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Biomedical subjects

A G Robinson

Publications and source records attributed to A G Robinson.

At least 109 records · Page 6Linked to original sources

DDAVP in the treatment of central diabetes insipidus.

DDAVP, 1-desamino-8-d-arginine-vasopressin, is a synthetic analogue of vasopressin with increased antidiuretic activity and decreased pressor activity. Whereas the antidiuretic-to-pressor ratio of arginine vasopressin is 1, the antidiuretic-to-pressor ratio of DDAVP is 4000. When administered as an intranasal spray, 5 to 20 mug of DDAVP produced eight to 20 hours of antidiuresis in patients with complete central diabetes insipidus. The minimum recommended therapeutic dose resulted in a maximum antidiuresis in most patients. No side effects of the drug were noted in clinical trials. DDAVP thus gives promise of becoming the standard treatment of severe central diabetes insipidus.

Catheterization↗

Simultaneous ectopic production of parathyroid hormone and calcitonin.

Two patients with cancer were evaluated in whom there was evidence for the simultaneous ectopic production of parathyroid hormone (PTH) and calcitonin (CT). One patient had a gastric carcinoid and the other had a pancreatic islet cell carcinoma. Abnormal concentrations of parathyroid hormone and calcitonin were demonstrated by radioimmunoassay in the peripheral blood of each patient and in the gastric tumor. In the pancreatic tumor, immunohistologic studies also demonstrated the presence of CT and PTH and suggested that each hormone was produced by different cells of the tumor. Plasma concentrations of the hormones responded to functional tests of secretion and to tumor chemotherapy. These studies demonstrate the simultaneous ectopic production of the two physiologically antagonistic hormones, PTH and CT, and confirm their value as diagnostic markers for several types of malignancies.

Adenoma, Islet Cell↗

Plasma neurophysin levels in monkeys: emphasis on the hypothalamic response to estrogen and ovarian events.

Specific radioimmunoassays for human neurophysins released in response to estrogen (estrogen-stimulated neurophysin, ESN) and nicotine (nicotine-stimulated neurophysin, NSN) have been used to measure two similar neurophysins in rhesus monkey plasma. As in the human, concentrations of rhesus monkey neurophysins in plasma were specifically produced a marked increase of plasma NSN concentrations in the monkey. Estradiol benzoate administered intramuscularly consistently produced an increase in plasma ESN concentrations in normal cycling and castrate monkeys. ESN response to estrogen was exclusively positive and occurred approximately 10 hours after an injection of estradiol benzoate intramuscularly. Plasma samples obtained throughout the mid-cycle were measured and a characteristic rise in estrogen and LH, and a more prolonged rise in ESN were found. Our data indicate that the ESN and LH responses to estrogen stimulation are temporally related events and that the assay of ESN in plasma may be of unique value as it directly reflects the hypothalamic response to changes in estrogen secretion.

Animals↗

The hypothalamic-neurohypophysial system of the rat: localization and quantitation of neurophysin by light microscopic immunocytochemistry in normal rats and in Brattleboro rats deficient in vasopressin and a neurophysin.

The cellular distribution of neurophysin was examined in hypothalami and neural lobes of normal Long-Evans rats and Brattleboro rats deficient in vasopressin and a major neurophysin. Tissue sections were treated with antisera to bovine, human, and rat neurophysins, using immunoperoxidase bridge techniques. Antisera to oxytocin (OT) and vasopressin (VP) were applied to adjacent sections. Two distinct cell populations were discernible in both magnocellular nuclei on the basis of the intensity of cytoplasmic staining. About half of the magnocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of homozygous Brattleboro rats with diabetes insipidus (DI) were devoid of immunoreactive neurophysin, OT, and VP. These cells were presumably the defective counterparts of those neurons that produce VP and its associated neurophysin in normal and heterozygous Brattleboro rats. The cells in homozygous DI rats which were stained with immunoreaction products to NP and OT were more concentrated in the dorsal part of the SON and in the periphery of the PVN. Spatial segregation of different neurons was also seen in the neural lobe, where clusters of stained axons were surrounded by bundles of nerve fibers lacking immunoreactive material. In normal rats and heterozygotes nearly all magnocellular neurons reacted immunologically with antiserum to neurophysin but with different intensities, so that "dark" and "light" cells could be distinguished. The darker cells in heterozygous Brattleboro rats had the same pattern of distribution as cells which contained OT. In homozygous DI rats, only some of those cells which contained neurophysin and OT exhibited a positive reaction with antiserum to VP due to slight reactivity with OT. The results obtained in the homozygous Brattleboro rat would suggest that OT and VP and their associated neurophysins are produced in different neurons in both the SON and PVN. However, in normal rats and in heterozygous Brattleboro rats, VP appeared to be present in both OT-positive and OT-negative neurons suggesting that some cells may have the capacity to synthesize two hormones.

Animals↗

Isolation, assay, and secretion of individual human neurophysins.

Human neurophysin was isolated from acetone-dried human posterior pituitaries and separated into two major neurophysin peptides by ion exchange chromatography and into four major peptides by preparative disk gel electrophoresis. Antisera raised in rabbits distinguished only two specific antigenic sites on the isolated neurophysin peptides. Individual sensitive and specific radioimmunoassays for two human neurophysins were developed. These assays were used to measure each neurophysin in unextracted human plasma. The two neurophysins are secreted independently in man. One assay measures a neurphysin that is specifically secreted in response to estrogen administration, estrogen-stimulated neurophysin (ESN). The other assay measures a neurophysin that is specifically secreted in response to cigarette smoking, nicotine-stimulated neurophysin (NSN). The mean ESN is 1.1 ng/ml plus or minus 0.7 SD in women and 1.0 ng/ml plus or minus 0.7 SD in men. The mean NSN is 0.9 ng/ml plus or minus 0.2 SD in women and 0.6 ng/ml plus or minus 0.3 SD in men. It is proposed that these may prove to be a specific human "oxytocinneurophysin," ESN, and a human "vasopressin-neurophysin," NSN.

Animals↗

Nicotine-stimulated release of neurophysin and vasopressin in humans.

Nicotine stimulation, induced by cigarette smoking, has previously been identified as a potent stimulus for vasopressin release in humans. In this study, radioimmunoassay measurements of plasma vasopressin and human neurophysin were performed on samples taken from 14 normal subjects during cigarette smoking. Significant rises in vasopressin occurred in 10 of the 14 subjects and the same 10 had significant rises in neurophysin. Pretreatment with ethanol in 3 subjects either eliminated or greatly blunted the responses of both vasopressin and neurophysin to cigarette smoking. These studies indicate that the release mechanisms for vasopressin and neurophysin are closely linked in humans.

Adult↗

Elevation of plasma neurophysin in women on oral contraceptives.

The effect of oral contraceptives on the neurohypophysis was demonstrated by changes in the plasma level of a posterior pituitary protein. neurophysin. Neurophysins are intraneuronal proteins associated with oxytocin and vasopressin. They have been shown to be released into the bloodstream. The resting plasma level of neurophysin in normal nonpregnant women is 0.69 ng/ml+/-0.7 SD. In women on oral contraceptives, the plasma level is 6.4 ng/ml+/-4.2 SD (P<0.001). Estrogen rather than progesterone causes the elevated neurophysin. The effect is observed within 12-24 h of estrogen administration and disappears 3-11 days after estrogen is discontinued. The results indicate that oral contraceptives act on the neurohypophysis and that estrogen is a potent pharmacologic stimulus useful in studying synthesis and release of neurophysin.

Adult↗

Vasopressin and neurophysin: high concentrations in monkey hypophyseal portal blood.

Vasopressin and its binding protein, neurophysin, were measured by radioimmunoassay in the hypophyseal portal blood of monkeys after cannulation of individual long portal veins. Mean vasopressin concentrations (13,800 picograms per milliliter) in portal blood were more than 300 times as high as those in the systemic circulation (42 picograms per milliliter). Neurophysin concentration was approximately 25 times as high in portal as in systemic blood. By immunoperoxidase techniques, high concentrations of neurophysin were demonstrated around portal capillaries of the median eminence. These studies indicate direct secretion of vasopressin and neurophysin into the portal circulation; the quantities secreted during stress may be sufficient to exert significant effects on secretion of anterior pituitary hormone.

Animals↗

Cerebrospinal fluid and ependymal neurophysin.

Neurophysins are "carrier proteins" associated with vasopressin and oxytocin in the neurohypophyseal system. The release of these hormone associated proteins may serve as an indicator of posterior pituitary function. This report describes the measurement of neurophysin in human and monkey plasma and cerebrospinal fluid (CSF) by radioimmunoassay. Tissue neurophysin is also localized in monkey brain by the immunoperoxidase technique. CSF from 68 patients and five monkeys had easily measurable neurophysin in every sample. The concentration of neurophysin in CSF and in plasma of man is 5.4+/-0.30 ng/ml (mean and SEM) and 0.69+/-0.04, respectively. The two means were significantly different (P < 0.001). In paired plasma and CSF specimens which were obtained simultaneously from each of 13 human and five monkey donors, the concentrations of neurophysin in CSF were greater than those of plasma in every case (paired t test, P < 0.001). Neurophysin administered intravenously to dogs did not enter CSF. Using the immunoperoxidase technique, we found neurophysin not only in the supraoptic and paraventricular nuclei, their tracts, and the posterior pituitary, but also in the specialized ependymal tanycytes of the infundibular recess of the third ventricle and in the external layer of the median eminence where capillaries drain into hypophyseal portal vessels. Neurophysin may pass from CSF to portal vessels via tanycytes in a manner similar to that postulated for releasing factors.

Animals↗