bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inositol 1,4,5-trisphosphate-induced Ca2+ signalling is involved in estradiol-induced breast cancer epithelial cell growth
Authors: Szatkowski Cécilia , Parys Jan B , Ouadid-Ahidouch Halima , Matifat Fabrice 
Published: July 2010

AbstractBackgroundCa2+is a ubiquitous messenger that has been shown to be responsible for controlling numerous cellular processes including cell growth and cell death. Whereas the involvement of IP3-induced Ca2+signalling (IICS) in the physiological activity of numerous cell types is well documented, the role of IICS in cancer cells is still largely unknown. Our purpose was to characterize the role of IICS in the control of growth of the estrogen-dependent human breast cancer epithelial cell line MCF-7 and its potential regulation by 17β-estradiol (E2).ResultsOur results show that the IP3receptor (IP3R) inhibitors caffeine, 2-APB and xestospongin C (XeC) inhibited the growth of MCF-7 stimulated by 5% foetal calf serum or 10 nM E2. Furthermore, Ca2+imaging experiments showed that serum and E2were able to trigger, in a Ca2+-free medium, an elevation of internal Ca2+in a 2-APB and XeC-sensitive manner. Moreover, the phospholipase C (PLC) inhibitor U-73122 was able to prevent intracellular Ca2+elevation in response to serum, whereas the inactive analogue U-73343 was ineffective. Western-blotting experiments revealed that the 3 types of IP3Rs are expressed in MCF-7 cells and that a 48 hours treatment with 10 nM E2elevated IP3R3 protein expression level in an ICI-182,780 (a specific estrogen receptor antagonist)-dependent manner. Furthermore, IP3R3 silencing by the use of specific small interfering RNA was responsible for a drastic modification of the temporal feature of IICS, independently of a modification of the sensitivity of the Ca2+release process and acted to counteract the proliferative effect of 10 nM E2.ConclusionsAltogether, our results are in favour of a role of IICS in MCF-7 cell growth, and we hypothesize that the regulation of IP3R3 expression by E2is involved in this effect.
Challenges in measuring measles case fatality ratios in settings without vital registration
Authors: Cairns K Lisa , Nandy Robin , Grais Rebecca F 
Published: July 2010

AbstractMeasles, a highly infectious vaccine-preventable viral disease, is potentially fatal. Historically, measles case-fatality ratios (CFRs) have been reported to vary from 0.1% in the developed world to as high as 30% in emergency settings. Estimates of the global burden of mortality from measles, critical to prioritizing measles vaccination among other health interventions, are highly sensitive to the CFR estimates used in modeling; however, due to the lack of reliable, up-to-date data, considerable debate exists as to what CFR estimates are appropriate to use. To determine current measles CFRs in high-burden settings without vital registration we have conducted six retrospective measles mortality studies in such settings. This paper examines the methodological challenges of this work and our solutions to these challenges, including the integration of lessons from retrospective all-cause mortality studies into CFR studies, approaches to laboratory confirmation of outbreaks, and means of obtaining a representative sample of case-patients. Our experiences are relevant to those conducting retrospective CFR studies for measles or other diseases, and to those interested in all-cause mortality studies.
Slit and Netrin-1 guide cranial motor axon pathfinding via Rho-kinase, myosin light chain kinase and myosin II
Authors: Murray Ailish , Naeem Arifa , Barnes Sarah H , Drescher Uwe , Guthrie Sarah 
Published: July 2010

Abstract
Background
In the developing hindbrain, cranial motor axon guidance depends on diffusible repellent factors produced by the floor plate. Our previous studies have suggested that candidate molecules for mediating this effect are Slits, Netrin-1 and Semaphorin3A (Sema3A). It is unknown to what extent these factors contribute to floor plate-derived chemorepulsion of motor axons, and the downstream signalling pathways are largely unclear.

Results
In this study, we have used a combination of in vitro and in vivo approaches to identify the components of floor plate chemorepulsion and their downstream signalling pathways. Using in vitro motor axon deflection assays, we demonstrate that Slits and Netrin-1, but not Sema3A, contribute to floor plate repulsion. We also find that the axon pathways of dorsally projecting branchiomotor neurons are disrupted in Netrin-1 mutant mice and in chick embryos expressing dominant-negative Unc5a receptors, indicating an in vivo role for Netrin-1. We further demonstrate that Slit and Netrin-1 signalling are mediated by Rho-kinase (ROCK) and myosin light chain kinase (MLCK), which regulate myosin II activity, controlling actin retrograde flow in the growth cone. We show that MLCK, ROCK and myosin II are required for Slit and Netrin-1-mediated growth cone collapse of cranial motor axons. Inhibition of these molecules in explant cultures, or genetic manipulation of RhoA or myosin II function in vivo causes characteristic cranial motor axon pathfinding errors, including the inability to exit the midline, and loss of turning towards exit points.

Conclusions
Our findings suggest that both Slits and Netrin-1 contribute to floor plate-derived chemorepulsion of cranial motor axons. They further indicate that RhoA/ROCK, MLCK and myosin II are components of Slit and Netrin-1 signalling pathways, and suggest that these pathways are of key importance in cranial motor axon navigation.
Ependymal alterations in sudden intrauterine unexplained death and sudden infant death syndrome: possible primary consequence of prenatal exposure to cigarette smoking
Authors: Lavezzi Anna M , Corna Melissa F , Matturri Luigi 
Published: July 2010

Abstract
Background
The ependyma, the lining providing a protective barrier and filtration system separating brain parenchyma from cerebrospinal fluid, is still inadequately understood in humans. In this study we aimed to define, by morphological and immunohistochemical methods, the sequence of developmental steps of the human ependyma in the brainstem (ventricular ependyma) and thoracic spinal cord (central canal ependyma) of a large sample of fetal and infant death victims, aged from 17 gestational weeks to 8 postnatal months. Additionally, we investigated a possible link between alterations of this structure, sudden unexplained fetal and infant death and maternal smoking.

Results
Our results demonstrate that in early fetal life the human ependyma shows a pseudostratified cytoarchitecture including many tanycytes and ciliated cells together with numerous apoptotic and reactive astrocytes in the subependymal layer. The ependyma is fully differentiated, with a monolayer of uniform cells, after 32 to 34 gestational weeks. We observed a wide spectrum of ependymal pathological changes in sudden death victims, such as desquamation, clusters of ependymal cells in the subventricular zone, radial glial cells, and the unusual presence of neurons within and over the ependymal lining. These alterations were significantly related to maternal smoking in pregnancy.

Conclusions
We conclude that in smoking mothers, nicotine and its derivatives easily reach the cerebrospinal fluid in the fetus, immediately causing ependymal damage. Consequently, we suggest that the ependyma should be examined in-depth first in victims of sudden fetal or infant death with mothers who smoke.
Squamous cell carcinoma of the nipple following radiation therapy for ductal carcinoma in situ: a case report
Authors: Loveland-Jones Catherine E , Wang Fengwei , Bankhead Robin R , Huang Yajue , Reilly Kathleen J 
Published: July 2010

Abstract

Introduction
Radiation-induced nonmelanoma skin cancer was first reported seven years after the discovery of X-rays, but has received relatively little consideration in the literature. Specifically, nonmelanoma skin cancer after conservative surgery and radiation for early stage breast cancer has not been well studied. We report the case of a woman who developed squamous cell carcinoma of the nipple nine years after conservative surgery and radiation for ductal carcinoma in situ of the ipsilateral breast. We also review the relevant literature available to date.

Case presentation
A 66-year-old African-American woman presented to the hospital with a non-healing ulcer of the right nipple. Her past medical history was significant for right breast ductal carcinoma in situ for which she had undergone lumpectomy and whole breast radiation therapy nine years previously. Mammography and magnetic resonance imaging studies were negative for recurrent breast cancer. However, the latter demonstrated abnormal enhancement in the nipple-areolar region. An incisional biopsy of the lesion demonstrated invasive squamous cell carcinoma. Subsequently, the patient underwent wide excision of the nipple-areolar complex. Sentinel lymph-node biopsy was offered but our patient declined. She was considered to have local disease and hence no further treatment was recommended.

Conclusion
This case represents the first reported occurrence of squamous cell carcinoma of the nipple to follow conservative surgery and radiation for ductal carcinoma in situ of the ipsilateral breast. It is likely that radiation overexposure resulted in a radiation burn and subsequent radiodermatitis, placing it at risk for squamous cell carcinoma. A diagnosis of squamous cell carcinoma should be considered in a patient with a nipple lesion following radiation therapy for breast cancer.
Alterations of matrix metalloproteinases in the healthy elderly with increased risk of prodromal Alzheimer's disease
Authors: Stomrud Erik , Björkqvist Maria , Janciauskiene Sabina , Minthon Lennart , Hansson Oskar 
Published: July 2010

Abstract
Introduction
Matrix metalloproteinases (MMP) are believed to be involved in the pathologic processes behind Alzheimer's disease (AD). In this study, we aimed to examine the cerebrospinal fluid (CSF) levels of MMPs and tissue inhibitors of metalloproteinase-1 (TIMP-1) in individuals with AD dementia and cognitively healthy elderly individuals, and to investigate their relationship with established CSF biomarkers for Alzheimer's disease.

Methods
CSF was collected from 38 individuals with AD dementia and 34 cognitively healthy elderly individuals. The CSF was analyzed for MMP-1, MMP-3, MMP-9, TIMP-1, β-amyloid1-42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau). MMP/TIMP-1 ratios were calculated. APOE genotype was determined for the participants.

Results
AD patients had higher MMP-9/TIMP-1 ratios and lower TIMP-1 levels compared to cognitively healthy individuals. In AD patients, the MMP-9/TIMP-1 ratio correlated with CSF T-tau, a marker of neurodegeneration. Interestingly, the cognitively healthy individuals with risk markers for future AD, i.e. AD-supportive CSF biomarker levels of T-tau, P-tau and Aβ42 or the presence of the APOE ε4 allele, had higher CSF MMP-3 and MMP-9 levels and higher CSF MMP-3/TIMP-1 ratios compared to the healthy individuals without risk markers. The CSF levels of MMP-3 and -9 in the control group also correlated with the CSF T-tau and P-tau levels.

Conclusions
This study indicates that MMP-3 and MMP-9 might be involved in early pathogenesis of AD and that MMPs could be associated with neuronal degeneration and formation of neurofibrillary tangles even prior to development of overt cognitive dysfunction.
Synovial effusion and synovial fluid biomarkers in psoriatic arthritis to assess intraarticular tumor necrosis factor-α blockade in the knee joint
Authors: Fiocco Ugo , Sfriso Paolo , Oliviero Francesca , Roux-Lombard Pascale , Scagliori Elena , Cozzi Luisella , Lunardi Francesca , Calabrese Fiorella , Vezzù Maristella , Dainese Serena , Molena Beatrice , Scanu Anna , Nardacchione Roberto , Rubaltelli Leopoldo , Dayer Jean Michel , Punzi Leonardo 
Published: July 2010

Abstract
Introduction
The purpose of this study was theevaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-α blockers in psoriatic arthritis (PsA).

Methods
Systemic and local disease activity indexes (disease activity score (DAS); the Ritchie articular index (mRAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); Thompson articular (THOMP) and joint articular (KJAI)-Index ) and ST samples were assessed at baseline, throughout treatment, and during the follow-up in 14 patients affected with PsA who underwent IA injections (0.5 ml to 12.5 mg) in the knee joint of etanercept (E) or placebo (P) once every two weeks for a 10-week period. Total SF white blood cell (WBC) counts (WBC/μl) and SF cytokine/chemokine (CK/CCK) levels were measured before IA-E at baseline, after IA-E, and as long as there were adequate amounts of SF for knee aspiration (post). Characterization of synovial mononuclear cell infiltration and synovial vessels was carried out in 8 out of 14 knees by staining serial sections of synovial tissue biopsies for CD45, CD3, CD68, CD31 and CD105.

Results
At baseline, CRP and/or ESR were significantly correlated with SF-CK (interleukin- (IL-)1β, IL-1Ra, IL-6, IL-8) and CCK (CCL3). Post-IA injections, there was a decrease in SE in the knees in which aspiration following IA-E injection was possible as well as a significant reduction in SF WBC/μl and in SF-CK (IL-1β, IL-1Ra, IL-6 and IL-22). Pre- and post-IA-E injections, there were significant correlations between ST markers and SF-CK (IL-1β with CD45; IL-1β and IL-6 with CD31) and between SF-CCK (CCL4 and CCL3 with CD3). At the end of the study, there was a significant reduction in disease activity indexes (CRP, DAS, RAI, THOMP, KJAI) as well as in the ST markers (CD45; CD3).

Conclusions
Synovial effusion regression is a reliable indicator of the response to IA TNF-α blockers in PsA patients as it is confirmed by the correlation between SF biomarkers to disease activity and synovial tissue inflammation.
Mast cell function is not altered by Coronin-1A deficiency
Authors: Arandjelovic Sanja , Wickramarachchi Dilki , Hemmers Saskia , Leming Sunamita S , Kono Dwight H , Mowen Kerri A 
Published: July 2010

Abstract
Coronin-1A regulates F-actin levels in mast cells but is not required for survival, migration, cytokine secretion, degranulation, or Ca2+-flux generation upon antigen stimulation.
Coronin-1A is a WD repeat protein family member, highly expressed in all hematopoietic lineages, and acts as a regulator of F-actin dynamics and Ca2+ signaling. In Coro1aLmb3 mice results in inactivation of the protein and leads to disease resistance in a model of lupus erythematosus. In Coro1a−/− and Coro1aLmb3 mice, peripheral T cells exhibit impairments in survival, migration, activation, and Ca2+ flux. In this study, we show that in vitro-differentiated mast cells from Coro1aLmb3 mice are viable, developed normally, and are fully functional in assays of degranulation, cytokine secretion, and chemotactic migration, despite increased F-actin levels. In Coro1aLmb3 mast cells, Ca2+ flux in response to physiological FcɛRI stimulation is unaffected. Finally, Coro1aLmb3 mice showed similar in vivo mast cell responses as the WT mice. Coronin-1B and Coronin-1C expression levels were not increased in Coro1aLmb3 mast cells but were higher in mast cells than in CD4 T cells or B cells in WT mice. We conclude that Coronin-1A activity is not required for mast cell function.
β-Adrenergic stimulation increases macrophage CD14 expression and E. coli phagocytosis through PKA signaling mechanisms
Authors: Muthu Kuzhali , He Li-K , Szilagyi Andrea , Strotmon Patrick , Gamelli Richard L , Shankar Ravi 
Published: July 2010

Abstract
Long-term stimulation with isoproterenol augments macrophage CD14 expression and increases E. coli phagocytosis by cAMP-dependent protein kinase signaling mechanism.
CD14 is a glycoprotein that binds bacterial LPS in MØ. It is an essential component of the phagocytic system and is increased in septic shock. Critical injury and sepsis result in elevated endogenous CA levels. CAs have a significant impact on MØ inflammatory functions. We tested the hypothesis that β-adrenergic stimulation regulates CD14 expression and bacterial phagocytosis in BMØ. Murine BMØ stimulated with isoproterenol (&gt;8 h) induced a dose-dependent increase in cell surface CD14 expression. Specific PKA inhibitor (H-89) and gene-silencing (siRNA) studies demonstrated the role of cAMP-dependent PKA in mediating this response. In addition, we observed a correlation between an isoproterenol-mediated increase in CD14 expression and live Escherichia coli uptake in BMØ. Further, the essential role of CD14 in an isoproterenol-mediated increase in E. coli uptake was highlighted from experiments using CD14−/− mice. Moreover, the dose response of isoproterenol stimulation to CD14 expression and E. coli phagocytosis overlapped with similar EC50. Additionally, isoproterenol-mediated E. coli phagocytosis was prevented by H-89, suggesting that β-adrenergic stimulus in BMØ increases CD14 expression and live E. coli phagocytosis through a common signaling pathway. Our studies indicate the potential impact of β-adrenergic agents on important innate immune functions.
LAB/NTAL/Lat2: a force to be reckoned with in all leukocytes?
Authors: Orr Selinda J , McVicar Daniel W 
Published: July 2010

ABSTRACTLAB/NTAL/Lat2 is a transmembrane adaptor protein closely related to LAT. It is expressed in various myeloid and lymphoid cells, many of which also express LAT. Phosphorylation of LAB occurs following engagement of various ITAM- and non-ITAM-linked receptors and can play positive and negative roles following receptor engagement. LAT binds PLCγ directly, resulting in efficient Ca2+ flux and degranulation. However, LAB does not contain a PLCγ-binding motif and only binds PLCγ indirectly, possibly via Grb2, thereby resulting in suboptimal signaling. As LAT can signal more efficiently than LAB, competition between the 2 for space/substrates in the lipid rafts can attenuate signaling. This competition model requires coexpression of LAT; however, LAB is repressive, even in cells lacking substantial LAT expression such as macrophages and mature B cells. The reported interaction between LAB and the ubiquitin E3-ligase c-Cbl suggests 1 possible mechanism for LAT-independent inhibition by LAB, but such a model requires further investigation. Given the wide-reaching expression pattern of LAB, LAB has the ability to modulate signaling in virtually every type of leukocyte. Regardless of its ultimate mode of action, the potent regulatory capability of LAB proves this protein to be a complex adaptor that warrants continued, substantial scrutiny by biochemists and immunologists alike.
Next-Generation Sequencing Technology Reveals a Characteristic Pattern of Molecular Mutations in 72.8% of Chronic Myelomonocytic Leukemia by Detecting Frequent Alterations in TET2, CBL, RAS, and RUNX1
Authors: Kohlmann Alexander , Grossmann Vera , Klein Hans-Ulrich , Schindela Sonja , Weiss Tamara , Kazak Beray , Dicker Frank , Schnittger Susanne , Dugas Martin , Kern Wolfgang , Haferlach Claudia , Haferlach Torsten 
Published: July 2010

Purpose Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy that is characterized by features of both a myeloproliferative neoplasm and a myelodysplastic syndrome. Thus far, data on a comprehensive cytogenetic or molecular genetic characterization are limited. Patients and Methods Here, we analyzed 81 thoroughly characterized patients with CMML (CMML type 1, n = 45; CMML type 2, n = 36) by applying next-generation sequencing (NGS) technology to investigate CBL, JAK2, MPL, NRAS, and KRAS at known mutational hotspot regions. In addition, complete coding regions were analyzed for RUNX1 (β isoform) and TET2 aberrations. Results Cytogenetic aberrations were found in 18.2% of patients (14 of 77 patients). In contrast, at least one molecular mutation was observed in 72.8% of patients (59 of 81 patients). A mean of 1.6 mutations per patient was observed by this unprecedented screening. In total, 105 variances were detected by this comprehensive molecular screening. After excluding known polymorphisms or silent mutations, 82 distinct mutations remained (CBL, n = 15; JAK2V617F, n = 8; MPL, n = 0; NRAS, n = 10; KRAS, n = 12; RUNX1, n = 7; and TET2, n = 41). With respect to clinical data, a better outcome was seen for patients carrying TET2 mutations (P = .013). Conclusion The number of molecular markers used to categorize myeloid neoplasms is constantly increasing. Here, NGS screening has been demonstrated to support a comprehensive characterization of the molecular background in CMML. A pattern of molecular mutations translates into different biologic and prognostic categories of CMML.
Single-Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia: Long-Term Follow-Up Data
Authors: Mathews Vikram , George Biju , Chendamarai Ezhilarasi , Lakshmi Kavitha M. , Desire Salamun , Balasubramanian Poonkuzhali , Viswabandya Auro , Thirugnanam Rajashekar , Abraham Aby , Shaji Ramachandran Velayudhan , Srivastava Alok , Chandy Mammen 
Published: July 2010

Purpose We previously reported our results with a single-agent arsenic trioxide (ATO) –based regimen in newly diagnosed cases of acute promyelocytic leukemia (APL). The concern remained about the long-term outcome of this well-tolerated regimen. We report our long-term follow-up data on the same cohort. Patients and Methods From January 1998 to December 2004, 72 patients with PML/RARα+ APL were enrolled. All patients were treated with a single-agent ATO regimen. Results Overall 62 (86.1%) achieved a hematologic remission (complete remission). After the initial report, an additional seven patients have relapsed for a total of 13 relapses. There were no additional toxicities to report on follow-up. At a median follow-up 60 months, the 5-year Kaplan-Meier estimate (± SE) of event-free survival, disease-free survival, and overall survival (OS) was 69% ± 5.5%, 80% ± 5.2%, and 74.2% ± 5.2%, respectively. The OS in the good risk group as defined by us remains 100% over this period. Conclusion Single-agent ATO as used in this study in the management of newly diagnosed cases of APL is safe and is associated with durable responses. Results in the low-risk group are comparable to that reported with conventional therapy while additional interventions would probably be required in high-risk cases.