Jadwiga Drukarczyk

We analyzed for association between the Family with sequence similarity 46, member A (FAM46A) gene (located on chromosome 6q14.1), BCL2-Associated Athanogene 6 (BAG6) gene (located on chromosome 6p21.3) and tuberculosis in Croatian Caucasian. We genotyped the FAM46A rs11040 SNP, FAM46A VNTR and BAG6 rs3117582 polymorphisms in a case-control study with 257 tuberculosis patients and 493 healthy individuals in a Croatian Caucasian population. We found that genotype FAM46A 3/3 (three VNTR repeats homozygote) was associated with susceptibility to tuberculosis (p<0.0015, Pcorr.<0.029, Odds ratio = 2.42, 95% Confidence Interval = 1.34–4.3). This association suggests that the protein domain encoded by the VNTR might be important for the function of the FAM46A protein, which, in turn, could be relevant in developing tuberculosis. In addition, we found that FAM46A rs11040 SNP:FAM46A VNTR:BAG6 haplotype 132 (G-3-C) is associated with susceptibility to tuberculosis (p<0.012, pcorr.<0.024, Odds ratio 3.45, 95% Confidence Interval = 1.26–9.74). This may suggests that the interaction between the FAM46A and BAG6 proteins may be involved in tuberculosis etiology. We found also that infection of human macrophages with heat-killed M. tuberculosis (H37Rv) led to over-expression of FAM46A (VNTR 3/4) transcript. This is the first study to show associations between the FAM46A gene VNTR polymorphisms, FAM46A rs11040 SNP:FAM46A VNTR:BAG6 haplotypes and any disease

Long QT syndrome — a cause of sudden death.

Sindrom dugog QT intervala (LQTS) je primarni aritmijski poremećaj koji može dovesti do pojave malignih ventrikularnih aritmija tipa torsades de pointe (TdP) i iznenadne srčane smrti. Obilježja u elektrokardiogramu (EKG) uključuju produljenje korigiranog QT intervala i abnormalnosti T-vala. Do danas identificirana genetska osnova za LQTS uključuje trinaest podložnih gena za LQTS: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, i KCNJ5. Najčešći genotip su mutacije KCNQ1 te gotovo polovica pacijenata ima tu vrstu mutacije. Navedeni geni kodiraju ionske kanale i regulatorne proteine koji su uključeni u modulaciju struja srčanog akcijskog potencijala. Stečeni oblici LQTS-a mogu također biti uzrokovani genetskim mutacijama, u tim slučajevima nositelji mutacija razvijaju aritmije isključivo u određenim uvjetima (npr. uporaba određenih lijekova). Trenutna terapija uključuje primjenu beta-blokatora, ugradnju implantabilnog kardioverter defibrilatora (ICD) te simpatičku denervaciju srca. LQTS mutacije povezane su s iznenadnom srčanom smrti kod mladih i veoma mladih; a post-mortem genetska testiranja LQTS gena mogu biti korisna kod procjene uzroka iznenadne neobjašnjive smrti (sudden unexplained death). Kaskadni probir koristan je za identificiranje asimptomatskih članova obitelji koji mogu biti pod povećanim rizikom od iznenadne smrti. U ovom preglednom članku prikazali smo gene povezane s LQTS-om zajedno s opisom povezanih patofizioloških mehanizama.Long QT syndrome (LQTS) is a primary arrhythmic disorder that may lead to the precipitation of torsades de pointe (TdP) and sudden death. Electrocardiogram (ECG) features include prolongation of the corrected QT interval and T-wave abnormalities. The genetic basis of LQTS identified to date includes thirteen susceptibility genes for LQTS: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, and KCNJ5. Mutations in KCNQ1 are by far the most frequent genotype with nearly half of the patients carrying KCNQ1 mutations. These genes code for ion channels and regulatory proteins that are involved in the modulation of the currents of the cardiac action potential (AP). Acquired forms of LQTS may also have underlying genetic mutations, in these cases mutation carriers develop arrhythmias only under certain conditions (e.g. use of certain medications). Current therapies include use of beta-blockers, implantable cardioverter defibrillators (ICD) and left cardiac sympathetic denervation. LQTS mutations have been associated with sudden death in the young and very young; and postmortem genetic testing in LQTS genes can be useful when assessing the cause of a sudden unexplained death. Cascade screening is also useful to identify asymptomatic family members that may be at risk of sudden death. Here we have reviewed the genes associated with LQTS along with the description of the related pathophysiological mechanisms

Long QT syndrome — a cause of sudden death.

Sindrom dugog QT intervala (LQTS) je primarni aritmijski poremećaj koji može dovesti do pojave malignih ventrikularnih aritmija tipa torsades de pointe (TdP) i iznenadne srčane smrti. Obilježja u elektrokardiogramu (EKG) uključuju produljenje korigiranog QT intervala i abnormalnosti T-vala. Do danas identificirana genetska osnova za LQTS uključuje trinaest podložnih gena za LQTS: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, i KCNJ5. Najčešći genotip su mutacije KCNQ1 te gotovo polovica pacijenata ima tu vrstu mutacije. Navedeni geni kodiraju ionske kanale i regulatorne proteine koji su uključeni u modulaciju struja srčanog akcijskog potencijala. Stečeni oblici LQTS-a mogu također biti uzrokovani genetskim mutacijama, u tim slučajevima nositelji mutacija razvijaju aritmije isključivo u određenim uvjetima (npr. uporaba određenih lijekova). Trenutna terapija uključuje primjenu beta-blokatora, ugradnju implantabilnog kardioverter defibrilatora (ICD) te simpatičku denervaciju srca. LQTS mutacije povezane su s iznenadnom srčanom smrti kod mladih i veoma mladih; a post-mortem genetska testiranja LQTS gena mogu biti korisna kod procjene uzroka iznenadne neobjašnjive smrti (sudden unexplained death). Kaskadni probir koristan je za identificiranje asimptomatskih članova obitelji koji mogu biti pod povećanim rizikom od iznenadne smrti. U ovom preglednom članku prikazali smo gene povezane s LQTS-om zajedno s opisom povezanih patofizioloških mehanizama.Long QT syndrome (LQTS) is a primary arrhythmic disorder that may lead to the precipitation of torsades de pointe (TdP) and sudden death. Electrocardiogram (ECG) features include prolongation of the corrected QT interval and T-wave abnormalities. The genetic basis of LQTS identified to date includes thirteen susceptibility genes for LQTS: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, and KCNJ5. Mutations in KCNQ1 are by far the most frequent genotype with nearly half of the patients carrying KCNQ1 mutations. These genes code for ion channels and regulatory proteins that are involved in the modulation of the currents of the cardiac action potential (AP). Acquired forms of LQTS may also have underlying genetic mutations, in these cases mutation carriers develop arrhythmias only under certain conditions (e.g. use of certain medications). Current therapies include use of beta-blockers, implantable cardioverter defibrillators (ICD) and left cardiac sympathetic denervation. LQTS mutations have been associated with sudden death in the young and very young; and postmortem genetic testing in LQTS genes can be useful when assessing the cause of a sudden unexplained death. Cascade screening is also useful to identify asymptomatic family members that may be at risk of sudden death. Here we have reviewed the genes associated with LQTS along with the description of the related pathophysiological mechanisms

Hip osteoarthritis susceptibility is associated with IL1B −511(G>A) and IL1 RN (VNTR) genotypic polymorphisms in Croatian caucasian population

Among the predisposing factors to osteoarthritis (OA), a frequent destructive joint disease, is the complex genetic heritage including the interleukin‐1 family members like the IL1β (IL1B) and the IL1 receptor antagonist (IL1RN) genes. The aim of this study was to investigate allelic and genotypic frequencies of the IL1B gene single nucleotide polymorphism (SNP) at −511(G>A) and the variable number tandem repeat (VNTR) in the IL1RN gene in a Croatian Caucasian population of hip OA (HOA) cases and healthy controls. A total of 259 HOA patients with total hip replacement (THR) and 518 healthy blood donors as controls were genotyped for IL1B gene SNP −511(G>A) and the VNTR in the IL1RN gene associated with HOA. The genotype G/A (1/2) at IL1B was significantly associated with the protection of the HOA (p A) and IL1RN (VNTR) were found associated with the HOA. The haplotype 1–2 at these loci had only a trend to susceptibility (p = 0.065). Haplotype 1–3 had a significant male bias in diseased. Furthermore, genotype comprising 2–1/2–2 haplotypes was found significantly associated with predisposition to HOA (p = 0.027, OR = 2.23, 95% CI = 1.03–4.88), whereas genotype 1–1/2–2 with protection to disease (p = 0.028, OR = 0.65, 95% CI = 0.43–0.97). Our findings suggest that HOA in Croatian population might have a different genetic risk regarding the IL1 locus than has been reported for other Caucasian populations previously

Domain-swapped T cell receptors improve the safety of TCR gene therapy

T cells engineered to express a tumor-specific αβ T cell receptor (TCR) mediate anti-tumor immunity. However, mispairing of the therapeutic αβ chains with endogenous αβ chains reduces therapeutic TCR surface expression and generates self-reactive TCRs. We report a general strategy to prevent TCR mispairing: swapping constant domains between the α and β chains of a therapeutic TCR. When paired, domain-swapped (ds)TCRs assemble with CD3, express on the cell surface, and mediate antigen-specific T cell responses. By contrast, dsTCR chains mispaired with endogenous chains cannot properly assemble with CD3 or signal, preventing autoimmunity. We validate this approach in cell-based assays and in a mouse model of TCR gene transfer-induced graft-versus-host disease. We also validate a related approach whereby replacement of αβ TCR domains with corresponding γδ TCR domains yields a functional TCR that does not mispair. This work enables the design of safer TCR gene therapies for cancer immunotherapy

ZADOVOLJSTVO KORISNIKA KAO ČINITELJ UNAPRIJEĐENJA USLUGE STP BRIONI D. D. PULA

Uvođenjem marketinških aktivnosti u određivanju ponude usluge stanice za tehniĉki pregled dovodi do sve veće konkurentnosti i boljeg poslovanja samog poduzeća na tržištu što pridonosi većim prihodima i sve većim zadovoljstvom korisnika usluga. Rezultat konstantnog praćenja te ispitivanja ponašanja korisnika i trţišta odraz je profitabilnog poslovanja. Usluga je neopipljive prirode i ne moţe se posjedovati u obliku aktivnosti ili niza aktivnosti pa je potrebno puno istraţivanja, vještina, znanja i sposobnosti da bi se prenijela korisniku. Kroz organizaciju, planiranje i krajnju kontrolu da li sustav kao takav funkcionira i uvid u njegovu kvalitetnost i uĉinkovitost postiţe se sve veća razina kvalitete usluge. Sve se to na kraju svodi na zadovoljstvo korisnika koji će se uvijek vratiti te donijeti profit, pozitivan glas i nove korisnike. Poduzeće na taj naĉin stvara sliku kao respektabilnog konkurenta stalnim unaprjeđenjem tehnologije, organizacije rada te podizanjem razine kvalitete usluge. Posebna se pozornost mora posvetiti sigurnosti i udobnosti putnika i to pripremom sredstava za rad redovitim odrţavanjem i redovitim pregledima istih. Jedna od bitnijih stavki sigurnosti putnika i sudionika u prometu je sustav tehniĉkih pregleda. Obavljanjem tehniĉkih pregleda prijevoznih sredstava vrši se provođenje zakona i pravilnika. Istima se određuju propisani uvjeti kojima moraju udovoljavati vozila koja sudjeluju u cestovnom prometu

ZADOVOLJSTVO KORISNIKA KAO ČINITELJ UNAPRIJEĐENJA USLUGE STP BRIONI D. D. PULA

Uvođenjem marketinških aktivnosti u određivanju ponude usluge stanice za tehniĉki pregled dovodi do sve veće konkurentnosti i boljeg poslovanja samog poduzeća na tržištu što pridonosi većim prihodima i sve većim zadovoljstvom korisnika usluga. Rezultat konstantnog praćenja te ispitivanja ponašanja korisnika i trţišta odraz je profitabilnog poslovanja. Usluga je neopipljive prirode i ne moţe se posjedovati u obliku aktivnosti ili niza aktivnosti pa je potrebno puno istraţivanja, vještina, znanja i sposobnosti da bi se prenijela korisniku. Kroz organizaciju, planiranje i krajnju kontrolu da li sustav kao takav funkcionira i uvid u njegovu kvalitetnost i uĉinkovitost postiţe se sve veća razina kvalitete usluge. Sve se to na kraju svodi na zadovoljstvo korisnika koji će se uvijek vratiti te donijeti profit, pozitivan glas i nove korisnike. Poduzeće na taj naĉin stvara sliku kao respektabilnog konkurenta stalnim unaprjeđenjem tehnologije, organizacije rada te podizanjem razine kvalitete usluge. Posebna se pozornost mora posvetiti sigurnosti i udobnosti putnika i to pripremom sredstava za rad redovitim odrţavanjem i redovitim pregledima istih. Jedna od bitnijih stavki sigurnosti putnika i sudionika u prometu je sustav tehniĉkih pregleda. Obavljanjem tehniĉkih pregleda prijevoznih sredstava vrši se provođenje zakona i pravilnika. Istima se određuju propisani uvjeti kojima moraju udovoljavati vozila koja sudjeluju u cestovnom prometu

Struktura i funkcija gena receptora limfocita T za antigen i MHC : doktorska disertacija

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