Mutual exclusion between related phages

The discovery of the breakdown of superinfecting phage needs to be supplemented by genetic tests to find out whether the phage whose nucleic acid is broken down is, indeed, unable to contribute genetic markers to the progeny. The present paper presents experiments of this kind, whose results leave no doubt that the breakdown of superinfecting phage is strictly paralleled by exclusion from the progeny of the genetic markers it contains. We are presenting also some experiments in which the stimulating phage alone or both the stimulating and the superinfecting phage have been inactivated by irradiation with ultraviolet light. These experiments serve to characterize functions which have remained unimpaired in ultraviolet treated phage and their relation to multiplicity reactivation of ultraviolet treated phage

Plaque formation and isolation of pure lines with poliomyelitis virus

Plaques have been produced with the three types of poliomyelitis viruses on monolayer tissue cultures of monkey kidney and monkey testis. The number of plaques was proportional to the concentration of the virus. Each plaque originates, therefore, from a single virus particle, defined as the virus unit that is unseparable by dilution. The plaques are due to the specific action of the virus since they are suppressed by type-specific antiserum. Pure virus lines were established by isolating the virus population produced in single plaques. These derived virus lines had the same morphological, serological, and pathogenic properties as the parent strain. High titer virus stocks, with titers up to 7 x 10^8 plaque-forming particles per ml., were obtained

ONE-STEP GROWTH CURVE OF WESTERN EQUINE ENCEPHALOMYELITIS VIRUS ON CHICKEN EMBRYO CELLS GROWN IN VITRO AND ANALYSIS OF VIRUS YIELDS FROM SINGLE CELLS

The rate of adsorption of WEE virus onto chicken embryo cells in vitro was determined both on a cell layer and on a cell suspension. One-step growth curves were determined in cell suspensions and on cell layers. The latent period varied between 2 and 3½ hours; it was shorter on cell layers and decreased with higher multiplicity of infection. The shortest period is probably the real latent period. The growth curves of the virus showed an initial exponential rise and reached a maximal constant value after 6 to 8 hours. The maximum virus yield per cell varied between 200 and 1000 on the cell layer, and between 100 and 200 in suspended cells. The yield of single infected cells was determined. An analysis of the distributions of the individual yields obtained after various periods of virus growth led to two main conclusions: (1) that virus is released from the same cell over a long period of time; (2) that one phase of the intracellular virus growth is exponential

Augmentation of cytotoxic drug action and X-irradiation by antibodies.

The effect of an antiserum containing antibodies against cell surface components of PyBHK cells on the action of certain anticancer agents has been studied using a colony formation inhibition assay. The effects of x-rays, chlorambucil, CCNU and possibly ICRF 159 are augmented by the antiserum whereas methotrexate and vinblastine are not

Comparison of two surrogate estimates of insulin resistance to predict cardiovascular disease in apparently healthy individuals

Background and aims: Insulin resistance is associated with a cluster of abnormalities that increase cardiovascular disease (CVD). Several indices have been proposed to identify individuals who are insulin resistant, and thereby at increased CVD risk. The aim of this study was to compare the abilities of 3 indices to accomplish that goal: 1) plasma triglyceride × glucose index (TG × G); 2) plasma triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C); and 3) Metabolic Syndrome (MetS). Methods and results: In a population sample of 723 individuals (486 women and 237 men, 50 ± 16 and 51 ± 16 years old, respectively), baseline demographic and metabolic variables known to increase CVD risk and incident CVD were compared among individuals defined as high vs. low risk by: TG × G; TG/HDL-C; or MetS. CVD risk profiles appeared comparable in high risk subjects, irrespective of criteria. Crude incidence of CVD events was increased in high risk subjects: 12.2 vs. 5.3% subjects/10 years, p = 0.005 defined by TG/HDL-C; 13.4 vs. 5.3% subjects/10 years, p = 0.002 defined by TG × G; and 13.4% vs. 4.5% of subjects/10 years, p < 0.001 in subjects with the MetS. The area under the ROC curves to predict CVD were similar, 0.66 vs. 0.67 for TG/HDL-C and TG × G, respectively. However, when adjusted by age, sex and multiple covariates, hazard ratios for incident CVD were significantly increased in high risk patients classified by either TG/HDL-C ratio (2.18, p = 0.021) or MetS (1.93, p = 0.037), but not by TG × G index (1.72, p = 0.087). Conclusion: Although the 3 indices identify CVD risk comparably, the TG × G index seems somewhat less effective at predicting CVD.Facultad de Ciencias Médica

ROL DE LOS CITOCROMOS P450 (CLAN CYP4) DEL INTEGUMENTO DE Triatoma infestans EN LA RESISTENCIA A DELTAMETRINA

Triatoma infestans es el principal vector de la enfermedad de Chagas en el Cono Sur de Sudamérica. Su control se basa en el rociado con insecticidas piretroides (principalmente deltametrina); sin embargo, desde hace varios años se vienen detectando fallas de control debido al desarrollo de poblaciones resistentes. Dentro de los mecanismos más relevantes en el fenómeno de resistencia se destacan: una mayor capacidad de metabolizar el insecticida debido a un aumento en la expresión de genes relacionados con detoxificación (resistencia metabólica), mutaciones que alteran el sitio de acción (resistencia kdr), y un engrosamiento cuticular que provoca una disminución en la penetración del insecticida (factor cuticular).&nbsp; En nuestro laboratorio se ha demostrado por primera vez en insecto que existen diferencias significativas en la cantidad de hidrocarburos cuticulares en especímenes T. infestans resistentes a piretroides, junto con un grosor aumentado de la cutícula. Estas características se correlacionan con una penetración reducida del insecticida. &nbsp;Aunque es bien sabido que los procesos de detoxificación de xenobióticos ocurren principalmente en el cuerpo graso de los insectos, los insecticidas de contacto encuentran en el integumento (el tejido más externo de los insectos) la primera barrera y es en este tejido donde se produce la primera interacción. Las citocromo P450 monoxigenasas (P450) constituyen una de las mayores superfamilias de enzimas encontradas en la naturaleza, catalizando la conversión de compuestos lipofílicos (tanto endógenos como xenobióticos) en derivados más hidrofílicos. Debido a su gran abundancia, los genes P450 (CYP) se asignan en familias y subfamilias; también se utiliza una agrupación de mayor orden denominada clan, encontrándose 4 clanes en la naturaleza. Varias subfamilias del clan 3 y clan 4 en insectos hay sufrido expansiones génicas, resultando en "blooms" de P450 linaje específicos, que han sido asociados con resistencia a insecticidas. Como parte de mi plan de tesis,&nbsp; y a partir de la información disponible del transcriptoma de integumento de T. infestans, hemos comenzado con el estudio de los genes CYP de integumento. Hemos detectamos que la detoxificación de deltametrina comienza en el integumento de vinchucas resistentes, con potencial participación de P450 del clan 4. Dentro de los 15 genes estudiados, dos de ellos -CYP3093A11 y CYP4EM10- se encuentran constitutivamente sobreexpresados en el integumento (pero no en otros tejidos) de vinchucas resistentes. Cuando estos dos genes fueron silenciados específicamente mediante ARN de interferencia, otro gen del clan CYP4 resultó sobreexpresado en el integumento, posiblemente como respuesta al silenciamiento de los genes antes mencionados. Estos resultados permitieron tener una primera aproximación para comenzar a estudiar el rol de los citocromos P450 del integumento de T. infestans en la detoxificación de deltametrina. Esta información contribuye a la hipótesis de que hay múltiples mecanismos participando en el complejo fenómeno de resistencia a insecticidas. En este sentido, se demuestra que el tejido epidérmico contribuye no solo con la resistencia cuticular, sino también con una activa participación en la resistencia metabólica

Functional heartburn has more in common with functional dyspepsia than with non-erosive reflux disease

INTRODUCTION: Functional dyspepsia and non-erosive reflux disease (NERD) are prevalent gastrointestinal conditions with accumulating evidence regarding an overlap between the two. Still, patients with NERD represent a very heterogeneous group and limited data on dyspeptic symptoms in various subgroups of NERD are available. AIM: To evaluate the prevalence of dyspeptic symptoms in patients with NERD subclassified by using 24 h impedance-pH monitoring (MII-pH). METHODS: Patients with typical reflux symptoms and normal endoscopy underwent impedance-pH monitoring off proton pump inhibitor treatment. Oesophageal acid exposure time (AET), type of acid and non-acid reflux episodes, and symptom association probability (SAP) were calculated. A validated dyspepsia questionnaire was used to quantify dyspeptic symptoms prior to reflux monitoring. RESULTS: Of 200 patients with NERD (105 female; median age, 48 years), 81 (41%) had an abnormal oesophageal AET (NERD pH-POS), 65 (32%) had normal oesophageal AET and positive SAP for acid and/or non-acid reflux (hypersensitive oesophagus), and 54 (27%) had normal oesophageal AET and negative SAP (functional heartburn). Patients with functional heartburn had more frequent (p<0.01) postprandial fullness, bloating, early satiety and nausea compared to patients with NERD pH-POS and hypersensitive oesophagus. CONCLUSION: The increased prevalence of dyspeptic symptoms in patients with functional heartburn reinforces the concept that functional gastrointestinal disorders extend beyond the boundaries suggested by the anatomical location of symptoms. This should be regarded as a further argument to test patients with symptoms of gastro-oesophageal reflux disease in order to separate patients with functional heartburn from patients with NERD in whom symptoms are associated with gastro-oesophageal reflux

Separation of poliovirus and poliovirus RNA on Sephadex G 200

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41675/1/705_2005_Article_BF01241426.pd

Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell

Riesgo de enfermedades cardiovasculares según categorías de presión arterial en una cohorte argentina

SummaryBackground: Hypertension is a recognized strong risk factor for cardiovascular disease. However, no data was available in our country to quantify the relationship between blood pressure and cardiovascular event.Objective: to quantify the risk of cardiovascular events according to blood pressure categories.Methods: A prospective epidemiological study was conducted in 1526 inhabitants from Rauch City, (Buenos Aires, Argentina) between 1997 and 2012. Subjects were classified into one of these blood-pressure categories: 1-optimal, 2-normal, 3-high-normal, 4-grade 1 hypertension, 5-grade 2 hypertension and 6-grade 3 hypertension. The first CVD event, including unstable angina pectoris, fatal and non-fatal myocardial infarction, myocardial revascularization, and fatal or non-fatal stroke, was defined as the primary endpoint. Multivariable Cox proportional-hazards regression models were used to estimate the relative risk (HR) of CVD according to base-line blood-pressure categories.Results: In 2012, 1124 individuals (73.7% of the baseline sample), 719 women and 405 men (in 1997, aged 45±16 and 46±16 respectively) or their relatives in case of death, could be surveyed again in order to obtain information concerning incident CVD events. Cardiovascular event rates and  HR values increased in a stepwise manner across the blood pressure categories (p for trend across categories &lt;0.001 in both sex); however, in subjects aged ?55 years a j-curve phenomenon was observed, showing the lowest incidence in the high-normal category. In all categories CVD events rates were higher for men.Conclusion: This study quantified relationships between BP and CVD starting from high-normal blood pressure in Argentina.   Resumen Antecedentes: La hipertensión arterial es un reconocido factor de riesgo de enfermedad cardiovascular (ECV). Sin embargo, no hay información en Argentina que cuantifique la relación entre la presión arterial (PA) y ECV.Objetivo: Cuantificar el riesgo de ECV de acuerdo a categorías de PA.Método: Se realizó un estudio epidemiológico prospectivo en 1526 habitantes de la ciudad de Rauch (Buenos Aires, Argentina) entre octubre de 1997 y febrero de 2012. Los individuos fueron clasificados en las categorías de PA: 1-óptima, 2-normal, 3-normal-alta, 4-hipertensión grado 1, 5-hipertensión grado 2 y 6-hipertensión grado 3. Fue definido como punto final el primer evento de ECV (angina de pecho inestable, infarto fatal y no fatal, revascularización, y accidente cerebrovascular fatal y no fatal). El riesgo relativo (HR) de tener un evento fue estimado usando modelos de regresión multivariable de Cox.Resultados: En 2012, fueron re-encuestados 1124 individuos (73,7% de la muestra basal), 719 mujeres y 405 hombres, o sus parientes en caso de muerte (edad en 1997 45±16 y 46±16 años, respectivamente). Las tasas de ECV y los HR se incrementaron para cada categoría de PA por encima de la óptima (p &lt; 0.001 en ambos sexos); sin embargo, en sujetos mayores de 55 años se observó un fenómeno de curva en J, con la incidencia más baja en la categoría normal-alto. En todas las categorías la tasa de eventos fue mayor en hombres.Conclusión: Este estudio demostró y cuantificó la relación entre de PA y ECV a partir de PA normal alta en una población de Argentina. </p