Jack M. George

Enhancement of attention in man with ACTH/MSH 4-10.

Normal men were infused for 4 hr with ACTH/MSH 4-10 or a control solution. Behavioral testing after the infusion indicated that subjects who received ACTH/MSH 4-10 were less anxious and had better visual memory than control subjects but the predominant effect of the heptapeptide was to increase visual attention. It was speculated that ACTH/MSH 4-10 may be uniquely coded for attentional functioning.

Biosynthesis of Vasopressin In Vitro and Ultrastructure of a Bronchogenic Carcinoma: PATIENT WITH THE SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC HORMONE

Tumors from patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) have been found to contain large amounts of the antidiuretic hormone vasopressin. A lung tumor from a patient with hyponatremia most likely due to SIADH was removed at surgery and found to contain 23.5 mU vasopressin/g wet weight by radioimmunoassay Slices of this tumor were incubated with phenylalanine-(3)H. Arginine vasopressin-(3)H was purified from the incubate by Sephadex G-25 column chromatography in two different systems, performic acid oxidation, and gradient elution column chromatography with diethylaminoethyl Sephadex. As oxidation of vasopressin results in drastic conformational change with breaking of the ring of the cyclic polypeptide and addition of two cysteic acid residues per molecule, the radioactive material which eluted coincident with vasopressin both before and after this procedure was considered to be arginine vasopressin-(3)H. To our knowledge this is the first demonstration of in vitro biosynthesis of vasopressin by a tumor from a patient with SIADH.Ultrastructurally, the bronchogenic carcinoma was composed of small undifferentiated and granulated cells. The granulated neoplastic cells had well developed organelles (endoplasmic reticulum, free ribosomes) concerned with protein synthesis. Secretion granules present in the tumor cells were small, surrounded by a limiting membrane, and resembled those reported in polypeptide hormone-secreting cells.

Changes in pituitary oxytocin and vasopressin during the estrous cycle and after ovarian hormones: Evidence for mediation by norepinephrine

Abstract Pituitary levels of oxytocin and vasopressin were maximal on the morning of proestrus, declined during estrus, and were lowest on metestrus in cycling female rats. Norepinephrine levels in the paraventricular nucleus were decreased on proestrus and estrus when compared with metestrus-diestrus. Norepinephrine did not vary in the supraoptic nucleus. Administration of estradiol benzoate to ovariectomized rats elevated oxytocin in the pituitary 54 hr later. This elevation was not affected by a subsequent injection of estrogen or progesterone. Estrogen priming did not affect vasopressin levels in the pituitary, but a second injection of estrogen or of progesterone 48 hr later increased vasopressin in the pituitary when measured 6 hr after the second injection. Vasopressin was decreased 30 hr after a second injection of estrogen. The ovarian hormone treatments that elevated pituitary vasopressin decreased steady state levels of norepinephrine in the paraventricular nucleus and reduced the depletion of norepinephrine after administration of the catecholamine synthesis inhibitor α-methyltyrosine, suggesting a decrease in turnover. Ovarian hormones did not affect norepinephrine in the supraoptic nucleus. The present results suggest a role for posterior pituitary hormones in reproductive processes and a role for noradrenergic mechanisms in the paraventricular nucleus in mediating the effects of ovarian steroids on pituitary vasopressin.

Neuropeptide MSH/ACTH 4-10 enhances attention in the mentally retarded.

Twenty adult mentally retarded men were randomly assigned to receive MSH/ACTH 4-10 or a vehicle control solution in a double blind procedure. After an intravenous injection the subjects were presented with an orienting sequence and a series of behavioral tests. Treatment with the peptide resulted in a significant decelerative heart rate response during the test stimulus of the orienting sequence. Improved performance of the intradimensional and extradimensional shift of a visual discrimination procedure was significant for subjects receiving MSH/ACTH 4-10. The pattern of response on the subproblem analysis of the extradimensional shift reflected greater dimensional attention in the subjects treated with the peptide. Attentive subjects given MSH/ACTH 4-10 evidenced significant improvement on a rhythm matching test, a test of spatial localization and a visual retention test. The data were interpreted as indicating that the peptide resulted in improved attention of stimulus processing. It was speculated that MSH/ACTH 4-10 may be unquely coded for perceptor/attentional functioning and may be useful as a treatment for disorders of attention.

Effects of MSH/ACTH 4–10 on memory, attention and endogenous hormone levels in women☆

Abstract Young women, tested during their menstrual phase or at midcycle, received either 30 mg MSH/ACTH 4–10 or the saline diluent subcutaneously in a doubleblind procedure. Behavioral testing indicated that the peptide significantly facilitated verbal memory and impaired reversal learning ability. Visual memory, field independence, basal heart rate and state anxiety were not influenced by the treatment. Radioimmunoassays of plasma samples collected across the testing period indicated that levels of LH, FSH, 17-β-estradiol, progesterone and cortisol were not significantly altered by the peptide. It was speculated that human sex differences in response to MSH/ACTH 4–10 exist with females exhibiting an enhancement of verbal modalities.

Specific angiotensin II receptors in organ-cultured canine supra-optic nucleus cells☆

Abstract Explants of newborn puppy supra-optic nucleus were organ-cultured for 2–3 weeks, then placed in chambers, and superfused with Krebs-Henseleit buffer. Using micro-electrodes to record intracellular activity, concentration-dependent spiking activity was elicited from supra-optic nucleus neurones by superfusion with angiotensin II. Specific angiotensin antagonists blocked this activity, but did not block spiking initiated by glutamate or nicotine superfusion. It was concluded that there were specific angiotensin II membrane receptors on supra-optic nucleus neurones.

MSH/ACTH 4–10 in men and women: Effects upon performance of an attention and memory task

Abstract During two test sessions, twelve males and twelve females were subcutaneously administered 30 mg doses of MSH/ACTH4–10 or the diluent control solution in a double-blind, randomized, completely crossed design. The results indicated that in comparison to the control session, reaction time scores for the Sternberg item recognition task were significantly decreased after MSH/ACTH 4–10 administration. The reaction time scores were reduced by a nearly equal amount at each of four memory set sizes; this pattern of results suggests that the peptide exerts its effects on attention as opposed to memory. The decreased reaction times after peptide treatment occurred without a concomitant change in error rate. In addition, the order of treatment interacted significantly with the peptide treatment so that performance was apparently facilitated whether MSH/ACTH 4–10 administration preceded testing by an hour or by several days. Self-reported anxiety levels were not significantly affected by the peptide treatment. Males and females did not significantly differ on reaction time scores, error scores, or anxiety levels in the present study.

Ultrastructure of a virilizing ovarian Sertoli‐Leydig cell

A case of virilizing ovarian Sertoli‐Leydig cell tumor in a young female was studied by light and electron microscopy. The ultrastructural findings were similar to those reported in the literature and suggest the presence of two types of cells which have a common origin. The patients aunt and grandmother had had similar tumors; the one in the aunt proved malignant. The English literature review revealed the familial occurrence of virilizing ovarian tumor in only two previous cases. Virus‐like particles were seen in our case and the significance of this observation was discussed.

Cortisol and growth hormone response to surgical stress during morphine anesthesia.

HE recent popularity of morphine anesT thesia emanates in part from numerous observations suggesting an absence of cardiovascular depression following large doses of the drug. These immediate observations relate primarily to the direct effect of the drug on the heart, vessels, and autonomic nervous system. Equally important, although subtle, are the delayed drug effects, usually mediated through humoral mechanisms. In this respect, the ability of morphine to inhibit ACTH releasel and to block the pituitary-adrenal (PA) response to certain stimuli2,3 must be considered. Therefore, we elected to observe the effects of large doses of intravenous morphine on some aspects of the hypothalamic-pituitary-adrenal (HPA) function during major surgical procedures. METHODS A total of 38 patients scheduled for elective major operations were divided into six groups, a11 of whom received nitrous oxide plus: (1) halothane (control-general surgery); (2) morphine, 1 mg./kg.; (3) halothane (controlopen-heart surgery) ; (4) morphine, 2 mg./kg.; (5) morphine, 4 mg./ kg.; (6) morphine, 4 mg./kg. plus ACTH, 25 units.

Aldosterone Secretion in Hypertension

Abstract The rate of secretion and excretion of aldosterone was measured in 44 hypertensive patients. The method used for determining aldosterone secretion rate appeared to give valid results even ...