Solid-phase radioimmunoassay and chemiluminoimmunoassay for somatostatin in unextracted rat plasma.

Measurement of somatostatin (SS) in small microliter volumes of rat plasma obtained from the hypophysial portal circulation would be aided by a sensitive and robust technique not dependent on extraction. We have developed radioimmunoassay (RIA) and chemiluminoimmunoassay (CIA) for SS in unextracted rat plasma from a previously described solid-phase method in human plasma. Plasma SS was captured by primary antibody bound to second antibody coated polystyrene bead. After incubation the bead was washed and [125I]Tyr1-SS added. Following overnight incubation and washing, the bead was counted. The sensitivity for 50 microliters plasma was 11 pg/ml. Parallel displacement with abdominal portal and hypophysial portal plasma was demonstrated. For direct CIA, SS was labeled with acridinium and purified using 2 sequential gradient elutions on reversed-phase HPLC. Labeled SS performed satisfactorily in solution CIA, but did not bind well in solid-phase CIA. Hence, an indirect CIA using biotinylated SS and quantitation by acridinium labeled streptavidin was established with equivalent performance to solid-phase RIA. In summary, we have developed and validated sensitive and robust solid-phase RIA and indirect CIA for SS in unextracted rat plasma. This solid-phase method could serve as a universal system for the measurement of other neuropeptides in rat plasma.

Childhood problem behavior and neuropsychological functioning in persons at risk for alcoholism.

The relationship of childhood hyperkinetic and minimal brain dysfunction (Hk-MBD) to neuropsychological functioning was examined in three groups of young adults. Nonalcoholic offspring of an alcoholic parent (N = 21) and of nonalcoholic parents (N = 21) were examined. A comparison group of similar age alcoholic patients (N = 21) was also studied. Each subject completed a battery of neuropsychological test measures and was administered a checklist on the presence of Hk-MBD symptoms in childhood. Offspring of an alcoholic parent and offspring of nonalcoholic parents could not be distinguished on the basis of their cognitive abilities or their frequency of reported Hk-MBD symptoms in childhood. Alcoholic subjects performed more poorly on measures of verbal and performance intelligence and reported a higher frequency of childhood Hk-MBD symptoms. Further, it was found that the frequency of childhood Hk-MBD symptoms was related to poor performance on certain types of cognitive tasks, regardless of group membership. These findings do not support the suggestion that certain cognitive deficits distinguish persons with a family history for alcoholism. However, poor neuropsychological performance in adulthood, at least on certain types of tasks, appears to be associated with the presence of childhood Hk-MBD.

Effect of major depression and antisocial personality on alcoholism: course and motivational patterns.

Major depression and antisocial personality are two diagnoses often associated with alcoholism. The relationship of these two diagnoses to the course of alcoholism and on the motivation for alcohol use was examined in a sample of 321 persons receiving inpatient treatment for alcoholism. Major depression did not alter the course of alcoholism in either men or women. However, patients with a history of major depression more frequently reported drinking to relieve symptoms related to depression than patients without a history of major depression. Patients with antisocial personality had an earlier onset of alcohol-related problems than patients without antisocial personality. The motivational patterns for drinking did not distinguish patients with antisocial personality from patients without antisocial personality. These findings indicate the etiological logical importance of antisocial personality for the development of alcoholism and highlight the patients' perception of depression as an explanation for their drinking.

Statistical analysis of structure-activity relationships.

The relationship between organic structure and biological activity (toxicity) is examined by statistically comparing concentration-response regression lines among structurally related compounds. Response data from acute toxicity tests are initially transformed to the logistic function while concentration data are transformed to the logarithm base 10 before being fit to a linear model using a weighted least squares analysis. A sequential approach is presented that uses statistical models for testing differences among related compounds. The approach first tests for the overall equality of regression lines (slopes and intercepts). If the regression lines are found to be different, another set of tests are conducted to determine if the slopes of the lines are equal (i.e. parallel). If the slopes are equal, multiple comparisons are made using Scheffé's procedure for determining which compounds differ in their intercepts. Relative toxicities are then estimated for various concentrations of particular compounds.