New Complex Chromosomal Translocation in Chronic Myeloid Leukaemia: t(9;18;22)(q34;p11;q11)

A Chronic myeloid leukaemia (CML) case with a new complex t(9;18;22)(q34;p11;q11) of a 29-year-old man is being reported. For the first time, this translocation has been characterized by karyotype complemented with fluorescence in situ hybridization (FISH). In CML, the complex and standard translocations have the same prognosis. The patient was treated with standard initial therapy based on hydroxyurea before he died due to heart failure four months later. Our finding indicates the importance of combined cytogenetic analysis for diagnosis and guidance of treatment in clinical diagnosis of CML

A Combination of Systemic and Intracranial Anti-CD25 Immunotherapy Elicits a Long-Time Survival in Murine Model of Glioma

Abrogating the suppression of glioma-infiltrating Tregs in the periphery and the central nervous system is essential to successful glioma rejection. We sought to improve the immune response in glioma-bearing mice, by investigating new strategies using the anti-CD25 immunotherapy. We found a complete long-term survival of glioma-bearing mice treated with a combination of systemic and intracranial anti-CD25 mAb immunotherapy as compared to systemic administration of anti-CD25 mAb. In addition, the group of mice that had been cured by the combined anti-CD25 mAb showed long-term survival without late tumor relapse when challenged with the GL261 glioma. The antitumor immune response was investigated by analysis of antitumor immune response (CTL). Results showed that the use of the combined injections of anti-CD25 mAb induced efficient targeting of Tregs expansion inside and outside of the brain and altered Tregs trafficking in the bone marrow and brain areas where antitumor immunity was primed

An increase in CD4+CD25+FOXP3+ regulatory T cells in tumor-infiltrating lymphocytes of human glioblastoma multiforme1

The subpopulation of CD4+CD25+ immunoregulatory T (Tr) cells constitutes 5%–10% of CD4+ cells in humans. These cells play a crucial role in the control of tumor immune response. In this study, we evaluated the distribution of Tr cells in tumor-infiltrating lymphocytes of human glioblastoma multiforme and examined the difference between the brain and autologous blood with respect to Tr cells. Glioma samples from 10 patients were classified as WHO grade IV astrocytoma. Control samples were obtained from patients undergoing resection of a seizure focus. The samples were analyzed by flow cytometry to determine the frequency of Tr cells and by real-time PCR for forkhead box P3 (FOXP3) expression. We then examined the expression of CD62L, CD45RO, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and assessed the functionality of Tr cells in vitro. There was a significant difference in the number of FOXP3-expressing CD4+CD25+ T cells within glioma-infiltrating lymphocytes as compared to controls (P < 0.01). This difference was further observed in studies of autologous patient blood and control blood. The expression level of FOXP3 mRNA was high in Tr cells and weak in CD4+CD25− T cells. Moreover, the expression of CD62L and CTLA-4 was elevated in glioma Tr cells as compared to that in the controls. These cells were also CD45RO positive. Functional assays confirmed the suppressive activity of Tr cells in patients with glioma. The expression of CD4+CD25+FOXP3+ T cells was significantly higher in patients with glioblastoma multiforme than in controls. This increase in the frequency of Tr cells that display suppressive activity might play a role in modulation of the immune response against glioma. In light of these findings, Tr cells may represent a potential target for immunotherapy of malignant brain tumors

Intravenous Infusion of Nucleated Peripheral Blood Cells Restores Fertility in Mice with Chemotherapy-Induced Premature Ovarian Failure

Cancer treatment with specific chemotherapeutic agents has been well documented to have an adverse impact on female fertility leading to premature ovarian failure (POF). The objective of this study is to investigate if chemotherapeutic induced POF can be reversed by the infusion of autologous nucleated peripheral blood cells (PBMC). To reach our goal, mice were treated with a single intraperitoneal injections of busulfan and cyclophosphamide to induce POF. This was followed by transfusion of PBMC. The ovarian morphology and functional parameters were monitored by radioimmunoassay, real-time PCR, immunofluorescence and immunohistochemistry analysis. Our study showed that chemotherapy (CTX) protracted estrous cycle period and repressed E2 production. In addition, CTX decreased the expressions of steroidogenesis markers, CYP-17 synthesis, StAR (steroidogenic acute regulatory protein), and Connexin-43 protein expression in the ovarian follicles. We also observed reduced numbers and sizes of the primordial and primary follicles in CTX-treated mice compared to untreated controls (p &lt; 0.05). When both CTX and untreated control groups were stimulated with gonadotrophin, the control group produced ten times more ova than the CTX group. Finally, the treatment of premature ovarian failure induced by CTX with autologous PBMC transfusion resulted in over-expression and a statistically significant increase in several stem cell markers and restoration of fertility. Infusion with PBMC in CTX further decreased the estrous cycle length by 2.5 times (p &lt; 0.01). We found that transfusion of autologous PBMC to mice with chemotherapy induced POF was very effective at restoring fertility. These results are similar to other studies using bone marrow derived mesenchymal stem cells

The Role of Gene Therapy in Premature Ovarian Insufficiency Management

Premature ovarian insufficiency (POI) is a highly prevalent disorder, characterized by the development of menopause before the age of 40. Most cases are idiopathic; however, in some women the cause of this condition (e.g.; anticancer treatment, genetic disorders, and enzymatic defects) could be identified. Although hormone-replacement therapy, the principal therapeutic approach for POI, helps alleviate the related symptoms, this does not effectively solve the issue of fertility. Assisted reproductive techniques also lack efficacy in these women. Thus, an effective approach to manage patients with POI is highly warranted. Several mechanisms associated with POI have been identified, including the lack of function of the follicle-stimulating hormone (FSH) receptor, alterations in apoptosis control, mutations in Sal-like 4 genes, and thymulin or basonuclin-1 deficiency. The above mentioned may be good targets for gene therapy in order to correct defects leading to POI. The goal of this review is to summarize current experiences on POI studies that employed gene therapy, and to discuss possible future directions in this field

Algebraické aspekty fuzzy logiky

In this thesis we study filters on algebras of fuzzy logics and their possible applications. We are going to generalize the notion of an implicative/ positive implicative/fantastic filter on BL-algebras by introducing a notion of R-S-filter. We state and prove some properties of R-S-filters and then we show the connection between characterization of R-S-filter and alternative axiomatization of a given logic. We are going to describe the way how to characterize given algebra of implicative logic via R-S-filters. We show that the results published in [1] and [3] are simple consequences of our theory. Next topics of this work are uniform spaces and uniform topologies. Filters are there used to set up so-called Leibnitz congruences. A set of this congruences on the algebra is a (sub)base of a uniformity that we are going to study. We are going to show that results published in [2] and [4] can be easily generalized for any implicative logics

NK cells confer protection against IOE-mediated immunopathology during recall response.

<p>Compared with naïve mice <b>(A),</b> and IOE-infected/unprimed mice <b>(B),</b> the livers of NK^+/+EM/IOE mice <b>(C)</b> have minimal apoptotic and necrotic cells but contain lymphohistiocytic cellular infiltration (arrowhead and inset) and minimal apoptosis. In contrast, the livers of NK^-/-EM/IOE-infected mice <b>(D)</b> has a greater number of apoptotic cells and foci of liver necrosis (arrows), as detected by H&E staining after challenge with IOE. (Original magnification, X40). Data are representative of sections from one mouse in each group with similar results obtained in three independent experiments with three mice per group.</p

NK cell depletion in <i>E</i>. <i>muris-</i>primed mice decreases expansion of memory T cells.

<p>Splenocytes from different groups of mice were stimulated with <i>E</i>. <i>muris</i> antigens and the frequency of memory cells was determined by flow cytometry. Lower percentages <b>(A)</b> and absolute numbers <b>(B)</b> of effector/effector memory (Em) (CD44^high CD62L^low), but not central memory (Cm) (CD44^high CD62L^high), CD4⁺ T cells in the spleens of NK^-/-<i>E</i>. <i>muris</i> compared with those found in NK^+/+<i>E</i>. <i>muris</i> or naïve mice infected with IOE on day 28 post-infection. ** indicate <i>P</i> < 0.01. Data are presented as the means ± SD of four mice per group from two independent experiments. ** indicates <i>P</i> <0.01.</p