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Biomedical subjects

J A Parsons

Publications and source records attributed to J A Parsons.

At least 55 records · Page 3Linked to original sources
PubMed1982

Effects of anti-oxytocin serum in Brattleboro rats.

Brattleboro rats were housed singly in metabolic cages and continuously infused with saline. Timed urine collections were analyzed for Na+ and K+; oxytocin (OT)-like material was estimated by RIA. OT infusions reduced urine flow and increased Na+ output. Urinary Na+/K+ ratios rose during OT infusion, falling below control values after infusion. Passive immunization with an OT antiserum reduced but did not prevent these renal effects of OT. In a second experiment, immunization had no effect on daily urine volume or Na+ output, even though high titers were achieved and excretion of endogenous OT-like material was reduced. We conclude that endogenous OT has little effect on Na+ excretion in these rats, although pharmacological doses of OT produced their known natriuretic effect.

Animals↗
PubMed1982

Parathyroid hormone stimulates the bone apposition rate independently of its resorptive action: differential effects of intermittent and continuous administration.

The deposition of mineralized bone matrix by differentiated osteoblasts was studied in rats in vivo by labeling the bone with three doses of tetracycline given at 48-h intervals. Only bone formation loci bearing all three tetracycline doses were measured, thus eliminating sites where bone formation was not continuous during the labeling period. Using this technique, the effects of intact bovine parathyroid hormone [bPTH-(1-84)] and of a synthetic amino-terminal fragment of human PTH [hPTH-(1-34)] were measured in thyroparathyroidectomized animals. bPTH-(1-84), administered sc, and hPTH-(1-34), administered iv, caused a dose-dependent increase in the bone apposition. Subcutaneous administration of hPTH-(1-34) in doses varying from 2.7-173.0 pmol/rat.day had no effect, probably due to the degradation of the hormone when administered this way. We also compared the effects of bPTH-(1-84) when administered by either daily sc injections or continuous infusion. Continuous infusion of bPTH-(1-84) resulted in an increased apposition rate. Using a morphometric technique, we also found an increase in both formation and resorption surfaces and a net decrease in the trabecular bone volume in this group. Daily injection of the hormone caused an increase in the bone apposition rate, accompanied by an increase in the formation surface without an increase in the resorption surface. This resulted in a net increase in trabecular bone volume. The results thus suggest that the resorptive effects of bPTH-(1-84) can be separated from the effects of the hormone on the apposition rate.

Animals↗
PubMed1982

Activation and clearance of a hormonogen, triglycyl-oxytocin, in the conscious dog.

Triglycyl-oxytocin (TGOT) and oxytocin (OT) were administered iv and sc to conscious dogs and the plasma concentrations of these peptides determined simultaneously by RIA and bioassay. Constant iv infusions (1 h) at 23 pmol/kg/min produced plateau levels of 1.1 and 1.6 pmol/ml plasma for OT and TGOT respectively. Whilst the distribution space was similar for each peptide. TGOT persisted longer in the circulation (t1/2, for TGOT 6.6 min; for OT 4.2 min). Bioactive values for OT followed RIA values whether this peptide was given iv or sc. Although very little bioactivity was generated by iv infusions of TGOT, considerable amounts of bioactive OT were found in plasma after injection of TGOT subcutaneously. The hormonogen proved relatively resistant to oxytocinase, an enzyme that destroys OT rapidly. Our results indicate that TGOT is converted to OT in vivo and that its action as a hormonogen is more pronounced after sc than iv administration.

Animals↗
PubMed1982

A new bioassay for human growth hormone based on incorporation of labelled proline into skin.

An in-vitro bioassay for human growth hormone (hGH) has been developed, based on the dose-related enhancement of radioactivity in skin of hypophysectomized rats given daily s.c. injections of hGH and a single i.p. injection of labelled proline. The measured radioactivity, taken as the response, was shown to be independent of the site at which the skin was sampled. Valid dose-response relationships were obtained after as little as 3 days of treatment with GH. The assays by this method are shown to be more precise than the widely used weight-gain and tibial-width bioassays. Assays carried out gave an average index of precision of 0.036.

Animals↗
PubMed1982

Prolonged hypoglycemic effect in diabetic dogs due to subcutaneous administration of insulin in liposomes.

The biologic action of insulin entrapped in liposomes (phospholipid vesicles) has been investigated following subcutaneous injection to dogs made diabetic with a combination of alloxan and streptozotocin. The fats of the liposomally entrapped material was determined by injecting rats subcutaneously with either 125I-insulin or the labeled polysaccharide 14C-inulin, incorporated in liposomes labeled with 3H-cholesterol. Injection of liposome insulin (0.75 U/kg) to five diabetic dogs resulted in a mean (+/- SEM) blood glucose fall from 16.4 +/- 0.8 to 2.9 +/- 0.4 mmol/L. The glucose level had still not returned to baseline after 24 h and, correspondingly, immunoreactive insulin (IRI) could still be detected in frozen and thawed plasma 24 h after injection. In contrast, the hypoglycemic effect of the same dose of free insulin with or without empty liposomes virtually ended within 8 h and IRI levels returned to baseline by 3 h after injection. In experiments on rats with liposomally entrapped 125I-insulin or 14C-inulin the proportion of the injected dose of tracer recoverable by excision of the injection site remained constant after about 1 h and 70% of the dose was still fixed in subcutaneous tissue for at least 5 h thereafter. When the plasma collected 3 h after subcutaneous injection of labeled liposomes containing 125I-insulin was passed through a column of Sepharose 6B, 50-75% of the 125I-activity was found in the fractions associated with intact liposomes. One possibility for the persistence of the hypoglycemic effect and of measurable IRI following injection of liposome insulin could be the presence of intact liposomes in the circulation for many hours after adsorption had ceased.

Animals↗
PubMed1981

Sulfur-free parathyroid hormone analogues containing D-amino acids: biological properties in vitro and in vivo.

Three sulfur-free analogues of bovine parathyroid hormone (bPTH) containing D-amino acids were synthesized by the solid-phase method and their biological properties compared in an in vitro bioassay (rat renal adenylate cyclase assay), a receptor assay for parathyroid hormone (PTH) (canine renal membranes), and an in vivo bioassay (chick hypercalcemia assay). The analogue [Nle8,Nle18,D-Tyr34]-bPTH-(1-34)-amide, which was found to be more than 4 times as potent in vitro as unsubstituted PTH, is the most potent analogue of PTH yet synthesized. The enhanced potency was largely attributable to increased affinity for the PTH receptor. In vivo, however, this analogue was only one-third as potent as bPTH-(1-34). Cumulative evidence suggests that the nearly 15-fold decline in the relative potency when the compound was assayed in vivo is due to the substitution of norleucine for methionine. The other analogues, [D-Val2,Nle8,D-Tyr34]bPTH-(1-34)-amide and [D-Val2,Nle8,Nle18,D=Tyr34]bPTH-(2-34)-amide, were only weakly active in vitro and in vivo, indicating that substitution with D-amino acids at the NH2 terminus of PTH causes markedly diminished receptor affinity. In fact, the placement of a D-amino acid at the NH2 terminus is more deleterious to biological activity than is omission of amino acids at positions 1 and 2.

Adenylyl Cyclases↗
PubMed1981

Characterization of seasonal changes in prolactin and growth hormone cells in the hypophyses of white-tailed deer (Odocoileus borealis) by ultrastructural and immunocytochemical techniques.

Prolactin and GH cells were identified in thin sections taken from the adenohypophyses of adult male (6) and female (8) white-tailed deer, collected during all seasons of the year, by locating portions of the same cells in adjacent thick plastic sections immunostained for either PRL or GH. Growth hormone cells were round to ovoid in shape and filled with dense spherical secretory granules which ranged in size from 168 to 682 nm, with a mean diameter of 367 +/- 18 nm (X +/- SD) in the 14 glands studied. No apparent seasonal changes were evident in the ultrastructural appearance of GH cells. Prolactin cells were small and angular in shape during the winter months and contained only a few small secretory granules. By early summer, they wee markedly hypertrophied, round to oval in shape, and densely packed with large spherical secretory granules. The increase in size of PRL secretory granules was most prominent in pregnant females in May, when their mean diameter was approximately double than in midwinter. The ultrastructural appearance of PRL cells in September was similar to that of cells studied in March. The size distribution of PRL secretory granules overlapped that of the GH granules, ranging from 114 to 564 nm, and the mean diameter was 246 +/- 53 nm, calculated from all 14 individual glands. Our observations suggest that the synthesis and secretion of PRL are closely linked to photoperiodic changes in this species, and they demonstrate the necessity of using specific immunocytochemical techniques in the ultrastructural identification of pituitary acidophils, and of specifying the time of year and location (specifies photoperiod) in studies concerning PRL physiology, particularly when dealing with wild animal populations.

Animals↗
PubMed1981

Continuous subcutaneous insulin infusion: comparison of plasma insulin profiles after infusion or bolus injection of the mealtime dose.

To help optimize meal-time blood glucose control in diabetic patients by continuous subcutaneous insulin infusion we have studied plasma insulin profiles in six normal subjects, suppressing endogenous insulin secretion with somatostatin. Insulin was administered subcutaneously either as a bolus or by high-rate infusion. Mean infusion profiles were similar on the two occasions, with peak levels at 75 and 90 min respectively, and a linear decline to 34% and 36% of peak concentrations at 5 h. Bolus injection resulted in a faster rise in insulin concentration, more consistent with physiological requirements. It is concluded that bolus delivery would be similar in effect while mechanically simpler to achieve than infusion, when part of a dual rate subcutaneous infusion system. The dose should be given 30 min before meals, if peak insulin concentrations are to be coincident with those found physiologically. Insulin concentrations remain high in the post-absorptive phase.

Adult↗
PubMed1981

Estrogen receptor-like macromolecule in MtTW15 rat pituitary tumors: effects of antiestrogens.

To understand how estradiol-17 beta (E2) influences MtTW15 rat pituitary tumor function, we have evaluated the cytosolic E2 binding properties of tumors derived from control and steroid treated host animals. Specific E2 binding (approximately 3 pmoles/g tumor) was observed in all groups and was steroid responsive. The E2 binding macromolecule migrated to 7S following sucrose density gradient sedimentation and was specific for estrogenic steroids. Saturation analysis of E2 binding revealed a high affinity interaction (Kd = 5.5 +/- 0.5 x 10(-10) M). Furthermore, E2 binding was temperature-sensitive and degraded by trypsin. Thus, the MtTW15 tumor contains an estrogen receptor. Accordingly, the effects of 4 antiestrogenic drugs on tumor estrogen-receptor levels, tumor growth and hormone production were evaluated. In general, these drugs reduced cytosolic estrogen receptor levels, promoted tumor growth and increased tumor growth-hormone production. It is suggested that these compounds can exert both estrogen agonist and antagonist properties in MtTW15 tumors.

Animals↗
PubMed1981

Autoradiographic comparison of growth factors: influence of growth hormone and somatomedin B on patterns of proline incorporation.

Patterns of incorporation of 14C proline have been compared by whole body autoradiography to study the action of growth factors, infused for 1 week to hypophysectomized rats by subcutaneously implanted minipumps. Human growth hormone (hGH) caused dose-related increases in the width of the tibial epiphyseal cartilage and obvious weight gain, whereas only at 640 micrograms/week did Somatomedin B have a barely significant effect on these two parameters. Samples of tissues showing significant proline uptake by autoradiography were burned for direct measurement of 14C content. Both hGH (80-160 micrograms/week) and SMB (160-640 micrograms/week) significantly enhanced proline uptake in skin, tibia, liver and kidney. Whereas the Somatomedin was less active than hGH on skin it showed a greater effect on bone, significantly exceeding the apparently maximal response to hGH. The autoradiographic technique can be used not only to compare different growth factors but also to study the growth process by use of appropriate tracers.

Animals↗
PubMed1981

The effect of pinealectomy on seasonal changes in prolactin secretion in the white-tailed deer (Odocoileus virginianus borealis).

Surgery was performed on four buck and four doe 9-month-old white-tailed deer in March of 1978. Pinealectomy was performed on two deer of each sex, and the remaining animals received sham operations. At monthly intervals over the following year, baseline and TRH-stimulated (200 microgram/deer, iv bolus) serum PRL was measured over a 3-h period by RIA. Baseline PRL levels in sham-operated animals followed a circannual pattern, with peak levels occurring in June (74-237 ng/ml for does; 34-193 ng/ml for bucks) and lowest levels occurring in midwinter (0.41-0.44 ng/ml for does; 0.10-0.13 ng/ml for bucks). Pituitary responsivity to TRH followed the same patterns as that seen for basal PRL levels in sham-operated deer, with the highest peak serum PRL responses in June (198-568 ng/ml for does; 190-395 ng/ml for bucks) and the lowest peaks seen in midwinter (0.27-0.80 ng/ml for dose; 0.29-2.62 ng/ml for bucks). Pinealectomy appeared to abolish the circannual basal serum PRL rhythms in bucks, while this rhythm was maintained in does. Basal PRL levels in pinealectomized bucks ranged from 0.36-10.5 ng/ml, and basal levels in pinealectomized does ranged from 0.10-29.4 ng/ml. The greatest peak PRL response to TRH in pinealectomized deer was seen in August (41.2-93.4 ng/ml for does; 32.0-40.5 ng/ml for bucks), while the lowest peak response occurred in January (0.33-11.0 ng/ml for does; 0.50-17.0 ng/ml for bucks). Both sexes retained a degree of seasonality in their pituitary responsiveness to TRH, but the magnitude of the response in pinealectomized deer was greatly diminished in the summer months and increased in the winter months. Our results show that pinealectomy alters the naturally occurring photoperiod-linked seasonal profile of serum PRL in white-tailed deer and the associated pituitary responsiveness to TRH.

Animals↗
PubMed1981

Glucocorticoid-like actions of medroxyprogesterone acetate upon MtTW15 rat mammosomatotropic pituitary tumors.

We have shown recently that the MtTW15 experimental rat pituitary tumor responds to medroxyprogesterone acetate (MPA) by increasing GH production. In this study, using a single saturating dose assay and dextran-coated charcoal separation, the data indicate that the MtTW15 tumor contains cytosolic MPA binding sites. The concentration of sites (approximately 4 pmol/g tumor) was similar for tumors derived from male or female hosts but was significantly reduced in tumors from MPA- or estradiol-treated rats. The MPA binder sedimented to 4S on low salt sucrose density gradients and was of high affinity (Kd = 5.0 +/- 0.4 X 10(-9) M). However, binding specificity studies showed glucocorticoids to be better ligands than MPA. MtTw15 tumors were also analyzed for cytosolic progestin ([3H]R5020) and glucocorticoid ([3H]dexamethasone) binding sites. Only low levels of an estradiol-inducible progestin binder were found. In contrast, the concentration of glucocorticoid binding sites was similar to that observed for MPA, approximately 4 pmol/g tumor, as were the characteristics of the binding, i.e. 5.1 +/- 0.2S, Kd = 4.1 +/- 0.5 X 10(-9) M, and similar binding specificities. Both MPA and estradiol treatment of tumor-bearing rats decreased the concentration of both MPA and glucocorticoid binding sites. Furthermore, studies to determine if glucocorticoids would mimic the in vivo effect of MPA upon MtTW15 tumors, i.e. altered tumor hormone production, supported such a hypothesis. We conclude that the MtTW15 rat pituitary tumor contains a cytosolic glucocorticoid receptor and that MPA can interact with this receptor. The glucocorticoid receptor may be responsible for the MPA- and glucocorticoid-induced alterations in GH production.

Animals↗
PubMed1981

Dissociation of parathyroid hormone bioactivity and immunoreactivity in pseudohypoparathyroidism type I.

Circulating levels of parathyroid hormone (PTH) in six patients with pseudohypoparathyroidism type I (PSPI) have been measured by two immunoassays and by cytochemical bioassay and compared with measurements in normal subjects and patients with clinically defined hyper- and hypoparathyroidism. In all PSPI patients, the levels of immunoreactive PTH were in the hyperparathyroid range, whereas the bioactive levels were either in the normal or close to the normal range. In one patient from whom the dihydrotachysterol therapy was withdrawn, both immunoreactive and bioactive PTH concentrations increased. The finding that the PTH measured by RIA in these PSPI patients may have reduced biological activity may explain some of the clinical findings of hypoparathyroidism in this syndrome.

Adult↗
PubMed1981

Suckling in the guinea-pig: the simultaneous release of oxytocin and neurophysin.

The release of oxytocin and neurophysin during suckling has been studied in conscious unrestrained guinea-pigs. After prior separation, mothers and litters were allowed to suckle for a period of 10 min, and the weight gain of the litter recorded as an index of milk transfer. Maternal blood samples were obtained without disturbance through previously implanted intravenous cannulae and neurophysin and oxytocin determined on unextracted plasma by specific and sensitive radioimmunoassays. In 82 out of 118 experiments the young gained weight during suckling (1.6 +/- 0.1 (S.E.M.) g/pup) and this was associated with large rises in both oxytocin and neurophysin concentrations in plasma (mean concentrations: oxytocin 65.4 fmol/ml, neurophysin 360 fmol/ml). Where serial samples were taken, oxytocin and neurophysin showed a rapid rise and fall in concentration closely associated with the occurrence of milk ejection as judged by the behaviour of the litter. The present results provide the first direct evidence of a spurt release of both oxytocin and neurophysin measured simultaneously during milk ejection. The conscious lactating guinea-pig thus provides a useful laboratory model in which to study hormone release during milk ejection.

Animals↗