Clinicopathologic and Prognostic Significance of Multiple Hormone Expression in Pancreatic Neuroendocrine Tumors

Kim, Joo Young,Kim, Min-Sun,Kim, Ki-Suk,Song, Ki-Byung,Lee, Seung Hun,Hwang, Dae Wook,Kim, Kyu-pyo,Kim, Hyoung Jung,Yu, Eunsil,Kim, Song Cheol,Jang, Hyeung-Jin,Hong, Seung-Mo Wolters Kluwer Health, Inc. All rights reserved. 2015 The American journal of surgical pathology Vol.39 No.5

Pancreatic neuroendocrine tumors (PanNETs) produce variable peptide hormones. The expression status of some hormones has been linked to the biological and clinical behaviors of PanNETs. A total of 226 surgically resected PanNETs were selected. Immunolabeling for peptide hormones was compared with various clinicopathologic factors, including patient survival. Expression of insulin, glucagon-like peptide 1, glucagon, gastrin, somatostatin, and serotonin were observed in 56 (24.8%), 41 (18.1%), 25 (11.1%), 5 (2.2%), 5 (2.2%), and 4 (1.8%) cases, respectively. Expression of 1, 2, and 3 hormones was noted in 70 (31.0%), 28 (12.4%), and 3 (1.3%) cases, respectively; 125 cases (55.3%) were negative for all hormones. PanNETs with insulin and glucagon-like peptide 1 expression were associated with a lower grade, smaller size, lower pT and pN classifications, absence of lymphovascular invasion, and lymph node metastasis and had better survival by univariate analysis, whereas PanNETs with gastrin expression were associated with a higher grade, larger size, higher pT and pN classifications, presence of lymphovascular invasion, and lymph node metastasis and had worse survival. Gastrin expression, increased age, and tumor grade were negative prognostic factors in multivariate analysis. As the number of hormones expressed increased, the survival rate of PanNET patients increased. In summary, PanNET patients showing insulin or glucagon-like peptide 1 expression and increased numbers of expressed hormones had a better survival outcome by univariate analysis, whereas gastrin expression was a negative prognostic indicator in surgically resected PanNET patients.

Distribution of HLA-DQA1^*01, ^*03, ^*05 and DQB1^*02 Subtypes and the Associated Haplotypes in the Korean Population

Pyo, Chul-Woo,Chung, Seo-Young,Hur, Seong-Suk,Kim, Hyoung-Jae,Choi, Jee-Yeoun,Kim, Yang-Kyum,Yoo, Ha-Jung,Choi, Hee-Baeg,Kim, Tai-Gyu The Korean Association of Immunobiologists 2003 Immune Network Vol.3 No.2

Background: As all HLA class II genes, the DQ genes show their polymorphic variation mainly in the second exon, which encodes the first extracellular domain of the molecule. PCR-SSOP (Polymerase chain reaction-Sequence specific oligonucleotide probe) techniques were frequently used for HLA-DQA1 and DQB1 typing but certain alleles, $DQA1^*0101/0104/0105$, $^*302/0303$, $*0501/0505$ and $DQB1^*0201/^*0202$ which differ from each other in segment other than exon 2, could not be unequivocally assigned. Methods: To overcome this problem, we applied additional PCR-SSP (PCR-Sequence specific primer) method to analyze DQA1 exons 1, 3 and 4 and DQB1 exon 3. And we investigated the distributions and haplotypes of HLA-DRB1, DQA1 and DQB1 alleles in 406 unrelated Korean healthy individuals. Results: Using this method the indistinguishable alleles of DQA1 and DQB1 in PCR-SSOP were typed definitively. We also found several important associations between DQA1 and DQB1 alleles in the Korean population; $DQA1^*0101-DQB1^*0501$, $DQA1^*0104-DQB1^*0502$ or $-^*0503$, $DQA1^*0105-DQB1^*0501$, $DQA1^*0302-DQB1^*0303$, $DQA1^*0303-DQB1^*0401$ or $-^*0402$, $DQA1^*0501-DQB1^*0201$, $DQA1^*0505-DQB1^*0301$, and $DQA1^*0201-DQB1^*0202$. The haplotypes of DRB1-DQA1-DQB1 associated with $DQA1^*01$, $^*03$, $^*05$, and $DQB1^*02$ subtypes were investigated. Several haplotypes associated with these alleles were observed in the Korean population. Conclusion: Our results can be helpful to find potential unrelated donors for bone marrow registries and study the HLA-associated disease and anthropology at high-resolution allelic level.

S5a promotes protein degradation by blocking synthesis of nondegradable forked ubiquitin chains

Kim, Hyoung Tae,Kim, Kwang Pyo,Uchiki, Tomoaki,Gygi, Steven P,Goldberg, Alfred L Wiley (John WileySons) 2009 The EMBO journal Vol.28 No.13

<P>Ubiquitin (Ub)-protein conjugates formed by purified ring-finger or U-box E3s with the E2, UbcH5, resist degradation and disassembly by 26S proteasomes. These chains contain multiple types of Ub forks in which two Ub's are linked to adjacent lysines on the proximal Ub. We tested whether cells contain factors that prevent formation of nondegradable conjugates and whether the forked chains prevent proteasomal degradation. S5a is a ubiquitin interacting motif (UIM) protein present in the cytosol and in the 26S proteasome. Addition of S5a or a GST-fusion of S5a's UIM domains to a ubiquitination reaction containing 26S proteasomes, UbcH5, an E3 (MuRF1 or CHIP), and a protein substrate, dramatically stimulated its degradation, provided S5a was present during ubiquitination. Mass spectrometry showed that S5a and GST-UIM prevented the formation of Ub forks without affecting synthesis of standard isopeptide linkages. The forked Ub chains bind poorly to 26S proteasomes unlike those synthesized with S5a present or linked to Lys63 or Lys48 chains. Thus, S5a (and presumably certain other UIM proteins) function with certain E3/E2 pairs to ensure synthesis of efficiently degraded non-forked Ub conjugates.</P>

Human neurospheres derived from the fetal central nervous system are regionally and temporally specified but are not committed

Kim, Hyoung-Tai,Kim, Il-Sun,Lee, Il-Shin,Lee, Jean-Pyo,Snyder, Evan Y.,In Park, Kook Elsevier 2006 Experimental neurology Vol.199 No.1

<P><B>Abstract</B></P><P>Proliferating single cells were isolated from various CNS regions (telencephalon, diencephalon, midbrain, cerebellum, pons and medulla, and spinal cord) of human fetal cadavers at 13 weeks of gestation and grown as neurospheres in long-term cultures. We investigated whether neural stem cells (NSCs) or progenitors within spheres have specific regional or temporal characteristics with regard to growth, differentiation, and region-specific gene expression, and whether these molecular specifications are reversible. Regardless of regional origin, all of the neurospheres were found to contain cells of different subtypes, which suggests that multipotent NSCs, progenitors or radial glial cells co-exist with restricted neuronal or glial progenitors within the neurospheres. Neurospheres from the forebrain grew faster and gave rise to significantly more neurons than did those from either the midbrain or hindbrain, and regional differences in neuronal differentiation appeared to be sustained during long-term passage of neurospheres in culture. There was also a trend towards a reduction in neuronal emergence from the respective neurospheres over time in culture, although the percentages of neurons generated from cerebellum-derived neurospheres increased dramatically. These results suggest that differences in neuronal differentiation for the various neurospheres are spatially and temporally determined. In addition, the properties of glial fibrillary acidic protein (GFAP)-, glutamate-, and γ-aminobutyric acid (GABA)-expressing cells derived from neurospheres of the respective CNS regions appear to be regionally and temporally different. Isolated human neurospheres from different CNS compartments expressed distinctive molecular markers of regional identity and maintained these patterns of region-specific gene expression during long-term passage in vitro. To determine the potential of human neurospheres for regional fate plasticity, single spheres from the respective regions were co-cultured with embryonic day 16.5 (E16.5 d) mouse brain slices. Specific cues from the developing mouse brain tissues induced the human neurospheres to express different marker genes of regional identity and to suppress the expression of their original marker genes. Thus, even the early regional identities of human neurospheres may not be irreversible and may be altered by local inductive cues. These findings have important implications for understanding the characteristics of growth, differentiation, and molecular specification of human neurospheres derived from the developing CNS, as well as the therapeutic potential for neural repair.</P>

Accelerated Life Testing Method of Transmission

Kim, Hyoung Eui,Kim, Doh Sik,Lee, Yoon Pyo,Yoo, Yung Chul Trans Tech Publications, Ltd. 2006 Key Engineering Materials Vol.326 No.-

<P>In this study, we proposed a process of an accelerated life testing method of 5-speed manual transmissions used in vehicles, which loads are consisted of multiple alternating loads. The entire process of an 5-speed manual transmission’s accelerated life testing method where no failures are allowed, is a process that requires an abundance of assumptions, and other factors that are estimates such as the shape parameter, beta() and the fatigue damage exponent (x). And the process is consisted of 7-step process. From the 1-setp, which is the deriving the service(use) torque and speed(rpm) profile of the transmission, to the 7-step, we could determine the accelerated life time, the accelerated torque and the accelerated speed(rpm), which are the equivalent cumulative fatigue damage. Also, we have performed accelerated life test on 5-speed manual transmission by using the following 7-step process.</P>

Physically Based Nonrigid Registration Using Smoothed Particle Hydrodynamics: Application to Hepatic Metastasis Volume-Preserving Registration

Pyo, Soon Hyoung,Lee, Jeongjin,Park, Seongjin,Kim, Kyoung Won,Shin, Yeong-Gil,Kim, Bohyung IEEE 2013 IEEE Transactions on Biomedical Engineering Vol.60 No.9

<P>Recent advances in computing hardware have enabled the application of physically based simulation techniques to various research fields for improved accuracy. In this paper, we present a novel physically based nonrigid registration method using smoothed particle hydrodynamics for hepatic metastasis volume-preserving registration between follow-up liver CT images. Our method models the liver and hepatic metastasis as a set of particles carrying their own physical properties. Based on the fact that the hepatic metastasis is stiffer than other normal cells in the liver parenchyma, the candidate regions of hepatic metastasis are modeled with particles of higher stiffness compared to the liver parenchyma. Particles placed in the liver and candidate regions of hepatic metastasis in the source image are transformed along a gradient vector flow-based force field calculated in the target image. In this transformation, the particles are physically interacted and deformed by a novel deformable particle method which is proposed to preserve the hepatic metastasis to the best. In experimental results using ten clinical datasets, our method matches the liver effectively between follow-up CT images as well as preserves the volume of hepatic metastasis almost completely, enabling the accurate assessment of the volume change of the hepatic metastasis. These results demonstrated a potential of the proposed method that it can deliver a substantial aid in measuring the size change of index lesion (i.e., hepatic metastasis) after the chemotheraphy of metastasis patients in radiation oncology.</P>

CCCTC-binding factor is essential to the maintenance and quiescence of hematopoietic stem cells in mice

Kim, Tae-Gyun,Kim, Sueun,Jung, Soyeon,Kim, Mikyoung,Yang, Bobae,Lee, Min-Geol,Kim, Hyoung-Pyo Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.8

<P>Hematopoiesis involves a series of lineage differentiation programs initiated in hematopoietic stem cells (HSCs) found in bone marrow (BM). To ensure lifelong hematopoiesis, various molecular mechanisms are needed to maintain the HSC pool. CCCTC-binding factor (CTCF) is a DNA-binding, zinc-finger protein that regulates the expression of its target gene by organizing higher order chromatin structures. Currently, the role of CTCF in controlling HSC homeostasis is unknown. Using a tamoxifen-inducible CTCF conditional knockout mouse system, we aimed to determine whether CTCF regulates the homeostatic maintenance of HSCs. In adult mice, acute systemic CTCF ablation led to severe BM failure and the rapid shrinkage of multiple c-Kit<SUP>hi</SUP> progenitor populations, including Sca-1<SUP>+</SUP> HSCs. Similarly, hematopoietic system-confined CTCF depletion caused an acute loss of HSCs and highly increased mortality. Mixed BM chimeras reconstituted with supporting BM demonstrated that CTCF deficiency-mediated HSC depletion has both cell-extrinsic and cell-intrinsic effects. Although c-Kit<SUP>hi</SUP> myeloid progenitor cell populations were severely reduced after ablating <I>Ctcf</I>, c-Kit<SUP>int</SUP> common lymphoid progenitors and their progenies were less affected by the lack of CTCF. Whole-transcriptome microarray and cell cycle analyses indicated that CTCF deficiency results in the enhanced expression of the cell cycle-promoting program, and that CTCF-depleted HSCs express higher levels of reactive oxygen species (ROS). Importantly, <I>in vivo</I> treatment with an antioxidant partially rescued c-Kit<SUP>hi</SUP> cell populations and their quiescence. Altogether, our results suggest that CTCF is indispensable for maintaining adult HSC pools, likely by regulating ROS-dependent HSC quiescence.</P>

Multi-waveform fast-scan cyclic voltammetry mapping of adsorption/desorption kinetics of biogenic amines and their metabolites

Kim, Do Hyoung,Oh, Yoonbae,Shin, Hojin,Park, Cheonho,Blaha, Charles D.,Bennet, Kevin E.,Kim, In Young,Lee, Kendall H.,Jang, Dong Pyo The Royal Society of Chemistry 2018 Analytical methods Vol.10 No.24

<P>Fast-scan cyclic voltammetry (FSCV) is an effective method for investigating electro-active neurochemical species. In recent years, FSCV has been used to measure electro-active neurotransmitters in a variety of neuroscience studies. We previously reported on the use of paired-pulse voltammetry (PPV) that enables FSCV to differentiate various analytes and minimize confounding factors by taking advantage of the adsorption characteristics of the analyte on carbon fiber microelectrodes. In spite of a number of studies regarding adsorption/desorption characteristics of neurotransmitters, the difference in adsorption/desorption properties among neurotransmitters has yet to be fully explored. To calculate adsorption/desorption constants for neurotransmitters, we propose the use of multi-waveform FSCV (M-FSCV), which consists of ten triangular waveforms in a single scan. Within the multiple waveforms, the voltammetric response of dopamine decayed exponentially because of the decreased adsorption time period. The decay pattern was mathematically described using adsorption/desorption characteristics and two additional initial points: an exponential decay constant (<I>K</I>) and an initial quantity (<I>A</I>), which were extracted from the decay equation. Using this method, we were able to quantify the decay constant (<I>K</I>-map) and an initial quantity (<I>A</I>-map) color plot in addition to a conventional pseudo color plot. M-FSCV was evaluated with two biogenic amine groups (catecholamines and indolamines) to characterize their inherent adsorption/desorption constants. As a result, the <I>A</I>-map showed a high correlation with concentration and the <I>K</I>-map for each group to be significantly differentiated. These results demonstrate that M-FSCV has the potential to be a useful technique for acquiring additional adsorption/desorption information regarding neurotransmitters.</P>

Sparing of fatty infiltration around focal hepatic lesions in patients with hepatic steatosis: sonographic appearance with CT and MRI correlation.

Kim, Kyoung Won,Kim, Min Ju,Lee, Seung Soo,Kim, Hyoung Jung,Shin, Yong Moon,Kim, Pyo-Nyun,Lee, Moon-Gyu American Roentgen Ray Society, etc.] 2008 American Journal of Roentgenology Vol.190 No.4

<P>The purposes of this study were to illustrate the sonographic features of focal hepatic lesions with peritumoral sparing of fatty infiltration in patients with hepatic steatosis, to correlate the sonographic findings with CT and MRI findings, and to discuss the possible mechanisms.</P>

Development of Engineered Fluorescent Antibodies for Effective Diagnosis and Immunotherapy

Jong Pyo KIM,Gyu Seong LEE,Shima Rizi YOUSEFI,Seon Hyoung KIM,Hee-Jin JEONG 한국생물공학회 2022 한국생물공학회 학술대회 Vol.2022 No.4