Microchimaerismus mint terhességi örökség = Microchimerism, as an inheritance from pregnancy

Terhesség során, a méhlepényen keresztüli kétirányú sejtforgalom következtében idegen sejtek vagy DNS kerülnek mind az anya, mind a magzat szervezetébe. Ez a jelenség a magzati, illetve anyai microchimaerismus. Ezen sejtek akár évtizedekkel a szülés után is kimutathatók a gazdaszervezetből. Annak ellenére, hogy számos kutatás foglalkozik e jelenséggel, a microchimaerismus egészségben és betegségekben betöltött jelentősége továbbra is csak kevéssé ismert. Cikkünkben áttekintést szeretnénk nyújtani a tudomány jelenlegi állásáról. A microchimaerismus lehetséges szerepét leginkább autoimmun folyamatok patogenezisében, nem autoimmun betegségek és tumorok kialakulásának vagy éppen regressziójának magyarázatában, továbbá a transzplantációs immunológia lehetséges komponenseként vizsgálták. A microchimaerismus jelensége fontos praenatalis noninvazív diagnosztikai lehetőségeket rejthet magában, megszüntetve a jelenleg alkalmazott vizsgálóeljárásokkal együtt járó vetéléskockázatot. A folyamatosan fejlődő sejtidentifikációs és -dúsító eljárásoknak köszönhetően várhatóan egyre több, a szervezetben lezajló folyamatról derül majd ki, hogy a terhességi örökségként az anyai és magzati szervezetbe került microchimaerasejtek és DNS szerepet játszanak bennük. Orv. Hetil., 2010, 49, 2019–2024. | During pregnancy, due to the bidirectional traffic through the placenta, chimera cells or DNA gets into the mother’s and her fetus’ body. This is the phenomenon of fetal and maternal microchimerism. These cells, even decades after the birth, can be detected in the host. Despite the fact that a lot of research-team deals with this phenomenon, the importance of microchimerism in health and diseases remains little known. In this article, we aimed to give an overview of the current state of science about this topic. The possible role of microchimerism studied mostly in the pathogenesis of autoimmune processes, non-autoimmune diseases and tumors, or even in the regression of them; it can be as well as a possible component of transplant immunology. The phenomenon of microchimerism could mean important opportunity in the non-invasive prenatal diagnosis, cutting off the currently associated risk of abortion. Due to the constantly developing cell identification- and enrichment procedures, it is expected to be revealed in more and more processes of the human body, that microchimera cells and DNA, as an inheritance of pregnancy, play a role in them. Orv. Hetil., 2010, 49, 2019–2024

Új generációs szekvenálás és használata az aneuploidiák nem invaziv praenatalis vizsgálatában

The development of the new generation sequencing techniques brought a new era in the field of DNA sequencing, that also revolutionized the prenatal screening for aneuploidy. In order to provide a more complete view, the authors describe some first generation methods as well as the theoretical and technical background of the next generation methods. In the second part of this review, the authors focuse on non-invasive prenatal testing, which is a fetal cell-free DNA based method requiring advanced sequencing procedures. After discussing the theoretical and technical background, the authors review current application and utility of non-invasive prenatal testing. They conclude that non-invasive prenatal testing is the most effective screening test in high risk pregnancies and its efficiency can be justified in studies involving low risk pregnancies as well. Orv. Hetil., 2015, 156(26), 1041-1048

A terhességet megelőzően alkalmazott hosszabb távú orális fogamzásgátlás mint a magzati 21-es triszómia lehetséges kockázatcsökkentő tényezője idős anyai életkorban vállalt terhességben

Abstract: Down syndrome is the most common autosomal chromosomal abnormality. According to the classical interpretation, it is the result of meiotic nondisjunction. Its occurrence is more common in advanced maternal age. Despite intensive research, pathophysiology of this genetic disorder is not fully understood. According to recent studies, a different kind of mechanism may be found in the background of trisomy 21 than was previously considered. Based on the ovarian mosaicism model, the cause of trisomy 21 (or any common trisomy) is a segregation error of a chromosome in premeiotic mitosis. The cell entering meiosis will be an oocyte with preexisting trisomy, where its (so-called ?secondary?) nondisjunction is essential. Maturation of the trisomic oocytes appears to fall behind the disomic oocytes, resulting in their relative accumulation in the ovaries as time progresses. The ratio of trisomic/disomic cells becomes less favorable in maternal maturity. If ovulation is inhibited ? although the number of oocytes will continue to decline due to apoptosis ? it can be assumed that the trisomic/disomic oocyte ratio remains more favorable with the progression of age. In our summary report, presenting and updating our previous data, we would like to propose that ? according to ovarian mosaicism model ? long-term oral contraception in the anamnesis may be beneficial in pregnancies with advanced maternal age. Orv Hetil. 2018; 159(28): 1146?1152

Use of routinely collected amniotic fluid for whole-genome expression analysis of polygenic disorders

BACKGROUND: Neural tube defects related to polygenic disorders are the second most common birth defects in the world, but no molecular biologic tests are available to analyze the genes involved in the pathomechanism of these disorders. We explored the use of routinely collected amniotic fluid to characterize the differential gene expression profiles of polygenic disorders. METHODS: We used oligonucleotide microarrays to analyze amniotic fluid samples obtained from pregnant women carrying fetuses with neural tube defects diagnosed during ultrasound examination. The control samples were obtained from pregnant women who underwent routine genetic amniocentesis because of advanced maternal age (>35 years). We also investigated specific folate-related genes because maternal periconceptional folic acid supplementation has been found to have a protective effect with respect to neural tube defects. RESULTS: Fetal mRNA from amniocytes was successfully isolated, amplified, labeled, and hybridized to whole-genome transcript arrays. We detected differential gene expression profiles between cases and controls. Highlighted genes such as SLA, LST1, and BENE might be important in the development of neural tube defects. None of the specific folate-related genes were in the top 100 associated transcripts. CONCLUSIONS: This pilot study demonstrated that a routinely collected amount of amniotic fluid (as small as 6 mL) can provide sufficient RNA to successfully hybridize to expression arrays. Analysis of the differences in fetal gene expressions might help us decipher the complex genetic background of polygenic disorders

Paroxysmalis nocturnalis haemoglobinuriával szövődött várandósság ritka esete

Paroxysmal nocturnal hemoglobinuria is a rare hematological disease. It is associated with increased maternal and fetal complications to such an extent that pregnancy has been considered relatively contraindicated in woman with paroxysmal nocturnal haemoglobinuria. Recently, eculizumab, a monoclonal antibody, has been shown to decrease complications during pregnancies. The highest risk is thromboembolic complication and, therefore, anticoagulant is a standard therapy during pregnancy. In the presented case, a 29-year-old woman with a 5-year history of paroxysmal nocturnal haemoglobinuria had a pregnancy. It was her first pregnancy and was complicated by a sinus thrombosis at the 11th gestational week. After the introduction of eculizumab treatment, the remaining period of pregnancy and delivery were uncomplicated. There are only a few cases in the literature about pregnancy in woman with paroxysmal nocturnal hemoglobinuria who are treated with eculizumab. This monoclonal antibody seems to be safe and it likely prevents many of the complications otherwise observed. Orv. Hetil., 2016, 157(23), 916-918

Quantitatív fluoreszcens polimeráz láncreakcióval kimutatható magzati chromosoma-rendellenességek

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Effect of the Nature of Donor Atoms on the Thermodynamic, Kinetic and Relaxation Properties of Mn(II) Complexes Formed With Some Trisubstituted 12-Membered Macrocyclic Ligands

During the past few years increasing attention has been devoted to Mn(II) complexes as possible substitutes for Gd(III) complexes as contrast agents in MRI. Equilibrium (log KMnL or pMn value), kinetic parameters (rates and half-lives of dissociation) and relaxivity of the Mn(II) complexes formed with 12-membered macrocyclic ligands were studied. The ligands were selected in a way to gain information on how the ligand rigidity, the nature of the donor atoms in the macrocycle (pyridine N, amine N, and etheric O atom), the nature of the pendant arms (carboxylates, phosphonates, primary, secondary and tertiary amides) affect the physicochemical parameters of the Mn(II) complexes. As expected, decreasing the denticity of DOTA (to afford DO3A) resulted in a drop in the stability and inertness of [Mn(DO3A)]− compared to [Mn(DOTA)]2−. This decrease can be compensated partially by incorporating the fourth nitrogen atom into a pyridine ring (e.g., PCTA) or by replacement with an etheric oxygen atom (ODO3A). Moreover, the substitution of primary amides for acetates resulted in a noticeable drop in the stability constant (PC3AMH), but it increased as the primary amides (PC3AMH) were replaced by secondary (PC3AMGly) or tertiary amide (PC3AMPip) pendants. The inertness of the Mn(II) complexes behaved alike as the rates of acid catalyzed dissociation increased going from DOTA (k1 = 0.040 M−1s−1) to DO3A (k1 = 0.45 M−1s−1). However, the rates of acid catalyzed dissociation decreased from 0.112 M−1s−1 observed for the anionic Mn(II) complex of PCTA to 0.0107 M−1s−1 and 0.00458 M−1s−1 for the cationic Mn(II) complexes of PC3AMH and PC3AMPip ligands, respectively. In spite of its lower denticity (as compared to DOTA) the sterically more hindered amide complex ([Mn(PC3AMPip)]2+) displays surprisingly high conditional stability (pMn = 8.86 vs. pMn = 9.74 for [Mn(PCTA)]−) and excellent kinetic inertness. The substitution of phosphonates for the acetate pendant arms (DOTP and DO3P), however, resulted in a noticeable drop in the conditional stability as well as dissociation kinetic parameters of the corresponding Mn(II) complexes ([Mn(DOTP)]6− and [Mn(DO3P)]4−) underlining that the phosphonate pedant should not be considered as a suitable building block for further ligand design while the tertiary amide moiety will likely have some implications in this respect in the future

Effect of the Nature of Donor Atoms on the Thermodynamic, Kinetic and Relaxation Properties of Mn(II) Complexes Formed With Some Trisubstituted 12-Membered Macrocyclic Ligands

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Praenatalis genetikai diagnosztika az anyai vérkeringésbe kerülő magzati sejtekből- helyzetkép az eddigi eredményekről

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A szülészeti ellátás mennyiségi és minőségi mutatói a Baross utcai Női Klinikán 1990 és 2006 között = Quality and quantity of obstetrical care in Baross Street Department of Obstetrics and Gynecology between 1990 and 2006

Célkitűzés és módszer: A szerzők a Semmelweis Egyetem I. Szülészeti és Nőgyógyászati Klinikáján 1990. január 1. és 2006. december 31. között a terhesség 24. és 42. hete között befejeződött 48 794 terhesség adatait elemezték olyan számítógépes nyilvántartási rendszerük adataira támaszkodva, mely a szülészeti, genetikai és neonatológiai ellátás komplexitását tükrözi. Eredmények: A szülésszám az adott 17 évben folyamatosan emelkedett, 1990-ben 2299, míg 2006-ban 3861 szülést regisztráltak. A korai neonatalis mortalitás fokozatosan csökkent (1990-ben 22/1000 élveszületés, 2006-ban 6/1000 élveszületés). Ha nem vesszük figyelembe az 1000 g súly alatt meghalt, az intézeten kívül intrauterin elhalt és a malformatio miatti szülésindukciók következtében születetteket, a perinatalis mortalitás igen alacsony, az utóbbi 7 évben 6/1000 szülés alatti, 2004-ben 2,8/1000 szülés, 2005-ben és 2006-ban pedig 1,8–1,9/1000 szülés! A neonatalis és csecsemőkori mortalitás adataiban is jelentős csökkenés tapasztalható. A császármetszések száma a vizsgált időszakban fokozatosan emelkedett; gyakoriságuk 1990–1991-ben 15–20%, az utóbbi években pedig 35% körül mozog. A főbb javallatok között szerepel az előzetes császármetszés utáni állapot, a (fenyegető) magzati hypoxia/acidosis, fájásgyengeség/elhúzódó szülés, relatív téraránytalanság, többes terhesség, hipertónia/praeeclampsia/HELLP-szindróma, medencevégű fekvés. Következtetések: A progresszív betegellátás következtében a klinikán a szülések kb. ötödrésze koraszülés, valamint számos súlyos terhespatológiai eset fordult elő, ennek ellenére a perinatalis statisztikai mutatókban – az utóbbi 17 év adatait elemezve – kedvező változások mutatkoznak, jelezvén a szülészeti és neonatológiai ellátás folyamatos szakmai fejlődését. Aim and methods: Authors report data from 48,794 deliveries in Semmelweis University, I. Department of Obstetrics and Gynecology, from January 1, 1990 to December 31, 2006. Data were analyzed based on their computer database, showing complexity of obstetrics, genetic counseling and neonatology. Results: In the last 17 years the delivery number is increasing, from 2,299 in 1990 to 3,861 in 2006. Early neonatal mortality rate is decreasing (22 infant deaths per 1,000 live births in 1990 compared with 6 in 2006). If we do not take those < or = 1,000 grams, intrauterine death outside the institute, and induction of labour because of malformation, perinatal mortality is very low, below 6/1,000 deliveries in the last 7 years, 2.8 in 2004, 1.8–1.9 in 2005 and 2006. Neonatal and infant mortality is also decreasing. There is an increase in the frequency of cesarean sections, 15–20% in 1990–1991, and approximately 35% in the last years. Main indications are previous cesarean section, threatened fetal hypoxia, dystocia, cephalopelvic disproportion, twin pregnancy, hypertension/praeeclampsia/HELLP syndrome, breech presentation. Conclusions: Because of the progressive system in obstetrics care in Hungary, in this leading institute approximately one fifth of the deliveries are preterm, furthermore they also have numerous severe pathological cases, though there are favorable changes in perinatal statistics in the last 17 years, showing the continuous improvement in obstetrical and neonatological care