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John R. David

ABSTRACT

This paper is a brief review of studies which demonstrate that lymphocyte mediators can activate macrophages in vitro. Macrophages which have been incubated in lymphocyte mediator-rich Sephadex fractions show changed morphology, metabolism and function. These changes include an increase in adherence to glass, ruffled membrane movement, phagocytosis of some particles, glucose oxidation through the hexose monophosphate shunt and an increase in the activity of a membrane enzyme, adenylate cyclase. Such mediator-activated macrophages show enhanced bacteriostasis and tumoricidal activity. In addition, studies describing the role of membrane sugars and esterases in the interaction of migration inhibition factor and macrophages are reviewed.

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John P. P. Tyler, John R. Newton and William P. Collins

ABSTRACT

The concentration of testosterone (ng/100 ml; mean ± sd) has been determined in peripheral venous plasma at 4 hourly intervals for 24 h from 9 non-pregnant women (39.8 ± 11.8) and 9 during late pregnancy (70 ± 32). In addition, the level of this hormone has been measured in samples of plasma removed daily (between 08.30 and 10.00 h) throughout 9 ovarian cycles (41.6 ± 11.8), and weekly from 10 women during gestation (57.6 ± 14.7).

The results show that there is considerable individual variation in both the concentration and pattern in serial samples over the respective time scales. The values of the arithmetic mean from non-pregnant subjects show that there is a tendency for the concentration to be lower between 20.00 and 04.00 h. However, the differences between the values at defined times over a 24 h period are not statistically significant. During the ovarian cycle 3 subjects had peak values during the peri-ovulatory phase, 2 in the luteal, 1 in the follicular and 3 showed no consistent pattern. There was no significant difference in values (40.9 ± 11.8, 41.9 ± 11.9 and 41.8 ± 11.9) for the 3 phases of the cycle. There is a significant rise in the concentration of plasma testosterone during pregnancy (P< 0.0005), but the pattern of the arithmetic mean is not related to the corresponding values for progesterone or oestradiol. During late pregnancy (34 weeks to term) there is a change in the nycterohemeral pattern, with the highest mean values occurring between 16.00 and 04.00 h. The results are discussed.

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John R. T. Coutts and M. C. Macnaugton

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John R. G. Challis and W. Bruce Currie

Abstract.

To understand the factors responsible for the increased pre-partum output of cortisol from the adrenal glands of the goat foetus, we measured changes in responsiveness to ACTH in vitro of dispersed adrenal cells from foetal goats of various gestational ages and we determined the output of cortisol (F) and corticosterone (B) in the presence of exogenous progesterone (P4) and 17α-hydroxyprogesterone (17α-OHP4). The increment in F output after ACTH increased 5-fold between day 100 and days 147 or 154 (term). This increase was not associated with changes in the ED50 for ACTH stimulation of F output. The basal and ACTH-stimulated output of F was similar to that of B at day 100 but 5–7 times greater than that of B at day 154. There was a significant effect of ACTH on P4 output on days 77, 100 and 147 but net utilization of P4 by the cells at term. The ratio of exogenous P4: 17α-OHP4 converted to F varied with gestation and increased from 0.11 at day 100 to 0.99 at day 154. Exogenous P4 was converted to B at all stages of pregnancy.

We conclude that in the goat there is an increase in the responsiveness of foetal adrenal cells to ACTH between day 100 of gestation and term. One factor associated with this change in adrenal responsiveness may be an increase in the activity of the enzyme 17α-hydroxylase.

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G. Stuart Wiberg, John R. Carter and Norman R. Stephenson

ABSTRACT

The mouse anoxia test was modified by using thiouracilized mice as the test animals. This permitted the simultaneous assessment of the goitre prevention response in the same mice. A comparison of the two parameters of thyroid activity revealed that the antigoitrogenic assay was more sensitive than the mouse anoxia technique and exhibited improved precision for the bioassay of thyroactive materials.

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G. Stuart Wiberg, John R. Carter and Norman R. Stephenson

ABSTRACT

It is well known that thiouracil and its derivatives not only block the synthesis of thyroid hormones but also alter the peripheral metabolism of thyroxine and triiodothyronine. Other goitrogens such as thiourea, thiocyanate and perchlorate do not have this extra-thyroidal effect. Hence the measurement of endogenous thyroid function namely »thyroxine secretion rate« as determined by the goitre-prevention response is affected by thiouracil but not presumably by the other goitrogens. The purpose of the present study was to see what effect different goitrogens had on the estimation of the relative potency of thyroid powder by the goitre prevention assay. The biological activities of pork and beef thyroid samples relative to a house standard were determined in a series of bioassays which used various goitrogens. Assays employing either thiouracil, thiourea, aminotriazole or perchlorate led to statistically equivalent potency estimates and indicated that the pork thyroid was significantly more active than the beef thyroid on the basis of the total iodine content. However, the slope of the log dose-response lines were significantly affected by the different goitrogens. When the relative potencies of pork and beef thyroid were computed on the basis of the triiodothyronine content, the three preparations had equivalent activity for each of the goitrogens. Thiocyanate proved to be toxic at the dose level employed and a valid assay was not possible.

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Akihiko Noguchi, Marvin R. Turnipseed, Karen Bentley and John W. Reynolds

Abstract.

The concentrations of mixed umbilical cord serum dehvdroepiandrosterone sulphate (DHAS) and total oestriol, were determined by radioimmunoassay in 301 infants. Of 280 infants born between 36 and 42 weeks of gestation, 260 were born by vaginal delivery and 20 were delivered by Caesarean (C-section). We found that there was a significant elevation of serum total oestriol (P < 0.005) after 35 weeks with no concomitant gestational change of DHAS. Within the vaginal delivery group steroid values were similar among infants born following spontaneous, oxytocin augmented, and oxytocin induced labour. Within the C-section delivery group, steroid values were similar in infants who experienced spontaneous labour and those who did not. However, DHAS level was significantly higher (P < 0.005) in the vaginal delivery group than in the C-section group. We postulate that the higher DHAS levels in the vaginal delivery group are the result of stress during the late first stage of labour or later.

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J. H. Lazarus, J. C. Kingswood and R. John

Abstract. Twenty hyperthyroid patients were randomly assigned in a double-blind fashion to receive either nadolol 80 mg/day or placebo for 2 weeks; all patients then took carbimazole as well from 2–6 weeks. Twenty-four hour Holter ECG recordings at 0, 2 and 6 weeks showed that nadolol reduced the mean maximum heart rate by 19.9% (P < 0.0005) at 2 weeks and by 30.3% (P < 0.0005) at 6 weeks compared to 5.2% (ns) and 18.3% (P < 0.0005) in patients taking placebo. There was no alteration of the normal circadian variation of heart rate by nadolol. The minimum heart rate before therapy was significantly correlated with FT4 (r = 0.52) and with FT3 (r = 0.44). The percentage of time per hour during which the heart rate was greater than 100 was reduced by 79% at week 2 by nadolol compared to 22% in the placebo group. At the 6 week point the placebo group still had a tachycardia (mean maximum heart rate 101.6 beats/min ± 15.2 sd) compared to the nadolol group (80.4 ± 7.7). Nadolol did not cause excessive bradycardia. It is effective in the early management of hyperthyroidism and should be given for at least the first 4–6 weeks.

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Janet M. Bryson, Aet Joasoo and John R. Turtle

ABSTRACT

A homologous receptor assay system using human thyroid membranes and 125I-labelledhuman TSH (hTSH) was used to study the effect of serum and serum fractions on the binding of [125I]hTSH to the membrane. Scatchard analysis showed a single population of binding sites for TSH. Gamma globulin fractions prepared from sera of patients with Graves disease were able to displace [125I]hTSH from the membrane to a greater extent than normal gamma globulin in 21 out of 45 cases. Increased displacement activity was seen in patients with thyroiditis, hot nodules and euthyroid eye disease but not in patients with toxic multinodular goitres. Further fractionation of the gamma globulin fraction showed that the stimulatory activity was not confined to the IgG fraction. Scatchard plots showed gamma globulin fractions decreased the number of receptor sites available for TSH binding but did not alter the affinity of the receptor for TSH. IgG fractions showed different slopes and intercepts and appeared to decrease the affinity of the receptor for TSH. LATS activity in human serum may be explained on the basis of these observations on the properties of the TSH receptor.

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John W. Bauman Jr., B. S. Chang and F. R. Hall

ABSTRACT

Using a method which permits bile collection relatively free from stress or trauma, we have studied bile flow in normal and hypophysectomized rats. Hypophysectomy was found to result in a sharply reduced bile flow which was not increased by small doses of corticosterone or of deoxycorticosterone. Adrenalectomy, previously reported to have a similar effect, was found not to reduce bile flow in either of the two strains of rats studied.