Incorporation and localisation of ganglioside GM3 in human intimal atherosclerotic lesions

AbstractImmunohistochemical examination showed that sections of intimal atherosclerotic plaques contained cells and cell clusters as well as areas of extracellular matrix specifically stained with antibodies against ganglioside GM3. No immunohistochemical staining was observed in areas bordering the plaques where there was no histological evidence of atherosclerosis. To determine whether the ganglioside GM3 deposits in the intimal plaques derived directly from plasma or were synthesised by intimal cells, intimal plaque and plasma LDL were assayed for ganglioside GM3 fatty acid composition. This assay showed that more than 50% of the fatty acids of GM3 isolated from both atherosclerotic and normal intima are either minor fatty acids or those absent from LDL GM3. We conclude that the GM3 deposits present in intimal plaque arise in intimal cells and do not derive from plasma LDL

The Immune Cell Composition in Barrett's Metaplastic Tissue Resembles That in Normal Duodenal Tissue

BACKGROUND AND OBJECTIVE: Barrett's esophagus (BE) is characterized by the transition of squamous epithelium into columnar epithelium with intestinal metaplasia. The increased number and types of immune cells in BE have been indicated to be due to a Th2-type inflammatory process. We tested the alternative hypothesis that the abundance of T-cells in BE is caused by a homing mechanism that is found in the duodenum. PATIENTS AND METHODS: Biopsies from BE and duodenal tissue from 30 BE patients and duodenal tissue from 18 controls were characterized by immmunohistochemistry for the presence of T-cells and eosinophils(eos). Ex vivo expanded T-cells were further phenotyped by multicolor analysis using flowcytometry. RESULTS: The high percentage of CD4(+)-T cells (69±3% (mean±SEM/n = 17, by flowcytometry)), measured by flowcytometry and immunohistochemistry, and the presence of non-activated eosinophils found in BE by immunohistochemical staining, were not different from that found in duodenal tissue. Expanded lymphocytes from these tissues had a similar phenotype, characterized by a comparable but low percentage of αE(CD103) positive CD4(+)cells (44±5% in BE, 43±4% in duodenum of BE and 34±7% in duodenum of controls) and a similar percentage of granzyme-B(+)CD8(+) cells(44±5% in BE, 33±6% in duodenum of BE and 36±7% in duodenum of controls). In addition, a similar percentage of α4β7(+) T-lymphocytes (63±5% in BE, 58±5% in duodenum of BE and 62±8% in duodenum of controls) was found. Finally, mRNA expression of the ligand for α4β7, MAdCAM-1, was also similar in BE and duodenal tissue. No evidence for a Th2-response was found as almost no IL-4(+)-T-cells were seen. CONCLUSION: The immune cell composition (lymphocytes and eosinophils) and expression of intestinal adhesion molecule MAdCAM-1 is similar in BE and duodenum. This supports the hypothesis that homing of lymphocytes to BE tissue is mainly caused by intestinal homing signals rather than to an active inflammatory response

Australian clinical practice guidelines for the diagnosis and management of Barrett's esophagus and early esophageal adenocarcinoma

Author version made available following 12 month embargo from date of publication according to publisher copyright policy.Barrett's esophagus (BE), a common condition, is the only known precursor to esophageal adenocarcinoma (EAC). There is uncertainty about the best way to manage BE as most people with BE never develop EAC and most patients diagnosed with EAC have no preceding diagnosis of BE. Moreover, there have been recent advances in knowledge and practice about the management of BE and early EAC. To aid clinical decision making in this rapidly moving field, Cancer Council Australia convened an expert working party to identify pertinent clinical questions. The questions covered a wide range of topics including endoscopic and histological definitions of BE and early EAC; prevalence, incidence, natural history, and risk factors for BE; and methods for managing BE and early EAC. The latter considered modification of lifestyle factors; screening and surveillance strategies; and medical, endoscopic, and surgical interventions. To answer each question, the working party systematically reviewed the literature and developed a set of recommendations through consensus. Evidence underpinning each recommendation was rated according to quality and applicability

Topographical and Biological Evidence Revealed FTY720-Mediated Anergy-Polarization of Mouse Bone Marrow-Derived Dendritic Cells In Vitro

Abnormal inflammations are central therapeutic targets in numerous infectious and autoimmune diseases. Dendritic cells (DCs) are involved in these inflammations, serving as both antigen presenters and proinflammatory cytokine providers. As an immuno-suppressor applied to the therapies of multiple sclerosis and allograft transplantation, fingolimod (FTY720) was shown to affect DC migration and its crosstalk with T cells. We posit FTY720 can induce an anergy-polarized phenotype switch on DCs in vitro, especially upon endotoxic activation. A lipopolysaccharide (LPS)-induced mouse bone marrow-derived dendritic cell (BMDC) activation model was employed to test FTY720-induced phenotypic changes on immature and mature DCs. Specifically, methods for morphology, nanostructure, cytokine production, phagocytosis, endocytosis and specific antigen presentation studies were used. FTY720 induced significant alterations of surface markers, as well as decline of shape indices, cell volume, surface roughness in LPS-activated mature BMDCs. These phenotypic, morphological and topographical changes were accompanied by FTY720-mediated down-regulation of proinflammatory cytokines, including IL-6, TNF-α, IL-12 and MCP-1. Together with suppressed nitric oxide (NO) production and CCR7 transcription in FTY720-treated BMDCs with or without LPS activation, an inhibitory mechanism of NO and cytokine reciprocal activation was suggested. This implication was supported by the impaired phagocytotic, endocytotic and specific antigen presentation abilities observed in the FTY720-treated BMDCs. In conclusion, we demonstrated FTY720 can induce anergy-polarization in both immature and LPS-activated mature BMDCs. A possible mechanism is FTY720-mediated reciprocal suppression on the intrinsic activation pathway and cytokine production with endpoint exhibitions on phagocytosis, endocytosis, antigen presentation as well as cellular morphology and topography

Directions of Development of National Innovation System

Purpose: to study the feasibility of building a national innovation system on the principles of rational self-sufficiency of the domestic economy. Methods: during research following methods were applied: comparative and correlative analysis, correlations, decomposition, and economic analysis. As an analytical and evidence materials used for international comparisons, as well as normative-legal documents regulating innovative activities in the Russian Federation. Results: international experience suggests that the most common way of ensuring innovative development of the country is to attract investments in advanced technological States. Passed a similar path in Germany, Japan, South Korea, and China. However, in today's Russia, such a solution is impossible for two reasons. The first is the already accumulated level of foreign investment in the industry, exceeding the threshold of national security. And the second is the reluctance to contribute to the economic progress in our country, conducting an independent policy on the part of developed States of the world under US control. In these circumstances, the only way is to build a national innovation system (NIS), relying primarily on its own strength, especially because all the necessary prerequisites and resources are in place. Conclusions and Relevance: results of the study indicate the presence of necessary and sufficient conditions for the formation of a national innovation system focused on the use of internal potential of economy of the Russian Federation. The challenge is in choosing the right principles of its construction

Forecasting and Strategic Goal-Setting Mechanisms of Social-Economic Development of the Russian Federation

In this article, the authors carried out the analysis of principle implementation and application efficiency of strategic forecasting and strategic goal-setting mechanisms in the field of social-economic development. According to the authority distribution in the state management system, we propose to optimize the set of basic documents of strategic planning. Taking into account the criteria of necessity and sufficiency, as well as the existing mechanisms of state management, the scope of regulation, purpose and functional tasks of strategic planning documents at the federal and sectoral levels are specified

Направления развития национальной инновационной системы

Purpose: to study the feasibility of building a national innovation system on the principles of rational self-sufficiency of the domestic economy. Methods: during research following methods were applied: comparative and correlative analysis, correlations, decomposition, and economic analysis. As an analytical and evidence materials used for international comparisons, as well as normative-legal documents regulating innovative activities in the Russian Federation. Results: international experience suggests that the most common way of ensuring innovative development of the country is to attract investments in advanced technological States. Passed a similar path in Germany, Japan, South Korea, and China. However, in today's Russia, such a solution is impossible for two reasons. The first is the already accumulated level of foreign investment in the industry, exceeding the threshold of national security. And the second is the reluctance to contribute to the economic progress in our country, conducting an independent policy on the part of developed States of the world under US control. In these circumstances, the only way is to build a national innovation system (NIS), relying primarily on its own strength, especially because all the necessary prerequisites and resources are in place. Conclusions and Relevance: results of the study indicate the presence of necessary and sufficient conditions for the formation of a national innovation system focused on the use of internal potential of economy of the Russian Federation. The challenge is in choosing the right principles of its construction. Цель: Обоснование целесообразности построения национальной инновационной системы на принципах рациональной самодостаточности отечественной экономики. Методология проведения работы: В ходе исследования применялись методы сравнительного и корреляционного анализа, декомпозиции и экономического анализа. Аналитическую и доказательную базу исследования составили материалы международных сопоставлений, а также нормативно-правовые документы, регламентирующие инновационную деятельность в РФ. Результаты работы: Международный опыт свидетельствует о том, что наиболее распространенным способом обеспечения инновационного развития страны является привлечение инвестиций «продвинутых» в технологическом плане государств. Подобный путь прошли Германия, Япония, Южная Корея, Китай. Однако для современной России подобное решение невозможно по двум причинам. Первая состоит в уже накопленном уровне иностранных инвестиций в промышленности, превышающем порог национальной безопасности. И вторая – в нежелании содействовать экономическому прогрессу в нашей стране, проводящей самостоятельную политику, со стороны развитых государств мира, находящихся под контролем США. В этих условиях единственный выход состоит в построении национальной инновационной системы (НИС) с опорой преимущественно на собственные силы, тем более, что все необходимые предпосылки и ресурсы для этого имеются. Выводы: Результаты исследования свидетельствуют о наличии необходимых и достаточных условий для формирования национальной инновационной системы, ориентированной на использование внутреннего потенциала экономики РФ. Задача состоит лишь в правильном выборе принципов ее построения.

The comparative study of common carotid intima-media thickness in Russian and Italian high-risk individuals

Objectives: In comparison with Europeans Russian population shows enormously high levels of cardiovascular mortality and morbidity. A recent European study (IMPROVE) has revealed the existence of a geographical gradient in subclinical atherosclerosis which parallels with the North-to South geographical gradient in cardiovascular mortality described in the WHO Europe database. This study was kept to characterize the variability of common carotid intima-media thickness (cIMT) in selected high-risk population sample recruited in Moscow (n=407) and Milan (n=435), and to investigate the hypothesis of West-to-East cIMT gradient, as well as to elucidate the role of cardiovascular risk factor in between-population cIMT variability. Methods: Asymptomatic men and women (55-79 yrs) with at least three cardiovascular risk factors were eligible. Different from the IMPROVE Study, ultrasonic scans were taken from the distal centimeter of common carotid arteries only. Quantification of cIMT was performed in Monzino Cardiology Center (Milan, Italy) by a qualified reader using Mat'h software. Results: The comparative analysis has revealed that the mean (95% CI) cIMT value was significantly higher in Moscow - 0.82 (0.81-0.85) mm than in Milan - 0.73 (0.72-0.74) mm (p<0.001). Moscow study participants have higher prevalence of arterial hypertension, blood pressure, total and HDL cholesterol and triglycerides, and take less medication. However, these differences explains only 16% between-population difference in cIMT variability. Decision tree analysis has revealed that the site of residence has a decisive impact on the observed difference in cIMT variability. The association between cIMT and the standardized mortality ratio for IHD reported in the WHO European database is non-linear (R-square 0.86, p<0.001 for logarithmic correlation). Conclusion: Cardiovascular mortality in Russia is only partially explained by a higher atherosclerotic risk profile; genetic and environmental factors should be strongly involved in between-population difference in cIMT variability, which can help explaining the striking difference in cardiovascular mortality between European and Russian populations