bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xanthine oxidase inhibitor allopurinol attenuates the development of diabetic cardiomyopathy
Authors: Rajesh Mohanraj , Mukhopadhyay Partha , Bátkai Sándor , Mukhopadhyay Bani , Patel Vivek , Haskó György , Szabó Csaba , Mabley Jon G. , Liaudet Lucas , Pacher Pál 
Published: July 2009

AbstractIn this study, we investigated the effect of the xanthine oxidase (XO) inhibitor, allopurinol (ALP), on cardiac dysfunction, oxidative‐nitrosative stress, apoptosis, poly(ADP‐ribose) polymerase (PARP) activity and fibrosis associated with diabetic cardiomyopathy in mice. Diabetes was induced in C57/BL6 mice by injection of streptozotocin. Control and diabetic animals were treated with ALP or placebo. Left ventricular systolic and diastolic functions were measured by pressure–volume system 10 weeks after established diabetes. Myocardial XO, p22phox, p40phox, p47phox, gp91phox, iNOS, eNOS mRNA and/or protein levels, ROS and nitrotyrosine (NT) formation, caspase3/7 and PARP activity, chromatin fragmentation and various markers of fibrosis (collagen‐1, TGF‐β, CTGF, fibronectin) were measured using molecular biology and biochemistry methods or immunohistochemistry. Diabetes was characterized by increased myocardial, liver and serum XO activity (but not expression), increased myocardial ROS generation, p22phox, p40phox, p47phox, p91phox mRNA expression, iNOS (but not eNOS) expression, NT generation, caspase 3/7 and PARP activity/expression, chromatin fragmentation and fibrosis (enhanced accumulation of collagen, TGF‐β, CTGF and fibronectin), and declined systolic and diastolic myocardial performance. ALP attenuated the diabetes‐induced increased myocardial, liver and serum XO activity, myocardial ROS, NT generation, iNOS expression, apoptosis, PARP activity and fibrosis, which were accompanied by improved systolic (measured by the evaluation of both load‐dependent and independent indices of myocardial contractility) and diastolic performance of the hearts of treated diabetic animals. Thus, XO inhibition with ALP improves type 1 diabetes‐induced cardiac dysfunction by decreasing oxidative/nitrosative stress and fibrosis, which may have important clinical implications for the treatment and prevention of diabetic cardiomyopathy and vascular dysfunction.
Suppression of cellular immunity by cord blood‐derived unrestricted somatic stem cells is cytokine‐dependent
Authors: Winter Meike , Wang Xiao‐Nong , Däubener Walter , Eyking Annette , Rae Michelle , Dickinson Anne M. , Wernet Peter , Kögler Gesine , Sorg Rüdiger V. 
Published: July 2009

AbstractUnrestricted somatic stem cells (USSC) have the potential to differentiate into tissues derived from all three germinal layers and therefore hold promise for use in regenerative therapies. Furthermore, they have haematopoietic stromal activity, a characteristic that may be exploited to enhance haematopoietic engraftment. Both applications may require USSC to be used in an allogeneic, HLA‐mismatched setting. We have therefore studied their in vitro interaction with cellular immunity. USSC showed no allostimulatory activity and caused only minimal inhibition of allogeneic T‐cell responses. However, following pre‐stimulation with IFNγ and TNFα, they inhibited T‐cell proliferation in an indoleamine 2, 3‐dioxygenase‐dependent manner and suppressed graft‐versus‐host type reactions. In addition, USSC inhibited DC maturation and function. This inhibition was overridden by stronger DC maturation signals provided by IL‐1β, IL‐6, PGE2 and TNFα compared to TNFα alone. Pre‐stimulation of USSC with IFNγ and TNFα had a similar effect: Inhibition of DC maturation was no longer observed. Thus, USSC are conditionally immunosuppressive, and IFNγ and TNFα constitute a switch, which regulates their immunological properties. They either suppress T‐cell responses in the presence of both cytokines or in their absence block DC differentiation and function. These activities may contribute to fine‐tuning the immune system especially at sites of tissue damage in order to ensure appropriate differentiation of USSC and subsequent tissue repair. Therapeutically, they may help to protect USSC and possibly their progeny from immune rejection.
Interstitial cells from rat middle cerebral artery belong to smooth muscle cell type
Authors: Harhun Maksym I. , Szewczyk Kinga , Laux Holger , Prestwich Sally A. , Gordienko Dmitri V. , Moss Ray F. , Bolton Thomas B. 
Published: July 2009

AbstractIt is now established that non‐contractile cells with thin filopodia, also called vascular interstitial cells (VICs), are constitutively present in the media of many, if not all, blood vessels. The aim of this study was to determine the type of cell lineage to which arterial VICs belong using immunocytochemical, and real‐time and reverse transcription PCR (RT‐PCR). Using RT‐PCR, we compared gene expression profiles of single VICs and smooth muscle cells (SMCs) freshly dispersed from rat middle cerebral artery. Both VICs and SMCs expressed the SMC marker, smooth muscle myosin heavy chain (SM‐MHC), but did not express fibroblast, pericyte, neuronal, mast cell, endothelial or stem cell markers. Freshly isolated VICs also did not express c‐kit, which is the marker for interstitial cells of Cajal in the gastrointestinal tract. Immunocytochemical labelling of contractile proteins showed that VICs and SMCs expressed SM‐MHC similarly to the same degree, but VICs in contrast to SMCs had decreased expression of α‐SM‐actin and very low or no expression of calponin. Real‐time RT‐PCR was consistent with immunocytochemical experiments and showed that VICs had four times lower gene expression of calponin comparing to SMCs, which may explain VICs’ inability to contract. VICs had greater expression than SMCs of structural proteins such as non‐muscular β‐actin and desmin. The results obtained suggest that VICs represent a subtype of SMCs and may originate from the same precursor as SMCs, but later develop filopodia and a non‐contractile cell phenotype.
Invadopodia biogenesis is regulated by caveolin‐mediated modulation of membrane cholesterol levels
Authors: Caldieri Giusi , Giacchetti Giada , Beznoussenko Galina , Attanasio Francesca , Ayala Inmaculada , Buccione Roberto 
Published: July 2009

AbstractInvadopodia are proteolytically active protrusions formed by invasive tumoural cells when grown on an extracellular matrix (ECM) substratum. Clearly, invadopodia are specialized membrane domains acting as sites of signal transduction and polarized delivery of components required for focalized ECM degradation. For these reasons, invadopodia are a model to study focal ECM degradation by tumour cells. We investigated the features of invadopodia membrane domains and how altering their composition would affect invadopodia biogenesis and function. This was achieved through multiple approaches including manipulation of the levels of cholesterol and other lipids at the plasma membrane, alteration of cholesterol trafficking by acting on caveolin 1 expression and phosphorylation. We show that cholesterol depletion impairs invadopodia formation and persistence, and that invadopodia themselves are cholesterol‐rich membranes. Furthermore, the inhibition of invadopodia formation and ECM degradation after caveolin 1 knock‐down was efficiently reverted by simple provision of cholesterol. In addition, the inhibitory effect of caveolin 3DGV expression, a mutant known to block cholesterol transport to the plasma membrane, was similarly reverted by provision of cholesterol. We suggest that invadopodia biogenesis, function and structural integrity rely on appropriate levels of plasma membrane cholesterol, and that invadopodia display the properties of cholesterol‐rich membranes. Also, caveolin 1 exerts its function in invadopodia formation by regulating cholesterol balance at the plasma membrane. These findings support the connection between cholesterol, cancer and caveolin 1, provide further understanding of the role of cholesterol in cancer progression and suggest a mechanistic framework for the proposed anti‐cancer activity of statins, tightly related to their blood cholesterol‐lowering properties.
Expression of activated signal transducer and activator of transcription 3 predicts poor clinical outcome in gastric adenocarcinoma
Authors: LEE JEEYUN , KANG WON KI , PARK JOON OH , PARK SE HOON , PARK YOUNG SUK , LIM HO YEONG , KIM JUNGA , KONG JEEHYUN , CHOI MIN GEW , SOHN TAE SUNG , NOH JAE HYUNG , BAE JAE MOON , KIM SUNG , LIM DO HOON , KIM KYOUNG‐MEE , PARK CHEOL KEUN 
Published: July 2009

Lee J, Kang WK, Park JO, Park SH, Park YS, Lim HY, Kim J, Kong J, Choi MG, Sohn TS, Noh JH, Bae JM, Kim S, Lim DH, Kim K‐M, Park CK. Expression of activated signal transducer and activator of transcription 3 predicts poor clinical outcome in gastric adenocarcinoma. APMIS 2009; 117: 598–606.There are no known reliable biomarkers which can predict poor clinical outcome following curative resection of gastric adenocarcinoma. Given the importance of signal transducer and activator of transcription 3 (STAT3) activation in carcinogenesis, we attempted to determine whether STAT3 activation is prognostic of survival in curatively resected gastric cancer patients. We analyzed 311 surgically resected gastric cancer specimens for STAT3 activation and its downstream molecules such as matrix metalloproteinase (MMP)‐9, MMP‐10, cyclin D1, survivin, vascular endothelial growth factor (VEGF)‐C, and VEGFR‐3 using immunohistochemical studies and assessed their correlation with clinical outcome. Using immunohistochemistry, 303 specimens were interpretable for pSTAT3tyr705 expression. The pSTAT3 was detected in 79 (26.1%) of 303 gastric cancers. Of the downstream molecules tested, STAT3 activation was significantly associated with MMP‐9 and MMP‐10 expressions. On univariate analyses, 5‐year disease‐free survival (DFS) and overall survival (OS) for the tumors with STAT3 activation were considerably poorer than for those without STAT3 activation with statistical significance (5‐year DFS 58.2% vs 68.3%; pSTAT3(−) vs pSTAT3(+); p = 0.0223; 5‐year OS 59.5% vs 70.5%; pSTAT3(−) vs pSTAT3(+); p = 0.0128). On multivariate analyses, STAT3 activation was independently associated with inferior DFS (p = 0.049, hazard ratio [HR] = 1.445, 95% CI, 1.025, 2.120) along with AJCC stage IIIA or IIIB (p = 0.004, HR = 1.708, 95% CI, 1.178, 2.475). The STAT3 activation was also strongly correlated with inferior OS (p = 0.042, HR = 1.506, 95% CI, 1.025, 2.213). Based on our data, pSTAT3tyr705 may be a novel prognostic marker for poorer clinical outcome following curative resection and adjuvant therapy in gastric cancer. The clinical impact of a STAT3‐targeted agent should be investigated in gastric cancer patients.
Analysis of telomere length in mantle cell lymphoma
Authors: Cottliar Alejandra S. H. , Panero Julieta , Pedrazzini Estela , Noriega Maria Fernanda , Narbaitz Marina , Rodríguez Andrea , Slavutsky Irma 
Published: July 2009

AbstractMantle cell lymphoma (MCL) is a well defined lymphoid neoplasm genetically characterized by the t(11;14)(q13;q32). Telomeres play an essential role in preserving chromosomal integrity and genomic stability; their shortening can lead to telomere dysfunction and chromosomal instability, a critical factor in cancer development. In this study, telomere length (TL) measured by terminal restriction fragments (TRF) assay in DNA samples of tumor cells from 20 patients with MCL was evaluated. Results were correlated with clinical, morphologic and cytogenetic characteristics. In all cases, the presence of the CCND1/IGH@ rearrangement was confirmed by fluorescence in situ hybridization and/or PCR analysis. TL in total MCL patients revealed a mean TRF value (4.51 ± 0.79 kb) significantly shorter than those observed in controls (7.49 ± 1.94 kb) (P < 0.001); 30% of patients had TL shorter than 4.0 kb. TRF length was not associated with patients age (P = 0.07; r = 0.17) nor with sex (females: 4.33 ± 0.51 kb and males: 4.57 ± 0.85 kb; P = 0.63). No significant differences were found between patients studied at diagnosis (13) (4.44 ± 0.81 kb) respect to those analyzed at relapse (7) (4.63 ± 0.82 kb) (P = 0.53). In addition, we compared patients with (4.84 ± 1.09 kb) and without (4.40 ± 0.68 kb) complex karyotypes (P = 0.45) and cases with typical morphology (4.48 ± 0.79 kb) vs. blastoid variant (4.63 ± 1.04 kb) (P = 0.83), and no significant differences between them were found. Although the number of cases of our series is not large, our results showed that TL reduction in MCL is independent of the clinical characteristics, morphology and karyotype.
Heart rate variability in beta‐thalassemia patients
Authors: Rutjanaprom Wasarut , Kanlop Natnicha , Charoenkwan Pimlak , Sittiwangkul Rekwan , Srichairatanakool Somdet , Tantiworawit Adisak , Phrommintikul Arintaya , Chattipakorn Siriporn , Fucharoen Suthat , Chattipakorn Nipon 
Published: July 2009

AbstractBackground:  Cardiac failure remains the major cause of death in beta‐thalassemia major (TM). Reduced heart rate variability (HRV) is associated with a higher risk of arrhythmias after myocardial infarction and heart failure. We evaluated HRV in TM patients and its relationship with hemodynamics and echocardiographic parameters during a 6‐month follow‐up.Methods:  Thirty‐four TM patients (19 ± 10 yr) and 20 healthy subjects (17 ± 6 yr) were evaluated. Hematologic, biochemical, echocardiographic and HRV parameters were determined at entry and at 6‐month follow‐up. Time and frequency domain HRV parameters were analyzed from 24‐h recorded electrocardiograms. All TM patients received blood transfusion and chelation therapy.Results:  Both time and frequency domain HRV parameters were markedly reduced in TM patients, compared to the control. The significantly improved HRV was seen in correlation with higher hemoglobin (Hb) level when compared within TM group at different time point. No correlation was seen between HRV and serum ferritin, reactive oxygen species (ROS) and non‐transferrin bound iron (NTBI).Conclusion:  HRV is depressed in TM patients. HRV was significantly correlated with Hb level, suggesting that anemia greatly influences the cardiac autonomic balance.
Interphase FISH on TEL/AML1 positive acute lymphoblastic leukemia relapses – analysis of clinical relevance of additional TEL and AML1 copy number changes
Authors: Peter Anita , Heiden Thomas , Taube Tillmann , Körner Gabriele , Seeger Karl 
Published: July 2009

AbstractObjectives:  TEL/AML1 (ETV6/RUNX1) fusion resulting from the translocation t(12;21)(p13;q22) constitutes the most common chimeric fusion gene in initial childhood B‐cell precursor (BCP) acute lymphoblastic leukemia (ALL) (19–27%) and has been associated with good prognosis. Three secondary aberrations in TEL/AML1 positive ALL have been suspected to negatively influence outcome: deletion of the second TEL allele (T), gain of the second AML1 allele (A) and duplication of the derivative chromosome 21 (der(21), TA). Many studies have explored such aberrations in initial disease, while only few reports have investigated them in relapses.Methods:  In this study, bone marrow samples from 38 children with relapsed TEL/AML1 RT‐PCR positive and negative BCP‐ALL were analyzed for these mutations by interphase fluorescence in situ hybridization and results were compared with published data.Results:  In children with TEL/AML1 positive ALL relapse, additional (a) TEL loss, (b) combined AML1 and der(21) gain, (c) combined TEL loss and AML1 gain as well as (d) the occurrence of a subpopulation with the signal pattern 1T/3A/1TA appear to be related to higher peripheral blast counts (PBCs) at relapse diagnosis (a and d) or a tendency towards the occurrence of a subsequent relapse (b and c) (P‐values <0.05).Conclusions:  Our data together with published results on TEL/AML1 positive ALL suggest that frequencies of additional TEL and AML1 mutations are, with the exception of loss of untranslocated TEL, higher in first relapses than in initial disease. They also show that it is important to consider combined mutations in the analysis of this leukemia entity.
Sonographic biometrical normograms and estimation of fetal weight in the baboon (Papio anubis)
Authors: Van Calsteren K. , De Catte L. , Devlieger R. , Chai D.C. , Amant F. 
Published: July 2009

AbstractBackground  In order to consider the non‐human primate as an adequate model for studying prenatal diagnosis and therapy, comparative data on fetal growth should be available.Methods  Sixty ultrasound scans were performed in 22 baboons between 14 and 167 days of gestation. Measurements included greatest length, head circumference, biparietal diameter (BPD), transcerebellar diameter, abdominal circumference (AC), femur length (FL), and amniotic fluid index. For all parameters growth curves were established and compared with human curves. In 18 animals, birth weight and placental weight were determined. Different equations described in the literature for estimating the human fetal weight were tested in the baboon.Results  The fetal and placental growth pattern in the baboon was comparable with humans. The best predictor of fetal weight was the formula presented by Combs: 0.23966 × AC2 × FL + 1.623 × BPD3.Conclusions  A high similarity between baboon and human growth charts is shown. The best equation for estimating the baboon fetal weight is proposed.
Release of Juniperus thurifera woodlands from herbivore‐mediated arrested succession in Spain
Authors: DeSoto Lucía , Olano José Miguel , Rozas Vicente , De la Cruz Marcelino 
Published: July 2009

AbstractQuestion: Do abiotic constraints maintain monospecific woodlands of Juniperus thurifera? What is the role of biotic (livestock) versus abiotic (climate) drivers in the recruitment and growth of the different tree species?Location: Cabrejas range, Soria, north‐central Spain, 1200 m altitude.Methods: Stand history was reconstructed using dendro‐ecology and spatial pattern analysis, combined with historical data of livestock abundances and climatic records.Results: J. thurifera establishment occurred in two distinct pulses, with a tree component establishing in the late 1800s to early 1900s. Quercus ilex and Pinus sylvestris establishment was evident only from the late 1970s onward. Recruitment events were related to reductions in livestock browsing. J. thurifera spatial structure was clumped and Q. ilex showed a short‐scale aggregation to J. thurifera trees and saplings. Radial growth trends of J. thurifera saplings, Q. ilex and P. sylvestris were negatively related to livestock density. Summer drought limited the radial growth of all the study species, and P. sylvestris and Q. ilex grew faster than J. thurifera even after considering an age effect.Conclusions: The differences in radial growth patterns and recruitment pulses between species indicate that livestock browsing and not abiotic factors is the main factor controlling plant succession and structural development. In this process, J. thurifera acts as a nurse plant, facilitating the establishment of other tree species. Under the current low pressure from herbivores, formerly pure J. thurifera woodlands will change towards dense stands of mixed species composition.
Habitat degradation, topography and rainfall variability interact to determine seed distribution and recruitment in a sand dune grassland
Authors: Li Feng‐Rui , Zhao Li‐Ya , Zhang Hua , Liu Ji‐Liang , Lu Hai‐Yan , Kang Ling‐Fen 
Published: July 2009

AbstractQuestion: Understanding the mechanisms underlying how habitat degradation, topography and rainfall variability interactively affect seed distribution and seedling recruitment is crucial for explaining plant community patterns and dynamics. Interactions between these major factors were studied together in a semiarid sand dune grassland.Location: Eastern Inner Mongolia, China.Methods: The study system used four sites of fixed, semifixed, semishifting and shifting sand dune grasslands, representing a gradient of habitat degradation. We investigated the density of germinable seeds deposited in the top 5 cm of soil and in situ seedling emergence (number of seedlings emerging early in the growing season) and establishment (number of plants recruited at the end of the growing season) at three topographic positions (dune top, windward and leeward sides) within each site over 2 years that differed in rainfall. Habitat characteristics (i.e. vegetation cover, plant species composition and diversity, soil moisture and nutrient availability and soil erodibility) of the four sites were also measured.Results: Habitat degradation (i.e. decreased vegetation cover and enhanced wind erosion rate) significantly reduced the size of the germinable soil seed bank. On average, germinable seed number from the high‐vegetation cover fixed dune was 36‐fold larger than the low‐vegetation cover shifting dune, and eight‐ and two‐fold larger, respectively, than the semishifting and semifixed dunes with intermediate vegetation cover. We observed within‐habitat variability in seed distribution, but among‐topographic position variation differed among habitats. Seedling recruitment showed large between‐year, and among‐ and within‐habitat variability, but these variations varied significantly depending on the response variables evaluated (i.e. initial seedling density, final plant density, emergence rate and recruitment rate). Path analysis revealed complex density‐dependent positive and negative, direct and indirect effects of germinable seed density and initial seedling density on recruitment, but the relative importance of these density‐dependent effects varied depending on habitat type and rainfall availability.Conclusion: Our results suggest that habitat degradation, microtopography and rainfall availability interact in shaping sand dune seed bank and plant community recruitment patterns and dynamics. Their effects were mainly mediated through changes in both the biotic and abiotic environment during the process of habitat deterioration.
Progression of Lipid Peroxidation Measured as Thiobarbituric Acid Reactive Substances, Damage to DNA and Histopathological Changes in the Liver of Rats Subjected to a Methionine–Choline‐Deficient Diet
Authors: Jordao Alceu Afonso , Zanutto Marcia Elena , Domenici Fernanda Aparecida , Portari Guilherme Vannucchi , Cecchi Andréa Oliveira , Zucoloto Sergio , Vannucchi Helio 
Published: July 2009

Abstract:  Methionine–choline‐deficient diet represents a model for the study of the pathogenesis of steatohepatitis. Male rats were divided into three groups, the first group receiving a control diet and the other two groups receiving a methionine–choline‐deficient diet for 1 month (MCD1) and for 2 months (MCD2), respectively. The livers of the animals were collected for the determination of vitamin E, thiobarbituric acid reactive substances (TBARS), GSH concentration, DNA damages, and for histopathological evaluation. The hepatic TBARS and GSH content was higher (P < 0.05) in the groups receiving the experimental diet (MCD1 and MCD2) compared to control diet, and hepatic vitamin E concentration differed (P < 0.05) between the MCD1 and MCD2 groups, with the MCD2 group presenting a lower concentration. Damage to hepatocyte DNA was greater (P < 0.05) in the MCD2 group (262.80 DNA injuries/100 hepatocytes) compared to MCD1 (136.4 DNA injuries/100 hepatocytes) and control diet (115.83 DNA injuries/100 hepatocytes). Liver histopathological evaluation showed that steatosis, present in experimental groups was micro‐ and macro‐vesicular and concentrated around the centrolobular vein, zone 3, with preservation of the portal space. The inflammatory infiltrate was predominantly periductal and the steatosis and inflammatory infiltrate was similar in the MCD1 and MCD2 groups, although the presence of Mallory bodies was greater in the MCD2 group. The study describes the contribution of a methionine–choline‐deficient diet to the progression of steatosis, lipid peroxidation and hepatic DNA damage in rats, serving as a point of reflection about the role of these nutrients in the western diet and the elevated non‐alcoholic steatohepatitis rates in humans.