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Biomedical subjects

J A Parsons

Publications and source records attributed to J A Parsons.

At least 73 records · Page 4Linked to original sources

Suckling in the guinea-pig: the effects of passive immunization with an antiserum to oxytocin.

Lactating guinea-pigs were passively immunized with an antiserum to oxytocin of high titre, specificity and avidity. Single i.v. injections of 0.1-0.4 ml antiserum produced high titres which decayed slowly (half-life congruent to 7 days). Passively administered antiserum was effective in vivo; the clearance of exogenous oxytocin from plasma was greatly slowed in immunized animals. Passive immunization with 0.4 ml antiserum reduced milk transfer to the litter during suckling episodes of 10 min, and overall litter growth rates were significantly decreased. Non-immune serum was without effect. Plasma neurophysin levels showed the same large rises during suckling in immunized animals, indicating that neurohypophysial activation was unimpaired. Despite the presence of high titres of antiserum, some milk transfer still occurred at milk ejection. In-vitro experiments showed that more than 25% of oxytocin remained free 20s after mixing with plasma taken from passively immunized animals. It is probable that the antiserum in the circulation was unable to bind all the oxytocin released from the posterior pituitary gland before it reached the mammary gland.

Animals↗

Precurrent self-prompting operants in children: "Remembering".

IN EXPERIMENT I, ONE OF THREE FORMS OF COLLATERAL BEHAVIOR WAS TRAINED: Differential collateral behavior specific in form to one of two discriminative stimuli; Common collateral behavior of a single form regardless of the stimulus; or Nondifferential collateral behavior of either form regardless of the stimulus. Children were next given a short-delay matching-to-sample task in which the discriminative stimuli served as samples, and the children's previously trained collateral behavior terminated the delay and presented the comparison stimuli. Subjects engaging in sample-specific collateral behavior immediately acquired matching. Subjects engaging in sample-nonspecific collateral behavior failed to acquire matching or did so gradually. In Experiment II the minimal delay in the matching task was varied in a mixed sequence, first with collateral behavior required, and then with collateral behavior prohibited. When emitting collateral behavior Common and Nondifferential subjects showed delay-related decrements in matching while Differential subjects did not. When not emitting collateral behavior all subjects showed delay-related decrements in matching. Common and Nondifferential subjects matched more accurately when prohibited from emitting collateral behavior. Differential subjects matched more accurately when emitting collateral behavior. The results accord with Skinner's (1953, 1968) analysis of precurrent operants.

Journal Article↗

Effects of 17 beta-estradiol and medroxyprogesterone acetate upon MtTW15 mammosomatotropic pituitary tumor growth and hormone production in male and female rats.

The purpose of this study was to characterize the effects of two functionally diverse steroids, 17 beta-estradiol and medroxyprogesterone acetate (MPA), on MtTW15 rat mammosomatotropic pituitary tumor growth and hormone production. Steroid responsiveness, as well as the hormonally autonomous nature of the tumor, was studied by treating both male and female tumor-bearing rats for 7 weeks with weekly injections of either 17 beta-estradiol (600 ng/g body weight/week) or MPA (200 microgram/g body weight/week) and, subsequently, comparing both the tumor weights and the in vivo production of growth hormone (GH) and prolactin (PRL) among the treatment groups. Large tumors (6 to 20 gm) were obtained in all treatment groups, indicating hormonal autonomy; however, tumors were markedly smaller, on the average, in untreated males an ovariectomized females. Treatment of such rats with 17 beta-estradiol stimulated tumor growth. Radioimmunoassay of tumor and serum GH and PRL levels in all treatment groups indicated the following: (a) tumors from untreated male or female hosts did not favor the production of one hormone over the other to any great extent; (b) MPA, however, promoted significant increases (p less than 0.05) in GH production in both male and female tumor-bearing rats while having little effect on the production of PRL; and (c) 17 beta-estradiol significantly inhibited (p less than 0.05) GH production and promoted PRL production by tumors borne by either sex. Selected studies utilizing multiple doses of MPA (1 to 500 microgram per gm body weight per week) and 17 beta-estradiol (10 to 800 ng per gm body weight per week) were accomplished and demonstrated that hormone production can be influenced in a dose-related manner. These results indicated that the estrogen-induced MtTW15 rat pituitary tumor is hormonally autonomous, yet divergently responsive to two different classes of steroidal compounds, thus making this tumor line an appropriate model for the study of hormonally responsive pituitary tumor cells.

Animals↗

Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial.

After baseline studies, 21 patients with osteoporosis were treated with human parathyroid hormone fragment (PTH 1-34) given as once-daily subcutaneous injections for 6-24 months. The dose used did not cause hypercalcaemia even in the first few hours after injection. Calcium and phosphate balances improved in some patients, but there was no significant improvement in the group values. There were, however, substantial increases in iliac trabecular bone volume: the mean increase, confirmed by repeat blind measurements, was 70% above mean baseline volume. The new bone was histologically normal. Those patients who had the largest increases in 47Ca-kinetic and histomorphometric indices of new bone formation showed the greatest increases in trabecular bone volume, suggesting that treatment with human parathyroid hormone fragment caused a dissociation between formation and resorption rates that was confined to trabecular bone. Since vertebrae are four-fifths composed of trabecular bone, this hormone fragment may prove useful in treating patients with the crush fracture syndrome.

Aged↗

Functional classification of cell types in the growth hormone- and prolactin-secreting rat MtTW mammosomatotropic tumor with ultrastructural immunocytochemistry.

The aim of this study was to identify the neoplastic endocrine cells which contain growth hormone (GH) and prolactin (PRL), in the MtTW15 mammosomatotropic tumor, with ultrastructural immunocytochemistry. We used tumors recovered after 5 to 11 weeks of tumor development, from normal (untreated) rats and from rats treated with the progestin medroxyprogesterone acetate (MPA)--a stimulator of GH secretion in these tumors. Immunocytochemical staining was done with the peroxidase-antiperoxidase technique on ultrathin sections of tumor that had been fixed in glutaraldehyde and postfixed on osmium tetroxide. Immunospecific staining for PRL was found over small (150 nm) secretion granules, whereas staining for GH was deposited on the larger secretion granules (250 nm). Tumors from MPA-treated rats contained profuse numbers of neoplastic cells with large, GH-positive granules. Immunocytochemical staining for GH and PRL was also found in crinophagic, lysosome-like inclusions, particularly in cells that contained many secretion granules. The results support the hypothesis that GH and PRL are produced by separate neoplastic endocrine cell types in the MtTW15 mammosomatotropic tumor, and demonstrate the value of ultrastructural immunocytochemical analysis for functional classification of cell types in chromophobic pituitary adenomas.

Animals↗

Seasonal changes in prolactin and growth hormone cells in the hypophyses of white-tailed deer (Odocoileus virginianus borealis) studied by light microscopic immunocytochemistry and radioimmunoassay.

Numerous investigators have shown a relationship between basal serum prolactin (PRL) levels and photoperiod in domestic ungulates, and we have shown recently that a similar seasonal baseline serum PRL profile exists in both sexes of a captive but free-breeding population of white-tailed deer. In order to localize and describe the distribution and possible seasonal changes of PRL and growth hormone (GH) cells in the adenohypophyses of deer, we have used antisera raised against ovine PRL and bovine GH and the unlabeled antibody enzyme technique, in conjunction with point counting morphometry. In addition, we have measured seasonal changes in pituitary PRL concentrations in this same population, using a heterologous application of a recently developed homologous radioimmunoassay (RIA) for ovine PRL. Our results show that GH and PRL cells comprise two morphologically separate and immunologically distinct populations. Growth hormone cells were distributed evenly throughout the gland, except in the zona tuberalis, and males had a slightly greater volume density of immunoreactive GH than females; however, there were no differences between sexes in the average size of these cells, and little seasonal change was observed in these cell populations. In contrast to GH cells, the volume density of PRL cells, the size of PRL cells, and the pituitary concentration of RIA--measurable PRL all showed marked seasonal changes in deer of both sexes. These changes were well correlated with one another and with previously reported changes in basal serum levels (in these animals), in that they all reached zenith during midsummer, and nadir in midwinter. Our results demonstrate the necessity of reporting the time of year and latitude (to specify photoperiod) in studies concerning PRL cell physiology, particularly when dealing with any wild animal population.

Animals↗

Heterogeneity of the MtTw15 mammosomatotropic tumor. II. Characterization of parenchymal cells by superimposition immunocytochemistry and electron microscopy.

Large MtTw15 tumors, which secrete growth hormone (GH) and prolactin (PRL), are composed of ovoid, elongated, and angular cells which demonstrated interdigitating processes and junctional complexes. The majority of the cells were essentially agranular, but two types of granulated cells were identifiable. One class of granulated cells contained moderate to sparse populations of round dense-cored granules measuring up to 250 nm in diameter. Rod-shaped to filamentous mitochondria with an electron-dense matrix were characteristic of a second class of granulated cells with plemorphic granules of various sizes and electron densities. Images of exocytotic release of the round dense-cored granules were frequently seen, but were not observed with the pleomorphic granules, many of which were judged to be lysosomes. Superimposition immunocytochemistry revealed hormones only in the granulated cells with round to ovoid granules. Morphometry indicated that hormone specific subpopulations of tumor cells can be identified since PRL secretory granules were significantly smaller than GH secretory granules (149 +/- 6 nm for PRL versus 221 +/- 9 nm for GH, P less than 0.001). The vast majority of immunopositive cells contained only GH or PRL, but a few were observed containing both hormones. Ovoid to irregular-shaped nuclei, large lipid inclusions, numerous free ribosomes and polyribosomes, moderate development of the rough endoplasmic reticulum, and prominent Golig profiles were characteristics of all cell types. Irrespective of the presence or absence of cytoplasmic granular elements, particles resembling viruses were encountered in many tumor cells, and these frequently appeared to be budding into the cisternae of the endoplasmic reticulum.

Animals↗

Matched glucose responses to insulin administered subcutaneously and intravenously. Evidence for subcutaneous inactivation of insulin.

A new technique of programmed intravenous insulin infusion at a series of decreasing rates has been used to imitate the magnitude and time course of biological responses obtained by the subcutaneous route. Groups of normal rats prepared with indwelling venous cannulae were injected subcutaneously with soluble porcine insulin, 0.4 U/kg. The pattern of the resulting hypoglycaemic response was subsequently matched by a 2-hour intravenous insulin infusion at rates decreasing stepwise from 0.3 to 0.05 U kg-1h-1. The total amount of insulin infused intravenously was only 50% of that required subcutaneously. In addition, subcutaneous or intravenous infusions of insulin at 0.05 U kg-1h-1 were given to two groups of rats from the same batch. When both infusions were continued until plateau responses were reached, a significantly greater lowering of plasma glucose was caused by the intravenous route. These results suggest that when insulin is given subcutaneously significant inactivation of the insulin occurs at or near the injection site.

Animals↗

An homologous and sensitive radioimmunoassay for the synthetic amino-terminal (1-34) fragment of human parathyroid hormone: application to the clearance of this peptide administered in vivo.

The synthetic 1-34 amino-terminal fragment of human parathyroid hormone (hPTH 1-34) is undergoing multicentre clinical trials to assess its long term therapeutic potential in the treatment of osteoporosis. An homologous radioimmunoassay (reagents prepared from the synthetic hPTH 1-34 peptide) has been developed to monitor the pharmacokinetics of hPTH 1-34 in man and in a dog model. The assay is rugged, sensitive (detection limit 1.75 x 10(-11) moles/litre) and precise (coefficient of variation 6%). Three different ampouled preparations of the native intact hPTH 1-84, of different degrees of purity (approximately 3%-90% pure) gave complete log dose response curves parallel to that of the ampouled synthetic hPTH 1-34 peptide, and were equipotent on a molar basis. Native intact bovine PTH 1-84 showed an incomplete non-parallel displacement curve; there was no recognition of synthetic hPTH 44-68 and 53-84 peptides. Preliminary application of the assay to the determination of the plasma disappearance of hPTH 1-34 in man and dog gave half-times (t1/2) of 3-8 minutes for a first exponential component and 12-18 minutes for the second; in the dog, metabolic clearance rate was calculated to be 9ml/kg/minute and the distribution space 160ml/kg.

Amino Acids↗

Long-term continuous subcutaneous insulin infusion in diabetics at home.

6 insulin-requiring diabetics were treated at home with continuous, long-term, dual-rate subcutaneous insulin infusion (CSII) by means of a portable syringe pump. The duration of infusion was 48--111 days. Patients were initially stabilised on CSII in hospital and then allowed home, where capillary-blood glucose control was monitored by the patients with glucose-oxidase reagent strips. Patients diluted and changed their own insulin for the pump, adjusting the dose according to the control achieved. Mean (+/- SD) blood-glucose values ranged from 4.8 +/- 1.6 to 7.5 +/- 1.6 mmol/l. In 1 longstanding diabetic insulin requirements fell from 92 U/day to about 35 U/day on CSII. 2 newly diagnosed juvenile-onset diabetics were also infused: in 1 patient requirements fell to zero after 48 days and in the other the dose fell to 14 J/day after 51 days of CSII. No cannula-site infection or significant palpable lipodystrophy was experienced. Patients treated with "open-loop" systems have little or no insulin reserve: potential loss of control--for example, during intercurrent illness-demands careful metabolic monitoring and prompt correction.

Adolescent↗

Continuous subcutaneous insulin infusion: improved blood-glucose and intermediary-metabolite control in diabetics.

Blood-levels of glucose and the major intermediary metabolites, lactate, pyruvate, 3-hydroxybutyrate, and alanine, were measured in 7 insulin-dependent diabetics during 24 h of continuous subcutaneous insulin infusion (C.S.I.I.) from a portable dual-rate syringe pump. Results were compared with metabolic profiles during the patients' conventional insulin treatment and with those of 17 non-diabetics. The mean 24 h plasma-glucose during C.S.I.I. was not significantly different from that in non-diabetics. During infusion blood concentrations of lactate, pyruvate, 3-hydroxybutyrate, and alanine were also close to those in the non-diabetic state. Thus, C.S.I.I. provides strict control not only of blood-glucose but also of major metabolites, an essential prerequisite for investigating the influence of good metabolic control on diabetic microangiography.

Adolescent↗

Transdermal uptake of a peptide hormone: inhibition by calcitonin eardrops of induced osteolysis in guinea-pig ossicles.

In view of a recent proposal that calcitonin injections may arrest the bony pathology of otosclerosis, we have tested the possibility of obtaining locally effective concentrations by giving salmon calcitonin in eardrops. Osteolysis of guinea-pig ossicles induced by injecting parathyroid hormone shortly before explantation was markedly inhibited by 3 days prior instillation of the calcitonin in an aqueous vehicle or in dimethyl sulphoxide, but not by a solution in propylene carbonate.

Animals↗

Continuous subcutaneous insulin infusion:good blood glucose control for up to 4 days.

Six insulin-dependent diabetics were studied on their conventional insulin treatment and during continuous, dual-rate, subcutaneous insulin infusion for periods of up to 4 days. Dabetic control, as assessed by mean plasma glucose, range of plasma glucose values, M-value or range of M-values was improved significantly in 5 patients (mean +/- SD plasma glucose concentration on final infusion day 6.9 +/- 1.3 mmol/l, versus 11.3 +/- 3.2 mmol/l on conventional treatment). Once a suitable insulin dose was established blood glucose control could be maintained by continuous subcutaneous insulin infusion using the same daily infusion rate without frequent adjustment. In some case this was less than the daily dose on the conventional treatment. However, glycaemic control in one "brittle" diabetic, with unpredictable swings in blood glucose on her normal regimen, was not improved by continuous subcutaneous insulin infusion. During the period tested there was no sepsis at the cannula implantation site and patients did not find the system uncomfortable or unduly inconvenient.

Adult↗

Evidence that protease inhibitors reduce the degradation of parathyroid hormone and calcitonin injected subcutaneously.

1 Agents known to delay absorption from a subcutaneous site were tested in chicks for their ability to prolong the hypercalcaemic response to parathyroid hormone (PTH). 2 Polyvinylpyrrolidone was found to enhance the response but gelatine greatly reduced the 2 h hypercalcaemia. 3 The reduction by gelatine was reversed when the protease inhibitor aprotinin was added to the injection vehicle, and hypercalcaemia then persisted for more than 8 h. 4 Of other protease inhibitors studied, epsilon-aminocaproic acid was also found to enhance the hypercalcaemic response to subcutaneous PTH and its fragments but, unlike aprotinin, it was ineffective in the presence of gelatine. 5 By radioimmunoassay and bioassay respectively, it was confirmed that aprotinin raised circulating levels of PTH and also of another peptide hormone, calcitonin, injected subcutaneously. 6 Addition of calcium to the solutions injected subcutaneously abolished the hypercalcaemic response to PTH while injection of calcium and PTH simultaneously but at separate sites left the response unaltered. 7 The two protease inhibitors, epsilon-aminocaproic acid and aprotinin, each restored the response to subcutaneous PTH despite the presence of calcium at the injection site. 8 It was concluded that protease inhibitors injected subcutaneously with PTH and calcitonin in the chick reduced the rate of degradation of these hormones and that the proteases responsible for hormone degradation at the subcutaneous injection site may be released or activated by calcium ions.

Animals↗