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RarA is a widely conserved protein proposed to be involved in recombination-dependent replication. We present a cell biological approach to identify functional connections between RarA and other proteins using single molecule tracking. We found that 50% of RarA molecules were static, mostly close to replication forks and likely DNA-bound, while the remaining fraction was highly dynamic throughout the cells. RarA alternated between static and dynamic states. Exposure to H2O2 increased the fraction of dynamic molecules, but not treatment with mitomycin C or with methyl methanesulfonate, which was exacerbated by the absence of RecJ, RecD2, RecS and RecU proteins. The ratio between static and dynamic RarA also changed in replication temperature-sensitive mutants, but in opposite manners, dependent upon inhibition of DnaB or of DnaC (pre)primosomal proteins, revealing an intricate function related to DNA replication restart. RarA likely acts in the context of collapsed replication forks, as well as in conjunction with a network of proteins that affect the activity of the RecA recombinase. Our novel approach reveals intricate interactions of RarA, and is widely applicable for in vivo protein studies, to underpin genetic or biochemical connections, and is especially helpful for investigating proteins whose absence does not lead to any detectable phenotype.

All living cells have a large number of proteins that are anchored with one transmembrane helix in the cytoplasmic membrane. Almost nothing is known about their spatiotemporal organization in whole cells. Here we report on the localization and dynamics of one representative, the pH sensor and transcriptional regulator CadC in Escherichia coli. Fluorophore-tagged CadC was detectable as distinct cluster only when the receptor was activated by external stress, which results in DNA-binding. Clusters immediately disappeared under non-stress conditions. CadC variants that mimic the active state of CadC independent of environmental stimuli corroborated the correlation between CadC clustering and binding to the DNA, as did altering the number or location of the DNA-binding site(s) in whole cells. These studies reveal a novel diffusion-and-capture mechanism to organize a membrane-integrated receptor dependent on the DNA in a rod-shaped bacterium., Brameyer et al. identify a diffusion-and-capture mechanism responsible for the localization of the membrane integrated receptor and transcriptional activator CadC in E. coli. They find that external stress activates CadC, resulting in DNA-binding and cluster formation in the cytoplasmic membrane.

Bacillus subtilis possesses 2 DNA translocases that affect late stages of chromosome segregation: SftA separates nonsegregated DNA prior to septum closure, while SpoIIIE rescues septum-entrapped DNA. We provide evidence that SftA is associated with the division machinery via a stretch of 47 amino acids within its N-terminus, suggesting that SftA is recruited by protein-protein interactions with a component of the division machinery. SftA was also recruited to mid-cell in the absence of its first 20 amino acids, which are proposed to contain a membrane-binding motif. Cell fractionation experiments showed that SftA can be found in the cytosolic fraction, and to a minor degree in the membrane fraction, showing that it is a soluble protein in vivo. The expression of truncated SftA constructs led to a dominant sftA deletion phenotype, even at very low induction rates of the truncated proteins, indicating that the incorporation of nonfunctional monomers into SftA hexamers abolishes functionality. Mobility shift experiments and surface plasmon binding studies showed that SftA binds to DNA in a cooperative manner, and demonstrated low ATPase activity when binding to short nucleotides rather than to long stretches of DNA.

Like many bacteria, Bacillus subtilis possesses two DNA translocases that affect chromosome segregation at different steps. Prior to septum closure, nonsegregated DNA is moved into opposite cell halves by SftA, while septum-entrapped DNA is rescued by SpoIIIE. We have used single-molecule fluorescence microscopy and tracking (SMT) experiments to describe the dynamics of the two different DNA translocases, the cell division protein FtsA and the glycolytic enzyme phosphofructokinase (PfkA), in real time. SMT revealed that about 30% of SftA molecules move through the cytosol, while a fraction of 70% is septum bound and static. In contrast, only 35% of FtsA molecules are static at midcell, while SpoIIIE molecules diffuse within the membrane and show no enrichment at the septum. Several lines of evidence suggest that FtsA plays a role in septal recruitment of SftA: an ftsA deletion results in a significant reduction in septal SftA recruitment and a decrease in the average dwell time of SftA molecules. FtsA can recruit SftA to the membrane in a heterologous eukaryotic system, suggesting that SftA may be partially recruited via FtsA. Therefore, SftA is a component of the division machinery, while SpoIIIE is not, and it is otherwise a freely diffusive cytosolic enzyme in vivo . Our developed SMT script is a powerful technique to determine if low-abundance proteins are membrane bound or cytosolic, to detect differences in populations of complex-bound and unbound/diffusive proteins, and to visualize the subcellular localization of slow- and fast-moving molecules in live cells. IMPORTANCE DNA translocases couple the late events of chromosome segregation to cell division and thereby play an important role in the bacterial cell cycle. The proteins fall into one of two categories, integral membrane translocases or nonintegral translocases. We show that the membrane-bound translocase SpoIIIE moves slowly throughout the cell membrane in B. subtilis and does not show a clear association with the division septum, in agreement with the idea that it binds membrane-bound DNA, which can occur through cell division across nonsegregated chromosomes. In contrast, SftA behaves like a soluble protein and is recruited to the division septum as a component of the division machinery. We show that FtsA contributes to the recruitment of SftA, revealing a dual role of FtsA at the division machinery, but it is not the only factor that binds SftA. Our work represents a detailed in vivo study of DNA translocases at the single-molecule level.

Single-particle (molecule) tracking (SPT/SMT) is a powerful method to study dynamic processes in living bacterial cells at high spatial and temporal resolution. We have performed single-molecule imaging of early DNA double-strand break (DSB) repair events during homologous recombination in the model bacterium Bacillus subtilis. Our findings reveal that DNA repair centres arise at all sites on the chromosome and that RecN, RecO and RecJ perform fast, enzyme-like functions during detection and procession of DNA double strand breaks, respectively. Interestingly, RecN changes its diffusion behavior upon induction of DNA damage, from a largely diffusive to a DNA-scanning mode, which increases efficiency of finding all sites of DNA breaks within a frame of few seconds. RecJ continues being bound to replication forks, but also assembles at many sites on the nucleoid upon DNA damage induction. RecO shows a similar change in its mobility as RecN, and also remains bound to sites of damage for few hundred milliseconds. Like RecN, it enters the nucleoid in damaged cells. Our data show that presynaptic preparation of DSBs including loading of RecA onto ssDNA is highly rapid and dynamic, and occurs throughout the chromosome, and not only at replication forks or only at distinct sites where many breaks are processes in analogy to eukaryotic DNA repair centres.

DnaA is a conserved key regulator of replication initiation in bacteria, and is homologous to ORC proteins in archaea and in eukaryotic cells. The ATPase binds to several high affinity binding sites at the origin region and upon an unknown molecular trigger, spreads to several adjacent sites, inducing the formation of a helical super structure leading to initiation of replication. Using FRAP analysis of a functional YFP-DnaA allele in Bacillus subtilis, we show that DnaA is bound to oriC with a half-time of 2.5 seconds. DnaA shows similarly high turnover at the replication machinery, where DnaA is bound to DNA polymerase via YabA. The absence of YabA increases the half time binding of DnaA at oriC, showing that YabA plays a dual role in the regulation of DnaA, as a tether at the replication forks, and as a chaser at origin regions. Likewise, a deletion of soj (encoding a ParA protein) leads to an increase in residence time and to overinitiation, while a mutation in DnaA that leads to lowered initiation frequency, due to a reduced ATPase activity, shows a decreased residence time on binding sites. Finally, our single molecule tracking experiments show that DnaA rapidly moves between chromosomal binding sites, and does not arrest for more than few hundreds of milliseconds. In Escherichia coli, DnaA also shows low residence times in the range of 200 ms and oscillates between spatially opposite chromosome regions in a time frame of one to two seconds, independently of ongoing transcription. Thus, DnaA shows extremely rapid binding turnover on the chromosome including oriC regions in two bacterial species, which is influenced by Soj and YabA proteins in B. subtilis, and is crucial for balanced initiation control, likely preventing fatal premature multimerization and strand opening of DnaA at oriC., Author summary Initiation of replication is a key event in the cell cycle of all living cells, and is mediated by the ATPase DnaA in bacteria, and by ORC proteins in eukaryotic cells. DnaA binds to several high affinity binding sites at the origin region of replication (oriC) on the bacterial chromosome, triggers the unwinding of the DNA duplex nearby, and additionally supports loading of the DNA helicase, which in turn leads to the establishment of the DNA replication machinery. How the binding of DnaA to oriC and the triggering of duplex opening are regulated is under extensive investigation. Using two different fluorescence microscopy techniques, we show that DnaA binding and unbinding to oriC is very rapid in two bacterial species and occurs in the range of few seconds. Moreover, DnaA binds to several additional sites on the chromosome, but with an even shorter binding half-time than at oriC: average residence time throughout the chromosome is about 200 ms, as determined by single molecule microscopy. In the absence of two negative regulators, YabA and Soj, DnaA in Bacillus subtilis binds longer to oriC and to other sites on the chromosome, accompanied by a higher frequency of initiation per cell cycle, whereas the expression of a DnaA mutant protein that shows even faster exchange rates results in decreased initiation frequency. Our data reveal that DnaA exchanges rapidly at oriC, and that tight regulation of turnover is important for proper initiation control. We also show that YabA has a dual role, a) in tethering DnaA to the replication machinery and restricting its mobility within the cell and b) in increasing DnaA turnover at oriC, both of which activities reduce the risk of reinitiation during later stages in the cell cycle.

Conjugation activity of plasmid pLS20 from Bacillus subtilis subsp. natto is induced when cells are diluted into fresh medium and diminishes as cells enter into stationary-phase growth. Transcriptional profiling shows that during mid-exponential growth, more than 5% of the host genes are affected in the presence of the plasmid, in contrast to the minor changes seen in freshly diluted and stationary-phase cells. Changes occurred in many metabolic pathways, although pLS20 does not confer any detectable burden on its host cell, as well as in membrane and cell wall-associated processes, in the large motility operon, and in several other cellular processes. In agreement with these changes, we found considerable alterations in motility and enzyme activity and increased resistance against several different forms of stress in cells containing the plasmid, revealing that the presence of pLS20 has a broad impact on the physiology of its host cell and increases its stress resistance in multiple aspects. Additionally, we found that the lack of chromosomal gene yueB , known to encode a phage receptor protein, which is upregulated in cells containing pLS20, strongly reduced conjugation efficiency, revealing that pLS20 not only increases fitness of its host but also employs host proteins for efficient transfer into a new cell.

Summary To assess the diversity of total, denitrifying and N2-fixing bacteria in a nitrogen (N)-limited, acid forest soil, isolated DNA was analysed for the genes 16S rRNA, nosZ and nifH. Sequence information for these genes was obtained from clone libraries and from our TReFID computer program, which employs terminal restriction patterns for bacteria using multiple restriction enzymes. Both approaches indicated that Proteobacteria (α- and γ-groups) and Acidobacteria dominated. A comprehensive list of bacteria retrieved from this soil is provided and compared with literature data on the bacterial community compositions from other sites. The study indicated that the current PCR conditions with the primers employed allowed retrieval of only a portion of the bacteria occurring in soils. Massive treatment of a soil plot with NH4NO3 caused an increase in the N content, which was rapidly followed by an enhancement of carbon (C) content. Thus the C/N ratio stayed below 16.0 and the soil remained N-limited. This may explain why the bacterial diversity did not undergo drastic shifts as was tentatively inferred from the available data sets.

Objectives To assess at a population-based level the frequency with which severe structural congenital malformations are detected prenatally in Europe and the gestational age at detection, and to describe regional variation in these indicators. Methods In the period 1995–1999, data were obtained from 17 European population-based registries of congenital malformations (EUROCAT). Included were all live births, fetal deaths and terminations of pregnancy diagnosed with one or more of the following malformations: anencephalus, encephalocele, spina bifida, hydrocephalus, transposition of great arteries, hypoplastic left heart, limb reduction defect, bilateral renal agenesis, diaphragmatic hernia, omphalocele and gastroschisis. Results The 17 registries reported 4366 cases diagnosed with the 11 severe structural malformations and of these 2300 were live births (53%), 181 were fetal deaths (4%) and 1863 were terminations of pregnancy (43%); in 22 cases pregnancy outcome was unknown. The overall prenatal detection rate was 64% (range, 25–88% across regions). The proportion of terminations of pregnancy varied between regions from 15% to 59% of all cases. Gestational age at discovery for prenatally diagnosed cases was less than 24 weeks for 68% (range, 36–88%) of cases. There was a significant relationship between high prenatal detection rate and early diagnosis (P < 0.0001). For individual malformations, the prenatal detection rate was highest for anencephalus (469/498, 94%) and lowest for transposition of the great arteries (89/324, 27%). Termination of pregnancy was performed in more than half of the prenatally diagnosed cases, except for those with transposition of the great arteries, diaphragmatic hernia and gastroschisis, in which 30–40% of the pregnancies with a prenatal diagnosis were terminated. Conclusion European countries currently vary widely in the provision and uptake of prenatal screening and its quality, as well as the ‘culture’ in terms of decision to continue the pregnancy. This inevitably contributes to variation between countries in perinatal and infant mortality and in childhood prevalence and cost to health services of congenital anomalies. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.

The purpose of this study was to measure the spatially varying 31P MR signals in global and regional ischemic injury in the isolated, perfused rat heart. Chronic myocardial infarcts were induced by occluding the left anterior descending coronary artery eight weeks before the MR examination. The effects of acute global low-flow ischemia were observed by reducing the perfusate flow. Chemical shift imaging (CSI) with three spatial dimensions was used to obtain 31P spectra in 54-microl voxels. Multislice 1H imaging with magnetization transfer contrast enhancement provided anatomical information. In normal hearts (n = 8), a homogeneous distribution of high-energy phosphate metabolites (HEP) was found. In chronic myocardial infarction (n = 6), scar tissue contained negligible amounts of HEP, but their distribution in residual myocardium was uniform. The size of the infarcted area could be measured from the metabolic images; the correlation of infarct sizes determined by histology and 31P MR CSI was excellent (P < 0.006). In global low-flow ischemia (n = 8), changes of HEP showed substantial regional heterogeneity. Three-dimensional 31P MR CSI should yield new insights into the regionally distinct metabolic consequences of various forms of myocardial injury.

Conjugation is an efficient way for transfer of genetic information between bacteria, even between highly diverged species, and a major cause for the spreading of resistance genes. We have investigated the subcellular localization of several conserved conjugation proteins carried on plasmid pLS20 found in Bacillus subtilis . We show that VirB1, VirB4, VirB11, VirD2, and VirD4 homologs assemble at a single cell pole, but also at other sites along the cell membrane, in cells during the lag phase of growth. Bimolecular fluorescence complementation analyses showed that VirB4 and VirD4 interact at the cell pole and, less frequently, at other sites along the membrane. VirB1 and VirB11 also colocalized at the cell pole. Total internal reflection fluorescence microscopy showed that pLS20 is largely membrane associated and is frequently found at the cell pole, indicating that transfer takes place at the pole, which is a preferred site for the assembly of the active conjugation apparatus, but not the sole site. VirD2, VirB4, and VirD4 started to localize to the pole or the membrane in stationary-phase cells, and VirB1 and VirB11 were observed as foci in cells resuspended in fresh medium but no longer in cells that had entered exponential growth, although at least VirB4 was still expressed. These data reveal an unusual assembly/disassembly timing for the pLS20 conjugation machinery and suggest that specific localization of conjugation proteins in lag-phase cells and delocalization during growth are the reasons why pLS20 conjugation occurs only during early exponential phase.

Each year, more than 4500 pregnancies in the European Union are affected by neural tube defects (NTD). Unambiguous evidence of the effectiveness of peri conceptional folic acid in preventing the majority of neural tube defects has been available since 1991. We report on trends in the total prevalence of neural tube defects up to 2002, in the context of a survey in 18 European countries of periconceptional folic acid supplementation (PFAS) policies and their implementation. EUROCAT is a network of population-based registries in Europe collaborating in the epidemiological surveillance of congenital anomalies. Representatives from 18 participating countries provided information about policy, health education campaigns and surveys of PFAS uptake. The yearly total prevalence of neural tube defects including livebirths, stillbirths and terminations of pregnancy was calculated from 1980 to 2002 for 34 registries, with UK and Ireland estimated separately from the rest of Europe. A meta-analysis of changes in NTD total prevalence between 1989-1991 and 2000-2002 according to PFAS policy was undertaken for 24 registries. By 2005, 13 countries had a government recommendation that women planning a pregnancy should take 0.4 mg folic acid supplement daily, accompanied in 7 countries by government-led health education initiatives. In the UK and Ireland, countries with PFAS policy, there was a 30% decline in NTD total prevalence (95% CI 16-42%) but it was difficult to distinguish this from the pre-existing strong decline. In other European countries with PFAS policy, there was virtually no decline in NTD total prevalence whether a policy was in place by 1999 (2%, 95% CI 28% reduction to 32% increase) or not (8%, 95% CI 26% reduction to 16% increase). The potential for preventing NTDs by periconceptional folic acid supplementation is still far from being fulfilled in Europe. Only a public health policy including folic acid fortification of staple foods is likely to result in large-scale prevention of NTDs. (c) 2005 Elsevier Inc. All rights reserved.

To assess at a population-based level the frequency with which severe structural congenital malformations are detected prenatally in Europe and the gestational age at detection, and to describe regional variation in these indicators.In the period 1995-1999, data were obtained from 17 European population-based registries of congenital malformations (EUROCAT). Included were all live births, fetal deaths and terminations of pregnancy diagnosed with one or more of the following malformations: anencephalus, encephalocele, spina bifida, hydrocephalus, transposition of great arteries, hypoplastic left heart, limb reduction defect, bilateral renal agenesis, diaphragmatic hernia, omphalocele and gastroschisis.The 17 registries reported 4366 cases diagnosed with the 11 severe structural malformations and of these 2300 were live births (53%), 181 were fetal deaths (4%) and 1863 were terminations of pregnancy (43%); in 22 cases pregnancy outcome was unknown. The overall prenatal detection rate was 64% (range, 25-88% across regions). The proportion of terminations of pregnancy varied between regions from 15% to 59% of all cases. Gestational age at discovery for prenatally diagnosed cases was less than 24 weeks for 68% (range, 36-88%) of cases. There was a significant relationship between high prenatal detection rate and early diagnosis (P0.0001). For individual malformations, the prenatal detection rate was highest for anencephalus (469/498, 94%) and lowest for transposition of the great arteries (89/324, 27%). Termination of pregnancy was performed in more than half of the prenatally diagnosed cases, except for those with transposition of the great arteries, diaphragmatic hernia and gastroschisis, in which 30-40% of the pregnancies with a prenatal diagnosis were terminated.European countries currently vary widely in the provision and uptake of prenatal screening and its quality, as well as the "culture" in terms of decision to continue the pregnancy. This inevitably contributes to variation between countries in perinatal and infant mortality and in childhood prevalence and cost to health services of congenital anomalies.

Fur eine Fehlbildungserfassung gewinnt die pranatale Diagnostik zunehmend an Bedeutung, da fehlgebildete Feten auch bei terminierten Schwangerschaften in die Pravalenzberechnungen aufgenommen werden mussen. Deshalb wurden die Gynakologen in Sachsen-Anhalt, die eine erweiterte Ultraschalldiagnostik durchfuhren gebeten, Befunde zu Fehlbildungen und den jeweiligen Schwangerschaftsausgang mitzuteilen. Bis zum jetzigen Zeitpunkt wurden 201 Falle ausgewertet. Am haufigsten erfolgte mit 27% die Diagnosestellung in der 20./21. SSW, in immerhin 17% erst in der 28. SSW oder spater. 55,7% der Frauen trugen die Schwangerschaften nach der Fehlbildungsdiagnose aus, 29,4% der Frauen entschlossen sich zur vorzeitigen Beendigung der Schwangerschaft und in 14,9% war der Ausgang der Schwangerschaft nicht bekannt. Am haufigsten (20,4%) wurden Fehlbildungen der Nieren und ableitenden Harnwege diagnostiziert, gefolgt von ZNS-Fehlbildungen (15,9%). Chromosomenaberrationen wurden in 10,4% nachgewiesen und in 9,5% bestanden multiple congenitale Anomalien. Fehlbildungen des Herzens und der grosen Gefase traten in 6% auf. Die hauptsachlichste Indikation zur Ultraschallfeindiagnostik war in 11,4% das Alter der Frau, in 8% war in vorangegangenen Untersuchungen der Verdacht auf ein Nackenodem geausert worden und bei weiteren 8% bestand eine intrauterine Retardierung. Vorzeitig beendet wurden Schwangerschaften in 10% wegen Fehlbildungen des ZNS, in 8% wegen Chromosomenaberrationen und in 5,5% wegen multipler congenitaler Anomalien. Die Untersuchungen werden kontinuierlich fortgesetzt.

For the last 20 years the prophylactic effect of the vitamin folic acid against the occurrence of neural tube defects has been known but in Germany this fact has not been realized by the public. The recommendations by medical institutions fail, among other reasons, because a folic acid prescription by gynaecologists comes too late in the course of events, i.e., women go to the gynaecologist when pregnancy has already set in and it is too late for preventive measures. An effective folic acid prophylaxis must take place before the onset of pregnancy. Data from the regional surveillance of congenital anomalies of the German Federal State of Saxony-Anhalt and interviews with women in maternity, as well as gynaecologists, indicate that there is a substantial knowledge deficit concerning folic acid prophylaxis. In 1998, therefore, a working group was set up in Saxony-Anhalt. It comprises representatives from interested institutions and has the goal of rectifying the knowledge deficit of women of childbearing age by way of a broad-based campaign while making use of the results of regional congenital anomalies monitoring. A pharmaceutical company was enlisted for cost-free distribution of its folic acid product. Legal problems with the prescription drug laws, the law against unfair competitive practices, the advertising of medicaments law and the SGB V (social code) made it impossible to procure multivitamins containing folic acid free of charge for women wanting a child. A highly differentiated legislation has hitherto prevented an elementary improvement in prevention.

The epidemiological analysis of trisomy 21 presented for the new federal German state of Saxony-Anhalt describes trends and changes in the frequency of Down's syndrome and prevalences of the pregnancy outcomes including acceptance of prenatal diagnostic measures in the period from 1980 and with separate analysis for the period since reunification in 1990. The average prevalence in the entire period is 1.0 per 1000 births. In 1997, a prevalence of 1.7 per 1000 births was already observed. After 1990, there is an increase in the prevalence of conceptions with trisomy 21 whereas the prevalence of live births with Down's syndrome remained the same. The reasons for this are an increase in the age of the mothers and a broad acceptance of prenatal diagnostics. Ethical questions, that might for example reveal societal changes in the attitude to children with Down's syndrome have not been considered in the analysis, since this would require sociological investigations which cannot be carried out by the malformations register.

From 1980 to 1996 1.8% of all births died as a result of malformations during the first week of life. This rate has been declining significantly after 1992. Congenital malformations of the heart have increased significantly because of improved diagnostic methods. From 1980 to 1996 0.67/1000 of all children died of vitium cordis during the first week of life. From 1992 to 1996 this group of malformations increased the perinatal mortality rate by 0.4/1000. There is a decreased mortality rate of neural tube defects by 0.25/1000 1980 to 1986 and by 0.08/1000 1992 to 1996. Trisomy 21: the early mortality rate decreased from 0.07/1000 to 0.03/1000. The number of non-deceased children with Down's syndrome remains constant, even though 40 per cent of all cases with trisomy 21 were prenatal. 3 per cent of all malformed newborn died during the first week of life as a result of their congenital malformations. The possibility of primary prevention of malformations with folic acid has not been sufficiently utilised.

Periconceptional intake of folic acid is one of only few possibilities of preventing congenital malformations. We report on the update situation of applying folic acid and the effects on the prevalence of neural tube defects and oral clefts. The analysis is based on data of the malformation registry in Saxony-Anhalt. A common public campaign on the benefit of folic acid protection is presented.

Between 09/01/92 and 08/31/95 the Mainz model to register birth defects had been tested in the city of Magdeburg at the same time when the regional register instituted in 1980 was continued. The aim of this hospital-based model for the thorough registry of malformations in neonates is to examine all newborns born in hospitals using clinical and sonographical methods by experienced physicians according to a standardized scheme. Additional medical and social data were recorded. Data on live-and stillborn as well as spontaneous abortions older than the 16th gestational week and induced abortions following prenatal diagnosis were included. During the survey 5255 neonates were examined. The calculated percentage of major birth defects (by definition) was 7.8% and therefore higher than reported before. The experience with the Mainz model in the city of Magdeburg demonstrates, that this model is basically applicable to other centres. It is possible to obtain valid data on malformation frequencies in a defined population. Special attention has to be paid to certain conditions in the composition of hospital populations.

The Magdeburg Register of birth defects includes information on the incidence rate of neural tube defects (NTD) in the city of Magdeburg since 1980, and in the Regierungsbezirk (administrational district) since 1987. The average prevalence of NTD was 16.4 per 10,000 births in the city of Magdeburg, and 12 per 10,000 births in the surrounding counties. Besides of this significant difference between the city and counties, there are conspicuous variations from one year to the next. In 1987 the prevalence of NTD was about 27 per 10,000 births in the city of Magdeburg whereas the observed prevalence in the countryside was about 19 per 10,000 births. Different eating habits and/or increased teratogenic influences in the city may be considered as causes. In 1997 there was also a high rate of incidence of NTD in the city of Magdeburg--16.4 per 10,000 births. The incidence rate of NTD in the counties (about 10 per 10,000) births) is again lower than in the city. Because of these incidence rates, we may assume that the examined population is insufficiently protected by folic acid in the preconceptional stage.

Analysis of the Hamburg perinatal quality assurance programme shows a dramatic increase in congenital abnormalities of the bones, joints and muscles from 45.29 per 10,000 live births in 1990 to 106.32 in 1994. Comparisons with other perinatal quality assurance programme data reveal almost the same trend. In fact, there is no real increase in these specific congenital abnormalities, but there is an effect, which can be explained by the introduction of ultrasound hip screening in infancy signalling overdiagnostics due to the new technology. This example demonstrates that the perinatal quality assurance programme is a suitable instrument for registering congenital abnormalities and monitoring new technologies and interventions. These results support the proposal by the association of the leading state health officers (AGLMB) to use the already well-established quality assurance programmes which are analysed on state level for a systematic nation-wide documentation and "surveillance" of congenital abnormalities. In addition, it becomes clear that surveillance, understood as a further development of health reporting, offers an opportunity to effect both an assessment and a better orientation in respect of health policies.

Since there is no nationwide system and documentation of congenital malformations in Germany, local health authorities were not able to respond to the question of an increase in limb reduction defects occurring on the coast of Northern Germany. Previously, such an increase had been reported by the media in England in 1994. For limb reduction defects, the feasibility and efficiency of the so-called "Magdeburg-model" for monitoring congenital malformations is demonstrated. This model provides data on reduction defects for analysing regional (Magdeburg versus Magdeburg county) and temporal trends, and for classifying reduction defects. The data are based on a population of 214.901 births (lifebirths and stillbirths) and on the analysis of 64 cases with limb reduction defects over a 15-year period. In 1992-1994 in Magdeburg and Magdeburg county no increase of limb reduction defects and other indicator malformations were found.