Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.

Transgenic Caenorhabditis elegans expressing jellyfish Green Fluorescent Protein under the control of the promoter for the inducible small heat shock protein gene hsp-16-2 have been constructed. Transgene expression parallels that of the endogenous hsp-16 gene, and, therefore, allows direct visualization, localization, and quantitation of hsp-16 expression in living animals. In addition to the expected upregulation by heat shock, we show that a variety of stresses, including exposure to superoxide-generating redox-cycling quinones and the expression of the human beta amyloid peptide, specifically induce the reporter transgene. The quinone induction is suppressed by coincubation with L-ascorbate. The ability to directly observe the stress response in living animals significantly simplifies the identification of both exogenous treatments and genetic alterations that modulate stress response, and possibly life span, in C. elegans.

Transgenic Caenorhabditis elegans animals have been engineered to express wild-type and singleamino acid variants of a long form of human /3-amyloid peptide (A/3 1-42). These animals express high levels (~3OOng of A/3/mg of total protein) of apparently fulllength peptide, as determined by quantitative immunoblot. Expression of wild-type Afi in these animals leads to rapid production of amyloid deposits reactive with Congo red and thioflavin S. This model system has been used to examine the effect of Leu 17Pro, Leu17Val, Ala30-Pro, Met35Cys, and Met35Leu substitutions on the in vivo production of amyloid deposits. We find that the Leu17 Pro and Met 35Cys substitutions completely block the formation of thioflavin S-reactive deposits, implicating these as key residues for in vivo amyloid formation. We have also constructed transgenic strains expressing a novel A/I variant, the single-chain dimer. Animals expressing high levels of this variant also fail to produce thioflavin S-reactive deposits. Key Words: Caenorhabditis elegans-Transgenic-/3-Amyloid peptide-/3-Amyloid peptide variant-Aggregation.

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To study the possible mechanisms involved in growth retardation associated with hypothyroidism, serum T4, GH, the GH-dependent somatomedin, insulin-like growth factor (IGF), and its carrier protein (CP) were measured in hypothyroid rats and their age-matched controls. Three groups of rats were studied: infant, immature, and adult. Marked hypothyroidism (serum T4, less than 1 microgram/dl) was produced in experimental animals by providing them with drinking water containing 0.05% propylthiouracil. Infant and immature hypothyroid rats weighed markedly less than normal controls and had significantly reduced serum levels of GH, IGF, and CP. Normal adult rats, treated with propylthiouracil for 60 days, also weighed considerably less than control animals and exhibited a significant drop in serum GH, IGF, and CP during this period. The administration of bovine GH to hypothyroid adult rats for 7 days did not restore either IGF or CP levels to normal, indicating that their decrease in serum was, in part, a direct result of hypothyroidism per se. These results indicate that serum levels of GH, IGF, and CP are at least partly under thyroid hormone control. Furthermore, these studies suggest that the growth retardation associated with hypothyroidism may be mediated through somatomedin activity.

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