61 research outputs found

    Loss of Sialic Acid Binding Domain Redirects Protein σ1 to Enhance M Cell-Directed Vaccination

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    Ovalbumin (OVA) genetically fused to protein sigma 1 (pσ1) results in tolerance to both OVA and pσ1. Pσ1 binds in a multi-step fashion, involving both protein- and carbohydrate-based receptors. To assess the relative pσ1 components responsible for inducing tolerance and the importance of its sialic binding domain (SABD) for immunization, modified OVA-pσ1, termed OVA-pσ1(short), was deleted of its SABD, but with its M cell targeting moiety intact, and was found to be immunostimulatory and enhanced CD4+ and CD8+ T cell proliferation. When used to nasally immunize mice given with and without cholera toxin (CT) adjuvant, elevated SIgA and serum IgG responses were induced, and OVA-pσ1(s) was more efficient for immunization than native OVA+CT. The immune antibodies (Abs) were derived from elevated Ab-forming cells in the upper respiratory tissues and submaxillary glands and were supported by mixed Th cell responses. Thus, these studies show that pσ1(s) can be fused to vaccines to effectively elicit improved SIgA responses

    Флуоресцентная диагностика с хлорином е6 в хирургии глиом низкой степени злокачественности

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    Intraoperative fluorescence diagnostics of high-grade gliomas is widely used in neurosurgical practice. This work analyzes the possibilities of fluorescence diagnostics for low-grade gliomas (LGG) using chlorin e6 photosensitizer. The study included patients with newly diagnosed LGG, for whom chlorin e6 was used for intraoperative fluorescence control at a dose of 1 mg/kg. During the operation, the fluorescence intensity of various areas of the putative tumor tissue was analyzed using the RSS Cam – Endo 1.4.313 software. Tissue samples with various degrees of fluorescence intensity were compared with the results of their histopathological analysis (WHO tumor diagnosis, Ki-67 index, P53, VEGF). Fluorescence was detected in more than half of the cases, but in most cases had a focal character and low fluorescence intensity. The fluorescence intensity directly correlated with the data of histopathological examination of tumor tissues (Ki-67 index (p=0.002), expression of P53 (p=0.0015) and VEGF (p=0.001)). The sensitivity of the method for LGG surgery was 72%, the specificity was 56,7%. Intraoperative fluorescence diagnostics with chlorin e6 can be used in LGG surgery, especially to visualize intratumoral areas with a higher degree of anaplasia.Применение интраоперационной флуоресцентной диагностики для глиом высокой степени злокачественности широко используется в нейрохирургической практике. В работе проанализированы возможности флуоресцентной диагностики для глиом низкой степени злокачественности с использованием хлорина е6. В исследование были включены пациенты с впервые диагностированной глиомой низкой степени злокачественности (low-grade glioma, LGG), у которых с целью интраоперационного флуоресцентного контроля применен препарат хлорин е6 в дозе 1 мг/кг массы тела. В процессе операции анализировали интенсивность флуоресценции различных участков предполагаемой опухолевой ткани с использованием программного обеспечения RSS Cam – Endo 1.4.313. Образцы тканей различной степени интенсивности флуоресценции сопоставляли с результатами их гистопатологического анализа (диагностика опухоли ВОЗ, индекс Ki-67, P53, VEGF). Флуоресценция выявлена в более чем половине случаев, но в большинстве случаев имела очаговый характер и низкую интенсивность флуоресценции. Интенсивность флуоресценции напрямую коррелировала с данными гистопатологического исследования тканей опухоли: индекс Ki-67 (p=0,002), экспрессия P53 (p=0,0015), VEGF (p=0,001). Чувствительность метода для хирургии LGG составила 72%, специфичность 56,7%. Проведенное исследование подтвердило, что технология интраоперационной флуоресцентной диагностики с применением хлорина е6 может применяться в хирургии LGG, особенно для визуализации внутриопухолевых участков с более высокой степенью анаплазии

    Multiple Myeloma with Intracranial Distribution

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    Multiple myeloma (MM) is a malignant immunoproliferative disease involving plasma cells, leading to their malignant proliferation and the production of monoclonal paraproteins. Intracranial tumor spread in MM is very rare. This is a unique and infrequent localization, which makes it difficult to diagnose the disease. We report a rare case of treatment of a patient with MM intracranial spread, whose disease was presumably in remission and recurred as an intracranial plasmacytoma with a clinical picture of acute cerebrovascular accident. Surgical intervention was performed to remove the tumor, a histopathological analysis of the removed tissue was carried out. Even with early diagnosis, the prognosis remains bleak, with median survival rates of 3 to 6 months. However, aggressive multimodal treatment can prolong life by months

    Summertime Influence of Asian Pollution in the Free Troposphere over North America

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    We analyze aircraft observations obtained during INTEX-A (1 July 14 - August 2004) to examine the summertime influence of Asian pollution in the free troposphere over North America. By applying correlation analysis and Principal Component Analysis (PCA) to the observations between 6-12 km, we find dominant influences from recent convection and lightning (13 percent of observations), Asia (7 percent), the lower stratosphere (7 percent), and boreal forest fires (2 percent), with the remaining 71 percent assigned to background. Asian airmasses are marked by high levels of CO, O3, HCN, PAN, acetylene, benzene, methanol, and SO4(2-). The partitioning of reactive nitrogen species in the Asian plumes is dominated by peroxyacetyl nitrate (PAN) (approximately 600 pptv), with varying NO(x)/HNO3 ratios in individual plumes consistent with different plumes ages ranging from 3 to 9 days. Export of Asian pollution in warm conveyor belts of mid-latitude cyclones, deep convection, and lifting in typhoons all contributed to the five major Asian pollution plumes. Compared to past measurement campaigns of Asian outflow during spring, INTEX-A observations display unique characteristics: lower levels of anthropogenic pollutants (CO, propane, ethane, benzene) due to their shorter summer lifetimes; higher levels of biogenic tracers (methanol and acetone) because of a more active biosphere; as well as higher levels of PAN, NO(x), HNO3, and O3 (more active photochemistry possibly enhanced by injection of lightning NO(x)). The high delta O3/delta CO ratio (0.76 mol mol(exp -1)) of Asian plumes during INTEX-A is due to a combination of strong photochemical production and mixing with stratospheric air along isentropic surfaces. The GEOS-Chem global chemical transport model captures the timing and location of the Asian plumes remarkably well. However, it significantly underestimates the magnitude of the enhancements

    Фотодинамическая терапия в нейроонкологии

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    Literature review reflects the current status and development status of intraoperative photodynamic therapy in neurooncology and discusses the results of the most important studies on photodynamic  therapy (PDT). We searched the Pubmed, EMBASE, Cochrane Library and eLibrary data-bases for publications  published  between January 2000 and December 2022. Found 204 publications  in foreign sources and 59 publications  in domestic editions, dealing with the issues of photodynamic  therapy in neurooncology. An analysis of the literature has shown that intraoperative PDT in neurooncology is an important tool that contributes to increasing the radicality of the operation and local control. The basic rationale for the effectiveness of PDT lies in the study of the pathways leading to the complete devitalization of a malignant tumor, the study of the mechanisms of the local and systemic immune response. In addition, subcellular targets in PDT are determined by the properties of photosensitizers (PS). Second generation PSs have already been introduced into clinical practice. The effectiveness of PDT using photoditazine, 5-aminolevulinic acid has been demonstrated. The mechanisms of action and targets of these PS have been established. In Russia, a number of studies have repeatedly shown and proved the clinical effectiveness of PDT in groups of neurooncological patients with glial tumors and secondary metastatic tumors, but so far, the method has not been included in the clinical guidelines for the provision of high-tech neurosurgical care. There is certainly a need for further development of PTD techniques in neurooncology, especially in patients at high risk of recurrence and aggressive CNS tumors.Выполнен обзор литературы, отражающий современное состояние и степень разработанности  методики интраоперационной  фотодинамической терапии (ФДТ) в нейроонкологи. Представлены к обсуждению результаты наиболее значимых исследований, посвященных ФДТ в нейроонкологии. Проведен анализ научных публикаций по данной тематике в базах данных Pubmed, EMBASE, Cochrane Library и eLibrary, опубликованных в промежуток времени с января 2000 г. по декабрь 2022 г. Найдено 204 публикации в зарубежных источниках  и 59 публикаций в отечественных  изданиях, в которых рассматриваются  вопросы применения ФДТ в нейроонкологии. Анализ литературы показал, что в клинической практике интраоперационная  ФДТ в нейроонкологии  является важным инструментом, способствующим увеличению радикальности операции и локального контроля. Фундаментальное обоснование эффективности ФДТ заключается в изучении путей, ведущих к полной девитализации злокачественной  опухоли, изучении механизмов локального и системного  иммунного ответа. При этом субклеточные  мишени при ФДТ обусловлены свойствами  фотосенсибилизаторов (ФС). В многочисленных  исследованиях  показана противоопухолевая эффективность  использования  ФДТ с ФС на основе  хлорина  е6, 5-аминолевулиновой  кислоты, производных  порфиринов.  Установлены механизмы действия и мишени этих ФС. В России  в ряде исследований подтверждена клиническая эффективность  ФДТ у групп нейроонкологических пациентов с глиальным опухолями и вторичными метастатическими опухолями, однако до сих пор метод не включён в клинические рекомендации по оказанию высокотехнологичной  нейрохирургической помощи. Безусловно, необходима дальнейшая разработка методики ФДТ в нейроонкологии, особенно у пациентов с высоким риском рецидива и агрессивными опухолями ЦНС
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