bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human colorectal tumors and metastases express Gb3 and can be targeted by an intestinal pathogen-based delivery tool
Authors: Falguières Thomas , Maak Matthias , von Weyhern Claus , Sarr Marianne , Sastre Xavier , Poupon Marie-France , Robine Sylvie , Johannes Ludger , Janssen Klaus-Peter 
Published: August 2008

Abstract
The targeting of solid tumors requires delivery tools that resist intracellular and extracellular inactivation, and that are taken up specifically by tumor cells. We have shown previously that the recombinant nontoxic B-subunit of Shiga toxin (STxB) can serve as a delivery tool to target digestive tumors in animal models. The aim of this study was to expand these experiments to human colorectal cancer. Tissue samples of normal colon, benign adenomas, colorectal carcinomas, and liver metastases from 111 patients were obtained for the quantification of the expression of the cellular STxB receptor, the glycosphingolipid globotriaosyl ceramide (Gb3 or CD77). We found that compared with normal tissue, the expression of Gb3 was strongly increased in colorectal adenocarcinomas and their metastases, but not in benign adenomas. Short-term primary cultures were prepared from samples of 43 patients, and STxB uptake was studied by immunofluorescence microscopy. Of a given tumor sample, on average, 80% of the cells could visibly bind STxB, and upon incubation at 37°C, STxB was transported to the Golgi apparatus, following the retrograde route. This STxB-specific intracellular targeting allows the molecule to avoid recycling and degradation, and STxB could consequently be detected on tumor cells even 5 days after initial uptake. In conclusion, the targeting properties of STxB could be diverted for the delivery of contrast agents to human colorectal tumors and their metastases, whose early detection and specific targeting remains one of the principal challenges in oncology. [Mol Cancer Ther 2008;7(8):2498–508]
The majority of cutaneous marginal zone B-cell lymphomas expresses class-switched immunoglobulins and develops in a T-helper type 2 inflammatory environment
Authors: van Maldegem Febe , van Dijk Remco , Wormhoudt Thera A. M. , Kluin Philip M. , Willemze Rein , Cerroni Lorenzo , van Noesel Carel J. M. , Bende Richard J. 
Published: August 2008

AbstractExtranodal marginal zone B-cell lymphomas (MZBCLs) arise on a background of chronic inflammation resulting from organ-specific autoimmunity, infection, or by unknown causes. Well-known examples are salivary gland MZBCL in Sjögren's sialadenitis and gastric MZBCL in Helicobacter pylori gastritis. MZBCLs express CXCR3, a receptor for interferon-γ–induced chemokines highly expressed in the chronic inflammatory environment. The immunoglobulin (Ig) variable heavy/light chain (IgVH/IgVL) gene repertoire of salivary gland and gastric MZBCL appears restricted and frequently encodes B-cell receptors with rheumatoid factor reactivity. Primary cutaneous marginal zone B-cell lymphomas (PCMZLs) are regarded as the skin-involving counterparts of extranodal MZBCLs. Although PCMZLs have been associated with Borrelia burgdorferi dermatitis, PCMZLs generally arise because of unknown causes. We studied an extensive panel of PCMZLs and show that PCMZLs do not conform to the general profile of extranodal MZBCL. Whereas most noncutaneous MZBCLs express IgM, PCMZLs in majority express IgG, IgA, and IgE and do not show an obvious immunoglobulin repertoire bias. Furthermore, the isotype-switched PCMZLs lack CXCR3 and seem to arise in a different inflammatory environment, compared with other extranodal MZBCLs.
Bovine CD14 gene characterization and relationship between polymorphisms and surface expression on monocytes and polymorphonuclear neutrophils
Authors: Ibeagha-Awemu Eveline M , Lee Jai-Wei , Ibeagha Aloysius E , Zhao Xin 
Published: August 2008

AbstractBackgroundCD14 is an important player in host innate immunity in that it confers lipopolysaccharide sensitivity to cell types like neutrophils, monocytes and macrophages. The study was aimed at characterizing the CD14 gene of cattle for sequence variations and to determine the effect of variations on the expression of the protein on the surfaces of monocytes and neutrophils in healthy dairy cows.ResultsFive SNPs were identified: two within the coding regions (g.A1908G and g.A2318G, numbering is according to GenBank No. EU148609), one in the 5' (g.C1291T) and two in the 3' (g.A2601G and g.G2621T) untranslated regions. SNP 1908 changes amino acid 175 of the protein (p.Asn175Asp, numbering is according to GenBank No. ABV68569), while SNP 2318 involves a synonymous codon change. Coding region SNPs characterized three gene allelesA(GenBank No. EU148609),A1(GenBank No. EU148610) andB(GenBank No. EU148611) and two deduced protein variants A (ABV68569 and ABV68570) and B (ABV68571). Protein variant A is more common in the breeds analyzed. All SNPs gave rise to 3 haplotypes for the breeds. SNP genotype 1908AG was significantly (P < 0.01) associated with a higher percentage of neutrophils expressing more CD14 molecules on their surfaces. The promoter region contains several transcription factor binding sites, including multiple AP-1 and SP1 sites and there is a high conservation of amino acid residues between the proteins of closely related species.ConclusionThe study has provided information on sequence variations within the CD14 gene and proteins of cattle. The SNP responsible for an amino acid exchange may play an important role in the expression of CD14 on the surfaces of neutrophils. Further observations involving a larger sample size are required to validate our findings. Our SNP and association analyses have provided baseline information that may be used at defining the role of CD14 in mediating bacterial infections. The computational analysis on the promoter and comparative analysis with other species has revealed regions of regulatory element motifs that may indicate important regulatory effects on the gene.
Regression toward the mean – a detection method for unknown population mean based on Mee and Chua's algorithm
Authors: Ostermann Thomas , Willich Stefan N , Lüdtke Rainer 
Published: August 2008

Abstract

Background
Regression to the mean (RTM) occurs in situations of repeated measurements when extreme values are followed by measurements in the same subjects that are closer to the mean of the basic population. In uncontrolled studies such changes are likely to be interpreted as a real treatment effect.

Methods
Several statistical approaches have been developed to analyse such situations, including the algorithm of Mee and Chua which assumes a known population mean μ. We extend this approach to a situation where μ is unknown and suggest to vary it systematically over a range of reasonable values. Using differential calculus we provide formulas to estimate the range of μ where treatment effects are likely to occur when RTM is present.

Results
We successfully applied our method to three real world examples denoting situations when (a) no treatment effect can be confirmed regardless which μ is true, (b) when a treatment effect must be assumed independent from the true μ and (c) in the appraisal of results of uncontrolled studies.

Conclusion
Our method can be used to separate the wheat from the chaff in situations, when one has to interpret the results of uncontrolled studies. In meta-analysis, health-technology reports or systematic reviews this approach may be helpful to clarify the evidence given from uncontrolled observational studies.
The efficiency and effectiveness of utilizing diagrams in interviews: an assessment of participatory diagramming and graphic elicitation
Authors: Umoquit Muriah J , Dobrow Mark J , Lemieux-Charles Louise , Ritvo Paul G , Urbach David R , Wodchis Walter P 
Published: August 2008

Abstract

Background
This paper focuses on measuring the efficiency and effectiveness of two diagramming methods employed in key informant interviews with clinicians and health care administrators. The two methods are 'participatory diagramming', where the respondent creates a diagram that assists in their communication of answers, and 'graphic elicitation', where a researcher-prepared diagram is used to stimulate data collection.

Methods
These two diagramming methods were applied in key informant interviews and their value in efficiently and effectively gathering data was assessed based on quantitative measures and qualitative observations.

Results
Assessment of the two diagramming methods suggests that participatory diagramming is an efficient method for collecting data in graphic form, but may not generate the depth of verbal response that many qualitative researchers seek. In contrast, graphic elicitation was more intuitive, better understood and preferred by most respondents, and often provided more contemplative verbal responses, however this was achieved at the expense of more interview time.

Conclusion
Diagramming methods are important for eliciting interview data that are often difficult to obtain through traditional verbal exchanges. Subject to the methodological limitations of the study, our findings suggest that while participatory diagramming and graphic elicitation have specific strengths and weaknesses, their combined use can provide complementary information that would not likely occur with the application of only one diagramming method. The methodological insights gained by examining the efficiency and effectiveness of these diagramming methods in our study should be helpful to other researchers considering their incorporation into qualitative research designs.
The leukoaraiosis is more prevalent in the large artery atherosclerosis stroke subtype among Korean patients with ischemic stroke
Authors: Lee Seung-Jae , Kim Joong-Seok , Lee Kwang-Soo , An Jae-Young , Kim Woojun , Kim Yeong-In , Kim Bum-Soo , Jung So-Lyung 
Published: August 2008

Abstract

Background
Several studies have suggested that the specific stroke subtype may influence the presence of leukoaraiosis in patients with ischemic stroke. We investigated the association between stroke subtype and leukoaraiosis in Korean patients with ischemic stroke by MRI.

Methods
There were 594 patients included in this study that were classified as large artery disease, lacune and cardioembolic stroke. For large-artery disease, the analysis focused on the intracranial or extracranial location of the stenosis, and the multiplicity of the stenotic lesions. Leukoaraiosis grading was performed according to the Atherosclerosis Risk in Communities Study.

Results
There was a significant association between leukoaraiosis and the stroke subtypes; the large-artery-disease group had a higher prevalence of leukoaraiosis than did the other groups (55.4% in the large-artery-disease group, 30.3% in the lacunar group and 14.3% in the cardioembolic group, P = 0.016 by chi-square test). On the multivariate linear regression analysis, age, the presence of hypertension, previous stroke and stroke subtype were independently associated with the presence of leukoaraiosis. In the sub analysis of the large-artery-disease group, the leukoaraiosis had a tendency to be more prevalent in the mixed and intracranial stenosis group than did the extracranial stenosis group (45.5% in the mixed group, 40.3% in the intracranial group and 26.9% in the extracranial group, P = 0.08 by chi-square test).

Conclusion
The association of leukoaraiosis with large-artery disease in this study might be due to the relatively high prevalence of intracranial occlusive lesions in Korean stroke patients compared to other ethnic groups.
15-deoxy-delta12,14-prostaglandin J2 attenuates endothelial-monocyte interaction: implication for inflammatory diseases
Authors: Prasad Ratna , Giri Shailendra , Singh Avtar K , Singh Inderjit 
Published: August 2008

AbstractBackgroundThe Infiltration of leukocytes across the brain endothelium is a hallmark of various neuroinflammatory disorders. Under inflammatory conditions, there is increased expression of specific cell adhesion molecules (CAMs) on activated vascular endothelial cells which increases the adhesion and infiltration of leukocytes. TNFα is one of the major proinflammatory cytokines that causes endothelial dysfunction by various mechanisms including activation of transcription factor NF-κB, a key transcription factor that regulates expression of CAMs. Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear hormone superfamily of ligand-activated transcriptional factors. 15-deoxy-δ 12, 14-prostaglandin J2 (15d-PGJ2) is a well recognized natural ligand of PPARγ and possesses anti-inflammatory properties bothin vitroandin vivo. This study aims to elucidate the mechanism of 15-PGJ2 on the adhesion of mononuclear cells to activated endothelial cells.MethodsTo delineate the signaling pathway of 15d-PGJ2 mediated effects, we employed anin vitroadhesion assay model of endothelial-monocyte interaction. Expression of CAMs was examined using flow cytometry and real time PCR techniques. To define the mechanism of 15d-PGJ2, we explored the role of NF-κB by EMSA (ElectrophoreticMobilityShiftAssay) gels, NF-κB reporter and p65-transcriptional activities by transient transfection in the brain-derived endothelial cell line (bEND.3).ResultsUsing anin vitroadhesion assay model, we demonstrate that 15d-PGJ2 inhibits TNFα induced monocyte adhesion to endothelial cells, which is mediated by downregulation of endothelial cell adhesion molecules in a PPARγ independent manner. 15d-PGJ2 modulated the adhesion process by inhibiting the TNFα induced IKK-NF-κB pathway as evident from EMSA, NF-κB reporter and p65 mediated transcriptional activity results in bEND.3 cells.ConclusionThese findings suggest that 15d-PGJ2 inhibits inflammation at multiple steps and thus is a potential therapeutic target for various inflammatory diseases.
Hypercalcemia in a patient with disseminated paracoccidioidomycosis: a case report
Authors: Almeida Rafael Moura , Cezana Loureno , Tsukumo Daniela Miti Lemos , de Carvalho-Filho Marco Antônio , Saad Mário José Abdalla 
Published: August 2008

Abstract

Introduction
Hypercalcemia is well described in various granulomatous disorders, such as sarcoidosis, tuberculosis, berylliosis, leprosy and fungal infections. However, the association of Paracoccidioides brasiliensis and hypercalcemia is rare: to the best of our knowledge, only two cases have previously been reported, and neither had a clear documentation of the etiology of the hypercalcemia.

Case presentation
We report the case of a 22-year-old man in whom disseminated infection with paracoccidioidomycosis was associated with hypercalcemia. The patient had a high normal serum level of 1,25-dihydroxyvitamin D and a suppressed parathyroid hormone value, an indication that the hypercalcemia was not mediated by parathyroid hormone and might be associated with 1,25-dihydroxyvitamin D.

Conclusion
The episode resolved readily with administration of corticosteroids, an outcome suggesting that this is an effective treatment of hypercalcemia of this origin. On follow-up, while receiving antifungal therapy for P. brasiliensis the patient's calcium values remained normal.
Sortilin Is a Putative Postendocytic Receptor of Thyroglobulin
Authors: Botta Roberta , Lisi Simonetta , Pinchera Aldo , Giorgi Franco , Marcocci Claudio , Taddei Anna Rita , Fausto Anna Maria , Bernardini Nunzia , Ippolito Chiara , Mattii Letizia , Persani Luca , de Filippis Tiziana , Calebiro Davide , Madsen Peder , Petersen Claus Munck , Marinò Michele 
Published: August 2008

The Vps10p family member sortilin is involved in various cell processes, including protein trafficking. Here we found that sortilin is expressed in thyroid epithelial cells (thyrocytes) in a TSH-dependent manner, that the hormone precursor thyroglobulin (Tg) is a high-affinity sortilin ligand, and that binding to sortilin occurs after Tg endocytosis, resulting in Tg recycling. Sortilin was found to be expressed intracellularly in thyrocytes, as observed in mouse, human, and rat thyroid as well as in FRTL-5 cells. Sortilin expression was demonstrated to be TSH dependent, both in FRTL-5 cells and in mice treated with methimazole and perchlorate. Plasmon resonance binding assays showed that Tg binds to sortilin in a concentration-dependent manner and with high affinity, with Kd values that paralleled the hormone content of Tg. In addition, we found that Tg and sortilin interact in vivo and in cultured cells, as observed by immunoprecipitation, in mouse thyroid extracts and in COS-7 cells transiently cotransfected with sortilin and Tg. After incubation of FRTL-5 cells with exogenous, labeled Tg, sortilin and Tg interacted intracellularly, presumably within the endocytic pathway, as observed by immunofluorescence and immunoelectron microscopy, the latter technique showing some degree of Tg recycling. This was confirmed in FRTL-5 cells in which Tg recycling was reduced by silencing of the sortilin gene and in CHO cells transfected with sortilin in which recycling was increased. Our findings provide a novel pathway of Tg trafficking and a novel function of sortilin in the thyroid gland, the functional impact of which remains to be established.Evidence for a novel pathway of thyroglobulin trafficking and for a possible novel function of sortilin in the thyroid gland is discussed.
Deletion of Dicer in Somatic Cells of the Female Reproductive Tract Causes Sterility
Authors: Nagaraja Ankur K. , Andreu-Vieyra Claudia , Franco Heather L. , Ma Lang , Chen Ruihong , Han Derek Y. , Zhu Huifeng , Agno Julio E. , Gunaratne Preethi H. , DeMayo Francesco J. , Matzuk Martin M. 
Published: August 2008

AbstractDicer is an evolutionarily conserved ribonuclease III that is necessary for microRNA (miRNA) processing and the synthesis of small interfering RNAs from long double-stranded RNA. Although it has been shown that Dicer plays important roles in the mammalian germline and early embryogenesis, the functions of Dicer-dependent pathways in the somatic cells of the female reproductive tract are unknown. Using a transgenic line in which Cre recombinase is driven by the anti-Müllerian hormone receptor type 2 promoter, we conditionally inactivated Dicer1 in the mesenchyme of the developing Müllerian ducts and postnatally in ovarian granulosa cells and mesenchyme-derived cells of the oviducts and uterus. Deletion of Dicer in these cell types results in female sterility and multiple reproductive defects including decreased ovulation rates, compromised oocyte and embryo integrity, prominent bilateral paratubal (oviductal) cysts, and shorter uterine horns. The paratubal cysts act as a reservoir for spermatozoa and oocytes and prevent embryos from transiting the oviductal isthmus and passing the uterotubal junction to enter the uterus for implantation. Deep sequencing of small RNAs in oviduct revealed down-regulation of specific miRNAs in Dicer conditional knockout females compared with wild type. The majority of these differentially expressed miRNAs are predicted to regulate genes important for Müllerian duct differentiation and mesenchyme-derived structures, and several of these putative target genes were significantly up-regulated upon conditional deletion of Dicer1. Thus, our findings reveal diverse and critical roles for Dicer and its miRNA products in the development and function of the female reproductive tract.
Hormonal regulation of the humoral innate immune response inDrosophila melanogaster
Authors: Flatt Thomas , Heyland Andreas , Rus Florentina , Porpiglia Ermelinda , Sherlock Chris , Yamamoto Rochele , Garbuzov Alina , Palli Subba R. , Tatar Marc , Silverman Neal 
Published: August 2008

SUMMARYJuvenile hormone (JH) and 20-hydroxy-ecdysone (20E) are highly versatile hormones, coordinating development, growth, reproduction and aging in insects. Pulses of 20E provide key signals for initiating developmental and physiological transitions, while JH promotes or inhibits these signals in a stage-specific manner. Previous evidence suggests that JH and 20E might modulate innate immunity, but whether and how these hormones interact to regulate the immune response remains unclear. Here we show that JH and 20E have antagonistic effects on the induction of antimicrobial peptide (AMP)genes in Drosophila melanogaster. 20E pretreatment of Schneider S2* cells promoted the robust induction of AMP genes, following immune stimulation. On the other hand, JH III, and its synthetic analogs (JHa)methoprene and pyriproxyfen, strongly interfered with this 20E-dependent immune potentiation, although these hormones did not inhibit other 20E-induced cellular changes. Similarly, in vivo analyses in adult flies confirmed that JH is a hormonal immuno-suppressor. RNA silencing of either partner of the ecdysone receptor heterodimer (EcR or Usp) in S2* cells prevented the 20E-induced immune potentiation. In contrast, silencing methoprene-tolerant (Met), a candidate JH receptor, did not impair immuno-suppression by JH III and JHa, indicating that in this context MET is not a necessary JH receptor. Our results suggest that 20E and JH play major roles in the regulation of gene expression in response to immune challenge.
Induced cell proliferation in putative haematopoietic tissues of the sea star,Asterias rubens(L.)
Authors: Holm Kristina , Dupont Samuel , Sköld Helen , Stenius Anna , Thorndyke Michael , Hernroth Bodil 
Published: August 2008

SUMMARYThe coelomic fluid of the echinoderm Asterias rubens possesses large populations of circulating coelomocytes. This study aimed to expand the knowledge about the haematopoietic sources of these cells. Injection of the immune-stimulating molecules lipopolysaccharide (LPS) and concanavalin A(ConA) resulted in an increase in coelomocytes. To investigate if these molecules induce cell proliferation in putative haematopoietic tissues (HPTs),short-term exposure of the substitute nucleotide 5-bromo-2′-deoxyuridine(BrdU) was conducted. Immunohistochemical analysis, using fluorescein-labelled antibodies to trace BrdU, showed pronounced cell division in the coelomic epithelium and axial organ. In the pyloric caeca, not considered as an HPT,proliferation was not detected. BrdU labelling of monolayers of cells obtained by collagenase treatment of coelomic epithelium, axial organ and Tiedemann body revealed induced cell proliferation in response to both LPS and ConA while proliferation of pyloric caeca and circulating coelomocytes remained sparse. By using confocal microscopy it was observed that both the morphology and functional behaviour of cells released from explants of coelomic epithelium showed high similarity to those of circulating phagocytes. It was concluded that the increased coelomocyte numbers observed in response to LPS and ConA were reflected in an induced cell proliferation in coelomic epithelium, axial organ and Tiedemann body, which reinforces the idea that these organs are HPTs and the sources of coelomocyte renewal.