Parada cardíaca: presentación mortal de una miocarditis viral / Cardiac arrest: Fatal presentation of viral myocarditis

La miocarditis es un trastorno inflamatorio del miocardio que cursa con la necrosis de los miocitos. La principal causa son las infecciones virales. La presentación clínica es muy variada: desde formas leves hasta formas fulminantes que cursan con la muerte y que se inician frecuentemente con síntomas banales. Presentamos el caso de un niño de 18 meses que acude a urgencias por astenia y anorexia de 24h de evolución, con antecedente de fiebre en el contexto de infección respiratoria de vías altas la semana anterior. A su llegada a urgencias y durante las primeras horas de observación la exploración física fue rigurosamente normal. Posteriormente presentó empeoramiento progresivo del estado general (palidez y mala perfusión periférica) con alteraciones analíticas (acidosis metabólica, insuficiencia renal e hiperglucemia) y de forma brusca parada cardiorrespiratoria sin respuesta a maniobras de reanimación cardiopulmonar (AU)

Myocarditis is an inflammatory disease of the myocardium accompanied by necrosis of myocytes. The main causes are viral infections. The clinical presentation varies from mild forms to devastating ones which usually begin with trivial symptoms with progression, in some cases, to death. We report the case of an 18 month-old male toddler consulting for asthenia and anorexia for the last 24h and a previous history of respiratory tract infection with high fever in the last week. Upon arrival at the emergency room and during the first hours of admission, physical examination was perfectly normal. Later, his general state gradually deteriorated, with biochemical disturbances (metabolic acidosis, renal failure and hyperglycaemia) and, eventually, a sudden cardiac arrest, with no response to cardiopulmonary resuscitation manoeuvres (AU)

[Cardiac arrest: fatal presentation of viral myocarditis]. / Parada cardíaca: presentación mortal de una miocarditis viral.

Myocarditis is an inflammatory disease of the myocardium accompanied by necrosis of myocytes. The main causes are viral infections. The clinical presentation varies from mild forms to devastating ones which usually begin with trivial symptoms with progression, in some cases, to death. We report the case of an 18 month-old male toddler consulting for asthenia and anorexia for the last 24h and a previous history of respiratory tract infection with high fever in the last week. Upon arrival at the emergency room and during the first hours of admission, physical examination was perfectly normal. Later, his general state gradually deteriorated,with biochemical disturbances (metabolic acidosis, renal failure and hyperglycaemia) and, eventually, a sudden cardiac arrest, with no response to cardiopulmonary resuscitation manoeuvres.

IL-3 es incapaz de rescatar células scid dependientes de IL-3 tras su exposición a irradiación por rayos X / IL-3 is unable to rescue IL-3-dependent scid cells after exposure to X-ray irradiation

Los factores de crecimiento pueden rescatar de la apoptosis a las células tras sufrir daños en su DNA, al regular diferentes mecanismos de reparación del DNA. En este trabajo hemos investigado el efecto radio-protector de la IL-3 en procesos de reparación de roturas de doble cadena del DNA, utilizando modelos celulares de cultivos primarios o una línea celular establecida, la CIT.1, derivada de medula ósea de ratones con inmunodeficiencia severa combinada (scid). Los ratones scid carecen de linfocitos T y B maduros debido a una mutación de la subunidad catalítica de la proteína DNA-PK, directamente implicada en la reparación de las roturas de doble cadenas producidas durante la recombinación V(D)J. Nuestros datos demuestran que la IL-3 es capaz de rescatar células Ba/F3, dependientes de este factor de proliferación, irradiadas con rayos X, pero no células de cultivos primarios o de la línea CIT.1, también dependientes de IL-3 y derivadas de ratones scid. La irradiación con rayos X reduce la actividad clonogénica de células derivadas de ratones scid, en contraposición con ratones normales, donde la IL-3 mantiene la clonogenicidad tras la irradiación. Sin embargo, utilizando bleomicina, droga radiomimética, la IL-3 fue capaz de rescatar tanto células derivadas de ratones normales como de ratones scid. La diferencia entra la capacidad de la IL-3 de rescatar células irradiadas o tratadas con bleomicina esta probablemente asociada a los diferentes mecanismos de inducción de daño utilizados por cada agente. Estos resultados implican a la DNA-PK en los procesos de radio-protección de la IL-3 tras irradiación y rotura de la doble cadena de DNA (AU)

Involvement of p53 and interleukin 3 in the up-regulation of CD95 (APO-1/Fas) by X-ray irradiation.

Interleukin 3-dependent bone marrow and Ba/F3 cells present constitutive Fas expression. A dose dependent increase in Fas surface expression was induced in these cells by X-ray irradiation. Using primary cell cultures and established cell lines derived from p53-null mice (p53-/-), we demonstrated that the increase in Fas expression upon X-ray irradiation is dependent on the presence of at least one wild-type p53 allele. Fas induction by X-ray irradiation was negatively modulated by IL-3; an earlier Fas induction was observed in the absence of IL-3 or at low IL-3 concentrations. However, IL-3 withdrawal in non-irradiated cells did not induce an increase in Fas expression. X-ray irradiation of Ba/F3 cells induced the expression of functional Fas receptors. Therefore, in IL-3-dependent cells, IL-3 regulates the rate of Fas expression, which is correlated with the degree of apoptosis observed in X-irradiated cells. Finally, we demonstrate that IL-3 controls the degree of Fas expression induced by irradiation through a p53-mediated pathway.

The role of p53 in death of IL-3-dependent cells in response to cytotoxic drugs.

This report examines the cytotoxicity of chemotherapeutic agents to primary bone marrow-derived IL-3-dependent cells. Such cells derived from p53-null mice were resistant to almost 100-fold higher concentrations of the inhibitors of deoxyribonucleotide synthesis FUdR, methotrexate and hydroxyurea than cells with wild-type p53. In contrast, the cytotoxicity of the DNA damaging agents X-irradiation, cisplatin or bleomycin was p53-independent. The topoisomerase II inhibitor etoposide induced p53-dependent death, which suggests that DNA damage may not be its primary mechanism of cytotoxicity in this cell type. An IL-3-dependent cell line which expresses wild-type p53 was used to demonstrate that the ability of cytotoxic drugs to increase p53 expression level does not control their ability to induce p53-dependent loss of clonigenicity. Finally, comparison with a p53-null IL-3-dependent cell line was used to show that absence of p53 delays the rate of entry into apoptosis following treatment with either DNA damaging agents or inhibitors of deoxyribonucleotide synthesis. This distinguishes short-term effects of p53 on rate of entry into apoptosis from its role in controlling ultimate cell survival. Oncogene (2000) 19, 3556 - 3559

Ligation of CD53/OX44, a tetraspan antigen, induces homotypic adhesion mediated by specific cell-cell interactions.

The CD53 antigen is a member of the tetraspan family of proteins with unknown function. Stimulation of rat IR938F B-cell lymphoma cells with monoclonal antibody MRC OX44 (anti-rat CD53) triggered a homotypic adhesion reaction which reached a maximum effect at 24 hr. This effect occurred at 37 degrees C but not at 4 degrees C. Adhesion was prevented by removal of divalent cations, Ca2+ and Mg2+, with EGTA and EDTA as chelating agents. The adhesion induced by MRC OX44 was inhibited by cycloheximide and actinomycin D, suggesting that de novo protein synthesis was required for this effect. The addition of mAb WT1 against rat LFA-1 (CD11a) antigen had no effect on adhesion, suggesting that the cell-cell interaction is not mediated by the expression of LFA-1 antigen. The intracellular signals required to induce adhesion were inhibited by two tyrosine kinase inhibitors, genistein and piceatannol. Wortmannin, a selective inhibitor of phosphoinositide 3-kinase activity, completely blocked adhesion. Two protein kinase C inhibitors, H7 and bisindolylmaleimide, inhibited the adhesion, suggesting that part of the signal is mediated by PKC. Electron microscopy of aggregated cells showed that the interaction is localized to short membrane regions, where contact areas of higher density in opposing zones from both cells were detected. We postulate that there is a common adhesion mechanism that is modulated by several tetraspan family members and associated proteins. This adhesion structure might represent a novel form of cell communication among lymphoid cells.