A5055004417- Thyroid Disorders and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Diabetes and associated disorders
- Adrenal Hormones and Disorders
- Glycosylation and Glycoproteins Research
- Neuropeptides and Animal Physiology
- Hormonal Regulation and Hypertension
- Growth Hormone and Insulin-like Growth Factors
- Thyroid Cancer Diagnosis and Treatment
- Pancreatic function and diabetes
- T-cell and B-cell Immunology
- Diabetes Management and Research
- Receptor Mechanisms and Signaling
- Erythrocyte Function and Pathophysiology
- Ion channel regulation and function
- Blood groups and transfusion
- Hormonal and reproductive studies
- Hypothalamic control of reproductive hormones
- Urticaria and Related Conditions
- Digestive system and related health
- Toxin Mechanisms and Immunotoxins
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Radiopharmaceutical Chemistry and Applications
- Ophthalmology and Eye Disorders
Cardiff University
2012-2021
RF Laboratories (United States)
2011-2019
Integrated Radiological Services (United Kingdom)
2013
University of Wales
1995-2004
Rotordynamics-Seal Research (United States)
2004
University of Padua
1996
University College London
1993
Newcastle University
1974-1991
St. Mary's Hospital
1991
Scripps Research Institute
1991
SUMMARY An improved receptor assay for TSH antibodies is described in which detergent‐solubilized receptors and 125 I‐labelled are used. Normal human serum immunoglobulin concentrates from normal showed little effect on the interaction between labelled whereas some Graves' sera caused marked inhibition of binding. Precipitation with polyethylene glycol was most convenient way preparing using this technique could be completed a few hours. The coefficient inter variation at 51% binding 3.7%...
Microsomal antibodies and directed toward the receptor for thyroid-stimulating hormone (TSH) decreased in parallel while patients with Graves' disease were taking carbimazole, whereas no significant changes observed during treatment placebo or propranolol. The autoantibody levels carbimazole independent of serum thyroxine could have been due to a direct effect drug on synthesis. Evidence this suggestion was provided when low doses methimazole (the active metabolite carbimazole) found inhibit...
Autoantibodies to steroidogenic enzymes, steroid 17 alpha-hydroxylase (17 alpha-OH), cytochrome P450 side-chain cleavage enzyme (P450scc), and 21-hydroxylase (21-OH), were measured using specific sensitive immunoprecipitation assays (IPAs) in patients with various forms of autoimmune adrenal disease. alpha-OH detected 6 11 (55%) polyglandular syndrome (APS) type I, 8 24 (33%) APS II, 56 (20%) cortex antibody (ACA; by immunofluorescence)-positive without Addison's disease, only 3 64 (5%)...
To analyze interactions between the thyroid-stimulating hormone receptor (TSHR) and a human monoclonal autoantibody (M22) at molecular level.A complex of part TSHR extracellular domain (amino acids 1-260; TSHR260) bound to M22 Fab was prepared purified. Crystals suitable for X-ray diffraction analysis were obtained structure solved 2.55 A resolution.TSHR260 comprises curved helical tube clasps its concave surface 90 degrees length axis. The interface buried in is large (2,500 A(2)) an...
Abstract These highly sensitive assays are based on the interaction between thyroid autoantibodies and 125I-labeled autoantigens. Serum samples incubated with labeled peroxidase (TPO) or thyroglobulin (Tg) to allow formation of antibody-labeled antigen complexes. The complexes then precipitated by addition solid-phase Protein A. In presence high concentrations TPO antibody Tg antibody, more than 50% respective was precipitated, whereas only 1-2% in absence autoantibody. Interassay CVs were...
SUMMARY A receptor assay for TSH antibodies is described in which unextracted serum, detergent solubilised receptors and 125 I‐labelled are used. The was rapid reproducible with coefficients of inter‐assay variation 12·3%, 2·1 2·6% at mean inhibition binding values 11, 53, 79 respectively. Assay sensitivity could be increased by reducing the volume used but some increase scatter obtained individual normal sera also observed. Comparison human porcine preparations indicated that tissue gave...
In Graves' disease (GD), autoantibodies to the thyroid stimulating hormone receptor (TSHR) cause hyperthyroidism. The condition is often associated with eye signs including proptosis, oedema, and diplopia (collectively termed orbitopathy [GO]). safety profile of K1-70TM (a human monoclonal TSHR specific autoantibody, which blocks ligand binding stimulation receptor) in patients GD was evaluated a phase I clinical trial.Eighteen stable on antithyroid drug medication received single...
Abstract Adrenal cortex autoantibodies (ACA) were measured by immunofluorescence in 808 children with organ-specific autoimmune diseases without adrenal insufficiency. ACA found 14 (1.7%), mostly hypoparathyroidism (48%). Ten ACA-positive and 12 ACA-negative followed up for a maximum of 10 yr evaluation adrenocortical function (ACTH test) autoantibody status. In all patients steroid-producing cell assessed to steroid 21-hydroxylase, 17α-hydroxylase, cytochrome P450 side-chain cleavage enzyme...
In order to determine whether the geographical distribution of autoimmune thyroid disease in Britain is influenced by pattern iodine intake, prevalence subclinical (detectable antithyroid antibodies biochemically euthyroid individuals) has been measured female blood donors from seven towns England and Wales previously characterised terms past present intake. Thyroglobulin antibody peroxidase were highly sensitive assays which are based on direct interaction between radiolabelled antigen....
Context: Patients with adrenal cortex autoantibodies (ACA) without overt autoimmune Addison’s disease (AAD) are at risk of failure. Design: To assess the contribution different clinical, immunological, genetic, and functional factors in progression to AAD, we followed up 100 ACA-positive 63 ACA-negative patients AAD for a maximum 21 yr (mean 6.0 yr, median 4.8). ACA were measured by immunofluorescence 21-OH (Abs) RIA. Adrenal function was assessed measuring basal levels cortisol,...
Patients who appear to have both stimulating and blocking TSHR autoantibodies in their sera been described, but the two activities not separated analysed. We now describe isolation detailed characterization of a type monoclonal autoantibody from single sample peripheral blood lymphocytes.Two heterohybridoma cell lines secreting were isolated using standard techniques lymphocytes patient with hypothyroidism high levels (160 units/l by inhibition TSH binding). The ability new antibodies (MAbs;...
A complex of the TSH receptor extracellular domain (amino acids 22–260; TSHR260) bound to a blocking-type human monoclonal autoantibody (K1-70) was purified, crystallised and structure solved at 1.9 Å resolution. K1-70 Fab binds concave surface TSHR leucine-rich (LRD) forming large interface (2565 Å2) with an extensive network ionic, polar hydrophobic interactions. Mutation or residues showing strong interactions in influenced activity K1-70, indicating that binding detail observed reflects...
The design of the study was to investigate prevalence following: 1) premature ovarian failure (POF) in patients with autoimmune Addison's disease (AD); 2) steroid-producing cell antibodies (StCA) and steroidogenic enzymes (17α-hydroxylase autoantibodies P450 side-chain cleavage enzyme autoantibodies) or without POF; 3) value these predict POF.The included 258 women: 163 polyendocrine syndrome type 2 (APS-2), 49 APS-1, 18 APS-4, 28 isolated AD.StCA were measured by an immunofluorescence...
Addison's disease (AD) is a rare endocrine condition.We aimed to evaluate clinical, immunologic, adrenal imaging, and genetic features in 633 Italian patients with AD followed up since 1967.Adrenal cortex autoantibodies, presence of other autoimmune nonautoimmune diseases, nonadrenal profile for HLA-DRB1 AIRE were analyzed.A total 492 (77.7%) found be affected by (A-AD), 57 (9%) tuberculous AD, 29 (4.6%) genetic-associated 10 (1.6%) cancer, six (0.94%) post-surgical four (0.6%) vascular...
Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized three major manifestations: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism (CH) Addison's disease (AD).Autoimmune conditions associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females 55 males; F/M 1.9/1) at the onset during follow-up of 23.7 ± 15.1 years. AIRE determined.The prevalence APS-1 was...
Thyrotropin (TSH) receptor monoclonal antibodies (TSHR mAbs) were obtained from cDNA-immunized NMRI mice. Three mAb immunoglobulin Gs (IgGs) (TSmAbs 1-3) that had distinct V(H )and V(L) region sequences stimulated cyclic adenosine monophosphate (cAMP) production in isolated porcine thyroid cells greater than 10x basal and as little 20 ng/mL (0.13 nmol/L) of TSmAb 1 IgG caused a 2x stimulation. 2 Fab fragments also effective stimulators thyroid-stimulating activities the IgGs Fabs confirmed...
An adrenal-specific protein reacting with autoantibodies in the sera of patients adult onset Addison's disease has been purified from human adrenal glands. The protein, mol.wt. 55K, biochemical characteristics steroid 21-hydroxylase and reacts on Western blots rabbit antibodies to recombinant 21-hydroxylase. Absorption native 55K prevented subsequent reaction blot analysis. In addition, reacted expressed yeast. These data indicate that specific enzyme is a major autoantigen involved...
A new procedure for measuring patient serum thyrotropin receptor (TSHR) autoantibodies is described in which the inhibit binding of a human monoclonal thyroid stimulating antibody M22 (labeled with biotin) to TSHR-coated enzyme-linked immunosorbent assay (ELISA) plate wells. In assay, M22-biotin detected by addition streptavidin peroxidase. The based was more sensitive than similar ELISA on inhibition TSH-biotin TSHR coated wells 1 U/L NIBSC 90/672 giving approximately 35% M22-based system...