Cationic phosphonolipids as nonviral gene transfer agents in the lungs of mice

With the aim of developing new gene transfer tools for treating CF with gene therapy, we have synthesized a novel family of molecules named cationic phosphonolipids. The most efficient among them were selected by in vitro screening to compare their activities in vivo in mouse lungs. We used a reporter gene whose activity was measured cytofluorimetrically (FACS-Gal assay) and by means of a chemiluminescence technique. These tests allowed us to identify the percentage of transfected cells and to quantify total beta-galactosidase in the lungs. This enabled us to identify two molecules, significantly efficient in comparison with DNA alone: GLB73 (p = 0.0015) and GLB253 (p = 0.007). Their use resulted in a time lag between transfection and maximum efficiency: maximum efficiency was observed 4 days after transfection with GLB73, whereas it was noticeable only on day 7 with GLB253. Moreover, from toxicity studies carried out in vivo, GLB73 seems to be nontoxic. In vivo results were correlated with in vitro results obtained with CF epithelial cell lines. Consequently, GLB73 is a potential candidate for phase I clinical trials in humans.     

Injuries of the distal finger

The distal finger is the most commonly injured part of the hand. Adequate initial care should lead to speedy recovery and minimal residual disability. Inadequate initial care or neglect upon the part of the patient can result in a painful and prolonged period of disability. The primary care physician sees and treats the vast majority of these injuries.     

Early development of spiny neurons in fish and mouse: morphometric measures of dendritic spine formation pattern

Positions of spines on apical dendrites were evaluated using 4 pattern analysis techniques: spine counts, variance/mean ratio, Lloyd's patchiness index, and nearest neighbor distance matrix. Spiny tectal interneurons from jewel fish (100, 130, 160 and 1550 days old), and layer V pyramidal cells in layer IV auditory cortex of CBA/J mice (100 and 450 days old) were studied. Fish's spines became more numerous and more clumped on distal dendritic strata during development, while mice lost dendritic spines with age. Both species developed a significantly regular spacing pattern between neighboring spines during development. These changes are explained in the context of spine function and a biophysical model of dendritic spine patterns.     

Effect of cholera toxin on intramembranous particles of a murine lymphoid cell line

A girl with non-contributory family history, at the age of 7 years developed a recurrent ataxic-spastic syndrome followed by disorders of consciousness and seizures. She died in a decerebrate state at the age of 10 9/12 years. Diffuse EEG abnormalities changed in accordance with the clinical course. CSF findings were always negative. Brain biopsy performed at the age of 9 5/12 years was non-diagnostic. No clinical signs of adrenal insufficiency were present. Neuropathological examination disclosed severe demyelination of the cerebral white matter with formation of large periventricular cavities, relative sparing of the subcortical arcuate fibers, and peripheral myelin breakdown of the orthochromatic (neutral fat) type. There was complete absence of inflammatory lesions, comparative preservation of axons and oligodendroglia with moderate astroglial reaction. The optic system and cerebellum were not involved. Additional postanoxic changes were seen in the thalamus and hippocampus. The sporadic case is suggested to represent a cavitating form of neutral fat (simple orthochromatic) leukodystrophy which is to be separated from Schilder's diffuse sclerosis and adrenoleukodystrophy. The etiology of the disorder is unknown.