Harry Lenas

Taha Toros Arşivi, Dosya No: 112-Pastahaneler, Bozacılar, Gazozcular, Börekçiler, Turşucular, Sucularİstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

Rapid detection of hypoxia-inducible factor-1-active tumours: pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1alpha

PURPOSE: Hypoxia-inducible factor-1 (HIF-1) plays an important role in malignant tumour progression. For the imaging of HIF-1-active tumours, we previously developed a protein, POS, which is effectively delivered to and selectively stabilized in HIF-1-active cells, and a radioiodinated biotin derivative, (3-(123)I-iodobenzoyl)norbiotinamide ((123)I-IBB), which can bind to the streptavidin moiety of POS. In this study, we aimed to investigate the feasibility of the pretargeting method using POS and (123)I-IBB for rapid imaging of HIF-1-active tumours. METHODS: Tumour-implanted mice were pretargeted with POS. After 24 h, (125)I-IBB was administered and subsequently, the biodistribution of radioactivity was investigated at several time points. In vivo planar imaging, comparison between (125)I-IBB accumulation and HIF-1 transcriptional activity, and autoradiography were performed at 6 h after the administration of (125)I-IBB. The same sections that were used in autoradiographic analysis were subjected to HIF-1alpha immunohistochemistry. RESULTS: (125)I-IBB accumulation was observed in tumours of mice pretargeted with POS (1.6%ID/g at 6 h). This result is comparable to the data derived from (125)I-IBB-conjugated POS-treated mice (1.4%ID/g at 24 h). In vivo planar imaging provided clear tumour images. The tumoral accumulation of (125)I-IBB significantly correlated with HIF-1-dependent luciferase bioluminescence (R=0.84, p<0.01). The intratumoral distribution of (125)I-IBB was heterogeneous and was significantly correlated with HIF-1alpha-positive regions (R=0.58, p<0.0001). CONCLUSION: POS pretargeting with (123)I-IBB is a useful technique in the rapid imaging and detection of HIF-1-active regions in tumours

Caluculation of Eigenmodes for Dielectric load Groove Guide -Based on Dielectric load planar circuit and transverse equivalent network-

rights: 社団法人電子情報通信学会　2002年電子情報通信学会総合大会　2002年3月27日～30日　早稲田大学　理工学部　大久保キャンパ

Truncated KCNQ1 mutant, A178fs/105, forms hetero-multimer channel with wild-type causing a dominant-negative suppression due to trafficking defect

AbstractWe identified a novel mutation Ala178fs/105 missing S3–S6 and C-terminus portions of KCNQ1 channel. Ala178fs/105-KCNQ1 expressed in COS-7 cells demonstrated no current expression. Co-expression with wild-type (WT) revealed a dominant-negative effect, which suggests the formation of hetero-multimer by mutant and WT. Confocal laser microscopy displayed intracellular retention of Ala178fs/105-KCNQ1 protein. Co-expression of the mutant and WT also increased intracellular retention of channel protein compared to WT alone. Our findings suggest a novel mechanism for LQT1 that the truncated S1–S2 KCNQ1 mutant forms hetero-multimer and cause a dominant-negative effect due to trafficking defect

Membrane proteins Bqt3 and -4 anchor telomeres to the nuclear envelope to ensure chromosomal bouquet formation

A screen identifies two more bouquet proteins required for meiotic telomere clustering: Bqt4 anchors the telomeres, whereas Bqt3 protects Bqt4 from degradation

Conduction-band electronic states of YbInCu4 studied by photoemission and soft x-ray absorption spectroscopies

We have studied conduction-band (CB) electronic states of a typical valence-transition compound YbInCu4 by means of temperature-dependent hard x-ray photoemission spectroscopy (HX-PES) of the Cu 2p3/2 and In 3d5/2 core states taken at hν=5.95 keV, soft x-ray absorption spectroscopy (XAS) of the Cu 2p3/2 core absorption region around hν∼935 eV, and soft x-ray photoemission spectroscopy (SX-PES) of the valence band at the Cu 2p3/2 absorption edge of hν=933.0 eV. With decreasing temperature below the valence transition at TV=42 K, we have found that (1) the Cu 2p3/2 and In 3d5/2 peaks in the HX-PES spectra exhibit the energy shift toward the lower binding-energy side by ∼40 and ∼30 meV, respectively, (2) an energy position of the Cu 2p3/2 main absorption peak in the XAS spectrum is shifted toward higher photon-energy side by ∼100 meV, with an appearance of a shoulder structure below the Cu 2p3/2 main absorption peak, and (3) an intensity of the Cu L3VV Auger spectrum is abruptly enhanced. These experimental results suggest that the Fermi level of the CB-derived density of states is shifted toward the lower binding-energy side. We have described the valence transition in YbInCu4 in terms of the charge transfer from the CB to Yb 4f states

Decreases in the Serum VLDL-TG/Non-VLDL-TG Ratio from Early Stages of Chronic Hepatitis C: Alterations in TG-Rich Lipoprotein Levels

BACKGROUND: The liver secretes very-low-density lipoproteins (VLDLs) and plays a key role in lipid metabolism. Plasma total triglyceride (TG) level variations have been studied in patients with hepatitis C virus (HCV)-related chronic hepatitis (CH-C). However, the results of these studies are variable. A homogenous assay protocol was recently proposed to directly measure the TG content in VLDL (VLDL-TG) and VLDL remnants. METHODOLOGY/PRINCIPAL FINDINGS: Using the assay protocol, we determined serum VLDL-TG levels in 69 fasting patients with biopsy-proven HCV-related chronic liver disease and 50 healthy subjects. Patients were classified into stages F0-F4 using the 5-point Desmet scale. Serum total TG levels in patients with non-cirrhotic (F1-F3) CH-C did not demonstrate significant differences compared with healthy subjects, but serum VLDL-TG levels did demonstrate significant differences. Mean serum VLDL-TG levels tended to decrease with disease progression from F1 to F4 (cirrhosis). Compared with healthy subjects, serum non-VLDL-TG levels significantly increased in patients with stages F2 and F3 CH-C; however, we observed no significant difference in patients with liver cirrhosis. Furthermore, the serum VLDL-TG/non-VLDL-TG ratio, when taken, demonstrated a significant decrease in patients with CH-C from the mildest stage F1 onward. CONCLUSIONS/SIGNIFICANCE: The decrease in serum VLDL-TG levels was attenuated by increase in non-VLDL-TG levels in patients with non-cirrhotic CH-C, resulting in comparable total TG levels. Results of previous studies though variable, were confirmed to have a logical basis. The decrease in the serum VLDL-TG/non-VLDL-TG ratio as early as stage F1 demonstrated TG metabolic alterations in early stages of CH-C for the first time. The involvement of TG metabolism in CH-C pathogenesis has been established in experimental animals, while conventional TG measurements are generally considered as poor indicators of CH-C progression in clinical practice. The serum VLDL-TG/non-VLDL-TG ratio, which focuses on TG metabolic alterations, may be an early indicator of CH-C