Neoplastic causes of abnormal puberty.

PubMed

Wendt, Susanne; Shelso, John; Wright, Karen; Furman, Wayne

2014-04-01

Neoplasm-related precocious puberty (PP) is a rare presenting feature of childhood cancer. Moreover, evaluation of suspected PP in a child is complex, and cancer is often not considered. We characterized the clinicopathologic features of patients presenting with PP at a large pediatric cancer center, reviewed the relevant literature, and developed an algorithm for the diagnostic work-up of these patients. We examined the records of all patients with a neoplasm and concomitant PP treated at St. Jude Children's Research Hospital from January 1975 through October 2011, reviewed the available literature, and analyzed the demographic, clinical, endocrine, and neoplasm-related features. Twenty-four of 13,615 children and adolescents (0.18%) were diagnosed with PP within 60 days of presentation. Primary diagnoses included brain tumor (12), adrenocortical carcinoma (5), hepatoblastoma (4), and others (3). PP was observed 0-48 months before diagnosis of neoplasm; 17 patients had peripheral PP and 7 had central PP. Neoplasm-related PP is rare and takes the form of a paraneoplastic syndrome caused by tumor production of hormones or by alteration of physiologic gonadotropin production. PP can precede diagnosis of malignancy by months or years, and neoplastic causes should be considered early to avoid delayed cancer diagnosis. Treatment of the primary malignancy resolved or diminished PP in surviving patients with an intact hypothalamic-pituitary-gonadal axis. © 2013 Wiley Periodicals, Inc.

Stromagenesis: the changing face of fibroblastic microenvironments during tumor progression.

PubMed

Beacham, Dorothy A; Cukierman, Edna

2005-10-01

During tumorigenesis, reciprocal changes in stromal fibroblasts and tumor cells induce changes to the neoplastic microenvironmental landscape. In stromagenesis, both the complex network of bi-directional stromal fibroblastic signaling pathways and the stromal extracellular matrix are modified. The presence of a 'primed' stroma during the early, reversible stage of tumorigenesis is optimal for stromal-directed therapeutic intervention. Three-dimensional (3D) cell culture systems have been developed that mimic the in vivo microenvironment. These systems provide unique experimental tools to identify early alterations in stromagenesis that are supportive of tumor progression with the ultimate goal of blocking neoplastic permissiveness and restoring normal phenotypes.

The efficacy of real-time colour Doppler flow imaging on endoscopic ultrasonography for differential diagnosis between neoplastic and non-neoplastic gallbladder polyps.

PubMed

Kim, Su Young; Cho, Jae Hee; Kim, Eui Joo; Chung, Dong Hae; Kim, Kun Kuk; Park, Yeon Ho; Kim, Yeon Suk

2018-05-01

We evaluated the usefulness of real-time colour Doppler flow (CDF) endoscopic ultrasonography (EUS) for differentiating neoplastic gallbladder (GB) polyps from non-neoplastic polyps. Between August 2014 and December 2016, a total of 233 patients with GB polyps who underwent real-time CDF-EUS were consecutively enrolled in this prospective study. CDF imaging was subjectively categorized for each patient as: strong CDF pattern, weak CDF pattern and no CDF pattern. Of the 233 patients, 115 underwent surgical resection. Of these, there were 90 cases of non-neoplastic GB polyps and 23 cases of neoplastic GB polyps. In a multivariate analysis, a strong CDF pattern was the most significant predictive factor for neoplastic polyps; sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 52.2 %, 79.4 %, 38.7 %, 86.9 % and 73.9 %, respectively. Solitary polyp and polyp size were associated with an increased risk of neoplasm. The presence of a strong CDF pattern as well as solitary and larger polyps on EUS may be predictive of neoplastic GB polyps. As real-time CDF-EUS poses no danger to the patient and requires no additional equipment, it is likely to become a supplemental tool for the differential diagnosis of GB polyps. • Differential diagnosis between neoplastic polyps and non-neoplastic polyps of GB is limited. • The use of real-time CDF-EUS was convenient, with high agreement between operators. • The real-time CDF-EUS is helpful in differential diagnosis of GB polyps.

Possible neoplastic effects of acrylamide on rat exocrine pancreas.

PubMed

Yener, Y; Kalipci, E; Öztaş, H; Aydin, A D; Yildiz, H

2013-01-01

We investigated whether the acrylamide formed during cooking carbohydrate-rich foods at high temperatures causes neoplastic changes in rat pancreas. Azaserine, which is an amino acid derivative that has the ability to initiate neoplastic changes in rat pancreas, was injected into 14-day-old male rats once a week for three weeks. Acrylamide was given to both azaserine-injected and non-injected rats at doses of 5 and 10 mg/kg/day in drinking water for 16 weeks after which tissue slides were prepared from the pancreata. Pancreas weights and body weights of rats treated with azaserine and acrylamide together increased significantly compared to the other groups. Moreover, the size, average diameter and volume of atypical acinar cell foci that developed in the pancreata of rats treated with azaserine and acrylamide together increased significantly compared to rats treated with either azaserine or acrylamide alone and control groups. Atypical acinar cell adenoma or adenocarcinoma was not observed in the pancreata of rats in any group.

Viral Oncolytic Therapeutics for Neoplastic Meningitis

DTIC Science & Technology

2013-07-01

SUBTITLE 5a. CONTRACT NUMBER Viral Oncolytic Therapeutics for Neoplastic Meningitis 5b. GRANT NUMBER W81XWH-11-1-0388 5c. PROGRAM ELEMENT NUMBER... viral and cellular kinetics with bioluminescence and PET are being written up for publication. 15. SUBJECT TERMS Neoplastic meningitis , mouse...model of meningeal metastases, breast cancer, bioluminescence, MRI, viral oncolysis, HSV- 1. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

Proposed Terminology and Classification of Pre-Malignant Neoplastic Conditions: A Consensus Proposal.

PubMed

Valent, Peter; Akin, Cem; Arock, Michel; Bock, Christoph; George, Tracy I; Galli, Stephen J; Gotlib, Jason; Haferlach, Torsten; Hoermann, Gregor; Hermine, Olivier; Jäger, Ulrich; Kenner, Lukas; Kreipe, Hans; Majeti, Ravindra; Metcalfe, Dean D; Orfao, Alberto; Reiter, Andreas; Sperr, Wolfgang R; Staber, Philipp B; Sotlar, Karl; Schiffer, Charles; Superti-Furga, Giulio; Horny, Hans-Peter

2017-12-01

Cancer evolution is a step-wise non-linear process that may start early in life or later in adulthood, and includes pre-malignant (indolent) and malignant phases. Early somatic changes may not be detectable or are found by chance in apparently healthy individuals. The same lesions may be detected in pre-malignant clonal conditions. In some patients, these lesions may never become relevant clinically whereas in others, they act together with additional pro-oncogenic hits and thereby contribute to the formation of an overt malignancy. Although some pre-malignant stages of a malignancy have been characterized, no global system to define and to classify these conditions is available. To discuss open issues related to pre-malignant phases of neoplastic disorders, a working conference was organized in Vienna in August 2015. The outcomes of this conference are summarized herein and include a basic proposal for a nomenclature and classification of pre-malignant conditions. This proposal should assist in the communication among patients, physicians and scientists, which is critical as genome-sequencing will soon be offered widely for early cancer-detection. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The EGFR family members sustain the neoplastic phenotype of ALK+ lung adenocarcinoma via EGR1

PubMed Central

Voena, C; Di Giacomo, F; Panizza, E; D'Amico, L; Boccalatte, F E; Pellegrino, E; Todaro, M; Recupero, D; Tabbò, F; Ambrogio, C; Martinengo, C; Bonello, L; Pulito, R; Hamm, J; Chiarle, R; Cheng, M; Ruggeri, B; Medico, E; Inghirami, G

2013-01-01

In non-small cell lung cancer (NSCLC), receptor tyrosine kinases (RTKs) stand out among causal dominant oncogenes, and the ablation of RTK signaling has emerged as a novel tailored therapeutic strategy. Nonetheless, long-term RTK inhibition leads invariably to acquired resistance, tumor recurrence and metastatic dissemination. In ALK+ cell lines, inhibition of ALK signaling was associated with coactivation of several RTKs, whose pharmacological suppression reverted the partial resistance to ALK blockade. Remarkably, ERBB2 signaling synergized with ALK and contributed to the neoplastic phenotype. Moreover, the engagement of wild-type epidermal growth factor receptor or MET receptors could sustain cell viability through early growth response 1 (EGR1) and/or Erk1/2; Akt activation and EGR1 overexpression prevented cell death induced by combined ALK/RTK inhibition. Membrane expression of ERBB2 in a subset of primary naive ALK+ NSCLC could be relevant in the clinical arena. Our data demonstrate that the neoplastic phenotype of ALK-driven NSCLC relays ‘ab initio' on the concomitant activation of multiple RTK signals via autocrine/paracrine regulatory loops. These findings suggest that molecular and functional signatures are required in de novo lung cancer patients for the design of efficacious and multi-targeted ‘patient-specific' therapies. PMID:23567620

The Spinal Instability Neoplastic Score: Impact on Oncologic Decision-Making.

PubMed

Versteeg, Anne L; Verlaan, Jorrit-Jan; Sahgal, Arjun; Mendel, Ehud; Quraishi, Nasir A; Fourney, Daryl R; Fisher, Charles G

2016-10-15

Systematic literature review. To address the following questions in a systematic literature review: 1. How is spinal neoplastic instability defined or classified in the literature before and after the introduction of the Spinal Instability Neoplastic Score (SINS)? 2. How has SINS affected daily clinical practice? 3. Can SINS be used as a prognostic tool? Spinal neoplastic-related instability was defined in 2010 and simultaneously SINS was introduced as a novel tool with criteria agreed upon by expert consensus to assess the degree of spinal stability. PubMed, Embase, and clinical trial databases were searched with the key words "spinal neoplasm," "spinal instability," "spinal instability neoplastic score," and synonyms. Studies describing spinal neoplastic-related instability were eligible for inclusion. Primary outcomes included studies describing and/or defining neoplastic-related instability, SINS, and studies using SINS as a prognostic factor. The search identified 1414 articles, of which 51 met the inclusion criteria. No precise definition or validated assessment tool was used specific to spinal neoplastic-related instability prior to the introduction of SINS. Since the publication of SINS in 2010, the vast majority of the literature regarding spinal instability has used SINS to assess or describe instability. Twelve studies specifically investigated the prognostic value of SINS in patients who underwent radiotherapy or surgery. No consensus could be determined regarding the definition, assessment, or reporting of neoplastic-related instability before introduction of SINS. Defining spinal neoplastic-related instability and the introduction of SINS have led to improved uniform reporting within the spinal neoplastic literature. Currently, the prognostic value of SINS is controversial. N/A.

Neoplastic Bone Marrow Niche: Hematopoietic and Mesenchymal Stem Cells

PubMed Central

Saki, Najmaldin; Abroun, Saeid; Farshdousti Hagh, Majid; Asgharei, Farahnaz

2011-01-01

The neoplastic niche comprises complex interactions between multiple cell types and molecules requiring cell-cell signaling as well as local secretion. These niches are important for both the maintenance of cancer stem cells and the induction of neoplastic cells survival and proliferation. Each niche contains a population of tumor stem cells supported by a closely associated vascular bed comprising mesenchyme-derived cells and extracellular matrix. Targeting cancer stem cells and neoplastic niche may provide new therapies to eradicate tumors. Much progress has been very recently made in the understanding of the cellular and molecular interactions in the microenvironment of neoplastic niches. This review article provides an overview of the neoplastic niches in the bone marrow. In addition to highlighting recent advances in the field, we will also discuss components of the niche and their signaling pathways. PMID:23508881

Predicting early positive change in multisystemic therapy with youth exhibiting antisocial behaviors.

PubMed

Tiernan, Kristine; Foster, Sharon L; Cunningham, Phillippe B; Brennan, Patricia; Whitmore, Elizabeth

2015-03-01

This study examined individual and family characteristics that predicted early positive change in the context of Multisystemic Therapy (MST). Families (n = 185; 65% male; average youth age 15 years) receiving MST in community settings completed assessments at the outset of treatment and 6-12 weeks into treatment. Early positive changes in youth antisocial behavior were assessed using the caregiver report on the Child Behavior Checklist Externalizing Behaviors subscale and youth report on the Self-Report Delinquency Scale. Overall, families showed significant positive changes by 6-12 weeks into treatment; these early changes were maintained into midtreatment 6-12 weeks later. Families who exhibited clinically significant gains early in treatment were more likely to terminate treatment successfully compared with those who did not show these gains. Low youth internalizing behaviors and absence of youth drug use predicted early positive changes in MST. High levels of parental monitoring and low levels of affiliation with deviant peers (mechanisms known to be associated with MST success) were also associated with early positive change. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Incidence of infusion reactions to anti-neoplastic agents in early phase clinical trials: The MD Anderson Cancer Center experience.

PubMed

Bupathi, Manojkumar; Hajjar, Joud; Bean, Stacie; Fu, Siqing; Hong, David; Karp, Daniel; Stephen, Bettzy; Hess, Kenneth; Meric-Bernstam, Funda; Naing, Aung

2017-02-01

Infusion reactions (IRs) to anti-neoplastic agents require prompt recognition and immediate treatment to avert significant complications. We conducted a retrospective review of the medical records of consecutive patients who received anti-neoplastic therapy in the outpatient treatment center of the Department of Investigational Cancer Therapeutics from January 1, 2013 to November 30, 2013. Of the 597 patients who received treatment, 9 (1.5 %) had IRs (all ≤ grade 2). The most common IRs observed on first occurrence were chills (n = 5), itching, rash, and facial flushing (n = 3 each). There were no IR-related deaths. All the IRs were reversible with appropriate symptomatic treatment and the therapy was completed after temporary cessation of infusion in 7 of the 9 patients. The infusion was stopped in 2 patients due to symptoms suggestive of IgE-mediated allergic reaction and cytokine storm. Five of the 8 patients who were re-challenged with the same therapy developed a similar reaction. However, the infusion was completed in 4 of the 5 patients after administration of intravenous diphenhydramine and/or hydrocortisone, or slowing the rate of infusion. And, subsequent cycles with the same agents were uneventful. IRs to anti-neoplastic agents are rare. Though the clinical presentations are overlapping, most IRs are not IgE-mediated allergic reactions. Appropriate premedication and slow rate of infusion facilitates uneventful administration of the anti-neoplastic agents in subsequent cycles. Further study in a larger cohort of patients to identify biomarkers of hypersensitivity is warranted.

Local bone marrow renin-angiotensin system in primitive, definitive and neoplastic haematopoiesis.

PubMed

Haznedaroglu, Ibrahim C; Beyazit, Yavuz

2013-03-01

The locally active ligand peptides, mediators, receptors and signalling pathways of the haematopoietic BM (bone marrow) autocrine/paracrine RAS (renin-angiotensin system) affect the essential steps of definitive blood cell production. Haematopoiesis, erythropoiesis, myelopoiesis, formation of monocytic and lymphocytic lineages, thrombopoiesis and other stromal cellular elements are regulated by the local BM RAS. The local BM RAS is present and active even in primitive embryonic haematopoiesis. ACE (angiotensin-converting enzyme) is expressed on the surface of the first endothelial and haematopoietic cells, forming the marrow cavity in the embryo. ACE marks early haematopoietic precursor cells and long-term blood-forming CD34(+) BM cells. The local autocrine tissue BM RAS may also be active in neoplastic haematopoiesis. Critical RAS mediators such as renin, ACE, AngII (angiotensin II) and angiotensinogen have been identified in leukaemic blast cells. The local tissue RAS influences tumour growth and metastases in an autocrine and paracrine fashion via the modulation of numerous carcinogenic events, such as angiogenesis, apoptosis, cellular proliferation, immune responses, cell signalling and extracellular matrix formation. The aim of the present review is to outline the known functions of the local BM RAS within the context of primitive, definitive and neoplastic haematopoiesis. Targeting the actions of local RAS molecules could represent a valuable therapeutic option for the management of neoplastic disorders.

Platelet-derived growth factor (PDGF) in neoplastic and non-neoplastic cystic lesions of the central nervous system and in the cerebrospinal fluid.

PubMed Central

Nistér, M.; Enblad, P.; Bäckström, G.; Söderman, T.; Persson, L.; Heldin, C. H.; Westermark, B.

1994-01-01

The aim of this study was to determine the concentration of PDGF in vivo in neoplastic and non-neoplastic brain lesions. Fluid from cystic lesions and cerebrospinal fluid was tested in a radioreceptor assay that detects all described PDGF isoforms. High concentration of PDGF were found in cyst fluids from several astrocytomas, one metastatic melanoma, one metastatic lung adenocarcinoma and one intracerebral abscess. The PDGF concentrations were several times higher than the levels known to be required for maximal PDGF effects on cells in vitro. PDGF could also be detected in some non-neoplastic lesions, especially one intracerebral abscess. The finding of high amounts of PDGF in neoplastic lesions strongly supports the possibility that PDGF can be a mediator of tumour and stromal cell growth and motility in vivo. Comparison of PDGF and beta-thromboglobulin concentrations in the same fluids strongly indicates that the PDGF protein is locally produced rather than a result of platelet activation and derangement of the blood-brain barrier. PMID:8180030

DIAGNOSIS OF ENDOCRINE DISEASE: Differentiation of pathologic/neoplastic hypercortisolism (Cushing's syndrome) from physiologic/non-neoplastic hypercortisolism (formerly known as pseudo-Cushing's syndrome).

PubMed

Findling, James W; Raff, Hershel

2017-05-01

Endogenous hypercortisolism (Cushing's syndrome) usually implies the presence of a pathologic condition caused by either an ACTH-secreting neoplasm or autonomous cortisol secretion from a benign or malignant adrenal neoplasm. However, sustained or intermittent hypercortisolism may also accompany many medical disorders that stimulate physiologic/non-neoplastic activation of the HPA axis (formerly known as pseudo-Cushing's syndrome); these two entities may share indistinguishable clinical and biochemical features. A thorough history and physical examination is often the best (and sometimes only) way to exclude pathologic/neoplastic hypercortisolism. The presence of alcoholism, renal failure, poorly controlled diabetes and severe neuropsychiatric disorders should always raise suspicion that the presence of hypercortisolism may be related to physiologic/non-neoplastic Cushing's syndrome. As late-night salivary cortisol and low-dose dexamethasone suppression have good sensitivity and negative predictive value, normal studies exclude Cushing's syndrome of any form. However, these tests have imperfect specificity and additional testing over time with clinical follow-up is often needed. When there is persistent diagnostic uncertainty, secondary tests such as the DDAVP stimulation test and the dexamethasone-CRH test may provide evidence for the presence or absence of an ACTH-secreting tumor. This review will define and characterize the numerous causes of physiologic/non-neoplastic hypercortisolism and provide a rational clinical and biochemical approach to distinguish it from pathologic/neoplastic hypercortisolism (true Cushing's syndrome). © 2017 European Society of Endocrinology.

Sirtuin 1 stimulates the proliferation and the expression of glycolysis genes in pancreatic neoplastic lesions.

PubMed

Pinho, Andreia V; Mawson, Amanda; Gill, Anthony; Arshi, Mehreen; Warmerdam, Max; Giry-Laterriere, Marc; Eling, Nils; Lie, Triyana; Kuster, Evelyne; Camargo, Simone; Biankin, Andrew V; Wu, Jianmin; Rooman, Ilse

2016-11-15

Metabolic reprogramming is a feature of neoplasia and tumor growth. Sirtuin 1 (SIRT1) is a lysine deacetylase of multiple targets including metabolic regulators such as p53. SIRT1 regulates metaplasia in the pancreas. Nevertheless, it is unclear if SIRT1 affects the development of neoplastic lesions and whether metabolic gene expression is altered.To assess neoplastic lesion development, mice with a pancreas-specific loss of Sirt1 (Pdx1-Cre;Sirt1-lox) were bred into a KrasG12D mutant background (KC) that predisposes to the development of pancreatic intra-epithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC). Similar grade PanIN lesions developed in KC and KC;Sirt1-lox mice but specifically early mucinous PanINs occupied 40% less area in the KC;Sirt1-lox line, attributed to reduced proliferation. This was accompanied by reduced expression of proteins in the glycolysis pathway, such as GLUT1 and GAPDH.The stimulatory effect of SIRT1 on proliferation and glycolysis gene expression was confirmed in a human PDAC cell line. In resected PDAC samples, higher proliferation and expression of glycolysis genes correlated with poor patient survival. SIRT1 expression per se was not prognostic but low expression of Cell Cycle and Apoptosis Regulator 2 (CCAR2), a reported SIRT1 inhibitor, corresponded to poor patient survival.These findings open perspectives for novel targeted therapies in pancreatic cancer.

Hypothalamic beta-endorphin neurons suppress preneoplastic and neoplastic lesions development in 1,2-dimethylhydrazine induced rat colon cancer model.

PubMed

Murugan, Sengottuvelan; Dave, Yatee; Rakhit, Ankush; Sarkar, Dipak K

2017-01-01

In recent years, experimental studies demonstrated negative impacts of impaired body stress response on colonic pathologies. In this study, we tested if reducing body stress response by the use of β-endorphin (BEP) neuronal transplants in the hypothalamus suppresses pre-neoplastic and neoplastic lesions. Colon cancer was induced by injecting 1,2-dimethylhydrazine (DMH) for sixteen weeks in Sprague Dawley rats with BEP neuron transplants or control neuron transplants, and their colonic histopathologies, colon tissue levels of pro-inflammatory cytokines and epithelial-mesenchymal transition (EMT) proteins and splenic levels of cytotoxic proteins were measured. Our results revealed that DMH induced tumors in colon at 100% incidence in control rats but failed to induce colonic tumors in 70% of animal with BEP neuronal transplants. The mean volume of tumor at the colon was smaller in BEP neurons transplanted rats than those in controls. Histopathologies of colon tissues revealed that BEP neurons transplanted animals had lesser tissue lesions such as aberrant crypt foci (ACF) and adenocarcinoma development in the colon than those in control groups. Immunohistochemical and western blot analyses identified reduced expression of Ki-67, TNF-α and NF-κB nuclear translocation in colonic tissues of BEP neurons transplanted rats than those in controls. BEP neurons transplanted rats also showed reduced expressions of transcription factors linked to EMT like Snail, Twist, and N-cadherin, but increased the levels of an epithelial cell marker E-cadherin in colon tissue. Furthermore, splenic NK cells cytolytic proteins such as perforin, granzyme B and IFN-γ levels in BEP neurons transplanted rats were higher than those in control rats. These data suggest that BEP neuron transplants suppress the growth and progression of colonic tumors possibly by decreasing inflammatory mileu and EMT via activation of innate immune responses.

Vital-dye-enhanced multimodal imaging of neoplastic progression in a mouse model of oral carcinogenesis

NASA Astrophysics Data System (ADS)

Hellebust, Anne; Rosbach, Kelsey; Wu, Jessica Keren; Nguyen, Jennifer; Gillenwater, Ann; Vigneswaran, Nadarajah; Richards-Kortum, Rebecca

2013-12-01

In this longitudinal study, a mouse model of 4-nitroquinoline 1-oxide chemically induced tongue carcinogenesis was used to assess the ability of optical imaging with exogenous and endogenous contrast to detect neoplastic lesions in a heterogeneous mucosal surface. Widefield autofluorescence and fluorescence images of intact 2-NBDG-stained and proflavine-stained tissues were acquired at multiple time points in the carcinogenesis process. Confocal fluorescence images of transverse fresh tissue slices from the same specimens were acquired to investigate how changes in tissue microarchitecture affect widefield fluorescence images of intact tissue. Widefield images were analyzed to develop and evaluate an algorithm to delineate areas of dysplasia and cancer. A classification algorithm for the presence of neoplasia based on the mean fluorescence intensity of 2-NBDG staining and the standard deviation of the fluorescence intensity of proflavine staining was found to separate moderate dysplasia, severe dysplasia, and cancer from non-neoplastic regions of interest with 91% sensitivity and specificity. Results suggest this combination of noninvasive optical imaging modalities can be used in vivo to discriminate non-neoplastic from neoplastic tissue in this model with the potential to translate this technology to the clinic.

Omega-3 polyunsaturated fatty acids selectively inhibit growth in neoplastic oral keratinocytes by differentially activating ERK1/2

PubMed Central

Parkinson, Eric Kenneth

2013-01-01

The long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs)—eicosapentaenoic acid (EPA) and its metabolite docosahexaenoic acid (DHA)—inhibit cancer formation in vivo, but their mechanism of action is unclear. Extracellular signal-regulated kinase 1/2 (ERK1/2) activation and inhibition have both been associated with the induction of tumour cell apoptosis by n-3 PUFAs. We show here that low doses of EPA, in particular, inhibited the growth of premalignant and malignant keratinocytes more than the growth of normal counterparts by a combination of cell cycle arrest and apoptosis. The growth inhibition of the oral squamous cell carcinoma (SCC) lines, but not normal keratinocytes, by both n-3 PUFAs was associated with epidermal growth factor receptor (EGFR) autophosphorylation, a sustained phosphorylation of ERK1/2 and its downstream target p90RSK but not with phosphorylation of the PI3 kinase target Akt. Inhibition of EGFR with either the EGFR kinase inhibitor AG1478 or an EGFR-blocking antibody inhibited ERK1/2 phosphorylation, and the blocking antibody partially antagonized growth inhibition by EPA but not by DHA. DHA generated more reactive oxygen species and activated more c-jun N-terminal kinase than EPA, potentially explaining its increased toxicity to normal keratinocytes. Our results show that, in part, EPA specifically inhibits SCC growth and development by creating a sustained signalling imbalance to amplify the EGFR/ERK/p90RSK pathway in neoplastic keratinocytes to a supraoptimal level, supporting the chemopreventive potential of EPA, whose toxicity to normal cells might be reduced further by blocking its metabolism to DHA. Furthermore, ERK1/2 phosphorylation may have potential as a biomarker of n-3 PUFA function in vivo. PMID:23892603

Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus.

PubMed

Kastelein, Florine; Biermann, Katharina; Steyerberg, Ewout W; Verheij, Joanne; Kalisvaart, Marit; Looijenga, Leendert H J; Stoop, Hans A; Walter, Laurens; Kuipers, Ernst J; Spaander, Manon C W; Bruno, Marco J

2013-12-01

The value of surveillance for patients with Barrett's oesophagus (BO) is under discussion given the overall low incidence of neoplastic progression and lack of discriminative tests for risk stratification. Histological diagnosis of low-grade dysplasia (LGD) is the only accepted predictor for progression to date, but has a low predictive value. The aim of this study was therefore to evaluate the value of p53 immunohistochemistry for predicting neoplastic progression in patients with BO. We conducted a case-control study within a prospective cohort of 720 patients with BO. Patients who developed high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC) were classified as cases and patients without neoplastic progression were classified as controls. P53 protein expression was determined by immunohistochemistry in more than 12 000 biopsies from 635 patients and was scored independently by two expert pathologists who were blinded to long-term outcome. During follow-up, 49 (8%) patients developed HGD or OAC. P53 overexpression was associated with an increased risk of neoplastic progression in patients with BO after adjusting for age, gender, Barrett length and oesophagitis (adjusted relative risks (RR(a)) 5.6; 95% CI 3.1 to 10.3), but the risk was even higher with loss of p53 expression (RR(a) 14.0; 95% CI 5.3 to 37.2). The positive predictive value for neoplastic progression increased from 15% with histological diagnosis of LGD to 33% with LGD and concurrent aberrant p53 expression. Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with BO and appears to be a more powerful predictor of neoplastic progression than histological diagnosis of LGD.

Stokes shift spectroscopy for the early diagnosis of epithelial precancers in DMBA treated mouse skin carcinogenesis

NASA Astrophysics Data System (ADS)

Jeyasingh, Ebenezar; Singaravelu, Ganesan; Prakasarao, Aruna

2018-02-01

In this study, we aim to characterize the tissue transformation in dimethylbenz(a)anthracene (DMBA) treated mouse skin tumor model using stokes shift spectroscopy (SSS) technique for early detection of the neoplastic changes. Stokes shift (SS) spectra measured by scanning both excitation and emission wavelength simultaneously with a fixed wavelength of interval (Δλ=20 nm) in vivo from 33 DMBA treated animals and 6 control animals. The SS spectra of normal (n=6), hyperplasia (n=10), dysplasia (n=10), and WDSCC (n=13) of mice skin shows the distinct peaks around 300, 350, and 386 nm may be attributed to tryptophan, collagen, and NADH respectively. From the observed spectral differences and the ratio variables that resulted in better classification between groups, it is concluded that tryptophan, collagen, and NADH are the key fluorophores that undergo changes during tissue transformation process and hence they can be targeted as tumor markers for early neoplastic changes.

The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer

PubMed Central

Antonio, Nicole; Bønnelykke-Behrndtz, Marie Louise; Ward, Laura Chloe; Collin, John; Christensen, Ib Jarle; Steiniche, Torben; Schmidt, Henrik; Feng, Yi; Martin, Paul

2015-01-01

There is a long-standing association between wound healing and cancer, with cancer often described as a “wound that does not heal”. However, little is known about how wounding, such as following surgery, biopsy collection or ulceration, might impact on cancer progression. Here, we use a translucent zebrafish larval model of RasG12V-driven neoplasia to image the interactions between inflammatory cells drawn to a wound, and to adjacent pre-neoplastic cells. We show that neutrophils are rapidly diverted from a wound to pre-neoplastic cells and these interactions lead to increased proliferation of the pre-neoplastic cells. One of the wound-inflammation-induced trophic signals is prostaglandin E2 (PGE2). In an adult model of chronic wounding in zebrafish, we show that repeated wounding with subsequent inflammation leads to a greater incidence of local melanoma formation. Our zebrafish studies led us to investigate the innate immune cell associations in ulcerated melanomas in human patients. We find a strong correlation between neutrophil presence at sites of melanoma ulceration and cell proliferation at these sites, which is associated with poor prognostic outcome. PMID:26136213

34 CFR 303.12 - Early intervention service provider.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 2 2014-07-01 2013-07-01 true Early intervention service provider. 303.12 Section 303... EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS WITH DISABILITIES General Definitions Used in This Part § 303.12 Early intervention service...

34 CFR 303.12 - Early intervention service provider.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 2 2012-07-01 2012-07-01 false Early intervention service provider. 303.12 Section 303... EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS WITH DISABILITIES General Definitions Used in This Part § 303.12 Early intervention service...

34 CFR 303.12 - Early intervention service provider.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 2 2013-07-01 2013-07-01 false Early intervention service provider. 303.12 Section 303... EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS WITH DISABILITIES General Definitions Used in This Part § 303.12 Early intervention service...

Depleted uranium induces neoplastic transformation in human lung epithelial cells.

PubMed

Xie, Hong; LaCerte, Carolyne; Thompson, W Douglas; Wise, John Pierce

2010-02-15

Depleted uranium (DU) is commonly used in military armor and munitions, and thus, exposure of soldiers and noncombatants is frequent and widespread. Previous studies have shown that DU has both chemical and radiological toxicity and that the primary route of exposure of DU to humans is through inhalation and ingestion. However, there is limited research information on the potential carcinogenicity of DU in human bronchial cells. Accordingly, we determined the neoplastic transforming ability of particulate DU to human bronchial epithelial cells (BEP2D). We observed the loss of contact inhibition and anchorage independent growth in cells exposed to DU after 24 h. We also characterized these DU-induced transformed cell lines and found that 40% of the cell lines exhibit alterations in plating efficiency and no significant changes in the cytotoxic response to DU. Cytogenetic analyses showed that 53% of the DU-transformed cell lines possess a hypodiploid phenotype. These data indicate that human bronchial cells are transformed by DU and exhibit significant chromosome instability consistent with a neoplastic phenotype.

Predictive factors of neoplastic gallbladder polyps: Outcomes of 278 patients.

PubMed

Terzioğlu, Serdar Gökay; Kılıç, Murat Özgür; Sapmaz, Ali; Karaca, Ahmet Serdar

2017-05-01

Distinguishing between neoplastic and nonneoplastic gallbladder polyps (GBPs) in the preoperative workup is of great importance for appropriate treatment. The present study aimed to investigate the characteristics of GBPs and to determine potential predictive factors of neoplastic polyps. The data of 278 patients who were confirmed to have GBPs through laparoscopic cholecystectomy were retrospectively analyzed. Polyps were classified as nonneoplastic and neoplastic GBPs, according to histopathological diagnoses. All clinicopathological characteristics were compared between these two groups. There were 264 (95%) nonneoplastic GBPs and 14 (5%) neoplastic GBPs. In univariate analysis, there were significant differences in age with a cutoff value of 60 years (p=0.002), polyp size (p<0.001), number of polyps (p=0.014), and polyp morphology (p<0.001) between the groups. Multivariate analysis showed that solitary polyp (p<0.001) and sessile morphology (p<0.001) were the independent predictors of neoplastic GBPs. Receiver-operating characteristic curve analysis of three cut-off values of polyp sizes (6, 10, and 15 mm) indicated that a polyp size of 10 mm had the highest area under curve (0.942). Age above 60 years, solitary polyps larger than 1 cm, and sessile morphology are associated with an increased risk of neoplasia in GBP. Therefore, these characteristics should be considered in the management of GBPs to reduce the incidence of unnecessary surgeries and to prevent delays in the treatment of a possible cancer.

Genetic polymorphisms and protein expression of P53 and BRCA1 in preneoplastic and neoplastic rat mammary glands.

PubMed

Al-Dhaheri, Wafa; Hassouna, Imam; Karam, Sherif M

2018-05-01

Breast cancer is the most common type of cancer and the leading cause of cancer-related deaths among women in the United Arab Emirates and worldwide. Although many factors contribute to the high incidence of breast cancer, a considerable number of cases are related to environmental factors. In the present study, breast cancer was induced in female rats using a single dose, 80 mg/kg body wt, of the environmental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). The aim of the present study, was to characterize some of the molecular changes that occur during breast cancer development in the DMBA-treated rat model. Mammary gland tissues of control and DMBA-treated rats were processed for: i) immunohistochemical probing using anti-BRCA1 antibody to characterize and correlate the localization of this cell cycle protein during progression to cancer, ii) western blotting to analyze the alteration of p53 protein expression in preneoplastic and neoplastic lesions of the mammary glands, and iii) polymerase chain reactions using primers specific for BRCA1 and P53 genes followed by single stranded conformational polymorphism (SSCP) or restriction fragment length polymorphism (RFLP) assays to detect possible mutations in these genes during development of breast cancer. Microscopic examination revealed a wide range of preneoplastic and neoplastic lesions providing a sequence representing the multistep process of breast cancer formation in DMBA-treated rats. Probing for BRCA1 protein revealed a gradual defect in its translocation from the cytoplasm to the nucleus during breast cancer progression. In control rats, BRCA1 was present in the nuclei of terminal duct epithelial cells. However, in the preneoplastic lesions, BRCA1 was localized in both the cytoplasm and nuclei of the epithelial duct cells. In all malignant lesions, BRCA1 was mostly found in the cytoplasm. Western blotting revealed initial downregulation in the expression of p53 protein during breast cancer

Collaborating with the enemy: function of macrophages in the development of neoplastic disease.

PubMed

Eljaszewicz, Andrzej; Wiese, Małgorzata; Helmin-Basa, Anna; Jankowski, Michal; Gackowska, Lidia; Kubiszewska, Izabela; Kaszewski, Wojciech; Michalkiewicz, Jacek; Zegarski, Wojciech

2013-01-01

Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc.), neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect), induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages dependent, since these cells show proangiogenic properties, attenuate the adaptive response (anergization of naïve T lymphocytes, induction of Treg cell formation, polarization of immune response towards Th2, etc.), and support invasion and metastases formation. Tumor-associated macrophages (TAMs), a predominant component of leukocytic infiltrate, "cooperate" with the neoplastic tissue, leading to the intensified proliferation and the immune escape of the latter. This paper characterizes the function of macrophages in the development of neoplastic disease.

Probiotics against neoplastic transformation of gastric mucosa: effects on cell proliferation and polyamine metabolism.

PubMed

Russo, Francesco; Linsalata, Michele; Orlando, Antonella

2014-10-07

Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori, little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines (putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism.

Discrimination between neoplastic and non-neoplastic lesions in cirrhotic liver using contrast-enhanced ultrasound

PubMed Central

Xu, H-X; Lu, M-D; Liu, L-N; Zhang, Y-F; Guo, L-H; Xu, J-M; Liu, C

2012-01-01

Objectives To assess the value of contrast-enhanced ultrasound (CEUS) in differentiating hepatocellular carcinoma (HCC) from non-neoplastic lesion in cirrhotic liver in comparison with baseline ultrasound. Methods A total of 147 nodules (diameter ≤5.0 cm) in 133 cirrhotic patients (mean age±standard deviation: 52±13 years, range 20–82 years; gender: 111 males and 22 females) were examined with CEUS. There were 116 HCCs, 26 macroregenerative nodules and 5 high-grade dysplastic nodules. CEUS was performed with a real-time contrast-specific mode and a sulphur hexafluoride-filled microbubble contrast agent. Results Hypervascularity was observed in 94.8% (110/116) HCCs, 3.8% (1/26) macroregenerative nodules and 60.0% (3/5) high-grade dysplastic nodules during arterial phase on CEUS. Detection rates of typical vascular pattern (i.e. hypervascularity during arterial phase and subsequent washout) in HCCs with a diameter of ≤2.0 cm, 2.1–3.0 cm and 3.1–5.0 cm were 69.2% (27/39), 97.1% (33/34) and 100.0% (43/43), respectively. CEUS significantly improved the sensitivity [88.8% (103/116) vs 37.1% (43/116), p<0.001], negative predictive value [70.5% (31/44) vs 31.5% (29/92), p<0.001], and accuracy [91.2% (134/147) vs 49.0% (72/147), p<0.001] in differentiating HCCs from non-neoplastic lesions when compared with baseline ultrasound. However, the sensitivity and accuracy of CEUS for HCCs ≤2.0 cm in diameter were significantly lower than those for HCCs of 2.1–3.0 cm and 3.1–5.0 cm in diameter. Conclusions CEUS improves diagnostic performance in differentiating HCCs from non-neoplastic nodules in cirrhotic patients compared with baseline ultrasound. Diagnosis of HCCs ≤2.0 cm diameter by CEUS is still a clinical concern, and thus needs further investigation. PMID:22553290

The potential influence of radiation-induced microenvironments in neoplastic progression

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

1998-01-01

Ionizing radiation is a complete carcinogen, able both to initiate and promote neoplastic progression and is a known carcinogen of human and murine mammary gland. Tissue response to radiation is a composite of genetic damage, cell death and induction of new gene expression patterns. Although DNA damage is believed to initiate carcinogenesis, the contribution of these other aspects of radiation response are beginning to be explored. Our studies demonstrate that radiation elicits rapid and persistent global alterations in the mammary gland microenvironment. We postulate that radiation-induced microenvironments may affect epithelial cells neoplastic transformation by altering their number or susceptibility. Alternatively, radiation induced microenvironments may exert a selective force on initiated cells and/or be conducive to progression. A key impetus for these studies is the possibility that blocking these events could be a strategy to interrupt neoplastic progression.

Continuity and Change in Poor Sleep from Childhood to Early Adolescence

PubMed Central

Pesonen, Anu-Katriina; Martikainen, Silja; Heinonen, Kati; Wehkalampi, Karoliina; Lahti, Jari; Kajantie, Eero; Räikkönen, Katri

2014-01-01

Study Objectives: We examined associations between pubertal maturation and sleep in early adolescence, at age 12 y, and continuity and change in actigraphy-based sleep and parent-reported sleep disorders from age 8 to 12 y. We also explored longitudinal associations between actigraph estimates of sleep and sleep disorders. Design: A cohort study of children born in 1998 and tested at ages 8 y (standard deviation [SD] = 0.3) and 12 y (SD = 0.5). Participants: A total of 348 children participated in cross-sectional analyses. We had longitudinal actigraphy data for 188 children and repeated parent reports of sleep disorders for 229 children. Measurements and Results: At age 8 y, participants wore actigraphs for 7.1 nights (SD = 1.2, range 3-14) on average and at age 12 y for 8.4 nights (SD = 1.7, range 3-11). Sleep disorders were parent-rated based on the Sleep Disturbance Scale for Children. Pubertal maturity was self-reported at age 12 y using the continuous Pubertal Development Scale and the picture-assisted categorical Tanner scales. Results: Significant mean-level changes toward shorter but higher quality sleep occurred over time. Sleep variables had low to high rank-order stability over time. Sleep disorders were highly stable from age 8 to 12 y. Actigraphy-based sleep and parent-rated sleep disorders showed no association either in cross-section or longitudinally. Pubertal maturation was not associated with worse sleep. Conclusions: Sleep in early adolescence can be anticipated from childhood sleep patterns and disorders, but is not associated with pubertal maturity. Although sleep duration becomes shorter, sleep quality may improve during early adolescence. Parent-rated sleep disorders are distinct from actigraph estimates of sleep. Citation: Pesonen AK; Martikainen S; Heinonen K; Wehkalampi K; Lahti J; Kajantie E; Räikkönen K. Continuity and change in poor sleep from childhood to early adolescence. SLEEP 2014;37(2):289-297. PMID:24497657

Diagnostic accuracy of transabdominal high-resolution US for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with EUS.

PubMed

Lee, Jeong Sub; Kim, Jung Hoon; Kim, Yong Jae; Ryu, Ji Kon; Kim, Yong-Tae; Lee, Jae Young; Han, Joon Koo

2017-07-01

To compare the diagnostic accuracy of transabdominal high-resolution ultrasound (HRUS) for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with endoscopic ultrasound (EUS) and pathology. Among 125 patients who underwent both HRUS and EUS, we included 29 pathologically proven cancers (T1 = 7, T2 = 19, T3 = 3) including 15 polypoid cancers and 50 surgically proven polyps (neoplastic = 30, non-neoplastic = 20). We reviewed formal reports and assessed the accuracy of HRUS and EUS for diagnosing cancer as well as the differential diagnosis of neoplastic polyps. Statistical analyses were performed using chi-square tests. The sensitivity, specificity, PPV, and NPV for gallbladder cancer were 82.7 %, 44.4 %, 82.7 %, and 44 % using HRUS and 86.2 %, 22.2 %, 78.1 %, and 33.3 % using EUS. HRUS and EUS correctly diagnosed the stage in 13 and 12 patients. The sensitivity, specificity, PPV, and NPV for neoplastic polyps were 80 %, 80 %, 86 %, and 73 % using HRUS and 73 %, 85 %, 88 %, and 69 % using EUS. Single polyps (8/20 vs. 21/30), larger (1.0 ± 0.28 cm vs. 1.9 ± 0.85 cm) polyps, and older age (52.5 ± 13.2 vs. 66.1 ± 10.3 years) were common in neoplastic polyps (p < 0.05). Transabdominal HRUS showed comparable accuracy for diagnosing gallbladder cancer and differentiating neoplastic polyps compared with EUS. HRUS is also easy to use during our routine ultrasound examinations. • HRUS showed comparable diagnostic accuracy for GB cancer compared with EUS. • HRUS and EUS showed similar diagnostic accuracy for differentiating neoplastic polyps. • Single, larger polyps and older age were common in neoplastic polyps. • HRUS is less invasive compared with EUS.

Probiotics against neoplastic transformation of gastric mucosa: Effects on cell proliferation and polyamine metabolism

PubMed Central

Russo, Francesco; Linsalata, Michele; Orlando, Antonella

2014-01-01

Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori, little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines (putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism. PMID:25309063

Changing Trends within the Population of Children Who Are Deaf or Hard of Hearing in Flanders (Belgium): Effects of 12 Years of Universal Newborn Hearing Screening, Early Intervention, and Early Cochlear Implantation

ERIC Educational Resources Information Center

De Raeve, Leo; Lichtert, Guido

2012-01-01

The purpose of this study is to show the changing trends within the population of children who are deaf and hard of hearing in Belgium over the last 12 years. The combination of Universal Newborn Hearing Screening programs, early intervention, and cochlear implants have tremendously influenced the education and support of children who are deaf or…

Simultaneous Dual Selective Targeted Delivery of Two Covalent Gemcitabine Immunochemotherapeutics and Complementary Anti-Neoplastic Potency of [Se]-Methylselenocysteine

PubMed Central

Coyne, C. P.; Jones, Toni; Bear, Ryan

2015-01-01

The anti-metabolite chemotherapeutic, gemcitabine is relatively effective for a spectrum of neoplastic conditions that include various forms of leukemia and adenocarcinoma/carcinoma. Rapid systemic deamination of gemcitabine accounts for a brief plasma half-life but its sustained administration is often curtailed by sequelae and chemotherapeutic-resistance. A molecular strategy that diminishes these limitations is the molecular design and synthetic production of covalent gemcitabine immunochemotherapeutics that possess properties of selective “targeted” delivery. The simultaneous dual selective “targeted” delivery of gemcitabine at two separate sites on the external surface membrane of a single cancer cell types represents a therapeutic approach that can increase cytosol chemotherapeutic deposition; prolong chemotherapeutic plasma half-life (reduces administration frequency); minimize innocent exposure of normal tissues and healthy organ systems; and ultimately enhance more rapid and thorough resolution of neoplastic cell populations. Materials and Methods: A light-reactive gemcitabine intermediate synthesized utilizing succinimidyl 4,4-azipentanoate was covalently bound to anti-EGFR or anti-HER2/neu IgG by exposure to UV light (354-nm) resulting in the synthesis of covalent immunochemotherapeutics, gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu]. Cytotoxic anti-neoplastic potency of gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] between gemcitabine-equivalent concentrations of 10−12 M and 10−6 M was determined utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKRr-3). The organoselenium compound, [Se]-methylselenocysteine was evaluated to determine if it complemented the anti-neoplastic potency of the covalent gemcitabine immunochemotherapeutics. Results: Gemcitabine-(C4-amide)-[anti-EGFR], gemcitabine-(C4-amide)-[anti-HER2/neu] and the dual simultaneous combination of gemcitabine

Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues.

PubMed

Morimoto, Ryo; Satoh, Fumitoshi; Murakami, Osamu; Hirose, Takuo; Totsune, Kazuhito; Imai, Yutaka; Arai, Yoichi; Suzuki, Takashi; Sasano, Hironobu; Ito, Sadayoshi; Takahashi, Kazuhiro

2008-07-01

Adrenomedullin 2/intermedin (AM2/IMD) is a new member of calcitonin/calcitonin gene-related peptide family. AM is expressed in various tumors including adrenocortical tumors and modulates tumor growth. The AM2/IMD expression has not been studied, however, in adrenal tumors. The expression of AM2/IMD and AM was therefore studied in human adrenal tumors and attached non-neoplastic adrenal tissues by immunocytochemistry (ICC). Immunoreactive (IR)-AM2/IMD was measured by RIA. Furthermore, the expression of AM2/IMD and its receptor components, calcitonin receptor-like receptor (CRLR), and receptor activity-modifying proteins (RAMPs) 1, 2, and 3 mRNA in these tissues was studied by reverse transcription PCR (RT-PCR). ICC showed that AM2/IMD and AM immunoreactivities were localized in adrenocortical tumors and pheochromocytomas. AM2/IMD and AM immunoreactivities were detected in medulla of attached non-neoplastic tissues, while the degree of immunoreactivity for AM2/IMD and AM in cortices of attached adrenals was relatively weak or undetectable. RIA detected IR-AM2/IMD in adrenal tumors (0.414+/-0.12 to 0.786+/-0.27 pmol/g wet weight, mean+/-S.E.M.) and attached adrenal tissues (0.397+/-0.052 pmol/g wet weight). Reverse-phase high-performance liquid chromatography showed one broad peak eluted in the similar position to synthetic AM2/IMD with several minor peaks. RT-PCR showed expression of AM2/IMD, CRLR, and RAMP1, RAMP2, and RAMP3 mRNA in tissues of adrenal tumors and attached adrenal glands. In conclusion, AM2/IMD is expressed in human adrenal tumors and attached non-neoplastic adrenal tissues and may play (patho-)physiological roles in normal and neoplastic adrenals as an autocrine/paracrine regulator.

Pre-operative factors that can predict neoplastic polypoid lesions of the gallbladder

PubMed Central

Cha, Byung Hyo; Hwang, Jin-Hyeok; Lee, Sang Hyub; Kim, Jang Eon; Cho, Jai Young; Kim, Haeryoung; Kim, So Yeon

2011-01-01

AIM: To investigate the preoperative factors that can predict neoplastic polypoid lesions of the gallbladder (PLGs) as well as malignant PLGs. METHODS: A retrospective analysis was conducted on the 210 consecutively enrolled patients who underwent cholecystectomy due to a PLG larger than 10 mm, as was determined by preoperative trans-abdominal ultrasonography or endoscopic ultrasonography. We analyzed the medical, laboratory, radiologic data and the pathologic results. RESULTS: In 210 cases, 146 had non-neoplastic polyps (69.5%) and 64 cases were neoplastic polyps (30.5%). An older age (≥ 65 years), the presence of diabetes mellitus (DM) and the size of polyp (≥ 15 mm) were revealed to be independent predictive variables for neoplastic polyps with odd ratios (OR) of 2.27 (P = 0.044), 2.64 (P = 0.021) and 4.94 (P < 0.01), respectively. Among the neoplastic PLGs, an older age (≥ 65 years), the presence of DM and polyp size (≥ 15 mm) were associated with malignancy with ORs of 4.97 (P = 0.005), 6.13 (P = 0.001) and 20.55 (P < 0.001), respectively. CONCLUSION: Among patients with PLGs larger than 10 mm in size, higher risk groups such as elderly patients more than 65 years old, those with DM or a large polyp size (≥ 15 mm) should be managed by cholecystectomy. PMID:21633532

Mesenchymal stromal cells of osteosarcoma patients do not show evidence of neoplastic changes during long-term culture.

PubMed

Buddingh, Emilie P; Ruslan, S Eriaty N; Reijnders, Christianne M A; Szuhai, Karoly; Kuijjer, Marieke L; Roelofs, Helene; Hogendoorn, Pancras C W; Maarten Egeler, R; Cleton-Jansen, Anne-Marie; Lankester, Arjan C

2015-01-01

In vitro expanded mesenchymal stromal cells (MSCs) are increasingly used as experimental cellular therapy. However, there have been concerns regarding the safety of their use, particularly with regard to possible oncogenic transformation. MSCs are the hypothesized precursor cells of high-grade osteosarcoma, a tumor with often complex karyotypes occurring mainly in adolescents and young adults. To determine if MSCs from osteosarcoma patients could be predisposed to malignant transformation we cultured MSCs of nine osteosarcoma patients and five healthy donors for an average of 649 days (range 601-679 days). Also, we compared MSCs derived from osteosarcoma patients at diagnosis and from healthy donors using genome wide gene expression profiling. Upon increasing passage, increasing frequencies of binucleate cells were detected, but no increase in proliferation suggestive of malignant transformation occurred in MSCs from either patients or donors. Hematopoietic cell specific Lyn substrate 1 (HLCS1) was differentially expressed (fold change 0.25, P value 0.0005) between MSCs of osteosarcoma patients (n = 14) and healthy donors (n = 9). This study shows that although HCLS1 expression was downregulated in MSCs of osteosarcoma patients and binucleate cells were present in both patient and donor derived MSCs, there was no evidence of neoplastic changes to occur during long-term culture.

Expression of Gab1 lacking the pleckstrin homology domain is associated with neoplastic progression.

PubMed

Kameda, H; Risinger, J I; Han, B B; Baek, S J; Barrett, J C; Abe, T; Takeuchi, T; Glasgow, W C; Eling, T E

2001-10-01

An in vitro transformation system of carcinogen-treated Syrian hamster embryo (SHE) cell cultures represents multistep genetic and nongenetic changes that develop during the neoplastic progression of normal cells to tumor cells in vivo. During this neoplastic progression, SHE cells demonstrate an altered response to epidermal growth factor (EGF). In the present report, we examined the role of the adapter protein Gab1 (Grb2-associated binder-1) in the neoplastic progression of SHE cells. We used two asbestos-transformed SHE cell clones in different neoplastic stages: a 10W+8 clone, which is immortal and retains the ability to suppress the tumorigenicity of tumor cells in cell-cell hybrid experiments, and a 10W-1 clone, which has lost this tumor suppressor ability. 10W+8 cells expressed full-length 100-kDa Gab1 and associated 5.2-kb mRNA. Upon repeated cell passaging, 10W-1 cells showed increasing expression of a novel 87-kDa form of Gab1 as well as 4.6-kb mRNA with diminishing expression of the original 100-kDa Gab1. cDNA encoding the 87-kDa Gab1 predicts a form of Gab1 lacking the amino-terminal 103 amino acids (Gab1(Delta1-103)), which corresponds to loss of most of the pleckstrin homology (PH) domain. Gab1(Delta1-103) retains the ability to be phosphorylated in an EGF-dependent manner and to associate with the EGF receptor and SHP-2 upon EGF stimulation. The endogenous expression of Gab1(Delta1-103) in 10W-1 cells appeared closely related to EGF-dependent colony formation in soft agar. Moreover, transfection and expression of Gab1(Delta1-103), but not Gab1, in 10W+8 cells enhanced their EGF-dependent colony formation in soft agar. These results demonstrate that Gab1 is a target of carcinogen-induced transformation of SHE cells and that the expression of a Gab1 variant lacking most of the PH domain plays a specific role in the neoplastic progression of SHE cells.

Selective binding of lectins to normal and neoplastic urothelium in rat and mouse bladder carcinogenesis models.

PubMed

Zupančič, Daša; Kreft, Mateja Erdani; Romih, Rok

2014-01-01

Bladder cancer adjuvant intravesical therapy could be optimized by more selective targeting of neoplastic tissue via specific binding of lectins to plasma membrane carbohydrates. Our aim was to establish rat and mouse models of bladder carcinogenesis to investigate in vivo and ex vivo binding of selected lectins to the luminal surface of normal and neoplastic urothelium. Male rats and mice were treated with 0.05 % N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water and used for ex vivo and in vivo lectin binding experiments. Urinary bladder samples were also used for paraffin embedding, scanning electron microscopy and immunofluorescence labelling of uroplakins. During carcinogenesis, the structure of the urinary bladder luminal surface changed from microridges to microvilli and ropy ridges and the expression of urothelial-specific glycoproteins uroplakins was decreased. Ex vivo and in vivo lectin binding experiments gave comparable results. Jacalin (lectin from Artocarpus integrifolia) exhibited the highest selectivity for neoplastic compared to normal urothelium of rats and mice. The binding of lectin from Amaranthus caudatus decreased in rat model and increased in mouse carcinogenesis model, indicating interspecies variations of plasma membrane glycosylation. Lectin from Datura stramonium showed higher affinity for neoplastic urothelium compared to the normal in rat and mouse model. The BBN-induced animal models of bladder carcinogenesis offer a promising approach for lectin binding experiments and further lectin-mediated targeted drug delivery research. Moreover, in vivo lectin binding experiments are comparable to ex vivo experiments, which should be considered when planning and optimizing future research.

12 CFR 1780.12 - Change of time limits.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Change of time limits. 1780.12 Section 1780.12 Banks and Banking OFFICE OF FEDERAL HOUSING ENTERPRISE OVERSIGHT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT RULES OF PRACTICE AND PROCEDURE RULES OF PRACTICE AND PROCEDURE General Rules § 1780.12 Change of...

Hypoechoic foci on EUS are simple and strong predictive factors for neoplastic gallbladder polyps.

PubMed

Cho, Jae Hee; Park, Jeong Youp; Kim, Yoon Jae; Kim, Hee Man; Kim, Hong Jeong; Hong, Sung Pil; Park, Seung Woo; Chung, Jae Bock; Song, Si Young; Bang, Seungmin

2009-06-01

EUS is an accurate imaging modality for delineating gallbladder (GB) structures; however, its clinical use in differentiating neoplastic GB polyps from nonneoplastic polyps is limited. Thus, we sought to characterize neoplastic GB polyps by analyzing unique EUS features. Our analysis revealed variably shaped, relatively hypoechoic portions in the core of polyps compared with general background echogenicity. Our purpose was to make a differential diagnosis between neoplastic and nonneoplastic GB polyps of less than 20 mm by use of EUS variables, including hypoechoic foci. Retrospective single-center study. University teaching hospital. Patients (n = 88) underwent preoperative EUS and cholecystectomy for GB polyps smaller than 20 mm. Hypoechoic foci were found in 30 of 33 patients (91%) with neoplastic polyps and 6 of 55 (11%) with nonneoplastic polyps. In a multivariate analysis, hypoechoic foci were the only significant predictive factor for neoplastic polyps (odds ratio [OR] 55.4, 95% CI, 8.26-371, P < .001); the sensitivity and specificity were 90% and 89%, respectively. In addition, polyps >15 mm had an increased risk of malignancy (OR 21.7, 95% CI, 2.35-201, P = .007), as did those with hypoechoic foci (OR 10.9; 95% CI, 1.01-117, P = .049). Retrospective review of selected patients from a tertiary medical center. The presence of hypoechoic foci on EUS is a strong predictive factor for neoplastic polyps. EUS may be useful in developing a treatment strategy for GB polyps.

Short- and long-term efficacy of focused ultrasound therapy for non-neoplastic epithelial disorders of the vulva.

PubMed

Wu, C; Zou, M; Xiong, Y; Wang, L; Chen, H; Fan, Y; Li, C

2017-08-01

To investigate the short- and long-term efficacy and influential factors of focused ultrasound for the treatment of non-neoplastic epithelial disorders of the vulva (NNEDV). A retrospective observational study. A gynaecologic department in a single centre in China. Patients with NNEDV were included in this study: 85 patients were diagnosed with lichen simplex chronicus (LSC), 44 patients with vulva lichen sclerosus (VLS), and seven patients with lichen planus (LP). A total of 136 eligible patients with NNEDV were treated with focused ultrasound. After the treatment, based on changes in the degree of symptom severity and local skin signs (lesion size, skin colour and elasticity) before and after treatment, the treatment effectiveness for each patient was assessed. We further analysed the relations among pathologic type, age, course and curative rate. Statistical analysis was performed using the Chi-square (McNemar) test. Improvement in the symptoms and physical signs and the predictive factors. Symptom relief was observed in all patients. The appearance and colour of the vulva returned to normal after the ultrasound treatment. Complete remission (CR) occurred in 68 of 136 (50%) patients (41 patients with LSC and 12 patients with VLS). The response rate was 93.38% (127/136). Seven patients who had a poor response to the first session of treatment were treated again with ultrasound therapy and a good response was observed. No severe complications were observed. There was no significant difference in treatment results among the different pathological types (P > 0.05). However, the course of the disease and the age of the patients were related to the treatment results (P < 0.05). NNEDV can be treated with focused ultrasound effectively and safely. The course of the disease and the age of the patients may be predictive factors. Patients with non-neoplastic epithelial disorders of the vulva can be safely and effectively treated with focused ultrasound. No significant

Lymphoproliferative lung disorders: a radiologic-pathologic overview. Part II: Neoplastic disorders.

PubMed

Restrepo, Carlos S; Carrillo, Jorge; Rosado de Christenson, Melissa; Ojeda Leon, Paulina; Lucia Rivera, Aura; Koss, Micheal N

2013-12-01

Lymphoproliferative pulmonary neoplasms can occur as primary pulmonary lymphomas or because of secondary pulmonary involvement. Neoplastic disorders may be difficult to differentiate from reactive pulmonary lymphoproliferative disorders, and immunohistochemical evaluation is often required to differentiate the 2 types of lesions. Neoplastic lymphoproliferative disorders are monoclonal lesions. Most affected patients present with systemic complaints, and imaging findings typically include nodules, masses, and lymphadenopathy. Primary pulmonary lymphomas are rare and account for less than 4% of the lymphomas that arise in extranodal sites. Secondary pulmonary lymphomas can affect the lung via hematogenous dissemination or by secondary involvement from tumor in adjacent or contiguous sites. Neoplastic lymphoproliferative lesions also include leukemia and plasma cell neoplasms. Posttransplantation lymphoproliferative disorders constitute a special type of lymphoid proliferation occurring in the setting of the chronic immunosuppression required for solid organ and bone marrow transplantation. Copyright © 2013 Elsevier Inc. All rights reserved.

2015 update on the diagnosis and management of neoplastic pericardial disease.

PubMed

Lestuzzi, Chiara; Berretta, Massimiliano; Tomkowski, Witold

2015-04-01

The best approach in diagnosis and treatment of neoplastic pericardial disease has not been defined yet. The authors report the most recent literature about the new diagnostic techniques that are useful to improve the diagnosis. The literature about the therapeutic options is critically reviewed, in order to give suggestions of use to the clinical practice. Pericardial effusion may require urgent drainage; the solid component, however, becomes predominant in some cases. Neoplastic pericardial disease should be assessed following oncologic criteria evaluation of the neoplastic burden; outcome classified as complete or partial response, stable or progressive disease and - in cases with progression - event-free survival. Systemic chemotherapy may be effective in lymphomas and possibly in breast carcinomas. Intrapericardial chemotherapy with systemic chemotherapy is the treatment of choice in lung cancer. Pericardial window with systemic chemotherapy is also effective in preventing the accumulation of large amount of fluid.

Skin signs of systemic infections and neoplastic diseases.

PubMed

Manuelyan, Karen L; Bogdanov, Ivan A; Darlenski, Razvigor B

2017-10-01

In recent years, emphasis on the physical examination has made way for a plethora of laboratory tests and sophisticated imaging diagnostic techniques. In addition, we are witnessing an underestimation of dermatology as a specialty around the world, which is accepted as an ambulatory specialty on the border of cosmetology and beautification. However, recognizing specific cutaneous clinical signs can facilitate timely diagnosis of various systemic infections and neoplastic diseases. Thus, a skilled dermatologist can play an essential role in the multidisciplinary team, involved in the care for systemically ill patients. In this article, we will focus on some life threatening systemic infections in which the skin changes can be a major clue for the diagnosis. Recent deadly epidemics will also be focused. Classic examples of paraneoplastic skin conditions will also be provided.

Spectroscopic analysis of normal and neoplastic (WI-FTC) thyroid tissue.

PubMed

Depciuch, Joanna; Stanek-Widera, Agata; Lange, Dariusz; Biskup-Frużyńska, Magdalena; Stanek-Tarkowska, Jadwiga; Czarny, Wojciech; Cebulski, Jozef

2018-06-07

Thyroid cancer holds the first place of the malignant tumors of the endocrine system. One of the less common thyroid cancers is follicular thyroid carcinoma (FTC), which is very difficult to diagnose because it gives the same image as adenoma, which is benign. Certainty of the diagnosis is gained only when FTC gives metastases. Therefore, it was decided to compare normal and neoplastic (FTC) thyroid tissues with Fourier Transform Infrared (FTIR) spectroscopy. The obtained FTIR spectra and Principal Component Analysis (PCA) allowed us to conclude that there are differences in the FTIR spectrum between normal tissues and those affected by cancer. In addition, the results indicate that there is a decrease in the number of functional groups that build cellular and tissue structures in tumoral tissues. The shifts of wave numbers corresponding to the protein and lipid function group vibrations, as well as the calculated second derivative of the FTIR spectra showed the structural changes in neoplastic tissues. Moreover, the deconvolution of the amide I massif indicates that in cancerous tissues the prevailing secondary structure is β-sheet structure, while in normal tissues it is α-helix. The obtained results allow us to conclude that infrared spectroscopy, in addition to providing information on the composition of tested samples, can be an excellent diagnostic tool contributing to understanding the FTC substrate. Copyright © 2018. Published by Elsevier B.V.

The flavonoid chrysin attenuates colorectal pathological remodeling reducing the number and severity of pre-neoplastic lesions in rats exposed to the carcinogen 1,2-dimethylhydrazine.

PubMed

Sequetto, Priscila L; Oliveira, Tânia T; Soares, Italo A C; Maldonado, Izabel R S C; Mello, Vanessa J; Pizziolo, Virginia R; Almeida, Márcia R; Novaes, Rômulo D

2013-05-01

Phenolic compounds are naturally occurring, bioactive substances with marked antioxidant and anti-inflammatory potential. The flavonoid chrysin, found in high levels in honey bee propolis, inhibits the activity of enzymes involved in carcinogenesis. We have investigated the effect of chrysin on pre-neoplastic colorectal lesions (ACF, aberrant crypt foci) in a rat model of chemical carcinogenesis induced by 1,2-dimethylhydrazine (DMH). Female Wistar rats weighing 137.2 ± 24.3 g received weekly one subcutaneous injection of DMH (20 mg/kg) for 10 weeks. The animals were divided into five groups each with seven animals: Group 1, 0.9% saline; Group 2, DMH+0.9% saline; Group 3, DMH+chrysin (10 mg/kg); Group 4, DMH+chrysin (100 mg/kg); Group 5, DMH+chrysin (200 mg/kg). Groups 2 and 3 showed a significant increase in ACF number, nucleolus organizer regions per enterocyte nucleus and nitrite/nitrate serum levels compared with Group 1. Groups 4 and 5 presented a significant reduction in all these parameters compared with Group 2. The levels of antioxidant minerals (copper, magnesium, selenium, zinc) and the number of enteroendocrine and mucin-producing cells were significantly reduced in Groups 2 and 3 but were similar in Groups 4 and 5 compared with Group 1. Chrysin, at 100 mg/kg and 200 mg/kg, was effective in attenuating pathological colorectal remodeling, reducing the number of pre-neoplastic lesions in rats exposed to DMH. Some of these effects might be attributable to the recovery of antioxidant mineral levels, a reduction in systemic nitrosative stress and an inhibition of the cellular proliferation induced by this flavonoid.

Prenatal Exposure to BPA Alters the Epigenome of the Rat Mammary Gland and Increases the Propensity to Neoplastic Development

PubMed Central

Dhimolea, Eugen; Wadia, Perinaaz R.; Murray, Tessa J.; Settles, Matthew L.; Treitman, Jo D.; Sonnenschein, Carlos; Shioda, Toshi; Soto, Ana M.

2014-01-01

Exposure to environmental estrogens (xenoestrogens) may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The xenoestrogen bisphenol A (BPA) leaches from plastic food/beverage containers and dental materials. Fetal exposure to BPA induces preneoplastic and neoplastic lesions in the adult rat mammary gland. Previous results suggest that BPA acts through the estrogen receptors which are detected exclusively in the mesenchyme during the exposure period by directly altering gene expression, leading to alterations of the reciprocal interactions between mesenchyme and epithelium. This initiates a long sequence of altered morphogenetic events leading to neoplastic transformation. Additionally, BPA induces epigenetic changes in some tissues. To explore this mechanism in the mammary gland, Wistar-Furth rats were exposed subcutaneously via osmotic pumps to vehicle or 250 µg BPA/kg BW/day, a dose that induced ductal carcinomas in situ. Females exposed from gestational day 9 to postnatal day (PND) 1 were sacrificed at PND4, PND21 and at first estrus after PND50. Genomic DNA (gDNA) was isolated from the mammary tissue and immuno-precipitated using anti-5-methylcytosine antibodies. Detection and quantification of gDNA methylation status using the Nimblegen ChIP array revealed 7412 differentially methylated gDNA segments (out of 58207 segments), with the majority of changes occurring at PND21. Transcriptomal analysis revealed that the majority of gene expression differences between BPA- and vehicle-treated animals were observed later (PND50). BPA exposure resulted in higher levels of pro-activation histone H3K4 trimethylation at the transcriptional initiation site of the alpha-lactalbumin gene at PND4, concomitantly enhancing mRNA expression of this gene. These results show that fetal BPA exposure triggers changes in the postnatal and adult mammary gland epigenome and alters gene expression patterns

Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry.

PubMed

Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

2015-01-01

To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student'st test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

43 CFR 12.70 - Changes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Changes. 12.70 Section 12.70 Public Lands... State and Local Governments Changes, Property, and Subawards § 12.70 Changes. (a) General. Grantees and... requirements and may make limited program changes to the approved project. However, unless waived by the...

Clinico-pathological studies on the effect of different anti-neoplastic chemotherapy regimens on transmissible venereal tumours in dogs.

PubMed

Singh, J; Rana, J S; Sood, N; Pangawkar, G R; Gupta, P P

1996-01-01

Thirty-two dogs affected with transmissible venereal tumour (TVT) were divided into three treatment groups. In group I vincristine sulphate at 0.025 mg/kg body weight, in group II vinblastine sulphate at 0.150 mg/kg body weight, and in group III vinblastine sulphate at 0.100 mg/kg body weight plus methotrexate at 0.35 mg/kg body weight were given intravenously at weekly intervals. Biopsies were performed on days 0, 3, 7 and 14. The tissues were preserved in 10% neutral buffered formalin and processed routinely for haematoxylin and eosin staining. Histopathologically, the untreated TVT was characterized by sheets or bundles of mostly rounded cells having a large, highly basophilic nucleus with a prominent, highly basophilic necleolus. Both vincristine and vinblastine primarily affected the nuclei of neoplastic cells, causing condensation, karyorrhexis and karyolysis within 3 days of chemotherapy. The regressing tumour mass showed marked infiltration by lymphocytes, lymphoblasts and macrophages by day 7. There was nearly complete regression of the tumour by day 14, as shown by the almost complete loss of neoplastic cells, with fibrous tissue substitution. However, in group III, the changes occurred more slowly and more injections were needed for complete regression. In both groups I and II, 11/12 of the animals responded completely to the chemotherapy within 3 weeks, while in group III, 6/8 of the dogs responded to the treatment by 21-28 days.

Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

PubMed Central

Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

2015-01-01

ABSTRACT Objective To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Methods Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’s t test. Results The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). Conclusion The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues. PMID:26761548

Anxious Depression and early changes in the HAMD-17 anxiety-somatization factor items and antidepressant treatment outcome

PubMed Central

Farabaugh, Amy H.; Bitran, Stella; Witte, Janet; Alpert, Jonathan; Chuzi, Sarah; Clain, Alisabet J.; Baer, Lee; Fava, Maurizio; McGrath, Patrick J.; Dording, Christina; Mischoulon, David; Papakostas, George I

2010-01-01

Objective To assess the relationship between early changes in anxiety/somatization symptoms and treatment outcome among MDD subjects during a 12-week trial of fluoxetine. We also examined the relationship between anxious depression and treatment response. Methods 510 MDD patients received 12 weeks of fluoxetine with flexible dosing (target dosages: 10 mg/day (week 1), 20 mg/day (weeks 2–4), 40 mg/day (weeks 4–8), and 60 mg/day (weeks 5–12)). We assessed the relationship between early changes in HAMD-17- anxiety/somatization factor items and depressive remission, as well as whether anxious depression at baseline predicted remission at study endpoint. . Baseline HAMD-17 scores were considered as covariates and the Bonferroni correction (p ≤ .008) was used for multiple comparisons. Results Adjusting for baseline HAMD-17 scores, patients who experienced greater early improvement in somatic symptoms (gastrointestinal) were significantly more likely to attain remission (HAMD-17 < 8) at endpoint than those without early improvement (p = .006). Early changes in the remaining items did not predict remission, nor did anxious depression at baseline. Conclusions Among the anxiety/somatization factor items, only early changes in somatic symptoms (gastrointestinal) predicted remission. Future studies are warranted to further investigate this relationship, as well as that between anxious depression and treatment outcome. PMID:20400905

Quantitative evaluation of RASSF1A methylation in the non-lesional, regenerative and neoplastic liver

PubMed Central

Di Gioia, Sonia; Bianchi, Paolo; Destro, Annarita; Grizzi, Fabio; Malesci, Alberto; Laghi, Luigi; Levrero, Massimo; Morabito, Alberto; Roncalli, Massimo

2006-01-01

Background Epigenetic changes during ageing and their relationship with cancer are under the focus of intense research. RASSF1A and NORE1A are novel genes acting in concert in the proapoptotic pathway of the RAS signalling. While NORE1A has not been previously investigated in the human liver, recent reports have suggested that RASSF1A is frequently epigenetically methylated not only in HCC but also in the cirrhotic liver. Methods To address whether epigenetic changes take place in connection to age and/or to the underlying disease, we investigated RASSF1A and NORE1A gene promoter methylation by conventional methylation specific PCR and Real-Time MSP in a series of hepatitic and non-hepatitic livers harboring regenerative/hyperplastic (cirrhosis/focal nodular hyperplasia), dysplastic (large regenerative, low and high grade dysplastic nodules) and neoplastic (hepatocellular adenoma and carcinoma) growths. Results In the hepatitic liver (chronic hepatitic/cirrhosis, hepatocellular nodules and HCC) we found widespread RASSF1A gene promoter methylation with a methylation index that increased from regenerative conditions (cirrhosis) to hepatocellular nodules (p < 0.01) to HCC (p < 0.001). In the non-hepatitic liver a consistent pattern of gene methylation was also found in both lesional (focal nodular hyperplasia and hepatocellular adenoma) and non-lesional tissue. Specifically, hepatocellular adenomas (HA) showed a methylation index significantly higher than that detected in focal nodular hyperplasia (FNH) (p < 0.01) and in non-lesional tissue (p < 0.001). In non-lesional liver also the methylation index gradually increased by ageing (p = 0.002), suggesting a progressive spreading of methylated cells over time. As opposed to RASSF1A gene promoter methylation, NORE1A gene was never found epigenetically alterated in both hepatitic and non-hepatitic liver. Conclusion We have shown that in non-lesional, regenerative and neoplastic liver the RASSF1A gene is increasingly

Serum amyloid A protein in amyloidosis, rheumatic, and neoplastic diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benson, M.D.; Cohen, A.S.

1979-01-01

Serum levels of amyloid protein A (SAA) have been shown to be elevated in different types of amyloidosis and in rheumatic diseases by radioimmunoassay using 125 iodine labeled AA and anti-AA. SAA levels were elevated in both primary and secondary amyloidosis, but there were highly significant differences between these levels. In heredofamilial amyloid, SAA levels were within normal limits. While the mean SAA level was elevated in persons over 70 years, the fact that some persons in this age group had normal levels suggested that marked elevation after age 70 may be due to occult inflammatory or neoplastic disease. Highmore » SAA levels in patients with rheumatoid arthritis correlated, in most cases, with physician evaluation of disease activity and Westergren ESR. SAA levels in patients with systemic lupus erythematosus were lower than those in patients with rheumatoid arthritis, and most patients with degenerative joint disease had normal levels. Very high levels of SAA were found in patients with neoplastic diseases. Patients with carcinoma of the lung and bowel had much higher levels than patients with carcinoma of the breast. Determination of SAA levels may be of value in evaluating different forms of systemic amyloidosis, assessing the activity of rheumatic disease, and screening for occult inflammatory or neoplastic disease.« less

Acinar cell cystadenoma of the pancreas: a benign neoplasm or non-neoplastic ballooning of acinar and ductal epithelium?

PubMed

Singhi, Aatur D; Norwood, Stephanie; Liu, Ta-Chiang; Sharma, Rajni; Wolfgang, Christopher L; Schulick, Richard D; Zeh, Herbert J; Hruban, Ralph H

2013-09-01

Acinar cell cystadenoma (ACA) of the pancreas was initially described as a non-neoplastic cyst of the pancreas and, at that time, referred to as "acinar cystic transformation." In subsequent studies, these lesions were given the designation of "-oma," despite the relative lack of evidence supporting a neoplastic process. To characterize these lesions further, we examined the clinical, pathologic, and immunohistochemical features of 8 ACAs. The majority of patients were female (7 of 8, 88%) and ranged in age from 18 to 57 years (mean, 43 y). Grossly, the cysts involved the head (n=5), body (n=1), or the entire pancreas (n=2). ACAs were either multilocular (n=4) or unilocular (n=4) and ranged in size from 1.8 to 15 cm (mean, 6.8 cm). Histologically, multilocular ACAs were lined by patches of acinar and ductal epithelium. Immunolabeling, including double-labeling for cytokeratin 19 and chymotrypsin, highlighted the patchy pattern of the ductal and acinar cells lining the cysts. In some areas, the cysts with patches of acinar and ductal differentiation formed larger locules with incomplete septa as they appeared to fuse with other cysts. In contrast, the unilocular cases were lined by 1 to 2 cell layers of acinar cells with little intervening ductal epithelium. Nuclear atypia, mitotic figures, necrosis, infiltrative growth, and associated invasive carcinoma were absent in all cases. In addition, we assessed the clonal versus polyclonal nature of ACAs, occurring in women, using X-chromosome inactivation analysis of the human androgen receptor (AR) gene. Five of 7 cases were informative and demonstrated a random X-chromosome inactivation pattern. Clinical follow-up information was available for all patients, and follow-up ranged from 10 months to 7.8 years (mean, 3.6 y), with no evidence of recurrence or malignant transformation. We hypothesize that early lesions are marked by acinar dilatation that expands into and incorporates smaller ductules and later larger ducts

Can endoscopic ultrasonography differentiate nonneoplastic from neoplastic gallbladder polyps?

PubMed

Akatsu, Tomotaka; Aiura, Koichi; Shimazu, Motohide; Ueda, Masakazu; Wakabayashi, Go; Tanabe, Minoru; Kawachi, Shigeyuki; Kitajima, Masaki

2006-02-01

The present study aimed to clarify the endoscopic ultrasonography (EUS) features of nonneoplastic (cholesterol polyps and adenomyomatosis) and neoplastic (adenoma and adenocarcinoma) gallbladder polyps and to evaluate the effectiveness and limitation of EUS in the differential diagnosis of these lesions. We retrospectively compared EUS images with histologic findings in 29 surgical cases with gallbladder polyps with a diameter of 10 to 20 mm. Those cases were indicated for surgery based on the findings of a sessile appearance, a solitary lesion, low echogenicity, and/or a lobulated surface. Six of 10 cholesterol polyps were atypically seen as partially or completely hypoechoic due to predominant proliferation of glandular epithelia. Nine of 10 cholesterol polyps demonstrated an aggregation of hyperechoic spots, which represented multiple granules of cholesterosis. All adenomyomatoses (n = 10) showed multiple microcysts, which corresponded to proliferated Rokitansky-Aschoff sinuses. However, three of nine neoplastic lesions (three adenomas and six adenocarcinomas) showed one of these signs due to concomitant cholesterosis (n = 2) or proliferated Rokitansky-Aschoff sinuses (n = 1). In conclusion, 69% (20/29) of gallbladder polyps larger than 10 mm that were preoperatively suspected of malignancy were nonneoplastic. An aggregation of hyperechoic spots and multiple microcysts are considered to be important predictive factors for cholesterol polyps and adenomyomatosis, respectively. However, we should caution that these findings can also occur in neoplastic polyps when they contain a concomitant nonneoplastic component (cholesterosis or proliferated Rokitansky-Aschoff sinuses).

Cervical (pre)neoplastic microenvironment promotes the emergence of tolerogenic dendritic cells via RANKL secretion

PubMed Central

Demoulin, Stéphanie A; Somja, Joan; Duray, Anaëlle; Guénin, Samuel; Roncarati, Patrick; Delvenne, Philippe O; Herfs, Michael F; Hubert, Pascale M

2015-01-01

The progression of genital human papillomavirus (HPV) infections into preneoplastic lesions suggests that infected/malignant cells are not adequately recognized by the immune system. In this study, we demonstrated that cervical/vulvar cancer cells secrete factor(s) that affect both the maturation and function of dendritic cells (DC) leading to a tolerogenic profile. Indeed, DC cocultured with cancer cell lines display both a partially mature phenotype after lipopolysaccharide (LPS) maturation and an altered secretory profile (IL-10high and IL-12p70low). In addition, tumor-converted DC acquire the ability to alter T-cell proliferation and to induce FoxP3+ suppressive T cells from naive CD4+ T cells. Among the immunosuppressive factors implicated in DC alterations in genital (pre)neoplastic microenvironment, we identified receptor activator of nuclear factor kappa-B ligand (RANKL), a TNF family member, as a potential candidate. For the first time, we showed that RANKL expression strongly increases during cervical progression. We also confirmed that RANKL is directly secreted by cancer cells and this expression is not related to HPV viral oncoprotein induction. Interestingly, the addition of osteoprotegerin (OPG) in coculture experiments reduces significantly the inhibition of DC maturation, the release of a tolerogenic cytokine profile (IL-12low IL-10high) and the induction of regulatory T (Treg) cells. Our findings suggest that the use of inhibitory molecules directed against RANKL in cervical/vulvar (pre)neoplastic lesions might prevent alterations of DC functionality and represent an attractive strategy to overcome immune tolerance in such cancers. PMID:26155412

The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Yu; Wong, Nicholas; Guan, Yinghui

2008-04-25

Ovarian epithelial carcinomas (OEC) frequently exhibit amplifications at the 20q13 locus which is the site of several oncogenes, including the eukaryotic elongation factor EEF1A2 and the transcription factor ZNF217. We reported previously that overexpressed ZNF217 induces neoplastic characteristics in precursor cells of OEC. Unexpectedly, ZNF217, which is a transcriptional repressor, enhanced expression of eEF1A2. In this study, array comparative genomic hybridization, single nucleotide polymorphism and Affymetrix analysis of ZNF217-overexpressing cell lines confirmed consistently increased expression of eEF1A2 but not of other oncogenes, and revealed early changes in EEF1A2 gene copy numbers and increased expression at crisis during immortalization. We definedmore » the influence of eEF1A2 overexpression on immortalized ovarian surface epithelial cells, and investigated interrelationships between effects of ZNF217 and eEF1A2 on cellular phenotypes. Lentivirally induced eEF1A2 overexpression caused delayed crisis, apoptosis resistance and increases in serum-independence, saturation densities, and anchorage independence. siRNA to eEF1A2 reversed apoptosis resistance and reduced anchorage independence in eEF1A2-overexpressing lines. Remarkably, siRNA to eEF1A2 was equally efficient in inhibiting both anchorage independence and resistance to apoptosis conferred by ZNF217 overexpression. Our data define neoplastic properties that are caused by eEF1A2 in nontumorigenic ovarian cancer precursor cells, and suggest that eEF1A2 plays a role in mediating ZNF217-induced neoplastic progression.« less

[Detection of early neoplasia in Barrett's oesophagus: focus attention on index endoscopy in short-segment-Barrett's oesophagus with random biopsies].

PubMed

Behrens, A; Pech, O; Wuthnow, E; Manner, H; Pohl, J; May, A; Ell, C

2015-06-01

Detecting early neoplasias in Barrett's oesophagus (BE) is challenging. Recent publications have been focusing on improving the detection of such lesions during Barrett's surveillance. However in a recently published Danish register study calculating the risk for cancer-development in BE two-thirds of the diagnosed tumors were identified during the first examination or in the first year. This means that index endoscopy might be more effective than surveillance in detecting early neoplasia in BE.  In the period from January 2010 to April 2011, all patients who consecutively presented with a diagnosis of early neoplastic changes in BE were recorded prospectively. The analysis included data for 121 patients. In patients with short-segment BE (SSBE), neoplasia was only diagnosed in 6 % of cases in the surveillance examination, compared with 44 % of cases in long-segment BE (LSBE). The neoplastic lesion was identified visually in 43 patients (36 %) during the external EGD. Type II tumours were detected in 40 % (39/98) and were correctly assessed as neoplastic in 25 % of cases (24/98). 1. in patients with SSBE almost all early tumours are diagnosed by index endoscopy and not by Barrett's surveillance; 2. around 40 % of all early neoplasias are endoscopically invisible and are only diagnosed using four-quadrant biopsies; 3. the macroscopic tumour type has a substantial influence on the detection rate for neoplasia. If efforts to increase the detection rate for early neoplasia in BE are focused solely on the Barrett's surveillance method, then only a minority of patients - 20 % in the present group - will benefit from the measure. German clinical trials register, DRKS00 004 168. © Georg Thieme Verlag KG Stuttgart · New York.

Control of apoptosis by Drosophila DCAF12.

PubMed

Hwangbo, Dae-Sung; Biteau, Benoit; Rath, Sneha; Kim, Jihyun; Jasper, Heinrich

2016-05-01

Regulated Apoptosis (Programmed Cell Death, PCD) maintains tissue homeostasis in adults, and ensures proper growth and morphogenesis of tissues during development of metazoans. Accordingly, defects in cellular processes triggering or executing apoptotic programs have been implicated in a variety of degenerative and neoplastic diseases. Here, we report the identification of DCAF12, an evolutionary conserved member of the WD40-motif repeat family of proteins, as a new regulator of apoptosis in Drosophila. We find that DCAF12 is required for Diap1 cleavage in response to pro-apoptotic signals, and is thus necessary and sufficient for RHG (Reaper, Hid, and Grim)-mediated apoptosis. Loss of DCAF12 perturbs the elimination of supernumerary or proliferation-impaired cells during development, and enhances tumor growth induced by loss of neoplastic tumor suppressors, highlighting the wide requirement for DCAF12 in PCD. Copyright © 2016 Elsevier Inc. All rights reserved.

Oceanographic Changes through the Early Triassic Crisis Interval

NASA Astrophysics Data System (ADS)

Algeo, T. J.

2013-12-01

Recent studies of diverse paleoceanographic proxies have provided the basis for reconstructing in some detail oceanographic changes during the end-Permian mass extinction and through the ~5-million-year-long Early Triassic crisis interval. Conodont δ18O records have demonstrated strong warming, to tropical sea-surface temperatures as high as 40oC, during the Griesbachian to Dienerian substages1-2. The crisis interval also was associated with major perturbations in the marine carbon and sulfur cycles. Three episodes of strong warming coincided with decreases in marine carbonate δ13C and marine sulfate δ34S 3, as well as increases in Δδ13Cvert4 and enhanced subaerial weathering fluxes5-6. Lower δ13Ccarb and δ34Ssulf values are indicative of more limited burial of reduced C and S in organic carbon and pyrite, consistent with declines in marine productivity and bacterial sulfate reduction3. Increased Δδ13Cvert is indicative of intensified stratification of the oceanic water column4, and increased subaerial weathering fluxes probably reflect higher soil reaction rates and possibly an intensified hydrologic cycle5-6. Collectively, these patterns are indicative of the globally integrated response of marine and terrestrial regimes to episodic perturbations in the form of extreme warming events1-2,7. These warming events may have been triggered by major volcanic eruptions8, as suggested by recent studies of volcanic ash layers9-10 and rare earth elements11 in South China P-Tr boundary sections. The ~2-million-year-long Early Triassic interval of extreme sea-surface temperatures came to an abrupt end around the Smithian-Spathian boundary1-2. Cooling coincided with a sharp decline in Δδ13Cvert due to stronger vertical overturning circulation4 and a major positive excursion in δ13Ccarb due to increased marine productivity related to greater mixing of nutrients into the ocean-surface layer12. The late Spathian was characterized by a final, weaker episode of sea

The pilot study assessing efficacy and versatility of novel therapy for neoplastic ulceration: clinical and microbiological aspects

PubMed Central

Tomaszewska, Elżbieta; Muszyński, Zygmunt; Ciupińska, Maria; Kotlińska-Lemieszek, Aleksandra

2013-01-01

Introduction Neoplastic ulcers are chronic and, most often, irreversible lesions caused by proliferation of tumor cells infiltrating and damaging skin tissues. The treatment of neoplastic ulcers is a very difficult and time-consuming process. So, is very important to find methods of controlling this type of chronic wounds. Aim To evaluate the efficiency of monitored treatment of neoplastic ulcers by means of providing moist wound environment dressings and antiseptic to the group of patients with an advanced stage of tumor, with particular focus on the impact of the treatment applied on the clinical condition of the ulcers; to evaluate the impact of the treatment applied on the dynamics of bacterial flora in neoplastic ulcers, with particular focus on the presence of alarm pathogens; to conduct a risk analysis of the occurrence of local and systemic complications during treatment. Material and methods This was a prospective pilot clinical study of 30 patients with malignant ulcers, 13 male and 17 female aged from 24 to 92 years treated with octenidine antiseptic and dressing set for 3 weeks. The wounds were clinically assessed for the changes of amount of necrotic tissue, exudate level and type, malodour and pain level during treatment. At the baseline and after 3 weeks of treatment, the wounds were swabbed for microbiological assessment. Results The used scheme of treatment is efficient and brings clinical improvement in all treated ulcers. During the 3-week treatment, reduction of necrotic tissue, decrease in the level of exudate, pain and malodour was observed in all patients (p < 0.05). High activity of octenidine against Gram(–) and Gram(+) bacteria was observed. The use of octenidine dihydrochloride correlated with a progressing eradication of multiresistant strains and alarm pathogens (p < 0.001). No serious adverse effects or significant symptoms of intolerance of the applied treatment were observed. PMID:24278081

High-resolution sonography for distinguishing neoplastic gallbladder polyps and staging gallbladder cancer.

PubMed

Kim, Jung Hoon; Lee, Jae Young; Baek, Jee Hyun; Eun, Hyo Won; Kim, Young Jae; Han, Joon Koo; Choi, Byung Ihn

2015-02-01

OBJECTIVE. The purposes of this study were to compare staging accuracy of high-resolution sonography (HRUS) with combined low- and high-MHz transducers with that of conventional sonography for gallbladder cancer and to investigate the differences in the imaging findings of neoplastic and nonneoplastic gallbladder polyps. MATERIALS AND METHODS. Our study included 37 surgically proven gallbladder cancer (T1a = 7, T1b = 2, T2 = 22, T3 = 6), including 15 malignant neoplastic polyps and 73 surgically proven polyps (neoplastic = 31, nonneoplastic = 42) that underwent HRUS and conventional transabdominal sonography. Two radiologists assessed T-category and predefined polyp findings on HRUS and conventional transabdominal sonography. Statistical analyses were performed using chi-square and McNemar tests. RESULTS. The diagnostic accuracy for the T category was T1a = 92-95%, T1b = 89-95%, T2 = 78-86%, and T3 = 84-89%, all with good agreement (κ = 0.642) using HRUS. The diagnostic accuracy for differentiating T1 from T2 or greater than T2 was 92% and 89% on HRUS and 65% and 70% with conventional transabdominal sonography. Statistically common findings for neoplastic polyps included size greater than 1 cm, single lobular surface, vascular core, hypoechoic polyp, and hypoechoic foci (p < 0.05). The value of HRUS in the differential diagnosis of a gallbladder polyp was more clearly depicted internal echo foci than conventional transabdominal sonography (39 vs 21). A polyp size greater than 1 cm was independently associated with a neoplastic polyp (odds ratio = 7.5, p = 0.02). The AUC of a polyp size greater than 1 cm was 0.877. The sensitivity and specificity were 66.67% and 89.13%, respectively. CONCLUSION. HRUS is a simple method that enables accurate T categorization of gallbladder carcinoma. It provides high-resolution images of gallbladder polyps and may have a role in stratifying the risk for malignancy.

Nuclear Factor kappa B is central to Marek’s Disease herpesvirus induced neoplastic transformation of CD30 expressing lymphocytes in-vivo

PubMed Central

2012-01-01

Background Marek’s Disease (MD) is a hyperproliferative, lymphomatous, neoplastic disease of chickens caused by the oncogenic Gallid herpesvirus type 2 (GaHV-2; MDV). Like several human lymphomas the neoplastic MD lymphoma cells overexpress the CD30 antigen (CD30hi) and are in minority, while the non-neoplastic cells (CD30lo) form the majority of population. MD is a unique natural in-vivo model of human CD30hi lymphomas with both natural CD30hi lymphomagenesis and spontaneous regression. The exact mechanism of neoplastic transformation from CD30lo expressing phenotype to CD30hi expressing neoplastic phenotype is unknown. Here, using microarray, proteomics and Systems Biology modeling; we compare the global gene expression of CD30lo and CD30hi cells to identify key pathways of neoplastic transformation. We propose and test a specific mechanism of neoplastic transformation, and genetic resistance, involving the MDV oncogene Meq, host gene products of the Nuclear Factor Kappa B (NF-κB) family and CD30; we also identify a novel Meq protein interactome. Results Our results show that a) CD30lo lymphocytes are pre-neoplastic precursors and not merely reactive lymphocytes; b) multiple transformation mechanisms exist and are potentially controlled by Meq; c) Meq can drive a feed-forward cycle that induces CD30 transcription, increases CD30 signaling which activates NF-κB, and, in turn, increases Meq transcription; d) Meq transcriptional repression or activation of the CD30 promoter generally correlates with polymorphisms in the CD30 promoter distinguishing MD-lymphoma resistant and susceptible chicken genotypes e) MDV oncoprotein Meq interacts with proteins involved in physiological processes central to lymphomagenesis. Conclusions In the context of the MD lymphoma microenvironment (and potentially in other CD30hi lymphomas as well), our results show that the neoplastic transformation is a continuum and the non-neoplastic cells are actually pre-neoplastic precursor

[Carcinogenesis and its mechanism of mutant-type[12Asp]K-ras4B gene].

PubMed

Gui, Li-ming; Wei, Li-hui; Zhang, Ying-mei; Wang, Jian-liu; Wang, Ying; Chen, Ying; Ma, Da-long

2002-01-01

Ras gene plays an important role in the extra- and intra-cellular signal transduction pathway. It mediates series cascade reactions, and eventually actives transcriptional factors in nucleus. It is unknown on the mechanism of carcinogenesis of Ras gene in endometrial carcinoma, though K-ras mutant is very common in endometrial atypical hyperplasia and carcinoma. On basis of discovering the mutation in 12th codon of K-ras in endometrial carcinoma cell line, HEC-1A, we explored the carcinogenesis and molecular mechanism of mutant-type [12Asp] K-ras4B gene. (1) Full-length [12Asp]K-ras4B cDNA was amplified with RT-PCR, then inserted into pcDI eukaryotic expressive vector. (2) Morphological change, growth kinetics in vitro and tumorigencity in nude mice in vivo after-before transfection were observed. (3) To test the cell growth kinetics by methyl thiazolium tetrazolium (MTT) and [3H]thymidine incorporation method. (1) The authors have successfully constructed eukaryotic expression plasmid pcDI-[12Asp] K-ras4B; (2) To confirm that [12Asp] K-ras4B mutant can trigger the neoplastic transformation of NIH3T3 cells by test in vitro and in vivo. (3) After pMCV-RasN17 plasmid, a Ras mutant were transfected into pcDI-[12Asp] K-ras4B cells, the growth of this cell were restrained significantly in comparison with control group. (4) These findings indicate the expression of RafS621A resulted in remarkable inhibition in proliferation of pcDI-[12Asp]K-ras4B cell (P < 0.05). However, RafCAAX mutant can enhance pcDI-[12Asp]K-ras4B cell growth (P < 0.05). (1) [12Asp]K-ras4B gene alone is able to cause neoplastic transformation in NIH3T3 cells in vitro and in vivo. (2) [12Asp]K-ras4B-induced NIH3T3 cells neoplastic transformation required Raf signaling pathway.

Telomere length in normal and neoplastic canine tissues.

PubMed

Cadile, Casey D; Kitchell, Barbara E; Newman, Rebecca G; Biller, Barbara J; Hetler, Elizabeth R

2007-12-01

To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues. 57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs. Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois. Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length. Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human anti-telomerase strategies.

Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions.

PubMed

Beger, Hans G; Schwarz, Michael; Poch, Bertram

2012-11-01

Cystic neoplasms of the pancreas are diagnosed frequently due to early use of abdominal imaging techniques. Intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and serous pseudopapillary neoplasia are considered pre-cancerous lesions because of frequent transformation to cancer. Complete surgical resection of the benign lesion is a pancreatic cancer preventive treatment. The application for a limited surgical resection for the benign lesions is increasingly used to reduce the surgical trauma with a short- and long-term benefit compared to major surgical procedures. Duodenum-preserving total pancreatic head resection introduced for inflammatory tumors in the pancreatic head transfers to the patient with a benign cystic lesion located in the pancreatic head, the advantages of a minimalized surgical treatment. Based on the experience of 17 patients treated for cystic neoplastic lesions with duodenum-preserving total pancreatic head resection, the surgical technique of total pancreatic head resection for adenoma, borderline tumors, and carcinoma in situ of cystic neoplasm is presented. A segmental resection of the peripapillary duodenum is recommended in case of suspected tissue ischemia of the peripapillary duodenum. In 305 patients, collected from the literature by PubMed search, in about 40% of the patients a segmental resection of the duodenum and 60% a duodenum and common bile duct-preserving total pancreatic head resection has been performed. Hospital mortality of the 17 patients was 0%. In 305 patients collected, the hospital mortality was 0.65%, 13.2% experienced a delay of gastric emptying and a pancreatic fistula in 18.2%. Recurrence of the disease was 1.5%. Thirty-two of 175 patients had carcinoma in situ. Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions is a safe surgical procedure with low post-operative morbidity and mortality.

Importance of Absent Neoplastic Epithelium in Patients Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

PubMed

Enblad, Malin; Birgisson, Helgi; Wanders, Alkwin; Sköldberg, Filip; Ghanipour, Lana; Graf, Wilhelm

2016-04-01

The importance of absent neoplastic epithelium in specimens from cytoreductive surgery (CRS) is unknown. This study aimed to investigate the prevalence and prognostic value of histopathology without neoplastic epithelium in patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Data were extracted from medical records and histopathology reports for patients treated with initial CRS and HIPEC at Uppsala University Hospital, Sweden, between 2004 and 2012. Patients with inoperable disease and patients undergoing palliative non-CRS surgery were excluded from the study. Patients lacking neoplastic epithelium in surgical specimens from CRS, with or without mucin, were classified as "neoplastic epithelium absent" (NEA), and patients with neoplastic epithelium were classified as "neoplastic epithelium present" (NEP). The study observed NEA in 78 of 353 patients (22 %). Mucin was found in 28 of the patients with NEA. For low-grade appendiceal mucinous neoplasms and adenomas, the 5-year overall survival rate was 100 % for NEA and 84 % for NEP, and the 5-year recurrence-free survival rate was 100 % for NEA and 59 % for NEP. For appendiceal/colorectal adenocarcinomas (including tumors of the small intestine), the 5-year overall survival rate was 61 % for NEA and 38 % for NEP, and the 5-year recurrence-free survival rate was 60 % for NEA and 14 % for NEP. Carcinoembryonic antigen level, peritoneal cancer index, and completeness of the cytoreduction score were lower in patients with NEA. A substantial proportion of patients undergoing CRS and HIPEC have NEA. These patients have a favorable prognosis and a decreased risk of recurrence. Differences in patient selection can affect the proportion of NEA and hence explain differences in survival rates between reported series.

Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.

PubMed

Haycock, Philip C; Burgess, Stephen; Nounu, Aayah; Zheng, Jie; Okoli, George N; Bowden, Jack; Wade, Kaitlin Hazel; Timpson, Nicholas J; Evans, David M; Willeit, Peter; Aviv, Abraham; Gaunt, Tom R; Hemani, Gibran; Mangino, Massimo; Ellis, Hayley Patricia; Kurian, Kathreena M; Pooley, Karen A; Eeles, Rosalind A; Lee, Jeffrey E; Fang, Shenying; Chen, Wei V; Law, Matthew H; Bowdler, Lisa M; Iles, Mark M; Yang, Qiong; Worrall, Bradford B; Markus, Hugh Stephen; Hung, Rayjean J; Amos, Chris I; Spurdle, Amanda B; Thompson, Deborah J; O'Mara, Tracy A; Wolpin, Brian; Amundadottir, Laufey; Stolzenberg-Solomon, Rachael; Trichopoulou, Antonia; Onland-Moret, N Charlotte; Lund, Eiliv; Duell, Eric J; Canzian, Federico; Severi, Gianluca; Overvad, Kim; Gunter, Marc J; Tumino, Rosario; Svenson, Ulrika; van Rij, Andre; Baas, Annette F; Bown, Matthew J; Samani, Nilesh J; van t'Hof, Femke N G; Tromp, Gerard; Jones, Gregory T; Kuivaniemi, Helena; Elmore, James R; Johansson, Mattias; Mckay, James; Scelo, Ghislaine; Carreras-Torres, Robert; Gaborieau, Valerie; Brennan, Paul; Bracci, Paige M; Neale, Rachel E; Olson, Sara H; Gallinger, Steven; Li, Donghui; Petersen, Gloria M; Risch, Harvey A; Klein, Alison P; Han, Jiali; Abnet, Christian C; Freedman, Neal D; Taylor, Philip R; Maris, John M; Aben, Katja K; Kiemeney, Lambertus A; Vermeulen, Sita H; Wiencke, John K; Walsh, Kyle M; Wrensch, Margaret; Rice, Terri; Turnbull, Clare; Litchfield, Kevin; Paternoster, Lavinia; Standl, Marie; Abecasis, Gonçalo R; SanGiovanni, John Paul; Li, Yong; Mijatovic, Vladan; Sapkota, Yadav; Low, Siew-Kee; Zondervan, Krina T; Montgomery, Grant W; Nyholt, Dale R; van Heel, David A; Hunt, Karen; Arking, Dan E; Ashar, Foram N; Sotoodehnia, Nona; Woo, Daniel; Rosand, Jonathan; Comeau, Mary E; Brown, W Mark; Silverman, Edwin K; Hokanson, John E; Cho, Michael H; Hui, Jennie; Ferreira, Manuel A; Thompson, Philip J; Morrison, Alanna C; Felix, Janine F; Smith, Nicholas L; Christiano, Angela M; Petukhova, Lynn; Betz, Regina C; Fan, Xing; Zhang, Xuejun; Zhu, Caihong; Langefeld, Carl D; Thompson, Susan D; Wang, Feijie; Lin, Xu; Schwartz, David A; Fingerlin, Tasha; Rotter, Jerome I; Cotch, Mary Frances; Jensen, Richard A; Munz, Matthias; Dommisch, Henrik; Schaefer, Arne S; Han, Fang; Ollila, Hanna M; Hillary, Ryan P; Albagha, Omar; Ralston, Stuart H; Zeng, Chenjie; Zheng, Wei; Shu, Xiao-Ou; Reis, Andre; Uebe, Steffen; Hüffmeier, Ulrike; Kawamura, Yoshiya; Otowa, Takeshi; Sasaki, Tsukasa; Hibberd, Martin Lloyd; Davila, Sonia; Xie, Gang; Siminovitch, Katherine; Bei, Jin-Xin; Zeng, Yi-Xin; Försti, Asta; Chen, Bowang; Landi, Stefano; Franke, Andre; Fischer, Annegret; Ellinghaus, David; Flores, Carlos; Noth, Imre; Ma, Shwu-Fan; Foo, Jia Nee; Liu, Jianjun; Kim, Jong-Won; Cox, David G; Delattre, Olivier; Mirabeau, Olivier; Skibola, Christine F; Tang, Clara S; Garcia-Barcelo, Merce; Chang, Kai-Ping; Su, Wen-Hui; Chang, Yu-Sun; Martin, Nicholas G; Gordon, Scott; Wade, Tracey D; Lee, Chaeyoung; Kubo, Michiaki; Cha, Pei-Chieng; Nakamura, Yusuke; Levy, Daniel; Kimura, Masayuki; Hwang, Shih-Jen; Hunt, Steven; Spector, Tim; Soranzo, Nicole; Manichaikul, Ani W; Barr, R Graham; Kahali, Bratati; Speliotes, Elizabeth; Yerges-Armstrong, Laura M; Cheng, Ching-Yu; Jonas, Jost B; Wong, Tien Yin; Fogh, Isabella; Lin, Kuang; Powell, John F; Rice, Kenneth; Relton, Caroline L; Martin, Richard M; Davey Smith, George

2017-05-01

The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Genomewide association studies (GWAS) published up to January 15, 2015. GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of

Prevalence of Neoplastic Diseases in Pet Birds Referred for Surgical Procedures

PubMed Central

Castro, Patrícia F.; Fantoni, Denise T.; Miranda, Bruna C.; Matera, Julia M.

2016-01-01

Neoplastic disease is common in pet birds, particularly in psittacines, and treatment should be primarily aimed at tumor eradication. Nineteen cases of pet birds submitted to diagnostic and/or therapeutic surgical procedures due to neoplastic disease characterized by the presence of visible masses were retrospectively analyzed; affected species, types of neoplasms and respective locations, and outcomes of surgical procedures were determined. All birds undergoing surgery belonged to the order Psittaciformes; the Blue-fronted parrot (Amazona aestiva) was the prevalent species. Lipoma was the most frequent neoplasm in the sample studied. Most neoplasms affected the integumentary system, particularly the pericloacal area. Tumor resection was the most common surgical procedure performed, with high resolution and low recurrence rates. PMID:26981315

[Non-neoplastic enlargement of salivary glands: clinico-histologic analysis].

PubMed

González Guevara, Martha Beatriz; Torres Tejero, Marco Antonio; Martínez Mata, Guillermo

2005-01-01

We carried out a retrospective study on non-neoplastic enlargement of the salivary glands at the Oral Histopathology Diagnostic Center of the Autonomous Metropolitan University at Xochimilco (UAM-Xochimilco) in Mexico during a period of 24 years (1979-2003). From 5,625 biopsies received and analyzed, a total of 461 (8.2%) were non-neoplastic enlargement of the salivary glands; for each case, we registered demographic data as well as clinic characteristics. These lesions were characterized as a heterogeneous group of pathologic entities among which we included local, obstructive, infectious, and immunopathologic lesions. The most frequent lesion was the extravasation cyst in 341 (74%) cases, followed by chronic sialoadenitis and Sjögren's syndrome with 54 (11.7%) and 41 (8.8%) cases, respectively, and at a lesser percentage mucous retention cyst, sialosis, benign lymphoepithelial lesions and those related with sialolytes. Females were affected more frequently; mean age was second to third life decades. These lesions were most frequently localized on inferior labial mucosa.

Apoptosis: its role in pituitary development and neoplastic pituitary tissue.

PubMed

Guzzo, M F; Carvalho, L R S; Bronstein, M D

2014-04-01

Apoptosis, also known as programmed cell death, is a phenomenon in which different stimuli trigger cellular mechanisms that culminate in death, in the absence of inflammatory cell response. Two different activation pathways are known, the intrinsic pathway (or mitochondrial) and extrinsic (or death-receptor pathway), both pathways trigger enzymatic reactions that lead cells to break up and be phagocytized by neighboring cells. This process is a common occurrence in physiological and pathological states, participating in the control of cell proliferation, differentiation and remodeling of organs. In the early steps of pituitary gland formation, numerous apoptotic cells are detected in the separation of Rathke's pouch from the roof of oral ectoderm. In the distal part of the gland, which will form the adenohypophysis, the ratio of apoptosis was significantly lower. However, there is evidence that neoplastic pituitary cells undergo unbalance in genes that control apoptosis leading to uncontrolled cell growth. No direct evidence of apoptosis was found in the drugs used for tumors producing prolactin and growth hormone. In conclusion, an unbalancing in the apoptosis process is the boundary between development and tumor growth.

Pycnogenol reduces talc-induced neoplastic transformation in human ovarian cell cultures.

PubMed

Buz'Zard, Amber R; Lau, Benjamin H S

2007-06-01

Talc and poor diet have been suggested to increase the risk of developing ovarian cancer; which can be reduced by a diet rich in fruit and vegetables. Talc is ubiquitous despite concern about its safety, role as a possible carcinogen and known ability to cause irritation and inflammation. It was recently shown that Pycnogenol (Pyc; a proprietary mixture of water-soluble bioflavonoids extracted from French maritime pine bark) was selectively toxic to established malignant ovarian germ cells. This study investigated talc-induced carcinogenesis and Pyc-induced chemoprevention. Normal human epithelial and granulosa ovarian cell lines and polymorphonuclear neutrophils (PMN) were treated with talc, or pretreated with Pyc then talc. Cell viability, reactive oxygen species (ROS) generation and neoplastic transformation by soft agar assay were measured. Talc increased proliferation, induced neoplastic transformation and increased ROS generation time-dependently in the ovarian cells and dose-dependently in the PMN. Pretreatment with Pyc inhibited the talc-induced increase in proliferation, decreased the number of transformed colonies and decreased the ROS generation in the ovarian cells. The data suggest that talc may contribute to ovarian neoplastic transformation and Pyc reduced the talc-induced transformation. Taken together, Pyc may prove to be a potent chemopreventative agent against ovarian carcinogenesis. (c) 2007 John Wiley & Sons, Ltd.

12 CFR 1024.39 - Early intervention requirements for certain borrowers.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 8 2014-01-01 2014-01-01 false Early intervention requirements for certain... SETTLEMENT PROCEDURES ACT (REGULATION X) Mortgage Servicing § 1024.39 Early intervention requirements for... of the user, the revised text is set forth as follows: § 1024.39 Early intervention requirements for...

15 CFR 10.12 - Editorial changes.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Editorial changes. 10.12 Section 10.12... PRODUCT STANDARDS § 10.12 Editorial changes. The Department may, without prior notice, make such editorial or other minor changes as it deems necessary to reduce ambiguity or to improve clarity in any...

In vitro early changes in intercellular junctions by treatment with a chemical carcinogen.

PubMed

Tachikawa, T; Kohno, Y; Matsui, Y; Yoshiki, S

1986-06-01

To examine early intercellular junction changes caused by treatment with 9,10-dimethyl-1,2-benzanthracene (DMBA), rat lingual epithelium was cultivated in isolation and observed by electrophysiological, freeze-fracture and whole-mount electron microscopy. Electrophysiological measurements showed a transient decrease in membrane potential of -10.2 mV 6 h after the treatment. It returned to almost the same level as that of the control group 1 day later. Six hours after treatment, input resistance decreased rapidly to 5.3 M omega but increased to 18.0 M omega 12 h after treatment. Transient reduction of input resistance and membrane potential occurred prior to the decrease in the coupling ratio 6 h after treatment with DMBA. In freeze-fracture replicas, the number of gap junctions decreased by approximately 45% of the control value 6 h after treatment with DMBA. At 12 h and thereafter, the number and area of gap junctions subsequently decreased by 60-80% of the control value. Alterations in the number and area of desmosomes were similar to those of the gap junctions. The formation of epithelial cytoskeletons, partially devoid of the 2-4 and 5-8 nm filaments was also observed. A decrease in the density of filament networks beneath the plasma membranes was especially apparent. Treatment with a carcinogen brought about morphological cellular changes as early as 6 h after treatment, and such early changes might trigger metabolic cellular abnormalities. Affected cells appear to move away from normal cells in a process of repeated destruction and revision of intercellular junctions, and cytoskeletons.

DNA mismatch repair protein deficient non-neoplastic colonic crypts: a novel indicator of Lynch syndrome.

PubMed

Pai, Rish K; Dudley, Beth; Karloski, Eve; Brand, Randall E; O'Callaghan, Neil; Rosty, Christophe; Buchanan, Daniel D; Jenkins, Mark A; Thibodeau, Stephen N; French, Amy J; Lindor, Noralane M; Pai, Reetesh K

2018-06-08

Lynch syndrome is the most common form of hereditary colorectal carcinoma. However, establishing the diagnosis of Lynch syndrome is challenging, and ancillary studies that distinguish between sporadic DNA mismatch repair (MMR) protein deficiency and Lynch syndrome are needed, particularly when germline mutation studies are inconclusive. The aim of this study was to determine if MMR protein-deficient non-neoplastic intestinal crypts can help distinguish between patients with and without Lynch syndrome. We evaluated the expression of MMR proteins in non-neoplastic intestinal mucosa obtained from colorectal surgical resection specimens from patients with Lynch syndrome-associated colorectal carcinoma (n = 52) and patients with colorectal carcinoma without evidence of Lynch syndrome (n = 70), including sporadic MMR protein-deficient colorectal carcinoma (n = 30), MMR protein proficient colorectal carcinoma (n = 30), and "Lynch-like" syndrome (n = 10). MMR protein-deficient non-neoplastic colonic crypts were identified in 19 of 122 (16%) patients. MMR protein-deficient colonic crypts were identified in 18 of 52 (35%) patients with Lynch syndrome compared to only 1 of 70 (1%) patients without Lynch syndrome (p < 0.001). This one patient had "Lynch-like" syndrome and harbored two MSH2-deficient non-neoplastic colonic crypts. MMR protein-deficient non-neoplastic colonic crypts were not identified in patients with sporadic MMR protein-deficient or MMR protein proficient colorectal carcinoma. Our findings suggest that MMR protein-deficient colonic crypts are a novel indicator of Lynch syndrome, and evaluation for MMR protein-deficient crypts may be a helpful addition to Lynch syndrome diagnostics.

Chronic Trichuris muris infection causes neoplastic change in the intestine and exacerbates tumour formation in APC min/+ mice

PubMed Central

Cliffe, Laura J.; Bancroft, Alison J.; Forman, Simon P.; Thompson, Seona; Booth, Cath

2017-01-01

Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris) is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+) mice were infected with this parasite. Parasite infection in wild type mice led to the development of neoplastic change similar to that seen in mice that had been treated with the carcinogen azoxymethane. Additionally, both chronic and acute infection in the APCmin/+ mice led to an enhanced tumour development that was distinct to the site of infection suggesting systemic control. By blocking the parasite induced T regulatory response in these mice, the increase in the number of tumours following infection was abrogated. Thus T. muris infection alone causes an increase in gut pathologies that are known to be markers of cancer but also increases the incidence of tumour formation in a colon cancer model. The influence of parasitic worm infection on the development of cancer may therefore be significant. PMID:28650985

Chronic Trichuris muris infection causes neoplastic change in the intestine and exacerbates tumour formation in APC min/+ mice.

PubMed

Hayes, Kelly S; Cliffe, Laura J; Bancroft, Alison J; Forman, Simon P; Thompson, Seona; Booth, Cath; Grencis, Richard K

2017-06-01

Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris) is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+) mice were infected with this parasite. Parasite infection in wild type mice led to the development of neoplastic change similar to that seen in mice that had been treated with the carcinogen azoxymethane. Additionally, both chronic and acute infection in the APCmin/+ mice led to an enhanced tumour development that was distinct to the site of infection suggesting systemic control. By blocking the parasite induced T regulatory response in these mice, the increase in the number of tumours following infection was abrogated. Thus T. muris infection alone causes an increase in gut pathologies that are known to be markers of cancer but also increases the incidence of tumour formation in a colon cancer model. The influence of parasitic worm infection on the development of cancer may therefore be significant.

Big Five personality stability, change, and codevelopment across adolescence and early adulthood.

PubMed

Borghuis, Jeroen; Denissen, Jaap J A; Oberski, Daniel; Sijtsma, Klaas; Meeus, Wim H J; Branje, Susan; Koot, Hans M; Bleidorn, Wiebke

2017-10-01

Using data from 2 large and overlapping cohorts of Dutch adolescents, containing up to 7 waves of longitudinal data each (N = 2,230), the present study examined Big Five personality trait stability, change, and codevelopment in friendship and sibling dyads from age 12 to 22. Four findings stand out. First, the 1-year rank-order stability of personality traits was already substantial at age 12, increased strongly from early through middle adolescence, and remained rather stable during late adolescence and early adulthood. Second, we found linear mean-level increases in girls' conscientiousness, in both genders' agreeableness, and in boys' openness. We also found temporal dips (i.e., U-shaped mean-level change) in boys' conscientiousness and in girls' emotional stability and extraversion. We did not find a mean-level change in boys' emotional stability and extraversion, and we found an increase followed by a decrease in girls' openness. Third, adolescents showed substantial individual differences in the degree and direction of personality trait changes, especially with respect to conscientiousness, extraversion, and emotional stability. Fourth, we found no evidence for personality trait convergence, for correlated change, or for time-lagged partner effects in dyadic friendship and sibling relationships. This lack of evidence for dyadic codevelopment suggests that adolescent friends and siblings tend to change independently from each other and that their shared experiences do not have uniform influences on their personality traits. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

A rare neoplastic growth on the ear lobe.

PubMed

Rovere, R K; Hilgert, S F; da Costa, P Camara; de Lima, A S

2014-01-01

We report a case of an 83-year-old previously healthy female patient presenting with a swiftly evolving erythematous violaceous, infiltrative, ulcerated onion like mass with hyperkeratotic surface on the left ear lobe. The lesion was excised and resulted as an atypical fibroxanthoma, an extremely rare neoplastic growth, being a superficial variant of pleomorphic malignant fibrous histiocytoma. A brief review of dia-gnosis, treatment and prognosis is discussed.

Rapamycin attenuates BAFF-extended proliferation and survival via disruption of mTORC1/2 signaling in normal and neoplastic B-lymphoid cells.

PubMed

Zeng, Qingyu; Qin, Shanshan; Zhang, Hai; Liu, Beibei; Qin, Jiamin; Wang, Xiaoxue; Zhang, Ruijie; Liu, Chunxiao; Dong, Xiaoqing; Zhang, Shuangquan; Huang, Shile; Chen, Long

2018-01-01

B cell activating factor from the TNF family (BAFF) stimulates B-cell proliferation and survival, but excessive BAFF promotes the development of aggressive B cells leading to malignant and autoimmune diseases. Recently, we have reported that rapamycin, a macrocyclic lactone, attenuates human soluble BAFF (hsBAFF)-stimulated B-cell proliferation/survival by suppressing mTOR-mediated PP2A-Erk1/2 signaling pathway. Here, we show that the inhibitory effect of rapamycin on hsBAFF-promoted B cell proliferation/survival is also related to blocking hsBAFF-stimulated phosphorylation of Akt, S6K1, and 4E-BP1, as well as expression of survivin in normal and B-lymphoid (Raji and Daudi) cells. It appeared that both mTORC1 and mTORC2 were involved in the inhibitory activity of rapamycin, as silencing raptor or rictor enhanced rapamycin's suppression of hsBAFF-induced survivin expression and proliferation/viability in B cells. Also, PP242, an mTORC1/2 kinase inhibitor, repressed survivin expression, and cell proliferation/viability more potently than rapamycin (mTORC1 inhibitor) in B cells in response to hsBAFF. Of interest, ectopic expression of constitutively active Akt (myr-Akt) or constitutively active S6K1 (S6K1-ca), or downregulation of 4E-BP1 conferred resistance to rapamycin's attenuation of hsBAFF-induced survivin expression and B-cell proliferation/viability, whereas overexpression of dominant negative Akt (dn-Akt) or constitutively hypophosphorylated 4E-BP1 (4EBP1-5A), or downregulation of S6K1, or co-treatment with Akt inhibitor potentiated the inhibitory effects of rapamycin. The findings indicate that rapamycin attenuates excessive hsBAFF-induced cell proliferation/survival via blocking mTORC1/2 signaling in normal and neoplastic B-lymphoid cells. Our data underscore that rapamycin may be a potential agent for preventing excessive BAFF-evoked aggressive B-cell malignancies and autoimmune diseases. © 2017 Wiley Periodicals, Inc.

Early labour services: changes, triggers, monitoring and evaluation.

PubMed

Spiby, Helen; Green, Josephine M; Richardson-Foster, Helen; Hucknall, Clare

2013-04-01

to identify the changes to early labour services, their triggers and monitoring. a mixed methods approach in two stages, firstly a postal questionnaire survey of Heads of Midwifery (HoM) services in NHS Trusts in England (cover sheet to each HoM and questionnaire for each unit in their jurisdiction) and, secondly, semi-structured telephone interviews with a purposive sample of senior midwives. The interviews sought further information about reasons for change; the impact of changes and explored the unit's particular innovations. PARTICIPANTS AND RESPONSE RATE: 145 (89%) NHS Trusts provided data (cover sheet and/or questionnaire); responses were received from all areas and types of unit. Seventeen HoMs or designated senior midwives were interviewed. 83 of 170 units (49%) had made changes to early labour service provision during the past 5 years, including home assessment; the introduction of triage units and telephone assessment tools. Changes were more likely in high volume units and in consultant units with midwifery-led care areas. Further changes were planned by 93/178 (25%) units. Triggers for changes to early labour services comprised local or unit-based factors, including Category X (non-labour) admissions, response to service users and research evidence. The impact of Category X admissions on workload contributed to the triggers for change. Fifty-six (31%) could provide a confirmed figure or estimate for category X admissions. Experiences of introducing change included issues related to engagement of the workforce and the contribution of clinical leadership. Thirty-eight (48%) units did not routinely monitor use of early labour services. Overall monitoring of services was not significantly more likely in units that had made changes. Audit activity was reported more frequently in units that had made changes to their early labour services. early labour services had undergone significant changes following a range of triggers but the extent of change was not

Molecular evidence of viral DNA in non-small cell lung cancer and non-neoplastic lung

DOE PAGES

Robinson, Lary A.; Jaing, Crystal J.; Campbell, Christine Pierce; ...

2016-07-14

Although ~20% of human cancers are caused by microorganisms, only suspicion exists for a microbial cause of lung cancer. Potential infectious agents were investigated in non-small cell lung cancer (NSCLC) and non-neoplastic lung. Seventy NSCLC tumours (33 squamous cell carcinomas, 17 adenocarcinomas, 10 adenocarcinomas with lepidic spread, and 10 oligometastases) and 10 non-neoplastic lung specimens were evaluated for molecular evidence of microorganisms. Tissues were subjected to the Lawrence Livermore Microbial Detection Array, an oncovirus panel of the International Agency for Research on Cancer, and human papillomavirus (HPV) genotyping. Associations were examined between microbial prevalence, clinical characteristics, and p16 and EGFRmore » expression. Retroviral DNA was observed in 85% squamous cell carcinomas, 47% adenocarcinomas, and 10% adenocarcinomas with lepidic spread. Human papillomavirus DNA was found in 69% of squamous cell carcinomas with 30% containing high-risk HPV types. No significant viral DNA was detected in non-neoplastic lung. Patients with tumours containing viral DNA experienced improved long-term survival compared with patients with viral DNA-negative tumours. Lastly, most squamous cell carcinomas and adenocarcinomas contained retroviral DNA and one-third of squamous cell carcinomas contained high-risk HPV DNA. Viral DNA was absent in non-neoplastic lung. Trial results encourage further study of the viral contribution to lung carcinogenesis.« less

Molecular evidence of viral DNA in non-small cell lung cancer and non-neoplastic lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robinson, Lary A.; Jaing, Crystal J.; Campbell, Christine Pierce

Although ~20% of human cancers are caused by microorganisms, only suspicion exists for a microbial cause of lung cancer. Potential infectious agents were investigated in non-small cell lung cancer (NSCLC) and non-neoplastic lung. Seventy NSCLC tumours (33 squamous cell carcinomas, 17 adenocarcinomas, 10 adenocarcinomas with lepidic spread, and 10 oligometastases) and 10 non-neoplastic lung specimens were evaluated for molecular evidence of microorganisms. Tissues were subjected to the Lawrence Livermore Microbial Detection Array, an oncovirus panel of the International Agency for Research on Cancer, and human papillomavirus (HPV) genotyping. Associations were examined between microbial prevalence, clinical characteristics, and p16 and EGFRmore » expression. Retroviral DNA was observed in 85% squamous cell carcinomas, 47% adenocarcinomas, and 10% adenocarcinomas with lepidic spread. Human papillomavirus DNA was found in 69% of squamous cell carcinomas with 30% containing high-risk HPV types. No significant viral DNA was detected in non-neoplastic lung. Patients with tumours containing viral DNA experienced improved long-term survival compared with patients with viral DNA-negative tumours. Lastly, most squamous cell carcinomas and adenocarcinomas contained retroviral DNA and one-third of squamous cell carcinomas contained high-risk HPV DNA. Viral DNA was absent in non-neoplastic lung. Trial results encourage further study of the viral contribution to lung carcinogenesis.« less

Complementary use of optical coherence tomography and 5-aminolevulinic acid induced fluorescent spectroscopy for diagnosis of neoplastic processes in cervix and vulva

NASA Astrophysics Data System (ADS)

Sapozhnikova, Veronika V.; Shakhova, Natalia M.; Kamensky, Vladislav A.; Kuranov, Roman V.; Loshenov, Victor B.; Petrova, Svetlana A.

2003-07-01

A new approach to improving the diagnostic value of optical methods is suggested, which is based on a complementary investigation of different optical parameters of biotissues. The aim of this paper is comparative study of the feasibility of two optical methods - fluorescence spectroscopy and optical coherence tomography - for visualization of borders of neoplastic processes in the uterine cervix and vulva. Fluorescence spectroscopy is based on the detection of biochemical and optical coherence tomography on backscattering properties in norm and pathological changes of tissues. By means of these optical methods changes in biochemical and morphological properties of tissues were investigated. A parallel analysis of these two optical methods and histology from the center of tumors and their optical borders was made. Thirteen female patients with neoplastic changes in uterine cervix and vulva were enrolled in this study. The borders of the tumor determined by optical methods (fluorescence spectroscopy and optical coherence tomography) are coinciding with the biopsy proved ones. In addition, OCT and fluorescence borders of tumor in the uterine cervix and vulva exceeds colposcopically detectable borders, the averaging difference 2 mm. In future optical methods would considerably enhance diagnostic accuracy of conventional methods used in oncogynecology.

Capsule endoscopy in neoplastic diseases

PubMed Central

Pennazio, Marco; Rondonotti, Emanuele; de Franchis, Roberto

2008-01-01

Until recently, diagnosis and management of small-bowel tumors were delayed by the difficulty of access to the small bowel and the poor diagnostic capabilities of the available diagnostic techniques. An array of new methods has recently been developed, increasing the possibility of detecting these tumors at an earlier stage. Capsule endoscopy (CE) appears to be an ideal tool to recognize the presence of neoplastic lesions along this organ, since it is non-invasive and enables the entire small bowel to be visualized. High-quality images of the small-bowel mucosa may be captured and small and flat lesions recognized, without exposure to radiation. Recent studies on a large population of patients undergoing CE have reported small-bowel tumor frequency only slightly above that reported in previous surgical series (range, 1.6%-2.4%) and have also confirmed that the main clinical indication to CE in patients with small-bowel tumors is obscure gastrointestinal (GI) bleeding. The majority of tumors identified by CE are malignant; many were unsuspected and not found by other methods. However, it remains difficult to identify pathology and tumor type based on the lesion’s endoscopic appearance. Despite its limitations, CE provides crucial information leading in most cases to changes in subsequent patient management. Whether the use of CE in combination with other new diagnostic (MRI or multidetector CT enterography) and therapeutic (Push-and-pull enteroscopy) techniques will lead to earlier diagnosis and treatment of these neoplasms, ultimately resulting in a survival advantage and in cost savings, remains to be determined through carefully-designed studies. PMID:18785274

The use of neoplastic donors to increase the donor pool.

PubMed

Fiaschetti, P; Pretagostini, R; Stabile, D; Peritore, D; Oliveti, A; Gabbrielli, F; Cenci, S; Ricci, A; Vespasiano, F; Grigioni, W F

2012-09-01

The aim of the study was to evaluate the experience of the Centre-Sud Transplant Organization (OCST) area using cadaveric donor with neoplastic diseases to evaluate the possibility of transmission to recipients. From January 1, 2003, to December 31, 2010, the neoplastic risk has been reported to be 5.4% (377/4654 referred donors). In 2003, the number of donors with a tumor and their mean age were respectively: 60 (10.3%) and 59.6 ± 19.9; 2004: 33 (5.2%) and 61.4 ± 15.9; 2005: 32 (6%) and 62.8 ± 15.5; 2006: 46 (7%) and 60.7 ± 19.1; 2007: 51 (7%) and 58.9 ± 16; in 2008: 58 (7%) and 59.7 ± 19.6; 2009: 47 (7%) and 57 ± 26; 2010: 49 (7%) and 64 ± 16. The organ most affected by tumor has been the central nervous system (18%). The tumor was diagnosed before in 325 (86%) cases, versus during organ retrieval in 48 (12.7%) donor operations but before, which four cases (1%) occured after transplantation. According to the histological types and grades, 28 evaluated donors (8.2%) were suitable for transplantation. The histological types were: thyroid carcinoma (n = 3); prostate carcinoma (n = 8), renal clear cell carcinoma (n = 7), oncocytoma (n = 1), meningiomas (n = 2), dermofibrosarcoma (n = 1); verrucous carcinoma of the vulva (n = 1), colon adenocarcinoma (n = 1), grade II astrocytoma (n = 1), adrenal gland tumor (n = 1), gastric GIST (n = 1), oligodendroglioma (n = 1). Forty-five organs were retrieved (22 livers, 19 kidneys, 3 hearts, and 1 pancreas) and transplanted into 44 recipients with 1 liver-kidney combined transplantation. Four recipients died due to causes not related to the tumor. No donor-transmitted tumor was detected among the recipients. Donation is absolutely not indicated in cases of tumors with high metastatic potential and high grades. Performing an accurate evaluation of the donor, taking into account the histological grade, currently can allow, organ retrieval and transplantation with an acceptable risk. Copyright © 2012. Published by Elsevier

Depletion of HPV16 early genes induces autophagy and senescence in a cervical carcinogenesis model, regardless of viral physical state.

PubMed

Hanning, Jennifer E; Saini, Harpreet K; Murray, Matthew J; Caffarel, Maria M; van Dongen, Stijn; Ward, Dawn; Barker, Emily M; Scarpini, Cinzia G; Groves, Ian J; Stanley, Margaret A; Enright, Anton J; Pett, Mark R; Coleman, Nicholas

2013-11-01

In cervical carcinomas, high-risk human papillomavirus (HR-HPV) may be integrated into host chromosomes or remain extra-chromosomal (episomal). We used the W12 cervical keratinocyte model to investigate the effects of HPV16 early gene depletion on in vitro cervical carcinogenesis pathways, particularly effects shared by cells with episomal versus integrated HPV16 DNA. Importantly, we were able to study the specific cellular consequences of viral gene depletion by using short interfering RNAs known not to cause phenotypic or transcriptional off-target effects in keratinocytes. We found that while cervical neoplastic progression in vitro was characterized by dynamic changes in HPV16 transcript levels, viral early gene expression was required for cell survival at all stages of carcinogenesis, regardless of viral physical state, levels of early gene expression or histology in organotypic tissue culture. Moreover, HPV16 early gene depletion induced changes in host gene expression that were common to both episome-containing and integrant-containing cells. In particular, we observed up-regulation of autophagy genes, associated with enrichment of senescence and innate immune-response pathways, including the senescence-associated secretory phenotype (SASP). In keeping with these observations, HPV16 early gene depletion induced autophagy in both episome-containing and integrant-containing W12 cells, as evidenced by the appearance of autophagosomes, punctate expression of the autophagy marker LC3, conversion of LC3B-I to LC3B-II, and reduced levels of the autophagy substrate p62. Consistent with the reported association between autophagy and senescence pathways, HPV16 early gene depletion induced expression of the senescence marker beta-galactosidase and increased secretion of the SASP-related protein IGFBP3. Together, these data indicate that depleting HR-HPV early genes would be of potential therapeutic benefit in all cervical carcinogenesis pathways, regardless of viral

Neoplastic lesions in the nasal cavities of dogs.

PubMed

Spuzak, J; Jankowski, M; Kubiak, K; Glińska-Suchocka, K; Grzegory, M; Hałoń, A

2014-01-01

This paper aims at evaluating the frequency of nasal cavity tumors in dogs as well as comparing an endoscopic examination with a histopathological evaluation of the collected biopsy specimens. The study was conducted on 68 dogs. During the endoscopic examination, proliferative lesions were recognized in 20 dogs. During the histopathological examination, neoplastic lesions were confirmed in 95% of the dogs in which proliferative lesions were identified in the endoscopic examination. Adenocarcinoma occurred most frequently in the population under study.

Expression of a fms-related oncogene in carcinogen-induced neoplastic epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walker, C.; Nettesheim, P.; Barrett, J.C.

1987-04-01

Following carcinogen exposure in vitro, normal rat tracheal epithelial cells are transformed in a multistage process in which the cultured cells become immortal and ultimately, neoplastic. Five cell lines derived from tumors produced by neoplastically transformed rat tracheal epithelial cells were examined for the expression of 11 cellular oncogenes previously implicated in pulmonary or epithelial carcinogenesis. RNA homologous to fms was expressed at a level 5-19 times higher than normal tracheal epithelial cells in three of five of the tumor-derived lines. All three lines expressing high levels of fms-related RNA gave rise to invasive tumors of epithelial origin when injectedmore » into nude mice. Increased expression of the fms-related mRNA was not due to gene amplification, and no gene rearrangement was detected by Southern analyses. RNA blot analysis using a 3' v-fms probe detected a 9.5-kilobase message in the three tumor-derived lines, whereas both normal rat aveolar macrophages and the human choriocarcinoma line BeWo expressed a fms transcript of approx. = 4 kilobases. The authors conclude from these data that the gene expressed as a 9.5-kilobase transcript in these neoplastic epithelial cells is a member of a fms-related gene family but may be distinct from the gene that encodes the macrophage colony-stimulating factor (CSF-1) receptor.« less

[The effect of neoplastic disease and systemic disease of connective tissue on the occurrence of dehiscence laparotomy].

PubMed

Paunović, Milorad

2013-01-01

Dehiscence after laparotomy is one of the major complications of laparotomy. This is a partial or complete wound with disruption and evisceratio abdominal organs and require urgent reintervention. The aim of this study was to determine the impact of neoplastic disease and systemic disease of connective tissue on the occurrence of dehiscence laparotomy. A prospective study were included 612 patients operated at the Clinic for General Surgery in Nis in the period from January 2009 to December 2010. The effect of neoplastic disease and the presence of systemic disease of connective tissue on the occurrence of dehiscence laparotomy. Results are displayed numerically and in percentages. Of the total 24 patients with dehiscence laparotomy, 15 patients were male or 62.5% and 9 female patients, or 37.5%. There was a statistically significant association between dehiscence laparotomy and neoplastic diseases (c2 = 42,196; p < 0.01). There was no statistically significant association between dehiscence laparo-tomy and systemic disease of connective tissue (c2 = 0,028; p > 0.05). In patients with neoplastic diseases dehis-cence laparotomy is common, and in patients suffering from systemic disease of connective tissue dehiscence laparotomy occurs less frequently.

Can an endocytoscope system (ECS) predict histology in neoplastic lesions?

PubMed

Eberl, T; Jechart, G; Probst, A; Golczyk, M; Bittinger, M; Scheubel, R; Arnholdt, H; Knuechel, R; Messmann, H

2007-06-01

An endocytoscope system (ECS) has recently been developed with the possibility of super-high magnification of gastrointestinal mucosa, thus allowing in vivo imaging of living cells. The aim of the present study was to assess the potential of ECS in the prediction of histology in both normal gastrointestinal mucosa and neoplastic lesions. In total, 76 patients (57 men, 19 women; age range 37-86 years) with neoplastic lesions in the esophagus, stomach, or colon were enrolled into the study and underwent esophagogastroduodenoscopy or colonoscopy. After staining with 1% methylene blue, the mucosa was examined with the ECS probe (x 450 and x 1100 magnification), and video sequences were recorded on video disk. Biopsies from the examined areas were taken for histology and served as the gold standard. The endocytoscope video sequences were evaluated by two blinded pathologists. Finally the results were compared with those resulting from the evaluation of an experienced endoscopist who was aware of the macroscopic endoscopic pictures and the endocytoscope image results. A total of 25 patients with esophageal lesions, 28 patients with colonic lesions, and 23 patients with gastric lesions were examined. The sensitivity and specificity for the evaluation of the blinded pathologists was 81% and 100%, respectively, in the esophagus, 56% and 89% in the stomach, and 79% and 90% in the colon. If an endoscopist evaluated the endocytoscopic pictures in combination with the macroscopic endoscopic images sensitivity and specificity increased significantly. First experiences with ECS show good sensitivity rates even by blinded assessment for esophageal and colonic lesions. Sensitivity for neoplastic lesions in the stomach is lower because of gastric mucous secretion. Combining the endoscopic and cytoscopic appearance of the lesion may further enhance the diagnostic value of the method.

30 CFR 36.12 - Changes after certification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Changes after certification. 36.12 Section 36... TRANSPORTATION EQUIPMENT General Provisions § 36.12 Changes after certification. If an applicant desires to change any feature of certified equipment, he shall first obtain MSHA's approval of the change, pursuant...

Sodium hydroxide as a sclerosing agent in patients with neoplastic pleural effusion non-candidates for VATS: results of a minimally invasive protocol.

PubMed

Raices, Micaela; Czerwonko, Matías E; Dietrich, Agustin; Da Lozzo, Alejandro; Beveraggi, Enrique; Smith, David

2017-08-31

Symptomatic neoplastic pleural effusion (SNPE) is a significant cause of morbidity in patients with advanced neoplastic disease. These patients often present a deteriorated general condition which prevents them from undergoing pleurodesis with video-assisted thoracic surgery (VATS). We developed a minimally invasive therapeutic protocol specially designed for this population, achieved by combining chemical pleurodesis with placement of small-bore pleural catheters (PC), which resulted in early hospital discharge, low morbimortality and good therapeutic results. This study reports the safety and efficacy of administration of sodium hydroxide (NaOH) through PC in 60 patients diagnosed with SNPE who were admitted to Hospital Italiano de Buenos Aires between January 2012 and December 2015. Successful pleurodesis was achieved in 96% of procedures. Recurrence occurred in 25% of patients during follow-up, with recurrence occurring earlier than 30 days after pleurodesis in 8% of patients. There were no reports of major morbidity or associated mortality. In total, 44% of patients were discharged within 48 h of pleurodesis. Administration of NaOH through a small-bore PC represents an effective and safe method of pleurodesis in patients who are not candidates for talc pleurodesis by VATS.

Differentiation of nonneoplastic and neoplastic gallbladder polyps 1 cm or bigger with multi-detector row computed tomography.

PubMed

Park, Ko Woon; Kim, Seong Hyun; Choi, Seong Ho; Lee, Won Jae

2010-01-01

To evaluate useful computed tomographic features to differentiate nonneoplastic and neoplastic gallbladder polyps 1 cm or bigger. Thirty-one patients with 32 nonneoplastic polyps and 67 patients with 73 neoplastic polyps 1 cm or bigger underwent unenhanced and dual-phase (arterial and portal venous phases) multi-detector row computed tomography. Gallbladder polyps were diagnosed by cholecystectomy. Computed tomographic features including size (1.5 cm), surface (smooth or irregular), shape (pedunculated or sessile), accompanying wall thickening, basal indentation, perception on unenhanced images, and enhancement pattern between 2 groups were compared using univariate and multivariate analyses. On univariate analysis, age 55 years or older (P = 0.0019), size bigger than 1.5 cm (P < 0.0001), irregular surface (P = 0.0033), sessile shape (P = 0.0016), accompanying wall thickening (P = 0.0056), basal indentation (P = 0.0236), and perception on unenhanced images (P < 0.0001) were significantly more frequent in neoplastic polyps as compared with nonneoplastic polyps. On multivariate analysis, size bigger than 1.5 cm (P = 0.0260), sessile shape (P = 0.0397), and perception on unenhanced images (P < 0.0001) were statistically significant. Size bigger than 1.5 cm, sessile shape, and perception on unenhanced images are the main factors that differentiate neoplastic from nonneoplastic gallbladder polyps 1 cm or bigger.

30 CFR 35.12 - Changes after certification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Changes after certification. 35.12 Section 35..., AND APPROVAL OF MINING PRODUCTS FIRE-RESISTANT HYDRAULIC FLUIDS General Provisions § 35.12 Changes after certification. If an applicant desires to change any specification or characteristic of a...

Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using /sup 111/In-DTPA ventriculography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grossman, S.A.; Trump, D.L.; Chen, D.C.

1982-11-01

Cerebrospinal fluid flow dynamics were evaluated by /sup 111/In-diethylenetriamine pentaacetic acid (/sup 111/In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that /sup 111/In-DTPA cerebrospinal fluid flow imaging is useful in characterizingmore » these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis.« less

A Randomized Trial Comparing High Definition Colonoscopy Alone With High Definition Dye Spraying and Electronic Virtual Chromoendoscopy for Detection of Colonic Neoplastic Lesions During IBD Surveillance Colonoscopy.

PubMed

Iacucci, Marietta; Kaplan, Gilaad G; Panaccione, Remo; Akinola, Oluseyi; Lethebe, Brendan Cord; Lowerison, Mark; Leung, Yvette; Novak, Kerri L; Seow, Cynthia H; Urbanski, Stefan; Minoo, Parham; Gui, Xianyong; Ghosh, Subrata

2018-02-01

Dye spraying chromoendoscopy (DCE) is recommended for the detection of colonic neoplastic lesions in inflammatory bowel disease (IBD). The majority of neoplastic lesions are visible endoscopically and therefore targeted biopsies are appropriate for surveillance colonoscopy. To compare three different techniques for surveillance colonoscopy to detect colonic neoplastic lesions in IBD patients: high definition (HD), (DCE), or virtual chromoendoscopy (VCE) using iSCAN image enhanced colonoscopy. A randomized non-inferiority trial was conducted to determine the detection rates of neoplastic lesions in IBD patients with longstanding colitis. Patients with inactive disease were enrolled into three arms of the study. Endoscopic neoplastic lesions were classified by the Paris classification and Kudo pit pattern, then histologically classified by the Vienna classification. A total of 270 patients (55% men; age range 20-77 years, median age 49 years) were assessed by HD (n=90), VCE (n=90), or DCE (n=90). Neoplastic lesion detection rates in the VCE arm was non-inferior to the DCE arm. HD was non-inferior to either DCE or VCE for detection of all neoplastic lesions. In the lesions detected, location at right colon and the Kudo pit pattern were predictive of neoplastic lesions (OR 6.52 (1.98-22.5 and OR 21.50 (8.65-60.10), respectively). In this randomized trial, VCE or HD-WLE is not inferior to dye spraying colonoscopy for detection of colonic neoplastic lesions during surveillance colonoscopy. In fact, in this study HD-WLE alone was sufficient for detection of dysplasia, adenocarcinoma or all neoplastic lesions.

Impact of tissue type and content of neoplastic cells of samples on the quality of epidermal growth factor receptor mutation analysis among patients with lung adenocarcinoma

PubMed Central

PALIOGIANNIS, PANAGIOTIS; ATTENE, FEDERICO; COSSU, ANTONIO; DEFRAIA, EFISIO; PORCU, GIUSEPPE; CARTA, ANNAMARIA; SOTGIU, MARIA IGNAZIA; PAZZOLA, ANTONIO; CORDERO, LORENZO; CAPELLI, FRANCESCA; FADDA, GIOVANNI MARIA; ORTU, SALVATORE; SOTGIU, GIOVANNI; PALOMBA, GRAZIA; SINI, MARIA CRISTINA; PALMIERI, GIUSEPPE; COLOMBINO, MARIA

2015-01-01

Assessment of the epidermal growth factor receptor (EGFR) mutational status has become crucial in recent years in the molecular classification of patients with lung cancer. The impact of the type and quantity of malignant cells of the neoplastic specimen on the quality of mutation analysis remains to be elucidated, and only empirical and sporadic data are available. The aim of the present study was to investigate the impact of tissue type and content of neoplastic cells in the specimen on the quality of EGFR mutation analysis among patients with lung adenocarcinoma. A total of 515 patients with histologically-confirmed disease were included in the present study. Formalin-fixed paraffin embedded tissue samples were used for the mutation analysis and the content of the neoplastic cells was evaluated using light microscopy. Genomic DNA was isolated using a standard protocol. The coding sequences and splice junctions of exons 18, 19 and 21 in the EGFR gene were then screened for mutations by direct automated sequencing. The mean age of the patients examined was 64.9 years and 357 (69.3%) were male. A total of 429 tissue samples (83.3%) were obtained by biopsy and the remaining samples were obtained by surgery. A total of 456 samples (88.5%) were observed from primary lung adenocarcinomas, while 59 (11.5%) were from metastatic lesions. EGFR mutations occurred in 59 cases (11.5%); exon 18 mutations were detected in one case (1.7%), whereas exon 19 and 21 mutations were detected in 30 (51%) and 28 (47.3%) cases, respectively. EGFR mutations were more frequent in females and patients that had never smoked. The distribution of the mutations among primary and metastatic tissues exhibited no significant differences in the proportions of EGFR mutations detected. However, a statistically significant difference in the number of mutations detected was found between samples with at least 50% of neoplastic cells (450 cases-57 mutations; 12.7%) and those with <50% of neoplastic

Hexon modification to improve the activity of oncolytic adenovirus vectors against neoplastic and stromal cells in pancreatic cancer.

PubMed

Lucas, Tanja; Benihoud, Karim; Vigant, Frédéric; Schmidt, Christoph Q; Schmidt, Christoph Q Andreas; Wortmann, Andreas; Bachem, Max G; Simmet, Thomas; Kochanek, Stefan

2015-01-01

Primary pancreatic carcinoma has an unfavourable prognosis and standard treatment strategies mostly fail in advanced cases. Virotherapy might overcome this resistance to current treatment modalities. However, data from clinical studies with oncolytic viruses, including replicating adenoviral (Ad) vectors, have shown only limited activity against pancreatic cancer and other carcinomas. Since pancreatic carcinomas have a complex tumor architecture and frequently a strong stromal compartment consisting of non-neoplastic cell types (mainly pancreatic stellate cells = hPSCs) and extracellular matrix, it is not surprising that Ad vectors replicating in neoplastic cells will likely fail to eradicate this aggressive tumor type. Because the TGFβ receptor (TGFBR) is expressed on both neoplastic cells and hPSCs we inserted the TGFBR targeting peptide CKS17 into the hypervariable region 5 (HVR5) of the capsid protein hexon with the aim to generate a replicating Ad vector with improved activity in complex tumors. We demonstrated increased transduction of both pancreatic cancer cell lines and of hPSCs and enhanced cytotoxicity in co-cultures of both cell types. Surface plasmon resonance analysis demonstrated decreased binding of coagulation factor X to CKS17-modified Ad particles and in vivo biodistribution studies performed in mice indicated decreased transduction of hepatocytes. Thus, to increase activity of replicating Ad vectors we propose to relax tumor cell selectivity by genetic hexon-mediated targeting to the TGFBR (or other receptors present on both neoplastic and non-neoplastic cells within the tumor) to enable replication also in the stromal cell compartment of tumors, while abolishing hepatocyte transduction, and thereby increasing safety.

Promotional effects of CO2 laser on neoplastic lesions in hamsters

NASA Astrophysics Data System (ADS)

Kingsbury, Jeffrey S.; Margarone, Joseph E., III; Satchidanand, S.; Liebow, Charles

1991-06-01

Surgical incision may have promotional effects on neoplastic lesions, possibly through release of tissue growth factors (e.g., EGF, FGF(beta) , IGF, TGF(alpha) ). The CO2 laser may precipitate altered release of these factors. To test this, .5 cm laser, and scalpel incisions were made into fields treated by application of .5% DMBA in acetone, 3 times a week for 6 weeks (group 1) and 12 weeks (group 2). DMBA is a complete carcinogen (initiator and promoter). At 6 weeks, chemically, but not histologically, definable premalignant lesions are seen. Treatment for 12 weeks causes histologic neoplasia which can be graded with T-N-M classification. For both groups, the surgical sites were examined clinically and histologically 4 weeks post-op in a blind fashion. Standard criteria were utilized for defining neoplasia. For group 1, 3 out of 6 laser treated animals developed large exophytic squamous cell carcinomas, but no lesions developed in 12 contralateral, 3 control and 3 scalpel treated pouches. For group 2, 12 of 16 laser treated animals developed tumor with mean grade of 1.75 and mean size of 7.4 mm, 5 of 6 scalpel treated animals developed tumor with mean grade of 1.83 and mean size of 3.6 mm and 3 of 6 control animals developed tumor with mean grade of 1.00 and mean size of 1.5 mm. By the Student 't' test on the binomial distribution lasers cause significant promotion (p < .01). These results suggest that laser surgery may have earlier and more profound promotional effects than scalpel on initiated cells relative to tumor size in the vicinity of the wound site by increased release of growth factors.

Changing Faces: The Early Childhood Profession in Australia.

ERIC Educational Resources Information Center

Lambert, Beverley, Ed.

This collection of 14 essays addresses the changes and challenges that the early childhood education profession in Australia has faced in recent years, and covers a wide range of important issues of particular relevance to the preparation of early childhood professionals. The essays are: (1) "The Changing Ecology of Australian Childhood"…

Neoplastic Fever: All who Shiver are not Infected.

PubMed

Sharma, Yogesh B; More, Aparna Vishal

2017-03-01

We report the case of previously healthy 14 years old male who presented high grade fever and headache. There was a history of convulsion at age of 7 years, so MRI Brain was done. It was suggestive of a central nervous system neoplasm. Our patient had only two days of fever which is an unusual presentation of a neoplasm. The paper should be of interest to the clinicians as neoplastic fever as cause of acute febrile illness is considered as a remote possibility. © Journal of the Association of Physicians of India 2011.

34 CFR 604.12 - Changes in the agreement.

Code of Federal Regulations, 2010 CFR

2010-07-01

... organizational or personnel changes are not subject to prior modification of the agreement, but information... 34 Education 3 2010-07-01 2010-07-01 false Changes in the agreement. 604.12 Section 604.12... Agreements § 604.12 Changes in the agreement. (a) The agreement shall remain in effect until substantial...

Changes in insomnia subtypes in early Parkinson disease.

PubMed

Tholfsen, Lena K; Larsen, Jan P; Schulz, Jörn; Tysnes, Ole-Bjørn; Gjerstad, Michaela D

2017-01-24

To examine the development of factors associated with insomnia in a cohort of originally drug-naive patients with incident Parkinson disease (PD) during the first 5 years after diagnosis. One hundred eighty-two drug-naive patients with PD derived from a population-based incident cohort and 202 control participants were assessed for insomnia before treatment initiation and were repeatedly examined after 1, 3, and 5 years. Insomnia was diagnosed according to the Stavanger Sleepiness Questionnaire. The Parkinson's Disease Sleep Scale was used to differentiate sleep initiation problems from problems of sleep maintenance. Generalized estimating equation models were applied for statistical measures. The prevalence of insomnia in general was not higher in patients with PD compared to controls at the 5-year follow-up. There were changes in the prevalence of the different insomnia subtypes over the 5-year follow-up. The prevalence of solitary problems in sleep maintenance increased from 31% (n = 18) in the drug-naive patients at baseline to 49% (n = 29) after 1 year and were associated with the use of dopamine agonists and higher Montgomery-Åsberg Depression Rating Scale scores. The prevalence of solitary sleep initiation problems decreased continuously from 21% (n = 12) at baseline to 7.4% (n = 4) after 5 years; these were associated with less daytime sleepiness. The prevalence rates of the different insomnia subtypes changed notably in patients with early PD. The frequency of sleep maintenance problems increased, and these problems were associated with dopamine agonist use and depressive symptoms, while the total number of patients with insomnia remained stable. Our findings reflect the need for early individual assessments of insomnia subtypes and raise the possibility of intervention to reduce these symptoms in patients with early PD. © 2016 American Academy of Neurology.

Gene expression profiling reveals underlying molecular mechanisms of the early stages of tamoxifen-induced rat hepatocarcinogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pogribny, Igor P.; Bagnyukova, Tetyana V.; Tryndyak, Volodymyr P.

2007-11-15

Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce non-alcoholic steatohepatitis, which is a life-threatening fatty liver disease with a risk of progression to cirrhosis and hepatocellular carcinoma. In recent years, the high-throughput microarray technology for large-scale analysis of gene expression has become a powerful tool for increasing the understanding of the molecular mechanisms of carcinogenesis and for identifying new biomarkers with diagnostic and predictive values. Inmore » the present study, we used the high-throughput microarray technology to determine the gene expression profiles in the liver during early stages of tamoxifen-induced rat hepatocarcinogenesis. Female Fisher 344 rats were fed a 420 ppm tamoxifen containing diet for 12 or 24 weeks, and gene expression profiles were determined in liver of control and tamoxifen-exposed rats. The results indicate that early stages of tamoxifen-induced liver carcinogenesis are characterized by alterations in several major cellular pathways, specifically those involved in the tamoxifen metabolism, lipid metabolism, cell cycle signaling, and apoptosis/cell proliferation control. One of the most prominent changes during early stages of tamoxifen-induced hepatocarcinogenesis is dysregulation of signaling pathways in cell cycle progression from the G{sub 1} to S phase, evidenced by the progressive and sustained increase in expression of the Pdgfc, Calb3, Ets1, and Ccnd1 genes accompanied by the elevated level of the PI3K, p-PI3K, Akt1/2, Akt3, and cyclin B, D1, and D3 proteins. The early appearance of these alterations suggests their importance in the mechanism of neoplastic cell transformation induced by tamoxifen.« less

Neoplastic sigmoid-uterine fistula. An exceptional complication of large intestine cancer

PubMed Central

ZANGHÌ, G.; LEANZA, V.; VECCHIO, R.; D’AGATI, A.; CORDOVA, S.; RINZIVILLO, N.M.; LODATO, M.; LEANZA, G.

2017-01-01

Neoplastic sigmoid-uterine fistula is an extremely rare condition because the uterus is a thick and muscular organ. A 74-year-old woman was admitted to the First Aid Station suffering from abdominal pain and foul smelling vaginal discharge. Gynaecological examination showed fecal drainage from the cervical orifice, while the uterus was regular in size but very firm and painful. Ovaries and fallopian tubes were not palpable owing to abdominal tenderness. Ultrasounds reveled inhomogeneous thickening of uterine cavity, without detecting fistula. Contrast Medium CT (CMCT) showed Douglas’ recto-uterine pouch occluded. The sigmoid wall was very thin exception a site where a fistula was suspected. At the surgery severe adhesions of the sigma-rectum with the posterior uterine wall were observed. After adhesiolysis, 18 cm colon-sigma-rectum was removed. Total hysterectomy with salpingooophorectomy was performed. Lymphadenectomy ended the procedure. Anatomical specimen confirmed sigmoid-uterine fistula. At histology a mildly differentiated adenocarcinoma of sigma-rectum was shown. Postoperative course was uneventful. Such a case of neoplastic sigmoid-uterine fistula has not been reported so far. PMID:28460202

[Value of narrow band imaging endoscopy in detection of early laryngeal squamous cell carcinoma].

PubMed

Staníková, L; Kučová, H; Walderová, R; Zeleník, K; Šatanková, J; Komínek, P

2015-01-01

Narrow band imaging (NBI) is an endoscopic method using filtered wavelengths in detection of microvascular abnormalities associated with preneoplastic and neoplastic changes of the mucosa. The aim of the study is to evaluate the value of NBI endoscopy in the dia-gnosis of laryngeal precancerous and early stages of cancerous lesions and to investigate impact of NBI method in prehistological diagnostics in vivo. One hundred patients were enrolled in the study and their larynx was investigated using white light HD endoscopy and narrow band imaging between 6/ 2013- 10/ 2014. Indication criteria included chronic laryngitis, hoarseness for more than three weeks or macroscopic laryngeal lesion. Features of mucosal lesions were evaluated by white light endoscopy and afterwards were compared with intra-epithelial papillary capillary loop changes, viewed using NBI endoscopy. Suspicious lesions (leukoplakia, exophytic tumors, recurrent respiratory papillomatosis and/ or malignant type of vascular network by NBI endoscopy) were evaluated by histological analysis, results were compared with prehistological NBI dia-gnosis. Using NBI endoscopy, larger demarcation of pathological mucosal features than in white light visualization were recorded in 32/ 100 (32.0%) lesions, in 4/ 100 (4.0%) cases even new lesions were detected only by NBI endoscopy. 63/ 100 (63.0%) suspected lesions were evaluated histologically -  malign changes (carcinoma in situ or invasive carcinoma) were observed in 25/ 63 (39.7%). Prehistological diagnostics of malignant lesions using NBI endoscopy were in agreement with results of histological examination in 23/ 25 (92.0%) cases. The sensitivity of NBI in detecting malignant lesions was 89.3%, specificity of this method was 94.9%. NBI endoscopy is a promising optical technique enabling in vivo differentiation of superficial neoplastic lesions. These results suggest endoscopic NBI may be useful in the early detection of laryngeal cancer and precancerous

Genetic biomarkers for neoplastic colorectal cancer in peripheral lymphocytes.

PubMed

Ionescu, Mirela; Ciocirlan, Mihai; Ionescu, Cristina; Becheanu, Gabriel; Gologan, Serban; Teiusanu, Adriana; Arbanas, Tudor; Mircea, Diculescu

2011-04-01

Loss of genomic stability appears as a key step in colorectal carcinogenesis. Micronucleus (MN) designates a chromosome fragment or an entire chromosme which lags behind mitosis. MN may be noticed as an additional nucleus within the cytoplasm cell during the intermediate mitosis phases. We tested the hypothesis that MN and its related anomalies may be associated with the presence of neoplastic colorectal lesions. Peripheral blood lymphocytes were cultured and microscopically examined. The frequency of micronuclei (FMN) and the presence of nucleoplasmic bridges (NPB) in binucleated cells were compared in patients with of without colorectal neoplastic lesions. We included 45 patients undergoing colonoscopy, 23 males and 22 females, with a median age of 59. 17 patients had polyps, 11 colorectal cancer (CRC) and 17 had a normal colonoscopy. The FMN was significantly higher in women than in men (8.14 vs 4.17, p=0.008); NPB were significantly less frequent in patients with advanced adenomas (>10mm or vilous) or CRC (p=0.044) when compared with patients with normal colonoscopy, hiperplastic polyps or non-advanced adenomas. Micronuclei are more frequent in women, but its frequency was not significantly different in patients with advanced adenomas or CRC. Null or low frequency values for nucleoplasmic bridges presence in peripheral lymphocyte may be predictive for advanced adenomas and colorectal cancer.

Genetic Biomarkers for Neoplastic Colorectal Cancer in Peripheral Lymphocytes

PubMed Central

Ionescu, Mirela; Ciocirlan, Mihai; Ionescu, Cristina; Becheanu, Gabriel; Gologan, Serban; Teiusanu, Adriana; Arbanas, Tudor; Mircea, Diculescu

2011-01-01

ABSTRACT Background: Loss of genomic stability appears as a key step in colorectal carcinogenesis. Micronucleus (MN) designates a chromosome fragment or an entire chromosme which lags behind mitosis. MN may be noticed as an additional nucleus within the cytoplasm cell during the intermediate mitosis phases. We tested the hypothesis that MN and its related anomalies may be associated with the presence of neoplastic colorectal lesions. Method: Peripheral blood lymphocytes were cultured and microscopically examined. The frequency of micronuclei (FMN) and the presence of nucleoplasmic bridges (NPB) in binucleated cells were compared in patients with of without colorectal neoplastic lesions. Results: We included 45 patients undergoing colonoscopy, 23 males and 22 females, with a median age of 59. 17 patients had polyps, 11 colorectal cancer (CRC) and 17 had a normal colonoscopy. The FMN was significantly higher in women than in men (8.14 vs 4.17, p=0.008); NPB were significantly less frequent in patients with advanced adenomas (>10mm or vilous) or CRC (p=0.044) when compared with patients with normal colonoscopy, hiperplastic polyps or non-advanced adenomas. Conclusion: Micronuclei are more frequent in women, but its frequency was not significantly different in patients with advanced adenomas or CRC. Null or low frequency values for nucleoplasmic bridges presence in peripheral lymphocyte may be predictive for advanced adenomas and colorectal cancer. PMID:22205889

Assessing early communication skills at 12 months: a retrospective study of Autism Spectrum Disorder.

PubMed

Swain, Nathaniel Robert; Eadie, Patricia Ann; Prior, Margot Ruth; Reilly, Sheena

2015-07-01

Early identification of Autism Spectrum Disorder (ASD) is currently limited by the absence of reliable biological markers for the disorder, as well as the reliability of screening and assessment tools for children aged between 6 and 18 months. Ongoing research has demonstrated the importance of early social communication skills in differentiating children later diagnosed with ASD from their typically developing (TD) peers, but researchers have not yet investigated whether these differences can be detected using community-ascertained systematic observation data as early as 12 months. To investigate whether differences in early social communication skills can be detected at 12 months of age, comparing children later diagnosed with ASD, and TD peers; and to determine whether differences remain when groupings are based on age of subsequent ASD diagnosis. From a prospective community-ascertained sample, we collected data on children in early life, then conducted retrospective analyses for those children who were later diagnosed with ASD by the age of 7 years, compared with matched TD peers. We analysed standardized observational data of early communication skills, collected using the Communication and Symbolic Behavior Scales-Developmental Profile (CSBS-DP) Behavior Sample, when participants were 12 months of age. Children in the ASD group exhibited significantly lower social communication skills than the TD group, including on the Total score and Social and Symbolic Composite scores of the CSBS-DP Behavior Sample. Differences on the Total score and Social Composite were also detected for both early and late ASD diagnosis groups when compared with the TD group. These findings give further support for the importance of social communication in assessing children at risk of ASD as early as 12 months of age. Future research could evaluate the sensitivity and specificity of direct observation of these early communication skills as diagnostic indicators for ASD at 12 months

Differential diagnosis of well-differentiated squamous cell carcinoma from non-neoplastic oral mucosal lesions: New cytopathologic evaluation method dependent on keratinization-related parameters but not nuclear atypism.

PubMed

Hara, Hitoshi; Misawa, Tsuneo; Ishii, Eri; Nakagawa, Miki; Koshiishi, Saki; Amemiya, Kenji; Oyama, Toshio; Tominaga, Kazuya; Cheng, Jun; Tanaka, Akio; Saku, Takashi

2017-05-01

The cytology of oral squamous cell carcinoma (SCC) is challenging because oral SCC cells tend to be well differentiated and lack nuclear atypia, often resulting in a false negative diagnosis. The purpose of this study was to establish practical cytological parameters specific to oral SCCs. We reviewed 123 cases of malignancy and 53 of non-neoplastic lesions of the oral mucosa, which had been diagnosed using both cytology and histopathology specimens. From those, we selected 12 SCC and 4 CIS cases that had initially been categorized as NILM to ASC-H with the Bethesda system, as well as 4 non-neoplastic samples categorized as LSIL or ASC-H as controls, and compared their characteristic findings. After careful examinations, we highlighted five cytological parameters, as described in Results. Those 20 cytology samples were then reevaluated by 4 independent examiners using the Bethesda system as well as the 5 parameters. Five cytological features, (i) concentric arrangement of orangeophilic cells (indicating keratin pearls), (ii) large number of orangeophilic cells, (iii) bizarre-shaped orangeophilic cells without nuclear atypia, (iv) keratoglobules, and (v) uneven filamentous cytoplasm, were found to be significant parameters. All malignant cases contained at least one of those parameters, while none were observed in the four non-neoplastic cases with nuclear atypia. In reevaluations, the Bethesda system did not help the screeners distinguish oral SCCs from non-neoplastic lesions, while use of the five parameters enabled them to make a diagnosis of SCC. Recognition of the present five parameters is useful for oral SCC cytology. Diagn. Cytopathol. 2017;45:406-417. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Serum big endothelin-1 as a clinical marker for cardiopulmonary and neoplastic diseases in dogs.

PubMed

Fukumoto, Shinya; Hanazono, Kiwamu; Miyasho, Taku; Endo, Yoshifumi; Kadosawa, Tsuyoshi; Iwano, Hidetomo; Uchide, Tsuyoshi

2014-11-24

Many studies of human subjects have demonstrated the utility of assessing serum levels of endothelin-1 (ET-1) and big ET-1 as clinical biomarkers in cardiopulmonary and neoplastic diseases. In this study we explored the feasibility of using serum big ET-1 as a reliable veterinary marker in dogs with various cardiopulmonary and neoplastic diseases. Serum big ET-1 levels were measured by ELISA in dogs with cardiopulmonary (n=21) and neoplastic diseases (n=57). Dogs exhibiting cardiopulmonary disease were divided into two groups based on the velocity of tricuspid valve regurgitation (3.0>m/s) measured by ultrasound: without and with pulmonary hypertension. Big ET-1 levels for the dogs with the diseases were compared with levels in normal healthy dogs (n=17). Dogs with cardiopulmonary disease (4.6±4.6 pmol/l) showed a significantly (P<0.01) higher level of big ET-1 than healthy control dogs (1.1±0.53 pmol/l). Serum levels in the dogs with pulmonary hypertension (6.2±5.3 pmol/l) were significantly (P<0.01) higher than those without pulmonary hypertension (2.0±0.6 pmol/l). Dogs with hemangiosarcoma (5.6±2.2 pmol/l), adenocarcinoma (2.0±1.8 pmol/l), histiocytic sarcoma (3.3±1.9 pmol/l), chondrosarcoma or osteosarcoma (3.0±1.6 pmol/l) and hepatocellular carcinoma (2.7±1.8 pmol/l) showed significantly (P<0.05) higher levels than healthy control dogs. These findings point to the potential of serum big ET-1 as a clinical marker for cardiopulmonary and neoplastic diseases in dogs. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

An in vitro model demonstrates the potential of neoplastic human germ cells to influence the tumour microenvironment.

PubMed

Klein, B; Schuppe, H-C; Bergmann, M; Hedger, M P; Loveland, B E; Loveland, K L

2017-07-01

Testicular germ cell tumours (TGCT) typically contain high numbers of infiltrating immune cells, yet the functional nature and consequences of interactions between GCNIS (germ cell neoplasia in situ) or seminoma cells and immune cells remain unknown. A co-culture model using the seminoma-derived TCam-2 cell line and peripheral blood mononuclear cells (PBMC, n = 7 healthy donors) was established to investigate how tumour and immune cells each contribute to the cytokine microenvironment associated with TGCT. Three different co-culture approaches were employed: direct contact during culture to simulate in situ cellular interactions occurring within seminomas (n = 9); indirect contact using well inserts to mimic GCNIS, in which a basement membrane separates the neoplastic germ cells and immune cells (n = 3); and PBMC stimulation prior to direct contact during culture to overcome the potential lack of immune cell activation (n = 3). Transcript levels for key cytokines in PBMC and TCam-2 cell fractions were determined using RT-qPCR. TCam-2 cell fractions showed an immediate increase (within 24 h) in several cytokine mRNAs after direct contact with PBMC, whereas immune cell fractions did not. The high levels of interleukin-6 (IL6) mRNA and protein associated with TCam-2 cells implicate this cytokine as important to seminoma physiology. Use of PBMCs from different donors revealed a robust, repeatable pattern of changes in TCam-2 and PBMC cytokine mRNAs, independent of potential inter-donor variation in immune cell responsiveness. This in vitro model recapitulated previous data from clinical TGCT biopsies, revealing similar cytokine expression profiles and indicating its suitability for exploring the in vivo circumstances of TGCT. Despite the limitations of using a cell line to mimic in vivo events, these results indicate how neoplastic germ cells can directly shape the surrounding tumour microenvironment, including by influencing local immune responses. IL6

THE NEOPLASTIC POTENTIALITIES OF MOUSE EMBRYO TISSUES

PubMed Central

Smith, William E.

1950-01-01

The lung tissue of mouse embryos of the C strain proliferates to some extent after implantation in adult hosts of the same breed and rapidly differentiates, forming a parenchyma remarkably like the normal. The grafts persist long. When methylcholanthrene dissolved in olive oil has been introduced with them much more growth of them occurs. The carcinogen induces a pronounced metaplasia of the epithelium of the bronchial tree, and the altered cells are often aggressive, multiplying, invading, and largely replacing the parenchyma about them. So closely do they resemble malignant elements in aspect and behavior that it is frequently difficult to tell whether carcinomatous change is not actually present. Genuine tumors soon arise, multiple benign adenomas sometimes appearing within 3 weeks, and indubitable carcinomas a few weeks later. Not a few of the cancers are of transitional cell type, that is to say are expressive of an intermediate stage in the metaplasia. Under the influence of methylcholanthrene the cells lining the alveolar spaces of the graft sometimes undergo metaplasia also, with result in stratified squamous epithelium. It follows that there is reason to doubt the current assumption that all squamous cell carcinomas of the lung necessarily arise from the bronchial tree. The findings, taken with others previously reported, make it difficult to suppose, furthermore, that the generality of lung tumors can be due to neoplastic viruses entering the organism in postnatal life and having no broader scope than those thus far discovered. PMID:15395575

GhNAC12, a neutral candidate gene, leads to early aging in cotton (Gossypium hirsutum L).

PubMed

Zhao, Fengli; Ma, Jianhui; Li, Libei; Fan, Shuli; Guo, Yaning; Song, Meizhen; Wei, Hengling; Pang, Chaoyou; Yu, Shuxun

2016-01-15

NAC (NAM, ATAF, and CUC) is one of the largest transcription factor families in plants, and its members play various roles in plant growth, development, and the response to biotic and abiotic stresses. Currently, 77 NAC genes have been reported in cotton (Gossypium hirsutum L.). And GhNAC12 showed up-regulation during leaf senescence, but its role in this process is poorly understood. In the present study, a preliminary function analysis of GhNAC12 was performed during leaf senescence. qRT-PCR analysis indicated that GhNAC12 expression increased during the early-aging process and the aging of cotyledons. Additionally, we observed that overexpression of GhNAC12 in Arabidopsis led to early senescence (early aging). Our findings suggest that GhNAC12 is a candidate gene for early aging in upland cotton cultivars. Neutrality tests suggested that there was no selection pressure imposed on GhNAC12 during the domestication of upland cotton. Copyright © 2015 Elsevier B.V. All rights reserved.

M-COPA suppresses endolysosomal Kit-Akt oncogenic signalling through inhibiting the secretory pathway in neoplastic mast cells.

PubMed

Hara, Yasushi; Obata, Yuuki; Horikawa, Keita; Tasaki, Yasutaka; Suzuki, Kyohei; Murata, Takatsugu; Shiina, Isamu; Abe, Ryo

2017-01-01

Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs), acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib. Recently, we showed that in neoplastic mast cells that endogenously express an imatinib-resistant Kit mutant, Kit causes oncogenic activation of the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway and the signal transducer and activator of transcription 5 (STAT5) but only on endolysosomes and on the endoplasmic reticulum (ER), respectively. Here, we show a strategy for inhibition of the Kit-PI3K-Akt pathway in neoplastic mast cells by M-COPA (2-methylcoprophilinamide), an inhibitor of this secretory pathway. In M-COPA-treated cells, Kit localization in the ER is significantly increased, whereas endolysosomal Kit disappears, indicating that M-COPA blocks the biosynthetic transport of Kit from the ER. The drug greatly inhibits oncogenic Akt activation without affecting the association of Kit with PI3K, indicating that ER-localized Kit-PI3K complex is unable to activate Akt. Importantly, M-COPA but not imatinib suppresses neoplastic mast cell proliferation through inhibiting anti-apoptotic Akt activation. Results of our M-COPA treatment assay show that Kit can activate Erk not only on the ER but also on other compartments. Furthermore, Tyr568/570, Tyr703, Tyr721, and Tyr936 in Kit are phosphorylated on the ER, indicating that these five tyrosine residues are all phosphorylated before mutant Kit reaches the plasma membrane (PM). Our study provides evidence that Kit is tyrosine-phosphorylated soon after synthesis on the ER but is unable to

M-COPA suppresses endolysosomal Kit-Akt oncogenic signalling through inhibiting the secretory pathway in neoplastic mast cells

PubMed Central

Hara, Yasushi; Obata, Yuuki; Horikawa, Keita; Tasaki, Yasutaka; Suzuki, Kyohei; Murata, Takatsugu; Shiina, Isamu; Abe, Ryo

2017-01-01

Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs), acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib. Recently, we showed that in neoplastic mast cells that endogenously express an imatinib-resistant Kit mutant, Kit causes oncogenic activation of the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway and the signal transducer and activator of transcription 5 (STAT5) but only on endolysosomes and on the endoplasmic reticulum (ER), respectively. Here, we show a strategy for inhibition of the Kit-PI3K-Akt pathway in neoplastic mast cells by M-COPA (2-methylcoprophilinamide), an inhibitor of this secretory pathway. In M-COPA-treated cells, Kit localization in the ER is significantly increased, whereas endolysosomal Kit disappears, indicating that M-COPA blocks the biosynthetic transport of Kit from the ER. The drug greatly inhibits oncogenic Akt activation without affecting the association of Kit with PI3K, indicating that ER-localized Kit-PI3K complex is unable to activate Akt. Importantly, M-COPA but not imatinib suppresses neoplastic mast cell proliferation through inhibiting anti-apoptotic Akt activation. Results of our M-COPA treatment assay show that Kit can activate Erk not only on the ER but also on other compartments. Furthermore, Tyr568/570, Tyr703, Tyr721, and Tyr936 in Kit are phosphorylated on the ER, indicating that these five tyrosine residues are all phosphorylated before mutant Kit reaches the plasma membrane (PM). Our study provides evidence that Kit is tyrosine-phosphorylated soon after synthesis on the ER but is unable to

Early behavioral changes and quantitative analysis of neuropathological features in murine prion disease

PubMed Central

Borner, Roseane; Bento-Torres, João; Souza, Diego RV; Sadala, Danyelle B; Trevia, Nonata; Farias, José Augusto; Lins, Nara; Passos, Aline; Quintairos, Amanda; Diniz, José Antônio; Perry, Victor Hugh; Vasconcelos, Pedro Fernando; Cunningham, Colm

2011-01-01

Behavioral and neuropathological changes have been widely investigated in murine prion disease but stereological based unbiased estimates of key neuropathological features have not been carried out. After injections of ME7 infected (ME7) or normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6, we assessed behavioral changes on hippocampal-dependent tasks. We also estimated by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total number of neurons, reactive astrocytes, activated microglia and perineuronal nets (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino Swiss mice. On average, early behavioral changes in albino Swiss mice start four weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data in albino Swiss mice revealed that four of nine subjects start to change their behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal degeneration and stereological data showed that early astrocytosis, microgliosis and reduction in the perineuronal nets are independent of a change in the number of neuronal cell bodies. Statistical analysis revealed that the septal region had greater levels of neuroinflammation and extracellular matrix damage than CA1. This stereological and multivariate analysis at early stages of disease in an outbred model of prion disease provided new insights connecting behavioral changes and neuroinflammation and seems to be important to understand the mechanisms of prion disease progression. PMID:21862877

Nuclear Division Index may Predict Neoplastic Colorectal Lesions.

PubMed

Ionescu, Mirela E; Ciocirlan, Mihai; Becheanu, Gabriel; Nicolaie, Tudor; Ditescu, Cristina; Teiusanu, Adriana G; Gologan, Serban I; Arbanas, Tudor; Diculescu, Mircea M

2011-07-01

Colorectal cancer (CRC) develops by accumulation of multiple genetic damages leading to genetic instability that can be evaluated by cytogenetic methods. In the current study we used Cytokinesis-Blocked Micronucleus Assay (CBMN) technique to assess the behavior of Nuclear Division Index(NDI) in peripheral lymphocytes of patients with CRC and polyps versus patients with normal colonoscopy. Blood samples were collected from patients after informed consent. By CBMN technique we assessed the proportion of mono-nucleated, bi-nucleated, tri-nucleated and tetra-nucleated cells/500 cells, to calculate NDI. Data were statistically analyzed using the SPSS 11.0 package. 45 patients were available for analysis, 23 men and 22 women, with a mean age of 58.7±13.5. 17 had normal colonoscopy, 17 colonic polyps and 11 CRC. The mean NDI values were significantly smaller for patients with CRC or polyps than in patients with normal colonoscopy (1.57 vs 1.73, p=0.013). The difference persisted for patients with neoplastic lesions (adenomas and carcinomas) when compared with patients with normal colonoscopy or non neoplastic (hyperplastic) polyps (1.56 vs.1.71, p=0.018). The NDI cut-off value to predict the presence of adenomas or carcinomas was equal to 1.55 with a 54.2% sensitivity and 81% specificity of lower values (p=0.019). The NDI cut off value to predict the presence of advanced adenomas or cancer was 1.525 for a sensitivity of 56.3% and a specificity of 82.8% (p=0.048). NDI may be useful in screening strategies for colorectal cancer as simple, noninvasive, inexpensive cytogenetic biomarker.

Nuclear Division Index may Predict Neoplastic Colorectal Lesions

PubMed Central

IONESCU, Mirela E.; CIOCIRLAN, Mihai; BECHEANU, Gabriel; NICOLAIE, Tudor; DITESCU, Cristina; TEIUSANU, Adriana G.; GOLOGAN, Serban I.; ARBANAS, Tudor; DICULESCU, Mircea M.

2011-01-01

ABSTRACT Background: Colorectal cancer (CRC) develops by accumulation of multiple genetic damages leading to genetic instability that can be evaluated by cytogenetic methods. In the current study we used Cytokinesis-Blocked Micronucleus Assay (CBMN) technique to assess the behavior of Nuclear Division Index(NDI) in peripheral lymphocytes of patients with CRC and polyps versus patients with normal colonoscopy. Methods: Blood samples were collected from patients after informed consent. By CBMN technique we assessed the proportion of mono-nucleated, bi-nucleated, tri-nucleated and tetra-nucleated cells/500 cells, to calculate NDI. Data were statistically analyzed using the SPSS 11.0 package. Results: 45 patients were available for analysis, 23 men and 22 women, with a mean age of 58.7±13.5. 17 had normal colonoscopy, 17 colonic polyps and 11 CRC. The mean NDI values were significantly smaller for patients with CRC or polyps than in patients with normal colonoscopy (1.57 vs 1.73, p=0.013). The difference persisted for patients with neoplastic lesions (adenomas and carcinomas) when compared with patients with normal colonoscopy or non neoplastic (hyperplastic) polyps (1.56 vs.1.71, p=0.018). The NDI cut-off value to predict the presence of adenomas or carcinomas was equal to 1.55 with a 54.2% sensitivity and 81% specificity of lower values (p=0.019). The NDI cut off value to predict the presence of advanced adenomas or cancer was 1.525 for a sensitivity of 56.3% and a specificity of 82.8% (p=0.048). Conclusion: NDI may be useful in screening strategies for colorectal cancer as simple, noninvasive, inexpensive cytogenetic biomarker. PMID:22368693

Temporal dissection of K-ras(G12D) mutant in vitro and in vivo using a regulatable K-ras(G12D) mouse allele.

PubMed

Wang, Zuoyun; Feng, Yan; Bardeesy, Nabeel; Bardessy, Nabeel; Wong, Kwok-Kin; Liu, Xin-Yuan; Ji, Hongbin

2012-01-01

Animal models which allow the temporal regulation of gene activities are valuable for dissecting gene function in tumorigenesis. Here we have constructed a conditional inducible estrogen receptor-K-ras(G12D) (ER-K-ras(G12D)) knock-in mice allele that allows us to temporally switch on or off the activity of K-ras oncogenic mutant through tamoxifen administration. In vitro studies using mice embryonic fibroblast (MEF) showed that a dose of tamoxifen at 0.05 µM works optimally for activation of ER-K-ras(G12D) independent of the gender status. Furthermore, tamoxifen-inducible activation of K-ras(G12D) promotes cell proliferation, anchor-independent growth, transformation as well as invasion, potentially via activation of downstream MAPK pathway and cell cycle progression. Continuous activation of K-ras(G12D) in vivo by tamoxifen treatment is sufficient to drive the neoplastic transformation of normal lung epithelial cells in mice. Tamoxifen withdrawal after the tumor formation results in apoptosis and tumor regression in mouse lungs. Taken together, these data have convincingly demonstrated that K-ras mutant is essential for neoplastic transformation and this animal model may provide an ideal platform for further detailed characterization of the role of K-ras oncogenic mutant during different stages of lung tumorigenesis.

Physical status of the E2 human papilloma virus 16 viral gene in cervical preneoplastic and neoplastic lesions.

PubMed

Tonon, S A; Picconi, M A; Bos, P D; Zinovich, J B; Galuppo, J; Alonio, L V; Teyssie, A R

2001-05-01

Integration of human papilloma virus (HPV) 16 DNA is considered an important genetic change in cervical lesion progression towards ICC. The viral E2 gene is often disrupted by this process, releasing suppression of viral E6/E7 oncogenes, a key factor for oncogenic progression. To evaluate the physical status of HPV 16 E2 gene in cervical preneoplastic and neoplastic lesions and its relation with lesion severity. A sensitive PCR approach for the detection of an intact E2 HPV 16 gene in infected epithelial cells from the cervix with low grade squamous intraepithelial lesion (LGSIL), high grade squamous intraepithelial lesion (HGSIL) and invasive cervical carcinoma (ICC) diagnosis was applied. The correlation between gene disruption and lesion stage was examined. Sixty-two LGSIL, 39 HGSIL and 24 ICC samples were analyzed. Fifty-seven LGSIL [92%], 13 HGSIL [33%] and 4 ICC [17%] showed results compatible with an intact E2 gene, while 5 LGSIL [8%], 26 HGSIL [67%] and 20 ICC [83%] samples gave no signal. HPV 16 E2 gene disruption showed a positive correlation with cervical lesion progression, particularly from LGSIL to HGSIL. Although additional genetic events are very likely to be needed for HGSIL to ICC progression, the E2 gene disruption is a putative early marker to consider in the prognostic analysis of HPV 16 chronically infected women.

12. Copy of early 20th century photograph showing facade, looking ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

12. Copy of early 20th century photograph showing facade, looking west. Photograph owned by Parker-Hannifin Corporation. - Cleveland-Chandler Motors Corporation, 300 East 131st Street, Cleveland, Cuyahoga County, OH

Educating K-12 Students about Glacier Dynamics in a Changing Climate

NASA Astrophysics Data System (ADS)

Stearns, L. A.; Hamilton, G. S.

2005-12-01

Public awareness of climate change is growing in the United States. Popular movies, books and magazines are frequently addressing the issue of global warming - some with careful scientific research, but many with unrealistic statements. Early education about the basic principles and processes of climate change is necessary for the general public to distinguish fact from fiction. The U.S. National Science Foundation's GK-12 program (GK-12; grades K to 12) currently in its sixth year, provides an opportunity for scientific enrichment for students and their teachers at the K-12 level through collaborative pairings with science and engineering graduate students (the Fellows). The NSF GK-12 program at the University of Maine has three goals: to enrich the scientific education of the students by providing role models, expertise, and equipment that may not be accessible otherwise; to provide professional development for the teachers through curriculum enrichment and participation at science conferences; and to improve the teaching and communication skills of the Fellows. The University of Maine is one of over 100 U. S. universities participating in this program. During the 2004-05 academic year, 11 graduate and one undergraduate student Fellows, advised by University faculty members, taught at schools across the state of Maine. Fellows from, biology, earth science, ecology, engineering, food science, forestry, and marine science, and taught in their area of expertise. We created a hands-on activity for middle and high school students that describes glacier mass balance in a changing climate. The students make a glacier using glue, water and detergent ('flubber') and construct a glacier valley using plastic sheeting. Flubber behaves in mechanically similar ways to glacier ice, undergoing plastic deformation at low stresses and exhibiting brittle failure at high stresses. Students are encouraged to run several tests with different values for valley slope, glacier mass

Lamina Cribrosa Microarchitecture in Monkey Early Experimental Glaucoma: Global Change

PubMed Central

Reynaud, Juan; Lockwood, Howard; Gardiner, Stuart K.; Williams, Galen; Yang, Hongli; Burgoyne, Claude F.

2016-01-01

Purpose The purpose of this study was to characterize experimental glaucoma (EG) versus control eye differences in lamina cribrosa (LC), beam diameter (BD), pore diameter (PD), connective tissue volume fraction (CTVF), connective tissue volume (CTV), and LC volume (LV) in monkey early EG. Methods Optic nerve heads (ONHs) of 14 unilateral EG and 6 bilateral normal (BN) monkeys underwent three-dimensional reconstruction and LC beam segmentation. Each beam and pore voxel was assigned a diameter based on the largest sphere that contained it before transformation to a common cylinder with inner, middle, and outer layers. Full-thickness and layer averages for BD, PD, CTVF, CTV, and LV were calculated for each ONH. Beam diameter and PD distributions for each ONH were fit to a gamma distribution and summarized by scale and shape parameters. Experimental glaucoma and depth effects were assessed for each parameter by linear mixed-effects (LME) modeling. Animal-specific EG versus control eye differences that exceeded the maximum intereye difference among the six BN animals were considered significant. Results Overall EG eye mean PD was 12.8% larger (28.2 ± 5.6 vs. 25.0 ± 3.3 μm), CTV was 26.5% larger (100.06 ± 47.98 vs. 79.12 ± 28.35 × 106 μm3), and LV was 40% larger (229.29 ± 98.19 vs. 163.63 ± 39.87 × 106 μm3) than control eyes (P ≤ 0.05, LME). Experimental glaucoma effects were significantly different by layer for PD (P = 0.0097) and CTVF (P < 0.0001). Pore diameter expanded consistently across all PDs. Experimental glaucoma eye-specific parameter change was variable in magnitude and direction. Conclusions Pore diameter, CTV, and LV increase in monkey early EG; however, EG eye-specific change is variable and includes both increases and decreases in BD and CTVF. PMID:27362781

New concepts of histological changes in experimental augmentation cystoplasty: insights into the development of neoplastic transformation at the enterovesical and gastrovesical anastomosis.

PubMed

Gitlin, J S; Wu, X R; Sun, T T; Ritchey, M L; Shapiro, E

1999-09-01

To our knowledge the pathogenesis of malignancy associated with ileal cystoplasty, ureterosigmoidostomy and ileal conduits is currently unknown. To gain further insights into the mechanism of neoplastic transformation we studied histological changes in a canine augmentation cystoplasty model. Enterocystoplasty and gastrocystoplasty were performed using a 5 to 7 cm. patch of ileum in 8 dogs and gastric antrum in 6. Specimens were harvested 4 months postoperatively. Representative 3 microm sections of the enterovesical and gastrovesical junctions were stained with hematoxylin and eosin. Uroplakin expression was assessed using an indirect peroxidase method subjected to double staining with alcian blue and periodic acid-Schiffreagent. The bladder portion of the augmentation cystoplasty had 3 to 4 stratified cell layers covered with a distinctive umbrella cell layer. Strong uroplakin staining was visible in all cell layers except the basal layer. At the enterovesical and gastrovesical junctions 6 to 10 layers of hyperplastic, urothelial appearing cells covered the glandular epithelium of the ileal and gastric segments. These cells expressed uroplakins. At this junction zone there was a marked decrease of underlying enteric glands, which had atrophied in proportion to the degree of urothelial hyperplasia. Double staining of uroplakin stained sections with alcian blue and periodic acid-Schiff reagent revealed mucosubstances in hyperplastic urothelial cells covering the enteral segments, indicating that the cells co-expressed uroplakins and mucins. Histological changes in this experimental canine model of augmentation cystoplasty indicated that the overgrowth of hyperplastic transitional epithelium develops at the enterovesical and gastrovesical junctions. These cells express not only uroplakins, but also mucosubstances. Our results suggest that the migrated hyperplastic urothelial cells have undergone changes characteristic of the enteric and gastric epithelium, which may

Noninvasive monitoring of photodynamic therapy on skin neoplastic lesions using the optical attenuation coefficient measured by optical coherence tomography

NASA Astrophysics Data System (ADS)

Goulart, Viviane P.; dos Santos, Moisés O.; Latrive, Anne; Freitas, Anderson Z.; Correa, Luciana; Zezell, Denise M.

2015-05-01

Photodynamic therapy (PDT) has become a promising alternative for treatment of skin lesions such as squamous cell carcinoma. We propose a method to monitor the effects of PDT in a noninvasive way by using the optical attenuation coefficient (OAC) calculated from optical coherence tomography (OCT) images. We conducted a study on mice with chemically induced neoplastic lesions and performed PDT on these lesions using homemade photosensitizers. The response of neoplastic lesions to therapy was monitored using, at the same time, macroscopic clinical visualization, histopathological analysis, OCT imaging, and OCT-based attenuation coefficient measurement. Results with all four modalities demonstrated a positive response to treatment. The attenuation coefficient was found to be 1.4 higher in skin lesions than in healthy tissue and it decreased after therapy. This study shows that the OAC is a potential tool to noninvasively assess the evolution of skin neoplastic lesions with time after treatment.

Implementing Observation Protocols: Lessons for K-12 Education from the Field of Early Childhood

ERIC Educational Resources Information Center

Pianta, Robert C.

2012-01-01

This report draws from decades of experience using observation in early childhood education, which has implications for administrative decisions, evaluation practices, and policymaking in K-12. Early childhood education has long embraced the value of observing classrooms and teacher-child interactions. In early childhood education the features of…

Later Life Changes in Hippocampal Neurogenesis and Behavioral Functions After Low-Dose Prenatal Irradiation at Early Organogenesis Stage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganapathi, Ramya; Manda, Kailash, E-mail: kailashmanda@gmail.com

Purpose: To investigate long-term changes in behavioral functions of mice after exposure to low-dose prenatal radiation at an early organogenesis stage. Methods and Materials: Pregnant C57BL/6J mice were irradiated (20 cGy) at postcoitus day 5.5. The male and female offspring were subjected to different behavioral assays for affective, motor, and cognitive functions at 3, 6, and 12 months of age. Behavioral functions were further correlated with the population of CA1 and CA3 pyramidal neurons and immature neurons in hippocampal dentate gyrus. Results: Prenatally exposed mice of different age groups showed a sex-specific pattern of sustained changes in behavioral functions. Male mice showed significantmore » changes in anxiety-like phenotypes, learning, and long-term memory at age 3 months. At 6 months of age such behavioral functions were recovered to a normal level but could not be sustained at age 12 months. Female mice showed an appreciable recovery in almost all behavioral functions at 12 months. Patterns of change in learning and long-term memory were comparable to the population of CA1 and CA3 pyramidal neurons and doublecortin-positive neurons in hippocampus. Conclusion: Our finding suggests that prenatal (early organogenesis stage) irradiation even at a lower dose level (20 cGy) is sufficient to cause potential changes in neurobehavioral function at later stages of life. Male mice showed relatively higher vulnerability to radiation-induced neurobehavioral changes as compared with female.« less

Matrix Metalloproteinases in Non-Neoplastic Disorders

PubMed Central

Tokito, Akinori; Jougasaki, Michihisa

2016-01-01

The matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases belonging to the metzincin superfamily. There are at least 23 members of MMPs ever reported in human, and they and their substrates are widely expressed in many tissues. Recent growing evidence has established that MMP not only can degrade a variety of components of extracellular matrix, but also can cleave and activate various non-matrix proteins, including cytokines, chemokines and growth factors, contributing to both physiological and pathological processes. In normal conditions, MMP expression and activity are tightly regulated via interactions between their activators and inhibitors. Imbalance among these factors, however, results in dysregulated MMP activity, which causes tissue destruction and functional alteration or local inflammation, leading to the development of diverse diseases, such as cardiovascular disease, arthritis, neurodegenerative disease, as well as cancer. This article focuses on the accumulated evidence supporting a wide range of roles of MMPs in various non-neoplastic diseases and provides an outlook on the therapeutic potential of inhibiting MMP action. PMID:27455234

Lymphatic vessel density in the neoplastic progression of Barrett's oesophagus to adenocarcinoma

PubMed Central

Brundler, M‐A; Harrison, J A; de Saussure, B; de Perrot, M; Pepper, M S

2006-01-01

Background Oesophageal adenocarcinoma is an aggressive neoplasm with poor prognosis as a result of early lymph node metastasis. Aims To measure lymphatic vessel density (LVD) in the neoplastic progression from Barrett's metaplasia to adenocarcinoma and determine whether LVD can predict the risk of cancer. In addition, to correlate LVD with lymph node metastasis and assess whether LVD could be used as a prognostic indicator for outcome or survival. Methods LVD and microvascular density (MVD) were assessed after immunohistochemical staining of vessels in Barrett's metaplasia, dysplasia, and adenocarcinoma tissues and were correlated with clinicopathological features. Results LVD was significantly reduced in adenocarcinoma, being half that seen in normal stomach/oesophagus or metaplasia/dysplasia. LVD did not correlate with tumour grade, stage, or clinical outcome; however, patients who had either lymph node metastasis or invasion of tumour cells into peritumorous lymphatic vessels had a significantly worse overall survival. MVD was also assessed as a prognostic marker; its increase appeared to be linked more with the development of Barrett's metaplasia than adenocarcinoma. Conclusions The reduction in lymphatic vessel numbers was not useful for determining disease outcome in the patient group studied. It is the entry of tumour cells into pre‐existing peritumorous lymphatic vessels that confers a significantly worse overall survival. PMID:16443737

Non-neoplastic cystic and cystic-like lesions of the pancreas: may mimic pancreatic cystic neoplasms.

PubMed

Goh, Brian K P; Tan, Yu-Meng; Chung, Yaw-Fui A; Chow, Pierce K H; Ong, Hock-Soo; Lim, Dennis T H; Wong, Wai-Keong; Ooi, London L P J

2006-05-01

Cystic lesions of the pancreas consist of a broad range of pathological entities. With the exception of the pancreatic pseudocyst, these are usually caused by pancreatic cystic neoplasms. Non-neoplastic pancreatic cystic and cystic-like lesions are extremely rare. In the present article, the surgical experience with these unusual entities over a 14-year period is reported. Between 1991 and 2004, all patients who underwent surgical exploration for a cystic lesion of the pancreas were retrospectively reviewed. Patients with a pancreatic pseudocyst were excluded. There were 106 patients of whom 8 (7.5%) had a final pathological diagnosis consistent with a non-neoplastic pancreatic cystic or cystic-like lesion, including 3 patients with a benign epithelial cyst, 2 with a pancreatic abscess (one tuberculous and one foreign body), 2 with mucous retention cysts and 1 with a mucinous non-neoplastic cyst. These eight patients are the focus of this study. There were six female and two male patients with a median age of 61.5 years (range, 41-71 years). All the patients were of Asian origin including seven Chinese and one Indian. Four of the patients were asymptomatic and their pancreatic cysts were discovered incidentally on radiological imaging for other indications. All the patients underwent preoperative radiological investigations, including ultrasonography, computed tomography or magnetic resonance imaging, which showed a cystic lesion of the pancreas. Three patients, all of whom were symptomatic, were diagnosed preoperatively with a malignant cystic neoplasm on the basis of radiological imaging. Two patients were eventually found to have a pancreatic abscess, one tuberculous and the other, secondary to foreign body perforation. The third patient was found on final histology to have chronic pancreatitis with retention cysts. The remaining five patients had a preoperative diagnosis of an indeterminate cyst; on pathological examination, they were found to have a benign

Cell-block procedure in endoscopic ultrasound-guided-fine-needle-aspiration of gastrointestinal solid neoplastic lesions

PubMed Central

Ieni, Antonio; Barresi, Valeria; Todaro, Paolo; Caruso, Rosario Alberto; Tuccari, Giovanni

2015-01-01

In the present review we have analyzed the clinical applications of endoscopic ultrasound-guided-fine-needle-aspiration (EUS-FNA) and the methodological aspects obtained by cell-block procedure (CBP) in the diagnostic approach to the gastrointestinal neoplastic pathology. CBP showed numerous advantages in comparison to the cytologic routine smears; in particular, better preservation of cell architecture, achievement of routine haematoxylin-eosin staining equivalent to histological slides and possibility to perform immunohistochemistry or molecular analyses represented the most evident reasons to choose this method. Moreover, by this approach, the differential diagnosis of solid gastrointestinal neoplasias may be more easily achieved and the background of contaminant non-neoplastic gastrointestinal avoided. Finally, biological samples collected by EUS-FNA CBP-assisted should be investigated in order to identify and quantify further potential molecular markers. PMID:26322154

Periosteal pseudotumor in complex total knee arthroplasty resembling a neoplastic process.

PubMed

Chowdhry, Madhav; Dipane, Matthew V; McPherson, Edward J

2018-05-18

This case report describes in detail an erosive distal diaphyseal pseudotumor that occurred 6 years after a complex endoprosthetic hinge total knee arthroplasty (TKA). A female patient had conversion of a knee fusion to an endoprosthetic hinge TKA at the age of 62. At her scheduled 6-year follow-up, she presented with mild distal thigh pain and radiographs showing a 6-7 cm erosive lytic diaphyseal lesion that looked very suspicious for a neoplastic process. An en bloc resection of the distal femur and femoral endoprosthesis was performed. Histologic review showed the mass to be a pseudotumor with the wear debris emanating from within the femoral canal due to distal stem loosening. We deduce that mechanized stem abrasion created microscopic titanium alloy particles that escaped via a small diaphyseal crack and stimulated an inflammatory response resulting in a periosteal erosive pseudotumor. The main lesson of this report is that, in the face of a joint replacement surgery of the knee, pseudotumor formation is a more likely diagnosis than a neoplastic process when encountering an expanding bony mass. Thus, a biopsy prior to en bloc resection, would be our recommended course of action any time a suspicious mass is encountered close to a TKA.

Early transcriptional changes in cardiac mitochondria during chronic doxorubicin exposure and mitigation by dexrazoxane in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vijay, Vikrant; Moland, Carrie L.; Han, Tao

Identification of early biomarkers of cardiotoxicity could help initiate means to ameliorate the cardiotoxic actions of clinically useful drugs such as doxorubicin (DOX). Since DOX has been shown to target mitochondria, transcriptional levels of mitochondria-related genes were evaluated to identify early candidate biomarkers in hearts of male B6C3F{sub 1} mice given a weekly intravenous dose of 3 mg/kg DOX or saline (SAL) for 2, 3, 4, 6, or 8 weeks (6, 9, 12, 18, or 24 mg/kg cumulative DOX doses, respectively). Also, a group of mice was pretreated (intraperitoneally) with the cardio-protectant, dexrazoxane (DXZ; 60 mg/kg) 30 min before eachmore » weekly dose of DOX or SAL. At necropsy a week after the last dose, increased plasma concentrations of cardiac troponin T (cTnT) were detected at 18 and 24 mg/kg cumulative DOX doses, whereas myocardial alterations were observed only at the 24 mg/kg dose. Of 1019 genes interrogated, 185, 109, 140, 184, and 451 genes were differentially expressed at 6, 9, 12, 18, and 24 mg/kg cumulative DOX doses, respectively, compared to concurrent SAL-treated controls. Of these, expression of 61 genes associated with energy metabolism and apoptosis was significantly altered before and after occurrence of myocardial injury, suggesting these as early genomics markers of cardiotoxicity. Much of these DOX-induced transcriptional changes were attenuated by pretreatment of mice with DXZ. Also, DXZ treatment significantly reduced plasma cTnT concentration and completely ameliorated cardiac alterations induced by 24 mg/kg cumulative DOX. This information on early transcriptional changes during DOX treatment may be useful in designing cardioprotective strategies targeting mitochondria. - Highlights: • Altered mitochondria-related gene expression before heart injury by doxorubicin • Dexrazoxane mitigated doxorubicin-induced early expression changes in mitochondria. • Dexrazoxane completely ameliorated doxorubicin-induced pathology in mouse

Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases.

PubMed Central

Lucey, D R; Clerici, M; Shearer, G M

1996-01-01

In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for

The CGL1 (HeLa × Normal Skin Fibroblast) Human Hybrid Cell Line: A History of Ionizing Radiation Induced Effects on Neoplastic Transformation and Novel Future Directions in SNOLAB.

PubMed

Pirkkanen, Jake S; Boreham, Douglas R; Mendonca, Marc S

2017-10-01

Cellular transformation assays have been utilized for many years as powerful in vitro methods for examining neoplastic transformation potential/frequency and mechanisms of carcinogenesis for both chemical and radiological carcinogens. These mouse and human cell based assays are labor intensive but do provide quantitative information on the numbers of neoplastically transformed foci produced after carcinogenic exposure and potential molecular mechanisms involved. Several mouse and human cell systems have been generated to undertake these studies, and they vary in experimental length and endpoint assessment. The CGL1 human cell hybrid neoplastic model is a non-tumorigenic pre-neoplastic cell that was derived from the fusion of HeLa cervical cancer cells and a normal human skin fibroblast. It has been utilized for the several decades to study the carcinogenic/neoplastic transformation potential of a variety of ionizing radiation doses, dose rates and radiation types, including UV, X ray, gamma ray, neutrons, protons and alpha particles. It is unique in that the CGL1 assay has a relatively short assay time of 18-21 days, and rather than relying on morphological endpoints to detect neoplastic transformation utilizes a simple staining method that detects the tumorigenic marker alkaline phosphatase on the neoplastically transformed cells cell surface. In addition to being of human origin, the CGL1 assay is able to detect and quantify the carcinogenic potential of very low doses of ionizing radiation (in the mGy range), and utilizes a neoplastic endpoint (re-expression of alkaline phosphatase) that can be detected on both viable and paraformaldehyde fixed cells. In this article, we review the history of the CGL1 neoplastic transformation model system from its initial development through the wide variety of studies examining the effects of all types of ionizing radiation on neoplastic transformation. In addition, we discuss the potential of the CGL1 model system to

Animal models of neoplastic development.

PubMed

Pitot, H C

2001-01-01

The basic animal model for neoplastic development used by regulatory agencies is the two-year chronic bioassay developed more than 30 years ago and based on the presumed mechanism of action of a few potential chemical carcinogens. Since that time, a variety of other model carcinogenic systems have been developed, usually involving shorter duration, single organ endpoints, multistage models, and those in genetically-engineered mice. The chronic bioassay is still the "gold standard" of regulatory agencies despite a number of deficiencies, while in this country the use of shorter term assays based on single organ endpoints has not been popular. The multistage model of carcinogenesis in mouse epidermis actually preceded the development of the chronic two-year bioassay, but it was not until multistage models in other organ systems were developed that the usefulness of such systems became apparent. Recently, several genetically-engineered mouse lines involving mutations in proto-oncogenes and tumour suppressor genes have been proposed as additional model systems for use in regulatory decisions. It is likely that a combination of several of these model systems may be most useful in both practical and basic applications of cancer prevention and therapy.

Postirradiation malignant fibrous histiocytoma of the lung. Demonstration of alpha 1-antitrypsin-like material in neoplastic cells.

PubMed

Chowdhury, L N; Swerdlow, M A; Jao, W; Kathpalia, S; Desser, R K

1980-12-01

A metastasizing fibrous histiocytoma arising in the lung of a patient who received radiation therapy and long-term chemotherapy for malignant lymphoma is presented. Ultrastructural studies revealed fibroblast-like and histiocyte-like cells, cells of intermediate type showing ultrastructural features of both fibroblast-like and histiocyte-like cells, primitive mesenchymal cells, multinucleate tumor cells, and xanthomatous cells. The neoplastic cells showed dilated rough endoplasmic reticula with intracisternal accumulation of electron-dense material forming lattice-like structures. Direct immunofluorescence staining of the neoplastic cells using antihuman alpha 1-antitrypsin showed specific activity, with fluorescent deposits exhibiting interlacing globular formations. These findings and their implications are discussed.

Hormone Receptor Expression Analyses in Neoplastic and Non-Neoplastic Canine Mammary Tissue by a Bead Based Multiplex Branched DNA Assay: A Gene Expression Study in Fresh Frozen and Formalin-Fixed, Paraffin-Embedded Samples.

PubMed

Mohr, Annika; Lüder Ripoli, Florenza; Hammer, Susanne Conradine; Willenbrock, Saskia; Hewicker-Trautwein, Marion; Kiełbowicz, Zdzisław; Murua Escobar, Hugo; Nolte, Ingo

2016-01-01

Immunohistochemistry (IHC) is currently considered the method of choice for steroid hormone receptor status evaluation in human breast cancer and, therefore, it is commonly utilized for assessing canine mammary tumors. In case of low hormone receptor expression, IHC is limited and thus is complemented by molecular analyses. In the present study, a multiplex bDNA assay was evaluated as a method for hormone receptor gene expression detection in canine mammary tissues. Estrogen receptor (ESR1), progesterone receptor (PGR), prolactin receptor (PRLR) and growth hormone receptor (GHR) gene expressions were evaluated in neoplastic and non-neoplastic canine mammary tissues. A set of 119 fresh frozen and 180 formalin-fixed, paraffin-embedded (FFPE) was comparatively analyzed and used for assay evaluation. Furthermore, a possible association between the hormone receptor expression in different histological subtypes of canine malignant mammary tumors and the castration status, breed and invasive growth of the tumor were analyzed. The multiplex bDNA assay proved to be more sensitive for fresh frozen specimens. Hormone receptor expression found was significantly decreased in malignant mammary tumors in comparison to non-neoplastic tissue and benign mammary tumors. Among the histological subtypes the lowest gene expression levels of ESR1, PGR and PRLR were found in solid, anaplastic and ductal carcinomas. In summary, the evaluation showed that the measurement of hormone receptors with the multiplex bDNA assay represents a practicable method for obtaining detailed quantitative information about gene expression in canine mammary tissue for future studies. Still, comparison with IHC or quantitative real-time PCR is needed for further validation of the present method.

12 CFR Appendix Ms - 4-Model Clauses for the Written Early Intervention Notice

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 8 2014-01-01 2014-01-01 false 4-Model Clauses for the Written Early Intervention Notice MS Appendix MS Banks and Banking BUREAU OF CONSUMER FINANCIAL PROTECTION REAL ESTATE...-4 Appendix MS-4—Model Clauses for the Written Early Intervention Notice MS-4(A)—Statement...

Weight changes after adjuvant treatment in Korean women with early breast cancer.

PubMed

Han, Hye-Suk; Lee, Keun-Wook; Kim, Jee Hyun; Kim, Sung-Won; Kim, In-Ah; Oh, Do-Youn; Im, Seock-Ah; Bang, Soo-Mee; Lee, Jong Seok

2009-03-01

Weight gain is a common problem in breast cancer patients and is reported to be associated with poorer survival. However, most data are limited to Western women. We evaluated weight changes after adjuvant treatment in Korean women with early breast cancer. The authors reviewed the records of 260 patients with stage I-III breast cancer treated between June 2003 and February 2006. Body weight, body mass index (BMI) and menopausal status at baseline and after 3, 6, 12 and 24 months of adjuvant treatment were reviewed. Mean patient age was 47.0 years and 61.1% of women were premenopausal. Among them, 195 patients (75.8%) received chemotherapy and 186 (71.5%) received hormonal therapy. Mean baseline weight was 57.5 +/- 9.8 kg and mean BMI was 23.5 +/- 1.6 kg/m(2) (22.8 +/- 3.0 vs. 24.7 +/- 3.2 kg/m(2) for pre- vs. post-menopausal women, P = 0.286). Mean weight changes were; 0.30 kg at 3 months (P = 0.019); 0.16 kg at 6 months (P = 0.367); -0.34 kg at 1 year (P = 0.082); -0.40 kg at 2 years (P = 0.097). Twenty-three patients (10.4%) gained more than 5% of baseline body weight at 1 year, but no clinical variable was found to be associated with these weight gains. This study shows that Korean women with early breast cancer do not gain weight after adjuvant treatment. Further studies are needed to determine differences between Asian and Western women in terms of weight changes and prognosis in early breast cancer.

Rheological changes of polyamide 12 under oscillatory shear

NASA Astrophysics Data System (ADS)

Mielicki, C.; Gronhoff, B.; Wortberg, J.

2014-05-01

Changes in material properties as well as process deviation prevent Laser Sintering (LS) technology from manufacturing of quality assured parts in a series production. In this context, the viscosity of Polyamide 12 (PA12) is assumed to possess the most significant influence, as it determines the sintering velocity, the resistance towards melt formation and the bonding strength of sintered layers. Moreover, the viscosity is directly related to the structure of the molten polymer. In particular, it has been recently reported that LS process conditions lead to structural changes of PA12 affecting viscosity and coalescence of adjacent polymer particles, i.e. melt formation significantly. Structural change of PA12 was understood as a post condensation. Its influence on viscosity was described by a time and temperature depending rheological model whereas time dependence was considered by a novel structural change shift factor which was derived from melt volume rate data. In combination with process data that was recorded using online thermal imaging, the model is suitable to control the viscosity (processability of the material) as result of material and process properties. However, as soon as laser energy is exposed to the powder bed PA12 undergoes a phase transition from solid to molten state. Above the melting point, structural change is expected to occur faster due to a higher kinetic energy and free volume of the molten polymer. Oscillatory shear results were used to study the influence of aging time and for validation of the novel structural change shift factor and its model parameters which were calibrated based on LS processing condition.

Early Childhood Inclusion: Focus on Change.

ERIC Educational Resources Information Center

Guralnick, Michael J., Ed.

Early childhood inclusion is a field characterized by a philosophy and practice that encourages full participation of children with disabilities and their families in everyday activities with their typically developing peers. Noting that success in inclusion endeavors requires substantial changes in the way our society thinks, feels, and acts,…

Near-infrared Raman spectroscopy for estimating biochemical changes associated with different pathological conditions of cervix

NASA Astrophysics Data System (ADS)

Daniel, Amuthachelvi; Prakasarao, Aruna; Ganesan, Singaravelu

2018-02-01

The molecular level changes associated with oncogenesis precede the morphological changes in cells and tissues. Hence molecular level diagnosis would promote early diagnosis of the disease. Raman spectroscopy is capable of providing specific spectral signature of various biomolecules present in the cells and tissues under various pathological conditions. The aim of this work is to develop a non-linear multi-class statistical methodology for discrimination of normal, neoplastic and malignant cells/tissues. The tissues were classified as normal, pre-malignant and malignant by employing Principal Component Analysis followed by Artificial Neural Network (PC-ANN). The overall accuracy achieved was 99%. Further, to get an insight into the quantitative biochemical composition of the normal, neoplastic and malignant tissues, a linear combination of the major biochemicals by non-negative least squares technique was fit to the measured Raman spectra of the tissues. This technique confirms the changes in the major biomolecules such as lipids, nucleic acids, actin, glycogen and collagen associated with the different pathological conditions. To study the efficacy of this technique in comparison with histopathology, we have utilized Principal Component followed by Linear Discriminant Analysis (PC-LDA) to discriminate the well differentiated, moderately differentiated and poorly differentiated squamous cell carcinoma with an accuracy of 94.0%. And the results demonstrated that Raman spectroscopy has the potential to complement the good old technique of histopathology.

Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease.

PubMed

Stout, Julie C; Jones, Rebecca; Labuschagne, Izelle; O'Regan, Alison M; Say, Miranda J; Dumas, Eve M; Queller, Sarah; Justo, Damian; Santos, Rachelle Dar; Coleman, Allison; Hart, Ellen P; Dürr, Alexandra; Leavitt, Blair R; Roos, Raymund A; Langbehn, Doug R; Tabrizi, Sarah J; Frost, Chris

2012-07-01

Deterioration of cognitive functioning is a debilitating symptom in many neurodegenerative diseases, such as Huntington's disease (HD). To date, there are no effective treatments for the cognitive problems associated with HD. Cognitive assessment outcomes will have a central role in the efforts to develop treatments to delay onset or slow the progression of the disease. The TRACK-HD study was designed to build a rational basis for the selection of cognitive outcomes for HD clinical trials. There were a total of 349 participants, including controls (n=116), premanifest HD (n=117) and early HD (n=116). A standardised cognitive assessment battery (including nine cognitive tests comprising 12 outcome measures) was administered at baseline, and at 12 and 24 months, and consisted of a combination of paper and pencil and computerised tasks selected to be sensitive to cortical-striatal damage or HD. Each cognitive outcome was analysed separately using a generalised least squares regression model. Results are expressed as effect sizes to permit comparisons between tasks. 10 of the 12 cognitive outcomes showed evidence of deterioration in the early HD group, relative to controls, over 24 months, with greatest sensitivity in Symbol Digit, Circle Tracing direct and indirect, and Stroop word reading. In contrast, there was very little evidence of deterioration in the premanifest HD group relative to controls. The findings describe tests that are sensitive to longitudinal cognitive change in HD and elucidate important considerations for selecting cognitive outcomes for clinical trials of compounds aimed at ameliorating cognitive decline in HD.

CDX1 protein expression in normal, metaplastic, and neoplastic human alimentary tract epithelium.

PubMed

Silberg, D G; Furth, E E; Taylor, J K; Schuck, T; Chiou, T; Traber, P G

1997-08-01

CDX1 is an intestine-specific transcription factor expressed early in intestinal development that may be involved in regulation of proliferation and differentiation of intestinal epithelial cells. We examined the pattern of CDX1 protein expression in metaplastic and neoplastic tissue to provide insight into its possible role in abnormal differentiation. Tissue samples were stained by immunohistochemistry using an affinity-purified, polyclonal antibody against a peptide epitope of CDX1. Specific nuclear staining was found in epithelial cells of the small intestine and colon. Esophagus and stomach did not express CDX1 protein; however, adjacent areas of intestinal metaplastic tissue intensely stained for CDX1. Adenocarcinomas of the stomach and esophagus had both positive and negative nuclear staining for CDX1. Colonic epithelial cells in adenomatous polyps and adenocarcinomas had a decreased intensity of staining compared with normal colonic crypts in the same specimen. CDX1 may be important in the transition from normal gastric and esophageal epithelium to intestinal-type metaplasia. The variability in expression of CDX1 in gastric and esophageal adenocarcinomas suggests more than one pathway in the development of these carcinomas. The decrease of CDX1 in colonic adenocarcinomas may indicate a role for CDX1 in growth regulation and in the maintenance of the differentiated phenotype.

[Role of totally implantable systems for long-term vascular access in the treatment of the neoplastic patient].

PubMed

Aldrighetti, L; Caterini, R; Ronzoni, M; Jannello, A; Ferla, G

1995-05-01

To assess retrospectively the effectiveness, the safety and the impact on the quality of life of the Subcutaneous Infusion Ports (SIPs) for prolonged venous access in the treatment of neoplastic patients. Retrospective analysis of a case series collected-during 30 months (April 1991-September 1993). General Surgery Division and Radiochemotherapy Service. 35 patients (23 male, 12 female), aged between 27-80 years, received 37 SIPs. 2 patients received 2 SIPs. 34 patients were affected by neoplasm; 1 patient had short gut syndrome secondary to massive small bowel resection. The SIP was implanted in all patients in the operating room with the Seldinger technique ("catheter over wire"). The suclavian vein, through an infraclavicular approach, was the only site of venous access. One SIP was implanted in the hepatic artery. All neoplastic patients received chemotherapy. The patient with short gut syndrome had parenteral nutrition. An external infusion device (CADD-1, CADD-plus, Pharmacia) was used in 13 patients for the continuous infusion of either 5-Fluoro-Uracil (1000 mg/m2/die for 5 days, every 28 days) or 5-Fluoro-Deoxy-Uridine (0.15-0.30 mg/kg/die for 14 days, every 28 days). SIP management required the port "flush" with normal saline solution with heparin (100 U/ml) at least every 40 days, using Huber needle. All patients were treated as outpatients. All intraoperative and long-term complications, recorded in the charts of the patients, were reviewed. The rate of intraoperative complications was assessed over 37 procedures. Long-term complications were assessed over 28 patients (7 patients were excluded for lack of follow up data). Incidence of complications was analyzed over patient days, considering the cumulative permanence time of the SIP in a single patient. We recorded 4 intraoperative complications (10.8%). None of them required to stop the procedure and to delay the implant of the SIP. During the follow-up period (range 1-18 months) we had 1 major

Early changes in coronary artery wall structure detected by microcomputed tomography in experimental hypercholesterolemia.

PubMed

Zhu, Xiang-Yang; Bentley, Michael D; Chade, Alejandro R; Ritman, Erik L; Lerman, Amir; Lerman, Lilach O

2007-09-01

Changes in the structure of the artery wall commence shortly after exposure to cardiovascular risk factors, such as hypercholesterolemia (HC), but may be difficult to detect. The ability to study vascular wall structure could be helpful in evaluation of the factors that instigate atherosclerosis and its pathomechanisms. The present study tested the hypothesis that early morphological changes in coronary arteries of hypercholesterolemic (HC) pigs can be detected using the novel X-ray contrast agent OsO(4) and three-dimensional micro-computed tomography (CT). Two groups of pigs were studied after they were fed a normal or an HC (2% cholesterol) diet for 12 wk. Hearts were harvested, coronary arteries were injected with 1% OsO(4) solution, and cardiac samples (6-mum-thick) were scanned by micro-CT. Layers of the epicardial coronary artery wall, early lesions, and perivascular OsO(4) accumulation were determined. Leakage of OsO(4) from myocardial microvessels was used to assess vascular permeability, which was correlated with immunoreactivity of vascular endothelial growth factor in corresponding histological cross sections. OsO(4) enhanced the visualization of coronary artery wall layers and facilitated detection of early lesions in HC in longitudinal tomographic sections of vascular segments. Increased density of perivascular OsO(4) in HC was correlated with increased vascular endothelial growth factor expression and suggested increased microvascular permeability. The use of OsO(4) as a contrast agent in micro-CT allows three-dimensional visualization of coronary artery wall structure, early lesion formation, and changes in vascular permeability. Therefore, this technique can be a useful tool in atherosclerosis research.

Topical Collection: Climate-change research by early-career hydrogeologists

NASA Astrophysics Data System (ADS)

Re, Viviana; Maldaner, Carlos H.; Gurdak, Jason J.; Leblanc, Marc; Resende, Tales Carvalho; Stigter, Tibor Y.

2018-05-01

Scientific outreach, international networking, collaboration and adequate courses are needed in both developed and developing countries to enable early-career hydrogeologists to promote long-term multidisciplinary approaches to cope with climate-change issues and emphasize the importance of groundwater in a global strategy for adaptation. One such collaboration has involved the Early Career Hydrogeologists' Network of the International Association of Hydrogeologists (ECHN-IAH) and the UNESCO International Hydrological Programme's (IHP) Groundwater Resources Assessment under the Pressures of Humanity and Climate Changes (GRAPHIC) project. This collaboration seeks to foster the education and involvement of the future generation of water leaders in the debate over groundwater and climate change.

Low plasma selenium concentration is associated with elevated risk to neoplastic polyps of the colon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, L.C.; Hixson, L.G.; Sampliner, R.E.

1991-03-11

A cross-sectional study was conducted to examine the relationship of selenium (Se) status and polyps incidence in a sequential series of 100 patients undergoing outpatient colonoscopies at the Tucson VA Hospital. Se was measured in plasma samples by electrothermal atomic absorption spectrophotometry with Zeeman background correction using a reduced palladium matrix modified. The activities of the Se-dependent enzyme glutathione peroxidase (SeGSHpx) were measured using H{sub 2}O{sub 2} as substrate in all plasma samples and in colonic mucosal biopsies obtained from some patients. The mean plasma Se concentration of patients without polyps was 134 ng/ml. Mean plasma Se levels of patientsmore » with only diminutive or large polyps were 127 ng/ml and 125 ng/ml; while patients with polyps of both sizes had a mean plasma Se level of 121 ng/ml. Patients with no reported history of cancer, neoplastic polyps or prior colonoscopy, showed an inverse association of plasma Se level and risk of benign colonic neoplasms. The age-adjusted odds ratio for neoplastic polyps was 3.8 for patients with plasma Se levels below vs. above the median value. This association was stronger for patients under 68 yrs of age than for older patients. Activities of SeGSHpx in plasma or colonic mucosa were not related to plasma Se level; however, smokers showed greater SeGSHpx activities than non-smokers. This study is the first to detect an association of Se status and risk to neoplastic polyps of the colon.« less

MELATONIN ENHANCES JUNCTIONAL TRANSFER IN NORMAL C3H/1OT1/2 CELLS

EPA Science Inventory

There is strong evidence that pineal melatonin is involved in controlling neoplastic processes. e have reported that physiological, but not pharmacological or subphysiological, concentrations of melatonin enhance intercellular communication in normal C3H/1OT1/2 fibroblasts. ap ju...

30 CFR 33.12 - Changes after certification.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Changes after certification. 33.12 Section 33.12 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS DUST COLLECTORS FOR USE IN CONNECTION WITH ROCK DRILLING IN COAL MINES...

30 CFR 33.12 - Changes after certification.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Changes after certification. 33.12 Section 33.12 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS DUST COLLECTORS FOR USE IN CONNECTION WITH ROCK DRILLING IN COAL MINES...

30 CFR 33.12 - Changes after certification.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Changes after certification. 33.12 Section 33.12 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS DUST COLLECTORS FOR USE IN CONNECTION WITH ROCK DRILLING IN COAL MINES...

Enhanced Expression of CD13 in Vessels of Inflammatory and Neoplastic Tissues

PubMed Central

Matteo, Paola Di; Arrigoni, Gian Luigi; Alberici, Luca; Corti, Angelo; Gallo-Stampino, Corrado; Traversari, Catia; Doglioni, Claudio; Rizzardi, Gian-Paolo

2011-01-01

Aminopeptidase-N (CD13) is an important target of tumor vasculature-targeting drugs. The authors investigated its expression by immunohistochemistry with three anti-CD13 monoclonal antibodies (WM15, 3D8, and BF10) in normal and pathological human tissues, including 58 normal, 32 inflammatory, and 149 tumor tissue specimens. The three antibodies stained vessels in most neoplastic tissues, interestingly with different patterns. As a matter of fact, WM15 stained almost all intratumor and peritumor capillaries and only partially large vessels, whereas BF10 and 3D8 reacted with arteries and venules and to a lesser extent with capillaries. These antibodies also stained the stroma in about half of neoplastic tissues. In inflammatory lesions, the three antibodies stained vessels and stroma, whereas in normal tissues, they stained a small percentage of blood vessels. Finally, the three antibodies failed to stain endothelial cells of normal colon, whereas they reacted with activated human umbilical vein endothelial cells and with endothelial cells of colon adenocarcinoma vessels. Overall, WM15 was the most specific antibody for angiogenic tumor vessels, suggesting that it may be a good tool for detecting the CD13 form associated with the tumor vasculature. This finding may be relevant for CD13-mediated vascular targeting therapies. PMID:21339174

Resilience in Change: Positive Perspectives on the Dynamics of Change in Early Childhood Systems

ERIC Educational Resources Information Center

Douglass, Anne

2016-01-01

Change is a central feature of the early care and education landscape today. Much of the research on educational change focuses on the negative or challenging aspects of change. This study employed a critical theory framework from the organizational sciences field, positive organizational scholarship, to offer a new way of thinking about change in…

30 CFR 41.12 - Changes; notification by operator.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Changes; notification by operator. 41.12 Section 41.12 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR FILING AND OTHER ADMINISTRATIVE REQUIREMENTS NOTIFICATION OF LEGAL IDENTITY Notification of Legal Identity § 41.12...

30 CFR 41.12 - Changes; notification by operator.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Changes; notification by operator. 41.12 Section 41.12 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR FILING AND OTHER ADMINISTRATIVE REQUIREMENTS NOTIFICATION OF LEGAL IDENTITY Notification of Legal Identity § 41.12...

Alterations in human milk leptin and insulin are associated with early changes in the infant intestinal microbiome12

PubMed Central

Lemas, Dominick J; Young, Bridget E; Baker, Peter R; Tomczik, Angela C; Soderborg, Taylor K; Hernandez, Teri L; de la Houssaye, Becky A; Robertson, Charles E; Rudolph, Michael C; Ir, Diana; Patinkin, Zachary W; Krebs, Nancy F; Santorico, Stephanie A; Weir, Tiffany; Barbour, Linda A; Frank, Daniel N; Friedman, Jacob E

2016-01-01

Background: Increased maternal body mass index (BMI) is a robust risk factor for later pediatric obesity. Accumulating evidence suggests that human milk (HM) may attenuate the transfer of obesity from mother to offspring, potentially through its effects on early development of the infant microbiome. Objectives: Our objective was to identify early differences in intestinal microbiota in a cohort of breastfeeding infants born to obese compared with normal-weight (NW) mothers. We also investigated relations between HM hormones (leptin and insulin) and both the taxonomic and functional potentials of the infant microbiome. Design: Clinical data and infant stool and fasting HM samples were collected from 18 NW [prepregnancy BMI (in kg/m2) <24.0] and 12 obese (prepregnancy BMI >30.0) mothers and their exclusively breastfed infants at 2 wk postpartum. Infant body composition at 2 wk was determined by air-displacement plethysmography. Infant gastrointestinal microbes were estimated by using 16S amplicon and whole-genome sequencing. HM insulin and leptin were determined by ELISA; short-chain fatty acids (SCFAs) were measured in stool samples by using gas chromatography. Power was set at 80%. Results: Infants born to obese mothers were exposed to 2-fold higher HM insulin and leptin concentrations (P < 0.01) and showed a significant reduction in the early pioneering bacteria Gammaproteobacteria (P = 0.03) and exhibited a trend for elevated total SCFA content (P < 0.06). Independent of maternal prepregnancy BMI, HM insulin was positively associated with both microbial taxonomic diversity (P = 0.03) and Gammaproteobacteria (e.g., Enterobacteriaceae; P = 0.04) and was negatively associated with Lactobacillales (e.g., Streptococcaceae; P = 0.05). Metagenomic analysis showed that HM leptin and insulin were associated with decreased bacterial proteases, which are implicated in intestinal permeability, and reduced concentrations of pyruvate kinase, a biomarker of pediatric

Limbic grey matter changes in early Parkinson's disease.

PubMed

Li, Xingfeng; Xing, Yue; Schwarz, Stefan T; Auer, Dorothee P

2017-05-02

The purpose of this study was to investigate local and network-related changes of limbic grey matter in early Parkinson's disease (PD) and their inter-relation with non-motor symptom severity. We applied voxel-based morphometric methods in 538 T1 MRI images retrieved from the Parkinson's Progression Markers Initiative website. Grey matter densities and cross-sectional estimates of age-related grey matter change were compared between subjects with early PD (n = 366) and age-matched healthy controls (n = 172) within a regression model, and associations of grey matter density with symptoms were investigated. Structural brain networks were obtained using covariance analysis seeded in regions showing grey matter abnormalities in PD subject group. Patients displayed focally reduced grey matter density in the right amygdala, which was present from the earliest stages of the disease without further advance in mild-moderate disease stages. Right amygdala grey matter density showed negative correlation with autonomic dysfunction and positive with cognitive performance in patients, but no significant interrelations were found with anxiety scores. Patients with PD also demonstrated right amygdala structural disconnection with less structural connectivity of the right amygdala with the cerebellum and thalamus but increased covariance with bilateral temporal cortices compared with controls. Age-related grey matter change was also increased in PD preferentially in the limbic system. In conclusion, detailed brain morphometry in a large group of early PD highlights predominant limbic grey matter deficits with stronger age associations compared with controls and associated altered structural connectivity pattern. This provides in vivo evidence for early limbic grey matter pathology and structural network changes that may reflect extranigral disease spread in PD. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2017 The

Early Life Factors and Adult Leisure Time Physical Inactivity Stability and Change.

PubMed

Pinto Pereira, Snehal M; Li, Leah; Power, Chris

2015-09-01

Physical inactivity has a high prevalence and associated disease burden. A better understanding of influences on sustaining and changing inactive lifestyles is needed. We aimed to establish whether leisure time inactivity was stable in midadulthood and whether early life factors were associated with inactivity patterns. In the 1958 British birth cohort (n = 12,271), leisure time inactivity (frequency, less than once a week) assessed at 33 and 50 yr was categorized as "never inactive," "persistently inactive," "deteriorating," or "improving." Early life factors (birth to 16 yr) were categorized into three (physical, social, and behavioral) domains. Using multinomial logistic regression, we assessed associations with inactivity persistence and change of factors within each early life domain and the three domains combined with and without adjustment for adult factors. Inactivity prevalence was similar at 33 and 50 yr (approximately 31%), but 17% deteriorated and 18% improved with age. In models adjusted for all domains simultaneously, factors associated with inactivity persistence versus never inactive were prepubertal stature (8% lower risk/height SD), poor hand control/coordination (17% higher risk/increase on four-point scale), cognition (16% lower/SD in ability) (physical); parental divorce (25% higher), class at birth (7% higher/reduction on four-point scale), minimal parental education (16% higher), household amenities (2% higher/increase in 19-point score (high = poor)) (social); and inactivity (22% higher/reduction in activity on four-point scale), low sports aptitude (47% higher), smoking (30% higher) (behavioral). All except stature, parental education, sports aptitude, and smoking were associated also with inactivity deterioration. Poor hand control/coordination was the only factor associated with improved status (13% lower/increase on four-point scale) versus persistently inactive. Adult leisure time inactivity is moderately stable. Early life factors are

Early changes in somatosensory function in spinal pain: protocol for a systematic review.

PubMed

Marcuzzi, Anna; Dean, Catherine M; Hush, Julia M

2013-10-02

Back and neck pain are common conditions that have a high burden of disease. Changes in somatosensory function in the periphery, the spinal cord and the brain have been well documented at the time when these conditions have become chronic. It is unknown, however, how early these changes occur, what the timecourse is of sensory dysfunction and what the specific nature of these changes are in the first 12 weeks after onset of pain. In this paper, we describe the protocol for a systematic review of the literature on somatosensory dysfunction in the first 12 weeks after pain onset. We will conduct a comprehensive search for articles indexed in the databases Ovid MEDLINE, Ovid Embase, Ovid PsycINFO and Cochrane Central Register of Controlled Trial (CENTRAL) from their inception to August 2013 that report on any aspect of somatosensory function in acute or subacute neck or back pain. Two independent reviewers will screen studies for eligibility, assess risk of bias and extract relevant data. Results will be tabulated and a narrative synthesis of the results conducted. Currently, there is a gap in our knowledge about the timing of somatosensory changes in back and neck pain. The systematic review outlined in this protocol aims to address this knowledge gap and inform developments in diagnostic tools and pain mechanism-based treatments. Our protocol has been registered on PROSPERO, CRD42013005113.

Morphological, Histochemical, Immunohistochemical, and Ultrastructural Characterization of Tumors and Dysplastic and Non-Neoplastic Lesions Arising in BK Virus/tat Transgenic Mice

PubMed Central

Altavilla, Giuseppe; Trabanelli, Cecilia; Merlin, Michela; Caputo, Antonella; Lanfredi, Massimo; Barbanti-Brodano, Giuseppe; Corallini, Alfredo

1999-01-01

To study the role in AIDS pathogenesis of the human immunodeficiency virus type 1 (HIV-1) Tat protein, a transactivator of viral and cellular genes, we generated transgenic mice with a recombinant DNA containing BK virus (BKV) early region and the HIV-1 tat gene, directed by its own promoter-enhancer. DNA hybridization revealed that the transgene is stably maintained in all organs of transgenic mice as a tandem insertion in a number of copies ranging from 5 to 20 per cell. In addition, tat and BKV RNA were expressed in all tissues. Transgenic mice developed three types of lesions: 1) tumors, 2) hyperplastic and dysplastic lesions, and 3) non-neoplastic lesions. Tumors of different histotypes, such as lymphomas, adenocarcinomas of skin glands, leiomyosarcomas, skin squamous cell carcinomas, hepatomas, hepatocarcinomas, and cavernous liver hemangiomas, developed in 29% of transgenic animals. The majority of tumors were malignant, invasive, and producing metastases. Conversely, tumors of only two histotypes (lymphomas and adenocarcinomas of skin glands) appeared in control mice. Hyperplastic and dysplastic lesions were more frequent in transgenic than in control mice and involved the skin or its adnexes, the liver and the rectum, indicating multiple targets for the activity of the transgene. Pyelonephritis, frequently complicated with hydronephrosis, inflammatory eye lesions, and amyloid depositions represented the most frequent non-neoplastic lesions detected in transgenic mice. Many of the pathological findings observed in this animal model are comparable to similar lesions appearing in AIDS patients, suggesting a relevant role for Tat in the pathogenesis of such lesions during the course of AIDS. PMID:10233861

Anti-neoplastic activity of Amblyomma sculptum, Amblyomma parvum and Rhipicephalus sanguineus tick saliva on breast tumor cell lines.

PubMed

Sousa, Ana Carolina Prado; Oliveira, Carlo José Freire; Szabó, Matias Pablo Juan; Silva, Marcelo José Barbosa

2018-06-15

Cancer is one of the most troubling diseases and is becoming increasingly common. Breast cancer has a high cure rate when diagnosed early, but when diagnosed late, treatment is frequently painful, devastating and unsuccessful. The search for new treatments that are more effective and less harmful has led to several substances and biomolecules from plants and animals with potential anti-tumor activity. Within this context, ticks have emerged as an excellent source of new molecules with a wide array of therapeutic properties. Various molecules in tick saliva have immunomodulatory, anticoagulant, anti-inflammatory and anti-tumor effects across different tumor cell lines. Our study evaluates the effect of saliva from three widespread and important tick species in Brazil (Amblyomma sculptum, Amblyomma parvum and Rhipicephalus sanguineus) on MCF-7, MDA-MB-231 breast cancer cell lines and on the non-neoplastic MCF-10A cell line. We found that tick saliva from all three tick species showed cytotoxicity to tumor cells (MCF-7, MDA-MB-231) but not to the non-tumor cells (MCF-10A). Morphological changes on the surface of MCF-7 and MDA-MB-231 tumor cells did not occur on the MCF-10A cells. We also demonstrated that tumor cells die by apoptosis induced by caspase-3 and caspase 7 activity, suggesting that intrinsic pathway apoptosis may be triggered by tick saliva. These changes were not observed in MCF10A cells, which remained broadly unchanged even after exposure to diverse types of saliva. These results suggest that tick saliva from these tick species is a source of molecules, or biomolecules, useful for the potential source for the development of new breast cancer drugs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Althaea rosea Cavanil and Plantago major L. suppress neoplastic cell transformation through the inhibition of epidermal growth factor receptor kinase.

PubMed

Choi, Eun-Sun; Cho, Sung-Dae; Shin, Ji-Ae; Kwon, Ki Han; Cho, Nam-Pyo; Shim, Jung-Hyun

2012-10-01

For thousands of years in Asia, Althaea rosea Cavanil (ARC) and Plantago major L. (PML) have been used as powerful non-toxic therapeutic agents that inhibit inflammation. However, the anticancer mechanisms and molecular targets of ARC and PML are poorly understood, particularly in epidermal growth factor (EGF)-induced neoplastic cell transformation. The aim of this study was to evaluate the chemopreventive effects and mechanisms of the methanol extracts from ARC (MARC) and PML (MPML) in EGF-induced neoplastic cell transformation of JB6 P+ mouse epidermal cells using an MTS assay, anchorage-independent cell transformation assay and western blotting. Our results showed that MARC and MPML significantly suppressed neoplastic cell transformation by inhibiting the kinase activity of the EGF receptor (EGFR). The activation of EGFR by EGF was suppressed by MARC and MPML treatment in EGFR(+/+) cells, but not in EGFR(-/-) cells. In addition, MARC and MPML inhibited EGF-induced cell proliferation in EGFR-expressing murine embryonic fibroblasts (EGFR(+/+)). These results strongly indicate that EGFR targeting by MARC and MPML may be a good strategy for chemopreventive or chemotherapeutic applications.

The Changing Landscape of Early Childhood Education: Implications for Policy and Practice

ERIC Educational Resources Information Center

Haslip, Michael J.; Gullo, Dominic F.

2018-01-01

Early childhood education is changing rapidly due to the dynamic nature of positive and negative trends affecting the profession. In this article, the changing landscape of early childhood education is discussed and analyzed. Both the positive and negative forces contributing to the changing landscape are examined. The focus of this discussion…

Combined application of optical methods to increase the information content of optical coherent tomography in diagnostics of neoplastic processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuranov, R V; Sapozhnikova, V V; Shakhova, N M

2002-11-30

A combined application of optical methods [optical coherent tomography (OCT), cross-polarisation optical coherent tomography, and fluorescence spectroscopy] is proposed for obtaining information on morphological and biochemical changes occurring in tissues in norm and pathology. It is shown that neoplastic and scar changes in esophagus can be distinguished using a combination of polarisation and standard OCT due to the difference between the depolarising properties of the tissues caused by the structural properties of collagenic fibres in stroma. It is shown that OCT combined with fluorescence spectroscopy with the use of 5-aminolevulinic acid is promising for determining the boundaries of carcinoma ofmore » the uterine cervix and vulva. It is found that the tumour boundary detected by optical methods coincides with the morphological boundary and extends beyond colposcopically determined boundary by about 2 mm. (laser biology and medicine)« less

12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early involvement...

Early in-session cognitive-emotional problem-solving predicts 12-month outcomes in depression with personality disorder.

PubMed

McCarthy, Kye L; Mergenthaler, Erhard; Grenyer, Brin F S

2014-01-01

Therapist-patient verbalizations reveal complex cognitive-emotional linguistic data. How these variables contribute to change requires further research. Emotional-cognitive text analysis using the Ulm cycles model software was applied to transcripts of the third session of psychotherapy for 20 patients with depression and personality disorder. Results showed that connecting cycle sequences of problem-solving in the third hour predicted 12-month clinical outcomes. Therapist-patient dyads most improved spent significantly more time early in session in connecting cycles, whilst the least improved moved into connecting cycles late in session. For this particular sample, it was clear that positive emotional problem-solving in therapy was beneficial.

Correlation between ECG changes and early left ventricular remodeling in preadolescent footballers.

PubMed

Zdravkovic, M; Milovanovic, B; Hinic, S; Soldatovic, I; Durmic, T; Koracevic, G; Prijic, S; Markovic, O; Filipovic, B; Lovic, D

2017-03-01

The aim of this study was to assess the early electrocardiogram (ECG) changes induced by physical training in preadolescent elite footballers. This study included 94 preadolescent highly trained male footballers (FG) competing in Serbian Football League (minimum of 7 training hours/week) and 47 age-matched healthy male controls (less than 2 training hours/week) (CG). They were screened by ECG and echocardiography at a tertiary referral cardio center. Sokolow-Lyon index was used as a voltage electrocardiographic criterion for left ventricular hypertrophy diagnosis. Characteristic ECG intervals and voltage were compared and reference range was given for preadolescent footballers. Highly significant differences between FG and CG were registered in all ECG parameters: P-wave voltage (p < 0.001), S-wave (V1 or V2 lead) voltage (p < 0.001), R-wave (V5 and V6 lead) voltage (p < 0.001), ECG sum of S V 1-2  + R V 5-6 (p < 0.001), T-wave voltage (p < 0.001), QRS complex duration (p < 0.001), T-wave duration (p < 0.001), QTc interval duration (p < 0.001), and R/T ratio (p < 0.001). No differences were found in PQ interval duration between these two groups (p > 0.05). During 6-year follow-up period, there was no adverse cardiac event in these footballers. None of them expressed pathological ECG changes. Benign ECG changes are presented in the early stage of athlete's heart remodeling, but they are not related to pathological ECG changes and they should be regarded as ECG pattern of LV remodeling.

Hepcidin plasma levels are not associated with changes in haemoglobin in early rheumatoid arthritis patients.

PubMed

Østgård, R D; Glerup, H; Jurik, A G; Kragstrup, T W; Stengaard-Pedersen, K; Hetland, M L; Hørslev-Petersen, K; Junker, P; Deleuran, B W

2017-11-01

A reduction in haemoglobin level is a frequent complication among rheumatoid arthritis (RA) patients. Hepcidin has been linked to disturbed erythropoiesis. The objective of this study was to investigate the longitudinal changes in hepcidin in patients with early RA. Hepcidin plasma concentrations were measured by enzyme-linked immunosorbent assay in patients with early RA (n = 80) and healthy volunteers (HV, n = 40). Haemoglobin and other iron-related proteins were also measured. At baseline, all patients had active disease and were treatment naïve. Patients were treated with disease-modifying anti-rheumatic drugs (DMARDs) and with additional adalimumab (ADA, n = 42) or placebo (PLA, n = 38) during 52 weeks, using a treat-to-target strategy, aiming for a 28-joint Disease Activity Score (DAS28) < 3.2. At baseline, hepcidin levels [median (interquartile range)] were 9.7 ng/mL (5.2-19.4 ng/mL) in DMARD + ADA and 11.3 ng/mL (5.9-19.1 ng/mL) in DMARD + PLA. Both were significantly higher than seen in HV (6.0 ng/mL (3.3-9.3 ng/mL) (p < 0.001). After 12 months, both treatment regimens resulted in normalization of hepcidin. DAS28 correlated with hepcidin at baseline (r = 0.48, p < 0.001). No correlation was observed between levels of haemoglobin and hepcidin at baseline or during the 52 week follow-up. No change in haemoglobin levels was seen as a function of hepcidin changes. In a mixed statistical model, no single factor was connected with the regulation of haemoglobin in early RA. The changes in hepcidin were not associated with changes in haemoglobin levels. Thus, hepcidin could not be used as a prognostic marker in patients with early RA.

Angiogenesis and phenotypic alteration of alveolar capillary endothelium in areas of neoplastic cell spread in primary lung adenocarcinoma.

PubMed

Jin, E; Ghazizadeh, M; Fujiwara, M; Nagashima, M; Shimizu, H; Ohaki, Y; Arai, S; Gomibuchi, M; Takemura, T; Kawanami, O

2001-09-01

Normal alveolar capillary endothelium is quiescent in nature and displays anticoagulant thrombomodulin (TM) on its surface. The cytoplasms of these endothelial cells are ultrastructurally non-fenestrated type, and they barely express von Willebrand factor (vWf). Alveolar fibrosis is accompanied by a capillary endothelium reactive for vWf, and a loss of TM expression. In primary lung adenocarcinoma, neovascularization occurs in association with alveolar fibrosis. In order to study basic factors related to angiogenesis and phenotypic changes of the capillaries located in tumor-bearing alveolar walls, we examined 37 primary lung adenocarcinomas with electron microscopy and confocal laser scanning microscopy with antibodies for TM, vWf, vascular endothelial growth factor (VEGF), and its receptors (KDR and Flt-1), and proliferating markers (Ki-67/proliferating cell nuclear antigen). Tissues microdissected specifically from alveolar walls were used for reverse transcription-polymerase chain reaction (RT-PCR) to assess expressions of mRNA isoforms of VEGF and its receptors. New capillary branching was found by ultrastructural study in the alveolar walls in 12% of the patients. Nuclei of the capillary endothelial cells were reactive for proliferating cell markers. Endothelial fenestrae were developed in 65% of the patients, TM reactivity was lost in the alveolar capillaries, and their cell cytoplasms obtained a reactivity for vWf through a transitional mosaic-like distribution pattern of both antigens. Besides cytoplasmic VEGF expression in neoplastic cells, tumor-bearing alveolar walls showed significant expression of mRNA of VEGF165 and KDR. These findings imply that angiogenesis and phenotypic changes of the alveolar capillaries are closely related to a higher expression of tumor-associated VEGF165 and of KDR in the alveolar walls in primary lung adenocarcinoma.

A Sustainable Early Warning System for Climate Change Impacts on Water Quality Management

NASA Astrophysics Data System (ADS)

Lee, T.; Tung, C.; Chung, N.

2007-12-01

In this era of rapid social and technological change leading to interesting life complexity and environmental displacement, both positive and negative effects among ecosystems call for a balance in which there are impacts by climate changes. Early warning systems for climate change impacts are necessary in order to allow society as a whole to properly and usefully assimilate the masses of new information and knowledge. Therefore, our research addresses to build up a sustainable early warning mechanism. The main goal is to mitigate the cumulative impacts on the environment of climate change and enhance adaptive capacities. An effective early warning system has been proven for protection. However, there is a problem that estimate future climate changes would be faced with high uncertainty. In general, take estimations for climate change impacts would use the data from General Circulation Models and take the analysis as the Intergovernmental Panel on Climate Change declared. We follow the course of the method for analyzing climate change impacts and attempt to accomplish the sustainable early warning system for water quality management. Climate changes impact not only on individual situation but on short-term variation and long-term gradually changes. This kind characteristic should adopt the suitable warning system for long-term formulation and short- term operation. To continue the on-going research of the long-term early warning system for climate change impacts on water quality management, the short-term early warning system is established by using local observation data for reappraising the warning issue. The combination of long-term and short-term system can provide more circumstantial details. In Taiwan, a number of studies have revealed that climate change impacts on water quality, especially in arid period, the concentration of biological oxygen demand may turn into worse. Rapid population growth would also inflict injury on its assimilative capacity to

CBT for eating disorders: The impact of early changes in eating pathology on later changes in personality pathology, anxiety and depression.

PubMed

Turner, Hannah; Marshall, Emily; Wood, Francesca; Stopa, Lusia; Waller, Glenn

2016-02-01

Whilst studies have consistently identified early symptom reduction as an important predictor of treatment outcome, the impact of early change on common comorbid features has not been investigated. This study of CBT for eating disorders explored patterns of early change in eating pathology and longer-term change in personality pathology, anxiety and depression. It also explored the impact of early change in eating pathology on overall change in personality pathology, anxiety and depression. Participants were 179 adults diagnosed with eating disorders who were offered a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment and following the 6th session. They also completed measures of personality disorder cognitions, anxiety and depression at the start and end of treatment. There were significant changes in eating pathology over the first six sessions of treatment. Significant improvements were also seen in personality disorder pathology, anxiety and depression by the end of therapy. Effect sizes were medium to large for both completer and intention to treat analyses. Early changes in eating pathology were associated with later changes in common comorbid features, with early reduction in restraint being a key predictor. These findings demonstrate that early symptom change can be achieved in CBT for eating disorders when delivered in routine clinical practice. Such change has long-term benefits that go beyond the domain of eating pathology, enhancing change in personality pathology, anxiety and depression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early changes in somatosensory function in spinal pain: protocol for a systematic review

PubMed Central

2013-01-01

Background Back and neck pain are common conditions that have a high burden of disease. Changes in somatosensory function in the periphery, the spinal cord and the brain have been well documented at the time when these conditions have become chronic. It is unknown, however, how early these changes occur, what the timecourse is of sensory dysfunction and what the specific nature of these changes are in the first 12 weeks after onset of pain. In this paper, we describe the protocol for a systematic review of the literature on somatosensory dysfunction in the first 12 weeks after pain onset. Methods and design We will conduct a comprehensive search for articles indexed in the databases Ovid MEDLINE, Ovid Embase, Ovid PsycINFO and Cochrane Central Register of Controlled Trial (CENTRAL) from their inception to August 2013 that report on any aspect of somatosensory function in acute or subacute neck or back pain. Two independent reviewers will screen studies for eligibility, assess risk of bias and extract relevant data. Results will be tabulated and a narrative synthesis of the results conducted. Discussion Currently, there is a gap in our knowledge about the timing of somatosensory changes in back and neck pain. The systematic review outlined in this protocol aims to address this knowledge gap and inform developments in diagnostic tools and pain mechanism-based treatments. Trial Registration Our protocol has been registered on PROSPERO, CRD42013005113. PMID:24088219

Dual modality imaging of a novel rat model of ovarian carcinogenesis

NASA Astrophysics Data System (ADS)

Kanter, Elizabeth; Walker, Ross; Marion, Sam; Brewer, Molly A.; Hoyer, Patricia B.; Barton, Jennifer K.

2006-07-01

Ovarian cancer is the fifth leading cause of cancer death in women, in part because of the limited knowledge about early stage disease. We develop a novel rat model of ovarian cancer and perform a pilot study to examine the harvested ovaries with complementary optical imaging modalities. Rats are exposed to repeated daily dosing (20 days) with 4-vinylcyclohexene diepoxide (VCD) to cause early ovarian failure (model for postmenopause), and ovaries are directly exposed to 7,12-dimethylbenz(a)anthracene (DMBA) to cause abnormal ovarian proliferation and neoplasia. Harvested ovaries are examined with optical coherence tomography (OCT) and light-induced fluorescence (LIF) at one, three, and five months post-DMBA treatment. VCD causes complete ovarian follicle depletion within 8 months after onset of dosing. DMBA induces abnormal size, cysts, and neoplastic changes. OCT successfully visualizes normal and abnormal structures (e.g., cysts, bursa, follicular remnant degeneration) and the LIF spectra show statistically significant changes in the ratio of average emission intensity at 390:450 nm between VCD-treated ovaries and both normal cycling and neoplastic DMBA-treated ovaries. Overall, this pilot study demonstrates the feasibility of both the novel animal model for ovarian cancer and the ability of optical imaging techniques to visualize ovarian function and health.

Neoplastic transformation of human thyroid epithelial cells by ionizing radiation

NASA Astrophysics Data System (ADS)

Herceg, Zdenko

Neoplastic transformation of human thyroid epithelial cells has been investigated following exposure to ionizing radiation in vitro. The effects of radiation type, irradiation regime, and postirradiation passaging were examined using a human thyroid epithelial cell line, designated HToriS, which was previously immortalized with SV40 genome. Exponentially growing HToriS cells were irradiated with graded doses of 137 Cs gamma- and 238pu alpha-irradiation. Cells were irradiated with either a single or multiple doses of 0.5, 1, 2, 3, or 4 Gy gamma-radiation, or single doses of 0.125, 0.25, 0.5, 1, or 1.5 Gy gamma-radiation. Following passaging, the cells were transplanted into the athymic nude mice, and the animals were screened for tumour formation. Statistically significant increases in tumour incidence were obtained with both gamma- and alpha-irradiation and with both single and multiple irradiation regimes as compared with the un-irradiated group. Regardless of radiation type and or radiation regime there appears to be a trend, with increasing doses of radiation, in which tumour incidence increases and reaches a maximum, after which the tumour incidence decreases. Tumours were characterized by histopathological examination as undifferentiated carcinomas. Investigation of expression time following irradiation demonstrated that post-irradiation passaging, generally regarded as a critical step for expression of radiation-induced DNA damage, was not a prerequisite for the neoplastic conversion of irradiated cells with this system. Cell lines were established from the tumours and their identification and characterization carried out. All cell lines established were determined to be derived from the parent HTori3 cells by DNA fingerprinting, karyotype analysis, cytokeratin staining, and SV40 large T-antigen staining. Tumorigenicity of the cell lines was confirmed by retransplantation. Comparison of the morphology in vitro showed that the tumour cell lines retained the

Early changes in somatosensory function in spinal pain: a systematic review and meta-analysis.

PubMed

Marcuzzi, Anna; Dean, Catherine M; Wrigley, Paul J; Hush, Julia M

2015-02-01

Alterations in sensory processing have been demonstrated in chronic low back and neck pain. However, it has not been yet systematically summarized how early these changes occur in spinal pain. This systematic review examines the available literature measuring somatosensory function in acute (<6 weeks) and subacute (6-12 weeks) spinal pain. The protocol for this review has been registered on the International Prospective Register of Systematic Reviews (PROSPERO). An electronic search of 4 databases was conducted to retrieve studies assessing somatosensory function by quantitative sensory testing in adults with spinal pain of up to 12 weeks duration. Two reviewers independently screened the studies and assessed the risk of bias. Studies were grouped according to spinal pain condition (whiplash injury, idiopathic neck pain, and nonspecific low back pain), and, where possible, meta-analyses were performed for comparable results. Fifteen studies were included. Sources of bias included lack of assessor blinding, unclear sampling methods, and lack of control for confounders. We found that: (1) there is consistent evidence for thermal and widespread mechanical pain hypersensitivity in the acute stage of whiplash, (2) there is no evidence for pain hypersensitivity in the acute and subacute stage of idiopathic neck pain, although the body of evidence is small, and (3) hyperalgesia and spinal cord hyperexcitability have been detected in early stages of nonspecific low back pain, although evidence about widespread effects are conflicting. Future longitudinal research using multiple sensory modalities and standardized testing may reveal the involvement of somatosensory changes in the development and maintenance of chronic pain.

Vitamin B12 intake and status in early pregnancy among urban South Indian women

PubMed Central

Samuel, Tinu Mary; Duggan, Christopher; Thomas, Tinku; Bosch, Ronald; Rajendran, Ramya; Virtanen, Suvi M; Srinivasan, Krishnamachari; Kurpad, Anura V

2015-01-01

Aim To evaluate the vitamin B12 status of South Indian women in early pregnancy and its relationship with sociodemographic, anthropometry and dietary intake. Methods Cross-sectional study among 366 pregnant urban South Indian women ≤14 weeks of gestation with outcome variables defined as low vitamin B12 blood concentration (<150 pmol/L) and impaired vitamin B12 status [low vitamin B12 plus elevated methylmalonic acid (MMA) >0.26 μmol/L)]. Results Low plasma vitamin B12 concentration was observed in 51.1% of the women, while 42.4% had impaired B12 status. Elevated MMA, elevated homocysteine ( >10 μmol/L) and low erythrocyte folate (<283 nmol/L) was observed among 75.8%, 43.3% and 22.2% of women, respectively. The median (25th, 75th percentile) dietary intake of vitamin B12 was 1.25 (0.86, 1.96) μg/day. Lower maternal body weight was associated with higher vitamin B12 concentration [prevalence ratios (PR) (95% CI) 0.57 (0.39, 0.84)). The predictors of impaired vitamin B12 status were non-use of yoghurt [PR (95%CI) 1.63 (1.03, 2.58)], non-use of fish [PR (95% CI) 1.32 (1.01, 1.71)] and primiparity [PR (95% CI) 1.41 (1.05, 1.90)]. Conclusion A high prevalence of vitamin B12 deficiency in early pregnancy among urban South Indian women was related to primiparity and to a low consumption of yoghurt and fish. PMID:23344013

Early Change in Stroke Size Performs Best in Predicting Response to Therapy.

PubMed

Simpkins, Alexis Nétis; Dias, Christian; Norato, Gina; Kim, Eunhee; Leigh, Richard

2017-01-01

Reliable imaging biomarkers of response to therapy in acute stroke are needed. The final infarct volume and percent of early reperfusion have been used for this purpose. Early fluctuation in stroke size is a recognized phenomenon, but its utility as a biomarker for response to therapy has not been established. This study examined the clinical relevance of early change in stroke volume and compared it with the final infarct volume and percent of early reperfusion in identifying early neurologic improvement (ENI). Acute stroke patients, enrolled between 2013 and 2014 with serial magnetic resonance imaging (MRI) scans (pretreatment baseline, 2 h post, and 24 h post), who received thrombolysis were included in the analysis. Early change in stroke volume, infarct volume at 24 h on diffusion, and percent of early reperfusion were calculated from the baseline and 2 h MRI scans were compared. ENI was defined as ≥4 point decrease in National Institutes of Health Stroke Scales within 24 h. Logistic regression models and receiver operator characteristics analysis were used to compare the efficacy of 3 imaging biomarkers. Serial MRIs of 58 acute stroke patients were analyzed. Early change in stroke volume was significantly associated with ENI by logistic regression analysis (OR 0.93, p = 0.048) and remained significant after controlling for stroke size and severity (OR 0.90, p = 0.032). Thus, for every 1 mL increase in stroke volume, there was a 10% decrease in the odds of ENI, while for every 1 mL decrease in stroke volume, there was a 10% increase in the odds of ENI. Neither infarct volume at 24 h nor percent of early reperfusion were significantly associated with ENI by logistic regression. Receiver-operator characteristic analysis identified early change in stroke volume as the only biomarker of the 3 that performed significantly different than chance (p = 0.03). Early fluctuations in stroke size may represent a more reliable biomarker for response to therapy than the

Epigenetic changes in solid and hematopoietic tumors.

PubMed

Toyota, Minoru; Issa, Jean-Pierre J

2005-10-01

There are three connected molecular mechanisms of epigenetic cellular memory in mammalian cells: DNA methylation, histone modifications, and RNA interference. The first two have now been firmly linked to neoplastic transformation. Hypermethylation of CpG-rich promoters triggers local histone code modifications resulting in a cellular camouflage mechanism that sequesters gene promoters away from transcription factors and results in stable silencing. This normally restricted mechanism is ubiquitously used in cancer to silence hundreds of genes, among which some critically contribute to the neoplastic phenotype. Virtually every pathway important to cancer formation is affected by this process. Methylation profiling of human cancers reveals tissue-specific epigenetic signatures, as well as tumor-specific signatures, reflecting in particular the presence of epigenetic instability in a subset of cancers affected by the CpG island methylator phenotype. Generally, methylation patterns can be traced to a tissue-specific, proliferation-dependent accumulation of aberrant promoter methylation in aging tissues, a process that can be accelerated by chronic inflammation and less well-defined mechanisms including, possibly, diet and genetic predisposition. The epigenetic machinery can also be altered in cancer by specific lesions in epigenetic effector genes, or by aberrant recruitment of these genes by mutant transcription factors and coactivators. Epigenetic patterns are proving clinically useful in human oncology via risk assessment, early detection, and prognostic classification. Pharmacologic manipulation of these patterns-epigenetic therapy-is also poised to change the way we treat cancer in the clinic.

The FDA approved PI3K inhibitor GDC-0941 enhances in vitro the anti-neoplastic efficacy of Axitinib against c-myc-amplified high-risk medulloblastoma.

PubMed

Ehrhardt, Michael; Craveiro, Rogerio B; Velz, Julia; Olschewski, Martin; Casati, Anna; Schönberger, Stefan; Pietsch, Torsten; Dilloo, Dagmar

2018-04-01

Aberrant receptor kinase signalling and tumour neovascularization are hallmarks of medulloblastoma development and are both considered valuable therapeutic targets. In addition to VEGFR1/2, expression of PDGFR α/β in particular has been documented as characteristic of metastatic disease correlating with poor prognosis. Therefore, we have been suggested that the clinically approved multi-kinase angiogenesis inhibitor Axitinib, which specifically targets these kinases, might constitute a promising option for medulloblastoma treatment. Indeed, our results delineate anti-neoplastic activity of Axitinib in medulloblastoma cell lines modelling the most aggressive c-myc-amplified Non-WNT/Non-SHH and SHH-TP53-mutated tumours. Exposure of medulloblastoma cell lines to Axitinib results in marked inhibition of proliferation and profound induction of cell death. The differential efficacy of Axitinib is in line with target expression of medulloblastoma cells identifying VEGFR 1/2, PDGFR α/β and c-kit as potential markers for drug application. The high specificity of Axitinib and the consequential low impact on the haematopoietic and immune system render this drug ideal multi-modal treatment approaches. In this context, we demonstrate that the clinically available PI3K inhibitor GDC-0941 enhances the anti-neoplastic efficacy of Axitinib against c-myc-amplified medulloblastoma. Our findings provide a rational to further evaluate Axitinib alone and in combination with other therapeutic agents for the treatment of most aggressive medulloblastoma subtypes. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Optical redox ratio differentiates early tissue transformations in DMBA-induced hamster oral carcinogenesis based on autofluorescence spectroscopy coupled with multivariate analysis

NASA Astrophysics Data System (ADS)

Sethupathi, R.; Gurushankar, K.; Krishnakumar, N.

2016-11-01

Fluorescence intensity measurements have the potential to facilitate the diagnoses of many pathological conditions. The changes in fluorescence intensity may be influenced by factors such as tissue architectures, endogenous fluorophores, cellular metabolism and light penetration depth in tissue. Two of the most diagnostically important endogenous fluorophores are reduced nicotinamide dinucleotide (NADH) and flavin adenine dinucleotide (FAD), which can be used to monitor dramatic metabolic changes in cells and tissues. The goal of this study is to investigate changes in the endogenous fluorophore emission and to quantify metabolic changes in the redox state of various tissue transformation conditions with respect to control tissues in dimethyl benz[a] anthracene (DMBA)-induced hamster oral carcinogenesis for measuring emission spectrum at 320 nm excitation. In the present study, collagen, NADH and FAD emission of well-differentiated squamous cell carcinoma (WDSCC) showed decreased intensity at ~385 nm, ~450 nm and ~520 nm compared to hyperplasia, dysplasia and control tissues. Furthermore, a significant decrease in the optical redox ratio is observed in WDSCC tissues, which indicates an increased metabolic activity compared to the control tissues. Moreover, the principal component linear discriminant analysis (PC-LDA) algorithm together with the leave-one-out cross-validation (LOOCV) method yield an overall diagnostic sensitivity of 77.7% and a specificity of 88.8% in the classification of control, hyperplasia, dysplasia and WDSCC tissues, respectively. The results from this study demonstrated that fluorescence-based tissue analysis combined with PC-LDA has tremendous potential for the effective discrimination of control from neoplastic tissues; furthermore it also detects early neoplastic changes prior to definite morphologic alteration.

Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC.

PubMed

Scarpa, Marco; Scarpa, Melania; Castagliuolo, Ignazio; Erroi, Francesca; Kotsafti, Andromachi; Basato, Silvia; Brun, Paola; D'Incà, Renata; Rugge, Massimo; Angriman, Imerio; Castoro, Carlo

2016-03-01

BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance.

Early evidence (ca. 12,000 B.P.) for feasting at a burial cave in Israel

PubMed Central

Munro, Natalie D.; Grosman, Leore

2010-01-01

Feasting is one of humanity's most universal and unique social behaviors. Although evidence for feasting is common in the early agricultural societies of the Neolithic, evidence in pre-Neolithic contexts is more elusive. We found clear evidence for feasting on wild cattle and tortoises at Hilazon Tachtit cave, a Late Epipaleolithic (12,000 calibrated years B.P.) burial site in Israel. This includes unusually high densities of butchered tortoise and wild cattle remains in two structures, the unique location of the feasting activity in a burial cave, and the manufacture of two structures for burial and related feasting activities. The results indicate that community members coalesced at Hilazon to engage in special rituals to commemorate the burial of the dead and that feasts were central elements in these important events. Feasts likely served important roles in the negotiation and solidification of social relationships, the integration of communities, and the mitigation of scalar stress. These and other social changes in the Natufian period mark significant changes in human social complexity that continued into the Neolithic period. Together, social and economic change signal the very beginning of the agricultural transition. PMID:20805510

12 CFR 714.8 - Are the early payment provisions, or interest rate provisions, applicable in leasing arrangements?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Are the early payment provisions, or interest... CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS LEASING § 714.8 Are the early payment provisions, or interest rate provisions, applicable in leasing arrangements? You are not subject to the early...

Motivation, Work Satisfaction, and Teacher Change among Early Childhood Teachers

ERIC Educational Resources Information Center

Wagner, Brigid Daly; French, Lucia

2010-01-01

This study tests the explanatory power of Deci and Ryan's (1985) self-determination theory as a framework for describing how interactions between early childhood teachers and the systems within which their work is embedded influence motivation for professional growth and change in teaching practice. Fifty-four early childhood teachers and teacher…

Reduced Pms2 expression in non-neoplastic flat mucosa from patients with colon cancer correlates with reduced apoptosis competence.

PubMed

Bernstein, Harris; Prasad, Anil; Holubec, Hana; Bernstein, Carol; Payne, Claire M; Ramsey, Lois; Dvorakova, Katerina; Wilson, Megan; Warneke, James A; Garewal, Harinder

2006-06-01

Pms2 protein is a component of the DNA mismatch repair complex responsible both for post-replication correction of DNA nucleotide mispairs and for early steps in apoptosis. Germline mutations in DNA mismatch repair genes give rise to hereditary non-polyposis colon cancer, which accounts for about 4% of colon cancers. However, little is known about the expression of mismatch repair proteins in relation to sporadic colon cancer, which accounts for the great majority of colon cancers. Multiple samples were taken from the non-neoplastic flat mucosa of colon resections from patients with no colonic neoplasia, a tubulovillous adenoma, or an adenocarcinoma. Expression of Pms2 was assessed using semiquantitative immunohistochemistry. Apoptosis was assessed in polychrome-stained epoxy sections using morphologic criteria. Samples from patients without colonic neoplasia had moderate to strong staining for Pms2 in cell nuclei at the base of crypts, while samples from 2 of the 3 colons with a tubulovillous adenoma, and from 6 of the 10 colons with adenocarcinomas, showed reduced Pms2 expression. Samples from patients with an adenocarcinoma that had reduced Pms2 expression also exhibited reduced apoptosis capability in nearby tissue samples, evidenced when this paired tissue was stressed ex vivo with bile acid. Reduced Pms2 expression in the colonic mucosa may be an early step in progression to colon cancer. This reduction may cause decreased mismatch repair, increased genetic instability, and/or reduced apoptotic capability. Immunohistochemical determination of reduced Pms2 expression, upon further testing, may prove to be a promising early biomarker of risk of progression to malignancy.

Immunological cross-reactivity between acid extracts of myelin, liver and neoplastic tissues: studies in immunized guinea-pigs.

PubMed Central

Flavell, D. J.; Goepel, J.; Wilson, A. P.; Potter, C. W.

1979-01-01

Groups of 4 guinea-pigs were immunized with acid extracts prepared from bovine myelin (EF), normal human liver tissue and malignant or benign neoplastic tissues in Freund's complete adjuvant (FCA1. The animals were weighed daily and examined for clinical signs of experimental allergic encephalomyelitis (EAE). All the animals immunized with EF developed clinical symptoms of EAE within 21 days of the initial immunization, whilst some of the animals immunized with certain tumour extracts developed symptoms which closely resembled those of EAE. Control animals immunized with FCA only remained asymptomatic. Cellular immunity to the various extracts in immunized animals was assessed 20 days after immunization by i.d. skin testing, and upon killing at Day 21 with the direct peritoneal-exudate macrophage migration inhibition (MMI) test. Brains and spinal cords were removed at killing, fixed in formalin and processed for histological examination. I.d. skin testing was shown to be most consistent in demonstrating positive delayed hypersensitivity, whilst the MMI test frequently gave negative results in the presence of pronounced skin responses to specific extracts. Thus it was shown that 3/4 animals immunized with basic proteins extracted from an adenocarcinoma of the lung or related hepatic metastases, and 1/2 animals immunized with an extract of a carcinoma of the breast, gave intense erythema and induration responses 5 mm in diameter 24 h after i.d. challenge with EF. No such response was obtained in animals immunized with basic proteins extracted from normal human liver, any of the other neoplastic tissues, or in control animals immunized with FCA only. Examination of brains and spinal cords from animals immunized with EF revealed dense infiltration by mononuclear cells in the ependyma and choroid plexus of levels in the spinal cord. Examination of brains and spinal cords from animals immunized with the lung-tumour extract or related hepatic metastases which showed

Are Early Childhood Disparities Narrowing? The Changing Nature of Early Childhood and Its Link to Narrowing School-Entry Achievement Gaps

ERIC Educational Resources Information Center

Bassok, Daphna; Finch, Jenna; Lee, RaeHyuck; Reardon, Sean F.; Waldfogel, Jane

2016-01-01

To date, no studies have documented how much early childhood experiences have changed over time. In the current study, researchers use two large, nationally representative datasets of kindergarten entrants to document the following: (1) How have children's early childhood experiences changed between 1998 and 2010?; (2) To what extent have…

Discrimination of benign and neoplastic mucosa with a high-resolution microendoscope (HRME) in head and neck cancer.

PubMed

Vila, Peter M; Park, Chan W; Pierce, Mark C; Goldstein, Gregg H; Levy, Lauren; Gurudutt, Vivek V; Polydorides, Alexandros D; Godbold, James H; Teng, Marita S; Genden, Eric M; Miles, Brett A; Anandasabapathy, Sharmila; Gillenwater, Ann M; Richards-Kortum, Rebecca; Sikora, Andrew G

2012-10-01

The efficacy of ablative surgery for head and neck squamous cell carcinoma (HNSCC) depends critically on obtaining negative margins. Although intraoperative "frozen section" analysis of margins is a valuable adjunct, it is expensive, time-consuming, and highly dependent on pathologist expertise. Optical imaging has potential to improve the accuracy of margins by identifying cancerous tissue in real time. Our goal was to determine the accuracy and inter-rater reliability of head and neck cancer specialists using high-resolution microendoscopic (HRME) images to discriminate between cancerous and benign mucosa. Thirty-eight patients diagnosed with head and neck squamous cell carcinoma (HNSCC) were enrolled in this single-center study. HRME was used to image each specimen after application of proflavine, with concurrent standard histopathologic analysis. Images were evaluated for quality control, and a training set containing representative images of benign and neoplastic tissue was assembled. After viewing training images, seven head and neck cancer specialists with no previous HRME experience reviewed 36 test images and were asked to classify each. The mean accuracy of all reviewers in correctly diagnosing neoplastic mucosa was 97% (95% confidence interval (CI), 94-99%). The mean sensitivity and specificity were 98% (97-100%) and 92% (87-98%), respectively. The Fleiss kappa statistic for inter-rater reliability was 0.84 (0.77-0.91). Medical professionals can be quickly trained to use HRME to discriminate between benign and neoplastic mucosa in the head and neck. With further development, the HRME shows promise as a method of real-time margin determination at the point of care.

Discrimination of Benign and Neoplastic Mucosa with a High-Resolution Microendoscope (HRME) in Head and Neck Cancer

PubMed Central

Vila, Peter M.; Park, Chan W.; Pierce, Mark C.; Goldstein, Gregg H.; Levy, Lauren; Gurudutt, Vivek V.; Polydorides, Alexandras D.; Godbold, James H.; Teng, Marita S.; Genden, Eric M.; Miles, Brett A.; Anandasabapathy, Sharmila; Gillenwater, Ann M.; Richards-Kortum, Rebecca; Sikora, Andrew G.

2012-01-01

Background The efficacy of ablative surgery for head and neck squamous cell carcinoma (HNSCC) depends critically on obtaining negative margins. While intraoperative "frozen section" analysis of margins is a valuable adjunct, it is expensive, time-consuming, and highly dependent on pathologist expertise. Optical imaging has potential to improve the accuracy of margins by identifying cancerous tissue in real time. Our aim was to determine the accuracy and inter-rater reliability of head and neck cancer specialists using high-resolution microendoscopic (HRME) images to discriminate between cancerous and benign mucosa. Methods Thirty-eight patients diagnosed with HNSCC were enrolled in this single-center study. HRME was used to image each specimen after application of proflavine, with concurrent standard histopathologic analysis. Images were evaluated for quality control, and a training set containing representative images of benign and neoplastic tissue was assembled. After viewing training images, seven head and neck cancer specialists with no prior HRME experience reviewed 37 test images and were asked to classify each. Results The mean accuracy of all reviewers in correctly diagnosing neoplastic mucosa was 97 percent (95% Cl = 94–99%). The mean sensitivity and specificity were 98 percent (97–100%) and 92 percent (87–98%), respectively. The Fleiss kappa statistic for inter-rater reliability was 0.84 (0.77–0.91). Conclusions Medical professionals can be quickly trained to use HRME to discriminate between benign and neoplastic mucosa in the head and neck. With further development, the HRME shows promise as a method of real-time margin determination at the point of care. PMID:22492225

Impact of Major Pulmonary Resections on Right Ventricular Function: Early Postoperative Changes.

PubMed

Elrakhawy, Hany M; Alassal, Mohamed A; Shaalan, Ayman M; Awad, Ahmed A; Sayed, Sameh; Saffan, Mohammad M

2018-01-15

Right ventricular (RV) dysfunction after pulmonary resection in the early postoperative period is documented by reduced RV ejection fraction and increased RV end-diastolic volume index. Supraventricular arrhythmia, particularly atrial fibrillation, is common after pulmonary resection. RV assessment can be done by non-invasive methods and/or invasive approaches such as right cardiac catheterization. Incorporation of a rapid response thermistor to pulmonary artery catheter permits continuous measurements of cardiac output, right ventricular ejection fraction, and right ventricular end-diastolic volume. It can also be used for right atrial and right ventricular pacing, and for measuring right-sided pressures, including pulmonary capillary wedge pressure. This study included 178 patients who underwent major pulmonary resections, 36 who underwent pneumonectomy assigned as group (I) and 142 who underwent lobectomy assigned as group (II). The study was conducted at the cardiothoracic surgery department of Benha University hospital in Egypt; patients enrolled were operated on from February 2012 to February 2016. A rapid response thermistor pulmonary artery catheter was inserted via the right internal jugular vein. Preoperatively the following was recorded: central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac output, right ventricular ejection fraction and volumes. The same parameters were collected in fixed time intervals after 3 hours, 6 hours, 12 hours, 24 hours, and 48 hours postoperatively. For group (I): There were no statistically significant changes between the preoperative and postoperative records in the central venous pressure and mean arterial pressure; there were no statistically significant changes in the preoperative and 12, 24, and 48 hour postoperative records for cardiac index; 3 and 6 hours postoperative showed significant changes. There were statistically significant changes between the preoperative and

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh

2016-01-01

Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed themore » dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and

Radiotherapy-induced Early ECG Changes and Their Comparison with Echocardiography in Patients with Early-stage Breast Cancer.

PubMed

Tuohinen, Suvi Sirkku; Keski-Pukkila, Konsta; Skyttä, Tanja; Huhtala, Heini; Virtanen, Vesa; Kellokumpu-Lehtinen, Pirkko-Liisa; Raatikainen, Pekka; Nikus, Kjell

2018-04-01

Early electrocardiogram (ECG) changes after breast cancer radiotherapy (RT) have been reported, but their characteristics and associated factors are largely unknown. This study aimed to explore early RT-induced ECG changes and to compare them with echocardiography changes. Sixty eligible patients with chemotherapy-naïve left-sided and 20 with right-sided breast cancer were evaluated with echocardiography, blood samples and ECG before and after RT. RT-induced ECG changes in the anterior leads. T-Wave changes were most frequent. T-Wave decline was associated independently with patient age (β=-0.245, p=0.005), mean heart radiation dose (β=1.252, p=0.001) and global systolic strain rate change (β=7.943, p=0.002). T-Wave inversion was associated independently with mean heart radiation dose (β=0.143, p<0.001), global longitudinal strain change (β=0.053, p=0.017) and posterior calibrated integrated backscatter (β=-0.022, p=0.049). RT-induced ECG changes were prevalent and associated with functional and structural changes in echocardiography. ECG could be used for post-RT cardiac screening. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

MiR-137: an important player in neural development and neoplastic transformation

PubMed Central

Mahmoudi, E; Cairns, M J

2017-01-01

MicroRNAs (miRNAs) represent an important class of small regulatory RNAs that control gene expression posttranscriptionally by targeting mRNAs for degradation or translation inhibition. Early studies have revealed a complex role for miRNAs in major biological processes such as development, differentiation, growth and metabolism. MiR-137 in particular, has been of great interest due to its critical role in brain function and putative involvement in the etiology of both neuropsychiatric disorders and cancer. Several lines of evidence suggest that development, differentiation and maturation of the nervous system is strongly linked to the expression of miR-137 and its regulation of a large number of downstream target genes in various pathways. Dysregulation of this molecule has also been implicated in major mental illnesses through its position in a variant allele highly associated with schizophrenia in the largest mega genome-wide association studies. Interestingly, miR-137 has also been shown to act as a tumor suppressor, with numerous studies finding reduced expression in neoplasia including brain tumor. Restoration of miR-137 expression has also been shown to inhibit cell proliferation, migration and metastasis, and induce cell cycle arrest, differentiation and apoptosis. These properties of miR-137 propose its potential for prognosis, diagnosis and as a therapeutic target for treatment of several human neurological and neoplastic disorders. In this review, we provide details on the discovery, targets, function, regulation and disease involvement of miR-137 with a broad look at recent discovery in this area. PMID:27620842

12 CFR 1710.18 - Change of audit partner.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Change of audit partner. 1710.18 Section 1710.18 Banks and Banking OFFICE OF FEDERAL HOUSING ENTERPRISE OVERSIGHT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT SAFETY AND SOUNDNESS CORPORATE GOVERNANCE Corporate Practices and Procedures § 1710.18 Change of...

HPV genotype distribution and anomalous association of HPV33 to cervical neoplastic lesions in San Luis Potosí, Mexico.

PubMed

DelaRosa-Martínez, Raúl; Sánchez-Garza, Mireya; López-Revilla, Rubén

2016-01-01

The association of human papillomavirus (HPV) types to neoplastic lesions increase as a function of their oncogenicity and the duration of the infection since lesion severity progresses from low-grade to high-grade and cancer. In an outbreak, the prevalence of the HPV type involved would increase and the proportion of the associated low-grade lesions would predominate over severe lesions. In this study, the prevalence of HPV types and their association to neoplastic lesions was determined in women subjected to colposcopy in San Luis Potosí, Mexico. DNA from high-risk (HR) and low-risk (LR) HPV types was identified by E6 nested multiplex PCR in cervical scrapes from 700 women with normal cytology, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL) or invasive cervical cancer (CC). Overall HPV-DNA prevalence was 67.7 %, that of HR-HPV was 63.1 %, and that of LR-HPV was 21.3 %. The highest prevalence (78.2 %) occurred in the 15-24 year group, whereas that of single infections was 52 % and that of multiple infections (i.e., by 2-6 HPV types) was 48 %. The most prevalent HR types were HPV33 (33.1 %), HPV16 (16.6 %), HPV18 and HPV51 (6.7 % each). HR-HPV prevalence was 29.6 % in normal cytology, 26.7 % in ASCUS, 63.3 % in LSIL, 68.2 % in HSIL, and 90.5 % in CC. Three prevalence trends for HR-HPV types were found in neoplastic lesions of increasing severity: increasing (LSIL < HSIL < CC) for HPV16, HPV39, HPV18, HPV58, HPV31 and HPV35; asymptotic (LSIL < HSIL ≈ CC) for HPV51 and HPV68; U-shaped (LSIL < HSIL > CC) for HPV33. Two-thirds of the women subjected to colposcopy from 2007 to 2010 in San Luis Potosí have HPV infections which predominate in the 15-24 years group. Around half of the infections are by one viral type and the rest by 2-6 types. HPV33 is the most prevalent type, followed by HPV16. Overall HR

Early Self-Regulation, Early Self-Regulatory Change, and Their Longitudinal Relations to Adolescents' Academic, Health, and Mental Well-Being Outcomes.

PubMed

Howard, Steven J; Williams, Kate E

2018-05-16

To evaluate the extent to which early self-regulation and early changes in self-regulation are associated with adolescents' academic, health, and mental well-being outcomes. Data were collected from 1 of the cohorts in a large dual-cohort cross-sequential study of Australian children. This cohort consisted of a nationally representative data set of 4983 Australian children assessed at 4 to 5 years of age, who were followed longitudinally to 14 to 15 years of age. Using regression within a path analysis framework, we first sought to investigate associations of early self-regulation (at 4-5 years and 6-7 years of age) with a broad range of academic, health, and mental well-being outcomes in adolescence (at 14-15 years). We next investigated the extent to which an early change in self-regulation (from 4 to 7 years of age) predicted these adolescents' outcomes. Early self-regulation predicted the full range of adolescents' outcomes considered such that a 1-SD increase in self-regulation problems was associated with a 1.5- to 2.5-times greater risk of more-negative outcomes. An early positive change in self-regulation was associated with a reduced risk of these negative outcomes for 11 of the 13 outcomes considered. These results suggest the potential of early self-regulation interventions, in particular, in influencing long-term academic, health, and well-being trajectories.

IL-4 downregulates expression of the target receptor CD30 in neoplastic canine mast cells

PubMed Central

Bauer, K.; Hadzijusufovic, E.; Cerny-Reiterer, S.; Hoermann, G.; Reifinger, M.; Pirker, A.; Valent, P.; Willmann, M.

2018-01-01

CD30 is a novel therapeutic target in human mast cell (MC) neoplasms. In this ‘comparative oncology’ study, we examined CD30 expression and regulation in neoplastic canine MC using a panel of immunomodulatory cytokines [interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-13 and stem cell factor (SCF)] and the canine mastocytoma cell lines NI-1 and C2. Of all cytokines tested IL-4 was found to downregulate expression of CD30 in NI-1 and C2 cells. We also found that the CD30-targeting antibody-conjugate brentuximab vedotin induces growth inhibition and apoptosis in both MC lines. Next, we asked whether IL-4-induced downregulation of CD30 interferes with brentuximab vedotin-effects. Indeed, pre-incubation of NI-1 cells with IL-4 decreased responsiveness towards brentuximab vedotin. To overcome IL-4-mediated resistance, we applied drug combinations and found that brentuximab vedotin synergizes with the Kit-targeting drugs masitinib and PKC412 in inhibiting growth of NI-1 and C2 cells. In summary, CD30 is a new marker and IL-4-regulated target in neoplastic canine MC. PMID:27507155

IQ at age 12 following a history of institutional care: Findings from the Bucharest Early Intervention Project

PubMed Central

Almas, Alisa N.; Degnan, Kathryn A.; Nelson, Charles A.; Zeanah, Charles H.; Fox, Nathan A.

2016-01-01

Young children removed from institutions and placed into foster care or adoptive homes have been shown to experience significant gains in IQ relative to children who remain in institutions. Less is known about the long-term impact of severe early deprivation on development in late childhood. Data are presented from a follow-up of children at 12 years of age in the Bucharest Early Intervention Project, a randomized clinical trial of foster care for institutionally reared children. One hundred and seven of the original 136 children in the study were tested with the WISC IV. Results revealed continued benefit from the intervention through age 12, with 12-year-old children placed in foster care scoring significantly higher on full scale IQ compared to their peers who received prolonged institutional care. Longitudinal IQ data revealed two IQ profiles from early to late childhood. Attachment security emerged as a significant predictor of a profile of stable, typical IQ scores over time. We demonstrate the continued importance of foster care intervention and the negative effects of severe, early psychosocial deprivation on IQ into late childhood. PMID:27709994

IQ at age 12 following a history of institutional care: Findings from the Bucharest Early Intervention Project.

PubMed

Almas, Alisa N; Degnan, Kathryn A; Nelson, Charles A; Zeanah, Charles H; Fox, Nathan A

2016-11-01

Young children removed from institutions and placed into foster care or adoptive homes have been shown to experience significant gains in IQ relative to children who remain in institutions. Less is known about the long-term impact of severe early deprivation on development in late childhood. Data are presented from a follow-up of children at 12 years of age in the Bucharest Early Intervention Project, a randomized clinical trial of foster care for institutionally reared children. Of the original 136 children in the study, 107 were tested with the Wechsler Intelligence Scale for Children-IV. Results revealed continued benefit from the intervention through age 12, with 12-year-old children placed in foster care scoring significantly higher on full-scale IQ compared to their peers who received prolonged institutional care. Longitudinal IQ data revealed 2 IQ profiles from early to late childhood. Attachment security emerged as a significant predictor of a profile of stable, typical IQ scores over time. We demonstrate the continued importance of foster care intervention and the negative effects of severe, early psychosocial deprivation on IQ into late childhood. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

[Relationship between body weight status in early adulthood and body weight change to middle age and high-density lipoprotein cholesterol level in middle aged Chinese people].

PubMed

Zhao, L C; Zhou, L; Li, Y; Guo, M; Wu, Y F

2016-08-24

To explore the relationship between early adulthood weight status and body weight changes from early adulthood to middle age and high-density lipoprotein cholesterol (HDL-C) level. Data were obtained from China Multicenter Collaborative Study of Cardiovascular Epidemiology Study, which was conducted in 1998, 15 participants population samples aged from 35-59 years old from 12 provinces were selected by random cluster sampling. Approximately 1 000 men and women in each sample population were surveyed for cardiovascular disease risk factors, body weight at age 25 from all participants were also obtained. Body mass index (BMI) at the age of 25 years was calculated with the weight at 25 years and the height measured during the survey, participants were divided into underweight (BMI<18.5 kg/m(2), n=1 331), normal-weight (18.5 kg/m(2)≤BMI <24 kg/m(2), n=10 400), overweight (24 kg/m(2)≤BMI<28 kg/m(2), n=2 019) and obesity (BMI≥28 kg/m(2), n=133) groups. Weight change was defined as the difference between the body weight at the age of 25 and at the survey and was grouped into<-7.5 kg (n=903), -7.5--2.6 kg (n=1 883), -2.5-2.5 kg (n=2 573), 2.6-7.5 kg (n=2 786), 7.6-12.5 kg (n=2 674) and>12.5 kg (n=3 064). The association of body weight status in early adulthood and body weight change from early adulthood to middle age with HDL-C level was examined by logistic regression model. The prevalence of low HDL-C in underweight, normal weight, overweight and obesity groups at age of 25 years were 10.7%(143/1 331), 15.5%(1 612/10 400), 16.3%(330/2 019) and 24.8%(33/133), respectively(P for trend <0.01). The prevalence of low HDL-C for adult weight change were 8.8%(79/903), 8.0%(151/1 883), 10.5%(269/2 573), 13.4%(373/2 786), 19.1%(511/2 674), and 24.0%(735/3 064)(P for trend <0.01)for weight change of <-7.5 kg, -7.5--2.6 kg, -2.5-2.5 kg, 2.6-7.5 kg, 7.6-12.5 kg and>12.5 kg, respectively. Multivariate logistic regression showed that overweight and obesity at age of 25 years and

Radiologic Changes by Early Motion in Neck Fractures of the Fifth Metacarpal Treated with Antegrade Intramedullary Fixation.

PubMed

Heo, Youn Moo; Kim, Sang Bum; Yi, Jin Woong; Kim, Tae Gyun; Lim, Byoung Gu

2016-02-01

As intramedullary (IM) fixation is one of the fixation methods used in neck fractures of the fifth metacarpal, an early motion of injured finger can be allowed. The purpose of this study is to evaluate whether immediate active motion affects the stability of antegrade IM fixation in surgical treatment of neck fractures of the fifth metacarpal bone and to assess related factors. Thirty one patients treated by closed reduction and antegrade IM fixation were consecutively enrolled. All patients started active motion of the little finger since 7 postoperative days and only daily activities including writing, typing or washing were allowed until the union of fracture. All fractures were healed within four to eight weeks. The changes of angulation, fifth metacarpal length and tip to head distance of K-wire were compared between immediate postoperative radiographs and radiographs at eight weeks. In addition, the effects by age, gender, initial angulation and comminution of the metacarpal neck were assessed. The average change of angulation was 0.12°, 5th metacarpal length was 1.49mm and tip to head distance of K-wire was 1.31mm. There was no significant difference in the change of angulation (p = 0.137). But, there were significant differences in the change of 5th metacarpal length and tip to head distance of K-wire ([Formula: see text]). The change of angulation was related to a comminution of the metacarpal neck and that of 5th metacarpal length was related to age and sex. The change of 5th metacarpal length and tip to head distance of K-wire can occur by an early mobilization in the antegrade IM fixation for neck fractures of the fifth metacarpal. However, we thought that an early active motion after surgery is important to increase the patients' satisfaction, even though careful selection of candidates is necessary.

Changes in beverage consumption from pre-pregnancy to early pregnancy in the Norwegian Fit for Delivery study.

PubMed

Skreden, Marianne; Bere, Elling; Sagedal, Linda R; Vistad, Ingvild; Øverby, Nina C

2015-05-01

To describe changes in consumption of different types of beverages from pre-pregnancy to early pregnancy, and to examine associations with maternal age, educational level and BMI. Cross-sectional design. Participants answered an FFQ at inclusion into a randomized controlled trial, the Fit for Delivery (FFD) trial, in median gestational week 15 (range: 9-20), reporting current consumption and in retrospect how often they drank the different beverages pre-pregnancy. Eight local antenatal clinics in southern Norway from September 2009 to February 2013. Five hundred and seventy-five healthy pregnant nulliparous women. Pre-pregnancy, 27 % reported drinking alcohol at least once weekly, compared with none in early pregnancy (P<0.001). The percentage of women drinking coffee (38 % v. 10 %, P<0.001), sugar-sweetened beverages (10 % v. 6 %, P=0.011) and artificially sweetened beverages (12 % v. 9 %, P=0.001) at least daily decreased significantly from pre-pregnancy to early pregnancy, while the percentage of women who reported to drink water (85 % v. 92 %, P<0.001), fruit juice (14 % v. 20 %, P=0.001) and milk (37 % v. 42 %, P=0.001) at least daily increased significantly. From pre-pregnancy to early pregnancy higher educated women reduced their consumption frequency of coffee significantly more than women with lower education. Older women reduced their consumption frequency of coffee and artificially sweetened beverages and increased their consumption frequency of fruit juice and milk significantly more than younger women. There is a significant change in beverage consumption from pre-pregnancy to early pregnancy among Norwegian nulliparous women.

[Integrated therapeutic strategy in large bowel neoplastic occlusion. An innovative therapeutic protocol].

PubMed

Gattai, Riccardo; Mascitelli, Erminia Macera; Bechi, Paolo; Pace, Marcello

2007-01-01

Occlusive complication is a common event in the colo-rectal cancer (20-30% of cases). Operative mortality and 5 yrs survival of not occlusive cancer vs occlusive cancer is 11% vs 23% and 45% vs 25% rispectively. In occlusive cancer the level of parietal infiltration affects considerably the local and peritoneal recurrence. 50% of all patients underwent a surgical re-operation for colo-rectal cancer have peritoneal neoplastic implant. The resolution of occlusive complication in immediate or delayed urgency with decompressive derivation, it allows to perform an integrated treatment of choice that it could guarantee the oncological radical procedure. RATIONALE-METHODS: The intraperitoneal hyperthermic chemotherapy (IPHC) combined with radical or cytoriductive surgery performs its action through sinergistic effects of high dosage and concentration of drugs and hyperthermia. These agents perform a cell killing with a direct contact against micro and/or macroscopic neoplastic residue. In radical surgery with curative intent, the association with IPHC ("preventive" adjuvant) has got as objective the distruction of microscopic local or peritoneal metastasis. In occlusive cancer with synchronous or metachronous peritoneal carcinomatosis, the performance of the cytoreductive surgery with IPHC ("therapeutic" adjuvant) is the only treatment that improves the survival and the quality of remainig life. The clinical results reported by many Istitutions indicates that the 2-5 yrs survivals are 45-60% and 20-30% rispectively. These data lead us to believe that an optimal eradication of micro and/or macroscopic peritoneal spreading could be optained also in occlusive colo-rectal cancer.

Differentiation between inflammatory and neoplastic orbital conditions based on computed tomographic signs.

PubMed

Lederer, Kristina; Ludewig, Eberhard; Hechinger, Harald; Parry, Andrew T; Lamb, Christopher R; Kneissl, Sibylle

2015-07-01

To identify computed tomographic (CT) signs that could be used to differentiate inflammatory from neoplastic orbital conditions in small animals. Fifty-two animals (25 cats, 21 dogs, 4 rabbits, and 2 rodents). Case-control study in which CT images of animals with histopathologic diagnosis of inflammatory (n = 11), neoplastic orbital conditions (n = 31), or normal control animals (n = 10) were reviewed independently by five observers without the knowledge of the history or diagnosis. Observers recorded their observations regarding specific anatomical structures within the orbit using an itemized form containing the following characteristics: definitely normal; probably normal; equivocal; probably abnormal; and definitely abnormal. Results were statistically analyzed using Fleiss' kappa and logistic regression analyses. The overall level of agreement between observers about the presence or absence of abnormal CT signs in animals with orbital disease was poor to moderate, but was highest for observations concerning orbital bones (κ = 0.62) and involvement of the posterior segment (κ = 0.52). Significant associations between abnormalities and diagnosis were found for four structures: Abnormalities affecting orbital bones (odds ratio [OR], 1.7) and anterior ocular structures (OR, 1.5) were predictive of neoplasia, while abnormalities affecting extraconal fat (OR, 1.7) and skin (OR, 1.4) were predictive of inflammatory conditions. Orbital CT is an imaging test with high specificity. Fat stranding, a CT sign not previously emphasized in veterinary medicine, was significantly associated with inflammatory conditions. Low observer agreement probably reflects the limited resolution of CT for small orbital structures. © 2014 American College of Veterinary Ophthalmologists.

Early changes of blood lipid levels during psychotropic drug treatment as predictors of long-term lipid changes and of new onset dyslipidemia.

PubMed

Delacrétaz, Aurélie; Vandenberghe, Frederik; Gholam-Rezaee, Mehdi; Saigi Morgui, Nuria; Glatard, Anaïs; Thonney, Jacques; Solida-Tozzi, Alessandra; Kolly, Stéphane; Gallo, Sylfa Fassassi; Baumann, Philipp; Berney, Sylvie; Zulauff, Sandrine Valloton; Aubry, Jean-Michel; Hasler, Roland; Ebbing, Karsten; von Gunten, Armin; Conus, Philippe; Eap, Chin B

Cardiovascular diseases and dyslipidemia represent a major health issue in psychiatry. Many psychotropic drugs can induce a rapid and substantial increase of blood lipid levels. This study aimed to determine the potential predictive power of an early change of blood lipid levels during psychotropic treatment on long-term change and on dyslipidemia development. Data were obtained from a prospective study including 181 psychiatric patients with metabolic parameters monitored during the first year of treatment and with adherence ascertained. Blood lipid levels (ie, total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], non-high-density lipoprotein cholesterol [non-HDL-C], and fasting triglycerides [TGs]) were measured at baseline and after 1, 3, and/or 12 months of treatment. Receiver-operating characteristic analyses indicated that early (ie, after 1 month of psychotropic treatment) increases (≥5%) for TC, LDL-C, TG, and non-HDL-C and decrease (≥5%) for HDL-C were the best predictors for clinically relevant modifications of blood lipid levels after 3 months of treatment (≥30% TC, ≥40% LDL-C, ≥45% TG, ≥55% non-HDL-C increase, and ≥20% HDL-C decrease; sensitivity 70%-100%, specificity 53%-72%). Predictive powers of these models were confirmed by fitting longitudinal multivariate models in the same cohort (P ≤ .03) as well as in a replication cohort (n = 79; P ≤ .003). Survival models showed significantly higher incidences of new onset dyslipidemia (TC, LDL-C, and non-HDL-C hypercholesterolemia, HDL-C hypocholesterolemia, and hypertriglyceridemia) for patients with early changes of blood lipid levels compared to others (P ≤ .01). Early modifications of blood lipid levels following prescription of psychotropic drugs inducing dyslipidemia should therefore raise questions on clinical strategies to control long-term dyslipidemia. Copyright © 2017 National Lipid Association. Published

LASER BIOLOGY AND MEDICINE: Combined application of optical methods to increase the information content of optical coherent tomography in diagnostics of neoplastic processes

NASA Astrophysics Data System (ADS)

Kuranov, R. V.; Sapozhnikova, V. V.; Shakhova, N. M.; Gelikonov, V. M.; Zagainova, E. V.; Petrova, S. A.

2002-11-01

A combined application of optical methods [optical coherent tomography (OCT), cross-polarisation optical coherent tomography, and fluorescence spectroscopy] is proposed for obtaining information on morphological and biochemical changes occurring in tissues in norm and pathology. It is shown that neoplastic and scar changes in esophagus can be distinguished using a combination of polarisation and standard OCT due to the difference between the depolarising properties of the tissues caused by the structural properties of collagenic fibres in stroma. It is shown that OCT combined with fluorescence spectroscopy with the use of 5-aminolevulinic acid is promising for determining the boundaries of carcinoma of the uterine cervix and vulva. It is found that the tumour boundary detected by optical methods coincides with the morphological boundary and extends beyond colposcopically determined boundary by about 2 mm.

Strengths and Weaknesses of Sea Ice as a Potential Early Indicator of Climate Change,

DTIC Science & Technology

Sea ice is examined for its potential as an early indicator of climate change by considering how well it satisfies four criteria listed as desired... climate change , sea ice is unlikely any time in the near future to be a definitive early indicator of climate change when considered by itself.

Changing Bilingual Self-Perceptions from Early Adolescence to Early Adulthood: Empirical Evidence from a Mixed-Methods Case Study

ERIC Educational Resources Information Center

Caldas, Stephen J.

2008-01-01

In the emerging tradition of language socialization research, this study examines the changing bilingual self-perceptions of three children, identical twin girls and their older brother, from early adolescence through early adulthood. The children were reared in a predominantly French-speaking home in south Louisiana by French/English bilingual…

Early changes in plasma glucagon and growth hormone response to oral glucose in experimental hyperthyroidism.

PubMed

Tosi, F; Moghetti, P; Castello, R; Negri, C; Bonora, E; Muggeo, M

1996-08-01

The mechanisms underlying deterioration of glucose tolerance associated with hyperthyroidism are not completely understood. Increases in glucagon and growth hormone (GH) secretion have been previously found in hyperthyroid subjects, and could play a crucial role in this phenomenon. However, studies have not yet established the time sequence of changes in plasma glucose on the one hand and glucagon and GH on the other. To assess the early effects of thyroid hormone excess on glucose tolerance and plasma concentrations of the main glucoregulatory hormones, 12 nondiabetic euthyroid subjects underwent an oral glucose tolerance test (OGTT) before and after triiodothyronine ([T3] 120 micrograms/d) was administered for 10 days. Plasma levels of glucose, insulin, glucagon, and GH were determined at fasting and after the glucose load. T3 administration caused a marked increase in serum T3 (8.8 +/- 0.6 v 2.0 +/- 0.1 nmol/L), with clinical and biochemical signs of thyrotoxicosis. During the treatment, plasma glucose significantly increased both at fasting and after the glucose load (basal, 5.3 +/- 0.1 v 4.9 +/- 0.2 mmol/L, P < .05; area under the curve [AUC] for OGTT, 7.7 +/- 0.3 v 6.7 +/- 0.4 mmol/L min, P < .01) without any change in plasma insulin levels. After T3 administration, plasma glucagon levels were lower than at baseline (basal, 92 +/- 7 v 148 +/- 35 ng/L; AUC, 74 +/- 6 v 98 +/- 16 ng/L.min, P < .05), showing an appropriate reduction by the increased glucose levels. Conversely, plasma GH showed impaired suppression by hyperglycemia (AUC, 1.2 +/- 0.3 v 0.7 +/- 0.2 microgram/L.min, P < .05). In conclusion, thyroid hormone excess rapidly impairs glucose tolerance. Altered secretion of GH is an early event in thyrotoxicosis accompanying the onset of hyperglycemia, whereas plasma glucagon is appropriately suppressed by the increased plasma glucose levels. Thus, GH but not glucagon may contribute to the early hyperglycemic effect of thyrotoxicosis.

Is there an association with constitutional structural chromosomal abnormalities and hematologic neoplastic process? A short review.

PubMed

Panani, Anna D

2009-04-01

The occasional observation of constitutional chromosomal abnormalities in patients with a malignant disease has led to a number of studies on their potential role in cancer development. Investigations of families with hereditary cancers and constitutional chromosomal abnormalities have been key observations leading to the molecular identification of specific genes implicated in tumorigenesis. Large studies have been reported on the incidence of constitutional chromosomal aberrations in patients with hematologic malignancies, but they could not confirm an increased risk for hematologic malignancy among carriers of structural chromosomal changes. However, it is of particular interest that constitutional structural aberrations with breakpoints similar to leukemia-associated specific breakpoints have been reported in patients with hematologic malignancies. Because of insufficient data, it remains still unclear if these aberrations represent random events or are associated with malignancy. There has been a substantial discussion about mechanisms involved in constitutional structural chromosomal changes in the literature. The documentation of more patients with constitutional structural chromosomal changes could be of major importance. Most importantly, the molecular investigation of chromosomal regions involved in rearrangements could give useful information on the genetic events underlying constitutional anomalies, contributing to isolation of genes important in the development of the neoplastic process. Regarding constitutional anomalies in patients with hematologic disorders, a survey of the cytogenetic data of our cytogenetics unit is herein also presented.

Eosinophils as a marker for invasion in vulvar squamous neoplastic lesions.

PubMed

Spiegel, Gregory W

2002-04-01

A study of eosinophils directed against vulvar neoplastic squamous epithelium was undertaken to determine whether there were thresholds per high-power field (hpf) or 10 hpf that were a marker for invasion. The presence of stromal and intraepithelial eosinophils in 33 cases of vulvar grade 3 squamous intraepithelial neoplasia (carcinoma in situ) (VIN 3) was compared with that in 38 cases of vulvar invasive carcinoma with any degree of invasion (ISC). In both incisional biopsy and excisional specimens, the presence of >3 eosinophils per high-power field (eos/hpf) and the presence of >or=5 eosinophils per 10 high-power fields (eos/10 hpf) were both significantly associated with invasion, and the presence of >or=20 eos/hpf and/or >50 eos/10 hpf was limited to cases with invasion. The presence of eosinophils within the neoplastic squamous epithelium was also limited to cases with invasion. The author proposes: 1) eosinophil counts in vulvar incisional biopsy specimens of >3/hpf and/or >or=5/10 hpf warrant a note of caution that invasion may be present even when none is identified by conventional criteria; 2) eosinophil counts of >3/hpf and/or >or=5/10 hpf in excisional specimens should raise the suspicion of invasion in cases in which only VIN 3 is identified in the initial sections, and warrant additional sections and/or levels to search for invasion; 3) the above eosinophil counts provide supportive evidence for invasion in cases with equivocal invasion by conventional criteria; and 4) the presence of >or=20 eos/hpf and/or >50 eos/10 hpf, and the presence of intraepithelial eosinophils in conjunction with >3 eos/hpf and >or=5 eos/10 hpf is virtually diagnostic of invasion.

Hypothesis: Induction of biomarkers for detection of colonic neoplasms

PubMed Central

Bordonaro, Michael; Lazarova, Darina

2018-01-01

The signing of the National Cancer Act of 1971 by President Nixon marked the beginning of our war on cancer. More than 45 years later, the war is still going steady, with the enemy being almost as strong as in 1971. Furthermore, the increasing rates of obesity not only among adults, but among children and adolescents, are the likely cause for the 30-year trend of colon cancer (CC) becoming a disease of the younger population in the U.S. These trends, however, have not spurred the development of novel screening approaches for CC. Considering the need for a sensitive and non-invasive detection of early stage neoplastic lesions in the colon, we propose the development of a test based on a novel concept - the concept of induced biomarkers. The proposal is based upon our findings that the food additives propolis and gamma-cyclodextrin (gCD) (a) decrease the neoplastic burden in normal weight and obese ApcMin mice, a model of early stage intestinal neoplasia, and (b) elicit significant changes in the serum proteome in ApcMin mice. We posit that gCD and propolis induce the release of neoplasm-associated biomarkers in systemic circulation (e.g., metabolites, neoplastic, apoptotic, and immune response proteins), and these markers could be used to detect early stage intestinal neoplasms. Additional dietary bioactives may also elicit a complement of induced markers. The hypothesis could be ascertained by utilizing a mouse model, the Apc+/1638Nmice, as well as through human subject studies that integrate proteomics and metabolomics analyses. The concept of detecting inducible markers of colonic neoplasms is novel, and is substantiated by the significant physiological effects of gCD and propolis on neoplastic colonic cells in culture and on early neoplastic development in ApcMinmice. The long-term objective is to develop a minimally invasive method that detects early stage neoplastic development in the human colon. PMID:29290782

Mexican-Origin Youth's Cultural Orientations and Adjustment: Changes from Early to Late Adolescence

PubMed Central

Updegraff, Kimberly A.; Umaña-Taylor, Adriana J.; McHale, Susan M.; Wheeler, Lorey A.; Perez-Brena, Norma

2013-01-01

Drawing from developmental and cultural adaptation perspectives and using a longitudinal design, this study examined: (a) mean-level changes in Mexican-origin adolescents’ cultural orientations and adjustment from early to late adolescence; and (b) bidirectional associations between cultural orientations and adjustment using a cross-lag panel model. Participants included 246 Mexican-origin, predominantly immigrant families that participated in home interviews and a series of nightly phone calls when target adolescents were 12 years and 18 years of age. Girls exhibited more pronounced declines in traditional gender role attitudes than did boys, and all youth declined in familism values, time spent with family, and involvement in Mexican culture. Bidirectional relations between cultural orientations and adjustment emerged, and some associations were moderated by adolescent nativity and gender. PMID:22966929

Infant pain-related negative affect at 12 months of age: early infant and caregiver predictors.

PubMed

Din Osmun, Laila; Pillai Riddell, Rebecca; Flora, David B

2014-01-01

To examine the predictive relationships of early infant and caregiver variables on expressed pain-related negative affect duration at the 12-month immunization. Infants and their caregivers (N = 255) were followed during immunization appointments over the first year of life. Latent growth curve modeling in a structural equation modeling context was used. Higher levels of initial infant pain reactivity at 2 months and caregiver emotional availability averaged across 2, 4, and 6 months of age were related to larger decreases in the duration of infant negative affect over the first 6 months of life. Longer duration of infant negative affect at 2 months and poorer regulation of infant negative affect over the first 6 months of life predicted longer durations of infant negative affect by 12 months. Infant negative affect at 12 months was a function of both infant factors and the quality of caregiver interactive behaviors (emotional availability) in early infancy.

Changing skewness: an early warning signal of regime shifts in ecosystems.

PubMed

Guttal, Vishwesha; Jayaprakash, Ciriyam

2008-05-01

Empirical evidence for large-scale abrupt changes in ecosystems such as lakes and vegetation of semi-arid regions is growing. Such changes, called regime shifts, can lead to degradation of ecological services. We study simple ecological models that show a catastrophic transition as a control parameter is varied and propose a novel early warning signal that exploits two ubiquitous features of ecological systems: nonlinearity and large external fluctuations. Either reduced resilience or increased external fluctuations can tip ecosystems to an alternative stable state. It is shown that changes in asymmetry in the distribution of time series data, quantified by changing skewness, is a model-independent and reliable early warning signal for both routes to regime shifts. Furthermore, using model simulations that mimic field measurements and a simple analysis of real data from abrupt climate change in the Sahara, we study the feasibility of skewness calculations using data available from routine monitoring.

Cognitive Changes After Adjuvant Treatment in Older Adults with Early-Stage Breast Cancer.

PubMed

Lange, Marie; Heutte, Natacha; Noal, Sabine; Rigal, Olivier; Kurtz, Jean-Emmanuel; Lévy, Christelle; Allouache, Djelila; Rieux, Chantal; Lefel, Johan; Clarisse, Bénédicte; Leconte, Alexandra; Veyret, Corinne; Barthélémy, Philippe; Longato, Nadine; Tron, Laure; Castel, Hélène; Eustache, Francis; Giffard, Bénédicte; Joly, Florence

2018-06-22

Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls. Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status. The sample consisted of women newly diagnosed with EBC ( n  = 118) and healthy controls ( n  = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant ( p  = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline. This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC. The Oncologist IMPLICATIONS FOR PRACTICE: After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced

The relationship between early changes in the HAMD-17 anxiety/somatization factor items and treatment outcome among depressed outpatients.

PubMed

Farabaugh, Amy; Mischoulon, David; Fava, Maurizio; Wu, Shirley L; Mascarini, Alessandra; Tossani, Eliana; Alpert, Jonathan E

2005-03-01

The 17-item Hamilton Rating Scale for Depression (HAMD-17) Anxiety/Somatization factor includes six items: Anxiety (psychic), Anxiety (somatic), Somatic Symptoms (gastrointestinal), Somatic Symptoms (general), Hypochondriasis and Insight. This study examines the relationship between early changes (defined as those observed between baseline and week 1) in these HAMD-17 Anxiety/Somatization Factor items and treatment outcome among major depressive disorder (MDD) patients who participated in a study comparing the antidepressant efficacy of a standardized extract of hypericum with both placebo and fluoxetine. Following a 1-week, single-blind washout, patients with MDD diagnosed by the Structured Clinical Interview for DSM-IV (SCID) were randomized to 12 weeks of double-blind treatment with hypericum extract (900 mg/day), fluoxetine (20 mg/day) or placebo. The relationship between early changes in HAMD-17 anxiety/somatization factor items and treatment outcome was assessed separately for patients who received study treatment (hypericum or fluoxetine) versus placebo with a logistic regression method. One hundred and thirty-five patients (female 57%, mean age=37.3+/-11.0 years; mean baseline HAMD-17=19.7+/-3.2 years) were randomized to double-blind treatment and were included in the intent-to-treat (ITT) analyses. After adjusting for baseline HAMD-17 scores and for multiple comparisons with the Bonferroni correction, patients who remitted (HAMD-17 score <8) after study treatment had significantly greater early improvement in Somatic Symptoms (General) scores than non-remitters. No other significant differences in early changes were noted for the remaining items between remitters versus non-remitters who received active treatment. For patients treated with placebo, early change was not predictive of remission for any of the items after Bonferroni correction. In conclusion, the presence of early improvement on the HAMD-17 item concerning fatigue and general somatic symptoms

Late-Glacial to Early Holocene Climate Changes from a Central Appalachians Pollen and Macrofossil Record

NASA Technical Reports Server (NTRS)

Kneller, Margaret; Peteet, Dorothy

1997-01-01

A Late-glacial to early Holocene record of pollen, plant macrofossils and charcoal, based on two cores, is presented for Browns Pond in the central Appalachians of Virginia. An AMS radiocarbon chronology defines the timing of moist and cold excursions, superimposed upon the overall warming trend from 14,200 to 7,500 C-14 yr B.P. This site shows cold, moist conditions from approximately 14,200 to 12,700 C-14 yr B.P., with warming at 12,730, 11,280 and 10,050 C-14 yr B.P. A decrease in deciduous broad-leaved tree taxa and Pinus strobus (haploxylon) pollen, simultaneous with a re-expansion of Abies denotes a brief, cold reversal from 12,260 to 12,200 C-14 yr B.P. A second cold reversal, inferred from increases in montane conifers, is centered at 7,500 C-14 yr B.P. The cold reversals at Browns Pond may be synchronous with climate change in Greenland, and northwestern Europe. Warming at 11,280 C-14 yr B.P. shows the complexity of regional climate responses during the Younger Dryas chronozone.

Potential late health effects of depleted uranium and tungsten used in armor-piercing munitions: comparison of neoplastic transformation and genotoxicity with the known carcinogen nickel.

PubMed

Miller, Alexandra C; Xu, Jiaquan; Stewart, Michael; Prasanna, Pataje G S; Page, Natalie

2002-02-01

Limited data exist to permit an accurate assessment of risks for carcinogenesis and mutagenesis from embedded fragments or inhaled particulates of depleted uranium (DU). Ongoing studies have been designed to provide information about the carcinogenic potential of DU using in vitro and in vivo assessments of morphological transformation as well as cytogenetic, mutagenic, and oncogenic effects. For comparison, we also examined tungsten alloys used in military projectiles and the known carcinogen nickel. Quantitative and qualitative in vitro transformation studies were done to assess the carcinogenic potential of radiation and chemical hazards. Using a human osteosarcoma cell model, we demonstrated that soluble and insoluble DU compounds can transform cells to the tumorigenic phenotype, as characterized by morphological, biochemical, and oncogenic changes consistent with tumor cell behavior. Tungsten alloys and nickel were also shown to be neoplastic transforming agents, although at a frequency less than that of DU. Sister chromatid exchange, micronuclei, and alkaline filter elution assays showed DU and tungsten alloys were genotoxic. Exposure to a nontoxic, nontransforming dose of DU induced a small but statistically significant increase in the number of dicentrics formed in cells. These results suggest that long-term exposure to DU or tungsten alloys could be critical to the development of neoplastic disease in humans and that additional studies are needed.

From early stress to 12-month development in very preterm infants: Preliminary findings on epigenetic mechanisms and brain growth.

PubMed

Fumagalli, Monica; Provenzi, Livio; De Carli, Pietro; Dessimone, Francesca; Sirgiovanni, Ida; Giorda, Roberto; Cinnante, Claudia; Squarcina, Letizia; Pozzoli, Uberto; Triulzi, Fabio; Brambilla, Paolo; Borgatti, Renato; Mosca, Fabio; Montirosso, Rosario

2018-01-01

Very preterm (VPT) infants admitted to Neonatal Intensive Care Unit (NICU) are at risk for altered brain growth and less-than-optimal socio-emotional development. Recent research suggests that early NICU-related stress contributes to socio-emotional impairments in VPT infants at 3 months through epigenetic regulation (i.e., DNA methylation) of the serotonin transporter gene (SLC6A4). In the present longitudinal study we assessed: (a) the effects of NICU-related stress and SLC6A4 methylation variations from birth to discharge on brain development at term equivalent age (TEA); (b) the association between brain volume at TEA and socio-emotional development (i.e., Personal-Social scale of Griffith Mental Development Scales, GMDS) at 12 months corrected age (CA). Twenty-four infants had complete data at 12-month-age. SLC6A4 methylation was measured at a specific CpG previously associated with NICU-related stress and socio-emotional stress. Findings confirmed that higher NICU-related stress associated with greater increase of SLC6A4 methylation at NICU discharge. Moreover, higher SLC6A4 discharge methylation was associated with reduced anterior temporal lobe (ATL) volume at TEA, which in turn was significantly associated with less-than-optimal GMDS Personal-Social scale score at 12 months CA. The reduced ATL volume at TEA mediated the pathway linking stress-related increase in SLC6A4 methylation at NICU discharge and socio-emotional development at 12 months CA. These findings suggest that early adversity-related epigenetic changes might contribute to the long-lasting programming of socio-emotional development in VPT infants through epigenetic regulation and structural modifications of the developing brain.

Early-Middle Pleistocene environmental changes and human evolution in the Italian peninsula

NASA Astrophysics Data System (ADS)

Manzi, Giorgio; Magri, Donatella; Palombo, Maria Rita

2011-06-01

This paper is aimed to elucidate the ecological scenario in Italy in the Early to Middle Pleistocene, when species of the genus Homo are known to spread across Europe in two distinct waves: earlier than 1.2 Ma and at about 600 ka, respectively. This topic represents both (1) a fundamental aspect for a better understanding of the factors that allowed humans to colonize the middle latitudes of Eurasia, and (2) a reasonable frontier for current Quaternary palaeobiology, thanks to increasing knowledge of regional and local patterns. As for Italy, a combination of palaeobotanical and palaeontological data sets shows on the one hand a general complexity in both space and time, and on the other hand changes of considerable importance within and among the biological communities. These changes had a major importance during the worldwide change in the Earth climatic system known as "Middle Pleistocene Revolution", which according to our data culminates with crucial effects of the extreme conditions of MIS 16. Subsequently, during great part of the Middle Pleistocene, the peculiar features of the Italian territory may have favoured isolation and a local persistence of plant populations and possibly mammal taxa, humans included, as for instance suggested by the corrected chronology of the Ceprano calvarium.

Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults.

PubMed

Pfeifer, M; Verhovec, R; Zizek, B; Prezelj, J; Poredos, P; Clayton, R N

1999-02-01

Hypopituitary patients have increased mortality from vascular disease, and in these patients, early markers of atherosclerosis [increased carotid artery intima-media thickness (IMT) and reduced distensibility] are more prevalent. As GH replacement can reverse some risk factors of atherosclerosis, the present study examined the effect of GH treatment on morphological and functional changes in the carotid and brachial arteries of GH-deficient (GHD) adults. Eleven GHD hypopituitary men (24-49 yr old) were treated with recombinant human GH (0.018 U/kg BW x day) for 18 months. IMT of the common carotid artery (CCA) and the carotid bifurcation (CB), and flow-mediated endothelium-dependent dilation (EDD) of the brachial artery were measured by B mode ultrasound before and at 3, 6, 12, and 18 months of treatment, and values were compared with those in 12 age-matched control men. Serum concentrations of lipids, lipoprotein(a), insulin-like growth factor I (IGF-I), and IGF-binding protein-3 (IGFBP-3) were also measured. In GHD men before treatment the IMTs of the CCA [mean(SD), 0.67(0.05) mm] and CB [0.75(0.04) mm] were significantly greater (P < 0.001) than those in control men [0.52(0.07) and 0.65(0.07) mm, respectively]. GH treatment normalized the IMT of the CCA by 6 months [0.53(0.04) mm] and that of the CB by 3 months [0.68(0.05) mm]. The IMT of the carotid artery (CCA and CB) was negatively correlated with serum IGF-I (r = -0.53; P < 0.0001). There was a significant improvement in flow-mediated EDD of the brachial artery at 3 months, which was sustained at 6 and 18 months of GH treatment (P < 0.05). GH treatment increased high density lipoprotein cholesterol at 3 and 6 months, but did not reduce total or low density lipoprotein cholesterol and was without effect on lipoprotein(a). There was no correlation between plasma lipids and changes in IMT or EDD of the arteries examined. In conclusion, GH treatment of hypopituitary GHD men reverses early morphological and

Early versus delayed invasive strategy for intermediate- and high-risk acute coronary syndromes managed without P2Y12 receptor inhibitor pretreatment: Design and rationale of the EARLY randomized trial.

PubMed

Lemesle, Gilles; Laine, Marc; Pankert, Mathieu; Puymirat, Etienne; Cuisset, Thomas; Boueri, Ziad; Maillard, Luc; Armero, Sébastien; Cayla, Guillaume; Bali, Laurent; Motreff, Pascal; Peyre, Jean-Pascal; Paganelli, Franck; Kerbaul, François; Roch, Antoine; Michelet, Pierre; Baumstarck, Karine; Bonello, Laurent

2018-01-01

According to recent literature, pretreatment with a P2Y 12 ADP receptor antagonist before coronary angiography appears no longer suitable in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) due to an unfavorable risk-benefit ratio. Optimal delay of the invasive strategy in this specific context is unknown. We hypothesize that without P2Y 12 ADP receptor antagonist pretreatment, a very early invasive strategy may be beneficial. The EARLY trial (Early or Delayed Revascularization for Intermediate- and High-Risk Non-ST-Segment Elevation Acute Coronary Syndromes?) is a prospective, multicenter, randomized, controlled, open-label, 2-parallel-group study that plans to enroll 740 patients. Patients are eligible if the diagnosis of intermediate- or high-risk NSTE-ACS is made and an invasive strategy intended. Patients are randomized in a 1:1 ratio. In the control group, a delayed strategy is adopted, with the coronary angiography taking place between 12 and 72 hours after randomization. In the experimental group, a very early invasive strategy is performed within 2 hours. A loading dose of a P2Y 12 ADP receptor antagonist is given at the time of intervention in both groups. Recruitment began in September 2016 (n = 558 patients as of October 2017). The primary endpoint is the composite of cardiovascular death and recurrent ischemic events at 1 month. The EARLY trial aims to demonstrate the superiority of a very early invasive strategy compared with a delayed strategy in intermediate- and high-risk NSTE-ACS patients managed without P2Y 12 ADP receptor antagonist pretreatment. © 2018 Wiley Periodicals, Inc.

Deficient Repair of Particulate Hexavalent chromium-Induced DNA Double Strand Breaks Leads To Neoplastic Transformation

PubMed Central

Xie, Hong; Wise, Sandra S.; Wise, John. P.

2008-01-01

Hexavalent chromium (Cr(VI)) is a potent respiratory toxicant and carcinogen. The most carcinogenic forms of Cr(VI) are the particulate salts such as lead chromate, which deposit and persist in the respiratory tract after inhalation. We demonstrate here that particulate chromate induces DNA double strand breaks in human lung cells with 0.1, 0.5, and 1 ug/cm2 lead chromate inducing 1.5, 2 and 5 relative increases in the percent of DNA in the comet tail, respectively. These lesions are repaired within 24 h and require Mre11 expression for their repair. Particulate chromate also caused Mre11 to co-localize with gamma-H2A.X and ATM. Failure to repair these breaks with Mre11 induced neoplastic transformation including loss of cell contact inhibition and anchorage independent growth. A 5-day exposure to lead chromate induced loss of cell contact inhibition in a concentration-dependent manner with 0, 0.1, 0.5 and 1 ug/cm2 lead chromate inducing 1, 78 and 103 foci in 20 dishes, respectively. These data indicate that Mre11 is critical to repairing particulate Cr(VI)-induced double strand breaks and preventing Cr(VI)-induced neoplastic transformation. PMID:18023605

Extra-prostatic Transgene-associated Neoplastic Lesions in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice

PubMed Central

Berman-Booty, Lisa D.; Thomas-Ahner, Jennifer M.; Bolon, Brad; Oglesbee, Michael J.; Clinton, Steven K.; Kulp, Samuel K.; Chen, Ching-Shih; La Perle, Krista

2014-01-01

Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of pre-neoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubulo-acinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here we describe the histologic and immunohistochemical features of two novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain, and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice as well as in male TRAMP mice without histologically apparent prostate tumors. In this paper we also calculate the incidences of the urethral carcinomas and renal tubulo-acinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice. PMID:24742627

Differential expression of extracellular matrix molecules and the alpha 6-integrins in the normal and neoplastic prostate.

PubMed Central

Knox, J. D.; Cress, A. E.; Clark, V.; Manriquez, L.; Affinito, K. S.; Dalkin, B. L.; Nagle, R. B.

1994-01-01

The epithelial basal lamina composition and integrin expression profile of normal and neoplastic human prostate was characterized using immunohistochemical analysis of frozen samples. The major components of the basal lamina surrounding normal acini were laminin, type IV collagen, entactin, and type VII collagen with variable amounts of tenascin. The basal lamina of neoplastic acini had a similar composition, except for the loss of type VII collagen, which was observed in all grades of carcinoma. The basal cells of the normal prostate express the alpha 6-, beta 1-, and beta 4-integrin subunits, suggesting that both the alpha 6 beta 1- and alpha 6 beta 4-integrin complexes are formed. In prostate carcinoma there is a complete loss of beta 4 expression and the alpha 6- and beta 1-integrin subunits, which are restricted to the basal and basal lateral surfaces of basal cells, are distributed diffusely throughout the cytoplasmic membrane. The differential expression of type VII collagen and beta 4 are discussed in relationship to their possible role in tumor progression. Images Figure 1 Figure 2 Figure 3 PMID:8030747

Relationships Between Weight Change and Physical and Psychological Distress in Early-Stage Breast Cancer Survivors.

PubMed

Vance, Vivienne; Mourtzakis, Marina; Hanning, Rhona

2018-05-26

Weight gain and unfavorable changes in body composition are common in a growing population of breast cancer survivors, but the etiology of these changes is poorly understood. The aim of this study was to investigate relationships between weight change and symptoms of physical and psychological distress in the first 12 months of completing treatment in women who had completed treatment for breast cancer. Physical distress and psychological distress were assessed using the Rotterdam Symptom Checklist, the Distress Thermometer, and the Fatigue Symptom Inventory. Weight change in 28 women since the completion of treatment (mean, 6.4 ± 4.4 months) ranged from -6.0 kg to +5.2 kg (mean, -0.4 ± 3.2), with 6 women gaining and 7 women losing an average of 3.5 ± 1.0 and 5.1 ± 0.8 kg, respectively. Rotterdam mean scores for physical (17.5 ± 9.0) and psychological distress (27.1 ± 16.9) were similar to previous findings for patients with early-stage breast cancer in active treatment and appear to be markedly higher than distress levels previously reported in cancer-free adults. Distress levels, based on the Distress Thermometer, were moderate to severe in 35% of women. Fatigue was common and associated with interference in daily living for some women. Fatigue duration was negatively correlated with weight change (P = -0.46, P < .05). Symptoms of physical and psychological distress persist for some women in the first year after completing treatment and may associate with weight change. These findings underscore a need for ongoing assessment and supportive care across the breast cancer trajectory and may guide dietary counseling aimed at promoting healthy body weight and overall health in early survivorship.

12 CFR 250.180 - Reports of changes in control of management.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Reports of changes in control of management... FEDERAL RESERVE SYSTEM MISCELLANEOUS INTERPRETATIONS Interpretations § 250.180 Reports of changes in control of management. (a) Under a statute enacted September 12, 1964 (Pub. L. 88-593; 78 Stat. 940) all...

12 CFR 250.180 - Reports of changes in control of management.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Reports of changes in control of management... FEDERAL RESERVE SYSTEM MISCELLANEOUS INTERPRETATIONS Interpretations § 250.180 Reports of changes in control of management. (a) Under a statute enacted September 12, 1964 (Pub. L. 88-593; 78 Stat. 940) all...

Evaluation of the anti-neoplastic effect of sorafenib on liver cancer through bioluminescence tomography

NASA Astrophysics Data System (ADS)

Liang, Qian; Ye, Jinzuo; Du, Yang; Chi, Chongwei; Tian, Jie

2017-03-01

Hepatocellular carcinoma (HCC) is one of the most important leading causes of cancer-related deaths worldwide. In this study, we evaluated the efficacy of sorafenib on hepatocellular carcinoma through bioluminescence tomography (BLT) based on Micro-CT/BLT multi-modal system. Initially, the human hepatocellular carcinoma cell line HepG2-Red-FLuc, which was transfected with luciferase gene, was cultured. And then, the orthotopic liver tumor mouse model was established on 4 5 weeks old athymic male Balb/c nude mice by inoculating the HepG2-Red-FLuc cell suspension into the liver lobe under isoflurane anesthesia. 15 20 days after tumor cells implantation, the mice were divided into two groups including the sorafenib treatment group and the control group. The mice in the treatment group were treated with sorafenib with dosage of 62 mg/kg/day by oral gavage for continuous 14 days, and the mice in the control group were treated with sterile water at equal volume. The tumor growth and drug treatment efficacy were dynamically monitored through BLT. The results in this study showed that the growth of liver cancer can be dynamically monitored from very early stage, and also the sorafenib treatment efficacy can be reliably and objectively assessed using BLT imaging method. Our experimental result demonstrated sorafenib can inhibit the tumor growth effectively. BLT enabled the non-invasive and reliable assessment of anti-neoplastic drug efficacy on liver cancer.

ASXL1/EZH2 mutations promote clonal expansion of neoplastic HSC and impair erythropoiesis in PMF.

PubMed

Triviai, Ioanna; Zeschke, Silke; Rentel, Jan; Spanakis, Marios; Scherer, Theo; Gabdoulline, Razif; Panagiota, Victoria; Thol, Felicitas; Heuser, Michael; Stocking, Carol; Kröger, Nicolaus

2018-06-15

Primary myelofibrosis (PMF) is a hematopoietic stem cell (HSC) disease, characterized by aberrant differentiation of all myeloid lineages and profound disruption of the bone marrow niche. PMF samples carry several mutations, but their cell origin and hierarchy in regulating the different waves of clonal and aberrant myeloproliferation from the prime HSC compartment is poorly understood. Genotyping of >2000 colonies from CD133+HSC and progenitors from PMF patients confirmed the complex genetic heterogeneity within the neoplastic population. Notably, mutations in chromatin regulators ASXL1 and/or EZH2 were identified as the first genetic lesions, preceding both JAK2-V617F and CALR mutations, and are thus drivers of clonal myelopoiesis in a PMF subset. HSC from PMF patients with double ASXL1/EZH2 mutations exhibited significantly higher engraftment in immunodeficient mice than those from patients without histone modifier mutations. EZH2 mutations correlate with aberrant erythropoiesis in PMF patients, exemplified by impaired maturation and cell cycle arrest of erythroid progenitors. These data underscore the importance of post-transcriptional modifiers of histones in neoplastic stem cells, whose clonal growth sustains aberrant myelopoiesis and expansion of pre-leukemic clones in PMF.

12 CFR 714.8 - Are the early payment provisions, or interest rate provisions, applicable in leasing arrangements?

Code of Federal Regulations, 2010 CFR

2010-01-01

... provisions, or interest rate provisions, applicable in leasing arrangements? You are not subject to the early... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Are the early payment provisions, or interest rate provisions, applicable in leasing arrangements? 714.8 Section 714.8 Banks and Banking NATIONAL...

The hippocampal physiology of approaching middle-age: early indicators of change.

PubMed

Huxter, John R; Miranda, Jason A; Dias, Rebecca

2012-09-01

Age-related cognitive decline presents serious lifestyle challenges, and anatomical changes to the hippocampus are often implicated in clinical conditions later in life. However, relatively little is known about how hippocampal physiology is altered in the transition to middle-age, when early detection may offer the best opportunity for successful treatment. High-yield extracellular recording is a powerful tool for understanding brain function in freely moving animals at single-cell resolution and with millisecond precision. We used this technique to characterize changes to hippocampal physiology associated with maturation in 35-week-old rats. Combining a series of behavioral tasks with recordings of large numbers of neurons, local field potentials (LFP), and network patterns of activation, we were able to generate a comprehensive picture based on more than 25 different assays for each subject. Notable changes associated with aging included increased firing rates in interneurons, reduced LFP power but increased frequency in the 4-12 Hz theta band, and impairment in hippocampal pattern-separation for different environments. General properties of pyramidal cell firing and spatial map integrity were preserved. There was no impairment in theta phase-precession, experience-dependent place field expansion, or sleep reactivation of waking network patterns. There were however changes in foraging strategy and behavioral responses to the introduction of a novel environment. Taken together the results reveal a diverse pattern of changes which are of increasing relevance in an aging population. They also highlight areas where high-yield electrophysiological assays can be used to provide the sensitivity and throughput required for pre-clinical drug-discovery programs. Copyright © 2012 Wiley Periodicals, Inc.

The continuity of psychopathology from early childhood to preadolescence: a prospective cohort study of 3-12-year-old children.

PubMed

Pihlakoski, Leena; Sourander, Andre; Aromaa, Minna; Rautava, Päivi; Helenius, Hans; Sillanpää, Matti

2006-10-01

To study the continuity of psychopathology from the age of 3-12 years. In a population-based birth cohort, children's emotional and behavioral problems were assessed at age 3 using the Child Behavior Checklist 2-3 (CBCL 2-3), and at age 12 by parents using the CBCL 11-18, and the Youth Self Report (YSR) completed by the children. Behavioral ratings were obtained from 800 subjects at both time points. externalizing problems at age 3 predicted both externalizing and internalizing problems among both genders in preadolescence. In girls, internalizing behavior at age 3 predicted parent-reported internalizing behavior, and associated negatively with externalizing behavior in self-reports at age 12. Aggressive behavior was found to be remarkably stable, and both aggressive and destructive behavior independently predicted a wide range of later externalizing and internalizing problems. Parent ratings of withdrawal showed stability from early childhood to preadolescence in both genders. Somatic complaints of 3-year-old girls independently predicted both externalizing and internalizing problems. The results show the complexity of pathways in psychopathology from early childhood to preadolescence. In particular, aggressive and destructive behaviors in very early childhood predict later problems and necessitate early recognition and possible intervention at an early age. An instrument like the CBCL 2-3 is valuable in the early detection of children at risk of long-term problems.

12 CFR 5.51 - Changes in directors and senior executive officers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Changes in directors and senior executive... in directors and senior executive officers. (a) Authority. 12 U.S.C. 1831i. (b) Scope. This section describes the circumstances when a national bank must notify the OCC of a change in its directors and senior...

Early Action on HFCs Mitigates Future Atmospheric Change

NASA Technical Reports Server (NTRS)

Hurwitz, Margaret M.; Fleming, Eric L.; Newman, Paul A.; Li, Feng; Liang, Qing

2017-01-01

As countries take action to mitigate global warming, both by ratifying the UNFCCC Paris Agreement and enacting the Kigali Amendment to the Montreal Protocol to manage hydrofluorocarbons (HFCs), it is important to consider the relative importance of the pertinent greenhouse gases (GHGs), the distinct structure of their atmospheric impacts, and how the timing of potential GHG regulations would affect future changes in atmospheric temperature and ozone. Chemistry-climate model simulations demonstrate that HFCs could contribute substantially to anthropogenic climate change by the mid-21st century, particularly in the upper troposphere and lower stratosphere i.e., global average warming up to 0.19K at 80hPa. Three HFC mitigation scenarios demonstrate the benefits of taking early action in avoiding future atmospheric change: more than 90 of the climate change impacts of HFCs can be avoided if emissions stop by 2030.

Early Action on HFCs Mitigates Future Atmospheric Change

NASA Astrophysics Data System (ADS)

Hurwitz, Margaret; Fleming, Eric; Newman, Paul; Li, Feng; Liang, Qing

2017-04-01

As countries take action to mitigate global warming, both by ratifying the UNFCCC Paris Agreement and enacting the Kigali Amendment to the Montreal Protocol to manage hydrofluorocarbons (HFCs), it is important to consider the relative importance of the pertinent greenhouse gases (GHGs), the distinct structure of their atmospheric impacts, and how the timing of potential GHG regulations would affect future changes in atmospheric temperature and ozone. Chemistry-climate model simulations demonstrate that HFCs could contribute substantially to anthropogenic climate change by the mid-21st century, particularly in the upper troposphere and lower stratosphere i.e., global average warming up to 0.19K at 80hPa. Three HFC mitigation scenarios demonstrate the benefits of taking early action in avoiding future atmospheric change: more than 90% of the climate change impacts of HFCs can be avoided if emissions stop by 2030.

The PAX2-null immunophenotype defines multiple lineages with common expression signatures in benign and neoplastic oviductal epithelium

PubMed Central

Ning, Gang; Bijron, Jonathan G.; Yamamoto, Yusuke; Wang, Xia; Howitt, Brooke E.; Herfs, Michael; Yang, Eric; Hong, Yue; Cornille, Maxence; Wu, Lingyan; Hanamornroongruang, Suchanan; McKeon, Frank D.; Crum, Christopher P.; Xian, Wa

2014-01-01

neoplastic entities links normal progenitor cell expansion to abnormal and neoplastic outgrowth in the oviduct and exposes a common pathway that could be a target for early prevention. PMID:25130537

Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia.

PubMed

Lee, Hye Mi; Kwon, Kyum-Yil; Kim, Min-Jik; Jang, Ji-Wan; Suh, Sang-Il; Koh, Seong-Beom; Kim, Ji Hyun

2014-06-01

Previous MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage. We recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively. Voxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p < 0.05). Vertex-based shape analysis showed regionally contracted area on the posterolateral and ventromedial putamen bilaterally in PD patients (corrected p < 0.05). No correlations were found between cortical and subcortical grey matter and clinical variables representing disease duration and severity. Our results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cranial thickness changes in early childhood

NASA Astrophysics Data System (ADS)

Gajawelli, Niharika; Deoni, Sean; Shi, Jie; Dirks, Holly; Linguraru, Marius George; Nelson, Marvin D.; Wang, Yalin; Lepore, Natasha

2017-11-01

The neurocranium changes rapidly in early childhood to accommodate the developing brain. However, developmental disorders may cause abnormal growth of the neurocranium, the most common one being craniosynostosis, affecting about 1 in 2000 children. It is important to understand how the brain and neurocranium develop together to understand the role of the neurocranium in neurodevelopmental outcomes. However, the neurocranium is not as well studied as the human brain in early childhood, due to a lack of imaging data. CT is typically employed to investigate the cranium, but, due to ionizing radiation, may only be used for clinical cases. However, the neurocranium is also visible on magnetic resonance imaging (MRI). Here, we used a large dataset of MRI images from healthy children in the age range of 1 to 2 years old and extracted the neurocranium. A conformal geometry based analysis pipeline is implemented to determine a set of statistical atlases of the neurocranium. A growth model of the neurocranium will help us understand cranial bone and suture development with respect to the brain, which will in turn inform better treatment strategies for neurocranial disorders.

Cool Science: K-12 Climate Change Art Displayed on Buses

NASA Astrophysics Data System (ADS)

Chen, R. F.; Lustick, D. S.; Lohmeier, J.; Thompson, S. R.

2015-12-01

Cool science is an art contest where K12 students create placards (7" x 22") to educate the public about climate change. Students are prompted to create their artwork in response to questions such as: What is the evidence for climate change? How does climate change impact your local community? What can you do to reduce the impacts of climate change? In each of three years, 500-600 student entrees have been submitted from more than 12 school districts across Massachusetts. A panel of judges including scientists, artists, rapid transit representatives, and educators chooses elementary, middle, and high school winners. Winners (6), runners-up (6), and honorable mentions (12) and their families and teachers are invited to an annual Cool Science Award Ceremony to be recognized and view winning artwork. All winning artwork is posted on the Cool Science website. The winning artwork (2 per grade band) is converted into placards (11" x 28") and posters (2.5' x 12') that are placed on the inside (placards) and outside (posters) of buses. Posters are displayed for one month. So far, Cool Science was implemented in Lowell, MA where over 5000 public viewers see the posters daily on the sides of Lowell Rapid Transit Authority (LRTA) buses, making approximately 1,000,000 impressions per year. Cool Science acts to increase climate literacy in children as well as the public, and as such promotes intergenerational learning. Using art in conjunction with science learning about climate change appears to be effective at engaging not just traditionally high achieving science students, but also those interested in the creative arts. Hearing winners' stories about how they created their artwork and what this contest meant to them supports the idea that Cool Science attracts a wide diversity of students. Parents discuss climate change with their children. Multiple press releases announcing the winners further promotes the awareness of climate change throughout school districts and their

Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants

PubMed Central

Buchanan, Adam H; Manickam, Kandamurugu; Meyer, Michelle N; Wagner, Jennifer K; Hallquist, Miranda L G; Williams, Janet L; Rahm, Alanna Kulchak; Williams, Marc S; Chen, Zong-Ming E; Shah, Chaitali K; Garg, Tullika K; Lazzeri, Amanda L; Schwartz, Marci L B; Lindbuchler, D'Andra M; Fan, Audrey L; Leeming, Rosemary; Servano, Pedro O; Smith, Ashlee L; Vogel, Victor G; Abul-Husn, Noura S; Dewey, Frederick E; Lebo, Matthew S; Mason-Suares, Heather M; Ritchie, Marylyn D; Davis, F Daniel; Carey, David J; Feinberg, David T; Faucett, W Andrew; Ledbetter, David H; Murray, Michael F

2018-01-01

Purpose The clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility. Methods Whole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient–participants and their clinicians. We queried patient–participants’ electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient–participants of eligible age who had begun risk management. Results Thirty-seven MyCode patient–participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer—including a stage 1C fallopian tube cancer—via these procedures. Conclusion Screening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility. PMID:29261187

Climate Change Decouples Drought from Early Wine Grape Harvests in France

NASA Technical Reports Server (NTRS)

Cook, Benjamin I.; Wolkovich, Elizabeth M.

2016-01-01

Across the world, wine grape phenology has advanced in recent decades, in step with climate-change-induced trends in temperature - the main driver of fruit maturation - and drought. Fully understanding how climate change contributes to changes in harvest dates, however, requires analysing wine grape phenology and its relationship to climate over a longer-term context, including data predating anthropogenic interference in the climate system. Here, we investigate the climatic controls of wine grape harvest dates from 1600-2007 in France and Switzerland using historical harvest and climate data. Early harvests occur with warmer temperatures (minus 6 days per degree Centigrade) and are delayed by wet conditions (plus 0.07 days per millimeter; plus 1.68 days per PDSI (Palmer drought severity index)) during spring and summer. In recent decades (1981-2007), however, the relationship between harvest timing and drought has broken down. Historically, high summer temperatures in Western Europe, which would hasten fruit maturation, required drought conditions to generate extreme heat. The relationship between drought and temperature in this region, however, has weakened in recent decades and enhanced warming from anthropogenic greenhouse gases can generate the high temperatures needed for early harvests without drought. Our results suggest that climate change has fundamentally altered the climatic drivers of early wine grape harvests in France, with possible ramifications for viticulture management and wine quality.

Forests and Phenology: Designing the Early Warning System to Understand Forest Change

NASA Astrophysics Data System (ADS)

Pierce, T.; Phillips, M. B.; Hargrove, W. W.; Dobson, G.; Hicks, J.; Hutchins, M.; Lichtenstein, K.

2010-12-01

Vegetative phenology is the study of plant development and changes with the seasons, such as the greening-up and browning-down of forests, and how these events are influenced by variations in climate. A National Phenology Data Set, based on Moderate Resolution Imaging Spectroradiometer satellite images covering 2002 through 2009, is now available from work by NASA, the US Forest Service, and Oak Ridge National Laboratory. This new data set provides an easily interpretable product useful for detecting changes to the landscape due to long-term factors such as climate change, as well as finding areas affected by short-term forest threats such as insects or disease. The Early Warning System (EWS) is a toolset being developed by the US Forest Service and the University of North Carolina-Asheville to support distribution and use of the National Phenology Data Set. The Early Warning System will help research scientists, US Forest Service personnel, forest and natural resources managers, decision makers, and the public in the use of phenology data to better understand unexpected change within our nation’s forests. These changes could have multiple natural sources such as insects, disease, or storm damage, or may be due to human-induced events, like thinning, harvest, forest conversion to agriculture, or residential and commercial use. The primary goal of the Early Warning System is to provide a seamless integration between monitoring, detection, early warning and prediction of these forest disturbances as observed through phenological data. The system consists of PC and web-based components that are structured to support four user stages of increasing knowledge and data sophistication. Building Literacy: This stage of the Early Warning System educates potential users about the system, why the system should be used, and the fundamentals about the data the system uses. The channels for this education include a website, interactive tutorials, pamphlets, and other technology

3D quantitative analysis of early decomposition changes of the human face.

PubMed

Caplova, Zuzana; Gibelli, Daniele Maria; Poppa, Pasquale; Cummaudo, Marco; Obertova, Zuzana; Sforza, Chiarella; Cattaneo, Cristina

2018-03-01

Decomposition of the human body and human face is influenced, among other things, by environmental conditions. The early decomposition changes that modify the appearance of the face may hamper the recognition and identification of the deceased. Quantitative assessment of those changes may provide important information for forensic identification. This report presents a pilot 3D quantitative approach of tracking early decomposition changes of a single cadaver in controlled environmental conditions by summarizing the change with weekly morphological descriptions. The root mean square (RMS) value was used to evaluate the changes of the face after death. The results showed a high correlation (r = 0.863) between the measured RMS and the time since death. RMS values of each scan are presented, as well as the average weekly RMS values. The quantification of decomposition changes could improve the accuracy of antemortem facial approximation and potentially could allow the direct comparisons of antemortem and postmortem 3D scans.

Correlation between standardized uptake value and apparent diffusion coefficient of neoplastic lesions evaluated with whole-body simultaneous hybrid PET/MRI.

PubMed

Rakheja, Rajan; Chandarana, Hersh; DeMello, Linda; Jackson, Kimberly; Geppert, Christian; Faul, David; Glielmi, Christopher; Friedman, Kent P

2013-11-01

The purpose of this study was to assess the correlation between standardized uptake value (SUV) and apparent diffusion coefficient (ADC) of neoplastic lesions in the use of a simultaneous PET/MRI hybrid system. Twenty-four patients with known primary malignancies underwent FDG PET/CT. They then underwent whole-body PET/MRI. Diffusion-weighted imaging was performed with free breathing and a single-shot spin-echo echo-planar imaging sequence with b values of 0, 350, and 750 s/mm(2). Regions of interest were manually drawn along the contours of neoplastic lesions larger than 1 cm, which were clearly identified on PET and diffusion-weighted images. Maximum SUV (SUVmax) on PET/MRI and PET/CT images, mean SUV (SUVmean), minimum ADC (ADCmin), and mean ADC (ADCmean) were recorded on PET/MR images for each FDG-avid neoplastic soft-tissue lesion with a maximum of three lesions per patient. Pearson correlation coefficient was used to asses the following relations: SUVmax versus ADCmin on PET/MR and PET/CT images, SUVmean versus ADCmean, and ratio of SUVmax to mean liver SUV (SUV ratio) versus ADCmin. A subanalysis of patients with progressive disease versus partial treatment response was performed with the ratio of SUVmax to ADCmin for the most metabolically active lesion. Sixty-nine neoplastic lesions (52 nonosseous lesions, 17 bone metastatic lesions) were evaluated. The mean SUVmax from PET/MRI was 7.0 ± 6.0; SUVmean, 5.6 ± 4.6; mean ADCmin, 1.10 ± 0.58; and mean ADCmean, 1.48 ± 0.72. A significant inverse Pearson correlation coefficient was found between PET/MRI SUVmax and ADCmin (r = -0.21, p = 0.04), between SUVmean and ADCmean (r = -0.18, p = 0.07), and between SUV ratio and ADCmin (r = -0.27, p = 0.01). A similar inverse Pearson correlation coefficient was found between the PET/CT SUVmax and ADCmin. Twenty of 24 patients had previously undergone PET/CT; five patients had a partial treatment response, and six had progressive disease according to Response Evaluation

Protein p16 as a marker of dysplastic and neoplastic alterations in cervical epithelial cells

PubMed Central

Volgareva, Galina; Zavalishina, Larisa; Andreeva, Yulia; Frank, Georgy; Krutikova, Ella; Golovina, Darya; Bliev, Alexander; Spitkovsky, Dimitry; Ermilova, Valeriya; Kisseljov, Fjodor

2004-01-01

Background Cervical carcinomas are second most frequent type of women cancer. Success in diagnostics of this disease is due to the use of Pap-test (cytological smear analysis). However Pap-test gives significant portion of both false-positive and false-negative conclusions. Amendments of the diagnostic procedure are desirable. Aetiological role of papillomaviruses in cervical cancer is established while the role of cellular gene alterations in the course of tumor progression is less clear. Several research groups including us have recently named the protein p16INK4a as a possible diagnostic marker of cervical cancer. To evaluate whether the specificity of p16INK4a expression in dysplastic and neoplastic cervical epithelium is sufficient for such application we undertook a broader immunochistochemical registration of this protein with a highly p16INK4a-specific monoclonal antibody. Methods Paraffin-embedded samples of diagnostic biopsies and surgical materials were used. Control group included vaginal smears of healthy women and biopsy samples from patients with cervical ectopia. We examined 197 samples in total. Monoclonal antibody E6H4 (MTM Laboratories, Germany) was used. Results In control samples we did not find any p16INK4a-positive cells. Overexpression of p16INK4a was detected in samples of cervical dysplasia (CINs) and carcinomas. The portion of p16INK4a-positive samples increased in the row: CIN I – CIN II – CIN III – invasive carcinoma. For all stages the samples were found to be heterogeneous with respect to p16INK4a-expression. Every third of CINs III and one invasive squamous cell carcinoma (out of 21 analyzed) were negative. Conclusions Overexpression of the protein p16INK4a is typical for dysplastic and neoplastic epithelium of cervix uteri. However p16INK4a-negative CINs and carcinomas do exist. All stages of CINs and carcinomas analyzed are heterogeneous with respect to p16INK4a expression. So p16INK4a-negativity is not a sufficient reason to

Targeting Sphingosine Kinase Isoforms Effectively Reduces Growth and Survival of Neoplastic Mast Cells With D816V-KIT

PubMed Central

Bandara, Geethani; Muñoz-Cano, Rosa; Tobío, Araceli; Yin, Yuzhi; Komarow, Hirsh D.; Desai, Avanti; Metcalfe, Dean D.; Olivera, Ana

2018-01-01

Mastocytosis is a disorder resulting from an abnormal mast cell (MC) accumulation in tissues that is often associated with the D816V mutation in KIT, the tyrosine kinase receptor for stem cell factor. Therapies available to treat aggressive presentations of mastocytosis are limited, thus exploration of novel pharmacological targets that reduce MC burden is desirable. Since increased generation of the lipid mediator sphingosine-1-phosphate (S1P) by sphingosine kinase (SPHK) has been linked to oncogenesis, we studied the involvement of the two SPHK isoforms (SPHK1 and SPHK2) in the regulation of neoplastic human MC growth. While SPHK2 inhibition prevented entry into the cell cycle in normal and neoplastic human MCs with minimal effect on cell survival, SPHK1 inhibition caused cell cycle arrest in G2/M and apoptosis, particularly in D816V-KIT MCs. This was mediated via activation of the DNA damage response (DDR) cascade, including phosphorylation of the checkpoint kinase 2 (CHK2), CHK2-mediated M-phase inducer phosphatase 3 depletion, and p53 activation. Combination treatment of SPHK inhibitors with KIT inhibitors showed greater growth inhibition of D816V-KIT MCs than either inhibitor alone. Furthermore, inhibition of SPHK isoforms reduced the number of malignant bone marrow MCs from patients with mastocytosis and the growth of D816V-KIT MCs in a xenograft mouse model. Our results reveal a role for SPHK isoforms in the regulation of growth and survival in normal and neoplastic MCs and suggest a regulatory function for SPHK1 in the DDR in MCs with KIT mutations. The findings also suggest that targeting the SPHK/S1P axis may provide an alternative to tyrosine kinase inhibitors, alone or in combination, for the treatment of aggressive mastocytosis and other hematological malignancies associated with the D816V-KIT mutation. PMID:29643855

Targeting Sphingosine Kinase Isoforms Effectively Reduces Growth and Survival of Neoplastic Mast Cells With D816V-KIT.

PubMed

Bandara, Geethani; Muñoz-Cano, Rosa; Tobío, Araceli; Yin, Yuzhi; Komarow, Hirsh D; Desai, Avanti; Metcalfe, Dean D; Olivera, Ana

2018-01-01

Mastocytosis is a disorder resulting from an abnormal mast cell (MC) accumulation in tissues that is often associated with the D816V mutation in KIT, the tyrosine kinase receptor for stem cell factor. Therapies available to treat aggressive presentations of mastocytosis are limited, thus exploration of novel pharmacological targets that reduce MC burden is desirable. Since increased generation of the lipid mediator sphingosine-1-phosphate (S1P) by sphingosine kinase (SPHK) has been linked to oncogenesis, we studied the involvement of the two SPHK isoforms (SPHK1 and SPHK2) in the regulation of neoplastic human MC growth. While SPHK2 inhibition prevented entry into the cell cycle in normal and neoplastic human MCs with minimal effect on cell survival, SPHK1 inhibition caused cell cycle arrest in G2/M and apoptosis, particularly in D816V-KIT MCs. This was mediated via activation of the DNA damage response (DDR) cascade, including phosphorylation of the checkpoint kinase 2 (CHK2), CHK2-mediated M-phase inducer phosphatase 3 depletion, and p53 activation. Combination treatment of SPHK inhibitors with KIT inhibitors showed greater growth inhibition of D816V-KIT MCs than either inhibitor alone. Furthermore, inhibition of SPHK isoforms reduced the number of malignant bone marrow MCs from patients with mastocytosis and the growth of D816V-KIT MCs in a xenograft mouse model. Our results reveal a role for SPHK isoforms in the regulation of growth and survival in normal and neoplastic MCs and suggest a regulatory function for SPHK1 in the DDR in MCs with KIT mutations. The findings also suggest that targeting the SPHK/S1P axis may provide an alternative to tyrosine kinase inhibitors, alone or in combination, for the treatment of aggressive mastocytosis and other hematological malignancies associated with the D816V-KIT mutation.

Study designs to investigate Nox1 acceleration of neoplastic progression in immortalized human epithelial cells by selection of differentiation resistant cells.

PubMed

Sattayakhom, Apsorn; Chunglok, Warangkana; Ittarat, Wanida; Chamulitrat, Walee

2014-01-01

To investigate the role of NADPH oxidase homolog Nox1 at an early step of cell transformation, we utilized human gingival mucosal keratinocytes immortalized by E6/E7 of human papillomavirus (HPV) type 16 (GM16) to generate progenitor cell lines either by chronic ethanol exposure or overexpression with Nox1. Among several cobblestone epithelial cell lines obtained, two distinctive spindle cell lines - FIB and NuB1 cells were more progressively transformed exhibiting tubulogenesis and anchorage-independent growth associated with increased invasiveness. These spindle cells acquired molecular markers of epithelial mesenchymal transition (EMT) including mesenchymal vimentin and simple cytokeratins (CK) 8 and 18 as well as myogenic alpha-smooth muscle actin and caldesmon. By overexpression and knockdown experiments, we showed that Nox1 on a post-translational level regulated the stability of CK18 in an ROS-, phosphorylation- and PKCepilon-dependent manner. PKCepilon may thus be used as a therapeutic target for EMT inhibition. Taken together, Nox1 accelerates neoplastic progression by regulating structural intermediate filaments leading to EMT of immortalized human gingival epithelial cells.

DEVELOPMENTAL CHANGES IN SEROTONIN SIGNALING: IMPLICATIONS FOR EARLY BRAIN FUNCTION, BEHAVIOR AND ADAPTATION

PubMed Central

BRUMMELTE, S.; GLANAGHY, E. MC; BONNIN, A.; OBERLANDER, T. F.

2017-01-01

The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as ‘plasticity’ rather than ‘risk’ factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk. PMID:26905950

Does early change predict long-term (6 months) improvements in subjects who receive manual therapy for low back pain?

PubMed

Cook, Chad; Petersen, Shannon; Donaldson, Megan; Wilhelm, Mark; Learman, Ken

2017-09-01

Early change is commonly assessed for manual therapy interventions and has been used to determine treatment appropriateness. However, current studies have only explored the relationship of between or within-session changes and short-/medium-term outcomes. The goal of this study was to determine whether pain changes after two weeks of pragmatic manual therapy could predict those participants with chronic low back pain who demonstrate continued improvements at 6-month follow-up. This study was a retrospective observational design. Univariate logistic regression analyses were performed using a 33% and a 50% pain change to predict improvement. Those who experienced a ≥33% pain reduction by 2 weeks had 6.98 (95% CI = 1.29, 37.53) times higher odds of 50% improvement on the GRoC and 4.74 (95% CI = 1.31, 17.17) times higher odds of 50% improvement on the ODI (at 6 months). Subjects who reported a ≥50% pain reduction at 2 weeks had 5.98 (95% CI = 1.56, 22.88) times higher odds of a 50% improvement in the GRoC and 3.99 (95% CI = 1.23, 12.88) times higher odds of a 50% improvement in the ODI (at 6 months). Future studies may investigate whether a change in plan of care is beneficial for patients who are not showing early improvement predictive of a good long-term outcome.

Effects of Training and Feedback on Accuracy of Predicting Rectosigmoid Neoplastic Lesions and Selection of Surveillance Intervals by Endoscopists Performing Optical Diagnosis of Diminutive Polyps.

PubMed

Vleugels, Jasper L A; Dijkgraaf, Marcel G W; Hazewinkel, Yark; Wanders, Linda K; Fockens, Paul; Dekker, Evelien

2018-05-01

Real-time differentiation of diminutive polyps (1-5 mm) during endoscopy could replace histopathology analysis. According to guidelines, implementation of optical diagnosis into routine practice would require it to identify rectosigmoid neoplastic lesions with a negative predictive value (NPV) of more than 90%, using histologic findings as a reference, and agreement with histology-based surveillance intervals for more than 90% of cases. We performed a prospective study with 39 endoscopists accredited to perform colonoscopies on participants with positive results from fecal immunochemical tests in the Bowel Cancer Screening Program at 13 centers in the Netherlands. Endoscopists were trained in optical diagnosis using a validated module (Workgroup serrAted polypS and Polyposis). After meeting predefined performance thresholds in the training program, the endoscopists started a 1-year program (continuation phase) in which they performed narrow band imaging analyses during colonoscopies of participants in the screening program and predicted histological findings with confidence levels. The endoscopists were randomly assigned to groups that received feedback or no feedback on the accuracy of their predictions. Primary outcome measures were endoscopists' abilities to identify rectosigmoid neoplastic lesions (using histology as a reference) with NPVs of 90% or more, and selecting surveillance intervals that agreed with those determined by histology for at least 90% of cases. Of 39 endoscopists initially trained, 27 (69%) completed the training program. During the continuation phase, these 27 endoscopists performed 3144 colonoscopies in which 4504 diminutive polyps were removed. The endoscopists identified neoplastic lesions with a pooled NPV of 90.8% (95% confidence interval 88.6-92.6); their proposed surveillance intervals agreed with those determined by histologic analysis for 95.4% of cases (95% confidence interval 94.0-96.6). Findings did not differ between the group

Clinical factors analysis of curative effect of focused ultrasound treatment for non neoplastic epithelial disorders of vulva.

PubMed

Sun, Xin; Xue, Min; Deng, Xinliang; Wan, Yajun

2010-09-01

To explore the related factors to influence the curative effect of focused ultrasound treatment for non neoplastic epithelial disorders of vulva. A total of 382 patients with non neoplastic epithelial disorders of vulva were included in this study and treated by focused ultrasound. During and after the treatment, the symptoms and physical signs of the subjects were observed, and the efficacy was evaluated. We analyzed the relation between pathologic type, age, course, area, or itch degree and curative effect. Symptoms of all patients were relieved, and appearance and color of the vulva became normal after the ultrasound treatment, with a total effective rate of 99.74%. The cure ratios of patients with different pathologic types, ages, courses, areas, and itch degrees were significantly different (χ(2)=9.58, P<0.01; χ(2)=22.385, P<0.01; χ(2)=32.260, P<0.01; χ(2)=57.99,P<0.01; χ(2)=42.13,P<0.01, respectively). Focused ultrasound treatment is safe and effective for the nonneoplastic epithelial disorders of the vulva and the efficacy is associated with the pathologic type, age, course, area, and itch degree.

Some ways in which neighborhoods, nuclear families, friendship groups, and schools jointly affect changes in early adolescent development.

PubMed

Cook, Thomas D; Herman, Melissa R; Phillips, Meredith; Settersten, Richard A

2002-01-01

This study assessed some ways in which schools, neighborhoods, nuclear families, and friendship groups jointly contribute to positive change during early adolescence. For each context, existing theory was used to develop a multiattribute index that should promote successful development. Descriptive analyses showed that the four resulting context indices were only modestly intercorrelated at the individual student level (N = 12,398), but clustered more tightly at the school and neighborhood levels (N = 23 and 151 respectively). Only for aggregated units did knowing the developmental capacity of any one context strongly predict the corresponding capacity of the other contexts. Analyses also revealed that each context facilitated individual change in a success index that tapped into student academic performance, mental health, and social behavior. However, individual context effects were only modest in size over the 19 months studied and did not vary much by context. The joint influence of all four contexts was cumulatively large, however, and because it was generally additive in form, no constellation of contexts was identified whose total effect reliably surpassed the sum of its individual context main effects. These results suggest that achieving significant population changes in multidimensional student growth during early adolescence most likely requires both theory and interventions that are explicitly pan-contextual.

In Vitro Progression of HPV16 Episome-Associated Cervical Neoplasia Displays Fundamental Similarities to Integrant-Associated Carcinogenesis

PubMed Central

Gray, Elizabeth; Pett, Mark R.; Ward, Dawn; Winder, David M.; Stanley, Margaret A.; Roberts, Ian; Scarpini, Cinzia G.; Coleman, Nicholas

2010-01-01

An important event in the development of cervical squamous cell carcinoma (SCC) is deregulated expression of high-risk human papillomavirus (HR-HPV) oncogenes, most commonly related to viral integration into host DNA. Mechanisms of development of the ~15% of SCCs that contain extra-chromosomal (episomal) HR-HPV are poorly understood, due to limited longitudinal data. We therefore employed the W12 model to study mechanisms of cervical carcinogenesis associated with episomal HPV16. In vitro progression of W12 normally occurs through selection of cells containing integrated HPV16. However, in one long-term culture, keratinocytes developed a selective growth advantage and invasive phenotype, while retaining HPV16 episomes at increased copy number in the absence of transcriptionally active integrants. Longitudinal investigations revealed similarities between the episome- and integrant-associated routes of neoplastic progression. Most notable were dynamic changes in viral early gene expression in episome-retaining cells, consistent with continually changing selective pressures. An early increase in viral transcription preceded elevated episome copy number and was followed by a reduction to near baseline after the development of invasiveness. Episomal transcriptional deregulation did not require selection of a specific sequence variant of the HPV16 upstream regulatory region, although increased levels of acetylated histone H4 around the late promoter implicated a role for altered chromatin structure. Interestingly, invasive episome-retaining cells demonstrated high levels of HPV16-E2/E6 proteins (despite decreased transcript levels) and reduced expression of interferon-stimulated genes, adaptations that support viral persistence and cell survival. Our findings suggest a unified working model for events important in cervical neoplastic progression, regardless of HR-HPV physical state. PMID:20442284

A comparison between the clinical significance and growth mixture modelling early change methods at predicting negative outcomes.

PubMed

Flood, Nicola; Page, Andrew; Hooke, Geoff

2018-05-03

Routine outcome monitoring benefits treatment by identifying potential no change and deterioration. The present study compared two methods of identifying early change and their ability to predict negative outcomes on self-report symptom and wellbeing measures. 1467 voluntary day patients participated in a 10-day group Cognitive Behaviour Therapy (CBT) program and completed the symptom and wellbeing measures daily. Early change, as defined by (a) the clinical significance method and (b) longitudinal modelling, was compared on each measure. Early change, as defined by the simpler clinical significance method, was superior at predicting negative outcomes than longitudinal modelling. The longitudinal modelling method failed to detect a group of deteriorated patients, and agreement between the early change methods and the final unchanged outcome was higher for the clinical significance method. Therapists could use the clinical significance early change method during treatment to alert them of patients at risk for negative outcomes, which in turn could allow therapists to prevent those negative outcomes from occurring.

12 CFR 333.2 - Change in general character of business.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Change in general character of business. 333.2... GENERAL POLICY EXTENSION OF CORPORATE POWERS Regulations § 333.2 Change in general character of business... permit any change to be made in the general character or type of business exercised by it after the...

Early action on HFCs mitigates future atmospheric change

NASA Astrophysics Data System (ADS)

Hurwitz, Margaret M.; Fleming, Eric L.; Newman, Paul A.; Li, Feng; Liang, Qing

2016-11-01

As countries take action to mitigate global warming, both by ratifying the UNFCCC Paris Agreement and enacting the Kigali Amendment to the Montreal Protocol to manage hydrofluorocarbons (HFCs), it is important to consider the relative importance of the pertinent greenhouse gases and the distinct structure of their atmospheric impacts, and how the timing of potential greenhouse gas regulations would affect future changes in atmospheric temperature and ozone. HFCs should be explicitly considered in upcoming climate and ozone assessments, since chemistry-climate model simulations demonstrate that HFCs could contribute substantially to anthropogenic climate change by the mid-21st century, particularly in the upper troposphere and lower stratosphere i.e., global average warming up to 0.19 K at 80 hPa. The HFC mitigation scenarios described in this study demonstrate the benefits of taking early action in avoiding future atmospheric change: more than 90% of the climate change impacts of HFCs can be avoided if emissions stop by 2030.

Early Action on Hfcs Mitigates Future Atmospheric Change

NASA Technical Reports Server (NTRS)

Hurwitz, Margaret M.; Fleming, Eric L.; Newman, Paul A.; Li, Feng; Liang, Qing

2016-01-01

As countries take action to mitigate global warming, both by ratifying theUNFCCCParis Agreement and enacting the Kigali Amendment to the Montreal Protocol to manage hydrofluorocarbons (HFCs), it is important to consider the relative importance of the pertinent greenhouse gases and the distinct structure of their atmospheric impacts, and how the timing of potential greenhouse gas regulations would affect future changes in atmospheric temperature and ozone. HFCs should be explicitly considered in upcoming climate and ozone assessments, since chemistry-climate model simulations demonstrate that HFCs could contribute substantially to anthropogenic climate change by the mid- 21st century, particularly in the upper troposphere and lower stratosphere i.e., global average warming up to 0.19 Kat 80 hPa. The HFCmitigation scenarios described in this study demonstrate the benefits of taking early action in avoiding future atmospheric change: more than 90% of the climate change impacts of HFCs can be avoided if emissions stop by 2030.

Screening colonoscopy for the detection of neoplastic lesions in asymptomatic HIV-infected subjects.

PubMed

Bini, E J; Green, B; Poles, M A

2009-08-01

Although non-AIDS defining malignancies are rapidly increasing as HIV-infected subjects live longer, little is know about the results of screening for colonic neoplasms (adenomatous polyps and adenocarcinomas) in this population. We conducted a screening colonoscopy study to determine the prevalence of colonic neoplasms in 136 asymptomatic HIV-infected subjects >or=50 years of age and 272 asymptomatic uninfected control subjects matched for age, sex, and family history of colorectal cancer. Advanced neoplasms were defined as adenomas >or=10 mm or any adenoma, regardless of size, with villous histology, high-grade dysplasia, or adenocarcinoma. The prevalence of neoplastic lesions was significantly higher in HIV-infected subjects than in control subjects (62.5% vs 41.2%, p<0.001), and remained highly significant after adjustment for potential confounding variables (odds ratio = 3.00; 95% confidence interval, 1.83 to 4.93). Among patients with colorectal adenocarcinoma, HIV-infected subjects were significantly younger (52.4 (SD 1.3) vs 60.3 (SD 4.0) years, p = 0.002) and were more likely to have advanced cancers (stage III or IV) than control subjects (60.0% vs 16.7%, p = 0.24). Of HIV-infected subjects with advanced neoplasms proximal to the splenic flexure, distal neoplastic lesions were absent in 88.9% of individuals and these would have been missed by flexible sigmoidoscopy. HIV-infected subjects have a higher prevalence of colonic neoplasms, and adenocarcinomas develop at a younger age and are more advanced than in uninfected subjects. Our findings suggest that screening colonoscopy should be offered to HIV-infected subjects, but the age of initiation and the optimal frequency of screening require further study.

Active Early: one-year policy intervention to increase physical activity among early care and education programs in Wisconsin.

PubMed

LaRowe, Tara L; Tomayko, Emily J; Meinen, Amy M; Hoiting, Jill; Saxler, Courtney; Cullen, Bridget

2016-07-20

Early childcare and education (ECE) is a prime setting for obesity prevention and the establishment of healthy behaviors. The objective of this quasi-experimental study was to examine the efficacy of the Active Early guide, which includes evidenced-based approaches, provider resources, and training, to improve physical activity opportunities through structured (i.e. teacher-led) activity and environmental changes thereby increasing physical activity among children, ages 2-5 years, in the ECE setting. Twenty ECE programs in Wisconsin, 7 family and 13 group, were included. An 80-page guide, Active Early, was developed by experts and statewide partners in the fields of ECE, public health, and physical activity and was revised by ECE providers prior to implementation. Over 12 months, ECE programs received on-site training and technical assistance to implement the strategies and resources provided in the Active Early guide. Main outcome measures included observed minutes of teacher-led physical activity, physical activity environment measured by the Environment and Policy Assessment and Observation (EPAO) instrument, and child physical activity levels via accelerometry. All measures were collected at baseline, 6 months, and 12 months and were analyzed for changes over time. Observed teacher-led physical activity significantly increased from 30.9 ± 22.7 min at baseline to 82.3 ± 41.3 min at 12 months. The change in percent time children spent in sedentary activity decreased significantly after 12 months (-4.4 ± 14.2 % time, -29.2 ± 2.6 min, p < 0.02). Additionally, as teacher led-activity increased, percent time children were sedentary decreased (r = -0.37, p < 0.05) and percent time spent in light physical activity increased (r = 0.35, p < 0.05). Among all ECE programs, the physical activity environment improved significantly as indicated by multiple sub-scales of the EPAO; scores showing the greatest increases were the

Histiocyte-like cells expressing factor XIIIa do not belong to the neoplastic cell population in malignant fibrous histiocytoma.

PubMed

Szollosi, Zoltan; Nemeth, Tamas; Egervari, Kristof; Nemes, Zoltan

2005-01-01

The term malignant fibrous histiocytoma (MFH) is widely used for pleomorphic soft tissue sarcomas without a specific line of differentiation. MFH is included in the category of fibrohistiocytic soft tissue tumors. MFH has a broad range of histological appearances, and it has several subtypes. All of these subtypes are composed of spindled fibroblast-like cells, undifferentiated cells, and histiocytic or histiocyte-like cells. A large number of fibroblast-like and pleomorphic cells express factor XIIIa in MFH. The cytological pleomorphism of factor XIIIa cells suggests that these cells may belong to the neoplastic population. It is equally possible that the factor XIIIa-positive cells are only activated stromal cells. The relation of factor XIIIa-positive cells to the neoplastic cell population in MFH is addressed in the present study. A morphometric approach compares the measure of nuclear pleomorphism of the factor XIIIa-positive cells with that of the factor XIIIa-negative tumor cells in high-grade MFH. The immunohistochemical approach compares the factor XIIIa-positive and -negative cell populations with regard to mutations of p53 tumor suppressor gene in p53-positive MFH cases. We selected 58 cases of soft tissue pleomorphic or storiform-pleomorphic MFH on the basis of histopathological examinations. A combination of incident light immunofluorescence for factor XIIIa and transmitted light examination for nuclear staining was used for morphometrical analysis. We found cytoplasmic factor XIIIa positivity in at least 2% of cells in 39 cases; the number of factor XIIIa-positive cells was under 0.5% in two cases, and the number of factor-positive cells ranged between 0.5% and 2% in 13 cases. Eighteen cases were analyzed with nuclear morphometry. We found that mean nuclear area and mean nuclear Ferret diameter in factor XIIIa-positive cells differed significantly from those of the tumor cells in all cases. The mean nuclear roundness factor differed significantly only

What Changes Can We Expect? Future Trends Impacting Early Childhood Education

ERIC Educational Resources Information Center

Neugebauer, Roger; Donohue, Chip; Schweinhart, Larry; Milic, Sasa; Martin, Jody

2011-01-01

The author invited some of his friends to give their views regarding key trends that will impact the early childhood world in the coming years. Chip Donohue, Director of Distance Learning, Erikson Institute, Chicago, Illinois, observed that the rapid pace of technology development and deployment has already changed, and will continue to change,…

Early effects of climate change: do they include changes in vector-borne disease?

PubMed Central

Kovats, R S; Campbell-Lendrum, D H; McMichael, A J; Woodward, A; Cox, J S

2001-01-01

The world's climate appears now to be changing at an unprecedented rate. Shifts in the distribution and behaviour of insect and bird species indicate that biological systems are already responding to this change. It is well established that climate is an important determinant of the spatial and temporal distribution of vectors and pathogens. In theory, a change in climate would be expected to cause changes in the geographical range, seasonality (intra-annual variability), and in the incidence rate (with or without changes in geographical or seasonal patterns). The detection and then attribution of such changes to climate change is an emerging task for scientists. We discuss the evidence required to attribute changes in disease and vectors to the early effects of anthropogenic climate change. The literature to date indicates that there is a lack of strong evidence of the impact of climate change on vector-borne diseases (i.e. malaria, dengue, leishmaniasis, tick-borne diseases). New approaches to monitoring, such as frequent and long-term sampling along transects to monitor the full latitudinal and altitudinal range of specific vector species, are necessary in order to provide convincing direct evidence of climate change effects. There is a need to reassess the appropriate levels of evidence, including dealing with the uncertainties attached to detecting the health impacts of global change. PMID:11516383

TGF-beta-induced apoptosis in human thyrocytes is mediated by p27kip1 reduction and is overridden in neoplastic thyrocytes by NF-kappaB activation.

PubMed

Bravo, Susana B; Pampín, Sandra; Cameselle-Teijeiro, José; Carneiro, Carmen; Domínguez, Fernando; Barreiro, Francisco; Alvarez, Clara V

2003-10-30

Millions of people worldwide suffer goiter, a proliferative disease of the follicular cells of the thyroid that may become neoplastic. Thyroid neoplasms have low proliferative index, low apoptotic index and a high incidence of metastasis. TGF-beta is overexpressed in thyroid follicular tumor cells. To investigate the role of TGF-beta in thyroid tumor progression, we established cultures of human thyrocytes from different proliferative pathologies (Grave's disease, multinodular goiter, follicular adenoma, papillary carcinoma), lymph node metastasis, and a normal thyroid sample. All cultures maintained the thyrocyte phenotype. TGF-beta induced cell-cycle arrest in all cultures, in contrast with results reported for other epithelial tumors. In deprived medium, TGF-beta induced apoptosis in normal thyrocyte cultures and all neoplastic cultures except the metastatic cultures. This apoptosis was mediated by a reduction in p27kip1 levels, inducing cell-cycle initiation. Antisense p27 expression induced apoptosis in the absence of TGF-beta. By contrast, in cells in which p27 was overexpressed, TGF-beta had a survival effect. In growth medium, a net survival effect occurs in neoplastic thyrocytes only, not normal thyrocytes, due to activation of the NF-kappaB survival program. Together, these findings suggest that (a) thyroid neoplasms are due to reduced apoptosis, not increased division, in line with the low proliferative index of these pathologies, and (b) TGF-beta induces apoptosis in normal thyrocytes via p27 reduction, but that in neoplastic thyrocytes this effect is overridden by activation of the NF-kappaB program.

Changes in cerebral glucose metabolism during early abstinence from chronic methamphetamine abuse.

PubMed

Berman, S M; Voytek, B; Mandelkern, M A; Hassid, B D; Isaacson, A; Monterosso, J; Miotto, K; Ling, W; London, E D

2008-09-01

Changes in brain function during the initial weeks of abstinence from chronic methamphetamine abuse may substantially affect clinical outcome, but are not well understood. We used positron emission tomography with [F-18]fluorodeoxyglucose (FDG) to quantify regional cerebral glucose metabolism, an index of brain function, during performance of a vigilance task. A total of 10 methamphetamine-dependent subjects were tested after 5-9 days of abstinence, and after 4 additional weeks of supervised abstinence. A total of 12 healthy control subjects were tested at corresponding times. Global glucose metabolism increased between tests (P=0.01), more in methamphetamine-dependent (10.9%, P=0.02) than control subjects (1.9%, NS). Glucose metabolism did not change in subcortical regions of methamphetamine-dependent subjects, but increased in neocortex, with maximal increase (>20%) in parietal regions. Changes in reaction time and self-reports of negative affect varied more in methamphetamine-dependent than in control subjects, and correlated both with the increase in parietal glucose metabolism, and decrease in relative activity (after scaling to the global mean) in some regions. A robust relationship between change in self-reports of depressive symptoms and relative activity in the ventral striatum may have great relevance to treatment success because of the role of this region in drug abuse-related behaviors. Shifts in cortical-subcortical metabolic balance either reflect new processes that occur during early abstinence, or the unmasking of effects of chronic methamphetamine abuse that are obscured by suppression of cortical glucose metabolism that continues for at least 5-9 days after cessation of methamphetamine self-administration.

Determination of minimal clinically important change in early and advanced Parkinson's disease.

PubMed

Hauser, Robert A; Auinger, Peggy

2011-04-01

Two common primary efficacy outcome measures in Parkinson's disease (PD) are change in Unified Parkinson's Disease Rating Scale (UPDRS) scores in early PD and change in "off" time in patients with motor fluctuations. Defining the minimal clinically important change (MCIC) in these outcome measures is important to interpret the clinical relevance of changes observed in clinical trials and other situations. We analyzed data from 2 multicenter, placebo-controlled, randomized clinical trials of rasagiline; TEMPO studied 404 early PD subjects, and PRESTO studied 472 levodopa-treated subjects with motor fluctuations. An anchor-based approach using clinical global impression of improvement (CGI-I) was used to determine MCIC for UPDRS scores and daily "off" time. MCIC was defined as mean change in actively treated subjects rated minimally improved on CGI-I. Receiver operating characteristic (ROC) curves defined optimal cutoffs discriminating between changed and unchanged subjects. MCIC for improvement in total UPDRS score (parts I-III) in early PD was determined to be -3.5 points based on mean scores and -3.0 points based on ROC curves. In addition, we found an MCIC for reduction in "off" time of 1.0 hours as defined by mean reduction in "off" time in active treated subjects self-rated as minimally improved on CGI-I minus mean reduction in "off" time in placebo-treated subjects self-rated as unchanged (1.9-0.9 hours). We hypothesize that many methodological factors can influence determination of the MCIC, and a range of values is likely to emerge from multiple studies. Copyright © 2011 Movement Disorder Society.

Transient early food restriction leads to hypothalamic changes in the long-lived crowded litter female mice.

PubMed

Sadagurski, Marianna; Landeryou, Taylor; Cady, Gillian; Bartke, Andrzej; Bernal-Mizrachi, Ernesto; Miller, Richard A

2015-04-01

Transient nutrient restriction in the 3 weeks between birth and weaning (producing "crowded litter" or CL mice) leads to a significant increase in lifespan and is associated with permanent changes in energy homeostasis, leptin, and insulin sensitivity. Here, we show this brief period of early food restriction leads to permanent modulation of the arcuate nucleus of the hypothalamus (ARH), markedly increasing formation of both orexigenic agouti-related peptide (AgRP) and anorexigenic proopiomelanocortin (POMC) projections to the paraventricular nucleus of the hypothalamus (PVH). An additional 4 weeks of caloric restriction, after weaning, does not further intensify the formation of AgRP and POMC projections. Acute leptin stimulation of 12-month-old mice leads to a stronger increase in the levels of hypothalamic pStat3 and cFos activity in CL mice than in controls, suggesting that preweaning food restriction leads to long-lasting enhancement of leptin signaling. In contrast, FoxO1 nuclear exclusion in response to insulin is equivalent in young adult CL and control mice, suggesting that hypothalamic insulin signaling is not modulated by the crowded litter intervention. Markers of hypothalamic reactive gliosis associated with aging, such as Iba1-positive microglia and GFAP-positive astrocytes, are significantly reduced in CL mice as compared to controls at 12 and 22 months of age. Lastly, age-associated overproduction of TNF-α in microglial cells is reduced in CL mice than in age-matched controls. Together, these results suggest that transient early life nutrient deprivation leads to long-term hypothalamic changes which may contribute to the longevity of CL mice. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Osteoclast-targeting small molecules for the treatment of neoplastic bone metastases.

PubMed

Kawatani, Makoto; Osada, Hiroyuki

2009-11-01

Osteoclasts are highly specialized cells that resorb bone, and their abnormal activity is implicated in a variety of human bone diseases. In neoplastic bone metastasis, the bone destruction caused by osteoclasts is not only associated with the formation and progression of metastatic lesions, but also could contribute to frequent complications such as severe pain and pathological fractures, which greatly diminish the quality of life of patients. Bisphosphonates, potent antiresorptive drugs, have been shown to have efficacy for treating bone metastases in many types of cancer, and the development of various molecularly targeted agents is currently proceeding. Thus, inhibition of osteoclast function is now established as an important treatment strategy for bony metastases. This review focuses on promising small molecules that disrupt osteoclast function and introduces our chemical/biological approach for identifying osteoclast-targeting small molecular inhibitors.

Immunoelectron microscopic localisation of keratin and luminal epithelial antigens in normal and neoplastic urothelium.

PubMed

Wilson, P D; Nathrath, W B; Trejdosiewicz, L K

1982-01-01

Immunoelectron microscope cytochemistry was carried out on 2% paraformaldehyde fixed, 50 mu sections of normal urothelium and bladder carcinoma cells in culture using antisera raised in rabbits to human 40-63 000 MW epidermal "broad spectrum" keratin and calf urothelial "luminal epithelial antigen" (aLEA) Both the unconjugated and indirect immunoperoxidase-DAB techniques were used before routine embedding. The localisation of both keratin and luminal epithelial antigen (LEA) was similar in normal and neoplastic cells and reaction product was associated not only with tonofilaments but also lining membrane vesicles and on fine filaments in the cytoplasmic ground substance.

Climate change implications and use of early warning systems for global dust storms

USGS Publications Warehouse

Harriman, Lindsey M.

2014-01-01

With increased changes in land cover and global climate, early detection and warning of dust storms in conjunction with effective and widespread information broadcasts will be essential to the prevention and mitigation of future risks and impacts. Human activities, seasonal variations and long-term climatic patterns influence dust storms. More research is needed to analyse these factors of dust mobilisation to create more certainty for the fate of vulnerable populations and ecosystems in the future. Early warning and communication systems, when in place and effectively implemented, can offer some relief to these vulnerable areas. As an issue that affects many regions of the world, there is a profound need to understand the potential changes and ultimately create better early warning systems for dust storms.

Does the Brief Observation of Social Communication Change Help Moving Forward in Measuring Change in Early Autism Intervention Studies?

ERIC Educational Resources Information Center

Pijl, Mirjam K. J.; Rommelse, Nanda N. J.; Hendriks, Monica; De Korte, Manon W. P.; Buitelaar, Jan K.; Oosterling, Iris J.

2018-01-01

The field of early autism research is in dire need of outcome measures that adequately reflect subtle changes in core autistic behaviors. This article compares the ability of a newly developed measure, the Brief Observation of Social Communication Change (BOSCC), and the Autism Diagnostic Observation Schedule (ADOS) to detect changes in core…

Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes.

PubMed

Xu, Ning; Chua, Angela K; Jiang, Hong; Liu, Ning-Ai; Goodarzi, Mark O

2014-08-01

Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study.

Association between Diverticular Disease and Pre-Neoplastic Colorectal Lesions in an Urban African-American Population.

PubMed

Ashktorab, Hassan; Panchal, Heena; Shokrani, Babak; Paydar, Mansour; Sanderson, Andrew; Lee, Edward L; Begum, Rehana; Haidary, Tahmineh; Laiyemo, Adeyinka O; McDonald-Pinkett, Shelly; Brim, Hassan; Nouraie, Mehdi

2015-01-01

It is unclear whether there is a shared pathway in the development of diverticular disease (DD) and potentially neoplastic colorectal lesions since both diseases are found in similar age groups and populations. To determine the association between DD and colorectal pre-neoplastic lesions in an African-American urban population. Data from 1986 patients who underwent colonoscopy at the Howard University Hospital from January 2012 through December 2012 were analyzed for this study. The presence of diverticula and polyps was recorded using colonoscopy reports. Polyps were further classified into adenoma or hyperplastic polyp based on histopathology reports. Multiple logistic regression was done to analyze the association between DD and colonic lesions. Of the 1986 study subjects, 1,119 (56%) were females, 35% had DD and 56% had at least one polyp. There was a higher prevalence of polyps (70 vs. 49%; OR = 2.3; 95% CI: 1.9-2.8) and adenoma (43 vs. 25%; OR = 2.0; 95% CI: 1.7-2.5) in the diverticular vs. non-diverticula patients. Among patients who underwent screening colonoscopy, the presence of diverticulosis was associated with increased odds of associated polyps (OR = 9.9; 95% CI: 5.4-16.8) and adenoma (OR = 5.1; 95% CI: 3.4-7.8). Patients with DD are more likely to harbor colorectal lesions. These findings call for more vigilance on the part of endoscopists during colonoscopy in patients known to harbor colonic diverticula. © 2015 S. Karger AG, Basel.

Changes in early-successional hardwood forest area in four bird conservation regions across four decades

Treesearch

Sonja N. Oswalt; Kathleen E. Franzreb; David A. Buehler

2012-01-01

Early successional hardwood forests constitute important breeding habitat for many migratory songbirds. Declines in populations of these species suggest changes in habitat availability either on the species’ wintering grounds or on their early successional breeding grounds. We used Forest Inventory and Analysis data from 11 states across four decades to examine changes...

Increased expression of cyclooxygenase-2 protein during rat hepatocarcinogenesis caused by a choline-deficient, L-amino acid-defined diet and chemopreventive efficacy of a specific inhibitor, nimesulide.

PubMed

Denda, Ayumi; Kitayama, Wakashi; Murata, Akiko; Kishida, Hideki; Sasaki, Yasutaka; Kusuoka, Osamu; Tsujiuchi, Toshifumi; Tsutsumi, Masahiro; Nakae, Dai; Takagi, Hidetoshi; Konishi, Yoichi

2002-02-01

Expression of cyclooxygenase (COX)-2 protein during rat hepatocarcinogenesis associated with fatty change, fibrosis, cirrhosis and oxidative DNA damage, caused by a choline-deficient, L-amino acid-defined (CDAA) diet were investigated in F344 male rats, along with the chemopreventive efficacy of the specific COX-2 inhibitor, nimesulide (NIM). Nimesulide, which was administered in the diet at concentrations of 200, 400, 600 and 800 p.p.m. for 12 weeks, decreased the number and size of preneoplastic enzyme-altered liver foci, levels of oxidative DNA damage, and the grade and incidence of fibrosis in a dose-dependent manner. A preliminary long-term study of 65 weeks also revealed that 800 p.p.m. NIM decreased the multiplicity of neoplastic nodules and hepatocellular carcinomas and prevented the development of cirrhosis. Western blot analysis revealed that COX-2 protein was barely expressed in control livers and increased approximately 2.9-fold in the livers of rats fed on a CDAA diet for 12 weeks and approximately 4.5-5.4-fold in tumors, with a diameter larger than 5 mm, at 80 weeks. Immunohistochemically, COX-2 protein was positive in sinusoidal and stromal cells in fibrotic septa, which were identified by immunoelectron microscopy as Kupffer cells, macrophages, either activated Ito cells or fibroblasts, after exposure to the CDAA diet for 12 weeks, whereas it was only occasionally weakly positive in sinusoidal, probably Kupffer, cells in control livers. In neoplastic nodules in rats fed on a CDAA diet for 30 and 80 weeks, sinusoidal cells and cells with relatively large round nuclei and scanty cytoplasm were strongly positive for COX-2 protein, with the neoplastic hepatocytes in the minority of the nodules, but not the cancer cells, being moderately positive. These results clearly indicate that rat hepatocarcinogenesis, along with fatty change, fibrosis and cirrhosis, is associated with increased expression of COX-2 protein, and point to the chemopreventive efficacy

Response of Late Carboniferous and Early Permian Plant Communities to Climate Change

NASA Astrophysics Data System (ADS)

Dimichele, William A.; Pfefferkorn, Hermann W.; Gastaldo, Robert A.

Late Carboniferous and Early Permian strata record the transition from a cold interval in Earth history, characterized by the repeated periods of glaciation and deglaciation of the southern pole, to a warm-climate interval. Consequently, this time period is the best available analogue to the Recent in which to study patterns of vegetational response, both to glacial-interglacial oscillation and to the appearance of warm climate. Carboniferous wetland ecosystems were dominated by spore-producing plants and early gymnospermous seed plants. Global climate changes, largely drying, forced vegetational changes, resulting in a change to a seed plant-dominated world, beginning first at high latitudes during the Carboniferous, reaching the tropics near the Permo-Carboniferous boundary. For most of this time plant assemblages were very conservative in their composition. Change in the dominant vegetation was generally a rapid process, which suggests that environmental thresholds were crossed, and involved little mixing of elements from the wet and dry floras.

Increased frequency of spontaneous neoplastic transformation in progeny of bystander cells from cultures exposed to densely ionizing radiation.

PubMed

Buonanno, Manuela; de Toledo, Sonia M; Azzam, Edouard I

2011-01-01

An increased risk of carcinogenesis caused by exposure to space radiation during prolonged space travel is a limiting factor for human space exploration. Typically, astronauts are exposed to low fluences of ionizing particles that target only a few cells in a tissue at any one time. The propagation of stressful effects from irradiated to neighboring bystander cells and their transmission to progeny cells would be of importance in estimates of the health risks of exposure to space radiation. With relevance to the risk of carcinogenesis, we investigated, in model C3H 10T½ mouse embryo fibroblasts (MEFs), modulation of the spontaneous frequency of neoplastic transformation in the progeny of bystander MEFs that had been in co-culture 10 population doublings earlier with MEFs exposed to moderate doses of densely ionizing iron ions (1 GeV/nucleon) or sparsely ionizing protons (1 GeV). An increase (P<0.05) in neoplastic transformation frequency, likely mediated by intercellular communication through gap junctions, was observed in the progeny of bystander cells that had been in co-culture with cells irradiated with iron ions, but not with protons.

Assessment of the "fish tumors or other deformities" beneficial use impairment in brown bullhead (Ameiurus nebulosus): II. Liver neoplasia

USGS Publications Warehouse

Blazer, V.S.; Rafferty, S.D.; Baumman, P.C.; Smith, S.B.; Obert, E.C.

2009-01-01

Liver pathology of fishes, including neoplastic and preneoplastic lesions, is widely used as an indicator of exposure to anthropogenic contaminants. By definition, the "fish tumor or other deformities" beneficial use impairment (BUI) at Great Lakes Areas of Concern (AOC) includes neoplastic and preneoplastic liver lesions in brown bullhead (Ameiurus nebulosus) or suckers. Unfortunately, adequate guidelines for defining neoplastic and preneoplastic liver lesions or determining rates at unimpacted control sites were not provided and different criteria have been used. In some cases, only neoplastic changes were used to calculate tumor prevalence, in some both neoplastic and preneoplastic changes and in some it is difficult to determine which changes were included. Using standardized criteria, the prevalence of liver neoplasia was compared at eight AOC during 1998-2000. The Cuyahoga River had the highest prevalence (25.0%), while the Maumee River had the lowest (3.9%). The Buffalo (4.8%), Detroit (5.9%), Ashtabula (6.8%), Niagara (7.5%) and Black (8.9%) rivers were intermediate, as was Presque Isle Bay (7.1%). From 2002 to 2007 the prevalence of liver neoplasia at Presque Isle Bay ranged from a low of 2.1% (2002) to a high of 12.0% (2007). Non-AOC sites, as potential reference sites, also were monitored during this time. By combining years and sites, the prevalence of liver neoplasia in bullhead (aged 2 to 12 years) at inland lakes was 0.7%, at bays/harbors was 1.6% and at tributary sites was 4.1%. This is the same trend (inland lakes < bays/harbors < tributaries < Presque Isle Bay) noted for orocutaneous neoplasms.

Comparison of the circadian variation in cell proliferation in normal and neoplastic colonic epithelial cells.

PubMed

Kennedy, M F; Tutton, P J; Barkla, D H

1985-09-15

Circadian variations in cell proliferation in normal tissues have been recognised for many years but comparable phenomena in neoplastic tissues appear not to have been reported. Adenomas and carcinomas were induced in mouse colon by injection of dimethylhydrazine (DMH) and cell proliferation in these tumors was measured stathmokinetically. In normal intestine cell proliferation is fastest at night whereas in both adenomas and carcinomas it was found to be slower at night than in the middle of the day. Chemical sympathectomy was found to abolish the circadian variation in tumor cell proliferation.

Differential diagnosis of a neoplastic condition in a prehistoric juvenile individual from La Falda site, Northwest Argentina.

PubMed

Arrieta, Mario A; Mendonça, Osvaldo J; Bordach, María A

2018-06-01

Bone neoplasms or tumors are of great interest for paleopathological studies due to their close relationship with health and survivorship as well as for their epidemiologic and demographic relevance. However, the identification of these lesions in archaeological specimens is very uncommon. The aim of this paper is to report the case of skeleton R5 E#1 from the prehistoric cemetery La Falda, in the Northwest region of Argentina. During the osteopathological analysis of the skeletal series, proliferative lesions in several bones of the skeleton of a 7-10-year-old juvenile were observed (i.e., both scapulae; left clavicle, humerus, and ulna, both os coxae, femora, and fibulae, and right foot bones). Age-at-death estimation, location and distribution pattern, and morphological appearances of the lesions indicated that this juvenile suffered from a neoplastic condition. A comprehensive differential diagnosis was carried out, suggesting that these lesions were compatible with hereditary multiple osteochondromas. However, Ewing's sarcoma was not definitively ruled out as a probable diagnosis. Thus, this work adds new evidence to the existence of neoplastic conditions in the prehistoric populations of the Americas, and it contributes original data to perform a differential diagnosis for multiple proliferative lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Specific early fine structural changes in the lung following irradiation. [X rays; mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penney, D.P.; Rubin, P.

1977-01-01

The lungs of mice were irradiated with single and fractionated doses of 1000 R, 2000 R, and 3000 R and recovered 1 hr, 1 day, 1 week, and 1 month following exposure. Electron microscopy revealed early changes in the decrement of lamellar bodies of Type II pneumocytes and increased fibrous content and edema in the septal walls of all animals treated. Those lungs treated with fractionated doses of irradiation displayed more pronounced cellular damage than did singly-dosed lungs. It is proposed that these early changes may predict for subsequent atelectasis.

Global situational awareness and early warning of high-consequence climate change.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Backus, George A.; Carr, Martin J.; Boslough, Mark Bruce Elrick

2009-08-01

Global monitoring systems that have high spatial and temporal resolution, with long observational baselines, are needed to provide situational awareness of the Earth's climate system. Continuous monitoring is required for early warning of high-consequence climate change and to help anticipate and minimize the threat. Global climate has changed abruptly in the past and will almost certainly do so again, even in the absence of anthropogenic interference. It is possible that the Earth's climate could change dramatically and suddenly within a few years. An unexpected loss of climate stability would be equivalent to the failure of an engineered system on amore » grand scale, and would affect billions of people by causing agricultural, economic, and environmental collapses that would cascade throughout the world. The probability of such an abrupt change happening in the near future may be small, but it is nonzero. Because the consequences would be catastrophic, we argue that the problem should be treated with science-informed engineering conservatism, which focuses on various ways a system can fail and emphasizes inspection and early detection. Such an approach will require high-fidelity continuous global monitoring, informed by scientific modeling.« less

Development of a widefield reflectance and fluorescence imaging device for the detection of skin and oral cancer

NASA Astrophysics Data System (ADS)

Pratavieira, S.; Santos, P. L. A.; Bagnato, V. S.; Kurachi, C.

2009-06-01

Oral and skin cancers constitute a major global health problem that cause great impact in patients. The most common screening method for oral cancer is visual inspection and palpation of the mouth. Visual examination relies heavily on the experience and skills of the physician to identify and delineate early premalignant and cancer changes, which is not simple due to the similar characteristics of early stage cancers and benign lesions. Optical imaging has the potential to address these clinical challenges. Contrast between normal and neoplastic areas may be increased, distinct to the conventional white light, when using illumination and detection conditions. Reflectance imaging can detect local changes in tissue scattering and absorption and fluorescence imaging can probe changes in the biochemical composition. These changes have shown to be indicatives of malignant progression. Widefield optical imaging systems are interesting because they may enhance the screening ability in large regions allowing the discrimination and the delineation of neoplastic and potentially of occult lesions. Digital image processing allows the combination of autofluorescence and reflectance images in order to objectively identify and delineate the peripheral extent of neoplastic lesions in the skin and oral cavity. Combining information from different imaging modalities has the potential of increasing diagnostic performance, due to distinct provided information. A simple widefiled imaging device based on fluorescence and reflectance modes together with a digital image processing was assembled and its performance tested in an animal study.

Sweet-spot training for early esophageal cancer detection

NASA Astrophysics Data System (ADS)

van der Sommen, Fons; Zinger, Svitlana; Schoon, Erik J.; de With, Peter H. N.

2016-03-01

Over the past decade, the imaging tools for endoscopists have improved drastically. This has enabled physicians to visually inspect the intestinal tissue for early signs of malignant lesions. Besides this, recent studies show the feasibility of supportive image analysis for endoscopists, but the analysis problem is typically approached as a segmentation task where binary ground truth is employed. In this study, we show that the detection of early cancerous tissue in the gastrointestinal tract cannot be approached as a binary segmentation problem and it is crucial and clinically relevant to involve multiple experts for annotating early lesions. By employing the so-called sweet spot for training purposes as a metric, a much better detection performance can be achieved. Furthermore, a multi-expert-based ground truth, i.e. a golden standard, enables an improved validation of the resulting delineations. For this purpose, besides the sweet spot we also propose another novel metric, the Jaccard Golden Standard (JIGS) that can handle multiple ground-truth annotations. Our experiments involving these new metrics and based on the golden standard show that the performance of a detection algorithm of early neoplastic lesions in Barrett's esophagus can be increased significantly, demonstrating a 10 percent point increase in the resulting F1 detection score.

The National Early Childhood Technical Assistance Center Model for Long-Term Systems Change

ERIC Educational Resources Information Center

Kahn, Lynne; Hurth, Joicey; Kasprzak, Christina M.; Diefendorf, Martha J.; Goode, Susan E.; Ringwalt, Sharon S.

2009-01-01

The National Early Childhood Technical Assistance Center was charged by the U.S. Department of Education's Office of Special Education Programs from October 2001 through September 2006 to develop, implement, and evaluate an approach to technical assistance (TA) that would result in sustainable systems change in state early intervention and…

The impact of early symptom change and therapeutic alliance on treatment outcome in cognitive-behavioural therapy for eating disorders.

PubMed

Turner, Hannah; Bryant-Waugh, Rachel; Marshall, Emily

2015-10-01

The present study explored the impact of early symptom change (cognitive and behavioural) and the early therapeutic alliance on treatment outcome in cognitive-behavioural therapy (CBT) for the eating disorders. Participants were 94 adults with diagnosed eating disorders who completed a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment, following the 6th session and at the end of treatment. They also completed a measure of therapeutic alliance following the 6th session. Greater early reduction in dietary restraint and eating concerns, and smaller levels of change in shape concern, significantly predicted later reduction in global eating pathology. The early therapeutic alliance was strong across the three domains of tasks, goals and bond. Early symptom reduction was a stronger predictor of later reduction in eating pathology than early therapeutic alliance. The early therapeutic alliance did not mediate the relationship between early symptom reduction and later reduction in global eating pathology. Instead, greater early symptom reduction predicted a strong early therapeutic alliance. Early clinical change was the strongest predictor of treatment outcome and this also facilitated the development of a strong early alliance. Clinicians should be encouraged to deliver all aspects of evidence-based CBT, including behavioural change. The findings suggest that this will have a positive impact on both the early therapeutic alliance and later change in eating pathology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Roadmap for Early Childhood and K-12 Data Linkages: Key Focus Areas to Ensure Quality Implementation. Quality Implementation Roadmaps

ERIC Educational Resources Information Center

Data Quality Campaign, 2016

2016-01-01

Every state can create secure, robust linkages between early childhood and K-12 data systems, and effectively use the information from these linkages to implement initiatives to support programs and children, answer key policy questions, and be transparent about how the state's early childhood investments prepare students for success in school and…

Mountains as early warning indicators of climate change

NASA Astrophysics Data System (ADS)

Williams, M. W.

2015-12-01

The panoramic splendor and complexity of mountain environments have inspired and challenged humans for centuries. These areas have been variously perceived as physical structures to be conquered, as sites of spiritual inspiration, and as some of the last untamed natural places on Earth. In our time, the perception that "mountains are forever" may provide solace to those seeking stability in a rapidly changing world. However, changes in the hydrology and in the abundance and species composition of the native flora and fauna of mountain ecosystems are potential bellwethers of global change, because these systems have a propensity to amplify environmental changes within specific portions of this landscape. Mountain areas are thus sentinels of climate change. We are seeing effects today in case histories I present from the Himalaya's, Andes, Alps, and Rocky Mountains. Furthermore, these ecosystem changes are occurring in mountain areas before they occur in downstream ecosystems. Thus, mountains are early warning indicators of perturbations such as climate change. The sensitivity of mountain ecosystems begs for enhanced protection and worldwide protection. Our understanding of the processes that control mountain ecosystems—climate interactions, snowmelt runoff, biotic diversity, nutrient cycling—is much less developed compared to downstream ecosystems where human habitation and development has resulted in large investments in scientific knowledge to sustain health and agriculture. To address these deficiencies, I propose the formation of an international mountain research consortium.

Tofacitinib in Rheumatoid Arthritis: Lack of Early Change in Disease Activity Predicts a Low Probability of Achieving Low Disease Activity at Month 6.

PubMed

Van Vollenhoven, Ronald F; Lee, Eun Bong; Fallon, Lara; Zwillich, Samuel H; Wilkinson, Bethanie; Chapman, Douglass; Demasi, Ryan; Keystone, Edward

2018-04-26

Optimal targeted treatment in rheumatoid arthritis requires early identification of failure to respond. This post-hoc analysis explored the relationship between early disease activity changes and achievement of low disease activity (LDA) and remission targets with tofacitinib. Data were from two randomized, double-blind, Phase 3 studies. In ORAL Start (NCT01039688), methotrexate (MTX)-naïve patients received tofacitinib 5 or 10 mg BID, or MTX, for 24 months. In placebo-controlled ORAL Standard (NCT00853385), MTX-inadequate responder (MTX-IR) patients received tofacitinib 5 or 10 mg BID or adalimumab 40 mg Q2W, with MTX, for 12 months. Probabilities of achieving LDA (CDAI ≤10; DAS28-4[ESR] ≤3.2) at months 6 and 12 were calculated, given failure to achieve threshold improvement from baseline (change in CDAI ≥6; DAS28-4[ESR] ≥1.2) at month 1 or 3. In ORAL Start, 7.2% and 5.4% of patients receiving tofacitinib 5 and 10 mg BID, respectively, failed to improve CDAI ≥6 at month 3; of those who failed, 3.8% and 28.6%, respectively, achieved month 6 CDAI-defined LDA. In ORAL Standard, 18.8% and 17.5% of patients receiving tofacitinib 5 and 10 mg BID, respectively, failed to improve CDAI ≥6 at month 3; of those who failed, 0% and 2.9%, respectively, achieved month 6 CDAI-defined LDA. Findings were similar when considering month 1 improvements or DAS28-4(ESR) thresholds. In MTX-IR patients, lack of response to tofacitinib after 1 or 3 months predicted low probability of achieving LDA at month 6. Lack of early response may be considered when deciding whether to continue treatment with tofacitinib. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Early Changes in Atrial Electromechanical Coupling in Patients with Hypertension: Assessment by Tissue Doppler Imaging.

PubMed

Avci, Burcak Kilickiran; Gulmez, Oyku; Donmez, Guclu; Pehlivanoglu, Seckin

2016-06-05

Hypertension (HT) is associated with atrial electrophysiological abnormalities. Echocardiographic pulsed wave tissue Doppler imaging (TDI) is one of the noninvasive methods for evaluation of atrial electromechanical properties. The aims of our study were to investigate the early changes in atrial electromechanical conduction in patients with HT and to assess the parameters that affect atrial electromechanical conduction. Seventy-six patients with HT (41 males, mean age 52.6 ± 9.0 years) and 41 controls (22 males, mean age 49.8 ± 7.9 years) were included in the study. Atrial electromechanical coupling at the right (PRA), left (PLA), interatrial septum (PIS) were measured with TDI. Intra- (right: PIS-PRA, left: PLA-PIS) and inter-atrial (PLA-PRA) electromechanical delays were calculated. Maximum P-wave duration (Pmax) was calculated from 12-lead electrocardiogram. Atrial electromechanical coupling at PLA (76.6 ± 14.1 ms vs. 82.9 ± 15.8 ms, P = 0.036), left intra-atrial (10.9 ± 5.0 ms vs. 14.0 ± 9.7 ms, P = 0.023), right intra-atrial (10.6 ± 7.8 ms vs. 14.5 ± 10.1 ms, P = 0.035), and interatrial electromechanical (21.4 ± 9.8 ms vs. 28.3 ± 12.7 ms, P = 0.003) delays were significantly longer in patients with HT. The linear regression analysis showed that left ventricular (LV) mass index and Pmax were significantly associated with PLA (P = 0.001 and P = 0.002, respectively), and the LV mass index was the only related factor for interatrial delay (P = 0.001). Intra- and interatrial electromechanical delay, PLA were significantly prolonged in hypertensive patients. LV mass index and Pmax were significantly associated with PLA, and the LV mass index was the only related factor for interatrial delay. The atrial TDI can be a valuable method to assess the early changes of atrial electromechanical conduction properties in those patients.

Early Changes in Atrial Electromechanical Coupling in Patients with Hypertension: Assessment by Tissue Doppler Imaging

PubMed Central

Avci, Burcak Kilickiran; Gulmez, Oyku; Donmez, Guclu; Pehlivanoglu, Seckin

2016-01-01

Background: Hypertension (HT) is associated with atrial electrophysiological abnormalities. Echocardiographic pulsed wave tissue Doppler imaging (TDI) is one of the noninvasive methods for evaluation of atrial electromechanical properties. The aims of our study were to investigate the early changes in atrial electromechanical conduction in patients with HT and to assess the parameters that affect atrial electromechanical conduction. Methods: Seventy-six patients with HT (41 males, mean age 52.6 ± 9.0 years) and 41 controls (22 males, mean age 49.8 ± 7.9 years) were included in the study. Atrial electromechanical coupling at the right (PRA), left (PLA), interatrial septum (PIS) were measured with TDI. Intra- (right: PIS-PRA, left: PLA-PIS) and inter-atrial (PLA-PRA) electromechanical delays were calculated. Maximum P-wave duration (Pmax) was calculated from 12-lead electrocardiogram. Results: Atrial electromechanical coupling at PLA (76.6 ± 14.1 ms vs. 82.9 ± 15.8 ms, P = 0.036), left intra-atrial (10.9 ± 5.0 ms vs. 14.0 ± 9.7 ms, P = 0.023), right intra-atrial (10.6 ± 7.8 ms vs. 14.5 ± 10.1 ms, P = 0.035), and interatrial electromechanical (21.4 ± 9.8 ms vs. 28.3 ± 12.7 ms, P = 0.003) delays were significantly longer in patients with HT. The linear regression analysis showed that left ventricular (LV) mass index and Pmax were significantly associated with PLA (P = 0.001 and P = 0.002, respectively), and the LV mass index was the only related factor for interatrial delay (P = 0.001). Conclusions: Intra- and interatrial electromechanical delay, PLA were significantly prolonged in hypertensive patients. LV mass index and Pmax were significantly associated with PLA, and the LV mass index was the only related factor for interatrial delay. The atrial TDI can be a valuable method to assess the early changes of atrial electromechanical conduction properties in those patients. PMID:27231168

Early Embryonic Androgen Exposure Induces Transgenerational Epigenetic and Metabolic Changes

PubMed Central

Xu, Ning; Chua, Angela K.; Jiang, Hong; Liu, Ning-Ai

2014-01-01

Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study. PMID:24992182

12 CFR 5.50 - Change in bank control; reporting of stock loans.

Code of Federal Regulations, 2012 CFR

2012-01-01

... are financial in nature (as defined in section 4(k) of the Bank Holding Company Act of 1956 (12 U.S.C... 12 Banks and Banking 1 2012-01-01 2012-01-01 false Change in bank control; reporting of stock... in bank control; reporting of stock loans. (a) Authority. 12 U.S.C. 93a, 1817(j), and 12 U.S.C...

12 CFR 5.50 - Change in bank control; reporting of stock loans.

Code of Federal Regulations, 2013 CFR

2013-01-01

... are financial in nature (as defined in section 4(k) of the Bank Holding Company Act of 1956 (12 U.S.C... 12 Banks and Banking 1 2013-01-01 2013-01-01 false Change in bank control; reporting of stock... in bank control; reporting of stock loans. (a) Authority. 12 U.S.C. 93a, 1817(j), and 12 U.S.C...

Upper limb module in non-ambulant patients with spinal muscular atrophy: 12 month changes.

PubMed

Sivo, Serena; Mazzone, Elena; Antonaci, Laura; De Sanctis, Roberto; Fanelli, Lavinia; Palermo, Concetta; Montes, Jacqueline; Pane, Marika; Mercuri, Eugenio

2015-03-01

Recent studies have suggested that in non-ambulant patients affected by spinal muscular atrophy the Upper Limb Module can increase the range of activities assessed by the Hammersmith Functional Motor Scale Expanded. The aim of this study was to establish 12-month changes in the Upper Limb Module in a cohort of non-ambulant spinal muscular atrophy patients and their correlation with changes on the Hammersmith Functional Motor Scale Expanded. The Upper Limb Module scores ranged between 0 and 17 (mean 10.23, SD 4.81) at baseline and between 1 and 17 at 12 months (mean 10.27, SD 4.74). The Hammersmith Functional Motor Scale Expanded scores ranged between 0 and 34 (mean 12.43, SD 9.13) at baseline and between 0 and 34 at 12 months (mean 12.08, SD 9.21). The correlation betweeen the two scales was 0.65 at baseline and 0.72 on the 12 month changes. Our results confirm that the Upper Limb Module can capture functional changes in non-ambulant spinal muscular atrophy patients not otherwise captured by the other scale and that the combination of the two measures allows to capture changes in different subgroups of patients in whom baseline scores and functional changes may be influenced by several variables such as age. Copyright © 2014 Elsevier B.V. All rights reserved.

Early sensory encoding of affective prosody: neuromagnetic tomography of emotional category changes.

PubMed

Thönnessen, Heike; Boers, Frank; Dammers, Jürgen; Chen, Yu-Han; Norra, Christine; Mathiak, Klaus

2010-03-01

In verbal communication, prosodic codes may be phylogenetically older than lexical ones. Little is known, however, about early, automatic encoding of emotional prosody. This study investigated the neuromagnetic analogue of mismatch negativity (MMN) as an index of early stimulus processing of emotional prosody using whole-head magnetoencephalography (MEG). We applied two different paradigms to study MMN; in addition to the traditional oddball paradigm, the so-called optimum design was adapted to emotion detection. In a sequence of randomly changing disyllabic pseudo-words produced by one male speaker in neutral intonation, a traditional oddball design with emotional deviants (10% happy and angry each) and an optimum design with emotional (17% happy and sad each) and nonemotional gender deviants (17% female) elicited the mismatch responses. The emotional category changes demonstrated early responses (<200 ms) at both auditory cortices with larger amplitudes at the right hemisphere. Responses to the nonemotional change from male to female voices emerged later ( approximately 300 ms). Source analysis pointed at bilateral auditory cortex sources without robust contribution from other such as frontal sources. Conceivably, both auditory cortices encode categorical representations of emotional prosodic. Processing of cognitive feature extraction and automatic emotion appraisal may overlap at this level enabling rapid attentional shifts to important social cues. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Sex differences in depression-like behavior after nerve injury are associated with differential changes in brain-derived neurotrophic factor levels in mice subjected to early life stress.

PubMed

Nishinaka, Takashi; Kinoshita, Megumi; Nakamoto, Kazuo; Tokuyama, Shogo

2015-04-10

We recently demonstrated that exposure to early life stress exacerbates nerve injury-induced thermal and mechanical hypersensitivity in adult male and female mice. Accumulating evidence suggests that chronic pain causes emotional dysfunction, such as anxiety and depression. In the present study, we investigated the impact of early life stress on depression-like behavior after nerve injury in mice. In addition, we examined the expression of brain-derived neurotrophic factor (BDNF), which is known to be involved in the pathogenesis of depression. Early life stress was induced by maternal separation between 2 and 3 weeks of age combined with social isolation after weaning (MSSI). At 9 weeks of age, the sciatic nerve was partially ligated to elicit neuropathic pain. Depression-like behavior was evaluated using the forced swim test at 12 weeks of age. Tissue samples from different regions of the brain were collected at the end of maternal separation (3 weeks of age) or after the forced swim test (12 weeks of age). At 12 weeks of age, immobility time in the forced swim test was increased only in MSSI-stressed female mice with nerve injury. BDNF expression was increased in male, but not female, MSSI-stressed mice at 3 weeks of age. However, MSSI stress did not impact BDNF expression in male or female mice at 12 weeks of age. Our findings suggest that exposure to early life stress exacerbates emotional dysfunction induced by neuropathic pain in a sex-dependent manner. Changes in BDNF expression after early life stress may be associated with neuropathic pain-induced depression-like behavior in adulthood. Furthermore, sex differences in BDNF expression after exposure to early life stress may contribute to sex-specific susceptibility to neuropathic pain-induced emotional dysfunction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Neoplastic transformation of SV40-immortalized human urinary tract epithelial cells by in vitro exposure to 3-methylcholanthrene.

PubMed

Reznikoff, C A; Loretz, L J; Christian, B J; Wu, S Q; Meisner, L F

1988-08-01

Normal human urinary tract epithelial cells (HUC) were neoplastically transformed in vitro using a step-wise strategy. First, a partially transformed non-virus-producing cell line was obtained after infection of HUC with simian virus 40 (SV40). This cell line (SV-HUC-1) was demonstrated to be clonal in origin, as 100% of cells contained at least five of seven marker chromosomes. Marker chromosomes were formed by balanced translocations resulting in a 'pseudodiploid' cell line. SV-HUC-1 showed altered growth properties in vitro (e.g. anchorage independent growth) but failed to form tumors in athymic nude mice, even after 3 years in culture (80 passages). In the studies reported here, SV-HUC-1 at early passages (P15-P19) were exposed to 3-methylcholanthrene (MCA) in three separate experiments. After a six-week post-treatment period of cell culture, cells were inoculated s.c. into athymic nude mice. In all experiments, MCA-treated SV-HUC-1 formed carcinomas in mice usually with a latent period of 5-8 weeks. These carcinomas showed heterogeneity with respect to histopathologies and growth properties in the mice and karyotypes. All the tumors retained SV-HUC-1 chromosome markers, but each independent transformant was aneuploid and contained unique new marker chromosomes. Chromosomes usually altered in tumor cells included numbers 3, 5, 6, 9, 11 and 13. Mutations in the ras family of cellular proto-oncogenes resulting in altered mobility of the p21 protein product were not detected in six cell lines established from independently derived tumors. It is not yet known whether other cellular proto-oncogenes are activated in these tumorigenic transformants. Neither control SV-HUC-1 (which were not exposed to MCA), nor early passage HUC exposed to MCA formed tumors when inoculated into mice. Thus, the tumorigenic transformation of HUC resulted from the combined actions of SV40 and MCA.

Drought early warning and risk management in a changing environment

NASA Astrophysics Data System (ADS)

Pulwarty, R. S.

2011-12-01

Drought has long been recognized as falling into the category of incremental but long-term and cumulative environmental changes, also termed slow-onset or creeping events. These event types would include: air and water quality decline, desertification processes, deforestation and forest fragmentation, loss of biodiversity and habitats, and nitrogen overloading, among others. Climate scientists continue to struggle with recognizing the onset of drought and scientists and policy makers continue to debate the basis (i.e., criteria) for declaring an end to a drought. Risk-based management approaches to drought planning at the national and regional levels have been recommended repeatedly over the years but their prototyping, testing and operational implementation have been limited. This presentation will outline two avenues for disaster risk reduction in the context of drought (1) integrated early warning information systems, and (2) linking disaster risk reduction to climate change adaptation strategies. Adaptation involves not only using operational facilities and infrastructure to cope with the immediate problems but also leaving slack or reserve for coping with multiple stress problems that produce extreme impacts and surprise. Increasing the 'anticipatability' of an event, involves both monitoring of key indicators from appropriate baseline data, and observing early warning signs that assumptions in risk management plans are failing and critical transitions are occurring. Illustrative cases will be drawn from the IPCC Special Report on Managing the Risks of Extreme Events and Disasters (2011), the UN Global Assessment of Disaster Risk Reduction (2011) and implementation activities in which the author has been engaged. Most drought early warning systems have tended to focus on the development and use of physical system indicators and forecasts of trends and thresholds. We show that successful early warning systems that meet expectations of risk management also have

Diffusion and Binding of Mismatch Repair Protein, MSH2, in Breast Cancer Cells at Different Stages of Neoplastic Transformation

PubMed Central

Sigley, Justin; Jarzen, John; Scarpinato, Karin; Guthold, Martin; Pu, Tracey; Nelli, Daniel; Low, Josiah

2017-01-01

The interior of cells is a highly complex medium, containing numerous organelles, a matrix of different fibers and a viscous, aqueous fluid of proteins and small molecules. The interior of cells is also a highly dynamic medium, in which many components move, either by active transport or passive diffusion. The mobility and localization of proteins inside cells can provide important insights into protein function and also general cellular properties, such as viscosity. Neoplastic transformation affects numerous cellular properties, and our goal was to investigate the diffusional and binding behavior of the important mismatch repair (MMR) protein MSH2 in live human cells at various stages of neoplastic transformation. Toward this end, noncancerous, immortal, tumorigenic, and metastatic mammary epithelial cells were transfected with EGFP and EGFP-tagged MSH2. MSH2 forms two MMR proteins (MutSα and MutSβ) and we assume MSH2 is in the complex MutSα, though our results are similar in either case. Unlike the MutS complexes that bind to nuclear DNA, EGFP diffuses freely. EGFP and MutSα-EGFP diffusion coefficients were determined in the cytoplasm and nucleus of each cell type using fluorescence recovery after photobleaching. Diffusion coefficients were 14–24 μm2/s for EGFP and 3–7 μm2/s for MutSα-EGFP. EGFP diffusion increased in going from noncancerous to immortal cells, indicating a decrease in viscosity, with smaller changes in subsequent stages. MutSα produces an effective diffusion coefficient that, coupled with the free EGFP diffusion measurements, can be used to extract a pure diffusion coefficient and a pseudo-equilibrium constant K*. The MutSα nuclear K* increased sixfold in the first stage of cancer and then decreased in the more advanced stages. The ratio of nuclear to cytoplasmic K*for MutSα increased almost two orders of magnitude in going from noncancerous to immortal cells, suggesting that this quantity may be a sensitive metric for recognizing

Fibroblast growth factor receptor signaling in hereditary and neoplastic disease: biologic and clinical implications.

PubMed

Helsten, Teresa; Schwaederle, Maria; Kurzrock, Razelle

2015-09-01

Fibroblast growth factors (FGFs) and their receptors (FGFRs) are transmembrane growth factor receptors with wide tissue distribution. FGF/FGFR signaling is involved in neoplastic behavior and also development, differentiation, growth, and survival. FGFR germline mutations (activating) can cause skeletal disorders, primarily dwarfism (generally mutations in FGFR3), and craniofacial malformation syndromes (usually mutations in FGFR1 and FGFR2); intriguingly, some of these activating FGFR mutations are also seen in human cancers. FGF/FGFR aberrations reported in cancers are mainly thought to be gain-of-function changes, and several cancers have high frequencies of FGFR alterations, including breast, bladder, or squamous cell carcinomas (lung and head and neck). FGF ligand aberrations (predominantly gene amplifications) are also frequently seen in cancers, in contrast to hereditary syndromes. There are several pharmacologic agents that have been or are being developed for inhibition of FGFR/FGF signaling. These include both highly selective inhibitors as well as multi-kinase inhibitors. Of note, only four agents (ponatinib, pazopanib, regorafenib, and recently lenvatinib) are FDA-approved for use in cancer, although the approval was not based on their activity against FGFR. Perturbations in the FGFR/FGF signaling are present in both inherited and malignant diseases. The development of potent inhibitors targeting FGF/FGFR may provide new tools against disorders caused by FGF/FGFR alterations.

Progressive Pathological Changes in Neurochemical Profile of the Hippocampus and Early Changes in the Olfactory Bulbs of Tau Transgenic Mice (rTg4510).

PubMed

Kim, Jieun; Choi, In-Young; Duff, Karen E; Lee, Phil

2017-06-01

Tauopathies such as Alzheimer's disease and frontotemporal lobe degeneration (FTLD-tau) dementia, characterized by pathologic aggregation of the microtubule-associated tau protein and formation of neurofibrillary tangles, have been linked to neurodegeneration and cognitive decline. The early detection of cerebral abnormalities and the identification of biological contributors to the continuous pathologic processes of neurodegeneration in tauopathies critically hinge on sensitive and reliable measures of biomarkers in the living brain. In this study, we measured alterations in a number of key neurochemicals associated with tauopathy-induced neurodegeneration in the hippocampus and the olfactory bulbs of a transgenic mouse model of FTLD-tauopathy, line rTg4510, using in vivo 1 H magnetic resonance spectroscopy at 9.4 T. The rTg4510 line develops tauopathy at a young age (4-5 months), reaching a severe stage by 8-12 months of age. Longitudinal measurement of neurochemical concentrations in the hippocampus of mice from 5 to 12 months of age showed significant progressive changes with distinctive disease staging patterns including N-acetylaspartate, myo-inositol, γ-aminobutyric acid, glutathione and glutamine. The accompanying hippocampal volume loss measured using magnetic resonance imaging showed significant correlation (p < 0.01) with neurochemical measurements. Neurochemical alterations in the olfactory bulbs were more pronounced than those in the hippocampus in rTg4510 mice. These results demonstrate progressive neuropathology in the mouse model and provide potential biomarkers of early neuropathological events and effective noninvasive monitoring of the disease progression and treatment efficacy, which can be easily translated to clinical studies.

[Aseptic process validation and stability study of an injectable preparation of fructose (5%)-glycerol (10%) as part of a hospital clinical research program on endoscopic curative treatment for early epithelial neoplastic lesions of the gastrointestinal tract].

PubMed

Tall, M L; Salmon, D; Diouf, E; Drai, J; Filali, S; Lépilliez, V; Pioche, M; Laleye, D; Dhelens, C; Ponchon, T; Pivot, C; Pirot, F

2015-03-01

As part of a hospital clinical research program on endoscopic curative treatment for early epithelial neoplastic lesions of the gastrointestinal tract, a new hospital sterile and non-pyrogenic preparation of fructose (5%)-glycerol (10%) was realized. Under pharmaceutical legislation, the provision of this hospital preparation involves of aseptic process validation and achieve a stability study. After the aseptic process validation with Mediafill Test, the preparation was made under aseptic conditions associated with a sterilizing filtration according to the good practices preparation. Prepared flexible bags (100mL of solution) were stored for one year in a climatic chamber (25±2°C). To assess stability, the physicochemical controls (fructose concentration, glycerol concentration, hydroxy-methyl-5 furfural [5-HMF] concentration, sodium concentration, pH measure, osmolality and sub-visible particles count) and microbiological (bioburden, bacterial endotoxin and sterility) were performed at regular intervals for one year. Neither significant decrease of fructose concentration, glycerol concentration and sodium concentration nor pH, 5-HMF, osmolality variations out of specifications were observed for one year. The sub-visible particles count, the bacterial endotoxin and sterility were in accordance with the European pharmacopoeia attesting limpidity, apyrogenicity and sterility of this injectable preparation. The hospital preparation was stable over one year at 25±2°C, ensuring safe administration in humans within the framework of this clinical research. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Anti-Neoplastic Cytotoxicity of Gemcitabine-(C4-amide)-[anti-EGFR] in Dual-combination with Epirubicin-(C3-amide)-[anti-HER2/neu] against Chemotherapeutic-Resistant Mammary Adenocarcinoma (SKBr-3) and the Complementary Effect of Mebendazole

PubMed Central

Coyne, CP; Jones, Toni; Bear, Ryan

2015-01-01

Aims Delineate the feasibility of simultaneous, dual selective “targeted” chemotherapeutic delivery and determine if this molecular strategy can promote higher levels anti-neoplastic cytotoxicity than if only one covalent immunochemotherapeutic is selectively “targeted” for delivery at a single membrane associated receptor over-expressed by chemotherapeutic-resistant mammary adenocarcinoma. Methodology Gemcitabine and epirubicin were covalently bond to anti-EGFR and anti-HER2/neu utilizing a rapid multi-phase synthetic organic chemistry reaction scheme. Determination that 96% or greater gemcitabine or epirubicin content was covalently bond to immunoglobulin fractions following size separation by micro-scale column chromatography was established by methanol precipitation analysis. Residual binding-avidity of gemcitabine-(C4-amide)-[anti-EG-FR] applied in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu] was determined by cell-ELIZA utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) populations. Lack of fragmentation or polymerization was validated by SDS-PAGE/immunodetection/chemiluminescent autoradiography. Anti-neoplastic cytotoxic potency was determined by vitality stain analysis of chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) monolayers known to uniquely over-express EGFR (2 × 105/cell) and HER2/neu (1 × 106/cell) receptor complexes. The covalent immunochemotherapeutics gemcitabine-(C4-amide)-[anti-EGFR] and epirubicin-(C3-amide)-[anti-HER2/neu] were applied simultaneously in dual-combination to determine their capacity to collectively evoke elevated levels of anti-neoplastic cytotoxicity. Lastly, the tubulin/microtubule inhibitor mebendazole evaluated to determine if it’s potential to complemented the anti-neoplastic cytotoxic properties of gemcitabine-(C4-amide)-[anti-EGFR] in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu]. Results Dual-combination of gemcitabine-(C4-amide)-[anti-EGFR] with

Environmental change during the Late Berriasian - Early Valanginian: a prelude to the late Early Valanginian carbon-isotope event?

NASA Astrophysics Data System (ADS)

Morales, Chloé; Schnyder, Johann; Spangenberg, Jorge; Adatte, Thierry; Westermann, Stephane; Föllmi, Karl

2010-05-01

The Valanginian period is well known for a positive excursion in marine and terrestrial δ13C records, which has been interpreted as the consequence of a major perturbation in the global carbon cycle (Lini et al., 1992; Erba et al., 2004). In contrast to the positive δ13C excursions of the Early Aptian and latest Cenomanian, marine organic-rich sediments have only been recognized from a few localities (van de Schootbrugge et al., 2003; Reboulet et al., 2003; Gröcke et al., 2005; Westermann et al., in press). The δ13C excursion began in the late Early Valanginian (campylotoxus ammonite zone) and gradually ended during the Late Valanginian. It is associated with a phase of widespread carbonate-platform drowning on the shelf (Föllmi et al., 1994) and a decline in calcareous nannofossils in the pelagic realm (Erba et al., 2004). As a triggering mechanism, numerous authors invoke the formation of the Parañà-Etendeka flood basalt. The correlation of this episode with the Valanginian δ13C event depends, however, on the absolute ages attributed to the Valanginian stage. The recent geological timescale by Ogg et al. (2008) shows that the major eruptional phase occurred during the Late Valanginian. This may imply that the late Early Valanginian δ13C event resulted from a combination of different factors. Important paleoenvironmental change occurred already in the latest Berriasian and earliest Valanginian, prior to the positive δ13C excursion. An increase in nutrient input near the onset of the δ13C excursion (campylotoxus ammonite zone), which may be considered as a trigger of the carbon cycle perturbation, has been identified in different studies, (Hennig, 2003; Duchamp-Alphonse et al., 2007; Bornemann & Mutterlose, 2008). Heterozoan faunal associations became dominant since the Early Valanginian on the northern Tethyan Helvetic platform and may indicate the beginning of sea-water eutrophication (Föllmi et al., 2007). Clay assemblages in the Tethys and Western

Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

PubMed Central

Berghella, Libera; Ferraro, Elisabetta

2012-01-01

Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257

Epithelial-stromal interface in normal and neoplastic human bladder epithelium.

PubMed

Alroy, J; Gould, V E

1980-01-01

The ultrastructure of the epithelial-stromal interface of the human urinary bladder was studied in biopsy specimens that included 7 normal controls, 1 inverted papilloma, 18 noninvasive papillary carcinomas, and 19 invasive transitional cell carcinomas. In the invasive foci of the transitional cell carcinomas, the underlying basal lamina was attenuated or absent and the number of hemidesmosomes was decreased. These neoplastic cells displayed notably increased numbers of lysosomes, some of which appeared to be in the process of exocytosis. Increased numbers of cytoplasmic filaments adjacent to the plasma membranes at the invading pole of these cells were also observed. Tight junctions and junctional complexes were noticed adjacent to the tumor-stromal interface. None of the aforementioned features was observed in normal transitional epithelium, in inverted papilloma, in noninvasive papillary carcinomas, or in the noninvasive portions of invasive transitional cell carcinomas. Alterations of the epithelial-stromal interface deserve additional studies for they may constitute important parameters in the evaluation of actual or potential invasiveness in the various types of carcinoma of the bladder.

Biogenic amines as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

PubMed

Tutton, P J; Barkla, D H

1987-01-01

The role of extracellular amines such as noradrenaline and serotonin and their interaction with cyclic nucleotides and intracellular polyamines in the regulation of intestinal epithelial cell proliferation is reviewed with particular reference to the differences between normal and neoplastic cells. In respect to the normal epithelium of the small intestine there is a strong case to support the notion that cell proliferation is controlled by, amongst other things, sympathetic nerves. In colonic carcinomas, antagonists for certain serotonin receptors, for histamine H2 receptors and for dopamine D2 receptors inhibit both cell division and tumour growth. Because of the reproducible variations between tumour lines in the response to these antagonists, this inhibition appears to be due to a direct effect on the tumour cells rather than an indirect effect via the tumour host or stroma. This conclusion is supported by the cytocidal effects of toxic congeners of serotonin on the tumour cells. The most salient difference between the amine responses of normal and neoplastic cells relates to the issue of amine uptake. Proliferation of crypt cells is promoted by amine uptake inhibitors, presumably because they block amine re-uptake by the amine secreting cells--sympathetic neurones and enteroendocrine cells. However, tumour cell proliferation is strongly inhibited by amine uptake inhibitors, suggesting that neoplastic cells can, and need to take up the amine before being stimulated by it. Recent revelations in the field of oncogenes also support an important association between amines, cyclic nucleotides and cell division. The ras oncogenes code for a protein that is a member of a family of molecules which relay information from extracellular regulators, such as biogenic amines, to the intracellular regulators, including cyclic nucleotides. Evidence is presented suggesting that enteroendocrine cells, enterocytes, carcinoid tumour cells and adenocarcinoma cells all have the same

Early auditory change detection implicitly facilitated by ignored concurrent visual change during a Braille reading task.

PubMed

Aoyama, Atsushi; Haruyama, Tomohiro; Kuriki, Shinya

2013-09-01

Unconscious monitoring of multimodal stimulus changes enables humans to effectively sense the external environment. Such automatic change detection is thought to be reflected in auditory and visual mismatch negativity (MMN) and mismatch negativity fields (MMFs). These are event-related potentials and magnetic fields, respectively, evoked by deviant stimuli within a sequence of standard stimuli, and both are typically studied during irrelevant visual tasks that cause the stimuli to be ignored. Due to the sensitivity of MMN/MMF to potential effects of explicit attention to vision, however, it is unclear whether multisensory co-occurring changes can purely facilitate early sensory change detection reciprocally across modalities. We adopted a tactile task involving the reading of Braille patterns as a neutral ignore condition, while measuring magnetoencephalographic responses to concurrent audiovisual stimuli that were infrequently deviated either in auditory, visual, or audiovisual dimensions; 1000-Hz standard tones were switched to 1050-Hz deviant tones and/or two-by-two standard check patterns displayed on both sides of visual fields were switched to deviant reversed patterns. The check patterns were set to be faint enough so that the reversals could be easily ignored even during Braille reading. While visual MMFs were virtually undetectable even for visual and audiovisual deviants, significant auditory MMFs were observed for auditory and audiovisual deviants, originating from bilateral supratemporal auditory areas. Notably, auditory MMFs were significantly enhanced for audiovisual deviants from about 100 ms post-stimulus, as compared with the summation responses for auditory and visual deviants or for each of the unisensory deviants recorded in separate sessions. Evidenced by high tactile task performance with unawareness of visual changes, we conclude that Braille reading can successfully suppress explicit attention and that simultaneous multisensory changes can

Otitis Media in Early Childhood and Cognitive, Academic, and Behavior Outcomes at 12 Years of Age.

ERIC Educational Resources Information Center

Roberts, Joanne E.; And Others

1995-01-01

Examined the association between otitis media with effusion (OME) during the first 3 years of life and cognitive, academic performance, and behavior outcomes at 12 years of age. Results indicated that OME during early childhood was not related to intellectual performance, academic achievement, behavior, and attention. Suggests that generalizations…

K-12 Postsecondary Alignment and School Accountability: Investigating High School Responses to California's Early Assessment Program. Research Brief

ERIC Educational Resources Information Center

Kurlaender, Michal; Jackson, Jacob; Howell, Jessica S.

2012-01-01

This brief studies California's introduction of the Early Assessment Program to bridge the gap between K-12 educational standards and postsecondary education requirements, similar to the Common Core State Standards movement.

Early Cerebral Blood Volume Changes Predict Progression After Convection-Enhanced Delivery of Topotecan for Recurrent Malignant Glioma.

PubMed

Surapaneni, Krishna; Kennedy, Benjamin C; Yanagihara, Ted K; DeLaPaz, Robert; Bruce, Jeffrey N

2015-07-01

To assess whether early changes in enhancing tumor volume (eTV) and relative cerebral blood volume (rCBV) 1 month after convection-enhanced delivery of topotecan in patients with recurrent malignant glioma correlated with 6-month disease progression status. Sixteen patients were enrolled in a Phase Ib trial of convection-enhanced delivery of topotecan for recurrent malignant glioma. Each patient was evaluated with serial follow-up magnetic resonance imaging at baseline and at 4- to 8-week intervals. Changes at 1 month compared with baseline in eTV and rCBV were evaluated as potential predictors of 6-month progression status, classified as either progressive disease or nonprogressive disease. Relationships between percent changes in eTV and rCBV at 1 month with the probability of progressive disease at 6 months were estimated by the use of logistic regression analysis. Receiver operating characteristic curves for varying percent change thresholds in eTV and rCBV were evaluated by the use of 6-month progressive disease as the reference. There was a significant difference in the percent change in rCBV at 1 month in patients with progressive disease compared with those with nonprogressive disease at 6 months (+12% vs. -29%, P = 0.02). Logistic regression analysis demonstrated on average that a 10% increase in rCBV at 1 month after convection-enhanced delivery of topotecan was associated with 1.7 times the odds of developing progressive disease at 6 months (95% confidence interval [CI] 1.0-2.9 P = 0.05). Receiver operating characteristic analysis for determining progressive disease at 6 months showed a greater area under the curve with rCBV (0.867; 95% CI 0.66-1.00) than with change in enhancing tumor volume (0.767; 95% CI 0.51-1.00). In this selected population of patients with recurrent malignant glioma treated with convection-enhanced delivery of topotecan, early changes in rCBV at 4 weeks after therapy may help predict progression status at 6 months. Copyright �

Early transcriptional changes in the reef-building coral Acropora aspera in response to thermal and nutrient stress.

PubMed

Rosic, Nedeljka; Kaniewska, Paulina; Chan, Chon-Kit Kenneth; Ling, Edmund Yew Siang; Edwards, David; Dove, Sophie; Hoegh-Guldberg, Ove

2014-12-02

Changes to the environment as a result of human activities can result in a range of impacts on reef building corals that include coral bleaching (reduced concentrations of algal symbionts), decreased coral growth and calcification, and increased incidence of diseases and mortality. Understanding how elevated temperatures and nutrient concentration affect early transcriptional changes in corals and their algal endosymbionts is critically important for evaluating the responses of coral reefs to global changes happening in the environment. Here, we investigated the expression of genes in colonies of the reef-building coral Acropora aspera exposed to short-term sub-lethal levels of thermal (+6°C) and nutrient stress (ammonium-enrichment: 20 μM). The RNA-Seq data provided hundreds of differentially expressed genes (DEGs) corresponding to various stress regimes, with 115 up- and 78 down-regulated genes common to all stress regimes. A list of DEGs included up-regulated coral genes like cytochrome c oxidase and NADH-ubiquinone oxidoreductase and up-regulated photosynthetic genes of algal origin, whereas coral GFP-like fluorescent chromoprotein and sodium/potassium-transporting ATPase showed reduced transcript levels. Taxonomic analyses of the coral holobiont disclosed the dominant presence of transcripts from coral (~70%) and Symbiodinium (~10-12%), as well as ~15-20% of unknown sequences which lacked sequence identity to known genes. Gene ontology analyses revealed enriched pathways, which led to changes in the dynamics of protein networks affecting growth, cellular processes, and energy requirement. In corals with preserved symbiont physiological performance (based on Fv/Fm, photo-pigment and symbiont density), transcriptomic changes and DEGs provided important insight into early stages of the stress response in the coral holobiont. Although there were no signs of coral bleaching after exposure to short-term thermal and nutrient stress conditions, we managed to detect

Neoplastic pleural effusion and intrathoracic metastasis of a scapular osteosarcoma in a dog: a multidisciplinary integrated diagnostic approach.

PubMed

Mesquita, Luis; Mortier, Jeremy; Ressel, Lorenzo; Finotello, Riccardo; Silvestrini, Paolo; Piviani, Martina

2017-06-01

A 10-year-old, female spayed mixed-breed or cross-bred dog was referred to the Small Animal Teaching Hospital of the University of Liverpool due to tachypnea, dyspnea, and pleural effusion not responding to diuretics and antibiotics. The chest was drained and cytology of the pleural fluid was consistent with a modified transudate with presence of atypical cells initially attributed to mesothelial hyperplasia and dysplasia. Computed tomography detected, in addition to the bilateral pleural effusion, diffuse pleural thickening, multiple pleural and pulmonary nodules, and a mineralized and lytic mass in the left scapula. Imaging findings were suggestive of a primary bone tumor with intrathoracic metastasis. Cytology of the left scapular and pleural masses revealed a malignant neoplasm highly suggestive of osteosarcoma. The diagnosis was confirmed by demonstration of a positive cytochemical reaction for alkaline phosphatase on prestained cytology slides. This finding prompted review of the initial interpretation of the pleural effusion cytology. The presence of neoplastic osteoblasts in the thoracic fluid was identified by a combination of cytochemistry, cell pellet immunohistochemistry, and transmission electron microscopy findings. In this report, a multidisciplinary integrated diagnostic approach was used to diagnose and confirm a neoplastic pleural effusion due to osteosarcoma metastasis in a dog. © 2017 American Society for Veterinary Clinical Pathology.

Orientation Discrimination with Macular Changes Associated with Early AMD

PubMed Central

Bedell, Harold E.; Tong, Jianliang; Woo, Stanley Y.; House, Jon R.; Nguyen, Tammy

2010-01-01

Purpose Age-related macular degeneration (AMD) is a condition that progressively reduces central vision in elderly individuals, resulting in a reduced capacity to perform many daily activities and a diminished quality of life. Recent studies identified clinical treatments that can slow or reverse the progression of exudative (wet) AMD and ongoing research is evaluating earlier interventions. Because early diagnosis is critical for an optimal outcome, the goal of this study is to assess psychophysical orientation discrimination for randomly positioned short line segments as a potential indicator of subtle macular changes in eyes with early AMD. Methods Orientation discrimination was measured in a sample of 74 eyes of patients aged 47 to 82 years old, none of which had intermediate or advanced AMD. Amsler-grid testing was performed as well. A masked examiner graded each eye as level 0, 1, 2, or 3 on a streamlined version of the Age-Related Eye Disease Study (AREDS) scale for AMD, based on the presence and extent of macular drusen or retinal pigment epithelium (RPE) changes. Visual acuity in the 74 eyes ranged from 20/15 to 20/40+1, with no significant differences among the grading levels. Humphrey 10–2 and Nidek MP-1 micro-perimetry were used to assess retinal sensitivity at test locations 1° from the locus of fixation. Results Average orientation-discrimination thresholds increased systematically from 7.4° to 11.3° according to the level of macular changes. In contrast, only 3 of 74 eyes exhibited abnormalities on the Amsler grid and central-field perimetric defects occurred with approximately equal probability at all grading levels. Conclusions In contrast to Amsler grid and central-visual-field testing, psychophysical orientation discrimination has the capability to distinguish between eyes with and without subtle age-related macular changes. PMID:19319009

Confocal laser endomicroscopy and ultrasound endoscopy during the same endoscopic session for diagnosis and staging of gastric neoplastic lesions.

PubMed

Gheorghe, C; Iacob, R; Dumbrava, Mona; Becheanu, G; Ionescu, M

2009-01-01

Confocal LASER endomicroscopy (CLE) is a newly developed endoscopic technique which allows subsurface in vivo histological assessment during ongoing endoscopy and targeted biopsies. Ultrasound endoscopy (EUS) is a useful tool in staging upper GI malignant lesions. We describe for the first time the use of both techniques during the same endoscopic session, in a pilot study, in order to increase the diagnostic yield of histological assessment and provide the staging of the gastric neoplastic lesions thus decreasing the time to therapeutic decision. CLE has been performed with the Pentax EG-3870CIK confocal endomicroscope after a 5 ml intravenous 10% fluorescein injection; EUS has been performed subsequently, during the same endoscopic Propofol sedation session, using a standard radial EUS-scope. Eleven patients have been investigated, 4 females, 7 males, mean age 59.7 +/- 12.3 years. The indication of CLE/EUS exploration was the presence of a gastric polypoid lesion in 37% of cases, atypical gastric ulcer in 27% of patients, gastric lymphoma 18%, suspicion of gastric cancer recurrence after resection 9% and infiltrating type gastric cancer 9%. Histological assessment after targeted biopsy has established the diagnosis of gastric adenocarcinoma in 55% of cases, gastric lymphoma in 18% of cases, gastric adenoma, gastric GIST and gastric foveolar hyperplasia in 9% of cases respectively. CLE has allowed targeted biopsies in 81.8% of cases. In 2 patients - one case with suspected recurrent gastric cancer after surgery and one case of gastric lymphoma, CLE has indicated normal gastric mucosa. The EUS evaluation has shown TO lesion in two cases, T1 in 3 cases, T2 in 3 cases, T3 in one case. The EUS evaluation showed in one gastric lymphoma patient a lesion interesting the mucosa and submucosa with regional adenopathy and a submucosal lesion with regional adenopathy in the other gastric lymphoma case. The therapeutic decision was surgery in 73% of cases, chemotherapy and

Compact energy dispersive X-ray microdiffractometer for diagnosis of neoplastic tissues

NASA Astrophysics Data System (ADS)

Sosa, C.; Malezan, A.; Poletti, M. E.; Perez, R. D.

2017-08-01

An energy dispersive X-ray microdiffractometer with capillary optics has been developed for characterizing breast cancer. The employment of low divergence capillary optics helps to reduce the setup size to a few centimeters, while providing a lateral spatial resolution of 100 μm. The system angular calibration and momentum transfer resolution were assessed by a detailed study of a polycrystalline reference material. The performance of the system was tested by means of the analysis of tissue-equivalent samples previously characterized by conventional X-ray diffraction. In addition, a simplified correction model for an appropriate comparison of the diffraction spectra was developed and validated. Finally, the system was employed to evaluate normal and neoplastic human breast samples, in order to determine their X-ray scatter signatures. The initial results indicate that the use of this compact energy dispersive X-ray microdiffractometer combined with a simplified correction procedure is able to provide additional information to breast cancer diagnosis.

Can early weight loss, eating behaviors and socioeconomic factors predict successful weight loss at 12- and 24-months in adolescents with obesity and insulin resistance participating in a randomised controlled trial?

PubMed

Gow, Megan L; Baur, Louise A; Ho, Mandy; Chisholm, Kerryn; Noakes, Manny; Cowell, Chris T; Garnett, Sarah P

2016-04-01

Lifestyle interventions in adolescents with obesity can result in weight loss following active intervention but individual responses vary widely. This study aimed to identify predictors of weight loss at 12- and 24-months in adolescents with obesity and clinical features of insulin resistance. Adolescents (n = 111, 66 girls, aged 10-17 years) were participants in a randomised controlled trial, the RESIST study, examining the effects of two diets differing in macronutrient content on insulin sensitivity. Eighty-five completed the 12-month program and 24-month follow-up data were available for 42 adolescents. Change in weight was determined by BMI expressed as a percentage of the 95th percentile (BMI95). The study physician collected socioeconomic data at baseline. Physical activity and screen time, and psychological dimensions of eating behavior were self-reported using the validated CLASS and EPI-C questionnaires, respectively. Stepwise multiple regressions were conducted to identify models that best predicted change in BMI95 at 12- and 24-months. Mean BMI95 was reduced at 12-months compared with baseline (mean difference [MD] ± SE: -6.9 ± 1.0, P < 0.001) but adolescents had significant re-gain from 12- to 24-months (MD ± SE: 3.7 ± 1.5, P = 0.017). Participants who achieved greater 12-month weight loss had: greater 3-month weight loss, a father with a higher education, lower baseline external eating and parental pressure to eat scores and two parents living at home. Participants who achieved greater 24-month weight loss had: greater 12-month weight loss and a lower baseline emotional eating score. Early weight loss is consistently identified as a strong predictor of long-term weight loss. This could be because early weight loss identifies those more motivated and engaged individuals. Patients who have baseline factors predictive of long-term weight loss failure may benefit from additional support during the intervention. Additionally

K-12 Postsecondary Alignment and School Accountability: Investigating High School Responses to California's Early Assessment Program

ERIC Educational Resources Information Center

Jackson, Jacob; Kurlaender, Michal

2016-01-01

State K-12 assessments may soon include measures for college readiness, as California's already do. We seek to understand how California's Early Assessment Program (EAP, designed to assess high school juniors' college readiness in English and math) may have influenced overall school-level college readiness and state accountability outcomes. Using…

Trajectories of prosocial behavior from adolescence to early adulthood: associations with personality change.

PubMed

Luengo Kanacri, Bernadette P; Pastorelli, Concetta; Eisenberg, Nancy; Zuffianò, Antonio; Castellani, Valeria; Caprara, Gian Vittorio

2014-07-01

The goal of this study was to identify heterogenic longitudinal patterns of change in prosocial behavior from adolescence to early adulthood and their association with change in Big Five Factor (BFF) personality traits from adolescence until early adulthood. Participants were 573 Italian adolescents aged approximately 13 at the first assessment and 21 at the last assessment. Using growth mixture modeling, low increasing (LI; 18%), medium quadratic (MQ; 26%), and high quadratic (HQ; 54%) trajectories of prosocial behavior were distinguished. Generally, the LI trajectory group predicted an increase in Conscientiousness over time, whereas the HQ trajectory group predicted greater change in Agreeableness and Openness. In addition, positive changes in Conscientiousness, Agreeableness, and Openness between ages 13 and 21 predicted a higher probability of belonging to the HQ prosocial group. Findings support a malleable perspective on personality and identify longterm positive pathways for youths' prosocial development. Copyright © 2014 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

A 12,000 year record of changes in herbivore niche separation and palaeoclimate (Wonderwerk Cave, South Africa)

NASA Astrophysics Data System (ADS)

Ecker, Michaela; Brink, James; Horwitz, Liora Kolska; Scott, Louis; Lee-Thorp, Julia A.

2018-01-01

The large mammalian fauna of southern Africa is characterised by strong niche separation into grazer and browser species, with few falling into the intermediate mixed-feeder niche. Moreover, the modern fauna is reduced in species diversity compared to the Pleistocene, following the extinction of several specialized grazers in the late Pleistocene and early Holocene. How did this state develop, and how might it be connected to climatic change during the Holocene? To better understand this development, we obtained extensive carbon and oxygen stable light isotope data from herbivore tooth enamel samples from Wonderwerk Cave, South Africa, spanning about 12,000-500 cal. BP. This is a unique dataset since it is the only site in the southern Kalahari with a robust chronometric record and well-preserved faunal remains for the last 12,000 years without significant gaps. Combining the stable isotopes with pollen and micromammal data from Wonderwerk Cave, we have explored shifts in the proportions of C3 and C4 plants and moisture availability. Although climate remained generally semi-arid for much of this period, the results show significant hydrological and vegetation shifts in the sequence, particularly with the strengthening of summer rainfall in the mid-Holocene. The results for the sixteen herbivore species reveal a reinforcement of the grazer-browser niche partitioning through the Holocene and shows how niche specialization follows changes in local vegetation composition. In the light of this reconstruction of the local ecology we discuss grazer extinctions, human adaptations, and the drivers behind climatic changes in the summer rainfall zone of southern Africa.

A first immunohistochemistry study of transketolase and transketolase-like 1 expression in canine hyperplastic and neoplastic mammary lesions.

PubMed

Burrai, Giovanni Pietro; Tanca, Alessandro; Cubeddu, Tiziana; Abbondio, Marcello; Polinas, Marta; Addis, Maria Filippa; Antuofermo, Elisabetta

2017-01-31

Canine mammary tumors represent the most common neoplasm in female dogs, and the discovery of cancer biomarkers and their translation to clinical relevant assays is a key requirement in the war on cancer. Since the description of the 'Warburg effect', the reprogramming of metabolic pathways is considered a hallmark of pathological changes in cancer cells. In this study, we investigate the expression of two cancer-related metabolic enzymes, transketolase (TKT) and transketolase-like 1 (TKTL1), involved in the pentose phosphate pathway (PPP), an alternative metabolic pathway for glucose breakdown that could promote cancer by providing the precursors and energy required for rapidly growing cells. TKT and TKTL1 protein expression was investigated by immunohistochemistry in canine normal (N = 6) and hyperplastic glands (N = 3), as well as in benign (N = 11) and malignant mammary tumors (N = 17). TKT expression was higher in hyperplastic lesions and in both benign and malignant tumors compared to the normal mammary gland, while TKTL1 levels were remarkably higher in hyperplastic lesions, simple adenomas and simple carcinomas than in the normal mammary glands (P < 0.05). This study reveals that the expression of a key PPP enzyme varies along the evolution of canine mammary neoplastic lesions, and supports a role of metabolic changes in the development of canine mammary tumors.

Use of a nitinol stent to palliate a colorectal neoplastic obstruction in a dog

PubMed Central

Culp, William T. N.; MacPhail, Catriona M.; Perry, James A.; Jensen, Tracey D.

2015-01-01

Case Description A 12-year-old castrated male Labrador Retriever was evaluated for clinical signs associated with colorectal obstruction. Clinical Findings The dog had a 2-week history of tenesmus and hematochezia. On rectal examination, an annular colorectal mass was palpable extending orad into the pelvic canal. The original diagnosis of the colorectal mass was a mucosal adenoma. The dog was maintained on a low-residue diet and fecal softeners for a period of 13 months after initial diagnosis. At that time, medical management was no longer effective. Treatment and Outcome Placement of a colonic stent was chosen to palliate the clinical signs associated with colorectal obstruction. By use of fluoroscopic and colonoscopic guidance, a nitinol stent was placed intraluminally to open the obstructed region. Placement of the stent resulted in improvement of clinical signs, although tenesmus and obstipation occurred periodically after stent placement. At 212 days after stent placement, the patient had extensive improvement in clinical signs with minimal complications; however, clinical signs became severe at 238 days after stent placement, and the dog was euthanized. Histologic evaluation of the rectal tumor from samples obtained during necropsy revealed that the tumor had undergone malignant transformation to a carcinoma in situ. Clinical Relevance A stent was successfully placed in the colon and rectum to relieve obstruction associated with a tumor originally diagnosed as a benign neoplasm. Placement of colorectal stents may be an option for the palliation of colorectal obstruction secondary to neoplastic disease; however, clinical signs may persist, and continuation of medical management may be necessary. PMID:21756178

Changes in nurses' decision making during a 12-h day shift.

PubMed

McClelland, L E; Switzer, F S; Pilcher, J J

2013-01-01

Although shift work is necessary in many health-care settings, research suggests that it can have detrimental effects on performance in health-care providers. To determine if a change in decision-making occurred across a 12-h day shift in a sample of registered nurses. The participants were nurses working a 12-h day shift (7 a.m.-7 p.m.) at a large hospital in the south-eastern USA. Participants completed a policy-capturing questionnaire, examining their likelihood of calling a physician in response to specific patient symptoms, at the beginning and end of the shift. They also completed self-report surveys on alertness, stress and sleepiness. Sixty-five nurses completed the study, an overall response rate of 41%. Participants significantly changed their decision-making policies from the beginning to the end of the work shift and also became significantly less alert and more stressed. However, there was no correlation between decision-making and reported alertness and stress. These results suggest that medical judgment in registered nurses changed from the beginning to the end of a 12-h day shift. One possible underlying mechanism responsible for the changes seen across the shift could be the ability to maintain attention, as suggested by the Controlled Attention Model. The current results expand upon previous research, indicating there are a variety of negative outcomes associated with shift work.

The development of functional network organization in early childhood and early adolescence: A resting-state fNIRS study.

PubMed

Cai, Lin; Dong, Qi; Niu, Haijing

2018-04-01

Early childhood (7-8 years old) and early adolescence (11-12 years old) constitute two landmark developmental stages that comprise considerable changes in neural cognition. However, very limited information from functional neuroimaging studies exists on the functional topological configuration of the human brain during specific developmental periods. In the present study, we utilized continuous resting-state functional near-infrared spectroscopy (rs-fNIRS) imaging data to examine topological changes in network organization during development from early childhood and early adolescence to adulthood. Our results showed that the properties of small-worldness and modularity were not significantly different across development, demonstrating the developmental maturity of important functional brain organization in early childhood. Intriguingly, young children had a significantly lower global efficiency than early adolescents and adults, which revealed that the integration of the distributed networks strengthens across the developmental stages underlying cognitive development. Moreover, local efficiency of young children and adolescents was significantly lower than that of adults, while there was no difference between these two younger groups. This finding demonstrated that functional segregation remained relatively steady from early childhood to early adolescence, and the brain in these developmental periods possesses no optimal network configuration. Furthermore, we found heterogeneous developmental patterns in the regional nodal properties in various brain regions, such as linear increased nodal properties in the frontal cortex, indicating increasing cognitive capacity over development. Collectively, our results demonstrated that significant topological changes in functional network organization occurred during these two critical developmental stages, and provided a novel insight into elucidating subtle changes in brain functional networks across development. Copyright �

Changes in the Staphylococcus aureus Transcriptome during Early Adaptation to the Lung

PubMed Central

Chaffin, Donald O.; Taylor, Destry; Skerrett, Shawn J.; Rubens, Craig E.

2012-01-01

Staphylococcus aureus is a common inhabitant of the human nasopharynx. It is also a cause of life-threatening illness, producing a potent array of virulence factors that enable survival in normally sterile sites. The transformation of S. aureus from commensal to pathogen is poorly understood. We analyzed S. aureus gene expression during adaptation to the lung using a mouse model of S. aureus pneumonia. Bacteria were isolated by bronchoalveolar lavage after residence in vivo for up to 6 hours. S. aureus in vivo RNA transcription was compared by microarray to that of shake flask grown stationary phase and early exponential phase cells. Compared to in vitro conditions, the in vivo transcriptome was dramatically altered within 30 minutes. Expression of central metabolic pathways changed significantly in response to the lung environment. Gluconeogenesis (fbs, pckA) was down regulated, as was TCA cycle and fermentation pathway gene expression. Genes associated with amino acid synthesis, RNA translation and nitrate respiration were upregulated, indicative of a highly active metabolic state during the first 6 hours in the lung. Virulence factors regulated by agr were down regulated in vivo and in early exponential phase compared to stationary phase cells. Over time in vivo, expression of ahpCF, involved in H2O2 scavenging, and uspA, which encodes a universal stress regulator, increased. Transcription of leukotoxic α and β-type phenol-soluble modulins psmα1-4 and psmβ1-2 increased 13 and 8-fold respectively; hld mRNA, encoding δ-hemolysin, was increased 9-fold. These were the only toxins to be significantly upregulated in vivo. These data provide the first complete survey of the S. aureus transcriptome response to the mammalian airway. The results present intriguing contrasts with previous work in other in vitro and in vivo models and provide novel insights into the adaptive and temporal response of S. aureus early in the pathogenesis of pneumonia. PMID:22876285

Frameworks for Change: Four Recurrent Themes for Quality in Early Childhood Curriculum Initiatives

ERIC Educational Resources Information Center

Burgess, Jennifer; Fleet, Alma

2009-01-01

This paper reports on the first phase of a case study that investigated how early childhood teachers experience organisational change. As one of three levels of quality improvement, State government-funded curriculum initiatives were developed with an aim to promote change. Three curriculum documents, one each focusing on literacy, pedagogy and…

[Relationship between body weight status in early adulthood and body weight change at middle age in adults and type 2 diabetes mellitus].

PubMed

Zhou, Long; Zhao, Liancheng; Li, Ying; Guo, Min; Wu, Yangfeng

2016-03-01

To explore the relationship between weight status in early adulthood and body weight change at middle age in adults and type 2 diabetes mellitus (T2DM). The data of 14 population samples from China Multicenter Collaborative Study of Cardiovascular Epidemiology conducted in 1998 were used. Approximately 1 000 men and women in each sample were surveyed for cardiovascular disease risk factors, including body weight at age 25 years. The body mass index (BMI) at the age 25 years was calculated. The association between body weight in early adulthood and body weight change at middle age and T2DM was examined by using logistic regression model. The incidence of T2DM in low weight group (BMI<18.5 kg/m(2)), normal weight group (BMI: 18.5-23.9 kg/m(2)), overweight group (BMI: 24.0-27.9 kg/m(2)) and obese group (BMI:≥28.0 kg/m(2)) at 25 years old were 2.4%(30/1263), 2.8%(266/9562), 4.0%(70/1739) and 6.4% (7/110), respectively (P value for trend<0.01). The incidence of T2DM for adults with weight change <-7.5 kg, -7.5--2.6 kg, -2.5-2.5 kg, 2.6-7.5 kg, 7.6-12.5 kg and >12.5 kg at middle age were 2.5% (18/712), 1.3%(21/1629), 2.1%(48/2330), 2.3%(59/2585), 3.7%(94/2518), and 4.6% (133/2900) respectively. (P value for trend <0.01), Multivariate logistic regression analysis showed that overweight and obesity at age 25 years and subsequent weight gain were positively correlated with T2DM after adjusted other risk factors (all P values for trend <0.01). Overweight and obesity in early adulthood and weight gain at middle age were both independently associated with the increased risk of T2DM in middle-aged men and women.

12 CFR 205.8 - Change in terms notice; error resolution notice.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 2 2011-01-01 2011-01-01 false Change in terms notice; error resolution notice. 205.8 Section 205.8 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM ELECTRONIC FUND TRANSFERS (REGULATION E) § 205.8 Change in terms notice; error resolution notice...

12 CFR 205.8 - Change in terms notice; error resolution notice.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 2 2010-01-01 2010-01-01 false Change in terms notice; error resolution notice. 205.8 Section 205.8 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM ELECTRONIC FUND TRANSFERS (REGULATION E) § 205.8 Change in terms notice; error resolution notice...

8 CFR 338.12 - Endorsement by clerk of court in case name is changed.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Endorsement by clerk of court in case name is changed. 338.12 Section 338.12 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY NATIONALITY... database for naturalization recordkeeping, the name change information will be maintained in that database...

The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms.

PubMed

Bavik, Claes; Coleman, Ilsa; Dean, James P; Knudsen, Beatrice; Plymate, Steven; Nelson, Peter S

2006-01-15

The greatest risk factor for developing carcinoma of the prostate is advanced age. Potential molecular and physiologic contributors to the frequency of cancer occurrence in older individuals include the accumulation of somatic mutations through defects in genome maintenance, epigenetic gene silencing, oxidative stress, loss of immune surveillance, telomere dysfunction, chronic inflammation, and alterations in tissue microenvironment. In this context, the process of prostate carcinogenesis can be influenced through interactions between intrinsic cellular alterations and the extrinsic microenvironment and macroenvironment, both of which change substantially as a consequence of aging. In this study, we sought to characterize the molecular alterations that occur during the process of prostate fibroblast senescence to identify factors in the aged tissue microenvironment capable of promoting the proliferation and potentially the neoplastic progression of prostate epithelium. We evaluated three mechanisms leading to cell senescence: oxidative stress, DNA damage, and replicative exhaustion. We identified a consistent program of gene expression that includes a subset of paracrine factors capable of influencing adjacent prostate epithelial growth. Both direct coculture and conditioned medium from senescent prostate fibroblasts stimulated epithelial cell proliferation, 3-fold and 2-fold, respectively. The paracrine-acting proteins fibroblast growth factor 7, hepatocyte growth factor, and amphiregulin (AREG) were elevated in the extracellular environment of senescent prostate fibroblasts. Exogenous AREG alone stimulated prostate epithelial cell growth, and neutralizing antibodies and small interfering RNA targeting AREG attenuated, but did not completely abrogate the growth-promoting effects of senescent fibroblast conditioned medium. These results support the concept that aging-related changes in the prostate microenvironment may contribute to the progression of prostate

Immunohistochemical characterization of neoplastic cells of breast origin.

PubMed

Noriega, Mariadelasmercedes; Paesani, Fernando; Perazzo, Florencia; Lago, Néstor; Krupitzki, Hugo; Nieto, Silvana; Garcia, Alejandro; Avagnina, Alejandra; Elsner, Boris; Denninghoff, Valeria Cecilia

2012-06-22

After skin cancer, breast cancer is the most common malignancy in women. Tumors of unknown origin account for 5-15% of malignant neoplasms, with 1.5% being breast cancer. An immunohistochemical panel with conventional and newer markers, such as mammaglobin, was selected for the detection of neoplastic cells of breast origin. The specific objectives are: 1) to determine the sensitivity and specificity of the panel, with a special emphasis on the inclusion of the mammaglobin marker, and 2) to compare immunohistochemistry performed on whole tissue sections and on tissue micro-array. Twenty-nine metastatic breast tumors were included and assumed as tumors of unknown origin. Other 48 biopsies of diverse tissues were selected and assumed as negative controls. Tissue Micro-Array was performed. Immunohistochemistry for mammaglobin, gross cystic disease fluid protein-15, estrogen receptor, progesterone receptor and cytokeratin 7 was done. Mammaglobin positive staining was observed in 10/29 cases, in 13/29 cases for gross cystic disease fluid protein-15, in 20/29 cases for estrogen receptor, in 9/29 cases for progesterone receptor, and in 25/29 cases for cytokeratin 7. Among the negative controls, mammaglobin was positive in 2/48, and gross cystic disease fluid protein-15 in 4/48. The inclusion of MAG antibody in the immunohistochemical panel for the detection of tumors of unknown origin contributed to the detection of metastasis of breast cancer. The diagnostic strategy with the highest positive predictive value (88%) included hormone receptors and mammaglobin in serial manner.

Effects of saxagliptin on early microvascular changes in patients with type 2 diabetes

PubMed Central

2014-01-01

Background Patients with diabetes mellitus are at increased risk for microvascular complications. Early changes in microcirculation are characterized by hyperperfusion (e.g. in the retina and kidney) and increased pulse wave reflection leading to increased aortic pressure. We investigated the effects of the DPP-4-inhibitor saxagliptin on early retinal microvascular changes. Methods In this double-blind, controlled, cross-over trial 50 patients (without clinical signs of microvascular alterations) with type-2 diabetes (mean duration of 4 years) were randomized to receive placebo or 5 mg saxagliptin for 6 weeks. Retinal arteriolar structure and retinal capillary flow (RCF) at baseline and during flicker-light exposure was assessed by scanning laser Doppler flowmetry. Central hemodynamics were assessed by pulse wave analysis. Results Postprandial blood glucose (9.27 ± 0.4 versus 10.1 ± 0.4 mmol/L; p = 0.001) and HbA1c (6.84 ± 0.15 (51 ± 1.6) versus 7.10 ± 0.17% (54 ± 1.9 mmol/mol); p < 0.001) were significantly reduced with saxagliptin treatment compared to placebo. RCF was significantly reduced after treatment with saxagliptin (288 ± 13.2 versus 314 ± 14.1 AU; p = 0.033). This was most pronounced in a subgroup of patients (n = 32) with a fall in postprandial blood glucose (280 ± 12.1 versus 314 ± 16.6 AU; p = 0.011). No significant changes in RCF were seen during flicker-light exposure between placebo and saxagliptin, but the vasodilatory capacity increased two-fold with saxagliptin treatment. Central augmentation pressure tended to be lower after treatment with saxagliptin (p = 0.094), and central systolic blood pressure was significantly reduced (119 ± 2.3 versus 124 ± 2.3 mmHg; p = 0.038). Conclusions Our data suggest that treatment with saxagliptin for 6 weeks normalizes retinal capillary flow and improves central hemodynamics in type-2 diabetes. Trial registration The

Effects of saxagliptin on early microvascular changes in patients with type 2 diabetes.

PubMed

Ott, Christian; Raff, Ulrike; Schmidt, Stephanie; Kistner, Iris; Friedrich, Stefanie; Bramlage, Peter; Harazny, Joanna M; Schmieder, Roland E

2014-01-14

Patients with diabetes mellitus are at increased risk for microvascular complications. Early changes in microcirculation are characterized by hyperperfusion (e.g. in the retina and kidney) and increased pulse wave reflection leading to increased aortic pressure. We investigated the effects of the DPP-4-inhibitor saxagliptin on early retinal microvascular changes. In this double-blind, controlled, cross-over trial 50 patients (without clinical signs of microvascular alterations) with type-2 diabetes (mean duration of 4 years) were randomized to receive placebo or 5 mg saxagliptin for 6 weeks. Retinal arteriolar structure and retinal capillary flow (RCF) at baseline and during flicker-light exposure was assessed by scanning laser Doppler flowmetry. Central hemodynamics were assessed by pulse wave analysis. Postprandial blood glucose (9.27 ± 0.4 versus 10.1 ± 0.4 mmol/L; p = 0.001) and HbA1c (6.84 ± 0.15 (51 ± 1.6) versus 7.10 ± 0.17% (54 ± 1.9 mmol/mol); p < 0.001) were significantly reduced with saxagliptin treatment compared to placebo. RCF was significantly reduced after treatment with saxagliptin (288 ± 13.2 versus 314 ± 14.1 AU; p = 0.033). This was most pronounced in a subgroup of patients (n = 32) with a fall in postprandial blood glucose (280 ± 12.1 versus 314 ± 16.6 AU; p = 0.011). No significant changes in RCF were seen during flicker-light exposure between placebo and saxagliptin, but the vasodilatory capacity increased two-fold with saxagliptin treatment. Central augmentation pressure tended to be lower after treatment with saxagliptin (p = 0.094), and central systolic blood pressure was significantly reduced (119 ± 2.3 versus 124 ± 2.3 mmHg; p = 0.038). Our data suggest that treatment with saxagliptin for 6 weeks normalizes retinal capillary flow and improves central hemodynamics in type-2 diabetes. The study was registered at (ID: NCT01319357).

Enhanced neoplastic transformation by mammography X rays relative to 200 kVp X rays: indication for a strong dependence on photon energy of the RBE(M) for various end points.

PubMed

Frankenberg, D; Kelnhofer, K; Bär, K; Frankenberg-Schwager, M

2002-01-01

The fundamental assumption implicit in the use of the atomic bomb survivor data to derive risk estimates is that the gamma rays of Hiroshima and Nagasaki are considered to have biological efficiencies equal to those of other low-LET radiations up to 10 keV/microm, including mammography X rays. Microdosimetric and radiobiological data contradict this assumption. It is therefore of scientific and public interest to evaluate the efficiency of mammography X rays (25-30 kVp) to induce cancer. In this study, the efficiency of mammography X rays relative to 200 kVp X rays to induce neoplastic cell transformation was evaluated using cells of a human hybrid cell line (CGL1). For both radiations, a linear-quadratic dose-effect relationship was observed for neoplastic transformation of CGL1 cells; there was a strong linear component for the 29 kVp X rays. The RBE(M) of mammography X rays relative to 200 kVp X rays was determined to be about 4 for doses < or = 0.5 Gy. A comparison of the electron fluences for both X rays provides strong evidence that electrons with energies of < or = 15 keV can induce neoplastic transformation of CGL1 cells. Both the data available in the literature and the results of the present study strongly suggest an increase of RBE(M) for carcinogenesis in animals, neoplastic cell transformation, and clastogenic effects with decreasing photon energy or increasing LET to an RBE(M) approximately 8 for mammography X rays relative to 60Co gamma rays.

Magnetic Resonance Imaging to Detect Early Molecular and Cellular Changes in Alzheimer's Disease.

PubMed

Knight, Michael J; McCann, Bryony; Kauppinen, Risto A; Coulthard, Elizabeth J

2016-01-01

Recent pharmaceutical trials have demonstrated that slowing or reversing pathology in Alzheimer's disease is likely to be possible only in the earliest stages of disease, perhaps even before significant symptoms develop. Pathology in Alzheimer's disease accumulates for well over a decade before symptoms are detected giving a large potential window of opportunity for intervention. It is therefore important that imaging techniques detect subtle changes in brain tissue before significant macroscopic brain atrophy. Current diagnostic techniques often do not permit early diagnosis or are too expensive for routine clinical use. Magnetic Resonance Imaging (MRI) is the most versatile, affordable, and powerful imaging modality currently available, being able to deliver detailed analyses of anatomy, tissue volumes, and tissue state. In this mini-review, we consider how MRI might detect patients at risk of future dementia in the early stages of pathological change when symptoms are mild. We consider the contributions made by the various modalities of MRI (structural, diffusion, perfusion, relaxometry) in identifying not just atrophy (a late-stage AD symptom) but more subtle changes reflective of early dementia pathology. The sensitivity of MRI not just to gross anatomy but to the underlying "health" at the cellular (and even molecular) scales, makes it very well suited to this task.

IL-12 Can Target Human Lung Adenocarcinoma Cells and Normal Bronchial Epithelial Cells Surrounding Tumor Lesions

PubMed Central

Airoldi, Irma; Di Carlo, Emma; Cocco, Claudia; Caci, Emanuela; Cilli, Michele; Sorrentino, Carlo; Sozzi, Gabriella; Ferrini, Silvano; Rosini, Sandra; Bertolini, Giulia; Truini, Mauro; Grossi, Francesco; Galietta, Luis Juan Vicente; Ribatti, Domenico; Pistoia, Vito

2009-01-01

Background Non small cell lung cancer (NSCLC) is a leading cause of cancer death. We have shown previously that IL-12rb2 KO mice develop spontaneously lung adenocarcinomas or bronchioalveolar carcinomas. Aim of the study was to investigate i) IL-12Rβ2 expression in human primary lung adenocarcinomas and in their counterparts, i.e. normal bronchial epithelial cells (NBEC), ii) the direct anti-tumor activity of IL-12 on lung adenocarcinoma cells in vitro and vivo, and the mechanisms involved, and iii) IL-12 activity on NBEC. Methodology/Principal Findings Stage I lung adenocarcinomas showed significantly (P = 0.012) higher frequency of IL-12Rβ2 expressing samples than stage II/III tumors. IL-12 treatment of IL-12R+ neoplastic cells isolated from primary adenocarcinoma (n = 6) inhibited angiogenesis in vitro through down-regulation of different pro-angiogenic genes (e.g. IL-6, VEGF-C, VEGF-D, and laminin-5), as assessed by chorioallantoic membrane (CAM) assay and PCR array. In order to perform in vivo studies, the Calu6 NSCLC cell line was transfected with the IL-12RB2 containing plasmid (Calu6/β2). Similar to that observed in primary tumors, IL-12 treatment of Calu6/β2+ cells inhibited angiogenesis in vitro. Tumors formed by Calu6/β2 cells in SCID/NOD mice, inoculated subcutaneously or orthotopically, were significantly smaller following IL-12 vs PBS treatment due to inhibition of angiogenesis, and of IL-6 and VEGF-C production. Explanted tumors were studied by histology, immuno-histochemistry and PCR array. NBEC cells were isolated and cultured from lung specimens of non neoplastic origin. NBEC expressed IL-12R and released constitutively tumor promoting cytokines (e.g. IL-6 and CCL2). Treatment of NBEC with IL-12 down-regulated production of these cytokines. Conclusions This study demonstrates that IL-12 inhibits directly the growth of human lung adenocarcinoma and targets the adjacent NBEC. These novel anti-tumor activities of IL-12 add to the well

Association between the change in body mass index from early adulthood to midlife and subsequent type 2 diabetes mellitus.

PubMed

Sun, Wanwan; Shi, Lixin; Ye, Zhen; Mu, Yiming; Liu, Chao; Zhao, Jiajun; Chen, Lulu; Li, Qiang; Yang, Tao; Yan, Li; Wan, Qin; Wu, Shengli; Liu, Yan; Wang, Guixia; Luo, Zuojie; Tang, Xulei; Chen, Gang; Huo, Yanan; Gao, Zhengnan; Su, Qing; Wang, Youmin; Qin, Guijun; Deng, Huacong; Yu, Xuefeng; Shen, Feixia; Chen, Li; Zhao, Liebin; Sun, Jichao; Ding, Lin; Xu, Yu; Xu, Min; Dai, Meng; Wang, Tiange; Zhang, Di; Lu, Jieli; Bi, Yufang; Lai, Shenghan; Li, Donghui; Wang, Weiqing; Ning, Guang

2016-03-01

To clarify the quantitative relationship of body mass index (BMI) change from early adulthood to midlife with presence of type 2 diabetes mellitus (T2DM) after midlife. This study included 120,666 middle-aged and elderly, whose retrospectively self-reported body weight at 20 and 40 years and measured height were available. BMI at 20 and 40 years and BMI change in between were defined as early-adulthood BMI, midlife BMI, and early-adulthood BMI change. The odds ratio (OR) for T2DM associated with an 1-unit increment of early-adulthood or midlife BMI was 1.08 (95% confidence interval (CI), 1.07-1.08) and 1.09 (95% CI, 1.09-1.10) respectively. In the cross-tabulation of both early-adulthood BMI and BMI change, the prevalence of T2DM increased across both variables. Compared with participants with normal early-adulthood weight and BMI increase/decrease ≤1, the OR (95% CI) for T2DM of participants with early-adulthood overweight/obesity and BMI increase ≥4 kg/m(2) was 3.49 (3.05-4.00). For participants with early-adulthood underweight and BMI increase/decrease ≤ 1, the OR (95% CI) was 0.85 (0.75-0.97). Subgroup analysis according to sex and age showed similar trends. Early-adulthood BMI may influence T2DM prevalence after midlife independent of current BMI. T2DM prevalence after midlife was positively associated with early-adulthood weight gain and inversely related to early-adulthood weight loss, while early-adulthood weight loss could not completely negate the adverse effect of early-adulthood overweight/obesity on diabetes. © 2016 The Obesity Society.

Precursors of social emotional functioning among full-term and preterm infants at 12 months: Early infant withdrawal behavior and symptoms of maternal depression.

PubMed

Moe, Vibeke; Braarud, Hanne Cecilie; Wentzel-Larsen, Tore; Slinning, Kari; Vannebo, Unni Tranaas; Guedeney, Antoine; Heimann, Mikael; Rostad, Anne Margrethe; Smith, Lars

2016-08-01

This study forms part of a longitudinal investigation of early infant social withdrawal, maternal symptoms of depression and later child social emotional functioning. The sample consisted of a group of full-term infants (N=238) and their mothers, and a group of moderately premature infants (N=64) and their mothers. At 3 months, the infants were observed with the Alarm Distress Baby Scale (ADBB) and the mothers completed the Edinburgh Postnatal Depression Scale (EPDS). At 12 months, the mothers filled out questionnaires about the infants' social emotional functioning (Infant Toddler Social Emotional Assessment and the Ages and Stages Questionnaire-Social Emotional). At 3 months, as we have previously shown, the premature infants had exhibited more withdrawal behavior and their mothers reported elevated maternal depressive symptoms as compared with the full-born group. At 12 months the mothers of the premature infants reported more child internalizing behavior. These data suggest that infant withdrawal behavior as well as maternal depressive mood may serve as sensitive indices of early risk status. Further, the results suggest that early maternal depressive symptoms are a salient predictor of later child social emotional functioning. However, neither early infant withdrawal behavior, nor gestational age, did significantly predict social emotional outcome at 12 months. It should be noted that the differences in strength of the relations between ADBB and EPDS, respectively, to the outcome at 12 months was modest. An implication of the study is that clinicians should be aware of the complex interplay between early infant withdrawal and signs of maternal postpartum depression in planning ports of entry for early intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

Early postoperative changes in cerebral oxygen metabolism following neonatal cardiac surgery: Effects of surgical duration

PubMed Central

Buckley, Erin M.; Lynch, Jennifer M.; Goff, Donna A.; Schwab, Peter J.; Baker, Wesley B.; Durduran, Turgut; Busch, David R.; Nicolson, Susan C.; Montenegro, Lisa M.; Naim, Maryam Y.; Xiao, Rui; Spray, Thomas L.; Yodh, A. G.; Gaynor, J. William; Licht, Daniel J.

2013-01-01

Objective The early postoperative period following neonatal cardiac surgery is a time of increased risk for brain injury, yet the mechanisms underlying this risk are unknown. To understand these risks more completely, we quantified changes in postoperative cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood flow (CBF) compared with preoperative levels by using noninvasive optical modalities. Methods Diffuse optical spectroscopy and diffuse correlation spectroscopy were used concurrently to derive cerebral blood flow and oxygen utilization postoperatively for 12 hours. Relative changes in CMRO2, OEF, and CBF were quantified with reference to preoperative data. A mixed-effect model was used to investigate the influence of total support time and deep hypothermic circulatory arrest duration on relative changes in CMRO2, OEF, and CBF. Results Relative changes in CMRO2, OEF, and CBF were assessed in 36 patients, 21 with single-ventricle defects and 15 with 2-ventricle defects. Among patients with single-ventricle lesions, deep hypothermic circulatory arrest duration did not affect relative changes in CMRO2, CBF, or OEF (P > .05). Among 2-ventricle patients, total support time was not a significant predictor of relative changes in CMRO2 or CBF (P > .05), although longer total support time was associated significantly with greater increases in relative change of postoperative OEF (P = .008). Conclusions Noninvasive diffuse optical techniques were used to quantify postoperative relative changes in CMRO2, CBF, and OEF for the first time in this observational pilot study. Pilot data suggest that surgical duration does not account for observed variability in the relative change in CMRO2, and that more comprehensive clinical studies using the new technology are feasible and warranted to elucidate these issues further. PMID:23111021

Experienced Early Childhood Teachers as Graduate Students: A Process of Change

ERIC Educational Resources Information Center

Mevorach, Miriam; Miron, Mordechai

2011-01-01

This paper explores perceptions of professional identity among experienced early childhood educators (ECEs) who are novice students in a new master's degree program in ECE. We sought to examine the changes experienced by these educators. The study used qualitative content analysis, which included an open-ended questionnaire that was administered…

Massachusetts Early Warning Indicator System (EWIS). "Technical Descriptions of Risk Model Development": Middle and High School Age Groupings (Grades 7-12)

ERIC Educational Resources Information Center

Massachusetts Department of Elementary and Secondary Education, 2013

2013-01-01

The Massachusetts Department of Elementary and Secondary Education (Department) created the grades 1-12 Early Warning Indicator System (EWIS) in response to district interest in the Early Warning Indicator Index (EWII) that the Department previously created for rising grade 9 students. Districts shared that the EWII data were helpful, but also…

Long-term follow up of gallbladder polyps.

PubMed

Park, Jeong Youp; Hong, Sung Pil; Kim, Yoon Jae; Kim, Hong Jeoung; Kim, Hee Man; Cho, Jae Hee; Park, Seung Woo; Song, Si Young; Chung, Jae Bock; Bang, Seungmin

2009-02-01

The management of gallbladder polyps (GBP) is directly linked to the early diagnosis of gallbladder cancer (GBC). This study aimed to evaluate the malignant risk of GBP. In total, 1558 patients diagnosed with GBP were followed. Neoplastic polyps were defined as GBC and its premalignant lesions. The risk for malignancy was estimated with the cumulative detection rate of neoplastic polyps. Thirty-three cases (2.1%) were diagnosed with neoplastic polyps. The cumulative detection rates of neoplastic polyps were 1.7% at 1 year, 2.8% at 5 years, and 4% at 8 years after diagnosis. The size of GBP and the presence of gallstones were risk factors for neoplastic polyps. Polyps > or = 10 mm had a 24.2 times greater risk of malignancy than polyps < 10 mm. However, 15 of 33 neoplastic polyps (45.5%) were < 10 mm at the time of diagnosis of GBP. During follow up in 36 (3.5%) of 1027 cases, an increase in size was detected; of these, nine (25%) had neoplastic polyps. Even small polyps have a risk of malignancy, and careful long-term follow up of GBP will help detect and treat early GBC.

Confocal fluorescence microscopy to evaluate changes in adipocytes in the tumor microenvironment associated with invasive ductal carcinoma and ductal carcinoma in situ.

PubMed

Dobbs, Jessica L; Shin, Dongsuk; Krishnamurthy, Savitri; Kuerer, Henry; Yang, Wei; Richards-Kortum, Rebecca

2016-09-01

Adipose tissue is a dynamic organ that provides endocrine, inflammatory and angiogenic factors, which can assist breast carcinoma cells with invasion and metastasis. Previous studies have shown that adipocytes adjacent to carcinoma, known as cancer-associated adipocytes, undergo extensive changes that correspond to an "activated phenotype," such as reduced size relative to adipocytes in non-neoplastic breast tissue. Optical imaging provides a tool that can be used to characterize adipocyte morphology and other features of the tumor microenvironment. In this study, we used confocal fluorescence microscopy to acquire images of freshly excised breast tissue stained topically with proflavine. We developed a computerized algorithm to identify and quantitatively measure phenotypic properties of adipocytes located adjacent to and far from normal collagen, ductal carcinoma in situ and invasive ductal carcinoma. Adipocytes were measured in confocal fluorescence images of fresh breast tissue collected from 22 patients. Results show that adipocytes adjacent to neoplastic tissue margins have significantly smaller area compared to adipocytes far from the margins of neoplastic lesions and compared to adipocytes adjacent to non-neoplastic collagenous stroma. These findings suggest that confocal microscopic images can be utilized to evaluate phenotypic properties of adipocytes in breast stroma which may be useful in defining alterations in microenvironment that may aid in the development and progression of neoplastic lesions. © 2016 UICC.

Cortical Thickness Change in Autism during Early Childhood

PubMed Central

Smith, Elizabeth; Thurm, Audrey; Greenstein, Deanna; Farmer, Cristan; Swedo, Susan; Giedd, Jay; Raznahan, Armin

2016-01-01

Structural magnetic resonance imaging (MRI) scans at high spatial resolution can detect potential foci of early brain dysmaturation in children with autism spectrum disorders (ASD). In addition, comparison between MRI and behavior measures over time can identify patterns of brain change accompanying specific outcomes. We report structural MRI data from two time points for a total of 84 scans in children with ASD and 30 scans in typical controls (mean age time one=4.1 years, mean age at time two=6.6 years). Surface-based cortical morphometry and linear mixed effects models were used to link changes in cortical anatomy to both diagnostic status and individual differences in changes in language and autism severity. Compared to controls, children with ASD showed accelerated gray matter volume gain with age, which was driven by a lack of typical age-related cortical thickness (CT) decrease within ten cortical regions involved in language, social cognition and behavioral control. Greater expressive communication gains with age in children with ASD were associated with greater CT gains in a set of right hemisphere homologues to dominant language cortices, potentially identifying a compensatory system for closer translational study. PMID:27061356

Early Cellular Changes in the Ascending Aorta and Myocardium in a Swine Model of Metabolic Syndrome.

PubMed

Saraf, Rabya; Huang, Thomas; Mahmood, Feroze; Owais, Khurram; Bardia, Amit; Khabbaz, Kamal R; Liu, David; Senthilnathan, Venkatachalam; Lassaletta, Antonio D; Sellke, Frank; Matyal, Robina

2016-01-01

Metabolic syndrome is associated with pathological remodeling of the heart and adjacent vessels. The early biochemical and cellular changes underlying the vascular damage are not fully understood. In this study, we sought to establish the nature, extent, and initial timeline of cytochemical derangements underlying reduced ventriculo-arterial compliance in a swine model of metabolic syndrome. Yorkshire swine (n = 8 per group) were fed a normal diet (ND) or a high-cholesterol (HCD) for 12 weeks. Myocardial function and blood flow was assessed before harvesting the heart. Immuno-blotting and immuno-histochemical staining were used to assess the cellular changes in the myocardium, ascending aorta and left anterior descending artery (LAD). There was significant increase in body mass index, blood glucose and mean arterial pressures (p = 0.002, p = 0.001 and p = 0.024 respectively) in HCD group. At the cellular level there was significant increase in anti-apoptotic factors p-Akt (p = 0.007 and p = 0.002) and Bcl-xL (p = 0.05 and p = 0.01) in the HCD aorta and myocardium, respectively. Pro-fibrotic markers TGF-β (p = 0.01), pSmad1/5 (p = 0.03) and MMP-9 (p = 0.005) were significantly increased in the HCD aorta. The levels of pro-apoptotic p38MAPK, Apaf-1 and cleaved Caspase3 were significantly increased in aorta of HCD (p = 0.03, p = 0.04 and p = 0.007 respectively). Similar changes in coronary arteries were not observed in either group. Functionally, the high cholesterol diet resulted in significant increase in ventricular end systolic pressure and-dp/dt (p = 0.05 and p = 0.007 respectively) in the HCD group. Preclinical metabolic syndrome initiates pro-apoptosis and pro-fibrosis pathways in the heart and ascending aorta, while sparing coronary arteries at this early stage of dietary modification.

Impacts of Early Summer Eurasian Snow Cover Change on Atmospheric Circulation in Northern Mid-Latitudes

NASA Astrophysics Data System (ADS)

Nozawa, T.

2016-12-01

Recently, Japan Aerospace Exploration Agency (JAXA) has developed a new long-term snow cover extent (SCE) product using Advanced Very High Resolution Radiometer (AVHRR) and Moderate Resolution Imaging Spectroradiometer (MODIS) data spanning from 1980's to date. This new product (JAXA/SCE) has higher spatial resolution and smaller commission error compared with traditional SCE dataset of National Oceanic and Atmospheric Administration (NOAA/SCE). Continuity of the algorithm is another strong point in JAXA/SCE. According to the new JAXA/SCE dataset, the Eurasian SCE has been significantly retreating since 1980's, especially in late spring and early summer. Here, we investigate impacts of early summer Eurasian snow cover change on atmospheric circulation in Northern mid-latitudes, especially over the East Asia, using the new JAXA/SCE dataset and a few reanalysis data. We will present analyzed results on relationships between early summer SCE anomaly over the Eurasia and changes in atmospheric circulations such as upper level zonal jets (changes in strength, positions, etc.) over the East Asia.

Three-Dimensional Printing as an Interdisciplinary Communication Tool: Preparing for Removal of a Giant Renal Tumor and Atrium Neoplastic Mass.

PubMed

Golab, Adam; Slojewski, Marcin; Brykczynski, Miroslaw; Lukowiak, Magdalena; Boehlke, Marek; Matias, Daniel; Smektala, Tomasz

2016-08-22

Three-dimensional (3D) printing involves preparing 3D objects from a digital model. These models can be used to plan and practice surgery. We used 3D printing to plan for a rare complicated surgery involving the removal of a renal tumor and neoplastic mass, which reached the heart atrium. A printed kidney model was an essential element of communication for physicians with different specializations.

Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

DTIC Science & Technology

2016-12-01

Award Number: W81XWH-11-1-0744 TITLE: Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated...Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non- Neoplastic Prostate Tissue 5b. GRANT NUMBER 10623678 5c...Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The goal of this project was to develop molecular models to

Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

DTIC Science & Technology

2015-10-01

with Cancer in Non-Neoplastic Prostate Tissue PRINCIPAL INVESTIGATOR: Farhad Kosari, Ph.D. CONTRACTING ORGANIZATION: Mayo Clinic Rochester, MN...E-Mail: kosari.farhad@mayo.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Mayo Clinic Rochester, MN 55905-0002 8...with the Tissue Request Acquisition Group (TRAG) at the Mayo Clinic , a process was implemented for the collection of resected prostates from

Perceived Social Support Change in Patients with Early-stage Breast Cancer and Controls

PubMed Central

Thompson, Tess; Rodebaugh, Thomas L.; Pérez, Maria; Schootman, Mario; Jeffe, Donna B.

2014-01-01

Objective To identify variables associated with levels of and change in social support in a cohort of early-stage breast cancer patients and age-matched controls. Methods Telephone interviews measuring perceived social support and other demographic and psychosocial variables were conducted at 4–6 weeks and 6, 12, and 24 months after surgery (patients) or a normal/benign screening mammogram (controls). A latent trajectory model was used to model the intercept (starting point) and slope (changing) aspects of social support. Results Participants included 542 controls and 541 patients (77% White, 23% African American; mean age 57.7 [SD = 10.6]). Most participants reported high social support. Patients reported significantly higher levels of social support at baseline than controls. For patients, social support had a significant negative slope that significantly varied between individuals; the intercept of social support also varied significantly. Predictors of lower social support intercept in patients included not being married/partnered, being White, having lower perceived general health, and having higher negative affect (modeled as a latent variable defined by anxiety and depression symptom severity). Patients who were African American (vs. White) or had mastectomy (vs. lumpectomy) had steeper social support declines, and participants with both these characteristics had lower starting points as well as steeper declines. Social support among controls did not change significantly. Conclusions Clinicians might consider psychosocial interventions for patients reporting low social support around the time of diagnosis and surgical treatment, and for patients at risk for steeper declines in support, such as African Americans and women undergoing mastectomy. PMID:23477582

Central nervous system complications after liver transplantation.

PubMed

Kim, Jeong-Min; Jung, Keun-Hwa; Lee, Soon-Tae; Chu, Kon; Roh, Jae-Kyu

2015-08-01

We investigated the diversity of central nervous system complications after liver transplantation in terms of clinical manifestations and temporal course. Liver transplantation is a lifesaving option for end stage liver disease patients but post-transplantation neurologic complications can hamper recovery. Between 1 January 2001 and 31 December 2010, patients who had undergone liver transplantation at a single tertiary university hospital were included. We reviewed their medical records and brain imaging data and classified central nervous system complications into four categories including vascular, metabolic, infectious and neoplastic. The onset of central nervous system complications was grouped into five post-transplantation intervals including acute (within 1 month), early subacute (1-3 months), late subacute (3-12 months), chronic (1-3 years), and long-term (after 3 years). During follow-up, 65 of 791 patients (8.2%) experienced central nervous system complications, with 30 occurring within 1 month after transplantation. Vascular etiology was the most common (27 patients; 41.5%), followed by metabolic (23; 35.4%), infectious (nine patients; 13.8%), and neoplastic (six patients). Metabolic encephalopathy with altered consciousness was the most common etiology during the acute period, followed by vascular disorders. An initial focal neurologic deficit was detected in vascular and neoplastic complications, whereas metabolic and infectious etiologies presented with non-focal symptoms. Our study shows that the etiology of central nervous system complications after liver transplantation changes over time, and initial symptoms can help to predict etiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early motor learning changes in upper-limb dynamics and shoulder complex loading during handrim wheelchair propulsion.

PubMed

Vegter, Riemer J K; Hartog, Johanneke; de Groot, Sonja; Lamoth, Claudine J; Bekker, Michel J; van der Scheer, Jan W; van der Woude, Lucas H V; Veeger, Dirkjan H E J

2015-03-10

To propel in an energy-efficient manner, handrim wheelchair users must learn to control the bimanually applied forces onto the rims, preserving both speed and direction of locomotion. Previous studies have found an increase in mechanical efficiency due to motor learning associated with changes in propulsion technique, but it is unclear in what way the propulsion technique impacts the load on the shoulder complex. The purpose of this study was to evaluate mechanical efficiency, propulsion technique and load on the shoulder complex during the initial stage of motor learning. 15 naive able-bodied participants received 12-minutes uninstructed wheelchair practice on a motor driven treadmill, consisting of three 4-minute blocks separated by two minutes rest. Practice was performed at a fixed belt speed (v = 1.1 m/s) and constant low-intensity power output (0.2 W/kg). Energy consumption, kinematics and kinetics of propulsion technique were continuously measured. The Delft Shoulder Model was used to calculate net joint moments, muscle activity and glenohumeral reaction force. With practice mechanical efficiency increased and propulsion technique changed, reflected by a reduced push frequency and increased work per push, performed over a larger contact angle, with more tangentially applied force and reduced power losses before and after each push. Contrary to our expectations, the above mentioned propulsion technique changes were found together with an increased load on the shoulder complex reflected by higher net moments, a higher total muscle power and higher peak and mean glenohumeral reaction forces. It appears that the early stages of motor learning in handrim wheelchair propulsion are indeed associated with improved technique and efficiency due to optimization of the kinematics and dynamics of the upper extremity. This process goes at the cost of an increased muscular effort and mechanical loading of the shoulder complex. This seems to be associated with an

Executive Function in Early Childhood: Longitudinal Measurement Invariance and Developmental Change

ERIC Educational Resources Information Center

Willoughby, Michael T.; Wirth, R. J.; Blair, Clancy B.

2012-01-01

This study tested the longitudinal measurement invariance and developmental changes of a newly developed battery of executive function (EF) tasks for use in early childhood. The battery was administered in the Family Life Project--a prospective longitudinal study (N = 1,292) of families who were oversampled from low-income and African American…

Maturity-associated variation in change of direction and dribbling speed in early pubertal years and 5-year developmental changes in young soccer players.

PubMed

Valente-Dos-Santos, J; Coelho-E-Silva, M J; Vaz, V; Figueiredo, A J; Capranica, L; Sherar, L B; Elferink-Gemser, M T; Malina, R M

2014-06-01

The purpose of the current study was to assess the developmental changes in change of direction and dribbling speed in youth soccer players taking into account skeletal age (SA), maturity status, body size, estimated fat mass, aerobic endurance, lower limb explosive strength and annual volume of training. Eighty-three male soccer players aged 10-15 years (SA) at baseline were annually followed over 5 years, resulting in an average 4.4 observations per player. After testing for multicollinearity, multi-level regression modeling was used to examine the longitudinal developmental changes on change of direction and dribbling speed. Maturity-associated variability was significant in change of direction and also dribbling speed among young soccer players aged 12-14 years with better scores being performed by late maturers. Moreover, the predicted longitudinal scores for change of direction and dribbling speed improved with SA (P<0.01), SA2 (P<0.01) and skeletal maturity status entered as an additional developmental predictor (P<0.05). Estimated fat-free mass (P<0.01), aerobic endurance (P<0.01) and lower limb strength (P<0.01) were additional predictors in both models. The soccer-specific skill, dibbling speed, was also explained by annual volume of training (P<0.05). Skeletal maturity status explains inter-individual variability on maximal short-term run performances with and without the ball possession at early ages of participation in competitive soccer. The effects tend to persist across ages combined with longitudinal changes in body composition and functional fitness. In the particular case of the ball test, annual volume of training was also a longitudinal performance predictor.

Organizational change, psychosocial work environment, and non-disability early retirement: a prospective study among senior public employees.

PubMed

Breinegaard, Nina; Jensen, Johan Høy; Bonde, Jens Peter

2017-05-01

Objective This study examines the impact of organizational change and psychosocial work environment on non-disability early retirement among senior public service employees. Methods In January and February 2011, Danish senior public service employees aged 58-64 years (N=3254) from the Capital Region of Denmark responded to a survey assessing psychosocial work environment (ie, social capital, organizational justice, and quality of management). Work-unit organizational changes (ie, change of management, merging, demerging, and relocation) were recorded from January 2009 to March 2011. Weekly data on non-disability early retirement transfer were obtained from the DREAM register database, which holds weekly information about all public benefit payments in Denmark. Hazard ratios (HR) for early retirement following employees' 60 th birthday were estimated with Cox regression adjusted for age, gender, and socioeconomic status. Results Exposure to change of management [HR 1.37, 95% confidence interval (95% CI) 1.13-1.66], mergers (HR 1.23, 95% CI 1.02-1.48), and relocation of work unit (HR 1.24, 95% CI 1.01-1.54) increased rate of non-disability early retirement, while demerging of work unit did not (HR 1.03, 95% CI 0.79-1.33). Work units with lower levels of social capital (HR 1.22, 95% CI 1.05-1.41), organizational justice, (HR 1.18, 95% CI 1.04-1.32), and quality of management (HR 1.14, 95% CI 1.02-1.25) increased rate of early retirement. Conclusion Organizational change and poor psychosocial work environment contribute to non-disability early retirement among senior public service employees, measured at work-unit level.

Reductions in Radiographic Progression in Early Rheumatoid Arthritis Over Twenty-Five Years: Changing Contribution From Rheumatoid Factor in Two Multicenter UK Inception Cohorts.

PubMed

Carpenter, Lewis; Norton, Sam; Nikiphorou, Elena; Jayakumar, Keeranur; McWilliams, Daniel F; Rennie, Kirsten L; Dixey, Josh; Kiely, Patrick; Walsh, David Andrew; Young, Adam

2017-12-01

To assess the 5-year progression of erosions and joint space narrowing (JSN) and their associations with rheumatoid factor (RF) status in 2 large, multicenter, early rheumatoid arthritis cohorts, spanning 25 years. Radiographic joint damage was recorded using the Sharp/van der Heijde (SHS) method in the Early Rheumatoid Arthritis Study (ERAS), 1986-2001, and the Early Rheumatoid Arthritis Network (ERAN), 2002-2013. Mixed-effects negative binomial regression estimated changes in radiographic damage over 5 years, including erosions and JSN, separately. RF, along with age, sex, and baseline markers of disease activity were controlled for. A total of 1,216 patients from ERAS and 446 from ERAN had radiographic data. Compared to ERAS, ERAN patients had a lower mean total SHS score at baseline (ERAN 6.2 versus ERAS 10.5; P < 0.001) and mean annual rate of change (ERAN 2.5 per year versus ERAS 6.9 per year; P < 0.001). Seventy-four percent of ERAS and 27% of ERAN patients progressed ≥5 units. Lower scores at baseline in ERAN were largely driven by reductions in JSN (ERAS 3.9 versus ERAN 1.2; P < 0.001), along with erosions (ERAS 1.9 versus ERAN 0.8; P < 0.001). RF was associated with greater progression in each cohort, but the absolute difference in mean annual rate of change for RF-positive patients was substantially higher for ERAS (RF positive 8.6 versus RF negative 5.1; P < 0.001), relative to ERAN (RF positive 2.0 versus RF negative 1.9; P = 0.855). Radiographic progression was shown to be significantly reduced between the 2 cohorts, and was associated with lower baseline damage and other factors, including changes in early disease-modifying antirheumatic drug use. The impact of RF status as a prognostic marker of clinically meaningful change in radiographic progression has markedly diminished in the context of more modern treatment. © 2017, American College of Rheumatology.

Sea-level change and demography during the last glacial termination and early Holocene across the Australian continent

NASA Astrophysics Data System (ADS)

Williams, Alan N.; Ulm, Sean; Sapienza, Tom; Lewis, Stephen; Turney, Chris S. M.

2018-02-01

Future changes in sea-level are projected to have significant environmental and social impacts, but we have limited understanding of comparable rates of change in the past. Using comprehensive palaeoenvironmental and archaeological datasets, we report the first quantitative model of the timing, spatial extent and pace of sea-level change in the Sahul region between 35-8 ka, and explore its effects on hunter-gatherer populations. Results show that the continental landmass (excluding New Guinea) increased to 9.80 million km2 during the Last Glacial Maximum (LGM), before a reduction of 2.12 million km2 (or ∼21.6%) to the early Holocene (8 ka). Almost 90% of this inundation occurs during and immediately following Meltwater Pulse (MWP) 1a between 14.6 and 8 ka. The location of coastlines changed on average by 139 km between the LGM and early Holocene, with some areas >300 km, and at a rate of up to 23.7 m per year (∼0.6 km land lost every 25-year generation). Spatially, inundation was highly variable, with greatest impacts across the northern half of Australia, while large parts of the east, south and west coastal margins were relatively unaffected. Hunter-gatherer populations remained low throughout (<30,000), but following MWP1a, increasing archaeological use of the landscape, comparable to a four-fold increase in populations, and indicative of large-scale migration away from inundated regions (notably the Bass Strait) are evident. Increasing population density resulting from MWP1a (from 1/655 km2 to 1/71 km2) may be implicated in the development of large and complex societies later in the Holocene. Our data support the hypothesis that late Pleistocene coastal populations were low, with use of coastal resources embedded in broad-ranging foraging strategies, and which would have been severely disrupted in some regions and at some time periods by sea-level change outpacing tolerances of mangals and other near-shore ecological communities.

Acoustic changes in student actors' voices after 12 months of training.

PubMed

Walzak, Peta; McCabe, Patricia; Madill, Cate; Sheard, Christine

2008-05-01

This study was to evaluate acoustic changes in student actors' voices after 12 months of actor training. The design used was a longitudinal study. Eighteen students enrolled in an Australian tertiary 3-year acting program (nine male and nine female) were assessed at the beginning of their acting course and again 12 months later using a questionnaire, interview, maximum phonation time (MPT), reading, spontaneous speaking, sustained phonation tasks, and a pitch range task. Samples were analyzed for MPT, fundamental frequency across tasks, pitch range for speaking and reading, singing pitch range, noise-to-harmonic ratio, shimmer, and jitter. After training, measures of shimmer significantly increased for both male and female participants. Female participants' pitch range significantly increased after training, with a significantly lower mean frequency for their lowest pitch. The finding of limited or negative changes for some measures indicate that further investigation is required into the long-term effects of actor voice training and which parameters of voicing are most targeted and valued in training. Particular investigation into the relationship between training targets and outcomes could more reliably inform acting programs about changes in teaching methodologies. Further research into the relationship between specific training techniques, physiological changes, and vocal changes may also provide information on implementing more evidence-based training methods.

Early changes of procalcitonin may advise about prognosis and appropriateness of antimicrobial therapy in sepsis.

PubMed

Georgopoulou, Antonia-Panagiota; Savva, Athina; Giamarellos-Bourboulis, Evangelos J; Georgitsi, Marianna; Raftogiannis, Maria; Antonakos, Nicolaos; Apostolidou, Efterpi; Carrer, Dionyssia-Pinelopi; Dimopoulos, George; Economou, Aggelos; Efthymiou, George; Galanakis, Nearchos; Galani, Labrini; Gargalianos, Panagiotis; Karaiskos, Ilias; Katsenos, Chrisostomos; Kavatha, Dimitra; Koratzanis, Evangelos; Labropoulos, Panagiotis; Lada, Malvina; Nakos, George; Paggalou, Evgenia; Panoutsopoulos, George; Paraschos, Michael; Pavleas, Ioannis; Pontikis, Konstantinos; Poulakou, Garyfallia; Prekates, Athanassios; Sybardi, Styliani; Theodorakopoulou, Maria; Trakatelli, Christina; Tsiaoussis, Panagiotis; Gogos, Charalambos; Giamarellou, Helen; Armaganidis, Apostolos; Meisner, Michael

2011-06-01

The objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis. A prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%. Death occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003). Changes of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials. Copyright © 2011 Elsevier Inc. All rights reserved.

Climate Change in Lowland Central America During the Late Deglacial and Early Holocene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hillesheim, M B; Hodell, D A; Leyden, B W

2005-02-08

The transition from arid glacial to moist early Holocene conditions represented a profound change in northern lowland Neotropical climate. Here we report a detailed record of changes in moisture availability during the latter part of this transition ({approx}11,250 to 7,500 cal yr BP) inferred from sediment cores retrieved in Lake Peten Itza, northern Guatemala. Pollen assemblages demonstrate that a mesic forest had been largely established by {approx}11,250 cal yr BP, but sediment properties indicate that lake level was more than 35 m below modern stage. From 11,250 to 10,350 cal yr BP, during the Preboreal period, lithologic changes in sedimentsmore » from deep-water cores (>50 m below modern water level) indicate several wet-dry cycles that suggest distinct changes in effective moisture. Four dry events (designated PBE1-4) occurred at 11,200, 10,900, 10,700, and 10,400 cal yr BP and correlate with similar variability observed in the Cariaco Basin titanium record and glacial meltwater pulses into the Gulf of Mexico. After 10,350 cal yr BP, multiple sediment proxies suggest a shift to a more persistently moist early Holocene climate. Comparison of results from Lake Peten Itza with other records from the circum-Caribbean demonstrates a coherent climate response during the entire span of our record. Furthermore, lowland Neotropical climate during the late deglacial and early Holocene period appears to be tightly linked to climate change in the high-latitude North Atlantic. We speculate that the observed changes in lowland Neotropical precipitation were related to the intensity of the annual cycle and associated displacements in the mean latitudinal position of the Intertropical Convergence Zone and Azores-Bermuda high-pressure system. This mechanism operated on millennial-to-submillennial timescales and may have responded to changes in solar radiation, glacial meltwater, North Atlantic sea ice, and the Atlantic meridional overturning circulation (MOC).« less

Changes in spontaneous brain activity in early Parkinson's disease.

PubMed

Yang, Hong; Zhou, Xiaohong Joe; Zhang, Min-Ming; Zheng, Xu-Ning; Zhao, Yi-Lei; Wang, Jue

2013-08-09

Resting state brain activity can provide valuable insights into the pathophysiology of Parkinson's disease (PD). The purpose of the present study was (a) to investigate abnormal spontaneous neuronal activity in early PD patients using resting-state functional MRI (fMRI) with a regional homogeneity (ReHo) method and (b) to demonstrate the potential of using changes in abnormal spontaneous neuronal activity for monitoring the progression of PD during its early stages. Seventeen early PD patients were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr disability scale and the Mini-mental State Examination (MMSE) were compared with seventeen gender- and age-matched healthy controls. All subjects underwent MRI scans using a 1.5T General Electric Signa Excite II scanner. The MRI scan protocol included whole-brain volumetric imaging using a 3D inversion recovery prepared (IR-Prep) fast spoiled gradient-echo pulse sequence and 2D multi-slice (22 axial slices covering the whole brain) resting-state fMRI using an echo planar imaging (EPI) sequence. Images were analyzed in SPM5 together with a ReHo algorithm using the in-house software program REST. A corrected threshold of p<0.05 was determined by AlphaSim and used in statistical analysis. Compared with the healthy controls, the early PD group showed significantly increased ReHo in a number of brain regions, including the left cerebellum, left parietal lobe, right middle temporal lobe, right sub-thalamic nucleus areas, right superior frontal gyrus, middle frontal gyrus (MFG), right inferior parietal lobe (IPL), right precuneus lobe, left MFG and left IPL. Additionally, significantly reduced ReHo was also observed in the early PD patients in the following brain regions: the left putamen, left inferior frontal gyrus, right hippocampus, right anterior cingulum, and bilateral lingual gyrus. Moreover, in PD patients, ReHo in the left putamen was negatively correlated with the UPDRS scores (r=-0

Adolescents’ Changing Future Expectations Predict the Timing of Adult Role Transitions

PubMed Central

Beal, Sarah J.; Crockett, Lisa J.; Peugh, James

2016-01-01

Individual differences in the transition to adulthood are well established. This study examines the extent to which heterogeneity in pathways to adulthood that have been observed in the broader U.S. population are mirrored in adolescents’ expectations regarding when they will experience key adult role transitions (e.g., marriage). Patterns of change in adolescents’ expectations and the relations between their expectations and subsequent role transitions are also explored. Data from 626 youth in Grade 11 (M age = 16), Grade 12, and early adulthood (M age = 23) are analyzed using mover-stayer latent transition analysis. Results indicate three profiles of expected timing, corresponding to youth who anticipate early role entry (i.e., early starters), youth who anticipate earlier entry into employment but no other roles (i.e., employment-focused), and youth who anticipate delays in role transitions favoring increased education (i.e., education-focused). Two-thirds of youths changed their expectations from Grade 11 to 12. Grade 11 and 12 profile membership predicted role transitions in early adulthood. These findings highlight the importance of adolescents’ expectations and changes in expectations across time in shaping entry into adulthood. PMID:27548390

Early changes of parotid density and volume predict modifications at the end of therapy and intensity of acute xerostomia.

PubMed

Belli, Maria Luisa; Scalco, Elisa; Sanguineti, Giuseppe; Fiorino, Claudio; Broggi, Sara; Dinapoli, Nicola; Ricchetti, Francesco; Valentini, Vincenzo; Rizzo, Giovanna; Cattaneo, Giovanni Mauro

2014-10-01

To quantitatively assess the predictive power of early variations of parotid gland volume and density on final changes at the end of therapy and, possibly, on acute xerostomia during IMRT for head-neck cancer. Data of 92 parotids (46 patients) were available. Kinetics of the changes during treatment were described by the daily rate of density (rΔρ) and volume (rΔvol) variation based on weekly diagnostic kVCT images. Correlation between early and final changes was investigated as well as the correlation with prospective toxicity data (CTCAEv3.0) collected weekly during treatment for 24/46 patients. A higher rΔρ was observed during the first compared to last week of treatment (-0,50 vs -0,05HU, p-value = 0.0001). Based on early variations, a good estimation of the final changes may be obtained (Δρ: AUC = 0.82, p = 0.0001; Δvol: AUC = 0.77, p = 0.0001). Both early rΔρ and rΔvol predict a higher "mean" acute xerostomia score (≥ median value, 1.57; p-value = 0.01). Median early density rate changes for patients with mean xerostomia score ≥ / < 1.57 were -0.98 vs -0.22 HU/day respectively (p = 0.05). Early density and volume variations accurately predict final changes of parotid glands. A higher longitudinally assessed score of acute xerostomia is well predicted by higher rΔρ and rΔvol in the first two weeks of treatment: best cut-off values were -0.50 HU/day and -380 mm(3)/day for rΔρ and rΔvol respectively. Further studies are necessary to definitively assess the potential of early density/volume changes in identifying more sensitive patients at higher risk of experiencing xerostomia.

Changes in the DNA methylation profile of the rat H19 gene upstream region during development and transgenic hepatocarcinogenesis and its role in the imprinted transcriptional regulation of the H19 gene.

PubMed

Manoharan, Herbert; Babcock, Karlee; Pitot, Henry C

2004-09-01

Monoallelic expression of the imprinted H19 and insulin-like growth factor-2 (Igf2) genes depends on the hypomethylation of the maternal allele and hypermethylation of the paternal allele of the H19 upstream region. Previous studies from our laboratory on liver carcinogenesis in the F1 hybrid of Fischer 344 (F344) and Sprague-Dawley Alb SV40 T Ag transgenic rat (SD) strains revealed the biallelic expression of H19 in hepatomas. We undertook a comparative study of the DNA methylation status of the upstream region of H19 in fetal, adult, and neoplastic liver. Bisulfite DNA sequencing analysis of a 3.745-kb DNA segment extending from 2950 to 6695 bp of the H19 upstream region revealed marked variations in the methylation patterns in fetal, adult, and neoplastic liver. In the fetal liver, equal proportions of hyper- and hypomethylated strands revealed the differentially methylated status of the parental alleles, but in neoplastic liver a pronounced change in the pattern of methylation was observed with a distinct change to hypomethylation in the short segments between 2984 and 3301 bp, 6033-6123 bp, and 6518-6548 bp. These results indicated that methylation of all cytosines in this region may contribute to the imprinting status of the rat H19 gene. This phenomenon of differential methylation-related epigenetic alteration in the key cis-regulatory domains of the H19 promoter influences switching to biallelic expression in hepatocellular carcinogenesis. Similar to mouse and human, we showed that the zinc-finger CCTCC binding factor (CTCF) binds to the unmethylated CTCF binding site in the upstream region to influence monoallelic imprinted expression in fetal liver. CTCF does not appear to be rate limiting in fetal, normal, and neoplastic liver. 3' to the CTCF binding sites, another DNA region exhibits methylation of CpG's in both DNA strands in adult liver, retention of the imprint in fetal liver, and complete demethylation in neoplastic liver. In this region is also a

Early Childhood Development Policy and Programming in India: Critical Issues and Directions for Paradigm Change

ERIC Educational Resources Information Center

Sharma, Adarsh; Sen, Rekha Sharma; Gulati, Renu

2008-01-01

The critical importance of the early childhood years and the rights perspective to human development has made policy and programming for early childhood development an imperative for every nation. In India, poverty, changing economic and social structures resulting in the breakdown of traditional coping mechanisms and family care systems, and the…

Sources of Continuity and Change in Activity Level in Early Childhood

ERIC Educational Resources Information Center

Saudino, Kimberly J.

2012-01-01

Actigraphs and parent and observer ratings were used to explore genetic influences on continuity and change in activity level (AL) in early childhood. Over 300 pairs of twins wore actigraphs for a 48-hr period in the home and laboratory at ages 2 and 3. AL was genetically influenced at both ages with little evidence of differential heritability…

Gene Expression in Human Meniscal Tears has Limited Association with Early Degenerative Changes in Knee Articular Cartilage

PubMed Central

Brophy, Robert H.; Sandell, Linda J.; Cheverud, James M.; Rai, Muhammad Farooq

2018-01-01

Purpose/Aim Meniscus tears are a common injury to the knee associated with the development of osteoarthritis. Gene expression in the injured meniscus may be associated with early degeneration in the articular cartilage. The purpose of this study was to test the hypothesis that gene expression in meniscus tears is associated with early degenerative changes in the articular cartilage at the time of partial meniscectomy. Materials and Methods Torn meniscus was removed at the time of partial meniscectomy in 63 patients without radiographic osteoarthritis. Meniscal mRNA expression was measured by quantitative PCR for multiple molecular markers of osteoarthritis and cartilage homeostasis. The presence of early degenerative changes in the knee was recorded by X-ray (N=63), magnetic resonance imaging (MRI, N=48) and arthroscopy (N=63). Gene expression was tested for correlation with the presence/absence of degenerative changes after adjusting for age, sex and body mass index. Results Overall gene expression varied significantly with degenerative changes based on X-ray (P=0.047) and MRI (P=0.018). The linear combination of gene variation was also significant. However, only adiponectin (ADIPOQ) (P=0.015) was expressed at a significantly lower level in patients with chondrosis on MRI while the expression of ADIPOQ (P=0.035) and resistin (RETN) (P=0.017) was higher in patients with early degenerative changes on X-ray. Conclusions There is an overall association of gene expression in meniscal tears to early degenerative changes in the knee, but only a limited number of specific genes demonstrate this relationship. The roles of adiponectin and resistin in knee injury and osteoarthritis deserve further study. PMID:27435997

[Early detection of cervical cancer in Chile: time for change].

PubMed

Léniz Martelli, Javiera; Van De Wyngard, Vanessa; Lagos, Marcela; Barriga, María Isabel; Puschel Illanes, Klaus; Ferreccio Readi, Catterina

2014-08-01

Mortality rates for cervical cancer (CC) in Chile are higher than those of developed countries and it has an unequal socioeconomic distribution. The recognition of human papilloma virus (HPV) as the causal agent of cervical cancer in the early 80's changed the prevention paradigms. Current goals are to prevent HPV infection by vaccination before the onset of sexual activity and to detect HPV infection in women older than 30 years. This article reviews CC prevention and early detection methods, discusses relevant evidence to support a change in Chile and presents an innovation proposal. A strategy of primary screening based on HPV detection followed by triage of HPV-positive women by colposcopy in primary care or by cytological or molecular reflex testing is proposed. Due to the existence in Chile of a well-organized nationwide CC prevention program, the replacement of a low-sensitivity screening test such as the Papanicolau test with a highly sensitive one such as HPV detection, could quickly improve the effectiveness of the program. The program also has a network of personnel qualified to conduct naked-eye inspections of the cervix, who could easily be trained to perform triage colposcopy. The incorporation of new prevention strategies could reduce the deaths of Chilean women and correct inequities.

Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy

PubMed Central

Rodríguez-Peña, Ana B.; Fuentes-Calvo, Isabel; Docherty, Neil G.; Arévalo, Miguel; Grande, María T.; Eleno, Nélida; Pérez-Barriocanal, Fernando; López-Novoa, José M.

2014-01-01

Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis. PMID:25101263

Effect of angiotensin II and small GTPase Ras signaling pathway inhibition on early renal changes in a murine model of obstructive nephropathy.

PubMed

Rodríguez-Peña, Ana B; Fuentes-Calvo, Isabel; Docherty, Neil G; Arévalo, Miguel; Grande, María T; Eleno, Nélida; Pérez-Barriocanal, Fernando; López-Novoa, José M

2014-01-01

Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis.

Changes in K-12 Education: Implications for the BC Post-Secondary System

ERIC Educational Resources Information Center

McQuarrie, Fiona A. E.

2016-01-01

It is generally assumed by educators that the K-12 curriculum--the curriculum used in primary, elementary, and secondary education--will affect students' post-secondary educational experiences and their ability to enter the workforce. This report takes a multi-faceted approach to addressing the impact of changes in the K-12 curriculum on students'…

High-throughput immunohistochemical profiling of primary brain tumors and non-neoplastic systemic organs with a specific antibody against the mutant isocitrate dehydrogenase 1 R132H protein.

PubMed

Ikota, Hayato; Nobusawa, Sumihito; Tanaka, Yuko; Yokoo, Hideaki; Nakazato, Yoichi

2011-04-01

Isocitrate dehydrogenase 1 (IDH1) mutations are common in grade II-III diffuse gliomas and secondary glioblastomas. The aim of this study is to investigate the staining pattern of mIDH1R132H, an antibody specific to mutant IDH1 protein, in primary brain tumors and non-neoplastic systemic organs. Eight of 13 diffuse astrocytomas, 1 of 6 anaplastic astrocytomas, 9 of 11 oligodendrogliomas, 15 of 22 anaplastic oligodendrogliomas, 6 of 7 oligoastrocytomas, and 5 of 8 anaplastic oligoastrocytomas showed both cytoplasmic and nuclear positivity. Two of 25 atypical meningiomas and 2 of 42 pituitary adenomas were positive for mIDH1R132H. The following non-neoplastic systemic organs showed positivity in the cytoplasm alone: the myocardium, peribronchial glands, interlobular ducts of the salivary gland, gastric fundic gland, columnar epithelia of the large bowel, hepatocytes, centroacinar cells, the intercalated ducts of the pancreas, renal proximal and distal tubules, adrenocortex, ovarian granulosa cells, and the choroid plexus epithelia. It was concluded that the immunopositivity detected in non-neoplastic systemic organs was due to cross-reactivity, because immunohistochemistry with an anti-mitochondrial antibody revealed that the mIDH1R132H staining pattern was identical to that of the mitochondria. Therefore, mIDH1R132H positivity should only be considered to be validated when a cell shows both cytoplasmic and nuclear staining.

Interpersonal Development, Stability, and Change in Early Adulthood

PubMed Central

Wright, Aidan G. C.; Pincus, Aaron L.; Lenzenweger, Mark F.

2011-01-01

Objective This goal of this research was to explore the development of the interpersonal system mapped by the interpersonal circumplex in early adulthood (Ages 18-22). Method This study uses the Longitudinal Study of Personality Disorders sample (N = 250; 53% Female). Participants completed the Revised Interpersonal Adjective Scales (Wiggins, Trapnell, & Phillips, 1988) in their freshman, sophomore, and senior years of college. Estimates of structural, rank-order, mean, individual, and ipsative stability were calculated for the broad interpersonal dimensions of Dominance and Affiliation, and also the lower-order octant scales. Additionally, the interpersonal profile parameters of differentiation and prototypicality were calculated at each wave and explored longitudinally, and also used as predictors of interpersonal stability. Results We found excellent structural and high rank-order and ipsative stability in the interpersonal scales over this time period. Mean increases on the Affiliation axis, but not on the Dominance axis, were found to mask differential rates of change among the octant scales, along with significant individual variation in the rates of change. Interpersonal differentiation and prototypicality were related to higher stability in overall interpersonal style. Conclusions Results point to evidence of both stability and nuanced change, illuminating some of the features of the structural variables that can be derived from interpersonal circumplex profiles. PMID:22224462

Parent and clinician agreement regarding early behavioral signs in 12- and 18-month-old infants at-risk of autism spectrum disorder.

PubMed

Sacrey, Lori-Ann R; Zwaigenbaum, Lonnie; Bryson, Susan; Brian, Jessica; Smith, Isabel M; Roberts, Wendy; Szatmari, Peter; Vaillancourt, Tracy; Roncadin, Caroline; Garon, Nancy

2018-03-01

Parent and clinician agreement regarding early behavioral signs of Autism Spectrum Disorder (ASD) in children from a high-risk cohort (siblings of children diagnosed with ASD, n = 188) was examined. Infants were assessed prospectively at 12 and 18 months of age using the clinician administered Autism Observational Scale for Infants (AOSI) and the Autism Parent Screen for Infants (APSI) and underwent a blind independent diagnostic assessment for ASD at 36 months of age. Direct comparison of parent and clinician ratings showed poor agreement on all early behavioral signs, with parent-reported symptoms being better able to differentiate between children with and without ASD at both 12 and 18 months of age compared to clinician observations during a brief office visit. The results suggest that parents may detect some clinically informative behaviors based on their day-to-day observations more readily than do clinicians during brief clinical assessments, a result that needs to be replicated in a non-sibling cohort. Autism Res 2018, 11: 539-547. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. Parents of children at high-risk of autism spectrum disorder (ASD; have an older sibling with ASD) and clinicians were compared on their reporting of 19 early signs of autism. Direct comparison of parent and clinician ratings showed poor agreement on all early behavioral signs, with parent-reported symptoms being better able to differentiate between children with and without ASD at both 12 and 18 months of age compared to clinician observations during a brief office visit. This suggests that parents may have important information regarding early development of their high-risk child. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Children's Elicitation of Changes in Parenting during the Early Childhood Years

PubMed Central

Ansari, Arya; Crosnoe, Robert

2015-01-01

Using a subsample of the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B; n = 1,550), this study identified parents who engaged in more developmentally problematic parenting—in the form of low investment, above average television watching, and use of spanking—when their children were very young (M = 24.41 months, SD = 1.23) but changed their parenting in more positive directions over time. Latent profile analysis and other techniques revealed that parents who demonstrated less optimal parenting behaviors when their children were 2 years old were more likely to be African American, from lower socioeconomic backgrounds, and experiencing greater depressive symptoms. Approximately half of such parents, however, made positive changes in their parenting practices, with 5% in the profile characterized by high investment and low use of spanking by the time that their children were in elementary school. These positive changes in parenting behavior were more likely to occur among parents whose children were already demonstrating early reading skills and less problem behavior. These potential “child effects”, suggesting that children elicited improvements in parenting, were more pronounced among higher income families but did not vary according to parents’ educational attainment. Findings from this study have important implications for intervention programs, suggesting that children's academic and behavioral skills can be leveraged as one means of facilitating positive parenting. PMID:26124539

Children's Elicitation of Changes in Parenting during the Early Childhood Years.

PubMed

Ansari, Arya; Crosnoe, Robert

Using a subsample of the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B; n = 1,550), this study identified parents who engaged in more developmentally problematic parenting-in the form of low investment, above average television watching, and use of spanking-when their children were very young ( M = 24.41 months, SD = 1.23) but changed their parenting in more positive directions over time. Latent profile analysis and other techniques revealed that parents who demonstrated less optimal parenting behaviors when their children were 2 years old were more likely to be African American, from lower socioeconomic backgrounds, and experiencing greater depressive symptoms. Approximately half of such parents, however, made positive changes in their parenting practices, with 5% in the profile characterized by high investment and low use of spanking by the time that their children were in elementary school. These positive changes in parenting behavior were more likely to occur among parents whose children were already demonstrating early reading skills and less problem behavior. These potential "child effects", suggesting that children elicited improvements in parenting, were more pronounced among higher income families but did not vary according to parents' educational attainment. Findings from this study have important implications for intervention programs, suggesting that children's academic and behavioral skills can be leveraged as one means of facilitating positive parenting.

Meiotic recombination protein Rec12: functional conservation, crossover homeostasis and early crossover/non-crossover decision

PubMed Central

Kan, Fengling; Davidson, Mari K.; Wahls, Wayne P.

2011-01-01

In fission yeast and other eukaryotes, Rec12 (Spo11) is thought to catalyze the formation of dsDNA breaks (DSBs) that initiate homologous recombination in meiosis. Rec12 is orthologous to the catalytic subunit of topoisomerase VI (Top6A). Guided by the crystal structure of Top6A, we engineered the rec12 locus to encode Rec12 proteins each with a single amino acid substitution in a conserved residue. Of 21 substitutions, 10 significantly reduced or abolished meiotic DSBs, gene conversion, crossover recombination and the faithful segregation of chromosomes. Critical residues map within the metal ion-binding pocket toprim (E179A, D229A, D231A), catalytic region 5Y-CAP (R94A, D95A, Y98F) and the DNA-binding interface (K201A, G202E, R209A, K242A). A subset of substitutions reduced DSBs but maintained crossovers, demonstrating crossover homeostasis. Furthermore, a strong separation of function mutation (R304A) suggests that the crossover/non-crossover decision is established early by a protein–protein interaction surface of Rec12. Fission yeast has multiple crossovers per bivalent, and chromosome segregation was robust above a threshold of about one crossover per bivalent, below which non-disjunction occurred. These results support structural and functional conservation among Rec12/Spo11/Top6A family members for the catalysis of DSBs, and they reveal how Rec12 regulates other features of meiotic chromosome dynamics. PMID:21030440

Changes among Families in Europe and the Future of Early Childhood Education.

ERIC Educational Resources Information Center

Fthenakis, Wassilios E.

Within the European community, demographic changes have been occurring that have particularly affected children. These major transitions, which have direct implications for early childhood care and education, include: (1) increases in life expectancy and reductions in birth rates; (2) a strong overall movement toward individualization of personal…

Stereometric parameters change vs. Topographic Change Analysis (TCA) agreement in Heidelberg Retina Tomography III (HRT-3) early detection of clinical significant glaucoma progression.

PubMed

Dascalu, A M; Cherecheanu, A P; Stana, D; Voinea, L; Ciuluvica, R; Savlovschi, C; Serban, D

2014-01-01

to investigate the sensitivity and specificity of the stereometric parameters change analysis vs. Topographic Change Analysis in early detection of glaucoma progression. 81 patients with POAG were monitored for 4 years (GAT monthly, SAP at every 6 months, optic disc photographs and HRT3 yearly). The exclusion criteria were other optic disc or retinal pathology; topographic standard deviation (TSD>30; inter-test variation of reference height>25 μm. The criterion for structural progression was the following: at least 20 adjacent super-pixels with a clinically significant decrease in height (>5%). 16 patients of the total 81 presented structural progression on TCA. The most useful stereometric parameters for the early detection of glaucoma progression were the following: Rim Area change (sensitivity 100%, specificity 74.2% for a "cut-off " value of -0.05), C/D Area change (sensitivity 85.7%, specificity 71.5% for a "cut off " value of 0.02), C/D linear change (sensitivity 85.7%, specificity 71.5% for a "cut-off " value of 0.02), Rim Volume change (sensitivity 71.4%, specificity 88.8% for a "cut-off " value of -0.04). RNFL Thickness change (<0) was highly sensitive (82%), but less specific for glaucoma progression (45,2%). Changes of the other stereometric parameters have a limited diagnostic value for the early detection of glaucoma progression. TCA is a valuable tool for the assessment of the structural progression in glaucoma patients and its inter-test variability is low. On long-term, the quantitative analysis according to stereometric parameters change is also very important. The most relevant parameters to detect progression are RA, C/D Area, Linear C/D and RV.

Client Attachment Status and Changes in Therapeutic Alliance Early in Treatment.

PubMed

Siefert, Caleb J; Hilsenroth, Mark J

2015-01-01

Several studies have examined associations between client attachment status and therapeutic alliance. Most, however, measure alliance at a single time point only. This study is among the first to examine how client attachment relates to changes in the therapeutic alliance early in treatment. Forty-six outpatients from a university-based community clinic participated. Attachment status was assessed with the Relationship Questionnaire (Bartholomew & Horowitz, 1991) prior to beginning treatment. Participants rated therapeutic alliance after an evaluation feedback session and again early in psychotherapy. Fearful insecurity was associated with declines in therapeutic alliance, while attachment security was associated with increasing client-therapist bonds. Although unrelated to global alliance, preoccupied insecurity was associated with greater confident collaboration at both time points and declines in idealized relationship from the evaluation to the early therapy time point. Results are discussed in light of prior theoretical formulations and previous research. Limitations of the study are reviewed, implications for clinical practice are noted, and suggestions for future research are made. Assessing client attachment status can provide clinicians with information that helps them identify clients at risk for difficulties establishing a therapeutic alliance. Clients high in attachment security are more likely to develop strong bonds with therapists during the early portion of treatment. Clients high in fearful insecurity are at risk for developing weaker alliances early in treatment. Such clients appear more likely to experience declines in client-therapist bond, goal-task agreement and overall alliance early in the treatment process. Clients high in preoccupied insecurity may enter therapy with great confidence in the therapist and willing to engage in therapy but report more conflicts with therapists in the early phase of treatment. Copyright © 2014 John Wiley

Short-term Second Language and Music Training Induces Lasting Functional Brain Changes in Early Childhood

PubMed Central

Moreno, Sylvain; Lee, Yunjo

2014-01-01

Immediate and lasting effects of music or second-language training were examined in early childhood using event-related potentials (ERPs). ERPs were recorded for French vowels and musical notes in a passive oddball paradigm in 36 four- to six-year-old children who received either French or music training. Following training, both groups showed enhanced late discriminative negativity (LDN) in their trained condition (music group–musical notes; French group–French vowels) and reduced LDN in the untrained condition. These changes reflect improved processing of relevant (trained) sounds, and an increased capacity to suppress irrelevant (untrained) sounds. After one year, training-induced brain changes persisted and new hemispheric changes appeared. Such results provide evidence for the lasting benefit of early intervention in young children. PMID:25346534

The Role of Molecular Pathological Epidemiology in the Study of Neoplastic and Non-Neoplastic Diseases in the Era of Precision Medicine

PubMed Central

Ogino, Shuji; Nishihara, Reiko; VanderWeele, Tyler J.; Wang, Molin; Nishi, Akihiro; Lochhead, Paul; Qian, Zhi Rong; Zhang, Xuehong; Wu, Kana; Nan, Hongmei; Yoshida, Kazuki; Milner, Danny A; Chan, Andrew T.; Field, Alison E.; Camargo, Carlos A; Williams, Michelle A; Giovannucci, Edward L.

2016-01-01

Molecular pathology diagnostics to subclassify diseases based on pathogenesis are increasingly common in clinical translational medicine. Molecular pathological epidemiology (MPE) is an integrative transdisciplinary science based on the unique disease principle and the disease continuum theory. While it has been most commonly applied to research on breast, lung, and colorectal cancers, MPE can investigate etiologic heterogeneity in non-neoplastic diseases such as cardiovascular diseases, obesity, diabetes mellitus, drug toxicity, and immunity-related and infectious diseases. This science can enhance causal inference by linking putative etiologic factors to specific molecular biomarkers as outcomes. Technological advances increasingly enable analyses of various -omics, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, microbiome, immunomics, interactomics, etc. Challenges in MPE include sample size limitations (depending on availability of biospecimens or biomedical / radiological imaging), need for rigorous validation of molecular assays and study findings, and paucities of interdisciplinary experts, education programs, international forums, and standardized guidelines. To address these challenges, there are ongoing efforts such as multidisciplinary consortium pooling projects, the International Molecular Pathological Epidemiology (MPE) Meeting Series, and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)-MPE guideline project. Efforts should be made to build biorepository and biobank networks, and worldwide population-based MPE databases. These activities match with the purposes of the Big Data to Knowledge (BD2K), Genetic Associations and Mechanisms in Oncology (GAME-ON), and Precision Medicine Initiatives of the United States National Institute of Health. Given advances in biotechnology, bioinformatics, and computational / systems biology, there are wide open opportunities in MPE to

The neoplastic potential of rat tracheal epithelial cell lines induced by dibenzo(a, i)pyrene and 1-nitropyrene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiang, M.; Ong, T.; Nath, J.

1997-10-01

The rat tracheal epithelial (RTE) cell transformation system is an important short-term assay for respiratory carcinogenesis. In our laboratories, studies have been performed using this assay system to determine the carcinogenic potential of dibenzo(a,i)pyrene (DBP) and 1-nitropyrene (1-NP), two compounds commonly contaminating occupational and environmental settings. RTE cells were exposed in vivo to DBP or 1-NP by intertracheal instillation. RTE cells were then isolated and plated on a medium for determination of cloning and transformation frequencies. Cell lines established from transformed cells induced by DBP and 1-NP were analyzed for their neoplastic potential with the soft agar cloning and themore » athymic nude mouse tumorigenicity assays. Results showed that: (1) incidence of transformed foci in cultures treated with DBP or 1-NP in vivo was significantly higher than that in the control cultures; (2) 8 and 25 cell lines were established from 28 and 48 transformed foci induced by DBP and 1-NP, respectively; (3) 3 of 5 cell lines from DBP and 5 anchorage independent growth in soft agar; (4) some of the cell lines from DBP and 1-NP induced transformed foci formed tumors after cells were injected in athymic nude mice. These results indicate that in vivo exposure to DBP and 1-NP can induce RTE cell transformation and that transformed cells induced by DBP and 1-NP may have neoplastic potential.« less

IQ at Age 12 Following a History of Institutional Care: Findings from the Bucharest Early Intervention Project

ERIC Educational Resources Information Center

Almas, Alisa N.; Degnan, Kathryn A.; Nelson, Charles A.; Zeanah, Charles H.; Fox, Nathan A.

2016-01-01

Young children removed from institutions and placed into foster care or adoptive homes have been shown to experience significant gains in IQ relative to children who remain in institutions. Less is known about the long-term impact of severe early deprivation on development in late childhood. Data are presented from a follow-up of children at 12…

Association between early pregnancy vitamin D status and changes in serum lipid profiles throughout pregnancy.

PubMed

Lepsch, Jaqueline; Eshriqui, Ilana; Farias, Dayana Rodrigues; Vaz, Juliana S; Cunha Figueiredo, Amanda C; Adegboye, Amanda Rodrigues Amorim; Brito, Alex; Mokhtar, Rana; Allen, Lindsay H; Holick, Michael F; Kac, Gilberto

2017-05-01

To evaluate the associations between first trimester 25-hydroxyvitamin D [25(OH)D] status and changes in high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), triglyceride (TG) concentrations, TG/HDL-c, and TC/HDL-c ratios throughout pregnancy. We hypothesized that first trimester 25(OH)D inadequacy is associated with lower concentrations of HDL-c and higher LDL-c, TC, TG, TG/HDL-c, and TC/HDL-c ratios throughout pregnancy. A prospective cohort study with 3 visits at 5-13 (baseline), 20-26, and 30-36 gestational weeks, recruited 194 pregnant women attending a public health care center in Rio de Janeiro, Brazil. Plasma 25(OH)D concentrations were measured in the first trimester using liquid chromatography-tandem mass spectrometry. 25(OH)D concentrations were classified as adequate (≥75nmol/L) or inadequate (<75nmol/L). Serum TC, HDL-c, and TG concentrations were measured enzymatically. Crude and adjusted longitudinal linear mixed-effects models were employed to evaluate the association between the first trimester 25(OH)D status and changes in serum lipid concentrations throughout pregnancy. Confounders adjusted for in the multiple analysis were age, homeostatic model assessment (HOMA), early pregnancy BMI, leisure time physical activity before pregnancy, energy intake, and gestational age. At baseline, 69% of the women had inadequate concentrations of 25(OH)D. Women with 25(OH)D inadequacy had higher mean LDL-c than those with adequate concentrations (91.3 vs. 97.5mg/dL; P=0.064) at baseline. TC, HDL-c, LDL-c TG, TG/HDL-c ratios, and TC/HDL-c ratios, increased throughout pregnancy independently of 25(OH)D concentrations (ANOVA for repeated measures P<0.001). The adjusted models showed direct associations between the first trimester 25(OH)D status and changes in TC (β=9.53; 95%CI=1.12-17.94), LDL-c (β=9.99; 95% CI=3.62-16.36) concentrations, and TC/HDL-c ratios (β=0.16; 95% CI=0.01-0.31) throughout

12 CFR 41.91 - Duties of card issuers regarding changes of address.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 1 2011-01-01 2011-01-01 false Duties of card issuers regarding changes of address. 41.91 Section 41.91 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY FAIR CREDIT REPORTING Identity Theft Red Flags § 41.91 Duties of card issuers regarding changes of...

12 CFR 571.91 - Duties of card issuers regarding changes of address.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 5 2011-01-01 2011-01-01 false Duties of card issuers regarding changes of address. 571.91 Section 571.91 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY FAIR CREDIT REPORTING Identity Theft Red Flags § 571.91 Duties of card issuers regarding changes of...

12 CFR 261b.9 - Changes with respect to publicly announced meeting.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Changes with respect to publicly announced meeting. 261b.9 Section 261b.9 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM RULES REGARDING PUBLIC OBSERVATION OF MEETINGS § 261b.9 Changes with...

Laparoscopic sleeve gastrectomy in patients over 59 years: early recovery and 12-month follow-up.

PubMed

Leivonen, Marja Kaarina; Juuti, Anne; Jaser, Nabil; Mustonen, Harri

2011-08-01

Bariatric surgery has shown to be safe for patients over 60 years with good results especially considering resolving of comorbidities. Sleeve gastrectomy is considered to be safer than gastric bypass (GBP) and more effective than gastric banding with less adverse symptoms. Weight loss may be more modest than after GBP, but the effect on vitamins may also be milder. Since 2007, we collected prospectively 12-month follow-up data from 55 sleeve gastrectomy patients of whom 12 were over 59 years of age. Vitamin and calcium supplements were used postoperatively. The recovery from the operation was recorded during hospital stay, at 1- and 12-month follow-up visits using a standard protocol including laboratory tests. The results between patients over and under 59 years were compared. The preoperative weight and weight loss were comparable between the groups. Operation time was shorter and hospital stay was longer for older patients, p = ns. There was no operative mortality. Early major complications were seen more often in the older age group, 42% vs 9% (p = 0.02), but late complications were more common in younger patients, 17% vs 44%, p = ns. Early complications were mostly bleedings, which did not lengthen the hospital stay, neither were re-operations nor endoscopic procedures needed. Excess weight loss and resolving of comorbidities after 12 months was comparable between the groups. However, vitamin deficiencies and hypoalbuminemia were more common in the older age group, 42% and 23% for vitamins and 44% and 29% for proteins, p = ns. The older patients had more adverse effects related to surgery, 25% vs 9%, and younger had more adverse psychiatric effects, p = ns. Sleeve gastrectomy is effective and safe for older bariatric patients. Weight loss is comparable to younger patients and enough to resolve the comorbidities in most of the patients. With standardized nutritional supplementation, the older patients had more often vitamin deficiencies and

Aging promotes neoplastic disease through effects on the tissue microenvironment.

PubMed

Marongiu, Fabio; Serra, Maria Paola; Doratiotto, Silvia; Sini, Marcella; Fanti, Maura; Cadoni, Erika; Serra, Monica; Laconi, Ezio

2016-12-06

A better understanding of the complex relationship between aging and cancer will provide important tools for the prevention and treatment of neoplasia. In these studies, the hypothesis was tested that aging may fuel carcinogenesis via alterations imposed in the tissue microenvironment. Preneoplastic hepatocytes isolated from liver nodules were orthotopically injected into either young or old syngeneic rats and their fate was followed over time using the dipeptidyl-peptidase type IV (DPPIV) system to track donor-derived-cells. At 3 months post-Tx, the mean size of donor-derived clusters was 11±3 cells in young vs. 42±8 in old recipients. At 8 months post-Tx, no visible lesion were detected in any of 21 young recipients, while 17/18 animals transplanted at old age displayed hepatic nodules, including 7 large tumors. All tumors expressed the DPPIV marker enzyme, indicating that they originated from transplanted cells. Expression of senescence-associated β-galactosidase was common in liver of 18-month old animals, while it was a rare finding in young controls. Finally, both mRNA and IL6 protein were found to be increased in the liver of aged rats compared to young controls. These results are interpreted to indicate that the microenvironment of the aged liver promotes the growth of pre-neoplastic hepatocytes.

California forests show early indications of both range shifts and local persistence under climate change

Treesearch

Josep M. Serra-Diaz; Janet Franklin; Whalen W. Dillon; Alexandra D. Syphard; Frank W. Davis; Ross K. Meentemeyer

2015-01-01

Aim Forest regeneration data provide an early signal of the persistence and migration of tree species, so we investigated whether species shifts due to climate change exhibit a common signal of response or whether changes vary by species. Location California Floristic Province, United...

Pro-inflammatory cytokines and oxidative stress/antioxidant parameters characterize the bio-humoral profile of early cachexia in lung cancer patients.

PubMed

Fortunati, Nicoletta; Manti, Roberta; Birocco, Nadia; Pugliese, Mariateresa; Brignardello, Enrico; Ciuffreda, Libero; Catalano, Maria G; Aragno, Manuela; Boccuzzi, Giuseppe

2007-12-01

Cancer-related cachexia, that is present in about 50% of cancer patients and accounts for 20% of all cancer deaths, is clinically characterized by progressive weight loss, anorexia, metabolic alterations, asthenia, depletion of lipid stores and severe loss of skeletal muscle proteins. The main biochemical and molecular alterations that are responsible for the syndrome are prematurely present in the progress of the disease and the identification of the early stages of cachexia can be useful in targetting patients who will benefit from early treatment. The aim of the present study was to delineate the bio-humoral profile of a group of lung cancer patients either non-cachectic or cachectic by evaluating serum pro-inflammatory cytokines and oxidative stress/antioxidant parameters (both recognized to be involved in cachexia pathogenesis) and pro-inflammatory cytokine gene expression in PBMC (Peripheral blood mononuclear cells) of cancer patients. All serum pro-inflammatory cytokines and oxidative stress/antioxidant parameters significantly increased in neoplastic patients, but only TNF-alpha, ROS, GSH and vitamin E showed a significantly greater increase in cachectic patients. Pro-inflammatory cytokine gene expression mirrored serum level behaviour except for IL-6 that was increased in serum but not as gene expression, suggesting its provenience from tumour tissue. Our data support that the simultaneous determination of ROS, GSH, vitamin E, together with TNF-alpha allows the identification of a lung cancer patient developing cancer-related cachexia. This bio-humoral profile should be used for the early diagnosis and follow-up of the syndrome. Moreover, the evaluation of gene expression in patient PBMC was helpful in differentiating tumour vs host factors, therefore being useful in the study of pathogenetic mechanisms in neoplastic cachectic patients.

Be a CHANGEMASTER: 12 Coaching Strategies for Leading Professional and Personal Change

ERIC Educational Resources Information Center

Reiss, Karla

2012-01-01

"Be a CHANGEMASTER" is a practical guide for school and district leaders that provides 12 strategies for overcoming resistance to change. Unlike more theoretical books, this text shows how to adopt a coaching style of leadership as a systemic change strategy. Numerous examples demonstrate how the strategies used in this book have led to…

How Does Early Feedback in an Online Programming Course Change Problem Solving?

ERIC Educational Resources Information Center

Ebrahimi, Alireza

2012-01-01

How does early feedback change the programming problem solving in an online environment and help students choose correct approaches? This study was conducted in a sample of students learning programming in an online course entitled Introduction to C++ and OOP (Object Oriented Programming) using the ANGEL learning management system platform. My…

Early detection of health and welfare compromises through automated detection of behavioural changes in pigs.

PubMed

Matthews, Stephen G; Miller, Amy L; Clapp, James; Plötz, Thomas; Kyriazakis, Ilias

2016-11-01

Early detection of health and welfare compromises in commercial piggeries is essential for timely intervention to enhance treatment success, reduce impact on welfare, and promote sustainable pig production. Behavioural changes that precede or accompany subclinical and clinical signs may have diagnostic value. Often referred to as sickness behaviour, this encompasses changes in feeding, drinking, and elimination behaviours, social behaviours, and locomotion and posture. Such subtle changes in behaviour are not easy to quantify and require lengthy observation input by staff, which is impractical on a commercial scale. Automated early-warning systems may provide an alternative by objectively measuring behaviour with sensors to automatically monitor and detect behavioural changes. This paper aims to: (1) review the quantifiable changes in behaviours with potential diagnostic value; (2) subsequently identify available sensors for measuring behaviours; and (3) describe the progress towards automating monitoring and detection, which may allow such behavioural changes to be captured, measured, and interpreted and thus lead to automation in commercial, housed piggeries. Multiple sensor modalities are available for automatic measurement and monitoring of behaviour, which require humans to actively identify behavioural changes. This has been demonstrated for the detection of small deviations in diurnal drinking, deviations in feeding behaviour, monitoring coughs and vocalisation, and monitoring thermal comfort, but not social behaviour. However, current progress is in the early stages of developing fully automated detection systems that do not require humans to identify behavioural changes; e.g., through automated alerts sent to mobile phones. Challenges for achieving automation are multifaceted and trade-offs are considered between health, welfare, and costs, between analysis of individuals and groups, and between generic and compromise-specific behaviours. Copyright © 2016

Thoracic corpectomy for neoplastic vertebral bodies using a navigated lateral extracavitary approach-a single-center consecutive case series: technique and analysis.

PubMed

Hartmann, Sebastian; Wipplinger, Christoph; Tschugg, Anja; Kavakebi, Pujan; Örley, Alexander; Girod, Pierre Pascal; Thomé, Claudius

2018-04-01

Thoracic myelopathy is often caused by vertebral body fractures resulting from neoplastic conditions, traumatic events, or infectious diseases. One of the preferred procedures for treating it is the lateral extracavitary approach (LECA) with single-level or multilevel decompressive corpectomy and reconstruction. The aim of this retrospective study was to analyze the thoracic lateral extracavitary approach with corpectomy using vertebral body replacement systems (VBR-S) and dorsal reconstruction. Twenty-four patients with metastatic or primary lesions of thoracic vertebrae T2-T12 underwent spinal decompression and ventral column reconstruction with correction of spinal deformity via a LECA. One-level to four-level corpectomies were performed with additional navigated dorsal pedicle screw fixation at an average of two levels above and below the corpectomy lesion. None of the patients received preoperative spinal embolization, and the majority of the patients were admitted to radiotherapy postoperatively. Their mean age was 56 years (± 15), with a female-to-male sex ratio of 8 to 16. Patients with a minimum follow-up period of 16 months were included. The Karnofsky index, preoperative and postoperative numeric rating scale (NRS), and Frankel scale were measured. In addition, intraoperative loss of blood (LOB), units of packed red blood cell (PRBC) transfusions, the duration of the operation, and the hospitalization period were evaluated and correlated with preoperative and postoperative values. The majority of the patients were suffering from metastatic lesions and were treated with a 1 level corpectomy (median 1 level, range 1 to 4). The mean duration of surgery was 288 min (± 121) and the mean LOB was 1626 mL (± 1486 mL), with approximately two PRBC units per patient used. All patients were transferred to the intensive care unit (ICU) postoperatively, with a mean ICU stay of 2.0 days (± 1 day). The mean hospitalization period was 13 days (± 7�

Does the Brief Observation of Social Communication Change help moving forward in measuring change in early autism intervention studies?

PubMed

Pijl, Mirjam Kj; Rommelse, Nanda Nj; Hendriks, Monica; De Korte, Manon Wp; Buitelaar, Jan K; Oosterling, Iris J

2018-02-01

The field of early autism research is in dire need of outcome measures that adequately reflect subtle changes in core autistic behaviors. This article compares the ability of a newly developed measure, the Brief Observation of Social Communication Change (BOSCC), and the Autism Diagnostic Observation Schedule (ADOS) to detect changes in core symptoms of autism in 44 toddlers. The results provide encouraging evidence for the Brief Observation of Social Communication Change as a candidate outcome measure, as reflected in sufficient inter- and intra-rater reliability, independency from other child characteristics, and sensitivity to capture change. Although the Brief Observation of Social Communication Change did not evidently outperform the Autism Diagnostic Observation Schedule on any of these quality criteria, the instrument may be better able to capture subtle, individual changes in core autistic symptoms. The promising findings warrant further study of this new instrument.

Dental caries and fluorosis experience of 8-12-year-old children by early-life exposure to fluoride.

PubMed

Do, Loc G; Miller, Jenifer; Phelan, Claire; Sivaneswaran, Shanti; Spencer, A John; Wright, Clive

2014-12-01

It is important to evaluate concurrently the benefit for dental caries and the risk for dental fluorosis from early exposure to fluoride among children. To evaluate associations of different levels of exposure to fluoride in early childhood with dental caries and dental fluorosis experience in school children. A Child Dental Health Survey (CDHS) was conducted among school children in the Australian state of New South Wales (NSW) in 2007. Trained and calibrated examination teams conducted oral epidemiologic examinations to assess caries experience as decayed, missing or filled tooth surfaces of the primary and permanent dentitions (dmfs/DMFS) and fluorosis using the Thylstrup & Fejerskov (TF) index on the maxillary central incisors only. A parental questionnaire collected information on residential histories and tap water usage to enable calculation of percentage of 3-year lifetime exposure to fluoride in water. Use of dietary fluoride supplements was also collected. Dental caries and fluorosis experience were compared among groups by levels of exposure to fluoride from water and fluoride supplements in bivariate and multivariable analysis, controlling for socioeconomic factors. Exposure to different fluoride sources varied in the group of 2611 children aged 8-12 years. Lower household income was significantly associated in both bivariate and multivariable analyses with the greater prevalence and severity of primary tooth caries among 8-10-year-old children and permanent tooth caries among 8-12 year old. Exposure to fluoride in water during the first 3 years of life was associated with both caries and fluorosis experience observed at age 8-12 years. Having higher percentage of 3-year lifetime exposure to fluoride in water was associated with higher prevalence of mostly mild fluorosis, but significantly lower prevalence and severity of caries in the primary and permanent dentitions. There were significant associations of dental caries and fluorosis experience with

Early Childhoods in a Changing World

ERIC Educational Resources Information Center

Clark, Margaret M., Ed.; Tucker, Stanley, Ed.

2010-01-01

This book challenges taken for granted views of early childhood across the globe. It deepens and broadens our understanding of what it means to be a child today and of the challenges children face in different parts of the world. It will be essential reading for all who work with young children or are students of early years education and…

Dietary change among hominins and cercopithecids in Ethiopia during the early Pliocene

NASA Astrophysics Data System (ADS)

Levin, Naomi E.; Haile-Selassie, Yohannes; Frost, Stephen R.; Saylor, Beverly Z.

2015-10-01

The incorporation of C4 resources into hominin diet signifies increased dietary breadth within hominins and divergence from the dietary patterns of other great apes. Morphological evidence indicates that hominin diet became increasingly diverse by 4.2 million years ago but may not have included large proportions of C4 foods until 800 thousand years later, given the available isotopic evidence. Here we use carbon isotope data from early to mid Pliocene hominin and cercopithecid fossils from Woranso-Mille (central Afar, Ethiopia) to constrain the timing of this dietary change and its ecological context. We show that both hominins and some papionins expanded their diets to include C4 resources as early as 3.76 Ma. Among hominins, this dietary expansion postdates the major dentognathic morphological changes that distinguish Australopithecus from Ardipithecus, but it occurs amid a continuum of adaptations to diets of tougher, harder foods and to committed terrestrial bipedality. In contrast, carbon isotope data from cercopithecids indicate that C4-dominated diets of the earliest members of the Theropithecus oswaldi lineage preceded the dental specialization for grazing but occurred after they were fully terrestrial. The combined data indicate that the inclusion of C4 foods in hominin diet occurred as part of broader ecological changes in African primate communities.

Dietary change among hominins and cercopithecids in Ethiopia during the early Pliocene

PubMed Central

Levin, Naomi E.; Haile-Selassie, Yohannes; Frost, Stephen R.; Saylor, Beverly Z.

2015-01-01

The incorporation of C4 resources into hominin diet signifies increased dietary breadth within hominins and divergence from the dietary patterns of other great apes. Morphological evidence indicates that hominin diet became increasingly diverse by 4.2 million years ago but may not have included large proportions of C4 foods until 800 thousand years later, given the available isotopic evidence. Here we use carbon isotope data from early to mid Pliocene hominin and cercopithecid fossils from Woranso-Mille (central Afar, Ethiopia) to constrain the timing of this dietary change and its ecological context. We show that both hominins and some papionins expanded their diets to include C4 resources as early as 3.76 Ma. Among hominins, this dietary expansion postdates the major dentognathic morphological changes that distinguish Australopithecus from Ardipithecus, but it occurs amid a continuum of adaptations to diets of tougher, harder foods and to committed terrestrial bipedality. In contrast, carbon isotope data from cercopithecids indicate that C4-dominated diets of the earliest members of the Theropithecus oswaldi lineage preceded the dental specialization for grazing but occurred after they were fully terrestrial. The combined data indicate that the inclusion of C4 foods in hominin diet occurred as part of broader ecological changes in African primate communities. PMID:26371308

Chromosome 17q12 variants contribute to risk of early-onset prostate cancer

PubMed Central

Levin, Albert M.; Machiela, Mitchell J.; Zuhlke, Kimberly A.; Ray, Anna M.; Cooney, Kathleen A.; Douglas, Julie A.

2008-01-01

In a recent genome-wide association study by Gudmundsson et al. (2007), two prostate cancer susceptibility loci were identified on chromosome 17q. The first locus, at 17q12, was distinguished by two intronic single nucleotide polymorphisms (SNPs) in the TCF2 gene (rs4430796 and rs7501939). The second locus was in a gene-poor region of 17q24, where the strongest evidence of association was for SNP rs1859962. To determine if these loci were also associated with hereditary prostate cancer, we genotyped them in a family-based association sample of 403 non-Hispanic white families, including 1,015 men with and without prostate cancer. SNPs rs4430796 and rs7501939, which were in strong linkage disequilibrium (r2=0.68), showed the strongest evidence of prostate cancer association. Using a family-based association test, the “A” allele of SNP rs4430796 was over-transmitted to affected men (p=0.006), with an odds ratio of 1.40 (95%CI=1.09–1.81) under an additive genetic model. Notably, rs4430796 was significantly associated with prostate cancer among men diagnosed at an early (<50 years) but not later age (p=0.006 versus p=0.118). Our results confirm the prostate cancer association with SNPs on chromosome 17q12 initially reported by Gudmundsson et al. In addition, our results suggest that the increased risk associated with these SNPs is approximately doubled in individuals predisposed to develop early onset disease. Importantly, these SNPs do not account for a significant portion of our prior prostate cancer linkage evidence on chromosome 17. Thus, there likely exist one or more additional independent prostate cancer susceptibility loci in this region. PMID:18701471

Serum Carbon Isotope Values Change in Adults in Response to Changes in Sugar-Sweetened Beverage Intake12

PubMed Central

Fakhouri, Tala H. I.; Jahren, A. Hope; Appel, Lawrence J.; Chen, Liwei; Alavi, Reza; Anderson, Cheryl A. M.

2014-01-01

Serum carbon isotope values [13C-to-12C serum carbon isotope ratio (δ13C)], which reflect consumption of corn- and cane-based foods, differ between persons consuming high and low amounts of sugar-sweetened beverages (SSBs). In this study, we determined whether serum δ13C changes in response to change in SSB intake during an 18-mo behavioral intervention trial. Data were from a subset of 144 participants from the PREMIER trial, a completed behavioral intervention (Maryland, 1998–2004). SSB intake was assessed using 2 24-h dietary recall interviews. Blinded serum samples were assayed for δ13C by natural abundance stable isotope mass spectroscopy. Multiple linear regression models with generalized estimating equations and robust variance estimation were used. At baseline, mean SSB intake was 13.8 ± 14.2 fl oz/d, and mean δ13C serum value was −19.3 ± 0.6 units per mil (designated ‰). A reduction of 12 oz (355 mL)/d SSB (equivalent to 1 can of soda per day) was associated with 0.17‰ (95% CI: 0.08‰, 0.25‰ P < 0.0001) reduction in serum δ13C values over 18 mo (equivalent to a 1% reduction in δ13C from baseline). After adjusting for potential confounders, a reduction of 12 oz/d SSB (equivalent to 1 can of soda per day), over an 18-mo period, was associated with 0.12‰ (95% CI: 0.01‰, 0.22‰ P = 0.025) reduction in serum δ13C. These findings suggest that serum δ13C can be used as a measure of dietary changes in SSB intake. PMID:24717368

Changing the game: exploring infants' participation in early play routines

PubMed Central

Fantasia, Valentina; Fasulo, Alessandra; Costall, Alan; López, Beatriz

2014-01-01

Play has proved to have a central role in children's development, most notably in rule learning (Piaget, 1965; Sutton-Smith, 1979) and negotiation of roles and goals (Garvey, 1974; Bruner et al., 1976). Yet very little research has been done on early play. The present study focuses on early social games, i.e., vocal-kinetic play routines that mothers use to interact with infants from very early on. We explored 3-month-old infants and their mothers performing a routine game first in the usual way, then in two violated conditions: without gestures and without sound. The aim of the study is to investigate infants' participation and expectations in the game and whether this participation is affected by changes in the multimodal format of the game. Infants' facial expressions, gaze, and body movements were coded to measure levels of engagement and affective state across the three conditions. Results showed a significant decrease in Limbs Movements and expressions of Positive Affect, an increase in Gaze Away and in Stunned Expression when the game structure was violated. These results indicate that the violated game conditions were experienced as less engaging, either because of an unexpected break in the established joint routine, or simply because they were weaker versions of the same game. Overall, our results suggest that structured, multimodal play routines may constitute interactional contexts that only work as integrated units of auditory and motor resources, representing early communicative contexts which prepare the ground for later, more complex multimodal interactions, such as verbal exchanges. PMID:24936192

Knowledge and beliefs concerning early childhood caries from mothers of children ages zero to 12 months.

PubMed

Azevedo, Marina Sousa; Romano, Ana Regina; Dos Santos, Iná da Silva; Cenci, Maximiliano Sergio

2014-01-01

This study's purpose was to assess mothers' knowledge and beliefs about early childhood caries (ECC) etiology and prevention. This cross-sectional study targeted mothers (N=277) of zero- to 12-month-olds visiting 12 public health care centers in Pelotas, Rio Grande do Sul, Brazil. Information on causes of and recommendations to prevent ECC, as well as socioeconomic and demographic variables, was collected. Chi-square, univariate, and multiple logistic regression analyses were performed (P<.05). Sugar intake and lack of oral hygiene were the most frequently mentioned causes of caries. Ninety percent of the mothers were aware of the need to begin tooth-brushing during their children's first year. Mothers who had more children and were in lower socioeconomic positions were more likely to not know the correct age for the first dental visit. Our findings showed that mothers do not know all the factors that can influence caries in their children. None reported the role of micro-organisms and lack of fluoride in the caries etiology. These findings highlight the importance of providing preventive orientation to the mothers regarding early childhood caries. Information on age of first dental visit should be emphasized, especially among mothers with more than one child and low-income families.

Informing climate change adaptation with insights from famine early warning (Invited)

NASA Astrophysics Data System (ADS)

Funk, C. C.; Verdin, J. P.

2010-12-01

Famine early warning systems provide a unique viewpoint for understanding the implications of climate change on food security, identifying the locations and seasons where millions of food insecure people are dependent upon climate-sensitive agricultural systems. The Famine Early Warning Systems Network (FEWS NET) is a decision support system sponsored by the Office of Food for Peace of the U.S. Agency for International Development (USAID), which distributes over two billion dollars of food aid to more than 40 countries each year. FEWS NET identifies the times and places where food aid is required by the most climatically sensitive and consequently food insecure populations of the developing world. As result, FEWS NET has developed its own "climate service", implemented by USGS, NOAA, and NASA, to support its decision making processes. The foundation of this climate service is the monitoring of current growing conditions for early identification of agricultural drought that might impact food security. Since station networks are sparse in the countries monitored, FEWS NET has a tradition (dating back to 1985) of reliance on satellite remote sensing of vegetation and rainfall. In the last ten years, climate forecasts have become an additional tool for food security assessment, extending the early warning perspective to include expected agricultural outcomes for the season ahead. More recently, research has expanded to include detailed analyses of recent observed climate trends, combined with diagnostic ocean-atmosphere studies. These studies are then used to develop interpretations of GCM scenarios and their implications for future patterns of precipitation and temperature, revealing trends towards warmer/drier climate conditions and increases in the relative frequency of drought. In some regions, like Eastern Africa, such changes seem to be already occurring, with an associated increase in food insecurity. Sub-national analyses for Kenya, for example, point to the

SV40 T antigen alone drives karyotype instability that precedes neoplastic transformation of human diploid fibroblasts.

PubMed

Ray, F A; Peabody, D S; Cooper, J L; Cram, L S; Kraemer, P M

1990-01-01

To define the role of SV40 large T antigen in the transformation and immortalization of human cells, we have constructed a plasmid lacking most of the unique coding sequences of small t antigen as well as the SV40 origin of replication. The promoter for T antigen, which lies within the origin of replication, was deleted and replaced by the Rous sarcoma virus promoter. This minimal construct was co-electroporated into normal human fibroblasts of neonatal origin along with a plasmid containing the neomycin resistance gene (neo). Three G418-resistant, T antigen-positive clones were expanded and compared to three T antigen-positive clones that received the pSV3neo plasmid (capable of expressing large and small T proteins and having two origins of replication). Autonomous replication of plasmid DNA was observed in all three clones that received pSV3neo but not in any of the three origin minus clones. Immediately after clonal expansion, several parameters of neoplastic transformation were assayed. Low percentages of cells in T antigen-positive populations were anchorage independent or capable of forming colonies in 1% fetal bovine serum. The T antigen-positive clones generally exhibited an extended lifespan in culture but rarely became immortalized. Large numbers of dead cells were continually generated in all T antigen-positive, pre-crisis populations. Ninety-nine percent of all T antigen-positive cells had numerical or structural chromosome aberrations. Control cells that received the neo gene did not have an extended life span, did not have noticeable numbers of dead cells, and did not exhibit karyotype instability. We suggest that the role of T antigen protein in the transformation process is to generate genetic hypervariability, leading to various consequences including neoplastic transformation and cell death.

REPEATED TREATMENTS WITH DOXORUBICIN CAUSES ELECTROCARDIOGRAM (ECG) CHANGES AND INCREASED VENTRICULAR PREMATURE BEATS IN WISTAR-KYOTO (WKY) RATS

EPA Science Inventory

Doxorubicin (DOX) is a widely used anthracycline anti-neoplastic drug used to treat tumors. However it has been implicated in irreversible cardiac toxicity via the generation of a proxidant semiquinone free radical, which often results in cardiomyopathy and changes in the ECG. Ac...

Family Relationships from Adolescence to Early Adulthood: Changes in the Family System following Firstborns' Leaving Home

ERIC Educational Resources Information Center

Whiteman, Shawn D.; McHale, Susan M.; Crouter, Ann C.

2011-01-01

This study charted the course of parent-child and sibling relationships from early adolescence to early adulthood and examined how these relationships changed following firstborns' departure from their parents' home for the first time. Data were drawn from a 10-year longitudinal study of family relationships. Participants included mothers,…

Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes

PubMed Central

Cullingford, Timothy E; Markou, Thomais; Fuller, Stephen J; Giraldo, Alejandro; Pikkarainen, Sampsa; Zoumpoulidou, Georgia; Alsafi, Ali; Ekere, Collins; Kemp, Timothy J; Dennis, Jayne L; Game, Laurence; Sugden, Peter H; Clerk, Angela

2008-01-01

Background Endothelin-1 stimulates Gq protein-coupled receptors to promote proliferation in dividing cells or hypertrophy in terminally differentiated cardiomyocytes. In cardiomyocytes, endothelin-1 rapidly (within minutes) stimulates protein kinase signaling, including extracellular-signal regulated kinases 1/2 (ERK1/2; though not ERK5), with phenotypic/physiological changes developing from approximately 12 h. Hypertrophy is associated with changes in mRNA/protein expression, presumably consequent to protein kinase signaling, but the connections between early, transient signaling events and developed hypertrophy are unknown. Results Using microarrays, we defined the early transcriptional responses of neonatal rat cardiomyocytes to endothelin-1 over 4 h, differentiating between immediate early gene (IEG) and second phase RNAs with cycloheximide. IEGs exhibited differential temporal and transient regulation, with expression of second phase RNAs within 1 h. Of transcripts upregulated at 30 minutes encoding established proteins, 28 were inhibited >50% by U0126 (which inhibits ERK1/2/5 signaling), with 9 inhibited 25-50%. Expression of only four transcripts was not inhibited. At 1 h, most RNAs (approximately 67%) were equally changed in total and polysomal RNA with approximately 17% of transcripts increased to a greater extent in polysomes. Thus, changes in expression of most protein-coding RNAs should be reflected in protein synthesis. However, approximately 16% of transcripts were essentially excluded from the polysomes, including some protein-coding mRNAs, presumably inefficiently translated. Conclusion The phasic, temporal regulation of early transcriptional responses induced by endothelin-1 in cardiomyocytes indicates that, even in terminally differentiated cells, signals are propagated beyond the primary signaling pathways through transcriptional networks leading to phenotypic changes (that is, hypertrophy). Furthermore, ERK1/2 signaling plays a major role in

Photodetection of early cancer by laser-induced fluorescence of a tumor-selective dye: apparatus design and realization

NASA Astrophysics Data System (ADS)

Wagnieres, Georges A.; Depeursinge, Christian D.; Monnier, Philippe; Savary, Jean-Francois; Cornaz, Piet F.; Chatelain, Andre; van den Bergh, Hubert

1990-07-01

An apparatus is designed and realized to detect "early" cancer at the surface of the hollow organs in the human body by endoscopic means. The tumor is localized by the laser induced fluorescence of a dye (HPD) which concentrates selectively in the neoplastic tissue after intravenous injection. Fluorescence contrast between the tumor and its normal surroundings is enhanced by subtracting the background autofluorescence which occurs in both types of tissue. This is done by means of 2-color digital images manipulation in real-time. Preliminary clinical tests of the apparatus demonstrated the detection of carcinoma in situ in the esophagus.

Radiofrequency Ablation Versus Endoscopic Submucosal Dissection in Treating Large Early Esophageal Squamous Cell Neoplasia

PubMed Central

Wang, Wen-Lun; Chang, I-Wei; Chen, Chien-Chuan; Chang, Chi-Yang; Mo, Lein-Ray; Lin, Jaw-Town; Wang, Hsiu-Po; Lee, Ching-Tai

2015-01-01

Abstract Radiofrequency ablation (RFA) and endoscopic submucosal dissection (ESD) can potentially be applied for early esophageal squamous cell neoplasia (ESCN); however, no study has directly compared these 2 modalities. We retrospectively enrolled the patients with flat-type “large” (length ≥3 cm extending ≥1/2 of the circumference of esophagus) early ESCNs treated endoscopically. The main outcome measurements were complete response at 12 months, and adverse events. Of a total of 65 patients, 18 were treated with RFA and 47 with ESD. The procedure time of RFA was significantly shorter than that of ESD (126.6 vs 34.8 min; P < 0.001). The complete resection rate of ESD and complete response rate after primary RFA were 89.3% and 77.8%, respectively. Based on the histological evaluation of the post-ESD specimens showed 14 of 47 (29.8%) had histological upstaging compared with the pre-ESD biopsies, and 4 of them had lymphovascular invasion requiring chemoradiation or surgery. After additional therapy for residual lesions, 46 (97.9%) patients in the ESD group and 17 (94.4%) patients in the RFA group achieved a complete response at 12 months. Four patients (8.5%) developed major procedure-related adverse events in the ESD group, but none in the RFA group. In patients with lesions occupying more than 3/4 of the circumference, a significantly higher risk of esophageal stenosis was noted in the ESD group compared with RFA group (83% vs 27%, P = 0.01), which required more sessions of dilatation to resolve the symptoms (median, 13 vs 3, P = 0.04). There were no procedure-related mortality or neoplastic progression in either group; however, 1 patient who received ESD and 1 who received RFA developed local recurrence during a median follow-up period of 32.4 (range, 13–68) and 18.0 (range, 13–41) months, respectively. RFA and ESD are equally effective in the short-term treatment of early flat large ESCNs; however, more adverse events occur with ESD

Discourse changes in early Alzheimer disease, mild cognitive impairment, and normal aging.

PubMed

Chapman, Sandra Bond; Zientz, Jennifer; Weiner, Myron; Rosenberg, Roger; Frawley, William; Burns, Mary Hope

2002-01-01

The purpose of this study was to determine the sensitivity of discourse gist measures to the early cognitive-linguistic changes in Alzheimer disease (AD) and in the preclinical stages. Differences in discourse abilities were examined in 25 cognitively normal adults, 24 adults with mild probable AD, and 20 adults with mild cognitive impairment (MCI) at gist and detail levels of discourse processing. The authors found that gist and detail levels of discourse processing were significantly impaired in persons with AD and MCI as compared with normal control subjects. Gist-level discourse processing abilities showed minimal overlap between cognitively normal control subjects and those with mild AD. Moreover, the majority of the persons with MCI performed in the range of AD on gist measures. These findings indicate that discourse gist measures hold promise as a diagnostic complement to enhance early detection of AD. Further studies are needed to determine how early the discourse gist deficits arise in AD.

Neoplastic Multifocal Skin Lesions: Biology, Etiology, and Targeted Therapies for Nonmelanoma Skin Cancers.

PubMed

Fernandes, Ana R; Santos, Ana C; Sanchez-Lopez, Elena; Kovačević, Andjekla B; Espina, Marta; Calpena, Ana C; Veiga, Francisco J; Garcia, Maria L; Souto, Eliana B

2018-01-01

Neoplastic skin lesions are multifocal, diffuse skin infiltrations of particular relevance in the differential diagnosis of ulcerative, nodular, or crusting skin lesions. Nonmelanoma skin cancers (NMSCs), namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and also actinic keratosis (AK), are the most common malignant tumors in humans. BCCs do not proliferate rapidly and most of the times do not metastasize, while SCCs are more infiltrative, metastatic, and destructive. AKs are precursor lesions of cutaneous SCCs. The classical therapy of NMSCs makes use of photodynamic therapy associated with chemotherapeutics. With improved understanding of the pathological mechanisms of tumor initiation, progression, and differentiation, a case is made towards the use of targeted chemotherapy with the intent to reduce the cytotoxicity of classical treatments. The present review aims to describe the current state of the art on the knowledge of NMSC, including its risks factors, oncogenes, and skin carcinogenesis, discussing the classical therapy against new therapeutic options. © 2017 S. Karger AG, Basel.

Physical and chemical stability of proflavine contrast agent solutions for early detection of oral cancer.

PubMed