bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Highly Active Antiretroviral Therapy and Immunologic Status on Hepatitis C Virus Quasispecies Diversity in Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients
Authors: Babik Jennifer M. , Holodniy Mark
Published: January 2003

This study analyzes the effect of highly active antiretroviral therapy (HAART), and thus immunologic status, on hepatitis C virus (HCV) load and quasispecies diversity in patients coinfected with the human immunodeficiency virus (HIV) and HCV. Three cohorts of coinfected patients were analyzed retrospectively over a period of 7 to 10 months: group A was antiretroviral drug naïve at baseline and then on HAART for the remainder of the study, group B did not receive antiretroviral therapy at any point, and group C was on HAART for the entire study. HCV quasispecies diversity was analyzed by sequencing hypervariable region 1. In a longitudinal analysis, there was no significant change from baseline in any immunologic, virologic, or quasispecies parameter in any of the three groups. However, in comparison to groups A and B, group C had significantly higher CD4
+
- and CD8
+
-cell counts, a trend toward a higher HCV load, and significantly increased number of HCV clones, entropy, genetic distance, and ratio of nonsynonymous substitutions per nonsynonymous site to synonymous substitutions per synonymous site (

K
a

/

K
s

). In addition, CD4
+
-cell count was positively correlated with HCV load, genetic distance, and

K
a

. Interestingly, patients infected with HCV genotype 2 or 3 had a significantly higher CD4
+
-cell count, HCV load, genetic distance, and

K
a

/

K
s

than those infected with genotype 1. These results suggest that there is no immediate effect of HAART on HCV but that, with prolonged HAART, immune restoration results in an increase in HCV load and quasispecies diversity.
Importance of Basic Residues in Binding of Rous Sarcoma Virus Nucleocapsid to the RNA Packaging Signal
Authors: Lee Eun-gyung , Alidina Annie , May Cynthia , Linial Maxine L.
Published: January 2003

In the context of the Rous sarcoma virus Gag polyprotein, only the nucleocapsid (NC) domain is required to mediate the specificity of genomic RNA packaging. We have previously showed that the
Saccharomyces cerevisiae
three-hybrid system provides a rapid genetic assay to analyze the RNA and protein components of the avian retroviral RNA-Gag interactions necessary for specific encapsidation. In this study, using both site-directed mutagenesis and in vivo random screening in the yeast three-hybrid binding assay, we have examined the amino acids in NC required for genomic RNA binding. We found that we could delete either of the two Cys-His boxes without greatly abrogating either RNA binding or packaging, although the two Cys-His boxes are likely to be required for efficient viral assembly and release. In contrast, substitutions for the Zn-coordinating residues within the boxes did prevent RNA binding, suggesting changes in the overall conformation of the protein. In the basic region between the two Cys-His boxes, three positively charged residues, as well as basic residues flanking the two boxes, were necessary for both binding and packaging. Our results suggest that the stretches of positively charged residues within NC that need to be in a proper conformation appear to be responsible for selective recognition and binding to the packaging signal (Ψ)-containing RNAs.
Exonic Splicing Enhancer-Dependent Selection of the Bovine Papillomavirus Type 1 Nucleotide 3225 3′ Splice Site Can Be Rescued in a Cell Lacking Splicing Factor ASF/SF2 through Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway
Authors: Liu Xuefeng , Mayeda Akila , Tao Mingfang , Zheng Zhi-Ming
Published: January 2003

Bovine papillomavirus type 1 (BPV-1) late pre-mRNAs are spliced in keratinocytes in a differentiation-specific manner: the late leader 5′ splice site alternatively splices to a proximal 3′ splice site (at nucleotide 3225) to express L2 or to a distal 3′ splice site (at nucleotide 3605) to express L1. Two exonic splicing enhancers, each containing two ASF/SF2 (alternative splicing factor/splicing factor 2) binding sites, are located between the two 3′ splice sites and have been identified as regulating alternative 3′ splice site usage. The present report demonstrates for the first time that ASF/SF2 is required under physiological conditions for the expression of BPV-1 late RNAs and for selection of the proximal 3′ splice site for BPV-1 RNA splicing in DT40-ASF cells, a genetically engineered chicken B-cell line that expresses only human ASF/SF2 controlled by a tetracycline-repressible promoter. Depletion of ASF/SF2 from the cells by tetracycline greatly decreased viral RNA expression and RNA splicing at the proximal 3′ splice site while increasing use of the distal 3′ splice site in the remaining viral RNAs. Activation of cells lacking ASF/SF2 through anti-immunoglobulin M-B-cell receptor cross-linking rescued viral RNA expression and splicing at the proximal 3′ splice site and enhanced Akt phosphorylation and expression of the phosphorylated serine/arginine-rich (SR) proteins SRp30s (especially SC35) and SRp40. Treatment with wortmannin, a specific phosphatidylinositol 3-kinase/Akt kinase inhibitor, completely blocked the activation-induced activities. ASF/SF2 thus plays an important role in viral RNA expression and splicing at the proximal 3′ splice site, but activation-rescued viral RNA expression and splicing in ASF/SF2-depleted cells is mediated through the phosphatidylinositol 3-kinase/Akt pathway and is associated with the enhanced expression of other SR proteins.
Determinant for Endoplasmic Reticulum Retention in the Luminal Domain of the Human Cytomegalovirus US3 Glycoprotein
Authors: Lee Sungwook , Park Boyoun , Ahn Kwangseog
Published: January 2003

US3 of human cytomegalovirus is an endoplasmic reticulum resident transmembrane glycoprotein that binds to major histocompatibility complex class I molecules and prevents their departure. The endoplasmic reticulum retention signal of the US3 protein is contained in the luminal domain of the protein. To define the endoplasmic reticulum retention sequence in more detail, we have generated a series of deletion and point mutants of the US3 protein. By analyzing the rate of intracellular transport and immunolocalization of the mutants, we have identified Ser
58
, Glu
63
, and Lys
64
as crucial for retention, suggesting that the retention signal of the US3 protein has a complex spatial arrangement and does not comprise a contiguous sequence of amino acids. We also show that a modified US3 protein with a mutation in any of these amino acids maintains its ability to bind class I molecules; however, such mutated proteins are no longer retained in the endoplasmic reticulum and are not able to block the cell surface expression of class I molecules. These findings indicate that the properties that allow the US3 glycoprotein to be localized in the endoplasmic reticulum and bind major histocompatibility complex class I molecules are located in different parts of the molecule and that the ability of US3 to block antigen presentation is due solely to its ability to retain class I molecules in the endoplasmic reticulum.
Noninvasive Detection of New Simian Immunodeficiency Virus Lineages in Captive Sooty Mangabeys: Ability To Amplify Virion RNA from Fecal Samples Correlates with Viral Load in Plasma
Authors: Ling Binhua , Santiago Mario L. , Meleth Sreelatha , Gormus Bobby , McClure Harold M. , Apetrei Cristian , Hahn Beatrice H. , Marx Preston A.
Published: January 2003

The sooty mangabey (SM) (Cercocebus atys) is the natural host of a simian immunodeficiency virus, termed SIVsm, which gave rise to human immunodeficiency virus type 2. Data on the geographic distribution, prevalence, and genetic diversity of SIVsm in the wild remains limited. To address this issue, noninvasive strategies based on screening SM fecal and urine specimens for SIVsm-specific antibodies and virion RNA (vRNA) were developed, and the results were correlated with viral loads in plasma. Twenty-three SIVsm-infected and 27 uninfected SMs were evaluated. Time-matched urine, fecal and plasma samples were collected over a 2-month period from 16 captive naturally infected SMs. The remaining 7 infected and 27 uninfected SMs were sampled once. Each specimen was subjected to enhanced chemiluminescence-Western blot analysis and nested reverse transcriptase (RT) PCR. The results showed that urine was highly sensitive (96%) and specific (100%) for detection of SIVsm antibodies, while fecal detection was much less sensitive (16%). Conversely, vRNA detection was more sensitive in feces (50%) than in urine (2%) samples. Fecal-vRNA detection correlated with viral loads in plasma (P< 0.002). SMs with detectable fecal vRNA had a mean viral load in plasma of 458,006 copies/ml, while those with undetectable fecal vRNA had a mean viral load in plasma of 29,428 copies/ml. Moreover, for every log increase in the viral load in plasma, the odds of detecting virus in fecal samples increased 87-fold. Genetic diversity of SIVsm in the SM colony was characterized by sequencing partialgag(846 bp) andgp43(439 bp) fragments. Surprisingly, four new SIVsm lineages were identified, two of which were initially detected by fecal RT-PCR. This study documents the suitability of noninvasive methods for the detection and molecular characterization of new SIV variants. These assays will be useful for studying the phylogeny and epidemiology of SIVsm infections in the wild, and they hold promise as tools for investigating natural SIV infections in endangered nonhuman primates.
The Foot-and-Mouth Disease Virus
cis
-Acting Replication Element (
cre
) Can Be Complemented in
trans
within Infected Cells
Authors: Tiley Laurence , King Andrew M. Q. , Belsham Graham J.
Published: January 2003

A temperature-sensitive (
ts
) mutation was identified within the 5′-untranslated region of foot-and-mouth disease virus (FMDV) RNA. The mutation destabilizes a stem-loop structure recently identified as a
cis
-acting replication element (
cre
). Genetic analyses indicated that the
ts
defect in virus replication could be complemented. Thus, the FMDV
cre
can function in
trans
. It is suggested that the
cre
be renamed a 3B-uridylylation site (
bus
).
Inheritance of microsatellite loci in the white sturgeon (Acipenser transmontanus)
Authors: Rodzen Jeff A , May Bernie
Published: January 2003

Nine tetramer motif (GATA)nmicrosatellite systems were developed for use in the white sturgeon, Acipenser transmontanus. We report inheritance patterns for these nine systems, which range from one possible disomic system to tetrasomy and octosomy, with some systems containing null alleles. Because of the complex modes of inheritance underlying these systems and the highly duplicated nature of the genome, we propose each allele be scored as its own dominant marker, similar to AFLPs or RAPDs. The utility of this method is validated by the observation that individual alleles within a microsatellite system generally fit the expectation for independent transmission and fit the expected transmission frequency for single copy nuclear markers.Key words: white sturgeon, Acipenser transmontanus, microsatellite, polyploid, inheritance, genetic markers.
Effectiveness of selective genotyping for detection of quantitative trait loci: an analysis of grain and malt quality traits in three barley populations
Authors: Ayoub M , Mather D E
Published: January 2003

Marker genotype data and grain and malt quality phenotype data from three barley (Hordeum vulgare L.) mapping populations were used to investigate the feasibility of selective genotyping for detection of quantitative trait loci (QTLs). With selective genotyping, only individuals with high and low phenotypic values for the trait of interest are genotyped. Here, genotyping of 10 to 70% of each population (i.e., 5 to 35% in each tail of the phenotypic distribution) was considered. Genomic positions detected by selective genotyping were compared to QTL position estimates from interval mapping analysis using marker genotype data from the entire population. Selective genotyping reliably detected almost all of the mapped QTLs, often with only 10% of the population genotyped. Selective genotyping also detected spurious QTLs in regions of the genome where no significant QTL had been mapped. Even with additional genotyping to verify putative QTLs, the total genotyping effort for detection of QTLs for a single trait by selective genotyping was usually less than 30% of that required for conventional interval mapping. Simultaneous investigation of two or more traits by selective genotyping would require additional genotyping effort, but could still be worthwhile.Key words: selective genotyping, quantitative trait loci, barley.
Rapid classification of partial waxy wheats using PCR-based markers
Authors: Nakamura T , Vrinten P , Saito M , Konda M
Published: January 2003

Mutations in the three homeologous waxy loci Wx-A1, Wx-B1, and Wx-D1 of a waxy wheat line have previously been characterized at the molecular level. Using combinations of these mutations, six types of partial waxy wheat plus wild type and waxy wheat (types 18) can be produced. Here, we describe primer sets for all three loci that can be used under a single set of conditions, allowing 32 lines to be characterized as types 18 in a single PCR run using a 96-well plate. Using multiplex PCR, mutations at the Wx-B1 and Wx-D1 loci can be identified in a single PCR, reducing the number of reactions necessary to identify and select the desired partial waxy wheat line. A single multiplex PCR can be used to detect all three mutations when products are analyzed using capillary electrophoresis on a microchip device. The PCR conditions and primers are effective with a number of cultivars from other countries, indicating that the mutations found at the Wx-A1 and Wx-B1 loci of these cultivars likely have the same origins as the mutations in the corresponding loci of the waxy wheat line used in this study. The PCR selection method described here is an easy and effective alternative to the commonly used SDSPAGE methods for identification of null alleles.Key words: partial waxy wheat, amylose, PCR, capillary electrophoresis, marker-assisted selection.
Mapping quantitative trait loci in inbred backcross lines ofLycopersicon pimpinellifolium(LA1589)
Authors: Doganlar Sami , Frary Anne , Ku Hsin-Mei , Tanksley Steven D
Published: January 2003

Although tomato has been the subject of extensive quantitative trait loci (QTLs) mapping experiments, most of this work has been conducted on transient populations (e.g., F2or backcross) and few homozygous, permanent mapping populations are available. To help remedy this situation, we have developed a set of inbred backcross lines (IBLs) from the interspecific cross between Lycopersicon esculentum cv. E6203 and L. pimpinellifolium (LA1589). A total of 170 BC2F1plants were selfed for five generations to create a set of homozygous BC2F6lines by single-seed descent. These lines were then genotyped for 127 marker loci covering the entire tomato genome. These IBLs were evaluated for 22 quantitative traits. In all, 71 significant QTLs were identified, 15% (11/71) of which mapped to the same chromosomal positions as QTLs identified in earlier studies using the same cross. For 48% (34/71) of the detected QTLs, the wild allele was associated with improved agronomic performance. A number of new QTLs were identified including several of significant agronomic importance for tomato production: fruit shape, firmness, fruit color, scar size, seed and flower number, leaf curliness, plant growth, fertility, and flowering time. To improve the utility of the IBL population, a subset of 100 lines giving the most uniform genome coverage and map resolution was selected using a randomized greedy algorithm as implemented in the software package MapPop (http://www.bio.unc.edu/faculty/vision/lab/mappop/). The map, phenotypic data, and seeds for the IBL population are publicly available (http://soldb.cit.cornell.edu) and will provide tomato geneticists and breeders with a genetic resource for mapping, gene discovery, and breeding.Key words: tomato, Lycopersicon esculentum, IBLs, QTL, mapping.
TWO-SCALE GEOMETRICAL RESONANCE: FROM PARAMETRIC RESONANCE IN AN OSCILLATOR TO THERMODYNAMIC CYCLES
Authors: BLIOKH K. YU , USATENKO O. V.
Published: January 2003

The paper deals with influence of two-scale variations of parameters on the behavior of different dynamical systems. By two-scale we mean parameter oscillations occur in an alternating manner with large and small temporal gradient, on a typical period intervals. The shape of such parameter dependence resembles relaxation oscillations. Parametric instability is revealed under these conditions. We call it two-scale geometric resonance (TGR). TGR can be described with the help of certain geometric structures on the extended phase space. TGR possesses similar properties and can be described in similar ways in seemingly different systems. The article presents general models for the TGR description and considers a few specific examples: classical oscillator, Van-der-Pol oscillator and thermodynamic system with ideal gas.
QUANTUM MECHANICAL TREATMENT OF THE ELECTRICAL INTERACTION VIEWED AS AN ELASTIC COUPLING THROUGH FLUX LINES
Authors: DOLOCAN ANDREI , DOLOCAN VOICU
Published: January 2003

Using the Lagrangian formalism we attempt to calculate the interaction energy between the two bodies, nonconnected and connected, in a linear lattice. The obtained results show that the interaction is dependent on the dispersion relation ω (q). On this basis we calculate the binding energy of an ionic lattice and we have found a good agreement with experimental data.
AN APPROACH TO A DYNAMIC SYSTEM SIMULATION BASED ON HUMAN INFORMATION PROCESSING
Authors: KOBAYASHI ICHIRO , SUGENO MICHIO
Published: January 2003

As we know that human intellectual activities are performed by the use of language; a human being thinks and reasons with language. In this paper, we propose a new simulation method which imitates human information processing based on the use of language. — An ordinary simulation method uses mathematical equations to estimate the future trends of a dynamic system, however, we propose a new simulation method which uses a model consists of natural language, which is called a linguistic model. A linguistic model does not have a fixed structure, but the structure of the model itself will be generated so that model should become the most appropriate model to estimate the future behavior of a dynamic system. We regard that human intellectual activities such as thinking, reasoning, etc. are also texts realized by context as well as a linguistic text is done by context. We show a human linguistic reasoning model generation with an example of forecast of foreign exchange rate (FER) changes.
CORRELATION OF FUZZY NUMBERS BY α-CUT METHOD
Authors: HUNG WEN-LIANG , WU JONG-WUU
Published: January 2003

In this paper, we propose a method to calculate the correlation coefficient of fuzzy numbers by means of "α-cut". This value obtained from our formula tells us not only the strength of relationship between the fuzzy numbers, but also whether the fuzzy numbers are positively or negatively related. This approach looks better than previous methods which only evaluate the strength of the relation. Furthermore, we extend the "α-cut" method to interval-valued fuzzy numbers. The value of the correlation coefficient between interval-valued fuzzy numbers lies in the interval [-1, 1], as computed from our formula.
A REUSE-ORIENTED WORKFLOW DEFINITION LANGUAGE
Authors: BLIN MARIE JOSÉ , WAINER JACQUES , MEDEIROS CLAUDIA BAUZER
Published: January 2003

This paper presents a new formalism for workflow process definition, which combines research in programming languages and in database systems. This formalism is based on creating a library of workflow building blocks, which can be progressively combined and nested to construct complex workflows. Workflows are specified declaratively, using a simple high level language, which allows the dynamic definition of exception handling and events, as well as dynamically overriding workflow definition. This ensures a high degree of flexibility in data and control flow specification, as well as in reuse of workflow specifications to construct other workflows. The resulting workflow execution environment is well suited to supporting cooperative work.
MODELS OF AND EXPERIMENTS WITH E-MARKETS FOR ELECTRIC UTILITIES
Authors: RAM VINUTHA , FINDLER NICHOLAS V. , MALYANKAR RAPHAEL M.
Published: January 2003

Many Multi-Agent Systems (MASs) have been built that represent different social structures, such as alliances, teams, coalitions, conventions and markets. Our primary objective in this work was to establish a fairly general-purpose market structure that can be reused in other market-based MASs. We have implemented different models of a deregulated electricity market. The models vary in the types of interaction between buyers and sellers, the mechanisms used to transact deals in the market, and in the role of the central agent. Extensive experiments were then conducted on the models to determine the type of market structure best suited for trading. The criteria of evaluation were based on resource consumption, number of deals completed, demand satisfied, supply used, excess-over-need bought, and prices paid. The conclusions should be applicable to other deregulated consumer markets of "perishable" commodities with strong time-dependence.
CLUSTERING OF CLIENT-SITES IN THREE-TIER DATABASE ARCHITECTURES
Authors: PARK JE-HO , KANITKAR VINAY , UMA R. N. , DELIS ALEX
Published: January 2003

Conventional two-tier databases have shown performance limitations in the presence of many concurrent clients. We propose logical grouping of clients (or clustering) as the means to improve the performance of collaborative networked databases. In this paper, we discuss a three-tier client-server database architecture (3t-CSD) featuring the above partitioning. The proposed clustering is based on the similarity of clients' access patterns. Each cluster is supervised by a designated manager that coordinates data sharing among its members. A number of clients is optimally partitioned if sites in each individual cluster have the maximum common data access probability possible. We initially show that the optimal client clustering problem is NP-complete and then we develop two approximate solutions based on abstraction and filtering of statistics for client access patterns. Our main goal is to compare the performance of the conventional and three-tier client-server database architecture with respect to the transaction turnaround times and object response times. After developing system prototypes that implement both two-tier and 3t-CSDs, we experimentally show that as long as good client-clustering is possible, the 3t-CSD architecture yields sizable gains over its conventional counterpart. We also compare and evaluate the effectiveness of the two proposed techniques used to create client clusters. Finally, we examine the role of several preprocessing schemes used to reduce the volume of the input data supplied to the clustering techniques.
TRUST MANAGEMENT THROUGH FUZZY REPUTATION
Authors: CARBO J. , MOLINA J. M. , DAVILA J.
Published: January 2003

Open electronic communities may bring together people geographically and culturally unrelated to each other. In this context, taking costly decisions depends on the expectations created according to past behaviour of others. This kind of information is usually called reputation and it is one of the most significant factors to trust merchants and recommenders in electronic commerce interactions. When agents are acting on behalf of humans in such commercial scenarios, they should represent and reason about trust and reputation as humans do. In this paper a trust management mechanism tackles the vague, subjective and uncertain information about others using fuzzy sets. The operations defined over such fuzzy sets updates the reputation of merchants according to the general situation faced. This trust management mechanism is applied to a multiagent system of merchants, recommenders and buyers, where collaborative recommendations coexist with competitive intentions. The developed multi-agent system is used to compare the level of success of predictions obtained from the fuzzy computations with some of the most well known (crisp) reputation mechanisms: ebay, bizrate, sporas and regret when the behaviour of merchants change in different degrees. Finally, the potential benefits of using fuzzy sets to manage reputation in multi-agent systems are analyzed according to the excellent experimental results shown.
ADAPTIVE AGENTS FOR EFFECTIVE INFORMATION MONITORING
Authors: LIU REY-LONG
Published: January 2003

Information motoring is an essential basis for management and decision making in various domains. Once an information update is detected, suitable procedures may be triggered to identify potential problems and opportunities. In this paper, we define effective information monitoring (EIM) and explore how adaptive agents may cooperate with each other in order to achieve their collective goal of EIM. Since each information item may be updated by various entities (e.g. information servers) at any time, EIM calls for a multiagent system that may detect more information updates in a timely manner using a controlled amount of system resources (e.g. loading of related information servers and the Intranet). To achieve EIM, the agents should adapt themselves to the dynamically changing behaviors of the information items being monitored. They learn to issue requests of using system resources and concede to those agents that are more likely to detect updates at the time of negotiation. The framework is theoretically and empirically evaluated. Its potential applications to management by exceptions are identified and discussed.
Calorie Restriction, Aging, and Cancer Prevention: Mechanisms of Action and Applicability to Humans
Authors: Hursting Stephen D. , Lavigne Jackie A. , Berrigan David , Perkins Susan N. , Barrett J. Carl
Published: January 2003

Calorie restriction (CR) is the most effective and reproducible intervention for increasing lifespan in a variety of animal species, including mammals. CR is also the most potent, broadly acting cancer-prevention regimen in experimental carcinogenesis models. Translation of the knowledge gained from CR research to human chronic disease prevention and the promotion of healthy aging is critical, especially because obesity, which is an important risk factor for several chronic diseases, including many cancers, is alarmingly increasing in the Western world. This review synthesizes the key biological mechanisms underlying many of the beneficial effects of CR, with a particular focus on the insulin-like growth factor–1 pathway. We also describe some of the opportunities now available for investigations, including gene expression profiling studies, the development of pharmacological mimetics of CR, and the integration of CR regimens with targeted, mechanism-based interventions. These approaches will facilitate the translation of CR research into strategies for effective human chronic disease prevention.
The Automated External Defibrillator: Critical Link in the Chain of Survival
Authors: Ramaswamy Karthik , Page Richard L.
Published: January 2003

Sudden death due to ventricular fibrillation (VF) is the leading cause of death in the United States. Early defibrillation is the most important determinant of survival and is the key element in cardiopulmonary resuscitation. Obstacles to rapid defibrillation by trained emergency personnel persist, but the development of the automated external defibrillator (AED) promises to realize the goal of widespread early defibrillation and translate to an improved chance for survival for the cardiac arrest victim. Technological advancements have made the AED safe, easy to use, accurate, and effective in terminating VF. Use of the AED by trained nontraditional first responders (e.g., firefighters, police officers, flight crews) has improved survival rates in a variety of settings and forms the basis for public-access defibrillation.
New Concepts in the Treatment of Rheumatoid Arthritis
Authors: Goldbach-Mansky Raphaela , Lipsky Peter E.
Published: January 2003

Recent advances have made rheumatoid arthritis (RA) amenable to treatment. Clinical studies in patients with early and established RA have broadened understanding of its pathogenesis and have fundamentally changed the therapeutic approach to this disease. Quantum leaps in therapy—including the use of early, aggressive therapy, combination therapy, and the introduction of anti-cytokine agents—have improved patients' quality of life, eased clinical symptoms, retarded the progression of joint destruction, and delayed disability. We review clinical evidence supporting these therapeutic approaches. Diagnostic and therapeutic challenges are highlighted, and a decision tree to guide treatment in patients with early or established RA is provided.
Genetics and Pathophysiology of Human Obesity
Authors: Cummings David E. , Schwartz Michael W.
Published: January 2003

Obesity has become a leading public health concern. Over 1 billion people are now overweight or obese, and the prevalence of these conditions is rising rapidly. Remarkable new insights into the mechanisms that control body weight are providing an increasingly detailed framework for a better understanding of obesity pathogenesis. Key peripheral signals, such as leptin, insulin, and ghrelin, have been linked to hypothalamic neuropeptide systems, and the anatomic and functional networks that integrate these systems have begun to be elucidated. This article highlights some of these recent findings and their implications for the future of obesity treatment.

“Banish plump Jack, and banish all the world.” William Shakespeare, King Henry IV Part 1
Studying Cancer Families to Identify Kidney Cancer Genes
Authors: Zbar Berton , Klausner Richard , Linehan W. Marston
Published: January 2003

We studied families with multiple members affected with renal cancer to delineate clinically distinct forms of inherited renal cancer, and to identify and characterize the genes responsible for these disorders. Today, cancer geneticists recognize seven clinically distinct, inherited forms of epithelial renal cancer; genes responsible for five inherited predispositions have been found. Positional cloning efforts for one kidney cancer gene are nearing completion. These discoveries will provide diagnostic tests for these diseases, a foundation for studies of the relationship between genotype and phenotype, and a basis for studies of the pathophysiology of the diverse types of epithelial renal cancer.
Effects of contrast material on computed tomographic measurements of lung volumes in patients with acute lung injury
Authors: Bouhemad Bélaid , Richecoeur Jack , Lu Qin , Malbouisson Luiz M , Cluzel Philippe , Rouby Jean-Jacques ,   and the CT Scan Study Group ARDS
Published: January 2003

Background

Intravenous injection of contrast material is routinely performed in order to differentiate nonaerated lung parenchyma from pleural effusion in critically ill patients undergoing thoracic computed tomography (CT). The aim of the present study was to evaluate the effects of contrast material on CT measurement of lung volumes in 14 patients with acute lung injury.

Method

A spiral thoracic CT scan, consisting of contiguous axial sections of 10 mm thickness, was performed from the apex to the diaphragm at end-expiration both before and 30 s (group 1; n = 7) or 15 min (group 2; n = 7) after injection of 80 ml contrast material. Volumes of gas and tissue, and volumic distribution of CT attenuations were measured before and after injection using specially designed software (Lungview®; Institut National des Télécommunications, Evry, France). The maximal artifactual increase in lung tissue resulting from a hypothetical leakage within the lung of the 80 ml contrast material was calculated.

Results

Injection of contrast material significantly increased the apparent volume of lung tissue by 83 ± 57 ml in group 1 and 102 ± 80 ml in group 2, whereas the corresponding maximal artifactual increases in lung tissue were 42 ± 52 ml and 31 ± 18 ml.

Conclusion

Because systematic injection of contrast material increases the amount of extravascular lung water in patients with acute lung injury, it seems prudent to avoid this procedure in critically ill patients undergoing a thoracic CT scan and to reserve its use for specific indications.
Esophageal capnometry during hemorrhagic shock and after resuscitation in rats
Authors: Totapally Balagangadhar R , Fakioglu Harun , Torbati Dan , Wolfsdorf Jack
Published: January 2003

Background

Splanchnic perfusion following hypovolemic shock is an important marker of adequate resuscitation. We tested whether the gap between esophageal partial carbon dioxide tension (PeCO2) and arterial partial carbon dioxide tension (PaCO2) is increased during graded hemorrhagic hypotension and reversed after blood reinfusion, using a fiberoptic carbon dioxide sensor.

Materials and method

Ten Sprague–Dawley rats were anesthetized, tracheotomized, and cannulated in one femoral artery and vein. A calibrated fiberoptic PCO2 probe was inserted into the distal third of the esophagus for determination of luminal PeCO2 during maintained anesthesia (pentobarbital 15 mg/kg per hour), normothermia (38 ± 0.5°C), and fluid balance (saline 5 ml/kg per hour). Three out of 10 rats were used to determine the limits of hemodynamic stability during gradual hemorrhage. Seven of the 10 rats were then subjected to mild and severe hemorrhage (15 and 20–25 ml/kg, respectively). Thirty minutes after severe hemorrhage, these rats were resuscitated by reinfusion of the shed blood. Arterial gas exchange, hemodynamic variables, and PeCO2 were recorded at each steady-state level of hemorrhage (at 30 and 60 min) and after resuscitation.

Results

The PeCO2–PaCO2 gap was significantly increased after mild and severe hemorrhage and returned to baseline (prehemorrhagic) values following blood reinfusion. Base deficit increased significantly following severe hemorrhage and remained significantly elevated after blood reinfusion. Significant correlations were found between base deficit and PeCO2–PaCO2 (P < 0.002) and PeCO2 (P < 0.022). Blood bicarbonate concentration decreased significantly following mild and severe hemorrhage, but its recovery was not complete at 60 min after blood reinfusion.

Conclusion

Esophageal–arterial PCO2 gap increases during graded hemorrhagic hypotension and returns to baseline value after resuscitation without complete reversal of the base deficit. These data suggest that esophageal capnometry could be used as an alternative for gastric tonometry during management of hypovolemic shock.
Should there be separate psychiatric services for ethnic minority groups?
Authors: Bhui Kamaldeep , Sashidharan Sashi P.
Published: January 2003

For decades there have been calls for psychiatric services to be more culturally competent. Frustration with a perceived slow pace of change has led to the development of separate services. For instance, in the USA, San Francisco General Hospital has psychiatric wards with different ‘ethnic focuses' – East Asian Americans, African Americans and Hispanic Americans are admitted to different wards. In the UK, the National Health Service has developed culturally specific services as well as funding voluntary sector services that target specific cultural or ethnic minority groups. Are such developments the correct way forward? Do they produce lasting change or just let general services off the hook? Can they work in major cities like London, Paris or New York where over a hundred languages are spoken?
Clinical effects of sexual abuse on people with learning disability
Authors: Sequeira Heather , Hollins Sheila
Published: January 2003

Background

There are few publications concerning the psychological reactions of people with learning disabilities to sexual abuse. Most significantly, there are no controlled studies and few which demonstrate a systematic approach to documenting the sequelae of trauma.

Aims

To critically review the published research in this field.

Method

A literature search in peer-reviewed psychiatry, psychology nursing and social care journals for the years 1974 to 2001 was conducted and 25 studies were reviewed.

Results

Several studies suggest that, following sexual abuse, people with learning disabilities may experience a range of psychopathology similar to that experienced by adults and children in the general population. However, because of methodological limitations, these results are not conclusive.

Conclusions

Whether people with learning disabilities experience reactions to sexual abuse similar to the general population has yet to be explored by systematic research.
Impact of the ICD–10 Primary Health Care (PHC) diagnostic and management guidelines for mental disorders on detection and outcome in primary care
Authors: Croudace Tim , Evans Jonathan , Harrison Glynn , Sharp Deborah J. , Wilkinson Ellen , McCann Gemma , Spence Mathew , Crilly Catherine , Brindle Lucy
Published: January 2003

Background

The World Health Organization (WHO) ICD–10 Primary Health Care (PHC) Guidelines for Diagnosis and Management of Mental Disorders (1996) have not been evaluated in a pragmatic randomised controlled trial (RCT).

Aims

To evaluate the effect of local adaptation and dissemination of the guidelines.

Method

Pragmatic, pair-matched, cluster RCT involving 30 practices.

Results

Guideline practices were less sensitive but more specific in identifying morbidity, but these differences were not significant. Guideline patients did not differ from usual-care patients on 12-item General Health Questionnaire scores at 3-month follow-up or in the proportion who were still cases. There were no significant differences in secondary outcomes.

Conclusions

Attempts to influence clinician behaviour through a process of adaptation and extension of guidelines are unlikely to change detection rates or outcomes.
Death rate from ischaemic heart disease in Western Australian psychiatric patients 1980–1998
Authors: Lawrence David M. , D'Arcy Cashel , Holman J. , Jablensky Assen V. , Hobbs Michael S. T.
Published: January 2003

Background

People with mental illness suffer excess mortality due to physical illnesses.

Aims

To investigate the association between mental illness and ischaemic heart disease (IHD) hospital admissions, revascularisation procedures and deaths.

Method

A population-based record-linkage study of 210 129 users of mental health services in Western Australia during 1980–1998. IHD mortality rates, hospital admission rates and rates of revascularisation procedures were compared with those of the general population.

Results

IHD (not suicide) was the major cause of excess mortality in psychiatric patients. In contrast to the rate in the general population, the IHS mortality rate in psychiatric patients did not diminish over time. There was little difference in hospital admission rates for IHD between psychiatric patients and the general community, but much lower rates of revascularisation procedures with psychiatric patients, particularly in people with psychoses.

Conclusions

People with mental illness do not receive an equitable level of intervention for IHD. More attention to their general medical care is needed.
Developmental precursors of child- and adolescent-onset schizophrenia and affective psychoses: diagnostic specificity and continuity with symptom dimensions
Authors: Hollis Chris
Published: January 2003

Background

An increased rate of premorbid impairment has been reported in both child- and adolescent-onset schizophrenic and affective psychoses.

Aims

To examine the evidence for a specific association between premorbid impairment and child- and adolescent-onset schizophrenia, and whether specific continuities exist between premorbid impairments and psychotic symptom dimensions.

Method

Retrospective case note study of 110 first-episode child- and adolescent-onset psychoses (age 10–17 years). DSM–III–R diagnoses derived from the OPCRIT algorithm showed 61 with schizophrenia (mean age 14.1 years) and 49 with other non-schizophrenic psychoses (mean age 14.7 years).

Results

Premorbid social impairment was more common in early-onset schizophrenia than in other early-onset psychoses (OR 1.9,P=0.03). Overall, impaired premorbid development, enuresis and incontinence during psychosis were specifically associated with the negative psychotic symptom dimension.

Conclusions

Premorbid social impairments are more marked in child- and adolescent-onset schizophrenia than in other psychoses. There appears to be developmental continuity from premorbid impairment to negative symptoms.
Nithsdale Schizophrenia Surveys 24: sexual dysfunction
Authors: Macdonald S. , Halliday J. , MacEwan T. , Sharkey V. , Farrington S. , Wall S. , McCreadie R. G.
Published: January 2003

Background

That sexual dysfunction occurs in schizophrenia is not in doubt. Previous studies have had weaknesses such as the use of selected populations or the absence of a control group.

Aims

To measure rates of sexual dysfunction in people with schizophrenia compared with the general population.

Method

Sexual dysfunction was assessed by a self-completed gender-specific questionnaire. Ninety-eight (73%) of 135 persons with schizophrenia and 81 (71%) of 114 persons recruited as controls returned the questionnaire.

Results

At least one sexual dysfunction was reported by 82% of men and 96% of women with schizophrenia. Male patients reported less desire for sex, were less likely to achieve and maintain an erection, were more likely to ejaculate more quickly and were less satisfied with the intensity of their orgasms. Female patients reported less enjoyment than the control group. Sexual dysfunction in female patients was associated with negative schizophrenic symptoms and general psychopathology. There was no association between sexual dysfunction and type of antipsychotic medication.

Conclusions

People with schizophrenia report much higher rates of sexual dysfunction than do the general population. Men and women with schizophrenia have a different pattern of sexual dysfunction.
Evaluation of a community-based rehabilitation model for chronic schizophrenia in rural India
Authors: Chatterjee Sudipto , Patel Vikram , Chatterjee Achira , Weiss Helen A.
Published: January 2003

Background

There are no community services for the majority of the estimated 10 million persons with schizophrenia in India. Community-based rehabilitation (CBR) is a model of care which has been widely used for physical disabilities in resource-poor settings.

Aims

To compare CBR with out-patient care (OPC) for schizophrenia in a resource-poor setting in India.

Method

A longitudinal study of outcome in patients with chronic schizophrenia contrasted CBR with OPC. Outcome measures were assessed using the Positive and Negative Symptom Scale and the modified WHO Disability Assessment Schedule at 12 months.

Results

Altogether, 207 participants entered the study, 127 in the CBR group and 80 in the OPC group. Among the 117 fully compliant participants the CBR model was more effective in reducing disability, especially in men. Within the CBR group, compliant participants had significantly better outcomes compared with partially compliant or non-complaint participants (P<0.001). Although the subjects in the CBR group were more socially disadvantaged, they had significantly better retention in treatment.

Conclusions

The CBR model is a feasible model of care for chronic schizophrenia in resource-poor settings.
Medical outcome of pregnancy in women with psychotic disorders and their infants in the first year after birth
Authors: Howard Louise M. , Goss Claudia , Leese Morven , Thornicroft Graham
Published: January 2003

Background

There has been little research into the health of infants of women with psychotic disorders.

Aims

To investigate the antenatal care of mothers with a history of psychotic disorders, obstetric outcomes and the subsequent health of their babies.

Method

A matched, controlled cohort study was carried out using the General Practice Research Database. Women with a history of a psychotic disorder, who gave birth in 1996–1998, were compared with women matched for age and general practice (199 cases and 787 controls) and their infants.

Results

Cases had a higher proportion of stillbirths (OR=4.03, 95% CI 1.14–4.25,P=0.03) and neonatal deaths (P<0.001). There was no difference in gestational age at antenatal booking. Mothers with psychotic disorders were less likely than controls to attend for infant immunisations 90–270 days after birth (RR=0.94, 95% CI 0.88–0.99,P=0.03). There was no significant difference in the rates of accidents and hospital contacts for infants.

Conclusions

There is an increased risk of stillbirth and neonatal death in women with a history of psychotic disorder, and it is therefore important for health care professionals to focus on optimal obstetric care. The physical health of babies who live with mothers with psychotic disorders is not significantly different from that of matched baby controls.
Discrimination and delusional ideation
Authors: Janssen I. , Hanssen M. , Bak M. , Bijl R. V. , De Graaf R. , Vollebergh W. , McKenzie K. , Van Os J.
Published: January 2003

Background

In the UK and The Netherlands, people with high rates of psychosis are chronically exposed to discrimination.

Aims

To test whether perceived discrimination is associated longitudinally with onset of psychosis.

Method

A 3-year prospective study of cohorts with no history of psychosis and differential rates of reported discrimination on the basis of age, gender, disability, appearance, skin colour or ethnicity and sexual orientation was conducted in the Dutch general population (n=4076). The main outcome was onset of psychotic symptoms (delusions and hallucinations).

Results

The rate of delusional ideation was 0.5% (n=19) in those who did not report discrimination, 0.9% (n=4) in those who reported discrimination in one domain, and 2.7% (n=3) in those who reported discrimination in more than one domain (exactP=0.027). This association remained after adjustment for possible confounders. No association was found between baseline discrimination and onset of hallucinatory experiences.

Conclusions

Perceived discrimination may induce delusional ideation and thus contribute to the high observed rates of psychotic disorder in exposed minority populations.