bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender differences in circulating bubble production after SCUBA diving
Authors: Boussuges Alain , Retali Gerald , Bodéré‐Melin Mathilde , Gardette Bernard , Carturan Daniel
Published: July 2009

Objective:  Differences in circulating bubble production have been described after exposures in altitude chambers between men and women. The present study was designed to examine gender differences in circulating bubble production after a dive.

Methods:  Fifty‐two men and 52 women performed the same dive profile (25 min to 35 m). Circulating bubbles were detected by continuous wave Doppler. Tests were conducted at sea in a boat, at 10‐min intervals for 1 h after surfacing. Signals were graded according to the Spencer scale. The categorical data were then converted to a single number reflecting total bubble activity using the KISS index.

Results:  Considering each measurement period, bubble grade was higher in men than women 30, 40 and 50 min postdive. On the contrary, bubble grade was comparable between men and women 10, 20 and 60 min after the dive. KISS index was significantly higher in men than women (6·77 [0·65–32·3] versus 0·91 [0–22·9], P<0·02). KISS index was significantly correlated with age, weight and body fat mass in the whole population and in the men and women separately. Postmenopausal women had a higher KISS index (42 [15–47]) when compared with premenopausal women and men older than 50 years. No difference in bubble production was found according to the use of oral contraceptive pills or the phase of the menstrual cycle.

Conclusion:  Overall, we observed fewer circulating bubbles in women than in men after an open sea SCUBA dive. This difference disappeared in the postmenopausal women.
EVALUATING CONTEMPORANEITY AND POST‐MORTEM AGE OF MALACOLOGICAL REMAINS USING SCLEROCHRONOLOGY AND DENDROCHRONOLOGY*
Authors: HELAMA S. , NIELSEN J. K. , VALOVIRTA I.
Published: July 2009

Sclerochronology and dendrochronology are based on series of incremental skeletal and cambial growths that have been correctly aligned in time via cross‐dating (i.e., incremental dating through synchronization of the growth variability on a visual and statistical basis). Here we report a study of the shell increments of two anthropogenic death assemblages of freshwater pearl mussel (Margaritifera margaritifera) originating from Finnish Lapland. First, we cross‐dated a new sclerochronology from an assemblage of river pearl mussel shells with unknown post‐mortem age. Second, this chronology was cross‐dated with the previously published sclerochronology of the same species and geographical source. Third, the composite of the two sclerochronologies was compared to dendrochronologies from Lapland. Temporal association of the two types of chronologies was markedly high, as confirmed byt‐values of 7.1 and 8.9, which are well above the acceptable limit of 3.5. Our study demonstrates the potential of sclerochronological and dendrochronological materials and techniques in assessing the contemporaneity (i.e., temporal overlap) and post‐mortem age of archaeomalacological deposits. In the palaeontological context, these results also show the wider possibility of dating shells with a large number of annual increments from natural deposits.
A PROVENANCE STUDY OF THE GILGAMESH FRAGMENT FROM MEGIDDO
Authors: GOREN Y. , MOMMSEN H. , FINKELSTEIN I. , NA'AMAN N.
Published: July 2009

A Late Bronze Age fragment of a clay cuneiform tablet with the Gilgamesh Epic was found in the 1950s on the surface at Megiddo. The presence of scribes in Megiddo is evident from the el‐Amarna letters. This is the only first‐class literary Mesopotamian text ever to be found in Canaan. The aim of the present study was to examine the origin of this tablet, by mineralogical and elemental methods. The petrographic and NAA results indicate that the tablet was not Mesopotamian, but was written in southern Israel. The implications of this result in view of the small corpus of scholarly cuneiform texts discovered in Egypt and the southern Levant in the second millennium bce are discussed.
Cholangiocytes as immune modulators in rotavirus‐induced murine biliary atresia
Authors: Barnes Barrett H. , Tucker Rebecca M. , Wehrmann Fabian , Mack Doug G. , Ueno Yoshiyuki , Mack Cara L.
Published: July 2009

Background/Aims: Biliary atresia (BA) is a progressive disease characterized by bile duct inflammation and fibrosis. The aetiology is unknown and may be due to a virus‐induced, autoimmune‐mediated injury of cholangiocytes. Cholangiocytes are not only targets of injury but may also modulate hepatic inflammation. The aim of this study was to determine the immune profile of murine cholangiocytes and the ability to function as antigen‐presenting cells (APCs) in culture with Rhesus rotavirus (RRV), poly I:C (viral mimic) or interferon‐γ/tumour necrosis factor‐α.

Methods/Results: Both the cholangiocyte cell line (long‐term culture) and fresh, ex vivo cholangiocytes expressed APC surface markers major histocompatibility complex (MHC)‐class I and II and CD40, while only the cultured cell line expressed costimulatory molecules B7‐1 and B7‐2. Despite APC expression, cultured cholangiocytes were unable to function as competent APCs in T‐cell proliferation assays. Furthermore, both cultured and ex vivo cholangiocytes expressed RNA transcripts for many pro‐inflammatory cytokines and chemokines.

Conclusions: Although cholangiocytes contain APC molecules, they are incompetent at antigen presentation and cannot elicit effective T‐cell activation. Upregulation of MHC‐class I and II found in BA mice may serve to prime the cholangiocyte as a target for immune‐mediated injury. Cholangiocytes produced many pro‐inflammatory cytokines and chemokines in the setting of RRV infection and T‐helper type 1 cytokine milieu, suggesting a role of cholangiocytes as immune modulators promoting the ongoing inflammation that exists in RRV‐induced BA.
Predictors of nonresponse to lactulose for minimal hepatic encephalopathy in patients with cirrhosis
Authors: Sharma Praveen , Sharma Barjesh Chander , Sarin Shiv Kumar
Published: July 2009

Background/Aims: Minimal hepatic encephalopathy (MHE) impairs health‐related quality of life and predicts overt hepatic encephalopathy (HE) in cirrhotic patients. Lactulose is effective in the treatment of MHE. However, not all patients respond to lactulose. We evaluated predictors of nonresponse to lactulose.

Patients and methods: Consecutive 110 cirrhotic patients without HE were evaluated for MHE by psychometry, P300 auditory event‐related potential (P300ERP), venous ammonia and critical flicker frequency (CFF). MHE was diagnosed by abnormal psychometry and P300ERP (>2 SD). MHE patients were treated with lactulose for 1 month. Response was defined by normalization of the abnormal test parameters (both psychometric tests and P300ERP).

Results: Sixty patients (54.5%) were diagnosed as having MHE: 17/39 (44%) in Child's A, 21/42 (50%) Child's B and 22/29 (76%) in Child's C. There was a significant difference between Child's C's vs Child's A's and B's (P<0.05). Abnormal psychometric tests and abnormal P300ERP were seen in 74 (67%) and 74 (67%) patients respectively. Of 60 patients with MHE, after treatment, psychometry remained abnormal in 22 (36.6%) and P300ERP in 21 (35%) patients. CFF was<38 Hz in 34 (57%) and 11 (18%) patients, respectively, before and after treatment in MHE patients. There was a significant difference between the baseline serum sodium level (134.7±2.6 vs 131.1±2.2 mmol/L, P=0.001) and the venous ammonia level (76.6±20.7 vs 113.4±22.8 μmol/L, P=0.001) between responders vs nonresponders. Receiver operating characteristic analysis was performed to identify the cutoff for venous ammonia [cutoff 93.5 mmol/L, area under the curve (AUC) 0.892 (0.814–0.970)] and for the serum sodium level [cutoff 132.5 mmol/L, AUC 0.874 (0.779–0.998)]. Taking a cutoff of 93.5 mmol/L for ammonia patient had a sensitivity of 88.5% and a specificity of 79.4%, respectively, and a cutoff of 132.5 mmol/L for serum sodium patient had a sensitivity of 76.5% and a specificity of 88.5% for nonresponse to lactulose. On univariate analysis and multivariate analysis, serum sodium and venous ammonia were the only two parameters associated with nonresponse to lactulose.

Conclusion: The prevalence of MHE was 55% and MHE improved in 57% patients with lactulose. Baseline low serum sodium and high venous ammonia were highly predictive of nonresponse to lactulose therapy.
Interleukin‐10 promoter polymorphisms in hepatitis C patients with and without Schistosoma mansoni co‐infection
Authors: Abbas Omaima M. , Abdel‐Rahman Mohamed H. , Omar Nabil A. , Badran Hanaa M. , Amir Elamir M.
Published: July 2009

Background/Aim: Interleukin (IL‐10) plays a major role in chronic hepatitis C virus (HCV) disease pathogenesis, in particular in Schistosoma mansoni (S. mansoni) co‐infected patients. Given that interindividual variations in IL‐10 production are influenced by functional polymorphisms in the IL‐10 gene promoter, we determined the frequencies of common (−1082, −819 and −592) IL‐10 promoter polymorphisms in chronic HCV patients with and without S. mansoni co‐infection and healthy controls, and investigated their association with the degree of histological activity index (HAI) and response to interferon–ribavirin therapy.

Methods: Genomic DNA from 99 patients and 62 healthy controls, born in the same geographical hyperendemic area, was studied by the polymerase chain reaction, followed by restriction enzyme digestion. Sera were assessed for S. mansoni antibodies.

Results: The frequencies of IL‐10 polymorphisms at positions −1082, −819 and −592 from the transcription start site were comparable between HCV patients and controls, as well as between HCV mono‐infected and either S. mansoni co‐infected patients or controls. The grade of inflammation and the stage of fibrosis showed no association with IL‐10 polymorphisms. The frequencies of S. mansoni co‐infection and IL‐10 genotypes/haplotypes were insignificantly different between non‐responders and responders to combination therapy. No effect of other factors like age, gender, HAI group scores and serum alanine aminotransferase and aspartate aminotransferase levels was observed on response to therapy in our patients.

Conclusion: Our findings suggest that common IL‐10 (−1082, −819 and −592) genotypes/haplotypes do not influence the degree of HAI and response to combination therapy or susceptibility to HCV infection with and without S. mansoni co‐infection.
The stable isotope ketoisocaproic acid breath test as a measure of hepatic decarboxylation capacity: a quantitative analysis in normal subjects after oral and intravenous administration
Authors: Berthold Heiner K. , Giesen Thomas A. H. , Gouni‐Berthold Ioanna
Published: July 2009

Background and aims: There is no generally accepted kinetic evaluation method for the stable isotope [13C]ketoisocaproic acid (KIC) breath test. Differences found in the results between women and men are contradictory.

Methods: Oral and intravenous breath tests using 1 mg/kg stable isotope‐labelled KIC were performed in healthy male and female volunteers. A power exponential function was fitted to the mass spectrometric data of breath 13CO2 enrichment, allowing mathematical analysis of time‐to‐peak‐excretion, half‐excretion time, percent label recovery and parameters describing the shape of the curve. Body composition was determined using bioelectrical impedance analysis.

Results: After oral administration, total label recovery after 3 h was about 22% and was not different between men (n=7) and women (n=8). The time to maximal label excretion was 0.67 ± 0.12 h in men and 0.9 ± 0.32 h in women (P=0.028) and the excretion curve showed an initially slower rise in women compared with men. Adjusting for lean body mass or body water abrogated the sex differences. Total label recovery after intravenous administration was about 9%, suggesting that the substrate was rapidly catabolized in the muscle compartment after intravenous administration.

Conclusions: The modified power exponential function described allows standardized estimates of the KIC breath test results. When corrected for body composition, there are no differences in breath test results between men and women. The comparison between oral and intravenous results provides robust evidence that the KIC breath test measures predominantly hepatic and not muscle decarboxylation and is thus a highly specific liver function test.
Psychosocial Considerations for Children and Young Adolescents with Implantable Cardioverter Defibrillators: An Update
Authors: SEARS SAMUEL F. , AMANT JAY B. ST. , ZEIGLER VICKI
Published: July 2009

Background: The extension of the life‐saving benefits of the implantable cardioverter‐defibrillator (ICD) to prevent sudden cardiac arrest in children and young adults represents a key clinical development. The psychosocial adjustment in young ICD patients has not been as well‐studied as in adults and remains an area of needed research.

Methods: The current paper reviews the quantitative research regarding ICD patient psychosocial outcomes in the adult and pediatric literature, and highlights existing intervention research on adult ICD patients and its implications for young ICD patients.

Results: Literature review indicates that anxiety may be the most problematic psychosocial reaction for young ICD patients, similar to adult patients. Since young ICD patients appear to be more likely to experience shocks than adults; shock‐related anxiety is suspected to be particularly common. Interventions in adults have shown a reduction in anxiety but no pediatric intervention studies are currently available in the literature.

Conclusion: Additional research and clinical attention is warranted to further assist young ICD patients to achieve desirable quality of life outcomes.
Attitudes and Attributions Associated With Female and Male Partner Violence1
Authors: Robertson Kirsten , Murachver Tamar
Published: July 2009

In an interview study, we examined attitudes toward intimate partner violence (IPV). We examined whether attitudes toward IPV varied as a function of sample (student, general, and incarcerated), participant gender, and abuse history, or as a function of perpetrator gender. Additionally, participants' conflict‐resolution strategies were examined. Findings revealed that perpetrator gender and participant abuse history were the most influential factors in shaping attitudes. Males and females evaluated violence similarly. Overall, there was greater acceptance for abuse perpetrated by females than by males, and participants who had either perpetrated or received abuse were the most condoning of IPV. A lack of conflict skills was associated with IPV. For males, this lack of skills generalized to situations outside of the relationship.
In the Eye of the Beholder: Do Behavior and Character Affect Victim and Perpetrator Responsibility for Acquaintance Rape?1
Authors: Cohn Ellen S. , Dupuis Erin C. , Brown Tiffany M.
Published: July 2009

Acquaintance rape attributions of responsibility were investigated. In Study 1, participants viewed videotapes that varied the female victim's resistance (verbal, physical, verbal/physical) and the reaction of the perpetrator (anger, no reaction) or a control videotape. The victim was held less responsible and the perpetrator was held more responsible when the victim resisted. In Study 2, participants viewed videotapes that manipulated victim and perpetrator reputation. Victims were held more responsible when they had a bad reputation; perpetrators were held more responsible when the victim had a good reputation or the perpetrator had a bad reputation. Hostile sexism predicted victim responsibility in both studies; rape myth predicted victim and perpetrator responsibility in Study 2. Implications for the legal system are discussed.
The Role of Leader Morality in the Interaction Effect of Procedural Justice and Outcome Favorability
Authors: Lin Xiao‐Wan , Che Hong‐Sheng , Leung Kwok
Published: July 2009

The present research explored the role of leader morality in the interaction effect of procedural justice and outcome favorability, and attempted to connect justice and morality construct in a new direction. Two studies in different settings and using different designs (a scenario experiment and a survey) yielded convergent results. When leader morality was high, the interaction effect of procedural justice and outcome favorability was significant, and fair procedures mitigated the negative effect of low outcome favorability. When leader morality was low, however, the interaction between procedural justice and outcome favorability was absent.
Let Go or Retain? A Comparative Study of the Attitudes of Business Students and Managers About the Retirement of Older Workers
Authors: Henkens Kène , Van Solinge Hanna , Cozijnsen Rabina
Published: July 2009

This study's central research question is: “How do managers evaluate the desirability of early retirement of their employees, and under what circumstances and for what types of workers are they in favor of delay?” We sought to compare managers' and business students' decision making regarding older workers. We examined the extent to which student samples are appropriate to study organizational behavior. An identical factorial survey was carried out among 26 managers and 25 business school students. The results revealed that business students concentrate on performance‐related individual characteristics when making selection decisions, whereas managers also recognize contextual factors (need for downsizing, tight labor market) and older workers' attitudes toward retirement.
Implications of Virtual Management for Subordinate Performance Appraisals: A Pair of Simulation Studies
Authors: Golden Timothy D. , Barnes‐Farrell Janet L. , Mascharka Peter B.
Published: July 2009

This article shifts the focus of prior research examining virtual work to investigate how supervisors who work virtually use subordinate performance information. Drawing insights from several research streams, in Study 1, we propose that supervisors who work virtually bias performance ratings in the direction of information that is observed directly in the office, rather than that which is received when working virtually. In Study 2, we replicate and extend these results to show that this bias is independent of the level of performance information received. Results also indicate that, for high‐performing workers, performance information received virtually is evaluated more extremely than information observed directly. We did not find evidence for this extremity effect when low‐performing workers were evaluated.
Person Perception in the College Classroom: Accounting for Taste in Students' Evaluations of Teaching Effectiveness
Authors: Gross Jennifer , Lakey Brian , Edinger Kristin , Orehek Edward , Heffron Denise
Published: July 2009

An important applied aspect of person perception occurs when college students evaluate their professors' teaching. Student evaluations of teaching typically are conceptualized as reflecting the characteristics of professors. Yet, this view overlooks the possibility that teaching evaluations also reflect the personal tastes of students, manifested as systematic disagreement among students. Large effects of personal tastes are routinely observed in person perception research and, therefore, should be expected in students' evaluations of teaching. This article describes 3 studies in which students evaluated the same professors' teaching effectiveness. In each study, students' evaluations were strongly influenced by their personal tastes regarding teaching. Moreover, personal tastes in teaching were related in meaningful ways to students' positive affect and memory for lectures.
Solving the Dilemma: Family Communication About Organ Donation Among Chinese, Japanese, and Caucasian American College Students1
Authors: Wu Anise M. S. , Tang Catherine S.
Published: July 2009

This study surveyed 800 students in the United States, Hong Kong, and Japan to determine associations between the components of the theory of reasoned action and early communication about organ‐donation decisions within the family. Results showed that among the 3 ethnic groups, Japanese students reported the least favorable attitudes and subjective norms about organ donation and were also the least likely to discuss this topic with their families. Moreover, the moderating effect of ethnicity indicated that attitudes were a significant factor of family discussion among American and Japanese students but not among Chinese students. Subjective norms were more predictive of family discussion among Chinese students than among American and Japanese students.
Race Shapes Perceptions of Juvenile Offenders in Criminal Court1
Authors: Stevenson Margaret C. , Bottoms Bette L.
Published: July 2009

We investigated the effects of defendant race, victim race, and juror gender on non‐African American mock jurors' perceptions of crimes committed by juvenile offenders. We predicted that mock jurors, particularly men, would render more pro‐prosecution case judgments when the defendant was African American than White. We also predicted that defendants would be judged more harshly when the crime victim was portrayed as White rather than as African American. Although there were few main effects of defendant race or victim race on case judgments, defendant and victim race by juror gender interactions revealed that men (but not women) demonstrated the predicted bias against African American defendants and victims. Explanations and implications are discussed.
Predictive Factors of Ethnic Prejudice Toward Immigrants in a Representative Subsample of Spanish Young People1
Authors: González‐Castro José Luis , Ubillos Silvia , Ibáñez Jaime
Published: July 2009

This research aimed to study those factors that predict different types of ethnic prejudice in a representative subsample of Spanish young people. The instrument we used was Pettigrew & Meertens' (1995) blatant/subtle prejudice scale. Results show that although there is a similar underlying pattern in both types of ethnic prejudice, subtle prejudice is based more on cultural differences, whereas blatant prejudice also stresses the racial, economic, and labor effects of immigration. Moreover, blatant prejudice is also influenced by the formal level of education and political position. The results are interpreted within the Spanish context; and the implications for identity formation and maintenance, and practical programs directed toward ethnic prejudice awareness are discussed.
Psychological Reactance and Adolescents' Attitudes Toward Tobacco‐Control Measures
Authors: Wiium Nora , Aarø Leif E. , Hetland Jørn
Published: July 2009

The theory of psychological reactance predicts that, to the extent that smoking‐control measures are perceived as threatening the individual's freedom to choose among behavioral alternatives, they may be met with resistance. Data were collected from a national representative sample of 2,400 young people (ages 16–20) by telephone interviews. Dispositional reactance was shown to be associated with smoking. Principal components analyses revealed that a distinction should be made between attitudes toward weak and attitudes toward strong smoking‐control measures. Attitudes toward strong measures were particularly negative among regular smokers. Among regular smokers, dispositional reactance was found to be significantly associated with attitudes toward strong tobacco‐control measures. Processes of psychological reactance deserve attention when designing smoking control programs.
Influences of Upstream Social Factors on Downstream Perceptions of Social Support in Cardiac Rehabilitation1
Authors: Fraser Shawn N. , Rodgers Wendy M.
Published: July 2009

Within Berkman et al.'s (2000) framework, we examined sociodemographic correlates of social networks (SN) and social support (SS) in 155 heart patients (33 women, 122 men), who completed measures of sociodemographics, SN, and SS. Hierarchical regression analyses examined the relationship between sociodemographic factors and SN; and between sociodemographic factors, SN, and SS. Higher social status and more income were related to larger, more diverse networks and more SS. Higher social status and being married were related to more SS. Being married was related to more belonging and tangible support. Results show the complex relationship between higher level social factors and specific SS functions offering areas for future interventions to increase SS in heart patients.
Ginkgo biloba extract EGb® 761 exerts anti‐angiogenic effects via activation of tyrosine phosphatases
Authors: Koltermann Anja , Liebl Johanna , Fürst Robert , Ammer Hermann , Vollmar Angelika M. , Zahler Stefan
Published: July 2009

The standardised Ginkgo biloba extract EGb® 761 (Dr. Willmar Schwabe Pharmaceuticals, Karlsruhe, Germany) is one of the most widely used herbal remedies. Indications for this extract range from dementia to peripheral vascular disease, based on well‐documented vascular effects. Surprisingly, the actions of EGb® 761 on angiogenesis as a function of vascular cells have not been investigated to date. The anti‐cancer activity of EGb® 761 in vitro and epidemiological data showing reduced risk for ovarian cancer in regular users have prompted us to investigate this issue. We show an anti‐angiogenic profile of EGb® 761 in vitro (inhibited proliferation, migration and tube formation of endothelial cells) and in vivo in the chicken chorio‐allantoic membrane (CAM) assay. An analysis of the underlying mechanisms indicates inhibition of growth factor‐induced extracellular signal‐regulated kinase (ERK) phosphorylation by EGb® 761. Inhibitory effects of EGb® 761 on ERK as well as of the upstream kinases map‐erk‐kinase (MEK) and rapidly growing fibrosarcoma (Raf)‐1 could be completely reversed by pre‐treatment with sodium vanadate (inhibitor of tyrosine phosphatases). Sodium vanadate also reversed the EGb® 761‐induced inhibition of endothelial cell migration. Focusing on tyrosine phosphatases upstream of the Raf‐MEK‐ERK cascade, we identified the tyrosine phosphatase Src homology‐2 domain‐containing phosphatase 1 (SHP‐1) as one target of EGb® 761. SHP‐1 was rapidly activated by EGb® 761, and silencing SHP‐1 (siRNA) abrogated reduction of endothelial proliferation by EGb® 761. In summary, we identify EGb® 761 as a potent anti‐angiogenic drug. The underlying mechanism is the activation of protein tyrosine phosphatases, leading to inhibition of the Raf‐MEK‐ERK pathway. These findings provide a rational basis for using EGb® 761 for an additional therapeutic indication: anti‐angiogenesis‐based tumour prevention and adjuvant therapy.
Oncolytic virotherapy for advanced liver tumours
Authors: Chang Ju‐Fang , Chen Pei‐Jer , Sze Daniel Y. , Reid Tony , Bartlett David , Kirn David H. , Liu Ta‐Chiang
Published: July 2009

Introduction

Pre‐clinical studies

Clinical studies

Challenges for the use of virotherapy agents in liver tumour treatment

Future directions

Primary and metastatic neoplasms of the liver account for more than a million deaths per year worldwide. Despite decades of research, effective novel therapies for these cancers are urgently needed. Oncolytic virotherapeutics represent a novel class of pharmacophore that holds promise for the treatment of hepatic neoplasms. Cancer‐specific replication is followed by oncolysis, virus spreading and infection of adjacent cancer cells. This process is then repeated. Virotherapeutics target multiple genetic pathways involved in carcino‐genesis, and demonstrate activity against apoptosis‐resistant tumour cells. This platform can also exploit the advantage of multiple intrinsic anti‐cancer therapeutic mechanisms, combining direct viral oncolysis with therapeutic transgene expression. Recent advances in pre‐clinical and clinical studies are revealing the potential of this unique therapeutic class, in particular for liver cancers. This review summarizes the available data on applying oncolytic virotherapeutics to hepatic neoplasms to date, and discusses the challenges and future directions for virotherapy.
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

In 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

Unrestricted 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

It 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

Invadopodia 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

Mantle 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

Background:  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

Objectives:  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

Background  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

Question: 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.