Fungal metabolic model for human type I hereditary tyrosinaemia.

Type I hereditary tyrosinaemia (HT1) is a severe human inborn disease resulting from loss of fumaryl-acetoacetate hydrolase (Fah). Homozygous disruption of the gene encoding Fah in mice causes neonatal lethality, seriously limiting use of this animal as a model. We report here that fahA, the gene encoding Fah in the fungus Aspergillus nidulans, encodes a polypeptide showing 47.1% identity to its human homologue, fahA disruption results in secretion of succinylacetone (a diagnostic compound for human type I tyrosinaemia) and phenylalanine toxicity. We have isolated spontaneous suppressor mutations preventing this toxicity, presumably representing loss-of-function mutations in genes acting upstream of fahA in the phenylalanine catabolic pathway. Analysis of a class of these mutations demonstrates that loss of homogentisate dioxygenase (leading to alkaptonuria in humans) prevents the effects of a Fah deficiency. Our results strongly suggest human homogentisate dioxygenase as a target for HT1 therapy and illustrate the usefulness of this fungus as an alternative to animal models for certain aspects of human metabolic diseases.

Differential activation of proliferation and cytotoxicity in human T-cell lymphotropic virus type I Tax-specific CD8 T cells by an altered peptide ligand.

Human T-cell leukemia virus type I (HTLV-I) gives rise to a neurologic disease known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the pathogenesis of the disease is unknown, the presence of a remarkably high frequency of Tax-specific, cytotoxic CD8 T cells may suggest a role of these cells in the development of HAM/TSP. Antigen-mediated signaling in a CD8 T-cell clone specific for the Tax(11-19) peptide of HTLV-I was studied using analog peptides substituted in their T-cell receptor contact residues defined by x-ray crystallographic data of the Tax(11-19) peptide in the groove of HLA-A2. CD8 T-cell stimulation with the wild-type peptide antigen led to activation of p56lck kinase activity, interleukin 2 secretion, cytotoxicity, and clonal expansion. A Tax analog peptide with an alanine substitution of the T-cell receptor contact residue tyrosine-15 induced T-cell-mediated cytolysis without activation of interleukin 2 secretion or proliferation. Induction of p56lck kinase activity correlated with T-cell-mediated cytotoxicity, whereas interleukin 2 secretion correlated with [3H]thymidine incorporation and proliferation. Moreover, Tax peptide analogs that activated the tyrosine kinase activity of p56lck could induce unresponsiveness to secondary stimulation with the wild-type peptide. These observations show that a single amino acid substitution in a T-cell receptor contact residue of Tax can differentially signal CD8 T cells and further demonstrate that primary activation has functional consequences for the secondary response of at least some Tax-specific CD8 T cells to HTLV-I-infected target cells.

Safety assessment of Denver Type I and Standard Type II Barricades via full scale tests. Volume I: executive summary. Final report.

Federal Highway Administration, Office of Research and Development, Washington, D.C.

Safety assessment of Denver Type I and Standard Type II Barricades via full scale tests. Volume II. Final report.

Federal Highway Administration, Office of Research and Development, Washington, D.C.

Safety assessment of Denver Type I and Standard Type II Barricades via full scale tests : executive summary /

Mode of access: Internet.

Operator, organizational, direct and general support maintenance manual : heater, space, multifuel, with blower, 15,000 BTU/hr, (Hunter model UH-48C, type I), NSN 4520-01-010-0316.

Includes index.

Unit maintenance repair parts and special tools lists : loader, scoop type, DED, 4 x 4, articulated frame steer, 4 1/2 to 5 cu. yd., (CCE), Army model H100C RB, type I with 4 1/2 cu. yd. rock bucket, NSN 3805-01-052-9042, Army model H100C GPB, type II with 5 cu. yd. general purpose bucket, NSN 3805-01-052-9043.

Includes indexes.

Unit maintenance repair parts and special tools list : loader, scoop type, DED 4 x 4, articulated frame steer, 4 1/2 to 5 cu. yd., (CCE), with 4 1/2 cu. yd. rock bucket, NSN 3805-00-602-5006, Clark model 175B, type I and with 5 cu. yd. general purpose bucket, NSN 3805-00-602-5013 Clark model 175B, type II.

Includes indexes.

Intermediate direct support and intermediate general support maintenance repair parts and special tools lists ... : loader, scoop type, DED, 4 x 4, articulated, frame steer, 4 1/2 to 5 cu. yd., (CCE), Army model H100C RB, type I with 4 1/2 cu. yd. rock bucket ....

"October 1988."

Operators, organizational and direct support maintenance manual (including repair parts list) : refrigerator, prefabricated; panel type; w/o refrigerating equipment; military specifications MIL-R-10932, Type I, Class I and II, 600 cu ft, FSN 4110-269-5096 ... Type II, Class I and II ... 1600 cu ft, FSN 4110-618-8714.

Includes index.

Operator and organizational maintenance manual : refrigeration unit, mechanical, panel type, gasoline engine driven, 9000 Btu, type I, for semitrailer, refrigerator, 7 1/2 ton (Redmanson model RGP-9000), FSN 4110-935-1512 ... FSN 4110-935-5483.

"November 1974."

Organizational maintenance repair parts and special tools list : refrigeration unit, mechanical, panel type, gasoline engine driven, 9000 Btu, type I, for semitrailer, refrigerator, 7 1/2 ton (Redmanson model RGP-9000), NSN 4110-00-935-1512 ....

"March 1976."

Operator, organizational, direct support, and general support maintenance manual for air conditioner, vertical compact : type I, vertical, size C, 18,000 BTU/hr, class I, 208 volt, 3 phase, 50/60 hertz, Keco model F18T-2 : NSN 4120-00-168-1781.

"21 December 1979."

Operator and organizational maintenance manual : tank, steel, vertical, bolted, knockdown, sealed openings, standard bottom and roof, gasoline, oil, or water (type I-pol and potable water, type II-pol and non-potable water), 100 barrel capacity ... 10,000 barrel capacity ....

"May, 1974."

Operator, organizational, and direct support maintenance manual including repair parts and special tools lists : heaters, space, radiant type, portable (type I, model M1941, solid fuel) FSN 4520-257-4877, (type II, model M1941, liquid fuel) FSN 4520-927-4214, (Yukon model M1950, solid or liquid fuel) FSN 4520-287-3353 : heaters, immersion, liquid fuel fired, for corrugated cans ....

"December 1969."