Selective impairment of auditory attention following closed head injuries or right cerebrovascular accidents.

According to clinical experience a frequent consequence of head injury is an impairment of auditory attention. We investigated the possibility that patients with either closed head injuries (CHI), or cerebrovascular accidents (CVA) of the right hemisphere, would be impaired by comparison to healthy subjects on an objective test of auditory attention. We used an experimental paradigm that consisted of four subtests which comprised strings of auditory digits heard either diotically or dichotically, at either fast or slow presentation rates, respectively. Omission and commission errors were scored for each subtest and combined by an index of errors. The results showed that CHI patients were significantly impaired initially by the fast stimulus presentation conditions, whereas CVA patients made significantly more errors on the dichotic subtests independent of the speed of presentation. It is proposed that the observed selective attention deficits of these patients were due to differential disruptions of an interactive cortical network incorporating prefrontal, anterior cingulate, and temporoparietal structures of the right hemisphere. Statistically significant correlations between the error index scores and subjectively perceived attention deficits suggested that the auditory attention task measured clinically relevant aspects of attention.

Heterogeneity of biotransformation of fluoranthene in perifused liver cells.

Pathways of biotransformation of the carcinogenic polycyclic hydrocarbon fluoranthene in individual isolated perifused liver cells were delineated using noninvasive microfluorescence spectroscopic techniques. An example of heterogeneity of coupling between phase I and phase II enzymes detected in a population of beta-naphthoflavone-induced rat liver cells demonstrates the usefulness of the experimental model of perifused liver cells.

Inhibition of androgen metabolism in stroma and epithelium of the human benign prostatic hyperplasia by progesterone, estrone, and estradiol.

It has been shown that progesterone, estrone, and estradiol are present in significant amounts in the human benign prostatic hyperplasia (BPH). Therefore it was of interest to determine the inhibitory effect of these steroids on the 5 alpha-reductase and 3 alpha (beta)-hydroxysteroiddehydrogenase (HSDH) activities, the enzymes responsible for the conversion of testosterone to 5 alpha-dihydrotestosterone (DHT), and DHT to 3 alpha (beta)-androstanediols, respectively. The enzyme inhibition was analyzed in vitro by measuring the 5 alpha-reductase in the presence of either progesterone, estrone, or estradiol, using testosterone as substrate. The DHT was used as substrate for HSDH. The metabolites were quantified by t.l.c. The main results were as follows: (1) Concerning 5 alpha-reductase in BPH, the mean inhibitor constants (KI; microM) of progesterone, estrone, and estradiol were 0.11, 15.5, and 5.1, respectively. (2) Analyzing epithelium and stroma of BPH separately, the inhibition of 5 alpha-reductase resulted in nearly identical KI's. (3) Concerning HSDH in BPH, the mean KI's of progesterone, estrone, and estradiol were 169, 63, and 192, respectively. (4) Analyzing epithelium and stroma of BPH separately, the inhibition of HSDH led to nearly identical KI's. (5) The kinetic parameters (KM, Vmax) of the 5 alpha-reduction of progesterone and testosterone were nearly identical. These results led to the suggestion that the endogenous concentrations of progesterone, estrone, and estradiol have no significant inhibitory effect on the 5 alpha-reductase and HSDH in vivo. Furthermore, the nearly identical inhibitor constants found for both enzymes in epithelium and stroma of BPH indicate that in both compartments the 5 alpha-reductase and HSDH are qualitatively identical.

Toxicological studies of liver cells by microspectrofluorometry.

The kinetics of xenobiotic biotransformation was measured in single, isolated, perifused liver cells with microspectrofluorometry using highly sensitive photodetection systems. A program of further applications to biochemical toxicological problems is presented.