Biomedical subjects
Publications and source records attributed to J Ong.
The authors report a rare case of an ovarian tumor metastasizing to the dura at L2-L3. It was seen at myelography to be intradural and by CT to be within the spinal canal. The latter exam eliminated a lipoma or a dermoid (both possible intradural or extramedullary-intradural tumor) from consideration.
(R,S)-4-Amino-3-(7-methylbenzo[b]furan-2-yl)-butanoic acid (7-MBFG), a new benzofuran analogue of the GABA(B) receptor agonist baclofen, has been evaluated for pharmacological activity on GABA(B) receptors in the guinea-pig isolated ileum and rat neocortical slices. 7-MBFG (300 and 500 microM) reversibly antagonized the (R,S)-baclofen induced depression of cholinergic twitch contractions in the guinea-pig ileum and shifted the concentration-response curve for baclofen to the right, in a parallel manner, giving an apparent pA2 value of 3.7+/-0.3. Likewise, 7-MBFG (300 and 500 microM) reversibly blocked the baclofen-induced suppression of spontaneous discharges, in rat neocortical slices maintained in Mg2+ -free Krebs medium, and caused a rightward, parallel shift of the baclofen concentration-response curve, giving an apparent pA2 value of 4.1+/-0.1. The compound 7-MBFG belongs to a novel, new class of antagonist at central and peripheral GABA(B) receptors, in which the antagonist properties reside in the pseudo-aromatic character of their 3-benzo[b]furan-2-yl substituents, and might provide useful leads for further development of GABA(B) receptor ligands.
The mammalian forebrain subventricular zone (SVZ) contains stem cells capable of generating new neurons and glia. Recent studies indicate that acute brain injury is a potent stimulus for SVZ stem cell proliferation. To better understand mechanisms of the SVZ response to neonatal brain injury, we used a model that focuses on a unique mechanism of vulnerability of the immature CNS, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excitotoxicity. We previously demonstrated that intracerebroventricular injection of the glutamate analog AMPA in rats at postnatal day 7 (P7) caused bilateral periventricular gray and white matter injury. We hypothesized that excitotoxic injury would stimulate cellular proliferation in the SVZ; we used the AMPA intracerebroventricular injection model to test this hypothesis. P7 rat pups received either left or right intracerebroventricular injections of S-AMPA (2.5 nmol). Normal and PBS-injected littermates were included as controls. On P8 or P14, serial coronal sections through the SVZ were collected; an immunohistochemical assay was performed with an antibody to the cell proliferation marker Ki-67. Bilateral Ki-67+ cells/SVZ were quantitated stereologically using the optical disector method. The median number of Ki-67+ cells/SVZ was increased in the SVZ of AMPA-injected rats relative to normal controls on both P8 and P14. To evaluate neurogenesis, we assayed the expression of doublecortin, a microtubular protein expressed only by immature neurons. From P8 to P14, there was a marked increase in doublecortin immunoreactive cells in the AMPA-injected SVZ. Many Ki-67+ nuclei were immediately surrounded by doublecortin staining. This study indicates that there is a proliferative response in the immature SVZ after an excitotoxic stimulus. Our findings suggest that some of these newly generated cells differentiate as immature neurons. This model may provide information about the mechanisms that regulate SVZ responses to neonatal brain injury.