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Biomedical subjects

W Davis

Publications and source records attributed to W Davis.

At least 73 records · Page 4Linked to original sources

Bufo alvarius: a potent hallucinogen of animal origin.

Anthropologists have long speculated that ancient peoples of Mesoameria used a toad, Bufo marinus, as a ritual intoxicant. This hypothesis rests on many iconographic and mythological representations of toads and on a number of speculative ethnographic reports. The authors reject B. marinus as a candidate for such use because of the toxicity of its venom. A more likely candidate is the Sonoran desert toad, Bufo alvarius, which secretes large amounts of the potent known hallucinogen, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). The authors demonstrate that the venom of B. alvarius, although known to be toxic when consumed orally, may be safely smoked and is powerfully psychoactive by that route of administration. These experiments are the first documentation of an hallucinogenic agent from the animal kingdom, and they provide clear evidence of a psychoactive toad that could have been employed by Precolumbian peoples of the New World.

Animals↗

Inhibition of NO synthase increases the severity of kainic acid-induced seizures in rodents.

The nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine (NNA) and the putative brain-selective NO synthase inhibitor 7-nitroindazole (7-NI) were used to determine the role of endogenous NO on seizures induced by kainic acid (KA) in rats and KA, pilocarpine, bicuculline, picrotoxin and pentylenetetrazole (PTZ) in mice. Rats given a subconvulsant dose of KA (6 mg/kg, i.p.) had seizures after they had been pretreated with NNA (50 mg/kg, i.p.). With a higher dose of KA (12 mg/kg, i.p.), NNA caused an increase in wild running seizures and mortality. Unlike NNA, 7-NI had no effect on KA-induced seizures. Similarly, NNA but not 7-NI caused a worsening of seizures in mice measured as a shortening of seizure latency and an increase in wild running and mortality. The effect of NNA on seizure latency was completely reversed by the competitive substrate for NO synthase, L-arginine. NNA had no effect on seizure latency following any of the other convulsants and increased mortality following pilocarpine and picrotoxin alone. Our results indicate that NNA may enhance the severity of KA-induced seizures through suppression of NO synthase activity in the vascular endothelium. The resulting impairment of cerebrovascular autoregulation may cause a mismatch between metabolic demand and blood flow during seizures leading to facilitation of spread. The absence of a comparable effect of NNA on other seizure models may indicate differences in the degree to which seizure activity in different models is influenced by the metabolic impairment secondary to decreased blood flow.

Amino Acid Oxidoreductases↗

Cytosolic calcium elevation in response to Fc receptor cross-linking in undifferentiated and differentiated U937 cells.

We have used the calcium indicator, Fura-2, to investigate cytosolic calcium responses to cross-linking of monomeric IgG-occupied surface Fc gamma receptors (Fc gamma R), using populations of the human monocyte-like cell line, U937. The magnitude and duration of the calcium response observed, and the relative contribution to the response of internal stores and external calcium, are found to depend on the state of differentiation of these cells. Initial release of calcium from stores following Fc gamma R cross-linking is enhanced by prior treatment of U937 cells with both interferon-gamma, and, to a lesser extent, with dibutyryl cAMP. A large and prolonged entry of external calcium is observed in dibutyryl cAMP treated cells; this may be due to direct regulation of calcium channels by the low affinity receptor, Fc gamma RII (whose expression is up-regulated in these cells), since the smaller and more transient entry observed in interferon-gamma treated cells, (where the high affinity receptor, Fc gamma RI, is up-regulated) argues against a common pathway of store-mediated calcium entry.

Bucladesine↗

Winckelmann divided: mourning the death of art history.

The discipline of art history is often said to have been invented in the writing of J.J. Winckelmann (1717-1768). In his Reflections on the Imitation of Greek Works in Painting and Sculpture (1754) and History of Ancient Art (1764), Winckelmann dealt with the homoerotic meanings of Greco-Roman arts in complex ways. To do so, he imagined a split between his subjective position as an observer with specific erotic and political interests and his objective position as an historian. His importance for art historians today derives from his own recognition and further elaboration of his "division," an awareness manifested in his principal metaphor for the status of the art historian as a "maiden" mourning her "lover," the "lost object" of her desire, namely, ancient representations of beautiful young men. This metaphor and related features of Winckelmann's texts situated the homoeroticism of art and of the art historian in mutual relations that enable the art historian to reconcile, if not to resolve, his fundamental "division." Winckelmann's image of art history presents a more adequate sense of the enterprise than the misleading polarization of "objective" history and "subjective" interpretation frequently encountered today.

Art↗

Modulation of high-affinity choline carrier activity following incubation of rat hippocampal synaptosomes with hemicholinium-3.

Membrane carriers display structural and functional asymmetry with a substrate binding site which can be oriented alternately, but not simultaneously, to the extracellular and intracellular environment. Hemicholinium-3 is an inhibitor of the high-affinity choline carrier in cholinergic nerve terminals which binds to the transporter at the outer membrane surface but is not taken up into the cell. In the present study, we investigated the decline in choline transport which occurs during the first few minutes cholinergic nerve terminals are incubated in physiological salt solutions. Following incubation of rat hippocampal synaptosomes with hemicholinium-3, samples were washed free of the inhibitor and high-affinity choline uptake was measured. Choline uptake into hemicholinium-treated nerve terminals was significantly greater than control (132 +/- 4%). This effect appeared not to be due to an increase in uptake of choline above initial values in the hemicholinium-treated synaptosomes, but to a decrease in choline carrier activity in control samples by more than 25% during the first few minutes of incubation. Addition of hemicholinium-3 to samples after the preincubation induced decrease in choline uptake, followed by a wash period to remove the inhibitor resulted in elevation of choline uptake levels to initial levels. The effect of hemicholinium-3 was concentration-dependent, requiring near saturating concentrations of the inhibitor to elicit the effect. Measurement of acetylcholine content of synaptosomes at different points during the incubation procedure revealed that there was a trend for transmitter levels to vary inversely compared to choline uptake activity, but the differences were not statistically significant during treatments when significant changes in transport activity were measured.

Acetylcholine↗

Adolescent (in)vulnerability.

Three groups of subjects were asked to judge the probability that they and several target others (a friend, an acquaintance, a parent, a child) would experience various risks. Subjects were middle-class adults, their teenage children, and high-risk adolescents from treatment homes. All three groups saw themselves as facing somewhat less risk than the target others. However, this perception of relative invulnerability was no more pronounced for adolescents than for adults. Indeed, the parents were viewed as less vulnerable than their teenage children by both the adults and those teens. These results are consistent with others showing small differences in the cognitive decision-making processes of adolescents and adults. Underestimating teens' competence can mean misdiagnosing the sources of their risk behaviors, denying them deserved freedoms, and failing to provide needed assistance.

Adolescent↗

Calcitonin gene-related peptide in inflammatory bowel disease and experimentally induced colitis.

Pronounced changes in gut neuropeptide content have been observed in colonic tissues from animals with acute experimental colitis and in some patients with inflammatory bowel disease. The early decrease of CGRP in the colon during colitis in the animal studies suggest that CGRP is released during the inflammatory process. No data are available showing the biological action of released CGRP during inflammation. The sensory neurotoxin capsaicin was used in animal studies to examine the effect of sensory nerves on inflammation and healing in experimental animal models. The severity of colitis was enhanced after capsaicin pretreatment in acute and chronic animal models of colitis. These data support the hypothesis that sensory nerves exert a protective and healing-promoting function in the gut. CGRP is a good candidate for this action of sensory nerves because it is a major component in sensory nerve fibers. How CGRP exerts its protective function in the intestine is unknown. Data from gastric ulcer models support the hypothesis that a main action of CGRP is regulation of mesenteric and mucosal blood flow resulting in enhanced protection and tissue healing. Other effector roles of CGRP afferent nerve endings could also be considered.

Animals↗

Bird antigen persistence in the home environment after removal of the bird.

Hypersensitivity pneumonitis (HP) secondary to bird exposure is treated with glucocorticosteroids and avoidance. Despite therapy, symptoms may persist for a prolonged time. Just as cat antigen, Fel d 1, may persist for greater than 20 weeks after cat removal, there may be persistent bird antigen to explain prolonged symptoms in bird HP. It was the intent of this study to determine household distribution and persistence of bird antigen after removal of the bird from the patient's home. The homes of patients with birds were followed serially after bird removal with multiple samples collected using a hand-held vacuum cleaner. Bird antigen levels were determined by an inhibition enzyme-linked immunoassay. In five homes the antigen declined gradually despite extensive environmental control measures, with high levels still detectable at 18 months in one home. This data suggests that high levels of bird antigen can be detected for prolonged periods of time after bird removal and environmental cleanup. The antigen may account for the persistence of disease in some patients with HP. In severe HP, the preferred therapy may be temporary relocation of the patient away from the room in which the bird was housed, in addition to corticosteroids, until the patient's environment is demonstrated to be relatively bird antigen-free.

Air Pollution↗

A sensitive reverse passive haemagglutination immunoassay for hepatic caeruloplasmin.

A reverse passive haemagglutination assay for the measurement of caeruloplasmin in homogenates and organelle fractions prepared from needle biopsies of human liver tissue is described. Use of serial dilutions over a narrow range of concentrations permits accurate quantitation of caeruloplasmin down to 10 ng/ml, sufficient to detect the protein in needle biopsies with as little as 5 mg wet weight of tissue. Applied to the measurement of caeruloplasmin in human sera, the assay gives values which correlate well with those obtained by the standard radial immunodiffusion technique.

Biopsy, Needle↗

Calcitonin gene-related peptide and substance P decrease in the rabbit colon during colitis. A time study.

The sensory neuropeptides, substance P and calcitonin gene-related peptide, have been implicated in inflammatory reactions in several tissues. An immune-complex model of colitis was used in rabbits to determine the colonic content (nmol/g protein) of immunoreactive substance P and calcitonin gene-related peptide at various times after induction of inflammation to assess changes in these neuropeptides during the inflammatory response. Calcitonin gene-related peptide content was decreased by 66% 4 hours after induction of inflammation and reached a maximum of 80% at 48 hours. The substance P content was decreased at 8 hours, with a maximum decrease of 64% at 48 hours. Substance P decrease was detected in the muscle layer. The amounts of substance P in the mucosal/submucosal layer extracts were too low to allow accurate measurements. Calcitonin gene-related peptide decreased both in the muscle and the mucosal-submucosal layers. Immunohistochemical analysis showed that calcitonin gene-related peptide and substance P innervation patterns were comparable in normal and inflamed colon, even though there appeared to be a decrease in density and intensity of the staining, particularly for calcitonin gene-related peptide at 48 hours. The early decrease of calcitonin gene-related peptide and substance P during the time course of colitis might be due to release from nerve terminals of the gut during the inflammatory response. The profound changes in colonic calcitonin gene-related peptide and substance P content during colitis may have important implications during inflammation and subsequent tissue repair and may also lead to disturbances in gut motility.

Animals↗