ABSTRACT
With the goal of optimizing adenovirus-mediated suicide gene therapy for prostate cancer, we have developed a method based on the human sodium iodide symporter (hNIS) that allows for noninvasive monitoring of adenoviral vectors and quantification of gene expression magnitude and volume within the prostate. A replication-competent adenovirus (Ad5-yCD/mutTK(SR39)rep-hNIS) coexpressing a therapeutic yeast cytosine deaminase (yCD)/mutant herpes simplex virus thymidine kinase (mutTK(SR39)) fusion gene and the hNIS gene was developed. Ad5-yCD/mutTK(SR39)rep-hNIS and a replication-defective hNIS adenovirus (rAd-CMV-FLhNIS) were injected into contralateral lobes of the dog prostate and hNIS activity was monitored in live animals following administration of Na(99m)TcO(4) using gamma camera scintigraphy. Despite the close proximity of the urinary bladder, (99m)TcO(4)(-) uptake was readily detected in the prostate using viral dose levels (10(10) to 10(12) viral particles) that have been safely administered to humans. Due to its rapid clearance and short physical half-life (6 h), it was possible to obtain daily measurements of (99m)TcO(4)(-) uptake in vivo, allowing for dynamic monitoring of reporter gene expression within the prostate as well as biodistribution throughout the body. High-resolution autoradiography of prostate sections coupled with 3D reconstruction of gene expression demonstrated that the magnitude and volume of gene expression could be quantified with submillimeter resolution. Implementation of the GENIS (gene expression of Na/I symporter) technology in the clinic will facilitate optimization of future human gene therapy trials.
Subject(s)
Diagnostic Imaging , Genetic Therapy , Genetic Vectors , Symporters/genetics , Adenoviridae , Animals , Dogs , Humans , Liver/pathology , Male , Mice , Prostate/pathology , Symporters/metabolism , Technetium Compounds/metabolismABSTRACT
Congenital lobar emphysema has the clinical features of an air block' syndrome with- out the evidence of pulmonary infection or intrabronchial foreign body. The hyperinflated lung causes a compression of uninvolved lobes creating respiratory distress, cyanosis within the first weeks of life. We experienced a case of congenital lobar emphysema diagnosed incidentally by chest reontgenogram in an infant with frequent upper respiratory infection within a few weeks of life. Chest X-ray revealed extensive emphysematous changes in the left upper lobe, shifting of heart and medistinum to the right and compression of the right lung. Respiratory distress, cyanosis and chest wall retraction ensued and left upper lobe Lobectomy was performed successfully.
Subject(s)
Humans , Infant , Cyanosis , Emphysema , Foreign Bodies , Heart , Lung , Thoracic Wall , ThoraxABSTRACT
Intravascular lymphomatosis(IVL) which was first described by pfleger and Tappeiner in 1959 is rare malignancy characterized by neoplastic proliferation of lymphoid cell lineage within the vascular lumen with little or no adjacent parenchymal involvement. Its usual sites of involvement are central nervous system and skin or infrequently heart, lungs, pancreas, liver, spleen, kidney, adrenal glands, genitourinary tract, and bone marrow. Pulmonary involvement of IVL is not common. Symptoms of pulmonary involvement include dyspnea, cough and fever. Radiologicially, the disease is manifested with diffuse interstitial infiltrates. We report a recently experienced case of pulmonary intravascular lymphomatosis which was manifested with fever and chest pain.
