Adenosine A2A receptors modulate the binding characteristics of dopamine D2 receptors in stably cotransfected fibroblast cells

In membrane preparations from rat striatum, where adenosine A2A and dopamine D2 receptors are coexpressed, stimulation of adenosine A2A receptors was found to decrease the affinity of dopamine D2 receptors for dopamine agonists. We now demonstrate the existence of this antagonistic interaction in a fibroblast cell line (Ltk-) stably transfected with the human dopamine D2 (long-form) receptor and the dog adenosine A2A receptor cDNAs (A2A-D2 cells). In A2A-D2 cells, but not in control cells only containing dopamine D2 receptors (D2 cells), the selective adenosine A2A agonist 2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethyl-carboxamido adenosine (CGS 21680) induced a 2-3-fold decrease in the affinity of dopamine D2 receptors for dopamine, as shown in competition experiments with dopamine versus the selective dopamine D2 antagonist [3H]raclopride. By contrast, activation of the constitutively expressed adenosine A2B receptors with 5'-N-ethyl-carboxamidoadenosine (NECA) did not modify dopamine D2 receptor binding. In A2A-D2 cells CGS 21680 failed to induce or induced only a small increase in adenosine-3',5'-cyclic-monophosphate (cAMP) accumulation. In D2 cells NECA- or forskolin-induced adenylyl cyclase activation was not associated with any change in dopamine D2 receptor binding. These results indicate that adenylyl cyclase activation is not involved in the adenosine A2A receptor-mediated modulation of the binding characteristics of the dopamine D2 (long-form) receptor.     

The effect of kind of carbohydrate in the diet and use of oral contraceptives on metabolism of young women. II. Serum lipid levels

The response of lipids in the blood between two groups of six young women was compared. Group 1 took oral contraceptives and group 2 had never taken oral contraceptives. Two experimental diets supplied about 13% of the calories from protein, 36% from fat, and 51% from carbohydrate. Of the carbohydrate, 84% was either sucrose or wheat starch. Each diet was fed for 4 weeks in a cross-over design. In the portion of the research presented here, subjects were fed a high sucrose meal before each dietary period and after weeks 1 and 3 of each dietary period. Blood lipids were measured before and 30, 60, 120, and 180 min after each meal. Cholesterol and lipoproteins were not affected by the sucrose meal, but free fatty acid levels decreased significantly in both groups. The serum levels of triglycerides, beta-lipoproteins, and cholesterol were significantly higher in users than in nonusers of oral contraceptives. Free fatty acid levels were affected by an interaction between diet and time, and the decrease in response was greater after the sucrose than after the wheat starch diet. Triglycerides, cholesterol, and total lipids were not significantly different after the two carbohydrate diets.     

A population-based exposure model for benzene

A model of daily-average inhalation exposures and total-absorbed doses of benzene to members of large populations was developed as part of a series of multimedia exposure and absorbed dose models. The benzene exposure and dose model is based upon probabilistic rather than sequential simulation of time-activity patterns, a simpler approach to modeling personal benzene exposures than other existing models. An important innovation of the benzene model is the incorporation of an anthropometric module for generating correlated exposure factors used to estimate absorbed doses occurring from inhalation, ingestion, and dermal absorption of benzene. A preliminary validation exercise indicates that the benzene model produces reasonable estimates of the distribution of benzene personal air concentrations expected for a large population. Uncertainty about specific percentiles of the predicted distributions of personal air concentrations was found to be dominated by uncertainty about microenvironmental benzene concentrations rather than time-activity patterns, and uncertainty about total absorbed doses was dominated by a lack of knowledge about the true absorption coefficient for benzene in the lung rather than knowledge gaps about microenvironmental concentrations or intake rates. The results of this modeling effort have implications for environmental control decisions, including evaluation of source control options, characterization of population and individual risk, and allocation of resources for future studies.     

Prolonged disease-free survival in bronchogenic carcinoma associated with HLA-Aw19 and HLA-B5. A two-year prospective study

Seventy patients with squamous carcinoma or adenocarcinoma of the lung were HLA typed at the time of their diagnosis and initial therapy. No abnormal HLA antigen frequencies were found. However, the possession of HLA-Aw19 or HLA-B5 was significantly correlated with two year disease-free survival. Twelve of 21 patients (57%) with either Aw 19 or B5 were disease-free at two years. In contrast, only six of 48 patients (13%) not having either antigen were disease-free (p less than .001). One patient was lost to follow-up. It is possible that Aw 19 and/or B5 confer resistance to progression of bronchogenic carcinoma on their possessors.     

Whisky: a new provacative test for calcitonin secretion

Oral whisky is a potent stimulus of calcitonin secretion. Peak increments of immunoreactive calcitonin are observed within 15 min after the ingestion of 50 ml of whisky; the magnitude of the response is similar to that observed during a four-hour calcium infusion. This procedure has several advantages over standard methods of stimulating calcitonin release in patients at risk of developing medullary carcinoma of the thyroid, and this is shown by a study in a large family with familial chromaffinomatosis.