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L Lenaerts

Publications and source records attributed to L Lenaerts.

11 recordsLinked to original sources
PubMed2006

Mouse adenovirus type 1 attachment is not mediated by the coxsackie-adenovirus receptor.

Common human adenovirus (Ad) vectors are derived from serotype 2 or 5, which use the coxsackie-adenovirus receptor (CAR) as their primary cell receptor. We investigated the receptor usage of mouse adenovirus type 1 (MAV-1), which in vivo is characterized by a pronounced endothelial cell tropism. Alignment of the fiber knob sequences of MAV-1 and those of CAR-using adenoviruses, revealed that amino acid residues, critical for interaction with CAR, are not conserved in the MAV-1 fiber knob. Attachment of MAV-1 to Chinese hamster ovary (CHO) cells was not increased by stable transfection with mouse CAR, whereas the binding efficiency of Ad2 was 20-fold higher in the mouse CAR-transfectant compared to the wild type cells. Also, purified fiber knob of Ad5, which is interchangeable with the Ad2 fiber knob, did not compete with MAV-1 for receptor binding, indicating that MAV-1 binds to a receptor different from CAR. These results support further exploration of an MAV-1-derived vector as a potential vehicle for gene delivery to cell types which are not efficiently transduced by human adenovirus vectors.

Adenoviridae↗
PubMed2006

Antiviral therapy for adenovirus infections.

The treatment of severe adenovirus keratoconjunctivitis and life-threatening adenovirus infections in immunocompromised patients is still unsatisfactory. We here review the mode of action and antiviral data for cidofovir and ribavirin, obtained in cell culture, animal models or patients. Several nucleoside or nucleotide analogues have been described that target the adenovirus polymerase, whereas other antiviral targets have been poorly investigated. Furthermore, optimal therapeutic response may be achieved by combining antiviral therapy with immunotherapeutic approaches, as currently being explored.

Adenovirus Infections, Human↗
PubMed2005

Mouse adenovirus type 1 infection in SCID mice: an experimental model for antiviral therapy of systemic adenovirus infections.

The importance of human adenovirus infections in immunocompromised patients urges for new and adequate antiadenovirus compounds. Since human adenoviruses are species specific, animal models for systemic adenovirus infections rely on a nonhuman adenovirus. We established mouse adenovirus type 1 (MAV-1) infection of BALB/c SCID mice as a model for the evaluation of antiadenovirus therapy. In vitro studies with mouse embryonic fibroblasts pointed to the acyclic nucleoside phosphonate cidofovir and the N-7-substituted acyclic derivative 2-amino-7-(1,3-dihydroxy-2-propoxymethyl)purine (S-2242) as markedly active compounds against MAV-1. SCID mice, infected intranasally with MAV-1, developed a fatal disseminated infection after approximately 19 days, characterized by hemorrhagic enteritis. Several techniques were optimized to monitor viral, immunological, and pathological aspects of MAV-1 infection. Real-time PCR quantification of viral DNA revealed that after replication in the lungs, virus disseminated to several organs, including the brain, liver, spleen, intestine, heart, and kidneys (resulting in viruria). Immunohistochemical staining showed that MAV-1 was localized in the endothelial cells of the affected organs. Using reverse transcription-PCR, tissue levels of proinflammatory cytokines (i.e., interleukin-1beta and tumor necrosis factor alpha) were found to be markedly increased. The MAV-1/SCID model appears to be an appropriate model for in vivo evaluation of antiadenovirus agents. Treatment with cidofovir or S-2242 at a dose of 100 mg per kg of body weight resulted in a significant delay in MAV-1-related death, although these antivirals were unable to completely suppress virus replication despite continued drug treatment. These findings suggest that complete virus clearance during antiviral therapy for disseminated adenovirus infection may require an efficient adaptive immune response from the host.

3T3 Cells↗
PubMed2005

Antiadenovirus activities of several classes of nucleoside and nucleotide analogues.

The absence of any formally licensed antiadenovirus drugs and the increasing incidence of life-threatening adenovirus infections in immunosuppressed patients warrant the development of effective antiadenovirus compounds. A detailed study was performed on the antiadenovirus activities of several classes of nucleoside and nucleotide analogues in human embryonic lung fibroblast cells. The antiadenovirus activities were evaluated by three methods, viz., evaluating the adenoviral cytopathic effect, monitoring cell viability by a colorimetric assay, and real-time PCR quantitation of viral DNA as a direct parameter for virus replication. The most active and selective compounds were the acyclic nucleoside phosphonate analogues cidofovir, its adenine analogue (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], and the new derivative (S)-2,4-diamino-6-[3-hydroxy-2-(phosphonomethoxy)propoxy]pyrimidine [(S)-HPMPO-DAPy]; the N7-substituted acyclic derivative 2-amino-7-(1,3-dihydroxy-2-propoxymethyl)purine (S-2242); and the 2',3'-dideoxynucleoside analogues zalcitabine and alovudine. No antiadenovirus activity was observed for the antiviral drugs ribavirin, foscarnet, acyclovir, penciclovir, and brivudin, while ganciclovir displayed modest activity. However, in human osteosarcoma cells transfected with herpes simplex virus thymidine kinase, ganciclovir demonstrated highly potent antiadenovirus activity, suggesting that the efficacy of ganciclovir against adenovirus is limited by inefficient phosphorylation in adenovirus-infected cells, rather than by insufficient inhibition at the viral DNA polymerase level. Collectively, our antiviral data show that the adenovirus DNA polymerase exhibits sensitivity to a relatively broad spectrum of inhibitors and should be studied further as an antiviral target in antiadenovirus drug development programs.

Adenoviridae↗
PubMed1998

Cerebral venous thrombosis and procoagulant factors--a case study.

Cerebral venous thrombosis is a polymorphic clinical entity for which diagnosis has become more frequent with the advent of neuroradiology. The superior sagittal and transverse sinuses are frequently involved, whereas cavernous sinus thrombosis is much less frequent. Inherited resistance to the anticoagulant action of activated protein C (APC resistance), antithrombin deficiency, protein C and S deficiencies, and hyperhomocysteinemia seem to represent major causes of thrombophilia when unusual thromboembolic events (ie, before the age of 45 years) are observed. The authors present the combined occurrence of protein C and protein S deficiencies in a 32-year-old woman, manifested by extensive cerebral venous thrombosis.

Adult↗
PubMed1992

Molecular basis for differences in susceptibility to coal workers' pneumoconiosis.

It is generally accepted that there are differences among workers in susceptibility towards the effects of mineral dusts such as silica, coal dust and asbestos. Basic research continues to find new factors involved in the process of pulmonary fibrosis caused by these minerals. In this paper, two hypotheses implicitly generated by recent findings were tested in two case-control studies among coal miners: generation of tumour necrosis factor (TNF) by blood monocytes of miners with coal workers' pneumoconiosis (CWP) and serum type III procollagen peptide (PIIIP) in CWP. Our data indicate that both parameters can be used as biological markers for early diagnosis of CWP. A follow-up study is described in which the predictive power of increased TNF release and serum PIIIP as risk factor to develop lung fibrosis will be assessed.

Adult↗
PubMed1992

Acutely symptomatic benign mediastinal cysts.

Usually, cystic mediastinal masses are considered as benign. However, the size of the cyst is of importance, chiefly in a closed space such as the superior mediastinum. Rarely a dramatic symptomatology may develop though this was the case in the two patients we describe, who were admitted in the department. In the first case (a parathyroid cyst), the symptoms were due to a thrombosis of the left innominate vein, and in the second case (a thyroid cyst), the severity was dominated by a dramatic compression of the trachea and the vessels. The contribution of computed tomography is nowadays undisputed. It enables the diagnosis of the cystic nature before surgery. The diagnosis can easily be confirmed by percutaneous drainage.

Acute Disease↗
PubMedDate not supplied

Airflow obstruction and monocyte TNF release in coal workers.

Respiratory health of 102 retired coal miners was assessed by chest radiographs, lung function measurements, and questionnaires, and related to tumor necrosis factor-alpha (TNF-alpha) production by blood monocytes upon priming with different stimuli. The objective was to assess a possible relationship between airflow obstruction and TNF-alpha production in retired coal workers. No significant differences in lung function were observed between cases of coal workers' pneumoconiosis (CWP) (n = 27; > %) and references (n = 75; = > %), nor was the effect of cumulative exposure on flow volume or impedance parameters significant. TNF-alpha release upon stimulation of blood monocytes with coal mine dust was significantly increased in cases with International Labour Organisation (ILO) score 0/1 (doubtful cases) compared to references and cases with a higher ILO score. Airflow limitation defined either as a FEV1 < 80% (N = 10; 5 cases of CWP) or as a resonance frequency > 15 Hz accompanied by a negative frequency dependence of resistance (N = 9; 4 cases of CWP) was significantly related to high levels of TNF-alpha release upon stimulation with endotoxin and silica, with silica showing the strongest relation. These data suggest that in this group airflow limitation is associated with an increased expression of inflammatory mediators indifferent of the presence of pneumoconiosis.

Airway Obstruction↗