Béla Veszprémi

Myelination in the human hippocampal formation from midgestation to adulthood.

Myelination, one of the last steps of neuronal development, was examined in the human fetal and postnatal hippocampal formation using immunohistochemistry to detect a protein component of the myelin sheath, the myelin basic protein synthesized by oligodendroglial cells. Myelin basic protein‐immunoreactive oligodendroglial cells were first seen at the 20th gestational week in the fimbria fornicis and in the alveus. Between the 21st and 35th weeks, myelinated axons also appeared in the fimbria fornicis. At the age of 39 gestational weeks, short and thin myelinated fibers were present in the fimbria, in the alveus, and less so in the stratum oriens of the hippocampus, while the first oligodendroglial cells appeared in the stratum lacunosum‐moleculare and in the hilus. By the 2nd postnatal week myelinated fibers appeared in the stratum lacunosum‐moleculare of Ammons horn. At the 3rd month, myelination was strong in the alveus, moderate in the strata oriens, lacunosum‐moleculare and radiatum of Ammons horn, while only a small number of myelinated fibers were detected in the hilus. By the 5th month, the first oligodendroglial cells were detected in the molecular layer of the dentate gyrus. Myelination continued in the following years, particularly in the dentate gyrus, where even at the age of 11 years the density of myelinated fibers did not reach the adult level. It appears that the first myelinated axons belong to the long‐projecting large hippocampal pyramidal cells and/or to their subcortical and cortical afferents. The sequence of myelination follows the known developmental pattern of hippocampal afferent and efferent pathways, and the prolonged myelination might be a factor in the prolonged functional maturation of hippocampal circuitry.

Impaired myelination of the human hippocampal formation in Down syndrome

Myelination is considered as one of the last steps of neuronal development and is essential to the physiologically matured function of afferent and efferent pathways. In the present study, myelin formation was examined in the human fetal, postnatal and adult hippocampal formation in Down syndrome and in age‐matched controls with immunohistochemistry detecting a protein component of the myelin sheath, the myelin basic protein synthesized by oligodendroglial cells.

Ontogeny of calbindin immunoreactivity in the human hippocampal formation with a special emphasis on granule cells of the dentate gyrus

Calbindin (CB) is a calcium‐binding protein that is present in principal cells as well as in interneurons of the hippocampal formation of various species including humans. Studies with transgenic mice revealed that CB is essential for long‐term potentiation and synaptic plasticity which are the cellular basis of learning and memory. In a previous study we have shown that CB expression in granule cells of the dentate gyrus correlates with the functional maturation of the hippocampal formation in the rat.

Unaltered development of the archi- and neocortex in prematurely born infants: genetic control dominates in proliferation, differentiation and maturation of cortical neurons

The development of cerebral cortex includes highly organized, elaborate and long-lasting series of events, which do not come to an end by the time of birth. Indeed, many developmental events continue after the 40th postconceptual week resulting in a long morphological, behavioral and cognitive development of children. Premature birth causes an untimely dramatic change in the environment of the human fetus and often results in serious threats for life. Cognitive abilities of prematurely born children vary, but a correlation between cognitive impairment and the time of birth is evident. In this study we review the morphological evidence of cortical maturation in preterm and full-term infants. Various aspects of postnatal cortical development including cell proliferation and maturation of neurons in the temporal archi- and neocortex are discussed and compared in preterm infants and age-matched full-term controls. Our results suggest that cell proliferation and maturation are not influenced by the preterm delivery. In contrast, the perinatal decrease of the number of Cajal-Retzius cells might be regulated by a mechanism that is affected by preterm birth. We demonstrate that cognitive deficiencies of the prematurely born infants cannot be explained with light microscopically observed alteration of proliferation and maturation of neurons.

Possible association of first and high birth order of pregnant women with the risk of isolated congenital abnormalities in Hungary – a population-based case-matched control study

OBJECTIVE In epidemiological studies at the estimation of risk factors in the origin of specified congenital abnormalities in general birth order (parity) is considered as confounder. The aim of this study was to analyze the possible association of first and high (four or more) birth order with the risk of congenital abnormalities in a population-based case-matched control data set. STUDY DESIGN The large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities included 21,494 cases with different isolated congenital abnormality and their 34,311 matched controls. First the distribution of birth order was compared of 24 congenital abnormality groups and their matched controls. In the second step the possible association of first and high birth order with the risk of congenital abnormalities was estimated. Finally some subgroups of neural-tube defects, congenital heart defects and abdominal walls defects were evaluated separately. RESULTS A higher risk of spina bifida aperta/cystica, esophageal atresia/stenosis and clubfoot was observed in the offspring of primiparous mothers. Of 24 congenital abnormality groups, 14 had mothers with larger proportion of high birth order. Ear defects, congenital heart defects, cleft lip± palate and obstructive defects of urinary tract had a linear trend from a lower proportion of first born cases to the larger proportion of high birth order. Birth order showed U-shaped distribution of neural-tube defects and clubfoot, i.e. both first and high birth order had a larger proportion in cases than in their matched controls. CONCLUSIONS Birth order is a contributing factor in the origin of some isolated congenital abnormalities. The higher risk of certain congenital abnormalities in pregnant women with first or high birth order is worth considering in the clinical practice, e.g. ultrasound scanning.

Rapid diagnosis of fetal chromosomal abnormalities by fluorescence in situ hybridization

INTRODUCTION In the course of the Down-screening protocol there are possibilities today for rapid diagnosis of aneuploidies among high-risk pregnancies identified by non-invasive screening tests, however, the diagnostic value of these molecular genetic tests are debated. AIM OF THE STUDY In this prospective study, data about the reliability of one of the rapid tests, namely; interphase fluorescence in situ hybridization (int-FISH) was to be gathered by the authors. METHODS For the period between May 2002 and September 2006 all of the 1279 fetal sample were examined both with int-FISH and full karyotyping. RESULTS Extra or absent signal was detected in 47 cases (3.7%) (trisomy 21 in 32, various other numerical abnormalities in 15 cases). All of these numerical aberrations were confirmed by metaphase analysis without false positivity or negativity. In 19 cases the finding of int-FISH was negative, however, full karyotyping disclosed abnormalities (in 12 of these 19 cases, the abnormality was balanced). Only 4 of the 1279 fetuses (0.3%) (3 small extra marker chromosomes, 1 de novo unbalanced translocation) were to be found, who would have been born with phenotypical abnormalities without metaphase analysis (2 of them had suspect ultrasound signs). CONCLUSION Although more analysis are needed, based on the results of this study it is to be concluded that rapid molecular genetic methods like int-FISH might be accepted as a diagnostic tests of fetal aneuploidy, if its use were restricted to high risk pregnancies identified by advanced maternal age and non-invasive maternal screening only. However, full karyotyping is needed in cases with familial translocation and abnormal 2nd trimester ultrasound signs.

Sex ratio of congenital abnormalities in the function of maternal age: A population‐based study

Maternal age effect is well‐known in the origin of numerical chromosomal aberrations and some isolated congenital abnormalities (CAs). The sex ratio (SR), i.e. number of males divided by the number of males and females together, of most CAs deviates from the SR of newborn population (0.51). The objective of this analysis was to evaluate the possible association of maternal age with the SR of isolated CAs in a population‐based large dataset of the Hungarian Case‐Control Surveillance of Congenital Abnormalities, 1980–1996. First, SR of 24 CA entities/groups was estimated in 21 494 patients with isolated CA. In the next step SR of different maternal age groups was compared to the mean SR of the given CA‐groups. The SR of four CA‐groups showed some deviation in certain maternal age groups. Cases with anencephaly had female excess in young mothers (<25 years). Cases with skulls CAs particularly craniosynostosis had a male excess in cases born to women over 30 years. Two other CA groups (cleft lip ± palate and valvar pulmonic stenosis within the group of right‐sided obstructive defect of heart) had significant deviation in SR of certain maternal age groups from the mean SR, but these deviations were not harmonized with joining age groups and thus were considered as a chance effect due to multiple testing. In conclusion, our study did not suggest that in general SR of isolated CAs might be modified by certain maternal age groups with some exception such as anencephaly and craniosynostosis.

Magzati kromoszóma-rendellenességek gyors diagnosztizálása interfázis fluoreszcens in situ hibridizációval@@@Rapid diagnosis of fetal chromosomal abnormalities by fluorescence in situ hybridization

INTRODUCTION In the course of the Down-screening protocol there are possibilities today for rapid diagnosis of aneuploidies among high-risk pregnancies identified by non-invasive screening tests, however, the diagnostic value of these molecular genetic tests are debated. AIM OF THE STUDY In this prospective study, data about the reliability of one of the rapid tests, namely; interphase fluorescence in situ hybridization (int-FISH) was to be gathered by the authors. METHODS For the period between May 2002 and September 2006 all of the 1279 fetal sample were examined both with int-FISH and full karyotyping. RESULTS Extra or absent signal was detected in 47 cases (3.7%) (trisomy 21 in 32, various other numerical abnormalities in 15 cases). All of these numerical aberrations were confirmed by metaphase analysis without false positivity or negativity. In 19 cases the finding of int-FISH was negative, however, full karyotyping disclosed abnormalities (in 12 of these 19 cases, the abnormality was balanced). Only 4 of the 1279 fetuses (0.3%) (3 small extra marker chromosomes, 1 de novo unbalanced translocation) were to be found, who would have been born with phenotypical abnormalities without metaphase analysis (2 of them had suspect ultrasound signs). CONCLUSION Although more analysis are needed, based on the results of this study it is to be concluded that rapid molecular genetic methods like int-FISH might be accepted as a diagnostic tests of fetal aneuploidy, if its use were restricted to high risk pregnancies identified by advanced maternal age and non-invasive maternal screening only. However, full karyotyping is needed in cases with familial translocation and abnormal 2nd trimester ultrasound signs.