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Biomedical subjects

Simon A Lewis

Publications and source records attributed to Simon A Lewis.

6 recordsLinked to original sources

Teaching medical students dermatology research skills: six years of experience with the University of Texas Medical Branch dermatology non-degree research honors program, 2001-2006.

Since 2001, the Department of Dermatology at The University of Texas Medical Branch in Galveston has participated in a campus wide non-degree honors research program developed to enhance the research skills of non-dual degree (MD/PhD) medical students. From 2001 through 2006, thirteen students completed the dermatology research program, and earned research honors at graduation. Seven student manuscripts have been published or are in press at peer-review journals and ten of twelve program participants who have applied for dermatology residency positions have been successful at the time of writing.

Animal Experimentation↗

Kinetics of urothelial ATP release.

Recent reports have proposed that the urothelium can sense mechanical stretch and communicate this information to sensory afferent neurons by the release of ATP into the vicinity of P2X-containing neurons. This report investigates the bidirectional release of ATP by in vitro rabbit urothelium. ATP was measured using the luciferin-luciferase assay. Immediately after washing of both sides of the epithelium, there was a linear increase in ATP content in the mucosal compartment with a rate of 23 +/- 6.5 fmol x min(-1) x cm(-2) (n = 18). Serosal ATP content increased as a saturating exponential function, suggesting a constant rate of release and degradation of ATP by ectonucleotidases/exonucleotidases. The presence of a serosal ectonucleotidase/exonucleotidases was demonstrated by the time-dependent decrease in exogenously added ATP. The maximum rate of hydrolysis was 11 pmol x min(-1) x cm(-2) with a K(m) of 0.49 microM. The time course of serosal ATP release was modeled as a constant rate of release (d: mol x min(-1) x cm(-2)) and rate constant of hydrolysis (k(h): min(-)). In control conditions d was 18 fmol x min(-1) x cm(-2) and k(h) of 0.056 +/- 0.01 min(-) (n = 18). Steady-state serosal chamber content is 370 +/- 90 fmol/cm(2), and concentration is 50 +/- 1.2 x 10(-12) M. Stretching the tissue resulted in a transient fivefold increase in the rate of mucosal ATP release and a transient sixfold increase in serosal ATP release. Half-osmotic strength solutions increased mucosal release by 10-fold and serosal release by 5-fold. Tissue damage resulted in a step-increase in mucosal chamber ATP content by 6.6 +/- 1 pmol/cm(2) and serosal chamber ATP by 0.1 +/- 0.06 pmol/cm(2) (n = 5).

Adenosine Triphosphate↗

Indocyanine green alters transepithelial electrical parameters of the distal colon.

Indocyanine green (ICG) is used as a dye marker of the vascular space in gastroenterology, ophthalmology, neurology, and critical care medicine. It is widely regarded to be inert. We report, however, that ICG demonstrates effects on colonic transepithelial electrical parameters which could form a basis for a growing number of deleterious gastrointestinal and other clinical effects. Short-circuit current (Iscc), transepithelial conductance (gt), and transepithelial paracellular flux of 14C-D-mannitol were monitored across sheets of rat distal colon. Dye was introduced to mucosal or serosal tissue surfaces at a concentration similar to that used in vivo (10 microg/ml). ICG decreased Iscc by over 50% and gt by over 10%. Transepithelial mannitol flux was not altered. Dye was effective only from the serosal surface. Cyclic AMP-induced spiking of Iscc was not affected by ICG. Preincubation with amiloride or furosemide did not affect the action of the dye on gt or Iscc. ICG at in vivo dosages is clearly capable of inhibiting ion transport across colon epithelial tissue. The serosal site of action indicates activity on a basal-lateral transport system or diffusion into the cell only across the basal-lateral membrane followed by inhibition of a transporter from the intracellular side. ICG should not be considered inert in vivo. Leakage of ICG from the vascular space into the interstitial fluid space will likely result in tissue morbidity.

Animals↗

Colistin interactions with the mammalian urothelium.

Here we describe the effect of colistin on the barrier function of the mammalian urinary bladder epithelium. Addition of colistin to the mucosal solution of the rabbit urinary bladder epithelium (urothelium) resulted in an increase in the transepithelial conductance. The magnitude of the increase in transepithelial conductance was dependent on the membrane voltage, concentration of colistin, and presence of divalent cations in the bath solution. The initial site of action of colistin was at the apical membrane. Colistin increased the membrane conductance only when the apical membrane potential was cell interior negative. The more negative the membrane potential, the larger the conductance increase. The concentration dependence of the conductance increase saturated, suggesting a membrane binding site. Divalent cations decreased the magnitude of the conductance increase. This divalent cation action occurred at two sites: one in competition with colistin for a membrane binding site, and the other by rapidly blocking the induced conductance. At short exposure times, the increase in conductance was reversed by either removing colistin from the bath or changing the voltage so that the apical membrane was cell interior positive. At long exposure times, the increase was only partially reversible by voltage or removal from the bath. This finding suggests that at long exposure times, there is a toxic effect of colistin on the urothelium.

Animals↗

The N-terminal domain of vimentin alters bladder permeability.

PURPOSE: We assessed the effect of the vimentin amino terminal polypeptide (NT1) on barrier function of rabbit bladder epithelium. MATERIALS AND METHODS: The effect of NT1 on the properties of rabbit bladder epithelium were studied using Ussing chambers and electrophysiological methods. RESULTS: NT1 increased transepithelial conductance (Gt) in a voltage dependent manner. At a transepithelial voltage (Vt) of -70 mV (serosal solution ground) the addition of NT1 to mucosal solution did not result in a change in Gt. When Vt was clamped to 0 mV, there was a time dependent increase in Gt. The increase in Gt was reversed by clamping Vt back to -70 mV or by removing NT1 from the mucosal bath at 0 mV. The polypeptide acts primarily at the apical membrane with a conductance increase that is concentration dependent. Induced conductance is nonselective for small monovalent cations and anions. The ability of NT1 to increase membrane conductance was decreased in the presence of bath calcium. CONCLUSIONS: The data suggest that the amino terminus of vimentin can interact with the plasma membrane of bladder epithelium and increase ion permeability in a voltage dependent manner.

Animals↗