Disease-specific hematopoietic cell transplantation: nonmyeloablative conditioning regimen for dyskeratosis congenita.

Dyskeratosis congenita (DC) is characterized by reticular skin pigmentation, oral leukoplakia and abnormal nails. Patients with DC have very short telomeres and approximately one-half have mutations in telomere biology genes. A majority of patients with DC develop BM failure (BMF). Hematopoietic cell transplantation (HCT) represents the only known cure for BMF in DC, but poses significant toxicities. We report six patients who underwent allogeneic HCT with a novel nonmyeloablative conditioning regimen specifically designed for DC patients. Graft sources included related PBSCs (1), unrelated BM (2) and unrelated double umbilical cord blood (3). Complete donor engraftment was achieved in five of six patients. One patient had initial autologous hematopoietic recovery, which was followed by a second transplant that resulted in 88% donor chimerism. With a median follow-up of 26.5 months, four patients are alive, three of whom were recipients of unrelated grafts. We conclude with this small study that encouraging short-term survival can be achieved with HCT in patients with DC using a preparative regimen designed to promote donor engraftment and minimize life-threatening disease-specific complications such as pulmonary fibrosis. Long-term follow-up will be crucial with respect to individualized patient care with each of the transplanted individuals.

Phytotoxicity of chlorinated aliphatics to hybrid poplar (Populus deltoides x nigra DN34).

Effects of a series of chlorinated ethenes and ethanes on hybrid poplar (Populus deltoides x nigra DN34) were assessed in laboratory experiments. Poplar cuttings were grown in sealed reactors with hydroponic solutions and were exposed to a chlorinated solvent for a period of two weeks. Exposure concentrations ranged from 0 to 0.4 mM for perchloroethylene to 0 to 8.4 mM for 1,1-dichloroethane. Effects were assessed by gravimetrically monitoring transpiration and measuring change in cutting mass. The zero-growth concentrations of the chemicals tested were 0.3 mM perchloroethylene, 0.9 mM trichloroethylene, 0.9 mM 1,1,2,2-tetrachloroethane, 2.0 mM 1,1,1-trichloroethane, 2.3 mM 1,1,2-trichloroethane, 4.8 mM trans-dichloroethylene, 5.6 mM 1,1-dichloroethylene, 6.0 mM cis-dichloroethylene, and 10.7 mM 1,1-dichloroethane. Adverse effects were found to increase with increasing number of chlorine atoms within a homologous series of ethenes or ethanes. Ethenes were more toxic than similarly chlorinated ethanes.

Advances in phytoremediation.

Phytoremediation is the use of plants to remedy contaminated soils, sediments, and/or groundwater. Sorption and uptake are governed by physicochemical properties of the compounds, and moderately hydrophobic chemicals (logarithm octanol--water coefficients = 1.0--3.5) are most likely to be bioavailable to rooted, vascular plants. Some hydrophilic compounds, such as methyl-tert-butylether and 1,4-dioxane, may also be taken up by plants via hydrogen bonding with transpiration water. Organic chemicals that pass through membranes and are translocated to stem and leaf tissues may be converted (e.g., oxidized by cytochrome P450s), conjugated by glutathione or amino acids, and compartmentalized in plant tissues as bound residue. The relationship between metabolism of organic xenobiotics and toxicity to plant tissues is not well understood. A series of chlorinated ethenes is more toxic to hybrid poplar trees (Populus deltoides x nigra, DN-34) than are the corresponding chlorinated ethanes. Toxicity correlates best with the number of chlorine atoms in each homologous series. Transgenic plants have been engineered to rapidly detoxify and transform such xenobiotic chemicals. These could be used in phytoremediation applications if issues of cost and public acceptability are overcome.