scholarly journals GENETIC POLYMORPHISM OF RETROPERITONEAL MYXOID LIPOSARCOMA

2020 ◽  
Vol 19 (3) ◽  
pp. 89-96
Author(s):  
A. Yu. Volkov ◽  
V. M. Safronova ◽  
S. N. Nered ◽  
L. N. Lyubchenko ◽  
I. S. Stilidi
Keyword(s):  
Molecular Genetic ◽  
Myxoid Liposarcoma ◽  
Molecular Genetic Analysis ◽  
Term Treatment ◽  
Missense Mutations ◽  
Synonymous Mutations ◽  
Erbb2 Gene ◽  
Long Term Treatment ◽  
Wide Range ◽  
Next Generation Sequencing Ngs

Objective: to detect new molecular genetic markers and therapeutic targets in retroperitoneal myxoid liposarcoma.Material and Methods. DNA samples isolated from tumor tissue and obtained from formalinfixed paraffin-embedded (FFPE) slides were used. DNA was extracted using the GeneRead DNA FFPE Kit (50) (Qiagen). High-throughput next generation sequencing (NGS) using the GeneReader Actionable Insights Tumor Panel (GRTP – 101X) on the QCI Analyzer version 1.1 platform (Qiagen) was used for molecular genetic analysis of 12 genes involved in carcinogenesis: KRAS, NRAS, KIT, BRAF, PDGFRA, ALK, EGFR, ERBB2, PIK3CA, ERBB3, ESR1, RAF1.Results. Targeted sequencing of retroperitoneal extra-organ myxoid liposarcoma demonstrated genetic heterogeneity. Our study was the first to describe mutations and polymorphic variants in genes, such as EGFR, PIK3CA, ALK, BRAF, ERBB2 / 3, ESR1, KIT, PDGFRA in myxoid liposarcoma.Conclusion. This study demonstrated a wide range of molecular genetic rearrangements in retroperitoneal extra-organ myxoid liposarcoma. Synonymous mutations in the EGFR (Q787Q) and PDGFRA (P567P) genes were detected in all cases (100 %). Missense mutations in the ERBB2 gene (P1170A) and synonymous mutations in the ALK (G845G) and BRAF genes were identified in 75 % of cases. Missense mutation in the PIK3CA gene (I391M) was detected in 25 % of cases. The gene polymorphisms presented in this paper are most likely involved in the carcinogenesis of retroperitoneal myxoid liposarcoma. Further studies with larger patient groups and multivariate analysis of long-term treatment results are required. 

scholarly journals Achieving Viral Suppression in 90% of People Living With Human Immunodeficiency Virus on Antiretroviral Therapy in Low- and Middle-Income Countries: Progress, Challenges, and Opportunities

2018 ◽  
Vol 66 (10) ◽  
pp. 1487-1491 ◽  
Author(s):  
Jean B Nachega ◽  
Nadia A Sam-Agudu ◽  
Lynne M Mofenson ◽  
Mauro Schechter ◽  
John W Mellors
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Suppression ◽  
Cost Effective ◽  
Term Treatment ◽  
Middle Income ◽  
Middle Income Countries ◽  
Long Term Treatment ◽  
Wide Range ◽  
Immunodeficiency Virus ◽  
Low And Middle Income

Abstract Although significant progress has been made, the latest data from low- and middle-income countries show substantial gaps in reaching the third “90%” (viral suppression) of the UNAIDS 90-90-90 goals, especially among vulnerable and key populations. This article discusses critical gaps and promising, evidence-based solutions. There is no simple and/or single approach to achieve the last 90%. This will require multifaceted, scalable strategies that engage people living with human immunodeficiency virus, motivate long-term treatment adherence, and are community-entrenched and ‑supported, cost-effective, and tailored to a wide range of global communities.

Clinical and diagnostic value of the method of chromato-mass spectrometry of microbial markers in case of damage to the oral mucosa in children by rheumatic diseases

2021 ◽  
Vol 1 (38) ◽  
pp. 49-57
Author(s):  
A. A. Skakodub ◽  
O. I. Admakin ◽  
Ad. A. Mamedov ◽  
N. A. Geppe ◽  
A. V. Simonova
Keyword(s):  
Mass Spectrometry ◽  
Oral Mucosa ◽  
Rheumatic Diseases ◽  
Modern Method ◽  
Diagnostic Value ◽  
Term Treatment ◽  
Individual Treatment ◽  
Oral Microbiota ◽  
Long Term Treatment ◽  
Wide Range

Due to the presence of a large percentage of 42.6% secondary oral infection in children with rheumatic diseases [1, 2], which arose during long-term treatment of shock and maintenance doses of anti-inflammatory therapy, it was important to study the microbiota [16, 17]. This paper for the first time applied a modern method for assessing the microbiota of various biotopes of the affected oral mucosa in children with rheumatic diseases – chromatosis-mass-spectrometry (CMSM), based on the quantitative determination of the level of markers of microorganisms: fatty acids, aldehydes, alcohols [5, 7, 10, 11]. СMSM is a highly sensitive method with a wide diagnostic spectrum. The study of a wide range of microorganisms provides new opportunities in the diagnosis of oral dysbacteriosis and increasing the effectiveness of individual treatment. The aim of the study is to improve the level of diagnosis and treatment of oral mucosal diseases in children with rheumatic diseases, through the use of chromato-mass-spectrometry of the oral microbiota.

scholarly journals Analysis of the mutational spectrum of the SLC26A4 gene and its contribution to the etiology of inherited hearing loss in the indigenous population of Southern Siberia

2020 ◽  
pp. 43-45
Author(s):  
В.Ю. Данильченко ◽  
М.В. Зыцарь ◽  
Е.А. Маслова ◽  
М.С. Бады-Хоо ◽  
И.В. Морозов ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Unknown Etiology ◽  
Southern Siberia ◽  
Pathogenic Variants ◽  
Slc26a4 Gene ◽  
Wide Range ◽  
Polymorphic Variants ◽  
Tyva Republic

Мутации в гене SLC26A4 являются частой причиной потери слуха во многих регионах мира. В работе приводятся результаты молекулярно-генетического анализа (с использованием секвенирования по Сэнгеру) последовательности гена SLC26A4, впервые проведенного в выборке пациентов с потерей слуха неустановленной этиологии (n=232) из Республик Тыва и Алтай. Установлены контрастные различия патогенетического вклада мутаций в гене SLC26A4 в этиологию нарушения слуха у коренных жителей этих географически близких регионов: 28,2% - для тувинцев и 4,3% - для алтайцев. Выявлены как уже известные, так и новые патогенные варианты, а также широкий спектр полиморфных вариантов гена SLC26A4. Mutations in the SLC26A4 gene are a common cause of hearing loss in many regions of the world. This paper presents the results of molecular genetic analysis (by Sanger sequencing) of the SLC26A4 sequence, first performed in the sample of patients with hearing loss of unknown etiology (n=232) from the Tyva Republic and the Altai Republic. Contrast differences of the pathogenic contribution of SLC26A4 mutations to the etiology of hearing impairment were revealed in the indigenous peoples of these geographically close regions: 28.2% for Tuvinians and 4.3% for Altaians. Both known and novel pathogenic variants as well as a wide range of polymorphic variants were found in the SLC26A4 gene sequence.

Marfan Syndrome

2005 ◽  
Vol 44 (04) ◽  
pp. 487-497 ◽  
Author(s):  
G. Mátyás ◽  
B. Steinmann ◽  
D. Baumgartner ◽  
C. Baumgartner
Keyword(s):  
Medical Treatment ◽  
Marfan Syndrome ◽  
Clinical Symptoms ◽  
Early Stage ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Hierarchical Cluster ◽  
Molecular Genetic Analysis ◽  
Missense Mutations ◽  
Surgical Interventions

Summary Objectives: Marfan syndrome (MFS) is an autosomal dominant inherited connective tissue disorder caused by mutations in the fibrillin-1 (FBN1) gene with variable clinical manifestations in the cardiovascular, musculoskeletal and ocular systems. Methods: Data of molecular genetic analysis and a catalogue of clinical manifestations including aortic elastic parameters were mined in order to (i) assess aortic abnormality before and during medical treatment, and to (ii) identify novel correlations between the genotype and phenotype of the disease using hierarchical cluster analysis and logistic regression analysis. A score measure describing the similarity between a patient’s clinical symptoms and a characteristic phenotype class was introduced. Results: A probabilistic model for monitoring the loss of aortic elasticity was built on merely aortic parameters of 34 patients with classic MFS and 43 control subjects showing a sensitivity of 82% and a specificity of 96%. The clinical phenotypes of 100 individuals with classical or suspected MFS were clustered yielding four different phenotypic expressions. The highest correlation was found between FBN1 missense mutations, which manifested as ectopia lentis, skeletal major and skin minor criteria, and two out of four clustered phenotypes. The probability of the presence of a missense mutation in both phenotype classes is approximately 70%. Conclusions: Monitoring of aortic elastic properties during medical treatment may serve as additional criterion to indicate elective surgical interventions. Genotype-phenotype correlation may contribute to anticipate the clinical consequences of specific FBN1 mutations more comprehensively and may be helpful to identify MFS patients at risk at an early stage of disease.

scholarly journals Gene mutations in the PI3K/Akt signaling pathway were related to immune thrombocytopenia pathogenesis

2020 ◽  
Author(s):  
Ruijie Sun ◽  
Shu-Yan Liu ◽  
Xiao-Mei Zhang ◽  
Jing-Jing Zhu ◽  
Dai Yuan ◽  
...  
Keyword(s):  
Genetic Susceptibility ◽  
Signaling Pathway ◽  
Molecular Genetic ◽  
Genomic Analysis ◽  
Akt Signaling ◽  
Molecular Genetic Analysis ◽  
Missense Mutations ◽  
Functional Connections ◽  
Molecular Features ◽  
The Impact

Abstract Immune thrombocytopenic (ITP) is an autoimmune bleeding disease with genetic susceptibility. In this research, we conducted an in-depth genomic analysis of a cohort of patients and elucidate molecular features associated with disease pathogenesis of ITP. High-molecular-weight genomic DNA was extracted from freshly frozen BMBMCs (bone marrow blood mononuclear cell) in 20 active ITP patients. After this, the samples were subjected to molecular genetic analysis by whole-exome sequencing technique (WES) then, confirmed by sanger sequencing method. The enriched signaling pathway analysis and cellular processes associated with the mutated genes was performed with gene mapping to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results of this study showed that there were 3998 missense mutations involving 2269 genes in more than 10 individuals. Unique genetic variants including PTEN, INSR and COCH were the most associated with the pathogenesis of ITP. Functional analysis revealed these mutation genes mainly affect Phosphatidylinositol 3 kinase/serine/threonine kinase B (PI3K/Akt) signaling pathways (signal transduction) and platelet activation (immune system). Our finding further demonstrates the functional connections between these variant genes and ITP. Although the substantial mechanism and the impact of genetic variation are required further investigation, the application of next generation sequencing in ITP in this paper is a valuable method to reveal the genetic susceptibility.

scholarly journals Study of Phytophthora infestans Mont. de Bary isolates in the planting of potatoes

2021 ◽  
pp. 86-91
Author(s):  
N. V. Matsishina ◽  
P. V. Fisenko ◽  
O. A. Sobko ◽  
I. V. Kim ◽  
D. I. Volkov ◽  
...  
Keyword(s):  
Phytophthora Infestans ◽  
Molecular Genetic ◽  
Microscopic Analysis ◽  
Molecular Genetic Analysis ◽  
In Vitro Cultivation ◽  
Genetic Characteristics ◽  
Potato Varieties ◽  
Phytotoxic Activity ◽  
Wide Range

Relevance. One of the most common diseases of potatoes and other nightshade family species is late blight caused by a pathogenic oomycete of the Phytophthora infestans (Mont.) de Bary. At least 100 species of phytophthora have been described in nature, affecting a wide range of plant species. The phytophthora population is heterogeneous and is represented by races, as well as different types of mating. This leads to a rapid adaptation of the pathogen and the emergence of new, more aggressive, and resistant races. Phytophthora is a parasite, the damage from which cannot be avoided within the organic farming framework. Therefore, it is particularly important to know the pathogenesis and racial composition of phytophthora in each individual region of Solanaceae cultivation.Research methodology. Differentiation and collection of material from the natural population were carried out using potato varieties with known R-genes in the genome. Isolation and introduction into the culture were carried out from leaves with the dampening chambers method, followed by cultivation on nutrient media. The pathogen was identified by microscopic analysis. Culture filtrates were obtained on the liquid nutritious medium, followed by liquid filtration and autoclaving. Phytotoxic activity was determined by the effect on the seedlings of the nightshade, grass, and pea families by the standard method. Molecular genetic analysis of the isolates was carried out by ISSR analysis; the primer, amplification mixture, and temperature profile of the reaction were selected according to the literature data; the calculation of genetic characteristics was carried out using POPGENE software packages.Results. Samples of seven Phytophthora infestans isolates were collected and introduced into culture. As a result of in vitro cultivation, morphological differences were revealed, expressed in the structure and color of the mycelium, the shape of the colonies, the nature of sporulation, the color of the reverse, and the medium under the colonies. The genetic differences of the natural phytophthora material introduced into the culture, collected from potato varieties with single resistance genes (R1, R3, R4), were revealed. Differences in the phytotoxic activity of the studied isolates' cultural filtrates were revealed. The isolated isolates demonstrate differentiation at the phenotypic, genetic and physiological levels, which allows us to speak about their belonging to races.

scholarly journals DIAGNOSIS AND OUTPATIENT TREATMENT OF CHILDREN WITH LONG QT SYNDROME: LONG-TERM OUTCOMES

2019 ◽  
Vol 8 (3) ◽  
pp. 20-28
Author(s):  
E. Yu. Emelyanchik ◽  
A. Yu. Cheremisina ◽  
E. Yu. Krasikova ◽  
S. V. Yakshanova ◽  
E. A. Ivanitsky ◽  
...  
Keyword(s):  
High Risk ◽  
Long Qt Syndrome ◽  
Clinical Status ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Long Qt ◽  
Asymptomatic Children ◽  
Wide Range ◽  
Qt Syndrome

Aim To assess the diagnostic accuracy of long QT syndrome in children and to estimate the results of the follow-up.Methods High-risk groups of children with bradycardia less than the second percentile and/or a family history of sudden death syndrome, and children with syncope diagnosed with the ECG testing were included in the study. All patients underwent routine medical examination, molecular genetic testing and were followed-up for 3,5–10 years.Results The majority of children haves transient corrected QT prolongation secondary to therapy, requiring ECG monitoring. High-risk group screening reports higher rates of idiopathic LQTS. ECG testing shows its efficiency among asymptomatic children with a normal heart rate. Patients present with syncope at the outpatient settings require the exclusion of a wide range of diseases, both congenital and acquired heart disease. The clinical status of the examined patients does not always correspond to the known LQTS variants. Molecular genetic analysis provides relevant information on the genetic heterogeneity of the disease, including new mutations, both pathological and beneficial ones.Conclusion Regardless of the presence or absence of molecular genetic confirmation of LQTS, beta blocker therapy in some cases combined with implanted cardioverterdefibrillator prevents the development of the adverse events in the long-term period and ensures normal emotional, intellectual and physical development.

scholarly journals Molecular Genetic Analysis in Patients with a Phenotype-Based Putative Diagnosis of Von Willebrand's Disease Type 1

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2820-2820
Author(s):  
Michael Steiner ◽  
Rosa Steiner ◽  
Beate Krammer-Steiner
Keyword(s):  
Genetic Analysis ◽  
Conflicts Of Interest ◽  
Direct Sequencing ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Bleeding Tendency ◽  
Missense Mutations ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease

Abstract The conclusive diagnosis of von Willebrand's disease (VWD) type 1 represents a challenging task. In addition to repeatedly performed phenotypic assessment, genetic analysis of the VWF gene may help establish the diagnosis. The aim of the present study was to assess the contribution of molecular genetic analysis in confirming the diagnosis in cases of suspected VWD type 1. Twenty-one patients (18 females, 3 males) with bleeding tendency were preliminary classified as likely or possible VWD type 1 based on phenotypic assays (VWF:Ag, VWF:RCoF < 50 % or 51-59 %, respectively) and further investigated by direct sequencing and MLPA analysis of the VWF gene. Ten different heterozygous mutations were identified in eleven patients (52 % confirmation rate). The mutation Y1584C (exon 28) was found in two unrelated patients. Most patients (9 of 11) demonstrated missense mutations in exons 20, 21, 28, 45 and 49. Newly identified mutations were K2566N (exon 45) and a 15 bp insertion predicting L168insX (exon 5). Large deletions and duplications were not detected. The results confirm the varying molecular pathology underlying VWD type 1. Molecular genetic analysis represents a useful approach to conclusively establish the diagnosis of VWD type 1 in approximately 50 % of patients with a phenotype-based preliminary diagnosis. Disclosures No relevant conflicts of interest to declare.

scholarly journals Analysis of genetic aberrations in pediatric high-grade gliomas

2020 ◽  
Vol 7 (3) ◽  
pp. 37-47
Author(s):  
M. A. Zaytseva ◽  
A. P. Shekhtman ◽  
L. I. Papusha ◽  
E. F. Valiakhmetova ◽  
L. A. Yasko ◽  
...  
Keyword(s):  
Fusion Gene ◽  
Clinical Care ◽  
Molecular Genetic ◽  
Driver Mutations ◽  
High Grade ◽  
Missense Mutations ◽  
Genetic Aberrations ◽  
Genomic Landscape ◽  
Wide Range ◽  
High Grade Gliomas

Background. High-grade gliomas are characterized by a wide range of genetic abnormalities. The heterogeneous genomic landscape of pediatric high-grade gliomas allows identifying distinct subgroups of the disease in children and young adults. Most importantly, these subgroups differ by clinical course and prognosis, as well as treatment response to standard therapy.Objective: to assess the profile of molecular genetic markers of high-grade gliomas in children.Materials and methods. In the current study, we examine the frequency of H3F3A, Hist1H3B, BRAF, IDH1 / 2 mutations, the copy number alterations of CDKN2A / 2B genes and the expression of ETV6‑NTRK3 fusion gene in a cohort of 53 pediatric high-grade gliomas.Results. Driver mutations and CDKN2A / 2B deletions were observed in 24 (45 %) and 15 (28 %) of 53 tumors, respectively. Overall, the studied high-grade gliomas harbored 41 genetic aberrations including 24 (58.5 %) somatic missense mutations, 1 (2.4 %) genetic variant of unknown clinical significance, 1 (2.4 %) oncogenic fusion gene and 15 (36.6 %) deletions of the tumor suppressor genes.Conclusion. These findings point to the importance of molecular profiling of tumors for the optimal clinical care and development of new approaches to treatment aimed at molecular targets for personalized anticancer therapies.

EFFECTS OF LONG-TERM TREATMENT AND OF LOW CONCENTRATIONS OF THYROID HORMONES ON THE OXYGEN UPTAKE OF TOAD TISSUES

1966 ◽  
Vol 36 (3) ◽  
pp. 221-229 ◽  
Author(s):  
C. C. THORNBURN ◽  
A. J. MATTY
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Uptake ◽  
Bufo Bufo ◽  
Term Treatment ◽  
Seasonal Effect ◽  
Long Term Treatment ◽  
Wide Range ◽  
Two Peaks

SUMMARY Isolated tissues of the toad Bufo bufo (urinary bladder, skin and kidney) were treated in vitro with thyroxine (T4) or tri-iodothyronine (T3) both with and without prior administration of the hormones in vivo. They were incubated at low temperature, and their oxygen consumption studied for 48 hr. Both hormones had little effect in vitro. Pretreatment with T4 in vivo usually lowered oxygen uptake; the effect of pretreatment with T3 varied. The presence of alanine in the incubating medium caused a marked increase in oxygen consumption. A seasonal effect was also found. The respiration of isolated toad bladder was stimulated by a wide range of concentrations of thyroxine in vitro, and there were two peaks of stimulation.

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