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Biomedical subjects

G Matthews

Publications and source records attributed to G Matthews.

At least 109 records · Page 6Linked to original sources
PubMed1988

Activation of single ion channels from toad retinal rod inner segments by cyclic GMP: concentration dependence.

1. Patch-clamp recordings of single cyclic GMP-activated channels from toad rod photoreceptors were made in inside-out membrane patches containing only one such channel. Patches were obtained from the inner segment, where the density of cyclic GMP-activated channels is lower than in the outer segment, making one-channel patches possible. The dependence of channel gating on cyclic GMP concentration ([cyclic GMP]) was studied. At low [cyclic GMP] (5-10 microM), channel openings were infrequent and occurred as bursts of rapid opening and closing. As [cyclic GMP] was increased, bursts became more frequent, until at 1 mM the activity fused into long bouts of rapid flicker between open and closed states. 2. The duration of brief openings and closings (flicker) within bursts was not affected by [cyclic GMP]. This suggests that the rapid flicker within bursts results from an intrinsic channel property not associated with agonist-induced receptor activation. 3. At 10 microM-cyclic GMP, the distribution of closed times was fitted by a sum of three exponential components. The briefest, with time constant averaging 0.29 ms, corresponded to the brief closings within bursts, while the two longer components, with time constants averaging 3.5 and 32 ms, corresponded to much longer closings between bursts. At 0.5 or 1 mM-cyclic GMP (saturation), the longer components disappeared, and the distribution of closed times was fitted by a single-exponential equation with the same time constant as the briefest component observed at lower concentrations. 4. Because the channel continued to flicker even at high [cyclic GMP], the maximal probability of being in the open state (Po) did not approach 1.0, averaging 0.30 +/- 0.05 (N = 8). The relation between Po and [cyclic GMP] was fitted by the Hill equation with an exponent of 3, suggesting that binding of cyclic GMP to multiple sites is required to open the channel.

Action Potentials↗
PubMed1988

Mortality of workers at acetylene production plants.

To reduce the risk of explosion oxyacetylene cylinders are filled with a spongy mass, acetone is added to saturate the mass, and acetylene is pumped into the cylinder. The first cylinders manufactured before 1936 used a kapok filling topped off with about 16 oz of crocidolite asbestos, with a metal gauze thimble inserted to reduce risk of flash back. Cylinders must be examined annually. The use of crocidolite ceased in 1972 and other fillings have been adopted since 1970; kapok cylinders now constitute less than 5% of the total stock. To assess possible hazards, a mortality study of workers first employed between 1935 and 1975 and followed up to December 1984 was undertaken. Simulation tests showed low concentrations of asbestos in the air even in the earliest period. The population studied consisted of 370 workers at the Bilston plant in the West Midlands, 611 at the 14 other plants in England and Wales, and 120 in Scotland. No deaths occurred from mesothelial tumours but there was an excess of deaths from cancer, particularly lung cancer, cancer of the stomach, and cancer of the pancreas, the latter accounting for eight deaths. Risks appeared to be concentrated at the Bilston plant. The importance of these findings is discussed.

Acetylene↗
PubMed1988

Regional distribution of cGMP-activated ion channels in the plasma membrane of the rod photoreceptor.

In patch-clamp recordings from excised membrane patches, the distribution of cGMP-activated channels in the plasma membrane of the rod photoreceptor was examined. These channels have been shown to be the light-sensitive channels that carry the inward dark current in the rod outer segment, where phototransduction occurs (Matthews, 1987); thus, they are centrally involved in photoreceptor transduction. In the outer segment, cGMP-activated channels were present at high density. In the inner segment, cGMP-activated channels were also present, but their density was much lower than in the outer segment. Calcium-activated potassium channels had the opposite distribution, with a higher density in the inner segment. The results suggest that there is a barrier preventing the unrestricted spread of membrane proteins between the inner and outer segments.

Animals↗
PubMed1988

The prediction of habitual alcohol use from alcohol related expectancies and personality.

Two studies testing social learning theory predictions of habitual alcohol use in college students are reported. Study 1 (N = 96) investigated alcohol related expectancies and social desirability as predictors of habitual alcohol use. Higher habitual alcohol use was correlated with higher expected dominance, but this correlation was not modified by social desirability or subject sex. Study 2 (N = 88) tested effects of personality traits on habitual alcohol use. Habitual alcohol use was positively correlated with EPI extraversion. Examination of extraversion sub-factors suggests that impulsivity and sociability independently predict drinking. The data indicate the strengths and limitations of alcohol related expectancy as an explanatory construct.

Adolescent↗
PubMed1987

Single-channel recordings demonstrate that cGMP opens the light-sensitive ion channel of the rod photoreceptor.

Patch-clamp recordings were made from outer segments of single dark-adapted rod photoreceptors from toad retina. When patch pipettes were filled with a solution free of divalent cations, inward current through individual light-sensitive ion channels was sufficiently large to allow single-channel recording. Channel activity was suppressed by illumination within the normal response range of the dark-adapted rod. When illumination was restricted to a portion of the outer segment, the effect of light on channel activity was spatially localized to the illuminated region. Hyperpolarization of the recorded patch did not reduce the frequency of channel opening, indicating that the suppression of channel activity by light was due to illumination itself and not to light-induced hyperpolarization of the rod. After recording single light-sensitive channel activity in the intact cell, the patch of membrane was detached to form an excised, inside-out patch. Cyclic GMP applied to the intracellular face of the excised patch then opened a channel that appeared to be the same as the light-sensitive channel recorded earlier from the same membrane in the intact, functioning rod. This provides direct evidence that cyclic GMP acts as an internal transmitter that opens the light-sensitive channel of the vertebrate photoreceptor.

Animals↗
PubMed1987

Properties of ion channels closed by light and opened by guanosine 3',5'-cyclic monophosphate in toad retinal rods.

1. In patch-clamp recordings from outer segments of dark-adapted rod photoreceptors, single-channel recordings were obtained from the light-sensitive conductance when divalent cations were omitted from the pipette solution bathing the extracellular face of the recorded patch of membrane. 2. Activity of the light-sensitive channel was suppressed by light within the normal response range of the dark-adapted rod. During dim, steady illumination, the rate of opening of the channel fluctuated dramatically, as expected qualitatively from statistical fluctuations in the number of photoisomerizations occurring within the effective collecting area of the recorded patch. 3. The light-sensitive channel flickered rapidly in the open state, so that individual events appeared as a burst of openings and closings. The average duration of a burst was 0.78 +/- 0.03 ms (mean +/- S.E.). The average duration of an individual opening was 0.18 +/- 0.008 ms. The average closed duration within a burst was 0.37 +/- 0.02 ms. 4. Hyperpolarization of the recorded patch had no effect on average burst or open duration, although opening frequency increased slightly (+18.6 +/- 4.9%; n = 13; mean +/- S.E.). Average single-channel current increased linearly with hyperpolarization, giving an estimated single-channel conductance of 20.5 +/- 1.1 pS. By extrapolation of the relation between channel current and hyperpolarization, the dark driving force was estimated to be about 48 mV. 5. In addition to reducing the rate of channel events, dim non-saturating light also reduced the average duration of a burst of openings and the average duration of openings within a burst. 6. About 50% of cell-attached patches showed no channel activity in darkness. Light-suppressable channel activity could be induced in these silent patches by perfusing the outer segment with low-Ca2+ Ringer solution. Similarly, activity could be increased dramatically by low-Ca2+ Ringer solution in patches that did show channel activity in the dark. From the maximal channel activity observed during low-Ca2+ perfusion, the lower limit for the number of channels per patch was 20-70, corresponding to an estimated channel density of 100-350 channels micron-2. 7. After recording light-sensitive channel activity in the intact rod, the patch of membrane was excised, exposing the intracellular membrane face. Application of guanosine 3',5'-cyclic monophosphate (cyclic GMP) to the intracellular face activated channels (Haynes, Kay & Yau, 1986; Zimmerman & Baylor, 1986; Matthews, 1986d, 1987) whose properties could then be compared directly with the light-sensitive channels recorded earlier in the same patch of membrane.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Spread of the light response along the rod outer segment: an estimate from patch-clamp recordings.

Longitudinal spread of the light response was studied using cell-attached patch-clamp recordings from the outer segments of isolated rod photoreceptors from toad retina. The effective photon-collecting area over which photoisomerizations influenced the membrane current through the recorded patch of membrane was determined by measuring the probability of a detectable response as a function of flash photon density (i.e. a "frequency-of-seeing" experiment). The effective collecting area averaged 0.40 micron2, which corresponds to a total sampling length of approximately 1 micron for the patch electrode.

Animals↗
PubMed1986

Comparison of the light-sensitive and cyclic GMP-sensitive conductances of the rod photoreceptor: noise characteristics.

Patch-clamp recordings were made from outer segments of single rod photoreceptors isolated from toad retina. Cyclic GMP (cGMP) and its hydrolysis-resistant analog, 8-bromo-cGMP, increased the conductance of excised membrane patches when applied to the intracellular face of the membrane but not when applied to the extracellular face. The rectification properties of the cGMP-dependent conductance depended on the concentration of divalent cations bathing the intra- and extracellular membrane faces. Current flow was favored from the side of the membrane, either internal or external, that was exposed to bathing fluid free of divalent cations. The power spectral density of cGMP-induced noise was fitted by a sum of 2 Lorentzian components, with corner frequencies differing approximately 15-fold on average. This suggests that channel gating is controlled by 2 kinetic components. To compare the cGMP-sensitive conductance with the light-sensitive conductance of the rod, cell-attached patch-clamp recordings were made from intact, dark-adapted rods, and noise arising from the light-sensitive conductance was analyzed. The power spectrum of the light-sensitive noise also exhibited 2 Lorentzian components similar to those of the cGMP-sensitive conductance in excised patches. These results are consistent with the idea that cGMP opens the light-sensitive channel of the rod outer segment.

Animals↗
PubMed1986

Australian National Health and Medical Research Council dietary salt study in mild hypertension.

Two-hundred-and-twelve untreated subjects (mean age 52.3 +/- 0.8 years; 181 males and 31 females) with a diastolic blood pressure between 90 and 100 mmHg were recruited to the study. Subjects were seen fortnightly and, after 4 pre-diet visits, were randomized into a normal diet group (A, 55 subjects), a high-potassium diet group (B, 52 subjects receiving greater than 100 mmol K+/day) a reduced-sodium diet group (C, 52 subjects receiving 50-75 mmol Na+/day) or a high-potassium and low-sodium diet group (D, 53 subjects receiving same Na+ and K+ as groups B and C). Two-hundred subjects completed the diet phase of 12 weeks. Urine sodium fell to 86 +/- 7 mmol/day in group C and 73 +/- 6 mmol/day in group D, while daily potassium excretion rose to 96 +/- 5 mmol in group B and 87 +/- 4 mmol in group C. Systolic and diastolic blood pressure fell by 3.8 +/- 1.0 and 1.6 +/- 0.6 mmHg respectively in the normal diet group. The falls in systolic and diastolic blood pressures (mmHg) in the diet phase were 7.7 +/- 1.1 and 4.7 +/- 0.7 (B), 8.9 +/- 1.0 and 5.8 +/- 0.6 (C) and 7.9 +/- 0.9 and 4.2 +/- 0.7 (D). These falls were all greater than those in the control group on an intention-to-treat analysis (P less than 0.005) but did not differ from each other. Factorial analysis confirmed that the falls in pressure attributable to the low-sodium diet and high-potassium diet were not additive.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1985

Electroencephalographic sleep of younger depressives. Comparison with normals.

The electroencephalographic sleep of younger depressives (aged 20 to 44 years) was compared with that of an age-matched group of normals. The patients demonstrated many of the typical sleep changes reported for older depressed populations: shortened rapid-eye-movement (REM) latency; REM sleep activity alterations, with a shift to the early portion of the night (first REM period); reduced delta sleep; and sleep efficiency reductions marked by sleep-onset difficulties. The traditional scoring procedures were supplemented by automated REM and delta-sleep analyses that provided more precise delineation of these differences between patients and normals, particularly the distributions of REM activity and delta-wave patterning.

Adult↗
PubMed1985

Spatial spread of light-induced sensitization in rod photoreceptors exposed to low external calcium.

Light sensitizes rods that have been desensitized by exposure to low external calcium. Yoshikami and Hagins [Biophys. Soc. Abstr. 15, 169a (1975)] suggested that desensitization in low external calcium results from exposure of intracellular calcium binding sites subsequent to depletion of internal calcium, and that background light sensitizes in this situation by releasing calcium to occupy those binding sites. In this view, it might be expected that light-induced sensitization would be spatially restricted to the illuminated region of the outer segment. However, in the present experiments, background illumination at one end of the outer segment potentiated responses to test flashes at the other end; resensitization was global rather than local. Patch-clamp recordings from the outer segment showed that the spread of internal transmitter was longitudinally restricted. Therefore, the sensitizing effect of background light is apparently not mediated via the internal transmitter, as required in the calcium-depletion explanation described above.

Animals↗
PubMed1985

Membrane current noise in toad retinal rods exposed to low external calcium.

Outer segment membrane current of single rod photoreceptors from toad retina was recorded with a suction electrode, and extracellular calcium concentration was manipulated by transferring the recorded cell from one pool of saline to another or by locally perfusing the outer segment. The large increase in dark current that resulted from exposure to low-calcium saline was accompanied by an increase in dark noise in the band 1-800 Hz. This noise was suppressed by bright light, and its power spectrum could be described by a single Lorentzian equation with average corner frequency of 40.1 +/- 9.5 Hz (mean +/- S.D., n = 11). In low-calcium saline, saturating flash responses were often followed by a transient increase in the dark current lasting 30-100 s. During this rebound period of increased dark current, increased dark noise similar to that described in 2 was observed. The power spectrum of this noise was also fitted by a single Lorentzian equation, with corner frequency averaging 29.7 +/- 6.6 Hz (mean +/- S.D., n = 27). To examine the possible role of intracellular voltage fluctuations in generating the noise, suction electrodes were filled with calcium-free saline and recordings were made from outer segments of rods attached to pieces of retina. In this recording configuration, the electrical coupling among the rods in the piece should attenuate voltage fluctuations associated with the post-light rebound period of increased dark current. In this situation, the rebound increase in dark current was still observed, but the noise was reduced or absent. Using the same recording configuration, isolated rods showed pronounced noise during the rebound. The result in 4 suggests that the noise resulted from fluctuations in intracellular voltage, not directly from fluctuations in the light-sensitive channels. In this view, the corner frequency of the noise power spectrum probably reflects the membrane time constant of the isolated rod.

Action Potentials↗
PubMed1984

Photocurrents of single retinal rods from Rana pipiens tadpoles.

Outer segment membrane current was recorded from single rod photoreceptors of Taylor-Kollros State III and Stage XXIII tadpoles. Response-intensity relations and kinetics of the photocurrent were similar to those of audit amphibian photoreceptors, suggesting that phototransduction is quantitatively similar in developing rods and adult rods. Maximum response amplitude was about 1/3 that of adult rods, probably because of the shorter length of the outer segment in tadpoles (20 vs 50 micrometers).

Animals↗
PubMed1984

Application of automated REM and slow wave sleep analysis: I. Normal and depressed subjects.

Computerized analysis of rapid eye movement (REM) and delta electroencephalographic (EEG) sleep patterns in normal and depressed subjects offers opportunities to examine sleep more precisely than previously possible. In the present study, automated REM analyses demonstrated good reliability with traditional manual procedures in both normal and depressed subjects. However, automated delta analyses correlated well with traditional scoring in normal subjects, but not in depressed patients. These findings suggest the use of automated delta techniques similar to those employed in this report or spectral analytic techniques in the following types of studies: specificity of delta sleep in various psychiatric syndromes, changes in delta sleep produced by the administration of psychotropic agents, relationships between delta sleep and sleep-related neuro-endocrine patterns, and, finally, relationships between delta sleep patterns and other biological rhythms such as activity and temperature.

Adult↗
PubMed1984

Application of automated REM and slow wave sleep analysis: II. Testing the assumptions of the two-process model of sleep regulation in normal and depressed subjects.

Abnormalities in a two-process model of sleep regulation (a sleep-dependent process, termed Process S, and a sleep-independent circadian process, termed Process C) have been proposed to account for sleep abnormalities in depressive states. The major tenets of the two-process model of sleep regulation as applied to depression are: the level of process S, as reflected by the electroencephalographic (EEG) slow-wave activity, corresponds to the sleep-dependent facet of sleep propensity; the pathognomonic changes of sleep in depressives are a consequence of a deficiency in the build-up of process S. The application of automated rapid eye movement (REM) and delta wave analyses in normal subjects and younger depressed patients supports the model to some extent: The time spent asleep is positively correlated with total delta waves (normals and depressives) and average delta waves (depressives); delta sleep is lower in depressives than in normals; the average delta wave count is significantly reduced in younger depressives over the total night and in non-REM period 1. The model also postulates that measures of phasic REM activity are inversely related to process S, suggesting that process S can be regarded as exerting an inhibitory influence on phasic REM activity.

Adult↗
PubMed1984

All-night spectral analysis of the sleep EEG in untreated depressives and normal controls.

Sleep was recorded in nine drug-free depressive patients and nine age- and sex-matched normal control subjects. All-night spectral analysis of the sleep electroencephalogram (EEG) showed a significantly reduced power density in the 0.25-2.50 Hz band in the depressive group. Power density values integrated over the entire frequency range (0.25-25.0 Hz) exhibited for both groups a decreasing trend over the first three non-REM/REM sleep cycles. In each cycle depressives had lower values than controls. The results are consistent with hypothesis that the build-up of a sleep-dependent process is deficient in the sleep regulation of depressive patients.

Adult↗