bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective antiprotease-antibiotic treatment of experimental anthrax
Authors: Popov Serguei G , Popova Taissia G , Hopkins Svetlana , Weinstein Raymond S , MacAfee Rebecca , Fryxell Karl J , Chandhoke Vikas , Bailey Charles , Alibek Ken
Published: April 2005

Background

Inhalation anthrax is characterized by a systemic spread of the challenge agent,Bacillus anthracis. It causes severe damage, including multiple hemorrhagic lesions, to host tissues and organs. It is widely believed that anthrax lethal toxin secreted by proliferating bacteria is a major cause of death, however, the pathology of intoxication in experimental animals is drastically different from that found during the infectious process. In order to close a gap between our understanding of anthrax molecular pathology and the most prominent clinical features of the infectious process we undertook bioinformatic and experimental analyses of potential proteolytic virulence factors ofB. anthracisdistinct from lethal toxin.

Methods

Secreted proteins (other than lethal and edema toxins) produced byB. anthraciswere tested for tissue-damaging activity and toxicity in mice. Chemical protease inhibitors and rabbit immune sera raised againstB. anthracisproteases were used to treat mice challenged withB. anthracis(Sterne) spores.

Results

B. anthracisstrain delta Ames (pXO1-, pXO2-) producing no lethal and edema toxins secrets a number of metalloprotease virulence factors upon cultivation under aerobic conditions, including those with hemorrhagic, caseinolytic and collagenolytic activities, belonging to M4 and M9 thermolysin and bacterial collagenase families, respectively.

These factors are directly toxic to DBA/2 mice upon intratracheal administration at 0.5 mg/kg and higher doses. Chemical protease inhibitors (phosphoramidon and 1, 10-phenanthroline), as well as immune sera against M4 and M9 proteases ofB. anthracis, were used to treat mice challenged withB. anthracis(Sterne) spores. These substances demonstrate a substantial protective efficacy in combination with ciprofloxacin therapy initiated as late as 48 h post spore challenge, compared to the antibiotic alone.

Conclusion

Secreted proteolytic enzymes are important pathogenic factors ofB. anthrasis, which can be considered as effective therapeutic targets in the development of anthrax treatment and prophylactic approaches complementing anti-lethal toxin therapy.
Diffusion and dissemination of evidence-based dietary srategies for the prevention of cancer
Authors: Ciliska Donna , Robinson Paula , Armour Tanya , Ellis Peter , Brouwers Melissa , Gauld Mary , Baldassarre Fulvia , Raina Parminder
Published: April 2005

Objective

The purpose was to determine what strategies have been evaluated to disseminate cancer control interventions that promote the uptake of adult healthy diet?

Methods

A systematic review was conducted. Studies were identified by searching MEDLINE, PREMEDLINE, Cancer LIT, EMBASE/Excerpta Medica, PsycINFO, CINAHL, the Cochrane Database of Systematic Reviews, and reference lists and by contacting technical experts. English-language primary studies were selected if they evaluated the dissemination of healthy diet interventions in individuals, healthcare providers, or institutions. Studies of children or adolescents only were excluded.

Results

One hundred one articles were retrieved for full text screening. Nine reports of seven distinct studies were included; four were randomized trials, one was a cohort design and three were descriptive studies. Six studies were rated as methodologically weak, and one was rated as moderate. Studies were not meta-analyzed because of heterogeneity, low methodological quality, and incomplete data reporting. No beneficial dissemination strategies were found except one that looks promising, the use of peer educators in the worksite, which led to a short-term increase in fruit and vegetable intake.

Conclusions and Implications

Overall, the quality of the evidence is not strong and is primarily descriptive rather than evaluative. No clear conclusions can be drawn from these data. Controlled studies are needed to evaluate dissemination strategies, and to compare dissemination and diffusion strategies with different messages and different target audiences.
Location of DNA damage by charge exchanging repair enzymes: effects of cooperativity on location time
Authors: Eriksen Kasper Astrup
Published: April 2005

Background

How DNA repair enzymes find the relatively rare sites of damage is not known in great detail. Recent experiments and molecular data suggest that individual repair enzymes do not work independently of each other, but interact with each other through charges exchanged along the DNA. A damaged site in the DNA hinders this exchange. The hypothesis is that the charge exchange quickly liberates the repair enzymes from error-free stretches of DNA. In this way, the sites of damage are located more quickly; but how much more quickly is not known, nor is it known whether the charge exchange mechanism has other observable consequences.

Results

Here the size of the speed-up gained from this charge exchange mechanism is calculated and the characteristic length and time scales are identified. In particular, for Escherichia coli, I estimate the speed-up is 50000/N, where N is the number of repair enzymes participating in the charge exchange mechanism. Even though N is not exactly known, a speed-up of order 10 is not entirely unreasonable. Furthermore, upon over expression of all the repair enzymes, the location time only varies as N-1/2 and not as 1/N.

Conclusion

The revolutionary hypothesis that DNA repair enzymes use charge exchange along DNA to locate damaged sites more efficiently is actually sound from a purely theoretical point of view. Furthermore, the predicted collective behavior of the location time is important in assessing the impact of stress-ful and radioactive environments on individual cell mutation rates.
Differential effect of obesity on bone mineral density in White, Hispanic and African American women: a cross sectional study
Authors: Castro Jonathan P , Joseph Linda A , Shin John J , Arora Surender K , Nicasio John , Shatzkes Joshua , Raklyar Irina , Erlikh Irina , Pantone Vincent , Bahtiyar Gul , Chandler Leon , Pabon Lina , Choudhry Sara , Ghadiri Nilofar , Gosukonda Pramodini , Muniyappa Rangnath , von-Gicyzki Hans , McFarlane Samy I
Published: April 2005

Osteoporosis is a major public health problem with low bone mass affecting nearly half the women aged 50 years or older. Evidence from various studies has shown that higher body mass index (BMI) is a protective factor for bone mineral density (BMD). Most of the evidence, however, is from studies with Caucasian women and it is unclear to what extent ethnicity plays a role in modifying the effect of BMI on BMD.

A cross sectional study was performed in which records of postmenopausal women who presented for screening for osteoporosis at 2 urban medical centres were reviewed. Using logistic regression, we examined the interaction of race and BMI after adjusting for age, family history of osteoporosis, maternal fracture, smoking, and sedentary lifestyle on BMD. Low BMD was defined as T-score at the lumbar spine < -1.

Among 3,206 patients identified, the mean age of the study population was 58.3 ± 0.24 (Years ± SEM) and the BMI was 30.6 kg/m2. 2,417 (75.4%) were African Americans (AA), 441(13.6%) were Whites and 348 (10.9%) were Hispanics. The AA women had lower odds of having low BMD compared to Whites [Odds ratio (OR) = 0.079 (0.03–0.24) (95% CI), p < 0.01]. The odds ratio of low BMD was not statistically significant between White and Hispanic women. We examined the interaction between race and BMD. For White women; as the BMI increases by unity, the odds of low BMD decreases [OR = 0.9 (0.87–0.94), p < 0.01; for every unit increase in BMI]. AA women had slightly but significantly higher odds of low BMD compared to Whites [OR 1.015 (1.007–1.14), p <0.01 for every unit increase in BMI]. This effect was not observed when Hispanic women were compared to Whites.

There is thus a race-dependent effect of BMI on BMD. With each unit increase in BMI, BMD increases for White women, while a slight but significant decrease in BMD occurs in African American women.
Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivodetection of mammary tumors and multiple metastases in immune deficient mice
Authors: Jenkins Darlene E , Hornig Yvette S , Oei Yoko , Dusich Joan , Purchio Tony
Published: April 2005

Introduction

Our goal was to generate xenograft mouse models of human breast cancer based on luciferase-expressing MDA-MB-231 tumor cells that would provide rapid mammary tumor growth; produce metastasis to clinically relevant tissues such as lymph nodes, lung, and bone; and permit sensitive in vivo detection of both primary and secondary tumor sites by bioluminescent imaging.

Method

Two clonal cell sublines of human MDA-MB-231 cells that stably expressed firefly luciferase were isolated following transfection of the parental cells with luciferase cDNA. Each subline was passaged once or twice in vivo to enhance primary tumor growth and to increase metastasis. The resulting luciferase-expressing D3H1 and D3H2LN cells were analyzed for long-term bioluminescent stability, primary tumor growth, and distal metastasis to lymph nodes, lungs, bone and soft tissues by bioluminescent imaging. Cells were injected into the mammary fat pad of nude and nude-beige mice or were delivered systemically via intracardiac injection. Metastasis was also evaluated by ex vivo imaging and histologic analysis postmortem.

Results

The D3H1 and D3H2LN cell lines exhibited long-term stable luciferase expression for up to 4–6 months of accumulative tumor growth time in vivo. Bioluminescent imaging quantified primary mammary fat pad tumor development and detected early spontaneous lymph node metastasis in vivo. Increased frequency of spontaneous lymph node metastasis was observed with D3H2LN tumors as compared with D3H1 tumors. With postmortem ex vivo imaging, we detected additional lung micrometastasis in mice with D3H2LN mammary tumors. Subsequent histologic evaluation of tissue sections from lymph nodes and lung lobes confirmed spontaneous tumor metastasis at these sites. Following intracardiac injection of the MDA-MB-231-luc tumor cells, early metastasis to skeletal tissues, lymph nodes, brain and various visceral organs was detected. Weekly in vivo imaging data permitted longitudinal analysis of metastasis at multiple sites simultaneously. Ex vivo imaging data from sampled tissues verified both skeletal and multiple soft tissue tumor metastasis.

Conclusion

This study characterized two new bioluminescent MDA-MB-231-luc human breast carcinoma cell lines with enhanced tumor growth and widespread metastasis in mice. Their application to current xenograft models of breast cancer offers rapid and highly sensitive detection options for preclinical assessment of anticancer therapies in vivo.
Differential Regulation of Sodium/Iodide Symporter Gene Expression by Nuclear Receptor Ligands in MCF-7 Breast Cancer Cells
Authors: Kogai Takahiko , Kanamoto Yoko , Li Andrew I. , Che Lisa H. , Ohashi Emi , Taki Katsumi , Chandraratna Roshantha A. , Saito Tsukasa , Brent Gregory A.
Published: April 2005

The sodium/iodide symporter (NIS) mediates iodide uptake in lactating breast tissue and is expressed in some breast cancers. We have previously demonstrated that all-trans retinoic acid (tRA) stimulates NIS gene expression and the selective cytotoxic effect of β-emitting radioiodide-131 (131I) in both in vitro and in vivo MCF-7 breast cancer cell systems. We studied the ability of natural and synthetic retinoids, in combination with other nuclear receptor ligands, to achieve greater and more sustained induction of NIS in MCF-7 cells and enhance 131I-mediated cytotoxicity. Selective stimulation of retinoic acid receptor (RAR) β/γ produced marked NIS induction; and selective stimulation of RARα, RARγ, or retinoid X receptor produced more modest induction. Maximal NIS induction was seen with 9-cis retinoic acid and AGN190168, a RAR β/γ-agonist. Dexamethasone (Dex), but not the other nuclear receptor ligands, in combination with tRA synergistically induced iodide uptake and NIS mRNA expression, predominantly by prolonging NIS mRNA half-life. The addition of Dex reduced the EC50 of tRA for NIS stimulation to approximately 7%, such that 10 −7m tRA with addition of Dex enhanced iodide uptake and selective cytotoxicity of 131I greater than 10−6m tRA alone. AGN190168 combined with Dex synergistically increased iodide uptake and significantly prolonged induction (5 d) of iodide uptake compared with that induced by the combination of tRA/Dex or 9-cis retinoic acid/Dex. The addition of Dex reduced the effective dose of retinoid and prolonged the induction of NIS, especially with AGN190168, suggesting higher efficacy of 131I after combination treatment.
Differential Expression of Procollagen Lysine 2-Oxoglutarate 5-Deoxygenase and Matrix Metalloproteinase Isoforms in Hypothyroid Rat Ovary and Disintegration of Extracellular Matrix
Authors: Saha Samir Kumar , Ghosh Pamela , Konar Aditya , Bhattacharya Samir , Roy Sib Sankar
Published: April 2005

Hypothyroid-induced reproductive malfunction in both the sexes is a common phenomenon of global concern. In an attempt to characterize the differentially expressed genes that might be responsible for these disorders, we have identified a number of clones in hypothyroid rat ovary by subtractive hybridization. One such clone is procollagen lysyl hydroxylase2 (Plod-2), the key enzyme for the first step of collagen biosynthetic pathway, which was down-regulated in hypothyroid condition. We have also demonstrated the reduced expression of other isoforms of Plods, namely Plod-1 and -3 in hypothyroid rat ovary. The current studies are the first of their kind to report that thyroid hormone regulates the Plod gene in rat ovary. Moreover, we have shown the up-regulation of matrix-degrading enzyme(s), matrix metalloproteinase(s) in the hypothyroid rat ovary, whereas the tissue-inhibitory metalloproteinase is down-regulated. Finally, the results of the present studies indicate that in hypothyroid condition, collagen biosynthesis in ovary seems to be disturbed with concomitant enhancement in collagen degradation, resulting in disintegration of overall ovarian structure.
Micelle Formation and Surface Adsorption of Octaethylene Glycol Monoalkyl Ether (CnE8)
Authors: Rusdi Muhammad , Moroi Yoshikiyo , Hlaing Thein , Matsuoka Keisuke
Published: April 2005

The surface tension was measured against the concentration of CnE8 (n = 14, 16, and 18) at temperatures of 298.2, 303.2, 308.2, 313.2, and 318.2 K, from which the critical micelle concentration (CMC) was determined. The CMC decreased with increasing carbon number at lower temperatures, where the decreasing rate became much smaller at higher temperatures. The CMC values were examined by pyrene fluorescence, and the I1/I3 ratio of the pyrene spectrum steeply decreased below the CMC, and finally reached a plateau at higher surfactant concentrations. The I1/I3 ratios indicate that the microenvironment of pyrene in the micellar region becomes more hydrophobic with increasing the alkyl chain of CnE8. The aggregation number by a static light-scattering method increased with increasing the alkyl chain at a definite temperature and with raising the temperature for all of the surfactants. The thermodynamic parameters (ΔG°, ΔH°, TΔS°) of the micelle formation were calculated from the temperature dependence of CMC and the aggregation number, and the micellization was found to be entropy-driven. The surface excess concentration (Γ) was also determined from the change in the surface tension with the concentration from which the molecular surface area (A) below the CMC was evaluated. The molecular surface areas suggest that longer monoalkyl ethers form a bi-molecular layer with the hydrophobic tail intruding inwards. The positive entropy change (Δs) for the surface adsorption decreased and stayed almost constant with increasing concentration for C14E8 and C16E8, while the change remained almost zero for C18E8 at whole concentrations below the CMC. These results suggest that the non-fully extended alkyl chain in the bulk could not well contribute to a positive entropy change upon adsorption, which results in a smaller decreasing rate in CMC with increasing carbon number of alkylchain for C16E8 and C18E8 compared with the decreasing rate for CnE8 with n less than 14.
One-Range Addition Theorems for Yukawa-Like Central and Noncentral Interaction Potentials and Their Derivatives
Authors: Guseinov I I
Published: April 2005

Using addition theorems for Slater-type orbitals, obtained by the author with the help of complete orthonormal sets of Ψα-Exponential type orbitals (α = 1, 0, −1, −2, ...), the one-range addition theorems for arbitrary Yukawa-like central and noncentral interaction potentials and their first and second derivatives are established. The addition theorems derived for the interaction potentials and the Slater orbitals are especially useful for machine computations of arbitrary multielectron multicenter integrals that arise in the Hartree–Fock–Roothaan approximation, and also in the Hylleraas-correlated wave-function method, which play a significant role in the theory and applications to quantum mechanics of atoms, molecules, and solids. The obtained relationships are valid for arbitrary nonzero screening constants of the potentials.
Multielement Determination of Trace Metals in Seawater by Inductively Coupled Plasma Mass Spectrometry after Tandem Preconcentration Using a Chelating Resin
Authors: Zhu Yanbei , Itoh Akihide , Fujimori Eiji , Umemura Tomonari , Haraguchi Hiroki
Published: April 2005

A tandem preconcentration method using a chelating resin was exploited for simultaneous multielement determination of trace metals in seawater by inductively coupled plasma mass spectrometry (ICP-MS). In the first preconcentration step, 500 mL of seawater sample was adjusted to pH 6.0, and the adsorption of trace metals on 0.4 g of Chelex-100 resin in dry weight was carried out at 55 °C. After equilibrium, the resin was collected on a glass filter and rinsed with 30 mL of ammonium acetate solution (pH 6.0) to reduce major elements such as Na, K, Mg, and Ca that had been partly adsorbed on the resin. Then, trace metals on the resin were eluted with 7.5 mL of 2 M nitric acid and collected in a 30 mL polypropylene bottle. In the second preconcentration step, the mixture of the filtrate and the rinsing solution obtained in the first step was adjusted to pH 4.0, and metal adsorption on another 0.4 g of Chelex-100 resin was carried out at 20 °C. In a similar manner to the first step, the resin collected on a glass filter was rinsed with 10 mL of ammonium acetate solution (pH 4.0), and trace metals adsorbed on the resin were eluted with 6 mL of 2 M nitric acid. This eluate was taken into the same polypropylene bottle as used in the first step. The final sample volume thus obtained was 15 mL including 1.5 mL of internal standard solution. Then a 33-fold preconcentration factor was achieved, where the recoveries for 33 elements were larger than 80%. The analytical results for trace metals in coastal seawater reference material (CASS-4) were in fairly good agreement with the certified or information values after correction with the recovery values. The coastal seawater samples from the Ise Bay and the Take Island were also analyzed by the present method. The concentrations for 20 trace metals in the Ise Bay coastal seawater were found to be more than 2-fold larger than those in the Take Island coastal seawater, indicating considerable anthropogenic pollution in the Ise Bay area.
Preparation of Methoxy-Substituted Optically Active 7-Alkoxycarbonylcycloheptatrienes and Their Acid-Promoted Rearrangements
Authors: Sugimura Takashi , Kagawa Masami , Ohuchi Naoko , Hagiya Kazutake , Okuyama Tadashi
Published: April 2005

Four optically active cycloheptatriene derivatives carrying a methoxy group(s) at different positions were prepared by the 2,4-pentanediol-tethered Büchner reaction. In addition to the high stereoselectivity, the tether also controlled the regioselectivity in a good-to-high degree. Some of the products are unstable under acidic conditions, resulting in isomerization through a prototropic reaction or aromatization. The Brønsted acid promoted prototropic isomerization by regio- and stereoselective protonation and ensuing deprotonation, while the Lewis acid-catalyzed reaction provided an aromatized product via the norcaradiene tautomer.
Design of Photofunctional Laminated Organized Thin Films: Photochromism of Ammoniumazobenzene Arenecarboxylates Cast on Silica Glass
Authors: Ohtani Osamu , Itoh Toshio , Monna Yuji , Sasai Ryo , Shichi Tetsuya , Yui Tatsuto , Takagi Katsuhiko
Published: April 2005

Arenecarboxylate counterions, i.e., benzoate (BA) and p-t-butylbenzoate (p-t-BBA), were observed to be effective in facilitating E-to-Z photoisomerizations in cast films of 1:1 ion-pair salts of cationic surfactant azobenzene (C8AzoC10N+). Such an effect of the arenecarboxylate ions in C8AzoC10N+ salts showed a contrast to untreated, as-prepared bromide salts, which exhibited no such activity. A remarkable E-to-Z photoisomerization was observed to take place with the cast films of C8AzoC10N+ salts involving bulky anions, BA (or p-t-BBA); their photochromic behavior corresponded well with the aggregated structures of the 1:1 ion-pair salts. Analyses of the π–A isothermal profiles, XRD, and UV–vis spectroscopic investigations showed that C8AzoC10N+-Br stacked films form densely packed interdigitated monolayers, whereas films of the C8AzoC10N+-salt with BA (or p-t-BBA) were found to form loosely packed monolayers.
Multimarker Quantitative Real-Time PCR Detection of Circulating Melanoma Cells in Peripheral Blood: Relation to Disease Stage in Melanoma Patients
Authors: Koyanagi Kazuo , Kuo Christine , Nakagawa Taku , Mori Takuji , Ueno Hideaki , Lorico Arnulfo R , Wang He-Jing , Hseuh Eddie , O’Day Steven J , Hoon Dave SB
Published: April 2005

Background: Detection of melanoma cells in circulation may be important in assessing tumor progression. The objective of this study was to develop a specific, reliable multimarker quantitative real-time reverse transcription-PCR (qRT) assay for detecting melanoma cells in patients’ blood.

Methods: We developed qRT assays for the mRNA of four melanoma-associated markers: MART-1, GalNAc-T, PAX-3, and MAGE-A3. In optimization studies, we tested 17 melanoma cell lines and 49 peripheral blood leukocyte (PBL) samples from volunteers. We performed RNA and melanoma cell dilution studies to assess the detection limits and imprecision of the assays. We measured the mRNAs in blood specimens from 94 melanoma patients [American Joint Committee on Cancer (AJCC) stage I, n = 20; II, n = 20; III, n = 32; IV, n = 22].

Results: All markers were frequently detected in melanoma cell lines, whereas none of the markers was detected in PBLs from volunteers. The qRT assay could detect 1 melanoma cell in 107 PBLs in the melanoma cell-dilution studies. Markers were detected in 15%, 30%, 75%, and 86% of melanoma patients with AJCC stage I, II, III, and IV disease, respectively. The number of positive markers and AJCC stage were significantly correlated (Spearman correlation coefficient = 0.58; P <0.0001).

Conclusions: Multimarker qRT can detect circulating melanoma cells in blood. Measurement of the studied molecular markers in blood may be useful in detection of metastasis and monitoring treatment response of melanoma patients.
Monitoring of Clopidogrel Action: Comparison of Methods
Authors: Geiger Jörg , Teichmann Lino , Grossmann Ralf , Aktas Barsom , Steigerwald Udo , Walter Ulrich , Schinzel Reinhard
Published: April 2005

Background: Clopidogrel is a potent drug for prevention of adverse effects during and after coronary intervention. Increasing experience indicates that a significant proportion of patients do not respond adequately to clopidogrel. Because failure of antiplatelet therapy can have severe consequences, there is need for a reliable assay to quantify the effectiveness of clopidogrel treatment.

Methods: Of 24 healthy volunteers admitted to the study, 18 were treated for 1 week with clopidogrel (300-mg loading dose and 75-mg maintenance dose), and 6 with placebo. Platelet function was monitored by 2 assays, based on flow cytometry and enzyme immunoassay, that measure the phosphorylation status of vasodilator-stimulated phosphoprotein (VASP) and by aggregometry, flow cytometry of P-selectin, and the platelet function analyzer at baseline, on days 1–5, and on day 9 of treatment.

Results: Aggregometry and VASP phosphorylation revealed a loss of platelet response to ADP within 12 h after clopidogrel intake. The phosphorylation status of VASP correlated with the inhibition of platelet aggregation. In contrast, neither P-selectin expression nor PFA-100 closure time was a clear indicator of clopidogrel effects on platelets.

Conclusions: VASP phosphorylation assays are reliable for quantifying clopidogrel effects. Because the VASP assay directly measures the function of the clopidogrel target, the P2Y12 receptor, the assay is selective for clopidogrel effects rather than effects of other platelet inhibitors commonly in use.
Community-Level Child Health: A Decade of Progress
Authors: Burton O. Marion
Published: April 2005

In the late 1980s, the leadership of the South Carolina Chapter of the American Academy of Pediatrics (AAP) developed a growing awareness that there was a population of children in the state who frequented emergency departments and public health clinics but were not considered patients in any medical professional's office. Coincidentally, the commissioner of the South Carolina Department of Health and Environmental Control was struggling to expand resources needed to care for these children, who were crowding his facilities in search of primary care. Department of Health and Environmental Control clinic staff increasingly were unable to provide core public health services because of the need to treat illnesses and conduct well-child visits.

Concurrently, with mounting concerns over the inadequacy and/or unavailability of quality health care for all children, the AAP embarked on the Access to Care campaign, a multiyear effort to improve access to care. The South Carolina Chapter of the AAP and Department of Health and Environmental Control subsequently launched an initiative, the Partnerships for Children program, to ensure that South Carolina children who were medically disenfranchised could have a medical home and all other services necessary for health and well-being. Although structured somewhat differently in various communities and practices, each of the >75 partnerships statewide focused on using public health professionals for specific care coordination and support that complemented physician office visits and encounters. These partnerships have gained substantial leverage through the expanding resources of the AAP Access to Care campaign.

In reviewing claims for children <3 years old who were enrolled in Medicaid before the establishment of the Partnerships for Children program, <45% had evidence of a well-child visit. Data in the fourth year of the program indicate that 84% of children in this age group have had at least 1 well-child visit. Other data suggesting improved access to care are equally reassuring.

In this report, I describe the evolution of the Partnerships for Children program, identify key ingredients for its success, and provide examples of effective strategies that bring community resources into pediatric practices to allow for more efficient and productive delivery of primary care. I also indicate the important role of the AAP Community Access to Child Health infrastructure in the maintenance and further development of this initiative.
Evidence-Based Community Pediatrics: Building a Bridge From Bedside to Neighborhood
Authors: Sanders Lee M. , Robinson Thomas N. , Forster Lourdes Q. , Plax Katie , Brosco Jeffrey P. , Brito Arturo
Published: April 2005

The American Academy of Pediatrics policy statement “The Pediatrician's Role in Community Pediatrics” encourages all pediatricians to partner with their communities to create and disseminate innovative programs that improve child health. This article describes 4 pillars of a bridge to evidence-based community pediatrics for pediatricians interested in pursuing effective community action: (1) collaborate with the community to establish a specific, short-term, health-related goal; (2) identify evidence-based best practice(s) for achieving the shared goal; (3) collaborate with the community to adapt this best practice to the community's unique assets and constraints; and (4) evaluate the project by using appropriate expertise. Practical elements of each pillar are described and illustrated by specific examples from community-based efforts of pediatricians and are accompanied by specific resources to aid pediatricians in their future community health work.
Teaching Community Pediatrics to Pediatric Residents: Strategic Approaches and Successful Models for Education in Community Health and Child Advocacy
Authors: Shipley Laura Jean , Stelzner Sarah M. , Zenni Elisa Alter , Hargunani Dana , O’Keefe Julie , Miller Carleen , Alverson Brian , Swigonski Nancy
Published: April 2005

To improve child health at a community level, pediatricians require knowledge and skills that have not been traditionally included in residency training. Recent policy statements from the American Academy of Pediatrics and requirements from Accreditation Council for Graduate Medical Education Residency Review committees emphasizing the importance of community pediatrics training have provided additional incentive for pediatric residency programs to actively explore methods of teaching the principles and promoting the practice of community pediatrics to resident trainees. With a growing number of diverse educational models in various stages of practice or development, common themes and approaches to promote successful teaching of community health and child advocacy can be described. This article defines strategies for 2 critical elements of community pediatrics training, engaging residents and building strong community partnerships, then highlights a number of educational models that illustrate key curricular components and methods. Published results from evaluations of some programs suggest that community pediatrics training of this caliber will cultivate a cadre of pediatricians (academic and community based, generalists and subspecialists, researchers and practitioners) who understand child health in the context of community and have the leadership and collaborative skills to improve the health of children in their communities.
The Essential Role of Research in Community Pediatrics
Authors: Duggan Anne , Jarvis James , Derauf D. Christian , Aligne C. Andrew , Kaczorowski Jeffrey
Published: April 2005

Several recommendations in the American Academy of Pediatrics policy statement “The Pediatrician's Role in Community Pediatrics” underscore the essential role of research as an agent of change to promote the health and well-being of children. This article provides (1) a framework for thinking about research in community pediatrics, (2) special considerations important in conducting community-level research, (3) an example of community-level research that has significantly decreased mortality in children (prevention of sudden infant death syndrome), (4) an example of a current issue illustrating the importance of community pediatrics research (promotion of school readiness), and (5) a discussion of future directions for research. Many of the leading health problems facing the United States as outlined in Healthy People 2010 are problems that affect children or have their roots in childhood and are likely to be addressed by community-level research and interventions. It seems clear that pediatricians should be learning to participate in, advocate for, and conduct more community pediatrics research.
Effects of Turbidity, Light Level, and Cover on Predation of White Sturgeon Larvae by Prickly Sculpins
Authors: Gadomski Dena M. , Parsley Michael J.
Published: April 2005

White sturgeon Acipenser transmontanus occur in rivers of the western United States and southwestern Canada, but some populations are in decline because of recruitment failure. Many river systems in this area have been altered as a result of development that has caused major environmental changes. Our goal was to examine how three changes—lower turbidity levels, higher light levels, and altered substrates—might affect predation by prickly sculpin Cottus asper on white sturgeon larvae. We experimentally investigated predation at various turbidity levels and found that significantly more white sturgeon yolk sac larvae were eaten at lower turbidity levels. The effects of light level (1–4 and 7–15 lx), the presence or absence of rocks as cover, and prey size (14–17 mm and 20–24 mm total length) on the outcome of predator–prey interactions were also examined. Significantly fewer white sturgeon were eaten during trials that combined the lowest light level, cover, and the smallest larvae. Our results suggest that altered river conditions caused by impoundment and other factors have increased predation on white sturgeon larvae.
Home Range and Space Use Patterns of Flathead Catfish during the Summer–Fall Period in Two Missouri Streams
Authors: Vokoun Jason C. , Rabeni Charles F.
Published: April 2005

Flathead catfish Pylodictis olivaris were radio‐tracked in the Grand River and Cuivre River, Missouri, from late July until they moved to overwintering habitats in late October. Fish moved within a definable area, and although occasional long‐distance movements occurred, the fish typically returned to the previously occupied area. Seasonal home range was calculated with the use of kernel density estimation, which can be interpreted as a probabilistic utilization distribution that documents the internal structure of the estimate by delineating portions of the range that was used a specified percentage of the time. A traditional linear range also was reported. Most flathead catfish (89%) had one 50% kernel‐estimated core area, whereas 11% of the fish split their time between two core areas. Core areas were typically in the middle of the 90% kernel‐estimated home range (58%), although several had core areas in upstream (26%) and downstream (16%) portions of the home range. Home‐range size did not differ based on river, sex, or size and was highly variable among individuals. The median 95% kernel estimate was 1,085 m (range, 70– 69,090 m) for all fish. The median 50% kernel‐estimated core area was 135 m (10–2,260 m). The median linear range was 3,510 m (150–50,400 m). Fish pairs with core areas in the same and neighboring pools had static joint space use values of up to 49% (area of intersection index), indicating substantial overlap and use of the same area. However, all fish pairs had low dynamic joint space use values (<0.07; coefficient of association), indicating that fish pairs were temporally segregated, rarely occurring in the same location at the same time.
Anti-proliferative effect of estrogen in breast cancer cells that re-express ERα is mediated by aberrant regulation of cell cycle genes
Authors: Moggs J G , Murphy T C , Lim F L , Moore D J , Stuckey R , Antrobus K , Kimber I , Orphanides G
Published: April 2005

Estrogen receptor (ER)-negative breast carcinomas do not respond to hormone therapy, making their effective treatment very difficult. The re-expression of ERα in ER-negative MDA-MB-231 breast cancer cells has been used as a model system, in which hormone-dependent responses can be restored. Paradoxically, in contrast to the mitogenic activity of 17β-estradiol (E2) in ER-positive breast cancer cells, E2 suppresses proliferation in ER-negative breast cancer cells in which ERα has been re-expressed. We have used global gene expression profiling to investigate the mechanism by which E2 suppresses proliferation in MDA-MB-231 cells that express ERα through adenoviral infection. We show that a number of genes known to promote cell proliferation and survival are repressed by E2 in these cells. These include genes encoding the anti-apoptosis factor SURVIVIN, positive cell cycle regulators (CDC2, CYCLIN B1, CYCLIN B2, CYCLIN G1, CHK1, BUB3, STK6, SKB1, CSE1 L) and chromosome replication proteins (MCM2, MCM3, FEN1, RRM2, TOP2A, RFC1). In parallel, E2-induced the expression of the negative cell cycle regulators KIP2 and QUIESCIN Q6, and the tumour-suppressor genes E-CADHERIN and NBL1. Strikingly, the expression of several of these genes is regulated in the opposite direction by E2 compared with their regulation in ER-positive MCF-7 cells. Together, these data suggest a mechanism for the E2-dependent suppression of proliferation in ER-negative breast cancer cells into which ERα has been reintroduced.
Ecological effects of pesticide use in the netherlands: Modeled and observed effects in the field ditch
Authors: de Zwart Dick
Published: April 2005

This study addresses the potential risks to the aquatic ecosystem posed by pesticides currently used in The Netherlands. The study used a novel method to predict aquatic exposure to pesticides based on a geographic information system (GIS) map of agricultural land use, comprising 51 crops used in open-canopy areas. Through the application of species-sensitivity distributions for aquatic organisms, in combination with rules for mixture-toxicity calculation, the modeled exposure results were transformed to risk estimates for aquatic species. The majority of the predicted risks were caused by pesticides applied to potato cropland, and approximately 95% of the predicted risk was caused by only 7 of the 261 pesticides currently used in The Netherlands. For risk verification, local toxic-risk estimates were compared with observed species composition in field ditches. The field verification study was not able to draw firm conclusions regarding the predicted impact of pesticide use on overall biodiversity. A toxicity-related shift from sensitive to more tolerant or opportunistic species could be observed for a few species.
On the boundary ergodic problem for fully nonlinear equations in bounded domains with general nonlinear Neumann boundary conditions
Authors: Da Lio Francesca , Barles Guy
Published: April 2005

We study nonlinear Neumann type boundary value problems related to ergodic phenomenas. The particularity of these problems is that the ergodic constant appears in the (possibly nonlinear) Neumann boundary conditions. We provide, for bounded domains, several results on the existence, uniqueness and properties of this ergodic constant.

Nous étudions des problèmes elliptiques non linéaires, associés à des conditions de Neumann, qui sont reliés à des phénomènes ergodiques. La particularité de ces problèmes vient du fait que la constante ergodique apparaît dans la condition de Neumann qui peut être non linéaire. Nous présentons, dans le cas de domaines bornés, plusieurs résultats sur l'existence, l'unicité et les propriétés de cette constante ergodique.
Transcriptional induction of Smurf2 ubiquitin ligase by TGF‐β
Authors: Ohashi Naro , Yamamoto Tatsuo , Uchida Chiharu , Togawa Akashi , Fukasawa Hirotaka , Fujigaki Yoshihide , Suzuki Sayuri , Kitagawa Kyoko , Hattori Takayuki , Oda Toshiaki , Hayashi Hidetoshi , Hishida Akira , Kitagawa Masatoshi
Published: April 2005

Smad ubiquitination regulatory factor 2 (Smurf2), a ubiquitin ligase for Smads, plays critical roles in the regulation of transforming growth factor‐β (TGF‐β)‐Smad signaling via ubiquitin‐dependent degradation of Smad2 and Smad7. We found that TGF‐β stimulates Smurf2 expression. TGF‐β activated the Smurf2 promoter in a TGF‐β responsive cell lines, whereas IL‐1α, PDGF and epidermal growth factor did not. TGF‐β‐mediated Smurf2 promoter activation was inhibited by Smad7 or an activin receptor‐like kinase 5 inhibitor but not by dominant negative Smad or disruption of Smad‐binding elements in the promoter. Moreover, inhibition of the phosphatidil inositol 3 kinase (PI3K)/Akt pathway suppressed TGF‐β‐mediated Smurf2 induction. These results suggest that TGF‐β stimulates Smurf2 expression by Smad‐independent pathway such as PI3K/Akt pathway via TGF‐β receptor.
Meningoencephalitis associated with passive immunization of a transgenic murine model of Alzheimer's amyloidosis
Authors: Lee Edward B. , Leng Lewis Z. , Lee Virginia M.-Y. , Trojanowski John Q.
Published: April 2005

Immunization against the Aβ peptide reverses the pathologic and behavioral manifestations of Alzheimer's disease in murine models. Since active immunization is associated with an autoimmune meningoencephalitis in a subset of humans, passive transfer of anti‐Aβ immunoglobulin is being pursued as a potentially safer alternative. We have identified cases of meningoencephalitis subsequent to peripheral and intracerebral passive immunization of Tg2576 mice. The vasocentric mononuclear infiltrate localized only to brain regions affected by Aβ amyloid deposits suggesting that the inflammatory reaction was Aβ specific. This report indicates that current passive immunization in humans should proceed with careful regard for autoimmune complications.
The interplay between structure and function in intrinsically unstructured proteins
Authors: Tompa Peter
Published: April 2005

Intrinsically unstructured proteins (IUPs) are common in various proteomes and occupy a unique structural and functional niche in which function is directly linked to structural disorder. The evidence that these proteins exist without a well‐defined folded structure in vitro is compelling, and justifies considering them a separate class within the protein world. In this paper, novel advances in the rapidly advancing field of IUPs are reviewed, with the major attention directed to the evidence of their unfolded character in vivo, the interplay of their residual structure and their various functional modes and the functional benefits their malleable structural state provides. Via all these details, it is demonstrated that in only a couple of years after its conception, the idea of protein disorder has already come of age and transformed our basic concepts of protein structure and function.
Roles of Mg2+ in TPP‐dependent riboswitch
Authors: Yamauchi Takahiro , Miyoshi Daisuke , Kubodera Takafumi , Nishimura Akira , Nakai Susumu , Sugimoto Naoki
Published: April 2005

We quantified the effect of Mg2+ on thiamine pyrophosphate (TPP) binding to TPP‐dependent thiA riboswitch RNA. The association constant of TPP binding to the riboswitch at 20 °C increased from 1.2 × 106 to 50 × 106
M−1 as the Mg2+ concentration increased from 0 to 1 mM. Furthermore, circular dichroic spectra under various conditions showed that 1 mM Mg2+ induced a local structural change of the riboswitch, which might be pivotal for TPP binding. These results indicate that a physiological concentration of Mg2+ can regulate TPP binding to the thiA riboswitch.
Induction of IGFBP‐1 expression by amino acid deprivation of HepG2 human hepatoma cells involves both a transcriptional activation and an mRNA stabilization due to its 3′UTR
Authors: Averous Julien , Maurin Anne-Catherine , Bruhat Alain , Jousse Céline , Arliguie Céline , Fafournoux Pierre
Published: April 2005

A dramatic overexpression of IGFBP‐1 is responsible for growth inhibition, in response to a low‐protein diet feeding. It has been demonstrated that a fall in the amino acid concentration was directly responsible for IGFBP‐1 induction. In this report, we sought to determine the mechanism by which amino acid limitation upregulates IGFBP‐1 expression. Our results show that both transcriptional activation and mRNA stabilization are involved. We also demonstrate that (i) the mGCN2/ATF4 pathway is not involved in this regulation and (ii) the 3′UTR of IGFBP‐1 mRNA is responsible for its destabilization and regulates its stability in response to amino acid starvation.
Sagittal Wrist Motion of Carpal Bones Following Intraarticular Fractures of the Distal Radius
Authors: LUTZ M. , RUDISCH A. , KRALINGER F. , SMEKAL V. , GOEBEL G. , GABL M. , PECHLANER S.
Published: April 2005

Forty patients (mean age, 37 years) with intraarticular C2 and C3 Colles fractures were treated by open reduction, internal fixation and bone grafting. At a mean follow-up of 8 years radiocarpal and midcarpal motion was evaluated, the depth of the articular surface of the distal radius in the sagittal plane was measured and the presence of arthritis was noted. The fractures healed with a mean palmar tilt of 6°, a mean ulnar tilt of 18° and ulna variance within 1 mm of the contralateral side. The depth of the articular surface of the distal radius was 1.3 mm greater than the uninvolved side. Measurement of carpal bone angles relative to the radius in maximum flexion and extension revealed lunate extension of 23°, lunate flexion of 15°, capitate extension of 62°, capitate flexion of 40°. There was a significant correlation between articular surface depth and radiocarpal motion.
Supplementary Core Sutures Increase Resistance to Gapping for Flexor Digitorum Profundus Tendon to Bone Surface Repair – An in vitro Biomechanical Analysis
Authors: KUSANO N. , ZAEGEL M. A. , PLACZEK J. D. , GELBERMAN R. H. , SILVA M. J.
Published: April 2005

We evaluated the effects of two types of supplementary core sutures on the tensile properties and resistance to gap formation of flexor digitorum profundus (FDP) tendon-bone repairs. Forty-five human cadaver FDP tendons were sharply released from their insertion sites and repaired to bone utilizing one of three repair techniques: four-strand modified Becker core suture (Becker only), modified Becker plus a figure-of-eight supplementary core suture (Becker plus figure-of-eight), and modified Becker plus a supplementary core suture using a bone anchor (Becker plus anchor). Ultimate (maximum) force did not differ between repair groups. However, addition of a supplementary suture significantly increased repair-site stiffness and the 1, 2 and 3 mm gap forces, while decreasing the gap at 20 N compared to the Becker only suture ( P<0.05). The only difference between the two supplementary suture groups was that the Becker plus anchor group had increased stiffness compared to the Becker plus figure-of-eight group. In conclusion, a supplementary figure-of-eight suture and a supplementary suture using a bone anchor provide enhanced resistance to gap formation for FDP tendon–bone repairs.
Identification of a Long-Chain Polyunsaturated Fatty Acid Acyl-Coenzyme A Synthetase from the Diatom Thalassiosira pseudonana
Authors: Tonon Thierry , Qing Renwei , Harvey David , Li Yi , Larson Tony Robert , Graham Ian Alexander
Published: April 2005

The draft genome of the diatom Thalassiosira pseudonana was searched for DNA sequences showing homology with long-chain acyl-coenzyme A synthetases (LACSs), since the corresponding enzyme may play a key role in the accumulation of health-beneficial polyunsaturated fatty acids (PUFAs) in triacylglycerol. Among the candidate genes identified, an open reading frame named TplacsA was found to be full length and constitutively expressed during cell cultivation. The predicted amino acid sequence of the corresponding protein, TpLACSA, exhibited typical features of acyl-coenzyme A (acyl-CoA) synthetases involved in the activation of long-chain fatty acids. Feeding experiments carried out in yeast (Saccharomyces cerevisiae) transformed with the algal gene showed that TpLACSA was able to activate a number of PUFAs, including eicosapentaenoic acid and docosahexaenoic acid (DHA). Determination of acyl-CoA synthetase activities by direct measurement of acyl-CoAs produced in the presence of different PUFA substrates showed that TpLACSA was most active toward DHA. Heterologous expression also revealed that TplacsA transformants were able to incorporate more DHA in triacylglycerols than the control yeast.