bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of the route of sensitization on local and systemic immune responses in a murine model of type I allergy
Authors: REPA A , WILD C , HUFNAGL K , WINKLER B , BOHLE B , POLLAK A , WIEDERMANN U 
Published: June 2004

SUMMARYThe pathophysiological and immunological characteristics of allergic immune responses are controlled by a variety of factors. We have studied the extent to which the route of sensitization influences allergen-specific IgE synthesis and local airway inflammation using a mouse model of allergic sensitization to the major birch pollen allergen Bet v 1. Sensitization of BALB/c mice with recombinant (r)Bet v 1 was performed using intraperitoneal (IP), subcutaneous (SC) or aerosol (AS) sensitization protocols. Mice were analysed for allergen-specific serum antibodies by ELISA and IgE-dependent basophil degranulation. Proliferative responses and cytokine production of splenocytes were measured upon Bet v 1 stimulation in vitro. Bronchoalveolar lavages were performed after airway challenge with aerosolized birch pollen extract for assessment of eosinophilic airway inflammation and local cytokine production in vivo. Highest allergen specific IgE levels and IgE-dependent basophil degranulation were achieved using the SC route. High IL-5 production by spleen and lung cells was associated with pronounced eosinophilia in bronchoalveolar lavages. After IP sensitization, despite giving the highest IgG levels, only low IgE levels, basophil degranulation and IL-5 production were seen. On the other hand, AS sensitization, resulting in the lowest systemic IgE and IL-5 levels, led to a comparably strong airway inflammation as the SC route. Our finding that the route of sensitization can result in a dissociation of local and systemic immune responses may contribute to a better understanding of the pathogenesis of allergic diseases and help to develop new treatment strategies.
Oral tolerization with peptide 336–351 linked to cholera toxin B subunit in preventing relapses of uveitis in Behcet's disease
Authors: STANFORD M , WHITTALL T , BERGMEIER L A , LINDBLAD M , LUNDIN S , SHINNICK T , MIZUSHIMA Y , HOLMGREN J , LEHNER T 
Published: June 2004

SUMMARYBehcet's disease (BD) specific peptide (p336–351) was identified within the human 60 kD heat shock protein (HSP60). Oral p336–351 induced uveitis in rats which was prevented by oral tolerization with the peptide linked to recombinant cholera toxin B subunit (CTB). This strategy was adopted in a phase I/II clinical trial by oral administration of p336–351-CTB, 3 times weekly, followed by gradual withdrawal of all immunosuppressive drugs used to control the disease in 8 patients with BD. The patients were monitored by clinical and ophthalmological examination, as well as extensive immunological investigations. Oral administration of p336–351-CTB had no adverse effect and withdrawal of the immunosuppressive drugs showed no relapse of uveitis in 5 of 8 patients or 5 of 6 selected patients who were free of disease activity prior to initiating the tolerization regimen. After tolerization was discontinued, 3 of 5 patients remained free of relapsing uveitis for 10–18 months after cessation of all treatment. Control of uveitis and extra-ocular manifestations of BD was associated with a lack of peptide-specific CD4+ T cell proliferation, a decrease in expression of TH1 type cells (CCR5, CXCR3), IFN-γ and TNF-α production, CCR7+ T cells and costimulatory molecules (CD40 and CD28), as compared with an increase in these parameters in patients in whom uveitis had relapsed. The efficacy of oral peptide-CTB tolerization will need to be confirmed in a phase III trial, but this novel strategy in humans might be applicable generally to autoimmune diseases in which specific antigens have been identified.
Gastric cancer with metastasis to the gingiva
Authors: SHIMOYAMA SHOUJI , SETO YASUYUKI , AOKI FUMIO , OGAWA TOSHIHISA , TOMA TOSHIYUKI , ENDO HISAKO , ITOUJI TORU , KAMINISHI MICHIO 
Published: June 2004

AbstractThe present case report describes a gastric cancer which showed unusual metastasis in the oral region. A 56‐year‐old male patient underwent total gastrectomy and splenectomy due to advanced gastric cancer in the upper third of the stomach. Fifteen months later, he presented with anorexia and gingival swelling of durations of approximately 3 and 1 month, respectively. The gastric tumor was histologically a signet ring cell and a poorly differentiated cancer with a moderate degree of vascular invasion. Biopsy specimens from the gingival tumor revealed a signet ring cell cancer. Other metastatic sites were the brain, limb bones and abdominal lymph nodes. A bone scintigram revealed an abnormal uptake in the limb bones, while it did not exhibit any abnormality in the oral region. Correlation between the histology of the gingival tumor with that of the gastric cancer, as well as the absence of a gingival tumor at the time of prior gastrectomy, led to a diagnosis that the gingival tumor was a metastasis from gastric cancer. Gastric cancer metastasizing to the oral region, either the osseus or the oral soft tissue, is very rare. Although it cannot be proved without an autopsy, negative findings in the mandible by bone scanning in the present case suggest that direct gingival metastasis can be considered, rather than mandibular metastasis involving the gingiva. Hematogenous spread could be a mechanism of metastasis for this unusual tumor.
Taurocholate transport by hepatic and intestinal bile acid transporters is independent of FIC1 overexpression in Madin–Darby canine kidney cells
Authors: HARRIS MATTHEW J , KAGAWA TATEHIRO , DAWSON PAUL A , ARIAS IRWIN M 
Published: June 2004

AbstractBackground:  Mutations in the human familial intrahepatic cholestasis gene, FIC1, result in progressive familial intrahepatic cholestasis type 1 in children and benign recurrent intrahepatic cholestasis. The present study was performed to determine whether FIC1 transports bile acids and/or influences the activity of apical bile acid transporters.Methods:  The apical secretion assay utilized transfected Madin–Darby canine kidney (MDCK) cells, which stably express the bile acid uptake protein, Na+/taurocholate co‐transporting polypeptide (NTCP). These cells were then transiently transfected with FIC1 and/or the bile salt export pump (BSEP) and were grown on Transwell filters to form a polarized monolayer. [3H]Taurocholate was added to the basal medium and the taurocholate secretion was measured in the apical medium. A second assay, apical uptake assays, utilized polarized MDCK‐II cells, which were transiently transfected with FIC1, FIC1 mutants and/or the apical sodium‐dependent bile acid transporter (ASBT). [3H]Taurocholate was added to the apical media and intracellular uptake of taurocholate was measured.Results:  Apical secretion assays: FIC1 expression in MDCK/NTCP cells had no effect on taurocholate secretion compared to controls. In contrast, apical secretion of taurocholate in BSEP‐transfected cells was approximately twofold higher than in non‐transfected MDCK/NTCP cells (P < 0.01). The BSEP‐mediated secretion was unaffected by co‐transfection with FIC1. Apical uptake assays: taurocholate uptake in ASBT expressing cells was 6.5‐fold higher than in controls and was unaffected by co‐transfection of cells with FIC1 or FIC1 mutants.Conclusions:  These results indicate that FIC1 does not transport taurocholate and, when overexpressed in MDCK cells, had no effect on the function of BSEP or ABST.
Reduced expression of peroxisome proliferator‐activated receptor‐α may have an important role in the development of non‐alcoholic fatty liver disease
Authors: YEON JONG EUN , CHOI KYUNG MOOK , BAIK SEI HYUN , KIM KYOUNG OH , LIM HYOUNG JOON , PARK KI HO , KIM JIN YONG , PARK JONG‐JAE , KIM JAE SEON , BAK YOUNG‐TAE , BYUN KWAN SOO , LEE CHANG HONG 
Published: June 2004

AbstractBackground:  Although the pathogenesis of non‐alcoholic fatty liver disease (NAFLD) remains poorly understood, metabolic syndrome associated with insulin resistance is the most reproducible factor in the development of NAFLD. Fat accumulation in hepatocytes results from an imbalance in the input, output and oxidation of fatty acid. Peroxisomes contain a battery of fatty acid oxidizing enzymes, the first of which, acyl‐CoA oxidase (AOX), initiates the β‐oxidation spiral. One of the mammalian peroxisome proliferator‐activated receptors (PPAR), PPAR‐α, regulates the transcriptional expression of the enzymes involved in fatty acid β‐oxidation. The aim of the present study was to define the role of PPAR‐α and AOX in the development of NAFLD using the Otsuka Long‐Evans Tokushima fatty (OLETF) rat model.Methods:  Liver tissue from OLETF (n = 12) and control (n = 10) rats 12, 28, and 40 weeks old were processed for histopathological and western blot analysis. The messenger RNA of PPAR‐α and AOX were quantified by real‐time RT‐PCR.Results:  At 40 weeks old, the histological analysis of the OLETF rat liver had steatosis (approximately 66%) and mild inflammation, which were comparable to those in NAFLD. Histological changes were unremarkable  in  12 week  and  28 week  rats.  In  12 week  OLETF  rats,  the  mRNA  of  AOX  was  63% of the control. Expression of PPAR‐α mRNA was also reduced to 3% that of the control. Along with the changes of mRNA, the protein expression of PPAR‐α was also significantly reduced to 17% that of the control. In 28 week and 40 week animals, PPAR‐α protein expression gradually increased to 75% and 78% that of the control. Expression of PPAR‐α mRNA was also increased by up to 26% and 110% of the control. AOX, regulated by PPAR‐α, also increased to 149% and 120% of the control.Conclusion:  Reduced expression of PPAR‐α and AOX was observed even before definite steatosis had developed. The alteration of peroxisomal fatty acid metabolism may have an important role in the development of NAFLD.
Preliminary analysis of a newly proposed prognostic scoring system (SLiDe score) for hepatocellular carcinoma
Authors: OMAGARI KATSUHISA , HONDA SUMIHISA , KADOKAWA YOSHIKO , ISOMOTO HAJIME , TAKESHIMA FUMINAO , HAYASHIDA KENJI , MIZUTA YOHEI , MURATA IKUO , KOHNO SHIGERU 
Published: June 2004

AbstractBackground:  The long‐term prognosis of hepatocellular carcinoma (HCC) remains poor and the prediction of survival is often difficult because of the limited liver function and frequent recurrence of HCC in most patients. Therefore, a prognostic classification of HCC should account for both tumor‐related variables and liver function.Methods:  The value of reported prognostic factors for HCC was assessed and a new prognostic classification was established called the ‘SLiDe’ scoring system (S, stage; Li, liver damage; De, des‐γ‐carboxy prothrombin) using ‘stage’ and ‘liver damage’ of the recently revised 4th edition of the Japanese staging system edited by the Liver Cancer Study Group of Japan, and the serum level of des‐γ‐carboxy prothrombin (DCP) in 177 patients with HCC.Results:  Univariate analysis identified Child–Pugh stage, liver damage, tumor morphology, portal vein thrombosis, stage, serum level of α‐fetoprotein (AFP), serum level of DCP, and initial treatment as significant prognostic factors. Of these, liver damage, stage, and serum level of DCP remained independent predictive factors of survival after multivariate prognostic analysis using the proportional hazards regression model. Therefore, a new prognostic scoring system (SLiDe scoring system) was derived that assigned a linear score (0/1/2/3) to these three covariates. This SLiDe scoring system was statistically a better model for predicting outcome in the present study population than the Cancer of the Liver Italian Program (CLIP) and the Japan Integrated Staging (JIS) scoring systems, as judged by the Akaike Information Criteria.Conclusion:  The SLiDe scoring system is useful for the assessment of the prognosis of patients with HCC as long as the Japanese staging system is used, although this uses parameters such as the indocyanine green retention test and DCP, which are not examined routinely in every part of the world. Therefore, the proposed classification should be further validated in other large study populations.© 2004 Blackwell Publishing Asia Pty Ltd
Efficacy of transanal endoscopic microsurgery in the management of rectal polyps
Authors: PLATELL CAMERON , DENHOLM EVA , MAKIN GREGORY 
Published: June 2004

AbstractBackground and Aim:  Transanal endoscopic microsurgery (TEM) was a technique developed to allow the excision of adenomas and early‐stage cancers from the rectum and distal sigmoid colon. The aim of this project was to prospectively study surgical morbidity, mortality and the local recurrence rate of all patients treated with this technique.Methods:  All patients undergoing TEM were prospectively evaluated. Endpoints to assess the surgical morbidity and mortality were defined before the study commenced. All patients underwent regular follow up to determine treatment efficacy in terms of the local recurrence rate and survival.Results:  The study involved 113 patients, with a mean age of 69 years (standard deviation 14 years, range 30–94 years), and a male to female ratio of 1.4:1. The mean polyp area was 20.5 cm2 (range 1–169 cm2) and the mean height above the anal verge was 9.5 cm (range 4–25 cm). Histology of the tumors found 62 adenomas, 20 carcinomas in situ, and 31 adenocarcinomas. There were no unplanned returns to theater or postoperative deaths. Four patients required readmission within 30 days because of bleeding, and nine patients underwent more radical surgical procedures following histological evaluation of the resected specimens. During a mean follow up of 1.5 ± 0.8 years (maximum 3.2 years), there have been two recurrences of villous adenomas. The actuarial local recurrence rate at 2 years is 2.4% (95% confidence interval 0.8–4.0%).Conclusion:  TEM was demonstrated to be a safe surgical procedure, and early follow up has shown it to be an efficacious treatment for benign rectal adenomas and early rectal cancers.© 2004 Blackwell Publishing Asia Pty Ltd
Chromosomal and microsatellite instability in sporadic gastric cancer
Authors: HIYAMA TORU , TANAKA SHINJI , YOSHIHARA MASAHARU , SASAO SHOGO , KOSE KAZUHIRO , SHIMA HIDEYUKI , TUNCEL HANDAN , UENO YOSHITAKA , ITO MASANORI , KITADAI YASUHIKO , YASUI WATARU , HARUMA KEN , CHAYAMA KAZUAKI 
Published: June 2004

AbstractBackground:  Gastric cancer can progress through two pathways of genomic instability: chromosomal (CIN) and microsatellite instability (MSI). It is hypothesized that these two pathways are not always independent and that some tumors show overlap between these two mechanisms.Methods:  A total of 98 sporadic gastric cancers were classified based on their MSI status, using microsatellite assay with BAT26. Evidence for CIN was investigated by identifying loss of heterozygosity (LOH) events on chromosome arms, 5q, 10p, 17p, 17q, and 18q, which are regions harboring tumor suppressor genes that are significant in gastric cancer development.Results:  Twelve tumors (12%) showed high‐frequency MSI (MSI‐H). Overall, 43 of the tumors (44%) had at least one LOH event, with most frequent chromosomal losses observed on 10p and 18q (30%, respectively), followed by 5q (21%), 17p (14%), and 17q (12%). Interestingly, overlap was observed between CIN and MSI pathways. Of 43 cancers with LOH events, four (9%) were also MSI‐H. It was also found that 48% of cancers without MSI‐H had no LOH events identified, comprising a subgroup of tumors that were not representative of either of these two pathways of genomic instability.Conclusion:  These results suggest that molecular mechanisms of genomic instability are not necessarily independent and may not be fully defined by either the MSI or CIN pathways in sporadic gastric cancers.
Cisapride treatment of constipation–predominant irritable bowel syndrome is not superior to placebo
Authors: ZIEGENHAGEN DIETER J , KRUIS WOLFGANG 
Published: June 2004

AbstractBackground and Aim:  Previous studies with cisapride reported conflicting results in patients with constipation–predominant irritable bowel syndrome (IBS). To gain further evidence, this randomized double‐blind study was carried out.Methods:  Eighty‐two symptomatic outpatients were randomized to receive either 5 mg oral cisapride or placebo three times daily for a period of 12 weeks. In patients without satisfactory improvement after 4 weeks, the dose was doubled. Symptom evaluation used visual analog scales (VAS) and the investigators’ global assessment.Results:  After 4 weeks, in 18 (45%) cisapride and 24 (57%) placebo patients the dose was doubled because of insufficient improvement of symptoms. The mean VAS score for patients’ global rating of IBS symptoms at baseline was 67.5 mm for cisapride versus 70.7 mm for placebo, and improved to 38.4 mm versus 44.5 mm after 12 weeks of treatment. Investigators rated the overall effect of therapy as good or excellent in 70% of the cisapride and 50% of the placebo group. Neither these nor further efficacy parameter differences reached statistical significance.Conclusions:  These results indicate that the effect of 15–30 mg cisapride daily on symptoms of constipation‐predominant IBS is not significantly superior to placebo. During the 12 week treatment of this trial cisapride proved to be safe and tolerable.
Differentiation of cystic pancreatic neoplasms and pseudocysts by conventional and echo‐enhanced ultrasound
Authors: RICKES STEFFEN , WERMKE WOLFRAM 
Published: June 2004

AbstractBackground and Aims:  Echo‐enhanced sonography is a non‐invasive and increasingly used procedure for the differentiation of pancreatic tumors. However, the diagnostic accuracy of this procedure compared to conventional ultrasound for the differential diagnosis of cystic pancreatic neoplasms from pseudocysts has never been investigated in a prospective study.Methods:  Thirty‐one patients with a cystic pancreatic lesion at the conventional ultrasound (mean age 57 years, range 36–82 years) were included in the study. Sonography was performed by an experienced examiner who was unaware of the patients’ clinical diagnosis. The exact diagnosis was based on histological evidence from biopsy examination (surgical or transabdominal fine needle biopsy for all cystic neoplasms and five pseudocysts), or a follow‐up of at least 18 months (four pseudocysts).Results:  Of the 31 patients, 19 had cystadenomas, three had cystadenocarcinomas, and nine had pseudocysts. Only 27% of the cystadenomas and 67% of the pseudocysts could be correctly classified by conventional ultrasound. Conversely, 95% of the cystadenomas (P = 0.0001) and all pseudocysts were diagnosed correctly by echo‐enhanced sonography. The sensitivity of echo‐enhanced sonography with respect to diagnosing cystadenoma was 95% and its specificity was 92%. The corresponding values for pseudocysts were both 100%.Conclusion:  Echo‐enhanced sonography has a high sensitivity and specificity in the differential diagnosis of cystic pancreatic tumors. With this procedure the differentiation of cystadenomas and pseudocysts can be improved. However, histology is the standard of reference.
Hepatitis E virus infection may be transmitted through blood transfusions in an endemic area
Authors: KHUROO MOHAMMAD SULTAN , KAMILI SALEEM , YATTOO GHULAM NABI 
Published: June 2004

AbstractAim:  To address the issue of whether or not hepatitis E virus (HEV) is transmitted parenterally.Methods:  We conducted a retrospective study which involved 145 multiple transfused patients and 250 healthy controls. A prospective study was also undertaken involving 50 hospitalized patients, 25 of whom were transfused with 107 blood units, while the other 25 did not receive any transfusions.Results:  In our retrospective study, markers of acute HEV infection (IgM anti‐HEV and HEV RNA) were detected in a significantly higher number of multiple transfused patients (13 of 145) compared to controls (two of 250) (P < 0.001; OR = 12.21 [95% confidence interval: 2.71–54.70]). All 13 HEV‐infected patients had been transfused at least once in a 3‐month period before testing. Overall, patients positive for any of the HEV markers (IgG, IgM or HEV RNA) had received more blood transfusions, had higher occurrence of icteric disease and higher serum alanine aminotransferase levels. In our prospective study, IgG anti‐HEV was detected in 11 of 107 donor samples, three of 25 patients in their pretransfusion samples (one sample was positive for IgM anti‐HEV as well) and two of 25 control patients. Post‐transfusion HEV infection developed in three of 22 susceptible (IgG anti‐HEV negative) transfused patients; the infection was traced to their four respective donors who were asymptomatic, HEV RNA positive (4/4) and IgM anti‐HEV positive (3/4). In contrast, none of the non‐transfused patients developed HEV infection during the follow‐up period.Conclusion:  Frequent transmission of HEV by blood transfusion places recipients at risk and warrants redefining of the donor screening policy by blood banks, especially in endemic areas.
Internal loading: A new solution to an old problem in aquatic sciences
Authors: Håkanson Lars 
Published: June 2004

AbstractInternal loading has long been regarded as an ‘Achilles heel’ in aquatic science and management. Internal loading is of fundamental importance in large and shallow lakes, where even low wind velocities can cause a considerable resuspension of matter deposited on the lake bed. The resuspended matter, and the chemical substances bound to the resuspended matter, will influence almost all processes in the aquatic ecosystem, such as water clarity and depth of the photic zone, and hence, primary and secondary production. If the sediments are contaminated, it will increase the concentrations of harmful substances in water and sediments and the potential ecosystem effects related to such concentrations. This paper presents an overview of the processes regulating bottom dynamic conditions in lakes (erosion, transport, accumulation), provides examples on the role of internal loading within the context of limnology and water management, and presents a new, general approach to quantify internal loading from sediments in lakes. The new approach has been critically tested, being a key factor behind the increase in predictive power of a new generation of lake models meant to be used for practical water management. Internal loading of any water pollutant depends on sedimentation. Sedimentation in this approach is presented as a function of two substance‐specific variables, including the fall velocity of the carrier‐particles and the particulate fraction (which, by definition, is the only fraction of a water pollutant that can settle out on the lake bed), and three generic variables, including mean depth, suspended particulate matter and ET‐areas (areas of erosion and transport). On ET‐areas there is, by definition, a discontinuous sedimentation of materials that settles according to Stokes' law. Basically, internal loading is the sum of advective (resuspension) and diffusive transport from the sediments. Resuspension from ET‐areas is given as a function of the lake form (a new algorithm based on the volume development) and the age of ET‐sediments.