bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Normal” Liver Stiffness Measure (LSM) Values Are Higher in Both Lean and Obese Individuals: A Population-Based Study From a Developing Country
Authors: Das Kausik , Sarkar Rajib , Ahmed Sk. Mahiuddin , Mridha Asit R. , Mukherjee Partha S. , Das Kshaunish , Dhali Gopal K. , Santra Amal , Chowdhury Abhijit 
Published: September 2011

Abstract

The liver stiffness measure (LSM) needs to be explored in ethnically and anthropometrically diverse healthy subjects (to derive an acceptable normal range) and also in patients with liver disease. In view of this objective, LSM was performed by transient elastography (TE) using FibroScan in 437 healthy subjects with normal alanine aminotransferase (ALT) levels, recruited from a free-living population of the Birbhum Population Project (BIRPOP;
www.shds.in
), a Health and Demographic Surveillance System (HDSS), and from 274 patients with liver disease attending the Hepatology Clinic of the School of Digestive and Liver Diseases (SDLD; Institute of Post Graduate Medical Education & Research [IPGME&R], Kolkata, India) including 188 with nonalcoholic fatty liver disease (NAFLD) and 86 with chronic hepatitis of viral and other etiologies. Liver biopsy was performed in 125 patients. The range of normal values for LSM, defined by 5th and 95th percentile values in healthy subjects, was 3.2 and 8.5 kPa, respectively. Healthy subjects with a lower body mass index (BMI; < <18.5 kg/m2) had a higher LSM compared with subjects who had a normal BMI; this LSM value was comparable to that of obese subjects (6.05 ± 1.78 versus 5.51 ± 1.59 and 6.60 ± 1.21,

P

= 0.016 and 0.349, respectively). Liver disease patients without histologic fibrosis had significantly higher LSM values compared with healthy subjects (7.52 ± 5.49 versus 5.63 ± 1.64,

P

< 0.001). Among the histologic variables, stage of fibrosis was the only predictor for LSM. LSM did not correlate with inflammatory activity and ALT in both NAFLD and chronic hepatitis groups.

Conclusion:

LSM varies between 3.2 and 8.5 kPa in healthy subjects of South Asian origin. Both lean and obese healthy subjects have higher LSM values compared with subjects with normal BMI. Liver stiffness begins to increase even before fibrosis appears in patients with liver disease. (Hepatology 2012)
Patients With Minimal Hepatic Encephalopathy Show Impaired Mismatch Negativity Correlating With Reduced Performance in Attention Tests
Authors: Felipo Vicente , Ordoño Juan F. , Urios Amparo , El Mlili Nisrin , Giménez-Garzó Carla , Aguado Carolina , González-Lopez Olga , Giner-Duran Remedios , Serra Miguel A. , Wassel Abdallah , Rodrigo Jose M. , Salazar José , Montoliu Carmina 
Published: September 2011

Abstract

Attention deficit is an early event in the cognitive impairment of patients with minimal hepatic encephalopathy (MHE). The underlying mechanisms remain unclear. Mismatch negativity (MMN) is an auditory event-related potential that reflects an attentional trigger. Patients with schizophrenia show impaired attention and cognitive function, which are reflected in altered MMN. We hypothesized that patients with MHE, similarly to those with schizophrenia, should show MMN alterations related with attention deficits. The aims of this work were to assess whether (1) MMN is altered in cirrhotic patients with MHE, compared to those without MHE, (2) MMN changes in parallel with performance in attention tests and/or MHE in a longitudinal study, and (3) MMN predicts performance in attention tests and/or in the Psychometric Hepatic Encephalopathy Score (PHES). We performed MMN analysis as well as attention and coordination tests in 34 control subjects and in 37 patients with liver cirrhosis without MHE and 23 with MHE. Patients with MHE show reduced performance in selective and sustained attention tests and in visuomotor and bimanual coordination tests. The MMN wave area was reduced in patients with MHE, but not in those without MHE. In the longitudinal study, MMN area improved in parallel with performance in attention tests and PHES in 4 patients and worsened in parallel in another 4. Logistic regression analyses showed that MMN area predicts performance in attention tests and in PHES, but not in other tests or critical flicker frequency. Receiver operating characteristic curve analyses showed that MMN area predicts attention deficits in the number connection tests A and B, Stroop tasks, and MHE, with sensitivities of 75%-90% and specificities of 76%-83%.

Conclusion :

MMN area is useful to diagnose attention deficits and MHE in patients with liver cirrhosis. (Hepatology 2012;)
Human Leukocyte Antigen Class II Molecules Confer Both Susceptibility and Progression in Japanese Patients With Primary Biliary Cirrhosis
Authors: Umemura Takeji , Joshita Satoru , Ichijo Tetsuya , Yoshizawa Kaname , Katsuyama Yoshihiko , Tanaka Eiji , Ota Masao 
Published: September 2011

Abstract

Along with twin and family studies, recent genome-wide association studies suggest that genetic factors contribute to the susceptibility and severity of primary biliary cirrhosis (PBC). Although several reports have demonstrated that the human leukocyte antigen (HLA)

DRB1*08:03

allele is associated with disease susceptibility in Japan, the precise analysis of HLA haplotypes and the role of amino acid alignment have not been fully clarified. We investigated HLA class I A, B, and C and HLA class II DRB1 and DQB1 alleles and haplotypes in 229 Japanese patients with PBC and compared them with the published data of 523 healthy subjects. Significant associations were found with PBC susceptibility for the

DRB1*08:03-DQB1*06:01

(13% versus 6%;

P

= 0.000025; odds ratio [OR] = 2.22) and

DRB1*04:05-DQB1*04:01

haplotypes (17% versus 13%;

P

= 0.044; OR = 1.38). Conversely, there were significant protective associations with the

DRB1*13:02-DQB1*06:04

(2% versus 5%;

P

= 0.00093; OR = 0.27) and

DRB1*11:01-DQB1*03:01

haplotypes (1% versus 4%;

P

= 0.03; OR = 0.37). The frequency of the

DRB1*09:01-DQB1*03:03

haplotype was significantly higher in patients who had received orthotopic liver transplantation (33% versus 11%;

P

= 0.0012; OR = 3.96). Furthermore, the frequency of serine at position 57 (

P

= 0.0000015; OR = 1.83) of the DRβchain differed the most in patients with PBC, compared with healthy subjects.

Conclusion :

This study established the role of HLA haplotypes in determining PBC susceptibility and progression in the Japanese population. Further resequencing of the HLA region is required to more precisely identify the genetic components of PBC. (Hepatology 2012)
Regulation of Hepatic Lipin-1 by Ethanol: Role of AMP-Activated Protein Kinase/Sterol Regulatory Element-Binding Protein 1 Signaling in Mice
Authors: Hu Ming , Wang Fengming , Li Xin , Rogers Christopher Q. , Liang Xiaomei , Finck Brian N. , Mitra Mayurranjan S. , Zhang Ray , Mitchell Dave A. , You Min 
Published: September 2011

Abstract

Lipin-1 is a protein that exhibits dual functions as a phosphatidic acid phosphohydrolase enzyme in the triglyceride synthesis pathways and a transcriptional coregulator. Our previous studies have shown that ethanol causes fatty liver by activation of sterol regulatory element-binding protein 1 (SREBP-1) and inhibition of hepatic AMP-activated protein kinase (AMPK) in mice. Here, we tested the hypothesis that AMPK-SREBP-1 signaling may be involved in ethanol-mediated up-regulation of lipin-1 gene expression. The effects of ethanol on lipin-1 were investigated in cultured hepatic cells and in the livers of chronic ethanol-fed mice. Ethanol exposure robustly induced activity of a mouse lipin-1 promoter, promoted cytoplasmic localization of lipin-1, and caused excess lipid accumulation, both in cultured hepatic cells and in mouse livers. Mechanistic studies showed that ethanol-mediated induction of lipin-1 gene expression was inhibited by a known activator of AMPK or overexpression of a constitutively active form of AMPK. Importantly, overexpression of the processed nuclear form of SREBP-1c abolished the ability of 5-aminoimidazole-4-carboxamide ribonucleoside to suppress ethanol-mediated induction of lipin-1 gene-expression level. Chromatin immunoprecipitation assays further revealed that ethanol exposure significantly increased the association of acetylated histone H3 at lysine 9 with the SRE-containing region in the promoter of the lipin-1 gene.

Conclusion:

In conclusion, ethanol-induced up-regulation of lipin-1 gene expression is mediated through inhibition of AMPK and activation of SREBP-1. (Hepatology 2012)
Translationally Controlled Tumor Protein Induces Mitotic Defects and Chromosome Missegregation in Hepatocellular Carcinoma Development
Authors: Chan Tim Hon Man , Chen Leilei , Liu Ming , Hu Liang , Zheng Bo-jian , Poon Vincent Kwok-Man , Huang Pinzhu , Yuan Yun-Fei , Huang Jian-dong , Yang Jie , Tsao George Sai-wah , Guan Xin-Yuan 
Published: September 2011

Abstract

Emerging evidence implicates the chromodomain helicase/ATPase DNA binding protein 1–like gene (

CHD1L

) as a specific oncogene in human hepatocellular carcinoma (HCC). To better understand the molecular mechanisms underlying HCC cases carrying

CHD1L

amplification (>50% HCCs), we identified a CHD1L target, translationally controlled tumor protein (

TCTP

), and investigated its role in HCC progression. Here, we report that CHD1L protein directly binds to the promoter region (nt −

733

to −

1,027

) of

TCTP

and activates

TCTP

transcription. Overexpression of TCTP was detected in 40.7% of human HCC samples analyzed and positively correlated with CHD1L overexpression. Clinically, overexpression of

TCTP

was significantly associated with the advanced tumor stage (

P

= 0.037) and overall survival time of HCC patients (

P

= 0.034). In multivariate analyses, TCTP was determined to be an independent marker associated with poor prognostic outcomes.

In vitro

and

in vivo

functional studies in mice showed that

TCTP

has tumorigenic abilities, and overexpression of

TCTP

induced by CHD1L contributed to the mitotic defects of tumor cells. Further mechanistic studies demonstrated that TCTP promoted the ubiquitin-proteasome degradation of Cdc25C during mitotic progression, which caused the failure in the dephosphorylation of Cdk1 on Tyr15 and decreased Cdk1 activity. As a consequence, the sudden drop of Cdk1 activity in mitosis induced a faster mitotic exit and chromosome missegregation, which led to chromosomal instability. The depletion experiment proved that the tumorigenicity of

TCTP

was linked to its role in mitotic defects.

Conclusion:

Collectively, we reveal a novel molecular pathway (CHD1L/TCTP/Cdc25C/Cdk1), which causes the malignant transformation of hepatocytes with the phenotypes of accelerated mitotic progression and the production of aneuploidy. (Hepatology 2012)
Hepatocellular Carcinoma Confirmation, Treatment, and Survival in Surveillance, Epidemiology, and End Results Registries, 1992-2008
Authors: Altekruse Sean F. , McGlynn Katherine A. , Dickie Lois A. , Kleiner David E. 
Published: September 2011

Abstract

Approaches to the diagnosis and management of hepatocellular carcinoma (HCC) are improving survival. In the Surveillance, Epidemiology, and End Results-13 registries, HCC stage, histological confirmation, and first-course surgery were examined. Among 21,390 HCC cases diagnosed with follow-up of vital status during 1998-2008, there were 4,727 (22%) with reported first-course invasive liver surgery, local tumor destruction, or both. The proportion with reported liver surgery or ablation was 39% among localized stage cases and only 4% among distant/unstaged cases. Though 70% of cases had histologically confirmed diagnoses, the proportion with confirmed diagnoses was higher among cases with reported invasive surgery (99%), compared to cases receiving ablation (81%) or no reported therapy (65%). Incidence rates of histologically unconfirmed HCC increased faster than those of confirmed HCC from 1992 to 2008 (8% versus 3% per year). Two encouraging findings were that incidence rates of localized-stage HCC increased faster than rates of regional- and distant-stage HCC combined (8% versus 4% per year), and that incidence rates of reported first-course surgery or tumor destruction increased faster than incidence rates of HCC without such therapy (11% versus 7%). Between 1975-1977 and 1998-2007, 5-year cause-specific HCC survival increased from just 3% to 18%. Survival was 84% among transplant recipients, 53% among cases receiving radiofrequency ablation at early stage, 47% among cases undergoing resection, and 35% among cases receiving local tumor destruction. Asian or Pacific Islander cases had significantly better 5-year survival (23%) than white (18%), Hispanic (15%), or black cases (12%).

Conclusion:

HCC survival is improving, because more cases are diagnosed and treated at early stages. Additional progress may be possible with continued use of clinical surveillance to follow individuals at risk for HCC, enabling early intervention. (Hepatology 2012;)
Mature Hepatocytes Exhibit Unexpected Plasticity by Direct Dedifferentiation Into Liver Progenitor Cells in Culture
Authors: Chen Yixin , Wong Philip P. , Sjeklocha Lucas , Steer Clifford J. , Sahin Behnan M. 
Published: September 2011

Abstract

Although there have been numerous reports describing the isolation of liver progenitor cells from the adult liver, their exact origin has not been clearly defined; and the role played by mature hepatocytes as direct contributors to the hepatic progenitor cell pool has remained largely unknown. Here, we report strong evidence that mature hepatocytes in culture have the capacity to dedifferentiate into a population of adult liver progenitors without genetic or epigenetic manipulations. By using highly purified mature hepatocytes, which were obtained from untreated, healthy rat liver and labeled with fluorescent dye PKH2, we found that hepatocytes in culture gave rise to a population of PKH2-positive liver progenitor cells. These cells, liver-derived progenitor cells, which share phenotypic similarities with oval cells, were previously reported to be capable of forming mature hepatocytes, both in culture and in animals. Studies done at various time points during the course of dedifferentiation cultures revealed that hepatocytes rapidly transformed into liver progenitors within 1 week through a transient oval cell-like stage. This finding was supported by lineage-tracing studies involving double-transgenic AlbuminCreXRosa26 mice expressing β-galactosidase exclusively in hepatocytes. Cultures set up with hepatocytes obtained from these mice resulted in the generation of β-galactosidase-positive liver progenitor cells, demonstrating that they were a direct dedifferentiation product of mature hepatocytes. Additionally, these progenitors differentiated into hepatocytes

in vivo

when transplanted into rats that had undergone retrorsine pretreatment and partial hepatectomy.

Conclusion :

Our studies provide strong evidence for the unexpected plasticity of mature hepatocytes to dedifferentiate into progenitor cells in culture, and this may potentially have a significant effect on the treatment of liver diseases requiring liver or hepatocyte transplantation. (Hepatology 2012;)
A Mouse Model of Accelerated Liver Aging Caused by a Defect in DNA Repair
Authors: Gregg Siobhán Q. , Gutiérrez Verónica , Rasile Robinson Andria , Woodell Tyler , Nakao Atsunori , Ross Mark A. , Michalopoulos George K. , Rigatti Lora , Rothermel Carrie E. , Kamileri Irene , Garinis George , Beer Stolz Donna , Niedernhofer Laura J. 
Published: September 2011

Abstract

The liver changes with age, leading to an impaired ability to respond to hepatic insults and increased incidence of liver disease in the elderly. Therefore, there is critical need for rapid model systems to study aging-related liver changes. One potential opportunity is murine models of human progerias or diseases of accelerated aging.

Ercc1

−/Δ mice model a rare human progeroid syndrome caused by inherited defects in DNA repair. To determine whether hepatic changes that occur with normal aging occur prematurely in

Ercc1

−/Δ mice, we systematically compared liver from 5-month-old progeroid

Ercc1

−/Δ mice to old (24-36-month-old) wild-type (WT) mice. Both displayed areas of necrosis, foci of hepatocellular degeneration, and acute inflammation. Loss of hepatic architecture, fibrosis, steatosis, pseudocapillarization, and anisokaryosis were more dramatic in

Ercc1

−/Δ mice than in old WT mice. Liver enzymes were significantly elevated in serum of

Ercc1

−/Δ mice and old WT mice, whereas albumin was reduced, demonstrating liver damage and dysfunction. The regenerative capacity of

Ercc1

−/Δ liver after partial hepatectomy was significantly reduced. There was evidence of increased oxidative damage in

Ercc1

−/Δ and old WT liver, including lipofuscin, lipid hydroperoxides and acrolein, as well as increased hepatocellular senescence. There was a highly significant correlation in genome-wide transcriptional changes between old WT and 16-month-old, but not 5-week-old,

Ercc1

−/Δ mice, emphasizing that the

Ercc1

−/Δ mice acquire an aging profile in early adulthood.

Conclusion:

There are strong functional, regulatory, and histopathological parallels between accelerated aging driven by a DNA repair defect and normal aging. This supports a role for DNA damage in driving aging and validates a murine model for rapidly testing hypotheses about causes and treatment for aging-related hepatic changes. (Hepatology 2012)
Electrophysiological indices of altered working memory processes in long‐term ecstasy users
Authors: Nulsen Claire , Fox Allison , Hammond Geoff 
Published: September 2011

ObjectiveThe aim of this study was to determine the effect of light long‐term ecstasy consumption on verbal short‐term and working memory and to identify the cognitive processes contributing to task performance.MethodElectroencephalogram was recorded while ecstasy users (N = 11), polydrug users (N = 13), and non‐users (N = 13) completed forward and backward serial recognition tasks designed to engage verbal short‐term memory and verbal working memory, respectively.ResultsAll three groups displayed significantly lower digit‐backward span than digit‐forward span with ecstasy users displaying the greatest difference. The parietally distributed P3b was significantly smaller in the digits backward task than in the digits forward task in non‐ecstasy‐using controls. Ecstasy users did not show the reduced P3b component in the backward task that was seen in both non‐ecstasy‐using control groups.ConclusionsEcstasy users' performance was suppressed more by the concurrent processing demands of the working memory task than that of the non‐ecstasy‐using controls. Non‐ecstasy‐using controls showed differential event‐related potential wave forms in the short‐term and working memory tasks, and this pattern was not seen in the ecstasy users. This is consistent with a reduction in the cognitive resources allocated to processing in working memory in ecstasy users. Copyright © 2011 John Wiley & Sons, Ltd.
Expression of ER stress and autophagy‐related molecules in human non‐small cell lung cancer and premalignant lesions
Authors: Kim Kyoung Min , Yu Tack Keun , Chu Hyun Hee , Park Ho Sung , Jang Kyu Yun , Moon Woo Sung , Kang Myoung Jae , Lee Dong Geun , Kim Min Ho , Lee Ju Hyung , Chung Myoung Ja 
Published: September 2011

AbstractStress that impairs endoplasmic reticulum (ER) function leads to an accumulation of unfolded or misfolded proteins in the ER (ER stress). Autophagy is a lysosomal pathway involved in the turnover of cellular macromolecules and organelles, which emerging data indicate that ER stress is also a potent inducer of autophagy. ER stress and autophagy are involved in human cancer. We examined the expression of ER stress‐related proteins [GRP78 and C/EBP homologous protein (CHOP)] and autophagic proteins (Beclin‐1 and LC3) in non‐small cell lung carcinomas (NSCLCs), bronchioloalveolar carcinomas (BACs) and atypical adenomatous hyperplasias (AAHs) to understand their role in the NSCLC pathogenesis. The expression of GRP78 and CHOP, Beclin‐1 and LC3 were analyzed using immunohistochemistry on tissue sections from 133 NSCLC (69 squamous cell carcinomas, 56 adenocarcinomas (AC) and eight other NSCLCs), 21 BAC and 9 AAH. Expression of GRP78 and Beclin‐1 was correlated with low tumor stage (p < 0.001 and p = 0.019, respectively) and longer survival (p = 0.007 and p <0.001, respectively) by Kaplan–Meier analysis. However, CHOP was correlated with high tumor stage (p = 0.038) and shorter survival (p = 0.012). Expression of GRP78 and Beclin‐1 was positively correlated (p = 0.006). Our study showed that the expression of GRP78, CHOP, Beclin‐1 and LC3 in lung cancer and its relation with clinicopathologic factors and patients survival. These results suggest that GRP78, CHOP and Beclin‐1 may play an important role in tumorigenesis of lung AC and may serve as new prognostic indicators for outcome of the patients with NSCLC.
Raman spectroscopy for the non‐contact and non‐destructive monitoring of collagen damage within tissues
Authors: Votteler Miriam , Carvajal Berrio Daniel A. , Pudlas Marieke , Walles Heike , Stock Ulrich A. , Schenke‐Layland Katja 
Published: September 2011

AbstractThe non‐destructive and label‐free monitoring of extracellular matrix (ECM) remodeling and degradation processes is a great challenge. Raman spectroscopy is a non‐contact method that offers the possibility to analyze ECM in situ without the need for tissue processing. Here, we employed Raman spectroscopy for the detection of heart valve ECM, focusing on collagen fibers. We screened the leaflets of porcine aortic valves either directly after dissection or after treatment with collagenase. By comparing the fingerprint region of the Raman spectra of control and treated tissues (400–1800 cm–1), we detected no significant differences based on Raman shifts; however, we found that increasing collagen degradation translated into decreasing Raman signal intensities. After these proof‐of‐principal experiments, we compared Raman spectra of native and cryopreserved valve tissues and revealed that the signal intensities of the frozen samples were significantly lower compared to those of native tissues, similar to the data seen in the enzymatically‐degraded tissues. In conclusion, our data demonstrate that Raman microscopy is a promising, non‐destructive and non‐contact tool to probe ECM state in situ. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Interplay between long‐ and short‐range interactions drives neuritogenesis on stiff surfaces
Authors: Lamour Guillaume , Souès Sylvie , Hamraoui Ahmed 
Published: September 2011

AbstractSubstrate factors such as surface energy distribution can affect cell functions, such as neuronal differentiation of PC12 cells. However, the surface effects that trigger such cell responses need to be clarified and analyzed. Here we show that the total surface tension is not a critical parameter. Self‐assembled monolayers of alkylsiloxanes on glass were used as culture substrates. By changing the nanoscale structure and ordering of the monolayer, we designed surfaces with a range of dispersive (γd) and nondispersive (γnd) potentials, but with a similar value for total free‐energy (50 ≤ γd+ γnd≤ 55 mNm−1). When seeded on surfaces displaying γd/γnd≤ 3.7, PC12 cells underwent low level of neuritogenesis. On surfaces exhibiting γd/γnd≥ 5.4, neurite outgrowth was greatly enhanced and apparent by only 24 h of culture in absence of nerve growth‐factor treatment. These data indicate how the spatial distribution of surface potentials may control neuritogenesis, thus providing a new criterion to address nerve regeneration issues on rigid biocompatible surfaces. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.