25 research outputs found
Immunoglobulin heavy chain gene rearrangements in patients with Gaucher disease
Uvod: Nekoliko studija u literaturi navode dokaze o poveÄanoj incidenci hematoloÅ”kih komplikacija u bolesnika sa GoÅ”eovom boleÅ”Äu, ukljuÄujuÄi monoklonsku i poliklonsku gamapatiju i hematoloÅ”ke malignitete, a posebno multipli mijelom. Metode: OdreÄivana je serumska koncentracija imunoglobulina kao i rearanžman gena za teÅ”ki lanac imunoglobulina - IGH, PCR analizom. Klonalni PCR produkti su direktno sekvencirani i analizirani koristeÄi adekvatne alate i baze podataka. Monoklonski proteini seruma su detektovani i identifikovani metodom elektroforeze. Rezultati: MeÄu 27 bolesnika, klonalni IGH rearanžman je otkriven kod osmoro, od kojih je petoro imalo i monot klonski protein u serumu. Hipergamaglobulinemija je otkrivena u 9/27 bolesnika. Podaci o praÄenju za 17 bolesnika su pokazali da je klonalni rearanžman ostao isti u Äetiri bolesnika, dok je u jednog bolesnika iÅ”Äezao tokom perioda praÄenja. Preostalih 12/17 bolesnika nisu imali klonalni IGH rearanžman niti su ga stekli nakon perioda praÄenja. ZakljuÄak: Iako klonska ekspanzija može da nastane relativno rano u toku GoÅ”eove bolesti, barem sudeÄi prema rearanžmanu IGH gena, detektovani klonovi mogu biti tranzitorni. Pažljivo kliniÄko praÄenje ovih bolesnika je obavezno, ukljuÄujuÄi i nadzor nad limfoidnim neoplazmama, posebno multiplim mijelomom.Background: Several studies support the evidence of increased incidence of hematological complications in Gaucher disease including monoclonal and polyclonal gammopathies and blood malignancies, especially multiple myeloma. Methods: Serum concentrations of immunoglobulins and PCR analysis of the IGH gene rearrangements were performed. The clonal PCR products were directly sequenced and analyzed with the appropriate database and tools. Serum monoclonal proteins were detected and identified by electrophoresis. Results: Among 27 Gaucher patients, clonal IGH rearrangement was discovered in eight, with 5/8 having also serum monoclonal protein. Elevated immunoglobulins were detected in 9/27 patients. Follow-up data for 17 patients showed that the clonal rearrangement remained the same in four of them, however, in one patient it disappeared after the follow-up period. The remaining 12/17 patients were without previous IGH clonal rearrangement and remained so after the follow-up. Conclusions: Although clonal expansion may occur relatively early in the disease course, at least judging by the IGH gene rearrangements in Gaucher patients, the detected clones may be transient. A careful clinical follow-up in these patients is mandatory, including monitoring for lymphoid neoplasms, especially multiple myeloma
The importance of genomic profiling for differential diagnosis of pediatric lung disease patients with suspected ciliopathies
Uvod/Cilj Izmenjena funkcija aksonemalne strukture dovodi do ciliopatija (motornih i senzornih), koje su do sada povezane sa brojnim pedijatrijskim poremeÄajima, ukljuÄujuÄi i respiratorne. Primarna cilijarna diskinezija (PCD) najÄeÅ”Äa je ciliopatija, koja nastaje kao posledica poremeÄaja u motornim cilijama. Promenjena struktura i/ ili funkcija motornih cilija dovodi do neonatalnog respiratornog distresa, hroniÄnog vlažnog kaÅ”lja, simptoma nazalne sekrecije, bronhoektazija, hroniÄne upale sinusa i uha, a 50% bolesnika ima i situs inversus. Ovi simptomi su priliÄno uobiÄajeni kod male dece i u drugim stanjima; stoga je uspostavljanje precizne dijagnoze otežano. Cilj ovog istraživanja je ukazivanje na znaÄaj genomskog profilisanja bolesnika i dizajniranje strategije za genetiÄku analizu podataka kod bolesnika suspektnih na ciliopatije sa kliniÄkom slikom sliÄnom drugim bolestima pluÄa. Metode Sproveli smo bioinformatiÄku analizu podataka dobijenih metodom sekvenciranja nove generacije 21 bolesnika sa potvrÄenom ili suspektnom dijagnozom PCD-a. Analizirano je 93 gena: 29 PCD gena, 45 gena asociranih sa pojedinaÄnim simptomima pluÄnih bolesti i 19 gena asociranih sa senzornim ciliopatijama. Rezultati Dizajnirani algoritam za genetiÄku analizu NAM je omoguÄio da potvrdimo kliniÄku i uspostavimo genetiÄku dijagnozu kod 17/21 (80,95%) bolesnika, meÄu kojima je 11/21 (52,38%) PCD bolesnika. Kod 3/21 (14,28%) bolesnika detektovane su monoalelske varijante u PCD genima, kod 6/21 (28,57%) bolesnika detektovane su varijante u genima relevantnim za druga pluÄna oboljenja, dok je kod 1/21 (4,76%) bolesnika genetiÄka osnovna bolesti ostala nerazjaÅ”njena. ZakljuÄak Dizajniranje strategije za lakÅ”e i brže uspostavljanje konaÄne dijagnoze ciliopatija je obavezno i ukljuÄuje i kliniÄku i genetiÄku potvrdu bolesti.Introduction/Objective Dysfunction of the axonemal structure leads to ciliopathies. Sensory and mo-tile ciliopathies have been associated with numerous pediatric diseases, including respiratory diseases. Primary ciliary dyskinesia (PCD) is ciliopathy linked to the dysfunction of motile cilia. Motile ciliary dys-function in childhood leads to chronic rhinosinusitis, persistent cough, neonatal respiratory distress, bronchiectasis, and situs inversus (SI) have 50% of patients. These symptoms are common among pediatric lung diseases, which additionally makes it difficult to establish the accurate diagnosis. The aim of the study was to point out the significance of genomic profiling for patients with suspected ciliopathies and to design a strategy for genomic analysis relevant for differential diagnosis of lung disease patients with suspected ciliopathies. Methods We conducted a bioinformatic analysis of data generated by New Generation Sequencing (NGS) approach of 21 patients with final or suspected diagnosis of PCD. It was analyzed 93 genes: 29 PCD genes, 45 genes related to individual symptoms of lung diseases, and 19 genes related to sensory ciliopathies. Results the algorithm we have designed, enabled us to establish the clinical and genetic diagnosis for 17/21 (80.95%) patients, among which 11/21 (52.38%) were PCD patients. In 3/21 (14.28%) patients we detected monoallelic variants in PCD disease-causing genes. In 6/21 (28.57%) patients, variants in genes for other pulmonary diseases were detected, and for one patient, genetic background of disease remained unclear. Conclusion an improved strategy for easier and faster establishment of final diagnosis of ciliopathies is mandatory and includes both, clinical and genetic confirmation of disease
Supplementary data for article: MarkoviÄ, V.; Markovic, S.; Janicijevic, A.; RodiÄ, M.; Leovac, V. M.; TodoroviÄ, N.; TrifunoviÄ, S. S.; JoksoviÄ, M. D. Mechanistic Investigation and DFT Calculation of the New Reaction between S-Methylisothiosemicarbazide and Methyl Acetoacetate. Structural Chemistry 2013, 24 (6), 2127ā2136. https://doi.org/10.1007/s11224-013-0223-3
Supplementary material for: [https://doi.org/10.1007/s11224-013-0223-3]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1455
Supplementary material for the article: MiloÅ”ev, M. Z.; JakovljeviÄ, K.; JoksoviÄ, M. D.; StanojkoviÄ, T.; MatiÄ, I. Z.; PeroviÄ, M.; TeÅ”iÄ, V.; Kanazir, S.; MladenoviÄ, M.; RodiÄ, M. V.; et al. Mannich Bases of 1,2,4-Triazole3-Thione Containing Adamantane Moiety: Synthesis, Preliminary Anticancer Evaluation, and Molecular Modeling Studies. Chemical Biology and Drug Design 2017, 89 (6), 943ā952. https://doi.org/10.1111/cbdd.12920
Supporting Information: [https://doi.org/10.1111/cbdd.12920]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2482]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3221
Supplementary material for the article: MiloÅ”ev, M. Z.; JakovljeviÄ, K.; JoksoviÄ, M. D.; StanojkoviÄ, T.; MatiÄ, I. Z.; PeroviÄ, M.; TeÅ”iÄ, V.; Kanazir, S.; MladenoviÄ, M.; RodiÄ, M. V.; et al. Mannich Bases of 1,2,4-Triazole3-Thione Containing Adamantane Moiety: Synthesis, Preliminary Anticancer Evaluation, and Molecular Modeling Studies. Chemical Biology and Drug Design 2017, 89 (6), 943ā952. https://doi.org/10.1111/cbdd.12920
Supporting Information: [https://doi.org/10.1111/cbdd.12920]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2482]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3221
Efekti selenita na metabolizam glutationa kod gljive Phycomyces blakesleeanus
Elementarni selen je najmanje biotoksiÄan oblik selena u prirodi, dok selen-oksianjoni mogu biti toksiÄni zbog znaÄajne pokretljivosti i rastvorljivosti u vodi. MikrobioloÅ”ka redukcija selena +4 (selenit) u elementarni selen je stoga od presudnog znaÄaja za smanjenje bioraspoloživosti ovog elementa.1 Visoka reaktivnost selen-oksianjona sa tiolnim grupama, kao i formiranje kiseoniÄnih radikala u reakciji sa glutationom implicira da oksidativni stres doprinosi toksiÄnosti selena.2 Tokom bioloÅ”ke redukcije selenita se proizvodi velika koliÄina peroksida Äime se indukuje ekspresija gena koji kodiraju enzime antioksidativnog metabolizma, Å”to ukljuÄuje i enzime metabolizma glutationa.1 Micelijum gljive Phycomyces blakesleeanus star 24 sata je tretiran 10 mM rastvorom selenita. Uzorci su nakon odreÄenih vremenskih intervala (1, 5, 10, 30, 60 minuta, 24 i 96 sati) ispirani i homogenizovani, nakon Äega je meren sadržaj glutationa i specifiÄna aktivnost enzima: peroksidaza (POD), katalaza (CAT), superoksid dismutaza (SOD), glutation peroksidaze (GPx), glutation-S-transferaze (GST) i glutation reduktaze (GR). Nakon dodavanja selenita utvrÄen je pad koliÄine ukupnog glutationa u micelijumu. Aktivnost POD i SOD je rasla do 60 minuta, nakon Äega je opadala. Aktivnost CAT opadala je odmah po dodatku selenita. Najizraženija je bila promena aktivnosti GPx gde je zabeležen znaÄajan porast, dok su promene aktivnosti GST i GR bile manje izražen
PRODUCTION AND CHARACTERISATION OF SELENIUM NANOPARTICLES BY MYCELIUM OF FUNGUS PHYCOMYCES BLAKESLEEANUS
In this study, mycelium of fungus Phycomyces blakesleeanus was exposed to soluble toxic form of selenium, selenite (Se+4), to examine its ability to reduce it to nanoparticles. Red coloration appeared after only a few hours of incubation with 10 mM Se+4 indicating formation of selenium nanoparticles (SeNPs). SEM-EDS confirmed pure selenium NPs with an average diameter of 57 nm, which indicates to potentially very good medical, optical and photoelectric characteristics. Raman spectroscopy showed several structural forms of SeNPs formed in the extracellular space with a monoclinic Se8 chain as the most represented, and the other observed forms were trigonal Se polymer chain, Se8 ring and Se6 chain structures
Activities of antioxidant enzymes in mycelium of fungus Phycomyces blakesleeanus
Phycomyces blakesleeanus is a strict aerobic filamentous fungus often used as a model system in studies of physiology, genetics, environmental sensing, and metabolism. As all other aerobic organisms, this fungus faces the toxic effects of oxygen-reactive species, but data about its antioxidative defense systems are scarce. The aim of this research was to examine the activities of three antioxidant enzymes during different phases of growth. The fungus was grown in two ways, in Petri dishes, and on a shaker in Erlenmeyer flasks. The activities of superoxide dismutase
(SOD) and peroxidase (POD) were determined spectrophotometrically, while the activity of catalase (CAT) was determined polarographically with a Clark-type oxygen electrode. The highest activities of SOD were noticed in mycelia grown in Erlenmeyer flasks in the stationary phase of growth. In mycelia grown in Petri dishes, the highest activities of POD (0,014U/mg protein) and CAT (20,63 U/mg protein) were noticed in the early exponential phase. The activities of these two enzymes decreased with mycelial growth. In mycelia grown in Erlenmeyer flasks, POD and CAT
showed similar behavior, but differences in activities between exponential and stationary phases were smaller and the highest activities were noticed in the mid-exponential to stationary phase of growth (0,011U/mg protein for POD and 17,21U/mg protein for CAT). High activities of these two enzymes indicated increased production of H2O2 and pointed out the importance of this phase for mycelia grown in this way
Efekti vanadata na aktivnost antioksidativnih enzima tokom razviÄa gljive Phycomyces blakesleeanus
Vanadijum je prelazni metal, koji se može naÄi u brojnim oksidacionim stanjima, pri Äemu su najznaÄajnija +4 (vanadil) i +5 (vanadat). S obzirom da gljive apsorbuju vanadijum, one predstavljaju glavni put njegovog ulaska u ekosistem.1 Vanadat je izuÄavan kao potencijalni antidijabetski i antikancerogeni agens, ali zbog svoje komplikovane hemije se ne koristi u terapijama. Mnogi efekti vanadijuma na Äeliju nisu poznati, a meÄu njima je i efekat na sisteme antioksidativne zaÅ”tite.2 U ovom istraživanju je ispitivana aktivnost superoksid dismutaza (SOD), peroksidaza (Prx) i katalaza (CAT) tokom razliÄitih faza razvoja gljive Phycomyces blakesleeanus, a kao odgovor na tretman micelijuma vanadatom. Efekat je praÄen kod gljiva starosti 20 h, 36 h i 56 h, koje su izlagane 10 mM vanadatu tokom 1 h, 3 h ili 5 h. U eksponencijalnoj fazi razvoja (20 h) zabeležen je porast aktivnosti Prx i to 45Ā±7% nakon 1 h, odnosno 19Ā±7% nakon 5 h tretmana. Na prelasku iz eksponencijalne u stacionarnu fazu razvoja (36 h) 10 mM vanadat nije doveo do promene aktivnosti Prx u tretiranim uzorcima, dok je u stacionarnoj fazi razvoja (56 h) ponovo zabeležen porast aktivnosti Prx i to 22Ā±4% nakon 1 h, odnosno 31Ā±19% nakon 3 h tretmana. Porast aktivnosti SOD je zabeležen samo u stacionarnoj fazi razvoja, nakon 1 h tretmana i iznosi 26Ā±2%. Nije uoÄena jasna promena aktivnosti CAT tretiranih u odnosu na kontrolne uzork
Supplementary data for article: FilipoviÄ, N. R.; BjelogrliÄ, S. K.; MarinkoviÄ, A.; VerbiÄ, T.; CvijetiÄ, I.; Sencanski, M.; RodiÄ, M.; VujÄiÄ, M.; SladiÄ, D.; Strikovic, Z.; et al. Zn(II) Complex with 2-Quinolinecarboxaldehyde Selenosemicarbazone: Synthesis, Structure, Interaction Studies with DNA/HSA, Molecular Docking and Caspase-8 and-9 Independent Apoptose Induction. RSC Advances 2015, 5 (115), 95191ā95211. https://doi.org/10.1039/c5ra19849f
Supplementary material for: [https://doi.org/10.1039/c5ra19849f]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1960