Overexpression of Frat1 in transgenic mice leads to glomerulosclerosis and nephrotic syndrome, and provides direct evidence for the involvement of Frat1 in lymphoma progression

The proto-oncogene Frat1 was originally identified as a common site of proviral insertion in transplanted tumors of Moloney murine leukemia virus (M-MuLV)-infected Emu-Pim1 transgenic mice. Contrary to most common insertion sites implicated in mouse T cell lymphomagenesis, retroviral insertional mutagenesis of Frat1 constitutes a relatively late event in M-MuLV-induced tumor development, suggesting that proviral activation of Frat1 contributes to progression of T cell lymphomas rather than their genesis. To substantiate this notion we have generated transgenic mice that overexpress Frat1 in various organs, including lymphoid tissues. Frat1 transgenic mice develop focal glomerulosclerosis and a nephrotic syndrome, but they do not exhibit an increased incidence of spontaneous lymphomas. Conversely, these mice are highly susceptible to M-MuLV-induced lymphomagenesis, and Frat1/Pim1 bitransgenic animals develop lymphomas with increased frequency compared to Pim1 transgenic littermates. These data support a role for Frat1 in tumor progression.     

Subcellular Phototoxicity of Photofrin-II and Lutetium Texaphyrin in Cells In Vitro

. Three cell types including bovine pulmonary artery endothelium cells (CPAE), rat kangaroo kidney cells (PTK₂), and human larynx epidermoid carcinoma cells (Hep-2) were used to study subcellular localisation and phototoxicity of Photofrin-II and lutetium texaphyrin (Lu Tex). Cells were examined for fluorescence after administration of the photosensitisers. Subcellular regions were exposed with a laser microbeam system that used an argon ion laser pumped dye laser generating a 630 nm for Photofrin-II and 730 nm for Lu Tex. Fluorescence detection suggests that the Photofrin-II is bound primarily to the mitochondria with some diffuse fluorescence in the rest of the cytoplasm. The fluorescence in Lu Tex treated cells appears to be localised to the lysosomes. The percentage of damaged cells following light exposure to the different subcellular regions after Photofrin-II or Lu Tex treatment demonstrates that the nuclear region was the most sensitive target followed by the perinuclear region and peripheral cytoplasm region. Paper received 27 January 1998; accepted after revision 21 August 1998.     

Unimpinged and impinged anterior cruciate ligament grafts: MR signal intensity measurements

Regionalized magnetic resonance (MR) signal intensities were quantitatively measured in impinged and unimpinged anterior cruciate ligament (ACL) grafts. Images were obtained with a 1.5-T imager, and signal intensity was measured in the proximal, middle, and distal thirds of the graft. In 15 unimpinged ACL grafts, the signal intensity remained low and did not vary during the 1st year of graft implantation (45 images). In contrast, 17 impinged ACL grafts showed an increase in signal intensity in the distal two-thirds of the graft that persisted 1-3 years after implantation (P less than .001). Unimpinged grafts were placed in tibial tunnels posterior and parallel to the slope of the intercondylar roof. Reconstructions with anterior tibial tunnels resulted in graft impingement that caused increases in graft signal intensity. This increase demonstrates a clear association between surgical technique and the subsequent MR appearance of the graft.     

Assessment of antiarrhythmic drug efficacy in the treatment of supraventricular arrhythmias

Few guidelines exist for judging the efficacy of antiarrhythmic drugs in patients with supraventricular arrhythmias. Useful definitions concerning the frequency and duration of supraventricular arrhythmias are offered, and complete and partial efficacy criteria are outlined for noninvasive electrocardiographic and invasive electrophysiologic techniques. Several open label, double-blind, parallel and crossover study designs are suggested for efficacy studies concerning the termination and prevention of supraventricular tachycardia. These recommendations are useful for designing new drug trials needed to evaluate properly the efficacy of antiarrhythmic agents in the treatment of various supraventricular arrhythmias.