bluuebunny/crossref_metadata_2025 huggingface dataset:
Cadmium induces Wnt signaling to upregulate proliferation and survival genes in sub-confluent kidney proximal tubule cells
Authors: Chakraborty Prabir K , Lee Wing-Kee , Molitor Malte , Wolff Natascha A , Thévenod Frank
Published: May 2010

Background

The class 1 carcinogen cadmium (Cd2+) disrupts the E-cadherin/β-catenin complex of epithelial adherens junctions (AJs) and causes renal cancer. Deregulation of E-cadherin adhesion and changes in Wnt/β-catenin signaling are known to contribute to carcinogenesis.

Results

We investigated Wnt signaling after Cd2+-induced E-cadherin disruption in sub-confluent cultured kidney proximal tubule cells (PTC). Cd2+ (25 μM, 3-9 h) caused nuclear translocation of β-catenin and triggered a Wnt response measured by TOPflash reporter assays. Cd2+ reduced the interaction of β-catenin with AJ components (E-cadherin, α-catenin) and increased binding to the transcription factor TCF4 of the Wnt pathway, which was upregulated and translocated to the nucleus. While Wnt target genes (c-Myc, cyclin D1 and ABCB1) were up-regulated by Cd2+, electromobility shift assays showed increased TCF4 binding to cyclin D1 and ABCB1 promoter sequences with Cd2+. Overexpression of wild-type and mutant TCF4 confirmed Cd2+-induced Wnt signaling. Wnt signaling elicited by Cd2+ was not observed in confluent non-proliferating cells, which showed increased E-cadherin expression. Overexpression of E-cadherin reduced Wnt signaling, PTC proliferation and Cd2+ toxicity. Cd2+ also induced reactive oxygen species dependent expression of the pro-apoptotic ER stress marker and Wnt suppressor CHOP/GADD153 which, however, did not abolish Wnt response and cell viability.

Conclusions

Cd2+ induces Wnt signaling in PTC. Hence, Cd2+ may facilitate carcinogenesis of PTC by promoting Wnt pathway-mediated proliferation and survival of pre-neoplastic cells.
A high-throughput transient gene expression system for switchgrass (Panicum virgatum L.) seedlings
Authors: Chen Xinlu , Equi Raymie , Baxter Holly , Berk Kyle , Han Jin , Agarwal Sujata , Zale Janice
Published: May 2010

Background

Grasses are relatively recalcitrant to genetic transformation in comparison to certain dicotyledons, yet they constitute some of the most important biofuel crops. Genetic transformation of switchgrass (Panicum virgatum L.) has previously been reported after cocultivation of explants with Agrobacterium and biolistics of embryogenic calli. Experiments to increase transient gene expression in planta may lead to stable transformation methods with increased efficiency.

Results

A high-throughput Agrobacterium-mediated transient gene expression system has been developed for in planta inoculation of germinating switchgrass seedlings. Four different Agrobacterium strains were compared for their ability to infect switchgrass seedlings, and strain AGL1 was found to be the most infective. Wounding pretreatments such as sonication, mixing by vortex with carborundum, separation by centrifugation, vacuum infiltration, and high temperature shock significantly increased transient expression of a reporter gene (GUSPlus, a variation of the β-glucuronidase (GUS) gene). The addition of L-cysteine and dithiothreitol in the presence of acetosyringone significantly increased GUS expression compared with control treatments, whereas the addition of 0.1% surfactants such as Silwet L77 or Li700 decreased GUS expression. 4-Methylumbelliferyl beta-D-galactopyranoside (MUG) assays showed a peak of β-glucuronidase (GUS) enzyme activity 3 days after cocultivation with Agrobacterium harboring pCambia1305.2, whereas MUG assays showed a peak of enzyme activity 5 days after cocultivation with Agrobacterium harboring pCambia1305.1.

Conclusion

Agrobacterium strains C58, GV3101 and EHA105 are less able to deliver transfer DNA to switchgrass seedlings (cultivar Alamo) compared with strain AGL1. Transient expression was increased by double or triple wounding treatments such as mixing by vortex with carborundum, sonication, separation by centrifugation, and heat shock. The addition of thiol compounds such as L-cysteine and dithiothreitol in combination with acetosyringone during cocultivation also increased transient expression. The combination of multiple wounding treatments along with the addition of thiol compounds during cocultivation increased transient expression levels from 6% to 54%. There were differences in temporal GUS expression induced by pCambia1305.1 and pCambia1305.2.
Proton pump inhibitors as anti vacuolar-ATPases drugs: a novel anticancer strategy
Authors: Spugnini Enrico P , Citro Gennaro , Fais Stefano
Published: May 2010

The vacuolar ATPases are ATP-dependent proton pumps whose functions include the acidification of intracellular compartments and the extrusion of protons through the cell cytoplasmic membrane. These pumps play a pivotal role in the regulation of cell pH in normal cells and, to a much greater extent, in tumor cells. In fact, the glucose metabolism in hypoxic conditions by the neoplasms leads to an intercellular pH drift towards acidity. The acid microenvironment is modulated through the over-expression of H+transporters that are also involved in tumor progression, invasiveness, distant spread and chemoresistance. Several strategies to block/downmodulate the efficiency of these transporters are currently being investigated. Among them, proton pump inhibitors have shown to successfully block the H+transporters in vitro and in vivo, leading to apoptotic death. Furthermore, their action seems to synergize with conventional chemotherapy protocols, leading to chemosensitization and reversal of chemoresistance. Aim of this article is to critically revise the current knowledge of this cellular machinery and to summarize the therapeutic strategies developed to counter this mechanism.
Human adenosine deaminase 2 induces differentiation of monocytes into macrophages and stimulates proliferation of T helper cells and macrophages
Authors: Zavialov Andrey V , Gracia Eduard , Glaichenhaus Nicolas , Franco Rafael , Zavialov Anton V , Lauvau Grégoire
Published: May 2010

Discovery of the growth factor activity of ADA2.

ADAs play a pivotal role in regulating the level of adenosine, a signaling molecule controlling a variety of cellular responses by binding to and activating four ADRs. Two enzymes, ADA1 and ADA2, are known to possess ADA activity in humans. Although the structure of ADA1 and its role in lymphocytic activation have been known for a long time, the structure and function of ADA2, a member of ADGF, remain enigmatic. Here, we found that ADA2 is secreted by monocytes undergoing differentiation into macrophages or DCs and that it binds to the cell surface via proteoglycans and ADRs. We demonstrate that ADA1 and ADA2 increase the rate of proliferation of monocyte-activated CD4+ T cells independently of their catalytic activity. We also show that ADA2 induces T cell-dependent differentiation of monocytes into macrophages and stimulates macrophage proliferation. Our discovery of the growth factor-like activity of ADA2 explains clinical observations and suggests that this enzyme could be used as a drug candidate to modulate the immune responses during inflammation and cancer.
T cell immunoglobulin- and mucin-domain-containing molecule-4 attenuates concanavalin A-induced hepatitis by regulating macrophage
Authors: Xu Liyun , Qi Jianni , Zhao Peiqing , Liang Xiaohong , Ju Ying , Liu Peng , Liu Bing , Guo Chun , Zhang Lining , Ma Chunhong , Gao Lifen
Published: May 2010

Tim-4 plays an important role in preventing liver injury through inhibition of CD80, CD86, and MHC II expression and TNF-α secretion by macrophages.

Tim-4 is expressed primarily on APCs, including macrophages, and has been shown to play a critical role in T cell regulation. However, it remains unclear whether Tim-4 also plays a role in the regulation of macrophage functions. In the present study, we investigated the effects of Tim-4 on macrophage activity in Con A-induced hepatitis in mice. We found that high levels of Tim-4 expression were associated with a diminished serum level of ALT in Con A-induced hepatitis. In addition, adoptive transfer of T4-RAW cells resulted in a significant decrease in ALT levels and Con A-induced liver injuries in mice. Concurrently, T4-RAW cells transfer displayed, markedly decreased apoptosis in liver and depressed TNF-α secretion in serum, supporting the hypothesis that Tim-4 protects Con A-induced hepatitis by negatively regulating macrophages. Consistent with the in vivo findings, in vitro studies showed that Tim-4 overexpression in RAW264.7 cells was associated with decreased expression of CD80, CD86, and MHCII molecules and the production of TNF-α. Moreover, Tim-4 blockade promoted LPS-induced macrophage activation. In conclusion, these findings indicate that Tim-4 plays an important role in alleviating liver damage by inhibition of macrophage activity. Tim-4 pathway could be a potential target for the treatment of acute hepatitis.
When Truces Collapse: A Longitudinal Study of Price-Adjustment Routines
Authors: Zbaracki Mark J. , Bergen Mark
Published: May 2010

We analyze the microfoundations of the routine in a study of price-adjustment processes at a manufacturing firm. Existing theory says that truces balance cognitive and motivational differences across functions, but there is scant evidence on how truces work. We show both stability and change in routines. For minor price adjustments, routines incorporate truces in stable but separate market interpretations by the sales and marketing groups. Major price changes put truces at risk, as latent conflict over information and interests becomes overt. The ensuing battle shows how interests, information, and truces are intertwined in performing the routine. Routines are not just stable entities, but adaptive performances that include conflict. We illustrate how our approach addresses fundamental problems such as how firms perform economics, how routines incorporate economic theory, and how routines shape macroeconomic dynamics. We argue that our approach can be extended to any routine-based organizational work.
Microfoundations of Internal and External Absorptive Capacity Routines
Authors: Lewin Arie Y. , Massini Silvia , Peeters Carine
Published: May 2010

The 20 years following the introduction of the seminal construct of absorptive capacity (AC) by Cohen and Levinthal (Cohen, W. M., D. A. Levinthal. 1989. Innovation and learning: The two faces of R&D. Econom. J. 99(397) 569–596; Cohen, W. M., D. A. Levinthal. 1990. Absorptive capacity: A new perspective on learning and innovation. Admin. Sci. Quart. 35(1) 128–152) have seen the proliferation of a vast literature citing the AC construct in over 10,000 published papers, chapters, and books, and interpreting it or applying it in many areas of organization science research, including organization theory, strategic management, and economics. However, with very few exceptions, the specific organizational routines and processes that constitute AC capabilities remain a black box. In this paper, we propose a routine-based model of AC as a first step toward the operationalization of the AC construct. Our intent is to direct attention to the importance of balancing internal knowledge creating processes with the identification, acquisition, and assimilation of new knowledge originating in the external environment. We decompose the construct of AC into two components, internal and external AC capabilities, and identify the configuration of metaroutines underlying these two components. These higher-level routines are expressed within organizations by configurations of empirically observable practiced routines that are idiosyncratic and firm specific. Therefore, we conceptualize metaroutines as the foundations of practiced routines. The ability of organizations to discover and implement complementarities between AC routines may explain why some firms are successful early adopters and most firms are imitators. Success as an early adopter of a new management practice or an innovation is expected to depend on the extent to which an organization evolves, adapts, and implements the configuration of its internal and external absorptive capacity routines.
Prior Alliances with Targets and Acquisition Performance in Knowledge-Intensive Industries
Authors: Zaheer Akbar , Hernandez Exequiel , Banerjee Sanjay
Published: May 2010

An important focus of the research on mergers and acquisitions is the conditions under which acquisitions create value for the acquiring firm's shareholders. Given that the acquisition process is plagued by serious issues of information asymmetry, which are exacerbated in the context of knowledge acquisitions, we examine whether prior alliances with potential targets reduce the information asymmetry enough to create “partner-specific absorptive capacity” and yield superior stock returns on acquisition, compared with acquisitions not preceded by alliances. We test our hypotheses on a sample of high-technology acquisitions by U.S. firms during 1990–1998 using an event study methodology to assess abnormal stock returns. We find, unexpectedly, that no significant general effect emerges for acquisitions with prior alliances. However, international acquisitions following alliances show significantly better returns relative to both acquisitions without prior alliances and domestic acquisitions. Additionally, stronger forms of prior alliances lead to better acquisition performance than weaker forms of alliances. Together, the results broadly support our thesis that partner-specific absorptive capacity may be at work and suggest that under certain prior alliance conditions, acquisitions can indeed create value for acquirers.
Vancomycin-Associated Uterine Contractions/Oxcarbazepine-Related Neutropenia/Atazanavir-Associated Choledocholithiasis/Zaleplon-Induced Amnestic Eating Disorder/Metoclopramide-Induced Encephalopathy in Parkinson's Disease/Clozapine-Induced Myocarditis
Authors: Shuster Joel
Published: May 2010

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers.
Is Aspirin Really Effective for Primary Cardiovascular Prevention?
Authors: Howard Patricia A.
Published: May 2010

Aspirin is widely used for the prevention of cardiovascular events. Although the evidence supporting the use of aspirin for secondary prevention is strong, its role in primary prevention in less clear. Nonetheless, recommendations from the US Preventive Services Task Force (USPSTF) continue to support the use of aspirin for primary cardiovascular prevention in select patients. This article will review current recommendations for primary prevention with aspirin, recent studies that have generated considerable controversy, and implications for clinical practice.
Promethazine Prescribing Patterns in Pediatric Inpatients Younger than Two Years before and after the Product Black Box Warning
Authors: Kessler Tiffany L. , Harrison Donald L. , Hagemann Tracy M.
Published: May 2010

Purpose

A black box warning was added to promethazine's labeling in November 2004 related to reports of respiratory depression in children younger than 2 years. The objective of this study was to determine what effect the changes in product labeling had on prescribing practices for promethazine at a pediatric hospital 1 year before (2004), 1 year immediately after (2005), and 2 years after (2006).

Methods

A retrospective chart review of orders for promethazine in pediatric inpatients (2 years and younger) admitted between 2004 and 2006 was conducted. Information collected included patient demographics and specifics about orders for promethazine (dose in mg/kg, route, indication, and number of as-needed doses received).

Results

A total of 255 orders for promethazine met study criteria. Though the number of promethazine orders decreased each year, there was no significant difference in promethazine use observed between 2004 and 2005 ( P = 0.223). However, a significant decrease in promethazine use occurred between 2005 and 2006 ( P = 0.017), a full year after the initial black box warning was released.

Conclusion

The black box warning has affected the prescribing patterns at a pediatric institution, causing a decrease in promethazine use. The response to the warning was slow for some services, which indicates a need for better communication and dissemination of prescribing information to medical staff and health care professionals.
New Drugs Approved by the FDA/New Dosage Forms and Indications Approved by the FDA/Agents Pending FDA Approval/Significant Labeling Changes or “Dear Health Professional” Letters Related to Safety
Authors: Baker Danial E.
Published: May 2010

This monthly feature will help readers keep current on new drugs, new indications, dosage forms, and safety-related changes in labeling or use. Efforts have been made to ensure the accuracy of this information
Evaluation of latent construct correlations in the presence of missing data: A note on a latent variable modelling approach
Authors: Raykov Tenko
Published: May 2010

A latent variable modelling approach is discussed, which can be used to evaluate indices of linear relationship between latent constructs in incomplete data sets. The method is based on an application of maximum‐likelihood estimation and inclusion of covariates predictive of missing values. The approach can be employed for point and interval estimation of latent correlations in the presence of missing data, and capitalizes on enhanced plausibility of the assumption of data missing at random through introduction of informative covariates. The method is illustrated on empirical data.
Variation in perceptions of physical dominance and trustworthiness predicts individual differences in the effect of relationship context on women's preferences for masculine pitch in men's voices
Authors: Vukovic Jovana , Jones Benedict C. , Feinberg David R. , DeBruine Lisa M. , Smith Finlay G. , Welling Lisa L. M. , Little Anthony C.
Published: May 2010

Several studies have found that women tend to demonstrate stronger preferences for masculine men as short‐term partners than as long‐term partners, though there is considerable variation among women in the magnitude of this effect. One possible source of this variation is individual differences in the extent to which women perceive masculine men to possess antisocial traits that are less costly in short‐term relationships than in long‐term relationships. Consistent with this proposal, here we show that the extent to which women report stronger preferences for men with low (i.e., masculine) voice pitch as short‐term partners than as long‐term partners is associated with the extent to which they attribute physical dominance and low trustworthiness to these masculine voices. Thus, our findings suggest that variation in the extent to which women attribute negative personality characteristics to masculine men predicts individual differences in the magnitude of the effect of relationship context on women's masculinity preferences, highlighting the importance of perceived personality attributions for individual differences in women's judgments of men's vocal attractiveness and, potentially, their mate preferences.
Confirmatory factor analysis and factorial invariance analysis of the adolescent self‐report Strengths and Difficulties Questionnaire: How important are method effects and minor factors?
Authors: van de Looij‐Jansen Petra M. , Goedhart Arnold W. , de Wilde Erik J. , Treffers Philip D. A.
Published: May 2010

Objectives. This study examined the factor structure of the self‐report Strengths and Difficulties Questionnaire, paying special attention to the number of factors and to negative effects of reverse‐worded items and minor factors within the subscales on model fit. Furthermore, factorial invariance across gender, age, level of education, and ethnicity was investigated.

Design. Data were obtained from the Youth Health Monitor Rotterdam, a community‐based health surveillance system.

Methods. The sample consisted of 11,881 pupils of 11–16 years old. Next to the original five‐factor model, a factor model with the number of factors based on parallel analysis and scree test was investigated. Confirmatory factor analysis for ordered‐categorical measures was applied to examine the goodness‐of‐fit and factorial invariance of the factor models.

Results. After allowing reverse‐worded items to cross‐load on the prosocial behaviour factor and adding error correlations, a good fit to the data was found for the original five‐factor model (emotional symptoms, conduct problems, hyperactivity–inattention, peer problems, prosocial behaviour) and a model with four factors (emotional symptoms and peer problems, conduct problems, hyperactivity–inattention, prosocial behaviour). Factorial invariance across gender, age, level of education, and ethnicity was found for the final five‐ and four‐factor model, except for the prosocial factor of the four‐factor model that showed partial invariance across gender.

Conclusions. While support was found for both models, the final five‐factor model is theoretically more plausible and gained additional support as the original scales emotional problems and peer problems showed different relations with gender, educational level, and ethnicity.
Investigating the relationship between trait and ability emotional intelligence and theory of mind
Authors: Qualter Pamela , Barlow Alexandra , Stylianou Maria S.
Published: May 2010

Theoretical links between emotional knowledge and theory of mind (ToM) have previously been proposed. This study investigates this relationship using measures of both ability and trait emotional intelligence (EI). Our sample comprised 194 children, divided into two age groups (5–7 years and 8–10 years). Children participated in measures of false belief understanding, advanced tests of ToM, ability EI and trait EI, and a standardized language assessment. For both age groups, we found that only ability EI was related to false belief understanding. Furthermore, regression analyses revealed that the understanding and managing branches of ability EI predicted unique variance in false belief understanding once controlling for age, language, and the other ability EI branches. Trait EI failed to display any association with false belief understanding. Ability and trait EI were associated with more advanced ToM tasks undertaken only by the older sample. These results offer support for previous research that has found a relationship between emotion perception and labelling and ToM. They also provide new knowledge: (1) higher order emotional knowledge, measured by ability EI, is associated with advanced ToM; and (2) emotional self efficacy, as measured by trait EI, is also important in advanced ToM. Furthermore, they provide the first account of associations between standardized EI measures and ToM.
Psychological vulnerabilities during police interviews. Why are they important?
Authors: Gudjonsson Gisli H.
Published: May 2010

Over the past three decades much has been learned about the role and importance of psychological vulnerabilities in the context of unreliability of information obtained during police interviews. This paper reviews the current state of knowledge and explains why vulnerabilities are important. Psychological vulnerabilities are best construed as potential ‘risk factors’ rather than definitive markers of unreliability. They are important, because they may place witnesses, victims, and suspects at a disadvantage in terms of coping with the demand characteristics of the interview (and subsequent Court process) and being able to provide the police with salient, detailed, accurate, and coherent answers to questions. Early identification of relevant and pertinent vulnerabilities in the interview process helps to ensure fairness and justice. Currently, the identification of vulnerabilities is poor, and even when identified, they are not always acted upon. Nevertheless, England has taken the lead in improving the police interview process and the protection of vulnerable interviewees. More work needs to be done, but the Bradley Report recommendations represent an excellent opportunity for police and health care professionals to work together to improve justice for all. This is the key initial interface that will be vital for reducing future miscarriages of justice.
Oligoclonal bands and immunoglobulin isotype switch during monitoring of patients with multiple myeloma and autologous hematopoietic cell transplantation: a 16-year experience
Authors: Alejandre Mariel Emilce , Madalena Leticia Bibiana , Pavlovsky Miguel Arturo , Facio Maria Laura , Corrado Claudia , Milone Gustavo , Bresciani Pablo Diego , Fraind Susana Alicia , Pavlovsky Santiago , Pizzolato Marco Antonio
Published: May 2010

Background: Over the last 20 years, high dose therapy followed by hemopoietic stem cell transplantation has been employed in patients with multiple myeloma (MM). During 16 years of follow-up, the degree of tumor response and survival in 238 patients with autologous stem cell transplantation (ASCT) and changes in the serum protein electrophoretic pattern were analyzed.

Methods: Agarose gel electrophoresis with densitometric analysis and immunofixation were performed to evaluate serum monoclonal protein. IgM, IgA, IgG and β2-microglobulin (β2M) were quantitated. Urine protein electrophoresis with IF was performed on cellulose acetate gel using colloidal silver staining without concentrating.

Results: After 34 months of follow-up (range 1–160 months), eight patients (3.4%) showed a distinct monoclonal protein band that was different from their original isotype switch. This was observed to be a transient phenomenon (22.2 months). Thirty-seven patients (15.5%) developed oligoclonal bands (OB) between the first and the twentieth month after ASCT (mean 4.4 months), which persisted for 7.9 months (1–36 months). The mean overall survival time was statistically different (p<0.05) between the group with OB and the group without them. Mean values of serum albumin, β2M, and non-involved immunoglobulins did not show statistical differences.

Conclusions: The occurrence of OB could be a potential favorable prognostic marker after transplantation due to the prolonged survival observed. Close follow-up of anomalous protein bands, either in serum or urine, is essential due to the additional difficulty in interpretation when the therapeutic response and evolution are evaluated.

Clin Chem Lab Med 2010;48:727–31.
Disasters: where they find us
Authors: Bersch Carren
Published: May 2010

Preparing for a natural disaster starts with a thorough understanding of the geography of your particular location, as well as its weather patterns. Early planning must also look beyond the disaster to examine the possible consequences of such a disaster. While no disaster/emergency preparedness planners like to think of the bleakest outcome (i.e., mass fatalities), building in solutions at the outset of a plan alleviates having to figure them out in the middle of an earthquake, a fire, or a hurricane. January's earthquake in Haiti holds lessons for anyone who is part of a first responder or healthcare profession, and those lessons have been hard ones for the world to learn.

Clin Chem Lab Med 2010;48:599–602.
Monographs on drugs which are frequently analyzed in therapeutic drug monitoring / Arzneimittel-Monographien für Medikamente, die regelmäßig im Rahmen des Therapeutic Drug Monitorings analysiert werden
Authors: Rentsch Working group “Drug Monitoring” of the SSCC: Katharina , Buhl Daniela , Eap Chin Bin , Fathi Marc , Jöchle Wolfgang , Magnin Jean-Luc , Thormann Wolfgang , Werner Dominique
Published: May 2010

In addition to the monographs which have been published in the past 4 years by the working group “Drug Monitoring” of the Swiss Society of Clinical Chemistry (SSCC) [1–4], new monographs have been written. The data presented in these monographs provide an overview of important information for the request and interpretation of results. Therefore, laboratory health professionals and the receivers of the reports are the targeted readers. In this series, several antiepileptic drugs are presented. Monographs on carbamazepine [1], lamotrigine [2], phenobarbital [2], and valproic acid [2] have been published previously. First, information about pharmacology and pharmacokinetics of these drugs (protein binding, metabolic pathways and enzymes involved, elimination half-life time and elimination route(s) of the parent drug and therapeutic as well as toxic concentrations) is given. Second, the indications for therapeutic drug monitoring are listed. Last but not least, important pre-analytical information is provided, including time points of blood sampling and time interval after which steady-state concentrations are reached after changing the dose. Furthermore, the stability of the drug and its metabolite(s) after blood sampling is described. For readers with a specific interest, references to important publications are given. The number of the monographs will be further enlarged. The updated files are presented on the homepage of the SSCC (www.sscc.ch). We hope that these monographs are helpful for the better handling of therapeutic drug monitoring and we are looking forward to comments from the readers.
Ein neues Antikoagulans zur Probengewinnung für Thrombozytenfunktionstests / A new anticoagulant for blood sampling tubes for platelet function tests
Authors: Wolf Johanna , Sigl Martin , Giannitsis Evangelos , Ivandic Boris
Published: May 2010

Hintergrund: Thrombozytenfunktionsdiagnostik, beispielsweise zum Nachweis einer Acetylsalicylsäure (ASS)- und/oder Clopidogrelresistenz wird immer häufiger nachgefragt, ist aber aufgrund der schwierigen Präanalytik wenig verbreitet. Bei der Blutentnahme und Probenaufbereitung können Aktivierungsprozesse in einer Citrat-antikoagulierten Probe nicht vollständig vermieden werden. Für den Einsatz zur Vollblutaggregometrie prüften wir ein neues Blutentnahmeröhrchen mit Benzylsulfonyl-D-Argininyl-Prolyl-4-Amidinobenzylamid (Xipla®) als Antikoagulans (Thrombovette®, Probe & go, Osburg) unter klinischen Routinebedingungen.

Methodik: Wir untersuchten 46 Patienten mit ASS- und Clopidogreltherapie aus der kardiologischen Notaufnahme sowie 20 gesunde Probanden. Die Blutentnahme erfolgte mit Thrombovette® und Citrat S-Monovette® (Sarstedt AG&Co, Nümbrecht). Nach Transport mit einem Rohrpostsystem wurde im Labor eine Vollblutaggregometrie mit Kollagen und ADP (Endkonzentrationen 1 mg/L bzw. 5 μM) mit einem Vollblut-Lumi-Aggregometer Modell 560Ca (Chrono-Log, Havertown, PA, USA) durchgeführt.

Ergebnisse: Anhand des Normalkollektivs wurden Referenzbereiche und Entscheidungsgrenzen (Mittelwert – 2-fache Standardabweichung) für das Vorliegen einer Resistenz ermittelt. Damit ergab sich zum Nachweis einer durch ASS gehemmten Aggregation mit Citrat S-Monovette® und Thrombovette® jeweils ein positiv prädiktiver Wert von über 94%. Zum Nachweis der Clopidogrelwirkung wurden mit Thrombovette® 68,0% und mit Citrat S-Monovette® 53,3% erhalten. Die negativ prädiktiven Werte zum Nachweis der ASS-Resistenz betrugen für die Citrat S-Monovette® und Thrombovette® 75% bzw. 82,8%, für den Nachweis der Clopidogrel-Resistenz wurden mit der Thrombovette® 87,8% und mit der Citrat S-Monovette 83,3% gefunden.

Schlussfolgerung: Die Thrombovette® ist ein Blutentnahmesystem, das eine verbesserte Validität der Thrombozytenfunktionsdiagnostik zum Nachweis einer ASS- und/oder Clopidogrel-Resistenz erwarten lässt.
Decreasing tumor size of thyroid cancer in Germany: institutional experience 1995–2009
Authors: Machens Andreas , Dralle Henning
Published: May 2010

Objective

Decreasing tumor size in a population over time is widely interpreted as a measure of effectiveness of cancer screening programs. Nonetheless, thyroid cancer size is rarely analyzed as a function of time. This study aimed to explore secular trends of thyroid cancer diameter in Germany.

Design

Retrospective analysis of 1644 thyroid cancer patients from a large referral center for thyroid cancer (1995–2009).

Methods

Calculation of largest tumor diameters for each type of cancer as a function of time periods and birth cohorts.

Results

Over the past 25 years, subdivided into 5-year periods by year of thyroidectomy (1985–1989; 1990–1994; 1995–1999; 2000–2004; 2005–2009), tumor diameters diminished from 25 to 16 mm (P=0.025) for medullary thyroid cancer and from 28 to 18 mm (P=0.017) for papillary thyroid cancer. This reduction was greater for hereditary medullary thyroid cancer (from 27 to 11 mm; P=0.088) than sporadic medullary thyroid cancer (from 23 to 19 mm; P=0.11). No decline was observed for follicular thyroid cancer (means of 45 to 42 mm; P=0.52). From the first (1921–1940) to the most recent birth cohort (1981–2000), tumor size fell from 22 to 10 mm (P<0.001) for medullary thyroid cancer, from 24 to 22 mm (P<0.001) for papillary thyroid cancer, and from 49 to 38 mm (P=0.011) for follicular thyroid cancer. The reduction of medullary thyroid cancers affected exclusively patients with hereditary disease (from 20 to 7 mm; P<0.001).

Conclusion

The consistency and robustness of these data signify powerful secular trends toward smaller papillary, follicular, and medullary thyroid cancers. The causes and consequences of these trends warrant further investigation.
A hypoechoic pattern of the thyroid at ultrasound does not indicate autoimmune thyroid diseases in patients with morbid obesity
Authors: Rotondi Mario , Cappelli Carlo , Leporati Paola , Chytiris Spyridon , Zerbini Francesca , Fonte Rodolfo , Magri Flavia , Castellano Maurizio , Chiovato Luca
Published: May 2010

Objective

Thyroid ultrasound (US) scan is a valuable tool for diagnosing thyroid diseases. In autoimmune thyroid disease (AITD), an hypoechoic pattern of the thyroid at US is related to circulating thyroid antibodies (Abs). The aim of this study was to evaluate the diagnostic accuracy of thyroid US for the detection of AITD in patients with morbid obesity.

Design

Thyroid US scans showing an hypoechoic pattern of the thyroid were collected from 105 morbid obese patients (body mass index (BMI) >40 kg/m2) and 105 non-obese patients (BMI≤30 kg/m2).

Results

A thyroid hypoechoic pattern at US was consistent with clinical/biochemical features of AITD in 90/105 (85.7%) non-obese patients and in 22/105 (20.9%) morbid-obese patients (P<0.0001). By performing a complete thyroid work-up, including clinical examination, thyroid morphology, serum hormones, and auto-Ab measurements, the discrepancy between the US pattern and the results of the thyroid Ab tests was justified in 6/15 non-obese patients, and only in 1/83 morbid obese patients. Thus, an unexplained hypoechoic pattern of the thyroid at US, defined as negative tests for thyroid Ab and absence of justifying thyroid disturbances, was found in 2/105 (1.9%) non-obese patients and in 68/105 (64.8%) morbid obese patients (P<0.0001).

Conclusions

Our results suggest that i) morbid obesity may affect thyroid morphology, and ii) an hypoechoic pattern of the thyroid at US, a well-established parameter for diagnosing AITD, has a poor diagnostic accuracy when patients with morbid obesity are taken into account.
Androgen profiles during pubertal Leydig cell development in mice
Authors: Wu Xiufeng , Arumugam Ramamani , Zhang Ningning , Lee Mary M
Published: May 2010

Postnatal Leydig cell (LC) development in mice has been assumed empirically to resemble that of rats, which have characteristic hormonal profiles at well-defined maturational stages. To characterize the changes in LC function and gene expression in mice, we examined reproductive hormone expression from birth to 180 days, and quantifiedin vivoandin vitroproduction of androgens during sexual maturation. Although the overall plasma androgen and LH profiles from birth through puberty were comparable to that of rats, the timing of developmental changes in androgen production and steroidogenic capacity of isolated LCs differed. In mice, onset of androgen biosynthetic capacity, distinguished by an acute rise in androstenedione and testosterone production and an increased expression of the steroidogenic enzymes, cytochrome P450 cholesterol side-chain cleavage enzyme and 17α-hydroxylase, occurred at day 24 (d24) rather than at d21 as reported in rats. Moreover, in contrast to persistently high testosterone production by pubertal and adult rat LCs, testosterone production was maximal at d45 in mice, and then declined in mature LCs. The murine LCs also respond more robustly to LH stimulation, with a greater increment in LH-stimulated testosterone production. Collectively, these data suggest that the mouse LC lineage has a delayed onset, and that it has an accelerated pace of maturation compared with the rat LC lineage. Across comparable maturational stages, LCs exhibit species-specific developmental changes in enzyme expression and capacity for androgen production. Our results demonstrate distinct differences in LC differentiation between mice and rats, and provide informative data for assessing reproductive phenotypes of recombinant mouse models.
Pregnancy-related changes in connections from the cervix to forebrain and hypothalamus in mice
Authors: Yellon Steven M , Grisham Lauren A , Rambau Genevieve M , Lechuga Thomas J , Kirby Michael A
Published: May 2010

The transneuronal tracer pseudorabies virus was used to test the hypothesis that connections from the cervix to the forebrain and hypothalamus are maintained with pregnancy. The virus was injected into the cervix of nonpregnant or pregnant mice, and, after 5 days, virus-labeled cells and fibers were found in specific forebrain regions and, most prominently, in portions of the hypothalamic paraventricular nucleus. With pregnancy, fewer neurons and fibers were evident in most brain regions compared to that in nonpregnant mice. In particular, little or no virus was found in the medial and ventral parvocellular subdivisions, anteroventral periventricular nucleus, or motor cortex in pregnant mice. By contrast, labeling of virus was sustained in the dorsal hypothalamus and suprachiasmatic nucleus in all groups. Based upon image analysis of digitized photomicrographs, the area with label in the rostral and medial parvocellular paraventricular nucleus and magnocellular subdivisions was significantly reduced in mice whose cervix was injected with virus during pregnancy than in nonpregnant mice. The findings indicate that connections from the cervix to brain regions that are involved in sensory input and integrative autonomic functions are reduced during pregnancy. The findings raise the possibility that remaining pathways from the cervix to the forebrain and hypothalamus may be important for control of pituitary neuroendocrine secretion, as well as for effector functions in the cervix as pregnancy nears term.
Endocrine complications in long-term survivors of childhood cancers
Authors: Chemaitilly Wassim , Sklar Charles A
Published: May 2010

Endocrine disturbances are among the most frequently reported complications in childhood cancer survivors, affecting between 20 and 50% of individuals who survive into adulthood. Most endocrine complications are the result of prior cancer treatments, especially radiotherapy. The objective of the present review is to discuss the main endocrine complications observed in this population, including disorders of the hypothalamic–pituitary axis, disorders of pubertal development, thyroid dysfunction, gonadal dysfunction, decreased bone mineral density, obesity, and alterations in glucose metabolism with a special focus on recent findings reported from the Childhood Cancer Survivor Study.
The anti-adipogenic effect of angiotensin II on human preadipose cells involves ERK1,2 activation and PPARG phosphorylation
Authors: Fuentes Paula , Acuña María José , Cifuentes Mariana , Rojas Cecilia V
Published: May 2010

Despite the importance of adipocyte formation for adipose tissue physiology, current knowledge about the mechanisms that regulate the recruitment of progenitor cells to undergo adipogenic differentiation is limited. A role for locally generated angiotensin II emerged from studies with human and murine cells. Preadipose cells from different human fat depots show reduced response to adipogenic stimuli when exposed to angiotensin II. This investigation sought to gain an insight into the intracellular mechanisms involved in the anti-adipogenic response of human preadipose cells from omental fat to angiotensin II. Its effect was evaluated on cells stimulated to adipogenic differentiation in vitro, by assessment of glycerol-3-phosphate dehydrogenase activity and expression of early markers of adipogenesis. Extracellular signal-regulated kinase1,2 (ERK1,2) pathway activation was inferred from the phosphorylated to total ERK1,2 ratio determined by western blot. Exposure to angiotensin II throughout the 10-day differentiation period resulted in a reduced adipogenic response. A similar anti-adipogenic effect was observed when this hormone was present during the first 48 h of induction to differentiation. Angiotensin II treatment had no consequences on CCAAT/enhancer-binding protein β and peroxisome proliferator-activated receptor γ (PPARG) induction, but increased the phosphorylated form of the key adipogenic regulator PPARG. Upon angiotensin II exposure, a raise of phosphorylated ERK1,2 was determined, which was more prominent 8–20 h after induction of adipogenesis (when controls reached negligible values). Chemical inhibition of ERK1,2 phosphorylation prevented angiotensin II-dependent reduction in adipogenesis. These results support the participation of the mitogen-activated protein kinase/ERK1,2 pathway in the anti-adipogenic effect of angiotensin II on preadipose cells from human omental adipose tissue.
Pancreatic islets of bank vole show signs of dysfunction after prolonged exposure to high glucose concentrations in vitro
Authors: Blixt Martin , Niklasson Bo , Sandler Stellan
Published: May 2010

Bank voles develop glucose intolerance/diabetes mellitus when kept in captivity. We have characterized β-cell function of glucose intolerant/diabetic animals, and found that this animal model has features of both human type 1 and type 2 diabetes. The aim of this study was to study the functional alterations of islets isolated from glucose tolerant bank voles after a prolonged exposure to various glucose concentrations in vitro. For this purpose, pancreatic islets from normal (glucose tolerant) male and female bank voles were cultured at different glucose concentrations (5.6, 11.1 (control), or 28 mM) whereupon islet functions were examined. Overall, islet insulin output was lowered at 5.6 mM glucose, and similar to control, or enhanced after culture in 28 mM glucose. High glucose culture led to decreased insulin contents, but there was no change in islet DNA content and in morphological assessments of cell death, with the latter findings suggesting that the so-called glucotoxicity had not evolved. A slight gender difference was observed in that islets isolated from females exhibited a glucose-regulated (pro)insulin biosynthesis rate and insulin gene expression. In conclusion, we have found that islets isolated from female and male bank voles are affected by glucose concentrations in vitro in that some signs of dysfunction were observed upon high glucose exposure. A minor gender difference was observed suggesting that the islets of the females may more readily adapt to the elevated glucose concentration than islets of the male bank voles. It could be that these in vitro gender differences observed may represent a mechanism underlying the gender difference in diabetes development observed among bank voles.
A 4‐Year Evaluation of the Peri‐Implant Parameters of Immediately Loaded Implants Placed in Fresh Extraction Sockets
Authors: Crespi Roberto , Capparè Paolo , Gherlone Enrico
Published: May 2010

Background: The present study considers the correlation between the meaning of keratinized mucosa (KM) and the long‐term maintenance of endosseous root‐form dental implants placed in fresh sockets and immediately loaded.

Methods: Twenty‐nine patients requiring extractions of ≥2 teeth in the maxilla and mandible were selected. One‐hundred thirty‐two maxillary and 32 mandibular teeth, in the incisor, canine, and premolar regions, were extracted. Implants were positioned in fresh sockets and immediately loaded. Based on the amounts of KM, implants were categorized as follows: KM ≥2 mm (group A) and KM <2 mm (group B). Clinical parameters (probing depth, modified plaque index, modified bleeding index, and gingival index) and marginal bone levels were followed at 4 years after implant placement. Comparisons between group A and B values were performed by the Student two‐tailed t test.

Results: At 4‐year follow‐up, a survival rate of 100% was reported for all implants. The mean values of group B were significantly higher (P <0.05) than group A for the following parameters: gingival index (group A, 0.67 ± 0.09; group B, 1.01 ± 0.11); modified plaque index (group A, 1.18 ± 0.09; group B, 1.71 ± 0.12); and modified bleeding index (group A, 0.35 ± 0.05; group B, 0.78 ± 0.05). Gingival recession was significantly elevated in group B. In both group A and group B, up to 60% of gingival recession occurred within the first 6 months. For mean bone loss values, statistically non‐significant differences were reported between groups.

Conclusions: At 4‐year follow‐up, the results suggested that the presence of mid‐buccal KM is not a critical factor in the maintenance of interproximal bone level around fresh socket implants immediately loaded. Conversely, less width of KM is significantly associated with more gingival inflammation, more plaque accumulation, and more gingival recession.
Screening to Identify Mental Health Problems in Pediatric Primary Care: Considerations for Practice
Authors: Brown Jonathan D. , Wissow Lawrence S.
Published: May 2010

Objective:

Few pediatric primary care providers routinely use mental health screening tools, in part because they may have concerns about whether screening is useful and how it will affect their practice. This study examined the extent to which screening in primary care would increase the identification of mental health problems among a diverse population of children and youth.

Methods:

Prior to the visit, the parents of 767 patients age 5 to 16 completed the Strengths and Difficulties Questionnaire to report their child's mental health symptoms and impairment. Without viewing the screening results, each child's provider ( N = 53) completed a questionnaire to report whether the child or youth demonstrated a mental health problem.

Results:

Compared with providers, the screen identified twice as many patients with moderate symptoms and nearly 28% more patients with high symptoms. Among patients with high symptoms, providers failed to identify a problem among 78% of those who were Latino/Other and 55% of those who were African American compared with 27% of Caucasian patients ( p < 0.001). Providers were not more likely to identify patients with externalizing versus internalizing symptoms but were more likely to identify patients who demonstrated symptoms across multiple domains of functioning.

Conclusions:

Screening substantially increased the number of children and youth who would be identified as possibly having a mental health problem. Screening may have the most potential to increase the identification of problems among patients who have moderate mental health symptoms and those who are African American or Latino.