Notch/Delta4 interaction in human embryonic liver CD34+ CD38- cells: positive influence on BFU-E production and LTC-IC potential maintenance

We investigated whether Notch signaling pathways have a role in human developmental hematopoiesis. In situ histochemistry analysis revealed that Notch1, 2, and 4 and Notch ligand (Delta1-4, and Jagged1) proteins were not expressed in the yolk sac blood islands, the para-aortic splanchnopleure, the hematopoietic aortic clusters, and at the early stages of embryonic liver hematopoiesis. Notch1-2, and Delta4 were eventually detected in the embryonic liver, from 34 until 38 days postconception. Fluorescence-activated cell sorter analysis showed that first-trimester embryonic liver CD34(+)CD38(low) cells expressed both Notch1 and Notch2. When these cells were cultured on S17 stroma stably expressing Delta4, a 2.6-fold increase in BFU-E number was observed at day 7, as compared with cultures with control stroma, and this effect was maintained for 2 weeks. Importantly, exposure of these cells to Delta4 under these conditions maintained the original frequency and quality of long-term culture-initiating cells (LTC-ICs), while control cultures quickly resulted in the extinction of this LTC-IC potential. Furthermore, short-term exposure of embryonic liver adherent cells to erythropoietin resulted in a dose-dependent increase in Delta4 expression, almost doubling the expression observed with untreated stroma. This suggests that Delta4 has a role in the regulation of hematopoiesis after a hypoxic stress in the fetus.     

Fabry''s disease

Fifteen hemizygotes and 30 heterozygotes have been diagnosed since our investigations of Fabry's disease were started 10 years ago. They belong mainly to three Danish families. Genetic counseling and prenatal diagnoses have been performed, and in vitro studies of cultured fibroblasts and endothelial cells have been made with special reference to enzyme therapy.     

Association between condylar morphology and changes in bony microstructure and sub‐synovial inflammation in experimental temporomandibular joint arthritis

J Oral Pathol Med (2011) 40 : 111–120 Background: In juvenile idiopathic arthritis involvement of the temporomandibular joints (TMJs) is often associated with mandibular growth deviations. The relation between the growth deviations and severity of the inflammation, condylar shape, the micro‐architecture, and the quality of the bone has not previously been investigated. This paper studies the effect on the bony structures in mandibular condylar development in rabbits with antigen‐induced arthritis. Methods: Included were 42 juvenile rabbits with ovalbumin‐induced arthritis of the TMJs treated with intraarticular saline, intraarticular etanercept or subcutaneous etanercept. A TMJ from each animal was scanned using micro‐computed tomography and structural parameters were calculated. Three‐dimensional reconstructions of the mandibular condyle were scored blindly as normal or abnormal. TMJs were stratified for condylar morphology and were evaluated against data on trabecular structural parameters, inflammation, degree of mineralization, overall mandibular growth, and mineral apposition rate. Results: Abnormal morphology were seen in 15/32 animals available for data analysis. Erosions were an uncommon finding. Abnormal morphology was strongly related to the degree of inflammation. The trabecular separation was larger in group with abnormal morphology than in the group with normal morphology. Abnormal condylar morphology was not associated with overall mandibular growth. No differences were observed in mineral apposition rate. No differences in structural parameters were seen according to treatment modality. Conclusion: We showed that severe inflammation in the TMJs during mandibular development was associated with morphological changes in the mandibular condyle. These changes were predominantly seen at the macro‐morphological level and only very few differences were structural.     

Bioengineered AAV Capsids with Combined High Human Liver Transduction In Vivo and Unique Humoral Seroreactivity

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Long-Term Correction of Diabetes in Mice by In Vivo Reprogramming of Pancreatic Ducts

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Public attitudes and opinions toward physicians and dentists infected with bloodborne viruses: results of a national survey

BACKGROUND: There has been no recent assessment of public attitudes and opinions concerning risk of bloodborne virus transmission during health care. METHODS: Seven items in the 2000 annual Healthstyles survey were used to assess current attitudes and opinions about health care providers infected with human immunodeficiency virus (HIV) and the risk of bloodborne virus transmission during health care in a sample of approximately 3000 US households. RESULTS: Of the 2353 respondents, 89% agreed that they want to know whether their doctor or dentist is infected with HIV; 82% agreed that disclosure of HBV or HCV infection in a provider should be mandatory. However, 47% did not believe that HIV-infected doctors were more likely to infect patients than doctors infected with HBV or HCV. Opinions were divided on whether HIV-infected providers should be able to care for patients as long as they use good infection control: only 38% thought that infected providers should be allowed to provide patient care. CONCLUSIONS: These findings suggest that improved public education and risk communication on health care-associated bloodborne infections is needed.     

Combined effects of radiotherapy and angiostatin gene therapy in glioma tumor model

The objective of the present study was to evaluate the antitumor effect of a defective adenovirus expressing a secretable angiostatin-like molecule (AdK3) in combination with radiotherapy in rat C6 gliomas s.c. preestablished into athymic mice. In vitro, the combination regimen was significantly (P < 0.001) more cytotoxic for human microcapillary endothelial cells than either treatment alone, whereas survival of C6 glioma cells was not affected in the conditions used. Radiotherapy and AdK3 gene delivery was then studied on well established C6 xenografts (165 +/- 70 mm(3)). In these tumors, AdK3 intratumoral injections had only a marginal effect. Interestingly, when experimental radiotherapy was added, significantly higher (P < 0.005), and possibly synergistic, antitumoral effects were observed that tightly correlated a marked decrease of intratumoral vascularization. The combination of radiotherapy and AdK3 intratumoral injections also revealed a significant (P < 0.05) inhibition of tumor growth as compared with either treatment alone for larger tumors (467 +/- 120 mm(3)). Altogether, these data emphasize the potential of combining a destructive strategy directed against the tumor cells with an anti-angiogenic approach to fight cancer.