bluuebunny/crossref_metadata_2025 huggingface dataset:
Recommendations for postmarketing surveillance studies in haemophilia and other bleeding disorders
Authors: Lassila R. , Rothschild C. , de Moerloose P. , Richards M. , Perez R. , Gajek H. ,   on behalf of the European Haemophilia Therapy Standardisation Board (EHTSB)
Published: July 2005

Summary.  Prospective surveillance studies to monitor drug safety in the postapproval period are rarely employed systematically, although they are of greatest value for caregivers, drug users and regulatory authorities. Safety issues have affected not only conventional pharmaceuticals, but also especially coagulation factors in haemophilia treatment. The reputation of postmarketing surveillance (PMS) studies has been questionable, mainly due to their misuse to solicit prescriptions. Other weaknesses include inappropriate design, lack of standardized observation, limited follow‐up periods, absence of rigour in identifying potential adverse drug effects, and infrequent publication. Although well‐designed clinical trials represent the gold standard for generating sound clinical evidence, a number of aspects would make PMS studies valuable, if properly conducted. One of their main advantages is broader inclusion, and absence of an ‘experimental’ design. Lack of proper guidelines, and standardization may constitute a reason for the generally low quality of PMS studies. This paper proposes guidelines for haemophilia‐specific PMS studies, in order to improve the acceptance of a basically valuable tool. In the absence of consistent regulatory guidance it will be especially important that the design and supervision of PMS studies involves physicians from the beginning. This will not only make such studies more scientifically relevant, but also help to implement them into daily clinical practice. Specifically in haemophilia, PMS studies may provide valuable data on clinical outcomes, or Quality of Life, which is of great importance when considering adequate standards of care in haemophilia patients.
A New family with frontotemporal dementia with intronic 10+3 splice site mutation in the tau gene: neuropathology and molecular effects
Authors: Neumann M. , Mittelbronn M. , Simon P. , Vanmassenhove B. , De Silva R. , Lees A. , Klapp J. , Meyermann R. , Kretzschmar H. A.
Published: July 2005

Mutations in the tau gene cause familial frontotemporal dementia with parkinsonism linked to chromosome 17 characterized by filamentous tau protein deposits. Here we describe the clinical and neuropathological features of a case from a newly identified family with an intron 10+3‐splice site mutation in the tau gene. The proband presented with severe personality changes and stereotyped speech followed by parkinsonian symptoms. He died at age 56 after a disease duration of approximately 6 years. At autopsy, there was marked frontotemporal degeneration with abundant tau‐immunoreactive neuronal and glial inclusions widespread in the cortex and brainstem. RT‐PCR analysis revealed a 3.7‐fold increase of tau transcripts with exon 10, resulting in an 1.7‐fold higher expression level of 4‐repeat tau isoforms in soluble tau fractions when compared to control brains and exclusively 4‐repeat tau isoforms in the sarcosyl‐insoluble tau fractions. In accordance with the hypothesis that the overexpression leads to saturation of microtubule binding sites and an increase of unbound 4‐repeat tau isoforms which assemble into filaments, the neuronal and glial inclusions in this case were exclusively composed of 4‐repeat tau isoforms. The clinical and neuropathological data of this family are compared with  results  from  the  two  other  published  families  with the intron 10 + 3 mutation, the MSTD and the SOT 254 family.
Indoleamine 2,3 dioxygenase and quinolinic acid Immunoreactivity in Alzheimer's disease hippocampus
Authors: Guillemin G. J. , Brew B. J. , Noonan C. E. , Takikawa O. , Cullen K. M.
Published: July 2005

The present immunohistochemical study provides evidence that the kynurenine pathway is up‐regulated in Alzheimer's disease (AD) brain, leading to increases in the excitotoxin quinolinic acid (QUIN). We show that the regulatory enzyme of the pathway leading to QUIN synthesis, indoleamine 2,3 dioxygenase (IDO) is abundant in AD compared with controls. In AD hippocampus, both IDO‐ and QUIN‐immunoreactivity (‐IR) was detected in cortical microglia, astrocytes and neurones, with microglial and astrocytic expression of IDO and QUIN highest in the perimeter of senile plaques. QUIN‐IR was present in granular deposits within the neuronal soma of AD cortex and was also seen uniformly labelling neurofibrillary tangles. Our data imply that QUIN may be involved in the complex and multifactorial cascade leading to neuro‐degeneration in AD. These results may open a new therapeutic door for AD patients.
Impact of rising tropospheric ozone on potato: effects on photosynthesis, growth, productivity and yield quality
Authors: VANDERMEIREN K. , BLACK C. , PLEIJEL H. , DE TEMMERMAN L.
Published: July 2005

In view of its importance for human nutrition, the European Commission funded a collaborative research programme (1998–99) to evaluate the impact of future increases in atmospheric ozone (O3) and carbon dioxide (CO2) concentrations on yield and tuber quality in potato (Solanum tuberosum L.). This was the first large‐scale open‐top chamber project to provide field‐based data spanning a wide range of European climatic conditions and ozone concentrations for a widely used cultivar, cv. Bintje. Intensive measurements of physiological and developmental effects were made throughout crop growth to improve the mechanistic understanding of the processes involved. Analysis of the experimental results and modelling work based on the extensive database revealed that the increasing tropospheric O3 concentrations predicted under future climatic scenarios in Europe are likely to reduce tuber yield in potato. However, season‐long exposure to elevated O3 had both beneficial and detrimental effects on tuber quality. Most of the significant physiological and growth effects occurred during the later stages of crop development, when elevated O3 reduced photosynthesis and promoted senescence. The observed changes in the quality and nutritional attributes of tubers, such as decreased content of reducing sugars and increased nitrogen concentrations, may be attributable to reduced carbohydrate allocation.
Singlet oxygen and photo‐oxidative stress management in plants and algae
Authors: LEDFORD HEIDI K. , NIYOGI KRISHNA K.
Published: July 2005

Photosynthetic organisms constantly face the threat of photo‐oxidative stress from fluctuating light conditions and environmental stress. Plants and algae have developed an array of defences to protect the chloroplast from reactive oxygen species. Genetic and physiological studies have shown that antioxidant responses are important to high‐light acclimation, both by directly scavenging or quenching reactive oxygen intermediates and by contributing reducing power for alternative electron transport pathways and excess energy dissipation. At present, the signalling events leading to up‐regulation of antioxidant defences in high light remain a mystery. Recent advances toward understanding acclimation to oxidative stress in both photosynthetic and non‐photosynthetic model organisms may illuminate how plants and algae respond to high‐light stress. Although the role of hydrogen peroxide in high‐light acclimation has been investigated, less is known about responses to singlet oxygen, a form of reactive oxygen that poses a significant threat specifically to photosynthetic organisms. This review will discuss some intriguing new findings in that area, focusing on recent findings regarding the nature of singlet‐oxygen responses in the chloroplast.
Chordoma: Radiological–pathological correlation
Authors: Maclean FM , Soo MYS , Ng T
Published: July 2005

This review correlates the imaging findings and histological appearances seen in chordomas in a series of patients presenting at our institution, together with a published literature review. A parallel presentation of photographs of imaging findings and microscopic histological findings is made, with the aim being to enhance recognition of this uncommon but clinically significant entity.
Intra‐abdominal splenosis: How clinical history and imaging features averted an invasive procedure for tissue diagnosis
Authors: Lui EHY , Lau KKP
Published: July 2005

A 47‐year‐old man with a past history of splenectomy was referred for biopsy of a liver lesion. A subsequent 99mtechnetium heat‐damaged red cell scan helped make the diagnosis of splenosis and averted a biopsy procedure.
Reactive oxygen species are essential mediators in antigen presentation by Kupffer cells
Authors: Maemura Kosei , Zheng Qizhi , Wada Tatehiko , Ozaki Michitaka , Takao Sonshin , Aikou Takashi , Bulkley Gregory B , Klein Andrew S , Sun Zhaoli
Published: July 2005

Kupffer cells (KC) act as APC in the liver and play a major role in the clearance of gut‐derived antigens and pathogens entering the liver with portal venous blood. Antigen presentation by KC has been implicated in regulation of the local and systemic immune responses. In this study, modulation of KC antigen presentation by antioxidants and the role of reactive oxygen species (ROS) as essential mediators of antigen presentation in KC were investigated. Co‐culture of KC with ovalbumin (OVA) antigens resulted in upstream intracellular endogenous ROS generation and increased expression of MHC class II and costimulator molecules, and consequent OVA‐specific CD4+ T‐cell proliferation in response to antigen presentation by KC. Scavenging of KC ROS by antioxidants, or blocking of KC ROS generation by specific inhibitors of NADPH oxidase and/or xanthine oxidase, or by specific inhibitors of the mitochondrial electron transport chain, significantly decreased OVA‐specific T‐cell proliferation in response to antigen presentation by KC. Increased expression of MHC class II and costimulatory molecules in KC pulsed with OVA antigens was blocked by inhibiting ROS generation enzymatically. Intracellular endogenous ROS generation during antigen processing may therefore provide essential secondary signalling for KC antigen presentation.
Immunity to melanoma mediated by 4‐1BB is associated with enhanced activity of tumour‐infiltrating lymphocytes
Authors: Ju Seong‐A , Lee Sang‐Chul , Kwon Tae‐Hyoung , Heo Sook‐Kyoung , Park Sang‐Min , Paek Ha‐Na , Suh Jae‐Hee , Cho Hong Rae , Kwon Byungsuk , Kwon Byoung S , Kim Byung‐Sam
Published: July 2005

4‐1BB costimulates T cells to carry out effector functions such as eradication of established tumours. 4‐1BB (CD137) is a member of the TNF receptor family, and its triggering by either 4‐1BB ligand or antibody ligation induces T‐cell activation and growth. We analysed tumour‐infiltrating lymphocytes (TIL) in the experimental B16F10 melanoma model to determine the mechanisms involved in 4‐1BB‐mediated tumour suppression. 4‐1BB+/+ mice survived longer than 4‐1BB–/– mice, and survival was further prolonged by triggering 4‐1BB with an agonistic mAb. The number of metastatic B16F10 colonies in the lung was much greater in 4‐1BB–/– mice than in their 4‐1BB+/+ littermates. Administration of agonistic anti‐4‐1BB mAb increased the number of TIL in the tumour masses in the lungs of 4‐1BB+/+ mice. The numbers of CD4+ T, CD8+ T and CD11b+ TIL increased in these mice. Anti‐4‐1BB mAb induced not only CD8+ 4‐1BB+ T cells but also a CD8+ IFN‐γ+ T‐cell population. B16F10 cells from the lungs of anti‐4‐1BB‐treated mice showed enhanced expression of MHC class Ι and II antigens compared with the same cells from control IgG‐treated mice. Thus, the increase in number of CD8+ T cells and enhanced MHC Ι and II expression in B16F10 cells that result from augmented IFN‐γ production in response to anti‐4‐1BB mAb may lead to suppression of tumour growth and metastasis.
Antibody blockade of Thy‐1 (CD90) impairs mouse cytotoxic T lymphocyte induction by anti‐CD3 monoclonal antibody
Authors: Haeryfar SM Mansour , Conrad David M , Musgrave Bruce L , Hoskin David W
Published: July 2005

Thy‐1 (CD90) expressed by mouse T cells is known to have signal transducing properties, but the ability of Thy‐1 to enhance cytotoxic T lymphocyte (CTL) development is not well understood. Here we show that stimulation of mouse T cells with monoclonal antibodies (mAb) to CD3, CD28 and Thy‐1 (clone G7), which were coimmobilized on polystyrene microbeads, resulted in a greater proliferative response than stimulation with only anti‐CD3 and anti‐CD28 mAb, indicating that Thy‐1 cross‐linking enhanced T cell receptor/CD28‐driven T cell activation. Consistent with this finding, Thy‐1 blockade with a soluble nonactivating anti‐Thy‐1 mAb (clone 30‐H12) inhibited anti‐CD3‐induced proliferation of CD4+ and CD8+ T cells, and the induction of cytotoxic effector cells in a dose‐dependent fashion. Interleukin‐2 synthesis and CD25 expression were also impaired by Thy‐1 blockade. The inhibitory effect involved a defect at or before the level of protein kinase C activation because the addition of phorbol ester ablated the anti‐Thy‐1‐mediated inhibition of anti‐CD3‐induced T cell activation. The CTL that were induced in the presence of blocking anti‐Thy‐1 mAb adhered to target cells but showed reduced expression of granzyme B and perforin. In contrast, Fas ligand expression and function was not affected by Thy‐1 blockade. We conclude that Thy‐1 signalling promotes the in vitro generation of CTL that kill in a granule‐dependent fashion.
Human antibodies to the polymorphic block 2 domain of the Plasmodium falciparum merozoite surface protein 1 (MSP‐1) exhibit a highly skewed, peptide‐specific light chain distribution
Authors: Jouin Hélène , Garraud Olivier , Longacre Shirley , Baleux Françoise , Mercereau‐Puijalon Odile , Milon Geneviève
Published: July 2005

Antibodies to polymorphic block 2 of the Plasmodium falciparum merozoite surface protein 1 (MSP‐1) present a paradoxical association with acquired protection against clinical malaria, while showing restricted and fixed specificity, reminiscent of antigenic sin. We report here that these antibodies present a highly imbalanced, peptide‐specific light chain distribution. This was not observed with several other parasite‐derived peptides or antigens. These data point to a skewed immune response to MSP‐1 block 2 that is constrained both in specificity and chain usage. This is the first report of a biased response to polymorphic epitopes of a surface antigen in malaria parasites.
Tumor‐associated carbohydrate antigens: A possible avenue for cancer prevention
Authors: Xu Yanfei , Sette Alessandro , Sidney John , Gendler Sandra J , Franco Alessandra
Published: July 2005

Here we examine the use of glycopeptides containing tumour‐associated carbohydrate antigens (TACA) as potential preventive vaccines for carcinomas. Our recent results suggest that CD8+ T cells (CTL) are capable of recognizing TACA in a conventional class I MHC‐restricted fashion. The Thomsen–Friedenreich antigen (TF), a disaccharide, and Tn, its immediate precursor, are TACA largely expressed in carcinomas. TF and Tn can be successfully used as Th‐independent vaccines when conjugated to designer peptides with optimal binding affinity for class I MHC molecules. TF‐ and Tn‐specific CTL generated using this strategy are capable of recognizing TACA‐expressing tumours in vitro, suggesting that glycopeptides are as effectively presented by class I MHC molecules as non‐glycosylated peptides. Because the exact sequences of endogenously synthesized glycopeptides are unknown, the TACA‐specific T cell repertoire elicited by carbohydrate‐based vaccines is assumed to be degenerate. Here we report that mice genetically manipulated to develop TACA‐expressing mammary tumours are not tolerant to glycopeptide vaccination. Moreover, we tested the immunogenicity of designer glycopeptides capable of binding multiple HLA alleles as a novel approach for the development of vaccines potentially useful for vaccination of a large fraction of the general population. Our results have suggested that CTL derived from normal donors respond with high efficiency to glycopeptides in vitro, opening a new avenue for the design of prospective vaccines for cancer prevention.
In pursuit of xenoreactive antibodies: Where has it gotten us?
Authors: Parker William , Lesher Aaron P
Published: July 2005

Numerous studies have aimed to overcome the barrier to xenotransplantation posed by xenoreactive antibodies and the antigens they recognize. Whether this work will eventually lead to the widespread clinical application of xenotransplantation remains unknown. However, the benefits of this research are already substantial, with research leading to dramatic new developments in fields other than xenotransplantation. Our understanding of natural immunity, particularly the nature and function of natural antibodies, has taken quantum leaps forward, with far‐reaching implications. Our improved understanding of the immune response to xenografts has proven invaluable in the characterization of the human immune reaction to commonly used biological therapeutics of xenogeneic origin. Our understanding of cell surface carbohydrates and our ability to modify these carbohydrates in living animals has advanced substantially, with implications for diseases such as cancer and autoimmunity. With this in mind, it is argued that continued work in xenotransplantation is of great value, not only because of the great potential benefits of xenotransplantation, but also because of the more certain benefits that arise from setting our sights on a difficult challenge.
Carbohydrate vaccines as immunotherapy for cancer
Authors: Slovin Susan F , Keding Stacy J , Ragupathi Govind
Published: July 2005

Carbohydrates have established themselves as the most clinically relevant antigens of those tested and subsequently developed for vaccines against infectious diseases. However, in cancer patients, many of the defined carbohydrate antigens are really altered ‘self’ antigens and for unclear reasons, the body does not react to them immunologically. Although these self antigens have been found to be potentially suitable targets for immune recognition and killing, the development of vaccines for cancer treatment is actually more challenging compared with those for infectious diseases mainly because of the difficulty associated with breaking the body's immunological tolerance to the antigen. These antigens lack the inherent immunogenicity associated with bacterial antigens and, therefore, methods to enhance immunological recognition and induction of immunity in vivo are under investigation. These include defining the appropriate tumour‐associated antigen, successfully synthesizing the antigen to mimic the original molecule, inducing an immune response, and subsequently enhancing the immunological reactivity so that all components can work together. This has been successfully accomplished with several glycolipid and glycoprotein antigens using carriers such as keyhole limpet haemocyanin (KLH) together with a saponin adjuvant, QS‐21. Not only can high titre IgM and IgG antibodies be induced, which are specific for the antigen used for immunization, but the antibodies can mediate complement lysis. The approaches for synthesis, conjugation, clinical administration and immunological potential are discussed.
Altered glycosylation of proteins produced by malignant cells, and application for the diagnosis and immunotherapy of tumours
Authors: Kobata Akira , Amano Junko
Published: July 2005

Most secretory and membrane‐bound proteins produced by mammalian cells contain covalently linked sugar chains. Alterations of the sugar chain structures of glycoproteins have been found to occur in various tumours. Because the sugar chains of glycoproteins are essential for the maintenance of the ordered social behaviour of differentiated cells in multicellular organisms, alterations to the sugar chains are the molecular basis of abnormal social behaviours in tumour cells, such as invasion into the surrounding tissues and metastasis. In this review, the structure and enzymatic basis of typical alterations of the N‐linked sugar chains, which are found in various tumours, are introduced. These data are useful for devising diagnostic methods and immunotherapies for the clinical treatment of tumours. Three β‐N‐acetylglucosaminyltransferases, GnT‐III, ‐IV and ‐V, play roles in the structural alteration of the complex‐type sugar chains in various tumours. In addition, transcriptional changes in various glycosyltransferases, together with the transporters of sugar nucleotides and sulfate, which are responsible for the formation of the outer chain moieties of complex‐type sugar chains, are the keys to inducing the alterations.
MEMBRANE MICRODOMAIN SIGNALLING: LIPID RAFTS IN BIOLOGY AND MEDICINE
Authors: Jessup Wendy
Published: July 2005

Immunology and Cell Biology (2005) 83, 449; doi:10.1111/j.1440‐1711.2005.01355.x
Electrodermal predictors of functional outcome and negative symptoms in schizophrenia
Authors: Schell Anne M. , Dawson Michael E. , Rissling Anthony , Ventura Joseph , Subotnik Kenneth L. , Gitlin Michael J. , Nuechterlein Keith H.
Published: July 2005

The ability of electrodermal variables to predict negative symptoms and functional outcome over a 1‐year period in schizophrenia was investigated in 78 young, recent‐onset outpatients. Patients were stabilized on standardized medication and largely free of psychotic symptoms. Higher levels of both tonic (skin conductance level, nonspecific skin conductance response rate) and phasic (number of skin conductance orienting responses) activity were associated with more negative symptoms and with a combination of poorer social and occupational outcome at 1‐year follow‐up. This pattern was seen in both male and female patients, and in older and younger patients. Results are interpreted as suggesting that high levels of arousal and overreactivity to the environment may interfere with efficient cognitive processing in schizophrenia, contributing to poor outcome, and that negative symptoms might partially serve as a means of coping with overarousal.
A PCR‐Based Survey on Phytomonas (Euglenozoa+Trypanosomatidae) in Phytophagous Hemipterans of the Amazon Region
Authors: GODOI MARA M. I. , SERRANO MYRNA G. , TEIXEIRA MARTA M. G. , CAMARGO ERNEY P.
Published: July 2005

ABSTRACT. We have surveyed 244 hemipterans from Western Brazilian Amazônia for the presence of trypanosomatids and identification of members of the genus Phytomonas. Examination by phase microscopy of squashes of insect salivary glands (SG) and digestive tubes (DT) revealed that 44% (108/244) of insects from seven families harbored trypanosomatids. Infections were 5 times more frequent in Coreidae than in all other families together. Smears of SG and DT of the dissected insects were fixed on glass slides with methanol and stained with Giemsa for morphological analysis. DNA was recovered from these preparations and submitted to a PCR assay that permitted amplification of all trypanosomatid genera using primers of conserved sequences flanking a segment of the spliced leader (SL) gene. Upon PCR amplification of the recovered DNA, amplicons were hybridized with an oligonucletide probe (SL3′) complementary to a SL intron sequence specific for flagellates of the genus Phytomonas. Among the trypanosomatid‐positive insects, 38.8% harbored Phytomonas spp., corresponding to an overall Phytomonas prevalence of 17.1% among phytophagous bugs, their putative vectors. Since many Phytomonas are pathogenic in plants, this high prevalence in their vectors emphasizes the permanent risk of exposure to disease by native and cultured plants of the Amazon region.
Ecology, Development and Pathogenicity of Buddenbrockia plumatellae Schröder, 1910 (Myxozoa, Malacosporea) (syn. Tetracapsula bryozoides) and Establishment of Tetracapsuloides n. gen. for Tetracapsula bryosalmonae
Authors: CANNING ELIZABETH U. , TOPS SYLVIE , CURRY ALAN , WOOD TIMOTHY S. , OKAMURA BETH
Published: July 2005

ABSTRACT. Buddenbrockia plumatellae, an enigmatic worm‐like myxozoan, was observed as continuously writhing free and attached ‘worms’ and as free mature spores in the coelom of the freshwater bryozoans Plumatella fungosa, Hyalinella punctata, and Fredericella sp. ‘Worm’ numbers could double every three days. ‘Worms’ and spores could be expelled from colonies by external pressure. Some mature ‘worms’ exited actively, entraining release of free spores, and gradually ceased movement outside the host. Bryozoans sealed off infected regions of the colony. Infected colonies grew slowly, produced no statoblasts, and eventually regressed and died. Transmission was not achieved and prevalence was low. Electron microscopy of ‘worms’ revealed a single layer of mural cells on a fibrous basal lamina overlying four longitudinal muscle blocks and an inner sheet of two types of proliferating cells, an organization indicative of the bilaterian ancestry of the Myxozoa. Primary type A cells were attached directly by striated tubules to mural cells at positions between muscle blocks. Secondary type A cells had a secretory function. Type B cells underwent meiosis and subsequently developed to typical malacosporean myxozoan spores filling the internal cavity of the ‘worms’. External tubes were formed during capsulogenesis in ‘worms’ from Fredericella sp. Tetracapsula bryozoides is synonymised with Buddenbrockia plumatellae and a new genus is proposed for Tetracapsula bryosalmonae.
In Vitro Leishmanicidal Activity of a Monoclonal Antibody mimicking a Yeast Killer Toxin
Authors: SAVOIA DIANELLA , AVANZINI CLAUDLO , CONTI STEFANIA , MAGLIANI VALTER , FRAZZI RAFFAELE , POLONELLI UCIANO
Published: July 2005

ABSTRACT. The microbicidal effect of a monoclonal antiidiotypic antibody, mimicking the activity of a yeast killer toxin, characterized by a wide antimicrobial spectrum, has been evaluated in vitro against two relevant species of protozoan parasites, Leishmania major and Leishmania infantum. The antiidiotypic antibody exerted a significant and dose‐dependent antileishmanial activity against parasite promastigotes in comparison to an irrelevant isotype‐matched monoclonal antibody. This is the first demonstration that an antibody, which had been already shown to be fungicidal and bactericidal, may also exert a direct microbicidal activity against protozoa.
Heparan Sulfate Proteoglycans Mediate the Invasion of Cardiomyocytes by Trypanosoma cruzi
Authors: CALVET CLAUDIA M. , TOMA LENY , DE SOUZA FERNANDA ROCHA , DE MEIRELLES MARIA DE NAZARETH S.L. , PEREIRA MIRIAN CLAUDIA S.
Published: July 2005

ABSTRACT. Cytoadherence is an important step for the Invasion of a mammalian host cell by Trypanosoma cruzi. Cell surface macromolecules are implicated in the T. crazi‐cardiomyocyte recognition process. Therefore, we investigated the role of cell surface proteoglycans during this invasion process and analyzed their expression after the parasite infected the target cells. Treatment of trypomastigote forms of T. cruzi with soluble heparan sulfate resulted in a significant Inhibition in successful invasion, while chondroitin sulfate had no effect. Removal of sulfated glycoconjugates from the cardiomyocyte surface using glycosaminoglycan (GAG) lyases demonstrated the specific binding of the parasites to heparan sulfate proteoglycans. Infection levels were reduced by 42% when the host cells were previously treated with heparitinase II. No changes were detected in the expression of GAGs infected cardiomyocytes even after 96 h of infection. Our data demonstrate that heparan sulfate proteoglycans, but not chondroitin sulfate, mediate both attachment and invasion of cardiomyocytes by T. cruzi.
Molecular Cloning and Sequencing of the Merozoite Surface Antigen 2 Gene from Plasmodium falciparum Strain FCC‐l/HN and Expression of the Gene in Mycobacteria1
Authors: ZHENG CHUNFU , XIE PEIMEI , CHEN YATANG
Published: July 2005

ABSTRACT. Strain bacillus Calmette‐Guerin (BCG) of Mycobacterium bovis has been used as a live bacterial vaccine to immunize more than 3 billion people against tuberculosis. In an attempt to use this vaccine strain as a vehicle for protective antigens, the gene encoding merozoite surface antigen 2 (MSA2) was amplified from strain FCC‐l/HN Plasmodium falciparum genome, sequenced, and expressed in M. bovis BCG under the control of an expression cassette carrying the promoter of heat shock protein 70 (HSP70) from Mycobacterium tuberculosis. The recombinant shuttle plasmid pBCG/MSA2 was introduced into mycobacteria by electroporation, and the recombinant mycobacteria harboring pBCG/MSA2 could be induced by heating to express MSA2; the molecular mass of recombinant MSA2 was about 31 kDa. This first report of expression of the full‐length P. falciparum MSA2 gene in BCG provides evidence for use of the HSP70 promoter in expressing a foreign gene in BCG and in development of BCG as a multivalent vectoral vaccine for malaria.
Variety of Serotypes of Paramecium primaurelia: Single Epitopes are Responsible for Immunological Differentiation
Authors: SIMON MARTIN C. , SCHMIDT HELMUT J.
Published: July 2005

Abstract. Paramecium primaurelia expresses three major types of surface antigens. We report here the identification of the gene for serotype S, which completes the sequence data of expressed serotypes of P. primaurelia. The complete open reading frame of surface antigen S was identified using a novel technique, based upon the presence of conservative regions in the non‐coding areas of the multigene family. We were able to isolate the 7194‐bp‐long open reading frame from the macronuclear DNA for Serotype 156S. The corresponding mRNA was detected in the two serotype S‐expressing stocks, 60 and 156, of P. primaurelia, which clarifies that both stocks are using the same S allele. Comparisons of the nucleic acid and the deduced amino‐acid sequence showed high identity to surface antigen 51B of P. tetraurelia, sufficient to cause an immunological cross‐reaction in vivo. Immunologically relevant epitopes in vivo were identified in the central regions of the genes, constructed of nearly perfect tandem repeats.
Effects of Aqueous Extracts from Leaves and Leaf Litter on the Abundance and Diversity of Soil Gymnamoebae in Laboratory Microcosm Cultures
Authors: ANDERSON O. ROGER
Published: July 2005

Abstract. The distribution and abundance of microbiota in soil and litter may be significantly affected by the quality and quantity of localized patches of leaf organic matter. This study examined the relative effects of aqueous extracts of shed autumn leaves from American beech (Fagus grandifolia), sugar maple (Acer saccharum), red oak (Quercus rubra), and white oak (Quercus alba) on the density and diversity of gymnamoebae in laboratory cultures. Overall, the beech leaf extract produced the most growth of gymnamoebae followed by white oak with leaf extracts from maple and red oak producing least growth. Cultures using natural leaf litter from beneath beech trees had higher densities and diversity of gymnamoebae than leaf‐litter cultures from a maple–oak stand. Soil microcosms confirmed that beech leaf extracts produced a higher density of gymnamoeba growth when added to soil cultures compared with maple and oak leaf extracts. Protein content, CHN (carbon and nitrogen content), and pH of the leaf extracts were assayed, but these alone were not sufficiently different to account for the effects. A dilution experiment indicated that some other concentration‐dependent factor in the extract may produce the effects.
Estrogenic agonism and antagonism of the soy isoflavone genistein in uterus, bone and lymphopoiesis in mice
Authors: ERLANDSSON M. C. , ISLANDER U. , MOVERARE S. , OHLSSON C. , CARLSTEN H.
Published: July 2005

The isoflavone genistein (Gen) is a naturally occurring phytoestrogen found in high concentrations in soy. The biological effects of Gen have been extensively studied. The immunomodulating properties of Gen are, however, less well investigated and the results are contradictory. Our aim was to study possible estrogen agonistic and antagonistic properties of Gen in uterus, bone, lymphopoiesis and B‐cell function by comparing effects in castrated and intact female mice, respectively. Oophorectomized (OVX) and sham‐operated mice were treated with s.c. doses of 17β‐estradiol (E2) (0.16 mg/kg), Gen (50 mg/kg), or vehicle (olive oil) as control. Effects on bone mineral density (BMD) were studied using peripheral quantitative computerized tomography, uterine and thymus weights were examined, lymphopoiesis in thymus and bone marrow was analyzed using flow cytometry, and the frequency of immunoglobulin‐producing B cells in bone marrow and spleen was studied using an ELISPOT assay. Gen was clearly antagonizing endogenous estrogen in sham‐operated female mice as shown by inhibiting the uterine weight and by increasing the frequency of B lymphopoietic cells in bone marrow. The only agonistic effect of Gen was shown by increased BMD in OVX mice. Our results are discussed in the context of estrogen receptor biology.
Adherence of Staphylococcus epidermidis to extracellular matrix proteins and effects of fibrinogen‐bound bacteria on oxidase activity and apoptosis in neutrophils
Authors: NILSDOTTER‐AUGUSTINSSON ÅSA , CLAESSON CARINA , LINDGREN PER‐ERIC , LUNDQVIST‐GUSTAFSSON HELEN , ÖHMAN LENA
Published: July 2005

Staphylococcus epidermidis often causes foreign‐body infections such as those associated with hip prostheses, but the underlying pathogenic mechanisms are not fully understood. We performed spectrophotometry to study the ability of S. epidermidis to bind to immobilised fibrinogen, fibronectin, vitronectin, and collagen. The strains were isolated from infected hip prostheses or from normal flora and the well‐known protein‐binding strain Staphylococcus aureus Cowan was used as positive control. We also analysed the interaction between neutrophils and a fibrinogen‐bound prosthesis‐derived strain of S. epidermidisby measuring chemiluminescence to determine the neutrophil oxidative response and binding of annexin V to indicate neutrophil apoptosis. We found that binding of S. epidermidis to extracellular matrix proteins varied under different growth conditions, and that prosthesis isolates adhered better to vitronectin than did strains from normal flora. The oxidative response caused by fibrinogen‐bound S. epidermidis was not above the background level, which was in marked contrast to the distinct response induced by fibrinogen‐associated S. aureus Cowan. Furthermore, fibrinogen‐adhering S. epidermidis retarded neutrophil apoptosis. We conclude that surface‐bound S. epidermidis induces only a weak inflammatory response, which in combination with the ability of the adherent bacteria to retard neutrophil apoptosis may contribute to low‐grade inflammation and loosening of prostheses.
Predicting Transitional Separation Bubbles
Authors: Redford John A. , Johnson Mark W.
Published: July 2005

This paper describes the modifications made to a successful attached flow transition model to produce a model capable of predicting both attached and separated flow transition. This transition model is used in combination with the Fluent CFD software, which is used to compute the flow around the blade assuming that it remains entirely laminar. The transition model then determines the start of transition location and the development of the intermittency. These intermittency values weight the laminar and turbulent boundary layer profiles to obtain the resulting transitional boundary layer parameters. The ERCOFTAC T3L test cases are used to validate the predictions. The T3L blade is a flat plate with a semi-circular leading edge, which results in the formation of a separation bubble the length of which is strongly dependent on the transition process. Predictions were performed for five T3L test cases for differing free-stream turbulence levels and Reynolds numbers. For the majority of these test cases the measurements were accurately predicted.
Experimental Investigation of Vane Clocking in a One and One-Half Stage High Pressure Turbine
Authors: Haldeman Charles W. , Dunn Michael , Barter John W. , Green Brian R. , Bergholz Robert F.
Published: July 2005

Aerodynamic measurements were acquired on a modern single-stage, transonic, high-pressure turbine with the adjacent low-pressure turbine vane row (a typical civilian one and one-half stage turbine rig) to observe the effects of low-pressure turbine vane clocking on overall turbine performance. The turbine rig (loosely referred to in this paper as the stage) was operated at design corrected conditions using the Ohio State University Gas Turbine Laboratory Turbine Test Facility. The research program utilized uncooled hardware in which all three airfoils were heavily instrumented at multiple spans to develop a full clocking dataset. The low-pressure turbine vane row (LPTV) was clocked relative to the high-pressure turbine vane row (HPTV). Various methods were used to evaluate the influence of clocking on the aeroperformance (efficiency) and the aerodynamics (pressure loading) of the LPTV, including time-resolved and time-averaged measurements. A change in overall efficiency of approximately 2–3% due to clocking effects is demonstrated and could be observed using a variety of independent methods. Maximum efficiency is obtained when the time-average surface pressures are highest on the LPTV and the time-resolved surface pressure (both in the time domain and frequency domain) show the least amount of variation. The overall effect is obtained by integrating over the entire airfoil, as the three-dimensional (3D) effects on the LPTV surface are significant. This experimental data set validates several computational research efforts that suggested wake migration is the primary reason for the perceived effectiveness of vane clocking. The suggestion that wake migration is the dominate mechanism in generating the clocking effect is also consistent with anecdotal evidence that fully cooled engine rigs do not see a great deal of clocking effect. This is consistent since the additional disturbances induced by the cooling flows and∕or the combustor make it extremely difficult to find an alignment for the LPTV given the strong 3D nature of modern high-pressure turbine flows.
Laminar Natural Convection Heat Transfer From a Vertical Baffled
Plate Subjected to a Periodic Oscillation
Authors: Zhang Xinrong , Maruyama Shigenao , Yamaguchi Hiroshi
Published: July 2005

The problem of laminar natural convection on a vertical baffled plate subjected to a periodic oscillation is investigated numerically. Of particular interest of this paper is the heat transfer characteristic with the oscillatory velocity being close to the flow velocity in the velocity boundary layer under nonoscillation condition. The results show that a sevenfold increase in space-time averaged Nusselt number is achieved. Three mechanisms that are responsible for the heat transfer enhancement are identified. In addition, the effects of the governing parameters on the heat transfer are studied over a wide range. The heat transfer enhancement is found to be increased with dimensionless oscillation frequency and amplitude, but decreased with the Grashof number. Another interest of this paper is to optimize the geometry of baffle plates and an optimal baffle height-spacing ratio 0.25–0.50 is found for higher heat transfer rate.
Study on the imaginary temperature of open boundary wall in cylindrical medium by partition allocation method
Authors: Qi H. , Ruan L. M. , Liu L. H.
Published: July 2005

By the partition allocation method, the radiative heat transfer in a cylindrical medium is approximated, in which every subdomain is overlapped with each other and isolated by an imaginary black wall at certain temperatures. The flux equivalent temperature (FET) from the incident radiative flux on the imaginary interface is proposed as the imaginary temperature of open boundary. Compared with the conventional method of the local medium temperature (LMT) as the imaginary temperature, the FET method is more suitable. The effects of the overlap optical thickness and the aspect ratio on the accuracy of partition allocation method were also investigated.
Fluid Flow and Thermal Characteristics of a Microchannel Heat Sink Subject to an Impinging Air Jet
Authors: Jang Seok Pil , Kim Sung Jin
Published: July 2005

In the present study, fluid-flow and heat-transfer characteristics of a microchannel heat sink subject to an impinging jet are experimentally investigated. In order to evaluate the cooling performance of a microchannel heat sink subject to an impinging jet under the condition of fixed pumping power, the pressure drop across the heat sink and temperature distributions at its base are measured. Specifically, a microthermal sensor array is fabricated and used to accurately measure temperature distributions at the base of the heat sink. Based on these experimental results, a correlation for the pressure drop across a microchannel heat sink subject to an impinging jet and a correlation for its thermal resistance are suggested. In addition, it is shown that the cooling performance of an optimized microchannel heat sink subject to an impinging jet is enhanced by about 21% compared to that of the optimized microchannel heat sink with a parallel flow under the fixed-pumping-power condition.
Heat Transfer Studies in the Flow Over Shallow Cavities
Authors: Zdanski Paulo S. B. , Ortega M. A. , Fico Nide G. C. R.
Published: July 2005

Fluid flows along a shallow cavity. A numerical study was conducted to investigate the effects of heating the floor of the cavity. In order to draw a broader perspective, a parametric analysis was carried out, and the influences of the following parameters were investigated: (i) cavity aspect ratio, (ii) turbulence level of the oncoming flow, and (iii) Reynolds number. A finite-difference computer code was used to integrate the incompressible Reynolds-averaged Navier–Stokes equations. The code, recently developed by the authors, is of the pressure-based type, the grid is collocated, and artificial smoothing terms are added to control eventual odd–even decoupling and nonlinear instabilities. The parametric study revealed and helped to clarify many important physical aspects. Among them, the so called “vortexes encapsulation,” a desirable effect, because the capsule works well as a kind of fluidic thermal insulator. Another important point is related to the role played by the turbulent diffusion in the heat transfer mechanism.
On the Three-Dimensional Structure of Turbulent Spots
Authors: Chong T. P. , Zhong S.
Published: July 2005

A detailed measurement of turbulent spots propagating in a laminar boundary layer over a flat plate was made at a zero pressure gradient and three favorable pressure gradients. Data were recorded across the span of turbulent spots at a number of streamwise locations along the plate using a hot-wire probe and surface-mounted hot films. In this work we aim at extending the existing studies that are largely based upon measurements made in the plane of symmetry of the spots and away from the wall and investigating the three-dimensional structure of turbulent spots and its dependence on streamwise pressure gradients. The results from the present experiment reveal some interesting aspects of the overall structure of the spots and the role that regions with negative velocity perturbations play in the spanwise growth of turbulent spots. The presence of a spanwise overhang is also confirmed that is believed to be responsible for the smaller spreading angle of spots measured at the wall. This finding is expected to have important implications to the development of improved transition models that are used to predict heat transfer and skin friction for turbine blades.
Calculation of the Mixed-Out State in Turbomachine Flows
Authors: Prasad Anil
Published: July 2005

A systematic and rational methodology for the calculation of an equilibrium state from an initial nonuniform flow field, is presented with particular emphasis on the underlying assumptions and their attendant justifications. The imposed conservation criteria that are used to define a final state from the initial one depend on the coordinate system and flow configuration being analyzed. The imposition of these criteria for flow in parallel-walled annular ducts defines a state of complete (mechanical and thermal) equilibrium, for which radial profiles of the velocity components, static pressure and temperature assume a specific form for a perfect gas. A robust method for solving the system of equations that define the state of complete equilibrium (or mixed-out state) is presented using an efficient algorithm. The procedure is applied to the swirling flow exiting an isolated transonic compressor, and comparisons are made with other available methods of averaging flow fields.
IS THE NAKED SINGULARITY INCOMPATIBLE TO QUANTUM GRAVITY?
Authors: XIANG LI , SHEN YOU-GEN
Published: July 2005

In this paper two consequences of the generalized uncertainty principle (GUP) are discussed in a heuristic manner. Both could be regarded as the evidences that prefer the cosmic censorship hypothesis (CCH). The first one is that the second law tends to decline the massless charged particles if the effects of the GUP on the thermodynamics of a de Sitter spacetime are considered. This weakens the threat to the horizon of an extreme charged black hole. The second one is that the uv/ir correspondence provides a constraint on the relation between the energy and the size of a system, which is incompatible to the naked singularities.
Regulation of energy liberation during steady sarcomere shortening
Authors: Tchaicheeyan Oren , Landesberg Amir
Published: July 2005

Energy liberation rate ( Ė) during steady muscle shortening is a monotonic increasing or biphasic function of the shortening velocity ( V). The study examines three plausible hypotheses for explaining the biphasic Ė-V relationship (EVR): 1) the cross-bridge (XB) turnover rate from non-force-generating (weak) to force-generating (strong) conformation decreases as V increases; 2) XB kinetics is determined by the number of strong XBs (XB -XB cooperativity); and 3) the affinity of troponin for calcium is modulated by the number of strong XBs (XB -Ca cooperativity). The relative role of the various energy-regulating mechanisms is not well defined. The hypotheses were tested by coupling calcium kinetics with XB cycling. All three hypotheses yield identical steady-state characteristics: 1) hyperbolic force-velocity relationship; 2) quasi-linear stiffness-force relationship; and 3) biphasic EVR, where Ė declines at high V due to decrease in the number of cycling XBs or in the weak-to-strong transition rate. The hypotheses differ in the ability to describe the existence of both monotonic and biphasic EVRs and in the effect of intracellular free calcium concentration ([Ca2+]i) on the EVR peak. Monotonic and biphasic EVRs with a shift in EVR peak to higher velocity at higher [Ca2+]iare obtained only by XB -Ca cooperativity. XB -XB cooperativity provides only biphasic EVRs. A direct effect of V on XB kinetics predicts that EVR peak is obtained at the same velocity independently of [Ca2+]i. The study predicts that measuring the dependence of the EVR on [Ca2+]iallows us to test the hypotheses and to identify the dominant energy-regulating mechanism. The established XB -XB and XB -Ca mechanisms provide alternative explanations to the various reported EVRs.