Background: S100A12, also known as EN-RAGE (extracellular newly identified receptor for advanced glycation end products binding protein) is a ligand for RAGE, and has been proposed to contribute to the development of atherosclerosis. In this study, we examined the plasma S100A12 concentration in patients with ESRD and undergoing hemodialysis (HD) and evaluated the relation between S100A12 level and carotid intimal media thickness (IMT) by ultrasound. Methods: We measured plasma S100A12 concentration in 72 HD patients and 42 control subjects. IMT of the carotid artery was measured by high-resolution B-mode ultrasonography in 46 HD patients. Results: The mean plasma S100A12 level was 2.3-fold higher in HD patients than in control subjects (25.0 ± 2.32 vs. 10.7 ± 0.97 ng/ml, p < 0.001). Stepwise multiple regression analysis identified circulating white blood cell count as a positive independent determinant and total cholesterol and serum albumin levels as negative independent determinants of plasma S100A12 concentration. The maximum IMT was positively correlated with plasma S100A12 level. Stepwise multiple regression analysis also identified plasma S100A12 as a significant independent determinant of the maximum IMT. Conclusion: These findings suggest that S100A12 protein is involved in the acceleration of atherosclerosis in HD patients.

In order to elucidate the role of the two disulfide linkages of tachyplesin I (T-SS), a membrane-acting cyclic antimicrobial peptide from Tachypleus tridentatus, we synthesized the acyclic analog (T-Acm) with the four SH groups protected by acetamidomethyl groups and also investigated the interactions of these peptides with lipid bilayers. T-SS induced leakage of calcein from egg yolk L-alpha-phosphatidylglycerol large unilamellar vesicles (PG LUVs) at peptide concentrations 1 order of magnitude smaller than those at which leakage was induced by T-Acm, which coincides with the stronger antimicrobial activities of T-SS. The micellization of PG LUVs was also more efficient for the cyclic peptide. Fluorescence titration studies revealed that binding affinities of both peptides to the PG membranes were similar. Fourier transform infrared polarized attenuated total reflection spectroscopy and fluorescence quenching experiments demonstrated that T-SS and T-Acm both form amphiphilic antiparallel beta-sheet structures in the membranes. They are formed in such a way that the sheet planes lie parallel to the membrane surface with the sheet hydrophobic surfaces penetrating slightly into the hydrophobic region of the bilayers. Furthermore, the observation that the linear T-Acm, the weaker membrane permeabilizer, caused a far more serious membrane disruption suggests the possibility that the mechanisms of membrane permeabilization by the cyclic peptide are different from those by the linear peptide, the latter being the disruption of the lipid organization.

The antitumor effects of SM‐5887, a totally synthetic 9‐aminoanthracycline derivative, were evaluated in six murinc experimental tumor systems (P38S, Ehrlich carcinoma, sarcoma 180, Lewis lung carcinoma, B16 melanoma and colon 38) and nine human tumor‐nude mouse systems (one breast cancer, two lung cancers and six gastric cancers). Characteristically SM‐5887 showed excellent antitumor activities, superior to adriamycin (ADR), against human tumor xenografts, although its activities against murine experimental tumors were almost equal to those of ADR. When the human tumors were implanted sc in female athymic mice (BALB/c, nu/nu) and their volume reached 100‐ 300 mm3, SM‐5887 and ADR were injected iv. All nine human tumors tested showed statistically significant responses to SM‐5887, and 7 of them were strongly suppressed in their growth by SM‐5887 so that minimum T/C values were less than 30% at the maximum tolerated dose (MTD, 25 mg/kg) with a single iv injection. Compared with ADR, SM‐5887 was statistically more effective in five tumors (one breast, one lung and three gastric), equal in two tumors (two gastric), and less potent in two tumors (one lung and one gastric). In addition, the 10‐day‐interval repeated iv treatments with SM‐5887 at the MTD (25 mg/kg) resulted in remarkably potent antitumor effects (including complete regression) against human gastric cancer, 4‐1ST, implanted in nude mice without enhancement of toxic effects, SM‐5887 was also effective against ip‐inoculated P388 by oral administration as well as iv injection.

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In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only ten cases are reported in the English literature. Herein, we describe the case of a 64-year-old man with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy showed diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study revealed positive staining for IgG, C3, and C1q along the renal tubular basement membrane (TBM). Electron microscopy also showed electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection, were ruled out. Taking these findings together with the presence of antitubular basement membrane antibody, predominant tubulointerstitial lupus nephritis was diagnosed. Treatment with oral corticosteroids for 6 weeks improved renal function. Even after tapering of the corticosteroid, renal function and serological markers of SLE activity have remained stable in this patient for more than 12 months.