231 research outputs found

    О двух сущностях человека. „Задумчивый странник” Зи- наидыГиппиус

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    The article is an attempt to describe the conception of androgyny in ZinaidaGippius’s work entitled Reflective wanderer. The main character of Reflective wandereris a modernistic philosopher, Vasily Rozanov. The aim of this article is to analyse the image of Rozanov and prove that he is an example of androgynous man being.The article is an attempt to describe the conception of androgyny in ZinaidaGippius’s work entitled Reflective wanderer. The main character of Reflective wandereris a modernistic philosopher, Vasily Rozanov. The aim of this article is to analyse the image of Rozanov and prove that he is an example of androgynous man being

    Effector mechanisms of anti-CD20 monoclonal antibodies in B cell malignancies.

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    Activation of the complement system by tumor cells was long believed to only benefit the host. Overexpression of complement inhibitors by many tumor cell types and results obtained in several experimental animal models were all in agreement with this hypothesis. However, recent reports imply that the situation is more complex than initially believed and that under certain circumstances tumor cells may use complement to their own advantage, e.g. by recruitment of suppressor T cells or promoting local angiogenesis. Such a dual role of complement may also be apparent when considering the effect of therapeutic monoclonal antibodies (mAb) used to successfully treat B cell malignancies, such as CD20 mAbs. Some argue that besides direct tumor cell killing by mAbs, two main immune effector mechanisms, complement dependent cytotoxicity (CDC) and antibody dependent cellular cytotoxicity (ADCC), may be competing with each other. Experiments aiming at answering the question whether complement is our friend or foe in mAb therapy ended up with seemingly contradictory conclusions. Herein, we revisit the existing knowledge on this pivotal issue based on rituximab and other anti-CD20 mAb as a model of therapeutic agents

    Jakość życia pacjentów ze schizofrenią

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    Introduction. Schizophrenia is a mental illness characterized by a varied picture and clinical course, characterized primarily by disturbances in thinking and perception, as well as maladjusted and shallow affect. The etiopathogenesis is not fully known, one of the accepted theories is the involvement of biopsychosocial factors, including stress. The age of onset usually falls in early adulthood - for women it is 25–34 years of age, and for men 15–24 years of age. The aim. The aim of the research was to assess the quality of life in the context of the life domains of patients with schizophrenia. Materials and methods. The study included a group of 100 patients treated at Szpital Lipno Sp. z o.o. who have been diagnosed with schizophrenia. The age of the respondents ranged from 18–75 years. The research tool was the SQLS-R4 questionnaire (Schizophrenia Quality of Life Scale Revision 4) extended with an original certificate. Results. The respondents, making a subjective assessment of the quality of life, described it as satisfactory. The quality of life in the vital sphere was higher than in the psychosocial domain and in general satisfaction Conclusions. Schizophrenia is a disease that significantly contributes to the reduction of the quality of life, mainly in the psychosocial domainWstęp. Schizofrenia jest chorobą psychiczną, którą charakteryzuje zróżnicowany obraz i przebieg kliniczny, charakteryzuje się przede wszystkim zakłóceniami myślenia i postrzegania, a także niedostosowanym i spłyconym afektem. Etiopatogeneza nie jest do końca znana, jedną z uznawanych teorii jest udział czynników biopsychospołecznych, w tym stresu. Wiek zachorowania przypada zazwyczaj na okres wczesnej dorosłości – u kobiet jest to 25–34 rok życia, a u mężczyzn 15 –24 rok życia. Cel. Celem badań była ocena jakości życia w kontekście domen życia pacjentów ze schizofrenią. Materiały i metody. Badaniem objęto grupę 100 pacjentów leczonych w Szpital Lipno Sp. z o.o. , u których zdiagnozowano schizofrenię. Wiek badanych mieścił się w zakresie  18–75 lat. Narzędziem badawczym był kwestionariusz SQLS-R4 (Schizophrenia Quality of Life Scale Revision 4) poszerzony o autorską metryczkę. Wyniki. Respondenci dokonując subiektywnej oceny  jakości życia określili jako stan zadawalający. Jakość życia w sferze witalnej była na wyższym poziomie niż w domenie psychospołecznej oraz ogólnym zadowoleniu. Wnioski. Schizofrenia to schorzenia, które w istotny sposób przyczynia się do obniżenia poziomu jakości życia głównie w domenie psychospołecznej

    Killing of CLL and NHL cells by rituximab and ofatumumab under limited availability of complement.

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    Rituximab and ofatumumab are anti-CD20 antibodies applicable to treatment for non-Hodgkin's lymphoma and chronic lymphocytic leukemia (CLL). Effectiveness of both immunotherapeutics may depend on exhaustible complement system. To model the efficacy of complement usage by ofatumumab and rituximab under limited complement availability, we compared complement-dependent cytotoxicity exerted by these antibodies at low (5 and 10 %) and physiological (50 %) serum concentration in twelve CD20-positive cell lines and six freshly isolated CLL cells. Simultaneously, we assessed the expression of CD20 and membrane-bound complement inhibitors. Ratios of CD20 to CD59 and/or CD55 distinguished highly sensitive cells lysed equally efficient by both antibodies from the moderately sensitive cells, which were killed more efficiently by ofatumumab

    Heavy chains of inter alpha inhibitor (IαI) inhibit the human complement system at early stages of the cascade .

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    Inter alpha inhibitor (IαI) is an abundant serum protein consisting of three polypeptides: two heavy chains (HC1 and HC2) and bikunin, a broad-specificity Kunitz-type proteinase inhibitor. The complex is covalently held together by chondroitin sulphate but during inflammation IαI may interact with TNF-stimulated gene 6 protein (TSG-6), which supports transesterification of heavy chains to hyaluronan. Recently, IαI was shown to inhibit mouse complement in vivo and to protect from complement-mediated lung injury but the mechanism of such activity was not elucidated. Using human serum depleted from IαI, we found that IαI is not an essential human complement inhibitor as reported for mice and that such serum has unaltered hemolytic activity. However, purified human IαI inhibited classical, lectin and alternative complement pathways in vitro when added in excess to human serum. The inhibitory activity was dependent on heavy chains but not bikunin and detected at the level of initiating molecules (MBL, properdin) in the lectin/ alternative pathways or C4b in the classical pathway. Furthermore, IαI affected formation and assembly of C1 complex and prevented assembly of the classical pathway C3-convertase. Presence and putative interactions with TSG-6 did not affect the ability of IαI to inhibit complement thus implicating IαI as a potentially important complement inhibitor once enriched onto hyaluronan moieties in the course of local inflammatory processes. In support of this, we found a correlation between IαI/HC-containing proteins and hemolytic activity of synovial fluid from patients suffering from rheumatoid arthritis

    Complement inhibitor CSMD1 acts as tumor suppressor in human breast cancer

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    Human CUB and Sushi multiple domains 1 (CSMD1) is a membrane-bound complement inhibitor suggested to act as a putative tumor suppressor gene, since allelic loss of this region encompassing 8p23 including CSMD1 characterizes various malignancies. Here, we assessed the role of CSMD1 as a tumor suppressor gene in the development of breast cancer in vitro and in vivo. We found that human breast tumor tissues expressed CSMD1 at lower levels compared to that in normal mammary tissues. The decreased expression of CSMD1 was linked to a shorter overall survival of breast cancer patients. We also revealed that expression of CSMD1 in human breast cancer cells BT-20 and MDA-MB-231 significantly inhibited their malignant phenotypes, including migration, adhesion and invasion. Conversely, stable silencing of CSMD1 expression in T47D cells enhanced cancer cell migratory, adherent and clonogenic abilities. Moreover, expression of CSMD1 in the highly invasive MDA-MB-231 cells diminished their signaling potential as well as their stem cell-like properties as assessed by measurement of aldehyde dehydrogenase activity. In a xenograft model, expression of CSMD1 blocked the ability of cancer cells to metastasize to secondary sites in vivo, likely via inhibiting local invasion but not the extravasation into distant tissues. Taken together, these findings demonstrate the role of CSMD1 as a tumor suppressor gene in breast cancer
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