Macrophage derived TNFα promotes hepatic reprogramming to Warburg-like metabolism.

During infection, hepatocytes must undergo a reprioritization of metabolism, termed metabolic reprogramming. Hepatic metabolic reprogramming in response to infection begins within hours of infection, suggesting a mechanism closely linked to pathogen recognition. Following injection with polyinosinic:polycytidylic acid, a mimic of viral infection, a robust hepatic innate immune response could be seen involving the TNFα pathway at 2 h.

Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy.

The use of adeno-associated virus (AAV) as a gene therapy vector has been approved recently for clinical use and has demonstrated efficacy in a growing number of clinical trials. However, the safety of AAV as a vector has been challenged by a single study that documented hepatocellular carcinoma (HCC) after AAV gene delivery in mice. Most studies have not noted genotoxicity following AAV-mediated gene delivery; therefore, the possibility that there is an association between AAV and HCC is controversial.

Species D adenoviruses as oncolytics against B-cell cancers.

Purpose: Oncolytic viruses are self-amplifying anticancer agents that make use of the natural ability of viruses to kill cells. Adenovirus serotype 5 (Ad5) has been extensively tested against solid cancers, but less so against B-cell cancers because these cells do not generally express the coxsackie and adenoviral receptor (CAR). To determine whether other adenoviruses might have better potency, we "mined" the adenovirus virome of 55 serotypes for viruses that could kill B-cell cancers.

Gene therapy in a murine model of methylmalonic acidemia using rAAV9-mediated gene delivery.

Methylmalonic acidemia (MMA), an inherited metabolic disorder caused by deficient activity of methylmalonyl-CoA mutase, carries a poor prognosis for long-term survival. While administration of a recombinant adeno-associated virus serotype 8 vector (rAAV8) can rescue Mut(-/-) mice from neonatal lethality and provide sustained phenotypic correction, translation of gene therapy to human subjects will likely require multiple rounds of systemic administration and, ideally, the use of a vector that transduces the kidney. To examine the effectiveness of alternative rAAVs in the treatment of MMA, a serotype 9 rAAV expressing the Mut cDNA was constructed and delivered to newborn Mut(-/-) mice (n=11).

Adeno-associated virus serotype 8 gene transfer rescues a neonatal lethal murine model of propionic acidemia.

Propionic acidemia (PA) is an autosomal recessive disorder of metabolism caused by a deficiency of propionyl-coenzyme A carboxylase (PCC). Despite optimal dietary and cofactor therapy, PA patients still suffer from lethal metabolic instability and experience multisystemic complications. A murine model of PA (Pcca(-/-)) of animals that uniformly die within the first 48 hr of life was used to determine the efficacy of adeno-associated viral (AAV) gene transfer as a potential therapy for PA.

Infection and killing of multiple myeloma by adenoviruses.

Oncolytic virotherapy makes use of the natural ability of viruses to infect and kill cancer cells. Adenovirus serotype 5 (Ad5) has been approved for use in humans as a therapy for solid cancers. In this study, we have tested whether Ad5 and low-seroprevalence adenoviruses can be used as oncolytics for multiple myeloma (MM).

Systemic delivery of therapeutic viruses.

The treatment of certain diseases will require the systemic delivery of therapeutic genes or viruses. In most cases, intravascular injection is the best delivery method to achieve the systemic distribution of viruses and to enable these agents to reach distant therapeutic sites. However, viruses administered by intravascular injection encounter overlapping barriers that impede their ability to reach their targets, including interactions with blood cells, blood factors and endothelial cells, loss to hepatocytes and macrophages, and destruction by innate and adaptive immune responses.

Comparison of replication-competent, first generation, and helper-dependent adenoviral vaccines.

All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice.

Short-term rescue of neonatal lethality in a mouse model of propionic acidemia by gene therapy.

Propionic acidemia (PA) is a metabolic disorder that causes mental retardation and that can be fatal if untreated. PA is inherited in an autosomal recessive fashion involving mutations in PCCA or PCCB encoding the alpha and beta subunits of propionyl-CoA carboxylase (PCC). Current treatment is based on dietary restriction of substrate amino acids, which attenuates symptoms.

Macrophage depletion combined with anticoagulant therapy increases therapeutic window of systemic treatment with oncolytic adenovirus.

Liver tropism of systemically delivered adenoviruses (Ad) represents a considerable challenge for their use as anticancer therapeutics. More than 90% of i.v.

Early postoperative assessment of coronary artery bypass graft patency and anatomy: value of contrast-enhanced 16-MDCT with retrospectively ECG-gated reconstructions.

Objective: The objective of our study was to assess early postoperative patency and anatomy of off-pump coronary artery bypass grafts (CABGs) using retrospectively ECG-gated MDCT.

Conclusion: Retrospectively ECG-gated MDCT is a promising noninvasive technique with which to assess early postoperative patency and anatomy of CABGs.

[Imaging of the pulmonary arteries: when, how and when?].

For several years, catheter angiography was the standard imaging technique used for evaluating the pulmonary arteries. Technical advances with computed tomography have had a significant impact on chest imaging, especially the increasing availability of multidetector row CT units. CT pulmonary angiography (CTPA) is now the first line imaging technique to evaluate pulmonary arterial diseases, including pulmonary embolus.

Sinus CT scans and mediator release in nasal secretions after nasal challenge with cypress pollens.

Background: Involvement of paranasal sinuses has been suggested in allergic rhinitis but not clearly demonstrated.

Aims: To investigate the relationship between intermittent allergic rhinitis and computerized tomography (CT).

Methods: Twenty patients with intermittent rhinitis and sensitized to cypress pollens underwent unilateral nasal provocation tests (NPTs) using increasing concentrations of cypress pollens out of the pollen season.

Wall mechanics of the stented extracranial carotid artery.

Background And Purpose: Abrupt compliance changes and concomitant nonlaminar flow patterns may contribute to endothelial dysfunction and subsequent neointimal thickening. The aim of this study was to test the feasibility of wall mechanics measurement using B-mode ultrasound image analysis by dedicated software in the stented human carotid artery.

Methods: Carotid Wallstents (Schneider) were placed in the extracranial carotid arteries of 15 patients.

Wall mechanics of the stented rabbit aorta: long-term study and correlation with histological findings.

Purpose: To evaluate long-term changes in arterial wall mechanics induced by stenting of the rabbit aorta.

Methods: Eighteen New Zealand white rabbits had initial stent deployment (3x8 mm Multilink) at 110% of the pre-stenting abdominal aortic diameter. Group A (n=10) had no postdeployment stent expansion and group B (n=8) had 30% overdilation of the stent.

[Value of thoracic CT in the management of severe hemoptysis].

Purpose: To assess the value of thoracic CT in the management of patients with severe hemoptysis.

Patients And Methods: Between January 1997 and January 2001, 62 patients were investigated for severe hemoptysis (>300 ml/24H). The protocol, performed before angiography and embolization, included bronchial fiberoptic examination (BFE) followed by thoracic spiral CT-angiography.

Arterial stenting and overdilation: does it change wall mechanics in small-caliber arteries?

Purpose: To evaluate changes in arterial wall mechanics induced by stent overdilation in the rabbit aorta.

Methods: Twenty New Zealand white rabbits had initial stent deployment (3-mm x 8-mm Multilink) at 10% overdilation. Group A (n=11) had no subsequent balloon expansion of the stent and Group B (n=9) had 30% overdilation of the stent.

Validation of a newly developed B-mode image-processing technique versus wall-tracking ultrasound for the study of wall mechanics in small-calibre arteries.

Purpose: To validate a newly developed image-processing technique for the assessment of arterial wall compliance and distensibility from non-invasive B-mode ultrasound compared with the invasive wall-tracking technique.

Materials And Methods: Arterial wall compliance and distensibility coefficient were measured invasively by wall-tracking with an ultrasonic transducer implanted on the vessel wall, and non-invasively by automatic processing of B-mode ultrasound images, with a dedicated workstation and software (IO 3.1, IODP, Paris).

[Dysfunctioning of central venous catheters: role of the radiologist].

Malfunctioning long-term central vein catheters are related to malposition, obstruction, mechanical problems and occlusion of the catheters. The diagnosis and the management of these disorders are based upon chest film examination, catheter or venous enhancement with contrast media. Vascular interventional radiology plays a major role in low invasive management of malfunctioning central vein catheters in hemodialysed patients: transfemoral malpositioned catheter manipulations, fibrin sleeve stripping, infusion of urokinase.

Reversible amiodarone-induced lung disease: HRCT findings.

The aim of this study was to describe thoracic high-resolution computed tomography (HRCT) findings of reversible amiodarone-induced lung disease (AILD). The thoracic HRCT of 20 symptomatic patients who were considered as having reversible AILD by the medical staff of our institution were retrospectively reviewed. The patient-selection criteria used were the development of new respiratory symptoms while receiving amiodarone, the exclusion of other respiratory and cardiac diseases, and the decrease of both respiratory symptoms and radiological abnormalities after cessation of amiodarone and corticotherapy.