Magnetic resonance imaging of the normal placenta.

The goal of this study was to provide a representative description of the normal placenta with contrast medium-free magnetic resonance imaging (MRI) in order to determine a standard of reference. One hundred consecutive singleton pregnancies were investigated by MRI without application of a contrast medium. The mean gestational age (GA) at the time of investigation was 29.5 weeks (range 19-40). Patients with suspected utero-placental insufficiency (UPI) or placental anomalies were excluded. Signal intensities were assessed and correlated with the respective GA. Antenatal MRI without contrast medium was able to depict placental status and morphological changes during gestation. A regular homogeneous structure was found in weeks 19-23. Subsequently, sporadic, slightly marked lobules appeared, which increased in number and markedness with ongoing gestation. Stratification of the lobules was observed after 36 weeks. The ratio of placental and amniotic fluid signal intensities decreased significantly with higher GA and with placental grading. MRI is well suited as an imaging method for the placenta. Our data may be used as a reference in the assessment of the placenta on MRI, and may have further clinical impact with respect to the determination of UPI.

Subtelomeric rearrangements as neutral genomic polymorphisms.

Submicroscopic chromosomal rearrangements affecting telomeres are important aetiological contributors to the development of mental retardation. Results from over 2,500 analysed patients with mental retardation demonstrated that about 5% have a subtelomeric aberration. However, some subtelomeric rearrangements have no phenotypic consequences. Due to the heterogeneity of such rearrangements and to the limited information about which monosomy or trisomy can be tolerated without phenotypic effect, conclusions about the association of a specific aberration and the phenotypical consequences are often hard to draw. We performed a study of subtelomeric aberrations with the aim to provide more insights into the understanding of such rearrangements as neutral genomic polymorphisms. We found two new polymorphisms: a duplication or triplication of the subtelomeric region of the long arm of chromosome 4 and a trisomy of the subtelomeric region of the short arm of chromosome 6 owing to a transposition to chromosome 22. These new data are presented and discussed in the context of the published literature.

Association of deletions of the chromosomal region 15q24-ter and diaphragmatic hernia: a new case and discussion of the literature.

OBJECTIVE: To provide new insights into how chromosomal aberrations affect fetal development, as well as for the counseling of parents in comparable situations, it is important to characterize and report the genotypes of fetuses with clinical anomalies. METHODS: Molecular cytogenetic analyses in a fetus with congenital diaphragmatic hernia (CDH). RESULTS: This report describes the first case of a deletion of the region q26.1-ter on chromosome 15 occurring as a de novo event associated with CDH. A detailed review of the literature provides further evidence of a functional association between deletions within the chromosomal region 15q24-ter and the development of CDH. CONCLUSIONS: The obtained data argue that detection of such a deletion in the region 15q24-ter associated with CDH likely predicts a poor prognosis. This report highlights the importance of giving special diagnostic attention to the chromosomal region 15q24-ter when prenatal ultrasound examination provides evidence of a CDH and warrants further research to identify genetic elements within the chromosomal region 15q24-ter related to the development of diaphragmatic hernia.

Prenatal diagnosis of tetrasomy 9p with Dandy-Walker malformation.

OBJECTIVES: To add to the knowledge of chromosomal abnormalities associated with Dandy-Walker malformation. METHODS: Molecular cytogenetic analyses of a chorionic villus sampling and of an amniocentesis of a fetus with Dandy-Walker malformation and abnormal somatic development. RESULTS: All cells examined showed a 47, XY, +idic(9p)(pter-->q12::q12-->pter) de novo karyotype. This report describes the fourth case of a tetrasomy 9p associated with Dandy-Walker malformation. CONCLUSIONS: This case, together with the three previously reported cases of an association with a tetrasomy 9p, indicate that this chromosomal aberration should be looked for when Dandy-Walker malformation is detected via prenatal ultrasonography.

Neurogenic cells in human amniotic fluid.

OBJECTIVE: The purpose of this study was to determine whether human amniotic fluid contains cells that harbor the potential to differentiate into neurogenic cells. STUDY DESIGN: Amniotic fluid cells (uncultivated or cultivated in standard or in neurogenic differentiation medium) were analyzed for morphologic neurogenic differentiation and for expression of cluster of differentiation 133 (marker for neuronal stem cells), nestin (neuronal progenitor cells), neurofilament (neurons), the p75 common neurotrophin receptor, the brain-derived neurotrophic factor and neurotrophin-3 and cyclic nucleotide phosphodiesterase (oligodendrocytes). RESULTS: The appearance of neurogenic cells was not detected in uncultivated cells, was sporadic after cultivation in standard medium but strongly increased in neurogenic differentiation medium, and was accompanied by the induction of the expression of the analyzed marker genes. CONCLUSION: For the first time, this study provides evidence that human amniotic fluid contains cells that express markers for neuronal stem and progenitor cells, which harbor the potential to differentiate into neurogenic cells.

Fetal and early postnatal magnetic resonance imaging--is there a difference?

AIM: To evaluate whether fetal magnetic resonance imaging (MRI) could replace early postnatal MRI in fetuses with central nervous system (CNS) anomalies. METHODS: Thirteen pregnancies presenting with fetal CNS anomalies were investigated using MRI. Indications included ventriculomegaly combined with additional CNS anomaly (n=5), isolated ventriculomegaly (n=2), arachnoid cyst (n=2), holoprosencephaly (n=1), complex malformation syndrome (n=1), Dandy walker malformation (n=1) and midline cyst (n=1). Early postnatal MRI followed within the first six weeks of life. RESULTS: Investigation with early postnatal MRI confirmed the fetal MRI diagnosis in all cases. Investigation with postnatal MRI presented additional information in two cases. However, there was no change in patient care. CONCLUSIONS: Fetal MRI should replace early postnatal MRI in infants with CNS anomalies.

Patient with partial trisomy 9q and learning disability but no pyloric stenosis.

Partial trisomy of the long arm of chromosome 9 represents a very rare and heterogeneous group of chromosomal aberrations. Associated clinical features include learning disability and pyloric stenosis. We present the first patient to be reported with a duplication of the chromosome region 9q22.1-->q33. The patient (female, age 17 years) presented with growth retardation, microcephaly, facial dysmorphia, oesophageal atresia, aortic stenosis, ventricular septal defect, atrial septal defect II, hypothyroidism, and learning disability, but no pyloric stenosis. A review of all cases of partial trisomy 9q reported in the literature demonstrates that learning disability is a characteristic feature of this group of chromosomal aberrations. However, there are cases of duplications of the same chromosome 9 material, with and without pyloric stenosis. This study provides new information for future genetic counselling, especially in cases of prenatal diagnosis of partial trisomy 9q.

Longitudinal observation of antenatally detected congenital lung malformations (CLM): natural history, clinical outcome and long-term follow-up.

OBJECTIVE: The objective of the study is to present longitudinal observations in antenatally detected congenital lung malformations (CLM), particularly pulmonary sequestration (PS) and cystic adenomatoid malformation (CAM). METHODS: Fetuses found to have a CLM on prenatal ultrasound (US) were included in this study and followed up until delivery. In all newborns radiographs and computerized tomography (CT) studies of the thorax were performed. Surgical procedures included sequesterectomy, lobectomy, segmentectomy, and non-anatomic resection. Based on prenatal US findings, intrauterine course, postpartum chest radiographs and CT scans, as well as clinical signs and surgical findings patients were divided into six groups. RESULTS: Over a period of 6 years, routine prenatal US revealed suggestion of CLM in a series of 35 consecutive fetuses. In six cases pregnancy was terminated or the fetuses suffered fetal demise. Another four fetuses became symptomatic in utero when sequential scanning revealed hydrops, hydrothorax, and enlargement of cysts or polyhydramnios. Three cases in this group received serial therapeutic amniocentesis and serial puncture of either the hydrothorax or intrapulmonary cysts. After postpartum treatment in the intensive care unit surgical procedures were performed uneventfully and confirmed the diagnosis of CAM, PS or hybrid type lesions. In 11 patients US findings were considered to demonstrate spontaneous resolution of the lesion, but disappearance without sequelae could be confirmed only in six infants. Five infants were shown to have persistent CLM on postpartum CT scans. These infants underwent resection of the lesion within the first year of life. In 11 fetuses CLM were continuously demonstrated during pregnancy with only slight changes in size and structure. Postpartum the infants were asymptomatic and were subjected to a systematic plan of diagnostic work-up and treatment. Surgery in these infants revealed a large number of hybrid type lesions (n=5). In three infants, the primary diagnosis of PS or CAM had to be corrected during the diagnostic and therapeutic work-up. CONCLUSION: CLM are diagnosed antenatally with an increasing frequency and are shown to be quite different from previously applied concepts. The expected clinical outcome is far better than thought to be possible.

Oct-4-expressing cells in human amniotic fluid: a new source for stem cell research?

BACKGROUND: It is the hope of investigators and patients alike that in future the isolation of pluripotent human stem cells will allow the establishment of therapeutic concepts for a wide variety of diseases. A major aim in this respect is the identification of new sources for pluripotent stem cells. Oct-4 is a marker for pluripotent human stem cells so far known to be expressed in embryonal carcinoma cells, embryonic stem cells and embryonic germ cells. METHODS: Cells from human amniotic fluid samples were analysed for mRNA expression of Oct-4, stem cell factor, vimentin and alkaline phosphatase via RT-PCR. Oct-4 protein expression was investigated by Western blot analysis and immunocytochemistry. Oct-4-positive cells were also analysed for the expression of cyclin A protein via double immunostaining. RESULTS: Performing RT-PCR, Western blot and immunocytochemical analyses revealed that in human amniotic fluid in the background of Oct-4-negative cells a distinct population of cells can be found, which express Oct-4 in the nucleus. Oct-4-positive amniotic fluid cell samples also express stem cell factor, vimentin and alkaline phosphatase mRNA. The Oct-4-positive amniotic fluid cells are actively dividing, proven by the detection of cyclin A expression. CONCLUSIONS: The results presented here suggest that human amniotic fluid may represent a new source for the isolation of human Oct-4-positive stem cells without raising the ethical concerns associated with human embryonic research.

Magnetic resonance imaging and ultrasound in the assessment of the fetal central nervous system.

Ultrasound is the screening modality of choice for evaluation of the fetal central nervous system (CNS). However, in cases of difficult diagnosis further fetal investigation is desirable. Due to ultrafast magnetic resonance imaging (MRI) techniques artifacts from fetal motions are minimized. MRI involves no exposure to radiation and hence appears to be safe. Due to the better soft tissue contrast, additional investigation by MRI may extend the sonographic diagnosis of fetal CNS-anomalies. Ultrasound and MRI are complementary imaging methods in the evaluation of the fetal CNS. The most important indications for ultrasound are screening for CNS anomalies and serial assessment of the dynamic of the disorder. The most important indications for fetal MRI are the "second opinion" and investigation by fetal MRI instead of postpartum MRI (especially in cases of planned postpartum intervention). In this article the indications and limitations of ultrasound and magnetic resonance imaging in the evaluation of the fetal CNS are discussed.

Absence of microdeletions in the azoospermia-factor region of the Y-chromosome in Viennese men seeking assisted reproduction.

PURPOSE: The azoospermia-factor region of the Y-chromosome is essential for spermatogenesis in humans. In the literature, a wide range is given for the frequency of microdeletions in this region. The purpose of this study was to evaluate our own population of patients. METHODS: During a two-year period at Vienna Medical School, all male patients (n = 383) seeking assisted reproduction were screened for microdeletions. Thirty-three men had azoospermia and 154 severe oligozoospermia. Genomic DNA was prepared from peripheral lymphocytes and polymerase chain reaction analysis of the azoospermia-factor region was performed using the Promega kit. RESULTS: No case tested positive for azoospermia-factor microdeletions. In all cases amplification of 18 non-polymorphic sequence tagged sites was obtained. CONCLUSIONS: Y-chromosome microdeletions do not seem to be an important factor for male infertility in our patients. This suggests that screening should be restricted to men with azoospermia or severe oligozoospermia only.

Brca1 regulates in vitro differentiation of mammary epithelial cells.

Murine Brca1 is widely expressed during development in different tissues. Why alterations of BRCA1 lead specifically to breast and ovarian cancer is currently not clarified. Here we show that Brca1 protein expression is upregulated during mammary epithelial differentiation of HC11 cells, during differentiation of C2C12 myoblasts into myotubes and during neuronal differentiation of N1E-115 cells. Ectopic overexpression of BRCA1 and downregulation of endogenous Brca1 expression specifically affect the regulation of mammary epithelial cell differentiation. Accelerated mammary epithelial cell differentiation upon high ectopic BRCA1 expression is not a consequence of the anti-proliferative capacity of this tumor suppressor and independent of functional p53. Overexpression of the BRCA1 variant lacking the large central exon 11 has no effects on mammary epithelial cell differentiation. These data provide new insights into the cellular role of Brca1.

A fetus with trisomy 9p and trisomy 10p originating from unbalanced segregation of a maternal complex chromosome rearrangement t(4;10;9).

Complex chromosome rearrangements are only rarely seen in constitutional karyotypes. A case of prenatally detected trisomy 9p with trisomy 10p originating from adjacent segregation of a maternal complex chromosome rearrangement is reported. Ultrasound examination at 18 weeks of gestation showed cleft lip palate, club feet, structural anomalies of the cerebellum and cystic kidneys. Cytogenetic analysis of amnion cells revealed a female fetus with 47,XX,+der(9). FISH analyses together with parental karyotyping demonstrated the fetal additional chromosome to originate from malsegregation of a maternal complex chromosomal rearrangement. The mother is carrier of a balanced translocation t(4;10;9) (q12; p11;q13). Postmortem examination of the fetus showed nose anomalies, cleft lip palate, low set ears, club feet, lung anomalies, cystic kidney and aplasia of the uterus. Reporting of such rare cases is important in order to enable this information to be used for genetic counselling in similar situations.