Роль галектина-1 в регуляции гомеостаза Т-лимфоцитов

Fault in T-lymphocytes homeostasis leads to different diseases with poor or vise versa strong immune response. So it seems to be interesting to research molecules of T-cell cooperation to develop new more effective therapeutic methods. Important factor modulating T-cell activity is galectin-1 which takes part in multiply process of cell biology — regulation of cell maturation, migration, signal transduction, functional ability and apoptosis.Нарушение гомеостаза Т-лимфоцитов может приводить к развитию заболеваний, связанных с недостаточной активностью или, напротив, гиперчувствительностью иммунной системы. В связи с этим особый интерес представляет исследование молекул, участвующих в Т-клеточной кооперации, с целью разработки более эффективных терапевтических методов. Важным фактором модуляции функциональной активности Т-лимфоцитов является галектин-1, который вовлечен в многочисленные процессы жизнедеятельности клеток — регуляцию клеточного цикла, миграцию, передачу межклеточных сигналов, выполнение эффекторных функций и реализацию апоптоза

СИСТЕМА ГЛУТАТИОНА УЧАСТВУЕТ В РЕГУЛЯЦИИ АПОПТОЗА ОПУХОЛЕВЫХ КЛЕТОК

The research objective is to determine the role of the gluthatione system components in realization of the receptor pathway of Jukart tumor cell apoptosis.Apoptosis realization using FITC-labeled annexin V and propidium iodide as well as the amount of TNF R1- and Fas-presenting cells has been evaluated by flow cytofluorometry; activity caspase-3 registered a spektroflyuorimetrichesky method. The concentration of reduced and oxidated gluthatione has been determined by spectrophotometry.The material for the research was intact Jukart tumor cells and the ones incubated in the presence of a selective inhibitor of the key gluthatione synthesis enzyme – buthionine-sulfoximine.The research has shown that the gluthatione system plays an important regulatory role in activation of the receptor pathway of Jukart tumor cell apoptosis.The gluthatione system components are targets for activation of programmed cell death in tumor growth.Цель исследования – выявить роль компонентов системы глутатиона в реализации рецепторного пути апоптоза опухолевых клеток линии Jurkat.Оценку реализации апоптоза проводили методом проточной цитофлюориметрии с использованием FITS-меченного аннексина V и пропидия иодида, количества TNF R1- и Fas-презентирующих клеток; активность каспазы-3 регистрировали спектрофлюориметрическим методом. Определение содержания восстановленного и окисленного глутатиона осуществляли спектрофотометрическим методом.Материалом для исследования служили опухолевые клетки линии Jurkat: интактные и инкубированные в присутствии селективного ингибитора ключевого фермента синтеза глутатиона – бутионин-сульфоксимина.Исследование показало, что система глутатиона играет важную регуляторную роль в активации рецепторного пути апоптоза опухолевых клеток линии Jurkat.Компоненты системы глутатиона являются мишенями для активации программированной гибели при опухолевом росте

Роль внутриклеточных газовых трансмиттеров сульфида водорода и оксида азота в регуляции апоптоза нормальных и бласттрансформированных клеток

Investigation of influence of gases nitric oxide and hydrogen sulfide on apoptotic cell death of Jurlat cells and mononuclear leucocytes of healthy donors was conducted. It was shown that 100 mmol sodium nitroprussidi increased the apoptosis of T lymphoblast leukemia cells after 15’ incubation. 10 and 100 mmol donor of hydrogen sulfide caused apoptotic death of Jurkat cells after 15’ incubation. 15’ exposure of nitric oxide and hydrogen sulfide donors did not lead to the changes of cell death of mononuclear leucocytes. Gaseous transmitters NO and H2S increased necrosis of Jurkat cells and mononuclear leucocytes after 24 h incubation with the appropriate gase’s donor.Проведено исследование влияния доноров газов оксида азота и сульфида водорода на апоптотическую гибель клеток линии Jurkat и мононуклеарных лейкоцитов, полученных у здоровых доноров. Показано, что нитропруссид натрия в концентрации 100 ммоль вызывал апоптоз клеток Т-лимфобластной лейкемии после 15 мин инкубации. Донор сульфида водорода усиливал апоптотическую гибель клеток линии Jurkat при использовании его в концентрациях 10 и 100 ммоль. Воздействие доноров газов оксида азота и сульфида водорода в течение 15 мин в тех же концентрациях не сопровождалось изменениями апоптотической гибели мононуклеарных лейкоцитов, полученных у здоровых доноров. Газовые трансмиттеры NO и H2S вызывали некроз клеток линии Jurkat и мононуклеарных лейкоцитов после 24 ч инкубации клеток c соответствующими донорами газов

COGNITIVE IMPAIRMENT IN MULTIPLE SCLEROSIS: ASSOCIATION WITH THE ACTIVITY OF INFLAMMATORY PROCESS AND SEVERITY OF DISABILITY

Background: Multiple sclerosis is the most common neurological disease leading to disability in young and productive patients. One of available methods of control over the course of the disease and detection of its progression is neuropsychological testing. However, selection of the most informative tests, as well as the search for interpretation of their results is still ongoing.Aim: To study cognitive functions in multiple sclerosis patients depending on the disease activity and degree of disability.Materials and methods: Fifty patients with multiple sclerosis were evaluated during their remissions and 15 of them were additionally assessed during an exacerbation. During neuropsychological testing a computer test “Selection of figures” was used for assessment of attention, productivity, frontal functions and visual neglect. We studied potential dependency of the parameters obtained from degree of disability and disease stage (exacerbation or remission). The control group comprised 12 healthy subjects.Results: Compared to healthy subjects, the multiple sclerosis patients had a prolonged time of test performance, decreased learning, and statistically significant decrease of the working efficacy (p < 0.05). During an attack, there was a decreased conceptualization (48 answers compared to 51.5 at remission stage); more than 3-fold (from 1,3 to 4,4) increase in the number of figures missed in one visual field, that could indirectly indicate visual neglect. Also, changes in frontal functions were noted as a tendency to almost 2-fold higher numbers of perseverative answers, more frequent categorical escape and learning abnormality. There was a positive correlation between expanded disability scale score (EDSS) and working efficacy (r = 0.453, p = 0.001), and a negative correlation between EDSS and mental stability (r = 0.4055, p = 0.0035).Conclusion: Patients with multiple sclerosis had abnormal rate and accuracy of test performance, compared to those in healthy subjects. During an exacerbation of the disease, there was a deterioration of the parameters compared to those registered in the remission. Also, a negative association with disease severity assessed by EDSS, was found. The data obtained documents feasibility of the computer test “Selection of figures” for dynamic control in multiple sclerosis patients

ASSOCIATIONS OF INTERFERON GENE POLYMORPHISMS OAS-1, OAS-3, PKR WITH CHRONIC VIRAL HEPATITIS C

Abstract. Present work is devoted to analyzing possible associations of single-nucleotide gene polymorphisms (SNPs) with liver pathology in patients with chronic hepatitis C. SNP genotypes and allele frequencies were identified for some genes of interferon system, i.e., oligoadenilatsynthetase-1 (-1A/G), oligoadenilatsynthetase-3 (+1314C/T), and protein kinase R (+244A/G), using DNA samples from healthy donors and patients with chronic hepatitis C representing population of Tomsk and Tomsk Region. An association has been shown between SNPs of oligoadenilatsynthetase-1 and protein kinase R genes, and clinical activity of inflammatory process in the liver, as well as an impact of certain SNPs of protein kinase R and oligoadenilatsynthetase-3 genes upon fibrogenesis. (Med. Immunol., 2011, vol. 13, N 1, pp 93-100

ASSESSMENT OF COLOR VISION FOR DIAGNOSIS AND DYNAMIC MONITORING OF MULTIPLE SCLEROSIS

Background: Multiple sclerosis is regarded as the most frequent cause of neurological disability. Visual disturbances are common and may be due to pathology of retina, optic nerve and cerebral conduction tracts (optic tract). Routine methods of assessment of visual function are insufficient in diagnosing some visual problems including color vision disturbances. Aim: To assess color vision in patients with multiple sclerosis. Materials and methods: We examined 110 patients (age > 18 years old) with previously diagnosed multiple sclerosis. Neurological status was assessed using functional scales; results of neuroimaging, medical records and history were taken into account. Color vision was examined using Farnsworth dichotomous test. Control group included 20 healthy volunteers (8 men, 12 women, mean age 29.1 ± 1.4 years old). Results: In patients with multiple sclerosis, color vision defects were significantly more prevalent compared to the control group (89.1% vs. 65%, p < 0.05). Deuteranopia was found in 18.6% of patients with multiple sclerosis, protanopia in 17.3%, tritanopia in 7.3% of patients. Significant color vision defects positively correlated with disability level of the Expanded Disability Status Scale (EDSS) and were independent of disease duration and history of retrobulbar neuritis. Conclusion: In patients with multiple sclerosis, color vision defects were associated with the activity of pathological process. Severity of neurological disability level estimated by EDSS positively correlated with visual disturbances. Thus, Farnsworth dichotomous test may be recommended for dynamic monitoring of multiple sclerosis

Molecular genetics of follicular cell thyroid carcinoma

Thyroid cancer is the most frequent endocrine malignancy. In the most cases thyroid cancer arises from follicular cells. Diagnosis of the cancer is based on the cytological analysis of fine needle aspiration biopsy of thyroid nodes. But the accuracy of the cytological diagnosis is about 80% that leads to the false positive and false negative cases and wrong strategy of treatment. Identification of genetic and epigenetic markers in the biopsies will allow to improve diagnostic accuracy. This article describes mutations, aberrant DNA methylation and abnormal microRNA expression constituting the core of molecular genetics of follicular cell thyroid cancer. The mutations given in the article includes point mutations, fusions and copy number variation. Besides frequent and well described driver mutations in genes of МАРK, PI3K/Akt and Wnt signaling pathways, as well as TP53 and TERT genes, we introduce here less frequent mutations appeared in the literature during the past two years. In addition the article contains examples of diagnostic panels applying these markers