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In order to further investigate the deleterious effects of GH overexpression, we generated a novel line of transgenic mice featuring stable and specific expression of bovine GH in the heart and striated muscle. A DNA construct, containing a region with promoter activity from the Long Terminal Repeat of Rous Sarcoma Virus (RSV-LTR) and the entire structural gene of bovine GH (bGH), was microinjected by standard techniques in male pronuclei of fertilized mice eggs. Transgenic mice expressed bGH mRNA in the heart and striated muscle starting at 5-6 weeks of age. They featured circulating levels of a 22 kDa form of bGH up to 700 ng/ml and enhanced growth starting at 6 weeks of age. No pathologic changes of the myocardium and striated muscle fibers, other than hypertrophy, were noticed, although severe glomerulosclerosis and liver alteration occurred in older mice. Future studies on this new line of transgenic GH mice and integration with the existing data might improve our understanding of the molecular mechanism underlying the detrimental effects of elevated GH levels on various organs and functions.

The frequency of renal vascular lesions (RVL) and their relevance in the progression of renal damage were evaluated by the Pathology Group of the "Gruppo Italiano per lo Studio della Nefrite Lupica" (GISNEL). Of 285 patients with lupus nephritis collected from 20 nephrology centers in Italy and classified according to World Health Organization (WHO) criteria, 79 cases (27.7%) with RVL were identified and classified as follows: (1) lupus vasculopathy (n = 27); (2) hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) malignant hypertension-like lesions (n = 24); (3) vasculitis (n = 8); (4) arterio-arteriosclerosis (n = 20). At the time of renal biopsy, patients with RVL had mean serum creatinine levels significantly higher than patients without RVL (201.8 +/- 195.9 mumol/L [2.2 +/- 2.2 mg/dL] v 108.1 +/- 108.0 mumol/L [1.2 +/- 1.2 mg/dL]; P less than 0.01). Hypertension was more frequent in patients with RVL than in those without (68.4% v 30.5%; P less than 0.01). The probability of kidney survival assessed according to the Kaplan-Meier method at 5 and 10 years was, respectively, 74.3% +/- 5.9% and 58.0% +/- 8.9% in patients with RVL, compared with 89.6% +/- 2.7% and 85.9% +/- 3.7% in patients without RVL. However, the two groups did not differ significantly as regards overall survival, the probability of survival at 5 and 10 years being 86.5% +/- 4.5% and 78.8% +/- 6.6% in patients with RVL and 92.2% +/- 2.2% and 83.3% +/- 4.4% in patients without RVL.(ABSTRACT TRUNCATED AT 250 WORDS)

Occurrence of renal involvement in Rheumatoid arthritis is uncommon; when present it has been attributed to amyloid or secondary effects of drugs. Nevertheless, recent observations seem to indicate the existence of primary renal lesions associated with the disease. The purpose of this paper is to review the data suggesting that the kidney can be directly involved in Rheumatoid arthritis. The main points of interest are the occurrence of glomerulonephritis and/or amyloidosis, the presence of vasculitis and other arterial changes, the existence of chronic interstitial nephritis and papillary necrosis and lesions associated with gold and penicillamine therapy.