bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control and maintenance of mammalian cell size
Authors: Cooper Stephen 
Published: October 2004

Abstract
Background
Conlon and Raff propose that mammalian cells grow linearly during the division cycle. According to Conlon and Raff, cells growing linearly do not need a size checkpoint to maintain a constant distribution of cell sizes. If there is no cell-size-control system, then exponential growth is not allowed, as exponential growth, according to Conlon and Raff, would require a cell-size-control system.

Discussion
A reexamination of the model and experiments of Conlon and Raff indicates that exponential growth is fully compatible with cell size maintenance, and that mammalian cells have a system to regulate and maintain cell size that is related to the process of S-phase initiation. Mammalian cell size control and its relationship to growth rate–faster growing cells are larger than slower growing cells–is explained by the initiation of S phase occurring at a relatively constant cell size coupled with relatively invariant S- and G2-phase times as interdivision time varies.

Summary
This view of the mammalian cell cycle, the continuum model, explains the mass growth pattern during the division cycle, size maintenance, size determination, and the kinetics of cell-size change following a shift-up from slow to rapid growth.
Intracellular shuttling of a Drosophila APC tumour suppressor homolog
Authors: Cliffe Adam , Mieszczanek Julius , Bienz Mariann 
Published: October 2004

Abstract
Background
The Adenomatous polyposis coli (APC) tumour suppressor is found in multiple discrete subcellular locations, which may reflect sites of distinct functions. In Drosophila epithelial cells, the predominant APC relative (E-APC) is concentrated at the apicolateral adherens junctions. Genetic analysis indicates that this junctional association is critical for the function of E-APC in Wnt signalling and in cellular adhesion. Here, we ask whether the junctional association of E-APC is stable, or whether E-APC shuttles between the plasma membrane and the cytoplasm.

Results
We generated a Drosophila strain that expresses E-APC (dAPC2) tagged with green fluorescent protein (GFP-E-APC) and we analysed its junctional association with fluorescence recovery after photobleaching (FRAP) experiments in live embryos. This revealed that the junctional association of GFP-E-APC in epithelial cells is highly dynamic, and is far less stable than that of the structural components of the adherens junctions, E-cadherin, α-catenin and Armadillo. The shuttling of GFP-E-APC to and from the plasma membrane is unaltered in mutants of Drosophila glycogen synthase kinase 3 (GSK3), which mimic constitutive Wingless signalling. However, the stability of E-APC is greatly reduced in these mutants, explaining their apparent delocalisation from the plasma membrane as previously observed. Finally, we show that GFP-E-APC forms dynamic patches at the apical plasma membrane of late embryonic epidermal cells that form denticles, and that it shuttles up and down the axons of the optic lobe.

Conclusions
We conclude that E-APC is a highly mobile protein that shuttles constitutively between distinct subcellular locations.
Evolution and distribution of RNA polymerase II regulatory sites from RNA polymerase III dependant mobile Alu elements
Authors: Shankar Ravi , Grover Deepak , Brahmachari Samir K , Mukerji Mitali 
Published: October 2004

Abstract
Background
The primate-specific Alu elements, which originated 65 million years ago, exist in over a million copies in the human genome. These elements have been involved in genome shuffling and various diseases not only through retrotransposition but also through large scale Alu-Alu mediated recombination. Only a few subfamilies of Alus are currently retropositionally active and show insertion/deletion polymorphisms with associated phenotypes. Retroposition occurs by means of RNA intermediates synthesised by a RNA polymerase III promoter residing in the A-Box and B-Box in these elements. Alus have also been shown to harbour a number of transcription factor binding sites, as well as hormone responsive elements. The distribution of Alus has been shown to be non-random in the human genome and these elements are increasingly being implicated in diverse functions such as transcription, translation, response to stress, nucleosome positioning and imprinting.

Results
We conducted a retrospective analysis of putative functional sites, such as the RNA pol III promoter elements, pol II regulatory elements like hormone responsive elements and ligand-activated receptor binding sites, in Alus of various evolutionary ages. We observe a progressive loss of the RNA pol III transcriptional potential with concomitant accumulation of RNA pol II regulatory sites. We also observe a significant over-representation of Alus harboring these sites in promoter regions of signaling and metabolism genes of chromosome 22, when compared to genes of information pathway components, structural and transport proteins. This difference is not so significant between functional categories in the intronic regions of the same genes.

Conclusions
Our study clearly suggests that Alu elements, through retrotransposition, could distribute functional and regulatable promoter elements, which in the course of subsequent selection might be stabilized in the genome. Exaptation of regulatory elements in the preexisting genes through Alus could thus have contributed to evolution of novel regulatory networks in the primate genomes. With such a wide spectrum of regulatory sites present in Alus, it also becomes imperative to screen for variations in these sites in candidate genes, which are otherwise repeat-masked in studies pertaining to identification of predisposition markers.
Generation of competent bone marrow-derived antigen presenting cells from the deer mouse (Peromyscus maniculatus)
Authors: Davenport Bennett J , Willis Derall G , Prescott Joseph , Farrell Regina M , Coons Teresa A , Schountz Tony 
Published: October 2004

Abstract
Background
Human infections with Sin Nombre virus (SNV) and related New World hantaviruses often lead to hantavirus cardiopulmonary syndrome (HCPS), a sometimes fatal illness. Lungs of patients who die from HCPS exhibit cytokine-producing mononuclear infiltrates and pronounced pulmonary inflammation. Deer mice (Peromyscus maniculatus) are the principal natural hosts of SNV, in which the virus establishes life-long persistence without conspicuous pathology. Little is known about the mechanisms SNV employs to evade the immune response of deer mice, and experimental examination of this question has been difficult because of a lack of methodologies for examining such responses during infection. One such deficiency is our inability to characterize T cell responses because susceptible syngeneic deer mice are not available.

Results
To solve this problem, we have developed an in vitro method of expanding and generating competent antigen presenting cells (APC) from deer mouse bone marrow using commercially-available house mouse (Mus musculus) granulocyte-macrophage colony stimulating factor. These cells are capable of processing and presenting soluble protein to antigen-specific autologous helper T cells in vitro. Inclusion of antigen-specific deer mouse antibody augments T cell stimulation, presumably through Fc receptor-mediated endocytosis.

Conclusions
The use of these APC has allowed us to dramatically expand deer mouse helper T cells in culture and should permit extensive characterization of T cell epitopes. Considering the evolutionary divergence between deer mice and house mice, it is probable that this method will be useful to other investigators using unconventional models of rodent-borne diseases.
Enhancement of blood-tumor barrier permeability by Sar-[D-Phe8]des-Arg9BK, a metabolically resistant bradykinin B1 agonist, in a rat C6 glioma model
Authors: Cardoso Ronie Cleverson , Lobão-Soares Bruno , Bianchin Marino Muxfeldt , Carlotti Carlos Gilberto , Walz Roger , Alvarez-Silva Márcio , Trentin Andréa Gonçalves , Nicolau Mauro 
Published: October 2004

Abstract
Background
While it is well known that bradykinin B2 agonists increase plasma protein extravasation (PPE) in brain tumors, the bradykinin B1 agonists tested thus far are unable to produce this effect. Here we examine the effect of the selective B1 agonist bradykinin (BK) Sar-[D-Phe8]des-Arg9BK (SAR), a compound resistant to enzymatic degradation with prolonged activity on PPE in the blood circulation in the C6 rat glioma model.

Results
SAR administration significantly enhanced PPE in C6 rat brain glioma compared to saline or BK (p < 0.01). Pre-administration of the bradykinin B1 antagonist [Leu8]-des-Arg (100 nmol/Kg) blocked the SAR-induced PPE in the tumor area.

Conclusions
Our data suggest that the B1 receptor modulates PPE in the blood tumor barrier of C6 glioma. A possible role for the use of SAR in the chemotherapy of gliomas deserves further study.
Peroxynitrite decomposition catalyst ameliorates renal damage and protein nitration in cisplatin-induced nephrotoxicity in rats
Authors: Chirino Yolanda I , Hernández-Pando Rogelio , Pedraza-Chaverrí José 
Published: October 2004

Abstract
Background
Oxidative stress is involved in cisplatin-nephrotoxicity. However, it has not completely established if reactive nitrogen species and nitrosative stress are involved in this experimental model. The purpose of this work was to study the role of peroxynitrite, a reactive nitrogen specie, in cisplatin-nephrotoxicity using the compound 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron (III) (FeTPPS), a soluble complex able to metabolize peroxynitrite.

Results
In rats treated with cisplatin (a single intraperitoneal dose of 7.5 mg/kg body weight), renal nitrosative stress was made evident by the increase in 3-nitrotyrosine on day 3. In addition, cisplatin-induced nephrotoxicity was evident by the histological damage of proximal tubular cells and by the increase in (a) serum creatinine, (b) blood urea nitrogen, and (c) urinary excretion of N-acetyl-β-D-glucosaminidase and total protein. Cisplatin-induced nitrosative stress and nephrotoxicity were attenuated by FeTPPS-treatment (15 mg/kg body weight, intraperitoneally, every 12 hours for 3 days).

Conclusions
Nitrosative stress is involved in cisplatin-induced nephrotoxicity in rats. Our data suggest that peroxynitrite is involved, at least in part, in cisplatin-induced nephrotoxicity and protein nitration.
Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2
Authors: Blaney Joseph E , Hanson Christopher T , Hanley Kathryn A , Murphy Brian R , Whitehead Stephen S 
Published: October 2004

Abstract
Background
A dengue virus type 2 (DEN-2 Tonga/74) isolated from a 1974 epidemic was characterized by mild illness and belongs to the American genotype of DEN-2 viruses. To prepare a vaccine candidate, a previously described 30 nucleotide deletion (Δ30) in the 3' untranslated region of DEN-4 has been engineered into the DEN-2 isolate.

Methods
A full-length cDNA clone was generated from the DEN-2 virus and used to produce recombinant DEN-2 (rDEN-2) and rDEN2Δ30. Viruses were evaluated for replication in SCID mice transplanted with human hepatoma cells (SCID-HuH-7 mice), in mosquitoes, and in rhesus monkeys. Neutralizing antibody induction and protective efficacy were also assessed in rhesus monkeys.

Results
The rDEN2Δ30 virus was ten-fold reduced in replication in SCID-HuH-7 mice when compared to the parent virus. The rDEN-2 viruses were not infectious for Aedes mosquitoes, but both readily infected Toxorynchites mosquitoes. In rhesus monkeys, rDEN2Δ30 appeared to be slightly attenuated when compared to the parent virus as measured by duration and peak of viremia and neutralizing antibody induction. A derivative of rDEN2Δ30, designated rDEN2Δ30-4995, was generated by incorporation of a point mutation previously identified in the NS3 gene of DEN-4 and was found to be more attenuated than rDEN2Δ30 in SCID-HuH-7 mice.

Conclusions
The rDEN2Δ30 and rDEN2Δ30-4995 viruses can be considered for evaluation in humans and for inclusion in a tetravalent dengue vaccine.
Renal outcome in adults with renal insufficiency and irregular asymmetric kidneys
Authors: Neild Guy H , Thomson Gill , Nitsch Dorothea , Woolfson Robin G , Connolly John O , Woodhouse Christopher RJ 
Published: October 2004

Abstract
Background
The commonest cause of end-stage renal failure (ESRF) in children and young adults is congenital malformation of the kidney and urinary tract. In this retrospective review, we examine whether progression to ESRF can be predicted and whether treatment with angiotensin converting enzyme inhibitors (ACEI) can delay or prevent this.

Methods
We reviewed 78 patients with asymmetric irregular kidneys as a consequence of either primary vesico-ureteric reflux or renal dysplasia (Group 1, n = 44), or abnormal bladder function (Group 2, n = 34). Patients (median age 24 years) had an estimated GFR (eGFR) < 60 ml/min/1.73 m2 with at least 5 years of follow up (median 143 months). 48 patients received ACEI. We explored potential prognostic factors that affect the time to ESRF using Cox-regression analyses.

Results
At start, mean (SE) creatinine was 189 (8) μmol/l, mean eGFR 41 (1) ml/min 1.73 m2, mean proteinuria 144 (14) mg/mmol creatinine (1.7 g/24 hrs). Of 78 patients, 36 (46%) developed ESRF, but none of 19 with proteinuria less than 50 mg/mmol and only two of 18 patients with eGFR above 50 ml/min did so. Renal outcome between Groups 1 and 2 appeared similar with no evidence for a difference. A benefit in favour of treatment with ACEI was observed above an eGFR of 40 ml/min (p = 0.024).

Conclusion
The similar outcome of the two groups supports the nephrological nature of progressive renal failure in young men born with abnormal bladders. There is a watershed GFR of 40–50 ml/min at which ACEI treatment can be successful at improving renal outcome.
Psychosocial correlates with depressive symptoms six years after a first episode of psychosis as compared with findings from a general population sample
Authors: Forsell Yvonne , Levander Sonja , Cullberg Johan 
Published: October 2004

Abstract
Background
Depression is frequently occurring during and after psychosis. The aim of this study was to analyze if the psychosocial characteristics associated with depression/depressive symptoms in the late phase of a first episode psychosis (FEP) population were different compared to persons from the general population.

Methods
A questionnaire was sent out to all individuals six years after their FEP and to a general population sample. Depressive symptoms were recorded using a self-rating scale, the Major Depression Inventory.

Results
Formerly FEP persons had a higher representation of depressive symptoms/depression, unemployment, financial problems and insufficient social network. Depressive symptoms/depression were found to be associated with psychosocial problems. An age and gender effect was found in the general population, but not in the FEP sample. When the psychosocial characteristics were taken into account there were no association between having had FEP and depressive symptoms.

Conclusions
The association between having been a FEP patient and depressive symptoms/depression disappeared when negative social aspects were taken into account.
Fear of nuclear war increases the risk of common mental disorders among young adults: a five-year follow-up study
Authors: Poikolainen Kari , Aalto-Setälä Terhi , Tuulio-Henriksson Annamari , Marttunen Mauri , Lönnqvist Jouko 
Published: October 2004

Abstract
Background
Evidence on the relation between fear of war and mental health is insufficient. We carried out a prospective cohort study to find out whether fear of nuclear war is related to increased risk of common mental disorders.

Methods
Within two months preceding the outbreak of Persian Gulf War in January 1991, 1518 adolescents [mean age 16.8 years, SD 0.9] filled in a self-administered questionnaire. Of the 1493 respondents, 47% gave their written informed consent to participate in the follow-up study. There were no material differences between those who chose to respond anonymously and those who volunteered to give their name and address for the follow-up study. In 1995, the response to the follow-up questionnaire was 92%. Common mental disorders were assessed by 36-item version of the General Health Questionnaire [GHQ]. A score 5 or higher was considered to indicate caseness. We excluded 23 cases which had used mental health services in the year 1991 or earlier and two cases with deficient responses to GHQ. This left 626 subjects for analysis [400 women].

Results
After adjusting for significant mental health risk factors in logistic regression analysis, the risk for common mental disorders was found to be significantly related to the increasing frequency of fear for nuclear war, high scores of trait anxiety and high scores of immature defense style. Elevated risk was confined to the group reporting fear of nuclear war once a week or more often [odds ratio 2.05; 95% confidence interval 1.29–3.27].

Conclusion
Frequent fear of nuclear war in adolescents seems to be an indicator for an increased risk for common mental disorders and deserves serious attention.
Targeting smoking cessation to high prevalence communities: outcomes from a pilot intervention for gay men
Authors: Harding Richard , Bensley James , Corrigan Nick 
Published: October 2004

Abstract
Background
Cigarette smoking prevalence among gay men is twice that of population levels. A pilot community-level intervention was developed and evaluated aiming to meet UK Government cessation and cancer prevention targets.

Methods
Four 7-week withdrawal-oriented treatment groups combined nicotine replacement therapy with peer support. Self-report and carbon monoxide register data were collected at baseline and 7 weeks. N = 98 gay men were recruited through community newspapers and organisations in London UK.

Results
At 7 weeks, n = 44 (76%) were confirmed as quit using standard UK Government National Health Service monitoring forms. In multivariate analysis the single significant baseline variable associated with cessation was previous number of attempts at quitting (OR 1.48, p = 0.04).

Conclusions
This tailored community-level intervention successfully recruited a high-prevalence group, and the outcome data compares very favourably to national monitoring data (which reports an average of 53% success). Implications for national targeted services are considered.
Day-to-day variations during clinical drug monitoring of morphine, morphine-3-glucuronide and morphine-6-glucuronide serum concentrations in cancer patients. A prospective observational study
Authors: Klepstad Pål , Hilton Priscilla , Moen Jorunn , Kaasa Stein , Borchgrevink Petter C , Zahlsen Kolbjørn , Dale Ola 
Published: October 2004

Abstract
Background
The feasibility of drug monitoring of serum concentrations of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) during chronic morphine therapy is not established. One important factor relevant to drug monitoring is to what extent morphine, M6G and M3G serum concentrations fluctuate during stable morphine treatment.

Methods
We included twenty-nine patients admitted to a palliative care unit receiving oral morphine (n = 19) or continuous subcutaneous (sc) morphine infusions (n = 10). Serum concentrations of morphine, M6G and M3G were obtained at the same time on four consecutive days. If readmitted, the patients were followed for another trial period. Day-to-day variations in serum concentrations and ratios were determined by estimating the percent coefficient of variation (CV = (mean/SD) ×100).

Results
The patients' median morphine doses were 90 (range; 20–1460) mg/24 h and 135 (range; 30–440) mg/24 h during oral and sc administration, respectively. Intraindividual fluctuations of serum concentrations estimated by median coefficients of day-to-day variation were in the oral group for morphine 46%, for M6G 25% and for M3G 18%. The median coefficients of variation were lower in patients receiving continuous sc morphine infusions (morphine 10%, M6G 13%, M3G 9%).

Conclusion
These findings indicate that serum concentrations of morphine and morphine metabolites fluctuate. The fluctuations found in our study are not explained by changes in morphine doses, administration of other drugs or by time for collection of blood samples. As expected the day-to-day variation was lower in patients receiving continuous sc morphine infusions compared with patients receiving oral morphine.
Under-representation of developing countries in the research literature: ethical issues arising from a survey of five leading medical journals
Authors: Sumathipala Athula , Siribaddana Sisira , Patel Vikram 
Published: October 2004

Abstract
Background
It is widely acknowledged that there is a global divide on health care and health research known as the 10/90 divide.

Methods
A retrospective survey of articles published in the BMJ, Lancet, NEJM, Annals of Internal Medicine & JAMA in a calendar year to examine the contribution of the developing world to medical literature. We categorized countries into four regions: UK, USA, Other Euro-American countries (OEAC) and (RoW). OEAC were European countries other than the UK but including Australia, New Zealand and Canada. RoW comprised all other countries.

Results
The average contribution of the RoW to the research literature in the five journals was 6.5%. In the two British journals 7.6% of the articles were from the RoW; in the three American journals 4.8% of articles were from RoW. The highest proportion of papers from the RoW was in the Lancet (12%). An analysis of the authorship of 151 articles from RoW showed that 104 (68.9%) involved authorship with developed countries in Europe or North America. There were 15 original papers in these journals with data from RoW but without any authors from RoW.

Conclusions
There is a marked under-representation of countries in high-impact general medical journals. The ethical implications of this inequity and ways of reducing it are discussed.