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Biomedical subjects

S Atkinson

Publications and source records attributed to S Atkinson.

At least 55 records · Page 3Linked to original sources

Steroid production and hCG binding by ram-induced ovarian follicles in seasonally anoestrous ewes.

The introduction of rams to a group of previously isolated anoestrous ewes has been shown to stimulate ovarian follicular development and ovulation. The present experiment was carried out to determine the ability of follicles arising from this ram stimulus to produce steroids and bind hCG. Seasonally anoestrous Southdown ewes were exposed to rams for 24 h, 40 h, 3 days, 10 days or 20 days before ovariectomy. Steroid production and the concentration of hCG binding sites in follicles dissected from the ovaries were measured in vitro. The presence of a ram caused ovulation and enhanced oestradiol production by follicles, but had little effect on total androgen production or the number of hCG binding sites present in the follicles when compared to follicles from anoestrous ewes. The oestradiol concentrations in large follicles were not as high as in preovulatory follicles from cyclic ewes reported in other studies. Follicles continued to develop through the ram contact period and when incubated after 40 h and 10 days of ram contact produced high levels of progesterone, indicating partial luteinization, although the corpora lutea (CL) resulting from the induced ovulations regressed prematurely. We suggest that the lack of hCG binding sites in ram-induced follicles may be the cause of poor luteinization and suboptimal development of luteal tissue after induced ovulation in ewes during seasonal anoestrus.

Anestrus

Demonstration of significant epidermal growth factor activity in murine thyroid tissue.

Epidermal growth factor (EGF) was first isolated from the mouse submaxillary gland (SMG) which remains its only known site of synthesis. Earlier work suggests that EGF may be implicated in the regulation of thyroid cell growth and proliferation. Moreover, thyroid hormones increase the EGF content of mouse SMG and mimic the maturational effects associated with EGF. The aim of this study was therefore to determine whether the mouse thyroid gland is a site of EGF production. Thyroid and submaxillary glands were homogenized in Tris-HCl, the EGF content was measured by a homologous radioimmunoassay (RIA) and receptor-binding activity assessed in a radioreceptor assay. Epidermal growth factor was readily detectable in each thyroid extract. Dilution curves were parallel to the standard curve. Values obtained for right and left lobes of thyroid were in excellent agreement (r = 0.997, P less than 0.001). The intrathyroidal EGF concentration obtained by RIA was 26.1 +/- 6.0 (S.E.M.) ng/mg protein (n = 40); values obtained by the receptor assay were slightly lower but correlated closely (r = 0.828, P less than 0.01). Assay of homogenates prepared at the same time from the submaxillary glands of these mice showed that thyroidal EGF was not correlated with EGF content in the SMG. These findings indicate that EGF, both biologically active and immunoreactive, is readily detectable in the mouse thyroid and that the thyroid gland is a probable site of EGF synthesis. The methodology provides a model for further studies of the regulation of EGF production and its significance in relation to thyroid disease.

Animals

Homologous radioimmunoassay for epidermal growth factor in human saliva.

Epidermal growth factor (EGF) is a small polypeptide with potent mitogenic activity. Its synthesis by mouse submaxillary gland is stimulated by certain hormones. To assess its physiological significance in man, we have developed a homologous radioimmunoassay for human epidermal growth factor (hEGF) in saliva. A satisfactory standard curve was readily obtained using either buffer or peptide-free saliva. The mean IC50 was 436 +/- 200 pM (mean +/- SD) and sensitivity approximately 35 pM. The mean normal salivary hEGF in 63 males was 314.6 +/- 21.7 pM (+/- SEM) and 354 +/- 27.8 pM in 48 females. The difference between the means of the sexes was not significant. Assays of aliquots stored under different conditions showed hEGF in saliva to be stable and the method reproducible. Salivary hEGF secretion did not suggest diurnal rhythmicity and was unrelated to meals.

Adult

Ram-induced growth of ovarian follicles and gonadotrophin inhibition in anoestrous ewes.

Southdown ewes in mid-seasonal anoestrus were exposed to rams for 0 h (control group), 2 h, 24 h, 40 h, 3 days, 10 days or 20 days. Serial blood samples were then taken to determine LH and FSH levels. Ewes with greater than 24 h ram exposure were ovariectomized immediately after bleeding, and all follicles greater than 1 mm diameter were dissected from the ovaries and measured. LH basal concentrations and pulse frequency increased significantly within 2 h of ram introduction, but by 24 h fell, and then remained low. FSH concentrations fell within 2 h of ram introduction and remained low. Control group ewes (isolated) had no follicles greater than 4 mm diameter, whereas all ewes exposed to rams had large follicles, with CL or preovulatory follicles present at 40 h after ram introduction. Ram introduction was also associated with follicle recruitment (antrum formation to less than 2 mm). Follicular recruitment and development to the large follicle stage therefore occurred during a period of low plasma gonadotrophin levels and suppressed LH pulsing.

Anestrus

Ophthalmopathic immunoglobulin in patients with Graves' ophthalmopathy.

An IgG which binds specifically to retro-orbital antigen has been detected in patients with Graves' ophthalmopathy. By means of an assay which detects ophthalmopathic immunoglobulin (OIg) in patients' serum with an antigen prepared from porcine retro-orbital muscle, levels of OIg above the normal reference range were found in 21 of 33 (64%) patients with active untreated ophthalmopathy, in 3 of 12 (25%) with active disease already receiving steroid treatment, and in 3 of 18 (16%) with longstanding inactive eye disease. OIg was found in only 1 of 22 thyroid patients without eye disease. There was no correlation of OIg with thyrotropin-binding-inhibiting immunoglobulin nor with thyroid microsomal antibody, and there was no clear association with thyroglobulin antibody. Ophthalmopathy seems to be distinct from Graves' hyperthyroidism and the autoimmune response is directed to retro-orbital antigens.

Animals

A specific IgG in Graves' ophthalmopathy and its relation to retro-orbital and thyroid autoimmunity.

An IgG (ophthalmopathic immunoglobulin) that binds to retro-orbital antigen was identified in serum from patients with active Graves' ophthalmopathy, and its nature and specificity were investigated. Dose related binding of this immunoglobulin to retro-orbital antigens prepared from guinea pig harderian gland or porcine eye muscle was found, which could be abolished by prior incubation with antigen. The immunoglobulin did not bind to thyroid membranes, thyroid microsomes, or thyroglobulin or interact with liver, skeletal muscle, or fat membranes. Serum with high activity of thyrotrophin binding inhibiting immunoglobulin did not react with retro-orbital antigen, and this activity was not affected by preincubation of the serum with retro-orbital antigen. Thyroid stimulating hormone was also without effect on retro-orbital antigen. It is concluded that Graves' ophthalmopathy is associated with a specific ophthalmopathic immunoglobulin that reacts with retro-orbital antigen as distinct from thyroid antigens, and that the autoimmune response is directed towards retro-orbital antigens. This suggests that the ophthalmopathy is an entity distinct from autoimmune thyroid disease.

Adult

Evidence that thyroid-stimulating antibody is produced in the thyroid gland.

The hyperthyroidism in Graves' disease results from the action of thyroid-stimulating antibodies (TSAb). The thyroid gland in Graves' disease shows diffuse lymphocytic infiltration, and after removal of the gland antibody titres usually decline and patients go into remission. It is postulated that the lymphocytes in the thyroid may be an important site of TSAb production. 10 patients with Graves' disease and 8 patients with other thyroid disorders were studied. Blood was taken during operation, but before thyroid mobilisation, from the thyroid vein and simultaneously from a peripheral vein. In patients with Graves' disease the concentration of TSAb activity in the thyroid vein was much greater than that in the peripheral vein. TSAb was not detected in either peripheral vein or thyroid vein samples in the other patients. The increase in TSAb concentration in the thyroid vein indicates production of antibodies by lymphocytes within the thyroid and could explain why removal of the thyroid results in disappearance of TSAb from the circulation.

Adult

Screening for refractive errors in 6-9 month old infants by photorefraction.

The method of isotropic photorefraction has been used in a trial of refractive screening of 6-9 month old infants. Data are presented on the calibration of the method against retinoscopic measurements and its reliability. In photorefractive screening of 1096 infants under cyclopentolate cycloplegia 5% were found to be hypermetropic (over +3.5 D), 4.5% myopic, and 1.3% anisometropic (over 1 D). These refractive errors were confirmed on retinoscopic follow-up (with the exception of a few anisometropes). Follow-up of controls shows that one small refractive error was missed in 52 infants. We conclude that photorefraction is a valid and practical screening technique. Longitudinal study of infants with refractive errors will assess the value of early detection, in particular for prediction and prevention of strabismus.

Adult

Specific epidermal growth factor receptors on porcine thyroid cell membranes.

Specific saturable receptors for epidermal growth factor (EGF) of high affinity (Ka 1.7 X 10(9) M-1) have been demonstrated on porcine thyroid membranes. Optimal conditions for EGF binding have been determined. TSH and other peptide hormones do not inhibit the binding of 125I-EGF and EGF does not inhibit 125I-TSH binding to thyroid membranes. The results suggest that EGF may be involved in the regulation of thyroid follicular cell growth and function.

Animals

The assay of Graves' immunoglobulins: a comparison of different methods.

A multiplicity of techniques has arisen for the measurement of the immunoglobulins specifically associated with Graves' hyperthyroidism, which has led to difficulty in assessing the clinical significance of these immunoglobulins. In this study of untreated toxic Graves' disease we have taken two assays (LATS protector and thyrotrophin binding inhibiting immunoglobulin, TBII) which depend upon the measurement of binding to thyroid cell membranes, and correlated them with a bioassay which measures as the index of activity the biologically relevant end point of T3 secretion from thyroid tissue. The frequency of positive responses obtained with each method was similar to that of previous studies; combining the results a positive response was found in 100%. No significant correlation was found between any of these three assays. T3 to assess which method relates most closely to circulating thyroid hormone levels in vivo. A highly significant correlation was obtained for TSAb measured by T3 secretion with both total serum T3 and total serum T4 levels. A positive correlation was also found for LATS protector, but not for TBII. We conclude that although these assays are specific for Graves' immunoglobulins, they are measuring closely related but not identical immunoglobulin activities.

Adult

Spastic diplegia among children of low and normal birthweight.

Data from a population-based Cerebral Palsy Register in Western Australia were analysed for children born between 1956 and 1975, and low birthweight (LBW) and normal birthweight (NBW) infants were compared. Control populations of similar birthweight to the cases were available from Western Australia live births. The incidence of spastic diplegia among LBW infants was higher than among those of NBW. The relative risk for LBW infants increased from 12- to 26-fold between 1961 and 1975, and those who previously would have died were surviving to be more severely disabled, both physically and intellectually. For LBW infants the risk of spastic diplegia increased both with increasing maternal age and with birth order; for NBW infants birth order was of main importance. LBW singletons, NBW twins and those born in rural hospitals had increased risk of spastic diplegia. More antenatal problems were seen in the LBW group, whereas the NBW group had higher rates of perinatal problems. Thus the groups may differ aetiologically, the LBW group having a greater likelihood of being damaged in utero, whereas the NBW group may have become brain-damaged as a result of traumatic deliveries.

Australia

Effect of radioiodine on stimulatory activity of Graves' immunoglobulins.

The effects of 131I therapy on the activity of thyroid stimulating antibody (TSAb) and thyrotrophin binding inhibiting immunoglobulin (TBII) in nineteen patients with Graves' disease have been studied. Prior to 131I administration TSAb was detected in 84%, and TBII in 68% of patients. Following 131I administration TSAb and TBII were detectable in 100% of patients. The elevation 3 months after treatment of the means of both the TSAb and TBII indices for the group of nineteen patients was highly significant compared with pre treatment values. All the patients went into remission during the course of the study and the TSAb index declined in all patients, becoming undetectable in eleven; TBII also declined in most patients but remained detectable in thirteen. The study furthermore afforded the opportunity for a direct comparison of binding with stimulatory activity. These results show that after 131I therapy for Graves' hyperthyroidism there is a transient increase in TSAb as well as TBII, followed by a decline, and that the measurement of binding and stimulatory activities are in good general agreement.

Antibodies

The stimulation of thyroid hormone secretion in vitro by thyroid-stimulating antibodies.

A new simple technique is described for the in vitro assay of thyroid-stimulating antibody (TSAb) in serum. Thyroid slices are incubated with serum in two-compartmental dialysis pot, followed by measurement of the thyroid hormone concentration in the dialysis fluid by RIA. Heat-inactivated normal serum applied directly to the tissue has no effect on the basal level of response. A dose-dependent relationship is demonstrated for both TSH and TSAb. Serum from patients with untreated Graves' hyperthyroidism is clearly shown to stimulate thyroid hormone secretion. Porcine thyroid tissue has been used and responds well to TSAb. This technique not only has the advantage of simple methodology, but also reflects the biological activity of TSAb. Therefore it will prove useful for further studies of the significance of TSAb and the pathogenesis of Graves' disease.

Animals

Effects of septal lesions on shock thresholds in weanling male and female rats.

Twenty-four-day old weanling male and female rats were either lesioned in the septal area, gonadectomized, lesioned and gonadectomized, or untreated. Tests for reactivity to electric shock were conducted at 26 and at 40 days of age. Neither males nor females showed any effect of the lesions are measured by flinch and jump thresholds to electric shock immediately following surgery; both male and female lesioned groups showed a significant lowering of thresholds when tested at 40 days of age. The effects of septal lesions on response to electric shock were dissociated from the effects on hyperemotionality measured over the same period of time after the lesions, and appeared to have their effect independent of the sex or hormonal condition of the animals.

Animals