Gene therapy for the induction of chimerism and transplant tolerance

Technical advances in transplant surgery and the development of powerful and effective immunosuppressive drugs have contributed to the success of organ transplantation as a medical treatment for patients with end-stage diseases. Associated with this procedure, however, is a dependence on life-long immunosuppressive drugs, which are required to prevent graft rejection. These agents render the patient susceptible to infections, tumors and various side affects. The ability to achieve tolerance to organ grafts would free transplant patients from lifelong dependency on pharmacological agents with harmful side effects. Several laboratories have shown that tolerance can be achieved by the induction of mixed cell chimerism and/or by molecular chimerism achieved by gene transfer techniques prior to graft placement. Molecular chimerism, induced by transplantation of autologous bone marrow expressing either allo- or xenoantigens has the potential to induce tolerance without the development of graft vs. host disease. The application of gene transfer techniques to induce chimerism has been shown to reshape the immune repertoire by mechanisms that include clonal deletion, the induction of central tolerance or generation of regulatory T cells that would eliminate the need for immunosuppressive drugs. Optimization of this methodology for clinical use could therefore revolutionize the field of transplantation. This review summarizes the recent studies which have compared the efficacy of different vectors, conditioning regimens, and transduction conditions leading to new and improved techniques for the application of gene therapy to induce chimerism and transplant tolerance to both allografts and xenografts.     

Facial profile changes in early Class II correction with cervical headgear

OBJECTIVE: To characterize the effects of early cervical headgear treatment on the facial profile of children in Class II division 1 malocclusion. MATERIALS AND METHODS: Forty children aged 9.1 (7.2-11.5) years with Class II division 1 malocclusion were treated using a cervical headgear appliance. The headgear consisted of a long outer bow bent upward 15 degrees and a large expanded inner bow. Lateral cephalograms were taken before and after treatment, and the facial profile was estimated from the cephalograms. The results were compared to an age- and sex-matched normal cohort of 644 Finnish children. RESULTS: Class I molar relationship was achieved in all treated children. The treatment time was 1.6 (0.3-3.1) years on average. Compared to the controls, the treatment restricted the forward growth of maxillary A-point, and the SNA angle decreased 1.4 degrees +/- 1.2 degrees per year (P < .00001). Decreased maxillary prognathism was associated with decreased facial convexity, g-sn-pg (P = .02), and the ANB (P < .00001) angles decreased compared to the controls. Upper lip protrusion (distance ls to sn-pg; P < .00001) was decreased, and the nasolabial angle (cm-sn-ls) widened despite the increased facial inclination of the upper incisors (P = .0005). The treatment significantly decreased the gap between the lips (P = .0009) in their relaxed position. CONCLUSION: Cervical headgear treatment in Class II correction is associated with a decreased facial convexity caused by the restriction of forward growth of the maxillary A-point, while the rest of the facial profile, including the mandible, continue to grow forward at a normal rate.     

Ophiobolin A from Bipolaris oryzae Perturbs Motility and Membrane Integrities of Porcine Sperm and Induces Cell Death on Mammalian Somatic Cell Lines

Bipolaris oryzae is a phytopathogenic fungus causing a brown spot disease in rice, and produces substance that strongly perturbs motility and membrane integrities of boar spermatozoa. The substance was isolated from the liquid culture of the fungal strain using extraction and a multi-step semi-preparative HPLC procedures. Based on the results of mass spectrometric and 2D NMR techniques, the bioactive molecule was identified as ophiobolin A, a previously described sesterterpene-type compound. The purified ophiobolin A exhibited strong motility inhibition and viability reduction on boar spermatozoa. Furthermore, it damaged the sperm mitochondria significantly at sublethal concentration by the dissipation of transmembrane potential in the mitochondrial inner membrane, while the plasma membrane permeability barrier remained intact. The study demonstrated that the cytotoxicity of ophiobolin A toward somatic cell lines is higher by 1–2 orders of magnitude compared to other mitochondriotoxic mycotoxins, and towards sperm cells unique by replacing the progressive motility by shivering tail beating at low exposure concentration.     

Identification of Deep Sleep and Awake with Computational EEG Measures

The objective of the present work was to examine identification of deep sleep and awake with computational analysis of sleep EEG traces from central brain regions. All-night EEG traces from a total of 56 male subjects, 22 healthy control subjects and 34 age-matched apnea patients, were examined. A spectral mean frequency measure, a Hilbert transform based EEG amplitude and a correlation coefficient method were compared. The EEG amplitude provided a good identification of deep sleep, reaching 86.25% but was relatively poor in the identification of wakefulness, reaching 39.06%. Mean frequency provided a relatively good identification of deep sleep and awake, reaching 84.66% and 77.67%, respectively, while the correlation coefficient produced the lowest results of 37.89% and 44.43%. Optimal threshold values for deep sleep and awake identification were determined as 4.20 and 9.76 Hz, respectively, for the mean frequency measure. Mean frequency measure can be used to provide overall context information about sleep depth for automated sleep EEG analysis methods.     

Predictors and reasons for epilepsy patients to decline surgery: a prospective study

Journal of Neurology - In patients with drug-resistant focal epilepsy, resective surgery is the most successful treatment option to achieve seizure freedom. However, a surprisingly high rate of...     

Mannose-receptor positive and negative mouse macrophages differ in their susceptibility to infection by Chlamydia species.

It has been shown that N-linked high mannose type oligosaccharides competitively inhibits attachment to and infectivity of chlamydiae in HeLa cells. To further study whether mannose moieties are involved in the infectivity of chlamydiae, the susceptibility of mannose-receptor negative J774A and positive J774E mouse macrophages to Chlamydia trachomatis, Chlamydia psittaci and Chlamydia pneumoniae was evaluated. C. trachomatis infected mannose-receptor positive cells better than mannose-receptor negative cells. C. psittaci infected both mannose-receptor negative and positive cells equally well, while C. pneumoniae infected mannose-receptor negative cells better than mannose-receptor positive cells. Further studies using this system may provide insight into the role of mannose-receptor in attachment, entry and survival of chlamydiae in macrophages.