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Perimetry of some kind remains an important tool in the detection, diagnosis and monitoring of glaucomatous damage to the visual pathway. However, recent studies have served to reinforce the suspicion that conventional perimetry does not possess the sensitivity to detect the earliest signs of functional loss resulting from glaucoma. The relationship between differential light threshold and ganglion cell loss is extremely weak and, in the early stages of glaucoma, non-existent. Alternative, more novel perimetric techniques seem to offer promise of better detectability for early loss by claiming to tap in to one or other of the separate parallel pathways of the visual system. While some of these tests show potential for better detection and monitoring of glaucoma, the reasons why this might be so are not always clearly formulated or represented. This leads to misunderstanding of what the test actually measures and of the glaucomatous disease process itself. This paper seeks to revisit and review the theory underlying psychophysical testing of visual function related to glaucoma and stresses the importance of developing tests that are based on a firm theoretical understanding of visual function and processing in order to both detect glaucoma at an earlier stage and better understand the mechanisms of loss from the disease process.

We measured the S-cone contrast threshold for stimuli of different size modulated along the white -90 deg direction in the isoluminant plane of DKL color space. The stimuli were presented at eccentricities of 5-30 deg in the horizontal temporal retinal meridian. Ricco's area of complete spatial summation was estimated using a bilinear fit of the log threshold/log area function. Ricco's area increased towards the retinal periphery to include an increasing number of S-cones while remaining 1.6-1.8 times larger than the dendritic field area of the small bistratified and parasol retinal ganglion cells. Assuming constant coverage factor by the dendritic field, Ricco's area incorporated a constant number (three to four) of small bistratified cells. It was also found that the threshold contrast for stimuli that matched Ricco's area was constant across the studied eccentricity range, similar to previous findings for achromatic vision. Our data support the point of view that this invariance is the result of a constant number of cells involved in stimulus detection.

Psychophysical measurements using achromatic grating resolution acuity in peripheral vision show a prominent retinal asymmetry in acuity which is consistent with predicted values based on available estimates of midget ganglion cell density. Recent studies have shown that peripheral grating resolution acuity values for short-wavelength-sensitive (SWS) isolating gratings in normal observers are closely related to predicted values based on the underlying small bistratified ganglion cell density. By measuring SWS resolution acuity at different locations across the visual field, we wished to see if any significant acuity asymmetry exists for the short-wavelength system. In addition to this, we wanted to compare SWS and achromatic resolution acuity at different retinal locations of equal eccentricity. SWS and achromatic grating resolution acuity was measured in two observers at a number of different retinal meridians of 10- and 25-deg eccentricity from the fovea, and out to 35-deg eccentricity along the horizontal meridian. Achromatic resolution acuity was higher than SWS resolution acuity at all locations. At 10-deg eccentricity there was slight radial asymmetry in SWS and achromatic acuity, both displaying highest acuity along the horizontal meridian. At 25-deg eccentricity, SWS and achromatic acuity showed significant asymmetry with acuity being higher in the nasal retina compared to the temporal retina and with higher acuity in the superior retina compared to the inferior retina. At 35-deg eccentricity, the acuity asymmetry along the horizontal meridian was maintained with acuity for both significantly higher in the nasal retina. The SWS acuity changes with eccentricity and meridian were qualitatively similar to that found for achromatic acuity at the majority of retinal locations. Like achromatic acuity, SWS acuity shows significant asymmetry at different retinal locations of equal eccentricity. This suggests that both the midget and small bistratified ganglion cell population density changes significantly with retinal location and eccentricity. SWS acuity appears to change in parallel with achromatic acuity for the majority of retinal locations measured, although the amount of nasotemporal asymmetry appears to be slightly less for the SWS system at 25- and 35-deg eccentricity.

Purpose: An experimental study investigated the effects of simulated impairment of contrast sensitivity (CS) on performance and eye gaze patterns during locomotion through a library., Method: Normally sighted participants with simulated CS impairment (diffusive blur) walked two routes, one entailing limited change in direction (simple) and the other entailing several changes in direction (complex), while eye movements relative to the scene were recorded. Performance variables included walking speed in completing the route, pauses during travel, and collisions with objects on the route. For eye movements, dwell time and saccades were determined for each of three object classes: (1) objects on the route below eye level; (2) objects on the route extending above eye level; and (3) elsewhere-objects not on the route., Results: Walking speed was significantly affected by CS level and by route; pauses and collisions were rare. Dwell times and saccades suggested limited attention directed to low-level objects, except for CS impairment on the complex route. In the complex route, saccades and dwell times in the object class "elsewhere" were also reduced., Conclusions: The results for the simple route suggest ballistic strategies: the participant appraises the scene and follows a more or less predetermined path. For the complex route, CS impairment appears to adversely affect information processing and locomotion. The results have implications for the design of built environments, especially with regard to the safety of visually impaired occupants during emergency scenarios.

We wished to devise a measure of dissimilarity (D) which could predict psychophysical discrimination performance for Snellen letter pairs in peripheral vision. Threshold size for discriminating 33 pairs of Snellen letters was measured at 30 degrees eccentricity in the nasal retina for two subjects. D was computed for each pair by performing an overlap subtraction in the spatial domain, followed by a Fast Fourier Transform on this difference image, and dividing the total power in the resultant 'difference spectrum' by the sum of the powers of the individual letter spectra. A plot of D vs. psychophysical threshold letter size gave a mean correlation of R = -0.81. When D was calculated for letters that were low-pass filtered at different cut-off frequencies, the correlation with psychophysical performance was greatest when cut-off was between 1.25-1.9 cycles/letter (R = -0.85). Conversely, when the difference spectrum was high-pass filtered at different cut-off frequencies, the correlation decreased continuously as the cut-off increased. These results imply that the band of frequencies between zero and 1.25 cycles/letter are most important for letter discrimination in peripheral vision.

We studied spatial summation for S-cone ON and OFF signals as a function of retinal eccentricity in human subjects. S-cone isolation was obtained by the two-colour threshold method of Stiles, modified by adding blue light to the yellow background. Test stimuli were blue light increments or decrements within a circular area of variable size. These were presented for 100 ms at 0 to 20 deg along the horizontal temporal retinal meridian. Ricco's area of complete spatial summation was measured from the threshold vs. area curves. This was nearly constant and approximately the same for both types of stimuli within the 0-5 deg range and increased beyond this range. The decremental area increased faster, suggesting that separate mechanisms, presumably ON and OFF, integrate S-cone increments and decrements. The results appear to provide new evidence for the existence of separate S-cone ON and OFF pathways. We compare the data with known morphology of primate retina and assume that, if S-cone decrements are detected via separate OFF cells, these should differ in density and dendritic field size from the S-cone ON cells, but only in the retinal periphery.

Purpose: To investigate whether there is significant selective reduction in short-wavelength-sensitive (SWS) ganglion cell density in early to moderate glaucoma., Methods: Peripheral achromatic resolution acuity (an indirect measure of the underlying midget ganglion cell density) and peripheral chromatic resolution acuity under conditions of blue cone isolation (an indirect measure of the underlying small bistratified ganglion cell density) were measured at 13 degrees eccentricity in four oblique meridians in 15 eyes (mean age, 64.6 +/- 9.6 years) with early to moderate glaucoma. The results from the subjects with glaucoma were compared with those in a group of 17 age-matched normal eyes (mean age, 62.5 +/- 6.6 years)., Results: Mean achromatic resolution acuity across the four locations was significantly lower in the subjects with glaucoma than in the normal subjects (2.92 vs. 4.01 cyc/deg). Mean chromatic resolution acuity across the four locations was also significantly lower in the subjects with glaucoma than the normal subjects (0.78 vs. 0.99 cyc/deg). There was no selective loss of mean SWS acuity in the subjects with glaucoma. Individual location analysis revealed that the chromatic-achromatic resolution ratio was not significantly different in the subjects with glaucoma who had early glaucomatous damage when compared with the normal subjects. The chromatic-achromatic resolution ratio was lower than normal at certain locations in certain individuals with early glaucoma., Conclusions: The results indicate that there is no evidence of significant selective reduction in global SWS ganglion cell density in early to moderate glaucoma. However, there may be selective loss of SWS ganglion cell density at individual locations in individual eyes.

Spatial summation in the human visual system was studied as a function of retinal eccentricity upon selective stimulation of the short-wavelength sensitive cones. The area of complete spatial summation (Ricco's area) was found to increase with retinal eccentricity while the threshold of stimuli equal in size with Ricco's area remained constant. Comparisons with known morphology of the small bistratified retinal ganglion cells, the only cells known to be excited by S-one ON stimulation, showed that Ricco's area included 2-4 such cells and is up to 1.5 times larger than the dendritic field of a single cell. These relationships were relatively constant within the eccentricity range tested (5-20 deg along the temporal horizontal meridian) and might be the source of threshold invariance of stimuli matching Ricco's area.

A previously undescribed thraustochytrid protist, designated C9G, was isolated from the gills of a clam, Mercenaria mercenaria, collected from the Bay of Fundy, Canada. Sequence data analysis showed C9G to be related to the clam pathogen QPX, quahog parasite unknown; however, it is not enveloped by secreted mucoid material as is the case for QPX. Clam hemocytes recognized and phagocytized C9G in vitro in the absence of plasma recognition factors. Hemocytes were also capable of killing ingested C9G, as shown by the use of a tetrazolium reduction viability assay. The mechanisms underlying intracellular antimicrobial activity are not yet established, but no detectable cytotoxic reactive oxygen species were generated during phagocytosis of C9G. Clam plasma proteins were shown to inhibit C9G growth at concentrations similar to those in unfractionated hemolymph.

Previous studies have indicated that peripheral achromatic grating resolution is limited by the sampling density of the neural array (sampling limited), and largely unaffected by large amounts of optical defocus and significant changes in luminance. Under certain conditions, peripheral short-wavelength sensitive (SWS) grating acuity is also sampling limited. We wished to determine how the sampling-limited nature of SWS-driven grating resolution was affected by changing optical defocus and stimulus luminance. Using SWS-cone isolation techniques, detection and resolution acuity were measured for sinusoidal gratings under varying levels of stimulus mean luminance and optical defocus in the fovea and at 20 degrees eccentricity. From 1.4 down to 0.3 cd/m(2) peripheral detection acuity was superior to resolution acuity, accompanied by observations of aliasing: there was little change in resolution performance throughout this range. For defocus up to 3-4 dioptres, peripheral detection acuity was superior to resolution but fell steadily: resolution performance remained flat throughout the same range. Unlike achromatic acuity, foveal resolution performance displayed some robustness to defocus but to a lesser degree than the periphery. Peripheral SWS-driven resolution remains sampling limited for large changes in stimulus luminance and optical defocus, and should thus be useful as a clinical test of SWS-driven ganglion cell density., (Copyright 2002 Elsevier Science Ltd.)

Previous studies have indicated that peripheral resolution for achromatic gratings is sampling limited and directly related to the density of the underlying midget ganglion cell population. Previous studies by the authors have shown that peripheral resolution for blue-cone isolating gratings is also sampling limited, is robust to optical defocus and short-wavelength attenuation, and yields estimates of sampling density which correspond closely with the density of small bistratified ganglion cells. We measured peripheral resolution in a group of normal subjects ranging in age from 12 to 72 years, using both achromatic and blue-cone isolating gratings, to determine how performance (and hence ganglion cell density) changed with age for both systems. Resolution was higher for achromatic than blue-yellow gratings and performance was flat for both until the fifth decade. After this, performance declined for both at a rate of approximately 14%/decade with no significant difference between the two rates of decline. Individual measurements of lens density were not correlated with short-wavelength sensitive resolution performance in the older subjects, further indicating that the decline in resolution was not attributable to pre-retinal absorption., (Copyright 2002 Elsevier Science Ltd.)

Previous studies using polychromatic gratings have shown that the peripheral grating contrast sensitivity function is significantly different when the task is resolution rather than detection. Specifically, in the middle frequency range, while resolution acuity drops suddenly to zero, detection performance continues up to much higher frequencies, accompanied by observations of aliasing. We wanted to determine if the same holds true for blue-cone isolating gratings in either foveal or peripheral vision. Contrast sensitivity function (CSFs) were measured at the fovea and 20 degrees eccentricity in the temporal retina under conditions of short-wavelength-sensitive (SWS)-cone pathway isolation using a two-alternative forced choice paradigm. The detection and resolution CSF were identical at the low frequency end but at higher frequencies resolution sensitivity falls abruptly while contrast detection remained possible till higher frequencies [cut-off frequencies: fovea detection 6.0 cycles (degree)(-1), resolution 4.6 cycles (degree)(-1); periphery detection 1.6 cycles (degree)(-1), resolution 1.05 cycles (degree)(-1)]. Aliasing was observable when spatial frequency exceeded the resolution limit. Medium/high contrast blue-cone-mediated resolution acuity is sampling limited in both the fovea and periphery. Previous studies of blue-cone contrast sensitivity which employed a detection task do not reflect the true resolution limit.

Peripheral resolution acuity for achromatic gratings is known to be limited by the density of the underlying ganglion cell sampling array. After confirming isolation of the short-wavelength sensitive (SWS) system using chromatic adaptation methods, we wished to determine if resolution is limited by blue/yellow ganglion cell sampling (evidenced by a superiority of detection over resolution acuity and the perception of aliasing) and thus directly related to SWS-driven ganglion cell density. We measured detection and resolution acuity between 0 degrees and 35 degrees, using blue sinusoidal gratings superimposed on a yellow adapting background which ranged in intensity from 2.5 to 4.7logTrolands. At all locations, a break could be observed in the acuity vs. illumination curves followed by a plateau. Detection and resolution acuity were the same for low background intensities, but resolution acuity was lower than detection at higher intensities, accompanied by observations of chromatic aliasing. SWS resolution is sampling-limited across the retina and agrees well with predicted performance based on anatomical estimates of small bistratified ganglion cell density.

A device is described for use in confirming the energy constancy of clinical electron beams. A wedge shaped absorber is placed over an ionization chamber leading to an energy dependent response. A measurement under the energy filter is divided by a measurement in air to correct for the inherent energy dependence of the chamber. A nearly linear response is demonstrated.

The possibility that organophosphate toxicity is due to inhibition of targets other than acetylcholinesterase (AChE, EC 3.1.1.7) was examined in AChE knockout mice. Mice (34-55 days old) were grouped for this study, after it was determined that AChE, butyrylcholinesterase (BChE), and carboxylesterase activities had reached stable values by this age. Mice with 0, 50, or 100% AChE activity were treated subcutaneously with the nerve agent VX. The LD50 for VX was 10 to 12 microg/kg in AChE-/-, 17 microg/kg in AChE+/-, and 24 microg/kg in AChE+/+ mice. The same cholinergic signs of toxicity were present in AChE-/- mice as in wild-type mice, even though AChE-/- mice have no AChE whose inhibition could lead to cholinergic signs. Wild-type mice, but not AChE-/- mice, were protected by pretreatment with atropine. Tissues were extracted from VX-treated and untreated animals and tested for AChE, BChE, and acylpeptide hydrolase activity. VX treatment inhibited 50% of the AChE activity in brain and muscle of AChE+/+ and +/- mice, 50% of the BChE activity in all three AChE genotypes, but did not significantly inhibit acylpeptide hydrolase activity. It was concluded that the toxicity of VX must be attributed to inhibition of nonacetylcholinesterase targets in the AChE-/- mouse. Organophosphorus ester toxicity in wild-type mice is probably due to inhibition or binding to several proteins, only one of which is AChE.

Peripheral monocular grating resolution has been shown to be limited by the sampling density of the underlying retinal ganglion cells. We wanted to determine if peripheral resolution is also sampling limited binocularly; and, if so, how great is any improvement in either detection or resolution when viewing binocularly? We measured detection and resolution acuity for sinusoidal gratings in foveal and peripheral vision both monocularly and binocularly. Detection and resolution acuity were very similar in foveal vision and displayed a binocular improvement of 5% over best monocular acuity. However, in peripheral vision, while detection acuity improved by 6% binocularly, resolution acuity improved by 16%, with a subsequently smaller aliasing zone. This improvement was greater than predicted by probability summation and implies that the two monocular ganglion cell sampling arrays combine at a higher level resulting in a higher binocular sampling density.

Background: Chickenpox is prevalent in the US despite the availability of an effective vaccine. Acyclovir treatment is limited by concerns about efficacy if given after the first day of rash and by concerns about induction of viral resistance., Objective: Evaluate initiation and duration of acyclovir treatment of chickenpox and its effect on viral resistance., Study Design: Randomized, placebo-controlled, double blind trial in immunocompetent patients who were stratified by age at enrollment (children, 2 to 11 years; adolescents, > or = 12 to 18 years; adults, > or = 19 years) and duration of rash (< or = 24 h vs. >24 to 48 h). Lesions were staged, counted and cultured; temperatures and symptoms were recorded daily., Intervention: Subjects presenting within 24 h of rash onset (Group A) were randomly assigned to 5 or 7 days of oral acyclovir treatment, 80 mg/kg/day up to a maximum of 3,200 mg/day in four divided doses. Subjects whose rash was >24 to 48 h old were randomized to receive 5 days of acyclovir treatment beginning on the first (Group B1) or second study day (Group B2). Matching placebos were used to ensure that subjects uniformly received 28 doses of study compound., Results: Of the 177 subjects recruited Group A patients who were treated on the first day of rash had the greatest number of significantly shortened event times with 5 days of therapy being equivalent to 7 days. There also were some shorter times to events for Group B1 patients who began therapy on the second day of rash vs. Group B2 patients who started acyclovir on the third. These included: time to maximum lesion formation (adolescents, P = 0.007; children, P = 0.03); 50% healing in adolescents (P = 0.005); and residual facial lesions in adults (P = 0.047). The probability of viral shedding was significantly reduced for Group A subjects vs. Group B1 subjects (P = 0.006). Viruses shed during therapy remained susceptible to acyclovir and retained normal thymidine kinase function., Conclusions: Immunocompetent children, adolescents and adults with chickenpox displayed a gradation in their clinical responses to acyclovir that correlated with the time from onset of rash to initiation of therapy. Five days of therapy is sufficient because a 7-day course provided no additional benefit. The susceptibility to acyclovir of viruses shed during treatment did not change; however, the effect of therapy on resistance of latent virus was not assessed.

An equation is derived for the TG43 geometry function, G(r,theta), of a linear brachytherapy source in terms of its active length. This equation is validated by comparison to published values. It is then used to calculate values of the geometry function for the Model 200 (103)Pd seed, which is a segmented linear source.

Purpose: Previous studies of optical blur in perimetry have measured the effect of foveal refractive error on peripheral perimetric detection thresholds. Since peripheral refractive error can be significantly different from that of the fovea we wished to remove the ambiguity of previous results by correcting the actual peripheral refractive error first before adding blur., Methods: We measured detection thresholds in the fovea and at 30 degrees in the horizontal temporal field in two trained observers. Peripheral refractive error was determined at each location and thresholds measured at the same locations for stimuli ranging in size from 0.2 to 6.4 degrees and refractive errors between +/-4.00 diopters., Results: Foveal thresholds increased immediately with increasing refractive error, particularly for smaller stimulus sizes. At 30 degrees, thresholds for smaller stimuli were less affected by defocus initially and then increased more sharply. Larger stimuli were relatively unaffected by defocus such that when stimulus size reached 1.6 degrees there was little or no increase in threshold for refractive error between +/-4.00 diopters., Conclusions: Peripheral refractive error, largely forgotten by perimetrists, has a significant effect on performance, particularly for smaller stimuli. Differences in foveal vs peripheral viewing can be explained by differences in ganglion cell receptive field sizes.

A 59-year-old man presented with a Gleason score of 4 + 4 = 8 prostate cancer and with multiple bilateral pelvic nodes involved at open pelvic lymph node dissection. On indium-111 capromab pendetide (ProstaScint) scan, there was increased tracer deposition in the prostate, the mesenteric nodes, the right pulmonary hilum, and the left supraclavicular fossa. The ProstaScint injection was repeated, and the gamma probe was used to localize tissue that accumulated radiotracer. Two nodes were excised, one that exhibited increased uptake and one that did not. The radioactive lymph node contained metastatic prostate cancer. No malignancy was found in the second node.

Background: Many recent efforts to reduce unnecessary medical services have targeted care of upper respiratory infections (URIs). We tested whether patients who seek care very early in their illness differ from those who seek care later and whether they might require a different approach to care., Methods: We surveyed by telephone 257 adult patients and 249 parents of child patients who called or visited one of 3 primary care clinics within 10 days (adults) or 14 days (parents) of the onset of uncomplicated URI symptoms. Those who contacted the clinic within the first 2 days of illness were compared with those who made contact later., Results: Although 28% of adults and 41% of parents contacted their clinic within the first 2 days of symptom onset, we found very few differences in the characteristics of the caller or patient between those who called early and later. The illnesses of those who called early were not more severe, and they did not have different beliefs, histories, approaches to medical care, or needs. The only clinician-relevant difference was that adult patients calling in the first 2 days had a greater desire to rule out complications (84.7% vs 64.1% calling in 3-5 days and 70.6% calling after 5 days of illness, P < or = .05)., Conclusions: Those who seek medical care very early for a URI do not appear to be different in clinically important ways. If we are going to reduce overuse of medical care and antibiotics for URIs, clinical trials of more effective and efficient strategies are needed to encourage home care and self-management.

Chlorothalonil (TCIN) is the most commonly applied fungicide in the USA, with substantial use in the Chesapeake Bay area. Little is known about the sublethal toxicity of TCIN to fish, but since it is structurally similar to the immunotoxicant pentachlorophenol, the potential for immunomodulation exists. Previous studies have indicated that in vitro exposure of macrophages to TCIN modulates immunostimulated reactive oxygen species (H(2)O(2)/hypochlorous acid) and NADPH production in striped bass (Morone saxatilus). The goals of this study were to determine if TCIN inhibits superoxide (O(2)(-)) production by macrophage NADPH oxidase, to examine the role of cellular sulfhydryl groups in TCIN-induced macrophage dysfunction, and to identify the extent to which lipid peroxidation contributes to the observed toxic effects. The results of lucigenin-augmented chemiluminescence assays indicated that TCIN suppressed both baseline and stimulated O(2)(-) production in a dose-dependent manner. Similar results were obtained using both the particulate stimulant zymosan and the lipid-soluble stimulant phorbol 12-myristate-13-acetate. Inhibition of glutathione synthesis by pre-treatment with buthionine sulfoximine (BSO) enhanced the suppression of O(2)(-) production. The protection of sulfhydryl groups by culturing macrophages with dithiothreitol (DTT) reduced TCIN-induced macrophage dysfunction. TCIN did not initiate lipid peroxidation in macrophages, as measured by the thiobarbituric acid reactive substances (TBARS) assay, nor did pre-treatment with BSO potentiate lipid peroxidation. Because the observed TCIN-induced suppression of O(2)(-) was modulated by altering cellular sulfhydryl status with BSO and DTT, it is possible that toxicity results from the inhibition of NADPH oxidase activity by TCIN binding to its functional sulfhydryl groups.

Purpose: To assess how far retinal illumination can be reduced for sine-wave gratings phase reversing at different temporal frequencies in peripheral vision, while maintaining sampling limited resolution acuity performance, as evidenced by an aliasing zone between detection and resolution., Methods: Computer generated sine wave gratings were presented with flicker rates from 0 to 40 Hz under retinal illumination levels of 3.5 to -0.5 log trolands. Resolution and detection thresholds were measured at 30 degrees in the horizontal temporal field using a spatial and temporal 2AFC paradigm respectively., Results: At high illumination levels, detection acuity is higher than resolution acuity between 0 and 40 Hz indicating that resolution is sampling limited. As illumination level decreases the aliasing zone becomes narrower, especially at high temporal frequency until it disappears completely at 0.5 log trolands., Conclusions: Peripheral resolution acuity ceases to be sampling limited below 1.5 log trolands for low temporal frequency gratings and at higher levels for high temporal frequency gratings. Sampling limited acuity was recorded for high frequency gratings under higher illumination levels which could be mediated by the M cells alone, but this is not the case for the lower levels of illumination.

The production of reactive oxygen species (ROS) by a putative NADPH oxidase-like enzyme system is thought to contribute to antimicrobial activity in oyster hemocytes. NADPH oxidase in vertebrate phagocytes generates superoxide anion from molecular oxygen and NADPH, which is then converted to additional ROS, including H2O2 and HOCl. The fungicide chlorothalonil (TCIN) is a thiol-reactive compound that binds to protein sulfhydryl groups, which can result in enzyme inactivation. NADPH oxidase, containing several sulfhydryl groups, is a potential target of TCIN. Previous studies have demonstrated that in vitro exposure of fish (Morone saxatilus) macrophages to TCIN (10-500 microg/L) suppressed immunostimulated ROS and baseline NAD[P]H concentration but did not inhibit phagocytosis; the production of NADPH in stimulated cells was decreased only at the highest concentration. In this study, we evaluated the effects of TCIN (10-500 microg/L) on oyster hemocyte functions. As with striped bass macrophages, in vitro exposure to TCIN suppressed hemocyte ROS production in a dose-dependent manner, but did not affect phagocytosis. In contrast to the striped bass data, baseline NAD[P]H concentration was relatively unaffected and immunostimulated NAD[P]H production was marginally suppressed at the higher exposure concentrations. Despite these minor differences, these results suggest that TCIN may also be inhibiting an NAD[P]H oxidase-like enzyme in oyster hemocytes.

We develop and test two functional hypotheses based on the sampling theory of visual resolution that might account for letter acuity in peripheral vision. First, a letter smaller than the acuity limit provides insufficient veridical energy for performing the task, and, second, the available veridical energy is masked by increased amounts of visible but aliased energy. These two hypotheses make opposite predictions about the effect of low-pass filtering on letter acuity, which we tested experimentally by using filtered letters from the tumbling-E alphabet. Our results reject the masking hypothesis in favor of the energy insufficiency hypothesis. Additional experiments in which high-pass-filtered letters were used permitted the isolation of a critical band of spatial frequencies, which is necessary and sufficient for achieving maximum visual acuity. This critical band varied with the particular pair of letters to be discriminated but was in the range 0.9-2.2 cycles per letter.

Earlier studies have reported that grating resolution is sampling-limited in peripheral vision but that letter acuity is generally poorer than grating acuity. These results suggest that peripheral resolution of objects with rich Fourier spectra may be limited by some factor other than neural sampling. To examine this suggestion we formulated and tested the hypothesis that letter acuity in the periphery is sampling-limited, just as it is for extended and truncated gratings. We tested this hypothesis with improved methodology to avoid the confounding factors of target similarity, alphabet size, individual variation, peripheral refractive error, and stimulus size. Acuity was measured for an orientation-discrimination task (horizontal versus vertical) for a three-bar resolution target and for a block-E letter in which all strokes have the same length. We confirmed previous reports in the literature that acuity for these targets is worse than for extended sinusoidal gratings. To account for these results quantitatively, we used difference-spectrum analysis to identify those frequency components of the targets that might form a basis for performing the visual discrimination task. We find that discrimination performance for the three-bar targets and the block-E letters can be accounted for by a sampling-limited model, provided that the limited number of cycles that are present in the characteristic frequency of the stimulus is taken into account. Quantitative differences in acuity for discriminating other letter pairs (e.g., right versus left letters E or characters with short central strokes) could not be attributed to undersampling of either the characteristic frequency or the frequency of maximum energy in the difference spectrum. These results suggest additional tests of the sampling theory of visual resolution, which are the subject of a companion paper.

In order to better understand the interplay between metallothionein (MT) and reactive oxygen species (ROS) in oyster hemocytes, studies of the hydrogen peroxide (H2O2) scavenging properties of MT were carried out in a cell-free system. Mammalian MT is involved in protection against oxidative stress by virtue of its ability to scavenge free radicals; therefore, the H2O2 scavenging potentials of Crassostrea virginica and rabbit MTS were compared. Oyster and rabbit MTs showed similar dose-dependent suppression of H2O2-stimulated, luminol-augmented chemiluminescence (CL); the EC50 for CL (25 microM H2O2) was approximately 1.0 microM MT for both species. The interaction of ROS with MT in hemocytes could play a role in protection of the cells and surrounding tissues from oxidants associated with antimicrobial responses. Mobilization of bound zinc from MT by hemocyte-derived ROS may produce aberrant regulatory effects on various cellular processes. The data suggest that MT may be involved in immunoregulatory pathways in oyster hemocytes as a result of its ability to scavenge antimicrobial ROS.

Terminal transferase (TdT), when incubated with a purified(32)P-5"-end-labeled oligonucleotide of defined length in the presence of Co(2+), Mn(2+)or Mg(2+)and 2-mercaptoethanol in cacodylate or HEPES buffer, pH 7.2, exhibits the ability to remove a 3"-nucleotide from one oligonucleotide and add it to the 3"-end of another. When analyzed by urea-PAGE, this activity is observed as a disproportionation of the starting oligonucleotide into a ladder of shorter and longer oligonucleotides distributed around the starting material. Optimal metal ion concentration is 1-2 mM. All three metal ions support this activity with Co(2+)> Mn(2+) congruent with Mg(2+). Oligonucleotides p(dT) and p(dA) are more efficient substrates than p(dG) and p(dC) because the latter may form secondary structures. The dismutase activity is significant even in the presence of dNTP concentrations comparable to those that exist in the nucleus during the G(1)phase of the cell cycle. Using BetaScope image analysis the rate of pyrophosphorolytic dismutase activity was found to be only moderately slower than the poly-merization activity. These results may help explain the GC-richness of immunoglobulin gene segment joins (N regions) and the loss of bases that occur during gene rearrangements in pre-B and pre-T cells.

Resistance to infectious diseases in bivalves depends primarily on the vigour and efficacy of haemocyte-dependent antimicrobial defence mechanisms. Like other phagocytes, haemocytes seem to rely on oxygen-independent (lysosomal hydrolases, lysozyme) and oxygen-dependent (reactive oxygen species) mechanisms to destroy ingested microorganisms. The generation of cytotoxic oxyradicals by haemocytes can be precisely quantified by means of a simple chemiluminescence (CL) assay using luminol or other CL probes. Tributyltin (TBT), and other environmental contaminants, at sublethal levels, will produce dose-dependent suppression of CL activity in haemocytes exposed in short-term, in vitro assays. Presumably, this suppression would find expression as impaired host defence capability. In fact, TBT has been shown to exacerbate progression and lethality of Perkinsus marinus infections in the oyster, Crassostrea virginica. This suggests that CL assays on haemocytes exposed in vitro to single agents or complex mixtures might be useful in screening for aquatic immunomodulators. Statistically significant alterations in CL responses of haemocytes withdrawn from bivalves exposed to xenobiotics in the laboratory or field are more difficult to identify because of high inter-animal variation; however, the use of haemocyte CL as a biomarker of effect merits further investigation.

We measured detection and resolution acuity for vanishing optotype tumbling E stimuli in both the fovea and at 30 degrees in the periphery to determine if peripheral resolution is sampling limited for this stimulus. In the fovea, where acuity is optically limited, detection and resolution were the same. At 30 degrees, however, detection was markedly better than resolution indicating that peripheral resolution is sampling limited for this stimulus. Detection acuity was higher when contrast was 90% rather than 40%, but resolution did not change with contrast. The vanishing optotype is a legitimate perimetric stimulus to measure retinal ganglion cell density provided the task is resolution and not detection.

If reactive oxygen species (ROS) produced by hemocytes of the eastern oyster, Crassostrea virginica, impart bactericidal activity, exposure of hemocytes to bacteria should result in increased ROS generation. In an earlier study, this hypothesis was tested using luminol- and lucigenin-augmented chemiluminescence (CL) to measure ROS production. The bacterium Listonella anguillarum did not stimulate a net increase in hemocyte-derived CL, and it was suggested that bacterial antioxidants might suppress hemocyte CL. In the present study a comparison was made, under identical assay conditions, of the zymosan- and bacteria-enhanced luminol CL produced by eastern oyster hemocytes and by striped bass (Morone saxatilis) macrophages, for which L. anguillarum has been shown to be a stimulus in CL reactions. The response to zymosan produced by bass phagocytes was two orders of magnitude greater than that generated by eastern oyster hemocytes. Whereas an increase in net ROS production was not evident when oyster hemocytes were exposed to L. anguillarum, significant stimulation of striped bass macrophage-derived CL occurred. These data suggest that striped bass macrophages have a greater capacity to generate ROS than oyster hemocytes, enabling them to surpass the antioxidant capability of L. anguillarum and produce a luminol CL response.

Purpose: Currently, little or no psychophysical data exist on the decline in retinal ganglion cell density, with age or on the nature of any selective age-related loss of one cell type over another. The authors wished to determine the nature of any decline in ganglion cell density with age using measurements of peripheral grating resolution, which is directly related to ganglion cell sampling density., Methods: We measured grating resolution at 4 different retinal locations in a group of 97 normal subjects ranging in age from eight to eighty-one years. Stimuli were either stationary or employed counterphase flicker at 30 Hz in order to selectively stimulate a greater proportion of either P or M ganglion cells., Results: Mean resolution was significantly higher for stationary gratings than flickering gratings. Loss of peripheral resolution was approximately 5%/decade for stationary gratings and 6%/decade for flickering gratings. The ratio of resolution for flickering/non-flickering stimuli showed a small but insignificant decline with age., Conclusions: There is a general decline in peripheral resolution with age, indicating a corresponding loss of retinal ganglion-cell density. This age-related loss does not appear to be very selective in terms of cells that are sensitive to either stationary or flickering gratings. These results increase the diagnostic power of clinical tests that employ measures of peripheral resolution in subjects of different ages to detect diseases which cause loss of ganglion cells.

(1) Hemocytes of the oyster Crassostrea virginica were exposed to Cd in vitro to examine the concomitant induction of metallothionein (MT) mRNA and production of reactive oxygen species (ROS) during the oxidative burst response of phagocytic cells. (2) MT mRNA induction was concentration-dependent, exhibiting a threshold between 5 and 10 microM cdCl2, and an increase at higher Cd concentrations up to a maximum level of 36 microM cdCl2. Continued increases in the Cd exposure concentrations resulted in declines in the levels of MT mRna. (3) No significant effects of Cd on ROS production were observed at Cd concentrations up to 36 microM CdCl2. However, ROS production decreased in a concentration-dependent fashion at CdCl2 concentrations from 36 to 356 microM, the highest concentration tested. (4) At these higher concentrations of Cd, the concomitant decrease in MT mRNA inducibility and suppression of ROS production were probably manifestations of the general cytotoxicity of Cd. ROS suppression can result in reduced resistance to infectious agents, suggesting that Cd is immunotoxic to C. virginica.

Luminol- and lucigenin-augmented chemiluminescence (CL) were used to evaluate the ability of Listonella (formerly Vibrio) anguillarum to stimulate the production of reactive oxygen species (ROS) by Crassostrea virginica hemocytes. Whereas heat-killed L. anguillarum stimulated hemocyte CL in the lucigenin system, viable L. anguillarum did not. Neither viable nor heat-killed bacteria stimulated hemocyte production of luminol CL. Metabolically active L. anguillarum generated ROS, as indicated by luminol and lucigenin CL. It is proposed that bacterial catalase suppressed hemocyte-derived luminol CL. L. anguillarum, which possesses the antioxidant enzyme catalase, suppressed luminol CL generated by zymosan-stimulated hemocytes. Conversely, the catalase negative bacterium Carnobacterium piscicola had no effect on hemocyte-derived luminol CL elicited by zymosan. The inability of viable L. anguillarum to stimulate hemocyte ROS production, as measured by CL, does not support the proposed role for ROS in hemocyte-mediated bactericidal activity.

Knowledge about neurotransmitters, their receptors and their physiological effects has exploded in the past 15-20 years. Serotonin exerts diverse effects as a neurotransmitter and in nonneural tissues. The molecular sites of serotonin binding, re-uptake and autoregulation have proven to be viable targets for pharmacological intervention in a variety of disorders.

We measured resolution acuity at 12 different retinal locations using sinusoidal gratings in a group of normals, ocular hypertensives and glaucoma patients. Resolution was measured using both stationary gratings, which selectively stimulate parvocellular ganglion cells (P cells), and gratings which phase reversed at 30 Hz, which selectively stimulate a higher proportion of magnocellular ganglion cells (M cells). With stationary gratings, peripheral resolution was found to be significantly reduced in glaucoma patients and, to a lesser extent, in ocular hypertensives. When the stimuli phase reversed at 30 Hz these differences between groups were larger. The ratio of resolution with and without phase reversal also showed a significant difference between the three groups. These results provide strong psychophysical evidence for a selective loss of M ganglion cell density over P ganglion cell density in glaucoma.

Bedrock landsliding is a dominant geomorphic process in a number of high-relief landscapes, yet is neglected in landscape evolution models. A physical model of sliding in beans is presented, in which incremental lowering of one wall simulates baselevel fall and generates slides. Frequent small slides produce irregular hillslopes, on which steep toes and head scarps persist until being cleared by infrequent large slides. These steep segments are observed on hillslopes in high-relief landscapes and have been interpreted as evidence for increases in tectonic or climatic process rates. In certain cases, they may instead reflect normal hillslope evolution by landsliding.

Mollusks depend chiefly on hemocyte-mediated cytotoxic mechanisms such as reactive oxygen species (ROS) to defend against pathogenic microorganisms. The effect of in vitro tributyltin chloride (TBT) exposure on ROS generation by oyster (Crassostrea virginica) blood phagocytes is quantified in this study. Luminol-augmented chemiluminescence (LCL) was used to measure ROS activity of resting and zymosan-stimulated cells after 1 or 20 hr TBT exposure. LCL is thought to measure primarily the activity of the myeloperoxidase/hydrogen peroxide/ halide antimicrobial pathway. Hemocytes in TBT-free medium (controls) produced low level LCL, which was markedly stimulated by the addition of zymosan particles. Both resting and zymosan-stimulated LCL values were significantly inhibited by > or = 80 ppb TBT after either 1 or 20 hr of exposure. Exposure to < or = 2 ppb TBT concentrations for 20 hr produced slightly enhanced LCL activity, suggesting a hormesis-like effect. Partial reversibility of TBT suppression of LCL took place when previously exposed cells were put in TBT-free medium. The TBT concentrations used in these studies were not cytolethal in vitro and were considerably less than oyster tissue levels recorded after chronic, sublethal in vitro exposures. The data suggest that the common aquatic contaminant TBT can interact rapidly with C. virginica hemocytes to produce a partially reversible immunotoxicological lesion. Xenobiotic-induced suppression of ROS production by hemocytes may increase host susceptibility to infectious diseases.

This study measured spatial detection and resolution acuity thresholds at 30 deg eccentricity for sinusoidal gratings of different contrast (10-90%) that phrase reverse at different temporal frequencies (0-40 Hz). Resolution performance at any contrast displayed little deterioration with increasing temporal frequency up to 10 Hz, after which it declined smoothly, indicating no definable break where performance switched from being P-cell to M-cell mediated. Detection was measurably higher than resolution acuity for all temporal frequencies at 90%. At 50% contrast, detection and resolution performance converged at approximately 30 Hz. For 10% contrast, detection and resolution performance were the same at all temporal frequencies. These results indicate that resolution performance remains largely P-cell mediated and sampling limited over a large range of contrasts and temporal frequencies.

Detection and resolution of square patches of sinusoidal gratings were measured in central and peripheral vision (30 degrees horizontal temporal visual field) for high-contrast gratings as a function of the number of cycles in the stimulus. We determined performance in a forced-choice paradigm for a fixed number of stimulus cycles by arranging for stimulus diameter to vary inversely with spatial frequency. For both psychophysical tasks and for both target locations, the psychometric function relating performance to log spatial frequency shifted to higher frequencies without changing slope significantly as the number of cycles in the stimulus was increased. Thus the entire effect could be captured by an analysis of spatial acuity, which increased with increasing number of grating cycles over the range 0.5-6 cycles but remained constant over the range 6-14 cycles. In the central field, resolution acuity and detection acuity were equal regardless of the number of cycles in the stimulus. In the peripheral field, detection acuity exceeded resolution acuity and perceptual aliasing occurred for stimuli in the range 1-14 cycles. From this result we conclude that resolution acuity is sampling limited in the periphery, provided that the stimulus contains at least one full cycle of the grating. Essential features of the results could be accounted for by Fourier analysis of the stimulus.

Detection and resolution acuity was measured at 30 degrees in the periphery for sinusoidal gratings under differing amounts of optical defocus. Within the range -2.0 to +2.5 diopters defocus, detection acuity was higher than resolution acuity. As defocus increased, detection acuity decreased continuously but resolution acuity was little affected until around 2.0 diopters defocus. The results indicate that resolution performance is sampling limited in peripheral vision, even for significant refractive error, and is more robust than detection acuity to the effects of optical defocus.

We measured resolution at 10 degrees in the inferior temporal retina using horizontal and vertical gratings of different contrasts which modulated in time at temporal frequencies from 0 to 40 Hz. Since peripheral grating resolution is directly related to the sampling density of retinal ganglion cells this allowed us to observe changes in responding ganglion cell density as the stimulus properties changed to selectively stimulate magnocellular pathway cells (M cells) instead of parvocellular pathway cells (P cells). At all contrasts there was no decline in resolution performance up to 10 Hz, after which resolution deteriorated significantly, this effect being greater at lower contrasts. The predicted psychophysical resolution limit for M cells calculated from the anatomical data of Dacey indicates that resolution for high temporal frequency (30 Hz) or low contrast (5%) stimuli is too good to be mediated by M cells alone and there is still significant P cell stimulation by these stimuli.

Stimulation of cardiopulmonary vagal C fibers with phenyl biguanide (PBG) reflexly inhibits locomotion in addition to causing depression of blood pressure (BP), heart rate (HR), and respiration in cats and rats. We investigated whether PBG caused somatomotor inhibition during exercise in the rabbit, a species in which it is known that the hemodynamic and respiratory responses to PBG are mediated by cardiac rather than by pulmonary receptors. In eight New Zealand White rabbits, BP, HR, and hindlimb electromyographic (EMG) responses to 60 and 120 micrograms/kg PBG and saline vehicle were evaluated during two separate 3-min exercise bouts at 10 m/min at 0% grade. During exercise, 60 micrograms/kg PBG decreased BP (-27 +/- 4 mmHg) and HR (-95 +/- 16 beats/min) but did not inhibit locomotion as suggested by the EMG response (+112 +/- 8% of preinfusion EMG). Hemodynamic and EMG responses to 120 micrograms/kg PBG were similar to 60 micrograms/kg PBG. Saline infusion during exercise had no effect on HR, BP, or locomotion (+114 +/- 8% of preinfusion EMG). Locomotion is not inhibited by PBG in rabbits, which suggests that PBG-induced reflex somatomotor inhibition observed in other species is primarily mediated by pulmonary rather than by cardiac receptors.

The short-term kinetics of Zn turnover were studied in Irish setters with gluten-sensitive enteropathy and control dogs following intravenous injection of 0.25 mg 96.5% enriched 70ZnCl2. The 70Zn enrichment of serum was found closely to obey two-compartment kinetics and the derived two-compartment decay equation was used to calculate the size and turnover of the two initial rapidly exchanging pools of body Zn. In normal Irish setters isotopic Zn initially equilibrates with a pool (a) of size 1.27 (SD 0.46) mumol/kg and then with a second pool (b) of size 6.83 (SD 1.72) mumol/kg. The fractional turnover of pool (b) was approximately one eighth that of pool (a). Enteropathic dogs showed no reduction in the size of either rapidly exchangeable Zn pool, reduction in serum Zn concentration or abnormality in Zn balance and hence these results do not support the possibility of an underlying Zn deficiency in this disorder.

Luminol-dependent chemiluminescence (LDCL) and nitroblue tetrazolium (NBT) reduction assays have been used to measure reactive oxygen intermediate (ROI) production by oyster (Crassostrea virginica) hemocytes, as well as ROI modulation caused by disease or exposure to environmental toxicants. However, ROI responses measured by these tests apparently vary considerably among other bivalve species. In all species tested, unstimulated hemocytes produced small quantities of ROIs. In C. virginica and Geukensia demissa phagocytosis or treatment with phorbol myristate acetate triggered significantly augmented, but kinetically dissimilar, ROI responses; however, no induction was recorded in two clam species (Mya arenaria and Mercenaria mercenaria). This was supported by both LDCL and NBT assays, measuring activity of the myeloperoxidase/hydrogen peroxide system and production of intracellular superoxide anion, respectively. The failure of the clams to respond to standard ROI-eliciting procedures is possibly indicative of interspecies differences in hemocyte-mediated antimicrobial defense mechanisms.

Chemiluminescence (CL) was used to assay effects of pentachlorophenol (PCP) on the production of reactive oxygen intermediates (ROIs) generated by leukocytes from an estuarine teleost, Fundulus heteroclitus. Two parameters were measured during the phagocytically-induced respiratory burst: peak CL (maximal value) and total CL (temporal summation of induced values). Phagocytes obtained from the pronephros were incubated in the presence of sublethal doses of analytical (A-) or technical (T-) grades of PCP. Technical PCP has been reported to be more highly immunosuppressive than A-PCP in mammals; this effect was attributed to dioxins and other contaminants produced during manufacture. In this fish, both grades of the compound produced significant dose-dependent inhibition of peak and total CL. However, there were few significant differences between the effects of the two PCP grades on the magnitude of the CL responses at identical, sublethal concentrations, although T-PCP did produce a more marked reduction in the relative level of leukocytic CL as a function of dose than did A-PCP. Because of the probable roles of ROIs in antimicrobial blood cell-mediated mechanisms, reduced CL activity was interpreted as an indication of xenobiotic-induced immunosuppression.

Perkinsus marinus is a protozoan parasite responsible for a major infectious disease of the Eastern oyster, Crassostrea virginica. Nonspecific immunity was assayed in oysters with known intensities of infection so that the physiological responses of the host elicited by the parasite could be better understood. This report describes the capacity of hemocytes to generate reactive oxygen intermediates during the progression of the disease. The hemocytes constitute the major internal defense effector system of oysters, and cytotoxic oxygen species are thought to play central roles in antimicrobial activities of hemocytes and other phagocytic cells. Production of oxyradicals by both resting and phagocytically stimulated hemocytes was quantified by luminol-augmented chemiluminescence. Hemocytes from oysters with heavy Perkinsus infections produced significantly higher levels of chemiluminescence than their counterparts withdrawn from lightly or moderately infected individuals. Furthermore, in addition to a higher chemiluminescent activity per cell, the total circulating hemocyte count was elevated in the heavily infected animals. Therefore, advanced cases of this disease seem to be characterized by hemocyte activation and recruitment, with concomitant exuberant production of hemocyte-derived reactive oxygen intermediates. The resultant oxidant load may participate in the pathogenesis of the disease.