Biomedical subjects

Jennifer A Kim

Publications and source records attributed to Jennifer A Kim.

3 recordsLinked to original sources

PubMed2006

Retinoids restore normal cyclic nucleotide sensitivity of mutant ion channels associated with cone dystrophy.

PURPOSE: To determine whether inhibition of cyclic nucleotide-gated (CNG) ion channels by retinoids might be useful in treating degenerative retinal diseases in which either the CNG channels are hypersensitive to 3',5'-cyclic guanosine monophosphate (cGMP) or the photoreceptor cGMP concentration is elevated. METHODS: Patch clamp (electrophysiological) methods were used to measure activation by cGMP of wild-type human cone (hCNGA3), mutant cone (hCNGA3-N471S), and wild-type bovine rod (bCNGA1) CNG channels heterologously expressed in Xenopus oocytes. Cyclic GMP-activated currents were measured in excised, inside-out membrane patches before and after treatment with either all-trans retinal (ATR) or all-trans C22 aldehyde, which is too long to fit into the chromophore binding pocket of opsin and therefore cannot activate the visual transduction cascade. RESULTS: At physiological cGMP concentrations, 150 nM ATR reduced the open probability of the mutant cone CNG channel by reducing its apparent cGMP affinity to that of the normal cone channel. Furthermore, all-trans C22 aldehyde similarly inhibited the mutant cone channel as well as normal rod and cone CNG channels. CONCLUSIONS: Our results raise the possibility that retinoids, such as all-trans C22 aldehyde, that inhibit CNG channels without affecting the transduction cascade, may be useful in treating degenerative retinal diseases in which either the cGMP concentration is elevated or the CNG channels are hypersensitive to cGMP.

Animals↗

PubMed2005

Movement quantity and frequency coding in human motor areas.

Studies of movement coding have indicated a relationship between functional MRI signals and increasing frequency of movement in primary motor cortex and other motor-related structures. However, prior work has typically used block-designs and fixed-time intervals across the varying movements frequencies that may prevent ready distinction of brain mechanisms related to movement quantity and, especially, movement frequency. Here, we obtained functional MRI signals from humans working in an event-related design to extract independent activation related to movement quantity or movement frequency. Participants tapped once, twice, or thrice at 1, 2, or 3 Hz, and the tapping evoked activation related to movement quantity in the precentral and postcentral gyri, supplementary motor area, cerebellum, putamen, and thalamus. Increasing movement frequency failed to yield activation in these motor-related areas, although linear movement frequency affects occurred in nonmotor regions of cortex and subcortex. Our results do not replicate prior data suggesting movement frequency encoding in motor-related areas; instead we observed movement quantity coding in motor-related brain areas. The discrepancy between prior studies and this study likely relates to methodology concerns. We suggest that the movement quantity relationships in human motor areas and encoding of movement frequency in nonmotor areas may reflect a functional anatomical substrate for mediating distinct movement parameters.

Adult↗

PubMed2004

Nodulisporic acids D-F: structure, biological activities, and biogenetic relationships.

Nodulisporic acids D, E, and F are the newest members of a family of nontremorogenic indole-diterpenoids that are potent, orally bioavailable, antiflea agents derived from a fungus belonging to the genus Nodulisporium. The four members of the D series are each devoid of an isoprene residue that is present at C-26 in the three nodulisporic acids described originally (the A series). Nodulisporic acid E (11a) has a simpler structure, which lacks not only the isoprene residue at C-26 but also two that form the A/B rings. Nodulisporic acid F is the simplest of all nodulisporic acids and is devoid of all three isoprene residues of the indole unit; as such, it represents the earliest biosynthetic intermediate in this series. A biogenetic grid based on mutation studies is proposed that encompasses all the known nodulisporic acids. Structure-activity relationships of the known natural nodulisporic acids have been elucidated. Within a series the most active compound possesses a dienoic acid chain, and overall, the end product of the biogenetic grid, i.e., nodulisporic acid A, exhibits the most potent antiflea activity. Additionally, the stereochemistries of C-3' ' and C-4' ' of nodulisporic acid D(2) and therefore of nodulisporic acids A(2), B(2), and C(2) have been assigned.

Animals↗