Retinoid is a collective term which indicates vitamin A (retinol) and its derivatives. Retinoid has a variety of functions such as growth promotion, maintenance of reproduction and dark adaptation. Retinoid also regulates cell differentiation and tissue morphogenesis. Sinceabnormality in the differentiation induces cellular atypia and that of the morphogenesis induces structural atypia, retinoid has important effects which inhibit carcinogenesis.

Macrophages in atherosclerotic lesions accumulate free cholesterol (FC) as well as cholesteryl ester and appear to have high rates of phospholipid (PL) synthesis and increased PL mass. Previous short term (i.e. 24 h) studies with cultured macrophages have shown that these cells respond to FC loading by up-regulating phosphatidylcholine biosynthesis. We propose that this response is adaptive by keeping the FC:PL ratio in the macrophages from reaching toxic levels. We further propose that one cause of macrophage necrosis, a prominent and important event in atherosclerosis, is an eventual decrease of this adaptive response. To explore these ideas, cultured macrophages were loaded with FC for up to 4 days and assayed for phosphatidylcholine biosynthesis, FC and PL mass, and cytotoxicity. For the first 24 h, cellular phosphatidylcholine biosynthesis and FC and PL mass increased 3-4-fold, and thus the FC:PL molar ratio was prevented from reaching very high levels; at this point, there were no overt signs of cytotoxicity. Over the next 24 -48 h, however, phosphatidylcholine biosynthesis, and then phosphatidylcholine mass, began to decrease. Initially, the macrophages remained healthy and continued to accumulate FC, but eventually these macrophages, but not unloaded macrophages, became necrotic (swollen organelles and disrupted membranes). Lipoprotein dose studies indicated a close relationship between the onset of macrophage necrosis and the FC:PL ratio. To test further the causal nature of these relationships, cellular FC and PL mass were independently manipulated by using high density lipoprotein 3 (HDL 3 ) to decrease cellular FC and choline depletion to decrease cellular PC. As predicted by our hypotheses, HDL 3 protected FC-loaded macrophages from necrosis, whereas choline depletion accelerated cytotoxic changes. These findings support the idea that the initial increase in phosphatidylcholine biosynthesis in FC-loaded macrophages is an adaptive response that prevents cholesterol-induced macrophage necrosis. We propose that an eventual failure of the PL response in foam cells may represent one cause of macrophage necrosis in advanced atherosclerotic lesions.

When LBW, rather than TBW or BV, is used, the iodine dose required to achieve consistent hepatic enhancement may be estimated more precisely and with reduced patient-to-patient variability.

Oral administration with acyclic retinoid, a synthetic vitamin A analog, for a limited period of 12 months (48 weeks) prevented the development of second primary hepatocellular carcinoma (HCC) and also improved the survival of patients who underwent curative treatments of the initial tumor. Following that randomized controlled study reported in 1996 and 1999, we have continued to follow up the patients by medical imaging and blood chemical analyses, and found that the preventive effect of acyclic retinoid lasted up to 199 weeks after randomization (or 151 weeks after completion of retinoid administration). The retinoid’s effect was not mediated by reduction in hepatic necro-inflammation since no significant decrease in serum aminotransferase activity was seen in the retinoid group. Such observation seems quite distinct from the cancer-preventive mechanism of interferon, a potent immunopreventive agent for HCC. We have also shown here the reduction by the retinoid in serum levels of lectin-reactive α-fetoprotein (AFP-L3) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), both of which indicate the presence of latent HCC cells. These results suggest that acyclic retinoid may delete such malignant clones before they expand to clinically detectable tumors and thereby inhibited second primary HCC. Once such latent clones are eradicated, it may well take at least several years for the next cancer clone to arise clinically. This may possibly explain a reason for the long-term effect of the retinoid even after the limited period of administration.

Purpose:To determine the optimal b values required for diffusion-weighted (DW) imaging of the liver in the detection and characterization of benign and malignant hepatic lesions. Materials and Methods:MR images obtained in 76 patients including 28 malignant hepatic lesions (21 hepatocellular carcinomas and 7 metastases) and 27 benign lesions (12 hemangiomas and 15 cysts) were reviewed. DWecho planner images (EPIs; b values with100, 200, 400, and 800 s/mm 2 ) were reviewed solely first, and then with T2-weighted EPIs (b ϭ 0 s/mm 2 ).Results: Sensitivity for malignant lesions (74%) was highest on DW-EPIs with b value of 100 s/mm 2 and T2-weighted EPIs combined (P Ͻ 0.05), and sensitivity for benign lesions (87%) was highest on DW-EPIs with b value of 800 s/mm 2 and T2-weighted EPIs (P Ͻ 0.05). Specificities were comparably high for all sequences. The Az values for malignant lesions were 0.94, 0.90, 0.87, and 0.89, and those for benign lesions were 0.91, 0.89, 0.87, and 0.94 on DW-EPIs with b values of 100, 200, 400, and 800 and T2-weighted EPIs combined, respectively. Hepatic cysts were clearly distinguished with the cutoff ADC value of 2.5 ϫ10 Ϫ3 mm 2 /s using a b value of 400 s/mm 2 or greater.Conclusion: DW-EPIs with middle b values were not required in the detection and characterization of benign and malignant hepatic lesions.