Allelic deletion analyses of MMAC/PTEN and DMBT1 loci in gliomas: relationship to prognostic significance

The frequency of loss of heterozygosity (LOH) around MMAC/PTEN and DMBT1 loci and survival analyses based on the LOH status were assessed in 110 patients with different histological groups of gliomas. Twenty-six of the patients had anaplastic oligodendrogliomas, 31 had anaplastic astrocytomas, and 53 had glioblastomas multiforme (GM). At the DMBT1 locus, LOH was observed very frequently in all three histological groups, with no significant difference in the frequency of LOH among the three histological groups. At the MMAC/PTEN locus, patients with GM exhibited a significantly increased frequency of LOH (72%) compared with patients with anaplastic astrocytomas (29%) or anaplastic oligodendrogliomas (31%) (P < 0.0001). Kaplan-Meier survival plots showed that patients with LOH at the MMAC/PTEN locus had a significantly worse prognosis than did patients without LOH at the MMAC/PTEN locus [hazard ratio (LOH versus non-LOH), 2.65; 95% confidence interval (CI), 1.69-4.46; P < 0.0001]. Cox proportional hazards regression analysis, adjusted for age at surgery and histological grades (GM and non-GM), showed that LOH at the MMAC/PTEN locus was a significant predictor of shorter survival [hazard ratio (LOH versus non-LOH), 2.01; 95% CI, 1.1-3.5; P = 0.018). Our analysis failed to indicate a similar association between the frequency of LOH at the DMBT1 locus and patient survival [hazard ratio (LOH versus non-LOH), 2; 95% CI, 0.37-3.13; P = 0.2]. These results suggest that the DMBT1 gene may be involved early in the oncogenesis of gliomas, whereas alterations in the MMAC/PTEN gene may be a late event in the oncogenesis related to progression of gliomas and provide a significant prognostic marker for patient survival.     

Overexpression of cardiotrophin-1 and gp130 during experimental acute Chagasic cardiomyopathy

The purpose of this study was to examine how antigen retrieval affected the yield of immunogold labeling on epoxy sections based on embedding with different amounts of accelerator. The concentration of accelerator DMP-30 (tri(dimethyl amino methyl) phenol) was varied in the range of 0-8% in the processing of the tissue for epoxy embedding. Immunogold labeling was performed on epoxy sections and LR-White sections of fibrin clots and renal tissue with IgG-deposits, and the antibodies used were anti-fibrinogen anti-IgG and, respectively. For some of the sections antigen retrieval was performed by heating the sections in citrate buffer. In all cases, the yield of immunogold labeling increased following antigen retrieval. The increase (%) in the yield of immunogold labeling as a result of antigen retrieval was larger for epoxy sections than for LR-White sections. The immunolabeling on high-accelerator epoxy sections exposed to antigen retrieval was about 20% more intense than on untreated LR-White sections both for IgG and fibrinogen. In addition to breaking fixations bonds introduced by the chemical fixation, we believe that the antigen retrieval also breaks bonds between the epoxy resin and the embedded tissue. The combination of increased amount of accelerator during tissue processing for epoxy embedding and antigen retrieval by heating in citrate buffer is a potent method for increasing specific immunolabeling on epoxy sections.     

UVB radiation interrupts cytokine-mediated support of an epidermal-derived dendritic cell line (XS52) by a dual mechanism

We have established long-term dendritic cell lines from the epidermis of newborn mice. These cell lines (XS series) proliferate maximally in response to granulocyte/macrophage-colony stimulating factor, as well as to CSF-1, which is produced by skin-derived NS fibroblast lines and by keratinocytes (albeit in smaller amounts). The purpose of this study was to examine the impact of UVB radiation on CSF-1-mediated interaction of dendritic cells with fibroblasts and keratinocytes. Exposure of NS cells to UVB radiation (unfiltered FS20 sunlamp) decreased CSF-1 production at mRNA and protein levels. Both changes occurred in a dose-dependent fashion, with 50 J/m2 causing a significant reduction. UVB radiation also downregulated CSF-1 mRNA expression by Pam 212 keratinocytes. UVB exposure of XS cells diminished the surface expression of CSF-1 receptors, with 50 J/m2 causing a significant reduction. Thus, UVB radiation interrupts CSF-1-mediated cell-cell interaction by a dual mechanism: downregulating CSF-1 production and abrogating CSF-1 receptor expression. Importantly, granulocyte/macrophage-colony stimulating factor receptor expression by XS cells was also inhibited by UVB radiation, once again, with 50 J/m2 producing significant inhibition. We propose that the resulting CSF-1 deficiency in epidermal microenvironment and unresponsiveness by dendritic cells to relevant growth factors may contribute to UVB-mediated loss of resident epidermal dendritic cells (i.e., Langerhans cells) in skin.     

Characterization of t(11;14) translocation in mantle cell lymphoma by fluorescent in situ hybridization

Characterization of chromosome abnormalities in leukemia and lymphoma have contributed to the understanding of the molecular basis of these neoplastic diseases. In addition, specific chromosomal aberrations have acquired diagnostic or prognostic value. The t(11;14)(q13;q32) chromosome translocation has been detected in mantle cell lymphomas. However, possibly due to the limits of conventional cytogenetic analysis and the presence of different breakpoints at the molecular level, it is possible that the true percentage of association is underestimated. In our study, we used a yeast artificial chromosome, spanning the entire area where the rearrangements occur on chromosome 11q13, to detect the presence of translocations by fluorescent in situ hybridization experiments. We detected BCL-1 translocations in eight of eight patients with clinical and immunological features of mantle cell lymphoma, suggesting that the t(11;14) translocation is a critical event in the pathogenesis of MCL and may be a primary element for the diagnosis. Since this translocation is associated with poor prognosis, its detection may help to make a correct diagnosis as well as to evaluate residual disease, which is critical to plan a rational chemotherapy regimen.     

Lumbosacral movement in the sit-and-reach and in Cailliet's protective-hamstring stretch

STUDY DESIGN: This study analyzed movement characteristics of subjects as they performed two different hamstring stretching activities. OBJECTIVES: The study determined if there were differences in lumbosacral movement as the subjects performed the two stretches. SUMMARY OF BACKGROUND DATA: Cailliet contends that his protective hamstring stretch is less apt to be stressful to the structures of the spine than is a more commonly done sit-and-reach stretching activity. No previous biomechanical investigation has tested his contention. METHODS: Lumbosacral movement was measured with an Ady-Hall lumbar monitor as 40 university students (20 males, 20 females) performed a popular sit-and-reach test and a sit-and-reach test that subscribed to Cailliet's protective hamstring stretch protocol. RESULTS: Lumbosacral movement was almost identical in the two stretching activities. CONCLUSIONS: If lumbosacral movement is the only criterion to consider in evaluating the safety of these two stretching activities, it makes little difference which activity is chosen. If moment of inertia were the dependent variable rather than lumbosacral movement, possibly one activity may be less stressful to the structures of the spine than the other.     

Survival of cylindrical implants in composite grafted maxillary sinuses

PURPOSE: This retrospective study investigated the survival of dental implants placed in the maxilla after composite grafting of the sinus and an average of 55 months of loading. PATIENTS AND METHODS: Maxillary sinuses of 88 patients were grafted with autogenous cancellous bone combined with dense hydroxyapatite particles. After an average healing period of 3.4 months, hydroxyapatite-coated titanium endosseous implants were placed. A total of 388 implants were placed in grafted sinus floors, and 82 were placed in onlay grafted nonsinus position in the canine region. The implants were loaded with overdentures and fixed bridges 4 months (mean) after implantation, with a follow-up for a mean of 55 months. RESULTS: The cumulative implant survival was calculated according to the Kaplan-Meier method. Implant survival from the time of loading was 89% in full reconstructed cases and 90% in partially edentulous cases. The overall cumulative implant survival rate, including the loss in the surgical stage, was 82%. CONCLUSION: Implant loss in composite grafted maxillae after 70 months of follow-up was similar to loss in nongrafted maxillae.