bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural, neuronal, and functional adaptive changes in atrophic rat ileum
Authors: Ekelund K M , Ekblad E 
Published: January 2010

BACKGROUNDInactivity of the gut leads to atrophic changes of which little is known.AIMSTo investigate structural, neuronal, and functional changes occurring in bypassed rat ileum.METHODSMorphometry was used to characterise the atrophic changes. The numbers of enteric neurones, their expression of neurotransmitters, and the presence of interstitial cells of Cajal were studied using immunocytochemistry and in situ hybridisation. Motor activity was studied in vitro.RESULTSAdaptive changes in bypassed ileum include atrophy and remodelling of the gut wall. The total numbers of submucous and myenteric neurones per unit length increased one and four weeks after bypass but were identical to sham operated intestine 10 weeks after bypass. Neurones expressing vasoactive intestinal peptide, neuropeptide Y, or pituitary adenylate cyclase activating peptide decreased gradually in number in bypassed ileum. Nitric oxide synthase expressing neurones were increased, particularly in the myenteric ganglia. No change in the frequency and distribution of interstitial cells of Cajal was noted. The contractile response elicited by electrical stimulation of sham operated ileum consisted of a fast cholinergic twitch followed by a slower non-adrenergic, non-cholinergic contraction. In the bypassed ileum an identical biphasic contraction was elicited; however, the entire response was non-adrenergic, non-cholinergic. The relaxatory response to electrical stimulation in sham operated ileum was nitric oxide mediated; after bypass it was non-nitrergic.CONCLUSIONSNotable atrophic changes were seen in the rat ileum after bypass. The enteric nervous system reacted with neuronal cell death and plasticity in terms of release and expression of neurotransmitters.
Interleukin 1 and interleukin 1β converting enzyme (caspase 1) expression in the human colonic epithelial barrier. Caspase 1 downregulation in colon cancer
Authors: Jarry A , Vallette G , Cassagnau E , Moreau A , Bou-Hanna C , Lemarre P , Letessier E , Le Neel J-C , Galmiche J-P , Laboisse C L 
Published: January 2010

BACKGROUNDInterleukin (IL) 1β converting enzyme (now known as caspase 1) is able to process pro-IL-1β into its active form and is involved in proapoptotic signalling.AIMSTo characterise IL-1 and caspase 1 expression in human colonic epithelial cells.METHODSIntracellular IL-1 content (IL-1α and IL-1β) was measured by ELISA in freshly isolated human normal colonocytes. Caspase 1 expression was determined both at the mRNA level using in situ hybridisation and reverse transcription polymerase chain reaction, and at the protein level by immunoblotting experiments using antibodies specific for the proform of caspase 1 and for its cleavage forms.RESULTSLow amounts of IL-1β were found in nearly all preparations (92%), and IL-1α was detected in only 45% of human colonocyte preparations. The normal colonic epithelium strongly expressed caspase 1, both at the mRNA level and at the protein level in its latent form. In contrast, caspase 1 was not expressed in colon cancer (primary colonic adenocarcinomas and cancer cell lines).CONCLUSIONSThe demonstration that the human colonic epithelial barrier is able to express caspase 1 and its substrate IL-1β reinforces the concept that, under certain conditions, the epithelium could trigger an inflammatory reaction. In addition, the finding that caspase 1 was downregulated in colonic adenocarcinomas supports the concept that disrupted apoptosis pathways may be involved in tumour formation and/or may confer resistance to treatment.
Contribution of matrilysin (MMP-7) to the metastatic pathway of human colorectal cancers
Authors: Adachi Y , Yamamoto H , Itoh F , Hinoda Y , Okada Y , Imai K 
Published: January 2010

BACKGROUND/AIMMatrilysin is one of the matrix metalloproteinases that has a critical role in tumour invasion, and is often expressed in gastrointestinal cancers. The aim of this study was to examine the role of matrilysin in metastasis of human colorectal cancers.PATIENTS (SUBJECTS)/METHODSThe relation between matrilysin expression and Dukes’s type was investigated immunohistochemically in 83 surgically resected colorectal cancers, including five with liver metastasis. Moreover, the effects of matrilysin on the in vivo invasive and metastatic potential of colon cancer cells transfected with matrilysin cDNA were examined after subcutaneous injection into SCID mice.RESULTSIn 46% of primary and all of metastatic liver tumours, over 10% of cancer cells were stained positively for matrilysin. The expression of matrilysin correlated significantly with the presence of nodal or distant metastases (p<0.05). In addition, matrilysin transfectants formed invasive tumours and multiple liver metastases in SCID mice, without producing any significant difference in the subcutaneous tumour growth from mock transfectants. Casein zymography showed that the invading and metastasised tumours showed conspicuous matrilysin activity, which correlated with the number of metastatic lesions (p<0.001).CONCLUSIONSMatrilysin showed a correlation with metastasis in a cohort of 83 colorectal cancer patients and marked metastatic potentiation in human colorectal cancer xenografts, indicating that it may play a critical role in the metastatic pathway of colorectal cancers.
Gall bladder emptying in severe idiopathic constipation
Authors: Penning C , Gielkens H A J , Delemarre J B V M , Lamers C B H W , Masclee A A M 
Published: January 2010

BACKGROUNDIt has been suggested that slow transit constipation (STC) may be part of a panenteric motor disorder.AIMTo evaluate motility of an upper gastrointestinal organ, the gall bladder, in 16 patients with STC and 20 healthy controls.METHODSGall bladder emptying (ultrasonography) was studied in response to neural, cephalic-vagal stimulation with modified sham feeding (MSF) for 90 minutes and in response to hormonal stimulation with cholecystokinin (CCK, 0.5 IDU/kg/h) for 60 minutes.RESULTSFasting gall bladder volume in patients with STC (17 (2) cm3) was significantly (p<0.01) reduced compared with that in controls (24 (2) cm3). Gall bladder emptying in response to MSF was significantly reduced in patients with STC expressed both as percentage emptying (11 (5)% versus 22 (3)%; p<0.05) and as absolute emptying (2.1 (0.7) cm3 versus 4.9 (0.7) cm3; p<0.02). However, percentage gall bladder emptying in response to CCK was not different between patients and controls (73 (4)% versus 67 (4)%) although the absolute reduction in gall bladder volume was significantly (p<0.05) smaller in patients (10.7 (1.1) cm3versus 15.3 (1.4) cm3).CONCLUSIONSPatients with slow transit constipation have smaller fasting gall bladder volumes, impaired gall bladder responses to vagal cholinergic stimulation, but normal gall bladder responses to hormonal stimulation with CCK. These results point to abnormalities in gastrointestinal motility proximal from the colon in slow transit constipation and more specifically, impaired neural responsiveness.
Myofibroblast proliferation, fibrosis, and defective pancreatic repair induced by cyclosporin in rats
Authors: Vaquero E , Molero X , Tian X , Salas A , Malagelada J-R 
Published: January 2010

BACKGROUNDFull recovery is always achieved after caerulein induced pancreatitis. Cyclosporin stimulates transforming growth factor β (TGF-β) and may interfere with pancreatic regeneration.AIMTo investigate the effects of cyclosporin after caerulein induced pancreatitis or after caerulein injury.METHODSProtocol A: rats received cyclosporin daily (20 mg/kg) and caerulein pancreatitis was induced on days 2 and 8. Protocol B: six courses of caerulein pancreatitis were induced at weekly intervals. Cyclosporin was administered on induction and the day before. Rats recovered for two weeks before being killed. Control groups received saline, cyclosporin, or caerulein alone.RESULTSProtocol A: plasma TGF-β1 and tissue collagenase rose after pancreatitis but decreased towards baseline values on day 15, matching a low collagen content. Morphology disclosed minimal inflammatory infiltration and some interstitial cells immunoreactive for smooth muscle α-actin (SMA). TGF-β1 increased, and remained high in cyclosporin treated groups (cyclosporin alone and cyclosporin plus caerulein). Rats treated with cyclosporin and caerulein showed severe pancreatic weight reduction, abundant inflammatory infiltrates, increased SMA immunoreactive interstitial cells, high collagen content, and delayed collagenase response. No SMA immunoreactive cells were detected in normal rats. Cyclosporin alone also increased SMA immunoreactive cells, despite the absence of inflammatory infiltration and fairly conserved pancreatic structure. Protocol B: the combined pulse treatment induced appreciable collagen deposition and resulted in a smaller pancreas than controls. Morphological examination showed atrophy, fibrosis, fibroblast proliferation, and mononuclear infiltrates.CONCLUSIONCyclosporin greatly distorts pancreatic repair, transforming caerulein induced pancreatitis into a fibrotic chronic-like disease. The mechanism involves TGF-β, myofibroblasts, and defective collagenase activation.
Iron overload in urban Africans in the 1990s
Authors: Gangaidzo I T , Moyo V M , Saungweme T , Khumalo H , Charakupa R M , Gomo Z A R , Loyevsky M , Stearman R , Vaute T La , Enquist E G , Rouault T A , Gordeuk V R 
Published: January 2010

BACKGROUNDIn a previously described model, heterozygotes for an African iron loading locus develop iron overload only when dietary iron is high, but homozygotes may do so with normal dietary iron. If an iron loading gene is common, then homozygotes with iron overload will be found even in an urban population where traditional beer, the source of iron, is uncommon.AIMSTo determine whether iron overload and the C282Y mutation characteristic of hereditary haemochromatosis are readily identifiable in an urban African population.METHODSHistological assessment, hepatocellular iron grading, and dry weight non-haem iron concentration were determined in post mortem tissue from liver, spleen, heart, lungs, and skin. DNA of subjects with elevated hepatic iron indexes was analysed for the C282Y mutation. Iron concentrations in other tissues were compared.RESULTSA moderate increase (>30 μmol/g) in hepatic iron concentrations was found in 31 subjects (23%; 95% confidence interval 15.9 to 30.1%), and they were considerably elevated (>180 μmol/g) in seven subjects (5.2%; 95% confidence interval 1.5 to 8.9%). Appreciably elevated hepatic iron concentrations were associated with heavy iron deposition in both hepatocytes and macrophages, and either portal fibrosis or cirrhosis. All were negative for the C282Y mutation. Very high concentrations were uncommon in subjects dying in hospital. Concentrations of iron in spleen, heart, lung, and skin were significantly higher in subjects with elevated hepatic iron.CONCLUSIONSIron overload is readily identified among urban Africans and is associated with hepatic damage and iron loading of several tissues. The condition is unrelated to the genetic mutation found in hereditary haemochromatosis.
High prevalence of anti-hepatitis B virus serological markers in patients with hepatitis C virus related chronic liver disease in Japan
Authors: Marusawa H , Osaki Y , Kimura T , Ito K , Yamashita Y , Eguchi T , Kudo M , Yamamoto Y , Kojima H , Seno H , Moriyasu F , Chiba T 
Published: January 2010

BACKGROUND/AIMSEvidence is accumulating that hepatitis B virus (HBV) is present in patients who are hepatitis B surface antigen negative but have antibody to hepatitis B core antigen (anti-HBc). Furthermore, recent studies have shown that patients with hepatocellular carcinoma who have antibody to hepatitis C virus (HCV) often possess HBV related serological markers. Data on the seroprevalence of HBV infection in patients with HCV related chronic liver disease were collected to evaluate the significance of the presence of antibodies to HBV.METHODSThe prevalence of HBV related serological markers was analysed in a total of 2014 Japanese patients with HCV infection. The control group comprised 352 subjects without liver disorder.RESULTSA large number of patients (49.9%) with HCV related chronic liver disease including hepatocellular carcinoma were positive for anti-HBc. In addition, the prevalence of anti-HBc closely correlated with the clinical stage of the liver disease. There was no relation between a past history of blood transfusion and the prevalence of anti-HBc. Notably, anti-HBc was the only serological marker for HBV infection in a significant number of patients with HCV related chronic liver disease (24.1%).CONCLUSIONSOur data provide further evidence for the high prevalence of anti-HBc in patients with HCV related chronic liver disease, particularly those with hepatocellular carcinoma, suggesting that HBV infection, probably including latent infection, may play an important role in carcinogenesis in these patients.
Familial occurrence of nodular regenerative hyperplasia of the liver: a report on three families
Authors: Dumortier J , Boillot O , Chevallier M , Berger F , Potier P , Valette P-J , Paliard P , Scoazec J-Y 
Published: January 2010

BACKGROUND/AIMSNodular regenerative hyperplasia of the liver is a histological lesion usually associated with systemic diseases, haematological malignancies, or drugs. Its prognosis depends on portal hypertension, which usually is well tolerated and requires medical management only.PATIENTSThree unrelated families, in which two sibling adult male patients presented with nodular regenerative hyperplasia of the liver, were studied.METHODSComplete clinical charts and liver biopsy specimens were available for all patients. In addition, explanted livers were available for examination for the two transplanted patients.RESULTSThere was no evidence of any of the various clinical situations known to be associated with nodular regenerative hyperplasia of the liver. Portal hypertension was severe, requiring surgical treatment in two cases. Renal lesions were present in three patients. In two patients, progressive evolution to liver atrophy and hepatic failure, associated with renal failure, led to combined liver and renal transplantation.CONCLUSIONSThis report describes the existence of familial cases of nodular regenerative hyperplasia of the liver, occurring without underlying or associated systemic disease, characterised by a poor clinical course and often associated with progressive renal failure.
Development of a disease specific questionnaire to measure health related quality of life in patients with chronic liver disease
Authors: Younossi Z M , Guyatt G , Kiwi M , Boparai N , King D 
Published: January 2010

BACKGROUND AND AIMSTo develop and assess a disease specific instrument for measuring health related quality of life (HRQL) in patients with chronic liver disease (CLD).METHODSBased on responses from 60 patients with chronic liver disease, from 20 liver experts, and from a Medline search of the literature, items potentially affecting the HRQL of these patients were identified. A separate sample of 75 patients identified which items they found problematic and rated their importance. Results were explored using factor analysis; domains were chosen and items placed within domains. Redundant questions were eliminated and the final questionnaire was pretested in 10 patients. Using this instrument, HRQL was assessed in a further 133 patients with various types and stages of liver disease.RESULTSPatients, experts, and the literature search identified 156 items of potential importance. Of these, 35 proved important to over 50% of 75 respondents in the item reduction sample. The factor analysis suggested six domains. After eliminating redundancies, the Chronic Liver Disease Questionnaire (CLDQ) included 29 items in the following domains: fatigue, activity, emotional function, abdominal symptoms, systemic symptoms, and worry. In pretesting, patients found the CLDQ clear and easy to complete in 10 minutes. In another 133 patients, the CLDQ showed a gradient between patients without cirrhosis, Child’s A cirrhosis, and those with Child’s B or C cirrhosis. CLDQ has evidence for moderate reliability at six months and seems to be responsive.CONCLUSIONThe CLDQ is short, easy to administer, produces both a summary score and domain scores, and correlates with the severity of liver disease.
Spur cell anaemia and hepatic iron stores in patients with alcoholic liver disease undergoing orthotopic liver transplantation
Authors: Pascoe A , Kerlin P , Steadman C , Clouston A , Jones D , Powell L , Jazwinska E , Lynch S , Strong R 
Published: January 2010

BACKGROUNDFollowing orthotopic liver transplantation (OLT) histological examination of explant livers from patients with alcoholic liver disease (ALD) sometimes shows extensive iron deposits in a distribution suggestive of homozygous haemochromatosis.AIMSTo use haemochromatosis gene (HFE) assays to distinguish between ALD with notable siderosis and hereditary haemochromatosis. To evaluate the possible influence of spur cell haemolytic anaemia on hepatic iron loading.PATIENTSThirty seven patients with ALD were abstinent for at least six months prior to OLT. Twenty three patients had transferrin saturations greater than 55%, 16 also had increased serum ferritin (>350 μg/l). Eight of 37 (22%) explant livers had grade 3 or 4 hepatic iron deposition, predominantly in hepatocytes. Of these, four had a hepatic iron index greater than 1.9 and most seemed to have spur cell haemolytic anaemia.METHODSMutation analysis for C282Y and H63D mutations was performed on DNA extracts from peripheral blood or explant liver. Spur cell haemolytic anaemia was diagnosed when the haemoglobin was 105 g/l in the presence of notable acanthocytosis.RESULTSNone of the eight patients with grade 3 or 4 hepatic iron had evidence of the C282Y mutation. Two of the eight were heterozygous for H63D. None of the remaining 28 patients tested showed homozygous HFE mutations. Spur cell anaemia was present in six of the eight patients with heavy iron deposition and only one of the remaining patients.CONCLUSIONSThe HFE mutation was not present in these patients with advanced ALD and heavy iron loading. Spur cell haemolytic anaemia provides an alternative potential mechanism for the heavy iron loading.
Selection of hepatitis B surface “escape” mutants during passive immune prophylaxis following liver transplantation: potential impact of genetic changes on polymerase protein function
Authors: Shields P L , Owsianka A , Carman W F , Boxall E , Hubscher S G , Shaw J , O’Donnell K , Elias E , Mutimer D J 
Published: January 2010

CASE REPORTA patient is described who developed hepatitis B virus (HBV) reinfection five months following liver transplantation. Failure of hepatitis B immunoglobulin prophylaxis was associated with the emergence of mutations. HBV gene sequencing identified nucleotide substitutions associated with amino acid changes, one within the major hydrophilic region (MHR) of the HBV surface antigen at amino acid position 144 and one outside the MHR. Because of the overlapping reading frames of surface and polymerase genes, the latter surface antigen change was associated with an amino acid change in the polymerase protein. The patient developed significant allograft hepatitis and was treated with lamivudine (3TC) 100 mg daily. Rapid decline of serum HBV DNA was observed with loss of HBV e antigen and HBV surface antigen from serum. There was normalisation of liver biochemistry, and liver immunohistochemistry showed a reduction in HBV core and disappearance of HBs antigen staining.CONCLUSIONSurface antigen encoding gene mutations associated with HBIg escape may be associated with alteration of the polymerase protein. The polymerase changes may affect sensitivity to antiviral treatment. Selection pressure on one HBV reading frame (for example, HBIg pressure on HBsAg, or nucleoside analogue pressure on polymerase protein) may alter the gene product of the overlapping frame. Such interactions are relevant to strategies employing passive immune prophylaxis and antiviral treatment.
Evaluation of a policy to reduce youth tractor crashes on public roads
Authors: Marlenga B , Doty B C , Berg R L , Linneman J G 
Published: January 2010

Objective:Evaluate the effectiveness of a United States state law, Wisconsin Act 455, in reducing highway tractor crashes involving youth operators.Design:Policy outcome evaluation involving review of a retrospective case series.Setting:Youth highway tractor crashes from Wisconsin for the years 1994–2003 that resulted in a fatality, injury, and/or property damage.Subjects:One hundred and forty six tractor crash cases involving operators younger than 16 years.Methods:Describe and model the tractor crash patterns before and after enactment of the law, and examine the relation between the contributing circumstances identified in the crash reports and the content covered in the mandated tractor certification course.Results:There was neither a significant change in the number of youth tractor crashes after the law was passed, nor any reduction in the proportion of crashes where the youth operator was designated at fault. The tractor certification course did not cover the major factors contributing to youth tractor crashes on public roads.Conclusions:No significant effect of the law was detected and crash rates at the end of the study period were similar to those before Wisconsin Act 455. The authors’ findings should not be construed to suggest that public policy, in general, is an ineffective strategy for the prevention of pediatric agricultural injuries. Negotiating a balance in public policy debates will be a challenge, but it is clear that future policy initiatives need to identify and implement the right policy for the right problem.
Identification of DJ-1/PARK-7 as a determinant of stroma-dependent and TNF-α–induced apoptosis in MDS using mass spectrometry and phosphopeptide analysis
Authors: Marcondes A. Mario , Li Xiang , Gooley Ted A. , Milless Brian , Deeg H. Joachim 
Published: January 2010

AbstractIn patients with myelodysplastic syndromes (MDS), apoptosis in hematopoietic cells is up-regulated in low-grade disease, whereas advanced disease is characterized by apoptosis resistance. We have shown that marrow stroma–derived signals convey sensitivity to tumor-necrosis-factor alpha (TNF-α)–mediated apoptosis in otherwise-resistant KG1a myeloid cells and CD34+ cells from MDS marrow. Here, we used a PhosphoScan proteomic liquid chromatography–mass spectrometry method to identify signals relevant for this effect. The transcription factor DJ-1/PARK-7 (DJ-1) was highly phosphorylated in KG1a cells cultured without stroma but dephosphorylated after stroma coculture, whereas expression of p53 increased significantly, suggesting a stroma contact-dependent effect of DJ-1 on p53. In CD34+ marrow cells from advanced MDS, expression of DJ-1 was up-regulated, whereas p53 levels were low, resulting in significantly greater DJ-1/p53 ratios than in patients with low-grade MDS (P = .01). DJ-1 levels were correlated with increasing International Prognostic Scoring System scores (P = .006). Increasing DJ-1/p53 ratios were associated with an increased risk of mortality, although the correlation did not reach statistical significance (P = .18). These data suggest that DJ-1/p53 interactions contribute to apoptosis resistance in clonal myeloid cells and may serve as a prognostic marker in patients with MDS.