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  • 1
    Online Resource
    Online Resource
    Wiley ; 2000
    In:  American Journal of Medical Genetics Vol. 95, No. 2 ( 2000-11-13), p. 157-160
    In: American Journal of Medical Genetics, Wiley, Vol. 95, No. 2 ( 2000-11-13), p. 157-160
    Type of Medium: Online Resource
    ISSN: 0148-7299 , 1096-8628
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2000
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    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Elsevier BV ; 2000
    In:  Developmental Brain Research Vol. 125, No. 1-2 ( 2000-12), p. 69-74
    In: Developmental Brain Research, Elsevier BV, Vol. 125, No. 1-2 ( 2000-12), p. 69-74
    Type of Medium: Online Resource
    ISSN: 0165-3806
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2000
    detail.hit.zdb_id: 1462706-1
    SSG: 12
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  • 3
    In: American Journal of Medical Genetics, Wiley, Vol. 101, No. 3 ( 2001-07-01), p. 286-287
    Type of Medium: Online Resource
    ISSN: 0148-7299 , 1096-8628
    URL: Issue
    RVK:
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    Language: English
    Publisher: Wiley
    Publication Date: 2001
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    detail.hit.zdb_id: 2143867-5
    detail.hit.zdb_id: 1493479-6
    detail.hit.zdb_id: 2205916-7
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    American Physiological Society ; 2011
    In:  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Vol. 300, No. 6 ( 2011-06), p. R1363-R1372
    In: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 300, No. 6 ( 2011-06), p. R1363-R1372
    Abstract: The liver has the unique capacity to regenerate after surgical resection. However, the regulation of liver regeneration is not completely understood. Recent reports indicate an essential role for small noncoding microRNAs (miRNAs) in the regulation of hepatic development, carcinogenesis, and early regeneration. We hypothesized that miRNAs are critically involved in all phases of liver regeneration after partial hepatectomy. We performed miRNA microarray analyses after 70% partial hepatectomy in rats under isoflurane anesthesia at different time points (0 h to 5 days) and after sham laparotomy. Putative targets of differentially expressed miRNAs were determined using a bioinformatic approach. Two-dimensional (2D)-PAGE proteomic analyses and protein identification were performed on specimens at 0 and 24 h after resection. The temporal dynamics of liver regeneration were characterized by 5-bromo- 2-deoxyuridine, proliferating cell nuclear antigen, IL-6, and hepatocyte growth factor. We demonstrate that miRNA expression patterns changed during liver regeneration and that these changes were most evident during the peak of DNA replication at 24 h after resection. Expression of 13 miRNAs was significantly reduced 12–48 h after resection ( 〉 25% change), out of which downreguation was confirmed in isolated hepatocytes for 6 miRNAs at 24 h, whereas three miRNAs were significantly upregulated. Proteomic analysis revealed 65 upregulated proteins; among them, 23 represent putative targets of the differentially expressed miRNAs. We provide a temporal miRNA expression and proteomic dataset of the regenerating rat liver, which indicates a primary function for miRNA during the peak of DNA replication. These data will assist further functional studies on the role of miRNAs during liver regeneration.
    Type of Medium: Online Resource
    ISSN: 0363-6119 , 1522-1490
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2011
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    SSG: 12
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  • 5
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 130, No. 3 ( 2012-09-01), p. e623-e630
    Abstract: Experimental studies suggest that platelet-triggered ductal sealing is critically involved in definite ductus arteriosus closure. Whether thrombocytopenia contributes to persistently patent ductus arteriosus (PDA) in humans is controversial. This was a retrospective study of 1350 very low birth weight (VLBW; & lt;1500 g) infants, including 592 extremely low birth weight (ELBW; & lt;1000 g) infants. METHODS: All infants who had a platelet count in the first 24 hours after birth and an echocardiogram performed on day of life 4 to 5 were included. The incidence of thrombocytopenia was analyzed in infants with and without PDA, and in those who did or did not undergo PDA intervention. The impact of thrombocytopenia, gestational age, birth weight, gender, and sepsis on PDA was determined by receiver operating characteristic curve, odds ratio, and regression analyses. RESULTS: Platelet numbers within the first 24 hours after birth did not differ between VLBW/ELBW infants with and without spontaneous ductal closure. Platelet numbers were not associated with subsequent PDA treatment. Low platelet counts were not related to failure of pharma-cologic PDA treatment and the need for subsequent surgical ligation. Lower gestational age or birth weight, male gender, and sepsis were linked to the presence of PDA in VLBW infants on day of life 4 to 5. CONCLUSIONS: Thrombocytopenia in the first 24 hours after birth was not associated with PDA in this largest VLBW/ELBW infant cohort studied to date. Impaired platelet function, due to immaturity and critical illness, rather than platelet number, might play a role in ductus arteriosus patency.
    Type of Medium: Online Resource
    ISSN: 0031-4005 , 1098-4275
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2012
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  • 6
    Online Resource
    Online Resource
    American Academy of Pediatrics (AAP) ; 2005
    In:  Pediatrics Vol. 116, No. 2 ( 2005-08-01), p. 521-522
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 116, No. 2 ( 2005-08-01), p. 521-522
    Type of Medium: Online Resource
    ISSN: 0031-4005 , 1098-4275
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2005
    detail.hit.zdb_id: 1477004-0
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  • 7
    Online Resource
    Online Resource
    American Academy of Pediatrics (AAP) ; 2008
    In:  Pediatrics Vol. 122, No. 2 ( 2008-08-01), p. 375-382
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 122, No. 2 ( 2008-08-01), p. 375-382
    Abstract: OBJECTIVE. Erythropoietin has been shown to be protective against hypoxic-ischemic and inflammatory injuries in cell culture, animal models of brain injury, and clinical trials of adult humans. The rationale for our study was that early administration of high-dose recombinant human erythropoietin may reduce perinatal brain injury (intraventricular hemorrhage and periventricular leukomalacia) in very preterm infants and improve neurodevelopmental outcome. We investigated whether administration of high-dose recombinant human erythropoietin to very preterm infants shortly after birth and subsequently during the first 2 days is safe in terms of short-term outcome. METHODS. This was a randomized, double-masked, single-center trial with a 2:1 allocation in favor of recombinant human erythropoietin. Preterm infants (gestational age: 24 to 31 weeks) were given recombinant human erythropoietin or NaCl 0.9% intravenously 3, 12 to 18, and 36 to 42 hours after birth. RESULTS. The percentage of infants who survived without brain injury or retinopathy was 53% in the recombinant human erythropoietin group and 60% in the placebo group. There were no relevant differences regarding short-term outcomes such as intraventricular hemorrhage, retinopathy, sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia. For 5 infants who were in the recombinant human erythropoietin group and had a gestational age of & lt;26 weeks, withdrawal of intensive care was decided (3 of 5 with severe bilateral intraventricular hemorrhage, 2 of 5 with pulmonary insufficiency); no infant of the control group died. Recombinant human erythropoietin treatment did not result in significant differences in blood pressure, cerebral oxygenation, hemoglobin, leukocyte, and platelet count. CONCLUSIONS. No significant adverse effects of early high-dose recombinant human erythropoietin treatment in very preterm infants were identified. These results enable us to embark on a large multicenter trial with the aim of determining whether early high-dose administration of recombinant human erythropoietin to very preterm infants improves neurodevelopmental outcome at 24 months' and 5 years' corrected age.
    Type of Medium: Online Resource
    ISSN: 0031-4005 , 1098-4275
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2008
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  • 8
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 3356-3356
    Abstract: Abstract 3356 Background: Thrombocytopenia affects 20–35% of patients admitted to Neonatal Intensive Care Units (NICUs). Platelet transfusions are usually administered to thrombocytopenic neonates at higher thresholds than those used for older children or adults, although there is a paucity of evidence to guide these decisions. Methods: In this study, we used a web-based survey to investigate the platelet transfusion thresholds used in level 1 NICUs (equivalent to level 3 in the US) in German-speaking European countries (Austria, Germany and Switzerland, AUT/GER/SUI). This survey was identical to the one previously used to investigate the transfusion practices of US neonatologists, thus allowing for a direct comparison of both populations. Eleven common clinical case scenarios of thrombocytopenia in preterm or term neonates were described and neonatologists were asked at which platelet count they would order a transfusion. For each case scenario, the median and the most frequently selected thresholds were determined. The Mann-Whitney-U-test was applied to compare the distribution of platelet transfusion thresholds between AUT/GER/SUI and US neonatologists. Univariate cumulative logit models (proportional odds model) were used to evaluate the differences between AUT/GER/SUI and US practices. In this analysis, an odds ratio 〉 1 indicates an increased odd to select a higher threshold. Results: At least one neonatologist from 100 of the 171 (58%) eligible level 1 NICUs (AUT n=2; GER n=92; SUI n=6) participated in the survey, for a total of 144 neonatologists. Their answers were compared with those of 1006 U.S. neonatologists previously surveyed. In 9 of the 11 scenarios, AUT/GER/SUI neonatologists selected substantially lower platelet transfusion thresholds than US neonatologists (P 〈 .0001). For example, in a preterm infant (27 weeks of gestation and 950g) who was clinically stable and not bleeding at two days of life, the median platelet transfusion threshold was 30×109/L in AUT/GER/SUI vs. 50×109/L in the US (P 〈 .0001). If the same infant had an intracranial hemorrhage, the most frequent threshold among AUT/GER/SUI neonatologists increased to 50×109/L, while most US neonatologists rose their trigger to 100×109/L (P 〈 .0001). To quantify the differences in transfusion practices between the two groups of physicians, we then calculated (for each case scenario) the odds of US neonatologists selecting a higher transfusion category than their European colleagues. In nine of the eleven scenarios the odds ratios were between 3.25 and 5.05, reflecting the high likelihood that a US neonatologist would choose a higher transfusion threshold than an AUT/GER/SUI neonatologist facing the same patient. Only in two case scenarios (term infant with alloimmune thrombocytopenia and premature infant prior to lumbar puncture) the odds ratios were 〈 2, reflecting more similar (although still significantly different) responses. Finally, in order to estimate the clinical impact of the observed differences, we recorded the platelet counts of every neonate admitted to our NICU over a six month period, and determined whether they would receive a platelet transfusion by extrapolating the answers of AUT/GER/SUI vs. US neonatologists to the first clinical vignette. Using this approach, we estimated that 18 out of 1000 neonates would be transfused if AUT/GER/SUI patterns were applied, compared to 33 transfused infants if US patterns were applied (1.8-fold increase). Conclusion: This first international comparative survey on platelet transfusion practices in neonates revealed substantially higher transfusion thresholds in the US than in AUT/GER/SUI. These differences might have substantial clinical implications, since platelet transfusions are associated with higher neonatal mortality and morbidity. In neonates with necrotizing enterocolitis and thrombocytopenia, receiving a higher number of platelet transfusions has been associated with a higher incidence of short bowel syndrome and cholestasis, and there is evidence to support the hypothesis that platelet transfusions can worsen bowel injury. Thus, well-designed clinical studies are needed to address the risks/benefits of these different approaches. Disclosures: Josephson: Immucor: Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 9
    Online Resource
    Online Resource
    American Society of Hematology ; 2006
    In:  Blood Vol. 107, No. 11 ( 2006-06-01), p. 4282-4290
    In: Blood, American Society of Hematology, Vol. 107, No. 11 ( 2006-06-01), p. 4282-4290
    Abstract: Molecular mechanisms for the developmental stage and tissue-specific regulation of the erythropoietin (EPO) gene are poorly understood. Recent findings indicate a role of the Wilms tumor suppressor, Wt1, in the formation of the hematopoietic system. Herein, we tested the hypothesis that Wt1 is a transcriptional regulator of the EPO gene. Binding of the transcriptionally competent Wt1(–KTS) isoform to the minimal EPO promoter was demonstrated by electrophoretic mobility shift assay and chromatin immunoprecipitation. Under normoxia, EPO expression was significantly increased in HEK 293 and HepG2 cells with forced expression of Wt1(–KTS). A reporter construct harboring the 117-bp minimal human EPO promoter was activated up to 20-fold by transient cotransfection of Wt1(–KTS) in different cell lines. Mutation of the Wt1 binding site in the EPO promoter abrogated this stimulatory effect of the Wt1(–KTS) protein. Hepatic Epo mRNA expression was significantly reduced in embryonic mice with homozygous Wt1 deletion. Furthermore, Wt1 and EPO were colocalized in hepatocytes of the liver and in neuronal cells of the dorsal root ganglia in developing mice. Both proteins were also detected in Sertoli cells of the adult murine testis. In conclusion, we identified Wt1(–KTS) as a novel transcriptional activator for the tissue-specific expression of the EPO gene.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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    detail.hit.zdb_id: 80069-7
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  • 10
    Online Resource
    Online Resource
    American Society for Microbiology ; 2011
    In:  Infection and Immunity Vol. 79, No. 2 ( 2011-02), p. 928-936
    In: Infection and Immunity, American Society for Microbiology, Vol. 79, No. 2 ( 2011-02), p. 928-936
    Abstract: Thrombopoietin (Tpo), which primarily regulates megakaryopoiesis, and its receptor (c-Mpl) are expressed in the brain, where Tpo exhibits proapototic effects on neurons. In the present study, we investigated the implication of Tpo in experimental pneumococcal meningitis. Following intrathecal infection with the encapsulated Streptococcus pneumoniae strain D39, we observed upregulation of Tpo mRNA expression at 12 h and 24 h in brain homogenates of wild-type C57BL/6 mice. c -Mpl mRNA expression was upregulated at 12 h and returned to baseline at 24 h. Compared to wild-type mice, mutants with homozygous Tpo receptor ablation (c -Mpl −/− ) displayed reduced microglial activation and neuronal apoptosis in the dentate gyrus. Concentrations of bacteria in blood or cerebrospinal fluid (CSF), as well as CSF pleocytosis, were not significantly different between wild-type and c- Mpl −/− mice. In human postmortem brain, Tpo protein was colocalized to macrophages during encephalitis. In murine primary microglia and RAW264.7 macrophages, upregulation of Tpo mRNA was induced by D39-conditioned medium but not by bacterial lipopeptide or by medium conditioned by pneumococcal mutants defective in hydrogen peroxide formation (Δ spxB ) or pneumolysin (Δ pln ). We conclude that Tpo acts as a mediator of neuronal damage in bacterial meningitis.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
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    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2011
    detail.hit.zdb_id: 1483247-1
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