A complex phenotype with cystic renal disease.
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Adolescent↗
Biomedical subjects
R Ullmann
Publications and source records attributed to R Ullmann.
Characterization of a de novo complex chromosome rearrangement (CCR) involving chromosomes 2 and 12, associated with mental retardation and impaired speech development.
We report on a currently six-year-old patient with a de novo complex chromosome rearrangement (CCR) involving chromosomes 2 and 12. A translocation 2;12 that appeared to be reciprocal after standard banding turned out to be a complex event with seven breaks after molecular cytogenetic analyses. Array CGH analysis showed no imbalances at the breakpoints but revealed an additional microdeletion of about 80 kb on chromosome 11. The same deletion was also present in the phenotypically normal father. The patient showed relatively mild mental retardation, defined mainly as impaired speech development (orofacial dyspraxia) and psychomotor retardation. In addition, mild dysmorphic facial features like hypertelorism, a prominent philtrum and down-turned corners of the mouth were observed. We narrowed down all breakpoint regions to about 100 kb, using a panel of mapped bacterial artificial chromosome (BAC) clones for fluorescence in situ hybridization (FISH). BACs spanning or flanking all seven breakpoints were identified and no chromosomal imbalances were found consistent with the array CGH results. Our investigations resulted in the following karyotype: 46,XY,t(2;12)(2pter-->2p25.3::2p23.3-->2p25.2::2p23.3-->2p14::2q14.3-->2p14::2q14.3-->2q14.3::12q 12-->12qter;12pter-->12q12::2p25.3-->2p25.2::2q14.3-->2qter).
Child↗
Impact of low copy repeats on the generation of balanced and unbalanced chromosomal aberrations in mental retardation.
Low copy repeats (LCRs) are stretches of duplicated DNA that are more than 1 kb in size and share a sequence similarity that exceeds 90%. Non-allelic homologous recombination (NAHR) between highly similar LCRs has been implicated in numerous genomic disorders. This study aimed at defining the impact of LCRs on the generation of balanced and unbalanced chromosomal rearrangements in mentally retarded patients. A cohort of 22 patients, preselected for the presence of submicroscopic imbalances, was analysed using submegabase resolution tiling path array CGH and the results were compared with a set of 41 patients with balanced translocations and breakpoints that were mapped to the BAC level by FISH. Our data indicate an accumulation of LCRs at breakpoints of both balanced and unbalanced rearrangements. LCRs with high sequence similarity in both breakpoint regions, suggesting NAHR as the most likely cause of rearrangement, were observed in 6/22 patients with chromosomal imbalances, but not in any of the balanced translocation cases studied. In case of chromosomal imbalances, the likelihood of NAHR seems to be inversely related to the size of the aberration. Our data also suggest the presence of additional mechanisms coinciding with or dependent on the presence of LCRs that may induce an increased instability at these chromosomal sites.
Chromosome Aberrations↗
Novel rearrangement of chromosome band 22q11.2 causing 22q11 microdeletion syndrome-like phenotype and rhabdoid tumor of the kidney.
The 22q11.2 microdeletion syndrome is the most frequent microdeletion syndrome in humans, yet its genetic basis is complex and is still not fully understood. Most patients harbor a 3-Mb deletion (typically deleted region [TDR]), but occasionally patients with atypical deletions, some of which do not overlap with each other and/or the TDR, have been described. Microduplication of the TDR leads to a phenotype similar, albeit not identical, to the deletion of this region. Here we present a child initially suspected of having 22q11 microdeletion syndrome, who in addition developed a fatal malignant rhabdoid tumor of the kidney. Detailed cytogenetic and molecular analyses revealed a complex de novo rearrangement of band q11 of the paternally derived chromosome 22. This aberration exhibited two novel features. First, a microduplication of the 22q11 TDR was associated with an atypical 22q11 microdeletion immediately telomeric of the duplicated region. Second, this deletion was considerably larger than previously reported atypical 22q11 deletions, spanning 2.8 Mb and extending beyond the SMARCB1/SNF5/INI1 tumor suppressor gene, whose second allele harbored a somatic frameshift-causing sequence alteration in the patient's tumor. Two nonallelic homologous recombination events between low-copy repeats (LCRs) could explain the emergence of this novel and complex mutation associated with the phenotype of 22q11 microdeletion syndrome.
Chromosome Deletion↗
Is high-grade adenomatous hyperplasia an early bronchioloalveolar adenocarcinoma?
Atypical adenomatous hyperplasia (AAH) is a probable forerunner of bronchioloalveolar carcinoma (BAC) and pulmonary adenocarcinoma (AC) of mixed type. The present study analysed four low-grade AAHs, 13 high-grade AAHs, two BACs, nine mixed ACs, and one squamous cell carcinoma derived from 13 patients using comparative genomic hybridization. The average number of chromosomal aberrations was 1.2 in low-grade AAH, 9.6 in high-grade AAH, and 12.5 in AC. A high degree of overlap of genetic changes was found in high-grade AAH, BAC, and AC within individual patients. The high number of aberrations and the degree of shared aberrations found in high-grade AAH and AC raises questions about the separation of these two entities. In addition, in view of the monoclonal origin of multiple foci within the same patient, AAH may not be a precursor of AC in some cases, but rather may represent intraepithelial spread.
Adenocarcinoma, Bronchiolo-Alveolar↗
Loss of heterozygosity on chromosome arm 11q in lung carcinoids.
Neuroendocrine lung tumors such as typical carcinoid, atypical carcinoid, small-cell lung carcinoma, and large-cell neuroendocrine carcinoma represent a variable group with different biologic characteristics and unclear genetical relationships. We investigated the pattern of allelic loss on chromosome arm 11q in 20 sporadic carcinoid tumors of the lung using 10 microsatellite markers. Loss of heterozygosity was found in 13 of 20 tumors. In 5 of 9 typical carcinoids, 3 distinct regions of allelic loss were identified: 11q13.1 (D11S1883), 11q14.3-11q21 (D11S906), and 11q25 (D11S910). Atypical carcinoids showed loss of heterozygosity at 4 different regions: the first, most proximal region at 11q13 between markers PYGM and D11S937; the second at 11q14.3-11q21 (D11S906); and the third and fourth defined by markers D11S939 (11q23.2-23.3) and D11S910 (11q25). However, the region 11q13 harboring the MEN1 gene was more frequently affected in atypical carcinoids (7 of 11) than in typical carcinoids (2 of 9). The high rate of allelic losses within chromosomal region 11q13 in atypical carcinoids emphasizes the importance of this region for tumor development. We also recognized that more aggressive atypical carcinoids defined by high mitotic counts, vascular invasion, and/or organ metastasis are combined with increased allelic losses. HUM PATHOL 32:333-338.
Adult↗
Chromosomal aberrations in a series of large-cell neuroendocrine carcinomas: unexpected divergence from small-cell carcinoma of the lung.
Large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) are high-grade neuroendocrine tumors of the lung. Despite different morphologic appearances, loss of heterozygosity and oncogene studies on LCNEC to date suggest genetic similarities. We analyzed 13 LCNEC and 5 mixed SCLC/LCNEC tumors by comparative genomic hybridization and subsequently compared our results with previously published data on 32 SCLCs. Comparison with SCLC showed several shared chromosomal aberrations, specifically losses of 3p, 4q, 5q, and 13q and gains of 5p. However, these aberrations are no special feature of neuroendocrine lung tumors but can also be found in other high-grade lung carcinomas. From this point of view, genetic similarities of LCNEC and SCLC are less important than the nonrandom changes that differ between these 2 tumor types. A gain of 3q observed in 66% of all SCLCs was detected only once in the LCNEC group. In contrast to the pure LCNEC, all mixed types with a SCLC component had a gain of 3q. Gains of 6p occurred more frequently in LCNEC. Deletions of 10q, 16q, and 17p were less frequent in LCNEC than in SCLC.
Biomarkers, Tumor↗
Comparative genomic hybridization and cytogenetic analysis in a bronchial adenoma: three clones with different chromosomal aberrations.
Classical chromosomal analysis and comparative genomic hybridization (CGH) were performed in a tubular bronchial gland adenoma. Trisomy of chromosomes 2, 11, 18 and 20 and clonal loss of Y were found in cultured cells derived from two different kryotubes; this was also confirmed by CGH from one of these tubes. Cells from two other tubes, investigated by CGH only, showed gains and losses of parts of chromosome 11q in one, and in the second additional gain of the distal portion of 9q and 17q, respectively. CGH analysis of tumor DNA extracted from paraffin-embedded sections showed no chromosomal imbalances. In cell culture growth the advantage of specific clones probably altered the clone distribution. This study highlights the risk of cytogenetic analysis based on cell cultures only.
Adenoma↗
The tail domain of myosin M catalyses nucleotide exchange on Rac1 GTPases and can induce actin-driven surface protrusions.
Members of the myosin superfamily play crucial roles in cellular processes including management of the cortical cytoskeleton, organelle transport and signal transduction. GTPases of the Rho family act as key control elements in the reorganization of the actin cytoskeleton in response to growth factors, and other functions such as membrane trafficking, transcriptional regulation, growth control and development. Here, we describe a novel unconventional myosin from Dictyostelium discoideum, MyoM. Primary sequence analysis revealed that it has the appearance of a natural chimera between a myosin motor domain and a guanine nucleotide exchange factor (GEF) domain for Rho GTPases. The functionality of both domains was established. Binding of the motor domain to F-actin was ATP-dependent and potentially regulated by phosphorylation. The GEF domain displayed selective activity on Rac1-related GTPases. Overexpression, rather than absence of MyoM, affected the cell morphology and viability. Particularly in response to hypo-osmotic stress, cells overexpressing the MyoM tail domain extended massive actin-driven protrusions. The GEF was enriched at the tip of growing protuberances, probably through its pleckstrin homology domain. MyoM is the first unconventional myosin containing an active Rac-GEF domain, suggesting a role at the interface of Rac-mediated signal transduction and remodeling of the actin cytoskeleton.
Actins↗
Transport of C(4)-dicarboxylates in Wolinella succinogenes.
C(4)-dicarboxylate transport is a prerequisite for anaerobic respiration with fumarate in Wolinella succinogenes, since the substrate site of fumarate reductase is oriented towards the cytoplasmic side of the membrane. W. succinogenes was found to transport C(4)-dicarboxylates (fumarate, succinate, malate, and aspartate) across the cytoplasmic membrane by antiport and uniport mechanisms. The electrogenic uniport resulted in dicarboxylate accumulation driven by anaerobic respiration. The molar ratio of internal to external dicarboxylate concentration was up to 10(3). The dicarboxylate antiport was either electrogenic or electroneutral. The electroneutral antiport required the presence of internal Na(+), whereas the electrogenic antiport also operated in the absence of Na(+). In the absence of Na(+), no electrochemical proton potential (delta p) was measured across the membrane of cells catalyzing fumarate respiration. This suggests that the proton potential generated by fumarate respiration is dissipated by the concomitant electrogenic dicarboxylate antiport. Three gene loci (dcuA, dcuB, and dctPQM) encoding putative C(4)-dicarboxylate transporters were identified on the genome of W. succinogenes. The predicted gene products of dcuA and dcuB are similar to the Dcu transporters that are involved in the fumarate respiration of Escherichia coli with external C(4)-dicarboxylates. The genes dctP, -Q, and -M probably encode a binding-protein-dependent secondary uptake transporter for dicarboxylates. A mutant (DcuA(-) DcuB(-)) of W. succinogenes lacking the intact dcuA and dcuB genes grew by nitrate respiration with succinate as the carbon source but did not grow by fumarate respiration with fumarate, malate, or aspartate as substrates. The DcuA(-), DcuB(-), and DctQM(-) mutants grew by fumarate respiration as well as by nitrate respiration with succinate as the carbon source. Cells of the DcuA(-) DcuB(-) mutant performed fumarate respiration without generating a proton potential even in the presence of Na(+). This explains why the DcuA(-) DcuB(-) mutant does not grow by fumarate respiration. Growth by fumarate respiration appears to depend on the function of the Na(+)-dependent, electroneutral dicarboxylate antiport which is catalyzed exclusively by the Dcu transporters. Dicarboxylate transport via the electrogenic uniport is probably catalyzed by the DctPQM transporter and by a fourth, unknown transporter that may also operate as an electrogenic antiporter.
Anaerobiosis↗
Unbalanced chromosomal aberrations in neuroendocrine lung tumors as detected by comparative genomic hybridization.
Typical and atypical carcinoids (TC, ATC) and small (SCLC) and large cell neuroendocrine carcinomas (LCNEC) constitute the spectrum of neuroendocrine lung tumors. Chromosomal aberrations have not been studied in LCNEC and only rarely in carcinoids. Only SCLCs have been investigated frequently for chromosomal aberrations. We compared three typical and four atypical carcinoids, one atypical carcinoid/SCLC mixed type, three SCLC, and three LCNEC for chromosomal gains and losses using comparative genomic hybridization. Typical carcinoids showed either no changes or only few chromosomal gains. Atypical carcinoids appeared genetically heterogeneous: One case had no aberrations, and three cases had few aberrations; two of them showed a deletion of 11q. SCLC and LCNEC were characterized by many gains and losses, especially similar changes of 3p, 5q, 5p, and 13q. Although ATC resemble LCNEC morphologically, there were no similarities at the genetic level. We have found a reciprocal relationship of prognosis and the amount of aberrations. TCs and ATCs with few chromosomal changes have the best prognosis, whereas SCLCs and LCNECs were generally characterized by a great amount of aberrations and worst prognosis. There was no unbalanced aberration common in all types of neuroendocrine tumors of the lung.
Carcinoid Tumor↗
Nanofabrication of Small Copper Clusters on Gold(111) Electrodes by a Scanning Tunneling Microscope
The use of scanning tunneling microscopy in an electrochemical environment as a tool for the nanoscale modification of gold electrodes was demonstrated. Small copper clusters, typically two to four atomic layers in height, were precisely positioned on a gold(111) electrode by a process in which copper was first deposited onto the tip of the scanning tunneling microscope, which then acted as a reservoir from which copper could be transferred to the surface during an appropriate approach of the tip to the surface. Tip approach and position were controlled externally by a microprocessor unit, allowing the fabrication of various patterns, cluster arrays, and "conducting wires" in a very flexible and convenient manner.
Journal Article↗
[Street traffic noise and stress experience].
Interpreting a sociological study in the city of Erfurt the results of a written interrogation of noise annoyance of a representative random sample of inhabitants are shown and selected characteristics both of the annoyed and the nonannoyed inhabitants are compared. From noise level measurements a proposal for a traffic noise threshold limit has been derived that corresponds to the requirement for calm. Moreover, moderators have been investigated which interfere with the degree of annoyance; health complaints of both groups of the interrogated individuals were compared. It could be shown, that a written interrogation of inhabitants of a territory is able to deliver sufficiently exact information concerning noise annoyance.
Germany, East↗
[New aspects of the traffic noise problem in the inner city area].
As a result of a sociological-oriented noise study in the city of Erfurt specific intracity noise problems are analysed via their effects. The authors deal with the expectation of calm of people living in different areas of the city, with the relevance of effect of the two usual evaluation levels Leq and Lmax for noise by running traffic, with noise decrease by sound attenuation improvements, and with the subjective and objective evaluation of an industrial front ventilation element. Moreover, the effects of traffic noise on inhabitants before and after significant traffic reduction are shown.
Automobiles↗
[Some public health effects of agricultural methane gas plants on the environment].
Several big agricultural fermentation plants for producing of "biogas" are in operation in the GDR. Problems of distances to other objects, utilisation of methane and storage of liquid manure (slurry) are discussed. Some results of experiments about the immissions in the environment are demonstrated. They have point out, that the emissions of microorganisms and viruses cannot be demonstrated in a distance of more than about 200 meters. It is the most important hygienic acknowledge, that the distance of organoleptic observation is always greater than the epidemiologic or sanitary one. Therefore the production of energy by anaerobic fermentation of liquid manure and sewage sludge seems to be an useful way from hygienic point of view.
Agriculture↗
[Salmonella occurrence in the Erfurt district].
Annually in the district Erfurt 7 percent of all reported diarrhoeal illnesses were microbiologically identified. Salmonellosis, shigellosis and Campylobacter infections dominate. Between 1986 and 1987 a strong increase of salmonellosis were registered, which was caused by S. enteritidis in 70% of the cases and associated with the consumption of eggs or other products, which were manufactured from eggs contaminated with S. enteritidis.
Animals↗
[Assessment of virus contamination in rivers of a drinking water reservoir and effects on the water quality of the reservoir].
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Adenoviruses, Human↗
[Health problems at cosmetic, foot care and beauty salons].
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Beauty Culture↗