bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smooth pursuit deficits in schizophrenia, affective disorder and obsessive–compulsive disorder
Authors: LENCER R. , TRILLENBERG P. , TRILLENBERG-KRECKER K. , JUNGHANNS K. , KORDON A. , BROOCKS A. , HOHAGEN F. , HEIDE W. , AROLT V. 
Published: March 2004

Background. In schizophrenia, affective disorders, and obsessive–compulsive disorder (OCD) dysfunction of frontal neuronal circuits has been suggested. Such impairments imply corresponding oculomotor deficits.Method. Eye movement response to foveofugal and foveopetal step–ramp stimuli was recorded within the same study design in patients with schizophrenia (N=16), affective disorder (N=15), and OCD (N=18) and compared with controls (N=23) using infra-red reflection oculography.Results. In the foveofugal task steady-state velocity was lower in all patient groups compared with controls. Post-saccadic eye velocity was also decreased in patients with schizophrenia and affective disorder. In the foveopetal stimulus steady-state velocity was reduced in schizophrenic patients, only. Changes of saccadic latencies or position errors were not found in any of the patient groups. Also, pursuit latency was unchanged and initial eye acceleration was not decreased.Conclusions. Unaltered saccadic parameters indicate intact motion perception in cortical visual area V5. Therefore, the observed deficit of pursuit maintenance implies a dysfunction of frontal networks in all patient groups including the pursuit region of the frontal eye field (FEF). In patients with schizophrenia and affective disorder reduced post-saccadic pursuit initiation may indicate an impaired interaction between the pursuit and the saccadic system.
A comprehensive procedure to measure the body dimensions of large African predators with comments on the repeatability of measurements taken from an immobilized African lion (Panthera leo)
Authors: de Waal H. O. , Combrinck W. J. , Borstlap D. G. 
Published: March 2004

AbstractSpecific procedures are described to measure the body dimensions of large African predators; these include measurements of body and tail length, head, canines, mane, limbs, paws and testes. Data on body mass and dimensions were collected from an immobilized sub‐adult male African lion Panthera leo. He was 40 months old and weighed 190 kg. After being immobilized, data on body mass and dimensions were collected by a team comprising a scribe, two operators and assistants. The procedures of measuring the 43 variables on body dimensions were then repeated three times in quick succession, each session lasting about 10 min. The four sessions were handled as if a different individual was measured each time. Except for reports on body mass of lions, there is a paucity of comparable data in the literature for most of the variables presented in this paper. The small dispersion measures of the 43 variables suggest that the specific procedures to measure the body dimensions of a large African predator such as the lion have a high degree of repeatability and can be applied with confidence. The procedure has been used to obtain data on body dimensions of a large number of lions as well as dead specimens of black‐backed jackal Canis mesomelas, caracal Caracal caracal and Cape fox Vulpes chama. The data form part of a database on body dimensions of large African predators created by ALPRU. The objective is to develop non‐invasive techniques to determine whether wild predator populations might have been subjected to abnormal growth and development as a result of negative impacts on their habitat and thus food base.
Low Dose Histone Deacetylase Inhibitor, Depsipeptide (FR901228), Promotes Adenoviral Transduction in Human Rhabdomyosarcoma Cell Lines
Authors: Navid Fariba , Mischen Blaine T. , Helman Lee J. 
Published: March 2004

Purpose. Transduction of rhabdomyosarcoma (RMS) cells with adenoviral vectors for in vivo and in vitro applications has been limited by the low to absent levels of coxackie and adenovirus receptor (CAR). This study investigates the potential use of low doses of a histone deacetylase inhibitor, depsipeptide (FR901228), currently in Phase II human trials, to enhance adenoviral uptake in six rhabdomyosarcoma cell lines.Methods. Differences in adenoviral uptake in the presence and absence of depsipeptide (FR901228) were assessed using an adenoviral construct tagged with green fluorescent protein. Changes in CAR and αv integrin expression RMS in response to pretreatment with depsipeptide (FR901128) was determined using RT‐PCR.Results. Pretreatment of five of six RMS cell lines with 0.5 ng/ml of depsipeptide (FR901228) for 72 h resulted in increased viral uptake as assessed by green fluorescent protein expression. RT‐PCR analysis for CAR showed that in four of these five cell lines, CAR expression was increased 2.8–8.1‐fold in cells treated with depsipeptide (FR901228) as compared to control. αv integrin expression was substantially increased in the one cell line, RH5, which showed increased GFP expression in response to depsipeptide (FR901228) pretreatment but a minimal increase in CAR expression.Conclusions. Depsipeptide (FR901228) can be used as a vehicle to enhance adenoviral transduction in a majority of RMS cells. The mechanism of increased viral uptake appears to mediate via upregulation of CAR.
Osteosarcoma Associated With Diamond‐Blackfan Anaemia: A Case of a Child Receiving Growth Hormone Therapy
Authors: Lee Robert S. , Higgs Deborah , Haddo Omar , Pringle Jean , Briggs Timothy W. R. 
Published: March 2004

Purpose: Diamond–Blackfan anaemia (DBA) is a rare pure congenital red cell aplasia, usually presenting in infancy or early childhood. The literature suggests a predisposition to haemopoietic malignancy but in addition solid tumours have been reported, with five cases of osteosarcoma described.Patient: A sixth case of a 12‐year‐old girl with DBA who developed an osteosarcoma of the distal femur is presented.Results: She was treated with methotrexate followed by tumour excision and distal femoral replacement. The patient is currently alive with multiple pulmonary metastases.Discussion: We discuss the association between the administration of growth hormone and future development of malignancy in patients with DBA.
Molecular dynamics and free energy analysis of neuraminidase–ligand interactions
Authors: Bonnet Pascal , Bryce Richard A. 
Published: March 2004

AbstractWe report molecular dynamics calculations of neuraminidase in complex with an inhibitor, 4‐amino‐2‐deoxy‐2,3‐didehydro‐N‐acetylneuraminic acid (N‐DANA), with subsequent free energy analysis of binding by using a combined molecular mechanics/continuum solvent model approach. A dynamical model of the complex containing an ionized Glu119 amino acid residue is found to be consistent with experimental data. Computational analysis indicates a major van der Waals component to the inhibitor‐neuraminidase binding free energy. Based on the N‐DANA/neuraminidase molecular dynamics trajectory, a perturbation methodology was used to predict the binding affinity of related neuraminidase inhibitors by using a force field/Poisson‐Boltzmann potential. This approach, incorporating conformational search/local minimization schemes with distance‐dependent dielectric or generalized Born solvent models, correctly identifies the most potent neuraminidase inhibitor. Mutation of the key ligand four‐substituent to a hydrogen atom indicates no favorable binding free energy contribution of a hydroxyl group; conversely, cationic substituents form favorable electrostatic interactions with neuraminidase. Prospects for further development of the method as an analysis and rational design tool are discussed.
HIV‐1 protease molecular dynamics of a wild‐type and of the V82F/I84V mutant: Possible contributions to drug resistance and a potential new target site for drugs
Authors: Perryman Alexander L. , Lin Jung‐Hsin , McCammon J. Andrew 
Published: March 2004

AbstractThe protease from type 1 human immunodeficiency virus (HIV‐1) is a critical drug target against which many therapeutically useful inhibitors have been developed; however, the set of viral strains in the population has been shifting to become more drug‐resistant. Because indirect effects are contributing to drug resistance, an examination of the dynamic structures of a wild‐type and a mutant could be insightful. Consequently, this study examined structural properties sampled during 22 nsec, all atom molecular dynamics (MD) simulations (in explicit water) of both a wild‐type and the drug‐resistant V82F/I84V mutant of HIV‐1 protease. The V82F/I84V mutation significantly decreases the binding affinity of all HIV‐1 protease inhibitors currently used clinically. Simulations have shown that the curling of the tips of the active site flaps immediately results in flap opening. In the 22‐nsec MD simulations presented here, more frequent and more rapid curling of the mutant's active site flap tips was observed. The mutant protease's flaps also opened farther than the wild‐type's flaps did and displayed more flexibility. This suggests that the effect of the mutations on the equilibrium between the semiopen and closed conformations could be one aspect of the mechanism of drug resistance for this mutant. In addition, correlated fluctuations in the active site and periphery were noted that point to a possible binding site for allosteric inhibitors.
Substrate binding mode and reaction mechanism of undecaprenyl pyrophosphate synthase deduced from crystallographic studies
Authors: Chang Sing‐Yang , Ko Tzu‐Ping , Chen Annie P.‐C. , Wang Andrew H.‐J. , Liang Po‐Huang 
Published: March 2004

AbstractUndecaprenyl pyrophosphate synthase (UPPs) catalyzes eight consecutive condensation reactions of farnesyl pyrophosphate (FPP) with isopentenyl pyrophosphate (IPP) to form a 55‐carbon long‐chain product. We previously reported the crystal structure of the apo‐enzyme from Escherichia coli and the structure of UPPs in complex with sulfate ions (resembling pyrophosphate of substrate), Mg2+, and two Triton molecules (product‐like). In the present study, FPP substrate was soaked into the UPPs crystals, and the complex structure was solved. Based on the crystal structure, the pyrophosphate head group of FPP is bound to the backbone NHs of Gly29 and Arg30 as well as the side chains of Asn28, Arg30, and Arg39 through hydrogen bonds. His43 is close to the C2 carbon of FPP and may stabilize the farnesyl cation intermediate during catalysis. The hydrocarbon moiety of FPP is bound with hydrophobic amino acids including Leu85, Leu88, and Phe89, located on the α3 helix. The binding mode of FPP in cis‐type UPPs is apparently different from that of trans‐type and many other prenyltransferases which utilize Asprich motifs for substrate binding via Mg2+. The new structure provides a plausible mechanism for the catalysis of UPPs.
Factors involved in the stability of isolated β‐sheets: Turn sequence, β‐sheet twisting, and hydrophobic surface burial
Authors: Santiveri Clara M. , Santoro Jorge , Rico Manuel , Jiménez M. Angeles 
Published: March 2004

AbstractWe have recently reported on the design of a 20‐residue peptide able to form a significant population of a three‐stranded up‐and‐down antiparallel β‐sheet in aqueous solution. To improve our β‐sheet model in terms of the folded population, we have modified the sequences of the two 2‐residue turns by introducing the segment DPro‐Gly, a sequence shown to lead to more rigid type II′ β‐turns. The analysis of several NMR parameters, NOE data, as well as ΔδCαH, ΔδCβ, and ΔδCβ values, demonstrates that the new peptide forms a β‐sheet structure in aqueous solution more stable than the original one, whereas the substitution of the DPro residues by LPro leads to a random coil peptide. This agrees with previous results on β‐hairpin‐forming peptides showing the essential role of the turn sequence for β‐hairpin folding. The well‐defined β‐sheet motif calculated for the new designed peptide (pair‐wise RMSD for backbone atoms is 0.5 ± 0.1 Å) displays a high degree of twist. This twist likely contributes to stability, as a more hydrophobic surface is buried in the twisted β‐sheet than in a flatter one. The twist observed in the up‐and‐down antiparallel β‐sheet motifs of most proteins is less pronounced than in our designed peptide, except for the WW domains. The additional hydrophobic surface burial provided by β‐sheet twisting relative to a “flat” β‐sheet is probably more important for structure stability in peptides and small proteins like the WW domains than in larger proteins for which there exists a significant contribution to stability arising from their extensive hydrophobic cores.
Experimentally based topology models for E. coli inner membrane proteins
Authors: Rapp Mikaela , Drew David , Daley Daniel O. , Nilsson Johan , Carvalho Tiago , Melén Karin , De Gier Jan‐Willem , Von Heijne Gunnar 
Published: March 2004

AbstractMembrane protein topology predictions can be markedly improved by the inclusion of even very limited experimental information. We have recently introduced an approach for the production of reliable topology models based on a combination of experimental determination of the location (cytoplasmic or periplasmic) of a protein's C terminus and topology prediction. Here, we show that determination of the location of a protein's C terminus, rather than some internal loop, is the best strategy for large‐scale topology mapping studies. We further report experimentally based topology models for 31 Escherichia coli inner membrane proteins, using methodology suitable for genome‐scale studies.
Diversity and community composition of butterflies and odonates in an ENSO‐induced fire affected habitat mosaic: a case study from East Kalimantan, Indonesia
Authors: Cleary Daniel F. R. , Mooers Arne Ø. , Eichhorn Karl A. O. , Van Tol Jan , De Jong Rienk , Menken Steph B. J. 
Published: March 2004

Little is known about the diversity of tropical animal communities in recently fire‐affected environments. Here we assessed species richness, evenness, and community similarity of butterflies and odonates in landscapes located in unburned isolates and burned areas in a habitat mosaic that was severely affected by the 1997/98 ENSO (El Niño Southern Oscillation) event in east Kalimantan, Indonesian Borneo. In addition related community similarity to variation in geographic distance between sampling sites and the habitat/vegetation structure Species richness and evenness differed significantly among landscapes but there was no congruence between both taxa. The species richness of butterflies was, for example, highest in sites located in a very large unburned isolate whereas odonate species richness was highest in sites located in a small unburned isolate and once‐burned forest. We also found substantial variation in the habitat/vegetation structure among landscapes but this was mainly due to variation between unburned and burned landscapes and variation among burned landscapes.Both distance and environment (habitat/vegetation) contributed substantially to explaining variation in the community similarity (beta diversity) of both taxa. The contribution of the environment was, however, mainly due to variation between unburned and burned landscapes, which contained very different assemblages of both taxa. Sites located in the burned forest contained assemblages that were intermediate between assemblages from sites in unburned forest and sites from a highly degraded slash‐and‐burn area indicating that the burned forest was probably recolonised by species from these disparate environments. We, furthermore, note that in contrast to species richness (alpha diversity) the patterns of community similarity (beta diversity) were highly congruent between both taxa. These results indicate that community‐wide multivariate measures of beta diversity are more consistent among taxa and more reliable indicators of disturbance, such as ENSO‐induced burning, than univariate measures.
Reducing red cell transfusion by audit, education and a new guideline in a large teaching hospital
Authors: Garrioch M. , Sandbach J. , Pirie E. , Morrison A. , Todd A. , Green R. 
Published: March 2004

Summary.  Safety concerns combined with the greatly increased costs and difficulties of maintaining the blood supply are major considerations for transfusion services. Previous local surveys demonstrated that hospital blood use at our hospital could be improved. Excessive cross‐matching, unnecessary transfusion and high return rates of unused blood were commonplace.Transfusion practice was audited over a 3‐month period. An education package with guidelines for transfusion was delivered to all clinician groups within the hospital, over the following 9 months. The audit was repeated exactly 1 year later at the same time period.During the second audit, inpatient hospital numbers increased by 1·02% (from n = 7262 to n = 7336) but no differences in length of stay, cardiovascular morbidity or mortality were demonstrated. Twenty percent (n = 254, 2002; n = 316, 2001) fewer patients received blood, and the number of red cell packs used reduced by 19% (from n = 1093 to n = 880). Total number of patients transfused reduced from 4·4% to 3·5% which, as an absolute difference, is a reduction of 0·9% (CI 0·3–1·5, P = 0·006). The audit, guideline and education package had a major impact on red cell use within the hospital with no adverse effects.Blood use can be improved by the implementation of a suitable education package and guideline. If it is possible to replicate the results of this education programme nationwide, the effect on blood use, with subsequent savings and enhanced patient safety could be significant.
Patients prescribed injectable heroin or methadone —their opinions and experiences of treatment
Authors: Sell Louise , Zador Deborah 
Published: March 2004

ABSTRACTAims  To describe the opinions and experiences of treatment of a cohort of patients prescribed injectable opiate treatment (IOT).Design, setting, participants  Cross‐sectional survey of all patients on injectable diamorphine or methadone at a tertiary referral clinic in the northwest of England in June 2000.Findings  A total of 104 subjects were prescribed IOT, mostly male (87.5%) and with a mean age of 36.3 years (SEM 0.66, range 20–53). The majority (75.0%) were prescribed injectable methadone with the remainder (25.0%) on injectable diamorphine. Most subjects (93.3%) used intravenously, many (58.7%) into the femoral vein. Treatment was sought most frequently in order to procure a drug supply of known dose and purity, to improve family relationships and to avoid trouble with the police. Half were satisfied with their treatment but many wanted to change to injectable diamorphine or to increase their doses. Subjects cited many advantages of injectable diamorphine over injectable methadone, although benefits of injectable methadone were acknowledged.Conclusions  Subjects articulated a consistent desire for IOT in order to ‘stabilize’ their lives in a number of ways. This sample was recruited from one of the country's largest specialist IOT clinics. The generalizability of this study's findings to all patients in the United Kingdom currently prescribed IOT, however, was not examined. Nevertheless, these findings suggest that clinicians and policy makers should be aware of many heroin users’ perception of IOT as long‐term treatment and their clear preference for injectable diamorphine. Further investigation of differential outcomes between oral and injectable OT and between different injectable opiates is warranted.
Heroin and cocaine abusers have higher discount rates for delayed rewards than alcoholics or non‐drug‐using controls
Authors: Kirby Kris N. , Petry Nancy M. 
Published: March 2004

ABSTRACTAims  To test a prediction of the discounting model of impulsiveness that discount rates would be positively associated with addiction. The delay‐discount rate refers to the rate of reduction in the present value of a future reward as the delay to that reward increases.Design and measurements  We estimated participants’ discount rates on the basis of their pattern of choices between smaller immediate rewards ($11–80) and larger, delayed rewards ($25–85; at delays from 1 week to 6 months) in a questionnaire format. Participants had a one‐in‐six chance of winning a reward that they chose on one randomly selected trial.Participants and setting  Heroin (n = 27), cocaine (n = 41) and alcohol (n = 33) abusers and non‐drug‐using controls (n = 44) were recruited from advertisements. They were tested in a drug abuse research clinic at a medical school.Findings  On average, the cocaine and heroin groups had higher rates than controls (both P < 0.001), but alcoholics did not (P = 0.44). Abstinence was associated with lower rates for heroin abusers (P = 0.03), but not for cocaine or alcohol abusers (both P > 0.50).Conclusions  These data suggest that discount rates vary with the preferred drug of abuse, and that high discount rates should be considered in the development of substance abuse prevention and treatment efforts.
Heroin diffusion in the mid‐Hudson region of New York State
Authors: Furst R. Terry , Herrmann Christopher , Ray Leung  , Galea John , Hunt Kirsten 
Published: March 2004

ABSTRACTAims  Prompted by the history of heroin diffusion in the United States, press reports and building on previous research into retail heroin distribution, ethnographic research was undertaken identifying and describing retail distribution and diffusion of heroin in and into medium‐ and small‐sized towns in the mid‐Hudson region of New York State.Methods  In conjunction with fieldwork, in‐depth tape‐recorded interviews were conducted with recent admissions (30 days) at 28 different drug treatment facilities located in the region. Interviews were also conducted with drug counselors, narcotic officers, drug treatment administrators and the county commissioners of mental hygiene.Findings  Heroin‐dependent individuals who have access to cheaper heroin in urban areas, such as New York City, Newark, and Patterson, New Jersey, drive retail heroin distribution in the mid‐Hudson region. They travel to these cities, purchase heroin in quantity (costing $8–10 per bag), return to the region and sell premium‐priced heroin ($20‐$25 per bag) mostly to irregular users who do not have access to retail drug sellers in urban areas.Conclusion  Price disparity contributes to a recurrent process whereby irregular users who are able to gain access to cheaper heroin in urban areas, return to the mid‐Hudson and sell premium‐priced heroin to other users who do not have access to cheaper heroin. This process contributes to the diffusion of heroin abuse.
Cannabis use and the risk of later schizophrenia: a review
Authors: Smit Filip , Bolier Linda , Cuijpers Pim 
Published: March 2004

ABSTRACTAim  To study the role of cannabis use in the onset of symptoms and disorders in the schizophrenia spectrum.Design  Review of five population‐based, longitudinal studies on the relationship between cannabis use and problems ranging from the experience of psychotic symptoms to hospitalization with a confirmed diagnosis of schizophrenia. Several hypotheses are examined that may explain this relationship: (1) self‐medication; (2) effects of other drugs; (3) confounding; (4) stronger effect in predisposed people, and (5) etiological hypothesis.Findings  Hypotheses 1 and 2 can be dismissed; hypothesis 3 is still open to debate, and converging evidence is found for hypotheses 4 and 5—antecedent cannabis use appears to act as a risk factor in the onset of schizophrenia, especially in vulnerable people, but also in people without prior history.Conclusion  There is an intrinsic message here for public health, but how that message is to be translated into action is not immediately clear.