bluuebunny/crossref_metadata_2025 huggingface dataset:
Late cardiac evaluation of children with solid tumors after anthracycline chemotherapy
Authors: Güçlü Pınarlı F. , Oğuz Aynur , Sedef Tunaoğlu F. , Karadeniz Ceyda , Gökçora Nahide , Elbeg Şehri
Published: December 2004

Background

The therapeutic potential of anthracycline antibiotics is limited by their cardiotoxicity. Electrocardiography, exercise testing, and two‐dimensional echocardiography are non‐invasive techniques used in the follow‐up of children for cardiotoxicity. Plasma B‐type natriuretic peptide (BNP) levels are thought to be useful markers in the early detection of AC induced cardiomyopathy.

Procedure

We evaluated cardiac status of 34 patients with solid tumors treated with anthracycline antibiotics. All of the patients were asymptomatic and had no evidence of residual malignancy. They were evaluated by electrocardiography, exercise testing, echocardiography, and plasma BNP levels measured before and after the exercise testing.

Results

Electrocardiography revealed only minor abnormalities of little clinical significance. All of the patients completed the exercise testing without complication, and the duration of the exercise for each patient was between normal limits. Cardiac output (CO) and wall stress (WS) were significantly increased in patients, than in controls in echocardiographic evaluation of systolic functions (P < 0.001). Diastolic filling patterns showed various abnormalities; M‐E, M‐A, T‐E, T‐A, AT, and IVRT were significantly higher than those of controls. Mean plasma BNP levels of the patients (10.56 ± 10.22 pg/ml) were significantly higher than BNP levels of the healthy controls (4.09 ± 2.26 pg/ml) (P < 0.016), before exercise testing. The mean plasma BNP levels of the patients (15.70 ± 14.06 pg/ml) were higher than resting state after exercise testing, but it was not statistically significant (P > 0.05).

Conclusion

Our findings demonstrated that echocardiographic and biochemical abnormalities could be found even at low cumulative doses of AC antibiotics. The use of serial echocardiographic studies and plasma BNP determinations to identify high‐risk patients for cardiotoxicity needs to be verified by additional studies. © 2004 Wiley‐Liss, Inc.
Barriers to adherence of deferoxamine usage in sickle cell disease
Authors: Treadwell Marsha J. , Law Amy W. , Sung Jennifer , Hackney‐Stephens Ekua , Quirolo Keith , Murray Eileen , Glendenning G Alastair , Vichinsky Elliott
Published: December 2004

Background

We hypothesized that child cognitive disability would be a significant risk factor for non‐adherence with home deferoxamine (DFO) administration and that a factor that would contribute to improved adherence would be sharing of responsibilities for chelation between parents and patients. We explored the influences on adherence of behavioral and psychological adjustment; family stress; perceived convenience of and satisfaction with the DFO regimen; and parent and patient knowledge about DFO.

Procedure

Fifteen pediatric patients with sickle cell disease (SCD) who had evidence of excessive iron stores, and their parents, were interviewed about adherence and responsibility for chelation therapy. A neuropsychological assessment battery was administered to the patients. Family stress, the child's emotional and behavioral status, knowledge about chelation and iron overload were explored. Adherence was rated objectively using pharmacy refill patterns and observable signs of chelation.

Results

Sharing of responsibilities for chelation between parents and children was related to better adherence while neuropsychological status bore a complex relation to adherence. Of the exploratory variables, low family stress were related to better adherence while satisfaction with the home care regimen and convenience ratings were not useful in predicting adherence. No one element of adherence, even objective measures, was capable of classifying adherence, while a multifactorial scheme categorizing adherent, partially adherent and non‐adherent groups demonstrated good face validity.

Conclusions

Supporting developmentally appropriate sharing of responsibilities for self‐care is critical, taking patient neurocognitive status into consideration. Clinicians should evaluate adherence using a multifactorial model that highlights the most salient targets for intervention. © 2004 Wiley‐Liss, Inc.
Behavior of polyamidoamine dendrimers as curing agents in bis‐phenol A epoxy resin systems
Authors: Yiyun Cheng , Dazhu Chen , Rongqiang Fu , Pingsheng He
Published: December 2004

Polyamidoamine (PAMAM) dendrimers with different generations (0–5) were investigated as curing agents in epoxy resin systems. Flory's gelation theory and the Avrami equation were used to predict the cure behavior of epoxy resin/PAMAM/imidazole at various temperatures and PAMAM concentrations. The theoretical prediction is in good agreement with the experimental results obtained from the dynamic torsional vibration method. Copyright © 2004 Society of Chemical Industry
Impaired AP‐1 dimers and NFAT complex formation in immature thymocytes during in vivo glucocorticoid‐induced apoptosis
Authors: Wisniewska Marta , Pyrzynska Beata , Kaminska Bozena
Published: December 2004

Ca(2+)‐regulated nuclear factor of activated T cell (NFAT) family members are transcription factors crucial for the expression of various cytokine and other immunoregulatory genes. Moreover, NFAT transcription factors are involved in the regulation of development, maturation and selection of thymocytes. Typically, the NFAT complex is made up of NFATc (NFATc1‐4) protein and activator protein‐1 (AP‐1) transcription factor. AP‐1 is a dimer consisting of two Jun proteins (homodimers) or Jun and Fos proteins (heterodimers). We have previously reported that NFAT DNA‐binding activity significantly decreases in the thymus during glucocorticoid‐induced apoptosis. In this study, we demonstrate that the expression and phosphorylation status of the NFAT proteins do not change during glucocorticoid‐induced apoptosis. This suggests that glucocorticoids do not disturb a signal transduction pathway leading to the activation of NFATc proteins in thymocytes. Although the levels of particular Jun and Fos proteins do not decrease after glucocorticoid administration, the formation or DNA‐binding activity of some AP‐1 dimers is specifically abolished. Thus, the observed inhibition of NFAT transcription factor activity during glucocorticoid‐induced apoptosis is likely to be a consequence of this perturbation or the lack of a proper AP‐1 component.
Muscular myosin isoforms of Taenia solium (Cestoda)
Authors: Gonzalez‐Malerva Laura , Cruz‐Rivera Mayra , Reynoso‐Ducoing Olivia , Retamal Claudio , Flisser Ana , Ambrosio Javier R.
Published: December 2004

Type II myosin, the primary component of the thick filament of muscle fibers, is organized as a dimeric high molecular weight protein, and is composed of a pair of heavy chains (MHC) and two pairs of light chains. Myosin II transforms ATP energy into mechanical force. All type II myosins are conserved proteins but they have two variable regions that are located in different places of the molecule. Myosin molecules are encoded by a multigene family and many isoforms are generated. The expression of myosins depends on the developmental stage and on the type and degree of contractile activity and tissue, therefore several myosin isoforms are found in the same organism. Here we describe the use of different techniques that allowed demonstrating the presence of isoforms of the heavy chain type II myosin of Taenia solium cysticerci (larvae) and tapeworms (adults), a cestode parasite of importance in public health in many developing countries. Myosin was purified and used in comparative proteolytic fragmentation, ATPase activity, detection of antigenic differences and electrophoretic separation. The results obtained showed biochemical and immunochemical differences among cysticerci and tapeworms, and demonstrate the presence of myosin isoforms in T. solium that are probably associated to physiological requirements of each developmental stage.
Echo‐Doppler and clinical evaluations to define hemodynamic profile in patients with chronic heart failure: accuracy and influence on therapeutic management
Authors: Capomolla Soccorso , Ceresa Monica , Pinna GianDomenico , Maestri Roberto , La Rovere Maria Teresa , Febo Oreste , Rossi Angelo , Paganini Vincenzo , Caporotondi Angelo , Guazzotti Giampaolo , Gnemmi Marco , Mortara Andrea , Cobelli Franco
Published: December 2004

Background

Correct classification of chronic heart failure (CHF) patients by dual evidence of congestion and adequate perfusion is the primary clinical focus for management.

Objectives

To evaluate the accuracy of echo‐Doppler compared with clinical evaluation in determining the hemodynamic profile of patients with CHF; and to compare therapeutic changes based on hemodynamic or echo‐Doppler findings.

Methods

Three hundred and sixty‐six consecutive CHF patients (ejection fraction 25±7%) in sinus rhythm, undergoing evaluation for cardiac transplantation, underwent physical examination prior to right heart catheterization and echo‐Doppler studies. Subsequently, patients were randomized to therapeutic optimization using either right heart catheterization or echo‐Doppler data. The end‐points were: identification of low cardiac output (cardiac index <2.2 l/min/m2); high pulmonary wedge pressure (PWP >18 mm Hg); high right atrial pressure (RAP >5 mm Hg) and analysis of therapeutic changes made in response to the right heart catheterization and echo‐Doppler studies.

Results

Echo‐Doppler showed better accuracy in estimating abnormal hemodynamic indices than clinical variables (cardiac index <2.2 l/min/m2: echo positive predictive accuracy (PPA) 98% vs. clinical PPA 52% p<0.00001; PWP >18 mm Hg: echo PPA 85% vs. clinical PPA 76% p=0.0011; RAP >5 mm Hg: echo PPA 82% vs. clinical PPA 57% p<0.00001). When applied to individual patients, the echo‐Doppler assessment was more accurate than clinical evaluation in defining the different hemodynamic profiles: wet/cold (89% vs. 13%, p<0.0001); wet/warm (73% vs. 30%, p<0.0001); dry/cold (68% vs. 12%, p<0.0001); dry/warm (88% vs. 51%, p<0.0001). Therapeutic decision‐making based on echo‐Doppler findings was similar to that based on hemodynamics.

Conclusion

Echo‐Doppler hemodynamic monitoring proved accurate in estimating hemodynamic profiles and influenced therapeutic management.
Effect of valsartan added to background ACE inhibitor therapy in patients with heart failure: results from Val‐HeFT
Authors: Krum Henry , Carson Peter , Farsang Csaba , Maggioni Aldo P. , Glazer Robert D. , Aknay Nora , Chiang Yann‐Tong , Cohn Jay N.
Published: December 2004

Aims

To investigate the effect of valsartan in the Valsartan‐Heart Failure Trial (Val‐HeFT) when added to angiotensin‐converting enzyme inhibitor (ACEi) alone in patients with heart failure (HF).

Methods

Subjects in Val‐HeFT receiving ACEi but not beta‐blocker at baseline were analysed; 1532 were assigned to valsartan and 1502 assigned to placebo. Primary outcome events (all‐cause mortality, hospitalisation for adjudicated heart failure, sudden death with resuscitation and need for >4 h of parenteral therapy for worsening heart failure) were monitored.

Results

Mortality was not affected by valsartan but morbidity endpoints were significantly reduced (36.3% in placebo, 31.0% in valsartan, p=0.002) in patients receiving an ACEi but no beta‐blocker. Quality of life (QOL) was significantly improved, ejection fraction (EF) significantly increased, left ventricular (LV) diameter significantly reduced and plasma B‐type natriuretic peptide, norepinephrine and aldosterone levels significantly reduced with valsartan compared to placebo. The morbidity benefit was significant in patients on ACEi doses below the median (22% reduction, p=0.003) and not statistically significant in those receiving ACEi doses above the median (14% reduction, p=0.143).

Conclusion

Valsartan reduces heart failure hospitalisations and slows LV remodelling in patients treated with an ACEi in the absence of beta‐blockade, particularly in those on lower doses of ACEi.
Predictability of a favorable outcome in anorexia nervosa
Authors: Deter HC , Schellberg D. , Köpp W. , Friederich HC , Herzog W.
Published: December 2004

Objective

In a long-term follow-up of anorexia nervosa (AN) patients, somatic, psychological and social variables at clinical presentation should be investigated using a multilevel approach.

Methods

This study isolated predictors known from the literature over longer time periods and carried out a separate investigation of predictors in a sample of 81 AN patients of the Heidelberg–Mannheim study over a mean period of 12 years (range 9–19 years). Separate hierarchic regression analyses on the basis of the course of the Morgan–Russell categories were calculated for four individually recorded areas: anamnestic, psychological, somatic and social data sets.

Results

Age at the onset of the disease, purging behavior, low serum albumin, high glutamic-oxalo acetic transaminase (GOT) psychopathology (ANSS) and social pathology had the highest predictive value qualities. In survival analysis overall assessment of all six main predictors at clinical presentation could differentiate all patients who recovered from those who remained ill (log-rank test P = 0.019).

Conclusions

A small number of variables were important for detecting a good or poor long-term course of AN. At onset of the disease, it seems necessary to evaluate these psychological, somatic and social predictors.
Effect of a Suicide Prevention Centre for young people with suicidal behaviour in Copenhagen
Authors: Nordentoft M. , Branner J. , Drejer K. , Mejsholm B. , Hansen H. , Petersson B.
Published: December 2004

Background

In the 1980s, suicide rates in Denmark were among the highest in the world. In 1992, a Suicide Prevention Centre was opened in Copenhagen with a 2-week programme of social and psychological treatment. The aim of the study was to evaluate the effect of the Suicide Prevention Centre.

Methods

In a quasi-experimental study, 362 patients in the Suicide Prevention Centre and a parallel comparison group of 39 patients were interviewed with European Parasuicide Study Interviewer Schedule I (EPSIS I), which is a comprehensive interview including several validated scales. All patients were invited to follow-up interviews with EPSIS II and followed in the National Patients Register and the Cause of Death Register.

Results

At the 1-year follow-up, 59% of patients in the intervention group and 53% of patients in the comparison groups were interviewed with EPSIS II. The intervention group obtained a significantly greater improvement in Beck’s Depression Inventory, Hopelessness Scale, Rosenberg’s Self-Esteem Scale and CAGE-score and a significantly lower repetition rate.

Discussions

Although the design cannot exclude selection bias, it seems likely that the improvement in the intervention group was facilitated by the treatment.
An association study between polymorphisms in five genes in glutamate and GABA pathway and paranoid schizophrenia
Authors: Zhang Boyu , Yuan Yanbo , Jia Yanbin , Yu Xin , Xu Qi , Shen Yucun , Shen Yan
Published: December 2004

Dysfunctions of glutamatergic and GABAergic neurotransmission are two important hypotheses for the pathogenesis of schizophrenia. Thus, genes in the pathway are candidates for schizophrenia susceptibility. Phosphate-activated glutaminase (GLS), glutamine synthetase (GLUL), glutamic acid decarboxylase (GAD), GABA transaminase (ABAT) and succinic semialdehyde dehydrogenase (ALDH5A1) are five primary enzymes in glutamate and GABA synthetic and degradative pathway. In order to investigate the possible involvement of these genes in the development of paranoid schizophrenia, we genotyped 80 paranoid schizophrenics from northern China and 108 matched controls by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) methods or directly sequencing of PCR product. Seven SNPs were found to be polymorphic in the population investigated. No significant differences in the genotype distributions or allele frequencies between patients and controls were found. Therefore, we conclude the polymorphisms studied in the five genes do not play major roles in pathogenesis of paranoid schizophrenia in the population investigated.
Effects of Yoku-kan-san on undifferentiated somatoform disorder with tinnitus
Authors: Okamoto Hideki , Okami Toshihiko , Ikeda Masatoshi , Takeuchi Tatsuo
Published: December 2004

Up to the present, there have been few strategies that are completely effective in treating undifferentiated somatoform disorder with tinnitus. We herein report that Yoku-kan-san (TJ-54), one of Japan's traditional herbal medicines, is an effective treatment for tinnitus in undifferentiated somatoform disorder complicated with headache and insomnia. TJ-54 has been also used as an effective treatment for insomnia and irritability in recent centuries and is considered to have some effects on the excitability of nerves. Further studies are needed to confirm the efficacies of Japanese herbal medicines.
Old versus new: weighing the evidence between the first- and second-generation antipsychotics
Authors: Davis John M. , Chen Nancy
Published: December 2004

In our opinion the best guide to prescribing antipsychotics is the clinician’s experience with his patients and in particular the patient being treated. If treatment works, stick with it. We feel it is also important for the clinician to consider the evidence from well-controlled double-blind random-assignment studies because in “evidence-based medicine,” biases both known and unknown are controlled by blinding and randomization. The purpose of this paper is to summarize and discuss the evidence on efficacy. Choice of antipsychotic, in our opinion, is probably the most important decision that the clinician makes for the psychotic patient. This involves the choice of drug, its dose, balancing efficacy, side-effects and cost.
Structural modeling of dual‐affinity purified Pho84 phosphate transporter
Authors: Lagerstedt Jens O. , Voss John C. , Wieslander Åke , Persson Bengt L.
Published: December 2004

The phosphate transporter Pho84 of Saccharomyces cerevisiae is predicted to contain 12 transmembrane (TM) regions, divided into two partially duplicated parts of 6 TM segments. The three‐dimensional (3D) organization of the Pho84 protein has not yet been determined. However, the 3D crystal structure of the Escherichia coli MFS glycerol‐3‐phosphate/phosphate antiporter, GlpT, and lactose transporter, LacY, has recently been determined. On the basis of extensive prediction and fold recognition analyses (at the MetaServer), GlpT was proposed as the best structural template on which the arrangement of TM segments of the Pho84 transporter was fit, using the comparative structural modeling program MODELLER. To initiate an evaluation of the appropriateness of the Pho84 model, we have performed two direct tests by targeting spin labels to putative TM segments 8 and 12. Electron paramagnetic resonance spectroscopy was then applied on purified and spin labeled Pho84. The line shape from labels located at both positions is consistent with the structural environment predicted by the template‐generated model, thus supporting the model.
Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV‐1 genome dimerization and inhibit virus replication
Authors: Elmén Joacim , Zhang Hong-Yan , Zuber Bartek , Ljungberg Karl , Wahren Britta , Wahlestedt Claes , Liang Zicai
Published: December 2004

We have evaluated antisense design and efficacy of locked nucleic acid (LNA) and DNA oligonucleotide (ON) mix‐mers targeting the conserved HIV‐1 dimerization initiation site (DIS). LNA is a high affinity nucleotide analog, nuclease resistant and elicits minimal toxicity. We show that inclusion of LNA bases in antisense ONs augments the interference of HIV‐1 genome dimerization. We also demonstrate the concomitant RNase H activation by six consecutive DNA bases in an LNA/DNA mix‐mer. We show ON uptake via receptor‐mediated transfection of a human T‐cell line in which the mix‐mers subsequently inhibit replication of a clinical HIV‐1 isolate. Thus, the technique of LNA/DNA mix‐mer antisense ONs targeting the conserved HIV‐1 DIS region may provide a strategy to prevent HIV‐1 assembly in the clinic.
Learning module networks from genome‐wide location and expression data
Authors: Xu Xiaojiang , Wang Lianshui , Ding Dafu
Published: December 2004

We develop a systematic algorithm for discovering network of regulatory modules, which identifies regulatory modules and their regulation program by integrating genome‐wide location and expression data. Unlike previous approaches [Eisen, M.B., Spellman, P.T., Brown, P.O. and Botstein, D. (1998) Proc. Natl. Acad. Sci. USA 95, 14863–14868; Tavazoie, S., Hughes, J.D., Campbell, M.J., Cho, R.J. and Church, G.M. (1999) Nat. Genet. 22, 281–285; Ihmels, J., Friedlander, G., Bergmann, S., Sarig, O., Ziv, Y. and Barkai, N. (2002) Nat. Genet. 31, 370–377; Segal, E., Shapira, M., Regev, A., Pe'er, D., Botstein, D., Koller, D. and Friedman, N. (2003) Nat. Genet. 34, 166–176] that relied primarily on gene expression data, our algorithm regards the regulator binding data as prior knowledge that provide direct evidence of physical regulatory interactions. We applied the method to aSaccharomyces cerevisiaegenome‐wide location data [Lee, T.I., Rinaldi, N.J., Robert, F., Odom, D.T., Bar‐Joseph, Z., Gerber, G.K., Hannett, N.M., Harbison, C.T., Thompson, C.M., Simon, I., Zeitlinger, J., Jennings, E.G., Murray, H.L. Gordon, D.B., Ren, B., Wyrick, J.J., Tagne, J.B., Volkert, T.L., Fraenkel, E., Gifford, D.K. and Young, R.A. (2002) Science 298, 799–804] for 106 DNA‐binding transcription factors and 250 gene expression experiments under the conditions from the cell cycle to responses to various stress conditions. The results show that our method is able to identify functionally coherent modules and their proper regulators. Supplementary materials are available athttp://compbio.sibsnet.org/projects/module‐network/.
Regulation of tau exon 10 splicing by a double stem–loop structure in mouse intron 10
Authors: Yamashita Takenari , Tomiyama Takami , Li Qiang , Numata Hideharu , Mori Hiroshi
Published: December 2004

Tau exon 10 (E10) splicing is a crucial event in its developmental change of tau isoform and tauopathy. To investigate the splicing mechanism, we isolated and compared mouse tau genomic sequence with human sequence. We identified a new element in mouse intron 10 (I10) to suppress E10 splicing, which was located just after the stem–loop region previously proposed in human sequence and found to potentially form another stem–loop. Human I10 with a mutation (+29G to A) causing a decreased E10 splicing was also predicted to form similar double stem–loop, suggesting that this element is universally involved in regulation of E10 splicing.
2‐Aminoperimidine, a specific inhibitor of bacterial NhaA Na+/H+ antiporters
Authors: Dibrov Pavel , Rimon Abraham , Dzioba Judith , Winogrodzki Arthur , Shalitin Yechiel , Padan Etana
Published: December 2004

The diuretic drug amiloride and its numerous derivatives are competitive inhibitors of mammalian Na+/H+ antiporters and other eukaryotic antiporters. Most prokaryotic antiporters, including the major NhaA family of enterobacteria, are resistant to these compounds. We show that 2‐aminoperimidine (AP), a guanidine‐containing naphthalene derivative with some similarity to amiloride, acts as a specific inhibitor of NhaA from Escherichia coli. Similar concentrations (IC50 of 0.9 μM) inhibit the proton motive force dependent Na+(Li+)/H+ exchange reaction in inside‐out sub‐bacterial vesicles (at 10 mM NaCl, pH 8) as well as the initial rate of 22Na+/Na+ exchange mediated by pure NhaA in proteoliposomes. The inhibitor is specific to NhaA type antiporters, so AP is a new tool to study the mechanism and roles of NhaA antiporters of enterobacteria as well as the molecular basis of inhibition by an amiloride‐like compound.
Age and individual growth of Mesodesma mactroides (Bivalvia) in the southernmost range of its distribution
Authors: Fiori Sandra M. , Morsán Enrique M.
Published: December 2004

The yellow clam, Mesodesma mactroides, is an intertidal bivalve typical from sandy beaches of the South American Atlantic coast. Growth parameters of southernmost populations of M. mactroides were studied and compared with other populations. Thin shell sections were examined to describe internal shell layers and to contrast with external shell transparency. Periodicity of deposition of external growth increments was studied recording the degree of transparency of the shell border. Growth patterns were determined using modal progression analysis from size frequency distributions, analysis of external shell increments, and size-at-age data derived from inner shell layers. Growth parameters were described using the von Bertalanffy growth model. Both internal and external patterns were coincident and exhibited a succession of one translucent and one opaque region. The transparent region was deposited during summer. Growth differences found between populations may be related to unequal size of first ring in both beaches. This feature may originate from asynchrony in spawning and recruitment. The monthly analysis of shell length size frequency distribution shows that growth of M. mactroides is seasonal. Estimations of asymptotic size of studied populations and others located at the southern (coldest) half of the geographical range of distribution suggest a negative relation with latitude.
Diel vertical migration and shoaling heterogeneity in Atlantic redfish: effects on acoustic and bottom-trawl surveys
Authors: Gauthier Stéphane , Rose George A.
Published: December 2004

A series of experiments comparing acoustic and bottom-trawl surveys was conducted on Atlantic redfish (Sebastes spp.) on the edge of the Green and Grand Banks of Newfoundland, Canada. Redfish were on or near bottom by day and migrated vertically in the water column at night. In an attempt to account for biases attributable to the presence of fish in the near-bottom dead zone (DZ), a correction factor was applied based on density values measured within the first few metres above the detected bottom. Acoustic densities within increasing range increments above the bottom were compared with densities estimated from the trawl catch. Swept area was calculated using both the trawl's wing spread and door spread as proxies for the minimum and maximum fishing widths. Uncorrected acoustic densities were significantly higher during the night than during the day. No significant day/night differences for the entire water column were observed after DZ corrections. Close agreement between acoustic and trawl densities was obtained by integrating within the first 10 to 20 m off the bottom, with or without the DZ corrections, for both day and night experiments, but regression slopes differed. Trawl catchability appeared to be density-dependent at night, being higher at lower fish densities. Daytime acoustic estimates were more variable than those made at night, as indicated by consecutive passes of several transects and CVs of density (means of 131% during day, 35% at night). We conclude that acoustic measurements made at night provide the most reliable and least variable density estimates, and make recommendations for surveys.
A Comparison of Fusion, Trapeziectomy and Silastic Replacement for the Treatment of Osteoarthritis of the Trapeziometacarpal Joint
Authors: TAYLOR E. J. , DESARI K. , D’ARCY J. C. , BONNICI A. V.
Published: December 2004

This retrospective study compares three of surgical treatments for osteoarthritis of the trapeziometacarpal joint of the thumb. We assessed the outcomes of a total of 83 operations at a follow-up of between 1 and 5 years. The types of treatment were, fusion of the carpometacarpal joint (36 operations), excision of the trapezium with or without a sling ligament reconstruction (25 operations), and silastic trapezial replacement (22 operations). Assessments included patient satisfaction, pain measurement, range of movement, tip and key pinch, and complication rates. There were no significant differences between the clinical outcome of the treatments, though there was higher rate of complications and reoperation in the fusion group.
Bilateral Kienböck’s Disease
Authors: YAZAKI N. , NAKAMURA R. , NAKAO E. , IWATA Y. , TATEBE M. , HATTORI T.
Published: December 2004

We conducted a retrospective review of 11 patients with bilateral Kienböck’s disease from our series of 251 patients with Kienböck’s disease. There were no significant differences in radiographic parameters, including ulnar variance and carpal bone angle, between those with unilateral and those with bilateral Kienböck’s disease. None of the patients with bilateral disease had been treated with corticosteroids or had a systemic disease that predisposed to osteonecrosis. Thus, this study failed to demonstrate any risk factor for bilateral, as opposed to unilateral Kienböck’s disease.
Trial Pinning Prior to Wrist Arthrodesis in Children
Authors: GOLDFARB C. A. , YEN A. Y. , MANSKE P. R.
Published: December 2004

The purpose of this investigation was to assess the utility of trial wrist pinning as an assessment tool prior to wrist arthrodesis in the paediatric patient. Ten paediatric patients who were unable to decide if a wrist arthrodesis would be beneficial to them underwent a trial wrist pinning (using temporary K-wires) in neutral posture for an average of 28 days. The etiology of wrist pathology varied. The utility of the trial pining in decision-making was assessed through chart review and telephone conversation.

All patients felt the trial pinning facilitated their decision. Two of the 10 patients declined wrist arthrodesis secondary to difficulty with daily activities. Eight patients who underwent wrist arthrodesis were satisfied with wrist position and function. Temporary wrist pinning is an effective informational tool for patients, families and physicians, allowing a true assessment of wrist function prior to definitive wrist arthrodesis.
Testing claims about volcanic disruption of a potential geologic repository at Yucca Mountain, Nevada
Authors: Coleman N. M. , Abramson L. R. , Marsh B. D.
Published: December 2004

Yucca Mountain is a potential repository site for high‐level radioactive waste. We examine claims that the frequency of future basaltic dike intersection could be 1 × 10−6/yr or higher (i.e., on average, one penetration every million yrs). These claims fail simple tests at four time scales. Spatial‐temporal models that predict intrusion frequencies >2 × 10−7/yr are overly pessimistic because no dikes have been found in the 13 Myr‐old potential repository footprint. More realistic models are developed by considering this non‐detection of dikes and by applying probabilistic hazard assessments based on known patterns of Pleistocene volcanism. Using a hazard assessment code, we estimate the frequency of dike intersection at 5.4 × 10−8/yr with an upper 95% confidence bound of 9.8 × 10−8/yr.
Water‐worked gravel surfaces: High‐order structure functions at the particle scale
Authors: Nikora Vladimir , Walsh Jeremy
Published: December 2004

High‐order structure functions are applied at the particle scale for studying water‐worked gravel surfaces measured at several field sites in New Zealand. The key findings relate to the shape of the two‐dimensional structure functions and their scaling behavior. The data suggest that at scales comparable to d50 the topography of gravel surfaces is sensitive to the flow direction and exhibits multiscaling behavior. We postulate, based on our analysis and physical considerations, that the high‐order structure functions may provide information on the orientation and direction of the flow that formed the surface.
Development of a focused charged particle microbeam for the irradiation of individual cells
Authors: Barberet Ph. , Balana A. , Incerti S. , Michelet-Habchi C. , Moretto Ph. , Pouthier Th.
Published: December 2004

An irradiation facility, able to expose cellular and subcellular targets to a precise number of particles, has been developed at CENBG for applications in radiobiology. The development of this facility was based on an existing horizontal focused microbeam developed in the early 90’s for material analysis. The focusing properties of the line allow the delivering of proton or alpha particle beams in the 1–3.5MeV energy range with a spatial resolution down to about 1μm under vacuum. For irradiation of living cells, a removable stage has been developed to extract the beam into air while preserving the analytical capabilities of the microbeam line under vacuum. This stage includes a high resolution epifluorescence microscope for online visualization of the cells and a motorized stage for cell positioning. Single particle control is ensured by a fast electrostatic deflector triggered by the signal induced by the particles through a transmission detector just before reaching the target. A dedicated software, based on an object-oriented architecture, has been designed to control the entire experiment. This includes semiautomatic calibration procedures (necessary to achieve the micron precision) and semiautomatic irradiation procedures used for targeting a large number of individual cells. In air irradiation of solid track detectors has permitted us to estimate that 99.5% of the particles are delivered on the target at a distance lower than 5μm from the beam center when an alpha particles beam is used. The targeting precision of the overall irradiation procedure, which reflects the alignment precision of the beam center with the target center, has been estimated to be within ±2μm. First experiments involving cells in culture have permitted to estimate an irradiation rate of 2000 cells per hour. This article presents the overall experimental facility and the tests performed for its validation for the irradiation of individual cells in their culture medium.
Low energy beam line at the AGOR facility
Authors: Toprek Dragan , Formanoy Iwo , Brandenburg Sytze
Published: December 2004

The origin of the low transmission through the low energy beam line between the electron cyclotron resonance source and the AGOR cyclotron has been investigated. Measurements of beam size and emittance, determined with the “varying quadrupole method,” are compared with calculations including fringe fields up to third order with the code COSY INFINITY. Calculations and measurements qualitatively agree; the calculations exhibit the large beam losses observed. On the basis of the calculations new settings have been determined, resulting in a significant increase of the transmission. To achieve full transmission a complete redesign of the beam line, in particular of the bending magnets, is needed.
Sir Thomas Brisbane's Legacy to Colonial Science: Colonial Astronomy at the Parramatta Observatory, 1822 - 1848
Authors: Saunders Shirley D.
Published: December 2004

Sir Thomas Makdougall Brisbane's legacy to colonial science derives from his initiative in establishing a privately owned observatory in the southern hemisphere, the Parramatta Observatory, during his term as Governor of the Colony of New South Wales from 1822 to 1825. In this paper a discussion is given of the origin and setting up of Brisbane's Parramatta Observatory, including the recruitment and employment of Carl Rümker and James Dunlop. An account is given of the choice of the work undertaken at Parramatta Observatory when it was privately owned by Brisbane such as the rediscovery of Encke's Comet in 1822, the publication of a catalogue of 7,385 southern stars in 1835 and measurements of earthly phenomena such as the weather, the temperature of the interior of the Earth and the figure of the Earth. An investigation is made of the ensuing struggles as the Parramatta Observatory moved from a private, gentlemanly endeavour to a more accountable public-sector institution in a distant colony of Britain. The main events concerning the public Parramatta Observatory are chronicled from 1826 to 1830 during the years when Rümker worked at the Observatory. A discussion is given of the period 1831 to 1848 at the Parramatta Observatory during Dunlop's term of public office, concluding with an account of the decay and demolition of the observatory.
Who gets acknowledged: Measuring scientific contributions through automatic acknowledgment indexing
Authors: Giles C. Lee , Councill Isaac G.
Published: December 2004

Acknowledgments in research publications, like citations, indicate influential contributions to scientific work. However, acknowledgments are different from citations; whereas citations are formal expressions of debt, acknowledgments are arguably more personal, singular, or private expressions of appreciation and contribution. Furthermore, many sources of research funding expect researchers to acknowledge any support that contributed to the published work. Just as citation indexing proved to be an important tool for evaluating research contributions, we argue that acknowledgments can be considered as a metric parallel to citations in the academic audit process. We have developed automated methods for acknowledgment extraction and analysis and show that combining acknowledgment analysis with citation indexing yields a measurable impact of the efficacy of various individuals as well as government, corporate, and university sponsors of scientific work.
Activation of liver X receptors and retinoid X receptors prevents bacterial-induced macrophage apoptosis
Authors: Valledor Annabel F. , Hsu Li-Chung , Ogawa Sumito , Sawka-Verhelle Dominique , Karin Michael , Glass Christopher K.
Published: December 2004

Microbe-macrophage interactions play a central role in the pathogenesis of many infections. The ability of some bacterial pathogens to induce macrophage apoptosis has been suggested to contribute to their ability to elude innate immune responses and successfully colonize the host. Here, we provide evidence that activation of liver X receptors (LXRs) and retinoid X receptors (RXRs) inhibits apoptotic responses of macrophages to macrophage colony-stimulating factor (M-CSF) withdrawal and several inducers of apoptosis. In addition, combined activation of LXR and RXR protected macrophages from apoptosis caused by infection withBacillus anthracis, Escherichia coli, andSalmonella typhimurium. Expression-profiling studies demonstrated that LXR and RXR agonists induced the expression of antiapoptotic regulators, including AIM/CT2, Bcl-XL, and Birc1a. Conversely, LXR and RXR agonists inhibited expression of proapoptotic regulators and effectors, including caspases 1, 4/11, 7, and 12; Fas ligand; and Dnase1l3. The combination of LXR and RXR agonists was more effective than either agonist alone at inhibiting apoptosis in response to various inducers of apoptosis, and it acted synergistically to induce expression of AIM/CT2. Inhibition of AIM/CT2 expression in response to LXR/RXR agonists partially reversed their antiapoptotic effects. These findings reveal unexpected roles of LXRs and RXRs in the control of macrophage survival and raise the possibility that LXR/RXR agonists may be exploited to enhance innate immunity to bacterial pathogens that induce apoptotic programs as a strategy for evading host responses.
Tumor imaging by means of proteolytic activation of cell-penetrating peptides
Authors: Jiang Tao , Olson Emilia S. , Nguyen Quyen T. , Roy Melinda , Jennings Patricia A. , Tsien Roger Y.
Published: December 2004

We have devised and tested a new strategy for selectively delivering molecules to tumor cells. Cellular association of polyarginine-based, cell-penetrating peptides (CPPs) is effectively blocked when they are fused to an inhibitory domain made up of negatively charged residues. We call these fusions activatable CPPs (ACPPs) because cleavage of the linker between the polycationic and polyanionic domains, typically by a protease, releases the CPP portion and its attached cargo to bind to and enter cells. Association with cultured cells typically increases 10-fold or more upon linker cleavage. In mice xenografted with human tumor cells secreting matrix metalloproteinases 2 and 9, ACPPs bearing a far-red-fluorescent cargo showin vivocontrast ratios of 2-3 and a 3.1-fold increase in standard uptake value for tumors relative to contralateral normal tissue or control peptides with scrambled linkers.Ex vivoslices of freshly resected human squamous cell carcinomas give similar or better contrast ratios. Because CPPs are known to import a wide variety of nonoptical contrast and therapeutic agents, ACPPs offer a general strategy toward imaging and treating disease processes associated with linker-cleaving activities such as extracellular proteases.
Microstimulation of the superior colliculus focuses attention without moving the eyes
Authors: Müller James R. , Philiastides Marios G. , Newsome William T.
Published: December 2004

The superior colliculus (SC) is part of a network of brain areas that directs saccadic eye movements, overtly shifting both gaze and attention from position to position, in space. Here, we seek direct evidence that the SC also contributes to the control of covert spatial attention, a process that focuses attention on a region of space different from the point of gaze. While requiring monkeys to keep their gaze fixed, we tested whether microstimulation of a specific location in the SC spatial map would enhance visual performance at the corresponding region of space, a diagnostic measure of covert attention. We find that microstimulation improves performance in a spatially selective manner: thresholds decrease at the location in visual space represented by the stimulated SC site, but not at a control location in the opposite hemifield. Our data provide direct evidence that the SC contributes to the control of covert spatial attention.
The FIP3-Rab11 Protein Complex Regulates Recycling Endosome Targeting to the Cleavage Furrow during Late Cytokinesis
Authors: Wilson Gayle M. , Fielding Andrew B. , Simon Glenn C. , Yu Xinzi , Andrews Paul D. , Hames Rebecca S. , Frey Andrew M. , Peden Andrew A. , Gould Gwyn W. , Prekeris Rytis
Published: December 2004

An integral part of cell division is the separation of daughter cells via cytokinesis. There is now good evidence that the completion of cytokinesis requires coordinated membrane trafficking to deliver new membrane to the tip of the furrow and to complete the abscission. Here we have examined membrane traffic in cytokinesis and describe several novel observations. First, we show that Rab11- and FIP3-containing recycling endosomes accumulate near the cleavage furrow and are required for successful completion of cytokinesis. Second, we demonstrate that the Rab11-FIP3 protein complex is intimately involved in the delivery of endosomes to the cleavage furrow. Significantly, although FIP3 recruitment to endosomes is Rab11 dependent, we find that the targeting of FIP3 to the midbody is independent of Rab11. Third, we show that the Rab11-FIP3 complex is required for a late stage of cytokinesis, possibly abscission. Finally, we demonstrate that localization of FIP3 is subject to substantial spatial and temporal regulation. These data provide the first detailed analysis of recycling endosomes in cell division and provide a new model for membrane traffic to the furrow. We propose that the dynamic Rab11-FIP3 interaction controls the delivery, targeting, and fusion of recycling endosomes with furrow during late cytokinesis and abscission.
Role of the GABA‐A System in Estrogen‐Induced Protection Against Brain Lipid Peroxidation in Ethanol‐Withdrawn Rats
Authors: Rewal Mridula , Jung Marianna E. , Simpkins James W.
Published: December 2004

Background:Our previous study showed that 17 β‐estradiol (E2) treatment protects against cerebellar neuronal death and related motor deficits in ethanol‐withdrawn rats, in part through the GABAergic system. In this study, we examined the effect of the GABA‐A antagonist bicuculline on the neuroprotective effect of E2 by assessing the oxidative marker thiobarbituric acid reactive substances (TBARS) during ethanol withdrawal (EW).

Methods:Ovariectomized animals that had implants of E2 (EW/E2) or oil (EW/Oil) pellets received liquid ethanol (7.5% w/v) or dextrin for 7 days by gavage. The GABA‐A antagonist bicuculline (1.25 mg/kg) was administered (three times a day intraperitoneally) for 4 days starting 3 days before the onset of EW. After testing for overt EW signs at 7 hr of EW, one set of the animals was immediately killed for the collection of the cerebellum, hippocampus, and cortex. The brain homogenates were further processed for TBARS assay to detect TBARS in the presence or absence of FeCl3. For assessing motor capacity, the other set of animals was tested for the latency to fall from a rotarod after 1 week of EW.

Results:The EW/Oil animals had enhanced endogenous and FeCl3‐stimulated TBARS levels in the cerebellum and the hippocampus in a manner potentiated by bicuculline but inhibited by E2. Bicuculline counteracted the protective effect of E2 when administered along with E2. Pearson correlation coefficients indicated that the latency to fall from the rotarod covaried with TBARS levels in the cerebellum and the hippocampus.

Conclusion:These data suggest that E2 protects against lipid peroxidation in vulnerable brain areas of ethanol‐withdrawn rats, in part through the GABAergic system.
Motor Impairing Effects of Ethanol and Diazepam in Rats Selectively Bred for High and Low Ethanol Consumption in a Limited‐Access Paradigm
Authors: Shram Megan J. , Bahroos Manisha , Beleskey Jeff I. , Tampakeras Maria , Lê Anh D. , Tomkins Denise M.
Published: December 2004

Background: Some clinical studies suggest that an initial low‐level response in ethanol sensitivity is a good predictor of risk for developing subsequent high levels of ethanol consumption in humans; however, there are some inconsistencies in the data. In experimental research, this association between low ethanol sensitivity and high ethanol intake has not been consistently reported in studies that have used rat lines that have been genetically selected for differences in ethanol intake under continuous access conditions (e.g., UChA versus UchB, P versus NP, AA versus ANA). The present study investigated ethanol sensitivity in high (HARF) and low (LARF) ethanol‐preferring rats selectively bred under limited‐access conditions. For comparative purposes, motor impairment induced by diazepam was also examined.

Methods: Motor impairment was assessed using the tilt plane. Ethanol (1.25, 2.0, and 2.5 g/kg, intraperitoneally) was administered to ethanol‐naïve male and female HARF and LARF rats, and their performance was assessed at t= 0, 30, and 60 min. Blood ethanol levels were measured in a separate group of ethanol‐naïve rats. Finally, in a separate group of male and female HARF and LARF rats, diazepam‐induced (1, 3, and 10 mg/kg, intraperitoneally) motor impairments were evaluated in a similar manner.

Results: In the ethanol study, HARF rats showed greater dose‐dependent impairments than their LARF counterparts. Male rats exhibited greater sensitivity to ethanol‐induced impairment than their female counterparts. These observations were unrelated to sex or line differences in the blood ethanol levels achieved. Similar impairments were observed with diazepam, with HARF rats exhibiting greater motor impairment than LARF rats.

Conclusions: The results suggest that selective breeding for high and low ethanol drinking in a limited‐access paradigm has led to inherent differences in sensitivity to ethanol‐ and diazepam‐induced motor impairments. The pattern of diazepam‐induced impairments suggests possible variations in GABAA receptor activity, although more research is necessary to determine such involvement.