Identification and characterization of LMX1B target genes

Mutations in the LMX1B gene are associated with a rare autosomal-dominant disorder called nail-patella syndrome which affects limbs, eyes, brain and kidneys. The main LMX1B targets in kidneys are the foot processes and slit diaphragms of podocytes. In search for the genes which are regulated by LMX1B, microarray studies on glomeruli isolated from inducible podocyte-specific Lmx1b knock-out mice were performed. This analysis revealed a significant increase in the mRNA levels of several genes compared to control mice. For further investigation three promising LMX1B target genes were chosen: Abra (Actin-binding Rho-activating protein), Arl4c (ADP-ribosylation factor-like 4C) and Crct1 (Cystein-rich C-terminal 1). The binding of LMX1B to its target genes is mediated by the central homeodomain which specifically recognizes so-called FLAT (FAR linked AT-rich) elements. Bioinformatic studies of promoter fragments of the putative LMX1B target genes led to the identification of LMX1B binding elements within the ABRA and ARL4C promoter regions which were then analyzed using luciferase reporter assays. Their importance was verified by site-directed mutagenesis studies. The subcellular and ultrastructural localization of the proteins under investigation by confocal and electron microscopy suggested their functional involvement with the actin cytoskeleton. Further studies on the putative LMX1B targets revealed that Abra, Arl4c and Crct1 lead to the increased formation of F-actin. The data obtained suggest a possible role of the putative LMX1B target genes in the dysregulation of the actin cytoskeleton by increasing its stiffness. In addition to the main topic of this thesis the role of LMX1B in the regulation of cell-matrix adhesion dynamics was investigated using fluorescence recovery after photobleaching (FRAP). These studies demonstrated for the first time that the protein turnover of α-actinin-1 and actin, but not α-actinin-4, was notably affected by the inactivation of Lmx1b. Taken together, the results reported in the present thesis demonstrated the role of the putative LMX1B target genes in the regulation of the actin cytoskeleton, as well as the role of LMX1B in the regulation of cell-matrix adhesion dynamics

Сравнение топометрических показателей селезенки по данным ультразвукового метода исследования

Objective: to determine the ratio of the linear dimensions of the spleen and measuring the area for the standardization of research protocols and to compare over time. Materials and methods. 500 patients who underwent ultrasound of the spleen were examined. The length, width and area were measured. The mean age was 40.5 ± 7.3 years. Men in the study were 196 (39.2%) women - 304 (60.8%) Results. Direct dependence of increase in the linear sizes and the area of a spleen is revealed. Increasing the length of more than 13 cm always indicative of splenomegaly. However, the length in the range of 10.0 to 13.0 cm can fit both normal size and a significant increase even. In this connection, it is recommended to contentious matters an extra dimension or width or area of the spleen for subsequent monitoring of the dynamics of change. Conclusion. Measurement of the topometric indicators of the spleen is an important prognostic sign. It is recommended to measure as the linear dimensions and area of the largest cross-section for ease of comparison of the data.Цель исследования: определить соотношение линейных размеров селезенки и измерения площади максимального среза для стандартизация протоколов исследования и возможности сравнения показателей в динамике. Материал и методы. Обследованы 500 пациентов (мужчин - 196 (39,2%), женщин - 304 (60,8%), средний возраст 40,5 ± 7,3 года), которым проведено УЗИ селезенки. Измеряли длину, ширину и площадь максимального среза. Результаты. Выявлена прямая зависимость увеличения линейных размеров и площади селезенки. При длине селезенки 10,0 см независимо от ее толщины размеры органа будут в пределах нормы. Увеличение длины более 13 см всегда свидетельствует о спленомегалии. Однако значение длины в диапазоне от 10,0 до 13,0 см может соответствовать как нормальным размерам, так и увеличению органа, даже значительному. В связи с этим в спорных вопросах рекомендуется дополнительное измерение ширины селезенки или площади для последующего контроля динамики изменений. Заключение. Измерение топометрических показателей селезенки является важным прогностическим признаком. Рекомендуется проводить измерение как линейных размеров, так и площади наибольшего сечения для удобства сопоставления данных

Results of adolescent health risk assesment on exposure to habitat water peroral factor in conditions of a large industrial city

Results of the non-carcinogenic risk assessment on ingestion of chemical substances with drinking water showed that the risk value corresponded to the allowable level of the non-carcinogenic risk (HQ ( 1) for the major part of elements in all zones. The excess of the allowable level is observed only in oil products in the 1st zone (2.05) and the 4th zone (1.04). However, the total hazard index (HI) on combined peroral ingestion of chemical compounds and elements with drinking water in selected zones of the city of Kazan implies a low risk level for adolescents living in the 1st and the 4th zones (3.7 and 3.59) correspondingly, and is dangerous for health. According to the results of analysis carried out in all zones, the following basic critical organs and systems were identified: blood, CNS, kidneys, endocrine system, cardiovascular system, skeletal system and teeth. The total hazard indices in the 1st and the 4th zones deserve particular attention

Risk assessment of the rural population health from exposure to polluted food products

In the diet of the rural population, milk, dairy products, meat and meat products, fish, bread, and bread products make the largest contribution to the exposition of cadmium, arsenic, and mercury. The cardiovascular, hormonal, central nervous, immune, reproductive systems, blood, and kidneys are most at risk. Non-carcinogenic risk for imported food products is determined by the systems: Blood, hormonal, central nervous, and reproductive. Materials and Methods: Statistical analysis of the obtained data was implemented operating system Windows 2007 with the application of standard application program packages Excel 2007 and "Statistics v.6.0". Result and Discussion: Comparative analysis of the obtained data revealed that the Republic of Tatarstan had higher indices in the content of pollutants in the fruit and vegetable products

Ультразвуковое исследование с контрастным усилением: терминология, технические и методологические аспекты

The active implementation in practice of ultrasound contrast agents opens up new possibilities in the differential diagnosis of focal changes in various organs and tissues. Official year and a half experience in the domestic application of this technique requires the primary analysis, synthesis, systematization of chaotic research to determine the future direction of the study and implementation of new technology to the clinic. Objective. To analyze the technical and methodological aspects of the use of ultrasound contrast agents for various inflammatory and neoplastic diseases. Materials and methods. 183 ultrasound examinations with contrast enhancement at 7 state medical clinics from January 2015 to March 2016 were conducted. Zones of interest in various diseases were: eye, superficial tissue, abdominal organs (liver, pancreas, spleen, duodenum), retroperitoneal area (kidney, adrenal gland, non-organic tumor,), prostate gland. Results. New terminology to describe the changes was offered identified by ultrasound with contrast enhancement based on the analysis of the research, the technical aspects of implementation and nuances of technique of contrast enhancement of different organs and tissues were described. Conclusion. Ultrasonography with contrast enhancement provides a greater amount of information for the differential diagnosis of formations of various localization. Compliance with the general principles of the methodology and consistency in the description of the identified changes will enable to compare data from different medical institutions, to create a joint database for more in-depth study of the problem.Активное внедрение в практику ультразвуковых контрастных средств открывает новые возможности в дифференциальной диагностике очаговых изменений различных органов и тканей. Официальный полуторагодовой отечественный опыт применения данной методики требует первичного анализа, обобщения, систематизации хаотичных исследований для определения дальнейших направлений изучения и внедрения в клинику новой технологии. Цель исследования: проанализировать технические и методологические аспекты применения ультразвуковых контрастных средств при различных воспалительных и опухолевых заболеваниях. Материал и методы. С января 2015 г по март 2016 г. в 7 медицинских государственных учреждениях было проведено 183 ультразвуковых исследования (УЗИ) с контрастным усилением. Зонами интереса при различных заболеваниях были: глаза, поверхностнорасположенные ткани, органы брюшной полости (печень, поджелудочная железа, селезенка, двенадцатиперстная кишка), забрюшинного пространства (почки, надпочечники, неорганные опухоли), предстательная железа. Результаты. На основании анализа проведенных исследований была предложена новая терминология для описания изменений, выявленных при УЗИ с контрастным усилением, описаны технические аспекты, нюансы выполнения методики при контрастировании различных органов и тканей. Выводы. УЗИ с контрастным усилением позволяет получить больший объем информации для проведения дифференциальной диагностики образований различной локализации. Соблюдение общих принципов проведения методики и согласованность в описании выявленных изменений позволят сопоставлять данные различных медицинских учреждений, создать совместные базы данных для более глубокого изучения проблемы

Возможности лучевой диагностики в органосохраняющем лечении больного раком единственной почки с рецидивом (клиническое наблюдение)

Kidney cancer - one of the most often found urological tumors making 2% of all malignant new growths. The main method of a cancer therapy of a kidney is surgical. Removal of primary center increases survival at all stages of a dis ease. The best results at the first stage are yielded by a nephrectomy (full removal of the affected kidney); however if the sizes of a tumor are small (or a kidney only one, or the bilateral cancer of kidneys is diagnosed), apply organ-preserving treatment - a kidney resection. The resection of a kidney provides survival indicators, comparable with a nephrectomy, without recurrence for tumorsРак почки - одна из наиболее часто встречающихся урологических опухолей, составляющая 2% от всех злокачественных новообразований. Основным методом лечения рака почки является хирургический. Удаление первичного очага увеличивает выживаемость на всех стадиях заболевания. Наилучшие результаты на первой стадии даёт нефрэктомия (полное удаление пораженной почки); однако если размеры опухоли невелики (либо почка всего одна, или же диагностирован двусторонний рак почек), применяют органосохраняющее лечение - резекцию почки. Резекция почки обеспечивает сравнимые с нефрэктомией показатели выживаемости без рецидива для опухоле

C9ORF72 hexanucleotide repeat expansion in ALS patients from the Central European Russia population

Cohorts of amyotrophic lateral sclerosis (ALS) patients and control individuals of Caucasian origin from the Central European Russia (Moscow city and region) were analyzed for the presence of hexanucleotide repeat GGGGCC expansion within the first intron of the C9ORF72 gene. The presence of a large (>40) repeat expansion was found in 15% of familial ALS cases (3 of 20 unrelated familial cases) and 2.5% of sporadic ALS cases (6 of 238) but in none of control cases. These results suggest that the frequency of C9ORF72 hexanucleotide repeats expansions in the Central Europea