Left ventricular apex visualization: the value of magnetic resonance imaging

We have previously shown that prolonged interferon-beta (IFN-beta) treatment of RS485 cells (NIH3T3 cells transformed with multiple copies of an LTR-cHa-ras oncogene) resulted in the phenotypic reversion of 1%-5% of the culture, depending on the conditions used. This reversion persisted after IFN-beta was discontinued, although the revertants retained the LTR-cHa-ras and continued to express ras mRNA and p21. Clones were prepared of such persistent revertant cell lines (PRs). Expression of lysyl oxidase (LOX), which appears to act as a suppressor of ras transformation, was downregulated in RS485 and upregulated in the PRs. When retinoic acid (RA) was combined with IFN-beta treatment of the RS485 cultures, a different mechanism of reversion predominated. Following 60 days of treatment with 20 IU/ml of IFN-beta and 10 microM RA, all of the multiple (3-5) copies of the transforming LTR-c-Ha-ras originally present in RS485 cells were deleted from the genome in 72% of 54 revertant cell lines isolated. As in the case of revertants observed after treatment with IFN-beta alone, LOX mRNA expression was upregulated in all of the revertants that resulted from the treatment with IFN plus RA. The level of LOX mRNA expression acts, therefore, as an indicator of transformation in this system.     

The state space extension method in the theory of absolutestability

This paper shows how the state space extension method can be used to derive frequency domain criteria for stability of systems with different kinds of uncertainties. The main result is illustrated by a number of examples     

Development of cooperative territoriality in juvenile lions

African lions, Panthera leo, engage in many cooperative activities including hunting, care of young, and group territoriality, but the contribution of juvenile lions to these activities has never been documented. Here we present experimental evidence that juvenile lionesses make a gradual transition to group-territorial defence between weaning (8 months) and sexual maturity (42 months). When challenged by simulated intruders played from a loud-speaker, juvenile females (but not males) become progressively more likely to join the adult females in territorial defence with age, and their behaviour is affected by both the number of defending adults and the number of intruders. We interpret the ability of juveniles to assess relative numbers as an adaptation for assessing the risk of territorial conflict according to their own fighting ability, and the ability of their pride of successfully defend the territory. The difference between the sexes reflects the greater value of the natal territory to philopatric females. Adult females display a variety of strategies when defending the territory, including unconditional and conditional forms of cooperation. We show here that individuals display the rudiments of these strategies as juveniles.     

Adenovirus-mediated gene transfer of inhibitors of apoptosis protein delays apoptosis in cerebellar granule neurons

The inhibitor of apoptosis (IAP) family of antiapoptotic genes, originally discovered in baculovirus, exists in animals ranging from insects to humans. Here, we investigated the ability of IAPs to suppress cell death in both a neuronal model of apoptosis and excitotoxicity. Cerebellar granule neurons undergo apoptosis when switched from 25 to 5 mM potassium, and excitotoxic cell death in response to glutamate. We examined the endogenous expression of four members of the IAP family, X chromosome-linked IAP (XIAP), rat IAP1 (RIAP1), RIAP2, and neuronal apoptosis inhibitory protein (NAIP), by semiquantitative reverse PCR and immunoblot analysis in cultured cerebellar granule neurons. Cerebellar granule neurons express significant levels of RIAP2 mRNA and protein, but expression of RIAP1, NAIP, and XIAP was not detected. RIAP2 mRNA content and protein levels did not change when cells were switched from 25 to 5 mM potassium. To determine whether ectopic expression of IAP influenced neuronal survival after potassium withdrawal or glutamate exposure, we used recombinant adenoviral vectors to target XIAP, human IAP1 (HIAP1), HIAP2, and NAIP into cerebellar granule neurons. We demonstrate that forced expression of IAPs efficiently blocked potassium withdrawal-induced N-acetyl-Asp-Glu-Val-Asp-specific caspase activity and reduced DNA fragmentation. However, neurons were only protected from apoptosis up to 24 h after potassium withdrawal, but not at later time points, suggesting that IAPs delay but do not block apoptosis in cerebellar granule neurons. In contrast, treatment with 100 microM or 1 mM glutamate did not induce caspase activity and adenoviral-mediated expression of IAPs had no influence on subsequent excitotoxic cell death.     

Molecular fine-specificity analysis of antibody responses to human cytomegalovirus and design of novel synthetic-peptide-based serodiagnostic assays

BACKGROUND: Glomerular monocyte infiltration is an early feature of lipid-mediated renal injury in animal models. Interactions between mesangial and infiltrating mononuclear cells may contribute to the development of glomerular scarring. METHODS: Adherence of U-937 monocytes to low-density lipoprotein (LDL)- or tumor necrosis factor alpha (TNFalpha)-prestimulated human mesangial cells was assessed by colorimetry of nuclear staining with crystal violet. Blocking antibodies were added to examine the mechanisms of binding. Adhesion molecule expression and fibronectin synthesis were measured by ELISA. RESULTS: Preincubation of mesangial cells for 24 hours with LDL (100 micrograms/ml) or mildly oxidized (minimally modified) LDL (MM-LDL) increased monocyte adhesion by 207% and 240%, respectively, compared with control nonstimulated cells (100%). TNFalpha (100 U/ml) enhanced binding by 335% and up-regulated intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression by 505% and 179%, respectively, as compared with MM-LDL (120% and 116%) and LDL, which had no effect. Blocking antibodies to these adhesion molecules inhibited monocyte binding to TNFalpha- and, to a lesser extent, MM-LDL-primed mesangial cells, but had no effect after LDL pretreatment. In contrast to TNFalpha, MM-LDL and LDL increased mesangial cell-associated fibronectin, whereas antibodies to fibronectin inhibited monocyte binding to lipoprotein-stimulated but not TNFalpha-stimulated cells. CONCLUSIONS: Although enhanced monocyte adhesion to TNFalpha- and, to a lesser extent, MM-LDL-stimulated mesangial cells is mediated by changes in ICAM-1 and VCAM-1 expression, both LDL and MM-LDL promote similar cellular interactions as a result of increased fibronectin production.