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.     

Serum esterase inhibition in birds: A nondestructive biomarker to assess organophosphorus and carbamate contamination

With the aim of proposing a nondestructive biomarker for monitoring the toxicological risk to birds of exposure to the organophosphorus insecticide azamethiphos and the carbamate insecticide methomyl, laboratory studies were performed on serum B esterases in Japanese quail (Coturnix coturnix japonica). The birds received two single dose treatments of each compound (azamethiphos and methomyl), i.e., 50 mg/kg and 250 mg/kg respectively. In the first treatment, serum butyrylcholinesterase (BChE) and carboxylesterase (CbE) were drastically inhibited in the azamethiphos-treated group, 24 h after the dose. No inhibition was detected for BChE and CbE activities in the methomyl-treated group, 24 h after the dose. In the second treatment, the birds died or were sacrified 3 h after the dose. Serum BChE and brain acetylcholinesterase (AChE) were strongly inhibited after treatment with both insecticides. Serum CbE, hepatic microsomal CbE and 7-ethoxyresorufin dealkylation activities were also inhibited. A statistically significant correlation between serum BChE and brain AChE was found at lethal and sublethal doses of these xenobiotics. The experimental results indicate that the nondestructive biomarker BChE can give an early qualitative and semi-quantitative warning of the toxic effects of organophosphate and carbamate insecticides in birds.     

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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