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Biomedical subjects

R L Himsworth

Publications and source records attributed to R L Himsworth.

At least 55 records · Page 3Linked to original sources
PubMed1982

Graves' disease: thyroid function and immunologic activity.

Patients with Graves' disease were studied for two years during and after a twelve-month course of treatment. Disease activity was determined by repeated measurements of thyroidal uptake of [99mTc]pertechnetate during tri-iodothyronine administration. These in-vivo measurements of thyroid stimulation were compared with the results of in-vitro assays of Graves, immunoglobulin (TSH binding inhibitory activity--TBIA). There was no correlation between the thyroid uptake and TBIA on diagnosis. Pertechnetate uptake and TBIA both declined during the twelve months of antithyroid therapy. TBIA was detectable in sera from 19 of the 27 patients at diagnosis; in 11 of these 19 patients there was a good correlation (p less than 0.05) throughout the course of their disease between the laboratory assay of the Graves, immunoglobulin and the thyroid uptake. Probability of recurrence can be assessed but sustained remission of Graves' disease after treatment cannot be predicted from either measurement alone or in combination.

Adult↗
PubMed1981

A comparative study of the binding of Graves' immunoglobulins by the patients own and other thyroid membranes.

Thyroid membrane preparations from six patients with active Graves' disease were tested in an assay which detects the thyroid interactive immunoglobulins of Graves' disease by their inhibition of binding of [125I]-thyroid stimulating hormone (TSH). With all preparations inhibition of binding of 125I-TSH by excess TSH could be demonstrated (specific binding). The patients' own immunoglobulins were assayed against their own thyroid membranes and against each other's under exactly comparable conditions. Inhibition of binding by IgGs from the patients varied between membrane preparations: with one preparation 5/6 IgGs were inhibitory but with another none were effective. Of the six patients, their own IgG inhibited binding of 125I-TSH to their own thyroid membrane preparation in only four instances, and when interaction did occur this did not reliably predict that the membrane preparation would interact with IgGs from other patients with Graves' disease. The selection of a membrane preparation for this assay cannot be made solely on ability to specifically bind TSH but the measure of the specific interaction with a Graves' IgG of proven potency must also be considered. Moreover, because of the variability between different membrane preparations, sequential clinical studies on individual patients, of the changes in concentration of Graves' IgG, must be performed using the same selected thyroid membrane preparation. We infer from these observations that the membrane structure in the vicinity of the TSH binding site is an important determinant of the interaction of Graves' IgGs with the TSH receptor, and that the configuration of this area is variable between individuals of the same species. The distinction between 'human-specific' and 'non-species-specific' thyroid stimulating antibodies is therefore probably not valid. The observation that the patient's own IgG was not often the most potent IgG inhibitor of binding of TSH also suggests that the Graves' IgG binding site is not identical or restricted to the TSH binding site; alternative explanations are discussed.

Adult↗
PubMed1981

Autoantibodies to thyroglobulin cross reacting with iodothyronines.

Serum thyroxine was consistently unmeasurable by radioimmunoassay in an elderly patient with myxoedema after successful treatment with oral thyroxine. Abnormal binding of thyroxine was suspected and shown to be due to the presence in serum of antibodies of the IgG variety. The characteristics of these antibodies with respect to their binding of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and human thyroglobulin (Tg) were systematically studied. Three preparations of Tg, and t4, T3 and rT3 were examined for their ability to compete with 125I-Tg, 125I-T4, 125I-T3 and 125I-rT3 for binding to the antibodies. For each tracer used the order of competitive efficiency was Tg greater than T4 greater than T3 greater than rT3. This provides for the first time direct evidence that iodothyronine reacting antibodies occurring in man are generated against Tg. All three iodothyronines were able to inhibit tracer binding of labelled iodothyronines completely, the order of effectiveness being T4 greater than T3 greater than rT3, suggesting antibodies with one type of binding site and that these were probably raised against a Tg sequence incorporating T4, although there was some evidence for the existence of a minor subpopulation of antibodies with higher specificity for T3. Complete displacement of labelled Tg by cold iodothyronines, however, was not possible. The experimental evidence suggests two classes of Tg antibodies, 70% of which were directed towards the T4 containing region, and 30% directed against other part(s) of the Tg molecule. Despite the presence of such Tg antibodies conventional haemagglutination tests of the patient's serum for Tg antibodies were negative.

Aged↗
PubMed1979

Interrelation of the pituitary-thyroid system at birth in man.

Samples of cord blood derived from 105 normal babies after uncomplicated deliveries were assayed for thyroxine (T4), tri-iodothyronine (T3), reverse tri-iodothyronine (rT3), thyroxine-binding globulin (TBG) and thyrotrophin (TSH). The values for T3, rT3 and TSH were log-normally distributed (geometric means 0.62 nmol/l, 3.28 nmol/l and 10.9 mu./l respectively) and those for T4 and TBG were normally distributed (means 126 nmol/l and 13.7 mg/l), The data were systematically analysed and no evidence was obtained to suggest that the concentration of TSH, which varied widely, was regulated by any of the thyroid hormones alone or in combination. There was a direct relation between the concentrations of T4 and T3 in the cord blood at birth but not between either of these and rT3. There is thus no evidence of a functional interdependence of the hypothalamic-pituitary-thyroid system in man at birth.

Fetal Blood↗
PubMed1978

A possible ACTH secreting tumour of the pituitary developing in a conventionally treated case of Addison's disease.

A patient with Addison's disease, treated with conventional corticosteroid therapy, developed endocrine and radiological features suggestive of an ACTH secreting pituitary tumour. The negative feedback control of ACTH secretion by the inhibitory effect of hydrocortisone was shown to be preserved although attenuated. Retiming and alteration of corticosteroid therapy reinforced this feedback control, without the need for supraphysiological amounts of steroid, and resulted in the regression of the endocrine disorder.

Addison Disease↗
PubMed1978

Reverse triiodothyronine, thyroid hormone, and thyrotrophin concentrations in placental cord blood.

Reverse triiodothyronine (rT3), triiodothyronine (T3), thyroxine (T4), thyroxine binding globulin (TBG), and thyrotrophin (TSH) were measured in sera from placental cord blood in an unselected series of 272 deliveries. In this series the concentrations of rT3 (mean 3.33 nmol/l, 95% confidence limits 1.6--7.0 nmol/l), were log normally distributed and did not overlap the adult normal range (0.11--0.44 nmol/l). There were no correlations between the cord blood concentrations of rT3, T3, T4, and TSH. The cord serum rT3 concentration was not influenced by maturity, birth-weight, or neonatal risk factors, whereas these factors did affect the concentrations of T3, T4, AND TBG. There is no arteriovenous rT3 concentration difference across the placenta, therefore the cord rT3 reflects the systemic rT3 concentration in the baby at birth. As rT3 in the neonate largely, if not entirely, derives from thyroxine from the fetal thyroid, measurement of the cord rT3 concentration may be a good immediate screening test for neonatal hypothyroidism.

Fetal Blood↗
PubMed1978

Regulation of thyrotrophin secretion by negative feedback of tri-iodothyronine on the hypothalamus.

Bilateral injections of tri-iodothyronine (T3, 2 ng in 2 microliter artificial cerebrospinal fluid, CSF) were made into the hypothalami of 15 hypothyroid rhesus monkeys (Macaca mulatta) prepared with chronically implanted intrahypothalamic cannulae. In 29 out of 96 such injections, the concentration of thyrotrophin (TSH) in the plasma fell rapidly by more than 30% and returned to the basal value over the succeeding 48 h, in 13 experiments the fall was 20-30% and in the remaining 54 experiments the level of TSH was unaltered. With [125I]T3, the extent of diffusion of T3 through the hypothalamus in these experiments was shown to be very limited. The hypothalamic injection sites were subsequently identified histologically and it was found that in those experiments in which the level of TSH in the plasma had fallen, T3 had been injected into either the dorsomedial nucleus or the lateral hypothalamic area extending into the preoptic region. Injection of artificial CSF alone into these areas of the hypothalamus did not affect the concentration of TSH. Direct intrapituitary injections of T3 (4 ng) resulted in small and inconstant changes in the concentration of TSH in the plasma and injections of T3 (400 ng) into the third ventricle were without any effect. These experiments demonstrate that T3 can rapidly inhibit the secretion of TSH by a direct action upon defined parts of the hypothalamus.

Animals↗
PubMed1978

The haematology of hyperthyroidism.

In an unselected series of 239 patients with uncomplicated hyperthyroidism the haemoglobin concentration was less than 12.0 g/dl in 37 of 207 women and below 13.0 g/dl in 9 of 32 men. Although some of these patients with a low level of haemoglobin were iron deficient, with a transferrin saturation less than 16 per cent, many were not. On treatment of hyperthyroidism the haemoglobin rose by an average of 0.5 g/dl in patients who had not been anaemic on diagnosis. A small fall in haemoglobin is therefore usual in hyperthyroidism and it may sometimes be sufficient to cause a mild degree of anaemia. The mean corpuscular volume (MCV) was decreased in hyperthyroid patients who had neither anaemia nor a reduced transferrin saturation. After treatment of hyperthyroidism the MCV rose in these patients by an average of 6 fl. A dimunition in MCV, even within the normal range, is an invariable concomitant of hyperthyroidism. The administration of thyroxine to excess does not, however, cause the same change in the MCV. On diagnosis of hyperthyroidism the prevalence of pernicious anaemia in this series of patients was 1.9 per cent. Gastric parietal cell antibodies were present in 15.4 per cent and thyroid microsomal antibodies in 49.5 per cent.

Adolescent↗
PubMed1977

'Big ACTH' and calcitonin in an ectopic hormone secreting tumour of the liver.

A young man presented with rapidly developing Cushing's syndrome which was due to the ectopic secretion of ACTH and beta-MSH-like material from hepatic tumour deposits, possibly originating from biliary radicals. This association of the ectopic ACTH syndrome has not previously been described. During the 22 month course of the illness the plasma immunoreactive ACTH and 'beta-MSH' concentrations rose by logarithmic progression. The plasma calcitonin concentration was also raised but did not change during the last 12 months. At any stage of the illness the plasma concentration of the ecotopically produced hormones was stable except that after hydrocortisone there were inconstant variations. During the course of the illness the ectopic ACTH became biologically less potent. This ineffectural ACTH was present in the plasma, in the tumour, and in the medium in which the tumour was cultured, in a large molecular weight form. This 'big ACTH' differed from the normal ACTH found in the patient's pituitary and from authentic ACTH in its immunochemical character: the C-terminal antigenic determinant (33-39 region of ACTH) was masked in the large molecular weight form but was uncovered after extraction in neutral buffer and this 'big ACTH' was more readily extracted from the tumour at pH 7.0. The tumour tissue also contained immunoreactive beta-MSH-like material and immunoreactive calcitonin which resembled calcitonin M chromatographically.

Adolescent↗
PubMed1977

Studies on a case of suppurative thyroiditis.

A patient with suppurative thyroiditis due to infection with Escherichia coli is described. Serial studies of thyroid function were performed. Before the abscess was drained there was no uptake of radio-iodine by the thyroid and there was some spillage of iodinated compounds from the gland. Post-operatively circulating thyroid hormone concentrations declined but were restored at four weeks. Thyroid uptake of radio-iodine was re-established two weeks after operation but there was little secretion of thyroxine at this time. Four weeks after operation the uptake of radio-iodine was greater than normal and thyroxine was being secreted. These changes in thyroid function were not associated with any significant rise in the plasma thyrotrophin concentration.

Aged↗
PubMed1977

Urinary steroid excretion by the squirrel monkey (Saimuri sciureus).

Urinary steroids and steroid conjugates were measured in the squirrel monkey (Saimuri sciureus). The principal steroids excreted were cortisol, 11beta,17alpha,20beta,21-tetrahydroxy-4-pregnen-3-one (20beta-dihydrocortisol), alpha- and beta-cortol and alpha- and beta-cortolone. The majority of the steroids were excreted unconjugated and a conspicuous feature of the pattern was the large amount of urinary free cortisol. Unlike man there was an insignificant excretion of 3alpha,17alpha,21-trihydroxy-5beta-pregnane-11,20-dione (tetrahydrocortisone) and 3alpha,11beta,17alpha,21-tetrahydroxy-5beta-pregnan-20-one (tetrahydrocortisol). A steroid not previously identified in urine from any species was one of the major glucuronide conjugates; it was characterized as having the structure 3beta,17alpha,20xi,21-tetrahydroxy-5beta-pregnan-11-one. Administration of dexamethosone resulted in complete suppression of steroid output, whilst the response to adrenocorticotrophic hormone was inconstant.

Adrenocorticotropic Hormone↗
PubMed1976

Phencyclidine sedation as a technique for handling rhesus monkeys: effects on LH, GH, and prolactin secretion.

Rhesus monkeys, sedated with phencyclidine hydrochloride (Sernylan), were quieted for prolonged periods of time, while maintaining somatic reflexes, muscle tone, and respiration. Brief daily periods of sedation did not interfere with the menstrual cycle. Prolonged sedation, however, interfered with the experimentally estrogen-induced LH surge, but not with the inhibitory action of estrogen on LH tonic secretion. Pulsatile release of LH, GH, and prolactin persisted even under prolonged sedation. The secretion of prolactin in response to the administration of TRH was increased in animals sedated with phencyclidine.

Animals↗
PubMed1976

The haematology of hypothyroidism.

In an unselected series of 202 patients with hypothyroidism anaemia was present on diagnosis in 39 of 172 women and 14 of 30 men. Microcytic anaemia was present in only nine patients in the entire series. The average of the mean corpuscular volume (MCV) of all the patients was 90 fl. Fifty-three of 118 patients who were studied in detail had normal serum concentrations of vitamin B12, folic acid and iron. The haemoglobin was low in 13 of these 53 patients and rose on treatment with thyroxine alone. The MCV exceeded 90 fl in 29 of these 53 patients and in three it was greater than 100 fl. The MCV invariably fell on treatment with thyroxine even if the initial value was within the normal range. Nine of this group of 53 patients had both anaemia and an increased MCV--the macrocytic anaemia of hypothyroidism. A minor degree of anisocytosis of the red blood cells, which was reduced by treatment with thyroxine, was also demonstrated. Acanthocytes were present in the blood films of 32 out of 172 patients but in only five did the abnormal cells comprise more than 0-5 per cent of the red cell population. The incidence of new cases of pernicious anaemia diagnosed concurrently with the hypothyroidism in the carefully studied group of 118 patients was 8-5 per cent. The MCV of hypothyroid patients with low levels of vitamin B12 was often no greater than in patients with uncomplicated hypothyroidism. The MCV is not therefore a useful discriminant in the diagnosis of pernicious anaemia in hypothyroidism. The serum iron concentration was less than 12 mumol/1 in 60 out of 118 patients. The total iron binding capacity of the serum was increased in only 21 of these 60 patients. In 42 hypothyroid patients the low serum iron concentration was not associated with low levels of either vitamin B12 or folate and of these patients 22 were anaemic. Despite the very low percentage saturation of the iron binding capacity in all of these patients with a low serum iron, a lack of iron did not seem to be the usual determinant of anaemia when it occurred.

Acanthocytes↗
PubMed1976

Aspects of the secondary antibody response to ox insulin in the Hartley guinea-pig; the use of chemically modified ox insulin to delineate the antigenic determinants of ox insulin.

The use of a quinea-pig model to study the immunogenicity of the insulin molecule is presented. The Hartley guinea-pig has been shown consistently to form antibody to ox insulin, when given in a water-in-oil emulsion containing pertussis vaccine as adjuvant. After log transformation of standardized antibody titres to iodo-ox insulin, a valid statistical comparison of the antibody response to different ox insulin preparations could be made. Antibody cross-reacting with ox insulin, but not iodo-ox insulin, was also detected. The quantity of one type of antibody was complementary to the other, an observation compatible with determinant competition having occurred during the immune response. From the results of cross-reactivity experiments using N-triacylated ox insulins and human insulin, it was shown that antibody cross-reacting with iodo-ox insulin had most probably been produced to a localized area of the molecule.

Animals↗
PubMed1976

Determinant competition during the immune response to N-acyl derivatives of ox insulin in the Hartley guinea-pig.

Subgroups of female Hartley guinea-pigs were immunized with N-carbamylated ox insulin, N-maleylated ox insulin, N-phthaloylated ox insulin, or with the crystalline ox insulin from which the N-acylated insulins had been prepared. The immunogens were administered in water-in-oil emulsions containing pertussis vaccine as adjuvant. Sera obtained 20 days after secondary immunization were assayed for their antibody titres to iodo-ox insulin and their insulin-binding capacities. The data were log transformed for statistical comparison. N-carbamylated ox insulin seemed to be as immunogenic as crystalline ox insulin and no specific carbamyl hapten antibody could be found. N-maleylated and N-phthaloylated ox insulins yelded significantly less antibody cross-reactingwith iodo-ox insulin, but produced a complementary quantity of specific maleyl and phthaloyl hapten antibody respectively. Thus it was shown that in the system used the immune response was partitioned between different determinants, ox insulin and its N-acylated derivatives being equipotent immunogens.

Acylation↗
PubMed1975

Studies on plasma corticosteroids in the rhesus monkey (Macaca mulatta).

The physiological regulation of the plasma corticosteroid concentration, measured by competitive protein-binding, was studied in female rhesus monkeys (M. mulatta) sedated with phencyclidine hydrochloride. Morning basal levels of plasma corticosteroids were found to be in the range 8-0-25-2 mug/100 ml, which is lower than that previously reported in this species. A circadian rhythm in plasma cortisol concentration was demonstrated. Prolonged sedation with phencyclidine was associated with a gradual increase in the plasma cortisol concentration. Synthetic alpha1-24 adrenocorticotrophic hormone given intravenously caused a rapid rise in plasma cortisol, the minimum effective dose was between 1 and 10 ng/kg body weight and the response was maximal after 1000 ng/kg. The administration of lysine-vasopressin and the induction of hypoglycaemia by insulin were both followed by an increase in the plasma corticosteroid concentration. Metyrapone caused a decline in plasma 11-hydroxycorticosteroids and a concomitant increase in total corticosteroids measured by competitive protein-binding. It is concluded that the hypothalamic-pituitary-adrenal system in the rhesus monkey functions in a manner which is qualitatively and quantitatively similar to that of man.

11-Hydroxycorticosteroids↗