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121.
Eve Namisango Matthew J. Allsop Richard A. Powell Stefan J. Friedrichsdorf Emmanuel B.K. Luyirika Fatia Kiyange Edward Mukooza Chris Ntege Eunice Garanganga Mavis Ntombifuthi Ginindza-Mdluli Faith Mwangi-Powell Lidia Justino Mondlane Richard Harding 《Journal of pain and symptom management》2018,55(3):851-863
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Cultured adherent human macrophages and a promonocytic cell line, U 937, were previously shown to produce a Mr 95,000 gelatin-binding protein. The protein has no immunologic cross-reactivity with the well- characterized gelatin-binding protein fibronectin and the Mr 70,000 gelatin-binding protein produced by a variety of mesenchymal or epithelial cell types (T. Vartio et al, J Biol Chem 257:8862, 1982). In the present study the Mr 95,000 protein was found in Triton X-100 extracts of granulocytes purified from human blood buffy coat. The protein, as isolated by gelatin-agarose, was immunologically cross- reactive with the corresponding macrophage protein in immunoblotting assay. When peripheral blood and bone marrow cells were examined for the presence of the Mr 95,000 protein by indirect immunofluorescence, positive staining was detected only in differentiated granulocytes but not to any significant extent in metamyelocytes, myelocytes, promyelocytes, or in normal or leukemic blasts. In granulocytes the protein had a granular cytoplasmic distribution. In freshly prepared monocyte cultures, the Mr 95,000 protein was detected in low amounts in the cytoplasm, while along with differentiation of the cells into macrophages, the immunofluorescence increased in a reticular and vesicular cytoplasmic pattern and in a juxtanuclear cap, probably representing the Golgi complex. In conclusion, the Mr 95,000 gelatin- binding protein was specifically detected in macrophages and granulocytes and may thus serve as a differentiation marker for these phagocytic cells. 相似文献
126.
The novel 1,3,4,11b‐tetrahydro‐1H‐fluoreno[9,1‐cd]azepine framework, a structurally rigidified variant of the 1‐phenylbenzazepine template, was synthesized via direct arylation as a key reaction. Evaluation of the binding affinities of the rigidified compounds across a battery of serotonin, dopamine, and adrenergic receptors indicates that this scaffold unexpectedly has minimal affinity for D1 and other dopamine receptors and is selective for the 5‐HT6 receptor. The affinity of these systems at the 5‐HT6 receptor is significantly influenced by electronic and hydrophobic interactions as well as the enhanced rigidity of the ligands. Molecular docking studies indicate that the reduced D1 receptor affinity of the rigidified compounds may be due in part to weaker H‐bonding interactions between the oxygenated moieties on the compounds and specific receptor residues. Key receptor–ligand H‐bonding interactions, salt bridges, and π–π interactions appear to be responsible for the 5‐HT6 receptor affinity of the compounds. Compounds 10 (6,7‐dimethoxy‐2,3,4,11b‐tetrahydro‐1H‐fluoreno[9,1‐cd]azepine) and 12 (6,7‐dimethoxy‐2‐methyl‐2,3,4,11b‐tetrahydro‐1H‐fluoreno[9,1‐cd]azepine) have been identified as structurally novel, high affinity (Ki = 5 nM), selective 5‐HT6 receptor ligands. 相似文献
127.
Clare R. Harding Corinna Mattheis Aurélie Mousnier Clare V. Oates Elizabeth L. Hartland Gad Frankel Gunnar N. Schroeder 《Infection and immunity》2013,81(11):4261-4270
The Dot/Icm type IV secretion system (T4SS) of Legionella pneumophila is crucial for the pathogen to survive in protozoa and cause human disease. Although more than 275 effector proteins are delivered into the host cell by the T4SS, the function of the majority is unknown. Here we have characterized the Dot/Icm effector LtpD. During infection, LtpD localized to the cytoplasmic face of the membrane of the Legionella-containing vacuole (LCV). In A549 lung epithelial cells, ectopically expressed LtpD localized to large vesicular structures that contained markers of endosomal compartments. Systematic analysis of LtpD fragments identified an internal 17-kDa fragment, LtpD471-626, which was essential for targeting ectopically expressed LtpD to vesicular structures and for the association of translocated LtpD with the LCV. LtpD471-626 bound directly to phosphatidylinositol 3-phosphate [PtdIns(3)P] in vitro and colocalized with the PtdIns(3)P markers FYVE and SetA in cotransfected cells. LtpD was also found to bind the host cell enzyme inositol (myo)-1 (or 4)-monophosphatase 1, an important phosphatase involved in phosphoinositide production. Analysis of the role of LtpD in infection showed that LtpD is involved in bacterial replication in THP-1 macrophages, the larvae of Galleria mellonella, and mouse lungs. Together, these data suggest that LtpD is a novel phosphoinositide-binding L. pneumophila effector that has a role in intracellular bacterial replication. 相似文献
128.
Lucy?SelmanEmail author Victoria?Simms Suzanne?Penfold Richard?A?Powell Faith?Mwangi-Powell Julia?Downing Nancy?Gikaara Grace?Munene Irene?J?Higginson Richard?Harding 《BMC palliative care》2013,12(1):35
Background
Despite the huge burden of HIV in sub-Saharan Africa, there is little evidence of the multidimensional needs of patients with HIV infection to inform the person-centred care across physical, psychological, social and spiritual domains stipulated in policy guidance. We aimed to describe the problems experienced by people with HIV in Kenya and Uganda and the management of these problems by HIV outpatient services.Methods
Local researchers conducted in depth qualitative interviews with HIV patients, caregivers and service staff at 12 HIV outpatient facilities (6 in Kenya, 6 in Uganda). Interview data were analysed thematically.Results
189 people were interviewed (83 patients, 47 caregivers, 59 staff). The impact of pain and symptoms and their causes (HIV, comorbidities, treatment side-effects) were described. Staff reported that effective pain relief was not always available, particularly in Kenya. Psychosocial distress (isolation, loneliness, worry) was exacerbated by stigma and poverty, and detrimentally affected adherence. Illness led to despair and hopelessness. Provision of counselling was reported, but spiritual support appeared to be less common. Neither pain nor psychosocial problems were routinely reported to service staff. Collaboration with local hospices and income-generation activities for patients were highlighted as useful.Conclusions
The findings demonstrate the multiple and interrelated problems associated with living with HIV and how psychosocial and spiritual distress can contribute to 'total pain’ in this population. In line with the palliative care approach, HIV care requires holistic care and assessment that take into account psychological, socioeconomic and spiritual distress alongside improved access to pain-relieving drugs, including opioids.129.
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