bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and functional complexity of the humoral response against theTrypanosoma cruziribosomal P2βprotein in patients with chronic Chagas’ heart disease
Authors: MAHLER E , HOEBEKE J , LEVIN M J 
Published: May 2004

SUMMARYHigh levels of antibodies against the C-terminus of the Trypanosoma cruzi TcP2β ribosomal protein, defined by the peptide EEEDDDMGFGLFD, named R13, have been measured in sera from patients with chronic Chagas’ Heart Disease (cChHD). These antibodies also recognize an epitope on the second extracellular loop of the β1-adrenergic receptor, inducing a functional response on cardiomyocytes. The aim of this study was to gain novel insights into the structural basis of this cross-reactivity as well as to evaluate the origin of anti-M2- cholinergic receptor antibodies, which are also commonly found in cChHD patients. To address these questions we immunopurified anti-R13 antibodies and studied the structural requirements of epitope recognition. Results showed that the immunopurified antibodies recognized a conformation of R13 in which the third Glu residue was essential for binding, explaining their low affinity for the mammalian homologue (peptide H13: EESDDDMGFGLFD). Alanine mutation scanning showed individual variations in epitope recognition in each of the studied patients. The importance of a negatively charged residue at position 3 for the recognition of anti-R13 antibodies was further confirmed by competition experiments using a Ser3-phosphorylated H13 analogue, which had 10 times more affinity for the anti-R13 antibody than the native H13 peptide. Moreover, anti-R13 antibodies stimulated either the β1-adrenergic or the M2-cholinergic receptor, in strict agreement with the functional properties of the IgG fractions from which they derived, demonstrating that the same parasite antigen may generate antibody specificities with different functional properties. This may be a clue to explain the high variability of electrophysiological disturbances found in cChHD.
Apoptosis as a mechanism for cell surface expression of the autoantigen pyruvate dehydrogenase complex
Authors: MACDONALD P , PALMER J , KIRBY J A , JONES D E J 
Published: May 2004

SUMMARY
A number of antigens implicated in the pathogenesis of autoimmune diseases including Sjogren's syndrome and systemic lupus erythematosus (SLE) are expressed aberrantly by apoptotic cells. It is also known that apoptogenic proteins are released from the mitochondrial intermembrane space at an early stage during the induction and development of apoptosis. Combination of this evidence led us to test the hypothesis that apoptotic mechanisms provide an explanation for the abnormal expression of the inner mitochondrial enzyme, pyruvate dehydrogenase complex (PDC), observed on the surface of some cells in patients with the autoimmune liver disease primary biliary cirrhosis (PBC). Using one murine and two human cell lines it was found that the induction of apoptosis led to early detection of PDC within the cytoplasm. However, cytochrome c oxidase subunit 4 (COX 4), which is also present on the inner surface of the inner mitochondrial membrane, remained within the mitochondria. Immunoreactive PDC was also detected on the outer surface of the intact plasma membrane of cells sampled after the induction of apoptosis. Serial release of PDC to the cytoplasm and then onto the external surface of the plasma membrane provides direct evidence that the antigen on the cell surface is of mitochondrial origin. Immunoreactivity specific for PDC is strongly implicated in the pathogenesis of PBC, but this autoantigen is normally concealed from the immune system by three membrane systems. Release of PDC onto the cell surface during apoptosis provides a possible route for recognition of this antigen by the immune system which could contribute to both afferent and efferent phases of the disease process.
Autoimmunity and glomerulonephritis in mice with targeted deletion of the serum amyloid P component gene: SAP deficiency or strain combination?
Authors: Gillmore Julian D. , Hutchinson Winston L. , Herbert Jeff. , Bybee Alison , Mitchell Daniel A. , Hasserjian Robert P. , Yamamura Ken‐Ichi , Suzuki Misao , Sabin Caroline A. , Pepys Mark B. 
Published: May 2004

SummaryHuman serum amyloid P component (SAP) binds avidly to DNA, chromatin and apoptotic cells in vitro and in vivo. 129\Sv × C57BL\6 mice with targeted deletion of the SAP gene spontaneously develop antinuclear autoantibodies and immune complex glomerulonephritis. SAP‐deficient animals, created by backcrossing the 129\Sv SAP gene deletion into pure line C57BL\6 mice and studied here for the first time, also spontaneously developed broad spectrum antinuclear autoimmunity and proliferative immune complex glomerulonephritis but without proteinuria, renal failure, or increased morbidity or mortality. Mice hemizygous for the SAP gene deletion had an intermediate autoimmune phenotype. Injected apoptotic cells and isolated chromatin were more immunogenic in SAP–\– mice than in wild‐type mice. In contrast, SAP‐deficient pure line 129\Sv mice did not produce significant autoantibodies either spontaneously or when immunized with extrinsic chromatin or apoptotic cells, indicating that loss of tolerance is markedly strain dependent. However, SAP deficiency in C57BL\6 mice only marginally affected plasma clearance of exogenous chromatin and had no effect on distribution of exogenous nucleosomes between the liver and kidneys, which were the only tissue sites of catabolism. Furthermore, transgenic expression of human SAP in the C57BL\6 SAP knockout mice did not abrogate the autoimmune phenotype. This may reflect the different binding affinities of mouse and human SAP for nuclear autoantigens and\or the heterologous nature of transgenic human SAP in the mouse. Alternatively, the autoimmunity may be independent of SAP deficiency and caused by expression of 129\Sv chromosome 1 genes in the C57BL\6 background.
Induction of immune responses against human papillomaviruses by hypervariable epitope constructs
Authors: Reddy K. Jyotsna , Banapour Babak , Anderson David E. , Lee Sang H. , Marquez Juan P. , Carlos Maria P. , Torres Jose V. 
Published: May 2004

SummaryAn ideal prophylactic vaccine against human papillomaviruses (HPV) would be one that can induce broadly reactive antibody titres to at least the major oncogenic strains of HPV. It has been previously shown that HPV structural proteins are highly immunogenic but fail to elicit cross‐reactive immune responses against heterologous strains of HPV. Recent studies have demonstrated that the immunity induced by virus‐like particles is mostly type specific. In the present study, we determined the breadth of reactivity of antibodies induced in mice immunized with hypervariable epitope constructs (HECs), which represent sequence variants of immunodominant B‐cell epitopes of the major capsid protein L1 of HPV. In order to test the breadth of reactivity, sera from immunized mice were tested against peptides representing analogous sequences of HPV types 16, 18, 31 and 45. Mice immunized with HECs based on two epitopes mounted antibody responses that cross‐reacted with two different analogues, 16 and 18. Significantly, antibodies from mice immunized with HECs also inhibited haemagglutination mediated by HPV‐16 L1 VLPs, suggesting that immunization resulted in the development of antibodies that could bind to viral capsid proteins in their native conformation. Our observations suggest that HECs may overcome the restriction of type specific immunity against HPV.
Differential effect of immune cells on non‐pathogenic Gram‐negative bacteria‐induced nuclear factor‐κB activation and pro‐inflammatory gene expression in intestinal epithelial cells
Authors: Haller D. , Holt L. , Parlesak A. , Zanga J. , Bäuerlein A. , Sartor R. B. , Jobin C. 
Published: May 2004

SummaryWe have previously shown that non‐pathogenic Gram negative bacteria induce RelA phosphorylation, nuclear factor (NF)‐κB transcriptional activity and pro‐inflammatory gene expression in intestinal epithelial cells (IEC) in vivo and in vitro. In this study, we investigated the molecular mechanism of immune‐epithelial cell cross‐talk on Gram‐negative enteric bacteria‐induced NF‐κB signalling and pro‐inflammatory gene expression in IEC using HT‐29/MTX as well as CaCO‐2 transwell cultures Interestingly, while differentiated HT‐29/MTX cells are unresponsive to non‐pathogenic Gram negative bacterial stimulation, interleukin‐8 (IL‐8) mRNA accumulation is strongly induced in Escherichia coli‐ but not Bacteroides vulgatus‐stimulated IEC cocultured with peripheral blood (PBMC) and lamina propria mononuclear cells (LPMC). The presence of PBMC triggered both E. coli‐ and B. vulgatus‐induced mRNA expression of the Toll‐like receptor‐4 accessory protein MD‐2 as well as endogenous IκBα phosphorylation, demonstrating similar capabilities of these bacteria to induce proximal NF‐κB signalling. However, B. vulgatus failed to trigger IκBα degradation and NF‐κB transcriptional activity in the presence of PBMC. Interestingly, B. vulgatus‐ and E. coli‐derived lipopolysaccharide‐induced similar IL‐8 mRNA expression in epithelial cells after basolateral stimulation of HT‐29/PBMC cocultures. Although luminal enteric bacteria have adjuvant and antigenic properties in chronic intestinal inflammation, PBMC from patients with active ulcerative colitis and Crohn's disease differentially trigger epithelial cell activation in response to E. coli and E. coli‐derived LPS. In conclusion, this study provides evidence for a differential regulation of non‐pathogenic Gram‐negative bacteria‐induced NF‐κB signalling and IL‐8 gene expression in IEC cocultured with immune cells and suggests the presence of mechanisms that assure hyporesponsiveness of the intestinal epithelium to certain commensally enteric bacteria.
Modulation of immune responses to bovine herpesvirus‐1 in cattle by immunization with a DNA vaccine encoding glycoprotein D as a fusion protein with bovine CD154
Authors: Manoj Sharmila , Griebel Philip J. , Babiuk Lorne A. , Van Drunen Littel‐Van Den Hurk Sylvia 
Published: May 2004

SummaryThe objective of this study was to determine whether a DNA vaccine encoding bovine CD154 linked to a truncated version of bovine herpesvirus‐1 (BHV‐1) glycoprotein D (tgD‐CD154) induces enhanced tgD‐specific immune responses in cattle. In vitro characterization demonstrated that tgD and tgD‐CD154 both bind to cultured bovine B cells, whereas only tgD‐CD154 induces interleukin‐4‐dependent proliferation, suggesting that tgD‐CD154 specifically binds the CD40 receptor and induces receptor signalling. Calves were immunized with plasmid encoding either tgD or tgD‐CD154 by intradermal injection with a needle‐free device. After two immunizations, tgD‐specific immune responses were observed in both vaccinated groups and after challenge with BHV‐1 these responses further increased. Animals immunized with plasmid encoding tgD‐CD154 had significantly higher tgD‐specific serum titres of immunoglobulins G and A but significantly lower numbers of tgD‐specific interferon‐γ‐secreting cells than animals immunized with plasmid encoding tgD after BHV‐1 challenge. This suggests that the expression of an antigen as a chimeric protein with CD154 can qualitatively alter immune responses in cattle. Since we previously showed that plasmid encoding tgD‐CD154 induces significantly enhanced secondary tgD‐specific antibody responses in sheep, there appear to be interspecies differences in the immune responses induced by tgD‐CD154, which suggests that both proteins in the chimeric molecule may influence protein targeting and the induction of an immune response.
Ezrin/radixin/moesin proteins and Rho GTPase signalling in leucocytes
Authors: Ivetic Aleksandar , Ridley Anne J. 
Published: May 2004

SummaryThe ezrin/radixin/moesin (ERM) family of actin‐binding proteins act both as linkers between the actin cytoskeleton and plasma membrane proteins and as signal transducers in responses involving cytoskeletal remodelling. The Rho family of GTPases also regulate cytoskeletal organisation, and several molecular pathways linking ERM proteins and Rho GTPases have been described. This review discusses recent findings on ERM protein function in leucocytes and how these may be integrated with Rho GTPase signalling.
The expanding clinical spectrum of Anderson–Fabry disease: a challenge to diagnosis in the novel era of enzyme replacement therapy
Authors: Hauser A. C. , Lorenz M. , Sunder‐Plassmann G. 
Published: May 2004

Abstract.Anderson–Fabry disease is an X‐linked recessive lysosomal storage disease resulting from deficient α‐galactosidase A activity. The conception of the disease has changed within the last decade. Studies of the last years have shown that the disease is not limited to the classical full‐blown manifestation in affected males, which is well known since more than a century, but may also occur in carrier females. The phenomenology may differ in severity and kind of organ manifestation. Cardiac and renal variants with solely disease manifestation of these organs have also been described in an increasing number. It is likely that a spectrum exists regarding α‐galactosidase A activity in both genders on the one hand, and an additional one regarding the severity and the number of organs affected on the other. The purpose of this review is to sharpen physicians’ perception of this disease. Early and accurate diagnosis is mandatory considering that this disorder is now, after introduction of the novel enzyme replacement therapy, a treatable disease.
Coronary heart disease in a patient with cerebrotendinous xanthomatosis
Authors: Valdivielso P. , Calandra S. , Durán J. C. , Garuti R. , Herrera E. , González P. 
Published: May 2004

Abstract.Coronary heart disease is a prevalent condition and a leading cause of death in developed countries. Most cases are due to the cluster of classical risk factors, such as smoking, diabetes, high blood pressure and dyslipidaemia. However, a few patients develop severe and premature arteriosclerosis in spite of absence of common risk factors. Here, we present the clinical, analytical and molecular features of a 36‐years‐old man who died from advanced ischaemic heart disease as a result of cerebrotendinous xanthomatosis (CTX), a rare condition characterized by elevation in plasma and most tissues of cholestanol and where neurological impairment is the hallmark of this disease. We discuss the relevance of heart disease and the mechanism leading to accelerate arteriosclerosis is CTX.
Allergen avoidance does not alter airborne cat allergen levels in classrooms
Authors: Karlsson A.‐S. , Renström A. , Hedrén M. , Larsson K. 
Published: May 2004

Background:  Some schools in Sweden offer allergen avoidance classrooms for allergic children with severe asthma. However, the measures commonly used to achieve a reduction in allergen levels have not been properly evaluated. The aim of the present prospective study was to study whether the levels of airborne cat allergen are altered after introducing feasible intervention measures in classrooms, without interfering with peoples’ freedom of choice regarding pet ownership.Methods:  Twenty‐five classes, including five established allergy prevention classrooms participated in the study during a school year. After one term, six classes underwent a number of intervention measures recommended by the Swedish National Institute of Public Health. Curtains, upholstery and plants were removed, bookshelves were replaced with cupboards and regular cleaning was increased. Airborne dust was collected weekly (32 weeks) using duplicate Petri dishes (n = 1574) and on six occasions using two personal air samplers in each class (n = 264).Results:  Airborne cat allergen levels were showing a similar variability throughout the whole study in all classes. Despite extensive measures in order to reduce allergen exposure, cat allergen levels were unaltered in the six classes after intervention. Allergen levels were not significantly lower in the established allergy prevention classes, compared with the other classes. Cat allergen levels differed, however, significantly between classes with few and many cat owners (P < 0.05).Conclusions:  We conclude that the recommended allergen avoidance measures used in this study did not reduce airborne cat allergen. It seems plausible that measures that fail to reduce allergen levels also fail to influence health status in allergic children but this remains to be shown.
Quality and Distribution of Assimilates within the Whole Plant of Lupines (L. albus and L. mutabilis) Influenced by Water Stress
Authors: Carvalho I. S. , Ricardo C. P. , Chaves M. 
Published: May 2004

AbstractLupine crops (Lupinus albus and L. mutabilis) often experience water deficits during grain filling, thereby altering partitioning of assimilates. Water deficit, imposed at the beginning of seed production (15 days after anthesis, daa), brought about differences in assimilate partitioning and chemical composition within the whole plant. In both species, water stress (ws) was responsible for a significant decrease in plant water status and gas exchange. In spite of little effect on total biomass, leaf area was reduced for approximately half of the control treatment. The main effects of ws on chemical composition of different organs were a decrease in total oil and an increase in total soluble sugar content in leaves; an increase in both oil and soluble sugars in stems; and a decrease in total oil and total soluble sugar content in seeds. The data suggest that under ws conditions, imposed at flowering, lupine assimilates are stored in stems and pods and later retranslocated to the developing seeds.
Species richness of benthic macrofauna in Danish estuaries and coastal areas
Authors: Josefson A. B. , Hansen J. L. S. 
Published: May 2004

ABSTRACTAim  Cross‐system comparisons of species richness of benthic macrofauna and environmental factors were made of estuaries and adjacent sea areas in order to reveal possible regulating factors of estuarine biodiversity.Location  Denmark.Methods  Annual species abundance and biomass data from four years, from unvegetated soft sea/estuary floors were used from 26 grids, of which 15 were situated in estuaries. Bottom water data for oxygen concentration, salinity, and temperature were obtained from stations in or close to, the grids. Data on nutrient loading, water residence time and morphology were obtained for whole estuaries. Species richness from the grids, standardized to the same sample size, were related to environmental variables using linear regression.Results  Species richness was unrelated to oxygen deficiency and productivity, but positively related to salinity. However, an equally high degree of explanation (R2 ∼ 0.70) was obtained using a model where richness was positively related to saltwater flux, which was computed from estuary volume and residence time and corrected for freshwater flux. The relationship was present for the dominating groups with pelagic dispersal, Annelida and Mollusca, but not for Crustacea, where recruitment is mainly by benthic pathways. Saltwater flux was strongly positively correlated with salinity, illustrating the high importance of flux from adjacent sea areas for water renewal in Danish estuaries. Similarity of species composition was greater for sites within than between saltwater current pathways, and the increases of richness with saltwater flux and salinity in the estuaries was largely due to marine species occurring in the open sea areas.Conclusion  Danish estuaries are largely open systems where a part of estuarine species richness is sustained by dispersal from a species pool in adjacent seas. Results are consistent with the barrier prediction of island biogeography theory, but not the island size prediction.
Hypoxia induces adenosine release from the rat carotid body
Authors: Conde Sílvia V. , Monteiro Emília C. 
Published: May 2004

AbstractThe effect of hypoxia on the release of adenosine was studied in vitro in the rat whole carotid body (CB) and compared with the effect of hypoxia (2%, 5% and 10% O2) on adenosine concentrations in superior cervical ganglia (SCG) and carotid arteries. Moderate hypoxia (10% O2) increased adenosine concentrations released from the CBs by 44%, but was not a strong enough stimulus to evoke adenosine release from SCG and arterial tissue. The extracellular pathways of adenosine production in rat CBs in normoxia and hypoxia were also investigated. S‐(p‐nitrobenzyl)‐6‐thioinosine (NBTI) and dipyridamole were used as pharmacological tools to inhibit adenosine equilibrative transporters (ENT) and α,β‐methylene ADP (AOPCP) to inhibit ecto‐5′‐nucleotidase. Approximately 40% of extracellular adenosine in the CB came from the extracellular catabolism of ATP, under both normoxic and hypoxic conditions. Low pO2 triggers adenosine efflux through activation of NBTI‐sensitive ENT. This effect was only apparent in hypoxia and when adenosine extracellular concentrations were reduced by the blockade of ecto‐5′‐nucleotidase. We concluded that CB chemoreceptor sensitivity could be related to its low threshold for the release of adenosine in response to hypoxia here quantified for the first time.
Regulation and function of somatostatin receptors
Authors: Olias Gisela , Viollet Cécile , Kusserow Heike , Epelbaum Jacques , Meyerhof Wolfgang 
Published: May 2004

AbstractThis review summarizes the latest advances that have been made to elucidate the somatostatinergic system in respect to somatostatin receptor evolution, the development of receptor agonists/antagonists, receptor regulation, signal transduction, effects on cell proliferation, receptor–receptor or receptor–protein interactions and receptor function.
Regulation of protein kinase C by the anti‐Parkinson drug, MAO‐B inhibitor, rasagiline and its derivatives, in vivo
Authors: Bar‐Am Orit , Yogev‐Falach Merav , Amit Tamar , Sagi Yotam , Youdim Moussa B. H. 
Published: May 2004

AbstractWe have recently shown that the anti‐Parkinson‐propargyl‐containing monoamine oxidase B (MAO‐B) inhibitor drug, rasagiline [N‐propargyl‐(1R)‐aminoindan], and its cholinesterase inhibitor derivatives TV3326 and TV3279, regulate amyloid precursor protein (APP) processing by a protein kinase C (PKC)‐dependent mechanism in SH‐SY5Y neuroblastoma and PC12 cells. In the present study, we investigated the effect of rasagiline and its derivatives on the regulation of the PKC‐dependent mechanism and APP processing under in vivo conditions. Administration of rasagiline (0.1 mg/kg) to male C57/BL mice for 14 days significantly decreased membrane‐bound holoprotein APP levels in the hippocampus. Additionally, we observed that rasagiline up‐regulated p‐PKC levels and the expression of α and ε PKC isozymes in the hippocampus, indicating that the mechanism by which rasagiline affects APP processing may be related to PKC‐associated signalling. The results also demonstrate that rasagiline treatment significantly elevated the levels of phosphorylated myristoylated alanine‐rich C kinase substrate (p‐MARCKS), a major substrate for PKC, as well as the levels of receptors for activated C kinase 1 (RACK1). Similar effects on APP and PKC levels were also demonstrated for the two cholinesterase inhibitor derivatives of rasagiline, TV3326 and TV3279. These results indicate that rasagiline and its derivatives regulate PKC‐dependent mechanisms and APP processing. The activation and induction of PKC and MARCKS by these drugs may have a crucial role not only in their neuroprotective activity, but also in their ability to affect neuronal plasticity and spatial learning processes.