Biomedical subjects

J V Sutherland

Publications and source records attributed to J V Sutherland.

10 recordsLinked to original sources

PubMed1990

Evaluation of the interaction between D1 and D2 receptors in a drug discrimination paradigm.

Recent research has suggested that there is a synergistic interaction between D1 and D2 dopamine (DA) receptors and that D1 stimulation by endogenous DA is necessary for the expression of some D2-mediated behavioral effects. The purpose of the present experiment was to examine further the interactions between D1 and D2 receptors using drug discrimination (DD), a behavioral paradigm that is sensitive and selective for D1 and D2 agonist and antagonist activity. Two groups of male Sprague-Dawley rats (N = 8/group) were trained to discriminate the D2 agonist quinpirole (QUIN; either 0.05 or 0.012 mg/kg, ip, 10 min pre-session) from saline (1.0 ml/kg, ip, 10 min pre-session) in a two-lever, food-reinforced DD paradigm. QUIN (0.0015-0.1 mg/kg) produced a dose-related increase in QUIN-appropriate responding in both groups of rats. The D1 agonist SKF 38393 (SKF; 6.4-12.8 mg/kg, ip) given alone did not substitute for QUIN in either of the two training dose groups. The administration of SKF 30 min before QUIN had no effect on the QUIN dose-response function in either group of rats. These results indicate that stimulation of D1 receptors failed to potentiate a behavioral effect mediated by D2 receptors. The D1 antagonist SCH 23390 (SCH; 0.0015-0.05 mg/kg, ip) partially substituted for QUIN in the group trained with the 0.05 dose of QUIN, and to a larger extent in the group trained with the 0.012 dose of QUIN. SCH did not alter the effect of the training dose of QUIN except at a dose high enough to virtually eliminate lever pressing in the group trained to discriminate the high dose of QUIN. The failure of SCH to block QUIN suggests that D1 receptor stimulation by endogenous DA is not necessary for this D2 effect to be expressed. These results may be accounted for by assuming a presynaptic site of action for QUIN in the QUIN discrimination. Further, they demonstrate that the interaction between D1 and D2 receptors cannot be simply characterized as synergistic.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

Assessment of ultrasonic computed tomography in symptomatic breast patients by discriminant analysis.

From 95 subjects imaged with both speed of sound and attenuation ultrasonic computed tomography (UCT), quantitative analyses are presented on 40 cases where unequivocal correlating clinical diagnoses are available. Using four attenuation and speed of sound parameters from different regions of interest in the breast, a linear discriminator detects cancer with approximately 90% sensitivity and specificity. Increased confidence in the predictive power of this small study is given by a modern test of predictive power (jackknifing) and by the fact that diagnostic discrimination remains as high as 85% when only two parameters are employed--attenuation and speed of sound in the lesion minus those values in the remaining central mammary tissues. Speed of sound images appear particularly useful in older, fatty breasts where pulse echo ultrasound is particularly lacking. While UCT in the form studied here is not likely to receive wide clinical acceptance in the near future, a combined UCT/pulse echo system might find wide clinical utility if it can be sufficiently convenient and inexpensive.

Adenofibroma↗

PubMed1984

The multihit model of carcinogenesis: etiologic implications for colon cancer.

A new multihit model of carcinogenesis is developed for use in evaluating age-specific cancer incidence rates in human populations. The model allows for some heterogeneity in both risk (perhaps genetic) and pathway (number of hits). Fitting the model yields estimates of (1) levels of effect of background exposure to environmental agents, (2) tumor growth times after initiation of a malignant cell, and (3) relative sizes of high-risk groups in a human population. Maximum likelihood procedures are used to fit the model to the polyposis coli data of Veale and the colon cancer incidence data from the Third National Cancer Survey. Model estimates may be verified in some cases by review of independent data in the literature and results have both theoretical and practical implications. Findings are generally consistent with the adenoma-carcinoma etiologic sequence postulated by Hill, Morson and Bussey with one exception. A large proportion of the population may be at risk of four-hit colon tumors following a non-adenoma etiologic sequence.

Adolescent↗

PubMed1980

Endometrial carcinoma: clinical-pathologic comparison of cases in postmenopausal women receiving and not receiving exogenous estrogens.

Clinical and pathologic findings were compared in 43 postmenopausal endometrial carcinoma patients who had received exogenous estrogens prior to diagnosis and 79 similar patients unexposed to estrogens. Estrogen non-users were more likely to manifest lower parity, later menopause, obesity, hypertension, and diabetes, all of which have been considered to be constitutional risk factors for the development of endometrial carcinoma. Although estrogen users and non-users had similar extent of disease as judged by clinical stage, there was a tendency to more myometrial invasion in hysterectomy specimens from non-users, as well as greater frequency of unfavorable histologic types and grades of tumor. At short-term follow-up, more recurrences occurred in non-users, and this tendency appeared to be independent of clinical stage, histologic type, histologic grade, or modality of treatment. The significance of these and other observation to the determination of the risk-benefit ratio for estrogen administration is discussed.

Age Factors↗

PubMed1975