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1.
Cell Immunol ; 258(2): 115-22, 2009.
Article in English | MEDLINE | ID: mdl-19426966

ABSTRACT

The Gi protein associated A(3) adenosine receptor (A(3)AR) was recently defined as a novel anti-inflammatory target. The aim of this study was to look at A(3)AR expression levels in peripheral blood mononuclear cells (PBMCs) of patients with autoimmune inflammatory diseases and to explore transcription factors involved receptor expression. Over-expression of A(3)AR was found in PBMCs derived from patients with rheumatoid arthritis (RA), psoriasis and Crohn's disease compared with PBMCs from healthy subjects. Bioinformatics analysis demonstrated the presence of DNA binding sites for nuclear factor-kappaB (NF-kappaB) and cyclic AMP-responsive element binding protein (CREB) in the A(3)AR gene promoter. Up-regulation of NF-kappaB and CREB was found in the PBMCs from patients with RA, psoriasis and Crohn's disease. The PI3K-PKB/Akt signaling pathway, known to regulate both the NF-kappaB and CREB, was also up-regulated in the patients' PBMCs. Taken together, NF-kappaB and CREB are involved with the over-expression of A(3)AR in patients with autoimmune inflammatory diseases. The receptor may be considered as a specific target to combat inflammation.


Subject(s)
Arthritis, Rheumatoid/metabolism , Crohn Disease/metabolism , Psoriasis/metabolism , Receptor, Adenosine A3/biosynthesis , Adult , Cells, Cultured , Cyclic AMP Response Element-Binding Protein/genetics , Humans , I-kappa B Kinase/metabolism , Leukocytes, Mononuclear/metabolism , Middle Aged , NF-kappa B/metabolism , Promoter Regions, Genetic/physiology , Protein Binding , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Messenger/genetics , Receptor, Adenosine A3/genetics , Tumor Suppressor Proteins , Up-Regulation
2.
Rheumatol Int ; 26(11): 1010-3, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16596379

ABSTRACT

Giant cell arteritis/temporal arteritis (GCA/TA) and polymyalgia rheumatica (PMR) are closely related conditions that affect middle age and older patients and frequently occur together. Many authorities consider them to be different phases of the same disease. A study was undertaken of the possible contribution of gallium-67 ((67)Ga) single photon emission tomography (SPECT) scintigraphy to the diagnosis of GCA/TA and PMR, and to support the possible hypothesis of vasculitic nature of PMR. Nine consecutive patients with PMR, and nine consecutive patients with GCA/TA were included in the study. All patients fulfilled the American College of Rheumatology criteria for GCA/TA and Healey's criteria for PMR. The control patients group consisted of those who underwent (67)Ga scintigraphy for febrile illness. All patients and controls underwent (67)Ga SPECT scan of the skull on a dual-head Helix gamma camera 2 days after I.V. injection of 8-10 mCi of (67)Ga citrate. (67)Ga uptake ratio of temporal bone region to bone out of temporal area (TR/Bone) was estimated on transaxial and coronary slices after SPECT scan reconstruction. For each patient and control the calculations of both temporal areas were done. All GCA/TA and PMR patients showed increased uptake in both temporal areas of the skull, while (67)Ga uptake among GCA/TA was the highest, 1.31+/-0.14 in tranaxial view and 1.47+/-0.16 in coronary view. (67)Ga uptake among PMR patients was lower, 1.19+/-0.11 and 1.28+/-0.13, respectively. In comparison, the control patients showed the lowest (67)Ga uptake, 1.04+/-0.09 in transaxial view and 1.11+/-0.06 in coronary view. The results differ significantly between the three groups. It seems that (67)Ga SPECT scan may become a useful tool in the investigation of patients with suspicion of GCA/TA and PMR. Our findings of the increased (67)Ga uptake in the temporal areas among PMR patients add new arguments for vasculitic nature of this disorder.


Subject(s)
Gallium Radioisotopes , Giant Cell Arteritis/diagnostic imaging , Polymyalgia Rheumatica/diagnostic imaging , Aged , Aged, 80 and over , Female , Gallium Radioisotopes/pharmacokinetics , Humans , Male , Middle Aged , Temporal Bone/diagnostic imaging , Tomography, Emission-Computed, Single-Photon
3.
Ann Rheum Dis ; 62(3): 257-60, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12594115

ABSTRACT

BACKGROUND: Temporal arteritis (TA) is a common syndrome in the elderly, consisting of persistent pain in the temporal area of the skull, jaw claudication, sudden visual loss, high erythrocyte sedimentation rate, and tenderness on palpation in the temporal area. The diagnosis of this condition is relatively straightforward when the typical symptoms and a positive temporal artery biopsy are present. However, only half of the patients have a positive temporal artery biopsy. Other diagnostic procedures, such as colour Doppler sonography or superficial carotid artery angiography which have been proved to be useful for the diagnosis of TA, do not discriminate between inflammatory and non-inflammatory temporal artery disease and may be helpful only in experienced hands. Gallium-67 ((67)Ga) planar scan was reported to be useful in the diagnosis of the disease. Quantitative (67)Ga single photon emission computed tomography (SPECT) may raise the accuracy of the diagnosis. OBJECTIVE: To investigate the effectiveness and usefulness of (67)Ga SPECT scintigraphy in the diagnosis of TA. METHODS: Nine patients (five male, four female) and six controls were included in the study. All of them received 8-10 mCi (67)Ga intravenously 48 hours before the scan.(67)Ga uptake ratios were calculated on transaxial and coronal slices. RESULTS: All patients showed increased uptake in the temporal area of the skull compared with controls. CONCLUSION: The data suggest that (67)Ga skull SPECT may be useful in the diagnosis of TA, especially if the uptake ratio in the area of interest is calculated. Further studies are needed to confirm these data.


Subject(s)
Gallium Radioisotopes , Giant Cell Arteritis/diagnostic imaging , Tomography, Emission-Computed, Single-Photon/methods , Aged , Aged, 80 and over , Cineradiography , Female , Gallium Radioisotopes/pharmacokinetics , Humans , Male , Middle Aged , Temporal Bone/diagnostic imaging , Temporal Bone/metabolism
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