124 research outputs found
The morphology of human rod ERGs obtained by silent substitution stimulation
YesPurpose To record transient ERGs from the lightadapted
human retina using silent substitution stimuli
which selectively reflect the activity of rod photoreceptors.
We aim to describe the morphology of these
waveforms and examine how they are affected by the
use of less selective stimuli and by retinal pathology.
Methods Rod-isolating stimuli with square-wave
temporal profiles (250/250 ms onset/offset) were
presented using a 4 primary LED ganzfeld stimulator.
Experiment 1: ERGs were recorded using a rodisolating
stimulus (63 ph Td, rod contrast,
Crod = 0.25) from a group (n = 20) of normal
trichromatic observers. Experiment 2: Rod ERGs
were recorded from a group (n = 5) using a rodisolating
stimulus (Crod = 0.25) which varied in
retinal illuminance from 40 to 10,000 ph Td. Experiment
3: ERGs were elicited using 2 kinds of nonisolating
stimuli; (1) broadband and (2) rod-isolating
stimuli which contained varying degrees of L- and
M-cone excitation. Experiment 4: Rod ERGs were
recorded from two patient groups with rod monochromacy
(n = 3) and CSNB (type 1; n = 2).
Results The rod-isolated ERGs elicited from normal
subjects had a waveform with a positive onset
component followed by a negative offset. Response
amplitude was maximal at retinal illuminances\100
ph Td and was virtually abolished at 400 ph Td. The
use of non-selective stimuli altered the ERG waveform
eliciting more photopic-like ERG responses. Rod
ERGs recorded from rod monochromats had similar
features to those recorded from normal trichromats, in
contrast to those recorded from participants with
CSNB which had an electronegative appearance.
Conclusions Our results demonstrate that ERGs
elicited by silent substitution stimuli can selectively
reflect the operation of rod photoreceptors in the
normal, light-adapted human retina.Deutsche Forschungsgemeinschaft (DFG) (KR1317/13-1) and Bundesministerium für Bildung und Forschung (BMBF) (01DN14009) provided financial support for JK
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Structure and Inhibition of the SARS Coronavirus Envelope Protein Ion Channel
The envelope (E) protein from coronaviruses is a small polypeptide that contains at least one α-helical transmembrane domain. Absence, or inactivation, of E protein results in attenuated viruses, due to alterations in either virion morphology or tropism. Apart from its morphogenetic properties, protein E has been reported to have membrane permeabilizing activity. Further, the drug hexamethylene amiloride (HMA), but not amiloride, inhibited in vitro ion channel activity of some synthetic coronavirus E proteins, and also viral replication. We have previously shown for the coronavirus species responsible for severe acute respiratory syndrome (SARS-CoV) that the transmembrane domain of E protein (ETM) forms pentameric α-helical bundles that are likely responsible for the observed channel activity. Herein, using solution NMR in dodecylphosphatidylcholine micelles and energy minimization, we have obtained a model of this channel which features regular α-helices that form a pentameric left-handed parallel bundle. The drug HMA was found to bind inside the lumen of the channel, at both the C-terminal and the N-terminal openings, and, in contrast to amiloride, induced additional chemical shifts in ETM. Full length SARS-CoV E displayed channel activity when transiently expressed in human embryonic kidney 293 (HEK-293) cells in a whole-cell patch clamp set-up. This activity was significantly reduced by hexamethylene amiloride (HMA), but not by amiloride. The channel structure presented herein provides a possible rationale for inhibition, and a platform for future structure-based drug design of this potential pharmacological target
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