RESUMEN
We demonstrated the presence of an in vitro transmissible cytotoxic agent (TCA) in the cerebrospinal fluid (CSF) of patients with different acute neurological diseases. The nature of this agent is still a matter of study since repeated attempts have failed to identify it as a conventional infectious agent. Here, we describe the mechanisms through which TCA affects human astrocytes, demonstrating: a late apoptotic process, mediated by caspases 9 and 3 activation, involving the Bcl2-Bak-axis; an early and late p38 MAPK activation; an interference with the IL-8 and MCP-1 secretory response. These in vitro data provide initial evidence of TCA involvement as a pro-apoptotic and pro-inflammatory signal, directly affecting astrocytic behavior. The implications of these findings in certain neurological diseases will be discussed.
Asunto(s)
Apoptosis/efectos de los fármacos , Astrocitos/efectos de los fármacos , Citotoxinas/farmacología , Inflamación/inducido químicamente , Astrocitos/metabolismo , Línea Celular , Citotoxinas/metabolismo , Citometría de Flujo , HumanosRESUMEN
Neonatal Herpes simplex virus (HSV) pneumonia without apparent accompanying disseminated infection is a rare condition. We describe a case of neonatal pneumonia following maternal HSV type 1 viraemia in late pregnancy. A review of the literature shows that cases of HSV presenting as pneumonia in the first week of life are the most severe form of neonatal HSV.
Asunto(s)
Herpes Simple/diagnóstico , Herpesvirus Humano 1/aislamiento & purificación , Neumonía Viral/diagnóstico , Complicaciones Infecciosas del Embarazo/diagnóstico , Viremia/diagnóstico , Adulto , Resultado Fatal , Femenino , Humanos , Recién Nacido , EmbarazoRESUMEN
A transmissible cytotoxic agent thought to be associated with one or more misfolded protein(s) was found in several cerebrospinal fluid (CSF) samples from neurological patients. Since some experiments carried out to identify this unusual infectious factor showed the block of its propagation by rabbit gammaglobulins (IgGs), the search for such an activity by human IgGs was programmed. Neutralizing assays carried out using human sera as IgGs source showed a blocking property displayed by: twenty serum samples from as many patients with a diagnosis of acute infection, two of ten sera from healthy subjects and four serum samples from patients with lupus erythematous (SLE). When neutralizing sera were tested on cell cultures in immunofluorescence assays for the serum ability to label specific protein( s), similar fluorescent pictures resulted in treated and control cells. On the other hand, the SLE serum samples disclosed a granulosity of the nuclear material of cytotoxic cells in accordance with the DNA apoptotic laddering reported in previous papers. Oxidative disorders, as suggested by the immunoblotting analysis of the antioxidant enzymes Mn-superoxide dismutase (SOD2) and heme-oxygenase 1 (HO-1), point to an alteration of the oxidative pathway among the causes of the DNA damage induced by the cytotoxic transmissible agent under study.
Asunto(s)
Isquemia Encefálica/líquido cefalorraquídeo , Isquemia Encefálica/inmunología , Proteínas del Líquido Cefalorraquídeo/inmunología , Pruebas de Neutralización/métodos , Deficiencias en la Proteostasis/líquido cefalorraquídeo , Deficiencias en la Proteostasis/inmunología , Animales , Isquemia Encefálica/sangre , Células Cultivadas , Proteínas del Líquido Cefalorraquídeo/sangre , Proteínas del Líquido Cefalorraquídeo/líquido cefalorraquídeo , Citotoxinas/sangre , Citotoxinas/líquido cefalorraquídeo , Citotoxinas/inmunología , Fibroblastos/citología , Fibroblastos/inmunología , Hemo-Oxigenasa 1/sangre , Hemo-Oxigenasa 1/líquido cefalorraquídeo , Humanos , Inmunoglobulina G/farmacología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/líquido cefalorraquídeo , Lupus Eritematoso Sistémico/inmunología , Neuroglía/citología , Neuroglía/inmunología , Estrés Oxidativo/fisiología , Deficiencias en la Proteostasis/sangre , Conejos , Superóxido Dismutasa/sangre , Superóxido Dismutasa/líquido cefalorraquídeoRESUMEN
BACKGROUND: Cases of cytomegalovirus colitis are exceptionally reported in immuno-competent infant. The pathogenesis is uncertain but breast-feeding is considered as a main source of postnatal infection. CASE PRESENTATION: Here we report a full-term, formula-fed infant who developed a severe cytomegalovirus anaemia and colitis when aged 2 months. CONCLUSION: Even if the molecular identity between the cytomegalovirus-isolate of the infant and the maternal virus could not be demonstrated, we confirmed through laboratory investigation that cytomegalovirus infection was acquired postnatally. However, the source of cytomegalovirus infection remained unclear. Alternative modes of cytomegalovirus transmission are discussed.
Asunto(s)
Anemia/virología , Colitis/virología , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/transmisión , Citomegalovirus/aislamiento & purificación , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/virología , Diagnóstico Diferencial , Humanos , Lactante , Fórmulas Infantiles , Masculino , Nacimiento a TérminoRESUMEN
Positive results were attained when human peripheral blood lymphocytes (PBLs) were investigated for their ability to propagate a transmissible cytotoxic activity (TCA) isolated on VERO cell cultures from a sample of cerebrospinal fluid (CSF) drawn from a woman with ischemic brain injury. In consideration of this finding it can be assumed that "in vivo" blood lymphocytes contributed to give rise to the TCA detected "in vitro" in the CSF inoculum.
Asunto(s)
Citotoxinas/metabolismo , Linfocitos/metabolismo , Animales , Apoptosis , Técnicas de Cultivo de Célula , Líquido Cefalorraquídeo/citología , Chlorocebus aethiops , Pruebas Inmunológicas de Citotoxicidad , Citotoxinas/líquido cefalorraquídeo , Humanos , Linfocitos/sangre , Linfocitos/citología , Células VeroAsunto(s)
Anemia Aplásica/tratamiento farmacológico , Ciclosporina/efectos adversos , Infecciones por Virus de Epstein-Barr/etiología , Inmunosupresores/efectos adversos , Neumonía Viral/etiología , Viremia/etiología , Adulto , Anemia Aplásica/complicaciones , Suero Antilinfocítico/uso terapéutico , Ciclosporina/administración & dosificación , Ciclosporina/uso terapéutico , Herpesvirus Humano 4/fisiología , Humanos , Huésped Inmunocomprometido , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Masculino , Inducción de Remisión , Linfocitos T , Activación ViralRESUMEN
When inoculated into cell cultures to search for cytopathic viruses, six out of 384 cerebrospinal fluid (CSF) samples from patients with different neurological disorders proved to have a transmissible cytotoxic activity (TCA) not correlated to a conventional infectious agents. Properties shown by a TCA previously detected in the CSF sample of a patient with brain ischemia (Portolani et al., 2005) were shared by each of the newly isolated TCAs. We conclude that independently of the neurological clinical picture shown by the patient, the TCA detected in the CSF samples under study could have the same origin.
Asunto(s)
Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/virología , Adolescente , Adulto , Anciano , Animales , Isquemia Encefálica/líquido cefalorraquídeo , Chlorocebus aethiops , Efecto Citopatogénico Viral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pliegue de Proteína , Células VeroRESUMEN
We investigated a transmissible cytotoxicity isolated in VERO cell cultures from a sample of cerebrospinal fluid (CSF) drawn from a woman with ischemic brain injury. Amorphous aggregates formed by subunities of approximately 11 nm of diameter were detected in ultracentrifugates from partially purified cytotoxic cell preparations in the absence of virion-like particles which might justify the trasmissibility of this cytotoxic activity. Results of chemico-physical studies provided indications on the presence in the CSF of two protease-resistant acidic glycoproteins of about 39 and 27 kDa, respectively. The conformational change of a proteinic molecule may associate with particular properties such as tendency to aggregation, resistance to proteolysis, cytotoxicity. Considering that these same properties are shared by proteins present in the CSF sample under study, a hypothesis to pursue is that the CSF inoculum we isolated contained misfolded proteins formed in vivo following the ischemic injury of brain tissue. As far as the in vitro transmissibility of the cytotoxic activity, this could take place following the reproduction of the alterations of those proteins, independently of the original cause(s) which have fostered their formation in vivo.