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J A Edwards

Publications and source records attributed to J A Edwards.

At least 19 recordsLinked to original sources
PubMed2006

Safety studies on epigallocatechin gallate (EGCG) preparations. Part 3: teratogenicity and reproductive toxicity studies in rats.

Green tea and its principal active ingredient, epigallocatechin gallate (EGCG), have been demonstrated to have anticancer properties through interactions with multiple biochemical processes. Since these processes are often crucial in normal fetal development it is important to evaluate the potential effects of EGCG on the fetus. EGCG preparations of >91% purity were administered to pregnant rats during organogenesis and development in order to define the safety of Teavigo, a high-concentration EGCG extract produced by the same novel method. In an initial preliminary study using subcutaneous and gavage routes, there was no evidence of any direct embryo-fetal toxicity, although some maternal toxicity was seen. In the main teratogenicity study, feeding pregnant rats diets supplemented at 1400, 4200 or 14,000 ppm during organogenesis was non-toxic to dams or fetuses. A two-generation study in rats fed 1200, 3600 or 12,000 ppm EGCG preparation showed no adverse effects on reproduction or fertility. The highest dose reduced the growth rate of offspring, and there was a slight increase in pup loss. A growth effect among pups was also seen at 3600 ppm, but in the second generation only. The lowest dose was considered the overall no-observed adverse effect level (NOAEL). As dams consumed twice the amount of feed during the crucial lactation period, the NOAEL was equivalent to 200 mg/kg/day EGCG preparation.

Abnormalities, Drug-Induced↗
PubMed2006

Safety studies on epigallocatechin gallate (EGCG) preparations. Part 2: dermal, acute and short-term toxicity studies.

Green tea extract and its principal active ingredient, epigallocatechin gallate (EGCG), are gaining attention and increased usage due to their healthful properties. Despite the increasing demand for these products, few studies have examined their safety. The toxicity of purified green tea extracts containing high concentrations of EGCG have been evaluated in a series of studies in order to define the safety of Teavigo, a high-concentration EGCG extract produced by the same novel method. Topical EGCG preparations caused minor dermal irritation in rats and guinea pigs, but not rabbits, and was a moderate dermal sensitizing agent in the guinea pig maximization test. A rabbit eye irritation test produced a strong enough response to not warrant any further testing in this assay. An oral dose delivering 2000 mg EGCG preparation/kg was lethal to rats; whereas, a dose of 200 mg EGCG/kg induced no toxicity. The dietary administration of EGCG preparation to rats for 13 weeks was not toxic at doses up to 500 mg/kg/day. Similarly, no adverse effects were noted when 500 mg EGCG preparation/kg/day was administered to pre-fed dogs in divided doses. This dose caused morbidity when administered to fasted dogs as a single bolus dose, although this model was considered an unrealistic comparison to the human condition. From these studies a no-observed adverse effect level of 500 mg EGCG preparation/kg/day was established.

Administration, Oral↗
PubMed2005

Safety studies on epigallocatechin gallate (EGCG) preparations. Part 1: genotoxicity.

Public interest in green tea has grown recently due to the potential health benefits from its consumption. Epigallocatechin gallate (EGCG), a principal polyphenolic component of green tea, is considered key to these healthful qualities. Although numerous studies have evaluated the anti-cancer effects of green tea and EGCG, few have examined the safety of EGCG consumption. The genotoxic potential of a concentrated EGCG preparation was tested in Salmonella and L5178Y tk+/- mouse lymphoma cell assays to further define the safety of Teavigo, a high-concentration EGCG extract of Camellia sinensis leaves produced by the same novel method. No mutagenic activity was detected in the bacterial system; however, a clastogenic 'trend' from the formation of hydrogen peroxide was noted in the murine cells. The oral administration of 500, 1000, or 2000 mg EGCG/kg to mice did not induce micronuclei formation in bone marrow cells. Similarly, administering 400, 800, or 1200 mg EGCG/kg/day in their diet for 10 days did not induce bone marrow cell micronuclei and produced plasma EGCG concentrations comparable to those reported in human studies. The intravenous injection of 10, 25 and 50 mg EGCG/kg/day to rats resulted in much higher plasma concentrations and demonstrated an absence of genotoxic effects. From these studies, it is concluded that Teavigo (EGCG) is not genotoxic.

Animals↗
PubMed2001

Chronic and temporarily activated causal uncertainty beliefs and stereotype usage.

In 3 studies, we examined the hypothesis that the effects of stereotype usage on target judgments are moderated by causal uncertainty beliefs and related accuracy goal structures. In Study 1, we focused on the role of chronically accessible causal uncertainty beliefs as predictors of a target's level of guilt for an alleged academic misconduct offense. In Study 2, we examined the role of chronic causal uncertainty reduction goals and a manipulated accuracy goal; in Study 3, we investigated the role of primed causal uncertainty beliefs on guilt judgments. In all 3 studies, we found that activation of causal uncertainty beliefs and accuracy concerns was related to a reduced usage of stereotypes. Moreover, this reduction was not associated with participants' levels of perceived control, depression, state affect, need for cognition, or personal need for structure. Results are discussed in terms of their implications for the model of causal uncertainty and, more generally, in terms of the motivational processes underlying stereotype usage.

Adult↗
PubMed2000

Activation of glial cells by human coronavirus OC43 infection.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease that could be triggered by a viral infection. Coronaviruses induce an MS-like disease in rodents, are neuroinvasive in humans and can infect primary cultures of human astrocytes and microglia. Infection of the human astrocytic cell line U-373MG by the OC43 strain of human coronavirus caused an upregulation of IL-6, TNF-alpha, and MCP-1 mRNA expression. This virus also modulated the activity of matrix metalloproteinases-2 and -9 and augmented nitric oxide production in both U-373MG cells and the human microglial cell line CHME-5. Thus, a coronaviral infection of glial cells could lead to the production of inflammatory molecules that have been associated with central nervous system pathologies such as MS.

Astrocytes↗
PubMed2000

Utility of real time breath analysis and physiologically based pharmacokinetic modeling to determine the percutaneous absorption of methyl chloroform in rats and humans.

Due to the large surface area of the skin, percutaneous absorption has the potential to contribute significantly to the total bioavailability of some compounds. Breath elimination data, acquired in real-time using a novel MS/MS system, was assessed using a PBPK model with a dermal compartment to determine the percutaneous absorption of methyl chloroform (MC) in rats and humans from exposures to MC in non-occluded soil or occluded water matrices. Rats were exposed to MC using a dermal exposure cell attached to a clipper-shaved area on their back. The soil exposure cell was covered with a charcoal patch to capture volatilized MC and prevent contamination of exhaled breath. This technique allowed the determination of MC dermal absorption kinetics under realistic, non-occluded conditions. Human exposures were conducted by immersing one hand in 0.1% MC in water, or 0.75% MC in soil. The dermal PBPK model was used to estimate skin permeability (Kp) based on the fit of the exhaled breath data. Rat skin K(p)s were estimated to be 0.25 and 0.15 cm/h for MC in water and soil matrices, respectively. In comparison, human permeability coefficients for water matrix exposures were 40-fold lower at 0.006 cm/h. Due to evaporation and differences in apparent Kp, nearly twice as much MC was absorbed from the occluded water (61.3%) compared to the non-occluded soil (32.5%) system in the rat. The PBPK model was used to simulate dermal exposures to MC-contaminated water and soil in children and adults using worst-case EPA default assumptions. The simulations indicate that neither children nor adults will absorb significant amounts of MC from non-occluded exposures, independent of the length of exposure. The results from these simulations reiterate the importance of conducting dermal exposures under realistic conditions.

Administration, Topical↗
PubMed2000

Assessment of the percutaneous absorption of trichloroethylene in rats and humans using MS/MS real-time breath analysis and physiologically based pharmacokinetic modeling.

The development and validation of noninvasive techniques for estimating the dermal bioavailability of solvents in contaminated soil and water can facilitate the overall understanding of human health risk. To assess the dermal bioavailability of trichloroethylene (TCE), exhaled breath was monitored in real time using an ion trap mass spectrometer (MS/MS) to track the uptake and elimination of TCE from dermal exposures in rats and humans. A physiologically based pharmacokinetic (PBPK) model was used to estimate total bioavailability. Male F344 rats were exposed to TCE in water or soil under occluded or nonoccluded conditions by applying a patch to a clipper-shaved area of the back. Rats were placed in off-gassing chambers and chamber air TCE concentration was quantified for 3-5 h postdosing using the MS/MS. Human volunteers were exposed either by whole-hand immersion or by attaching patches containing TCE in soil or water on each forearm. Volunteers were provided breathing air via a face mask to eliminate inhalation exposure, and exhaled breath was analyzed using the MS/MS. The total TCE absorbed and the dermal permeability coefficient (K(P)) were estimated for each individual by optimization of the PBPK model to the exhaled breath data and the changing media and/or dermal patch concentrations. Rat skin was significantly more permeable than human skin. Estimates for K(P) in a water matrix were 0.31 +/- 0.01 cm/h and 0.015 +/- 0.003 cm/h in rats and humans, respectively. K(P) estimates were more than three times higher from water than soil matrices in both species. K(P) values calculated using the standard Fick's Law equation were strongly affected by exposure length and volatilization of TCE. In comparison, K(P) values estimated using noninvasive real-time breath analysis coupled with the PBPK model were consistent, regardless of volatilization, exposure concentration, or duration.

Administration, Cutaneous↗
PubMed1999

The FLF MADS box gene: a repressor of flowering in Arabidopsis regulated by vernalization and methylation.

A MADS box gene, FLF (for FLOWERING LOCUS F ), isolated from a late-flowering, T-DNA-tagged Arabidopsis mutant, is a semidominant gene encoding a repressor of flowering. The FLF gene appears to integrate the vernalization-dependent and autonomous flowering pathways because its expression is regulated by genes in both pathways. The level of FLF mRNA is downregulated by vernalization and by a decrease in genomic DNA methylation, which is consistent with our previous suggestion that vernalization acts to induce flowering through changes in gene activity that are mediated through a reduction in DNA methylation. The flf-1 mutant requires a greater than normal amount of an exogenous gibberellin (GA3) to decrease flowering time compared with the wild type or with vernalization-responsive late-flowering mutants, suggesting that the FLF gene product may block the promotion of flowering by GAs. FLF maps to a region on chromosome 5 near the FLOWERING LOCUS C gene, which is a semidominant repressor of flowering in late-flowering ecotypes of Arabidopsis.

Arabidopsis↗
PubMed1999

Light-induced calcium influx into retinal axons is regulated by presynaptic nicotinic acetylcholine receptor activity in vivo.

Visual activity is thought to be a critical factor in controlling the development of central retinal projections. Neuronal activity increases cytosolic calcium, which was hypothesized to regulate process outgrowth in neurons. We performed an in vivo imaging study in the retinotectal system of albino Xenopus laevis tadpoles with the fluorescent calcium indicator calcium green 1 dextran (CaGD) to test the role of calcium in regulating axon arbor development. We find that visual stimulus to the retina increased CaGD fluorescence intensity in retinal ganglion cell (RGC) axon arbors within the optic tectum and that branch additions to retinotectal axon arbors correlated with a local rise in calcium in the parent branch. We find three types of responses to visual stimulus, which roughly correlate with the ON, OFF, and SUSTAINED response types of RGC reported by physiological criteria. Imaging in bandscan mode indicated that patterns of calcium transients were nonuniform throughout the axons. We tested whether the increase in calcium in the retinotectal axons required synaptic activity in the retina; intraocular application of tetrodotoxin (10 microM) or nifedipine (1 and 10 microM) blocked the stimulus-induced increase in RGC axonal fluorescence. A second series of pharmacological investigations was designed to determine the mechanism of the calcium elevation in the axon terminals within the optic tectum. Injection of bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid-AM (BAPTA-AM) (20 mM) into the tectal ventricle reduced axonal calcium levels, supporting the idea that visual stimulation increases axonal calcium. Injection of BAPTA (20 mM) into the tectal ventricle to chelate extracellular calcium also attenuated the calcium response to visual stimulation, indicating that calcium enters the axon from the extracellular medium. Caffeine (10 mM) caused a large increase in axonal calcium, indicating that intracellular stores contribute to the calcium signal. Presynaptic nicotinic acetylcholine receptors (nAChRs) may play a role in axon arbor development and the formation of the topographic retinotectal projection. Injection of nicotine (10 microM) into the tectal ventricle significantly elevated RGC axonal calcium levels, whereas application of the nAChR antagonist alphaBTX (100 nM) reduced the stimulus-evoked rise in RGC calcium fluorescence. These data suggest that light stimulus to the retina increases calcium in the axon terminal arbors through a mechanism that includes influx through nAChRs and amplification by calcium-induced calcium release from intracellular calcium stores. Such a mechanism may contribute to developmental plasticity of the retinotectal system by influencing both axon arbor elaboration and the strength of synaptic transmission.

Animals↗
PubMed1997

Androgen stimulation of lacrimal gland function in mouse models of Sjögren's syndrome.

Sjögren's syndrome, an autoimmune disease that occurs primarily in women, causes extensive inflammation and significant dysfunction in the lacrimal gland, and is one of the leading causes of dry eye syndromes throughout the world. Recently, our research has shown that androgen treatment causes a significant suppression of the immunopathological lesions in lacrimal tissues of female mouse models (MRL/Mp-lpr/lpr [MRL/lpr] and NZB/NZW F1 [F1]) of Sjögren's syndrome. To extend these findings, the objective of the present study was to determine whether this androgen-induced anti-inflammatory action may be paralleled by an increase in the functional activity of lacrimal glands in these autoimmune mice. Towards this end, we measured the tear levels of immunoglobulin A (IgA), which originates from lacrimal tissue and whose concentration is known to be diminished in mucosal sites in Sjögren's syndrome. For comparative purposes, we also evaluated whether the administration of other steroid hormones or immunosuppressive agents might duplicate possible androgen effects on the secretory function of lacrimal tissue. Female MRL/lpr and F1, as well as non-autoimmune BALB/c, mice were treated with vehicle, steroids or immunosuppressive compounds for 17 to 54 days after the onset of disease. Lacrimal glands, tears and sera were collected immediately before (pretreatment), or after, therapy and processed for the analysis of either tear IgA (enzyme-linked immunosorbent assay; ELISA) and protein content or the magnitude of lymphocyte infiltration (computer-assisted image analysis). Our findings demonstrated that testosterone treatment stimulated a significant increase in the concentration and total amount of tear IgA, as well as tear protein, compared to levels in pretreatment or placebo controls. This hormone action was reproduced by exposure to a diverse array of "anabolic" and "androgenic" androgen analogues, but not by treatment with estradiol, danazol, cyclosporine A, dexamethasone or cyclophosphamide. In contrast, only dexamethasone increased serum IgA concentrations. Of particular interest is the fact that the androgen control of IgA output by the lacrimal gland appeared to be independent of this steroid's suppression of lymphocyte infiltration in lacrimal tissue. Overall, these results show that androgen therapy enhances the functional activity of the lacrimal gland in mouse models of Sjögren's syndrome.

Androgens↗
PubMed1996

Identification and endocrine control of sex steroid binding sites in the lacrimal gland.

Previous research has indicated that the lacrimal gland may be a target organ for sex steroids and that androgen effects on this tissue may be inhibited by pituitary deficiency or diabetes. To extend these findings, the objectives of the current investigation were 3-fold: [a] to determine whether specific and high-affinity binding sites for androgens and estrogens exist in rat lacrimal tissue; [b] to assess whether the number and affinity of androgen binding sites in the lacrimal gland may be influenced by hypophysectomy or acute diabetes; and [c] to examine whether androgen receptor mRNA may be detected in lacrimal tissues of a variety of species. Following the collection of lacrimal gland samples, tissues were processed for the conduct of equilibrium binding methods or molecular biological techniques. Our results demonstrated that a single class of saturable, high-affinity and stereochemically selective binding sites for androgens exist in lacrimal tissues of male and female rats. These sites possessed a dissociation constant of approximately 1 nM and were also present in isolated acinar epithelial cells. In contrast, we were unable to find any evidence for the presence of specific or high-affinity receptors for estrogens in the rat lacrimal gland. With regard to changes in the endocrine environment, hypophysectomy led to an increase in the number and affinity of androgen binding sites in rat lacrimal tissue cytosol, whereas diabetes reduced the total quantity of these sites. Of interest, androgen receptor mRNA was detected in lacrimal glands of mice, rats, hamsters, guinea pigs, rabbits and humans. Overall, our findings show that the lacrimal gland is a target organ for androgens and that androgen action in this tissue may be mediated through an interaction with specific and high-affinity binding sites.

Adult↗
PubMed1994

Individual differences in causal uncertainty.

This article presents a scale that measures chronic individual differences in people's uncertainty about their ability to understand and detect cause-and-effect relationships in the social world: the Causal Uncertainty Scale (CUS). The results of Study 1 indicated that the scale has good internal and adequate test-retest reliability. Additionally, the results of a factor analysis suggested that the scale appears to be tapping a single construct. Study 2 examined the convergent and discriminant validity of the scale, and Studies 3 and 4 examined the predictive and incremental validity of the scale. The importance of the CUS to work on depressives' social information processing and for basic research and theory on human social judgment processes is discussed.

Adult↗
PubMed1993

Perfecting research techniques in an imperfect world: response to MacWhinney & Snow.

Edwards (1992c) concerns data and data use rather than manuals. It presents principles to facilitate reliable archive research in an imperfect world. MacWhinney & Snow (1992) endorse the principles but disagree on important details, discussed in this response. M&S underrate the impact of corpus inconsistencies on substantive conclusions. Since acquisition research concerns events which often trickle in a few at a time, main findings often involve a handful of examples, so overlooking a single early variant can seriously skew results. Until archives become perfect, if they do, type-token listings can help in identifying variants before computer search and avoiding this hazard.

Child Language↗
PubMed1993

Depression and the impression-formation continuum: piecemeal processing despite the availability of category information.

A study explored depressed-nondepressed differences in impression formation. From S. T. Fiske and S. L. Neuberg's (1990) model of impression formation, mildly depressed perceivers were hypothesized to engage in more piecemeal processing when forming an impression of a target other, even when nondepressed perceivers would typically use less effortful, categorical processing. With an idiographic technique designed by M. Pavelchak (1989), depressed Ss were shown to use trait attributes in evaluating a person, even when induced to categorize the individual. Nondepressed Ss relied on category information when available, replicating Pavelchak's study. Depressed Ss' results are interpreted as arising from a motivation to engage in effortful analysis of social information, stemming from feelings of lack of control over life events.

Adult↗
PubMed1993

Electromyographic evaluation of closed and open kinetic chain knee rehabilitation exercises.

The use of closed kinetic chain knee rehabilitation exercises has been advocated in recent years. The primary reason cited for employing closed kinetic chain exercises is that these exercises result in less anteroposterior (A/P) shear force at the knee joint, when compared with traditionally used open kinetic chain exercises. The purpose of this study was to determine the electromyographical (EMG) activity ratio of quadriceps to hamstrings occurring in the following exercises: unilateral one quarter squats, leg extensions (N-K Table), lateral step-ups, and movements on the Fitter (Fitter International, Inc), Stair-master 4000 (Randal Sports/Medical Products, Inc), and slideboard. Ten female student-athletes participated in this study. EMG surface electrodes were applied over the rectus femoris and biceps femoris muscles. The subjects completed three maximum isometric contractions for both muscle groups to obtain baseline EMG data. They then performed repetitions of each exercise. These movements were videotaped simultaneously with a stationary shuttered video camera operating at 30 Hz. A computer program was used to analyze the videotaped performances for knee joint range of motion (ROM). Three trials of data were averaged. Baseline EMG activity was used to determine percentage of maximum EMG activity for each exercise. There were significant differences (p.<01) among the exercises for the following dependent variables: ROM, maximum angle, percent of maximum contraction, time of contraction, and total EMG (EMG area under the curve). This study suggests that the five closed kinetic chain exercises studied result in minimal A/P shear forces at the knee joint.

Journal Article↗
PubMed1992

Quantitative comparison of radiolabeled antibody therapy and external beam radiotherapy in the treatment of human glioma xenografts.

Using 90Yttrium radiolabeled antibodies, radioimmunotherapy was compared to fractionated external beam radiotherapy in the treatment of human glioma xenografts. Antibody treatments required administration of an approximately threefold greater total dose compared to external beam treatments to achieve the same tumor regrowth delay. Following multi-fraction external beam radiation treatments, tumor regrowth delay demonstrated a large fractionation effect (alpha/beta = 2.3 Gy, 95% confidence limits 0.4-4.2 Gy), suggesting that much of the ineffectiveness of the antibody treatments could be caused by a large dose-rate effect in this system. Despite the large fractionation effect, the regrowth delay was small for a large single-fraction external beam irradiation, possibly because of tumor hypoxia. When compared to external beam radiation, radiolabeled antibody treatments resulted in a comparatively diminished tumor bed effect, suggesting radioimmunotherapy spares normal tissue surrounding the tumor.

Animals↗