Damping index of Doppler hepatic vein waveform to assess the severity of portal hypertension and response to propranolol in liver cirrhosis: a prospective nonrandomized study

Kim, Moon Young,Baik, Soon Koo,Park, Dong Hun,Lim, Dae Wook,Kim, Jae Woo,Kim, Hyun Soo,Kwon, Sang Ok,Kim, Young Ju,Chang, Sei Jin,Lee, Samuel S. Wiley-Blackwell Publishing 2007 Liver International Vol. No.

<P>Abstract</P><P>Background and Aims</P><P>Alterations in the Doppler hepatic vein (HV) waveform are associated with cirrhosis and portal hypertension. We prospectively evaluated the correlation between the extent of abnormal Doppler HV waveforms expressed as damping index (DI) and the hepatic venous pressure gradient (HVPG) and response to propranolol in patients with cirrhosis.</P><P>Material and Methods</P><P>In 76 patients with cirrhosis (69 men and seven women), both DI of Doppler HV waveform and HVPG were measured, and the relationship between them was analysed. DI was calculated by the minimum velocity/maximum velocity of the HV waveform. An HVPG>12 mmHg was defined as severe portal hypertension. In a subgroup of 19 patients receiving propranolol, changes in both DI and HVPG were evaluated after propranolol administration for 3 months. One author (S. K. B.) performed all DI of Doppler HV waveform studies.</P><P>Results</P><P>Abnormal HV waveforms were seen in 66 of 76 patients (86.8%). DI significantly correlated with the grade of HVPG, i.e. with higher HVPG increased DI was observed (<I>P</I><0.01). By logistic regression analysis, DI>0.6 was significantly more likely to be severe portal hypertension (odds ratio: 14.19, 95% confidence interval: 4.07–49.55). Receiver-operating characteristic curve according to the value of 0.6 of DI showed a sensitivity of 75.9% and a specificity of 81.8% for the presence of severe portal hypertension. In 19 patients of the propranolol subgroup, change of DI following propranolol treatment also significantly correlated with that of HVPG (<I>P</I><0.01).</P><P>Conclusions</P><P>Damping index of the HV waveform by Doppler ultrasonography might be a non-invasive supplementary tool in evaluating the severity of portal hypertension and in responding to propranolol in patients with liver cirrhosis.</P>

Assessment of the integrity of human oocytes retrieved from cryopreserved ovarian tissue after xenotransplantation

Samuel Kim, S.,Kang, Hee Gyu,Kim, Nam Hyung,Lee, Hoi Chang,Lee, Hyang Heun Oxford University Press 2005 Human reproduction Vol.20 No.9

<P>BACKGROUND: Previous studies showed that immature oocytes stored in ovarian tissue could develop to the mature stage after transplantation. However, the quality and competency of the oocytes developed in xenografted ovarian tissue have never been investigated. As a pilot study to investigate this uncharted issue, we evaluated microtubule organization and chromatin configuration of human oocytes harvested from xenografted frozen–thawed ovarian tissue. METHODS: Frozen–thawed human ovarian tissue was transplanted into severe combined immunodeficient mice. All animals were stimulated with gonadotrophin from 20 weeks after transplantation. Grafts were recovered 36 h after hCG administration. The oocytes were retrieved from the antral follicles (>2 mm diameter), cultured <I>in vitro</I>, stained for microtubule and chromatin localization. RESULTS: Five oocytes from 21 female mice and seven oocytes from nine male mice were retrieved. Immunocytochemical examinations of these oocytes after <I>in vitro</I> maturation revealed only two developed to the metaphase II stage. Most oocytes were between prophase and metaphase with abnormal microtubule organization and chromatin configuration. CONCLUSIONS: Immature oocytes in stored human ovarian tissue can grow to maturity in host animals after xenotransplantation. Retrieval of oocytes from the xenograft can be carried out and is reproducible. However, many oocytes, grown in host animals and further matured <I>in vitro</I>, showed aberrant microtubule organization and chromatin patterns.</P>

Role of Heart in Refractory Ascites, Acute Kidney Injury and Hepatorenal Syndrome

( Samuel S. Lee ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Renal dysfunction is one of the dominant extrahepatic conditions invariably associated with the progression of cirrhosis. Theentire liver-kidney axis has been intensely studied over the past 5 decades but many questions remain unanswered to date.However, it is well known that as chronic liver disease progresses and worsens, it is accompanied by worsening renal function.In particular, the kidney behaves as if the body is severely volume-depleted, and thus intensely conserves salt and water. Theextent of such salt/water retention is mild in the early stages of compensated cirrhosis but gradually increases in rough correlationto increasing liver dysfunction and the onset of endstage decompensated cirrhosis. Thus as liver disease progresses, mild ascitesbecomes severe or refractory ascites, and the extreme end of the sodium/water retention spectrum can be seen: the conditionsof acute kidney injury (AKI) and hepatorenal syndrome (HRS) which are characterized by the most intense salt/water retentionof any human disease state, and the elaboration of small amounts of virtually sodium-free urine, or at its extreme, anuria.For the past half-century, the two theories to explain such renal dysfunction were the ‘underfill’ and the ‘overflow’ hypotheses.Over the past 3 decades, the ‘peripheral vasodilatation’ (PVD) hypothesis, which is actually a modest reworking of the ‘underfill’theory, has become the dominant, most widely-accepted theory. The PVD theory contends that the initiating event is widespreadperipheral vasodilatation is the initiating event that leads to an underfilled circulation, sensed by the kidney and other organsas ‘decreased effective circulating volume’. Thus the kidney conserves salt and water in a futile attempt to defend the circulation.The main factor responsible for the vasodilatation remains unsettled: nitric oxide excess has been suggested but note entirelysupported by experimental evidence. A general imbalance of the vasodilator:vasoconstrictor systems in favor of the former, hasgenerally been shown.Until our work on cirrhotic cardiomyopathy starting in 1990, all previous experimental studies in this topic had exclusively focusedon the peripheral vasculature in cirrhosis. However, just on first principles alone, it is clear that the pump at the center of theblood circulation must play a role in the genesis of a decreased effective circulation. In other words, whether or not the vesselsare dilated, in order for the circulation to be ineffective, pump function must also be abnormal in some way: either the vesselsare normal conduits and the pump is inadequate, or the vessels are dilated and pump function is inadequately compensatingfor the dilated conduits.This presentation will review clinical and experimental work over the past 2 decades that strongly suggests that inadequate pumpfunction, otherwise called cirrhotic cardiomyopathy, is a major contributor to the key concept of decreased effective circulatingvolume that lies at the heart* of the peripheral vasodilatation hypothesis. (* pun intended)

Albumin: New Roles beyond Volume Expander

( Samuel S. Lee ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Albumin is a 65-70kDa protein that accounts for approximately half the total plasma protein content in humans. For many years,it was thought that its only two functions were to bind to various substances so they could be transported or stabilized, andto provide a major part of the plasma oncotic pressure, also called colloid osmotic pressure.Research over the past 3 decades has established numerous other essential roles of albumin. Moreover, it has been found toimprove outcomes not just in liver disease but a number of other pathologic conditions including stroke, sepsis, acute lung injuryand subarachnoid hemorrhage. In liver disease, albumin has been found to be useful to help treat or manage spontaneous bacterialperitonitis, hepatorenal syndrome, resistant ascites, post-paracentesis circulatory dysfunction and hyponatremia.The other mechanisms of action besides its colloid osmotic effect can be grouped into several categories. These include substancedetoxification/stabilization, metal binding, cell stabilization and immune/anti-inflammatory effects. At the cellular level, it mediatesmany of these effects due to its small size, binding domains, charge and ability to enter a variety of cells. It thus subservesseveral important physiological functions in health, but in cirrhosis, several of these functions have been demonstrated to beimpaired.Specific examples of these normal beneficial cellular effects include reduction of oxidative stress and immune stabilizing. Albuminenters endothelial cells and in animal models of liver disease, has been shown to reduce the deleterious effects of LPS and endotoxinprimarily through a TLR-mediated effect. It also improves endothelial function as judged by markers such as Von WillebrandFactor production. It can also improve neutrophil function to reduce infection risk in cirrhosis. In the kidney, it appears to restorerenal blood flow autoregulation by an unclear mechanism. but one that seems to be largely independent of its effect as a volumeexpander. Several studies have demonstrated reduction of oxidative stress in the liver and vasculature by albumin.The function of numerous other organ systems in cirrhosis is known to be altered, and dysfunctional albumin may play rolesin those systems’ dysfunction.The role of albumin in the blood vessels and vasculature has been studied but possible effects in the cirrhotic lung and hearthave not yet been clarified. These areas are fertile ground for future research.

Quantitative assessment of ischemic injuries on primordial follicles and ovarian stromal cells in fresh and frozen-thawed ovarian tissue with a TUNEL method

김세웅 ( S. Samuel Kim ),( Hyun Won Yang ),( Dong Hoon Kim ),( Hoi Chang Lee ),( Hyang Heun Lee ),( Won Il Park ),( So Young Shin ) 대한산부인과학회 2002 대한산부인과학회 학술대회 Vol.88 No.-

Visibility analysis for the region of ICE-POP 2018: Yongpyong Alpine Centre

Samuel S. Park,Kwonil Kim,GyuWon Lee,Kwang-Deuk Ahn,SangWon Joo 한국기상학회 2016 한국기상학회 학술대회 논문집 Vol.2016 No.10

Mitochondrial-Targeted Catalase Protects Against High-Fat Diet–Induced Muscle Insulin Resistance by Decreasing Intramuscular Lipid Accumulation

Lee, Hui-Young,Lee, Jae Sung,Alves, Tiago,Ladiges, Warren,Rabinovitch, Peter S.,Jurczak, Michael J.,Choi, Cheol Soo,Shulman, Gerald I.,Samuel, Varman T. American Diabetes Association 2017 Diabetes Vol. No.

<P>We explored the role of reactive oxygen species (ROS) in the pathogenesis of muscle insulin resistance. We assessed insulin action in vivo with a hyperinsulinemic-euglycemic clamp in mice expressing a mitochondrial-targeted catalase (MCAT) that were fed regular chow (RC) or a high-fat diet (HFD) or underwent an acute infusion of a lipid emulsion. RC-fed MCAT mice were similar to littermate wild-type (WT) mice. However, HFD-fed MCAT mice were protected from diet-induced insulin resistance. In contrast, an acute lipid infusion caused muscle insulin resistance in both MCAT and WT mice. ROS production was decreased in both HFD-fed and lipid-infused MCAT mice and cannot explain the divergent response in insulin action. MCAT mice had subtly increased energy expenditure and muscle fat oxidation with decreased intramuscular diacylglycerol (DAG) accumulation, protein kinase C- (PKC) activation, and impaired insulin signaling with HFD. In contrast, the insulin resistance with the acute lipid infusion was associated with increased muscle DAG content in both WT and MCAT mice. These studies suggest that altering muscle mitochondrial ROS production does not directly alter the development of lipid-induced insulin resistance. However, the altered energy balance in HFD-fed MCAT mice protected them from DAG accumulation, PKC activation, and impaired muscle insulin signaling.</P>

Supersonic cold spraying of titania nanoparticles on reduced graphene oxide for lithium ion battery anodes

Samuel, Edmund,Lee, Jong-Gun,Joshi, Bhavana,Kim, Tae-Gun,Kim, Min-woo,Seong, Il Won,Yoon, Woo Young,Yoon, Sam S. ELSEVIER SCIENCE 2017 JOURNAL OF ALLOYS AND COMPOUNDS Vol.715 No.-

<P><B>Abstract</B></P> <P>Titania (TiO<SUB>2</SUB>) nanoparticles were uniformly distributed on and are well attached to reduced graphene oxide (rGO) by supersonic cold spraying. The process facilitated rapid production of lithium ion battery (LIB) anodes. Integration of TiO<SUB>2</SUB> with rGO not only enhanced the conductivity of the anode, but also prevented agglomeration of the titania nanoparticles, which facilitated uniform distribution of the nanoparticles and thus consistently reduced the electron diffusion length. Integration of rGO with TiO<SUB>2</SUB> widened the characteristic voltage range of the resulting rGO-TiO<SUB>2</SUB> composite (0.01–3 V) relative to that of pure TiO<SUB>2</SUB>, which enhanced the capacity during the lithiation process. Therefore, the LIB cell exhibited superior performance with long cycle durations even under high current rate. The optimal weight ratio of rGO to TiO<SUB>2</SUB> was found to be 1:1, which produced a retention capacity of 203 mA h g<SUP>−1</SUP> at <I>N</I> = 300 cycle under a current rate of 1 C = 336 mA g<SUP>−1</SUP>. Rapid production of rGO/TiO<SUB>2</SUB> nanocomposites via supersonic cold spraying may facilitate commercialization of high-quality LIB cells.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Uniform rGO-TiO<SUB>2</SUB> films were fabricated as LIB anode via rapid supersonic spraying. </LI> <LI> The optimized concentrations of rGO and TiO<SUB>2</SUB> presented to get higher capacity. </LI> <LI> Very high retention capacity of 203 mA h g<SUP>−1</SUP> is obtained at 1 C at 300th cycle. </LI> <LI> Excellent rate capability performance exhibited through synergy of rGO and TiO<SUB>2</SUB>. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated <i>RAG2</i> and accompanying severe combined immunodeficiency

Lee, Kiho,Kwon, Deug-Nam,Ezashi, Toshihiko,Choi, Yun-Jung,Park, Chankyu,Ericsson, Aaron C.,Brown, Alana N.,Samuel, Melissa S.,Park, Kwang-Wook,Walters, Eric M.,Kim, Dae Young,Kim, Jae-Hwan,Franklin, C National Academy of Sciences 2014 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.111 No.20

<P>Pigs with severe combined immunodeficiency (SCID) may provide useful models for regenerative medicine, xenotransplantation, and tumor development and will aid in developing therapies for human SCID patients. Using a reporter-guided transcription activator-like effector nuclease (TALEN) system, we generated targeted modifications of recombination activating gene (<I>RAG</I>) 2 in somatic cells at high efficiency, including some that affected both alleles. Somatic-cell nuclear transfer performed with the mutated cells produced pigs with <I>RAG2</I> mutations without integrated exogenous DNA. Biallelically modified pigs either lacked a thymus or had one that was underdeveloped. Their splenic white pulp lacked B and T cells. Under a conventional housing environment, the biallelic <I>RAG2</I> mutants manifested a “failure to thrive” phenotype, with signs of inflammation and apoptosis in the spleen compared with age-matched wild-type animals by the time they were 4 wk of age. Pigs raised in a clean environment were healthier and, following injection of human induced pluripotent stem cells (iPSCs), quickly developed mature teratomas representing all three germ layers. The pigs also tolerated grafts of allogeneic porcine trophoblast stem cells. These SCID pigs should have a variety of uses in transplantation biology.</P>

Conjugated Polyelectrolytes as Efficient Hole Transport Layers in Perovskite Light-Emitting Diodes

Lee, Bo Ram,Yu, Jae Choul,Park, Jong Hyun,Lee, Seungjin,Mai, Cheng-Kang,Zhao, Baodan,Wong, Matthew S.,Jung, Eui Dae,Nam, Yun Seok,Park, Song Yi,Di Nuzzo, Daniele,Kim, Jin Young,Stranks, Samuel D.,Baza American Chemical Society 2018 ACS NANO Vol.12 No.6

<P>Perovskite-based optoelectronic devices have been rapidly developing in the past 5 years. Since the first report, the external quantum efficiency (EQE) of perovskite light-emitting diodes (PeLEDs) has increased rapidly through the control of morphology and structure from 0.1% to more than 11%. Here, we report the use of various conjugated polyelectrolytes (CPEs) as the hole injection layer in PeLEDs. In particular, we find that poly[2,6-(4,4-bis-potassium butanylsulfonate)-4<I>H</I>-cyclopenta-[2,1-<I>b</I>;3,4-<I>b</I>′]-dithiophene)] (PCPDT-K) transfers holes effectively, blocks electron transport from the perovskite to the underlying ITO layer, and reduces luminescence quenching at the perovskite/PCPDT-K interface. Our optimized PeLEDs with PCPDT-K show enhanced EQE by a factor of approximately 4 compared to control PeLEDs with PEDOT:PSS, reaching EQE values of 5.66%, and exhibit improved device stability.</P> [FIG OMISSION]</BR>