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3 results on '"Akulevich N"'

1. Optimal Pubertal Induction in Girls with Turner Syndrome Using Either Oral or Transdermal Estradiol: A Proposed Modern Strategy

Author

Donaldson, M., Kristrom, B., Ankarberg-Lindgren, C., Verlinde, S., Van Alfen-Van Der Velden, J., Gawlik, A., Van Gelder, M. M. H. J., Sas, T., Agota, M., Akulevich, N., Albertsson-Wikland, K., Bober, E., Buyukgebiz, A., Carel, J. -C., Dacou-Voutetakis, C., De Muinck Keizer-Schrama, S., Gault, E. J., Ghizzoni, L., Kanaka-Gantenbein, C., Kurtev, A., Malecka-Tendera, E., Mazzanti, L., Norjavaara, E., Popovic, J., Ranke, M., Sallai, A., Stagi, S., Wasniewska, M., Zenaty, D., Zuckerman-Levin, N., and Pediatrics

Subjects
Pediatrics, medicine.medical_specialty, Adolescent, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Administration, Oral, Turner Syndrome, 030209 endocrinology & metabolism, Administration, Cutaneous, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, 0302 clinical medicine, Endocrinology, 17β-estradiol, Oral induction, Puberty, Transdermal induction, Turner syndrome, Humans, Medicine, Sexual Maturation, Child, Prospective cohort study, Transdermal, 030219 obstetrics & reproductive medicine, Estradiol, medicine.diagnostic_test, business.industry, Vascular disease, Estrogen Replacement Therapy, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], medicine.disease, Regimen, Blood pressure, Estrogen, Pediatrics, Perinatology and Child Health, Female, business, Lipid profile
Abstract

Background: Most girls with Turner syndrome (TS) require pubertal induction with estrogen, followed by long term replacement. However, no adequately powered prospective studies comparing transdermal with oral 17β-estradiol administration exist. This reflects the difficulty of securing funding to study a rare condition with relatively low morbidity/mortality when competing against conditions such as cancer and vascular disease. Protocol Consensus: The TS Working Group of the European Society for Paediatric Endocrinology (ESPE) has agreed to both a 3-year oral and a 3-year transdermal regimen for pubertal induction. Prerequisites include suitable 17β-estradiol tablets and matrix patches to allow the delivery of incremental doses based on body weight. Study Proposal: An international prospective cohort study with single centre analysis is proposed in which clinicians and families are invited to choose either of the agreed regimens, usually starting at 11 years. We hypothesise that pubertal induction with transdermal estradiol will result in better outcomes for some key parameters. The primary outcome measure chosen is height gain during the induction period. Analysis: Assessment of the demographics and drop-out rates of patients choosing either oral or transdermal preparations; and appropriate analysis of outcomes including pubertal height gain, final height, liver enzyme and lipid profile, adherence/acceptability, cardiovascular health, including systolic and diastolic blood pressure and aortic root diameter and bone health. Conclusion: The proposed model of prospective data collection according to internationally agreed protocols aims to break the current impasse in obtaining evidence-based management for TS and could be applied to other rare paediatric endocrine conditions.

Published
2019
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2. Genesis of two most prevalent PROP1 gene variants causing combined pituitary hormone deficiency in 21 populations.

Author

Dusatkova P, Pfäffle R, Brown MR, Akulevich N, Arnhold IJ, Kalina MA, Kot K, Krzisnik C, Lemos MC, Malikova J, Navardauskaite R, Obermannova B, Pribilincova Z, Sallai A, Stipancic G, Verkauskiene R, Cinek O, Blum WF, Parks JS, Austerlitz F, and Lebl J

Subjects
Humans, Prevalence, Software, Genetic Predisposition to Disease, Haplotypes genetics, Homeodomain Proteins genetics, Hypopituitarism genetics, Mutation genetics
Abstract

Two variants (c.[301_302delAG];[301_302delAG] and c.[150delA];[150delA]) in the PROP1 gene are the most common genetic causes of recessively inherited combined pituitary hormones deficiency (CPHD). Our objective was to analyze in detail the origin of the two most prevalent variants. In the multicentric study were included 237 patients with CPHD and their 15 relatives carrying c.[301_302delAG];[301_302delAG] or c.[150delA];[150delA] or c.[301_302delAG];[ 150delA]. They originated from 21 different countries worldwide. We genotyped 21 single-nucleotide variant markers flanking the 9.6-Mb region around the PROP1 gene that are not in mutual linkage disequilibrium in the general populations--a finding of a common haplotype would be indicative of ancestral origin of the variant. Haplotypes were reconstructed by Phase and Haploview software, and the variant age was estimated using an allelic association method. We demonstrated the ancestral origin of both variants--c.[301_302delAG] was carried on 0.2 Mb-long haplotype in a majority of European patients arising ~101 generations ago (confidence interval 90.1-116.4). Patients from the Iberian Peninsula displayed a different haplotype, which was estimated to have emerged 23.3 (20.1-29.1) generations ago. Subsequently, the data indicated that both the haplotypes were transmitted to Latin American patients ~13.8 (12.2-17.0) and 16.4 (14.4-20.1) generations ago, respectively. The c.[150delA] variant that was carried on a haplotype spanning about 0.3 Mb was estimated to appear 43.7 (38.4-52.7) generations ago. We present strong evidence that the most frequent variants in the PROP1 gene are not a consequence of variant hot spots as previously assumed, but are founder variants.

Published
2016
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3. A novel role for thyroid hormone receptor beta in cellular radiosensitivity.

Author

Matsuse M, Saenko V, Sedliarou I, Rogounovitch T, Nakazawa Y, Mitsutake N, Akulevich N, Namba H, and Yamashita S

Subjects
Animals, COS Cells, Cell Line, Cell Line, Tumor, Cell Survival radiation effects, Chlorocebus aethiops, Gene Transfer Techniques, Humans, Mutation, Thyroid Hormone Receptors beta biosynthesis, Thyroid Hormone Receptors beta genetics, Gamma Rays, Radiation Tolerance, Thyroid Hormone Receptors beta physiology
Abstract

Thyroid hormone receptors (THRs) widely govern cell growth, differentiation and metabolism acting in a ligand- and cofactor-dependent manner to modulate tissue-specific gene expression. Given a large variety of genes regulated by THRs and multiplicity of cellular processes potentially influenced by THRs, we addressed the role of THRB (thyroid hormone receptor beta) in cellular radiosensitivity. Wild-type and mutant THRB were overexpressed in several cell lines using an adenovirus-mediated gene delivery and their effects were examined after cell exposure to gamma-rays. Wild-type THRB decreased clonogenic survival of the cell lines with low levels of endogenous THRB, retarded their growth and synergized with radiation in decreasing proliferative potential and promoting cellular senescence. These changes were accompanied by the accumulation of p21 (CDKN1A, CIP1, WAF1) and p16 (CDKN2A, INK4a) inhibitors of cyclin-dependent kinases and by the decrease of Rb (retinoblastoma protein) phosphorylation. Mutant THRB produced a radioprotective effect, attenuated radiation-induced growth inhibition and cellular senescence. The results suggest that THRB may modulate cellular radiosensitivity and stress-induced senescence.

Published
2008
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