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Biomedical subjects

M D Davis

Publications and source records attributed to M D Davis.

155 records · Page 9Linked to original sources
PubMedDate not supplied

Behavioral and neurochemical changes in the dopaminergic system after repeated cocaine administration.

In order to determine whether repeated cocaine administration produced persistent changes in dopamine (DA) receptor binding and release consistent with behavioral sensitization, rats were treated with either cocaine (25 mg/kg ip) or saline twice daily for 14 consecutive days followed by a 3-d withdrawal period. The DA transporter site was assayed using [3H]GBR 12935, whereas D1 and D2 sites were assayed using [3H]SCH 23390 and [3H]spiperone, respectively. The density (Bmax) of the DA transporter binding sites in the ST of the cocaine-treated group increased significantly (p < 0.05) over controls 3 d after the last injection, whereas the density of striatal D1 and D2 binding sites remained unchanged. The DA transporter in the nucleus accumbens (NA) was also studied with [3H]GBR 12935 and was unchanged following drug treatment. D1 and D2 binding parameters for the NA were not determined in this study. Furthermore, cocaine administration did not affect the affinities (Kd) of the radioligands used to label the transporter, D1, or D2 sites in any of the studies performed. In addition, striatal DA release was measured using in vivo microdialysis in anesthetized rats. Linear regression analysis on maximal decreases in DA release after apomorphine (0.02, 0.2, and 2.0 mg/kg sc) injection showed no difference in the functional capacity of the ST to modulate DA transmission between control and treated groups. Moreover, animals pretreated with cocaine showed a significant (p < 0.01) decrease in locomotor activity (LA) after a presynaptic, autoregulating dose of apomorphine (0.03 mg/kg sc) was given. These results suggests that the effects seen after repeated exposure to cocaine may be regulated, in part, by changes in striatal DA transporter binding site densities and not necessarily by DA-releasing mechanisms or D1 and D2 receptor modification.

Animals↗
PubMedDate not supplied

The Wisconsin Epidemiologic Study of Diabetic Retinopathy: VIII. The incidence of retinal photocoagulation.

The incidence of focal and panretinal photocoagulation and its relationship to demographic and other characteristics were examined in a population-based study of people with diabetes in southern Wisconsin. For participants whose age at diagnosis was less than 30 years, who were taking insulin, and who had not been previously treated with photocoagulation, the 4 year incidence of panretinal photocoagulation (10.8%) was significantly higher (p less than .0001) than the rate of focal and/or grid photocoagulation of the macula (4.3%). For those whose age at diagnosis was 30 years or older and who had not been previously treated with photocoagulation, the incidence rates of panretinal photocoagulation (4.4%) and focal and/or grid photocoagulation of the macula (3.1%) were not significantly different (p = .11). At follow-up examination, 33.8% of the eyes of younger onset persons and 57.7% of the eyes of older onset persons with Diabetic Retinopathy Study high risk characteristics for severe visual loss had never received panretinal photocoagulation. These relatively high frequencies of untreated eyes in need of panretinal photocoagulation remain a concern.

Adult↗
PubMedDate not supplied

An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group.

A common detection and classification system is needed for epidemiologic studies of age-related maculopathy (ARM). Such a grading scheme for ARM is described in this paper. ARM is defined as a degenerative disorder in persons > or = 50 years of age characterized on grading of color fundus transparencies by the presence of the following abnormalities in the macular area: soft drusen > or = 63 microns, hyperpigmentation and/or hypopigmentation of the retinal pigment epithelium (RPE), RPE and associated neurosensory detachment, (peri)retinal hemorrhages, geographic atrophy of the RPE, or (peri)retinal fibrous scarring in the absence of other retinal (vascular) disorders. Visual acuity is not used to define the presence of ARM. Early ARM is defined as the presence of drusen and RPE pigmentary abnormalities described above; late ARM is similar to age-related macular degeneration (AMD) and includes dry AMD (geographic atrophy of the RPE in the absence of neovascular AMD) or neovascular AMD (RPE detachment, hemorrhages, and/or scars as described above). Methods to take and grade fundus transparencies are described.

Aged↗
PubMedDate not supplied

Ligand structure influences autologous downregulation of estrogen receptor-alpha messenger RNA.

A series of A- and D-ring substituted estrogen analogues have been examined for their effect on estrogen receptor-alpha (ERalpha) mRNA downregulation. Recently it has been proposed that ERalpha autologous downregulation occurs via transcriptional repression exerted by the binding of the ERalpha-ligand complex to the 5' region of the coding region of the ERalpha gene. Placement of the phenolic hydroxyl group on the various carbons of the aromatic A-ring of estratrien-17betaol (carbons 1-3) produced ligands which diminished the steady state level of ERalpha mRNA in relation to their affinity for receptor. 4-Hydoxyestratrien-17betaol, on the other hand, was inactive in the downregulation of ERalpha mRNA. Although this A-ring isomer brought about apparent processing of the nuclear receptor, the ERalpha reappeared in the cytosol within 24 h. Unlike the stimulation of genes regulated via estrogen response elements, maximum autologous negative regulation of the ERalpha gene required the presence of an hydroxyl group on carbon 17 of the D-ring. These results suggest that the conformational alterations elicited in the ERalpha molecule by various ligands create surfaces capable of interacting with other transcription factors in a manner which is different when the receptor functions via a response element mechanism relative to interactions during autologous negative regulation of the ERalpha gene.

Down-Regulation↗
PubMedDate not supplied

Retinopathy in young-onset diabetic patients.

The relative importance of duration of diabetes before and after 13 yr of age as a risk factor for retinopathy was investigated using data from 200 persons who were younger than 26 yr of age. These persons were identified in a population-based study of diabetic retinopathy in southern Wisconsin in 1980-1982. Retinopathy was found in 9% of persons who were younger than 13 yr and in 34% of persons who were 13 yr or older and had been diagnosed at or after 13 yr. Presence of retinopathy was more strongly associated with the duration of diabetes after 13 yr of age than before it.

Adolescent↗