Biomedical subjects

J S Jenkins

Publications and source records attributed to J S Jenkins.

At least 55 records · Page 3Linked to original sources

PubMed1990

Interaction of vasopressin and oxytocin with human breast carcinoma cells.

The arginine vasopressin and oxytocin content of normal and cancerous human breast tissue were measured using radioimmunoassay. Both peptides were present in amounts greater than that found in the circulation, but no difference between normal and malignant tissues was found. Binding of [3H]oxytocin and [3H]vasopressin were characterized in human breast carcinoma cells (MCF7 cells). Binding of both hormones to MCF7 cells was specific and saturable, the vasopressin receptor found to be of the V1 subtype. Scatchard analyses of the data were linear, indicating a single high affinity, low capacity binding site for each hormone (vasopressin: KD = 47.4 +/- 1.6 nmol/liter, Bmax = 27,300 +/- 6,500 sites/cell; oxytocin: KD = 51.3 +/- 0.4 nmol/liter, Bmax = 87,000 +/- 4,000 sites/cell). The effects of vasopressin and oxytocin on the growth of MCF7 cells were assessed using protein accumulation and cell numbers. Vasopressin at 10-1000 pmol/liter was mitogenic for MCF7 cells, but higher doses (10 nmol/liter) were growth inhibitory. Oxytocin was also mitogenic for MCF7 cells but to a lesser extent than vasopressin. In conclusion, we suggest that vasopressin and possibly oxytocin may be important modulators of the growth of some human breast carcinomas.

Arginine Vasopressin↗

PubMed1990

The effect of oxytocin infusion on adenohypophyseal function in man.

The responses of the adenohypophyseal hormones adrenocorticotrophin (ACTH), growth hormone (GH), thyroid stimulating hormone (TSH), prolactin, luteinizing hormone (LH) and follicle stimulating hormone (FSH) to sub-maximal doses of hypothalamic releasing factors were studied in six lean male volunteers (age 23-35 years) with and without infusions of oxytocin (OXT). OXT infusion (mean plasma concentration 133.6 +/- 2.6 pmol/l) completely inhibited the plasma ACTH responses to corticotrophin releasing hormone (CRH) (saline, peak increment ACTH 1.61 +/- 0.75 pmol/l; OXT, peak increment ACTH - 0.04 +/- 0.28 pmol/l; P less than 0.05). OXT infusion had no significant effect on the GH response to growth hormone releasing hormone (GHRH), the TSH and prolactin responses to thyrotrophin releasing hormone (thyroliberin, TRH) or the LH and FSH responses to gonadotrophin releasing hormone (luteoliberin, GnRH). The data support a role for OXT in the modulation of ACTH secretion in man.

Adrenocorticotropic Hormone↗

PubMed1990

Basic fibroblast growth factor in human pituitary tumours.

Immunoreactive (ir) basic fibroblast growth factor (FGF) has been measured in normal human pituitary glands and in 41 pituitary tumours of various types using a radioimmunoassay. Normal pituitary glands contained ir basic FGF ranging from 29.4 to 355 fmol/mg wet weight whereas 87.5% of pituitary tumours contained amounts of the growth factor which were less than normal. There was no relationship between the type of tumour and the FGF content. Normal and tumorous pituitary FGF had an affinity for heparin which was similar to that of basic FGF. Gel column chromatography revealed that the pituitary ir FGF was present mainly as high molecular weight forms, with only a small proportion as the basic 146 amino-acid peptide. Because of our previous observation that basic FGF inhibits the growth of human pituitary tumour cells, it is suggested that the reduction in basic FGF of many pituitary tumours may favour the stimulation of pituitary growth.

Adenoma↗

PubMed1990

The responses of arginine vasopressin and adrenocorticotrophin to nausea induced by ipecacuanha.

Ipecacuanha syrup induces emesis by an early peripheral (gastric irritant) action and a later central effect at the chemoreceptor trigger zone (CTZ). We have studied the responses of plasma AVP, ACTH and ACTH-precursors to early and late ipecacuanha-induced nausea in nine healthy male subjects. Symptom severity was assessed using a linear analogue scale. All subjects reported 'early' nausea (N1) with a latency of 16 +/- 2 min (mean +/- SEM) and eight subjects vomited. Six subjects experienced recurrent nausea (N2) (latency 106 +/- 10.4 min) of whom five also vomited. The interval between the cessation of N1 and the onset of N2 was 55 +/- 10.8 min (range 25-80 min). The severity of nausea at the onset of N1 or N2 was similar but the AVP and ACTH responses were highly variable. Thus, while mean plasma AVP concentrations increased during both symptom periods, in three subjects during N1 and in three subjects during N2 plasma AVP concentrations did not rise above the normal range, despite marked symptoms. No clear pattern of AVP response to distinguish early peripheral from late central ipecacuanha-induced emesis was demonstrated. Whilst mean plasma ACTH concentrations increased during both N1 and N2 there were no changes in mean plasma ACTH-precursor concentrations. Analysis of pooled data for N1 and N2 demonstrated direct correlations between the nausea score and the peak incremental plasma responses of either AVP or ACTH and, despite the variability, peak incremental concentrations of AVP and of ACTH were also correlated. The data indicate that there is no difference in the AVP responses to peripherally or centrally stimulated ipecacuanha-induced nausea.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1990

Premature coronary artery disease and the Prader-Willi syndrome.

A 28 year old woman with the Prader-Willi syndrome developed chest pain and loss of anterior R wave amplitude on the electrocardiogram. Cardiac catheterization demonstrated a severe proximal stenosis of the left anterior descending artery with delayed antegrade flow together with antero-apical akinesia consistent with myocardial infarction. Physicians involved in the management of patients with the Prader-Willi syndrome should be aware of this association with premature coronary artery disease.

Adult↗

PubMed1989

A programmable system for acquisition and reduction of respiratory physiological data.

A portable software package (TIDAL--Tools for Intelligent Data Acquisition in the Laboratory) for acquiring and analyzing respiratory physiological data is described. TIDAL supports flow-, volume-, and concentration-measuring devices, and any other instruments that produce linear analog outputs. The system allows users to specify the names and types of channels to be sampled, and the calculations involved in reducing samples to breath-to-breath values. The specification of channels and calculations is given in EDL, an Experiment Description Language designed for respiratory physiology. EDL comprises a set of internal functions (primitives) which can be combined into arbitrarily complex expressions. To simplify EDL programming, TIDAL includes a macro processor and a standard macro library; the library contains definitions for a wide variety of respiratory variables. Examples are inspiratory and expiratory times and total volumes, mean inspired and expired gas volumes and concentrations, and end-tidal concentrations. Variables that are derived from these primary data, such as respiratory quotient, are also easily specified. TIDAL is written entirely in the C programming language, with special attention to portable coding practices. The code is organized in a modular structure that eases porting to multiple hardware/compiler/operating system environments.

Expert Systems↗

PubMed1989

Recursive identification of lung parameters.

Determination of lung capacity (FRC) using insoluble gas washout or equilibrium methods is a common procedure in respiratory tests. The lung model can be extended to include multiple compartments with differing volumes and ventilation fractions. A discrete-time mathematical model of a multi-compartment lung was developed based on mass conservation laws of the gas exchange. To estimate the unknown parameters in the model from experimental data, a recursive prediction error algorithm was implemented. The design of the algorithm provides the capability to track time-varying parameters, such that the system can be monitored on-line. Determination of the model order may be as important as estimation of the parameters, especially in biological systems where little may be known about the structure. Two new criteria to distinguish between models of varying complexity, the 'minimum description length principle' and the 'accumulated prediction error', are illustrated. Theoretical studies show that these criteria yield consistent order estimates of the process. Simulations and experimental data confirm the feasibility of this approach for the estimation of lung parameters.

Algorithms↗

PubMed1989

An extended soluble gas exchange model for estimating pulmonary perfusion--I: Derivation and implementation.

A dynamic model for respiratory exchange of blood soluble gas is described. This model includes a general treatment of tidal breathing, an inhomogeneous lung comprising multiple distensible compartments, and nonlinearities due to multiple-gas effects. The motivation for this new model is the continuing interest in estimating pulmonary perfusion from measurements of respiratory soluble gas exchange. Numerical simulation can be employed to investigate the errors that result from simplifications made in the derivations of simpler models used for this purpose. Examples of such simplifications are the assumptions that ventilation is constant and unidirectional, and that multiple soluble gases can be independently modeled. These results can delimit the boundaries within which perfusion estimates can be considered reliable. An example demonstrating the model and its numerical solution is presented.

Models, Biological↗

PubMed1989

An extended soluble gas exchange model for estimating pulmonary perfusion--II: Simulation results.

The assumptions made in deriving models of soluble gas exchange used for continuous estimation of pulmonary perfusion are critically examined. Comparisons are made between estimation algorithms based on simple and more complex models. The more complex model includes a general treatment of tidal breathing, an inhomogeneous lung comprising multiple distensible compartments, and nonlinearities due to multiple-gas effects. The results show that sensitivity of perfusion estimates to errors inherent in simple linear models. These errors can invalidate the estimates under realistic physiological conditions. Concentration and multiple-gas effects, for example, can cause substantial estimation errors. Large ventilations relative to lung volume can also lead to errors. These simulations can be used to delimit the conditions under which the estimates can be considered reliable. A further set of simulations is used to assess the sensitivity of perfusion estimates to errors in the assumed values of unknown or approximately known model parameters. Inadequate specification of the compartmental structure of the lung (distributions of ventilation/perfusion and ventilation/volume) can cause large estimate errors. Precise estimates of lung tissue volume do not appear to be necessary. These results are important for the practical application of soluble gas methods for pulmonary perfusion determination. In both sets of simulations, it is shown that parameter estimate accuracy must be confirmed independently of goodness-of-fit criteria. Close agreement between predicted and observed end-tidal concentrations does not ensure accurate perfusion estimates.

Computer Simulation↗

PubMed1989

Hypothalamic disease in association with dysgenesis of the corpus callosum.

We describe two cases of dysgenesis of the corpus callosum demonstrated by magnetic resonance. The first patient presented with chronic hyponatraemia. Investigation demonstrated re-setting of the osmoreceptor and thirst centres. The calculated threshold for arginine vasopressin (AVP) release was reduced at 252 mosmol/kg while severe thirst was perceived at a plasma osmolality of 260 mosmol/kg. Insulin-induced hypoglycaemia produced an exaggerated AVP response. The second patient presented with hypothermia. The calculated threshold of AVP release was 296 mosmol/kg with increased sensitivity of AVP response to hypertonic saline. The plasma AVP response to insulin-induced hypoglycaemia was absent. Both cases had normal anterior pituitary function and psychological assessment showed a similar prefrontal defect. Specific tests of callosal function were normal. These cases illustrate the importance of undertaking complete neuroradiological assessment of cases of unexplained hypothalamic disease regardless of the age of presentation to avoid overlooking this rare congenital association.

Adolescent↗

PubMed1989

Oestradiol, vasoactive intestinal peptide and fibroblast growth factor in the growth of human pituitary tumour cells in vitro.

The growth of two human prolactin-secreting cell lines developed in our laboratory has been investigated in response to a number of factors. Oestrogen stimulated the synthesis of DNA and protein and increased prolactin secretion. Dexamethasone had the opposite effect to oestrogen. In the presence of serum, epidermal growth factor (EGF) inhibited cell growth at concentrations of 5 ng/ml. Known secretagogues of prolactin (vasoactive intestinal peptide (VIP), TRH, bombesin and neurotensin) were investigated for their action on cell growth but only VIP had a stimulatory effect. Two preparations of fibroblast growth factor (FGF) were studied. One form, derived from bovine pituitary glands, stimulated human pituitary cell growth. In contrast, another FGF, of the basic type (rFGF), was inhibitory to cell growth, increasing the time for cell doubling from 30 to 72 h. This inhibitory effect of rFGF was modified but not abolished by serum, oestradiol, platelet-derived growth factor or EGF. We conclude that bovine pituitary contains at least two fibroblast growth factors, both of which stimulate fibroblast cell growth, but one stimulates and the other inhibits human pituitary tumour cell growth.

Cell Line↗

PubMed1988

Vasoactive intestinal peptide stimulates glycolysis in pituitary tumours; 1H-NMR detection of lactate in vivo.

1H- and 31P-NMR spectroscopy has been applied to rats carrying implanted tumours in vivo, and used to observe simultaneous changes in intracellular pH (pHi) and lactate concentration during the stimulatory action of vasoactive intestinal polypeptide (VIP). A maximal decrease in pHi to a mean of 0.29 units below basal values was recorded. At the same time, 11 min after VIP, a maximal increase in tumour lactate was found, with a mean value of 150% of the basal concentration. The magnitude of these changes was compatible with in vitro measurements of basal lactate concentration and buffering capacity made on the same tumour line. It is concluded that VIP stimulates glycolysis by the tumour cells, resulting in an accumulation of lactate and a consequent fall in pHi.

Adenoma↗

PubMed1988

Differential release of vasopressin and oxytocin in response to abdominal vagal afferent stimulation or apomorphine in the ferret.

The aim of this study was to investigate whether direct afferent stimulation of the abdominal vagus could promote release of the neurohypophyseal hormones. The nucleus of the solitary tract is the major recipient of vagal afferent information, and this region of the brainstem may also be activated by stimulation of the area postrema. For this reason apomorphine, a D2 dopaminergic agonist which acts on the area postrema, and can evoke vasopressin secretion in man, was also investigated for its effect on vasopressin and oxytocin release. Our results show that vasopressin, but not oxytocin is released in vast amounts in response to electrical afferent stimulation of the abdominal vagus. Administration of apomorphine also evoked a massive vasopressin release with less marked effects on oxytocin. The possible functional implications of these results are discussed especially in the context of nausea and vomiting.

Abdomen↗

PubMed1988

An analogue of creatine increases TRH-stimulated prolactin secretion and phosphoinositide hydrolysis in rat pituitary tumor cells.

Prolactin (PRL)-secreting GH3 cells were grown, in vitro, with the creatine analogue beta-guanidinopropionic acid (GPA) added to the culture medium. After 5 days there was a small increase in basal and greatly increased thyrotropin-releasing hormone (TRH)-stimulated PRL secretion. The site of action of GPA is at the TRH-induced hydrolysis of phosphoinositides, since increased amounts of mono, bis and tris/tetrakis inositol phosphates were found in treated cells, while the PRL secretion induced by a phorbol ester or a calcium ionophore, treatments which mimic the second messages generated by inositol phospholipid hydrolysis, were not enhanced by GPA. The mechanism by which GPA increases phospholipase C activity has not been fully elucidated but may involve the activity of a controlling G protein.

Aminoquinolines↗

PubMed1988

Atrial natriuretic peptide inhibits osmolality-induced arginine vasopressin release in man.

1. Eight normal volunteers were infused with 5% saline (5 g of NaCl/100 ml) at a rate of 0.06 ml min-1 kg-1 for 120 min to increase plasma osmolality and plasma arginine vasopressin. Human atrial natriuretic peptide (alpha-hANP; 100 micrograms) or placebo was given in random order in a double-blind cross-over design for the last 20 min of the saline infusion. 2. Compared with the placebo infusion, atrial natriuretic peptide (ANP) produced a 43% greater sodium excretion and a 34% greater urinary volume in the subsequent hour. 3. Mean plasma immunoreactive ANP did not increase in response to changes in osmolality and rose to a peak of 118 pg/ml during the alpha-hANP infusion. alpha-hANP produced significant suppression of mean plasma arginine vasopressin over the 60 min after the infusions. 4. We conclude that ANP is not released in response to increased osmolality in vivo, and that it inhibits osmolality-induced arginine vasopressin release in man.

Adult↗

PubMed1988

The response of plasma oxytocin to surgical stress.

Recent evidence suggests that oxytocin (OXT) and arginine vasopressin (AVP) are involved in the response to stress. We have examined the changes in peripheral plasma OXT during abdominal surgery in eight patients (six males, two female; ages 60-82 years) undergoing hemicolectomy and compared the results with those for AVP to the same stimulus. There was no significant change in systolic blood pressure, blood haematocrit or plasma sodium, osmolality or glucose. AVP rose significantly after premedication (from 1.8 +/- 0.3 pmol/l to 5.5 +/- 2.3 pmol/l; P less than 0.05) but the greatest increase (to 35.8 +/- 6.6 pmol/l) occurred after gut manipulation. Plasma OXT concentrations fell slightly with premedication (from 5.7 +/- 2.0 pmol/l to 3.3 +/- 0.9 pmol/l; P less than 0.05) but rose markedly (to a peak of 33.5 +/- 11.4 pmol/l) after gut manipulation. The data support the concept that OXT like AVP may play a role in the neuroendocrine response to surgery. The stimulus to OXT release and its function remain to be determined.

Aged↗

PubMed1988

Responses of plasma oxytocin and arginine vasopressin to nausea induced by apomorphine and ipecacuanha.

Apomorphine, a centrally-acting emetic, was administered subcutaneously (50 micrograms/kg) to nine normal subjects (four male, five female; aged 22-36 years) and four patients with idiopathic diabetes insipidus (DI) (one male, three female; aged 24-49 years). In the normal subjects this stimulus caused nausea (and vomiting in seven of nine) with a latency of 9.5 +/- 0.9 min which was followed by a large increase in plasma arginine vasopressin (AVP) concentration (from 0.9 +/- 0.2 pmol/l to 249 +/- 104 pmol/l at 15 min after the onset of symptoms; mean +/- SEM, P less than 0.01). There was a small but significant increase in plasma oxytocin (OXT) concentration (from 1.6 +/- 0.4 pmol/l to 6.2 +/- 3.4 pmol/l; P less than 0.05). Mean arterial pressure (MAP) fell slightly (from 87 +/- 1.9 mm Hg to 71 +/- 4.4 mm Hg; P less than 0.05) 15 min after the onset of nausea; there was no change in blood haematocrit or plasma osmolality and sodium concentration. In the DI patients apomorphine produced nausea (with vomiting in three of four) with a latency of 10.0 +/- 1.4 min but failed to cause an increase in either plasma AVP or OXT. In the DI patients the fall in MAP did not reach statistical significance (83 +/- 4 mm Hg to 71 +/- 11 mm Hg); there was also no change in haematocrit, osmolality or sodium concentration. Ipecacuanha, an emetic with both peripheral and central actions, was administered orally to seven normal subjects (three male, four female; aged 22-36 years) six of whom also underwent apomorphine tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

The effect of oxytocin infusion on adenohypophysial and adrenal cortical responses to insulin-induced hypoglycaemia.

The responses of plasma adrenocorticotrophin (ACTH), cortisol, growth hormone (GH) and prolactin to insulin-induced hypoglycaemia were studied in six lean male subjects (age 22-29 years). Intravenous insulin tests were performed with and without oxytocin infusion. Blood sugar nadir occurred at the onset of symptoms (time S) with no significant differences between oxytocin and saline infusion. During the oxytocin infusion mean plasma oxytocin increased from 1.9 pmol/l to 138 pmol/l. Peak increase in plasma ACTH (oxytocin 266 +/- 54 ng/l; saline 281 +/- 43 ng/l, mean +/- SEM) was at S + 10 min while peak plasma cortisol (oxytocin 680 +/- 47 nmol/l: saline 656 +/- 40 nmol/l) was measured at S +/- 60 min, peak GH (oxytocin 96 +/- 17.8 mU/l; saline 106 +/- 18.6 mU/l) at S + 60 min and prolactin (oxytocin 1332 +/- 239 mU/l; saline 1242 +/- 273 mU/l) at S + 30 min. There were no significant differences in plasma concentrations of ACTH, cortisol, GH or prolactin between saline and oxytocin infusion. The results indicate that oxytocin has no effect on plasma ACTH, cortisol, GH and prolactin responses to insulin-induced hypoglycaemia. In particular they fail to support previous studies which suggested an inhibitory role for oxytocin in ACTH secretion.

Adrenal Cortex↗