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  • 1
    Language: English
    In: Trends in Biochemical Sciences, 1996, Vol.21(9), pp.342-345
    Description: The human general co-factors werediscovered during biochemical fractionation of mammalian nuclear extracts in functional assays. They appear to act in concert with other coactivators that bind tightly to the TATA-binding protein and RNA polymerase II. Several co-factors have been shown to interact with general transcription factors, leading either to activation or repression of transcription. At least one subgroup of co-factors that enhance the effects of activators on transcription are DNA-binding proteins located in the chromatin. In fact, one co-factor, the repressor NC2, is structurally related to histones. The understanding of the molecular interplay of such components of the initiation complex in the chromatin—including general co-factors, other co-factors, general factors and activators—will be a major challenge in the future.
    Keywords: Biology
    ISSN: 0968-0004
    E-ISSN: 1362-4326
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  • 2
    In: Journal of Ultrasound in Medicine, November 2013, Vol.32(11), pp.1979-1986
    Description: OBJECTIVES: Patients with Hashimoto thyroiditis show structural changes of the thyroid that can be identified by a variety of sonographic criteria. We conducted this study to investigate whether there is a correlation between sonography and antibody activity and to assess the role of sonography in the diagnosis and follow-up of Hashimoto thyroiditis. In addition, we present a new classification system (termed the VESINC system [volume, echogenicity, sonographic texture, pseudonodular hypoechoic infiltration, nodules, and cysts]), which helps improve the clarity of sonographic findings.METHODS: The study included 223 consecutive patients with previously diagnosed Hashimoto autoimmune thyroiditis who attended the thyroid clinic of the German Armed Forces Central Hospital in Koblenz for follow-up examinations between 2006 and 2008. Laboratory tests were performed to measure the levels of free triiodothyronine, free thyroxine, thyrotropin, anti-thyroglobulin antibodies (TgAbs), and antithyroid peroxidase antibodies (TPOAbs). Sonography was performed according to a strict protocol. We then assessed whether a correlation existed between antibody activity and the 6 sonographic variables of the VESINC system.RESULTS: Hypoechogenicity, heterogeneity, and pseudonodular hypoechoic infiltration were associated with significantly higher TPOAb activity (P 〈 .001). There were no significant correlations between the other sonographic variables examined (cysts, nodules, and volume) or the biometric data with the TPOAb and TgAb levels. In addition, an assessment of TgAb levels did not show significant differences in correlations with any of the sonographic variables.CONCLUSIONS: Sonography is a noninvasive diagnostic imaging modality that provides information about the level of inflammatory activity. Markedly decreased echogenicity, heterogeneity, and multifocal pseudoinodular hypoechoic infiltration are indicative of a high level of inflammatory activity. The sonographic classification system presented here (VESINC system) can be a useful tool for comparing sonographic findings in a rapid and objective manner during follow-up of Hashimoto thyroiditis.
    Keywords: Anti-Thyroglobulin ; Anti-Thyroid Peroxidase ; Hashimoto Thyroiditis ; Sonographic Patterns ; Sonography
    ISSN: 0278-4297
    E-ISSN: 1550-9613
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  • 3
    Language: English
    In: Cell, 1994, Vol.78(3), pp.525-534
    Description: Our investigations of mammalian class II gene transcription resulted in identification, purification, and cloning of the corresponding cDNA of a cellular factor (p15) that mediates the effects of several distinct activators on transcription in vitro. Functional deletion analyses revealed a bipartite structure of p15 comprising an amino-terminal regulatory domain and a carboxy-terminal cryptic DNA-binding domain. We provide evidence that activity of p15 is controlled by protein kinases that target the regulatory domain. Structural and functional similarities, including sequence homology to domains essential for cofactor function, cofactor activity, promiscuity with respect to transcriptional activators, and interactions with components of the basal transcription machinery, relate this novel cellular cofactor to viral immediate-early transcriptional regulators.
    Keywords: Biology
    ISSN: 0092-8674
    E-ISSN: 1097-4172
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  • 4
    Language: English
    In: European Journal of Pediatrics, 2012, Vol.171(2), pp.337-345
    Description: Acute gastroenteritis (AGE) caused by rotavirus (RV) is a common disease among infants and toddlers, often leading to hospitalization and, in resource-poor countries, to death. However, little is known on specific complications of severe RV-positive (RV+) AGE and on the clinical course in chronically ill children. This was a retrospective analysis of data for children 〈5 years of age hospitalized due to AGE during six rotavirus seasons in three large German pediatric hospitals. The primary study end point was the incidence and type of complications in RV+ versus RV-negative (RV−) cases. A total of 6,884 episodes of AGE in hospitalized children aged 〈5 years were included in this analysis. Of the 4,880 stools tested for RV, 2,118 (43.4%) were RV+. Hypernatremia was significantly more common in RV+ AGE ( P  〈 0.001) and was associated with severe disease, need for intensive care treatment, and longer duration of hospitalization. Metabolic disorders, particularly hypoglycemia, were more common in RV+ AGE. In contrast, symptoms such as respiratory infections, neurological, and abdominal symptoms were more common in children with RV− AGE. Conclusions: hypernatremia is a specific complication of RV+ AGE. RV would therefore appear to be the cause of infant toxicosis, the traditional descriptive term for severe dehydration and clinical deterioration following AGE.
    Keywords: Acute gastroenteritis ; Rotavirus ; Hospitalized children ; Complications ; Hypernatremia
    ISSN: 0340-6199
    E-ISSN: 1432-1076
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  • 5
    In: The Journal of Bacteriology, 2009, Vol. 191(9), p.2934
    Description: Stenotrophomonas maltophilia is an opportunistic, highly resistant, and ubiquitous pathogen. Strains have been assigned to genogroups using amplified fragment length polymorphism. Hence, isolates of environmental and clinical origin predominate in different groups. A multilocus sequence typing (MLST) scheme was developed using a highly diverse selection of 70 strains of various ecological origins from seven countries on all continents including strains of the 10 previously defined genogroups. Sequence data were assigned to 54 sequence types (ST) based on seven loci. Indices of association for all isolates and clinical isolates of 2.498 and 2.562 indicated a significant linkage disequilibrium, as well as high congruence of tree topologies from different loci. Potential recombination events were detected in one-sixth of all ST. Calculation of the mean divergence between and within predicted clusters confirmed previously defined groups and revealed five additional groups. Consideration of the different ecological origins showed that 18 out of 31 respiratory tract isolates, including 12 out of 19 isolates from cystic fibrosis (CF) patients, belonged to genogroup 6. In contrast, 16 invasive strains isolated from blood cultures were distributed among nine different genogroups. Three genogroups contained isolates of strictly environmental origin that also featured high sequence distances to other genogroups, including the S. maltophilia type strain. On the basis of this MLST scheme, isolates can be assigned to the genogroups of this species in order to further scrutinize the population structure of this species and to unravel the uneven distribution of environmental and clinical isolates obtained from infected, colonized, or CF patients.
    Keywords: Blood Culture ; Clinical Isolates ; Recombination ; Linkage Disequilibrium ; Amplified Fragment Length Polymorphism ; Data Processing ; Trees ; Population Structure ; Pathogens ; Cystic Fibrosis ; Respiratory Tract ; Multilocus Sequence Typing ; Stenotrophomonas Maltophilia ; Cell Biology;
    ISSN: 0021-9193
    ISSN: 00219193
    E-ISSN: 10985530
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  • 6
    Language: English
    In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, January 2019, Vol.33(1), pp.1482-1495
    Description: Dysfunctional HDL is associated with coronary artery disease (CAD), but its effect on inflammation in vascular smooth muscle cells (VSMCs) in atherosclerosis is unknown. We investigated the effect of healthy human HDL and CAD-HDL on TNF-α-driven inflammation in VSMCs and examined whether HDL-associated sphingosine-1-phosphate (HDL-S1P) could modulate inflammation with the aim of designing novel HDL-based anti-inflammatory strategies. Healthy human HDL, human CAD-HDL, and mouse HDL were isolated by ultracentrifugation, S1P was measured by liquid chromatography-tandem mass spectrometry, and TNF-α-induced inflammation was characterized by gene expression and analysis of NF-κB-dependent signaling. Mechanisms of S1P interference with TNF-α were assessed by S1P receptor antagonists, mouse knockouts, and short interfering RNA. We observed that healthy HDL potently inhibited the induction of TNF-α-stimulated inflammatory genes, such as iNOS (inducible NO synthase) and MMP9 (matrix metalloproteinase 9), a process that was entirely dependent on HDL-S1P, as evidenced by loss-of-function using S1P-less HDL and mimicked by genuine S1P. Inhibition was based on suppression of TNF-α-activated Akt signaling resulting in reduced IkBαSer32 and p65Ser534 NF-κB phosphorylation based on a persistent phosphatase and tensin homolog activation by S1P through the S1P receptor 2. Intriguingly, S1P suppressed inflammation even hours after initial TNF-α stimulation. The anti-inflammatory effect of healthy HDL correlated with HDL-S1P content and was superior to that of CAD-HDL featuring lower HDL-S1P. Nevertheless, therapeutic loading of HDL with S1P completely restored the anti-inflammatory capacity of CAD-HDL and greatly boosted that of both healthy and CAD-HDL. Suppression of inflammation by HDL-S1P defines a novel pathophysiologic characteristic that distinguishes functional from dysfunctional HDL. The anti-inflammatory HDL function can be boosted by S1P-loading and exploited by S1P receptor-targeting to prevent and even turn off ongoing inflammation.-Keul, P., Polzin, A., Kaiser, K., Gräler, M., Dannenberg, L., Daum, G., Heusch, G., Levkau, B. Potent anti-inflammatory properties of HDL in vascular smooth muscle cells mediated by HDL-S1P and their impairment in coronary artery disease due to lower HDL-S1P: a new aspect of HDL dysfunction and its therapy.
    Keywords: Cad ; S1p ; Tnf-Α ; Vsmc ; Inflammation ; Coronary Artery Disease -- Metabolism ; Inflammation -- Prevention & Control ; Lipoproteins, HDL -- Metabolism ; Lysophospholipids -- Metabolism ; Muscle, Smooth, Vascular -- Metabolism ; Sphingosine -- Analogs & Derivatives
    ISSN: 08926638
    E-ISSN: 1530-6860
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  • 7
    In: Nature Genetics, 2006, Vol.38(11), p.1248
    Description: DMP1FGF23DMP1Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH) sub(2)D levels and suggesting that DMP1 may regulate FGF23 expression.
    Keywords: Dmp1 Protein ; Osteoblasts ; Plasma Levels ; Phosphaturia ; Phosphate ; Fibroblast Growth Factor 23 ; Hypophosphatemia ; Homeostasis ; Chromosome 4 ; Osteocytes ; Mutation ; Bone Matrix ; Human Genetics ; Genetics;
    ISSN: 1061-4036
    E-ISSN: 1546-1718
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  • 8
    Language: English
    In: Radiation and Environmental Biophysics, 2011, Vol.50(2), pp.313-323
    Description: Living in the vicinity of nuclear power plants (NPP) is discussed here in terms of adverse health effects. A prospective population-based cohort study was conducted to evaluate whether the prevalence of birth defects in the vicinity of NPPs is elevated and scrutinize a possible distance correlation. A birth cohort born to mothers living within 10 km of two selected NPPs (study region) was compared to a region without NPP (comparison region), and an active surveillance of all live births, stillbirths, and induced abortions in the defined regions was performed. Between 01/2007 and 02/2008, all newborns were examined by specially trained study paediatricians according to the protocols of the Birth Registry Mainz Model. The cohort consisted of 5,273 infants (90% completeness). The outcome measure was an infant with birth defect(s). The prevalence of infants with birth defects was 4.5% in the study region and 4.7% in the comparison region, which corresponds to a relative risk (RR) of 0.94 (lower 95% confidence level (CL): 0.76). Thus, the prevalence of birth defects in the regions surrounding NPPs was not increased compared to those of the comparison region. Adjustment for potential confounders did not substantially change the result (RR 0.90, lower 95% CL 0.73). The adjusted and unadjusted distance approach (1/distance in km) did not show any correlation to vicinity to a NPP ( p  = 0.38). Specifically, within the study region, the prevalence of birth defects showed no upward trend with decreasing distance. Birth defect prevalence and most descriptive parameters in the comparison region were identical to those in the Birth Registry Mainz Model.
    Keywords: Birth Defects -- Analysis ; Cancer Research -- Analysis ; Infants -- Analysis ; Nuclear Energy -- Analysis ; Nuclear Power Plants -- Analysis;
    ISSN: 0301-634X
    E-ISSN: 1432-2099
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  • 9
    In: Clinical Nuclear Medicine, 2000, Vol.25(11), pp.939-940
    Description: The authors describe two patients with unusual elevated uptake of fluorine-18 fluorodeoxyglucose (F-18 FDG) in the presence of nonmalignant diseases. Uptake of F-18 FDG as a result of granulomatous disease has been previously described. In one patient, we report a very high uptake F-18 FDG in the lungs, liver, and spleen in a 47-year-old woman as a result of sarcoidosis. The differential diagnosis included malignant lymphoma. F-18 FDG uptake has also been shown in inflammatory lesions. In the other case, high uptake of F-18 FDG in the epigastrium was evident in a 51-year-old man as a result of a foreign body (wooden toothpick), that had silently perforated the gastric wall.
    Keywords: Abdomen–Diagnostic Imaging ; Female–Diagnostic Imaging ; Fluorodeoxyglucose F18–Diagnostic Imaging ; Foreign Bodies–Diagnostic Imaging ; Humans–Diagnostic Imaging ; Male–Diagnostic Imaging ; Middle Aged–Diagnostic Imaging ; Radiopharmaceuticals–Diagnostic Imaging ; Sarcoidosis–Diagnostic Imaging ; Tomography, Emission-Computed–Diagnostic Imaging ; Radiopharmaceuticals ; Fluorodeoxyglucose F18;
    ISSN: 0363-9762
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  • 10
    Language: English
    In: Journal of Personality and Social Psychology, 2000, Vol.78(1), pp.105-119
    Description: Synthetic images of facial expression were used to assess whether judges can correctly recognize emotions exclusively on the basis of configurations of facial muscle movements. A first study showed that static, synthetic images modeled after a series of photographs that are widely used in facial expression research yielded recognition rates and confusion patterns comparable to posed photos. In a second study, animated synthetic images were used to examine whether schematic facial expressions consisting entirely of theoretically postulated facial muscle configurations can be correctly recognized. Recognition rates for the synthetic expressions were far above chance, and the confusion patterns were comparable to those obtained with posed photos. In addition, the effect of static versus dynamic presentation of the expressions was studied. Dynamic presentation increased overall recognition accuracy and reduced confusions between unrelated emotions.
    Keywords: Adult ; Analysis of Variance ; Emotions ; Facial Expression ; Female ; Humans ; Judgment ; Male ; Pattern Recognition, Visual ; Software ; Emotional Content ; Face Perception ; Facial Expressions ; Facial Muscles ; Motor Processes ; Computer Simulation ; Social Perception ; Social Perception & Cognition ; Perception of Emotion in Static Photos Vs Computer-Simulated Animations of Facial Muscle Movements, College Students ; Empirical Study ; Human ; Male ; Female ; Adulthood (18 Yrs & Older) ; Young Adulthood (18-29 Yrs) ; Article;
    ISSN: 0022-3514
    E-ISSN: 1939-1315
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