Autoreactive T lymphocytes are clonally deleted during maturation in the thymus. Deletion of T cells expressing particular receptor V beta elements is controlled by poorly defined autosomal dominant genes. A gene has now been identified by expression of transgenes in mice which causes deletion of V beta 14+ T cells. The gene lies in the open reading frame of the long terminal repeat of the mouse mammary tumour virus.
MxA is a GTPase that accumulates to high levels in the cytoplasm of interferon-treated human cells. Expression of MxA cDNA confers to transfected cell lines a high degree of resistance against several RNA viruses, including influenza, measles, vesicular stomatitis, and Thogoto viruses. We have now generated transgenic mice that express MxA cDNA in the brain and other organs under the control of a constitutive promoter. Embryonic fibroblasts derived from the transgenic mice were nonpermissive for Thogoto virus and showed reduced susceptibility for influenza A and vesicular stomatitis viruses. The transgenic animals survived challenges with high doses of Thogoto virus by the intracerebral or intraperitoneal route. Furthermore, the transgenic mice were more resistant than their nontransgenic littermates to intracerebral infections with influenza A and vesicular stomatitis viruses. These results demonstrate that MxA is a powerful antiviral agent in vivo, indicating that it may protect humans from the deleterious effects of infections with certain viral pathogens.
This study aimed to compare medial compartment contact pressures in knees treated with medial meniscal transplantation using either a bone plug or bone trough technique. Peak pressure, mean pressure, and contact area of the medial compartment were determined in 8 cadaveric specimens at 0° and 30° of flexion under a 1000-N load. Contact mechanics were measured for the intact knee, after meniscectomy, and after medial meniscal transplant with either a bone plug technique or a bone trough technique. Total medial meniscectomy resulted in decreased contact area, increased medial contact pressure, and increased medial peak contact pressure. When comparing meniscal transplant techniques at both 0° and 30°, no significant difference (P<0.05) was noted regarding contact mechanics after transplantation. The bone trough technique shows similar contact mechanics to the double bone plug technique and maintains the natural hoop stress of the meniscus during medial meniscal transplantation.[J Knee Surg. 2008;21:20-26.]
Autotransplantation of pancreatic microfragments into the liver or the spleen of totally pancreatectomized dogs is described. Both modes of transplantation resulted in restoration of normal fasting blood glucose levels. A delayed response to high glucose loads was however observed in both groups. Serum amylase levels indicated a rapid decline of exocrine activity. On the basis of postoperative levels of GOT and GPT in the serum of the dogs with intraportal transplants, permanent proteolytic or ischemic damage to the liver appeared unlikely.
Transgenic mice constitutively expressing in the brain the influenza virus resistance protein Mx1 controlled by the HMG (3-hydroxy-3-methylglutaryl coenzyme A reductase) promoter showed specific resistance against the neurotropic influenza A virus strain NWS. Control mice of the A2G strain express Mx1 protein in all organs, but only after induction by interferon type I upon or without viral infection. The extent of specific resistance in transgenic mice of the best-expressing line reached about two-thirds that of controls, most likely because of considerably less total-body Mx protein activity in the transgenic mice. Thus, the theoretical advantage in these mice of the continuous presence of Mx protein with early inhibitory potential to viral replication was apparently offset by restricted organ expression. Strong evidence that the Mx1 protein on its own is a specific anti-influenza A virus agent and that its efficiency in the experimental setting is independent of interferon actions could be derived from the treatment of experimental and control mice with anti-interferon antibodies at the time of virus tests. Whereas in A2G mice, Mx1 mRNA and Mx1 protein synthesis were abolished and viral resistance was markedly reduced or abolished, resistance in the transgenic mice persisted to almost the same degree. Transgenic mice generated with a mouse albumin/Mx1 cDNA construct showed liver-specific expression. However, in two expressing transgenic lines, Mx1 protein synthesis was suppressed after a few months. The mechanism of suppression could not be elucidated, but increasing methylation of the transgene's coding region was not the cause. It is possible that continuous Mx1 protein expression in the liver is less well tolerated than that in the brain. Whether this partial suppression and, with the HMG promoter, restricted organ expression are the organism's responses to interference of Mx1 with normal cellular activities such as nucleocytoplasmic transport of RNA and proteins cannot be determined until the molecular mechanisms of antiviral activity of Mx1 protein are understood.
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