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Biomedical subjects

D A Fox

Publications and source records attributed to D A Fox.

131 records · Page 8Linked to original sources
PubMedDate not supplied

Apoptosis of human T-cells: induction by glucocorticoids or surface receptor ligation in vitro and ex vivo.

Activated T-cells are susceptible to induction of apoptosis or programmed cell death in response to ligation of several cell surface structures, including CD2, CD3, and CD95/Fas. These mechanisms may be important in the regulation of immune responses and in prevention of autoimmunity. We used flow cytometric quantitation of DNA strand breaks to detect T-cells committed to programmed cell death. Activated human peripheral blood T-lymphocytes, and freshly isolated human thymocytes underwent apoptosis when exposed to dexamethasone or to monoclonal antibodies directed at CD2 or CD3. Interleukin-2 reduced spontaneous or dexamethasone-induced apoptosis, but augmented apoptosis due to ligation of CD2. A neutralizing anti-Fas antibody reduced the amount of DNA strand breakage, not only in T-cells exposed to antibodies to CD2 or CD3, but also in dexamethasone-treated cultures. In vivo activated T-cells, from inflammatory synovial fluids, were sensitive to immediate induction of DNA strand breaks without prior in vitro activation by lectin and IL-2. Taken together, the results indicated that: 1. Human lymphocytes, like murine thymocytes, are sensitive to glucocorticoid-induced apoptosis, as well as to programmed cell death triggered through surface receptors; 2. The effects of IL-2 on T-cell apoptosis depend on the apoptotic stimulus; 3. Fas/Fas ligand interactions may be relevant for both membrane receptor and glucocorticoid-induced cell death; and 4. Induction of T-cell apoptosis may be important in therapeutic effects of glucocorticoids in human disease.

Administration, Topical↗
PubMedDate not supplied

Pharmacological and biochemical evaluation of triethyltin's anticonvulsant effects.

Acute treatment of mice with triethyltin (TET) causes dose dependent anticonvulsant effects as determined by the maximal electroshock (MES) test: grade 1 (minimal) to grade 5 (maximal) seizures. Thirty minutes following 1 or 5 mg/kg TET mice exhibit 20% grade 4 and 80% grade 5 seizures or 90% grade 2 and 10% grade 3 seizures, respectively. These studies were designed to examine the neuropharmacological and neurochemical basis of this anticonvulsant effect. For MES testing, mice were injected with either reserpine, yohimbine, propranolol, haloperidol or metergoline prior to dosing with TET. Only reserpine and yohimbine blocked the previously noted anticonvulsant effects of TET. For chemical seizure testing, bicuculline ad picrotoxin were injected 30 minutes following TET. TET significantly decreased the convulsant effects of these GABAergic blockers. These results are interpreted to mean that TET preferentially interacts with the alpha-adrenergic and GABAergic transmitter systems to produce its anticonvulsant effects. In vitro receptor binding assays revealed no direct agonist activity of TET at either of these two sites. Possible alternative mechanisms are discussed.

Analysis of Variance↗
PubMedDate not supplied

Visual acuity deficits following neonatal lead exposure: cholinergic interactions.

Clinical reports describe long-term alterations in the spatial resolution properties of the visual system following developmental lead (Pb) exposure. To determine if the spatial resolution limit, visual acuity, of the adult rat was altered following low-level, neonatal Pb exposure psychophysical studies were conducted. To examine possible mechanisms of action (and an additional stressor) the effects of scopolamine were studied in the psychophysical procedure. [3H]-QNB binding was analyzed in retina, superior colliculus, lateral geniculate nucleus and visual cortex. Neonatal hooded rats were exposed to Pb (days 0-21) via the milk of dams drinking 0.2% Pb acetate. Visual acuity was 1.8 cycles/degree in controls compared to 1.3 cycles/degree in the Pb group. Scopolamine caused dose-dependent decreases in spatial resolution with decreases at higher spatial frequencies being greater in the Pb group. Positive controls revealed the effects to be centrally mediated. A decrease in the [3H]-QNB binding was found only in the visual cortex. The results suggest that long-term effects of developmental Pb exposure may be directly on the visual cortex.

Animals↗
PubMedDate not supplied

Auditory and visual dysfunction following lead exposure.

The effects of lead exposure on cognitive function have been intensively studied during the past decade, but relatively little effort has been made to understand the impact on sensory function. Subtle impairments of visual and/or auditory processing, however, could have profound effects on learning. The objectives of this paper are to review what is known about the effects of lead exposure on visual and auditory function and to identify related research needs. In particular, the effects of lead exposure on sensory function in children, which have not been studied adequately, will be discussed. Evidence from human and animal studies reveal that lead exposure impairs auditory function. The cochlear nerve and more central structures appear to be preferentially sensitive in both developing and mature humans and experimental animals. Elevations in hearing thresholds and increased latencies of brainstem auditory evoked potential have been reported at low-moderate levels of lead exposure. Higher doses of lead increase the threshold of the auditory nerve action potential, produce segmental demyelination and axonal degeneration of the cochlear nerve, but appear to have no effect on cochlear microphonics or structure. Lead exposure affects both the retina and visual cortex of the developing and mature visual system. Low to moderate level developmental lead exposure produces selective rod deficits which can be detected with electrophysiological and behavioral techniques. At slightly higher levels of lead exposure the visual cortex is affected. A wide range of functional and neurochemical effects on retinal function occurring at blood lead levels below 20 micrograms/dl, the current level of concern, have been observed in rats. Structural, biophysical and photochemical similarities of rods in rats, monkeys and humans argue the relevance of this data for pediatric lead screening. To date, however, rod-mediated visual functions have not been examined in lead-exposed children. Undetected sensory deficits of these kinds may have profound impact on the motor and mental development of children as well as on the quality of life of affected adults. There is clearly a need for more extensive sensory testing in children and workers to screen for lead-induced health effects and in animal models to clarify the mechanisms of lead neurotoxicity.

Auditory Perceptual Disorders↗