Within-Host Models of High and Low Pathogenic Influenza Virus Infections: The Role of Macrophages

The World Health Organization identifies influenza as a major public health problem. While the strains commonly circulating in humans usually do not cause severe pathogenicity in healthy adults, some strains that have infected humans, such as H5N1, can cause high morbidity and mortality. Based on the severity of the disease, influenza viruses are sometimes categorized as either being highly pathogenic (HP) or having low pathogenicity (LP). The reasons why some strains are LP and others HP are not fully understood. While there are likely multiple mechanisms of interaction between the virus and the immune response that determine LP versus HP outcomes, we focus here on one component, namely macrophages (MP). There is some evidence that MP may both help fight the infection and become productively infected with HP influenza viruses. We developed mathematical models for influenza infections which explicitly included the dynamics and action of MP. We fit these models to viral load and macrophage count data from experimental infections of mice with LP and HP strains. Our results suggest that MP may not only help fight an influenza infection but may contribute to virus production in infections with HP viruses. We also explored the impact of combination therapies with antivirals and anti-inflammatory drugs on HP infections. Our study suggests a possible mechanism of MP in determining HP versus LP outcomes, and how different interventions might affect infection dynamics.     

L’electromyographie du penis: Une nouvelle exploration du muscle lisse caverneux et de son controle neurologique?

The authors have investigated the electrical activity of corpus cavernous, first according to Wagner and Gerstenberg’ method, then, since one year, according to Stief method, in the basal state and following intracavernosal injection of vasoactive agents, or following various stimulation tests. They have found again the electrical activity described by these authors, but have been confronted with the difficulty in quantifying the data. Specially single potential analysis seems to them little reliable and reproducible for an objective interpretation. At this stage of their experience, they test two simpler criteria interpretation: the richness of the electrical activity, and the reactivity of the recording to various stimulations. Their preminary results suggest a correlation between those criteria and the state of the autonomic nervous system of the penis.     

Complete sequences of the rRNA genes of Drosophila melanogaster

In this, the first of three papers, we present the sequence of the ribosomal RNA (rRNA) genes of Drosophila melanogaster. The gene regions of D. melanogaster rDNA encode four individual rRNAs: 18S (1,995 nt), 5.8S (123 nt), 2S (30 nt), and 28S (3,945 nt). The ribosomal DNA (rDNA) repeat of D. melanogaster is AT rich (65.9% overall), with the spacers being particularly AT rich. Analysis of DNA simplicity reveals that, in contrast to the intergenic spacer (IGS) and the external transcribed spacer (ETS), most of the rRNA gene regions have been refractory to the action of slippage-like events, with the exception of the 28S rRNA gene expansion segments. It would seem that the 28S rRNA can accommodate the products of slippage-like events without loss of activity. In the following two papers we analyze the effects of sequence divergence on the evolution of (1) the 28S gene "expansion segments" and (2) the 28S and 18S rRNA secondary structures among eukaryotic species, respectively. Our detailed analyses reveal, in addition to unequal crossing-over, (1) the involvement of slippage and biased mutation in the evolution of the rDNA multigene family and (2) the molecular coevolution of both expansion segments and the nucleotides involved with compensatory changes required to maintain secondary structures of RNA.      

Echocardiographic assessment and percutaneous closure of multiple atrial septal defects

Percutaneous coronary intervention can be associated with distal embolization of thrombotic material causing myocardial necrosis and infarction. We discuss the role of intravascular imaging to guide the use of a distal protection device by describing the outcome of a young woman presenting with non-ST elevation myocardial infarction. Coronary angiography demonstrated an isolated minor stenosis in the proximal left anterior descending coronary artery with slight haziness beyond the lesion. Intravascular ultrasound confirmed an extensive thrombus overlying a bulky atherosclerotic plaque. A distal filter wire was therefore successfully used to reduce the risk of distal embolization. The use of intravascular ultrasound in patients presenting with acute coronary syndrome may reveal large thrombi that are difficult to image using conventional angiographic techniques. Intravascular ultrasound can therefore be used as a tool to select lesions requiring distal protection.     

Evidence suggesting that a cyclic AMP-dependent protein kinase is a positive regulator of proliferation in Cloudman S91 melanoma cells.

Wild-type Cloudman S91 melanoma cells have a retarded rate of division when agents which raise cyclic AMP levels such as melanotropin, protaglandin E1, or cholera toxin are supplemented to the culture medium. A mutant cell line was isolated which had the opposite response, i.e., the mutant grew very slowly unless agents which raised cyclic AMP levels were present (Pawelek et al., '75a). In this report evidence is presented indicating that the molecular basis for the mutant phenotype resides in the major cyclic AMP-dependent protein kinase found in the cells. The mutant kinase had increased thermolability and an elevated activation constant for cyclic AMP over the corresponding wild-type kinase. It is proposed that the elevated requirement for cyclic AMP for the proliferation of cAdep cells is related to the elevated activation constant of the kinase, suggesting that the kinase is a positive regulator of proliferation in Cloudman S91 cells.