bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Bases of Estrogen-Induced Pituitary Tumorigenesis
Authors: Strecker Tracy E , Spady Thomas J , Schaffer Beverly S , Gould Karen A , Kaufman Amy E , Shen Fangchen , McLaughlin Mac T , Pennington Karen L , Meza Jane L , Shull James D
Published: February 2005

Estrogens stimulate proliferation and enhance survival of the prolactin (PRL)-producing lactotroph of the anterior pituitary gland and induce development of PRL-producing pituitary tumors in certain inbred rat strains but not others. The goal of this study was to elucidate the genetic bases of estrogen-induced pituitary tumorigenesis in reciprocal intercrosses between the genetically related ACI and Copenhagen (COP) rat strains. Following 12 weeks of treatment with the synthetic estrogen diethylstilbestrol (DES), pituitary mass, an accurate surrogate marker of absolute lactotroph number, was increased 10.6-fold in ACI rats and 4.5-fold in COP rats. Composite interval mapping analyses of the phenotypically defined F2 progeny from the reciprocal crosses identified six quantitative trait loci (QTL) that determine the pituitary growth response to DES. These loci reside on chromosome 6 [Estrogen-induced pituitary tumor (Ept)1], chromosome 3 (Ept2 and Ept6), chromosome 10 (Ept9), and chromosome 1 (Ept10 and Ept13). Together, these six Ept loci and one additional suggestive locus on chromosome 4 account for an estimated 40% of the phenotypic variance exhibited by the combined F2 population, while 34% of the phenotypic variance was estimated to result from environmental factors. These data indicate that DES-induced pituitary mass behaves as a quantitative trait and provide information that will facilitate identification of genes that determine the tumorigenic response of the pituitary gland to estrogens.
The Rad1-Rad10 Complex Promotes the Production of Gross Chromosomal Rearrangements From Spontaneous DNA Damage in Saccharomyces cerevisiae
Authors: Hwang Ji-Young , Smith Stephanie , Myung Kyungjae
Published: February 2005

Gross chromosomal rearrangements (GCRs) have been observed in many cancers. Previously, we have demonstrated many mechanisms for suppression of GCR formation in yeast. However, pathways that promote the formation of GCRs are not as well understood. Here, we present evidence that the Rad1-Rad10 endonuclease, which plays an important role in nucleotide excision and recombination repairs, has a novel role to produce GCRs. A mutation of either the RAD1 or the RAD10 gene reduced GCR rates in many GCR mutator strains. The inactivation of Rad1 or Rad10 in GCR mutator strains also slightly enhanced methyl methanesulfonate sensitivity. Although the GCRs induced by treatment with DNA-damaging agents were not reduced by rad1 or rad10 mutations, the translocation- and deletion-type GCRs created by a single double-strand break are mostly replaced by de novo telomere-addition-type GCR. Results presented here suggest that Rad1-Rad10 functions at different stages of GCR formation and that there is an alternative pathway for the GCR formation that is independent of Rad1-Rad10.
Autosomal Genes of Autosomal/X-Linked Duplicated Gene Pairs and Germ-Line Proliferation in Caenorhabditis elegans
Authors: Maciejowski John , Ahn James Hyungsoo , Cipriani Patricia Giselle , Killian Darrell J , Chaudhary Aisha L , Lee Ji Inn , Voutev Roumen , Johnsen Robert C , Baillie David L , Gunsalus Kristin C , Fitch David H A , Hubbard E Jane Albert
Published: February 2005

We report molecular genetic studies of three genes involved in early germ-line proliferation in Caenorhabditis elegans that lend unexpected insight into a germ-line/soma functional separation of autosomal/X-linked duplicated gene pairs. In a genetic screen for germ-line proliferation-defective mutants, we identified mutations in rpl-11.1 (L11 protein of the large ribosomal subunit), pab-1 [a poly(A)-binding protein], and glp-3/eft-3 (an elongation factor 1-α homolog). All three are members of autosome/X gene pairs. Consistent with a germ-line-restricted function of rpl-11.1 and pab-1, mutations in these genes extend life span and cause gigantism. We further examined the RNAi phenotypes of the three sets of rpl genes (rpl-11, rpl-24, and rpl-25) and found that for the two rpl genes with autosomal/X-linked pairs (rpl-11 and rpl-25), zygotic germ-line function is carried by the autosomal copy. Available RNAi results for highly conserved autosomal/X-linked gene pairs suggest that other duplicated genes may follow a similar trend. The three rpl and the pab-1/2 duplications predate the divergence between C. elegans and C. briggsae, while the eft-3/4 duplication appears to have occurred in the lineage to C. elegans after it diverged from C. briggsae. The duplicated C. briggsae orthologs of the three C. elegans autosomal/X-linked gene pairs also display functional differences between paralogs. We present hypotheses for evolutionary mechanisms that may underlie germ-line/soma subfunctionalization of duplicated genes, taking into account the role of X chromosome silencing in the germ line and analogous mammalian phenomena.
Effects of Alcohol Intake During Pregnancy on Docosahexaenoic Acid and Arachidonic Acid in Umbilical Cord Vessels of Black Women
Authors: Beblo Skadi , Stark Ken D. , Murthy Mahadev , Janisse James , Rockett Helaine , Whitty Janice E. , Buda-Abela Michelle , Martier Susan S. , Sokol Robert J. , Hannigan John H. , Salem Norman
Published: February 2005

Objective. Alcohol influences the intake and metabolism of several nutrients including long-chain polyunsaturated fatty acids (LC-PUFAs). The LC-PUFAs docosahexaenoic acid (DHA) and arachidonic acid (AA) are particularly crucial for intrauterine growth and brain development. We hypothesized that alcohol consumption adversely affects LC-PUFA levels in pregnant women and their newborn infants.

Methods. Pregnant black women (N = 208) presenting at a core city antenatal clinic were screened and recruited. Shortly before delivery, maternal plasma was collected. After delivery, umbilical arteries and veins were dissected from the cords, total lipids were extracted from the vessel tissues and maternal plasma, and fatty acid levels were assayed by gas chromatography. For statistical analysis, subjects were categorized according to absolute alcohol intake per day (AAD) and absolute alcohol intake per drinking day (AADD) around the time of conception, with smoking and other potential confounders included in the analyses.

Results. Significant differences in fatty acid composition of total lipid extracts were detected in umbilical cord vessels among the AADD groups: abstainers (AADD = 0), moderate drinkers (AADD < 130 g), and heavy drinkers (AADD ≥ 130 g). DHA and AA content in the arterial umbilical vessel wall was ∼14% and ∼10% higher in the moderate (n = 127) and heavy (n = 32) alcohol groups, respectively, than in abstainers (n = 49). A small, nonsignificant increase (∼3%) was seen in the umbilical vein for AA but not for DHA. Alcohol intake was positively correlated to both DHA and AA concentrations in the arterial vessel wall but to neither in the venous wall nor maternal plasma. Maternal plasma DHA was positively correlated with both umbilical arteries and vein DHA, but there were no significant correlations for AA between maternal plasma and either umbilical vessel.

Conclusions. Our findings indicate that alcohol intake during pregnancy is associated with altered DHA and AA status in fetal tissues. Although differences may be due to either metabolism and/or distribution, it is most likely a result of a direct influence of alcohol on fetal metabolism.
Obesity and Renal Transplant Outcome: A Report of the North American Pediatric Renal Transplant Cooperative Study
Authors: Hanevold Coral D. , Ho Ping-Leung , Talley Lynya , Mitsnefes Mark M.
Published: February 2005

Objective. Obesity is increasing in the end-stage renal disease population. Studies that have evaluated the effect of obesity on transplant outcomes in adults have yielded varying results. This issue has received little attention in the pediatric population.

Methods. We performed a retrospective study of the effect of obesity on pediatric renal transplant outcomes using the North American Pediatric Renal Transplant Cooperative Study database. Registry data from 1987 through 2002 on 6658 children aged 2 to 17 years were analyzed. Obesity was defined by a BMI >95th percentile for age.

Results. Overall, 9.7% were obese with an increase noted in recent years (12.4% after 1995 vs 8% before 1995). Obese children were significantly younger and shorter and had been on dialysis for a longer time than nonobese children. There was no significant difference in the overall patient and allograft survival between the 2 groups. However, obese children aged 6 to 12 years had higher risk for death than nonobese patients (adjusted relative risk: 3.65 for living donor; adjusted relative risk: 2.94 for cadaver), and death was more likely as a result of cardiopulmonary disease (27% in obese vs 17% in nonobese). Overall, graft loss as a result of thrombosis was more common in obese as compared with nonobese (19% vs 10%).

Conclusions. Obesity is an increasing problem in children who present for transplantation and may have an adverse effect on allograft and patient survival.
School Bullying and Suicidal Risk in Korean Middle School Students
Authors: Kim Young Shin , Koh Yun-Joo , Leventhal Bennett
Published: February 2005

Objective. Being a victim or a perpetrator of school bullying, the most common type of school violence, has been frequently associated with a broad spectrum of behavioral, emotional, and social problems. In a Korean middle school community sample, this study specifically investigated the prevalence of suicidal ideations and behaviors in victims, perpetrators, and victim-perpetrators of school bullying and compared them with a group of students who were in the same schools and were not involved with bullying.

Methods. In a cross-sectional study, 1718 seventh- and eighth-grade students in 2 middle schools participated in the study in October 2000. Students completed demographic information, Korean Peer Nomination Inventory, and Korean Youth Self-Report.

Results. Compared with the students who were not involved with school bullying, victim-perpetrators reported more suicidal/self-injurious behaviors and suicidal ideation in the previous 6 months (odds ratio [OR]: 1.9 and 1.9, respectively). In female students, all 3 school bullying groups had increased suicidal ideation for the previous 2 weeks (OR: 2.8, 2.0, and 2.8, respectively) but not in male students (OR: 0.9, 1.1, and 1.3, respectively).

Conclusions. Students who were involved in school bullying, especially victim-perpetrators and female students, had significantly higher risks for suicide ideation and suicidal behavior when compared with individuals who were not involved in school bullying. In addition to attempting to decrease bullying in a community, students who are involved in school bullying should be the targets for suicide monitoring and prevention programs.
Neuropsychological Functioning and Viral Load in Stable Antiretroviral Therapy-Experienced HIV-Infected Children
Authors: Jeremy Rita J. , Kim Soyeon , Nozyce Molly , Nachman Sharon , McIntosh Kenneth , Pelton Stephen I. , Yogev Ram , Wiznia Andrew , Johnson George M. , Krogstad Paul , Stanley Kenneth ,   for the Pediatric AIDS Clinical Trials Group (PACTG) 338 & 377 Study Teams
Published: February 2005

Objective. Neuropsychological functioning and its correlation with viral load were investigated for previously treated HIV-infected children who underwent a change in treatment regimen.

Methods. Thirteen age-appropriate measures of cognitive, neurologic, and behavioral functioning were administered to 489 HIV-infected children who were aged 4 months to 17 years and had been treated previously for at least 16 weeks with antiretroviral therapy. These clinically and immunologically stable children were randomized onto 1 of 7 drug treatment combinations, 6 of which included a protease inhibitor (PI), and evaluated prospectively for 48 weeks with respect to changes in neuropsychological performance and viral load.

Results. Neuropsychological functioning was significantly poorer at baseline for the HIV-infected children as compared with established norms for their age. Children with higher viral load had poorer cognitive, both-hands fine-motor, and neurologic signs at baseline, but single-hand fine-motor and behavioral functioning were not correlated with viral load. After 48 weeks of treatment with PI-containing combination therapy, there was significant improvement in only the vocabulary score. Neuropsychological changes did not differ among the 6 PI-containing combination regimens. At week 48, even children with a viral load response below the level of detection (RNA ≤400 copies/mL) still showed poorer neuropsychological functioning compared with established norms.

Conclusion. Poor neuropsychological functioning was seen for HIV-infected children and was worse for children with higher viral loads. Only 1 measure of neuropsychological functioning showed improvement after treatment with PI-containing combination therapy, and the extent of that improvement was relatively minor. Treatment strategies for children with HIV disease need to be reevaluated so that they consider restoration of neuropsychological functioning in addition to lowering the viral load.
The Internet and Psychoactive Substance Use Among Innovative Drug Users
Authors: Boyer Edward W. , Shannon Michael , Hibberd Patricia L.
Published: February 2005

Objective. The Internet contains an extraordinary amount of information on the recreational use of psychoactive substances. We investigated the effect of the Internet on the drug-use knowledge, attitudes, and behaviors of adolescents.

Methods. Cross-sectional survey of adolescents being managed for substance abuse.

Results. Of 12 patients (9 male, 3 female) who had used the Internet to learn about psychoactive substances, 100% reported that Internet-based information had affected the ways in which they had used psychoactive substances. Of the 12 respondents, 8 described adopting behaviors intended to minimize the risks associated with psychoactive substance use. Respondents also reported changes in the use of a wide variety of illicit substances as well as over-the-counter and prescription pharmaceuticals. Examiners assessed whether quotations demonstrated that respondents’ knowledge, attitudes, and behaviors toward psychoactive substance use were affected by Internet information. Despite the subjective nature of the research question, there was a highly significant agreement between coders.

Conclusions. Web-based data on psychoactive substances seem to influence a broad range of drug-use behaviors in adolescents. Information on the ways that the Internet is being used by this vulnerable population should be considered in the design of Web sites to prevent the initiation and use of psychoactive substances.
Compliance With National Immunization Guidelines for Children Younger Than 2 Years, 1996-1999
Authors: Mell Loren K. , Ogren David S. , Davis Robert L. , Mullooly John P. , Black Steven B. , Shinefield Henry R. , Zangwill Kenneth M. , Ward Joel I. , Marcy S. Michael , Chen Robert T. ,   for the Centers for Disease Control and Prevention Vaccine Safety Datalink Project
Published: February 2005

Objectives. To evaluate compliance with national immunization guidelines among a large cohort of children cared for at health maintenance organizations (HMOs) and to examine effects on immunization status.

Methods. A cohort study of 176134 children born between January 1, 1994, and December 31, 1997, and monitored from birth to the second birthday was performed. Subjects belonged to the Vaccine Safety Datalink Project, a study of children enrolled in 1 of 4 HMOs. Children were continuously enrolled in a HMO for the first 2 years of life. Prevailing recommendations regarding optimal ages of immunization and intervals between doses were applied to define appropriate immunization timing and immunization status. Noncompliance was defined as having a missing or late immunization or an immunization error. Immunization errors included invalid immunizations (too early to be acceptable), extra immunizations (superfluous immunizations or make-up immunizations for invalid immunizations), and missed opportunities resulting in late or missing immunizations.

Results. Although 75.4% of children in these HMOs were up to date for all immunizations at 2 years, only 35.6% of children were fully compliant with recommended immunization practices. Less than 8% of children received all immunizations in accordance with strict interpretation of recommended guidelines. Fifty-one percent of children had at least 1 immunization error by age 2 years; 29.7% had a missed opportunity with subsequent late or missing immunization, 20.4% had an invalid immunization, and 11.6% had an extra immunization. Common reasons for noncompliance included missed opportunities for the fourth Haemophilus influenzae type b vaccine (14.6%), invalid fourth diphtheria-tetanus-pertussis/acellular pertussis immunizations (11.0%), and superfluous polio immunizations (9.8%).

Conclusions. Approximately 35.6% of children were compliant with prevailing childhood immunization recommendations from 1996 to 1999. Efforts to improve compliance with guidelines are recommended, to optimize childhood infectious disease prevention.
Breastfeeding and the Use of Human Milk
Authors:   Section on Breastfeeding
Published: February 2005

This Policy Statement was revised. See https://doi.org/10.1542/peds.2022-057988.

Considerable advances have occurred in recent years in the scientific knowledge of the benefits of breastfeeding, the mechanisms underlying these benefits, and in the clinical management of breastfeeding. This policy statement on breastfeeding replaces the 1997 policy statement of the American Academy of Pediatrics and reflects this newer knowledge and the supporting publications. The benefits of breastfeeding for the infant, the mother, and the community are summarized, and recommendations to guide the pediatrician and other health care professionals in assisting mothers in the initiation and maintenance of breastfeeding for healthy term infants and high-risk infants are presented. The policy statement delineates various ways in which pediatricians can promote, protect, and support breastfeeding not only in their individual practices but also in the hospital, medical school, community, and nation.
Neonatology Research for the 21st Century: Executive Summary of the National Institute of Child Health and Human Development–American Academy of Pediatrics Workshop. Part II: Training Issues
Authors: Ariagno Ronald L. , Marter Linda J. Van , Higgins Rosemary , Raju Tonse N.K.
Published: February 2005

This is the second part of the executive summary based on the presentations and discussions at a workshop on research in neonatology sponsored by the National Institute of Child Health and Human Development and the American Academy of Pediatrics held in January 2004. In this article, neonatology fellowship training requirements and workforce issues are addressed, and the reasons for the shortage of physician-scientists, particularly of the underrepresented minority ethnic groups, are highlighted. Full-length articles from the presented topics are yet to be published.
Internetworking of factors affecting successive searches over multiple episodes
Authors: Lin Shin‐jeng
Published: February 2005

Successive information searches are fairly common. To enhance the understanding of the behavior, this study attempted to improve both the descriptive and explanatory power of the Multiple Information Seeking Episodes (MISE) model, a conceptual model characterizing factors affecting successive searches. It empirically observed how the key factors in the information seeking process in the MISE model evolve over multiple search sessions and explained how those factors are affected by other factors associated with searchers, search activity, search context, systems, information attainment, and information–use activities. The validated and enriched MISE model can be extended to serve the basis for future studies in other complex searches process such as multi‐tasking and collaborative searches, and can also help identify problems that users face and thus derive requirements for system support.
Orthogonal PbS Nanowire Arrays and Networks and Their Raman Scattering Behavior
Authors: Ge Jian‐Ping , Wang Jin , Zhang Hao‐Xu , Wang Xun , Peng Qing , Li Ya‐Dong
Published: February 2005

Three‐dimensional, orthogonal lead sulfide (PbS) nanowire arrays and networks have been prepared by using a simple, atmospheric pressure chemical vapor deposition (APCVD) method. These uniform nanowires (average diameter 30 nm) grow epitaxially from the surface of the initial PbS crystal seeds and form orthogonal arrays and networks in space. The growth mechanism has been explored, and the process was classified as homogeneous, epitaxial growth in the 〈200〉 directions. Furthermore, Raman spectra of PbS nanowires are reported here, and their characteristic Raman peak (190 cm−1, no shoulder) could be used as a unique probe for the study of PbS nanomaterials.
Alkylchlorotins Grafted to Cross‐Linked Polystyrene Beads by a (CH2)n Spacer (n=4, 6, 11): Selective, Clean and Recyclable Catalysts for Transesterification Reactions
Authors: Camacho‐Camacho Carlos , Biesemans Monique , Van Poeck Manu , Mercier Frédéric A. G. , Willem Rudolph , Darriet‐Jambert Karine , Jousseaume Bernard , Toupance Thierry , Schneider Uwe , Gerigk Ursula
Published: February 2005

Insoluble polystyrene grafted compounds of the type (PH)(1−t){P(CH2)nSnBupCl3−p}t, (PH)(1−t){P(CH2)nSnBuO}t and (PH)(1−t)[{P(CH2)nSnBuCl}2O]t/2, in which (PH) is a cross‐linked polystyrene; n=4, 6, and 11; p=0 and 1; and t the degree of functionalisation, were synthesised from Amberlite XE‐305, a polystyrene cross‐linked with divinylbenzene. The compounds were characterised by using elemental analysis, and IR, Raman, solid‐state 117Sn NMR, and 1H and 119Sn high‐resolution MAS NMR spectroscopy. The influence of the spacer length and the tin functionality on the catalytic activity of these compounds, as well as their recycling ability, was assessed in the transesterification reaction of ethyl acetate with various alcohols. These studies showed significant differences in the activity of the catalysts interpreted in terms of changes in the mobility of the catalytic centres. Some of the supported catalysts could be recycled at least seven times without noticeable loss of activity. The residual tin content in the reaction products was found to be as low as 3 ppm.
Bullvalene Trisepoxide and Its Stereospecific Rearrangement to 2,8,12‐Trioxahexacyclo[8.3.0.03,904,605,1307,11]tridecane: Two New C3‐Symmetrical Oligocycles with Propeller Chirality
Authors: Liang Shelue , Lee Chi‐Hung , Kozhushkov Sergei I. , Yufit Dmitrii S. , Howard Judith A. K. , Meindl Kathrin , Rühl Stephan , Yamamoto Chiyo , Okamoto Yoshio , Schreiner Peter R. , Rinderspacher B. Christopher , de Meijere Armin
Published: February 2005

Epoxidation of bullvalene (1) with a neutralized solution of Oxone gave racemic trisepoxide rac‐6 in 93 % isolated yield. Its structure was examined by X‐ray crystallography. The two enantiomers of 6 were separated by preparative HPLC and exhibited specific rotations of [α]${{{25\hfill \atop {\rm D}\hfill}}}$=+160, [α]${{{25\hfill \atop 365\hfill}}}$= +567 (c=0.946, CHCl3) for the firstly eluted and [α]${{{25\hfill \atop {\rm D}\hfill}}}$=−157, [α]${{{25\hfill \atop 365\hfill}}}$=−554 (c=0.986, CHCl3) for the secondly eluted enantiomer of 6. The geometry of (+)‐6 and the absolute configuration of (−)‐6 were determined by X‐ray crystal structure analysis and anomalous diffraction, respectively. According to this, (−)‐6 possesses (3R,5S,7S,9R,11R,13S)‐ and (+)‐6 has (3S,5R,7R,9S,11S,13R)‐configuration. Upon treatment with BF3⋅Et2O at −78 °C, trisepoxide rac‐6 rearranges with retention of the skeletal three‐membered carbocycle to give the cage trisether rac‐8, as proved by X‐ray crystal structure analysis, in virtually quantitative yield. Enantiomers of rac‐8 were separated by preparative HPLC and exhibited specific rotations of [α]${{{25\hfill \atop {\rm D}\hfill}}}$=+49, [α]${{{25\hfill \atop 365\hfill}}}$=+170 (c=1.01, CHCl3) (firstly eluting) and [α]${{{25\hfill \atop {\rm D}\hfill}}}$=−46, [α]${{{25\hfill \atop 365\hfill}}}$=−160 (c=1.02, CHCl3) (secondly eluting enantiomer). The absolute configuration of (−)‐8 was determined by anomalous diffraction to be (1R,3R,7R,9R,11R,13R). DFT computations at the TD‐B3 LYP/6‐31+G(d,p)//B3 LYP/6‐31+G(d) level of theory for (3R,5S,7S,9R,11R,13S)‐6 and (1R,3R,7R,9R,11R,13R)‐8 predicted specific rotations of −206.7 and −83.4, respectively. Acid‐catalyzed isomerization of the enantiomerically pure (+)‐6 proceeded without racemization to give exclusively (−)‐8, and (−)‐6 provided only (+)‐8. Thus, this isomerization occurs with ring opening of the three CO bonds in the epoxide moieties in the α‐position relative to the three‐membered carbocycle rather than in the β‐position.
Cascade Alkenyl Amination/Heck Reaction Promoted by a Bifunctional Palladium Catalyst: A Novel One‐Pot Synthesis of Indoles from o‐Haloanilines and Alkenyl Halides
Authors: Barluenga José , Fernández M. Alejandro , Aznar Fernando , Valdés Carlos
Published: February 2005

A novel approach for the synthesis of the important indole ring is described. Indoles are obtained from o‐bromoanilines and alkenyl halides in a Pd‐catalyzed cascade process that involves an alkenyl amination followed by an intramolecular Heck reaction. The overall process represents the first example of the participation of alkenyl amination reactions in Pd‐catalyzed cascade reactions. Initially, the relative reactivity of aryl and alkenyl bromides and chlorides towards Pd‐catalyzed amination was investigated. Competition experiments were carried out in the presence of primary and secondary amines, and these revealed the reactivity order alkenyl bromides > aryl bromides > alkenyl chlorides > aryl chlorides, as well as very high chemoselectivity; the more reactive halide was always favored. Thereafter, optimized reaction conditions for the sequential alkenyl amination/Heck cyclization to give indoles were investigated with the model reaction of o‐bromoaniline with α‐bromostyrene. An extensive screening of ligands, bases, and reaction conditions revealed that the [Pd2(dba)3]/DavePhos, NaOtBu, toluene combination at 100 °C were the optimized reaction conditions to carry out the cascade process (dba= dibenzylideneacetone, DavePhos=2‐dicyclohexylphosphino‐2′‐N,N‐dimethylaminobiphenyl). The reaction proceeds with aryl, alkyl, and functionalized substitutents in both starting reactants. The cyclization was also studied with N‐substituted o‐bromoanilines (which would give rise to N‐substituted indoles); however, in this case, indole formation occurred only with 1‐substituted‐2‐bromoalkenes. Finally, the application of this methodology to o‐chloroanilines required further optimization. Although the catalyst based on DavePhos failed to promote the cascade process, a catalytic combination based on [Pd2(dba)3]/X‐Phos promoted the formation of the indole ring also from the less reactive chloroanilines.
Composition of the volatile oils of Phlomis lanceolata Boiss. & Hohen., Phlomis anisodonta Boiss. and Phlomis bruguieri Desf. from Iran
Authors: Sarkhail Parisa , Amin Gholamreza , Surmaghi Mohammad Hossein Salehi , Shafiee Abbas
Published: February 2005

The composition of hydrodistilled essential oils of three species of Phlomis (Lamiaceae), P. lanceolata, P. anisodonta and P. bruguieri, were investigated by GC and GC–MS, and 31, 28 and 21 compounds, representing 94.1%, 96.0% and 96.8%, respectively, of the total oils, were identified. In all three samples, sesquiterpenes were the main components. In P. lanceolata oil the main components were germacrene D (47.0%), (E)‐β‐farnesene (10.5%), α‐pinene (8.7%), germacrene B (8.0%), bicyclogermacrene (5.9%); in P. anisodonta, germacrene D (65.0%) and β‐caryophyllene (11.0%); and in P. bruguieri, germacrene D (60.5%), γ‐elemene (16.5%), germacrene B (7.1%) and bicyclogermacrene (4.1%). Copyright © 2005 John Wiley & Sons, Ltd.
Making company directors liable: a comparative analysis of wrongful trading in the United Kingdom and insolvent trading in Australia
Authors: Keay Andrew , Murray Michael
Published: February 2005

The separate legal entity doctrine in corporate law means that directors are not generally liable for their company's liabilities. However, there have been actions taken by governments and courts to make directors liable in certain cases. This article examines and compares legislative provisions in the United Kingdom and Australia to make directors liable for the debts of their companies. These provisions, namely section 214 of the UK's Insolvency Act 1986 (wrongful trading) and section 588G of the Australian Corporations Act 2001 (insolvent trading), had the same starting point, but now differ substantially, even though, arguably, they retain very similar objectives. The article investigates: the reasons for these differences; the criteria on which each of the provisions focus; and the ramifications for the different approaches. It also endeavours to evaluate the strengths and weaknesses of the respective approaches adopted in each country. Copyright © 2005 John Wiley & Sons, Ltd.
Novel indication for cancer therapy: Chk1 inhibition sensitizes tumor cells to antimitotics
Authors: Xiao Zhan , Xue John , Semizarov Dimitri , Sowin Thomas J. , Rosenberg Saul H. , Zhang Haiying
Published: February 2005

Paclitaxel (Taxol) is the most‐prescribed anti‐mitotic agent for a variety of advanced metastatic cancers. It induces mitotic arrest leading to apoptosis through microtubule stabilization. Chk1 is the major cell‐cycle checkpoint kinase mediating S‐ and G2‐arrests in response to various DNA‐damages. Chk1 inhibitor is anticipated and has been demonstrated to potentiate the cytotoxicity of DNA‐damaging agents through abrogation of cell‐cycle checkpoints. Paclitaxel does not, however, induce Chk1 activation, and Chk1 has not been shown to function in mitotic checkpoint. Thus, Chk1 inhibitor is not expected to enhance the toxicity of paclitaxel. Here we show that downregulation of Chk1 sensitizes tumor cells to the toxicity of paclitaxel in cell proliferation assay. Fluorescence microscopy showed that Chk1 knockdown augments mitotic catastrophe and apoptosis in paclitaxel‐treated cancer cells. Further, we elucidated the mechanism of this sensitization. Chk1 inhibition facilitates paclitaxel‐induced M‐phase entry by activation of Cdc2 kinase and accumulation of cyclin B1, the required cofactor for Cdc2 kinase activity. Moreover, Chk1 downregulation inhibits M phase exit through induction of the anaphase inhibitor, securin/PDS1. Collectively, Chk1 elimination sustains a more effective mitotic arrest as demonstrated by the more efficient accumulation of M‐phase marker phospho‐histone H3. We show that Chk1 elimination attenuates the paclitaxel‐induced activation of the anti‐apoptotic p42/p44 (ERK1/2) MAP kinase pathway, additionally contributing to the sensitization. Our results suggest that in addition to its well‐established role as an enforcer of S and G2‐checkpoints in response to genotoxic stress, Chk1 also plays a protective role in mitotic checkpoint to lessen mitotic catastrophe and thereby limits cell‐death. Therefore Chk1 downregulation can not only potentiate DNA‐damaging agents, but also enhance the toxicity of anti‐microtubule agents, which significantly broadens its therapeutic applications. © 2005 Wiley‐Liss, Inc.
Residential and occupational exposure to 50‐Hz magnetic fields and brain tumours in Norway: A population‐based study
Authors: Klaeboe Lars , Blaasaas Karl Gerhard , Haldorsen Tor , Tynes Tore
Published: February 2005

Our case‐control study was conducted to investigate whether residential and occupational exposure to magnetic fields increased the risk for brain tumours in adults. Data from an occupational exposure matrix was also evaluated. The study population in this nested case‐control study was made up of subjects aged 16 years and older who had resided in a broad corridor around a high‐voltage power line in 1980 or during one of the years from 1986–1996. The cases were incident cases diagnosed during 1980–96. Two controls were matched to each case by year of birth, sex, municipality and first year entering the cohort. The time‐weighted average exposure to residential magnetic fields generated by the power lines was calculated for the exposure follow‐up from 1 January 1967 to diagnosis. In addition, job titles and branches of industry were classified as categories of hours per week in a magnetic field above background level (0.1 μT). Exposures were cumulated over occupationally active years for the exposure follow‐up from 1 January 1955 to diagnosis. When residential magnetic fields are evaluated, the 2 upper residential, time‐weighted, average magnetic field categories showed elevated odds ratios (ORs) for all brain tumours (OR = 1.6; 95% confidence interval [95%CI] 0.9–2.7 and OR = 1.3; 95% CI 0.7–2.3). Occupational exposure showed no association to exposure for any site. We found an elevated risk for residential exposure to magnetic fields and brain tumours, although the risk was not significant, and no clear exposure‐response pattern was found. The findings for the occupational exposure groups showed an inverse association. © 2005 Wiley‐Liss, Inc.
Natural history and screening model for high‐risk human papillomavirus infection, neoplasia and cervical cancer in the Netherlands
Authors: Berkhof Johannes , de Bruijne Martine C , Zielinski Gilda D , Meijer Chris JLM
Published: February 2005

A simulation model is presented that assumes that persistent infection with high‐risk human papillomavirus (hrHPV) is a necessary cause of cervical cancer. For the estimation of the model parameters, data of recent Dutch follow‐up studies were reanalyzed. The predicted incidences of cervical cancer, cervical intraepithelial neoplasia (CIN1, CIN2 and CIN3) and abnormal cytology were validated with nationwide figures and population‐based screening results. The model predicted a lifetime risk for cervical cancer of 2.9% with a peak at age 48 years. The predicted lifetime risk dropped to 0.4% when attending cervical screening. For women who were not hrHPV infected at 30 years, the lifetime risk was 1.6%. Sensitivity analyses were performed to check natural history assumptions that were only weakly identified from available data sets. The incidence of CIN3 observed with screening appeared a useful clinical end point as the predicted incidence was robust against changes in the sensitivity of cervical cytology and the duration to CIN3. The model can be used to study the health‐economic benefits that can be achieved in nationwide screening when including an hrHPV test. © 2005 Wiley‐Liss, Inc.
Oncolysis of human ovarian cancers by echovirus type 1
Authors: Shafren Darren R. , Sylvester Dianne , Johansson E. Susanne , Campbell Ian G. , Barry Richard D.
Published: February 2005

A small number of enteroviruses possess the capacity to induce rapid and marked lytic infections in cells of various human malignancies. During screening of representative human enteroviruses for their oncolytic capacity, we observed that echovirus type 1 (EV1) displayed a high level of tropism for human ovarian cancer cells. EV1 is an enterovirus which largely causes asymptomatic infections in humans and whose tissue tropism is primarily regulated via interactions with the I domain of the α subunit of cell surface–expressed integrin α2β1. We evaluated the capacity of wild‐type EV1 to act as an oncolytic agent of ovarian cancers propagated as cell monolayers, multicellular spheroids or xenografts in SCID mice. EV1 infection of in vitro propagated ovarian cell lines expressing high levels of integrin α2β1 was assessed for specific viral attachment, antibody blockade, induction of cytopathic effect and production of progeny virions. EV1 lytically infected all 8 human ovarian cancer cell lines tested (2008, DOV13, JAM, OVCA‐429, OVCAR‐3, OVHS‐1, OAW‐42 and IGROV‐1) but not the immortalized normal ovarian surface epithelial cell line (HOSE) or human PBMCs. EV1 challenge was equally effective in the oncolysis of human ovarian cancer cells whether in monolayer or spheroidal environments. The therapeutic efficacy of EV1 was demonstrated by rapid reduction of tumor burden by a single viral intratumoral injection in SCID mice bearing multiple preformed s.c. xenografts. Using an in vivo i.p. human ovarian cancer xenograft model, administration of EV1 was further shown to significantly inhibit the formation and burden of ascites tumors. These findings demonstrate an important proof of principle for employing wild‐type EV1 as a potential oncolytic agent in the control of human ovarian cancers. © 2005 Wiley‐Liss, Inc.
Effect of resveratrol on the development of spontaneous mammary tumors in HER‐2/neu transgenic mice
Authors: Provinciali Mauro , Re Francesca , Donnini Alessia , Orlando Fiorenza , Bartozzi Beatrice , Di Stasio Grazia , Smorlesi Arianna
Published: February 2005

Resveratrol (Res) has been reported to possess cancer chemopreventive activity on the basis of its in vitro effects on tumor cells and in vivo experimental models of rodents transplanted with parental tumors or treated with carcinogens. We investigated the effects of Res on the development of mammary tumors appearing spontaneously in HER‐2/neu transgenic mice at an early age. The mechanisms involved in the Res antitumor effect were evaluated by studying the immune effectiveness, tumor apoptosis and expression of mRNA and protein for HER‐2/neu in tumoral mammary glands from Res‐treated mice and in tumor cell lines. Res supplementation delayed the development of spontaneous mammary tumors (p < 0.001), reduced the mean number and size of mammary tumors (p < 0.0001) and diminished the number of lung metastases in HER‐2/neu transgenic mice. The effects of Res were associated with downregulation of HER‐2/neu gene expression and increased apoptosis both in tumoral mammary glands and in murine (N202) and human (SKBr3) tumor cell lines. Neither the basal, the IL‐2‐induced NK activity nor the lymphocyte number and proliferation was modified in Res‐supplemented compared to control mice. Our results demonstrate that Res supplementation delays the development and reduces the metastasizing capacity of spontaneous mammary tumors in HER‐2/neu transgenic mice. The antitumor effect of Res might be related to the downregulation of HER‐2/neu expression and the induction of apoptosis in tumor cells. © 2005 Wiley‐Liss, Inc.
Serial killing of tumor cells by cytotoxic T cells redirected with a CD19‐/CD3‐bispecific single‐chain antibody construct
Authors: Hoffmann Patrick , Hofmeister Robert , Brischwein Klaus , Brandl Christian , Crommer Sandrine , Bargou Ralf , Itin Christian , Prang Nadja , Baeuerle Patrick A.
Published: February 2005

Certain bispecific antibodies exhibit an extraordinary potency and efficacy for target cell lysis by eliciting a polyclonal T‐cell response. One example is a CD19‐/CD3‐bispecific single‐chain antibody construct (bscCD19xCD3), which at femtomolar concentrations can redirect cytotoxic T cells to eliminate human B lymphocytes, B lymphoma cell lines and patient‐derived malignant B cells. Here we have further explored the basis for this high potency. Using video‐assisted microscopy, bscCD19xCD3 was found to alter the motility and activity of T cells from a scanning to a killing mode. Individual T cells could eliminate multiple target cells within a 9 hr time period, resulting in nuclear fragmentation and membrane blebbing of target cells. Complete target cell elimination was observed within 24 hr at effector‐to‐target cell ratios as low as 1:5. Under optimal conditions, cell killing started within minutes after addition of bscCD19xCD3, suggesting that the rate of serial killing was mostly determined by T‐cell movement and target cell scanning and lysis. At all times, T cells remained highly motile, and no clusters of T and target cells were induced by the bispecific antibody. Bystanding target‐negative cells were not detectably affected. Repeated target cell lysis by bscCD19xCD3‐activated T cells increased the proportion of CD19/CD3 double‐positive T cells, which was most likely a consequence of transfer of CD19 from B to T cells during cytolytic synapse formation. To our knowledge, this is the first study showing that a bispecific antibody can sustain multiple rounds of target cell lysis by T cells. © 2005 Wiley‐Liss, Inc.
Identification and characterisation of the major aspartic proteinase activity in Theobroma cacao seeds
Authors: Guilloteau Martine , Laloi Maryse , Michaux Stephan , Bucheli Peter , McCarthy James
Published: February 2005

Theobroma cacao seeds contain an unusually high level of aspartic proteinase activity. Although this activity is central to the development of high‐quality cocoa flavour, the T cacao polypeptide responsible has not yet been definitively identified. Here we report the identification and characterisation of an active protein complex from T cacao seeds with an apparent molecular weight of approximately 50 kDa. This active complex contains at least two polypeptides: an approximately 30.5 kDa aspartic proteinase, the product of the TcAP2 gene, and an associated polypeptide, the 20.5 kDa trypsin inhibitor protein. The active complex co‐eluted off a size exclusion column with another complex containing the trypsin inhibitor and a putative acid chitinase. The 30.5 kDa TcAP2 proteinase is apparently a monomeric aspartic proteinase with optimal activity between 42 and 47 °C and an optimal pH of 3.0. Significant inactivation of the TcAP2 activity occurs at acid pH around 47–52 °C, a temperature potentially obtained during cocoa bean fermentation. SDS‐PAGE analysis showed that the purified TcAP2 complex efficiently degrades the cacao seed storage protein vicilin into peptides smaller than 10 kDa. In addition, high‐resolution size exclusion chromatography showed that this proteinase is capable of degrading proteins into peptides as small as di‐ and tripeptides, indicating for the first time that the main T cacao seed aspartic proteinase can produce very small peptide products. Our results demonstrate that the aspartic proteinase encoded by the TcAP2 gene plays a critical role in the production of cocoa flavour precursor peptides during cocoa bean fermentation. Copyright © 2005 Society of Chemical Industry
Melanosis inhibition and SO2 residual levels in shrimps (Parapenaeus longirostris) after different sulfite‐based treatments
Authors: Gómez‐Guillén M Carmen , Martínez‐Alvarez Óscar , Llamas Argimiro , Montero Pilar
Published: February 2005

The effectiveness of different sulfite‐based treatments to prevent melanosis in fresh deepwater pink shrimp (Parapenaeus longirostris) was evaluated. Increasing the concentration of sulfites, different methods of application (immersion and dust) and synergy with other compounds, such as citric acid and chelants, were investigated. The level of SO2 residues in the muscle was determined in a selection of the most effective treatments. One‐hour dip treatment with 50 g kg−1 sulfite, together with citric acid and chelants, was effective for melanosis prevention for at least one week. With this treatment, the statutory limit of 0.3 g kg−1 SO2 in edible part was not exceeded by the majority of samples analysed. Copyright © 2005 Society of Chemical Industry
Strikingly high content of grain protein in solution‐cultured rice
Authors: Qiuxia He , Qifa Zhou , Xuemei Sun
Published: February 2005

A greenhouse experiment was conducted to investigate the nutritional quality of solution‐cultured rice. Five rice cultivars, different in grain amylose content and protein content, were grown under 10, 40 and 80 mg l−1 nitrogen levels during the period of July 2003 to October 2003. In comparison to their original seeds, the solution‐cultured rice Oryza sativa L grain had strikingly higher protein content across all the cultivars and nitrogen levels, and remarkably lower amylose content in the waxy and low amylose cultivars, which might be due to the sufficiently stable nitrogen supply and well‐controlled temperature and humidity. The highest grain protein content was 163.6 g kg−1 in this experiment, which is the highest reported rice grain protein content. The residual nitrogen concentration was greater than 12.39 g kg−1 in the roots, 8.95 g kg−1 in the stems, and 21.97 g kg−1 in the flag leaves across all the cultivars and nitrogen treatments at harvesting. The rice grain had a narrow range of grain carbon content and hydrogen content. The average grain carbon and hydrogen contents for all the rice samples were 42.95 ± 0.15 (n = 60) and 6.81 ± 0.04 g kg−1 (n = 60), respectively. The solution cultured rice grain was characterized with lower carbon–nitrogen mole ratio and lower hydrogen–nitrogen mole ratio, which could be mainly attributed to the increased protein content. The response of plant nitrogen, grain protein and amylose concentration to the supplemental nitrogen level varied with the cultivars. The results in this study suggested that solution culture technology could improve the production potential of rice. Copyright © 2005 Society of Chemical Industry
Instrumental measurement of orange juice colour: a review
Authors: Meléndez‐Martínez Antonio Jesús , Vicario Isabel M. , Heredia Francisco J
Published: February 2005

Colour of orange juice is provided by carotenoids, which belong to one of the main classes of natural pigments, although the colour of particular orange varieties, blood oranges, is mainly due to anthocyanins. Colour of food influences consumers' preferences. For orange juices, some studies have revealed that the colour of citrus beverages in general is related to the consumer's perception of the quality of these products. The USA attaches great importance to the objective evaluation of orange juice colour, to the point that this attribute is evaluated for the commercial classification of the product on the basis of its quality. Apart from the importance of orange juice colour in relation to the quality of the product, it is important to accurately measure this parameter since it has been demonstrated that colour measurements can be used to estimate the carotenoid content rapidly for quality control purposes. Owing to this factors, several techniques and instruments have been developed over the years. This review assesses these methods and the results gained from them. Copyright © 2005 Society of Chemical Industry
Structure determination and conformation analysis of symmetrical dimers
Authors: Buevich Alexei V. , Chan Tze‐Ming , Wang C. H. , McPhail Andrew T. , Ganguly A. K.
Published: February 2005

Conformational and stereochemical analysis of six new symmetrical dimers was performed using proton–proton vicinal coupling measured from 1H NMR and 13C satellites of 1H NMR signals, natural abundance 13C‐edited nuclear overhauser effect (NOE) experiments, comprehensive NOE analysis and molecular modeling. The 13C satellite analysis and 13C‐edited NOE experiments were carried out to extract spectral information between equivalent protons. Molecular modeling was applied for estimations of three‐dimensional parameters of the studied dimers, which were subsequently used to generate a set of theoretical NOE for each possible conformation. The J‐coupling, 13C‐edited NOE and quantitative NOE analyses showed the predominance of gauche conformation for three dimers, whereas a mixture of gauche and anti conformations (45:55) for three other dimers was established by quantitative NOE analysis. X‐ray crystallographic study confirmed the stereochemistry of one of the dimers and revealed a discrepancy in conformation stability between liquid and solid states. Copyright © 2004 John Wiley & Sons, Ltd.