal (Prox) and ultradistal (Dist) sites of the radius were measured.RESULTS Before treatment, IGF‐I, IGFBP‐3, BGP and PIIINP levels, as well as both Prox and Dist BMD, were significantly lower than In controls. GH therapy normalized all these parameters, except for the Dist value, which nonetheless Increased. No significant changes In PTH and vitamin D variation were seen. After 12 months off therapy all parameters returned to pretreatment levels.CONCLUSIONS Our results suggest that 12 months of rhGH treatment at the lowest doses so far used normalizes bone metabolism and cortical bone density, and Improves trabecular bone density without causing adverse events.
Effect of fenfluramine on episodic ACTH and cortisol secretion
Authors: Schürmeyer Thomas H. , Brademann Götz , von zur Mühlen Alexander 
Published: October 2006

SummaryOBJECTIVE The central serotoninergic system is known to modulate the activity of the hypothalamic‐pituitary‐adrenal axis, but the effect of fenfluramine, a serotonin reuptake inhibitor, on ACTH and cortisol secretion is not well understood. We have therefore evaluated its effects on the hypothalamic‐pituitary‐adrenal axis in healthy controls.DESIGN Episodic secretion of ACTH and cortisol was Investigated in 6 healthy volunteers under basal conditions and again during treatment with 20 and 60 mg fenfluramine given orally every 8 hours. On all occasions blood samples were obtained at 10‐minute Intervals for 24 hours and the mode of hormone secretion was analysed by three different methods (PULSAR, CLUSTER, DESADE). In addition ACTH and cortisol responses to CRH were tested at the end of the sampling period.RESULTS At the lower dose fenfluramine had no effect on ACTH and cortisol secretion. At the higher dose a significant increase of mean plasma ACTH (+ 85%) and cortisol (+129%) levels as well as of urinary free cortisol secretion (+44%) was observed. Fenfluramine did not modulate the frequency, but increased the amplitudes of ACTH and cortisol secretory episodes. ACTH and cortisol responses to CRH injection remained unchanged. Maximum plasma levels of d‐fenfluramine and d‐nortenfluramine were documented 2–4 hours after the ingestlon of the drug.CONCLUSION Fenfluramine stimulates the activity of the hypothalamic‐pituitary‐adrenal axis at a suprapituitary level by modulating the amplitude of ACTH and cortisol secretory bursts.
Access to stroke care units in Australian public hospitals: facts and temporal progress
Authors: Cadilhac D. A. , Lalor E. E. , Pearce D. C. , Levi C. R. , Donnan G. A. 
Published: October 2006

AbstractBackground: There is level I evidence that management of stroke patients in stroke units (SU) improves outcomes (death and institutionalization) by approximately 20%. In Australia, there is uncertainty as to the proportion of incident cases that have access to SU. Recent national and State‐based policy initiatives to increase access to SU have been taken. However, objective evidence related to SU implementation progress is lacking. The aims of the study were (i) to determine the number of SU in Australian acute public hospitals in 2004, (ii) to describe hospitals according to national SU policy criteria and (iii) to compare results to the 1999 survey to track progress.Methods: The method used in the study was a cross‐sectional, postal survey technique. The participants were clinical representatives considered appropriate to describe stroke care within survey hospitals.Results: The outcome of the study was presence of a SU according to an accepted definition. Response rate was 261/301 (87%). Sixty‐one sites (23%) had either a SU and/or a dedicated stroke team. Fifty sites claimed to have a SU (19%). New South Wales with 23 had the most number of SU. Based on policy criteria, up to 64 sites could have a SU. In 1999, there were 35 public hospitals with a SU.Conclusion: Access to SU in Australian public hospitals remains low compared with other countries (Sweden, 70%). Implementation strategies supported by appropriate health policy to improve access are needed.
Comparison and validation of three measures of quality of life in patients with pulmonary hypertension
Authors: Chua R. , Keogh A. M. , Byth K. , O’Loughlin A. 
Published: October 2006

AbstractBackground: Pulmonary hypertension, when advanced, markedly limits exercise capacity, activities of daily living and quality of life (QoL). No measure of QoL has yet been validated for the assessment of pulmonary hypertension. The aim of the study was to compare the validity of the Minnesota Living with Heart Failure (MLwHF) questionnaire, the Short Form‐36 (SF‐36) questionnaire and the Australian Quality of Life (AQoL) measure for assessing pulmonary hypertension treatment.Methods: Eighty‐three patients were enrolled in three studies of pulmonary hypertension treatment (treprostinil, bosentan and sildenafil). They were assessed at baseline and 3 months with the MLwHF questionnaire. Treprostinil and bosentan groups also had 6 and 12 months’ data. Twenty‐one patients in the sildenafil trial completed concurrently, the SF‐36 and AQoL measures at baseline and 3 months. QoL scores were correlated with the 6‐min walk test distance, New York Heart Association functional class and right heart catheter‐derived haemodynamic parameters of the disease for all matching time points and for changes in scores and clinical measurements over time.Results: The MLwHF and SF‐36 scores correlated well with the 6‐min walk test distance and New York Heart Association functional class, but did not correlate with haemodynamic measurements. MLwHF and SF‐36 scores also correlated with the rate of change of the 6‐min walk test distance and New York Heart Association functional class over time.Conclusion: The MLwHF questionnaire and SF‐36 are useful tools for the assessment of QoL in pulmonary hypertension and may be useful in the ongoing evaluation of QoL in the treatment and study of pulmonary hypertension.