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Biomedical subjects

T R Fraser

Publications and source records attributed to T R Fraser.

At least 37 records · Page 2Linked to original sources
PubMed1975

The role of calcium in insulin action. III. Calcium distribution in fat cells; its kinetics and the effects of adrenaline, insulin and procaine-HCl.

The effects of adrenaline, insulin and procaine-HCl on Ca distribution in intact fat cells and on Ca binding to fat cell ghost membranes have been investigated. 1. Fat cells incubated in 45Ca containing media till isotopic equilibrium indicated that the exchangeable Ca in these cells averages 25.7 +/-3.2nmol/mg protein, which represents approximately 9.8% of their ttotal Ca content. 2. Perifusion of 45Ca prelabelled fat cells gave washout curves whose analysis conformed with three kinetically distinct Ca pools (Fig. 1). The fast exchangeable pool (Compartment A) had an efflux rate constant of 0.193 +/-0. 013 min.-. The release of Ca from the second and thrid pools (Compartments B and C) was much slower with efflux rate constants of 0.032 +/-0.0018 min.-1 and 0.0042 +/- 0.0006 min.-1 respectively. Changing the Ca concentration in the perifusing medium modified the initial fast phase and its rate constant, while added dinitrophenol (DNP) inhibited the efflux rate from the later compartments...

Adipose Tissue↗
PubMed1975

The role of calcium in insulin action. IV. Mechanism of insulin resistance in adipose tissue of obese (ob/ob) mice and old Wistar rats.

The in-vitro antilipolytic response to insulin and procaine hydrochloride by adipose tissue from young rats (150 - 180 g) and lean mice has been compared with that from aged Wistar rats (600 g) and obese (ob/ob) hyperglycaemic mice. 1. The adipose tissue from the obese mice showed diminished responsiveness to insulin and to procaine hydrochloride. Response to these agents, however, was restored by prewashing the tissue, suggesting that the apparent resistance in this tissue reflected saturation of the insulin receptors to endogenous insulin. 2. In adipose tissue of old Wistar rats the antilipolytic effect of insulin was also impaired, but this was not restored after extensive washing. Unlike adipose tissue ghosts prepared from young rats, insulin did not decrease the binding of calcium to ghost membrane preparations from old rats. Neither did insulin inhibit the adrenaline stimulated 45 calcium efflux from perifused isolated fat cells prepared from old rats. These results suggest that the insulin response of fat cells from old rats is impaired because of a defect either in their insulin receptors or in their post-receptor responses. 3. Procaine-hydrochloride, however, when added to the medium perifusing fat cells of these old rats inhibited the adrenaline stimulated lipolysis, reduced the Ca efflux and decreased the binding of Ca to fat cell ghosts; as it did with similar preparations of young rats. Thus the cells from old rats still show full post-receptor responsiveness to an insulin-like stimulus, provided the stimulus for such a response is given at a point beyond the insulin receptor itself. The results suggest that the insulin resistance observed in old rat fat cells may be related to some by deficiency in the insulin receptors, possibly due to their lower replacement with age.

Adipose Tissue↗
PubMed1975

Production and storage of (125-I) thyroxine and (125-I) triiodothyronine of high specific activity.

High specific activity [125-I] triiodothyronine and [125-I] thyroxine have been produced regularly by the chloramine T radioiodination method. Simultaneous production of [125-I] triiodothyronine and [125-I] thyroxine is usual when diiodothyronine or triiodothyronine are employed as the starting materials. Specific activities reached vary with the starting compound (diiodothyronine, triiodothyronine, thyroxine) used, as both substitution and, less readily, exchange of iodine atoms take place. Starting with diiodothyronine specific activities of approximately 2400 and 5200 Ci/g were achieved for [125-I]triidothyronine and [125I] thyroxine, respectively, and, similarly, specific activities of approximately 1200 and 4000 Ci/g for [125I] triiodothyronine and [125I]-thyroxine, respectively, were reached when triiodothyronine was the starting material. [125-I] Triiodoacetic acid and [125I] tetraiodoacetic acid have been produced in the same way from triiodoacetic acid. By column chromatography on Sephadex G-25 (fine), eluting with alkaline phosphate buffer, good separation of the radioiodinated products has been readily achieved. Studies on the stability of the radioiodinated hormones showed that 50% methanol, ethanol, propanol and propylene glycol were all equivalent as preserving agents and, further, that the stability of the radioiodinated hormones was linearly related to the concentration of these preserving agents.

Chromatography, Gel↗
PubMed1975

Plasma-lipids and glucose/insulin relationship in non-insulin-requiring diabetics with and without retinopathy.

Serum-lipid concentrations and their relationship to blood-glucose and serum-insulin were examined in non-insulin-requiring diabetics, 62 with and 45 without retinopathy. The age, sex-body-weight, and duration of known diabetes was comparable in the two groups. All were treated by diet only or diet and oral hypoglycaemic agents. Patients with retinopathy had higher fasting serumtriglyceride and serum--cholesterol levels than those without. Compared with a non-diabetic population, significantly more diabetics with retinopathy had raised derum-lipids. The lipid concentrations did not correlate with body-weight, serum-thyroid-stimulating-hormone levels, renal involvement, or fasting blood-sugar. While the blood-sugar concentrations were similiar in the two groups the absolute insulin increment and the relative insulin response to a 50 g. oral glucose load were significantly lower in those with retinopathy than in those without. The impairment of insulin response correlated significantly with the frequency of hyperlipidaemia. It is suggested that insulin deficiency with secondary hyperlipidaemia is characteristic of diabetic patients with retinopathy.

Adult↗
PubMed1975

Prolactin studies in "functionless" pituitary tumours.

Hyperprolactinaemia was found in all 17 women and in one out of six men who presented with hypogonadism and a radiologically enlarged sella turcica but no other clinical endocrine dysfunction. Some of the women also had galactorrhoea. The greater the level of hyperprolactinaemia in these 18 patients the larger their sellae turcica except in two patients with unusual features. The sella turcica was usually asymmetrically enlarged and there was rearly an upward extension of tumour, though the sella floor often showed some erosion on tomography. An oral dose of bromocriptine suppressed the hyperprolactinaemia in mose patients at the same rate as in normal post-partum women. Nine of the 18 patients with hyperprolactinaemia had low basal luteinizing hormone (LH) levels. The LH responsiveness to 100 mug of LH-releasing hormone (LHRH) was tested in 12, and eight showed subnormal values. Of eight biopsy specimens obtained four showed acidophil granules on light microscopy, and in five granules of various sizes were seen on electron microscopy.

Adult↗
PubMed1975

Mode of insulin action.

A unifying hypothesis is proposed for the mechanism of insulin action in adipose tissue. Insulin both induces displacement of Ca++ from a membrane-bound pool and inhibits efflux of the ion, thereby facilitating a rise in intracellular free Ca++ concentration. The former effect could enhance the transport of substrates and ions into the cell, while the latter modulates the activity of some intracellular enzymes to stimulate glycogenesis, lipogenesis, and decrease lipolysis and glycogenolysis. The calcium ion might act as the missing second messenger for insulin action.

Adenosine Triphosphate↗
PubMed1975

The effect of yttrium-90 implantation on endocrine function and visual fields in patients with "functionless" pituitary tumors, with biopsy and radiological findings.

Thirty patients with symptoms from "functionless" pituitary tumours were treated by yttrium-90 implants, and we report here the effects on symptoms, pituitary function and visual fields. On biopsy, about a third of the tumours showed some hormone granules. In the sixteen fully assessed at 1 year, pituitary function was improved in 25%, unchanged in 62-5%, and reduced in 12-5%. Improvement was confined to those in whom gonadotrophin secretion was the only function impaired pre-implant. Visual field defects were present pre-implant in ten patients (twenty eyes); at 1 year post-implant these defects had lessened in 80% and deteriorated in only 5% of eyes. Subsequently, within 5 years of the implant the field defects had worsened or recurred in four patients, all with initially extensive suprasellar projection; further treatment was then given. Remineralization of the sella was seen after implantation in seven cases, with reduction in fossa size in five. Thus pituitary implantation appears to be a practicable and reasonably simple procedure suitable for the treatment of most cases of "functionless" pituitary tumour. The "supressive" doses of irradiation used are adequate to shrink most tumours without loss of pituitary function.

Adenoma↗
PubMed1975

Thyrotrophin and prolactin responsiveness to thyrotrophin releasing hormone in Cushing's disease.

Serum thyrotrophin response to thyrotrophin releasing hormone was impaired in all of eight subjects with untreated Cushing's disease; while all of six similar subjects tested after adequate treatment by a pituitary implant of 198Au then showed a normal response. In all five of the untreated patients studied, the serum prolactin response to TRH was normal. Thus chronically excessive cortisol levels as seen in Cushing's disease inhibit pituitary TSH responsiveness to TRH without affecting the prolactin response to TRH. Evidently the release of TSH and of prolactin by TRH are governed by independent mechanisms.

Cushing Syndrome↗
PubMed1975

Hormonal responses to a first course of clomiphene citrate in women with amenorrhoea.

The hormonal criteria of a "normal" or "ovulatory" response, and three grades of subnormal anovulatory responses, were defined during a first course of treatment with clomiphene citrate in twenty patients with amenorrhoea for which no organic cause could be found. The hormonal responses were estimated by frequent serum measurements and by the menstrual response. Seven patients had a normal or ovulatory response with a late rise of serum progesterone and subsequent menses. Their serum luteinizing hormone (LH) and oestradiol (E2) responses were greater than in spontaneous menstrual cycles. Five patients gave only partial responses, with menstruation and no prior rise of progesterone, Their serum LH and E2 responses were generally lower than in the normal group but had the same pattern except for an absence of the luteal phase rise in E2. Five patients who did not menstruate showed smaller and more variable responses. The remaining five showed no hormonal responses. The second and third groups had ovulatory responses on subsequent clomiphene courses, whereas no improvement was shown by the last group. The serum E2 responses offered the most sensitive index of the responsiveness to clomiphene. Response values in our normal group suggested that higher progesterone levels need to be reached after clomiphene administration than in spontaneous cycles for ovulation to be inferred. The serum prolactin showed no consistent response during the clomiphene test; three patients with moderately raised basal prolactin levels had "normal" responses.

Amenorrhea↗
PubMed1975

A study of the effect of bromocriptine on serum oestradiol, prolactin, and follicle stimulating hormone levels in puerperal women.

Nine normal women were examined in the first 11 days of the puerperium. Serum prolactin, oestradiol and follicle simulating hormone (FSH) levels were measured and the FSH response to 100 mug of intravenously administered follicle stimulating hormone/lutenizing hormone-releasing hormone (LH/FSH-RH) was assessed on day 1 post partum in five subjects and on days 4 (two subjects), 6 and 7 post partum in the other four subjects. Bromocriptine therapy was given to six of these women and four to seven days after the start of such therapy, when prolactin levels had fallen to normal non-pregnant levels, these women were retested. Before bromocriptine treatment, the basal FSH levels were unmeasurable in six and low in one other of the nine subjects. After bromocriptine treatment, the basal FSH levels were measurable in four out of six patients and were higher than in the untreated patients (P less than 0-01). The FSH response to LH/FSH-RH was unmeasurable in eight out of nine before treatment, which is less than the response seen in 26 normal men and women (P less than 0-01). There was also no discernible FSH response to LH/FSH-RH after treatment with bromocriptine. Before treatment with bromocriptine, the serum prolactin levels were elevated in all nine women but were within the normal range for non-pregnant women after three days of bromocriptine therapy. Thus postpartum gonadotrophin suppression seemed to depend on high prolactin levels and at least part of the antigonadotrophic action of prolactin seemed to be at pituitary level.

Bromocriptine↗
PubMed1975

Gel filtration of human urinary immunoreactive luteinizing hormone.

In human urinary concentrates and also in a urinary gonadotrophin standard (2nd IRP-HMG), gel-filtration analysis revealed three main peaks of immunoassayable luteinizing hormone (LH). A similar analysis of LH extracted from human pituitaries showed most of the activity in a peak of larger molecular weight, and only minor fractions in the positions of the urinary peaks. In an extract of normal human serum, analyss showed only one similar peak of large molecular weight, which also emerged before the urinary peaks. During an i.v. infusion of pituitary LH into normal men, the urinary LH activity increased but was still found only in the same three peaks on gel filtration, and all were of a molecular weight smaller than that of the infused material; but a higher proportion of the urinary LH was found in the earliest of these peaks compared with that found before infusion. Conversely, 20-35 h after the i.v. infusion, there was a slightly higher proportion of LH activity in the third peak of smallest molecular weight. These findings suggest that the urinary immunoassayable LH, which is found in three peaks of different molecular weights, is derived from the pituitary or serum LH of higher molecular weight. The changes in the proportions of larger or smaller molecular weight fractions in the urine during and after LH infusion suggest that the earliest peak may be disaggregated serum LH, while the last or smallest molecular weight peak may comprise metabolites of LH.

Adrenocorticotropic Hormone↗
PubMed1974

DDAVP in treatment of vasopressin-sensitive diabetes insipidus.

In 11 patients with vasopressin-sensitive diabetes insipidus the effectiveness of the vasopressin analogue 1-desamino-8-D-arginine vasopressin (DDAVP) for controlling diabetes insipidus has been compared with that of lysine vasopressin. DDAVP in equivalent intravenous dosage has been found to be at least as potent and to have a more prolonged action, lasting 13-22 hours instead of 1-2 hours. Twice-daily intranasal DDAVP effected satisfactory control in all these patients, without side effects, and all the patients preferred this to their previous treatment. Single daily intramuscular injections of DDAVP were found to offer excellent control for any subject unable to manage intranasal administration.

Administration, Intranasal↗