scholarly journals Correlation between the Loss of Thyroglobulin Iodination and the Expression of Thyroid-Specific Proteins Involved in Iodine Metabolism in Thyroid Carcinomas

2003 ◽  
Vol 88 (10) ◽  
pp. 4977-4983 ◽  
Author(s):  
A.-C. Gérard ◽  
C. Daumerie ◽  
C. Mestdagh ◽  
S. Gohy ◽  
C. de Burbure ◽  
...  
Keyword(s):  
Polyclonal Antibodies ◽  
Apical Plasma Membrane ◽  
Hormone Synthesis ◽  
Iodide Transport ◽  
Tissue Sections ◽  
Weak Staining ◽  
Iodine Metabolism ◽  
Specific Proteins ◽  
Generating System

Abstract Progress in biotechnology has provided useful tools for tracing proteins involved in thyroid hormone synthesis in vivo. Mono- or polyclonal antibodies are now available to detect on histological sections the Na+/I− symporter (NIS) at the basolateral pole of the cell, the putative iodide channel (pendrin) at the apical plasma membrane, thyroperoxidase (TPO), and members of the NADPH-oxidase family, thyroid oxidase 1 and 2 (ThOXs), part of the H2O2-generating system. The aim of this study was to correlate thyroglobulin (Tg) iodination with the presence of these proteins. Tg, T4-containing Tg, NIS, pendrin, TPO, ThOXs, and TSH receptor (TSHr) were detected by immunohistochemistry on tissue sections of normal thyroids and various benign and malignant thyroid disorders. Tg was present in all cases. T4-containing Tg was found in the adenomas, except in Hurthle cell adenomas. It was never detected in carcinomas. NIS was reduced in all types of carcinomas, whereas it was detected in noncancerous tissues. Pendrin was not expressed in carcinomas, except in follicular carcinomas, where weak staining persisted. TPO expression was present in insular, follicular carcinomas and in follicular variants of papillary carcinomas, but in a reduced percentage of cells. It was below the level of detection in papillary carcinomas. The H2O2-generating system, ThOXs, was found in all carcinomas and was even increased in papillary carcinomas. Its staining was apical in normal thyroids, whereas it was cytoplasmic in carcinomas. The TSHr was expressed in all cases, but the intensity of the staining was decreased in insular carcinomas. In conclusion, our work shows that all types of carcinomas lose the capacity to synthesize T4-rich, iodinated Tg. In follicular carcinomas, this might be due to a defect in iodide transport at the basolateral pole of the cell. In papillary carcinomas, this defect seems to be coupled to an altered apical transport of iodide and probably TPO activity. The TSHr persists in virtually all cases.

EFFECTS OF AMIODARONE ON THYROID IODINE METABOLISM IN VITRO1)

1977 ◽  
Vol 85 (4) ◽  
pp. 781-790 ◽  
Author(s):  
Bernardo E. Gluzman ◽  
Aldo H. Coleoni ◽  
Héctor M. Targovnik ◽  
Hugo Niepomniszcze
Keyword(s):  
Thyroid Gland ◽  
Direct Action ◽  
The Other ◽  
Human Thyroid ◽  
Thyroid Peroxidase ◽  
Iodide Transport ◽  
Iodine Metabolism ◽  
Per Se ◽  
Rule Out

ABSTRACT Since alterations of thyroid function have been reported in patients treated with amiodarone, 2-butyl,3-(4-diethylaminoethoxy-3,5- diiodo, benzoyl) benzofuran, the effects of this drug on the active iodide transport, organic iodine formation, thyroid peroxidase and the enzymatic iodotyrosine deiodination, were studied. In pig thyroid slices the iodide transport was affected by amiodarone at concentrations of 10−4 m and 10−5 M, showing a decrease of T/M (tissue/medium) ratios of 20% and 23%, respectively. Lower concentrations produced no significant differences from the controls. Iodotyrosine synthesis was only, but poorly, affected by 10−4 m and 10−5 m amiodarone. Inhibition of the DIT formation was greater than that produced for MIT. Thyroid peroxidase activity, as measured by the tyrosine-iodinase assay, showed a 20% decrease at 10−3 m amiodarone. None of the other concentrations have affected the activity of the enzyme, except for 7% at a concentration of 10−4 m. The iodotyrosine deiodination was affected by amiodarone only at a concentration of 10−3 m and 10−4 m. The inhibitions were of 22.5% and 16.8%, respectively. We have concluded that, under the conditions of our study, amiodarone per se does not affect the intrathyroidal iodine metabolism in concentrations which are usually present in the sera of patients treated with this drug. However, it is not possible to rule out an in vivo direct action, if amiodarone is substantially concentrated in the human thyroid gland.

IODOAMINO ACID SYNTHESIS IN THYROID LOBES IN VITRO WITH EXCELLENT YIELD OF IODOTHYRONINES

1979 ◽  
Vol 92 (2) ◽  
pp. 286-294 ◽  
Author(s):  
Ken Okamura ◽  
Kenjiro Inoue ◽  
Toshiro Nakashima ◽  
Akiyo Shiroozu ◽  
Mototaka Yoshinari
Keyword(s):  
Potent Inhibitor ◽  
Acid Synthesis ◽  
Sprague Dawley ◽  
Hormone Synthesis ◽  
Sprague Dawley Rats ◽  
Unique Effect ◽  
Iodine Metabolism ◽  
Bovine Tsh

ABSTRACT Thyroid lobes of male Sprague-Dawley rats on an iodine-sufficient diet were incubated in our improved in vitro system with 0.01 μm 127I and 5 mU/ml of bovine TSH. Thyroidal 131I-uptake and the relative incorporation of iodine into iodothyronines increased with time. The average yield of each iodoamino acid after 8 h of incubation was: monoiodotyrosine 28.0 %, diiodotyrosine 46.5 %, triiodothyronine 1.9 % and thyroxine 13.9 %, which showed a striking resemblance to the values obtained in vivo. The yields of iodotyrosines and iodothyronines, the latter in particular, were strikingly high, and this system is considered to be useful in the study of thyroidal iodine metabolism. Effects of TSH, temperature and pH of the medium were examined and a unique effect of pH was observed on the iodoamino acid synthesis. As the pH was elevated from 6.8 to 7.9, 131I-uptake, MIT/DIT ratio, T4/DIT ratio and T3/T4 ratio increased. The effect of slightly alkaline pH was considered to be similar to that observed in iodine-deficiency. It was found that the rubber stoppers which are commonly used in shortterm incubation contain a kind of potent inhibitor of thyroid hormone synthesis. The pattern of inhibition was similar to that of thionamide compounds.

Physiological, morphological, and immunochemical parameters used for the characterization of clinical and environmental isolates ofAcanthamoeba

Parasitology ◽  
2012 ◽  
Vol 140 (3) ◽  
pp. 396-405 ◽  
Author(s):  
A. BECKER-FINCO ◽  
A. O. COSTA ◽  
S. K. SILVA ◽  
J. S. RAMADA ◽  
C. FURST ◽  
...  
Keyword(s):  
Comparative Evaluation ◽  
Polyclonal Antibodies ◽  
Protein Profiles ◽  
Environmental Isolates ◽  
Pathogenic Potential ◽  
Cytopathic Effects ◽  
Specific Proteins

SUMMARYThe factors that characterizeAcanthamoebastrains as harmless or potentially pathogenic have not been elucidated. Analysing thein vitroandin vivoparameters ofAcanthamoebasamples, including heat tolerance at temperatures close to that of the human body, cytopathic effects, and their ability to cause infections in animals, has been proposed to identify their pathogenic potential. Another promising criterion for differentiating strains is the analysis of their biochemical and immunochemical properties. In this study, a comparative evaluation between clinical and environmentalAcanthamoebaisolates was performed on the basis of physiological, morphological, and immunochemical criteria. Crude antigens were used to characterize the protein profiles by electrophoresis and immunize mice to produce polyclonal and monoclonal antibodies. The antibodies were characterized using ELISA, Western blotting, and immunofluorescence techniques. The results obtained with polyclonal antibodies suggest the presence of specific proteins for each studied isolate and co-reactive immunochemical profiles among conserved components. Ten monoclonal antibody clones were obtained; mAb3 recognized 3 out of 4 samples studied. The results of this study may help standardize criteria for identifying and characterizingAcanthamoebastrains. Taken together, our results support the view that a set of features may help differentiateAcanthamoebaspecies and isolates.

scholarly journals Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Poushali Chakraborty ◽  
Sapna Bajeli ◽  
Deepak Kaushal ◽  
Bishan Dass Radotra ◽  
Ashwani Kumar
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune System ◽  
Biofilm Formation ◽  
Antimycobacterial Activity ◽  
Drug Tolerance ◽  
Host Immune System ◽  
Tissue Sections ◽  
Slow Growing

AbstractTuberculosis is a chronic disease that displays several features commonly associated with biofilm-associated infections: immune system evasion, antibiotic treatment failures, and recurrence of infection. However, although Mycobacterium tuberculosis (Mtb) can form cellulose-containing biofilms in vitro, it remains unclear whether biofilms are formed during infection in vivo. Here, we demonstrate the formation of Mtb biofilms in animal models of infection and in patients, and that biofilm formation can contribute to drug tolerance. First, we show that cellulose is also a structural component of the extracellular matrix of in vitro biofilms of fast and slow-growing nontuberculous mycobacteria. Then, we use cellulose as a biomarker to detect Mtb biofilms in the lungs of experimentally infected mice and non-human primates, as well as in lung tissue sections obtained from patients with tuberculosis. Mtb strains defective in biofilm formation are attenuated for survival in mice, suggesting that biofilms protect bacilli from the host immune system. Furthermore, the administration of nebulized cellulase enhances the antimycobacterial activity of isoniazid and rifampicin in infected mice, supporting a role for biofilms in phenotypic drug tolerance. Our findings thus indicate that Mtb biofilms are relevant to human tuberculosis.

scholarly journals Identification of Two Cross-Neutralizing Linear Epitopes within the L1 Major Capsid Protein of Human Papillomaviruses

2002 ◽  
Vol 76 (13) ◽  
pp. 6480-6486 ◽  
Author(s):  
Alba-Lucia Combita ◽  
Antoine Touzé ◽  
Latifa Bousarghin ◽  
Neil D. Christensen ◽  
Pierre Coursaget
Keyword(s):  
Neutralizing Antibodies ◽  
Polyclonal Antibodies ◽  
Human Papillomaviruses ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
Linear Epitopes ◽  
Cross Neutralization ◽  
Definition Of ◽  
L1 Protein

ABSTRACT The neutralizing activities of polyclonal antibodies and monoclonal antibodies (MAbs) obtained by immunization of mice with L1 virus-like particles (VLPs) were investigated by using pseudovirion infectivity assays for human papillomavirus type 16 (HPV-16), HPV-31, HPV-33, HPV-45, HPV-58, and HPV-59 to obtain a better definition of cross-neutralization between high-risk HPVs. In this study, we confirmed and extended previous studies indicating that most genital HPV genotypes represent separate serotypes, and the results suggest that the classification of serotypes is similar to that of genotypes. In addition, three cross-neutralizing MAbs were identified (HPV-16.J4, HPV-16.I23, and HPV-33.E12). MAb HPV-16.J4 recognized a conserved linear epitope located within the FG loop of the L1 protein, and HPV-16.I23 recognized another located within the DE loop. The results suggested that reactivity of MAb HPV-16.I23 to L1 protein is lost when leucine 152 of the HPV-16 L1 protein is replaced by phenylalanine. This confirmed the existence of linear epitopes within the L1 protein that induce neutralizing antibodies, and this is the first evidence that such linear epitopes induce cross-neutralization. However, the cross-neutralization induced by L1 VLPs represents less than 1% of the neutralizing activity induced by the dominant conformational epitopes, and it is questionable whether this is sufficient to offer cross-protection in vivo.

scholarly journals A New Diagnostic System for Detection of ‘Candidatus Liberibacter asiaticus’ Infection in Citrus

Plant Disease ◽  
2013 ◽  
Vol 97 (10) ◽  
pp. 1295-1300 ◽  
Author(s):  
Lianming Lu ◽  
Baoping Cheng ◽  
Jinai Yao ◽  
Aitian Peng ◽  
Danchao Du ◽  
...  
Keyword(s):  
Affinity Chromatography ◽  
Polyclonal Antibodies ◽  
Diagnostic System ◽  
Enzyme Linked Immunosorbent Assay ◽  
Candidatus Liberibacter Asiaticus ◽  
Negative Results ◽  
Candidatus Liberibacter ◽  
Liberibacter Asiaticus ◽  
Polymerase Chain

In this study, two polyclonal antibodies were produced against the Omp protein of ‘Candidatus Liberibacter asiaticus’. First, omp genes were sequenced to exhibit 99.9% identity among 137 isolates collected from different geographical origins. Then, two peptides containing the hydrophobic polypeptide-transport-associated (POTRA) domain and β-barrel domain, respectively, were identified on Omp protein. After that, these two peptides were overexpressed in Escherichia coli and purified by affinity chromatography to immunize the white rabbits. Finally, the antiserum was purified by affinity chromatography. The two Omp antibodies gave positive results (0.454 to 0.633, 1:1,600 dilution) in enzyme-linked immunosorbent assay against ‘Ca. L. asiaticus’-infected samples collected from different geographical origins but revealed negative results against other pathogen-infected, nutrient-deficient and healthy samples. The antibody against the POTRA domain of Omp protein could detect ‘Ca. L. asiaticus’ in 45.7% of the symptomatic samples compared with a 56.2% detection rate with a polymerase chain reaction assay. These new antibodies will provide a very useful supplement to the current approaches to ‘Ca. L. asiaticus’ detection and also provide powerful research tools for tracking distribution of this pathogen in vivo.

scholarly journals News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 252
Author(s):  
Jacopo Meldolesi
Keyword(s):  
Neurodegenerative Diseases ◽  
Imaging Techniques ◽  
Imaging Biomarkers ◽  
Positron Emission ◽  
Specific Proteins ◽  
Great Relevance ◽  
The Brain ◽  
Positive Point

Biomarkers are molecules that are variable in their origin, nature, and mechanism of action; they are of great relevance in biology and also in medicine because of their specific connection with a single or several diseases. Biomarkers are of two types, which in some cases are operative with each other. Fluid biomarkers, started around 2000, are generated in fluid from specific proteins/peptides and miRNAs accumulated within two extracellular fluids, either the central spinal fluid or blood plasma. The switch of these proteins/peptides and miRNAs, from free to segregated within extracellular vesicles, has induced certain advantages including higher levels within fluids and lower operative expenses. Imaging biomarkers, started around 2004, are identified in vivo upon their binding by radiolabeled molecules subsequently revealed in the brain by positron emission tomography and/or other imaging techniques. A positive point for the latter approach is the quantitation of results, but expenses are much higher. At present, both types of biomarker are being extensively employed to study Alzheimer’s and other neurodegenerative diseases, investigated from the presymptomatic to mature stages. In conclusion, biomarkers have revolutionized scientific and medical research and practice. Diagnosis, which is often inadequate when based on medical criteria only, has been recently improved by the multiplicity and specificity of biomarkers. Analogous results have been obtained for prognosis. In contrast, improvement of therapy has been limited or fully absent, especially for Alzheimer’s in which progress has been inadequate. An urgent need at hand is therefore the progress of a new drug trial design together with patient management in clinical practice.

THE INFLUENCE OF THE PLASMA INORGANIC IODINE CONCENTRATION ON THYROID FUNCTION IN DEHALOGENASE DEFICIENCY

1967 ◽  
Vol 55 (2) ◽  
pp. 361-368 ◽  
Author(s):  
R. McG. Harden ◽  
W. D. Alexander ◽  
S. Papadopoulos ◽  
M. T. Harrison ◽  
S. Macfarlane
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Function ◽  
Iodine Concentration ◽  
Rapid Rise ◽  
Normal Range ◽  
Hormone Synthesis ◽  
Thyroid Hormone Synthesis ◽  
Iodine Metabolism ◽  
Inorganic Iodine ◽  
Circulating Levels

ABSTRACT Iodine metabolism and thyroid function were studied in a patient with hypothyroidism and goitre due to dehalogenase deficiency. Initially the plasma inorganic iodine (PII) level was within the normal range but circulating levels of hormone were low and the thyroid clearance and absolute uptake of iodine (AIU) by the thyroid were high. Administration of iodide supplements resulted in a rapid rise in the plasma thyroxine concentration and restoration of the euthyroid state. Thyroid hormone synthesis appeared to proceed normally when the PII exceeded 1.0 μg/100 ml. This was achieved by increasing the intake of iodide by 612 μg per day. At PII levels around 10 μg/100 ml there was evidence of increased levels of circulating thyroid hormone.

scholarly journals The importance of sodium/iodide symporter (NIS) for thyroid cancer management

2007 ◽  
Vol 51 (5) ◽  
pp. 672-682 ◽  
Author(s):  
Denise P. Carvalho ◽  
Andrea C.F. Ferreira
Keyword(s):  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Therapeutic Tool ◽  
Iodide Transport ◽  
Cancer Management ◽  
Thyroid Hormone Biosynthesis ◽  
Nis Gene ◽  
Hormone Biosynthesis ◽  
Tumoral Cells

The thyroid gland has the ability to uptake and concentrate iodide, which is a fundamental step in thyroid hormone biosynthesis. Radioiodine has been used as a diagnostic and therapeutic tool for several years. However, the studies related to the mechanisms of iodide transport were only possible after the cloning of the gene that encodes the sodium/iodide symporter (NIS). The studies about the regulation of NIS expression and the possibility of gene therapy with the aim of transferring NIS gene to cells that normally do not express the symporter have also become possible. In the majority of hypofunctioning thyroid nodules, both benign and malignant, NIS gene expression is maintained, but NIS protein is retained in the intracellular compartment. The expression of NIS in non-thyroid tumoral cells in vivo has been possible through the transfer of NIS gene under the control of tissue-specific promoters. Apart from its therapeutic use, NIS has also been used for the localization of metastases by scintigraphy or PET-scan with 124I. In conclusion, NIS gene cloning led to an important development in the field of thyroid pathophysiology, and has also been fundamental to extend the use of radioiodine for the management of non-thyroid tumors.

scholarly journals The Ability of Zika virus Intravenous Immunoglobulin to Protect From or Enhance Zika Virus Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Amelia K. Pinto ◽  
Mariah Hassert ◽  
Xiaobing Han ◽  
Douglas Barker ◽  
Trevor Carnelley ◽  
...  
Keyword(s):  
Virus Infection ◽  
Polyclonal Antibody ◽  
Zika Virus ◽  
Virus Disease ◽  
Polyclonal Antibodies ◽  
Antibody Therapeutics ◽  
The World ◽  
Flavivirus Infection

The closely related flaviviruses, dengue and Zika, cause significant human disease throughout the world. While cross-reactive antibodies have been demonstrated to have the capacity to potentiate disease or mediate protection during flavivirus infection, the mechanisms responsible for this dichotomy are still poorly understood. To understand how the human polyclonal antibody response can protect against, and potentiate the disease in the context of dengue and Zika virus infection we used intravenous hyperimmunoglobulin (IVIG) preparations in a mouse model of the disease. Three IVIGs (ZIKV-IG, Control-Ig and Gamunex®) were evaluated for their ability to neutralize and/or enhance Zika, dengue 2 and 3 viruses in vitro. The balance between virus neutralization and enhancement provided by the in vitro neutralization data was used to predict the IVIG concentrations which could protect or enhance Zika, and dengue 2 disease in vivo. Using this approach, we were able to define the unique in vivo dynamics of complex polyclonal antibodies, allowing for both enhancement and protection from flavivirus infection. Our results provide a novel understanding of how polyclonal antibodies interact with viruses with implications for the use of polyclonal antibody therapeutics and the development and evaluation of the next generation flavivirus vaccines.

Sign in / Sign up

Export Citation Format

Share Document