Adult Astrogenesis and the Etiology of Cortical Neurodegeneration.

As more evidence points to a clear role for astrocytes in synaptic processing, synaptogenesis and cognition, continuing research on astrocytic function could lead to strategies for neurodegenerative disease prevention. Reactive astrogliosis results in astrocyte proliferation early in injury and disease states and is considered neuroprotective, indicating a role for astrocytes in disease etiology. This review describes the different types of human cortical astrocytes and the current evidence regarding adult cortical astrogenesis in injury and degenerative disease. A role for disrupted astrogenesis as a cause of cortical degeneration, with a focus on the tauopathies and synucleinopathies, will also be considered.

Association between degenerative spondylolisthesis and spinous process fracture after interspinous process spacer surgery.

BACKGROUND CONTEXT: Spinous process fracture is a recognized complication associated with interspinous process spacer (IPS) surgery. Although occasionally identified by plain radiographs, computed tomography (CT) appears to identify a higher rate of such fractures. Although osteoporotic insufficiency fracture is considered a contraindication for IPS surgery, a formal risk factor analysis for this complication has not previously been reported. PURPOSE: To identify risk factor(s) associated with early spinous process fracture after IPS surgery. STUDY DESIGN/SETTING: Prospective cohort study of 39 consecutive patients with lumbar stenosis and neurogenic claudication undergoing IPS surgery at a single institution. METHODS: Patients underwent preoperative dual-energy X-ray absorptiometry (DXA) scans, lumbar spine CT, and plain radiographs. Postoperatively, patients underwent repeat CT imaging within 6 months of surgery and serial radiographs at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year. Preoperative CT scans were analyzed by calculating average Hounsfield units for a 1 cm(2) area of the midsagittal reconstructed image for four separate locations: midvertebral body, subcortical bone subjacent to the superior margin of the midspinous process, subcortical bone above the inferior margin of the midspinous process, and the midspinous process. RESULTS: Thirty-eight patients underwent IPS surgery at a total of 50 levels (38 L4-L5, 12 L3-L4; 26 one-level, 12 two-level). One patient underwent laminectomy at index surgery and was excluded from the analysis. Implants included 34 titanium X-STOP (Medtronic, Memphis, TN, USA), 8 polyaryletheretherketone X-STOP (Medtronic, Memphis, TN, USA), and 8 Aspen (Lanx, Broomfield, CO, USA) devices. Eleven spinous process fractures were identified by CT in 11 patients (22.0% of levels). No fractures were apparent on plain radiographs. The rate of spondylolisthesis observed on preoperative radiographs was 100% (11 of 11) among patients with fractures compared with 33.3% (9 of 27) of patients without fracture (p=.0001). Overall, 21 of 39 patients in this series had spondylolisthesis, and the rate of fracture in this group was 52%. Among patients without spondylolisthesis, the fracture rate was 0%. A trend was observed toward decreased DXA lumbar spine and hip T-scores among fracture patients versus nonfracture patients (0.2 ± 1.7 vs. 0.8 ± 1.7; p=.389; -1.1 ± 1.4 vs. -0.3 ± 1.4; p=.201), but these differences were not significant. Similarly, bone density based on CT measurements at four different locations revealed a trend toward decreased density among fracture patients, but these differences were not significant. CONCLUSIONS: Degenerative spondylolisthesis appears strongly associated with the occurrence of spinous process fracture after IPS surgery. There is a trend toward increased fracture risk in patients with decreased bone mineral density as measured by both DXA scan and CT-based volume averaging of Hounsfield units, but osteoporosis appears to be a relatively weaker risk factor. The association between spondylolisthesis and fracture observed in this study may account for the relatively poorer outcome of IPS surgery in patients with spondylolisthesis that has been reported in previous series.

[Image guided dental implantology].

Dental implants insertion is a predictable surgical procedure with very high success rates. An optimal implants placement requires excellent surgical skills and good prosthetic perception. Performing an inaccurate implantation can lead to irreversible surgical damage on the one hand or a prosthetic failure on the other hand. Planning software provide the surgeon with good planning tool; existing navigation systems allow for translating them into performance by semi-active or passive guidance. The later allows for flexibility in the implant location during the operation and real-time tracking of drill position. All of these tools are helpful in avoiding damage to anatomical structures by performing the implantation in close relation to the CT scan. But the solutions that provide most possible advantages requires CT with special markers, long and expansive preoperative preparations and most of all a very high initial cost. These, in addition to a very long learning curve are the reason for these systems not to become a popular working tool. The most important challenges of the next generation systems in dental implants navigation are lower price, smaller size, good performance and reliability and ease of use. This kind of image guided system should allow for preplanning of implants locations, and guided insertion by minimal invasive procedure.

Transient expression of human interleukin-2 and interferon-gamma genes is regulated by interaction between distinct cell subsets.

The level of transient expression of human IL-2 and IFN-gamma genes, we show, is regulated by dynamic interaction between two functionally distinct cell populations. One is able to express these genes, while the other, bearing one of several specific surface markers, actively inhibits their expression. Defined cell subsets were isolated from PBMC and tonsil cells using immunomagnetic beads coated with monoclonal antibodies directed against surface markers. Depletion of CD8, CD11a (Leu15), or Leu8 subsets led to a pronounced superinduction of IL-2 and IFN-gamma gene expression when the remaining cell population was stimulated with mitogen (PHA) or antigen (SEB). Thus, a 10-fold increase in production of IFN-gamma was observed after removal of CD11a (Leu15) cells constituting only a small percentage of the total cell population. By contrast, depletion of cells expressing CD19, a B cell marker, did not yield any superinduction. Conversely, CD8, CD11a (Leu15), or Leu8 cell subsets, but not CD19 cells, each inhibited the induction of IL-2 and IFN-gamma gene expression almost completely in depleted or total cell populations from which they were derived. Gene expression occurring within one cell subset could be effectively inhibited by cells from a second subset. Introduction of inhibitory cells (Leu8) into a population that actively expressed IL-2 and IFN-gamma mRNA resulted in an immediate cessation of gene expression. This suppression involves a soluble mediator, since the culture medium in which such cells were activated exerted a similarly effective inhibition.

Regulation of human interleukin-2 and interferon-gamma gene expression by suppressor T lymphocytes.

Concomitant with induction of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) gene expression in human tonsil cells, mitogenic stimulation induces a transient activation of cells able to effectively suppress expression of these genes. Induction of IL-2 and IFN-gamma genes largely precedes appearance of suppressor cell activity, allowing expression of both genes to occur before strong down-regulation is exerted by activated suppressor cells. Suppressive activity induced in one cell population can inhibit IL-2 and IFN-gamma gene expression in another population from the same donor. The distinct nature of suppressor cells is supported by the absence of down-regulation of IL-2 gene expression in a helper cell line, MLA-144; yet, in these cells, negative control can be expressed when active suppressor cells are introduced. Our findings support the concept that actual levels of IL-2 and IFN-gamma gene activity are regulated to a large extent by the differential kinetics of activation of suppressor cells on one hand and of cells expressing the IL-2 and IFN-gamma genes on the other.

The potential to express or suppress human interleukin-2 and interferon-gamma genes is not restricted to distinct cell subsets.

Cell surface markers CD4, CD8, Leu8 and Leu15 (CD11) were used to separate human lymphoid cell subsets with monoclonal antibody-coated immunomagnetic beads. We show that each of these subsets is able to suppress the induction of IL-2 and IFN-gamma genes effectively. This is manifested by a pronounced superinduction of IL-2 and IFN-gamma mRNA, as well as IFN-gamma protein, in cell populations depleted of one of these subsets. Co-culture of cell subsets with total cell populations or depleted ones, on the other hand, leads to severe inhibition of expression of these genes. In these experiments, cells in suppressor subsets exhibit little, if any, expression of IL-2 and IFN-gamma genes. By contrast, depending on donor and lymphoid tissue examined (tonsils or peripheral blood mononuclear cells), CD4, CD8, Leu8, and Leu15 cell subsets are also able to express IL-2 or IFN-gamma genes to high levels. Moreover, in Leu8+ cells that do not express the IFN-gamma gene, extensive expression of both mRNA and protein can be elicited by inhibiting the activation of suppressor cells with gamma-irradiation before induction. These results support the concept that the potential to express or suppress human IL-2 and IFN-gamma genes is not restricted to distinct cell subsets. Suppression or expression can be elicited in cells carrying a given surface marker, depending on the state of the immune system in a lymphoid tissue.

Superinduction of the human gene encoding immune interferon.

Mitogen-induced interferon-gamma (IFN-gamma) gene expression was analyzed in human tonsil cells by titration of IFN-gamma activity and by quantitation of IFN-gamma mRNA. Expression of the IFN-gamma gene can be superinduced extensively by two distinct methods: exposure to various inhibitors of translation, or to low doses of gamma-irradiation. gamma-Irradiated cells produce, after exposure to cycloheximide, up to 12-fold greater amounts of IFN-gamma activity. Within as little as 4 h after the addition of translation inhibitors, IFN-gamma mRNA levels rise 3- to 5-fold. Superinduction acts to increase the size of the wave of IFN-gamma mRNA. Primary transcription of the IFN-gamma gene does not increase in cells superinduced by cycloheximide, nor can superinduction be explained by stabilization of IFN-gamma mRNA sequences. These findings show that, during normal induction, a labile protein acts post-transcriptionally to repress the accumulation of mature IFN-gamma mRNA sequences. The superinductive effects of cycloheximide and gamma-irradiation on levels of IFN-gamma are additive, suggesting that they affect different aspects of IFN-gamma gene expression. Superinduction by gamma-irradiation also has a post-transcriptional basis and is consistent with the possibility that expression of the IFN-gamma gene is normally controlled by the action of suppressor T cells. Even though the genes for human IFN-gamma and for interleukin-2 are both superinducible, a striking difference in the regulation of expression of these lymphokine genes is observed. Superinduction of IFN-gamma mRNA is not due to superinduction of interleukin-2.

Cancer-associated serum globulin demonstrated by polyacrylamide gel electrophoresis.

We evaluated the ability of polyacrylamide gel electrophoresis (PAGE) to measure protein band No. 1 (PB1) in serum as a means of discriminating between the sera of cancer patients and controls. Serum samples from 123 cancer patients, 155 subjects without clinically diagnosed cancer, and 6 members of families with a high incidence of cancer (total, 284) were obtained in Israel. An additional 214 serum samples from 80 cancer patients and 134 subjects without cancer were obtained from the Mayo Clinic-National Cancer Institute Serum Bank. Although a significantly higher proportion of serum specimens from cancer patients had positive results for PB1 by the PAGE method, the test at its current stage of development does not seem sufficiently discriminating for use in screening for cancer.