Fc gamma receptor IIIb polymorphism and systemic lupus erythematosus: association with disease susceptibility and identification of a novel FCGR3B*01 variant.

OBJECTIVE: The objective of this study was to evaluate the association between Fc gamma receptor IIIb polymorphism and susceptibility to systemic lupus erythematosus and clinical traits of the disease. METHODS: Genomic DNA was obtained from 303 consecutive systemic lupus erythematosus patients and 300 healthy blood donors from the southeastern region of Brazil. The polymorphic region of the FCGR3B gene was sequenced and the alleles FCGR3B*01, FCGR3B*02 and FCGR3B*03 were analyzed. RESULTS: The FCGR3B*01 allele was more frequent in systemic lupus erythematosus patients (43.1%) while the FCGR3B*02 allele prevailed among controls (63.7%) (P = 0.001). The FCGR3B*03 allele was found equally in both groups. The FCGR3B*01/*01 (20.7%) and FCGR3B*01/*02 (41.1%) genotypes were more frequent among systemic lupus erythematosus patients (P = 0.028 and P = 0.012, respectively) while the FCGR3B*02/*02 genotype was more frequent in controls (45.5%) (P < 0.001). One variant of the FCGR3B*01 allele previously described in Germany was found in only one control. A new variant of the FCGR3B*01 allele with two substitutions (A227G/G277A) was found in one control. Three variants of the FCGR3B*02 allele previously described in African-Americans, Brazilians, Chinese and Japanese were found in ten 10 patients and two controls. In addition, several single nucleotide polymorphisms at non-polymorphic positions were identified in both patients and controls. CONCLUSION: Susceptibility to systemic lupus erythematosus was associated with the FCGR3B*01 allele, as well as with the FCGR3B*01/*01 and FCGR3B*01/*02 genotypes. No association was found between FCGR3B genotypes and clinical manifestations, disease severity or the presence of autoantibodies.

RAC3 more than a nuclear receptor coactivator: a key inhibitor of senescence that is downregulated in aging.

Receptor-associated coactivator 3 (RAC3) is a nuclear receptor coactivator usually overexpressed in tumors that exerts oncogenic functions in the cytoplasm and the nucleus. Although as part of its oncogenic actions it was previously identified as an inhibitor of apoptosis and autophagy, its expression is required in order to preserve the pluripotency and embryonic stem cell self-renewal. In this work we investigated its role in cellular senescence. We found that RAC3 overexpression in the nontumoral HEK293 cells inhibits the premature senescence induced by hydrogen peroxide or rapamycin. The mechanism involves not only the inhibition of autophagy early induced by these stimuli in the pathway to senescence, but also the increase in levels and nuclear localization of both the cell cycle suppressors p53/p21 and the longevity promoters FOXO1A, FOXO3A and SIRT1. Furthermore, we found that RAC3 overexpression is required in order to maintain the telomerase activity. In tumoral HeLa cells its activity was inhibited by depletion of RAC3 inducing replicative senescence. Moreover, we demonstrated that in vivo, levels of RAC3 are downregulated in the liver from aged as compared with young rats, whereas the levels of p21 are increased, correlating with the expected senescent cell contents in aged tissues. A similar downregulation of RAC3 was observed in the premature and replicative senescence of human fetal WI-38 cells and premature senescence of hepatocyte HepG2 cell line. Taken together, all these results demonstrate that RAC3 is an inhibitor of senescence whose downregulation in aged individuals could be probably a tumor suppressor mechanism, avoiding the clonal expansion of risky old cells having damaged DNA.

[Extraskeletal primary osteosarcoma of the frontal region]. / Osteossarcoma extra-esquelético primário da região frontal.

BACKGROUND: Extraskeletal osteosarcoma (ESOS) in the head as a primary site has seldom been reported and none in the frontal region. METHODS: A 78-year-old Italian man presented with one month history of a frontal soft tissue mass. A CT scan showed a mass of uneven density occupying the subcutaneous soft tissue and involving fascial planes. No primary bone tumor was found. The entire mass was excised. The mass was solid measuring 0.8 x 0.6 x 0.5 cm. Extraskeletal osteoblastic osteosarcoma was diagnosed by light microscopy. The tumor recurred four months after the diagnosis. The tumor was again ressected. The patient was also submitted to low penetration radiation therapy. Nine months after the first biopsy the patient had symptoms due to infiltration to the base of the cranium. He died 10 months after the first biopsy. CONCLUSIONS: The first case with ESOS of the frontal region without a pre-existing condition or a history of irradiation is described.

Osteossarcoma extra-esquelético primário da regiäo frontal / Extraskeletal primary osteosarcoma of the frontal region

Objetivo. Osteossarcoma extra-esquelético (OSEE) primário de partes moles da cabeça é raro e näo há, ao que nos parece, relato dele originando na regiäo frontal. Métodos. Homem de 78 anos, italiano, com história de tumoraçäo em partes moles de regiao frontal há um mês. Tomografia computadorizada mostrou massa de densidade irregular ocupando tecido celular subcutâneo e fáscia. Nenhum tumor ósseo foi encontrado. A tumoraçäo foi completamente ressecada, media 0,8x0,6x0,5cm, e a superfície de corte era sólida. Diagnosticou-se osteossarcoma osteoblástico extra-esquelético. A neoplasia recorreu quatro meses após o diagnóstico e foi novamente ressecado. O paciente foi submetido também a radioterapia de baixa penetraçao, e nove meses depois da primeira biópsia tinha sintomas em decorrência da infiltraçäo neoplásica na base do crânio. O óbito ocorreu dez meses após a primeira biópsia. Conclusäo. Os autores descrevem o primeiro caso de OSEE da regiäo frontal sem uma condiçäo preexistente ou história de irradiaçäo.

Trigeminal somatosensory evoked potentials: a normal value study.

Normal somatosensory evoked potentials were obtained from the lower lip of 40 volunteers. Efforts were made to exclude artefact. A consistent triphasic wave form of three peaks and troughs was defined. There were greater variations in amplitude than latency between subjects. Statistically, one side of the lower lip can be used as a control for the contralateral side, but it may not be possible to have reliable normal values between subjects. Somatosensory evoked potentials may however represent an objective method of evaluating trigeminal sensory nerve function.