bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization of genomic sequence information to develop malaria vaccines
Authors: Doolan D. L. , Aguiar J. C. , Weiss W. R. , Sette A. , Felgner P. L. , Regis D. P. , Quinones-Casas P. , Yates J. R. , Blair P. L. , Richie T. L. , Hoffman S. L. , Carucci D. J. 
Published: September 2003

SUMMARYRecent advances in the fields of genomics, proteomics and molecular immunology offer tremendous opportunities for the development of novel interventions against public health threats, including malaria. However, there is currently no algorithm that can effectively identify the targets of protective T cell or antibody responses from genomic data. Furthermore, the identification of antigens that will stimulate the most effective immunity against the target pathogen is problematic, particularly if the genome is large. Malaria is an attractive model for the development and validation of approaches to translate genomic information to vaccine development because of the critical need for effective anti-malarial interventions and because the Plasmodium parasite is a complex multistage pathogen targeted by multiple immune responses. Sterile protective immunity can be achieved by immunization with radiation-attenuated sporozoites, and anti-disease immunity can be induced in residents in malaria-endemic areas. However, the 23 Mb Plasmodium falciparum genome encodes more than 5300 proteins, each of which is a potential target of protective immune responses. The current generation of subunit vaccines is based on a single or few antigens and therefore might elicit too narrow a breadth of response. We are working towards the development of a new generation vaccine based on the presumption that duplicating the protection induced by the whole organism may require a vaccine nearly as complex as the organism itself. Here, we present our strategy to exploit the genomic sequence of P. falciparum for malaria vaccine development.
Gene vector and transposable element behavior in mosquitoes
Authors: O'Brochta David A. , Sethuraman Nagaraja , Wilson Raymond , Hice Robert H. , Pinkerton Alexandra C. , Levesque Cynthia S. , Bideshi Dennis K. , Jasinskiene Nijole , Coates Craig J. , James Anthony A. , Lehane Michael J. , Atkinson Peter W. 
Published: September 2003

SUMMARYThe development of efficient germ-line transformation technologies for mosquitoes has increased the ability of entomologists to find, isolate and analyze genes. The utility of the currently available systems will be determined by a number of factors including the behavior of the gene vectors during the initial integration event and their behavior after chromosomal integration. Post-integration behavior will determine whether the transposable elements being employed currently as primary gene vectors will be useful as gene-tagging and enhancer-trapping agents. The post-integration behavior of existing insect vectors has not been extensively examined. Mos1 is useful as a primary germ-line transformation vector in insects but is inefficiently remobilized in Drosophila melanogaster and Aedes aegypti. Hermes transforms D. melanogaster efficiently and can be remobilized in this species. This element is also useful for creating transgenic A. aegypti, but its mode of integration in mosquitoes results in the insertion of flanking plasmid DNA. Hermes can be remobilized in the soma of A. aegypti and transposes using a common cut-and-paste mechanism; however, the element does not remobilize in the germ line. piggyBac can be used to create transgenic mosquitoes and occasionally integrates using a mechanism other than a simple cut-and-paste mechanism. Preliminary data suggest that remobilization is infrequent. Minos also functions in mosquitoes and, like the other gene vectors,appears to remobilize inefficiently following integration. These results have implications for future gene vector development efforts and applications.
Transport mechanisms of diuresis in Malpighian tubules of insects
Authors: Beyenbach Klaus W. 
Published: September 2003

SUMMARYWe have studied Malpighian tubules of Aedes aegypti using a variety of methods: Ramsay fluid secretion assay, electron probe analysis of secreted fluid, in vitro microperfusion and two-electrode voltage clamp. Collectively, these methods have allowed us to elucidate transepithelial transport mechanisms under control conditions and in the presence of diuretic peptides. Mosquito natriuretic peptide (MNP), a corticotropin-releasing factor (CRF)-like diuretic peptide, selectively increases transepithelial secretion of NaCl and water, meeting the NaCl loads of the blood meal. The intracellular messenger of MNP is cAMP, which increases the Na+ conductance and activates the Na+/K+/2Cl--cotransporter in the basolateral membrane of principal cells. Leucokinin non-selectively increases transepithelial NaCl and KCl secretion, which may deal with hemolymph volume expansions or reduce the flight pay load upon eclosion from the aquatic habitat. The non-selective NaCl and KCl diuresis stems from the increase in septate junctional Cl- conductance activated by leucokinin using Ca2+ as second messenger. Fundamental to diuretic mechanisms are powerful epithelial transport mechanisms in the distal segment of the Malpighian tubules, where transepithelial secretion rates can exceed the capacity of mammalian glomerular kidneys in the renal turnover of the extracellular fluid compartment. In conjunction with powerful epithelial transport mechanisms driven by the V-type H+-ATPase, diuretic hormones enable hematophagous and probably also phytophagous insects to deal with enormous dietary loads, thereby contributing to the evolutionary success of insects.
Antimalarial compounds: from bench to bedside
Authors: Olliaro Piero L. , Taylor Walter R. J. 
Published: September 2003

SUMMARYThe emergence and spread of drug-resistant malaria parasites is the major threat to effective malaria control. So far, malaria control has relied heavily on a restricted number of chemically related drugs belonging to either the quinoline or the antifolate groups. Only recently have the artemisinin-type compounds been used widely, predominantly in Southeast Asia. Experience has shown that resistance eventually curtails the life span of antimalarial drugs. If measures are not applied to contain resistance, the investment put into the development of new drugs will be squandered.Current efforts focus, on the one hand, on research into novel compounds with mechanisms of action that are different to the traditionally used drugs,and, on the other hand, on measures to prevent or delay resistance when drugs are introduced. Drug discovery and development are long, risky and expensive ventures. Whilst very few new antimalarial drugs were developed in the last quarter of the 20th century (only four of the nearly 1400 drugs registered worldwide during 1975-1999), various private and public institutions are at work to discover and develop new compounds. Today, the antimalarial pipeline is relatively healthy. Projects are underway at different stages of drug development, from pre-development to registration. However, there is relatively little novelty, as current development projects still rely upon the traditional quinoline, antifolate and, in particular, artemisinin compounds. New structures are expected from the more upstream discovery efforts but it will take time before they become drugs.Therefore, whilst waiting for the drugs of tomorrow, there is a pressing need for immediately available, effective and affordable drugs that will have long life spans. Drug combinations that have independent modes of action are seen as a way of enhancing efficacy while ensuring mutual protection against resistance.Most research work has focussed on the use of artesunate combined with currently used standard drugs, namely mefloquine, amodiaquine,sulfadoxine/pyrimethamine and chloroquine. There is clear evidence that combinations improve efficacy without increasing toxicity. However, the absolute cure rates that are achieved by combinations vary widely and are dependent on the level of resistance of the standard drug. From these studies,further work is underway to produce fixed dose combinations that will be packaged in blister packs. Malaria control programmes need efficacious drugs that can be used with ease by the populations of endemic countries.This review will summarise current antimalarial drug developments and outline recent clinical research that aims to bring artemisinin-based combinations to those that need them most.
Venous leg ulcers after hip replacement
Authors: Mehta J. S. , Nicolaou N. , Kiryluk S. , Fordyce M. J. F. 
Published: September 2003

Venous ulceration is a chronic disabling complication of deep-vein thrombosis. The aim of this study was to estimate the incidence of venous leg ulcers five years or more after total hip replacement (THR) and to investigate some of the clinical features associated with their development. We carried out a postal survey of all patients who had undergone a THR 5 to 12 years previously. Replies from 816 patients showed that 66 (8.1%) had a history of leg ulcers. The prevalence of active ulceration was 2.6% and 43 patients (5.3%) reported developing ulceration since their hip replacement. A clinical review determined that 31 (3.8%) of these were true venous ulcers. The ulcers occurred more commonly on the operated side and developed at a mean of 5.8 years (18 months to 12 years) after the first arthroplasty. A mean of 1.9 arthroplasties (1 to 5) (primary and revision) were carried out before the ulcers appeared. The overall incidence of ulcers was similar to that in the general population.
Experimental study of maleation of polypropylene in various twin‐screw extruder systems
Authors: Chang Dohoon , White James L. 
Published: September 2003

AbstractA range of continuous mixing machines were used as continuous reactors for grafting maleic anhydride onto polypropylene. The machines used were (1) a nonintermeshing modular counterrotating twin‐screw extruder, (2) an intermeshing modular corotating twin‐screw extruder, (3) intermeshing modular counterrotating twin‐screw extruder, and (4) a Kobelco Nex‐T continuous mixer. The grafting reaction of maleic anhydride onto polypropylene and degradation of polypropylene during the grafting reaction were investigated as means for comparing these different machines for reactive extrusion. The influence of processing variables such as screw speed and processing temperature on polymer characteristics also was investigated. Generally, in a comparison of the different machines, the intermeshing counterrotating twin‐screw extruder had the lowest levels of grafted maleic anhydride, whereas the Kobelco Nex‐T continuous mixer under the conditions used had the highest levels of grafted maleic anhydride. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1755–1764, 2003
Ultrasonic oscillations effect on rheological and processing properties of metallocene‐catalyzed linear low density polyethylene
Authors: Wu Hong , Guo Shaoyun , Chen Guangshun , Lin Jia , Chen Wei , Wang Hongtao 
Published: September 2003

AbstractThe effects of ultrasonic oscillations and die materials on die pressure, productivity of extrusion, melt viscosity of metallocene‐catalyzed linear low density polyethylene (mLLDPE), as well as their mechanism were studied in a special ultrasonic oscillations extrusion system developed in our lab. Die materials used in our experiment included steel, brass, and polytetrafluoroethylene (PTFE). The experimental results showed that ultrasonic oscillations as well as die materials have great influence on the rheological and processing behavior of mLLDPE. Ultrasonic oscillations can greatly increase the productivity of mLLDPE melt extruded through different dies, and can decrease the die pressure and the melt viscosity of mLLDPE. Compared with steel or brass die, mLLDPE melt extruded through PTFE die is more sensitive to ultrasonic oscillations. A possible mechanism for the improved processability of mLLDPE is proposed in this article. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1873–1878, 2003
Alcohol consumption and the risk of nosocomial infection in general surgery
Authors: Delgado-Rodríguez M , Mariscal-Ortiz M , Gómez-Ortega A , Martínez-Gallego G , Palma-Pérez S , Sillero-Arenas M , Medina-Cuadros M 
Published: September 2003

Abstract

Background
Alcohol consumption increases community-acquired infections and affects the immune system. The aim of this report was to analyse whether drinking increases the risk of nosocomial infection.

Methods
This was a prospective study of 1505 patients admitted consecutively to a general surgical department. Alcohol consumption was assessed by a structured questionnaire. Postoperative infection was classified using the Centers for Disease Control criteria. Confounding was controlled for by logistic regression analysis, and the results were stratified by gender and drinking pattern.

Results
Most women were light drinkers and no increased risk of postoperative infection was noted. In men, drinking was associated with a lower American Society of Anesthesiologists grade and fewer co-morbidities. Heavy alcohol consumption (more than 108 g/day) in men increased the rate of all-site nosocomial infection (adjusted odds ratio (OR) 2·51, 95 per cent confidence interval (c.i.) 1·06 to 5·96) and the rate of in-hospital surgical-site infection (SSI) (adjusted OR 2·16, 95 per cent c.i. 0·84 to 5·58). An intake of above 72 g/day increased the rate of lower respiratory tract infection (adjusted OR 5·22, 95 per cent c.i. 1·04 to 26·2). Alcohol consumption was not related to the rate of SSI after hospital discharge. When drinking was limited to weekends, there was no relationship with nosocomial infection.

Conclusion
Heavy alcohol consumption increased the risk of nosocomial infection in men who underwent general surgical procedures.
Effect of endoscopic ultrasonography on the management of 100 consecutive patients with oesophageal and junctional carcinoma
Authors: Preston S R , Clark G W B , Martin I G , Sue Ling H M , Harris K M 
Published: September 2003

Abstract

Background
Endoscopic ultrasonography (EUS) offers very accurate tumour and node staging information for oesophagogastric cancer. The aim was to determine whether the addition of EUS directly influenced the definitive management plan for individual patients.

Methods
Personal and staging information from 100 consecutive patients with carcinoma of the oesophagus or oesophagogastric junction were summarized and blinded. Three consultant oesophagogastric surgeons independently made a management decision for each patient, in the presence and absence of the EUS data. All scored their perceived value of the EUS staging data for each patient.

Results
EUS was deemed useful in 63–87 per cent of patients and its addition resulted in an increased number of concordant management plans (from 53 to 62 per cent), and increased agreement between surgeons. The greatest change in concordant management was an increased referral of patients for non-surgical palliation.

Conclusion
The addition of EUS to the staging of patients with oesophageal and oesophagogastric junction cancer significantly altered the management strategy for some of these patients.
Gastrointestinal stromal tumours
Authors: Connolly E M , Gaffney E , Reynolds J V 
Published: September 2003

Abstract

Background
Gastrointestinal stromal tumours (GISTs), previously classified as benign or malignant smooth muscle tumours, are the most common mesenchymal tumours of the gastrointestinal tract. GISTs express a growth factor receptor with tyrosine kinase activity, termed KIT. Mutations of KIT are common in malignant GISTs and lead to constitutional activation of tyrosine kinase function, which causes cellular proliferation and resistance to apoptosis. GISTs are notoriously unresponsive to chemotherapy and, until the recent introduction of the KIT inhibitor imatinib, there has been no effective therapy for advanced, metastatic disease.

Methods
A Medline literature search was preformed to locate all articles relating to gastrointestinal tumours, GISTs, KIT and imatinib.

Results and conclusions
The 5-year survival rate after complete resection of GISTs is approximately 50 per cent. The median duration of survival for patients with a metastatic GIST is approximately 20 months, and 9–12 months for patients with local recurrence. Phase II trials have investigated the effect of imatinib on irresectable or metastatic GISTs. In these trials more than 50 per cent of patients responded to imatinib within a few months and approximately 12 per cent had disease progression. Uptake of [18F]fluoro-2-deoxy-d-glucose demonstrated by positron emission tomography has been found to be reduced after starting imatinib. The potential for cure and the optimal length of treatment is currently unknown. Imatinib is the first effective systemic therapy for metastatic and locally irresectable GISTs. Large multi-institutional clinical trials to investigate the efficacy of imatinib as adjuvant or neoadjuvant therapy for GISTs are now required.
Role of peritoneal mesothelial cells in peritonitis
Authors: Yao V , Platell C , Hall J C 
Published: September 2003

Abstract

Background
Peritoneal mesothelial cells have a remarkable capacity to respond to peritoneal insults. They generate an intense biological response and play an important role in the formation of adhesions. This review describes these activities and comments on their relationship to surgical drainage, peritoneal lavage and laparostomy in the management of patients with peritonitis.

Methods and results
Material was identified from previous review articles, references cited in original papers and a Medline search of the literature. The peritoneal mesothelium adapts to peritonitis by facilitating the clearance of contaminated fluid from the peritoneal cavity and inducing the formation of fibrinous adhesions that support the localization of contaminants. In addition, the fluid within the peritoneal cavity is a battleground in which effector mechanisms generated with the involvement of peritoneal mesothelial cells meet the contaminants. The result is a complex mix of cascading processes that have evolved to protect life in the absence of surgery.

Conclusion
Future advances in the management of patients with severe peritonitis may depend upon molecular strategies that modify the activity of peritoneal mesothelial cells.
Macaque monkey retrosplenial cortex: II. Cortical afferents
Authors: Kobayashi Yasushi , Amaral David G. 
Published: September 2003

AbstractWe investigated the cortical afferents of the retrosplenial cortex and the adjacent posterior cingulate cortex (area 23) in the macaque monkey by using the retrograde tracers Fast blue and Diamidino yellow. We quantitatively analyzed the distribution of labeled neurons throughout the cortical mantle. Injections involving the retrosplenial cortex resulted in labeled neurons within the retrosplenial cortex and in areas 23 and 31 (∼78% of the total labeled cells). In the remainder of the cortex, the heaviest projections originated in the hippocampal formation, including the entorhinal cortex, subiculum, presubiculum, and parasubiculum. The parahippocampal and perirhinal cortices also contained many labeled neurons, as did the prefrontal cortex, mainly in areas 46, 9, 10, and 11, and the occipital cortex, mainly area V2. Injections in area 23 also resulted in numerous labeled cells in the posterior cingulate and retrosplenial regions (∼67% of total labeled cells). As in the retrosplenial cortex, injections of area 23 led to many labeled neurons in the frontal cortex, although most of these cells were in areas 9 and 46. Larger numbers of retrogradely labeled cells were also distributed more widely in the posterior parietal cortex, including areas 7a, 7m, LIP, and DP. There were some labeled cells in the parahippocampal cortex. These connections are consistent with the retrosplenial cortex acting as an interface between the working memory functions in the prefrontal areas and the long‐term memory encoding in the medial temporal lobe. The posterior cingulate cortex, in contrast, may be more highly associated with visuospatial functions. J. Comp. Neurol. 466:48–79, 2003. © 2003 Wiley‐Liss, Inc.
MyD88 is essential for clearance of Leishmania major: possible role for lipophosphoglycan and Toll‐like receptor 2 signaling
Authors: de Veer Michael J. , Curtis Joan M. , Baldwin Tracey M. , DiDonato Joseph A. , Sexton Adrienne , McConville Malcolm J. , Handman Emanuela , Schofield Louis 
Published: September 2003

AbstractLeishmania major is an obligate intracellular eukaryotic pathogen of mononuclear phagocytes. Invasive promastigotes gain entry into target cells by receptor‐mediated phagocytosis, transform into non‐motile amastigotes and establish in the phagolysosome. Glycosylphosphatidylinositol‐anchored lipophosphoglycan (LPG) is a virulence factor and a major parasite molecule involved in this process. We observed that mice lacking the Toll‐like receptor (TLR) pathway adaptor protein MyD88 were more susceptible to infection with L. major than wild‐type C57BL/6 mice, demonstrating a central role for this innate immune recognition pathway in control of infection, and suggesting that L. major possesses a ligand for TLR. We sought to identify parasite molecules capable of activating the protective Toll pathway, and found that purified Leishmania LPG, but not other surface glycolipids, activate innate immune signaling pathways via TLR2. Activation of cytokine synthesis by LPG required the presence of the lipid anchor and a functional MyD88 adaptor protein. LPG also induced the expression of negative regulatory pathways mediated by members of thesuppressors of cytokine signaling family SOCS‐1 and SOCS‐3. Thus, the Toll pathway is required for resistance to L. major and LPG is a defined TLR agonist from this important human pathogen.
HLA class I‐restricted recognition of an HIV‐derived epitope peptide by a human T cell receptor α chain having a Vδ1 variable segment
Authors: Ueno Takamasa , Tomiyama Hiroko , Fujiwara Mamoru , Oka Shinichi , Takiguchi Masafumi 
Published: September 2003

AbstractA subset of human peripheral α β T cells have been shown to express TCR α chains containing Vδ1 segments, although what antigens the Vδ1+ α β T cells recognize via these TCR is not known yet. We eventually established a human CD8 T cell clone that expressed α β TCR and Vδ1 antigens. Corroboratively, a unique in‐frame Vδ1.1JαCα transcript was found in the clone. The clone showed cytotoxic activity and IFN‐γ production towards cells expressing HLA‐B*3501 pulsed with an HIV Pol‐derived epitope peptide (IPLTEEAEL). By flow‐cytometric analysis ex vivo using an HLA‐B*3501 tetramer, a fraction of Vδ1+CD8+tetramer+ cells was found in peripheral lymphocytes of an HIV‐infected patient, indicating the existence of HLA‐restricted and HIV‐specific Vδ1+ CD8 T cells in vivo. Moreover, retrovirus‐mediated transfer of the TCR‐encoding genes into TCR‐negative hybridoma cells showed that the transduced cells were stained by the tetramer and were activated in response to the Pol peptide, further confirming the ligand specificity of the TCR. Together, these results clearly demonstrate that Vδ1+ α β TCR are restricted to engaging peptide antigens in the context of classical MHC class I molecules, highlighting the difference in the ligand specificity between Vδ1+ α β TCR and Vδ1+ γ δ TCR.