Array-based diagnostic gene-expression score for atopy and asthma

Whether gene expression is useful in discriminating different atopic phenotypes is unclear. The aim of the study was to evaluate a gene-expression score for the diagnosis of atopy and asthma and to assess disease activity as a guide for therapeutic decisions. Purified mRNA from PBMCs of 18 atopic asthmatic subjects, 8 atopic nonasthmatic subjects, and 14 healthy control subjects was hybridized to cDNA membranes. A composite atopy gene expression (CAGE) score was determined by using 10 genes dysregulated in atopic individuals according to a specific algorithm. The CAGE score was better than total IgE in differentiating atopic from nonatopic subjects (sensitivity, 96%; specificity, 92%). Correlation between the CAGE score and total IgE (P <.001) was found, and there was a trend for correlation with asthma severity (P =.051). The CAGE score was able to quantify phenotype-specific alteration in gene expression of atopic individuals. The CAGE score might be used as a diagnostic tool or to monitor the effects and side effects of therapy.     

TCP is hardly resorbed and not osteoconductive in a non-loading calvarial model

Tricalciumphosphate (TCP) has been used as a ceramic bone substitute material in the orthopedic field as well as in craniofacial surgery. Some controversies exist concerning the osteoconductive potential of this material in different implantation sites. This study was designed to evaluate the biological response of calvarial bone towards TCP granules under non-loading conditions to assess the potential of TCP as a biodegredable and osteoconductive bone substitue material for the cranial vault. Full-thickness non-critical size defects were made bilaterally in the calvaria of 21 adult Wistar rats. One side was filled by TCP granules, the contralateral side was left empty and used as a control. Animals were sacrified in defined time intervals up to 6 months. Bone regeneration was analyzed with special respect toward the micromorphological and microanalytical features of the material-bone interaction by electron microscopy and electron diffraction analysis. Histologic examination revealed no TCP degradation even after 6 months of implantation. In contrast, a nearly complete bone regeneration of control defects was found after 6 months. At all times TCP was surrounded by a thin fibrous layer without presence of osteoblasts and features of regular mineralization. As far as degradation and substitution are concerned, TCP is a less favourable material tinder conditions of non-loading.     

Mapping chromosomal breakpoints of Burkitt's t(8;14) translocations far upstream of c-myc.

To analyze the region upstream of c-myc, a number of novel probes were established. These were generated by chromosomal walking starting from the breakpoint of the chromosomal translocation of the B-cell line 380 and by cloning the breakpoint of the translocation of the Burkitt lymphoma cell line IARC/BL72. Using the newly isolated probes a detailed physical map of 500 kilobases of the region upstream of c-myc was established applying pulsed-field gel electrophoresis. The chromosomal breakpoint of IARC/BL72 cells was mapped to a site 55 kilobases 5' of c-myc. A region 20 kilobases in length and containing the breakpoints of 380, EW36, P3HR-1, and Daudi cells was identified 170-190 kilobases upstream of c-myc. In addition the HPV18 integration site in HeLa cells was located between 340 and 500 kilobases 5' of c-myc. The probes were used to define the c-myc amplification units in Colo320-HSR and HL60 cells as well as in four cases of small cell lung cancer. Evidence is provided that the amplicon of HL60 cells is discontinuously organized.     

Impact of blood transfusion and burn injury on microbial translocation and bacterial survival

The role of the immune system in microbial translocation must be clarified. In these studies, the effect of blood transfusion-related immunosuppression on translocation was investigated in a burn animal model previously known to increase the gut's permeability to 14C-radiolabeled Escherichia coli. In a first experiment, Balb/c mice underwent transfusion (T) with 0.2 mL per mouse of allogeneic C3H/HeJ mouse blood 5 days prior to undergoing 30-percent burn injury (B) and simultaneous gavage (G) with 10(9) E. coli bacteria labeled with 14C. An additional six groups of Balb/c mice underwent different combinations of T, B, and G procedures (TG, BG, TB, T, B, G). Survival rate was recorded for all groups on Day 10. This experiment suggested that B and T, to a lesser extent, were the factors affecting survival, although the combination of T, B, and G clearly showed a synergistic effect on mortality. In a second experiment, 18 Balb/c mice belonging to TBG, BG, TG, and G groups were sacrificed 1, 4, and 24 hours after burn or gavage. The residual radioactivity and the percentage of viable bacteria were computed for mesenteric lymph nodes, spleen, liver, lungs, blood, and peritoneal fluid. Statistical analysis of the radionuclide counts recognized B as the only variable able to enhance the magnitude of 14C E. coli translocation. The percentage of viable bacteria showed that T and, more moderately, B were the factors leading to the failure of bacterial clearance in the tissues.     

Optimal control of the penicillin G fed-batch fermentation: An analysis of the model of heijnen et al.

This paper presents the application of optimal control theory in determining the optimal feed rate profile for the penicillin G fed-batch fermentation, using a mathematical model based on balancing methods. Since this model does not fulfil all requisites for standard optimal control, we propose a sequence of new models — that converges to the original one in a smooth way — to which the standard techniques are applicable. The unusual optimization of some initial conditions is included. We then state the conjecture that allows us to obtain the optimal control for the original model. The enormous gains in production and the vanishing of the characteristic biphasic behaviour through feed rate profile optimization raise some questions concerning the validity of this model. In this way this optimal control study can prove to be very useful for model discrimination purposes. Furthermore, mathematical and microbial insights lead to the construction of a suboptimal heuristic strategy — which we show to be a limiting case of the optimal scheme — that can serve as a basis for the development of robust, model-independent, optimal adaptive control schemes.     

Incision design in implant dentistry based on vascularization of the mucosa

OBJECTIVES: The delivery of an adequate amount of blood to the tissue capillaries for normal functioning of the organ is the primary purpose of the vascular system. Preserving the viability of the soft tissue segment depends on the soft tissue incision being properly designed in order to prevent impairment of the circulation. A knowledge of the course of the vessels as well as of their supply area are crucial to the decision of the incision. The aim of this study was to visualize the course of the arteries using different techniques, to perform macroscopic- and microscopic analyses, and to develop recommendations for incisions in implant dentistry. MATERIAL AND METHODS: The vascular systems of seven edentulous human cadavers were flushed out and filled with either red-colored rubber bond or Indian ink and formalin mixture. After fixation a macroscopic preparation was performed to reveal the course, distribution and supply area of the major vessels. In the area of the edentulous alveolar ridge specimens of the mucosa were taken and analyzed microscopically. RESULTS: The analyses revealed the major features of mucosal vascularization. The main course of the supplying arteries is from posterior to anterior, main vessels run parallel to the alveolar ridge in the vestibulum and the crestal area of the edentulous alveolar ridge is covered by a avascular zone with no anastomoses crossing the alveolar ridge. CONCLUSION: The results suggest midline incisions on the alveolar ridge, marginal incisions in dentated areas, releasing incisions only at the anterior border of the entire incision line, and avoidance of incisions crossing the alveolar ridge.     

Biological and biophysical principles in extracorporal bone tissue engineering. Part II

The aim of this review is to characterise the biological and biophysical background of in vitro bone tissue engineering. The paper focuses on basic principles in extracorporal engineering of bone-like tissues, considering parameters such as scaffold design, tissue construction, bioreactors, and cell stimulation in vivo and in vitro. Scaffolds have a key function concerning cellular invasion and bone formation. The intra-architectural scaffold geometry, as well as the scaffold material, play an important role in the process of bone regeneration. Various types of bioreactors have been tested for their utility in bone substitute fabrication that is clinically effective and reproducible. Sophisticated bioreactor systems are those that mimic the three-dimensional morphology and the mechanical situation of bones. Mechanical stimulation as well as other biophysical stimuli appear to be critical factors for proliferation and differentiation of bone cells and for bone mineral and structure formation. Furthermore an enhancement of bone regeneration by application of chemical stimulation factors is discussed.