Biomedical subjects

B D Wolf

Publications and source records attributed to B D Wolf.

4 recordsLinked to original sources

PubMed2000

Axon pathfinding proceeds normally despite disrupted growth cone decisions at CNS midline.

Axons in the bilateral brain of Drosophila decide whether or not to cross the midline before following their specific subsequent pathways. In commissureless mutants, the RP3 and V motoneuron axons often fail to cross the midline but subsequently follow the mirror-image pathways and innervate corresponding muscle targets on the ipsilateral side. Conversely, in roundabout mutants, the RP2 and aCC motoneuron axons sometimes cross the midline abnormally but their subsequent pathways and synaptic targeting are the perfect mirror images of those seen in wild type. Furthermore, within a single segment of these mutants, bilateral pairs of motoneuron axons can make their midline decisions independently of each other. Thus, neither the growth cones' particular molecular experience nor the decision at the midline caused by these mutations affects their ability to respond normally to subsequently presented cues.

Animals↗

PubMed1995

Osmotic stress sensitizes sterol-free phospholipid bilayers to the action of Amphotericin B.

We have tested the ability of Amphotericin B to form ion channels/defects in osmotically stressed large unilamellar vesicles (LUV) using pyranine fluorescence detected ion/H+ exchange. We found that sterol-free LUV exhibit greatly increased sensitivity to AmB channel formation in the soluble oligomer state (> 0.5 microM) under modestly hypoosmotic conditions (< 100 delta mosM). These vesicles are completely insensitive under isoosmotic conditions. The related antibiotics, Amphotericin B methyl ester and Nystatin showed almost no activity under hypoosmotic conditions in the absence of sterol. This difference may be attributable to differences in solution oligomeric states. Experiments with KCl and CaCl2 internal buffers demonstrate that these sterol-free AmB membrane disruptions are highly selective for monovalent cations (K+) over anions (Cl-), ruling out massive lysis or unselective membrane defects caused by osmotic pressure. Thus, AmB seems to be acting as a 'molecular harpoon', an expression coined to describe substances which can selectively target osmotically stressed, strained or highly curved membranes. These results may provide a rationale for AmB's reported anti-HIV activity and reported activity against sterol-free small unilamellar vesicles (highly curved membranes) as well as the reduced activity of liposomal drug delivery systems toward cholesterol-containing and sterol-free membranes (fewer soluble oligomers).

Amphotericin B↗

PubMed1993

Temperature effects on the aggregation state and activity of amphotericin B.

Amphotericin B (AmB) in aqueous solution becomes less aggregated as temperature is increased as measured by CD spectroscopy. Concomitantly, AmB's ability to induce K+ leakage from cholesterol-containing large unilamellar vesicles (LUV) decreases 4-fold per 10 degrees C increase. In contrast, ergosterol-containing vesicles show no clear trend in their temperature sensitivity to AmB action. These data strongly support a model of AmB action where drug aggregates and not monomers are the major channel-inducing species against cholesterol- but not ergosterol-containing membranes.

Amphotericin B↗

PubMed1985

Software for electrophysiological experiments with a personal computer.

These programs were written for the IBM personal computer equipped with a Tecmar Labmaster analog interface board. The software operates under the MS-DOS operating system; it is written in compiled BASIC and employs short machine-language subroutines for crucial functions. Details are presented on the analog interface routines which make special use of the 9513 counter/timer chip on the Labmaster. Time resolution is about 32 microseconds per sample on the PC and 15 microseconds on the PC/AT. One series of programs performs traditional voltage- and current-clamp experiments on macroscopic currents in whole cells. A second series interfaces with a hardware window discriminator to capture single-channel events in a recirculating buffer; a stimulus can be triggered to fire during an open channel. Off-line programs perform standard analyses, and further processing can be performed with standard spreadsheet programs.

Animals↗