Differentiation state and responses to hematopoietic growth factors of murine myeloid cells transformed by myb

Murine hematopoietic cells can be transformed in vitro by recombinant retroviruses that express the myb oncogene, and hematopoietic growth factor (HGF)-dependent myeloid cell lines can be derived from these transformed primary cells. In this study, the differentiation state and responses of myb-transformed hematopoietic cells (MTHCs) have been investigated. We find that MTHCs exhibit properties of early myeloid progenitors including synergistic responses to combinations of HGFs and expression of certain surface markers. As reported previously, MTHCs respond well to granulocyte-macrophage colony-stimulating factor (GM- CSF) but can also respond to interleukin-3 (IL-3); the response to the latter factor depends on the mouse strain from which the cells are derived. Although these single factors stimulate MTHCs, combinations of these factors with colony-stimulating factor-1 (CSF-1 or M-CSF) or Steel factor (SLF or SCF) act synergistically to promote colony formation. The surface markers expressed by MTHCs include both granulocyte-macrophage lineage specific antigens Gr-1, 7/4, F4/80, and Mac-1, as well as two antigens found on early progenitors and stem cells--Thy-1 and Sca-1 (Ly6E). Expression of the latter markers is often heterogeneous and can be modulated by the growth factors to which the cells are exposed. Finally, we show that monocytic differentiation of MTHCs can be induced by exposure to tumor necrosis factor (TNF alpha). Taken together, these results suggest that MTHCs will be a useful model for studying HGF/cytokine responses in both proliferation and differentiation.     

Dysglycemias in pregnancy: from diagnosis to treatment. Brazilian consensus statement

There is an urgent need to find consensus on screening, diagnosing and treating all degrees of DYSGLYCEMIA that may occur during pregnancies in Brazil, considering that many cases of DYSGLYCEMIA in pregnant women are currently not diagnosed, leading to maternal and fetal complications. For this reason the Brazilian Diabetes Society (SBD) and the Brazilian Federation of Gynecology and Obstetrics Societies (FEBRASGO), got together to introduce this proposal. We present here a joint consensus regarding the standardization of clinical management for pregnant women with any degree of Dysglycemia, on the basis of current information, to improve medical assistance and to avoid related complications of Dysglycemia in pregnancy to the mother and the fetus. This consensus aims to standardize the diagnosis among general practitioners, endocrinologists and obstetricians allowing the dissemination of information in basic health units, public and private services, that are responsible for screening, diagnosing and treating disglycemic pregnant patients.     

Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs

Background  

Exosomes or secreted bi-lipid vesicles from human ESC-derived mesenchymal stem cells (hESC-MSCs) have been shown to reduce myocardial ischemia/reperfusion injury in animal models. However, as hESC-MSCs are not infinitely expansible, large scale production of these exosomes would require replenishment of hESC-MSC through derivation from hESCs and incur recurring costs for testing and validation of each new batch. Our aim was therefore to investigate if MYC immortalization of hESC-MSC would circumvent this constraint without compromising the production of therapeutically efficacious exosomes.     

Assessment of patented coronary end-to-side anastomotic devices using micromechanical bonding

BACKGROUND: Despite multiple patented ideas for vascular end-to-side anastomotic devices, and the growing need for them in minimally invasive coronary bypass procedures, no device has been evaluated clinically yet. This study assessed patents of micromechanical end-to-side anastomotic devices with respect to application in coronary artery bypass grafting. METHODS: Patents were categorized with respect to their micromechanical bonding principle. Calculated values for the wall strain during the construction of an anastomosis were compared with the allowable strain for human coronary arteries. RESULTS: From 51 patents describing vascular anastomotic devices, 11 ideas, categorized into four groups (staples, clips, mounting systems, and intraluminal stent structures), are serious candidates for coronary end-to-side anastomoses. Most ideas use an anvil for proper application of the bonding elements. For small (1.5 mm) coronary arteries, the calculated wall strain was 0.87, exceeding the breaking strain (0.45) in 60- to 79-year-old patients. CONCLUSIONS: In a coronary anastomotic device, the concept of using an anvil for the application of micromechanical bonding elements is not attractive, because excessive wall strain is likely to occur.     

Changes in peripheral blood CD5 (Bla) B-cell populations and autoantibodies following blood transfusion

BACKGROUND: CD5 B cells and the natural autoantibodies they produce play a role in antigen presentation, tolerance induction, and maintenance of an idiotypic immune network. The effects of transfusion on autoantibodies and peripheral blood CD5 B cells were studied. STUDY DESIGN AND METHODS: Eight previously transfused patients with sickle cell anemia and five patients who underwent orthopedic surgical procedures with transfusion were enrolled in the study. Patients in both groups received 1 to 2 units of allogeneic packed red cells. Ten untransfused healthy adults and five patients who underwent orthopedic surgery without transfusion were enrolled as controls. Peripheral blood CD5 B cells, serum levels of IgM, antinuclear antibodies, rheumatoid factor, and anticardiolipin IgM were quantitated either at the beginning of the study (baseline sample), before transfusion, or before surgery and either at 1-, 2-, 4-, 6-, and 8-week intervals after transfusion, after surgery, or after the baseline sample was obtained. RESULTS: IgM levels and the absolute number of B cells that coexpressed CD5 rose to twice pretransfusion levels in six of eight transfused sickle cell anemia patients and in four of five transfused orthopedic surgery patients. No comparable increases in CD5 B cells were noted in untransfused controls. Preexisting rheumatoid factor and antinuclear antibody levels increased in four of five transfused orthopedic surgery patients. One sickle cell anemia patient developed anti-Fya despite receiving Fya-negative blood. Increasing titers of anti-Fya paralleled the increases in IgM and CD5 B cells after transfusion. One patient who developed a positive direct antiglobulin test after transfusion had large increases in serum anticardiolipin IgM. Anticardiolipin IgM was subsequently eluted from direct antiglobulin test-positive red cells obtained after transfusion. Antibodies with anti-Fya-like activity and anticardiolipin IgM were produced in vitro by CD5 B cells and not by conventional CD5-negative B cells. CONCLUSION: An association was found between transfusion-induced increases in CD5 B cells and increased autoantibody production. These data may have implications for immunologic intervention to prevent the induction of red cell antibodies and other changes in the immune system caused by exposure to foreign antigens via blood transfusion.     

Interim and temporary restoration of teeth during endodontic treatment

One of the main aims of endodontic treatment is to eliminate micro-organisms from within the root canal system. A further aim is to prevent the ingress of any further bacteria during and after treatment. These aims are usually achieved by various means and stages throughout the treatment process. Endodontic treatment is usually performed on teeth that have lost the integrity of the external coronal tooth structure which has allowed bacteria to enter the tooth and ultimately reach the pulp space. Further opening of the tooth occurs when an endodontic access cavity is made to allow treatment to be performed. Hence, there will always be a need for interim and temporary restoration of teeth undergoing endodontic treatment. Many different materials and techniques have been proposed, and these proposals have been based on many research reports. The purposes of this article are to review the literature regarding the use of interim and temporary restorations, and to provide recommendations regarding such restorations for clinicians to follow when providing endodontic treatment.     

Permanent wall stretching in porcine coronary and internal mammary arteries

BACKGROUND: Anastomotic connectors may induce substantial arterial wall deformation and, hence, wall injury. We studied arterial wall damage and repair after sustained large longitudinal elongation in the porcine coronary and internal mammary arteries in vivo. METHODS: A stretch device that elongates a part of the artery by 80% was implanted in 8 pigs. Elongated coronary arteries (n = 14) and internal mammary arteries (n = 15) were examined histologically at either 2 days (4 pigs) or 5 weeks of follow-up (4 pigs). RESULTS: No mural thrombus was observed at the elongated site. In the coronary artery at 2 days, few and only minor histologic changes were found. At 5 weeks, in two of seven coronary segments, a thin rim of intimal hyperplasia was found, in one case with a maximum thickness of 76 micro m. The internal mammary artery hardly showed any changes. CONCLUSIONS: Permanent longitudinal elongation by 80% caused little structural changes in the porcine coronary and internal mammary artery wall. Anastomotic connectors that impose relatively large deformations can be safely evaluated in the pig.