bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-Level Laser Therapy Applied Transcranially to Rats After Induction of Stroke Significantly Reduces Long-Term Neurological Deficits
Authors: Oron Amir , Oron Uri , Chen Jieli , Eilam Anda , Zhang Chunling , Sadeh Menachem , Lampl Yair , Streeter Jackson , DeTaboada Luis , Chopp Michael
Published: September 2006

Background and Purpose—

Low-level laser therapy (LLLT) modulates various biological processes. In the present study, we assessed the hypothesis that LLLT after induction of stroke may have a beneficial effect on ischemic brain tissue.

Methods—

Two sets of experiments were performed. Stroke was induced in rats by (1) permanent occlusion of the middle cerebral artery through a craniotomy or (2) insertion of a filament. After induction of stroke, a battery of neurological and functional tests (neurological score, adhesive removal) was performed. Four and 24 hours poststroke, a Ga-As diode laser was used transcranially to illuminate the hemisphere contralateral to the stroke at a power density of 7.5 mW/cm
2
.

Results—

In both models of stroke, LLLT significantly reduced neurological deficits when applied 24 hours poststroke. Application of the laser at 4 hours poststroke did not affect the neurological outcome of the stroke-induced rats as compared with controls. There was no statistically significant difference in the stroke lesion area between control and laser-irradiated rats. The number of newly formed neuronal cells, assessed by double immunoreactivity to bromodeoxyuridine and tubulin isotype III as well as migrating cells (doublecortin immunoactivity), was significantly elevated in the subventricular zone of the hemisphere ipsilateral to the induction of stroke when treated by LLLT.

Conclusions—

Our data suggest that a noninvasive intervention of LLLT issued 24 hours after acute stroke may provide a significant functional benefit with an underlying mechanism possibly being induction of neurogenesis.
Blood Pressure Changes During the Initial Week After Different Subtypes of Ischemic Stroke
Authors: Toyoda Kazunori , Okada Yasushi , Fujimoto Shigeru , Hagiwara Noriko , Nakachi Koh , Kitazono Takanari , Ibayashi Setsuro , Iida Mitsuo
Published: September 2006

Background and Purpose—

The purpose of this study was to clarify the differences in the acute blood pressure course among different ischemic stroke subtypes.

Methods—

We divided 588 consecutive patients with acute brain infarction into four clinical subgroups to study the blood pressure levels during the initial 6 hospital days.

Results—

During the 6 days, systolic blood pressure of lacunar and atherothrombotic patients was higher (
P
=0.0001) and diastolic blood pressure of lacunar patients was higher (
P
=0.0371) than of patients with the other subtypes. Preexisting hypertension was associated with elevated acute systolic blood pressure in all patients and in each subtype and with elevated acute diastolic blood pressure in all patients, cardioembolic patients, and patients with stroke of other etiology. After adjustment by preexisting hypertension, diabetes mellitus with a hemoglobin A1c >7.0% was associated with elevated systolic blood pressure in all, lacunar, and cardioembolic patients and with diastolic blood pressure in all patients.

Conclusions—

Blood pressure course of patients sustaining acute stroke varied widely according to stroke subtypes. Poorly controlled diabetes mellitus, as well as preexisting hypertension, appeared to influence blood pressure during the initial week of stroke.
Preventing Parolees From Returning to Prison Through Community-Based Reintegration
Authors: Zhang Sheldon X. , Roberts Robert E. L. , Callanan Valerie J.
Published: September 2006

In the late 1990s, California legislators funded a statewide, community-based correctional program intended to reduce parolee recidivism. Overseen by the California Department of Corrections, the PreventingParolee Crime Program (PPCP) provided literacy training, employment services, housing assistance, and substance abuse treatment to tens of thousands of parolees. The study found that the PPCP produced modest reductions in reincarcerations and parole absconding, creating the potential for substantial long-term cost savings for California taxpayers. Because the PPCP's positive effects were strongest for parolees who completed their services, future program designers and administrators should consider including mechanisms to improve parolee retention and service utilization. This study also points out the potential benefits of incorporating rigorous evaluation plans into the design and implementation of correctional rehabilitation programs.
Neighborhood Residents' Production of Order: The Effects of Collective Efficacy on Responses to Neighborhood Problems
Authors: Wells William , Schafer Joseph A. , Varano Sean P. , Bynum Timothy S.
Published: September 2006

Community policing agencies seek to engage communities to build working partnerships, solicit the input of neighborhood residents, and stimulate informal control of crime. A common barrier to these efforts is a lack of citizen participation. The purpose of this article is to assess the relationship between neighborhood-level variables and citizen response to neighborhood problems. The authors'predictions are guided by recent research on collective efficacy and the relationship between neighborhood conditions and citizen actions. Accordingly, the authors expect neighborhood variables will affect residents'responses to perceived problems. Results show that residential-unit variables do not have significant effects on the likelihood that residents respond to neighborhood problems they identified. Methodological limitations must be overcome before it can be concluded that collective efficacy is not predictive of citizen responses to neighborhood problems, but research must consider this important outcome variable.
Long-Run Trends in Incarceration of Drug Offenders in the United States
Authors: Caulkins Jonathan P. , Chandler Sara
Published: September 2006

Estimates are developed for the number of people incarcerated in the United States for drug law violations between 1972 and 2002, broken down by type of institution (federal prison, state prison, or jail) and, to the extent possible, by nature of drug offense (possession or use, trafficking, or other). These time series are compared to trends in drug use indicators, revealing at best weak correlations, and the absolute levels are compared to different market indicators to draw various inferences. For example, even though about 480,000 people are incarcerated for drug law violations, on average retail sellers spend less than 2 hours behind bars per sale. Still, full-time sellers might expect to spend 3 months incarcerated per year of selling, suggesting that there are roughly four active drug sellers for every one who is incarcerated.
Violence Between the Police and the Public
Authors: Manzoni Patrik , Eisner Manuel
Published: September 2006

Stress of police officers is assumed to be one of the causes for an increased use of force, but to date, very few studies have tested this relationship empirically. This study examines influences of perceived work-related stress, job satisfaction, organizational commitment, and burnout on the use of force by police officers in Zurich, Switzerland ( n = 422). A new approach is developed by including the officer's routine activities (herein referred to as job profile) and victimization experiences as two situational controls and by capturing a continuum of self-reported force used in typical operational situations. Although bivariate results show significant relationships between use of force and work stress, job satisfaction, commitment, and burnout, multivariate analyses using structural equation models show no influence of stress-related factors on the amount of force. The job profile remains the only predictor of police use of force, whereas victimization is strongly correlated with use of force.
Treatment Response of Adolescent Offenders With Psychopathy Features
Authors: Caldwell Michael , Skeem Jennifer , Salekin Randy , Van Rybroek Gregory
Published: September 2006

This study examines the treatment response of 141 juvenile offenders with high scores on the Psychopathy Checklist:Youth Version ( M total > 27). Two groups of potentially psychopathic offenders are compared: one that participates in the Mendota Juvenile Treatment Center (MJTC), an intensive treatment program (MJTC, n = 56), and another that receives “treatment as usual” in conventional juvenile correctional institution (JCI) settings (JCI, n = 85). Offenders in the JCI group are more than twice as likely to violently recidivate in the community during a 2-year follow-up than those who participate in MJTC treatment. Treatment is associated with relatively slower and lower rates of serious recidivism, even after controlling for the effects of nonrandom assignment to treatment groups and release status. Implications for further research, treatment development, and juvenile justice issues are discussed.
Global Risk Indicators and the Role of Gender in a Juvenile Detention Sample
Authors: Gavazzi Stephen M. , Yarcheck Courtney M. , Chesney-Lind Meda
Published: September 2006

Growing evidence regarding the gender-specific nature of risk/needs factors in girls coming to the attention of the juvenile court is contrasted with the limited availability of gender-sensitive assessment instruments designed to measure risk/needs. In the present study, data are gathered from a sample of male and female youth assessed at a juvenile court detention facility. As hypothesized, analyses revealed significantly higher scores for males on prior offenses and significantly higher scores for females on family/parenting, mental health, traumatic events, and health-related risks. Unexpectedly, females also scored significantly higher than males in domains associated with psychopathy, accountability, and peer relationships. Female and male youth also differed in type of offense that brought them to the attention of the detention facility. In turn, type of offense was a predictor of risk/needs levels in the family/parenting domain, underscoring the particularly salient role family factors play in the lives of court-involved youth.
The Impact of Implicit Stereotyping on Offender Profiling
Authors: Dabney Dean A. , Dugan Laura , Topalli Volkan , Hollinger Richard C.
Published: September 2006

Much debate centers on the use of offender profiling as a technique to differentiate criminals from law-abiding citizens. Profiling advocates argue that it is appropriate to reference past experiences and information about known offenders to identify behavioral and demographic correlates that can then be applied to a given population of offenses or offenders. The viability of this argument rests on the assumption that past experiences and information about known offenders are free of bias. Data from an observational study of shoplifting are analyzed to assess this assumption systematically. Results indicate that trained observers, when allowed to deviate from a clearly specified random selection protocol, oversampled shoppers on the basis of race, gender, and perceived age, thus misrepresenting these factors as predictors of shoplifting behavior. Implications for the training of law enforcement and loss prevention officers are discussed.
Antidote Use in the Critically Ill Poisoned Patient
Authors: Betten David P. , Vohra Rais B. , Cook Matthew D. , Matteucci Michael J. , Clark Richard F.
Published: September 2006

The proper use of antidotes in the intensive care setting when combined with appropriate general supportive care may reduce the morbidity and mortality associated with severe poisonings. The more commonly used antidotes that may be encountered in the intensive care unit ( N-acetylcysteine, ethanol, fomepizole, physostigmine, naloxone, flumazenil, sodium bicarbonate, octreotide, pyridoxine, cyanide antidote kit, pralidoxime, atropine, digoxin immune Fab, glucagon, calcium gluconate and chloride, deferoxamine, phytonadione, botulism antitoxin, methylene blue, and Crotaline snake antivenom) are reviewed. Proper indications for their use and knowledge of the possible adverse effects accompanying antidotal therapy will allow the physician to appropriately manage the severely poisoned patient.
Critical Care of the Obstetric Patient
Authors: Shapiro Janet M.
Published: September 2006

The obstetric patient poses exceptional challenges in the intensive care unit. Knowledge of the physiologic changes of pregnancy and specific pregnancy-related disorders is necessary for optimal management. Intensive care unit diagnoses may include preeclampsia, including the HELLP syndrome, pulmonary embolic disease, amniotic fluid embolism, status asthmaticus, respiratory infection, the acute respiratory distress syndrome, and sepsis. The management of mechanical ventilation is based on principles of avoiding lung injury, and hypercapnia may be tolerated even during the pregnancy. When the clinician is faced with the extraordinary instance of cardiopulmonary arrest, perimortem cesarean delivery must be considered to improve the potential for maternal and fetal survival.
Obesity and Sepsis
Authors: Vachharajani Vidula , Vital Shantel
Published: September 2006

Obesity has reached epidemic proportions over the last few decades. Obesity is associated with increased morbidity and mortality in hypertension, cardiovascular diseases, stroke, and cancer and is feared to decrease overall life expectancy over the next few decades. There is a growing body of evidence suggesting that obesity is a chronic inflammatory disease. Obesity is becoming a cause of concern in critically ill patients as well. Sepsis is the number one cause of morbidity and mortality in noncoronary artery disease critical care units all over the world and is associated with a high cost of care. An increase in morbidity in obese septic patients compared with lean people is a cause of growing concern. Laboratory evidence suggests that there is exaggeration in the inflammatory and prothrombogenic phenotype assumed by obese compared with lean septic animals. The exact mechanisms underlying this phenomenon are unknown. This article reviews some of the pathophysiological processes responsible for the underlying inflammation in obesity and sepsis and reviews the literature for the association of the two.
Posttraumatic Stress Disorder in the Child of an Adult Burn Victim: A Case Report and Review of the Literature
Authors: Ceranoglu T. Atilla , Stern Theodore A.
Published: September 2006

Adults with a myriad of medical and surgical conditions are at risk for pain, delirium, and disfigurement. Needless to say, these critical illnesses are profoundly stressful for patients and their caregivers. However, physicians rarely consider the reactions of children to their parents’ illnesses. The article presents the case of a 15-year-old girl who developed posttraumatic stress disorder following her mother’s severe burn and complicated course in a critical care unit; the case is used to discuss strategies for the detection of psychological vulnerability and for the implementation of care. By learning more about the children of adult patients, by screening for interpersonal dysfunction, and by maximizing support systems, clinicians can improve function and minimize distress.
Acute Therapy of Maternal and Fetal Arrhythmias During Pregnancy
Authors: Trappe Hans-Joachim
Published: September 2006

Atrial premature beats are frequently diagnosed during pregnancy. Supraventricular tachycardia (atrial tachycardia, atrioventricular nodal reentrant tachycardia, circus movement tachycardia) is diagnosed less frequently. For acute therapy, electrical cardioversion with 50 to 100 J is indicated in all unstable patients. In stable supraventricular tachycardia, the initial therapy includes vagal maneuvers to terminate tachycardias. For short-term management, when vagal maneuvers fail, intravenous adenosine is the first choice drug and may safely terminate the arrhythmia. Ventricular premature beats are also frequently present during pregnancy and are benign in most patients; however, malignant ventricular tachyarrhythmias (sustained ventricular tachycardia, ventricular flutter, or ventricular fibrillation) may occur. Electrical cardioversion is necessary in all patients who are hemodynamically unstable with life-threatening ventricular tachyarrhythmias. In hemodynamically stable patients, initial therapy with ajmaline, procainamide, or lidocaine is indicated. In patients with syncopal ventricular tachycardia, ventricular fibrillation, ventricular flutter, or aborted sudden death, an implantable cardioverter-defibrillator is indicated. In patients with symptomatic bradycardia, a pacemaker can be implanted using echocardiography at any stage of pregnancy. The treatment of the pregnant patient with cardiac arrhythmias requires important modifications of the standard practice of arrhythmia management. The goal of therapy is to protect the patient and fetus through delivery, after which chronic or definitive therapy can be administered.
Mitochondrial DNA sequence variation in single cells from leukemia patients
Authors: Yao Yong-Gang , Ogasawara Yoji , Kajigaya Sachiko , Molldrem Jeffrey J. , Falcão Roberto P. , Pintão Maria-Carolina , McCoy J. Philip , Rizzatti Edgar Gil , Young Neal S.
Published: September 2006

A high frequency of mtDNA somatic mutation has been observed in many tumors as well as in aging tissues. In this study, we analyzed the mtDNA control region sequence variation in 3534 single normal cells and individual blasts from 18 patients with leukemia and 10 healthy donors, to address the mutation process in leukemic cells. We found significant differences in mtDNA sequence, as represented by the number of haplotypes and the mean number of cells with each nonaggregate haplotype in a population of cells, in patients compared to controls. Patients with similar clinical leukemia types, particularly acute myeloid leukemia (AML), did not show a uniform pattern of sequence variation in single blasts. Some patients at relapse presented a complex shift of major haplotypes in single cells. Four patients showed high frequencies of cells containing mutations 189, 260, 16150, and 16488, respectively, as a result of clonal expansion and could be considered as potential markers for their respective disease progression. To our knowledge, this is the first large-scale study of mtDNA variation in single malignant cells. Our results suggest that the somatic mutation process in leukemia is complex, leading to diverse levels of genetic alterations due to either intrinsic aspects of leukemia pathophysiology or chemotherapy effects.
Continuous in vivo infusion of interferon-gamma (IFN-γ) enhances engraftment of syngeneic wild-type cells in Fanca–/– and Fancg–/– mice
Authors: Si Yue , Ciccone Samantha , Yang Feng-Chun , Yuan Jin , Zeng Daisy , Chen Shi , van de Vrugt Henri J. , Critser John , Arwert Fre , Haneline Laura S. , Clapp D. Wade
Published: September 2006

Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow (BM) failure and cancer susceptibility. Identification of the cDNAs of FA complementation types allows the potential of using gene transfer technology to introduce functional cDNAs as transgenes into autologous stem cells and provide a cure for the BM failure in FA patients. However, strategies to enhance the mobilization, transduction, and engraftment of exogenous stem cells are required to optimize efficacy prior to widespread clinical use. Hypersensitivity of Fancc–/– cells to interferon-gamma (IFN-γ), a nongenotoxic immune-regulatory cytokine, enhances engraftment of syngeneic wild-type (WT) cells in Fancc–/– mice. However, whether this phenotype is of broad relevance in other FA complementation groups is unresolved. Here we show that primitive and mature myeloid progenitors in Fanca–/– and Fancg–/– mice are hypersensitive to IFN-γ and that in vivo infusion of IFN-γ at clinically relevant concentrations was sufficient to allow consistent long-term engraftment of isogenic WT repopulating stem cells. Given that FANCA, FANCC, and FANCG complementation groups account for more than 90% of all FA patients, these data provide evidence that IFN-γ conditioning may be a useful nongenotoxic strategy for myelopreparation in FA patients.
JAK2V617F: prevalence in a large Chinese hospital population
Authors: Xu Xuesong , Zhang Qi , Luo Jian , Xing Shu , Li Qingshan , Krantz Sanford B. , Fu Xueqi , Zhao Zhizhuang Joe
Published: September 2006

Recently, the JAK2V617F mutation was found in patients with myeloproliferative disorders (MPDs), including most with polycythemia vera (PV). The mutant JAK2 has increased kinase activity, and it was shown to be pathogenic in mouse models. Herein, we analyzed blood samples randomly collected from a clinical laboratory. Surprisingly, as many as 37 samples from a total of 3935 were found positive for the JAK2 mutation. However, only one of these samples had blood test results indicative for probable PV, but several had nonhematologic diseases. On average, samples with the mutation had normal red cell counts but significantly higher white blood cell and platelet counts, although most were within the normal range. The data suggest that the JAK2V617F mutation is apparently much more common than MPDs. Its occurrence may be a prelude to full blood cell abnormalities and other diseases, but it cannot by itself diagnose MPDs.
Role of phosphatidylinositol 3′-kinase/AKT pathway in diffuse large B-cell lymphoma survival
Authors: Uddin Shahab , Hussain Azhar R. , Siraj Abdul K. , Manogaran Pulicat S. , Al-Jomah Naif A. , Moorji Azadali , Atizado Valerie , Al-Dayel Fouad , Belgaumi Asim , El-Solh Hassan , Ezzat Adnan , Bavi Prashant , Al-Kuraya Khawla S.
Published: September 2006

Phosphatidylinositol 3′-kinase (PI3K) is a key player in cell-growth signaling in a number of lymphoid malignancies, but its role in diffuse large B-cell lymphoma (DLBCL) has not been fully elucidated. Therefore, we investigated the role of the PI3K/AKT pathway in a panel of 5 DLBCL cell lines and 100 clinical samples. Inhibition of PI3K by a specific inhibitor, LY294002, induced apoptosis in SUDHL4, SUDHL5, and SUDHL10 (LY-sensitive) cells, whereas SUDHL8 and OCI-LY19 (LY-resistant) cells were refractory to LY294002-induced apoptosis. AKT was phosphorylated in 5 of 5 DLBCL cell lines and inhibition of PI3K caused dephosphorylation/inactivation of constitutively active AKT, FOXO transcription factor, and GSK3 in LY-sensitive cell lines. In addition, there was a decrease in the expression level of inhibitory apoptotic protein, XIAP, in the DLBCL cell lines sensitive to LY294002 after treatment. However, no effect was observed in XIAP protein levels in the resistant DLBCL cell lines following LY294002 treatment. Finally, using immunohistochemistry, p-AKT was detected in 52% of DLBCL tumors tested. Furthermore, in univariate analysis, high p-AKT expression was associated with short survival. In multivariate analysis, this correlation was no longer significant. Altogether, these results suggest that the PI3K/AKT pathway may be a potential target for therapeutic intervention in DLBCL.
Long-term outcome of patients given transplants of mobilized blood or bone marrow: a report from the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation
Authors: Schmitz Norbert , Eapen Mary , Horowitz Mary M. , Zhang Mei-Jie , Klein John P. , Rizzo J. Douglas , Loberiza Fausto R. , Gratwohl Alois , Champlin Richard E.
Published: September 2006

We previously compared outcomes after allogeneic peripheral-blood stem cell (PBSC) and bone marrow (BM) transplantation in 706 patients with leukemia. We obtained long-term follow up on 413 of 491 patients who were alive at the time of the initial report: 141 PBSC and 272 BM recipients. Chronic graft-versus-host disease (GVHD) was more frequent after PBSC compared to BM transplantation (RR 1.65, P < .001) yet relapse rates were similar in both groups. Leukemia-free survival rates were higher after PBSC than BM transplantation for patients with advanced chronic myeloid leukemia (33% versus 25%) but lower for those in first chronic phase (41% versus 61%) due to higher rates of late transplant-related mortality. Leukemia-free survival was similar after PBSC and BM transplantation for acute leukemia. These data represent the early experience with PBSC grafts. Long-term outcomes in recipients of more recent transplants are required to better evaluate the role of PBSC grafts relative to BM transplantation.
WHIM syndrome myelokathexis reproduced in the NOD/SCID mouse xenotransplant model engrafted with healthy human stem cells transduced with C-terminus–truncated CXCR4
Authors: Kawai Toshinao , Choi Uimook , Cardwell Lanise , DeRavin Suk See , Naumann Nora , Whiting-Theobald Narda L. , Linton Gilda F. , Moon Jaehyun , Murphy Philip M. , Malech Harry L.
Published: September 2006

WHIM(warts, hypogammaglobulinemia, recurrent bacterial infection, and myelokathexis) syndrome is a rare immunodeficiency caused in many cases by autosomal dominant C-terminal truncation mutations in the chemokine receptor CXCR4. A prominent and unexplained feature of WHIM is myelokathexis (hypercellularity with apoptosis of mature myeloid cells in bone marrow and neutropenia). We transduced healthy human CD34+ peripheral blood–mobilized stem cells (PBSCs) with retrovirus vector encoding wild-type (wt) CXCR4 or WHIM-type mutated CXCR4 and studied these cells ex vivo in culture and after engraftment in a nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse xenograft model. Neither wt CXCR4 nor mutated CXCR4 transgene expression itself enhanced apoptosis of neutrophils arising in transduced PBSC cultures even with stimulation by a CXCR4 agonist, stromal cell–derived factor-1 (SDF-1 [CXCL12]). Excess wt CXCR4 expression by transduced human PBSCs enhanced marrow engraftment, but did not affect bone marrow (BM) apoptosis or the release of transduced leukocytes into PB. However, mutated CXCR4 transgene expression further enhanced BM engraftment, but was associated with a significant increase in apoptosis of transduced cells in BM and reduced release of transduced leukocytes into PB. We conclude that increased apoptosis of mature myeloid cells in WHIM is secondary to a failure of marrow release and progression to normal myeloid cell senescence, and not a direct effect of activation of mutated CXCR4.
Phosphotyrosine profiling identifies the KG-1 cell line as a model for the study of FGFR1 fusions in acute myeloid leukemia
Authors: Gu Ting-Lei , Goss Valerie L. , Reeves Cynthia , Popova Lana , Nardone Julie , MacNeill Joan , Walters Denise K. , Wang Yi , Rush John , Comb Michael J. , Druker Brian J. , Polakiewicz Roberto D.
Published: September 2006

The 8p11 myeloproliferative syndrome (EMS) is associated with translocations that disrupt the FGFR1 gene. To date, 8 fusion partners of FGFR1 have been identified. However, no primary leukemia cell lines were identified that contain any of these fusions. Here, we screened more than 40 acute myeloid leukemia cell lines for constitutive phosphorylation of STAT5 and applied an immunoaffinity profiling strategy to identify tyrosine-phosphorylated proteins in the KG-1 cell line. Mass spectrometry analysis of KG-1 cells revealed aberrant tyrosine phosphorylation of FGFR1. Subsequent analysis led to the identification of a fusion of the FGFR1OP2 gene to the FGFR1 gene. Small interfering RNA (siRNA) against FGFR1 specifically inhibited the growth and induced apoptosis of KG-1 cells. Thus, the KG-1 cell line provides an in vitro model for the study of FGFR1 fusions associated with leukemia and for the analysis of small molecule inhibitors against FGFR1 fusions.
STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation
Authors: Verga Falzacappa Maria Vittoria , Vujic Spasic Maja , Kessler Regina , Stolte Jens , Hentze Matthias W. , Muckenthaler Martina U.
Published: September 2006

Hepcidin is a key iron-regulatory hormone produced by the liver. Inappropriately low hepcidin levels cause iron overload, while increased hepcidin expression plays an important role in the anemia of inflammation (AI) by restricting intestinal iron absorption and macrophage iron release. Its expression is modulated in response to body iron stores, hypoxia, and inflammatory and infectious stimuli involving at least in part cytokines secreted by macrophages. In this study we established and characterized IL6-mediated hepcidin activation in the human liver cell line Huh7. We show that the proximal 165 bp of the hepcidin promoter is critical for hepcidin activation in response to exogenously administered IL6 or to conditioned medium from the monocyte/macrophage cell line THP-1. Importantly, we show that hepcidin activation by these stimuli requires a STAT3 binding motif located at position –64/–72 of the promoter. The same STAT binding site is also required for high basal-level hepcidin mRNA expression under control culture conditions, and siRNA-mediated RNA knockdown of STAT3 strongly reduces hepcidin mRNA expression. These results identify a missing link in the acute-phase activation of hepcidin and establish STAT3 as a key effector of baseline hepcidin expression and during inflammatory conditions.
Microarray identifies ADAM family members as key responders to TGF-β1 in alveolar epithelial cells
Authors: Keating Dominic T , Sadlier Denise M , Patricelli Andrea , Smith Sinead M , Walls Dermot , Egan Jim J , Doran Peter P
Published: September 2006

The molecular mechanisms of Idiopathic Pulmonary Fibrosis (IPF) remain elusive. Transforming Growth Factor beta 1(TGF-β1) is a key effector cytokine in the development of lung fibrosis. We used microarray and computational biology strategies to identify genes whose expression is significantly altered in alveolar epithelial cells (A549) in response to TGF-β1, IL-4 and IL-13 and Epstein Barr virus.

A549 cells were exposed to 10 ng/ml TGF-β1, IL-4 and IL-13 at serial time points. Total RNA was used for hybridisation to Affymetrix Human Genome U133A microarrays. Each in vitro time-point was studied in duplicate and an average RMA value computed. Expression data for each time point was compared to control and a signal log ratio of 0.6 or greater taken to identify significant differential regulation. Using normalised RMA values and unsupervised Average Linkage Hierarchical Cluster Analysis, a list of 312 extracellular matrix (ECM) proteins or modulators of matrix turnover was curated via Onto-Compare and Gene-Ontology (GO) databases for baited cluster analysis of ECM associated genes.

Interrogation of the dataset using ontological classification focused cluster analysis revealed coordinate differential expression of a large cohort of extracellular matrix associated genes. Of this grouping members of the ADAM (A disintegrin and Metalloproteinase domain containing) family of genes were differentially expressed. ADAM gene expression was also identified in EBV infected A549 cells as well as IL-13 and IL-4 stimulated cells. We probed pathologenomic activities (activation and functional activity) of ADAM19 and ADAMTS9 using siRNA and collagen assays. Knockdown of these genes resulted in diminished production of collagen in A549 cells exposed to TGF-β1, suggesting a potential role for these molecules in ECM accumulation in IPF.
A joint model of regulatory and metabolic networks
Authors: Yeang Chen-Hsiang , Vingron Martin
Published: September 2006

Background

Gene regulation and metabolic reactions are two primary activities of life. Although many works have been dedicated to study each system, the coupling between them is less well understood. To bridge this gap, we propose a joint model of gene regulation and metabolic reactions.

Results

We integrate regulatory and metabolic networks by adding links specifying the feedback control from the substrates of metabolic reactions to enzyme gene expressions. We adopt two alternative approaches to build those links: inferring the links between metabolites and transcription factors to fit the data or explicitly encoding the general hypotheses of feedback control as links between metabolites and enzyme expressions. A perturbation data is explained by paths in the joint network if the predicted response along the paths is consistent with the observed response. The consistency requirement for explaining the perturbation data imposes constraints on the attributes in the network such as the functions of links and the activities of paths. We build a probabilistic graphical model over the attributes to specify these constraints, and apply an inference algorithm to identify the attribute values which optimally explain the data. The inferred models allow us to 1) identify the feedback links between metabolites and regulators and their functions, 2) identify the active paths responsible for relaying perturbation effects, 3) computationally test the general hypotheses pertaining to the feedback control of enzyme expressions, 4) evaluate the advantage of an integrated model over separate systems.

Conclusion

The modeling results provide insight about the mechanisms of the coupling between the two systems and possible "design rules" pertaining to enzyme gene regulation. The model can be used to investigate the less well-probed systems and generate consistent hypotheses and predictions for further validation.
Analysis of the genome-wide variations among multiple strains of the plant pathogenic bacterium Xylella fastidiosa
Authors: Doddapaneni Harshavardhan , Yao Jiqiang , Lin Hong , Walker M Andrew , Civerolo Edwin L
Published: September 2006

Background

The Gram-negative, xylem-limited phytopathogenic bacterium Xylella fastidiosa is responsible for causing economically important diseases in grapevine, citrus and many other plant species. Despite its economic impact, relatively little is known about the genomic variations among strains isolated from different hosts and their influence on the population genetics of this pathogen. With the availability of genome sequence information for four strains, it is now possible to perform genome-wide analyses to identify and categorize such DNA variations and to understand their influence on strain functional divergence.

Results

There are 1,579 genes and 194 non-coding homologous sequences present in the genomes of all four strains, representing a 76. 2% conservation of the sequenced genome. About 60% of the X. fastidiosa unique sequences exist as tandem gene clusters of 6 or more genes. Multiple alignments identified 12,754 SNPs and 14,449 INDELs in the 1528 common genes and 20,779 SNPs and 10,075 INDELs in the 194 non-coding sequences. The average SNP frequency was 1.08 × 10-2 per base pair of DNA and the average INDEL frequency was 2.06 × 10-2 per base pair of DNA. On an average, 60.33% of the SNPs were synonymous type while 39.67% were non-synonymous type. The mutation frequency, primarily in the form of external INDELs was the main type of sequence variation. The relative similarity between the strains was discussed according to the INDEL and SNP differences. The number of genes unique to each strain were 60 (9a5c), 54 (Dixon), 83 (Ann1) and 9 (Temecula-1). A sub-set of the strain specific genes showed significant differences in terms of their codon usage and GC composition from the native genes suggesting their xenologous origin. Tandem repeat analysis of the genomic sequences of the four strains identified associations of repeat sequences with hypothetical and phage related functions.

Conclusion

INDELs and strain specific genes have been identified as the main source of variations among strains, with individual strains showing different rates of genome evolution. Based on these genome comparisons, it appears that the Pierce's disease strain Temecula-1 genome represents the ancestral genome of the X. fastidiosa. Results of this analysis are publicly available in the form of a web database.
The relationship between quality of research and citation frequency
Authors: Nieminen Pentti , Carpenter James , Rucker Gerta , Schumacher Martin
Published: September 2006

Background

Citation counts are often regarded as a measure of the utilization and contribution of published articles. The objective of this study is to assess whether statistical reporting and statistical errors in the analysis of the primary outcome are associated with the number of citations received.

Methods

We evaluated all original research articles published in 1996 in four psychiatric journals. The statistical and reporting quality of each paper was assessed and the number of citations received up to 2005 was obtained from the Web of Science database. We then examined whether the number of citations was associated with the quality of the statistical analysis and reporting.

Results

A total of 448 research papers were included in the citation analysis. Unclear or inadequate reporting of the research question and primary outcome were not statistically significantly associated with the citation counts. After adjusting for journal, extended description of statistical procedures had a positive effect on the number of citations received. Inappropriate statistical analysis did not affect the number of citations received. Adequate reporting of the primary research question, statistical methods and primary findings were all associated with the journal visibility and prestige.

Conclusion

In this cohort of published research, measures of reporting quality and appropriate statistical analysis were not associated with the number of citations. The journal in which a study is published appears to be as important as the statistical reporting quality in ensuring dissemination of published medical science.
Heparin (GAG-hed) inhibits LCR activity of Human Papillomavirus type 18 by decreasing AP1 binding
Authors: Villanueva Rita , Morales-Peza Néstor , Castelán-Sánchez Irma , García-Villa Enrique , Tapia Rocio , Cid-Arregui Ángel , García-Carrancá Alejandro , López-Bayghen Esther , Gariglio Patricio
Published: September 2006

Background

High risk HPVs are causative agents of anogenital cancers. Viral E6 and E7 genes are continuously expressed and are largely responsible for the oncogenic activity of these viruses. Transcription of the E6 and E7 genes is controlled by the viral Long Control Region (LCR), plus several cellular transcription factors including AP1 and the viral protein E2. Within the LCR, the binding and activity of the transcription factor AP1 represents a key regulatory event in maintaining E6/E7 gene expression and uncontrolled cell proliferation. Glycosaminoglycans (GAGs), such as heparin, can inhibit tumour growth; they have also shown antiviral effects and inhibition of AP1 transcriptional activity. The purpose of this study was to test the heparinoid GAG-hed, as a possible antiviral and antitumoral agent in an HPV18 positive HeLa cell line.

Methods

Usingin vivoandin vitroapproaches we tested GAG-hed effects on HeLa tumour cell growth, cell proliferation and on the expression of HPV18 E6/E7 oncogenes. GAG-hed effects on AP1 binding to HPV18-LCR-DNA were tested by EMSA.

Results

We were able to record the antitumoral effect of GAG-hedin vivoby using as a model tumours induced by injection of HeLa cells into athymic female mice. The antiviral effect of GAG-hed resulted in the inhibition of LCR activity and, consequently, the inhibition of E6 and E7 transcription. A specific diminishing of cell proliferation rates was observed in HeLa but not in HPV-free colorectal adenocarcinoma cells. Treated HeLa cells did not undergo apoptosis but the percentage of cells in G2/M phase of the cell cycle was increased. We also detected that GAG-hed prevents the binding of the transcription factor AP1 to the LCR.

Conclusion

Direct interaction of GAG-hed with the components of the AP1 complex and subsequent interference with its ability to correctly bind specific sites within the viral LCR may contribute to the inhibition of E6/E7 transcription and cell proliferation. Our data suggest that GAG-hed could have antitumoral and antiviral activity mainly by inhibiting AP1 binding to the HPV18-LCR.
Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity
Authors: Powell Ashley A , Akare Sandeep , Qi Wenqing , Herzer Pascal , Jean-Louis Samira , Feldman Rebecca A , Martinez Jesse D
Published: September 2006

Background

There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA.

Methods

To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis.

Results

We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth.

Conclusion

We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype.
Health status in the ambulance services: a systematic review
Authors: Sterud Tom , Ekeberg Øivind , Hem Erlend
Published: September 2006

Background

Researchers have become increasingly aware that ambulance personnel may be at risk of developing work-related health problems. This article systematically explores the literature on health problems and work-related and individual health predictors in the ambulance services.

Methods

We identified the relevant empirical literature by searching several electronic databases including Medline, EMBASE, PsychINFO, CINAHL, and ISI Web of Science. Other relevant sources were identified through reference lists and other relevant studies known by the research group.

Results

Forty-nine studies are included in this review. Our analysis shows that ambulance workers have a higher standardized mortality rate, higher level of fatal accidents, higher level of accident injuries and a higher standardized early retirement on medical grounds than the general working population and workers in other health occupations. Ambulance workers also seem to have more musculoskeletal problems than the general population. These conclusions are preliminary at present because each is based on a single study. More studies have addressed mental health problems. The prevalence of post-traumatic stress symptom caseness was > 20% in five of seven studies, and similarly high prevalence rates were reported for anxiety and general psychopathology in four of five studies. However, it is unclear whether ambulance personnel suffer from more mental health problems than the general working population.

Conclusion

Several indicators suggest that workers in the ambulance services experience more health problems than the general working population and workers in other health occupations. Several methodological challenges, such as small sample sizes, non-representative samples, and lack of comparisons with normative data limit the interpretation of many studies. More coordinated research and replication are needed to compare data across studies. We discuss some strategies for future research.
The evaluation of the factors that cause aggregation during recombinant expression in E. coli is simplified by the employment of an aggregation-sensitive reporter
Authors: Schultz Tina , Martinez Lucia , de Marco Ario
Published: September 2006

Background

The yields of soluble recombinant proteins expressed in bacteria are often low due to the tendency of the heterologous proteins to form aggregates. Therefore, aggregation reporters have been envisaged to simplify the comparison among different expression conditions and to speed up the identification of suitable protocols that improve the solubility. The probe we used is composed by an Ibp AB promoter specifically activated by protein aggregates fused to a sequence coding the β-galactosidase, the activity of which becomes, therefore, indicative of the aggregation degree.

Results

The collected data show that the probe is reliable in terms of reproducibility inside a range of experimental conditions and faster and more sensitive than the analysis methods based on SDS-PAGE and successive western blot.

The β-galactosidase probe was useful to identify which parameters could influence the aggregation of the model proteins and to set up an optimized expression protocol. The effect of growth temperature, induction modality, co-expression with molecular chaperones and addition of osmolytes on the accumulation of aggregates were evaluated following the β-galactosidase activity. Interestingly, a significant correlation was observed between estimated decreased aggregation and higher yields of soluble protein.

We also compared a set of expression vectors with various regulative features and found that the single characteristics, like promoter, copy number or polymerase, were not relevant for controlling the recombinant protein aggregation whilst the crucial factor resulted being the total expression rate of the system.

Conclusion

The aggregation reporter used in our experiments represents a useful tool to evaluate the different factors that can be modulated to optimize a recombinant expression protocol. Furthermore, the rapid estimation of the aggregation degree enables to discriminate this from other causes responsible for scarce recombinant yields.
Genital tuberculosis in a tamoxifen-treated postmenopausal woman with breast cancer and bloody vaginal discharge
Authors: Neonakis Ioannis , Mantadakis Elpis , Gitti Zoe , Mitrouska Ioanna , Manidakis Louis George , Maraki Sofia , Samonis George
Published: September 2006

Background

Female genital tuberculosis is an uncommon disease that is rarely diagnosed in developed countries.

Case presentation

A 61-year-old postmenopausal woman who had undergone surgery and treated with adjuvant chemotherapy for infiltrating ductal carcinoma of the breast five years ago, presented with bloody vaginal discharge, fatigue, weight loss, and low grade fevers at night for two months. Histological examination of the endometrium, done based on the suspicion of a second primary cancer due to the tamoxifen therapy, revealed a granulomatous reaction. Liquid and solid mycobacterial cultures of the tissues were performed. Although the acid fast staining was negative, the liquid culture was positive for Mycobacterium tuberculosis. Involvement of other systems was not detected. The patient was treated with a three-drug antituberculosis regimen for 9 months and recovered fully.

Conclusion

Female genital tuberculosis is a rare but curable disease that should be included in the differential diagnosis of women with menstrual problems. Early diagnosis is important and may prevent unnecessary invasive procedures for the patient.