bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of tritium labeled renin inhibitor ditekiren
Authors: Hsi Richard S. P. , Stolle Wayne T. , Bundy Gordon L.
Published: October 2006

In the search for a radioactive form of the peptidomimetic renin inhibitor, ditekiren, with a metabolically suitable radiolabel for conducting drug disposition studies, we prepared [3H]ditekiren with tritium labels in the N‐methyl‐histidine moiety and in the leu‐val alcohol transition‐state insert. [His‐3H]ditekiren was obtained by first introducing two iodine substituents into the N‐methyl‐histidine moiety of the parent drug, followed by catalytic hydrodehalogenation with tritium gas. Administration of this labeled drug to monkeys, however, resulted in prolonged retention of radioactivity in the test animals, even though little or no tritiated water was detected in urine. This suggested in vivo production of a labeled fragment from the drug, e.g., N‐methyl‐[3H]histidine, which became incorporated into the endogenous amino acid pool. These results, together with similar earlier findings after administration of [3H]ditekiren labeled in the proline moiety of the drug, led us to synthesize [3H]ditekiren labeled in the “unnatural” leu‐val alcohol (LVA) portion of the molecule. [LVA‐3H]ditekiren was obtained by first oxidizing the parent drug to produce an LVA‐keto analog, which was then reduced with sodium borotritide to give a mixture of tritium labeled ditekiren and its LVA‐epimer. The two epimeric labeled materials were separated and purified by means of preparative high performance liquid chromatography (HPLC). The tritium label in [LVA‐3H]ditekiren was found to be metabolically suitable for conducting drug disposition studies, with no liability for tritiated water production or prolonged retention of radioactivity in tissues of test animals.
Synthesis of Z‐ and E‐[2,3‐2H2] and [2,3‐3H2]‐1,1‐dichloro‐2,3‐ diphenylcyclopropane (2H‐ and 3H‐analog II and its trans isomer)
Authors: Day Billy W. , Jonnalagadda Sastry S.
Published: October 2006

2H and 3H labeled Z‐ and E‐1,1‐dichloro‐2,3‐diphenylcyclopropane (1 and 2) were synthesized starting from NaB2H4 and NaB3H4 reduction of benzil. The resulting glycols were transformed to the 1,2‐labeled Z‐ and E‐stilbenes by thermolysis of their cyclic thionocarbonates in trimethylphosphite. The stilbenes were reacted with phase transfer‐generated dichlorocarbene to form the title compounds. The dideuterio isomers were separated by fractional crystallization in yields of 60 and 48%. Each was greater than 99 % geometrically and 98 % isotopically pure. The ditritio isomers were separated by C‐18 JPLC. The radiochemical yields, on a molar basis using benzil as the limiting reagent, were 42 % and 23 %, each with specific activity of 88.5 mCi/mmol and radiochemical purity of > 95%.
Synthesis of N‐tert‐butyl‐α‐(4‐[18F]fluorophenyl)‐nitrone ([18F]FPBN) for in vivo detection of free radicals
Authors: Bormans G. , Kilbourn M. R.
Published: October 2006

We have synthesized the fluorine‐18 labeled derivative of N‐tert‐butyl‐α‐phenylnitrone (PBN), a free radical spin trapping agent widely used with electron spin resonance (ESR). N‐tert‐Butyl‐α‐(4‐[18F]fluorophenyl)‐nitrone ([18F]FPBN) could be prepared with low radiochemical yield (3% decay corrected) by the direct aromatic nucleophilic substitution of N‐tert‐butyl‐α‐(4‐nitrophenyl)nitrone with [18F]fluoride. An alternate two step synthesis route consisted of the nucleophilic [18F]fluoride substitution of 4‐N, N, N‐trimethylammoniumbenzaldehyde triflate to yield 4‐[18F]fluorobenzaldehyde, which was distilled into a vial containing N‐tert‐butyl‐hydroxylamine in 2N NaOH. 4‐[18F]Fluorobenzaldehyde readily reacted with the hydroxylamine to form [18F]FPBN. [18F]FPBN was obtained in overall decay corrected yields of 24% in a total synthesis time < 45 min. and was suitable for further applications in in vivo studies of free radicals.
Radiosynthesis of a chloroacetanilide herbicide ([phenyl‐4‐3H] acetochlor) and a dichloroacetamide safener for herbicides ([2, 2‐dimethyl‐3H]R‐29148)
Authors: Latli Bachir , Casida John E.
Published: October 2006

2‐Chloro‐N‐(ethoxymethyl)‐N‐(2‐ethyl‐6‐methylphenyl)acetamide (the chloroacetanilide herbicide acetochlor) and 3‐(dichloroacetyl)‐ 2,2,5‐trimethyl‐1,3‐oxazolidine (the dichloroacetamide safener R‐ 29148) are required at high specific activity for studies on their metabolism and mode of action. [phenyl‐4‐3H]Acetochlor was obtained at 22 Ci/mmol in 71% yield by reductive dehalogenation of iodoacetochlor with tritium gas in ethanol in the presence of palladium on carbon and triethylamine. [2,2‐dimethyl‐3H]R‐29148 was prepared at 15 Ci/mmol by treating acetone and 1‐amino‐2‐propanol in pentane with two equivalents of NaOH in tritiated water (i.e. hydroxide ion‐catalyzed enolization of acetone) followed by dichloroacetyl chloride.
Synthesis and E.I.M.S. fragmentation analysis of [1,3‐15N2] xanthine and [1,3‐15N2] caffeine
Authors: Kenani A. , Bernier J‐L. , Henichart J‐P.
Published: October 2006

HPLC and mass spectrometry can be used to isolate and identify all metabolites of caffeine in plasma of patients. The synthesis of [1,3‐15N2] xanthine and [1,3‐ 15N2] caffeine are of interest in the elucidation of mass spectrometry fragmentation pathways and the unambiguous determination of metabolites, especially uric acid which exists as a natural constituent of human plasma.
Esters of 6‐(4′‐fluorobenzylamino)‐β‐ carboline‐3‐carboxylic acid as potential benzodiazepine imaging agents for P.E.T.
Authors: Elder S. T. , Mach R. H. , Nowak P. A. , Moroney D. A. , Rao A. V. , Ehrenkaufer R. L. E.
Published: October 2006

As potential P.E.T. imaging agents for the benzodiazepine receptor, two fluorine‐ 18 labeled analogues of the β‐carbolines were prepared via N‐ alkylation of the corresponding desbenzyl amine precursors with [18F]fluorobenzyl iodide.
Deuteriodediazoniation: A general method for the replacement of a diazonium group by deuterium
Authors: Wassmundt Frederick W. , Kiesman William F.
Published: October 2006

Aromatic amino groups are replaced with deuterium via a diazonium salt intermediate. Dimethylformamide‐d7 is the deuterium donor in this mild replacement method that yields aromatic‐d1 products in high isotopic purity. The presence of methyl groups lowers the isotopic purity of the products.
Synthesis of 2β‐carbomethoxy‐3β‐(4‐[76Br]bromophenyl)tropane ([76Br]β‐CBT), a pet tracer for in vivo imaging of the dopamine uptake sites
Authors: Loc'h Christian , Müller Lars , Ottaviani Michèle , Halldin Christer , Farde Lars , Mazière Bernard
Published: October 2006

2β‐carbomethoxy‐3β‐(4‐[76Br]bromophenyl)tropane ([76Br]β‐CBT) was prepared either by electrophilic substitution from the tributyl‐stannyl derivative and peracetic acid as oxidant or by nucleophilic substitution from the iodo analogue (β‐CIT) and a Cu+ assisted bromodeiodination exchange. After purification by solid phase extraction and reverse phase HPLC, the chemical and radiochemical purities of [76Br]β‐CBT were > 98% and the specific radioactivity was 20 GBq/μmol. Using the two labelling techniques, the radiochemical yields were 80% and 60%, respectively. From the deshalogeno compound and different oxidizing conditions, the radiolabelling yields were < 5%. In vitro competition and saturation pharmacological studies showed that [76Br]β‐CBT mainly labelled the dopamine transporter and bound to a single population of sites in striatal membranes (Bmax = 6.5 pmol/mg protein) with an apparent dissociation constant of 2.8 nM. Biodistribution and autoradiography studies of the title compound in rats showed that 3 h post injection, the highest concentration in the brain was found in the striata (2.5% ID/g). 24 h post injection, the striatum to cerebellum radioactive concentration ratio was still 17.
Synthesis of 14C‐labelled 6‐hydroxy‐5,7‐dimethyl‐2‐(methylamino)‐4‐(3‐pyridylmethyl)benzothiazole dihydrochloride (14C‐E3040 dihydrochloride)
Authors: Hibi Shigeki , Numata Hirotoshi , Okamoto Yasushi , Takenaka Osamu , Mishima Mannen
Published: October 2006

14C‐Labelled 6‐hydroxy‐5,7‐dimethyl‐2‐(methylamino)‐4‐(3‐pyridylmethyl)‐benzothiazole dihydrochloride (14C‐E3040 dihydrochloride), required for a study of the phrmacokinetic profile of E3040, a novel dual inhibitor of 5‐lipoxygenase and thromboxane A2 synthetase, was synthesized in one step using [2‐14C]‐1‐methyl‐2‐thiourea as the labelled starting material. 14C‐E3040 dihydrochloride with a specific activity of 58.0mCi/mmol was prepared in 60% chemical yield(based on thiourea 2).
Synthesis and biodistribution of 14C‐radiolabelled hypocrellin B
Authors: Liu Jixiang , Miller Gerald G. , Huang Liren , Diwu Zhenjun , Lown J. William , Brown Kevin , Moore Ronald B. , Tulip John , McPhee Malcolm S.
Published: October 2006

Our research group is currently exploring the use of hypocrellins as potential photosensitizers for photodynamic therapy (PDT). The purpose of this study is to investigate the synthesis and biodistribution of 14C‐labelled Hypocrellin B. Radiolabelled hypocrellin‐B (HB) with the 14C atom incorporated in either or both the 4‐ and 13‐methoxy groups was synthesized with a specific activity of 2.11 mCi per mmol. The purified, 14C‐HB, prototype photodynamic therapy photosensitizer was used to determine the kinetics of uptake in EMT6/Ed cells in monolayer culture, and the kinetics of tumor and tissue distribution in Balb/c mice bearing the EMT6/Ed tumor.
Synthesis of selectively 13C‐labelled benzoic acid for nuclear magnetic resonance spectroscopic measurement of glycine conjugation activity
Authors: Akira Kazuki , Hasegawa Hiroshi , Baba Shigeo
Published: October 2006

The synthesis of [4‐13C]benzoic acid (BA) labelled in a single protonated carbon, for use as a probe to measure glycine conjugation activity by nuclear magnetic resonance (NMR) spectroscopy, has been reported. The labelled compound was prepared by a seven‐step synthetic scheme on a relatively small scale using [2‐13C]acetone as the source of label in overall yield of 16 %. The usefulness of [4‐13C]BA was demonstrated by the NMR spectroscopic monitoring of urinary excretion of [4‐13C]hippuric acid in the rat administered with the labelled BA.
Comparison of two synthetic methods to obtain [18F] N‐(2‐aminoethyl)‐5‐fluoropyridine‐2‐carboxamide, a potential MAO‐B imaging tracer for PET
Authors: Beer H.‐F. , Haeberli M. , Ametamey S. , Schubiger P. A.
Published: October 2006

The compound Ro 19‐6327, N‐(2‐aminoethyl)‐5‐chloropyridine‐2‐carboxamide, is known to inhibit reversibly and site specifically the enzyme monoamine oxidase B (MAO‐B). The 123I‐labelled iodo‐analogue N‐(2‐aminoethyl)‐5‐iodopyridine‐2‐carboxamide (Ro 43‐0463) was investigated successfully in human volunteers by means of SPET (Single Photon Emission Tomography). We developed therefore the synthesis and radiolabelling of the corresponding fluoro‐analogue N‐(2‐aminoethyl)‐5‐fluoropyridine‐2‐carboxamide with 18F in order to carry out PET (Positron Emission Tomography) investigations of MAO‐B related neuropsychiatric diseases. For this purpose two synthetic approaches leading to the electrophilic and the nucleophilic methods of 18F radiolabelling were undertaken. The nucleophilic approach appeared to be superior when factors such as precursor synthesis, beam time, specific activity and radiochemical purity of the product are considered.
Preparation of [11C]‐thymidine and [11C]‐2′‐arabino‐2′‐fluoro‐β‐5‐methyl‐uridine (FMAU) using a hollow fiber membrane bioreactor system
Authors: Hughes Jeffrey A. , Hartman Neil G. , Jay Michael
Published: October 2006

A series of hollow fiber membranes containing immobilized enzymes were prepared and used in the synthesis of 11C‐labelled nucleosides. 11C‐Formaldehyde was produced in an alcohol oxidase/catalase bioreactor and circulated through a thymidylate synthase bioreactor with an appropriate substrate to produce the corresponding 11C‐nucleotide. These labelled nucleotides were subsequently dephosphorylated in an alkaline phosphatase bioreactor. The bioreactor approach was amenable to hot‐cell conditions and yielded 11C‐products in higher yield and shorter synthesis times than conventional chemical approaches.
Radiosynthesen biologisch aktiver verbindungen. II Triforine (cela W 524) markiert mit tritum und 14C
Authors: Stiasni Michael , Ost Walter
Published: October 2006

Ausgehend von Piperazin‐3H (V) wird tritiwmarkiertes Triforine (N, N′‐Bis‐[ 1‐formamido‐2, 2, 2‐trichloröthy1] ‐piperazin ‐ 3H) mit 89 % Ausbeute und einer spezifischen Aktivität von 149 mCi/mNol dargestellt. Bei. der 14C‐Markieruna wird Paraldehyd ‐14C (U) zu Chloral ‐1, 2‐14C ungesetzt und als Chloral ‐ 1, 2‐ 14 C‐formamid isoliert. Dieses wird chloriert und mit piperazin kondensiert. Triforine‐14C entsteht in 25 %‐iger Ausbeute mit einer spezifischem Aktivität von 22 mCi/mMol.
Variable‐oriented and person‐oriented perspectives of analysis: The example of alcohol consumption in adolescence
Authors: von Eye Alexander , Anne Bogat G. , Rhodes Jean E.
Published: October 2006

This article presents person‐oriented and variable‐oriented approaches to data analysis. To illustrate these two approaches and the types of information they provide the researcher, data from 3558 control group youth from the National Cross‐Site Evaluation of High Risk Youth Programs were analysed. The relationship, over time, between parent attitudes and gender as it relates to youth alcohol consumption were examined. Data were analysed and compared using a variable‐oriented approach (repeated measures ANOVA) and a person‐oriented approach (Configural Frequency Analysis). Data analysis demonstrated that variable‐ and person‐oriented approaches provide the researcher with different information that can be complementary. The ANOVA identified an overall trend that accounted for little variance; the CFA explained why this was the case by identifying groups of respondents whose behaviour was different from the overall trend. The implications of these results and the use of both types of approaches are discussed.
An Automated High-Throughput Screening Enzyme Linked Immunosorbent Assay for Johne's Disease Antibodies in Bovine Serum
Authors: Wu John T.Y. , Wong Lester S.Y. , Bowlby Evelyn E.
Published: October 2006

Amanual Mycobacterium avium subspecies paratuberculosis antibody enzyme linked immunosorbent assay (ELISA) (IDEXX Inc.) was fully automated using an automation workstation system (AWS). The IDEXX commercial kit is used to screen for exposure to the Johne's disease (JD) bacterium in cattle on a herd basis. Due to the large number of sera involved in this type of surveillance project, there is a need to increase the cost effectiveness and decrease the turn around time. The purpose of the work was to develop an automated ELISA (a-ELISA) for JD antibodies screening and examine the productivity advantages, quality assured performance characteristics, the laboratory information management (LIM) work, and the multitasking provisions under this format.

The AWS was assembled using a modular approach design. The high-throughput screening configuration consisted of a Beckman Coulter hybrid Biomek FX liquid-handling system integrated with a Molecular Devices Spectramax microplate reader, a Biotek ELx405 microplate washer, a Kendro Cytomat 6000 hotel, and an Axis PTZ Network camera. The integrated system function was programmed with an IBM computer using the SAMI software. This setup was housed in a Class 2 Biosafety Cabinet. This fully automated system provided flexibility to accommodate the multistep requirements of the immunoassay procedure. Complexity of the working steps was kept to a minimum by using one unique operation program. The complete robotic workstation with its peripheral equipment was simple to operate, robust, and easily maintained. These characteristics enabled the elimination of forced downtime due to human and/or machine failure. A 5 to 10 fold improvement in cost, test capacity, and productivity was achieved. With this system, one diagnostician is able to carry out over 1000 antibody screening tests a day. Based on the automated nature of the test, there is ample walk away time between the ELISA tests, enabling the technologist to multitask–performing other important duties such as sample receiving and preparation, test validation, result interpretation, information dissemination, and other related LIM work.

The performance characteristics–such as repeatability, reproducibility, optimal cutoff values, identity score, test sensitivity, and specificity were evaluated. These test validation results were based on data accumulated in an 8-year proficiency testing with the US National Veterinary Services Laboratory. Our laboratory test has received certification from the United States Department of Agriculture to perform serologic testing for JD since 1998. In 2000–2001, this test scope was accredited by the Standard Council of Canada. In 2004, this a-ELISA was validated according to the requirements of the ISO/IEC 17025 standard.
A high-resolution reconstruction of Storglaciären mass balance back to 1780/81 using tree-ring data and circulation indices
Authors: Linderholm Hans W. , Jansson Peter , Chen Deliang
Published: October 2006

Storglaciären in northernmost Sweden has the world's longest ongoing continuous mass-balance record, starting in 1946. To extend this mass-balance record, we have reconstructed summer (bS) and winter (bW) mass balances separately back to the mass balance year 1780/81 with annual resolution. We used tree-ring data for bS and a set of circulation indices, based on the sea-level pressure, for bW. Both proxies have correlation coefficients with respective mass balance components of ca. 0.7. The reconstructed net balance (bN) of Storglaciären was well correlated to the observations during 1946–1980 (r = 0.8, p < 0.05). Our reconstruction agrees well with previously obtained results of northern Sweden glacier variability, where the predominantly positive bN years between 1890 and 1910 correspond to the well documented post-Little Ice Age advance of Storglaciären. Furthermore, the results suggest that bS, as a function of summer temperatures, is more important than bW in determining the bN, which is contrary to glaciers in the maritime parts of western Scandinavia. In general, bN has been negative over the last 220 yr, suggesting a predomination of continental conditions over northern Sweden. However, the influence of bW increased in the late twentieth century, indicating a shift to a more oceanic climate regime.
The Role of Adult Attachment Styles in Psychopathology and Psychotherapy Outcomes
Authors: Shorey Hal S. , Snyder C. R.
Published: October 2006

Attachment theory provides a model for understanding how the attachment styles formed in infancy systematically affect subsequent psychological functioning across the life span. Attachment styles provide the cognitive schemas, or working models, through which individuals perceive and relate to their worlds. In turn, these schemas predispose the development of psychopathologies and influence outcomes when people undergo psychotherapy. After reviewing recent empirical findings, the authors conclude that an understanding of attachment theory facilitates the conceptualization of clients' problems and the selection of appropriate interventions. Accordingly, attachment styles should be assessed as a standard part of treatment planning. Furthermore, the authors propose that attachment styles should be assessed as individual difference variables in psychotherapy outcome research because adult attachment styles dictate how people perceive and respond to their environments and, therefore, how clients respond differentially to various treatments.
Forsaking Optimism
Authors: Carroll Patrick , Sweeny Kate , Shepperd James A.
Published: October 2006

Although subjective optimism is generally regarded as adaptive, people show a sharp decline in optimism when they anticipate self-relevant feedback in the near future. The authors discuss moderators of the shift in future outlooks as well as reasons for the shift. The authors propose that the shift can reflect a response to new information or an attempt to brace for undesired outcomes. Both explanations represent a response to an adaptive need to prepare for uncertain states of the world. Finally, the authors discuss unanswered questions and directions for future research.
Comparative estimation of the reproduction number for pandemic influenza from daily case notification data
Authors: Chowell Gerardo , Nishiura Hiroshi , Bettencourt Luís M.A
Published: October 2006

The reproduction number,, defined as the average number of secondary cases generated by a primary case, is a crucial quantity for identifying the intensity of interventions required to control an epidemic. Current estimates of the reproduction number for seasonal influenza show wide variation and, in particular, uncertainty bounds forfor the pandemic strain from 1918 to 1919 have been obtained only in a few recent studies and are yet to be fully clarified. Here, we estimateusing daily case notifications during the autumn wave of the influenza pandemic (Spanish flu) in the city of San Francisco, California, from 1918 to 1919. In order to elucidate the effects from adopting different estimation approaches, four different methods are used: estimation ofusing the early exponential-growth rate (Method 1), a simple susceptible–exposed–infectious–recovered (SEIR) model (Method 2), a more complex SEIR-type model that accounts for asymptomatic and hospitalized cases (Method 3), and a stochastic susceptible–infectious–removed (SIR) with Bayesian estimation (Method 4) that determines the effective reproduction numberat a given timet. The first three methods fit the initial exponential-growth phase of the epidemic, which was explicitly determined by the goodness-of-fit test. Moreover, Method 3 was also fitted to the whole epidemic curve. Whereas the values ofobtained using the first three methods based on the initial growth phase were estimated to be 2.98 (95% confidence interval (CI): 2.73, 3.25), 2.38 (2.16, 2.60) and 2.20 (1.55, 2.84), the third method with the entire epidemic curve yielded a value of 3.53 (3.45, 3.62). This larger value could be an overestimate since the goodness-of-fit to the initial exponential phase worsened when we fitted the model to the entire epidemic curve, and because the model is established as an autonomous system without time-varying assumptions. These estimates were shown to be robust to parameter uncertainties, but the theoretical exponential-growth approximation (Method 1) shows wide uncertainty. Method 4 provided a maximum-likelihood effective reproduction number 2.10 (1.21, 2.95) using the first 17 epidemic days, which is consistent with estimates obtained from the other methods and an estimate of 2.36 (2.07, 2.65) for the entire autumn wave. We conclude that the reproduction number for pandemic influenza (Spanish flu) at the city level can be robustly assessed to lie in the range of 2.0–3.0, in broad agreement with previous estimates using distinct data.
Embolism Formation during Freezing in the Wood ofPicea abies
Authors: Mayr Stefan , Cochard Hervé , Améglio Thierry , Kikuta Silvia B.
Published: October 2006

Freeze-thaw events can cause embolism in plant xylem. According to classical theory, gas bubbles are formed during freezing and expand during thawing. Conifers have proved to be very resistant to freeze-thaw induced embolism, because bubbles in tracheids are small and redissolve during thawing. In contrast, increasing embolism rates upon consecutive freeze-thaw events were observed that cannot be explained by the classical mechanism. In this study, embolism formation during freeze-thaw events was analyzed via ultrasonic and Cryo-scanning electron microscope techniques. Twigs of Picea abies L. Karst. were subjected to up to 120 freeze-thaw cycles during which ultrasonic acoustic emissions, xylem temperature, and diameter variations were registered. In addition, the extent and cross-sectional pattern of embolism were analyzed with staining experiments and Cryo-scanning electron microscope observations. Embolism increased with the number of freeze-thaw events in twigs previously dehydrated to a water potential of −2.8 MPa. In these twigs, acoustic emissions were registered, while saturated twigs showed low, and totally dehydrated twigs showed no, acoustic activity. Acoustic emissions were detected only during the freezing process. This means that embolism was formed during freezing, which is in contradiction to the classical theory of freeze-thaw induced embolism. The clustered pattern of embolized tracheids in cross sections indicates that air spread from a dysfunctional tracheid to adjacent functional ones. We hypothesize that the low water potential of the growing ice front led to a decrease of the potential in nearby tracheids. This may result in freezing-induced air seeding.
Common Plantain. A Collection of Expressed Sequence Tags from Vascular Tissue and a Simple and Efficient Transformation Method
Authors: Pommerrenig Benjamin , Barth Inga , Niedermeier Matthias , Kopp Sina , Schmid Jürg , Dwyer Rex A. , McNair Racella J. , Klebl Franz , Sauer Norbert
Published: October 2006

The vascular tissue of higher plants consists of specialized cells that differ from all other cells with respect to their shape and size, their organellar composition, their extracellular matrix, the type of their plasmodesmata, and their physiological functions. Intact and pure vascular tissue can be isolated easily and rapidly from leaf blades of common plantain (Plantago major), a plant that has been used repeatedly for molecular studies of phloem transport. Here, we present a transcriptome analysis based on 5,900 expressed sequence tags (ESTs) and 3,247 independent mRNAs from the Plantago vasculature. The vascular specificity of these ESTs was confirmed by the identification of well-known phloem or xylem marker genes. Moreover, reverse transcription-polymerase chain reaction, macroarray, and northern analyses revealed genes and metabolic pathways that had previously not been described to be vascular specific. Moreover, common plantain transformation was established and used to confirm the vascular specificity of a Plantago promoter-β-glucuronidase construct in transgenic Plantago plants. Eventually, the applicability and usefulness of the obtained data were also demonstrated for other plant species. Reporter gene constructs generated with promoters from Arabidopsis (Arabidopsis thaliana) homologs of newly identified Plantago vascular ESTs revealed vascular specificity of these genes in Arabidopsis as well. The presented vascular ESTs and the newly developed transformation system represent an important tool for future studies of functional genomics in the common plantain vasculature.
Insulin‐like growth factor‐I and IGF binding protein‐3 remain high after GnRH analogue therapy in girls with central precocious puberty
Authors: Kanety Hannah , Karasik Avraham , Pariente Clara , Kauschansky Arieh
Published: October 2006

OBJECTIVE IGF‐I rises in normal adolescence and in central precocious puberty (CPP), secondary to a rise in sex steroids and GH. The aim of this study was to examine changes in serum IGF‐I and its major binding protein IGFBP‐3 after pharmacological arrest of puberty.

PATIENTS AND MEASUREMENTS Ten girls diagnosed for CPP were evaluated before and during the first 3 months of GnRH analogue (GnRHa) therapy aimed at Suppression of the gonadal axis. Serum IGF‐I was measured by immunoradiometric assay (IRMA) and IGFBP‐3 by both IRMA and Western ligand blotting (WLB).

RESULTS Serum IGF‐I was markedly higher in patients with CPP as compared with age matched controls (48.8 ± 6.5 vs 23.1 ± 4.9 nmol/l, P < 0.01). While GnRHa therapy caused serum oestradiol levels to return to pre‐pubertal levels in all 10 patients, serum IGF‐I levels decreased only minimally after 1, 2 or 3 months of therapy (43.2 ± 5.6, 42.3 ± 6.4 and 44.1 ± 7.2 nmol/l respectively). Serum IGFBP‐3 levels as determined using IRMA were also higher in CPP compared with age matched controls (4.70 ± 0.37 vs 3.71 ± 0.42mg/l, P < 0.01). These differences were also evident when measured by WLB. GnRHa therapy caused a small and insignificant decrease in serum IGFBP‐3 levels after 1, 2 or 3 months of therapy (4.57 ± 0.33, 4.48 ± 0.4 and 4.42 ± 0.3 mg/l respectively).

CONCLUSIONS The lack of suppression of both IGF‐I and IGFBP‐3, despite therapy which halts puberty and slows growth velocity, suggests that steroids may be involved In the Induction of changes in the GH/IGF‐I axis but not in their subsequent maintenance.
Clinical features of adrenal insufficiency in patients with acquired immunodeficiency syndrome
Authors: Piédrola Gonzalo , Casado Jose L. , López Elena , Moreno Ana , Perez‐Elías Maria J. , García‐Robles Rafael
Published: October 2006

OBJECTIVE Adrenal insufficiency (Al) is a well known complication of AIDS. However, the clinical and biochemical features of Al in HIV infected patients have not been extensively studied.

DESIGN A restrospective clinical study.

PATIENTS We reviewed clinical records of 74 AIDS patients with clinical and/or biochemical indications of Al who underwent Synacthen testing in order to determine adrenocortical function during a 5‐year period.

MEASUREMENTS AI was diagnosed when Cortisol levels failed to rise above 496 nmol/l at any time during the test. Cortisol was measured by RIA.

RESULTS Sixteen patients (22%) were diagnosed with Al. Most were young males and all of them had a known risk factor, principally I.v. drug users. The main complaint was fatigue. Hyponatraemia or hyperkalaemia were uncommon. All of them were severely immuno‐suppressed, with AIDS‐defining conditions from at least 6 months before the diagnosis of Al, and had been diagnosed with at least one disease that has been reported to produce Al in AIDS patients. Survival was poor. Thirteen of these patients (81%) died within 6 months. Basal cortisol levels were lower than 275 nmol/l in 75% of patients with Al but in only 2% of the group of 58 patients who had normal adrenal responses to Synacthen.

CONCLUSIONS Adrenal insufficiency features in AIDS patients with advanced disease, without specific findings and with a history of previous opportunistic diseases. Basal cortisol values at 0830 h lower than 275 nmol/l are highly suggestive of adrenal insufficiency in patients with AIDS.
AtCAT6, a sink‐tissue‐localized transporter for essential amino acids in Arabidopsis
Authors: Hammes Ulrich Z. , Nielsen Erik , Honaas Loren A. , Taylor Christopher G. , Schachtman Daniel P.
Published: October 2006

Amino acids represent the major form of reduced nitrogen that is transported in plants. Amino acid transporters in plants often show tissue‐specific expression patterns and are used by plants to transport these metabolites from source to sink during development and under changing environmental conditions. We identified one amino acid transporter, AtCAT6, which is expressed in sink tissues such as lateral root primordia, flowers and seeds. Additionally AtCAT6 was induced during infestation of roots by the plant‐parasitic root‐knot nematode, Meloidogyne incognita. Quantitative reverse‐transcriptase PCR revealed nematode inducibility throughout the duration of nematode infestation and in nematode‐induced feeding sites. Promoter analyses confirmed expression in endogenous sink tissues and nematode‐induced feeding sites. In Xenopus oocytes, AtCAT6 mediated electrogenic transport of proteinogenic as well as non‐proteinogenic amino acids with moderate affinity. AtCAT6 transported large, neutral and cationic amino acids in preference to other amino acids. Knockout mutants of this transporter failed to grow on medium containing l‐glutamine as the sole nitrogen source. Our data suggest that AtCAT6 plays a role in supplying amino acids to sink tissues of plants and nematode‐induced feeding structures.
In vivo demonstration of enhanced probiotic effect of co‐immobilized Lactobacillus acidophilus and Bifidobacterium bifidum
Authors: KUSHAL RUCHI , ANAND SANJEEV K , CHANDER HARISH
Published: October 2006

The present study was undertaken to evaluate the effectiveness of co‐immobilization as an efficient method for delivering high numbers of viable probiotic cultures to the host for an enhanced probiotic effect, using in vivo mice models. The co‐immobilized culture of Lactobacillus acidophilus and Bifidobacterium bifidum was fed to eight groups of conventional mice. A greater persistence of probiotic cultures was noticed in the intestinal contents of the groups fed on co‐immobilized cells. Further, the supplementation of diet with co‐immobilized culture also resulted in maximum lowering of faecal coliforms and the enzymatic activity as compared to the prestudy level.
Effect of syncytiotrophoblast microvillous membrane treatment on gene expression in human umbilical vein endothelial cells
Authors: Hoegh AM , Tannetta D , Sargent I , Borup R , Nielsen FC , Redman C , Sørensen S , Hviid TVF
Published: October 2006

Objective  Syncytiotrophoblast membrane fragments (STBM) exist in the peripheral circulation in pregnant women and it has been shown that the level of circulating STBM is significantly increased with pre‐eclampsia compared with uncomplicated pregnancies. STBM could be one of the factors which directly causes the endothelial cell dysfunction of pre‐eclampsia. This study investigates the effect of STBM on endothelial cell gene expression.

Design  Human umbilical vein endothelial cells were cultured in the presence and absence of STBM. At specified time points, total RNA was purified from the cultures and analysed on microarrays.

Setting  A laboratory investigation using placentas obtained from a hospital delivery ward.

Sample  Placentas from nine healthy women were obtained. STBM vesicles were isolated from the placentas and umbilical vein endothelial cell cultures were established from the umbilical cords.

Methods  Gene expression was screened by Affymetrix GeneChips and confirmed with real‐time polymerase chain reaction or enzyme‐linked immunosorbent assay.

Main outcome measures  Fold changes in gene expression levels between treated and control cultures were calculated from the microarray results.

Results  Overall, the results do not show any great changes in gene expression in endothelial cells after STBM treatment (28 genes changed two‐fold or more out of approximately 10 000 genes examined by microarray). In general, the changes observed are consistent with inhibition of proliferation of endothelial cells by exposure to STBM. The unfolded protein response in particular may be involved.

Conclusions  STBM may influence endothelial cell function during pregnancy but STBM alone cannot account for the entire range of endothelial dysfunctions observed in pre‐eclampsia.
A long‐term study of women with normal colposcopy after referral with low‐grade cytological abnormalities
Authors: Smith MCG , Keech SEJ , Perryman K , Soutter WP
Published: October 2006

Background  About 50 000 women are referred annually to colposcopy in England because of a low‐grade smear. About 35% of these women have no colposcopic abnormality but are followed up in the colposcopy clinic because of uncertainty about the risk of significant pathology.

Objective  This study determined the 5‐year rate of disease when initial colposcopy was normal and smear was non‐dyskaryotic.

Design  Retrospective study.

Setting  Colposcopy clinic of an inner city postgraduate teaching hospital.

Population  Two thousand one hundred and fifty seven women referred between January 1990 and December 2001 with mild dyskaryosis (Low Grade Squamous Intraepithelial Lesion [LSIL]) or borderline nuclear changes (Abnormal Squamous Changes of Uncertain Significance [ASCUS]).

Methods  Information was obtained from the colposcopy clinic database and Open‐Exeter. Time plots of the disease‐free rates were generated using the Kaplan–Meier method, and statistical comparisons were performed using Cox regression.

Main outcome measures  Cumulative rates of cytological and histological abnormalities.

Results  High‐grade or invasive disease was diagnosed histologically in 12.8% of 805 women referred with borderline nuclear changes and in 35.8% of 1352 referred with mild dyskaryosis. Among 620 women with normal colposcopy and a negative or borderline repeat smear, high‐grade disease was found after 5 years of follow up in 1.3% of women originally referred with a borderline smear and in 8.5% referred because of mild dyskaryosis.

Conclusion  Women referred to colposcopy with borderline nuclear changes or mild dyskaryosis whose colposcopy findings are normal and whose repeat smear in the clinic is non‐dyskaryotic may be discharged for routine 3‐yearly screening in the community because the risk of high‐grade disease in the next 5 years is small.
Human Immunodeficiency Virus Type 1 Gag Polyprotein Modulates Its Own Translation
Authors: Anderson Emma C. , Lever Andrew M. L.
Published: October 2006

The full-length viral RNA of human immunodeficiency virus type 1 (HIV-1) functions both as the mRNA for the viral structural proteins Gag and Gag/Pol and as the genomic RNA packaged within viral particles. The packaging signal which Gag recognizes to initiate genome encapsidation is in the 5′ untranslated region (UTR) of the HIV-1 RNA, which is also the location of translation initiation complex formation. Hence, it is likely that there is competition between the translation and packaging processes. We studied the ability of Gag to regulate translation of its own mRNA. Gag had a bimodal effect on translation from the HIV-1 5′ UTR, stimulating translation at low concentrations and inhibiting translation at high concentrations in vitro and in vivo. The inhibition was dependent upon the ability of Gag to bind the packaging signal through its nucleocapsid domain. The stimulatory activity was shown to depend on the matrix domain of Gag. These results suggest that Gag controls the equilibrium between translation and packaging, ensuring production of enough molecules of Gag to make viral particles before encapsidating its genome.
Swimming stress in DN 14-3-3 mice triggers maladaptive cardiac remodeling: role of p38 MAPK
Authors: Watanabe Ken-ichi , Ma Meilei , Hirabayashi Ken-ichi , Gurusamy Narasimman , Veeraveedu Punniyakoti T. , Prakash Paras , Zhang Shaosong , Muslin Anthony J. , Kodama Makoto , Aizawa Yoshifusa
Published: October 2006

It is generally believed that a mechanical signal initiates a cascade of biological events leading to coordinated cardiac remodeling. 14-3-3 family members are dimeric phosphoserine-binding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. To evaluate the molecular mechanism underlying swimming stress-induced cardiac remodeling, we examined the role of 14-3-3 protein and MAPK pathway by pharmacological and genetic means using transgenic mice with cardiac-specific expression of dominant-negative (DN) mutants of 14-3-3 (DN 14-3-3/TG) and p38α/β MAPK (DNp38α and DNp38β) mice. p38 MAPK activation was earlier, more marked, and longer in the myocardium of the TG group compared with that of the nontransgenic (NTG) group after swimming stress, whereas JNK activation was detected on day 5 and decreased afterward. In contrast, ERK1/2 was not activated after swimming stress in either group. Cardiomyocyte apoptosis, cardiac hypertrophy, and fibrosis were greatly increased in the TG group compared with those in the NTG group. Moreover, we found a significant correlation between p38 MAPK activation and apoptosis in the TG group. Furthermore, DN 14-3-3 hearts showed enhanced atrial natriuretic peptide expression. In contrast, DNp38α and DNp38β mice exhibited reduced mortality and increased resistance to cardiac remodeling after 28 days of swimming stress compared with TG and NTG mice. Besides, treatment with a p38 MAPK inhibitor, FR-167653, resulted in regression of cardiac hypertrophy and fibrosis and improvement in the survival rate in the TG group. These results indicate for the first time that 14-3-3 protein along with p38 MAPK plays a crucial role in left ventricular remodeling associated with swimming stress.
The Significance of Contextual Factors in African American Students’ Transfer of Learning
Authors: Serpell Zewelanji N. , Boykin A. Wade , Madhere Serge , Nasim Aashir
Published: October 2006

This study sought to address the lack of experimental research examining the influence of contextual factors on African American students’ learning. A total of 162 low-income African American and White fourth graders were randomly assigned to ethnically homogeneous, communally structured groups of three to work on a motion acceleration task using either computer simulation or physical tools, or to a control group that did not participate in the learning activities. A 3 (condition) × 2 (ethnicity) MANOVA was computed with initial learning and transfer as dependent variables. Results indicate African American and White students performed equally well on the test of initial learning, with both groups scoring significantly higher than the control group. However, African Americans’ transfer outcomes were better than those of their White counterparts. Regarding tools, work with physical apparatus yielded better transfer outcomes than work with computer simulation. Implications for creating optimal learning contexts for African American students are discussed.
Culture and Antiracisms in Adult Education: An Exploration of the Contributions of Arts-Based Learning
Authors: Clover Darlene E.
Published: October 2006

Increasingly, practices of collective arts-based learning are being used by adult educators and community organizations as creative and participatory ways to respond to contemporary social or environmental issues. Investigating the potential contributions of arts-based learning to cross-cultural and antiracisms adult education was the aim of this qualitative comparative study in Ontario and British Columbia. Through the lens of antiracisms theories and from data obtained through open-ended interviews with project participants and artist-educators in three diverse arts projects, this article highlights some of the characteristics that make arts-based learning a culturally appropriate and effective, imaginative tool. But it also draws attention to the risks involved in creating public art and tacking difficult issues such as racism in contemporary Canadian society.
Faculty Lived Experiences in the Online Environment
Authors: Conceição Simone C. O.
Published: October 2006

This phenomenological study investigated the meaning of the online teaching experience of college faculty when there was an absence of physical presence. Findings show that the online experience brings new dimensions to the teaching practice when there is an absence of physical presence: (a) The length and depth of engagement during the delivery of the course differs from face-to-face teaching and (b) the experience is rewarding in new ways. Practical implications are suggested for adult education related to teaching improvement and instructional design.
Winning Coverage
Authors: Barakso Maryann , Schaffner Brian F.
Published: October 2006

Contemporary feminist scholars and activists often criticize the women's movement for focusing on a narrow agenda that does not represent the true needs of American women.Yet a review of the agendas of women's movement organizations reveals a broad concern for many of the issues that they are criticized for ignoring. What explains this disconnect? The authors argue that the news media plays a crucial role in shaping the perceptions of social movements by choosing to cover some agendas and not others.Analyzing coverage of women's movement organizations in television and print news media, the authors find that reporters have exercised a great deal of discretion over which women's movement issues they have chosen to report on during the past three decades. In particular, this has led to overrepresentation of the abortion issue in news coverage of women's movement organizations and an underrepresentation of issues that women believe should be more of a priority for the movement. The authors’ findings underscore the importance of the news media not only for bringing attention to social movements, but also for how they portray the issue agendas of these movements.
Taking the “Low Road” with Subliminal AdvertisementsA Study Testing the Effect of Precognitive Prime “RATS” in a 2000 Presidential Advertisement
Authors: Stewart Patrick A. , Schubert James N.
Published: October 2006

Despite extensive research successfully using subliminals to affect individual attitudes, public understanding and public policy response reflect a lack of awareness of their effectiveness.This article attempts to redress this by presenting findings concerning the effectiveness of one class of subliminal stimuli, precognitive primes. It then considers the effect of the controversial “RATS” subliminal political advertisement. Here the term “RATS” appeared on screen for one frame, that is, one-thirtieth of a second, as part of an attack ad by the Republican National Committee criticizing presidential candidate Al Gore's prescription drug plan. An experiment carried out on Election Day 2000 presented the advertisement with or without the RATS frame, as well as a parallel Medicare ad by the Gore campaign, to subjects. Findings suggest that while evaluations and behavioral intentions were not significantly affected, attitudes toward Medicare, the political parties, and Al Gore were significantly affected by the subliminal stimulus.The experiment was small in scale, so the findings are far from definitive. But they suggest a need for further research on the topic.
Transcriptional regulation of the cannabinoid receptor type 1 gene in T cells by cannabinoids
Authors: Börner Christine , Höllt Volker , Sebald Walter , Kraus Jürgen
Published: October 2006

Effects of cannabinoids (CBs) are mediated by two types of receptors, CB1 and CB2. In this report, we investigated whether CBs regulate gene expression of their cognate receptors in T cells and studied underlying mechanisms in CD4+ Jurkat T cells. Transcription of the CB1 gene was strongly induced in response to Δ9-tetrahydroannabinol (THC), whereas the CB2 gene was not regulated. The induction of CB1 gene expression is mediated by CB2 receptors only, as demonstrated by using the CB1 and CB2 agonists R(+)-methanandamide and JWH 015, respectively, and combinations of THC plus CB1- and CB2-specific antagonists. After activation of CB2 receptors, the transcription factor STAT5 is phosphorylated. STAT5 then transactivates IL-4. Induction of IL-4 mRNA as well as IL-4 protein release from the cells are necessary for the following induction of the CB1 gene. This was demonstrated by using decoy oligonucleotides against STAT5, which blocked IL-4 and CB1 mRNA induction, and by using the IL-4 receptor antagonist IL-4 [R121D, Y124D], which blocked the up-regulation of CB1 gene transcription. Transactivation of the CB1 gene in response to IL-4 is then mediated by the transcription factor STAT6, as shown by using decoy oligonucleotides against STAT6. An increase in CB1-mediated phosphorylation of MAPK in cells prestimulated with CB2-specific agonists suggests up-regulation of functional CB1 receptor proteins. In summary, up-regulation of CB1 in T lymphocytes in response to CBs themselves may facilitate or enhance the various immunomodulatory effects related to CBs.