Duplication of the PMP22 gene in 17p partial trisomy patients with Charcot-Marie-Tooth type-1A neuropathy

Autosomal dominant Charcot-Marie-Tooth type-1A neuropathy (CMT1A) is a demyelinating peripheral nerve disorder that is commonly associated with a submicroscopic tandem DNA duplication of a 1.5-Mb region of 17p11.2p12 that contains the peripheral myelin gene PMP22. Clinical features of CMT1A include progressive distal muscle atrophy and weakness, foot and hand deformities, gait abnormalities, absent reflexes, and the completely penetrant electrophysiologic phenotype of symmetric reductions in motor nerve conduction velocities (NCVs). Molecular and fluorescence in situ hybridization (FISH) analyses were performed to determine the duplication status of the PMP22 gene in four patients with rare cytogenetic duplications of 17p. Neuropathologic features of CMT1A were seen in two of these four patients, in addition to the complex phenotype associated with 17p partial trisomy. Our findings show that the CMT1A phenotype of reduced NCV is specifically associated with PMP22 gene duplication, thus providing further support for the PMP22 gene dosage mechanism for CMT1A. Received: 3 May 1995 / Revised: 1 August 1995     

Tumor Suppressor Gene-Derived Peptide Antigens

Foreign and self endogenous proteins can be processed and presented as peptides bound to class I and II MHC to CD8 or CD4-positive T cells. In the case of mutant tumor suppressor proteins, proteosomal processing of the mutant protein could occur either in the tumor cell or in an antigen-presenting cell to generate a variety of peptides that can be transported into the endoplasmic reticulum and loaded on the MHC. These peptides may induce tumor suppressor specific T cells in the presence of sufficient T help and costimulation. In human cancer, p53 is frequently found to be both somatically mutant and overexpressed. We and others are currently investigating the potential of peptide-induced cellular immunotherapy to induce cytotoxic T cells to peptides containing point mutant p53, or other oncogene products, thus potentially inducing tumor-specific cellular immunity. There are many potential prerequisites for successful immunotherapeutic targeting of intracellular antigens such as p53, including: (1) the protein must have a sufficient expression level; (2) it should be a candidate for proteolytic degradation and transport into the ER; (3) the tumor-specific epitope must have adequate affinity to the corresponding MHC restriction element; (4) the MHC complex must be expressed at sufficient levels on the cell surface to make the tumor-specific epitope accessible to T cells; and (5) the method of therapeutic immunization must effectively induce oncopeptide-specific cytotoxic T lymphocytes.     

Quantitative trait locus analysis of susceptibility to diet-induced atherosclerosis in recombinant inbred mice

Quantitative trait locus (QTL) analysis is a statistical method that can be applied to identify loci making a significant impact on a phenotype. For the phenotype of susceptibility to diet-induced atherosclerosis in the mouse, we have studied four quantitative traits: area of aortic fatty streaks and serum concentrations of high-density lipoprotein-bound cholesterol (HDL-cholesterol), apolipoprotein A-I, and apolipoprotein A-II (apo A-II). QTL analysis revealed a significant locus on chromosome 1 distal impacting serum apo A-II concentration on a high-fat diet and serum HDL-cholesterol concentration on a chow diet. This locus is presumablyApoa-2, the structural gene for apo A-II. QTL analysis of aortic fatty streaks failed to reveal a significant locus.     

Arthrostemma primaevum (Melastomataceae): A new species endemic to southeastern Mexico

Arthrostemma primaevum, a new species endemic to southeastern Mexico, is described, illustrated, and compared with its closest extant relative,A. ciliatum. The chromosome count ofn=15, reported here forA. primaevum, suggests thatA. ciliatum, withn=30, is a tetraploid derivative with a much broader geographic and elevational range. In addition to its distinctive unlobed staminal appendages and unique chromosome number,A. primaevum is notable for its shorter, urceolate hypanthium and seeds that have essentially smooth continuous semicircular ridges.     

The biogeochemistry of a north-temperate grassland with native ungulates: Nitrogen dynamics in Yellowstone National Park

Nutrient dynamics of large grassland ecosystems possessing abundant migratory grazers are poorly understood. We examined N cycling on the northern winter range of Yellowstone National Park, home for large herds of free-roaming elk (Cervus elaphus) and bison (Bison bison). Plant and soil N, net N mineralization, and the deposition of ungulate fecal-N were measured at five sites, a ridgetop, mid-slope bench, steep slope, valley-bottom bench, and riparian area, within a watershed from May, 1991 to April, 1992.Results indicated similarities between biogeochemical properties of Yellowstone grassland and other grassland ecosystems: (1) landscape position and soil water affected nutrient dynamics, (2) annual mineralization was positively related to soil N content, and (3) the proportion of soil N mineralized during the year was negatively related to soil C/N.Grazers were a particularly important component of the N budget of this grassland. Estimated rates of N flow from ungulates to the soil ranged from 8.1 to 45.6 kg/ha/yr at the sites (average = 27.0 kg/ha/yr), approximately 4.5 times the amount of N in senescent plants. Rates of nitrogen mineralization for Yellowstone northern range grassland were higher than those measured in other temperate grassland ecosystems, possibly due to grazers promoting N cycling in Yellowstone.