No description available.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine in the branch of Obstetrics and Gynaecology. Johannesburg, 2017 / Background Recurrent IVF failures may result from implantation defects of which a thin endometrium is often implicated. Studies show that improved endometrial thickness increases the probability of successful IVF. Objectives To evaluate the effects of transcervical instillation of G-CSF as an adjunct to IVF. The study looked at the influence of G-CSF on the endometrium and on the achievement of pregnancy. Methods A retrospective cross-sectional study of women attending Bio ART Fertility Centre, who had two or more failed IVFs previously. Results There were a total of 49 women studied with a mean age of 38.9. Mean number of previous IVFs were 3.1. Comparison between those that achieved pregnancy and those that did not showed that age was a statistically significant factor (p-value 0.0005). Mean endometrial thickness pre and post-GCSF between the groups was not statistically significant (p-values >0.05). Conclusion With the use of G-CSF we achieved a clinical pregnancy rate of 34.69% and a statistically significant overall expansion of endometrial thickness (p-value 0.0029). However we failed to show any association between endometrial expansion and pregnancy outcome. / MT 2018

Pre-clinical studies suggest that granulocyte-colony stimulating factor (GCSF) holds promise for the treatment of ischaemic heart disease (IHD). However, its safety and efficacy in this setting, and in particular in patients with chronic refractory 'no-option' IHD, is unclear. Therefore, a clinical study was initiated in 20 such 'no-option' patients, with the aim of assessing the safety and efficacy of both G-CSF administration, and also, that of an intracoronary infusion of G-CSF mobilised CD133+ cells. The study involved initial baseline cardiac ischaemia assessment (symptom based questionnaire, exercise stress test (EST), nuclear Sestamibi (MIBI) and dobutamine stress echocardiographic (DSE) imaging). Stable 'no-option' IHD patients then received open-label G-CSF commencing at 10μg/kg s/c for five days, with an EST on days four and six (to facilitate myocardial cytokine generation and stem cell trafficking). After three months, cardiac ischaemia assessment and the same regimen of G-CSF and ESTs were repeated, but in addition, leukapheresis and then a randomised double-blinded intracoronary infusion of CD133+ or unselected cells were performed. Final cardiac ischaemia assessment was three months thereafter. Eighteen male and two female subjects (mean age 62.4) were enrolled. Eight events occurred that fulfilled pre-specified 'adverse event' criteria: four ischaemic (troponin positive) episodes, two episodes of transient thrombocytopaenia (one profound), one episode of gout and one unscheduled hospitalisation for exhaustion. Troponin was positive on 17 further occasions (all CK-MB negative), however, at these instances angina severity was identical to baseline. Importantly, no adverse event(s) resulted in any detectable long-term adverse sequelae for any subject. From baseline to final follow-up, the administration of two cycles of G-CSF was associated with statistically significant improvements in a range of subjective outcomes, including anginal symptoms, quality of life and EST performance (all p < 0.005). However, the objective MIBI and DSE scans showed only trends towards improvement (all p > 0.1). Compared to unselected cells, an intracoronary infusion of CD133+ cells did not improve either subjective or objective outcomes. In conclusion, administering G-CSF to patients with refractory 'no-option' IHD warrants careful monitoring, but may be performed with safety. A larger, randomised double-blind placebo-controlled trial of G-CSF in these patients appears warranted.

Pre-clinical studies suggest that granulocyte-colony stimulating factor (GCSF) holds promise for the treatment of ischaemic heart disease (IHD). However, its safety and efficacy in this setting, and in particular in patients with chronic refractory 'no-option' IHD, is unclear. Therefore, a clinical study was initiated in 20 such 'no-option' patients, with the aim of assessing the safety and efficacy of both G-CSF administration, and also, that of an intracoronary infusion of G-CSF mobilised CD133+ cells. The study involved initial baseline cardiac ischaemia assessment (symptom based questionnaire, exercise stress test (EST), nuclear Sestamibi (MIBI) and dobutamine stress echocardiographic (DSE) imaging). Stable 'no-option' IHD patients then received open-label G-CSF commencing at 10μg/kg s/c for five days, with an EST on days four and six (to facilitate myocardial cytokine generation and stem cell trafficking). After three months, cardiac ischaemia assessment and the same regimen of G-CSF and ESTs were repeated, but in addition, leukapheresis and then a randomised double-blinded intracoronary infusion of CD133+ or unselected cells were performed. Final cardiac ischaemia assessment was three months thereafter. Eighteen male and two female subjects (mean age 62.4) were enrolled. Eight events occurred that fulfilled pre-specified 'adverse event' criteria: four ischaemic (troponin positive) episodes, two episodes of transient thrombocytopaenia (one profound), one episode of gout and one unscheduled hospitalisation for exhaustion. Troponin was positive on 17 further occasions (all CK-MB negative), however, at these instances angina severity was identical to baseline. Importantly, no adverse event(s) resulted in any detectable long-term adverse sequelae for any subject. From baseline to final follow-up, the administration of two cycles of G-CSF was associated with statistically significant improvements in a range of subjective outcomes, including anginal symptoms, quality of life and EST performance (all p < 0.005). However, the objective MIBI and DSE scans showed only trends towards improvement (all p > 0.1). Compared to unselected cells, an intracoronary infusion of CD133+ cells did not improve either subjective or objective outcomes. In conclusion, administering G-CSF to patients with refractory 'no-option' IHD warrants careful monitoring, but may be performed with safety. A larger, randomised double-blind placebo-controlled trial of G-CSF in these patients appears warranted.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Ischemic stroke is defined as a blockage or reduced flow of blood to select areas of brain tissue due to either plaque formation or buildup of blood clots in the small blood vessels. A characteristic of sickle cell anemic patients is the potential for them to experience a similar type of blockage due to the sticky nature of the sickled red blood cells as well as defective oxygen delivery to the brain. Because of this similarity, sickle cell anemia may represent a good animal research model for therapeutic intervention based on stroke models. In recent studies, Granulocyte-Colony Stimulating Factor (GCSF), has been shown to exhibit a robust range of neuroprotective properties against neurological disorders including ischemic stroke through preservation of the endoplasmic reticulum (ER) by modulating various ER stress pathways. Through cognitive deficit analysis in the form of behavioral and locomotor experiments in addition to in situ biomarker analysis by way of western blotting and immunohistochemistry, we found that G-CSF gene therapy exhibited neurogenic and neuroprotective effects in ischemic mouse models and could possibly serve as a good therapy for other diseases that share similar pathology to stroke. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2021. / FAU Electronic Theses and Dissertations Collection

Thesis (Ph.D.). / Written for the Dept. of Mathematics and Statistics. Title from title page of PDF (viewed 2008/01/12). Includes bibliographical references.

G-CSF besitzt direkte Effekte auf die Aktivierung bakterizider Eigenschaften neutrophiler Granulozyten und verbessert das Überleben bakteriell infizierter Tiere. Daher wurde in der hier vorliegenden Arbeit der Effekt einer prophylaktischen oder therapeutischen Gabe von G-CSF bei experimenteller Pneumonie durch Klebsiella pneumoniae in Mäusen untersucht. Unerwarteterweise verschlechterte aber eine prophylaktische G-CSF-Gabe das Überleben und führte dosisabhängig zu einer Steigerung der bakteriellen Dissemination von der Lunge in Leber und Milz. Im Gegensatz dazu konnte ein spezifisch gegen K2-Kapselpolysaccharid (K2-KPS) von K. pneumoniae gerichteter monoklonaler Antikörper signifikant die Vermehrung der Bakterien in Lunge, Leber und Milz reduzieren. Die Blockierung von TNF?? durch Pentoxifyllin hingegen verzögerte die Letalität nach Induktion der Pneumonie, verhinderte sie jedoch nicht. In vitro konnte hier nachgewiesen werden, daß G-CSF spezifisch an K. pneumoniae bindet und daß diese Bindung an mehrere Proteine mit einem Molekulargewicht von 41, 25 und 21 kDa erfolgt. Die Bindung von G-CSF an K. pneumoniae führte zu einer signifikant erhöhten Produktion des wichtigsten Virulenzfaktors, K2-KPS. Dies verminderte in vitro signifikant eine Phagozytose der Bakterien durch neutrophile Granulozyten. Damit gelang es zum ersten Mal, die Bindung von G-CSF an ein gram-negatives Bakterium, K. pneumoniae, nachzuweisen und zu zeigen, daß diese Bindung in vitro zu einer erhöhten Produktion des wichtigsten Virulenzfaktors und in vivo zur Verschlechterung einer experimentellen Pneumonie durch erhöhte bakterielle Disseminierung bei prophylaktischer Gabe von G-CSF vor Infektion führt. Die weitere Untersuchung dieser Phänomene hinsichtlich einer möglichen Bindung von G-CSF auch an andere Bakterien könnte zu einer differenzierten supportiven Therapie bakterieller Infektionen mit G-CSF in nicht neutropenischen Patienten führen. / Besides its well-established effects on granulocytopoiesis, granulocyte colony-stimulating factor (G-CSF) has been shown to have direct effects on the recruitment and bactericidal ability of neutrophils, resulting in improved survival of experimentally infected animals. The effect of G-CSF on the course of experimental pneumonia induced by Klebsiella pneumoniae was studied. Using a highly reproducible murine model, the paradoxical finding that mortality from infection was significantly increased when animals received G-CSF before induction of pneumonia could be demonstrated. Administration of G-CSF promoted replication of bacteria in the liver and spleen, thus indicating an impairment rather than an enhancement of antibacterial mechanisms. By contrast, a monoclonal antibody against Klebsiella K2 capsule significantly reduced bacterial multiplication in the lung, liver, and spleen, and abrogated the increased mortality caused by G-CSF. Blocking of TNF-? with pentoxifylline, however, could not prevent increased mortality caused by G-CSF. In vitro studies showed a direct effect of G-CSF on K pneumoniae resulting in inreased capsular polysaccharide (CPS) production. When bacteria were coincubated with therapeutically achievable concentrations of G-CSF, phagocytic uptake and killing by neutrophils was impaired. Western blot analysis showed three binding sites of G-CSF to K pneumoniae. Thus, in this model, the direct effect of G-CSF on a bacterial virulence factor, CPS production, outweighed any beneficial effect of G-CSF on recruitment and stimulation of leukocytes. Further investigations of possible binding of G-CSF to other bacteria might influence a differentiated supportive therapy of bacterial infections in non-neutropenic patients with this growth factor.

Les cellules Natural Killer (NK) sont capables de lyser les cellules tumorales sans la nécessité de reconnaitre un antigène tumoral spécifique. Cette propriété leur confère un avantage par rapport aux lymphocytes T et les rend intéressantes à utiliser en tant que cellules effectrices pour l’immunothérapie adoptive. A ce jour, le potentiel thérapeutique des cellules NK n’a pas été complétement exploré notamment dans le contexte du traitement de la rechute post-allogreffe de cellules souches hématopoïétiques. Actuellement, les patients en rechute post-greffe sont traités avec des injections de lymphocytes du donneur (DLI) parfois issues de petites fractions du greffon de cellules souches hématopoïétiques congelées. Les cellules souches périphériques étant fréquemment utilisées comme source de cellules souches et parfois utilisées comme DLI, nous avons souhaité évaluer l’impact du G-CSF sur le phénotype et les fonctions des cellules NK présentes dans ces fractions. Dans cet objectif, nous avons comparé différentes sources de cellules NK isolées à partir de sang de donneurs sains, de sang mobilisé de donneurs sains ou de patients et observé l’évolution des différentes sous-populations de cellules NK issues de ces prélèvements au décours d’une expansion en présence d’IL-15. Nos résultats ont montré que l’administration de G-CSF diminuait la proportion de cellules NK CD56brightCD16+ au profit d’une population CD16-, diminuait la prolifération des cellules NK lors de l’expansion en culture, et modifiait les propriétés fonctionnelles des cellules NK. / The ability of natural killer (NK) cells to kill tumor cells without the need to recognize a tumor-specific antigen provides advantages over T cells and makes them appealing for a use as effectors for adoptive immunotherapy. However, the full therapeutic potential of NK cell-based immunotherapy has not been fully investigated in the context of leukemic relapse after hematopoietic stem cell transplantation. Today, patients relapsing after hematopoietic stem cell transplantation are often treated with donor lymphocyte infusion (DLI) based on small cell fractions frozen at the time of the stem cell transplantation. Since peripheral blood stem cells are increasingly used as stem cell source and as source of cells for DLI, we aimed to evaluate the impact of G-SCF mobilization on NK cell phenotype and functions. Therefore, we compared the expansion capacity, the phenotype and the function of NK cells from blood for healthy donors, from allogeneic HSCT healthy donors or from autologous HSCT from patients. We also determine the impact of G-CSF on NK cell subset repartition before and after expansion in presence of IL-15. Our results showed that G-CSF administration to patients decreases CD56brightCD16+ NK cell population, proliferation and function. Overcoming this impairment in lymphoid capacity may be important to facilitate post-transplant immunotherapy.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.