bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibodies directed to pig non‐Gal antigens in naïve and sensitized baboons
Authors: Ezzelarab Mohamed , Hara Hidetaka , Busch Jamie , Rood Pleunie P. M. , Zhu Xiaocheng , Ibrahim Zuhaib , Ball Suyapa , Ayares David , Awwad Michel , Cooper David K. C. 
Published: August 2006

Abstract:  Background:  As pigs homozygous for α1,3‐galactosyltransferase gene‐knockout (GT‐KO) are available, primate antibodies to pig non‐Gal antigens can be studied.Methods:  Sera from 56 baboons were tested for binding of IgM and IgG to peripheral blood mononuclear cells (PBMC) from both wild‐type (WT) and GT‐KO pigs by flow cytometry. Complement‐dependent cytotoxicity was measured in 39 sera. Antibody and cytotoxicity responses were measured in two baboons exposed to a GT‐KO pig heart, one not immunosuppressed and one that received only cobra venom factor.Results:  IgM and IgG bound to 95% and 79% of WT PBMC, and 32% and 9% GT‐KO PBMC, respectively (WT vs. GT‐KO, P < 0.01). Whereas 97% of sera were cytotoxic to WT PBMC, only 64% were cytotoxic to GT‐KO PBMC, and the level of cytotoxicity was less (mean 60% vs. 25% lysis, P < 0.05). In the two baboons exposed to GT‐KO hearts, anti‐non‐Gal antibodies increased markedly, peaking after 2 (IgM) and 3 (IgG) weeks, associated with an increase in lysis of GT‐KO PBMC.Conclusions:  Two‐thirds of baboon sera demonstrated cytotoxicity to GT‐KO PBMC. After GT‐KO organ transplantation, if an elicited antibody response develops, it is likely to cause rapid graft rejection.
Hospital personnel faced with organ xenotransplantation: an attitudinal survey in a hospital with a pre‐clinical liver xenotransplantation program
Authors: Ríos A. , Conesa C. , Ramírez P. , Galindo P.J. , Rodríguez M.M. , Martínez L , Montoya M.J. , Rodríguez J.M. , Parrilla P. 
Published: August 2006

Abstract: Background: In situations of extreme urgency when there is a need for vital organs, xenotransplantation could provide a bridge until the arrival of a human organ. However, it is important to find out the level of acceptance of this potential therapy among the health care workers who would be involved in its implementation. The objective of this study is to analyze attitude among personnel in a hospital with a pre‐clinical xenotransplantation program toward xenotransplantation and to determine the variables that influence this attitude.Materials and methods: A random sample (n = 1168) was taken and stratified according to job category and service. Attitude toward xenotransplantation was evaluated using a validated questionnaire. Contact was made with the head of each service who was given an explanation of the project. This person was made responsible for the distribution and collection of the survey in each service in randomly selected work shifts. Such a survey was completed anonymously and was self‐administered. A random sample of 250 individuals from our regional community was used as a control group.Results: The survey completion rate was 98% (n = 1148). Most respondents are in favor (67%), 7% are against and 26% undecided. Such an attitude is more favorable in the control group (74% vs. 67%; P = 0.0378). The following factors are positively related to such an attitude: (1) male sex (P < 0.0005); (2) a younger age (P = 0.013); (3) participation in prosocial voluntary activities (P = 0.002); (4) knowing that the church has a positive attitude toward donation and transplantation (P < 0.0005); (5) a partner's favorable attitude toward transplantation (P < 0.0005); (6) a physician's job category (P < 0.0005); (7) a resident physician's job contract situation (P = 0.017); (8) a respondent's belief that he or she may need a transplant in the future (P < 0.0005); and (9) a favorable attitude toward human donation, whether this be cadaveric or living (P < 0.0005). In the multivariate analysis, the following persist as independent variables: (1) sex (odds ratio = 1.6); (2) participation in prosocial voluntary activities (odds ratio = 2.2); (3) a partner's unfavorable attitude toward transplantation (odds ratio = 0.3); (4) a favorable attitude toward cadaveric donation (odds ratio = 2); and (5) attitude toward living liver donation (odds ratio = 3.8).Conclusions: Attitude toward xenotransplantation is not as favorable among hospital personnel as it is in the general public and this is determined by many factors. It will be necessary for research groups to periodically carry out awareness‐raising activities about our findings in our own centers, to avoid the rejection that could be generated by a lack of awareness.
Pancreas storage in oxygenated perfluorodecalin does not restore post‐transplant function of isolated pig islets pre‐damaged by warm ischemia
Authors: Brandhorst Daniel , Iken Marcus , Bretzel Reinhard G. , Brandhorst Heide 
Published: August 2006

Abstract:  Background:  Cold storage in oxygenated perfluorodecalin (PFD) restores transplant function of ischemically damaged dog pancreata and reduces the impact of cold ischemia on recovery of isolated human islets. Whether PFD storage can improve islet isolation from pancreata exposed to significant warm ischemia (WI) is unclear yet. The present study aimed to clarify this question in adult pigs.Methods:  After exsanguination, the intestine was removed immediately or left in the cavity for 30 min of WI. Resected pancreata were intraductally flushed with cold University of Wisconsin solution. Subsequently, pancreata were processed immediately by digestion‐filtration (group I: 0 min WI, n = 6; II: 30 min WI, n = 6) or first stored for 3 h in oxygenated PFD (III: 0 min WI + PFD, n = 5; IV: 30 min WI + PFD, n = 6).Results:  Pancreata subjected to 30 min of WI yielded significantly less islets compared with the corresponding non‐ischemic organs (I vs. II, P < 0.01; III vs. IV, P < 0.05). Oxygenation did not ameliorate the loss in islet yield (II vs. IV, NS). Ischemic islets were characterized by depleted ATP stores (388 ± 73 (I) vs. 133 ± 22 ng/1000 IEQ (II), P < 0.01) and diminished insulin response to glucose calculated as stimulation index (SI; 2.47 ± 0.36 (I) vs. 0.25 ± 0.17 (II), P < 0.05). PFD storage of ischemic organs partially restored ATP content (217 ± 23 ng/1000 IEQ, II vs. IV, P < 0.05) and glucose SI (1.60 ± 0.09, II vs. IV, P < 0.05) to a significant extent that reached the level of corresponding PFD‐stored, non‐ischemic pancreata (III vs. IV, NS). Sustained normoglycemia was exclusively observed in diabetic nude mice transplanted with islets isolated from non‐ischemic organs. The significantly reduced graft function of ischemic islets (I vs. II, III vs. IV, P < 0.001) was not increased by pancreatic oxygenation (II vs. IV, NS).Conclusions:  The present study suggests that pancreas short‐term storage in oxygenated PFD improves in vitro but not the in vivo function of ischemically damaged pig islets.
Creutzfeldt–Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiological Review study
Authors: Hewitt P. E. , Llewelyn C. A. , Mackenzie J. , Will R. G. 
Published: August 2006

Background and Objectives  This paper reports the results to 1 March 2006 of an ongoing UK study, the Transfusion Medicine Epidemiological Review (TMER), by the National CJD Surveillance Unit (NCJDSU) and the UK Blood Services (UKBS) to determine whether there is any evidence that Creutzfeldt–Jakob disease (CJD), including sporadic CJD (sCJD), familial CJD (fCJD), and variant CJD (vCJD) is transmissible via blood transfusion.Materials and Methods  Sporadic CJD and fCJD cases with a history of blood donation or transfusion are notified to UKBS. All vCJD cases aged > 17 years are notified to UKBS on diagnosis. A search for donation records is instigated and the fate of all donations is identified by lookback. For cases with a history of blood transfusion, hospital and UKBS records are searched to identify blood donors. Details of identified recipients and donors are checked against the NCJDSU register to establish if there are any matches.Results  CJD cases with donation history: 18/31 vCJD, 3/93 sCJD, and 3/5 fCJD cases reported as blood donors were confirmed to have donated labile components transfused to 66, 20, and 11 recipients respectively. Two vCJD recipients have appeared on the NCJDSU register as confirmed and probable vCJD cases. The latter developed symptoms of vCJD 6.5 years and 7.8 years respectively after receiving non‐leucodepleted red blood cells (RBCs) from two different donors who developed clinical symptoms approximately 40 and 21 months after donating. A third recipient, given RBC donated by a further vCJD case approximately 18 months before onset of clinical symptoms, had abnormal prion protein in lymphoid tissue at post‐mortem (5‐years post‐transfusion) but had no clinical symptoms of vCJD. CJD cases with history of transfusion: Hospital records for 7/11 vCJD and 7/52 sCJD cases included a history of transfusion of labile blood components donated by 125 and 24 donors respectively. Two recipients who developed vCJD were linked to donors who had already appeared on the NCJDSU register as vCJD cases (see above). No further links were established.Conclusion  This study has identified three instances of probable transfusion transmission of vCJD infection, including two confirmed clinical cases and one pre‐ or sub‐clinical infection. This study has not provided evidence, to date, of transmission of sCJD or fCJD by blood transfusion, but data on these forms of diseases are limited.
Welfare Index and Reproductive Performance in the Sow
Authors: Munsterhjelm C , Valros A , Heinonen M , Hälli O , Peltoniemi OAT 
Published: August 2006

ContentsTo study the relationship between on‐farm welfare and reproductive performance in the sow, the TGI 35L Animal Needs Index was modified for use in Finnish pig production. The modified index had a maximal total score of 100. It was comprised of six categories: ‘locomotion’ (maximal score 21 for dry sows and 11 for lactating sows), ‘social interaction’ (12/8), ‘floor quality’ (16/9), ‘stable climate’ (16/21), ‘feeding’ (16/23) and ‘health and stockmanship’ (19/29). Index scorings were performed separately in farrowing, breeding and gestation units on 28 representative Finnish sow farms. One‐year production parameters were collected. Multiple linear regression was used for statistical analysis. Total ANI‐points varied between 36.5–68.0 for lactating and 39.5–86.0 for dry sows. Litter size increased with increasing scores for ‘feeding’ in the dry sow unit. Controlling for breed, high scores for ‘health and stockmanship’ and ‘floor quality’ shortened the reproductive cycle, probably because of good leg health. The number of weaned piglets per sow per year (PSY) increased with increasing scores for dry sow ‘health and stockmanship’, ‘floor quality’ and an interaction of ‘feeding’ in the farrowing and mating units. PSY increased with decreasing scores for farrowing pen ‘climate’. High‐quality floors and stockmanship appear to correlate positively with reproductive performance in the sow. Effects of a welfare‐promoting feeding strategy on reproduction are contradictory.
Teaching Bovine Rectal Palpation with Live Cows in the Slaughterhouse: Is it Worthwhile?
Authors: Lopes G , Rocha A 
Published: August 2006

ContentsBovine rectal palpation, a procedure that requires considerable practice to develop the necessary skills, is often taught during extramural activities, or even learnt in practice after graduation. However, student access to cows in extramural activities may be limited because of student numbers, animal welfare considerations and concerns over induction of embryo mortality because of inexperience of the student. To overcome some of these limitations, in our school practical classes of bovine rectal palpation are taught in a slaughterhouse, with small groups of approximately 10 students per class, over a period of 30 weeks. Number of cows palpated, type of cases found and the success rate of students in the final practical exam were recorded and analysed for 3 years, and contrasted with the pre‐established goals for the course. Additionally, a questionnaire was sent to former students to assess their opinion on the usefulness of the palpation course, as well as to identify main learning difficulties and collect suggestions to improve teaching methods. Overall, the information obtained indicated that the course is useful to teach palpation skills, even if the original goals may have been very optimistic. Most (96%) of the respondents had the opinion that the course was very useful or useful. Several suggestions were offered to improve teaching methods, but there was no consensus on a single recommendation. Despite the fact that a considerable number of respondents to the questionnaire did not use bovine rectal palpation in their practice, only one considered the classes ‘not useful’. It is concluded that this method of teaching rectal palpation should be continued and the teaching methods improved with the adoption of some modifications.
Cell death in pancreatitis: Effects of alcohol
Authors: Gukovskaya Anna S , Mareninova Olga A , Odinokova Irina V , Sung Kai‐Feng , Lugea Aurelia , Fischer Lars , Wang Yan‐Ling , Gukovsky Ilya , Pandol Stephen J 
Published: August 2006

AbstractPancreatitis is a severe and frequently lethal disorder, a major cause of which is alcohol abuse. Parenchymal cell death is a major complication of pancreatitis. In experimental models of (non‐alcoholic) acute pancreatitis, acinar cells have been shown to die through both necrosis and apoptosis, the two principal pathways of cell death. The severity of experimental acute pancreatitis correlates directly with the extent of necrosis and inversely with apoptosis. Thus, understanding the regulation of apoptosis and necrosis, and whether it is possible to manipulate the pattern of death responses, is becoming exceedingly important in investigations of the pathogenesis and treatment of pancreatitis. The effects of alcohol on cell death responses of pancreatitis, and the mechanisms that may mediate these effects, are just starting to be explored. This paper reviews the signaling pathways mediating the balance between apoptosis and necrosis in acute pancreatitis, and alcohol’s effects on cell death responses in pancreatitis.
In vivo imaging of hepatic fatty acid metabolism in patients with non‐alcoholic steatohepatitis using semiquantitative 123I‐labeled branched‐chain fatty acid analog
Authors: Onishi Saburo , Saibara Toshiji 
Published: August 2006

AbstractObesity is now prevailing worldwide, coincident with the increase of hepatic steatosis. Metabolic syndrome with obesity and hypertension, hyperlipidemia, and impaired glucose tolerance is one of the most frequent life‐threatening diseases and non‐alcoholic steatohepatitis is believed to be a hepatic expression of this syndrome. Non‐alcoholic steatohepatitis is prevalent and well characterized in Caucasians, but little is known about non‐alcoholic steatohepatitis in Asia–Oceania. Obesity will be a serious social problem in Asia–Oceania in the next two decades and we need to prevent the increase of this syndrome. Therefore, it is extremely important to know about non‐alcoholic steatohepatitis based on racial differences, because this syndrome is likely to be a multi‐factorial syndrome resulting from different combinations of susceptibility genes superimposed on different environmental factors. Because hepatic steatosis is the first step in the development of not only metabolic syndrome but also non‐alcoholic steatohepatitis, the genetic background of Japanese NASH patients was investigated and a measure to assess fatty acid β‐oxidation in the liver in vivo was developed.
Update on pancreatic cancer and alcohol‐associated risk
Authors: Welsch Thilo , Kleeff Jörg , Seitz Helmut K , Büchler Peter , Friess Helmut , Büchler Markus W 
Published: August 2006

AbstractDuctal adenocarcinoma of the pancreas is characterized by extremely aggressive behavior, with an overall 5‐year survival of <4%. Because conventional and specifically tailored therapeutic regimens have little impact on patient survival, epidemiological and molecular research aims at identifying and reducing risk factors. Cigarette smoking, obesity, diabetes mellitus, and chronic pancreatitis are amenable to medical prevention or therapy. Heavy alcohol consumption is an inconsistent single risk factor for pancreatic cancer but may promote carcinogenesis by increasing the risk of diabetes mellitus or chronic pancreatitis. For various agents, the key carcinogenic effect is probably an inflammatory response in the pancreatic tissue. On the molecular level, mutations of oncogenes and tumor suppressor genes, as well as various epigenetic alterations, such as overexpression of growth factors and their receptors, are important in tumorigenesis. Complete and safe surgical resection, together with adjuvant therapy, offers prolonged survival, with 5‐year survival rates of approximately 25%. However, for unresectable or disseminated disease, which constitutes the vast majority of cases, treatment is palliative. Despite increasing knowledge about the molecular pathology of pancreatic cancer and despite advances in treatment, the overall course of the disease is dismal, and reinforced efforts to reduce incidence and improve outcome are needed desperately.
Vacuolar adenosine triphosphatase and pancreatic acinar cell function
Authors: Gorelick Fred S , Shugrue Christine A , Kolodecik Thomas R , Thrower Edwin C 
Published: August 2006

AbstractThe pathologic activation of proteases within the pancreatic acinar cell is a key initiating event in acute pancreatitis. Past studies have suggested that the generation of a low‐pH environment is critical to this process. Vacuolar adenosine triphosphatase (vATPase) is a multiprotein complex that transports protons across cellular membranes. Activation of the vATPase requires assembly of the soluble (V1) subunits on the membrane subunits (V0). It is found that conditions that cause protease activation in the acinar cell also cause assembly of V1 on V0. Further, inhibitors of vATPase block this protease activation. Ethanol and butanol sensitize the acinar cell to cholecystokinin‐induced zymogen activation; vATPase inhibitors also blocked this activation. Activation of the vATPase may be central to the pathologic activation of proteases in the acinar cell and may also modulate the sensitizing effects of alcohols.
Role of Ca2+ in pancreatic cell death induced by alcohol metabolites
Authors: Criddle David N , Sutton Robert , Petersen Ole H 
Published: August 2006

AbstractWhereas alcohol itself, even in high concentrations, has little effect on the functional performance of isolated pancreatic acinar cells, non‐oxidative metabolites (fatty acid ethyl esters [FAEE] and fatty acids [FA]) can cause Ca2+‐dependent necrosis. The mechanism of action of FAEE has been investigated using a combination of patch clamp whole‐cell current recording and Ca2+ imaging. At low stimulation intensities, FAEE evoke repetitive short‐lasting cytosolic Ca2+ spikes, which are inhibited by caffeine, used as an inositol trisphosphate receptor antagonist. With more intense stimulation, sustained elevations of the cytosolic Ca2+ concentration are observed, which can be prevented by pharmacological inhibition of the conversion of FAEE to FA. It is therefore the FA and not the FAEE that cause necrosis. The effect of FA cannot be blocked by inositol trisphosphate receptor antagonists. Fatty acids elicit a marked reduction in the cytosolic adenosine triphosphate (ATP) level. The patch clamp experiments show that the toxic sustained Ca2+ signal generation induced by FA can be prevented by adding ATP to the cell interior. The toxic alcohol effects are principally due to FAEE produced under non‐oxidative conditions and their subsequent conversion to FA. The FA‐induced necrosis is Ca2+‐dependent. The destructive sustained Ca2+ signals are due to inhibition of mitochondrial function with failure of ATP generation.
SPINK1 gene mutations and pancreatitis in Japan
Authors: Shimosegawa Tooru , Kume Kiyoshi , Masamune Atsushi 
Published: August 2006

AbstractSPINK1 can inhibit up to 20% of trypsin activity, and may constitute one major mechanism to protect the pancreas from autodigestion. In 2000, Witt et al. first recognized the association between mutations in the SPINK1 gene and chronic pancreatitis (CP), but the significance of SPINK1 gene mutation in pancreatitis and its relation to alcohol consumption remains unclear in Japan. The aim of the present paper was to clarify the incidence of SPINK1 mutations in CP patients with various etiologies in Japan and, in addition, to examine the relationship between alcohol metabolism and the polymorphisms in the key enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase‐2 (ALDH2). A total of 156 patients with CP, and 165 healthy volunteers, all Japanese, were examined for the SPINK1 mutations by polymerase chain reaction–restriction fragment length polymorphism and direct sequencing. In Japan, the prevalence of [N34S; IVS1–37T > C] and [−215G > A; IVS3 + 2T > C] was significantly higher in patients with idiopathic CP (10.6% and 12.8%, respectively) than normal subjects (0.6% and 0%). The frequency of the [−215G > A; IVS3 + 2T > C] mutation in Japan was significantly higher than that reported in other populations. Concerning alcoholic CP, the [−215G > A; IVS3 + 2T > C] mutation was found in only a small number of patients (3.9%). On analysis of ADH2 and ALDH2 gene polymorphisms an association was found between ADH2*2 allele and alcoholic CP, and the ADH2*2/2*2 genotype had a tendency to increase the risk of developing pancreatic pseudocyst. In conclusion, in Japan the [−215G > A; IVS3 + 2T > C] mutation in the SPINK1 gene may form a unique genetic background for pancreatitis.
Cytochrome P450 2E1‐dependent oxidant stress and upregulation of anti‐oxidant defense in liver cells
Authors: Cederbaum Arthur I 
Published: August 2006

AbstractInduction of cytochrome P450 2E1 (CYP2E1) is a central pathway by which ethanol generates oxidative stress. Cytochrome P450 2E1 metabolizes many other toxicologic compounds. Toxicity of these agents is enhanced by ethanol, due to induction of CYP2E1. Cytochrome P450 2E1 is induced under a variety of physiological and pathophysiological conditions. The laboratory at Mount Sinai School of Medicine established HepG2 cell lines that constitutively express human CYP2E1. Ethanol, polyunsaturated fatty acids and iron were toxic to the HepG2 cells that express CYP2E1 (E47 cells) but not control HepG2 cells. The E47 cells had higher glutathione levels than control HepG2 cells due to activation of the genes encoding the heavy and light subunits of gamma glutamyl cysteine synthetase (GCLC and GCLM). There was also a twofold increase in catalase, cytosolic and microsomal glutathione transferase, and heme oxygenase‐1 (HO‐1) in the E47 cells due to activation of their respective genes. These activations were prevented by anti‐oxidants, suggesting that the upregulation of these anti‐oxidant genes may reflect an adaptive mechanism to remove CYP2E1‐derived oxidants. Increases in nuclear factor erythroid 2‐related factor 2 (Nrf2) protein and mRNA were observed in livers of hepatocytes of chronic alcohol‐fed and of pyrazole‐treated rats or mice, conditions known to elevate CYP2E1. E47 cells showed increased Nrf2 mRNA and protein expression. Upregulation of GCLC and HO‐1 in E47 cells is dependent on Nrf2. These results suggest that Nrf2 is activated and its levels are increased when CYP2E1 is elevated. It is suggested that Nrf2 plays a key role in the adaptive response against increased oxidative stress caused by CYP2E1.