94 results on '"Rožman, Primož"'
Search Results
52. Reliable Determination of Fetal RhD Status by RHD Genotyping from Maternal Plasma
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Dovč-Drnovšek, Tadeja, Klemenc, Polona, Toplak, Nataša, Blejec, Tanja, Bricl, Irena, and Rožman, Primož
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Original Article - Abstract
Immunoprophylaxis with IgG anti-D is a standard prevention of hemolytic disease of the fetus and newborn. Fetal Rhesus D (RhD) blood group genotyping from maternal plasma of RhD-negative pregnant women allows targeted prophylaxis with IgG anti-D in RhD-positive pregnancies only. We set up a reliable protocol for prenatal RHD genotyping.153 pregnant Caucasian RhD-negative women were tested in the 27th week (range 7-38th week) of pregnancy. 18 of them were alloimmunized to the RhD antigen. The fetal RHD genotype was determined based on an automated DNA extraction and real-time polymerase chain reaction method. Intron 4 and exons 5, 7 and 10 of the RHD gene and the SRY gene were targeted.The fetal RhD status and gender was 100% correctly predicted in all 153 pregnancies (55 RhD-positive males, 45 RhD-positive females; 23 RhD-negative males, 30 RhD-negative females).The accuracy and applicability of our protocol for non-invasive fetal RhD determination allows the correct management of RhD-incompatible pregnancies. Our protocol could prevent unnecessary immunoprophylaxis in 53 of 153 cases. We therefore recommend that non-invasive fetal RHD genotyping is introduced as an obligatory part of prenatal screening.
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- 2013
53. REGENERATION OF CHRONIC WOUNDS WITH ALLOGENEIC PLATELET GEL VERSUS HYDROGEL TREATMENT: A PROSPECTIVE STUDY.
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Semenič, Danijela, Cirman, Tina, Rožman, Primož, and Smrke, Dragica Maja
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- 2018
- Full Text
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54. Serološke in funkcijske preiskave pri diagnosticiranju trombocitopenije, povzročene s heparinom (HIT): Serological and functional tests for the diagnosis of heparin-induced thrombocytopenia
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Dovč, Tadeja, Maličev, Elvira, and Rožman, Primož
- Abstract
Heparin-induced thrombocytopenia (HIT) is an immune-mediated reaction occurring in 3 - 5 % of patients receiving heparin therapy for more than 5 days, which can lead to arterial and venous thrombosis. It is caused by IgG antibodies directed against platelet factor 4/heparin complexes, leading to platelet activation, platelet depletion and thrombocytopenia. Prolonged therapy with heparin can result in serious adverse consequences, so prompt diagnosis is of key importance for the introduction of supplemental therapy. The diagnosis of HIT is based on clinical criteria as well as on serological and functional laboratory assays. Serological assays that identify the presence of platelet factor 4/heparin antibodies in the serum are not sufficient for confirmation of diagnosis because all detected antibodies are not capable of causing thrombocytopenia and thrombosis. Since the usual enzyme-immune assays detect the presence of antibodies but not also their pathogeneity it is recommended to confirm HIT with a functional assay that confirms the capacity of HIT antibodies to activate or aggregate platelets. One of newer functional methods is the flow cytometric analysis of P-selectin (CD62P) expression on the standard platelets after exposure to the patientćs serum. In our experience, this test, in parallele with standard serological tests, proved its reliability for the confirmation of clinical HIT diagnosis.
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- 2012
55. Preventiva in diagnostika hemolitične bolezni ploda in novorojenčka: Prevention and diagnostics of haemolytic disease of the fetus and newborn
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Bricl, Irena, Dovč, Tadeja, Rožman, Primož, and Železnik, Klara
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- 2012
56. Pluripotentne matične celice v embrionalnem razvoju in pri odraslem: Pluripotent stem cells during embryo development and in the adult
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Jež, Mojca, Rožman, Primož, and Veber, Matija
- Abstract
According to their capabilities for differentiation stem cells can be totipotent, pluripotent, multipotent and unipotent. After fertilization, zygote is the ultimate totipotent cell. Cells arising durring embryonic development have a lesser potency. Different pluripotent cell types are known: embryonic stem cells, embryonic germ cells, induced pluripotent stem cells, epiblast stem cells, and still controversial pluripotent stem cells isolated from the adult tissues. It is currently recognized that every tissue contains a small population of stem cells that are capable of self-renewal and differentiation. Embryonic stem cells have the broadest potential for differentiation because they are capable of turning into every cell type in our bodies. This is the reason why they are the most interesting for use in medicine. Lately, a lot of new studies have shown that somatic stem cells have broader potency than it has been expected until now and at the same time do not have any of embryonic stem cell drawbacks.
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- 2012
57. Shranjevanje matičnih celic iz popkovnične krvi - danes in jutri: Umbilical cord blood banking - today and tomorrow
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Domanovič, Dragoslav, Knežević, Miomir, and Rožman, Primož
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fluids and secretions ,embryonic structures - Abstract
Umbilical cord blood (UCB) is an abundant source of haematopoietic stem cells (HSC) for allogeneic HSC transplant. In addition to HSCs, the cord blood and placenta contain ample nonhaematopoietic stem cells, which increasingly raise the interest of regenerative medicine. Public UCB banks have more than 500.000UCB units in international UCB registries that are available for the international exchange. It is estimated that additional two-fold number of units are held in the private UCB banks that store the cells for autologous purposes. Although the development of hybrid UCB banks was predicted in which the private units of UCB could be used for allogeneic purposes if needed, thishas not yet happened. The activity of UCB registries is complementary to the bone marrow donor registries, which keep the data of more than 16 million donors. The key data for international exchange of UCB are the HLA typing results and the stem cell count in the UCB units. The majority of international associations and bodies do not support the autologous UCB banking based on the current poor evidence on the usefulness of autologous UCBcells. However, this opinion is changing owing to the development of regenerative medicine so changes of the ethical and expert opinions are expected. In Slovenia, the only public UCB bank is maintained at the Blood Transfusion Centre of Slovenia, whereas the only private UCB bank is Biobanka.Since unlimited expansion in the number of UCB units does not increase the like-lihood of finding HLA-identical grafts, in Slovenia we plan to collect maximum up to 2000 UCB units. In order to foster the solidarity andequal accessibility, one needs to assure the use of UCB derived cells for children and adults for their possible treatment in the future.
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- 2012
58. Presaditve matičnih celic iz popkovnične krvi - dve desetletji kliničnih izkušenj: Umbilical cord stem cell transplantation - two decades of clinical experience
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Domanovič, Dragoslav, Jazbec, Janez, and Rožman, Primož
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fluids and secretions ,embryonic structures - Abstract
Umbilical cord blood (UCB) is an abundant source of haematopoietic stem cells (HSC) for allogeneic HSC transplant. Since the first UCB transplant in 1988, many scientific data have been collected. Many umbilical cord blood banks havebeen established worldwide for the collection and cryopreservation as wellas for the international exchange with more than 400,000 UC units available. There is probably a twofold figure of UCB units collected for the private UCB banks. More than 20,000 UCB units have been used for treating malignant and non-malignant diseases both in adults and children. Unrelated UCB HSCs became an alternative to bone-marrow derived HSCs based on their advantages, including a prompt availability, decrease of graftversus- host disease (GVHD) and better longterm immune recovery, resulting in a similar long-term survival. UCB stem cells can be transplanted to an allogeneic patient in spite of the high degree of HLA mismatches, which is highly important for the patients who cannot find a HLA-identical allogeneic donor. Since the low number of cells in the UCB units still represents the main causeof failure of engraftment, new strategies, such as double-unit UCB transplantation, intra-bone injection of UCB cells, simultaneous transplantation of accessory cells and the reduced intensity conditioning regimen, were developed to increase the success of UCB transplantation. Several clinical studies using UCB stem cells that have been previously expanded in vitro are underway. These procedures and the future development ofregenerative medicine will further broaden possible indications for the use of UCB derived stem cells in adults.
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- 2012
59. Zdravljenje z matičnimi celicami: Stem cell therapy
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Jež, Mojca, Rožman, Primož, Strbad, Marko, and Šimc, Mojca
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Despite the progress in medicine, we are nowadays still faced with diseases and injuries, where with the knowledge, drugs and support technology availableto us, we cannot achieve the desired quality of patientćs life. Progress in stem cell biology may be the hope for certain diseases in the future. The purpose of this article is to present a rapidly advancing field ofstem cells. We summarize the properties of stem cells, various types of stemcells according to their origin from the embryonic or adult tissues, and according to their differentiation potential. Although numerous factors that determine the properties of stem cells are currently already known, we still need to know more about their mutual impact. We present the fields of clinicalmedicine where stem cells are already used for treatment, as well as those, for which there is, a justified hope that stem cell therapy will becomepart of routine treatment in the near future. The greatest potential of stem cells is probably their use in the treatment of degenerative diseases andtraumatic injuries, where we expect a major impact on the patientćs qualityof life. Similarly, the knowledge of stem cells has also contributed tounderstanding cancer diseases and thus open up opportunities for new approach to treating these diseases.
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- 2012
60. The Role of Platelet Gel in Regenerative Medicine
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Rožman, Primož
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Technology & Engineering / Biomedical - Abstract
The Role of Platelet Gel in Regenerative Medicine
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- 2011
61. Concise Review: The Role of Oxygen in Hematopoietic Stem Cell Physiology
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Jež, Mojca, primary, Rožman, Primož, additional, Ivanović, Zoran, additional, and Bas, Tuba, additional
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- 2015
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62. Analysis of Glioblastoma Patients' Plasma Revealed the Presence of MicroRNAs with a Prognostic Impact on Survival and Those of Viral Origin
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Herman, Ana, primary, Gruden, Kristina, additional, Blejec, Andrej, additional, Podpečan, Vid, additional, Motaln, Helena, additional, Rožman, Primož, additional, Hren, Matjaž, additional, Zupančič, Klemen, additional, Veber, Matija, additional, Verbovšek, Urška, additional, Lah Turnšek, Tamara, additional, Porčnik, Andrej, additional, Koršič, Marjan, additional, Knežević, Miomir, additional, and Jeras, Matjaž, additional
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- 2015
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63. Naturally occurring anti-E red-cell antibodies in a 3-month old infant: Naravna anti-E eritrocitna protitelesa prisotna pri trimesečnem otroku
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Rožman, Primož and Šimc, Mojca
- Abstract
Background: Before the transfusion of the red blood cells containing blood components is applied, pre-transfusion testing such as ABO, RhD and Kell bloodgrouping with a negative crossmatch is obligatory. This can be reduced toblood grouping only in infants less than 4 months of age, provided that the initial antibody screening test is negative. Only a few cases of antibody formation in such young infants have been described, the majority of them haveresulted from exposure to allogeneic transfusions. Case report: During thepre-transfusion testing, naturally occurring anti-E red blood cell antibodies were detected in a 3-month old male infant, who underwent surgery for atresia of the extra hepatic bile ducts followed by a bacterial infection.All immunohaematological tests were performed using the commercial gel column agglutination method, screening cells, RBC panel and enzyme-modified cells according to the manufacturerćs instructions. The passive transfer of anti-E antibodies with blood components and the transfer of the antibodies from the mother during pregnancy and also through lactation were excluded. Immunisation due to exposure to E antigen was ruled out by confirming the E-negativity of all the red blood cell units the infant had received and also by confirming the E-negativity of the mother. Conclusion: Although the naturally occurring anti-E red-cell antibodies are usually found in adults, we report here a case of a 3-month old infant, who had developed naturally occurring anti-E red cell antibodies.
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- 2010
64. Uvedba telekonzultacij v transfuzijsko službo: Introduction of teleconsultations in the blood transfusion service
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Breskvar, Marko, Bricl, Irena, Meža, Marko, Rožman, Primož, and Tasič, Jurij F.
- Abstract
Background By introducing telemedicine, we would like to provide support for anew organization of the Slovenian transfusion service to ensure a uniform quality of services throughout the country. We would like to increase safety and to enable professional consultations by means of modern technology during periods when no transfusion medicine specialist is present at the transfusion departments. Methods A system that enables teleconsultations between individual transfusion institutions requires a safe and coded network, equipment for the capturing and processing of multimedia data, a videoconferencing system, and links to individual professional environments. An apparatus (Gelscope) has been developed to capture and process digitized images of laboratory data obtained by testing according to the gel method. Teleconsultations are performed as special scenarios which essentially includes questions passed by the on-duty doctor and qualified replies of the transfusion medicine specialist that are sent from the consultation center. Results An effective transfusion service requires the provision of uninterrupted on-duty coverage (24 hours/7 days) for each transfusion institution. Through the use of a teleconsultation system, it is possible to reduce the number of on-duty transfusion specialists from 11 to only 2. Furthermore, the system ensures a uniform quality of transfusion services overthe entire country. Validation of the pilot system has been completed and its results have shown that a transfusionćs services provided on a remote basis are equivalent in quality. Conclusions The teleconsultation system enables professional consultations via the use of modern technology. The implementation of this system will be continued and expanded from the current 4 system in use to 11 throughout Slovenia. The computer application is modularand it should also be suitable for use in other areas of medicine, suchas emergency medicine, etc.
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- 2008
65. Use of platelet growth factors in treating wounds and soft-tissue injuries
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Bolta, Zoran and Rožman, Primož
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Tissue repair begins with clot formation and platelet degranulation, which release the growth factors (GFs) necessary for wound repair. Platelet-derived GFs are biologically active substances that enhance tissue repair mechanisms such as chemotaxis, cell proliferation, angiogenesis, extracellular matrix deposition, and remodeling. This review describes the biological background ofthe topical therapy of wounds and soft-tissue injuries with platelet gel (PG) and PG-derived GFs as well as the success of the clinical studies performed so far. Some other interesting topical applications of PG are also described. Platelet-derivatives represent a promising therapeutic modality, offering opportunities for treatment of wounds, ulcers, soft-tissue injuries,and various other applications in regenerative medicine.
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- 2007
66. An uncommon treatment of totally extruded and lost talus: a case report
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Smrke, Dragica Maja, primary, Rožman, Primož, additional, Gubina, Borut, additional, Frangež, Igor, additional, Smrke, Barbara Rejec, additional, and Arnež, Zoran Marij, additional
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- 2014
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67. Amniotic membrane properties and current practice of amniotic membrane use in ophthalmology in Slovenia
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Cirman, Tina, primary, Beltram, Matej, additional, Schollmayer, Petra, additional, Rožman, Primož, additional, and Kreft, Mateja Erdani, additional
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- 2013
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68. Tolerogenic dendritic cells: molecular and cellular mechanisms in transplantation
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Švajger, Urban, primary and Rožman, Primož, additional
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- 2013
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69. Preventivni ukrepi za izboljšanje varnosti transfuzije in virtualni transfuzijski laboratorij: Preventive measures for the improvement of the safety of blood transfusion andvirtual transfusion laboratory
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Rožman, Primož
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Background. Even though blood transfusion is a relatively safe form of therapy, because of the eventual administrative errors in the transfusion chain between the blood donor and the recipient of blood, transfusion errors still occur. Therefore, it is imperative to ensure an utmost extent of safety and reliability of all transfusion related procedures. The safety of blood transfusion can be improved by preventive actions, i.e. implementation of the total quality management concept, haemovigilance and virtual transfusion laboratory. In the resulting system, the information web, robotics, computer sciences and communication technologies ensuresafe and reliable identificationof the patients, blood donors, corresponding test samples and blood products. Apart form this; the modern technologies enable the automationof laboratory testing, the integrity of laboratory results and enable an optimal use of blood. Conclusions. For an improved transfusion safety in Slovenia, adoption of corresponding prevention as well as haemovigilance is necessary. Identification errors can be prevented by implementation of the wrist bands systems with the code bars for the tagging of the patient and his biological samples, whereas the administrative errors in the blood bank and transfusion laboratory can be prevented by implementation of information systems and automation. We assume that the virtual transfusion laboratory will become an integral part of the new Slovenian transfusion web and will speed up, unify and simplify today's methods of ordering and administering blood products. (Abstract truncated at 2000 characters). Izhodišča. Kljub temu da je transfuzija relativno varna oblika zdravljenja, zaradi možnih administrativnih napak v transfuzijski verigi med krvodajalcem in bolnikom še vedno lahko prihaja do napak. Zato je treba zagotoviti čim večjo varnost in zanesljivost vseh postopkov v zvezi s transfuzijo krvi. Varnost transfuzije lahko povečamo predvsem s preventivnimi ukrepi, to je z uvedbo celostnega sistema kakovosti, sistema hemovigilance in z virtualnim transfuzijskim laboratorijem. V takem sistemu informacijska mreža, robotika, računalništvo in komunikacijske tehnologije zagotovijo zanesljivost identifikacije bolnika-prejemnika krvi, dajalca krvi, ustreznih vzorcev krvi in izdelanih krvnih pripravkov. Sodobne tehnologije omogočajo poleg omenjenegatudi avtomatizacijo laboratorijskega testiranja, zagotavljajo integriteto laboratorijskih izsledkov in omogočajo smotrnejšo izrabo krvi. Zaključki. Za večjo transfuzijsko varnost moramo s preventivnimi ukrepi in uvedbo hemovigilance nujno poskrbeti tudi v Sloveniji. Napake pri identifikaciji bolnika lahko preprečimo s sistemom zapestnic s črtno kodo za označitev bolnika in njegovih bioloških vzorcev administrativne napake v krvnibanki in laboratoriju pa z informacijskim sistemom in avtomatizacijo. Predvidevamo, da bo virtualni transfuzijski laboratorij postal sestavni del nove enotne slovenske transfuzijske mreže, ki bo pospešila, poenotila in poenostavila sedanje postopke v zvezi z naročanjem in aplikacijo krvnih pripravkov odgovornemu zdravniku bo omogočila izbrati optimalno shemo transfuzije, obenem pa bo omogočila spremljanje individualnih naročanj, odstopanj indikacij in diagnoz, kar je potrebno za analizo in izboljšavo kakovosti ter za analizo stroškov zdravjenja. Ti ukrepi predstavljajo tudi prvi nujni korak v posodobitvi transfuzijske medicine in s tem tudi slovenskega zdravstva v smislu zagotavljanja celostne kakovosti.
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- 2002
70. Reliable Determination of Fetal RhD Status by RHD Genotyping from Maternal Plasma
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Dovč-Drnovšek, Tadeja, primary, Klemenc, Polona, additional, Toplak, Nataša, additional, Blejec, Tanja, additional, Bricl, Irena, additional, and Rožman, Primož, additional
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- 2013
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71. The hazards of DAPI photoconversion: effects of dye, mounting media and fixative, and how to minimize the problem
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Jež, Mojca, primary, Bas, Tuba, additional, Veber, Matija, additional, Košir, Andrej, additional, Dominko, Tanja, additional, Page, Raymond, additional, and Rožman, Primož, additional
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- 2012
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72. A “Crossomics” Study Analysing Variability of Different Components in Peripheral Blood of Healthy Caucasoid Individuals
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Gruden, Kristina, primary, Hren, Matjaž, additional, Herman, Ana, additional, Blejec, Andrej, additional, Albrecht, Tanja, additional, Selbig, Joachim, additional, Bauer, Chris, additional, Schuchardt, Johannes, additional, Or-Guil, Michal, additional, Zupančič, Klemen, additional, Švajger, Urban, additional, Štabuc, Borut, additional, Ihan, Alojz, additional, Kopitar, Andreja Nataša, additional, Ravnikar, Maja, additional, Knežević, Miomir, additional, Rožman, Primož, additional, and Jeras, Matjaž, additional
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- 2012
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73. Parthenogenetic Embryo-Like Structures in the Human Ovarian Surface Epithelium Cell Culture in Postmenopausal Women with No Naturally Present Follicles and Oocytes
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Virant-Klun, Irma, primary, Rožman, Primož, additional, Cvjeticanin, Branko, additional, Vrtacnik-Bokal, Eda, additional, Novakovic, Srdjan, additional, Rülicke, Thomas, additional, Dovc, Peter, additional, and Meden-Vrtovec, Helena, additional
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- 2009
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74. Telemedicine in the blood transfusion laboratory – remote interpretation of pre-transfusion tests
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Meža, Marko, primary, Breskvar, Marko, additional, Košir, Andrej, additional, Bricl, Irena, additional, Tasič, Jurij, additional, and Rožman, Primož, additional
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- 2007
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75. Allogeneic Platelet Gel with Autologous Cancellous Bone Graft for the Treatment of a Large Bone Defect
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Smrke, Dragica, primary, Gubina, Borut, additional, Domanoviç, Dragoslav, additional, and Rožman, Primož, additional
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- 2007
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76. New antagonists of toll-like receptor 7 discovered through 3D ligand-based virtual screening.
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Švajger, Urban, Horvat, Žiga, Knez, Damijan, Rožman, Primož, Turk, Samo, and Gobec, Stanislav
- Abstract
Toll-like receptor (TLR) 7 has an important role in immune activation processes and represents an emerging drug discovery target for the development of immunomodulators. Three-dimensional similarity-based virtual screening was performed using the Rapid Overlay of Chemical Structures software (vROCS version 3.1.1. OpenEye Scientific Software, Santa Fe, NM. ) to search for potential ligands of TLR7. Six new compounds with three new chemical scaffolds were discovered as initial hit antagonists of TLR7, with IC values in the micromolar range, as determined by reporter assays. With only the imidazoquinolines described as small-molecule TLR7 antagonists to date, the new chemotypes described in this report represent an important starting point for the development of drug candidates for treatment of autoimmune diseases. [ABSTRACT FROM AUTHOR]
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- 2015
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77. Transfusion Medicine in Slovenia – Current Status and Future Challenges
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Rožman, Primož, primary and Domanović, Dragoslav, additional
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- 2006
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78. Is the ABO incompatibility a risk factor in bone marrow transplantation?
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Rožman, Primož, primary, Košir, Andrej, additional, and Bohinjec, Mateja, additional
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- 2005
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79. Editorial
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Bohinjec, Mateja, primary and Rožman, Primož, additional
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- 2002
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80. The Influence of Allogeneic Platelet Gel on the Morphology of Human Long Bones.
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Gubina, Borut, Rožman, Primož, Bišćević, Mirza, Domanović, Dragoslav, and Smrke, Dragica
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BONE grafting ,CANCELLOUS bone ,AUTOGRAFTS ,BLOOD platelets ,BONES ,PSEUDARTHROSIS ,MORPHOLOGY ,ANATOMY - Abstract
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- 2014
81. Tolerogenic dendritic cells: molecular and cellular mechanisms in transplantation
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Švajger, Urban and Rožman, Primož
- Abstract
Review on the molecular and cellular mechanisms which guide immune tolerance associated with dendritic cells, with focus on transplantation setting. During the discovery of mechanisms that govern immune activation and suppression, immune tolerance always came second in the scientific timeline. This has subsequently shaped the advances in the clinical translation of DC therapy protocols used for immunostimulation or immunosuppression. With several hundred clinical trials already registered within the U.S. National Institutes of Health for the use of DCs in cancer vaccination, only a few involve TolDCs for use as negative vaccines. However, as a result of the strong scientific rationale from preclinical and clinical trials, the use of negative vaccination in organ transplantation is likely on its way to reach the extent of the use of positive cancer vaccines in the future. As the underlying mechanisms emerge, the role of DCs in the induction of transplant tolerance is recognized unambiguously as central in the bidirectional communication with various types of immune cells. This is achieved by a complex interplay of numerous tolerogenic signals involving regulatory cytokines and other surface‐bound or soluble inhibitory molecules associated with corresponding inhibitory signaling cascades. A detailed understanding of these processes will accelerate the advances of clinical immunologists in translating their knowledge from bench to bedside. In this review, we present the role of TolDCs as well as the most recent findings concerning associated molecular and cellular mechanisms that shape the balance between regulatory and effector immune responses during organ transplantation.
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- 2014
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82. Concerns About the Effects of Platelet Concentrate
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Vogrin, Matjaz, Rozman, Primoz, and Haspl, Miroslav
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- 2009
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83. Imunski sistem in dolgoživost mišjih samic BALB/c po presaditvi kostnega mozga mladih samcev
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Jazbec, Katerina and Rožman, Primož
- Subjects
mice ,presaditev kostnega mozga ,bone marrow transplantation ,staranje ,aging ,miši ,imunski sistem ,dolgoživost ,hematopoietic stem cells ,cell isolation ,longevity ,fraility index ,krvotvorne matične celice ,indeks krhkosti ,himerizem - Abstract
Starostne spremembe imunskega sistema so vzrok za zmanjšano sposobnost obrambe proti okužbam, za pojav vnetnih bolezni in povečano incidenco raka. Obstaja več teorij, ki skušajo razložiti številne istočasne in prepletene procese staranja. Po teoriji staranja matičnih celic je za staranje tkiv in organov odgovoren upad sposobnosti matičnih celic, da bi uspešno obnavljale tkiva. Namen naše raziskave je bil na modelu laboratorijskih miši raziskati, ali lahko presaditev celic kostnega mozga (KM) mladih živali izboljša delovanje imunskega sistema starih živali ter s tem izboljša njihovo splošno zdravje in morda celo podaljša življenjsko dobo. Neobsevanim samicam BALB/c smo v 14., 16. in 18. (19.) mesecu starosti presadili celice KM mladih samcev. Vsem prejemnicam celic KM smo določili stopnjo himerizma v KM, v izoliranih populacijah limfocitov T, limfocitov B in nevtrofilcev ter v CFU kolonijah, pripravljenih iz KM prejemnic. Analizirali smo spremembe števila celic prirojenega in pridobljenega imunskega sistema ter funkcij imunskih celic po presaditvi (sposobnost endocitoze, citokinski odziv in test stimulacije proliferacije). Manjše število živali smo imunizirali s hemocianinom iz školjke (KLH) ter z analizo titra protiteles testirali njihov imunski odziv na antigen. Pri vseh miših smo redno ocenjevali 30 različnih parametrov ter določili indeks krhkosti. Spremljali smo njihovo življenjsko dobo ter ob smrti opravili raztelesbe ter beležili patoanatomske spremembe. Rezultati so pokazali, da so imele stare miši, ki so prejele celice mladega KM, izboljšane nekatere imunske parametre prirojenega in pridobljenega imunskega sistema v primerjavi s kontrolno skupino, vendar teh ni bilo dovolj, da bi lahko hipotezo raziskave potrdili. Prejemnice KM niso imele vidno boljšega splošnega zdravja, indeks krhkosti ni pokazal razlik med poskusno in kontrolno skupino in miši tudi niso živele dlje od kontrolne skupine miši. Age-related changes in immune functions are the cause of the increased vulnerability to infections, inflammatory diseases, and cancer incidence. There are many existing theories that try to explain the numerous, simultaneous, and interconnected aging processes. The stem cell theory of aging postulates that stem cells become inefficient at maintaining the original functions of the tissues. In our study, we used a mice model to observe whether non-conditioned bone marrow (BM) cell transplantation from young donors to old recipients would improve their immune system functions, improve their general health, and possibly even extend their lifespans. Female BALB/c mice received BM cells from young donors at 14, 16 and 18(19) months of age. We determined chimerism levels in the BM, isolated T cell, B cell and neutrophil populations, and in colony-forming units (CFU) in BM. We analysed the changes of relative cell number of the innate and adaptive immune systems, and conducted functional assays (endocytic capability, cytokine response, and cell proliferation). We immunized a small group of mice with keyhole limpet haemocyanin (KLH) antigen and tested their immune response to antigen. All mice were regularly assessed using 30 parameters to calculate a frailty index (FI). We noted their lifespans, conducted post-mortem examinations, and recorded any pathoanatomical changes. Our results showed that old mice, transplanted with the BM cells of young donors, had some improvement in the immune parameters of their innate and adaptive systems, however, the evidence was insufficient for us to confirm our hypothesis. Recipient mice did not experience a noticeable improvement in their general health, and the FI showed no significant differences between the transplanted and control mice. In addition, the transplanted group did not live longer than the control group.
- Published
- 2021
84. Vpliv nemieloablativne presaditve mladih krvotvornih matičnih celic na imunske dejavnike starega prejemnika v mišjem modelu
- Author
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Justin, Mojca and Rožman, Primož
- Subjects
bone marrow ,staranje ,aging ,staranje imunskega sistema ,mišji modeli ,imunski sistem ,murine models ,CASIN ,dolgoživost ,presaditev krvotvornih matičnih celic ,immune system ,immune system aging ,chimerism ,longevity ,hematopoietic stem cell transplantation ,kostni mozeg ,himerizem - Abstract
Staranje je zapleten, več faktorski proces, ki prizadane celice, tkiva in organe. S staranjem organizma se stara tudi imunski sistem, ki je sicer ključen za obrambo organizma pred škodljivim okoljem. S starostjo povezane okvare imunskega sistema vodijo v nastanek večine s starostjo povezanih bolezni kot so rak, avtoimunske bolezni in srčno-žilne bolezni ter povročijo povečano dovzetnost posameznika za okužbe. Ena izmed možnih terapij, ki bi lahko izboljšala delovanje imunskega sistema v starosti, je presaditev mladih krvotvornih matičnih in progenitorskih celic (KMPC), ki bi jih posamezniku odvzeli in shranili v njegovi mladosti ter ponovno presadili v njegovi starosti. Sklepamo, da bi na ta način mlade in zdrave KMPC po presaditvi »pomladile« stari imunski sistem ter izboljšale njegovo delovanje, ob enem pa bi posamezniku podaljšali njegovo življensko dobo. Omenjeni princip se imunuje heterohrona avtologna presaditev mladih krvotvornih matičnih celic. V raziskavi smo v mišjem modelu uporabili nov način presaditve KMPC s predhodno mobilizacijo endogenih KMC v periferno kri. V ta namen smo uporabili molekulo CASIN, ki začasno izprazni nišo kostnega mozga prejemnika, na ta način pa omogoči večjemu številu presajenih celic pritrjanje vanjo. Z uporabo molekule CASIN smo po presaditvi mladih KMPC starim prejemnicam dosegli visok odstotek donorskega himerizma, dokazali nekatere izboljšave v imunskem sistemu in rahlo povišali mediano preživetja. Kljub temu pa bi bilo za prenos v humano medicino potrebno izvesti dodatne raziskave, ki bi potrdili ugodne učinke tovrstne terapije. Aging is a complex multi-factorial process that affects cells, tissues and organs. It also affects the immune system, which is crucial for the body's defense against the harmful environment. Age-related defects of the immune system lead to the development of most age-related diseases, such as cancer, autoimmune and cardiovascular diseases and cause an increased susceptibility to infections. One of the strategies that could improve the function of the immune system of an old individual is the transplantation of young hematopoietic stem and progenitor cells (HSCs) which would be collected from an individual in his/her youth and cryopreserved for a long time. After re-infusion later in life of the same individual, young and healthy HSPCs could »rejuvenate« the old immune system and improve its functioning. Furthermore, individuals lifespan could be prolonged. The process is called heterochronous autologous hematopoietic stem cell transplantation. In this study we used a new method of HSC transplantation with prior mobilization of endogenous HSCs into peripheral blood. For this purpose, we used the molecule CASIN, which temporarily empties the recipient's niche, thus allowing engraftment of a larger number of transplanted cells. With the use of the CASIN molecule, we achieved a high percentage of donor chimerism after transplantation of young HSPCs into old recipients. In the recipients of young HSPCs, we detected some improvements in the function of the immune system and a slighty higher median lifespan. Nevertheless, for translation into human medicine, additional research would be needed to confirm the beneficial effects of this type of therapy.
- Published
- 2021
85. Serijska presaditev kostnega mozga pri neobsevanih miših BALB/c
- Author
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Jazbec, Katerina and Rožman, Primož
- Subjects
bone marrow ,ugnezditev celic ,krvotvorne matične celice ,kostni mozeg ,udc:616.419(043.2) ,vsaditev celic ,homing ,engraftment ,hematopoietic stem cells - Published
- 2020
86. Sledenje uspešnosti alogenske presaditve krvotvornih matičnih celic na nivoju genomske DNA z metodo PCR v realnem času
- Author
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Müller, Ema and Rožman, Primož
- Subjects
genomska DNA ,presaditev krvotvornih matičnih celic ,genomic DNA ,chimerism ,PCR v realnem času ,bialelni polimorfizmi ,haematopoietic stem cell transplantation ,quantitative PCR ,biallelic polymorphisms ,himerizem - Abstract
Presaditev alogenskih krvotvornih matičnih celic je način zdravljenja določenih malignih in nemalignih bolezni. Stanje po alogenski presaditvi, pri katerem so v prejemnikovem telesu sočasno prisotne celice prejemnika in darovalca krvotvornih matičnih celic, imenujemo himerizem. Z določitvijo himerizma lahko zgodaj zaznamo zaplete kot so ponovitev bolezni, bolezen presadka proti gostitelju in zavrnitev presadka. Sledenje himerizma je zato pomembno za oceno in napoved uspešnosti presaditve krvotvornih matičnih celic in omogoča hitrejše ukrepanje ter poveča možnost ozdravitve bolnika. V nalogi smo za sledenje himerizma po presaditvi krvotvornih matičnih celic uporabili metodo PCR v realnem času in ocenili primernost kompleta setov AlleleSEQR (Celera, ZDA) ter programske opreme AlleleSEQR Suite v1.1 Chimerism Analysis Software (Celera, ZDA) in KMRengine Chimerism Analysis Software (GenDx, Nizozemska). Za testiranje smo uporabili vzorce genomske DNA, izolirane iz periferne krvi 23 bolnikov in njihovih 23 darovalcev. Pri vseh parih smo med 34 bialelnimi polimorfizmi insercij/delecij določili informativne označevalce, ki omogočajo razlikovanje med prejemnikovo in darovalčevo genomsko DNA. Nato smo s testom za kvantitativno določanje himerizma v več zaporednih vzorcih prejemnika, odvzetih v različnih časovnih intervalih po presaditvi krvotvornih matičnih celic, določili delež prejemnikove genomske DNA. Rezultate določitve himerizma smo primerjali s klinično sliko bolnika. Informativnost nabora označevalcev je bila 100 % za vse pare prejemnikov in darovalcev ter je bila po pričakovanju za nesorodne pare večja kot za sorodne. Pri 19 od 23 bolnikov se je klinična slika popolnoma ujemala z rezultati določitve himerizma. Pri štirih bolnikih se klinična slika ni vedno ujemala z rezultatom določitve himerizma. Pri petih bolnikih bi bilo za popolno interpretacijo rezultatov določitve himerizma potrebnih več zaporednih vzorcev. Bolezen presadka proti gostitelju je bila prisotna pri večjem deležu bolnikov s popolnim himerizmom kot pri bolnikih z mešanim himerizmom. Občutljivost metode je bila visoka, saj smo zaznali že 0,02 % himerizem, kar daje zgodnjo informacijo o dinamiki deleža prejemnikove genomske DNA. S testnim sistemom smo uspešno opravili tudi zunanjo kontrolo kakovosti. Zaključimo lahko, da je testni sistem primeren za sledenje himerizma po presaditvi alogenskih krvotvornih matičnih celic pri slovenski populaciji prejemnikov krvotvornih matičnih celic. Allogeneic hematopoietic stem cell transplantation is used in treating certain malignant and non-malignant diseases. Chimerism after allogeneic haematopoietic stem cell transplantation is a condition, in which recipient and donor cells are present in recipient’s body. Chimerism analysis enables early detection of complications, such as disease relapse, graft-versus-host disease and graft rejection. Chimerism monitoring is therefore important for assessment and prediction of successfulness of hematopoietic stem cell transplantation and enables earlier intervention and thus the possibility of a patient being cured is higher. In our study we determined the usefulness of the AlleleSEQR (Celera, USA) kit and software AlleleSEQR Suite v1.1 Chimerism Analysis Software (Celera, USA) and KMRengine Chimerism Analysis Software (GenDx, Netherlands) for chimerism monitoring after hematopoietic stem cell transplantation with the use of quantitative PCR. Genomic DNA samples isolated from peripheral blood of 23 patients and their 23 donors were used for testing. Among 34 biallelic insertion/deletion polymorphisms informative markers were determined, which enables differentiation between donor and recipient genomic DNA. The proportion of recipient genomic DNA in several successive recipient samples, collected in different time intervals after transplantation, was then determined using the test for quantitative chimerism monitoring. The chimerism results were compared with patient’s clinical picture. The informativity of the assay was 100 % for all included donor/recipient pairs and was higher for unrelated pairs than for related. The results of the determination of proportion of genomic DNA matched with the patient’s clinical picture in 19 patients out of 23. The chimerism results did not always match with the clinical picture in four patients. In five patients we would need more successive samples to completely interpret the chimerism results. A smaller proportion of patients with mixed chimerism had graft-versus-host disease compared to the patients with complete chimerism. The sensitivity of the assay is high, as we detected 0,02 % chimerism, which enables earlier information about the change in proportion of recipient genomic DNA. The external quality control was successfully passed with the tested system. We can conclude that the test system is suitable for chimerism monitoring after allogeneic haematopoietic stem cell transplantation for Slovenian population of haematopoietic stem cell recipients.
- Published
- 2019
87. Characterization of mesenchymal stromal cells, isolated from bone marrow of young and old BALB/c mice
- Author
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Žnidarčič, Alenka and Rožman, Primož
- Subjects
udc:602.9:591.81:576.5(043.2) ,mice ,bone marrow ,mezenhimske stromalne celice ,ageing ,staranje ,miši ,kostni mozeg ,mesenchymal stromal cells - Abstract
Mezenhimske stromalne celice (MSC) so eden glavnih virov za celične terapije in tkivno inženirstvo. Sposobne so samoobnavljanja in diferenciacije, lahko uravnavajo imunski odziv in sodelujejo pri celjenju poškodb. S staranjem se njihove regenerativne sposobnosti zmanjšajo. Pri terapijah z MSC se zato poraja vprašanje, kako starost darovalca in celic vpliva na izid zdravljenja. V magistrskem delu smo skušali ugotoviti, kako starost miši BALB/c vpliva na lastnosti njihovih MSC. S pretočno citometrijo smo spremljali izražanje celičnih označevalcev med gojenjem mladih in starih celic, spremljali smo proliferacijo celic s testom MTT, določali smo sposobnost migracije celic s testom celjenja ran in prisotnost senescentnih celic v kulturi. Ugotovili smo, da se mlade celice hitreje delijo, imajo nižji delež senescentnih celic v kulturi in slabše migracijske sposobnosti v primerjavi s starimi celicami. Med izražanjem celičnih označevalcev med skupinama nismo opazili razlik. Mesenchymal stromal cells are one of the main sources for cell therapy and tissue engineering. They are capable of self-renewal and differentiation. They can regulate a body's immune response and participate in its wound-healing process. Their regenerative abilities reduce as they age. MSC therapies therefore raise a question of how the age of the donor affects the outcome of the treatment. In this master's thesis, we tried to determine how the age of BALB/c mice affects the properties of their MSC. We monitored the expression of cell markers during cell culture with flow cytometry. We monitored cell proliferation rate with the MTT assay and analyzed mouse MSC's migration capacities with wound-healing assay. By measuring the β-galactosidase activity we determined the presence of senescent cells in culture. We discovered that young cells divide more rapidly, have a lower proportion of senescent cells in culture and have lower migration capacity when compared to older cells. The expression of cell markers is the same for both cell groups.
- Published
- 2018
88. Določitev plodovega genotipa krvnoskupinskega sistema RhCE iz periferne krvi nosečnic
- Author
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Mikerevič, Tjaša and Rožman, Primož
- Subjects
udc:618.29-053.31(043.3) ,hemolitična bolezen ploda ,hemolitična bolezen novorojenčka ,genotipizacija ,RhCE ,prenatalna diagnostika ,Ledvice ,zunajcelična plodova DNA - Published
- 2016
89. Primerjava dveh laboratorijskih preiskav za potrditev s heparinom izzvane trombocitopenije
- Author
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Pipuš, Mateja and Rožman, Primož
- Subjects
udc:616-074+616-005.6(043.3) ,funkcijski testi ,encimsko imunski test ,s heparinom izzvana trombocitopenija ,heparin ,laboratorijska diagnostika - Published
- 2015
90. Pomen določitve titra protiteles proti eritrocitom v tranfuzijski medicini
- Author
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Poljanc, Anja and Rožman, Primož
- Subjects
aglutinacija ,titriranje eritrocitnih protiteles ,gelske kartice ,sistem ABO ,udc:612.017(043.2) - Published
- 2015
91. An uncommon treatment of totally extruded and lost talus: a case report
- Author
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Barbara U R Smrke, Zoran Marij Arnež, Dragica Smrke, Primož Rožman, Igor Frangež, Borut Gubina, Smrke, Dragica Maja, Rožman, Primož, Gubina, Borut, Frangež, Igor, Smrke, Barbara Rejec, and Arnez, ZORAN MARIJ
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Arthrodesis ,Medicine (all)Extruded talu ,Case Report ,Ankle Fractures ,Free Tissue Flaps ,Talus ,Fracture Fixation, Internal ,Fractures, Open ,Medicine (all)Extruded talus ,Amputation, Traumatic ,Extruded talu ,medicine ,Humans ,Arthrodesi ,Toe Phalanges ,Metatarsal Bones ,Medicine(all) ,Reimplantation ,business.industry ,Soft tissue ,General Medicine ,Plastic Surgery Procedures ,Functional recovery ,Surgery ,medicine.anatomical_structure ,Amputation ,Replantation ,Microsurgical free flap transfer ,Extruded talus ,Functional status ,Ankle ,Metatarsal bones ,business - Abstract
Introduction: Total extrusion and loss of the talus is a rare injury with a wide choice of appropriate treatment, but rarely resulting in a fully functional recovery. We report on an uncommon case, both for the severity of the injury and for the uncommon treatment due to the patient’s rejection of secondary surgery. Case presentation: We treated a 16-year-old Caucasian man with the most extreme variant of a totally extruded and lost talus, accompanied with complex injury of the soft tissues of the ankle and foot. The treatment included urgent microvascular foot reimplantation, microvascular muscle free flap transfer, and temporary fixation. This kind of injury should typically be treated by tibiocalcaneal arthrodesis. However, this was not performed, as after the successful early stages of the treatment he strongly objected to another surgery due to his fully functional status and the successful therapeutic results of our early treatment. Conclusions: The injury described in this case study would ordinarily be treated by amputation, but due to the well-executed treatment in the early stages after the injury, the outcome was satisfying. Surprisingly and against our expectations, the late results of the treatment were successful even without arthrodesis. He is now 37 years old and has a functional foot 21 years after the injury.
- Published
- 2014
92. Mixed cultures of allogeneic dendritic cells are phenotypically and functionally stable - a potential for primary cell-based "off the shelf" product generation.
- Author
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Švajger U and Rožman PJ
- Abstract
Vaccination against tumors using antigen-pulsed dendritic cell (DC) vaccines has greatly evolved over the last decade, with hundreds of active human clinical trials well on the way. The use of an autologous source for DC-based vaccine therapeutics remains the obvious choice in the majority of clinical studies; however, novel evidence suggests that an allogeneic source of DCs can yield success if administered in the right context. One of the challenges facing successful DC vaccination protocols is the generation of large enough numbers of DCs intended for vaccination and standardization of these procedures. In addition, variations in the quality of DC vaccines due to donor-to-donor variation represent an important therapeutic factor. To this day it has not been shown whether DCs from different donors can readily co-exist within the same co-culture for the extended periods required for vaccine manufacture. We demonstrate that generation of allogeneic DC co-cultures, generated from multiple unrelated donors, allows the preservation of their phenotypical and functional properties in vitro for up to 72 hours. Therefore, in the case of an allogeneic vaccination approach, one could ensure large numbers of DCs generated from a primary cell source intended for multiple vaccinations. By generating large amounts of ex vivo manufactured DCs from multiple donors, this would represent the possibility to ensure sufficient amounts of equipotent "off the shelf" product that could e.g. be used for an entire cohort of patients within a study., Competing Interests: The authors declare no conflict of interests., (Copyright © 2021 Termedia.)
- Published
- 2021
- Full Text
- View/download PDF
93. Heparin-induced thrombocytopenia: ELISA optical density value and 4T score in correlation with panel donor platelets activation in functional flow cytometric assay.
- Author
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Železnik K, Rožman P, Kocjan E, and Maličev E
- Subjects
- Aged, Aged, 80 and over, Anticoagulants immunology, Blood Platelets drug effects, Blood Platelets immunology, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Heparin immunology, Humans, Male, Thrombocytopenia blood, Thrombocytopenia immunology, Anticoagulants adverse effects, Heparin adverse effects, Platelet Activation drug effects, Thrombocytopenia chemically induced
- Abstract
Background: Serological assays for the diagnosis of heparin-induced thrombocytopenia (HIT) detect both platelet-activating and platelet non-activating anti-heparin/platelet factor 4 (PF4) antibodies and have therefore a limited positive predictive value. Functional assays confirm the presence of platelet-activating antibodies but require platelets from healthy donors, whose response to patient serum can differ. Our aim was to investigate the correlation between the level of anti-heparin/PF4 antibodies, 4T score, and the extent of panel donor platelet activation in the functional assay., Materials and Methods: In total, 38 sera from enzyme immunoassays (ELISA) positive patients were tested against panel platelets obtained from 10 healthy, randomly selected donors, using our routine flow cytometry functional test for CD62P expression. Levels of anti-heparin/PF4 antibodies from medical and surgical patients and 4T pretest probability scores (where available) were correlated with the number of activated panel platelets., Results: Sera with low ELISA optical density (OD) values (0.4-1) activated on average 5.6, sera with intermediate ELISA OD values (>1-2.5) activated on average 7.3, and sera with high ELISA OD values (>2.5) activated on average 8.6 out of 10 panel platelets. One serum with low 4T score did not activate donor platelets, 12 sera with intermediate 4T score activated on average 6.3 donors, 8 sera with high 4T score activated on average 8.5 panel platelets., Discussion: Sera with higher ELISA OD values activated platelets from a higher number of platelet donors, independently of patient type (medical or surgical). The average number of activated panel platelets increased with rising 4T score. Results indicate that both donor platelet reactivity and quantity of anti-heparin/PF4 antibodies affect the result of the functional assay, meaning special attention is needed in platelet donor selection when testing sera with low levels of antibodies.
- Published
- 2021
- Full Text
- View/download PDF
94. Synergistic Effects of Interferon-γ and Vitamin D 3 Signaling in Induction of ILT-3 high PDL-1 high Tolerogenic Dendritic Cells.
- Author
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Švajger U and Rožman PJ
- Subjects
- Dendritic Cells immunology, Humans, MAP Kinase Signaling System physiology, Phosphatidylinositol 3-Kinases physiology, Receptors, Calcitriol physiology, Signal Transduction physiology, TOR Serine-Threonine Kinases physiology, B7-H1 Antigen physiology, Cholecalciferol pharmacology, Dendritic Cells drug effects, Immune Tolerance immunology, Interferon-gamma pharmacology, Membrane Glycoproteins physiology, Receptors, Immunologic physiology
- Abstract
In the past, interferon (IFN)-γ and vitamin D
3 (vit D3 ) have both been associated with induction of tolerogenic characteristics in human dendritic cells (DCs). Although there are only a few reports on interdependency of their actions, the interplay between IFN-γ and vit D3 has been clearly demonstrated in certain aspects of immune reactivity. Since both agents have been associated with regulation of immune responses, we set out to examine their functional and mechanistic interactions in context of principal regulators of immunity, the DCs. Combined treatment with vit D3 and IFN-γ caused an extensive expression of immunoglobulin-like transcript (ILT)-3 and programmed death ligand (PDL)-1 on γ/D3 DCs, significantly greater than that caused by vit D3 alone. Such γ/D3 DCs retained all general DC characteristics. After CD40 ligand-induced activation, they produced increased amounts of IL-10 with almost absent production of IL-12p70. On the other hand, the co-stimulatory potential of γ/D3 DCs was weak, with cells possessing the capacity to inhibit CD4+ T cell, CD8+ T cell, as well as memory T cell responses. Naive CD4+ T cells stimulated with γ/D3 DCs produced increased amounts of IL-10 with concomitantly low IFN-γ production, upon T cell receptor activation. Additionally, γ/D3 DCs completely inhibited granzyme B expression by CD8+ T cells. The percentage of FoxP3-positive cells in co-cultures with naive CD4+ T cells was significantly higher where γ/D3 DCs were used as stimulators compared to DCs treated with vit D3 alone and it could be partially reversed by PDL-1 blockade. Interestingly, γ/D3 DCs were inefficient at suppressing mDC-induced CD4+ T cell proliferation, but were twice as effective as D3 DCs at suppressing mDC-induced CD8+ T cell proliferation. Blockade of indoleamine-2,3-dioxygenase did not reduce the tolerogenic phenotype induced by IFN-γ and vit D3 treatment. Examination of signaling pathways activation revealed a tendency toward increased ERK and Akt phosphorylation in γ/D3 DCs. Inhibition of MEK/ERK and PI3K/mTOR pathways significantly reduced the expression of ILT-3 and PDL-1 on γ/D3 DCs. In summary, we present the first evidence for existing synergy between IFN-γ and vit D3 in shaping a unique tolerogenic DC activation state., (Copyright © 2019 Švajger and Rožman.)- Published
- 2019
- Full Text
- View/download PDF
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