Insulation lead failure: is it a matter of insulation coating, venous approach, or both?

Gag gene mutants of human immunodeficiency virus type 1 (HIV-1) were analyzed for their potentials of inhibiting the replication of wild-type (wt) HIV-2, the second AIDS virus, in a single-round of viral replication. Of twenty-two HIV-1 gag mutants examined, seven were found to efficiently interfere with the replication of wt HIV-2. Some mutants, which can suppress the replication of wt HIV-1, did not show this inhibitory effect. These mutants were defective at the late phase of viral replication. A mutant designated NL-C1a was demonstrated to be very effective against the replication of HIV-1 and HIV-2 in monocytic cells as well as in lymphocytic cells.     

Thioether adducts of a new imine reactive intermediate of the pneumotoxin 3-methylindole

Cytochrome P450 enzymes can potentially oxygenate 3-methylindole to form 2,3-epoxy-3-methylindoline which could rearrange to the stable metabolite 3-methyloxindole or open to form 3-hydroxy-3-methylindolenine, a putative electrophilic imine. The purpose of the current work was to determine if the imine was formed, and to characterize it via its adducts with thiol nucleophiles. Thiols were added to incubations of goat lung microsomes with 3-methylindole and deuterated analogues of 3-methylindole to trap the imine intermediate as its thioether conjugates. The N-acetylcysteine conjugate of 3-hydroxy-3-methylindolenine was detectable by LC/MS, but a molecular ion was not observed because the adduct rapidly dehydrated to form the 2-substituted indole. However, the imine was S-alkylated, and the intermediate carbinol was intramolecularly trapped using thioglycolic acid as a trapping agent that induced cyclocondensation to a lactone. The retention of one atom of deuterium from [2-2H]-3-methylindole and three from 3-[2H3-methyl]indole substantiated the mechanism in which the lactone adduct was produced by sulfur addition to either 3-hydroxy-3-methylindolenine or the epoxide. Tandem mass spectrometry of the lactone adduct produced a daughter ion spectrum consistent with this adduct. These studies demonstrated the existence of a new reactive intermediate of 3-methylindole, 3-hydroxy-3-methylindolenine, which may play a role in the pneumotoxicity of this chemical.     

Results of transplantation for acute and chronic hepatic allograft rejection

B-chronic lymphocytic leukemia (CLL) is characterized by an accumulation of long-lived, resting B cells expressing the Bcl-2 protein. However, less than 10% of the CLL patients shows bcl-2 gene rearrangement in blood cells, using traditional Southern blotting analysis. In the present study, rearrangement of the bcl-2 gene in CLL cells was studied by pulsed-field gel electrophoresis (PFGE). With this method, large DNA fragments (> 50-10,000 kb) could be analyzed. Blood CLL cells from 9 of 9 patients and 2 of 2 CLL cell lines showed rearranged bcl-2 gene. In comparison, healthy blood B cells and lymphoblastoid cell lines (LCLs) established from normal peripheral blood lymphocytes of the patients showed only germ line configuration. Thus, the possibility of restriction fragment length polymorphisms (RFLPs) in this gene could be excluded. The primary cell involved in CLL might be a progenitor B cell that has accidentally rearranged the bcl-2 gene. As a consequence, such cells express stable amount of Bcl-2 protein and do not enter apoptosis. During prolonged survival, such cells may acquire secondary changes including chromosomal translocations and mutations.     

Promises, hopes, and hyperbole: adoption of new informationtechnologies

Much of the talk about the information revolution so far is just that-talk. A provocative mix of promises, hopes and hyperbole, some of it will come true over time. Most of it will not. Technology is moving at ever-increasing speeds, and predictions about technology are accelerating even faster. Yet practical needs and wants rarely keep pace. The purpose of this paper is to explore the disparity between the promises and possibilities of the information revolution. It examines the factors that traditionally affect new technologies, and the role of end-users in affecting outcomes     

Electron-beam CT-angiography in abdominal aortic aneurysms. Initial results

PURPOSE: To evaluate the suitability of ultrafast electron-beam tomography (EBT) for the investigation of abdominal aortic aneurysms using CTA. METHODS: Thirty-one patients with suspected abdominal aortic aneurysm were investigated with EBT using an Evolution XP scanner (Siemens, Erlangen) with the newest software version 12.34 with continuous volume scanning of 140 images in 17 s. Collimation was 3 mm, table increment 4 mm with overlapping image reconstruction every 2 mm, exposure time 200 ms (124 mAs), resulting in a scan-range of 28 cm. A quantity of 80 ml contrast material was administered (flow 4 ml/s). Visualization of the abdominal aorta and its branches was performed with MIPs and shaded surface display. Evaluation of image quality was based on a four-step classification scale (1 = good, 4 = insufficient) for the demonstration of the abdominal aorta and the visceral, renal and iliac arteries. RESULTS: All EBT examinations demonstrated high and homogeneous density values along the whole vessel course with a mean density value of 258.7 +/- 47.3 HU for the abdominal aorta and the iliac arteries. Quality evaluation for the vessel demonstration showed mean values between 1.22 and 1.57 for the abdominal aorta and the visceral, renal and iliac arteries. CONCLUSIONS: EBT with 140 slices and slice reconstruction every 2 mm offers a high z-axis resolution resulting in high-quality CT angiographies of the whole abdominal aorta and its branches.     

Hemostatic and fibrinolytic indices in neonatal foals with presumed septicemia

Gerbils learned to approach a spatial-olfactory stimulus that signaled access to their pairmate. Experiments 1 and 3 used a discrimination procedure in which 1 conditioned stimulus (the CS+) was presented immediately before access to the pairmate and another (the CS-) was presented alone. Both male and female gerbils came to approach the CS+ sooner than the CS- and spent more time near the CS+ than the CS-. Discrimination learning was facilitated by making the CS+ and CS- spatially distinct (Experiment 3). Learning also was demonstrated in male gerbils, using a between-subjects design with a single CS. Pairing the CS with the opportunity for social interaction resulted in greater approach to the CS within 10 trials than presenting the CS and social opportunity in an unpaired fashion (Experiment 2). These findings demonstrate social-affiliative learning in the Mongolian gerbil. Similarities and differences between these findings and sexual conditioning effects in other species are discussed.     

Membrane topology of Borrelia burgdorferi and Treponema pallidum lipoproteins

A critical issue regarding the molecular architectures of Treponema pallidum and Borrelia burgdorferi, the agents of venereal syphilis and Lyme disease, respectively, concerns the membrane topologies of their major lipoprotein immunogens. A related question is whether these lipid-modified membrane proteins form intramembranous particles during freeze fracture electron microscopy. To address these issues, native borrelial and treponemal lipoproteins were reconstituted into liposomes of diverse composition. The importance of the covalently associated lipids for membrane association of lipoproteins was revealed by the observation that nonlipidated recombinant forms of both B. burgdorferi OspA and the T. pallidum 47-kDa immunogen (Tpp47) showed very weak or no binding to model bilayer vesicles. In contrast to control liposomes reconstituted with bacteriorhodopsin or bovine rhodopsin, two well-characterized transmembrane proteins, none of the lipoprotein-liposomes contained particles when examined by freeze fracture electron microscopy. To extend these findings to prokaryotic lipoproteins with relatively amphiphilic polypeptides, similar experiments were conducted with a recombinant nonlipidated form of Escherichia coli TraT, a lipoprotein which has putative transmembrane domains. The nonlipidated TraT oligomers bound vesicles derived from E. coli lipids but, surprisingly, did not form particles in the freeze-fractured liposomes. These findings support (i) a proposed topology of spirochetal lipoproteins in which the polypeptide is extrinsic to the membrane surface and (ii) the contention that particles visualized in freeze-fractured spirochetal membranes represent poorly characterized transmembrane proteins.     

Treatment outcome with radiation therapy after breast augmentation or reconstruction in patients with primary breast carcinoma

BACKGROUND: Analyses were performed to determine local control and cosmetic outcome of breast carcinoma patients with prosthetically augmented or reconstructed breasts who had received radiation therapy (RT). METHODS: Twenty-one newly diagnosed breast carcinoma patients with prosthetically augmented or reconstructed breasts were treated with external beam RT. All patients received whole breast RT (median dose, 50.4 gray [Gy]) and 19 were boosted to a median dose of 60.4 Gy. A median dose of 50.4 Gy was delivered to the regional lymph nodes in 12 patients. Tissue equivalent bolus material was used in six patients. Seventeen patients received adjuvant systemic therapy. Cosmetic results were evaluated at 3-6-month intervals. RESULTS: With a median follow-up of 32 months, good/excellent cosmetic results were observed in 71% of patients (100% in those with augmented breasts and 54% in those with reconstructed breasts). Four patients (19%) with fair/poor cosmetic outcomes required implant removal and/or revision. Multiple clinical and treatment-related factors were analyzed for their impact on cosmetic outcome. A worsened cosmetic result was observed with increasing stage (P = 0.076), breast reconstruction (vs. augmentation) (P = 0.030), and bolus application (P = 0.016). All patients with fair/poor cosmetic outcomes had time intervals from implant insertion to RT ranging from 53-213 days. Two patients developed an isolated local recurrence within the augmented breast. CONCLUSIONS: Patients with prosthetically augmented breasts can undergo RT and expect good/excellent cosmetic results. Patients with reconstructed breasts are at a significantly greater risk for cosmetic failure. This risk may be related to the higher percentage of patients with advanced disease, those who received bolus application, and those who received earlier delivery of RT (after the cosmetic procedure) in reconstructed breasts.