bluuebunny/crossref_metadata_2025 huggingface dataset:
PDE1B2 regulates cGMP and a subset of the phenotypic characteristics acquired upon macrophage differentiation from a monocyte
Authors: Bender Andrew T. , Beavo Joseph A.
Published: January 2006

Monocyte-to-macrophage differentiation with the cytokine granulocyte–macrophage colony-stimulating factor induces expression of the cyclic nucleotide phosphodiesterase PDE1B2. However, what role PDE1B2 plays in macrophage biology has not been elucidated. We have addressed this question by inhibiting PDE1B2 induction by using RNA interference. Using a retrovirus-based system, we created HL-60 stable cell lines that express a short-hairpin RNA targeting PDE1B2. HL-60 cells treated with phorbol-12-myristate-13-acetate differentiate to a macrophage-like phenotype and up-regulate PDE1B2. However, expression of PDE1B2 short hairpin RNA effectively suppresses PDE1B2 mRNA, protein, and activity up-regulation. Using the HL-60 PDE1B2 knockdown cells and agonists for either adenylyl or guanylyl cyclase, it was found that PDE1B2 predominantly regulates cGMP and plays a lesser role in cAMP regulation in response to cyclase agonists. Furthermore, in intact HL-60 cells, PDE1B2 activity can be regulated by changes in Ca+2levels. Inhibiting PDE1B2 up-regulation does not prevent HL-60 cell differentiation, because several markers of macrophage differentiation are unaffected. However, suppression of PDE1B2 expression alters some aspects of the macrophage-like phenotype, because cell spreading, phagocytic ability, and CD11b expression are augmented. The cAMP analog 8-Bromo-cAMP reverses the changes caused by PDE1B2 knockdown. Also, PDE1B2 knockdown cells have lower basal levels of cAMP and alterations in the phosphorylation state of several probable PKA substrate proteins. Thus, the effects of PDE1B2 on differentiation may ultimately be mediated through decreased cAMP. In conclusion, PDE1B2 regulates a subset of phenotypic changes that occur upon phorbol-12-myristate-13-acetate-induced differentiation and likely also plays a role in differentiated macrophages by regulating agonist-stimulated cGMP levels.
Tissue Bioenergetics and Microvascular Perfusion Are Impaired in Rat Ileal Mucosa in Normotensive Sepsis
Authors: ROSE JIM , MARTIN CLAUDIO
Published: January 2006

Objective: Sepsis is a systemic inflammatory response to a bacterial infection. Inflammation may result in injury to the small bowel and an increase in translocation of bacteria and toxins across the mucosal barrier, which may contribute to the progression of sepsis. Microcirculatory perfusion or cytopathic hypoxia may cause impairment of tissue bioenergetics and injury in sepsis. The objective of this study was to determine if sepsis is associated with microcirculatory hypoperfusion and impaired tissue bioenergetics in the ileal mucosa.

Materials and Methods: Sprague‐Dawley rats were randomized to cecal ligation and perforation (sepsis group, n = 12) or control group (n = 14) and received arterial and venous catheters and fluid resuscitation. Following 24 h, rats were anesthetized with isoflurane and the ileum was prepared for intravital microscopy. Images of NADH fluorescence, which is an index of tissue bioenergetics, central arterial diameter, red cell velocity, red cell flux, and average intercapillary area, were recorded in 6–9 villi in each rat.

Results: Central arterial red cell flux (control 277 ± 30 cell/s, sepsis 108 ± 13 cells/s, p < .05), diameter (control 10.4 ± 0.4 μ m, sepsis 8.2 ± 0.3 μ m, p < .05) and red cell velocity (control 590 ± 47 μ m/s, sepsis 449 ± 63 μ m/s, p < .05) were decreased while average intercapillary area (control 815 ± 171 μ m2, sepsis 1412 ± 364 μ m2, p < .05) and NADH fluorescence (control 116 ± 6 AIU, sepsis 154 ± 9 AIU, p < .05) were increased at the villus tip in the sepsis group.

Conclusion: Sepsis is associated with bioenergetic impairment and capillary hypoperfusion at the villus tip and a decrease in red cell flux in the central arteriole.
Genotoxicity Assessment of Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)
Authors: Reddy Gunda , Erexson Gregory L. , Cifone Maria A. , Major Michael A. , Leach Glenn J.
Published: January 2006

Hexahydro-1,3,5-trinitro-1,3,5-triazine, a polynitramine compound, commonly known as RDX, has been used as an explosive in military munitions formulations since World War II. There is considerable data available regarding the toxicity and carcinogenicity of RDX. It has been classified as a possible carcinogen (U.S. Environmental Protection Agency, Integrated Risk Information System, 2005, www.epa.gov/IRIS/subst/0313.htm ). In order to better understand its gentoxic potential, the authors conducted the in vitro mouse lymphoma forward mutation and the in vivo mouse bone marrow micronucleus assays. Pure RDX (99.99%) at concentrations ranging from 3.93 to 500 μg/ml showed no cytotoxicity and no mutagenicity in forward mutations at the thymidine kinase (TK) locus in L5178Y mouse lymphoma cells, with and without metabolic activation. This finding was also confirmed by repeat assays under identical conditions. In addition, RDX did not induce micronuclei in mouse bone marrow cells when tested to the maximum tolerated dose of 250 mg/kg in male mice. These results show that RDX was not mutagenic in these in vitro and in vivo mammalian systems.
Identification of the target self-antigens in reperfusion injury
Authors: Zhang Ming , Alicot Elisabeth M. , Chiu Isaac , Li Jinan , Verna Nicola , Vorup-Jensen Thomas , Kessler Benedikt , Shimaoka Motomu , Chan Rodney , Friend Daniel , Mahmood Umar , Weissleder Ralph , Moore Francis D. , Carroll Michael C.
Published: January 2006

Reperfusion injury (RI), a potential life-threatening disorder, represents an acute inflammatory response after periods of ischemia resulting from myocardial infarction, stroke, surgery, or trauma. The recent identification of a monoclonal natural IgM that initiates RI led to the identification of nonmuscle myosin heavy chain type II A and C as the self-targets in two different tissues. These results identify a novel pathway in which the innate response to a highly conserved self-antigen expressed as a result of hypoxic stress results in tissue destruction.
Antiidiotypic DNA vaccination induces serum bactericidal activity and protection against group B meningococci
Authors: Beninati Concetta , Midiri Angelina , Mancuso Giuseppe , Biondo Carmelo , Arigò Milena , Gerace Elisabetta , Papasergi Salvatore , Gambuzza Maria , Boretti Mauro , Magliani Walter , Conti Stefania , Polonelli Luciano , Teti Giuseppe
Published: January 2006

No vaccine is available for preventing infections by serogroup B Neisseria meningitidis (MenB), which accounts for a major portion of meningococcal cases in developed countries, because of the poor immunogenicity of the capsular polysaccharide (CP) even after protein conjugation. We have previously induced anticapsular antibodies by immunization with a single chain variable fragment (scFv), which mimics a protective CP epitope. This surrogate antigen, however, was ineffective at inducing serum bactericidal activity, an accepted marker of protection in humans. Serum bactericidal activity was consistently achieved by immunizing mice with the scFv-encoding gene. Immunization with vectors without a secretory signal sequence before the scFv resulted in markedly higher bactericidal activity relative to those with such a sequence. The induced antibodies were capsule specific, as shown by complete inhibition of bactericidal activity by purified MenB CP and by resistance to killing of MenA or MenC. Moreover, these antibodies were predominantly of the IgG2a isotype, reflecting a T helper type 1 response. Administration of sera from scFv gene–vaccinated animals protected infant rats against MenB bacteremia. These data illustrate the potential of vaccination with genes encoding capsular mimics in providing protection against MenB and other encapsulated bacteria.
Educational outcomes of a workplace screening program for genetic susceptibility to hemochromatosis
Authors: Nisselle AE , Collins VR , Gason AA , Flouris A , Delatycki MB , Allen KJ , Aitken MA , Metcalfe SA
Published: January 2006

Education is an essential component of a genetic screening program. Knowledge outcomes were measured after large‐scale workplace education and screening for genetic susceptibility to hereditary hemochromatosis. The aim was to assess knowledge of concepts presented, impact of mode of delivery, and knowledge retention. Education in a group setting was delivered via oral or video presentation and knowledge assessed using self‐administered questionnaires at baseline, 1 month, and 12 months. Over 60% of 11 679 participants correctly answered all questions at baseline, scoring higher with clinical concepts (disease etiology and treatment) than genetic concepts (penetrance and genetic heterogeneity). Revising the education program significantly increased correct responses for etiology (p < 0.002), whilst modifying the knowledge assessment tool significantly increased correct responses for etiology (p < 0.001) and gene penetrance (p < 0.001). For three of the four concepts assessed, use of video was as effective as oral presentation for knowledge outcomes. A significantly higher proportion of those at increased risk of disease (n = 44) responded correctly at 12 months than did controls (n = 82; p = 0.011 for etiology, p = 0.002 for treatment and p = 0.003 for penetrance). Hence, genetic screening can be successfully offered in a group workplace setting, with participants remembering clinical concepts better than genetic concepts up to 1 year later.
Predicting Nursing Facility Residents' Quality of Life Using External Indicators
Authors: Degenholtz Howard B. , Kane Rosalie A. , Kane Robert L. , Bershadsky Boris , Kling Kristen C.
Published: January 2006

Purpose. A newly developed brief measure of nursing facility (NF) resident self‐reported quality of life (QOL) has been proposed for inclusion in a modified version of the minimum data set (MDS). There is considerable interest in determining whether it is possible to develop indicators of QOL that are more convenient and less expensive than direct, in‐person interviews with residents.

Design and Methods. QOL interview data from 2,829 residents living in 101 NFs using a 14‐item version of a longer instrument were merged with data from the MDS and the Online Survey and Certification Automated Record (OSCAR). Bivariate and multivariate hierarchical linear modeling were used to assess the association of QOL with potential resident and facility level indicators.

Results. Resident and facility level indicators were associated with self‐reported QOL in the expected direction. At the individual resident level, QOL is negatively associated with physical function, visual acuity, continence, being bedfast, depression, conflict in relationships, and positively associated with social engagement. At the facility level, QOL is negatively associated with citations for failing to accommodate resident needs or providing a clean, safe environment. The ratio of activities staff to residents is positively associated with QOL. This study did not find an association between QOL and either use of restraints or nurse staff levels. Approximately 9 percent of the total variance in self‐reported QOL can be attributed to differences among facilities; 91 percent can be attributed to differences among residents. Resident level indicators explained about 4 percent of the variance attributable to differences among residents, and facility factors explained 49 percent of the variance attributable to differences among NFs. However, the different variables explained only 10 percent of the variance in self‐reported QOL.

Implications. A brief self‐report measure of NF resident QOL is consistently associated with measures that can be constructed from extant data sources. However, the level of prediction possible from these data sources does not justify reliance on external indicators of resident QOL for policy purposes.
Should Episode‐Based Economic Profiles Be Risk Adjusted to Account for Differences in Patients' Health Risks?
Authors: Thomas J. William
Published: January 2006

Objective. To determine whether additional risk adjustment is necessary in economic profiling of physicians when claims data are already grouped into episodes of care, and to measure effects of risk adjustment on cost efficiency rankings of physicians.

Data Sources. Four years of inpatient, outpatient, professional, and pharmacy claims data from a mixed model HMO.

Study Design. Claims data were processed through Symmetry Health Data Systems' episode treatment group (ETG) grouper to define episodes of care and Symmetry's episode risk group (ERG) software to define measures of patients' health risk scores. For each episode type (ETG), ETG‐mean expected costs were calculated as the mean costs of all episodes of that type, and risk‐adjusted expected costs were calculated using three alternative risk model formulations.

Data Collection. Within specialties, physicians were ranked from most cost efficient to least cost efficient, based on standardized difference between actual and expected costs. ETG‐mean based rankings were compared with risk‐adjusted rankings. Analyses were performed for cardiologists, family practitioners, general surgeons, and neurologists.

Principal Findings. With all three risk models, risk scores were essentially unrelated to episode costs in approximately three‐fourths of episode categories (ETGs). In a sample of ETGs for which risks–costs relationships appeared to exist, split sample validation showed the relationships to be unstable or spurious in all except one ETG. Within specialties, risk‐adjusted cost efficiency rankings differ little from ETG‐mean adjusted rankings.

Conclusions. Depending upon the purpose for which economic profiling is performed, additional risk adjustment, beyond that already provided by episode grouping, may be unnecessary. Additional research may be needed to identify and validate ETG‐level relationships between patient risks and episode costs.
Redescription of Lagenophrys cochinensis Santhakumari & Gopalan, 1980 (Ciliophora, Peritrichia, Lagenophryidae), an Ectosymbiont of Marine Isopods, Including New Information on Morphology, Geographic Distribution, and Intraspecific Variation
Authors: CLAMP JOHN C.
Published: January 2006

ABSTRACT. Lagenophrys cochinensis is a peritrich ciliate originally reported as an ectocommensal of the wood‐boring isopods Sphaeroma terebrans, Sphaeroma triste, and Sphaeroma annandalei and the tanaidacean Apseudes chilkensis in estuaries of southern India. In the present study, it was found to occur also on Sphaeroma quoyanum, Sphaeroma walkeri, and Exosphaeroma planulum. New material was used to make permanent preparations, allowing a comprehensive description of the morphology of L. cochinensis for the first time. The macronucleus of L. cochinensis was found to have an elongate shape that spans the width of the cell body, unlike the compact macronucleus originally described. In addition, the loricae of all samples examined were subcircular or shorter than wide, not longer than wide as originally described. Polykinetid 3 of the infundibular infraciliature consisted of three rows of kinetosomes, only the third species of Lagenophrys found to have more than two rows in polykinetid 3 so far. Samples of L. cochinensis on S. quoyanum from New Zealand and California appeared to represent a population distinct from others. The species has a cosmopolitan distribution, probably owing to the ease with which its hosts are transported from one estuary to another in drifting wood or on hulls of ships.
Displacement‐based binning of time‐dependent computed tomography image data sets
Authors: Fitzpatrick Mathew J. , Starkschall George , Antolak John A. , Fu Jun , Shukla Himanshu , Keall Paul J. , Klahr Paul , Mohan Radhe
Published: January 2006

Respiration can cause tumors in the thorax or abdomen to move by as much as ; this movement can adversely affect the planning and delivery of radiation treatment. Several techniques have been used to compensate for respiratory motion, but all have shortcomings. Manufacturers of computed tomography (CT) equipment have recently used a technique developed for cardiac CT imaging to track respiratory‐induced anatomical motion and to sort images according to the phase of the respiratory cycle they represent. Here we propose a method of generating CT images that accounts for respiratory‐induced anatomical motion on the basis of displacement, i.e., displacement‐binned CT image sets. This technique has shown great promise, however, it is not fully supported by currently used CT image reconstruction software. As an interim solution, we have developed a method for extracting displacement‐binned CT image data sets from data sets assembled on the basis of a prospectively determined breathing phase acquired on a multislice helical CT scanner. First, the projection data set acquired from the CT scanner was binned at small phase intervals before reconstruction. The manufacturer's software then generated image sets identified as belonging to particular phases of the respiratory cycle. All images were then individually correlated to the displacement of an external fiducial marker. Next, CT image data sets were resorted on the basis of the displacement and assigned an appropriate phase. Finally, displacement‐binned image data sets were transferred to a treatment‐planning system for analysis. Although the technique is currently limited by the phase intervals allowed by the CT software, some improvement in image reconstruction was seen, indicating that this technique is useful at least as an interim measure.
Technique for routine output verification of Leipzig applicators with a well chamber
Authors: Pérez‐Calatayud J. , Granero D. , Ballester F. , Crispín V. , van der Laarse R.
Published: January 2006

The H‐type Leipzig applicators are accessories of the microSelectron‐HDR system (Nucletron, Veenendaal, The Netherlands) for treatment of superficial malignancies. Recently, the dose rate distributions in liquid water for the whole set of applicators using both source models available for the microSelectron‐HDR afterloaders have been obtained by means of the experimentally validated Monte Carlo (MC) code GEANT4. Also an output table (cGy/hU) at depth on the applicator central axis was provided. The output verification of these applicators by the user, prior to their clinical use, present practical problems: small detectors such as thermoluminescent dosimeters or parallel‐plate ionization chambers are not easily used for verification in a clinical environment as they require a rigid setup with the Leipzig applicator and a phantom. In contrast, well‐type ionization chambers are readily available in radiotherapy departments. This study presents a technique based on the HDR1000Plus well chamber (Standar Imaging) measurements with a special insert, which allows the output verification of the H‐type Leipzig applicators on a routine basis. This technique defines correspondence factors (CF) between the in water dose rate output of the Leipzig applicators (cGy/hU) obtained with MC and the reading on the well chamber with the special insert, normalized to the HDR calibration factor with the HDR insert and to the source strength. To commission the applicators (with the well chamber and the special insert used), the physicist should check if the CF value agrees with its tabulated values presented in this work. If the differences are within 5% the tabulated output values can be used in clinical dosimetry. This technique allows the output validation of the Leipzig applicators with a well chamber widely used for HDR Ir‐192 source strength measurements. It can easily be adapted to other types of well chambers for HDR source output verification.
Measurement accuracy and Cerenkov removal for high performance, high spatial resolution scintillation dosimetry
Authors: Archambault Louis , Beddar A. Sam , Gingras Luc , Roy René , Beaulieu Luc
Published: January 2006

With highly conformal radiation therapy techniques such as intensity‐modulated radiation therapy, radiosurgery, and tomotherapy becoming more common in clinical practice, the use of these narrow beams requires a higher level of precision in quality assurance and dosimetry. Plastic scintillators with their water equivalence, energy independence, and dose rate linearity have been shown to possess excellent qualities that suit the most complex and demanding radiation therapy treatment plans. The primary disadvantage of plastic scintillators is the presence of Cerenkov radiation generated in the light guide, which results in an undesired stem effect. Several techniques have been proposed to minimize this effect. In this study, we compared three such techniques—background subtraction, simple filtering, and chromatic removal—in terms of reproducibility and dose accuracy as gauges of their ability to remove the Cerenkov stem effect from the dose signal. The dosimeter used in this study comprised a plastic scintillating fiber probe, an optical fiber, and a color charge‐coupled device camera. The whole system was shown to be linear and the total light collected by the camera was reproducible to within 0.31% for integration time. Background subtraction and chromatic removal were both found to be suitable for precise dose evaluation, with average absolute dose discrepancies of 0.52% and 0.67%, respectively, from ion chamber values. Background subtraction required two optical fibers, but chromatic removal used only one, thereby preventing possible measurement artifacts when a strong dose gradient was perpendicular to the optical fiber. Our findings showed that a plastic scintillation dosimeter could be made free of the effect of Cerenkov radiation.
Multiparametric fit method in reconstruction of Fletcher‐Suit‐Delclos applicator
Authors: Palvolgyi Jeno
Published: January 2006

In our institution we have introduced the variable angle reconstruction method with a nonisocentric C‐arm as brachytherapy localizer in gynecological treatments. The main advantage of this method is that on the posterior oblique images the ovoids of the Fletcher‐Suit‐Delclos (FSD) applicator are clearly separated. The main problem with the nonisocentric machine is that the magnification factor is not known exactly and varies with the C‐arm angle. For generation of treatment plans with a commercial brachytherapy planning system the magnification factors of the reconstruction images have to be determined previously. We present a multiparametric fit method (MPF) that is suitable for reconstruction of FSD applicators and that utilizes pairs of posterior‐anterior and lateral or preferably posterior oblique reconstruction images obtained by a C‐arm. The MPF reconstruction relies on the known geometry of the tandem and the ovoid. The actual FSD insertion is reconstructed by adaptation of the geometry of tandem and ovoid by translations and rotations. The fixation mechanism limits the possible excursions of the FSD applicator's parts. The limited freedom of excursions and the determination of the magnification factors are also incorporated.
Projection profile analysis for automated detection of abnormalities in chest radiographs
Authors: Kao E‐Fong , Lee Chungnan , Hsu Jui‐Sheng , Jaw Twei‐Shiun , Liu Gin‐Chung
Published: January 2006

Abnormalities in chest images often present as abnormal opacity or abnormal asymmetry. We have developed a novel method for automated detection of abnormalities in chest radiographs by use of these features. Our method is based on an analysis of the projection profile obtained by projecting the pixels data of a frontal chest image on to the mediolateral axis. Two indices, lung opacity index and lung symmetry index, are computed from the projection profile. Lung opacity index and lung symmetry index are then combined to detect gross abnormalities in chest radiographs. The values of lung opacity index are found to be and for normal right and left lung, respectively. The values of lung symmetry index are found to be for normal chest images. The discrimination for the combination of the two indices is evaluated by linear discriminant analysis and receiver operating characteristic (ROC) analysis. Area under the ROC curve with the combination of the two indices in the classification of normal and abnormal chest images is 0.963.
Gadolinium neutron capture brachytherapy (GdNCB), a new treatment method for intravascular brachytherapy
Authors: Enger Shirin A. , Rezaei Arash , Munck af Rosenschöld Per , Lundqvist Hans
Published: January 2006

Restenosis is a major problem after balloon angioplasty and stent implantation. The aim of this study is to introduce gadolinium neutron capture brachytherapy (GdNCB) as a suitable modality for treatment of stenosis. The utility of GdNCB in intravascular brachytherapy (IVBT) of stent stenosis is investigated by using the GEANT4 and MCNP4B Monte Carlo radiation transport codes. To study capture rate, Kerma, absorbed dose and absorbed dose rate around a Gd‐containing stent activated with neutrons, a long, diameter gadolinium foil is chosen. The input data is a neutron spectrum used for clinical neutron capture therapy in Studsvik, Sweden. Thermal neutron capture in gadolinium yields a spectrum of high‐energy gamma photons, which due to the build‐up effect gives an almost flat dose delivery pattern to the first around the stent. The absorbed dose rate is , from the stent surface while the dose to normal tissue is in order of , i.e., a factor of 6 lower. To spare normal tissue further fractionation of the dose is also possible. The capture rate is relatively high at both ends of the foil. The dose distribution from gamma and charge particle radiation at the edges and inside the stent contributes to a nonuniform dose distribution. This will lead to higher doses to the surrounding tissue and may prevent stent edge and in‐stent restenosis. The position of the stent can be verified and corrected by the treatment plan prior to activation. Activation of the stent by an external neutron field can be performed days after catherization when the target cells start to proliferate and can be expected to be more radiation sensitive. Another advantage of the nonradioactive gadolinium stent is the possibility to avoid radiation hazard to personnel.
A simple, direct method for x‐ray scatter estimation and correction in digital radiography and cone‐beam CT
Authors: Siewerdsen J. H. , Daly M. J. , Bakhtiar B. , Moseley D. J. , Richard S. , Keller H. , Jaffray D. A.
Published: January 2006

X‐ray scatter poses a significant limitation to image quality in cone‐beam CT (CBCT), resulting in contrast reduction, image artifacts, and lack of CT number accuracy. We report the performance of a simple scatter correction method in which scatter fluence is estimated directly in each projection from pixel values near the edge of the detector behind the collimator leaves. The algorithm operates on the simple assumption that signal in the collimator shadow is attributable to x‐ray scatter, and the 2D scatter fluence is estimated by interpolating between pixel values measured along the top and bottom edges of the detector behind the collimator leaves. The resulting scatter fluence estimate is subtracted from each projection to yield an estimate of the primary‐only images for CBCT reconstruction. Performance was investigated in phantom experiments on an experimental CBCT benchtop, and the effect on image quality was demonstrated in patient images (head, abdomen, and pelvis sites) obtained on a preclinical system for CBCT‐guided radiation therapy. The algorithm provides significant reduction in scatter artifacts without compromise in contrast‐to‐noise ratio (CNR). For example, in a head phantom, cupping artifact was essentially eliminated, CT number accuracy was restored to within 3%, and CNR (breast‐to‐water) was improved by up to 50%. Similarly in a body phantom, cupping artifact was reduced by at least a factor of 2 without loss in CNR. Patient images demonstrate significantly increased uniformity, accuracy, and contrast, with an overall improvement in image quality in all sites investigated. Qualitative evaluation illustrates that soft‐tissue structures that are otherwise undetectable are clearly delineated in scatter‐corrected reconstructions. Since scatter is estimated directly in each projection, the algorithm is robust with respect to system geometry, patient size and heterogeneity, patient motion, etc. Operating without prior information, analytical modeling, or Monte Carlo, the technique is easily incorporated as a preprocessing step in CBCT reconstruction to provide significant scatter reduction.
The ECM proteoglycan decorin links desmoplasia and inflammation in chronic pancreatitis
Authors: Köninger J , Giese N A , Bartel M , di Mola F F , Berberat P O , di Sebastiano P , Giese T , Büchler M W , Friess H
Published: January 2006

Background:Recurrent inflammation in chronic pancreatitis (CP) is not well understood.

Aims:To investigate whether decorin, an extracellular matrix (ECM) proteoglycan with macrophage modulating activity, is a pathogenic factor allowing diseased pancreatic stroma to sustain inflammation by affecting the cytokine profile of accumulating inflammatory cells.

Methods:Decorin was examined in 18 donors and 32 patients with CP by quantitative reverse transcription polymerase chain reaction (QRT-PCR), western blotting, and immunohistochemistry of pancreatic specimens. QRT-PCR was used to assess cytokine expression in donor peripheral blood mononuclear cells (PBMC), exposed or not to decorin in vitro, and to compare it with the cytokine profile of circulating and resident mononuclear cells (MNC) of patients with CP.

Results:In CP, desmoplasia is associated with overexpression of decorin in the growing ECM and enlarged pancreatic nerves. In culture, exposure of MNC to decorin stimulated expression of the MNC recruiting chemokine MCP-1. In biopsies, MNC infiltrates in decorin rich CP tissue showed a 300-fold upregulation of MCP-1 compared with decorin free peripheral blood, whereas no difference was found in basal MCP-1 expression in PBMC of patients versus donors. This effect was specific for MCP1—other inflammatory cytokines, such as interleukin 1β and tumour necrosis factor α, were not affected.

Conclusion:Decorin is a molecular marker of desmoplasia in CP, and excessive decorin may allow fibrotic masses to nourish and protract inflammation by deregulating the process of MNC accumulation and activation. These data provide a molecular basis for surgical resection of diseased tissue as a treatment option in CP.
Morules and morule-like features associated with carcinomas in various organs: report with immunohistochemical and molecular studies
Authors: Makishi S , Kinjo T , Sawada S , Chinen K , Hirayasu T , Hamada T , Saito K , Iwamasa T
Published: January 2006

Background:Morules have been reported in pulmonary blastoma (PB), well differentiated fetal adenocarcinoma of the lung (WDFA), and uterine endometrioid carcinoma (EC), and rarely in other carcinomas. β Catenin gene mutation has been associated with morule formation.

Aims:To compare and clarify the cellular characteristics of morules in carcinomas in various organs and show that morules are distinct from epithelial cellular nodules.

Methods:Twenty tumours were studied: two PBs, three WDFAs, three papillary lung adenocarcinomas, 11 ECs, and one papillary thyroid carcinoma. Numerous epithelial cell, oncofetal, and neuropeptide antibodies were used for immunohistochemistry. β Catenin gene mutation was investigated.

Results:Morules in PBs and ECs were uniform cell clusters distinct from squamous differentiation. All were immunonegative for epithelial cell and oncofetal antigens, but those in ECs were positive for neurone specific enolase γ (NSEγ). Synaptophysin, encephalin, and somatostatin were sporadically immunopositive in PB morules. Morules were not seen in the other carcinomas and WDFAs, although morule-like features closely resembling morules histopathologically were seen. These were positive for epithelial cell and oncofetal antigens, and showed squamous differentiation. Their nuclei were more atypical and slightly larger than those in morules. Morule-like features were seen in WDFAs. β Catenin gene mutation was demonstrated in one EC and PB, and in two WDFAs.

Conclusion:Morules were non-epithelial cell clusters showing neuronal differentiation. There were two types: endometrioid type, expressing NSEγ, and blastoma type, expressing neuropeptides. In contrast, similar morule-like features were epithelial nodules. Although the number of cases was small, the presence of morules showed no clear prognostic correlations.
Epidemiology of non-Hodgkin lymphomas in Tyrol/Austria from 1991 to 2000
Authors: Mitterlechner T , Fiegl M , Mühlböck H , Oberaigner W , Dirnhofer S , Tzankov A
Published: January 2006

Aims:To analyse the entity specific incidence and disease specific survival (DSS) of non-Hodgkin lymphomas (NHLs) in Tyrol/Austria, 1991–2000.

Methods:Data from 1307 NHLs (excluding primary cutaneous lymphomas and monoclonal gammopathies of undetermined significance) were obtained. Current status was available for all patients. Except for 29 cases of small lymphocytic (CLL/SLL), lymphoblastic leukaemia (ALL), and myeloma (MM), which were diagnosed cytologically, diagnoses were reclassified on paraffin wax embedded archival material according to new World Health Organisation criteria. Sex specific age adjusted standardised incidence rates were computed using Segi’s population weighting. Annual incidence changes were calculated by weighted least square regression analysis. Survival was estimated by the Kaplan–Meier method and compared by log rank test.

Results:NHL more frequently affected men (male/female ratio, 1.52). Mean age of occurrence was 61 and 66 years for men and women, respectively. The incidence rate of 14.3 remained constant. There was a significant increase in diffuse large B cell lymphoma (DLBCL) and decrease in CLL/SLL in men, and a decrease in MM in women. Overall DSS was 64% during the mean follow up (43 months). Age, T-NHL, λ light chain restriction in MM, and male sex in CLL/SLL were associated with poor prognosis. In B-NHL, DSS decreased in the following order: hairy cell leukaemia, marginal zone lymphoma, follicular lymphoma, Burkitt lymphoma, ALL, DLBCL, CLL, MM, and mantle cell lymphoma.

Conclusions:The incidence of NHL in Tyrol has changed in the past decade, with a significant increase in DLBCL, decrease in CLL/SLL in men, and decrease in MM in women.
Aberrant expression of VEGF-C is related to grade of cervical intraepithelial neoplasia (CIN) and high risk HPV, but does not predict virus clearance after treatment of CIN or prognosis of cervical cancer
Authors: Branca M , Giorgi C , Santini D , Di Bonito L , Ciotti M , Benedetto A , Paba P , Costa S , Bonifacio D , Di Bonito P , Accardi L , Favalli C , Syrjänen K
Published: January 2006

Aims:Increased angiogenesis leads to invasion in cervical cancer. Vascular endothelial growth factors (VEGFs) are involved in angiogenesis, but molecular links to the most important aetiological agent, human papillomavirus (HPV), need clarifying.

Material/Methods:Archival samples—150 squamous cell carcinomas (SCCs) and 152 cervical intraepithelial neoplasia (CIN) lesions—were examined immunohistochemically for anti-VEGF-C antibody and for HPV by polymerase chain reaction (PCR). Follow up data were available for all SCC cases, and 67 CIN lesions were monitored with serial PCR to assess HPV clearance/persistence after treatment.

Results:High risk (HR) HPV types were closely associated with CIN (odds ratio, 19.12; 95% confidence interval, 2.31 to 157.81) and SCC (27.25; 3.28 to 226.09). There was a linear increase of VEGF-C expression—weak in CIN1 and intense in CIN3 and SCC (20.49; 8.69 to 48.26). VEGF-C upregulation was a sensitive (93.5%; 95% CI, 90.1% to 96.9%) marker of HR-HPV type (4.70; 2.17 to 10.21), but lost its significance in multivariate regression—p16INK4aand survivin were equally strong independent predictors of HR-HPV. Aberrant expression of VEGF-C did not predict clearance/persistence of HR-HPV after treatment of CIN. In cervical cancer, VEGF-C had no prognostic value in univariate or multivariate survival analysis. After adjustment for HR-HPV, FIGO stage, age, and tumour grade, only FIGO stage and age remained independent prognostic predictors.

Conclusions:VEGF-C is an early marker of cervical carcinogenesis, with linearly increasing expression starting from low grade CIN. VEGF-C expression is closely related to HR-HPV in cervical lesions, probably because of its p53 independent upregulation by the E6 oncoprotein of HR-HPV.
Composite large cell neuroendocrine carcinoma and adenocarcinoma of the common bile duct
Authors: Sato K , Waseda R , Tatsuzawa Y , Fujinaga H , Wakabayashi T , Ueda Y , Katsuda S
Published: January 2006

Large cell neuroendocrine carcinoma (LCNEC) is a high grade type of neuroendocrine tumour with an aggressive clinical course. This report describes the first case of LCNEC combined with an adenocarcinoma component in the common bile duct. A 68 year old man presented with jaundice. Severe stenosis of the bile duct was revealed by endoscopic retrograde cholangiography, and adenocarcinoma cells were detected by brush cytology. Pancreaticoduodenectomy was performed, and the patient died of disease three months after surgery. A tumour measuring 2.0 cm in diameter was located in the intrapancreatic portion of the bile duct. Histologically, the tumour consisted of a LCNEC component and a well differentiated adenocarcinoma component. There were transitional areas between the two components. Immunohistochemically, LCNEC cells were reactive for neuroendocrine markers, but no specific hormonal expression was found. Chromogranin A positive cells were found in some areas of the adenocarcinoma component. These findings are consistent with the theory that both of the carcinoma components originated from a common pluripotent stem cell.
Importance of lymph vessels in gastric cancer: a prognostic indicator in general and a predictor for lymph node metastasis in early stage cancer
Authors: Nakamura Y , Yasuoka H , Tsujimoto M , Kurozumi K , Nakahara M , Nakao K , Kakudo K
Published: January 2006

Background:Metastasis to regional lymph nodes (LNs) through lymphatic vessels is common in cancer progression and is an important prognostic factor in many cancers. Recent evidence suggests that tumour lymphangiogenesis promotes lymphatic metastasis.

Aims:To study the role of lymph vessel density (LVD) in gastric cancer and investigate whether LVD is associated with LN metastasis/prognosis.

Methods:Lymphatics of 117 primary human gastric cancer cases were investigated by quantitative immunohistochemical staining for podoplanin. The relation between LVD and LN metastasis and other established clinicopathological parameters was analysed. The relation between LVD and prognosis was also studied.

Results:Mean LVD of “hot spots” was 11.6/case. LVD significantly correlated with LN and podoplanin positive lymphatic invasion. High LVD was associated with worse overall survival. In multivariate analysis, positive LVD was a significant independent predictor of overall survival, depth of invasion, and TNM stage. LVD significantly correlated with LN metastasis at surgery and podoplanin positive lymphatic invasion. In multivariate analysis, positive LVD was an independent significant predictor of LN metastasis.

Conclusions:Increased podoplanin expression is significantly associated with LN metastasis, and may play an important role in detecting LN metastasis in gastric cancer. Furthermore, LVD may be a significant prognostic factor in gastric cancer at any stage. In addition, LVD and lymph vessel invasion detected by podoplanin immunohistochemistry are associated with LN metastasis in T1 early gastric cancer. LVD assessment by podoplanin immunohistochemistry may become a useful predictor of LN metastasis in T1 early gastric cancer and may influence the decision making process for additional surgery.
PARABOLIC GROUPS ACTING ON ONE-DIMENSIONAL COMPACT SPACES
Authors: DAHMANI FRANÇOIS
Published: January 2006

Given a class of compact spaces, we ask which groups can be maximal parabolic subgroups of a relatively hyperbolic group whose boundary is in the class. We investigate the class of one-dimensional connected boundaries. We get that any non-torsion infinite finitely-generated group is a maximal parabolic subgroup of some relatively hyperbolic group with connected one-dimensional boundary without global cut point. For boundaries homeomorphic to a Sierpinski carpet or a 2-sphere, the only maximal parabolic subgroups allowed are virtual surface groups (hyperbolic, or virtually ℤ + ℤ).
ON GENERATORS OF THE TAME INVERTIBLE POLYNOMIAL MAPS GROUP
Authors: BODNARCHUK YURIY
Published: January 2006

The group TGAn of tame invertible polynomial maps is generated by the affine group AGLn and the triangular polynomial maps group Bn. In reality, for n > 2, Bn can be replaced by only one arbitrary nonlinear element, i.e., TGAn = 〈q, AGLn〉, q ∈ Bn\AGLn. Some classes of polynomial maps q, which have the same property are ascertained.
GEOMETRICAL APPROACH TO THE FREE SOLVABLE GROUPS
Authors: VERSHIK A. M. , DOBRYNIN S. V.
Published: January 2006

We give a topological interpretation of the free metabelian group, following the plan described in [11, 12]. Namely, we represent the free metabelian group with d-generators as an extension of the group of the first homology of the d-dimensional lattice (as Cayley graph of the group ℤd), with a canonical 2-cocycle. This construction opens a possibility to study metabelian groups from new points of view; in particular to give useful normal forms of the elements of the group, leading to applications to the random walks, and so on. We also describe the satellite groups which correspond to all 2-cocycles of cohomology group associated with the free solvable groups. The homology of the Cayley graph can be used for studying the wide class of groups which include the class of all solvable groups.
KAZHDAN CONSTANTS FOR SLn(ℤ)
Authors: KASSABOV MARTIN
Published: January 2006

In this article we improve the known Kazhdan constant for SL n(ℤ) with respect to the generating set of the elementary matrices. We prove that the Kazhdan constant is bounded from below by [Formula: see text], which gives the exact asymptotic behavior of the Kazhdan constant, as n goes to infinity, since [Formula: see text] is an upper bound.

We can use this bound to improve the bounds for the spectral gap of the Cayley graph of SL n(𝔽p) and for the working time of the product replacement algorithm for abelian groups.
Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men
Authors: Münzer Thomas , Rosen Clifford J. , Harman S.Mitchell , Pabst Katherine M. , Clair Carol St. , Sorkin John D. , Blackman Marc R.
Published: January 2006

Circulating GH, IGF-I, IGFBP-3, and sex steroid concentrations decrease with age. GH or sex steroid treatment increases IGFBP-3, but little is known regarding the effects of these hormones on other IGFBPs. We assessed the effects of 26 wk of administration of GH, sex steroids, or GH + sex steroids on AM levels of IGF-I, IGFBPs 1–5, insulin, glucose, and osteocalcin and 2-h urinary excretion of deoxypyridinolline (DPD) cross-links in 53 women and 71 men aged 65–88 yr. Before treatment, in women and men, IGF-I was directly related to IGFBP-3 ( P < 0.001 and P < 0.0001) and IGFBP-1 to IGFBP-2 ( P = 0.0001). In women, IGFBP-1 was inversely related to insulin ( P < 0.0005) and glucose ( P < 0.005) and IGFBP-4 to osteocalcin ( P < 0.01). IGFBP-4 and IGFBP-5 were not significantly related to DPD cross-links. GH and/or sex steroid increased IGF-I levels in both sexes, with higher concentrations in men ( P < 0.001). In women, the IGF-I increment after GH was attenuated by hormone replacement therapy (HRT) coadministration ( P < 0.05). Hormone administration also increased IGFBP-3. IGFBP-1 was unaffected by GH + sex steroids, whereas GH decreased IGFBP-2 by 15% in men ( P < 0.05). Hormone administration did not change IGFBP-4, whereas in men IGFBP-5 increased by 20% after GH ( P < 0.05) and 56% after GH + testosterone ( P = 0.0003). These data demonstrate sexually dimorphic IGFBP responses to GH. Additonally, HRT attenuated or prevented GH-mediated increases in IGF-I and IGFBP-3. Whether GH and/or sex steroid administration alters local tissue production of IGFBPs and whether the latter influence autocrine or paracrine actions of IGF-I remain to be determined.
Phenol injury-induced hypertension stimulates proximal tubule Na+/H+ exchanger activity
Authors: Leong Patrick K. K. , Yang Li E. , Landon Carol S. , McDonough Alicia A. , Yip Kay-Pong
Published: January 2006

Injection of 50 μl 10% phenol into rat renal cortex activates renal sympathetic nerve activity which provokes acute hypertension that persists for weeks. We have previously shown with membrane fractionation that phenol injury caused a redistribution of the main proximal tubule (PT) apical transporter NHE3 (Na+/H+ exchanger isoform 3) to low density membranes enriched in apical microvilli. The aim of this study was to determine whether phenol injury increases PT apical Na+/H+ exchanger (NHE) activity. NHE activity was measured in vivo as the initial rate of change in intracellular pH (dpHi/d t) during luminal Na+ removal in PT preloaded with the pH-sensitive fluorescence dye BCECF. Injection of 50 μl 10% phenol increased blood pressure from 113 ± 5.2 to 130 ± 4.6 mmHg without changing glomerular filtration rate or urine output. NHE activity increased 2.6-fold by 70 min after phenol injury. The increase of NHE activity was accompanied with an increase of tubular reabsorption. Total NHE activity/NHE3 protein in cortical brush-border membrane (BBM) vesicles, measured by acridine orange quench and immunoblot, respectively, was unchanged by phenol injury. In conclusion, acute phenol injury provokes coincident increases in PT apical NHE activity, redistribution of NHE3 into low density apical membranes, and hypertension. The increase in NHE activity may contribute to the lack of pressure-diuresis and the maintenance of chronic hypertension in this model.
QTL analysis of body composition and metabolic traits in an intercross between chicken lines divergently selected for growth
Authors: Park Hee-Bok , Jacobsson Lina , Wahlberg Per , Siegel Paul B. , Andersson Leif
Published: January 2006

The high- and low-growth lines of chickens have been developed from a single founder population by divergent selection for body weight at 56 days of age for more than 40 generations. The two lines show a ninefold difference in body weight at selection age and several interesting correlated selection responses such as altered body composition and metabolic differences. We have generated a reciprocal intercross comprising >800 F2birds. In a previous study, we reported the detection of 13 quantitative trait loci (QTLs) affecting growth. Here we report QTLs for body composition (fat deposition, muscle development), weight of internal organs, and metabolic traits (plasma concentrations of glucose, insulin, cholesterol, glucagon, triglycerides, and IGF-I). Most of the QTLs with convincing statistical support mapped in the vicinity of growth QTLs. One of the most interesting observations was that the type of reciprocal cross had highly significant effects on body weight at hatch and on plasma concentrations of glucose, cholesterol, insulin, and IGF-I, but it had no significant effect on body weight at 56 days of age. The reciprocal cross explained between 15 and 35% of the phenotypic variance for weight at hatch and for plasma concentrations of glucose and insulin. The observed pattern indicated that these effects were caused by maternal effects or by genetic differences in mitochondrial DNA.