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Our previous studies have shown that human mesangial cells (HMCs) incubated with fibrogenic glomerulopathic monoclonal light chains (G-LCs) obtained from the urine of patients with light chain deposition disease produce increased extracellular matrix (ECM) when compared with HMCs not exposed to fibrogenic LCs. This overproduction of ECM proteins is regulated by transforming growth factor-beta (TGF-beta); blocking TGF-beta normalizes the production of ECM proteins. All ECM proteins, after synthesis, have to go through the secretory pathway in the endoplasmic reticulum (ER) and Golgi complex for final maturation and secretion. Blocking the secretory pathway may reduce the accumulation of ECM proteins. We tested the effect of tunicamycin, a specific inhibitor of N-linked glycosylation in the ER which inhibited glycosylation and brefeldin A, an inhibitor of vesicle transport between the endoplasmic reticulum and the Golgi complex, on ECM protein production, both resulting in subsequent upregulation of glucose-regulated protein 78. Overproduction of fibronectin and tenascin by HMCs was normalized by tunicamycin and brefeldin A. Similarly, when HMCs were exposed to exogenous TGF-beta, the increase in fibronectin was reversed by tunicamycin and brefeldin A. Exogenous platelet-derived growth factor-beta (PDGF-beta) did not induce fibronectin overproduction but significantly stimulated proliferation of HMCs. In summary, this study further supports the notion that fibrogenic G-LCs promote the accumulation of ECM proteins, through the actions of TGF-beta. Importantly, the data indicate that altering protein trafficking in the ER results in impairment of secretion of proteins into the ECM. Furthermore, the data also reveal that PDGF-beta and TGF-beta act independently and that PDGF-beta activation by itself cannot increase ECM proteins directly, but only by increasing the number of HMCs., (Copyright 2003 S. Karger AG, Basel)

1,066 urine samples were assayed by beta-human chorionic gonadotrophin (beta-hCG) monoclonal pregnancy test with a sensitivity of 150 IU hCG/l. Tests were performed in 5 independent laboratories and results were compared with those of pregnancy tests which were used routinely. Urine samples which showed discordant results under evaluation were reassayed for beta-hCG using radioimmunoassay. 569 urine samples were from nonpregnant women, and a consistent result with comparison pregnancy tests was achieved in 97.19% of urine samples. The trial test from 389 urine samples of pregnant women was 99.49% in accordance with routine pregnancy tests. Results from 108 urine samples of women over 40 years of age indicate the high specificity of the new beta-hCG monoclonal pregnancy test. Titration experiments showed 63% positive tests at 150 IU beta-hCG/l. Data presented combine to suggest that this new monoclonal pregnancy test is a valuable aid in diagnosing early pregnancy. It may also be used in the diagnosis of tubal pregnancy and in other ectopic processes.