Reduced expression of AP27 protein, the product of a growth factor-repressible gene, is associated with diminished adipocyte differentiation.

We have recently characterized an adipocyte cDNA (clone 5) that is enhanced in expression by environmental and hormonal conditions favoring adipogenic differentiation. Moreover, certain agents including fibroblast growth factor and phorbol 12-myristate 13-acetate (but not epidermal growth factor) markedly inhibit clone 5 gene expression and prevent TA1 cell differentiation. These results led us to propose that a threshold level of the clone 5 gene product (AP27 protein) is required for triggering adipocyte differentiation. We have constructed vectors that direct the synthesis of clone 5 antisense RNA to reduce the levels of AP27 in adipogenic cell lines TA1 and 3T3-L1. We show here that when these cells express clone 5 antisense RNA, they fail to undergo morphological differentiation, whereas adipogenesis is unaffected in cells expressing antisense beta-actin or ferritin heavy-chain RNA. We further show that cells expressing clone 5 antisense RNA (but not the other antisense RNAs) are unable to induce the expression of characteristic "adipocyte-specific" mRNAs. The level of inhibition of differentiation by clone 5 antisense RNA correlates with decreased levels of AP27 protein. These results provide strong evidence that expression of AP27 is linked to adipogenic differentiation and that AP27 may be a component of an as-yet-uncharacterized signal-transduction pathway required for the triggering of adipocyte differentiation.     

Distribution of the serotonin 2C (5HT2C) receptor gene -759C/T polymorphism in patients with schizophrenia and normal controls

BACKGROUND: In patients with schizophrenia, the percentage of patients with diabetes has been found to be twice that of the normal population. The risk factors for this higher rate are unknown, although dietary, lifestyle, and genetic factors have all been suggested. Recently, a polymorphism (-759C/T) in the serotonin 2C (5HT2C) receptor promoter region has been associated with the development of diabetes in a normal control population, with the frequency of the T allele being higher in subjects without diabetes. AIM: To determine whether the distribution of the -759C/T polymorphism of the 5HT2C receptor is different among patients with schizophrenia and normal controls. METHODS: DNA from 100 patients with schizophrenia and 81 normal controls were analyzed for the 5HT2C receptor -759C/T polymorphism to determine its allelic frequencies in these two groups. RESULTS: Using a chi-squared analysis, no statistical differences in the distribution of C alleles and T alleles were found between the two groups (P=0.2931). CONCLUSIONS: Patients with schizophrenia have a higher risk for developing diabetes than the general population. We did not find a higher distribution of the -759T allele of the 5HT2C receptor in normal controls compared with in patients with schizophrenia. This suggests the higher prevalence of diabetes in schizophrenia is not due to this polymorphism.     

Further evidence for a strong genetic influence on the development of autoimmune thyroid disease: the California twin study.

To determine the heritable component of Graves' disease (GD) more precisely, a disease survey questionnaire completed by 13,726 California-born twin pairs over the age of 37 years was used as the foundation of this study. On the basis of this survey, each member of pairs reporting a past diagnosis of GD was then sought for an extensive telephone interview to seek diagnostic confirmation. Successful diagnostic evaluation occurred in 108 cases, of which 99 affected twin pairs form the basis of this report. The results indicate that the estimated pairwise concordance for is 17% in monozygotic (MZ) twins, and 1.9% in dizygotic (DZ) twins, which are in close agreement with a recent report from a Danish twin population. Moreover, the reported 3.9% occurrence of GD found in the first-degree relatives of affected twin pairs supports these findings. In contrast, only 0.45% of all twins, 0.27% of the spouses of twins, and approximately 0.16% of the first-degree relatives of unaffected twins were reported to have GD. Additionally, among the unaffected MZ twins of patients with GD, 17% reported having chronic thyroiditis and 10% other nonthyroid autoimmune conditions such as lupus erythematosus, pernicious anemia, or idiopathic thrombocytopenic purpura. Thus, a genetic predisposition appears to be shared for both thyroid and some nonthyroid autoimmune diseases. While it seems that GD is a strongly and nonspecifically heritable condition, the relatively low level of twin concordance indicates that this disease likely requires a nonheritable etiologic determinant(s) as well.     

Early experience with retrievable inferior vena cava filters in high-risk trauma patients

BACKGROUND: This study describes the use of retrievable IVC filters in a select group of trauma patients at high risk for deep vein thrombosis (DVT) and pulmonary embolism (PE). STUDY DESIGN: Retrievable IVC filters were placed in selected trauma patients who met high-risk criteria for deep vein thrombosis and PE according to institutional clinical management guidelines. All filters were placed percutaneously in the interventional radiology suite. Indications for filter placement were based on injury complex, weight-bearing status, and contraindications to enoxaparin or pneumatic compression devices. IVC filters were either removed or maintained. RESULTS: Retrievable IVC filters were placed in 35 patients after blunt trauma. Twenty-six patients (74%) sustained at least one orthopaedic injury; 17 patients (49%) were diagnosed with a pelvis fracture. Activity was limited to bed rest or spinal precautions in 18 patients (51%). Enoxaparin was contraindicated in 32 patients (91%) and injuries precluded the use of pneumatic compression devices in 11 (31%). IVC filters were removed in 18 patients (51%), with no reported complications. Patients with orthopaedic injuries and pelvis fractures were less likely to have their filters maintained (p = 0.040). CONCLUSIONS: Retrievable IVC filters offer a versatile option for prophylaxis in trauma patients at high risk for PE. Filter retrieval potentially spares the longterm complications of permanent filters in younger trauma patients. Retrievable filters warrant consideration in patients who meet high-risk criteria for deep vein thrombosis or PE who cannot receive effective mechanical prophylaxis and in whom contraindications to anticoagulation are expected to be temporary.