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Leung, Janet T. Y., Daniel T. L. Shek i Cecilia M. S. Ma. "Measuring Perceived Parental Sacrifice Among Adolescents in Hong Kong: Confirmatory Factor Analyses of the Chinese Parental Sacrifice Scale". Child Indicators Research 9, nr 1 (29.03.2015): 173–92. http://dx.doi.org/10.1007/s12187-015-9313-7.
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Sorokoumova, E., E. Mamonova, O. Suvorova i S. Sorokoumova. "Peculiarities of parental attitudes of young mothers with various parental experience". Pedagogy and Psychology of Education, nr 3, 2019 (2019): 152–66. http://dx.doi.org/10.31862/2500-297x-2019-3-152-166.
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The concepts of motherhood and parenthood are considered from the point of view of parental functions. A study was conducted of the parental attitudes of young mothers aged 20 to 35 y.o., who have the only child or a second child not older than 3. Among the 60 participants surveyed: 30 young mothers with one child and 30 mothers with parenting experience. The results of the study showed that the experience of parenting affects the attitude to family roles and to the child. The analysis of the results of the study of parental attitudes made it possible to record a significant number of significant differences (“attitude to family roles” – t = 2.46; р = 0.003; “restriction to the role of a housewife” – t = 4.07; р = 0.04; “sacrifice of parents” – t = 3.81; р = 0.05; “emotional distance with the child” – t = 3.66; р = 0.03; “excessive concentration on the child” – t = 4.58; р = 0.05; “contact” – t = 2.62; р = 0.005; “cognitive needs” – t = 3.97; р = 0.001; “creativity” – t = 3.51; р = 0.0001). Young mothers with one child limit their interests to the family, which creates a sense of sacrifice and provokes family conflicts; with a child, such a mother is emotionally close and encourages their activity. Experienced mothers do not limit their interests to family boundaries, while being satisfied with family relationships, the attitude towards the child is more authoritarian, such mothers are not emotionally close to the child and are strict. That is, the experience of parenting has a mixed effect on parental attitudes. In the group of young mothers with one child, it is necessary to get rid of the feeling of self-sacrifice in the family, increase self-esteem, and also reduce excessive care for the child. In a group of young mothers with parenting experience, it is necessary to reduce the authoritarian influence on the child, irritability and severity.
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Ceballo, Rosario, Laura K. Maurizi, Gloria A. Suarez i Maria T. Aretakis. "Gift and sacrifice: Parental involvement in Latino adolescents’ education." Cultural Diversity and Ethnic Minority Psychology 20, nr 1 (2014): 116–27. http://dx.doi.org/10.1037/a0033472.
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McConnell, Sean. "Lucretius on the Nature of Parental Love". Antichthon 52 (2018): 72–89. http://dx.doi.org/10.1017/ann.2018.1.
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AbstractThis paper outlines the full details of Lucretius’ treatment of parental love. It shows that Lucretius is faithful to Epicurus’ notorious claim that parental love is not natural: in addition to orthodox Epicurean hedonist concerns, Lucretius asserts that children do not ‘belong to’ their parents by nature; as such, even though parental love is now ubiquitous and indeed a cultural norm, there is no basis for the naturalness of parental love. This model of the relationship between parents and children does not, however, apply in the case of certain animals, who do have natural parental love for their offspring. Focussing on two famous scenes, the sacrifice of Iphigenia and the forlorn heifer seeking her sacrificed calf, the paper argues that, by highlighting the fragility of human parental love in comparison to that of the animals, Lucretius brings to his Roman readers’ attention the relative weakness of the familial ties that bond human beings together. At the same time, he emphasises the need to maintain these ties, if social and political concord, with all its benefits, is to continue. It transpires that unlocking the details of Lucretius’ treatment of parental love brings a key lesson of the poem into clearer focus.
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Leung, J. T. Y., i D. T. L. Shek. "Parental Beliefs and Parental Sacrifice of Chinese Parents Experiencing Economic Disadvantage in Hong Kong: Implications for Social Work". British Journal of Social Work 45, nr 4 (26.11.2013): 1119–36. http://dx.doi.org/10.1093/bjsw/bct190.
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Leung, Janet T. Y., i Daniel T. L. Shek. "Parental Sacrifice, Filial Piety and Adolescent Life Satisfaction in Chinese Families Experiencing Economic Disadvantage". Applied Research in Quality of Life 15, nr 1 (17.11.2018): 259–72. http://dx.doi.org/10.1007/s11482-018-9678-0.
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Leung, Janet T. Y. "Parent-Adolescent Discrepancies in Perceived Parental Sacrifice and Adolescent Developmental Outcomes in Poor Chinese Families". Journal of Research on Adolescence 28, nr 2 (16.10.2017): 520–36. http://dx.doi.org/10.1111/jora.12356.
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Leung, Janet T. Y. "Perceived parental sacrifice, filial piety and hopelessness among Chinese adolescents: A cross-lagged panel study". Journal of Adolescence 81 (czerwiec 2020): 39–51. http://dx.doi.org/10.1016/j.adolescence.2020.04.005.
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Leung, Janet T. Y., i Daniel T. L. Shek. "Parent–Child Discrepancies in Perceived Parental Sacrifice and Achievement Motivation of Chinese Adolescents Experiencing Economic Disadvantage". Child Indicators Research 9, nr 3 (5.09.2015): 683–700. http://dx.doi.org/10.1007/s12187-015-9332-4.
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Svynarenko, Radion. "ATTITUDES TOWARD PARENTAL FINANCIAL SUPPORT OF YOUNG-ADULT CHILDREN". Innovation in Aging 3, Supplement_1 (listopad 2019): S673. http://dx.doi.org/10.1093/geroni/igz038.2489.
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Abstract Studies have shown that Americans do not save enough for retirement because they prioritize providing support of their young-adult children over saving for retirement. Attitudes toward parental support has been largely overlooked in existing literature. Using a factorial vignette experimental design and a sample of 500 Americans of age 40 and older, this study investigated how manipulation of contextual factors changed endorsement of parental support. This study found that endorsement of parental support varied depending on the goal of support, whether it was to purchase a car, pay for school tuition, or to pay for down payment for a house. Thus, 67% of respondents endorsed parental financial assistance with purchasing a car, 44% endorsed down payment for a house, and only 38% endorsed paying for college tuition, reflecting overall social importance of these three elements in becoming an adult person. Gender of the child did not affect endorsement of parental financial support to adult children, indicating that there were no gender specific social expectations of who should receive more support from parents, daughters or sons. The major motives of parental support included (a) desire to be a “good parent” and to take responsibility for the child, (b) expectation that children would eventually pay back their parents, and (c) desire to make sacrifice for own children. Parental support may provide numerous benefits to both children and their parents; however, it is important to educate parents on ways to support their children without threatening their own financial needs in retirement.
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Andruko, J., i T. Green. "P138: Parental leave policies and culture for physicians in emergency medicine". CJEM 22, S1 (maj 2020): S114. http://dx.doi.org/10.1017/cem.2020.342.
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Introduction: Medicine demands a sacrifice of physicians’ personal life, but culture has slowly changed towards valuing a balanced work life. Parental leave is linked to better physical and mental health, but policies and culture surrounding parental leave are largely unstudied in the Canadian Emergency Medicine landscape. Anecdotally, experiences vary widely. This study was designed to determine what proportion of Canadian Emergency Departments have formal parental leave policies (maternity, paternity, and other ex. adoption) and what proportion of Canadian EM physicians are satisfied with their department's parental leave policies. Methods: Two surveys were generated; one to assess attitudes and experiences of emergency physicians, and a second survey for department chiefs assessed the policies and their features. These were approved by the UBC REB and distributed through the CAEP Research Committee. Primary outcomes were physician satisfaction with their department's parental leave policy (4-5/5 Likert Scale), and departments with a formal parental leave policy (Y/N). Results: 38% (8/21) of department chiefs reported having a formal policy for maternity leave, 29% (6/21) for paternity leave, and 24% (5/21) other. The survey of Emergency Physicians revealed similar rates at 48% (90/187) maternity, 40% (70/184) paternity, 29% (53/181) other. Among physicians who were aware of them, 69% (62/90) were somewhat or very satisfied with the maternity leave policies, 58% (51/88) with paternity leave policies, and 48% (39/81) with other parental leave. Less than 10% were somewhat or very dissatisfied with any of these. Several department chiefs commented that they had never refused anyone parental leave, but have no formal policy. However, 87% (147/187) of physicians reported a formal maternity leave policy was somewhat or very important to them; similarly 80% (134/187) paternity leave. Less than 15% felt each was somewhat or extremely unimportant. Conclusion: Presence and type of parental leave policy varies across the country. Most physicians were satisfied with the support they had available, but the vast majority felt that a formal maternity and paternity leave policy itself was important. This study would suggest that, without actually changing practice, the introduction of a formal parental leave policy is of value. Our research group will use this data to collaborate on a template parental leave policy to be made available for this purpose.
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Bettella, Patrizia. "Vicarious Mothers in Fascist Regime Cinema". Mnemosyne, nr 8 (15.10.2018): 24. http://dx.doi.org/10.14428/mnemosyne.v0i8.13923.
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Fascist regime proclaimed that women’s preeminent roles were those of wife, mother and breeder of many children fot the Fatherland. The myth of motherhood became central in Fascism. Yet a limited number of documentaries and commercial films deals with motherhood. In commercial films it is remarkable to find that some maternal melodramas focus on the vicarious mothers, a generous, self- sacrificing woman, who acts as the mother of a child who is not her own. The article examines Righelli’s La canzone dell’amore, Ballerini’s La fuggitiva and Poggioli’s Sissignora where the surrogate mother, a young orphans with no parental experience, is juxtaposed with the biological parent, who is portrayed as a bad mother. The self-centred, transgressive biological mother contrasts with the exemplary vicarious mother, who, like a Marian figure, is willing to sacrifice herself for the good of her putative child.
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Hotchkins, Bryan, i Jon McNaughtan. "Examining the continuum of Black student leadership: From community to college and beyond". education policy analysis archives 29 (29.03.2021): 42. http://dx.doi.org/10.14507/epaa.29.4695.
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This qualitative comparative case study examines the leadership involvement of 11 Black collegians and how they make sense of enacting transgenerationally informed knowledge(s) as racial socialization to navigate a predominantly White institution (PWI) campus. Findings indicated participants used elder communal instruction and parental home pedagogy to inform what it means to be leaders who enact social justice while Black. Emergent themes were: 1) Collective Definition; and 2) Self-sacrifice. Participants indicated parents and elders racially socialized them to be self-sacrificing leaders who used values, respect, and honor to preserve Black culture, people, and traditions. Racial socialization processes influenced students to become leaders who built and sustained Black college communities by being resilient. Participants acknowledged that although resiliency was important there was added value in practicing racial resistance, which allowed for exposing racially threatening oppositions and identify acts of racism that were menacing.
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Xia, Ying, Shanshan Zuo, Yanhua Zheng, Jin Liu, Wenxiang Yang, Xiaoqiao Tang, Xianghong Ke i in. "Subchronic Oral Toxicity Study of Genetically Modified Rice Rich in β-Carotene in Wistar Rats". International Journal of Environmental Research and Public Health 18, nr 11 (21.05.2021): 5526. http://dx.doi.org/10.3390/ijerph18115526.
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(1) Background: a hybrid black rice rich in β-carotene carrying the psy and crtI genes (HJM) was evaluated in Wistar rats by a 90-day feeding study, aiming to assess its dietary safety. (2) Methods: the HJM rice and its parental line HS were included in rats’ diets at levels of 73.5% and 75.5%, respectively. The AIN-93 diet was administered as a nutritional control. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. (3) Results: Some parameters were found to be significantly different, though they remained within the normal range for rats of this breed and age. In addition, upon sacrifice, various organs were weighed, and macroscopic and histopathological examinations were performed, with only minor changes to report. (4) Conclusions: HJM rice exhibited no adverse or toxic effects in Wistar rats in this 90-day study.
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Kaartinen, Miia, Kaija Puura, Päivi Pispa, Mika Helminen, Raili Salmelin, Erja Pelkonen, Petri Juujärvi, Esther B. Kessler i David H. Skuse. "Associations between cooperation, reactive aggression and social impairments among boys with autism spectrum disorder". Autism 23, nr 1 (10.11.2017): 154–66. http://dx.doi.org/10.1177/1362361317726417.
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Cooperation is a fundamental human ability that seems to be inversely related to aggressive behaviour in typical development. However, there is no knowledge whether similar association holds for children with autism spectrum disorder. A total of 27 boys with autism spectrum disorder and their gender, age and total score intelligence matched controls were studied in order to determine associations between cooperation, reactive aggression and autism spectrum disorder–related social impairments. The participants performed a modified version of the Prisoner’s Dilemma task and the Pulkkinen Aggression Machine which measure dimensions of trust, trustworthiness and self-sacrifice in predisposition to cooperate, and inhibition of reactive aggression in the absence and presence of situational cues, respectively. Autism spectrum disorder severity–related Autism Diagnostic Interview-algorithm scores were ascertained by interviewing the parents of the participants with a semi-structured parental interview (Developmental, Dimensional and Diagnostic Interview). The results showed that albeit the boys with autism spectrum disorder were able to engage in reciprocation and cooperation regardless of their social impairments, their cooperativeness was positively associated with lower levels of reactive aggression and older age. Thus, strengthening inhibition mechanisms that regulate reactive aggression might make boys with autism spectrum disorder more likely to prefer mutual gain over self-interest in cooperation.
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Plum, M. Colette. "Lost Childhoods in a New China: Child-Citizen-Workers at War, 1937–1945". European Journal of East Asian Studies 11, nr 2 (2012): 237–58. http://dx.doi.org/10.1163/15700615-20121106.
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This article examines the emerging discourse of child-citizen-workers in wartime China and demonstrates how this concept of children’s citizenship was put into practice in work training programs within wartime children’s homes. This article argues that the idea of child-citizen-workers grew from three pre-war antecedents that converged and were greatly accelerated by China’s war with Japan: the new idea of an autonomous sphere of childhood articulated during the early Republican period; a progressive education movement to introduce labor training and experiential learning as essential elements of modern education; and Nationalist state-building and activist efforts at family reform, which viewed traditional parents with distrust and increasingly intervened in family life. The second half of the article focuses particularly on orphans, who were considered potentially unstable social elements due to their position outside the control of families, and whose lack of parental protection made them available for appropriation. This article demonstrates that the war opened up a space in which Guomindang state-builders, working with educators and childcare workers, attempted to restructure orphans lives within wartime child welfare institutions to realize a vision for China’s future: the ideal of child-citizen-workers habituated toward sacrifice for the nation.
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Havrylkevych, Viacheslav, Larysa Podkorytova, Larysa Danylchuk, Liudmila Romanovska, Tetiana Kravchyna i Olena Chovgan. "Psychological Correction of Parents' Attitude to Their Children with Special Educational Needs by Means of Art Therapy". BRAIN. BROAD RESEARCH IN ARTIFICIAL INTELLIGENCE AND NEUROSCIENCE 12, nr 1 (29.03.2021): 154–71. http://dx.doi.org/10.18662/brain/12.1/176.
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The paper presents the results of empirical study of parents' attitudes towards their children with special educational needs. The following methods have been used: PARI method (E. Schaefer, R. Bell; adaptation by T. Nescheret), test-questionnaire of parental attitude of A. Varga and V. Stolin; questionnaire 'Analysis of family myth' by A. Nesterova. To clarify and deepen the analysis of research data, two samples of selected participants have been created: a) parents of children with special educational needs and b) parents of children without special educational needs. Two Google forms have been made with appropriate introductory questionnaires and research instructions. The analysis of the results obtained by the methods has revealed the following tendencies in the attitude of parents of children with special educational needs, in comparison with parents of other children: lower level of acceptance; greater concentration on the child and his/her control; a kind of inconsistency in the attitude to their children (simultaneous optimal emotional contact and excessive emotional distance); a sense of self-sacrifice and belief in its necessity. It has been proved, that the usage of different types and forms of art therapy (music, dance-movement, bibliotherapy, fairy tale therapy, phototherapy, film therapy, fine art therapy) helps to correct parents' attitude to their children with special educational needs. In addition, a number of recommendations for the use of art therapy to work with parents of children with special educational needs has been proposed.
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Snityuk, Vitaliy, Marina Antonevich i Anna Didyk. "OPTIMIZATION OF FIRE MONITORING SYSTEM USING THE DEFORMED STARS METHOD". Information systems and technologies security, nr 1 (2) (2020): 60–66. http://dx.doi.org/10.17721/ists.2020.1.60-66.
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In this paper are being considered the aspects of two variables function optimization problem solving, which, in general, is poly-extremal and undifferentiated. The classic methods of continuous optimization are not applicable in this case. One of the most commonly used methods of solving this problem is evolutionary algorithms, which can be divided into two classes. The first class includes algorithms where a potential offspring-solution is generated by two parent-solutions solutions, in the second case, the offspring-solution is generated by one parent-solution. There is deformed star method proposed where the population of parental solutions is 3, 4, and 5 point groups. The application of proposed method is shown to solve the optimization problem of fire monitoring system for buildings, which minimizes the time of its operation. The buildings where fire load can be both permanent and variable are considered. Such buildings include concert halls, nightclubs, supermarkets, logistics facilities and more. Fires at such buildings result in human sacrifice and serious material loss. Timely activation of the fire alarm system have great importance. The objective function of the problem is determined by the distance from the horizontal projections of the detectors to the sources of fire and the probability of triggering the detectors. The solution is optimizing location of fire detectors, taking into account their number and the fire load of the room. The advantages of the developed method over genetic algorithms, evolutionary strategies and differential evolution as the most typical evolutionary algorithms are shown. Numerical experiments were carried out, which showed the increased accuracy of calculations and the increased speed of method convergence.
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Ingersoll, Susan Blaydes, Sarfraz Ahmad, Gregory P. Stoltzfus, Sheylan Patel, Michael J. Radi, Neil J. Finkler, John R. Edwards i Robert W. Holloway. "Functional Characterization of a Fluorescent Highly Tumorigenic Ovarian Cancer Line to Test Cellular Therapy in Experimental Models". International Journal of Gynecologic Cancer 21, nr 3 (kwiecień 2011): 457–65. http://dx.doi.org/10.1097/igc.0b013e31820f4ef0.
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ObjectivesThe objective of this study was to functionally characterize a fluorescent highly tumorigenic ovarian cancer line to test cellular therapy in combination with cytokines or chemotherapies in experimental models.MethodsA fluorescent highly tumorigenic subline (SKOV3-AF2) was derived from the SKOV3 ovarian cancer cell line. Peripheral blood mononuclear cell (PBMC)-mediated cytotoxicity of SKOV3-AF2 in the presence of interleukin 2 (IL-2) and interferon α-2b (IFNα-2b) was assayed by lactate dehydrogenase release. Sensitivity of SKOV3-AF2 cells to polyethylene glycol-IFNα-2b and IL-2 was assayed in a xenograph nude mouse model. Histopathology was performed to determine necrosis and tumor-infiltrating lymphocytes in the solid tumors. Reverse transcriptase-polymerase chain reaction was used for gene expression analyses ofE-cadherinandcysteine-rich 61(CCN1).ResultsThe SKOV3-AF2 subline exhibits increased cytotoxicity (up to 70%), mediated by PBMCs, IL-2, and IFNα-2b, compared with parental SKOV3-red fluorescent protein (RFP) cells. SKOV3-AF2 cells are more tumorigenic in vivo as indicated by tumor incidence, time to sacrifice, tumor weight, and ascitic fluid production. SKOV3-AF2 tumor growth was inhibited by polyethylene glycol-IFNα-2b but not low-dose IL-2. Histopathology revealed that the tumors consisted of poorly differentiated surface epithelial carcinoma. SKOV3-RFP, and -AF2 cell lines as well as -AF2 tumors expressedE-cadherin.SKOV3-AF2 derived tumors expressedCCN1; however, the SKOV3-RFP and SKOV3-AF2 cell lines did not.ConclusionsCharacterization of SKOV3-AF2 cells revealed that it is more susceptible to PBMC-mediated cytotoxicity than SKOV3-RFP and highly tumorigenic in a xenograph model, and AF-2 tumors express genes that promote aggressive behavior. Collectively, our data suggest that the SKOV3-AF2 subline will be a useful tool to test cellular therapy for the treatment of ovarian cancer utilizing experimental models.
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Kind-Kovács, Friederike. "The heroes’ children: Rescuing the Great War’s orphans". Journal of Modern European History 19, nr 2 (24.03.2021): 183–205. http://dx.doi.org/10.1177/1611894421992688.
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World War I and its aftermath produced a particularly vulnerable group of child victims: war orphans. This group included children whose fathers had fallen in battle, who had disappeared, or who had not (yet) returned home. Most of Europe’s war and postwar societies witnessed the massive presence of these child victims, and responded in various ways to rescue them and secure their future survival. This article offers an exploration of the ways in which the Hungarian part of the Austro-Hungarian monarchy, and then later the post-imperial Hungarian state, became invested in providing care and relief to Hungarian war orphans. In contrast to other groups of child victims, whose parents were blamed for neglecting their parental duties, war orphans as the offspring of ‘war heroes’ profited from the public appreciation of their fathers’ sacrifice for the war effort and the Hungarian nation. The public discourse in the contemporary Hungarian media offers a glimpse into the emergence of a new public visibility of these child victims and of a new recognition of the societal obligation to care for them. Exploring World War I and its aftermath as a telling example of political transformation in the 20th century, the article showcases how war orphans were taken to personify essential notions of war- and postwar destruction, while also capturing visions of postwar recovery. It furthermore examines how welfare discourses and relief practices for Hungary’s war orphans were embedded in contemporary gender norms, notions of proper Christian morality and ethnic nationalism. On this basis, the article assesses the ways in which the case of Hungary’s war orphans not only mirrors the professionalization but also the fundamental transformation of child welfare in the aftermath of World War I.
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CUEVAS, STEPHANY. "“Con Mucho Sacrificio, We Give Them Everything We Can”: The Strategic Day-to-Day Sacrifices of Undocumented Latina/o Parents". Harvard Educational Review 89, nr 3 (1.09.2019): 473–96. http://dx.doi.org/10.17763/1943-5045-89.3.473.
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In this research article, Stephany Cuevas explores how undocumented Latina/o parents are engaged in their children's higher education goals and aspirations. Specifically, she investigates how the constraints created by the consequences of their undocumented immigration status, or their “illegality,” impact this engagement. Through in-depth interviews with fifteen undocumented Latina/o parents with children who successfully applied to, were accepted by, and matriculated to a selective public institution in California, Cuevas finds that undocumented parents make intentional day-to-day sacrificios for their children's educational attainment, prioritizing their children's educational financial needs over their own basic needs. While these engagement behaviors are similar to those of other parent populations, Cuevas argues that these investments come at a higher and more personal cost for undocumented immigrant parents. The findings of this study are essential for reconceptualizing research and practice to consider the impact of an immigration status on Latina/o parental engagement.
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Majumder, Amita, i Chayanika Mitra. "Gender bias in household education expenditure: the case of West Bengal". Indian Growth and Development Review 9, nr 2 (14.11.2016): 129–50. http://dx.doi.org/10.1108/igdr-04-2016-0018.
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Purpose This paper aims to detect gender bias in education expenditure on “students”, who are children and young adults, in a household in the rural and the urban sectors of West Bengal. Outlay equivalent ratios have been calculated using the Engel curve approach, where the budget share function is log quadratic in income, to identify items relating exclusively to education of school/college going students. Heckman’s (1979) two-step procedure is used for estimation to address selection bias The 68th round (July 2011 to June 2012) household level consumption expenditure survey data of the National Sample Survey Organisation have been used for the analysis. Design/methodology/approach Engel curve approach is used to capture parental preference for student’s welfare and to find the existence of male student favouritism in the field of education. In case of exclusive adult goods, the addition of a student will reduce the resource allocated for adult goods leading to negative income effect. If a household favours males over females, then that household is likely to sacrifice more for a male student’s education than that for a female student. To address selection bias, Heckman’s two-step procedure has been used. Findings The authors find that not all education items relate exclusively to students of a household. Expenditure on books is not exclusively for students, whereas other educational items, such as stationary and photocopy charges, tuition fees and private coaching fees, are found to be students’ items only. Transport cost is found to be an adult good. Further, we find evidence of pro male bias in expenditure on educational items, and the extent of gender bias is more in the urban sectors compared to the rural sectors in West Bengal. Originality/value The objective of this paper is to identify the educational items exclusively for “students” and to test the difference in the allocation of resources in education, with respect to these items, between a male student and a female student for both sectors in West Bengal, using the outlay equivalent ratios.
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Henrich, R., B. M. Ryan, R. Selby, S. Garthwaite, R. Morrissey i R. I. Freudenthal. "Two-Generation Oral (Diet) Reproductive Toxicity Study of Resorcinol Bis-Diphenylphosphate (Fyrolflex RDP) in Rats". International Journal of Toxicology 19, nr 4 (lipiec 2000): 243–55. http://dx.doi.org/10.1080/10915810050202051.
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Fyrolflex resorcinol bis-diphenylphosphate (RDP) was evaluated in a two-generation reproductive study as part of a program to assess the overall toxicology of this flame retardant. RDP was administered to male and female Sprague-Dawley rats in the diet at concentrations of 1000, 10,000 or 20,000 ppm. The control group was given diet alone. Parental (P1) animals were treated for 10 weeks prior to mating, during the 2-week mating period, throughout gestation, and through lactation until sacrifice. The F1 generation (P1 offspring) was treated following a regimen similar to P1. The F2 generation was not treated. No significant difference in Utter survival was observed between the control and treated groups. Body weights were significantly decreased in P1 rats during the 1st week due to an initial flavor aversion of the test substance in the diet. Body weight, weight gains, and food consumption were decreased in the test substance-treated pups (F1) during lactationand after weaning. These changes were also attributed to a flavor aversion. Anogenital distance was similar in the control and high-dose groups, whereas vaginal opening and preputial separation were delayed in the 10,000 and 20,000 ppm groups, and were considered to be secondary to the reduction in F1 body weight. Neither parents nor offspring exhibited any test substance-related clinical signs of toxicity. Vaginal cytology and cyclicity and male reproductive functions (sperm count, motility, and morphology) were unaffected by treatment. Mating performance was similar in the treated groups relative to the control. No treatment-related lesions were noted in the reproductive organs. Increased liver weight and associated hepatic periportal hypertrophy were observed in the RDP-treated animals (P1 and F1). In conclusion, there were no adverse effects on reproductive performance or fertility parameters associated with RDP administration in the diet. Fyrolflex RDP administered for greater than 13 weeks and up to the entire life span (i.e., F1, from conception to euthanasia) resulted in increased liver weights with associated periportal hypertrophy. This change was considered an adaptive process associated with RDP metabolism in the liver.
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Ryan, B. M., R. Selby, R. Gingell, J. M. Waechter, J. H. Butala, S. S. Dimond, B. J. Dunn, R. House i R. Morrissey. "Two-Generation Reproduction Study and Immunotoxicity Screen in Rats Dosed with Phenol via the Drinking Water". International Journal of Toxicology 20, nr 3 (maj 2001): 121–42. http://dx.doi.org/10.1080/109158101317097700.
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This study evaluated the potential reproductive toxicity of phenol in a rat two-generation reproduction study, which included additional study endpoints, such as sperm count and motility, developmental landmarks, histological evaluation of suspect target organs (liver, kidneys, spleen, and thymus), weanling reproductive organ weights, and an immunotoxicity screening plaque assay. Phenol was administered to 30 Sprague-Dawley rats/sex/group in the drinking water at concentrations of 0, 200, 1000, or 5000 ppm. Parental (P1) animals were treated for 10 weeks prior to mating, during mating, gestation, lactation, and until sacrifice. The F1 generation (P1 offspring) was treated using a similar regimen, while the F2 generation was not treated. After mating, 10 P1 males/group were evaluated using standard clinical pathology parameters and an immunotoxicity screening plaque assay. Significant reductions in water and food consumption were observed in the 5000-ppm group in both generations; corollary reductions in body weight/body weight gain were also observed. Mating performance and fertility in both generations were similar to controls, and no adverse effects on vaginal cytology or male reproductive function were observed. Vaginal opening and preputial separation were delayed in the 5000-ppm group, and were considered to be secondary to the reduction in F1 body weight. Litter survival of both generations was reduced in the 5000-ppm group. Absolute uterus and prostate weights were decreased in the F1 generation at all dose levels; however, no underlying pathology was observed and there was no functional deficit in reproductive performance. Therefore, these findings were not considered to be adverse. No evidence of immunotoxicity was noted in the 5000-ppm group. The effects noted at the high concentration were presumed to be associated with flavor aversion to phenol in the drinking water. Based on a comprehensive examination of all parameters, the no-observable-adverse-effect level (NOAEL) for reproductive toxicity of phenol administered in drinking water to rats is 1000 ppm. The corresponding daily intake of phenol for an adult rat at the NOAEL of 1000 ppm is equivalent to about 70 mg/kg/day for males and 93 mg/kg/day for females.
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Allen, Taryn Ozuna, Yi (Leaf) Zhang i Enrique Romo. "Portraits of Ganas: The College-Going Pathways of Undocumented Students at a Texas HBCU". Journal of Hispanic Higher Education 19, nr 4 (5.09.2018): 335–53. http://dx.doi.org/10.1177/1538192718797926.
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The process of pursuing a higher education degree can be particularly complicated for undocumented students as they navigate the K-16 pipeline. Ganas, or the desire to succeed, is a cultural value that can serve a motivation to overcome educational obstacles. Using portraiture, this article highlights the ways students demonstrated ganas in the ways they prioritized relationships, honored parental sacrifices, and demonstrated resilience. Recommendations for research and practice are offered.
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Pacienza, Natalia A., Nobuo Mizue, Makoto Yoshimitsu, Matthew Scaife, Ronan Foley i Jeffrey A. Medin. "Generation and Implementation of a Novel Murine Xenograft Model for Evaluating Human Hematopoietic Cell-Targeted Gene Therapies for Fabry Disease." Blood 114, nr 22 (20.11.2009): 3576. http://dx.doi.org/10.1182/blood.v114.22.3576.3576.
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Abstract Abstract 3576 Poster Board III-513 Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A (α-gal A). The inability to prevent the progression of galactosylsphingolipid deposition, such as globotriaosylceramide (Gb3), has a significant impact on quality of life and diminishes lifespan from early-onset strokes, progressive renal failure, and heart attacks. Previously, we have demonstrated that gene transfer into murine hematopoietic cells can correct the defect systemically in Fabry mice. The goal of the present study is to create a pure Fabry/NOD/SCID murine line to facilitate the in vivo assessment of human cell-targeted therapies against the disease. The pure line was generated by a “speed congenic” breeding program. The parental generation (F0) was represented by a C3H+C57BL/6 Fabry female mouse (α-gal A−/− scid+/+) and a NOD/SCID male mouse (α-gal A+/0 scid−/−). To generate the α-gal A-/+ scid−/− female mice (F2), the double heterozygous female mice from F1 were mated with NOD/SCID male mice. F3 and all the subsequent generations (until F11) were derived by backcrossing α-gal A-/+ scid−/− female mice with α-gal A+/0 scid−/− male mice. At this point, genome scanning analysis, fluorometric enzymatic assays, and HPLC assessment revealed that the F11 purity was higher than 99%; α-gal A activity was reduced significantly in plasma and Gb3 levels were increased considerably in heart, liver, spleen, kidney and lung, in comparison to NOD/SCID control mice. With the aim of obtaining the pure Fabry/NOD/SCID line, F11 mice were crossed with each other (α-gal A-/+ scid−/− female mice with α-gal A-/0 scid−/− male mice) and then F12 double homozygous female mice (α-gal A−/− scid−/−) were crossed with F12 hemizygous (α-gal A-/0 scid−/−) male mice. For each generation, the genotype of offspring was analyzed by PCR and the absence of T and B cells was confirmed phenotypically by flow cytometry. Currently, this new xenograft model is being validated by using hematopoietic cell targets. To this end, normal human mobilized CD34+ cells were separately transduced with a control (eGFP lentivector) or a bicistronic lentiviral vector encoding the human α-gal A and the human CD25 cell surface marker. 8×105 cells were injected intravenously into sub-lethally irradiated 8-week-old pure Fabry/NOD/SCID male mice. Injected cells were 25% positive for eGFP and 34% positive for human CD25 expression, respectively. Presence of human CD45+ cells, CD45+/CD25+ cells, CD45+/eGFP+ cells and α-gal A activity will be regularly monitored on peripheral blood or plasma, respectively. Near future studies will include Gb3 quantification in tissues at sacrifice and secondary recipient transplantation. As well, Fabry patient bone marrow cells are currently being collected under an approved protocol for testing in this model. In conclusion, this novel xenograft Fabry model is a key tool for developing different therapies for Fabry Disease and will help us to reduce the gap between the bench and the clinic. Disclosures: No relevant conflicts of interest to declare.
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Feuchtbaum, Lisa, George Cunningham i Stan Sciortino. "Questioning the Need for Informed Consent: A Case Study of California's Experience with a Pilot Newborn Screening Research Project". Journal of Empirical Research on Human Research Ethics 2, nr 3 (wrzesień 2007): 3–14. http://dx.doi.org/10.1525/jer.2007.2.3.3.
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California provides mandatory newborn screening for disorders that cause irreversible, severe disabilities if not identified and treated early in life. Parental consent is not required. In 2001, the Genetic Disease Branch was mandated to pilot test a new technology that could identify many additional disorders using the same blood specimen already collected. Study participation required informed consent, which was obtained for 47% of births during the study timeframe. The inability of hospitals to carry out the consent procedure for all newborns resulted in denial of testing and missed cases. If informed consent were waived, all newborns could have been tested. Several empirical questions are posed and each is examined from the perspective of society, the parents and the newborn. It is concluded that the legitimate needs of society and the interests of newborns should not be sacrificed to respond to the autonomy interests of the few parents who did not wish their infant to participate in the study, and that in the future, parental consent should be waived for projects evaluating new screening technologies.
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Lukic, Miodrag L., Eric Mensah-Brown, Sehamuddin Galadari i Allen Shahin. "Lack of Apoptosis of Infiltrating Cells as the Mechanism of High Susceptibility to EAE in DA Rats". Developmental Immunology 8, nr 3-4 (2001): 193–200. http://dx.doi.org/10.1155/2001/32636.
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Dark Agouti (DA) rats are highly susceptible to induction of Th-l-mediated autoimmunity disease, including experimental allergic encephalomyelitis (EAE). In contrast to other susceptible rat strains in which disease is induced only with encephalitogen emulsified in complete Freund's adjuvants (CFA), in DA rats EAE develops after injection of encephalitogen in incomplete Freund's adjuvants (IFA) or Titermax, putative Th-2 directed adjuvant. Lymph node cells derived from immunized DA rats and stimulatedinvitroproduce significantly more Interferon-γ(IFN-γ) than resistant Albino Oxford (AO) rats. However, cells derived from both strains produce large amounts of IL-10 but not IL-4. Immunized lymph node cells derived from EAE susceptible (AO × DA) F1rats induce clinical signs of disease in sublethally irradiated parental DA but not AO rats. The pathohistology of the target tissue in these recipients clearly demonstrated infiltration of mononuclear cells in both parental strains. However, the number of CD4+cells was significantly higher and number of apoptotic cells significantly lower in DA rats sacrificed 8 days after passive transfer. We postulate that in addition to higher IFN-γand TNF-α production, resistance to early apoptosis of the invading cells in the target tissue possibly due to lack of downregulation by TGF-β leads to exceptional susceptibility to EAE in DA rats.
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Oliveira, Jelson Roberto de, i Lucas Piccinin Lazaretti. "Abrão e Isaac: Os sacrifícios do presente e os benefícios do futuro - Sobre o conceito de Temor em Kierkegaard e Hans Jonas". Pensando - Revista de Filosofia 7, nr 14 (26.04.2016): 212. http://dx.doi.org/10.26694/pensando.v7i14.4699.
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Pretende-se nesse ensaio, analisar o conceito de temor a partir da perspectiva de Søren Kierkegaard e Hans Jonas, não necessariamente para estabelecer parâmetros interpretativos, mas para fomentar uma leitura a partir do episódio bíblico do sacrifício de Isaac por seu pai Abraão, neste texto interpretado a partir da heurística do temor, um conceito central da ética da responsabilidade proposta por Jonas como uma ética do futuro. Para tanto, analisaremos o temor como pathos existencial na filosofia kierkegaardiana, para destacar o aspecto emocional que liga o conceito à autoridade parental na filosofia jonasiana e o conduz à hipótese de que é preciso “sacrificar” o presente em benefício do futuro.
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Garib, Ricardo, Priscila Garla, Raquel S. Torrinhas, Ana I. S. Moretti, Marcel C. C. Machado i Dan L. Waitzberg. "Effect of Previous High Glutamine Infusion on Inflammatory Mediators and Mortality in an Acute Pancreatitis Model". Mediators of Inflammation 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/4261419.
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Parenteral glutamine supplementation in acute inflammatory conditions is controversial. We evaluated the inflammatory and survival responses after parenteral glutamine infusion in sodium taurocholate-induced acute pancreatitis (AP) model. Lewis rats received 1 g/kg parenteral glutamine (n=42), saline (n=44), or no treatment (n=45) for 48 h before AP induction. Blood, lung, and liver samples were collected 2, 12, and 24 h after AP to measure serum cytokines levels and tissue heat shock protein (HSP) expression. From each group, 20 animals were not sacrificed after AP for a 7-day mortality study. Serum cytokine levels did not differ among groups at any time point, but the intragroup analysis over time showed higher interferon-γonly in the nontreatment and saline groups at 2 h (versus 12 and 24 h; bothp≤0.05). The glutamine group exhibited greater lung and liver HSP90 expression than did the nontreatment group at 2 and 12 h, respectively; greater liver HSP90 and HSP70 expression than did the saline group at 12 h; and smaller lung HSP70 and liver HSP90 expression than did the nontreatment group at 24 h (allp≤0.019). The 7-day mortality rate did not differ among groups. In experimental AP, pretreatment with parenteral glutamine was safe and improved early inflammatory mediator profiles without affecting mortality.
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Trindade, Zeidi Araujo, i Maria Cristina Smith Menandro. "Pais adolescentes: vivência e significação". Estudos de Psicologia (Natal) 7, nr 1 (styczeń 2002): 15–23. http://dx.doi.org/10.1590/s1413-294x2002000100003.
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Foram investigadas mudanças ocorridas na vida de pais adolescentes e identificados os significados da paternidade e da maternidade para esses jovens. Oito participantes com idades de 16 a 21 anos foram entrevistados com base em roteiro focalizando: mudanças decorrentes da paternidade; significados da paternidade e da maternidade; práticas parentais. Entre as mudanças referidas destacaram-se a perda de liberdade e a inserção no mercado de trabalho. Para eles ser pai significa, principalmente, trabalhar para prover as necessidades da criança e também educar, dar carinho e atenção. A mãe é aquela que cuida e dá carinho, sacrifica-se e é a figura mais importante na vida da criança. As práticas parentais mais mencionadas estavam relacionadas com lazer e brincadeiras. Os dados indicaram a permanência de forte vínculo com os modelos tradicionais de parentalidade, embora tenham mostrado também a emergência de relações afetivas significativas entre pais e filhos.
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Heffez, Dan S., Thaddeus S. Nowak i Janet V. Passonneau. "Nimodipine levels in gerbil brain following parenteral drug administration". Journal of Neurosurgery 63, nr 4 (październik 1985): 589–92. http://dx.doi.org/10.3171/jns.1985.63.4.0589.
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✓ Nimodipine binding to the particulate fraction of gerbil brain homogenate was characterized using tritiated (3H)-nimodipine as the radioactive ligand. Binding was monophasic and saturable, with the apparent affinity constant (KD) = 0.4 nM and the maximum number of binding sites (Bmax) = 12 nmol/kg wet wt. A competitive binding assay was validated for the measurement of nimodipine using gerbil brain as the source of receptors for the drug. Binding characteristics were sufficiently similar in specimens from different animals to allow the use of homogenates from individual animals as the source of both membrane-binding sites and competing ligand. Nimodipine could be detected in the brains of animals sacrificed soon after drug injection, and reached a peak level within 15 minutes. Brain drug level at a given time was a linear function of dose administered. One hour after a 1-mg/kg dose, the level of drug measured in brain was approximately 100 nmol/kg wet wt, more that 200 times the KD. Sufficient drug to mediate a maximal pharmacological effect accumulated in brain even after a dose of only 0.25 mg/kg. Thus, in this species, effective tissue nimodipine levels may be achieved at doses which minimize the risk of systemic hypotension.
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Fotopoulos, Nikos Fotopoulos, Christos Zagkos i Polina Fatourou. "Graduates of Private Schools and the Greek University: Empirical data and sociological interpretations through the period of crisis". Advances in Social Sciences Research Journal 6, nr 12 (2.01.2020): 275–85. http://dx.doi.org/10.14738/assrj.612.7583.
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Ιn modern Greece, the entrance in higher education is considered a kind of social 'fetish'. In this concept, the Greek family diachronically strives to provide its members with an academic perspective, even if this parental choice is linked to many economic and psychological sacrifices. Private education is often associated with the perspective of a better academic and career prospect which is necessarily linked to entrance procedures at the Greek university. During the period (2001-2011) the representation of private school graduates in the total student population seems to be under "representative normality”. Additionally, private school students appear to have the same overall possibilities (neither less nor more) with public school graduates into higher education. However, a deeper sociological analysis demonstrates significant differences in the representation of higher education between public and private schools. This report focuses on private school graduates and more generally on the interpretation of how their entrance into higher education is portrayed.
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López Doblas, Juan, Aina Faus Bertomeu i Rosa Gómez Redondo. "Redes familiares cuidando a personas mayores dependientes: influencia del empleo y del estado civil de los hijos y las hijas". Revista Internacional de Sociología 79, nr 1 (6.04.2021): e176. http://dx.doi.org/10.3989/ris.2021.79.1.19.042.
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Nuestro estudio aborda el cuidado que sus hijos o hijas proveen a las personas mayores, tomando como unidad de análisis a las redes de apoyo en que se enmarcan. El objetivo es doble: indagar en sus estrategias para compaginar esa dedicación con el empleo y en cómo las circunstancias laborales y familiares de cada cual condicionan su participación en el cuidado. En su desarrollo usamos una metodología cualitativa, en concreto entrevistas semiestructuradas para obtener información y teoría fundamentada para analizarla. Los resultados demuestran que, aunque la responsabilidad sea compartida, el estatus laboral de los y las hermanas determina su contribución al cuidado parental. También recogen estrategias comunes para compaginar empleo y cuidado, como el sacrificio de la carrera profesional o la búsqueda de apoyo externo a la familia, así como el rol protagonista que suelen asumir quienes se encuentran en situación de soltería. Dentro de las redes mixtas, además, constatamos que siguen existiendo diferencias de género.
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Purandina, I. Putu Yoga, i Kadek Adyatna Wedananta. "Spirit of Balinese Local Heroes Transformed into Puppets Show on YouTube as ELT Media for Building Students' Character". Jurnal Pendidikan dan Pengajaran 54, nr 1 (9.04.2021): 80. http://dx.doi.org/10.23887/jpp.v54i1.33001.
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Balinese Local Heroes should be role models for all children around Bali. The spirit of the heroes is full of positive characters. Those characters are essential in building a good personality in every single kid. This study aims to analyze Balinese local heroes' effect into puppets show on Youtube as ELT media for building students' character. The research was designed as a qualitative study. The data taken from the observed interaction at the puppets showed on YouTube that students watched. The obtained data were students' and parent's data interviews and questionnaires. The study results showed that Balinese Local Heroes' spirit transformed into puppet shows on YouTube affected students accurately because the media was engaging. Some character values were affected, willingness to sacrifice, bravery, defense of truth and justice, noble, responsible, and patriotic. The social function of all of the values was essential. The values transformed into a positive attitude in social life. The student became a good helper to the people who need help. They clean the environment without any intention and have a responsibility to do their duty as a student.
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Hecker, Matthias, Matthias Rose, Andreas Hecker, Hartmut Dietrich, Martina B. Schaefer, Natascha Sommer, Werner Seeger i Konstantin Mayer. "Immunomodulation by an Omega-6 Fatty Acid Reduced Mixed Lipid Emulsion in Murine Acute Respiratory Distress Syndrome". Journal of Clinical Medicine 9, nr 7 (29.06.2020): 2048. http://dx.doi.org/10.3390/jcm9072048.
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Background: Acute respiratory distress syndrome (ARDS) is associated with both high morbidity and mortality in intensive care units worldwide. Patients with ARDS often require parenteral nutrition with lipid emulsions as essential components. In the present study, we assessed the immunomodulatory and apoptotic effects of a modern, n-6-reduced lipid emulsion mixture in murine ARDS. Methods: Mice received an infusion of either normal saline solution, pure long-chain triglyceride (LCT) emulsion, or SMOF (soybean oil, medium-chain triglycerides, olive oil, and fish oil) before a lipopolysaccharide (LPS) challenge. Mice were sacrificed at different time points (0, 24, or 72 h) after ARDS induction, and an analysis of inflammatory cytokines, protein concentrations, and the cellular composition of the alveolar and interstitial compartments was performed with special focus on alveolar apoptosis and necrosis. Results: Mice infused with SMOF showed decreased leukocyte invasion, protein leakage, myeloperoxidase activity, and cytokine production in alveolar spaces after LPS challenge compared to animals that received LCT. There were fewer cells in the lung interstitium of the SMOF group compared to the LCT group. Both lipid emulsions exerted pro-apoptotic and pro-necrotic properties on alveolar immune cells, with significantly increased necrosis in mice infused with LCT compared to SMOF. Conclusion: SMOF has both anti-inflammatory and pro-resolving influences in murine ARDS. Partial replacement of n-6 fatty acids with n-3/n-9 fatty acids may therefore benefit critically ill patients at risk for ARDS who require parenteral nutrition.
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Ashihara, Eishi, Yoko Nakagawa, Hisayuki Yao, Asumi Yokota, Yasuo Miura, Kazuyuki Takata, Yoshihisa Kitamura, Hideyo Hirai i Taira Maekawa. "Hypoxia-Adapted Myeloma Cells Possess Stem Cell Character". Blood 122, nr 21 (15.11.2013): 3088. http://dx.doi.org/10.1182/blood.v122.21.3088.3088.
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Abstract The prognosis of patients with multiple myeloma (MM) has been improved by the emergence of new molecular targeting agents including proteasome inhibitors and immunomodurating agents. Nevertheless, MM remains incurable at present because it is likely that MM stem cells are resistant to these targeting agents. Thus, it is important to further investigate the biology of MM stem cells to cure the MM patients. We have demonstrated that b-catenin is a novel and attractive target against MM (Ashihara et al. Clin Cancer Res, 2009; Yao et al. Blood Cancer J, 2011). We next investigate novel targets focused on the hypoxic bone marrow (BM) environment. BM is known to have low levels of oxygen, particularly at the epiphysis, which is distant form the BM arterial blood supply. Normal hematopoietic stem cells (HSCs) reside in this hypoxic epiphyseal region “niche”, and HSCs are protected from DNA damage induced by reactive oxygen species. We have previously found that chronic myelogenous leukemia (CML) cells engrafted in the BM survived and proliferated in the severely hypoxic environment and that these hypoxia-adapted (HA) leukemic cells acquired stem cell-like characters (Takeuchi et al. Cell Death Differ, 2010). In this study, we investigated the characteristics of hypoxia-adapted MM (HA-MM) cells. We first confirmed oxygen status in the BM of the MM cell-engrafted mice. Irradiated NOD/SCID mice were inoculated with 2 x 106 AMO-1 cells. After 2 or 4 weeks transplantation, we sacrificed mice and confirmed engraftment. The inoculated MM cells engrafted in the epiphysis in recipient mice after 2 weeks transplantation, and populated endosteum of epiphysis after 4 weeks. These MM cells were positive for pimonidazole, which specifically accumulated in hypoxic cells (< 1.3% O2 concentration). These observations suggested that MM cells resided in the BM are hypoxic. We then established AMO-1, OPM-2, and IM-9 HA-MM cells cultured under hypoxic conditions (O2 1%). These HA cells can continue to proliferate in hypoxic conditions for more than six months. In flow cytometric analysis, the G0 fraction cells as well as side population fraction cells significantly increased in HA-MM cells compared with those in the parental MM cells. We next transplanted parental or HA-MM AMO-1 cells with same cell numbers into irradiated NOD/SCID mice. The survival durations of mice transplanted with HA-AMO-1 cells were significantly shorter than that of mice transplanted with parental cells. Moreover, in serial transplantation experiments, all 5 HA-MM cell-transplanted mice died of MM whereas 1 out of 5 parental MM cell-transplanted mice (Figure 1). Quantitative RT-PCR analysis demonstrated that Sox2, Oct3, and Nanog mRNA transcripts increased in the HA-MM AMO-1 cells (Figure 2). We next investigated the signaling pathway activated in HA-MM cells. Interestingly, phosphorylated Smad2 expression was increased in HA-AMO-1 cells. These findings suggest that HA-MM cells possess stem cell-like character, and these cells may provide a useful model to investigate the mechanism of MM stem cells (myeloma-initiating cells) resistant to molecular target agents. Disclosures: No relevant conflicts of interest to declare.
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Takeuchi, Miki, Shinya Kimura, Junya Kuroda, Takashi Ushiki, Makoto Kawatani, Hiroyuki Osada, Kazuo Umezawa i in. "Glyoxalase-I Inhibition Eliminates Hypoxia-Adapted CML Cells Resistant to Imatinib, Dasatinib, and INNO-406". Blood 112, nr 11 (16.11.2008): 3185. http://dx.doi.org/10.1182/blood.v112.11.3185.3185.
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Abstract The development of ABL tyrosine kinase inhibitor (TKI), imatinib mesylate and second-generation ABL TKIs such as dasatinib and nilotinib have dramatically improved the efficacy of chronic myeloid leukemia (CML) treatment, but “total cell kill” may not be possible with TKIs alone because they do not appear to eliminate CML stem cells. Although the CML stem cell niche has not yet been clearly identified, it may be a hypoxic environment, like that of normal hematopoietic stem cells, which mainly exists in the low oxygen-consuming region in the bone marrow (BM). Notably, most cancer cells that adapt to hypoxia are resistant to a variety of cell-death stimuli. Thus, we hypothesized that CML cells, in particular CML stem cells, adapt to hypoxia for their persistence. To test this notion, we first examined the oxygenated status of CML cells in vivo by transplanting K562 cells into NOD/SCID/gcnull (NOG) mice. Six weeks later, pimonidazole, which specifically accumulates in tissues with <1.3% O2, was administered and the mice were sacrificed. The K562 cells had mainly engrafted into the epiphysis, which is presumed to be a particularly hypoxic environment, and these engrafted cells were positively stained by antibody to pimonidazole. This suggests that the engrafted leukemic cells survived in hypoxic conditions. To investigate the role that adaptation to hypoxia plays in CML-cell persistence, we generated two hypoxia-adapted cell lines that can survive in hypoxic conditions and identified their unique characteristics compared to their parental cells. For this, the CML-derived cell lines K562, KCL-22, BV173 and MYL were cultivated in 1.0% O2 for two weeks. Two subclones that survived were obtained from K562 and KCL22 and were denoted as K562/HA and KCL22/HA, respectively. Both cell lines proliferated continuously for months in 1.0% O2 conditions in RPMI1640 medium containing 10% FCS but lacking any additional nutrient supplies, although their growth was slower than that of their parental counterparts under 20% oxygen in the same media. We found that, compared to their parental counterparts, K562/HA and KCL22/HA had higher glyoxalase-I (Glo-I) expression and kinase activity. Glo-I is an enzyme that detoxifies methylglyoxal, a cytotoxic byproduct of glycolysis. Interestingly, BCR-ABL phosphorylation was suppressed in both hypoxia-adapted cell lines. However, the phosphorylation of AKT, STAT and ERK was unchanged in these hypoxia-adapted cells, which suggests the presence of alternative hypoxia-specific activation pathways. When NOG mice were inoculated with equivalent numbers of K562/HA and K562 cells, K562/HA engrafted more rapidly than K562 and K562/HA-engrafted mice died earlier than K562-engrafted mice. Thus, adaptation to hypoxia is crucial for the engraftment and proliferation of CML cells in the BM. Notably, compared to their parental counterparts, K562/HA and KCL22/HA cells were less sensitive to TKIs (imatinib, dasatinib, and INNO-406) and alkylating agents (daunorubicin and busulfan). However, they were more sensitive to Glo-I inhibitors such as S-p-bromobenzylglutathione cyclopentyl diester (BBGC), 2-crotonyloxymethyl- 4,5,6-trihydroxycylohex-2-enone (COTC), and methyl-gerfelin. Thus, Glo-I enzymatic activity plays an important role in CML-cell adaptation to hypoxic environments, which means Glo-1 may be an alternative molecular target for therapies aiming to eliminate those CML cells that adapt to hypoxia and thereby acquire resistance to conventional chemotherapies, including those based on TKIs. Indeed, when K562/HA-transplanted mice were treated with 100mg/kg/day BBGC for 8 days or left untreated, the treated mice survived longer than the untreated mice. In contrast, the survival of mice transplanted with the parental cell line K562 did not change whether they were treated with BBGC or left untreated. Thus, Glo-1 enzymatic activity plays an important role in CML-cell survival under hypoxic environmental conditions and Glo-I inhibitors could be promising agents for the elimination of CML (stem) cells that persist in the hypoxic BM milieu
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Miles, Lindsey A., Nagyung Baik, Stan Krajewski, Robert J. Parmer i Barbara M. Mueller. "The Novel Plasminogen Receptor, Plg-RKT, and Breast Cancer Progression". Blood 118, nr 21 (18.11.2011): 853. http://dx.doi.org/10.1182/blood.v118.21.853.853.
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Abstract Abstract 853 The ability of tumor cells to bind plasminogen is highly correlated with their invasive and metastatic potential. Here we evaluate cell surface plasminogen binding in human breast cancer. In a xenograft model for aggressive, triple-negative human breast cancer, tumor cells harvested from orthotopic mammary fat pad (mfp) tumors of the invasive human breast cancer line, MDA-MB-231, exhibit dramatic increases in tumor growth and lung and lymph node metastases, compared to parental cells. The breast cancer cells isolated from the mfp have been designated as 231mfp cells. Although the levels of most secreted proteins are similar, the plasminogen activators, urokinase-type plasminogen activator (uPA) and tissue type plasminogen activator (tPA) are highly upregulated in 231mfp cells, compared with MDA-MB-231 parental cells, suggesting a role for the plasminogen activation system in the differences in growth and metastasis between these two cell lines (Jessani et al., Proc Natl Acad Sci USA 101:13756, 2004). Further evaluation of the plasminogen activation system in this model revealed that plasminogen bound to both 231mfp and MDA-MB-231 cells and plasminogen binding was specifically inhibited by the lysine analog, ε-aminocaproic acid (EACA). 231mfp cells exhibited a 3-fold greater capacity for plasminogen compared to MDA-MB-231 cells: Quantitative FACS analysis yielded a Bmax of 3.8 ± 0.5 × 105 plasminogen binding sites with a Kd of 1.2 μM for the 231 mfp cells and a Bmax of 1.2 ± 0.3 × 105 binding sites with a Kd of 1.5 μM for the parental cells. We recently discovered a novel cell surface receptor for plasminogen, Plg-RKT (Andronicos et al., Blood 115:1319, 2010). Plg-RKT enhances enzymatic activation of plasminogen to plasmin and localizes and spatially orients plasmin on the cell surface. We compared cell-surface expression of Plg-RKT on 231mfp and MDA-MB-231 cells using a specific monoclonal antibody raised against the C-terminus of human Plg-RKT, termed mAb7H1. In FACS analysis with mAB7H1, expression of Plg-RKT was markedly (5-fold) higher on 231mfp cells, compared to the parental cells. These data were confirmed in Western blotting. To further determine expression of Plg-RKT in breast cancer, human tissues were stained with anti-Plg-RKT antibodies. We found very high expression of Plg-RKT in human invasive ductal carcinoma and ductal carcinoma in situ and minimal expression in normal breast ducts and lobules in control subjects. We considered whether Plg-RKT expressed on breast cancer cells can a therapeutic target and we tested the ability of anti-Plg-RKT mAb7H1 to inhibit lung metastasis of 231mfp cells in immune deficient mice. Mice were injected into the tail vein with cells either mixed with mAb7H1 or with buffer control. The antibody-treated group received a second dose of mAb7H1 24 hr later. Four weeks after tumor cell injection, mice were sacrificed and tumor foci on the lungs were compared between the two groups. Anti-Plg-RKT mAb7H1 markedly reduced the number of 231mfp lung metastases per mouse: mean number of lung foci in the mAb7H1 treated group was 109 (± 47.8) and in the vehicle-treated control group 270.4 (± 61.7), probability of no difference between the groups by t-test P<0.05. The size distribution of the individual foci was not different between the groups. These data demonstrate that anti-Plg-RKT mAb7H1 has activity in the mouse model of metastatic breast cancer and suggest that it interferes with an early step in the establishment of lung metastases. In summary, the highly metastatic 231mfp breast cancer cells have increased plasminogen binding capacity and increased expression of the plasminogen receptor, Plg-RKT, compared to parental MDA-MB-231 cells. Plg-RKT was highly expressed in human breast cancer tissue but not in normal mammary glands. Furthermore, anti-Plg-RKT mAb inhibited establishment of lung metastases in a model of human breast cancer. Therefore, the presence of Plg-RKT on breast cancer cells may represent a new control point in the establishment of breast cancer metastases. Disclosures: No relevant conflicts of interest to declare.
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Chong, Si Jack, Yong Chiat Wong, Jian Wu, Mui Hong Tan, Jia Lu i Shabbir M. Moochhala. "Parecoxib Reduces Systemic Inflammation and Acute Lung Injury in Burned Animals with Delayed Fluid Resuscitation". International Journal of Inflammation 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/972645.
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Burn injuries result in the release of proinflammatory mediators causing both local and systemic inflammation. Multiple organ dysfunctions secondary to systemic inflammation after severe burn contribute to adverse outcome, with the lungs being the first organ to fail. In this study, we evaluate the anti-inflammatory effects of Parecoxib, a parenteral COX-2 inhibitor, in a delayed fluid resuscitation burned rat model. Anaesthetized Sprague Dawley rats were inflicted with 45% total body surface area full-thickness scald burns and subsequently subjected to delayed resuscitation with Hartmann’s solution. Parecoxib (0.1, 1.0, and 10 mg/kg) was delivered intramuscularly 20 min after injury followed by 12 h interval and the rats were sacrificed at 6 h, 24 h, and 48 h. Burn rats developed elevated blood cytokines, transaminase, creatinine, and increased lung MPO levels. Animals treated with 1 mg/kg Parecoxib showed significantly reduced plasma level of CINC-1, IL-6, PGEM, and lung MPO. Treatment of 1 mg/kg Parecoxib is shown to mitigate systemic and lung inflammation without significantly affecting other organs. At present, no specific therapeutic agent is available to attenuate the systemic inflammatory response secondary to burn injury. The results suggest that Parecoxib may have the potential to be used both as an analgesic and ameliorate the effects of lung injury following burn.
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Kovago, Csaba, Nora Meggyeshazi, Gabor Andocs i Andras Szasz. "Report of the Pilot Study Done for the Proposed Investigation on the Possible Synergic Effect between High-Dose Ascorbic Acid Application and Oncothermia Treatment". Conference Papers in Medicine 2013 (23.05.2013): 1–2. http://dx.doi.org/10.1155/2013/386913.
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According to recent investigations, the parenteral application of ascorbic acid (vitamin C) at high doses has significant antitumor activity in in vitro assays. The goal of our experiment was to determine the possible potentiating effect of application of high dose pH-neutralized ascorbic acid to the normal oncothermia treatment method. The NMRI mice were inoculated with C26 murine colon carcinoma cell line subcutaneously at both of their femoral regions and were kept till the tumors reached symmetrically 10 mm in diameter. We created four experimental groups, containing 5 male and 5 female animals in each. Both vitamin-C and oncothermia treatments were applied once; ascorbic acid was applied intra-peritoneally. Oncothermia treatment was applied only to the right limb tumor; the other side will be used as internal control. After the treatment, the animals were sacrificed, and all tumors were removed and analyzed histopathologically. Our main question centers on the comparison of the cell destruction ratio of the various applied treatment regimes, and studies the possible synergy or additive cross-potentiating of the methods. The results of this experiment turned out to be controversial, since the ascorbic acid did not change the remission rate of the allografts and showed no synergy with oncothermia.
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Teixeira, Vitor, Ibrahim Mohamed i Jean-Claude Lavoie. "Neonatal Vitamin C and Cysteine Deficiencies Program Adult Hepatic Glutathione and Specific Activities of Glucokinase, Phosphofructokinase, and Acetyl-CoA Carboxylase in Guinea Pigs’ Livers". Antioxidants 10, nr 6 (12.06.2021): 953. http://dx.doi.org/10.3390/antiox10060953.
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Premature neonates are submitted to an early-life oxidative stress from parenteral nutrition, which is vitamin C (VC) deficient and induces low endogenous levels of glutathione. The oxidative stress caused by these deficiencies may permanently affect liver glycolysis and lipogenesis. This study evaluates the short- and long-term effects of neonatal VC and cysteine deficient diets on redox and energy metabolism. Three-day-old Hartley guinea pigs from both sexes were given a regular or a deficient diet (VC, cysteine, or both) until week 1 of life. Half of the animals were sacrificed at this age, while the other half ate a complete diet until 12 weeks. Liver glutathione and the activity and protein levels of glucokinase, phosphofructokinase, and acetyl-CoA-carboxylase were measured. Statistics: factorial ANOVA (5% threshold). At 1 week, all deficient diets decreased glutathione and the protein levels of glucokinase and phosphofructokinase, while cysteine deficiency decreased acetyl-CoA-carboxylase levels. A similar enzyme level was observed in control animals at 12 weeks. At this age, VC deficiency decreased glutathione, while cysteine increased it. Acetyl-CoA-carboxylase protein levels were increased, which decreased its specific activity. Early-life VC and cysteine deficiencies induce neonatal oxidative stress and an adult-like metabolism, while predisposing to increased lipogenic rates during adulthood.
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MONSI, A., M. A. BAKST i M. C. CECIL. "CHANGES IN BLOOD PARAMETERS IN BREEDER TOMS FOLLOWING SUBCUTANEOUS INJECTION WITH CADMIUM". Nigerian Journal of Animal Production 23, nr 2 (12.01.2021): 134–40. http://dx.doi.org/10.51791/njap.v23i2.2257.
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Alterations in blood biochemical values of Yearling breeder toms following parenteral administration of cadmium (Cd) were well evaluated. Each treated member of a pair of (total 24 pairs) 0f toms received a single dose of 4.5mg of Cd per kg. body weight (0.04-mole). The birds were sacrificed at 0,6,24 and 192 hours : post-treatment. Highly significant (P<0.0001).increase in serum Cd concentration was observed in the Cd-injected toms, Reduction in the blood have been used to produce useful serum Cd (P<0.05) at the successive post-necropsy periods indicated systematic clearance of the metal from the fluid. Nearly 50 percent eliminated by 24 h post-treatment. Serum changes glutamic pyruvic transaminase (SGPT) was due to the similarly increased (P<0.05) in the Cd-treated birds and was presumed to have originated mainly from damaged skeletal muscle tissues. The cadmium treatment did not affect (P>0.05) serum testosterone level, total protein, total haemoglobin, lactate dehydrogenase, packed cell volume or serum glutamic oxaloacetic transaminase. It was concluded from these observations that the Cd treatment did not seem to have interfered seriously with renal or hepatic functions, iron, copper and zinc metabolism or caused significant damage to myocardial issue.
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Jenks, Peter J., Richard L. Ferrero, Jacques Tankovic, Jean-Michel Thiberge i Agnès Labigne. "Evaluation of Nitrofurantoin Combination Therapy of Metronidazole-Sensitive and -Resistant Helicobacter pyloriInfections in Mice". Antimicrobial Agents and Chemotherapy 44, nr 10 (1.10.2000): 2623–29. http://dx.doi.org/10.1128/aac.44.10.2623-2629.2000.
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ABSTRACT The main objectives of this study were to determine whether the nitroreductase enzyme encoded by the rdxA gene ofHelicobacter pylori was responsible for reductive activation of nitrofurantoin and whether a triple-therapy regimen with nitrofurantoin was able to eradicate metronidazole-sensitive and -resistant H. pylori infections from mice. The susceptibilities to nitrofurantoin of parent and isogenicrdxA mutant strains (three pairs), as well as a series of matched metronidazole-sensitive and -resistant strains isolated from mice (30) and patients (20), were assessed by agar dilution determination of the MIC. Groups of mice colonized with the metronidazole-sensitive H. pylori SS1 strain or a metronidazole-resistant rdxA SS1 mutant were treated with either metronidazole or nitrofurantoin as part of a triple-therapy regimen. One month after the completion of treatment the mice were sacrificed and their stomachs were cultured for H. pylori. The nitrofurantoin MICs for all strains tested were between 0.5 and 4.0 μg/ml. There was no significant difference between the susceptibility to nitrofurantoin of the parental strains and those of respectiverdxA mutants or between those of matched metronidazole-sensitive and -resistant H. pylori isolates. The regimen with metronidazole eradicated infection from all eight SS1-infected mice and from one of eight mice inoculated with therdxA mutant (P ≤ 0.001). The regimen with nitrofurantoin failed to eradicate infection from any of the six SS1-infected mice (P ≤ 0.001) and cleared infection from one of seven mice inoculated with the rdxA mutant. These results demonstrate that, despite the good in vitro activity of nitrofurantoin against H. pylori and the lack of cross-resistance between metronidazole and nitrofurantoin, eradication regimens involving nitrofurantoin are unable to eradicate either metronidazole-sensitive or -resistant H. pylori infections from mice.
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Shirasaki, Ryosuke, Haruko Tashiro, Yoko Oka, Toshihiko Sugao, Nobu Akiyama, Kazuo Kawasugi i Naoki Shirafuji. "Chronic Myelogenous Leukemia Cells Contribute to a Bone Marrow-Stroma in In Vivo NOD/SCID Mouse System." Blood 114, nr 22 (20.11.2009): 2191. http://dx.doi.org/10.1182/blood.v114.22.2191.2191.
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Abstract Abstract 2191 Poster Board II-168 Aims: The stroma-forming cells in a bone marrow are derived from hematopoietic stem cells. We reported previously that non-adherent leukemia blast cells converted into myofibroblasts to create a microenvironment for proliferation of leukemia blasts in vitro. In this report we demonstrate that with severe combined immunodeficiency (SCID) mouse system chronic myelogenous leukemia (CML) cells are also differentiated into myofibroblasts to contribute to a bone marrow-stroma in vivo. Materials and Methods: Bone marrow cells were collected from informed CML patients, from which mononuclear cells were separated with density-gradient sedimentation method. After discarded an adherent cell-fraction, non-adherent mononuclear cells were injected to the priory 2.5 Gray-irradiated non-obese diabetes (NOD)/SCID mice intravenously. For the inactivation of NK cells, anti-Asialo GM1 antibody was injected intra-peritoneally prior to the transplantation, and on each 11th day thereafter. Blood was collected to monitor Bcr-Abl transcript, and mice were sacrificed after chimeric mRNA was demonstrated. Bone marrow cells were obtained, and sorted with anti-human CD133 antibody and -CD106 to select CML-derived human stromal myofibroblasts referred to the in vitro data. The isolated positive fraction was further cultured, and the biological and the molecular characteristics were analyzed. Results and Discussion: When non-adherent CML cells were transplanted to NOD/SCID mice, CML cells were engrafted after 2 months. In the murine bone marrow human stromal cells were identified, in which BCR and ABL gene was fused with FISH analysis. When the parental CML cells were cultured on the CML-derived myofibroblasts, CML cells grew extensively in a vascular endothelial growth factor-A-dependent fashion. These results indicate that CML cells can create their own microenvironment for proliferation in vivo. Disclosures: No relevant conflicts of interest to declare.
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Makio, Albina, Lillian Musila, Eddy Okoth Odari, Juliette Rose Ongus i Rosemary Sang. "The Potential of O’nyong-nyong Virus Strain SG650 Murine Monoclonal Antibodies for Detection of O’nyong-nyong and Chikungunya Viruses". East African Journal of Health and Science 3, nr 1 (5.08.2021): 97–114. http://dx.doi.org/10.37284/eajhs.3.1.377.
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O’nyong-nyong virus (ONNV) and Chikungunya virus (CHIKV) are antigenically related alphaviruses responsible for febrile illnesses common to the tropics and associated with relatively high morbidity and mortality. Murine monoclonal antibodies (mAbs) targeting alphaviruses like Chikungunya have been developed and used to make commercially available kits. However, few studies have been conducted to develop antibodies specific to ONNV and no commercial kits are available for use in endemic regions where outbreak potential is high. We demonstrate the potential of in-house generated monoclonal antibodies against ONNV to detect both ONNV and CHIKV. The objective of this study was to generate mAbs using hybridoma technology, characterize the developed mAbs, determine their specificity against selected alphaviruses and check their diagnostic potential using an indirect IgG enzyme-linked immunosorbent assay (ELISA) and focus neutralization assay (FRNT50). BALB/c mice were immunized with ONNV purified proteins from ONNV infectious culture fluid. After four rounds of booster injections, the mice were sacrificed, spleen cells harvested and fused with parental myeloma cells then cultured in selective media and the successful hybrid clones with antibody-producing ability purified to yield the desired mAbs. Five monoclonal antibodies targeting the ONNV E1 protein of isotypes IgG2a/kappa, IgG2b/kappa and IgM/kappa (P1B12, P1E9, P1G11, P1B4 and P1G6) demonstrated a potential to detect both ONNV and CHIKV isolates by indirect IgG ELISA but no potential for neutralization of the viruses by FRNT50. This study demonstrates the potential efficacy of in-house serological tools as an alternative in the absence of commercial assays in screening and diagnosis of ONN and CHIK viruses which are often co-circulating. It is our recommendation that this work may be pursued further to design and optimize ELISA assays, using the developed mAbs, for the detection of both ONN and CHIK viruses in the research laboratory set-up
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Karembe, Hamadi, Daniel Sperling, Nathalie Varinot, Reynald Magnier, Mathieu Peyrou, Nicolas Guerra, Jiří Smola, Jan Vasek, Barbara Hinney i Anja Joachim. "Absorption and Distribution of Toltrazuril and Toltrazuril Sulfone in Plasma, Intestinal Tissues and Content of Piglets after Oral or Intramuscular Administration". Molecules 26, nr 18 (16.09.2021): 5633. http://dx.doi.org/10.3390/molecules26185633.
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Piglet coccidiosis due to Cystoisospora suis is a major cause of diarrhea and poor growth worldwide. It can effectively be controlled by application of toltrazuril (TZ), and oral formulations have been licensed for many years. Recently, the first parenteral formulation containing TZ in combination with iron (gleptoferron) was registered in the EU for the prevention of coccidiosis and iron deficiency anemia, conditions in suckling piglets requiring routine preventive measures. This study evaluated the absorption and distribution of TZ and its main metabolite, toltrazuril sulfone (TZ-SO2), in blood and intestinal tissues after single oral (20 mg/kg) or single intramuscular (45 mg/piglet) application of TZ. Fifty-six piglets were randomly allocated to the two treatment groups. Animals were sacrificed 1-, 5-, 13-, and 24-days post-treatment and TZ and TZ-SO2 levels were determined in blood, jejunal tissue, ileal tissue, and mixed jejunal and ileal content (IC) by high performance liquid chromatography (HPLC). Intramuscular application resulted in significantly higher and more sustained concentrations of both compounds in plasma, intestinal tissue, and IC. Higher concentrations after oral dosing were only observed one day after application of TZ in jejunum and IC. Toltrazuril was quickly metabolized to TZ-SO2 with maximum concentrations on day 13 for both applications. Remarkably, TZ and TZ-SO2 accumulated in the jejunum, the primary predilection site of C. suis, independently of the administration route, which is key to their antiparasitic effect.
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Duprex, W. Paul, Stephen Mcquaid, Branka Roscic-Mrkic, Roberto Cattaneo, Cecilia Mccallister i Bert K. Rima. "In Vitro and In Vivo Infection of Neural Cells by a Recombinant Measles Virus Expressing Enhanced Green Fluorescent Protein". Journal of Virology 74, nr 17 (1.09.2000): 7972–79. http://dx.doi.org/10.1128/jvi.74.17.7972-7979.2000.
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ABSTRACT This study focused on the in vitro infection of mouse and human neuroblastoma cells and the in vivo infection of the murine central nervous system with a recombinant measles virus. An undifferentiated mouse neuroblastoma cell line (TMN) was infected with the vaccine strain of measles virus (MVeGFP), which expresses enhanced green fluorescent protein (EGFP). MVeGFP infected the cells, and cell-to-cell spread was studied by virtue of the resulting EGFP autofluorescence, using real-time confocal microscopy. Cells were differentiated to a neuronal phenotype, and extended processes, which interconnected the cells, were observed. It was also possible to infect the differentiated neuroblastoma cells (dTMN) with MVeGFP. Single autofluorescent EGFP-positive cells were selected at the earliest possible point in the infection, and the spread of EGFP autofluorescence was monitored. In this instance the virus used the interconnecting processes to spread from cell to cell. Human neuroblastoma cells (SH-SY-5Y) were also infected with MVeGFP. The virus infected these cells, and existing processes were used to initiate new foci of infection at distinct regions of the monolayer. Transgenic animals expressing CD46, a measles virus receptor, and lacking interferon type 1 receptor gene were infected intracerebrally with MVeGFP. A productive infection ensued, and the mice exhibited clinical signs of infection, such as ataxia and an awkward gait, identical to those previously observed for the parental virus (Edtag). Mice were sacrificed, and brain sections were examined for EGFP autofluorescence by confocal scanning laser microscopy over a period of 6 h. EGFP was detected in discrete focal regions of the brain and in processes, which extended deep into the parenchyma. Collectively, these results indicate (i) that MVeGFP can be used to monitor virus replication sensitively, in real time, in animal tissues, (ii) that infection of ependymal cells and neuroblasts provides a route by which measles virus can enter the central nervous system in mouse models of encephalitis, and (iii) that upon infection, the virus spreads transneuronally.
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Tashiro, Haruko, Ryosuke Shirasaki, Yoko Oka, Toshihiko Sugao, Nobu Akiyama, Kazuo Kawasugi i Naoki Shirafuji. "Acute Myelogenous Leukemia Blasts Contribute to a Bone Marrow-Stroma in In Vivo NOD/SCID Mouse System.." Blood 114, nr 22 (20.11.2009): 1621. http://dx.doi.org/10.1182/blood.v114.22.1621.1621.
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Abstract Abstract 1621 Poster Board I-647 Aims: Cancer stem cell theory has been developed, and whose precise characteristics have been reported. However, there have been no reports on the differentiation of cancer stem cells into the environmental stromal cells. We reported previously that non-adherent acute myelogenous leukemia (AML) cells were differentiated into myofibroblasts to create a microenvironment for proliferation of AML blasts in vitro. In this report we demonstrate that with severe combined immunodeficiency (SCID) mouse system AML blast cells also convert to myofibroblasts to form stroma in vivo. Materials and Methods Bone marrow cells were collected from informed AML (M2) patients who had chromosomal translocation of RUNX1 and ETO, from which mononuclear cells were separated with density-gradient sedimentation method. After discarded an adherent cell-fraction, the non-adherent mononuclear cells were injected to the 3.0 Gray-irradiated non-obese diabetes (NOD)/SCID mouse intravenously. For the inactivation of NK cells, anti-Asialo GM1 antibody was injected intra-peritoneally prior to the transplantation, and on each 11th day thereafter. Blood was collected to monitor Runx1 and ETO fusion transcript, and mice were sacrificed after chimeric mRNA was observed. Bone marrow cells were obtained, and sorted with anti-human CD133 antibody and -CD106 to select AML-derived human stromal myofibroblasts referred to the in vitro data. The isolated positive fraction was further cultured, and the biological and the molecular characteristics were analyzed. Results and Discussion When non-adherent AML (M2) blast cells were transplanted to NOD/SCID mice, cells were engrafted after 10 weeks. In murine bone marrow cells human stromal cells were identified, in which RUNX1 and ETO gene was fused with FISH analysis. When the parental AML blast cells were cultured on the expanded AML-derived myofibroblasts, AML cells grew extensively. These results indicate that AML cells can create their own microenvironment for proliferation in vivo. Disclosures No relevant conflicts of interest to declare.
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Elif, Memisoglu, Jeffrey A. Cooper i Robert E. Fleming. "Upregulation Of Hepcidin Expression By Lactoferrin Administration To Pre-Weanling Mice". Blood 122, nr 21 (15.11.2013): 964. http://dx.doi.org/10.1182/blood.v122.21.964.964.
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Abstract Background Hepcidin is a peptide hormone produced in hepatocytes which regulates dietary iron absorption and systemic iron distribution. The hepatic expression of the hepcidin gene is regulated by signals which reflect body iron status and erythropoietic activity. The regulation of hepcidin by iron status includes a signal from the circulating transferrin via hepatocellular transferrin receptor (TfR2). Lactoferrin is a member of the transferrin family of iron-binding glycoproteins found in high concentrations in milk. Lactoferrin has a well described role in host defense; however, its in iron metabolism is less clear. Like transferrin, lactoferrin will deliver iron to hepatocytes but unlike transferrin, lactoferrin cannot deliver iron to erythroid cells. Lactoferrin does not interact with TfR1 or TfR2. We took advantage of these properties of lactoferrin to determine if delivering iron to the liver (but not erythron) in a form which is independent on transferrin and its receptors could regulate hepcidin. Methods To take advantage of the naturally-occuring low iron and low hepcidin states at this developmental stage, experiments were performed on pre-weanling mice. Mice at 12-14d (pre-weanling) were administered human lactoferrin equivalent to 2 mg/kg iron (n=10) or carrier (n=10) intraperitoneally (IP) and sacrificed 6 h later. Other mice were administered a comparable IP dose of transferrin (n=5) or carrier (n=4). Additional groups of mice were delivered Lf (n=8) or carrier (n=7) enterally (by orogastric tube), and the sacrificed 6h or 24h later. Liver hepcidin (Hamp1) mRNA was measured by real-time RT-PCR, normalized to beta actin expression, and analyzed by commercial software (Rest 2007, Qiagen). Liver iron distribution was determined histochemically in tissue sections by modified Perls' staining. Results Parenteral administration of lactoferrin in pre-weanling mice was associated with a 32-fold increase in liver Hamp1 expression after 6 hours (P<0.001). This compares with an only 4.5 fold increase in Hamp1 expression 6h after a comparable dose of transferrin. Enteral lactoferrin likewise resulted in a ∼30-fold increase in Hamp1 expression (P<0.005) after 24 hours. Iron delivered to the liver from lactoferrin was distributed in sinusoidal lining cells as well as hepatocytes. Conclusions Exogenously administered iron-rplete lactoferrin increases liver Hamp1 expression in pre-weanling mice. These observations demonstrate that iron delivery to the liver in a form not dependent upon transferrin or its receptors upregulates hepcidin expression. These findings moreover raise the possibility that lactoferrin-mediated changes in hepcidin expression may contribute to reported benefits of supplemental lactoferrin on host defense. Disclosures: No relevant conflicts of interest to declare.