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Biomedical subjects

R S Anderson

Publications and source records attributed to R S Anderson.

At least 37 records · Page 2Linked to original sources

Oyster metallothionein as an oxyradical scavenger: implications for hemocyte defense responses.

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.

Animals↗

Relationship between acuity for gratings and for tumbling-E letters in peripheral vision.

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.

Discrimination, Psychological↗

Sampling limits and critical bandwidth for letter discrimination in peripheral vision.

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.

Discrimination, Psychological↗

Effect of in vitro exposure to tributyltin on generation of oxygen metabolites by oyster hemocytes.

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.

Animals↗

Psychophysical evidence for a selective loss of M ganglion cells in glaucoma.

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.

Aged↗

Metallothionein mRNA induction and generation of reactive oxygen species in molluscan hemocytes exposed to cadmium in vitro.

(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.

Animals↗

Peripheral resolution using stationary and flickering gratings: the effects of age.

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.

Adolescent↗

Serotonergic receptors as targets for pharmacotherapy.

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.

Brain↗

Effect of window size on detection acuity and resolution acuity for sinusoidal gratings in central and peripheral vision.

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.

Fovea Centralis↗

Aliasing in peripheral vision for counterphase gratings.

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.

Contrast Sensitivity↗

The selective effect of optical defocus on detection and resolution acuity in peripheral vision.

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.

Humans↗

A stable isotope study of zinc kinetics in Irish setters with gluten-sensitive enteropathy.

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.

Animals↗

Phenyl biguanide does not inhibit locomotion in conscious rabbits.

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.

Animals↗

Effect of temporal frequency and contrast on peripheral grating resolution.

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.

Contrast Sensitivity↗

In vitro immunomodulation by pentachlorophenol in phagocytes from an estuarine teleost, Fundulus heteroclitus, as measured by chemiluminescence activity.

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.

Adjuvants, Immunologic↗

Brain metastases from transitional cell carcinoma of urinary bladder.

Of 293 patients with transitional cell carcinoma of the bladder seen at our institution between April 1977 and December 1987, 9 patients were found to have brain metastasis. Seven of 9 patients were found to have a solitary brain lesion, and in 4 of these, no other site of metastatic disease was identified. Five patients received palliative whole brain irradiation, 3,000 cGy in 10 fractions, due to the presence of multiple lesions of the central nervous system (CNS) or metastases to other sites. The average survival for this group was seven weeks. One patient with a solitary brain metastasis and no other documented metastatic site was hospitalized at another institution, and was managed expectantly receiving only parenteral steroid therapy and survived four weeks. Three patients with solitary lesions and no evidence of other metastatic sites were treated with a combined surgical and radiotherapeutic approach receiving 4,000-5,000 cGy to the lesion site postoperatively. The average survival of that group was twenty-nine months, with one five-year survivor and 1 patient with no evidence of disease fourteen months after treatment. It appears that survival is longer in those patients with solitary lesions, perhaps due, at least in part, to a more aggressive therapeutic approach.

Aged↗

Psychophysical localization of the human visual streak.

In a topographical study of the human retina, Curcio and Allen documented the presence of the human visual streak, which they described as a prominent nasotemporal asymmetry in ganglion cell density. This asymmetry could also be expected to be measurable in any visual function limited by ganglion cell density. By using an interferometer we sought to test the hypothesis of Thibos et al. that peripheral resolution acuity is limited by the spacing of ganglion cells and should therefore reflect the anatomical asymmetry of the visual streak, once the attenuating effects of the eye's optics have been removed. This proved to be the case and differences predicted by a ganglion cell density of 2:1 were easily measurable. This study has potential clinical implications for the detection of disease or abnormalities of the visual system that cause death or dysfunction of retinal ganglion cells.

Cell Count↗