[DEGUM grade I quality standards in obstetric ultrasound diagnosis during the 19th-22nd week of pregnancy].
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Female↗
Biomedical subjects
R Bald
Publications and source records attributed to R Bald.
[DEGUM Level III recommendation for "follow-up" ultrasound examination (= DEGUM Level II) in the 11 - 14 week period of pregnancy].
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Female↗
Pulmonary atresia with intact ventricular septum and right coronary artery to right ventricle fistula detected in utero.
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Coronary Vessels↗
The specific hydrolysis of HIV-1 TAR RNA element with the anti-TAR hammerhead ribozyme: structural and functional implications.
The main transcriptional regulator of the human immunodeficiency virus is the Tat protein, which recognises and binds to a fragment RNA at the 5' end of viral mRNA, named transactivation response element (TAR) RNA. Extensive mutagenesis studies have shown that a region of TAR RNA important for Tat binding involves a set of nucleotides surrounding a characteristic UCU nucleotide bulge. The specific Tat-TAR complex formation enhances the rate of transcription elongation but inhibition of that interaction prevents the human immunodeficiency virus type 1 (HIV-1) replication. If so, a possibility of virus inactivation would be a site specific degradation of the TAR RNA element. To break down and inactivate TAR RNA, we designated the anti-hammerhead (HH) ribozyme to cleave nucleosides within the bulge. We showed for the first time the new type of the AUC hammerhead ribozyme, which hydrolyses specifically the TAR RNA element at C8 nucleotide in the bulge (C24 in the standard TAR RNA numbering). The cleavage reaction has broad magnesium requirements. Mn and particularly Ca are less efficient. Argininamide interferes with the cleavage of TAR RNA induced by the ribozyme. These results have two implications; (i) structural, where the HIV-1 TAR RNA element in solution occurs in equilibrium of only two forms, one of which, a double stranded RNA, meets structural requirements for ribozyme pairing and cleavage, and (ii) functional, the HH ribozyme can be explored for an inactivation of HIV-1 through the TAR RNA element deintegration.
Arginine↗
Concentrations of thrombopoietin and interleukin-11 in the umbilical cord blood of patients with fetal alloimmune thrombocytopenia.
The objective of this study is to determine whether the fetus compensates for fetal alloimmune thrombocytopenia (FAITP) by increasing serum concentrations of thrombopoietin (TPO) and interleukin-11 (IL-11). TPO and IL-11 concentrations were measured in cord blood sera of 12 neonates with FAITP, and 35 preterm and 25 term controls. TPO concentrations in the 12 patients (median 129 pg/mL, range 73 to 325 pg/mL) were similar to those of 35 healthy preterm neonates (median 183 pg/mL, range 71 to 290 pg/mL) and the 25 term controls (median 180 pg/mL, range 93 to 302 pg/mL), although the platelet counts were significantly lower in FAITP. TPO concentrations did not correlate with the platelet counts, platelet nadir after birth, or time to recovery of normal platelet count. IL-11 reached detectable concentrations only in four patients with FAITP (median 54 pg/mL). After birth, these patients had a more rapid recovery of the platelet count. Cord blood serum concentrations of TPO are not significantly elevated in FAITP and do not predict the severity of the thrombocytopenia. Elevated IL-11 may signal a more rapid platelet recovery in FAITP.
Fetal Blood↗
Fetal serum concentrations of cystatin C and beta2-microglobulin as predictors of postnatal kidney function.
OBJECTIVES: Cystatin C and beta(2)-microglobulin are established serum markers of renal function in children and adults. In contrast to creatinine, diaplacental exchange is minimal. The aim of the study was to establish reference values in fetal serum and to test their efficiency in predicting postnatal kidney function. STUDY DESIGN: This was a prospective noninterventional study measuring cystatin C and beta(2)-microglobulin by particle-enhanced immunoturbidimetry in excess serum from 129 cordocenteses performed in 84 fetuses. Reference intervals (mean +/- 1.96 SD) were calculated in a subgroup of 54 fetuses without evidence of kidney disease, and these reference values were evaluated in 75 sera from 55 fetuses. RESULTS: Mean cystatin C was 1.66 +/- 0.202 mg/L (upper limit 2.06), and mean beta(2)-microglobulin was 4.25 +/- 0.734 mg/L. Unlike cystatin C, beta(2)-microglobulin decreased significantly with gestational age so that the upper reference limit was 7.19-0.052 x gestational age in weeks. beta(2)-Microglobulin had higher sensitivity (90.0% vs 63.6%) and cystatin C a higher specificity (91.8% vs. 85.5%) for the prediction of impaired renal function; diagnostic efficiency was equal (87.6% vs. 86.1%). Fetuses with impaired renal function at birth or who were aborted for renal malformations had higher cystatin C concentrations than those in a control group. beta(2)-Microglobulin was increased only in fetuses who were aborted. CONCLUSION: Fetal serum cystatin C and beta(2)-microglobulin concentrations may be useful predictors of postnatal kidney function.
Cordocentesis↗
Intrauterine management of fetal parvovirus B19 infection.
OBJECTIVES: The aim of our study was to determine the outcome of pregnancies after intrauterine management of fetal parvovirus B19 infection. DESIGN: Retrospective study. SUBJECTS: A total of 37 cases of maternofetal parvovirus B19 infection, 35 of which were associated with hydrops fetalis, were referred to our tertiary level center between 1989 and 1996. With regard to fetal hydrops, no apparent cause other than parvovirus B19 infection was found in any patient. METHODS: In all patients, cordocentesis was performed to assess the degree of fetal anemia. When anemia was present, cordocentesis was followed by intrauterine transfusion with packed red cells into the umbilical vein. Further management depended on the degree of fetal anemia and gestational age and included follow-up fetal blood sampling/transfusion as well as ultrasound examinations as deemed appropriate. RESULTS: Packed red cell transfusion was performed in 30 patients with significant fetal anemia (Z-score 1.6-7.8 below the mean for gestational age). The fetal hemoglobin values ranged from 2.1 to 9.6 g/dl. Serum levels of platelets in the transfusion group were 9-228 x 10(9)/l with Z-scores in the range of < 1 to 3.8 below the mean. During treatment and follow-up, there were five intrauterine deaths (13.5%), one neonatal death (2.7%) and 31 live births (83.8%). CONCLUSIONS: Fetal parvovirus infection can lead to marked anemia and hydrops formation. Cordocentesis allows precise assessment of fetal anemia which can then be corrected by intravenous transfusion. Under this regimen, the outcome proved favorable in the majority of fetuses, even those that were severely anemic.
Anemia↗
Fetal cord blood as an alternative source of hematopoietic progenitor cells: immunophenotype, maternal cell contamination, and ex vivo expansion.
The present study was performed to investigate the character of hematopoietic progenitor cells in fetal cord blood (CB). Thirty blood samples from fetuses at a median of 24 weeks of gestation (range 19-29) and 30 neonatal CB samples were analyzed for their immunophenotype by three-color flow cytometry and examined for the presence of female cells by fluorescence in situ hybridization (FISH). We tested the effects of different cytokine combinations (rhIL-1beta, rhIL-3, rhIL-6, rh erythropoietin [rhEPO], rhGM-CSF plus rhSCF, and rhSCF plus rhflt3-ligand) on the differentiation of 100 CD34+-enriched neonatal CB cells for up to 21 days. Ex vivo expansion of 32 unselected fetal blood samples cells was performed in the presence of rhSCF and rhflt3-ligand. The percentage of CD34+ cells in fetal blood was significantly higher compared with neonatal CB (1.24%+/-0.82% versus 0.33%+/-0.18%, p = 0.0001) and inversely correlated with the age of gestation. The contamination of fetal and neonatal CB with maternal cells was low (1.72%+/-0.89%, range 1.0%-4.0%). By using rhflt3-ligand we were able to expand committed progenitor cells while maintaining cells with stem cell function. The use of expanded fetal immature progenitors might have implications for in utero transplantation and autologous gene therapy.
Cell Culture Techniques↗
Crystal structure of domain E of Thermus flavus 5S rRNA: a helical RNA structure including a hairpin loop.
The synthetic RNA fragment 5'-CUGGGCGG(GCGA)CCGCCUGG (nucleotides in parentheses indicate the loop region) corresponds to the natural sequence of domain E from nucleotides 79-97 of the Thermus flavus 5S rRNA including a hairpin loop. The RNA structure determined at 3.0 A and refined to an R-value of 24.1% also represents the first X-ray structure GNRA tetraloop. The loop is in distinctly different conformation from other GNRA tetraloops analyzed by NMR. The conformation of the two molecules in the asymmetric unit is influenced and stabilized by specific intermolecular contacts. The structural features presented here give evidence for the ability of RNA molecules to adapt to specific environments.
Base Sequence↗
[Fetal plasma erythropoietin concentration during intrauterine transfusion therapy in isoimmunohemolytic anemia due to rhesus incompatibility].
PURPOSE: Prenatal plasma concentrations of erythropoietin in fetuses with Rh disease should contribute information to the clinical course and therapeutic control of this disease. METHOD: Fetal plasma erythropoietin (Epo) and haemoglobin (Hb) concentrations were measured in 145 umbilical venous blood samples of 30 fetuses with Rh disease at 20 to 38 weeks' gestation. RESULTS: Both Epo and Hb concentrations were independent of the gestational age in red blood cell-isoimmunised pregnancies. The Hb concentration correlated significantly with Epo concentration without intrauterine transfusion (IUT) (r = -0.519, p = 0.005) and after IUT (i = -0.212, p = 0.01). A haemoglobin deficit of 3 g/dl at 20 weeks' gestation increased to 6 g/dl at 38 weeks' gestation in spite of IUT (p = -0.354, p < 0.001). CONCLUSION: Even with IUT, Epo concentrations increase with gestational age during these pregnancies. This is due to increasing Hb deficits indicating fetal hypoxia which might be prevented by increasing volumes of transfusion.
Adult↗
Fetal Rhesus D genotyping on amniocytes in alloimmunised pregnancies using fluorescence duplex polymerase chain reaction.
OBJECTIVE: 1. To establish the reliability of fetal amniocyte Rhesus D (RhD) genotyping using fluorescence duplex polymerase chain reaction (PCR) and 2. to assess the potential clinical impact on management of alloimmunised pregnancies. DESIGN: Multicentre observational study. SETTING: Four departments of obstetrics and gynaecology in Germany. METHODS: Fourty-four amniotic fluid samples were obtained by amniocentesis from a retrospective group of 27 RhD alloimmunised pregnancies and 15 samples from 14 women treated prospectively. Two RhD gene specific fragments (exon 7 and 10) were amplified using two separate fluorescence duplex PCR assays, and laser detected in an automated DNA sequence analyser. RESULTS: Amplification of the Rh gene sequences was successful in all samples. PCR at the two RhD gene regions resulted in complete concordance. Genotyping correctly predicted the RhD status of all fetuses serotyped (n = 41). After intrauterine transfusions, PCR identified the RhD type of two fetuses more accurately than serotyping. Earlier knowledge of a negative RhD status would have rendered unnecessary 12 amniocenteses in four fetuses of the retrospective study group, and prevented further invasive testing in one fetus treated prospectively. In the latter group, women with a positive fetal RhD genotype underwent intensive prenatal care including serial invasive monitoring and intrauterine treatment. CONCLUSIONS: Fetal RhD genotyping of amniocytes is a reliable technique with the potential to improve routine management of alloimmunised pregnant women.
Amniocentesis↗
Complete identification of nonbridging phosphate oxygens involved in hammerhead cleavage.
Phosphorothioate interference analysis is suited for the rapid identification of structurally and functionally important phosphate groups. Previous interference studies, however, have been limited to the analysis of pro-Rp phosphate oxygens. We employed solid-phase oligonucleotide synthesis and modification interference analysis to investigate either of the nonbridging phosphate oxygens within the hammerhead ribozyme. Two novel sites of Sp phosphorothioate interference were identified at positions A6 and U16.1. The results from interference experiments were confirmed by single phosphorothioate substitutions at sites of interest. Metal rescue experiments revealed that direct metal ion coordination occurs in the functional ribozyme only at the site of cleavage and at the pro-Rp oxygen of position Ag. The new approach may be generally useful in rapidly evaluating the functional importance of phosphate groups in nucleic acids.
Cations, Divalent↗
[Intrauterine transfusion in fetal alloimmunothrombocytopenia: comparison of maternal and fetal weight-adjusted IgG therapy with exclusive fetal thrombocyte transfusion].
Fetal alloimmune thrombocytopenia is caused by maternal immunization against a fetal platelet antigen and transplacental transfer of the antibody into the fetal circulation. Since 10-20% of the fetuses or newborns are threatened by intracranial hemorrhages, early management is required. Fetal blood sampling should be started between the 20th and 22nd week of gestation to assess fetal phenotype and platelet count. Different concepts to elevate the fetal platelet count have been discussed: maternal intravenous immunoglobulins, fetal intravenous immunoglobulins, or only repeated fetal platelet transfusions. Our investigations suggested that platelet transfusions in short intervals appear to be the only effective regimen to increase platelet counts in thrombocytopenic fetuses at risk.
Birth Weight↗
Initial analysis of 750 MHz NMR spectra of selective 15N-G,U labelled E. coli 5S rRNA.
The overall folding of an RNA molecule is reflected in its base pairing pattern. The identification of that pattern provides a first step towards the determination of the structure of an RNA molecule. We show that the application of heteronuclear NMR methods at 750 MHz to E. coli 5S rRNA (120 nucleotides) selectively labelled with 15N in guanine and uridine allows observation of base pairing patterns for a larger RNA molecule. We also present evidence that the fold of the E-domain of the 5S rRNA (nt 79-97) as a contiguous part of the 5S rRNA and as an isolated molecule is virtually the same.
Base Composition↗
Therapy with intravenous immunoglobulin G (ivIgG) during pregnancy for fetal alloimmune (HPA-1a(Zwa)) thrombocytopenic purpura.
We have evaluated the effect of maternal intravenous immunoglobulin G (ivIgG) treatment on platelet counts in fetal alloimmune thrombocytopenia. Seven patients were studied. All of them were multiparous women who had been immunized against the HPA-1a antigen during previous pregnancies and had given birth to at least one severely thrombocytopenic infant. In this study, umbilical blood collection was performed first at the 20th week of gestation and repeated 2-13 times (mean 6 times), depending on the degree of fetal thrombocytopenia. Fetal platelet counting was combined with intrauterine transfusion of 20-30 ml of HPA-1a-negative platelet concentrates to prevent bleeding following umbilical cord puncture. Initial fetal platelet counts ranged from 10,000 to 91,000 per microliters. Maternal treatment with ivIgG (1 g per kg body weight; mean dose 70 g) was given once a week over 7 weeks. In five of seven cases, the basal platelet count did not rise and in two of these cases, it decreased during maternal ivIgG treatment. In one fetus, the baseline platelet count increased from 10,000 to 35,000 per microliters during ivIgG, and in another fetus from 23,000 to 64,000 per microliters. Our observations suggest that ivIgG has no definite benefit for fetal alloimmune thrombocytopenia. Since platelet counts can be very low, careful fetal monitoring by umbilical blood sampling is required. Frequent platelet transfusions in short intervals may be necessary to increase platelet counts in extremely thrombocytopenic fetuses.
Antigens, Human Platelet↗
Mirror-image RNA that binds D-adenosine.
A 58-mer L-RNA ligand that binds to naturally occurring D-adenosine with a dissociation constant of 1.7 microM in solution was identified from a combinatorial library employing mirror-design. The corresponding D-RNA ligand shows identical binding affinity to L-adenosine. Reciprocal chiral specificity was also evident from ligand discrimination; the binding affinity of the L-RNA ligand for D-adenosine was 9000-fold greater than its affinity for L-adenosine and vice versa. While the D-RNA ligand was rapidly degraded in human serum, the L-RNA ligand displayed an extraordinary stability. This indicates the potential application of specifically designed L-RNA ligands as stable monoclonal antibody analogues and the development of highly stable L-ribozymes.
Adenosine↗
Mirror-design of L-oligonucleotide ligands binding to L-arginine.
The high affinity and selectivity of nucleic acid ligands have clearly demonstrated that RNA can be targeted to a variety of molecules. In practice, however, the use of unmodified aptamers is impeded by the low stability of RNA in biological fluids. Here we describe the mirror-design of a stable 38-mer L-oligoribonucleotide ligand that binds to L-arginine. This L-RNA ligand was also able to bind to a short peptide containing the basic region of the human immunodeficiency virus type-1 Tat-protein. The L-RNA ligand displayed the expected stability in human serum. These findings may contribute to the identification of novel diagnostics and pharmaceuticals.
Amino Acid Sequence↗
[Fetal weight-adjusted intrauterine IgG therapy in neonatal alloimmune thrombocytopenia].
Fetal alloimmune thrombocytopenia is caused by materno-fetal transfer of platelet antibodies. Since the thrombocytopenic fetus is threatened by intracranial hemorrhage, prenatal observation and, if necessary, treatment is required. However, the benefit of therapeutic options, including intravenous IgG (ivIgG), platelet transfusions or fetal IgG transfusions is still controversial. In this study we have evaluated the effect of intrauterine IgG and intraumbilical platelet transfusions on fetal platelet counts. All patients were multiparous women who were immunized against the Zwa antigen during previous pregnancies and had given birth to at least one severely thrombocytopenic infant. First umbilical blood was sampled at the 20th week of gestation. Fetal treatment of IgG was given, on av erage, over 9 weeks. In all cases, fetal IgG levels rose significantly whereas platelet counts did not increase following fetal IgG treatment. We conclude that fetal IgG infusions have no detectable effect on fetal allo-immune thrombocytopenia. Since platelet counts can be very low as early as 20 weeks of gestation, careful fetal monitoring by umbilical blood sampling is essential. Platelet transfusions in short intervals appear to be the only effective regimen to increase platelet counts in thrombocytopenic fetuses at risk.
Adult↗