Increased expression of NGFI-A mRNA in the rat striatum following burst stimulation of the medial forebrain bundle

Using in situ hybridization, we examined the mRNA expression for several immediate early genes in dopamine-innervated brain areas following electrical burst vs. regular stimulation of the medial forebrain bundle in anaesthetized rats. Two hours after 5 Hz burst stimulation, the expression of the nerve growth factor-inducible clone A (NGFI-A) mRNA was increased in the medial part of the striatum. This increase was prevented by pretreatment with the dopamine-D1 receptor antagonist, SCH23390 (0.1 mg/kg i.p.). After 8 Hz burst stimulation, NGFI-A mRNA expression was increased in the medial, central and lateral parts of the striatum. Induction occurred predominantly in cells expressing mRNAs for the dopamine-D1 receptor, substance P and dopamine and cAMP-regulated phosphoprotein (DARP-32). Regular stimulation had no effect on NGFI-A mRNA expression. The induction of NGFI-A was related to the levels of dopamine released by burst or regular stimulation as demonstrated with in vivo amperometry. Two hours after stimulation, the expression of none of the other genes studied was altered. One hour after 8 Hz burst stimulation, the expression of NGFI-A, NGFI-B and jun-B mRNAs was increased in the striatum and that of NGFI-A, NGFI-B, c-fos, fos-B and jun-B mRNAs was variably increased in the nucleus accumbens and lateral septum. These results provide additional support for the physiological importance of burst firing activity in midbrain dopamine neurons for the activation of their target cells. They demonstrate a spatial and temporal specificity as regards the brain region, the gene activated, the receptor involved and the phenotype of the cells affected.     

Estimation of the benefit of bone-anchored hearing aids

Implantable bone conduction hearing aids are a valuable alternative to conventional aids for those who cannot use a conventional air conduction aid or find it difficult to use because of an aural discharge, most commonly due to chronic otitis media. Previously reported series of the use of a bone-anchored hearing aid (BAHA) come from the originators of this device, and an independent report of their benefit and use, especially in previous air conduction aid users, would be of value. Twenty-three patients were evaluated at least 6 months after implantation of a BAHA. All 7 previous bone conduction aid users were delighted with their BAHA, reporting increased comfort and hearing benefit that was backed by audiometric evidence. Of the 16 individuals who previously used an air conduction aid, 11 (69%) were delighted users of their BAHA. Unfortunately, the other 5 (31%) reverted to solely using their air conduction aid. There was no obvious predictor as to how these individuals might have been identified prior to implantation. In particular, their pure tone thresholds, especially the bone conduction thresholds, were no different from those of the 11 BAHA users. However, in free field audiometry, the users gained superior benefit from their BAHA compared to their air conduction aid, whereas the nonusers did not. In conclusion, in all series to date, previous users of a conventional bone conduction aid have been delighted users of a BAHA and have gained superior audiometric benefit. This is not necessarily the case with previous air conduction aid users.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms of spectral tuning in blue cone visual pigments. Visible and raman spectroscopy of blue-shifted rhodopsin mutants

Spectral tuning by visual pigments involves the modulation of the physical properties of the chromophore (11-cis-retinal) by amino acid side chains that compose the chromophore-binding pocket. We identified 12 amino acid residues in the human blue cone pigment that might induce the required green-to-blue opsin shift. The simultaneous substitution of nine of these sites in rhodopsin (M86L, G90S, A117G, E122L, A124T, W265Y, A292S, A295S, and A299C) shifted the absorption maximum from 500 to 438 nm, accounting for 2,830 cm-1, or 80%, of the opsin shift between rhodopsin and the blue cone pigment. Raman spectroscopy of mutant pigments shows that the dielectric character and architecture of the chromophore-binding pocket are specifically altered. An increase in the number of dipolar side chains near the protonated Schiff base of retinal increases the ground-excited state energy gap via long range dipole-dipole Coulomb interaction. In addition, the W265Y substitution causes a decrease in solvent polarizability near the chromophore ring structure. Finally, two substitutions on transmembrane helix 3 (A117G and E122L) act in combination with the other substitutions to alter the binding-pocket structure, resulting in stronger interaction of the protonated Schiff base group with the surrounding dipolar groups and the counterion. Taken together, these results identify the amino acid side chains and the underlying physical mechanisms responsible for a majority of the opsin shift in blue visual pigments.     

Toxic properties of Beauveria pigments on erythrocyte membranes

The Beauveria pigments, tenellin, bassianin and oosporein, all inhibited total erythrocyte membrane ATPase activity in a dose-dependent manner by as much as 50% at 200 micrograms/ml. These pigments inhibited Ca(2+)-ATPases to a greater extent than Na+/K(+)-ATPase activity. The ATPase inhibitory activity for these pigments was not specific but was probably a consequence of membrane disruption, since pigments all caused alterations in erythrocyte morphology and promoted varying degrees of cell lysis.     

Effects of endothelin-1 on renal microvasculature measured using quantitative ultrasound

Renal vascular resistance is an important feature of kidney function and disease. To maintain adequate blood flow, renal vascular resistance varies in response to changes in systemic pressure. Vascular resistance is largely determined by arteriolar diameter, which is regulated by local and systemic factors. We used quantitative ultrasound techniques to follow renal vascular changes in anesthetized dogs during local intraarterial infusion of a potent vasoconstrictor, endothelin-1 (ET-1). Average arteriolar diameters were estimated by analyzing echo-signal spectra (5-15 MHz) obtained from renal cortex in vivo before, during, and after ET-1 infusion. At calculated arterial concentrations of 0.01 nM, 0.1 nM, and 1.0 nM, ET-1 reduced the average arteriolar diameter of 38 +/- 2 microns by 2%, 63%, and 91%, respectively, without producing a significant change in systemic blood pressure. Changes in scatterer size were consistent with the observed changes in renal hemodynamics detected using Doppler techniques. In addition, acoustic attenuation was found to increase with ET-1 concentration. These data suggest that quantitative ultrasound methods are sensitive to changes in renal arteriolar diameter, and may be a new noninvasive method for continuously monitoring changes in vascular resistance.