bluuebunny/crossref_metadata_2025 huggingface dataset:
End-Stage Cardiac Disease as an Initial Presentation of Systemic Myopathies: Case Series and Literature Review
Authors: Katzberg Hans , Karamchandani Jason , So Yuen T. , Vogel Hannes , Wang Ching H.
Published: May 2010

Life-threatening cardiomyopathy is associated with certain systemic myopathies and usually presents as an end-stage progression of the disease. However, cardiac symptoms can sometimes precede muscle weakness. The authors reviewed medical records from 2003 to 2008 on patients attending their neuromuscular clinic and identified patients who initially presented with an end-stage cardiomyopathy and were later diagnosed with a specific muscle disease through muscle biopsy. They report 5 cases of children who initially presented with cardiomyopathies without neuromuscular symptoms. The cardiac symptoms were so severe that 4 of them required cardiac transplantation and 1 died prior to transplantation. Review of muscle pathology confirmed the diagnoses of Becker muscular dystrophy, myofibrillar myopathy, mitochondrial myopathy with cytochrome oxidase deficiency, Danon disease, and glycogen storage disease. The authors conclude that cardiomyopathy can be the initial presentation of a wide spectrum of systemic myopathies. Careful evaluation of neuromuscular systems should be carried out in patients presenting with end-stage cardiomyopathies.
Tectocerebellar Dysraphism With Vermian Encephalocele
Authors: Anik Ihsan , Koc Kenan , Anik Yonca , Yildiz Demir Kursat , Ceylan Savas
Published: May 2010

Tectocerebellar dysraphism is a very rare malformation associated with encephalocele and tectal deformity. This article presents tectocerebellar dysraphism with a solely vermian content of encephalocele and tectal beaking defined by magnetic resonance imaging (MRI) in a 5-month-old girl who was successfully treated surgically and demonstrated excellent prognosis at the 4-year follow-up.
Cerebellar Atrophy in Human and Murine Succinic Semialdehyde Dehydrogenase Deficiency
Authors: Acosta Maria T. , Munasinghe Jeeva , Pearl Phillip L. , Gupta Maneesh , Finegersh Andrey , Gibson K. Michael , Theodore William H.
Published: May 2010

Human succinic semialdehyde dehydrogenase deficiency, an autosomal recessive disorder of γ-aminobutyric acid (GABA) catabolism, was modeled by a murine model sharing the phenotype of ataxia and seizures. Magnetic resonance imaging (MRI) with volumetry was obtained on 7 patients versus controls, and MRI with stereology was derived in 3 murine genotypes: null, wild-type, and heterozygous mutants. All patients had T1 hypointensity and T2 hyperintensity in globus pallidus, and 5 also had similar changes in subthalamic and cerebellar dentate nuclei. There was a trend for patients to have a smaller cerebellar vermis. Homozygous null mice had significantly lower total brain and cerebellar volumes than wild-types and heterozygotes. Stereology confirmed cerebellar atrophy and was otherwise normal in multiple regions. Cerebellar volume loss is present in the murine disorder with a trend for cerebellar atrophy in patients. Reduced cerebellar volume can reflect neurodegeneration and may be related to the clinical manifestations.
A Novel Biocompatible Poly (3-hydroxy-co-4-hydroxybutyrate) Blend as a Potential Biomaterial for Tissue Engineering
Authors: Rao Urmila , Kumar Ramadhar , Balaji S. , Sehgal P.K.
Published: May 2010

Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) P(3HB-co-4HB) biopolymer was subjected to a depyrogenation treatment followed by blending with vitamin E (P(3HB-co-4HB)/Vit E blend), collagen (Col blend) or both (P(3HB-co-4HB)/Vit E/Col hybrid blend) to improve its biological performance. The cytocompatibility and pro-inflammatory response to the biopolymer after the treatment and blending were evaluated by cellular responses in vitro. Cell attachment and spreading of murine NIH 3T3 fibroblasts seeded on the films were found to be the highest on the hybrid P(3HB-co-4HB)/Vit E/Col blend film. The P(3HB-co-4HB) blends showed increased cell proliferation and negligible cytotoxicity. The pro-inflammatory cytokines, IL6 and TNF α expression in the murine macrophage cell line J774 A-1 monocyte/macrophage cells cultured on the biopolymer films were assessed by immunoblotting and RT-PCR analyses which revealed that the combined blending strategy was the most effective in reducing the pro-inflammatory activity. The depyrogenated P(3HB-co-4HB) blends significantly extend the range of biomaterials suitable for tissue engineering.
Pancreatitis Associated With Strongyloides stercoralis Infection in a Patient Chronically Treated With Corticosteroids
Authors: Jones Nathan , Cocchiarella Andrew , Faris Khaldoun , Heard Stephen O.
Published: May 2010

Strongyloides stercoralis is a nematode that is a ubiquitous parasite in man. Life-threatening infections can occur in immunocompromised patients. We report a case of a 64-year-old Puerto Rican gentleman treated chronically with corticosteroids for reactive airway disease, who presented to our institution with pancreatitis complicated by sepsis and acute lung injury requiring mechanical ventilation. The initial working diagnosis was gallstone pancreatitis; however, several days into his hospital course, he was found to have a history of strongyloidiasis. Subsequent examination of his stool revealed the parasite, and the patient was treated with ivermectin. This case highlights the occasional association between pancreatitis and strongyloidiasis and the importance of proper treatment and consideration of infection in patients from endemic regions, which include Central America, Africa, and Asia.
The Impact of a ‘‘Low-Intensity’’ Versus ‘‘High-Intensity’’ Medical Intensive Care Unit on Patient Outcomes in Critically Ill Veterans
Authors: Singer Jonathan P. , Kohlwes Jeffrey , Bent Stephen , Zimmerman Leslie , Eisner Mark D.
Published: May 2010

Objective: To determine whether a low-intensity versus high-intensity medical intensive care unit (MICU) format in a Veterans Affairs (VA) hospital setting improves patient outcomes, as measured by duration of mechanical ventilation (MV), ventilator-free days (VFDs), and hospital mortality. Design: Retrospective cohort study. Setting: Medical intensive care unit at the San Francisco Veterans Affairs Medical Center (SFVAMC). Patients: On July 1, 2004, the SFVAMC transitioned from a low-intensity MICU to a high-intensity MICU. All patients admitted to the MICU who required MV for 18 months before (n = 96) and 18 months after (n = 131) the transition were included in the analysis. Measurements: We prospectively defined the primary outcome measure as the difference in the median duration of MV between groups. Secondary outcomes included VFDs and hospital mortality. Continuous variables were compared using the Wilcoxon rank sum test; dichotomous variables were compared using Fisher exact test. Main results: The low-intensity and high-intensity MICU groups were similar in age, gender, weight, and admitting diagnosis (P > .27 in all cases). Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were 22.0 in the low-intensity era and 20.0 in the high-intensity era (P = .048). Median duration of MV was significantly lower in the high-intensity MICU format compared to the low-intensity MICU format (102 vs 61 hours, P for log-rank test = .0052). After controlling for covariates, there were 4.2 more VFDs in the high-intensity era (95% CI 1.9 to 6.6 days). The high-intensity era was associated with a reduced hospital mortality rate (27% vs 40%) and an adjusted odds ratio of 0.34 (95% CI 0.15 to 0.74). Conclusions: For critically ill veterans admitted to an MICU requiring MV, a high-intensity ICU structure is associated with more favorable mechanical ventilatory outcomes and lower mortality.
Simple Melanosis of the Bladder: A Rare Entity
Authors: Talmon Geoffrey A. , Khan Ansar U. , Koerber Rodney K. , Johansson Sonny L.
Published: May 2010

Simple melanosis of the bladder is an uncommon condition with fewer than 15 reported cases characterized by multifocal, diffuse melanin pigmentation of the urothelial mucosa. It is frequently associated with urinary incontinence or urgency. Histologically, melanin granules are present within urothelial cells or lamina propria macrophages with or without bland-appearing mucosal melanocytes. Although considered a benign entity, the rarity of the lesion warrants regular follow-up cystoscopic evaluation with biopsies to screen for the development of malignancy, especially malignant melanoma. This study presents a “typical” case with light, cytochemical, immunohistochemical, and ultrastructural characterization.
Lymphoepithelioma-Like Carcinoma of the Ovary
Authors: Ambrosio Maria Raffaella , Rocca Bruno Jim , Onorati Monica , Mourmouras Vasileios , Mastrogiulio Maria Grazia , Crispino Sergio , Liberatore Concetta , Santopietro Rosa
Published: May 2010

Only one case of lymphoepithelioma-like carcinoma of the ovary has been reported so far. A new case is herein illustrated in a 69-year-old woman: an ovarian mass adherent to urinary bladder dome with peritoneal carcinomatosis. Histologically, undifferentiated carcinomatous areas were intermingled with abundant lymphoid tissue. Epstein-Barr virus has not been detected either in neoplastic or in lymphoid cells.
A 4-Week Intrathecal Toxicity and Pharmacokinetic Study With Trastuzumab in Cynomolgus Monkeys
Authors: Braen Angélique P. J. M. , Perron Josée , Tellier Pierre , Catala Anthony R. , Kolaitis Gerry , Geng Wanping
Published: May 2010

Trastuzumab is indicated for the treatment of patients with breast cancer overexpressing human epidermal growth factor 2 (HER2). Women with HER2-positive tumors have an increased risk of brain metastases. The blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier may prevent trastuzumab from reaching appropriate concentrations in the brain and CSF following standard intravenous administration. To evaluate the potential of effects on the central nervous system, a 4-week toxicology study with weekly intrathecal administration of trastuzumab was performed in cynomolgus monkeys at doses of 0, 3, or 15 mg. No trastuzumab-related effects on body weight, clinical signs, neurological function, clinical pathology, or anatomic pathology were noted. The applied doses and CSF concentrations achieved in the current study exceeded those reported in patients after intrathecal administration. The results support future studies for further evaluation of intrathecal application of trastuzumab in patients with brain metastases in HER2-positive breast cancer.
Arsenic Exposure In Utero and Nonepidermal Proliferative Response in Adulthood in Tg.AC Mice
Authors: Tokar Erik J. , Diwan Bhalchandra A. , Waalkes Michael P.
Published: May 2010

To expand our knowledge on the transplacental carcinogenic potential of inorganic arsenic, pregnant Tg.AC mice received drinking water with 0, 42.5, or 85 ppm arsenite from gestation day 8 to 18. After birth, groups (n = 25) of offspring received topical 12- O-tetradecanoyl phorbol-13-acetate (TPA) (2 μg twice a week) for 36 weeks and were killed; nonskin tumors were assessed. Arsenic increased adrenal cortical adenomas (ACAs; 25%-29%) compared with control (0%) independent of TPA in all male groups. Arsenic increased urinary bladder (UB) hyperplasia in males, but only with TPA. Arsenic induced ACAs in all female groups (control 0%; arsenic 17%-26%). Arsenic-treated females had UB hyperplasia in most groups (control 0%; arsenic 26%-32%), with 2 UB papillomas. All arsenic-treated females had uterine hyperplasia (26%-40%; control 4%) independent of TPA, and 3 had uterine tumors. Thus, arsenic in utero rapidly induces ACAs and uterine and UB preneoplasias in Tg.AC mice, showing transplacental carcinogenic potential in yet another strain of mice.
Defining Hormesis: Evaluation of a Complex Concentration Response Phenomenon
Authors: Kendig Eric L. , Le Hoa H. , Belcher Scott M.
Published: May 2010

Hormesis describes dose-response relationships characterized by a reversal of response between low and high doses of chemicals, biological molecules, physical stressors, or other initiators of a response. Acceptance of hormesis as a viable dose-response theory has been limited until recently, in part, because of poor conceptual understanding, ad hoc and inappropriate use, and lack of a defined mechanism. By examining the history of this dose-response theory, it is clear that both pharmacological and toxicological studies provide evidence for hormetic dose responses, but retrospective examination of studies can be problematic at best. Limited scientific evidence and lack of a common lexicon with which to describe these responses have left hormesis open to inappropriate application to unrelated dose-response relationships. Future studies should examine low-dose effects using unbiased, descriptive criteria to further the scientific understanding of this dose response. A clear, concise definition is required to further the limited scientific evidence for hormetic dose responses.
Cellular Proliferation, Cell Death, and Liver Histology in Gambusia affinis After Dietary Exposure to Benzidine and 2-Aminofluorene
Authors: Lentz Susan , Eversole Rob , McHugh Law J. , Means Jay C.
Published: May 2010

Chronic exposure to arylamines through diet and/or smoking has been associated with genetic changes and tumorigenesis. Cellular proliferation, apoptosis, and histological changes in liver tissue were investigated in Gambusia affinis ( G affinis) after chronic dietary exposure to 6.9 mM and 0.069 mM concentrations of benzidine (BZ), 2-aminofluorene (2AF), and their combination for 4, 8, and 12 weeks, respectively. The proliferation assay indicated non–dose-dependent increases in cellular proliferation over the controls for all treatment groups at 4 and 12 weeks but not at 8 weeks except for the low dose of 2AF. The apoptosis assay showed effects in the low-dose group of 2AF and BZ at 4 weeks only. Hematoxylin/eosin staining of liver tissue revealed an increase in oval/spindle cell proliferation and altered foci formation in the treated groups compared with controls. These results demonstrate a mammalian-like response to 2AF and BZ in G affinis liver.
Final Report on the Safety Assessment of Sodium Cetearyl Sulfate and Related Alkyl Sulfates as Used in Cosmetics
Authors: Fiume Monice , Bergfeld Wilma F. , Belsito Donald V. , Klaassen Curtis D. , Marks James G. , Shank Ronald C. , Slaga Thomas J. , Snyder Paul W. , Andersen F. Alan
Published: May 2010

Sodium cetearyl sulfate is the sodium salt of a mixture of cetyl and stearyl sulfate. The other ingredients in this safety assessment are also alkyl salts, including ammonium coco-sulfate, ammonium myristyl sulfate, magnesium coco-sulfate, sodium cetyl sulfate, sodium coco/hydrogenated tallow sulfate, sodium coco-sulfate, sodium decyl sulfate, sodium ethylhexyl sulfate, sodium myristyl sulfate, sodium oleyl sulfate, sodium stearyl sulfate, sodium tallow sulfate, sodium tridecyl sulfate, and zinc coco-sulfate. These ingredients are surfactants used at concentrations from 0.1% to 29%, primarily in soaps and shampoos. Many of these ingredients are not in current use. The Cosmetic Ingredient Review (CIR) Expert Panel previously completed a safety assessment of sodium and ammonium lauryl sulfate. The data available for sodium lauryl sulfate and ammonium lauryl sulfate provide sufficient basis for concluding that sodium cetearyl sulfate and related alkyl sulfates are safe in the practices of use and concentration described in the safety assessment.
Neurobehavioral Effects of Acute Exposure to Aromatic Hydrocarbons
Authors: McKee Richard H. , Lammers J. H. C. M. , Muijser H. , Owen D. E. , Kulig B. M.
Published: May 2010

This article reports the results of neurobehavioral tests on representative aromatic constituents, specifically C9 to C11 species. The testing evaluated effects in several domains including clinical effects, motor activity, functional observations, and visual discrimination performance. Exposures ranging from 600 to 5000 mg/m3, depending on the molecular weights of the specific aromatic constituents, produced minor, reversible effects on the central nervous system (CNS), particularly in the domains of gait and visual discrimination. There was little evidence of effects at lower exposure levels. There was some evidence of respiratory effects at 5000 mg/m3 in 1 study, and there were also minor changes in body weight and temperature. The CNS effects became less pronounced with repeated exposures, corresponding to lower concentrations in the brain of 1 representative substance, 1,2,4-trimethyl benzene (TMB). At high exposure levels, the alkyl benzenes apparently induced their own metabolism, increasing elimination rates.
Cyclosporine A Attenuates 3-Nitropropionic Acid–Induced Huntington-Like Symptoms in Rats: Possible Nitric Oxide Mechanism
Authors: Kumar Puneet , Kalonia Harikesh , Kumar Anil
Published: May 2010

Cyclosporine A is a well-known immunosuppressant drug that is currently used for prevention of allograft rejection. The current study was conducted to explore the therapeutic potential of cyclosporine A against 3-nitropropionic acid (3-NP)–induced neurotoxicity, an animal model of Huntington disease (HD). Systemic administration of 3-NP (10 mg/kg) for 14 days significantly impaired body weight, motor activity, biochemical parameters (raised lipid peroxidation, nitrite concentration, depletion of superoxide dismutase [SOD] and catalase), and mitochondrial enzymes. Cyclosporine A (2.5, 5, and 10 mg/kg) treatment significantly attenuated behavioral, biochemical, and cellular alterations. Furthermore, l-arginine pretreatment with cyclosporine A (5 mg/kg) significantly reversed the protective effect of cyclosporine A. However, l-nitro-arginine methyl ester (l-NAME; 10 mg/kg) pretreatment potentiated the protective effect of cyclosporine A (5 mg/kg). Study highlights the therapeutic potential of cyclosporine A in the treatment of HP. Study suggests that nitric oxide (NO) modulation is involved in the neuroprotective effect of cyclosporine A against 3-NP neurotoxicity.
Exploring the role of spirituality in self-management practices among older African-American and non-Hispanic White women with chronic conditions
Authors: Shevon Harvey Idethia , Cook Lawanda
Published: May 2010

Objective: The purpose of this study was to examine the role of spirituality in the self-management of chronic illness among older women with chronic conditions.

Methods: A sample of 41 African-American and non-Hispanic White women, of age 66 and older, participated in the process of self-care study. Data were collected from semi-structured interviews and analysed for common themes using the Grounded Theory method.

Results: Audiotaped and transcribed interviews identified four categories that emerged to suggest the influence of spirituality in behavioural change and disease management: (1) God’s involvement in illness management; (2) prayer as a mediator; (3) spirituality as a coping mechanism; and (4) the combination of conventional and spiritual practices.

Discussion: Older women with various chronic illnesses defined ‘spirituality’ in a broad, holistic way, and the findings suggest that spirituality played a part in documenting the self-management process. Knowledge of spirituality and the role it plays in illness management may assist public health gerontologists in designing effective and culturally appropriate self-management programmes.
Gender differences and clustering pattern of behavioural risk factors for chronic non-communicable diseases: community-based study from a developing country
Authors: Ali Khan Khuwaja  , Muhammad Masood Kadir
Published: May 2010

Objectives: This study estimates the burden of behavioural risk factors for chronic non-communicable diseases (CNDs) to evaluate the degree of clustering and the differential of these factors by gender in adults.

Methods: In a community-based survey, information was obtained about behavioural risk factors for CNDs among 534 adults in Karachi, Pakistan. Chi-square test and odds ratio (OR) with 95% confidence interval (CI) were calculated to evaluate the differences of these factors by gender.

Results: Overall, 22.5% of adults had anxiety/depression, 47.8% did not have adequate intake of fruits and vegetables, 60.1% were physically inactive while 49.8% were overweight/obese. More women had anxiety/ depression (OR = 2.1; 95% CI = 1.4—3.1), were physically inactive (OR=2.1; 95% CI = 1.5—3.1) and overweight/ obese (OR= 6.2; 95% CI = 4.3—9.1). On the contrary, greater number of men were found to have inadequate fruit and vegetable consumption (OR = 1.8; 95% CI = 1.3—2.5). Only 1.1% of study subjects had none of the studied risk factors, 16.9% had one while 82% had ≥2 factors. The clustering of these risk factors was significantly higher in women (p<0.001).

Discussion: This study shows that almost all of the adults in the study had behavioural risk factors for CNDs and clustering of these factors is very common and significantly higher in women. The tendency of clustering risk factors in individuals provides opportunities to address factors with integrated approaches to prevent/delay the onset of CNDs.
Bringing self-management into clinical view: a qualitative study of long-term condition management in primary care consultations
Authors: Blakeman Tom , Bower Peter , Reeves David , Chew-Graham Carolyn
Published: May 2010

Objectives: To understand social processes underpinning support for self-management of long-term conditions in primary care.

Methods: Comparative analysis of observational and interview data concerning the management of long-term conditions in UK primary-care consultations. Analysis of recordings of primary care consultations (n = 86) was conducted in conjunction with analysis of semi-structured interviews with health professionals (n = 17) and patients (n = 12) living with a long-term condition.

Results: A key finding was the infrequency with which self-management topics became legitimate objects for discussion in consultations. Analysis suggested that the maintenance of self—other relations was a prime objective for both patients and professionals, and the introduction of self-management topics threatened this process. Technology and the division of labour among primary-care professionals reinforced this tension.

Discussion: In order for self-management support to become embedded and integrated into primary care, interventions concerning long-term condition management need to take into account this tension underpinning care.
Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma
Authors: Waage Anders , Gimsing Peter , Fayers Peter , Abildgaard Niels , Ahlberg Lucia , Björkstrand Bo , Carlson Kristina , Dahl Inger Marie , Forsberg Karin , Gulbrandsen Nina , Haukås Einar , Hjertner Øyvind , Hjorth Martin , Karlsson Torbjörn , Knudsen Lene Meldgaard , Nielsen Johan Lanng , Linder Olle , Mellqvist Ulf-Henrik , Nesthus Ingerid , Rolke Jürgen , Strandberg Maria , Sørbø Jon Hjalmar , Wisløff Finn , Juliusson Gunnar , Turesson Ingemar ,   for the Nordic Myeloma Study Group
Published: May 2010

In this double-blind, placebo-controlled study, 363 patients with untreated multiple myeloma were randomized to receive either melphalan-prednisone and thalidomide (MPT) or melphalan-prednisone and placebo (MP). The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days every 6 weeks until plateau phase. The dose of thalidomide/placebo was escalated to 400 mg daily until plateau phase and thereafter reduced to 200 mg daily until progression. A total of 357 patients were analyzed. Partial response was 34% and 33%, and very good partial response or better was 23% and 7% in the MPT and MP arms, respectively (P < .001). There was no significant difference in progression-free or overall survival, with median survival being 29 months in the MPT arm and 32 months in the MP arm. Most quality of life outcomes improved equally in both arms, apart from constipation, which was markedly increased in the MPT arm. Constipation, neuropathy, nonneuropathy neurologic toxicity, and skin reactions were significantly more frequent in the MPT arm. The number of thromboembolic events was equal in the 2 treatment arms. In conclusion, MPT had a significant antimyeloma effect, but this did not translate into improved survival. This trial was registered at www.clinicaltrials.gov as #NCT00218855.
BISMA - Fast and accurate bisulfite sequencing data analysis of individual clones from unique and repetitive sequences
Authors: Rohde Christian , Zhang Yingying , Reinhardt Richard , Jeltsch Albert
Published: May 2010

Background

Bisulfite sequencing is a popular method to analyze DNA methylation patterns at high resolution. A region of interest is targeted by PCR and about 20-50 subcloned DNA molecules are usually analyzed, to determine the methylation status at single CpG sites and molecule resolution.

Results

The BISMA (Bisulfite Sequencing DNA Methylation Analysis) software for analysis of primary bisulfite sequencing data implements sequencing data extraction and enhanced data processing, quality controls, analysis and presentation of the methylation state. It uses an improved strategy for detection of clonal molecules and accurate CpG site detection and it supports for the first time analysis of repetitive sequences.

Conclusions

BISMA works highly automated but still provides the user full control over all steps of the analysis. The BISMA software is freely available as an online tool for academic purposes for the analysis of bisulfite sequencing data from both unique and repetitive sequences http://biochem.jacobs-university.de/BDPC/BISMA/.
WD-repeat instability and diversification of the Podospora anserina hnwd non-self recognition gene family
Authors: Chevanne Damien , Saupe Sven J , Clavé Corinne , Paoletti Mathieu
Published: May 2010

Background

Genes involved in non-self recognition and host defence are typically capable of rapid diversification and exploit specialized genetic mechanism to that end. Fungi display a non-self recognition phenomenon termed heterokaryon incompatibility that operates when cells of unlike genotype fuse and leads to the cell death of the fusion cell. In the fungus Podospora anserina, three genes controlling this allorecognition process het-d, het-e and het-r are paralogs belonging to the same hnwd gene family. HNWD proteins are STAND proteins (signal transduction NTPase with multiple domains) that display a WD-repeat domain controlling recognition specificity. Based on genomic sequence analysis of different P. anserina isolates, it was established that repeat regions of all members of the gene family are extremely polymorphic and undergoing concerted evolution arguing for frequent recombination within and between family members.

Results

Herein, we directly analyzed the genetic instability and diversification of this allorecognition gene family. We have constituted a collection of 143 spontaneous mutants of the het-R (HNWD2) and het-E (hnwd5) genes with altered recognition specificities. The vast majority of the mutants present rearrangements in the repeat arrays with deletions, duplications and other modifications as well as creation of novel repeat unit variants.

Conclusions

We investigate the extreme genetic instability of these genes and provide a direct illustration of the diversification strategy of this eukaryotic allorecognition gene family.
Effects of phosphodiesterase 4 inhibition on bleomycin-induced pulmonary fibrosis in mice
Authors: Udalov Sergey , Dumitrascu Rio , Pullamsetti Soni S , Al-tamari Hamza M , Weissmann Norbert , Ghofrani Hossein A , Guenther Andreas , Voswinckel Robert , Seeger Werner , Grimminger Friedrich , Schermuly Ralph T
Published: May 2010

Background

Pulmonary fibrosis (PF) is a group of devastating and largely irreversible diseases. Phosphodiesterase (PDE) 4 is involved in the processes of remodeling and inflammation, which play key role in tissue fibrosis. The aim of the study was, therefore, to investigate the effect of PDE4 inhibition in experimental model of PF.

Methods

PF was induced in C57BL/6N mice by instillation of bleomycin. Pharmacological inhibition of PDE4 was achieved by using cilomilast, a selective PDE4 inhibitor. Changes in either lung inflammation or remodeling were evaluated at different stages of experimental PF. Lung inflammation was assessed by bronchoalveolar lavage fluid (BALF) differential cell count and reverse transcription quantitative polymerase chain reaction (RT-qPCR) for inflammatory cytokines. Changes in tissue remodeling were evaluated by pulmonary compliance measurement, quantified pathological examination, measurement of collagen deposition and RT-qPCR for late remodeling markers. Survival in all groups was analyzed as well.

Results

PDE4 inhibition significantly reduced the total number of alveolar inflammatory cells in BALF of mice with bleomycin-induced PF at early fibrosis stage (days 4 and 7). Number of macrophages and lymphocytes, but not neutrophils, was significantly reduced as well. Treatment decreased lung tumor necrosis factor (TNF)-α mRNA level and increased mRNA level of interleukin (IL)-6 but did not influence IL-1β. At later stage (days 14 and 24) cilomilast improved lung function, which was shown by increase in lung compliance. It also lowered fibrosis degree, as was shown by quantified pathological examination of Hematoxilin-Eosin stained lung sections. Cilomilast had no significant effect on the expression of late remodeling markers such as transforming growth factor (TGF)-β1 and collagen type Ia1 (COL(I)α1). However, it tended to restore the level of lung collagen, assessed by SIRCOL assay and Masson's trichrome staining, and to improve the overall survival.

Conclusions

Selective PDE4 inhibition suppresses early inflammatory stage and attenuates the late stage of experimental pulmonary fibrosis.
Degradation or excretion of quantum dots in mouse embryonic stem cells
Authors: Pi Qing Meng , Zhang Wen Jie , Zhou Guang Dong , Liu Wei , Cao Yilin
Published: May 2010

Background

Quantum dots (QDs) have been considered as a new and efficient probe for labeling cells non-invasively in vitro and in vivo, but fairly little is known about how QDs are eliminated from cells after labeling. The purpose of this study is to investigate the metabolism of QDs in different type of cells.

Results

Mouse embryonic stem cells (ESCs) and mouse embryonic fibroblasts (MEFs) were labeled with QD 655. QD-labeling was monitored by fluorescence microscopy and flow cytometry for 72 hours. Both types of cells were labeled efficiently, but a quick loss of QD-labeling in ESCs was observed within 48 hours, which was not prevented by inhibiting cell proliferation. Transmission electron microscope analysis showed a dramatic decrease of QD number in vesicles of ESCs at 24 hours post-labeling, suggesting that QDs might be degraded. In addition, supernatants collected from labeled ESCs in culture were used to label cells again, indicating that some QDs were excreted from cells.

Conclusion

This is the first study to demonstrate that the metabolism of QDs in different type of cells is different. QDs were quickly degraded or excreted from ESCs after labeling.
HSF1 overexpression enhances oncolytic effect of replicative adenovirus
Authors: Wang Cheng , Dai Zhehao , Fan Rong , Deng Youwen , Lv Guohua , Lu Guangxiu
Published: May 2010

Background

E1B55kD deleted oncolytic adenovirus was designed to achieve cancer-specific cytotoxicity, but showed limitations in clinical study. To find a method to increase its efficacy, we investigated the correlation between oncolytic effect of such oncolytic adenovirus Adel55 and intracellular heat shock transcription factor 1 (HSF1) activity.

Methods

In the present study, human breast cancer cell line Bcap37 was stably transfected with constitutively active HSF1 (cHSF1) or HSF1 specific siRNA (HSF1i) to establish increased or decreased HSF1 expression levels. Cytotoxicity of Adel55 was analyzed in these cell lines in vitro and in vivo. Furthermore, Adel55 incorporated with cHSF1 (Adel55-cHSF1) was used to treat various tumor xenografts.

Results

Adel55 could achieve more efficient oncolysis in cHSF1 transfected Bcap37 cells, both in vitro and in vivo. However, inhibition of HSF1 expression by HSF1i could rescue Bcap37 cell line from oncolysis by Adel55. A time course study of viral replication established a correlation between higher replication of Adel55 and cytolysis or tumor growth inhibition. Then, we constructed Adel55-cHSF1 for tumor gene therapy and demonstrated that it is more potent than Adel55 itself in oncolysis and replication in both Bcap37 and SW620 xenografts.

Conclusions

cHSF1 enhances the Adel55 cell-killing potential through increasing the viral replication and is a potential therapeutic implication to augment the potential of E1B55kD deleted oncolytic adenovirus by increasing its burst.
NR2 Subunits and NMDA Receptors on Lamina II Inhibitory and Excitatory Interneurons of the Mouse Dorsal Horn
Authors: Shiokawa Hiroaki , Kaftan Edward J , MacDermott Amy B , Tong Chi-Kun
Published: May 2010

Background:

NMDA receptors expressed by spinal cord neurons in the superficial dorsal horn are involved in the development of chronic pain associated with inflammation and nerve injury. The superficial dorsal horn has a complex and still poorly understood circuitry that is mainly populated by inhibitory and excitatory interneurons. Little is known about how NMDA receptor subunit composition, and therefore pharmacology and voltage dependence, varies with neuronal cell type. NMDA receptors are typically composed of two NR1 subunits and two of four NR2 subunits, NR2A-2D. We took advantage of the differences in Mg2+sensitivity of the NMDA receptor subtypes together with subtype preferring antagonists to identify the NR2 subunit composition of NMDA receptors expressed on lamina II inhibitory and excitatory interneurons. To distinguish between excitatory and inhibitory interneurons, we used transgenic mice expressing enhanced green fluorescent protein driven by the GAD67 promoter.

Results:

Analysis of conductance ratio and selective antagonists showed that lamina II GABAergic interneurons express both the NR2A/B containing Mg2+sensitive receptors and the NR2C/D containing NMDA receptors with less Mg2+sensitivity. In contrast, excitatory lamina II interneurons express primarily NR2A/B containing receptors. Despite this clear difference in NMDA receptor subunit expression in the two neuronal populations, focally stimulated synaptic input is mediated exclusively by NR2A and 2B containing receptors in both neuronal populations.

Conclusions:

Stronger expression of NMDA receptors with NR2C/D subunits by inhibitory interneurons compared to excitatory interneurons may provide a mechanism to selectively increase activity of inhibitory neurons during intense excitatory drive that can provide inhibitory feedback.
Duodenal gangliocytic paraganglioma showing lymph node metastasis: A rare case report
Authors: Okubo Yoichiro , Yokose Tomoyuki , Tuchiya Masaru , Mituda Aki , Wakayama Megumi , Hasegawa Chikako , Sasai Daisuke , Nemoto Tetsuo , Shibuya Kazutoshi
Published: May 2010

We describe a case of duodenal gangliocytic paraganglioma showing lymph node metastasis. A 61-year-old Japanese man underwent pylorus preserving pancreaticoduodenectomy to remove a tumor at the papilla of Vater. The section of the tumor extending from the mucosa to submucosa of the duodenum was sharply demarcated, solid, and white-yellowish. Neither necrosis nor hemorrhage was present. Histological examination confirmed the immunohistochemical identification of three components comprising epithelioid cells, spindle-shaped cells, and ganglion-like cells. Epithelioid cells showed positive reactivity for synaptophysin, somatostatin, and CD56. In contrast, spindle-shaped cells showed positive reactivity for S-100 protein, but not for synaptophysin, somatostatin or CD56. Furthermore, we found lymph node metastasis despite lack of bcl-2 and p53 expression. In addition to the rarity of the tumor, we are describing here the present case suggests the malignant potency of the tumor despite lack of acceptable prognostic indicators for neuroendocrine tumor.
FGF dependent regulation of Zfhx1b gene expression promotes the formation of definitive neural stem cells in the mouse anterior neurectoderm
Authors: Dang Lan TH , Tropepe Vincent
Published: May 2010

Background

Mouse definitive neural stem cells (NSCs) are derived from a population of LIF-responsive primitive neural stem cells (pNSCs) within the neurectoderm, yet details on the early signaling and transcriptional mechanisms that control this lineage transition are lacking. Here we tested whether FGF and Wnt signaling pathways can regulate Zfhx1b expression to control early neural stem cell development.

Results

By microinjecting FGF8b into the pro-amniotic cavity ex vivo at 7.0 days post-coitum (dpc) and culturing whole embryos, we demonstrate that neurectoderm-specific gene expression (for example, Sox2, Nestin, Zfhx1b) is increased, whereas Wnt3a represses neurectoderm gene expression. To determine whether FGF signaling also mediates the lineage transition from a pNSC to a NSC, 7.0-dpc embryos were microinjected with either FGF8b or inhibitors of the FGF receptor-MAP kinase signaling pathway ex vivo, cultured as whole embryos to approximately 8.5 dpc and assayed for clonal NSC colony formation. We show that pre-activation of FGF signaling in the anterior neurectoderm causes an increase in the number of colony forming NSCs derived later from the anterior neural plate, whereas inhibition of FGF signaling significantly reduces the number of NSC colonies. Interestingly, inhibition of FGF signaling causes the persistence of LIF-responsive pNSCs within the anterior neural plate and over-expression of Zfhx1b in these cells is sufficient to rescue the transition from a LIF-responsive pNSC to an FGF-responsive NSC.

Conclusion

Our data suggest that definitive NSC fate specification in the mouse neurectoderm is facilitated by FGF activation of Zfhx1b.
Spatio-temporal modeling of signaling protein recruitment to EGFR
Authors: Hsieh Ming-yu , Yang Shujie , Raymond-Stinz Mary Ann , Edwards Jeremy S , Wilson Bridget S
Published: May 2010

Background

A stochastic simulator was implemented to study EGFR signal initiation in 3D with single molecule detail. The model considers previously unexplored contributions to receptor-adaptor coupling, such as receptor clustering and diffusive properties of both receptors and binding partners. The agent-based and rule-based approach permits consideration of combinatorial complexity, a problem associated with multiple phosphorylation sites and the potential for simultaneous binding of adaptors.

Results

The model was used to simulate recruitment of four different signaling molecules (Grb2, PLCγ1, Stat5, Shc) to the phosphorylated EGFR tail, with rules based on coarse-grained prediction of spatial constraints. Parameters were derived in part from quantitative immunoblotting, immunoprecipitation and electron microscopy data. Results demonstrate that receptor clustering increases the efficiency of individual adaptor retainment on activated EGFR, an effect that is overridden if crowding is imposed by receptor overexpression. Simultaneous docking of multiple proteins is highly dependent on receptor-adaptor stability and independent of clustering.

Conclusions

Overall, we propose that receptor density, reaction kinetics and membrane spatial organization all contribute to signaling efficiency and influence the carcinogenesis process.
High-resolution genomic and expression analyses of copy number alterations in HER2-amplified breast cancer
Authors: Staaf Johan , Jönsson Göran , Ringnér Markus , Vallon-Christersson Johan , Grabau Dorthe , Arason Adalgeir , Gunnarsson Haukur , Agnarsson Bjarni A , Malmström Per-Olof , Johannsson Oskar Th , Loman Niklas , Barkardottir Rosa B , Borg Åke
Published: May 2010

Introduction

HER2 gene amplification and protein overexpression (HER2+) define a clinically challenging subgroup of breast cancer with variable prognosis and response to therapy. Although gene expression profiling has identified an ERBB2 molecular subtype of breast cancer, it is clear that HER2+ tumors reside in all molecular subtypes and represent a genomically and biologically heterogeneous group, needed to be further characterized in large sample sets.

Methods

Genome-wide DNA copy number profiling, using bacterial artificial chromosome (BAC) array comparative genomic hybridization (aCGH), and global gene expression profiling were performed on 200 and 87 HER2+ tumors, respectively. Genomic Identification of Significant Targets in Cancer (GISTIC) was used to identify significant copy number alterations (CNAs) in HER2+ tumors, which were related to a set of 554 non-HER2 amplified (HER2-) breast tumors. High-resolution oligonucleotide aCGH was used to delineate the 17q12-q21 region in high detail.

Results

The HER2-amplicon was narrowed to an 85.92 kbp region including the TCAP, PNMT, PERLD1, HER2, C17orf37 and GRB7 genes, and higher HER2 copy numbers indicated worse prognosis. In 31% of HER2+ tumors the amplicon extended to TOP2A, defining a subgroup of HER2+ breast cancer associated with estrogen receptor-positive status and with a trend of better survival than HER2+ breast cancers with deleted (18%) or neutral TOP2A (51%). HER2+ tumors were clearly distinguished from HER2- tumors by the presence of recurrent high-level amplifications and firestorm patterns on chromosome 17q. While there was no significant difference between HER2+ and HER2- tumors regarding the incidence of other recurrent high-level amplifications, differences in the co-amplification pattern were observed, as shown by the almost mutually exclusive occurrence of 8p12, 11q13 and 20q13 amplification in HER2+ tumors. GISTIC analysis identified 117 significant CNAs across all autosomes. Supervised analyses revealed: (1) significant CNAs separating HER2+ tumors stratified by clinical variables, and (2) CNAs separating HER2+ from HER2- tumors.

Conclusions

We have performed a comprehensive survey of CNAs in HER2+ breast tumors, pinpointing significant genomic alterations including both known and potentially novel therapeutic targets. Our analysis sheds further light on the genomically complex and heterogeneous nature of HER2+ tumors in relation to other subgroups of breast cancer.
An overview of seismic azimuth for towed streamers
Authors: Long Andrew
Published: May 2010

Conventional 3D streamer seismic processing generally ignores any azimuth component in the data. We are used to the convenience of acquiring overlapping shot gathers in straight lines, as we can sort the data into common midpoint gathers, and then exploit the power of stack in processing to attenuate random noise. The higher the fold, the more random noise we attenuate. Conventional 3D surveys are acquired using “swath”or “racetrack” vessel shooting, wherein the survey has a single line orientation (or “survey azimuth”), and a long, narrow spread of streamers are towed by a single vessel. Apart from the front of the streamers (short source-receiver offsets), most source-receiver combinations have a relatively common azimuth (the angle between their particular vector and the survey orientation, Figure 1). Thus, the subsurface geology is illuminated only from one particular shooting direction. We assume that most coherent noise types are well behaved and we can remove them in processing. We assume that the target illumination is acceptably uniform, and we can produce clean seismic images. Most of the time these assumptions are in the ballpark of truth and our resultant seismic data allow us to achieve our exploration and appraisal objectives.
Frequency content versus area coverage of 3D seismic, a key consideration for exploration and development of a shallow stratigraphic heavy oil trend in Neuquen Basin, Argentina
Authors: Cevallos Martin , Vaamonde Diego , Fortunato Gustavo
Published: May 2010

Exploring for shallow targets onshore normally involves low drilling cost but higher seismic cost to illuminate objectives with desired resolution. However, in underexplored acreage, the area covered by 3D seismic becomes an issue and should be balanced against the resolution needed to identify drillable prospects. If the play concepts are not well understood, exploration expenditures should be focused on wide 3D seismic acquisition and on cheap exploration drilling. If an economic discovery occurs, more sophisticated seismic acquisition could focus on the discovered reservoir. A “focused on target” acquisition might increase cost and limit the area extent.
Risking seismic amplitude anomaly prospects based on database trends
Authors: Forrest Mike , Roden Rocky , Holeywell Roger
Published: May 2010

Many oil companies routinely evaluate prospects for their drilling portfolio and seismic amplitude anomalies play an important role in this process. When these anomalies occur at a potential reservoir level, they are often called DHIs or direct hydrocarbon indicators, which are changes in reflection response that may be related to oil and/or gas accumulations. Examples of DHIs include bright spots, flat spots, dim spots, character/phase change at a projected oil or gas/water contact, and an amplitude variation with offset. Many uncertainties should be considered and analyzed in the process of assigning a probability of success and resource estimate range before including a seismic amplitude anomaly prospect in an oil company's prospect portfolio.
Uncertainties in the quantitative interpretation of lithology probability volumes
Authors: Sams M. S. , Saussus D.
Published: May 2010

The interpretation of deterministic seismic inversion results can be greatly enhanced through the generation of lithology probability cubes (e.g., Avseth et al., 2005). This is particularly true when there are more than two lithology types or when the inversion has produced estimates of P-impedance and S-impedance (or some combination of these). One method to generate the lithology probabilities is to derive probability density functions (PDFs) that relate the inverted elastic properties of the rocks to the probability of each lithology type (e.g., Sams and Saussus, 2010). These are applied to the elastic property volumes, within a Bayesian framework, to produce volumes of lithology probability. Ideally the process captures all of the uncertainties in the data, as well as those resulting from the inversion workflow and due to limited seismic resolution. The resultant lithology probability volumes can be visualized and manipulated for improved qualitative interpretation. For example, the sand probability cube in Figure 1a has been derived from the P-and S-impedance volumes shown in Figure 1a and 1b. The probability volume is intuitively easier to understand and therefore interpret than the elastic property volumes, particularly for those who have little insight into the elastic properties of rocks. Thresholds on probability and 3D connectivity criteria can be imposed to provide potential shapes of geological bodies.