摘要:

SUMMARYEighteen patients with postmenopausal gonadotrophin levels and secondary amenorrhoea before the age of 35 years (premature ovarian failure, POF) were examined for the presence of cellular and humoral immune defects. Six patients had an abnormally low natural killer (NK) cell activity. The levels of circulating immune complexes were increased in six patients. Tissue antibodies were detected in six patients and two of these possessed ovarian antibodies. Leukocyte migration inhibition in the presence of ovarian antigen was slightly enhanced in three patients. Altogether 12 patients (66%) with POF had some immunological defect or defects suggesting that immune mechanisms are often involved in the aetiology of POF.

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03589.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYWe have investigated the effect of methimazole (MMI) on cell‐mediated immunity and ascertained the mechanisms of immunosuppression produced by the drug. Methimazole (≥ 10−5m) produced a dose‐dependent inhibition in ‘active’ (early) rosette formation with sheep red cells and in phytohaemagglutinin (PHA)‐induced lymphocyte transformation. A concentration of 10−4M MMI inhibited the immediate rise in intracellular cAMP triggered by PHA and the subsequent time dependent decrement over 24 h. The drug (10−3M) also exerted a significant inhibitory effect on antibody‐dependent cell‐mediated cytotoxicity (ADCC) over six‐fold difference in target/effector cell ratios. At a concentration of 10−5M, MMI inhibited zymosan‐induced respiratory burst (determined by change in the chemiluminescence of oxidized luminol) in polymorphonuclear and mononuclear cell preparations. Ninety‐five per cent of the chemiluminescence in the latter preparation was due to monocytes. At concentrations between 10−7and 10−6M, MMI significantly inhibited (in cell‐free systems) horseradish peroxidase‐dependent generation of chemiluminescence as well as the oxidation of luminol by hydrogen peroxide. Methimazole exerts its inhibitory effects on measures of cell‐mediated immunity by at least two mechanisms: inhibition of peroxidase and scavenging free oxygen radicals. Insensitivity of the test systems or poor access of MMI to leucocytes may account for the need for ≥ 10−5m MMI to i

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03590.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYWe have recently reported an increase in HLA‐DR1 in 52 patients with thyroid epithelial cancer from Eastern Hungary (Juhaszet al., 1986). We have now investigated the association of IgG heavy chain markers (Gm) in 50 patients with this disease and explored possible interaction between Gm and HLA in modifying the risk for thyroid cancer. No Gm phenotype showed significant increases in the patients compared to 168 local controls. When both Gm and HLA, however, were considered, a marked heterogeneity in risk was noted. The odds ratio for DR1+fb+homozygotes was 37.5, for DR1+fb−individuals 60 and for DR1−fb+individuals 2.6 (DR1−fb−= 1.0). Thus Gm and HLA interact to enhance greatly the risk of thyro

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03591.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThyroid autoantibodies are common in Type I diabetics and their first degree relatives and may be part of the autoimmune diathesis present within such families. We have measured the prevalence of microsomal (M‐Ab) and thyroglobulin (Tg‐Ab) autoantibodies in 84 HLA‐typed families having a Type 1 diabetic child, using enzyme‐linked immunosorbent assay techniques. Thyroid autoantibodies were detectable in 201/407 (49%) individuals in these families. Both autoantibodies were significantly more frequent in the subsets of parents, diabetic children and their non‐diabetic siblings than in groups of control adults and children. The prevalence of these autoantibodies in the diabetic families was increased in both sexes with a female:male ratio of 1.4:1. Antigen DR5 was significantly associated with M‐Ab production but only for male subjects (P= 0.005 after correction for the number of DR antigens tested). No significant associations were encountered for Tg‐Ab. Within‐family analyses indicated that thyroid autoantibodies occurred with increased prevalence in HLA‐identical or haplo‐identical siblings of autoantibody‐positive index cases in comparison to control children. We conclude (1) the DR association with thyroid autoantibody production in this diabetes‐selected population was thyroiditis‐related and not diabetes‐related, and (2) the DR5 association was restricted to males and the production of M‐Ab. These data are consistent with the hypothesis that multiple genetic and non‐genetic factors played a role in the high prevalence of thyroid au

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03592.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYWe have treated five GH‐deficient prepubertal children (4 M, 1 F) with GH releasing hormone1–40(GHRH1–40) in two dosage regimens over 9 months. Profiles of serum GH concentrations were obtained over 24 hours before treatment and nocturnal profiles were obtained serially throughout the study. GHRH was administered subcutaneously at night for four pulses using 1 μg/kg/pulse in the first 3 months and 2 μg/kg/pulse for a further 6 months. All subjects demonstrated pituitary responsiveness to i.v. GHRH before treatment and at 3 and 6 months. GH secretion was induced in a pulsatile fashion in response to subcutaneous GHRH in three children from the first night of treatment. A self priming effect to successive GHRH pulses was evident and the response augmented with time and with the higher dose regimen. The growth velocity of these three children increased from a mean of 3.7 cm/year (range 3.7–3.8) before treatment to 5.5 cm/year (range 4.1–7.2) over the first 3 months and to 7.2 cm/ year (range 4.8–9.2) over the following 6 months. In one subject entrainment of GH secretion to GHRH did not occur until the higher dose regimen and this was associated with a modest increase in growth velocity. One subject did not respond to treatment. Pulsatile administration of GHRH1–40is effective in inducing GH secretion and promoting growth acceleration in some children with idiopathic GH deficiency. The optimal dose and mode of administration of GHRH have yet to

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03593.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYWe investigated the influence of TSH receptor antibody (TRA), as detected by inhibition of125I‐bTSH binding to detergent solubilized porcine TSH receptors, on in‐vitro thyroglobulin (hTg) production using normal thyroid cells in monolayer. Secretion of hTg into the culture medium was analysed by a noncompetitive enzyme immunosorbent (ELISA) technique utilizing two murine monoclonal antibodies. Basal hTg release (mean ± SD 124 ± 27 ng/105cells/6 d,n= 5) was stimulated by bTSH (10, 102, 103μU/ml) in a dose related manner (mean ± SD 191 ±24, 587 ±80, 695 ±66 ng/105cells/6 d, respectively). IgG (2 mg/ml) from seven patients with hyperthyroid Graves' disease, and known titres of TRA, similarly enhanced production of hTg, in a dose and time‐dependent manner, when compared to control IgG. The degree of induction varied from a 140–230% increase in total hTg release over a 6‐day incubation period. There was a direct correlation between the degree of125I‐bTSH binding inhibitory activity and the hTg response (r= 0.9,P<001). These data demonstrate that TSH receptor antibodies enhance hTg release from human thyroid cell monolayers and allow an assessment to be made of antibody‐activated post

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03594.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThe human population which lives and works in polar environments has been increasing steadily over the last 15 years. Very little is known about how these residents adjust to their environment. Cold adaptation in man is a poorly understood phenomenon. Euthermic mammals maintain body temperature during cold exposure via non‐shivering thermogenesis, a process which is hormonally mediated. We studied prospectively the response of the hypothalamic‐pituitary‐thyroid axis in 17 euthyroid men before, during and after assignment to duty in the Antarctic. Serum total and free T4 levels fell slightly but not significantly after very prolonged Antarctic residence. Serum total and free T3 decreased significantly from basal levels of 170 ± 3 ng/dl and 388 ± 19 pg/ dl to 155 ±5 ng/dl and 319±14 pg/dl respectively after Antarctic duty. Serum T3 levels increased after 42 weeks of polar living, the end of the observation period, but the change did not attain statistical significance. The integrated TSH response to TRH administration increased by 50% to 734 ± 58 μIU.min/ml over warm climate basal response levels of 456 ± 33 μIU.min/ml by the end of the study. The daily circadian rhythm of serum Cortisol was maintained throughout the study period. The alterations in thyroid hormones which we describe, are apparently related to the chronic cold exposure which our subjects experienced in this pola

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03595.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYA radioimmunoassay (RIA) specific for the synthetic 53–70 peptide region of human insulin‐like growth factor I (IGF‐I) was used to determine IGF‐I in the serum of 191 healthy newborns, children and adolescents and in 26 adults. The results compare favourably with reported values obtained using RIA systems for the native IGF‐I molecule. Intra‐ and inter‐assay CV were 3.3 and 7.2% respectively. In childhood, mean ± SD IGF‐I levels rise from 60 ± 3.5 nmol/l in newborns to 16.5±4.0 nmol/l at 8–11 years in both sexes. At the onset of puberty, IGF‐I levels in females (24.9 ± 6.6 nmol/l) are significantly (P>0.005) higher than in males (17.2 ± 4.2 nmol/l). With further pubertal development IGF‐I levels continue to rise, reaching peak values at pubertal stage P4(40.6 ± 4.5 nmol/l in males, 42.8 ± 5.1 nmol/l in females) and decline thereafter to lower values during adulthood: 16.5 ± 5.8 nmol/l (males) and 24.2 ± 7.0 nmol/l (females) (P>0.001). In pubertal males, IGF‐I correlates significantly with height (r= 0.66,P0.001) and growth velocity (r= 0.64,P= 0.025) as well as with testosterone levels (r= 0.69,P<0.001). In pubertal females a significant correlation is found between IGF‐I and height (r= 0.55,P<0.020). The ready availability of a simple, precise and reproducible IGF‐I RIA, should contribute much to evaluating the importance of IGF‐I measurements in normal growth and in the diagnosis a

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03596.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThe circulating levels of ACTH and α‐melanocyte stimulating hormone (α‐MSH) were measured in 9 patients with Nelson's syndrome after the administration of saline, ovine corticotrophin releasing factor (oCRF), bromocriptine or TRH. The concentrations of ACTH were grossly elevated and α‐MSH levels ranged from undetectable to higher than the normal range. In seven of eight subjects there was a rapid corticotrophic response, but no change in the α‐MSH level, following oCRF. This response was delayed in one subject. Following oCRF injection, the plasma oCRF profile was variable but circulating oCRF was detectable even at the end of the experiment in all cases. There was no significant change in circulating ACTH or α‐MSH following either bromocriptine or TRH. Cultured tumour cells from one case of Cushing's disease showed a corticotrophic response but no change in α‐MSH to oCRF and the response was enhanced by vasopressin. Bromocriptine added to the same tumour depressed ACTH secretion without affecting the output of α‐MSH. The present data suggest that the tumours in these subjects are responsive to oCRF and arise from corticotrophs rath

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03597.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYIn normal man the sympathetic nervous system could exert an inhibitory influence on aldosterone responsiveness to angiotensin II. The possible role of alpha‐1 adrenoceptors in the modulation of aldosterone response was assessed by studying the changes of plasma aldosterone during infusion of angiotensin II at the doses of 1, 2, 5 and 10 ng/kg.min or after1–24corticotrophin injection, 0.25 mg, in 9 normal subjects before and after treatment with the selective alpha‐1 adrenoceptor antagonist, prazosin. Prazosin, given during 3 weeks, did not modify supine arterial pressure, heart rate and the plasma levels of angiotensin II, renin, aldosterone or adrenaline but caused a significant (P<005) increase of plasma noradrenaline. The correlation relating plasma aldosterone to plasma angiotensin II levels before and during angiotensin II infusion and the response of plasma aldosterone to corticotrophin was not modified by prazosin. These findings suggest that in normal man there is no inhibitory influence of the noradrenergic system on aldosterone responsiveness to angiotensin II mediated by an alpha‐1 dependent me

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03598.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY