Biomedical subjects

A Stockman

Publications and source records attributed to A Stockman.

At least 37 records · Page 2Linked to original sources

PubMed1994

Spatial relations of flicker signals in the two rod pathways in man.

1. Flicker signals originating from the human rod photoreceptors seem to have access to two retinal pathways: one slow and sensitive, the other fast and insensitive. The phase lag between signals in the two pathways grows monotonically with frequency, reaching 180 deg near 15 Hz. 2. At 15 Hz, destructive interference between the slow and the fast signals can cause two related phenomena: (i) a suprathreshold intensity region--the perceptual null--within which the perception of flicker vanishes, and (ii) a double branching of the 15 Hz rod-detected flicker threshold versus intensity (TVI) curve. 3. Here we investigate the effect of changing target size on these phenomena in normal human observers. We find that the double-branched flicker TVI curve and the perceptual null are found for all targets larger than 2 deg in diameter. For smaller diameter targets, however, neither the lower branch of the double-branched flicker TVI curve nor the null are found. 4. While this might suggest that the slow rod signals are selectively disadvantaged by the use of small targets, phase measurements relative to a cone standard reveal that the slow signals are always present. For targets < or = 2 deg in diameter, however, they remain below detection threshold because of destructive interference with the fast rod signals. Thus, for small targets, the perceptual null is not absent, but has merged with (and therefore obliterated) the lower branch of the double-branched flicker TVI function. 5. This situation could arise if decreasing the target size causes a parallel reduction in the sensitivities of both pathways, rather than a selective reduction in the sensitivity of either one. Our findings are therefore consistent with a model in which the large-scale spatial organization of the two rod pathways is roughly similar.

Electrophysiology↗

PubMed1994

Specificity of antibodies to type II collagen in early rheumatoid arthritis.

OBJECTIVE: To analyze the antibody response to native type II collagen in early rheumatoid arthritis (RA), examining the immunoglobulin isotypes, and polypeptide epitopes recognized, in patients followed over a 2-year period from within 6 months of the first occurrence of symptoms. METHODS: Sera from 16 patients were studied, of whom 10 had antibodies to native type II collagen and 6 did not. The clinical and laboratory assessment, carried out initially and at 6 monthly intervals included the number of 1958 ARA criteria fulfilled, Ritchie index, erythrocyte sedimentation rate, rheumatoid factor and radiological assessment. An ELISA was used to measure IgG, IgA and IgM antibodies, and immunoblotting to identify the number and location of epitopes, using polypeptides prepared by cyanogen bromide digestion of human type II collagen. RESULTS: Antibodies to type II collagen were present in all sequential serum samples for the 10 antibody positive patients. None of the 6 patients who initially lacked antibodies developed them. The antibodies were of IgG isotype in 9, of IgA isotype in 8, and of IgM isotype exclusively in one. At the initial clinical assessment patients with antibodies to collagen were indistinguishable from those without. At 12 and 24 months patients with antibodies fulfilled significantly more ARA criteria than antibody negative patients. The patterns of antibody reactivity to collagen polypeptides by immunoblotting were constant over time but differed from patient to patient. CONCLUSION: The presence of an established and persisting IgG antibody response to type II collagen in early RA before cartilage destruction is evident points to a subset of RA, perhaps equivalent to the collagen induced model in animals, in which this immune response is intrinsic to pathogenesis.

Adult↗

PubMed1993

The spectral properties of the two rod pathways.

Psychophysical and electroretinographic observations in normal and achromat observers suggest that rod flicker signals have access to at least two retinal pathways: one (pi 0), slow and sensitive, predominating at scotopic luminance levels; the other (pi'0), fast and insensitive, predominating at mesopic ones. We have measured steady-state flicker detection sensitivities on background fields ranging from 430 to 640 nm in normal observers. Our results suggest that cone signals can reduce the sensitivity of pi'0, but have comparatively little effect on pi 0. The pi'0 field sensitivities derived from these measurements have been fitted with linear combinations of the scotopic luminosity function, V' lambda, the M-cone spectral sensitivity function, M lambda, and the L-cone function, L lambda. These fits demonstrate a clear cone influence on pi'0, but they cannot tell us unequivocally whether the influence is from the M-cones, from the L-cones or from both. Accordingly, we made similar measurements in dichromats, who lack one of the two longer wavelength cone types. These measurements revealed an L-cone influence on pi'0 in the deuteranope and an M-cone influence in the protanope. This suggests that both cone types can affect the sensitivity of pi'0. The finding that the steady-state cone signals reduce the sensitivity of pi'0 but have little effect on pi 0 could suggest that pi'0 signals travel through a faster cone pathway (with its own gain control at which both rod and cone signals can reduce rod threshold), while pi 0 signals travel through a separate rod pathway. However, it could simply reflect the fact that pi'0 predominates at higher luminances than pi 0 where the cone excitation level is inevitably greater. To examine the influence of the cones on pi 0 more closely, we: (i) produced transient cone excitation by alternating rod-equated 480 and 679 nm fields; and (ii) extended our steady-state measurements to include deep-red backgrounds of 650 and 680 nm. Both experiments revealed a small, but measurable influence of the cones on pi 0.

Color Vision Defects↗

PubMed1993

Temporal and spatial summation in the human rod visual system.

1. Absolute and increment thresholds were measured in a retinal region 12 deg temporal from the fovea with 520 nm targets of varying size and duration. Measurements were made under rod-isolation conditions in two normal observers and in a typical, complete achromat observer who has no cone-mediated vision. The purpose of these experiments was to determine how the temporal and spatial summation of rod-mediated vision changes with light adaptation. 2. The absolute threshold and the rise in increment threshold with background intensity depend upon target size and duration, but the psychophysically estimated dark light of the eye (the hypothetical light assumed to be equivalent to photoreceptor noise) does not. 3. The rise in increment threshold for tiny (10 min of arc), brief (10 ms) targets approaches the de Vries-Rose square-root law, varying according to the quantal fluctuations of the background light. The slope of the rod increment threshold versus background intensity (TVI) curves in logarithmic co-ordinates is about 0.56 +/- 0.04 (when cones are not influencing rod field adaptation). For large (6 deg) and long (200 ms) targets, a maximum slope of about 0.77 +/- 0.03 is attained. 4. The steeper slopes of the rod-detected TVI curves for large, long targets implies some reduction in temporal or spatial summation. In fact, the change in summation area is much more critical: under conditions where only the rod system is active the TVI curve slope is independent of target duration, suggesting that temporal summation is practically independent of background intensity. 5. The rise in threshold also depends on the wavelength of the background field in the normal observer but not in the achromat, confirming reports that the field adaptation of the rods is not independent of the quantal absorptions in the cones. The cone influence is most conspicuous on long-wavelength backgrounds and is found for all target sizes and durations, but is greater for large and long targets than for the other conditions.

Adult↗

PubMed1993

Faster than the eye can see: blue cones respond to rapid flicker.

Flickering lights that are detected by the blue cones of the human visual system fuse to yield a steady sensation at much lower rates of flicker than do lights that are detected by the red or green cones. Yet, although blue-cone-detected lights flickering at 30-40 Hz appear to be steady, they are still able to interact with red- or green-cone-detected flickering lights to produce clearly detectable beats in the form of an amplitude modulation of the red- or green-cone flicker. Thus the blue cones produce a viable high-frequency flicker signal, as do the red and green cones, but one that is normally lost before it reaches sensation. The temporal-frequency response for the blue-cone beat interaction is similar in shape to the temporal-frequency response for directly detected red- or green-cone flicker. When measured through the same pathway (which we identify as the luminance pathway, since it is able to transmit high-frequency flicker), the response of the blue cones seems to be as fast as that of the other cones.

Color Perception↗

PubMed1993

Isolation of the middle- and long-wavelength-sensitive cones in normal trichromats.

Spectral sensitivity in the red-green spectral range typically reflects the joint influence of the middle-wavelength-sensitive cones (the M or green cones) and long-wavelength-sensitive cones (the L or red cones). The balance of M- and L-cone influence can be altered by presenting the test lights superimposed upon steady background fields of long or short wavelength. We find that presenting test stimuli just after an abrupt exchange between two colored backgrounds permits an easier and closer approach to cone isolation than presenting them either on a steady background or following an intense bleach. Background exchange drives the flicker detection or flicker photometric spectral sensitivities measured at 17 Hz to a limiting condition at lower intensities than do steady backgrounds. This condition is consistent with either M- or L-cone isolation. Steady backgrounds do not produce complete cone isolation: even on backgrounds that push spectral sensitivity closest to M or L, there are substantial phase differences between flickering lights of different color. In contrast, no phase differences remain following background exchange. The improvement in cone isolation produced by the exchange procedure is not confined to flicker measurements: the spectral range over which subjects are temporarily monochromatic is more extended following background exchange than on steady fields.

Color Perception↗

PubMed1993

Spectral sensitivities of the human cones.

Transient chromatic adaptation produced by an abrupt change of background color permits an easier and closer approach to cone isolation than does steady-state adaptation. Using this technique, we measured middle-wave-sensitive (M)-cone spectral sensitivities in 11 normals and 2 protanopes and long-wavelength-sensitive (L-) cone spectral sensitivities in 12 normals and 4 deuteranopes. Although there is great individual variation in the adapting intensity required for effective isolation, there is little variation in the shape of the M- and L-cone spectral-sensitivity functions across subjects. At middle and long wavelengths, our mean spectral sensitivities agree extremely well with dichromatic spectral sensitivities and with the M- and L-cone fundamentals of Smith and Pokorny [Vision Res. 15, 161 (1975)] and of Vos and Walraven [Vision Res. 11, 799 (1971)], both of which are based on the CIE (Judd-revised) 2 degrees color-matching functions (CMF's). But the agreement with the M-cone fundamentals of Estévez [Ph.D. dissertation, Amsterdam University (1979)] and of Vos et al. [Vision Res. 30, 936 (1990)], which are based on the Stiles-Burch 2 degrees CMF's, is poor. Using our spectral-sensitivity data, tritanopic color-matching data, and Stile's pi 3, we derive new sets of cone fundamentals. The consistency of the proposed fundamentals based on either the Stiles-Burch 2 degrees CMF's or the CIE 10 degrees large-field CMF's with each other, with protanopic and deuteranopic spectral sensitivities, with tritanopic color-matching data, and with short-wavelength-sensitive (S-) cone spectral-sensitivity data suggests that they are to be preferred over fundamentals based on the CIE 2 degrees CMF's.

Color Perception↗

PubMed1992

The field adaptation of the human rod visual system.

1. Incremental thresholds were measured in a retinal region 12 deg temporal from the fovea with a target of 200 ms in duration and 6 deg in diameter superimposed on background fields of various intensities and wavelengths. Measurements were made under rod-isolation conditions in five normal observers and in a typical, complete achromat observer who had no cone function. 2. The rise in threshold with background intensity changes with background wavelength in the normal trichromat observers. On 450, 520 and 560 nm backgrounds the average slope in logarithmic co-ordinates (0.78 +/- 0.04, S.D.) is similar to that found for the achromat--whose slope is independent of background wavelength (0.79 +/- 0.03)--but on a 640 nm background it more nearly approaches Weber's law (0.91 +/- 0.02). This indicates that the sensitivity of the rods to an incremental target is not determined by quantal absorptions in the rods alone but by quantal absorptions in both the rods and the cones. 3. Rod incremental thresholds were also measured in various colour-blind observers lacking one or more of the cone classes: a blue-cone monochromat, four deuteranopes and a protanope. For the blue-cone monochromat, like the achromat, the slope of the increment threshold curve is constant with background wavelength. For the deuteranopes and the protanope, like the normal, the slope increases with wavelength. The protanope, however, shows a smaller increase in slope, consistent with the lower sensitivity of his cones to long-wavelength light. 4. The dependence of the field adaptation of the rods on the cones was confirmed by field-mixture experiments, in which the incremental threshold was measured against bichromatic backgrounds, and in silent substitution experiments, in which backgrounds equated for their effects on either the cones or the rods but not both were instantaneously substituted for one another.

Adaptation, Ocular↗

PubMed1991

The temporal properties of the human short-wave photoreceptors and their associated pathways.

Flicker modulation sensitivity measurements made on high intensity orange steady backgrounds indicate that signals from short-wavelength sensitive cones (S-cones) have access to two pathways. At low S-cone adaptation levels the frequency response falls quickly with increasing frequency, but at higher adaptation levels it extends to much higher frequencies. At these higher S-cone adaptation levels, the following procedures can selectively expose either a process sensitive to low frequencies or one more sensitive to higher frequencies: (1) at high flicker frequencies, the S-cone signal can be nulled by a long-wavelength sensitive cone (L-cone) signal of suitable amplitude and phase, but at low frequencies a residual flicker persists; the modulation sensitivity for the residual flicker is lowpass in shape with a rapid decline in sensitivity with increasing flicker frequency; (2) sensitivity to flicker in the presence of a 17 Hz S- or L-cone mask is also lowpass with a similarly steep loss of high frequency sensitivity; yet (3) sensitivity to flicker during transient stimulation of the S-cones at 0.5 Hz is comparatively wideband (and slightly bandpass) in shape. The S-cone signal produced by the high frequency process is almost as well-maintained towards high frequencies as M- and L-cone signals. Furthermore, it is capable of participating in flicker photometric nulls with M- and L-cone signals. At low frequencies, however, when the low frequency S-cone signal is also present, satisfactory nulls can not be found. From these and phenomenological considerations, we identify the low and high frequency S-cone processes as S-cone inputs to the chromatic and luminance pathways, respectively. The phase adjustments needed to optimize flicker photometric nulls reveal that the S-cone input to the luminance pathway is actually inverted, but this is demonstrable only at relatively low frequencies: at medium or high frequencies the S-cone influence can be synergistic with that of the other cone types because of a delay in the transmission of S-cone signals.

Adaptation, Ocular↗

PubMed1991

Anti-neutrophil cytoplasm antibodies in rheumatoid arthritis.

Anti-neutrophil cytoplasm antibodies (ANCA) occur occasionally in rheumatoid arthritis (RA), but their incidence and clinical significance have been unclear. In this study we have investigated 58 patients with RA. In 22 patients the disease was inactive and the remaining 36 with active disease were further subdivided into those without clinical evidence of vasculitis (26), those with cutaneous vasculitis (8) and those with systemic vasculitis (2). ANCA were demonstrated by indirect immunofluorescence in 10 of the 58 patients (17%). While both perinuclear (pANCA) and cytoplasmic (cANCA) staining were detected, pANCA were more common (70%). Neutrophil-specific anti-nuclear antibodies (ANNA) were demonstrated in a further eight sera (14%) and ANA were detected on Hep-2 cells in 30 of the 58 sera (52%). ELISAs for the detection of anti-myeloperoxidase and anti-elastase antibodies were then established. Five sera with pANCA and five that contained ANNA were negative for both anti-myeloperoxidase and anti-elastase antibodies, suggesting other as yet unidentified cytoplasmic antigens as the target molecules. However, anti-myeloperoxidase or anti-elastase antibodies were found in four sera that had homogeneous or speckled ANA on both Hep-2 cells and neutrophils. One serum contained both antibodies. The presence of ANCA detected by indirect immunofluorescence or of anti-myeloperoxidase or anti-elastase antibodies in these patients with RA was not associated with disease activity nor with the demonstration of cutaneous vasculitis or renal disease (P NS). A possible association with systemic vasculitis remains to be confirmed. There is an incomplete correlation between indirect immunofluorescence patterns and antibody specificity in ELISA systems.

Antibodies, Antinuclear↗

PubMed1991

Slow and fast pathways in the human rod visual system: electrophysiology and psychophysics.

Under most conditions, increasing the intensity of a flickering light makes the flicker more conspicuous. For a light flickering at 15 times per second, however, increasing the intensity can cause the flicker to disappear before reappearing again at higher intensities [Vision Res. 29, 1539 (1989)]. This flicker disappearance or null is also evident in human electrophysiological recordings at the same intensity levels. These results point to a duality within the rod visual pathway, in which flicker signals travel through a slow and a fast pathway and then recombine at a later stage. At 15 Hz the slow rod flicker signals are delayed by half a cycle relative to the fast signals. Thus, when the two signals are recombined, they destructively interfere and diminish the perception of flicker. The dual-pathway interpretation is supported by both electroretinographic and psychophysical evidence showing a phase difference of half a cycle between 15-Hz rod signals just below and just above the null region. These effects are apparent not only in the normal observer but also in an achromat observer who lacks functioning cone vision.

Electrophysiology↗

PubMed1991

Relationship of progression of radiographic changes in hands and wrists, clinical features and HLA-DR antigens in rheumatoid arthritis.

One hundred and twelve hospital based outpatients with rheumatoid arthritis (mean duration +/- standard error, 10.7 +/- 0.9 years) were studied for radiological progression of the hands and wrists over a mean period of 26.5 +/- 0.5 months. The majority were taking slow acting antirheumatic drugs (SAARD). The rate of radiographic progression was positively and independently associated with the female sex (p less than 0.01), erythrocyte sedimentation rate (ESR, p less than 0.05) and HLA-DR1 (p less than 0.05). There was a negative association with HLA-DR4 (p less than 0.05) but this was no longer significant after adjusting for ESR. There was no relationship between the rate of radiological progression and the presence of rheumatoid factor, rheumatoid nodules and duration of treatment with SAARD.

Arthritis, Rheumatoid↗

PubMed1989

The incremental threshold of the rod visual system and Weber's law.

The incremental threshold of the isolated rod visual system is believed, under certain conditions, to obey Weber's law (that is, to increase in direct proportion to the intensity of the background). This relation was tested at several background wavelengths, over an intensity range for which the target was seen only by the rods. Although the slope on long-wavelength background approximates unity (that is, Weber's law on log-log coordinates), it averages less than 0.8 on short- and middle-wavelength backgrounds. This is the same value as that found for the thresholds of a typical, complete achromat--who lacks cone vision--regardless of background wavelength. These results force the conclusion that Weber's law for incremental threshold detection is achieved not by the rods alone but only by the rods acting together with the cones.

Dark Adaptation↗

PubMed1989

Activity of rheumatoid arthritis and levels of collagen antibodies: a prospective study.

Thirty-seven patients with classical or definite rheumatoid arthritis (RA) were studied prospectively over a period of 12 months to assess whether there was a relationship between disease activity and raised levels of antibodies to native or denatured type II collagen. Nineteen patients had inactive RA according to ARA criteria for disease remission and 18 had active RA throughout the study. At the beginning of the study the levels of collagen antibodies were comparable in each group. After 1 year, antibodies to denatured type II collagen in patients with inactive RA had declined to significantly lower levels whereas in patients with active RA the levels of antibodies fluctuated during the period of study and were not significantly different at the end. There was no relationship between levels of antibodies to type II collagen and any specific index of disease activity, severity of X-ray changes in the hands and feet, or progression over 1 year in X-ray changes. The finding of a decline in levels of antibodies to denatured type II collagen in inactive RA suggests that the anticollagen response is an integral component of the rheumatoid process and could have a primary or secondary role in pathogenesis.

Adult↗

PubMed1989

Rod flicker perception: scotopic duality, phase lags and destructive interference.

Rod vision has a duality of organization: at mesopic luminances rod signals have access to a slow, sensitive pathway (which we refer to, following Stiles, as pi 0) and a fast, insensitive pathway (pi' 0). The phase lag between the two rod signals increases with frequency until at 15-Hz the rod signals transmitted through the two pathways emerge out-of-phase, so that destructive interference produces a nulling of the apparent flicker. Relative to the cones, the phase lag of pi' 0 is roughly half that of pi 0. Thus at 15-Hz pi' 0 signals can be out-of-phase with cone signals, so that the signals from the slower pathway, pi 0, are actually in phase with cone signals. We have investigated the frequency response, adaptation behavior and phase characteristics of the two rod processes. The slower process, pi 0 is more sensitive than pi' 0, and dominates from absolute threshold up to low mesopic levels. The adaptation of pi 0 seems not to be associated with a change in time constant, but rather with simple response compression or sensitivity scaling. The time constant of pi' 0, however, does change with adaptation. There are large differences in the way that light adaptation changes the sensitivity of the two processes: signals from pi'0 may evade part of the postreceptoral sensitivity regulating mechanism normally associated with rod vision. The ability of signals from pi 0 and pi' 0 to reinforce or cancel each other, however, suggests that they are later reunited in a common pathway.

Dark Adaptation↗

PubMed1988

High-affinity interleukin-2 receptors on blood lymphocytes are decreased during active rheumatoid arthritis.

The expression of receptors for interleukin-2 (IL-2R) was examined in patients with active or inactive rheumatoid arthritis (RA) and in control subjects. Unstimulated blood lymphocytes from patients with active RA had increased levels of total IL-2R, as measured by Tac-positive cells, compared with the levels found in the other 2 groups. Mitogen-stimulated cells from patients with active RA expressed less IL-2R per cell, but the most striking feature was the failure to express high-affinity IL-2R. These changes could reflect persistent antigenic stimulation and explain the defective cell-mediated immunity in RA patients.

Adult↗

PubMed1987

Transient tritanopia of a second kind.

Using a psychophysical method that allows the tracking of very rapid changes in sensitivity, we demonstrate an anomaly in the time-course of light adaptation for the short-wave mechanism: after the onset of a yellow (581 nm) field of approximately 10(5.3) td the threshold for short-wave targets does not recover monotonically but continues to rise for several seconds before falling to its equilibrium value. The phenomenon is absent when the adapting field has a wavelength of 511 nm and has been adjusted to give a similar equilibrium value for the short-wave threshold.

Adaptation, Ocular↗

PubMed1987

Improvement in human vision under bright light: grain or gain?

1. The factor by which increment threshold changes with changing background intensity is less if the test flash is small than if it is large. This is commonly attributed to a reduction of the area over which visual signals are integrated as light adaptation increases. 2. We propose and test an alternative hypothesis that the change in slope is the result of purely local processes: if it is assumed that increasing the background intensity increases the exponent of the local response function, but does not alter the extent of spatial integration, then the threshold of the small test flash will rise more slowly than the threshold of the large test flash simply because the small test flash is of a higher intensity than the large and therefore evokes a correspondingly greater local response. 3. We measured small and large test field increment thresholds and dichoptic brightness matches as a function of background intensity. 4. The log-log slopes of the small and large field increment threshold functions differed by not more than about 20%, suggesting that even under the conventional interpretation of such data, the change of spatial integration is less than is usually supposed. 5. The intensity of a large (2.3 deg) suprathreshold test field matched to a standard in the other eye varies with increasing background intensity with the same shallow slope as the small test (2.6 min) threshold versus intensity function; this is in agreement with the predictions of the local non-linearity hypothesis and suggests that there is no substantial change in spatial integration during light adaptation.

Adaptation, Ocular↗