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Human Trafficking

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3201. Characterization of the Immune Status of CD8+ T Cells in Oral Lesions of Human Immunodeficiency Virus-Infected Persons with Oropharyngeal Candidiasis Full Text available with Trip Pro

Characterization of the Immune Status of CD8+ T Cells in Oral Lesions of Human Immunodeficiency Virus-Infected Persons with Oropharyngeal Candidiasis Oropharyngeal candidiasis (OPC) remains the most common oral infection in human immunodeficiency virus (HIV) disease. In a high percentage of HIV(+) persons with reduced CD4(+) T cells, oral lesions with Candida present at the outer epithelium have an accumulation of CD8(+) T cells at the epithelium-lamina propria interface associated with reduced (...) expression of the mucosal cell-trafficking adhesion molecule E-cadherin. The purpose of the present study was to characterize the immune status of these CD8(+) T cells. Immunohistochemical staining for phenotypic and activation and costimulation markers was performed on frozen biopsy tissue sections from HIV(+) OPC(+) persons with accumulated CD8(+) T cells. CD8(+) T cells consisted primarily of central memory cells by virtue of positive CD45RO (memory) and CD27 (central memory) expression. However

2006 Clinical and Vaccine Immunology

3202. Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in human glioma Full Text available with Trip Pro

Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in human glioma Significant work in animal models combined with compelling studies in human patients together have begun to provide a higher resolution picture of how the immune system regulates cancer development. Currently, this immune system-tumor interaction is represented by the concept of cancer immunoediting, which emphasizes that immunity may subserve either classical cancer immunosurveillance functions or promote (...) the eventual outgrowth of immunoevasive cancer cells. One important line of evidence supporting an immunosurveillance process in humans has been the finding that the presence of distinct profiles of TILs may be correlated with improved clinical outcomes in a subset of human cancers. However, the contribution of TILs to the natural history of gliomas is less clear. Moreover, understanding the relationship between TILs and cancers of the brain is particularly challenging because our understanding of how

2007 Cancer Immunity : a Journal of the Academy of Cancer Immunology

3203. ATP7B Expression in Human Breast Epithelial Cells Is Mediated by Lactational Hormones Full Text available with Trip Pro

epithelial cells and a diffuse location in lactating tissue. ATP7B protein was present in a different subset of vesicles from those containing milk proteins and did not overlap with Menkes ATPase, ATP-7A, except in the perinuclear region of cells. In the cultured human mammary line, PMC42-LA, treatment with lactational hormones induced a redistribution of ATP7B from a perinuclear region to a region adjacent, but not coincident with, the apical plasma membrane. Trafficking of ATP7B was copper dependent (...) ATP7B Expression in Human Breast Epithelial Cells Is Mediated by Lactational Hormones A role for the copper transporter, ATP7B, in secretion of copper from the human breast into milk has previously not been reported, although it is known that the murine ortholog of ATP7B facilitates copper secretion in the mouse mammary gland. We show here that ATP7B is expressed in luminal epithelial cells in both the resting and lactating human breast, where it has a perinuclear localization in resting

2008 Journal of Histochemistry and Cytochemistry

3204. Chaperone displacement from mutant cystic fibrosis transmembrane conductance regulator restores its function in human airway epithelia Full Text available with Trip Pro

of its maturation, trafficking and regulated anion channel activity in human airway epithelial cells. Thus, PTD-mediated DeltaFRD fragment delivery may provide a therapy for CF. (...) Chaperone displacement from mutant cystic fibrosis transmembrane conductance regulator restores its function in human airway epithelia Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF). The most common mutation, DeltaF508, omits the phenylalanine residue at position 508 in the first nucleotide binding domain (NBD1) of CFTR. The mutant protein is retained in the endoplasmic reticulum and degraded by the ubiquitin-proteasome system. We

2008 The FASEB Journal

3205. A splice site mutation in hERG leads to cryptic splicing in human long QT syndrome Full Text available with Trip Pro

A splice site mutation in hERG leads to cryptic splicing in human long QT syndrome Mutations in the human ether-a-go-go-related gene (hERG) cause type 2 long QT syndrome. In this study, we investigated the pathogenic mechanism of the hERG splice site mutation 2398+1G>C and the genotype-phenotype relationship of mutation carriers in three unrelated kindreds with long QT syndrome. The effect of 2398+1G>C on mRNA splicing was studied by analysis of RNA isolated from lymphocytes of index patients (...) blot and immunostaining studies showed that the mutant expressed an immature form of hERG protein that failed to reach the plasma membrane. Coexpression of the mutant and wild-type channels led to a dominant negative suppression of wild-type channel function by intracellular retention of heteromeric channels. Our results demonstrate that 2398+1G>C activates a cryptic site and generates a full-length hERG protein with an insertion of 18 amino acids, which leads to a trafficking defect of the mutant

2008 Journal of Molecular and Cellular Cardiology

3206. Impact Of Pro Segments On The Folding And Function Of Human Neutrophil α-Defensins Full Text available with Trip Pro

Impact Of Pro Segments On The Folding And Function Of Human Neutrophil α-Defensins Human neutrophil alpha-defensins (HNPs) are synthesized in vivo as inactive precursor proteins, i.e. preproHNPs. A series of sequential proteolytic events excise the N-terminal inhibitory pro peptide, leading to defensin maturation and storage in azurophilic granules. The anionic pro peptide, required for correct sub-cellular trafficking and sorting of proHNPs, inhibits the antimicrobial activity of cationic

2007 Journal of Molecular Biology

3207. A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation. (Abstract)

A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation. Leukocyte function associated antigen-1 (LFA-1) has a multifaceted role in the immune response, including adhesion and trafficking of leukocytes, stabilizing the immune synapse of the MHC-TCR complex and providing costimulation signals. Monoclonal antibodies to the CD11a chain of LFA-1 have been seen to result in effective immunosuppression in experimental models (...) . Efalizumab, a humanized IgG1 anti-CD11a, is approved for use in psoriasis and may provide effective immunosuppression in organ transplantation. Thirty-eight patients undergoing their first living donor or deceased renal transplant were randomized to receive efalizumab 0.5 or 2 mg/kg weekly subcutaneously for 12 weeks. Patients were maintained on full dose cyclosporine, mycophenolate mofetil and steroids or half dose cyclosporine, sirolimus and prednisone. At 6 months following transplant patient survival

2007 American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Controlled trial quality: uncertain

3208. Human blood neutrophil responses to prolonged exercise with and without a thermal clamp. Full Text available with Trip Pro

Human blood neutrophil responses to prolonged exercise with and without a thermal clamp. The purpose of this study was to investigate the effects of prolonged exercise with and without a thermal clamp on neutrophil trafficking, bacterial-stimulated neutrophil degranulation, stress hormones, and cytokine responses. Thirteen healthy male volunteers (means +/- SE: age 21 +/- 1 yr; mass 74.9 +/- 2.1 kg; maximal oxygen uptake 58 +/- 1 ml x kg(-1) x min(-1)) completed four randomly assigned, 2-h (...) response. These results show a similar neutrophilia and decrease in neutrophil degranulation after prolonged exercise with and without a thermal clamp. As such, the rise in core body temperature does not appear to mediate neutrophil trafficking and degranulation responses to prolonged exercise. In addition, these results suggest a limited role for cortisol, granulocyte-colony stimulating factor, and IL-6 in the observed neutrophil responses to prolonged exercise.

2008 Journal of applied physiology (Bethesda, Md. : 1985) Controlled trial quality: uncertain

3209. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Full Text available with Trip Pro

Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Chemotactic cytokines, referred to as chemokines, play an important role in leukocyte trafficking. The circulating levels of chemokines have been shown to increase in inflammatory processes including obesity-related pathologies (e.g. atherosclerosis and diabetes). However, little is currently known about the relationship between chemokines and human obesity. In the present

2006 International Journal of Obesity

3210. Characterization of relaxin receptor (RXFP1) desensitization and internalization in primary human decidual cells and RXFP1 transfected HEK293 cells. Full Text available with Trip Pro

Characterization of relaxin receptor (RXFP1) desensitization and internalization in primary human decidual cells and RXFP1 transfected HEK293 cells. We report here the desensitization and internalization of the relaxin receptor (RXFP1) after agonist activation in both primary human decidual cells and HEK293 cells stably transfected with RXFP1. The importance of beta-arrestin 2 in these processes has also been demonstrated. Thus, in HEK-RXFP1 cells the desensitization of RXFP1 was significantly (...) increased when beta-arrestin 2 was overexpressed. After relaxin activation, beta-arrestin 2 was translocated to the cell membrane and RXFP1 underwent rapid internalization. We have previously shown that RXFP1 forms dimers/oligomers during its biosynthesis and trafficking to the plasma membrane, we now show that internalization of RXFP1 occurs through this dimerization/oligomerization. In nonagonist stimulated cells, it is known that the majority of the RXFP1 is located intracellularly and was confirmed

2008 Endocrinology

3211. Human innate immune responses to hexamethylene diisocyanate (HDI) and HDI-albumin conjugates. Full Text available with Trip Pro

Human innate immune responses to hexamethylene diisocyanate (HDI) and HDI-albumin conjugates. Isocyanates, a leading cause of occupational asthma, are known to induce adaptive immune responses; however, innate immune responses, which generally precede and regulate adaptive immunity, remain largely uncharacterized.The aim of the study was to identify and characterize the cellular, molecular and systemic innate immune responses induced by hexamethylene diisocyanate (HDI).Human peripheral blood (...) mononuclear cells (PBMCs) were stimulated in vitro with HDI-albumin conjugates or control antigen, and changes in phenotype, gene and protein expression were characterized by flow cytometry, microarray, Western blot and ELISA. Cell uptake of isocyanate was visualized microscopically using HDI-albumin conjugates prepared with fluorescently labelled albumin. In vivo, human HDI exposure was performed via a specific inhalation challenge, and subsequent changes in PBMCs and serum proteins were measured by flow

2008 Clinical and Experimental Allergy

3212. Human Eosinophils Show Chemotaxis to Lymphoid Chemokines and Exhibit Antigen-Presenting-Cell-Like Properties upon Stimulation with IFN-gamma, IL-3 and GM-CSF. (Abstract)

that regulates their trafficking to LNs is not yet fully explored. Here, we report that a human eosinophilic leukemia cell line, EoL-1, and human peripheral blood (PB) eosinophils become reactive to the lymphoid chemokines CCL21 and CCL25 upon stimulation.EoL-1 cells were differentiated with dibutyryl cyclic AMP (dEoL-1) and subsequently pulsed with IFN-gamma, IL-3 and GM-CSF. The eosinophil fraction was purified from normal human adult PB and incubated for 1 day with the same cytokine combination.Upon (...) Human Eosinophils Show Chemotaxis to Lymphoid Chemokines and Exhibit Antigen-Presenting-Cell-Like Properties upon Stimulation with IFN-gamma, IL-3 and GM-CSF. Eosinophils are multifunctional leukocytes. Under physiological conditions, they circulate in the blood and through the tissues to serve their functions. In certain inflammatory states, they enter the T-cell areas of lymph nodes (LNs) that drain the inflamed tissue and communicate with T cells in LNs, but the underlying mechanism

2008 International Archives of Allergy and Immunology

3213. Four and a Half LIM Protein 1: A Partner for KCNA5 in Human Atrium. Full Text available with Trip Pro

Four and a Half LIM Protein 1: A Partner for KCNA5 in Human Atrium. Protein-protein interactions are critical for the normal membrane trafficking, localization, and function of voltage-gated ion channels. In human heart, the Shaker-related voltage-gated K(+) channel KCNA5 alpha-subunit forms the major basis of an atrial-specific, ultra-rapid delayed rectifier K(+) current, I(Kur). We sought to identify proteins that interact with KCNA5 in human atrium and investigate their role in the I(Kur (...) ) complex.Using a glutathione-S-transferase (GST)-KCNA5 C-terminal fusion protein and mass spectrometry-based methods, the scaffolding protein four and a half LIM (for Lin-11, Isl-1, and Mec3) protein 1 (FHL1) was identified as a potential protein partner for KCNA5. Immunoprecipitation experiments confirmed a physical interaction of FHL1 with the K(+) channel complex in human atrium, as well as in Chinese hamster ovary (CHO) cells transfected with both KCNA5 and FHL1. In cotransfected cells, confocal

2008 Cardiovascular Research

3214. CLONING, EXPRESSION AND FUNCTIONAL CHARACTERIZATION OF RELAXIN RECEPTOR (LGR7) SPLICE VARIANTS FROM HUMAN FETAL MEMBRANES. Full Text available with Trip Pro

CLONING, EXPRESSION AND FUNCTIONAL CHARACTERIZATION OF RELAXIN RECEPTOR (LGR7) SPLICE VARIANTS FROM HUMAN FETAL MEMBRANES. The relaxin receptor [leucine-rich repeat-containing G protein-coupled receptor 7 (LGR7)] belongs to the leucine-rich repeat containing G protein-coupled receptors subgroup C. Three new LGR7 splice variants have been cloned from the human fetal membranes and shown to be truncated versions of the full-length receptor, encoded by different lengths of the extracellular domain (...) decreased this by the formation of heterodimers with the WT-LGR7, supporting the view that homodimerization is a prerequisite for receptor trafficking to the cell surface. These data suggest that the dominant-negative effects of the LGR7 splice variants expressed in the chorion and decidua could be functionally significant in the peripartal period by inhibiting the function of WT-LGR7 and dampening the responsiveness of these tissues to endogenous relaxin.

2007 Endocrinology

3215. The stress of birth enhances in vitro spontaneous and IL-8-induced neutrophil chemotaxis in the human newborn. (Abstract)

The stress of birth enhances in vitro spontaneous and IL-8-induced neutrophil chemotaxis in the human newborn. The birth process induces fetal stress. Stress has profound effects on the immune system, also by acting on the trafficking of leukocytes, a process in which adhesion and chemotaxis are primordial and critical events for the development of effective antimicrobial defenses. The newborn is rapidly challenged by a microflora at the epithelia linings and therefore depending on early

2007 Pediatric Allergy and Immunology

3216. Expression of neuregulin 1, a member of the epidermal growth factor family, is expressed as multiple splice variants in the adult human cornea. Full Text available with Trip Pro

Expression of neuregulin 1, a member of the epidermal growth factor family, is expressed as multiple splice variants in the adult human cornea. To determine whether neuregulin 1 (Nrg-1) is expressed in the normal adult human cornea.cDNA for Nrg-1 was obtained by direct amplification of RNA isolated from human corneal cell cultures. After sequencing, the likely exon/intron structure was determined by comparison to genomic sequence. RNA was purified from isolated corneal epithelium, corneal (...) that Nrg-1 and its receptor are expressed in adult corneal tissue and cultured cells derived from this tissue. qPCR suggested that epithelial cells and stromal cells produce equivalent levels of Nrg-1, but distinct variants were present that differ in proportion with each source of RNA.Eight distinct forms of Nrg-1 were expressed in the adult human cornea that differ by the alternate use of four exons. This altered the predicted coding sequence in three domains of Nrg-1. These domains are known

2004 Investigative Ophthalmology & Visual Science

3217. Evidence that protease activated receptor 2 expression is enhanced in human coronary atherosclerotic lesions. Full Text available with Trip Pro

in oxLDL epitopes in the coronary artery.This study shows for the first time that PAR-2 expression is enhanced in human coronary atherosclerotic lesions, and suggests that PAR-2 dependent cellular trafficking may be one of the regulatory signalling responses to vascular injury. Further pharmacological studies will establish whether modulation (and in which direction) of PAR-2 represents a possible therapeutic target for controlling the vascular response to injury. (...) Evidence that protease activated receptor 2 expression is enhanced in human coronary atherosclerotic lesions. To investigate protease activated receptor 2 (PAR-2) expression in human coronary atherosclerotic lesions because PAR-2 is involved in the modulation of inflammatory events and vascular function.An immunohistochemical analysis was performed on serial arterial sections, using the following antibodies: MDA2, a murine monoclonal antibody against malondialdehyde lysine epitopes of oxidised

2004 Journal of Clinical Pathology

3218. Radioimmunotherapy with alpha-particle emitting 213Bi-C-functionalized trans-cyclohexyl-diethylenetriaminepentaacetic acid-humanized 3S193 is enhanced by combination with paclitaxel chemotherapy. Full Text available with Trip Pro

Radioimmunotherapy with alpha-particle emitting 213Bi-C-functionalized trans-cyclohexyl-diethylenetriaminepentaacetic acid-humanized 3S193 is enhanced by combination with paclitaxel chemotherapy. Previous experience in solid tumor radioimmunotherapy studies has indicated that greatest therapeutic efficacy is achieved in the treatment of small-volume disease. alpha-Particle-emitting radioisotopes possess several physical characteristics ideally suited to the treatment of minimal residual disease (...) . Therefore, we have investigated the efficacy of the alpha-particle-emitting bismuth-213 (213Bi) radioimmunotherapy using the humanized anti-Lewis Y (Ley) monoclonal antibody humanized 3S193 (hu3S193).The intracellular localization of hu3S193 in Ley-positive MCF-7 breast carcinoma cells was assessed by confocal microscopy. Cytotoxicity of 213Bi-hu3S193 and apoptosis was assessed using [3H]thymidine incorporation assay and ELISA, respectively. Immunoblotting for gamma-H2AX assessed DNA strand breaks

2007 Clinical Cancer Research

3219. A constitutively active mutant of the human lutropin receptor (hLHR-L457R) escapes lysosomal targeting and degradation. Full Text available with Trip Pro

A constitutively active mutant of the human lutropin receptor (hLHR-L457R) escapes lysosomal targeting and degradation. Using biochemical and imaging approaches, we examined the postendocytotic fate of the complex formed by human choriogonadotropin (hCG) and a constitutively active mutant of the human lutropin receptor (hLHR-L457R) found in a boy with precocious puberty and Leydig cell hyperplasia. After internalization, some of the complex formed by the hLHR-wild type (hLHR-wt) and hCG (...) -terminal tail at residue 682 greatly enhances the lysosomal accumulation of the hormone-receptor complexes formed by the hLHR-wt or the L457R mutant, the degradation of the internalized hormone, and the loss of cell surface receptors. The degradation of the hormone internalized by these mutants as well as the loss of cell surface receptors is largely prevented by leupeptin. These results highlight a previously unrecognized complexity in the postendocytotic trafficking of the hLHR and document a clear

2006 Molecular Endocrinology

3220. Evidence that palmitoylation of carboxyl terminus cysteine residues of the human luteinizing hormone receptor regulates postendocytic processing. Full Text available with Trip Pro

Evidence that palmitoylation of carboxyl terminus cysteine residues of the human luteinizing hormone receptor regulates postendocytic processing. Palmitoylation is a well-conserved posttranslational modification among members of the G protein-coupled receptor superfamily. The present study examined the role of palmitoylation in endocytosis and postendocytic trafficking of the human LH receptor (LHR). Palmitoylation of the LHR was determined by incorporation of [3H]palmitic acid into wild-type (...) , not the rate of internalization, determines the efficiency of recycling. The present study shows that palmitoylation of cysteine residues 643 and 644 of the human LHR is a determinant of recycling.

2005 Molecular Endocrinology

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