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Human Trafficking

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3201. Cell Growth Inhibition and Functioning of Human Somatostatin Receptor Type 2 Are Modulated by Receptor Heterodimerization. Full Text available with Trip Pro

Cell Growth Inhibition and Functioning of Human Somatostatin Receptor Type 2 Are Modulated by Receptor Heterodimerization. Somatostatin (SST) analogs have been successfully used in the medical treatment of acromegaly, caused by GH hypersecreting pituitary adenomas. Patients on SST analogs rarely develop tachyphylaxis despite years of continuous administration. It has been recently proposed that a functional association between SST receptor (SSTR) subtypes 2 and 5 exists to account (...) (Kip1) in cells expressing both SSTR2 and SSTR5 compared with SSTR2 alone. Furthermore, cell growth inhibition by L-779,976 treatment was markedly extended in coexpressing cells. Trafficking of SSTR2 is also affected upon heterodimerization, an attribute corresponding to modifications in beta-arrestin association kinetics. Activation of SSTR2 results in the recruitment and stable association of beta-arrestin, followed by receptor internalization and intracellular receptor pooling. In contrast

2008 Molecular Endocrinology

3202. Differential expression of human Dlg in cervical intraepithelial neoplasias. (Abstract)

Differential expression of human Dlg in cervical intraepithelial neoplasias. To evaluate the potential role of human discs large (hDlg) protein in the pathogenesis of cervical neoplasia by examining the changes of hDlg protein expression in normal cervical epithelium as well as various stages of cervical dysplasia.Archived formalin-fixed, paraffin-embedded cervical tissue sections with known status of human Papillomavirus (HPV) infection were examined for hDlg expression using (...) expression are, however, invariable regardless the subtypes of HPV infection of the specimens. In the invasive squamous cell carcinoma, membranous staining of hDlg is reduced or absent with some mitotic cells showing evidence of hDlg accumulation in the midbody zone.These data suggest a functional role of hDlg in the development and progression of cervical neoplasia with implications in cytokinesis, viral trafficking, and metastasis pathways.

2004 Gynecologic Oncology

3203. Isoflurane alters the amount of dopamine transporter expressed on the plasma membrane in humans. (Abstract)

Isoflurane alters the amount of dopamine transporter expressed on the plasma membrane in humans. Isoflurane increases extracellular dopamine concentration and causes trafficking of the dopamine transporter (DAT) in transfected cells. Also, the binding potentials of highly specific positron-emitting DAT ligands are altered by isoflurane in rhesus monkeys. The purpose of this study was to determine the dose-response curve for isoflurane altering the binding potential of one of these ligands ([F (...) -18]FECNT) in humans.Twenty human volunteers underwent positron emission tomography using [F-18]FECNT. All subjects were scanned while awake and then again after assignment to one of four groups (n = 5 each): awake-control, propofol-control, or light or deep isoflurane anesthesia as defined by Bispectral Index monitoring. Bispectral Index values in the light anesthesia group were 40 +/- 7 (end-tidal isoflurane, 1.02 +/- 0.08) versus 27 +/- 10 (end-tidal isoflurane, 1.6 +/- 0.3) in the deep

2004 Anesthesiology

3204. A critical role for vesicle-associated membrane protein-7 in exocytosis from human eosinophils and neutrophils. (Abstract)

) are implicated in exocytosis from human granulocytes. Vesicle-associated membrane proteins-7 and -8 have been implicated in endosome/lysosome trafficking, however, their role in granulocyte exocytosis remains obscure.We sought to investigate the expression and functional role of SNARE isoforms in the secretion of different granule-derived mediators in human eosinophils and neutrophils.The expression of SNAREs was determined by subcellular fractionation and flow cytometry. SNARE-specific antibodies were (...) A critical role for vesicle-associated membrane protein-7 in exocytosis from human eosinophils and neutrophils. Granulocyte exocytosis is proposed to be critically dependent on the interaction of soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNAREs) located on granules/vesicles (v-SNAREs) and plasma membrane (t-SNAREs). Previous studies indicated that the v-SNARE, vesicle-associated membrane protein (VAMP)-2, as well as t-SNAREs (SNAP-23, syntaxin-4 and -6

2006 Allergy

3205. Secretoneurin is released into human airways by topical histamine but not capsaicin. Full Text available with Trip Pro

Secretoneurin is released into human airways by topical histamine but not capsaicin. The neuropeptide secretoneurin, with potential relevance to leukocyte trafficking, is present in nerves of the nasal mucosa in allergic rhinitis and may be released in response to allergen and histamine exposure. There is no information on the occurrence and mechanisms of release of secretoneurin in healthy human airways.The presence of secretoneurin in nasal biopsies and its release in response to nasal (...) . Nasal histamine challenge produced symptoms (P <0.05) and increased the mucosal output of secretoneurin (P <0.05) and fucose (P <0.05). Bronchial histamine challenge increased the sputum levels of secretoneurin (P <0.05).We conclude that secretoneurin is present in healthy human airways and that histamine evokes its release in both nasal and bronchial mucosae. The present observations support the possibility that secretoneurin is involved in histamine-dependent responses of the human airway mucosa.

2005 Allergy

3206. Inflammatory cytokine and thrombin regulation of interleukin-8 and intercellular adhesion molecule-1 expression in first trimester human decidua. Full Text available with Trip Pro

Inflammatory cytokine and thrombin regulation of interleukin-8 and intercellular adhesion molecule-1 expression in first trimester human decidua. Decidual neutrophil infiltration complicates spontaneous abortions associated with inflammation and hemorrhage. Transendothelial neutrophil migration into inflamed tissues involves IL-8-mediated chemoattraction, then neutrophil attachment to endothelial cell-expressed intercellular adhesion molecule-1 (ICAM-1).The aim of this study was to assess IL-8 (...) and ICAM-1 regulation in decidual inflammation and hemorrhage; the effects of the proinflammatory cytokines, TNFalpha, IL-1beta and the hemostatic, proinflammatory cytokine thrombin were measured on IL-8 expression in first trimester decidual cells (DCs), and ICAM-1 immunostaining was compared in normal, inflamed, and hemorrhagic first trimester decidua.Immunohistochemistry of human decidua and in vitro treatment of human decidual cells were performed.The study was conducted at the Academic Medical

2005 Journal of Clinical Endocrinology and Metabolism

3207. Cell surface targeting accounts for the difference in iodide uptake activity between human Na+/I- symporter and rat Na+/I- symporter. Full Text available with Trip Pro

Cell surface targeting accounts for the difference in iodide uptake activity between human Na+/I- symporter and rat Na+/I- symporter. The Na+/I- symporter (NIS) has been proposed to serve as an imaging reporter gene to optimize vector delivery, monitor therapeutic gene expression, and map the tissue/organ sites of repopulated progenitor cells in vivo. In addition, NIS can serve as a therapeutic gene to facilitate targeted radionuclide therapy for various cancers.It was reported that rat NIS (...) (rNIS) confers higher radioactive iodide uptake (RAIU) activity than human NIS (hNIS). We aim to investigate the mechanism underlying this difference.We showed that the open reading frames (ORF) of hNIS and rNIS, although encoding for proteins with 83% amino acid identity, exhibit a significant difference in RAIU activity in transfected cells. The ORF rNIS confers four to five times higher RAIU activity as well as cell surface NIS accumulation than ORF hNIS despite similar total NIS protein levels

2005 Journal of Clinical Endocrinology and Metabolism

3208. The human thyrotropin receptor is predominantly internalized by beta-arrestin 2. Full Text available with Trip Pro

The human thyrotropin receptor is predominantly internalized by beta-arrestin 2. The beta-arrestin-dependent endocytosis of the beta2-adrenergic receptor (beta2AR) has been demonstrated by confocal fluorescence microscopy. Furthermore, a constitutively activated beta2AR is also constitutively desensitized and down-regulated. To clarify the function of beta-arrestin 1 or 2 for TSH receptor (TSHR) desensitization and examine whether constitutively activated TSHR mutants are internalized (...) in a different way, we investigated the TSHR trafficking in association with beta-arrestins in cotransfection experiments in HEK 293 cells using confocal laser-scanning microscopy. We found that both beta-arrestins are able to internalize the TSHR in HEK 293 cells. However, whereas the beta-arrestin 1-mediated TSHR internalization reached its maximum 20 min after TSH stimulation, the beta-arrestin 2-mediated TSHR internalization already reached its maximum 5 min after TSH stimulation. Furthermore

2006 Endocrinology

3209. Expression of fatty-acid-handling proteins in human adipose tissue in relation to obesity and insulin resistance. Full Text available with Trip Pro

Expression of fatty-acid-handling proteins in human adipose tissue in relation to obesity and insulin resistance. Protein-mediated trans-membrane and intracellular fatty acid trafficking are becoming increasingly recognised as biochemically and physiologically important concepts. Obesity and insulin resistance are polygenic disorders, heavily influenced by environmental and life-style factors, and are virtually always associated with disturbed fatty acid metabolism in adipose and other tissues (...) suggest that facilitated fatty acid trafficking is a physiologically and pathologically relevant phenomenon in man.

2004 Diabetologia

3210. Fluvastatin inhibits raft dependent Fcgamma receptor signalling in human monocytes. (Abstract)

Fluvastatin inhibits raft dependent Fcgamma receptor signalling in human monocytes. Statins inhibit HMG-CoA reductase and thus block cholesterol and isoprenoid biosynthesis. Since statins also have anti-inflammatory effects, we investigated the effect of fluvastatin on monocyte Fcgamma receptor function. Fluvastatin (0.5-20 microM) inhibited Fcgamma receptor signal transduction at the level of tyrosine kinase activation, in a time and dose dependent manner. Initiation of tyrosine (...) phosphorylation is not thought to involve prenylated proteins; thus, we hypothesised that fluvastatin might disrupt cholesterol and sphingolipid membrane rafts to impair signalling. Consistent with this hypothesis, fluvastatin decreased (and mevalonate rescued) signalling molecules within membrane rafts in parallel with effects on tyrosine phosphorylation events. Raft integrity was unaffected by prenyl transferase inhibitors. In addition, Fcgamma receptor mediated immune complex trafficking, activation of MAP

2004 Atherosclerosis

3211. Pharmacological regulation of cholesterol efflux in human monocyte-derived macrophages in the absence of exogenous cholesterol acceptors. (Abstract)

and avasimibe in acLDL-loaded cells. ApoE secretion was reduced by drugs affecting cholesterol trafficking but enhanced by LXR/RXR ligands. Incubation with an anti-apoE antibody virtually removed immunodetectable apoE from the medium, significantly increasing cholesterol storage and decreasing efflux. These findings indicate that in human macrophages spontaneous cholesterol efflux: (i) is not necessarily promoted by increasing intracellular free cholesterol, (ii) is increased by compounds that activate (...) Pharmacological regulation of cholesterol efflux in human monocyte-derived macrophages in the absence of exogenous cholesterol acceptors. Cholesterol efflux from human monocyte-derived macrophages in the absence of exogenous acceptors has been described, but is unclear in mechanism. We investigated this process in relation to the expression of relevant genes, intracellular cholesterol storage and apoE secretion using drugs affecting different aspects of cholesterol metabolism. Both natural (22R

2005 Atherosclerosis

3212. Epidermal stem cells are the source of sweat glands in human fetal skin: evidence of synergetic development of stem cells, sweat glands, growth factors, and matrix metalloproteinases. (Abstract)

Epidermal stem cells are the source of sweat glands in human fetal skin: evidence of synergetic development of stem cells, sweat glands, growth factors, and matrix metalloproteinases. The development of sweat glands is a complex biological process, and the extent of cellular trafficking between epidermal stem cells and the development of sweat glands is uncertain. Therefore, we studied the synergetic development effects of stem cells, sweat glands, growth factors, and matrix metalloproteinases (...) (MMPs) in human skin. Human fetal skin was obtained from spontaneously aborted fetuses at 11-31 weeks of gestation. Paraffin sections were cut and stained with hematoxylin and eosin or immunostained with antibodies against beta(1) integrin, keratin (K)-19 and K7, MMP-2 and -7, and epidermal growth factor. In situ hybridization was used along with semiquantitative analysis of the positive expression of these proteins to analyze for mRNA expression of MMP-2 and -7. Histological studies revealed

2005 Wound Repair and Regeneration

3213. Avian influenza virus infections in humans. Full Text available with Trip Pro

circulating A/H5N1 genotype Z virus has since been spreading from Southern China to other parts of the world. Migratory birds and, less likely, bird trafficking are believed to be globalizing the avian influenza A/H5N1 epidemic in poultry. More than 200 human cases of avian influenza virus infection due to A/H5, A/H7, and A/H9 subtypes mainly as a result of poultry-to-human transmission have been reported with a > 50% case fatality rate for A/H5N1 infections. A mutant or reassortant virus capable (...) Avian influenza virus infections in humans. Seroepidemiologic and virologic studies since 1889 suggested that human influenza pandemics were caused by H1, H2, and H3 subtypes of influenza A viruses. If not for the 1997 avian A/H5N1 outbreak in Hong Kong of China, subtype H2 is the likely candidate for the next pandemic. However, unlike previous poultry outbreaks of highly pathogenic avian influenza due to H5 that were controlled by depopulation with or without vaccination, the presently

2006 Chest

3214. ATP release mediates fluid flow-induced proliferation of human bone marrow stromal cells. (Abstract)

ATP release mediates fluid flow-induced proliferation of human bone marrow stromal cells. Oscillatory fluid flow induced the vesicular release of ATP from human BMSCs that directly contributes to the induction of BMSC proliferation. Degrading extracellular nucleotides prevents fluid flow-induced increases in intracellular calcium concentration, the activation of calcineurin, and the nuclear translocation of NFAT.Regulation of bone cell activity by autocrine/paracrine factors is a well (...) fluid flow, and the concentration of ATP in conditioned media samples was determined using a luciferin:luciferase-based reaction. Western blot analysis was used to examine the expression of purinergic receptors. Using pharmacological antagonists of gap junction hemichannels and vesicular trafficking, we studied the mechanism of ATP release from BMSCs. Apyrase was used to study the effect of extracellular nucleotides on intracellular calcium concentration, calcineurin activity, and nuclear factor

2007 Journal of Bone and Mineral Research

3215. Lentiviral-Transduced Human Mesenchymal Stem Cells Persistently Express Therapeutic Levels of Enzyme in a Xenotransplantation Model of Human Disease Full Text available with Trip Pro

the secondary elevation of other lysosomal enzymes and reduce lysosomal distention in several tissues. In addition, at least one physiologic marker of disease, retinal function, was normalized following transplantation of MSCs-GUSB. These data provide evidence that transduced human MSCs retain their normal trafficking ability in vivo and persist for at least 4 months, delivering therapeutic levels of protein in an authentic xenotransplantation model of human disease. (...) Lentiviral-Transduced Human Mesenchymal Stem Cells Persistently Express Therapeutic Levels of Enzyme in a Xenotransplantation Model of Human Disease Bone marrow-derived mesenchymal stem cells (MSCs) are a promising platform for cell- and gene-based treatment of inherited and acquired disorders. We recently showed that human MSCs distribute widely in a murine xenotransplantation model. In the current study, we have determined the distribution, persistence, and ability of lentivirally transduced

2008 Stem cells (Dayton, Ohio)

3216. CD4-Independent Infection of Astrocytes by Human Immunodeficiency Virus Type 1: Requirement for the Human Mannose Receptor Full Text available with Trip Pro

siRNA blocked HIV-1 infection in human primary astrocytes. In agreement with these findings, hMR bound to HIV-1 virions via the abundant and highly mannosylated sugar moieties of HIV-1 envelope glycoprotein gp120 in a Ca(2+)-dependent fashion. Moreover, hMR-mediated HIV-1 infection was dependent upon endocytic trafficking as assessed by transmission electron microscopy, as well as inhibition of viral entry by endosomo- and lysosomotropic drugs. Taken together, these results demonstrate the direct (...) CD4-Independent Infection of Astrocytes by Human Immunodeficiency Virus Type 1: Requirement for the Human Mannose Receptor Human immunodeficiency virus type 1 (HIV-1) infection occurs in the central nervous system and causes a variety of neurobehavioral and neuropathological disorders. Both microglia, the residential macrophages in the brain, and astrocytes are susceptible to HIV-1 infection. Unlike microglia that express and utilize CD4 and chemokine coreceptors CCR5 and CCR3 for HIV-1

2004 Journal of virology

3217. Human immunodeficiency virus gp120-induced apoptosis of human neuroblastoma cells in the absence of CXCR4 internalization Full Text available with Trip Pro

or oligomeric, in presence or absence of soluble CD4) did not change CXCR4 membrane levels. Similar results were obtained in a murine lymphocyte cell line (300-19) stably expressing human CXCR4. Nevertheless, gp120IIIB was still able to activate intracellular signaling and proapoptotic pathways, via CXCR4. These results show that gp120IIIB toxicity and signaling do not require CXCR4 internalization in SH-SY5Y cells, and suggest that the viral protein may alter normal CXCR4 trafficking thus, interfering (...) Human immunodeficiency virus gp120-induced apoptosis of human neuroblastoma cells in the absence of CXCR4 internalization The chemokine receptor CXCR4 functions as human immunodeficiency virus (HIV)-1 coreceptor and is involved in acquired immunodeficiency virus (AIDS) neuropathogenesis. CXCR4 is expressed by most cell types in the brain, including microglia, astrocytes, and neurons. Studies have shown that the HIV envelope protein gp120 binds to neuronal CXCR4 and activates signal transduction

2006 Journal of neurovirology

3218. Activation of human CD4+ T cells by targeting MHC class II epitopes to endosomal compartments using human CD1 tail sequences Full Text available with Trip Pro

the different CD1 cytoplasmic tail sequences could optimally target antigens to the MHC class II antigen presentation pathway. Evaluation of trafficking patterns revealed that all four human CD1-derived targeting sequences delivered antigen to the MHC class II antigen presentation pathway, to early/recycling, early/sorting and late endosomes/lysosomes. There was a preferential requirement for different CD1 targeting sequences for the optimal presentation of an MHC class II epitope in the following hierarchy (...) Activation of human CD4+ T cells by targeting MHC class II epitopes to endosomal compartments using human CD1 tail sequences Distinct CD4(+) T-cell epitopes within the same protein can be optimally processed and loaded into major histocompatibility complex (MHC) class II molecules in disparate endosomal compartments. The CD1 protein isoforms traffic to these same endosomal compartments as directed by unique cytoplasmic tail sequences, therefore we reasoned that antigen/CD1 chimeras containing

2007 Immunology

3219. HIV prevalence and predictors of infection in sex-trafficked Nepalese girls and women. Full Text available with Trip Pro

HIV prevalence and predictors of infection in sex-trafficked Nepalese girls and women. Sex trafficking of girls and women is widespread across South Asia and is recognized as both a violent gender-based crime and major human rights violation. Inadequate empirical data exist to characterize this phenomenon and its related health consequences, such as human immunodeficiency virus (HIV) infection.To determine the prevalence of HIV infection among repatriated sex-trafficked Nepalese girls and women (...) and to identify trafficking-related predictors of such infection.Medical and case records of 287 repatriated girls and women reporting being trafficked from Nepal for sexual exploitation and receiving rehabilitative services between January 1997 and December 2005 at a major nongovernmental organization were systematically reviewed in January 2006.Major Nepalese nongovernmental organization providing shelter and care to repatriated survivors of sex trafficking.Prevalence of and risk for HIV based

2007 JAMA

3220. A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system. Full Text available with Trip Pro

A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system. Phosphoinositide (PI) 3-kinases have been characterized as enzymes involved in receptor signal transduction in mammalian cells and in a complex which mediates protein trafficking in yeast. PI 3-kinases linked to receptors with intrinsic or associated tyrosine kinase activity are heterodimeric proteins, consisting of p85 adaptor and p110 catalytic subunits, which can generate the 3 (...) of 150 kDa, as detected by immunoprecipitation from human cells. Protein sequence analysis and cDNA cloning show that this 150 kDa protein is highly homologous to Vps15p, a 160 kDa protein serine/threonine kinase associated with yeast Vps34p. These results suggest that the major components of the yeast Vps intracellular trafficking complex are conserved in humans.

1995 The EMBO journal

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