Byung Il Yeh

Serum levels of angiopoietin-related growth factor are increased in metabolic syndrome.

Angiopoietin-related growth factor (AGF), a novel hepatokine, showed therapeutic implications in diabetic and obese animal models. Although the physiologic functions of human AGF have not yet been identified, serum levels of AGF displayed up-regulation in groups with diseases including preeclampsia and diabetes; and there was little association between genetic variability of AGF and metabolic syndrome-related phenotypes. We analyzed serum levels of AGF and other biochemical and anthropometric markers in 216 Korean persons--the numbers of healthy controls and those with metabolic syndrome were 138 and 78, respectively--to confirm research data from animal models. Women had higher AGF than men (265.01 vs 311.84 ng/mL, P = .003). This study showed that serum AGF levels were significantly higher in subjects with metabolic syndrome (325.89 ng/mL) than those in the healthy group (272.44 ng/mL) (P = .003). Among the components of metabolic syndrome, subjects with high waist circumference or decreased high-density lipoprotein cholesterol had significantly increased serum AGF (271.92 vs 313.68 ng/mL, P = .013; 271.01 vs 310.58 ng/mL, P = .023, respectively). According to multivariate regression analysis, metabolic syndrome itself and waist circumference could be used, in addition to sex and age, as predictors of serum AGF level. In conclusion, serum AGF levels were paradoxically increased in metabolic syndrome, in comparison with data from animal experiments and data on sex, age, and waist circumference. Metabolic syndrome can be a predictor of serum AGF level. Further studies are needed to explore the possibilities of compensatory up-regulation, or AGF resistance, to explain the physiologic roles of AGF in metabolic syndrome.

Nucleotide sequence variation in the hypervariable region of the hepatitis C virus in the sera of chronic hepatitis C patients undergoing controlled interferon-α therapy

Ten patients with hepatitis C virus (HCV) infection (experimental group) were treated with interferon‐α (IF‐α). Dosage was six million units per day for one week and then three times a week for another six months. Seven HCV‐infected patients (control group) did not receive IF‐α therapy. The hypervariable region (HVR) of HCV in the sera of patients was amplified by reverse transcription‐polymerase chain reaction (RT‐PCR), and the variation of amino acid sequence in this region was determined. Serum alanine aminotransferase (ALT) activities in five patients treated for six months with IF‐α fell to the normal range, when HCV was not detected in the sera of three patients. The nucleotide sequence variation in HVR of HCV in the sera of five patients who responded well to the IF‐α therapy was relatively less than that in another five patients who did not respond to IF‐α therapy and those in the control patients. These results indicate that the effectiveness of IF‐α therapy was related to the sequence variation of HVR of HCV. This may have resulted from the selection pressure by humoral antibodies directed to HVR of HCV. It is concluded that the higher rate of sequence variation in HVR of HCV was compatible with a lower degree of effectiveness of IF‐α therapy.

On the Role of Pore Helix in Regulation of TRPV5 by Extracellular Protons

The transient receptor potential channel TRPV5 is localized to the apical membrane of the distal renal tubule and plays an important role in the regulation of transepithelial Ca2+ reabsorption in kidney. We have previously reported that extracellular protons inhibit TRPV5 by binding to glutamate-522 (E522) in the extracellular domain of the channel. We suggested that E522 is an extracellular “pH sensor” and its titration by extracellular protons inhibits TRPV5 via conformational change(s) of the pore helix. We now report that mutation of a pore helix residue glutamate-535 to glutamine (E535Q) enhances the sensitivity of the channel to inhibition by extracellular protons (i.e., shifting the apparent pKa for inhibition by extracellular protons to the more alkaline extracellular pH). The enhancement of extracellular proton-mediated inhibition of E535Q mutant is also dependent on E522. We have also reported that intracellular acidification enhances the sensitivity of TRPV5 to inhibition by extracellular protons. We now find that modulation of the extracellular proton-mediated inhibition by intracellular acidification is preserved in the E535Q mutant. These results provide further support for the idea that pore helix is involved in the regulation of TRPV5 by extracellular protons. Inhibition of TRPV5 by extracellular protons may contribute to hypercalciuria in diseases associated with high acid load.

Suksin Lee, the First Ph.D. and Full-Time Professor of Biochemistry in Korea

www.eymj.org Suksin Lee was born on October 6, 1897 at Namchonri, Gageum-myeon, Daedong-county, Pyeongannam-do in North Korea, as son to father Myeong-se Lee and mother surnamed Kang of Gogsan. He was licensed as a medical doctor (License No. 446) on August 20 in 1921. Right after his graduation from the Gyeongseong College of Medicine in 1921, he had stayed in Japan for almost 5 months, and then, he went from Japan to Germany for an additional study abroad together with Seong-yong Lee. Guchung Jeong had collected a vast amount of data and information, including interviews with many people, in order to write his book Pioneers of Korean Healthcare. In this book, he selected Suksin Lee as one of the representative personalities, together with Il-jun Ryu and Il-seon Yun, in the discipline of medicine in the 1920s in Korea. Some of the records on Suksin Lee he left are as follows:

Mutation of Ha-ras Oncogene in Rat Salivary Gland Tumors Induced by DMBA.

PURPOSE The incidence of salivary gland tumor is approximately 2% among all head and neck tumors, of which malignant cases account for only about 5%. Much research has been performed in order to clarify the mechanism of oncogene activation, however salivary gland tumors remain understudied. We performed this study in order to characterize the ras gene in these tumors. MATERIALS AND METHODS We treated white rats with 7, 12-dimethylbenz[a]anthracene (DMBA) and confirmed the occurrence of salivary gland tumors after ten to thirty weeks. Isolated genomic DNAs from tumor tissues were added to NIH 3T3 cells. In order to detect Ha-ras mutations, we performed a two-step PCR-RFLP and 7analyzed the mutated sequences. RESULTS We induced salivary gland tumors by DMBA treatment in white rats. Isolated DNAs from the tumor tissues transformed the NIH 3T3 cells. Point mutations were observed in codons 12 and 61 of the Ha-ras oncogene. The total frequency of point mutations was 13.9% in DMBA-induced salivary gland tumors in rats. CONCLUSION Our results demonstrate that a variety of cancers ras oncogene mutations were also found in salivary gland tumors. We confirmed that a point mutation of the Ha-ras oncogene in a DMBA-induced salivary gland tumor occurs at a frequency of 13.9%.