Differential CCR5Delta32 allelic frequencies in juvenile idiopathic arthritis subtypes: evidence for different regulatory roles of CCR5 in rheumatological diseases.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood and is characterized by persistent arthritis for at least 6 weeks. Its aetiopathogenesis is unknown but there is strong evidence that there is a substantial genetic component. Chemokine receptors genes are among the candidate genes for association with arthritis and other inflammatory diseases. The CC chemokine receptor 5 (CCR5)Delta32 polymorphism has been associated with rheumatoid arthritis (RA), conferring a protective effect. OBJECTIVE: To determine whether the CCR5Delta32 polymorphism is associated with JIA and RA in Brazilian patients. METHODS: We investigated 203 RA patients, 101 JIA patients, and 104 healthy individuals by amplification of the CCR5Delta32 deletion. We compared the allelic frequencies among these groups, as well as among different JIA subtypes. RESULTS: The frequency of the Delta32 allele was higher in JIA patients (9.4%) as compared to control subjects (3.8%) and RA patients (3.2%). Grouping the patients according to JIA subtypes, we observed a higher CCR5Delta32 allelic frequency in the subtypes with a greater inflammatory component: 4.1% in oligoarticular (n = 49), 11.2% in polyarticular (n = 40) [9.5% in rheumatoid factor negative (RF-) and 33.3% in RF positive (+)], and 25% in systemic JIA (n = 12). CONCLUSIONS: This study suggests that in JIA, unlike in RA, CCR5Delta32 does not have a protective effect, but instead it could be a factor associated with more inflammatory forms of the disease. These observations give rise to new questions about the mechanism and the cellular types involved in JIA as well as about the aetiology of JIA.

The chemokine receptor CCR5 genetic polymorphism and expression in rheumatoid arthritis patients.

OBJECTIVES: To identify the genetic polymorphism of the chemokine receptor CCR5 (the Delta32 allelic variant) in patients with rheumatoid arthritis (RA) and compare the findings with healthy controls. To compare the CCR5 phenotypic expression in T cells and monocytes isolated from the peripheral blood and synovial fluid in a subgroup of RA patients. METHODS: CCR5 genes of 92 RA patients and 160 healthy controls were genotyped using specific primers flanking the region of deletion. The ethnic distribution was similar between the groups. Flow cytometric analysis was used for immunophenotyping the T cells and monocytes isolated from the peripheral blood and synovial fluid of eight RA patients. The isolated cells were triple stained with CD4 or CD8, CD25 and CCR5 monoclonal antibodies. RESULTS: There was no difference in the CCR5Delta32 genotypic frequency between the RA patients and the control group (0.055 and 0.063, respectively, p = 0.989). No homozygote for the CCR5Delta32 allele was seen in either group. Five heterozygotes were identified in the RA patient group, whose disease was shown to be aggressive. A significant enrichment of activated CCR5+ monocytes was seen in the synovial fluid of the RA patients subjected to arthrocentesis, who were all homozygotes for the CCR5 wild-type genotype. CONCLUSION: A protective role for the CCR5 allelic variant in RA development was not observed. Disease severity in the heterozygotes suggests that other proinflammatory mechanisms might overcome this mutation in vivo. The activated CCR5+ monocyte enrichment in the rheumatoid synovial fluid might indicate that this cell population has an important role in the pathogenesis of the disease.

Tratamento cirúrgico de ostema mandibular em gato doméstico (Felis catus) - Relato de caso / Surgical treatment of a mandibular ostema in a domestic cat (Felis catus) - Case report

O osteoma é uma neoplasia benigna de origem osteoblástica, rara em cães e gatos. Clinicamente, pode ser palpado como uma massa firme aderida ao osso, e ao exame radiográfico apresentam-se como uma massa irregular, mal definida e de aparência densa. Este artigo relata o sucesso de uma técnica cirúrgica alternativa, em que uma broca de corte, acoplada à caneta de alta rotação, foi usada para cortar diretamente o tecido gengival e o tecido ósseo na linha do arco mandibular, removendo e/ou destruindo todas as estruturas consideradas anormais.

Interchain disulfide bonds in crotamine self-association.

Crotamine, a basic neurotoxic protein, was isolated from the venom of the Southern Brazilian rattlesnake (Crotalus durissus terrificus) by gel filtration. The isolated protein showed a single band on PAGE at pH 4.5 and 7% (w/v) gel concentration, but two or more bands at 14% gel concentration, even in the presence of 4 M urea. After reduction and carboxymethylation, however, a single band was again detected. SDS-PAGE as well as ultracentrifugal analysis of the native (NC) and of the reduced and carboxymethylated (RCC) crotamine revealed a molecular weight of 4,500-5,000 for RCC and 9,000-10,000 for NC. Both components of a two-band crotamine preparation were isolated by preparative PAGE and characterized. Their particular electrophoretic mobility was retained. Their amino acid composition. N-terminal residue, and apparent toxicity were the same as those of the original sample. It was concluded that crotamine is able to form a dimer of 9,760 Da with two identical polypeptide chains crosslinked by interchain disulfide bonds and a shape not very far from spherical, which covalently binds extra subunits of 4,880 Da each.

Effect of anions on the quaternary structure of Biomphalaria glabrata hemoglobin at pH 3.0

1. The effect of different ions on the state of aggregation of B. glabrata hemoglobin at pH 3.0 was investigated by analytical ultracentrifugation. 2. Low salt concentration induced aggregation of the protein subunits at this pH. There was an exponential dependence of the sedimentation coefficient on salt concentration. 3. The aggregating effect was primarily due to the anion and was abolished when the protein was treated with maleic anhydride. 4. The effectiveness of anions in inducing aggregation was: SO2-4 > SCN- > CH3- COO- > CF3-COO- >CL-. 5. tThe observed phenomena are not explained either by the Debye-Hückel theory or by a disturance of the protein hydration shell

Characterization of the hemoglobin of Biomphalaria glabrata as a glycoprotein.

1. The hemoglobin of Biomphalaria glabrata is a glycoprotein which contains 3% sugars. 2. The sugar moiety is composed of 2 mol of hexose and one mol of hexosamine per mol of monomer. 3. The hexosamine in the molecule is glucosamine. 4. Mannose, galactose and fucose are present in the molecule in a ratio of 2:1:1. 5. No sialic and uronic acids were detected in this hemoglobin.