Minor histocompatibility antigen-specific cytotoxic T lymphocytes generated with dendritic cells from DLA-identical littermates

AbstractDonor cytotoxic T lymphocytes (CTL) specific for minor histocompatibility antigens (mHA) mediate the graft-versus-host effect whereas host mHA-specific CTL mediate graft rejection in the setting of major histocompatibility complex identical allogeneic hematopoietic stem cell transplantation. Development of a large animal model from which mHA-specific CTL can be isolated would accelerate translation in clinical studies to improve control of the graft-versus-host effect as well as prevention of graft rejection in sensitized hosts. The aims of the current study were to isolate mHA-specific CTL from dog leukocyte antigen-identical littermate nonsensitized recipients before transplantation, from stable mixed hematopoietic chimeras, and from dogs sensitized to mHA after graft rejection. Donor dendritic cells (DCs) were cultured from bone marrow-derived CD34+ cells and were used to stimulate recipient T lymphocytes on days 1, 10, and 20 of CTL culture. We reliably generated and expanded mHA-specific CTL ex vivo from sensitized dogs that were given a donor-specific blood transfusion to boost immune recall after graft rejection after a nonmyeloablative transplantation. The mHA-specific cytotoxicity measured by 51Cr release assay was enriched from less than 5% in the starting population of sensitized peripheral blood mononuclear cells to a median of 63% after 4 weeks in CTL culture. The expanded mHA-specific CTLs were not tissue-specific: hematopoietic cells, fibroblast, and stromal cell lines were lysed in an mHA-specific manner. Allogeneic DCs, but not peripheral blood mononuclear cells, were necessary for stimulating ex vivo expansion of mHA-specific CTL. We were unable to generate mHA-specific CTL from nonsensitized dogs before transplantation, from previously sensitized dogs but without recent recall immunization, or from stable mixed hematopoietic chimeras. We conclude that after recent in vivo sensitization, large-scale ex vivo expansion of mHA-specific CTL was feasible using allogeneic DCs. © 2003 American Society for Blood and Marrow TransplantationBiology of Blood and Marrow Transplantation 9:234-242 (2003

Physics and Chemistry of the Hydrogen Fluoride Production Process from Fluorine Containing Waste

The impact of the aluminum industry wastes on the environment is established. The resource efficient method of aluminum industry fluorine-containing wastes processing, which includes wastes oxidizing roasting to remove carbon component and the interaction of fluorine- containing particles with sulfuric acid in order to produce hydrogen fluoride, is considered. The economic and environmental effect of the proposed processing method is substantiated

Elastase-2 Knockout Mice Display Anxiogenic- and Antidepressant-Like Phenotype : Putative Role for BDNF Metabolism in Prefrontal Cortex

Several pieces of evidence indicate that elastase-2 (ELA2; chymotrypsin-like ELA2) is an alternative pathway to the generation of angiotensin II (ANGII). Elastase-2 knockout mice (ELA2KO) exhibit alterations in the arterial blood pressure and heart rate. However, there is no data on the behavioral consequences of ELA2 deletion. In this study, we addressed this question, submitting ELA2KO and wild-type (WT) mice to several models sensitive to anxiety- and depression-like, memory, and repetitive behaviors. Our data indicates a higher incidence of barbering behavior in ELA2KO compared to WT, as well as an anxiogenic phenotype, evaluated in the elevated plus maze (EPM). While a decrease in locomotor activity was observed in ELA2KO in EPM, this feature was not the main source of variation in the other parameters analyzed. The marble-burying test (MBT) indicated increase in repetitive behavior, observed by a higher number of buried marbles. The actimeter test indicated a decrease in total activity and confirmed the increase in repetitive behavior. The spatial memory was tested by repeated exposure to the actimeter in a 24-h interval. Both ELA2KO and WT exhibited decreased activity compared to the first exposure, without any distinction between the genotypes. However, when submitted to the cued fear conditioning, ELA2KO displayed lower levels of freezing behavior in the extinction session when compared to WT, but no difference was observed during the conditioning phase. Increased levels of BDNF were found in the prefrontal cortex but not in the hippocampus of ELA2KO mice compared to WT. Finally, in silico analysis indicates that ELA2 is putatively able to cleave BDNF, and incubation of the purified enzyme with BDNF led to the degradation of the latter. Our data suggested an anxiogenic- and antidepressant-like phenotype of ELA2KO, possibly associated with increased levels of BDNF in the prefrontal cortex.Peer reviewe

СОВРЕМЕННЫЕ ИННОВАЦИОННЫЕ ТЕХНОЛОГИИ ХРАНЕНИЯ СВЕЖИХ ФРУКТОВ И ОВОЩЕЙ И ПРОДУКТОВ ИХ ПЕРЕРАБОТКИ (ОБЗОР)

The article analyzes modern technologies for storing fruit and vegetable products and presents possible options for their modernization. From this perspective, the improvement of canning technology using non-traditional methods of processing plant raw materials is an urgent task, the solution of which will allow preserving fruit and vegetable products, reduce the amount of waste and reduce the impact of vegetable processing plants on natural water bodies. Fruits and vegetables are perishable products and require special storage conditions from the moment they are available for sale to purchase by consumers. Keeping them fresh for as long as possible is quite a challenge, as some plants are able to continue maturing even after packaging and produce ethylene, which initiates certain changes in texture and color, tissue degradation. The authors pay special attention to the aspects of innovative technologies in the creation of edible films and coatings, which are currently the only type of biodegradable polymer packaging that does not require individual collection and special conditions of disposal. This is their main difference from traditional biodegradable plastics, which were originally proposed as an alternative to synthetic polymeric materials, and all were convinced that their creation once and for all will solve the problem of waste polymer packaging, which today threatens to become a global environmental disaster. At the same time, they are always more expensive than conventional plastics, in many cases can not be subjected to joint recycling; being in the deep layers of the landfill, they emit greenhouse gas methane. In addition, the raw materials for biodegradable plastics are provided by the same soil and water resources on which food is grown today (except for a very small amount of plastics produced from agricultural waste), and therefore their raw material base will always be limited. Recommendations are formulated on the organization of effective conservation of plant raw materials, intended for further processing or sale in retail and wholesale trade networks.Рассмотрены современные технологии хранения продукции из фруктов и овощей и приведены возможные варианты их модернизации. Совершенствование технологии консервирования с использованием нетрадиционных способов обработки растительного сырья является актуальной задачей, решение которой позволит сохранить плодоовощную продукцию, уменьшить количество отходов и снизить воздействие овощеперерабатывающих предприятий на природные водные объекты. Фрукты и овощи являются скоропортящимися продуктами и требуют особых условий хранения с момента их поступления в продажу до покупки потребителями. Сохранение их свежести как можно дольше является достаточно сложной задачей, так как некоторые растения способны продолжать созревание даже после упаковки и вырабатывать этилен, который инициирует определенные изменения текстуры и цвета, деградацию тканей. Уделено внимание инновационным технологиям – созданию съедобных пленок и покрытий, являющихся в настоящее время единственным видом биоразлагаемой полимерной упаковки, которая не нуждается в индивидуальном сборе и особых условиях утилизации. Это их главное отличие от традиционных биоразлагаемых пластиков, которые первоначально были предложены как альтернатива синтетическим полимерным материалам. Преимущества биоразлагаемых пластиков проявляются только при их правильном сборе, т.е. отдельно от других отходов, и утилизации в специально созданных условиях, например, на компостных фабриках; при этом они дороже обычных пластиков, во многих случаях не могут быть подвергнуты совместному рециклингу; находясь в глубоких слоях свалки, выделяют парниковый газ метан. Кроме того, сырье для биоразлагаемых пластиков обеспечивают те же почвенные и водные ресурсы, на которых сегодня выращиваются продукты питания (кроме очень небольшого количества пластиков, производимых из отходов сельскохозяйственной продукции), а значит их сырьевая база всегда будет ограничена. Предложены рекомендации по организации эффективного сохранения растительного сырья, предназначенного для дальнейшей переработки или продажи в сетях розничной и оптовой торговли

РОЛЬ ЭНТЕРОВИРУСА ECHO 30 В ЭТИОЛОГИИ ЭНТЕРОВИРУСНОЙ ИНФЕКЦИИ НА СЕВЕРО -ЗАПАДЕ РОССИИ В 2013 г

In 2013 after two previous years when the situation had been calm the incidence rates of enterovirus infection significantly increased on certain territories of the North-West of Russia. In Novgorod and Vologda regions and in Saint-Petersburg enterovirus meningitis group cases were registered. The etiology of enterovirus infection was studied by virological and molecular methods. Enterovirus ECHO30 was identified as the principal etiological agent of the cases. Molecular study revealed that enteroviruses ECHO30 isolated in the North-West of Russia belonged to the genotype H and formed two subtypes inside this genotype. Phylogenetic analysis has shown that enteroviruses ECHO30 of both subtypes were closely related to the strains detected in different provinces of China in 2010-2013. Probably enteroviruses ECHO30 of the genotype H which largely circulated in Russia in 2013 and practically had not been detected in the country earlier had been imported on the territory of Russia from South-East Asia. Enteroviruses ECHO30 isolated in  Arkhangelsk and Novgorod regions in 2008-2009 belonged to another genotype Ec2. Enteroviruses of this genotype had circulated at that time in the European countries.В 2013 г. после относительно спокойной ситуации в течение двух предыдущих лет заболеваемость энтеровирусной инфекцией на ряде территорий Северо-Западного федерального округа резко возросла. Были зарегистрированы групповые заболевания энтеровирусным менингитом в Новгородской, Вологодской областях и в Санкт-Петербурге. Проведена расшифровка этиологии заболеваний энтеровирусной инфекцией с использованием вирусологического и молекулярно- генетического методов исследования. В качестве основного этиологического агента был идентифицирован энтеровирус ЕСНО 30. Установлено, что изолированные на Северо-Западе России вирусы ЕСНО 30 относились к генотипу Н и сформировали две филогенетические группы. Филогенетический анализ показал, что энтеровирусы ЕСНО 30 обоих субтипов были наиболее близко родственны штаммам, выделенным в разных провинциях Китая в 2010–2013 гг. Вероятно, энтеровирусы ЕСНО 30 генотипа Н, которые широко циркулировали в России в 2013 г. и ранее практически не выявлялись в стране, были импортированы на территорию России из Юго-Восточной Азии. Энтеровирусы ЕСНО 30, изолированные в 2008–2009 гг. в Архангельской и Новгородской областях, относились к другому генотипу Ес2, энтеровирусы этого генотипа циркулировали в тот период в странах Европы

HER-2/neu gene amplification in esophageal adenocarcinoma and its influence on survival

The original publication is available at the Annals website at www.springerlink.com/content/1534-4681.Background: HER-2/neu (c-erbB-2, HER2) gene amplification and protein overexpression have been associated with poor prognosis in several solid tumors, including breast and gastric cancer. Its incidence and significance in esophageal adenocarcinoma is unknown. Materials and Methods: Tissue microarrays were successfully constructed from 89 paraffin-embedded archival specimens of esophageal adenocarcinomas for HER2 gene amplification by silver-enhanced in situ hybridization (SISH). No patients had undergone neoadjuvant therapy. Protein overexpression was tested with immunohistochemistry (IHC) using automated immunostaining (Ventana Benchmark). Incidence of HER2 positivity, correlation to clinicopathological variables in esophageal cancer patients, and concordance between SISH and IHC were determined. Results: True HER2 gene amplification was detected in 14 esophageal cancer specimens (16%), and 92% of those with high-level HER2 amplification showed positive HER2 protein overexpression. No significant associations were found among gene amplification and clinicopathological factors. The 5-year survival rates were 57% for esophageal cancer patients with HER2 amplification compared with 32% without, but the difference in overall survival was not significant (P = .37). The correlation between SISH and IHC was statistically significant (P < .0001). Conclusion: While molecular targeting may be possible for approximately 16% of esophageal adenocarcinoma patients, HER2 oncogene amplification did not influence survival in this study.Sarah K. Thompson, Thomas R. Sullivan, Ruth Davies and Andrew R. Ruszkiewic

Frequent HPV-independent p16/INK4A overexpression in head and neck cancer

Objectives p16INK4A (p16) is the most widely used clinical biomarker for Human Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a favourable prognostic marker in HNSCC and is used for patient stratification. While p16 is a relatively accurate marker for HPV within the oropharynx, recent reports suggest it may be unsuitable for use in other HNSCC subsites, where a smaller proportion of tumors are HPV-driven. Materials and methods We integrated reverse phase protein array (RPPA) data for p16 with HPV status based on detection of viral transcripts by RNA-seq in a set of 210 HNSCCs profiled by The Cancer Genome Atlas project. Samples were queried for alterations in CDKN2A, and other pathway genes to investigate possible drivers of p16 expression. Results While p16 levels as measured by RPPA were significantly different by HPV status, there were multiple HPV (?) samples with similar expression levels of p16 to HPV (+) samples, particularly at non-oropharyngeal subsites. In many cases, p16 overexpression in HPV (?) tumors could not be explained by mutation or amplification of CDKN2A or by RB1 mutation. Instead, we observed enrichment for inactivating mutations in the histone H3 lysine 36 methyltransferase, NSD1 in HPV (?)/p16-high tumors. Conclusions RPPA data suggest high p16 protein expression in many HPV (?) non-oropharyngeal HNSCCs, limiting its potential utility as an HPV biomarker outside of the oropharynx. HPV-independent overexpression of wild-type p16 in non-oropharyngeal HNSCC may be linked to global deregulation of chromatin state by inactivating mutations in NSD1

Analysis of the Polymer Two-Layer Protective Coating Impact on Panda-Type Optical Fiber under Bending

The article discusses the effects of thermal-force on the Panda-type optical fiber. The studies used a wide temperature range. The research used two thermal cycles with exposures to temperatures of 23, 60 and −60 °C. The field of residual stresses in the fiber formed during the drawing process was determined and applied. Panda was considered taking into account a two-layer viscoelastic polymer coating under conditions of tension winding on an aluminum coil in the framework of a contact problem. The paper investigated three variants of coil radius to analyze the effect of bending on fiber behavior. The effect of the coating thickness ratio on the system deformation and optical characteristics was analyzed. Qualitative and quantitative patterns of the effect of temperature, bending, thickness of individual polymer coating layers and relaxation transitions of their materials on the Panda optical fiber deformation and optical characteristics were established. Assessment of approaches to the calculation of optical characteristics (values of the refractive indices and fiber birefringence) are given in the framework of the study. The patterns of deformation and optical behavior of the Panda-type fiber with a protective coating, taking into account the nonlinear behavior of the system materials, were original results

Non-classical effects of sildenafil in clinical medicine: an interdisciplinary approach

Based on the results of modern clinical and experimental studies, the review article discusses issues of pharmacotherapeutic feasibility, pathogenetic validity and safety of the first and most studied phosphodiesterase type 5 inhibitor – sildenafil – in general clinical practice according to «non-classical» (non-erectogenic) indications in the framework of an interdisciplinary approach modern medicine. As it is known, at present, phosphodiesterase type 5 inhibitors are both the «first line» therapy for treating erectile dysfunction (as monotherapy), as well as an effective option for monotherapy or combined pharmacotherapy of lower urinary tract symptoms on the background of benign prostatic hyperplasia in men with erectile dysfunction. However, given the universality and fundamentality of the mechanisms of their pharmacological action (first of all, the effect on the metabolism of one of the key vasomodulators of the vascular bed, nitric oxide NO), the list of potential and promising indications for prescribing these drugs is constantly expanding due to the presence of various «non-classical» (non-erectogenic) effects, which makes them very attractive for wider application not only in urological practice, but also in other medical specialties. The article describes in more detail and purposefully the accumulated to date scientific and practical data on the effectiveness of the use and potential mechanisms of action of sildenafil in cardiology, endocrinology, neurology, nephrology, obstetrics and gynecology, andrological reproductology and oncology, and also presents the results of studies confirming its safety in the treatment of relevant specialized diseases