Serial computed tomography and its uses in the diagnosis of pathological changes in the liver, pancreas and kidneys

International Nuclear Information System (INIS)

Schmiedel, R.

1983-01-01

The investigations described were carried out in such a way as to fulfil the defined requirements of serial computed tomography like short periods of measurement, high scanning frequency and intravasal bolus injection of a contrast medium that would readily be excreted by the renal route. In this connection, the following questions were of particular interest: 1. Is computed serial tomography able to provide better clues to tissue identification and the distinction between normal and pathological structures in the liver, pancreas and kidneys? 2. Would it be possible to obtain information as to the degree of vascularisation in space-occupying pathological processes in the liver, pancreas and kidneys? 3. Is serial computed tomography a useful tool to diagnose specific pathological changes in the liver, pancreas and kidneys? 4. Would this investigation permit predictions to be made about the functional performance of the liver, pancreas and kidneys? (orig./MG) [de

Non-invasive measurement of liver and pancreas fibrosis in patients with cystic fibrosis.

Science.gov (United States)

Friedrich-Rust, Mireen; Schlueter, Nina; Smaczny, Christina; Eickmeier, Olaf; Rosewich, Martin; Feifel, Kirstin; Herrmann, Eva; Poynard, Thierry; Gleiber, Wolfgang; Lais, Christoph; Zielen, Stefan; Wagner, Thomas O F; Zeuzem, Stefan; Bojunga, Joerg

2013-09-01

Patients with cystic fibrosis (CF) have a relevant morbidity and mortality caused by CF-related liver-disease. While transient elastography (TE) is an established elastography method in hepatology centers, Acoustic-Radiation-Force-Impulse (ARFI)-Imaging is a novel ultrasound-based elastography method which is integrated in a conventional ultrasound-system. The aim of the present study was to evaluate the prevalence of liver-fibrosis in patients with CF using TE, ARFI-imaging and fibrosis blood tests. 106 patients with CF were prospectively included in the present study and received ARFI-imaging of the left and right liver-lobe, ARFI of the pancreas TE of the liver and laboratory evaluation. The prevalence of liver-fibrosis according to recently published best practice guidelines for CFLD was 22.6%. Prevalence of significant liver-fibrosis assessed by TE, ARFI-right-liver-lobe, ARFI-left-liver-lobe, Fibrotest, Fibrotest-corrected-by-haptoglobin was 17%, 24%, 40%, 7%, and 16%, respectively. The best agreement was found for TE, ARFI-right-liver-lobe and Fibrotest-corrected-by-haptoglobin. Patients with pancreatic-insufficiency had significantly lower pancreas-ARFI-values as compared to patients without. ARFI-imaging and TE seem to be promising non-invasive methods for detection of liver-fibrosis in patients with CF. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Abdominal MR: liver and pancreas

International Nuclear Information System (INIS)

Bartolozzi, C.; Lencioni, R.; Donati, F.; Cioni, D.

1999-01-01

Following the introduction of rapid, high-quality scan techniques and the development of new, tissue-specific contrast agents, the applications of MRI for abdominal imaging are experiencing unprecedented growth. This article examines the current status of liver and pancreatic MRI, highlighting technical and methodological approach, use of contrast agents, and main clinical applications. The MRI technique appears to be the ideal diagnostic tool for detection and characterization of benign and malignant liver neoplasms, and for evaluating tumor response after nonsurgical treatments. Dynamic imaging after bolus injection of a gadolinium chelate is currently a fundamental component of an MRI examination of the liver in many instances. Optimal dynamic scanning depends on the use of a multisection spoiled gradient-echo technique that allows one to image the entire region of interest during a single suspended respiration. Images are obtained during four phases relative to the injection of the contrast agent: precontrast, arterial (pre-sinusoidal), portal (sinusoidal), and delayed (extracellular) phase. Liver-specific contrast agents, including hepatobiliary agents and reticuloendothelial system-targeted iron oxide particles, however, may offer advantages over gadolinium chelates in some clinical settings. Computed tomography is still preferred to MRI for imaging the pancreas. However, state-of-the-art MRI may currently be at least as accurate as spiral CT for depiction of inflammatory and neoplastic pancreatic diseases. Moreover, MRI has the advantage of allowing simultaneous investigation of the biliary tree, owing to cholangiopancreatography techniques. Hence, a comprehensive assessment of most pancreatic diseases can be achieved with a single examination. (orig.)

Altered morphology of liver and pancreas tissues of offsprings of ...

African Journals Online (AJOL)

The relationship between consumption of charred meat, which is believed to be rich in nitrosamine by pregnant mothers and the adverse effects on the growth of their offsprings, alterations in morphology of tissues like liver and pancreas were studied. Meat was subjected to charcoal fire roasting without curing and was ...

Synthesis and biological evaluation of [11C]AZ12504948; a novel tracer for imaging of glucokinase in pancreas and liver

International Nuclear Information System (INIS)

Jahan, M.; Johnström, P.; Nag, S.; Takano, A.; Korsgren, O.; Johansson, L.; Halldin, C.; Eriksson, O.

2015-01-01

Introduction: Glucokinase (GK) is potentially a target for imaging of islets of Langerhans. Here we report the radiosynthesis and preclinical evaluation of the GK activator, [ 11 C]AZ12504948, for in vivo imaging of GK. Methods: [ 11 C]AZ12504948 was synthesized by O-methylation of the precursor, AZ125555620, using carbon-11 methyl iodide ([ 11 C]CH 3 I). Preclinical evaluation was performed by autoradiography (ARG) of human tissues and PET/CT studies in pig and non-human primate. Result: [ 11 C]AZ12504948 was produced in reproducible good radiochemical yield in 28–30 min. Radiochemical purity of the formulated product was > 98% for up to 2 h with specific radioactivities 855 ± 209 GBq/μmol (n = 8). The preclinical evaluation showed some specificity for GK in liver, but not in pancreas. Conclusion: [ 11 C]AZ12504948 images GK in liver, but the low specificity impedes the visualization of GK in pancreas. Improved target specificity is required for further progress using PET probes based on this class of GK activators

The role of 3-D imaging and computer-based postprocessing for surgery of the liver and pancreas

International Nuclear Information System (INIS)

Grenacher, L.; Kauffmann, G.W.; Richter, G.M.; Thorn, M.; Vetter, M.; Hassenpflug, P.; Meinzer, H.P.; Knaebel, H.P.; Kraus, T.; Buechler, M.W.

2005-01-01

Cross-sectional imaging based on navigation and virtual reality planning tools are well-established in the surgical routine in orthopedic surgery and neurosurgery. In various procedures, they have achieved a significant clinical relevance and efficacy and have enhanced the discipline's resection capabilities. In abdominal surgery, however, these tools have gained little attraction so far. Even with the advantage of fast and high resolution cross-sectional liver and pancreas imaging, it remains unclear whether 3D planning and interactive planning tools might increase precision and safety of liver and pancreas surgery. The inability to simply transfer the methodology from orthopedic or neurosurgery is mainly a result of intraoperative organ movements and shifting and corresponding technical difficulties in the on-line applicability of presurgical cross sectional imaging data. For the interactive planning of liver surgery, three systems partly exist in daily routine: HepaVision2 (MeVis GmbH, Bremen), LiverLive (Navidez Ltd. Slovenia) and OrgaNicer (German Cancer Research Center, Heidelberg). All these systems have realized a half- or full-automatic liver-segmentation procedure to visualize liver segments, vessel trees, resected volumes or critical residual organ volumes, either for preoperative planning or intraoperative visualization. Acquisition of data is mainly based on computed tomography. Three-dimensional navigation for intraoperative surgical guidance with ultrasound is part of the clinical testing. There are only few reports about the transfer of the visualization of the pancreas, probably caused by the difficulties with the segmentation routine due to inflammation or organ-exceeding tumor growth. With this paper, we like to evaluate and demonstrate the present status of software planning tools and pathways for future pre- and intraoperative resection planning in liver and pancreas surgery. (orig.)

Impact of Post-Discharge Disposition on Risk and Causes of Readmission Following Liver and Pancreas Surgery.

Science.gov (United States)

Chen, Qinyu; Merath, Katiuscha; Olsen, Griffin; Bagante, Fabio; Idrees, Jay J; Akgul, Ozgur; Cloyd, Jordan; Schmidt, Carl; Dillhoff, Mary; Beal, Eliza W; White, Susan; Pawlik, Timothy M

2018-03-22

The relationship between the post-discharge settings and the risk of readmission has not been well examined. We sought to identify the association between discharge destinations and readmission rates after liver and pancreas surgery. The 2013-2015 Medicare-Provider Analysis and Review (MEDPAR) database was reviewed to identify liver and pancreas surgical patients. Patients were subdivided into three groups based on discharge destination: home/self-care (HSC), home with home health assistance (HHA), and skilled nursing facility (SNF). The association between post-acute settings, readmission rates, and readmission causes was assessed. Among 15,141 liver or pancreas surgical patients, 60% (n = 9046) were HSC, 26.9% (n = 4071) were HHA, and 13.4% (n = 2024) were SNF. Older, female patients and patients with ≥ 2 comorbidities, ≥ 2 previous admissions, an emergent index admission, an index complication, and ≥ 5-day length of stay were more likely to be discharged to HHA or SNF compared to HSC (all P readmission, respectively. The HHA and SNF settings were also associated with a 33 and a 69% higher risk of 90-day readmission. There was no association between discharge destination and readmission causes. Among liver and pancreas surgical patients, HHA and SNF patients had a higher risk of readmission within 30 and 90 days. There was no difference in readmission causes and discharge settings. The association between discharge setting and the higher risk of readmission should be further evaluated as the healthcare system seeks to reduce readmission rates after surgery.

Auxiliary en-bloc liver-small bowel transplantation with partial pancreas preservation in pigs

Institute of Scientific and Technical Information of China (English)

Zhen-Yu Yin; Xiao-Dong Ni; Feng Jiang; Ning Li; You-Sheng Li; Xiao-Ming Wang; Jie-Shou Li

2004-01-01

AIM: The aim of this study was to describe an auxiliary combined liver-small bowel transplantation model with the preservation of duodenum, head of pancreas and hepatic biliary system in pigs. The technique, feasibility, security and immunosuppression were commented.METHODS: Forty outbred long-white pigs were randomized into two groups, and the auxiliary composite liver/small bowel allotransplantations were undertaken in 10 long-white pigs in each group with the recipient liver preserved.Group A was not treated with immunosuppressive drugs while group B was treated with cyclosporine A and methylprednisolone after operation. The hemodynamic changes and amylase of body fluid (including blood, urine and abdominal drain) were analyzed.RESULTS: The average survival time of the animals was 10±1.929 d (6 to 25 d) in group A while more than 30 d in group B. The pigs could tolerate the hemodynamic fluctuation during operation and the hemodynamic parameters recovered to normal 2 h after blood reperfusion. The transient high amylase level was decreased to normal one week after operation and autopsy showed no pancreatitis.CONCLUSION: Auxiliary en-bloc liver-small bowel transplantation with partial pancreas preservation is a feasible and safe model with simplified surgical techniques for composite liver/small bowel transplantation. This model may be used as a preclinical training model for clinical transplantation method, clinical liver-small bowel transplantation related complication research, basic research including immunosuppressive treatment, organ preservation, acute rejection, chronic rejection, immuno-tolerance and xenotransplantation.

Neurofunctional imaging of the pancreas utilizing the cholinergic PET radioligand [18F]4-fluorobenzyltrozamicol

International Nuclear Information System (INIS)

Clark, P.B.; Gage, H.D.; Brown-Proctor, C.; Buchheimer, N.; Morton, K.A.; Calles-Escandon, J.; Mach, R.H.

2004-01-01

The pancreas is one of the most heavily innervated peripheral organs in the body. Parasympathetic and sympathetic neurons terminate in the pancreas and provide tight control of endocrine and exocrine functions. The aim of this study was to determine whether the pancreas can be imaged with a radioligand that binds to specific neuroreceptors. Using fluorine-18 4-fluorobenzyltrozamicol (FBT), which binds to the presynaptic vesicular acetylcholine transporter, positron emission tomography scans were performed in four adult mice, two adult rhesus monkeys, and one adult human. In these mammals, the pancreas is intensely FBT avid, with uptake greater than in any other organ at 30, 60, and 90 min. The maximum standardized uptake value (SUV) ratios of pancreas to liver, for example, ranged from 1.4 to 1.7 in rhesus monkeys (mean 1.6; median 1.7) and from 1.9 to 4.7 (mean 3.24; median 3.02) in mice. The maximum SUV ratio of pancreas to liver in the human was 1.8. These data suggest that neuroreceptor imaging of the pancreas in vivo is feasible in animal models and humans. This imaging could allow researchers to interrogate functions under control of the autonomic nervous system in the pancreas, with applications possible in transplanted and native pancreata. Also, as beta cell function is intimately related to parasympathetic cholinergic input, FBT activity in the pancreas may correlate with insulin-producing beta cell mass. This could ultimately provide a method of in vivo imaging in animal models and humans for diabetes research. (orig.)

YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population

DEFF Research Database (Denmark)

Kjaergaard, Alisa D; Bojesen, Stig E; Nordestgaard, Børge G

2014-01-01

BACKGROUND: We tested the hypothesis that observationally and genetically increased YKL-40 concentrations are associated with alcoholic liver and pancreas damage and disease. METHODS: We performed cohort and mendelian randomization in 86,258 individuals from the Danish general population......, with measured concentrations of plasma YKL-40 (n = 21 646) and CHI3L1 rs4950928 genotype (n = 84 738). RESULTS: Increased YKL-40 was associated with increased alanine aminotransferase, bilirubin, alkaline phosphatase, γ-glutamyl transferase, erythrocyte mean corpuscular volume, C-reactive protein...... alcoholic liver disease, 4.1 (1.7-10) for alcoholic pancreatitis, and 3.4 (1.9-6.1) for any pancreatitis. CHI3L1 rs4950928 genotype explained 14% of the variation in plasma YKL-40 concentrations but was not associated with alcoholic liver and pancreas damage or disease. A doubling in YKL-40 concentrations...

Positron Scanning of Liver and Pancreas; Exploration de Foie et du Pancreas par les Positrons; Pozitronoskopiya pecheni i podzheludochnoj zhelezy; Exploracion del higado y del pancreas mediante positrones

Energy Technology Data Exchange (ETDEWEB)

Aronow, S; Thors, R; Brownell, G L [Physics Research Laboratory and Department of Surgery, Massachusetts General Hospital, Boston, MA (United States)

1959-07-01

The success of the positron scanning technique in the localization of brain tumors has suggested its application to other organs. Zinc-62 is used in an attempt to delineate the pancreas and copper-64 in various forms is used to delineate the liver. The problem of visualizing the pancreas is particularly difficult because of its small size and the presence of large organs in the vicinity which concentrate zinc. Several approaches to this problem are discussed. Copper-64 in simple ionic form and in the form of copper versenate concentrate to a marked degree in the liver. Positron scans of the liver would seem to offer considerable promise for successful 'diagnosis of various liver disorders. Data is presented on the distribution of several isotopes and compounds in animals. (author) [French] Devant le succes avec lequel la technique de detection par les positrons a ete utilisee pour la localisation des tumeurs du cerveau, on a ete amene a l'appliquer a d'autres organes. On s'est servi de zinc-62 pour tenter de determiner le contour du pancreas, et de cuivre-64, sous diverses formes, pour le contour du foie. Il est particulieremen t difficile de rendre visible le pancreas en raison de sa petite taille et de la presence d'organes voisins de grandes dimensions, qui concentrent le zinc. Les auteurs etudient plusieurs procedes par lesquels on s'est efforce de resoudre ce probleme. Le cuivre-64 sous forme ionique simple et sous forme de sel de l'acide ethylene-diamino-tetra-acetique se ooncentre fortement dans le foie. L'exploration du foie a l'aide des positrons parait devoir faciliter considerablemen t le diagnostic de differents troubles hepatiques. Les auteurs donnent des indications sur la repartition de plusieurs isotopes et composes chez des animaux. (author) [Spanish] El exito de la tecnica de exploracion mediante positrones en la localization de tumores cerebrales aconseja su aplicacion a otros organos. El zinc-62 y el cobre-64 en diferentes formas se utilizan

Paediatric ultrasonography of the liver, hepatobiliary tract and pancreas

Energy Technology Data Exchange (ETDEWEB)

Rijn, R.R. van, E-mail: r.r.vanrijn@amc.uva.nl [Department of Radiology, Emma Children' s Hospital – Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Nievelstein, R.A.J. [Department of Radiology, Wilhelmina Children' s Hospital – University Medical Center, Heidelberglaan 100, 3584 CX Utrecht (Netherlands)

2014-09-15

In the field of paediatric radiology ultrasonography (US) is the most versatile imaging tool available. Children in general, by virtue of their body composition, are excellent candidates for US exams in whom abdominal anatomy and pathology can be visualised in great detail. The fact that during the US study a clinical history can be obtained strongly adds to the value of the US exam. This does require investment in time and expertise and ideally a paediatric radiologist performing the exam. In this review the role of ultrasonography (US) of the liver, biliary tract and pancreas in children is discussed.

Liver, bone marrow, pancreas and pituitary gland iron overload in young and adult thalassemic patients: a T2 relaxometry study

International Nuclear Information System (INIS)

Argyropoulou, Maria I.; Astrakas, Loukas; Metafratzi, Zafiria; Efremidis, Stavros C.; Kiortsis, Dimitrios N.; Chalissos, Nikolaos

2007-01-01

Thirty-seven patients with β-thalassemia major, including 14 adolescents (15.2 ± 3.0 years) and 23 adults (26.4 ± 6.9 years), were studied. T2 relaxation time (T2) of the liver, bone marrow, pancreas and pituitary gland was measured in a 1.5-Tesla magnetic resonance (MR) imager, using a multiecho spin-echo sequence (TR/TE 2,000/20, 40, 60, 80, 100, 120, 140, 160 ms). Pituitary gland height was evaluated in a midline sagittal scan of a spin-echo sequence (TR/TE, 500/20 ms). The T2 of the pituitary gland was higher in adolescents (59.4 ± 15 ms) than in adults (45.3 ± 10.4 ms), P < 0.05. The T2 of the pancreas was lower in adolescents (43.6 ± 10.3 ms) than in adults (54.4 ± 10.4 ms). No difference among groups was found in the T2 of the liver and bone marrow. There was no significant correlation of the T2 among the liver, pancreas, pituitary gland and bone marrow. There was no significant correlation between serum ferritin and T2 of the liver, pancreas and bone marrow. Pituitary T2 showed a significant correlation with pituitary gland height (adolescents: R = 0.63, adults: R = 0.62, P < 0.05) and serum ferritin (adolescents: R = -0.60, adults: R = -0.50, P < 0.05). In conclusion, iron overload evaluated by T2 is organ specific. After adolescence, age-related T2 changes are predominantly associated with pituitary siderosis and fatty degeneration of the pancreas. Pituitary size decreases with progressing siderosis. (orig.)

Liver, bone marrow, pancreas and pituitary gland iron overload in young and adult thalassemic patients: a T2 relaxometry study

Energy Technology Data Exchange (ETDEWEB)

Argyropoulou, Maria I.; Astrakas, Loukas; Metafratzi, Zafiria; Efremidis, Stavros C. [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Kiortsis, Dimitrios N. [University of Ioannina, Laboratory of Physiology, Medical School, Ioannina (Greece); Chalissos, Nikolaos [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); University of Ioannina, Laboratory of Physiology, Medical School, Ioannina (Greece)

2007-12-15

Thirty-seven patients with {beta}-thalassemia major, including 14 adolescents (15.2 {+-} 3.0 years) and 23 adults (26.4 {+-} 6.9 years), were studied. T2 relaxation time (T2) of the liver, bone marrow, pancreas and pituitary gland was measured in a 1.5-Tesla magnetic resonance (MR) imager, using a multiecho spin-echo sequence (TR/TE 2,000/20, 40, 60, 80, 100, 120, 140, 160 ms). Pituitary gland height was evaluated in a midline sagittal scan of a spin-echo sequence (TR/TE, 500/20 ms). The T2 of the pituitary gland was higher in adolescents (59.4 {+-} 15 ms) than in adults (45.3 {+-} 10.4 ms), P < 0.05. The T2 of the pancreas was lower in adolescents (43.6 {+-} 10.3 ms) than in adults (54.4 {+-} 10.4 ms). No difference among groups was found in the T2 of the liver and bone marrow. There was no significant correlation of the T2 among the liver, pancreas, pituitary gland and bone marrow. There was no significant correlation between serum ferritin and T2 of the liver, pancreas and bone marrow. Pituitary T2 showed a significant correlation with pituitary gland height (adolescents: R = 0.63, adults: R = 0.62, P < 0.05) and serum ferritin (adolescents: R = -0.60, adults: R = -0.50, P < 0.05). In conclusion, iron overload evaluated by T2 is organ specific. After adolescence, age-related T2 changes are predominantly associated with pituitary siderosis and fatty degeneration of the pancreas. Pituitary size decreases with progressing siderosis. (orig.)

Chrysin treatment improves diabetes and its complications in liver, brain, and pancreas in streptozotocin-induced diabetic rats.

Science.gov (United States)

Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Samini, Fariborz; Farkhondeh, Tahereh

2016-04-01

Chrysin (CH) is a natural flavonoid with pharmacological influences. The purpose of the current study was the assessment of possible protective effects of CH against oxidative damage in the serum, liver, brain, and pancreas of streptozotocin (STZ)- induced diabetic rats. In the present study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, 3 CH (20, 40, 80 mg/kg/day)-treated diabetic groups. To find out the modulations of cellular antioxidant defense systems, malondialdehyde (MDA) level and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in the serum, liver, brain, and pancreas. STZ caused an elevation of glucose, MDA, TG, TC, LDL-C and with reduction of HDL-C, total protein, SOD, CAT, and GST in the serum, liver, brain, and pancreas (p < 0.01). The findings showed that the significant elevation in the glucose, MDA, TG, TC, LDL-C and reduction of HDL-C, total protein, SOD, CAT, and GST were ameliorated in the CH-treated diabetic groups versus to the untreated groups, in a dose dependent manner (p < 0.05). The current study offers that CH may be recovered diabetes and its complications by modification of oxidative stress.

The Human Pancreas Proteome Defined by Transcriptomics and Antibody-Based Profiling

Science.gov (United States)

Fagerberg, Linn; Hallström, Björn M.; Schwenk, Jochen M.; Uhlén, Mathias; Korsgren, Olle; Lindskog, Cecilia

2014-01-01

The pancreas is composed of both exocrine glands and intermingled endocrine cells to execute its diverse functions, including enzyme production for digestion of nutrients and hormone secretion for regulation of blood glucose levels. To define the molecular constituents with elevated expression in the human pancreas, we employed a genome-wide RNA sequencing analysis of the human transcriptome to identify genes with elevated expression in the human pancreas. This quantitative transcriptomics data was combined with immunohistochemistry-based protein profiling to allow mapping of the corresponding proteins to different compartments and specific cell types within the pancreas down to the single cell level. Analysis of whole pancreas identified 146 genes with elevated expression levels, of which 47 revealed a particular higher expression as compared to the other analyzed tissue types, thus termed pancreas enriched. Extended analysis of in vitro isolated endocrine islets identified an additional set of 42 genes with elevated expression in these specialized cells. Although only 0.7% of all genes showed an elevated expression level in the pancreas, this fraction of transcripts, in most cases encoding secreted proteins, constituted 68% of the total mRNA in pancreas. This demonstrates the extreme specialization of the pancreas for production of secreted proteins. Among the elevated expression profiles, several previously not described proteins were identified, both in endocrine cells (CFC1, FAM159B, RBPJL and RGS9) and exocrine glandular cells (AQP12A, DPEP1, GATM and ERP27). In summary, we provide a global analysis of the pancreas transcriptome and proteome with a comprehensive list of genes and proteins with elevated expression in pancreas. This list represents an important starting point for further studies of the molecular repertoire of pancreatic cells and their relation to disease states or treatment effects. PMID:25546435

Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing Cells

Directory of Open Access Journals (Sweden)

Irit Meivar-Levy

2011-01-01

Full Text Available Activation of the pancreatic lineage in the liver has been suggested as a potential autologous cell replacement therapy for diabetic patients. Transcription factors-induced liver-to-pancreas reprogramming has been demonstrated in numerous species both in vivo and in vitro. However, human-derived liver cells capable of acquiring the alternate pancreatic repertoire have never been characterized. It is yet unknown whether hepatic-like stem cells or rather adult liver cells give rise to insulin-producing cells. Using an in vitro experimental system, we demonstrate that proliferating adherent human liver cells acquire mesenchymal-like characteristics and a considerable level of cellular plasticity. However, using a lineage-tracing approach, we demonstrate that insulin-producing cells are primarily generated in cells enriched for adult hepatic markers that coexpress both albumin and mesenchymal markers. Taken together, our data suggest that adult human hepatic tissue retains a substantial level of developmental plasticity, which could be exploited in regenerative medicine approaches.

Irradiation with X-rays phase-advances the molecular clockwork in liver, adrenal gland and pancreas.

Science.gov (United States)

Müller, Mareike Hildegard; Rödel, Franz; Rüb, Udo; Korf, Horst-Werner

2015-02-01

The circadian clock of man and mammals shows a hierarchic organization. The master clock, located in the suprachiasmatic nuclei (SCN), controls peripheral oscillators distributed throughout the body. Rhythm generation depends on molecular clockworks based on transcriptional/translational interaction of clock genes. Numerous studies have shown that the clockwork in peripheral oscillators is capable to maintain circadian rhythms for several cycles in vitro, i.e. in the absence of signals from the SCN. The aim of the present study is to analyze the effects of irradiation with X-rays on the clockwork of liver, adrenal and pancreas. To this end organotypic slice cultures of liver (OLSC) and organotypic explant cultures of adrenal glands (OAEC) and pancreas (OPEC) were prepared from transgenic mPer2(luc) mice which express luciferase under the control of the promoter of an important clock gene, Per2, and allow to study the dynamics of the molecular clockwork by bioluminometry. The preparations were cultured in a membrane-based liquid-air interface culturing system and irradiated with X-rays at doses of 10 Gy and 50 Gy or left untreated. Bioluminometric real-time recordings show a stable oscillation of all OLSC, OAEC and OPEC for up to 12 days in vitro. Oscillations persist after irradiation with X-rays. However, a dose of 50 Gy caused a phase advance in the rhythm of the OLSC by 5 h, in the OPEC by 7 h and in the OAEC by 6 h. Our study shows that X-rays affect the molecular clockwork in liver, pancreas and adrenal leading to phase advances. Our results confirm and extend previous studies showing a phase-advancing effect of X-rays at the level of the whole animal and single cells.

SU-F-T-636: Comprehensive Approach to Motion Assessment for Liver and Pancreas SBRT Patients

Energy Technology Data Exchange (ETDEWEB)

Halvorsen, P; Iftimia, I; Hunter, K [Lahey Hospital and Medical Center, Burlington, MA (United States)

2016-06-15

Purpose: Our past practice for liver and pancreas SBRT consisted of free breathing (FB) with gated treatment delivery using a 30-70% phase window. We have recently adopted an assessment method leading to individualized motion management to minimize target motion. We present our results from 47 patients treated with this new approach. Methods: We perform an initial patient coaching and assessment session in our conventional simulator suite to observe the motion of the implanted fiducials with FB anterior and lateral 20-second cine acquisitions. The physician decides whether to attempt inhale or exhale breath-hold (BH). The patient is coached while observing with cine to ascertain their ability to achieve the desired BH mode for long periods as needed for treatment delivery. If the patient cannot comply, a FB approach is adopted using gating or simple ITV method (for patients without fiducials). After achieving a patient-specific motion management mode, we perform CT-simulation using the Varian RPM system to reproduce the chosen mode and record a reference session for treatment delivery. For pre-treatment imaging, the fiducials are observed under fluoro while coaching the patient. Results: Of 47 SBRT cases analyzed, 32 were liver and 15 were pancreas. The chosen techniques were: 32 exhale BH (12 with abdominal compression), 7 FB gated, 4 inhale BH, and 4 FB ITV. Maximum fiducial motion amplitude was 5 mm for the FB gated patients, and less than 5 mm for all BH patients with most able to achieve a maximum amplitude of 3 mm. Conclusion: This study showed that an individualized motion management approach can reduce the target volume and, therefore, the volume of irradiated healthy tissue from liver or pancreas SBRT. Effective coaching is essential in achieving consistent BH with 3 mm amplitude. The fluoro/cine session is helpful in establishing the right coaching approach for each patient.

SU-F-T-636: Comprehensive Approach to Motion Assessment for Liver and Pancreas SBRT Patients

International Nuclear Information System (INIS)

Halvorsen, P; Iftimia, I; Hunter, K

2016-01-01

Purpose: Our past practice for liver and pancreas SBRT consisted of free breathing (FB) with gated treatment delivery using a 30-70% phase window. We have recently adopted an assessment method leading to individualized motion management to minimize target motion. We present our results from 47 patients treated with this new approach. Methods: We perform an initial patient coaching and assessment session in our conventional simulator suite to observe the motion of the implanted fiducials with FB anterior and lateral 20-second cine acquisitions. The physician decides whether to attempt inhale or exhale breath-hold (BH). The patient is coached while observing with cine to ascertain their ability to achieve the desired BH mode for long periods as needed for treatment delivery. If the patient cannot comply, a FB approach is adopted using gating or simple ITV method (for patients without fiducials). After achieving a patient-specific motion management mode, we perform CT-simulation using the Varian RPM system to reproduce the chosen mode and record a reference session for treatment delivery. For pre-treatment imaging, the fiducials are observed under fluoro while coaching the patient. Results: Of 47 SBRT cases analyzed, 32 were liver and 15 were pancreas. The chosen techniques were: 32 exhale BH (12 with abdominal compression), 7 FB gated, 4 inhale BH, and 4 FB ITV. Maximum fiducial motion amplitude was 5 mm for the FB gated patients, and less than 5 mm for all BH patients with most able to achieve a maximum amplitude of 3 mm. Conclusion: This study showed that an individualized motion management approach can reduce the target volume and, therefore, the volume of irradiated healthy tissue from liver or pancreas SBRT. Effective coaching is essential in achieving consistent BH with 3 mm amplitude. The fluoro/cine session is helpful in establishing the right coaching approach for each patient.

Internal radiotherapy of liver cancer with rat hepato-carcinoma-intestine-pancreas gene as a liver tumor-specific promoter

Energy Technology Data Exchange (ETDEWEB)

Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J. [Hop Paul Brousse, INSERM, Hepatobiliary Ctr, U785, F-94800 Villejuif (France); Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J. [Univ Paris Sud, Fac Med, F-94800 Villejuif (France); Boisgard, R.; Tavitian, B. [INSERM, U803, F-91400 Orsay (France); Boisgard, R.; Tavitian, B. [CEA, Serv Hosp Frederic Joliot, Lab Imagerie Mol Expt, F-91400 Orsay (France); Roux, J.; Cales, P. [Univ Angers, UPRES EA 3859, Lab Hemodynam Interact Fibrose et Invas Tumorale H, Angers (France); Clerc, J. [Hop Cochin, AP HP, Dept Nucl Med, F-75014 Paris (France)

2008-07-01

The hepato-carcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg III {alpha}, is activated in most human hepatocellular carcinomas (HCCs) but not in normal liver, which suggests that HIP regulatory sequence could be used as efficient liver tumor-specific promoters to express a therapeutic polynucleotide in liver cancer. The sodium iodide sym-porter (NIS), which has recognized therapeutic and reporter gene properties, is appropriate to evaluate the transcriptional strength and specificity of the HIP promoter in HCC. For this purpose, we constructed a recombinant rat HIP-NIS adeno-viral vector (AdrHIP-NIS), and evaluated its performance as a mediator of selective radio-iodide uptake in tumor hepatocytes. Western blot, immunofluorescence, and iodide uptake assays were performed in AdrHIP-NIS-infected primary hepatocytes and transformed hepatic and non-hepatic cells. Nuclear imaging, tissue counting and immuno-histo-chemistry were performed in normal and HCC-bearing Wistar rats infected with AdrHIP-NIS intra-tumorally or via the hepatic artery. In AdrHIP-NIS-infected transformed hepatic cells, functional NIS was strongly expressed, as in cells infected with a cytomegalovirus-NIS vector. No NIS expression was found in AdrHIP-NIS-infected normal hepatocytes or transformed non-hepatic cells. In rats bearing multi-nodular HCC, AdrHIP-NIS triggered functional NIS expression that was preferential in tumor hepatocytes. Administration of 18 mCi of {sup 131}I resulted in the destruction of AdrHIP-NIS-injected nodules. This study has identified the rHIP regulatory sequence as a potent liver tumor-specific promoter for the transfer of therapeutic genes, and AdrHIP-NIS-mediated. {sup 131}I therapy as a valuable option for the treatment of multi-nodular HCC. (authors)

Internal radiotherapy of liver cancer with rat hepato-carcinoma-intestine-pancreas gene as a liver tumor-specific promoter

International Nuclear Information System (INIS)

Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J.; Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J.; Boisgard, R.; Tavitian, B.; Boisgard, R.; Tavitian, B.; Roux, J.; Cales, P.; Clerc, J.

2008-01-01

The hepato-carcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg III α, is activated in most human hepatocellular carcinomas (HCCs) but not in normal liver, which suggests that HIP regulatory sequence could be used as efficient liver tumor-specific promoters to express a therapeutic polynucleotide in liver cancer. The sodium iodide sym-porter (NIS), which has recognized therapeutic and reporter gene properties, is appropriate to evaluate the transcriptional strength and specificity of the HIP promoter in HCC. For this purpose, we constructed a recombinant rat HIP-NIS adeno-viral vector (AdrHIP-NIS), and evaluated its performance as a mediator of selective radio-iodide uptake in tumor hepatocytes. Western blot, immunofluorescence, and iodide uptake assays were performed in AdrHIP-NIS-infected primary hepatocytes and transformed hepatic and non-hepatic cells. Nuclear imaging, tissue counting and immuno-histo-chemistry were performed in normal and HCC-bearing Wistar rats infected with AdrHIP-NIS intra-tumorally or via the hepatic artery. In AdrHIP-NIS-infected transformed hepatic cells, functional NIS was strongly expressed, as in cells infected with a cytomegalovirus-NIS vector. No NIS expression was found in AdrHIP-NIS-infected normal hepatocytes or transformed non-hepatic cells. In rats bearing multi-nodular HCC, AdrHIP-NIS triggered functional NIS expression that was preferential in tumor hepatocytes. Administration of 18 mCi of 131 I resulted in the destruction of AdrHIP-NIS-injected nodules. This study has identified the rHIP regulatory sequence as a potent liver tumor-specific promoter for the transfer of therapeutic genes, and AdrHIP-NIS-mediated. 131 I therapy as a valuable option for the treatment of multi-nodular HCC. (authors)

Autoradiography of manganese: accumulation and retention in the pancreas

International Nuclear Information System (INIS)

Lyden, A.; Lindquist, N.G.; Larsson, B.S.

1983-01-01

By means of whole-body autoradiography, the general distribution of 54 MnCl 2 was studied in mice and a Marmoset monkey. High accumulation and retention were observed in the pancreas in both species. Gamma counting experiments in mice after a single intravenous injection of 54 MnCl 2 showed that the level in the pancreas exceeded that of the liver at all survival times (20 min. - 30 days). Also in the monkey, the concentration in the pancreas exceeded that of the liver, and the pancreas had the highest tissue/liver ratio of the organs measured at 24 hours after injection. The high uptake and long retention in the pancreas suggest that manganese is of importance for the pancreatic function but also that the pancreas may be a target organ for manganese toxicity. Positron tomography, using 11 C-labelled amino acids, has been found to be a promising diagnostic technique for the study of pancreatic disease. Positron emitting manganese isotopes may be worth further studies as possible agents for pancreatic imaging. (author)

Anti-soluble liver antigen/liver-pancreas (SLA/LP) antibodies in pediatric patients with autoimmune hepatitis.

Science.gov (United States)

Vitozzi, Susana; Djilali-Saiah, Idriss; Lapierre, Pascal; Alvarez, Fernando

2002-12-01

Antibodies against soluble liver antigen/liver-pancreas (SLA/LP) have been associated with severe autoimmune hepatitis (AIH) and poor outcome, but most of these reports have focused on adult patients. The aim of this study was to assess the prevalence and clinical significance of anti-SLA/LP antibodies in a pediatric population with AIH. We developed a quantitative enzyme-linked immunoassay (ELISA), a Western blot (WB) and an immunoprecipitation assay (IPA) based on recombinant cDNA from activated Jurkat cells. The specificity of these tests was validated by testing 200 serum samples from healthy subjects, and from patients with liver and non-liver diseases. Anti-SLA/LP antibodies were found in patients with type 1 and type 2 AIH. The prevalence of these antibodies in patients with type 1 AIH was: 42% when tested by ELISA, 15% by WB and 50% by IPA. In patients with type 2 AIH, the prevalence rates were 42% by ELISA, 18% by WB and 44% by IPA. The mean titer values for anti-SLA/LP antibodies was significantly higher in type 2 AIH (1:1,300 +/- 339) than in type 1 AIH (1:600 +/- 71; p LKM1) and anti-liver cytosol type 1 (LC1) antibodies in sera. The presence of anti-SLA/LP showed a significant female preponderance in type 1 and 2 AIH patients (p = 0.0003 and p = 0.003, respectively), and was significantly correlated with a lower age at diagnosis (p = 0.05) in type 1 AIH patients. In conclusion, anti-SLA/LP antibodies in pediatric patients are associated with both type 1 and 2 AIH.

Proglucagon processing in porcine and human pancreas

DEFF Research Database (Denmark)

Holst, J J; Bersani, M; Johnsen, A H

1994-01-01

In the pancreas proglucagon (PG), a peptide precursor of 160 amino acids is cleaved to produce glucagon and a 30-amino acid N-terminal flanking peptide, but the fate of the C-terminal flanking peptide (99 amino acids) is incompletely known. We subjected acid ethanol extracts of human and porcine...... pancreases to gel filtration and analyzed the fractions with specific radioimmunoassays for the following regions of proglucagon: PG 62-69, PG 72-81, PG 78-87, PG 98-107 amide, PG 126-134, and PG 149-158. Based on these assays and successive purifications by high performance liquid chromatography we isolated...... PG 72-158 = 9971) was isolated from human pancreas together with small amounts of a peptide corresponding to PG 72-107 amide. Thus, the pancreatic processing of the C-terminal flanking peptide in proglucagon includes the formation of equimolar (to glucagon) amounts of PG 64-69 and PG 72-158 (major...

Computed tomography of the pancreas

International Nuclear Information System (INIS)

Kolmannskog, F.; Kolbenstvedt, A.; Aakhus, T.; Bergan, A.; Fausa, O.; Elgjo, K.

1980-01-01

The findings by computed tomography in 203 cases of suspected pancreatic tumours, pancreatitis or peripancreatic abnormalities were evaluated. The appearances of the normal and the diseased pancreas are described. Computed tomography is highly accurate in detecting pancreatic masses, but can not differentiate neoplastic from inflammatory disease. The only reliable signs of pancreatic carcinoma are a focal mass in the pancreas, together with liver metastasis. When a pancreatic mass is revealed by computed tomography, CT-guided fine-needle aspiration biopsy of the pancreas is recommended. Thus the need for more invasive diagnostic procedures and explorative laparotomy may be avoided in some patients. (Auth.)

From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

Science.gov (United States)

Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

2005-05-01

Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

The influence of liver and pancreas surgery on the thyroid function

Directory of Open Access Journals (Sweden)

Wojciechowska-Durczynska Katarzyna

2012-12-01

Full Text Available Abstract Background Nowadays, the increasing number of oncologic patients with liver or pancreatic tumours are subjected to surgical treatment, as it can provide a long-term survival or sometimes cure. As a result, numerous new clinical questions regarding metabolic disturbances in these patients have been arisen. Among others, the impact of the pancreas and liver surgery extent in relation to the thyroid function remains to be elucidated. Materials and methods The study comprised 51 patients (25 men and 26 women, mean age ± SD 61.6 ± 10.4 yrs, mean ± SD with pancreatic or liver tumours, qualified for abdominal operation. Serum levels of FT3, FT4 and TSH were measured on the day before (time “0” and on the 1st, 3rd and 5th day after surgery in two (2 subgroups reflecting the extent of surgery: twenty seven (27 patients (14 men and 13 women, mean age ± SD 61.5 ± 11.8 yrs after major surgery (Whipple’s surgery, right and left hemihepatectomy, segmentectomy of the liver, distal pancreatectomy, total duodenopancreatectomy and twenty four (24 patients (11 men and 13 women, mean age ± SD 61.8 ± 8.9 yrs after minor, palliative surgery (exploratory laparotomy, gastroenterostomy, triple by-pass, liver tumour embolization, hepaticojejunostomy. Additionally, the obtained results were analyzed in relation to the type of the disease (pancreatic surgery vs liver surgery. Results Mean serum FT3 level decreased significantly during the study in major and minor surgery subgroups (prd and 5th day after major surgery was lower in pancreatic tumour patients in comparison to liver tumour patients (p=0.002, p=0.032, respectively. Similarly, mean FT3 concentration on the 3rd day in minor surgery subgroup was lower in pancreatic tumour patients in comparison to liver tumour patients (p=0.015. Discussion Our findings have confirmed essential reduction of FT3 values after abdominal surgery, independently of surgery extent. Additionally, pancreatic tumour

Laparoscopic removal of a needle from the pancreas

Directory of Open Access Journals (Sweden)

Amit Jain

2013-01-01

Full Text Available Foreign bodies inside the pancreas are rare and usually occur after the ingestion of sharp objects like fish bone, sewing needle and toothpick. Most of the ingested foreign bodies pass spontaneously through the anus without being noticed but about 1% of them can perforate through the wall of stomach or duodenum to reach solid organs like pancreas or liver. Once inside the pancreas they can produce complications like abscess, pseudoaneurysm or pancreatits. Foreign bodies of pancreas should be removed by endoscopic or surgical methods. We hereby report our experience of successful removal one a sewing needle from pancreas.

[Adiponectin in patients with metabolic syndrome and diseases of the liver, bile ducts and pancreas].

Science.gov (United States)

Vašura, Adam; Blaho, Martin; Dítě, Petr; Kupka, Tomáš; Svoboda, Pavel; Martínek, Arnošt

Epidemiological data show that the metabolic syndrome can be diagnosed in up to 30 % of the population. Regarding 5 components of the metabolic syndrome, three of them, in case of positivity (visceral obesity, arterial hypertension, hypertriglyceridemia, changes of HDL-cholesterol levels and type 2 diabetes mellitus), are pathogenic factors which are the most frequently related to cardiovascular diseases, but currently they are also the focus of interest for gastroenterologists. The relationship between non-alcoholic hepatic steatosis, including non-alcoholic steatohepatitis, has been described. Less is known so far about the relation to the pancreas disease, particularly with respect to the status referred to as non-alcoholic fatty pancreas disease. The hormone selectively produced by adipose tissue is adiponectin. This protein is studied as a possible biomarker in people with metabolic syndrome, including obesity. Besides that, there is a question studied whether adiponectin can also play a significant role in the pathogenesis of diseases associated with fat building up in parenchymatous organs. Finding a reliable biomarker for patients with metabolic syndrome or diseases of the liver, biliary system and pancreas in relation to metabolic syndrome, presents a big challenge. And adiponectin is one of the promising biomarkers.Key words: adiponectin - biliary disease - metabolic syndrome - pancreatic steatosis - steatohepatitis.

Tributyltin chloride leads to adiposity and impairs metabolic functions in the rat liver and pancreas.

Science.gov (United States)

Bertuloso, Bruno D; Podratz, Priscila L; Merlo, Eduardo; de Araújo, Julia F P; Lima, Leandro C F; de Miguel, Emilio C; de Souza, Leticia N; Gava, Agata L; de Oliveira, Miriane; Miranda-Alves, Leandro; Carneiro, Maria T W D; Nogueira, Celia R; Graceli, Jones B

2015-05-19

Tributyltin chloride (TBT) is an environmental contaminant used in antifouling paints of boats. Endocrine disruptor effects of TBT are well established in animal models. However, the adverse effects on metabolism are less well understood. The toxicity of TBT in the white adipose tissue (WAT), liver and pancreas of female rats were assessed. Animals were divided into control and TBT (0.1 μg/kg/day) groups. TBT induced an increase in the body weight of the rats by the 15th day of oral exposure. The weight gain was associated with high parametrial (PR) and retroperitoneal (RP) WAT weights. TBT-treatment increased the adiposity, inflammation and expression of ERα and PPARγ proteins in both RP and PR WAT. In 3T3-L1 cells, estrogen treatment reduced lipid droplets accumulation, however increased the ERα protein expression. In contrast, TBT-treatment increased the lipid accumulation and reduced the ERα expression. WAT metabolic changes led to hepatic inflammation, lipid accumulation, increase of PPARγ and reduction of ERα protein expression. Accordingly, there were increases in the glucose tolerance and insulin sensitivity tests with increases in the number of pancreatic islets and insulin levels. These findings suggest that TBT leads to adiposity in WAT specifically, impairing the metabolic functions of the liver and pancreas. Copyright © 2015. Published by Elsevier Ireland Ltd.

Pancreas preservation for pancreas and islet transplantation

Science.gov (United States)

Iwanaga, Yasuhiro; Sutherland, David E.R.; Harmon, James V.; Papas, Klearchos K.

2010-01-01

Purpose of review To summarize advances and limitations in pancreas procurement and preservation for pancreas and islet transplantation, and review advances in islet protection and preservation. Recent findings Pancreases procured after cardiac death, with in-situ regional organ cooling, have been successfully used for islet transplantation. Colloid-free Celsior and histidine-tryptophan-ketoglutarate preservation solutions are comparable to University of Wisconsin solution when used for cold storage before pancreas transplantation. Colloid-free preservation solutions are inferior to University of Wisconsin solution for pancreas preservation prior to islet isolation and transplantation. Clinical reports on pancreas and islet transplants suggest that the two-layer method may not offer significant benefits over cold storage with the University of Wisconsin solution: improved oxygenation may depend on the graft size; benefits in experimental models may not translate to human organs. Improvements in islet yield and quality occurred from pancreases treated with inhibitors of stress-induced apoptosis during procurement, storage, isolation or culture. Pancreas perfusion may be desirable before islet isolation and transplantation and may improve islet yields and quality. Methods for real-time, noninvasive assessment of pancreas quality during preservation have been implemented and objective islet potency assays have been developed and validated. These innovations should contribute to objective evaluation and establishment of improved pancreas preservation and islet isolation strategies. Summary Cold storage may be adequate for preservation before pancreas transplants, but insufficient when pancreases are processed for islets or when expanded donors are used. Supplementation of cold storage solutions with cytoprotective agents and perfusion may improve pancreas and islet transplant outcomes. PMID:18685343

Ontogeny of neuro-insular complexes and islets innervation in the human pancreas.

Directory of Open Access Journals (Sweden)

Alexandra E. Proshchina

2014-04-01

Full Text Available The ontogeny of the neuro-insular complexes (NIC and the islets innervation in human pancreas has not been studied in detail. Our aim was to describe the developmental dynamics and distribution of the nervous system structures in the endocrine part of human pancreas. We used doublestaining with antibodies specific to pan-neural markers (neuron-specific enolase (NSE and S100 protein and to hormones of pancreatic endocrine cells. NSE and S100-positive nerves and ganglia were identified in the human fetal pancreas from gestation week (gw 10 onwards. Later the density of S100 and NSE-positive fibers increased. In adults this network was sparse. The islets innervation started to form from gw 14. NSE-containing endocrine cells were identified from gw 12 onwards. Additionally, S100-positive cells were detected both in the periphery and within some of the islets starting at gw 14. The analysis of islets innervation has shown that the fetal pancreas contained neuro-insular complexes and the number of these complexes was reduced in adults. The highest density of neuro-insular complexes is detected during middle and late fetal periods, when the mosaic islets, typical for adults, form. The close integration between the developing pancreatic islets and the nervous system structures may play an important role not only in the hormone secretion, but also in the islets morphogenesis.

Ontogeny of neuro-insular complexes and islets innervation in the human pancreas.

Science.gov (United States)

Proshchina, Alexandra E; Krivova, Yulia S; Barabanov, Valeriy M; Saveliev, Sergey V

2014-01-01

The ontogeny of the neuro-insular complexes (NIC) and the islets innervation in human pancreas has not been studied in detail. Our aim was to describe the developmental dynamics and distribution of the nervous system structures in the endocrine part of human pancreas. We used double-staining with antibodies specific to pan-neural markers [neuron-specific enolase (NSE) and S100 protein] and to hormones of pancreatic endocrine cells. NSE and S100-positive nerves and ganglia were identified in the human fetal pancreas from gestation week (gw) 10 onward. Later the density of S100 and NSE-positive fibers increased. In adults, this network was sparse. The islets innervation started to form from gw 14. NSE-containing endocrine cells were identified from gw 12 onward. Additionally, S100-positive cells were detected both in the periphery and within some of the islets starting at gw 14. The analysis of islets innervation has shown that the fetal pancreas contained NIC and the number of these complexes was reduced in adults. The highest density of NIC is detected during middle and late fetal periods, when the mosaic islets, typical for adults, form. The close integration between the developing pancreatic islets and the nervous system structures may play an important role not only in the hormone secretion, but also in the islets morphogenesis.

Inhibition of warm ischemic injury to rat liver, pancreas, and heart grafts by controlling the nutritional status of both donor and recipient.

Science.gov (United States)

Nishihara, V; Sumimoto, R; Fukuda, Y; Southard, J H; Asahara, T; Dohi, K

1997-01-01

In this study, we tested the effect of donor fasting with or without the use of an essential fatty acids deficiency (EFAD) diet in the recipient using rat heart, pancreas, and liver transplant models. We then compared the survivals, tumor necrosis factor alpha (TNF-alpha) response, and white cell accumulation in rats in order to clarify the mechanisms of the beneficial effect of donor fasting and recipient EFAD. It was found that when the grafts were obtained from fasted donors and then transplanted into fed recipients, the survival rate was significantly higher for all three grafts than for those obtained from fed rats and transplanted into fed rats. The best survival was seen for pancreas grafts obtained from fasted donors and then transplanted into EFAD recipients. TNF-alpha secretion was significantly suppressed in both fasted and EFAD rats, and both the total cell count and neutrophil count were suppressed in EFAD rats. These results clearly indicate that in addition to liver grafts, both heart and pancreas grafts obtained from fasted animals are more tolerant to warm ischemic injury. Furthermore, the combination of donor fasting and recipient EFAD acts synergistically to inhibit the post-transplantation inflammatory reaction (through decreased TNF-alpha secretion and white cell accumulation), thus resulting in an improved survival.

Simultaneous Kidney-Pancreas Transplantation With an Original "Transverse Pancreas" Technique: Initial 9 Years' Experience With 56 Cases.

Science.gov (United States)

Paulino, J; Martins, A; Vigia, E; Marcelino, P; Nobre, A M; Bicho, L; Filipe, E; Barroso, E

2017-10-01

An innovative technique for pancreas transplantation is described. The main aspect consists of the horizontal positioning of the pancreas, which allows a better venous outflow, thus preventing thrombosis and graft loss. The program of pancreas transplantation in this national reference center for pancreatic and liver surgery was started in 2007; the initial results were considered poor, resulting in the loss of half of the grafts due to venous thrombosis. After analyzing the possible causes, this technique was proposed and successfully implemented, reducing the postoperative complications, particularly the problem of venous thrombosis. A detailed description of the new surgical technique is provided. The main clinical and demographic characteristics of the 56 patients who underwent the surgery are analyzed. The incidence of venous thrombosis was 5.3% (3 patients) and graft loss was 3.5% (2 patients). Due to the good results, this technique became the standard surgery for transplantation of the pancreas in our center. The technique proved to be safe and successful. Due to the unique pancreas graft implantation, we called it "transverse pancreas surgery." Copyright © 2017 Elsevier Inc. All rights reserved.

Method of pancreas scintigraphy

International Nuclear Information System (INIS)

Michele, E.; Schmidt, H.A.E.

1976-01-01

Scintigraphy of the pancreas is important because of a lack of simple internal and x-ray pancreas diagnostic examination methods, non-burdening to the patient, yet providing sufficient evidence. We conceived a double isotope subtraction method aimed at widespread application; financially, it should be within the range even of smaller nuclear medicine departments. A scanner is combined with double impulse processing and a subtraction unit (Picker Dualscanner) and an adapted x-ray unit with the x-ray tube aimed at the scan-field. Commercial sup(Se-75)selenium methionine is used for pancreas imagining. sup(TC-99m)colloidal sulphur is used as a liver indicator. After barium-brei application orally, an x-ray is taken of the gastro-intestinal tract, so as to be able to delineate the pancreas from other epigastric organs also able to accumulate methionine. The subtraction photoscan is then inscribed on this pre-exposed film without any shift of the patient. It is also possible to use two parallel films (x-ray/photoscan) and then to superposition them

Normal Uptake of 11C-Acetate in Pancreas, Liver, Spleen, and Suprarenal Gland in PET

Directory of Open Access Journals (Sweden)

Bogdan Malkowski

2017-01-01

Full Text Available Purpose. C11-Acetate is radiotracer being considered an alternative to 18F-fluorodeoxyglucose. Evaluation of C11-acetate biodistribution in human parenchymal organs is described. Methods and Materials. 60 consecutive patients referred to C11-acetate PET CT suspected of renal or prostate cancer relapse with negative results (no recurrent tumor were included in the study. Acquisition from the base of skull to upper thigh was made 20 min after i.v. injection of 720 MBq of C11-acetate. The distribution was evaluated by measuring the uptake in pancreas (uncinate process and body separately, liver, spleen, and left suprarenal gland. Clinical data of included patients showed no abnormalities in these organs. Results. Biodistributions of C11-acetate radiotracer were compared in different organs. Standardized uptake values of 11C-acetate were significantly higher in pancreatic parenchyma (SUV mean 6,4 than in liver (SUV mean 3,3, spleen (SUV mean 4,5, or suprarenal gland (SUV mean 2,7 tissues. No significant difference was found between pancreatic head (SUV mean 6,4 and body (SUV mean 5,9 uptake. In case of all aforementioned organs, there were no differences either between both sexes or between formerly diagnosed tumors (renal and prostate. Conclusions. Evaluation of C11-acetate uptake differences in parenchymal organs will allow establishing normal patterns of distribution. High pancreatic uptake may be used in quantitative assessment of organ function in diffuse nonneoplastic pathology.

Does human pancreas contain salivary-type isoamylase?

Science.gov (United States)

Shimamura, J; Fridhandler, L; Berk, J E

1975-01-01

Amylase isoenzyme analysis was made of extracts of normal human pancreatic tissue by first conducting ion exchange chromatography of the purified material. This gave evidence of only pancreatic type (P-type) isoamylase for all purposes. However, when effluent fractions in which salivary type isoamylase would ordinarily be expected to be present were harvested, pooled, concentrated, and rechromatographed, the pancreatic extracts were found to contain some salivary type (S-type) isoamylase. The latter accounted for approximately 0-8 to 1-7% of the total recovered amylase activity. This finding of S-type isoamylase in normal human pancreas potentially has important bearing on the interpretation of isamylase analysis. PMID:1218813

The pancreas from Aristotle to Galen.

Science.gov (United States)

Tsuchiya, Ryoichi; Kuroki, Tamotsu; Eguchi, Susumu

2015-01-01

The first description of the pancreas in literature is found in Aristotle's Historia Animalium, but it is modified by "so-called". Therefore, the origin is pursued more extensively. The Greek-English Lexicon recommends three treatises as a possible original source. These three and Galen's other papers are investigated. In 2005, Sachs et al. suggested an origin of the pancreas might have derived from the intestinal divination using the avian pancreas. This report is evaluated. The avian pancreas which is the intraperitoneal organ, might have been well known by the intestinal divination, and people have called the organ pankreas or kallikreas. Anatomical dissection on human body was not accepted before the Aristotle's time. "So-called pancreas" in Historia must have been interpolated by Theophrastus. He was the most faithful and reliable disciple of Aristotle and succeeded the Aristotle's school. He and Macedonian ruler of Egypt Ptolemy I had known each other and there had been a strong link between them. The contemporary Herophilus performed many public dissections on both human and animal bodies in Alexandria. He named the various parts of the human body and designated the beginning intestine as duodenum. Yet in his extant works, the pancreas is not found. It is surmised that Herophilus may be the first to recognize the human pancreas, which is fixed with retroperitoneal tissue, and he named it "so-called pancreas". Theophrastus might have interpolated Herophilus' designation in Historia Animalium. Galen also uses "so-called pancreas" to designate the human pancreas. Galen's descriptions, that is, "Nature created 'so-called pancreas 'and spread it beneath all vessels" are not generally acceptable but propose the very rare portal vein anomalies. Since the early years of the 20th century, cases with a preduodenal portal vein or a prepancreatic portal vein have been reported. Although the incidence is very rare, its surgical importance is emphasized. Copyright © 2014

A Fate Map of the Murine Pancreas Buds Reveals a Multipotent Ventral Foregut Organ Progenitor

Science.gov (United States)

Angelo, Jesse R.; Guerrero-Zayas, Mara-Isel; Tremblay, Kimberly D.

2012-01-01

The definitive endoderm is the embryonic germ layer that gives rise to the budding endodermal organs including the thyroid, lung, liver and pancreas as well as the remainder of the gut tube. DiI fate mapping and whole embryo culture were used to determine the endodermal origin of the 9.5 days post coitum (dpc) dorsal and ventral pancreas buds. Our results demonstrate that the progenitors of each bud occupy distinct endodermal territories. Dorsal bud progenitors are located in the medial endoderm overlying somites 2–4 between the 2 and 11 somite stage (SS). The endoderm forming the ventral pancreas bud is found in 2 distinct regions. One territory originates from the left and right lateral endoderm caudal to the anterior intestinal portal by the 6 SS and the second domain is derived from the ventral midline of the endoderm lip (VMEL). Unlike the laterally located ventral foregut progenitors, the VMEL population harbors a multipotent progenitor that contributes to the thyroid bud, the rostral cap of the liver bud, ventral midline of the liver bud and the midline of the ventral pancreas bud in a temporally restricted manner. This data suggests that the midline of the 9.5 dpc thyroid, liver and ventral pancreas buds originates from the same progenitor population, demonstrating a developmental link between all three ventral foregut buds. Taken together, these data define the location of the dorsal and ventral pancreas progenitors in the prespecified endodermal sheet and should lead to insights into the inductive events required for pancreas specification. PMID:22815796

A 3D map of the islet routes throughout the healthy human pancreas

Science.gov (United States)

Ionescu-Tirgoviste, Constantin; Gagniuc, Paul A.; Gubceac, Elvira; Mardare, Liliana; Popescu, Irinel; Dima, Simona; Militaru, Manuella

2015-01-01

Islets of Langerhans are fundamental in understanding diabetes. A healthy human pancreas from a donor has been used to asses various islet parameters and their three-dimensional distribution. Here we show that islets are spread gradually from the head up to the tail section of the pancreas in the form of contracted or dilated islet routes. We also report a particular anatomical structure, namely the cluster of islets. Our observations revealed a total of 11 islet clusters which comprise of small islets that surround large blood vessels. Additional observations in the peripancreatic adipose tissue have shown lymphoid-like nodes and blood vessels captured in a local inflammatory process. Our observations are based on regional slice maps of the pancreas, comprising of 5,423 islets. We also devised an index of sphericity which briefly indicates various islet shapes that are dominant throughout the pancreas. PMID:26417671

Structural similarities and differences between the human and the mouse pancreas

Science.gov (United States)

Dolenšek, Jurij; Rupnik, Marjan Slak; Stožer, Andraž

2015-01-01

Mice remain the most studied animal model in pancreas research. Since the findings of this research are typically extrapolated to humans, it is important to understand both similarities and differences between the 2 species. Beside the apparent difference in size and macroscopic organization of the organ in the 2 species, there are a number of less evident and only recently described differences in organization of the acinar and ductal exocrine tissue, as well as in the distribution, composition, and architecture of the endocrine islets of Langerhans. Furthermore, the differences in arterial, venous, and lymphatic vessels, as well as innervation are potentially important. In this article, the structure of the human and the mouse pancreas, together with the similarities and differences between them are reviewed in detail in the light of conceivable repercussions for basic research and clinical application. PMID:26030186

Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells

OpenAIRE

Lee, Jonghyeob; Snyder, Emily R.; Liu, Yinghua; Gu, Xueying; Wang, Jing; Flowers, Brittany M.; Kim, Yoo Jung; Park, Sangbin; Szot, Gregory L.; Hruban, Ralph H.; Longacre, Teri A.; Kim, Seung K.

2017-01-01

Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring...

Improved application of the electrophoretic tissue clearing technology, CLARITY, to intact solid organs including brain, pancreas, liver, kidney, lung, and intestine.

Science.gov (United States)

Lee, Hyunsu; Park, Jae-Hyung; Seo, Incheol; Park, Sun-Hyun; Kim, Shin

2014-12-21

Mapping of tissue structure at the cellular, circuit, and organ-wide scale is important for understanding physiological and biological functions. A bio-electrochemical technique known as CLARITY used for three-dimensional anatomical and phenotypical mapping within transparent intact tissues has been recently developed. This method provided a major advance in understanding the structure-function relationships in circuits of the nervous system and organs by using whole-body clearing. Thus, in the present study, we aimed to improve the original CLARITY procedure and developed specific CLARITY protocols for various intact organs. We determined the optimal conditions for reducing bubble formation, discoloration, and depositing of black particles on the surface of tissue, which allowed production of clearer organ images. We also determined the appropriate replacement cycles of clearing solution for each type of organ, and convincingly demonstrated that 250-280 mA is the ideal range of electrical current for tissue clearing. We then acquired each type of cleared organs including brain, pancreas, liver, lung, kidney, and intestine. Additionally, we determined the images of axon fibers of hippocampal region, the Purkinje layer of cerebellum, and vessels and cellular nuclei of pancreas. CLARITY is an innovative biochemical technology for the structural and molecular analysis of various types of tissue. We developed improved CLARITY methods for clearing of the brain, pancreas, lung, intestine, liver, and kidney, and identified the appropriate experimental conditions for clearing of each specific tissue type. These optimized methods will be useful for the application of CLARITY to various types of organs.

Epidemiology of cancers of the liver, gall bladder, extrahepatic bile duct and pancreas in Nagasaki city from 1973 to 1982 with reference to atomic bomb exposure

International Nuclear Information System (INIS)

Takeshima, Fuminao; Shimokawa, Isao; Takashima, Kazuhiko

1990-01-01

This epidemiology study included 808 cases of liver cancers, 378 cases of gall bladder and extrahepatic bile duct cancer, and 312 cases of pancreas cancer registered at the Nagasaki Tumor Registry from 1973 to 1982, with emphasis on the relationship of these cancers to radiation exposure. The incidence of liver, gall bladder and extrahepatic bile duct cancer in both sexes tended to be higher in A-bomb survivors than in the nonexposed population, but were particularly significantly higher in male A-bomb survivors in each age-adjusted relative risk group. The incidence of pancreas cancer in females tended to be higher among A-bomb survivors than in the nonexposed population, and age-adjusted relative risk was significantly higher for female A-bomb survivors. No significant differences in relative distribution of histological type between exposed and nonexposed groups was observed. (author)

PET tomographic 2-D and/or 3-D imaging of nitrogen-13, derived from 13N-amino acids, in the heart, pancreas, liver

International Nuclear Information System (INIS)

Myers, W.G.; Bigler, R.E.; Gelbard, A.S.; Benua, R.S.; Graham, M.C.; Laughlin, J.S.

1982-01-01

The loci of accumulations of Nitrogen-13, derived from enzymatically-synthesized, intravenously-injected, natural L-forms of (N-13)-L-Glutamate, (N-13)-L-Leucine, (N-13)-L-Valine, or (N-13)-L-Methionine, were determined in situ in several organs after a large meal. The images were made with the first commercial version of the MGH ''positron'' camera. When operated in the transverse, coronal, 2-D mode, high concentrations of N-13 were found consistently in the Heart and Pancreas, and lesser amounts in the Liver, after (N-13)-Glutamate or (N-13)-L-Leucine. Little accumulation occurred in the Heart after (N-13)-L-Methionine or (N-13)-L-Valine. High concentrations of N-13 were found in the Pancreas after the (N-13)-L-Methionine or (N-13)-L-Valine. When the PCT-4200 instrument was operated in the 3-D orthogonal mode, following intravenous (N-13)-L-Glutamate, five transverse 1.0-cm-thick slice images were made at 1.4-cm sequential spacings, both of the Heart and of the Pancreas. The computer simultaneously collected the data for reconstrutions subsequently of all ten image slices through both the Heart and the Pancreas

In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection

NARCIS (Netherlands)

Bartfeld, Sina; Bayram, Tülay; van de Wetering, Marc; Huch, Meritxell; Begthel, Harry; Kujala, Pekka; Vries, Robert; Peters, Peter J; Clevers, Hans

BACKGROUND & AIMS: We previously established long-term, 3-dimensional culture of organoids from mouse tissues (intestine, stomach, pancreas, and liver) and human intestine and pancreas. Here we describe conditions required for long-term 3-dimensional culture of human gastric stem cells. The

Pancreas

Science.gov (United States)

... Page Transplant Living > Organ facts and surgeries > Pancreas Pancreas Beneath your ribs, you’ll find the pancreas, ... shape. Location of the pancreas How does the pancreas work? The pancreas controls your sugar levels and ...

Evaluation of the pancreas by MRI

International Nuclear Information System (INIS)

Imanishi, Yoshimasa; Hou, V.Y.; Chako, A.C.; Tempany, C.M.C.; Herold, C.J.; Zerhouni, E.A.

1994-01-01

Using T1-, P- and T2-weighted images of the upper abdomen obtained on 1.5 T MRI system, 18 items on the pancreas were evaluated in 89 controls. The items included pancreas sizes on T1-weighted image, pancreatic intensity compared with those of renal cortex, subcutaneous fat tissue, liver and spleen, obliteration of pancreas margin, and diameter of pancreatic duct on all images. Normal criteria, which were determined from data in the controls, were applied to images in the 40 patients with pancreatic or peripancreatic diseases. All 4 patients with an extrapancreatic tumor had no abnormality of pancreatic intensity, pancreatic margin, and pancreatic duct on T2-weighted image, except for pancreatic sizes and intensities at tumor sites. In contrast, 34 of 36 patients with pancreatic disease had abnormalities which pathologically depended on acute and/or chronic pancreatitis. (orig.)

Foxa1 reduces lipid accumulation in human hepatocytes and is down-regulated in nonalcoholic fatty liver.

Directory of Open Access Journals (Sweden)

Marta Moya

Full Text Available Triglyceride accumulation in nonalcoholic fatty liver (NAFL results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2 however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB. Moreover, Foxa1 represses the fatty acid transporter protein FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing peroxisomal fatty acid β-oxidation and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolic pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance.

Trends in cancer of the liver, gall bladder, bile duct, and pancreas in elderly in Denmark, 1980-2012

DEFF Research Database (Denmark)

Bjerregaard, Jon Kroll; Mortensen, Michael Bau; Pfeiffer, Per

2016-01-01

, mortality, prevalence and relative survival for these cancers.Materials and methods HBP-c was defined as ICD-10 codes C22 (liver), C23-24 (gall bladder), and C25 (pancreas). Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival.......Conclusion As the number of persons aged 80 years or more will increase dramatically in the following years, and our results show a gap in relative survival, it is important to continue to study this population in order to improve management and outcome....

Physiology and pathophysiology of apoptosis in epithelial cells of the liver, pancreas, and intestine.

Science.gov (United States)

Jones, B A; Gores, G J

1997-12-01

Cell death of gastrointestinal epithelial cells occurs by a process referred to as apoptosis. In this review, we succinctly define apoptosis and summarize the role of apoptosis in the physiology and pathophysiology of epithelial cells in the liver, pancreas, and small and large intestine. The physiological mediators regulating apoptosis in gastrointestinal epithelial cells, when known, are discussed. Selected pathophysiological consequences of excessive apoptosis and inhibition of apoptosis are used to illustrate the significance of apoptosis in disease processes. These examples demonstrate that excessive apoptosis may result in epithelial cell atrophy, injury, and dysfunction, whereas inhibition of apoptosis results in hyperplasia and promotes malignant transformation. The specific cellular mechanisms responsible for dysregulation of epithelial cell apoptosis during pathophysiological disturbances are emphasized. Potential future areas of physiological research regarding apoptosis in gastrointestinal epithelia are highlighted when appropriate.

Tissue-specific deletion of c-Jun in the pancreas has limited effects on pancreas formation

International Nuclear Information System (INIS)

Yamamoto, Kaoru; Miyatsuka, Takeshi; Tanaka, Ayako; Toyoda, Shuichi; Kato, Ken; Shiraiwa, Toshihiko; Fujitani, Yoshio; Yamasaki, Yoshimitsu; Hori, Masatsugu; Matsuhisa, Munehide; Matsuoka, Taka-aki; Kaneto, Hideaki

2007-01-01

It is well known that activating protein-1 (AP-1) is involved in a variety of cellular functions such as proliferation, differentiation, apoptosis, and oncogenesis. AP-1 is a dimer complex consisting of different subunits, and c-Jun is known to be one of its major components. In addition, it has been shown that mice lacking c-Jun are embryonic lethal and that c-Jun is essential for liver and heart development. However, the role of c-Jun in the pancreas is not well known. The aim of this study was to examine the possible role of c-Jun in the pancreas. First, c-Jun was strongly expressed in pancreatic duct-like structures at an embryonic stage, while a lower level of expression was observed in some part of the adult pancreas, implying that c-Jun might play a role during pancreas development. Second, to address this point, we generated pancreas-specific c-Jun knock-out mice (Ptf1a-Cre; c-Jun flox/flox mice) by crossing Ptf1a-Cre knock-in mice with c-Jun floxed mice. Ptf1a is a pancreatic transcription factor and its expression is confined to pancreatic stem/progenitor cells, which give rise to all three types of pancreatic tissue: endocrine, exocrine, and duct. Contrary to our expectation, however, there was no morphological difference in the pancreas between Ptf1a-Cre; c-Jun flox/flox and control mice. In addition, there was no difference in body weight, pancreas weight, and the expression of various pancreas-related factors (insulin, glucagon, cytokeratin, and amylase) between the two groups. Furthermore, there was no difference in glucose tolerance between Ptf1a-Cre; c-Jun flox/flox and control mice. Taken together, although we cannot exclude the possibility that c-Jun ablation is compensated by some unknown factors, c-Jun appears to be dispensable for pancreas development at least after ptf1a gene promoter is activated

A comparative immunohistochemical study on amylase localization in the rat and human exocrine pancreas

International Nuclear Information System (INIS)

Aughsteen, Adib A.

2001-01-01

Objective was to localize amylase enzyme immunohistochemically in the pancreatic acinar cells of rats and humans using polyclonal sheep anti-human amylase antibody, and to compare between the intensities of their amylase-immunostaining. Indirect immunofluorescence method was applied on formaldehyde-fixed, and paraffin-embedded pancreatic sections obtained from adult male Wistar rats and autopsied human samples. Primary incubation was performed using sheep anti-amylase antibody followed by secondary incubation with fluorescein isothiocyanate-labeled rabbit anti-sheep IgG serum. Control tests of amylase immunospecificity were also undertaken either by incubation with primary antibodies previously pre-adsorbed with an excess of human pancreatic amylase, or only with secondary antibodies. The amylase immunofluorescence was positively and homogenously detected in all acinar cells of both rat and human pancreatic stained sections. The immunostaining was clearly demonstrated in the cell apices and peri-nuclear areas, but it was consistently brighter and more intense in the human acinar cells compared with that of the rat pancreas. Control tests of amylase immunofluorescence revealed the specificity of the antibodies applied for amylase localization in rat and human pancreas. Although many previous immunohisto- and cytochemical reports have successfully localized amylase in the pancreas of different mammalian species, but all of them have used locally prepared anti-amylase antibodies. The present report successfully illustrates immuno-localization of amylase in the pancreatic acinar cells of rats and humans using commercial polyclonal sheep anti-human pancreatic amylase antibodies, and also suggests their useful application in the immunochemical studies on various mammalian species. Additionally, the results indicate a structural similarity between the human and rat pancreatic amylases, a concept required further exploration. (author)

Analyses of pancreas development by generation of gfp transgenic zebrafish using an exocrine pancreas-specific elastaseA gene promoter

International Nuclear Information System (INIS)

Wan Haiyan; Korzh, Svitlana; Li Zhen; Mudumana, Sudha Puttur; Korzh, Vladimir; Jiang Yunjin; Lin Shuo; Gong Zhiyuan

2006-01-01

In contrast to what we know on development of endocrine pancreas, the formation of exocrine pancreas remains poorly understood. To create an animal model that allows observation of exocrine cell differentiation, proliferation, and morphogenesis in living animals, we used the zebrafish elastaseA (elaA) regulatory sequence to develop transgenic zebrafish that display highly specific exocrine pancreas expression of GFP in both larvae and adult. By following GFP expression, we found that the pancreas in early development was a relatively compact organ and later extended posterior along the intestine. By transferring the elaA:gfp transgene into slow muscle omitted mutant that is deficient in receiving Hedgehog signals, we further showed that Hedgehog signaling is required for exocrine morphogenesis but not for cell differentiation. We also applied the morpholino knockdown and toxin-mediated cell ablation approaches to this transgenic line. We showed that the development of exocrine pancreas is Islet-1 dependent. Injection of the diphtheria toxin A (DTA) construct under the elastaseA promoter resulted in selective ablation of exocrine cells while the endocrine cells and other endodermal derivatives (liver and intestine) were not affected. Thus, our works demonstrated the new transgenic line provided a useful experimental tool in analyzing exocrine pancreas development

Mn-DPDP, the first contrast agent for the pancreas

International Nuclear Information System (INIS)

Gehl, H.B.; Vorwerk, D.; Klose, K.C.; Raber, H.; Guenther, R.W.

1990-01-01

Mn-DPDP, known as a contrast agent for the hepatobiliary system, shows signal intensity increase of the pancreas as well. This paper describes the extent of signal intensity increase in the pancreas as a function of time. Six healthy volunteers were imaged with a 1.5-T MR unit using a T1-weighted gradient-echo sequence. Acquisitions were taken in 3-minute intervals for the first 45 minutes, followed by intervals of 30 minutes for 7 hours after infusion of Mn-DPDP. As a special formulation, 10 μmol per kg Mn-DPDP were infused. The enhancement of the head and the tail of the pancreas were measured and plotted as a function of time; the percentage increase in pancreas signal intensity was calculated and compared with the increase in liver signal intensity

Knowledge Gaps in Rodent Pancreas Biology: Taking Human Pluripotent Stem Cell-Derived Pancreatic Beta Cells into Our Own Hands.

Science.gov (United States)

Santosa, Munirah Mohamad; Low, Blaise Su Jun; Pek, Nicole Min Qian; Teo, Adrian Kee Keong

2015-01-01

In the field of stem cell biology and diabetes, we and others seek to derive mature and functional human pancreatic β cells for disease modeling and cell replacement therapy. Traditionally, knowledge gathered from rodents is extended to human pancreas developmental biology research involving human pluripotent stem cells (hPSCs). While much has been learnt from rodent pancreas biology in the early steps toward Pdx1(+) pancreatic progenitors, much less is known about the transition toward Ngn3(+) pancreatic endocrine progenitors. Essentially, the later steps of pancreatic β cell development and maturation remain elusive to date. As a result, the most recent advances in the stem cell and diabetes field have relied upon combinatorial testing of numerous growth factors and chemical compounds in an arbitrary trial-and-error fashion to derive mature and functional human pancreatic β cells from hPSCs. Although this hit-or-miss approach appears to have made some headway in maturing human pancreatic β cells in vitro, its underlying biology is vaguely understood. Therefore, in this mini-review, we discuss some of these late-stage signaling pathways that are involved in human pancreatic β cell differentiation and highlight our current understanding of their relevance in rodent pancreas biology. Our efforts here unravel several novel signaling pathways that can be further studied to shed light on unexplored aspects of rodent pancreas biology. New investigations into these signaling pathways are expected to advance our knowledge in human pancreas developmental biology and to aid in the translation of stem cell biology in the context of diabetes treatments.

The molecular and morphogenetic basis of pancreas organogenesis

DEFF Research Database (Denmark)

Larsen, Hjalte List; Grapin-Botton, Anne

2017-01-01

The pancreas is an essential endoderm-derived organ that ensures nutrient metabolism via its endocrine and exocrine functions. Here we review the essential processes governing the embryonic and early postnatal development of the pancreas discussing both the mechanisms and molecules controlling...... review of human pancreas development (Jennings et al., 2015) [1]. The understanding of pancreas development in model organisms provides a framework to interpret how human mutations lead to neonatal diabetes and may contribute to other forms of diabetes and to guide the production of desired pancreatic...

Structure of neuro-endocrine and neuro-epithelial interactions in human foetal pancreas.

Science.gov (United States)

Krivova, Yuliya; Proshchina, Alexandra; Barabanov, Valeriy; Leonova, Olga; Saveliev, Sergey

2016-12-01

In the pancreas of many mammals including humans, endocrine islet cells can be integrated with the nervous system components into neuro-insular complexes. The mechanism of the formation of such complexes is not clearly understood. The present study evaluated the interactions between the nervous system components, epithelial cells and endocrine cells in the human pancreas. Foetal pancreas, gestational age 19-23 weeks (13 cases) and 30-34 weeks (7 cases), were studied using double immunohistochemical labeling with neural markers (S100 protein and beta III tubulin), epithelial marker (cytokeratin 19 (CK19)) and antibodies to insulin and glucagon. We first analyse the structure of neuro-insular complexes using confocal microscopy and provide immunohistochemical evidences of the presence of endocrine cells within the ganglia or inside the nerve bundles. We showed that the nervous system components contact with the epithelial cells located in ducts or in clusters outside the ductal epithelium and form complexes with separate epithelial cells. We observed CK19-positive cells inside the ganglia and nerve bundles which were located separately or were integrated with the islets. Therefore, we conclude that neuro-insular complexes may forms as a result of integration between epithelial cells and nervous system components at the initial stages of islets formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

MR imaging evaluation of pancreas and hepatobiliary system in cystic fibrosis

International Nuclear Information System (INIS)

Murayama, S.; Robinson, A.E.; Stallworth, J.; Mulvihill, D.; Beckerman, R.; Davis, S.

1988-01-01

The pancreas and hepatobiliary system of 20 patients with cystic fibrosis were analyzed with a 1.5-T magnet. T1-weighted, T2-weighted, and proton-density images were obtained, and the T1 and T2 values of the pancreas were calculated. Signal intensity ratios were calculated for the signal intensities of the pancreas and the liver relative to that of muscle and fat on each pulse sequence. Fatty replacement of the pancreas and regenerating nodules of biliary cirrhosis were readily identified on T1-weighted images. The T1 values for pancreatic tissue showed promise as a good marker for pancreatic disease progression. Pancreas-to-fat signal intensity ratios on 300/20 (repetition time msec/echo time msec) and 2,000/75 images were considered to be a good standard for evaluating the level of pancreatic involvement

MicroRNA signature of the human developing pancreas

Directory of Open Access Journals (Sweden)

Correa-Medina Mayrin

2010-09-01

Full Text Available Abstract Background MicroRNAs are non-coding RNAs that regulate gene expression including differentiation and development by either inhibiting translation or inducing target degradation. The aim of this study is to determine the microRNA expression signature during human pancreatic development and to identify potential microRNA gene targets calculating correlations between the signature microRNAs and their corresponding mRNA targets, predicted by bioinformatics, in genome-wide RNA microarray study. Results The microRNA signature of human fetal pancreatic samples 10-22 weeks of gestational age (wga, was obtained by PCR-based high throughput screening with Taqman Low Density Arrays. This method led to identification of 212 microRNAs. The microRNAs were classified in 3 groups: Group number I contains 4 microRNAs with the increasing profile; II, 35 microRNAs with decreasing profile and III with 173 microRNAs, which remain unchanged. We calculated Pearson correlations between the expression profile of microRNAs and target mRNAs, predicted by TargetScan 5.1 and miRBase altgorithms, using genome-wide mRNA expression data. Group I correlated with the decreasing expression of 142 target mRNAs and Group II with the increasing expression of 876 target mRNAs. Most microRNAs correlate with multiple targets, just as mRNAs are targeted by multiple microRNAs. Among the identified targets are the genes and transcription factors known to play an essential role in pancreatic development. Conclusions We have determined specific groups of microRNAs in human fetal pancreas that change the degree of their expression throughout the development. A negative correlative analysis suggests an intertwined network of microRNAs and mRNAs collaborating with each other. This study provides information leading to potential two-way level of combinatorial control regulating gene expression through microRNAs targeting multiple mRNAs and, conversely, target mRNAs regulated in

Transcriptional ontogeny of the developing liver

Directory of Open Access Journals (Sweden)

Lee Janice S

2012-01-01

Full Text Available Abstract Background During embryogenesis the liver is derived from endodermal cells lining the digestive tract. These endodermal progenitor cells contribute to forming the parenchyma of a number of organs including the liver and pancreas. Early in organogenesis the fetal liver is populated by hematopoietic stem cells, the source for a number of blood cells including nucleated erythrocytes. A comprehensive analysis of the transcriptional changes that occur during the early stages of development to adulthood in the liver was carried out. Results We characterized gene expression changes in the developing mouse liver at gestational days (GD 11.5, 12.5, 13.5, 14.5, 16.5, and 19 and in the neonate (postnatal day (PND 7 and 32 compared to that in the adult liver (PND67 using full-genome microarrays. The fetal liver, and to a lesser extent the neonatal liver, exhibited dramatic differences in gene expression compared to adults. Canonical pathway analysis of the fetal liver signature demonstrated increases in functions important in cell replication and DNA fidelity whereas most metabolic pathways of intermediary metabolism were under expressed. Comparison of the dataset to a number of previously published microarray datasets revealed 1 a striking similarity between the fetal liver and that of the pancreas in both mice and humans, 2 a nucleated erythrocyte signature in the fetus and 3 under expression of most xenobiotic metabolism genes throughout development, with the exception of a number of transporters associated with either hematopoietic cells or cell proliferation in hepatocytes. Conclusions Overall, these findings reveal the complexity of gene expression changes during liver development and maturation, and provide a foundation to predict responses to chemical and drug exposure as a function of early life-stages.

Apoptosis of acinar cells in pancreas allograft rejection

NARCIS (Netherlands)

Boonstra, J. G.; Wever, P. C.; Laterveer, J. C.; Bruijn, J. A.; van der Woude, F. J.; ten Berge, I. J.; Daha, M. R.

1997-01-01

BACKGROUND: Recently it has been recognized that apoptosis of target cells may occur during liver and kidney allograft rejection and is probably induced by infiltrating cells. Pancreas rejection is also characterized by a cellular infiltrate, however, the occurrence of apoptosis has not been

An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas.

Science.gov (United States)

Korsgren, Erik; Korsgren, Olle

2016-04-01

The lymphatic system is crucial for efficient immune surveillance and for the maintenance of a physiological pressure in the interstitial space. Even so, almost no information is available concerning the lymph drainage of the islets of Langerhans in the human pancreas. Immunohistochemical staining allowed us to distinguish lymphatic capillaries from blood capillaries. Almost no lymphatic capillaries were found within the islets in pancreatic biopsy specimens from subjects without diabetes or from subjects with type 1 or type 2 diabetes. Lymphatic capillaries were, however, found at the islet-exocrine interface, frequently located along blood capillaries and other fibrotic structures within or close to the islet capsule. Lymphatic capillaries were regularly found in the exocrine pancreas, with small lymphatic vessels located close to and around acini. Larger collecting lymphatic vessels were located in fibrotic septa between the exocrine lobules and adjacent to the ductal system of the pancreas. In summary, we report a pronounced deficiency of lymphatic capillaries in human islets, a finding with implications for immune surveillance and the regulation of interstitial fluid transport in the endocrine pancreas as well as for the pathophysiology of both type 1 and type 2 diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

A pancreas imaging agent-131I-HIPDM: the animal experiment and preliminary clinical application

International Nuclear Information System (INIS)

Shao Hesheng

1988-01-01

131 I-HIPDM has been used clinically for studying regional cerebral perfusion. The [ 131 I] HIPDM was prepared in a kit. The labelling yields were consistently more than 95%, as analyzed by the TLC-Silica gel. The labelled compound is stable in vitro and in vivo. S D Strain rats (170-220 g) and mice (18-22 g) were used. The pancreatic uptake of [ 131 I] HIPDM is rather slow in mice and rats. At 8 hr after iv, the pancreas activity and the pancreas to liver (P/L) ratio are highest in mice and rats. The effect of carrier loading dose from 0.010 to 6.0 mg/kg on blodistribution in mice has been studied. The liver uptake was increased by adding carrier HIPDM. The result indicates that administration between 0.010 and 0.05 mg/kg carrier dose is most suitable for the pancreas imaging. Gamma camera imaging of dog at 6 hr after iv with 300 μCi [ 131 I] HIPMD, 0.05 mg/kg body weight showed clear pancreas image. The P/L ratio of the dog is 0.40. Preliminary clinical tests were satisfactory. Using 1 to 1.5 mCi of [ 131 I] HIPDM, 0.05 mg/kg, the pancreas imaging was operated in 4 cases of volunteers and pancreas cyst respectively with the good diagnostic quality. The authors are of the opinion that this pancreas imaging agent may have potential value for routine use

MRI of the cystic mass lesions of the pancreas

International Nuclear Information System (INIS)

Ohtomo, Kuni; Itai, Yuji; Yoshikawa, Koki; Kokubo, Takashi; Yashiro, Naofumi; Iio, Masahiro

1987-01-01

Five cystic mass lesions of the pancreas were exemined by MRI. Multiplocular fluid components were demonstrated as areas of various signal intensity in mucinous cystadenoma and cystadenocarcinoma. Gas within the cystic mass was noted in ductectatic mucinous cystadenocarcinoma. Honeycomb pattern and classification were not depicted in serous cystadenoma. Necrotic matter was demonstrated as area of lower signal than liver in pseudocyst. These results were then compared with CT and ultrasound and at present enhanced CT combined with ultrasound is more diagnostic than MRI for cystic mass lesions of the pancreas. (author)

Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas.

Science.gov (United States)

Saisho, Yoshifumi

2016-01-01

The pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the natural history of diabetes. In both patients with T1D and those with T2D, pancreas mass and exocrine function have been reported to be reduced. On the other hand, pancreas volume and pancreatic fat increase with obesity. Increased beta-cell mass with increasing obesity has also been observed in humans, and ectopic fat deposits in the pancreas have been reported to cause beta-cell dysfunction. Moreover, neogenesis and transdifferentiation from the exocrine to the endocrine compartment in the postnatal period are regarded as a source of newly formed beta-cells. These findings suggest that there is important interplay between the endocrine and exocrine pancreas throughout life. This review summarizes the current knowledge on physiological and pathological changes in the exocrine and endocrine pancreas (i.e., beta-cell mass), and discusses the potential mechanisms of the interplay between the two compartments in humans to understand the pathophysiology of diabetes better.

Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas

Science.gov (United States)

Saisho, Yoshifumi

2016-01-01

The pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the natural history of diabetes. In both patients with T1D and those with T2D, pancreas mass and exocrine function have been reported to be reduced. On the other hand, pancreas volume and pancreatic fat increase with obesity. Increased beta-cell mass with increasing obesity has also been observed in humans, and ectopic fat deposits in the pancreas have been reported to cause beta-cell dysfunction. Moreover, neogenesis and transdifferentiation from the exocrine to the endocrine compartment in the postnatal period are regarded as a source of newly formed beta-cells. These findings suggest that there is important interplay between the endocrine and exocrine pancreas throughout life. This review summarizes the current knowledge on physiological and pathological changes in the exocrine and endocrine pancreas (i.e., beta-cell mass), and discusses the potential mechanisms of the interplay between the two compartments in humans to understand the pathophysiology of diabetes better. PMID:28012279

Computed tomography of pancreas in diabetic patients in relation to diabetic retinopathy

International Nuclear Information System (INIS)

Katsumata, K.; Katsumata, Y.; Sakuma, S.; Kaii, O.; Shimamoto, K.; Hirabayashi, N.; Nakagawa, T.

1987-01-01

Lipomatous pancreas is hardly diagnosed in living humans and usually recognized at autopsy. In the present work, it is proposed that lipomatous pancreas can be diagnosed in living humans by computed tomography (CT) of the pancreas. 2 refs.; 1 figure

Getting a New Pancreas: Facts about Pancreas Transplants

Science.gov (United States)

... 2003 December 2006 March 2012 Getting A New Pancreas Facts About Pancreas Transplants American Society of Transplantation 1120 Route 73, ... the views of the Society. _________________________________________________________________ Getting a New Pancreas Facts About Pancreas Transplants When you get a ...

in Human Liver Diseases

Directory of Open Access Journals (Sweden)

Minoru Fujimoto

2010-01-01

Full Text Available Toll-like receptor (TLR signaling pathways are strictly coordinated by several mechanisms to regulate adequate innate immune responses. Recent lines of evidence indicate that the suppressor of cytokine signaling (SOCS family proteins, originally identified as negative-feedback regulators in cytokine signaling, are involved in the regulation of TLR-mediated immune responses. SOCS1, a member of SOCS family, is strongly induced upon TLR stimulation. Cells lacking SOCS1 are hyperresponsive to TLR stimulation. Thus, SOCS1 is an important regulator for both cytokine and TLR-induced responses. As an immune organ, the liver contains various types of immune cells such as T cells, NK cells, NKT cells, and Kupffer cells and is continuously challenged with gut-derived bacterial and dietary antigens. SOCS1 may be implicated in pathophysiology of the liver. The studies using SOCS1-deficient mice revealed that endogenous SOCS1 is critical for the prevention of liver diseases such as hepatitis, cirrhosis, and cancers. Recent studies on humans suggest that SOCS1 is involved in the development of various liver disorders in humans. Thus, SOCS1 and other SOCS proteins are potential targets for the therapy of human liver diseases.

Intrapancreatic Splenule in a Pancreas Allograft: Case Report.

Science.gov (United States)

Yadav, K; Serrano, O K; Kandaswamy, R

2016-11-01

A 16-year-old white man was involved in a motor vehicle collision and suffered head, chest, and abdominal trauma. Despite initial resuscitative efforts, he progressed to brain death and was designated to be an organ donor by his family. He had no earlier medical or surgical history and no high-risk behaviors. Blood work revealed normal creatinine, liver function tests, lipase, and amylase. Viral serologies were negative except for cytomegalovirus IgG and Epstein-Barr virus nucleic acid. Imaging revealed a right kidney contusion, a manubrial fracture, and fractures of right first rib and bilateral scapulae. No other abdominal trauma was identified, specifically to the pancreas, duodenum, or spleen. Our transplant center accepted the pancreas from this donor. During back-table inspection of the pancreas, a 1.5 × 1.5 cm dark purple rubbery mass was identified within the parenchyma of the pancreas in the tail. An incisional biopsy of the lesion was sent for frozen section, which yielded a mixed inflammatory infiltrate consisting of neutrophils and lymphocytes and an overlying fibrous capsule. The diagnosis of lymphoma or another neoplasm could not be definitely ruled out. Owing to uncertainty in diagnosis, the entire lesion was excised along with the distal pancreas with the use of a linear stapler. The staple line was oversewn with running 4-0 polypropylene suture, and the pancreas was transplanted. After surgery, the pancreas allograft functioned well with a small pancreatic leak, which had resolved by the first postoperative outpatient visit. Published by Elsevier Inc.

Accompanying role of hepato-biliary-pancreas surgeon in urological surgery

Directory of Open Access Journals (Sweden)

Atsushi Nanashima

Full Text Available Introduction: The present case reports demonstrated the accompanying surgical support from hepato-biliary-pancreas (HBP surgeons for urological surgery to secure operative safety because HBP surgeons are well experienced in dissecting techniques for mobilization of the liver or pancreas. We experienced 9 consecutive patients who underwent nephrectomy, adrenectomy or resection of retroperitoneal tumors by urological surgeons. Cardiovascular intervention was also required in cases of long tumor thrombus into the vena cava. Cases: All patients had no severe co-existing diseases except the main tumor. Reverse T-shape incision was performed in 7 cases and thoracolaparotomy in two. Dissection and mobilization at the site of severe compression by the urinary tumors were performed in three cases. Partial liver resection was performed for testicular liver metastases in two, and right hepatectomy for right renal cancer was performed in one. Encircling the vena cava and preparation of transection for tumor thrombi were performed in three, and among these, cardiovascular intervention was necessary in two because of extension into the right atrium. During admission, all patient outcomes were uneventful without severe complications. We herein showed the representative two cases of combined surgery. Discussion: and conclusion The point of this case report is the coordination between each surgeon and anesthesiologist under precise perioperative planning or management. The role of HBP surgeons is to provide information as a specialist on the operative field for urological or cardiovascular surgery to achieve operative safety. Keywords: Hepato-biliary-pancreas surgeon, Joint surgery, Urology

Complete agenesis of the dorsal pancreas: Case report with ...

African Journals Online (AJOL)

pancreatic head and uncinate process were normal, but the distal neck, body ... The neck, body, tail, and cephalic aspects of the head of the pancreas originate from the .... Embryology, normal variation, and congenital anomalies of the pancreas. ... M. A 3D reconstruction of pancreas development in the human embryos.

A New Technique for Scanning the Pancreas

Energy Technology Data Exchange (ETDEWEB)

Ephraiem, K. H. [Rotterdamsch Radio-Therapeutisch Instituut, Rotterdam (Netherlands)

1969-05-15

The difficulties in visualizing the pancreas are partly caused by the high uptake of seleno-methionine in the liver. A simple technique has been developed to prevent data registration during the time the detector is moving above the liver. The technique is based on the fact that both {sup 75}Se and {sup 99m}Tc emit gamma rays of 140-keV energy. The pulses, normally going from the single-channel analyser to the registrating units, are deviated through a ratemeter to an API contactless optical meter relay (model API-compack I) and then passed on to the registrating units. The patient is given the normal dose of Se-methionine and everything is prepared for normal pancreas scanning with only one exception: The window of the single-channel analyser is tuned in on the 140-keV photopeak. The patient is given 2 mCi of {sup 99m}Tc colloid intravenously and the controls on the meter relay are adjusted in such a way that no pulse from the single-channel analyser passes to the registrating units unless the activity is beneath the activity level in the liver. Then the scanning machine is started. The author developed this inexpensive technique to help smaller clinical isotope laboratories which cannot afford the combination of a gamma camera with a special-purpose computer. (author)

The pancreas in {beta}-thalassemia major: MR imaging features and correlation with iron stores and glucose disturbunces

Energy Technology Data Exchange (ETDEWEB)

Papakonstantinou, Olympia [University Hospital of Heraklion, Medical School of Crete, Department of Radiology, Heraklion, Crete (Greece); Attikon Hospital, 2nd Department of Radiology, Athens (Greece); Ladis, Vasilios; Kostaridou, Stavroula; Berdousi, Helen; Kattamis, Christos [Thalassemia Unit, University of Athens, ' ' Aghia Sophia' ' Children' s Hospital, Athens (Greece); Maris, Thomas; Gourtsoyiannis, Nicholas [University Hospital of Heraklion, Medical School of Crete, Department of Radiology, Heraklion, Crete (Greece)

2007-06-15

The study aims at describing the MR features of pancreas in beta-thalassemia major, investigating the relations between MR findings and glucose disturbances and between hepatic and pancreatic siderosis. Signal intensity ratios of the pancreas and liver to right paraspinous muscle (P/M, L/M) were retrospectively assessed on abdominal MR imaging studies of 31 transfusion-dependent patients with beta-thalassemia major undergoing quantification of hepatic siderosis and 10 healthy controls, using T1- (120/4/90), intermediate in and out of phase - (120/2.7, 4/20), and T2*-(120/15/20) weighted GRE sequences. Using the signal drop of the liver and pancreas on opposed phase images, we recorded serum ferritin and results of oral glucose tolerance test (OGTT). Decreased L/M and P/M on at least the T2* sequence were noticed in 31/31 and 30/31 patients, respectively, but no correlation between P/M and L/M was found. Patients with pathologic OGTT displayed a higher degree of hepatic siderosis (p < 0.04) and signal drop of pancreas on opposed phase imaging (p < 0.025), implying fatty replacement of pancreas. P/M was neither correlated with glucose disturbances nor serum ferritin. Iron deposition in the pancreas cannot be predicted by the degree of hepatic siderosis in beta-thalassemia major. Fatty replacement of the pancreas is common and may be associated with glucose disturbances. (orig.)

The pancreas in β-thalassemia major: MR imaging features and correlation with iron stores and glucose disturbunces

International Nuclear Information System (INIS)

Papakonstantinou, Olympia; Ladis, Vasilios; Kostaridou, Stavroula; Berdousi, Helen; Kattamis, Christos; Maris, Thomas; Gourtsoyiannis, Nicholas

2007-01-01

The study aims at describing the MR features of pancreas in beta-thalassemia major, investigating the relations between MR findings and glucose disturbances and between hepatic and pancreatic siderosis. Signal intensity ratios of the pancreas and liver to right paraspinous muscle (P/M, L/M) were retrospectively assessed on abdominal MR imaging studies of 31 transfusion-dependent patients with beta-thalassemia major undergoing quantification of hepatic siderosis and 10 healthy controls, using T1- (120/4/90), intermediate in and out of phase - (120/2.7, 4/20), and T2*-(120/15/20) weighted GRE sequences. Using the signal drop of the liver and pancreas on opposed phase images, we recorded serum ferritin and results of oral glucose tolerance test (OGTT). Decreased L/M and P/M on at least the T2* sequence were noticed in 31/31 and 30/31 patients, respectively, but no correlation between P/M and L/M was found. Patients with pathologic OGTT displayed a higher degree of hepatic siderosis (p < 0.04) and signal drop of pancreas on opposed phase imaging (p < 0.025), implying fatty replacement of pancreas. P/M was neither correlated with glucose disturbances nor serum ferritin. Iron deposition in the pancreas cannot be predicted by the degree of hepatic siderosis in beta-thalassemia major. Fatty replacement of the pancreas is common and may be associated with glucose disturbances. (orig.)

Solid and cystic pseudopapillary tumor of the pancreas: A case report

Directory of Open Access Journals (Sweden)

Milošević Bojan Z.

2013-01-01

Full Text Available Introduction. Solid and cystic pseudopapillary tumor of the pancreas is a rare tumor of the pancreas, for the first time described by Frantz et al. in 1959. The majority of patients are young females and most of them are asymptomatic. Case Outline. We report a case of 25-year old woman who was admitted to our institution with abdominal pain and a palpable mass in the left hypochondrial area. US and CT scan revealed a solid and cystic pseudopapillary tumor in the head of the pancreas. The patient was treated by Whipple procedure, modification Longmire-Traverso. There was no metastatic disease either in the liver or peritoneum. Histologically the tumor was diagnosed as a solid and cystic pseudopapillary tumor of the pancreas. Conclusion. The unclear pre-operative diagnoses, together with incidence of potential malignancy as well as good outcome with resection, suggest that all suspected cystic tumors of the pancreas should be resected. The exact diagnosis is based on histological findings. [Projekat Ministarstva nauke Republike Srbije, br. III41007 i br. III41010

Fibromyxoid sarcoma of the pancreas

Directory of Open Access Journals (Sweden)

Čolović Radoje

2008-01-01

Full Text Available Introduction Fibromyxoid sarcoma is a rare mesenchymal neoplasm, usually appearing in the soft tissue of the extremities, less frequently in the groin, trunk, neck, and upper extremities. Within the abdomen, the tumour is usually localised within the retroperitoneum. Case OutlineWe present a 56-year-old woman in whom, during the routinely performed investigation for atacks of choking with lots of bronchial secretion, and arterial hypertension, an ultrasonographer found a tumour within the head of the pancreas 6×6 cm in diameter. At operation, a dark pink, lobulated soft tumour, surrounded by a tiny capsule, clearly different from the completely normal pancreatic tissue of the posterior side of the head of the pancreas, was easily and ideally excised.The postoperative recovery was stormy. She developed postoperative pancreatitis, temporary biliary and duodenal fistula, which all settled by conservative treatment. The histology of the 80 g weighing tumour showed a circumscribed fibromyxoid sarcoma of low malignancy. Immunohistochemistry showed diffuse vimentin and CD34 strong positivity, as well as focal anti-SMA and anti-EMA immunopositivity. Six months after surgery, she died with signs of cerebrovascular insult, asthmatic status, and recurrent suppurative abdominal fistula, probably related to the previous pancreatitis. Ultrasonography showed a possible liver secondary. The exact cause of death was not confirmed as the autopsy was refused by the family. Conclusion Primary sarcomas of the pancreas are very rare, but should be considered in differential diagnosis of pancreatic neoplasms. To the best of our knowledge, there has been no previously described fibromyxoid sarcoma of the pancreas. .

Pancreas and liver resection in Jehovah's Witness patients: feasible and safe.

Science.gov (United States)

Konstantinidis, Ioannis T; Allen, Peter J; D'Angelica, Michael I; DeMatteo, Ronald P; Fischer, Mary E; Grant, Florence; Fong, Yuman; Kingham, T Peter; Jarnagin, William R

2013-12-01

Jehovah's Witness (JW) patients undergoing liver or pancreas surgery represent a challenging ethical and medical problem, with few reports about their optimal management. To analyze the perioperative outcomes of JW patients submitted to hepatic or pancreatic resection, clinicopathologic data of JW patients who underwent surgical exploration for a hepatic or pancreatic tumor between March 1996 and July 2011 were reviewed retrospectively. Clinicopathologic data of 27 patients, 28 explorations, and 25 resections were included. Median age was 58 years (range 28 to 75 years) and 20 patients were female. Three patients were explored and deemed unresectable. Fifteen hepatic resections (9 segmentectomy or bi/trisegmentectomy, 6 hemi-hepatectomy or extended hepatectomy) and 10 pancreatic resections (6 pancreaticoduodenectomy, 4 distal pancreatectomy/splenectomy) were reviewed; additional organs were resected in 5 patients (2 gastrectomy, 1 colectomy, 1 nephrectomy, 1 adrenalectomy, 1 salpingoophorectomy). Median estimated blood loss for the hepatectomies was 400 mL (range 100 to 1,500 mL) and for the pancreatectomies was 400 mL (range 250 to 1,800 mL). Six patients received preoperative erythropoietin; hemodilution was used in 9 patients and 3 had Cell Saver-generated autotransfusions. Median preoperative hemoglobin was 12.5 g/dL (range 9.5 to 14.4 g/dL) and median postoperative hemoglobin was 10.4 g/dL (range 9 to 12.4 g/dL). In-hospital mortality was 0%. One patient required re-exploration for decreasing hemoglobin and refusal of transfusion; a total of 11 complications developed in 7 other patients (5 wound infection/breakdown, 1 urinary tract infection, 1 ileus, 1 nausea/vomiting, 1 lymphedema, 1 ascites, and 1 ARDS). Median hospital stay was 7 days (range 4 to 23 days). Pancreatic and liver resection can be done safely in selected JW patients who refuse blood products by using a variety of blood-conservation techniques to help spare red cell mass. Copyright © 2013

A 3D reconstruction of pancreas development in the human embryos during embryonic period (Carnegie stages 15-23).

Science.gov (United States)

Radi, M; Gaubert, J; Cristol-Gaubert, R; Baecker, V; Travo, P; Prudhomme, M; Godlewski, G; Prat-Pradal, D

2010-01-01

The goal in this paper was to rebuild a three dimensional (3D) reconstruction of the dorsal and ventral pancreatic buds, in the human embryos, at Carnegie stages 15-23. The early development of the pancreas is studied by tissue observation and reconstruction by a computer-assisted method, using a light micrograph images from consecutive serial sagittal sections (diameter 7 microm) of ten human embryos ranging from Carnegie stages 15-23, CRL 7-27 mm, fixed, dehydrated and embedded in paraffin, were stained alternately with haematoxylin-eosin or Heindenhain'Azan. The images were digitalized by Canon Camera 350 EOS D. The serial views were aligned automatically by software, manual alignment was performed, the data were analysed following segmentation and threshold. The two buds were clearly identified at stage 15. In stage 16, both pancreatic buds were in final position, and begin to merge in stage 17. From stage 18 to the stage 23, surrounding connective tissue differentiated. In the stage 23, the morphology of the pancreas was definitive. The superior portion of the anterior face of the pancreas's head was arising from the dorsal bud. The rest of the head including the uncinate process emanated from the ventral bud. The 3D computer-assisted reconstruction of the human pancreas visualized the relationships between the two pancreatic buds. This explains the disposition and the modality of the components fusion. This embryologic development permits a better understanding of congenital abnormalities.

Evaluation of real time ultrasonography of the normal pancreas

International Nuclear Information System (INIS)

Kim, H. K.; Ko, Y. T.; Kim, S. Y.; Ahn, C. Y.

1981-01-01

91 cases who were free of pancreatic disease and the related conditions, were studied by high resolution and wide field real time ultrasonographic scanner with 3.5 MHz linear array electronically focusing transducers. The pancreatic examination method and the anatomic structures in and around the pancreas were investigated, and the normal pancreatic findings by real time ultrasonography were as follows: 1. Among all 91 cases, 44 cases were male and 47 cases female, and the frequent age groups were the 4th to the sixth decade. 2. The pancreatic images were obtained in 86% and the good images in 65%. 3. The shapes of pancreas were sausage (40%), dumb-bell (34%), tadpole (9%), and club (17%). 4. Pancreatic size was 1.56 ± 0.37, 2.4, 0.8 cm (Mean ± SD, Max., Min.) in head, 1.32 ± 0.29, 2.0, 0.8 cm in isthmus, and 1.62 ± 0.31, 2.4, 1.0 cm in tail. 5. The successful rate of pancreatic duct visualization was 46%. The shapes of pancreatic duct were linear (22%), tramline (16%), and tubular (8%). 6. The pancreatic echogenecity is greater than that of the liver in 68%, and equivalent to that of the liver in 32%, and no normal pancreas displayed less echogenecity than the liver. 7. Pancreatic echogenecity is lesser than that of adjacent soft tissue in 79% and equivalent to that of adjacent soft tissue in 21%. 8. The pancreatic echogenecity is homogenous in 79%. 9. The pancreatic margin is smooth in 62%, undulated in 11%, and ill defined in 27%

Presence of Human Herpesvirus 6B in the Pancreas of Subjects With and Without Type 1 Diabetes.

Science.gov (United States)

Ericsson, Maja; Skog, Oskar

The aims of this study were to investigate the presence of human herpesvirus 6 (HHV6) A and B in human pancreata and to search for signs of active infection in this organ of subjects with and without type 1 diabetes (T1D). Pancreata from brain-dead organ donors with and without T1D were examined for the presence of HHV6 genomic sequences by polymerase chain reaction (PCR), transcripts by reverse transcriptase-PCR, and protein by immunohistochemistry. Quantitative PCR of isolated pancreatic islets and exocrine cell clusters was used to determine the intrapancreatic location of HHV6 DNA. Human herpesvirus 6B genomic sequences were present in 1 of 2 donors who died of acute-onset T1D, 4 of 6 donors with long-standing T1D, and 9 of 12 nondiabetic donors. Higher copy numbers of HHV6B DNA were present in isolated islets than in exocrine tissue from the same donors. No signs of active HHV6 transcription were found. Human herpesvirus 6A was not present in any tested pancreas. The herein presented data demonstrate, for the first time, the presence of a latent HHV6B infection in the pancreas and islets of Langerhans. Whether this virus can contribute to disease in the pancreas remains to be determined.

Developmental biology of the Psammomys obesus pancreas

DEFF Research Database (Denmark)

Vedtofte, Louise; Bödvarsdóttir, Thóra B; Karlsen, Allan E

2007-01-01

The desert gerbil Psammomys obesus, an established model of type 2 diabetes (T2D), has previously been shown to lack pancreatic and duodenal homeobox gene 1 (Pdx-1) expression. Pdx-1 deficiency leads to pancreas agenesis in both mice and humans. We have therefore further examined the pancreas of ...

Focal uptake of 68Ga-DOTATOC in the pancreas: pathological or physiological correlate in patients with neuroendocrine tumours?

International Nuclear Information System (INIS)

Al-Ibraheem, Akram; Bundschuh, Ralph Alexander; Notni, Johannes; Winter, Anna; Wester, Hans-Juergen; Schwaiger, Markus; Scheidhauer, Klemens; Buck, Andreas

2011-01-01

Neuroendocrine tumours are frequently located in the upper abdomen and especially in the pancreas. Imaging of the abdomen with somatostatin analogs such as 68 Ga-DOTA-Phe 1 -Tyr 3 -octreotide (DOTATOC) is a standard approach for imaging neuroendocrine cancer, but is still challenging due to physiological and technical considerations in this area. Therefore, the aim of this study was to further investigate the origin of 68 Ga-DOTATOC findings in the pancreas. Forty-three consecutive patients with neuroendocrine tumours were examined by 68 Ga-DOTATOC positron emission tomography (PET)/CT for staging or restaging. As imaging of the upper abdomen is frequently affected by breathing artefacts, PET and CT data were analysed for misalignment and rearranged if necessary. Any noticeable uptake in the pancreas was described. Tracer uptake in the head of the pancreas and the liver was measured by means of maximum and average standard uptake value (SUV max , SUV av ). The reference standards (malignant versus benign) for correlation with PET findings were clinical and radiological follow-up (mean follow-up time 14 months) (n = 37) or histological confirmation (n = 6). In 23 of 43 studies (54%) misalignment between PET and CT data was found with a mean value of 1.4 cm. Visual assessment demonstrated that 20 of 43 scans (46.6%) showed no uptake in the head of the pancreas. Of 43 scans, 23 (53.4%) showed noticeable uptake with focal pattern in the head of the pancreas in 10 scans and irregular pattern in 13 scans. Follow-up indicated malignant pancreatic lesions in three patients. The pancreatic head to liver SUV av ratios in these patients ranged from 1.62 to 6.85, whereas in cases of uptake without known malignancy ratios ranged from 0.56 to 1.19. Considering SUV max , the ratio ranged from 3.24 to 9.1 and from 0.84 to 1.47, respectively. No statistically significant difference was noted between uptake in the head of the pancreas and the liver in patients without malignant

Radioisotope Scanning of the Pancreas with Selenomethionine-Se{sup 75}; Gammagraphie du Pancreas a l'Aide de la Selenomethionine-{sup 75}Se; Diagnosticheskoe fotoskennirovanie podzheludochnoj zhelezy; Gammagrafia del Pancreas Mediante Radioisotopos

Energy Technology Data Exchange (ETDEWEB)

Sodee, D. B. [Doctors Hospital and Renner Clinic Foundation, Cleveland Heights, OH (United States)

1964-10-15

Photoscanning of the pancreas utilizing selenomethionine- Se{sup 75} has recently been shown to be a practical technique. In a series of 100 patients who underwent 250 such photoscans, the pancreas was visualized in 90% of the cases. The physiological stimulation of the pancreas was found to be the most important factor in pancreatic selenomethionine-Se{sup 75} concentration. Utilizing a 30-g protein meal, physiological stimulation of the pancreas was begun one hour before the intravenous administration of 3 to 4- {mu}c/kg selenomethionine-Se{sup 75}. Fifteen minutes later continued stimulation of the pancreas was ensured by the oral administration of 900 {mu}g of glutamic acid hydrochloride. Before scanning the pancreas, a 3/8 - in curved lead shield was placed over the liver bed previously outlined by an Au{sup 198} liver scan. This lead shield blocks the radiation from the concentration of selenomethionine-Se{sup 75} in the liver that in the past impaired accurate delineation of the pancreas. The authors have recently utilized a 5-in by 3-in crystal and a 121-hole lead collimator with a 5-in focal distance. This has further improved delineation of the pancreas and, as the technique is perfected, smaller lesions at greater depths may be visualized. The results show that pancreatic carcinoma does not concentrate selenomethionine-Se{sup 75} as well as normal tissue. Five of six patients with pancreatic carcinoma had their disease correctly interpreted by this procedure. The smallest carcinoma not visualized was obscured by an enlarged liver. Acute and chronic pancreatitis are also confirmed by the pancreatic scan as the impaired cells of the pancreas do not concentrate selenomethionine-Se{sup 75}. The author also reports selective uptake of selenomethionine-Se{sup 75} by parathyroid tissue. Utilizing the. same scanning technique parathyroid adenomas in a small group of hyperparathyroid patients have been visualized. Photoscanning of the pancreas is already a

In vitro metabolism of [14C]-toluene by human and rat liver microsomes and liver slices

International Nuclear Information System (INIS)

Chapman, D.E.; Moore, T.J.; Michener, S.R.; Powis, G.

1990-01-01

Toluene metabolites produced by liver microsomes from six human donors included benzylalcohol (Balc), benzaldehyde (Bald) and benzoic acid (Bacid). Microsomes from only one human donor metabolized toluene to p-cresol and o-cresol. Human liver microsomes also metabolized Balc to Bald. Balc metabolism required NADPH, was inhibited by carbon monoxide, and was decreased at a buffer pH of 10. Balc metabolism was not inhibited by ADP-ribose or sodium azide. These results suggest that cytochrome P450 is responsible for the in vitro metabolism of Balc by human liver microsomes. Toluene metabolites formed by human liver slices and released into the incubation media included hippuric acid, and Bacid. Cresols or cresol-conjugates were not detected in liver slice incubation media from any human donor. Toluene metabolism by human liver was compared to metabolism by comparable liver preparations from male Fischer F344 rats. Rates of toluene metabolism by human liver microsomes and liver slices were 9-fold and 1.3-fold greater than for rat liver, respectively. Covalent binding of toluene to human liver microsomes and liver slices was 21-fold and 4-fold greater than for comparable rat liver preparations. Covalent binding of toluene to human microsomes required NADPH, was significantly decreased by coincubation with 4 mM cysteine or 4 mM glutathione, and radioactivity associated with microsomes was decreased by subsequent digestion of microsomes with protease. These results suggest that toluene metabolism and covalent binding of toluene are underestimated if the male Fischer 344 rat is used as a model for human toluene metabolism

Comparative Study of Human Liver Ferritin and Chicken Liver by Moessbauer Spectroscopy. Preliminary Results

Energy Technology Data Exchange (ETDEWEB)

Oshtrakh, M. I. [Ural State Technical University - UPI, Division of Applied Biophysics, Faculty of Physical Techniques and Devices for Quality Control (Russian Federation); Milder, O. B.; Semionkin, V. A. [Ural State Technical University - UPI, Faculty of Experimental Physics (Russian Federation); Prokopenko, P. G. [Russian State Medical University, Faculty of Biochemistry (Russian Federation); Malakheeva, L. I. [Simbio Holding, Science Consultation Department (Russian Federation)

2004-12-15

A comparative study of normal human liver ferritin and livers from normal chicken and chicken with Marek disease was made by Moessbauer spectroscopy. Small differences of quadrupole splitting and isomer shift were found for human liver ferritin and chicken liver. Moessbauer parameters for liver from normal chicken and chicken with Marek disease were the same.

Comparative Study of Human Liver Ferritin and Chicken Liver by Moessbauer Spectroscopy. Preliminary Results

International Nuclear Information System (INIS)

Oshtrakh, M. I.; Milder, O. B.; Semionkin, V. A.; Prokopenko, P. G.; Malakheeva, L. I.

2004-01-01

A comparative study of normal human liver ferritin and livers from normal chicken and chicken with Marek disease was made by Moessbauer spectroscopy. Small differences of quadrupole splitting and isomer shift were found for human liver ferritin and chicken liver. Moessbauer parameters for liver from normal chicken and chicken with Marek disease were the same.

Activation and amplification of c-Ki-ras in a chemically induced transplantable human pancreas carcinoma

International Nuclear Information System (INIS)

Parsa, I.; Maheshwari, K.K.

1986-01-01

Increasing evidence suggests that carcinogenesis is associated with the stepwise activation of oncogenes. The c-Ki-ras oncogene has been demonstrated in several human solid tumors and is shown to be amplified in tumor cell lines. The authors have probed endonuclease cleaved human pancreas (HP) DNAs and DNAs from an in vitro induced transplantable human pancreas carcinoma (HP-T1) for the presence and/or amplification of c-Ki-ras oncogene. The DNAs were cleaved with BamHI, BgIII, EcoRI, HhaI, HinfI, KpnI, PSTI, PvuII, SaII, SstI, TaqI or XbaI and were subjected to Southern blot analysis using 32 P-labelled EcoRI fragments from HiHi3 clone. The hybridization profiles were similar in both DNAs when digested with BamHI, BgIII, HinfI, KpnI, SaII, SstI, or TaqI. The EcoRI cleaved DNAs from HP and HP-T1 revealed two hybridizing fragments of 6.8 and 3.0 kbp. The 3.0 kbp fragments in DNA from HP-T1 showed more than a 100 folds enhancement as compared to that of HP. The 6.8 hybridizing fragments also appeared 10 fold greater in HP-T1 DNA. Similar enhancements were also present in HP-T1 DNA cleaved with PstI and PvuII. Preliminary results from comparison of poly(A) + RNAs, prepared from total HP and HP-T1 RNAs, by Northern blot analysis using the same probe reflect similar enhancement in RNA from transplantable pancreas carcinoma

HUMAN LIVER SLICES EXPRESS THE SAME LIDOCAINE BIOTRANSFORMATION RATE AS ISOLATED HUMAN HEPATOCYTES

NARCIS (Netherlands)

OLINGA, P; MEIJER, DKF; SLOOFF, MJH; GROOTHUIS, GMM; Merema, M.T.

1993-01-01

In order to investigate whether liver slices are a valuable tool for the assessment of drug metabolism in human liver, we compared the phase I metabolism of lidocaine in human liver slices and hepatocytes prepared from three human livers. Lidocaine is mainly metabolised to monoethylglycinexylidide

Pancreas Transplantation

Science.gov (United States)

The pancreas is a gland behind your stomach and in front of your spine. It produces the juices that ... hormones that help control blood sugar levels. A pancreas transplant is surgery to place a healthy pancreas ...

MicroRNA Dysregulation in Liver and Pancreas of CMP-Neu5Ac Hydroxylase Null Mice Disrupts Insulin/PI3K-AKT Signaling

Directory of Open Access Journals (Sweden)

Deug-Nam Kwon

2014-01-01

Full Text Available CMP-Neu5Ac hydroxylase (Cmah-null mice fed with a high-fat diet develop fasting hyperglycemia, glucose intolerance, and pancreatic β-cell dysfunction and ultimately develop characteristics of type 2 diabetes. The precise metabolic role of the Cmah gene remains poorly understood. This study was designed to investigate the molecular mechanisms through which microRNAs (miRNAs regulate type 2 diabetes. Expression profiles of miRNAs in Cmah-null mouse livers were compared to those of control mouse livers. Liver miFinder miRNA PCR arrays (n=6 showed that eight miRNA genes were differentially expressed between the two groups. Compared with controls, seven miRNAs were upregulated and one miRNA was downregulated in Cmah-null mice. Specifically, miR-155-5p, miR-425-5p, miR-15a-5p, miR-503-5p, miR-16-5p, miR-29a-3p, and miR-29b-3p were significantly upregulated in the liver and pancreas of Cmah-null mice. These target miRNAs are closely associated with dysregulation of insulin/PI3K-AKT signaling, suggesting that the Cmah-null mice could be a useful model for studying diabetes.

Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman.

Science.gov (United States)

Lestelle, Valentin; de Coster, Claire; Sarran, Anthony; Poizat, Flora; Delpero, Jean-Robert; Raoul, Jean-Luc

2015-01-01

We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare.

What Is the Pancreas?

Science.gov (United States)

... Pancreas Function of the Pancreas What is the pancreas? The pancreas is a long flattened gland located ... controller of blood sugar levels. Where is the pancreas? The pancreas is located deep in the abdomen. ...

Volumetric gain of the human pancreas after left partial pancreatic resection: A CT-scan based retrospective study.

Science.gov (United States)

Phillip, Veit; Zahel, Tina; Danninger, Assiye; Erkan, Mert; Dobritz, Martin; Steiner, Jörg M; Kleeff, Jörg; Schmid, Roland M; Algül, Hana

2015-01-01

Regeneration of the pancreas has been well characterized in animal models. However, there are conflicting data on the regenerative capacity of the human pancreas. The aim of the present study was to assess the regenerative capacity of the human pancreas. In a retrospective study, data from patients undergoing left partial pancreatic resection at a single center were eligible for inclusion (n = 185). Volumetry was performed based on 5 mm CT-scans acquired through a 256-slice CT-scanner using a semi-automated software. Data from 24 patients (15 males/9 females) were included. Mean ± SD age was 68 ± 11 years (range, 40-85 years). Median time between surgery and the 1st postoperative CT was 9 days (range, 0-27 days; IQR, 7-13), 55 days (range, 21-141 days; IQR, 34-105) until the 2nd CT, and 191 days (range, 62-1902; IQR, 156-347) until the 3rd CT. The pancreatic volumes differed significantly between the first and the second postoperative CT scans (median volume 25.6 mL and 30.6 mL, respectively; p = 0.008) and had significantly increased further by the 3rd CT scan (median volume 37.9 mL; p = 0.001 for comparison with 1st CT scan and p = 0.003 for comparison with 2nd CT scan). The human pancreas shows a measurable and considerable potential of volumetric gain after partial resection. Multidetector-CT based semi-automated volume analysis is a feasible method for follow-up of the volume of the remaining pancreatic parenchyma after partial pancreatectomy. Effects on exocrine and endocrine pancreatic function have to be evaluated in a prospective manner. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Fraction from human and rat liver which is inhibitory for proliferation of liver cells.

Science.gov (United States)

Chen, T S; Ottenweller, J; Luke, A; Santos, S; Keeting, P; Cuy, R; Lea, M A

1989-01-01

A comparative study was undertaken with human and rat liver of a fraction reported to have growth inhibitory activity when prepared from rat liver. Fractions which were soluble in 70% ethanol and insoluble in 87% ethanol were prepared from liver cytosols. Electrophoretic analysis under denaturing conditions indicated that there were several quantitative or qualitative differences in the fractions from the two species. Fractions from both human and rat liver were found to be inhibitory for the incorporation of 3H-thymidine into DNA of foetal chick hepatocytes. Under conditions in which the rat fraction inhibited precursor incorporation into DNA of rat liver epithelial cells there was not a significant inhibitory effect with the fraction from human liver. DNA synthesis in a rat hepatoma cell line was not significantly inhibited by preparations from either species. The data suggested that corresponding fractions from both rat and human liver could have inhibitory effects on precursor incorporation into DNA but the magnitude of the effects and target cell specificity may differ.

Regional differences in islet distribution in the human pancreas--preferential beta-cell loss in the head region in patients with type 2 diabetes.

Directory of Open Access Journals (Sweden)

Xiaojun Wang

Full Text Available While regional heterogeneity in islet distribution has been well studied in rodents, less is known about human pancreatic histology. To fill gaps in our understanding, regional differences in the adult human pancreas were quantitatively analyzed including the pathogenesis of type 2 diabetes (T2D. Cadaveric pancreas specimens were collected from the head, body and tail regions of each donor, including subjects with no history of diabetes or pancreatic diseases (n = 23 as well as patients with T2D (n = 12. The study further included individuals from whom islets were isolated (n = 7 to study islet yield and function in a clinical setting of islet transplantation. The whole pancreatic sections were examined using an innovative large-scale image capture and unbiased detailed quantitative analyses of the characteristics of islets from each individual (architecture, size, shape and distribution. Islet distribution/density is similar between the head and body regions, but is >2-fold higher in the tail region. In contrast to rodents, islet cellular composition and architecture were similar throughout the pancreas and there was no difference in glucose-stimulated insulin secretion in islets isolated from different regions of the pancreas. Further studies revealed preferential loss of large islets in the head region in patients with T2D. The present study has demonstrated distinct characteristics of the human pancreas, which should provide a baseline for the future studies integrating existing research in the field and helping to advance bi-directional research between humans and preclinical models.

Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman

Directory of Open Access Journals (Sweden)

Valentin Lestelle

2015-10-01

Full Text Available We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare.

Endoscopic Ultrasound Elastography: Current Clinical Use in Pancreas.

Science.gov (United States)

Mondal, Utpal; Henkes, Nichole; Patel, Sandeep; Rosenkranz, Laura

2016-08-01

Elastography is a newer technique for the assessment of tissue elasticity using ultrasound. Cancerous tissue is known to be stiffer (hence, less elastic) than corresponding healthy tissue, and as a result, could be identified in an elasticity-based imaging. Ultrasound elastography has been used in the breast, thyroid, and cervix to differentiate malignant from benign neoplasms and to guide or avoid unnecessary biopsies. In the liver, elastography has enabled a noninvasive and reliable estimate of fibrosis. Endoscopic ultrasound has become a robust diagnostic and therapeutic tool for the management of pancreatic diseases. The addition of elastography to endoscopic ultrasound enabled further characterization of pancreas lesions, and several European and Asian studies have reported encouraging results. The current clinical role of endoscopic ultrasound elastography in the management of pancreas disorders and related literature are reviewed.

Isolation of primary human hepatocytes from normal and diseased liver tissue: a one hundred liver experience.

Directory of Open Access Journals (Sweden)

Ricky H Bhogal

2011-03-01

Full Text Available Successful and consistent isolation of primary human hepatocytes remains a challenge for both cell-based therapeutics/transplantation and laboratory research. Several centres around the world have extensive experience in the isolation of human hepatocytes from non-diseased livers obtained from donor liver surplus to surgical requirement or at hepatic resection for tumours. These livers are an important but limited source of cells for therapy or research. The capacity to isolate cells from diseased liver tissue removed at transplantation would substantially increase availability of cells for research. However no studies comparing the outcome of human hepatocytes isolation from diseased and non-diseased livers presently exist. Here we report our experience isolating human hepatocytes from organ donors, non-diseased resected liver and cirrhotic tissue. We report the cell yields and functional qualities of cells isolated from the different types of liver and demonstrate that a single rigorous protocol allows the routine harvest of good quality primary hepatocytes from the most commonly accessible human liver tissue samples.

Design of a bioartificial pancreas

Science.gov (United States)

Pareta, Rajesh A; Farney, Alan C; Opara, Emmanuel C

2013-01-01

Summary Islet transplantation has been shown to be a viable treatment option for patients afflicted with Type 1 diabetes. However, the severe shortage of human pancreas and the need to use risky immunosuppressive drugs to prevent transplant rejection remain two major obstacles to routine use of islet transplantation in diabetic patients. Successful development of a bioartificial pancreas using the approach of microencapsulation with perm-selective coating of islets in hydrogels for graft immunoisolation holds tremendous promise for diabetic patients because it has great potential to overcome these two barriers. In this review article, we will discuss the need for bioartificial pancreas, provide a detailed description of the microencapsulation process, and review the status of the technology in clinical development. We will also critically review the various factors that need to be taken into consideration in order to achieve the ultimate goal of routine clinical application. PMID:23652283

Studies on the relationship between computed tomography of pancreas and ages or body constitution

International Nuclear Information System (INIS)

Katsumata, Kazuo; Katsumata, Yoshinao; Nakagawa, Takeo; Sakuma, Sadayuki.

1984-01-01

We have clarified that computed tomography of pancreas can be divided into three types each in margin and content, namely 1) smooth type 2) fine-granule type 3) rough-granule type. In rough-granule type, rough granules are surrounded by low density area whose CT value is around -80. This CT value suggests that in rough-granule type, large amount of lipid may be present in pancreas. In this report, pancreatic CT scan of 406 persons without gall stone, diabetes mellitus, liver cirrhosis, pancreatitis and malignant tumor were studied. Incidence of the rough-granule type was very low in lean persons, while that of the rough-granule type was high in obese persons. Present results indicate that these types of pancreas in CT scan has intimate relation to body constitution. We discussed the clinical significance of this classification of pancreatic CT scan in relation to lipid deposition in pancreas. (author)

Studies on the relationship between computed tomography of pancreas and ages or body constitution

Energy Technology Data Exchange (ETDEWEB)

Katsumata, Kazuo; Katsumata, Yoshinao; Nakagawa, Takeo; Sakuma, Sadayuki

1984-12-01

We have clarified that computed tomography of pancreas can be divided into three types each in margin and content, namely 1) smooth type 2) fine-granule type 3) rough-granule type. In rough-granule type, rough granules are surrounded by low density area whose CT value is around -80. This CT value suggests that in rough-granule type, large amount of lipid may be present in pancreas. In this report, pancreatic CT scan of 406 persons without gall stone, diabetes mellitus, liver cirrhosis, pancreatitis and malignant tumor were studied. Incidence of the rough-granule type was very low in lean persons, while that of the rough-granule type was high in obese persons. Present results indicate that these types of pancreas in CT scan has intimate relation to body constitution. We discussed the clinical significance of this classification of pancreatic CT scan in relation to lipid deposition in pancreas. (author).

SU-E-J-168: Automated Pancreas Segmentation Based On Dynamic MRI

International Nuclear Information System (INIS)

Gou, S; Rapacchi, S; Hu, P; Sheng, K

2014-01-01

Purpose: MRI guided radiotherapy is particularly attractive for abdominal targets with low CT contrast. To fully utilize this modality for pancreas tracking, automated segmentation tools are needed. A hybrid gradient, region growth and shape constraint (hGReS) method to segment 2D upper abdominal dynamic MRI is developed for this purpose. Methods: 2D coronal dynamic MR images of 2 healthy volunteers were acquired with a frame rate of 5 f/second. The regions of interest (ROIs) included the liver, pancreas and stomach. The first frame was used as the source where the centers of the ROIs were annotated. These center locations were propagated to the next dynamic MRI frame. 4-neighborhood region transfer growth was performed from these initial seeds for rough segmentation. To improve the results, gradient, edge and shape constraints were applied to the ROIs before final refinement using morphological operations. Results from hGReS and 3 other automated segmentation methods using edge detection, region growth and level set were compared to manual contouring. Results: For the first patient, hGReS resulted in the organ segmentation accuracy as measure by the Dices index (0.77) for the pancreas. The accuracy was slightly superior to the level set method (0.72), and both are significantly more accurate than the edge detection (0.53) and region growth methods (0.42). For the second healthy volunteer, hGReS reliably segmented the pancreatic region, achieving a Dices index of 0.82, 0.92 and 0.93 for the pancreas, stomach and liver, respectively, comparing to manual segmentation. Motion trajectories derived from the hGReS, level set and manual segmentation methods showed high correlation to respiratory motion calculated using a lung blood vessel as the reference while the other two methods showed substantial motion tracking errors. hGReS was 10 times faster than level set. Conclusion: We have shown the feasibility of automated segmentation of the pancreas anatomy based on

Radiological evaluation of a liver simulator in comparison to a human real liver

International Nuclear Information System (INIS)

Toledo, Janine M.; Campos, Tarcisio P.R. de

2009-01-01

The present study evaluates the radiological features of a human real healthy liver reproducing its characteristics on a developed liver simulator. The radiological evaluation will be performed through radiological methods such as CT and X-ray images, density and weight measurements, as well as representation of the coloration and texture. According to literature, the liver is the highest weight organ and gland of the body, weighing approximately 1,5 kg. On the liver, the nutrients are absorbed from the digestive tract and are prosecuted and stored for future use by other organs. Also the liver is responsible for the neutralization and elimination of various toxic substances. Thus, it is an interface between the digestive system and the blood. Besides, this organ is the principal source of plasmatic proteins like the albumin, transport of graxos oily acids. Due to its proprieties, the liver holds a large amount of radionuclides on any uptake from external source. The liver simulator was designed to have the same density, weight and corresponding shape. The radiographic image was produced by conventional X-rays machine, in which the radiographic applied parameters were the same applied to abdomen. The result of the radiographic and CT images demonstrates radiological equivalence between the simulator and human real liver. Hounsfield number of the synthetic liver tissue was found on the range of human livers. Therefore, due to its similar shape, chemical composition, radiological response, the liver simulator can be used to investigate ionizing radiation procedures during radiation therapy intervention. (author)

Dissection of the Mouse Pancreas for Histological Analysis and Metabolic Profiling.

Science.gov (United States)

Veite-Schmahl, Michelle J; Regan, Daniel P; Rivers, Adam C; Nowatzke, Joseph F; Kennedy, Michael A

2017-08-19

We have been investigating the pancreas specific transcription factor, 1a cre-recombinase; lox-stop-lox- Kristen rat sarcoma, glycine to aspartic acid at the 12 codon (Ptf1a cre/+ ;LSL-Kras G12D/+ ) mouse strain as a model of human pancreatic cancer. The goal of our current studies is to identify novel metabolic biomarkers of pancreatic cancer progression. We have performed metabolic profiling of urine, feces, blood, and pancreas tissue extracts, as well as histological analyses of the pancreas to stage the cancer progression. The mouse pancreas is not a well-defined solid organ like in humans, but rather is a diffusely distributed soft tissue that is not easily identified by individuals unfamiliar with mouse internal anatomy or by individuals that have little or no experience performing mouse organ dissections. The purpose of this article is to provide a detailed step-wise visual demonstration to guide novices in the removal of the mouse pancreas by dissection. This article should be especially valuable to students and investigators new to research that requires harvesting of the mouse pancreas by dissection for metabolic profiling or histological analyses.

Agenesis of the dorsal pancreas

Science.gov (United States)

Schnedl, Wolfgang J; Piswanger-Soelkner, Claudia; Wallner, Sandra J; Krause, Robert; Lipp, Rainer W

2009-01-01

During the last 100 years in medical literature, there are only 54 reports, including the report of Pasaoglu et al (World J Gastroenterol 2008; 14: 2915-2916), with clinical descriptions of agenesis of the dorsal pancreas in humans. Agenesis of the dorsal pancreas, a rare congenital pancreatic malformation, is associated with some other medical conditions such as hyperglycemia, abdominal pain, pancreatitis and a few other diseases. In approximately 50% of reported patients with this congenital malformation, hyperglycemia was demonstrated. Evaluation of hyperglycemia and diabetes mellitus in all patients with agenesis of the dorsal pancreas including description of fasting blood glucose, oral glucose tolerance test, glycated hemoglobin and medical treatment would be a future goal. Since autosomal dominant transmission has been suggested in single families, more family studies including imaging technologies with demonstration of the pancreatic duct system are needed for evaluation of this disease. With this letter to the editor, we aim to increase available information for the better understanding of this rare disease. PMID:19140241

Normal Pancreas Anatomy

Science.gov (United States)

... hyphen, e.g. -historical Searches are case-insensitive Pancreas Anatomy Add to My Pictures View /Download : Small: ... 1586x1534 View Download Large: 3172x3068 View Download Title: Pancreas Anatomy Description: Anatomy of the pancreas; drawing shows ...

Annular pancreas

Science.gov (United States)

... page: //medlineplus.gov/ency/article/001142.htm Annular pancreas To use the sharing features on this page, please enable JavaScript. An annular pancreas is a ring of pancreatic tissue that encircles ...

Biobanking of human pancreas cancer tissue: impact of ex-vivo procurement times on RNA quality.

Science.gov (United States)

Rudloff, Udo; Bhanot, Umesh; Gerald, William; Klimstra, David S; Jarnagin, William R; Brennan, Murray F; Allen, Peter J

2010-08-01

Tissue banking has become a major initiative at many oncology centers. The influence of warm ex-vivo ischemia times, storage times, and biobanking protocols on RNA integrity and subsequent microarray data is not well documented. A prospective institutional review board-approved protocol for the banking of abdominal neoplasms was initiated at Memorial Sloan-Kettering Cancer Center in 2001. Sixty-four representative pancreas cancer specimens snap-frozen at various ex-vivo procurement times (1 h) and banked during three time periods (2001-2004, 2004-2006, 2006-2008) were processed. RNA integrity was determined by microcapillary electrophoresis using the RNA integrity number (RIN) algorithm and by results of laser-capture microdissection (LCM). Overall, 42% of human pancreas cancer specimens banked under a dedicated protocol yielded RNA with a RIN of > or =7. Limited warm ex-vivo ischemia times did not negatively impact RNA quality (percentage of tissue with total RNA with RIN of > or =7 for 60 min, 42%), and long-term storage of banked pancreas cancer biospecimens did not negatively influence RNA quality (total RNA with RIN of > or =7 banked 2001-2004, 44%; 2004-2006, 38%; 2006-2008, 50%). RNA retrieved from pancreatic cancer samples with RIN of > or =7 subject to LCM yielded RNA suitable for further downstream applications. Fresh-frozen pancreas tissue banked within a standardized research protocol yields high-quality RNA in approximately 50% of specimens and can be used for enrichment by LCM. Quality of tissues of the biobank were not adversely impacted by limited variations of warm ischemia times or different storage periods. This study shows the challenges and investments required to initiate and maintain high-quality tissue repositories.

Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis

Science.gov (United States)

Xuan, Shouhong; Borok, Matthew J.; Decker, Kimberly J.; Battle, Michele A.; Duncan, Stephen A.; Hale, Michael A.; Macdonald, Raymond J.; Sussel, Lori

2012-01-01

Pancreatic agenesis is a human disorder caused by defects in pancreas development. To date, only a few genes have been linked to pancreatic agenesis in humans, with mutations in pancreatic and duodenal homeobox 1 (PDX1) and pancreas-specific transcription factor 1a (PTF1A) reported in only 5 families with described cases. Recently, mutations in GATA6 have been identified in a large percentage of human cases, and a GATA4 mutant allele has been implicated in a single case. In the mouse, Gata4 and Gata6 are expressed in several endoderm-derived tissues, including the pancreas. To analyze the functions of GATA4 and/or GATA6 during mouse pancreatic development, we generated pancreas-specific deletions of Gata4 and Gata6. Surprisingly, loss of either Gata4 or Gata6 in the pancreas resulted in only mild pancreatic defects, which resolved postnatally. However, simultaneous deletion of both Gata4 and Gata6 in the pancreas caused severe pancreatic agenesis due to disruption of pancreatic progenitor cell proliferation, defects in branching morphogenesis, and a subsequent failure to induce the differentiation of progenitor cells expressing carboxypeptidase A1 (CPA1) and neurogenin 3 (NEUROG3). These studies address the conserved and nonconserved mechanisms underlying GATA4 and GATA6 function during pancreas development and provide a new mouse model to characterize the underlying developmental defects associated with pancreatic agenesis. PMID:23006325

Potential use of point shear wave elastography for the pancreas: A single center prospective study

International Nuclear Information System (INIS)

Kawada, Natsuko; Tanaka, Sachiko; Uehara, Hiroyuki; Ohkawa, Kazuyoshi; Yamai, Takuo; Takada, Ryoji; Shiroeda, Hisakazu; Arisawa, Tomiyasu; Tomita, Yasuhiko

2014-01-01

Aim: Clinical use of point shear wave elastography for the liver has been established, however, few studies demonstrated its usefulness for the pancreas. A prospective study was conducted to clarify its feasibility for the pancreas and its usefulness for the identification of high risk group for pancreatic cancer. Patients and methods: Consecutive eighty-five patients underwent point shear wave elastography for the pancreas. The success rate of shear wave velocity (SWV) measurement, that is the number of successful measurements over total 10 measurements, was recorded. The SWV of the pancreas measured at non-tumorous area was compared between patients with and without pancreatic cancer. Factors associated with high SWV were determined by logistic regression model. Results: Sixty patients were included, of these 18 had pancreatic cancer. The success rate of 100% was achieved at the head, the body and the tail of the pancreas in 80%, 83%, and 68% of the patients, respectively. The success rate of ≥80% was achieved in 100%, 100%, and 96% of the patients, respectively. Although mean SWV of the pancreas harboring pancreatic cancer tended to be higher compared with that of the pancreas without cancer (1.51 ± 0.45 m/s vs 1.43 ± 0.28 m/s), they did not reach statistical significance. Multivariate analysis showed that increased amount of alcohol intake was associated with high SWV. Conclusion: The SWV of the pancreas was measured with excellent success rate. However, tendency of higher SWV obtained from the pancreas harboring pancreatic cancer needed to be further investigated

Simultaneous multi-slice echo planar diffusion weighted imaging of the liver and the pancreas: Optimization of signal-to-noise ratio and acquisition time and application to intravoxel incoherent motion analysis

Energy Technology Data Exchange (ETDEWEB)

Boss, Andreas, E-mail: andreas.boss@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich (Switzerland); Barth, Borna; Filli, Lukas; Kenkel, David; Wurnig, Moritz C. [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich (Switzerland); Piccirelli, Marco [Institute of Neuroradiology, University Hospital of Zurich (Switzerland); Reiner, Caecilia S. [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich (Switzerland)

2016-11-15

Purpose: To optimize and test a diffusion-weighted imaging (DWI) echo-planar imaging (EPI) sequence with simultaneous multi-slice (SMS) excitation in the liver and pancreas regarding acquisition time (TA), number of slices, signal-to-noise ratio (SNR), image quality (IQ), apparent diffusion coefficient (ADC) quantitation accuracy, and feasibility of intravoxel incoherent motion (IVIM) analysis. Materials and methods: Ten healthy volunteers underwent DWI of the upper abdomen at 3T. A SMS DWI sequence with CAIPIRINHA unaliasing technique (acceleration factors 2/3, denoted AF2/3) was compared to standard DWI-EPI (AF1). Four schemes were evaluated: (i) reducing TA, (ii) keeping TA identical with increasing number of averages, (iii) increasing number of slices with identical TA (iv) increasing number of b-values for IVIM. Acquisition schemes i-iii were evaluated qualitatively (reader score) and quantitatively (ADC values, SNR). Results: In scheme (i) no differences in SNR were observed (p = 0.321 − 0.038) with reduced TA (AF2 increase in SNR/time 75.6%, AF3 increase SNR/time 102.4%). No SNR improvement was obtained in scheme (ii). Increased SNR/time could be invested in acquisition of more and thinner slices or higher number of b-values. Image quality scores were stable for AF2 but decreased for AF3. Only for AF3, liver ADC values were systematically lower. Conclusion: SMS-DWI of the liver and pancreas provides substantially higher SNR/time, which either may be used for shorter scan time, higher slice resolution or IVIM measurements.

Simultaneous multi-slice echo planar diffusion weighted imaging of the liver and the pancreas: Optimization of signal-to-noise ratio and acquisition time and application to intravoxel incoherent motion analysis

International Nuclear Information System (INIS)

Boss, Andreas; Barth, Borna; Filli, Lukas; Kenkel, David; Wurnig, Moritz C.; Piccirelli, Marco; Reiner, Caecilia S.

2016-01-01

Purpose: To optimize and test a diffusion-weighted imaging (DWI) echo-planar imaging (EPI) sequence with simultaneous multi-slice (SMS) excitation in the liver and pancreas regarding acquisition time (TA), number of slices, signal-to-noise ratio (SNR), image quality (IQ), apparent diffusion coefficient (ADC) quantitation accuracy, and feasibility of intravoxel incoherent motion (IVIM) analysis. Materials and methods: Ten healthy volunteers underwent DWI of the upper abdomen at 3T. A SMS DWI sequence with CAIPIRINHA unaliasing technique (acceleration factors 2/3, denoted AF2/3) was compared to standard DWI-EPI (AF1). Four schemes were evaluated: (i) reducing TA, (ii) keeping TA identical with increasing number of averages, (iii) increasing number of slices with identical TA (iv) increasing number of b-values for IVIM. Acquisition schemes i-iii were evaluated qualitatively (reader score) and quantitatively (ADC values, SNR). Results: In scheme (i) no differences in SNR were observed (p = 0.321 − 0.038) with reduced TA (AF2 increase in SNR/time 75.6%, AF3 increase SNR/time 102.4%). No SNR improvement was obtained in scheme (ii). Increased SNR/time could be invested in acquisition of more and thinner slices or higher number of b-values. Image quality scores were stable for AF2 but decreased for AF3. Only for AF3, liver ADC values were systematically lower. Conclusion: SMS-DWI of the liver and pancreas provides substantially higher SNR/time, which either may be used for shorter scan time, higher slice resolution or IVIM measurements.

Temperature profiles of different cooling methods in porcine pancreas procurement.

Science.gov (United States)

Weegman, Bradley P; Suszynski, Thomas M; Scott, William E; Ferrer Fábrega, Joana; Avgoustiniatos, Efstathios S; Anazawa, Takayuki; O'Brien, Timothy D; Rizzari, Michael D; Karatzas, Theodore; Jie, Tun; Sutherland, David E R; Hering, Bernhard J; Papas, Klearchos K

2014-01-01

Porcine islet xenotransplantation is a promising alternative to human islet allotransplantation. Porcine pancreas cooling needs to be optimized to reduce the warm ischemia time (WIT) following donation after cardiac death, which is associated with poorer islet isolation outcomes. This study examines the effect of four different cooling Methods on core porcine pancreas temperature (n = 24) and histopathology (n = 16). All Methods involved surface cooling with crushed ice and chilled irrigation. Method A, which is the standard for porcine pancreas procurement, used only surface cooling. Method B involved an intravascular flush with cold solution through the pancreas arterial system. Method C involved an intraductal infusion with cold solution through the major pancreatic duct, and Method D combined all three cooling Methods. Surface cooling alone (Method A) gradually decreased core pancreas temperature to <10 °C after 30 min. Using an intravascular flush (Method B) improved cooling during the entire duration of procurement, but incorporating an intraductal infusion (Method C) rapidly reduced core temperature 15-20 °C within the first 2 min of cooling. Combining all methods (Method D) was the most effective at rapidly reducing temperature and providing sustained cooling throughout the duration of procurement, although the recorded WIT was not different between Methods (P = 0.36). Histological scores were different between the cooling Methods (P = 0.02) and the worst with Method A. There were differences in histological scores between Methods A and C (P = 0.02) and Methods A and D (P = 0.02), but not between Methods C and D (P = 0.95), which may highlight the importance of early cooling using an intraductal infusion. In conclusion, surface cooling alone cannot rapidly cool large (porcine or human) pancreata. Additional cooling with an intravascular flush and intraductal infusion results in improved core porcine pancreas temperature profiles during procurement and

Importance and Limitations of Scintigraphy of the Pancreas: Results of 200 Examinations involving Electronic Subtraction of the Image of the Liver; Interet et Limites de la Scintigraphie Pancreatique: Resultats de 200 Examens Pratiques avec Soustraction Electronique de l'Image du Foie

Energy Technology Data Exchange (ETDEWEB)

Blanquet, P.; Beck, C.; Pigneux, J.; Hecquet, M. F. [Hopital Saint-Andre, Unite de Recherches INSERM, Bordeaux (France)

1969-05-15

In the course of routine hospital practice, the authors carried out 200 scintigraphic scans of the pancreas with suppression of the image of the liver. The examinations were made with an Anger camera, used in conjunction with the integrating memory of a 4096-channel pulse analyser. With this arrangement it was possible to subtract the data provided by heavy colloids of {sup 198}Au taken up by the liver from data relating to {sup 75}Se-labelled selenomethionine incorporated by the liver or the pancreas. The technique used is simple and requires immobilization of the patient for about one hour. Its purpose is to give an image of the pancreas free from any superimposed image of the liver and also to provide information on the rate at which the labelled compound is stored in the gland. The dose absorbed by the pancreas is minimal, owing to the short length of time that the radioisotope remains within the gland. The dose received by the whole body is not negligible and therefore the number of examinations made on subjects with a clinically normal pancreas was limited to five. Although its principle is open to criticism, the subtraction technique gave completely satisfactory results in practice. Suppression of the liver image was not always complete but in all cases the image of the pancreas was sufficiently isolated to allow interpretation of it as a whole. It should, however, be noted that the zone of projection common to the two organs is often somewhat inhomogenous after subtraction has been effected. In subjects free from pancreatic disorders, the scintigram was in all cases normal. In the cases of confirmed chronic pancreatitis the picture is unequivocal. The tumours can manifest themselves in a variety of scintigraphic images, but the definition of the images may be regarded as satisfactory since in one case the scintigram showed up a tumorous formation estimated to measure 2 cm at that time. (author) [French] Les auteurs ont pratique, en routine hospitaliere, 200

Pancreas developing markers expressed on human mononucleated umbilical cord blood cells

International Nuclear Information System (INIS)

Pessina, A.; Eletti, B.; Croera, C.; Savalli, N.; Diodovich, C.; Gribaldo, L.

2004-01-01

Haematopoietic system represents the main source of haematopoietic stem cells and probably of multipotential adult progenitor cells and mesenchimal stem cells at first described as colony forming unit-fibroblast. Whereas there are many studies on the gene expression profile of the different precursors along their haematopoietic differentiation, few data (sometimes conflicting) have been reported about the phenotype of the cells (present in bone marrow and possibly in cord blood) able to differentiate into non-haematopoietic cells. As both postnatal bone marrow and umbilical cord blood contain nestin positive cells able to proliferate and differentiate into the main neural phenotype (neuron, astroglia and oligodendroglia) many authors considered nestin a neuroepithelial precursor marker that seems to be essential also in multipotential progenitor cells of pancreas present both in rat and in human pancreatic islets (called nestin positive islet derived progenitors). Although the importance of nestin in these cells appears to be evident, it remains yet to clarify the number and the sequential expression of the genes coding all the transcription factors essential for beta cells differentiation and therefore the conditions able to induce the expression of many important transcription factors genes such as isl-1, pax-4, pdx-1 and ngn-3. Among them pdx-1 is a gene essential for pancreas development which is able to control ngn-3 in activating the expression of other differentiation factors for endocrine cells. Here, we describe for the first time in human umbilical cord blood cells (UCB) the pattern of expression of a panel of markers (nestin, CK-8, CK-18) and transcription factors (Isl-1, Pdx-1, Pax-4, Ngn-3) considered important for beta cells differentiation. Our data demonstrate that UCB contains a cell population having a phenotype very similar to endocrine cell precursors in transition to beta cells

In Vitro-Produced Pancreas Organogenesis Models In Three Dimensions

DEFF Research Database (Denmark)

Greggio, Chiara; De Franceschi, Filippo; Grapin-Botton, Anne

2015-01-01

of miniature organs in a dish and are emerging for the pancreas, starting from embryonic progenitors and adult cells. This review focusses on the currently available systems and how these allow new types of questions to be addressed. We discuss the expected advancements including their potential to study human...... pancreas development and function as well as to develop diabetes models and therapeutic cells. Stem Cells 2014....

Effect of donor fasting on survival of pancreas and heart grafts after warm ischemia.

Science.gov (United States)

Nishihara, M; Sumimoto, R; Asahara, T; Fukuda, Y; Southard, J H; Dohi, K

1996-09-01

Livers from fasted animals are believed to be more vulnerable to ischemic injury than those from fed donors. However, we have recently shown the opposite: livers from fasted rats were more tolerant to ischemic injury. Indeed, the survival rate of 60 min warm ischemic damaged livers increased from 0 to 90% if donor rats were fasted for three days. In this study, we examined how donor fasting affects the outcome of pancreas and heart preservation. BN rats were used as both donors and recipients, and recipients of pancreatic grafts were rendered diabetic prior to transplantation. Pancreatic or heart grafts were subjected to 90 min or 25 min of warm ischemia and were transplanted into the right side of the necks of recipients rats. The viability rate of hearts transplanted from fed donors into fed recipients was only about 11% (1/9) after transplantation. However, the viability rate with fasted donors was 75% (6/8). The rate of successful pancreatic grafting from fed donors into fed recipients was 28.6% (2/7), and that from fasted donors to fed recipients was 41.7% (5/12). These results confirm that the nutritional status of the donor is an important factor in the outcome of not only liver, but also pancreas and heart preservation during transplantation, although the effect of fasting on pancreatic graft is marginal.

Artifical Pancreas

Science.gov (United States)

Fei, Jiangfeng

2013-03-01

In 2006, JDRF launched the Artificial Pancreas Project (APP) to accelerate the development of a commercially-viable artificial pancreas system to closely mimic the biological function of the pancreas individuals with insulin-dependent diabetes, particularly type 1 diabetes. By automating detection of blood sugar levels and delivery of insulin in response to those levels, an artificial pancreas has the potential to transform the lives of people with type 1 diabetes. The 6-step APP development pathway serves as JDRF's APP strategic funding plan and defines the priorities of product research and development. Each step in the plan represents incremental advances in automation beginning with devices that shut off insulin delivery to prevent episodes of low blood sugar and progressing ultimately to a fully automated ``closed loop'' system that maintains blood glucose at a target level without the need to bolus for meals or adjust for exercise.

Extracellular Matrix Molecular Remodeling in Human Liver Fibrosis Evolution.

Directory of Open Access Journals (Sweden)

Andrea Baiocchini

Full Text Available Chronic liver damage leads to pathological accumulation of ECM proteins (liver fibrosis. Comprehensive characterization of the human ECM molecular composition is essential for gaining insights into the mechanisms of liver disease. To date, studies of ECM remodeling in human liver diseases have been hampered by the unavailability of purified ECM. Here, we developed a decellularization method to purify ECM scaffolds from human liver tissues. Histological and electron microscopy analyses demonstrated that the ECM scaffolds, devoid of plasma and cellular components, preserved the three-dimensional ECM structure and zonal distribution of ECM components. This method has been then applied on 57 liver biopsies of HCV-infected patients at different stages of liver fibrosis according to METAVIR classification. Label-free nLC-MS/MS proteomics and computation biology were performed to analyze the ECM molecular composition in liver fibrosis progression, thus unveiling protein expression signatures specific for the HCV-related liver fibrotic stages. In particular, the ECM molecular composition of liver fibrosis was found to involve dynamic changes in matrix stiffness, flexibility and density related to the dysregulation of predominant collagen, elastic fibers and minor components with both structural and signaling properties. This study contributes to the understanding of the molecular bases underlying ECM remodeling in liver fibrosis and suggests new molecular targets for fibrolytic strategies.

Point mutation in activated c-Ha-ras gene of a chemically induced transplantable human pancreas carcinoma

International Nuclear Information System (INIS)

Maheshwari, K.K.; Parsa, I.

1986-01-01

The authors have reported a model of human pancreas carcinogenesis where repeated treatment with MNU of explants results in the development of transplantable carcinoma. This report compares the endonuclease digests of DNAs from normal human pancreas (HP) and MNU-induced transplantable tumor (HP-T1) analyzed with 32 P-labelled Ha-ras probe prepared from clone BS-9. The hybridization patterns of BamHI, BglII, EcoRI and HindIII digests of HP were significantly different from those of HP-T1. In EcoRI digests a 3.0 kb fragments of HP-T1 DNA hybridized with Ha-ras probe instead of a 4.3 kb fragments seen in HP DNA. The pattern for HindIII digests was similar to those of EcoRI. The BgIII digests of HP DNA revealed two hybridizing fragments of 8.0 and 4.3 kb whereas those of HP-T1 DNA fragments measured 8.5 and 4.0 kb. BamHI treated HP DNA showed only hybridizing fragments of 6.6 kb while the HP-T1 DNA showed to hybridizing fragments of 6.8 and 7.2 kb. The digested DNAs by HhaI, HinfI, KpnI, pstI, PvuII, SaII, SstI, TaqI and XbaI showed similar hybridization profiles. The point mutation in c-Ha-ras was examined in the HpaII and MspI double digests of both DNAs by 0.6 Kb SmaI fragments of pEJ. The hybridized fragments measured 412 and 355 bp in DNA digests from tumor and normal pancreas respectively

Deep convolutional networks for pancreas segmentation in CT imaging

Science.gov (United States)

Roth, Holger R.; Farag, Amal; Lu, Le; Turkbey, Evrim B.; Summers, Ronald M.

2015-03-01

Automatic organ segmentation is an important prerequisite for many computer-aided diagnosis systems. The high anatomical variability of organs in the abdomen, such as the pancreas, prevents many segmentation methods from achieving high accuracies when compared to state-of-the-art segmentation of organs like the liver, heart or kidneys. Recently, the availability of large annotated training sets and the accessibility of affordable parallel computing resources via GPUs have made it feasible for "deep learning" methods such as convolutional networks (ConvNets) to succeed in image classification tasks. These methods have the advantage that used classification features are trained directly from the imaging data. We present a fully-automated bottom-up method for pancreas segmentation in computed tomography (CT) images of the abdomen. The method is based on hierarchical coarse-to-fine classification of local image regions (superpixels). Superpixels are extracted from the abdominal region using Simple Linear Iterative Clustering (SLIC). An initial probability response map is generated, using patch-level confidences and a two-level cascade of random forest classifiers, from which superpixel regions with probabilities larger 0.5 are retained. These retained superpixels serve as a highly sensitive initial input of the pancreas and its surroundings to a ConvNet that samples a bounding box around each superpixel at different scales (and random non-rigid deformations at training time) in order to assign a more distinct probability of each superpixel region being pancreas or not. We evaluate our method on CT images of 82 patients (60 for training, 2 for validation, and 20 for testing). Using ConvNets we achieve maximum Dice scores of an average 68% +/- 10% (range, 43-80%) in testing. This shows promise for accurate pancreas segmentation, using a deep learning approach and compares favorably to state-of-the-art methods.

Acinar Cell Carcinoma of the Pancreas with Colon Involvement

Directory of Open Access Journals (Sweden)

Naoki Asayama

2014-01-01

Full Text Available We report a case of acinar cell carcinoma of the pancreas with colon involvement that was difficult to distinguish from primary colon cancer. A 60-year-old man was admitted with a 1-month history of diarrhea. Contrast-enhanced computed tomography (CT revealed a large tumor (10.6×11.6 cm at the splenic flexure of the colon. Colonoscopy showed completely round ulcerative lesions, and biopsy revealed poorly differentiated adenocarcinoma. Left hemicolectomy, resection of the jejunum and pancreas body and tail, and splenectomy were performed based on a diagnosis of descending colon cancer (cT4N0M0, stage IIB, and surgery was considered to be curative. Diagnosis was subsequently confirmed as moderately differentiated acinar cell carcinoma of the pancreas by immunohistochemical staining (pT3N0M0, stage IIA. Multiple liver metastases with portal thrombosis were found 8 weeks postoperatively. Despite combination chemotherapy with oral S-1 and gemcitabine, the patient died of hepatic failure with no effect of chemotherapy 14 weeks postoperatively. Correct diagnosis was difficult to determine preoperatively from the clinical, CT, and colonoscopy findings. Moreover, the disease was extremely aggressive even after curative resection. Physicians should consider pancreatic cancer in the differential diagnosis of similar cases.

Antimicrobial Peptide Human Neutrophil Peptide 1 as a Potential Link Between Chronic Inflammation and Ductal Adenocarcinoma of the Pancreas.

Science.gov (United States)

Pausch, Thomas; Adolph, Sarah; Felix, Klaus; Bauer, Andrea S; Bergmann, Frank; Werner, Jens; Hartwig, Werner

Defensins are antimicrobial peptides playing a role in innate immunity, in epithelial cell regeneration, and in carcinogenesis of inflammation-triggered malignancies. We analyzed this role in pancreatic ductal adenocarcinoma (PDAC) in the context of its association with chronic pancreatitis (CP). Human tissue of healthy pancreas, CP, and PDAC was screened for defensins by immunohistochemistry. Defensin α 1 (human neutrophil peptide 1 [HNP-1]) expression was validated using mass spectrometry and microarray analysis. Human neutrophil peptide 1 expression and influences of proinflammatory cytokines (tumor necrosis factor α, interleukin 1β, and interferon γ) were studied in human pancreatic cancer cells (Colo 357, T3M4, PANC-1) and normal human pancreatic duct epithelial cells (HPDE). Accumulation of HNP-1 in malignant pancreatic ductal epithelia was seen. Spectrometry showed increased expression of HNP-1 in CP and even more in PDAC. At RNA level, no significant regulation was found. In cancer cells, HNP-1 expression was significantly higher than in HPDE. Proinflammatory cytokines significantly led to increased HNP-1 levels in culture supernatants and decreased levels in lysates of cancer cells. In HPDE cytokines significantly decreased HNP-1 levels. Inflammatory regulation of HNP-1 in PDAC tissue and cells indicates that HNP-1 may be a link between chronic inflammation and malignant transformation in the pancreas.

Aggressive venous invasion in the area of carcinoma correlates with liver metastasis as an index of metastasis for invasive ductal carcinoma of the pancreas.

Science.gov (United States)

Hamada, Yoshihiro; Nakayama, Yoshifuku

Invasive ductal carcinoma of the pancreas (IDCP) predominantly causes death through liver metastasis (LM) and peritoneal dissemination with local recurrence. However, whether its venous invasion is from the enlarged carcinoma accompanied by tumor growth, or from a distinct carcinoma group, for which venous invasion is facilitated by proximity to the origin, is unclear. We analyzed the correlation between LM and venous invasion in patients with small IDCP tumors. Of 388 patients who were diagnosed with IDCP, 20 (5.2%) had tumors with diameters IDPC. Patients in whom ≥60% of veins were invaded by IDCP should be prepared for LM. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Malignant neoplasms of the pancreas, liver, and biliary tract

International Nuclear Information System (INIS)

Lawson, T.L.; Berland, L.L.; Foley, W.D.

1985-01-01

Ductal adenocarcinoma of the pancreas is of increasing medical importance in the United States. The age-adjusted mortality rate has risen from 2.9 to 9.0 per 100,000 population between the years 1920 and 1970. This represents an increase of over 300%. Since the mean survival from time of diagnosis is only 4.3 months, the mortality and incidence rates essentially are equal. Pancreatic carcinoma now accounts for 3% of all cancers and 5% of all cancer deaths in the United States. It is the fourth most common cause of death from cancer in men and the fifth most common in women. Despite advances in chemotherapy and radiation therapy, these modalities are primarily palliative and have not been shown to alter survival significantly

Pancreas cancer

International Nuclear Information System (INIS)

Yamada, Shigeru; Kato, Hirotoshi; Hara, Ryusuke

2006-01-01

Adenocarcinoma of the pancreas continues to be a significant source of cancer mortality in Japan, resulting in approximately 19,000 deaths a year. It is the fifth leading cause of cancer-related deaths in Japan, with a less than 5% 5-year expected survival rate. About 70-75% of patients with pancreas cancer present with locally advanced disease or distant metastases and have a median survival time of only 6 months. For unresectable pancreas cancer, the median survival time with external beam radiation (EBRT) was better than with surgical bypass or stents alone. The median survival of EBRT alone was 4 to 7 months. The median survival with combined EBRT and chemotherapy for locally unresectable tumor are 8 to 10 months and better than with the EBRT alone. Local failure of these combined therapies was still 26 to 48%. On the other hand, surgery with curative intent is undertaken in 15-20% of patients. Even after resection, the predicted 5-year survival rates are still less than 20%. Local recurrences in the pancreatic bed are seen in 50% of the patients undergoing presumed curative resection. We examined the effect of carbon ion therapy in terms of reducing the rate of local recurrence in patients with locally advanced adenocarcinoma of the pancreas or undergoing resection for adenocarcinoma of the pancreas. (author)

Enhancement of the normal pancreas: comparison of manganese-DPDP and gadolinium chelate

International Nuclear Information System (INIS)

Kettritz, U.; Warshauer, D.M.; Brown, E.D.; Schlund, J.F.; Eisenberg, L.B.; Semelka, R.C.

1996-01-01

The purpose of this paper was to compare manganese-DPDP (Mn-DPDP) and gadolinium chelate (Gd-DTPA) contrast agents for enhancement of the normal pancreas. A total of 14 patients with focal liver disease underwent Mn-DPDP-and Gd-DTPA-enhanced 1.5 T MR examinations using spoiled gradient-echo (FLASH) technique at two separate times. Contrast agents were injected according to the currently recommended practices; Gd-DTPA was injected as a rapid bolus injection in a dosage of 0.1 mmol/kg, and Mn-DPDP was injected as a slow IV injection in a dosage of 5 μmol/kg. Quantitative region of interest measurements were made in 11 patients, and percent contrast enhancement of the pancreas and pancreas-fat signal-to-noise ratios (SNR) were determined for each agent. Images were also evaluated qualitativley by consensus reading of two investigators and overall scan quality was rated on a scale from 1 (poor) to 4 (very good). Enhancement of the pancreas immediately post Gd-DTPA was significantly higher than 15 min post Mn-DPDP (73.3 vs 36.3%; p=0.003). On postcontrast images the pancreas-fat SNR measruements were 7.7 (i.e., pancreas higher in signal than fat) and -6.1 for Gd-DTPA and Mn-DPDP, respectively, which was significantly different (p<0.001). Image quality was rated as 3.1 and 2.5 for Gd-DTPA- and Mn-DPDP-enhanced images, respectively. The normal pan creas enhances significantly more with Gd-DTPA than with Mn-DPDP administered under the conditions of this study. Overall image quality is also greater on the Gd-DTPA-enhanced images. (orig.)

The Normal Fetal Pancreas.

Science.gov (United States)

Kivilevitch, Zvi; Achiron, Reuven; Perlman, Sharon; Gilboa, Yinon

2017-10-01

The aim of the study was to assess the sonographic feasibility of measuring the fetal pancreas and its normal development throughout pregnancy. We conducted a cross-sectional prospective study between 19 and 36 weeks' gestation. The study included singleton pregnancies with normal pregnancy follow-up. The pancreas circumference was measured. The first 90 cases were tested to assess feasibility. Two hundred ninety-seven fetuses of nondiabetic mothers were recruited during a 3-year period. The overall satisfactory visualization rate was 61.6%. The intraobserver and interobserver variability had high interclass correlation coefficients of of 0.964 and 0.967, respectively. A cubic polynomial regression described best the correlation of pancreas circumference with gestational age (r = 0.744; P pancreas circumference percentiles for each week of gestation were calculated. During the study period, we detected 2 cases with overgrowth syndrome and 1 case with an annular pancreas. In this study, we assessed the feasibility of sonography for measuring the fetal pancreas and established a normal reference range for the fetal pancreas circumference throughout pregnancy. This database can be helpful when investigating fetomaternal disorders that can involve its normal development. © 2017 by the American Institute of Ultrasound in Medicine.

Malignant fibrous histiocytoma of pancreas: presentation of a case

International Nuclear Information System (INIS)

Garcia Sanchez, M.A.; Serrano Gotarredona, M.P.; Fernandez-Cruz, J.; Marrero Calvo, S.

1995-01-01

We present a case of malignant fibrous histiocytoma (MFH) located in the body and tail of the pancreas of a 60-year-old woman. The mass was large, lobulated and well delimited by a pseudocapsule. Pancreatectomy involving the body and tail and splenectomy were performed and the diagnosis was reached on the basis of pathological and immunohistochemical studies. The course was aggressive with local recurrence and liver metastases presenting two months after the operation. The computerized tomography (CT) findings are provided. (Author)

Human immunodeficiency virus infection and the liver.

Science.gov (United States)

Crane, Megan; Iser, David; Lewin, Sharon R

2012-03-27

Liver disease in human immunodeficiency virus (HIV)-infected individuals encompasses the spectrum from abnormal liver function tests, liver decompensation, with and without evidence of cirrhosis on biopsy, to non-alcoholic liver disease and its more severe form, non-alcoholic steatohepatitis and hepatocellular cancer. HIV can infect multiple cells in the liver, leading to enhanced intrahepatic apoptosis, activation and fibrosis. HIV can also alter gastro-intestinal tract permeability, leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function. This review focuses on recent changes in the epidemiology, pathogenesis and clinical presentation of liver disease in HIV-infected patients, in the absence of co-infection with hepatitis B virus or hepatitis C virus, with a specific focus on issues relevant to low and middle income countries.

[Gender-specific influencing factors on incidence, risk factors and outcome of carcinoma of the liver, gallbladder, extrahepatic bile duct and pancreas].

Science.gov (United States)

Grundmann, R T; Meyer, F

2014-04-01

This overview comments on gender-specific differences in incidence, risk factors and prognosis in patients with carcinoma of the liver, gallbladder, extrahepatic bile duct and pancreas. For the literature review, the MEDLINE database (PubMed) was searched under the key words "liver cancer", "gallbladder cancer", "extrahepatic bile duct carcinoma", "pancreatic cancer" AND "gender". There were significant gender differences in the epidemiology of the analysed carcinomas. The incidence of hepatocellular carcinoma (HCC) is much higher in men than in women, one of 86 men, but only 1 out of 200 women develop a malignant primary liver tumour in Germany in the course of their life. The lifetime risk for carcinomas of the gallbladder and extrahepatic bile ducts in Germany amounts to about 0.6 % for women and 0.5 % for men, specifically gallbladder carcinomas are observed more frequently in women than in men. For pancreatic cancer, no clear gender preference exists in Germany, although the mortality risk for men is higher than that for women (age-adjusted standardised death rate in men 12.8/100, 000 persons, in women 9.5). Remarkable is furthermore the shift of the tumour incidence in the last decades. Liver cancer has increased among men in Germany by about 50 % in the last 30 years, the incidence of gallbladder carcinoma has inversely dropped. The prognosis of these cancers across all tumour stages is uniformly bad in an unselected patient population. This is probably the main reason why only little - if any - gender differences in survival are described. In addition to avoiding the known risk factors such as hepatitis B and C virus infection, alcohol abuse, and smoking, the avoidance of overweight and obesity plays an increasingly important role in the prevention of these cancers. Georg Thieme Verlag KG Stuttgart · New York.

Arterioscanning of pancreas

International Nuclear Information System (INIS)

Petrovskij, B.V.; Rabkin, I.Kh.; Matevosov, A.L.

1980-01-01

Investigated is the state of precapillary and capillary net of pancreas vessels by way of intra-arterial MAA 1 +H3+H1I injection. Posiible variants of pancreas form, shape and position, and the main sources of blood supply are presented. The knowledge of the above factors is necessary to avoid mistakes in the desiphering of arterioscannograms. Techniques for angiography and arterioscanning in cases of pancreas cancer, benign tumours, pancreas cyst and chronic pancreatitis are described. Arterioscanning is shown to be a valuable addition to angiography, which permits to judge on the angiographically invisible part of the organ arteriolocapillary channel, clarifying the nature of the process and damage length. The summary estimate of results of angiographic and arterioscannographic investigations considerably increases the diagnostic effectiveness

Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

Science.gov (United States)

2014-05-28

Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

Blood flow and tissue oxygen pressures of liver and pancreas in rats: effects of volatile anesthetics and of hemorrhage.

Science.gov (United States)

Vollmar, B; Conzen, P F; Kerner, T; Habazettl, H; Vierl, M; Waldner, H; Peter, K

1992-09-01

The object of this investigation was to compare the effects of volatile anesthetics and of hemorrhage at comparable arterial blood pressures on splanchnic blood flow (radioactive microspheres) and tissue oxygenation of the liver and pancreas (surface PO2 [PSO2] electrodes). In contrast to earlier studies, we did not use identical minimum alveolar anesthetic concentration multiples as a reference to compare volatile anesthetics; rather, we used the splanchnic perfusion pressure. Under general anesthesia (intravenous chloralose) and controlled ventilation, 12 Sprague-Dawley rats underwent laparotomy to allow access to abdominal organs. Mean arterial pressure was decreased from 84 +/- 3 mm Hg (mean +/- SEM) at control to 50 mm Hg by 1.0 +/- 0.1 vol% halothane, 2.2 +/- 0.2 vol% enflurane, and 2.3 +/- 0.1 vol% isoflurane in a randomized sequence. For hemorrhagic hypotension, blood was withdrawn gradually until a mean arterial pressure of 50 mm Hg was attained. Volatile anesthetics and hemorrhage reduced cardiac output, and hepatic arterial, portal venous, and total hepatic blood flows by comparable degrees. Mean hepatic PSO2 decreased significantly from 30.7 +/- 2.6 mm Hg at control to 17.4 +/- 2 and 17.5 +/- 2 mm Hg during enflurane and isoflurane (each P less than 0.05) anesthesia, respectively. The decrease to 11.5 +/- 2.5 mm Hg was more pronounced during halothane anesthesia. Hemorrhagic hypotension was associated with the lowest hepatic PSO2 (3.4 +/- 1.3 mm Hg) and the highest number of hypoxic (0-5 mm Hg 86%) and anoxic PSO2 values (0 mm Hg 46%). Pancreatic blood flow and oxygenation remained unchanged from control during halothane and enflurane administration, whereas isoflurane increased both variables. Hemorrhagic hypotension slightly reduced pancreatic flow (-8%) but significantly decreased PSO2 from 58 +/- 5 mm Hg at control to 36 +/- 3 mm Hg, with 7% of all measured values in the hypoxic range. Thus, volatile anesthetics preserved pancreatic but not hepatic

Proteomic analysis of pancreas derived from adult cloned pig

International Nuclear Information System (INIS)

Chae, Jung-Il; Cho, Young Keun; Cho, Seong-Keun; Kim, Jin-Hoi; Han, Yong-Mahn; Koo, Deog-Bon; Lee, Kyung-Kwang

2008-01-01

The potential medical applications of animal cloning include xenotransplantation, but the complex molecular cascades that control porcine organ development are not fully understood. Still, it has become apparent that organs derived from cloned pigs may be suitable for transplantation into humans. In this study, we examined the pancreas of an adult cloned pig developed through somatic cell nuclear transfer (SCNT) using two-dimensional electrophoresis (2-DE) and Western blotting. Proteomic analysis revealed 69 differentially regulated proteins, including such apoptosis-related species as annexins, lamins, and heat shock proteins, which were unanimously upregulated in the SCNT sample. Among the downregulated proteins in SCNT pancreas were peroxiredoxins and catalase. Western blot results indicate that several antioxidant enzymes and the anti-apoptotic protein were downregulated in SCNT pancreas, whereas several caspases were upregulated. Together, these data suggest that the accumulation of reactive oxygen species (ROS) in the pancreas of an adult cloned pig leads to apoptosis

Expression of receptors for gut peptides in human pancreatic adenocarcinoma and tumour-free pancreas

NARCIS (Netherlands)

Tang, C.; Biemond, I.; Offerhaus, G. J.; Verspaget, W.; Lamers, C. B.

1997-01-01

Gut hormones that modulate the growth of normal pancreas may also modulate the growth of cancers originating from pancreas. This study visualized and compared the receptors for cholecystokinin (CCK), bombesin (BBS), secretin and vasoactive intestinal peptide (VIP) in tumour-free tissue sections of

Inflammation increases cells expressing ZSCAN4 and progenitor cell markers in the adult pancreas

Science.gov (United States)

Azuma, Sakiko; Yokoyama, Yukihiro; Yamamoto, Akiko; Kyokane, Kazuhiro; Niida, Shumpei; Ishiguro, Hiroshi; Ko, Minoru S. H.

2013-01-01

We have recently identified the zinc finger and SCAN domain containing 4 (Zscan4), which is transiently expressed and regulates telomere elongation and genome stability in mouse embryonic stem (ES) cells. The aim of this study was to examine the expression of ZSCAN4 in the adult pancreas and elucidate the role of ZSCAN4 in tissue inflammation and subsequent regeneration. The expression of ZSCAN4 and other progenitor or differentiated cell markers in the human pancreas was immunohistochemically examined. Pancreas sections of alcoholic or autoimmune pancreatitis patients before and under maintenance corticosteroid treatment were used in this study. In the adult human pancreas a small number of ZSCAN4-positive (ZSCAN4+) cells are present among cells located in the islets of Langerhans, acini, ducts, and oval-shaped cells. These cells not only express differentiated cell markers for each compartment of the pancreas but also express other tissue stem/progenitor cell markers. Furthermore, the number of ZSCAN4+ cells dramatically increased in patients with chronic pancreatitis, especially in the pancreatic tissues of autoimmune pancreatitis actively regenerating under corticosteroid treatment. Interestingly, a number of ZSCAN4+ cells in the pancreas of autoimmune pancreatitis returned to the basal level after 1 yr of maintenance corticosteroid treatment. In conclusion, coexpression of progenitor cell markers and differentiated cell markers with ZSCAN4 in each compartment of the pancreas may indicate the presence of facultative progenitors for both exocrine and endocrine cells in the adult pancreas. PMID:23599043

Pancreas transplant - slideshow

Science.gov (United States)

... this page: //medlineplus.gov/ency/presentations/100129.htm Pancreas transplant - series—Normal anatomy To use the sharing ... to slide 6 out of 6 Overview The pancreas resides in the back of the abdomen. It ...

National Pancreas Foundation

Science.gov (United States)

... Stay Informed - Join The Fight Animated Pancreas Patient Animations, Expert and Patient interviews on Pancreas Diseases State ... pancreatic experts at the American Pancreatic Association … Continue Reading More NPF News Social Media Post Read More ...

Pancreas and cyst segmentation

Science.gov (United States)

Dmitriev, Konstantin; Gutenko, Ievgeniia; Nadeem, Saad; Kaufman, Arie

2016-03-01

Accurate segmentation of abdominal organs from medical images is an essential part of surgical planning and computer-aided disease diagnosis. Many existing algorithms are specialized for the segmentation of healthy organs. Cystic pancreas segmentation is especially challenging due to its low contrast boundaries, variability in shape, location and the stage of the pancreatic cancer. We present a semi-automatic segmentation algorithm for pancreata with cysts. In contrast to existing automatic segmentation approaches for healthy pancreas segmentation which are amenable to atlas/statistical shape approaches, a pancreas with cysts can have even higher variability with respect to the shape of the pancreas due to the size and shape of the cyst(s). Hence, fine results are better attained with semi-automatic steerable approaches. We use a novel combination of random walker and region growing approaches to delineate the boundaries of the pancreas and cysts with respective best Dice coefficients of 85.1% and 86.7%, and respective best volumetric overlap errors of 26.0% and 23.5%. Results show that the proposed algorithm for pancreas and pancreatic cyst segmentation is accurate and stable.

Dataset of protein species from human liver

Directory of Open Access Journals (Sweden)

Stanislav Naryzhny

2017-06-01

Full Text Available This article contains data related to the research article entitled “Zipf׳s law in proteomics” (Naryzhny et al., 2017 [1]. The protein composition in the human liver or hepatocarcinoma (HepG2 cells extracts was estimated using a filter-aided sample preparation (FASP protocol. The protein species/proteoform composition in the human liver was determined by two-dimensional electrophoresis (2-DE followed by Electrospray Ionization Liquid Chromatography-Tandem Mass Spectrometry (ESI LC-MS/MS. In the case of two-dimensional electrophoresis (2-DE, the gel was stained with Coomassie Brilliant Blue R350, and image analysis was performed with ImageMaster 2D Platinum software (GE Healthcare. The 96 sections in the 2D gel were selected and cut for subsequent ESI LC-MS/MS and protein identification. If the same protein was detected in different sections, it was considered to exist as different protein species/proteoforms. A list of human liver proteoforms detected in this way is presented.

Annular pancreas (image)

Science.gov (United States)

Annular pancreas is an abnormal ring or collar of pancreatic tissue that encircles the duodenum (the part of the ... intestine that connects to stomach). This portion of pancreas can constrict the duodenum and block or impair ...

Pig Pancreas Anatomy: Implications for Pancreas Procurement, Preservation, and Islet Isolation

Science.gov (United States)

Ferrer, Joana; Scott, William E; Weegman, Bradley P; Suszynski, Thomas M; Sutherland, David E R; Hering, Bernhard J; Papas, Klearchos K

2009-01-01

Background Islet transplantation is emerging as a treatment option for selected patients with type 1 diabetes. The limited human islet supply from cadavers and poor islet yield and quality remain substantial impediments to progress in the field. Use of porcine islets holds great promise for large-scale application of islet transplantation. Consistent isolation of porcine islets is dependent on advances in pancreas procurement and preservation, and islet isolation requiring detailed knowledge of the porcine pancreatic anatomy. The primary aim of this study was to describe the vascular and ductal anatomy of the porcine pancreas in order to guide and improve organ preservation and enzyme perfusion. Methods Pancreata were removed by en bloc viscerectomy from 65 female Landrace pigs. Results 15% of organs exhibited inconsistent vascular branching from the celiac trunk. All organs had uniform patterns of branching at the superior mesenteric artery. The superior and inferior mesenteric veins (IMV) merged to become the portal vein in all but one case in which the IMV drained into the splenic vein. 97% of pancreata had three lobes: duodenal (DL), connecting (CL), and splenic (SL); 39% demonstrated ductal communication between the CL and the other two lobes; 50% had ductal communication only between the CL and DL; and 11% presented other types of ductal delineation. Conclusions Accounting for the variations in vascular and ductal anatomy, as detailed in this study, will facilitate development of protocols for preservation, optimal enzyme administration, and pancreas distention and digestion, and ultimately lead to substantial improvements in isolation outcomes. PMID:19077881

Long-term culture of human liver tissue with advanced hepatic functions.

Science.gov (United States)

Ng, Soon Seng; Xiong, Anming; Nguyen, Khanh; Masek, Marilyn; No, Da Yoon; Elazar, Menashe; Shteyer, Eyal; Winters, Mark A; Voedisch, Amy; Shaw, Kate; Rashid, Sheikh Tamir; Frank, Curtis W; Cho, Nam Joon; Glenn, Jeffrey S

2017-06-02

A major challenge for studying authentic liver cell function and cell replacement therapies is that primary human hepatocytes rapidly lose their advanced function in conventional, 2-dimensional culture platforms. Here, we describe the fabrication of 3-dimensional hexagonally arrayed lobular human liver tissues inspired by the liver's natural architecture. The engineered liver tissues exhibit key features of advanced differentiation, such as human-specific cytochrome P450-mediated drug metabolism and the ability to support efficient infection with patient-derived inoculums of hepatitis C virus. The tissues permit the assessment of antiviral agents and maintain their advanced functions for over 5 months in culture. This extended functionality enabled the prediction of a fatal human-specific hepatotoxicity caused by fialuridine (FIAU), which had escaped detection by preclinical models and short-term clinical studies. The results obtained with the engineered human liver tissue in this study provide proof-of-concept determination of human-specific drug metabolism, demonstrate the ability to support infection with human hepatitis virus derived from an infected patient and subsequent antiviral drug testing against said infection, and facilitate detection of human-specific drug hepatotoxicity associated with late-onset liver failure. Looking forward, the scalability and biocompatibility of the scaffold are also ideal for future cell replacement therapeutic strategies.

Growth-hormone and somatostatin effects on [75Se]selenomethionine uptake by the pancreas

International Nuclear Information System (INIS)

Atkins, H.L.; Som, P.

1979-01-01

The imaging of the pancreas with [ 75 Se]selenomethionine has a low rate of reliability. This study was carried out in order to elucidate some factors that may be important in affecting the degree of uptake of the tracer by the pancreas. Studies were carried out in animals to observe the effects of growth-hormone (GH), somatostatin (SRIF), L-DOPA, and apomorphine administration on the distribution of [ 75 Se]selenomethionine. Intravenously administered GH significantly depressed pancreatic uptake of Se-75 in mice and dogs and depressed the pancreas-to-liver concentration ratio (P/L). The effect of i.p. GH in mice was to decrease the P/L ratio, but the decrease in pancreatic uptake was not statistically significant. There was also a greater effect of GH in dogs than in mice, with pancreatic uptake decreasing from 5.60 +- 2.17% to 1.24 +- 0.96% and the P/L from 4.78 +- 1.85 to 0.97 +- 0.73. L-DOPA and apomorphine produced effects similar to GH in mice. SRIF in small doses had little effect, but in larger doses it enhanced pancreatic uptake, although not affecting P/L. The results indicate that hypothalamic factors may be important in affecting the function of the exocrine pancreas. Both L-DOPA and apomorphine are known to stimulate GH production through hypothalamic-pituitary pathways. In addition to suppressing GH release, SRIF may have direct effects on the exocrine pancreas

A study of human liver ferritin and chicken liver and spleen using Moessbauer spectroscopy with high velocity resolution

Energy Technology Data Exchange (ETDEWEB)

Oshtrakh, M. I., E-mail: oshtrakh@mail.utnet.ru [Ural State Technical University-UPI, Faculty of Physical Techniques and Devices for Quality Control (Russian Federation); Milder, O. B.; Semionkin, V. A. [Ural State Technical University-UPI, Faculty of Experimental Physics (Russian Federation)

2008-01-15

Lyophilized samples of human liver ferritin and chicken liver and spleen were measured at room temperature using Moessbauer spectroscopy with high velocity resolution. An increase in the velocity resolution of Moessbauer spectroscopy permitted us to increase accuracy and decrease experimental error in determining the hyperfine parameters of human liver ferritin and chicken liver and spleen. Moessbauer spectroscopy with high velocity resolution may be very useful for revealing small differences in hyperfine parameters during biomedical research.

CT scans in studies of the dynamics of liposynthesis and lipolysis of the human liver

International Nuclear Information System (INIS)

Huebener, K.H.; Schmitt, W.G.H.

1981-01-01

Following an analysis of the most important metabolic disturbances and other diseases associated ith fatty degeneration of the liver, it is shown, basing on a previous study, by means of examples, that subtle diagnosis of changes of the fatty content of the liver can be achieved via CT density measurement. Lipolysis in alcoholic fatty liver is quantified during abstention from alcohol, and a lipolysis factor of 1% fatty decomposition per day is determined from the measurements. Observations in pancreatitis with liver lipid storage during the course of the disease, point to an enzymatic weakness in lipid metabolism. Case histories show fatty degeneration associated with an enhanced cortisone serum level (in adrenal adenoma and cortisone therapy) and in poorly stabilized diabetes mellitus. It is concluded from the studies that determination of the relative fatty content by CT densitometry should be conducted as a routine procedure and that pathological lipid content should stimulate subtle diagnosis of the pancreas and the adrenals. In addition, examinations repeated during the course of the disease with assessment of changes in fatty content, will be useful for assessing the value of the therapy employed. (orig.) [de

CT scans in studies of the dynamics of liposynthesis and lipolysis of the human liver

Energy Technology Data Exchange (ETDEWEB)

Huebener, K H; Schmitt, W G.H.

1981-06-01

Following an analysis of the most important metabolic disturbances and other diseases associated with fatty degeneration of the liver, it is shown, basing on a previous study, by means of examples, that subtle diagnosis of changes of the fatty content of the liver can be achieved via CT density measurement. Lipolysis in alcoholic fatty liver is quantified during abstention from alcohol, and a lipolysis factor of 1% fatty decomposition per day is determined from the measurements. Observations in pancreatitis with liver lipid storage during the course of the disease, point to an enzymatic weakness in lipid metabolism. Case histories show fatty degeneration associated with an enhanced cortisone serum level (in adrenal adenoma and cortisone therapy) and in poorly stabilized diabetes mellitus. It is concluded from the studies that determination of the relative fatty content by CT densitometry should be conducted as a routine procedure and that pathological lipid content should stimulate subtle diagnosis of the pancreas and the adrenals. In addition, examinations repeated during the course of the disease with assessment of changes in fatty content, will be useful for assessing the value of the therapy employed.

Activin B mediated induction of Pdx1 in human embryonic stem cell derived embryoid bodies

DEFF Research Database (Denmark)

Frandsen, Ulrik; Pørneki, Ann Dorte Storm; Floridon, Charlotte

2007-01-01

embryonic and fetal pancreas anlage in humans. Pdx1(+) cells are found in cell clusters also expressing Serpina1 and FABP1, suggesting activation of intestinal/liver developmental programs. Moreover, Activin B up-regulates Sonic Hedgehog (Shh) and its target Gli1, which during normal development...

Hepatic cholesterol ester hydrolase in human liver disease.

Science.gov (United States)

Simon, J B; Poon, R W

1978-09-01

Human liver contains an acid cholesterol ester hydrolase (CEH) of presumed lysosomal origin, but its significance is unknown. We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy. Histologically normal livers hydrolyzed 5.80 +/- 0.78 SEM mumoles of cholesterol ester per hr per g of liver protein (n, 10). Values were similar in alcoholic liver disease (n, 17), obstructive jaundice (n, 9), and miscellaneous hepatic disorders (n, 21). In contrast, mean hepatic CEH activity was more than 3-fold elevated in 12 patients with acute hepatitis, 21.05 +/- 2.45 SEM mumoles per hr per g of protein (P less than 0.01). In 2 patients studied serially, CEH returned to normal as hepatitis resolved. CEH activity in all patients paralleled SGOT levels (r, 0.84; P less than 0.01). There was no correlation with serum levels of free or esterified cholesterol nor with serum activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. These studies confirm the presence of CEH activity in human liver and show markedly increased activity in acute hepatitis. The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study.

Three-dimensional reconstructions of intrahepatic bile duct tubulogenesis in human liver

DEFF Research Database (Denmark)

Vestentoft, Peter S; Jelnes, Peter; Hopkinson, Branden M

2011-01-01

BACKGROUND: During liver development, intrahepatic bile ducts are thought to arise by a unique asymmetric mode of cholangiocyte tubulogenesis characterized by a series of remodeling stages. Moreover, in liver diseases, cells lining the Canals of Hering can proliferate and generate new hepatic...... in normal liver and in the extensive ductular reactions originating from intrahepatic bile ducts and branching into the parenchyma of the acetaminophen intoxicated liver. In the developing human liver, three-dimensional reconstructions using multiple marker proteins confirmed that the human intrahepatic...

IL-4 mRNA Is Downregulated in the Liver of Pancreatic Cancer Patients Suffering from Cachexia.

Science.gov (United States)

Prokopchuk, Olga; Steinacker, Jürgen M; Nitsche, Ulrich; Otto, Stephanie; Bachmann, Jeannine; Schubert, Elaine C; Friess, Helmut; Martignoni, Marc E

2017-01-01

Interleukin-4 (IL-4) together with interleukin-13 (IL-13) play an important role in inflammation and wound repair, and are known to be upregulated in human skeletal muscle after strenuous physical exercise. Additionally, these cytokines may act as autocrine growth factors in pancreatic cancer cells. We hypothesize that IL-4, IL-13, and their corresponding receptors are involved in mechanism of cancer cachexia. Tissue samples from human skeletal muscle, white fat, liver, healthy pancreas, and pancreatic ductal adenocarcinoma were analyzed by quantitative real-time polymerase chain reaction for mRNA expression levels of IL-4, IL-13, IL-4 receptor α, and IL-13 receptor α1. We demonstrate for the first time that liver IL-4 mRNA is downregulated in vivo in patients with pancreatic cancer and cachexia. Additionally, IL-4 mRNA in the liver inversely correlated with musculus psoas thickness. We speculate that suppression of IL-4 is involved in cancer cachexia, although the exact mechanisms have to be further elucidated.

Portal Annular Pancreas

Science.gov (United States)

Harnoss, Jonathan M.; Harnoss, Julian C.; Diener, Markus K.; Contin, Pietro; Ulrich, Alexis B.; Büchler, Markus W.; Schmitz-Winnenthal, Friedrich H.

2014-01-01

Abstract Portal annular pancreas (PAP) is an asymptomatic congenital pancreas anomaly, in which portal and/or mesenteric veins are encased by pancreas tissue. The aim of the study was to determine the role of PAP in pancreatic surgery as well as its management and potential complication, specifically, postoperative pancreatic fistula (POPF). On the basis of a case report, the MEDLINE and ISI Web of Science databases were systematically reviewed up to September 2012. All articles describing a case of PAP were considered. In summary, 21 studies with 59 cases were included. The overall prevalence of PAP was 2.4% and the patients' mean (SD) age was 55.9 (16.2) years. The POPF rate in patients with PAP (12 pancreaticoduodenectomies and 3 distal pancreatectomies) was 46.7% (in accordance with the definition of the International Study Group of Pancreatic Surgery). Portal annular pancreas is a quite unattended pancreatic variant with high prevalence and therefore still remains a clinical challenge to avoid postoperative complications. To decrease the risk for POPF, attentive preoperative diagnostics should also focus on PAP. In pancreaticoduodenectomy, a shift of the resection plane to the pancreas tail should be considered; in extensive pancreatectomy, coverage of the pancreatic remnant by the falciform ligament could be a treatment option. PMID:25207658

Effect of the Human Amniotic Membrane on Liver Regeneration in Rats

Directory of Open Access Journals (Sweden)

Mesut Sipahi

2015-01-01

Full Text Available Introduction. Operations are performed for broader liver surgery indications for a better understanding of hepatic anatomy/physiology and developments in operation technology. Surgery can cure some patients with liver metastasis of some tumors. Nevertheless, postoperative liver failure is the most feared complication causing mortality in patients who have undergone excision of a large liver mass. The human amniotic membrane has regenerative effects. Thus, we investigated the effects of the human amniotic membrane on regeneration of the resected liver. Methods. Twenty female Wistar albino rats were divided into control and experimental groups and underwent a 70% hepatectomy. The human amniotic membrane was placed over the residual liver in the experimental group. Relative liver weight, histopathological features, and biochemical parameters were assessed on postoperative day 3. Results. Total protein and albumin levels were significantly lower in the experimental group than in the control group. No difference in relative liver weight was observed between the groups. Hepatocyte mitotic count was significantly higher in the experimental group than in the control group. Hepatic steatosis was detected in the experimental group. Conclusion. Applying the amniotic membrane to residual liver adversely affected liver regeneration. However, mesenchymal stem cell research has the potential to accelerate liver regeneration investigations.

Molecular Structure of Human-Liver Glycogen.

Directory of Open Access Journals (Sweden)

Bin Deng

Full Text Available Glycogen is a highly branched glucose polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets.

Generation of Functional Beta-Like Cells from Human Exocrine Pancreas.

Directory of Open Access Journals (Sweden)

Maria J Lima

Full Text Available Transcription factor mediated lineage reprogramming of human pancreatic exocrine tissue could conceivably provide an unlimited supply of islets for transplantation in the treatment of diabetes. Exocrine tissue can be efficiently reprogrammed to islet-like cells using a cocktail of transcription factors: Pdx1, Ngn3, MafA and Pax4 in combination with growth factors. We show here that overexpression of exogenous Pax4 in combination with suppression of the endogenous transcription factor ARX considerably enhances the production of functional insulin-secreting β-like cells with concomitant suppression of α-cells. The efficiency was further increased by culture on laminin-coated plates in media containing low glucose concentrations. Immunocytochemistry revealed that reprogrammed cultures were composed of ~45% islet-like clusters comprising >80% monohormonal insulin+ cells. The resultant β-like cells expressed insulin protein levels at ~15-30% of that in adult human islets, efficiently processed proinsulin and packaged insulin into secretory granules, exhibited glucose responsive insulin secretion, and had an immediate and prolonged effect in normalising blood glucose levels upon transplantation into diabetic mice. We estimate that approximately 3 billion of these cells would have an immediate therapeutic effect following engraftment in type 1 diabetes patients and that one pancreas would provide sufficient tissue for numerous transplants.

Four cases of solid pseudopapillary tumors of pancreas: Imaging findings and pathological correlations

International Nuclear Information System (INIS)

Vargas-Serrano, Blanca; Dominguez-Ferreras, Esther; Chinchon-Espino, David

2006-01-01

Objective: Solid pseudopapillary tumor of the pancreas (SPTP tumor) is a rare pancreatic neoplasm with low malignant potential, which usually affects female patients in the second or third decades of life. It is a non-functional, slow-growing neoplasm that very often reaches considerable size before the first symptoms appear. Symptomatology is frequently related to tumor size. Surgical excision is usually curative in most cases. Infrequently the tumor can appear in male patients or in aged women, which can make the diagnosis more difficult. Some patients develop liver metastases in the follow-up that can be resected. Our purpose is to review the radiological and pathological findings of SPTP with emphasis on these infrequent cases. Subjects and methods: The medical records and radiological findings of patients who underwent surgery for SPTP between 2000 and 2005 were retrospectively reviewed. Study eligibility required that patients had undergone surgical resection and that a SPTP had been pathologically proved. Results: Four cases of solid pseudopapillary tumor of the pancreas were diagnosed and treated in our institution in the study period. Two of the patients, developed on follow-up liver metastases, and peritoneal, hepatic, and nodal metastases, respectively. Conclusion: Solid pseudopapillary tumors are well-encapsulated neoplasms that usually have a good prognosis after surgical excision. A malignant behavior is uncommon and in this case lymph node involvement, hepatic metastases and occasionally peritoneal invasion may also occur. Resection of liver metastases can prolong the long-term survival of the patients

Characterization of Insulin-Immunoreactive Cells and Endocrine Cells Within the Duct System of the Adult Human Pancreas.

Science.gov (United States)

Li, Rong; Zhang, Xiaoxi; Yu, Lan; Zou, Xia; Zhao, Hailu

2016-01-01

The adult pancreatic duct system accommodates endocrine cells that have the potential to produce insulin. Here we report the characterization and distribution of insulin-immunoreactive cells and endocrine cells within the ductal units of adult human pancreas. Sequential pancreas sections from 12 nondiabetic adults were stained with biomarkers of ductal epithelial cells (cytokeratin 19), acinar cells (amylase), endocrine cells (chromogranin A; neuron-specific enolase), islet hormones (insulin, glucagon, somatostatin, pancreatic polypeptide), cell proliferation (Ki-67), and neogenesis (CD29). The number of islet hormone-immunoreactive cells increased from large ducts to the terminal branches. The insulin-producing cells outnumbered endocrine cells reactive for glucagon, somatostatin, or pancreatic polypeptide. The proportions of insulin-immunoreactive count compared with local islets (100% as a baseline) were 1.5% for the main ducts, 7.2% for interlobular ducts, 24.8% for intralobular ducts, 67.9% for intercalated ducts, and 348.9% for centroacinar cells. Both Ki-67- and CD29-labeled cells were predominantly localized in the terminal branches around the islets. The terminal branches also showed cells coexpressing islet hormones and cytokeratin 19. The adult human pancreatic ducts showed islet hormone-producing cells. The insulin-reactive cells predominantly localized in terminal branches where they may retain potential capability for β-cell neogenesis.

Current status of prediction of drug disposition and toxicity in humans using chimeric mice with humanized liver.

Science.gov (United States)

Kitamura, Shigeyuki; Sugihara, Kazumi

2014-01-01

1. Human-chimeric mice with humanized liver have been constructed by transplantation of human hepatocytes into several types of mice having genetic modifications that injure endogenous liver cells. Here, we focus on liver urokinase-type plasminogen activator-transgenic severe combined immunodeficiency (uPA/SCID) mice, which are the most widely used human-chimeric mice. Studies so far indicate that drug metabolism, drug transport, pharmacological effects and toxicological action in these mice are broadly similar to those in humans. 2. Expression of various drug-metabolizing enzymes is known to be different between humans and rodents. However, the expression pattern of cytochrome P450, aldehyde oxidase and phase II enzymes in the liver of human-chimeric mice resembles that in humans, not that in the host mice. 3. Metabolism of various drugs, including S-warfarin, zaleplon, ibuprofen, naproxen, coumarin, troglitazone and midazolam, in human-chimeric mice is mediated by human drug-metabolizing enzymes, not by host mouse enzymes, and thus resembles that in humans. 4. Pharmacological and toxicological effects of various drugs in human-chimeric mice are also similar to those in humans. 5. The current consensus is that chimeric mice with humanized liver are useful to predict drug metabolism catalyzed by cytochrome P450, aldehyde oxidase and phase II enzymes in humans in vivo and in vitro. Some remaining issues are discussed in this review.

Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice.

Science.gov (United States)

Salgueiro, Andréia Caroline Fernandes; Folmer, Vanderlei; da Silva, Marianne Pires; Mendez, Andreas Sebastian Loureiro; Zemolin, Ana Paula Pegoraro; Posser, Thaís; Franco, Jeferson Luis; Puntel, Robson Luiz; Puntel, Gustavo Orione

2016-01-01

This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF) tea on oxidative stress and liver damage in streptozotocin (STZ)-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1) BF chemical composition; (2) glucose levels; (3) liver/body weight ratio and liver transaminases; (4) reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation in liver; (5) superoxide dismutase (SOD) and catalase (CAT) activities in liver; (6) δ-aminolevulinate dehydratase (δ-ALA-D) and nonprotein thiols (NPSH) in liver; (7) Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential.

Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice

Directory of Open Access Journals (Sweden)

Andréia Caroline Fernandes Salgueiro

2016-01-01

Full Text Available This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF tea on oxidative stress and liver damage in streptozotocin (STZ-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1 BF chemical composition; (2 glucose levels; (3 liver/body weight ratio and liver transaminases; (4 reactive oxygen species (ROS, lipid peroxidation, and protein carbonylation in liver; (5 superoxide dismutase (SOD and catalase (CAT activities in liver; (6 δ-aminolevulinate dehydratase (δ-ALA-D and nonprotein thiols (NPSH in liver; (7 Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential.

In vivo imaging of vesicular monoamine transporter 2 in pancreas using an {sup 18}F epoxide derivative of tetrabenazine

Energy Technology Data Exchange (ETDEWEB)

Kung, Hank F. [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 (United States)], E-mail: kunghf@sunmac.spect.upenn.edu; Lieberman, Brian P. [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Zhuang Zhiping [Avid Radiopharmaceuticals, Inc., Philadelphia, PA 19104 (United States); Oya, Shunichi; Kung Meiping [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Choi, Seok Rye [Avid Radiopharmaceuticals, Inc., Philadelphia, PA 19104 (United States); Poessl, Karl; Blankemeyer, Eric; Hou, Catherine [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Skovronsky, Daniel [Avid Radiopharmaceuticals, Inc., Philadelphia, PA 19104 (United States); Kilbourn, Michael [Department of Radiology, University of Michigan, Ann Arbor, MI 48109 (United States)

2008-11-15

Objectives: Development of imaging agents for pancreatic beta cell mass may provide tools for studying insulin-secreting beta cells and their relationship with diabetes mellitus. In this paper, a new imaging agent, [{sup 18}F](+)-2-oxiranyl-3-isobutyl-9-(3-fluoropropoxy)-10-methoxy-2,3,4,6,7, 11b-hexahydro-1H-pyrido[2,1-a]isoquinoline [{sup 18}F](+)4, which displays properties targeting vesicular monoamine transporter 2 (VMAT2) binding sites of beta cells in the pancreas, was evaluated as a positron emission tomography (PET) agent for estimating beta cell mass in vivo. The hydrolyzable epoxide group of (+)4 may provide a mechanism for shifting biodistribution from liver to kidney, thus reducing the background signal. Methods: Both {sup 18}F- and {sup 19}F-labeled (+) and (-) isomers of 4 were synthesized and evaluated. Organ distribution was carried out in normal rats. Uptake of [{sup 18}F](+)4 in pancreas of normal rats was measured and correlated with blocking studies using competing drugs, (+)dihydrotetrabenazine [(+)-DTBZ] or 9-fluoropropyl-(+)dihydro tetrabenazine [FP-(+)-DTBZ, (+)2]. Results: In vitro binding study of VMAT2 using rat brain striatum showed a K{sub i} value of 0.08 and 0.15 nM for the (+)4 and ({+-})4, respectively. The in vivo biodistribution of [{sup 18}F](+)4 in rats showed the highest uptake in the pancreas (2.68 %ID/g at 60 min postinjection). In vivo competition experiments with cold FP-(+)-DTBZ, (+)2, (3.5 mg/kg, 5 min iv pretreatment) led to a significant reduction of pancreas uptake (85% blockade at 60 min). The inactive isomer [{sup 18}F](-)4 showed significantly lower pancreas uptake (0.22 %ID/g at 30 min postinjection). Animal PET imaging studies of [{sup 18}F](+)4 in normal rats demonstrated an avid pancreatic uptake in rats. Conclusion: The preliminary results suggest that the epoxide, [{sup 18}F](+)4, is highly selective in binding to VMAT2 and it has an excellent uptake in the pancreas of rats. The liver uptake was significantly

MRI of islet cell tumors of the pancreas

International Nuclear Information System (INIS)

Ohtomo, Kuni; Itai, Yuji; Yoshikawa, Koki; Kokubo, Taka; Yashiro, Naofumi; Iio, Masahiro; Atomi, Yu

1986-01-01

Magnetic resonance imaging (MRI) was performed in five patients with islet cell tumors of the pancreas, using 0.35 T and 1.5 T superconductive magnets. MRI identified tumors in 3 patients. The tumors seen in the 3 patients appeared as areas of higher signal intensity than the liver on spin-echo (SE) images with repetition time of 1,600 msec/echo time of 35 or 70 msec, and as areas of similar or lower intensity on SE 400/35 or 70 images. The tumor imaged by SE techniques with 1,600/35 msec, 400/35 msec, and 1,600/35 or 70 msec in one patient was manifested by prolongation of T1 and T2, as compared with the liver. Tumors in the remaining two patients, which were not detected on MRI, were 15 mm or smaller. MRI remains to be improved in the visualization of small lesions. (Namekawa, K.)

A registry analysis of damage to the deceased donor pancreas during procurement.

Science.gov (United States)

Ausania, F; Drage, M; Manas, D; Callaghan, C J

2015-11-01

Surgical injury to the pancreas is thought to occur commonly during procurement. The UK Transplant Registry was analyzed to determine the frequency of pancreatic injuries, identify factors associated with damage, and assess the impact of injuries on graft survival. Twelve hundred ninety-six pancreata were procured from donation after brain death donors, with 314 (19.5%) from donation after circulatory death donors. More than 50% of recovered pancreata had at least one injury, most commonly a short portal vein (21.5%). Liver donation, procurement team origin, hepatic artery (HA) arising from the superior mesenteric artery (SMA), and increasing donor BMI were associated with increased rates of pancreas damage on univariate analyses; on multivariate analysis only the presence of an HA from the SMA remained significant (p = 0.02). Six hundred forty solid organ pancreas transplants were performed; 238 had some form of damage. Overall, there was no difference in graft survival between damaged and undamaged organs (p = 0.28); however, graft loss was significantly more frequent in pancreata with arterial damage (p = 0.04) and in those with parenchymal damage (p = 0.05). Damage to the pancreas during organ recovery is more common than other organs, and meticulous surgical technique and awareness of damage risk factors are essential to reduce rates of procurement-related injuries. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Minimally Invasive Management of Ectopic Pancreas.

Science.gov (United States)

Vitiello, Gerardo A; Cavnar, Michael J; Hajdu, Cristina; Khaykis, Inessa; Newman, Elliot; Melis, Marcovalerio; Pachter, H Leon; Cohen, Steven M

2017-03-01

The management of ectopic pancreas is not well defined. This study aims to determine the prevalence of symptomatic ectopic pancreas and identify those who may benefit from treatment, with a particular focus on robotically assisted surgical management. Our institutional pathology database was queried to identify a cohort of ectopic pancreas specimens. Additional clinical data regarding clinical symptomatology, diagnostic studies, and treatment were obtained through chart review. Nineteen cases of ectopic pancreas were found incidentally during surgery for another condition or found incidentally in a pathologic specimen (65.5%). Eleven patients (37.9%) reported prior symptoms, notably abdominal pain and/or gastrointestinal bleeding. The most common locations for ectopic pancreas were the duodenum and small bowel (31% and 27.6%, respectively). Three out of 29 cases (10.3%) had no symptoms, but had evidence of preneoplastic changes on pathology, while one harbored pancreatic cancer. Over the years, treatment of ectopic pancreas has shifted from open to laparoscopic and more recently to robotic surgery. Our experience is in line with existing evidence supporting surgical treatment of symptomatic or complicated ectopic pancreas. In the current era, minimally invasive and robotic surgery can be used safely and successfully for treatment of ectopic pancreas.

PVA matches human liver in needle-tissue interaction.

Science.gov (United States)

de Jong, Tonke L; Pluymen, Loes H; van Gerwen, Dennis J; Kleinrensink, Gert-Jan; Dankelman, Jenny; van den Dobbelsteen, John J

2017-05-01

Medical phantoms can be used to study needle-tissue interaction and to train medical residents. The purpose of this research is to study the suitability of polyvinyl alcohol (PVA) as a liver tissue mimicking material in terms of needle-tissue interaction. Insertions into ex-vivo human livers were used for reference. Six PVA samples were created by varying the mass percentage of PVA to water (4m% and 7m%) and the number of freeze-thaw cycles (1, 2 and 3 cycles, 16hours of freezing at -19°C, 8hours of thawing). The inner needle of an 18 Gauge trocar needle with triangular tip was inserted 13 times into each of the samples, using an insertion velocity of 5 mm/s. In addition, 39 insertions were performed in two ex-vivo human livers. Axial forces on the needle were captured during insertion and retraction and characterized by friction along the needle shaft, peak forces, and number of peak forces per unit length. The concentration of PVA and the number of freeze-thaw cycles both influenced the mechanical interaction between needle and specimen. Insertions into 4m% PVA phantoms with 2 freeze-thaw cycles were comparable to human liver in terms of estimated friction along the needle shaft and the number of peak forces. Therefore, these phantoms are considered to be suitable liver mimicking materials for image-guided needle interventions. The mechanical properties of PVA hydrogels can be influenced in a controlled manner by varying the concentration of PVA and the number of freeze-thaw cycles, to mimic liver tissue characteristics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ultrasonography of the canine pancreas

Directory of Open Access Journals (Sweden)

Michelle L Avante

2018-01-01

Full Text Available This study describes the ultrasonographic techniques currently used in the evaluation of the canine pancreas. Ultrasonography was the first method to enable direct visualization of the pancreas in humans and it has been subsequently applied to animals. Currently, it is the method of choice for pancreatic evaluation and is essential as a diagnostic tool in the detection of abnormalities, especially tumors. Innovative equipment technology has led to the emergence of techniques complementary to B-mode ultrasound; such as Doppler, elastography, and contrast-enhanced ultrasonography, which have enabled more accurate diagnosis. Doppler provides information on vascular architecture and the hemodynamic aspect of blood vessels in multiple organs. ARFI elastography provides detailed images of the alterations detected by conventional examination (qualitative method and assists in differentiating between benign and malignant processes (quantitative method. Microbubble contrast agents determine parameters related to homogeneous and heterogeneous filling of organs with microbubbles, mainly nodular areas, thus defining high and low intensity patterns.

Metabolic profiles of pomalidomide in human plasma simulated with pharmacokinetic data in control and humanized-liver mice.

Science.gov (United States)

Shimizu, Makiko; Suemizu, Hiroshi; Mitsui, Marina; Shibata, Norio; Guengerich, F Peter; Yamazaki, Hiroshi

2017-10-01

1. Pomalidomide has been shown to be potentially teratogenic in thalidomide-sensitive animal species such as rabbits. Screening for thalidomide analogs devoid of teratogenicity/toxicity - attributable to metabolites formed by cytochrome P450 enzymes - but having immunomodulatory properties is a strategic pathway towards development of new anticancer drugs. 2. In this study, plasma concentrations of pomalidomide, its primary 5-hydroxylated metabolite, and its glucuronide conjugate(s) were investigated in control and humanized-liver mice. Following oral administration of pomalidomide (100 mg/kg), plasma concentrations of 7-hydroxypomalidomide and 5-hydroxypomalidomide glucuronide were slightly higher in humanized-liver mice than in control mice. 3. Simulations of human plasma concentrations of pomalidomide were achieved with simplified physiologically-based pharmacokinetic models in both groups of mice in accordance with reported pomalidomide concentrations after low dose administration in humans. 4. The results indicate that pharmacokinetic profiles of pomalidomide were roughly similar between control mice and humanized-liver mice and that control and humanized-liver mice mediated pomalidomide 5-hydroxylation in vivo. Introducing one aromatic amino group into thalidomide resulted in less species differences in in vivo pharmacokinetics in control and humanized-liver mice.

CT diagnosis of annular pancreas

International Nuclear Information System (INIS)

Ueno, Eiko; Isobe, Yoshinori; Niimi, Akiko; Shimizu, Yasushi; Yamada, Akiyoshi; Hanyu, Fujio

1987-01-01

CT scan was performed in two cases of annular pancreas which could be found in one case preoperatively and in the other case retrospectively. CT scan demonstrated secondary changes of annular pancreas such as medial displacement and dilatation of the duodenal bulb in the former case and stenosis of the duodenal loop and thickened soft tissue density around the narrow segment of the duodenal loop in the latter case, although it failed to demonstrate the peninsular protrusion of the parenchyma of the pancreas head. These findings suggest high possibility of diagnosing annular pancreas by CT scan. (author)

Stabilization of beta-catenin induces pancreas tumor formation.

Science.gov (United States)

Heiser, Patrick W; Cano, David A; Landsman, Limor; Kim, Grace E; Kench, James G; Klimstra, David S; Taketo, Maketo M; Biankin, Andrew V; Hebrok, Matthias

2008-10-01

beta-Catenin signaling within the canonical Wnt pathway is essential for pancreas development. However, the pathway is normally down-regulated in the adult organ. Increased cytoplasmic and nuclear localization of beta-catenin can be detected in nearly all human solid pseudopapillary neoplasms (SPN), a rare tumor with low malignant potential. Conversely, pancreatic ductal adenocarcinoma (PDA) accounts for the majority of pancreatic tumors and is among the leading causes of cancer death. Whereas activating mutations within beta-catenin and other members of the canonical Wnt pathway are rare, recent reports have implicated Wnt signaling in the development and progression of human PDA. Here, we sought to address the role of beta-catenin signaling in pancreas tumorigenesis. Using Cre/lox technology, we conditionally activated beta-catenin in a subset of murine pancreatic cells in vivo. Activation of beta-catenin results in the formation of large pancreatic tumors at a high frequency in adult mice. These tumors resemble human SPN based on morphologic and immunohistochemical comparisons. Interestingly, stabilization of beta-catenin blocks the formation of pancreatic intraepithelial neoplasia (PanIN) in the presence of an activating mutation in Kras that is known to predispose individuals to PDA. Instead, mice in which beta-catenin and Kras are concurrently activated develop distinct ductal neoplasms that do not resemble PanIN lesions. These results demonstrate that activation of beta-catenin is sufficient to induce pancreas tumorigenesis. Moreover, they indicate that the sequence in which oncogenic mutations are acquired has profound consequences on the phenotype of the resulting tumor.

Cell sources for in vitro human liver cell culture models

Science.gov (United States)

Freyer, Nora; Damm, Georg; Seehofer, Daniel; Knöspel, Fanny

2016-01-01

In vitro liver cell culture models are gaining increasing importance in pharmacological and toxicological research. The source of cells used is critical for the relevance and the predictive value of such models. Primary human hepatocytes (PHH) are currently considered to be the gold standard for hepatic in vitro culture models, since they directly reflect the specific metabolism and functionality of the human liver; however, the scarcity and difficult logistics of PHH have driven researchers to explore alternative cell sources, including liver cell lines and pluripotent stem cells. Liver cell lines generated from hepatomas or by genetic manipulation are widely used due to their good availability, but they are generally altered in certain metabolic functions. For the past few years, adult and pluripotent stem cells have been attracting increasing attention, due their ability to proliferate and to differentiate into hepatocyte-like cells in vitro. However, controlling the differentiation of these cells is still a challenge. This review gives an overview of the major human cell sources under investigation for in vitro liver cell culture models, including primary human liver cells, liver cell lines, and stem cells. The promises and challenges of different cell types are discussed with a focus on the complex 2D and 3D culture approaches under investigation for improving liver cell functionality in vitro. Finally, the specific application options of individual cell sources in pharmacological research or disease modeling are described. PMID:27385595

Australia and New Zealand Islets and Pancreas Transplant Registry Annual Report 2017—Pancreas Waiting List, Recipients, and Donors

Science.gov (United States)

Webster, Angela C; Hedley, James; Patekar, Abhijit; Robertson, Paul; Kelly, Patrick J

2017-01-01

Abstract This is a registry report from the Australia and New Zealand Islet and Pancreas Transplant Registry. We report data for all solid organ pancreas transplant activity from inception in 1984 to end of 2016. Data analysis was performed using Stata Software version 14 (StataCorp, College Station, Tex). From 1984 to 2016 a total of 756 solid organ pancreas transplants have been performed in Australia and New Zealand, in 738 individuals. In 2016, 55 people received a pancreas transplant. These transplants were performed in Auckland (4), Monash (22), and Westmead (29). In 2016, 50 transplants were simultaneous pancreas kidney, 4 were pancreas after kidney, and 1 was a pancreas transplant alone. PMID:29026874

Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.

Science.gov (United States)

Bacalini, Maria Giulia; Franceschi, Claudio; Gentilini, Davide; Ravaioli, Francesco; Zhou, Xiaoyuan; Remondini, Daniel; Pirazzini, Chiara; Giuliani, Cristina; Marasco, Elena; Gensous, Noémie; Di Blasio, Anna Maria; Ellis, Ewa; Gramignoli, Roberto; Castellani, Gastone; Capri, Miriam; Strom, Stephen; Nardini, Christine; Cescon, Matteo; Grazi, Gian Luca; Garagnani, Paolo

2018-03-15

The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8823 age-associated differentially methylated CpG probes. Notably, these age-associated changes tended to level off after the age of 60, as confirmed by Horvath's clock. Using stringent selection criteria we further identified a DNA methylation signature of aging liver including 75 genomic regions. We demonstrated that this signature is specific for liver compared to other tissues and that it is able to detect biological age-acceleration effects associated with obesity. Finally we combined DNA methylation measurements with available expression data. Although the intersection between the two omic characterizations was low, both approaches suggested a previously unappreciated role of epithelial-mesenchymal transition and Wnt signaling pathways in the aging of human liver.

GPR39 splice variants versus antisense gene LYPD1: expression and regulation in gastrointestinal tract, endocrine pancreas, liver, and white adipose tissue

DEFF Research Database (Denmark)

Egerod, Kristoffer L; Holst, Birgitte; Petersen, Pia S

2007-01-01

nervous system as characterized with both quantitative RT-PCR and in situ hybridization analysis. A functional analysis of the GPR39 promoter region identified sites for the hepatocyte nuclear factors 1alpha and 4alpha (HNF-1alpha and -4alpha) and specificity protein 1 (SP1) transcription factors as being......G protein-coupled receptor 39 (GPR39) is a constitutively active, orphan member of the ghrelin receptor family that is activated by zinc ions. GPR39 is here described to be expressed in a full-length, biologically active seven-transmembrane form, GPR39-1a, as well as in a truncated splice variant...... five-transmembrane form, GPR39-1b. The 3' exon of the GPR39 gene overlaps with an antisense gene called LYPD1 (Ly-6/PLAUR domain containing 1). Quantitative RT-PCR analysis demonstrated that GPR39-1a is expressed selectively throughout the gastrointestinal tract, including the liver and pancreas...

Antihyperglycaemic and organic protective effects on pancreas, liver and kidney by polysaccharides from Hericium erinaceus SG-02 in streptozotocin-induced diabetic mice.

Science.gov (United States)

Zhang, Chen; Li, Juan; Hu, Chunlong; Wang, Jing; Zhang, Jianjun; Ren, Zhenzhen; Song, Xinling; Jia, Le

2017-09-07

The present work was designed to investigate the antihyperglycaemic and protective effects of two Hericium erinaceus intracellular polysaccharide (HIPS) purified fractions (HIPS1 and HIPS2) from mycelia of H. erinaceus SG-02 on pancreas, liver and kidney in streptozotocin (STZ)-induced diabetic mice. The supplementation of HIPS1 and HIPS2 significantly decreased the blood glucose (GLU) levels; suppressed the abnormal elevations of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN) and creatinine (CRE) levels in serum; improved the antioxidant enzymatic (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)) activities; and attenuated the pathological damage to these organs. The HIPS1 showed superior effects in antihyperglycaemia and organic protection than HIPS2 possible owing to the abundant functional groups (-NH 2 , -COOH and S=O) in HIPS1, indicating that H. erinaceus SG-02 could be used as a functional food and natural drug for the prevention of diabetes and its complications.

Computer tomography (CT) finding of normal pancreas

International Nuclear Information System (INIS)

Cho, Chi Ja; Kim, Byung Tae; Lee, Jeung Suk

1983-01-01

Conventional radiology of the pancreas are too often unsatisfactory. It is well known that the whole body CT is very useful in identifying retroperitoneal pathology. The authors intended to present normal pancreatic morphology and data for preparation of basis for interpretation of abnormalities. We results were as follows; 1. There were 36 male and 24 female patients, and their ages ranged from 7 to 78 years. 2. 1) The organs adjacent pancreas were stomach, inferior vena cava, duodenum, caudate lobe of the liver left kidney, left adrenal gland, superior mesenteric vessels, spleen. 2) In 19 patients, pancreatic tail at the level of left kidney in the transverse plane, it was either ventral in 13 (68%), ventromedial in 2 (19%), ventrolateral in 4 (21%) to left kidney, in the other 41 patients, it was cranial to the upper pole of left kidney, ventral in 25 (61%), ventromedial in 1 (2%), ventrolateral in 15 (37%). 3) Pancreatic tail was cranial to the pancreatic body, 3 cm cranial in 2 (4%), 2-3 cm in 5 (8%), 1-2 cm in 6 (10%), less than 1 cm in 11 (18%). In the other, caudal in 3 (5%). 4) Pancreatic tail was cranial to the level of the splenic hilum in 36 (60%), 0-2 cm caudal in 24 (40%). 3. Pancreatic shape was uniform tapering form in 37 (62%), lobulated form in 23 (38%). 4. Pancreatic orientation was horizontal in 13 (22%), vertical 56 (76%), S-shaped in 1 (2%). 5. Pancreatic margin was smooth in 22 (37%), lobulated in 38 (63%). 6. In most patients, pancreas was uniform in density. 7. Pancreatic size was 0.5 ± 0.1 in measurement ratio of the head in 48 (80%), 0.4 ± 0.1 of the body in 49 (88%), 0.5 ± 0.1 of the tail in 47 (78%)

Serglycin proteoglycan is not implicated in localizing exocrine pancreas enzymes to zymogen granules

DEFF Research Database (Denmark)

Niemann, Carsten U; Cowland, Jack B; Ralfkiaer, Elisabeth

2009-01-01

Storage and release of proteins from granules forms the basis of cellular functions as diverse as cell mediated cytotoxicity, neuronal communication, activation of muscle fibres, and release of hormones or digestive enzymes from endocrine and exocrine glands, such as the pancreas. Serglycin...... is the major intracellular proteoglycan of haematopoietic cells. Serglycin is important for localization of proteins in granules of different haematopoietic cell types. Previous reports have indicated a role for serglycin in granule formation and localization of zymogens in granules of the exocrine pancreas...... in rat. We here present data showing that serglycin is not present at the protein level in human or murine pancreas. Furthermore, the amount and localization of three exocrine pancreas zymogens (amylase, trypsinogen, and carboxypeptidase A) is not affected by the absence of serglycin in a serglycin knock...

[A case report-advanced pancreas cancer with liver and lung metastases well controlled over one year by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion in an outpatient setting].

Science.gov (United States)

Hasuike, Yasunori; Tanigawa, Takahiko; Yamada, Masaharu; Minami, Yukiko; Ezumi, Koji; Kashiwazaki, Masaki; Fujimoto, Takayoshi

2008-11-01

We report a case of advanced pancreatic cancer with liver and lung metastases that was well controlled over one year by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion in an outpatient setting. The patient was a 74-year-old woman. Chief complaints were back pain and anorexia. She was diagnosed with pancreas cancer with liver and lung metastases at the time of first visit. We started systemic chemotherapy with gemcitabine 1 g/body and 5-FU 1 g/body alternately every other week on an outpatient basis. At 1.5 months (M) after initiation of chemotherapy, we started radiation therapy to the main tumor at a total dose of 40 Gy. After radiation, chemotherapy was resumed. As a result, the size of the main tumor decreased but metastatic liver tumors got larger. Then we changed to combination therapy with systemic chemotherapy (gemcitabine and 5-FU) and hepatic arterial infusion (5-FU weekly). Liver metastases almost disappeared after 7.5 M. Despite all these treatments, however, the number of metastatic lung tumors increased. The patient was hospitalized for 15 M and died after 17 M. We focused on and succeeded in the prolongation of lifetime and maintenance of QOL by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion therapy.

The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytes

International Nuclear Information System (INIS)

Parkinson, Andrew; Mudra, Daniel R.; Johnson, Cory; Dwyer, Anne; Carroll, Kathleen M.

2004-01-01

We have measured cytochrome P450 (CYP) activity in nearly 150 samples of human liver microsomes and 64 samples of cryopreserved human hepatocytes, and we have performed induction studies in over 90 preparations of cultured human hepatocytes. We have analyzed these data to examine whether the expression of CYP enzyme activity in liver microsomes and isolated hepatocytes or the inducibility of CYP enzymes in cultured hepatocytes is influenced by the gender, age, or ethnicity of the donor (the latter being limited to Caucasians, African Americans, and Hispanics due to a paucity of livers from Asian donors). In human liver microsomes, there were no statistically significant differences (P > 0.05) in CYP activity as a function of age, gender, or ethnicity with one exception. 7-Ethoxyresorufin O-dealkylase (CYP1A2) activity was greater in males than females, which is consistent with clinical observation. Liver microsomal testosterone 6β-hydroxylase (CYP3A4) activity was slightly greater in females than males, but the difference was not significant. However, in cryopreserved human hepatocytes, the gender difference in CYP3A4 activity (females = twice males) did reach statistical significance, which supports the clinical observation that females metabolize certain CYP3A4 substrates faster than do males. Compared with those from Caucasians and African Americans, liver microsomes from Hispanics had about twice the average activity of CYP2A6, CYP2B6, and CYP2C8 and half the activity of CYP1A2, although this apparent ethnic difference may be a consequence of the relatively low number of Hispanic donors. Primary cultures of hepatocytes were treated with β-naphthoflavone, an inducer of CYP1A2, phenobarbital or rifampin, both of which induce CYP2B6, CYP2C9, CYP2C19, and CYP3A4, albeit it to different extents. Induction of these CYP enzymes in freshly cultured hepatocytes did not appear to be influenced by the gender or age of the donor. Furthermore, CYP3A4 induction in

Assessment of emerging biomarkers of liver injury in human subjects.

Science.gov (United States)

Schomaker, Shelli; Warner, Roscoe; Bock, Jeff; Johnson, Kent; Potter, David; Van Winkle, Joyce; Aubrecht, Jiri

2013-04-01

Hepatotoxicity remains a major challenge in drug development. Although alanine aminotransferase (ALT) remains the gold standard biomarker of liver injury, alternative biomarker strategies to better predict the potential for severe drug-induced liver injury (DILI) are essential. In this study, we evaluated the utility of glutamate dehydrogenase (GLDH), purine nucleoside phosphorylase (PNP), malate dehydrogenase (MDH), and paraxonase 1 (PON1) as indicators of liver injury in cohorts of human subjects, including healthy subjects across age and gender, subjects with a variety of liver impairments, and several cases of acetaminophen poisoning. In the healthy subjects, levels of GLDH and MDH were not affected by age or gender. Reference ranges for GLDH and MDH in healthy subjects were 1-10 and 79-176U/L, respectively. In contrast, the levels of PON1 and PNP were not consistent across cohorts of healthy subjects. Furthermore, GLDH and MDH had a strong correlation with elevated ALT levels and possessed a high predictive power for liver injury, as determined by ROC analysis. In contrast, PON1 and PNP did not detect liver injury in our study. Finally, evaluation of patients with acetaminophen-induced liver injury provided evidence that both GLDH and MDH might have utility as biomarkers of DILI in humans. This study is the first to evaluate GLDH, MDH, PON1, and PNP in a large number of human subjects and, and it provides an impetus for prospective clinical studies to fully evaluate the diagnostic value of GLDH and MDH for detection of liver injury.

Stem cells and the pancreas: from discovery to clinical approach

Directory of Open Access Journals (Sweden)

Angelica Dessì

2016-02-01

Full Text Available The existence of stem cells within the adult pancreas is supported by the ability of this organ to regenerate its endocrine component in various conditions such as pregnancy and following partial pancreatectomy. Several studies have shown that progenitor or adult stem cells may reside within the pancreas and particularly in the pancreatic ducts, including acinar cells and islets of Langerhans. The discovery of human pluripotent stem cells in the pancreas, and the possibility of development of strategies for generating these, represented a turning point for the therapeutic interventions of type 1 diabetes.Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

Cranberry juice suppressed the diclofenac metabolism by human liver microsomes, but not in healthy human subjects

Science.gov (United States)

Ushijima, Kentarou; Tsuruoka, Shu-ichi; Tsuda, Hidetoshi; Hasegawa, Gohki; Obi, Yuri; Kaneda, Tae; Takahashi, Masaki; Maekawa, Tomohiro; Sasaki, Tomohiro; Koshimizu, Taka-aki; Fujimura, Akio

2009-01-01

AIM To investigate a potential interaction between cranberry juice and diclofenac, a substrate of CYP2C9. METHODS The inhibitory effect of cranberry juice on diclofenac metabolism was determined using human liver microsome assay. Subsequently, we performed a clinical trial in healthy human subjects to determine whether the repeated consumption of cranberry juice changed the diclofenac pharmacokinetics. RESULTS Cranberry juice significantly suppressed diclofenac metabolism by human liver microsomes. On the other hand, repeated consumption of cranberry juice did not influence the diclofenac pharmacokinetics in human subjects. CONCLUSIONS Cranberry juice inhibited diclofenac metabolism by human liver microsomes, but not in human subjects. Based on the present and previous findings, we think that although cranberry juice inhibits CYP2C9 activity in vitro, it does not change the pharmacokinetics of medications metabolized by CYP2C9 in clinical situations. PMID:19694738

Feasibility of automated 3-dimensional magnetic resonance imaging pancreas segmentation

Directory of Open Access Journals (Sweden)

Shuiping Gou, PhD

2016-07-01

Conclusions: Our study demonstrated potential feasibility of automated segmentation of the pancreas on MRI scans with minimal human supervision at the beginning of imaging acquisition. The achieved accuracy is promising for organ localization.

Serous cystadenocarcinoma of pancreas

International Nuclear Information System (INIS)

Rathore, M. U.; Arif, A.; Umair, B.

2013-01-01

Serous cystic neoplasms of pancreas are relatively rare tumours. Malignancy in these tumours is even more rare which is confirmed by metastasis to other organs or by perineural, vascular or surrounding soft tissue invasion. A 60 years old lady presented with vague upper abdominal pain. Computed tomography scan showed multiloculated cystic mass in the body of pancreas measuring 9 x 6 x 5 cm and not involving spleen. Pancreatectomy specimen showed a multicystic tumour having sponge-like appearance which showed vascular and soft tissue invasion of surrounding stroma on microscopic examination and was diagnosed as serous cystadenocarcinoma of pancreas. (author)

Human precision-cut liver slices as a model to test antifibrotic drugs in the early onset of liver fibrosis

NARCIS (Netherlands)

Westra, Inge M.; Mutsaers, Henricus A. M.; Luangmonkong, Theerut; Hadi, Mackenzie; Oosterhuis, Dorenda; de Jong, Koert P.; Groothuis, Geny M. M.; Olinga, Peter

Liver fibrosis is the progressive accumulation of connective tissue ultimately resulting in loss of organ function. Currently, no effective antifibrotics are available due to a lack of reliable human models. Here we investigated the fibrotic process in human precision-cut liver slices (PCLS) and

Single-Cell Analysis of Human Pancreas Reveals Transcriptional Signatures of Aging and Somatic Mutation Patterns.

Science.gov (United States)

Enge, Martin; Arda, H Efsun; Mignardi, Marco; Beausang, John; Bottino, Rita; Kim, Seung K; Quake, Stephen R

2017-10-05

As organisms age, cells accumulate genetic and epigenetic errors that eventually lead to impaired organ function or catastrophic transformation such as cancer. Because aging reflects a stochastic process of increasing disorder, cells in an organ will be individually affected in different ways, thus rendering bulk analyses of postmitotic adult cells difficult to interpret. Here, we directly measure the effects of aging in human tissue by performing single-cell transcriptome analysis of 2,544 human pancreas cells from eight donors spanning six decades of life. We find that islet endocrine cells from older donors display increased levels of transcriptional noise and potential fate drift. By determining the mutational history of individual cells, we uncover a novel mutational signature in healthy aging endocrine cells. Our results demonstrate the feasibility of using single-cell RNA sequencing (RNA-seq) data from primary cells to derive insights into genetic and transcriptional processes that operate on aging human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

Interaction of rocuronium with human liver cytochromes P450

OpenAIRE

Anzenbacherova, Eva; Spicakova, Alena; Jourova, Lenka; Ulrichova, Jitka; Adamus, Milan; Bachleda, Petr; Anzenbacher, Pavel

2015-01-01

Rocuronium is a neuromuscular blocking agent acting as a competitive antagonist of acetylcholine. Results of an inhibition of eight individual liver microsomal cytochromes P450 (CYP) are presented. As the patients are routinely premedicated with diazepam, possible interaction of diazepam with rocuronium has been also studied. Results indicated that rocuronium interacts with human liver microsomal CYPs by binding to the substrate site. Next, concentration dependent inhibition of liver micro...

Selection of suitable prodrug candidates for in vivo studies via in vitro studies; the correlation of prodrug stability in between cell culture homogenates and human tissue homogenates.

Science.gov (United States)

Tsume, Yasuhiro; Amidon, Gordon L

2012-01-01

To determine the correlations/discrepancies of drug stabilities between in the homogenates of human culture cells and of human tissues. Amino acid/dipeptide monoester prodrugs of floxuridine were chosen as the model drugs. The stabilities (half-lives) of floxuridine prodrugs in human tissues (pancreas, liver, and small intestine) homogenates were obtained and compared with ones in cell culture homogenates (AcPC-1, Capan-2, and Caco-2 cells) as well as human liver microsomes. The correlations of prodrug stability in human small bowel tissue homogenate vs. Caco-2 cell homogenate, human liver tissue homogenate vs. human liver microsomes, and human pancreatic tissue homogenate vs. pancreatic cell, AsPC-1 and Capan-2, homogenates were examined. The stabilities of floxuridine prodrugs in human small bowel homogenate exhibited the great correlation to ones in Caco-2 cell homogenate (slope = 1.0-1.3, r2 = 0.79-0.98). The stability of those prodrugs in human pancreas tissue homogenate also exhibited the good correlations to ones in AsPC-1 and Capan-2 cells homogenates (slope = 0.5-0.8, r2 = 0.58-0.79). However, the correlations of prodrug stabilities between in human liver tissue homogenates and in human liver microsomes were weaker than others (slope = 1.3-1.9, r2 = 0.07-0.24). The correlations of drug stabilities in cultured cell homogenates and in human tissue homogenates were compared. Those results exhibited wide range of correlations between in cell homogenate and in human tissue homogenate (r2 = 0.07 - 0.98). Those in vitro studies in cell homogenates would be good tools to predict drug stabilities in vivo and to select drug candidates for further developments. In the series of experiments, 5'-O-D-valyl-floxuridine and 5'-O-L-phenylalanyl-L-tyrosyl-floxuridine would be selected as candidates of oral drug targeting delivery for cancer chemotherapy due to their relatively good stabilities compared to other tested prodrugs.

[DEVELOPMENT OF FUNCTIONAL AND MORPHOLOGICAL CHANGES OF A PANCREAS DEPENDING ON THE DURATION OF OBSTRUCTIVE CHOLESTASIS].

Science.gov (United States)

Belyaev, A N; Kostin, S V; Belyaev, S A

2015-01-01

To study the severity and timing of the development of functional (reversible) and morphological (irreversible) disturbances in the pancreas, depending on the duration of obstructive cholestasis. Obstructive jaundice in the experiment 18 dogs modeled by applying the loop stranglehold on the common bile duct, followed by observation for 30 days. We measured total bilirubin and fractions aspartate aminotransferase activity (AST) and alanine aminotransferase (ALT), the contents alpha-amylase, pancreatic lipase, glucose, histological examination of the pancreas (magnification of 100 times and 400). On day 3 the common bile duct obstruction bilirubin increased from 7.1 to 286.8 μmol/l, ALT--from 0.17 to 4.18 μmol*h/l, alpha-amylase from 89 to 186 U/L and lipase--to 68 to 179 U/L. Then there was a slight decrease in the parameters studied with repeated their increase to 15 hours. Morphological changes in the first three days were characterized by reversible (swelling), impaired organ that 14-16 days passed in organic (irreversible) changes. Dynamics of fluctuations in the level of liver enzymes in the pancreas and obstructive cholestasis correlates with morphological abnormalities in the pancreas and fit into the concept of general biological organism's reaction to injury.

Augmenter of liver regeneration (ALR) protects human hepatocytes against apoptosis

Energy Technology Data Exchange (ETDEWEB)

Ilowski, Maren [Liver Regeneration Group, Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Kleespies, Axel [Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Toni, Enrico N. de [Department of Medicine II, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Donabauer, Barbara [Liver Regeneration Group, Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Jauch, Karl-Walter [Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Hengstler, Jan G. [Leibniz Research Centre for Working Environment and Human Factors, Technical University, Dortmund (Germany); Thasler, Wolfgang E., E-mail: wolfgang.thasler@med.uni-muenchen.de [Liver Regeneration Group, Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany)

2011-01-07

Research highlights: {yields} ALR decreases cytochrome c release from mitochondria. {yields} ALR protects hepatocytes against apoptosis induction by ethanol, TRAIL, anti-Apo, TGF-{beta} and actinomycin D. {yields} ALR exerts a liver-specific anti-apoptotic effect. {yields} A possible medical usage of ALR regarding protection of liver cells during apoptosis inducing therapies. -- Abstract: Augmenter of liver regeneration (ALR) is known to support liver regeneration and to stimulate proliferation of hepatocytes. However, it is not known if ALR exerts anti-apoptotic effects in human hepatocytes and whether this protective effect is cell type specific. This is relevant, because compounds that protect the liver against apoptosis without undesired effects, such as protection of metastatic tumour cells, would be appreciated in several clinical settings. Primary human hepatocytes (phH) and organotypic cancer cell lines were exposed to different concentrations of apoptosis inducers (ethanol, TRAIL, anti-Apo, TGF-{beta}, actinomycin D) and cultured with or without recombinant human ALR (rhALR). Apoptosis was evaluated by the release of cytochrome c from mitochondria and by FACS with propidium iodide (PI) staining. ALR significantly decreased apoptosis induced by ethanol, TRAIL, anti-Apo, TGF-{beta} and actinomycin D. Further, the anti-apoptotic effect of ALR was observed in primary human hepatocytes and in HepG2 cells but not in bronchial (BC1), colonic (SW480), gastric (GC1) and pancreatic (L3.6PL) cell lines. Therefore, the hepatotrophic growth factor ALR acts in a liver specific manner with regards to both its mitogenic and its anti-apoptotic effect. Unlike the growth factors HGF and EGF, rhALR acts in a liver specific manner. Therefore, ALR is a promising candidate for further evaluation as a possible hepatoprotective factor in clinical settings.

Augmenter of liver regeneration (ALR) protects human hepatocytes against apoptosis

International Nuclear Information System (INIS)

Ilowski, Maren; Kleespies, Axel; Toni, Enrico N. de; Donabauer, Barbara; Jauch, Karl-Walter; Hengstler, Jan G.; Thasler, Wolfgang E.

2011-01-01

Research highlights: → ALR decreases cytochrome c release from mitochondria. → ALR protects hepatocytes against apoptosis induction by ethanol, TRAIL, anti-Apo, TGF-β and actinomycin D. → ALR exerts a liver-specific anti-apoptotic effect. → A possible medical usage of ALR regarding protection of liver cells during apoptosis inducing therapies. -- Abstract: Augmenter of liver regeneration (ALR) is known to support liver regeneration and to stimulate proliferation of hepatocytes. However, it is not known if ALR exerts anti-apoptotic effects in human hepatocytes and whether this protective effect is cell type specific. This is relevant, because compounds that protect the liver against apoptosis without undesired effects, such as protection of metastatic tumour cells, would be appreciated in several clinical settings. Primary human hepatocytes (phH) and organotypic cancer cell lines were exposed to different concentrations of apoptosis inducers (ethanol, TRAIL, anti-Apo, TGF-β, actinomycin D) and cultured with or without recombinant human ALR (rhALR). Apoptosis was evaluated by the release of cytochrome c from mitochondria and by FACS with propidium iodide (PI) staining. ALR significantly decreased apoptosis induced by ethanol, TRAIL, anti-Apo, TGF-β and actinomycin D. Further, the anti-apoptotic effect of ALR was observed in primary human hepatocytes and in HepG2 cells but not in bronchial (BC1), colonic (SW480), gastric (GC1) and pancreatic (L3.6PL) cell lines. Therefore, the hepatotrophic growth factor ALR acts in a liver specific manner with regards to both its mitogenic and its anti-apoptotic effect. Unlike the growth factors HGF and EGF, rhALR acts in a liver specific manner. Therefore, ALR is a promising candidate for further evaluation as a possible hepatoprotective factor in clinical settings.

Analysis of iron storage proteins in chicken liver and spleen tissues in comparison with human liver ferritin by Moessbauer spectroscopy

International Nuclear Information System (INIS)

Oshtrakh, M.I.; Milder, O.B.; Semionkin, V.A.; Malakheeva, L.I.; Prokopenko, P.G.

2006-01-01

Characterization of iron storage proteins in liver and spleen from normal chicken and chicken with lymphoid leukemia in comparison with human liver ferritin were considered by Moessbauer spectroscopy (preliminary results). Small differences in Moessbauer hyperfine parameters for both normal and lymphoid leukemia chicken liver and spleen were observed. The value of quadrupole splitting for human liver ferritin was higher than those for chicken tissues. A decrease of iron content in lymphoid leukemia chicken tissues was also found, however, the reason of this fact (pathology or feeding) was not clear yet. (author)

AGE WISE HISTOMORPHOLOGICAL CHANGES IN HUMAN LIVER

Directory of Open Access Journals (Sweden)

Tribeni

2015-11-01

Full Text Available CONTEXT: Hepato cellular carcinoma (HCC results in between 2.5 lakhs to 1million deaths globally per annum. Liver transplantation nowadays is a well accepted treatment option for end-stage liver disease and acute liver failure. AIMS: Keeping this concept in view, a study was conducted in the Guwahati Zone of Northeast India, to compare the histomorphological features of the human liver in different age groups. SETTING AND DESIGN: Apparently healthy livers were obtained from 21 subjects on whom medicolegal post-mortems had been performed. Their ages varied from newborn to 90 years. Subjects were divided into 3 groups. 7 specimens were taken from each group. (1 Pediatric (2 Adult (3 Old age. METHODS AND MATERIALS: In all the above age groups, immediately after removal of the livers, they were washed in normal saline, dried with blotting paper and weighed in an electronic weighing machine. Sections of liver were fixed, processed, cut and stained with Harris Haematoxylin and Eosin stain. RESULTS: The liver loses weight from 50 years onwards. There appears to be racial and environmental differences in the change in liver weight in old age. Autopsy studies show a diminution of nearly 46% in liver weight between the 3rd and 10th decades of life. The liver decreases in size with age. The hepatocytes are radially disposed in the liver lobule. They are piled up, forming a layer one cell thick (except in young children in a fashion similar to the bricks of a wall. These plates are directed from the periphery of the lobule to its centre and anastomose freely forming a complex labyrinthine and sponge-like structure. CONCLUSIONS: From the findings in the present study it can be concluded that: 1. Nowadays, the measurement of liver volume has gained practical use in relation to liver transplantation. 2. We have compared the histomorphology of adult liver with a child. The findings in both the groups are very similar. This feature is important, since in

Radiocolloid Uptake in the Pancreas Islet Cell Tumor: Case Report

Energy Technology Data Exchange (ETDEWEB)

Yang, W. J.; Chung, S. K.; Yeon, S. K.; Shinn, K. S.; Bahk, Y. W. [Catholic University College of Medicine, Seoul (Korea, Republic of)

1994-03-15

Colloid uptake in various hepatic conditions such as focal nodular hyperplasia, regenerating nodular in the cirrhotic liver, hamartoma, hemangioma and rarely hepatoma has been documented. Extrahepatic tumors may show colloid uptake and they include splenic hemangioma, malignant fibrous histiocytoma, breast carcinoma and Kaposi's sarcoma. The mechanism of colloid uptake in those lesions is associated with phagocytic activity in or around the tumors. We report a pancreas islet cell tumor that showed colloid uptake on {sup 99m}Tc-phytate liver scan without histologic evidence of phagocytosis by tumor cells or infiltration of phagocytes in the tumor. Microscopically the tumor was highly vascular and showed diffuse hemorrhage throughout the tumor. We postulated that extravasation of the colloid into the tumor interstitium caused nonspecific colloid uptake in this tumor. It is expected that hemorrhagic tumor may show nonspecific colloid uptake without phagocytosis in or about the lesion.

Radiocolloid Uptake in the Pancreas Islet Cell Tumor: Case Report

International Nuclear Information System (INIS)

Yang, W. J.; Chung, S. K.; Yeon, S. K.; Shinn, K. S.; Bahk, Y. W.

1994-01-01

Colloid uptake in various hepatic conditions such as focal nodular hyperplasia, regenerating nodular in the cirrhotic liver, hamartoma, hemangioma and rarely hepatoma has been documented. Extrahepatic tumors may show colloid uptake and they include splenic hemangioma, malignant fibrous histiocytoma, breast carcinoma and Kaposi's sarcoma. The mechanism of colloid uptake in those lesions is associated with phagocytic activity in or around the tumors. We report a pancreas islet cell tumor that showed colloid uptake on 99m Tc-phytate liver scan without histologic evidence of phagocytosis by tumor cells or infiltration of phagocytes in the tumor. Microscopically the tumor was highly vascular and showed diffuse hemorrhage throughout the tumor. We postulated that extravasation of the colloid into the tumor interstitium caused nonspecific colloid uptake in this tumor. It is expected that hemorrhagic tumor may show nonspecific colloid uptake without phagocytosis in or about the lesion.

Assessment of pancreas cells

Science.gov (United States)

Vanoss, C. J.

1978-01-01

Pancreatic islets were obtained from guinea pig pancreas by the collagenase method and kept alive in tissue culture prior to further studies. Pancreas cell morphology was studied by standard histochemical techniques using light microscopy. Preparative vertical electrophoresis-levitation of dispersed fetal guinea pig pancreas cells was conducted in phosphate buffer containing a heavy water (D20) gradient which does not cause clumping of cells or alter the osmolarity of the buffers. The faster migrating fractions tended to be enriched in beta-cell content. Alpha and delta cells were found to some degree in most fractions. A histogram showing the cell count distribution is included.

Microencapsulation of Pancreatic Islets for Use in a Bioartificial Pancreas

Science.gov (United States)

Opara, Emmanuel C.; McQuilling, John P.; Farney, Alan C.

2013-01-01

Islet transplantation is the most exciting treatment option for individuals afflicted with Type 1 diabetes. However, the severe shortage of human pancreas and the need to use risky immunosuppressive drugs to prevent transplant rejection remain two major obstacles for the routine use of islet transplantation in diabetic patients. Successful development of a bioartificial pancreas using the approach of microencapsulation with perm-selective coating of islets with biopolymers for graft immunoisolation holds tremendous promise for diabetic patients because it has great potential to overcome these two barriers. In this chapter, we provide a detailed description of the microencapsulation process. PMID:23494435

Radiology of the pancreas

International Nuclear Information System (INIS)

Baert, A.L.; Delorme, G.

1994-01-01

This book, written by internationally recognized experts, fully illustrates the diagnosis of both common and rarer diseases of the pancreas, the latest technical developments in relevant imaging modalities are thoroughly discussed and appraised with respect to the pancreas. The book will appeal to both clinicians and researchers in radiology and oncology. (orig.)

Genetics Home Reference: Pearson marrow-pancreas syndrome

Science.gov (United States)

... Health Conditions Pearson marrow-pancreas syndrome Pearson marrow-pancreas syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Pearson marrow-pancreas syndrome is a severe disorder that usually begins ...

Planimetric correlation between the submandibular glands and the pancreas: a postmortem ductographic study.

Science.gov (United States)

Stimec, Bojan V; Rakocevic, Zoran; Ignjatovic, Dejan; Fasel, Jean H D

2018-01-01

The salivary glands and pancreas have comparable anatomic and antigenic properties and can share common pathogenetic mechanisms involving toxic or autoimmune processes. The aim of this study is to assess the correlation in size between the normal submandibular glands and the pancreas. The study was based on human autopsy specimens of the pancreas, neck and oral base from 22 adults, both sexes (mean age, 57.9 years). The pancreatic and submandibular ducts were injected with a contrast medium, and the area of the salivary and pancreatic glandular ductograms was measured with the aid of software for quantification of visual information. Samples of tissue from the salivary glands and the pancreas were studied by means of light microscopy. A high correlation was found between the planimetric size of the pancreas and the submandibular glands (correlation coefficient 0.497 and 0.699 for the right and the left gland, respectively). This ratio was close to 5:1. There were no significant differences in size for the left vs. right submandibular gland (p = 0.39). The ductograms were significantly larger in size in males than in females (p pancreas, a result that is expected to have possible clinical implications in the long-term follow-up of patients with chronic pancreatitis.

Molecular cloning and nucleotide sequence of cDNA for human liver arginase

International Nuclear Information System (INIS)

Haraguchi, Y.; Takiguchi, M.; Amaya, Y.; Kawamoto, S.; Matsuda, I.; Mori, M.

1987-01-01

Arginase (EC3.5.3.1) catalyzes the last step of the urea cycle in the liver of ureotelic animals. Inherited deficiency of the enzyme results in argininemia, an autosomal recessive disorder characterized by hyperammonemia. To facilitate investigation of the enzyme and gene structures and to elucidate the nature of the mutation in argininemia, the authors isolated cDNA clones for human liver arginase. Oligo(dT)-primed and random primer human liver cDNA libraries in λ gt11 were screened using isolated rat arginase cDNA as a probe. Two of the positive clones, designated λ hARG6 and λ hARG109, contained an overlapping cDNA sequence with an open reading frame encoding a polypeptide of 322 amino acid residues (predicted M/sub r/, 34,732), a 5'-untranslated sequence of 56 base pairs, a 3'-untranslated sequence of 423 base pairs, and a poly(A) segment. Arginase activity was detected in Escherichia coli cells transformed with the plasmid carrying λ hARG6 cDNA insert. RNA gel blot analysis of human liver RNA showed a single mRNA of 1.6 kilobases. The predicted amino acid sequence of human liver arginase is 87% and 41% identical with those of the rat liver and yeast enzymes, respectively. There are several highly conserved segments among the human, rat, and yeast enzymes

Endoscopic ultrasound and pancreas divisum

DEFF Research Database (Denmark)

Rana, Surinder S; Gonen, Can; Vilmann, Peter

2012-01-01

Pancreas divisum is the most common congenital anatomic variation of the pancreatic ductal anatomy and in most of the individuals it is asymptomatic. However, in minority of individuals it is presumed to cause recurrent acute pancreatitis and chronic pancreatitis. Endoscopic retrograde cholangiop......Pancreas divisum is the most common congenital anatomic variation of the pancreatic ductal anatomy and in most of the individuals it is asymptomatic. However, in minority of individuals it is presumed to cause recurrent acute pancreatitis and chronic pancreatitis. Endoscopic retrograde...... of the parenchyma also. Therefore EUS, both radial and linear, has potential for being a minimally invasive diagnostic modality for pancreas divisum. A number of EUS criteria have been suggested for the diagnosis of pancreas divisum. These criteria have varying sensitivity and specificity and hence there is a need...

Laparoscopic robot-assisted pancreas transplantation: first world experience.

Science.gov (United States)

Boggi, Ugo; Signori, Stefano; Vistoli, Fabio; D'Imporzano, Simone; Amorese, Gabriella; Consani, Giovanni; Guarracino, Fabio; Marchetti, Piero; Focosi, Daniele; Mosca, Franco

2012-01-27

Surgical complications are a major disincentive to pancreas transplantation, despite the undisputed benefits of restored insulin independence. The da Vinci surgical system, a computer-assisted electromechanical device, provides the unique opportunity to test whether laparoscopy can reduce the morbidity of pancreas transplantation. Pancreas transplantation was performed by robot-assisted laparoscopy in three patients. The first patient received a pancreas after kidney transplant, the second a simultaneous pancreas kidney transplantation, and the third a pancreas transplant alone. Operations were carried out through an 11-mm optic port, two 8-mm operative ports, and a 7-cm midline incision. The latter was used to introduce the grafts, enable vascular cross-clamping, and create exocrine drainage into the jejunum. The two solitary pancreas transplants required an operating time of 3 and 5 hr, respectively; the simultaneous pancreas kidney transplantation took 8 hr. Mean warm ischemia time of the pancreas graft was 34 min. All pancreatic transplants functioned immediately, and all recipients became insulin independent. The kidney graft, revascularized after 35 min of warm ischemia, also functioned immediately. No patient had complications during or after surgery. At the longer follow-up of 10, 8, and 6 months, respectively, all recipients are alive with normal graft function. We have shown the feasibility of laparoscopic robot-assisted solitary pancreas and simultaneous pancreas and kidney transplantation. If the safety and feasibility of this procedure can be confirmed by larger series, laparoscopic robot-assisted pancreas transplantation could become a new option for diabetic patients needing beta-cell replacement.

Multimodal treatment utilizing intraoperative radiotherapy for advanced cancer of the pancreas

International Nuclear Information System (INIS)

Onodera, Tokio

1982-01-01

A multimodal treatment was consisted of intraoperative radiation, external radiation, by-pass operation, chemotherapy and total parenteral nutrition if necessary to cover decreased oral-intake. Thirty-three cases were subjected to this therapy for 6 years. The stage of the tumors varied from a localized tumor in the pancreas to a huge tumor with multiple metastases, though the latter abandoned recently to be contraindication to this therapy. At laparotomy, a high energy electron beam was irradiated to the tumor with a dosage of 3,000 rad using a 20 MeV Betatron. The tumor was carefully prepared in order to avoid irradiating the duodenum and stomach. Choledochojejunostomy and gastrojejunostomy were performed in almost all of patients with cancer of head of pancreas. In some patients, external radiation was added with a dosage of 3,000 rad by linear X-ray. After radiotherapy, chemotherapy employing 5-FU or FT-207 was continued including. The survival time after this therapy was varied mainly according to the stages of the tumor. In patients with multiple metastasis to the liver or peritoneal dissemination, no remarkable effects were obtained by this therapy. On the otherhand, among 14 patients with localized tumor in the pancreas, 7 survived more than one year and the mean survival time of treated patients was nevershorter than that of patients who received resection of the tumor. Most of the treated patients could spend at home until their condition became critical, because by-pass operation could overcome jaundice or the duodenal stenosis and intraoperative radiation could palliate the pain of cancer of pancreas. Tumor effect of intraoperative radiation was confirmed by both of the second laporatomy for twice intraoperative radiation and laparatomy. (author)

Targeting developmental regulators of zebrafish exocrine pancreas as a therapeutic approach in human pancreatic cancer

Directory of Open Access Journals (Sweden)

Nelson S. Yee

2012-02-01

Histone deacetylases (HDACs and RNA polymerase III (POLR3 play vital roles in fundamental cellular processes, and deregulation of these enzymes has been implicated in malignant transformation. Hdacs and Polr3 are required for exocrine pancreatic epithelial proliferation during morphogenesis in zebrafish. We aim to test the hypothesis that Hdacs and Polr3 cooperatively control exocrine pancreatic growth, and combined inhibition of HDACs and POLR3 produces enhanced growth suppression in pancreatic cancer. In zebrafish larvae, combination of a Hdac inhibitor (Trichostatin A and an inhibitor of Polr3 (ML-60218 synergistically prohibited the expansion of exocrine pancreas. In human pancreatic adenocarcinoma cells, combination of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA and ML-60218 produced augmented suppression of colony formation and proliferation, and induction of cell cycle arrest and apoptotic cell death. The enhanced cytotoxicity was associated with supra-additive upregulation of the pro-apoptotic regulator BAX and the cyclin-dependent kinase inhibitor p21CDKN1A. tRNAs have been shown to have pro-proliferative and anti-apoptotic roles, and SAHA-stimulated expression of tRNAs was reversed by ML-60218. These findings demonstrate that chemically targeting developmental regulators of exocrine pancreas can be translated into an approach with potential impact on therapeutic response in pancreatic cancer, and suggest that counteracting the pro-malignant side effect of HDAC inhibitors can enhance their anti-tumor activity.

Resection for secondary malignancy of the pancreas.

Science.gov (United States)

Hung, Jui-Hsia; Wang, Shin-E; Shyr, Yi-Ming; Su, Cheng-Hsi; Chen, Tien-Hua; Wu, Chew-Wun

2012-01-01

This study tried to clarify the role of pancreatic resection in the treatment of secondary malignancy with metastasis or local invasion to the pancreas in terms of surgical risk and survival benefit. Data of secondary malignancy of the pancreas from our 19 patients and cases reported in the English literature were pooled together for analysis. There were 329 cases of resected secondary malignancy of the pancreas, including 241 cases of metastasis and 88 cases of local invasion. The most common primary tumor metastatic to the pancreas and amenable to resection was renal cell carcinoma (RCC) (73.9%). More than half (52.3%) of the primary cancers with local invasion to the pancreas were colon cancer, and nearly half (40.9%) were stomach cancer. The median metastatic interval was 84 months (7 years) for overall primary tumors and 108 months (9 years) for RCC. The 5-year survival for secondary malignancy of the pancreas after resection was 61.1% for metastasis and 58.9% for local invasion, with 72.8% for RCC metastasis, 69.0% for colon cancer, and 43.8% for stomach cancer with local invasion to the pancreas. Pancreatic resection should not be precluded for secondary malignancy of the pancreas because long-term survival could be achieved with acceptable surgical risk in selected patients.

Pancreas preserving total duodenectomy for complex duodenal injury.

Science.gov (United States)

Wig, Jai Dev; Kudari, Ashwinikumar; Yadav, Thakur Deen; Doley, Rudra Prasad; Bharathy, Kishore Gurumoorthy Subramanya; Kalra, Naveen

2009-07-06

To assess the feasibility and safety of a pancreas-preserving total duodenectomy in the management of severe duodenal injury caused by abdominal trauma. Two patients with both extensive injury of the duodenum and diffuse peritonitis underwent pancreas preserving total duodenectomy at our tertiary care centre. These two young male patients (age 20 and 22 years) presented 2 days and 6 hours respectively following blunt abdominal trauma. The duodenum was almost completely separated from the pancreas. Ampulla was seen as a button on the pancreas. Following total duodenectomy, reconstruction was performed by suturing the jejunum to the head of the pancreas anteriorly and posteriorly away from the ampulla (invagination of the pancreas into the jejunum). There were no complications attributable to the procedure. Both patients are well on follow up. A Pancreas-preserving total duodenectomy offers a safe alternative to the Whipple procedure in managing complex duodenal injury. This procedure avoids unnecessary resection of the adjacent pancreas and anastomosis to undilated hepatic and pancreatic ducts.

Clinical evaluation of computed tomography of the pancreas

International Nuclear Information System (INIS)

Miura, Takashi; Nakao, Morio; Takayasu, Yukio; Inamoto, Kazuo; Yamazaki, Hideo

1980-01-01

The pancreas was observed from many directions on conventional CT images and reconstructed coronal and sagittal tomograms. Absorbed values of x-ray in the pancreas were also counted by setting ROI on conventional CT images. The subjects were 37 patients with pancreatic diseases or normal pancreas. Equipments used were Somatom SD and Evaluskop for analysis of images. Slice width and feed for reconstruction of CT images were 4 mm and 3 mm, respectively. Absorbed values of x-ray was significantly lower in patients with pancreatic carcinoma than in patients with normal pancreas. Slightly low absorbed values of x-ray in pancreas tail could suggest small carcinoma of pancreas even when CT images could not visualize it clearly. There was not a significant difference in absorbed values between chronic pancreatitis and normal pancreas, but their variations were big. Observation of the pancreas from many directions on reconstructed CT images were very useful for the diagnosis of pancreatic diseases. (Tsunoda, M.)

A novel subcutaneous site of islet transplantation superior to the liver.

Science.gov (United States)

Yasunami, Yohichi; Nakafusa, Yuki; Nitta, Naoyoshi; Nakamura, Masafumi; Goto, Masafumi; Ono, Junko; Taniguchi, Masaru

2018-03-08

Islet transplantation is an attractive treatment for patients with insulin-dependent diabetes mellitus, and currently the liver is the favored transplantation site. However, an alternative site is desirable because of the low efficiency of hepatic transplantation, requiring 2-3 donors for a single recipient, and because the transplanted islets cannot be accessed or retrieved. We developed a novel procedure of islet transplantation to the inguinal subcutaneous white adipose tissue (ISWAT) of mice and described functional and morphological characteristics of transplanted syngeneic islets. Also, it was determined whether islet allograft rejection in the ISWAT can be prevented by immunosuppressive agents. Furthermore, it was examined whether human islets function when grafted in this particular site of immune-deficient mice. In this site, transplanted islets are engrafted as clusters and function to reverse STZ-induced diabetes in mice. Importantly, transplanted islets can be visualized by CT and are easily retrievable, and allograft rejection is preventable by blockade of co-stimulatory signals. Of much importance, the efficiency of islet transplantation in this site is superior to the liver, in which hyperglycemia of diabetic recipient mice is ameliorated after transplantation of 200 syngeneic islets (the islet number yielded from 1 mouse pancreas) to the ISWAT but not to the liver. Furthermore, human islets transplanted in this particular site function to reverse diabetes in immune-deficient mice. Thus, the ISWAT is superior to the liver as the site of islet transplantation, which may lead to improved outcome of clinical islet transplantation.

Expression pattern of thymosin beta 4 in the adult human liver

Directory of Open Access Journals (Sweden)

S. Nemolato

2011-09-01

Full Text Available Thymosin beta-4 (Tβ4 is a member of beta-thymosins, a family of small peptides involved in polymerization of G-actin, and in many critical biological processes including apoptosis, cell migration, angiogenesis, and fibrosis. Previous studies in the newborn liver did not reveal any significant reactivity for Tβ4 during the intrauterine life. The aim of the present study was to investigate by immunohistochemistry Tβ4 expression in the adult normal liver. Thirty-five human liver samples, including 11 needle liver biopsies and 24 liver specimens obtained at autopsy, in which no pathological change was detected at the histological examination, were immunostained utilizing an anti-Tβ4 commercial antibody. Tβ4 was detected in the hepatocytes of all adult normal livers examined. A zonation of Tβ4 expression was evident in the vast majority of cases. Immunostaining was preferentially detected in zone 3, while a minor degree of reactivity was detected in periportal hepatocytes (zone 1. At higher power, Tβ4-reactive granules appeared mainly localized at the biliary pole of hepatocytes. In cases with a strong immunostaining, even perinuclear areas and the sinusoidal pole of hepatocytes appeared interested by immunoreactivity for Tβ4. The current work first evidences a strong diffuse expression of Tβ4 in the adult human liver, and adds hepatocytes to the list of human cells able to synthesize large amounts of Tβ4 in adulthood. Moreover, Tβ4 should be added to the liver proteins characterized by a zonate expression pattern, in a descending gradient from the terminal vein to the periportal areas of the liver acinus. Identifying the intimate role played by this peptide intracellularly and extracellularly, in physiology and in different liver diseases, is a major challenge for future research focusing on Tβ4.

Recellularization of rat liver: An in vitro model for assessing human drug metabolism and liver biology.

Directory of Open Access Journals (Sweden)

Matthew J Robertson

Full Text Available Liver-like organoids that recapitulate the complex functions of the whole liver by combining cells, scaffolds, and mechanical or chemical cues are becoming important models for studying liver biology and drug metabolism. The advantages of growing cells in three-dimensional constructs include enhanced cell-cell and cell-extracellular matrix interactions and preserved cellular phenotype including, prevention of de-differentiation. In the current study, biomimetic liver constructs were made via perfusion decellularization of rat liver, with the goal of maintaining the native composition and structure of the extracellular matrix. We optimized our decellularization process to produce liver scaffolds in which immunogenic residual DNA was removed but glycosaminoglycans were maintained. When the constructs were recellularized with rat or human liver cells, the cells remained viable, capable of proliferation, and functional for 28 days. Specifically, the cells continued to express cytochrome P450 genes and maintained their ability to metabolize a model drug, midazolam. Microarray analysis showed an upregulation of genes involved in liver regeneration and fibrosis. In conclusion, these liver constructs have the potential to be used as test beds for studying liver biology and drug metabolism.

Application of chimeric mice with humanized liver for study of human-specific drug metabolism.

Science.gov (United States)

Bateman, Thomas J; Reddy, Vijay G B; Kakuni, Masakazu; Morikawa, Yoshio; Kumar, Sanjeev

2014-06-01

Human-specific or disproportionately abundant human metabolites of drug candidates that are not adequately formed and qualified in preclinical safety assessment species pose an important drug development challenge. Furthermore, the overall metabolic profile of drug candidates in humans is an important determinant of their drug-drug interaction susceptibility. These risks can be effectively assessed and/or mitigated if human metabolic profile of the drug candidate could reliably be determined in early development. However, currently available in vitro human models (e.g., liver microsomes, hepatocytes) are often inadequate in this regard. Furthermore, the conduct of definitive radiolabeled human ADME studies is an expensive and time-consuming endeavor that is more suited for later in development when the risk of failure has been reduced. We evaluated a recently developed chimeric mouse model with humanized liver on uPA/SCID background for its ability to predict human disposition of four model drugs (lamotrigine, diclofenac, MRK-A, and propafenone) that are known to exhibit human-specific metabolism. The results from these studies demonstrate that chimeric mice were able to reproduce the human-specific metabolite profile for lamotrigine, diclofenac, and MRK-A. In the case of propafenone, however, the human-specific metabolism was not detected as a predominant pathway, and the metabolite profiles in native and humanized mice were similar; this was attributed to the presence of residual highly active propafenone-metabolizing mouse enzymes in chimeric mice. Overall, the data indicate that the chimeric mice with humanized liver have the potential to be a useful tool for the prediction of human-specific metabolism of xenobiotics and warrant further investigation.

Phosphorus-31 spectroscopic imaging of the human liver

International Nuclear Information System (INIS)

Biran, M.; Raffard, G.; Canioni, P.; Kien, P.

1993-01-01

During the last decade, progresses in the field of nuclear magnetic resonance spectroscopy (M.R.S.), have allowed the metabolic studies of complex biological systems. Since the coming out of whole body magnets, clinical applications are possible; they utilize magnetic field gradients coupled with selective pulse sequences. Study of the phosphorylated metabolism of human liver can be performed with sequences as ISIS, FROGS or 1D-CSI. But they present some disadvantages (for instance contamination by phosphocreatine from muscle). In the present work, we have studied the human liver in vivo by 31 P spectroscopic imaging. Several spectra could be acquired with only one acquisition. This study has needed the building of radiofrequency coils (surface coils), specially designed for liver observation (15 cm diameter 31 P coil and 19 cm diameter proton coil, both transmitter and receiver coils). Preliminary studies have been done on a phantom followed by in vivo measurements on healthy subject livers. We have obtained localized 31 P N.M.R. spectra corresponding to different voxels within the hepatic tissue. The conditions of acquisition of spectra and the problems related to the saturation of phosphorylated metabolite signals (in particular phosphodiesters) are discussed. (author). 5 figs., 15 refs

Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells

Directory of Open Access Journals (Sweden)

Takanori Takebe

2017-12-01

Full Text Available Summary: Organoid technology provides a revolutionary paradigm toward therapy but has yet to be applied in humans, mainly because of reproducibility and scalability challenges. Here, we overcome these limitations by evolving a scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC. By conducting massive “reverse” screen experiments, we identified three progenitor populations that can effectively generate liver buds in a highly reproducible manner: hepatic endoderm, endothelium, and septum mesenchyme. Furthermore, we achieved human scalability by developing an omni-well-array culture platform for mass producing homogeneous and miniaturized liver buds on a clinically relevant large scale (>108. Vascularized and functional liver tissues generated entirely from iPSCs significantly improved subsequent hepatic functionalization potentiated by stage-matched developmental progenitor interactions, enabling functional rescue against acute liver failure via transplantation. Overall, our study provides a stringent manufacturing platform for multicellular organoid supply, thus facilitating clinical and pharmaceutical applications especially for the treatment of liver diseases through multi-industrial collaborations. : With the goal of clinical translation of liver bud transplant therapy, Takebe et al. established a massive organoid production platform from endoderm, endothelial, and mesenchymal progenitor populations specified entirely from human iPSCs, reproducibly demonstrating functionality both in vitro and in vivo. Keywords: iPSC, liver bud, organoid, transplantation, self-organization, endothelial, mesenchymal, liver failure, clinical grade

Cellular and molecular mechanisms coordinating pancreas development.

Science.gov (United States)

Bastidas-Ponce, Aimée; Scheibner, Katharina; Lickert, Heiko; Bakhti, Mostafa

2017-08-15

The pancreas is an endoderm-derived glandular organ that participates in the regulation of systemic glucose metabolism and food digestion through the function of its endocrine and exocrine compartments, respectively. While intensive research has explored the signaling pathways and transcriptional programs that govern pancreas development, much remains to be discovered regarding the cellular processes that orchestrate pancreas morphogenesis. Here, we discuss the developmental mechanisms and principles that are known to underlie pancreas development, from induction and lineage formation to morphogenesis and organogenesis. Elucidating such principles will help to identify novel candidate disease genes and unravel the pathogenesis of pancreas-related diseases, such as diabetes, pancreatitis and cancer. © 2017. Published by The Company of Biologists Ltd.

Monocytes infiltrate the pancreas via the MCP-1/CCR2 pathway and differentiate into stellate cells.

Directory of Open Access Journals (Sweden)

Kazuko Ino

Full Text Available Recent studies have shown that monocytes possess pluripotent plasticity. We previously reported that monocytes could differentiate into hepatic stellate cells. Although stellate cells are also present in the pancreas, their origin remains unclear. An accumulation of enhanced green fluorescent protein (EGFP(+CD45(- cells was observed in the pancreases and livers of chimeric mice, which were transplanted with a single hematopoietic stem cell isolated from EGFP-transgenic mice and treated with carbon tetrachloride (CCl4. Because the vast majority of EGFP(+CD45(- cells in the pancreas expressed stellate cell-associated antigens such as vimentin, desmin, glial fibrillary acidic protein, procollagen-I, and α-smooth muscle actin, they were characterized as pancreatic stellate cells (PaSCs. EGFP(+ PaSCs were also observed in CCl4-treated mice adoptively transferred with monocytes but not with other cell lineages isolated from EGFP-transgenic mice. The expression of monocyte chemoattractant protein-1 (MCP-1 and angiotensin II (Ang II increased in the pancreas of CCl4-treated mice and their respective receptors, C-C chemokine receptor 2 (CCR2 and Ang II type 1 receptor (AT1R, were expressed on Ly6C(high monocytes isolated from EGFP-transgenic mice. We examined the effect of an AT1R antagonist, irbesartan, which is also a CCR2 antagonist, on the migration of monocytes into the pancreas. Monocytes migrated toward MCP-1 but not Ang II in vitro. Irbesartan inhibited not only their in vitro chemotaxis but also in vivo migration of adoptively transferred monocytes from peripheral blood into the pancreas. Irbesartan treatment significantly reduced the numbers of EGFP(+F4/80(+CCR2(+ monocytic cells and EGFP(+ PaSCs in the pancreas of CCl4-treated chimeric mice receiving EGFP(+ bone marrow cells. A specific CCR2 antagonist RS504393 inhibited the occurrence of EGFP(+ PaSCs in injured mice. We propose that CCR2(+ monocytes migrate into the pancreas possibly via the

Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis

Science.gov (United States)

Huch, Meritxell; Bonfanti, Paola; Boj, Sylvia F; Sato, Toshiro; Loomans, Cindy J M; van de Wetering, Marc; Sojoodi, Mozhdeh; Li, Vivian S W; Schuijers, Jurian; Gracanin, Ana; Ringnalda, Femke; Begthel, Harry; Hamer, Karien; Mulder, Joyce; van Es, Johan H; de Koning, Eelco; Vries, Robert G J; Heimberg, Harry; Clevers, Hans

2013-01-01

Lgr5 marks adult stem cells in multiple adult organs and is a receptor for the Wnt-agonistic R-spondins (RSPOs). Intestinal, stomach and liver Lgr5+ stem cells grow in 3D cultures to form ever-expanding organoids, which resemble the tissues of origin. Wnt signalling is inactive and Lgr5 is not expressed under physiological conditions in the adult pancreas. However, we now report that the Wnt pathway is robustly activated upon injury by partial duct ligation (PDL), concomitant with the appearance of Lgr5 expression in regenerating pancreatic ducts. In vitro, duct fragments from mouse pancreas initiate Lgr5 expression in RSPO1-based cultures, and develop into budding cyst-like structures (organoids) that expand five-fold weekly for >40 weeks. Single isolated duct cells can also be cultured into pancreatic organoids, containing Lgr5 stem/progenitor cells that can be clonally expanded. Clonal pancreas organoids can be induced to differentiate into duct as well as endocrine cells upon transplantation, thus proving their bi-potentiality. PMID:24045232

MR imaging of pancreas in cystic fibrosis

International Nuclear Information System (INIS)

Murayama, S.; Robinson, A.E.; Mulvihill, D.M.; Stallworth, J.M.; Goyco, P.G.; Beckerman, R.C.; Hines, M.R.

1990-01-01

The pancreatic regions of 18 patients with cystic fibrosis were analyzed with a 1.5 Tesla MR unit. Signal intensity of the pancreas was correlated with clinical data and ultrasound. A hyperintense pancreas on T1-weighted image was consistent with fatty replacement of pancreatic insufficiency. A pancreas of normal soft tissue intensity was found in two asymptomatic and one symptomatic patient. A very hypointense pancreas on any pulse sequence was considered to be an intermediate stage of pancreatic degeneration. (orig.)

Imaging of the human heart after administration of l-(N-13)glutamate

International Nuclear Information System (INIS)

Gelbard, A.S.; Benua, R.S.; Reiman, R.E.; McDonald, J.M.; Vomero, J.J.; Laughlin, J.S.

1980-01-01

In normal volunteers and cancer patients, studies using L-(N-13)glutamate as an imaging agent showed localization of N-13 activity in the heart. Other organs that were well visualized include the liver, pancreas, and salivary glands. The concentration of N-13 activity in the human heart could not be predicted from previous studies involving myocardial uptake in dogs and rodents after administration of L-(N-13)glutamate

Comparative functional scintigraphic and angiographic examination in pancreas diseases

International Nuclear Information System (INIS)

Mendizov, A.; Brilski, V.; Bozhiyanov, A.; Romanova, A.; Mardzhanov, I.; Glavincheva, I.; Meditsinska Akademiya, Sofia

1979-01-01

Pancreas scintigraphy with 75 seleno-methionine, pancreocimine-secretine test and selective abdominal angiography was carried out in patients with chronic pancreatitis, pancreas carcinoma and subjects without any pancreas diseases. Scintigraphic changes in pancreas was found in 95,6 per cent of the patients with chronic pancreatitis (136 patients), in 92 per cent of them with pancreas carcinoma (25 patients) and in 53,4 per cent from the subjects without pancreas diseases (30 examined). Pathological changes in pancreatic secretion was found in 93,4 per cent of the patients with chronic pancreatitis (105 patients), in 93,8 per cent of the subjects with pancreas carcinoma (32 patients) and only in 3,9 per cent from the examined without pancreatic diseases. The angiographic examination is informative mainly in case of tumours and cysts of the pancreas. The diagnostic potentialities of the separate methods for pancreas examination were critically assessed. The basic diagnostic problems in pancreas diseases are solved to a great extent with the combined examination with scintigraphy pancreocimine test and angiography (76 patients). (author)

Well differentiated endocrine carcinomas of the pancreas

Directory of Open Access Journals (Sweden)

Čolović Radoje

2011-01-01

Full Text Available Introduction. For the difference from poorly differentiated, well differentiated endocrine carcinomas of the pancreas are the tumours in whom with aggressive surgery and chemotherapy fair results can be achieved. Objective. The aim of the study was to point out the importance of such treatment. Methods. Over a 6-year period eight patients (seven female and one male of average age 51 years (ranging from 23 to 71 years were operated on for well differentiated endocrine carcinoma: six of the head and two of the tail of the pancreas. There were two functional and six nonfunctional tumours. Pain in the upper part of the abdomen in seven, mild loss in weight in two, strong heartburn in two, obstructive jaundice in three, diarrhoea in one, sudden massive bleeding from gastric varicosities due to prehepatic portal hypertension caused by pancreatic head tumour in one, and bruise in one patient were registered preoperatively. US and CT in all, angiography in one, octreoscan in two and PET scan in one patient were performed. Whipple’s procedure was performed in six and distal pancreatectomy in two patients, as well as systemic lymphadenectomy in all and excision of liver secondary tumours in two patients. In the patient with massive gastric bleeding a total gastrectomy was performed first, followed by Whipple’s procedure a month later. Results. R0 resection was achieved in all patients. Lymph nodes metastases were found in six patients. Six patients were given chemotherapy. One patient died 3 years after surgery, seven are still alive, on average 2.5 years. A local recurrence after distal pancreatectomy that occurred 5 years after surgery was successfully reresected and the patient is on peptide-receptor radiotherapy. In other six patients there were no local recurence or distant metastases. Conclusion. With aggressive surgery and chemotherapy fair results can be achieved in well differentiated endocrine carcinomas of the pancreas.

Liver Effects of Clinical Drugs Differentiated in Human Liver Slices

Directory of Open Access Journals (Sweden)

Alison E. M. Vickers

2017-03-01

Full Text Available Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM, diclofenac (DCF, 1 mM and etomoxir (ETM, 100 μM. Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM and cyclosporin A (CSA, 10 μM, while GSH was affected more than ATP by methimazole (MMI, 500 μM, terbinafine (TBF, 100 μM, and carbamazepine (CBZ 100 μM. Oxidative stress genes were affected by TBF (18%, CBZ, APAP, and ETM (12%–11%, and mitochondrial genes were altered by CBZ, APAP, MMI, and ETM (8%–6%. Apoptosis genes were affected by DCF (14%, while apoptosis plus necrosis were altered by APAP and ETM (15%. Activation of oxidative stress, mitochondrial energy, heat shock, ER stress, apoptosis, necrosis, DNA damage, immune and inflammation genes ranked CSA (75%, ETM (66%, DCF, TBF, MMI (61%–60%, APAP, CBZ (57%–56%, and DTL (48%. Gene changes in fatty acid metabolism, cholestasis, immune and inflammation were affected by DTL (51%, CBZ and ETM (44%–43%, APAP and DCF (40%–38%, MMI, TBF and CSA (37%–35%. This model advances multiple dosing in a human ex vivo model, plus functional markers and gene profile markers of drug induced human liver side-effects.

Pretargeting vs. direct targeting of human betalox5 islet cells subcutaneously implanted in mice using an anti-human islet cell antibody

International Nuclear Information System (INIS)

Liu Guozheng; Dou Shuping; Akalin, Ali; Rusckowski, Mary; Streeter, Philip R.; Shultz, Leonard D.; Greiner, Dale L.

2012-01-01

Introduction: We previously demonstrated MORF/cMORF pretargeting of human islets and betalox 5 cells (a human beta cell line) transplanted subcutaneously in mice with the anti-human islet antibody, HPi1. We now compare pretargeting with direct targeting in the beta cell transplant model to evaluate the degree to which target/non-target (T/NT) ratios may be improved by pretargeting. Methods: Specific binding of an anti-human islet antibody HPi1 to the beta cells transplanted subcutaneously in mice was examined against a negative control antibody. We then compared pretargeting by MORF-HPi1 plus 111 In-labeled cMORF to direct targeting by 111 In-labeled HPi1. Results: HPi1 binding to betalox5 human cells in the transplant was shown by immunofluorescence. Normal organ 111 In backgrounds by pretargeting were always lower, although target accumulations were similar. More importantly, the transplant to pancreas and liver ratios was, respectively, 26 and 10 by pretargeting as compared to 9 and 0.6 by direct targeting. Conclusions: Pretargeting greatly improves the T/NT ratios, and based on the estimated endocrine to exocrine ratio within a pancreas, pretargeting may be approaching the sensitivity required for successful imaging of human islets within this organ.

Pancreas retransplantation: a second chance for diabetic patients?

Science.gov (United States)

Buron, Fanny; Thaunat, Olivier; Demuylder-Mischler, Sandrine; Badet, Lionel; Brunet, Maria; Ber, Charles-Eric; Thivolet, Charles; Martin, Xavier; Berney, Thierry; Morelon, Emmanuel

2013-01-27

If pancreas transplantation is a validated alternative for type 1 diabetic patients with end-stage renal disease, the management of patients who have lost their primary graft is poorly defined. This study aims at evaluating pancreas retransplantation outcome. Between 1976 and 2008, 569 pancreas transplantations were performed in Lyon and Geneva, including 37 second transplantations. Second graft survival was compared with primary graft survival of the same patients and the whole population. Predictive factors of second graft survival were sought. Patient survival and impact on kidney graft function and survival were evaluated. Second pancreas survival of the 17 patients transplanted from 1995 was close to primary graft survival of the whole population (71% vs. 79% at 1 year and 59% vs. 69% at 5 years; P=0.5075) and significantly better than their first pancreas survival (71% vs. 29% at 1 year and 59% vs. 7% at 5 years; P=0.0008) regardless of the cause of first pancreas loss. The same results were observed with all 37 retransplantations. Survival of second simultaneous pancreas and kidney transplantations was better than survival of second pancreas after kidney. Patient survival was excellent (89% at 5 years). Pancreas retransplantation had no impact on kidney graft function and survival (100% at 5 years). Pancreas retransplantation is a safe procedure with acceptable graft survival that should be proposed to diabetic patients who have lost their primary graft.

A Study on Pancreas Scanning with Selenium75-Selenomethionine

International Nuclear Information System (INIS)

Shin, Hyun Chan; Toh, Sang Hee; Ra, Woo Youn; Suh, Chul Sung

1968-01-01

Radiographic visualization of the pancreas is a difficult problem, but the direct visualization of the pancreas is possible by the injection of the amino-acid methionine tagged with selenium 75 (Se 75 ). In order to know the diagnostic value of pancreas scanning, scans were performed on 23 cases using selenium 75 -Selenomethionine. These cases were also given egg white, probanthine and morphine. 1) Good visualization of the pancreas scanning was observed on 19 cases, presumably with normal pancreas. 2) A case which showed diffusely decreased uptake on pancreas scanning was proven to have lesions in the bile duct and the gall bladder. 3) Of those two cases which showed localized cold area, one had pancreas cyst and the other one was not explored. 4) A case which showed no visualization of the pancreas was proven to have pancreatic carcinoma. 5) Two cases which showed widened duodenal loop by upper gastro-intestinal series revealed normal pancreas scanning, and no pancreatic disease was found in both cases.

Completion of hepatitis C virus replication cycle in heterokaryons excludes dominant restrictions in human non-liver and mouse liver cell lines.

Directory of Open Access Journals (Sweden)

Anne Frentzen

2011-04-01

Full Text Available Hepatitis C virus (HCV is hepatotropic and only infects humans and chimpanzees. Consequently, an immunocompetent small animal model is lacking. The restricted tropism of HCV likely reflects specific host factor requirements. We investigated if dominant restriction factors expressed in non-liver or non-human cell lines inhibit HCV propagation thus rendering these cells non-permissive. To this end we explored if HCV completes its replication cycle in heterokaryons between human liver cell lines and non-permissive cell lines from human non-liver or mouse liver origin. Despite functional viral pattern recognition pathways and responsiveness to interferon, virus production was observed in all fused cells and was only ablated when cells were treated with exogenous interferon. These results exclude that constitutive or virus-induced expression of dominant restriction factors prevents propagation of HCV in these cell types, which has important implications for HCV tissue and species tropism. In turn, these data strongly advocate transgenic approaches of crucial human HCV cofactors to establish an immunocompetent small animal model.

A Case of Successful Simultaneous Pancreas-Kidney Transplantation Using the Injured Pancreas Graft.

Science.gov (United States)

Miyagi, S; Shimizu, K; Miyazawa, K; Nakanishi, W; Hara, Y; Tokodai, K; Nakanishi, C; Satomi, S; Goto, M; Unno, M; Kamei, T

2017-12-01

Graft injuries sometimes occur and may cause complications such as the leakage of pancreatic secretions, which is often lethal. We report our experience of a case of successful simultaneous pancreas-kidney transplantation using injured pancreas graft. The recipient was a 57-year-old woman with type 1 diabetes mellitus, and the donor was a 30-year-old man with a brain injury. In the donation, the pancreas parenchyma, splenic artery, and gastroduodenal artery were injured iatrogenically. We therefore reconstructed these arteries using vessel grafts and then performed simultaneous pancreas-kidney transplantation. Five days after transplantation, we noted a high titer of amylase in the ascites; therefore, we performed an urgent laparotomy. The origin of the amylase was the injured pancreatic parenchyma, and continued washing and drainage were carried out. We reconstructed the duodenojejunostomy using the Roux-en-Y technique to separate the passage of food from the pancreas graft to prevent injury to other organs due to exposure to pancreatic secretions. Thereafter, we inserted a decompression tube into the anastomosis thorough the blind end of the jejunum. Finally, we inserted 3 drainage tubes for lavage. Following this procedure, the patient recovered gradually and no longer required hemodialysis and insulin therapy. She was discharged from our hospital 56 days after transplantation. The restoration of the injured graft was possible by management of pancreatic secretions and use of the donor's vessel grafts. Shortage of donors is a problem throughout the world; thus, it is important to use injured grafts for transplantation if possible. Copyright © 2017 Elsevier Inc. All rights reserved.

Dipeptidyl peptidase-4 greatly contributes to the hydrolysis of vildagliptin in human liver.

Science.gov (United States)

Asakura, Mitsutoshi; Fujii, Hideaki; Atsuda, Koichiro; Itoh, Tomoo; Fujiwara, Ryoichi

2015-04-01

The major metabolic pathway of vildagliptin in mice, rats, dogs, and humans is hydrolysis at the cyano group to produce a carboxylic acid metabolite M20.7 (LAY151), whereas the major metabolic enzyme of vildagliptin has not been identified. In the present study, we determined the contribution rate of dipeptidyl peptidase-4 (DPP-4) to the hydrolysis of vildagliptin in the liver. We performed hydrolysis assay of the cyano group of vildagliptin using mouse, rat, and human liver samples. Additionally, DPP-4 activities in each liver sample were assessed by DPP-4 activity assay using the synthetic substrate H-glycyl-prolyl-7-amino-4-methylcoumarin (Gly-Pro-AMC). M20.7 formation rates in liver microsomes were higher than those in liver cytosol. M20.7 formation rate was significantly positively correlated with the DPP-4 activity using Gly-Pro-AMC in liver samples (r = 0.917, P vildagliptin hydrolysis in the liver. Additionally, we established stable single expression systems of human DPP-4 and its R623Q mutant, which is the nonsynonymous single-nucleotide polymorphism of human DPP-4, in human embryonic kidney 293 (HEK293) cells to investigate the effect of R623Q mutant on vildagliptin-hydrolyzing activity. M20.7 formation rate in HEK293 cells expressing human DPP-4 was significantly higher than that in control HEK293 cells. Interestingly, R623Q mutation resulted in a decrease of the vildagliptin-hydrolyzing activity. Our findings might be useful for the prediction of interindividual variability in vildagliptin pharmacokinetics. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Human plasma metabolic profiles of benzydamine, a flavin-containing monooxygenase probe substrate, simulated with pharmacokinetic data from control and humanized-liver mice.

Science.gov (United States)

Yamazaki-Nishioka, Miho; Shimizu, Makiko; Suemizu, Hiroshi; Nishiwaki, Megumi; Mitsui, Marina; Yamazaki, Hiroshi

2018-02-01

1. Benzydamine is used clinically as a nonsteroidal anti-inflammatory drug in oral rinses and is employed in preclinical research as a flavin-containing monooxygenase (FMO) probe substrate. In this study, plasma concentrations of benzydamine and its primary N-oxide and N-demethylated metabolites were investigated in control TK-NOG mice, in humanized-liver mice, and in mice whose liver cells had been ablated with ganciclovir. 2. Following oral administration of benzydamine (10 mg/kg) in humanized-liver TK-NOG mice, plasma concentrations of benzydamine N-oxide were slightly higher than those of demethyl benzydamine. In contrast, in control and ganciclovir-treated TK-NOG mice, concentrations of demethyl benzydamine were slightly higher than those of benzydamine N-oxide. 3. Simulations of human plasma concentrations of benzydamine and its N-oxide were achieved using simplified physiologically based pharmacokinetic models based on data from control TK-NOG mice and from reported benzydamine concentrations after low-dose administration in humans. Estimated clearance rates based on data from humanized-liver and ganciclovir-treated TK-NOG mice were two orders magnitude high. 4. The pharmacokinetic profiles of benzydamine were different for control and humanized-liver TK-NOG mice. Humanized-liver mice are generally accepted human models; however, drug oxidation in mouse kidney might need to be considered when probe substrates undergo FMO-dependent drug oxidation in mouse liver and kidney.

Human germline hedgehog pathway mutations predispose to fatty liver.

Science.gov (United States)

Guillen-Sacoto, Maria J; Martinez, Ariel F; Abe, Yu; Kruszka, Paul; Weiss, Karin; Everson, Joshua L; Bataller, Ramon; Kleiner, David E; Ward, Jerrold M; Sulik, Kathleen K; Lipinski, Robert J; Solomon, Benjamin D; Muenke, Maximilian

2017-10-01

Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations that affect this pathway. Patients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD. A combined mouse model of Hh signaling attenuation (Gli2 heterozygous null: Gli2 +/- ) and diet-induced NAFLD was used to examine aspects of NAFLD and hepatic gene expression profiles, including molecular markers of hepatic fibrosis and inflammation. Patients with HPE had a higher prevalence of liver steatosis compared to the general population, independent of obesity. Exposure of Gli2 +/- mice to fatty liver-inducing diets resulted in increased liver steatosis compared to wild-type mice. Similar to humans, this effect was independent of obesity in the mutant mice and was associated with decreased expression of pro-fibrotic and pro-inflammatory genes, and increased expression of PPARγ, a potent anti-fibrogenic and anti-inflammatory regulator. Interestingly, tumor suppressors p53 and p16INK4 were found to be downregulated in the Gli2 +/- mice exposed to a high-fat diet. Our results indicate that germline mutations disrupting Hh signaling promotes liver steatosis, independent of obesity, with reduced fibrosis. While Hh signaling inhibition has been associated with a better NAFLD prognosis, further studies are required to evaluate the long-term effects of mutations affecting this pathway. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is characterized by excess fat deposition in the liver predominantly due to high calorie intake and a sedentary lifestyle. NAFLD progression is usually accompanied by activation of the Sonic hedgehog (SHH) pathway leading to fibrous

Isolation and characterization of adult human liver progenitors from ischemic liver tissue derived from therapeutic hepatectomies.

Science.gov (United States)

Stachelscheid, Harald; Urbaniak, Thomas; Ring, Alexander; Spengler, Berlind; Gerlach, Jörg C; Zeilinger, Katrin

2009-07-01

Recent evidence suggests that progenitor cells in adult tissues and embryonic stem cells share a high resistance to hypoxia and ischemic stress. To study the ischemic resistance of adult liver progenitors, we characterized remaining viable cells in human liver tissue after cold ischemic treatment for 24-168 h, applied to the tissue before cell isolation. In vitro cultures of isolated cells showed a rapid decline of the number of different cell types with increasing ischemia length. After all ischemic periods, liver progenitor-like cells could be observed. The comparably small cells exhibited a low cytoplasm-to-nucleus ratio, formed densely packed colonies, and showed a hepatobiliary marker profile. The cells expressed epithelial cell adhesion molecule, epithelial-specific (CK8/18) and biliary-specific (CK7/19) cytokeratins, albumin, alpha-1-antitrypsin, cytochrome-P450 enzymes, as well as weak levels of hepatocyte nuclear factor-4 and gamma-glutamyl transferase, but not alpha-fetoprotein or Thy-1. In vitro survival and expansion was facilitated by coculture with mouse embryonic fibroblasts. Hepatic progenitor-like cells exhibit a high resistance to ischemic stress and can be isolated from human liver tissue after up to 7 days of ischemia. Ischemic liver tissue from various sources, thought to be unsuitable for cell isolation, may be considered as a prospective source of hepatic progenitor cells.

Expression and kinetic properties of a recombinant 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzyme of human liver.

Science.gov (United States)

Deyashiki, Y; Tamada, Y; Miyabe, Y; Nakanishi, M; Matsuura, K; Hara, A

1995-08-01

Human liver cytosol contains multiple forms of 3 alpha-hydroxysteroid dehydrogenase and dihydrodiol dehydrogenase with hydroxysteroid dehydrogenase activity, and multiple cDNAs for the enzymes have been cloned from human liver cDNA libraries. To understand the relationship of the multiple enzyme froms to the genes, a cDNA, which has been reported to code for an isoenzyme of human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase, was expressed in Escherichia coli. The recombinant enzyme showed structural and functional properties almost identical to those of the isoenzyme purified from human liver. In addition, the recombinant isoenzyme efficiently reduced 5 alpha-dihydrotestosterone and 5 beta-dihydrocortisone, the known substrates of human liver 3 alpha-hydroxysteroid dehydrogenase and chlordecone reductase previously purified, which suggests that these human liver enzymes are identical. Furthermore, the steady-state kinetic data for NADP(+)-linked (S)-1-indanol oxidation by the recombinant isoenzyme were consistent with a sequential ordered mechanism in which NADP+ binds first. Phenolphthalein inhibited this isoenzyme much more potently than it did the other human liver dihydrodiol dehydrogenases, and was a competitive inhibitor (Ki = 20 nM) that bound to the enzyme-NADP+ complex.

The State of Pancreatobiliary System and Intestinal Microflora in Children with Nonalcoholic Fatty Liver Disease

Directory of Open Access Journals (Sweden)

N.Yu. Zavgorodnya

2016-11-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD combines with a variety of liver pathologies, including hepatic steatosis, nonalcoholic steatohepatitis, fibrosis and cirrhosis, and acts as hepatic manifestation of metabolic syndrome. Not only the liver is a target organ in the formation of metabolic syndrome: also exist a possibility of gallbladder, pancreas and biliary tract steatosis. Fatty infiltration of the pancreatobiliary system associates with disturbance of digestive processes that promotes dysbiotic changes and intestinal disorders. Changes in intestinal microbiota, in turn, may induce systemic inflammatory response and promote NAFLD development and progression. Objective: to explore the structural and functional state of the pancreatobiliary system and changes of the enteric microflora in children with NAFLD. Methods. In 34 children with disorders of the gastrointestinal tract, we have determined controlled attenuation parameter by means of FibroScan. Assessment of functional status of biliary tract was performed using an ultrasound examination of the abdominal organs with test meal in order to determine gallbladder contractility and the sphincter of Oddi function. To characterize the state of the enteric microbiota, there was carried out a hydrogen breath test with glucose or lactose loading. Children were divided into groups according to the the transient elastography of the liver (FibroScan: the control group was represented by 21 patients without liver steatosis, the main group — 13 patients with liver steatosis. Results. Children with nonalcoholic fatty liver disease had signs of not only liver pathology, but also of the bile ducts and the pancreas. Biliary tract dysfunction in patients with NAFLD more often manifested as hypotension of the sphincter of Oddi and the gallbladder hypokinesia. Lesions of the pancreas function in children with NAFLD can be explained by the sphincter of Oddi disorders and manifestations of pancreatic

Development of Murine Cyp3a Knockout Chimeric Mice with Humanized Liver.

Science.gov (United States)

Kato, Kota; Ohbuchi, Masato; Hamamura, Satoko; Ohshita, Hiroki; Kazuki, Yasuhiro; Oshimura, Mitsuo; Sato, Koya; Nakada, Naoyuki; Kawamura, Akio; Usui, Takashi; Kamimura, Hidetaka; Tateno, Chise

2015-08-01

We developed murine CYP3A knockout ko chimeric mice with humanized liver expressing human P450S similar to those in humans and whose livers and small intestines do not express murine CYP3A this: approach may overcome effects of residual mouse metabolic enzymes like Cyp3a in conventional chimeric mice with humanized liver, such as PXB-mice [urokinase plasminogen activator/severe combined immunodeficiency (uPA/SCID) mice repopulated with over 70% human hepatocytes] to improve the prediction of drug metabolism and pharmacokinetics in humans. After human hepatocytes were transplanted into Cyp3a KO/uPA/SCID host mice, human albumin levels logarithmically increased until approximately 60 days after transplantation, findings similar to those in PXB-mice. Quantitative real-time-polymerase chain reaction analyses showed that hepatic human P450s, UGTs, SULTs, and transporters mRNA expression levels in Cyp3a KO chimeric mice were also similar to those in PXB-mice and confirmed the absence of Cyp3a11 mRNA expression in mouse liver and intestine. Findings for midazolam and triazolam metabolic activities in liver microsomes were comparable between Cyp3a KO chimeric mice and PXB-mice. In contrast, these activities in the intestine of Cyp3a KO chimeric mice were attenuated compared with PXB-mice. Owing to the knockout of murine Cyp3a, hepatic Cyp2b10 and 2c55 mRNA levels in Cyp3a KO/uPA/SCID mice (without hepatocyte transplants) were 8.4- and 61-fold upregulated compared with PXB-mice, respectively. However, human hepatocyte transplantation successfully restored Cyp2b10 level nearly fully and Cyp2c55 level partly (still 13-fold upregulated) compared with those in PXB-mice. Intestinal Cyp2b10 and 2c55 were also repressed by human hepatocyte transplantation in Cyp3a KO chimeric mice. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Adult Intussusception Caused by Heterotopic Pancreas

Directory of Open Access Journals (Sweden)

Va-Kei Kok

2007-05-01

Full Text Available Heterotopic pancreas causing small bowel intussusception is rare. We report the case of a 24-year-old woman who presented with intermittent episodes of abdominal cramping and pain that had persisted for 10 days. A target-shaped lesion consisting of multiple concentric rings was found on the left side on contrast-enhanced computed tomography. Surgical intervention demonstrated jejunal intussusception caused by a jejunal heterotopic pancreas. Microscopically, several nesidioblastoses of pancreas were identified. Although very rare, small intestinal pancreatic rests may cause subacute bowel obstruction.

Targeted induction of interferon-λ in humanized chimeric mouse liver abrogates hepatotropic virus infection.

Science.gov (United States)

Nakagawa, Shin-ichiro; Hirata, Yuichi; Kameyama, Takeshi; Tokunaga, Yuko; Nishito, Yasumasa; Hirabayashi, Kazuko; Yano, Junichi; Ochiya, Takahiro; Tateno, Chise; Tanaka, Yasuhito; Mizokami, Masashi; Tsukiyama-Kohara, Kyoko; Inoue, Kazuaki; Yoshiba, Makoto; Takaoka, Akinori; Kohara, Michinori

2013-01-01

The interferon (IFN) system plays a critical role in innate antiviral response. We presume that targeted induction of IFN in human liver shows robust antiviral effects on hepatitis C virus (HCV) and hepatitis B virus (HBV). This study used chimeric mice harboring humanized livers and infected with HCV or HBV. This mouse model permitted simultaneous analysis of immune responses by human and mouse hepatocytes in the same liver and exploration of the mechanism of antiviral effect against these viruses. Targeted expression of IFN was induced by treating the animals with a complex comprising a hepatotropic cationic liposome and a synthetic double-stranded RNA analog, pIC (LIC-pIC). Viral replication, IFN gene expression, IFN protein production, and IFN antiviral activity were analyzed (for type I, II and III IFNs) in the livers and sera of these humanized chimeric mice. Following treatment with LIC-pIC, the humanized livers of chimeric mice exhibited increased expression (at the mRNA and protein level) of human IFN-λs, resulting in strong antiviral effect on HBV and HCV. Similar increases were not seen for human IFN-α or IFN-β in these animals. Strong induction of IFN-λs by LIC-pIC occurred only in human hepatocytes, and not in mouse hepatocytes nor in human cell lines derived from other (non-hepatic) tissues. LIC-pIC-induced IFN-λ production was mediated by the immune sensor adaptor molecules mitochondrial antiviral signaling protein (MAVS) and Toll/IL-1R domain-containing adaptor molecule-1 (TICAM-1), suggesting dual recognition of LIC-pIC by both sensor adaptor pathways. These findings demonstrate that the expression and function of various IFNs differ depending on the animal species and tissues under investigation. Chimeric mice harboring humanized livers demonstrate that IFN-λs play an important role in the defense against human hepatic virus infection.

Solitary pancreas retransplant: Study of 22 cases

Directory of Open Access Journals (Sweden)

Tércio Genzini

2006-03-01

Full Text Available Objective: To present our experience with pancreas retransplantin patients previously submitted to simultaneous pancreas-kidneytransplant, pancreas after kidney transplant and pancreastransplant alone. Methods: Between January/1996 and December/2005, 330 pancreas transplants were performed: 308 primarytransplants and 22 (6% retransplants of solitary pancreas. Thefollowing variables were analyzed: patient age; time elapsedbetween the first and the second transplant; causes of loss of thefirst graft; technical characteristics of the transplant andretransplant and the criteria for selecting donors for retransplant.These clinical data were submitted to statistical analysis. Results:The mean age of patients was 34.3 years and the mean elapsedtime between the first and second transplant was 19.3 months.The causes of the first graft loss were venous (8; 35% and arterial(5; 23% thrombosis, chronic rejection (4; 18%, ischemia/reperfusion injury (2, reflux pancreatitis (1, primary non-function(1 and sepsis (1. A second transplant was performed in thesame iliac fossa in 16 patients (72%. Venous drainage wasperformed in the iliac vein in 16 patients (72%, in the inferior venacava in 5 patients (22% and in the portal vein in one patient. 6 allbladder drainage was the technique used in 18 (82% cases andenteric drainage, in 4 patients (18%. Immunosuppressive regimenapplied to all cases was quadruple therapy with antilymphocyteinduction, tacrolimus, mycophenolate mofetil and steroids. Therewas one early death due to sepsis. One-year patient and pancreasgraft survival rates for retransplants were, respectively, 95% and85%. There was no additional risk for removing the pancreas graftat retransplant. Conclusion: Pancreas retransplant was technicallyfeasible in all cases and results similar to those described in theliterature were found for primary pancreas transplant.

Clinical imaging of the pancreas

International Nuclear Information System (INIS)

May, G.; Gardiner, R.

1987-01-01

Featuring more than 300 high-quality radiographs and scan images, clinical imaging of the pancreas systematically reviews all appropriate imaging modalities for diagnosing and evaluating a variety of commonly encountered pancreatic disorders. After presenting a succinct overview of pancreatic embryology, anatomy, and physiology, the authors establish the clinical indications-including postoperative patient evaluation-for radiologic examination of the pancreas. The diagnostic capabilities and limitations of currently available imaging techniques for the pancreas are thoroughly assessed, with carefully selected illustrations depicting the types of images and data obtained using these different techniques. The review of acute and chronic pancreatitis considers the clinical features and possible complications of their variant forms and offers guidance in selecting appropriate imaging studies

CT features of gastric heterotopic pancreas

International Nuclear Information System (INIS)

Wu Guangyao; Tian Zhixiong; Zhang Zaipeng; Huang Xiong

2007-01-01

Objective: To analyze CT findings correlated with pathologic findings in ectopic pancreas of the stomach. Methods: CT scans of 15 surgically proven eases of ectopic pancreas of the stomach were reviewed, and enhanced CT scan was performed in 11 cases. CT findings were correlated with the pathologic findings. Results: All cases had single lesion, and all lesions showed homogeneous density on plain scans without cystic or malignant changes. The size ranged from 1.3 to 3.1 cm, with mean diameter of (1.9±0.2) cm. The lesions were round or oval in shape with broad base against the gastric wall. Two showed central umbilication sign. Only 2 cases were correctly diagnosed prior to operation and the rest were misdiagnosed or diagnosed indistinctly. The locations were in the gastric antrum in 11 cases, in the body in 3, and in fundus in one; The ectopic pancreas located in the greater curvature in 10, and in the lesser curvature in 5. Homogeneous or inhomogeneous strong enhancement similar to the pancreas was seen in 8 cases and they consisted mainly of pancreatic acini with the same histologic features as the pancreas. Three cases showed poor enhancement and consisted mainly of ducts and hypertrophied muscle, pancreatic acini were a minor component. Conclusion: Ectopic pancreas of the stomach showed characteristic locations with the findings of submucosal diseases. Different enhancing patterns were correlated with their pathologic findings. (authors)

A rapid and simple method for cryopreservation of human liver slices

NARCIS (Netherlands)

de Kanter, R; Olinga, Peter; Hof, I.H; de Jager, M.H; Verwillegen, W.A; Slooff, M.JH; Meijer, D.K F; Groothuis, Geny; Koster, H

1. Precision-cut liver slices represent a suitable and convenient in vitro preparation for studying metabolism and toxicity mechanisms of drugs and toxic chemicals. Particularly in the case of human liver slices, cryopreservation would enable more efficient utilization of this scarce and irregularly

Beta-Cell Replacement: Pancreas and Islet Cell Transplantation.

Science.gov (United States)

Niclauss, Nadja; Meier, Raphael; Bédat, Benoît; Berishvili, Ekaterine; Berney, Thierry

2016-01-01

Pancreas and islet transplantation are 2 types of beta-cell replacement therapies for type 1 diabetes mellitus. Since 1966, when pancreas transplantation was first performed, it has evolved to become a highly efficient procedure with high success rates, thanks to advances in surgical technique and immunosuppression. Pancreas transplantation is mostly performed as simultaneous pancreas-kidney transplantation in patients with end-stage nephropathy secondary to diabetes. In spite of its efficiency, pancreas transplantation is still a major surgical procedure burdened by high morbidity, which called for the development of less invasive and hazardous ways of replacing beta-cell function in the past. Islet transplantation was developed in the 1970s as a minimally invasive procedure with initially poor outcomes. However, since the report of the 'Edmonton protocol' in 2000, the functional results of islet transplantation have substantially and constantly improved and are about to match those of whole pancreas transplantation. Islet transplantation is primarily performed alone in nonuremic patients with severe hypoglycemia. Both pancreas transplantation and islet transplantation are able to abolish hypoglycemia and to prevent or slow down the development of secondary complications of diabetes. Pancreas transplantation and islet transplantation should be seen as two complementary, rather than competing, therapeutic approaches for beta-cell replacement that are able to optimize organ donor use and patient care. © 2016 S. Karger AG, Basel.

In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells.

Science.gov (United States)

Ramachandran, Sarada Devi; Schirmer, Katharina; Münst, Bernhard; Heinz, Stefan; Ghafoory, Shahrouz; Wölfl, Stefan; Simon-Keller, Katja; Marx, Alexander; Øie, Cristina Ionica; Ebert, Matthias P; Walles, Heike; Braspenning, Joris; Breitkopf-Heinlein, Katja

2015-01-01

In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process). Proliferating upcyte® cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte® cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.

Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro.

Science.gov (United States)

Maschmeyer, Ilka; Hasenberg, Tobias; Jaenicke, Annika; Lindner, Marcus; Lorenz, Alexandra Katharina; Zech, Julie; Garbe, Leif-Alexander; Sonntag, Frank; Hayden, Patrick; Ayehunie, Seyoum; Lauster, Roland; Marx, Uwe; Materne, Eva-Maria

2015-09-01

Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called "human-on-a-chip" concepts are aiming to replace respective animals and humans in substance evaluation with miniaturized functional human organisms. The major technical hurdle toward success in this field is the life-like combination of human barrier organ models, such as intestine, lung or skin, with parenchymal organ equivalents, such as liver, at the smallest biologically acceptable scale. Here, we report on a reproducible homeostatic long-term co-culture of human liver equivalents with either a reconstructed human intestinal barrier model or a human skin biopsy applying a microphysiological system. We used a multi-organ chip (MOC) platform, which provides pulsatile fluid flow within physiological ranges at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact intestinal barrier model and an air-liquid interface for the skin model during their co-culture with the liver equivalents respectively at (1)/100.000 the scale of their human counterparts in vivo. To increase the degree of organismal emulation, microfluidic channels of the liver-skin co-culture could be successfully covered with human endothelial cells, thus mimicking human vasculature, for the first time. Finally, exposure routes emulating oral and systemic administration in humans have been qualified by applying a repeated dose administration of a model substance - troglitazone - to the chip-based co-cultures. Copyright © 2015. Published by Elsevier B.V.

In Vivo Senescence in the Sbds-Deficient Murine Pancreas: Cell-Type Specific Consequences of Translation Insufficiency.

Directory of Open Access Journals (Sweden)

Marina E Tourlakis

2015-06-01

Full Text Available Genetic models of ribosome dysfunction show selective organ failure, highlighting a gap in our understanding of cell-type specific responses to translation insufficiency. Translation defects underlie a growing list of inherited and acquired cancer-predisposition syndromes referred to as ribosomopathies. We sought to identify molecular mechanisms underlying organ failure in a recessive ribosomopathy, with particular emphasis on the pancreas, an organ with a high and reiterative requirement for protein synthesis. Biallelic loss of function mutations in SBDS are associated with the ribosomopathy Shwachman-Diamond syndrome, which is typified by pancreatic dysfunction, bone marrow failure, skeletal abnormalities and neurological phenotypes. Targeted disruption of Sbds in the murine pancreas resulted in p53 stabilization early in the postnatal period, specifically in acinar cells. Decreased Myc expression was observed and atrophy of the adult SDS pancreas could be explained by the senescence of acinar cells, characterized by induction of Tgfβ, p15(Ink4b and components of the senescence-associated secretory program. This is the first report of senescence, a tumour suppression mechanism, in association with SDS or in response to a ribosomopathy. Genetic ablation of p53 largely resolved digestive enzyme synthesis and acinar compartment hypoplasia, but resulted in decreased cell size, a hallmark of decreased translation capacity. Moreover, p53 ablation resulted in expression of acinar dedifferentiation markers and extensive apoptosis. Our findings indicate a protective role for p53 and senescence in response to Sbds ablation in the pancreas. In contrast to the pancreas, the Tgfβ molecular signature was not detected in fetal bone marrow, liver or brain of mouse models with constitutive Sbds ablation. Nevertheless, as observed with the adult pancreas phenotype, disease phenotypes of embryonic tissues, including marked neuronal cell death due to apoptosis

In Vivo Senescence in the Sbds-Deficient Murine Pancreas: Cell-Type Specific Consequences of Translation Insufficiency

Science.gov (United States)

Tourlakis, Marina E.; Zhang, Siyi; Ball, Heather L.; Gandhi, Rikesh; Liu, Hongrui; Zhong, Jian; Yuan, Julie S.; Guidos, Cynthia J.; Durie, Peter R.; Rommens, Johanna M.

2015-01-01

Genetic models of ribosome dysfunction show selective organ failure, highlighting a gap in our understanding of cell-type specific responses to translation insufficiency. Translation defects underlie a growing list of inherited and acquired cancer-predisposition syndromes referred to as ribosomopathies. We sought to identify molecular mechanisms underlying organ failure in a recessive ribosomopathy, with particular emphasis on the pancreas, an organ with a high and reiterative requirement for protein synthesis. Biallelic loss of function mutations in SBDS are associated with the ribosomopathy Shwachman-Diamond syndrome, which is typified by pancreatic dysfunction, bone marrow failure, skeletal abnormalities and neurological phenotypes. Targeted disruption of Sbds in the murine pancreas resulted in p53 stabilization early in the postnatal period, specifically in acinar cells. Decreased Myc expression was observed and atrophy of the adult SDS pancreas could be explained by the senescence of acinar cells, characterized by induction of Tgfβ, p15Ink4b and components of the senescence-associated secretory program. This is the first report of senescence, a tumour suppression mechanism, in association with SDS or in response to a ribosomopathy. Genetic ablation of p53 largely resolved digestive enzyme synthesis and acinar compartment hypoplasia, but resulted in decreased cell size, a hallmark of decreased translation capacity. Moreover, p53 ablation resulted in expression of acinar dedifferentiation markers and extensive apoptosis. Our findings indicate a protective role for p53 and senescence in response to Sbds ablation in the pancreas. In contrast to the pancreas, the Tgfβ molecular signature was not detected in fetal bone marrow, liver or brain of mouse models with constitutive Sbds ablation. Nevertheless, as observed with the adult pancreas phenotype, disease phenotypes of embryonic tissues, including marked neuronal cell death due to apoptosis, were determined to

De novo malignancy after pancreas transplantation in Japan.

Science.gov (United States)

Tomimaru, Y; Ito, T; Marubashi, S; Kawamoto, K; Tomokuni, A; Asaoka, T; Wada, H; Eguchi, H; Mori, M; Doki, Y; Nagano, H

2015-04-01

Long-term immunosuppression is associated with an increased risk of cancer. Especially, the immunosuppression in pancreas transplantation is more intensive than that in other organ transplantation because of its strong immunogenicity. Therefore, it suggests that the risk of post-transplant de novo malignancy might increase in pancreas transplantation. However, there have been few studies of de novo malignancy after pancreas transplantation. The aim of this study was to analyze the incidence of de novo malignancy after pancreas transplantation in Japan. Post-transplant patients with de novo malignancy were surveyed and characterized in Japan. Among 107 cases receiving pancreas transplantation in Japan between 2001 and 2010, de novo malignancy developed in 9 cases (8.4%): post-transplant lymphoproliferative disorders in 6 cases, colon cancer in 1 case, renal cancer in 1 case, and brain tumor in 1 case. We clarified the incidence of de novo malignancy after pancreas transplantation in Japan. Copyright © 2015 Elsevier Inc. All rights reserved.

Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

Science.gov (United States)

2014-01-01

Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION: EARLY POSTOPERATIVE COMPLICATIONS

Directory of Open Access Journals (Sweden)

M.Sh. Khubutia

2014-01-01

Full Text Available Aim: evaluation of the incidence of early postoperative complications after simultaneous pancreas-kidney transplantation.Materials and methods. The analysis of early postoperative complications after simultaneous pancreas-kidney transplantation is presented in the paper, the most rational diagnostic algorithms, non-surgical and surgical complications’ treatment; the outcomes of the SPKT are reported.Results. 15,6% of patients experienced surgical complications, 12,5% – immunological complications, 12,5% – infectious complications, 6,25% – complications of the immunosuppressive therapy. 1-year patient survival after SPKT was 91,4%; pancreas graft survival – 85,7%; kidney graft survival – 88,6%.Conclusion. The incidence of early postoperative complications after simultaneous pancreas-kidney transplantation remains signifi cant in spite of progressive improvement of simultaneous pancreas-kidney transplantation due to surgical technique improvement, introduction of new antibacterial and immunosuppressive agents. Data, we recovered, fully correspond to the data obtained from the global medical community.

Annular pancreas in adult: a case report

International Nuclear Information System (INIS)

Moreira Neto, M.

1992-01-01

A case of a patient complaining of recurrent symptomatology of the upper abdomen and sub occlusion of the gastrointestinal tract with stenosis of the second portion of duodenum and mass evolving the head of pancreas at echographic study, confirmed by CT is presented. Contrasted oral studies confirmed that the mass evolved the stenotic segment, suggesting annular pancreas. Surgery confirmed the presence of annular pancreas surrounding the second portion of duodenum. (author)

Diabetic Foot Complications Despite Successful Pancreas Transplantation.

Science.gov (United States)

Seo, Dong-Kyo; Lee, Ho Seong; Park, Jungu; Ryu, Chang Hyun; Han, Duck Jong; Seo, Sang Gyo

2017-06-01

It is known that successful pancreas transplantation enables patients with diabetes to maintain a normal glucose level without insulin and reduces diabetes-related complications. However, we have little information about the foot-specific morbidity in patients who have undergone successful pancreas transplantation. The purpose of this study was to investigate the prevalence and predisposing factors for foot complications after successful pancreas transplantation. This retrospective study included 218 patients (91 males, 127 females) who had undergone pancreas transplantation for diabetes. The mean age was 40.7 (range, 15-76) years. Diabetes type, transplantation type, body mass index, and diabetes duration before transplantation were confirmed. After pancreas transplantation, the occurrence and duration of foot and ankle complications were assessed. Twenty-two patients (10.1%) had diabetic foot complications. Fifteen patients (6.9%) had diabetic foot ulcer and 7 patients (3.2%) had Charcot arthropathy. Three patients had both diabetic foot ulcer and Charcot arthropathy. Three insufficiency fractures (1.4%) were included. Mean time of complications after transplantation was 18.5 (range, 2-77) months. Creatinine level 1 year after surgery was higher in the complication group rather than the noncomplication group ( P = .02). Complications of the foot and ankle still occurred following pancreas transplantation in patients with diabetes. Level III, comparative study.

Carcinoma of the pancreas head in a woman, surviving 13 years after radiotherapy of a blastoma lymphoreticularis of the stomach

Energy Technology Data Exchange (ETDEWEB)

Kharbov, I; Velichkov, L; Angelova, V; Velev, G [Meditsinska Akademiya, Sofia (Bulgaria). Katedra po Rentgenologiya i Radiologiya

1974-01-01

Combination of two neoplastic processes with different morphological characteristics in patients is rarely observed. A case of blastoma lymphoreticularis with abdominal localization, liver, spleen, abdominal lymph nodes and predominantly the stomach, is reported. The diagnosis is verified by histological examination after laparotomia. Radiotherapy (telecobalto therapy and deep roentgen therapy) is carried out from 1960 to 1968. At dissection (1972) a total destruction of the blastoma and the development of a carcinoma of the pancreas head are found. As a result from the radiotherapy a summary dose of 1750 rads for 8 years in the pancreas area is realized. This is of the range of the optimal blastomogenic dose, which, together with the time of the carcinoma development, support the supposition for the radioinduction of the carcinoma. (INIS)

A Study on Pancreas Scanning with Selenium{sup 75}-Selenomethionine

Energy Technology Data Exchange (ETDEWEB)

Shin, Hyun Chan; Toh, Sang Hee; Ra, Woo Youn; Suh, Chul Sung [Presbyterian Hospital, Deagu (Korea, Republic of)

1968-03-15

Radiographic visualization of the pancreas is a difficult problem, but the direct visualization of the pancreas is possible by the injection of the amino-acid methionine tagged with selenium{sup 75} (Se{sup 75}). In order to know the diagnostic value of pancreas scanning, scans were performed on 23 cases using selenium{sup 75}-Selenomethionine. These cases were also given egg white, probanthine and morphine. 1) Good visualization of the pancreas scanning was observed on 19 cases, presumably with normal pancreas. 2) A case which showed diffusely decreased uptake on pancreas scanning was proven to have lesions in the bile duct and the gall bladder. 3) Of those two cases which showed localized cold area, one had pancreas cyst and the other one was not explored. 4) A case which showed no visualization of the pancreas was proven to have pancreatic carcinoma. 5) Two cases which showed widened duodenal loop by upper gastro-intestinal series revealed normal pancreas scanning, and no pancreatic disease was found in both cases.

Estimation of ellagic acid and/or repaglinide effects on insulin signaling, oxidative stress, and inflammatory mediators of liver, pancreas, adipose tissue, and brain in insulin resistant/type 2 diabetic rats.

Science.gov (United States)

Amin, Mohamed M; Arbid, Mahmoud S

2017-02-01

Even though ellagic acid has previously been valued in many models of cancer, so far its full mechanistic effect as a natural antiapoptotic agent in the prevention of type 2 diabetes complications has not been completely elucidated, which was the goal of this study. We fed albino rats a high-fat fructose diet (HFFD) for 2 months to induce insulin resistance/type 2 diabetes and then treated the rats with ellagic acid (10 mg/kg body weight, orally) and/or repaglinide (0.5 mg/kg body weight, orally) for 2 weeks. At the serum level, ellagic acid challenged the consequences of HFFD, significantly improving the glucose/insulin balance, liver enzymes, lipid profile, inflammatory cytokines, redox level, adipokines, ammonia, and manganese. At the tissue level (liver, pancreas, adipose tissue, and brain), ellagic acid significantly enhanced insulin signaling, autophosphorylation, adiponectin receptors, glucose transporters, inflammatory mediators, and apoptotic markers. Remarkably, combined treatment with both ellagic acid and repaglinide had a more pronounced effect than treatment with either alone. These outcomes give new insight into the promising molecular mechanisms by which ellagic acid modulates numerous factors induced in the progression of diabetes.

Radiologic findings of annular pancreas divisum : a case report

International Nuclear Information System (INIS)

Choi, Dong Sik; Lee, Dong Ho; Ko, Young Tae; Han, Tae Il; Yoon, Youp; Dong, Suk Ho

1996-01-01

Annular pancreas divisum is a very rare congenital anomaly involving the coexistence of an annular pancreas and pancreatic divisum in one pancreas, and showing characteristic radiologic findings of ring-like pancreatic tissue surrounding the second portion of the duodenum and no evidence of connection between ventral and dorsal ductal systems. We described the radiologic findings of annular pancreas divisum, diagnosed by hypotonic duodenography, CT and ERCP

Current topics in glycemic control by wearable artificial pancreas or bedside artificial pancreas with closed-loop system.

Science.gov (United States)

Hanazaki, Kazuhiro; Munekage, Masaya; Kitagawa, Hiroyuki; Yatabe, Tomoaki; Munekage, Eri; Shiga, Mai; Maeda, Hiromichi; Namikawa, Tsutomu

2016-09-01

The incidence of diabetes is increasing at an unprecedented pace and has become a serious health concern worldwide during the last two decades. Despite this, adequate glycemic control using an artificial pancreas has not been established, although the 21st century has seen rapid developments in this area. Herein, we review current topics in glycemic control for both the wearable artificial pancreas for type 1 and type 2 diabetic patients and the bedside artificial pancreas for surgical diabetic patients. In type 1 diabetic patients, nocturnal hypoglycemia associated with insulin therapy remains a serious problem that could be addressed by the recent development of a wearable artificial pancreas. This smart phone-like device, comprising a real-time, continuous glucose monitoring system and insulin pump system, could potentially significantly reduce nocturnal hypoglycemia compared with conventional glycemic control. Of particular interest in this space are the recent inventions of a low-glucose suspend feature in the portable systems that automatically stops insulin delivery 2 h following a glucose sensor value <70 mg/dL and a bio-hormonal pump system consisting of insulin and glucagon pumps. Perioperative tight glycemic control using a bedside artificial pancreas with the closed-loop system has also proved safe and effective for not only avoiding hypoglycemia, but also for reducing blood glucose level variability resulting in good surgical outcomes. We hope that a more sophisticated artificial pancreas with closed-loop system will now be taken up for routine use worldwide, providing enormous relief for patients suffering from uncontrolled hyperglycemia, hypoglycemia, and/or variability in blood glucose concentrations.

Amylin under examination. Fibrillogenic polypeptide hormone of the pancreas

Directory of Open Access Journals (Sweden)

Małgorzata Marszałek

2014-01-01

Full Text Available In patients or animals affected by type 2 diabetes mellitus (DM2, non-insulin dependent diabetes mellitus [NIDDM] some pathological deposits, called amyloid, are observed among cells of islets of Langerhans. Among other constituents, deposits consist of an insoluble, fibrillar form of peptide neurohormone called amylin, produced by pancreatic beta cells. It is thought that formation of fibrillar deposits of misfolded and aggregated peptide is highly toxic to beta cells and leads to cell dysfunction, cell loss, pancreas destruction and progress of the disease. This relatively small 37-amino acid peptide constitutes a serious scientific, research and to some extent a medical problem. This article presents amylin as a hormone, neurohormone and as a fibrillating molecule which participates in amyloid deposit formation in human and animal pancreas. The role of some amino acids important for fibril formation has been highlighted.

Targeted induction of interferon-λ in humanized chimeric mouse liver abrogates hepatotropic virus infection.

Directory of Open Access Journals (Sweden)

Shin-ichiro Nakagawa

Full Text Available BACKGROUND & AIMS: The interferon (IFN system plays a critical role in innate antiviral response. We presume that targeted induction of IFN in human liver shows robust antiviral effects on hepatitis C virus (HCV and hepatitis B virus (HBV. METHODS: This study used chimeric mice harboring humanized livers and infected with HCV or HBV. This mouse model permitted simultaneous analysis of immune responses by human and mouse hepatocytes in the same liver and exploration of the mechanism of antiviral effect against these viruses. Targeted expression of IFN was induced by treating the animals with a complex comprising a hepatotropic cationic liposome and a synthetic double-stranded RNA analog, pIC (LIC-pIC. Viral replication, IFN gene expression, IFN protein production, and IFN antiviral activity were analyzed (for type I, II and III IFNs in the livers and sera of these humanized chimeric mice. RESULTS: Following treatment with LIC-pIC, the humanized livers of chimeric mice exhibited increased expression (at the mRNA and protein level of human IFN-λs, resulting in strong antiviral effect on HBV and HCV. Similar increases were not seen for human IFN-α or IFN-β in these animals. Strong induction of IFN-λs by LIC-pIC occurred only in human hepatocytes, and not in mouse hepatocytes nor in human cell lines derived from other (non-hepatic tissues. LIC-pIC-induced IFN-λ production was mediated by the immune sensor adaptor molecules mitochondrial antiviral signaling protein (MAVS and Toll/IL-1R domain-containing adaptor molecule-1 (TICAM-1, suggesting dual recognition of LIC-pIC by both sensor adaptor pathways. CONCLUSIONS: These findings demonstrate that the expression and function of various IFNs differ depending on the animal species and tissues under investigation. Chimeric mice harboring humanized livers demonstrate that IFN-λs play an important role in the defense against human hepatic virus infection.

Computed tomographic evaluation of the pancreas

International Nuclear Information System (INIS)

Stanley, R.J.; Sagel, S.S.

1979-01-01

Analysis of the clinical experience in the evaluation of the pancreas with computed tomography (CT) since October 1975 indicates that it is a reliable, often specific and relatively noninvasive method for the detection of pancreatic neoplasms and the varied manifestations of pancreatitis and its complications. The normal pancreas is clearly imaged in all but the leanest or uncooperative patients. Tumors of pancreas are identified as focal alteration in the size or contour of the gland. Obliteration of contiguous fat planes, areas of necrosis within the tumor, and secondary effects on the uninvolved parts of the pancreas and biliary tree can be identified. CBT has substantially reduced the need for pancreatic angiography, percutaneous transhepatic cholangiography, and endoscopic retrograde pancreatocholangiography at this medical center. Although a definitive comparison of ultrasound and CT has not yet been accomplished, initial experience indicates that a complementary rather than competitive relationship will develop between the two imaging methods. (orig.) 891 MG/orig. 892 MB [de

FoxO1 gain of function in the pancreas causes glucose intolerance, polycystic pancreas, and islet hypervascularization.

Directory of Open Access Journals (Sweden)

Osamu Kikuchi

Full Text Available Genetic studies revealed that the ablation of insulin/IGF-1 signaling in the pancreas causes diabetes. FoxO1 is a downstream transcription factor of insulin/IGF-1 signaling. We previously reported that FoxO1 haploinsufficiency restored β cell mass and rescued diabetes in IRS2 knockout mice. However, it is still unclear whether FoxO1 dysregulation in the pancreas could be the cause of diabetes. To test this hypothesis, we generated transgenic mice overexpressing constitutively active FoxO1 specifically in the pancreas (TG. TG mice had impaired glucose tolerance and some of them indeed developed diabetes due to the reduction of β cell mass, which is associated with decreased Pdx1 and MafA in β cells. We also observed increased proliferation of pancreatic duct epithelial cells in TG mice and some mice developed a polycystic pancreas as they aged. Furthermore, TG mice exhibited islet hypervascularities due to increased VEGF-A expression in β cells. We found FoxO1 binds to the VEGF-A promoter and regulates VEGF-A transcription in β cells. We propose that dysregulation of FoxO1 activity in the pancreas could account for the development of diabetes and pancreatic cysts.

SU-E-J-65: Motion Difference Between the Pancreas and Nearby Veins for Pancreas Motion Monitoring Using Ultrasound During Radiation Therapy

International Nuclear Information System (INIS)

Omari, E; Erickson, B; Li, X; Zhang, J

2015-01-01

Purpose: As it is generally difficult to outline the pancreas on an ultrasound b-mode image, visualized structures such as the portal or the splenic veins are assumed to have the same motion as the pancreas. These structures can be used as a surrogate for monitoring pancreas motion during radiation therapy (RT) delivery using ultrasound. To verify this assumption, we studied the motion difference between the head of the pancreas, the portal vein, the tail of the pancreas, and splenic vein. Methods: 4DCT data acquired during RT simulation were analyzed for a total of 5 randomly selected patients with pancreatic cancer. The data was sorted into 10 respiratory phases from 0% to 90% (0%: end of the inspiration, 50%: end of expiration) . The head of the pancreas (HP), tail of the pancreas (TP), portal vein (PV), and splenic vein (SV) were contoured on all 10 phases. The volume change and motion were measured in the left-right (LR), anterior-superior (AP), and superior-inferior (SI) directions. Results: The volume change for all patients/phases were: 1.2 ± 3% for HP, 0.78 ± 1.6% for PV, 2.5 ± 2.9% for TP, and 0.53 ± 2.1% for SV. Motion for each structure was estimated from the centroid displacements due to the uniformity of the structures and the small volume change. The measured motion between HP and PV was: LR: 0.1 ± 0.17 mm, AP: 0.04 ± 0.1 mm, SI: 0.17 ± 0.16 mm and between TP and the PV was: LR: 0.05 ± 0.3 mm, AP: 0.1 ± 0.4 mm, SI: 0.01 ± 0.022 mm. Conclusion: There are small motion differences between the portal vein and the head of the pancreas, and the splenic vein and the tail of the pancreas. This suggests the feasibility of utilizing these features for monitoring the pancreas motion during radiation therapy

Ultrasound elastographic techniques in focal liver lesions.

Science.gov (United States)

Conti, Clara Benedetta; Cavalcoli, Federica; Fraquelli, Mirella; Conte, Dario; Massironi, Sara

2016-03-07

Elastographic techniques are new ultrasound-based imaging techniques developed to estimate tissue deformability/stiffness. Several ultrasound elastographic approaches have been developed, such as static elastography, transient elastography and acoustic radiation force imaging methods, which include point shear wave and shear wave imaging elastography. The application of these methods in clinical practice aims at estimating the mechanical tissues properties. One of the main settings for the application of these tools has been liver stiffness assessment in chronic liver disease, which has been studied mainly using transient elastography. Another field of application for these techniques is the assessment of focal lesions, detected by ultrasound in organs such as pancreas, prostate, breast, thyroid, lymph nodes. Considering the frequency and importance of the detection of focal liver lesions through routine ultrasound, some studies have also aimed to assess the role that elestography can play in studying the stiffness of different types of liver lesions, in order to predict their nature and thus offer valuable non-invasive methods for the diagnosis of liver masses.

Progress and challenges of the bioartificial pancreas

Science.gov (United States)

Hwang, Patrick T. J.; Shah, Dishant K.; Garcia, Jacob A.; Bae, Chae Yun; Lim, Dong-Jin; Huiszoon, Ryan C.; Alexander, Grant C.; Jun, Ho-Wook

2016-11-01

Pancreatic islet transplantation has been validated as a treatment for type 1 diabetes since it maintains consistent and sustained type 1 diabetes reversal. However, one of the major challenges in pancreatic islet transplantation is the body's natural immune response to the implanted islets. Immunosuppressive drug treatment is the most popular immunomodulatory approach for islet graft survival. However, administration of immunosuppressive drugs gives rise to negative side effects, and long-term effects are not clearly understood. A bioartificial pancreas is a therapeutic approach to enable pancreatic islet transplantation without or with minimal immune suppression. The bioartificial pancreas encapsulates the pancreatic islets in a semi-permeable environment which protects islets from the body's immune responses, while allowing the permeation of insulin, oxygen, nutrients, and waste. Many groups have developed various types of the bioartificial pancreas and tested their efficacy in animal models. However, the clinical application of the bioartificial pancreas still requires further investigation. In this review, we discuss several types of bioartificial pancreases and address their advantages and limitations. We also discuss recent advances in bioartificial pancreas applications with microfluidic or micropatterning technology.

Human Precision-Cut Liver Slices as an ex Vivo Model to Study Idiosyncratic Drug-Induced Liver Injury

NARCIS (Netherlands)

Hadi, Mackenzie; Westra, Inge M.; Starokozhko, Viktoriia; Dragovic, Sanja; Merema, M.T.; Groothuis, Geny M. M.

Idiosyncratic drug-induced liver injury (IDILI) is a major problem during drug development and has caused drug withdrawal and black-box warnings. Because of the low concordance of the hepatotoxicity of drugs in animals and humans, robust screening methods using human tissue are needed to predict

Radiosensitivity Differences Between Liver Metastases Based on Primary Histology Suggest Implications for Clinical Outcomes After Stereotactic Body Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Ahmed, Kamran A.; Caudell, Jimmy J. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); El-Haddad, Ghassan [Department of Interventional Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Berglund, Anders E.; Welsh, Eric A. [Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Yue, Binglin [Department of Biostastistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Hoffe, Sarah E.; Naghavi, Arash O.; Abuodeh, Yazan A.; Frakes, Jessica M. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Eschrich, Steven A. [Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Torres-Roca, Javier F., E-mail: Javier.torresroca@moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States)

2016-08-01

Purpose/Objectives: Evidence from the management of oligometastases with stereotactic body radiation therapy (SBRT) reveals differences in outcomes based on primary histology. We have previously identified a multigene expression index for tumor radiosensitivity (RSI) with validation in multiple independent cohorts. In this study, we assessed RSI in liver metastases and assessed our clinical outcomes after SBRT based on primary histology. Methods and Materials: Patients were identified from our prospective, observational protocol. The previously tested RSI 10 gene assay was run on samples and calculated using the published algorithm. An independent cohort of 33 patients with 38 liver metastases treated with SBRT was used for clinical correlation. Results: A total of 372 unique metastatic liver lesions were identified for inclusion from our prospective, institutional metadata pool. The most common primary histologies for liver metastases were colorectal adenocarcinoma (n=314, 84.4%), breast adenocarcinoma (n=12, 3.2%), and pancreas neuroendocrine (n=11, 3%). There were significant differences in RSI of liver metastases based on histology. The median RSIs for liver metastases in descending order of radioresistance were gastrointestinal stromal tumor (0.57), melanoma (0.53), colorectal neuroendocrine (0.46), pancreas neuroendocrine (0.44), colorectal adenocarcinoma (0.43), breast adenocarcinoma (0.35), lung adenocarcinoma (0.31), pancreas adenocarcinoma (0.27), anal squamous cell cancer (0.22), and small intestine neuroendocrine (0.21) (P<.0001). The 12-month and 24-month Kaplan-Meier rates of local control (LC) for colorectal lesions from the independent clinical cohort were 79% and 59%, compared with 100% for noncolorectal lesions (P=.019), respectively. Conclusions: In this analysis, we found significant differences based on primary histology. This study suggests that primary histology may be an important factor to consider in SBRT radiation dose selection.

Radiosensitivity Differences Between Liver Metastases Based on Primary Histology Suggest Implications for Clinical Outcomes After Stereotactic Body Radiation Therapy

International Nuclear Information System (INIS)

Ahmed, Kamran A.; Caudell, Jimmy J.; El-Haddad, Ghassan; Berglund, Anders E.; Welsh, Eric A.; Yue, Binglin; Hoffe, Sarah E.; Naghavi, Arash O.; Abuodeh, Yazan A.; Frakes, Jessica M.; Eschrich, Steven A.; Torres-Roca, Javier F.

2016-01-01

Purpose/Objectives: Evidence from the management of oligometastases with stereotactic body radiation therapy (SBRT) reveals differences in outcomes based on primary histology. We have previously identified a multigene expression index for tumor radiosensitivity (RSI) with validation in multiple independent cohorts. In this study, we assessed RSI in liver metastases and assessed our clinical outcomes after SBRT based on primary histology. Methods and Materials: Patients were identified from our prospective, observational protocol. The previously tested RSI 10 gene assay was run on samples and calculated using the published algorithm. An independent cohort of 33 patients with 38 liver metastases treated with SBRT was used for clinical correlation. Results: A total of 372 unique metastatic liver lesions were identified for inclusion from our prospective, institutional metadata pool. The most common primary histologies for liver metastases were colorectal adenocarcinoma (n=314, 84.4%), breast adenocarcinoma (n=12, 3.2%), and pancreas neuroendocrine (n=11, 3%). There were significant differences in RSI of liver metastases based on histology. The median RSIs for liver metastases in descending order of radioresistance were gastrointestinal stromal tumor (0.57), melanoma (0.53), colorectal neuroendocrine (0.46), pancreas neuroendocrine (0.44), colorectal adenocarcinoma (0.43), breast adenocarcinoma (0.35), lung adenocarcinoma (0.31), pancreas adenocarcinoma (0.27), anal squamous cell cancer (0.22), and small intestine neuroendocrine (0.21) (P<.0001). The 12-month and 24-month Kaplan-Meier rates of local control (LC) for colorectal lesions from the independent clinical cohort were 79% and 59%, compared with 100% for noncolorectal lesions (P=.019), respectively. Conclusions: In this analysis, we found significant differences based on primary histology. This study suggests that primary histology may be an important factor to consider in SBRT radiation dose selection.

Measure of pancreas transection and postoperative pancreatic fistula.

Science.gov (United States)

Takahashi, Shinichiro; Gotohda, Naoto; Kato, Yuichiro; Konishi, Masaru

2016-05-15

In pancreaticoduodenectomy (PD), a standard protocol for pancreas transection has not been established although the method of pancreas transection might be involved in the occurrence of postoperative pancreatic fistula (POPF). This study aimed to compare whether pancreas transection by ultrasonically activated shears (UAS) or that by scalpel contributed more to POPF development. A prospective database of 171 patients who underwent PD for periampullary tumor at National Cancer Center Hospital East between January 2010 and June 2013 was reviewed. Among the 171 patients, 93 patients with soft pancreas were specifically included in this study. Surgical results and background were compared between patients with pancreas transection by UAS and scalpel to evaluate the effectiveness of UAS on reducing POPF. Body mass index, main pancreatic duct diameter, or other clinicopathologic factors that have been reported as predictive factors for POPF were not significantly different between the two groups. The incidence of all grades of POPF and that of grade B were significantly lower in the scalpel group (52%, 4%) than in the UAS group (74%, 42%). Postoperative complications ≥ grade III were also significantly fewer in the scalpel group. Scalpel transection was less associated with POPF than UAS transection in patients who underwent PD for soft pancreas. The method of pancreas transection plays an important role in the prevention of clinical POPF. Copyright © 2016 Elsevier Inc. All rights reserved.

Pancreas Scanning with Se{sup 75}-Selenomethionine; Scintigraphie du Pancreas avec de la Selenomethionine Marquee au Selenium-75; Skennirovanie podzheludochnoj zhelezy s pomoshch'yu selenometionina, mechennogo Selenom-75; Exploracion del Pancreas con Selenometionina-{sup 75}Se

Energy Technology Data Exchange (ETDEWEB)

Blau, M. [Department of Nuclear Medicine, Roswell Park Memorial Institute, Buffalo, NY (United States)

1964-10-15

Amino-acids show a high degree of localization in the pancreas during the first few hours after administration. This specificity is related to the rapid synthesis and turnover of the digestive enzymes. Since none of the elements in the structure of amino-acids (C,H, N,0 and S) have suitable gamma-emitting isotopes, they cannot be used for scanning. Several I{sup 131} derivatives of amino-acids were prepared and tested, but the pancreas-localizing property of the original amino-acid was lost in every case. The chemical similarity of selenium and sulphur suggested that the selenium analogue of methionine might resemble methionine closely enough to take its place in protein synthesis. Se{sup 75} (halflife, 128 d; principal gamma-ray, 0.27 MeV) is suitable for scanning. Selenium-75-selenomethionine was prepared by yeast biosynthesis. The yeast was grown on a low sulphur medium containing high specific activity Se{sup 75} as selenite. After extraction with ether and hot trichloracetic acid, the protein residue was hydrolysed with hydrochloric acid The resulting amino-acid mixture was separated by column chromatography. Selenium-75-selenomethionine prepared in this manner showed biological properties of a natural aminoacid. The uptake in pancreas was about 7% of the administered dose and the concentration in a gramme of pancreas was seven times that in a gramme of liver. Blood and other organs had even lower uptakes. The clinical usefulness of pancreas scanning is now being evaluated. Tumours of the pancreas have been found as areas of decreased uptake. There is no concentration of selenomethionine in cases of acute pancreatitis. It is too early to give a statistical estimate of our ability to find tumours of the pancreas by this technique. The estimated total body dose from this procedure is less than 1 rad. The selenium dose is only a. few microgrammes and represents no toxicity hazard. (author) [Spanish] Los aminoacidos tienden a localizarse en el pancreas durante las

Human precision-cut liver slices as an ex vivo model to study idiosyncratic drug-induced liver injury

NARCIS (Netherlands)

Hadi, Mackenzie; Westra, Inge; Starokozhko, Viktoriia; Dragovic, Sanja; Merema, Maja; Groothuis, Genoveva

2013-01-01

Idiosyncratic drug-induced liver injury (IDILI) is a major problem during drug development and has caused drug withdrawal and black-box warnings. Due to the low concordance of the hepatotoxicity of drugs in animals and humans, robust screening methods using human tissue are needed to predict and to

Pancreas transplantation: an overview

Directory of Open Access Journals (Sweden)

Andre Ibrahim David

2010-12-01

Full Text Available Pancreas transplantation is the only treatment able to reestablish normal glucose and glycated hemoglobin levels in insulin-dependent diabetic patients without the use of exogenous insulin. The evolution of pancreas transplantation in treatment of diabetes was determined by advances in the fields of surgical technique, organ preservation and immunosuppressants. The main complication leading to graft loss is technical failure followed by acute or chronic rejection. Technical failure means graft loss within the first three months following transplantation due to vascular thrombosis (50%, pancreatitis (20%, infection (18%, fistula (6.5% and bleeding (2.4%. Immunological complications still affect 30% of patients, and rejection is the cause of graft loss in 10% of cases. Chronic rejection is the most common late complication. Cardiovascular diseases are the most common causes of late mortality in pancreas transplantation, so it remains the most effective treatment for type 1 diabetes patients. There is a significant improvement in quality of life and in patient’s survival rates. The development of islet transplantation could eliminate or minimize surgical complications and immunosuppression.

HIV-Antiretroviral Therapy Induced Liver, Gastrointestinal, and Pancreatic Injury

Directory of Open Access Journals (Sweden)

Manuela G. Neuman

2012-01-01

Full Text Available The present paper describes possible connections between antiretroviral therapies (ARTs used to treat human immunodeficiency virus (HIV infection and adverse drug reactions (ADRs encountered predominantly in the liver, including hypersensitivity syndrome reactions, as well as throughout the gastrointestinal system, including the pancreas. Highly active antiretroviral therapy (HAART has a positive influence on the quality of life and longevity in HIV patients, substantially reducing morbidity and mortality in this population. However, HAART produces a spectrum of ADRs. Alcohol consumption can interact with HAART as well as other pharmaceutical agents used for the prevention of opportunistic infections such as pneumonia and tuberculosis. Other coinfections that occur in HIV, such as hepatitis viruses B or C, cytomegalovirus, or herpes simplex virus, further complicate the etiology of HAART-induced ADRs. The aspect of liver pathology including liver structure and function has received little attention and deserves further evaluation. The materials used provide a data-supported approach. They are based on systematic review and analysis of recently published world literature (MedLine search and the experience of the authors in the specified topic. We conclude that therapeutic and drug monitoring of ART, using laboratory identification of phenotypic susceptibilities, drug interactions with other medications, drug interactions with herbal medicines, and alcohol intake might enable a safer use of this medication.

Metastatic Renal Cell Carcinoma to the Pancreas: A Review.

Science.gov (United States)

Cheng, Shaun Kian Hong; Chuah, Khoon Leong

2016-06-01

The pancreas is an unusual site for tumor metastasis, accounting for only 2% to 5% of all malignancies affecting the pancreas. The more common metastases affecting the pancreas include renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas, and sarcomas. Although pancreatic involvement by nonrenal malignancies indicates widespread systemic disease, metastatic renal cell carcinoma to the pancreas often represents an isolated event and is thus amenable to surgical resection, which is associated with long-term survival. As such, it is important to accurately diagnose pancreatic involvement by metastatic renal cell carcinoma on histology, especially given that renal cell carcinoma metastasis may manifest more than a decade after its initial presentation and diagnosis. In this review, we discuss the clinicopathologic findings of isolated renal cell carcinoma metastases of the pancreas, with special emphasis on separating metastatic renal cell carcinoma and its various differential diagnoses in the pancreas.

Clinical Application of 18F-FDG PET in Pancreas Cancer

International Nuclear Information System (INIS)

Kang, Won Jun

2008-01-01

The prevalence of pancreas cancer is increasing. Due to difficulty in detecting early stage disease, the prognosis of pancreas cancer is known to be poor. Clinical use of FDG PET in pancreas has been reported. FDG PET showed good performance in diagnosing pancreas cancer, and is expected to be useful in staging and detecting recurrence

File list: Unc.Pan.10.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Pan.10.AllAg.Pancreas mm9 Unclassified Pancreas Pancreas SRX1125784,SRX1125785,...1125798 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Pan.10.AllAg.Pancreas.bed ...

File list: Unc.Pan.20.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Pan.20.AllAg.Pancreas mm9 Unclassified Pancreas Pancreas SRX1125784,SRX1125785,...1125798 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Pan.20.AllAg.Pancreas.bed ...

File list: Unc.Pan.50.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Pan.50.AllAg.Pancreas mm9 Unclassified Pancreas Pancreas SRX1125784,SRX1125785,...1125791 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Pan.50.AllAg.Pancreas.bed ...

Endosonographic Features of Histologically Proven Gastric Ectopic Pancreas

Directory of Open Access Journals (Sweden)

Jen-Wei Chou

2014-01-01

Full Text Available Gastric ectopic pancreas is an uncommon developmental anomaly and its histological diagnosis is usually difficult by using a conventional biopsy forceps. In the literature, most cases of gastric ectopic pancreas were usually diagnosed by gross pattern during endoscopic examination or features of endoscopic ultrasound. In contrast, this disease was seldom diagnosed by histology in clinical practice. Although the typical endoscopic ultrasonographic features of ectopic pancreas include heterogeneous echogenicity, indistinct borders, and a location within 2 or more layers, it can also exhibit hypoechoic homogeneous echogenicity and a distinct border within the fourth sonographic layer (muscularis propria similar to the endoscopic ultrasonographic features of gastrointestinal stromal tumors. In our study, we found that 53% of gastric ectopic pancreas originated within the fourth sonographic layer, demonstrating hypoechoic, homogeneous echogenicity, and distinct borders. Therefore, recognizing endoscopic ultrasonographic features, combining with deep biopsy, endoscopic ultrasound-guided fine needle aspiration/core needle biopsy can prevent conducting unnecessary resection. Surgical resection is the mainstay treatment for symptomatic gastric ectopic pancreas, but endoscopic resection using endoscopic mucosal resection or endoscopic submucosal dissection technique provides an alternative method of removing superficial-type and deep-type gastric ectopic pancreas.

Result of radiation therapy for inoperable pancreas cancer

International Nuclear Information System (INIS)

Okawa, Tomohiko; Ikeda, Michio; Tazaki, Eisei; Kaneda, Koichi; Tsuya, Akira.

1978-01-01

Twenty cases of the pancreas cancer were treated by means of 60 Co γ or Linac x-rays during the period between 1958 and 1977 at the Cancer Institute Hospital and Tokyo Women's Medical College. 11 were irradiated by external radiation and 9 by intraoperative radiation. Pancreas irradiation was indicated for relief of pain and alleviation of jaundice although the effect was symptomatic. 2500 rad of intraoperative radiation was reasonable dose in about 10 x 10 cm radiation field. Radical curative irradiation for pancreas cancer might be rarely indicated. Radiotherapy of pancreas cancer should be considered in conjunction with multimodal treatment in the future. (author)

File list: Unc.Pan.05.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Pan.05.AllAg.Pancreas mm9 Unclassified Pancreas Pancreas SRX527836,SRX1125784,S...X527839 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Pan.05.AllAg.Pancreas.bed ...

Giant serous microcystic pancreas adenoma

Directory of Open Access Journals (Sweden)

Mustafa Kerem

2012-10-01

Full Text Available Serous cystadenomas are rare tumors comprising 1-2% of exocrine pancreas tumors. They are mostly known as benign conditions but malign transformation as serous cystadenocarcinoma is also reported. It is usually seen in females. Non-specific symptoms, such as abdominal pain or symptoms due to mass affect, are usually seen. A 64-year old female patient was investigated for abdominal pain. Physical and laboratory findings were normal. Abdomen ultrasonography confirmed an 11x9.5 cm solid cystic lesion and abdomen computed tomography scan confirmed a 12x11 cm lobulated cystic solid lesion which had central cystic necrotic areas extending from liver hilus inferiorly. Fine needle biopsy confirmed benign cytology and trucut biopsy of the pan creatic mass reported chronic inflamation. Nevertheless, this mass could have malignant contents and transformation potential. A laparatomy was decided due to patient’s symptoms and mass effect. Due to vascular invasion of the tumor, Whipple procedure was performed. The pathology report confirmed serous microcystic adenoma. These rare tumors are usually benign but pre-operative malignity criterias are not identified. There are few differential diagnostic tools for excluding malignity. We suggest surgical resection as best treatment approach for selected cases.

Hippo Signaling Regulates Pancreas Development through Inactivation of Yap

Science.gov (United States)

Day, Caroline E.; Boerner, Brian P.; Johnson, Randy L.; Sarvetnick, Nora E.

2012-01-01

The mammalian pancreas is required for normal metabolism, with defects in this vital organ commonly observed in cancer and diabetes. Development must therefore be tightly controlled in order to produce a pancreas of correct size, cell type composition, and physiologic function. Through negative regulation of Yap-dependent proliferation, the Hippo kinase cascade is a critical regulator of organ growth. To investigate the role of Hippo signaling in pancreas biology, we deleted Hippo pathway components in the developing mouse pancreas. Unexpectedly, the pancreas from Hippo-deficient offspring was reduced in size, with defects evident throughout the organ. Increases in the dephosphorylated nuclear form of Yap are apparent throughout the exocrine compartment and correlate with increases in levels of cell proliferation. However, the mutant exocrine tissue displays extensive disorganization leading to pancreatitis-like autodigestion. Interestingly, our results suggest that Hippo signaling does not directly regulate the pancreas endocrine compartment as Yap expression is lost following endocrine specification through a Hippo-independent mechanism. Altogether, our results demonstrate that Hippo signaling plays a crucial role in pancreas development and provide novel routes to a better understanding of pathological conditions that affect this organ. PMID:23071096

Mice with humanized liver endothelium

NARCIS (Netherlands)

el Filali, E.

2014-01-01

The only curative treatment option for a large proportion of patients suffering from a liver disorder is liver transplantation. The use of ex vivo genetically modified autologous liver cells instead of whole liver transplantation could overcome the problem of donor scarcity. Even though clinical

Chimeric mice with humanized liver: Application in drug metabolism and pharmacokinetics studies for drug discovery.

Science.gov (United States)

Naritomi, Yoichi; Sanoh, Seigo; Ohta, Shigeru

2018-02-01

Predicting human drug metabolism and pharmacokinetics (PK) is key to drug discovery. In particular, it is important to predict human PK, metabolite profiles and drug-drug interactions (DDIs). Various methods have been used for such predictions, including in vitro metabolic studies using human biological samples, such as hepatic microsomes and hepatocytes, and in vivo studies using experimental animals. However, prediction studies using these methods are often inconclusive due to discrepancies between in vitro and in vivo results, and interspecies differences in drug metabolism. Further, the prediction methods have changed from qualitative to quantitative to solve these issues. Chimeric mice with humanized liver have been developed, in which mouse liver cells are mostly replaced with human hepatocytes. Since human drug metabolizing enzymes are expressed in the liver of these mice, they are regarded as suitable models for mimicking the drug metabolism and PK observed in humans; therefore, these mice are useful for predicting human drug metabolism and PK. In this review, we discuss the current state, issues, and future directions of predicting human drug metabolism and PK using chimeric mice with humanized liver in drug discovery. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Proteomic profiling in incubation medium of mouse, rat and human precision-cut liver slices for biomarker detection regarding acute drug-induced liver injury

NARCIS (Netherlands)

van Swelm, Rachel P L; Hadi, Mackenzie; Laarakkers, Coby M M; Masereeuw, R.|info:eu-repo/dai/nl/155644033; Groothuis, Geny M M; Russel, Frans G M

Drug-induced liver injury is one of the leading causes of drug withdrawal from the market. In this study, we investigated the applicability of protein profiling of the incubation medium of human, mouse and rat precision-cut liver slices (PCLS) exposed to liver injury-inducing drugs for biomarker

Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas

OpenAIRE

Saisho, Yoshifumi

2016-01-01

The pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the ...

The Miracle of an Artificial Pancreas | NIH MedlinePlus the Magazine

Science.gov (United States)

... Diabetes Follow us The Miracle of an Artificial Pancreas Four NIH-funded Artificial Pancreas Research Efforts Underway Thanks to investments in new ... diabetes are on the horizon, including the artificial pancreas. The artificial pancreas is an integrated system that ...

Endoscopic findings following retroperitoneal pancreas transplantation.

Science.gov (United States)

Pinchuk, Alexey V; Dmitriev, Ilya V; Shmarina, Nonna V; Teterin, Yury S; Balkarov, Aslan G; Storozhev, Roman V; Anisimov, Yuri A; Gasanov, Ali M

2017-07-01

An evaluation of the efficacy of endoscopic methods for the diagnosis and correction of surgical and immunological complications after retroperitoneal pancreas transplantation. From October 2011 to March 2015, 27 patients underwent simultaneous retroperitoneal pancreas-kidney transplantation (SPKT). Diagnostic oesophagogastroduodenoscopy (EGD) with protocol biopsy of the donor and recipient duodenal mucosa and endoscopic retrograde pancreatography (ERP) were performed to detect possible complications. Endoscopic stenting of the main pancreatic duct with plastic stents and three-stage endoscopic hemostasis were conducted to correct the identified complications. Endoscopic methods showed high efficiency in the timely diagnosis and adequate correction of complications after retroperitoneal pancreas transplantation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

File list: ALL.Pan.50.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Pan.50.AllAg.Pancreas mm9 All antigens Pancreas Pancreas SRX111395,ERX651337,SR...ERX383750,SRX672452 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Pan.50.AllAg.Pancreas.bed ...

File list: ALL.Pan.10.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Pan.10.AllAg.Pancreas mm9 All antigens Pancreas Pancreas SRX111395,ERX651337,SR...ERX383754,ERX383752 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Pan.10.AllAg.Pancreas.bed ...

File list: ALL.Pan.05.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Pan.05.AllAg.Pancreas mm9 All antigens Pancreas Pancreas ERX651337,SRX527836,SR...ERX383754,ERX383752 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Pan.05.AllAg.Pancreas.bed ...

File list: ALL.Pan.20.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Pan.20.AllAg.Pancreas mm9 All antigens Pancreas Pancreas SRX111395,ERX651337,SR...ERX383750,SRX672452 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Pan.20.AllAg.Pancreas.bed ...

Sonographic evaluation of retroperitoneal pancreas transplants and their complications

International Nuclear Information System (INIS)

Rao, B.K.; Rosnberg, R.; McDermott, J.C.; Sollinger, H.W.; Belzer, F.O.

1986-01-01

Pancreas transplantation is an experimental procedure performed to restore insulin secretion in patients with diabetes mellitus. The authors reviewed 65 real-time sonograms in 42 kidney transplant recipients who also had a homologous pancreas transplanted into the retroperitoneum. Sonograms were analyzed for size of the pancreas transplant, its echo texture, size of the pancreatic duct, fluid collections around the pancreas transplant, vascular pulsations, and anastomotic site between the pancreatic duct and the urinary bladder. A normal pancreas transplant is moderately echogenic and may have small hypoechoic areas (possibly representing fibrosis or infarcts) in the early postsurgical period (based on findings in 14 of 42 patients). Dilation of the pancreatic duct (3-9 mm) and air in the pancreatic duct were common postoperatively. Pancreatitis was also common (36 patients) and was recognized by an increase in the size of the pancreas transplant and by a focally or diffusely hypoechoic texture. Rejection of the pancreas transplant was uncommon (six patients) and was detected on the basis of reduced vascular flow, an increase in size of the pancreas transplant, and a nonhomogeneous echotexture. Infraction of the transplant was rare and had an irregular, nonhomogeneously hypoechoic appearance (two patients). Seromas (eight patients), abscesses (three), and hematomas (two) were detected on the basis of septa, floating debris, mural nodules, and irregular thick walls. Enzymatic fat necrosis was recognized from floating echogenic fat debris (two patients). Air-containing abscesses were identified and confirmed on CT or US-guided aspiration (three patients). US was extremely useful for detecting, localizing, and characterizing fluid collections and provided guidance for aspiration. It is the imaging modality of choice for screening pancreas transplant recipients for postoperative changes

Protocol for Isolation of Primary Human Hepatocytes and Corresponding Major Populations of Non-parenchymal Liver Cells

Science.gov (United States)

Pfeiffer, Elisa; Zeilinger, Katrin; Seehofer, Daniel; Damm, Georg

2016-01-01

Beside parenchymal hepatocytes, the liver consists of non-parenchymal cells (NPC) namely Kupffer cells (KC), liver endothelial cells (LEC) and hepatic Stellate cells (HSC). Two-dimensional (2D) culture of primary human hepatocyte (PHH) is still considered as the "gold standard" for in vitro testing of drug metabolism and hepatotoxicity. It is well-known that the 2D monoculture of PHH suffers from dedifferentiation and loss of function. Recently it was shown that hepatic NPC play a central role in liver (patho-) physiology and the maintenance of PHH functions. Current research focuses on the reconstruction of in vivo tissue architecture by 3D- and co-culture models to overcome the limitations of 2D monocultures. Previously we published a method to isolate human liver cells and investigated the suitability of these cells for their use in cell cultures in Experimental Biology and Medicine1. Based on the broad interest in this technique the aim of this article was to provide a more detailed protocol for the liver cell isolation process including a video, which will allow an easy reproduction of this technique. Human liver cells were isolated from human liver tissue samples of surgical interventions by a two-step EGTA/collagenase P perfusion technique. PHH were separated from the NPC by an initial centrifugation at 50 x g. Density gradient centrifugation steps were used for removal of dead cells. Individual liver cell populations were isolated from the enriched NPC fraction using specific cell properties and cell sorting procedures. Beside the PHH isolation we were able to separate KC, LEC and HSC for further cultivation. Taken together, the presented protocol allows the isolation of PHH and NPC in high quality and quantity from one donor tissue sample. The access to purified liver cell populations could allow the creation of in vivo like human liver models. PMID:27077489

File list: ALL.Pan.05.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Pan.05.AllAg.Pancreas hg19 All antigens Pancreas Pancreas SRX347280,SRX134735,S...71,SRX342269,SRX188948,SRX188958 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Pan.05.AllAg.Pancreas.bed ...

File list: ALL.Pan.20.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Pan.20.AllAg.Pancreas hg19 All antigens Pancreas Pancreas SRX136972,ERX103432,S...58,SRX188948,SRX270968,SRX347271 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Pan.20.AllAg.Pancreas.bed ...

File list: ALL.Pan.10.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Pan.10.AllAg.Pancreas hg19 All antigens Pancreas Pancreas SRX136972,SRX136967,S...71,SRX342269,SRX188948,SRX188958 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Pan.10.AllAg.Pancreas.bed ...

MR imaging of the normal pancreas

International Nuclear Information System (INIS)

Itoh, Hisao; Takahashi, Norio; Uchida, Yoshie; Nakayama, Gen; Bito, Kaoru; Haba, Hirotsugu; Kawamura, Masashi; Kataoka, Masaaki; Hamamoto, Ken.

1989-01-01

To evaluate current 1.5-T MR imaging with respiratory ordered phase encoding (ROPE) technique in the identification of pancreatic contour and main pancreatic duct, 100 normal subjects examined with spin echo technique including transaxial scans of T 1 -WI,T 2 -WI, and proton density (PD)-WI were reviewed. The results of MR imaging were then compared with computed tomography (CT). Pancreatic contour was divided into 3 parts; head, body, and tail. T 1 -WI was the best pulse sequence in describing pancreas and the rates of specific identification of head, body, and tail were 69%, 97%, and 92%, respectively. While these rates were 62%, 90%, and 92% with plain CT and 69%, 94%, and 94% with contrast-enhanced CT, respectively. A combination of MR imaging and CT yielded better rates of identification. The main pancreatic duct was visible in 44% as a low intensity line on T 1 -WI and in 16% on plain CT. Dorsal to pancreas, all of the major vessels were seen in every patients. Ventrally, retroperitoneal fat was important, however, it was not a limiting factor. When respiratory compensation using ROPE functioned well, it was possible to differentiate bowel from pancreas in patients with sparse fat because signal intensity of the pancreas tended to be higher than that of gastrointestinal wall and its contents on T 1 -WI. Current MR imaging seemed to be a complementary method with CT in the identification of the pancreas. (author)

Fialuridine induces acute liver failure in chimeric TK-NOG mice: a model for detecting hepatic drug toxicity prior to human testing.

Directory of Open Access Journals (Sweden)

Dan Xu

2014-04-01

Full Text Available Seven of 15 clinical trial participants treated with a nucleoside analogue (fialuridine [FIAU] developed acute liver failure. Five treated participants died, and two required a liver transplant. Preclinical toxicology studies in mice, rats, dogs, and primates did not provide any indication that FIAU would be hepatotoxic in humans. Therefore, we investigated whether FIAU-induced liver toxicity could be detected in chimeric TK-NOG mice with humanized livers.Control and chimeric TK-NOG mice with humanized livers were treated orally with FIAU 400, 100, 25, or 2.5 mg/kg/d. The response to drug treatment was evaluated by measuring plasma lactate and liver enzymes, by assessing liver histology, and by electron microscopy. After treatment with FIAU 400 mg/kg/d for 4 d, chimeric mice developed clinical and serologic evidence of liver failure and lactic acidosis. Analysis of liver tissue revealed steatosis in regions with human, but not mouse, hepatocytes. Electron micrographs revealed lipid and mitochondrial abnormalities in the human hepatocytes in FIAU-treated chimeric mice. Dose-dependent liver toxicity was detected in chimeric mice treated with FIAU 100, 25, or 2.5 mg/kg/d for 14 d. Liver toxicity did not develop in control mice that were treated with the same FIAU doses for 14 d. In contrast, treatment with another nucleotide analogue (sofosbuvir 440 or 44 mg/kg/d po for 14 d, which did not cause liver toxicity in human trial participants, did not cause liver toxicity in mice with humanized livers.FIAU-induced liver toxicity could be readily detected using chimeric TK-NOG mice with humanized livers, even when the mice were treated with a FIAU dose that was only 10-fold above the dose used in human participants. The clinical features, laboratory abnormalities, liver histology, and ultra-structural changes observed in FIAU-treated chimeric mice mirrored those of FIAU-treated human participants. The use of chimeric mice in preclinical toxicology

Fialuridine induces acute liver failure in chimeric TK-NOG mice: a model for detecting hepatic drug toxicity prior to human testing.

Science.gov (United States)

Xu, Dan; Nishimura, Toshi; Nishimura, Sachiko; Zhang, Haili; Zheng, Ming; Guo, Ying-Ying; Masek, Marylin; Michie, Sara A; Glenn, Jeffrey; Peltz, Gary

2014-04-01

Seven of 15 clinical trial participants treated with a nucleoside analogue (fialuridine [FIAU]) developed acute liver failure. Five treated participants died, and two required a liver transplant. Preclinical toxicology studies in mice, rats, dogs, and primates did not provide any indication that FIAU would be hepatotoxic in humans. Therefore, we investigated whether FIAU-induced liver toxicity could be detected in chimeric TK-NOG mice with humanized livers. Control and chimeric TK-NOG mice with humanized livers were treated orally with FIAU 400, 100, 25, or 2.5 mg/kg/d. The response to drug treatment was evaluated by measuring plasma lactate and liver enzymes, by assessing liver histology, and by electron microscopy. After treatment with FIAU 400 mg/kg/d for 4 d, chimeric mice developed clinical and serologic evidence of liver failure and lactic acidosis. Analysis of liver tissue revealed steatosis in regions with human, but not mouse, hepatocytes. Electron micrographs revealed lipid and mitochondrial abnormalities in the human hepatocytes in FIAU-treated chimeric mice. Dose-dependent liver toxicity was detected in chimeric mice treated with FIAU 100, 25, or 2.5 mg/kg/d for 14 d. Liver toxicity did not develop in control mice that were treated with the same FIAU doses for 14 d. In contrast, treatment with another nucleotide analogue (sofosbuvir 440 or 44 mg/kg/d po) for 14 d, which did not cause liver toxicity in human trial participants, did not cause liver toxicity in mice with humanized livers. FIAU-induced liver toxicity could be readily detected using chimeric TK-NOG mice with humanized livers, even when the mice were treated with a FIAU dose that was only 10-fold above the dose used in human participants. The clinical features, laboratory abnormalities, liver histology, and ultra-structural changes observed in FIAU-treated chimeric mice mirrored those of FIAU-treated human participants. The use of chimeric mice in preclinical toxicology studies could improve

File list: Oth.Pan.05.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Pan.05.AllAg.Pancreas mm9 TFs and others Pancreas Pancreas SRX111395,SRX672451,...ERX383750,ERX383751,ERX383754,ERX383752 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Pan.05.AllAg.Pancreas.bed ...

File list: Oth.Pan.10.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Pan.10.AllAg.Pancreas mm9 TFs and others Pancreas Pancreas SRX111395,SRX672451,...ERX383750,ERX383751,ERX383754,ERX383752 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Pan.10.AllAg.Pancreas.bed ...

File list: Oth.Pan.20.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Pan.20.AllAg.Pancreas mm9 TFs and others Pancreas Pancreas SRX111395,SRX672451,...ERX383752,ERX383751,ERX383754,ERX383750 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Pan.20.AllAg.Pancreas.bed ...

File list: Oth.Pan.50.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Pan.50.AllAg.Pancreas mm9 TFs and others Pancreas Pancreas SRX111395,SRX672451,...ERX383752,ERX383751,ERX383754,ERX383750 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Pan.50.AllAg.Pancreas.bed ...

MicroRNA-mediated suppression of oncolytic adenovirus replication in human liver.

Directory of Open Access Journals (Sweden)

Erkko Ylösmäki

Full Text Available MicroRNAs (miRNAs are important and ubiquitous regulators of gene expression that can suppress their target genes by translational inhibition as well as mRNA destruction. Cell type-specific miRNA expression patterns have been successfully exploited for targeting the expression of experimental and therapeutic gene constructs, for example to reduce pathogenic effects of cancer virotherapy in normal tissues. In order to avoid liver damage associated with systemic or intrahepatic delivery of oncolytic adenoviruses we have introduced the concept of suppressing adenovirus replication in hepatic cells by inserting target elements for the liver-specific miR122 into the viral genome. Here we show using ex vivo cultured tissue specimens that six perfectly complementary miR122 target sites in the 3' untranslated region of the viral E1A gene are sufficient in the absence of any other genetic modifications to prevent productive replication of serotype 5 adenovirus (Ad5 in normal human liver. This modification did not compromise the replicative capacity of the modified virus in cancer tissue derived from a colon carcinoma liver metastasis or its oncolytic potency in a human lung cancer xenograft mouse model. Unlike wild-type Ad5, the modified virus did not result in increased serum levels of liver enzymes in infected mice. These results provide a strong preclinical proof of concept for the use of miR122 target sites for reducing the risk of liver damage caused by oncolytic adenoviruses, and suggest that ectopic miR122 target elements should be considered as an additional safety measure included in any therapeutic virus or viral vector posing potential hazard to the liver.

The pancreas responds to remote damage and systemic stress by secretion of the pancreatic secretory proteins PSP/regI and PAP/regIII.

Science.gov (United States)

Reding, Theresia; Palmiere, Cristian; Pazhepurackel, Clinsyjos; Schiesser, Marc; Bimmler, Daniel; Schlegel, Andrea; Süss, Ursula; Steiner, Sabrina; Mancina, Leandro; Seleznik, Gitta; Graf, Rolf

2017-05-02

In patients with infection and sepsis serum levels of Pancreatic Stone protein/regenerating protein I (PSP) are highly elevated. The origin of PSP during these conditions is presumably the pancreas, however, an intestinal origin cannot be excluded. Similarly, pancreatitis-associated protein (PAP) was identified in the pancreas. These proteins were also localized in intestinal organs. Here we aim to elucidate the bio-distribution of PSP and PAP in animal models of sepsis and in healthy humans. PSP and PAP responded to remote lesions in rats although the pancreatic response was much more pronounced than the intestinal. Tissue distribution of PSP demonstrated a 100-fold higher content in the pancreas compared to any other organ while PAP was most abundant in the small intestine. Both proteins responded to CLP or sham operation in the pancreas. PSP also increased in the intestine during CLP. The distribution of PSP and PAP in human tissue mirrored the distribution in the murine models. Distribution of PSP and PAP was visualized by immunohistochemistry. Rats and mice underwent midline laparotomies followed by mobilization of tissue and incision of the pancreatic duct or duodenum. Standard cecum-ligation-puncture (CLP) procedures or sham laparotomies were performed. Human tissue extracts were analyzed for PSP and PAP. The pancreas reacts to remote lesions and septic insults in mice and rats with increased PSP synthesis, while PAP is selectively responsive to septic events. Furthermore, our results suggest that serum PSP in septic patients is predominantly derived through an acute phase response of the pancreas.

Solitary Fibrous Tumor of the Pancreas: Imaging Findings

International Nuclear Information System (INIS)

Kwon, Heon Ju; Byun, Jae Ho; Kang, Jun; Park, Seong Ho; Lee, Moon Gyu

2008-01-01

We report here a case of a pathologically proven solitary fibrous tumor of the pancreas. A 54-year-old man was referred to our hospital for further evaluation of a pancreatic mass that was found incidentally. CT, MR imaging, and endoscopic ultrasonography showed a well-defined, enhancing mass with cystic portions of the pancreas body. MR cholangiopancreatography showed no pancreatic duct dilatation. A solitary fibrous tumor of the pancreas is a very rare lesion

Primary hydatid cysts of the pancreas

African Journals Online (AJOL)

Kurt

Hydatid cysts of the pancreas are rare. The reported incidence varies from 0.1% to 2% of patients with hydatid disease.4-7. Management may be diffi- cult as a hydatid cyst in the head of the pancreas may closely simulate a cystic tumour. In this study we report 4 cases of primary hydatid cysts involving the head of the ...

Heterotopic Pancreas: Histopathologic Features, Imaging Findings, and Complications.

Science.gov (United States)

Rezvani, Maryam; Menias, Christine; Sandrasegaran, Kumaresan; Olpin, Jeffrey D; Elsayes, Khaled M; Shaaban, Akram M

2017-01-01

Heterotopic pancreas is a congenital anomaly in which pancreatic tissue is anatomically separate from the main gland. The most common locations of this displacement include the upper gastrointestinal tract-specifically, the stomach, duodenum, and proximal jejunum. Less common sites are the esophagus, ileum, Meckel diverticulum, biliary tree, mesentery, and spleen. Uncomplicated heterotopic pancreas is typically asymptomatic, with the lesion being discovered incidentally during an unrelated surgery, during an imaging examination, or at autopsy. The most common computed tomographic appearance of heterotopic pancreas is that of a small oval intramural mass with microlobulated margins and an endoluminal growth pattern. The attenuation and enhancement characteristics of these lesions parallel their histologic composition. Acinus-dominant lesions demonstrate avid homogeneous enhancement after intravenous contrast material administration, whereas duct-dominant lesions are hypovascular and heterogeneous. At magnetic resonance imaging, the heterotopic pancreas is isointense to the orthotopic pancreas, with characteristic T1 hyperintensity and early avid enhancement after intravenous gadolinium-based contrast material administration. Heterotopic pancreatic tissue has a rudimentary ductal system in which an orifice is sometimes visible at imaging as a central umbilication of the lesion. Complications of heterotopic pancreas include pancreatitis, pseudocyst formation, malignant degeneration, gastrointestinal bleeding, bowel obstruction, and intussusception. Certain complications may be erroneously diagnosed as malignancy. Paraduodenal pancreatitis is thought to be due to cystic degeneration of heterotopic pancreatic tissue in the medial wall of the duodenum. Recognizing the characteristic imaging features of heterotopic pancreas aids in differentiating it from cancer and thus in avoiding unnecessary surgery. © RSNA, 2017.

In vitro pancreas organogenesis from dispersed mouse embryonic progenitors

DEFF Research Database (Denmark)

Greggio, Chiara; De Franceschi, Filippo; Figueiredo-Larsen, Evan Manuel

2014-01-01

The pancreas is an essential organ that regulates glucose homeostasis and secretes digestive enzymes. Research on pancreas embryogenesis has led to the development of protocols to produce pancreatic cells from stem cells (1). The whole embryonic organ can be cultured at multiple stages...... expanding progenitors and differentiate into endocrine, acinar and ductal cells and which spontaneously self-organize to resemble the embryonic pancreas. We show here that the in vitro process recapitulates many aspects of natural pancreas development. This culture system is suitable to investigate how...... cells cooperate to form an organ by reducing its initial complexity to few progenitors. It is a model that reproduces the 3D architecture of the pancreas and that is therefore useful to study morphogenesis, including polarization of epithelial structures and branching. It is also appropriate to assess...

Betatrophin: A liver-derived hormone for the pancreatic β-cell proliferation.

Science.gov (United States)

Raghow, Rajendra

2013-12-15

The pancreatic β-cell failure which invariably accompanies insulin resistance in the liver and skeletal muscle is a hallmark of type-2 diabetes mellitus (T2DM). The persistent hyperglycemia of T2DM is often treated with anti-diabetic drugs with or without subcutaneous insulin injections, neither of which mimic the physiological glycemic control seen in individuals with fully functional pancreas. A sought after goal for the treatment of T2DM has been to harness the regenerative potential of pancreatic β-cells that might obviate a need for exogenous insulin injections. A new study towards attaining this aim was reported by Yi et al, who have characterized a liver-derived protein, named betatrophin, capable of inducing pancreatic β-cell proliferation in mice. Using a variety of in vitro and in vivo methods, Yi et al, have shown that betatrophin was expressed mainly in the liver and adipose tissue of mice. Exogenous expression of betatrophin in the liver led to dramatic increase in the pancreatic β-cell mass and higher output of insulin in mice that also concomitantly elicited improved glucose tolerance. The authors discovered that betatrophin was also present in the human plasma. Surprisingly, betatrophin has been previously described by three other names, i.e., re-feeding-induced fat and liver protein, lipasin and atypical angiopoeitin-like 8, by three independent laboratories, as nutritionally regulated liver-enriched factors that control serum triglyceride levels and lipid metabolism. Yi et al demonstration of betatrophin, as a circulating hormone that regulates β-cell proliferation, if successfully translated in the clinic, holds the potential to change the course of current therapies for diabetes.

Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers

Directory of Open Access Journals (Sweden)

Claudia Sanna

2016-05-01

Full Text Available Non-alcoholic fatty liver disease (NAFLD is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas and extra-intestinal sites (kidney in men, and breast in women. Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC, but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites.

Ectopic pancreas with pseudocyst and pseudoaneurysm formation

International Nuclear Information System (INIS)

Surov, A.; Hainz, M.; Hinz, L.; Holzhausen, H.-J.; Finke, R.; Spielmann, R.-P.; Kunze, C.

2009-01-01

Ectopic pancreas is a rare congenital anomaly. It is usually asymptomatic, or presents with non specific gastrointestinal symptoms. We describe here a case of ectopic pancreas in the gastric antrum, with pseudocyst and pseudoaneurysm formation. This entity has not been reported previously in the literature.

Hepatic iron overload following liver transplantation of a C282y homozygous allograft: a case report and literature review.

LENUS (Irish Health Repository)

Dwyer, Jeremy P

2011-11-01

Hereditary haemochromatosis is a common genetic disease associated with progressive iron overload and parenchymal organ damage including liver, pancreas and heart. We report a case of inadvertent transplantation of a liver from a haemochromatosis donor to a 56-year-old Asian female. Progressive iron overload occurred over a 2 year follow up as assessed by liver biopsy and iron studies in the absence of a secondary cause of iron overload, supporting a primary role of liver rather than small intestine in the regulation of iron homeostasis in hereditary haemochromatosis.

Expanding the indications of pancreas transplantation alone.

Science.gov (United States)

Mehrabi, Arianeb; Golriz, Mohammad; Adili-Aghdam, Fatemeh; Hafezi, Mohammadreza; Ashrafi, Maryam; Morath, Christian; Zeier, Martin; Hackert, Thilo; Schemmer, Peter

2014-11-01

Total pancreatectomy (TP) is associated with postoperative endocrine and exocrine insufficiency. Especially, insulin therapy reduces quality of life and may lead to long-term complications. We review the literature with regard to the potential option of pancreas transplantation alone (PTA) after TP in patients with chronic pancreatitis or benign tumors. A MEDLINE search (1958-2013) using the terminologies pancreas transplantation, pancreas transplantation alone, total pancreatectomy, morbidity, mortality, insulin therapy, and quality of life was performed. In addition, the current book and congress publications were reviewed. Total pancreatectomy after benign and borderline tumors as well as chronic pancreatitis is continuously increasing. Despite improvement of exogenous insulin therapy, more than 50% of these patients experience severe glucose control problems, which cause up to 50% long-term mortality. Pancreas transplantation alone can cure both endocrine and exocrine insufficiency and reduce the associated risks. The 3-year graft and patient survival rates after PTA are up to 73% and 100%, respectively. Pancreas transplantation alone after TP in patients with pancreatitis or benign tumors improves the recipient's quality of life and reduces long-term mortality. Considering the amount of available organs and potential candidates, PTA can be a treatment option for patients after TP with chronic pancreatitis or benign tumors.

TU-F-BRF-06: 3D Pancreas MRI Segmentation Using Dictionary Learning and Manifold Clustering

International Nuclear Information System (INIS)

Gou, S; Rapacchi, S; Hu, P; Sheng, K

2014-01-01

Purpose: The recent advent of MRI guided radiotherapy machines has lent an exciting platform for soft tissue target localization during treatment. However, tools to efficiently utilize MRI images for such purpose have not been developed. Specifically, to efficiently quantify the organ motion, we develop an automated segmentation method using dictionary learning and manifold clustering (DLMC). Methods: Fast 3D HASTE and VIBE MR images of 2 healthy volunteers and 3 patients were acquired. A bounding box was defined to include pancreas and surrounding normal organs including the liver, duodenum and stomach. The first slice of the MRI was used for dictionary learning based on mean-shift clustering and K-SVD sparse representation. Subsequent images were iteratively reconstructed until the error is less than a preset threshold. The preliminarily segmentation was subject to the constraints of manifold clustering. The segmentation results were compared with the mean shift merging (MSM), level set (LS) and manual segmentation methods. Results: DLMC resulted in consistently higher accuracy and robustness than comparing methods. Using manual contours as the ground truth, the mean Dices indices for all subjects are 0.54, 0.56 and 0.67 for MSM, LS and DLMC, respectively based on the HASTE image. The mean Dices indices are 0.70, 0.77 and 0.79 for the three methods based on VIBE images. DLMC is clearly more robust on the patients with the diseased pancreas while LS and MSM tend to over-segment the pancreas. DLMC also achieved higher sensitivity (0.80) and specificity (0.99) combining both imaging techniques. LS achieved equivalent sensitivity on VIBE images but was more computationally inefficient. Conclusion: We showed that pancreas and surrounding normal organs can be reliably segmented based on fast MRI using DLMC. This method will facilitate both planning volume definition and imaging guidance during treatment

TU-F-BRF-06: 3D Pancreas MRI Segmentation Using Dictionary Learning and Manifold Clustering

Energy Technology Data Exchange (ETDEWEB)

Gou, S; Rapacchi, S; Hu, P; Sheng, K [UCLA School of Medicine, Los Angeles, CA (United States)

2014-06-15

Purpose: The recent advent of MRI guided radiotherapy machines has lent an exciting platform for soft tissue target localization during treatment. However, tools to efficiently utilize MRI images for such purpose have not been developed. Specifically, to efficiently quantify the organ motion, we develop an automated segmentation method using dictionary learning and manifold clustering (DLMC). Methods: Fast 3D HASTE and VIBE MR images of 2 healthy volunteers and 3 patients were acquired. A bounding box was defined to include pancreas and surrounding normal organs including the liver, duodenum and stomach. The first slice of the MRI was used for dictionary learning based on mean-shift clustering and K-SVD sparse representation. Subsequent images were iteratively reconstructed until the error is less than a preset threshold. The preliminarily segmentation was subject to the constraints of manifold clustering. The segmentation results were compared with the mean shift merging (MSM), level set (LS) and manual segmentation methods. Results: DLMC resulted in consistently higher accuracy and robustness than comparing methods. Using manual contours as the ground truth, the mean Dices indices for all subjects are 0.54, 0.56 and 0.67 for MSM, LS and DLMC, respectively based on the HASTE image. The mean Dices indices are 0.70, 0.77 and 0.79 for the three methods based on VIBE images. DLMC is clearly more robust on the patients with the diseased pancreas while LS and MSM tend to over-segment the pancreas. DLMC also achieved higher sensitivity (0.80) and specificity (0.99) combining both imaging techniques. LS achieved equivalent sensitivity on VIBE images but was more computationally inefficient. Conclusion: We showed that pancreas and surrounding normal organs can be reliably segmented based on fast MRI using DLMC. This method will facilitate both planning volume definition and imaging guidance during treatment.

Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1.

Science.gov (United States)

Gueguen, M; Yamamoto, A M; Bernard, O; Alvarez, F

1989-03-15

Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease.

Microcystic adenoma of the pancreas

Directory of Open Access Journals (Sweden)

Čolović Radoje B.

2002-01-01

Full Text Available Microcystic adenoma of the pancreas is a rare benign tumour of the pancreas without malignant potential which usually appears in older women. Pain weight loss, palpable mass and jaundice (if the tumor is localized in the head of the pancreas are the main symptoms. Thanks to the modern imaging techniques (US, CT, FNB the tumor is discovered and with rising frequency exactly preoperatively diagnosed. Surgical excision is the treatment of choice. In risk patients without symptoms surgery is not necessary but patients have to be regularly followed-up. The authors present a 70-year old woman in whom, because of constant epigastric pain, a multicystic mass of the pancreatic body, 58 x 40 mm in diameter, was discovered and removed by distal pancreatectomy. The spleen could not be saved. Histologic examination showed a microcystic adenoma. Three years after surgery the patient is symptom-free with normal ultra-sonographic findings.

Vasoactive intestinal polypeptide (VIP) in the pig pancreas

DEFF Research Database (Denmark)

Poulsen, Steen Seier

1984-01-01

Vasoactive intestinal polypeptide (VIP) in the pig pancreas is localized to nerves, many of which travel along the pancreatic ducts. VIP stimulates pancreatic fluid and bicarbonate secretion like secretin. Electrical vagal stimulation in the pig causes an atropine-resistant profuse secretion...... of bicarbonate-rich pancreatic juice. In an isolated perfused preparation of the pig pancreas with intact vagal nerve supply, electrical vagal stimulation caused an atropine-resistant release of VIP, which accurately parallelled the exocrine secretion of juice and bicarbonate. Perfusion of the pancreas...... with a potent VIP-antiserum inhibited the effect of vagal stimulation on the exocrine secretion. It is concluded, that VIP is responsible for (at least part of) the neurally controlled fluid and bicarbonate secretion from the pig pancreas....

Concentration and distribution of dioxins and related compounds in various human organs

Energy Technology Data Exchange (ETDEWEB)

Iida, T.; Hirakawa, H.; Hori, T.; Tobiishi, K.; Matsueda, T. [Fukuoka Inst. of Health and Environmental Sciences, Dazaifu, Fukuoka (Japan); Todaka, T. [Japan Food Hygiene Association, Tokyo (Japan); Watanabe, S. [Tokyo Univ. of Agriculture, Tokyo (Japan); Yamada, T. [Keio Univ. School of Medicine, Tokyo (Japan)

2004-09-15

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and non-ortho coplanar polychlorinated biphenyls (Non-Co-PCBs) and mono-ortho coplanar polychlorinated biphenyls (Mono-Co-PCBs) accumulate in the human body due to their highly lipophilic properties. In recent years, there has been some concern about the potential health effects of dioxins and related chemicals for the general population of humans. Although there exists an enormous amount of data on this subject, most of it is from breast milk and blood, due to ease of collection; information concerning concentrations and distribution in various human organs hardly exists. Therefore, new data concerning various human tissues is required to evaluate the pathophysiological significance of dioxins and related compounds in humans. The aim of this study was to investigate the concentration levels and distribution of dioxins and related compounds in various human organ tissues. We previously reported on the concentration levels in the human liver and adipose tissues from 28 donors. In this paper, we determined the concentrations of dioxin-like isomers in 8 organs, including blood, lungs, liver, bile, spleen, pancreas, kidney and mesentery fat from 20 donors.

A microscale human liver platform that supports the hepatic stages of Plasmodium falciparum and vivax.

Science.gov (United States)

March, Sandra; Ng, Shengyong; Velmurugan, Soundarapandian; Galstian, Ani; Shan, Jing; Logan, David J; Carpenter, Anne E; Thomas, David; Sim, B Kim Lee; Mota, Maria M; Hoffman, Stephen L; Bhatia, Sangeeta N

2013-07-17

The Plasmodium liver stage is an attractive target for the development of antimalarial drugs and vaccines, as it provides an opportunity to interrupt the life cycle of the parasite at a critical early stage. However, targeting the liver stage has been difficult. Undoubtedly, a major barrier has been the lack of robust, reliable, and reproducible in vitro liver-stage cultures. Here, we establish the liver stages for both Plasmodium falciparum and Plasmodium vivax in a microscale human liver platform composed of cryopreserved, micropatterned human primary hepatocytes surrounded by supportive stromal cells. Using this system, we have successfully recapitulated the full liver stage of P. falciparum, including the release of infected merozoites and infection of overlaid erythrocytes, as well as the establishment of small forms in late liver stages of P. vivax. Finally, we validate the potential of this platform as a tool for medium-throughput antimalarial drug screening and vaccine development. Copyright © 2013 Elsevier Inc. All rights reserved.

Vascular development in the vertebrate pancreas

Science.gov (United States)

Azizoglu, D. Berfin; Chong, Diana C.; Villasenor, Alethia; Magenheim, Judith; Barry, David M.; Lee, Simon; Marty-Santos, Leilani; Fu, Stephen; Dor, Yuval; Cleaver, Ondine

2016-01-01

The vertebrate pancreas is comprised of a highly branched tubular epithelium, which is intimately associated with an extensive and specialized vasculature. While we know a great deal about basic vascular anatomy of the adult pancreas, as well as islet capillaries, surprisingly little is known about the ontogeny of its blood vessels. Here, we analyze development of the pancreatic vasculature in the mouse embryo. We show that pancreatic epithelial branches intercalate with the fine capillary plexus of the surrounding pancreatic mesenchyme. Endothelial cells (ECs) within this mesenchyme are heterogeneous from the onset of organogenesis. Pancreatic arteries take shape before veins, in a manner analogous to early embryonic vessels. The main central artery forms during mid-gestation, as a result of vessel coalescence and remodeling of a vascular plexus. In addition, we show that vessels in the forming pancreas display a predictable architecture that is dependent on VEGF signaling. Over-expression of VEGF disrupts vascular patterning and arteriovenous differentiation within the developing pancreas. This study constitutes a first-time cellular and molecular characterization of pancreatic blood vessels, as they coordinately grow along with the pancreatic epithelium. PMID:27789228

Vascular development in the vertebrate pancreas.

Science.gov (United States)

Azizoglu, D Berfin; Chong, Diana C; Villasenor, Alethia; Magenheim, Judith; Barry, David M; Lee, Simon; Marty-Santos, Leilani; Fu, Stephen; Dor, Yuval; Cleaver, Ondine

2016-12-01

The vertebrate pancreas is comprised of a highly branched tubular epithelium, which is intimately associated with an extensive and specialized vasculature. While we know a great deal about basic vascular anatomy of the adult pancreas, as well as islet capillaries, surprisingly little is known about the ontogeny of its blood vessels. Here, we analyze development of the pancreatic vasculature in the mouse embryo. We show that pancreatic epithelial branches intercalate with the fine capillary plexus of the surrounding pancreatic mesenchyme. Endothelial cells (ECs) within this mesenchyme are heterogeneous from the onset of organogenesis. Pancreatic arteries take shape before veins, in a manner analogous to early embryonic vessels. The main central artery forms during mid-gestation, as a result of vessel coalescence and remodeling of a vascular plexus. In addition, we show that vessels in the forming pancreas display a predictable architecture that is dependent on VEGF signaling. Over-expression of VEGF disrupts vascular patterning and arteriovenous differentiation within the developing pancreas. This study constitutes a first-time in-depth cellular and molecular characterization of pancreatic blood vessels, as they coordinately grow along with the pancreatic epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

Liver Progenitor Cell Line HepaRG Differentiated in a Bioartificial Liver Effectively Supplies Liver Support to Rats with Acute Liver Failure

NARCIS (Netherlands)

Nibourg, Geert A. A.; Chamuleau, Robert A. F. M.; van der Hoeven, Tessa V.; Maas, Martinus A. W.; Ruiter, An F. C.; Lamers, Wouter H.; Oude Elferink, Ronald P. J.; van Gulik, Thomas M.; Hoekstra, Ruurdtje

2012-01-01

A major roadblock to the application of bioartificial livers is the need for a human liver cell line that displays a high and broad level of hepatic functionality. The human bipotent liver progenitor cell line HepaRG is a promising candidate in this respect, for its potential to differentiate into

Primary Extraskeletal Mesenchymal Chondrosarcoma Arising from the Pancreas

Energy Technology Data Exchange (ETDEWEB)

Oh, Bae Geun; Han, Yoon Hee; Lee, Byung Hoon; Kim, Su Young; Hwang, Yoon Joon; Seo, Jung Wook; Kim, Yong Hoon; Cha, Soon Joo; Hur, Gham; Joo, Mee [Inje University, School of Medicine, Goyang (Korea, Republic of)

2007-12-15

The CT scans showed a heterogeneously enhancing necrotic mass with numerous areas of coarse calcification, and this was located in the left side of the retroperitoneal space and involved the body and tail of the pancreas. Portal venography via the celiac axis also showed invasion of the splenic vein. It represents approximately 1% of all chondrosarcomas and it carries a poor prognosis. It can occur in extraskeletal locations and mainly in the soft tissues of the orbit, the cranial and spinal meningeal coverings and the lower limbs. To the best of our knowledge, there has been no reported case of primary extraskeletal mesenchymal chondrosarcoma of the pancreas. Only two instances of metastatic chondrosarcomas in the pancreas have been reported in the literature. We report here on a case of primary mesenchymal chondrosarcoma arising from the pancreas in a 41-year-old man. In summary, we present here a case of primary extraskeletal mesenchymal chondrosarcoma that arose from the pancreas. Radiologically, it manifested as a necrotic soft tissue mass with chondroid calcifications.

Poorly differentiated neuroendocrine carcinoma of the pancreas responsive to combination therapy with gemcitabine and S-1.

Science.gov (United States)

Yamamoto, Mitsuyoshi; Miyagawa, Koichiro; Hiura, Masaaki; Taguchi, Masashi; Kihara, Yasuyuki; Abe, Shintaro; Shimajiri, Shohei; Harada, Masaru

2012-01-01

Poorly differentiated neuroendocrine carcinoma is a very rare malignancy, but it is characterized by agressive histological features and a poor clinical prognosis. We report a 42-year-old man who had poorly differentiated neuroendocrine carcinoma of the pancreas with multiple liver metastases. We administrated combined chemotherapy with S-1 and gemcitabine. This treatment was efficacious and well tolerated, and then this patient obtained objective partial response for 7 months and survived for 13 months after the diagnosis. This case suggests that S-1 and gemcitabine combination produce beneficial responses for patients with this disease.

Production of factor VIII by human liver sinusoidal endothelial cells transplanted in immunodeficient uPA mice.

Directory of Open Access Journals (Sweden)

Marina E Fomin

Full Text Available Liver sinusoidal endothelial cells (LSECs form a semi-permeable barrier between parenchymal hepatocytes and the blood. LSECs participate in liver metabolism, clearance of pathological agents, immunological responses, architectural maintenance of the liver and synthesis of growth factors and cytokines. LSECs also play an important role in coagulation through the synthesis of Factor VIII (FVIII. Herein, we phenotypically define human LSECs isolated from fetal liver using flow cytometry and immunofluorescence microscopy. Isolated LSECs were cultured and shown to express endothelial markers and markers specific for the LSEC lineage. LSECs were also shown to engraft the liver when human fetal liver cells were transplanted into immunodeficient mice with liver specific expression of the urokinase-type plasminogen activator (uPA transgene (uPA-NOG mice. Engrafted cells expressed human Factor VIII at levels approaching those found in human plasma. We also demonstrate engraftment of adult LSECs, as well as hepatocytes, transplanted into uPA-NOG mice. We propose that overexpression of uPA provides beneficial conditions for LSEC engraftment due to elevated expression of the angiogenic cytokine, vascular endothelial growth factor. This work provides a detailed characterization of human midgestation LSECs, thereby providing the means for their purification and culture based on their expression of CD14 and CD32 as well as a lack of CD45 expression. The uPA-NOG mouse is shown to be a permissive host for human LSECs and adult hepatocytes, but not fetal hepatoblasts. Thus, these mice provide a useful model system to study these cell types in vivo. Demonstration of human FVIII production by transplanted LSECs encourages further pursuit of LSEC transplantation as a cellular therapy for the treatment of hemophilia A.

Pancreas Center Data Profile

Science.gov (United States)

... Composite Allograft Organ Transport Living Donation Informing Patients Ethics Guidance Calendar of Events Glossary Organ Procurement and Transplantation Network Pancreas Home Data Organ Datasource ...

Tachykinins in the porcine pancreas

DEFF Research Database (Denmark)

Schmidt, P T; Tornøe, K; Poulsen, Steen Seier

2000-01-01

The localization, release, and effects of substance P and neurokinin A were studied in the porcine pancreas and the localization of substance P immunoreactive nerve fibers was examined by immunohistochemistry. The effects of electrical vagus stimulation and capsaicin infusion on tachykinin release...... and the effects of substance P and neurokinin A infusion on insulin, glucagon, somatostatin, and exocrine secretion were studied using the isolated perfused porcine pancreas with intact vagal innervation. NK-1 and NK-2 receptor antagonists were used to investigate receptor involvement. Substance P immunoreactive...

Double-Balloon Catheter for Isolated Liver Perfusion: An Experimental Study

International Nuclear Information System (INIS)

Cwikiel, Wojciech; Bergqvist, Lennart; Harnek, Jan

2001-01-01

Purpose: Further development of a previously described interventional method for isolated liver perfusion (ILP) with a new double-lumen balloon catheter, and evaluation of the side-effects of such isolation.Methods: In six pigs a double-balloon occlusion catheter was placed via the transjugular approach with its tip in the portal vein. One of the balloons was positioned in the inferior vena cava (IVC), cranial to the origin of the hepatic veins and the other balloon in the portal vein. By the transfemoral approach, a single-balloon occlusion catheter was placed in the IVC caudal to the origin of the hepatic veins. A third catheter was placed by the transfemoral route with the occlusion balloon in the proper hepatic artery. After inflation of all balloons 99 Tc m -labelled human serum albumin was recirculated through the liver. The isolation was evaluated by repeated measurement of radioactivity levels in peripheral blood. Laboratory tests of liver and pancreas function, and hemoglobin, were taken before, at the end of, and 3 days after the procedure. Blood gases were tested at the beginning and end of the procedure.Results: One pig died during the procedure due to technical failure and was excluded from the study. In the other pigs leakage from the isolated liver to the systemic circulation increased slowly, up to 9.7% (mean) during 30 min of recirculation of the perfusate through the liver. Laboratory tests were normal in all pigs except insignificant acidosis directly after the procedure and the slight elevation of s-ALAT after 3 days.Conclusions: Only minor leakage from the liver to the systemic circulation was noted during ILP performed with a new, double-balloon catheter. There were no serious side effects

Pancreatic pseudocyst located in the liver Pseudoquiste pancreático de localización hepática

Directory of Open Access Journals (Sweden)

I. Les

2006-08-01

Full Text Available Pancreatic pseudocyst is a common complication of acute and chronic pancreatitis. Extrapancreatic locations of pancreatic pseudocyst in the liver, pleura, mediastinum, or pelvis have been described. However, a pancreatic pseudocyst located in the liver is an infrequent condition. We present the case of a 46-year-old man with pancreatic pseudocyst located in the liver secondary to chronic alcoholic pancreatitis. During admission, the patient underwent an abdominal CT scan that showed a mass located in the head and body of the pancreas, as well as a thrombosis of the splenic vein. A percutaneous needle aspiration biopsy of the pancreas was obtained under CT guidance, which showed no tumoral involvement. Fourty-eight hours after the procedure the patient developed abdominal pain and elevated serum amylase levels. A pancreatic MRI exam showed two pancreatic pseudocysts, one of them located in the left hepatic lobe, the other in the pancreatic tail. Chronic pancreatitis signs also were found. Enteral nutrition via a nasojejunal tube was administered for two weeks. The disappearance of the pancreatic pseudocyst located in the pancreatic tail, and a subtotal resolution of the pancreatic pseudocyst located in the liver were observed. To date twenty-seven cases of pancreatic pseudocyst located in the liver have been published, most of them managed with percutaneous or surgical drainage.

Fatty Pancreas: Should We Be Concerned?

Science.gov (United States)

Majumder, Shounak; Philip, Nissy A; Takahashi, Naoki; Levy, Michael J; Singh, Vijay P; Chari, Suresh T

The metabolic consequences of visceral fat deposition are well known, and the presence of intrapancreatic fat (IPF) has been recognized for decades. However, our knowledge about the distribution of fat in the pancreas and its clinical implications is in a nascent stage. Various terms have been proposed to describe IPF; for the purpose of this narrative review, we chose the general term fatty pancreas. Herein, we describe the radiologic, endoscopic, and histopathologic aspects of diagnosing fatty pancreas and provide an overview of the diseases associated with this condition. Our purpose is to highlight diagnostic challenges and identify specific clinical questions that would benefit from further study. As evident in this review, IPF is associated with various metabolic diseases, pancreatitis, pancreatic cancer, and precancer-yet establishing causality needs careful, further study.

Preganglionic innervation of the pancreas islet cells in the rat

NARCIS (Netherlands)

LUITEN, PGM; TERHORST, GJ; KOOPMANS, SJ; RIETBERG, M; STEFFENS, AB

1984-01-01

The position and number of preganglionic somata innervating the insulin-secreting β-cells of the endocrine pancreas were investigated in Wistar rats. This question was approached by comparing the innervation of the pancreas of normal rats with the innervation of the pancreas in alloxan-induced

Ectopic pancreas in a giant mediastinal cyst

NARCIS (Netherlands)

Li, Wilson W.; van Boven, Wim Jan; Jurhill, Roy R.; Bonta, Peter I.; Annema, Jouke T.; de Mol, Bas A.

2016-01-01

Ectopic pancreas located in the mediastium is an extremely rare anomaly. We present a case of an ectopic pancreas located in a giant mediastinal cyst in an 18-year-old man. He presented with symptoms of dyspnea due to external compression of the cyst on the left main bronchus. Complete surgical

File list: NoD.Pan.20.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Pan.20.AllAg.Pancreas mm9 No description Pancreas Pancreas ERX651337,ERX651340,...ERX651341,ERX651342 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Pan.20.AllAg.Pancreas.bed ...

File list: NoD.Pan.05.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Pan.05.AllAg.Pancreas mm9 No description Pancreas Pancreas ERX651337,ERX651340,...ERX651342,ERX651341 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Pan.05.AllAg.Pancreas.bed ...

File list: NoD.Pan.10.AllAg.Pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Pan.10.AllAg.Pancreas mm9 No description Pancreas Pancreas ERX651337,ERX651340,...ERX651342,ERX651341 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Pan.10.AllAg.Pancreas.bed ...

In ovo injection of prebiotics and synbiotics affects the digestive potency of the pancreas in growing chickens.

Science.gov (United States)

Pruszynska-Oszmalek, E; Kolodziejski, P A; Stadnicka, K; Sassek, M; Chalupka, D; Kuston, B; Nogowski, L; Mackowiak, P; Maiorano, G; Jankowski, J; Bednarczyk, M

2015-08-01

The purpose of the study was to examine the effect of 2 prebiotics and 2 synbiotics on the digestive potency of pancreas in 1-, 3-, 7-, 14-, 21-, and 34-day-old cockerels. Prebiotics (inulin and Bi²tos) and synbiotics (inulin + Lactococcus lactis subsp. lactis and Bi²tos + Lactococcus lactis subsp. cremoris) were injected in ovo into the air cell on the 12th d embryonic development. Their application increased the activity of amylase, lipase, and trypsin in the pancreas. The most pronounced changes were observed at the end of the investigated rearing period (d 34). The strongest stimulative effects on amylase were shown by both synbiotics, on lipase synbiotic Bi²tos + Lactococcus lactis subsp. cremoris, and on trypsin all the used prebiotics and synbiotics. Simultaneously, neither the absolute nor the relative mass of the pancreas in comparison to control group were changed. Also, the injected in ovo compounds did not cause a deterioration in the posthatching condition of the chicken liver, as determined by measurement of the activity of marker enzymes in the blood (alanine aminotransferase and aspartate aminotransferase). Treatment with the prebiotics and synbiotics did not change the feed conversion ratio but Bi²tos (galacto-oligosaccharide) and inulin (fructan) + Lactococcus lactis subsp. lactis significantly increased final BW. © 2015 Poultry Science Association Inc.

The draft genome of the carcinogenic human liver fluke Clonorchis sinensis

Science.gov (United States)

2011-01-01

Background Clonorchis sinensis is a carcinogenic human liver fluke that is widespread in Asian countries. Increasing infection rates of this neglected tropical disease are leading to negative economic and public health consequences in affected regions. Experimental and epidemiological studies have shown a strong association between the incidence of cholangiocarcinoma and the infection rate of C. sinensis. To aid research into this organism, we have sequenced its genome. Results We combined de novo sequencing with computational techniques to provide new information about the biology of this liver fluke. The assembled genome has a total size of 516 Mb with a scaffold N50 length of 42 kb. Approximately 16,000 reliable protein-coding gene models were predicted. Genes for the complete pathways for glycolysis, the Krebs cycle and fatty acid metabolism were found, but key genes involved in fatty acid biosynthesis are missing from the genome, reflecting the parasitic lifestyle of a liver fluke that receives lipids from the bile of its host. We also identified pathogenic molecules that may contribute to liver fluke-induced hepatobiliary diseases. Large proteins such as multifunctional secreted proteases and tegumental proteins were identified as potential targets for the development of drugs and vaccines. Conclusions This study provides valuable genomic information about the human liver fluke C. sinensis and adds to our knowledge on the biology of the parasite. The draft genome will serve as a platform to develop new strategies for parasite control. PMID:22023798

Comparative Metabolism Study of Five Protoberberine Alkaloids in Liver Microsomes from Rat, Rhesus Monkey, and Human.

Science.gov (United States)

Li, Yan; Zhou, Yanyan; Si, Nan; Han, Lingyu; Ren, Wei; Xin, Shaokun; Wang, Hongjie; Zuo, Ran; Wei, Xiaolu; Yang, Jian; Zhao, Haiyu; Bian, Baolin

2017-11-01

Protoberberine alkaloids including berberine, palmatine, jatrorrhizine, coptisine, and epiberberine are major components in many medicinal plants. They have been widely used for the treatment of cancer, inflammation, diabetes, depression, hypertension, and various infectious areas. However, the metabolism of five protoberberine alkaloids among different species has not been clarified previously. In order to elaborate on the in vitro metabolism of them, a comparative analysis of their metabolic profile in rat, rhesus monkey, and human liver microsomes was carried out using ultrahigh-performance liquid chromatography coupled with a high-resolution linear trap quadrupole-Orbitrap mass spectrometer (UHPLC-electrospray ionization-Orbitrap MS) for the first time. Each metabolite was identified and semiquantified by its accurate mass data and peak area. Fifteen metabolites were characterized based on accurate MS/MS spectra and the proposed MS/MS fragmentation pathways including demethylation, hydroxylation, and methyl reduction. Among them, the content of berberine metabolites in human liver microsomes was similar with those in rhesus monkey liver microsomes, whereas berberine in rat liver microsomes showed no demethylation metabolites and the content of metabolites showed significant differences with that in human liver microsomes. On the contrary, the metabolism of palmatine in rat liver microsomes resembled that in human liver microsomes. The content of jatrorrhizine metabolites presented obvious differences in all species. The HR-ESI-MS/MS fragmentation behavior of protoberberine alkaloids and their metabolic profile in rat, rhesus monkey, and human liver microsomes were investigated for the first time. The results demonstrated that the biotransformation characteristics of protoberberine alkaloids among different species had similarities as well differences that would be beneficial for us to better understand the pharmacological activities of protoberberine alkaloids

MR imaging in pancreas head cancer

International Nuclear Information System (INIS)

Yokota, Hajime; Yamanouchi, Baisetsu; Takarada, Akira; Tonami, Hisao; Okimura, Tetsuro; Miyamura, Toshio; Yamamoto, Itaru; Kinami, Yoshio

1989-01-01

To reduce artifacts associated with MRI, we used abdominal belts and anticholinergic during the examinations in patients with pancreas head cancer. In selected cases, foric pyrophosphate was injected into the common bile duct as a contrast medium. We made a comparative study of the results of MRI with those of CT with regard to lesion detectability and diagnostic ability of tumor invasion. MR examinations were performed at 0.5 Tesla superconducting unit using spin-echo (SE) pulse sequences. Eleven patients with pancreas head cancer were enrolled in this study. As to the lesion detectability, eight cases (73%) were detected clearly or moderately clearly on MRI, almost corresponding to 9 cases (82%) on CT. With regard to the neoplastic infiltration to the surrounding area, MRI and CT were almost equally efficient as to the capsular and the arterial invasion. However, as to the invasion to the posterion surface of pancreas and the portal system, MRI was a little superior to CT. In patients to whom foric pyrophosphate was injected, the choledochal duct was clearly separated from the tumor. In conclusion, our results suggest that MRI using abdominal belts, anticholinergic and foric pyrophosphate solution is extremely effective in the diagnosis of pancreas head cancer and is almost as efficient as CT. (author)

Radionuclide imaging of the liver in human fascioliasis

International Nuclear Information System (INIS)

Rivera, J.V.; Bermudez, R.H.

1984-01-01

The clinical, laboratory, and scintigraphic findings in four cases of human fascioliasis are described. Acute onset of fever, abdominal pain, and weight loss in a person who has ingested watercress constitutes the clinical syndrome often seen. Eosinophilia and alteration in liver function tests, particularly alkaline phosphatase are frequent. Tc-99m sulfur colloid images showed hepatomegaly in four patients, focal defects in two, splenomegaly in three, and increased splenic uptake in two. Gallium citrate (Ga 67) images show increased uptake in the focal lesions in two of two. Sonographic imaging showed focal lucent abnormality in one of three. Liver biopsy findings were nonspecific. The differential diagnosis from other invasive parasitic diseases is discussed. A possible role of hepatic imaging in the evaluation of fascioliasis is suggested

Liver lipase and high-density lipoprotein. Lipoprotein changes after incubation of human serum with rat liver lipase.

Science.gov (United States)

Groot, P H; Scheek, L M; Jansen, H

1983-05-16

Human sera were incubated with rat liver lipase after inactivation of lecithin:cholesterol acyltransferase, and the changes in serum lipoprotein composition were measured. In the presence of liver lipase serum triacylglycerol and phosphatidylcholine were hydrolyzed. The main changes in the concentrations of these lipids were found in the high-density lipoprotein fraction. Subfractionation of high-density lipoprotein by rate-zonal ultracentrifugation showed a prominent decrease in all constituents of high-density lipoprotein2, a smaller decrease in the 'light' high-density lipoprotein3 and an increase in the 'heavy' high-density lipoprotein3. These data support a concept in which liver lipase is involved in high-density lipoprotein2 phospholipid and triacylglycerol catabolism and suggest that as a result of this action high-density lipoprotein2 is converted into high-density lipoprotein3.

Computed tomography and ultrasound of the normal pancreas

International Nuclear Information System (INIS)

Kolmannskog, F.; Swensen, T.; Vatn, M.H.; Larsen, S.

1982-01-01

Computed tomography (CT) and ultrasound (US) were performed on 47 patients with a normal pancreas. CT was a significantly better method than US to demonstrate the pancreatic body and tail. The pancreatic head was also shown more often using CT than US, but this difference was not statistically significant. The diameters of the different parts of the pancreas measured at CT were significantly larger than measured at US. The explanation is most probably that the widths of the splenic and superior mesenteric veins are added to the diameters of the pancreas measured at CT, while using US, these vessels are clearly differentiated from the pancreatic tissue. US was a significantly better technique than CT to register the vascular structures surrounding the pancreas, except from the left renal vein, which was more often demonstrated at CT. (Auth.)

Testosterone biotransformation by the isolated perfused canine pancreas

International Nuclear Information System (INIS)

Fernandez-del Castillo, C.; Diaz-Sanchez, V.; Varela-Fascinetto, G.; Altamirano, A.; Odor-Morales, A.; Lopez-Medrano, R.M.; Robles-Diaz, G.

1991-01-01

There is strong evidence indicating that the pancreas is under the influence of sex steroid hormones, and that it may even participate in their biosynthesis and metabolism. In the present study, [3H]testosterone was perfused into the isolated canine pancreas, and measured in the effluent with several of its metabolites (5 alpha-dihydrotestosterone, androstenedione, and estradiol). Results show that testosterone is readily transformed by the canine pancreas. The main product found in the effluent is androstenedione. The testis and spleen were also perfused with [3H]testosterone and used as controls. In both cases, this hormone appeared mostly unchanged in the effluent as compared to the pancreatic perfusion (p less than 0.0001). From our data, we conclude that the canine pancreas has the capacity to transform sex steroid hormones, and could be considered an extragonadal site of sex steroid biosynthesis

Testosterone biotransformation by the isolated perfused canine pancreas

Energy Technology Data Exchange (ETDEWEB)

Fernandez-del Castillo, C.; Diaz-Sanchez, V.; Varela-Fascinetto, G.; Altamirano, A.; Odor-Morales, A.; Lopez-Medrano, R.M.; Robles-Diaz, G. (Instituto Nacional de la Nutricion Salvador Zubiran, Mexico City (Mexico))

1991-01-01

There is strong evidence indicating that the pancreas is under the influence of sex steroid hormones, and that it may even participate in their biosynthesis and metabolism. In the present study, (3H)testosterone was perfused into the isolated canine pancreas, and measured in the effluent with several of its metabolites (5 alpha-dihydrotestosterone, androstenedione, and estradiol). Results show that testosterone is readily transformed by the canine pancreas. The main product found in the effluent is androstenedione. The testis and spleen were also perfused with (3H)testosterone and used as controls. In both cases, this hormone appeared mostly unchanged in the effluent as compared to the pancreatic perfusion (p less than 0.0001). From our data, we conclude that the canine pancreas has the capacity to transform sex steroid hormones, and could be considered an extragonadal site of sex steroid biosynthesis.

Gatekeepers of pancreas: TEAD and YAP

OpenAIRE

Rodríguez Seguí, Santiago Andrés; Bessa, José

2017-01-01

The pancreas hosts some of the most debilitating and deadly diseases, including pancreatic cancer and diabetes mellitus. In autoimmune diabetes, for example, there is a massive destruction of the insulin producing cells of the pancreas. Pancreatic developmental defects can also result in a deficit of this cell type. To revert these important pancreatic diseases, researchers are currently trying to artificially generate insulin producing beta-cells for implantation and, in this way, suppress i...

Multi-slice CT features of annular pancreas in neonates

International Nuclear Information System (INIS)

He Mingqing; Zhu Youzhi; Hu Kefei; Yin Chuangao; Hu Jun; Wang Song; Li Xu; Lu Zhongbin; Wang Yue; Liu Xiang

2013-01-01

Objective: To investigate the MSCT manifestations and their values in the diagnosis of annular pancreas in neonates. Methods: Retrospective analysis of clinical and CT findings in 27 cases with surgery-proved annular pancreas in neonates was made. The unenhanced and contrast-enhanced CT images were obtained in 20 patients. Two experienced radiologists determined the site and degree of obstruction, the relationship between the head of the pancreas and the obstruction point, and the surrounding tissue structure. Results: The direct signs included the fluid-filled or gas-filled bowel in the head of pancreas in 4 cases, the enhancement of surrounding soft tissue as enhanced pancreas in 17 cases, disappearance of the fat gap between the intestinal wall and the annular pancreas in 17 cases. The indirect signs included intestinal obstruction in 20 cases, 'single-bubble sign' in 2 cases, 'double-bubble sign' in 18 cases, the distal bowel without gas in 5 cases, small amount of gas in the distal bowel in 15 cases. In 12 of 18 cases showing 'double-bubble sign', the ratio of duodenal bubble diameter (Dd) to stomach bubble diameter (Ds)was over 1.0. The site of obstruction was located in the descending duodenum in 20 cases. The form of obstructed point presented with 'nipple sign' in 15 cases, with 'the mouse tail' in 5 cases. The expansion bowel was located in the head of pancreas in 1 case. Gas was found in the pancreatic duct in 1 case, and 'swirl sign' was shown in 2 cases. Conclusions: MSCT combined with three-dimensional reconstruction techniques can clearly demonstrate the annular pancreas' s shape, the site and degree of obstruction and other malformations. It can provide important information for clinical treatment. (authors)

Reconstructed coronal views of CT and isotopic images of the pancreas

International Nuclear Information System (INIS)

Kasuga, Toshio; Kobayashi, Toshio; Nakanishi, Fumiko

1980-01-01

To compare functional images of the pancreas by scintigraphy with morphological views of the pancreas by CT, CT coronal views of the pancreas were reconstructed. As CT coronal views were reconstructed from the routine scanning, there was a problem in longitudinal spatial resolution. However, almost satisfactory total images of the pancreas were obtained by improving images adequately. In 27 patients whose diseases had been confirmed, it was easy to compare pancreatic scintigrams with pancreatic CT images by using reconstructed CT coronal views, and information which had not been obtained by original CT images could be obtained by using reconstructed CT coronal views. Especially, defects on pancreatic images and the shape of pancreas which had not been visualized clearly by scintigraphy alone could be visualized by using reconstructed CT coronal views of the pancreas. (Tsunoda, M.)

Solid and papillary neoplasm of the pancreas

DEFF Research Database (Denmark)

Jørgensen, L J; Hansen, A B; Burcharth, F

1992-01-01

In two cases of solid and papillary neoplasm of the pancreas (SPN), positive staining for argyrophil granules, chromogranin-A, neuron-specific enolase, chymotrypsin, alpha 1-antitrypsin, vimentin, cytokeratin, and estrogen receptors was present. Ultrastructurally, neurosecretory as well as zymoge......In two cases of solid and papillary neoplasm of the pancreas (SPN), positive staining for argyrophil granules, chromogranin-A, neuron-specific enolase, chymotrypsin, alpha 1-antitrypsin, vimentin, cytokeratin, and estrogen receptors was present. Ultrastructurally, neurosecretory as well...... as zymogenlike granules were demonstrated. Measurements of mean nuclear volume and volume-corrected mitotic index discriminated between SPN and well-differentiated ductal adenocarcinoma of the pancreas, with notably lower values being seen in SPN. Silver-stained nucleolar organizer region counts showed wide...

Morphology and some biomechanical properties of human liver and spleen

Czech Academy of Sciences Publication Activity Database

Stingl, J.; Bača, V.; Čech, V.; Kovanda, J.; Kovandová, H.; Mandys, Václav; Rejmontová, J.; Sosna, B.

2002-01-01

Roč. 24, - (2002), s. 285-289 ISSN 0930-1038 Institutional research plan: CEZ:AV0Z5039906 Keywords : Human liver and spleen Subject RIV: FE - Other Internal Medicine Disciplines Impact factor: 0.252, year: 2002

Agenesis of pancreas

DEFF Research Database (Denmark)

Voldsgaard, P; Kryger-Baggesen, N; Lisse, I

1994-01-01

Complete agenesis of pancreas is a rare and lethal condition. Four cases have previously been reported in combination with other malformations, such as severe intrauterine growth retardation, hyperglycaemia and meconium ileus. We report a case of pancreatic agenesis as a single anomaly. The child...

Immunohistochemistry detected and localized cannabinoid receptor type 2 in bovine fetal pancreas at late gestation

Directory of Open Access Journals (Sweden)

Cecilia Dall'Aglio

2017-03-01

Full Text Available At present, data on the endocannabinoid system expression and distribution in the pancreatic gland appear scarce and controversial as descriptions are limited to humans and laboratory animals. Since the bovine pancreas is very similar to the human in endocrine portion development and control, studies on the fetal gland could prove to be very interesting, as an abnormal maternal condition during late pregnancy may be a predisposing trigger for adult metabolic disorders. The present investigation studied cannabinoid receptor type 2 presence and distribution in the bovine fetal pancreas towards the end of gestation. Histological analyses revealed numerous endocrinal cell clusters or islets which were distributed among exocrine adenomeri in connectival tissue. Immunohistochemistry showed that endocrine-islets contained some CB2-positive cells with a very peculiar localization that is a few primarily localized at the edges of islets and some of them also scattered in the center of the cluster. Characteristically, also the epithelium of the excretory ducts and the smooth muscle layers of the smaller arteries, in the interlobular glandular septa, tested positive for the CB2 endocannabinoid receptor. Conse - quently, the endocannabinoid system, via the cannabinoid receptor type 2, was hypothesized to play a major role in controlling pancreas function from normal fetal development to correct metabolic functioning in adulthood.

A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

Energy Technology Data Exchange (ETDEWEB)

Yannam, Govardhana Rao [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Han, Bing [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an, Shaanxi (China); Setoyama, Kentaro [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamamoto, Toshiyuki [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Ito, Ryotaro; Brooks, Jenna M. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Guzman-Lepe, Jorge [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Galambos, Csaba [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Fong, Jason V. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Deutsch, Melvin; Quader, Mubina A. [Department of Radiation Oncology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamanouchi, Kosho [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kabarriti, Rafi; Mehta, Keyur [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Soto-Gutierrez, Alejandro [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); and others

2014-02-01

Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

International Nuclear Information System (INIS)

Yannam, Govardhana Rao; Han, Bing; Setoyama, Kentaro; Yamamoto, Toshiyuki; Ito, Ryotaro; Brooks, Jenna M.; Guzman-Lepe, Jorge; Galambos, Csaba; Fong, Jason V.; Deutsch, Melvin; Quader, Mubina A.; Yamanouchi, Kosho; Kabarriti, Rafi; Mehta, Keyur; Soto-Gutierrez, Alejandro

2014-01-01

Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury

Humanizing π-class glutathione S-transferase regulation in a mouse model alters liver toxicity in response to acetaminophen overdose.

Directory of Open Access Journals (Sweden)

Matthew P Vaughn

Full Text Available Glutathione S-transferases (GSTs metabolize drugs and xenobiotics. Yet despite high protein sequence homology, expression of π-class GSTs, the most abundant of the enzymes, varies significantly between species. In mouse liver, hepatocytes exhibit high mGstp expression, while in human liver, hepatocytes contain little or no hGSTP1 mRNA or hGSTP1 protein. π-class GSTs are known to be critical determinants of liver responses to drugs and toxins: when treated with high doses of acetaminophen, mGstp1/2+/+ mice suffer marked liver damage, while mGstp1/2-/- mice escape liver injury.To more faithfully model the contribution of π-class GSTs to human liver toxicology, we introduced hGSTP1, with its exons, introns, and flanking sequences, into the germline of mice carrying disrupted mGstp genes. In the resultant hGSTP1+mGstp1/2-/- strain, π-class GSTs were regulated differently than in wild-type mice. In the liver, enzyme expression was restricted to bile duct cells, Kupffer cells, macrophages, and endothelial cells, reminiscent of human liver, while in the prostate, enzyme production was limited to basal epithelial cells, reminiscent of human prostate. The human patterns of hGSTP1 transgene regulation were accompanied by human patterns of DNA methylation, with bisulfite genomic sequencing revealing establishment of an unmethylated CpG island sequence encompassing the gene promoter. Unlike wild-type or mGstp1/2-/- mice, when hGSTP1+mGstp1/2-/- mice were overdosed with acetaminophen, liver tissues showed limited centrilobular necrosis, suggesting that π-class GSTs may be critical determinants of toxin-induced hepatocyte injury even when not expressed by hepatocytes.By recapitulating human π-class GST expression, hGSTP1+mGstp1/2-/- mice may better model human drug and xenobiotic toxicology.

Novel circulatory connection from the acupoint Zhong Wan(CV12 to pancreas

Directory of Open Access Journals (Sweden)

Minsoo Kim

2008-03-01

Full Text Available Objectives : Demonstrating a novel circulatory path from the acupoint(CV12 to the pancreas. Method : Alcian blue(1% solution, 20μl, pH 7.4 was injected into the acupoint(CV12. Two hours later the surfaces of internal organs were observed by using a stereomicroscope. Results : Alcian blue arrived and colored the omental fat band(OFB on the pancreas. The OFB connected the head and tail of the pancreas, the pancreas and the spleen, and the pancreas and the stomach. Conclusion : The existence of a novel circulatory path from the acupoint CV12 to the pancreas and its OFB was demonstrated.

Celioscopic liver biopsy in silver catfish (Rhamdia quelen

Directory of Open Access Journals (Sweden)

João P.S. Feranti

2015-01-01

Full Text Available Endosurgery has been used for assessment of fish celomatic cavity, as well as for obtaining biopsies for organic analysis. Such minimally invasive access may also be used for the analysis of environmental impact on biomarkers of pollution. In Brazil, studies and literature regarding the use of celioscopy in fish are sparse. The purpose of the current study was to develop a two-port celioscopy technique to obtain liver biopsy in silver catfish (Rhamdia quelen. Six adult female silver catfish were used. The animals were anesthetized and the inspection of the celomatic cavity were performed using a telescope and celioscopic-guided liver biopsy were taken using laparoscopic Kelly forceps. On the early postoperative period, the animals were released in a confined water reservoir where mortality could be checked. The liver samples were sent for histological assessment. There were no complications during surgery on early postoperative period. It was possible to visualize meticulously several organs (liver, spleen, stomach, pancreas, swim bladder, ovaries, bowel and transverse septum. In conclusion, the surgical technique and the anesthetic protocol proposed were suitable to perform liver biopsies in silver catfish and provided low morbidity.

Three-Dimensional Culture of Human Embryonic Stem Cell Derived Hepatic Endoderm and Its Role in Bioartificial Liver Construction

Directory of Open Access Journals (Sweden)

Ruchi Sharma

2010-01-01

Full Text Available The liver carries out a range of functions essential for bodily homeostasis. The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality. Presently, liver transplantation remains the only effective treatment, but donor availability is a major limitation. Therefore, artificial and bioartificial liver devices have been developed to bridge patients to liver transplantation. Existing support devices improve hepatic encephalopathy to a certain extent; however their usage is associated with side effects. The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes. Moreover, primary hepatocytes are difficult to maintain and lose hepatic identity and function over time even with sophisticated tissue culture media. To overcome this limitation, renewable cell sources are being explored. Human embryonic stem cells are one such cellular resource and have been shown to generate a reliable and reproducible supply of human hepatic endoderm. Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays.

Rat pancreas secretes particulate ecto-nucleotidase CD39

DEFF Research Database (Denmark)

Sørensen, Christiane Elisabeth; Amstrup, Jan; Rasmussen, Hans N

2003-01-01

In exocrine pancreas, acini release ATP and the excurrent ducts express several types of purinergic P2 receptors. Thereby, ATP, or its hydrolytic products, might play a role as a paracrine regulator between acini and ducts. The aim of the present study was to elucidate whether this acinar......-ductal signalling is regulated by nucleotidase(s), and to characterize and localize one of the nucleotidases within the rat pancreas. Using RT-PCR and Western blotting we show that pancreas expresses the full length ecto-nucleoside triphosphate diphosphohydrolase, CD39. Immunofluorescence shows CD39 localization...... relocalizes in clusters towards the lumen and is secreted. As a result, pancreatic juice collected from intact pancreas stimulated with CCK-8 contained nucleotidase activity, including that of CD39, and no detectable amounts of ATP. Anti-CD39 antibodies detected the full length (78 kDa) CD39 in pancreatic...

Metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy LSD (O-H-LSD) in human liver microsomes and cryopreserved human hepatocytes.

Science.gov (United States)

Klette, K L; Anderson, C J; Poch, G K; Nimrod, A C; ElSohly, M A

2000-10-01

The metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) was investigated in liver microsomes and cyropreserved hepatocytes from humans. Previous studies have demonstrated that O-H-LSD is present in human urine at concentrations 16-43 times greater than LSD, the parent compound. Additionally, these studies have determined that O-H-LSD is not generated during the specimen extraction and analytical processes or due to parent compound degradation in aqueous urine samples. However, these studies have not been conclusive in demonstrating that O-H-LSD is uniquely produced during in vivo metabolism. Phase I drug metabolism was investigated by incubating human liver microsomes and cryopreserved human hepatocytes with LSD. The reaction was quenched at various time points, and the aliquots were extracted using liquid partitioning and analyzed by liquid chromatography-mass spectrometry. O-H-LSD was positively identified in all human liver microsomal and human hepatocyte fractions incubated with LSD. In addition, O-H-LSD was not detected in any microsomal or hepatocyte fraction not treated with LSD nor in LSD specimens devoid of microsomes or hepatocytes. This study provides definitive evidence that O-H-LSD is produced as a metabolic product following incubation of human liver microsomes and hepatocytes with LSD.

Lymphoepithelial cyst of the pancreas: a case report

International Nuclear Information System (INIS)

Joo, Seung Ho; Kim, Myeong Jin; Kim, Ki Whang; Park, Young Nyun; Shim, Hyp Sup; Lim, Joon Seok

2005-01-01

We present a case of lymphoepithelial cyst of the pancreas. The cyst showed moderate echogenicity, mimicking a solid lesion on ultrasonography (US), and had a cystic appearance on computed tomography (CT). This ambivalent finding may be a distinctive feature of lymphoepithelial cysts of the pancreas

Extended normothermic extracorporeal perfusion of isolated human liver after warm ischaemia: a preliminary report.

Science.gov (United States)

Bellomo, Rinaldo; Marino, Bruno; Starkey, Graeme; Fink, Michael; Wang, Bao Zhong; Eastwood, Glenn M; Peck, Leah; Young, Helen; Houston, Shane; Skene, Alison; Opdam, Helen; Jones, Robert

2014-09-01

Donation after circulatory death (DCD) livers are at markedly increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to transplant DCD livers and may allow their use for artificial extracorporeal liver support of patients with fulminant liver failure. We conducted two proof-of-concept experiments using human livers after DCD to assess the feasibility and functional efficacy of NELP over an extended period. We applied extracorporeal membrane oxygenation, parenteral nutrition, separate hepatic artery and portal vein perfusion and physiological perfusion pressures to two livers obtained after DCD. We achieved NELP and evidence of liver function (bile production, paracetamol removal and maintenance of normal lactate levels) in both livers; one for 24 hours and the other for 43 hours. Histological examination showed areas of patchy ischaemia but preserved biliary ducts and canaliculi. Our experiments justify further investigations of the feasibility and efficacy of extended DCD liver preservation by ex-vivo perfusion.

Common hepatic artery aneurysm: Pseudopseudocyst of the pancreas

International Nuclear Information System (INIS)

Shultz, S.; Druy, E.M.; Friedman, A.C.

1985-01-01

The preoperative diagnosis of hepatic artery aneurysm is uncommon, and its presentation as a pancreatic mass is rare. Because of its great potential for rupture early diagnosis and treatment is essential. The authors report two cases of aneurysms of the common hepatic artery, which on CT presented as a cystic mass in the head of the pancreas. These cases illustrate the importance of using 10-mm serial sections through the pancreas after a bolus injection of intravenous contrast material in order to allow distinction between hepatic artery aneurysm and other, more common, cystic masses of the pancreas

Endoscopic ultrasound-guided radiofrequency ablation of the pancreas

DEFF Research Database (Denmark)

Silviu, Ungureanu Bogdan; Daniel, Pirici; Claudiu, Mărgăritescu

2015-01-01

ultrasound (EUS)-guided radiofrequency ablation (RFA) probe through a 19G needle in order to achieve a desirable necrosis area in the pancreas. Radiofrequency ablation of the head of the pancreas was performed on 10 Yorkshire pigs with a weight between 25 kg and 35 kg and a length of 40-70 cm. Using an EUS...... analysis revealed increased values of amylase, alkaline phosphatase, and gamma-glutamyl transpeptidase on the 3rd day but a decrease on the 5th day. After necropsy and isolation of the pancreas, the ablated area was easily found, describing a solid necrosis. The pathological examination revealed...

Diagnosis and surgical therapy of pancreas tumors

International Nuclear Information System (INIS)

Heid, A.

1981-01-01

The efficiency of surgery and presurgical diagnosis on several tumorous diseases of the pancreas is investigated. If there is the clinical suspicion of a pancreas carcinoma, sonography computerized tomography, and endoscopic-retrograde cholangio-pancreaticography (ERCP) bring the best diagnostic results. In case of pancreatogenic hyperinsulinism a selective angiography should be carried out in any case for an exact presurgical localisation. (orig./MG) [de

Endocrine pancreas development at weaning in goat kids

Directory of Open Access Journals (Sweden)

Fabia Rosi

2010-01-01

Full Text Available Eighteen three-day old Saanen goat kids were divided into MILK and WEAN groups. MILK kids received goat milk to age 48 days; WEAN kids were initially fed milk but started weaning at 25 days and were completely weaned by 40 days. Total intake per group was recorded daily. On day 25, 40 and 48, body weights were recorded, and plasma samples were taken and analyzed for glucose, free amino-acids and insulin. On day 48, all animals were slaughtered and pancreas samples were analyzed for total DNA and RNA content. Histological sections of pancreas were examined by light microscope and images analyzed by dedicated software. Seven days after the beginning of the weaning program, dry matter intake in the WEAN group began to decrease compared to the MILK one. Nonetheless, body weight did not differ throughout the study period. Weaning significantly decreased plasma levels of glucose, amino-acids and insulin. No difference was observed in pancreatic DNA and RNA content. Histological analysis of pancreas showed that the size of pancreatic islets was not different, but islet number per section was lower in the pancreas of WEAN animals. In conclusion, weaning affects glucose and amino-acid metabolism and influences endocrine pancreas activity and morphology.

Spatiotemporal proteomic analyses during pancreas cancer progression identifies serine/threonine stress kinase 4 (STK4) as a novel candidate biomarker for early stage disease.

Science.gov (United States)

Mirus, Justin E; Zhang, Yuzheng; Hollingsworth, Michael A; Solan, Joell L; Lampe, Paul D; Hingorani, Sunil R

2014-12-01

Pancreas cancer, or pancreatic ductal adenocarcinoma, is the deadliest of solid tumors, with a five-year survival rate of pancreas cancer. Mouse models that accurately recapitulate the human condition allow disease tracking from inception to invasion and can therefore be useful for studying early disease stages in which surgical resection is possible. Using a highly faithful mouse model of pancreas cancer in conjunction with a high-density antibody microarray containing ∼2500 antibodies, we interrogated the pancreatic tissue proteome at preinvasive and invasive stages of disease. The goal was to discover early stage tissue markers of pancreas cancer and follow them through histologically defined stages of disease using cohorts of mice lacking overt clinical signs and symptoms and those with end-stage metastatic disease, respectively. A panel of seven up-regulated proteins distinguishing pancreas cancer from normal pancreas was validated, and their levels were assessed in tissues collected at preinvasive, early invasive, and moribund stages of disease. Six of the seven markers also differentiated pancreas cancer from an experimental model of chronic pancreatitis. The levels of serine/threonine stress kinase 4 (STK4) increased between preinvasive and invasive stages, suggesting its potential as a tissue biomarker, and perhaps its involvement in progression from precursor pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma. Immunohistochemistry of STK4 at different stages of disease revealed a dynamic expression pattern further implicating it in early tumorigenic events. Immunohistochemistry of a panel of human pancreas cancers confirmed that STK4 levels were increased in tumor epithelia relative to normal tissue. Overall, this integrated approach yielded several tissue markers that could serve as signatures of disease stage, including early (resectable), and therefore clinically meaningful, stages. © 2014 by The American Society for

Radical antegrade modular pancreatosplenectomy for adenocarcinomaof the body of the pancreas in a patient with portal annular pancreas, aberrant hepatic artery, and absence of the celiac trunk: A case report.

Science.gov (United States)

Yuan, Hao; Wu, Pengfei; Chen, Jianmin; Lu, Zipeng; Chen, Lei; Wei, Jishu; Guo, Feng; Cai, Baobao; Yin, Jie; Xu, Dong; Jiang, Kuirong; Miao, Yi

2017-12-01

Portal annular pancreas is a rare anatomic variation, where the uncinated process of the pancreas connects with the dorsal pancreas and the pancreas tissue encases the portal vein (PV), superior mesenteric vein (SMV) or splenic vein (SV). Malignancies are quite uncommon in the patients, who have an annular pancreas especially portal annular pancreas. Ectopic common hepatic artery and absence of the celiac trunk (CT) are the other infrequent abnormalities. A 74-year-old man suffered from upper abdominal and back pain. Contrast enhanced computed tomography indicated a low-density mass in the body of the pancreas. Pathological report showed adenocarcinoma of the body of pancreas after radical antegrade modular pancreatosplenectomy (RAMPS). In the operation, we found the superior vein and portal vein was surrounded by the pancreatic tissue. The left gastric artery and splenic artery originated respectively from abdominal aorta, and celiac trunk was not viewed. In addition, the common hepatic artery was a branch from the superior mesenteric artery. In general, this is a novel clinical case of pancreatic carcinoma happening in the portal annular pancreas which was accompanied with aberrant hepatic artery and absence of the celiac trunk at the same time. Confronted with the pancreatic neoplasms, the possibility of coexistent annular pancreas and arterial variations should be considered.

Elastography for the pancreas: Current status and future perspective.

Science.gov (United States)

Kawada, Natsuko; Tanaka, Sachiko

2016-04-14

Elastography for the pancreas can be performed by either ultrasound or endoscopic ultrasound (EUS). There are two types of pancreatic elastographies based on different principles, which are strain elastography and shear wave elastography. The stiffness of tissue is estimated by measuring the grade of strain generated by external pressure in the former, whereas it is estimated by measuring propagation speed of shear wave, the transverse wave, generated by acoustic radiation impulse (ARFI) in the latter. Strain elastography is difficult to perform when the probe, the pancreas and the aorta are not located in line. Accordingly, a fine elastogram can be easily obtained in the pancreatic body but not in the pancreatic head and tail. In contrast, shear wave elastography can be easily performed in the entire pancreas because ARFI can be emitted to wherever desired. However, shear wave elastography cannot be performed by EUS to date. Recently, clinical guidelines for elastography specialized in the pancreas were published from Japanese Society of Medical Ultrasonics. The guidelines show us technical knacks of performing elastography for the pancreas.

Elastography for the pancreas: Current status and future perspective

Science.gov (United States)

Kawada, Natsuko; Tanaka, Sachiko

2016-01-01

Elastography for the pancreas can be performed by either ultrasound or endoscopic ultrasound (EUS). There are two types of pancreatic elastographies based on different principles, which are strain elastography and shear wave elastography. The stiffness of tissue is estimated by measuring the grade of strain generated by external pressure in the former, whereas it is estimated by measuring propagation speed of shear wave, the transverse wave, generated by acoustic radiation impulse (ARFI) in the latter. Strain elastography is difficult to perform when the probe, the pancreas and the aorta are not located in line. Accordingly, a fine elastogram can be easily obtained in the pancreatic body but not in the pancreatic head and tail. In contrast, shear wave elastography can be easily performed in the entire pancreas because ARFI can be emitted to wherever desired. However, shear wave elastography cannot be performed by EUS to date. Recently, clinical guidelines for elastography specialized in the pancreas were published from Japanese Society of Medical Ultrasonics. The guidelines show us technical knacks of performing elastography for the pancreas. PMID:27076756

Purinergic signalling in the pancreas in health and disease

DEFF Research Database (Denmark)

Burnstock, G; Novak, I

2012-01-01

Pancreatic cells contain specialised stores for ATP. Purinergic receptors (P2 and P1) and ecto-nucleotidases are expressed in both endocrine and exocrine calls, as well as in stromal cells. The pancreas, especially the endocrine cells, were an early target for the actions of ATP. After the histor......Pancreatic cells contain specialised stores for ATP. Purinergic receptors (P2 and P1) and ecto-nucleotidases are expressed in both endocrine and exocrine calls, as well as in stromal cells. The pancreas, especially the endocrine cells, were an early target for the actions of ATP. After...... the historical perspective of purinergic signalling in the pancreas, the focus of this review will be the physiological functions of purinergic signalling in the regulation of both endocrine and exocrine pancreas. Next, we will consider possible interaction between purinergic signalling and other regulatory...... systems and their relation to nutrient homeostasis and cell survival. The pancreas is an organ exhibiting several serious diseases - cystic fibrosis, pancreatitis, pancreatic cancer and diabetes - and some are associated with changes in life-style and are increasing in incidence. There is upcoming...

Exenatide Induces Impairment of Autophagy Flux to Damage Rat Pancreas.

Science.gov (United States)

Li, Zhiqiang; Huang, Lihua; Yu, Xiao; Yu, Can; Zhu, Hongwei; Li, Xia; Han, Duo; Huang, Hui

2017-01-01

The study aimed to explore the alteration of autophagy in rat pancreas treated with exenatide. Normal Sprague-Dawley rats and diabetes-model rats induced by 2-month high-sugar and high-fat diet and streptozotocin injection were subcutaneously injected with exenatide, respectively, for 10 weeks, with homologous rats treated with saline as control. Meanwhile, AR42J cells, pancreatic acinar cell line, were cultured with exenatide at doses of 5 pM for 3 days. The pancreas was disposed, and several sections were stained with hematoxylin-eosin. Immunohistochemistry was used to measure the expressions of glucagon-like peptide 1 receptor (GLP-1R) and cysteine-aspartic acid protease-3 in rat pancreas, and Western blot was used to test the expressions of GLP-1R, light chain 3B-I and -II, and p62 in rat pancreas and AR42J cells. The data were expressed as mean (standard deviation) and analyzed by unpaired Student's t-test. Exenatide can induce pathological changes in rat pancreas. The GLP-1R, p62, light chain 3B-II, and cysteine-aspartic acid protease-3 in rat pancreas and AR42J cells treated with exenatide were significantly overexpressed. Exenatide can activate and upregulate its receptor, GLP-1R, then impair autophagy flux and activate apoptosis in the pancreatic acinar cell, thus damaging rat pancreas.

Pentose pathway in human liver

International Nuclear Information System (INIS)

Magnusson, I.; Chandramouli, V.; Schumann, W.C.; Kumaran, K.; Wahren, J.; Landau, B.R.

1988-01-01

[1- 14 C]Ribose and [1- 14 C]glucose were given to normal subjects along with glucose loads (1 g per kg of body weight) after administration of diflunisal and acetaminophen, drugs that are excreted in urine as glucuronides. Distributions of 14 C were determined in the carbons of the excreted glucoronides and in the glucose from blood samples drawn from hepatic veins before and after glucagon administration. Eighty percent or more of the 14 C from [1- 14 C]ribose incorporated into the glucuronic acid moiety of the glucuronides was in carbons 1 and 3, with less than 8% in carbon 2. In glucuronic acid from glucuronide excreted when [2- 14 C]glucose was given, 3.5-8.1% of the 14 C was in carbon 1, 2.5-4.3% in carbon 3, and more than 70% in carbon 2. These distributions are in accord with the glucuronides sampling the glucose unit of the glucose 6-phosphate pool that is a component of the pentose pathway and is intermediate in glycogen formation. It is concluded that the glucuronic acid conjugates of the drugs can serve as a noninvasive means of sampling hepatic glucose 6-phosphate. In human liver, as in animal liver, the classical pentose pathway functions, not the L-type pathway, and only a small percentage of the glucose is metabolized via the pathway

Use of bipolar radiofrequency in parenchymal transection of the liver, pancreas and kidney.

Science.gov (United States)

Pai, Madhava; Spalding, Duncan; Jiao, Long; Habib, Nagy

2012-01-01

Intraoperative blood loss has been shown to be an important factor correlating with increased morbidity and mortality in oncological surgery. Despite technological advances in parenchymal transection devices, bleeding remains the single most important complication. To address this, we designed and developed a bipolar radiofrequency (RF) device, the Habib 4X (Angiodynamics, Inc., Queensbury, N.Y., USA), which was initially used specifically for liver resections. A search using Medline, Embase and Google™ Scholar was performed for the period January 2001 to August 2011. The following Mesh terms were used: 'bipolar radiofrequency', 'Habib 4X', 'laparoscopic', 'liver resection', 'partial nephrectomy' and 'distal pancreatectomy'. The references of the studies included were also reviewed. Series from our centre were excluded. There were seven series published, reporting a total of 188 liver resections [113 minor (Habib 4X) device over this period. The median blood loss reported ranged from 15 to 427 ml with a transfusion rate of 0-14% In addition, five series of partial nephrectomies were also identified, reporting a total of 149 (45 open and 104 laparoscopic) cases. Hilar clamping was not used in any of the cases, and the mean blood loss reported was 100-337 ml whilst the transfusion rate ranged from 0 to 7.1%. There was only one published series of distal pancreatectomies; these were laparoscopic and included 14 patients. This review of bipolar RF-assisted liver resections, partial nephrectomies and distal pancreatectomies reported in the literature to date shows that there are significant advantages in using this device in these types of operation. Copyright © 2012 S. Karger AG, Basel.

Therapeutic efficacy of human hepatocyte transplantation in a SCID/uPA mouse model with inducible liver disease.

Directory of Open Access Journals (Sweden)

Donna N Douglas

2010-02-01

Full Text Available Severe Combined Immune Deficient (SCID/Urokinase-type Plasminogen Activator (uPA mice undergo liver failure and are useful hosts for the propagation of transplanted human hepatocytes (HH which must compete with recipient-derived hepatocytes for replacement of the diseased liver parenchyma. While partial replacement by HH has proven useful for studies with Hepatitis C virus, complete replacement of SCID/uPA mouse liver by HH has never been achieved and limits the broader application of these mice for other areas of biomedical research. The herpes simplex virus type-1 thymidine kinase (HSVtk/ganciclovir (GCV system is a powerful tool for cell-specific ablation in transgenic animals. The aim of this study was to selectively eliminate murine-derived parenchymal liver cells from humanized SCID/uPA mouse liver in order to achieve mice with completely humanized liver parenchyma. Thus, we reproduced the HSVtk (vTK/GCV system of hepatic failure in SCID/uPA mice.In vitro experiments demonstrated efficient killing of vTK expressing hepatoma cells after GCV treatment. For in vivo experiments, expression of vTK was targeted to the livers of FVB/N and SCID/uPA mice. Hepatic sensitivity to GCV was first established in FVB/N mice since these mice do not undergo liver failure inherent to SCID/uPA mice. Hepatic vTK expression was found to be an integral component of GCV-induced pathologic and biochemical alterations and caused death due to liver dysfunction in vTK transgenic FVB/N and non-transplanted SCID/uPA mice. In SCID/uPA mice with humanized liver, vTK/GCV caused death despite extensive replacement of the mouse liver parenchyma with HH (ranging from 32-87%. Surprisingly, vTK/GCV-dependent apoptosis and mitochondrial aberrations were also localized to bystander vTK-negative HH.Extensive replacement of mouse liver parenchyma by HH does not provide a secure therapeutic advantage against vTK/GCV-induced cytotoxicity targeted to residual mouse hepatocytes

Cystic lesion of pancreas - Intraductal papillary mucinous neoplasm

Directory of Open Access Journals (Sweden)

Rajiv Baijal

2013-01-01

Full Text Available Intraductal papillary mucinous neoplasm (IPMN of the pancreas is an intraductal mucin-producing epithelial neoplasm that arises from the main and/or branched pancreatic duct. It usually presents as cystic lesion of pancreas. There are well known differential diagnosis of cystic pancreatic lesion. Pancreatic cystic neoplasms are detected at an increasing frequency due to an increased use of abdominal imaging. The diagnosis and treatment of intraductal papillary mucinous tumors (IPMN of the pancreas has evolved over the past decade. IPMN represents a spectrum of disease, ranging from benign to malignant lesions, making the early detection and characterization of these lesions important. Definitive management is surgical resection for appropriate candidates, as benign lesions harbor malignant potential. IPMN has a prognosis, which is different from adenocarcinoma of the pancreas. We report a case of a 58-year-old male with intraductal papillary neoplasm involving main duct and side branches presenting to us with clinical symptoms of chronic pancreatitis with obstructive jaundice and cholangitis treated surgically.

Stochastic Differential Equations in Artificial Pancreas Modelling

DEFF Research Database (Denmark)

Duun-Henriksen, Anne Katrine

Type 1 diabetes accounts for approximately 5% of the total diabetes population. It is caused by the destruction of insulin producing β-cells in the pancreas. Various treatment strategies are available today, some of which include advanced technological devices such as an insulin pump and a contin......Type 1 diabetes accounts for approximately 5% of the total diabetes population. It is caused by the destruction of insulin producing β-cells in the pancreas. Various treatment strategies are available today, some of which include advanced technological devices such as an insulin pump...... of the insulin pump and the CGM has paved the way for a fully automatic treatment regime, the artificial pancreas. The idea is to connect the CGM with the insulin pump via a control algorithm running on e.g. the patients smart phone. The CGM observations are sent to the smart phone and based on this information...... of the system directly. The purpose of this PhD-project was to investigate the potential of SDEs in the artificial pancreas development. Especially, the emerging continuous monitoring of glucose levels makes SDEs highly applicable to this field. The current thesis aims at demonstrating and discussing...

Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

NARCIS (Netherlands)

Geuken, Erwin; Visser, Dorien; Kuipers, Folkert; Blokzijl, Hans; Leuvenink, Henri G. D.; de Jong, Koert P.; Peeters, Paul M. J. G.; Jansen, Peter L. M.; Slooff, Maarten J. H.; Gouw, Annette S. H.; Porte, Robert J.

2004-01-01

BACKGROUND/AIMS: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. METHODS: In 28 liver transplant recipients, bile samples were collected daily

Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

NARCIS (Netherlands)

Geuken, E; Visser, D; Kuipers, F; Blokzijl, H; Leuvenink, HGD; de Jong, KP; Peeters, PMJG; Jansen, PLM; Slooff, MJH; Gouw, ASH; Porte, RJ

2004-01-01

Background/Aims: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. Methods: In 28 liver transplant recipients, bile samples were collected daily

Congenital anomalies, hereditary diseases of the pancreas, acute and chronic pancreatitis

International Nuclear Information System (INIS)

Brambs, Hans-Juergen; Juchems, Markus

2011-01-01

The most important congenital anomalies include pancreas divisum, annular pancreas and ectopic pancreas. Patients with pancreas divisum may be more susceptible to acute or chronic pancreatitis and patients with an annular pancreas may develop duodenal stenosis. In pancreas divisum the key finding is the visualization of the main duct draining into the duodenum via the small papilla, separated from the common bile duct. Annular pancreas may show as a well defined ring of pancreatic tissue that encircles the duodenum. Ectopic pancreas is usually asymptomatic but may give rise to abdominal complaints and may be confused with submucosal tumors. Acute pancreatitis is classified as mild or severe. In mild forms ultrasound is the imaging modality of choice whereas in severe forms with extensive pancreatic and peripancreatic necroses computed tomography is the favored method. It is crucial to identify signs and criteria that come along with an increased risk of infection of the necroses. MRI plays an inferior role in the assessment of acute pancreatitis. Chronic pancreatitis is a longstanding inflammatory and fibrosing process causing pain and loss of function. Cross-section imaging is particularly in demand for the detection of complications and the differentiation from pancreatic cancer. Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by lymphoplasmacytic infiltration and fibrosis, and favourable response to corticosteroid treatment. (orig.)

PPARγ regulates exocrine pancreas lipase.

Science.gov (United States)

Danino, Hila; Naor, Ronny Peri-; Fogel, Chen; Ben-Harosh, Yael; Kadir, Rotem; Salem, Hagit; Birk, Ruth

2016-12-01

Pancreatic lipase (triacylglycerol lipase EC 3.1.1.3) is an essential enzyme in hydrolysis of dietary fat. Dietary fat, especially polyunsaturated fatty acids (PUFA), regulate pancreatic lipase (PNLIP); however, the molecular mechanism underlying this regulation is mostly unknown. As PUFA are known to regulate expression of proliferator-activated receptor gamma (PPARγ), and as we identified in-silico putative PPARγ binding sites within the putative PNLIP promoter sequence, we hypothesized that PUFA regulation of PNLIP might be mediated by PPARγ. We used in silico bioinformatics tools, reporter luciferase assay, PPARγ agonists and antagonists, PPARγ overexpression in exocrine pancreas AR42J and primary cells to study PPARγ regulation of PNLIP. Using in silico bioinformatics tools we mapped PPARγ binding sites (PPRE) to the putative promoter region of PNLIP. Reporter luciferase assay in AR42J rat exocrine pancreas acinar cells transfected with various constructs of the putative PNLIP promoter showed that PNLIP transcription is significantly enhanced by PPARγ dose-dependently, reaching maximal levels with multi PPRE sites. This effect was significantly augmented in the presence of PPARγ agonists and reduced by PPARγ antagonists or mutagenesis abrogating PPRE sites. Over-expression of PPARγ significantly elevated PNLIP transcript and protein levels in AR42J cells and in primary pancreas cells. Moreover, PNLIP expression was up-regulated by PPARγ agonists (pioglitazone and 15dPGJ2) and significantly down-regulated by PPARγ antagonists in non-transfected rat exocrine pancreas AR42J cell line cells. PPARγ transcriptionally regulates PNLIP gene expression. This transcript regulation resolves part of the missing link between dietary PUFA direct regulation of PNLIP. Copyright © 2016 Elsevier B.V. All rights reserved.

Physiology of fish endocrine pancreas.

Science.gov (United States)

Plisetskaya, E M

1989-06-01

From the very beginning of physiological studies on the endocine pancreas, fish have been used as experimental subjects. Fish insulin was one of the first vertebrate insulins isolated and one of the first insulins whose primary and then tertiary structures were reported. Before a second pancreatic hormone, glucagon, was characterized, a physiologically active 'impurity', similar to that in mammalian insulin preparations, was found in fish insulins.Fish have become the most widely used model for studies of biosynthesis and processing of the pancreatic hormones. It seems inconceivable, therefore, that until the recent past cod and tuna insulins have been the only purified piscine islet hormones available for physiological experiments. The situation has changed remarkably during the last decade.In this review the contemporary status of physiological studies on the fish pancreas is outlined with an emphasis on the following topics: 1) contents of pancreatic peptides in plasma and in islet tissue; 2) actions of piscine pancreatic hormones in fish; 3) specific metabolic consequences of an acute insufficiency of pancreatic peptides; 4) functional interrelations among pancreatic peptides which differ from those of mammals. The pitfalls, lacunae and the perspectives of contemporary physiological studies on fish endocrine pancreas are outlined.

Intraoperative radiotherapy for cancer of the pancreas

International Nuclear Information System (INIS)

Manabe, Tadao; Nagai, Toshihiro; Tobe, Takayoshi; Shibamoto, Yuta; Takahashi, Masaharu; Abe, Mitsuyuki

1985-01-01

Seven patients treated by intraoperative radiotherapy for cancer of the pancreas were evaluated. Three patients undergoing pancreaticoduodenectomy for cancer of the head of the pancreas received a dose of 2,500--3,000 rad (6--10 MeV Betatron) intraoperatively with or without external beam irradiation at a dose of 2,520 rad (10 MeV lineac X-ray). One patient developed radiation pancreatitis and died 0.8 month after surgery. Autopsy revealed the degeneration of cancer cells in the involved superior mesenteric artery. One died of hepatic metastasis 8.5 months after surgery, however, recurrence was not found in the irradiation field. The other patient who had external beam irradiation combined with intraoperative radiotherapy is alive 7.5 months after surgery. Four patients with unresectable cancer of the body of the pancreas received a dose of 2,500--3,000 rad (13--18 MeV Betatron) intraoperatively with or without external beam irradiation at a dose of 1,500--5,520 rad (10 MeV lineac X-ray). One patient died of peritonitis carcinomatosa 3.0 months after surgery. One patient died of DIC 0.6 month after surgery. Two patients are alive 1.0 and 6.5 months after surgery. In these patients with intraoperative radiotherapy for unresectable cancer of the pancreas, remarkable effects on relief of pain and shrinkage of tumor were obtained. Further pursuit of intraoperative and external beam radiotherapies in combination with pancreatectomy should be indicated in an attempt to prolong survival of patient with cancer of the pancreas. (author)

Disorders of the pediatric pancreas: imaging features

International Nuclear Information System (INIS)

Nijs, Els; Callahan, Michael J.; Taylor, George A.

2005-01-01

The purpose of this manuscript is to provide an overview of the normal development of the pancreas as well as pancreatic pathology in children. Diagnostic imaging plays a major role in the evaluation of the pancreas in infants and children. Familiarity with the range of normal appearance and the diseases that commonly affect this gland is important for the accurate and timely diagnosis of pancreatic disorders in the pediatric population. Normal embryology is discussed, as are the most common congenital anomalies that occur as a result of aberrant development during embryology. These include pancreas divisum, annular pancreas, agenesis of the dorsal pancreatic anlagen and ectopic pancreatic tissue. Syndromes that can manifest pancreatic pathology include: Beckwith Wiedemann syndrome, von Hippel-Lindau disease and autosomal dominant polycystic kidney disease. Children and adults with cystic fibrosis and Shwachman-Diamond syndrome frequently present with pancreatic insufficiency. Trauma is the most common cause of pancreatitis in children. In younger children, unexplained pancreatic injury must always alert the radiologist to potential child abuse. Pancreatic pseudocysts are a complication of trauma, but can also be seen in the setting of acute or chronic pancreatitis from other causes. Primary pancreatic neoplasms are rare in children and are divided into exocrine tumors such as pancreatoblastoma and adenocarcinoma and into endocrine or islet cell tumors. Islet cell tumors are classified as functioning (insulinoma, gastrinoma, VIPoma and glucagonoma) and nonfunctioning tumors. Solid-cystic papillary tumor is probably the most common pancreatic tumor in Asian children. Although quite rare, secondary tumors of the pancreas can be associated with certain primary malignancies. (orig.)

Disorders of the pediatric pancreas: imaging features

Energy Technology Data Exchange (ETDEWEB)

Nijs, Els [University Hospital Gasthuisberg, Department of Radiology, Leuven (Belgium); Callahan, Michael J.; Taylor, George A. [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States)

2005-04-01

The purpose of this manuscript is to provide an overview of the normal development of the pancreas as well as pancreatic pathology in children. Diagnostic imaging plays a major role in the evaluation of the pancreas in infants and children. Familiarity with the range of normal appearance and the diseases that commonly affect this gland is important for the accurate and timely diagnosis of pancreatic disorders in the pediatric population. Normal embryology is discussed, as are the most common congenital anomalies that occur as a result of aberrant development during embryology. These include pancreas divisum, annular pancreas, agenesis of the dorsal pancreatic anlagen and ectopic pancreatic tissue. Syndromes that can manifest pancreatic pathology include: Beckwith Wiedemann syndrome, von Hippel-Lindau disease and autosomal dominant polycystic kidney disease. Children and adults with cystic fibrosis and Shwachman-Diamond syndrome frequently present with pancreatic insufficiency. Trauma is the most common cause of pancreatitis in children. In younger children, unexplained pancreatic injury must always alert the radiologist to potential child abuse. Pancreatic pseudocysts are a complication of trauma, but can also be seen in the setting of acute or chronic pancreatitis from other causes. Primary pancreatic neoplasms are rare in children and are divided into exocrine tumors such as pancreatoblastoma and adenocarcinoma and into endocrine or islet cell tumors. Islet cell tumors are classified as functioning (insulinoma, gastrinoma, VIPoma and glucagonoma) and nonfunctioning tumors. Solid-cystic papillary tumor is probably the most common pancreatic tumor in Asian children. Although quite rare, secondary tumors of the pancreas can be associated with certain primary malignancies. (orig.)

In vivo time-harmonic multifrequency elastography of the human liver

International Nuclear Information System (INIS)

Tzschätzsch, Heiko; Guo, Jing; Streitberger, Kaspar-Josche; Fischer, Thomas; Sack, Ingolf; Ipek-Ugay, Selcan; Braun, Jürgen; Gentz, Enno; Klaua, Robert; Schultz, Michael

2014-01-01

Elastography is capable of noninvasively detecting hepatic fibrosis by imposing mechanical stress and measuring the viscoelastic response in the liver. Magnetic resonance elastography (MRE) relies on time-harmonic vibrations, while most dynamic ultrasound elastography methods employ transient stimulation methods. This study attempts to benefit from the advantages of time-harmonic tissue stimulation, i.e. relative insensitivity to obesity and ascites and mechanical approachability of the entire liver, and the advantages of ultrasound, i.e. time efficiency, low costs, and wide availability, by introducing in vivo time-harmonic elastography (THE) of the human liver using ultrasound and a broad range of harmonic stimulation frequencies. THE employs continuous harmonic shear vibrations at 7 frequencies from 30 to 60 Hz in a single examination and determines the elasticity and the viscosity of the liver from the dispersion of the shear wave speed within the applied frequency range. The feasibility of the method is demonstrated in the livers of eight healthy volunteers and a patient with cirrhosis. Multifrequency MRE at the same drive frequencies was used as elastographic reference method. Similar values of shear modulus and shear viscosity according the Kelvin–Voigt model were obtained by MRE and THE, indicating that the new method is suitable for in vivo quantification of the shear viscoelastic properties of the liver, however, in real-time and at a fraction of the costs of MRE. In conclusion, THE may provide a useful tool for fast assessment of the viscoelastic properties of the liver at low costs and without limitations in obesity, ascites or hemochromatosis. (paper)

Metabolism of styrene in the human liver in vitro: interindividual variation and enantioselectivity

NARCIS (Netherlands)

Wenker, M. A.; Kezić, S.; Monster, A. C.; de Wolff, F. A.

2001-01-01

1. The interindividual variation and enantioselectivity of the in vitro styrene oxidation by cytochrome P450 have been investigated in 20 human microsomal liver samples. Liver samples were genotyped for the CYP2E1*6 and CYP2E1*5B alleles. 2. Kinetic analysis indicated the presence of at least two

The economics of pancreas surgery.

Science.gov (United States)

Vollmer, Charles M

2013-06-01

Pancreas surgery is a paradigm for high-acuity surgical specialization. Given the current intrigue over containing health care expenditures, pancreas surgery provides an ideal model to investigate the cost of care. This article explores the economics of this field from literature accrued over the last 2 decades. The cost of performing a pancreatic resection is established and then embellished with a discussion of the effects of clinical care paths. Then the influence of complications on costs is explored. Next, cost is investigated as an emerging outcome metric regarding variations in pancreatic surgical care. Finally, the societal-level fiscal impact is considered. Copyright © 2013 Elsevier Inc. All rights reserved.

THE REDUCED CANINE PANCREAS TO STUDY THE EFFECTS OF INTRAOPERATIVE RADIOTHERAPY

NARCIS (Netherlands)

HEIJMANS, HJ; MEHTA, D; KLEIBEUKER, JH; SLUITER, WJ; HOEKSTRA, HJ

1993-01-01

A canine model is described to study the tolerance of the pancreas to intra-operative radiotherapy (IORT). The canine pancreas is a horseshoe-shaped organ. To create a homogeneous delivery of IORT to the whole pancreas surgical manipulation is necessary which may induce pancreatitis. A resection of

Trefoil factors are expressed in human and rat endocrine pancreas: differential regulation by growth hormone

DEFF Research Database (Denmark)

Jackerott, Malene; Lee, Ying C; Møllgård, Kjeld

2006-01-01

Trefoil factors (TFFs) 1, 2, and 3 are expressed in mucosal epithelia. TFFs are particular abundant in the intestine in which they play a crucial role in maintenance and restitution of the epithelium. Because pancreas developmentally arises from the primitive foregut, we explored the expression o...

CLINICAL AND FUNCTIONAL FEATURES OF PANCREAS STATE IN RHEUMATOID ARTHRITIS

Directory of Open Access Journals (Sweden)

O. O. Basieva

2000-01-01

Full Text Available Aim of study: complex pancreas study in rheumatoid arthritis (RA. Material and methods: 120 RA pts were examined clinically Pancreas US-and biochemical study (level of a-amylase and lipase of blood serum by kinetic-calorimetric method was performed in this grouh. Results: 50.8% of pts demonstrated increase of pancreas echo, in 23.3%- widened Wirsung s duct, in 45%- single small focal indurations, more often in the body and cauda pancreatis. Decrease of lipolitic and amylolytic pancreas activity is characteristic for RA, especially in systemic process and long-term disease. Clinical and functional disturbances are connected with morphological changes.

Potential genotoxic and cytotoxicity of emamectin benzoate in human normal liver cells.

Science.gov (United States)

Zhang, Zhijie; Zhao, Xinyu; Qin, Xiaosong

2017-10-10

Pesticide residue inducing cancer-related health problems draw people more attention recently. Emamectin benzoate (EMB) has been widely used in agriculture around the world based on its specificity targets. Although potential risk and the molecular mechanism of EMB toxicity to human liver has not been well-characterized. Unlike well-reported toxicity upon central nervous system, potential genotoxic and cytotoxicity of EMB in human liver cell was ignored and very limited. In this study, we identify genotoxicity and cytotoxicity of EMB to human normal liver cells (QSG7701 cell line) in vitro . We demonstrate that EMB inhibited the viability of QSG7701 cells and induced the DNA damage. Established assays of cytotoxicity were performed to characterize the mechanism of EMB toxicity on QSG7701 cells. Typical chromatin condensation and DNA fragmentation indicated the apoptosis of QSG7701 cells induced by EMB. And the intracellular biochemical results demonstrated that EMB-enhanced apoptosis of QSG7701 cells concurrent with generated ROS, a loss of mitochondrial membrane potential, the cytochrome-c release, up regulate the Bax/Bcl-2 and the activation of caspase-9/-3. Our results of EMB induces the death of QSG7701 cells maybe via mitochondrial-mediated intrinsic apoptotic pathways would contribute to promote the awareness of EMB as an extensive used pesticide to human being effects and reveal the underlying mechanisms of potential genotoxic.