Targeting Super-Enhancers for Disease Treatment and Diagnosis.

PubMed

Shin, Ha Youn

2018-05-10

The transcriptional regulation of genes determines the fate of animal cell differentiation and subsequent organ development. With the recent progress in genome-wide technologies, the genomic landscapes of enhancers have been broadly explored in mammalian genomes, which led to the discovery of novel specific subsets of enhancers, termed superenhancers. Super-enhancers are large clusters of enhancers covering the long region of regulatory DNA and are densely occupied by transcription factors, active histone marks, and co-activators. Accumulating evidence points to the critical role that super-enhancers play in cell type-specific development and differentiation, as well as in the development of various diseases. Here, I provide a comprehensive description of the optimal approach for identifying functional units of superenhancers and their unique chromatin features in normal development and in diseases, including cancers. I also review the recent updated knowledge on novel approaches of targeting super-enhancers for the treatment of specific diseases, such as small-molecule inhibitors and potential gene therapy. This review will provide perspectives on using superenhancers as biomarkers to develop novel disease diagnostic tools and establish new directions in clinical therapeutic strategies.

Breast MRI background parenchymal enhancement (BPE) correlates with the risk of breast cancer.

PubMed

Telegrafo, Michele; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe; Moschetta, Marco

2016-02-01

To investigate whether background parenchymal enhancement (BPE) and breast cancer would correlate searching for any significant difference of BPE pattern distribution in case of benign or malignant lesions. 386 patients, including 180 pre-menopausal (group 1) and 206 post-menopausal (group 2), underwent MR examination. Two radiologists evaluated MR images classifying normal BPE as minimal, mild, moderate or marked. The two groups of patients were subdivided into 3 categories based on MRI findings (negative, benign and malignant lesions). The distribution of BPE patterns within the two groups and within the three MR categories was calculated. The χ2 test was used to evaluate BPE type distribution in the three patient categories and any statistically significant correlation of BPE with lesion type was calculated. The Student t test was applied to search for any statistically significant difference between BPE type rates in group 1 and 2. The χ2 test demonstrated a statistically significant difference in the distribution of BPE types in negative patients and benign lesions as compared with malignant ones (p<0.05). A significantly higher prevalence of moderate and marked BPE was found among malignant lesions (group 1: 32% and 42%, respectively; group 2: 31% and 46%, respectively) while a predominance of minimal and mild BPE among negative patients (group 1: 60% and 36%, respectively; group 2: 68% and 32%, respectively) and benign lesions (group 1: 54% and 38%, respectively; group 2: 75% and 17%, respectively) was found. The Student t test did not show a statistically significant difference between BPE type rates in group 1 and 2 (p>0.05). Normal BPE could correlate with the risk of breast cancer being such BPE patterns as moderate and marked associated with patients with malignant lesions in both pre and post-menopausal women. Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical enhancement of footwear impressions in blood deposited on fabric--evaluating the use of alginate casting materials followed by chemical enhancement.

PubMed

Farrugia, Kevin J; NicDaéid, Niamh; Savage, Kathleen A; Bandey, Helen

2010-12-01

Most footwear marks made in blood on a surface such as fabric tend to be enhanced in situ rather than physically recovered using a lifting technique prior to enhancement. This work reports on the use of an alginate material to recover the impressed footwear marks made in blood and deposited on a range of fabric types and colours. The lifted marks were then enhanced using acid black 1 and leuco crystal violet with excellent results. This presents a new method for the lifting and recovery of blood impressions in situ from crime scene followed by subsequent mark enhancement of the lifted impression. Copyright © 2010 Forensic Science Society. Published by Elsevier Ireland Ltd.. All rights reserved.

HOXB4 overexpression mediates very rapid stem cell regeneration and competitive hematopoietic repopulation.

PubMed

Antonchuk, J; Sauvageau, G; Humphries, R K

2001-09-01

Hox transcription factors have emerged as important regulators of hematopoiesis. In particular, we have shown that overexpression of HOXB4 in mouse bone marrow can greatly enhance the level of hematopoietic stem cell (HSC) regeneration achieved at late times (> 4 months) posttransplantation. The objective of this study was to resolve if HOXB4 increases the rate and/or duration of HSC regeneration, and also to see if this enhancement was associated with impaired production of end cells or would lead to competitive reconstitution of all compartments. Retroviral vectors were generated with the GFP reporter gene +/- HOXB4 to enable the isolation and direct tracking of transduced cells in culture or following transplantation. Stem cell recovery was measured by limit dilution assay for long-term competitive repopulating cells (CRU). HOXB4-overexpressing cells have enhanced growth in vitro, as demonstrated by their rapid dominance in mixed cultures and their shortened population doubling time. Furthermore, HOXB4-transduced cells have a marked competitive repopulating advantage in vivo in both primitive and mature compartments. CRU recovery in HOXB4 recipients was extremely rapid, reaching 25% of normal by 14 days posttransplant or some 80-fold greater than control transplant recipients, and attaining normal numbers by 12 weeks. Mice transplanted with even higher numbers of HOXB4-transduced CRU regenerated up to but not beyond the normal CRU levels. HOXB4 is a potent enhancer of primitive hematopoietic cell growth, likely by increasing self-renewal probability but without impairing homeostatic control of HSC population size or the rate of production and maintenance of mature end cells.

Contrast enhancement of bite mark images using the grayscale mixer in ACR in Photoshop®.

PubMed

Evans, Sam; Noorbhai, Suzanne; Lawson, Zoe; Stacey-Jones, Seren; Carabott, Romina

2013-05-01

Enhanced images may improve bite mark edge definition, assisting forensic analysis. Current contrast enhancement involves color extraction, viewing layered images by channel. A novel technique, producing a single enhanced image using the grayscale mix panel within Adobe Camera Raw®, has been developed and assessed here, allowing adjustments of multiple color channels simultaneously. Stage 1 measured RGB values in 72 versions of a color chart image; eight sliders in Photoshop® were adjusted at 25% intervals, all corresponding colors affected. Stage 2 used a bite mark image, and found only red, orange, and yellow sliders had discernable effects. Stage 3 assessed modality preference between color, grayscale, and enhanced images; on average, the 22 survey participants chose the enhanced image as better defined for nine out of 10 bite marks. The study has shown potential benefits for this new technique. However, further research is needed before use in the analysis of bite marks. © 2013 American Academy of Forensic Sciences.

PSCs and GLP-1R: occurrence in normal pancreas, acute/chronic pancreatitis and effect of their activation by a GLP-1R agonist

PubMed Central

Nakamura, Taichi; Ito, Tetsuhide; Uchida, Masahiko; Hijioka, Masayuki; Igarashi, Hisato; Oono, Takamasa; Kato, Masaki; Nakamura, Kazuhiko; Suzuki, Koichi; Jensen, Robert T.; Takayanagi, Ryoichi

2013-01-01

Background and Aims There is increasing concern about the development of pancreatitis in patients with diabetes mellitus who received long-term GLP-1 analog treatment. Its pathogenesis is unknown. The effects of GLP-1 agonists on pancreatic endocrine cells is well studied, however there is little information on effects on other pancreatic tissues that might be involved in inflammatory processes. Pancreatic stellate cells (PSCs) can play an important role in pancreatitis, secreting various inflammatory cytokines/chemokines, as well as collagen. In this study, we investigated GLP-1R occurrence in normal pancreas, acute/chronic pancreatitis, and the effects of GLP-1 analog on normal PSCs, their ability to stimulate inflammatory mediator secretion or proliferation. Methods GLP-1R expression/localization in normal pancreas and pancreatitis (acute/chronic) tissues were evaluated with histological/immunohistochemical analysis. PSCs were isolated from male Wistar rats. GLP1R expression and effects of GLP-1 analog on activated PSCs was examined with realtime PCR, MTS assays and Western Blotting. Results In normal pancreas, pancreatic β cells expressed GLP-1R, with only low expression in acinar cells, whereas in acute or chronic pancreatitis, acinar cells, ductal cells and activated PSCs expressed GLP-1R. With activation of normal PSCs, GLP-1R is markedly increased, as is multiple other incretin-related receptors. The GLP-1 analog, liraglutide, did not induce inflammatory genes expression in activated PSCs, but induced proliferation. Liraglutide activated multiple signaling cascades in PSCs, and the ERK pathway mediated the PSCs proliferation. Conclusions GLP-1Rs are expressed in normal pancreas and there is marked enhanced expression in acute/chronic pancreatitis. GLP-1-agonist induced cell proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest chronic treatment with GLP-1R agonists could lead to proliferation/chronic activation of PSCs, which may lead to important effects in the pancreas. PMID:24217090

Osthole enhances TRAIL-mediated apoptosis through downregulation of c-FLIP expression in renal carcinoma Caki cells.

PubMed

Min, Kyoung-Jin; Han, Min Ae; Kim, Shin; Park, Jong-Wook; Kwon, Taeg Kyu

2017-04-01

Osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, has been shown to induce various beneficial biochemical effects such as anti-inflammatory and antitumor. In the present study, we examined whether osthole could sensitize TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human renal carcinoma Caki cells. We found that osthole and TRAIL alone, had no effect on apoptosis, but combined treatment with osthole and TRAIL markedly induced apoptosis in Caki (renal carcinoma), U251MG (glioma) and MDA-MB-231 (breast carcinoma) cells. In contrast, combined treatment with osthole and TRAIL did not induce apoptosis in normal human skin fibroblast cells. Osthole induced downregulation of cellular FLICE-like inhibitory protein (c-FLIP) expression, and overexpression of c-FLIP markedly blocked apoptosis induced by the combined treatment with osthole and TRAIL. In addition, osthole markedly reduced mitochondrial membrane potential levels, and increased cytosolic cytochrome c release in combined treatment with osthole and TRAIL. Therefore, these data suggest that osthole may be an efficient TRAIL sensitizer.

Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility

PubMed Central

Seumois, Grégory; Chavez, Lukas; Gerasimova, Anna; Lienhard, Matthias; Omran, Nada; Kalinke, Lukas; Vedanayagam, Maria; Ganesan, Asha Purnima V; Chawla, Ashu; Djukanović, Ratko; Ansel, K Mark; Peters, Bjoern; Rao, Anjana; Vijayanand, Pandurangan

2014-01-01

A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4+ T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis. PMID:24997565

Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility.

PubMed

Seumois, Grégory; Chavez, Lukas; Gerasimova, Anna; Lienhard, Matthias; Omran, Nada; Kalinke, Lukas; Vedanayagam, Maria; Ganesan, Asha Purnima V; Chawla, Ashu; Djukanović, Ratko; Ansel, K Mark; Peters, Bjoern; Rao, Anjana; Vijayanand, Pandurangan

2014-08-01

A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4(+) T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis.

Abnormal cardiovascular response to exercise in hypertension: contribution of neural factors.

PubMed

Mitchell, Jere H

2017-06-01

During both dynamic (e.g., endurance) and static (e.g., strength) exercise there are exaggerated cardiovascular responses in hypertension. This includes greater increases in blood pressure, heart rate, and efferent sympathetic nerve activity than in normal controls. Two of the known neural factors that contribute to this abnormal cardiovascular response are the exercise pressor reflex (EPR) and functional sympatholysis. The EPR originates in contracting skeletal muscle and reflexly increases sympathetic efferent nerve activity to the heart and blood vessels as well as decreases parasympathetic efferent nerve activity to the heart. These changes in autonomic nerve activity cause an increase in blood pressure, heart rate, left ventricular contractility, and vasoconstriction in the arterial tree. However, arterial vessels in the contracting skeletal muscle have a markedly diminished vasoconstrictor response. The markedly diminished vasoconstriction in contracting skeletal muscle has been termed functional sympatholysis. It has been shown in hypertension that there is an enhanced EPR, including both its mechanoreflex and metaboreflex components, and an impaired functional sympatholysis. These conditions set up a positive feedback or vicious cycle situation that causes a progressively greater decrease in the blood flow to the exercising muscle. Thus these two neural mechanisms contribute significantly to the abnormal cardiovascular response to exercise in hypertension. In addition, exercise training in hypertension decreases the enhanced EPR, including both mechanoreflex and metaboreflex function, and improves the impaired functional sympatholysis. These two changes, caused by exercise training, improve the muscle blood flow to exercising muscle and cause a more normal cardiovascular response to exercise in hypertension. Copyright © 2017 the American Physiological Society.

Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function.

PubMed

Won, Hyejung; Lee, Hye-Ryeon; Gee, Heon Yung; Mah, Won; Kim, Jae-Ick; Lee, Jiseok; Ha, Seungmin; Chung, Changuk; Jung, Eun Suk; Cho, Yi Sul; Park, Sae-Geun; Lee, Jung-Soo; Lee, Kyungmin; Kim, Daesoo; Bae, Yong Chul; Kaang, Bong-Kiun; Lee, Min Goo; Kim, Eunjoon

2012-06-13

Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.

Evaluation of serum concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-10, and nitric oxide (NO) during the estrous cycle, early pregnancy and abortion in goats.

PubMed

Chen, Youwang; Lv, Wenting; Jia, Jingliang; Wang, Jiantao; Yang, Jianhui

2016-11-01

The aim of this study was to establish the serum concentrations, ranges, and trends of Th1 type cytokine (tumor necrosis factor (TNF)-α and interleukin (IL)-2), Th2 type cytokine (IL-10), and nitric oxide (NO) during the estrous cycle, early pregnancy and abortion in goats. Boer goats (n=25) having symptoms of normal estrous cycles were selected, 20 were mated and 15 conceived a pregnancy, and the remaining five were not mated and served as estrous controls. On the Day 60 of pregnancy, all 15 pregnant goats were induced to abort the pregnancy by intramuscular injection of prostaglandin (PG). Serum samples were collected on Days 1, 7, 14, and 19 of the estrous cycle, at Days 0, 10, 20, 30, 40, 50, and 60 of pregnancy, and at Days 1, 3, 8, 10 over the period when abortion were occurring. Results of the present study indicated that during the estrous cycle the balance between Th1 and Th2 cytokines slightly shifted toward Th1 cytokine production (TNF-α and IL-2). The NO may have a direct positive role in inducing a Th1 response. During early pregnancy, TNF-α and IL-2 serum concentrations markedly increased from Days 0 to 10, and gradually decreased from Days 10 to 60, while IL-10 and NO serum concentrations remained elevated from Days 0 to 60. The increased concentrations of IL-10 and decreased concentrations of TNF-α and IL-2 are characteristic of a Th2-enhanced response, which may be related to increased concentrations of NO. These changes may be essential to maintain a normal pregnancy. In addition, the serum concentrations of TNF-α, IL-2 and NO at Days 1, 3, 8 and 10 of the period of induced abortion were markedly greater than that on Day 60 of pregnancy. Conversely, IL-10 concentrations at these four time points of abortion were markedly less than that on Day 60 of pregnancy. After abortion, the Th2 response shifted to a Th1-enhanced response. Thus, NO concentrations increase and the Th1-enhanced response may function synergistically to be involved in physiologic responses that lead to abortion of the pregnancy. It is concluded that the serum concentrations of the Th1/Th2 cytokine and NO changed temporally as the estrous cycle, pregnancy and abortion progressed advanced. A Th2-enhanced state promoted normal pregnancy, while increased concentrations of Th1 were observed during the period of fetal abortion. The concentrations of NO varied in regulation of the Th1/Th2 cytokine concentration balance during the three phases (estrous cycle, pregnancy, and fetal abortion) of goats. Copyright © 2016 Elsevier B.V. All rights reserved.

PATHOGENESIS OF FEVER: EFFECTS OF VARIOUS ENDOGENOUS PYROGENS UPON THE LEVEL OF CIRCULATING GRANULOCYTES IN NORMAL RABBITS

PubMed Central

King, M. K.

1960-01-01

The endogenous pyrogen in the serum or plasma of rabbits 2 hours after the intravenous injection of typhoid vaccine had a marked effect on the circulating leucocytes of normal rabbits. Immediately following intravenous injection there was a brief, but marked, granulocytopenia which was quickly followed by a granulocytosis. Under the same circumstances pooled heterologous serum or plasma from normal rabbits produced no fever or significant change in the level of circulating leucocytes. The cell-free fluid of sterile peritoneal exudates produced a marked leucocytosis without a preceding leucopenia when injected intravenously into normal rabbits. When comparably pyrogenic doses of typhoid vaccine were injected in the same manner no significant change in the level of circulating leucocytes occurred. The relevance of these findings to the pathogenesis of fever is discussed. PMID:13756095

Pathogenesis of fever: effects of various endogenous pyrogens upon the level of circulating granulocytes in normal rabbits.

PubMed

KING, M K

1960-11-01

The endogenous pyrogen in the serum or plasma of rabbits 2 hours after the intravenous injection of typhoid vaccine had a marked effect on the circulating leucocytes of normal rabbits. Immediately following intravenous injection there was a brief, but marked, granulocytopenia which was quickly followed by a granulocytosis. Under the same circumstances pooled heterologous serum or plasma from normal rabbits produced no fever or significant change in the level of circulating leucocytes. The cell-free fluid of sterile peritoneal exudates produced a marked leucocytosis without a preceding leucopenia when injected intravenously into normal rabbits. When comparably pyrogenic doses of typhoid vaccine were injected in the same manner no significant change in the level of circulating leucocytes occurred. The relevance of these findings to the pathogenesis of fever is discussed.

Enhanced expression of IL-8 in normal human keratinocytes and human keratinocyte cell line HaCaT in vitro after stimulation with contact sensitizers, tolerogens and irritants.

PubMed

Mohamadzadeh, M; Müller, M; Hultsch, T; Enk, A; Saloga, J; Knop, J

1994-12-01

To investigate the interleukin-8 production of keratinocytes after stimulation in vitro we have used various agents: (i) contact sensitizer (2,4-dinitrofluorobenzene, 3-n-pentadecylcatechol); (ii) tolerogen (5-methyl-3-n-pentadecylcatechol); (iii) irritant (sodium lauryl sulfate). Interleukin-8 gene expression was assessed by northern blot hybridization of the total cytoplasmic RNA extracted from subconfluent normal human keratinocyte cultures and the keratinocyte cell line HaCaT using a radiolabeled DNA probe specific for human interleukin-8. Interleukin-8 gene expression was markedly increased upon in vitro stimulation after 1-6 h with contact sensitizers, tolerogen and the irritant. In contrast, interleukin-8 production was not detectable in unstimulated normal human keratinocytes or the HaCaT keratinocyte cell line. These results suggest that the induction and production of interleukin-8 is a response to nonspecific stimuli and may play a critical role in the early response to immunogenic or inflammatory signals in man.

Evaluation of longitudinal construction joints on traffic operations and safety.

DOT National Transportation Integrated Search

2009-01-01

Motorists generally follow the guidance provided by pavement markings, which are normally marked in : coincidence with the longitudinal construction joints, when the markings are necessary. At some locations, : however, there may be a difference betw...

Acute hyperglycaemia enhances oxidative stress and aggravates myocardial ischaemia/reperfusion injury: role of thioredoxin-interacting protein

PubMed Central

Su, Hui; Ji, Lele; Xing, Wenjuan; Zhang, Wei; Zhou, Heping; Qian, Xinhong; Wang, Xiaoming; Gao, Feng; Sun, Xin; Zhang, Haifeng

2013-01-01

Hyperglycaemia during acute myocardial infarction is common and associated with increased mortality. Thioredoxin-interacting protein (Txnip) is a modulator of cellular redox state and contributes to cell apoptosis. This study aimed to investigate whether or not hyperglycaemia enhances Txnip expression in myocardial ischaemia/reperfusion (MI/R) and consequently exacerbates MI/R injury. Rats were subjected to 30 min. of left coronary artery ligation followed by 4 hrs of reperfusion and treated with saline or high glucose (HG, 500 g/l, 4 ml/kg/h intravenously). In vitro study was performed on cultured rat cardiomyocytes subjected to simulated ischaemia/reperfusion (SI/R) and incubated with HG (25 mM) or normal glucose (5.6 mM) medium. In vivo HG infusion during MI/R significantly impaired cardiac function, aggravated myocardial injury and increased cardiac oxidative stress. Meanwhile, Txnip expression was enhanced whereas thioredoxin activity was inhibited following HG treatment in ischaemia/reperfusion (I/R) hearts. In addition, HG activated p38 MAPK and inhibited Akt in I/R hearts. In cultured cardiomyocytes subjected to SI/R, HG incubation stimulated Txnip expression and reduced thioredoxin activity. Overexpression of Txnip enhanced HG-induced superoxide generation and aggravated cardiomyocyte apoptosis, whereas Txnip RNAi significantly blunted the deleterious effects of HG. Moreover, inhibition of p38 MAPK or activation of Akt markedly blocked HG-induced Txnip expression in I/R cardiomyocytes. Most importantly, intramyocardial injection of Txnip siRNA markedly decreased Txnip expression and alleviated MI/R injury in HG-treated rats. Hyperglycaemia enhances myocardial Txnip expression, possibly through reciprocally modulating p38 MAPK and Akt activation, leading to aggravated oxidative stress and subsequently, amplification of cardiac injury following MI/R. PMID:23305039

46 CFR 46.15-10 - Subdivision load lines.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 and a “diamond” shall be substituted for the “disk”. No “fresh water” line will be marked. [CGFR... located in line with the highest subdivision load line. (f) One fresh water line shall be marked. When a subdivision and a normal load line are combined, the normal fresh water line only shall be used unless the...

MARK2/EMK1/Par-1Balpha phosphorylation of Rab11-family interacting protein 2 is necessary for the timely establishment of polarity in Madin-Darby canine kidney cells.

PubMed

Ducharme, Nicole A; Hales, Chadwick M; Lapierre, Lynne A; Ham, Amy-Joan L; Oztan, Asli; Apodaca, Gerard; Goldenring, James R

2006-08-01

Rab11a, myosin Vb, and the Rab11-family interacting protein 2 (FIP2) regulate plasma membrane recycling in epithelial cells. This study sought to characterize more fully Rab11-FIP2 function by identifying kinase activities modifying Rab11-FIP2. We have found that gastric microsomal membrane extracts phosphorylate Rab11-FIP2 on serine 227. We identified the kinase that phosphorylated Rab11-FIP2 as MARK2/EMK1/Par-1Balpha (MARK2), and recombinant MARK2 phosphorylated Rab11-FIP2 only on serine 227. We created stable Madin-Darby canine kidney (MDCK) cell lines expressing enhanced green fluorescent protein-Rab11-FIP2 wild type or a nonphosphorylatable mutant [Rab11-FIP2(S227A)]. Analysis of these cell lines demonstrates a new role for Rab11-FIP2 in addition to that in the plasma membrane recycling system. In calcium switch assays, cells expressing Rab11-FIP2(S227A) showed a defect in the timely reestablishment of p120-containing junctional complexes. However, Rab11-FIP2(S227A) did not affect localization with recycling system components or the normal function of apical recycling and transcytosis pathways. These results indicate that phosphorylation of Rab11-FIP2 on serine 227 by MARK2 regulates an alternative pathway modulating the establishment of epithelial polarity.

Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab

PubMed Central

Lassau, N.; Coiffier, B.; Kind, M.; Vilgrain, V.; Lacroix, J.; Cuinet, M.; Taieb, S.; Aziza, R.; Sarran, A.; Labbe-Devilliers, C.; Gallix, B.; Lucidarme, O.; Ptak, Y.; Rocher, L.; Caquot, L. M.; Chagnon, S.; Marion, D.; Luciani, A.; Feutray, S.; Uzan-Augui, J.; Benatsou, B.; Bonastre, J.; Koscielny, S.

2016-01-01

Background Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. Patients and methods Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. Results The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. Conclusion The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. AFSSAPS No 2007-A00399-44. PMID:27502701

A novel mode of enhancer evolution: The Tal1 stem cell enhancer recruited a MIR element to specifically boost its activity

PubMed Central

Smith, Aileen M.; Sanchez, Maria-Jose; Follows, George A.; Kinston, Sarah; Donaldson, Ian J.; Green, Anthony R.; Göttgens, Berthold

2008-01-01

Altered cis-regulation is thought to underpin much of metazoan evolution, yet the underlying mechanisms remain largely obscure. The stem cell leukemia TAL1 (also known as SCL) transcription factor is essential for the normal development of blood stem cells and we have previously shown that the Tal1 +19 enhancer directs expression to hematopoietic stem cells, hematopoietic progenitors, and to endothelium. Here we demonstrate that an adjacent region 1 kb upstream (+18 element) is in an open chromatin configuration and carries active histone marks but does not function as an enhancer in transgenic mice. Instead, it boosts activity of the +19 enhancer both in stable transfection assays and during differentiation of embryonic stem (ES) cells carrying single-copy reporter constructs targeted to the Hprt locus. The +18 element contains a mammalian interspersed repeat (MIR) which is essential for the +18 function and which was transposed to the Tal1 locus ∼160 million years ago at the time of the mammalian/marsupial branchpoint. Our data demonstrate a previously unrecognized mechanism whereby enhancer activity is modulated by a transposon exerting a “booster” function which would go undetected by conventional transgenic approaches. PMID:18687876

Gamma-irradiation enhances apoptosis induced by cannabidiol, a non-psychotropic cannabinoid, in cultured HL-60 myeloblastic leukemia cells.

PubMed

Gallily, Ruth; Even-Chena, Tal; Katzavian, Galia; Lehmann, Dan; Dagan, Arie; Mechoulam, Raphael

2003-10-01

Two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabidiol-dimethylheptyl (CBD-DMH), induced apoptosis in a human acute myeloid leukemia (AML) HL-60 cell line. Apoptosis was determined by staining with bisBenzimide and propidium iodide. A dose dependent increase of apoptosis was noted, reaching 61 and 43% with 8 microg/ml CBD and 15 microg/ml CBD-DMH, respectively, after a 24 h treatment. Prior exposure of the cells to gamma-irradiation (800 cGy) markedly enhanced apoptosis, reaching values of 93 and 95%, respectively. Human monocytes from normal individuals were resistant to either cannabinoids or gamma-irradiation. Caspase-3 activation was observed after the cannabinoid treatment, and may represent a mechanism for the apoptosis. Our data suggest a possible new approach to treatment of AML.

Liver injury in hypervitaminosis A: Evidence for activation of Kupffer cell function

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

Sim, W.L.W.

1988-01-01

The most important and novel finding of this work was enhanced liver Kupffer cell phagocytic and metabolic function by hypervitaminosis A. An animal model of hypervitaminosis A was developed in male Sprague-Dawley rats gavaged with 250,000 I.U. retinol/kg body weight/day for 3 weeks. Presence of hypervitaminosis A was indicated by characteristic changes in the fur coat, presence of brittle bones and spontaneous fractures and a significant increase in plasma and liver concentrations of retinyl palmitate while retinol levels remained the same as in controls. Hypervitaminosis A did not cause severe liver abnormalities as reflected by normal plasma glutamate pyruvate transaminasemore » activity and bilirubin. The main change was a marked increase in size of the fat or Vitamin A storing cells. Measurement of clearance from blood of indocyanine green and {sup 99m}Tc-disofenin indicated this hepatocyte function was normal. Kupffer cell phagocytic function was enhanced in hypervitaminosis A as determined by clearance from blood of {sup 99m}Tc-sulfur colloid. In vitro, there was also evidence that treatment with high doses of Vitamin A activated or enhanced Kupffer cell function. Kupffer cells from control and Vitamin A treated rats were isolated by enzymatic dispersion, purified by centrifugal elutriation, and placed in culture. Activation was indicated by (1) increased phagocytosis of {sup 51}Cr-labeled opsonized sheep red blood cells (2) enhanced release of superoxide anion and (3) enhanced production of tumor cytolytic factor by Kupffer cells from Vitamin A treated rats.« less

The influence of nerve section on the metabolism of polyamines in rat diaphragm muscle.

PubMed Central

Hopkins, D; Manchester, K L

1981-01-01

Concentrations of spermidine, spermine and putrescine have been measured in rat diaphragm muscle after unilateral nerve section. The concentration of putrescine increased approx. 10-fold 2 days after nerve section, that of spermidine about 3-fold by day 3, whereas an increase in the concentration of spermine was only observed after 7-10 days. It was not possible to show enhanced uptake of either exogenous putrescine or spermidine by the isolated tissue during the hypertrophy. Consistent with the accumulation of putrescine, activity of ornithine decarboxylase increased within 1 day of nerve section, was maximally elevated by the second day and then declined. Synthesis of spermidine from [14C]putrescine and either methionine or S-adenosylmethionine bt diaphragm cytosol rose within 1 day of nerve section, but by day 3 had returned to normal or below normal values. Activity of adenosylmethionine decarboxylase similarly increased within 1 day of nerve section, but by day 3 had declined to below normal values. Activity of methionine adenosyltransferase was elevated throughout the period studied. The concentration of S-adenosylmethionine was likewise enhanced during hypertrophy. Administration of methylglyoxal bis(guanylhydrazone) produced a marked increase in adenosylmethionine decarboxylase activity and a large increase in putrescine concentration, but did not prevent the rise in spermidine concentration produced by denervation. Possible regulatory mechanisms of polyamine metabolism consistent with the observations are discussed. PMID:7316998

Enhanced G2 chromatid radiosensitivity, an early stage in the neoplastic transformation of human epidermal keratinocytes in culture

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

Gantt, R.; Sanford, K.K.; Parshad, R.

1987-03-01

A deficiency in DNA repair, manifest as enhanced chromatid radiosensitivity during the G2 phase of the cell cycle, together with a proliferative stimulus such as that provided by active oncogenes may be necessary and sufficient for the malignant neoplastic transformation of human keratinocytes in culture. Normal epidermal keratinocytes established as continuous cell lines by transfection with pSV3-neo or infection with adeno 12-SV40 hybrid virus developed enhanced G2 chromatid radiosensitivity after 18 passages in culture. In contrast to cells from primary or secondary culture, these cells could be transformed to malignant neoplastic cells by infection with Kirsten murine sarcoma virus containingmore » the Ki-ras oncogene or in one line by the chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine; both of these agents produced a marked proliferative response. Cytological heterogeneity and karyotypic instability characterized the cells during their progression to neoplasia. These results are interpreted in terms of a mechanism for neoplastic transformation.« less

Natural killer cell activity, lymphocyte proliferation, and cytokine profile in tumor-bearing mice treated with MAPA, a magnesium aggregated polymer from Aspergillus oryzae.

PubMed

Justo, G Z; Durán, N; Queiroz, M L S

2003-08-01

The present study examined the effects of MAPA, an antitumor aggregated polymer of protein magnesium ammonium phospholinoleate-palmitoleate anhydride, isolated from Aspergillus oryzae, on concanavalin A (Con A)-induced spleen cell proliferation, cytokine production and on natural killer (NK) cell activity in Ehrlich ascites tumor-bearing mice. The Ehrlich ascites tumor (EAT) growth led to diminished mitogen-induced expansion of spleen cell populations and total NK activity. This was accompanied by striking spleen enlargement, with a marked increase in total cell counts. Moreover, a substantial enhancement in IL-10 levels, paralleled by a significant decrease in IL-2 was observed, while production of IL-4 and interferon-gamma (IFN-gamma) was not altered. Treatment of mice with 5 mg/kg MAPA for 7 days promoted spleen cell proliferation, IL-2 production and NK cell activity regardless of tumor outgrowth. In addition, MAPA treatment markedly enhanced IFN-gamma levels and reduced IL-10 production relative to EAT mice. A 35% reduction in splenomegaly with normal number of nucleated cells was also found. Altogether, our results suggest that MAPA directly and/or indirectly modulates immune cell activity, and probably disengages tumor-induced suppression of these responses. Clearly, MAPA has an impact and may delay tumor outgrowth through immunotherapeutic mechanisms.

Repair of traumatized mammalian hair cells via sea anemone repair proteins.

PubMed

Tang, Pei-Ciao; Smith, Karen Müller; Watson, Glen M

2016-08-01

Mammalian hair cells possess only a limited ability to repair damage after trauma. In contrast, sea anemones show a marked capability to repair damaged hair bundles by means of secreted repair proteins (RPs). Previously, it was found that recovery of traumatized hair cells in blind cavefish was enhanced by anemone-derived RPs; therefore, the ability of anemone RPs to assist recovery of damaged hair cells in mammals was tested here. After a 1 h incubation in RP-enriched culture media, uptake of FM1-43 by experimentally traumatized murine cochlear hair cells was restored to levels comparable to those exhibited by healthy controls. In addition, RP-treated explants had significantly more normally structured hair bundles than time-matched traumatized control explants. Collectively, these results indicate that anemone-derived RPs assist in restoring normal function and structure of experimentally traumatized hair cells of the mouse cochlea. © 2016. Published by The Company of Biologists Ltd.

A Case of Extrahepatic Portal Vein Aneurysm Complicated by Acute Thrombosis.

PubMed

Kim, Hye Jin; Ha, Tae-Yong; Ko, Gi-Young; Noh, Minsu; Kwon, Tae-Won; Cho, Yong-Pil; Lee, Sung-Gyu

2017-08-01

Portal vein (PV) aneurysm is a rare disease entity, and the optimal strategy for its management remains unclear. We describe the case of a 34-year-old woman who was incidentally diagnosed with an asymptomatic extrahepatic PV aneurysm. Although expectant management with regular follow-up and surveillance imaging was adopted, the PV aneurysm progressed into a symptomatic type, accompanied by complications of acute thrombosis. Hence, an aneurysm excision with interposition bypass was performed. Her postoperative recovery was rapid and uneventful, with liver function test results within normal ranges and normal portal flow on color Doppler ultrasonography and contrast-enhanced computed tomography. The incidence of thromboses among the reported PV aneurysm cases may be markedly high, and early surgical intervention for low-risk patients may therefore be required to prevent the development of portal hypertension with clinically severe consequences. Copyright © 2017 Elsevier Inc. All rights reserved.

Thermal inertia mapping of below ground objects and voids

NASA Astrophysics Data System (ADS)

Del Grande, Nancy K.; Ascough, Brian M.; Rumpf, Richard L.

2013-05-01

Thermal inertia (effusivity) contrast marks the borders of naturally heated below ground object and void sites. The Dual Infrared Effusivity Computed Tomography (DIRECT) method, patent pending, detects and locates the presence of enhanced heat flows from below ground object and void sites at a given area. DIRECT maps view contrasting surface temperature differences between sites with normal soil and sites with soil disturbed by subsurface, hollow or semi-empty object voids (or air gaps) at varying depths. DIRECT utilizes an empirical database created to optimize the scheduling of daily airborne thermal surveys to view and characterize unseen object and void types, depths and volumes in "blind" areas.

Relationship of the Structure of Bacterial Lipopolysaccharides to Its Function in Mitogenesis and Adjuvanticity

PubMed Central

Chiller, Jacques M.; Skidmore, Barry J.; Morrison, David C.; Weigle, William O.

1973-01-01

The ability of bacterial lipopolysaccharides to induce lymphocyte mitogenesis and to act as an adjuvant of antibody formation was attributable to the lipid-A region of the molecule. Measured by induction of DNA synthesis, lipid A was mitogenic for bone marrow-derived lymphocytes obtained from spleens of congenitally athymic mice but not for thymocytes obtained from thymuses of normal mice. Adjuvanticity was demonstrated by the ability of lipid A to convert a tolerogenic regimen of antigen into one eliciting an immune response and by its ability to markedly enhance the antibody response to a weak antigen. PMID:4579014

76 FR 33023 - Safety Advisory; Unauthorized Marking of Compressed Gas Cylinders

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-07

... cylinders. The cylinders were neither marked nor certified by an authorized independent inspection agency... mark, the cylinder did not undergo the complete series of safety tests and inspections required by the... contents under pressure during normal transportation and use. Extensive property damage, serious personal...

Enhanced degradation of p53 protein in HPV-6 and BPV-1 E6-immortalized human mammary epithelial cells.

PubMed Central

Band, V; Dalal, S; Delmolino, L; Androphy, E J

1993-01-01

Normal mammary epithelial cells are efficiently immortalized by the E6 gene of human papillomavirus (HPV)-16, a virus commonly associated with cervical cancers. Surprisingly, introduction of the E6 gene from HPV-6, which is rarely found in cervical cancer, or bovine papillomavirus (BPV)-1, into normal mammary cells resulted in the generation of immortal cell lines. The establishment of HPV-6 and BPV-1 E6-immortalized cells was less efficient and required a longer period in comparison to HPV-16 E6. These HPV-6- and BPV-1 E6-immortalized cells demonstrated dramatically reduced levels of p53 protein by immunoprecipitation. While the half-life of p53 protein in normal mammary epithelial cells was approximately 3 h, it was reduced to approximately 15 min in all the E6-immortalized cells. These results demonstrate that the E6 genes of both high-risk and low-risk papilloma viruses immortalize human mammary epithelial cells and induce a marked degradation of p53 protein in vivo. Images PMID:8387914

Decursin enhances TRAIL-induced apoptosis through oxidative stress mediated- endoplasmic reticulum stress signalling in non-small cell lung cancers.

PubMed

Kim, Jaekwang; Yun, Miyong; Kim, Eun-Ok; Jung, Deok-Beom; Won, Gunho; Kim, Bonglee; Jung, Ji Hoon; Kim, Sung-Hoon

2016-03-01

The TNF-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent due to its remarkable ability to selectively kill tumour cells. However, because most tumours exhibit resistance to TRAIL-induced apoptosis, the development of combination therapies to overcome resistance to TRAIL is required for effective cancer therapy. Cell viability and possible synergy between the plant pyranocoumarin decursin and TRAIL was measured by MTT assay and calcusyn software. Reactive oxygen species (ROS) and apoptosis were measured using dichlorodihydrofluorescein and annexin/propidium iodide in cell flow cytometry. Changes in protein levels were assessed with Western blotting. Combining decursin and TRAIL markedly decreased cell viability and increased apoptosis in TRAIL-resistant non-small-cell lung cancer (NSCLC) cell lines. Decursin induced expression of the death receptor 5 (DR5). Inhibition of DR5 attenuated apoptotic cell death in decursin + TRAIL treated NSCLC cell lines. Interestingly, induction of DR5 and CCAAT/enhancer-binding protein homologues protein by decursin was mediated through selective induction of the pancreatic endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) branch of the endoplasmic reticulum stress response pathway. Furthermore, enhancement of PERK/ATF4 signalling by decursin was mediated by ROS generation in NSCLC cell lines, but not in normal human lung cells. Decursin also markedly down-regulated expression of survivin and Bcl-xL in TRAIL-resistant NSCLC cells. ROS generation by decursin selectively activated the PERK/ATF4 axis of the endoplasmic reticulum stress signalling pathway, leading to enhanced TRAIL sensitivity in TRAIL-resistant NSCLC cell lines, partly via up-regulation of DR5. © 2015 The British Pharmacological Society.

The influence of low protein diet on the testicular toxicity of di(2-ethylhexyl)phthalate.

PubMed

Tandon, R; Paramar, D; Singh, G B; Seth, P K; Srivastava, S P

1992-12-01

Oral administration of di(2-ethylhexyl)phthalate (DEHP) at 1000 mg/kg body weight to adult male albino rats maintained on low protein (LP) diet for 15 d resulted in a greater decrease in absolute and relative weights of the testis and in epididymal sperm count than in those rats maintained on a normal protein (NP) diet. A marked increase in the activity of testicular beta-glucuronidase and gamma-glutamyl transpeptidase (GGT) in the LP-fed animals suggested that LP diet enhanced the vulnerability of Sertoli cells towards DEHP. A greater decrease in the activity of testicular acid phosphatase, lactate dehydrogenase isoenzyme-X (LDH-X) and sorbitol dehydrogenase (SDH) in the LP-fed animals occurred in comparison to NP-fed animals. Degeneration of mature germinal cells in the LP-fed animals on exposure to DEHP suggested that LP diets enhance the susceptibility of the testis towards DEHP.

Mass marking of juvenile Schizothorax wangchiachii (Fang) with alizarin red S and evaluation of stock enhancement in the Jinping area of the Yalong River

PubMed Central

Yang, Kun; Li, Shu; Liu, Xiaoshuai; Gan, Weixiong; Deng, Longjun; Tang, Yezhong

2017-01-01

Schizothorax wangchiachii is a key fish species in the stock enhancement program of the Yalong River hydropower project, China. Alizarin red S (ARS) was used to mark large numbers of juvenile S. wangchiachii in the Jinping Hatchery and later used to evaluate stock enhancement in the Jinping area of the Yalong River. In a small-scale pilot study, 7,000 juveniles of the 2014 cohort were successfully marked by immersion in ARS solution, and no mortality was recorded during the marking process. The ARS mark in the fish otoliths remained visible 20 months later. In the large-scale marking study, approximately 600,000 juveniles of the 2015 cohort were successfully marked. Mortalities of both marked and unmarked juveniles were very low and did not differ significantly. Total length, wet mass and condition factor did not differ significantly between unmarked and marked individuals after three months. On 24 July 2015, about 840,000 Jinping Hatchery-produced young S. wangchiachii, including 400,000 marked individuals, were released at two sites in the Jinping area. Recapture surveys showed that (1) marked and unmarked S. wangchiachii did not differ significantly in total length, wet mass and condition factor; (2) stocked individuals became an important part of recruitment of the 2015 cohort; (3) instantaneous growth rate of marked individuals tended to slightly increase; and (4) most stocked individuals were distributed along a 10–15 km stretch near the release sites. These results suggest that the ARS method is a cost-efficient way to mass mark juvenile S. wangchiachii and that releasing juveniles is an effective means of stock recruitment. PMID:29230371

Blocking oxytocin receptors inhibits vaginal marking to male odors in female Syrian hamsters.

PubMed

Martinez, Luis A; Albers, H Elliott; Petrulis, Aras

2010-12-02

In Syrian hamsters (Mesocricetus auratus), precopulatory behaviors such as vaginal scent marking are essential for attracting a suitable mate. Vaginal marking is dependent on forebrain areas implicated in the neural regulation of reproductive behaviors in rodents, including the medial preoptic/anterior hypothalamus (MPOA-AH). Within MPOA-AH, the neuropeptide oxytocin (OT) acts to facilitate copulation (lordosis), as well as ultrasonic vocalizations towards males. It is not known, however, if OT in this area also facilitates vaginal marking. In the present study, a specific oxytocin receptor antagonist (OTA) was injected into MPOA-AH of intact female Syrian hamsters to determine if oxytocin receptor-dependent signaling is critical for the normal expression of vaginal marking elicited by male, female, and clean odors. OTA injections significantly inhibited vaginal marking in response to male odors compared with vehicle injections. There was no effect of OTA on marking in response to either female or clean odors. When injected into the bed nucleus of the stria terminalis (BNST), a nearby region to MPOA-AH, OTA was equally effective in decreasing marking. Finally, the effects of OTA appear to be specific to vaginal marking, as OTA injections in MPOA-AH or BNST did not alter general locomotor activity, flank marking, or social odor investigation. Considered together, these results suggest that OT in MPOA-AH and/or BNST normally facilitates male odor-induced vaginal marking, providing further evidence that OT generally supports prosocial interactions among conspecifics. Copyright © 2010 Elsevier Inc. All rights reserved.

Solar flare induced ionospheric D-region enhancements from VLF amplitude observations

NASA Astrophysics Data System (ADS)

Thomson, N. R.; Clilverd, M. A.

2001-11-01

Enhancements of D-region electron densities caused by solar flares are determined from observations of VLF subionospheric amplitude changes and these enhancements are then related to the magnitudes of the X-ray fluxes measured by the GOES satellites. The electron densities are characterised by the two traditional parameters, /H' and /β (being measures of the ionospheric height and the rate of increase of electron density with height, respectively), which are found by VLF radio modelling of the observed amplitudes using the NOSC Earth-ionosphere waveguide programs (LWPC and Modefinder) mainly on two paths, one short and one long. The short path measurements were made near Cambridge, UK, on the 18.3kHz signals from the French transmitter 617km to the south while the long path measurements were made near Dunedin, NZ, on the 24.8kHz signals from NLK in Seattle, USA, 12.3Mm across the Pacific Ocean. The observations include flares up to a magnitude of about M5 (5×10-5Wm-2 at 0.1-0.8nm) which gave VLF amplitude enhancements up to about 8dB; these corresponded, under near solar maximum conditions (1992), to a reduction in /H' from about 71km down to about 63km and an increase in /β from 0.43km-1 up to about 0.49km-1. The increased values of /β during a flare are caused by the solar X-rays dominating all sources of ionisation during the flare in contrast with the normal unperturbed daytime values of /β which are significantly lower than for a single solar UV or X-ray source due to the extra electrons from the normal galactic cosmic ray ionisation in the lowest parts of the D-region. This steady, normal (unperturbed) cosmic ray influence on /β, and hence unperturbed VLF attenuation, is more marked at times of reduced solar Lyman-/α flux in the D-region such as at solar minimum, high latitudes or early or late in the day, thus explaining the normal (unperturbed) higher VLF attenuation rates previously reported in these conditions.

Up-regulation of 5-lipoxygenase by inhibition of cathepsin G enhances TRAIL-induced apoptosis through down-regulation of survivin

PubMed Central

Woo, Seon Min; Min, Kyoung-Jin; Seo, Seung Un; Kim, Shin; Park, Jong-Wook; Song, Dae Kyu; Lee, Hyun-Shik; Kim, Sang Hyun; Kwon, Taeg Kyu

2017-01-01

Cathepsin G is a serine protease secreted from activated neutrophils, it has important roles in inflammation and immune response. Moreover, cathepsin G promotes tumor cell-cell adhesion and migration in cancer cells. In this study, we investigated whether inhibition of cathepsin G could sensitize TRAIL-mediated apoptosis in cancer cells. An inhibitor of cathepsin G [Cathepsin G inhibitor I (Cat GI); CAS 429676-93-7] markedly induced TRAIL-mediated apoptosis in human renal carcinoma (Caki, ACHN, and A498), lung cancer (A549) and cervical cancer (Hela) cells. In contrast, combined treatment with Cat GI and TRAIL had no effect on apoptosis in normal cells [mesangial cell (MC) and human skin fibroblast (HSF)]. Cat GI induced down-regulation of survivin expression at the post-translational level, and overexpression of survivin markedly blocked apoptosis induced by combined treatment with Cat GI plus TRAIL. Interestingly, Cat GI induced down-regulation of survivin via 5-lipoxygenase (5-LOX)-mediated reactive oxygen species (ROS) production. Inhibition of 5-LOX by gene silencing (siRNA) or a pharmacological inhibitor of 5-LOX (zileuton) markedly attenuated combined treatment-induced apoptosis. Taken together, our results indicate that inhibition of cathepsin G sensitizes TRAIL-induced apoptosis through 5-LOX-mediated down-regulation of survivin expression. PMID:29290980

Transient receptor potential vanilloid type 2 (TRPV2) expression in normal urothelium and in urothelial carcinoma of human bladder: correlation with the pathologic stage.

PubMed

Caprodossi, Sara; Lucciarini, Roberta; Amantini, Consuelo; Nabissi, Massimo; Canesin, Giacomo; Ballarini, Patrizia; Di Spilimbergo, Adriana; Cardarelli, Marco Andrea; Servi, Lucilla; Mammana, Gabriele; Santoni, Giorgio

2008-09-01

To evaluate the expression of transient receptor potential vanilloid type 2 (TRPV2) in normal human bladder and urothelial carcinoma (UC) tissues. Bladder specimens were obtained by transurethral resection or radical cystectomy. TRPV2 mRNA expression in normal human urothelial cells (NHUCs), UC cell lines, and formalin-fixed paraffin-embedded normal (n=6) and cancer bladder tissues (n=58) was evaluated by polymerase chain reaction (PCR) and quantitative real-time PCR (RT-PCR). TRPV2 protein expression was assessed by cytofluorimetric and confocal microscopy analyses in NHUCs and UC cells and by Western blotting and immunohistochemistry in normal and UC tissues. Enhanced TRPV2 mRNA and protein expression was found in high-grade and -stage UC specimens and UC cell lines. Both the full-length TRPV2 (hTRPV2) and a short splice-variant (s-TRPV2) were detected in NHUC and normal bladder specimens, whereas a progressive decline of s-TRPV2 in pTa, pT1, and pT2 stages was observed, up to a complete loss in pT3 and pT4 UC specimens. Normal human urothelial cells and bladder tissue specimens express TRPV2 at both the mRNA and protein levels. A progressive loss of s-TRPV2 accompanied by a marked increase of hTRPV2 expression was found in high-grade and -stage UC tissues.

Unequal Probability Marking Approach to Enhance Security of Traceback Scheme in Tree-Based WSNs.

PubMed

Huang, Changqin; Ma, Ming; Liu, Xiao; Liu, Anfeng; Zuo, Zhengbang

2017-06-17

Fog (from core to edge) computing is a newly emerging computing platform, which utilizes a large number of network devices at the edge of a network to provide ubiquitous computing, thus having great development potential. However, the issue of security poses an important challenge for fog computing. In particular, the Internet of Things (IoT) that constitutes the fog computing platform is crucial for preserving the security of a huge number of wireless sensors, which are vulnerable to attack. In this paper, a new unequal probability marking approach is proposed to enhance the security performance of logging and migration traceback (LM) schemes in tree-based wireless sensor networks (WSNs). The main contribution of this paper is to overcome the deficiency of the LM scheme that has a higher network lifetime and large storage space. In the unequal probability marking logging and migration (UPLM) scheme of this paper, different marking probabilities are adopted for different nodes according to their distances to the sink. A large marking probability is assigned to nodes in remote areas (areas at a long distance from the sink), while a small marking probability is applied to nodes in nearby area (areas at a short distance from the sink). This reduces the consumption of storage and energy in addition to enhancing the security performance, lifetime, and storage capacity. Marking information will be migrated to nodes at a longer distance from the sink for increasing the amount of stored marking information, thus enhancing the security performance in the process of migration. The experimental simulation shows that for general tree-based WSNs, the UPLM scheme proposed in this paper can store 1.12-1.28 times the amount of stored marking information that the equal probability marking approach achieves, and has 1.15-1.26 times the storage utilization efficiency compared with other schemes.

Unequal Probability Marking Approach to Enhance Security of Traceback Scheme in Tree-Based WSNs

PubMed Central

Huang, Changqin; Ma, Ming; Liu, Xiao; Liu, Anfeng; Zuo, Zhengbang

2017-01-01

Fog (from core to edge) computing is a newly emerging computing platform, which utilizes a large number of network devices at the edge of a network to provide ubiquitous computing, thus having great development potential. However, the issue of security poses an important challenge for fog computing. In particular, the Internet of Things (IoT) that constitutes the fog computing platform is crucial for preserving the security of a huge number of wireless sensors, which are vulnerable to attack. In this paper, a new unequal probability marking approach is proposed to enhance the security performance of logging and migration traceback (LM) schemes in tree-based wireless sensor networks (WSNs). The main contribution of this paper is to overcome the deficiency of the LM scheme that has a higher network lifetime and large storage space. In the unequal probability marking logging and migration (UPLM) scheme of this paper, different marking probabilities are adopted for different nodes according to their distances to the sink. A large marking probability is assigned to nodes in remote areas (areas at a long distance from the sink), while a small marking probability is applied to nodes in nearby area (areas at a short distance from the sink). This reduces the consumption of storage and energy in addition to enhancing the security performance, lifetime, and storage capacity. Marking information will be migrated to nodes at a longer distance from the sink for increasing the amount of stored marking information, thus enhancing the security performance in the process of migration. The experimental simulation shows that for general tree-based WSNs, the UPLM scheme proposed in this paper can store 1.12–1.28 times the amount of stored marking information that the equal probability marking approach achieves, and has 1.15–1.26 times the storage utilization efficiency compared with other schemes. PMID:28629135

Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

PubMed Central

Szliszka, Ewelina; Czuba, Zenon P; Mazur, Bogdan; Sedek, Lukasz; Paradysz, Andrzej; Krol, Wojciech

2009-01-01

Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showed that all five tested chalcones: chalcone, licochalcone-A, isobavachalcone, xanthohumol, butein markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer. PMID:20161998

Determining the Effectiveness of Visual Input Enhancement across Multiple Linguistic Cues

ERIC Educational Resources Information Center

Comeaux, Ian; McDonald, Janet L.

2018-01-01

Visual input enhancement (VIE) increases the salience of grammatical forms, potentially facilitating acquisition through attention mechanisms. Native English speakers were exposed to an artificial language containing four linguistic cues (verb agreement, case marking, animacy, word order), with morphological cues either unmarked, marked in the…

[Sodium ferulate treatment and interventional mechanism reverse erectile dysfunction in streptozotocin-induced diabetic rats].

PubMed

Xu, Xiao-Hong; Tan, Fu-Qing; Zhao, Tong-Feng; Hu, Hua; Xiao, Kun; Gu, Wei

2009-06-23

To investigate the effect and mechanism of sodium ferulate (SF) on reversing erectile dysfunction in diabetes mellitus (DM) rats. Forty-four male adult Sprague-Dawley rats were induced for diabetes by an intraperitoneal injection of streptozotocin. Then the successful models were randomly divided into DM + SF group and DM group (22 rats each respectively). The rats in DM +SF group were treated with sodium ferulate (100 mg x kg(-1) x d(-1)) through a daily gastric lavage. At Week 12, the erectile function of all rats was evaluated and serum samples were harvested. The SOD, CAT, NOS, MDA and NO levels in corpus cavernosum and serum were all measured. The pathologic change in penile cavernous body was observed microscopically. The diabetic rat models were successfully established. The erectile function was much better in normal control group and DM + SF group than that in DM group. And the penile erection rates in three groups were 100%, 66% and 22% respectively. The activity levels of SOD, CAT and NOS were markedly decreased in DM group as compared to those in normal control group and DM + SF group (P < 0.01). The NO content was approximately equal in normal control group and DM + SF group (112 +/- 28) nmol/ml vs (137 +/- 25) nmol/ml. But both were much higher than that in DM group (56 +/- 10) nmol/ml, both P < 0.01. The MDA content was markedly increased in DM group as compared to those in normal control group and DM + SF group (both P < 0.01). Microscopically, muscle fibers in penile cavernous body arranged disorderly, muscular mantle damaged and desmoplasia scattered among muscle fibers in DM group. Sodium ferulate may play interventional roles in reversing diabetic erectile dysfunction through metabolic regulation of free radicals, antagonism of oxidative insults and enhancement of NO production.

Effects of Coating a Titanium Alloy with Fibronectin on the Expression of Osteoblast Gene Markers in the MC3T3 Osteoprogenitor Cell Line

PubMed Central

Rapuano, Bruce E.; Hackshaw, Kyle M.; Schniepp, Hannes C.; MacDonald, Daniel E.

2013-01-01

Purpose A number of environmental and patient-related factors contribute to implant failure. A significant fraction of these failures can be attributed to limited osseointegration resulting from poor bone healing responses. The overall goal of this study was to determine whether surface treatment of a titanium-aluminum-vanadium alloy (Ti-6Al-4V) implant material with a biomimetic protein coating could promote the differentiation of attached osteoblastic cells. The specific aims of the study were to investigate whether osteoprogenitor cells cultured on a rigorously cleaned implant specimen showed a normal pattern of differentiation and whether preadsorbed fibronectin accelerated or enhanced osteoblast differentiation. Materials and Methods Ti-6Al-4V disks were rigorously cleaned, passivated in nitric acid, and dry heat–sterilized; some of the disks were then coated with 1 nmol/L fibronectin. MC3T3 osteoprogenitor cells were then cultured on the pretreated disks for several weeks. Quantitative real-time polymerase chain reaction was performed to measure changes over time in the mRNA levels of osteoblast genes. Results Fibronectin increased the peak expression of all analyzed osteoblast gene markers. “Early” genes that normally mark the proliferative phase (0 to 10 days) of osteoblastic development showed peak expression within the first 10 days after cell attachment to the titanium alloy. In contrast, “late” genes that normally mark the differentiation (10 to 20 days) and mineralization (20 to 36 days) phases of osteoblastogenesis achieved peak expression only after approximately 3 to 4 weeks of culture. Conclusions Osteoprogenitors cultured on a rigorously cleaned Ti-6Al-4V alloy were found to demonstrate a normal pattern of osteoblast differentiation. Preadsorbed fibronectin was observed to stimulate osteoblast differentiation during the mineralization phase of osteoblastogenesis. PMID:23057020

Brown Adipose Tissue Function Is Enhanced in Long-Lived, Male Ames Dwarf Mice

PubMed Central

McFadden, Samuel; Fang, Yimin; Huber, Joshua A.; Zhang, Chi; Sun, Liou Y.; Bartke, Andrzej

2016-01-01

Ames dwarf mice (Prop1df/df) are long-lived due to a loss of function mutation, resulting in deficiency of GH, TSH, and prolactin. Along with a marked extension of longevity, Ames dwarf mice have improved energy metabolism as measured by an increase in their oxygen consumption and heat production, as well as a decrease in their respiratory quotient. Along with alterations in energy metabolism, Ames dwarf mice have a lower core body temperature. Moreover, Ames dwarf mice have functionally altered epididymal white adipose tissue (WAT) that improves, rather than impairs, their insulin sensitivity due to a shift from pro- to anti-inflammatory cytokine secretion. Given the unique phenotype of Ames dwarf epididymal WAT, their improved energy metabolism, and lower core body temperature, we hypothesized that Ames dwarf brown adipose tissue (BAT) may function differently from that of their normal littermates. Here we use histology and RT-PCR to demonstrate that Ames dwarf mice have enhanced BAT function. We also use interscapular BAT removal to demonstrate that BAT is necessary for Ames dwarf energy metabolism and thermogenesis, whereas it is less important for their normal littermates. Furthermore, we show that Ames dwarf mice are able to compensate for loss of interscapular BAT by using their WAT depots as an energy source. These findings demonstrate enhanced BAT function in animals with GH and thyroid hormone deficiencies, chronic reduction of body temperature, and remarkably extended longevity. PMID:27740871

Impairment of Natural Killer Cytotoxic Activity and Interferon γ Production in Ccaat/Enhancer Binding Protein γ–Deficient Mice

PubMed Central

Kaisho, Tsuneyasu; Tsutsui, Hiroko; Tanaka, Takashi; Tsujimura, Tohru; Takeda, Kiyoshi; Kawai, Taro; Yoshida, Nobuaki; Nakanishi, Kenji; Akira, Shizuo

1999-01-01

We have investigated in vivo roles of CCAAT/enhancer binding protein γ (C/EBPγ) by gene targeting. C/EBPγ-deficient (C/EBPγ2/−) mice showed a high mortality rate within 48 h after birth. To analyze the roles of C/EBPγ in lymphoid lineage cells, bone marrow chimeras were established. C/EBPγ2/− chimeras showed normal T and B cell development. However, cytolytic functions of their splenic natural killer (NK) cells after stimulation with cytokines such as interleukin (IL)-12, IL-18, and IL-2 were significantly reduced as compared with those of control chimera NK cells. In addition, the ability of C/EBPγ−/− chimera splenocytes to produce interferon (IFN)-γ in response to IL-12 and/or IL-18 was markedly impaired. NK cells could be generated in vitro with normal surface marker expression in the presence of IL-15 from C/EBPγ2/− newborn spleen cells. However, they also showed lower cytotoxic activity and IFN-γ production when stimulated with IL-12 plus IL-18 than control NK cells, as observed in C/EBPγ2/− chimera splenocytes. In conclusion, our study reveals that C/EBPγ is a critical transcription factor involved in the functional maturation of NK cells. PMID:10587348

In vivo competitive studies between normal and common gamma chain-defective bone marrow cells: implications for gene therapy.

PubMed

Otsu, M; Sugamura, K; Candotti, F

2000-09-20

Corrective gene transfer into hematopoietic stem cells (HSCs) is being investigated as therapy for X-linked severe combined immunodeficiency (XSCID) and it is hoped that selective advantage of gene-corrected HSCs will help in achieving full immune reconstitution after treatment. Lines of evidence from the results of allogeneic bone marrow transplantation in patients with XSCID support this hypothesis that, however, has not been rigorously tested in an experimental system. We studied the competition kinetics between normal and XSCID bone marrow (BM) cells using a murine bone marrow transplantation (BMT) model. For easy chimerism determination, we used genetic marking with retrovirus-mediated expression of the enhanced green fluorescent protein (EGFP). We found that XSCID BM cells were able to compete with normal BM cells for engraftment of myeloid lineages in a dose-dependent manner, whereas we observed selective repopulation of T, B, and NK cells deriving from normal BM cells. This was true despite the evidence of competitive engraftment of XSCID lineage marker-negative/c-Kit-positive (Lin-/c-Kit+) cells in the bone marrow of treated animals. From these results we extrapolate that genetic correction of XSCID HSCs will result in selective advantage of gene-corrected lymphoid lineages with consequent restoration of lymphocyte populations and high probability of clinical benefit.

Cerebral glucose deficiency versus oxygen deficiency in neonatal encephalopathy.

PubMed

Rudolph, A M

2018-04-24

Hypoxic-ischemic encephalopathy (HIE) in newborn infants is generally considered to result from decreased arterial oxygen content or cerebral blood flow. Cerebral injury similar to that of HIE has been noted with hypoglycemia. Studies in fetal lambs have shown that ventilation with 3% oxygen did not change cerebral blood flow, but ventilation with 100% oxygen resulted in marked reduction in cerebral blood flow, glucose delivery and glucose consumption. Blood glucose concentration falls markedly after birth; this, associated with the fall in cerebral blood flow, greatly reduces glucose supply to the brain. In preterm infants, blood glucose levels tend to be very low. Also persistent patency of the ductus arteriosus may reduce cerebral flow in diastole, thus exaggerating the decrease in glucose supply. I propose that glycopenic-ischemic encephalopathy is a more appropriate term for the cerebral insult. We should consider more aggressive management of the low blood glucose concentrations in the neonate, and particularly in preterm infants. Administration of high levels of oxygen in inspired air should be avoided to reduce the enhancement of cerebral vasoconstriction and decreased flow that normally occurs after birth.

Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab.

PubMed

Lassau, N; Coiffier, B; Kind, M; Vilgrain, V; Lacroix, J; Cuinet, M; Taieb, S; Aziza, R; Sarran, A; Labbe-Devilliers, C; Gallix, B; Lucidarme, O; Ptak, Y; Rocher, L; Caquot, L M; Chagnon, S; Marion, D; Luciani, A; Feutray, S; Uzan-Augui, J; Benatsou, B; Bonastre, J; Koscielny, S

2016-10-01

Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. 2007-A00399-44. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Claudin-4 Deficiency Results in Urothelial Hyperplasia and Lethal Hydronephrosis

PubMed Central

Fujita, Harumi; Hamazaki, Yoko; Noda, Yumi; Oshima, Masanobu; Minato, Nagahiro

2012-01-01

Claudin (Cld)-4 is one of the dominant Clds expressed in the kidney and urinary tract, including selective segments of renal nephrons and the entire urothelium from the pelvis to the bladder. We generated Cldn4 −/− mice and found that these mice had increased mortality due to hydronephrosis of relatively late onset. While the renal nephrons of Cldn4 −/− mice showed a concomitant diminution of Cld8 expression at tight junction (TJ), accumulation of Cld3 at TJ was markedly enhanced in compensation and the overall TJ structure was unaffected. Nonetheless, Cldn4 −/− mice showed slightly yet significantly increased fractional excretion of Ca2+ and Cl−, suggesting a role of Cld4 in the specific reabsorption of these ions via a paracellular route. Although the urine volume tended to be increased concordantly, Cldn4 −/− mice were capable of concentrating urine normally on dehydration, with no evidence of diabetes insipidus. In the urothelium, the formation of TJs and uroplaques as well as the gross barrier function were also unaffected. However, intravenous pyelography analysis indicated retarded urine flow prior to hydronephrosis. Histological examination revealed diffuse hyperplasia and a thickening of pelvic and ureteral urothelial layers with markedly increased BrdU uptake in vivo. These results suggest that progressive hydronephrosis in Cldn4 −/− mice arises from urinary tract obstruction due to urothelial hyperplasia, and that Cld4 plays an important role in maintaining the homeostatic integrity of normal urothelium. PMID:23284964

Clonidine prevents enhancement of spinal sympathetic transmission by phosphodiesterase inhibitors.

PubMed

Franz, D N; Madsen, P W

1982-02-12

Preganglionic sympathetic discharges, evoked by cervical stimulation in spinal cats, were rapidly and markedly enhanced for 1-2 h by aminophylline or isobutylmethylxanthine. Clonidine depressed intraspinal transmission and prevented enhancement by the xanthines; alpha 2-receptor antagonists blocked the effect of clonidine and not only restored but also markedly prolonged the enhancement by the xanthines. The results suggest that the excitability of sympathetic preganglionic neurons is regulated by cyclic AMP through activation of different subtypes of adrenergic receptors that are either positively or negatively coupled to adenylate cyclase.

Identification of Skin Electrical Injury Using Infrared Imaging: A Possible Complementary Tool for Histological Examination

PubMed Central

Lin, Hancheng; Wang, Zhenyuan; Dong, Hongmei

2017-01-01

In forensic practice, determination of electrocution as a cause of death usually depends on the conventional histological examination of electrical mark in the body skin, but the limitation of this method includes subjective bias by different forensic pathologists, especially for identifying suspicious electrical mark. The aim of our work is to introduce Fourier transform infrared (FTIR) spectroscopy in combination with chemometrics as a complementary tool for providing an relatively objective diagnosis. The results of principle component analysis (PCA) showed that there were significant differences of protein structural profile between electrical mark and normal skin in terms of α-helix, antiparallel β-sheet and β-sheet content. Then a partial least square (PLS) model was established based on this spectral dataset and used to discriminate electrical mark from normal skin areas in independent tissue sections as revealed by color-coded digital maps, making the visualization of electrical injury more intuitively. Our pilot study demonstrates the potential of FTIR spectroscopy as a complementary tool for diagnosis of electrical mark. PMID:28118398

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

Wolfe, R.R.; Peters, E.J.; Klein, S.

In this study the rate of lipolysis (fatty acid and glycerol release into blood) has been quantified in both normal weight and obese volunteers after both 15 and 87 h of fasting. In each study, the basal rate and subsequent response to epinephrine infusion were determined. The rate of appearance (R/sub a/) of free fatty acids (FFA) and glycerol were quantified by infusion of (1- TC)palmitate and D-5-glycerol, respectively. Substrate flux rates per unit of body fat mass and lean body mass were calculated from total body water measurements using H2 YO dilution. In normal volunteers, the basal R/sub a/more » FFA and R/sub a/ glycerol rose markedly with 87 h of fasting, whereas the increases were more modest in the obese subjects. However, the rate of mobilization of fat, in relation to the lean body mass, was higher in the obese subjects than in the normal subjects after 15 h of fasting, and the values were similar in both groups after 87 h of fasting. There was an increased lipolytic response to epinephrine after fasting in both groups. This increased sensitivity may have resulted from the enhancement of fatty acid-triglyceride substrate cycling that occurred after fasting.« less

Staining intraoperative topical solutions with fluorescein: enhancing the safety of sinus surgery.

PubMed

Yao, William C; Regone, Rachel M; Takashima, Masayoshi

2015-09-01

Oxymetazoline HCl 0.05%, 1:100,000 lidocaine with epinephrine (lido+epi), and 1:1000 epinephrine are all colorless solutions employed in sinus surgery. Because lido+epi is injected whereas others are not, care must be taken to label all solutions to avoid inadvertent injection of oxymetazoline or concentrated epinephrine because of life-threatening complications. Dyes have been used to color solutions for visual identification, but efficacy and cost have never been compared. We sought to determine the effectiveness of surgical marking pen (gentian violet) and fluorescein strips as coloring agents in mediums commonly used in sinus surgery. In this specialty techniques study, 4 liquid mediums (normal saline [NS], 0.05% oxymetazoline, 1:1,000 epinephrine, and lido+epi) and 2 coloring agents (fluorescein strip and surgical marking pen) were combined separately. Photos and absorbance of each solution were obtained at 15-minute intervals over 2 hours using a spectrophotometer. Peak absorbance remained stable for all solutions with fluorescein. Absorbance also remained constant for NS (0.37 absorbance units [AU] → 0.37 AU) and oxymetazoline (2.8 AU → 2.8 AU) mixed with marking pen. Absorbance decreased over 2 hours when marking pen was mixed with 1:1000 epinephrine (0.82 AU → 0.32 AU) and lido+epi (1.19 AU → 0.33 AU). Furthermore, the majority of color visibility and absorbance decreased in the first 15 minutes for concentrated epinephrine (0.82 → 0.33) and lido+epi (1.19 → 0.51). Cost of fluorescein strips ($0.14 to $0.20/strip) was less than marking pens ($13 to 46/pen). Compared to marking pen dye, solutions dyed with fluorescein retained their color and did not decay over time. We recommend fluorescein strips to label colorless materials in the operating room because of their lack of color decay and cost advantages. © 2015 ARS-AAOA, LLC.

Errors in radiographic interpretation made by veterinary students.

PubMed

Lamb, C R; Pfeiffer, D U; Mantis, P

2007-01-01

As a means of identifying student weaknesses in radiographic interpretation that could be used as foci for teaching, a cohort of 96 students joining the final-year radiology rotation were randomly allocated to one of three radiographic interpretation quizzes, each based on radiographs of small-animal patients together with the signalment and a brief, relevant history. Students' quiz scores were analyzed by multiple logistic regression, using an outcome variable with the score for each item as numerator and maximum possible mark as denominator. Students' median quiz score was 49% of the maximum (range 23-80%). Students were more likely to gain a mark for items based on abnormal radiographs than for those based on normal radiographs (odds ratio 3.4, p < 0.001). Skeletal radiographs were associated with lower scores (OR 0.75, p = 0.03). The fewest marks were awarded for interpretation of a radiograph of a normal canine stifle and interpretation of a radiograph of a normal canine pelvis; these items were misinterpreted as abnormal by 86% and 80% of the students, respectively. Students' tendency to over-interpret normal radiographs may reflect a lack of knowledge of radiographic anatomy or an unrealistically high expectation that the radiographs are abnormal.

The Use of Marking Rules in Semantic Systems. Working Papers of the Language Behavior Research Laboratory, No. 26.

ERIC Educational Resources Information Center

Geoghegan, William H.

This paper discusses the type of marking rule normally used in the production and interpretation of message forms for which semantic marking is possible. The structure and use of such rules is illustrated through a recent study of the semantics of personal address among the Balangingi' Samal, a Muslim group of the southern Philippines. The rule…

Gravity Plays an Important Role in Muscle Development and the Differentiation of Contractile Protein Phenotype

NASA Technical Reports Server (NTRS)

Adams, Gregory A.; Haddad, Fadia; Baldwin, Kenneth M.

2003-01-01

Several muscles in the body exist mainly to work against gravity. Whether gravity is important in the development of these muscles is not known. By examining the basic proteins that compose muscle, questions about the role of gravity in muscle development can be answered. Myosin heavy chains (MHCs) are a family of proteins critically important for muscle contraction. Several types of MHCs exist (e.g., neonatal, slow, fast), and each type is produced by a particular gene. Neonatal MHCs are produced early in life. Slow MHCs are important in antigravity muscles, and fast MHCs are found in fast-twitch power muscles. The gene that is turned on or expressed will determine which MHC is produced. Early in development, antigravity skeletal muscles (muscles that work against gravity) normally produce a combination of the neonatal/embryonic MHCs. The expression of these primitive MHCs is repressed early in development; and the adult slow and fast MHC genes become fully expressed. We tested the hypothesis that weightbearing activity is critical for inducing the normal expression of the slow MHC gene typically expressed in adult antigravity muscles. Also, we hypothesized that thyroid hormone, but not opposition to gravity, is necessary for expressing the adult fast IIb MHC gene essential for high-intensity muscle performance. Groups of normal thyroid and thyroid-deficient neonatal rats were studied after their return from the 16-day Neurolab mission and compared to matched controls. The results suggest: (1) Weightlessness impaired body and limb skeletal muscle growth in both normal and thyroid-deficient animals. Antigravity muscles were impaired more than those used primarily for locomotion andor nonweightbearing activity. (2) Systemic and muscle expression of insulin-like growth factor-I (IGF-I), an important body and tissue growth factor, was depressed in flight animals. (3) Normal slow, type I MHC gene expression was markedly repressed in the normal thyroid flight group. (4) Fast IIb MHC gene expression was enhanced in fast-twitch muscles of normal thyroid animals exposed to spaceflight; however, thyroid deficiency markedly repressed expression of this gene independently of spaceflight. In summary, the absence of gravity, when imposed at critical stages of development, impaired body and skeletal muscle growth, as well as expression of the MHC gene family of motor proteins. This suggests that normal weightbearing activity is essential for establishing body and muscle growth in neonatal animals, and for expressing the motor gene essential for supporting antigravity functions.

A Closer Look at Solar Wind Sputtering of Lunar Surface Materials

NASA Technical Reports Server (NTRS)

Barghouty, A. F.; Adams, J. H., Jr.; Meyer, F.; Mansur, L.; Reinhold, C.

2008-01-01

Solar-wind induced potential sputtering of the lunar surface may be a more efficient erosive mechanism than the "standard" kinetic (or physical) sputtering. This is partly based on new but limited laboratory measurements which show marked enhancements in the sputter yields of slow-moving, highly-charged ions impacting oxides. The enhancements seen in the laboratory can be orders of magnitude for some surfaces and highly charged incident ions, but seem to depend very sensitively on the properties of the impacted surface in addition to the fluence, energy and charge of the impacting ion. For oxides, potential sputtering yields are markedly enhanced and sputtered species, especially hydrogen and light ions, show marked dependence on both charge and dose.

Decursin enhances TRAIL‐induced apoptosis through oxidative stress mediated‐ endoplasmic reticulum stress signalling in non‐small cell lung cancers

PubMed Central

Kim, Jaekwang; Yun, Miyong; Kim, Eun‐Ok; Jung, Deok‐Beom; Won, Gunho; Kim, Bonglee; Jung, Ji Hoon

2016-01-01

Background and Purpose The TNF‐related apoptosis‐inducing ligand (TRAIL) is a promising anticancer agent due to its remarkable ability to selectively kill tumour cells. However, because most tumours exhibit resistance to TRAIL‐induced apoptosis, the development of combination therapies to overcome resistance to TRAIL is required for effective cancer therapy. Experimental Approach Cell viability and possible synergy between the plant pyranocoumarin decursin and TRAIL was measured by MTT assay and calcusyn software. Reactive oxygen species (ROS) and apoptosis were measured using dichlorodihydrofluorescein and annexin/propidium iodide in cell flow cytometry. Changes in protein levels were assessed with Western blotting. Key Results Combining decursin and TRAIL markedly decreased cell viability and increased apoptosis in TRAIL‐resistant non‐small‐cell lung cancer (NSCLC) cell lines. Decursin induced expression of the death receptor 5 (DR5). Inhibition of DR5 attenuated apoptotic cell death in decursin + TRAIL treated NSCLC cell lines. Interestingly, induction of DR5 and CCAAT/enhancer‐binding protein homologues protein by decursin was mediated through selective induction of the pancreatic endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) branch of the endoplasmic reticulum stress response pathway. Furthermore, enhancement of PERK/ATF4 signalling by decursin was mediated by ROS generation in NSCLC cell lines, but not in normal human lung cells. Decursin also markedly down‐regulated expression of survivin and Bcl‐xL in TRAIL‐resistant NSCLC cells. Conclusions and Implications ROS generation by decursin selectively activated the PERK/ATF4 axis of the endoplasmic reticulum stress signalling pathway, leading to enhanced TRAIL sensitivity in TRAIL‐resistant NSCLC cell lines, partly via up‐regulation of DR5. PMID:26661339

Evaluation of retroreflective markings to increase rail car conspicuity

DOT National Transportation Integrated Search

1998-10-01

The purpose of this study was to develop guidelines and recommendations for the design of retroreflective marking systems to enhance the conspicuity of rail cars at night. Three methods were used to generate and evaluate the marking systems for a sta...

A mathematical and experimental simulation of the hematological response to weightlessness

NASA Technical Reports Server (NTRS)

Kimzey, S. L.; Leonard, J. I.; Johnson, P. C.

1979-01-01

A mathematical model of erythropoiesis control was used to simulate the effects of bedrest and zero-g on the circulating red cell mass. The model incorporates the best current understanding of the dynamics of red cell production and destruction and the associated feedback regulation. Specifically studied were the hemodynamic responses of a 28-day bedrest study devised to simulate Skylab experience. The results support the hypothesis that red cell loss during supine bedrest is a normal physiological feedback process in response to hemoconcentration enhanced tissue oxygenation and suppression of red cell production. Model simulation suggested the possibilities that this period was marked by some combination of increased oxygen-hemoglobin affinity, small reduction in mean red cell life span, ineffective erythropoiesis, or abnormal reticulocytosis.

Monitoring Sunitinib-Induced Vascular Effects to Optimize Radiotherapy Combined with Soy Isoflavones in Murine Xenograft Tumor1

PubMed Central

Hillman, Gilda Gali; Singh-Gupta, Vinita; Al-Bashir, Areen K; Yunker, Christopher K; Joiner, Michael C; Sarkar, Fazlul H; Abrams, Judith; Haacke, E Mark

2011-01-01

Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to monitor vascular changes induced by sunitinib within a murine xenograft kidney tumor, we previously determined a dose that caused only partial destruction of blood vessels leading to “normalization” of tumor vasculature and improved blood flow. In the current study, kidney tumors were treated with this dose of sunitinib to modify the tumor microenvironment and enhance the effect of kidney tumor irradiation. The addition of soy isoflavones to this combined antiangiogenic and radiotherapy approach was investigated based on our studies demonstrating that soy isoflavones can potentiate the radiation effect on the tumors and act as antioxidants to protect normal tissues from treatment-induced toxicity. DCE-MRI was used to monitor vascular changes induced by sunitinib and schedule radiation when the uptake and washout of the contrast agent indicated regularization of blood flow. The combination of sunitinib with tumor irradiation and soy isoflavones significantly inhibited the growth and invasion of established kidney tumors and caused marked aberrations in the morphology of residual tumor cells. DCE-MRI studies demonstrated that the three modalities, sunitinib, radiation, and soy isoflavones, also exerted antiangiogenic effects resulting in increased uptake and clearance of the contrast agent. Interestingly, DCE-MRI and histologic observations of the normal contralateral kidneys suggest that soy could protect the vasculature of normal tissue from the adverse effects of sunitinib. An antiangiogenic approach that only partially destroys inefficient vessels could potentially increase the efficacy and delivery of cytotoxic therapies and radiotherapy for unresectable primary renal cell carcinoma tumors and metastatic disease. PMID:21461174

Exposure to a high-fat diet during development alters leptin and ghrelin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.

PubMed

Prior, Larissa J; Davern, Pamela J; Burke, Sandra L; Lim, Kyungjoon; Armitage, James A; Head, Geoffrey A

2014-02-01

Exposure to maternal obesity or a maternal diet rich in fat during development may have adverse outcomes in offspring, such as the development of obesity and hypertension. The present study examined the effect of a maternal high-fat diet (m-HFD) on offspring blood pressure and renal sympathetic nerve activity, responses to stress, and sensitivity to central administration of leptin and ghrelin. Offspring of New Zealand white rabbits fed a 13% HFD were slightly heavier than offspring from mothers fed a 4% maternal normal fat diet (P<0.05) but had 64% greater fat pad mass (P=0.015). Mean arterial pressure, heart rate, and renal sympathetic nerve activity at 4 months of age were 7%, 7%, and 24% greater, respectively (P<0.001), in m-HFD compared with maternal normal fat diet rabbits, and the renal sympathetic nerve activity response to airjet stress was enhanced in the m-HFD group. m-HFD offspring had markedly elevated pressor and renal sympathetic nerve activity responses to intracerebroventricular leptin (5-100 µg) and enhanced sympathetic responses to intracerebroventricular ghrelin (1-5 nmol). In contrast, there was resistance to the anorexic effects of intracerebroventricular leptin and less neuronal activation as detected by Fos immunohistochemistry in the arcuate (-57%; P<0.001) and paraventricular (-37%; P<0.05) nuclei of the hypothalamus in m-HFD offspring compared with maternal normal fat diet rabbits. We conclude that offspring from mothers consuming an HFD exhibit an adverse cardiovascular profile in adulthood because of altered central hypothalamic sensitivity to leptin and ghrelin.

Enhanced Depth SD-OCT Images Reveal Characteristic Choroidal Changes in Patients With Vogt-Koyanagi-Harada Disease.

PubMed

Li, Mei; Liu, Qiuhui; Luo, Yan; Li, Yonghao; Lin, Shaofen; Lian, Ping; Yang, Qiufen; Li, Xiaofang; Liu, Xialin; Sadda, SriniVas; Lu, Lin

2016-11-01

To identify characteristic choroidal changes of patients with Vogt-Koyanagi-Harada (VKH) disease at different stages. Fifty-four patients with VKH in the acute uveitic or convalescent stages, 24 patients with central serous chorioretinopathy (CSC), and 54 normal participants were enrolled in this prospective, observational study. Enhanced depth imaging spectral-domain optical coherence tomography scans were captured for all subjects to allow for comparison of choroidal morphological findings. Numerous round or oval hyperreflective profiles with hyporeflective cores, corresponding to choroidal vessels, were observed in the choroid of control participants and patients with CSC; whereas the numbers of these profiles were markedly decreased in the choroid of VKH patients in both the acute uveitic and convalescent stages. A reduction in vascular profiles in the choroid is observed in VKH and may aid in the differentiation with disorders such as CSC. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:1004-1012.]. Copyright 2016, SLACK Incorporated.

Wrinkles enhance the diffuse reflection from the dragonfly Rhyothemis resplendens

PubMed Central

Nixon, M. R.; Orr, A. G.; Vukusic, P.

2015-01-01

The dorsal surfaces of the hindwings of the dragonfly Rhyothemis resplendens (Odonata: Libellulidae) reflect a deep blue from the multilayer structure in its wing membrane. The layers within this structure are not flat, but distinctly ‘wrinkled’, with a thickness of several hundred nanometres and interwrinkle crest distances of 5 µm and greater. A comparison between the backscattered light from R. resplendens and a similar, but un-‘wrinkled’ multilayer in the damselfly Matronoides cyaneipennis (Odonata: Calopterygidae) shows that the angle over which incident light is backscattered is increased by the wrinkling in the R. resplendens structure. Whereas the reflection from the flat multilayer of M. cyaneipennis is effectively specular, the reflection from the wrinkled R. resplendens multilayer spans 1.47 steradians (equivalent to ±40° for all azimuthal angles). This property enhances the visibility of the static wing over a broader angle range than is normally associated with a smooth multilayer, thereby markedly increasing its conspicuousness. PMID:25540236

TU-H-CAMPUS-TeP3-01: Gold Nanoparticle-Enhanced Radiation Therapy in In Vitro A549 Lung Carcinoma: Studies in Both Traditional Monolayer and Three Dimensional Cell Culture Models

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

Oumano, M; University of Massachusetts Lowell, Lowell, MA; Ngwa, W

Purpose: To measure the increase in in vitro radiosensitivity for A549 lung carcinoma cells due to gold nanoparticle (GNP) radiation dose enhancement in both traditional monolayer and three dimensional (3D) cell culture models. Methods: A γH2AX immunofluorescence assay is performed on monolayer A549 cell culture and quantitatively analyzed to measure the increase in double strand breaks (DSBs) resulting from GNP dose enhancement. A clonogenic survival assay (CSA) is then performed on monolayer A549 cell culture to assess true viability after treatment. And lastly, another γH2AX assay is performed on 3D A549 multicellular nodules overlaid on a bed of growth factormore » reduced matrigel to measure dose response in a model that better recapitulates treatment response to actual tumors in vivo. Results: The first γH2AX assay performed on the monolayer cell culture shows a significant increase in DSBs due to GNP dose enhancement. The maximum average observed increase in normalized fluorescent intensity for monolayer cell culture is 171% for the 6Gy-treatment groups incubated in 0.556 mg Au/ml solution. The CSA performed on monolayer cell culture also shows considerable GNP dose enhancement. The maximum decrease in the normalized surviving fraction is 12% for the 4Gy-treatment group incubated in 0.556 mg Au/ml. And lastly, the GNP dose enhancement is confirmed to be mitigated in three dimensional cell culture models as compared to the traditional monolayer model. The maximum average observed dose enhancement for 3D cell culture is 19% for the 6Gy-treatment groups and incubated in 0.556 mg Au/ml. Conclusion: A marked increase in radiosensitivity is observed for A549 lung carcinoma cells when treated with GNPs plus radiation as opposed to radiation alone. Traditional monolayer cell culture also shows a much more pronounced radiation dose enhancement than 3D cell culture.« less

Reduction of ventricular size after shunting for normal pressure hydrocephalus related to CSF dynamics before shunting.

PubMed Central

Tans, J T; Poortvliet, D C

1988-01-01

Reduction of ventricular size was determined by repeated computed tomography in 30 adult patients shunted for normal pressure hydrocephalus (NPH) and related to the pressure-volume index (PVI) and resistance to outflow of cerebrospinal fluid (Rcsf) measured before shunting. Rapid and marked reduction of ventricular size (n = 10) was associated with a significantly lower PVI than slow and moderate to marked (n = 13) or minimal to mild reduction (n = 7). Otherwise no relationship could be found between the reduction of ventricular size and PVI or Rcsf. It is concluded that both rate and magnitude of reduction of ventricular size after shunting for NPH are extremely variable. High brain elasticity seems to be the best predictor of rapid and marked reduction. PMID:3379425

Identification and Comparison of the Polar Phospholipids in Normal and Dry Eye Rabbit Tears by MALDI-TOF Mass Spectrometry

PubMed Central

Ham, Bryan M.; Cole, Richard B.; Jacob, Jean T.

2008-01-01

Purpose To identify and compare the phosphorylated lipids in normal and dry eye rabbit tears using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Methods MALDI-TOF MS studies were performed on tear samples from normal and dry eyes of female New Zealand White rabbits. Experimental dry eye was induced by complete removal of the main and accessory lacrimal glands and nictitating membranes. A solid ionic crystal MALDI matrix of paranitroaniline and butyric acid was used to enhance the mass spectral responses of the phospholipids. In addition, a novel lipid isolation, preconcentration, and clean-up method using pipettes containing immobilized metal ion affinity chromatography (IMAC) medium was used. Results The polar phospholipids present in the normal and dry eye rabbit tears showed both similarities and differences. Species related to platelet-activating factor (PAF) and/or lysophosphatidylcholine (lyso-PC), phosphatidylcholine (PC), and sphingomyelin (SM) were found in both the normal and dry eye rabbit tears. However, the number of types and the concentrations of SM molecules were markedly greater in the dry eye tears than in the normal tears. In addition, phosphatidylserine (PS) species that were readily detectable in dry eye tears were not found in normal tears. Conclusions The combination of immobilized metal ion affinity chromatography and the solid ionic crystal matrix for MALDI enabled the detection and study of phosphorylated lipids in the tears. Specific differences between phospholipid levels in normal and dry eye tears were observable with this methodology. The appearance of various SM species only in the dry eye tears may provide markers for this disease state in the future. PMID:16877399

Cafestol overcomes ABT-737 resistance in Mcl-1-overexpressed renal carcinoma Caki cells through downregulation of Mcl-1 expression and upregulation of Bim expression.

PubMed

Woo, S M; Min, K-J; Seo, B R; Nam, J-O; Choi, K S; Yoo, Y H; Kwon, T K

2014-11-06

Although ABT-737, a small-molecule Bcl-2/Bcl-xL inhibitor, has recently emerged as a novel cancer therapeutic agent, ABT-737-induced apoptosis is often blocked in several types of cancer cells with elevated expression of Mcl-1. Cafestol, one of the major compounds in coffee beans, has been reported to have anti-carcinogenic activity and tumor cell growth-inhibitory activity, and we examined whether cafestol could overcome resistance against ABT-737 in Mcl-1-overexpressed human renal carcinoma Caki cells. ABT-737 alone had no effect on apoptosis, but cafestol markedly enhanced ABT-737-mediated apoptosis in Mcl-1-overexpressed Caki cells, human glioma U251MG cells, and human breast carcinoma MDA-MB231 cells. By contrast, co-treatment with ABT-737 and cafestol did not induce apoptosis in normal human skin fibroblast. Furthermore, combined treatment with cafestol and ABT-737 markedly reduced tumor growth compared with either drug alone in xenograft models. We found that cafestol inhibited Mcl-1 protein expression, which is important for ABT-737 resistance, through promotion of protein degradation. Moreover, cafestol increased Bim expression, and siRNA-mediated suppression of Bim expression reduced the apoptosis induced by cafestol plus ABT-737. Taken together, cafestol may be effectively used to enhance ABT-737 sensitivity in cancer therapy via downregulation of Mcl-1 expression and upregulation of Bim expression.

46 CFR 162.060-22 - Marking requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... effects of normal wear and tear and exposure to water, salt spray, direct sunlight, heat, cold, and any...: SPECIFICATIONS AND APPROVAL ENGINEERING EQUIPMENT Ballast Water Management Systems § 162.060-22 Marking requirements. (a) Each ballast water management system (BWMS) manufactured under Coast Guard approval must have...

46 CFR 162.060-22 - Marking requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... effects of normal wear and tear and exposure to water, salt spray, direct sunlight, heat, cold, and any...: SPECIFICATIONS AND APPROVAL ENGINEERING EQUIPMENT Ballast Water Management Systems § 162.060-22 Marking requirements. (a) Each ballast water management system (BWMS) manufactured under Coast Guard approval must have...

46 CFR 162.060-22 - Marking requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... effects of normal wear and tear and exposure to water, salt spray, direct sunlight, heat, cold, and any...: SPECIFICATIONS AND APPROVAL ENGINEERING EQUIPMENT Ballast Water Management Systems § 162.060-22 Marking requirements. (a) Each ballast water management system (BWMS) manufactured under Coast Guard approval must have...

Targeting Alertness to Improve Cognition in Older Adults: A Preliminary Report of Benefits in Executive Function and Skill Acquisition

PubMed Central

Van Vleet, Thomas M.; DeGutis, Joseph M.; Merzenich, Michael M.; Simpson, Gregory V.; Zomet, Ativ; Dabit, Sawsan

2016-01-01

Efficient self-regulation of alertness declines with age exacerbating normal declines in performance across multiple cognitive domains, including learning and skill acquisition. Previous cognitive intervention studies have shown that it is possible to enhance alertness in patients with acquired brain injury and marked attention impairments, and that this benefit generalizes to improvements in more global cognitive functions. In the current preliminary studies, we sought to test whether this approach, that targets both tonic (over a period of minutes) and phasic (moment-to-moment) alertness, can improve key executive functioning declines in older adults, and enhance the rate of skill acquisition. The results of both experiments 1 and 2 demonstrate that, compared to active control training, alertness training significantly enhanced performance in several validated executive function measures. In experiment 2, alertness training significantly improved skill acquisition compared to active control training in a well-characterized speed of processing task, with the largest benefits shown in the most challenging speed of processing blocks. The results of the current study suggest that targeting intrinsic alertness in cognitive training provides a novel approach to improve executive functions in older adults and may be a useful adjunct treatment to enhance benefits gained in other clinically validated treatments. PMID:27372902

Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters.

PubMed

Kumar, Vibhor; Rayan, Nirmala Arul; Muratani, Masafumi; Lim, Stefan; Elanggovan, Bavani; Xin, Lixia; Lu, Tess; Makhija, Harshyaa; Poschmann, Jeremie; Lufkin, Thomas; Ng, Huck Hui; Prabhakar, Shyam

2016-05-01

Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation. © 2016 Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters

PubMed Central

Kumar, Vibhor; Rayan, Nirmala Arul; Muratani, Masafumi; Lim, Stefan; Elanggovan, Bavani; Xin, Lixia; Lu, Tess; Makhija, Harshyaa; Poschmann, Jeremie; Lufkin, Thomas; Ng, Huck Hui; Prabhakar, Shyam

2016-01-01

Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation. PMID:26957309

Growth hormone receptor deficiency (Laron syndrome): clinical and genetic characteristics.

PubMed

Guevara-Aguirre, J; Rosenbloom, A L; Vaccarello, M A; Fielder, P J; de la Vega, A; Diamond, F B; Rosenfeld, R G

1991-01-01

Approximately 60 cases of GHRD (Laron syndrome) were reported before 1990 and half of these were from Israel. We have described 47 additional patients from an inbred population of South Ecuador and have emphasized certain clinical features including: markedly advanced osseous maturation for height age; normal body proportions in childhood but child-like proportions in adults; much greater deviation of stature than head size, giving an appearance of large cranium and small facies; underweight in childhood despite the appearance of obesity and true obesity in adulthood; blue scleras; and limited elbow extension. The Ecuadorean patients differed markedly and most importantly from the other large concentration, in Israel, by being of normal or superior intelligence, suggesting a unique linkage in the Ecuadorean population. The Ecuadorean population also differed in that those patients coming from Loja province had a markedly skewed sex ratio (19 females: 2 males), while those from El Oro province had a normal sex distribution (14 females: 12 males). The phenotypic similarity between the El Oro and Loja patients indicates that this abnormal sex distribution is not a direct result of the GHRD.

Pretargeting CD45 enhances the selective delivery of radiation to hematolymphoid tissues in nonhuman primates

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

Green, Damian J.; Pagel, John M.; Nemecek, Eneida R.

2009-08-06

Pretargeted radioimmunotherapy (PRIT) is designed to enhance the directed delivery of radionuclides to malignant cells. Through a series of studies in nineteen nonhuman primates (M. fascicularis) the potential therapeutic advantage of anti-CD45 PRIT was evaluated. Anti-CD45 PRIT demonstrated a significant improvement in target-to-normal organ ratios of absorbed radiation when compared to directly radiolabeled bivalent antibody (conventional radioimmunotherapy [RIT]). Radio-DOTA-biotin administered 48 hours after anti-CD45 streptavidin fusion protein (FP) [BC8 (scFv)4SA] produced markedly lower concentrations of radiation in non-target tissues when compared to conventional RIT. PRIT generated superior target:normal organ ratios in the blood, lung and liver (10.3:1, 18.9:1 and 9.9:1more » respectively) when compared to the conventional RIT controls (2.6:1, 6.4:1 and 2.9:1 respectively). The FP demonstrated superior retention in target tissues relative to comparable directly radiolabeled bivalent anti-CD45 RIT. The time-point of administration of the second step radiolabeled ligand (radio-DOTA-biotin) significantly impacted the biodistribution of radioactivity in target tissues. Rapid clearance of the FP from the circulation rendered unnecessary the addition of a synthetic clearing agent in this model. These results support proceeding to anti-CD45 PRIT clinical trials for patients with both leukemia and lymphoma.« less

Trace elements in sera from patients with renal disease

NASA Astrophysics Data System (ADS)

Miura, Yoshinori; Nakai, Keiko; Sera, Kouichiro; Sato, Michirou

1999-04-01

In hemodialysis (HD) patients, an accumulation of trace elements such as aluminum, copper, silicon and vanadium has been reported. Aluminum-caused encephalopathy and aluminum-related bone diseases are important trace element-related complications. Using particle induced X-ray emission (PIXE) we determined concentrations of aluminum, silicon, copper, zinc, selenium and bromine in sera of 29 patients with HD, 14 nondialysis patients with renal disease (RD) and 27 normal controls. The concentration of serum silicon of the patients with HD was 107.4 ± 61.3 μmol/l, which is markedly higher than that of normal controls (48.3 ± 25.8 μmol/l, p < 0.0001). The serum concentrations of zinc and bromine in patients with HD were 11.9 ± 1.7 and 21.3 ± 3.0 μmol/l, respectively. Both were markedly lower than those of normal controls (15.6 ± 2.6, 69.2 ± 8.3 μmol/l, p < 0.0001). The concentrations of aluminium and bromine in the serum of patients with RD were 171.9 ± 64.3 and 81.9 ± 11.6 μmol/l, which were markedly higher than those of normal controls ( p < 0.0001, p < 0.001). No significant differences were observed in the concentration of copper and selenium among three groups.

Photodynamic therapy affects the expression of IL-6 and IL-10 in vivo

NASA Astrophysics Data System (ADS)

Gollnick, Sandra O.; Musser, David A.; Henderson, Barbara W.

1998-05-01

Photodynamic therapy (PDT), which can effectively destroy malignant tissue, also induces a complex immune response which potentiates anti-tumor immunity, but also inhibits skin contact hypersensitivity (CHS) and prolongs skin graft survival. The underlying mechanisms responsible for these effects are poorly understood, but are likely to involve meditation by cytokines. We demonstrate in a BALB/c mouse model that PDT delivered to normal and tumor tissue in vivo causes marked changes in the expression of cytokines interleukin (IL)-6 and IL-10. IL-6 mRNA and protein are rapidly and strongly enhanced in the PDT treated EMT6 tumor. Previous studies have shown that intratumoral injection of IL- 6 or transduction of the IL-6 gene into tumor cells can enhance tumor immunogenicity and inhibit tumor growth in experimental murine tumor systems. Thus, PDT may enhance local anti-tumor immunity by up-regulating IL-6. PDT also results in an increase in IL-10 mRNA and protein in the skin. The same PDT regime which enhances IL-10 production in the skin has been shown to strongly inhibit the CHS response. The kinetics of IL-10 expression coincide with the known kinetics of PDT induced CHS suppression and we propose that the enhanced IL-10 expression plays a role in the observed suppression of cell mediated responses seen following PDT.

Frequency of underweight and stunting among children entering school in a small urban locality and their association with academic performance.

PubMed

Ahmad, Mirza Sultan; Husain Zaidi, Syed Aizaz; Medhat, Naila; Farooq, Hadia; Ahmad, Danial; Nasir, Waqar

2018-01-01

To determine the frequency of underweight and stunting among the children entering first year of school and to assess its associated factors. This descriptive, analytical study was conducted at 5 schools of Rabwah, Pakistan, from August to September 2015, and comprised all students who got admission in the selected schools during the study period. Name, father's name, gender, weight, height, status of height, and weight on Z-score charts, and marks obtained in the test were recorded. SPSS 20 was used for statistical analysis. Of the 478 participants, 212(44.4%) were boys and 266(55.6%) were girls. The overall mean age was 66.6±5.966 months (range: 41-129 months). Overall, 53(11.1%) were underweight, 22(4.6%) were severely underweight, 55(11.5%) had stunting and 12(2.5%) had severe stunting. Median marks (Interquartile Range [IQR]) in admission test for obese, overweight, normal, underweight and severely underweight children were 76.3%(37.2-84.7), 65.9%, 66.7%(56.4-72.3), 64.6%(47-71), and 67%(55.3-78), respectively. Median marks (IQR) in admission test for tall, normal height, stunted and severe stunted children were 24.1%, 67%(57.3-73), 57%(31.1-67.8), and 62.6%(49.7-68.3), respectively. Children with stunting scored significantly fewer marks compared to children of normal height (p<0.05). Stunting and underweight were common problems among children starting school. Stunting was found to be associated with lower marks in admission test.

The prodomain of BMP4 is necessary and sufficient to generate stable BMP4/7 heterodimers with enhanced bioactivity in vivo.

PubMed

Neugebauer, Judith M; Kwon, Sunjong; Kim, Hyung-Seok; Donley, Nathan; Tilak, Anup; Sopory, Shailaja; Christian, Jan L

2015-05-05

Bone morphogenetic proteins 4 and 7 (BMP4 and BMP7) are morphogens that signal as either homodimers or heterodimers to regulate embryonic development and adult homeostasis. BMP4/7 heterodimers exhibit markedly higher signaling activity than either homodimer, but the mechanism underlying the enhanced activity is unknown. BMPs are synthesized as inactive precursors that dimerize and are then cleaved to generate both the bioactive ligand and prodomain fragments, which lack signaling activity. Our study reveals a previously unknown requirement for the BMP4 prodomain in promoting heterodimer activity. We show that BMP4 and BMP7 precursor proteins preferentially or exclusively form heterodimers when coexpressed in vivo. In addition, we show that the BMP4 prodomain is both necessary and sufficient for generation of stable heterodimeric ligands with enhanced activity and can enable homodimers to signal in a context in which they normally lack activity. Our results suggest that intrinsic properties of the BMP4 prodomain contribute to the relative bioactivities of homodimers versus heterodimers in vivo. These findings have clinical implications for the use of BMPs as regenerative agents for the treatment of bone injury and disease.

Infrared chemiluminescence study of the reaction Cl + HI yielding HCl + I at enhanced collision energies.

NASA Technical Reports Server (NTRS)

Cowley, L. T.; Horne, D. S.; Polanyi, J. C.

1971-01-01

Performed chemiluminescence and beam experiments show a markedly increased efficiency of conversion of the reaction energy into vibration and a markedly enhanced tendency for forward scattering in the reaction Cl + HI yields HCl + I as compared with H + Cl2 yields HCl + Cl. These differences appear to be due predominantly to the difference in the masses involved.

Immunochemical study of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria.

PubMed Central

Fujita, H; Sassa, S; Toback, A C; Kappas, A

1987-01-01

Hepatoerythropoietic porphyria (HEP) is due to a marked deficiency of uroporphyrinogen (URO) decarboxylase, a cytosolic enzyme in the heme biosynthetic pathway. Using a radioimmunoassay method, we determined the concentration of URO decarboxylase protein in erythrocytes from a patient with mild HEP and found that the enzyme protein concentration had markedly decreased to less than 7% of the normal controls. This finding, however, was in contrast to the enzyme activity in the patient's erythrocytes, which was 16% of normal control levels and different from previously reported HEP cases in that erythrocytes in our patient contained disproportionately elevated URO decarboxylase activity in comparison to its immunoreactive material. Our findings suggests the possibility of a mutant isozyme in this patient that is not immunoreactive with an antibody raised against the normal enzyme. PMID:3571497

Regional Cerebral Blood Flow Analysis in Patients with Multiple Sclerosis Using TC-99M Hmpao and a Three - Spect System.

NASA Astrophysics Data System (ADS)

D'Souza, Maximian Felix

1995-01-01

The purpose of the present study was to determine the changes in regional cerebral blood flow (rCBF) with a cognitive task of semantic word retrieval (verbal fluency) in patients with multiple sclerosis (MS) and compare with the rCBF distribution of normal controls. Two groups of patients with low and high verbal fluency scores and two groups of normal controls were selected to determine a relationship between rCBF and verbal performance. A three-detector gamma camera (TRIAD 88) was used with radiotracer Tc-99m HMPAO and single photon emission computed tomography (SPECT) to obtain 3D rCBF maps. The performance characteristics of the camera was comprehensively studied before being utilized for clinical studies. In addition, technical improvements were implemented in the form of scatter correction and MRI-SPECT coregistration to potentially enhance the quantitative accuracy of the rCBF data. The performance analysis of the gamma camera showed remarkable consistency among the three-detector heads and yielded results that were consistent with the manufacturer's specification. Measurements of physical objects also showed excellent image quality. The coregistration of SPECT and MRI images allowed more accurate anatomical localization for extraction of regional blood flow information. The validation of the scatter correction technique with physical phantoms indicated marked improvements in quantitative accuracy. There was marked difference in activation patterns between patients and normals. In normals, individually subjects showed either an increase or a decrease in blood flow to left frontal and temporal, however, on average, there was not a statistically significant change. The lack of significant change may suggest large variability among subjects chosen or that the individual changes are not large enough to be significant. The results from MS patients showed several left cortical areas with statistically significant change in blood flow after cognitive activation, especially in the low fluent group, with decreased flow. Scatter corrected data yielded mostly right sided significant increases in blood flow. Further studies must be conducted to further evaluate the scatter correction technique. Additional studies on MS patients must focus on correlating lesion volume, location and number to the rCBF distribution.

Multi-Disciplinary Peer-Mark Moderation of Group Work

ERIC Educational Resources Information Center

Willmot, Peter; Pond, Keith

2012-01-01

Self and peer assessment offers benefits for enhancing student learning. Peer moderation provides a convenient solution for awarding individual marks in group assignments. This paper provides a significant review of peer-mark moderation, and describes an award winning, web-based tool that was developed in the UK and is now spreading across the…

IGF-1 Restores Visual Cortex Plasticity in Adult Life by Reducing Local GABA Levels

PubMed Central

Maya-Vetencourt, José Fernando; Baroncelli, Laura; Viegi, Alessandro; Tiraboschi, Ettore; Castren, Eero; Cattaneo, Antonino; Maffei, Lamberto

2012-01-01

The central nervous system architecture is markedly modified by sensory experience during early life, but a decline of plasticity occurs with age. Recent studies have challenged this dogma providing evidence that both pharmacological treatments and paradigms based on the manipulation of environmental stimulation levels can be successfully employed as strategies for enhancing plasticity in the adult nervous system. Insulin-like growth factor 1 (IGF-1) is a peptide implicated in prenatal and postnatal phases of brain development such as neurogenesis, neuronal differentiation, synaptogenesis, and experience-dependent plasticity. Here, using the visual system as a paradigmatic model, we report that IGF-1 reactivates neural plasticity in the adult brain. Exogenous administration of IGF-1 in the adult visual cortex, indeed, restores the susceptibility of cortical neurons to monocular deprivation and promotes the recovery of normal visual functions in adult amblyopic animals. These effects were accompanied by a marked reduction of intracortical GABA levels. Moreover, we show that a transitory increase of IGF-1 expression is associated to the plasticity reinstatement induced by environmental enrichment (EE) and that blocking IGF-1 action by means of the IGF-1 receptor antagonist JB1 prevents EE effects on plasticity processes. PMID:22720172

The role of DNA methylation in directing the functional organization of the cancer epigenome.

PubMed

Lay, Fides D; Liu, Yaping; Kelly, Theresa K; Witt, Heather; Farnham, Peggy J; Jones, Peter A; Berman, Benjamin P

2015-04-01

The holistic role of DNA methylation in the organization of the cancer epigenome is not well understood. Here we perform a comprehensive, high-resolution analysis of chromatin structure to compare the landscapes of HCT116 colon cancer cells and a DNA methylation-deficient derivative. The NOMe-seq accessibility assay unexpectedly revealed symmetrical and transcription-independent nucleosomal phasing across active, poised, and inactive genomic elements. DNA methylation abolished this phasing primarily at enhancers and CpG island (CGI) promoters, with little effect on insulators and non-CGI promoters. Abolishment of DNA methylation led to the context-specific reestablishment of the poised and active states of normal colon cells, which were marked in methylation-deficient cells by distinct H3K27 modifications and the presence of either well-phased nucleosomes or nucleosome-depleted regions, respectively. At higher-order genomic scales, we found that long, H3K9me3-marked domains had lower accessibility, consistent with a more compact chromatin structure. Taken together, our results demonstrate the nuanced and context-dependent role of DNA methylation in the functional, multiscale organization of cancer epigenomes. © 2015 Lay et al.; Published by Cold Spring Harbor Laboratory Press.

Exercise Recommendations for the Management of Symptoms Clusters Resulting from Cancer and Cancer Treatments

PubMed Central

Mustian, Karen M.; Cole, Calvin L.; Lin, Po Ju; Asare, Matt; Fung, Chunkit; Janelsins, Michelle C.; Kamen, Charles S.; Peppone, Luke J.; Magnuson, Allison

2017-01-01

Objective To review existing exercise guidelines for cancer patients and survivors for the management of symptom clusters. Data source Review of Pubmed literature and published exercise guidelines. Conclusion Cancer and its treatments are responsible for a copious number of incapacitating symptoms that markedly impair quality of life (QOL). The exercise oncology literature provides consistent support for the safety and efficacy of exercise interventions in managing cancer- and treatment-related symptoms as well as improving quality of life in cancer patients and survivors. Implications for Nursing Practice Effective management of symptoms enhances recovery, resumption of normal life activities and QOL for patients and survivors. Exercise is a safe, appropriate and effective therapeutic option before, during, and after the completion of treatment for alleviating symptoms and symptom clusters. PMID:27776835

Mrc1 Marks Early-Firing Origins and Coordinates Timing and Efficiency of Initiation in Fission Yeast ▿ †

PubMed Central

Hayano, Motoshi; Kanoh, Yutaka; Matsumoto, Seiji; Masai, Hisao

2011-01-01

How early- and late-firing origins are selected on eukaryotic chromosomes is largely unknown. Here, we show that Mrc1, a conserved factor required for stabilization of stalled replication forks, selectively binds to the early-firing origins in a manner independent of Cdc45 and Hsk1 kinase in the fission yeast Schizosaccharomyces pombe. In mrc1Δ cells (and in swi1Δ cells to some extent), efficiency of firing is stimulated, and its timing is advanced selectively at those origins that are normally bound by Mrc1. In contrast, the late or inefficient origins which are not bound by Mrc1 are not activated in mrc1Δ cells. The enhanced firing and precocious Cdc45 loading at Mrc1-bound early-firing origins are not observed in a checkpoint mutant of mrc1, suggesting that non-checkpoint function is involved in maintaining the normal program of early-firing origins. We propose that prefiring binding of Mrc1 is an important marker of early-firing origins which are precociously activated by the absence of this protein. PMID:21518960

P-selectin deficiency attenuates tumor growth and metastasis

PubMed Central

Kim, Young J.; Borsig, Lubor; Varki, Nissi M.; Varki, Ajit

1998-01-01

Selectins are adhesion receptors that normally recognize certain vascular mucin-type glycoproteins bearing the carbohydrate structure sialyl-Lewisx. The clinical prognosis and metastatic progression of many epithelial carcinomas has been correlated independently with production of tumor mucins and with enhanced expression of sialyl-Lewisx. Metastasis is thought to involve the formation of tumor-platelet-leukocyte emboli and their interactions with the endothelium of distant organs. We provide a link between these observations by showing that P-selectin, which normally binds leukocyte ligands, can promote tumor growth and facilitate the metastatic seeding of a mucin-producing carcinoma. P-selectin-deficient mice showed significantly slower growth of subcutaneously implanted human colon carcinoma cells and generated fewer lung metastases from intravenously injected cells. Three potential pathophysiological mechanisms are demonstrated: first, intravenously injected tumor cells home to the lungs of P-selectin deficient mice at a lower rate; second, P-selectin-deficient mouse platelets fail to adhere to tumor cell-surface mucins; and third, tumor cells lodged in lung vasculature after intravenous injection often are decorated with platelet clumps, and these are markedly diminished in P-selectin-deficient animals. PMID:9689079

Enhancing Soundtracks From Old Movies

NASA Technical Reports Server (NTRS)

Frazer, Robert E.

1992-01-01

Proposed system enhances soundtracks of old movies. Signal on optical soundtrack of film digitized and processed to reduce noise and improve quality; timing signals added, and signal recorded on compact disk. Digital comparator and voltage-controlled oscillator synchronizes speed of film-drive motor and compact disk motor. Frame-coded detector reads binary frame-identifying marks on film. Digital comparator generates error signal if marks on film do not match those on compact disk.

Combined treatment with D-allose, docetaxel and radiation inhibits the tumor growth in an in vivo model of head and neck cancer

PubMed Central

Hoshikawa, Hiroshi; Kamitori, Kazuyo; Indo, Kanako; Mori, Terushige; Kamata, Mizuna; Takahashi, Tomoko; Tokuda, Masaaki

2018-01-01

The present study was designed to evaluate the effect of one rare sugar, D-allose, on normal human cells and cutaneous tissue, and to investigate the radiosensitizing and chemosensitizing potential of D-allose in an in vivo model of head and neck cancer. Results indicated that D-allose did not inhibit the growth of normal human fibroblasts TIG-1 cells, and no apoptotic changes were observed after D-allose and D-glucose treatment. The mRNA expression levels of thioredoxin interacting protein (TXNIP) in TIG-1 cells after D-allose treatment increased by 2-fold (50.4 to 106.5). Conversely, the mRNA expression levels of TXNIP in HSC3 cancer cells increased by 74-fold (1.5 to 110.6), and the thioredoxin (TRX)/TXNIP ratio was markedly reduced from 61.7 to 1.4 following D-allose treatment. Combined multiple treatments with docetaxel, radiation and D-allose resulted in the greatest antitumor response in the in vivo model. Hyperkeratosis, epidermal thickening and tumor necrosis factor-α immunostaining were observed following irradiation treatment, but these pathophysiological reactions were reduced following D-allose administration. Thus, the present findings suggest that D-allose may enhance the antitumor effects of chemoradiotherapy whilst sparing normal tissues. PMID:29456721

Performance of Junctional Tourniquets in Normal Human Volunteers

DTIC Science & Technology

2014-12-01

cross-hatch marks, and the left side was the zero point that anchored the line. The subject made a cross mark on the line, which went from the left...the ankle . The AAJT, which aims to compress the distal aorta and adjacent blood vessels when used over the umbilicus where there appears to be no

Subcategory learning in normal and language learning-disabled adults: how much information do they need?

PubMed

Richardson, Jessica; Harris, Laurel; Plante, Elena; Gerken, Louann

2006-12-01

The purpose of this experiment was to determine if nonreferential morphophonological information was sufficient to facilitate the learning of gender subcategories (i.e., masculine vs. feminine) in individuals with normal language (NL) and those with a history of language-based learning disabilities (HLD). Thirty-two adults listened for 18 min to a familiarization set of Russian words that included either 1 (single-marked) or 2 (double-marked) morphophonological markers indicating gender. Participants were then tested on their knowledge of both trained and untrained members of each gender subcategory. Testing indicated that morphophonological information is sufficient for lexical subcategory learning in both NL and HLD groups, although the HLD group had lower overall accuracy. The HLD group benefited from double-marking relative to single-marking for subcategory learning. The results demonstrated that learning through implicit mechanisms occurred after a relatively brief exposure to the language stimuli. In addition, the weaker overall learning by the HLD group was facilitated when multiple cues to linguistic subcategory were available in the input group members received.

The enhancement mechanism of wine-processed Radix Scutellaria on NTG-induced migraine rats.

PubMed

Cui, Cheng-Long; He, Xin; Dong, Cui-Lan; Song, Zi-Jing; Ji, Jun; Wang, Xue; Wang, Ling; Wang, Jiao-Ying; Du, Wen-Juan; Wang, Chong-Zhi; Yuan, Chun-Su; Guo, Chang-Run; Zhang, Chun-Feng

2017-07-01

To elucidate the increasing dissolution and enhancement mechanism of wine-processed Radix Scutellaria (RS) by fractal theory in nitroglycerin (NTG)-induced migraine rats. We prepared three RS from the process with 10% (S1), 15% (S2), 20% (S3) (v/m) rice wine. Mercury intrusion porosimetry and scanning electron microscope were employed to explore the internal structure of RS and the components dissolution of RS was analyzed by HPLC. Rats were randomly allocated into following groups and orally given different solutions for 10days: normal group (NOR, normal saline), model group (MOD, normal saline), Tianshu capsule group (TSC, 0.425mg/kg), ibuprofen group (IBU, 0.0821mg/kg), crude RS group (CRU, 1.04mg/kg) and wine-processed RS group (WP, 1.04mg/kg) followed by bolus subcutaneously injection of NTG (10mg/kg) to induce migraine model except NOR. Biochemical indexes (nitric oxide-NO, calcitonin-gene-related peptide-CGRP, and endothelin-ET) and c-fos positive cells were measured with commercial kits and immunohistochemical method, separately. Total surface area significantly increased in wine-processed RS (p<0.05) while fractal dimension markedly decreased (p<0.05) compared with crude RS. Additionally, S3 owned the highest increase of dissolution including the percentage increase of total extract, total flavonoids and main compounds (all p<0.05 vs S1 and S2). Pharmacodynamic data showed c-fos positive cells significantly decreased (p<0.05) in WP compared with MOD and the level of NO, CGRP, ET in WP was better than that of CRU. Wine-processed RS could be a promising candidate medicine for migraine treatment due to its increased component dissolution. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Minimal RED cell pairs markedly improve electrode kinetics and power production in microbial reverse electrodialysis cells.

PubMed

Cusick, Roland D; Hatzell, Marta; Zhang, Fang; Logan, Bruce E

2013-12-17

Power production from microbial reverse electrodialysis cell (MRC) electrodes is substantially improved compared to microbial fuel cells (MFCs) by using ammonium bicarbonate (AmB) solutions in multiple RED cell pair stacks and the cathode chamber. Reducing the number of RED membranes pairs while maintaining enhanced electrode performance could help to reduce capital costs. We show here that using only a single RED cell pair (CP), created by operating the cathode in concentrated AmB, dramatically increased power production normalized to cathode area from both acetate (Acetate: from 0.9 to 3.1 W/m(2)-cat) and wastewater (WW: 0.3 to 1.7 W/m(2)), by reducing solution and charge transfer resistances at the cathode. A second RED cell pair increased RED stack potential and reduced anode charge transfer resistance, further increasing power production (Acetate: 4.2 W/m(2); WW: 1.9 W/m(2)). By maintaining near optimal electrode power production with fewer membranes, power densities normalized to total membrane area for the 1-CP (Acetate: 3.1 W/m(2)-mem; WW: 1.7 W/m(2)) and 2-CP (Acetate: 1.3 W/m(2)-mem; WW: 0.6 W/m(2)) reactors were much higher than previous MRCs (0.3-0.5 W/m(2)-mem with acetate). While operating at peak power, the rate of wastewater COD removal, normalized to reactor volume, was 30-50 times higher in 1-CP and 2-CP MRCs than that in a single chamber MFC. These findings show that even a single cell pair AmB RED stack can significantly enhance electrical power production and wastewater treatment.

Prominent subcutaneous oedema as a masquerading symptom of an underlying inflammatory myopathy.

PubMed

Anantharajah, Anthea; Vucic, Steve; Tarafdar, Surjit; Vongsuvanh, Roslyn; Wilcken, Nicholas; Swaminathan, Sanjay

2017-02-01

The inflammatory myopathies are a group of immune-mediated inflammatory muscle disorders that typically present with marked proximal muscle weakness. We report four cases of inflammatory myopathies with marked subcutaneous oedema as their main complaint. Three of the four patients had normal or low levels of creatine kinase, an enzyme often markedly elevated in these disorders. Magnetic resonance imaging of the muscles, followed by a muscle biopsy were used to make a definitive diagnosis. © 2017 Royal Australasian College of Physicians.

Nitric oxide alleviates oxidative damage induced by enhanced ultraviolet-B radiation in cyanobacterium.

PubMed

Xue, Lingui; Li, Shiweng; Sheng, Hongmei; Feng, Huyuan; Xu, Shijian; An, Lizhe

2007-10-01

To study the role of nitric oxide (NO) on enhanced ultraviolet-B (UV-B) radiation (280-320 nm)-induced damage of Cyanobacterium, the growth, pigment content, and antioxidative activity of Spirulina platensis-794 cells were investigated under enhanced UV-B radiation and under different chemical treatments with or without UV-B radiation for 6 h. The changes in chlorophyll-a, malondialdehyde content, and biomass confirmed that 0.5 mM: sodium nitroprusside (SNP), a donor of nitric oxide (NO), could markedly alleviate the damage caused by enhanced UV-B. Specifically, the biomass and the chlorophyll-a content in S. platensis-794 cells decreased 40% and 42%, respectively under enhanced UV-B stress alone, but they only decreased 10% and 18% in the cells treated with UV-B irradiation and 0.5 mM: SNP. Further experiments suggested that NO treatment significantly increased the activities of superoxide dismutase (SOD) and catalase (CAT), and decreased the accumulation of O (2)(-) in enhanced UV-B-irradiated cells. SOD and CAT activity increased 0.95- and 6.73-fold, respectively. The accumulation of reduced glutathione (GSH) increased during treatment with 0.5 mM: SNP in normal S. platensis cells, but SNP treatment could inhibit the increase of GSH in enhanced UV-B-stressed S. platensis cells. Thus, these results suggest that NO can strongly alleviate oxidative damage caused by UV-B stress by increasing the activities of SOD, peroxidase, CAT, and the accumulation of GSH, and by eliminating O (2)(-) in S. platensis-794 cells. In addition, the difference of NO origin between plants and cyanobacteria are discussed.

Research notes : a little light reading.

DOT National Transportation Integrated Search

2001-01-01

The safety of nighttime drivers is enhanced by the better visibility of retroreflective pavement markings. Retroreflective markings reflect light (such as car headlights) back along the same path it came from -- in the case of headlights, back ...

Enhancements to pavement marking testing procedures.

DOT National Transportation Integrated Search

2010-08-01

The Oregon Department of Transportation (ODOT) requires performance and durability testing of all pavement : marking materials before they can be applied on construction projects on state highways. Manufacturers apply materials : on a two-year test d...

Background parenchymal enhancement in preoperative breast MRI.

PubMed

Kohara, Satoko; Ishigaki, Satoko; Satake, Hiroko; Kawamura, Akiko; Kawai, Hisashi; Kikumori, Toyone; Naganawa, Shinji

2015-08-01

We aimed to assess the influence of background parenchymal enhancement (BPE) on surgical planning performed using preoperative MRI for breast cancer evaluation. Between January 2009 and December 2010, 91 newly diagnosed breast cancer patients (mean age, 55.5 years; range, 30-88 years) who underwent preoperative bilateral breast MRI followed by planned breast conservation therapy were retrospectively enrolled. MRI was performed to assess the tumor extent in addition to mammography and breast ultrasonography. BPE in the contralateral normal breast MRI at the early dynamic phase was visually classified as follows: minimal (n=49), mild (n=27), moderate (n=7), and marked (n=8). The correlations between the BPE grade and age, menopausal status, index tumor size, changes in surgical management based on MRI results, positive predictive value (PPV) of MRI, and surgical margins were assessed. Patients in the strong BPE groups were significantly younger (p=0.002) and generally premenopausal (p<0.001). Surgical treatment was not changed in 67 cases (73.6%), while extended excision and mastectomy were performed in 12 cases (13.2%), each based on additional lesions on MRI. Six of 79 (7.6%) patients who underwent breast conservation therapy had tumor-positive resection margins. In cases where surgical management was changed, the PPV for MRI-detected foci was high in the minimal (91.7%) and mild groups (66.7%), and 0% in the moderate and marked groups (p=0.002). Strong BPE causes false-positive MRI findings and may lead to overly extensive surgery, whereas MRI may be beneficial in select patients with weak BPE.

Sparing of Sensitivity to Biological Motion but Not of Global Motion after Early Visual Deprivation

ERIC Educational Resources Information Center

Hadad, Bat-Sheva; Maurer, Daphne; Lewis, Terri L.

2012-01-01

Patients deprived of visual experience during infancy by dense bilateral congenital cataracts later show marked deficits in the perception of global motion (dorsal visual stream) and global form (ventral visual stream). We expected that they would also show marked deficits in sensitivity to biological motion, which is normally processed in the…

Involvement of up-regulated Necl-5/Tage4/PVR/CD155 in the loss of contact inhibition in transformed NIH3T3 cells

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

Minami, Yukiko; Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka; Ikeda, Wataru

2007-01-26

Normal cells show contact inhibition of cell movement and proliferation, but this is lost following transformation. We found that Necl-5, originally identified as a poliovirus receptor and up-regulated in many cancer cells, enhances growth factor-induced cell movement and proliferation. We showed that when cells contact other cells, Necl-5 interacts in trans with nectin-3 and is removed by endocytosis from the cell surface, resulting in a reduction of cell movement and proliferation. We show here that up-regulation of the gene encoding Necl-5 by the oncogene V12-Ki-Ras causes enhanced cell movement and proliferation. Upon cell-cell contact, de novo synthesis of Necl-5 exceedsmore » the rate of Necl-5 endocytosis, eventually resulting in a net increase in the amount of Necl-5 at the cell surface. In addition, expression of the gene encoding nectin-3 is markedly reduced in transformed cells. Thus, up-regulation of Necl-5 following transformation contributes to the loss of contact inhibition in transformed cells.« less

Preparation of laminin/nidogen adsorbed urinary bladder decellularized materials via a mussel-inspired polydopamine coating for pelvic reconstruction

PubMed Central

Ge, Liangpeng; Cao, Chuan; Chen, Shixuan; Shao, Bin; Li, Qianyong; Li, Qingtao; Liu, Lubin; Liang, Zhiqing; Huang, Yong

2017-01-01

Pelvic organ prolapse (POP) is a serious health issue that affects many adult women. A common strategy for POP reconstruction is to use scaffold materials to reconstruct the prolapsed pelvic organ. However, the existing materials for pelvic reconstruction do not meet the clinical requirements for biocompatibility, mechanics and immunological rejection. To address these concerns, urinary bladder decellularized materials (UBDM) was selected due to their good strain-stress resistance. To enhance its biocompatibility, laminin/nidogen was used to modify the UBDM with a mussel-inspired polydopamine coating. We found that the biocompatibility and mechanical properties of laminin/nidogen-Dopamine-UBDM were significantly enhanced and that the degradation rate of laminin/nidogen-Dopamine-UBDM was markedly reduced. Moreover, the expression of CD31 in the laminin/nidogen-Dopamine-UBDM group was higher than that in the normal UBDM group. The laminin/nidogen-Dopamine-UBDM treatment mainly guided M2 type macrophages and led to an inflammatory response. These results indicate that laminin/nidogen adsorbed urinary bladder decellularized materials are promising for use in pelvic reconstruction. PMID:29312483

Enteric oxalate elimination is induced and oxalate is normalized in a mouse model of primary hyperoxaluria following intestinal colonization with Oxalobacter

PubMed Central

Gjymishka, Altin; Salido, Eduardo C.; Allison, Milton J.; Freel, Robert W.

2011-01-01

Oxalobacter colonization of rat intestine was previously shown to promote enteric oxalate secretion and elimination, leading to significant reductions in urinary oxalate excretion (Hatch et al. Kidney Int 69: 691–698, 2006). The main goal of the present study, using a mouse model of primary hyperoxaluria type 1 (PH1), was to test the hypothesis that colonization of the mouse gut by Oxalobacter formigenes could enhance enteric oxalate secretion and effectively reduce the hyperoxaluria associated with this genetic disease. Wild-type (WT) mice and mice deficient in liver alanine-glyoxylate aminotransferase (Agxt) exhibiting hyperoxalemia and hyperoxaluria were used in these studies. We compared the unidirectional and net fluxes of oxalate across isolated, short-circuited large intestine of artificially colonized and noncolonized mice. In addition, plasma and urinary oxalate was determined. Our results demonstrate that the cecum and distal colon contribute significantly to enteric oxalate excretion in Oxalobacter-colonized Agxt and WT mice. In colonized Agxt mice, urinary oxalate excretion was reduced 50% (to within the normal range observed for WT mice). Moreover, plasma oxalate concentrations in Agxt mice were also normalized (reduced 50%). Colonization of WT mice was also associated with marked (up to 95%) reductions in urinary oxalate excretion. We conclude that segment-specific effects of Oxalobacter on intestinal oxalate transport in the PH1 mouse model are associated with a normalization of plasma oxalate and urinary oxalate excretion in otherwise hyperoxalemic and hyperoxaluric animals. PMID:21163900

HIV-antibody complexes enhance production of type I interferon by plasmacytoid dendritic cells

PubMed Central

Veenhuis, Rebecca T.; Freeman, Zachary T.; Korleski, Jack; Cohen, Laura K.; Tomasi, Alessandra; Boesch, Austin W.; Ackerman, Margaret E.; Margolick, Joseph B.; Blankson, Joel N.; Chattergoon, Michael A.; Cox, Andrea L.

2017-01-01

Type I IFN production is essential for innate control of acute viral infection; however, prolonged high-level IFN production is associated with chronic immune activation in HIV-infected individuals. Although plasmacytoid DCs (pDCs) are a primary source of IFN, the mechanisms that regulate IFN levels following the acute phase are unknown. We hypothesized that HIV-specific Ab responses regulate late IFN production. We evaluated the mechanism through which HIV-activated pDCs produce IFN as well as how both monoclonal HIV-specific Abs and Abs produced in natural HIV infection modulated normal pDC sensing of HIV. We found that HIV-induced IFN production required TLR7 signaling, receptor-mediated entry, fusion, and viral uncoating, but not endocytosis or HIV life cycle stages after uncoating. Abs directed against the HIV envelope that do not interfere with CD4 binding markedly enhanced the IFN response, irrespective of their ability to neutralize CD4+ T cell infection. Ab-mediated enhancement of IFN production required Fc γ receptor engagement, bypassed fusion, and initiated signaling through both TLR7 and TLR9, which was not utilized in the absence of Ab. Polyclonal Abs isolated from HIV-infected subjects also enhanced pDC production of IFN in response to HIV. Our data provide an explanation for high levels of IFN production and immune activation in chronic HIV infection. PMID:29083319

Mutations in ash1 and trx enhance P-element-dependent silencing in Drosophila melanogaster.

PubMed

McCracken, Allen; Locke, John

2016-08-01

In Drosophila melanogaster, the mini-w(+) transgene in Pci is normally expressed throughout the adult eye; however, when other P or KP elements are present, a variegated-eye phenotype results, indicating random w(+) silencing during development called P-element-dependent silencing (PDS). Mutant Su(var)205 and Su(var)3-7 alleles act as haplo-suppressors/triplo-enhancers of this variegated phenotype, indicating that these heterochromatic modifiers act dose dependently in PDS. Previously, we recovered a spontaneous mutation of P{lacW}ci(Dplac) called P{lacW}ci(DplacE1) (E1) that variegated in the absence of P elements, presumably due to the insertion of an adjacent gypsy element. From a screen for genetic modifiers of E1 variegation, we describe here the isolation of five mutations in ash1 and three in trx that enhance the E1 variegated phenotype in a dose-dependent and cumulative manner. These mutant alleles enhance PDS at E1, and in E1/P{lacW}ci(Dplac), but suppress position effect variegation (PEV) at In(1)w(m)(4). This opposite action is consistent with a model where ASH1 and TRX mark transcriptionally active chromatin domains. If ASH1 or TRX function is lost or reduced, heterochromatin can spread into these domains creating a sink that diverts heterochromatic proteins from other variegating locations, which then may express a suppressed phenotype.

Aldosterone synthase inhibition improves cardiovascular function and structure in rats with heart failure: a comparison with spironolactone.

PubMed

Mulder, Paul; Mellin, Virginie; Favre, Julie; Vercauteren, Magali; Remy-Jouet, Isabelle; Monteil, Christelle; Richard, Vincent; Renet, Sylvanie; Henry, Jean Paul; Jeng, Arco Y; Webb, Randy L; Thuillez, Christian

2008-09-01

Inhibition of aldosterone synthase, the key enzyme in aldosterone formation, could be an alternative strategy for mineralocorticoid-receptor antagonists in congestive heart failure (CHF), but its effect in CHF is unknown. We compared, in rats with CHF, the effects of a 7 day and a 12 week treatment with the aldosterone synthase inhibitor FAD286 (4 mg kg(-1) day(-1)) with those induced by spironolactone (80 mg kg(-1) day(-1)). FAD286/spironolactone increased cardiac output without modifying arterial pressure. Long-term FAD286 and spironolactone reduced left ventricular (LV) end-diastolic pressure, LV relaxation constant, and LV dilatation, and these effects were more marked with FAD286, whereas both drugs reduced LV hypertrophy and collagen accumulation to the same extent. Long-term FAD286/spironolactone prevented CHF-related enhancement in LV ACE and reduction in LV ACE-2, but only FAD286 prevented the reduction in LV AT(2) receptors. FAD286, but not long-term spironolactone, reduced the CHF-related enhancements in LV reactive oxygen species, reduced-oxidized glutathione ratio, and aortic nicotinamide adenine dinucleotide phosphate oxidase activity. FAD286 normalized the CHF-induced impairment of endothelium-dependent vasodilatation. In experimental CHF, FAD286 and spironolactone improve LV haemodynamics, remodelling, and function, but only FAD286 persistently normalizes LV 'redox status'. These results suggest that aldosterone synthase inhibition is a potential therapeutic strategy for the treatment of CHF.

Enhanced vasculotoxic metal excretion in post-myocardial infarction patients following a single edetate disodium-based infusion.

PubMed

Arenas, Ivan A; Navas-Acien, Ana; Ergui, Ian; Lamas, Gervasio A

2017-10-01

Toxic metals have been associated with cardiovascular mortality and morbidity. We have hypothesized that enhanced excretion of vasculotoxic metals might explain the positive results of the Trial to Assess Chelation Therapy (TACT). The purpose of this study was to determine whether a single infusion of the edetate disodium- based infusion used in TACT led to enhanced excretion of toxic metals known to be associated with cardiovascular events. Twenty six patients (post-MI, age > 50 years, serum creatinine ≤ 2.0mg/dL) were enrolled in this open-label study. Urinary levels of 20 toxic metals normalized to urinary creatinine concentrations were measured at baseline in overnight urine collections, for 6h following a placebo infusion of 500mL normal saline and 1.2% dextrose, and for 6h following a 3g edetate disodium-based infusion. Self-reported metal exposure, smoking status, food frequency, occupational history, drinking water source, housing and hobbies were collected at baseline by a metal exposure questionnaire. The mean age was 65 years (range 51-81 years). All patients were male. 50% had diabetes mellitus and 58% were former smokers. Mean (SD) serum creatinine was 0.95 (0.31) mg/dL. Toxic metals were detected in the baseline urine of >80% of patients. After placebo infusion there were no significant changes in total urinary metal levels. After edetate infusion, total urinary metal level increased by 71% compared to baseline (1500 vs. 2580µg/g creatinine; P<0.0001). The effect of edetate was particularly large for lead (3835% increase) and cadmium (633% increase). Edetate disodium-based infusions markedly enhanced the urinary excretion of lead and cadmium, toxic metals with established epidemiologic evidence and mechanisms linking them to coronary and vascular events. Copyright © 2017 Elsevier Inc. All rights reserved.

Airport pavement marking evaluation for reducing runway incursion

DOT National Transportation Integrated Search

2001-02-01

This study was undertaken to evaluate the widening of airport pavement marking in order to enhance their recognition. Results of this evaluation are aimed at reducing the potential of runway incursions and incidents by making airports pavement markin...

The radio-far infrared correlation: Spiral and blue compact dwarf galaxies opposed

NASA Technical Reports Server (NTRS)

Klein, U.; Wunderlich, E.

1987-01-01

The recently established correlation between radio continuum and far infrared emission in galaxies was further investigated by comparing normal spiral and blue compact dwarf galaxies. The puzzling result is that the ratio of radio to far infrared luminosity and its dispersion is the same for both samples, although their ratios of blue to far infrared luminosity, their radio spectral indices and their dust temperatures exhibit markedly different mean values and dispersions. This suggests that the amount of energy radiated in the two regimes is enhanced in the same way although the mechanisms responsible for the two components are rather different and complex. The fact that the blue light does not increase at the same proportion shows that both the radio and the far infrared emission are connected with the recent star formation history.

Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis.

PubMed

Hanada, Keigo; Furuya, Kazuyuki; Yamamoto, Noriko; Nejishima, Hiroaki; Ichikawa, Kiyonoshin; Nakamura, Tsutomu; Miyakawa, Motonori; Amano, Seiji; Sumita, Yuji; Oguro, Nao

2003-11-01

A novel nonsteroidal androgen receptor (AR) binder, S-40503, was successfully generated in order to develop selective androgen receptor modulators (SARMs). We evaluated the binding specificity for nuclear receptors (NRs) and osteoanabolic activities of S-40503 in comparison with a natural nonaromatizable steroid, 5alpha-dihydrotestosterone (DHT). The compound preferentially bound to AR with nanomolar affinity among NRs. When S-40503 was administrated into orchiectomized (ORX) rats for 4 weeks, bone mineral density (BMD) of femur and muscle weight of levator ani were increased as markedly as DHT, but prostate weight was not elevated over the normal at any doses tested. In contrast, DHT administration caused about 1.5-fold increase in prostate weight. The reduced virilizing activity was clearly evident from the result that 4-week treatment of normal rats with S-40503 showed no enlargement of prostate. To confirm the bone anabolic effect, S-40503 was given to ovariectomized (OVX) rats for 2 months. The compound significantly increased the BMD and biomechanical strength of femoral cortical bone, whereas estrogen, anti-bone resorptive hormone, did not. The increase in periosteal mineral apposition rate (MAR) of the femur revealed direct bone formation activity of S-40503. It was unlikely that the osteoanabolic effect of the compound was attribute to the enhancement of muscle mass, because immobilized ORX rats treated with S-40503 showed a marked increase in BMD of tibial cortical bone without any actions on the surrounding muscle tissue. Collectively, our novel compound served as a prototype for SARMs, which had unique tissue selectivity with high potency for bone formation and lower impact upon sex accessory tissues.

c-myc, c-fos, and c-jun regulation in the regenerating livers of normal and H-2K/c-myc transgenic mice.

PubMed Central

Morello, D; Fitzgerald, M J; Babinet, C; Fausto, N

1990-01-01

We investigated the mechanisms of regulation of c-myc, c-fos, and c-jun at the early stages of liver regeneration in mice. We show that the transient increase in steady-state levels of c-myc mRNA at the start of liver regeneration is most probably regulated by posttranscriptional mechanisms. Although there was a marked increase in c-myc transcriptional initiation shortly after partial hepatectomy, a block in elongation prevented the completion of most transcripts. To gain further information on the mechanism of regulation of c-myc expression during liver regeneration, we used transgenic mice harboring the human c-myc gene driven by the H-2K promoter. In these animals, the murine c-myc responded to the growth stimulus generated by partial hepatectomy, whereas the expression of the transgene was constitutive and did not change in the regenerating liver. However, the mRNA from both genes increased markedly after cycloheximide injection, suggesting that the regulation of c-myc mRNA abundance in the regenerating liver differs from that occurring after protein synthesis inhibition. Furthermore, we show that in normal mice c-fos and c-jun mRNA levels and transcriptional rates increase within 30 min after partial hepatectomy. c-fos transcriptional elongation was restricted in nongrowing liver, but the block was partially relieved in the regenerating liver. Nevertheless, for both c-fos and c-jun, changes in steady-state mRNA detected after partial hepatectomy were much greater than the transcriptional increase. In the regenerating liver of H-2K/c-myc mice, c-fos and c-jun expression was diminished, whereas mouse c-myc expression was enhanced in comparison with that in nontransgenic animals. Images PMID:2111449

The Stingless Bee Melipona solani Deposits a Signature Mixture and Methyl Oleate to Mark Valuable Food Sources.

PubMed

Alavez-Rosas, David; Malo, Edi A; Guzmán, Miguel A; Sánchez-Guillén, Daniel; Villanueva-Gutiérrez, Rogel; Cruz-López, Leopoldo

2017-10-01

Stingless bees foraging for food improve recruitment by depositing chemical cues on valuable food sites or pheromone marks on vegetation. Using gas chromatography/mass spectrometry and bioassays, we showed that Melipona solani foragers leave a mixture composed mostly of long chain hydrocarbons from their abdominal cuticle plus methyl oleate from the labial gland as a scent mark on rich food sites. The composition of hydrocarbons was highly variable among individuals and varied in proportions, depending on the body part. A wide ratio of compounds present in different body parts of the bees elicited electroantennogram responses from foragers and these responses were dose dependent. Generally, in bioassays, these bees prefer to visit previously visited feeders and feeders marked with extracts from any body part of conspecifics. The mean number of visits to a feeder was enhanced when synthetic methyl oleate was added. We propose that this could be a case of multi-source odor marking, in which hydrocarbons, found in large abundance, act as a signature mixture with attraction enhanced through deposition of methyl oleate, which may indicate a rich food source.

Clinical, cellular, microscopic, and ultrastructural studies of a case of fibrogenesis imperfecta ossium

PubMed Central

Barron, Melissa L; Rybchyn, Mark S; Ramesh, Sutharshani; Mason, Rebecca S; Fiona Bonar, S; Stalley, Paul; Khosla, Sundeep; Hudson, Bernie; Arthur, Christopher; Kim, Edward; Clifton-Bligh, Roderick J; Clifton-Bligh, Phillip B

2017-01-01

Fibrogenesis imperfecta ossium is a rare disorder of bone usually characterized by marked osteopenia and associated with variable osteoporosis and osteosclerosis, changing over time. Histological examination shows that newly formed collagen is abnormal, lacking birefringence when examined by polarized light. The case presented demonstrates these features and, in addition, a previously undocumented finding of a persistent marked reduction of the serum C3 and C4. Osteoblasts established in culture from a bone biopsy showed abnormal morphology on electron microscopy and increased proliferation when cultured with benzoylbenzoyl-ATP and 1,25-dihydroxyvitamin D, contrasting with findings in normal osteoblasts in culture. A gene microarray study showed marked upregulation of the messenger RNA (mRNA) for G-protein-coupled receptor 128 (GPR 128), an orphan receptor of unknown function and also of osteoprotegerin in the patient’s osteoblasts in culture. When normal osteoblasts were cultured with the patient’s serum, there was marked upregulation of the mRNA for aquaporin 1. A single pathogenetic factor to account for the features of this disorder has not been defined, but the unique findings described here may facilitate more definitive investigation of the abnormal bone cell function. PMID:28326223

Strategies for enhancing catecholamine-mediated neurotransmission

NASA Technical Reports Server (NTRS)

Wurtman, Richard J.

1992-01-01

Major findings made during this project period included the following observations: changes in tyrosine availability do affect brain dopamine release, as assessed by in vivo microdialysis, but that neuronal feedback mechanisms limit the durations of this effect except when dopaminergic neurotransmission has been deficient; the circulating hormone TRH markedly stimulates brain dopamine release, an effect probably mediated by its diketopiperazine metabolite; the amount of circulating L-dopa which enters the brain is both enhanced by carbohydrate consumption and suppressed by protein intake (both nutritional effects can be damaging, inasmuch as a sudden rush of L-dopa into the brain can facilitate dyskinesias, while the inhibition of brain L-dopa uptake by proteins suppresses its conversion to brain dopamine; an appropriate mixture of dietary proteins and carbohydrates can obviate both effects); serotonin release from superfused hypothalamic slices is a linear function of available tryptophan levels throughout the normal dynamic range; the daily rhythm in plasma melatonin levels is abnormal both in the sudden infant death syndrome and in women with secondary amenorrhea; tyrosine can potentiate the anorectic effects of widely-used sympathomimetic drugs; newly-described COMT inhibitors can enhance brain dopamine release in vivo; and a cell culture system, based on Y-79 (retinoblast) cells, exists in which melatonin reliably suppresses dopamine release.

Enhancement of solubility and antidiabetic effects of Repaglinide using spray drying technique in STZ-induced diabetic rats.

PubMed

Varshosaz, Jaleh; Minayian, Mohsen; Ahmadi, Mahdieh; Ghassami, Erfaneh

2017-09-01

The purpose of the study was to enhance the solubility of the poorly water-soluble drug, Repaglinide using spray drying based solid dispersion technique by different carriers including Eudragit E100, hydroxyl propyl cellulose Mw 80 000 and poly vinyl pyrollidone K30. Optimization of the best formulation was carried out according to drug solubility, release profile, particle size and angle of repose of the solid dispersions. The optimized sample was characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The morphology of the dispersions was studied by SEM. The blood glucose lowering effect of spray dried solid dispersions was studied in normal and streptozocin-induced diabetic rats. The results showed that Eudragit E100 in 1:3 ratio could enhance drug solubility by 100-fold. DSC studies indicated a marked change in melting point of the drug possibly due to strong hydrogen bonds between the drug and Eudragit, while FT-IR study did not show obvious interactions between them. According to XRPD results Repaglinide converted to an amorphous state in the spray dried dispersions. Spray dried Repaglinide reduced the blood glucose level significantly during the 8 h of obtaining blood samples in comparison with untreated drug (p < 0.05).

Peptidyl-prolyl Cis/Trans Isomerase NIMA-interacting 1 Associates with Insulin Receptor Substrate-1 and Enhances Insulin Actions and Adipogenesis

PubMed Central

Nakatsu, Yusuke; Sakoda, Hideyuki; Kushiyama, Akifumi; Zhang, Jun; Ono, Hiraku; Fujishiro, Midori; Kikuchi, Takako; Fukushima, Toshiaki; Yoneda, Masayasu; Ohno, Haruya; Horike, Nanao; Kanna, Machi; Tsuchiya, Yoshihiro; Kamata, Hideaki; Nishimura, Fusanori; Isobe, Toshiaki; Ogihara, Takehide; Katagiri, Hideki; Oka, Yoshitomo; Takahashi, Shin-ichiro; Kurihara, Hiroki; Uchida, Takafumi; Asano, Tomoichiro

2011-01-01

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is a unique enzyme that associates with the pSer/Thr-Pro motif and catalyzes cis-trans isomerization. We identified Pin1 in the immunoprecipitates of overexpressed IRS-1 with myc and FLAG tags in mouse livers and confirmed the association between IRS-1 and Pin1 by not only overexpression experiments but also endogenously in the mouse liver. The analysis using deletion- and point-mutated Pin1 and IRS-1 constructs revealed the WW domain located in the N terminus of Pin1 and Ser-434 in the SAIN (Shc and IRS-1 NPXY binding) domain of IRS-1 to be involved in their association. Subsequently, we investigated the role of Pin1 in IRS-1 mediation of insulin signaling. The overexpression of Pin1 in HepG2 cells markedly enhanced insulin-induced IRS-1 phosphorylation and its downstream events: phosphatidylinositol 3-kinase binding with IRS-1 and Akt phosphorylation. In contrast, the treatment of HepG2 cells with Pin1 siRNA or the Pin1 inhibitor Juglone suppressed these events. In good agreement with these in vitro data, Pin1 knock-out mice exhibited impaired insulin signaling with glucose intolerance, whereas adenoviral gene transfer of Pin1 into the ob/ob mouse liver mostly normalized insulin signaling and restored glucose tolerance. In addition, it was also demonstrated that Pin1 plays a critical role in adipose differentiation, making Pin1 knock-out mice resistant to diet-induced obesity. Importantly, Pin1 expression was shown to be up-regulated in accordance with nutrient conditions such as food intake or a high-fat diet. Taken together, these observations indicate that Pin1 binds to IRS-1 and thereby markedly enhances insulin action, essential for adipogenesis. PMID:21454638

Estimating and testing interactions when explanatory variables are subject to non-classical measurement error.

PubMed

Murad, Havi; Kipnis, Victor; Freedman, Laurence S

2016-10-01

Assessing interactions in linear regression models when covariates have measurement error (ME) is complex.We previously described regression calibration (RC) methods that yield consistent estimators and standard errors for interaction coefficients of normally distributed covariates having classical ME. Here we extend normal based RC (NBRC) and linear RC (LRC) methods to a non-classical ME model, and describe more efficient versions that combine estimates from the main study and internal sub-study. We apply these methods to data from the Observing Protein and Energy Nutrition (OPEN) study. Using simulations we show that (i) for normally distributed covariates efficient NBRC and LRC were nearly unbiased and performed well with sub-study size ≥200; (ii) efficient NBRC had lower MSE than efficient LRC; (iii) the naïve test for a single interaction had type I error probability close to the nominal significance level, whereas efficient NBRC and LRC were slightly anti-conservative but more powerful; (iv) for markedly non-normal covariates, efficient LRC yielded less biased estimators with smaller variance than efficient NBRC. Our simulations suggest that it is preferable to use: (i) efficient NBRC for estimating and testing interaction effects of normally distributed covariates and (ii) efficient LRC for estimating and testing interactions for markedly non-normal covariates. © The Author(s) 2013.

Transperineal ultrasound in the assessment of haemorrhoids and haemorrhoidectomy: a pilot study.

PubMed

Zbar, A P; Murison, R

2010-06-01

The purpose of the study was the measurement of the anal cushion area using static transperineal ultrasound in a group of patients with symptomatic grade III and IV haemorrhoids about to undergo haemorrhoidectomy and compare them with a group of age-matched normals and the measured area following haemorrhoidectomy. Transperineal sonography was performed using a linear transducer measuring the anal cushion area by subtracting the measured luminal diameter of the undisturbed anal canal from the inner border of the internal anal sphincter. Measures were made 6 weeks following haemorrhoidectomy. Comparisons were made between 22 normals and 36 patients with haemorrhoids (31 evaluable post-operatively). The median area of normals was 0.78 cm², that of pre-operative patients 2.25 cm² and that of post-operative cases 1.20 cm². There was a significant difference between pre- and post-operative cases with cushion areas of normal patients being significantly lower than post-operative cases. Variance of measurement in all 3 groups was negligible. Static transperineal sonography measuring the anal cushion area is reproducible and shows marked differences between normals and patients with symptomatic haemorrhoids. There is a marked effect on measured area resultant from haemorrhoidectomy.

Prenatal development of the normal human vertebral corpora in different segments of the spine.

PubMed

Nolting, D; Hansen, B F; Keeling, J; Kjaer, I

1998-11-01

Vertebral columns from 13 normal human fetuses (10-24 weeks of gestation) that had aborted spontaneously were investigated as part of the legal autopsy procedure. The investigation included spinal cord analysis. To analyze the formation of the normal human vertebral corpora along the spine, including the early location and disappearance of the notochord. Reference material on the development of the normal human vertebral corpora is needed for interpretation of published observations on prenatal malformations in the spine, which include observations of various types of malformation (anencephaly, spina bifida) and various genotypes (trisomy 18, 21 and 13, as well as triploidy). The vertebral columns were studied by using radiography (Faxitron X-ray apparatus, Faxitron Model 43,855, Hewlett Packard) in lateral, frontal, and axial views and histology (decalcification, followed by toluidine blue and alcian blue staining) in and axial view. Immunohistochemical marking with Keratin Wide Spectrum also was done. Notochordal tissue (positive on marking with Keratin Wide Spectrum [DAKO, Denmark]) was located anterior to the cartilaginous body center in the youngest fetuses. The process of disintegration of the notochord and the morphology of the osseous vertebral corpora in the lumbosacral, thoracic, and cervical segments are described. Marked differences appeared in axial views, which were verified on horizontal histologic sections. Also, the increase in size was different in the different segments, being most pronounced in the thoracic and upper lumbar bodies. The lower thoracic bodies were the first to ossify. The morphologic changes observed by radiography were verified histologically. In this study, normal prenatal standards were established for the early development of the vertebral column. These standards can be used in the future--for evaluation of pathologic deviations in the human vertebral column in the second trimester.

Prayer Marks in Immigrants from Bangladesh with Diabetes Who Live in Greece.

PubMed

Papadakis, G; Zampelis, T; Michalopoulou, M; Konstantopoulos, K; Rosenberg, T; Chatzipanagiotou, S

2016-02-01

Prayer marks (PMs) are commonly occurring dermatologic changes in muslims who pray and develop over a long period of time as a consequence of repeated and extended pressure. PMs need careful examination especially for patients with diabetes, who are more vulnerable due to predisposing factors such as venous insufficiency and peripheral neuropathy. A total of 166 patients with diabetes (150 males, 16 females) and 65 normal subjects from Bangladesh were examined for the appearance of PMs. Twenty-eight patients (16.9 %) and one normal subject (1.5 %) had PMs. The marks were not itchy or painful and they were observed on the dorsal aspect of the left foot, which was attributed to a more typical prayer position that placed pressure on the left foot. PMs are not a rare clinical entity among muslim patients with diabetes and most clinicians should be aware of it as it can be the predominant cause of an ulcer.

A case of severe sepsis presenting marked decrease of neutrophils and interesting findings on dynamic CT.

PubMed

Makino, Isamu; Tajima, Hidehiro; Kitagawa, Hirohisa; Nakagawara, Hisatoshi; Miyashita, Tomoharu; Nakanuma, Shinichi; Hayashi, Hironori; Takamura, Hiroyuki; Fushida, Sachio; Ohta, Tetsuo

2015-05-28

In a patient with severe sepsis, we sometimes observe immediate decrease of the counts of white blood cells (WBCs) and neutrophils, which is known as an indicator for poor prognosis. We observed marked decrease of white blood cells and neutrophils on blood examination and interesting findings on dynamic CT. Here, we present the case of a patient with severe postoperative sepsis occurring after major abdominal surgery and we discuss the mechanism of such clinical presentations. A 60-year-old man received pancreatoduodenectomy with colectomy for pancreatic cancer. He developed a high fever on postoperative day 3. We observed marked decrease of WBCs and neutrophils on blood examination. We also observed slight swelling of the liver, inhomogeneous enhancement of liver parenchyma in arterial phase, and periportal low density in the Glisson capsule in portal phase, without any findings indicating infectious complications on dynamic CT. WBCs and neutrophils increased above normal range in just 6 hours. Blood culture examination performed while the patient had a high fever was positive for Aeromonas hydrophila. After receiving intensive care, he promptly recovered from severe sepsis. The CT findings disappeared on second dynamic CT examination performed 3 days after the first examination. We treated a patient with severe sepsis after major abdominal surgery who presented very rapid change of the counts of WBCs and neutrophils and interesting CT findings in the liver. We rescued him from a critical situation by prompt and intensive treatment. Research is needed to accumulate and analyze data from more patients who present a similar clinical course to better understand their pathophysiological conditions.

Eosinophilic myocarditis due to Churg-Strauss syndrome with markedly elevated eosinophil cationic protein.

PubMed

Hara, Tomoya; Yamaguchi, Koji; Iwase, Takashi; Kadota, Muneyuki; Bando, Mika; Ogasawara, Kozue; Bando, Sachiko; Ise, Takayuki; Niki, Toshiyuki; Ueda, Yuka; Tomita, Noriko; Taketani, Yoshio; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Sata, Masataka

2013-01-01

A 67-year-old woman with asthma visited our hospital with increasing dyspnea and new-onset paresthesia and purpura in her legs. Physical examination showed a wheeze, pretibial edema, and surrounding purpura. Chest X-rays showed cardiac decompensation and an electrocardiogram revealed a new ST-T change. Laboratory data showed leukocytosis, hypereosinophilia (10,450/μL), troponin T(+), elevated BNP, and markedly elevated eosinophil cationic protein (ECP) (> 150 ng/mL). Echocardiography revealed diffuse left ventricular hypokinesis (ejection fraction 30%) with increased wall thickness. Coronary angiography was normal. Cardiac magnetic resonance imaging implied diffuse myocardial edema and subendocardial late gadolinium enhancement. Skin biopsy of purpura showed superfi cial perivascular dermatitis with remarkable eosinophilic infiltrations. No evidence of drug allergies, parasitic infection, or myeloproliferative disorder was detected. Based on these findings, a diagnosis of eosinophilic myocarditis due to Churg-Strauss syndrome was considered. She was administered prednisolone at a dose of 1 mg/kg, cyclophosphamide, and diuretics. Several markers of eosinophilic myocarditis and heart failure gradually improved, including ECP. She was discharged 30 days later with no cardiac event. Eosinophilic myocarditis is characterized by predominantly eosinophilic infi ltration. Eosinophilic granule proteins, such as ECP and major basic protein, play important roles in the pathogenesis of eosinophilic myocarditis. We experienced a rare case of eosinophilic myocarditis due to Churg-Strauss syndrome. Markedly elevated ECP played an important role in the early diagnosis and subsequent reduction in ECP served as a marker of monitoring. In an asthmatic patient with dyspnea, hypereosinophilia, and vasculitis, Churg-Strauss syndrome with eosinophilic myocarditis should be considered.

Mosaic compound heterozygosity of SHOX resulting in Leri-Weill dyschondrosteosis with marked short stature: implications for disease mechanisms and recurrence risks.

PubMed

Reish, Orit; Huber, Céline; Altarescu, Gheona; Chapman-Shimshoni, Daphne; Levy-Lahad, Ephrat; Renbaum, Paul; Mashevich, Maya; Munnich, Arnold; Cormier-Daire, Valérie

2010-09-01

Mutations or deletions in the SHOX gene cause Leri-Weill dyschondrosteosis (LWD) and Langer mesomelic dysplasia (LMD) when present in heterozygous or homozygous form, respectively. A new class of enhancer deletions was identified 30-250 kb downstream of SHOX. We identified a female patient with marked short stature, mosaic for monosomy X in 31% of her lymphocytes, and findings consistent with LWD. Additional molecular studies demonstrated segregation of 17 polymorphic markers flanking and including the SHOX locus, spanning 328 kb of pseudoautosomal region 1 (PAR1) region. A deletion up to 10 kb residing 197 kb downstream of SHOX gene was detected, which was germinally transmitted from her clinically unaffected father. This was associated with post-zygotic mosaic loss of the normal maternal X-chromosome, evidenced by fluorescent fragment analysis. Since most patients with LMD with deletions downstream of SHOX gene also have SHOX mutations in trans, it may suggest these deletions are associated with a milder phenotype. Further studies are required to elucidate the role of the former region in disease etiology. Mutations should be sought in clinically non-affected family members because of the variable expressivity in hemizygous carriers, and cytogenetic evaluation should be considered to detect possible X-chromosome rearrangements underlying the haploinsufficiency for the PAR1 when deletion is detected by molecular analysis. Similarly, when LWD and marked short stature occur in a patient with mosaic Turner syndrome, the possibility of mutations in SHOX and the downstream of SHOX gene should be considered. Copyright 2010 Wiley-Liss, Inc.

Peripheral cannabinoid receptor, CB2, regulates bone mass

PubMed Central

Ofek, Orr; Karsak, Meliha; Leclerc, Nathalie; Fogel, Meirav; Frenkel, Baruch; Wright, Karen; Tam, Joseph; Attar-Namdar, Malka; Kram, Vardit; Shohami, Esther; Mechoulam, Raphael; Zimmer, Andreas; Bab, Itai

2006-01-01

The endogenous cannabinoids bind to and activate two G protein-coupled receptors, the predominantly central cannabinoid receptor type 1 (CB1) and peripheral cannabinoid receptor type 2 (CB2). Whereas CB1 mediates the cannabinoid psychotropic, analgesic, and orectic effects, CB2 has been implicated recently in the regulation of liver fibrosis and atherosclerosis. Here we show that CB2-deficient mice have a markedly accelerated age-related trabecular bone loss and cortical expansion, although cortical thickness remains unaltered. These changes are reminiscent of human osteoporosis and may result from differential regulation of trabecular and cortical bone remodeling. The CB2–/– phenotype is also characterized by increased activity of trabecular osteoblasts (bone-forming cells), increased osteoclast (the bone-resorbing cell) number, and a markedly decreased number of diaphyseal osteoblast precursors. CB2 is expressed in osteoblasts, osteocytes, and osteoclasts. A CB2-specific agonist that does not have any psychotropic effects enhances endocortical osteoblast number and activity and restrains trabecular osteoclastogenesis, apparently by inhibiting proliferation of osteoclast precursors and receptor activator of NF-κB ligand expression in bone marrow-derived osteoblasts/stromal cells. The same agonist attenuates ovariectomy-induced bone loss and markedly stimulates cortical thickness through the respective suppression of osteoclast number and stimulation of endocortical bone formation. These results demonstrate that the endocannabinoid system is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling. Hence, CB2 offers a molecular target for the diagnosis and treatment of osteoporosis, the most prevalent degenerative disease in developed countries. PMID:16407142

An ordinary differential equation model for full thickness wounds and the effects of diabetes.

PubMed

Bowden, L G; Maini, P K; Moulton, D E; Tang, J B; Wang, X T; Liu, P Y; Byrne, H M

2014-11-21

Wound healing is a complex process in which a sequence of interrelated phases contributes to a reduction in wound size. For diabetic patients, many of these processes are compromised, so that wound healing slows down. In this paper we present a simple ordinary differential equation model for wound healing in which attention focusses on the dominant processes that contribute to closure of a full thickness wound. Asymptotic analysis of the resulting model reveals that normal healing occurs in stages: the initial and rapid elastic recoil of the wound is followed by a longer proliferative phase during which growth in the dermis dominates healing. At longer times, fibroblasts exert contractile forces on the dermal tissue, the resulting tension stimulating further dermal tissue growth and enhancing wound closure. By fitting the model to experimental data we find that the major difference between normal and diabetic healing is a marked reduction in the rate of dermal tissue growth for diabetic patients. The model is used to estimate the breakdown of dermal healing into two processes: tissue growth and contraction, the proportions of which provide information about the quality of the healed wound. We show further that increasing dermal tissue growth in the diabetic wound produces closure times similar to those associated with normal healing and we discuss the clinical implications of this hypothesised treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of Corynebacterium parvum on the humoral and cellular immune systems in patients with breast cancer.

PubMed Central

Minton, J P; Rossio, J L; Dixon, B; Dodd, M C

1976-01-01

Corynebacterium parvum, a Gram-positive anaerobic bacillus thought to be a strong immunological stimulant, has been shown to decrease tumour growth and prolong survival in patients with metastatic disease. Study of the effect of a single injection of a strain of C. parvum (CN. 6134) in six patients with stage IV metastatic breast cancer is reported. Results of laboratory tests to judge the physical and immunological effects of the drug infusion 24 hr post-treatment and weekly thereafter for 3 weeks are evaluated. Within 24 hr after C. parvum administration, most patients experienced fever and nausea. Blood counts and differential counts exhibited increased values 24 hr after treatment with a strong shift to the left. Lymphocyte and monocyte counts were greatly depressed at 24 hr. T-cell numbers in peripheral blood did not appear to be altered, but the picture with regard to B cells was less clear. Normal count was recovered by day 8. It appears that intravenous administration of C. parvum produces a temporary marked immunological depression which returns to essentially normal values in 8 days. The return to normal may be accompanied by resolution of the endotoxin-like syndrome of side-effects. Further study of patients receiving this therapeutic agent is important to detect enhancement of the anti-tumour immunological response precipitated. PMID:1084821

Management of Severe Rhabdomyolysis and Exercise-Associated Hyponatremia in a Female with Anorexia Nervosa and Excessive Compulsive Exercising

PubMed Central

2016-01-01

This case report describes the management of a 49-year-old female with restricting-type anorexia nervosa and excessive compulsive exercising associated with rhabdomyolysis, high levels of serum creatine kinase (CK) (3,238 U/L), and marked hyponatremia (Na+: 123 mEq/L) in the absence of purging behaviours or psychogenic polydipsia; it is the first case report to describe exercise-associated hyponatremia in a patient with anorexia nervosa. The patient, who presented with a body mass index (BMI) of 13.4 kg/m2, was successfully treated by means of an adapted inpatient version of an enhanced form of cognitive behavioural therapy (CBT-E). Within a few days, careful water restriction, solute refeeding, and the specific cognitive behavioural strategies and procedures used to address the patient's excessive compulsive exercising and undereating produced a marked reduction in CK levels, which normalised within one week. Exercise-associated hyponatremia also gradually improved, with serum sodium levels returning to normal within two weeks. The patient thereby avoided severe complications such as cerebral or pulmonary oedema or acute renal failure and was discharged after 20 weeks of treatment with a BMI of 19.0 kg/m2 and improved eating disorder psychopathology. PMID:27721832

Management of Severe Rhabdomyolysis and Exercise-Associated Hyponatremia in a Female with Anorexia Nervosa and Excessive Compulsive Exercising.

PubMed

El Ghoch, Marwan; Calugi, Simona; Dalle Grave, Riccardo

2016-01-01

This case report describes the management of a 49-year-old female with restricting-type anorexia nervosa and excessive compulsive exercising associated with rhabdomyolysis, high levels of serum creatine kinase (CK) (3,238 U/L), and marked hyponatremia (Na + : 123 mEq/L) in the absence of purging behaviours or psychogenic polydipsia; it is the first case report to describe exercise-associated hyponatremia in a patient with anorexia nervosa. The patient, who presented with a body mass index (BMI) of 13.4 kg/m 2 , was successfully treated by means of an adapted inpatient version of an enhanced form of cognitive behavioural therapy (CBT-E). Within a few days, careful water restriction, solute refeeding, and the specific cognitive behavioural strategies and procedures used to address the patient's excessive compulsive exercising and undereating produced a marked reduction in CK levels, which normalised within one week. Exercise-associated hyponatremia also gradually improved, with serum sodium levels returning to normal within two weeks. The patient thereby avoided severe complications such as cerebral or pulmonary oedema or acute renal failure and was discharged after 20 weeks of treatment with a BMI of 19.0 kg/m 2 and improved eating disorder psychopathology.

Tinnitus Perception and Distress Is Related to Abnormal Spontaneous Brain Activity as Measured by Magnetoencephalography

PubMed Central

Weisz, Nathan; Moratti, Stephan; Meinzer, Marcus; Dohrmann, Katalin; Elbert, Thomas

2005-01-01

Background The neurophysiological mechanisms underlying tinnitus perception are not well understood. Surprisingly, there have been no group studies comparing abnormalities in ongoing, spontaneous neuronal activity in individuals with and without tinnitus perception. Methods and Findings Here, we show that the spontaneous neuronal activity of a group of individuals with tinnitus (n = 17) is characterised by a marked reduction in alpha (8–12 Hz) power together with an enhancement in delta (1.5–4 Hz) as compared to a normal hearing control group (n = 16). This pattern was especially pronounced for temporal regions. Moreover, correlations with tinnitus-related distress revealed strong associations with this abnormal spontaneous activity pattern, particularly in right temporal and left frontal areas. Overall, effects were stronger for the alpha than for the delta frequency band. A data stream of 5 min, recorded with a whole-head neuromagnetometer under a resting condition, was sufficient to extract the marked differences. Conclusions Despite some limitations, there are arguments that the regional pattern of abnormal spontaneous activity we found could reflect a tinnitus-related cortical network. This finding, which suggests that a neurofeedback approach could reduce the adverse effects of this disturbing condition, could have important implications for the treatment of tinnitus. PMID:15971936

[Intracranial granulocytic sarcoma extending from the posterior fossa to the carotid space via the jugular foramen: a case report].

PubMed

Baba, Shiro; Matsuo, Takayuki; Ishizaka, Shunsuke; Morikawa, Minoru; Suyama, Kazuhiko; Nagata, Izumi

2010-01-01

Granulocytic sarcoma consists of neoplastic granulocytic precursors and myeloblasts. It is a focal lesion seen in 2-10.9% of acute myelogenous leukaemia (AML) patients. It usually develops either concurrently with the AML or after a remission. On rare occasions, it may be an initial manifestation of AML. Most common involvement sites are bone, periostium, soft tissue, lymph nodes and skin. Intracranial granulocytic sarcoma rarely occurs in meningeal or parenchymal form. We present an extremely rare case of intracranial granulocytic sarcoma extending from the posterior fossa to the carotid space via the jugular foramen in a 69 year old female. This form of involvement has not been previously reported. On MRI, the lesion appears isointense compared with normal grey matter in T1 and T2 weighted images and shows homogeneous contrast enhancement. With these findings, it is difficult to differentiate the lesion from other extraaxial tumours such as meningioma, paraganglioma, schwannoma, carcinoma, metastatic tumor, malignant lymphoma. However, granulocytic sarcoma, densely increased tumour cells restrict diffusion and reduce the extracellular volume fraction, tends to be markedly hyperintense on diffusion-weighted MR images and exhibits a marked decrease in ADC values. Therefore, DWI may be helpful in differentiating granulocytic sarcoma from other intracranial lesions.

Variations in Articulatory Movement with Changes in Speech Task.

ERIC Educational Resources Information Center

Tasko, Stephen M.; McClean, Michael D.

2004-01-01

Studies of normal and disordered articulatory movement often rely on the use of short, simple speech tasks. However, the severity of speech disorders can be observed to vary markedly with task. Understanding task-related variations in articulatory kinematic behavior may allow for an improved understanding of normal and disordered speech motor…

Beyond δ : Tailoring marked statistics to reveal modified gravity

NASA Astrophysics Data System (ADS)

Valogiannis, Georgios; Bean, Rachel

2018-01-01

Models that seek to explain cosmic acceleration through modifications to general relativity (GR) evade stringent Solar System constraints through a restoring, screening mechanism. Down-weighting the high-density, screened regions in favor of the low density, unscreened ones offers the potential to enhance the amount of information carried in such modified gravity models. In this work, we assess the performance of a new "marked" transformation and perform a systematic comparison with the clipping and logarithmic transformations, in the context of Λ CDM and the symmetron and f (R ) modified gravity models. Performance is measured in terms of the fractional boost in the Fisher information and the signal-to-noise ratio (SNR) for these models relative to the statistics derived from the standard density distribution. We find that all three statistics provide improved Fisher boosts over the basic density statistics. The model parameters for the marked and clipped transformation that best enhance signals and the Fisher boosts are determined. We also show that the mark is useful both as a Fourier and real-space transformation; a marked correlation function also enhances the SNR relative to the standard correlation function, and can on mildly nonlinear scales show a significant difference between the Λ CDM and the modified gravity models. Our results demonstrate how a series of simple analytical transformations could dramatically increase the predicted information extracted on deviations from GR, from large-scale surveys, and give the prospect for a much more feasible potential detection.

VEGF-Trap: a VEGF blocker with potent antitumor effects.

PubMed

Holash, Jocelyn; Davis, Sam; Papadopoulos, Nick; Croll, Susan D; Ho, Lillian; Russell, Michelle; Boland, Patricia; Leidich, Ray; Hylton, Donna; Burova, Elena; Ioffe, Ella; Huang, Tammy; Radziejewski, Czeslaw; Bailey, Kevin; Fandl, James P; Daly, Tom; Wiegand, Stanley J; Yancopoulos, George D; Rudge, John S

2002-08-20

Vascular endothelial growth factor (VEGF) plays a critical role during normal embryonic angiogenesis and also in the pathological angiogenesis that occurs in a number of diseases, including cancer. Initial attempts to block VEGF by using a humanized monoclonal antibody are beginning to show promise in human cancer patients, underscoring the importance of optimizing VEGF blockade. Previous studies have found that one of the most effective ways to block the VEGF-signaling pathway is to prevent VEGF from binding to its normal receptors by administering decoy-soluble receptors. The highest-affinity VEGF blocker described to date is a soluble decoy receptor created by fusing the first three Ig domains of VEGF receptor 1 to an Ig constant region; however, this fusion protein has very poor in vivo pharmacokinetic properties. By determining the requirements to maintain high affinity while extending in vivo half life, we were able to engineer a very potent high-affinity VEGF blocker that has markedly enhanced pharmacokinetic properties. This VEGF-Trap effectively suppresses tumor growth and vascularization in vivo, resulting in stunted and almost completely avascular tumors. VEGF-Trap-mediated blockade may be superior to that achieved by other agents, such as monoclonal antibodies targeted against the VEGF receptor.

Iodophenylpentadecanoic acid-myocardial blood flow relationship during maximal exercise with coronary occlusion.

PubMed

Caldwell, J H; Martin, G V; Link, J M; Krohn, K A; Bassingthwaighte, J B

1990-01-01

Imaging 123I-labeled iodophenylpentadecanoic acid (IPPA) uptake and clearance from the myocardium following exercise has been advocated as a means of detecting myocardial ischemia because fatty acid deposition is enhanced and clearance prolonged in regions of low flow. However, normal regional myocardial blood flows are markedly heterogeneous, and it is not known how this heterogeneity affects regional metabolism or substrate uptake and thus image interpretation. In five instrumented dogs running at near maximal workload on a treadmill, 131I-labeled IPPA and 15-micron 46Sc microspheres were injected into the left atrium after 30 sec of circumflex coronary artery occlusion. Microsphere and IPPA activity were determined in 250 mapped pieces of myocardium of approximately 400 mg. Myocardial blood flows (from microspheres) ranged from 0.05 to 7.6 ml/min/g. Deposition of IPPA was proportional to regional flows (r = 0.83) with an average retention of 25%. The mean endocardial-epicardial ratio for IPPA (0.90 +/- 0.43) was similar to that for microspheres (0.94 +/- 0.47; p = 0.08). Thus, initial IPPA deposition during treadmill exercise increases in proportion to regional myocardial blood flow over a range of flows from very low to five times normal.

Investigation of cytokines, oxidative stress, metabolic, and inflammatory biomarkers after orange juice consumption by normal and overweight subjects

PubMed Central

Dourado, Grace K. Z. S.; Cesar, Thais B.

2015-01-01

Background Abdominal adiposity has been linked to metabolic abnormalities, including dyslipidemia, oxidative stress, and low-grade inflammation. Objective To test the hypothesis that consumption of 100% orange juice (OJ) would improve metabolic, oxidative, and inflammatory biomarkers and cytokine levels in normal and overweight subjects with increased waist circumference. Design Subjects were divided into two groups in accordance with their body mass index: normal and overweight. Both groups of individuals consumed 750 mL of OJ daily for 8 weeks. Body composition (weight, height, percentage of fat mass, and waist circumference); metabolic biomarkers (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], triglycerides, glucose, insulin, HOMA-IR, and glycated hemoglobin); oxidative biomarkers (malondialdehyde and DPPH•); inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP]); cytokines (IL-4, IL-10, IL-12, TNF-α, and IFN-γ); and diet were evaluated before and after consumption of OJ for 8 weeks. Results The major findings of this study were: 1) no alteration in body composition in either group; 2) improvement of the lipid profile, evidenced by a reduction in total cholesterol and LDL-C; 3) a potential stimulation of the immune response due to increase in IL-12; 4) anti-inflammatory effect as a result of a marked reduction in hsCRP; and 5) antioxidant action by the enhancement of total antioxidant capacity and the reduction of lipid peroxidation, in both normal and overweight subjects. Conclusions OJ consumption has a positive effect on important biomarkers of health status in normal and overweight subjects, thereby supporting evidence that OJ acts as functional food and could be consumed as part of a healthy diet to prevent metabolic and chronic diseases. PMID:26490535

Lane marking detection based on waveform analysis and CNN

NASA Astrophysics Data System (ADS)

Ye, Yang Yang; Chen, Hou Jin; Hao, Xiao Li

2017-06-01

Lane markings detection is a very important part of the ADAS to avoid traffic accidents. In order to obtain accurate lane markings, in this work, a novel and efficient algorithm is proposed, which analyses the waveform generated from the road image after inverse perspective mapping (IPM). The algorithm includes two main stages: the first stage uses an image preprocessing including a CNN to reduce the background and enhance the lane markings. The second stage obtains the waveform of the road image and analyzes the waveform to get lanes. The contribution of this work is that we introduce local and global features of the waveform to detect the lane markings. The results indicate the proposed method is robust in detecting and fitting the lane markings.

Drugs of abuse and virus susceptibility.

PubMed

Friedman, H; Klein, T; Specter, S; Pross, S; Newton, C; Blanchard, D K; Widen, R

1988-01-01

It is widely recognized that various microorganisms including viruses have immunomodulatory effects and, under appropriate circumstances, may markedly suppress the immune response mechanisms. Cannabinoids present in marijuana also have immunomodulatory effects. In the present studies THC as well as its metabolic product 11-OH THC were studied in regard to their effects in vivo and in vitro on selected parameters of the immune response system known to be important in antiviral resistance, including immunity to retroviruses. Cannabinoids markedly suppressed the ability of murine macrophages to spread on glass (an important functional marker of macrophages) as well as to phagocytize yeast particles. Splenic macrophage cultures treated with the cannabinoids also were deficient in their ability to produce interleukin 1 on appropriate stimulation with bacterial LPS. Spleen cells capable of producing antibody to sheep erythrocytes when stimulated with this antigen in vitro were markedly affected when treated with graded doses of THC or 11-OH THC. Furthermore, the blastogenic responsiveness of normal mouse splenocytes to the T-cell mitogens Con A and PHA as well as the B-cell mitogen E. coli LPS was markedly suppressed by graded concentrations of the cannabinoids in doses that did not affect the viability of the cells. Natural killer cell activity of normal mouse spleen cells was also markedly inhibited by THC and 11-OH THC. Similarly, these cannabinoids suppressed the blastogenic responsiveness and NK activity of human peripheral blood leukocytes from normal individuals. The ability of mouse spleen cells to produce interferon on in vitro stimulation was also suppressed by THC. In addition, injection of THC into mice suppressed blastogenic responsiveness of spleen cells, NK activity, and the production of interferon by lymphoid cells. Thus, it was apparent that these cannabinoids had immunomodulatory effects, both in vivo and in vitro, at noncytotoxic small doses and impaired the ability of the lymphoid cells to express immune function necessary for antiviral resistance.

Spastic long-lasting reflexes in the awake rat after sacral spinal cord injury.

PubMed

Bennett, D J; Sanelli, L; Cooke, C L; Harvey, P J; Gorassini, M A

2004-05-01

Following chronic sacral spinal cord transection in rats the affected tail muscles exhibit marked spasticity, with characteristic long-lasting tail spasms evoked by mild stimulation. The purpose of the present paper was to characterize the long-lasting reflex seen in tail muscles in response to electrical stimulation of the tail nerves in the awake spastic rat, including its development with time and relation to spasticity. Before and after sacral spinal transection, surface electrodes were placed on the tail for electrical stimulation of the caudal nerve trunk (mixed nerve) and for recording EMG from segmental tail muscles. In normal and acute spinal rats caudal nerve trunk stimulation evoked little or no EMG reflex. By 2 wk after injury, the same stimulation evoked long-lasting reflexes that were 1) very low threshold, 2) evoked from rest without prior EMG activity, 3) of polysynaptic latency with >6 ms central delay, 4) about 2 s long, and 5) enhanced by repeated stimulation (windup). These reflexes produced powerful whole tail contractions (spasms) and developed gradually over the weeks after the injury (< or =52 wk tested), in close parallel to the development of spasticity. Pure low-threshold cutaneous stimulation, from electrical stimulation of the tip of the tail, also evoked long-lasting spastic reflexes, not seen in acute spinal or normal rats. In acute spinal rats a strong C-fiber stimulation of the tip of the tail (20 x T) could evoke a weak EMG response lasting about 1 s. Interestingly, when this C-fiber stimulation was used as a conditioning stimulation to depolarize the motoneuron pool in acute spinal rats, a subsequent low-threshold stimulation of the caudal nerve trunk evoked a 300-500 ms long reflex, similar to the onset of the long-lasting reflex in chronic spinal rats. A similar conditioned reflex was not seen in normal rats. Thus there is an unusually long low-threshold polysynaptic input to the motoneurons (pEPSP) that is normally inhibited by descending control. This pEPSP is released from inhibition immediately after injury but does not produce a long-lasting reflex because of a lack of motoneuron excitability. With chronic injury the motoneuron excitability is increased markedly, and the pEPSP then triggers sustained motoneuron discharges associated with long-lasting reflexes and muscle spasms.

Distributive justice and cognitive enhancement in lower, normal intelligence.

PubMed

Dunlop, Mikael; Savulescu, Julian

2014-01-01

There exists a significant disparity within society between individuals in terms of intelligence. While intelligence varies naturally throughout society, the extent to which this impacts on the life opportunities it affords to each individual is greatly undervalued. Intelligence appears to have a prominent effect over a broad range of social and economic life outcomes. Many key determinants of well-being correlate highly with the results of IQ tests, and other measures of intelligence, and an IQ of 75 is generally accepted as the most important threshold in modern life. The ability to enhance our cognitive capacities offers an exciting opportunity to correct disabling natural variation and inequality in intelligence. Pharmaceutical cognitive enhancers, such as modafinil and methylphenidate, have been shown to have the capacity to enhance cognition in normal, healthy individuals. Perhaps of most relevance is the presence of an 'inverted U effect' for most pharmaceutical cognitive enhancers, whereby the degree of enhancement increases as intelligence levels deviate further below the mean. Although enhancement, including cognitive enhancement, has been much debated recently, we argue that there are egalitarian reasons to enhance individuals with low but normal intelligence. Under egalitarianism, cognitive enhancement has the potential to reduce opportunity inequality and contribute to relative income and welfare equality in the lower, normal intelligence subgroup. Cognitive enhancement use is justifiable under prioritarianism through various means of distribution; selective access to the lower, normal intelligence subgroup, universal access, or paradoxically through access primarily to the average and above average intelligence subgroups. Similarly, an aggregate increase in social well-being is achieved through similar means of distribution under utilitarianism. In addition, the use of cognitive enhancement within the lower, normal intelligence subgroup negates, or at the very least minimises, several common objections to cognitive enhancement. Subsequently, this paper demonstrates that there is a compelling case for cognitive enhancement use in individuals with lower, normal intelligence.

Characterization method for relative Raman enhancement for surface-enhanced Raman spectroscopy using gold nanoparticle dimer array

NASA Astrophysics Data System (ADS)

Sugano, Koji; Ikegami, Kohei; Isono, Yoshitada

2017-06-01

In this paper, a characterization method for Raman enhancement for highly sensitive and quantitative surface-enhanced Raman spectroscopy (SERS) is reported. A particle dimer shows a marked electromagnetic enhancement when the particle connection direction is matched to the polarization direction of incident light. In this study, dimers were arrayed by nanotrench-guided self-assembly for a marked total Raman enhancement. By measuring acetonedicarboxylic acid, the fabricated structures were characterized for SERS depending on the polarization angle against the particle connection direction. This indicates that the fabricated structures cause an effective SERS enhancement, which is dominated by the electromagnetic enhancement. Then, we measured 4,4‧-bipyridine, which is a pesticide material, for quantitative analysis. In advance, we evaluated the enhancement of the particle structure by the Raman measurement of acetonedicarboxylic acid. Finally, we compared the Raman intensities of acetonedicarboxylic acid and 4,4‧-bipyridine. Their intensities showed good correlation. The advantage of this method for previously evaluating the enhancement of the substrate was demonstrated. This developed SERS characterization method is expected to be applied to various quantitative trace analyses of molecules with high sensitivity.

Enhanced effect of gap junction uncouplers on macroscopic electrical properties of reperfused myocardium

PubMed Central

Rodriguez-Sinovas, Antonio; García-Dorado, David; Ruiz-Meana, Marisol; Soler-Soler, Jordi

2004-01-01

Transient inhibition of gap junction (GJ)-mediated communication with heptanol during myocardial reperfusion limits infarct size. However, inhibition of cell coupling in normal myocardium may be arrhythmogenic. The purpose of this study was to test the hypothesis that the consequences of GJ inhibition may be magnified in reperfused myocardium compared with normal tissue, thus allowing the inhibition of GJs in reperfused tissue while only minimally modifying overall macroscopic cell coupling in normal myocardium. Concentration–response curves were defined for the effects of heptanol, 18α-glycyrrhetinic acid, halothane, and palmitoleic acid on conduction velocity, tissue electrical impedance, developed tension and lactate dehydrogenase (LDH) release in normoxically perfused rat hearts (n = 17). Concentrations lacking significant effects on tissue impedance were added during the initial 15 min of reperfusion in hearts submitted to 60 min (n = 43) or 30 min (n = 35) of ischaemia. These concentrations markedly increased myocardial electrical impedance (resistivity and phase angle) in myocardium reperfused after either 30 or 60 min of ischaemia, and reduced reperfusion-induced LDH release after 1 h of ischaemia by 83.6, 57.9, 51.7 and 52.5% for heptanol, 18α-glycyrrhetinic acid, halothane and palmitoleic acid, respectively. LDH release was minimal in hearts submitted to 30 min of ischaemia, independently of group allocation. In conclusion, the present results strongly support the hypothesis that intercellular communication in postischaemic myocardium may be effectively reduced by concentrations of GJ inhibitors affecting only minimally overall electrical impedance in normal myocardium. Reduction of cell coupling during initial reperfusion was consistently associated with attenuated lethal reperfusion injury. PMID:15218064

Thymidine Phosphorylase is Angiogenic and Promotes Tumor Growth

NASA Astrophysics Data System (ADS)

Moghaddam, Amir; Zhang, Hua-Tang; Fan, Tai-Ping D.; Hu, De-En; Lees, Vivien C.; Turley, Helen; Fox, Stephen B.; Gatter, Kevin C.; Harris, Adrian L.; Bicknell, Roy

1995-02-01

Platelet-derived endothelial cell growth factor was previously identified as the sole angiogenic activity present in platelets; it is now known to be thymidine phosphorylase (TP). The effect of TP on [methyl-^3H]thymidine uptake does not arise from de novo DNA synthesis and the molecule is not a growth factor. Despite this, TP is strongly angiogenic in a rat sponge and freeze-injured skin graft model. Neutralizing antibodies and site-directed mutagenesis confirmed that the enzyme activity of TP is a condition for its angiogenic activity. The level of TP was found to be elevated in human breast tumors compared to normal breast tissue (P < 0.001). Overexpression of TP in MCF-7 breast carcinoma cells had no effect on growth in vitro but markedly enhanced tumor growth in vivo. These data and the correlation of expression in tumors with malignancy identify TP as a target for antitumor strategies.

Beneficial effects of low dose Musa paradisiaca on the semen quality of male Wistar rats.

PubMed

Alabi, A S; Omotoso, Gabriel O; Enaibe, B U; Akinola, O B; Tagoe, C N B

2013-03-01

This study aimed at determining the effects of administration of mature green fruits of Musa paradisiaca on the semen quality of adult male Wistar rats. THE ANIMALS USED FOR THE STUDY WERE GROUPED INTO THREE: the control group, given 2 ml of double distilled water, a low dose group given 500 mg/kg/day and a high dose group given 1000 mg/kg/day of the plantain fruits, which was made into flour, and dissolved in 2 ml of double distilled water for easy oral administration. Significant increment in the semen parameters was noticed in animals that received a lower dose of the plantain flour, but those animals who received the high dose had marked and very significant reduction in sperm cell concentration and percentage of morphologically normal spermatozoa. Musa paradisiaca should be consumed in moderate quantities in order to derive its beneficial effects of enhancing male reproductive functions.

NF-κB regulation of endothelial cell function during LPS-induced toxemia and cancer

PubMed Central

Kisseleva, Tatiana; Song, Li; Vorontchikhina, Marina; Feirt, Nikki; Kitajewski, Jan; Schindler, Christian

2006-01-01

The transcription factor NF-κB is an important regulator of homeostatic growth and inflammation. Although gene-targeting studies have revealed important roles for NF-κB, they have been complicated by component redundancy and lethal phenotypes. To examine the role of NF-κB in endothelial tissues, Tie2 promoter/enhancer–IκBαS32A/S36A transgenic mice were generated. These mice grew normally but exhibited enhanced sensitivity to LPS-induced toxemia, notable for an increase in vascular permeability and apoptosis. Moreover, B16-BL6 tumors grew significantly more aggressively in transgenic mice, underscoring a new role for NF-κB in the homeostatic response to cancer. Tumor vasculature in transgenic mice was extensive and disorganized. This correlated with a marked loss in tight junction formation and suggests that NF-κB plays an important role in the maintenance of vascular integrity and response to stress. PMID:17053836

Breast MR segmentation and lesion detection with cellular neural networks and 3D template matching.

PubMed

Ertaş, Gökhan; Gülçür, H Ozcan; Osman, Onur; Uçan, Osman N; Tunaci, Mehtap; Dursun, Memduh

2008-01-01

A novel fully automated system is introduced to facilitate lesion detection in dynamic contrast-enhanced, magnetic resonance mammography (DCE-MRM). The system extracts breast regions from pre-contrast images using a cellular neural network, generates normalized maximum intensity-time ratio (nMITR) maps and performs 3D template matching with three layers of 12x12 cells to detect lesions. A breast is considered to be properly segmented when relative overlap >0.85 and misclassification rate <0.10. Sensitivity, false-positive rate per slice and per lesion are used to assess detection performance. The system was tested with a dataset of 2064 breast MR images (344slicesx6 acquisitions over time) from 19 women containing 39 marked lesions. Ninety-seven percent of the breasts were segmented properly and all the lesions were detected correctly (detection sensitivity=100%), however, there were some false-positive detections (31%/lesion, 10%/slice).

Differential modulation of global and local neural oscillations in REM sleep by homeostatic sleep regulation

PubMed Central

Kim, Bowon; Kocsis, Bernat; Hwang, Eunjin; Kim, Youngsoo; Strecker, Robert E.; McCarley, Robert W.; Choi, Jee Hyun

2017-01-01

Homeostatic rebound in rapid eye movement (REM) sleep normally occurs after acute sleep deprivation, but REM sleep rebound settles on a persistently elevated level despite continued accumulation of REM sleep debt during chronic sleep restriction (CSR). Using high-density EEG in mice, we studied how this pattern of global regulation is implemented in cortical regions with different functions and network architectures. We found that across all areas, slow oscillations repeated the behavioral pattern of persistent enhancement during CSR, whereas high-frequency oscillations showed progressive increases. This pattern followed a common rule despite marked topographic differences. The findings suggest that REM sleep slow oscillations may translate top-down homeostatic control to widely separated brain regions whereas fast oscillations synchronizing local neuronal ensembles escape this global command. These patterns of EEG oscillation changes are interpreted to reconcile two prevailing theories of the function of sleep, synaptic homeostasis and sleep dependent memory consolidation. PMID:28193862

Suppression of ADH during water immersion in normal man. [antidiuretic hormone

NASA Technical Reports Server (NTRS)

Epstein, M.; Pins, D. S.; Miller, M.

1975-01-01

A study was undertaken to ascertain whether diuresis induced by immersion is medicated by an inhibition of ADH. Immersion resulted in a progressive decrease in ADH excretion from 80.1 + or - 7 (SEM) to 37.3 + or - 6.3 microU/min (P less than 0.025). Cessation of immersion was associated with a marked increase in ADH from 37.3 + or - 6.3 microU/min to 176.6 + or - 72.6 microU/min during the recovery hour (P less than 0.05). Concomitant with these changes, urine osmolality decreased significantly beginning as early as the initial hour of immersion from 1044 + or - 36 to 542 + or - 66 mosmol/kg H2O during the final hour of immersion (P less than 0.001). These findings are consistent with the earlier suggestion that suppression of ADH release contributes to enhanced free water clearance in hydrated subjects undergoing immersion.

EZH2 in Bladder Cancer, a Promising Therapeutic Target

PubMed Central

Martínez-Fernández, Mónica; Rubio, Carolina; Segovia, Cristina; López-Calderón, Fernando F.; Dueñas, Marta; Paramio, Jesús M.

2015-01-01

Bladder Cancer (BC) represents a current clinical and social challenge. The recent studies aimed to describe the genomic landscape of BC have underscored the relevance of epigenetic alterations in the pathogenesis of these tumors. Among the epigenetic alterations, histone modifications occupied a central role not only in cancer, but also in normal organism homeostasis and development. EZH2 (Enhancer of Zeste Homolog 2) belongs to the Polycomb repressive complex 2 as its catalytic subunit, which through the trimethylation of H3 (Histone 3) on K27 (Lysine 27), produces gene silencing. EZH2 is frequently overexpressed in multiple tumor types, including BC, and plays multiple roles besides the well-recognized histone mark generation. In this review, we summarize the present knowledge on the oncogenic roles of EZH2 and its potential use as a therapeutic target, with special emphasis on BC pathogenesis and management. PMID:26580594

Molecular mechanism of sarcopenia and cachexia: recent research advances.

PubMed

Sakuma, Kunihiro; Aoi, Wataru; Yamaguchi, Akihiko

2017-06-01

Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Muscle loss occurs as a consequence of several chronic diseases (cachexia) and normal aging (sarcopenia). Although many negative regulators (atrogin-1, muscle ring finger-1, nuclear factor-kappaB (NF-κB), myostatin, etc.) have been proposed to enhance protein degradation during both sarcopenia and cachexia, the adaptation of these mediators markedly differs within both conditions. Sarcopenia and cachectic muscles have been demonstrated to be abundant in myostatin-linked molecules. The ubiquitin-proteasome system (UPS) is activated during rapid atrophy model (cancer cachexia), but few mediators of the UPS change during sarcopenia. NF-κB signaling is activated in cachectic, but not in sarcopenic, muscle. Recent studies have indicated the age-related defect of autophagy signaling in skeletal muscle, whereas autophagic activation occurs in cachectic muscle. This review provides recent research advances dealing with molecular mediators modulating muscle mass in both sarcopenia and cachexia.

Differential effects of deep brain stimulation on verbal fluency.

PubMed

Ehlen, Felicitas; Schoenecker, Thomas; Kühn, Andrea A; Klostermann, Fabian

2014-07-01

We aimed at gaining insights into principles of subcortical lexical processing. Therefore, effects of deep brain stimulation (DBS) in different target structures on verbal fluency (VF) were tested. VF was assessed with active vs. inactivated DBS in 13 and 14 patients with DBS in the vicinity of the thalamic ventral intermediate nucleus (VIM) and, respectively, of the subthalamic nucleus (STN). Results were correlated to electrode localizations in postoperative MRI, and compared to those of 12 age-matched healthy controls. Patients' VF performance was generally below normal. However, while activation of DBS in the vicinity of VIM provoked marked VF decline, it induced subtle phonemic VF enhancement in the vicinity of STN. The effects correlated with electrode localizations in left hemispheric stimulation sites. The results show distinct dependencies of VF on DBS in the vicinity of VIM vs. STN. Particular risks for deterioration occur in patients with relatively ventromedial thalamic electrodes. Copyright © 2014 Elsevier Inc. All rights reserved.

Differential modulation of global and local neural oscillations in REM sleep by homeostatic sleep regulation.

PubMed

Kim, Bowon; Kocsis, Bernat; Hwang, Eunjin; Kim, Youngsoo; Strecker, Robert E; McCarley, Robert W; Choi, Jee Hyun

2017-02-28

Homeostatic rebound in rapid eye movement (REM) sleep normally occurs after acute sleep deprivation, but REM sleep rebound settles on a persistently elevated level despite continued accumulation of REM sleep debt during chronic sleep restriction (CSR). Using high-density EEG in mice, we studied how this pattern of global regulation is implemented in cortical regions with different functions and network architectures. We found that across all areas, slow oscillations repeated the behavioral pattern of persistent enhancement during CSR, whereas high-frequency oscillations showed progressive increases. This pattern followed a common rule despite marked topographic differences. The findings suggest that REM sleep slow oscillations may translate top-down homeostatic control to widely separated brain regions whereas fast oscillations synchronizing local neuronal ensembles escape this global command. These patterns of EEG oscillation changes are interpreted to reconcile two prevailing theories of the function of sleep, synaptic homeostasis and sleep dependent memory consolidation.

Development of a novel image-based program to teach narrow-band imaging.

PubMed

Dumas, Cedric; Fielding, David; Coles, Timothy; Good, Norm

2016-08-01

Narrow-band imaging (NBI) is a widely available endoscopic imaging technology; however, uptake of the technique could be improved. Teaching new imaging techniques and assessing trainees' performance can be a challenging exercise during a 1-day workshop. To support NBI training, we developed an online training tool (Medimq) to help experts train novices in NBI bronchoscopy that could assess trainees' performance and provide feedback before the close of the 1-day course. The present study determines whether trainees' capacity to identify relevant pathology increases with the proposed interactive testing method. Two groups of 20 and 18 bronchoscopists have attended an NBI course where they did a pretest and post-test before and after the main lecture, and a follow-up test 4 weeks later to measure retention of knowledge. We measured their ability to mark normal and abnormal 'biopsy size' areas on bronchoscopic NBI images for biopsy. These markings were compared with areas marked by experts on the same images. The first group results were used to pilot the test. After modifications, the results of the improved test for group 2 showed trainees improved by 32% (total class average normalized gain) in detecting normal or abnormal areas. On follow-up testing, Group 2 improved by 23%. The overall class average normalized gain of 32% shows our test can be used to improve trainees' competency in analyzing NBI Images. The testing method (and tool) can be used to measure the follow up 4 weeks later. Better follow-up test results would be expected with more frequent practice by trainees after the course. © The Author(s), 2016.

"A Is for Assessment"... Strategies for A-Level Marking to Motivate and Enable Students of All Abilities to Progress

ERIC Educational Resources Information Center

Facey, Jane

2011-01-01

Jane Facey was unsatisfied with the way in which her A-Level students responded to typical assessment practice. This would normally involve their teacher marking their work and then providing them with written feedback. In looking to move beyond this, Facey drew upon a wide range of research and practice which has sought to develop the way in…

Cutaneous blood flow in psoriasis

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

Klemp, P.; Staberg, B.

1983-12-01

The disappearance rate of /sup 133/Xe was studied in 20 patients with psoriasis vulgaris, using an epicutaneous labeling technique in involved skin lesions or normal-appearing skin of the proximal extensor site of the forearm. Control experiments were performed in 10 normal subjects. Calculations of the cutaneous blood flow (CBF) in psoriatic skin lesions were performed using a tissue-to-blood partition coefficient for /sup 133/Xe, lambda c,pso, of 1.2 ml/100 g/min. lambda c,pso was estimated after the relative content of water, lipids, and proteins had been analyzed in psoriatic skin biopsies of 6 patients with untreated psoriasis. The mean relative content ofmore » water was markedly reduced to 23.5 +/- 1.5% (SEM), and lipids and proteins were markedly increased to 2.5 +/- 0.7% and 74.0 +/- 2.2, respectively, compared to previously published data for normal skin (water 72.5%, lipids 1%, proteins 26.5%). Mean CBF in untreated psoriatic skin was 63.5 +/- 9.0 ml/100 g/min. This was significantly higher than the mean CBF in 10 normal subjects, 6.3 +/- 0.5 ml/100 g/min (p much less than 0.0001). Mean CBF in normal-appearing skin in patients with psoriasis was 11.0 +/- 1.3 ml/100 g/min. This was significantly higher than CBF in normal subjects (p less than 0.0002).« less

Effects of Selective Checkpoint Kinase 1 Inhibition on Cytarabine Cytotoxicity in Acute Myelogenous Leukemia Cells in Vitro

PubMed Central

Schenk, Erin L.; Koh, Brian D.; Flatten, Karen S.; Peterson, Kevin L.; Parry, David; Hess, Allan D.; Smith, B. Douglas; Karp, Judith E.; Karnitz, Larry M.; Kaufmann, Scott H.

2012-01-01

Purpose Previous studies have demonstrated that the replication checkpoint, which involves the kinases ATR and Chk1, contributes to cytarabine resistance in cell lines. In the present study, we examined whether this checkpoint is activated in clinical AML during cytarabine infusion in vivo and then assessed the impact of combining cytarabine with the recently described Chk1 inhibitor SCH 900776 in vitro. Experimental design AML marrow aspirates harvested before and during cytarabine infusion were examined by immunoblotting. Human AML lines treated with cytarabine in the absence or presence of SCH 900776 were assayed for checkpoint activation by immunoblotting, nucleotide incorporation into DNA and flow cytometry. Long-term effects in AML lines, clinical AML isolates, and normal myeloid progenitors were assayed using clonogenic assays. Results Immunoblotting demonstrated increased Chk1 phosphorylation, a marker of checkpoint activation, in over half of Chk1-containing AMLs after 48 h of cytarabine infusion. In human AML lines, SCH 900776 not only disrupted cytarabine-induced Chk1 activation and S phase arrest, but also markedly increased cytarabine-induced apoptosis. Clonogenic assays demonstrated that SCH 900776 enhanced the anti-proliferative effects of cytarabine in AML cell lines and clinical AML samples at concentrations that had negligible impact on normal myeloid progenitors. Conclusions These results not only provide evidence for cytarabine-induced S phase checkpoint activation in AML in the clinical setting, but also show that a selective Chk1 inhibitor can overcome the S phase checkpoint and enhance the cytotoxicity of cytarabine. Accordingly, further investigation of the cytarabine/SCH 900776 combination in AML appears warranted. PMID:22869869

Unbound (bioavailable) IGF1 enhances somatic growth

PubMed Central

Elis, Sebastien; Wu, Yingjie; Courtland, Hayden-William; Cannata, Dara; Sun, Hui; Beth-On, Mordechay; Liu, Chengyu; Jasper, Hector; Domené, Horacio; Karabatas, Liliana; Guida, Clara; Basta-Pljakic, Jelena; Cardoso, Luis; Rosen, Clifford J.; Frystyk, Jan; Yakar, Shoshana

2011-01-01

SUMMARY Understanding insulin-like growth factor-1 (IGF1) biology is of particular importance because, apart from its role in mediating growth, it plays key roles in cellular transformation, organ regeneration, immune function, development of the musculoskeletal system and aging. IGF1 bioactivity is modulated by its binding to IGF-binding proteins (IGFBPs) and the acid labile subunit (ALS), which are present in serum and tissues. To determine whether IGF1 binding to IGFBPs is necessary to facilitate normal growth and development, we used a gene-targeting approach and generated two novel knock-in mouse models of mutated IGF1, in which the native Igf1 gene was replaced by Des-Igf1 (KID mice) or R3-Igf1 (KIR mice). The KID and KIR mutant proteins have reduced affinity for the IGFBPs, and therefore present as unbound IGF1, or ‘free IGF1’. We found that both KID and KIR mice have reduced serum IGF1 levels and a concomitant increase in serum growth hormone levels. Ternary complex formation of IGF1 with the IGFBPs and the ALS was markedly reduced in sera from KID and KIR mice compared with wild type. Both mutant mice showed increased body weight, body and bone lengths, and relative lean mass. We found selective organomegaly of the spleen, kidneys and uterus, enhanced mammary gland complexity, and increased skeletal acquisition. The KID and KIR models show unequivocally that IGF1-complex formation with the IGFBPs is fundamental for establishing normal body and organ size, and that uncontrolled IGF bioactivity could lead to pathological conditions. PMID:21628395

Visual Arrestin 1 Acts as a Modulator for N-Ethylmaleimide Sensitive Factor in the Photoreceptor Synapse

PubMed Central

Huang, Shun-Ping; Brown, Bruce M.; Craft, Cheryl M.

2010-01-01

In the G-protein coupled receptor (GPCR) phototransduction cascade, visual Arrestin1 (Arr1) binds to and deactivates phosphorylated light-activated opsins, a process that is critical for effective recovery and normal vision. In this report, we discovered a novel synaptic interaction between Arr1 and N-ethylmaleimide sensitive factor (NSF) that is enhanced in a dark environment when mouse photoreceptors are depolarized and the rate of exocytosis is elevated. In the photoreceptor synapse, NSF functions to sustain a higher rate of exocytosis, in addition to the compensatory endocytosis to retrieve and to recycle vesicle membrane and synaptic proteins. Not only does Arr1 bind to the junction of NSF N-terminal and its first ATPase domains in an ATP-dependent manner in vitro, but Arr1 also enhances both NSF ATPase and NSF disassembly activities. In vivo experiments in mouse retinas with the Arr1 gene knocked out, the expression levels of NSF and other synapse-enriched components, including vesicular glutamate transporter 1 (vGLUT1), excitatory amino acid transporter 5 (EAAT5), and vesicle associated membrane protein 2 (VAMP2), are markedly reduced, which lead to a substantial decrease in the exocytosis rate with FM1-43. Thus, we propose that the Arr1 and NSF interaction is important for modulating normal synaptic function in mouse photoreceptors. This study demonstrates a vital alternative function for Arr1 in the photoreceptor synapse and provides key insights into the potential molecular mechanisms of inherited retinal diseases, such as Oguchi disease and Arr1-associated retinitis pigmentosa. PMID:20631167

Postnatal Ablation of POMC Neurons Induces an Obese Phenotype Characterized by Decreased Food Intake and Enhanced Anxiety-Like Behavior

PubMed Central

Greenman, Yona; Drori, Yonat; Asa, Sylvia L.; Navon, Inbal; Forkosh, Oren; Gil, Shosh; Stern, Naftali

2013-01-01

Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus are central components of systems regulating appetite and energy homeostasis. Here we report on the establishment of a mouse model in which the ribonuclease III ribonuclease Dicer-1 has been specifically deleted from POMC-expressing neurons (POMCΔDCR), leading to postnatal cell death. Mice are born phenotypically normal, at the expected genetic ratio and with normal hypothalamic POMC-mRNA levels. At 6 weeks of age, no POMC neurons/cells could be detected either in the arcuate nucleus or in the pituitary of POMCΔDCR mice. POMCΔDCR develop progressive obesity secondary to decreased energy expenditure but unrelated to food intake, which was surprisingly lower than in control mice. Reduced expression of AgRP and ghrelin receptor in the hypothalamus and reduced uncoupling protein 1 expression in brown adipose tissue can potentially explain the decreased food intake and decreased heat production, respectively, in these mice. Fasting glucose levels were dramatically elevated in POMCΔDCR mice and the glucose tolerance test revealed marked glucose intolerance in these mice. Secondary to corticotrope ablation, basal and stress-induced corticosterone levels were undetectable in POMCΔDCR mice. Despite this lack of activation of the neuroendocrine stress response, POMCΔDCR mice exhibited an anxiogenic phenotype, which was accompanied with elevated levels of hypothalamic corticotropin-releasing factor and arginine-vasopressin transcripts. In conclusion, postnatal ablation of POMC neurons leads to enhanced anxiety and the development of obesity despite decreased food intake and glucocorticoid deficiency. PMID:23676213

Unbound (bioavailable) IGF1 enhances somatic growth.

PubMed

Elis, Sebastien; Wu, Yingjie; Courtland, Hayden-William; Cannata, Dara; Sun, Hui; Beth-On, Mordechay; Liu, Chengyu; Jasper, Hector; Domené, Horacio; Karabatas, Liliana; Guida, Clara; Basta-Pljakic, Jelena; Cardoso, Luis; Rosen, Clifford J; Frystyk, Jan; Yakar, Shoshana

2011-09-01

Understanding insulin-like growth factor-1 (IGF1) biology is of particular importance because, apart from its role in mediating growth, it plays key roles in cellular transformation, organ regeneration, immune function, development of the musculoskeletal system and aging. IGF1 bioactivity is modulated by its binding to IGF-binding proteins (IGFBPs) and the acid labile subunit (ALS), which are present in serum and tissues. To determine whether IGF1 binding to IGFBPs is necessary to facilitate normal growth and development, we used a gene-targeting approach and generated two novel knock-in mouse models of mutated IGF1, in which the native Igf1 gene was replaced by Des-Igf1 (KID mice) or R3-Igf1 (KIR mice). The KID and KIR mutant proteins have reduced affinity for the IGFBPs, and therefore present as unbound IGF1, or 'free IGF1'. We found that both KID and KIR mice have reduced serum IGF1 levels and a concomitant increase in serum growth hormone levels. Ternary complex formation of IGF1 with the IGFBPs and the ALS was markedly reduced in sera from KID and KIR mice compared with wild type. Both mutant mice showed increased body weight, body and bone lengths, and relative lean mass. We found selective organomegaly of the spleen, kidneys and uterus, enhanced mammary gland complexity, and increased skeletal acquisition. The KID and KIR models show unequivocally that IGF1-complex formation with the IGFBPs is fundamental for establishing normal body and organ size, and that uncontrolled IGF bioactivity could lead to pathological conditions.

Sodium valproate, a histone deacetylase inhibitor, enhances the efficacy of vinorelbine-cisplatin-based chemoradiation in non-small cell lung cancer cells.

PubMed

Gavrilov, Vladimir; Lavrenkov, Konstantin; Ariad, Samuel; Shany, Shraga

2014-11-01

To enhance the anticancer activity of vinorelbine, cisplatin and ionizing radiation (IR) combination against non-small cell lung cancer (NSCLC) cells by co-administration of sodium valproate (VPA), a histone deacetylase inhibitor, and to elucidate molecular events underpinning treatment efficacy. The NSCLC A549 cell line was treated with cisplatin (0.2 μg/ml), vinorelbine (2 nM), VPA (1 mM) and IR (2.5 Gy) alone, or in combination. Cell proliferation, cell-cycle distribution, apoptosis, and levels of DNA double-strand breaks, activated DNA damage checkpoint kinases pCHK1, pCHK2, cell-cycle inhibitors p21CIP1/WAF1 and p27KIP1 were assessed. VPA markedly enhanced the DNA-damaging effect of the cisplatin-vinorelbine-IR combination and induced increased DSBs, and expression of pCHK2, pCHK1, p21CIP1/WAF1 and p27KIP1. These molecular changes led to cell-cycle arrest and increased apoptosis and consequently markedly curtailed cancer cell growth. VPA markedly enhances the anticancer activity of cisplatin-vinorelbine-IR combination. This finding has translational implications for enhancing the efficacy of anticancer treatment and for reducing side-effects by reducing doses of radiation and drugs. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

[Value of combined conventional and contrast enhanced sonography in the evaluation of hepatic disorders].

PubMed

Tranquart, F; Bleuzen, A; Kissel, A

2004-06-01

To assess the value of combined conventional and contrast-material enhanced sonography for the characterization of focal liver lesions. Simultaneous imaging with grey scale and contrast enhanced US was performed in 90 patients following Levovist injection (Schering, Berlin, Germany) using the "Agent Detection Imaging" method (ADI, Siemens-Acuson, Mountain View, USA). US scanning was performed at least 4 minutes after contrast injection with review of both grayscale and contrast enhanced modes. Results for detection and characterization of lesions were compared to the selected gold standard imaging modality (CT or MRI). Final diagnoses included: 20 normal examinations, 41 patients with metastases, 6 patients with hepatocellular carcinoma, 13 patients with hemangioma, 6 patients with other benign lesions, 4 patients with cysts and 6 patients with two types of lesions. Delayed phase contrast enhanced US allowed diagnosis of all lesions except for one metastasis and all hepatocellular carcinomas. While the diagnosis of hepatoma could not be confirmed, the features suggested a malignant etiology. For 7 patients with metastases, more lesions were detected at ADI (4.9 lesions) than at conventional US (1.1 lesion). For 3 patients, CT showed more lesions than ADI US (3.3 versus 1.6 lesions). The accuracy of ADI US for differentiating between benign and malignant lesions was 98.7% compared to 49.6% for conventional US (p<0.001). The total number of lesions detected at ADI US was higher (p<0.01) than at conventional US and not significantly different from that obtained by the gold standard reference methods. Complete characterization was achieved in 92.2% of cases with ADI US compared to 59.2% with conventional US (p<0.001). Contrast-material enhanced US combined with conventional US markedly improves the diagnostic accuracy of US in terms of lesion detection and characterization.

Characterization of renal response to prolonged immersion in normal man

NASA Technical Reports Server (NTRS)

Epstein, M.; Denunzio, A. G.; Ramachandran, M.

1980-01-01

?jDuring the initial phase of space flight, there is a translocation of fluid from the lower parts of the body to the central vascular compartment with a resultant natriuresis, diuresis, and weight loss. Because water immersion is regarded as an appropriate model for studying the redistribution of fluid that occurs in weightlessness, an immersion study of relatively prolonged duration was carried out in order to characterize the temporal profile of the renal adaptation to central hypervolemia. Twelve normal male subjects underwent an immersion study of 8-h duration in the sodium-replete state. Immersion resulted in marked natriuresis and diuresis which were sustained throughout the immersion period. The failure of that natriuresis and diuresis of immersion to abate or cease despite marked extracellular fluid volume contraction as evidenced by a mean weight loss of -2.2 + or - 0.3 kg suggests that central blood volume was not restored to normal and that some degree of central hypervolemia probably persisted.

[School performance of former premature infants in the first four years of school].

PubMed

Frenzel, J; Paalhorn, U

1992-12-01

School achievement during the first four grades was analysed by means of subject marks in 203 prematurely born and in 140 maturely born children. In subjects referring to behaviour in the classroom, no statistically significant differences in average marks could be found between prematurely born children and the control group. The average marks in performance subjects were slightly higher in the subgroup of very prematurely born children. However, statistically significant lower marks were observed in the subject of sports only, and for formerly immature children also in the subject of manual training. The higher the educational level of the mothers, the better the average marks without sports. No relationships between school performance and manifestation of postnatal risk factor like Apgar score, blood gas values and duration of oxygen dependency could be seen. These results demonstrate that school performance of former premature infants lies within the normal variance of their grade.

Alterations in glucose and protein metabolism in animals subjected to simulated microgravity

NASA Technical Reports Server (NTRS)

Mondon, C. E.; Rodnick, K. J.; Azhar, S.; Reaven, G. M.; Dolkas, C. B.

1992-01-01

Reduction of physical activity due to disease or environmental restraints, such as total bed rest or exposure to spaceflight, leads to atrophy of skeletal muscle and is frequently accompanied by alterations in food intake and the concentration of metabolic regulatory hormones such as insulin. Hindlimb suspension of laboratory rats, as a model for microgravity, also shows marked atrophy of gravity-dependent muscles along with a reduced gain in body weight. Suspended rats exhibit enhanced sensitivity to insulin-induced glucose uptake when compared with normal control rats and resistance to insulin action when compared with control rats matched similarly for reduced body weight gain. These changes are accompanied by decreased insulin binding and tyrosine kinase activity in soleus but not plantaris muscle, unchanged glucose uptake by perfused hindlimb and decreased sensitivity but not responsiveness to insulin-induced suppression of net proteolysis in hindlimb skeletal muscle. These findings suggest that loss of insulin sensitivity during muscle atrophy is associated with decreased insulin binding and tyrosine kinase activity in atrophied soleus muscle along with decreased sensitivity to the effects of insulin on suppressing net protein breakdown but not on enhancing glucose uptake by perfused hindlimb.

In vivo effect of human granulocyte-macrophage colony-stimulating factor on megakaryocytopoiesis

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

Aglietta, M.; Monzeglio, C.; Sanavio, F.

1991-03-15

The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on megakaryocytopoiesis and platelet production was investigated in patients with normal hematopoiesis. Three findings indicated that GM-CSF plays a role in megakaryocytopoiesis. During treatment with GM-CSF (recombinant mammalian, glycosylated; Sandoz/Schering-Plough, 5.5 micrograms protein/kg/d, subcutaneously for 3 days) the percentage of megakaryocyte progenitors (megakaryocyte colony forming unit (CFU-Mk)) in S phase (evaluated by the suicide technique with high 3H-Tdr doses) increased from 31% +/- 16% to 88% +/- 11%; and the maturation profile of megakaryocytes was modified, with a relative increase in more immature stage I-III forms. Moreover, by autoradiography (after incubation of marrowmore » cells with 125I-labeled GM-CSF) specific GM-CSF receptors were detectable on megakaryocytes. Nevertheless, the proliferative stimulus induced on the progenitors was not accompanied by enhanced platelet production (by contrast with the marked granulomonocytosis). It may be suggested that other cytokines are involved in the regulation of the intermediate and terminal stages of megakaryocytopoiesis in vivo and that their intervention is an essential prerequisite to turn the GM-CSF-induced proliferative stimulus into enhanced platelet production.« less

Alterations in glucose and protein metabolism in animals subjected to simulated microgravity

NASA Astrophysics Data System (ADS)

Mondon, C. E.; Rodnick, K. J.; Dolkas, C. B.; Azhar, S.; Reaven, G. M.

1992-09-01

Reduction of physical activity due to disease or environmental restraints, such as total bed rest or exposure to spaceflight, leads to atrophy of skeletal muscle and is frequently accompanied by alterations in food intake and the concentration of metabolic regulatory hormones such as insulin. Hindlimb suspension of laboratory rats, as a model for microgravity, also shows marked atrophy of gravity dependent muscles along with a reduced gain in body weight. Suspended rats exhibit enhanced sensitivity to insulin-induced glucose uptake when compared with normal control rats and resistance to insulin action when compared with control rats matched similarly for reduced body weight gain. These changes are accompanied by decreased insulin binding and tyrosine kinase activity in soleus but not plantaris muscle, unchanged glucose uptake by perfused hindlimb and decreased sensitivity but not responsiveness to insulin-induced suppression of net proteolysis in hindlimb skeletal muscle. These findings suggest that loss of insulin sensitivity during muscle atrophy is associated with decreased insulin binding and tyrosine kinase activity in atrophied soleus muscle along with decreased sensitivity to the effects of insulin on suppressing net protein breakdown but not on enhancing glucose uptake by perfused hindlimb.

Plasma Entry from Tail into the Dipolar Magnetosphere During Substorms

NASA Astrophysics Data System (ADS)

Haerendel, Gerhard

Plasma entering the dipolar magnetosphere from the tail has to overcome the obstacle presented by the conductivity enhancements caused by the poleward arc(s). While the arcs move poleward, the plasma proceeds equatorward as testified by the existence of a westward electric field. The arcs break into smaller-scale structures and loops with a tendency of eastward growth and expansion, although the basic driving force is directed earthward/equatorward. The likely reason is that the arc-related conductivity enhancements act as flow barriers and convert normal into shear stresses. The energy derived from the release of the shear stresses and dissipated in the arcs lowers the entropy content of the flux tubes and enables their earthward progression. In addition, poleward jumps of the breakup arcs are quite common. They result from refreshments of the generator plasma by the sequential arrival of flow bursts from the near-Earth neutral line. Once inside the oval, the plasma continues to move equatorward as manifested through north-south aligned auroral forms. Owing to the existence of an inner border of the oval, marked by the Region 2 currents, all flows are eventually diverted sunward.

Cellular senescence of human mammary epithelial cells (HMEC) is associated with an altered MMP-7/HB-EGF signaling and increased formation of elastin-like structures.

PubMed

Bertram, Catharina; Hass, Ralf

2009-10-01

The extracellular matrix (ECM) and a complex interplay of cell-to-cell and cell-to-matrix (ECM) interactions provide important platforms to determine cellular senescence and a potentially tumorigenic transformation of normal human mammary epithelial cells (HMEC). An enhanced formation of extracellular filaments, consisting of elastin-like structures, in senescent post-selection HMEC populations was paralleled by a significantly increased expression of its precursor protein tropoelastin and matched with a markedly elevated activity of the cross-linking enzyme family of lysyl oxidases (LOX). RNAi experiments revealed both the ECM metalloproteinase MMP-7 and the growth factor HB-EGF as potential effectors of an increased tropoelastin expression. Moreover, co-localization of MMP-7 and HB-EGF as well as a concomittant downstream signaling via Fra-1 indicated a possible association between the reduced MMP-7 enzyme activity and an impaired HB-EGF processing, resulting in an enhanced tropoelastin synthesis during senescence of HMEC. In agreement with previous work, these findings suggested an important influence of the extracellular proteinase MMP-7 on the aging process of HMEC, affecting both extracellular remodeling as well as intracellular signaling pathways.

Neonatal olfactory bulbectomy enhances locomotor activity, exploratory behavior and binding of NMDA receptors in pre-pubertal rats.

PubMed

Flores, G; Ibañez-Sandoval, O; Silva-Gómez, A B; Camacho-Abrego, I; Rodríguez-Moreno, A; Morales-Medina, J C

2014-02-14

In this study, we investigated the effect of neonatal olfactory bulbectomy (nOBX) on behavioral paradigms related to olfaction such as exploratory behavior, locomotor activity in a novel environment and social interaction. We also studied the effect of nOBX on the activity of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors during development. The behavioral effects of nOBX (postnatal day 7, PD7) were investigated in pre- (PD30) and post-pubertal (PD60) Wistar rats. NMDA receptor activity was measured with [(125)I]MK-801 in the brain regions associated with the olfactory circuitry. A significant increase in the novelty-induced locomotion was seen in the pre-pubertal nOBX rats. Although the locomotor effect was less marked than in pre-pubertal rats, the nOBX rats tested post-pubertally failed to habituate to the novel situation as quickly as the sham- and normal- controls. Pre-pubertally, the head-dipping behavior was enhanced in nOBX rats compared with sham-operated and normal controls, while normal exploratory behavior was observed between groups in adulthood. In contrast, social interaction was increased in post-pubertal animals that underwent nOBX. Both pre- and post-pubertal nOBX rats recovered olfaction. Interestingly, pre-pubertal rats showed a significant increase in the [(125)I]MK-801 binding in the piriform cortex, dorsal hippocampus, inner and outer layers of the frontal cortex and outer layer of the cingulate cortex. At post-pubertal age, no significant differences in [(125)I]MK-801 binding were observed between groups at any of the brain regions analyzed. These results suggest that nOBX produces pre-pubertal behavioral disturbances and NMDA receptor changes that are transitory with recovery of olfaction early in adulthood. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Hypoxia causes IL-8 secretion, Charcot Leyden crystal formation, and suppression of corticosteroid-induced apoptosis in human eosinophils.

PubMed

Porter, L M; Cowburn, A S; Farahi, N; Deighton, J; Farrow, S N; Fiddler, C A; Juss, J K; Condliffe, A M; Chilvers, E R

2017-06-01

Inflamed environments are typically hypercellular, rich in pro-inflammatory cytokines, and profoundly hypoxic. While the effects of hypoxia on neutrophil longevity and function have been widely studied, little is known about the consequences of this stimulus on eosinophils. We sought to investigate the effects of hypoxia on several key aspects of eosinophil biology, namely secretion, survival, and their sensitivity to glucocorticosteroids (GCS), agents that normally induce eosinophil apoptosis. Eosinophils derived from patients with asthma/atopy or healthy controls were incubated under normoxia and hypoxia, with or without glucocorticoids. Activation was measured by flow cytometry, ELISA of cultured supernatants, and F-actin staining; apoptosis and efferocytosis by morphology and flow cytometry; and GCS efficacy by apoptosis assays and qPCR. Hypoxic incubation (3 kPa) caused (i) stabilization of HIF-2α and up-regulation of hypoxia-regulated genes including BNIP3 (BCL2/adenovirus E1B 19-kDa protein-interacting protein 3) and GLUT1 (glucose transporter 1); (ii) secretion of pre-formed IL-8, and Charcot Leyden crystal (CLC) formation, which was most evident in eosinophils derived from atopic and asthmatic donors; (iii) enhanced F-actin formation; (iv) marked prolongation of eosinophil lifespan (via a NF-κB and Class I PI3-kinase-dependent mechanism); and (v) complete abrogation of the normal pro-apoptotic effect of dexamethasone and fluticasone furoate. This latter effect was evident despite preservation of GCS-mediated gene transactivation under hypoxia. These data indicate that hypoxia promotes an eosinophil pro-inflammatory phenotype by enhancing eosinophil secretory function, delaying constitutive apoptosis, and importantly, antagonizing the normal pro-apoptotic effect of GCS. As eosinophils typically accumulate at sites that are relatively hypoxic, particularly during periods of inflammation, these findings may have important implications to understanding the behaviour of these cells in vivo. © 2016 John Wiley & Sons Ltd.

Roadway Marking Optics for Autonomous Vehicle Guidance and Other Machine Vision Applications

NASA Astrophysics Data System (ADS)

Konopka, Anthony T.

This work determines optimal planar geometric light source and optical imager configurations and electromagnetic wavelengths for maximizing the reflected signal intensity when using machine vision technology to image roadway markings with embedded spherical glass beads. It is found through a first set of experiments that roadway marking samples exhibiting little or no bead rolling effects are uniformly reflective with respect to the azimuthal angle of observation when measured for retroreflectivity within industry standard 30-meter geometry. A second set of experiments indicate that white roadway markings exhibit higher reflectivity throughout the visible spectrum than yellow roadway markings. A roadway marking optical model capable of being used to determine optimal geometric light source and optical imager configurations for maximizing the reflected signal intensities of roadway marking targets is constructed and simulated using optical engineering software. It is found through a third set of experiments that high signal intensities can be measured when the polar angles of the light source and optical imager along a plane normal to a roadway marking are equal, with the maximum signal intensity being measured when the polar angles of both the light source and optical imager are 90°.

Correlative transmission electron microscopy and electrical properties study of switchable phase-change random access memory line cells

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

Oosthoek, J. L. M.; Kooi, B. J., E-mail: B.J.Kooi@rug.nl; Voogt, F. C.

2015-02-14

Phase-change memory line cells, where the active material has a thickness of 15 nm, were prepared for transmission electron microscopy (TEM) observation such that they still could be switched and characterized electrically after the preparation. The result of these observations in comparison with detailed electrical characterization showed (i) normal behavior for relatively long amorphous marks, resulting in a hyperbolic dependence between SET resistance and SET current, indicating a switching mechanism based on initially long and thin nanoscale crystalline filaments which thicken gradually, and (ii) anomalous behavior, which holds for relatively short amorphous marks, where initially directly a massive crystalline filament ismore » formed that consumes most of the width of the amorphous mark only leaving minor residual amorphous regions at its edges. The present results demonstrate that even in (purposely) thick TEM samples, the TEM sample preparation hampers the probability to observe normal behavior and it can be debated whether it is possible to produce electrically switchable TEM specimen in which the memory cells behave the same as in their original bulk embedded state.« less

Correlative transmission electron microscopy and electrical properties study of switchable phase-change random access memory line cells

NASA Astrophysics Data System (ADS)

Oosthoek, J. L. M.; Voogt, F. C.; Attenborough, K.; Verheijen, M. A.; Hurkx, G. A. M.; Gravesteijn, D. J.; Kooi, B. J.

2015-02-01

Phase-change memory line cells, where the active material has a thickness of 15 nm, were prepared for transmission electron microscopy (TEM) observation such that they still could be switched and characterized electrically after the preparation. The result of these observations in comparison with detailed electrical characterization showed (i) normal behavior for relatively long amorphous marks, resulting in a hyperbolic dependence between SET resistance and SET current, indicating a switching mechanism based on initially long and thin nanoscale crystalline filaments which thicken gradually, and (ii) anomalous behavior, which holds for relatively short amorphous marks, where initially directly a massive crystalline filament is formed that consumes most of the width of the amorphous mark only leaving minor residual amorphous regions at its edges. The present results demonstrate that even in (purposely) thick TEM samples, the TEM sample preparation hampers the probability to observe normal behavior and it can be debated whether it is possible to produce electrically switchable TEM specimen in which the memory cells behave the same as in their original bulk embedded state.

The hyperthermia-enhanced association between tropoelastin and its 67-kDa chaperone results in better deposition of elastic fibers.

PubMed

Murphy, Brooke A; Bunda, Severa; Mitts, Thomas; Hinek, Aleksander

2010-12-17

The results of our in vitro experiments indicate that exposing cultured human aortic smooth muscle cells and dermal fibroblasts to 39 to 41 °C induces a significant up-regulation in the net deposition of elastic fibers, but not of collagen I or fibronectin, and also decreases the deposition of chondroitin sulfate-containing moieties. We further demonstrate that mild hyperthermia also rectifies the insufficient elastogenesis notable in cultures of fibroblasts derived from the stretch-marked skin of adult patients and in cultures of dermal fibroblasts from children with Costello syndrome, which is characterized by the accumulation of chondroitin 6-sulfate glycosaminoglycans that induce shedding and inactivation of the 67-kDa elastin-binding protein. We have previously established that this protein serves as a reusable chaperone for tropoelastin and that its recycling is essential for the normal deposition of elastic fibers. We now report that hyperthermia not only inhibits deposition of chondroitin 6-sulfate moieties and the consequent preservation of elastin-binding protein molecules but also induces their faster recycling. This, in turn, triggers a more efficient preservation of tropoelastin, enhancement of its secretion and extracellular assembly into elastic fibers. The presented results encourage using mild hyperthermia to restore elastic fiber production in damaged adult skin and to enhance elastogenesis in children with genetic elastinopathies.

Forest fire weather and computed fire occurrence in western Oregon and western Washington.

Treesearch

Owen P. Cramer

1959-01-01

Severity of the 1959 fire season varied from well below normal in western Washington to a record-setting high in southwestern Oregon. The season was characterized by well-distributed, short rainy periods separated by comparatively short dry spells that frequently included days of high fire danger. July was the only month with markedly above-normal temperatures, and...

Are Prescription Stimulants "Smart Pills"? The Epidemiology and Cognitive Neuroscience of Prescription Stimulant Use by Normal Healthy Individuals

ERIC Educational Resources Information Center

Smith, M. Elizabeth; Farah, Martha J.

2011-01-01

Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience…

[Primary chronic polyarthritis with kidney involvement (mesangiocapillary glomerulonephritis)].

PubMed

Bürkle, P A

1979-01-01

A 34 year old white male patient suffering from seropositive "probable" rheumatoid arthritis developed a severe hypocomplementemic mesangiocapillary glomerulo-nephritis. Rheumatoid factors (Latex test, Waaler-Rose titer) and IgM were markedly elevated in the serum. The third component of complement (C3) was markedly depressed, while the fourth component (C4) was within normal range. The rapid progression of the disease forced us to start an immunosuppressive drug therapy using azathioprine and steroids. Despite marked clinical improvement, e.g. normalisation of complement components, renal function, the disappearance of rheumatoid factor and proteinuria, the second biopsy taken two years later showed unchanged histological and immuno-histological changes of the glomerula.

Effects of vasopressin administration on diuresis of water immersion in normal humans

NASA Technical Reports Server (NTRS)

Epstein, M.; Denunzio, A. G.; Loutzenhiser, R. D.

1981-01-01

The influence of vasopressin suppression on the diuresis encountered during water immersion is investigated in studies on normal humans immersed to the neck. Six hydrated male subjects were studied on two occasions while undergoing 6 h of immersion without or during the administration of aqueous vasopressin for the initial 4 h. Neck immersion is found to result in a significant increase in urinary flow rate beginning in the first hour and persisting throughout the immersion. The administration of vasopressin markedly attenuated the diuretic response throughout the period of infusion, while cessation of vasopressin administration during the final 2 h of immersion resulted in a marked offset of the antidiuresis. Results thus support the view that the suppression of antidiuretic hormone contributes to the immersion diuresis of hydrated subjects.

Smart gated magnetic silica mesoporous particles for targeted colon drug delivery: New approaches for inflammatory bowel diseases treatment.

PubMed

Teruel, Adrián H; Pérez-Esteve, Édgar; González-Álvarez, Isabel; González-Álvarez, Marta; Costero, Ana M; Ferri, Daniel; Parra, Margarita; Gaviña, Pablo; Merino, Virginia; Martínez-Mañez, Ramón; Sancenón, Félix

2018-07-10

Magnetic mesoporous silica microparticles were loaded with safranin O (S1) and with hydrocortisone (S2) and the outer surface functionalized with a bulky azo derivative bearing urea moieties. Aqueous suspensions of both solids at pH 7.4 showed negligible payload release whereas a marked delivery was observed in the presence of sodium dithionite due to the rupture of the azo bonds. Besides, a moderate cargo release was observed at acidic pH due to the hydrolysis of the urea bonds that linked the azo derivative onto the external surface of the inorganic scaffolds. In vitro digestion models showed that S1 and S2 microparticles could be used for the controlled release of payload in the reducing colon environment (in which azoreductase enzymes are present). On the other hand, in vivo pharmacokinetic studies in rats showed that safranine O release from S1 microparticles was concentrated in colon. The performance of S2 microparticles for the treatment of colitis in rats (induced by oral administration of a 2,4,6-trinitrobenzenesulfonic acid solution) was tested. The controlled release of hydrocortisone from S2 in the colon of injured rats induced marked reduction in colon/body weight ratio and in clinical activity score. Also, histological studies showed a marked decrease in inflammation followed by intensive regeneration and almost normal mucosal structure of the individuals treated with S2. Besides, the use of a magnetic belt increased the therapeutic performances of S2 due to an enhanced retention time of the particles in the colon. Copyright © 2018 Elsevier B.V. All rights reserved.

Anti-lipoteichoic acid antibodies enhance release of cytokines by monocytes sensitized with lipoteichoic acid.

PubMed Central

Mancuso, G; Tomasello, F; Ofek, I; Teti, G

1994-01-01

Lipoteichoic acid (LTA) from gram-positive bacteria can stimulate monocytes to produce cytokines. To ascertain whether aggregation of LTA receptors can contribute to this effect, human monocytes were sensitized with LTA from Streptococcus pyogenes, washed, and treated with anti-LTA antibodies. The addition of anti-LTA antibodies or F(ab')2 fragments markedly enhanced the aggregation of LTA receptors, as evidenced by indirect immunofluorescence and the release of tumor necrosis factor alpha and interleukin-1 beta. These findings suggest that aggregation of LTA receptors of monocytes is required for triggering marked cytokine responses. PMID:8132355

The Judgement Processes Involved in the Moderation of Teacher-Assessed Projects

ERIC Educational Resources Information Center

Crisp, Victoria

2017-01-01

Classroom-based assessments have the potential to enhance validity by facilitating the assessment of important skills that are difficult to assess in written examinations. Such assessments tend to be marked by teachers. To ensure consistent marking standards, quality assurance procedures are needed. In the context of continued debate over the…

Enhanced magneto-optical imaging of internal stresses in the removed surface layer

NASA Astrophysics Data System (ADS)

Agalidi, Yuriy; Kozhukhar, Pavlo; Levyi, Sergii; Turbin, Dmitriy

2015-10-01

The paper describes a software method of reconstructing the state of the removed surface layer by visualising internal stresses in the underlying layers of the sample. Such a problem typically needs to be solved as part of forensic investigation that aims to reveal original marking of a sample with removed surface layer. For example, one may be interested in serial numbers of weapons or vehicles that had the surface layer of metal removed from the number plate. Experimental results of studying gradient internal stress fields in ferromagnetic sample using the NDI method of magneto-optical imaging (MOI) are presented. Numerical modelling results of internal stresses enclosed in the surface marking region are analysed and compared to the experimental results of magneto-optical imaging (MOI). MOI correction algorithm intended for reconstructing internal stress fields in the removed surface layer by extracting stresses retained by the underlying layers is described. Limiting ratios between parameters of a marking font are defined for the considered correction algorithm. Enhanced recognition properties for hidden stresses left by marking symbols are experimentally verified and confirmed.

The phototoxicity of vemurafenib: An investigation of clinical monochromator phototesting and in vitro phototoxicity testing.

PubMed

Woods, J A; Ferguson, J S; Kalra, S; Degabriele, A; Gardner, J; Logan, P; Ferguson, J

2015-10-01

Vemurafenib is a targeted therapy approved for the treatment of patients with metastatic melanoma harbouring the BRAF V600E mutation. Photosensitivity has been reported in over 50% of patients and has been demonstrated to involve at least the broadband UVA spectrum in most patients. Erythrocyte protoporphyrin levels have also been reported as elevated in some patients. We report the results of monochromator phototesting in one patient recorded before and while taking vemurafenib. Analysis of porphyrin levels was also conducted. After one month of vemurafenib therapy the patient demonstrated markedly increased light sensitivity in the UVA spectrum between 335 ± 27 nm, 365 ± 27 nm and 400 ± 27 nm. However responses in the UVB (305 ± 5 nm) and blue light (430 ± 27 nm) regions were normal. There was no abnormal immediate erythemal response. Pre-vemurafenib baseline phototesting was normal, as was repeat testing two months later when the patient was taking high doses of systemic steroid. No abnormal porphyrins were detected and the antinuclear antibody test was normal. In parallel studies, HaCaT keratinocytes incubated with vemurafenib were killed by UVA but not by visible (blue) light and did not show evidence of detectable intracellular porphyrin in the presence of the drug. These data confirm vemurafenib induced UVA photosensitivity with a probable phototoxic mechanism not mediated via enhanced porphyrin. Copyright © 2015 Elsevier B.V. All rights reserved.

Anti-angiogenic therapy with contrast-enhanced ultrasound in colorectal cancer patients with liver metastasis.

PubMed

Wu, Zhiyong; Yang, Xiaowei; Chen, Li; Wang, Zhikuan; Shi, Yan; Mao, Hui; Dai, Guanghai; Yu, Xiaoling

2017-05-01

The aim of the study was to evaluate the efficacy of anti-angiogenic therapy with dynamic contrast-enhanced ultrasound (DCE-US) in colorectal cancer (CRC) patients with liver metastasis.A total of 50 CRC patients with liver metastasis who received bevacizumab (BEV)-based chemotherapy (BEV + FOLFOX6 protocol) were recruited into the present study. Before the study (d0), and 3, 7, 14, and 42 days (d3, d7, d14, and d42) after chemotherapy, DCE-US was performed, and tumor perfusion was evaluated quantitatively by retention time (RT), peak enhancement (PE), and wash-in area under the curve (WiAUC) on the basis of a contrast-uptake curve determined with original linear data.Routine ultrasonography was used to evaluate metastatic foci in the liver at baseline. A metastatic focus was selected for dynamic monitoring with ultrasound. The metastatic foci were 1.5 to 8 cm (median: 2.5 cm). The results of hemodynamics monitored at different time points, including RT, PE, and WiAUC, showed that RT at baseline was significantly different between groups (P < .001; Responder group: 10.54 seconds; nonresponder group: 15.33 seconds). The2 groups had opposite changes in RT (continuous increase in the responder group and transient reduction in the nonresponder). The RT of metastatic foci was normalized to that of adjacent normal liver as standard RT-quotient, a similar trend was observed, and no marked difference was noted in the standard RT-quotient between the 2 groups. The median progression-free survival was significantly higher in the increased-RT group (10.8 months) than the decreased-RT group (2.5 months) (P = .002). There were no significant differences in peak intensity and WiAUC between the 2 groups.DCE-US can be used to quantitatively evaluate the hemodynamics of liver metastasis in CRC patients who received bevacizumab-based chemotherapy.

High glucose-boosted inflammatory responses to lipopolysaccharide are suppressed by statin.

PubMed

Nareika, A; Maldonado, A; He, L; Game, B A; Slate, E H; Sanders, J J; London, S D; Lopes-Virella, M F; Huang, Y

2007-02-01

It has been established that periodontal diseases are more prevalent and of greater severity in diabetic patients than in nondiabetic patients. Recent studies have underscored the role of monocytes and macrophages in periodontal tissue inflammation and destruction in diabetic patients. Although it has been shown that monocytes isolated from diabetic patients produce more inflammatory cytokines and that gingival crevicular fluid collected from diabetic patients contains higher levels of inflammatory cytokines than that obtained from nondiabetic patients, the underlying mechanisms are not well understood. U937 histiocytes cultured in medium containing either normal (5 mM) or high (25 mM) glucose were treated with 100 ng/ml of lipopolysaccharide for 24h. After the treatment, cytokines in the medium and cytokine mRNA in the cells were quantified using enzyme-linked immunosorbet assay and real-time polymerase chain reaction, respectively. In this study, we demonstrated that the pre-exposure of U937 histiocytes to high glucose concentrations markedly increased the lipopolysaccharide-induced secretion of pro-inflammatory cytokines and chemokines and the cellular inducible nitric oxide level compared with pre-exposure to normal glucose. Our data also showed that the increased secretion of cytokines was a result of increased mRNA expression. Furthermore, the effects of statin and peroxisome proliferators-activated receptor agonists on high glucose-enhanced secretion of cytokines were determined. The results showed that simvastatin, but not fenofibrate or pioglitazone, inhibited high glucose-enhanced cytokine release. This study has shown that high glucose concentrations and lipopolysaccharide act synergistically to stimulate the secretion of inflammatory mediators, and that statin is capable of suppressing the high glucose-boosted proinflammatory response. This study therefore delineates a novel mechanism by which hyperglycemia enhances the inflammatory responses of macrophages and suggests that statin may be useful in the treatment of periodontal disease in diabetic patients.

Heart rate and blood pressure variabilities in salt-sensitive hypertension.

PubMed

Piccirillo, G; Bucca, C; Durante, M; Santagada, E; Munizzi, M R; Cacciafesta, M; Marigliano, V

1996-12-01

In salt-sensitive hypertension, a high sodium intake causes plasma catecholamines to rise and pulmonary baroreceptor plasticity to fall. In salt-sensitive and salt-resistant hypertensive subjects during low and high sodium intakes, we studied autonomic nervous system activity by power spectral analysis of heart rate and arterial pressure variabilities and baroreceptor sensitivity. In all subjects, high sodium intake significantly enhanced the low-frequency power of heart rate and arterial pressures at rest and after sympathetic stress. It also increased heart rate and arterial pressure variabilities. During high sodium intake, salt-sensitive hypertensive subjects had significantly higher low-frequency powers of systolic arterial pressure (7.5 mm Hg2, P < .05) and of heart rate at rest (59.2 +/- 2.4 normalized units [NU], P < .001) than salt-resistant subjects (6.6 +/- 0.3 mm Hg2, 55.0 +/- 3.2 NU) and normotensive control subjects (5.1 +/- 0.5 mm Hg2, 41.6 +/- 2.9 NU). In salt-sensitive subjects, low sodium intake significantly reduced low-frequency normalized units (P < .001) and the ratio of low- to high-power frequency (P < .001). High-sodium intake significantly increased baroreflex sensitivity in control subjects (from 10.0 +/- 0.7 to 17.5 +/- 0.7 ms/mm Hg, P < .001) and salt-resistant subjects (from 6.9 +/- 0.7 to 13.9 +/- 0.9, P < .05) but not in salt-sensitive subjects (7.4 +/- 0.3 to 7.9 +/- 0.4). In conclusion, a high sodium intake markedly enhances cardiac sympathetic activity in salt-sensitive and salt-resistant hypertension. In contrast, although reduced sodium intake lowers arterial pressure and sympathetic activity, it does so only in salt-sensitive subjects. Hence, in salt-resistant subjects, neither arterial pressure nor sympathetic activity depends on salt intake. During a high sodium intake in normotensive subjects and salt-resistant hypertensive subjects, increased sympathetic activity is probably compensated by enhanced baroreflex sensitivity.

Association of expiratory airway dysfunction with marked obesity in healthy adult dogs.

PubMed

Bach, Jonathan F; Rozanski, Elizabeth A; Bedenice, Daniela; Chan, Daniel L; Freeman, Lisa M; Lofgren, Jennifer L S; Oura, Trisha J; Hoffman, Andrew M

2007-06-01

To evaluate the effects of obesity on pulmonary function in healthy adult dogs. 36 Retrievers without cardiopulmonary disease. Dogs were assigned to 1 of 3 groups on the basis of body condition score (1 through 9): nonobese (score, 4.5 to 5.5), moderately obese (score, 6.0 to 6.5), and markedly obese (score, 7.0 to 9.0). Pulmonary function tests performed in conscious dogs included spirometry and measurement of inspiratory and expiratory airway resistance (R(aw)) and specific R(aw) (sR(aw)) during normal breathing and during hyperpnea via head-out whole-body plethysmography. Functional residual capacity (FRC; measured by use of helium dilution), diffusion capacity of lungs for carbon monoxide (DLCO), and arterial blood gas variables (PaO(2), PaCO(2), and alveolar-arterial gradient) were assessed. During normal breathing, body condition score did not influence airway function, DLCO, or arterial blood gas variables. During hyperpnea, expiratory sR(aw) was significantly greater in markedly obese dogs than nonobese dogs and R(aw) was significantly greater in markedly obese dogs, compared with nonobese and moderately obese dogs. Although not significantly different, markedly obese dogs had a somewhat lower FRC, compared with other dogs. In dogs, obesity appeared to cause airflow limitation during the expiratory phase of breathing, but this was only evident during hyperpnea. This suggests that flow limitation is dynamic and likely occurs in the distal (rather than proximal) portions of the airways. Further studies are warranted to localize the flow-limited segment and understand whether obesity is linked to exercise intolerance via airway dysfunction in dogs.

Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits.

PubMed

Yang, Dun-Sheng; Stavrides, Philip; Mohan, Panaiyur S; Kaushik, Susmita; Kumar, Asok; Ohno, Masuo; Schmidt, Stephen D; Wesson, Daniel; Bandyopadhyay, Urmi; Jiang, Ying; Pawlik, Monika; Peterhoff, Corrinne M; Yang, Austin J; Wilson, Donald A; St George-Hyslop, Peter; Westaway, David; Mathews, Paul M; Levy, Efrat; Cuervo, Ana M; Nixon, Ralph A

2011-01-01

Autophagy, a major degradative pathway for proteins and organelles, is essential for survival of mature neurons. Extensive autophagic-lysosomal pathology in Alzheimer's disease brain contributes to Alzheimer's disease pathogenesis, although the underlying mechanisms are not well understood. Here, we identified and characterized marked intraneuronal amyloid-β peptide/amyloid and lysosomal system pathology in the Alzheimer's disease mouse model TgCRND8 similar to that previously described in Alzheimer's disease brains. We further establish that the basis for these pathologies involves defective proteolytic clearance of neuronal autophagic substrates including amyloid-β peptide. To establish the pathogenic significance of these abnormalities, we enhanced lysosomal cathepsin activities and rates of autophagic protein turnover in TgCRND8 mice by genetically deleting cystatin B, an endogenous inhibitor of lysosomal cysteine proteases. Cystatin B deletion rescued autophagic-lysosomal pathology, reduced abnormal accumulations of amyloid-β peptide, ubiquitinated proteins and other autophagic substrates within autolysosomes/lysosomes and reduced intraneuronal amyloid-β peptide. The amelioration of lysosomal function in TgCRND8 markedly decreased extracellular amyloid deposition and total brain amyloid-β peptide 40 and 42 levels, and prevented the development of deficits of learning and memory in fear conditioning and olfactory habituation tests. Our findings support the pathogenic significance of autophagic-lysosomal dysfunction in Alzheimer's disease and indicate the potential value of restoring normal autophagy as an innovative therapeutic strategy for Alzheimer's disease.

Supplementation of different concentrations of Orvus Es Paste (OEP) to ostrich egg yolk lipoprotein extender improves post-thaw boar semen quality.

PubMed

Fraser, L; Jasiewicz, E; Kordan, W

2014-01-01

This study aimed to compare post-thaw quality of boar semen following freezing in an ostrich egg yolk lipoprotein (LPFo) extender supplemented with 0%, 0.25% and 0.50% Orvus Es Paste (OEP). Sperm assessments included total motility (TMOT), mitochondrial function (MF), plasma membrane integrity (PMI) and acrosome integrity (normal apical ridge, NAR). Considerable variations among boars and OEP treatments had a significant effect (P < 0.001) on post-thaw sperm characteristics. It was observed that post-thaw sperm characteristics were significantly compromised in semen samples frozen in the absence of OEP. By contrast, lactose-LPFo-glycerol extender supplemented with either 0.25% OEP or 0.50% OEP markedly enhanced post-thaw sperm characteristics. In all boars, there were no marked differences in post-thaw sperm TMOT between the freezing extenders supplemented with 0.25% and 0.50% OEP. However, a decline in the percentage of post-thaw motile spermatozoa was more pronounced in the extender supplemented with 0.50% OEP following a 120-min incubation period. Furthermore, the proportions of frozen-thawed spermatozoa with MF, PMI and NAR acrosomes varied significantly among the boars in the OEP-supplemented extenders. The findings of this study indicate that different OEP concentrations, in the presence of ostrich egg yolk lipoproteins, could have varying effects on post-thaw sperm survival.

Blockade of the ERK pathway enhances the therapeutic efficacy of the histone deacetylase inhibitor MS-275 in human tumor xenograft models

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

Sakamoto, Toshiaki; Ozaki, Kei-ichi; Fujio, Kohsuke

2013-04-19

Highlights: •Blockade of the ERK pathway enhances the anticancer efficacy of HDAC inhibitors. •MEK inhibitors sensitize human tumor xenografts to HDAC inhibitor cytotoxicity. •Such the enhanced efficacy is achieved by a transient blockade of the ERK pathway. •This drug combination provides a promising therapeutic strategy for cancer patients. -- Abstract: The ERK pathway is up-regulated in various human cancers and represents a prime target for mechanism-based approaches to cancer treatment. Specific blockade of the ERK pathway alone induces mostly cytostatic rather than pro-apoptotic effects, however, resulting in a limited therapeutic efficacy of the ERK kinase (MEK) inhibitors. We previously showedmore » that MEK inhibitors markedly enhance the ability of histone deacetylase (HDAC) inhibitors to induce apoptosis in tumor cells with constitutive ERK pathway activation in vitro. To evaluate the therapeutic efficacy of such drug combinations, we administered the MEK inhibitor PD184352 or AZD6244 together with the HDAC inhibitor MS-275 in nude mice harboring HT-29 or H1650 xenografts. Co-administration of the MEK inhibitor markedly sensitized the human xenografts to MS-275 cytotoxicity. A dose of MS-275 that alone showed only moderate cytotoxicity thus suppressed the growth of tumor xenografts almost completely as well as induced a marked reduction in tumor cellularity when administered with PD184352 or AZD6244. The combination of the two types of inhibitor also induced marked oxidative stress, which appeared to result in DNA damage and massive cell death, specifically in the tumor xenografts. The enhanced therapeutic efficacy of the drug combination was achieved by a relatively transient blockade of the ERK pathway. Administration of both MEK and HDAC inhibitors represents a promising chemotherapeutic strategy with improved safety for cancer patients.« less

Role of proton magnetic resonance spectroscopy in the diagnosis of gliomatosis cerebri: a unique pattern of normal choline but elevated Myo-inositol metabolite levels.

PubMed

Mohana-Borges, Aurea V R; Imbesi, Steven G; Dietrich, Rosalind; Alksne, John; Amjadi, Darius K

2004-01-01

A patient with histologically proven gliomatosis cerebri presented with a normal choline level but a markedly abnormal elevated myo-inositol level on magnetic resonance (MR) spectroscopy. We describe the case presentation, imaging findings (in particular, the unique MR spectroscopic pattern), and their significance regarding the diagnosis of this relatively rare neoplasm.

Effect of Inflammatory and Noninflammatory Stress on Beta-Hydroxybutyrate and Free Fatty Acids in Rat Blood.

DTIC Science & Technology

fasting plus screen-restraint and fasting plus femoral fracture. Inflammatory stresses caused a marked inhibition of the normal fasting-induced ketosis ...and a reduction in the level of circulating free fatty acids. Noninflammatory stresses caused no inhibition of the normal fasting-induced ketosis but did cause a reduction in the level of circulating free fatty acids. (Author)

33 CFR 183.27 - Construction of markings.

Code of Federal Regulations, 2010 CFR

2010-07-01

... exposure to water, oil, salt spray, direct sunlight, heat, cold, and wear expected in normal operation of...) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Display of Capacity Information § 183.27 Construction of...

33 CFR 183.27 - Construction of markings.

Code of Federal Regulations, 2011 CFR

2011-07-01

... exposure to water, oil, salt spray, direct sunlight, heat, cold, and wear expected in normal operation of...) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Display of Capacity Information § 183.27 Construction of...

Effects of pituitary dwarfism in the mouse on fast and slow skeletal muscles.

PubMed

Stickland, N C; Crook, A R; Sutton, C M

1994-01-01

The Snell dwarf mouse exhibits impaired growth of the anterior pituitary resulting in reduced levels of growth hormone and thyroid stimulating hormone. Ten dwarf mice and 10 phenotypically normal littermates were killed at 33 days of age. M. biceps brachii (a predominantly fast muscle) and m. soleus (a relatively slow muscle) were removed from each animal and complete frozen transverse sections obtained. Serial sections were reacted for various enzyme activities in order to identify muscle fibre types. There was no difference in the total number of muscle fibres in m. biceps brachii but a small difference in m. soleus between normal and dwarf mice. There were marked differences in the size of all fibre types between normal and dwarf mice with the largest differences in m. soleus. The percentage of slow oxidative fibres was similar (about 32%) in both groups of mice for m. soleus but there was a marked difference for this fibre type in m. biceps brachii being about 1.5% in normal mice and 8.0% in dwarf mice. This may be related to a difference in levels of thyroid hormone. Nuclear density was very significantly greater in dwarf muscles although total nuclear numbers were less than in normal muscles. These differences are most likely due to growth hormone levels. Differences in nuclear content were much greater in m. soleus than in m. biceps brachii.

A maximum contraction and substantial quantities of tritium can be obtained from tetraethylammonium-treated [3H]-noradrenaline preloaded, rat vas deferens in response to a single electrical shock.

PubMed Central

Wakade, A. R.

1980-01-01

1 In the normal and phenoxybenzamine-treated vasa deferentia of the rat the overflow of tritium after preloading with [3H]-noradrenaline increased with the increase in frequency of transmural stimulation. Phenozybenzamine enhanced overflow by 5 to 7 fold. 2 After tetraethylammonium (TEA, 10 mM), fractional tritium overflow at 5 Hz increased from a control value of 2.8 to 53 X 10(-4), and at 0.5 Hz it reached 154 X 10(-4). Enhancement of overflow was inversely related to the frequency of stimulation. 3 Contractor responses of the vas deferens induced by transmural stimulation were markedly potentiated, both in amplitude and duration, by 10 mM TEA. The contraction developed in the presence of 10 mM TEA at 0.5 Hz was comparable to that obtained at 10 Hz in normal Krebs solution. 4 In the presence of 5 mM TEA, contractions of the vas deferens caused by exogenous noradrenaline were potentiated about 5 fold. 5 The overflow and contractor response induced by 45 mM K were enhanced about 5 fold in 10 mM TEA-Krebs solution. Facilitation of K-induced overflow by TEA was reduced over 50% by tetrodotoxin (TTX, 1 microM). 6 Delivery of a single shock (1.0 ms duration) to 10 mM TEA-treated vas deferens resulted in a 63% increase in tritium overflow over background overflow. The fractional overflow amounted to almost 720 X 10(-4) after a single shock, as compared to 154 X 10(-4) obtained at 0.5 Hz. 7 The vas deferens treated with 10 mM TEA and stimulated by a single shock developed a contraction which was greater in amplitude and duration than that seen in normal tissue at 10 Hz. 8 Five second serial samples collected from superfused 10 mM TEA-treated vas deferens contained maximum quantities of radioactivity in the first 5 s after a single shock. In subsequent samples, radioactivity gradually declined, and reached prestimulation level after about 25 s. 9 The fractional overflow caused by stimulation at 0.1 Hz in 10 mM TEA-treated tissue progressively increased as external Ca was gradually raised from 0.83 to 10 mM. 10 The mechanism of action of TEA in enhancing the overflow of sympathetic transmitter, particularly in response to a single shock, is discussed in relation to Ca. PMID:7052336

Cardiovascular function in male and female JCR:LA-cp rats: effect of high-fat/high-sucrose diet.

PubMed

Hunter, Ian; Soler, Amanda; Joseph, Gregory; Hutcheson, Brenda; Bradford, Chastity; Zhang, Frank Fan; Potter, Barry; Proctor, Spencer; Rocic, Petra

2017-04-01

Thirty percent of the world population is diagnosed with metabolic syndrome. High-fat/high-sucrose (HF/HS) diet (Western diet) correlates with metabolic syndrome prevalence. We characterized effects of the HF/HS diet on vascular (arterial stiffness, vasoreactivity, and coronary collateral development) and cardiac (echocardiography) function, oxidative stress, and inflammation in a rat model of metabolic syndrome (JCR rats). Furthermore, we determined whether male versus female animals were affected differentially by the Western diet. Cardiovascular function in JCR male rats was impaired versus normal Sprague-Dawley (SD) rats. HF/HS diet compromised cardiovascular (dys)function in JCR but not SD male rats. In contrast, cardiovascular function was minimally impaired in JCR female rats on normal chow. However, cardiovascular function in JCR female rats on the HF/HS diet deteriorated to levels comparable to JCR male rats on the HF/HS diet. Similarly, oxidative stress was markedly increased in male but not female JCR rats on normal chow but was equally exacerbated by the HF/HS diet in male and female JCR rats. These results indicate that the Western diet enhances oxidative stress and cardiovascular dysfunction in metabolic syndrome and eliminates the protective effect of female sex on cardiovascular function, implying that both males and females with metabolic syndrome are at equal risk for cardiovascular disease. NEW & NOTEWORTHY Western diet abolished protective effect of sex against cardiovascular disease (CVD) development in premenopausal animals with metabolic syndrome. Western diet accelerates progression of CVD in male and female animals with preexisting metabolic syndrome but not normal animals. Exacerbation of baseline oxidative stress correlates with accelerated progression of CVD in metabolic syndrome animals on Western diet. Copyright © 2017 the American Physiological Society.

Cardiovascular function in male and female JCR:LA-cp rats: effect of high-fat/high-sucrose diet

PubMed Central

Hunter, Ian; Soler, Amanda; Joseph, Gregory; Hutcheson, Brenda; Bradford, Chastity; Zhang, Frank Fan; Potter, Barry; Proctor, Spencer

2017-01-01

Thirty percent of the world population is diagnosed with metabolic syndrome. High-fat/high-sucrose (HF/HS) diet (Western diet) correlates with metabolic syndrome prevalence. We characterized effects of the HF/HS diet on vascular (arterial stiffness, vasoreactivity, and coronary collateral development) and cardiac (echocardiography) function, oxidative stress, and inflammation in a rat model of metabolic syndrome (JCR rats). Furthermore, we determined whether male versus female animals were affected differentially by the Western diet. Cardiovascular function in JCR male rats was impaired versus normal Sprague-Dawley (SD) rats. HF/HS diet compromised cardiovascular (dys)function in JCR but not SD male rats. In contrast, cardiovascular function was minimally impaired in JCR female rats on normal chow. However, cardiovascular function in JCR female rats on the HF/HS diet deteriorated to levels comparable to JCR male rats on the HF/HS diet. Similarly, oxidative stress was markedly increased in male but not female JCR rats on normal chow but was equally exacerbated by the HF/HS diet in male and female JCR rats. These results indicate that the Western diet enhances oxidative stress and cardiovascular dysfunction in metabolic syndrome and eliminates the protective effect of female sex on cardiovascular function, implying that both males and females with metabolic syndrome are at equal risk for cardiovascular disease. NEW & NOTEWORTHY Western diet abolished protective effect of sex against cardiovascular disease (CVD) development in premenopausal animals with metabolic syndrome. Western diet accelerates progression of CVD in male and female animals with preexisting metabolic syndrome but not normal animals. Exacerbation of baseline oxidative stress correlates with accelerated progression of CVD in metabolic syndrome animals on Western diet. PMID:28087518

Similarities and differences between learning abilities, "pure" learning disabilities, "pure" ADHD and comorbid ADHD with learning disabilities.

PubMed

Mangina, Constantine A; Beuzeron-Mangina, Helen

2009-08-01

This research pursues the crucial question of the differentiation of preadolescents with "Pure" ADHD, comorbid ADHD with learning disabilities, "Pure" learning disabilities and age-matched normal controls. For this purpose, Topographic Mapping of Event-Related Brain Potentials (ERPs) to a Memory Workload Paradigm with visually presented words, Bilateral Electrodermal Activity during cognitive workload and Mangina-Test performance were used. The analysis of Topographic distribution of amplitudes revealed that normal preadolescents were significantly different from "Pure" ADHD (P<0.0001), "Pure" learning disabilities (P<0.0001), and comorbid ADHD with learning disabilities (P<0.0009), by displaying enhanced prefrontal and frontal negativities (N450). In contrast, preadolescents with "Pure" ADHD and comorbid ADHD with learning disabilities have shown a marked reduction of prefrontal and frontal negativities (N450). As for the "Pure" Learning Disabled preadolescents, very small positivities (P450) in prefrontal and frontal regions were obtained as compared to the other pathological groups. Bilateral Electrodermal Activity during cognitive workload revealed a significant main effect for groups (P<0.00001), Left versus Right (P=0.0029) and sessions (P=0.0136). A significant main effect for the Mangina-Test performance which separated the four groups was found (P<0.000001). Overall, these data support the existence of clear differences and similarities between the pathological preadolescent groups as opposed to age-matched normal controls. The psychophysiological differentiation of these groups, provides distinct biological markers which integrate central, autonomic and neuropsychometric variables by targeting the key features of these pathologies for diagnosis and intervention strategies and by providing knowledge for the understanding of normal neurocognitive processes and functions.

Implementation of a Formative Assessment Model Incorporating Peer and Self-Assessment

ERIC Educational Resources Information Center

Orsmond, Paul; Merry, Stephen; Callaghan, Arthur

2004-01-01

This paper reports a study designed to enhance students' ability to implement assessment marking criteria and to develop the role of dialogue in student learning. Pairs or trios of undergraduate biology students were asked to complete a poster on the theme of histology using student/tutor-constructed marking criteria. The study showed: (1)…

Enhanced dispersion of epicardial activation-recovery intervals at sites of histological inhomogeneity during regional cardiac ischaemia and reperfusion

PubMed Central

Gottwald, E; Gottwald, M; Dhein, S

1998-01-01

Objective—To examine how epicardial activation and repolarisation patterns change in the course of ischaemia, and how these changes are related to the underlying histological structures.
Methods—Langendorff perfused isolated rabbit hearts were submitted to 30 minutes of left anterior descending coronary artery occlusion followed by 30 minutes of reperfusion. A 256 channel epicardial map was plotted during the various experimental phases. Activation time points were determined as t(dU/dtmin) and repolarisation time points as t(dU/dtmax). From these data the local activation-recovery interval (ARI), its dispersion (SD of ARI), and the geometry of the activation spread could be analysed. After the experiments the hearts were processed histologically and the mapping data were projected onto histological slides.
Results—There was elevation of the ST segment within the occluded area, which recovered during reperfusion. Within this area, ARI was significantly shortened and its dispersion was maximally enhanced. The enhancement of dispersion was pronounced at sites of histological inhomogeneity like fat, connective tissue, or vessels. There was also a change in the preferential direction of activation spread within the occluded zone with a marked transverse propagation of the activation wavefront, whereas under normal conditions the activation followed the longitudinal fibre axis. In addition, the total activation time in the occluded area was significantly prolonged.
Conclusions—Ischaemia alters the local activation pattern with enhanced dispersion, especially at sites of histological irregularity, transverse shift of the activation waves, and a general slowing of conduction, which may explain the increased susceptibility to arrhythmia in hearts with enhanced histological irregularities—for example, an infarct or in multi-infarcted hearts, or after myocarditis. 

 Keywords: dispersion;  epicardial activation-recovery interval;  ischaemia PMID:9659194

Growth enhancement by embryonic fibroblasts upon cotransplantation of noncommitted pig embryonic tissues with fully committed organs.

PubMed

Cohen, Sivan; Tchorsh-Yutsis, Dalit; Aronovich, Anna; Tal, Orna; Eventov-Friedman, Smadar; Katchman, Helena; Klionsky, Yael; Shezen, Elias; Reisner, Yair

2010-05-27

We recently defined the optimal gestational time windows for the transplantation of several embryonic tissues. We showed that the liver and kidney obtained from E28 pig embryos can grow and differentiate normally after transplantation, whereas 1 week earlier in gestation, these tissues develop into teratoma-like structures or fibrotic mass. In this study, we investigated whether cotransplantation of E28 with E21 tissue could control its tumorogenic potential, or alternatively whether the stem cells derived from the earlier tissue contribute to the growth of the more committed one. Pig embryonic precursors from E21 and E28 gestational age were transplanted alone or together, into nonobese diabetic/severe combined immunodeficiency mice, and their growth and differentiation was evaluated by immunohistology. In situ analysis, based on sex disparity between the E21 and E28 tissues, was used to identify the tissue source. In some experiments, mouse embryonic fibroblasts (MEF) were cotransplanted with E28 liver, and their effect was evaluated. E28 tissues could not abrogate the propensity of the cells within the undifferentiated tissue to form teratoma-like structures. However, E21 kidney or liver tissue markedly enhanced the growth and function of E28 kidney, liver, and heart grafts. Moreover, similar growth enhancement was observed on coimplantation of E28 liver tissue with MEF or on infusion of MEF culture medium, indicating that this enhancement is likely mediated through soluble factors secreted by the fibroblasts. Our results suggest a novel approach for the enhancement of growth and differentiation of transplanted embryonic tissues by the use of soluble factors secreted by embryonic fibroblasts.

Down-regulated RPS3a/nbl expression during retinoid-induced differentiation of HL-60 cells: a close association with diminished susceptibility to actinomycin D-stimulated apoptosis.

PubMed

Russell, L; Naora, H; Naora, H

2000-04-01

The efficacy of anticancer agents significantly depends on the differential susceptibility of undifferentiated cancer cells and differentiated normal cells to undergo apoptosis. We previously found that enhanced expression of RPS3a/nbl, which apparently encodes a ribosomal protein, seems to prime cells for apoptosis, while suppressing such enhanced expression triggers cell death. The present study found that HL-60 cells induced to differentiate by all-trans retinoic acid did not undergo apoptosis following treatment with actinomycin D whereas undifferentiated HL-60 cells were highly apoptosis-susceptible, confirming earlier suggestions that differentiated cells have diminished apoptosis-susceptibility. Undifferentiated HL-60 cells highly expressed RPS3a/nbl whereas all-trans retinoic acid -induced differentiated cells exhibited markedly reduced levels, suggesting that apoptosis-resistance of differentiated cells could be due to low RPS3a/nbl expression. Down-regulation of enhanced RPS3a/nbl expression was also observed in cells induced to differentiate with the retinoid 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthalenyl)-1- propenyl]benzoic acid without any significant induction of cell death. While down-regulation of RPS3a/nbl expression during differentiation did not apparently induce apoptosis, RPS3a/nbl antisense oligomers triggered death of undifferentiated HL-60 cells, but not of retinoid-induced differentiated cells. It therefore seems that while down-regulation of enhanced RPS3a/nbl expression can induce apoptosis in undifferentiated cells, down-regulation of enhanced RPS3a/nbl expression during differentiation occurs independently of apoptosis, and could be regarded as reverting the primed condition to the unprimed (low RPS3a/nbl) state.

ICG-enhanced imaging of arthritis with an integrated Optical Imaging/X-ray System

PubMed Central

Meier, Reinhard; Krug, Christian; Golovko, Daniel; Boddington, Sophie; Piontek, Guido; Rudelius, Martina; Sutton, Elizabeth J.; Baur-Melnyk, Andrea; Jones, Ella F.; Daldrup-Link, Heike E.

2010-01-01

Background Optical Imaging (OI) is a promising technique that is quick, inexpensive and, in combination with Indocyanine Green (ICG), an FDA-approved fluorescent dye, could provide early detection of rheumatoid arthritis. Objective The purpose of this study was to evaluate a combined X-ray/OI imaging system for ICG-enhanced detection of arthritic joints in a rat model of antigen induced arthritis. Methods Arthritis of the knee and ankle joints was induced in six Harlan rats with peptidoglycan polysaccharide polymers (PGPS). Three rats served as non-treated controls. Optical imaging of the knee and ankle joints was done with an integrated OI/X-ray system before and up to 24h post intravenous injection (p.i.) of 10mg/kg ICG. The fluorescence signal intensities of arthritic and normal joints were compared for significant differences using generalized estimation equation models. Specimen of knee and ankle joints were further processed and evaluated by histology. Results ICG provided a significant increase in fluorescence signal of arthritic joints compared to baseline values immediately after administration (p<0.05). The fluorescence signal of arthritic joints was significantly higher compared to the non-arthritic control joints at 1 - 720 min p.i. (p<0.05). Fusion of ICG-enhanced OI and X-rays allowed for anatomical co-registration of the inflamed tissue with the associated joint. H&E stains confirmed marked synovial inflammation of arthritic joints and absence of inflammation in control joints. Conclusion ICG-enhanced OI is a clinically applicable tool for detection of arthritic tissue. Using relatively high doses of ICG, a long term fluorescence enhancement of arthritic joints can be achieved. This may facilitate simultaneous evaluations of multiple joints in a clinical setting. Fusion of ICG-OI scans with X-ray imaging increases anatomical resolution. PMID:20506388

s-SHIP expression identifies a subset of murine basal prostate cells as neonatal stem cells

PubMed Central

Brocqueville, Guillaume; Chmelar, Renee S.; Bauderlique-Le Roy, Hélène; Deruy, Emeric; Tian, Lu; Vessella, Robert L.; Greenberg, Norman M.; Bourette, Roland P.

2016-01-01

Isolation of prostate stem cells (PSCs) is crucial for understanding their biology during normal development and tumorigenesis. In this aim, we used a transgenic mouse model expressing GFP from the stem cell-specific s-SHIP promoter to mark putative stem cells during postnatal prostate development. Here we show that cells identified by GFP expression are present transiently during early prostate development and localize to the basal cell layer of the epithelium. These prostate GFP+ cells are a subpopulation of the Lin− CD24+ Sca-1+ CD49f+ cells and are capable of self-renewal together with enhanced growth potential in sphere-forming assay in vitro, a phenotype consistent with that of a PSC population. Transplantation assays of prostate GFP+ cells demonstrate reconstitution of prostate ducts containing both basal and luminal cells in renal grafts. Altogether, these results demonstrate that s-SHIP promoter expression is a new marker for neonatal basal prostate cells exhibiting stem cell properties that enables PSCs in situ identification and isolation via a single consistent parameter. Transcriptional profiling of these GFP+ neonatal stem cells showed an increased expression of several components of the Wnt signaling pathway. It also identified stem cell regulators with potential applications for further analyses of normal and cancer stem cells. PMID:27081082

Infuence of Averaging Method on the Evaluation of a Coastal Ocean Color Event on the U.S. Northeast Coast

NASA Technical Reports Server (NTRS)

Acker, James G.; Uz, Stephanie Schollaert; Shen, Suhung; Leptoukh, Gregory G.

2010-01-01

Application of appropriate spatial averaging techniques is crucial to correct evaluation of ocean color radiometric data, due to the common log-normal or mixed log-normal distribution of these data. Averaging method is particularly crucial for data acquired in coastal regions. The effect of averaging method was markedly demonstrated for a precipitation-driven event on the U.S. Northeast coast in October-November 2005, which resulted in export of high concentrations of riverine colored dissolved organic matter (CDOM) to New York and New Jersey coastal waters over a period of several days. Use of the arithmetic mean averaging method created an inaccurate representation of the magnitude of this event in SeaWiFS global mapped chl a data, causing it to be visualized as a very large chl a anomaly. The apparent chl a anomaly was enhanced by the known incomplete discrimination of CDOM and phytoplankton chlorophyll in SeaWiFS data; other data sources enable an improved characterization. Analysis using the geometric mean averaging method did not indicate this event to be statistically anomalous. Our results predicate the necessity of providing the geometric mean averaging method for ocean color radiometric data in the Goddard Earth Sciences DISC Interactive Online Visualization ANd aNalysis Infrastructure (Giovanni).

59-year-old female with breathlessness.

PubMed

Scatteia, Alessandra; De Garate, Estefania; Bucciarelli-Ducci, Chiara

2016-10-15

A 59-year-old female underwent an electrocardiogram (ECG) and echocardiographic screening. Her brother died at quite a young age of kidney failure. Resting ECG showed borderline voltage criteria for left ventricular hypertrophy (LVH), with marked widespread T-wave inversion. Echocardiogram was normal, but in consideration of exertional breathlessness and abnormal baseline ECG, she underwent a coronary angiogram, which showed unobstructed coronaries. She was then referred to have a cardiac MR (CMR) for further characterisation. CMR images were acquired with a 1.5 T scanner and the imaging protocol included Steady-State Free Precession (SSFP) cine images (Figure 1A) as well as late gadolinium enhancement (LGE) images in the long-axis and short-axis planes covering the whole left ventricle (Figure 1B). In addition, native and postcontrast T1 mapping (Modified Look-Locker (MOLLI)) images were acquired for further tissue characterisation (Figure 1C and D, respectively). What is the most likely diagnosis based on CMR findings? Anderson-Fabry's disease (AFD)Cardiac amyloidosisGenotype (+), phenotype (-) hypertrophic cardiomyopathy (HCM)Myocardial iron overloadNormal heart. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Specific Calpain Inhibition by Calpastatin Prevents Tauopathy and Neurodegeneration and Restores Normal Lifespan in Tau P301L Mice

PubMed Central

McBrayer, Mary Kate; Campbell, Jabbar; Kumar, Asok; Hashim, Audrey; Sershen, Henry; Stavrides, Philip H.; Ohno, Masuo; Hutton, Michael; Nixon, Ralph A.

2014-01-01

Tau pathogenicity in Alzheimer's disease and other tauopathies is thought to involve the generation of hyperphosphorylated, truncated, and oligomeric tau species with enhanced neurotoxicity, although the generative mechanisms and the implications for disease therapy are not well understood. Here, we report a striking rescue from mutant tau toxicity in the JNPL3 mouse model of tauopathy. We show that pathological activation of calpains gives rise to a range of potentially toxic forms of tau, directly, and by activating cdk5. Calpain overactivation in brains of these mice is accelerated as a result of the marked depletion of the endogenous calpain inhibitor, calpastatin. When levels of this inhibitor are restored in neurons of JNPL3 mice by overexpressing calpastatin, tauopathy is prevented, including calpain-mediated breakdown of cytoskeletal proteins, cdk5 activation, tau hyperphosphorylation, formation of potentially neurotoxic tau fragments by either calpain or caspase-3, and tau oligomerization. Calpastatin overexpression also prevents loss of motor axons, delays disease onset, and extends survival of JNPL3 mice by 3 months to within the range of normal lifespan. Our findings support the therapeutic promise of highly specific calpain inhibition in the treatment of tauopathies and other neurodegenerative states. PMID:25009256

Few CT Scan Abnormalities Found Even in Neurologically Impaired Learning Disabled Children.

ERIC Educational Resources Information Center

Denckla, Martha Bridge; And Others

1985-01-01

Most of 32 learning disabled children (seven to 14 years old) with neurological lateralization characteristics marked by right and left hemispheres had a normal CT (computerized tomography) scan. (CL)

Deletion of Mecom in mouse results in early-onset spinal deformity and osteopenia.

PubMed

Juneja, Subhash C; Vonica, Alin; Zeiss, Caroline; Lezon-Geyda, Kimberly; Yatsula, Bogdan; Sell, David R; Monnier, Vincent M; Lin, Sharon; Ardito, Thomas; Eyre, David; Reynolds, David; Yao, Zhenqiang; Awad, Hani A; Yu, Hongbo; Wilson, Michael; Honnons, Sylvie; Boyce, Brendan F; Xing, Lianping; Zhang, Yi; Perkins, Archibald S

2014-03-01

Recent studies have indicated a role for a MECOM allele in susceptibility to osteoporotic fractures in humans. We have generated a mutation in Mecom in mouse (termed ME(m1)) via lacZ knock-in into the upstream transcription start site for the gene, resulting in disruption of Mds1 and Mds1-Evi1 transcripts, but not of Evi1 transcripts. We demonstrate that ME(m1/m1) mice have severe kyphoscoliosis that is reminiscent of human congenital or primary kyphoscoliosis. ME(m1/m1) mice appear normal at birth, but by 2weeks, they exhibit a slight lumbar lordosis and narrowed intervertebral space. This progresses to severe lordosis with disc collapse and synostosis, together with kyphoscoliosis. Bone formation and strength testing show that ME(m1/m1) mice have normal bone formation and composition but are osteopenic. While endochondral bone development is normal, it is markedly dysplastic in its organization. Electron micrographs of the 1week postnatal intervertebral discs reveals marked disarray of collagen fibers, consistent with an inherent weakness in the non-osseous connective tissue associated with the spine. These findings indicate that lack of ME leads to a complex defect in both osseous and non-osseous musculoskeletal tissues, including a marked vertebral osteopenia, degeneration of the IVD, and disarray of connective tissues, which is likely due to an inherent inability to establish and/or maintain components of these tissues. Copyright © 2013 Elsevier Inc. All rights reserved.

Methods and computer executable instructions for marking a downhole elongate line and detecting same

DOEpatents

Watkins, Arthur D.

2003-05-13

Methods and computer executable instructions are provided for making an elongate line (22) with a plurality of marks (30) and detecting those marks (30) to determine a distance of the elongate line (22) in a downhole or a physical integrity thereof. In a preferred embodiment, each mark comprises a plurality of particles (44) having a substantially permanent magnetizing capability adhered to an exterior surface of the elongate line (22) at preselected intervals with an epoxy paint. The particles (44) are arranged at each interval as a plurality of bands (40). Thereafter, the particles are oriented into a magnetic signature for that interval by magnetizing the particles to create a magnetic field substantially normal to the exterior surface. This facilitates detection by a Hall effect probe. The magnetic signatures are stored in a computing configuration and, once a mark is detected, a correlation is made to a unique position on the elongate line by comparison with the stored magnetic signatures. Preferred particles include samarium-cobalt and neodymium-iron-boride.

Pilot of the Modern Army Record-Keeping System (MARKS) at 5th Battalion, 73rd Armored Regiment, 194th Armored Brigade, Fort Knox, Kentucky

DTIC Science & Technology

1984-08-01

statements. G. Monthly bank account reconciliations. h. Statements of operations and net worth. i. Reports of audit . j. Cash property and recon- ciliation...that a formal audit is unnecessary, the installation commander will insure that the records are destroyed on completion of the examination or...32 Clothing and Tex- (not normally used in 5/73) tile Materiel 34 Standardizaion (not normally used in 5/73) 36 Audit (not normally used in 5/73) 37

Peer Teaching to Foster Learning in Physiology.

PubMed

Srivastava, Tripti K; Waghmare, Lalitbhushan S; Mishra, Ved Prakash; Rawekar, Alka T; Quazi, Nazli; Jagzape, Arunita T

2015-08-01

Peer teaching is an effective tool to promote learning and retention of knowledge. By preparing to teach, students are encouraged to construct their own learning program, so that they can explain effectively to fellow learners. Peer teaching is introduced in present study to foster learning and pedagogical skills amongst first year medical under-graduates in physiology with a Hypothesis that teaching is linked to learning on part of the teacher. Non-randomized, Interventional study, with mixed methods design. Cases experienced peer teaching whereas controls underwent tutorials for four consecutive classes. Quantitative Evaluation was done through pre/post test score analysis for Class average normalized gain and tests of significance, difference in average score in surprise class test after one month and percentage of responses in closed ended items of feedback questionnaire. Qualitative Evaluation was done through categorization of open ended items and coding of reflective statements. The average pre and post test score was statistically significant within cases (p = 0.01) and controls (p = 0.023). The average post test scores was more for cases though not statistically significant. The class average normalized gain (g) for Tutorials was 49% and for peer teaching 53%. Surprise test had average scoring of 36 marks (out of 50) for controls and 41 marks for cases. Analysed section wise, the average score was better for Long answer question (LAQ) in cases. Section wise analysis suggested that through peer teaching, retention was better for descriptive answers as LAQ has better average score in cases. Feedback responses were predominantly positive for efficacy of peer teaching as a learning method. The reflective statements were sorted into reflection in action, reflection on action, claiming evidence, describing experience, and recognizing discrepancies. Teaching can stimulate further learning as it involves interplay of three processes: metacognitive awareness; deliberate practice, and self-explanation. Coupled with immediate feedback and reflective exercises, learning can be measurably enhanced along with improved teaching skills.

Peer Teaching to Foster Learning in Physiology

PubMed Central

Srivastava, Tripti K; Waghmare, Lalitbhushan S.; Mishra, Ved Prakash; Rawekar, Alka T; Quazi, Nazli; Jagzape, Arunita T

2015-01-01

Introduction Peer teaching is an effective tool to promote learning and retention of knowledge. By preparing to teach, students are encouraged to construct their own learning program, so that they can explain effectively to fellow learners. Peer teaching is introduced in present study to foster learning and pedagogical skills amongst first year medical under-graduates in physiology with a Hypothesis that teaching is linked to learning on part of the teacher. Materials and Methods Non-randomized, Interventional study, with mixed methods design. Cases experienced peer teaching whereas controls underwent tutorials for four consecutive classes. Quantitative Evaluation was done through pre/post test score analysis for Class average normalized gain and tests of significance, difference in average score in surprise class test after one month and percentage of responses in closed ended items of feedback questionnaire. Qualitative Evaluation was done through categorization of open ended items and coding of reflective statements. Results The average pre and post test score was statistically significant within cases (p = 0.01) and controls (p = 0.023). The average post test scores was more for cases though not statistically significant. The class average normalized gain (g) for Tutorials was 49% and for peer teaching 53%. Surprise test had average scoring of 36 marks (out of 50) for controls and 41 marks for cases. Analysed section wise, the average score was better for Long answer question (LAQ) in cases. Section wise analysis suggested that through peer teaching, retention was better for descriptive answers as LAQ has better average score in cases. Feedback responses were predominantly positive for efficacy of peer teaching as a learning method. The reflective statements were sorted into reflection in action, reflection on action, claiming evidence, describing experience, and recognizing discrepancies. Conclusion Teaching can stimulate further learning as it involves interplay of three processes: metacognitive awareness; deliberate practice, and self-explanation. Coupled with immediate feedback and reflective exercises, learning can be measurably enhanced along with improved teaching skills. PMID:26435969

Involvement of the P2X7 purinergic receptor in colonic motor dysfunction associated with bowel inflammation in rats.

PubMed

Antonioli, Luca; Giron, Maria Cecilia; Colucci, Rocchina; Pellegrini, Carolina; Sacco, Deborah; Caputi, Valentina; Orso, Genny; Tuccori, Marco; Scarpignato, Carmelo; Blandizzi, Corrado; Fornai, Matteo

2014-01-01

Recent evidence indicates an involvement of P2X7 purinergic receptor (P2X7R) in the fine tuning of immune functions, as well as in driving enteric neuron apoptosis under intestinal inflammation. However, the participation of this receptor in the regulation of enteric neuromuscular functions remains undetermined. This study was aimed at investigating the role of P2X7Rs in the control of colonic motility in experimental colitis. Colitis was induced in rats by 2,4-dinitrobenzenesulfonic acid. P2X7R distribution was examined by immunofluorescence analysis. The effects of A804598 (selective P2X7R antagonist) and BzATP (P2X7R agonist) were tested on contractions of longitudinal smooth muscle evoked by electrical stimulation or by carbachol in the presence of tetrodotoxin. P2X7Rs were predominantly located in myenteric neurons, but, in the presence of colitis, their expression increased in the neuromuscular layer. In normal preparations, A804598 elicited a negligible increase in electrically induced contractions, while a significant enhancement was recorded in inflamed tissues. In the presence of Nω-propyl-L-arginine (NPA, neuronal nitric oxide synthase inhibitor) the A804598 effects were lost. P2X7R stimulation with BzATP did not significantly affect electrical-induced contractions in normal colon, while a marked reduction was recorded under inflammation. The inhibitory effect of BzATP was antagonized by A804598, and it was also markedly blunted by NPA. Both P2X7R ligands did not affect carbachol-induced contractions. The purinergic system contributes to functional neuromuscular changes associated with bowel inflammation via P2X7Rs, which modulate the activity of excitatory cholinergic nerves through a facilitatory control on inhibitory nitrergic pathways.

Cardiopulmonary protective effects of the selective FXR agonist obeticholic acid in the rat model of monocrotaline-induced pulmonary hypertension.

PubMed

Vignozzi, Linda; Morelli, Annamaria; Cellai, Ilaria; Filippi, Sandra; Comeglio, Paolo; Sarchielli, Erica; Maneschi, Elena; Vannelli, Gabriella Barbara; Adorini, Luciano; Maggi, Mario

2017-01-01

Farnesoid X receptor (FXR) activation by obeticholic acid (OCA) has been demonstrated to inhibit inflammation and fibrosis development and even induce fibrosis regression in liver, kidney and intestine in multiple disease models. OCA also inhibits liver fibrosis in nonalcoholic steatohepatitis patients. FXR activation has also been demonstrated to suppress the inflammatory response and to promote lung repair after lung injury. This study investigated the effects of OCA treatment (3, 10 or 30mg/kg, daily for 5days a week, for 7 and/or 28 days) on inflammation, tissue remodeling and fibrosis in the monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) rat model. Treatment with OCA attenuated MCT-induced increased pulmonary arterial wall thickness and right ventricular hypertrophy, by i) blunting pathogenic inflammatory mechanisms (downregulation of interleukin 6, IL-6, and monocyte chemoattractant protein-1, MCP-1) and ii) enhancing protective mechanisms counteracting fibrosis and endothelial/mesenchymal transition. MCT-injected rats also showed a marked decrease of pulmonary artery responsiveness to both endothelium-dependent and independent relaxant stimuli, such as acetylcholine and a nitric oxide donor, sodium nitroprusside. Administration of OCA (30mg/kg) normalized this decreased responsiveness. Accordingly, OCA treatment induced profound beneficial effects on lung histology. In particular, both OCA doses markedly reduced the MCT-induced medial wall thickness increase in small pulmonary arteries. To evaluate the objective functional improvement by OCA treatment of MCT-induced PAH, we performed a treadmill test and measured duration of exercise. MCT significantly reduced, and OCA normalized treadmill endurance. Results with OCA were similar, or even superior, to those obtained with tadalafil, a well-established treatment of PAH. In conclusion, OCA treatment demonstrates cardiopulmonary protective effects, modulating lung vascular remodeling, reducing right ventricular hypertrophy and significantly improving exercise capacity. Thus, OCA can restore the balance between relaxant and contractile pathways in the lung, promoting cardiopulmonary protective actions. Copyright © 2016 Elsevier Ltd. All rights reserved.

MR imaging of intracranial hemangiopericytomas.

PubMed

Mama, N; Ben Abdallah, A; Hasni, I; Kadri, K; Arifa, N; Ladib, M; Tlili-Graiess, K

2014-12-01

To describe the MR features of primary intracranial hemangiopericytomas (HPCs) on conventional imaging, diffusion and MR spectroscopy and aim to determinate distinguishing features from meningiomas. From 2006 to 2012, seven patients with pathologically confirmed primary intracranial HPCs were included. The clinical data, conventional MR findings (n=7), DWI features (n=7) and MR spectroscopy (n=5) were retrospectively analyzed. ADC values of the HPCs (n=7) were measured on ADC map and were compared with that of contralateral normal white matter. Of the seven HPCs, four were anaplastic HPCs (WHO grade III) and three were HPCs (WHO grade II). MR pattern consisted in lobulated or irregular margin tumors in all cases with cross-leaf growth on both side of the falx in two cases. The lesions showed mainly iso signal (n=4) on T1 WI and heterogeneous high signal (n=5) on T2 WI. Heterogenity was mainly related to intra tumoral hemorrhage (n=4), and proeminent intratumoral flow voids (n=3). Marked heterogeneous enhancement (n=5) with dural tail (n=4) was noted. All tumours showed significant peritumoral edema. ADC values of the tumor tissue component range between 0.638 and 1.50×10(-3)mm/s(2) (average = 1,02). Three grade II HPCs showed higher values compared to normal parenchyma ADC (range between 0.772 and 0.930×10(-3)mm/s(2) with average of 0.830), whereas grade III HPCs showed either equal (three cases) or decreased ADC values (one case). MRS showed in all cases markedly increased Cho with lip/lac peak, decreased Cr and almost absent NAA. High mI peak with large glutamine/glutamate were noted in the three grade II HPCs. Conventional MR pattern when combined with DWI and MRS findings are highly suggestive of HPC and appear valuable data to differentiate HPCs from meningiomas. Copyright © 2014. Published by Elsevier Masson SAS.

Development and Application of Advanced Ophthalmic Imaging Technology to Enhance Military Ocular Health Capabilities

DTIC Science & Technology

2008-04-01

V. X. D. Yang, M. L. Gordon, A. Mok, Y. Zhao, Z. Chen, R. Cobbold , B. Wilson, and I. Vitkin, " Improve.d pha<e. re;olve.d optical Doppler tomography... marked according to visualmea~urement (b), rutd the result of the moving circular window filtering. In this case, the location of the mininttun...botmdaries are marked on the OCT image; (g). The ODT image for the same OCT scan; (h). Magnified \\<iew of the region marked in (_ll,). where. the

Differential Regulation of Protein- and Polysaccharide-Specific Ig Isotype Production In Vivo in Response to Intact Streptococcus pneumoniae

DTIC Science & Technology

2006-01-01

IL-4-/- mice. A marked enhancement in the induction of pro-inflammatory cytokines was observed in the absence of IL- 10, relative to controls. IgG...that it was phenol-extractable. Immunization of wild-type mice with phenol-extracted PPS14 also resulted in a marked reduction in the IgG, although not...Thus, CBA/N (xid) mice [124], which have a loss-of-function point mutation in the Btk gene [125, 126] exhibit a marked reduction in peritoneal B-1a

Limiting prolonged inflammation during proliferation and remodeling phases of wound healing in streptozotocin-induced diabetic rats supplemented with camel undenatured whey protein.

PubMed

Ebaid, Hossam; Ahmed, Osama M; Mahmoud, Ayman M; Ahmed, Rasha R

2013-07-25

Impaired diabetic wound healing occurs as a consequence of excessive reactive oxygen species (ROS) and inflammatory cytokine production. We previously found that whey protein (WP) was able to normally regulate the ROS and inflammatory cytokines during the inflammatory phase (first day) in streptozotocin (STZ)-diabetic wound healing. This study was designed to assess the effect of WP on metabolic status, the inflammation and anti-inflammation response, oxidative stress and the antioxidant defense system during different phases of the wound healing process in diabetic rats. WP at a dosage of 100 mg/kg of body weight, dissolved in 1% CMC, was orally administered daily to wounded normal (non-diabetic) and STZ-induced diabetic rats for 8 days starting from the 1st day after wounding. The data revealed that WP enhanced wound closure and was associated with an increase in serum insulin levels in diabetic rats and an alleviation of hyperglycemic and hyperlipidemic states in diabetic animals. The increase in insulin levels as a result of WP administration is associated with a marked multiplication of β-cells in the core of islets of Langerhans. WP induced a reduction in serum TNF-α, IL-1β and IL-6 levels and an increase in IL-10 levels, especially on the 4th day after wounding and treatment. WP also suppressed hepatic lipid peroxidation and stimulated the antioxidant defense system by increasing the level of glutathione and the activity of glutathione-S-transferase, glutathione peroxidase and superoxide dismutase (SOD) in wounded diabetic rats. WP was observed to enhance wound closure by improving the diabetic condition, limiting prolonged inflammation, suppressing oxidative stress and elevating the antioxidant defense system in diabetic rats.

The in vivo effect of fibrinogen and factor XIII on clot formation and fibrinolysis in Glanzmann's thrombasthenia.

PubMed

Shenkman, Boris; Livnat, Tami; Misgav, Mudi; Budnik, Ivan; Einav, Yulia; Martinowitz, Uriel

2012-01-01

Glanzmann's thrombasthenia (GT) is characterized by increased bleeding risk. The treatment options in GT are limited. The aim of this study was to test the effect of GT blood supplementation with fibrinogen and factor XIII on thrombin generation, blood clotting, and fibrinolysis. Whole blood samples of GT patients and normal donors treated with eptifibatide (GT model) were subjected to clotting by CaCl(2) and tissue factor. Thrombin generation was measured in platelet-rich plasma. Clot formation and tPA-induced fibrinolysis were evaluated in whole blood by rotation thromboelastometry (ROTEM). Blood was supplemented with fibrinogen (3 g/L) and/or FXIII (2 IU/mL). Thrombin generation analysis of blood derived from GT model and GT patients revealed decreased endogenous thrombin potential and peak height and extended lag time compared to control. However, this method was not sensitive to blood spiking with fibrinogen and FXIII. ROTEM revealed lower maximum clot firmness (MCF) and area under curve (AUC) in the blood of GT model and GT patients. In the absence of exogenous tPA, blood spiking with fibrinogen markedly enhanced clot quality while FXIII had no effect. Combination of fibrinogen and FXIII did not add to the effect of fibrinogen. In contrast, by the addition of tPA, both fibrinogen and FXIII separately and, to more extent, in combination enhanced clot quality as well as resistance against tPA-induced fibrinolysis (increasing MCF, AUC, and lysis onset time). In conclusion, fibrinogen and FXIII exerted stimulation of blood clotting and inhibition of fibrinolysis. Treating normal blood with eptifibatide mimics the changes of coagulopathy in GT blood.

Spectroscopic characterization of biological agents using FTIR, normal Raman and surface-enhanced Raman spectroscopies

NASA Astrophysics Data System (ADS)

Luna-Pineda, Tatiana; Soto-Feliciano, Kristina; De La Cruz-Montoya, Edwin; Pacheco Londoño, Leonardo C.; Ríos-Velázquez, Carlos; Hernández-Rivera, Samuel P.

2007-04-01

FTIR, Raman spectroscopy and Surface Enhanced Raman Scattering (SERS) requires a minimum of sample allows fast identification of microorganisms. The use of this technique for characterizing the spectroscopic signatures of these agents and their stimulants has recently gained considerable attention due to the fact that these techniques can be easily adapted for standoff detection from considerable distances. The techniques also show high sensitivity and selectivity and offer near real time detection duty cycles. This research focuses in laying the grounds for the spectroscopic differentiation of Staphylococcus spp., Pseudomonas spp., Bacillus spp., Salmonella spp., Enterobacter aerogenes, Proteus mirabilis, Klebsiella pneumoniae, and E. coli, together with identification of their subspecies. In order to achieve the proponed objective, protocols to handle, cultivate and analyze the strains have been developed. Spectroscopic similarities and marked differences have been found for Spontaneous or Normal Raman spectra and for SERS using silver nanoparticles have been found. The use of principal component analysis (PCA), discriminate factor analysis (DFA) and a cluster analysis were used to evaluate the efficacy of identifying potential threat bacterial from their spectra collected on single bacteria. The DFA from the bacteria Raman spectra show a little discrimination between the diverse bacterial species however the results obtained from the SERS demonstrate to be high discrimination technique. The spectroscopic study will be extended to examine the spores produced by selected strains since these are more prone to be used as Biological Warfare Agents due to their increased mobility and possibility of airborne transport. Micro infrared spectroscopy as well as fiber coupled FTIR will also be used as possible sensors of target compounds.

Limiting prolonged inflammation during proliferation and remodeling phases of wound healing in streptozotocin-induced diabetic rats supplemented with camel undenatured whey protein

PubMed Central

2013-01-01

Background Impaired diabetic wound healing occurs as a consequence of excessive reactive oxygen species (ROS) and inflammatory cytokine production. We previously found that whey protein (WP) was able to normally regulate the ROS and inflammatory cytokines during the inflammatory phase (first day) in streptozotocin (STZ)-diabetic wound healing. This study was designed to assess the effect of WP on metabolic status, the inflammation and anti-inflammation response, oxidative stress and the antioxidant defense system during different phases of the wound healing process in diabetic rats. WP at a dosage of 100 mg/kg of body weight, dissolved in 1% CMC, was orally administered daily to wounded normal (non-diabetic) and STZ-induced diabetic rats for 8 days starting from the 1st day after wounding. Results The data revealed that WP enhanced wound closure and was associated with an increase in serum insulin levels in diabetic rats and an alleviation of hyperglycemic and hyperlipidemic states in diabetic animals. The increase in insulin levels as a result of WP administration is associated with a marked multiplication of β-cells in the core of islets of Langerhans. WP induced a reduction in serum TNF-α, IL-1β and IL-6 levels and an increase in IL-10 levels, especially on the 4th day after wounding and treatment. WP also suppressed hepatic lipid peroxidation and stimulated the antioxidant defense system by increasing the level of glutathione and the activity of glutathione-S-transferase, glutathione peroxidase and superoxide dismutase (SOD) in wounded diabetic rats. Conclusions WP was observed to enhance wound closure by improving the diabetic condition, limiting prolonged inflammation, suppressing oxidative stress and elevating the antioxidant defense system in diabetic rats. PMID:23883360

Enhancer of zeste homolog 2 blockade by RNA interference is implicated with inhibited proliferation, invasion and promoted apoptosis in endometrial carcinoma.

PubMed

Wang, Juan; Ai, Zhihong; Chen, Jing; Teng, Yincheng; Zhu, Jieping

2018-06-01

Endometrial carcinoma is the most common gynecological malignancy of the female genital tract worldwide (2012). Enhancer of zeste homolog 2 (EZH2), a critical component of the polycomb repressive complex 2, has been found to be associated with multiple biological processes and is overexpressed in multiple types of cancer. Previous studies have demonstrated that EZH2 is associated with endometrial carcinoma. The present study investigated the expression and biology function of EZH2 in endometrial cancer (EC). It was found that EZH2 levels were markedly increased in endometrial cancer tissues compared with that in adjacent normal tissues. EZH2 was significantly overexpressed in 3 separate endometrial cancer cell lines (Ishikawa, RL95-2 and HEC1-A) when compared with the normal endometrial cell line ESC. Additionally, small interfering RNA was used to investigate the role of EZH2 in endometrial carcinoma cell proliferation, and the results showed that EZH2 knockdown suppressed the proliferation of endometrial carcinoma cells in vitro . Furthermore, EZH2 knockdown induced apoptosis of human EC cells by promoting the expression of pro-apoptosis protein caspase 3, caspase 9, BCL2 associated X and decreasing the expression of anti-apoptosis protein Bcl-2. Finally, the present study demonstrated that EZH2 knockdown suppressed the invasion of EC cells through downregulation of the epithelial-mesenchymal transition. Collectively, these data demonstrate that EZH2 is frequently overexpressed in EC cells and its overexpression is associated with promoting the proliferation and invasion and decreasing the apoptosis of EC cells, suggesting that EZH2 may provide potential therapeutic targets for treatment of endometrial carcinoma.

A Trust-Based Adaptive Probability Marking and Storage Traceback Scheme for WSNs

PubMed Central

Liu, Anfeng; Liu, Xiao; Long, Jun

2016-01-01

Security is a pivotal issue for wireless sensor networks (WSNs), which are emerging as a promising platform that enables a wide range of military, scientific, industrial and commercial applications. Traceback, a key cyber-forensics technology, can play an important role in tracing and locating a malicious source to guarantee cybersecurity. In this work a trust-based adaptive probability marking and storage (TAPMS) traceback scheme is proposed to enhance security for WSNs. In a TAPMS scheme, the marking probability is adaptively adjusted according to the security requirements of the network and can substantially reduce the number of marking tuples and improve network lifetime. More importantly, a high trust node is selected to store marking tuples, which can avoid the problem of marking information being lost. Experimental results show that the total number of marking tuples can be reduced in a TAPMS scheme, thus improving network lifetime. At the same time, since the marking tuples are stored in high trust nodes, storage reliability can be guaranteed, and the traceback time can be reduced by more than 80%. PMID:27043566

Canonical Wnt Signaling as a Specific Mark of Normal and Tumorigenic Mammary Stem Cells

DTIC Science & Technology

2011-02-01

aggressive mammary tumors. 15. SUBJECT TERMS Breast cancer stem cells, Wnt signaling, canonical Wnt signaling, B-catenin, normal stem cells, adult stem...Wnt pathway is associated with abnormal mouse mammary development, tumorigenesis, and human breast cancer. In addition, increasing evidence suggests...activation occurs in human breast cancer and is required for proliferation of various other stem cell compartments, addressing how Wnt signaling promotes

Coordinating Self-Assembly of Copper Perylenetetracarboxylate Nanorods: Selectively Lighting up Normal Cells around Cancerous Ones for Better Cancer Diagnosis.

PubMed

Wang, Lizhi; Gao, Xuedong; Wei, Ying; Liu, Kaerdun; Huang, Jianbin; Wang, Jide; Yan, Yun

2018-05-30

Specific imaging of cancer cells has been well-accepted in cancer diagnosis although it cannot precisely mark the boundary between the normal and cancerous cells and report their mutual influence. We report a nanorod fluorescent probe of copper perylenetetracarbonate (PTC-Cu) that can specifically light up normal cells. In combination with cancer cell imaging, the cocultured normal and cancer cells can be lit up with different colors, offering a clear contrast between the normal and cancer cells when they coexist. Because cancerous cells are only 20-30% in cancer area, this provides a possibility to visibly detect the mutual influence between the cancer and normal cells during therapy. We expect this method is beneficial to better cancer diagnosis and therapy.

Modeling Enhanced Storage of Groundwater Contaminants due to the Presence of Cracks in Low Permeability Zones Underlying Contaminant Source Areas

DTIC Science & Technology

2011-03-01

Approved: //signed// 11 Mar 2011 __________________________________ _________ Mark N. Goltz , Ph.D. (Chairman) Date...Acknowledgments I appreciate the opportunity my thesis adviser, Dr. Mark N. Goltz , gave me by allowing me to work with him on this thesis topic and...3.15 is used ( Goltz and Roberts, 1988). R D B R

Global analysis of H3K27me3 as an epigenetic marker in prostate cancer progression.

PubMed

Ngollo, Marjolaine; Lebert, Andre; Daures, Marine; Judes, Gaelle; Rifai, Khaldoun; Dubois, Lucas; Kemeny, Jean-Louis; Penault-Llorca, Frederique; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

2017-04-12

H3K27me3 histone marks shape the inhibition of gene transcription. In prostate cancer, the deregulation of H3K27me3 marks might play a role in prostate tumor progression. We investigated genome-wide H3K27me3 histone methylation profile using chromatin immunoprecipitation (ChIP) and 2X400K promoter microarrays to identify differentially-enriched regions in biopsy samples from prostate cancer patients. H3K27me3 marks were assessed in 34 prostate tumors: 11 with Gleason score > 7 (GS > 7), 10 with Gleason score ≤ 7 (GS ≤ 7), and 13 morphologically normal prostate samples. Here, H3K27me3 profiling identified an average of 386 enriched-genes on promoter regions in healthy control group versus 545 genes in GS ≤ 7 and 748 genes in GS > 7 group. We then ran a factorial discriminant analysis (FDA) and compared the enriched genes in prostate-tumor biopsies and normal biopsies using ANOVA to identify significantly differentially-enriched genes. The analysis identified ALG5, EXOSC8, CBX1, GRID2, GRIN3B, ING3, MYO1D, NPHP3-AS1, MSH6, FBXO11, SND1, SPATS2, TENM4 and TRA2A genes. These genes are possibly associated with prostate cancer. Notably, the H3K27me3 histone mark emerged as a novel regulatory mechanism in poor-prognosis prostate cancer. Our findings point to epigenetic mark H3K27me3 as an important event in prostate carcinogenesis and progression. The results reported here provide new molecular insights into the pathogenesis of prostate cancer.

Non-destructive analysis of the conformational changes in human lens lipid and protein structures of the immature cataracts associated with glaucoma

NASA Astrophysics Data System (ADS)

Lin, Shan-Yang; Li, Mei-Jane; Liang, Run-Chu; Lee, Shui-Mei

1998-09-01

Previous study has supposed a possible mechanism of exacerbating cataract formation in cataractous human lens capsules induced by hypertension or glaucoma. To clarify the glaucoma-induced cataract formation of the eyes lens, changes in the human lens lipid and protein structures of immature cataractous patients with or without glaucoma were investigated. Two normal lenses, ten immature cataractous lenses without any complication and four immature cataractous lenses with glaucoma were used after surgical operation. Each de-capsulated human lens sample was sliced with a number 15 surgical blade. The intact nuclear lens regions were used for non-destructive analysis. The lens lipid and protein structures, as well as compositions of these lens samples, were determined using a Fourier transform infrared (FTIR) microspectroscopy with second-derivative, de-convolution and curve-fitting methods. The results indicate that the IR spectrum of glaucomatous lenses appeared as a shoulder only at 2853 cm -1, thus the composition of the symmetric CH 2 stretching band at 2853 (2852) cm -1 decreased more significantly in glaucomatous lens to only one half of that in normal and immature cataractous lenses. The composition of the asymmetric CH 3 stretching band at 2965 cm -1 for normal lens decreases markedly from 32 to 20% for immature cataractous lenses with or without glaucoma. The compositional ratio of component at 2965 cm -1 to component at 2928 (2930) cm -1 for normal lenses was about 0.702, and that ratio for cataractous lenses without glaucoma was 0.382 but for glaucomatous lenses was 0.377. The maximum peak position of amide I band for IR spectra of the normal lens, immature cataractous lenses without complications or glaucomatous lenses appeared respectively at 1632, 1630 or 1622 cm -1, assigned to β sheet structure. A marked difference in peak intensity of amide I band for the normal lenses and immature cataractous human lenses with or without glaucoma was observed. The peak intensity ratio of amide I /amide II (1632/1545 cm -1) for normal lenses was in the range of 2.20-2.33, whereas in the spectra of immature cataractous lenses without glaucoma this ratio (1630/1545 cm -1) was 1.28-1.41 but was 1.04-1.13 for glaucomatous lens in the intensity ratio of 1622/1545 cm -1. The intensity of the glycogen bands in the wavenumber region 1135-1076 and 1069-1032 cm -1 was found to increase for the immature cataractous lenses with or without glaucoma, as compared with the normal ones. The peaks ranging from 1633 to 1610 cm -1 assigned to β-sheet structure also exhibited a pronounced compositional difference, particularly in glaucomatous lenses. The human lens lipid and protein secondary structures were more affected by glaucoma. Higher protein side chains and reduced lipid content contributed predominantly to the CH stretching vibrations of normal lens structure, whereas high lipid content and less protein side chains dominated the CH stretching vibrations of cataractous lenses with or without glaucoma. Decrease α-helix and random coil structures but enhanced β-sheet structure in the immature cataractous human lens induced by glaucoma might result from the formation of intermolecular hydrogen-bonding insoluble protein aggregates that modify the secondary structure of protein in lenses.

Peripheral zone lesions of intermediary risk in multiparametric prostate MRI: Frequency and validation of the PI-RADSv2 risk stratification algorithm based on focal contrast enhancement.

PubMed

Benndorf, Matthias; Waibel, Lorenz; Krönig, Malte; Jilg, Cordula Annette; Langer, Mathias; Krauss, Tobias

2018-02-01

To validate the risk stratification algorithm of the Prostate Imaging Reporting and Data System (PI-RADSv2) for intermediary risk lesions (PI-RADSv2 category 3) in the peripheral zone based on focal contrast enhancement and to compare cancer rates in category 3, upgraded category 4 and category 4 based on markedly low ADC value. We retrospectively analyze 172 consecutive patients undergoing prostate MRI with 315 histopathologically verified lesions. We select all lesions either assigned category 3 or category 4 in the peripheral zone for further analysis. We compare cancer rates with the two-sided chi-squared test. To determine inter-observer agreement about contrast enhancement two blinded radiologists evaluate the subset of category 3 lesions based on the diffusion weighted sequence. The frequency of peripheral PI-RADS 3, upgraded PI-RADS 4 and PI-RADS 4 lesions based on markedly low ADC value is 10.8%, 10.8% and 20.3%, respectively. Cancer rates (significant cancer only) in these subgroups are 8.8% (3/34), 23.5% (8/34) and 40.6% (26/64), P < 0.01. Inter-observer agreement is moderate for evaluation of contrast enhancement with kappa values between 0.46 and 0.5. We demonstrate a trend of increasing cancer rate from PI-RADSv2 category 3 to upgraded category 4 to category 4 based on markedly low ADC value. Peripheral lesions of intermediary risk in the diffusion weighted sequence account for 21.6% of all prostate lesions encountered. Since it is likely that patient management recommendations will be linked to assessment categories in future versions of PI-RADS, cancer rates in upgraded category 4 and category 4 based on markedly low ADC values should be in a similar range. We conclude that in future studies of PI-RADSv2 upgraded category 4 and category 4 based on markedly low ADC value should be reported separately to generate a database for meta-analysis of cancer rates. Copyright © 2017 Elsevier B.V. All rights reserved.

Biphasic positive effect of formononetin on metabolic activity of human normal and osteoarthritic subchondral osteoblasts.

PubMed

Huh, Jeong-Eun; Seo, Dong-Min; Baek, Yong-Hyeon; Choi, Do-Young; Park, Dong-Suk; Lee, Jae-Dong

2010-04-01

Osteoarthritis is a multifactorial disease characterized by loss of articular cartilage and subchondral plate thickening. Therefore, biochemical analysis of the underlying bone tissue has provided important information for treatment of osteoarthritis. In this study, we determined the potential role of formononetin, a phytoestrogen isolated from Astragalus membranaceus to alter the expression of metabolic markers and cytokine production of human normal osteoblasts (Obs) and osteoarthritis subchondral osteoblasts (OA Obs). Human OA Obs and normal Obs were cultured for 3days, 7days or 14days in the present medium only or were treated with various doses of formononetin. Cells were analyzed for viability by WST-8 assay, alkaline phosphatase (ALP) activity, osteogenic markers (osteocalcin (OCN) and type I collagen (Col I)) and cytokines (interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), bone morphogenic protein-2 (BMP-2)). The level of IL-6, VEGF, BMP-2, OCN and Col I was increased in OA Obs compared with normal Obs. Formononetin dose-dependently decreased ALP, IL-6, VEGF, BMP-2, OCN and Col I in OA Obs, while markedly increased ALP, VEGF, BMP-2, OCN and Col I in normal Obs. Interestingly, formononetin markedly increased the expression of VEGF and BMP-2 for 3days of culture and significantly increased OCN and Col I at 14days in human normal Obs. The remodeling effect of formononetin on osteogenic markers and cytokines of inflammatory mediators was more striking in OA Obs as well. Taken together, these results could suggest that formononetin has biphasic positive effects on normal Obs and OA Obs by modifying their biological synthetic capacities. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

Sequential contrast-enhanced MR imaging of the penis.

PubMed

Kaneko, K; De Mouy, E H; Lee, B E

1994-04-01

To determine the enhancement patterns of the penis at magnetic resonance (MR) imaging. Sequential contrast material-enhanced MR images of the penis in a flaccid state were obtained in 16 volunteers (12 with normal penile function and four with erectile dysfunction). Subjects with normal erectile function showed gradual and centrifugal enhancement of the corpora cavernosa, while those with erectile dysfunction showed poor enhancement with abnormal progression. Sequential contrast-enhanced MR imaging provides additional morphologic information for the evaluation of erectile dysfunction.

PROTEIN METABOLISM AND EXCHANGE AS INFLUENCED BY CONSTRICTION OF THE VENA CAVA

PubMed Central

McKee, Frank W.; Hyatt, Robert E.; Wilt, William G.; Tishkoff, Garson H.; Whipple, George H.

1949-01-01

Further studies of ascitic fluid production and related factors in dogs with constriction of the vena cava above the diaphragm are reported. Whole dog plasma given intravenously to such animals produces a rise in circulating plasma protein to normal levels, but increases the output of ascitic fluid with a loss of protein via the ascites equivalent to 72, 76, and 65 per cent respectively, of the injected protein. Forced ingestion of water in excess of the test animal's normal needs and desires produces no significant changes in the circulating plasma protein level or in ascitic fluid production. Amino acid growth mixtures given intravenously in distilled water cause weight loss, elevation of circulating plasma proteins, a slightly negative nitrogen balance, but no ascitic fluid production. Amino acid growth mixtures given intravenously in normal saline cause depression of the circulating plasma proteins, negative nitrogen balance, and significant ascitic fluid production. Ascitic fluid given intravenously to the test animals causes a marked depression of circulating plasma proteins, a marked increase in ascitic fluid production containing the equivalent of 116 and 98 per cent of the injected protein, and a negative nitrogen balance. Ascitic fluid given orally produces a marked depression of circulating plasma proteins, and a marked increase in ascitic fluid secretion, containing the equivalent of 66, 66, and 54 per cent respectively, of the ingested protein. Sodium chloride is a dominant factor in some of these experiments where abundant ascites production is recorded. Protein levels and intake are important, but take second place to sodium. Ascitic fluids show electrophoretic patterns which are almost identical to the plasma patterns. The A/G ratios are often equal in ascitic fluid and plasma, sometimes even lower in the ascitic fluid. This emphasizes the ease with which globulins pass cell or other membrane barriers in these experiments. PMID:18143588

Histone 3 lysine 9 acetylation is a biomarker of the effects of culture on zygotes

PubMed Central

Rollo, C; Li, Y; Jin, X L

2017-01-01

Acetylation of histone proteins is a major determinant of chromatin structure and function. Fertilisation triggers a round of chromatin remodelling that prepares the genome for the first round of transcription from the new embryonic genome. In this study we confirm that fertilisation leads to a marked progressive increase in the level of histone 3 lysine 9 acetylation in both the paternally and maternally derived genomes. The culture of zygotes in simple defined media caused a marked increase in the global level of acetylation and this affected the male pronucleus more than the female. The culture created a marked asymmetry in staining between the two pronuclei that was not readily detected in zygotes collected directly from the reproductive tract and was ameliorated to some extent by optimized culture media. The increased acetylation caused by culture resulted in increased transcription of Hspa1b, a marker of embryonic genome activation. Pharmacological analyses showed the hyperacetylation of H3K9 and the increased expression of Hspa1b caused by culture were due to the altered net activity of a range of histone acetylases and deacetylases. The marked hyperacetylation of histone 3 lysine 9 caused by culture of zygotes may serve as an early biomarker for the effects of culture on the normal function of the embryo. The results also provide further evidence for an effect of the stresses associated with assisted reproductive technologies on the normal patterns of epigenetic reprogramming in the early embryo. PMID:28878090

Lenalidomide induces lipid raft assembly to enhance erythropoietin receptor signaling in myelodysplastic syndrome progenitors.

PubMed

McGraw, Kathy L; Basiorka, Ashley A; Johnson, Joseph O; Clark, Justine; Caceres, Gisela; Padron, Eric; Heaton, Ruth; Ozawa, Yukiyasu; Wei, Sheng; Sokol, Lubomir; List, Alan F

2014-01-01

Anemia remains the principal management challenge for patients with lower risk Myelodysplastic Syndromes (MDS). Despite appropriate cytokine production and cellular receptor display, erythropoietin receptor (EpoR) signaling is impaired. We reported that EpoR signaling is dependent upon receptor localization within lipid raft microdomains, and that disruption of raft integrity abolishes signaling capacity. Here, we show that MDS erythroid progenitors display markedly diminished raft assembly and smaller raft aggregates compared to normal controls (p = 0.005, raft number; p = 0.023, raft size). Because lenalidomide triggers raft coalescence in T-lymphocytes promoting immune synapse formation, we assessed effects of lenalidomide on raft assembly in MDS erythroid precursors and UT7 cells. Lenalidomide treatment rapidly induced lipid raft formation accompanied by EpoR recruitment into raft fractions together with STAT5, JAK2, and Lyn kinase. The JAK2 phosphatase, CD45, a key negative regulator of EpoR signaling, was displaced from raft fractions. Lenalidomide treatment prior to Epo stimulation enhanced both JAK2 and STAT5 phosphorylation in UT7 and primary MDS erythroid progenitors, accompanied by increased STAT5 DNA binding in UT7 cells, and increased erythroid colony forming capacity in both UT7 and primary cells. Raft induction was associated with F-actin polymerization, which was blocked by Rho kinase inhibition. These data indicate that deficient raft integrity impairs EpoR signaling, and provides a novel strategy to enhance EpoR signal fidelity in non-del(5q) MDS.

Lenalidomide Induces Lipid Raft Assembly to Enhance Erythropoietin Receptor Signaling in Myelodysplastic Syndrome Progenitors

PubMed Central

McGraw, Kathy L.; Basiorka, Ashley A.; Johnson, Joseph O.; Clark, Justine; Caceres, Gisela; Padron, Eric; Heaton, Ruth; Ozawa, Yukiyasu; Wei, Sheng; Sokol, Lubomir; List, Alan F.

2014-01-01

Anemia remains the principal management challenge for patients with lower risk Myelodysplastic Syndromes (MDS). Despite appropriate cytokine production and cellular receptor display, erythropoietin receptor (EpoR) signaling is impaired. We reported that EpoR signaling is dependent upon receptor localization within lipid raft microdomains, and that disruption of raft integrity abolishes signaling capacity. Here, we show that MDS erythroid progenitors display markedly diminished raft assembly and smaller raft aggregates compared to normal controls (p = 0.005, raft number; p = 0.023, raft size). Because lenalidomide triggers raft coalescence in T-lymphocytes promoting immune synapse formation, we assessed effects of lenalidomide on raft assembly in MDS erythroid precursors and UT7 cells. Lenalidomide treatment rapidly induced lipid raft formation accompanied by EpoR recruitment into raft fractions together with STAT5, JAK2, and Lyn kinase. The JAK2 phosphatase, CD45, a key negative regulator of EpoR signaling, was displaced from raft fractions. Lenalidomide treatment prior to Epo stimulation enhanced both JAK2 and STAT5 phosphorylation in UT7 and primary MDS erythroid progenitors, accompanied by increased STAT5 DNA binding in UT7 cells, and increased erythroid colony forming capacity in both UT7 and primary cells. Raft induction was associated with F-actin polymerization, which was blocked by Rho kinase inhibition. These data indicate that deficient raft integrity impairs EpoR signaling, and provides a novel strategy to enhance EpoR signal fidelity in non-del(5q) MDS. PMID:25469886

A novel biological function of soluble biglycan: Induction of erythropoietin production and polycythemia.

PubMed

Frey, Helena; Moreth, Kristin; Hsieh, Louise Tzung-Harn; Zeng-Brouwers, Jinyang; Rathkolb, Birgit; Fuchs, Helmut; Gailus-Durner, Valérie; Iozzo, Renato V; de Angelis, Martin Hrabě; Schaefer, Liliana

2017-06-01

Secondary polycythemia, a disease characterized by a selective increase in circulating mature erythrocytes, is caused by enhanced erythropoietin (Epo) concentrations triggered by hypoxia-inducible factor-2α (HIF-2α). While mechanisms of hypoxia-dependent stabilization of HIF-2α protein are well established, data regarding oxygen-independent regulation of HIF-2α are sparse. In this study, we generated a novel transgenic mouse model, in which biglycan was constitutively overexpressed and secreted by hepatocytes (BGN Tg ), thereby providing a constant source of biglycan released into the blood stream. We discovered that although the mice were apparently normal, they harbored an increase in mature circulating erythrocytes. In addition to erythrocytosis, the BGN Tg mice showed elevated hemoglobin concentrations, hematocrit values and enhanced total iron binding capacity, revealing a clinical picture of polycythemia. In BGN Tg mice markedly enhanced Epo mRNA expression was observed in the liver and kidney, while elevated Epo protein levels were found in liver, kidney and blood. Mechanistically, we showed that the transgenic animals had an abundance of HIF-2α protein in the liver and kidney. Finally, by transiently overexpressing circulating biglycan in mice deficient in various Toll-like receptors (TLRs), we determined that this novel function of biglycan to promote Epo synthesis was specifically mediated by a selective interaction with TLR2. Thus, we discovered a novel biological pathway of soluble biglycan inducing HIF-2α protein stabilization and Epo production presumably in an oxygen-independent manner, ultimately giving rise to secondary polycythemia.

High-Pressure Study of the Ground- and Superconducting-State Properties of CeAu2Si2

NASA Astrophysics Data System (ADS)

Scheerer, Gernot W.; Giriat, Gaétan; Ren, Zhi; Lapertot, Gérard; Jaccard, Didier

2017-06-01

The pressure-temperature phase diagram of the new heavy-fermion superconductor CeAu2Si2 is markedly different from those studied previously. Indeed, superconductivity emerges not on the verge but deep inside the magnetic phase, and mysteriously Tc increases with the strengthening of magnetism. In this context, we have carried out ac calorimetry, resistivity, and thermoelectric power measurements on a CeAu2Si2 single crystal under high pressure. We uncover a strong link between the enhancement of superconductivity and quantum-critical-like features in the normal-state resistivity. Non-Fermi-liquid behavior is observed around the maximum of superconductivity and enhanced scattering rates are observed close to both the emergence and the maximum of superconductivity. Furthermore we observe signatures of pressure- and temperature-driven modifications of the magnetic structure inside the antiferromagnetic phase. A comparison of the features of CeAu2Si2 and its parent compounds CeCu2Si2 and CeCu2Ge2 plotted as function of the unit-cell volume leads us to propose that critical fluctuations of a valence crossover play a crucial role in the superconducting pairing mechanism. Our study illustrates the complex interplay between magnetism, valence fluctuations, and superconductivity.

Aseptic hydroponics to assess rhamnolipid-Cd and rhamnolipid-Zn bioavailability for sunflower (Helianthus annuus): a phytoextraction mechanism study.

PubMed

Wen, Jia; McLaughlin, Mike J; Stacey, Samuel P; Kirby, Jason K

2016-11-01

The availability of cadmium (Cd) and zinc (Zn) to sunflower (Helianthus annuus) was investigated in rhamnolipid- and ethylenediaminetetraacetic acid (EDTA)-buffered solutions in order to evaluate the influence of aqueous speciation of the metals on their uptake by the plant, in relation to predictions of uptake by the free ion activity model (FIAM). Free metal ion activity was estimated using the chemical equilibrium program MINTEQ or measured by Donnan dialysis. The uptake of Cd followed the FIAM for the EDTA-buffered solution at EDTA concentrations below 0.4 μM; for the rhamnolipid-buffered solution, the uptake of both metals in roots was not markedly affected by increasing rhamnolipid concentrations in solution. This suggests rhamnolipid enhanced metal accumulation in plant roots (per unit free metal in solution) possibly through formation and uptake of lipophilic complexes. The addition of normal Ca concentrations (low millimetre range) to the rhamnolipid uptake solutions reduced Cd accumulation in shoots by inhibiting Cd translocation, whereas it significantly increased Zn accumulation in shoots. This study confirms that although rhamnolipid could enhance accumulation of Cd in plants roots at low Ca supply, it is not suitable for Cd phytoextraction in contaminated soil environments where Ca concentrations in soil solution are orders of magnitude greater than those of Cd.

Defective removal of ribonucleotides from DNA promotes systemic autoimmunity

PubMed Central

Günther, Claudia; Kind, Barbara; Reijns, Martin A.M.; Berndt, Nicole; Martinez-Bueno, Manuel; Wolf, Christine; Tüngler, Victoria; Chara, Osvaldo; Lee, Young Ae; Hübner, Norbert; Bicknell, Louise; Blum, Sophia; Krug, Claudia; Schmidt, Franziska; Kretschmer, Stefanie; Koss, Sarah; Astell, Katy R.; Ramantani, Georgia; Bauerfeind, Anja; Morris, David L.; Cunninghame Graham, Deborah S.; Bubeck, Doryen; Leitch, Andrea; Ralston, Stuart H.; Blackburn, Elizabeth A.; Gahr, Manfred; Witte, Torsten; Vyse, Timothy J.; Melchers, Inga; Mangold, Elisabeth; Nöthen, Markus M.; Aringer, Martin; Kuhn, Annegret; Lüthke, Kirsten; Unger, Leonore; Bley, Annette; Lorenzi, Alice; Isaacs, John D.; Alexopoulou, Dimitra; Conrad, Karsten; Dahl, Andreas; Roers, Axel; Alarcon-Riquelme, Marta E.; Jackson, Andrew P.; Lee-Kirsch, Min Ae

2014-01-01

Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in the genes encoding the genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder that shares features with the autoimmune disease systemic lupus erythematosus (SLE). Here we determined that heterozygous parents of AGS patients exhibit an intermediate autoimmune phenotype and demonstrated a genetic association between rare RNASEH2 sequence variants and SLE. Evaluation of patient cells revealed that SLE- and AGS-associated mutations impair RNase H2 function and result in accumulation of ribonucleotides in genomic DNA. The ensuing chronic low level of DNA damage triggered a DNA damage response characterized by constitutive p53 phosphorylation and senescence. Patient fibroblasts exhibited constitutive upregulation of IFN-stimulated genes and an enhanced type I IFN response to the immunostimulatory nucleic acid polyinosinic:polycytidylic acid and UV light irradiation, linking RNase H2 deficiency to potentiation of innate immune signaling. Moreover, UV-induced cyclobutane pyrimidine dimer formation was markedly enhanced in ribonucleotide-containing DNA, providing a mechanism for photosensitivity in RNase H2–associated SLE. Collectively, our findings implicate RNase H2 in the pathogenesis of SLE and suggest a role of DNA damage–associated pathways in the initiation of autoimmunity. PMID:25500883

Topical Application of Trisodium Ascorbyl 6-Palmitate 2-Phosphate Actively Supplies Ascorbate to Skin Cells in an Ascorbate Transporter-Independent Manner

PubMed Central

Shibuya, Shuichi; Sakaguchi, Ikuyo; Ito, Shintaro; Kato, Eiko; Watanabe, Kenji; Izuo, Naotaka; Shimizu, Takahiko

2017-01-01

Ascorbic acid (AA) possesses multiple beneficial functions, such as regulating collagen biosynthesis and redox balance in the skin. AA derivatives have been developed to overcome this compound’s high fragility and to assist with AA supplementation to the skin. However, how AA derivatives are transferred into cells and converted to AA in the skin remains unclear. In the present study, we showed that AA treatment failed to increase the cellular AA level in the presence of AA transporter inhibitors, indicating an AA transporter-dependent action. In contrast, torisodium ascorbyl 6-palmitate 2-phosphate (APPS) treatment significantly enhanced the cellular AA level in skin cells despite the presence of inhibitors. In ex vivo experiments, APPS treatment also increased the AA content in a human epidermis model. Interestingly, APPS was readily metabolized and converted to AA in keratinocyte lysates via an intrinsic mechanism. Furthermore, APPS markedly repressed the intracellular superoxide generation and promoted viability associated with an enhanced AA level in Sod1-deficient skin cells. These findings indicate that APPS effectively restores the AA level and normalizes the redox balance in skin cells in an AA transporter-independent manner. Topical treatment of APPS is a beneficial strategy for supplying AA and improving the physiology of damaged skin. PMID:28640219

Functional capacity and cryopreservation of fetal rat pancreas in streptozotocin-diabetes. [Effectiveness of transplantation of fetal pancreas for control of diabetes in adult rats

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

Brown, J.; Clark, W.; Molnar, I.G.

1976-01-01

The fetal rat pancreas has a marked capacity for growth and maturation in glucose responsivity after transplantation under the kidney capsules of adult rats. The optimal conditions for function of the organ are a 3-week period of growth in a normal rat before transfer to a diabetic animal. Under these conditions diabetes is completely reversed by one fetal pancreas, and glucose disappearance rate and plasma insulin response to glucose are normal. Shunting of the venous drainage into the liver from fetal pancreases placed beneath the kidney capsule results in a marked improvement in diabetes control, and this technique may provemore » useful in experimental or human applications. Cryopreservation of the fetal pancreas has been successfully accomplished and will serve as a useful adjuvant to this method of reversing experimental diabetes.« less

Beneficial effects of low dose Musa paradisiaca on the semen quality of male Wistar rats

PubMed Central

Alabi, A. S.; Omotoso, Gabriel O.; Enaibe, B. U.; Akinola, O. B.; Tagoe, C. N. B.

2013-01-01

Background: This study aimed at determining the effects of administration of mature green fruits of Musa paradisiaca on the semen quality of adult male Wistar rats. Materials and Methods: The animals used for the study were grouped into three: the control group, given 2 ml of double distilled water, a low dose group given 500 mg/kg/day and a high dose group given 1000 mg/kg/day of the plantain fruits, which was made into flour, and dissolved in 2 ml of double distilled water for easy oral administration. Results: Significant increment in the semen parameters was noticed in animals that received a lower dose of the plantain flour, but those animals who received the high dose had marked and very significant reduction in sperm cell concentration and percentage of morphologically normal spermatozoa. Conclusion: Musa paradisiaca should be consumed in moderate quantities in order to derive its beneficial effects of enhancing male reproductive functions. PMID:23798793

Technical devices for hearing-impaired individuals: cochlear implants and brain stem implants - developments of the last decade

PubMed Central

Müller, Joachim

2005-01-01

Over the past two decades, the fascinating possibilities of cochlear implants for congenitally deaf or deafened children and adults developed tremendously and created a rapidly developing interdisciplinary research field. The main advancements of cochlear implantation in the past decade are marked by significant improvement of hearing and speech understanding in CI users. These improvements are attributed to the enhancement of speech coding strategies. The Implantation of more (and increasingly younger) children as well as the possibilities of the restoration of binaural hearing abilities with cochlear implants reflect the high standards reached by this development. Despite this progress, modern cochlear implants do not yet enable normal speech understanding, not even for the best patients. In particular speech understanding in noise remains problematic [1]. Until the mid 1990ies research concentrated on unilateral implantation. Remarkable and effective improvements have been made with bilateral implantation since 1996. Nowadays an increasing numbers of patients enjoy these benefits. PMID:22073052

Technical devices for hearing-impaired individuals: cochlear implants and brain stem implants - developments of the last decade.

PubMed

Müller, Joachim

2005-01-01

Over the past two decades, the fascinating possibilities of cochlear implants for congenitally deaf or deafened children and adults developed tremendously and created a rapidly developing interdisciplinary research field.The main advancements of cochlear implantation in the past decade are marked by significant improvement of hearing and speech understanding in CI users. These improvements are attributed to the enhancement of speech coding strategies.The Implantation of more (and increasingly younger) children as well as the possibilities of the restoration of binaural hearing abilities with cochlear implants reflect the high standards reached by this development. Despite this progress, modern cochlear implants do not yet enable normal speech understanding, not even for the best patients. In particular speech understanding in noise remains problematic [1]. Until the mid 1990ies research concentrated on unilateral implantation. Remarkable and effective improvements have been made with bilateral implantation since 1996. Nowadays an increasing numbers of patients enjoy these benefits.

Serum from CCl4-induced acute rat injury model induces differentiation of ADSCs towards hepatic cells and reduces liver fibrosis.

PubMed

Baig, Maria Tayyab; Ali, Gibran; Awan, Sana Javaid; Shehzad, Umara; Mehmood, Azra; Mohsin, Sadia; Khan, Shaheen N; Riazuddin, Sheikh

2017-10-01

Cellular therapies hold promise to alleviate liver diseases. This study explored the potential of allogenic serum isolated from rat with acute CCl 4 injury to differentiate adipose derived stem cells (ADSCs) towards hepatic lineage. Acute liver injury was induced by CCl 4 which caused significant increase in serum levels of VEGF, SDF1α and EGF. ADSCs were preconditioned with 3% serum isolated from normal and acute liver injury models. ADSCs showed enhanced expression of hepatic markers (AFP, albumin, CK8 and CK19). These differentiated ADSCs were transplanted intra-hepatically in CCl 4 -induced liver fibrosis model. After one month of transplantation, fibrosis and liver functions (alkaline phosphatase, ALAT and bilirubin) showed marked improvement in acute injury group. Elevated expression of hepatic (AFP, albumin, CK 18 and HNF4a) and pro survival markers (PCNA and VEGF) and improvement in liver architecture as deduced from results of alpha smooth muscle actin, Sirius red and Masson's trichome staining was observed.

The young skater.

PubMed

Smith, A D

2000-10-01

Figure skating is one of the best lifetime sports. Participants may skate alone or with a group, recreationally or competitively, at all ages and at all skill levels. As a sport that improves physical fitness, skating builds strength, flexibility, and cardiopulmonary endurance. As a weight-bearing or high-impact activity, it is one of the best sports for increasing bone mineral density and perhaps for preventing osteoporosis. At least half of all competitive figure skating injuries appear preventable. Boots should be as flexible as the skater can control and should be carefully fitted. Normal flexibility of lower extremity muscles, especially in the growing athlete, markedly decreases the incidence of overuse symptoms of the knee. Core body strength is critical for controlling high-impact jump landings and decreasing injuries to the spine, pelvis, and hip girdle. Adequate shoulder strength is required for pair skaters and ice dancers. A well-designed off-ice training program decreases injury incidence and enhances performance. Assisting these dedicated athletes is truly rewarding as they train and compete at their highest potential, with passion for their sport.

[Sodium restriction during pregnancy: an outdated advice].

PubMed

de Leeuw, P W; Peeters, L L

1999-10-23

Even in an early phase of pregnancy marked haemodynamic changes occur, including a fall in vascular resistance and blood pressure and a rise in cardiac output. To compensate for the increased intravascular capacity the kidney retains more sodium and water. Apparently, the set point of sodium homeostasis shifts to a higher level at the expense of an expansion of extracellular volume. Studies during the normal menstrual cycle have shown that these changes, albeit smaller, also occur during the luteal phase. These fluctuations with the menstrual cycle are less apparent if salt intake is low, suggesting that a high salt intake is needed to facilitate the process of sodium retention. In pregnancies complicated by hypertension and/or pre-eclampsia body fluid volumes are low with an enhanced tendency to retain sodium after a volume challenge. These data, together with the lack of an apparent benefit of sodium restriction, suggest that the practice of prescribing a low-salt diet to hypertensive pregnant women should be abandoned.

Stent Implantation for Malignant Pulmonary Artery Stenosis in a Metastasizing Non-Small Cell Bronchial Carcinoma

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

Gutzeit, A., E-mail: andreas.gutzeit@ksw.c; Koch, S.; Meier, U. R.

2008-07-15

A 58-year-old patient with recently diagnosed non-small cell bronchial carcinoma was referred to us with increasing shortness of breath and orthopnea by her family practitioner. To exclude the possibility of a pulmonary embolism, contrast medium-enhanced angio-CT of the thorax was performed. This showed a large mediastinal tumor, which, on the one hand, infiltrated and occluded the left upper lobe bronchus and, on the other, constricted the left pulmonary artery over a considerable part of its length. In view of the palliative situation and massively increasing dyspnea, balloon dilatation of the obstructed left pulmonary artery followed by stent placement was performed.more » This resulted in an immediate improvement of the symptoms. The originally strongly oxygen-dependent and heavily dyspneic patient could be relieved of the external supply of oxygen and was able to sleep normally without additional medication within 24 h. The patient was able ambulate freely within 2 days, with a markedly improved quality of life.« less

Evidence for carrier localization in the pseudogap state of cuprate superconductors from coherent quench experiments

PubMed Central

Madan, I.; Kurosawa, T.; Toda, Y.; Oda, M.; Mertelj, T.; Mihailovic, D.

2015-01-01

A ‘pseudogap' was introduced by Mott to describe a state of matter that has a minimum in the density of states at the Fermi level, deep enough for states to become localized. It can arise either from Coulomb repulsion between electrons, and/or incipient charge or spin order. Here we employ ultrafast spectroscopy to study dynamical properties of the normal to pseudogap state transition in the prototype high-temperature superconductor Bi2Sr2CaCu2O8+δ. We perform a systematic temperature and doping dependence study of the pseudogap photodestruction and recovery in coherent quench experiments, revealing marked absence of critical behaviour of the elementary excitations, which implies an absence of collective electronic ordering beyond a few coherence lengths on short timescales. The data imply ultrafast carrier localization into a textured polaronic state arising from a competing Coulomb interaction and lattice strain, enhanced by a Fermi surface instability. PMID:25891310

Psychosocial support for trauma-affected students after school shootings in Finland.

PubMed

Turunen, Tuija; Punamäki, Raija-Leena

2014-01-01

In Finland, as many as 20 people have lost their lives in two school shootings within one year. This article describes trauma-theoretical rationale, planning, and implementation of acute and long-term psychosocial aftercare that was organized in Kauhajoki where one of the school shootings happened. The aftercare was embedded in the school community's everyday life to enhance easy access. The aftercare proceeded in 6 phases, involving the immediate support phase at the first 24 hr, the acute phase for the first 2 weeks, followed by a 5-month period of empowerment, normalization, and creating "a safe place." The habituation phase coincided with the completion of the renovation of the damaged school building and students returning to the scene. The first anniversary was marked by shared rituals and remembrance, and the follow-up phase lasted until the end of the aftercare in 2 years. The aftercare contained, for example, psychoeducation, screening, and services at community, group, and individual levels.

Multiplexing clonality: combining RGB marking and genetic barcoding

PubMed Central

Cornils, Kerstin; Thielecke, Lars; Hüser, Svenja; Forgber, Michael; Thomaschewski, Michael; Kleist, Nadja; Hussein, Kais; Riecken, Kristoffer; Volz, Tassilo; Gerdes, Sebastian; Glauche, Ingmar; Dahl, Andreas; Dandri, Maura; Roeder, Ingo; Fehse, Boris

2014-01-01

RGB marking and DNA barcoding are two cutting-edge technologies in the field of clonal cell marking. To combine the virtues of both approaches, we equipped LeGO vectors encoding red, green or blue fluorescent proteins with complex DNA barcodes carrying color-specific signatures. For these vectors, we generated highly complex plasmid libraries that were used for the production of barcoded lentiviral vector particles. In proof-of-principle experiments, we used barcoded vectors for RGB marking of cell lines and primary murine hepatocytes. We applied single-cell polymerase chain reaction to decipher barcode signatures of individual RGB-marked cells expressing defined color hues. This enabled us to prove clonal identity of cells with one and the same RGB color. Also, we made use of barcoded vectors to investigate clonal development of leukemia induced by ectopic oncogene expression in murine hematopoietic cells. In conclusion, by combining RGB marking and DNA barcoding, we have established a novel technique for the unambiguous genetic marking of individual cells in the context of normal regeneration as well as malignant outgrowth. Moreover, the introduction of color-specific signatures in barcodes will facilitate studies on the impact of different variables (e.g. vector type, transgenes, culture conditions) in the context of competitive repopulation studies. PMID:24476916

Electromagnetic energy vortex associated with sub-wavelength plasmonic Taiji marks.

PubMed

Chen, Wei Ting; Wu, Pin Chieh; Chen, Chen Jung; Chung, Hung-Yi; Chau, Yuan-Fong; Kuan, Chieh-Hsiung; Tsai, Din Ping

2010-09-13

The Taiji symbol is a very old schematic representation of two opposing but complementary patterns in oriental civilization. Using electron beam lithography, we fabricated an array of 70 × 70 gold Taiji marks with 30 nm thickness and a total area of 50 × 50 µm(2) on a fused silica substrate. The diameter of each Taiji mark is 500 nm, while the period of the array is 700 nm. Here we present experimental as well as numerical simulation results pertaining to plasmonic resonances of several Taiji nano-structures under normal illumination. We have identified a Taiji structure with a particularly interesting vortex-like Poynting vector profile, which could be attributed to the special shape and dimensions of the Taiji symbol.

Right TKR Patients Treated with Enhanced Pain and Rehabilitation Protocols Can Drive at 2 Weeks.

PubMed

Dalury, David F; Chapman, Danielle M

2018-06-20

An important milestone in the recovery following total knee replacement (TKR) is the ability to return to driving. With advances in pain control and the widespread introduction of rapid rehab programs, we hypothesized that the ability to drive would also return sooner than had been traditionally observed. In our group of consecutive right TKR patients, using a driving simulator, we showed that at the 2-week mark, 36 of the 40 patients tested had returned to their preoperative driving capabilities and the other 4 had reached baseline at 3 weeks. While the eventual decision to return to driving is complex and dependent on many factors, we conclude that one of the benefits of enhanced pain and rehab protocols is that patients undergoing right TKR can return to driving in most instances at the 2-week mark rather than the traditional 6-week mark. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.

PubMed

Demenais, Florence; Margaritte-Jeannin, Patricia; Barnes, Kathleen C; Cookson, William O C; Altmüller, Janine; Ang, Wei; Barr, R Graham; Beaty, Terri H; Becker, Allan B; Beilby, John; Bisgaard, Hans; Bjornsdottir, Unnur Steina; Bleecker, Eugene; Bønnelykke, Klaus; Boomsma, Dorret I; Bouzigon, Emmanuelle; Brightling, Christopher E; Brossard, Myriam; Brusselle, Guy G; Burchard, Esteban; Burkart, Kristin M; Bush, Andrew; Chan-Yeung, Moira; Chung, Kian Fan; Couto Alves, Alexessander; Curtin, John A; Custovic, Adnan; Daley, Denise; de Jongste, Johan C; Del-Rio-Navarro, Blanca E; Donohue, Kathleen M; Duijts, Liesbeth; Eng, Celeste; Eriksson, Johan G; Farrall, Martin; Fedorova, Yuliya; Feenstra, Bjarke; Ferreira, Manuel A; Freidin, Maxim B; Gajdos, Zofia; Gauderman, Jim; Gehring, Ulrike; Geller, Frank; Genuneit, Jon; Gharib, Sina A; Gilliland, Frank; Granell, Raquel; Graves, Penelope E; Gudbjartsson, Daniel F; Haahtela, Tari; Heckbert, Susan R; Heederik, Dick; Heinrich, Joachim; Heliövaara, Markku; Henderson, John; Himes, Blanca E; Hirose, Hiroshi; Hirschhorn, Joel N; Hofman, Albert; Holt, Patrick; Hottenga, Jouke; Hudson, Thomas J; Hui, Jennie; Imboden, Medea; Ivanov, Vladimir; Jaddoe, Vincent W V; James, Alan; Janson, Christer; Jarvelin, Marjo-Riitta; Jarvis, Deborah; Jones, Graham; Jonsdottir, Ingileif; Jousilahti, Pekka; Kabesch, Michael; Kähönen, Mika; Kantor, David B; Karunas, Alexandra S; Khusnutdinova, Elza; Koppelman, Gerard H; Kozyrskyj, Anita L; Kreiner, Eskil; Kubo, Michiaki; Kumar, Rajesh; Kumar, Ashish; Kuokkanen, Mikko; Lahousse, Lies; Laitinen, Tarja; Laprise, Catherine; Lathrop, Mark; Lau, Susanne; Lee, Young-Ae; Lehtimäki, Terho; Letort, Sébastien; Levin, Albert M; Li, Guo; Liang, Liming; Loehr, Laura R; London, Stephanie J; Loth, Daan W; Manichaikul, Ani; Marenholz, Ingo; Martinez, Fernando J; Matheson, Melanie C; Mathias, Rasika A; Matsumoto, Kenji; Mbarek, Hamdi; McArdle, Wendy L; Melbye, Mads; Melén, Erik; Meyers, Deborah; Michel, Sven; Mohamdi, Hamida; Musk, Arthur W; Myers, Rachel A; Nieuwenhuis, Maartje A E; Noguchi, Emiko; O'Connor, George T; Ogorodova, Ludmila M; Palmer, Cameron D; Palotie, Aarno; Park, Julie E; Pennell, Craig E; Pershagen, Göran; Polonikov, Alexey; Postma, Dirkje S; Probst-Hensch, Nicole; Puzyrev, Valery P; Raby, Benjamin A; Raitakari, Olli T; Ramasamy, Adaikalavan; Rich, Stephen S; Robertson, Colin F; Romieu, Isabelle; Salam, Muhammad T; Salomaa, Veikko; Schlünssen, Vivi; Scott, Robert; Selivanova, Polina A; Sigsgaard, Torben; Simpson, Angela; Siroux, Valérie; Smith, Lewis J; Solodilova, Maria; Standl, Marie; Stefansson, Kari; Strachan, David P; Stricker, Bruno H; Takahashi, Atsushi; Thompson, Philip J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tiesler, Carla M T; Torgerson, Dara G; Tsunoda, Tatsuhiko; Uitterlinden, André G; van der Valk, Ralf J P; Vaysse, Amaury; Vedantam, Sailaja; von Berg, Andrea; von Mutius, Erika; Vonk, Judith M; Waage, Johannes; Wareham, Nick J; Weiss, Scott T; White, Wendy B; Wickman, Magnus; Widén, Elisabeth; Willemsen, Gonneke; Williams, L Keoki; Wouters, Inge M; Yang, James J; Zhao, Jing Hua; Moffatt, Miriam F; Ober, Carole; Nicolae, Dan L

2018-01-01

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.

Uninstructed BIAT faking when ego depleted or in normal state: differential effect on brain and behavior.

PubMed

Wolff, Wanja; Schindler, Sebastian; Englert, Christoph; Brand, Ralf; Kissler, Johanna

2016-05-03

Deception can distort psychological tests on socially sensitive topics. Understanding the cerebral processes that are involved in such faking can be useful in detection and prevention of deception. Previous research shows that faking a brief implicit association test (BIAT) evokes a characteristic ERP response. It is not yet known whether temporarily available self-control resources moderate this response. We randomly assigned 22 participants (15 females, 24.23 ± 2.91 years old) to a counterbalanced repeated-measurements design. Participants first completed a Brief-IAT (BIAT) on doping attitudes as a baseline measure and were then instructed to fake a negative doping attitude both when self-control resources were depleted and non-depleted. Cerebral activity during BIAT performance was assessed using high-density EEG. Compared to the baseline BIAT, event-related potentials showed a first interaction at the parietal P1, while significant post hoc differences were found only at the later occurring late positive potential. Here, significantly decreased amplitudes were recorded for 'normal' faking, but not in the depletion condition. In source space, enhanced activity was found for 'normal' faking in the bilateral temporoparietal junction. Behaviorally, participants were successful in faking the BIAT successfully in both conditions. Results indicate that temporarily available self-control resources do not affect overt faking success on a BIAT. However, differences were found on an electrophysiological level. This indicates that while on a phenotypical level self-control resources play a negligible role in deliberate test faking the underlying cerebral processes are markedly different.

Pure word deafness with auditory object agnosia after bilateral lesion of the superior temporal sulcus.

PubMed

Gutschalk, Alexander; Uppenkamp, Stefan; Riedel, Bernhard; Bartsch, Andreas; Brandt, Tobias; Vogt-Schaden, Marlies

2015-12-01

Based on results from functional imaging, cortex along the superior temporal sulcus (STS) has been suggested to subserve phoneme and pre-lexical speech perception. For vowel classification, both superior temporal plane (STP) and STS areas have been suggested relevant. Lesion of bilateral STS may conversely be expected to cause pure word deafness and possibly also impaired vowel classification. Here we studied a patient with bilateral STS lesions caused by ischemic strokes and relatively intact medial STPs to characterize the behavioral consequences of STS loss. The patient showed severe deficits in auditory speech perception, whereas his speech production was fluent and communication by written speech was grossly intact. Auditory-evoked fields in the STP were within normal limits on both sides, suggesting that major parts of the auditory cortex were functionally intact. Further studies showed that the patient had normal hearing thresholds and only mild disability in tests for telencephalic hearing disorder. Prominent deficits were discovered in an auditory-object classification task, where the patient performed four standard deviations below the control group. In marked contrast, performance in a vowel-classification task was intact. Auditory evoked fields showed enhanced responses for vowels compared to matched non-vowels within normal limits. Our results are consistent with the notion that cortex along STS is important for auditory speech perception, although it does not appear to be entirely speech specific. Formant analysis and single vowel classification, however, appear to be already implemented in auditory cortex on the STP. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thrombin-stimulated platelet aggregation is inhibited by kallikrein in a time- and concentration-dependent manner.

PubMed

Veloso, D

2003-01-01

Many in vitro studies have shown that activation of prekallikrein (PK) to kallikrein (KAL) in normal plasma triggers rapid activation of the coagulation cascade. In agreement, the coagulation activation is impaired in PK-deficient plasma. Paradoxically, PK-deficient patients show a tendency to thrombosis. To investigate the discrepancy between the in vitro and in vivo findings, we analyzed the effect of KAL on the rate of platelet aggregation. For this research, physiologic concentrations of washed human platelets were incubated for 5 and/or 10 min with approximately 2.2 to 88 nM human plasma KAL (< 1/100 to approximately 1/3 of PK concentrations in plasma) prior to the addition of high concentrations of alpha-thrombin (54 nM) or fibrinogen plus ADP. KAL concentrations were arbitrarily selected on the assumption that concentrations of free KAL (the enzymatically active species) were minute in normal plasma and higher when KAL production was enhanced, and/or inhibitors were depleted. Full platelet aggregation was that seen in the absence of KAL or PK. Inhibition of platelet aggregation stimulated by thrombin was markedly increased with increased KAL concentrations and incubation times. The degree of inhibition by KAL was smaller when ADP was the agonist. The data suggest that KAL may play a role in the modulation of platelet aggregation in vivo under normal conditions as well as when prolonged, high concentrations of KAL occur in blood. The data may also help to explain the intriguing observation that PK-deficient patients show a tendency to thrombotic episodes and myocardial infarction whereas in vitro assays predict bleeding.

Influence of thermal anisotropy on best-fit estimates of shock normals

NASA Technical Reports Server (NTRS)

Lepping, R. P.

1971-01-01

The influence of thermal anisotropy on the estimates of interplanetary shock parameters and the associated normals is discussed. A practical theorem is presented for quantitatively correcting for anisotropic effects by weighting the before and after magnetic fields by the same anisotropy parameter h. The quantity h depends only on the thermal anisotropies before and after the shock and on the angles between the magnetic fields and the shock normal. The theorem can be applied to most slow shocks, but in those cases h usually should be lower, and sometimes markedly lower, than unity. For the extreme values of h, little change results in the shock parameters or in the shock normal.

An Inherited Platelet Function Defect in Basset Hounds

PubMed Central

Johnstone, I. B.; Lotz, F.

1979-01-01

An inherited platelet function defect occurring in a family of basset hounds has been described. The trait is transmitted as an autosomal characteristic and appears to be expressed clinically only in the homozygous state. The characteristics of this platelet defect include: 1) marked bleeding tendencies and prolonged skin bleeding times in either male or female dogs. 2) normal blood coagulation mechanism. 3) adequate numbers of circulating platelets which appear morphologically normal by light microscopy. 4) normal whole blood clot retraction. 5) deficient in vivo platelet consumption and in vitro platelet retention in glass bead columns. 6) defective ADP-induced platelet aggregation in homozygotes, apparently normal ADP response in heterozygotes, and defective collagen-induced platelet aggregation in both. PMID:509382

A Spiking Strategy for ChIP-chip Data Normalization in S. cerevisiae.

PubMed

Jeronimo, Célia; Robert, François

2017-01-01

Chromatin immunoprecipitation coupled to DNA microarrays (ChIP-chip) is widely used in the chromatin field, notably to map the position of histone variants or histone modifications along the genome. Often, the position and the occupancy of these epigenetic marks are to be compared between different experiments. It is now increasingly recognized that such cross-sample comparison is better done using externally added exogenous controls for normalization but no such method has been described for ChIP-chip. Here we describe a spiking normalization strategy that makes use of phiX174 phage DNA as a spiked control for normalization of ChIP-chip signals across different experiments.

PubMed-EX: a web browser extension to enhance PubMed search with text mining features.

PubMed

Tsai, Richard Tzong-Han; Dai, Hong-Jie; Lai, Po-Ting; Huang, Chi-Hsin

2009-11-15

PubMed-EX is a browser extension that marks up PubMed search results with additional text-mining information. PubMed-EX's page mark-up, which includes section categorization and gene/disease and relation mark-up, can help researchers to quickly focus on key terms and provide additional information on them. All text processing is performed server-side, freeing up user resources. PubMed-EX is freely available at http://bws.iis.sinica.edu.tw/PubMed-EX and http://iisr.cse.yzu.edu.tw:8000/PubMed-EX/.

Imaging Characteristics of Tenosynovial and Bursal Chondromatosis

DTIC Science & Technology

2010-01-01

presence of tumor staining ( avascular , hypovascular, or hypervascular), the degree (mild, moderate, or marked) and pattern (diffuse or Skeletal Radiol...chondromatosis (T or B), and location of the lesion Skeletal Radiol fluid levels) or central necrosis (low attenuation with rim enhancement). The...enhancement following intravenous contrast if available) or central necrosis (low signal on T1, high signal on T2 with rim enhancement following intravenous

Corneal endothelial cell density and morphology in normal Filipino eyes.

PubMed

Padilla, Ma Dominga B; Sibayan, Santiago Antonio B; Gonzales, Clarissa S A

2004-03-01

To describe the corneal endothelial cell density and morphology in normal adult Filipino eyes. Specular microscopy was performed in 640 eyes of 320 normal Filipino volunteers aged 20 to 86 years. Of these, 163 were male, and 157 were female. Mean cell density (MCD), mean cell area (MCA), coefficient of variation (CV) in cell size (polymegathism), and hexagonality were recorded and analyzed in relation to fellow eyes, gender, and age. MCD was 2798 +/- 307.2 cells/mm, and MCA was 363.0 +/- 40.3 microm. Results showed that women had a MCD 7.8% greater than men (P < 0.01). Regression analysis showed a consistent decrease in MCD (r = -0.47) and increase in MCA (r = 0.45) from 20 to 60 years of age. This was followed by a marked decrease in correlation and apparent trend reversal for both variables in the groups above 60 years (MCD r = 0.18, MCA r = -0.04) accompanied by a marked increase in CV in cell size (20-60 years r = -0.04, >60 years r = 0.33). A very low negative correlation (r = -0.10) was noted between hexagonality and increasing age through all age groups. The first normative data for the endothelium of Filipino eyes are reported. There are statistically significant differences in MCD between genders, and a consistent decrease in MCD and increase in MCA with age only until 60 years old, after which correlation between age and these variables decreases. Polymegathism and correlation between CV in cell size and age markedly increase after age 60.

Enhancing Inter-Firm Networks and Interorganizational Strategies. Research in Management Consulting Series.

ERIC Educational Resources Information Center

Buono, Anthony F., Ed.

This book contain papers 13 papers on enhancing inter-firm networks, including by intervening in mergers and acquisitions and developing strategic alliances and partnerships. The following papers are included: "Introduction" (Anthony F. Buono); "Making Mergers and Acquisitions Work: A Guide to Consulting Interventions" (Mitchell Lee Marks);…

Social Role Valorization: A Proposed New Term for the Principle of Normalization

ERIC Educational Resources Information Center

Wolfensberger, Wolf

2011-01-01

The highest goal of the principle of normalization has recently been clarified to be the establishment, enhancement, or defense of the social role(s) of a person or group, via the enhancement of people's social images and personal competencies. In consequence, it is proposed that normalization be henceforth called "social role valorization."

NORMAL HUMAN VARIATION: REFOCUSSING THE ENHANCEMENT DEBATE

PubMed Central

Kahane, Guy; Savulescu, Julian

2015-01-01

This article draws attention to several common mistakes in thinking about biomedical enhancement, mistakes that are made even by some supporters of enhancement. We illustrate these mistakes by examining objections that John Harris has recently raised against the use of pharmacological interventions to directly modulate moral decision-making. We then apply these lessons to other influential figures in the debate about enhancement. One upshot of our argument is that many considerations presented as powerful objections to enhancement are really strong considerations in favour of biomedical enhancement, just in a different direction. Another upshot is that it is unfortunate that much of the current debate focuses on interventions that will radically transform normal human capacities. Such interventions are unlikely to be available in the near future, and may not even be feasible. But our argument shows that the enhancement project can still have a radical impact on human life even if biomedical enhancement operated entirely within the normal human range. PMID:23906367

Enhanced activation of the left hemisphere promotes normative decision making.

PubMed

Corser, Ryan; Jasper, John D

2014-01-01

Previous studies have reported that enhanced activation of the left cerebral hemisphere reduces risky-choice, attribute, and goal-framing effects relative to enhanced activation of the right cerebral hemisphere. The present study sought to extend these findings and show that enhanced activation of the left hemisphere also reduces violations of other normative principles, besides the invariance principle. Participants completed ratio bias (Experiment 1, N = 296) and base rate neglect problems (Experiment 2, N = 145) under normal (control) viewing or with the right or left hemisphere primarily activated by imposing a unidirectional gaze. In Experiment 1 we found that enhanced left hemispheric activation reduced the ratio bias relative to normal viewing and a group experiencing enhanced right hemispheric activation. In Experiment 2 enhanced left hemispheric activation resulted in using base rates more than normal viewing, but not significantly more than enhanced right hemispheric activation. Results suggest that hemispheric asymmetries can affect higher-order cognitive processes, such as decision-making biases. Possible theoretical accounts are discussed as well as implications for dual-process theories.

Lymphadenitis associated with cat-scratch disease simulating a neoplasm: Imaging findings with histopathological associations.

PubMed

Chen, Ying; Fu, Yan-Biao; Xu, Xiu-Fang; Pan, Yao; Lu, Chen-Ying; Zhu, Xiu-Liang; Li, Qing-Hai; Yu, Ri-Sheng

2018-01-01

The lymphadenitis associated with cat-scratch disease (CSD) is often confused with neoplasms by a number of radiologists and clinicians, and consequently, unnecessary invasive procedures or surgeries are performed. In the present study, the contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) findings of 10 patients (6 men and 4 women) with clinically and pathologically confirmed lymphadenitis associated with CSD were retrospectively analyzed (CT in 3 patients, MRI in 6 patients, and CT and MRI in 1 patient) at The Second Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China) between January 2007 and November 2014. As a result, 17 enlarged lymph nodes were identified in 10 cases. The 5 nodes identified by CT scan exhibited relatively inhomogeneous isodensity to muscle, with patchy low density in the center. All 14 nodes identified by MRI scan exhibited homogeneous or heterogeneous isointensity to muscle or slightly increased intensity compared with that of muscle on T1-weighted images (T1WI), and homogeneous or heterogeneous hyperintensity on fat-suppressed T2WI. Following enhancement, all 17 enlarged lymph nodes associated with CSD demonstrated the following 3 different enhancement patterns: Moderate homogeneous enhancement (n=8), which was associated with histologically identified early disease stage; marked heterogeneous enhancement with no enhancement of the necrotic areas (n=4), and heterogeneous enhancement with progressively 'spoke-wheel-like' (defined as radiating enhancement from the center) enhancement of the patchy low-density area (n=1), which was associated with histologically identified intermediate disease stage; and astral low-density/hypointensity with marked enhancement (n=2) or a 'rose flower' sign (n=2), which was associated with histologically identified late disease stage. We hypothesized that the CT and MRI results of lymphadenitis in CSD may be associated with the pathological features. It may be suggested that the diagnosis of CSD may be formed when considering the characteristic CT and MRI features of astral low-density/hypointensity with marked enhancement or a 'rose flower' sign (defined as marginal petaloid enhancement) in the late disease stage, or the MRI results of homogeneous, moderate enhancement in the early disease stage, or the CT/MRI data of heterogeneous enhancement with non-enhancing area in the center in the intermediate disease stage, in solitary or multiple enlarged lymph nodes associated with general subcutaneous edema in the vicinity of the nodes on CT/MRI and with a history of cat exposure.

Analysis of JSI TRIGA MARK II reactor physical parameters calculated with TRIPOLI and MCNP.

PubMed

Henry, R; Tiselj, I; Snoj, L

2015-03-01

New computational model of the JSI TRIGA Mark II research reactor was built for TRIPOLI computer code and compared with existing MCNP code model. The same modelling assumptions were used in order to check the differences of the mathematical models of both Monte Carlo codes. Differences between the TRIPOLI and MCNP predictions of keff were up to 100pcm. Further validation was performed with analyses of the normalized reaction rates and computations of kinetic parameters for various core configurations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Magnetic resonance imaging and computed tomography characteristics of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion.

PubMed

Wang, Wei; Ding, Jianhui; Li, Yuan; Wang, Chaofu; Zhou, Liangping; Zhu, Hui; Peng, Weijun

2014-01-01

To characterize Xp11.2 translocation renal cell carcinoma (RCC) using magnetic resonance imaging (MRI) and computed tomography (CT). This study retrospectively collected the MRI and CT data of twelve patients with Xp11.2 translocation RCC confirmed by pathology. Nine cases underwent dynamic contrast-enhanced MRI (DCE-MRI) and 6 cases underwent CT, of which 3 cases underwent MRI and CT simultaneously. The MRI and CT findings were analyzed in regard to tumor position, size, hemorrhagic, cystic or necrotic components, calcification, tumor density, signal intensity and enhancement features. The age of the 12 patients ranged from 13 to 46 years (mean age: 23 years). T2WI revealed heterogeneous intensity, hyper-intensity, and slight hypo-intensity in 6 cases, 2 cases, and 1 case, respectively. On DCE-MR images, mild, moderate, and marked rim enhancement of the tumor in the corticomedullary phase (CMP) were observed in 1, 6, and 2 cases, respectively. The tumor parenchyma showed iso-attenuation (n = 4) or slight hyper-attenuation (n = 1) compared to the normal renal cortex on non-contrast CT images. Imaging findings were suggestive of hemorrhage (n = 4) or necrosis (n = 8) in the tumors, and there was evidence of calcification in 8 cases by CT (n = 3) and pathology (n = 8). On dynamic contrast-enhanced CT images, 3 cases and 1 case manifested moderate and strong CMP enhancement, respectively. Nine tumors by MRI and 4 tumors by CT showed prolonged enhancement. Three neoplasms presented at stage I, 2 at stage II, 3 at stage III, and 4 at stage IV according the 2010 AJCC staging criteria. XP11.2 translocation RCC should be considered when a child or young adult patient presents with a renal tumor with heterogeneous features such as hemorrhage, necrosis, cystic changes, and calcification on CT and MRI and/or is accompanied by metastatic evidence.

Magnetic Resonance Imaging and Computed Tomography Characteristics of Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusion

PubMed Central

Li, Yuan; Wang, Chaofu; Zhou, Liangping; Zhu, Hui; Peng, Weijun

2014-01-01

Purpose To characterize Xp11.2 translocation renal cell carcinoma (RCC) using magnetic resonance imaging (MRI) and computed tomography (CT). Methods This study retrospectively collected the MRI and CT data of twelve patients with Xp11.2 translocation RCC confirmed by pathology. Nine cases underwent dynamic contrast-enhanced MRI (DCE-MRI) and 6 cases underwent CT, of which 3 cases underwent MRI and CT simultaneously. The MRI and CT findings were analyzed in regard to tumor position, size, hemorrhagic, cystic or necrotic components, calcification, tumor density, signal intensity and enhancement features. Results The age of the 12 patients ranged from 13 to 46 years (mean age: 23 years). T2WI revealed heterogeneous intensity, hyper-intensity, and slight hypo-intensity in 6 cases, 2 cases, and 1 case, respectively. On DCE-MR images, mild, moderate, and marked rim enhancement of the tumor in the corticomedullary phase (CMP) were observed in 1, 6, and 2 cases, respectively. The tumor parenchyma showed iso-attenuation (n = 4) or slight hyper-attenuation (n = 1) compared to the normal renal cortex on non-contrast CT images. Imaging findings were suggestive of hemorrhage (n = 4) or necrosis (n = 8) in the tumors, and there was evidence of calcification in 8 cases by CT (n = 3) and pathology (n = 8). On dynamic contrast-enhanced CT images, 3 cases and 1 case manifested moderate and strong CMP enhancement, respectively. Nine tumors by MRI and 4 tumors by CT showed prolonged enhancement. Three neoplasms presented at stage I, 2 at stage II, 3 at stage III, and 4 at stage IV according the 2010 AJCC staging criteria. Conclusions XP11.2 translocation RCC should be considered when a child or young adult patient presents with a renal tumor with heterogeneous features such as hemorrhage, necrosis, cystic changes, and calcification on CT and MRI and/or is accompanied by metastatic evidence. PMID:24926688

Multispectral histogram normalization contrast enhancement

NASA Technical Reports Server (NTRS)

Soha, J. M.; Schwartz, A. A.

1979-01-01

A multispectral histogram normalization or decorrelation enhancement which achieves effective color composites by removing interband correlation is described. The enhancement procedure employs either linear or nonlinear transformations to equalize principal component variances. An additional rotation to any set of orthogonal coordinates is thus possible, while full histogram utilization is maintained by avoiding the reintroduction of correlation. For the three-dimensional case, the enhancement procedure may be implemented with a lookup table. An application of the enhancement to Landsat multispectral scanning imagery is presented.

ARRB1/β-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia

PubMed Central

Wang, Pei; Xu, Tian-Ying; Wei, Kai; Guan, Yun-Feng; Wang, Xia; Xu, Hui; Su, Ding-Feng; Pei, Gang; Miao, Chao-Yu

2014-01-01

Autophagy, a highly conserved process conferring cytoprotection against stress, contributes to the progression of cerebral ischemia. β-arrestins are multifunctional proteins that mediate receptor desensitization and serve as important signaling scaffolds involved in numerous physiopathological processes. Here, we show that both ARRB1 (arrestin, β 1) and ARRB2 (arrestin, β 2) were upregulated by cerebral ischemic stress. Knockout of Arrb1, but not Arrb2, aggravated the mortality, brain infarction, and neurological deficit in a mouse model of cerebral ischemia. Accordingly, Arrb1-deficient neurons exhibited enhanced cell injury upon oxygen-glucose deprivation (OGD), an in vitro model of ischemia. Deletion of Arrb1 did not affect the cerebral ischemia-induced inflammation, oxidative stress, and nicotinamide phosphoribosyltransferase upregulation, but markedly suppressed autophagy and induced neuronal apoptosis/necrosis in vivo and in vitro. Additionally, we found that ARRB1 interacted with BECN1/Beclin 1 and PIK3C3/Vps34, 2 major components of the BECN1 autophagic core complex, under the OGD condition but not normal conditions in neurons. Finally, deletion of Arrb1 impaired the interaction between BECN1 and PIK3C3, which is a critical event for autophagosome formation upon ischemic stress, and markedly reduced the kinase activity of PIK3C3. These findings reveal a neuroprotective role for ARRB1, in the context of cerebral ischemia, centered on the regulation of BECN1-dependent autophagosome formation. PMID:24988431

Peptide YY: a potential therapy for obesity.

PubMed

Renshaw, D; Batterham, R L

2005-03-01

Obesity now represents a modern epidemic in western society with major health and economic consequences. Unfortunately, previous pharmacological approaches to the treatment of obesity have been associated with life-threatening side effects and limited efficacy. Over recent years there has been a marked increase in our understanding of the physiological mechanisms that regulate body weight and how these are perturbed in obesity. One therapeutic strategy is to develop drugs which both mimic and enhance the body's own satiety signals. The gut hormone peptide tyrosine tyrosine (PYY), which is released postprandially from the gastrointestinal tract, has recently been shown to be a physiological regulator of food intake. Peripheral administration of PYY reduces feeding in rodents via a mechanism which requires the Y2 receptor and is thought to primarily involve modulation of the hypothalamic arcuate nucleus (ARC) circuitry. In humans a single 90-minute infusion of PYY has been shown to markedly reduce subsequent 24-hour caloric intake in lean, normal-weight and obese subjects. Moreover, obese subjects have been found to have low levels of fasting and postprandial PYY suggesting a role for this hormone in the pathogenesis of obesity. Although studies examining the effects of chronic peripheral administration of PYY to humans are awaited, the results from continuous infusion studies in a number of obese rodent models are encouraging with reductions in food intake, body weight and adiposity observed. Potential therapeutic manipulations based on the PYY system include development of Y2 agonists, exogenously administration of PYY or increased endogenous release from the gastrointestinal tract.

FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential

PubMed Central

Lay, Kenneth; Kume, Tsutomu; Fuchs, Elaine

2016-01-01

Adult tissue stem cells (SCs) reside in niches, which orchestrate SC behavior. SCs are typically used sparingly and exist in quiescence unless activated for tissue growth. Whether parsimonious SC use is essential to conserve long-term tissue-regenerating potential during normal homeostasis remains poorly understood. Here, we examine this issue by conditionally ablating a key transcription factor Forkhead box C1 (FOXC1) expressed in hair follicle SCs (HFSCs). FOXC1-deficient HFSCs spend less time in quiescence, leading to markedly shortened resting periods between hair cycles. The enhanced hair cycling accelerates HFSC expenditure, and impacts hair regeneration in aging mice. Interestingly, although FOXC1-deficient HFs can still form a new bulge that houses HFSCs for the next hair cycle, the older bulge is left unanchored. As the new hair emerges, the entire old bulge, including its reserve HFSCs and SC-inhibitory inner cell layer, is lost. We trace this mechanism first, to a marked increase in cell cycle-associated transcripts upon Foxc1 ablation, and second, to a downstream reduction in E-cadherin–mediated inter-SC adhesion. Finally, we show that when the old bulge is lost with each hair cycle, overall levels of SC-inhibitory factors are reduced, further lowering the threshold for HFSC activity. Taken together, our findings suggest that HFSCs have restricted potential in vivo, which they conserve by coupling quiescence to adhesion-mediated niche maintenance, thereby achieving long-term tissue homeostasis. PMID:26912458

Bidirectional regulation of human colonic smooth muscle contractility by tachykinin NK(2) receptors.

PubMed

Nakamura, Akihiro; Tanaka, Takahiro; Imanishi, Akio; Kawamoto, Makiko; Toyoda, Masao; Mizojiri, Gaku; Tsukimi, Yasuhiro

2011-01-01

In this study, we attempted to clarify the mechanism of tachykinin-induced motor response in isolated smooth muscle preparations of the human colon. Fresh specimens of normal colon were obtained from patients suffering from colonic cancer. Using mucosa-free smooth muscle strips, smooth muscle tension with circular direction was monitored isometrically. Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) produced marked contraction. All of these contractions were inhibited by saredutant, a selective NK(2)-R antagonist, but not by CP122721, a selective NK(1)-R antagonist or talnetant, a selective NK(3)-R antagonist. βAla(8)-NKA(4-10) induced concentration-dependent contraction similar to NKA, but Sar(9)-Met(11)-SP and Met-Phe(7)-NKB did not cause marked contraction. Colonic contraction induced by βAla(8)-NKA(4-10) was completely blocked by saredutant, but not by atropine. Tetrodotoxin or N(G)-nitro-L-arginine methyl ester pretreatment significantly enhanced βAla(8)-NKA(4-10)-induced contraction. Immunohistochemical analysis showed that the NK(2)-R was expressed on the smooth muscle layers and myenteric plexus where it was also co-expressed with neuronal nitric oxide synthase in the myenteric plexus. These results suggest that the NK(2)-R is a major contributor to tachykinin-induced smooth muscle contraction in human colon and that the NK(2)-R-mediated response consists of an excitatory component via direct action on the smooth muscle and an inhibitory component possibly via nitric oxide neurons.

Somnolence and Stuttering as the Primary Manifestations of a Midbrain Stroke

PubMed Central

Karakis, Ioannis; Ellenstein, Aviva; Roselló, Gemma R; Romero, José R

2008-01-01

Background: Stroke can occasionally manifest with non-lateralizing findings such as somnolence and stuttering. We describe a case and discuss the anatomical and physiological implications of this rare combination of symptoms. Case report: A 51-year-old woman presented with 3 days of “feeling drunk”. She could further specify her symptoms as blurry vision, slurred speech, and gait instability. She had a history of hypertension and hyperlipidemia. Her examination at presentation was remarkable only for marked somnolence. Over the next several hours she developed mild upgaze limitation and vertical nystagmus. Non-enhanced computed tomography of the brain was normal. Brain magnetic resonance imaging (MRI) revealed a 5 mm acute infarct in the caudal midbrain. The first week the patient remained somnolent and manifested marked stuttering. The patient improved gradually with speech therapy. Conclusion: Strokes affecting the diencephalic-mesencephalic junction can manifest with stuttering. Defective projections of the reticular formation to the supplementary motor area, damaged extrapyramidal circuits, and/or aberrant propioceptive feedback due to involvement of the mesencephalic nucleus of the trigeminal nerve are the proposed pathophysiological mechanisms. Somnolence can also be part of the presentation and is likely due to disruptions of sleep pathways subserved by the reticular activating system. The accurate diagnosis of these cases depends on careful clinical assessment and high index of suspicion for stroke, especially in lieu of preexisting vascular risk factors and lack of an alternative explanation such as toxic-metabolic encephalopathy. PMID:22518226

Beneficial effects of naloxone in a patient with intestinal pseudoobstruction

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

Schang, J.C.; Devroede, G.

1985-06-01

A 15-day course of Naloxone treatment was given to a patient with intestinal pseudoobstruction who had previously undergone subtotal colectomy with terminal ileostomy for invalidating constipation. The effects of the drug were assessed according to symptoms, by recording the myoelectric activity of the stomach, and by measuring gastric emptying of a radiolabeled solid-liquid meal and the intestinal transit time of radiopaque markers. All tests were performed 1) at baseline; 2) after 2 wk with Naloxone 1.6 mg subcutaneous per day; and 3) after 8 days of placebo. Results showed that before treatment gastric emptying of solids was delayed, emptying ofmore » liquids was normal, myoelectric activity of the stomach was normal, small intestinal transit time of radiopaque markers was considerably increased while ileal output was markedly decreased. After Naloxone, gastric emptying of solids was markedly accelerated, emptying of liquids remained normal, gastric electrical spiking activity increased, small intestinal transit time strikingly decreased, and ileal output increased. After placebo, a tendency to return to pretreatment values was observed. This observation suggests that Naloxone may be helpful in the treatment of some patients with intestinal pseudoobstruction.« less

Physical Properties Of Acupuncture Needles: Do Disposable Acupuncture Needles Break With Normal Use

DTIC Science & Technology

2016-06-01

Lamb shank, which has complexity of tendon, fascia, and bone, was used to mimic human tissue. The needles (n=10) were stressed in the tissue substitute...needles were re-imaged after stressing and visually assessed. RESULTS: Only one manufacturing scuff mark was noted out of 90 needles before stress ...testing. Needles buckled but did not break when they were stressed beyond normal clinical use. No cracks or fractures were noted after stress

Effects of Heparin and Lisofylline on Pulmonary Function Following Smoke Inhalation Injury in an Ovine Model

DTIC Science & Technology

2002-03-01

25 mg/kg intravenously). One radiopaque sheath introducer, through which a pulmonary artery flotation catheter was placed, was inserted into an...the tracheobronchoepithelial damage score was as follows: 0, normal; 1, some loss of cilia, loss of apical epithelium; 2, marked attenuation of epi...limited to the left apical lobe be- cause bronchoalveolar lavage was done in the other lobes. The lung parenchymal damage score was as follows: 0, normal; 1

The prolyl isomerase Pin1 increases β-cell proliferation and enhances insulin secretion.

PubMed

Nakatsu, Yusuke; Mori, Keiichi; Matsunaga, Yasuka; Yamamotoya, Takeshi; Ueda, Koji; Inoue, Yuki; Mitsuzaki-Miyoshi, Keiko; Sakoda, Hideyuki; Fujishiro, Midori; Yamaguchi, Suguru; Kushiyama, Akifumi; Ono, Hiraku; Ishihara, Hisamitsu; Asano, Tomoichiro

2017-07-14

The prolyl isomerase Pin1 binds to the phosphorylated Ser/Thr-Pro motif of target proteins and enhances their cis-trans conversion. This report is the first to show that Pin1 expression in pancreatic β cells is markedly elevated by high-fat diet feeding and in ob/ob mice. To elucidate the role of Pin1 in pancreatic β cells, we generated β-cell-specific Pin1 KO (βPin1 KO) mice. These mutant mice showed exacerbation of glucose intolerance but had normal insulin sensitivity. We identified two independent factors underlying impaired insulin secretion in the βPin1 KO mice. Pin1 enhanced pancreatic β-cell proliferation, as indicated by a reduced β-cell mass in βPin1 KO mice compared with control mice. Moreover, a diet high in fat and sucrose failed to increase pancreatic β-cell growth in the βPin1 KO mice, an observation to which up-regulation of the cell cycle protein cyclin D appeared to contribute. The other role of Pin1 was to activate the insulin-secretory step: Pin1 KO β cells showed impairments in glucose- and KCl-induced elevation of the intracellular Ca 2+ concentration and insulin secretion. We also identified salt-inducible kinase 2 (SIK2) as a Pin1-binding protein that affected the regulation of Ca 2+ influx and found Pin1 to enhance SIK2 kinase activity, resulting in a decrease in p35 protein, a negative regulator of Ca 2+ influx. Taken together, our observations demonstrate critical roles of Pin1 in pancreatic β cells and that Pin1 both promotes β-cell proliferation and activates insulin secretion. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Diffuse noxious inhibitory controls and nerve injury: restoring an imbalance between descending monoamine inhibitions and facilitations.

PubMed

Bannister, Kirsty; Patel, Ryan; Goncalves, Leonor; Townson, Louisa; Dickenson, Anthony H

2015-09-01

Diffuse noxious inhibitory controls (DNICs) utilize descending inhibitory controls through poorly understood brain stem pathways. The human counterpart, conditioned pain modulation, is reduced in patients with neuropathy aligned with animal data showing a loss of descending inhibitory noradrenaline controls together with a gain of 5-HT3 receptor-mediated facilitations after neuropathy. We investigated the pharmacological basis of DNIC and whether it can be restored after neuropathy. Deep dorsal horn neurons were activated by von Frey filaments applied to the hind paw, and DNIC was induced by a pinch applied to the ear in isoflurane-anaesthetized animals. Spinal nerve ligation was the model of neuropathy. Diffuse noxious inhibitory control was present in control rats but abolished after neuropathy. α2 adrenoceptor mechanisms underlie DNIC because the antagonists, yohimbine and atipamezole, markedly attenuated this descending inhibition. We restored DNIC in spinal nerve ligated animals by blocking 5-HT3 descending facilitations with the antagonist ondansetron or by enhancing norepinephrine modulation through the use of reboxetine (a norepinephrine reuptake inhibitor, NRI) or tapentadol (μ-opioid receptor agonist and NRI). Additionally, ondansetron enhanced DNIC in normal animals. Diffuse noxious inhibitory controls are reduced after peripheral nerve injury illustrating the central impact of neuropathy, leading to an imbalance in descending excitations and inhibitions. Underlying noradrenergic mechanisms explain the relationship between conditioned pain modulation and the use of tapentadol and duloxetine (a serotonin, NRI) in patients. We suggest that pharmacological strategies through manipulation of the monoamine system could be used to enhance DNIC in patients by blocking descending facilitations with ondansetron or enhancing norepinephrine inhibitions, so possibly reducing chronic pain.

Small Cell Lung Cancer Exhibits Frequent Inactivating Mutations in the Histone Methyltransferase KMT2D/MLL2: CALGB 151111 (Alliance)

PubMed Central

Augert, Arnaud; Zhang, Qing; Bates, Breanna; Cui, Min; Wang, Xiaofei; Wildey, Gary; Dowlati, Afshin; MacPherson, David

2017-01-01

Introduction SCLC is a lethal neuroendocrine tumor type that is highly prone to metastasis. There is an urgency to understand the mutated genes that promote SCLC, as there are no approved targeted therapies yet available. SCLC is rarely resected, limiting the number of samples available for genomic analyses of somatic mutations. Methods To identify potential driver mutations in human SCLC we sequenced the whole exomes of 18 primary SCLCs and seven cell lines along with matched normal controls. We extended these data by resequencing a panel of genes across 40 primary SCLCs and 48 cell lines. Results We report frequent mutations in the lysine methyltransferase 2D gene (KMT2D) (also known as MLL2), a key regulator of transcriptional enhancer function. KMT2D exhibited truncating nonsense/frameshift/splice site mutations in 8% of SCLC tumors and 17% of SCLC cell lines. We found that KMT2D mutation in human SCLC cell lines was associated with reduced lysine methyltransferase 2D protein levels and reduced monomethylation of histone H3 lysine 4, a mark associated with transcriptional enhancers. We also found mutations in other genes associated with transcriptional enhancer control, including CREB binding protein gene (CREBBP), E1A binding protein p300 gene (EP300), and chromodomain helicase DNA binding protein 7 gene (CHD7), and we report mutations in additional chromatin remodeling genes such as polybromo 1 gene (PBRM1). Conclusions These data indicate that KMT2D is one of the major mutated genes in SCLC, and they point to perturbation of transcriptional enhancer control as potentially contributing to SCLC. PMID:28007623

Acupuncture for neurogenesis in experimental ischemic stroke: a systematic review and meta-analysis.

PubMed

Lu, Lin; Zhang, Xiao-guang; Zhong, Linda L D; Chen, Zi-xian; Li, Yan; Zheng, Guo-qing; Bian, Zhao-xiang

2016-01-20

Acupuncture has been used for patients with stroke and post-stroke rehabilitation for thousands of years. Previous studies reported that acupuncture enhanced stroke recovery through neurogenesis. Hence, we conducted a systematic review and meta-analysis for preclinical studies to assess the current evidence for acupuncture effect on neurogenesis in treating ischaemic stroke. Studies were obtained from six databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, VIP information database, and Chinese Biomedical Literature Database, Ultimately, 34 studies containing 1617 animals were identified. Neurogenesis markers of Brdu, Nestin, PSA-NCAM, NeuN and GFAP were selected as major outcomes. The pooled results of 15 studies marked with Brdu showed significant effects of acupuncture for improving proliferation when compared with control groups (P < 0.01); 13 studies marked with Nestin showed significant effects of acupuncture for increasing proliferation when compared with control groups (P < 0.01); 4 studies marked with PSA-NCAM showed significant effects of acupuncture for enhancing migration when compared with control groups (P < 0.01); 4 studies marked with NeuN showed significant effects of acupuncture for stimulating differentiation when compared with control groups (P < 0.01). The findings suggest that acupuncture is a prospective therapy targeting neurogenesis for ischemic stroke.

The effects of retinal abnormalities on the multifocal visual evoked potential.

PubMed

Chen, John Y; Hood, Donald C; Odel, Jeffrey G; Behrens, Myles M

2006-10-01

To examine the effects on the amplitude and latency of the multifocal visual evoked potential (mfVEP) in retinal diseases associated with depressed multifocal electroretinograms (mfERG). Static automated perimetry (SAP), mfERGs, and mfVEPs were obtained from 15 individuals seen by neuro-ophthalmologists and diagnosed with retinal disease based on funduscopic examination, visual field, and mfERG. Optic neuropathy was ruled out in all cases. Diagnoses included autoimmune retinopathy (n = 3), branch retinal arterial occlusion (n = 3), branch retinal vein occlusion (n = 1), vitamin A deficiency (n = 1), digoxin/age-related macular degeneration (n = 1), multiple evanescent white dot syndrome (n = 1), and nonspecific retinal disease (n = 5). Patients were selected from a larger group based on abnormal mfERG amplitudes covering a diameter of 20 degrees or greater. Fourteen (93%) of 15 patients showed significant mfVEP delays, as determined by either mean latency or the probability of a cluster of delayed local responses. Thirteen of 15 patients had normal mfVEP amplitudes in regions corresponding to markedly reduced or nonrecordable mfERG responses. These findings can be mimicked in normal individuals by viewing the display through a neutral-density filter. Retinal diseases can result in mfVEPs of relatively normal amplitudes, often with delays, in regions showing decreased mfERG responses and visual field sensitivity loss. Consequently, a retinal problem can be missed, or dismissed as functional, if a diagnosis is based on an mfVEP of normal or near-normal amplitude. Further, in patients with marked mfVEP delays, a retinal problem could be confused with optic neuritis, especially in a patient with a normal appearing fundus.

A Polarization-Dependent Normal Incident Quantum Cascade Detector Enhanced Via Metamaterial Resonators.

PubMed

Wang, Lei; Zhai, Shen-Qiang; Wang, Feng-Jiao; Liu, Jun-Qi; Liu, Shu-Man; Zhuo, Ning; Zhang, Chuan-Jin; Wang, Li-Jun; Liu, Feng-Qi; Wang, Zhan-Guo

2016-12-01

The design, fabrication, and characterization of a polarization-dependent normal incident quantum cascade detector coupled via complementary split-ring metamaterial resonators in the infrared regime are presented. The metamaterial structure is designed through three-dimensional finite-difference time-domain method and fabricated on the top metal contact, which forms a double-metal waveguide together with the metallic ground plane. With normal incidence, significant enhancements of photocurrent response are obtained at the metamaterial resonances compared with the 45° polished edge coupling device. The photocurrent response enhancements exhibit clearly polarization dependence, and the largest response enhancement factor of 165% is gained for the incident light polarized parallel to the split-ring gap.

Immune reactions in acute viral hepatitis.

PubMed Central

Newble, D I; Holmes, K T; Wangel, A G; Forbes, I J

1975-01-01

Serial studies of PHA-induced lymphocyte transformation, serum autoantibodies, immunoglobulins and complement were performed in seventeen patients with hepatitis A and nine patients with hepatitis B. In both types of hepatitis PHA-induced transformation was markedly impaired during the 1st week after the onset of jaundice and there was less marked but prolonged impairment for a further period of 6-10 weeks. A group of eleven subjects with a previous history of hepatitis had values which were similar to those of healthy persons. Serum from patients with hepatitis A and hepatitis B contains an inhibitor of lymphocyte response to PHA. The inhibitor depresses the function of both patients' and normal lymphocytes and is only detectable during the acute phase of the illness. Washing lymphocytes free from autologous serum did not restore the PHA response to normal but the markedly impaired response present during the first 2 weeks of the illness was improved. A serum factor or factors may therefore be responsible for at least part of the impaired response of lymphocytes to PHA during the acute phase of hepatitis but does not appear to account for the more prolonged impairment of the PHA response. The protracted lymphocyte defect is possibly induced by hepatitis virus. The incidence of autoantibodies and the changes in immunoglobulin levels were similar to those reported by other workers. PMID:1204253

Autoimmune hepatitis during intravenous glucocorticoid pulse therapy for Graves' ophthalmopathy treated successfully with glucocorticoids themselves.

PubMed

Marinò, M; Morabito, E; Altea, M A; Ambrogini, E; Oliveri, F; Brunetto, M R; Pollina, L E; Campani, D; Vitti, P; Bartalena, L; Pincheral, A; Marcocci, C

2005-03-01

We report a case of acute hepatitis of autoimmune origin which occurred in a 43-yr-old woman during iv glucocorticoid (GC) pulse therapy for Graves' ophthalmopathy (GO). Prior to therapy, liver function tests were normal with no previous history of liver disorders or conditions predisposing to GC-associated liver damage. After the administration of a 4.7-g cumulative dose of methylprednisolone acetate, there was a marked increase of liver enzymes, prompting immediate discontinuation of iv GC. Nevertheless, liver enzymes increased further, reaching a peak 45 days later, with values 30- to 50-fold greater than those prior to therapy, associated with evidence of impaired liver function. Liver biopsy showed a marked lymphocytic infiltration, likely indicating an autoimmune hepatitis. Based on the assumption that following GC-induced immune suppression, autoimmune hepatitis might have been precipitated by sudden re-activation of the immune system during interpulse periods, we treated the patient with im and then oral GC, in order to re-induce immune suppression. Within three days from re-institution of GC therapy, there was a marked reduction of liver enzymes and amelioration of liver function. Complete normalization was achieved two months later, while the patient was still receiving a low maintenance dose of oral prednisone.

Male chest enhancement: pectoral implants.

PubMed

Benito-Ruiz, J; Raigosa, J M; Manzano-Surroca, M; Salvador, L

2008-01-01

The authors present their experience with the pectoral muscle implant for male chest enhancement in 21 patients. The markings and technique are thoroughly described. The implants used were manufactured and custom made. The candidates for implants comprised three groups: group 1 (18 patients seeking chest enhancement), group 2 (1 patient with muscular atrophy), and group 3 (2 patients with muscular injuries). Because of the satisfying results obtained, including significant enhancement of the chest contour and no major complications, this technique is used for an increasing number of male cosmetic surgeries.

Role of genotype-based approach in the clinical management of adult acute myeloid leukemia with normal cytogenetics.

PubMed

Cagnetta, Antonia; Adamia, Sophia; Acharya, Chirag; Patrone, Franco; Miglino, Maurizio; Nencioni, Alessio; Gobbi, Marco; Cea, Michele

2014-06-01

Acute myeloid leukemia (AML) is the most common form of acute leukemia affecting adults. Although it is a complex disease driven by numerous genetic and epigenetic abnormalities, nearly 50% of patients exhibit a normal karyotype (CN-AML) with an intermediate cytogenetic risk. However, a widespread genomic analysis has recently shown the recurrence of genomic aberrations in this category (mutations of FLT3, CEBPA, NPM1, RUNX1, TET2, IDH1/2, DNMT3A, ASXL1, MLL and WT1) thus revealing its marked genomic heterogeneity. In this perspective, a global gene expression analysis of AML patients provides an independent prognostic marker to categorize each patient into clinic-pathologic subgroups based on its molecular genetic defects. Consistently such classification, taking into account the uniqueness of each AML patient, furnishes an individualized treatment approach leading a step closer to personalized medicine. Overall the genome-wide analysis of AML patients, by providing novel insights into biology of this tumor, furnishes accurate prognostic markers as well as useful tools for selecting the most appropriate treatment option. Moreover it provides novel therapeutic targets useful to enhance efficacy of the current anti-AML therapeutics. Here we describe the prognostic relevance of such new genetic data and discuss how this approach can be used to improve survival and treatment of AML patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

More normal than not: a qualitative assessment of the developmental experiences of gay male youth.

PubMed

Eccles, Thomas A; Sayegh, M A; Fortenberry, J D; Zimet, G D

2004-11-01

To examine gay youth experiences within the context of normal adolescent development. Thematic analyses of interviews with 13 self-identified gay male youth, aged 16-22 years, each reporting minimal sexual identity distress, were completed. Interviews focused on: (a) descriptions of developmental changes perceived to occur for all adolescents, (b) descriptions of the participants' developmental experience, and (c) participants' direct comparisons of their perceptions of gay and nongay developmental experience. Data were analyzed by two investigators who, after initial review of the interview transcripts, developed a unified coding template to permit systematic analysis of the transcripts for recurrent themes. (a) Few (2 of 13) participants reported overall developmental experience markedly different from nongay peers. (b) Peer interaction was seen as the domain most different from that of nongay peers. (c) Open gay self-identification altered, generally positively, all peer interaction. (d) Increased peer interaction enhanced maturity in other domains. (e) Family dynamics were not substantively altered by open gay self-identification. (f) Middle and high school were identified as relatively hostile environments in which to openly identify as gay, affecting the timing and the extent of self-disclosure. (g) Developmental progress showed asynchrony across developmental domains. General developmental dysfunction is not inevitable for gay adolescents, nor is identifiable personal or family pathology directly related to sexual identity.

Integrity of normal-appearing white matter: Influence of age, visible lesion burden and hypertension in patients with small-vessel disease.

PubMed

Muñoz Maniega, Susana; Chappell, Francesca M; Valdés Hernández, Maria C; Armitage, Paul A; Makin, Stephen D; Heye, Anna K; Thrippleton, Michael J; Sakka, Eleni; Shuler, Kirsten; Dennis, Martin S; Wardlaw, Joanna M

2017-02-01

White matter hyperintensities accumulate with age and occur in patients with stroke, but their pathogenesis is poorly understood. We measured multiple magnetic resonance imaging biomarkers of tissue integrity in normal-appearing white matter and white matter hyperintensities in patients with mild stroke, to improve understanding of white matter hyperintensities origins. We classified white matter into white matter hyperintensities and normal-appearing white matter and measured fractional anisotropy, mean diffusivity, water content (T1-relaxation time) and blood-brain barrier leakage (signal enhancement slope from dynamic contrast-enhanced magnetic resonance imaging). We studied the effects of age, white matter hyperintensities burden (Fazekas score) and vascular risk factors on each biomarker, in normal-appearing white matter and white matter hyperintensities, and performed receiver-operator characteristic curve analysis. Amongst 204 patients (34.3-90.9 years), all biomarkers differed between normal-appearing white matter and white matter hyperintensities ( P < 0.001). In normal-appearing white matter and white matter hyperintensities, mean diffusivity and T1 increased with age ( P < 0.001), all biomarkers varied with white matter hyperintensities burden ( P < 0.001; P = 0.02 signal enhancement slope), but only signal enhancement slope increased with hypertension ( P = 0.028). Fractional anisotropy showed complex age-white matter hyperintensities-tissue interactions; enhancement slope showed white matter hyperintensities-tissue interactions. Mean diffusivity distinguished white matter hyperintensities from normal-appearing white matter best at all ages. Blood-brain barrier leakage increases with hypertension and white matter hyperintensities burden at all ages in normal-appearing white matter and white matter hyperintensities, whereas water mobility and content increase as tissue damage accrues, suggesting that blood-brain barrier leakage mediates small vessel disease-related brain damage.

Enhancement of RNA from Formalin-Fixed Paraffin-Embedded (FFPE) Samples

EPA Science Inventory

Enhancement of RNA from Formalin-Fixed Paraffin-Embedded (FFPE) Samples Susan Hester1, Leah Wehmas1, Carole Yauk2, Marc Roy3, Mark M. Gosink3, Deidre D. Wilk4, Thomas Hill III5, Charles E. Wood11Office of Research and Development, US EPA, RTP, NC 27709, USA, 2Environmental Health...

Internal Quality Assurance--Enhancing Quality Culture. ENQA Workshop Report 16

ERIC Educational Resources Information Center

ENQA (European Association for Quality Assurance in Higher Education), 2010

2010-01-01

The European Association for Quality Assurance in Higher Education (ENQA), in cooperation with the Quality Assurance Agency (QAA, UK), organised a seminar on theme "Internal Quality Assurance--Enhancing quality culture" which was held on 8-9 June, 2010 in London, United Kingdom. The seminar marked the fourth annual meeting of the ENQA…

Robust nanogenerators based on graft copolymers via control of dielectrics for remarkable output power enhancement

PubMed Central

Lee, Jae Won; Cho, Hye Jin; Chun, Jinsung; Kim, Kyeong Nam; Kim, Seongsu; Ahn, Chang Won; Kim, Ill Won; Kim, Ju-Young; Kim, Sang-Woo; Yang, Changduk; Baik, Jeong Min

2017-01-01

A robust nanogenerator based on poly(tert-butyl acrylate) (PtBA)–grafted polyvinylidene difluoride (PVDF) copolymers via dielectric constant control through an atom-transfer radical polymerization technique, which can markedly increase the output power, is demonstrated. The copolymer is mainly composed of α phases with enhanced dipole moments due to the π-bonding and polar characteristics of the ester functional groups in the PtBA, resulting in the increase of dielectric constant values by approximately twice, supported by Kelvin probe force microscopy measurements. This increase in the dielectric constant significantly increased the density of the charges that can be accumulated on the copolymer during physical contact. The nanogenerator generates output signals of 105 V and 25 μA/cm2, a 20-fold enhancement in output power, compared to pristine PVDF–based nanogenerator after tuning the surface potential using a poling method. The markedly enhanced output performance is quite stable and reliable in harsh mechanical environments due to the high flexibility of the films. On the basis of these results, a much faster charging characteristic is demonstrated in this study. PMID:28560339

A class of circadian long non-coding RNAs mark enhancers modulating long-range circadian gene regulation

PubMed Central

Fan, Zenghua; Zhao, Meng; Joshi, Parth D.; Li, Ping; Zhang, Yan; Guo, Weimin; Xu, Yichi; Wang, Haifang; Zhao, Zhihu

2017-01-01

Abstract Circadian rhythm exerts its influence on animal physiology and behavior by regulating gene expression at various levels. Here we systematically explored circadian long non-coding RNAs (lncRNAs) in mouse liver and examined their circadian regulation. We found that a significant proportion of circadian lncRNAs are expressed at enhancer regions, mostly bound by two key circadian transcription factors, BMAL1 and REV-ERBα. These circadian lncRNAs showed similar circadian phases with their nearby genes. The extent of their nuclear localization is higher than protein coding genes but less than enhancer RNAs. The association between enhancer and circadian lncRNAs is also observed in tissues other than liver. Comparative analysis between mouse and rat circadian liver transcriptomes showed that circadian transcription at lncRNA loci tends to be conserved despite of low sequence conservation of lncRNAs. One such circadian lncRNA termed lnc-Crot led us to identify a super-enhancer region interacting with a cluster of genes involved in circadian regulation of metabolism through long-range interactions. Further experiments showed that lnc-Crot locus has enhancer function independent of lnc-Crot's transcription. Our results suggest that the enhancer-associated circadian lncRNAs mark the genomic loci modulating long-range circadian gene regulation and shed new lights on the evolutionary origin of lncRNAs. PMID:28335007

On denture marking.

PubMed

Borrman, H I; DiZinno, J A; Wasén, J; René, N

1999-06-01

During the last decades in Sweden dentures have been permanently marked with a stainless steel metal band incorporated into the acrylic and containing the patient's birth date, a special number, and "S" for Sweden. The last recommendation issued by the National Board of Health and Welfare states that "the patients shall always be offered denture marking and be informed about the benefit thereof. Denture marking is not permitted if the patient refuses it". Requirements for denture markers have been that they should be biologically inert (when incorporated into the denture), not be expensive, be easy to inscribe, be possible to retrieve after an accident, and survive elevated temperatures for a reasonable time under normal circumstances. Although the frequency of edentulousness has decreased in recent years due to the improvement in oral health there remains a need to address the issue of marking of complete dentures, because there is a large variation in the oral status of populations in different countries. Given that only one marked denture can reveal the identity of a deceased person when all other methods fail to do so, makes it worthwhile. Furthermore, denture marking is important in long-term care facilities. We have investigated the issue of denture marking in Europe and in the United States. The results from the European survey show that denture marking is, to our knowledge regulated by law only in Sweden and Iceland. In the US denture marking is so far mandatory in 21 states while New York State requires dentures to be marked if the patient requests it and several other states impose the obligation to mark dentures on long-term care facilities. Since there is no international consensus regarding the issue of denture marking it is important to address it. A survey from the Nordic countries has shown that if denture marking was in general use, the contribution to the establishment of identity by forensic odontology in cases of fire would increase by about 10%. This means that about 25 more individuals could have been identified if their dentures were marked. Increased international collaboration is needed to solve the issue of denture marking for clinical and forensic purposes.

Transmissible Gastroenteritis in Feeder Pigs: Observations on the Jejunal Epithelium of Normal Feeder Pigs and Feeder Pigs Infected with TGE Virus

PubMed Central

Morin, M.; Morehouse, L. G.

1974-01-01

Light and electron microscopy findings in the jejunal mucosa of the normal feeder pig and feeder pigs infected with transmissible gastroenteritis (TGE) virus are reported. Villi in the mid jejunum of the normal feeder pig were elongated, finger shaped and covered with a layer of columnar absorptive cells with a well developed and regular brush border. Severe lesions of villous atrophy were present in all jejunal segments of feeder swine killed 96 hours post infection with TGE virus. Atrophic villi were covered by flat to cuboidal cells with a poorly developed brush border in some areas. In other segments, cells varied in appearance from sub-columnar to columnar type of near normal appearance. The ultrastructure of the jejunal absorptive cells in the normal feeder pig was found to be similar to that described for the jejunal cells of other adult mammals. There were no significant indications of high pinocytotic activity. The epithelial cells covering the atrophic villi of TGE infected pigs had a fine structure similar to that described for the crypt cells, ranging in appearance from very immature to moderately differentiated cells. Microvilli were very short, decreased markedly in number and irregular in arrangement. The terminal web was poorly developed. Strands of rough endoplasmic reticulum were markedly diminished and an increase in free ribosomes was noted. The significance of these observations in explaining pathogenesis of TGE in feeder pigs is discussed. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6.Fig. 7.Fig. 8. PMID:4277743

Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon.

PubMed

Yang, K; Lamprecht, S A; Liu, Y; Shinozaki, H; Fan, K; Leung, D; Newmark, H; Steele, V E; Kelloff, G J; Lipkin, M

2000-09-01

In this study we investigated the chemopreventive effects of quercetin and rutin when added to standard AIN-76A diet and fed to normal and azoxymethane (AOM)-treated mice. Early changes in colonic mucosa were analyzed, including colonic cell proliferation, apoptotic cell death, cyclin D(1) expression and focal areas of dysplasia (FAD). The findings show that the number of colonic epithelial cells per crypt column increased (P: < 0.01) in each normal mouse group fed the flavonoids; AOM administration increased colonic crypt cell proliferation and resulted in a marked rise of bromodeoxyuridine-labeled cells in the lower proliferative zone of the crypt. Both supplementary dietary quercetin and rutin increased the apoptotic index and caused a redistribution of apoptotic cells along the crypt axis in normal mice fed a standard AIN-76A diet. The number of apoptotic cells/column and apoptotic indices markedly increased (P: < 0.01) in the AOM-treated group compared with untreated animals; apoptotic cells expanded throughout the colonic crypts after flavonoid supplementation and AOM administration. Positive cyclin D(1) expression was detected in mice on diets supplemented either with quercetin (P: < 0.01) or rutin (P: < 0.05). AOM administration resulted in the formation of FAD. Both the number of mice exhibiting FAD and the total numer of FAD observed were significantly reduced (P: < 0.01) in AOM-treated animals fed flavonoids compared with mice maintained on the standard AIN-76A diet. Surprisingly, however, quercetin alone was able to induce FAD in 22% of normal mice fed the standard AIN-76A diet.

Dynamic contrast-enhanced x-ray CT measurement of cerebral blood volume in a rabbit tumor model

NASA Astrophysics Data System (ADS)

Cenic, Aleksa; Lee, Ting-Yim; Craen, Rosemary A.; Gelb, Adrian W.

1998-07-01

Cerebral blood volume (CBV) is a major determinant of intracranial pressure (ICP). Hyperventilation is commonly employed to reduce raised ICP (e.g. in brain tumour patients) presumably through its effect on CBV. With the advent of slip- ring CT scanners, dynamic contrast-enhanced imaging allows for the measurement of CBV with high spatial resolution. Using a two-compartment model to characterize the distribution of X- ray contrast agent in the brain, we have developed a non- equilibrium CT method to measure CBV in normal and pathological regions. We used our method to investigate the effect of hyperventilation on CBV during propofol anaesthesia in rabbits with implanted brain tumours. Eight New Zealand White rabbits with implanted VX2 carcinoma brain tumours were studied. For each rabbit, regional CBV measurements were initially made at normocapnia (PaCO2 40 mmHg) and then at hyperventilation (PaCO2 25 mmHg) during propofol anaesthesia. The head was positioned such that a coronal image through the brain incorporated a significant cross-section of the brain tumour as well as a radial artery in a forelimb. Images at the rate of 1 per second were acquired for 2 minutes as Omnipaque 300 (1.5 ml/kg rabbit weight) was injected via a peripheral vein. In these CT images, regions of interest in the brain tissue (e.g. tumour, contra-lateral normal, and peri-tumoural) and the radial artery were drawn. For each region, the mean CT number in pre-contrast images was subtracted from the mean CT number in post-contrast images to produce either the tissue contrast concentration curve, or the arterial contrast concentration curve. Using our non- equilibrium analysis method based on a two-compartment model, regional CBV values were determined from the measured contrast concentration curves. From our study, the mean CBV values [+/- SD] in the tumour, peri-tumoural, and contra-lateral normal regions during normocapnia were: 5.47 plus or minus 1.97, 3.28 plus or minus 1.01, and 1.86 plus or minus 0.54 ml/100 g, respectively. Following hyperventilation, we found a significant decrease (p less than 0.025) of 10.4% in CBV in the peri-tumoural region, and no statistically significant change in CBV in the tumour or contra-lateral normal regions. We have developed a convenient method for measuring CBV in normal and pathological tissue using a slip-ring CT scanner. In a brain tumour model, we found that CBV was markedly increased in tumour and peri-tumoural regions compared to normal regions. Our results suggest that the reduction of raised ICP following hyperventilation during propofol anaesthesia may be mainly due to a reduction in CBV in the peri-tumoural tissue rather than in the bulk of the tumour or normal regions. Our method has the potential to provide further knowledge on the cerebral hemodynamics of space- occupying lesions during different anaesthetic interventions or treatment regiments.

Surface laser marking optimization using an experimental design approach

NASA Astrophysics Data System (ADS)

Brihmat-Hamadi, F.; Amara, E. H.; Lavisse, L.; Jouvard, J. M.; Cicala, E.; Kellou, H.

2017-04-01

Laser surface marking is performed on a titanium substrate using a pulsed frequency doubled Nd:YAG laser ( λ= 532 nm, τ pulse=5 ns) to process the substrate surface under normal atmospheric conditions. The aim of the work is to investigate, following experimental and statistical approaches, the correlation between the process parameters and the response variables (output), using a Design of Experiment method (DOE): Taguchi methodology and a response surface methodology (RSM). A design is first created using MINTAB program, and then the laser marking process is performed according to the planned design. The response variables; surface roughness and surface reflectance were measured for each sample, and incorporated into the design matrix. The results are then analyzed and the RSM model is developed and verified for predicting the process output for the given set of process parameters values. The analysis shows that the laser beam scanning speed is the most influential operating factor followed by the laser pumping intensity during marking, while the other factors show complex influences on the objective functions.

H2O2 mediates ALA-induced glutathione and ascorbate accumulation in the perception and resistance to oxidative stress in Solanum lycopersicum at low temperatures.

PubMed

Liu, Tao; Hu, Xiaohui; Zhang, Jiao; Zhang, Junheng; Du, Qingjie; Li, Jianming

2018-02-15

Low temperature is a crucial factor influencing plant growth and development. The chlorophyll precursor, 5-aminolevulinic acid (ALA) is widely used to improve plant cold tolerance. However, the interaction between H 2 O 2 and cellular redox signaling involved in ALA-induced resistance to low temperature stress in plants remains largely unknown. Here, the roles of ALA in perceiving and regulating low temperature-induced oxidative stress in tomato plants, together with the roles of H 2 O 2 and cellular redox states, were characterized. Low concentrations (10-25 mg·L - 1 ) of ALA enhanced low temperature-induced oxidative stress tolerance of tomato seedlings. The most effective concentration was 25 mg·L - 1 , which markedly increased the ratio of reduced glutathione and ascorbate (GSH and AsA), and enhanced the activities of superoxide dismutase, catalase, ascorbate peroxidase, dehydroascorbate reductase, and glutathione reductase. Furthermore, gene expression of respiratory burst oxidase homolog1 and H 2 O 2 content were upregulated with ALA treatment under normal conditions. Treatment with exogenous H 2 O 2 , GSH, and AsA also induced plant tolerance to oxidative stress at low temperatures, while inhibition of GSH and AsA syntheses significantly decreased H 2 O 2 -induced oxidative stress tolerance. Meanwhile, scavenging or inhibition of H 2 O 2 production weakened, but did not eliminate, GSH- or AsA- induced tomato plant tolerance to oxidative stress at low temperatures. Appropriate concentrations of ALA alleviated the low temperature-induced oxidative stress in tomato plants via an antioxidant system. The most effective concentration was 25 mg·L - 1 . The results showed that H 2 O 2 induced by exogenous ALA under normal conditions is crucial and may be the initial step for perception and signaling transmission, which then improves the ratio of GSH and AsA. GSH and AsA may then interact with H 2 O 2 signaling, resulting in enhanced antioxidant capacity in tomato plants at low temperatures.

Defective neutrophil chemotaxis in juvenile periodontitis.

PubMed Central

Clark, R A; Page, R C; Wilde, G

1977-01-01

Neutrophil chemotaxis was evaluated in nine patients with juvenile periodontitis, with normal subjects and patients with the adult form of periodontitis as controls. Defective chemotactic responses were observed in neutrophils from seven of nine juvenile patients, and a reduced level of complement-derived chemotactic activity was demonstrated in serum from four patients. These determinations were normal in all the patients with adult periodontitis. Serum from five of the juvenile patients contained a heat-stable, non-dialyzable factor that markedly inhibited the chemotaxis of normal neutrophils. Thus the characteristic tissue destruction seen in juvenile periodontitis may be, at least in part, a consequence of a failure of host defense mechanisms. PMID:591063

Statistical methods for the forensic analysis of striated tool marks

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

Hoeksema, Amy Beth

In forensics, fingerprints can be used to uniquely identify suspects in a crime. Similarly, a tool mark left at a crime scene can be used to identify the tool that was used. However, the current practice of identifying matching tool marks involves visual inspection of marks by forensic experts which can be a very subjective process. As a result, declared matches are often successfully challenged in court, so law enforcement agencies are particularly interested in encouraging research in more objective approaches. Our analysis is based on comparisons of profilometry data, essentially depth contours of a tool mark surface taken alongmore » a linear path. In current practice, for stronger support of a match or non-match, multiple marks are made in the lab under the same conditions by the suspect tool. We propose the use of a likelihood ratio test to analyze the difference between a sample of comparisons of lab tool marks to a field tool mark, against a sample of comparisons of two lab tool marks. Chumbley et al. (2010) point out that the angle of incidence between the tool and the marked surface can have a substantial impact on the tool mark and on the effectiveness of both manual and algorithmic matching procedures. To better address this problem, we describe how the analysis can be enhanced to model the effect of tool angle and allow for angle estimation for a tool mark left at a crime scene. With sufficient development, such methods may lead to more defensible forensic analyses.« less

A quantitative trait locus mixture model that avoids spurious LOD score peaks.

PubMed Central

Feenstra, Bjarke; Skovgaard, Ib M

2004-01-01

In standard interval mapping of quantitative trait loci (QTL), the QTL effect is described by a normal mixture model. At any given location in the genome, the evidence of a putative QTL is measured by the likelihood ratio of the mixture model compared to a single normal distribution (the LOD score). This approach can occasionally produce spurious LOD score peaks in regions of low genotype information (e.g., widely spaced markers), especially if the phenotype distribution deviates markedly from a normal distribution. Such peaks are not indicative of a QTL effect; rather, they are caused by the fact that a mixture of normals always produces a better fit than a single normal distribution. In this study, a mixture model for QTL mapping that avoids the problems of such spurious LOD score peaks is presented. PMID:15238544

A quantitative trait locus mixture model that avoids spurious LOD score peaks.

PubMed

Feenstra, Bjarke; Skovgaard, Ib M

2004-06-01

In standard interval mapping of quantitative trait loci (QTL), the QTL effect is described by a normal mixture model. At any given location in the genome, the evidence of a putative QTL is measured by the likelihood ratio of the mixture model compared to a single normal distribution (the LOD score). This approach can occasionally produce spurious LOD score peaks in regions of low genotype information (e.g., widely spaced markers), especially if the phenotype distribution deviates markedly from a normal distribution. Such peaks are not indicative of a QTL effect; rather, they are caused by the fact that a mixture of normals always produces a better fit than a single normal distribution. In this study, a mixture model for QTL mapping that avoids the problems of such spurious LOD score peaks is presented.

Sociocultural-Geospatial Anthropological Portal (SC-GAP): Enhancing Sociocultural Understanding Through Crowdsourced Service Member Narratives

DTIC Science & Technology

2015-06-01

sociocultural understanding of the operating environment. Mark Herbert provides a snap shot of the current frustration with this DOD shortcoming stating, “we...41 Mark Herbert , “The Human Domain: The Army’s Necessary Push toward Squishiness,” Military Review (Sept–Oct...Theory,” 20. 77 Derived from the following works: Department of the Army, Insurgencies and Countering Insurgencies (FM 3-24), 3-4; Helen Spencer

Protecting the turf: The effect of territorial marking on others' creativity.

PubMed

Brown, Graham; Baer, Markus

2015-11-01

Territorial marking allows people to communicate that a territory has been claimed. Across 2 studies, we examine the impact of territorial marking of one's ideas on others' invited creativity when asked to provide feedback. Integrating research on territoriality and self-construal, we examine the effect of control-oriented marking on invited creativity (Study 1), and the extent to which an independent versus interdependent self-construal moderates this effect (Study 2). Results of Study 1 demonstrate that the use of control-oriented marking to communicate a territorial claim over one's ideas inhibits invited creativity, and this effect is mediated by intrinsic motivation. Also consistent with our hypotheses, the results of Study 2 show that self-construal moderates the effect of control-oriented marking on others' intrinsic motivation and creativity. Marking diminishes invited creativity among people with an independent self-construal but serves to enhance the creativity of those with an interdependent self-construal. Consistent with Study 1, intrinsic motivation mediates this moderated effect. Our results highlight the important but heretofore understudied role of territoriality in affecting others' creativity as well as the role of independent versus interdependent self-construal in shaping this effect. (c) 2015 APA, all rights reserved).

The relevance of mineralization lag time in the evaluation of histologic changes in renal osteodystrophy.

PubMed

Libbey, N P; Chazan, J A; London, M R; Pono, L; Abuelo, J G

1993-04-01

We examined bone biopsies from 47 patients on chronic hemodialysis, and analyzed the histomorphometric and biochemical findings and histologic quantitation of bone aluminium, looking primarily at mineralization lag time (Mlt) to evaluate its usefulness in categorization of renal osteodystrophy (ROD). The patients were categorized as having either relatively normal Mlt (< 35 days, n = 21 patients), moderately prolonged Mlt (35-100 days, n = 13 patients) or markedly prolonged Mlt (> 100 days, n = 13 patients). The group with relatively normal Mlt showed significantly higher C-terminal parathyroid hormone (PTHc) levels (26,141 +/- 19,270 vs 7,226 +/- 6,073 and 4,434 +/- 4,000 pg/ml) than the moderately or markedly prolonged Mlt groups (p < .01) and was associated with histologic characteristics of osteitis fibrosa or mild hyperparathyroidism (BFR/BS range 0.146-0.947 mcm3/mcm2/d). The group with markedly prolonged Mlt included one patient with classic and 11 with adynamic osteomalacia (BFR/BS range 0.009-0.099) and had greater bone aluminum (Al.S/OS 35.3 +/- 26.7% vs 7.2 +/- 9.0%) than the normal Mlt group (p < .01). The group with moderately prolonged Mlt included two patients with aplastic bone disease (Mlt 80.0 and 84.6 days, and Al.S/OS 100.0 and 72.3%) and 11 patients with features of hyperparathyroidism and osteomalacia (BFR/BS range 0.068-0.243) with variable but generally intermediate bone aluminum deposition (Al.S/OS 22.5 +/- 19.9%). Like BFR/BS and other dynamic parameters Mlt correlates with morphologic types of ROD which primarily reflect bone turnover, but it may also suggest varying degrees of mineralization impairment in a spectrum ranging from high to low turnover types of ROD. Its usefulness in this respect should not be overlooked.

Pericortical Enhancement on Delayed Postgadolinium Fluid-Attenuated Inversion Recovery Images in Normal Aging, Mild Cognitive Impairment, and Alzheimer Disease.

PubMed

Freeze, W M; Schnerr, R S; Palm, W M; Jansen, J F; Jacobs, H I; Hoff, E I; Verhey, F R; Backes, W H

2017-09-01

Breakdown of BBB integrity occurs in dementia and may lead to neurodegeneration and cognitive decline. We assessed whether extravasation of gadolinium chelate could be visualized on delayed postcontrast FLAIR images in older individuals with and without cognitive impairment. Seventy-four individuals participated in this study (15 with Alzheimer disease, 33 with mild cognitive impairment, and 26 with normal cognition). We assessed the appearance of pericortical enhancement after contrast administration, MR imaging markers of cerebrovascular damage, and medial temporal lobe atrophy. Three participants who were positive for pericortical enhancement (1 with normal cognition and 2 with mild cognitive impairment) were followed up for approximately 2 years. In vitro experiments with a range of gadolinium concentrations served to elucidate the mechanisms underlying the postcontrast FLAIR signals. Postcontrast pericortical enhancement was observed in 21 participants (28%), including 6 individuals with Alzheimer disease (40%), 10 with mild cognitive impairment (30%), and 5 with normal cognition (19%). Pericortical enhancement was positively associated with age ( P < .02) and ischemic stroke ( P < .05), but not with cognitive status ( P = .3). Foci with enhanced signal remained stable across time in all follow-up cases. The in vitro measurements confirmed that FLAIR imaging is highly sensitive for the detection of low gadolinium concentrations in CSF, but not in cerebral tissue. Postcontrast pericortical enhancement on FLAIR images occurs in older individuals with normal cognition, mild cognitive impairment, and dementia. It may represent chronic focal superficial BBB leakage. Future longitudinal studies are needed to determine its clinical significance. © 2017 by American Journal of Neuroradiology.

Handheld lasers allow efficient detection of fluorescent marked organisms in the field.

PubMed

Rice, Kevin B; Fleischer, Shelby J; De Moraes, Consuelo M; Mescher, Mark C; Tooker, John F; Gish, Moshe

2015-01-01

Marking organisms with fluorescent dyes and powders is a common technique used in ecological field studies that monitor movement of organisms to examine life history traits, behaviors, and population dynamics. External fluorescent marking is relatively inexpensive and can be readily employed to quickly mark large numbers of individuals; however, the ability to detect marked organisms in the field at night has been hampered by the limited detection distances provided by portable fluorescent ultraviolet lamps. In recent years, significant advances in LED lamp and laser technology have led to development of powerful, low-cost ultraviolet light sources. In this study, we evaluate the potential of these new technologies to improve detection of fluorescent-marked organisms in the field and to create new possibilities for tracking marked organisms in visually challenging environments such as tree canopies and aquatic habitats. Using handheld lasers, we document a method that provides a fivefold increase in detection distance over previously available technologies. This method allows easy scouting of tree canopies (from the ground), as well as shallow aquatic systems. This novel detection method for fluorescent-marked organisms thus promises to significantly enhance the use of fluorescent marking as a non-destructive technique for tracking organisms in natural environments, facilitating field studies that aim to document otherwise inaccessible aspects of the movement, behavior, and population dynamics of study organisms, including species with significant economic impacts or relevance for ecology and human health.

Evaluation of a fluorescence feedback system for guidance of laser angioplasty.

PubMed

Deckelbaum, L I; Desai, S P; Kim, C; Scott, J J

1995-01-01

Laser-induced fluorescence spectroscopy (LIFS) may be capable of guiding laser angioplasty by discriminating normal and atherosclerotic artery and by determining catheter-tissue environment. Previous optical multichannel analyzer based LIFS systems have been expensive and cumbersome. To simplify LIFS, a system based on photomultiplier tubes was developed and evaluated. Tissue fluorescence was induced by a helium cadmium laser (wavelength = 325 nm, power = 0.2-0.5 mW), collected by clinical multifiber laser angioplasty catheters and directed through one of two filters (10 nm bandpass, 380 nm or 440 nm peak transmission) to a photomultiplier tube. An LIFS ratio was defined as the relative intensity at 380:440 nm after calibration with an elastin fluorescence spectrum; 157 coronary artery cadaveric specimens were evaluated spectroscopically and histologically. To evaluate the utility of LIFS to optimize catheter position by determining catheter-tissue contact, by determining saline dilution of blood, and by orienting eccentric multifiber catheters a new variable, the total fluorescence intensity (TFI) was defined as the sum of arterial fluorescence intensities at 380 nm and 440 nm. TFI was recorded in vitro through multifiber catheters from 20 arterial specimens in vitro in blood and evaluated as a function of the catheter-to-tissue distance (d) over a range from 0 to 400 mu. Defining normal specimens as those with an intimal thickness < or = 200 mu, and atherosclerotic as those with an intimal thickness > 200 mu, 47/50 (94%) normal and 85/107 (79%) atherosclerotic specimens were correctly classified using a threshold LIFS ratio of 2.0. Mean (+/- SE) normal ratio was 1.76 +/- 0.02 and mean atherosclerotic ratio was 2.78 +/- 0.08 (P < or = 0.01). The classification accuracy of atherosclerotic specimens increased with intimal thickness so that 95% of atherosclerotic specimens (69/73) with intimal thickness > or = 400 mu were correctly classified. TFI was capable of determining catheter-tissue contact as maximal TFI was recorded with the catheter in contact with the tissue (d = 0 mu) and decreased markedly with distance (to 52 +/- 6% at d = 100 mu, 19 +/- 4% at d = 200 mu, and 3 +/- 1% at d = 300 mu). TFI was recorded from ten arterial specimens in blood/saline mixtures ranging in hematocrit from 0% (saline) to 50% (whole blood). TFI was capable of detecting saline hemodilution of blood as TFI decreased markedly at higher hematocrits such that TFI could only by recorded at hematocrits < 10% for catheter-to-tissue distances > or = 300 mu. TFI was recorded through ecentric multifiber catheters from 25 arterial specimens and eval-uated as a function of the degree of catheter-tissue overlap. TFI was capable of detecting maximal catheter-tissue overlap as TFI correlated linearly with the area (A) of overlap (TFI = 1.12 A + .07, r = 0.92). By discriminating atherosclerotic from normal tissue and by confirming catheter-tissue contact and saline hemodilution, fluorescence feedback should minimize irradiation of normal tissue and/or blood and enhance the safety and efficacy of laser angioplasty.

Electrofishing mark-recapture and depletion methodologies evoke behavioral and physiological changes in cutthroat trout

USGS Publications Warehouse

Mesa, M. G.; Schreck, C.B.

1989-01-01

We examined the behavioral and physiological responses of wild and hatchery-reared cutthroat trout Oncorhynchus clarki subjected to a single electroshock, electroshock plus marking, and multiple electroshocks in natural and artificial streams. In a natural stream, cutthroat trout released after capture by electrofishing and marking showed distinct behavioral changes: fish immediately sought cover, remained relatively inactive, did not feed, and were easily approached by a diver. An average of 3–4 h was required for 50% of the fish to return to a seemingly normal mode of behavior, although responses varied widely among collection sites. Using the depletion method, we observed little change in normal behavior offish remaining in the stream section (i.e., uncaptured fish) after successive passes with electrofishing gear. In an artificial stream, hatchery-reared and wild cutthroat trout immediately decreased their rates of feeding and aggression after they were electroshocked and marked. Hatchery fish generally recovered in 2–3 h; wild fish required at least 24 h to recover. Analysis of feeding and aggression data by hierarchical rank revealed no distinct recovery trends among hatchery fish of different ranks; among wild cutthroat trout, however, socially dominant fish seemed to recover faster than intermediate and subordinate fish. Physiological indicators of stress (plasma cortisol and blood lactic acid) increased significantly in cutthroat trout subjected to electroshock plus marking or single or multiple electroshocks. As judged by the magnitude of the greatest change in cortisol and lactate, multiple electroshocks elicited the most severe stress response; however, plasma concentrations of both substances had returned to unstressed control levels by 6 h after treatment. It was evident that electrofishing and the procedures involved with estimating fish population size elicited a general stress response that was manifested not only physiologically but also behaviorally. These responses may affect the accuracy of population size estimates by violating key assumptions of the methods, especially the assumption of equal catchability offish.

Tools, Techniques, and Applications: Normalizing the VR Paradigm

NASA Technical Reports Server (NTRS)

Duncan, Gaeme

2008-01-01

Oshynee's precision Learning Objective performance factor rubrics with associated behavioral anchors integrates with Thinking Worlds(TradeMark), to provide event data recording and dynamic prescriptive feedback. Thinking Worlds(TradeMark) provides SCORM parametric data for reporting within the game and within overarching curricula or workplace evaluation strategy. - Open-sourced, browser-based digital dashboard reporting tools collect data from TW, LMS, LCMS, HR, and workplace metrics or control systems The games may be delivered across the internet or in a range of networked and stand-alone methods using the delivery model (s) required by the host organization.

Analysis of expression of FLI1 and MMP1 in American cutaneous leishmaniasis caused by Leishmania braziliensis infection

PubMed Central

Almeida, Lucas; Silva, Juliana A.; Andrade, Viviane M.; Machado, Paulo; Jamieson, Sarra E.; Carvalho, Edgar M.

2017-01-01

FLI1 (Friend leukemia virus integration 1) and IL6 (interleukin 6; IL-6) are associated with Leishmania braziliensis susceptibility. Cutaneous lesions show exaggerated matrix metalloproteinase 1 (MMP1). In other skin diseases, FLI1 promoter methylation reduces FLI1 expression, and low FLI1 down-regulates MMP1. IL-6 increases FLI1 expression. We hypothesized that epigenetic regulation of FLI1 in cutaneous leishmaniasis, together with IL-6, might determine MMP1 expression. While generally low (<10%), percent FLI1 promoter methylation was lower (P=0.001) in lesion biopsies than normal skin. Contrary to expectation, a strong positive correlation occurred between FLI1 methylation and gene expression in lesions (r=0.98, P=0.0005) and in IL-6-treated L. braziliensis-infected macrophages (r=0.99, P=0.0004). In silico analysis of the FLI1 promoter revealed co-occurring active H3K27ac and repressive DNA methylation marks to enhance gene expression. FLI1 expression was enhanced between 3 and 24 hours post infection in untreated (P=0.0002) and IL-6-treated (P=0.028) macrophages. MMP1 was enhanced in lesion biopsies (P=0.0002), induced (P=0.007) in infected macrophages, but strongly inhibited by IL-6. No correlations occurred between FLI1 and MMP1 expression in lesions or infected macrophages (with/without IL-6). We conclude that MMP1 is regulated by factors other than FLI1, and that the influence of IL-6 on MMP1 was independent of its effect on FLI1. PMID:28119029

Enhanced Antitumorigenic Effects in Glioblastoma on Double Targeting of Pleiotrophin and Its Receptor ALK1

PubMed Central

Grzelinski, Marius; Steinberg, Florian; Martens, Tobias; Czubayko, Frank; Lamszus, Katrin; Aigner, Achim

2009-01-01

In adults, glioblastomas are the most lethal and most frequent malignant brain tumors, and the poor prognosis despite aggressive treatment indicates the need to establish novel targets for molecular intervention. The secreted growth factor pleiotrophin (PTN, HB-GAM, HBNF, OSF-1) shows mitogenic, chemotactic, and transforming activity. Whereas PTN expression is tightly regulated during embryogenesis and is very limited in normal adult tissues, a marked PTN up-regulation is seen in tumors including glioblastomas. Likewise, the PTN receptor anaplastic lymphoma kinase (ALK) has been shown previously to be upregulated and functionally relevant in glioblastoma. In this study, we explore the antitumorigenic effects of the simultaneous ribozyme-mediated knockdown of both receptor and ligand. Various glioblastoma cell lines are analyzed for PTN and ALK expression. Beyond the individual efficacies of several specific ribozymes against PTN or ALK, respectively, antiproliferative and proapoptotic effects of a single gene targeting approach are strongly enhanced on double knockdown of both genes in vitro. More importantly, this results in the abolishment of tumor growth in an in vivo subcutaneous tumor xenograft model. Finally, the analysis of various downstream signaling pathways by antibody arrays reveals a distinct pattern of changes in the activation of signal transduction molecules on PTN/ALK double knockdown. Beyond the already known ones, it identifies additional pathways relevant for PTN/ALK signaling. We conclude that double targeting of PTN and ALK leads to enhanced antitumorigenic effects over single knockdown approaches, which offers novel therapeutic options owing to increased efficacy also after prolonged knockdown. PMID:19177199

Hypoxia enhances the wound-healing potential of adipose-derived stem cells in a novel human primary keratinocyte-based scratch assay.

PubMed

Riis, Simone; Newman, Rhonda; Ipek, Hilal; Andersen, Jens I; Kuninger, David; Boucher, Shayne; Vemuri, Mohan C; Pennisi, Cristian P; Zachar, Vladimir; Fink, Trine

2017-03-01

Preclinical studies have suggested that paracrine factors from adipose-derived stem cells (ASCs) promote the healing of chronic wounds, and that the exposure of ASCs to hypoxia enhances their wound healing effect. To aid the translation of these findings into clinical use, robust wound models are necessary to explore each aspect of wound healing. The aspect of re-epithelization is often studied in a scratch assay based on transformed keratinocytes. However, there are concerns regarding the validity of this model, since these cell lines differ from normal keratinocytes, both in terms of proliferative capacity and differentiation, and sensitivity to environmental cues. In this study, the main challenge of using primary keratinocytes to examine the effects of ASCs was identified to be their different requirements for calcium in the culture media. We confirmed that a high calcium content led to morphological and cytoskeletal changes in primary keratinocytes, and demonstrated that a low calcium content compromised the growth of ASCs. We found that it is possible to perform the wound healing assay with primary keratinocytes, if the conditioned media from the ASCs is dialyzed to reduce the calcium concentration. Additionally, using this model of re-epithelization, conditioned media from normoxic ASCs was shown to markedly increase the rate of wound closure by primary keratinocytes, and this effect was significantly enhanced with media from the hypoxia-exposed ASCs. These findings, which are in line with the observations from previous in vivo studies, highlight the validity of this modified assay to investigate the wound healing properties of ASCs in vitro.

A comparison of multi-metal deposition processes utilising gold nanoparticles and an evaluation of their application to 'low yield' surfaces for finger mark development.

PubMed

Fairley, C; Bleay, S M; Sears, V G; NicDaeid, N

2012-04-10

This paper reports a comparison of the effectiveness and practicality of using different multi-metal deposition processes for finger mark development. The work investigates whether modifications can be made to improve the performance of the existing process published by Schnetz. Secondly, we compare the ability of different multi-metal deposition processes to develop finger marks on a range of surfaces with that of other currently used development processes. All published multi-metal deposition processes utilise an initial stage of colloidal gold deposition followed by enhancement of the marks with using a physical developer. All possible combinations of colloidal gold and physical developer stages were tested. The method proposed by Schnetz was shown to be the most effective process, however a modification which reduced the pH of the enhancement solution was revealed to provide the best combination of effectiveness and practicality. In trials comparing the modified formulation with vacuum metal deposition, superglue and powder suspensions on surfaces which typically give low finger mark yields (cling film, plasticised vinyl, leather and masking tape), the modified method produced significantly better results over existing processes for cling film and plasticised vinyl. The modified formulation was found to be ineffective on both masking tape and leather. It is recommended that further tests be carried out on the modified multi-metal deposition formulation to establish whether it could be introduced for operational work on cling film material in particular. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Enhancing the reproducibility of ocular vestibular evoked myogenic potentials by use of a visual target originating from a head-mounted laser.

PubMed

Jerin, Claudia; Bartl, Klaus; Schneider, Erich; Gürkov, Robert

2015-10-01

Ocular vestibular evoked myogenic potentials (oVEMPs) represent extraocular muscle activity in response to vestibular stimulation. oVEMP amplitudes are known to increase with increasing upward gaze angle, while the patient fixates a visual target. We investigated two different methods of presenting a visual target during oVEMP recordings. 57 healthy subjects were enrolled in this study. oVEMPs were elicited by 500 Hz air-conducted tone bursts while the subjects were looking upward at a marking which was either fixed on the wall or originated from a head-mounted laser attached to a headband, in either case corresponding to a 35° upward gaze angle. oVEMP amplitudes and latencies did not differ between the subjects looking at the fixed marking and the ones looking at the laser marking. The intra-individual standard deviation of amplitudes obtained by two separate measurements for each subject, however, as a measure of test-retest reliability, was significantly smaller for the laser headband group (0.60) in comparison to the group looking at the fixed marking (0.96; p = 0.007). The intraclass correlation coefficient revealed better test-retest reliability for oVEMP amplitudes when using the laser headband (0.957) than using the fixed marking (0.908). Hence, the use of a visual target originating from a headband enhances the reproducibility of oVEMPs. This might be due to the fact that the laser headband ensures a constant gaze angle and rules out the influence of small involuntary head movements on the gaze angle.

Primary Ocular Irritation Potential of Nitrosoguanidine in Male Rabbits

DTIC Science & Technology

1989-09-01

Markedly deepened rugae , congestion, swelling, moderate circumirldial hyperemia or injection, any of these or any combination thereof, iris still...of the normal luster); inflammation of the iris (other than a slight deepening of the rugae or a slight hyperemia of the circumcomeal blood yessels

Multifocal electroretinography in patients with Stargardt's macular dystrophy

PubMed Central

Kretschmann, U; Seeliger, M; Ruether, K; Usui, T; Apfelstedt-Sylla, E; Zrenner, E

1998-01-01

AIMS—To describe the topography of multifocal electroretinograms (ERGs) and to explore its diagnostic value in patients with Stargardt's macular dystrophy (SMD).
METHODS—51 patients with SMD were examined by means of the m-sequence technique to characterise the topography of electroretinographic responses in the central visual field. The results were compared with data from 30 normal volunteers.
RESULTS—In 49 of 51 patients with SMD, macular electroretinographic activity was markedly diminished or non-detectable. Towards more peripheral areas, ERG responses of the SMD patients approached those of normals. Implicit times were not markedly delayed at any eccentricity.
CONCLUSION—In contrast with Ganzfeld electroretinography, multifocal electroretinography is useful to detect foveal dysfunction in SMD. Areas of dysfunction were found to be usually larger than expected from psychophysical measurements and morphological alteration. In early stages of the disease it was possible to detect foveal dysfunction, even in patients lacking morphological fundus changes and with good visual acuity.

 Keywords: Stargardt's macular dystrophy; fundus flavimaculatus; electroretinography PMID:9602623

Cell lineage analysis in human brain using endogenous retroelements

PubMed Central

Evrony, Gilad D.; Lee, Eunjung; Mehta, Bhaven K.; Benjamini, Yuval; Johnson, Robert M.; Cai, Xuyu; Yang, Lixing; Haseley, Psalm; Lehmann, Hillel S.; Park, Peter J.; Walsh, Christopher A.

2015-01-01

Summary Somatic mutations occur during brain development and are increasingly implicated as a cause of neurogenetic disease. However, the patterns in which somatic mutations distribute in the human brain are unknown. We used high-coverage whole-genome sequencing of single neurons from a normal individual to identify spontaneous somatic mutations as clonal marks to track cell lineages in human brain. Somatic mutation analyses in >30 locations throughout the nervous system identified multiple lineages and sub-lineages of cells marked by different LINE-1 (L1) retrotransposition events and subsequent mutation of poly-A microsatellites within L1. One clone contained thousands of cells limited to the left middle frontal gyrus, whereas a second distinct clone contained millions of cells distributed over the entire left hemisphere. These patterns mirror known somatic mutation disorders of brain development, and suggest that focally distributed mutations are also prevalent in normal brains. Single-cell analysis of somatic mutation enables tracing of cell lineage clones in human brain. PMID:25569347

Epirubicin-Adsorbed Nanodiamonds Kill Chemoresistant Hepatic Cancer Stem Cells

PubMed Central

2015-01-01

Chemoresistance is a primary cause of treatment failure in cancer and a common property of tumor-initiating cancer stem cells. Overcoming mechanisms of chemoresistance, particularly in cancer stem cells, can markedly enhance cancer therapy and prevent recurrence and metastasis. This study demonstrates that the delivery of Epirubicin by nanodiamonds is a highly effective nanomedicine-based approach to overcoming chemoresistance in hepatic cancer stem cells. The potent physical adsorption of Epirubicin to nanodiamonds creates a rapidly synthesized and stable nanodiamond–drug complex that promotes endocytic uptake and enhanced tumor cell retention. These attributes mediate the effective killing of both cancer stem cells and noncancer stem cells in vitro and in vivo. Enhanced treatment of both tumor cell populations results in an improved impairment of secondary tumor formation in vivo compared with treatment by unmodified chemotherapeutics. On the basis of these results, nanodiamond-mediated drug delivery may serve as a powerful method for overcoming chemoresistance in cancer stem cells and markedly improving overall treatment against hepatic cancers. PMID:25437772

Effects of cevimeline on the immunolocalization of aquaporin-5 and the ultrastructure of salivary glands in Sjögren's syndrome model mice.

PubMed

Nishimura, Hidehiko; Yakeishi, Akira; Saga, Tsuyoshi; Yamaki, Koh-Ichi

2009-01-01

Sjögren's syndrome (SS) is an autoimmune disorder whose main symptoms include xerostomia and dry eyes. It has been demonstrated that abnormal expression of aquaporin (AQP)-5 in the parotid and submandibular glands in SS model mice was corrected by cevimeline. In the present study, we orally administered cevimeline hydrochloride (cevimeline) to female MRL/l mice, which are widely used as a model for SS, to immunohistochemically investigate the localization of AQP-5 in the salivary glands. We also assessed the ultrastructure of acinar cells in the submandibular glands. AQP-5 was expressed in the apical and lateral cell membranes of acinar cells in the parotid and submandibular glands of normal mice, but not in the sublingual glands. In contrast, AQP-5 was expressed not only in the cell membranes in the apical domains but also in the cytoplasm in the SS model mice, indicating that the localization of AQP-5 was disordered in the SS model mice. After administration of cevimeline, AQP-5 was predominantly localized in the cellular apical domains of the acinar cells. Electron microscopy revealed that administration of cevimeline to the SS model mice and normal mice markedly reduced the number of secretory granules, increased the area of the rough endoplasmic reticulum, and expanded the intercellular gaps in the cells of the submandibular acini. Condensed vacuoles were also observed in the Golgi apparatuses, indicating that secondary enhancement of secretion and production of saliva had occurred. Consequently, the results of the present study demonstrate that the administration of cevimeline to the SS model mice increased salivary secretion in the submandibular glands. Furthermore, cevimeline transiently normalized the localization of AQP-5 expression in the parotid and submandibular glands.

T-wave morphology can distinguish healthy controls from LQTS patients.

PubMed

Immanuel, S A; Sadrieh, A; Baumert, M; Couderc, J P; Zareba, W; Hill, A P; Vandenberg, J I

2016-09-01

Long QT syndrome (LQTS) is an inherited disorder associated with prolongation of the QT/QTc interval on the surface electrocardiogram (ECG) and a markedly increased risk of sudden cardiac death due to cardiac arrhythmias. Up to 25% of genotype-positive LQTS patients have QT/QTc intervals in the normal range. These patients are, however, still at increased risk of life-threatening events compared to their genotype-negative siblings. Previous studies have shown that analysis of T-wave morphology may enhance discrimination between control and LQTS patients. In this study we tested the hypothesis that automated analysis of T-wave morphology from Holter ECG recordings could distinguish between control and LQTS patients with QTc values in the range 400-450 ms. Holter ECGs were obtained from the Telemetric and Holter ECG Warehouse (THEW) database. Frequency binned averaged ECG waveforms were obtained and extracted T-waves were fitted with a combination of 3 sigmoid functions (upslope, downslope and switch) or two 9th order polynomial functions (upslope and downslope). Neural network classifiers, based on parameters obtained from the sigmoid or polynomial fits to the 1 Hz and 1.3 Hz ECG waveforms, were able to achieve up to 92% discrimination between control and LQTS patients and 88% discrimination between LQTS1 and LQTS2 patients. When we analysed a subgroup of subjects with normal QT intervals (400-450 ms, 67 controls and 61 LQTS), T-wave morphology based parameters enabled 90% discrimination between control and LQTS patients, compared to only 71% when the groups were classified based on QTc alone. In summary, our Holter ECG analysis algorithms demonstrate the feasibility of using automated analysis of T-wave morphology to distinguish LQTS patients, even those with normal QTc, from healthy controls.

Evidence for inhibitory nicotinic and facilitatory muscarinic receptors in cholinergic nerve terminals of the rat urinary bladder.

PubMed

Somogyi, G T; de Groat, W C

1992-02-01

Cholinergic prejunctional modulatory receptors on parasympathetic nerves in the rat urinary bladder were studied by measuring 3H-acetylcholine (ACh) release in muscle strips from the bladder body. Electrical field stimulation markedly increased 3H-ACh overflow in strips preloaded with 3H-choline. Oxotremorine (1 microM), an M2 receptor agonist and DMPP (10 microM) a nicotinic (N) receptor agonist decreased the release of ACh (50% and 55% respectively); whereas McN-A 343 (50 microM) an M1 receptor agonist increased the release (33%), indicating the presence of three types of modulatory receptors. The anticholinesterase agent, physostigmine in concentrations of 1, 5 and 25 microM and neostigmine (5 microM) increased ACh release (44-710%). However a low concentration of physostigmine (0.05 microM) decreased release. Pirenzepine, an M1 muscarinic antagonist or atropine blocked the increased ACh release in physostigmine-treated strips, but in normal strips pirenzepine did not change release and atropine increased release. McN-A 343 or prolonged application (15 min) of DMPP increased ACh release (376% and 391% respectively) in physostigmine-treated strips. The response to McN-A 343 was blocked by pirenzepine. d-Tubocurarine (DTC), a nicotinic receptor blocker, enhanced ACh release in the presence of physostigmine but proved to be ineffective in normal preparations. These findings suggest that all three cholinergic receptors (M1 facilitatory, N inhibitory and M2 inhibitory) are activated by endogenous ACh in physostigmine treated preparations whereas only M2-inhibitory receptors are activated in normal preparations. It will be important in future studies to determine whether M1 and M2 mechanisms can also be activated under more physiological conditions in the bladder and whether they are present at other cholinergic synapses.

Versican Promotes Tumor Progression, Metastasis and Predicts Poor Prognosis in Renal Carcinoma.

PubMed

Mitsui, Yozo; Shiina, Hiroaki; Kato, Taku; Maekawa, Shigekatsu; Hashimoto, Yutaka; Shiina, Marisa; Imai-Sumida, Mitsuho; Kulkarni, Priyanka; Dasgupta, Pritha; Wong, Ryan Kenji; Hiraki, Miho; Arichi, Naoko; Fukuhara, Shinichiro; Yamamura, Soichiro; Majid, Shahana; Saini, Sharanjot; Deng, Guoren; Dahiya, Rajvir; Nakajima, Koichi; Tanaka, Yuichiro

2017-07-01

The proteoglycan versican (VCAN) promotes tumor progression and enhances metastasis in several cancers; however, its role in clear cell renal cell carcinoma (ccRCC) remains unknown. Recent evidence suggests that VCAN is an important target of chromosomal 5q gain, one of the most prevalent genetic abnormalities in ccRCC. Thus, we investigated whether VCAN expression is associated with the pathogenesis of ccRCC. VCAN expression was analyzed using three RCC and normal kidney cell lines as well as a clinical cohort of 84 matched ccRCC and normal renal tissues. Functional analyses on growth and progression properties were performed using VCAN-depleted ccRCC cells. Microarray expression profiling was employed to investigate the target genes and biologic pathways involved in VCAN-mediated ccRCC carcinogenesis. ccRCC had elevated VCAN expression in comparison with normal kidney in both cell lines and clinical specimens. The elevated expression of VCAN was significantly correlated with metastasis ( P < 0.001) and worse 5-year overall survival after radical nephrectomy ( P = 0.014). In vitro , VCAN knockdown significantly decreased cell proliferation and increased apoptosis in Caki-2 and 786-O cells, and this was associated with alteration of several TNF signaling-related genes such as TNFα, BID , and BAK Furthermore, VCAN depletion markedly decreased cell migration and invasion which correlated with reduction of MMP7 and CXCR4. These results demonstrate that VCAN promotes ccRCC tumorigenesis and metastasis and thus is an attractive target for novel diagnostic, prognostic, and therapeutic strategies. Implications: This study highlights the oncogenic role of VCAN in renal cell carcinogenesis and suggests that this gene has therapeutic and/or biomarker potential for renal cell cancer. Mol Cancer Res; 15(7); 884-95. ©2017 AACR . ©2017 American Association for Cancer Research.

Selective Roles of Normal and Mutant Huntingtin in Neural Induction and Early Neurogenesis

PubMed Central

Nguyen, Giang D.; Gokhan, Solen; Molero, Aldrin E.; Mehler, Mark F.

2013-01-01

Huntington's disease (HD) is a neurodegenerative disorder caused by abnormal polyglutamine expansion in the amino-terminal end of the huntingtin protein (Htt) and characterized by progressive striatal and cortical pathology. Previous reports have shown that Htt is essential for embryogenesis, and a recent study by our group revealed that the pathogenic form of Htt (mHtt) causes impairments in multiple stages of striatal development. In this study, we have examined whether HD-associated striatal developmental deficits are reflective of earlier maturational alterations occurring at the time of neurulation by assessing differential roles of Htt and mHtt during neural induction and early neurogenesis using an in vitro mouse embryonic stem cell (ESC) clonal assay system. We demonstrated that the loss of Htt in ESCs (KO ESCs) severely disrupts the specification of primitive and definitive neural stem cells (pNSCs, dNSCs, respectively) during the process of neural induction. In addition, clonally derived KO pNSCs and dNSCs displayed impaired proliferative potential, enhanced cell death and altered multi-lineage potential. Conversely, as observed in HD knock-in ESCs (Q111 ESCs), mHtt enhanced the number and size of pNSC clones, which exhibited enhanced proliferative potential and precocious neuronal differentiation. The transition from Q111 pNSCs to fibroblast growth factor 2 (FGF2)-responsive dNSCs was marked by potentiation in the number of dNSCs and altered proliferative potential. The multi-lineage potential of Q111 dNSCs was also enhanced with precocious neurogenesis and oligodendrocyte progenitor elaboration. The generation of Q111 epidermal growth factor (EGF)-responsive dNSCs was also compromised, whereas their multi-lineage potential was unaltered. These abnormalities in neural induction were associated with differential alterations in the expression profiles of Notch, Hes1 and Hes5. These cumulative observations indicate that Htt is required for multiple stages of neural induction, whereas mHtt enhances this process and promotes precocious neurogenesis and oligodendrocyte progenitor cell elaboration. PMID:23691206

Ionizing irradiation not only inactivates clonogenic potential in primary normal human diploid lens epithelial cells but also stimulates cell proliferation in a subset of this population.

PubMed

Fujimichi, Yuki; Hamada, Nobuyuki

2014-01-01

Over the past century, ionizing radiation has been known to induce cataracts in the crystalline lens of the eye, but its mechanistic underpinnings remain incompletely understood. This study is the first to report the clonogenic survival of irradiated primary normal human lens epithelial cells and stimulation of its proliferation. Here we used two primary normal human cell strains: HLEC1 lens epithelial cells and WI-38 lung fibroblasts. Both strains were diploid, and a replicative lifespan was shorter in HLEC1 cells. The colony formation assay demonstrated that the clonogenic survival of both strains decreases similarly with increasing doses of X-rays. A difference in the survival between two strains was actually insignificant, although HLEC1 cells had the lower plating efficiency. This indicates that the same dose inactivates the same fraction of clonogenic cells in both strains. Intriguingly, irradiation enlarged the size of clonogenic colonies arising from HLEC1 cells in marked contrast to those from WI-38 cells. Such enhanced proliferation of clonogenic HLEC1 cells was significant at ≥2 Gy, and manifested as increments of ≤2.6 population doublings besides sham-irradiated controls. These results suggest that irradiation of HLEC1 cells not only inactivates clonogenic potential but also stimulates proliferation of surviving uniactivated clonogenic cells. Given that the lens is a closed system, the stimulated proliferation of lens epithelial cells may not be a homeostatic mechanism to compensate for their cell loss, but rather should be regarded as abnormal. This is because these findings are consistent with the early in vivo evidence documenting that irradiation induces excessive proliferation of rabbit lens epithelial cells and that suppression of lens epithelial cell divisions inhibits radiation cataractogenesis in frogs and rats. Thus, our in vitro model will be useful to evaluate the excessive proliferation of primary normal human lens epithelial cells that may underlie radiation cataractogenesis, warranting further investigations.

Comprehensive Analysis of Genome Rearrangements in Eight Human Malignant Tumor Tissues

PubMed Central

Wang, Chong

2016-01-01

Carcinogenesis is a complex multifactorial, multistage process, but the precise mechanisms are not well understood. In this study, we performed a genome-wide analysis of the copy number variation (CNV), breakpoint region (BPR) and fragile sites in 2,737 tumor samples from eight tumor entities and in 432 normal samples. CNV detection and BPR identification revealed that BPRs tended to accumulate in specific genomic regions in tumor samples whereas being dispersed genome-wide in the normal samples. Hotspots were observed, at which segments with similar alteration in copy number were overlapped along with BPRs adjacently clustered. Evaluation of BPR occurrence frequency showed that at least one was detected in about and more than 15% of samples for each tumor entity while BPRs were maximal in 12% of the normal samples. 127 of 2,716 tumor-relevant BPRs (termed ‘common BPRs’) exhibited also a noticeable occurrence frequency in the normal samples. Colocalization assessment identified 20,077 CNV-affecting genes and 169 of these being known tumor-related genes. The most noteworthy genes are KIAA0513 important for immunologic, synaptic and apoptotic signal pathways, intergenic non-coding RNA RP11-115C21.2 possibly acting as oncogene or tumor suppressor by changing the structure of chromatin, and ADAM32 likely importance in cancer cell proliferation and progression by ectodomain-shedding of diverse growth factors, and the well-known tumor suppressor gene p53. The BPR distributions indicate that CNV mutations are likely non-random in tumor genomes. The marked recurrence of BPRs at specific regions supports common progression mechanisms in tumors. The presence of hotspots together with common BPRs, despite its small group size, imply a relation between fragile sites and cancer-gene alteration. Our data further suggest that both protein-coding and non-coding genes possessing a range of biological functions might play a causative or functional role in tumor biology. This research enhances our understanding of the mechanisms for tumorigenesis and progression. PMID:27391163

MESSENGER Observations of Mercury's Magnetosphere

NASA Technical Reports Server (NTRS)

Slavin, James A.

2010-01-01

During MESSENGER's second and third flybys of Mercury on October 6, 2008 and September 29, 2009, respectively, southward interplanetary magnetic field (IMF) produced intense reconnection signatures in the dayside and nightside magnetosphere and markedly different system-level responses. The IMF during the second flyby was continuously southward and the magnetosphere appeared very active, with large magnetic field components normal to the magnetopause and the generation of flux transfer events at the magnetopause and plasmoids in the tail current sheet every 30 to 90 s. However, the strength and direction of the tail magnetic field was stable. In contrast, the IMF during the third flyby varied from north to south on timescales of minutes. Although the MESSENGER measurements were limited during that encounter to the nightside magnetosphere, numerous examples of plasmoid release in the tail were detected, but they were not periodic. Instead, plasmoid release was highly correlated with four large enhancements of the tail magnetic field (i.e. by factors > 2) with durations of approx. 2 - 3 min. The increased flaring of the magnetic field during these intervals indicates that the enhancements were caused by loading of the tail with magnetic flux transferred from the dayside magnetosphere. New analyses of the second and third flyby observations of reconnection and its system-level effects provide a basis for comparison and contrast with what is known about the response of the Earth s magnetosphere to variable versus steady southward IMF.

Transient Encephalopathy from Angiographic Contrast: A Rare Complication in Neurointerventional Procedures

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

Guimaraens, Leopoldo, E-mail: guimaraens@mimsl.es; Vivas, Elio; Fonnegra, Andres

Neurotoxicity from contrast media used in angiography is a rare complication from these procedures. The infrequency with which it is encountered makes it a diagnostic challenge. We present the case of a 51-year-old male who, 30 min after successful angiography for treatment of a right carotid-ophthalmic fusiform aneurysm with a stent, developed psychomotor agitation, disorientation, and progressive left faciobrachial hemiparesis (4/5). An emergency nonenhanced CT showed marked cortical enhancement and edema in the right cerebral hemisphere. Cortical enhancement is thought to be secondary to contrast extravasation due to disruption of the blood-brain barrier. Angiography was performed immediately, without any pathologicmore » findings. After this procedure there was an increase in the left faciobrachial hemiparesis (3/5), right gaze deviation, Gerstmann syndrome, and left anosognosia and left homonymous hemianopsia. Endovenous dexamethasone and mannitol were initiated. Twenty-four hours later an MRI showed no signs of acute infarct, just gyriform signal increase in the right cerebral hemisphere on FLAIR and a decrease in the edema observed before. The patient had progressive improvement of his neurological deficit. A control MRI done 5 days later was normal. The patient recovered completely and was discharged. This rare entity should be kept in mind but diagnosed only when all other causes have been ruled out, because more important and frequent causes, such as acute infarct, must be excluded promptly.« less

Metabolic brain imaging correlated with clinical features of brain tumors

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

Alavi, J.; Alavi, A.; Dann, R.

1985-05-01

Nineteen adults with brain tumors have been studied with positron emission tomography utilizing FDG. Fourteen had biopsy proven cerebral malignant glioma, one each had meningioma, hemangiopericytoma, primitive neuroectodermal tumor (PNET), two had unbiopsied lesions, and one patient had an area of biopsy proven radiation necrosis. Three different patterns of glucose metabolism are observed: marked increase in metabolism at the site of the known tumor in (10 high grade gliomas and the PNET), lower than normal metabolism at the tumor (in 1 grade II glioma, 3 grade III gliomas, 2 unbiopsied low density nonenhancing lesions, and the meningioma), no abnormality (1more » enhancing glioma, the hemangiopericytoma and the radiation necrosis.) The metabolic rate of the tumor or the surrounding brain did not appear to be correlated with the history of previous irradiation or chemotherapy. Decreased metabolism was frequently observed in the rest of the affected hemisphere and in the contralateral cerebellum. Tumors of high grade or with enhancing CT characteristics were more likely to show increased metabolism. Among the patients with proven gliomas, survival after PETT scan tended to be longer for those with low metabolic activity tumors than for those with highly active tumors. The authors conclude that PETT may help to predict the malignant potential of tumors, and may add useful clinical information to the CT scan.« less

Immunomodulatory effect of a formula developed from American ginseng and Chinese jujube extracts in mice.

PubMed

Yu, Zhuo-ping; Xu, Dong-dong; Lu, Lai-feng; Zheng, Xiao-dong; Chen, Wei

2016-02-01

American ginseng (Panax quinquefolius L.) and Chinese jujube (Zizyphus jujuba Mill.) are commonly used in traditional Chinese medicine to enhance immune function. The present study aimed to develop one Chinese prescription, Shenzao Cha (SZC), consisting of American ginseng and Chinese jujube, and systematically investigate its immunomodulation in healthy ICR mice. Normal ICR mice received intragastric administration of SZC (1.3, 2.6, and 5.2 g raw material/kg body weight) once daily for four weeks, while a control group received the same amount of sterile water. SZC significantly increased the spleen and thymus indices and T-lymphocyte proliferation, while the T-lymphocyte proliferation in the 5.2 g/kg group was 1.4-fold higher than that in the control. Further, 1.3 g/kg SZC could markedly improve hemolytic activity by 25.2%, and 2.6 g/kg SZC increased the NK cell activity by 78.6% relative to the control. In addition, the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), that participated in modulating oxidative stress, were significantly increased in the liver, spleen, thymus, and serum, while the contents of malondialdehyde were dramatically decreased. SZC exhibited potent immunomodulatory effects on innate and adaptive immunity in healthy ICR mice, as well as potential antioxidant activity for prevention of oxidative stress, which was suggested to partly contribute to the immune enhancement.

Calreticulin Enhances Porcine Wound Repair by Diverse Biological Effects

PubMed Central

Nanney, Lillian B.; Woodrell, Christopher D.; Greives, Mathew R.; Cardwell, Nancy L.; Pollins, Alonda C.; Bancroft, Tara A.; Chesser, Adrianne; Michalak, Marek; Rahman, Mohammad; Siebert, John W.; Gold, Leslie I.

2008-01-01

Extracellular functions of the endoplasmic reticulum chaperone protein calreticulin (CRT) are emerging. Here we show novel roles for exogenous CRT in both cutaneous wound healing and diverse processes associated with repair. Compared with platelet-derived growth factor-BB-treated controls, topical application of CRT to porcine excisional wounds enhanced the rate of wound re-epithelialization. In both normal and steroid-impaired pigs, CRT increased granulation tissue formation. Immunohistochemical analyses of the wounds 5 and 10 days after injury revealed marked up-regulation of transforming growth factor-β3 (a key regulator of wound healing), a threefold increase in macrophage influx, and an increase in the cellular proliferation of basal keratinocytes of the new epidermis and of cells of the neodermis. In vitro studies confirmed that CRT induced a greater than twofold increase in the cellular proliferation of primary human keratinocytes, fibroblasts, and microvascular endothelial cells (with 100 pg/ml, 100 ng/ml, and 1.0 pg/ml, respectively). Moreover, using a scratch plate assay, CRT maximally induced the cellular migration of keratinocytes and fibroblasts (with 10 pg/ml and 1 ng/ml, respectively). In addition, CRT induced concentration-dependent migration of keratinocytes, fibroblasts macrophages, and monocytes in chamber assays. These in vitro bioactivities provide mechanistic support for the positive biological effects of CRT observed on both the epidermis and dermis of wounds in vivo, underscoring a significant role for CRT in the repair of cutaneous wounds. PMID:18753412

High Intensity Interval Training Increases Natural Killer Cell Number and Function in Obese Breast Cancer-challenged Mice and Obese Women.

PubMed

Barra, Nicole G; Fan, Isabella Y; Gillen, Jenna B; Chew, Marianne; Marcinko, Katarina; Steinberg, Gregory R; Gibala, Martin J; Ashkar, Ali A

2017-12-01

High intensity interval training (HIIT) boosts natural killer (NK) cell number and activity in normal weight breast cancer patients; however, whether this occurs in obese individuals is not well established. The goal of this study was to determine whether HIIT effectively boosts NK cells as a therapeutic strategy against breast cancer in an obese mouse model and in overweight/obese women. Diet induced female C57Bl/6 obese mice were assigned to undergo HIIT for four weeks or remain sedentary. Female participants were subjected to a six weeks HIIT protocol. HIIT mice acclimatized to treadmill running were subsequently injected with 5 × 10 5 polyoma middle T (MT) breast cancer cells intravenously. NK cell number and activation were monitored using flow cytometry, and tumor burden or lipid content evaluated from histological lung and liver tissues, respectively. In both mice and humans, circulating NK cell number and activation (CD3-NK1.1+CD27+ and CD3-CD56+, respectively) markedly increased immediately after HIIT. HIIT obese mice had reduced lung tumor burden compared to controls following MT challenge, and had diminished hepatic lipid deposition despite minimal body weight loss. Our findings demonstrate that HIIT can benefit obese individuals by enhancing NK cell number and activity, reducing tumor burden, and enhancing metabolic health.

High Intensity Interval Training Increases Natural Killer Cell Number and Function in Obese Breast Cancer-challenged Mice and Obese Women

PubMed Central

Barra, Nicole G.; Fan, Isabella Y.; Gillen, Jenna B.; Chew, Marianne; Marcinko, Katarina; Steinberg, Gregory R.; Gibala, Martin J.; Ashkar, Ali A.

2017-01-01

High intensity interval training (HIIT) boosts natural killer (NK) cell number and activity in normal weight breast cancer patients; however, whether this occurs in obese individuals is not well established. The goal of this study was to determine whether HIIT effectively boosts NK cells as a therapeutic strategy against breast cancer in an obese mouse model and in overweight/obese women. Diet induced female C57Bl/6 obese mice were assigned to undergo HIIT for four weeks or remain sedentary. Female participants were subjected to a six weeks HIIT protocol. HIIT mice acclimatized to treadmill running were subsequently injected with 5 × 105 polyoma middle T (MT) breast cancer cells intravenously. NK cell number and activation were monitored using flow cytometry, and tumor burden or lipid content evaluated from histological lung and liver tissues, respectively. In both mice and humans, circulating NK cell number and activation (CD3−NK1.1+CD27+ and CD3−CD56+, respectively) markedly increased immediately after HIIT. HIIT obese mice had reduced lung tumor burden compared to controls following MT challenge, and had diminished hepatic lipid deposition despite minimal body weight loss. Our findings demonstrate that HIIT can benefit obese individuals by enhancing NK cell number and activity, reducing tumor burden, and enhancing metabolic health. PMID:29302585

Further studies on the effect of nitrogen dioxide on mast cells: The effect of the metabolite, nitrite

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

Fujimaki, Hidekazu; Ozawa, Masashi; Bissonnette, E.

1993-05-01

To evaluate the relationship between atmospheric nitrogen dioxide exposure and the development of allergic diseases, the effects of nitrite as a chemical product of inhaled nitrogen dioxide on mast cell functions were investigated. We have studied nitride-induced histamine release from two functionally distinct mast cell populations, namely peritoneal mast cells (PMC) and intestinal mucosal mast cells (IMMC) of Nippostrongylus brasiliensis-infected rats. High concentrations of nitrite alone (10, 20, and 50 mM) induced histamine release from IMMC, but not from PMC. Moreover, histamine release from PMC and IMMC stimulated with sensitizing antigen was significantly enhanced by pretreatment with 50 mM nitritemore » or nitrate. No differences in histamine release from nitrite-treated and control PMC were seen below 1 mM. To investigate the effect of nitrite on tumor cell cytotoxic activity, PMC were incubated with various concentrations of nitrite. Pretreatment with 5 and 50 mM nitrite markedly depressed tumor necrosis factor (TNF)-[alpha]-dependent natural cytotoxicity of PMC for the tumor target WEHI-164. Thus, high concentrations of nitrite enhanced mast cell histamine release, but depressed TNF-[alpha]-dependent cytotoxicity. However, low concentrations of nitrite (<1 mM) that would normally be produced by short-term atmospheric exposure to nitrogen dioxide may have no significant effects on mast cell functions. 27 refs., 3 figs., 1 tab.« less

78 FR 33326 - Intermediary Relending Program; Roundtable Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-04

... enhancements to the Intermediary Relending Program (IRP) and fiscal year 2013 funding levels and application... sign language interpreter or other special accommodations should contact Mark Brodziski as identified...

Improvement to the scanning electron microscope image adaptive Canny optimization colorization by pseudo-mapping.

PubMed

Lo, T Y; Sim, K S; Tso, C P; Nia, M E

2014-01-01

An improvement to the previously proposed adaptive Canny optimization technique for scanning electron microscope image colorization is reported. The additional feature, called pseudo-mapping technique, is that the grayscale markings are temporarily mapped to a set of pre-defined pseudo-color map as a mean to instill color information for grayscale colors in chrominance channels. This allows the presence of grayscale markings to be identified; hence optimization colorization of grayscale colors is made possible. This additional feature enhances the flexibility of scanning electron microscope image colorization by providing wider range of possible color enhancement. Furthermore, the nature of this technique also allows users to adjust the luminance intensities of selected region from the original image within certain extent. © 2014 Wiley Periodicals, Inc.

Speed-Up Techniques for Complementary Metal Oxide Semiconductor Very Large Scale Integration.

DTIC Science & Technology

1984-12-14

The input voltage at which the two transistors are in the constant current region at the same time marks the active operating region of the inverter...decoder precharge configurations. One circuit displayed a marked enhancement in operation while the other precharged circuit displyed degraded operation due...34 IEEE Journal of Solid State Circuits, SC-18: 457-462 (October 1983). 19. Cobbold , R. Theory and Applications of Field Effect Transistors, New York: John

Pseudohypoparathyroidism: defective excretion of 3′,5′-AMP in response to parathyroid hormone

PubMed Central

Chase, Lewis R.; Melson, G. Leland; Aurbach, G. D.

1969-01-01

Urinary excretion of cyclic adenosine 3′,5′-monophosphate (3′,5′-AMP) was tested in normal subjects and patients with pseudohypoparathyroidism, idiopathic hypoparathyroidism, surgical hypoparathyroidism, and pseudopseudohypoparathyroidism under basal conditions and after a 15 min infusion of purified parathyroid hormone. Basal excretion of the nucleotide was less than normal in the patients with hypocalcemic disorders and greater than normal in pseudopseudohypoparathyroidism. Parathyroid hormone caused a marked increase in excretion of 3′,5′-AMP in all subjects except those with pseudohypoparathyroidism; nine patients with this disorder did not respond to the hormone and four showed a markedly deficient response. Radioimmunoassay showed that parathyroid hormone circulated in increased amounts in plasma from patients with pseudohypoparathyroidism and became undetectable when serum calcium was increased above 12 mg/100 ml. Suppression of parathyroid hormone secretion by induction of hypercalcemia did not alter the deficient response to exogenous hormone. The results indicate that: (a) parathyroid hormone circulates in abnormally high concentrations in pseudohypoparathyroidism and secretion of the hormone responds normally to physiological control by calcium; (b) testing urinary excretion of 3′,5′-AMP in response to infusion of purified parathyroid hormone appears to be an accurate and sensitive index for establishing the diagnosis of pseudohypoparathyroidism; and (c) the metabolic defect of the disorder can be accounted for by a lack of or defective form of parathyroid hormone-sensitive adenyl cyclase in bone and kidney. PMID:4309802

Differential MR Delayed Enhancement Patterns of Chronic Myocardial Infarction between Extracellular and Intravascular Contrast Media

PubMed Central

Wang, Jian; Xiang, Bo; Lin, Hung Yu; Liu, Hongyu; Freed, Darren; Arora, Rakesh C.; Tian, Ganghong

2015-01-01

Objectives Because the distribution volume and mechanism of extracellular and intravascular MR contrast media differ considerably, the enhancement pattern of chronic myocardial infarction with extracellular or intravascular media might also be different. This study aims to investigate the differences in MR enhancement patterns of chronic myocardial infarction between extracellular and intravascular contrast media. Materials and Methods Twenty pigs with myocardial infarction underwent cine MRI, first pass perfusion MRI and delayed enhancement MRI with extracellular or intravascular media at four weeks after coronary occlusion. Myocardial blood flow (MBF) was determined with microsphere measurement. The infarction histopathological changes were evaluated by hematoxylin and eosin staining and Masson's trichrome method. Results Cine MRI revealed the reduced wall thickening in chronic infarction compared with normal myocardium. Moreover, significant wall thinning in chronic infarction was observed in cine MRI. Peak first-pass signal intensity didn’t significantly differ between chronic infarction and normal myocardium no matter what kinds of contrast media. At the following delayed enhancement phase, extracellular media-enhanced signal intensity was significantly higher in chronic infarction than in normal myocardium. Conversely, intravascular media-enhanced signal intensity was almost equivalent among chronic infarction and normal myocardium. At four weeks after infarction, MBF in chronic infarction approached to that in normal myocardium. Large thick-walled vessels were detected at peri-infarction zones. The cardiomyocytes were replaced by scar tissue consisting of dilated blood vessels and discrete fibers of collagen. Conclusions Chronic infarction was characterized by the significantly reduced wall thickening and the definite wall thinning. First-pass myocardial perfusion defect was not detected in chronic infarction with two media due to the significantly recovered MBF and well-developed collateral vessels. Infarction remodeling enlarged the extracellular compartment, which was available for extracellular media but not accessible to intravascular media. Extracellular media identified chronic infarction as the hyper-enhancement; nonetheless, intravascular media didn’t provide delayed enhancement. PMID:25816056

Enhanced contractility of the rat stomach during suppression of angiotensin converting enzyme by captopril in vitro.

PubMed

Rani, R; Rao, K S

1991-04-01

1. Intragastric pressure (IGP) was used as an index, of the effect of serosal application of captopril (SQ 14,225; D-3-mercapto-2-methylpropanoyl-L-proline) on the contractility of rat stomach in vitro. 2. Captopril, at concentrations greater than 0.3 microM, enhanced the spontaneous gastric motility (GM) in a concentration-dependent manner whereas concentrations less than 0.3 microM selectively potentiated 4 nM bradykinin (BK)-evoked gastric contractions without significantly affecting the spontaneous GM. 3. The kallikrein inhibitor, aprotinin (100 u ml-1), markedly antagonized the enhanced GM to 1.4 microM captopril and BK (4 nM)-evoked contractions, without affecting the contractions evoked by angiotensin 1 (10 nM) and acetylcholine (0.4 microM). The angiotensin II antagonist, saralasin (50 microM) failed to mimic aprotinin. 4. The enhanced GM to captopril was markedly inhibited by tetrodotoxin (1 microM), and partially inhibited by atropine (1 microM). 5. These results indicate that in vitro, captopril (greater than 0.3 microM) enhances gastric contractility through kininase/ACE inhibitory action, presumably by increasing the concentration of undegraded tissue kinins and substance P. This motor response seems to be predominantly due to activation of the cholinergic neurones but non-cholinergic excitatory neurones are also involved.

Calcifying supracoracoid bursitis as a cause of chronic shoulder pain.

PubMed Central

Mens, J; van der Korst, J K

1984-01-01

A case of chronic shoulder pain is reported with marked limitation of both active and passive elevations and a normal range of motion of the glenohumeral joint. X-ray examination demonstrated cloudy calcification in the coracoclavicular region, presumably indicating calcifying supracoracoid bursitis. Images PMID:6497468

The northeast water supply crisis of the 1960's

USGS Publications Warehouse

Barksdale, Henry C.

1968-01-01

The water supply drought in the Northeast began in the autumn of 1961 and marked the beginning of a severe water shortage that continued with little relief through the summer of 1966. During this time, throughout much of the Northeast, water supplies remained below normal.

Possible carcinogenic potential of dimethyl dimethoxy biphenyl dicarboxylate in experimental animals

PubMed Central

Botros, Sanaa Sabet; El-Lakkany, Naglaa Mohamed; Hammam, Olfat Ali; Sabra, Abdel-Naser Abdel-Aal; Taha, Alaa Awad

2016-01-01

Dimethyl dimethoxy biphenyl dicarboxylate (DDB) has been extensively used in the treatment of liver diseases accounting for 1–6% of the global disease burden. Cell replication, DNA synthesis, and proliferation, providing significant information about behavior of cells were examined in mice exposed to subchronic administration with DDB. Conventional liver functions specifically gamma-glutamyltransferase (γ-GT), a marker expressing liver canceration was also investigated. Normal mice were allocated into two groups each of 10 mice. The 1st and 2nd groups were treated with DDB in a dose of 50 mg/kg/day, 5 days/week for 1 month and 3 months, respectively. Comparable groups of normal mice were left without treatment as controls. Compared to normal control group, animals receiving DDB for 3 months showed marked elevations of both alanine aminotransferase and γ-GT, significant inhibition in cytochrome P450, a significant increase in the mean ploidy and 4C with moderate to marked increase in S-phase populations and the number of proliferating cell nuclear antigen-positive cells. In conclusion, this is the first report on the potential relationship between the subchronic administration of DDB and the increase in the hepatocyte proliferation, cell replication and DNA synthesis that may raise an alarm regarding possible DDB insult on the biological behavior of cells. PMID:27144153

The effect of abnormal colour vision on the ability to identify and outline coloured clinical signs and to count stained bacilli in sputum.

PubMed

Campbell, John L; Griffin, Lewis; Spalding, J Anthony B; Mir, Fraz A

2005-11-01

To determine if medical practitioners with congenital colour vision deficiencies (CCVD) are less able to identify and delineate the extent of coloured abnormal signs than those with normal colour vision. Twenty-two medical practitioners with CCVD and 17 with normal colour vision, matched for age and gender, were shown 10 photographs. They were asked to identify and outline the extent of the clinical sign in eight that were of vomit or stool (six of these showing fresh blood), one of a skin rash and for one to mark the position of bacilli in sputum stained by the Ziehl-Neelsen method. There were statistically significant differences between the CCVD practitioners and those with normal colour vision in their ability to outline abnormalities in five of the six photographs that showed fresh blood, in the photograph of a rash and in marking the position of bacilli in the photograph of a stained slide. Medical practitioners with CCVD are handicapped in their evaluation of the presence and extent of coloured clinical signs. Medical schools should ensure that students with CCVD are aware of their deficiency and know its severity, so they can take special care in clinical practice.

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...

The effect of mark enhancement techniques on the subsequent detection of saliva.

PubMed

McAllister, Patricia; Graham, Eleanor; Deacon, Paul; Farrugia, Kevin J

2016-09-01

There appears to be a limited but growing body of research on the sequential analysis/treatment of multiple types of evidence. The development of an integrated forensic approach is necessary to maximise evidence recovery and to ensure that a particular treatment is not detrimental to other types of evidence. This study aims to assess the effect of latent and blood mark enhancement techniques (e.g. fluorescence, ninhydrin, acid violet 17, black iron-oxide powder suspension) on the subsequent detection of saliva. Saliva detection was performed by means of a presumptive test (Phadebas®) in addition to analysis by a rapid stain identification (RSID) kit test and confirmatory DNA testing. Additional variables included a saliva depletion series and a number of different substrates with varying porosities as well as different ageing periods. Examination and photography under white light and fluorescence was carried out prior to and after chemical enhancement. All enhancement techniques (except Bluestar® Forensic Magnum luminol) employed in this study resulted in an improved visualisation of the saliva stains, although the inherent fluorescence of saliva was sometimes blocked after chemical treatment. The use of protein stains was, in general, detrimental to the detection of saliva. Positive results were less pronounced after the use of black iron-oxide powder suspension, cyanoacrylate fuming followed by BY40 and ninhydrin when compared to the respective positive controls. The application of Bluestar® Forensic Magnum luminol and black magnetic powder proved to be the least detrimental, with no significant difference between the test results and the positive controls. The use of non-destructive fluorescence examination provided good visualisation; however, only the first few marks in the depletion were observed. Of the samples selected for DNA analysis only depletion 1 samples contained sufficient DNA quantity for further processing using standard methodology. The 28-day delay between sample deposition and collection resulted in a 5-fold reduction in the amount of useable DNA. When sufficient DNA quantities were recovered, enhancement techniques did not have a detrimental effect on the ability to generate DNA profiles. This study aims to contribute to a strategy for maximising evidence recovery and efficiency for the detection of latent marks and saliva. The results demonstrate that most of the enhancement techniques employed in this study were not detrimental to the subsequent detection of saliva by means of presumptive, confirmative and DNA tests. Copyright © 2016 The Chartered Society of Forensic Sciences. Published by Elsevier Ireland Ltd. All rights reserved.

The examination and identification of bite marks in foods using 3D scanning and 3D comparison methods.

PubMed

Naether, Silvio; Buck, Ursula; Campana, Lorenzo; Breitbeck, Robert; Thali, Michael

2012-01-01

Bite mark analysis offers the opportunity to identify the biter based on the individual characteristics of the dentitions. Normally, the main focus is on analysing bite mark injuries on human bodies, but also, bite marks in food may play an important role in the forensic investigation of a crime. This study presents a comparison of simulated bite marks in different kinds of food with the dentitions of the presumed biter. Bite marks were produced by six adults in slices of buttered bread, apples, different kinds of Swiss chocolate and Swiss cheese. The time-lapse influence of the bite mark in food, under room temperature conditions, was also examined. For the documentation of the bite marks and the dentitions of the biters, 3D optical surface scanning technology was used. The comparison was performed using two different software packages: the ATOS modelling and analysing software and the 3D studio max animation software. The ATOS software enables an automatic computation of the deviation between the two meshes. In the present study, the bite marks and the dentitions were compared, as well as the meshes of each bite mark which were recorded in the different stages of time lapse. In the 3D studio max software, the act of biting was animated to compare the dentitions with the bite mark. The examined food recorded the individual characteristics of the dentitions very well. In all cases, the biter could be identified, and the dentitions of the other presumed biters could be excluded. The influence of the time lapse on the food depends on the kind of food and is shown on the diagrams. However, the identification of the biter could still be performed after a period of time, based on the recorded individual characteristics of the dentitions.

A comparison of ROC inferred from FROC and conventional ROC

NASA Astrophysics Data System (ADS)

McEntee, Mark F.; Littlefair, Stephen; Pietrzyk, Mariusz W.

2014-03-01

This study aims to determine whether receiver operating characteristic (ROC) scores inferred from free-response receiver operating characteristic (FROC) were equivalent to conventional ROC scores for the same readers and cases. Forty-five examining radiologists of the American Board of Radiology independently reviewed 47 PA chest radiographs under at least two conditions. Thirty-seven cases had abnormal findings and 10 cases had normal findings. Half the readers were asked to first locate any visualized lung nodules, mark them and assign a level of confidence [the FROC mark-rating pair] and second give an overall to the entire image on the same scale [the ROC score]. The second half of readers gave the ROC rating first followed by the FROC mark-rating pairs. A normal image was represented with number 1 and malignant lesions with numbers 2-5. A jackknife free-response receiver operating characteristic (JAFROC), and inferred ROC (infROC) was calculated from the mark-rating pairs using JAFROC V4.1 software. ROC based on the overall rating of the image calculated using DBM MRMC software, which was also used to compare infROC and ROC AUCs treating the methods as modalities. Pearson's correlations coefficient and linear regression were used to examine their relationship using SPSS, version 21.0; (SPSS, Chicago, IL). The results of this study showed no significant difference between the ROC and Inferred ROC AUCs (p≤0.25). While Pearson's correlation coefficient was 0.7 (p≤0.01). Inter-reader correlation calculated from Obuchowski- Rockette covariance's ranged from 0.43-0.86 while intra-reader agreement was greater than previously reported ranging from 0.68-0.82.

5,7-Dimethoxycoumarin prevents chronic mild stress induced depression in rats through increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

PubMed

Yang, Wei; Wang, Huanlin

2018-02-01

The current study was aimed to investigate the role of 5,7-dimethoxycoumarin in the prevention of chronic mild stress induced depression in rats. The chronic mild stress rat model was prepared using the known protocols. The results from open-field test showed that rats in the chronic mild stress group scored very low in terms of crossings and rearings than those of the normal rats. However, pre-treatment of the rats with 10 mg/kg doses of 5,7-dimethoxycoumarin prevented decline in the locomotor activity by chronic mild stress. The level of monoamine oxidase-A in the chronic mild stress rat hippocampus was markedly higher. Chronic mild stress induced increase in the monoamine oxidase-A level was inhibited by pre-treatment with 10 mg/kg doses of 5,7-dimethoxycoumarin in the rats. Chronic mild stress caused a marked increase in the level of caspase-3 mRNA and proteins in rat hippocampus tissues. The increased level of caspase-3 mRNA and protein level was inhibited by treatment of rats with 5,7-dimethoxycoumarin (10 mg/kg). 5,7-Dimethoxycoumarin administration into the rats caused a marked increase in the levels of heat shock protein-70 mRNA and protein. The levels of heat shock protein-70 were markedly lower both in normal and chronic mild stress groups of rats compared to the 5,7-dimethoxycoumarin treated groups. Thus 5,7-dimethoxycoumarin prevented the chronic mild stress induced depression in rats through an increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

Multi-frequency time-difference complex conductivity imaging of canine and human lungs using the KHU Mark1 EIT system.

PubMed

Kuen, Jihyeon; Woo, Eung Je; Seo, Jin Keun

2009-06-01

We evaluated the performance of the lately developed electrical impedance tomography (EIT) system KHU Mark1 through time-difference imaging experiments of canine and human lungs. We derived a multi-frequency time-difference EIT (mftdEIT) image reconstruction algorithm based on the concept of the equivalent homogeneous complex conductivity. Imaging experiments were carried out at three different frequencies of 10, 50 and 100 kHz with three different postures of right lateral, sitting (or prone) and left lateral positions. For three normal canine subjects, we controlled the ventilation using a ventilator at three tidal volumes of 100, 150 and 200 ml. Three human subjects were asked to breath spontaneously at a normal tidal volume. Real- and imaginary-part images of the canine and human lungs were reconstructed at three frequencies and three postures. Images showed different stages of breathing cycles and we could interpret them based on the understanding of the proposed mftdEIT image reconstruction algorithm. Time series of images were further analyzed by using the functional EIT (fEIT) method. Images of human subjects showed the gravity effect on air distribution in two lungs. In the canine subjects, the morphological change seems to dominate the gravity effect. We could also observe that two different types of ventilation should have affected the results. The KHU Mark1 EIT system is expected to provide reliable mftdEIT images of the human lungs. In terms of the image reconstruction algorithm, it would be worthwhile including the effects of three-dimensional current flows inside the human thorax. We suggest clinical trials of the KHU Mark1 for pulmonary applications.

Using Correlative Properties of Neighboring Pixels to Enhance Contrast-to-Noise Ratio of Abnormal Hippocampus in Patients With Intractable Epilepsy and Mesial Temporal Sclerosis.

PubMed

Parsons, Matthew S; Sharma, Aseem; Hildebolt, Charles

2018-06-12

To test whether an image-processing algorithm can aid in visualization of mesial temporal sclerosis on magnetic resonance imaging by selectively increasing contrast-to-noise ratio (CNR) between abnormal hippocampus and normal brain. In this Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, baseline coronal fluid-attenuated inversion recovery images of 18 adults (10 females, eight males; mean age 41.2 years) with proven mesial temporal sclerosis were processed using a custom algorithm to produce corresponding enhanced images. Average (Hmean) and maximum (Hmax) CNR for abnormal hippocampus were calculated relative to normal ipsilateral white matter. CNR values for normal gray matter (GM) were similarly calculated using ipsilateral cingulate gyrus as the internal control. To evaluate effect of image processing on visual conspicuity of hippocampal signal alteration, a neuroradiologist masked to the side of hippocampal abnormality rated signal intensity (SI) of hippocampi on baseline and enhanced images using a five-point scale (definitely abnormal to definitely normal). Differences in Hmean, Hmax, GM, and SI ratings for abnormal hippocampi on baseline and enhanced images were assessed for statistical significance. Both Hmean and Hmax were significantly higher in enhanced images as compared to baseline images (p < 0.0001 for both). There was no significant difference in the GM between baseline and enhanced images (p = 0.9375). SI ratings showed a more confident identification of abnormality on enhanced images (p = 0.0001). Image-processing resulted in increased CNR of abnormal hippocampus without affecting the CNR of normal gray matter. This selective increase in conspicuity of abnormal hippocampus was associated with more confident identification of hippocampal signal alteration. Copyright © 2018 Academic Radiology. Published by Elsevier Inc. All rights reserved.

Speckle-Tracking Echocardiography in Dogs With Patent Ductus Arteriosus: Effect of Percutaneous Closure on Cardiac Mechanics.

PubMed

Spalla, I; Locatelli, C; Zanaboni, A M; Brambilla, P; Bussadori, C

2016-05-01

Patent ductus arteriosus (PDA) is 1 of the most common congenital heart defects in dogs and percutaneous closure is effective in achieving ductal closure; PDA closure is associated with abrupt hemodynamic changes. A marked decrease in standard parameters of systolic function as assessed by M- or B-mode echocardiography after PDA closure was identified in previous studies. Speckle tracking echocardiography can provide further insight into the effect of PDA closure on cardiac mechanics in dogs affected by PDA. Twenty-five client-owned dogs with PDA. Prospective study. Dogs were recruited over a 2-year period. Complete echocardiographic evaluation was performed before and 24 hours after PDA closure, including standard (end-diastolic volumes indexed to body surface area in B- and M-mode [EDVIB /M ], end-systolic volumes indexed to body surface area in B- and M-mode [ESVIB /M ], allometric scaling in diastole [AlloD] and systole [AlloS], pulmonary flow to systemic flow [Qs/Qp], ejection fraction [EF], and fractional shortening [FS]), and advanced speckle-tracking echocardiography (STE): global longitudinal, radial, circumferential and transverse strain (S), and strain rate (SR). Patent ductus arteriosus closure was associated with statistically significant decreases in EDVIM /B and ESVIM /B , AlloD and AlloS, SI, EF, and FS. A statistically significant decrease in the absolute values of radial, transverse, and circumferential S and SR was observed, whereas longitudinal S and SR did not change significantly. Patent ductus arteriosus closure by percutaneous approach is associated with marked decreases of conventional echocardiographic parameters as a result of the changes in loading conditions, but no evidence of systolic dysfunction was identified by means of STE, as none of the S and SR values were below reference ranges. In the short term, contractility is enhanced in the long axis (long S/SR values were not statistically different before and after closure) and decreases to normal values in short axis (circumferential, radial, and transversal S/SR decreased to normal reference range). Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Ultracentrifugal and electrophoretic characteristics of the plasma lipoproteins of miniature schnauzer dogs with idiopathic hyperlipoproteinemia.

PubMed

Whitney, M S; Boon, G D; Rebar, A H; Story, J A; Bottoms, G D

1993-01-01

To better characterize the idiopathic hyperlipoproteinemia of Miniature Schnauzer dogs, the plasma lipoproteins of 20 Miniature Schnauzers (MS) and 11 dogs of other breeds (DOB) were evaluated by ultracentrifugation, electrophoresis, and biochemical tests. Seventeen MS were healthy; 3 had diabetes mellitus. Plasma from 6 of 17 healthy and all 3 diabetic MS was visibly lipemic. Lipemia was slight to marked in healthy lipemic MS, and marked in diabetic ones. All DOB had clear plasma; 8 were healthy and 3 had diabetes. All healthy lipemic MS and diabetic lipemic MS had hypertriglyceridemia associated with excess very low density lipoproteins. Chylomicronemia was present in 4 of 6 healthy lipemic MS and all 3 diabetic lipemic MS. Lipoproteins with ultracentrifugal and electrophoretic characteristics of normal low density lipoprotein were lacking in 4 of 6 healthy lipemic MS. The lipoprotein patterns of 4 of 11 healthy nonlipemic MS were characterized by mild hypertriglyceridemia associated with increased very low density lipoproteins and a lack of lipoproteins with characteristics of normal low density lipoproteins. Lipoprotein patterns of diabetic DOB closely resembled those of healthy DOB; those of diabetic lipemic MS resembled those of markedly lipemic healthy lipemic MS. In conclusion, the hyperlipoproteinemia of Miniature Schnauzers is characterized by increased very low density lipoproteins with or without accompanying chylomicronemia; some affected dogs may have decreased low density lipoproteins.

Enhancement pattern of the normal facial nerve at 3.0 T temporal MRI.

PubMed

Hong, H S; Yi, B-H; Cha, J-G; Park, S-J; Kim, D H; Lee, H K; Lee, J-D

2010-02-01

The purpose of this study was to evaluate the enhancement pattern of the normal facial nerve at 3.0 T temporal MRI. We reviewed the medical records of 20 patients and evaluated 40 clinically normal facial nerves demonstrated by 3.0 T temporal MRI. The grade of enhancement of the facial nerve was visually scaled from 0 to 3. The patients comprised 11 men and 9 women, and the mean age was 39.7 years. The reasons for the MRI were sudden hearing loss (11 patients), Méniàre's disease (6) and tinnitus (7). Temporal MR scans were obtained by fluid-attenuated inversion-recovery (FLAIR) and diffusion-weighted imaging of the brain; three-dimensional (3D) fast imaging employing steady-state acquisition (FIESTA) images of the temporal bone with a 0.77 mm thickness, and pre-contrast and contrast-enhanced 3D spoiled gradient record acquisition in the steady state (SPGR) of the temporal bone with a 1 mm thickness, were obtained with 3.0 T MR scanning. 40 nerves (100%) were visibly enhanced along at least one segment of the facial nerve. The enhanced segments included the geniculate ganglion (77.5%), tympanic segment (37.5%) and mastoid segment (100%). Even the facial nerve in the internal auditory canal (15%) and labyrinthine segments (5%) showed mild enhancement. The use of high-resolution, high signal-to-noise ratio (with 3 T MRI), thin-section contrast-enhanced 3D SPGR sequences showed enhancement of the normal facial nerve along the whole course of the nerve; however, only mild enhancement was observed in areas associated with acute neuritis, namely the canalicular and labyrinthine segment.

Relationship between thoracic auscultation and lung pathology detected by ultrasonography in sheep.

PubMed

Scott, Phil; Collie, Dave; McGorum, Bruce; Sargison, Neil

2010-10-01

The utility of routine auscultation to detect and characterise the nature of a range of superficial lung and pleural pathologies in domestic sheep was assessed using ultrasonographic examination to indicate and localise pathologies pre-mortem. Necropsy examination was then used to fully characterise the nature and extent of the lesions. Auscultation recordings were made from 10 normal sheep with no clinical evidence of respiratory disease and with absence of significant superficial lung pathology, which was confirmed initially by ultrasound examination and subsequently at necropsy examination. A further two sheep with endotoxaemia and 30 sheep with well-defined lung lesions were also examined. Increased audibility of normal lung sounds in 4/10 normal sheep was associated with tachypnoea as a consequence of handling and transport during hot weather and was also observed in the two sheep with endotoxaemia. Moderate to severe coarse crackles detected in all advanced cases of ovine pulmonary adenocarcinoma (n=16) were audible over an area larger than the lesion distribution identified during ultrasound examination, and confirmed later at necropsy. Auscultation did not detect abnormal sounds in any of the five sheep with focal pleural abscesses (up to 10 cm diameter). Unilateral pyothorax caused attenuation of sounds relative to the contra-lateral normal lung in all three sheep with this condition. Marked fibrinous pleurisy caused attenuation of sounds relative to normal areas of lung in six sheep. No sounds resembling the description of pleural frictions rubs were heard in the sheep with marked fibrinous pleurisy (n=6) or associated with focal pleural abscesses (n=5). Routine interpretation of auscultated sound did not allow the presence of superficial lung pathology or its distribution to be accurately defined in the respiratory diseases represented in this study. Copyright © 2009 Elsevier Ltd. All rights reserved.

Nek2A destruction marks APC/C activation at the prophase-to-prometaphase transition by spindle-checkpoint-restricted Cdc20.

PubMed

Boekhout, Michiel; Wolthuis, Rob

2015-04-15

Nek2 isoform A (Nek2A) is a presumed substrate of the anaphase-promoting complex/cyclosome containing Cdc20 (APC/C(Cdc20)). Nek2A, like cyclin A, is degraded in mitosis while the spindle checkpoint is active. Cyclin A prevents spindle checkpoint proteins from binding to Cdc20 and is recruited to the APC/C in prometaphase. We found that Nek2A and cyclin A avoid being stabilized by the spindle checkpoint in different ways. First, enhancing mitotic checkpoint complex (MCC) formation by nocodazole treatment inhibited the degradation of geminin and cyclin A, whereas Nek2A disappeared at a normal rate. Second, depleting Cdc20 effectively stabilized cyclin A but not Nek2A. Nevertheless, Nek2A destruction crucially depended on Cdc20 binding to the APC/C. Third, in contrast to cyclin A, Nek2A was recruited to the APC/C before the start of mitosis. Interestingly, the spindle checkpoint very effectively stabilized an APC/C-binding mutant of Nek2A, which required the Nek2A KEN box. Apparently, in cells, the spindle checkpoint primarily prevents Cdc20 from binding destruction motifs. Nek2A disappearance marks the prophase-to-prometaphase transition, when Cdc20, regardless of the spindle checkpoint, activates the APC/C. However, Mad2 depletion accelerated Nek2A destruction, showing that spindle checkpoint release further increases APC/C(Cdc20) catalytic activity. © 2015. Published by The Company of Biologists Ltd.

[Low-frequency vibrations of a Mg pyropheophorbide-histidine complex].

PubMed

Klevanic, A V; Shuvalov, V A

2001-01-01

The spectrum of vibrations and normal model for the Mg piropheophorbide-histidine complex was calculated using the MNDO-PM3 (MOPAC) semiempirical quantum chemical method. The delocalization index and the distribution function were introduced to describe the shape of normal vibrations. The greatest part (approximately 65%) of the low-frequency vibrations (1-400 cm-1) was shown to delocalize over both the His and Mg piropheophorbide molecules. Leu, Met, and Asp were also studied as the fifth ligand to the Mg piropheophorbide molecule. It is concluded that the fifth amino acid ligand to porphyrin molecules causes marked geometrical distortions in porphyrin, and induces a new, compared to four coordinated pigment, spectrum of normal modes.

Insulin and growth hormone secretion in the nephrotic syndrome.

PubMed

Bridgman, J F; Summerskill, J; Buckler, J M; Hellman, B; Rosen, S M

1975-01-01

Carbohydrate metabolism was studied in a series of patients with the nephrotic syndrome and compared with a similar number of normal controls. The nephrotic syndrome was associated with a smaller secretion of insulin in response to intravenous glucose and tolbutamide than occurred in normals. In the syndrom fasting serum growth hormone (G.H.) concentrations were increased and did not show the characteristic suppression after glucose administration, and the disappearance rate of glucose (k value) was lower. well marked correlation existed between serum G.H. concentrations and the total urinary protein excreted. These abnormal findings returned to normal in a patient who underwent a repeat study when the nephrotic syndrome had resolved.

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

Potashnik, G.; Yanai-Inbar, I.

The current study summarizes an 8-year reassessment of testicular function and reproductive performance in 15 workers with dibromochloropropane (DBCP)-induced azoospermia and oligozoospermia. Recovery of spermatogenesis was observed in four oligozoospermic and three azoospermic men whose plasma follicle-stimulating hormone (FSH) concentration was normal during the whole period. A marked increase in FSH and luteinizing hormone concentrations above the upper limit of normal was found in the azoospermic workers who did not recover. No significant changes in FSH concentrations were detected in both recovered and nonrecovered oligozoospermic men. Testosterone levels of all patients were normal at all times. Paternal exposure to DBCPmore » was not associated with increased risk of fetal malformations or spontaneous abortion.« less

Affect, affective disorder and schizophrenia. A neuropsychological investigation of right hemisphere function.

PubMed

David, A S; Cutting, J C

1990-04-01

Performance on a happy-sad chimeric face test was used to examine the role of right hemisphere activation in positive and negative affect, both normal and abnormal, as well as in schizophrenia. This test is known to elicit a left-sided perceptual bias in right-handed normal subjects. Happy and sad mood in normals did not influence the perceptual bias. Depression and mania were associated with reduced and increased biases respectively, while schizophrenics showed no bias to either side. Possible explanations are right hemisphere hyperfunction in mania, moderate relative hypofunction in depression, and severe relative hypofunction in schizophrenia. The marked difference between mania and schizophrenia supports distinct pathophysiologies underlying the two conditions.

VEGF preconditioning leads to stem cell remodeling and attenuates age-related decay of adult hippocampal neurogenesis

PubMed Central

Licht, Tamar; Rothe, Gadiel; Kreisel, Tirzah; Wolf, Brachi; Benny, Ofra; Rooney, Alasdair G.; ffrench-Constant, Charles; Enikolopov, Grigori; Keshet, Eli

2016-01-01

Several factors are known to enhance adult hippocampal neurogenesis but a factor capable of inducing a long-lasting neurogenic enhancement that attenuates age-related neurogenic decay has not been described. Here, we studied hippocampal neurogenesis following conditional VEGF induction in the adult brain and showed that a short episode of VEGF exposure withdrawn shortly after the generation of durable new vessels (but not under conditions where newly made vessels failed to persist) is sufficient for neurogenesis to proceed at a markedly elevated level for many months later. Continual neurogenic increase over several months was not accompanied by accelerated exhaustion of the neuronal stem cell (NSC) reserve, thereby allowing neurogenesis to proceed at a markedly elevated rate also in old mice. Neurogenic enhancement by VEGF preconditioning was, in part, attributed to rescue of age-related NSC quiescence. Remarkably, VEGF caused extensive NSC remodelling manifested in transition of the enigmatic NSC terminal arbor onto long cytoplasmic processes engaging with and spreading over even remote blood vessels, a configuration reminiscent of early postnatal “juvenile” NSCs. Together, these findings suggest that VEGF preconditioning might be harnessed for long-term neurogenic enhancement despite continued exposure to an “aged” systemic milieu. PMID:27849577

Enhancing Speech Intelligibility: Interactions among Context, Modality, Speech Style, and Masker

ERIC Educational Resources Information Center

Van Engen, Kristin J.; Phelps, Jasmine E. B.; Smiljanic, Rajka; Chandrasekaran, Bharath

2014-01-01

Purpose: The authors sought to investigate interactions among intelligibility-enhancing speech cues (i.e., semantic context, clearly produced speech, and visual information) across a range of masking conditions. Method: Sentence recognition in noise was assessed for 29 normal-hearing listeners. Testing included semantically normal and anomalous…

Role of tool marks inside spherical mitigation pit fabricated by micro-milling on repairing quality of damaged KH2PO4 crystal

PubMed Central

Chen, Ming-Jun; Cheng, Jian; Yuan, Xiao-Dong; Liao, Wei; Wang, Hai-Jun; Wang, Jing-He; Xiao, Yong; Li, Ming-Quan

2015-01-01

Repairing initial slight damage site into stable structures by engineering techniques is the leading strategy to mitigate the damage growth on large-size components used in laser-driven fusion facilities. For KH2PO4 crystals, serving as frequency converter and optoelectronic switch-Pockels cell, micro-milling has been proven the most promising method to fabricate these stable structures. However, tool marks inside repairing pit would be unavoidably introduced due to the wearing of milling cutter in actual repairing process. Here we quantitatively investigate the effect of tool marks on repairing quality of damaged crystal components by simulating its induced light intensification and testing the laser-induced damage threshold. We found that due to the formation of focusing hot spots and interference ripples, the light intensity is strongly enhanced with the presence of tool marks, especially for those on rear surfaces. Besides, the negative effect of tool marks is mark density dependent and multiple tool marks would aggravate the light intensification. Laser damage tests verified the role of tool marks as weak points, reducing the repairing quality. This work offers new criterion to comprehensively evaluate the quality of repaired optical surfaces to alleviate the bottleneck issue of low laser damage threshold for optical components in laser-driven fusion facilities. PMID:26399624

Handheld Lasers Allow Efficient Detection of Fluorescent Marked Organisms in the Field

PubMed Central

Fleischer, Shelby J.; De Moraes, Consuelo M.; Mescher, Mark C.; Tooker, John F.

2015-01-01

Marking organisms with fluorescent dyes and powders is a common technique used in ecological field studies that monitor movement of organisms to examine life history traits, behaviors, and population dynamics. External fluorescent marking is relatively inexpensive and can be readily employed to quickly mark large numbers of individuals; however, the ability to detect marked organisms in the field at night has been hampered by the limited detection distances provided by portable fluorescent ultraviolet lamps. In recent years, significant advances in LED lamp and laser technology have led to development of powerful, low-cost ultraviolet light sources. In this study, we evaluate the potential of these new technologies to improve detection of fluorescent-marked organisms in the field and to create new possibilities for tracking marked organisms in visually challenging environments such as tree canopies and aquatic habitats. Using handheld lasers, we document a method that provides a fivefold increase in detection distance over previously available technologies. This method allows easy scouting of tree canopies (from the ground), as well as shallow aquatic systems. This novel detection method for fluorescent-marked organisms thus promises to significantly enhance the use of fluorescent marking as a non-destructive technique for tracking organisms in natural environments, facilitating field studies that aim to document otherwise inaccessible aspects of the movement, behavior, and population dynamics of study organisms, including species with significant economic impacts or relevance for ecology and human health. PMID:26035303

Simulations of normal and inverse laminar diffusion flames under oxygen enhancement and gravity variation

NASA Astrophysics Data System (ADS)

Bhatia, P.; Katta, V. R.; Krishnan, S. S.; Zheng, Y.; Sunderland, P. B.; Gore, J. P.

2012-10-01

Steady-state global chemistry calculations for 20 different flames were carried out using an axisymmetric Computational Fluid Dynamics (CFD) code. Computational results for 16 flames were compared with flame images obtained at the NASA Glenn Research Center. The experimental flame data for these 16 flames were taken from Sunderland et al. [4] which included normal and inverse diffusion flames of ethane with varying oxidiser compositions (21, 30, 50, 100% O2 mole fraction in N2) stabilised on a 5.5 mm diameter burner. The test conditions of this reference resulted in highly convective inverse diffusion flames (Froude numbers of the order of 10) and buoyant normal diffusion flames (Froude numbers ∼0.1). Additionally, six flames were simulated to study the effect of oxygen enhancement on normal diffusion flames. The enhancement in oxygen resulted in increased flame temperatures and the presence of gravity led to increased gas velocities. The effect of gravity-variation and oxygen enhancement on flame shape and size of normal diffusion flames was far more pronounced than for inverse diffusion flames. For normal-diffusion flames, their flame-lengths decreased (1 to 2 times) and flames-widths increased (2 to 3 times) when going from earth-gravity to microgravity, and flame height decreased by five times when going from air to a pure oxygen environment.

Development of a mobile toolmark characterization/comparison system [Development of a mobile, automated toolmark characterization/comparison system

DOE PAGES

Chumbley, Scott; Zhang, Song; Morris, Max; ...

2016-11-16

Since the development of the striagraph, various attempts have been made to enhance forensic investigation through the use of measuring and imaging equipment. This study describes the development of a prototype system employing an easy-to-use software interface designed to provide forensic examiners with the ability to measure topography of a toolmarked surface and then conduct various comparisons using a statistical algorithm. Acquisition of the data is carried out using a portable 3D optical profilometer, and comparison of the resulting data files is made using software named “MANTIS” (Mark and Tool Inspection Suite). The system has been tested on laboratory-produced markingsmore » that include fully striated marks (e.g., screwdriver markings), quasistriated markings produced by shear-cut pliers, impression marks left by chisels, rifling marks on bullets, and cut marks produced by knives. Using the system, an examiner has the potential to (i) visually compare two toolmarked surfaces in a manner similar to a comparison microscope and (ii) use the quantitative information embedded within the acquired data to obtain an objective statistical comparison of the data files. Finally, this study shows that, based on the results from laboratory samples, the system has great potential for aiding examiners in conducting comparisons of toolmarks.« less

Development of a mobile toolmark characterization/comparison system [Development of a mobile, automated toolmark characterization/comparison system

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

Chumbley, Scott; Zhang, Song; Morris, Max

Since the development of the striagraph, various attempts have been made to enhance forensic investigation through the use of measuring and imaging equipment. This study describes the development of a prototype system employing an easy-to-use software interface designed to provide forensic examiners with the ability to measure topography of a toolmarked surface and then conduct various comparisons using a statistical algorithm. Acquisition of the data is carried out using a portable 3D optical profilometer, and comparison of the resulting data files is made using software named “MANTIS” (Mark and Tool Inspection Suite). The system has been tested on laboratory-produced markingsmore » that include fully striated marks (e.g., screwdriver markings), quasistriated markings produced by shear-cut pliers, impression marks left by chisels, rifling marks on bullets, and cut marks produced by knives. Using the system, an examiner has the potential to (i) visually compare two toolmarked surfaces in a manner similar to a comparison microscope and (ii) use the quantitative information embedded within the acquired data to obtain an objective statistical comparison of the data files. Finally, this study shows that, based on the results from laboratory samples, the system has great potential for aiding examiners in conducting comparisons of toolmarks.« less

Front lighted optical tooling method and apparatus

DOEpatents

Stone, W.J.

1983-06-30

An optical tooling method and apparatus uses a front lighted shadowgraphic technique to enhance visual contrast of reflected light. The apparatus includes an optical assembly including a fiducial mark, such as cross hairs, reflecting polarized light with a first polarization, a polarizing element backing the fiducial mark and a reflective surface backing the polarizing element for reflecting polarized light bypassing the fiducial mark and traveling through the polarizing element. The light reflected by the reflecting surface is directed through a second pass of the polarizing element toward the frontal direction with a polarization differing from the polarization of the light reflected by the fiducial mark. When used as a tooling target, the optical assembly may be mounted directly to a reference surface or may be secured in a mounting, such as a magnetic mounting. The optical assembly may also be mounted in a plane defining structure and used as a spherometer in conjunction with an optical depth measuring instrument.

Increased expression of the interleukin 1 receptor on blood neutrophils of humans with the sepsis syndrome.

PubMed Central

Fasano, M B; Cousart, S; Neal, S; McCall, C E

1991-01-01

Because of the potential importance of interleukin 1 (IL-1) in modulating inflammation and the observations that human blood neutrophils (PMN) express IL-1 receptors (IL-1R) and synthesize IL-1 alpha and IL-1 beta, we studied the IL-1R on blood PMN from a group of patients with the sepsis syndrome. We report a marked enhancement in the sites per cell of IL-1R expressed on sepsis-PMN of 25 consecutively studied patients compared to 20 controls (patient mean = 9,329 +/- 2,212 SE; control mean = 716 +/- 42 SE, respectively). There was no demonstrable difference in the Kd of IL-1R on sepsis-PMN (approximately 1 nM) as determined by saturation curves of 125I-IL-1 alpha binding and the IL-1R on sepsis-PMN had an apparent Mr approximately 68,000, a value like that of normal PMN. Cytofluorographic analysis indicated that the sepsis-PMN phenotype is a single homogeneous population with respect to IL-1R expression. In contrast, expression of the membrane complement receptor CR3 is not increased on sepsis-PMN. Similar increases in expression of IL-1R were not observed in various other inflammatory processes, including acute disseminated inflammation and organ failure not caused by infection, acute infection without organ failure, and immunopathologies such as active systemic lupus erythematosus and rheumatoid arthritis. Enhanced expression of IL-1R was not related simply to the state of myeloid stimulation. Increased expression of IL-1R on normal PMN was induced in vitro by incubating cells with recombinant human granulocyte-macrophage/colony-stimulating factor for 18 h and this response was inhibited by cycloheximide, suggesting the possibility that de novo synthesis of IL-1R might occur in PMN during the sepsis syndrome. Images PMID:1834697

Production of interleukin (IL)-5 and IL-10 accompanies T helper cell type 1 (Th1) cytokine responses to a major thyroid self-antigen, thyroglobulin, in health and autoimmune thyroid disease

PubMed Central

Nielsen, C H; Hegedüs, L; Rieneck, K; Moeller, A C; Leslie, R G Q; Bendtzen, K

2007-01-01

Tumour necrosis factor (TNF)-α and interferon (IFN)-γ exert detrimental effects in organ-specific autoimmune disease, while both destructive and protective roles have been demonstrated for interleukin (IL)-10, IL-4 and IL-5. We examined the production of these cytokines by peripheral blood mononuclear cells (PBMC) from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD) and healthy controls, upon exposure to a thyroid self-antigen, human thyroglobulin (Tg), in the presence of autologous serum. Initially, TNF-α and IL-2 were produced in all three groups, accompanied by IL-10. Release of IFN-γ, IL-4 and, notably, IL-5 ensued. Both patient groups exhibited increased TNF-α, IL-2, IFN-γ and IL-10 responses, and PBMC from HT patients secreted lower amounts of IL-5 than male, but not female, controls. Enhanced TNF-α production by HT cells also occurred in the presence of pooled normal sera, indicating a dependency on intrinsic cellular factors. Conversely, higher production of TNF-α and IL-5 occurred in the presence of autologous sera than in the presence of pooled normal sera in both patient groups, indicating a dependency on serum constituents. Complement appeared to promote the production of IL-2 and particularly IL-5, the levels of which were reduced by neutralization of complement by heat- or zymosan treatment. The production of IFN-γ and IL-2 of the three groups together correlated directly with the serum anti-Tg activity. Moreover, TNF-α, IFN-γ, IL-5 and IL-10 responses were markedly inhibited by partial denaturation of Tg by boiling. We hypothesize that autoantibodies and complement may promote mixed Th1/Th2 cell cytokine responses by enhancing the uptake of autoantigens by antigen-presenting cells. PMID:17223970

Bcl-2 silencing attenuates hypoxia-induced apoptosis resistance in pulmonary microvascular endothelial cells.

PubMed

Cao, Yongmei; Jiang, Zhen; Zeng, Zhen; Liu, Yujing; Gu, Yuchun; Ji, Yingying; Zhao, Yupeng; Li, Yingchuan

2016-01-01

Pulmonary arterial hypertension (PAH) is a life-threatening disorder that ultimately causes heart failure. While the underlying causes of this condition are not well understood, previous studies suggest that the anti-apoptotic nature of pulmonary microvascular endothelial cells (PMVECs) in hypoxic environments contributes to PAH pathogenesis. In this study, we focus on the contribution of Bcl-2 and hypoxia response element (HRE) to apoptosis-resistant endothelial cells and investigate the mechanism. PMVECs obtained from either normal rats or apoptosis-resistant PMVECs obtained from PAH rats were transduced with recombinant lentiviral vectors carrying either Bcl-2-shRNA or HRE combined Bcl-2-shRNA, and then cultured these cells for 24 h under hypoxic (5% O2) or normoxic (21% O2) conditions. In normal PMVECs, Bcl-2-shRNA or HRE combined with Bcl-2-shRNA transduction successfully decreased Bcl-2 expression, while increasing apoptosis as well as caspase-3 and P53 expression in a normoxic environment. In a hypoxic environment, the effects of Bcl-2-shRNA treatment on cell apoptosis, and on Bcl-2, caspase-3, P53 expression were significantly suppressed. Conversely, HRE activation combined with Bcl-2-shRNA transduction markedly enhanced cell apoptosis and upregulated caspase-3 and P53 expression, while decreasing Bcl-2 expression. Furthermore, in apoptosis-resistant PMVECs, HRE-mediated Bcl-2 silencing effectively enhanced cell apoptosis and caspase-3 activity. The apoptosis rate was significantly depressed when Lv-HRE-Bcl-2-shRNA was combined with Lv-P53-shRNA or Lv-caspase3-shRNA transduction in a hypoxic environment. These results suggest that HRE-mediated Bcl-2 inhibition can effectively attenuate hypoxia-induced apoptosis resistance in PMVECs by downregulating Bcl-2 expression and upregulating caspase-3 and P53 expression. This study therefore reveals critical insight into potential therapeutic targets for treating PAH.

The fracture criticality of crustal rocks

NASA Astrophysics Data System (ADS)

Crampin, Stuart

1994-08-01

The shear-wave splitting observed along almost all shear-wave ray paths in the Earth's crust is interpreted as the effects of stress-aligned fluid-filled cracks, microcracks, and preferentially oriented pore space. Once away from the free surface, where open joints and fractures may lead to strong anisotropy of 10 per cent or greater, intact ostensibly unfractured crustal rock exhibits a limited range of shear-wave splitting from about 1.5 to 4.5 per cent differential shear-wave velocity anisotropy. Interpreting this velocity anisotropy as normalized crack densities, a factor of less than two in crack radius covers the range from the minimum 1.5 per cent anisotropy observed in intact rock to the 10 per cent observed in heavily cracked almost disaggregated near-surface rocks. This narrow range of crack dimensions and the pronounced effect on rock cohesion suggests that there is a state of fracture criticality at some level of anisotropy between 4.5 and 10 per cent marking the boundary between essentially intact, and heavily fractured rock. When the level of fracture criticality is exceeded, cracking is so severe that there is a breakdown in shear strength, the likelihood of progressive fracturing and the dispersal of pore fluids through enhanced permeability. The range of normalized crack dimensions below fracture criticality is so small in intact rock, that any modification to the crack geometry by even minor changes of conditions or minor deformation (particularly in the presence of high pore-fluid pressures) may change rock from being essentially intact (below fracture criticality) to heavily fractured (above fracture criticality). This recognition of the essential compliance of most crustal rocks, and its effect on shear-wave splitting, has implications for monitoring changes in any conditions affecting the rock mass. These include monitoring changes in reservoir evolution during hydrocarbon production and enhanced oil recovery, and in monitoring changes before and after earthquakes, amongst others.

Impaired Ca2+ cycling of nonischemic myocytes contributes to sarcomere dysfunction early after myocardial infarction.

PubMed

Kronenbitter, Annette; Funk, Florian; Hackert, Katarzyna; Gorreßen, Simone; Glaser, Dennis; Boknik, Peter; Poschmann, Gereon; Stühler, Kai; Isić, Malgorzata; Krüger, Martina; Schmitt, Joachim P

2018-06-01

Changes in the nonischemic remote myocardium of the heart contribute to left ventricular dysfunction after ischemia and reperfusion (I/R). Understanding the underlying mechanisms early after I/R is crucial to improve the adaptation of the viable myocardium to increased mechanical demands. Here, we investigated the role of myocyte Ca 2+ handling in the remote myocardium 24 h after 60 min LAD occlusion. Cardiomyocytes isolated from the basal noninfarct-related parts of wild type mouse hearts demonstrated depressed beat-to-beat Ca 2+ handling. The amplitude of the Ca 2+ transients as well as the kinetics of Ca 2+ transport were reduced by up to 25%. These changes were associated with impaired sarcomere contraction. While expression levels of Ca 2+ regulatory proteins were unchanged in remote myocardium compared to the corresponding regions of sham-operated hearts, mobility shift analyses of phosphorylated protein showed 2.9 ± 0.4-fold more unphosphorylated phospholamban (PLN) monomers, the PLN species that inhibits the Ca 2+ ATPase SERCA2a (P ≤ 0.001). Phospho-specific antibodies revealed normal phosphorylation of PLN at T17 in remote myocardium, but markedly reduced phosphorylation at its PKA-dependent phosphorylation site, S16 (P ≤ 0.01). The underlying cause involved enhanced activity of protein phosphatases, particularly PP2A (P ≤ 0.01). In contrast, overall PKA activity was normal. The PLN interactome, as determined by co-immunoprecipitation and mass spectrometry, and the phosphorylation state of PKA targets other than PLN were also unchanged. Isoproterenol enhanced cellular Ca 2+ cycling much stronger in remote myocytes than in healthy controls and improved sarcomere function. We conclude that the reduced phosphorylation state of PLN at S16 impairs myocyte Ca 2+ cycling in the remote myocardium 24 h after I/R and contributes to contractile dysfunction. Copyright © 2018 Elsevier Ltd. All rights reserved.

Laser direct marking applied to rasterizing miniature Data Matrix Code on aluminum alloy

NASA Astrophysics Data System (ADS)

Li, Xia-Shuang; He, Wei-Ping; Lei, Lei; Wang, Jian; Guo, Gai-Fang; Zhang, Teng-Yun; Yue, Ting

2016-03-01

Precise miniaturization of 2D Data Matrix (DM) Codes on Aluminum alloy formed by raster mode laser direct part marking is demonstrated. The characteristic edge over-burn effects, which render vector mode laser direct part marking inadequate for producing precise and readable miniature codes, are minimized with raster mode laser marking. To obtain the control mechanism for the contrast and print growth of miniature DM code by raster laser marking process, the temperature field model of long pulse laser interaction with material is established. From the experimental results, laser average power and Q frequency have an important effect on the contrast and print growth of miniature DM code, and the threshold of laser average power and Q frequency for an identifiable miniature DM code are respectively 3.6 W and 110 kHz, which matches the model well within normal operating conditions. In addition, the empirical model of correlation occurring between laser marking parameters and module size is also obtained, and the optimal processing parameter values for an identifiable miniature DM code of different but certain data size are given. It is also found that an increase of the repeat scanning number effectively improves the surface finish of bore, the appearance consistency of modules, which has benefit to reading. The reading quality of miniature DM code is greatly improved using ultrasonic cleaning in water by avoiding the interference of color speckles surrounding modules.

A generalized mixed effects model of abundance for mark-resight data when sampling is without replacement

USGS Publications Warehouse

McClintock, B.T.; White, Gary C.; Burnham, K.P.; Pryde, M.A.; Thomson, David L.; Cooch, Evan G.; Conroy, Michael J.

2009-01-01

In recent years, the mark-resight method for estimating abundance when the number of marked individuals is known has become increasingly popular. By using field-readable bands that may be resighted from a distance, these techniques can be applied to many species, and are particularly useful for relatively small, closed populations. However, due to the different assumptions and general rigidity of the available estimators, researchers must often commit to a particular model without rigorous quantitative justification for model selection based on the data. Here we introduce a nonlinear logit-normal mixed effects model addressing this need for a more generalized framework. Similar to models available for mark-recapture studies, the estimator allows a wide variety of sampling conditions to be parameterized efficiently under a robust sampling design. Resighting rates may be modeled simply or with more complexity by including fixed temporal and random individual heterogeneity effects. Using information theory, the model(s) best supported by the data may be selected from the candidate models proposed. Under this generalized framework, we hope the uncertainty associated with mark-resight model selection will be reduced substantially. We compare our model to other mark-resight abundance estimators when applied to mainland New Zealand robin (Petroica australis) data recently collected in Eglinton Valley, Fiordland National Park and summarize its performance in simulation experiments.

Short children with familial short stature show enhancement of somatotroph secretion but normal IGF-I levels.

PubMed

Bellone, S; Corneli, G; Bellone, J; Baffoni, C; Rovere, S; de Sanctis, C; Bona, G; Ghigo, E; Aimaretti, G

2002-05-01

The aim of the present study was to evaluate the GH status in children with familial, idiopathic short stature (FSS). To this goal we evaluated the GH response to GHRH (1 microg/kg iv) + arginine (ARG) (0.5 g/kg iv) test which is one of the most potent and reproducible provocative tests of somatotroph secretion, in 67 children with FSS [50 boys and 17 girls, age 10.8+/-0.4 yr, pubertal stages I-III, height between -3.6 and -1.6 standard deviation score (SDS), target height <10 degrees centile, normality of both spontaneous and stimulated GH secretion as well as of IGF-I levels]. The results in FSS were compared with those in groups of children of normal height (NHC) (42 NHC, 35 boys and 7 girls, age 12.0+/-0.5 yr, pubertal stages I-III, height between -1.3 and 1.4 SDS, height velocity standard deviation score (HVSDS)>25 degrees centile, GH peak >20 microg/l after GHRH+ARG test, mean GH concentration [mGHc]>3 microg/l) and children with organic GH deficiency (GHD) (38 GHD, 29 boys and 9 girls, age 11.2+/-3.7 yr, pubertal stages I-III, height between -5.7 and -1.3 SDS, GH peak <20 microg/l after GHRH +ARG test, mGHc <3 mg/l). Basal IGF-I levels and mGHc were also evaluated in each group over 8 nocturnal hours. IGF-I levels in FSS (209.2+/-15.6 microg/l) were similar to those in NHC (237.2+/-17.2 microg/l) and both were higher (p<0.0001) than those in GHD (72.0+/-4.0 microg/l). The GH response to GHRH +ARG test in FSS (peak: 66.4+/-5.6 microg/l) was very marked and higher (p<0.01) than that in NHC (53.3+/-4.5 microg/l) which, in turn, was higher (p<0.01) than in GHD (8.2+/-0.8 microg/l). Similarly, the mGHc in FSS was higher than in NHC (6.7+/-0.5 microg/l vs 5.1+/-0.7 microg/l, p<0.05) which, in turn, was higher than in GHD (1.5+/-0.2 microg/l, p<0.0001). In conclusion, our present study demonstrates that short children with FSS show enhancement of both basal and stimulated GH secretion but normal IGF-I levels. These findings suggest that increased somatotroph function would be devoted to maintain normal IGF-I levels thus reflecting a slight impairment of peripheral GH sensitivity in FSS.

[A case of lung cancer producing granulocyte colony-stimulating factor with a significantly high uptake in the bones observed by a FDG-PET scan].

PubMed

Hidaka, Dai; Koshizuka, Hiroaki; Hiyama, Junichiro; Nakatsubo, Seita; Ikeda, Koutarou; Hayashi, Akihiro; Fujii, Akiko; Sawamoto, Ryouko; Misumi, Yukihiro; Miyagawa, Yousuke

2009-03-01

A 57-year-old man complaining of right shoulder pain was admitted. Chest enhanced CT scanning showed a mass shadow in the right upper lobe with chest wall invasion. The laboratory data on admission showed marked leukocytosis. A CT-guided lung biopsy was performed, and a histological examination of the biopsy specimen showed a spindle cell type pleomorphic carcinoma. Immunohistochemistry staining using an anti-granulocyte colony-stimulating factor (G-CSF) monoclonal antibody demonstrated many tumor cells containing G-CSF as well as an increased level of serum G-CSF. The diagnosis was determined to be lung cancer producing G-CSF. FDG-PET scanning showed a significantly high uptake in the right upper field and the bones throughout the body. After chemoradiation therapy, the patient underwent a right upper lobectomy with a chest wall resection. Since then, the leukocytosis and the high level of serum G-CSF normalized and the high uptake in the bones disappeared in the FDG-PET scan.

Electron dynamics surrounding the X line in asymmetric magnetic reconnection

NASA Astrophysics Data System (ADS)

Zenitani, S.; Hasegawa, H.; Nagai, T.

2017-12-01

Electron dynamics surrounding the X line in magnetopause-type asymmetric reconnection is investigated using a two-dimensional particle-in-cell simulation. We study electron properties of three characteristic regions in the vicinity of the X line. The fluid properties, velocity distribution functions (VDFs), and orbits are studied and cross-compared. On the magnetospheric side of the X line, the normal electric field enhances the electron meandering motion from the magnetosheath side. The motion leads to a crescent-shaped component in the electron VDF, in agreement with recent studies. On the magnetosheath side of the X line, the magnetic field line is so stretched in the third dimension that its curvature radius is comparable with typical electron Larmor radius. The electron motion becomes nonadiabatic, and therefore the electron idealness is no longer expected to hold. Around the middle of the outflow regions, the electron nonidealness is coincident with the region of the nonadiabatic motion. Finally, we introduce a finite-time mixing fraction (FTMF) to evaluate electron mixing. The FTMF marks the magnetospheric side of the X line, where the nonideal energy dissipation occurs.

Stimulation of globin synthesis: relative responsiveness of reticulocytes and nucleated erythroid cells

PubMed Central

Waxman, Herbert S.

1970-01-01

The effects of iron, cobalt, hemin, and plasma on hemoglobin synthesis by suspensions of rabbit reticulocytes and nucleated bone marrow cells were studied. L-Leucine-14C and sodium pyruvate-3-14C were employed to measure globin and heme synthesis, respectively. Normal plasma (or serum) was found to stimulate the rate of globin synthesis in both systems. The stimulatory effects of iron and hemin were additive to those of plasma or serum only in the reticulocytes. Cobaltous ion, at concentrations less than 1.0 mmole/liter, was found to stimulate globin synthesis by reticulocytes as effectively as ferrous ion; cobalt was inhibitory only at concentrations greater than 3.0-5.0 mmoles/liter. Heme synthesis by reticulocytes was inhibited at all concentrations employed (0.2-5.0 mmoles/liter). In bone marrow nucleated erythroid cells, globin synthesis was markedly enhanced by exogenous hemin. In contrast to reticulocytes, however, bone marrow cells were unresponsive to either cobalt or transferrin-bound iron. Possible implications of these findings on regulation of the rate and mechanism of iron uptake and hemoglobin synthesis in vivo are discussed. PMID:5443172

The tripartite model of anxiety and depression: symptom structure in depressive and hypertensive patient groups.

PubMed

Marshall, Grant N; Sherbourne, Cathy D; Meredith, Lisa S; Camp, Patti; Hays, Ron D

2003-04-01

The structure of self-reported symptoms representative of the tripartite model was examined using data drawn from the Medical Outcomes Study (Tarlov et al., 1989). Participants were persons who had been diagnosed 48 months previously as suffering from either depression (N = 315) or hypertension (N = 403). Results of confirmatory factor analyses were broadly consistent with the tripartite model (L. A. Clark & Watson, 1991). Factors emerged corresponding to each of the 3 posited first-order dimensions of negative affect, positive affect, and physiologic arousal. Nonetheless, some discrepancies were found between the observed data and the hypothesized tripartite model. First, the obtained physiologic arousal factor was best viewed as reflecting nonspecific somatic distress rather than physiologic arousal. Finally, although differentiable in the strictest statistical sense, all three domains were significantly correlated (.36 to.86, absolute value). In particular, contrary to the tripartite model, positive and negative affect covaried markedly (-.81 to -.86). Findings raise issues concerning the utility of the tripartite model as a heuristic framework for enhancing understanding of individual differences in normal mood as well as mood disorders.

Identification of the TaBTF3 gene in wheat (Triticum aestivum L.) and the effect of its silencing on wheat chloroplast, mitochondria and mesophyll cell development.

PubMed

Ma, Hong-Zhen; Liu, Guo-Qin; Li, Cheng-Wei; Kang, Guo-Zhang; Guo, Tian-Cai

2012-10-05

The full-length cDNA (882bp) and DNA (1742bp) sequences encoding a basic transcription factor 3, designated as TaBTF3, were first isolated from common wheat (Triticum aestivum L.). Subcellular localization studies revealed that the TaBTF3 protein was mainly located in the cytoplasm and nucleus. In TaBTF3-silenced transgenic wheat seedlings obtained using the Virus-induced gene silencing (VIGS) method, the chlorophyll pigment content was markedly reduced. However, the malonaldehyde (MDA) and H(2)O(2) contents were enhanced, and the structure of the wheat mesophyll cell was seriously damaged. Furthermore, transcripts of the chloroplast- and mitochondrial-encoded genes were significantly reduced in TaBTF3-silenced transgenic wheat plants. These results suggest that the TaBTF3 gene might function in the development of the wheat chloroplast, mitochondria and mesophyll cell. This paper is the first report to describe the involvement of TaBTF3 in maintaining the normal plant mesophyll cell structure. Copyright © 2012 Elsevier Inc. All rights reserved.

Stem Cell Antigen-1 Deficiency Enhances the Chemopreventive Effect of Peroxisome Proliferator-Activated Receptorγ Activation

PubMed Central

Yuan, Hongyan; Upadhyay, Geeta; Yin, Yuzhi; Kopelovich, Levy; Glazer, Robert I.

2011-01-01

Stem cell antigen-1 (Sca-1, Ly6A) is a glycerophosphatidylinositol (GPI)-anchored protein that was identified as a murine marker of bone marrow stem cells. Although Sca-1 is widely used to enrich for stem and progenitor cells in various tissues, little is known about its function and associated signaling pathways in normal and malignant cells. Here, we report that the absence of Sca-1 in the mammary gland resulted in higher levels of PPARγ and PTEN, and a reduction of pSer84PPARγ, pERK1/2 and PPARδ. This phenotype correlated with markedly increased sensitivity of Sca-1 null mice to PPARγ agonist GW7845 and insensitivity to PPARδ agonist GW501516. Reduction of Sca-1 expression in mammary tumor cells by RNA interference resulted in a phenotype similar to the Sca-1 deficient mammary gland, as evidenced by increased PPARγ expression and transcriptional activity, resulting in part from a lesser susceptibility to proteasomal degradation. These data implicate Sca-1 as a negative regulator of the tumor suppressor effects of PPARγ. PMID:21955520

Effects of different transferrin forms on transferrin receptor expression, iron uptake, and cellular proliferation of human leukemic HL60 cells. Mechanisms responsible for the specific cytotoxicity of transferrin-gallium.

PubMed Central

Chitambar, C R; Seligman, P A

1986-01-01

We have previously shown that human leukemic cells proliferate normally in serum-free media containing various transferrin forms, but the addition of transferrin-gallium leads to inhibition of cellular proliferation. Because gallium has therapeutic potential, the effects of transferrin-gallium on leukemic cell proliferation, transferrin receptor expression, and cellular iron utilization were studied. The cytotoxicity of gallium is considerably enhanced by its binding to transferrin and cytotoxicity can be reversed by transferrin-iron but not by other transferrin forms. Exposure to transferrin-gallium leads to a marked increase in cell surface transferrin binding sites, but despite this, cellular 59Fe incorporation is inappropriately low. Although shunting of transferrin-gallium to another cellular compartment has not been ruled out, other studies suggest that transferrin-gallium impairs intracellular release of 59Fe from transferrin by interfering with processes responsible for intracellular acidification. These studies, taken together, demonstrate that inhibition of cellular iron incorporation by transferrin-gallium is a prerequisite for inhibition of cellular proliferation. PMID:3465751

Incretin Receptor Null Mice Reveal Key Role of GLP-1 but Not GIP in Pancreatic Beta Cell Adaptation to Pregnancy

PubMed Central

Moffett, R. Charlotte; Vasu, Srividya; Thorens, Bernard; Drucker, Daniel J.; Flatt, Peter R.

2014-01-01

Islet adaptations to pregnancy were explored in C57BL6/J mice lacking functional receptors for glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). Pregnant wild type mice and GIPRKO mice exhibited marked increases in islet and beta cell area, numbers of medium/large sized islets, with positive effects on Ki67/Tunel ratio favouring beta cell growth and enhanced pancreatic insulin content. Alpha cell area and glucagon content were unchanged but prohormone convertases PC2 and PC1/3 together with significant amounts of GLP-1 and GIP were detected in alpha cells. Knockout of GLP-1R abolished these islet adaptations and paradoxically decreased pancreatic insulin, GLP-1 and GIP. This was associated with abolition of normal pregnancy-induced increases in plasma GIP, L-cell numbers, and intestinal GIP and GLP-1 stores. These data indicate that GLP-1 but not GIP is a key mediator of beta cell mass expansion and related adaptations in pregnancy, triggered in part by generation of intra-islet GLP-1. PMID:24927416

Oncogenic RAS pathway activation promotes resistance to anti-VEGF therapy through G-CSF–induced neutrophil recruitment

PubMed Central

Phan, Vernon T.; Wu, Xiumin; Cheng, Jason H.; Sheng, Rebecca X.; Chung, Alicia S.; Zhuang, Guanglei; Tran, Christopher; Song, Qinghua; Kowanetz, Marcin; Sambrone, Amy; Tan, Martha; Meng, Y. Gloria; Jackson, Erica L.; Peale, Franklin V.; Junttila, Melissa R.; Ferrara, Napoleone

2013-01-01

Granulocyte-colony stimulating factor (G-CSF) promotes mobilization of CD11b+Gr1+ myeloid cells and has been implicated in resistance to anti-VEGF therapy in mouse models. High G-CSF production has been associated with a poor prognosis in cancer patients. Here we show that activation of the RAS/MEK/ERK pathway regulates G-CSF expression through the Ets transcription factor. Several growth factors induced G-CSF expression by a MEK-dependent mechanism. Inhibition of G-CSF release with a MEK inhibitor markedly reduced G-CSF production in vitro and synergized with anti-VEGF antibodies to reduce CD11b+Ly6G+ neutrophil mobilization and tumor growth and led to increased survival in animal models of cancer, including a genetically engineered mouse model of pancreatic adenocarcinoma. Analysis of biopsies from pancreatic cancer patients revealed increased phospho-MEK, G-CSF, and Ets expression and enhanced neutrophil recruitment compared with normal pancreata. These results provide insights into G-CSF regulation and on the mechanism of action of MEK inhibitors and point to unique anticancer strategies. PMID:23530240

Anti-diabetic effects of the ethanol extract of a functional formula diet in mice fed with a fructose/fat-rich combination diet.

PubMed

Cheng, Qian; Zhang, Xiaofeng; Wang, Ou; Liu, Jia; Cai, Shengbao; Wang, Ruojun; Zhou, Feng; Ji, Baoping

2015-01-01

Rhizoma dioscorea, Lycium barbarum, Prunella vulgaris and hawthorn are well known in both traditional food and folk medicine. Each of these plants reportedly possesses beneficial effects in the treatment of diabetes. In this study an anti-diabetic health-promoting diet was formulated by mixing the herbs in a ratio of 6:4:2:3, and the anti-diabetic effect and underlying mechanism were elucidated in vivo. Compared with the model control group, the formula, especially its ethanol extract (EF), could improve glucose intolerance and normalize the lipid profile. The mechanisms responsible for the amelioration of glucose and lipid metabolism in mice were an increase in peripheral and hepatic insulin sensitivity, a decrease in serum free fatty acid level, enhanced hepatic glucokinase activity and glycogen content and improved serum antioxidant activity. Hepatic histopathological examination also showed that EF administration markedly decreased fatty deposits in the liver of mice. The results of the present study demonstrated that the prepared functional formula diet is a potent alternative as an anti-diabetic health-promoting diet. © 2014 Society of Chemical Industry.

A Road to Aesthetic Stylistics

ERIC Educational Resources Information Center

Al-Sheikh, Samir

2016-01-01

Being a linguistic phenomenon, poetry is marked by the defamilarization of language in a poetic discourse there is an "aesthetic distortion" of the normal codes, in which the aesthetic value is the most prominent function of the poetic texture . This study is a new adventure in correlating linguistics to aesthetics by and through the…

Minimizing morbidity of hypoglycemia in diabetes: A review of mini-dose glucagon

USDA-ARS?s Scientific Manuscript database

Type 1 diabetes is a common chronic disease of childhood and one of the most difficult conditions to manage. Advances in insulin formulations and insulin delivery devices have markedly improved the ability to achieve normal glucose homeostasis. However, hypoglycemia remains the primary limiting fact...

14 CFR 23.1567 - Flight maneuver placard.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Flight maneuver placard. 23.1567 Section 23... Information Markings and Placards § 23.1567 Flight maneuver placard. (a) For normal category airplanes, there... the approved acrobatic maneuvers and the recommended entry airspeed for each. If inverted flight...

14 CFR 23.1567 - Flight maneuver placard.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Flight maneuver placard. 23.1567 Section 23... Information Markings and Placards § 23.1567 Flight maneuver placard. (a) For normal category airplanes, there... the approved acrobatic maneuvers and the recommended entry airspeed for each. If inverted flight...

7 CFR 51.1319 - Injury.

Code of Federal Regulations, 2011 CFR

2011-01-01

... marks or other similar depressions or scars which are not very shallow or superficial, or which affect... depressions or the flesh of the pear is more than slightly affected. (4) Sunburn or sprayburn if the normal... softened or discolored. (5) More than two healed slight stings or depressions, or any stings which...

7 CFR 51.1319 - Injury.

Code of Federal Regulations, 2012 CFR

2012-01-01

... marks or other similar depressions or scars which are not very shallow or superficial, or which affect... depressions or the flesh of the pear is more than slightly affected. (4) Sunburn or sprayburn if the normal... softened or discolored. (5) More than two healed slight stings or depressions, or any stings which...

7 CFR 51.1319 - Injury.

Code of Federal Regulations, 2010 CFR

2010-01-01

... marks or other similar depressions or scars which are not very shallow or superficial, or which affect... depressions or the flesh of the pear is more than slightly affected. (4) Sunburn or sprayburn if the normal... softened or discolored. (5) More than two healed slight stings or depressions, or any stings which...

Enhancement of image contrast by fluorescence in microtechnology

NASA Astrophysics Data System (ADS)

Berndt, Michael; Tutsch, Rainer

2005-06-01

New developments in production technology increasingly focus on hybrid microsystems. Especially for systems with movable components, the process step of assembly is mandatory. In general, the accuracy of positioning of the parts has to be better than 1 μm. This makes specialized and automated production equipment necessary, which can lead to a conflict with the aim of flexibility of the range of products. Design for manufacturing is a well known remedy. Assembly aids are common practice today. These features of the workpieces bear no functionality for the end product but considerably ease certain process steps. By standardization of assembly aids generalized production equipment free from product-specific features could be developed. In our contribution, we demonstrate the photogrammetric determination of the positions of workpieces without reference to their exterior shape, using circular fiducial marks of 150 μm in diameter. The surface properties of the workpieces, however, still have an influence on image formation. As an example, the marks may be hidden by local specular reflections. A solution to this problem is to add an exclusive optical property to the fiducial marks to get an image with high contrast against the surface of the workpiece. In biology and medicine samples are stained with fluorescing dyes to enhance the contrast in optical microscopy. In fluorochromes, light of a characteristic wavelength is emitted after the absorption of light with a shorter wavelength. In our experiments we added a fluorochrome to a common photoresist and coated the surface of the workpiece with a thin layer thereof. Using photolithography as a patterning technique we generated fiducial marks with structures down to 25 μm. These marks can be identified by their characteristic emission wavelength under short-wavelength illumination. Only the fiducial marks remain visible in the images and processing these images is straightforward. The generation of fluorescing patterns by photolithography opens new possibilities for testing and process control in many fields of microtechnology.

Hyperestrogenemia and presence of estrogen receptors associated with an epithelial ovarian tumor of low malignant potential.

PubMed

Ben-Hur, H; Dgani, R; Insler, V; Lifschitz-Mercer, B; Blickstein, I; Mor, G; Kohen, F; Shani, A; Biran, H

1996-01-01

An 80-year-old woman presented with breast congestion, tenderness and pain. Mammography was normal. Circulating estradiol was markedly elevated, while LH and FSH were low. Pelvic examination and imaging revealed an ovarian mass which was extirpated during total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathology revealed an ovarian mucinous cystadenocarcinoma of low malignant potential, stage 1. The tumor was positively stained for estrogen receptors. Estradiol levels returned to normal post-operatively, with a corresponding adjustment of LH/FSH. Possible autocrine steroid production is discussed.

LECITHINASE AND LYSOLECITHINASE ACTIVITY OF RAT INTESTINAL MUCOSA AFTER WHOLE-BODY X-IRRADIATION

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

Ottolenghi, A.; Bernheim, F.

1961-11-01

Twenty-four hours after whole-body x irradiation the lecithinase activity of rat intestinal mucosa has markedly decreased and the lysolecithinase activity has decreasecp to a lesser extent. Addition of normal mucosa or chyi'otrypsin to the irradiated mucosa restores the activity of both enzymes. This indicates that irradiation eithei produces an inhibitor or inactivates a mechanism necessarly to convert pro-enzymes into active enzymes. Since chymo trypsin can increase to some extent the activity of the enzymes in normal mucosa, the second possibility seems more probable. (auth)

Computed tomography of the azygo-oesophageal recess. Normal appearances.

PubMed

Lund, G; Lien, H H

1982-01-01

Computed tomography of the azygo--oesophageal recess was performed in 85 normal subjects. The recess was convex towards the left or had an approximately straight left wall. Convexity towards the right did not occur. Localized bulges caused by the azygos vein, oesophagus and aorta were frequent. The recess became gradually deeper caudally in patients below 50 years of age. Above that age a marked posterior extension of the heart and a prevertebral position of the aorta often caused a localized shallowing at the level of the inferior pulmonary veins or the ventricles.

Normal and Oblique Impact of Cylindro-Conical and Cylindrical Projectiles on Metallic Plates

DTIC Science & Technology

1985-06-01

light grid for projcrtile rpcovery, and a witness paper marked initially at the extension of the barrel centerline placed on the front of the catcher...transducer were obtained for experimer-ti -iv’. lving normal impact on 3.175-mm-thick 2024-0 aluminum tatctýs &truck at and just above the ballistic limit...spite of the presence at its rear of a plastic gas check. These particles also prevented the use of a fine copper-wire grid conducting a current whose

Markedly accelerated catabolism of apolipoprotein A-II (ApoA-II) and high density lipoproteins containing ApoA-II in classic lecithin: cholesterol acyltransferase deficiency and fish-eye disease.

PubMed Central

Rader, D J; Ikewaki, K; Duverger, N; Schmidt, H; Pritchard, H; Frohlich, J; Clerc, M; Dumon, M F; Fairwell, T; Zech, L

1994-01-01

Classic (complete) lecithin:cholesterol acyltransferase (LCAT) deficiency and Fish-eye disease (partial LCAT deficiency) are genetic syndromes associated with markedly decreased plasma levels of high density lipoprotein (HDL) cholesterol but not with an increased risk of atherosclerotic cardiovascular disease. We investigated the metabolism of the HDL apolipoproteins (apo) apoA-I and apoA-II in a total of five patients with LCAT deficiency, one with classic LCAT deficiency and four with Fish-eye disease. Plasma levels of apoA-II were decreased to a proportionately greater extent (23% of normal) than apoA-I (30% of normal). In addition, plasma concentrations of HDL particles containing both apoA-I and apoA-II (LpA-I:A-II) were much lower (18% of normal) than those of particles containing only apoA-I (LpA-I) (51% of normal). The metabolic basis for the low levels of apoA-II and LpA-I:A-II was investigated in all five patients using both exogenous radiotracer and endogenous stable isotope labeling techniques. The mean plasma residence time of apoA-I was decreased at 2.08 +/- 0.27 d (controls 4.74 +/- 0.65 days); however, the residence time of apoA-II was even shorter at 1.66 +/- 0.24 d (controls 5.25 +/- 0.61 d). In addition, the catabolism of apoA-I in LpA-I:A-II was substantially faster than that of apoA-I in LpA-I. In summary, genetic syndromes of either complete or partial LCAT deficiency result in low levels of HDL through preferential hypercatabolism of apoA-II and HDL particles containing apoA-II. Because LpA-I has been proposed to be more protective than LpA-I:A-II against atherosclerosis, this selective effect on the metabolism of LpA-I:A-II may provide a potential explanation why patients with classic LCAT deficiency and Fish-eye disease are not at increased risk for premature atherosclerosis despite markedly decreased levels of HDL cholesterol and apoA-I. PMID:8282802

Identification of growth hormone-releasing hormone and somatostatin neurons projecting to the median eminence in normal and growth hormone-deficient Ames dwarf mice.

PubMed

Romero, M I; Phelps, C J

1997-02-01

In the spontaneous mutant Ames dwarf mouse, GH deficiency coincides with a dramatic increase in the expression of both mRNA and peptide for stimulatory GHRH and reduced expression of GH-inhibitory somatostatin (SRIH) mRNA and peptide. However, both GHRH and SRIH are markedly reduced in the dwarf median eminence (ME), suggesting that ME innervation by GHRH and SRIH neurons may be aberrant in the absence of GH. In order to test this hypothesis, the number of GHRH and SRIH ME-projecting neurons was evaluated in normal and dwarf mice using a combination of retrograde tract-tracing and neuron phenotype identification by immunocytochemistry (ICC). Adult animals were injected intraperitoneally with the fluorescent tract-tracer fluorogold (FG), which, in the brain, is taken up only by axons terminating in areas deprived of the blood-brain barrier, such as the ME. Visualization of FG was achieved by either UV illumination or ICC, and was combined as appropriate with fluorescence or bright-field ICC for GHRH or SRIH. Cells immunoreactive for GHRH or SRIH and labeled with FG were quantified at each 180-microns rostral-to-caudal level through the hypothalamus. As reported previously, the total number of hypophysiotropic GHRH neurons was markedly increased in dwarf compared with that in normal mice. However, a similar percentage of ME-innervating GHRH cells was estimated in dwarf (73 +/- 4%) and normal (76 +/- 3%) animals. Such a percentage in dwarfs thus represents a larger population of ME-projecting GHRH cells (749 +/- 53) than in normal mice (128 +/- 15). Increased numbers of FG-labeled GHRH neurons in dwarfs were located at the middle and posterior levels of the arcuate nucleus (2.08, 2.26 and 2.44 mm posterior to bregma). The percentage of FG-labeled SRIH neurons was also similar for dwarf (83 +/- 2%) and normal (87 +/- 2%) mice. Because the total SRIH-immunoreactive neuronal population in dwarfs is significantly reduced compared to that in normal animals, the similar FG-labeled percentage reflects a reduced number of SRIH cells projecting to ME in dwarf (1,376 +/- 104) compared with normal (3,192 +/- 267) mice. Fewer FG-labeled SRIH cells were found in dwarfs at every anterior-to-posterior level of the periventricular nucleus (p < 0.01 for comparisons at 0.28, 0.46, 0.64, and 1.0, and p < 0.05 for comparison at 1.18 mm posterior to the bregma). The present study indicates that the reduction in GHRH and SRIH immunoreactivity in the dwarf ME may result from different phenomena for each neuronal population. The reduction in GHRH immunostaining in the ME, despite a marked increase in the total ME-projecting GHRH neurons, may be interpreted as increased GHRH release, with consequent depletion of the ME stores. In contrast, the deficit in ME SRIH may be proportional to the deficit in the number of detectable SRIH periventricular nucleus neurons.

Monotone Increasing Binary Similarity and Its Application to Automatic Document-Acquisition of a Category

NASA Astrophysics Data System (ADS)

Suzuki, Izumi; Mikami, Yoshiki; Ohsato, Ario

A technique that acquires documents in the same category with a given short text is introduced. Regarding the given text as a training document, the system marks up the most similar document, or sufficiently similar documents, from among the document domain (or entire Web). The system then adds the marked documents to the training set to learn the set, and this process is repeated until no more documents are marked. Setting a monotone increasing property to the similarity as it learns enables the system to 1) detect the correct timing so that no more documents remain to be marked and to 2) decide the threshold value that the classifier uses. In addition, under the condition that the normalization process is limited to what term weights are divided by a p-norm of the weights, the linear classifier in which training documents are indexed in a binary manner is the only instance that satisfies the monotone increasing property. The feasibility of the proposed technique was confirmed through an examination of binary similarity and using English and German documents randomly selected from the Web.

Idiopathic granulomatous mastitis: magnetic resonance imaging findings with diffusion MRI.

PubMed

Aslan, Hulya; Pourbagher, Aysin; Colakoglu, Tamer

2016-07-01

Idiopathic granulomatous mastitis (IGM) is a rare benign breast disease with unknown etiology which can mimic breast carcinoma, both clinically and radiologically. Magnetic resonance imaging (MRI) findings of IGM have been previously described; however there is no study evaluating diffusion-weighted MRI findings of IGM. To analyze conventional, dynamic contrast-enhanced, and diffusion-weighted MRI signal characteristics of IGM by comparing it with the contralateral normal breast parenchyma. A total of 39 patients were included in the study. On dynamic contrast-enhanced MRI, the distribution and enhancement patterns of the lesions were evaluated. We also detected the frequencies of involving quadrants, retroareolar involvement, accompanying abscess, and skin edema. T2-weighted (T2W) and STIR signal intensities and both mean and minimum apparent diffusion coefficient (ADC) values were compared with the contralateral normal parenchyma. IGM showed significantly lower mean and minimum ADC values when compared with the normal parenchyma. Signal intensities on T2W and STIR sequences of the lesion were significantly higher than the normal parenchyma. On dynamic contrast-enhanced MRI, 7.7% of the patients had mass-like contrast enhancement, 92.3% of the patients had non-mass-like contrast enhancement. Abscess was positive in 33.3% of the patients. As a result, IGM showed commonly non-mass-like lesions with restricted diffusion. Although it is a benign pathology, it may show clustered ring-like enhancement like malignant lesions. © The Foundation Acta Radiologica 2015.

Self-recognition in retarded children.

PubMed

Hill, S D; Tomlin, C

1981-03-01

This study was designed to investigate the relationship between cognitive and affective development. Young preverbal retarded children watched TV images of themselves with faces marked or unmarked and of a peer whose face was marked. We used the objective technique of increased mark-directed responses as evidence of self-recognition and rated the children's reactions as they watched these images. The emergence of self-recognition was closely tied to the maturity of the children's general responsiveness to their reflections. The Down's syndrome children made a broad range of responses, including the curiosity and self-conscious behaviors characteristic of normal children during the second year of life, and all except one of these children showed evidence that they recognized their images. In contrast, the range of behaviors displayed by multihandicapped children was greatly restricted and similar to children in the first year of life. Less than half of these children showed an emergence of self-recognition.

Cognitive Enhancement and Education

ERIC Educational Resources Information Center

Buchanan, Allen

2011-01-01

Cognitive enhancement--augmenting normal cognitive capacities--is not new. Literacy, numeracy, computers, and the practices of science are all cognitive enhancements. Science is now making new cognitive enhancements possible. Biomedical cognitive enhancements (BCEs) include the administration of drugs, implants of genetically engineered or…

Leptin regulation of hippocampal synaptic function in health and disease

PubMed Central

Irving, Andrew J.; Harvey, Jenni

2014-01-01

The endocrine hormone leptin plays a key role in regulating food intake and body weight via its actions in the hypothalamus. However, leptin receptors are highly expressed in many extra-hypothalamic brain regions and evidence is growing that leptin influences many central processes including cognition. Indeed, recent studies indicate that leptin is a potential cognitive enhancer as it markedly facilitates the cellular events underlying hippocampal-dependent learning and memory, including effects on glutamate receptor trafficking, neuronal morphology and activity-dependent synaptic plasticity. However, the ability of leptin to regulate hippocampal synaptic function markedly declines with age and aberrant leptin function has been linked to neurodegenerative disorders such as Alzheimer's disease (AD). Here, we review the evidence supporting a cognitive enhancing role for the hormone leptin and discuss the therapeutic potential of using leptin-based agents to treat AD. PMID:24298156

Alkyl-Capped Silicon Nanocrystals Lack Cytotoxicity and have Enhanced Intracellular Accumulation in Malignant Cells via Cholesterol-Dependent Endocytosis

PubMed Central

Alsharif, Naif H; Berger, Christine E M; Varanasi, Satya S; Chao, Yimin; Horrocks, Benjamin R; Datta, Harish K

2009-01-01

Nanocrystals of various inorganic materials are being considered for application in the life sciences as fluorescent labels and for such therapeutic applications as drug delivery or targeted cell destruction. The potential applications of the nanoparticles are critically compromised due to the well-documented toxicity and lack of understanding about the mechanisms involved in the intracellular internalization. Here intracellular internalization and toxicity of alkyl-capped silicon nanocrystals in human neoplastic and normal primary cells is reported. The capped nanocrystals lack cytotoxicity, and there is a marked difference in the rate and extent of intracellular accumulation of the nanoparticles between human cancerous and non-cancerous primary cells, the rate and extent being higher in the malignant cells compared to normal human primary cells. The exposure of the cells to the alkyl-capped nanocrystals demonstrates no evidence of in vitro cytotoxicity when assessed by cell morphology, apoptosis, and cell viability assays. The internalization of the nanocrystals by Hela and SW1353 cells is almost completely blocked by the pinocytosis inhibitors filipin, cytochalasin B, and actinomycin D. The internalization process is not associated with any surface change in the nanoparticles, as their luminescence spectrum is unaltered upon transport into the cytosol. The observed dramatic difference in the rate and extent of internalization of the nanocrystals between malignant and non-malignant cells therefore offers potential application in the management of human neoplastic conditions. PMID:19058285

Explosive sport training and torque kinetics in children.

PubMed

Dotan, Raffy; Mitchell, Cameron J; Cohen, Rotem; Gabriel, David; Klentrou, Panagiota; Falk, Bareket

2013-07-01

A high rate of force development (RFD) is often more important than maximal force in daily and sports activities. In children, resistance training has been shown to increase maximal force. It is unclear whether, or to what extent, can children improve RFD and force kinetics. For this study, we compared strength and force kinetics of boy gymnasts with those of untrained boys and untrained men. Eight boy gymnasts (age, 9.5 ± 1.2 y), 20 untrained boys (age, 10.1 ± 1.3 y), and 20 untrained men (age, 22.9 ± 4.4 y) performed maximal, explosive, isometric elbow flexions (EF) and knee flexions (KF). Peak torque (maximal voluntary contraction (MVC)), elapsed times to 10%-100% MVC, peak rate of torque development (RTDpk), and other kinetics parameters were determined. When gymnasts were compared with untrained boys, size-normalized EF MVC was 11%-20% higher, RTDpk was 32% higher, and times to 30% and 80% MVC were 16% and 55% shorter, respectively (p < 0.05). No corresponding differences were observed in KF. Furthermore, although the normalized EF MVC was 28% lower in gymnasts than in men (p < 0.001), their torque kinetics parameters were similar. These findings highlight the specificity of gymnastics training, which markedly elevated the torque kinetics of young, prepubertal boys to adult levels, but only moderately affected peak torque. It is suggested that neurologic adaptations, such as enhanced firing and activation rates or increased type II motor-unit recruitment, as well as changes in musculotendinous stiffness, could explain these findings.

Labisia pumila extract protects skin cells from photoaging caused by UVB irradiation.

PubMed

Choi, Hyun-kyung; Kim, Dong-hyun; Kim, Jin Wook; Ngadiran, Sulaiman; Sarmidi, Mohamad Roji; Park, Chang Seo

2010-03-01

Labisia pumila (Myrsinaceae), known as "Kacip Fatimah," has been used by many generations of Malay women to induce and facilitate child birth as well as a post partum medicine. However, its topical application on skin has not been reported yet. In this study, we have focused on the anti-photoaging effects of L. pumila. Extract of L. pumila was first analyzed for their antioxidant activities using DPPH (2,2-diphenyl-1-picrylhydrazyl) since UV irradiation is a primary cause of reactive oxygen species (ROS) generation in the skin. The 50% free radical scavenging activity (FSC(50)) of L. pumila extract was determined to be 0.006%, which was equal to that produced by 156 microM ascorbic acid. TNF-alpha and cyclooxygenase (COX-2) play a primary role in the inflammation process upon UV irradiation and are known to be stimulated by UVB. Treatment with L. pumila extract markedly inhibited the TNF-alpha production and the expression of COX-2. Decreased collagen synthesis of human fibroblasts by UVB was restored back to normal level after treatment with L. pumila extract. On the other hand, the enhanced MMP-1 expression upon UVB irradiation was down regulated by L. pumila extract in a dose-dependent manner. Furthermore, treatment of normal keratinocytes with L. pumila extract attenuated UVB-induced MMP-9 expression. These results collectively suggest L. pumila extract has tremendous potential as an anti-photoaging cosmetic ingredient. Copyright 2009. Published by Elsevier B.V.

Pharmacokinetic and Pharmacodynamic Interaction of Boswellic Acids and Andrographolide with Glyburide in Diabetic Rats: Including Its PK/PD Modeling.

PubMed

Samala, Sujatha; Veeresham, Ciddi

2016-03-01

The effect of boswellic acids (BA) and andrographolide (AD) on the pharmacokinetics and pharmacodynamics of glyburide in normal as well as in streptozotocin-induced diabetic rats was studied. In normal and diabetic rats, the combination of glyburide with BA or AD increased significantly (p < 0.01) all the pharmacokinetic parameters, such as Cmax, AUC0-n, AUCtotal, t1/2, and mean residence time, and decreased the clearance, Vd, markedly as compared with the control group. In rat liver, microsomes BA and AD have shown CYP3A4 inhibitory activity significantly (p < 0.01), compared with the vehicle group. The increase in hypoglycemic action by concomitant administration of glyburide with BA or AD was more in diabetic rats than when the drugs were used singly and with the control group, which suggests the enhancement of glucose reduction capacity of glyburide in diabetic rats along with BA or AD. In PK/PD modeling of BA and AD with glyburide, the predicted PK and PD parameters are in line with the observed PK and PD parameters. The results revealed that BA and AD led to the PK/PD changes because of glyburide-increased bioavailability and because of the inhibition of CYP3A4 enzyme. In conclusion, add-on preparations containing BA or AD may increase the bioavailability of glyburide, and hence the dose should be monitored. Copyright © 2016 John Wiley & Sons, Ltd.

Experimental application of thermosensitive paramagnetic liposomes for monitoring magnetic resonance imaging guided thermal ablation.

PubMed

Frich, Lars; Bjørnerud, Atle; Fossheim, Sigrid; Tillung, Terje; Gladhaug, Ivar

2004-12-01

The use of a liposomal paramagnetic agent with a T(1)-relaxivity that increases markedly at temperatures above the phase transition temperature (T(m)) of the liposomal membrane was evaluated during magnetic resonance imaging (MRI) guided hyperthermia ablation. A neodymium-yttrium aluminum garnet (Nd-YAG) laser unit and a radiofrequency ablation system were used for tissue ablation in eight rabbit livers in vivo. One ablation was made in each animal prior to administration of the liposomal agent. Liposomes with a T(m) of 57 degrees C containing gadodiamide (GdDTPA-BMA) were injected iv, and two additional ablations were performed. T(1)-weighted scans were performed in heated tissue, after tissue temperature had normalized, and 15-20 min after normalization of tissue temperature. Increase in signal intensity (DeltaSI) for ablations prior to injection of the agent was 13.0% (SD = 5.7) for the laser group and 9.1% (SD = 7.9) for the radiofrequency group. Signal intensity after administration of the agent unrelated to heating was not statistically significant (DeltaSI = 1.4%, P = 0.35). For ablations made after injection of the agent, a significant increase was found in the laser (DeltaSI = 34.5%, SD = 11.9) and radiofrequency group (DeltaSI = 21.6%, SD = 22.7). The persistent signal enhancement found in areas exposed to a temperature above the threshold temperature above T(m) allows thermal monitoring of MRI guided thermal ablation. (c) 2004 Wiley-Liss, Inc.

Lactobacillus casei HY7213 ameliorates cyclophosphamide-induced immunosuppression in mice by activating NK, cytotoxic T cells and macrophages.

PubMed

Jang, Se-Eun; Joh, Eun-Ha; Ahn, Young-Tae; Huh, Chul-Sung; Han, Myung Joo; Kim, Dong-Hyun

2013-06-01

Lactic acid bacteria (LAB) have recently attracted considerable attention as treatment options for immune diseases, the incidence of which has been increasing worldwide. The ability of tumor necrosis factor-α producing LAB isolated from cheese to inhibit NF-κB activation in lipopolysaccharide (LPS)-stimulated peritoneal macrophages was investigated. Among the tested LAB, Lactobacillus casei HY7213 inhibited NF-κB activation most potently. Therefore, we measured its immunopotentiating effect in cyclophosphamide (CP)-immunosuppressed mice. When HY7213 was orally administered for 5 or 15 d, it reversed the CP immunosuppressant effect by increasing body and spleen weights, blood red and white blood cells levels, and splenocyte and bone marrow cells counts. Treatment with CP in mice markedly reduced concanavalin A (ConA)-induced T cell proliferation to 54% compared to the normal group. Oral administration of HY7213 in CP-immunosuppressed mice reversed that value to 95% of the normal group on day 15. Furthermore, oral administration of HY7213 to CP-treated mice significantly enhanced the expression of IL-2 and IFN-γ in ConA-induced splenic cytotoxic T cells, restored the CP-impaired phagocytosis of macrophage, and increased the cytotoxicity of natural killer (NK) and cytotoxic T cells derived from spleen and bone marrow against YAC-1. Based on these findings, we suggest that HY7213 may promote the recovery of immunosuppression caused by chemotherapeutic agents, such as CP, by activating NK cells, cytotoxic T cells and macrophages.

Normal Faulting at the Western Margin of the Altiplano Plateau, Southern Peru

NASA Astrophysics Data System (ADS)

Schildgen, T. F.; Hodges, K. V.; Whipple, K. X.; Perignon, M.; Smith, T. M.

2004-12-01

Although the western margin of the Altiplano Plateau is commonly used to illustrate the marked differences in the evolution of a mountain range with strong latitudinal and longitudinal precipitation gradients, the nature of tectonism in this semi-arid region is poorly understood and much debated. The western margin of the Altiplano in southern Peru and northern Chile marks an abrupt transition from the forearc region of the Andes to the high topography of the Cordillera Occidental. This transition has been interpreted by most workers as a monocline, with modifications due to thrust faulting, normal faulting, and gravity slides. Based on recent fieldwork and satellite image analysis, we suggest that, at least in the semi-arid climate of southern Peru, this transition has been the locus of significant high-angle normal faulting related to the block uplift of the Cordillera Occidental. We have focused our initial work in the vicinity of 15\\deg S latitude, 71\\deg W longitude, where the range front crosses Colca Canyon, a major antecedent drainage northwest of Arequipa. In that area, Oligocene to Miocene sediments of the Moquegua Formation, which were eroded from uplifted terrain to the northeast, presently dip to the northeast at angles between 2 and 10º. Field observations of a normal fault contact between the Moquegua sedimentary rocks and Jurassic basement rocks, as well as 15-m resolution 3-D images generated from ASTER satellite imagery, show that the Moquegua units are down-dropped to the west across a steeply SW-dipping normal fault of regional significance. Morphology of the range front throughout southern Peru suggests that normal faulting along the range front has characterized the recent tectonic history of the region. We present geochronological data to constrain the timing of movement both directly from the fault zone as well as indirectly from canyon incision that likely responded to fault movement.

Normal Cognition and Behavior in a Smith-Lemli-Opitz Syndrome Patient Who Presented With Hirschsprung Disease

PubMed Central

Mueller, C.; Patel, S.; Irons, M.; Antshel, K.; Salen, G.; Tint, G.S.; Bay, C.

2005-01-01

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis. It is caused by mutations in the gene encoding the enzyme 7-dehydrocholesterol Δ7-reductase (DHCR7), which catalyzes the final step in cholesterol biosynthesis, usually resulting in cholesterol deficiency. We report a 3.5-year-old girl who has cognition in the low average range and normal behavior, but in whom molecular studies identified two missense mutations in DHCR7: V326L and F284L. She was born at term following an uncomplicated pregnancy and delivery, and presented at 12 days of age with poor feeding, abdominal distention, and jaundice. Colonic biopsy was consistent with Hirschsprung disease. On physical examination she had mild ptosis, a long philtrum, mild micrognathia, a short, upturned nose, and subtle 2,3 syndactyly. Her 7-dehydrocholesterol (7-DHC) level was markedly elevated at 8.7 mg/dl (normal 0.10 ± 0.05), and her cholesterol level was normal at 61 mg/dl (normal for newborn period 50–80 mg/dl). Karyotype analysis was normal, 46,XX. Breast milk feeding was initiated and continued for 18 months. Cholesterol supplementation was implemented at 100 mg/kg/day at 3 months, which resulted in increased cholesterol levels and reduced dehydrocholesterol levels. Neuropsychological testing has shown functioning in the low average range, between the 14th and 18th centiles when compared to peers. This is markedly higher than most children with SLOS. She has no behavioral problems. MRI and MRS testing of the brain revealed no structural abnormalities. This is in contrast to a recently reported case by Prasad et al. [2002: Am J Med Genet 108:64–68] with a mild phenotype, behavioral problems, and abnormal MRI, who is compound heterozygote for both a null and missense mutation. Our case suggests that patients with severe feeding disorders with or without Hirschprung disease and postnatal onset microcephaly may warrant screening for SLOS. PMID:14556255

Using new non-invasive quick method to detect Borrelia Burgdorferi (B.B.) infection from specific parts of the heart in "seemingly normal" ECGs, and from the ECGs of Atrial Fibrillation (AF), a majority of AF ECGs are found to have: 1) Significant B.B. infection, 2) Markedly increased ANP, 3) Increased Cardiac Troponin I & 4) Markedly reduced Taurine. These 4 factors were mainly localized at infected areas of the SA node area, R-&L-Atria & pulmonary veins at the L-atrium.

PubMed

Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

2015-01-01

Lyme disease is found in a majority of people we tested. Once Borrelia Burgdorferi (B.B.) spirochete enters human body, it not only causes pain by infecting joints, but it also often enters the brain and the heart. Infection of brain can be quickly detected from the pupil and infection of the heart by ECGs non-invasively. By evaluating recorded ECGs of atrial fibrillation (AF), using U.S. patented non-invasive highly sensitive electromagnetic field (EMF) resonance phenomenon between 2 identical molecules or between a molecule and its antibody, we examined 25 different AF patients' ECGs and found the majority of them suffer from various degrees of B.B. spirochete infection in SA node areas, also in the right & left atria, and pulmonary vein near and around its junction at left atrium & lesser degrees of infection at the AV node & His Bundle. When B.B. infection reaches over 224-600ng or higher at these areas, AF often appears in the majority of all AF analyzed. In order to develop AF, the 4 abnormal factors must be present simultaneously: 1) B.B. infection must be increased to 224-600ng or higher, 2) Atrial Natriuretic Peptide (ANP) must be markedly reduced from normal value of less than 4ng to over 100-400ng, 3) A significant increase of Cardiac Troponin I from normal value of less than 3ng to over 12ng and 4) Taurine must also be markedly reduced from normal value of 4-6ng to 0.25ng. These 4 changes were mainly found only at infected sites of the SA node area, both atria and between the end of the T wave & the beginning of the SA node area, which corresponds to U waves at recorded ECG. Origin of the U wave is mainly due to abnormal electrical potential of pulmonary vein at L-atrium. If all 4 factors do not occur at the infection site, no AF will develop. In seemingly normal ECGs, if using this method, one can detect invisible B.B. infection in early stages. Long before AF appears, AF can be prevented by improved treatment with Amoxicillin 500ng 3 times/day + Taurine 175mg x 3 times/day, with or without EPA 180 mg & DHA 120 mg, to avoid serious current limitations in the use of Doxycycline 100 mg 2 times/day, for 4 weeks.

Survival and endogenous colony formation in irradiated mice grafted with normal or infectious mononucleosis bone marrow

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

Louwagie, A. C.; Verwilghen, R. L.

1973-07-01

Mice were exposed to 850 or 975 rad of whole-body radiation; three hr later mice were given normal human bone marrow, infectious mononucleosis bone marrow, or cells from malignant blood diseases. The surviving mice were killed at day 9 and the spleen nodules were counted. Some mice were also given antihuman antilymphocytic serum (ALS). In mice exposed to 975 rad, the highest survival was observed in mice grafted with infectious mononucleosis bone marrow, while none of the animals grafted with cells from malignant blood diseases survived 9 days. In mice exposed to 850 rad, grafting of normal or infectious mononucleosismore » bone marrow markedly decreased the survival. Endogenous spleen colonies were induced in all animals grafted with normal or infectious mononucleosis bone marrow. (HLW)« less

Follow-up status of patients with angiographically normal coronary arteries and panic disorder

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

Beitman, B.D.; Kushner, M.G.; Basha, I.

1991-03-27

Cardiology patients with normal coronary angiography demonstrate continuing and substantial social, health, and work disability. The authors hypothesized that the diagnosis of panic disorder would mark those for whom continuing disability is most likely. They interviewed 72 such patients at the time of their normal angiogram, and then again an average of 38 months later. Those with panic disorder (n=36) demonstrated significantly more disability at follow-up than did the other study patients. They conclude that those patients with normal angiograms who have panic disorder are more disabled than those who do not have panic disorder. Panic disorder in psychiatric samplesmore » has been shown to be highly treatable. Therefore, early identification and treatment of panic disorder in this group is likely to minimize the suffering associated with this condition.« less

The potentiality of Trichoderma harzianum in alleviation the adverse effects of salinity in faba bean plants.

PubMed

Abd El-Baki, G K; Mostafa, Doaa

2014-12-01

The interaction between sodium chloride and Trichoderma harzianum (T24) on growth parameters, ion contents, MDA content, proline, soluble proteins as well as SDS page protein profile were studied in Vicia faba Giza 429. A sharp reduction was found in fresh and dry mass of shoots and roots with increasing salinity. Trichoderma treatments promoted the growth criteria as compared with corresponding salinized plants. The water content and leaf area exhibited a marked decrease with increasing salinity. Trichoderma treatments induced a progressive increase in both parameters. Both proline and MDA contents were increased progressively as the salinity rose in the soil. Trichoderma treatments considerably retarded the accumulation of both parameters in shoots and roots. Both Na+ and K+ concentration increased in both organs by enhancing salinity levels. The treatment with Trichoderma harzianum enhanced the accumulation of both ions. Exposure of plants to different concentrations of salinity, or others treated with Trichoderma harzianum produced marked changes in their protein pattern. Three types of alterations were observed: the synthesis of certain proteins declined significantly, specific synthesis of certain other proteins were markedly observed and synthesis of a set specific protein was induced de novo in plant treated with Trichoderma harzianum.

Glymphatic MRI in idiopathic normal pressure hydrocephalus

PubMed Central

Ringstad, Geir; Vatnehol, Svein Are Sirirud; Eide, Per Kristian

2017-01-01

Abstract The glymphatic system has in previous studies been shown as fundamental to clearance of waste metabolites from the brain interstitial space, and is proposed to be instrumental in normal ageing and brain pathology such as Alzheimer’s disease and brain trauma. Assessment of glymphatic function using magnetic resonance imaging with intrathecal contrast agent as a cerebrospinal fluid tracer has so far been limited to rodents. We aimed to image cerebrospinal fluid flow characteristics and glymphatic function in humans, and applied the methodology in a prospective study of 15 idiopathic normal pressure hydrocephalus patients (mean age 71.3 ± 8.1 years, three female and 12 male) and eight reference subjects (mean age 41.1 + 13.0 years, six female and two male) with suspected cerebrospinal fluid leakage (seven) and intracranial cyst (one). The imaging protocol included T1-weighted magnetic resonance imaging with equal sequence parameters before and at multiple time points through 24 h after intrathecal injection of the contrast agent gadobutrol at the lumbar level. All study subjects were kept in the supine position between examinations during the first day. Gadobutrol enhancement was measured at all imaging time points from regions of interest placed at predefined locations in brain parenchyma, the subarachnoid and intraventricular space, and inside the sagittal sinus. Parameters demonstrating gadobutrol enhancement and clearance in different locations were compared between idiopathic normal pressure hydrocephalus and reference subjects. A characteristic flow pattern in idiopathic normal hydrocephalus was ventricular reflux of gadobutrol from the subarachnoid space followed by transependymal gadobutrol migration. At the brain surfaces, gadobutrol propagated antegradely along large leptomeningeal arteries in all study subjects, and preceded glymphatic enhancement in adjacent brain tissue, indicating a pivotal role of intracranial pulsations for glymphatic function. In idiopathic normal pressure hydrocephalus, we found delayed enhancement (P < 0.05) and decreased clearance of gadobutrol (P < 0.05) at the Sylvian fissure. Parenchymal (glymphatic) enhancement peaked overnight in both study groups, possibly indicating a crucial role of sleep, and was larger in normal pressure hydrocephalus patients (P < 0.05 at inferior frontal gyrus). We interpret decreased gadobutrol clearance from the subarachnoid space, along with persisting enhancement in brain parenchyma, as signs of reduced glymphatic clearance in idiopathic normal hydrocephalus, and hypothesize that reduced glymphatic function is instrumental for dementia in this disease. The study shows promise for glymphatic magnetic resonance imaging as a method to assess human brain metabolic function and renders a potential for contrast enhanced brain extravascular space imaging. PMID:28969373

Glymphatic MRI in idiopathic normal pressure hydrocephalus.

PubMed

Ringstad, Geir; Vatnehol, Svein Are Sirirud; Eide, Per Kristian

2017-10-01

The glymphatic system has in previous studies been shown as fundamental to clearance of waste metabolites from the brain interstitial space, and is proposed to be instrumental in normal ageing and brain pathology such as Alzheimer's disease and brain trauma. Assessment of glymphatic function using magnetic resonance imaging with intrathecal contrast agent as a cerebrospinal fluid tracer has so far been limited to rodents. We aimed to image cerebrospinal fluid flow characteristics and glymphatic function in humans, and applied the methodology in a prospective study of 15 idiopathic normal pressure hydrocephalus patients (mean age 71.3 ± 8.1 years, three female and 12 male) and eight reference subjects (mean age 41.1 + 13.0 years, six female and two male) with suspected cerebrospinal fluid leakage (seven) and intracranial cyst (one). The imaging protocol included T1-weighted magnetic resonance imaging with equal sequence parameters before and at multiple time points through 24 h after intrathecal injection of the contrast agent gadobutrol at the lumbar level. All study subjects were kept in the supine position between examinations during the first day. Gadobutrol enhancement was measured at all imaging time points from regions of interest placed at predefined locations in brain parenchyma, the subarachnoid and intraventricular space, and inside the sagittal sinus. Parameters demonstrating gadobutrol enhancement and clearance in different locations were compared between idiopathic normal pressure hydrocephalus and reference subjects. A characteristic flow pattern in idiopathic normal hydrocephalus was ventricular reflux of gadobutrol from the subarachnoid space followed by transependymal gadobutrol migration. At the brain surfaces, gadobutrol propagated antegradely along large leptomeningeal arteries in all study subjects, and preceded glymphatic enhancement in adjacent brain tissue, indicating a pivotal role of intracranial pulsations for glymphatic function. In idiopathic normal pressure hydrocephalus, we found delayed enhancement (P < 0.05) and decreased clearance of gadobutrol (P < 0.05) at the Sylvian fissure. Parenchymal (glymphatic) enhancement peaked overnight in both study groups, possibly indicating a crucial role of sleep, and was larger in normal pressure hydrocephalus patients (P < 0.05 at inferior frontal gyrus). We interpret decreased gadobutrol clearance from the subarachnoid space, along with persisting enhancement in brain parenchyma, as signs of reduced glymphatic clearance in idiopathic normal hydrocephalus, and hypothesize that reduced glymphatic function is instrumental for dementia in this disease. The study shows promise for glymphatic magnetic resonance imaging as a method to assess human brain metabolic function and renders a potential for contrast enhanced brain extravascular space imaging. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Active thermography and post-processing image enhancement for recovering of abraded and paint-covered alphanumeric identification marks

NASA Astrophysics Data System (ADS)

Montanini, R.; Quattrocchi, A.; Piccolo, S. A.

2016-09-01

Alphanumeric marking is a common technique employed in industrial applications for identification of products. However, the realised mark can undergo deterioration, either by extensive use or voluntary deletion (e.g. removal of identification numbers of weapons or vehicles). For recovery of the lost data many destructive or non-destructive techniques have been endeavoured so far, which however present several restrictions. In this paper, active infrared thermography has been exploited for the first time in order to assess its effectiveness in restoring paint covered and abraded labels made by means of different manufacturing processes (laser, dot peen, impact, cold press and scribe). Optical excitation of the target surface has been achieved using pulse (PT), lock-in (LT) and step heating (SHT) thermography. Raw infrared images were analysed with a dedicated image processing software originally developed in Matlab™, exploiting several methods, which include thermographic signal reconstruction (TSR), guided filtering (GF), block guided filtering (BGF) and logarithmic transformation (LN). Proper image processing of the raw infrared images resulted in superior contrast and enhanced readability. In particular, for deeply abraded marks, good outcomes have been obtained by application of logarithmic transformation to raw PT images and block guided filtering to raw phase LT images. With PT and LT it was relatively easy to recover labels covered by paint, with the latter one providing better thermal contrast for all the examined targets. Step heating thermography never led to adequate label identification instead.

Hypogammaglobulinemia associated with accelerated catabolism of IgG secondary to its interaction with an IgG-reactive monoclonal IgM

PubMed Central

Waldmann, Thomas A.; Johnson, John S.; Talal, Norman

1971-01-01

Hypogammaglobulinemia due to a new pathophysiological mechanism was studied in a patient with Sjögren's syndrome, a monoclonal IgM and a mixed (IgM-IgG) cryoglobulinemia. The IgM (IgMdk) component of the cryogel possessed light chains of λ-type with highly restricted electrophoretic mobility analagous to those of a Waldenström's macroglobulin. IgMdk reacted specifically with native IgG, with IgG subclasses 1, 2, and 4, and with the Fc piece of IgG to form a cryogel. Serum concentrations of IgG 1, 2, and 4 were 10% of normal, whereas the IgG3 level was slightly increased and the IgM level was markedly increased. Viscosity and analytical ultracentrifugation studies with the purified mixed cryogel (IgM-LgG) indicated soluble complex formation over a temperature range (36-38°C) attainable in vivo. Immunoglobulin turnover studies revealed a markedly elevated rate of IgM synthesis with a normal survival of IgM, IgA, and IgE. IgG3, which failed to form complexes with IgMdk at body temperature, had a normal synthetic rate and survival. In contrast, the other IgG subclasses showed reduced synthesis and shortened survival. These studies are the first indicating a short survival of some IgG subclasses with a normal survival of another. The hypogammaglobulinemia appears to be due in part to a new mechanism of accelerated protein catabolism: The rapid elimination of IgG due to its interaction with an IgG-reactive monoclonal IgM. PMID:4993860

[A case of chronic multifocal myositis].

PubMed

Maruyama, T; Kondo, K; Tabata, K; Yanagisawa, N

1992-11-01

A 61-year-old civil engineer began to have slowly progressive muscle atrophy in the right shoulder and the left arm at 56 years of age. Muscle wasting became manifest in the left thigh at 59 years and in the right thigh at 60 years. He had mild difficulty in climbing and descending stairs. On examination, although he had notable muscle atrophy in the right trapezius and proximal muscles in the upper and lower extremities, his muscle strength was relatively well preserved. The muscle atrophy was asymmetrical; the right periscapular region and the left upper and lower extremities were more markedly atrophic. In addition, multiple foci of the striking muscle atrophy were noted in the upper trunk and the proximal limb muscles. Fasciculation was not present. Deep tendon reflexes were normal with no pathologic reflexes. Except for a moderately elevated serum creatine kinase level of 709 Ul/l (normal 40-170) and mildly elevated serum myoglobin level of 100 ng/ml (normal < 60), no laboratory tests showed abnormal values suggesting an inflammatory process. Motor and sensory nerve conduction velocities were within normal limits. Electromyography disclosed myopathic and neuropathic changes. Computed tomography (CT) of skeletal muscles showed asymmetrical muscle atrophy and patchy low-density foci. In biopsied left quadriceps and right gastrocnemius muscles which showed partially low density on CT, there was marked variation in muscle fiber size, with necrotic and regenerating fibers, an increased number of centrally placed nuclei, and interstitial fibrosis. There were numerous foci of mononuclear inflammatory cellular infiltration, especially around the blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Computation of distribution of minimum resolution for log-normal distribution of chromatographic peak heights.

PubMed

Davis, Joe M

2011-10-28

General equations are derived for the distribution of minimum resolution between two chromatographic peaks, when peak heights in a multi-component chromatogram follow a continuous statistical distribution. The derivation draws on published theory by relating the area under the distribution of minimum resolution to the area under the distribution of the ratio of peak heights, which in turn is derived from the peak-height distribution. Two procedures are proposed for the equations' numerical solution. The procedures are applied to the log-normal distribution, which recently was reported to describe the distribution of component concentrations in three complex natural mixtures. For published statistical parameters of these mixtures, the distribution of minimum resolution is similar to that for the commonly assumed exponential distribution of peak heights used in statistical-overlap theory. However, these two distributions of minimum resolution can differ markedly, depending on the scale parameter of the log-normal distribution. Theory for the computation of the distribution of minimum resolution is extended to other cases of interest. With the log-normal distribution of peak heights as an example, the distribution of minimum resolution is computed when small peaks are lost due to noise or detection limits, and when the height of at least one peak is less than an upper limit. The distribution of minimum resolution shifts slightly to lower resolution values in the first case and to markedly larger resolution values in the second one. The theory and numerical procedure are confirmed by Monte Carlo simulation. Copyright © 2011 Elsevier B.V. All rights reserved.

Modulation of cytotoxic T lymphocyte, natural killer cell, antibody-dependent cellular cytotoxicity, and antibody-dependent complement-mediated cytotoxicity by Vernonia cinerea L. and vernolide-A in BALB/c mice via enhanced production of cytokines IL-2 and IFN-γ.

PubMed

Pratheeshkumar, Poyil; Kuttan, Girija

2012-02-01

Effect of Vernonia cinerea L. and vernolide-A on cell-mediated immune (CMI) response was studied in normal as well as tumor-bearing BALB/c mice. Administration of V. cinerea and vernolide-A significantly enhanced natural killer (NK) cell activity in both normal as well as tumor-bearing animals, and the activity was observed earlier than in tumor-bearing control animals. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement-mediated cytotoxicity (ACC) were also enhanced significantly in both normal as well as tumor-bearing animals after V. cinerea and vernolide-A administration compared with untreated control tumor-bearing animals. Extract and vernolide-A showed a significant increase in cytotoxic T lymphocyte (CTL) production in both the in vivo and in vitro models. The level of cytokines such as interleukin (IL)-2 and interferon (IFN)-γ were also enhanced by the treatment of V. cinerea and vernolide-A in both normal as well as tumor-bearing animals. This study demonstrated that V. cinerea extract and vernolide-A stimulate the CTL, NK cell, ADCC, and ADCC through enhanced secretion of IL-2 and IFN-γ.

Strongly Modulated Friction of a Film-Terminated Ridge-Channel Structure.

PubMed

He, Zhenping; Hui, Chung-Yuen; Levrard, Benjamin; Bai, Ying; Jagota, Anand

2016-05-26

Natural contacting surfaces have remarkable surface mechanical properties, which has led to the development of bioinspired surface structures using rubbery materials with strongly enhanced adhesion and static friction. However, sliding friction of structured rubbery surfaces is almost always significantly lower than that of a flat control, often due to significant loss of contact. Here we show that a film-terminated ridge-channel structure can strongly enhance sliding friction. We show that with properly chosen materials and geometrical parameters the near surface structure undergoes mechanical instabilities along with complex folding and sliding of internal interfaces, which is responsible for the enhancement of sliding friction. Because this structure shows no enhancement of adhesion under normal indentation by a sphere, it breaks the connection between energy loss during normal and shear loading. This makes it potentially interesting in many applications, for instance in tires, where one wishes to minimize rolling resistance (normal loading) while maximizing sliding friction (shear loading).

Enhanced contractility of the rat stomach during suppression of angiotensin converting enzyme by captopril in vitro.

PubMed Central

Rani, R.; Rao, K. S.

1991-01-01

1. Intragastric pressure (IGP) was used as an index, of the effect of serosal application of captopril (SQ 14,225; D-3-mercapto-2-methylpropanoyl-L-proline) on the contractility of rat stomach in vitro. 2. Captopril, at concentrations greater than 0.3 microM, enhanced the spontaneous gastric motility (GM) in a concentration-dependent manner whereas concentrations less than 0.3 microM selectively potentiated 4 nM bradykinin (BK)-evoked gastric contractions without significantly affecting the spontaneous GM. 3. The kallikrein inhibitor, aprotinin (100 u ml-1), markedly antagonized the enhanced GM to 1.4 microM captopril and BK (4 nM)-evoked contractions, without affecting the contractions evoked by angiotensin 1 (10 nM) and acetylcholine (0.4 microM). The angiotensin II antagonist, saralasin (50 microM) failed to mimic aprotinin. 4. The enhanced GM to captopril was markedly inhibited by tetrodotoxin (1 microM), and partially inhibited by atropine (1 microM). 5. These results indicate that in vitro, captopril (greater than 0.3 microM) enhances gastric contractility through kininase/ACE inhibitory action, presumably by increasing the concentration of undegraded tissue kinins and substance P. This motor response seems to be predominantly due to activation of the cholinergic neurones but non-cholinergic excitatory neurones are also involved. PMID:1713107

An intracellular matrix metalloproteinase-2 isoform induces tubular regulated necrosis: implications for acute kidney injury.

PubMed

Ceron, Carla S; Baligand, Celine; Joshi, Sunil; Wanga, Shaynah; Cowley, Patrick M; Walker, Joy P; Song, Sang Heon; Mahimkar, Rajeev; Baker, Anthony J; Raffai, Robert L; Wang, Zhen J; Lovett, David H

2017-06-01

Acute kidney injury (AKI) causes severe morbidity, mortality, and chronic kidney disease (CKD). Mortality is particularly marked in the elderly and with preexisting CKD. Oxidative stress is a common theme in models of AKI induced by ischemia-reperfusion (I-R) injury. We recently characterized an intracellular isoform of matrix metalloproteinase-2 (MMP-2) induced by oxidative stress-mediated activation of an alternate promoter in the first intron of the MMP-2 gene. This generates an NH 2 -terminal truncated MMP-2 (NTT-MMP-2) isoform that is intracellular and associated with mitochondria. The NTT-MMP-2 isoform is expressed in kidneys of 14-mo-old mice and in a mouse model of coronary atherosclerosis and heart failure with CKD. We recently determined that NTT-MMP-2 is induced in human renal transplants with delayed graft function and correlated with tubular cell necrosis. To determine mechanism(s) of action, we generated proximal tubule cell-specific NTT-MMP-2 transgenic mice. Although morphologically normal at the light microscopic level at 4 mo, ultrastructural studies revealed foci of tubular epithelial cell necrosis, the mitochondrial permeability transition, and mitophagy. To determine whether NTT-MMP-2 expression enhances sensitivity to I-R injury, we performed unilateral I-R to induce mild tubular injury in wild-type mice. In contrast, expression of the NTT-MMP-2 isoform resulted in a dramatic increase in tubular cell necrosis, inflammation, and fibrosis. NTT-MMP-2 mice had enhanced expression of innate immunity genes and release of danger-associated molecular pattern molecules. We conclude that NTT-MMP-2 "primes" the kidney to enhanced susceptibility to I-R injury via induction of mitochondrial dysfunction. NTT-MMP-2 may be a novel AKI treatment target.

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica

PubMed Central

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 (DaCBF4), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4-overexpressing transgenic rice plant (Ubi:DaCBF4) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice. PMID:29774046

Enhanced midbrain response at 6-month follow-up in cocaine addiction, association with reduced drug-related choice: Midbrain in drug choice

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

Moeller, Scott J.; Tomasi, Dardo; Woicik, Patricia A.

Drug addiction is characterized by dysregulated dopamine neurotransmission. Although dopamine functioning appears to partially recover with abstinence, the specific regions that recover and potential impact on drug seeking remain to be determined. Here we used functional magnetic resonance imaging (fMRI) to study an ecologically valid sample of 15 treatment-seeking cocaine addicted individuals at baseline and 6-month follow-up. At both study sessions, we collected fMRI scans during performance of a drug Stroop task, clinical self-report measures of addiction severity and behavioral measures of cocaine seeking (simulated cocaine choice); actual drug use in between the two study sessions was also monitored. Atmore » 6-month follow-up (compared with baseline), we predicted functional enhancement of dopaminergically innervated brain regions, relevant to the behavioral responsiveness toward salient stimuli. Consistent with predictions, whole-brain analyses revealed responses in the midbrain (encompassing the ventral tegmental area/substantia nigra complex) and thalamus (encompassing the mediodorsal nucleus) that were higher (and more positively correlated) at follow-up than baseline. Increased midbrain activity from baseline to follow-up correlated with reduced simulated cocaine choice, indicating that heightened midbrain activations in this context may be marking lower approach motivation for cocaine. Normalization of midbrain function at follow-up was also suggested by exploratory comparisons with active cocaine users and healthy controls (who were assessed only at baseline). Enhanced self-control at follow-up was suggested by a trend for the commonly hypoactive dorsal anterior cingulate cortex to increase response during a drug-related context. Together, these results suggest that fMRI could be useful in sensitively tracking follow-up outcomes in drug addiction.« less

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica.

PubMed

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 ( DaCBF4 ), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4 -overexpressing transgenic rice plant ( Ubi:DaCBF4 ) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice.

High targeted migration of human mesenchymal stem cells grown in hypoxia is associated with enhanced activation of RhoA

PubMed Central

2013-01-01

Introduction A feature which makes stem cells promising candidates for cell therapy is their ability to migrate effectively into damaged or diseased tissues. Recent reports demonstrated the increased motility of human mesenchymal stem cells (hMSC) grown under hypoxic conditions compared to normoxic cells. However, the directional migration of hMSC cultured in hypoxia has not been investigated. In this study we examined the in vitro transmembrane migration of hMSC permanently cultured in hypoxia in response to various cytokines. We also studied the involvement of RhoA, a molecule believed to play an essential role in the migration of MSC via reorganization of the cytoskeleton. Methods We compared the directional migration of human hMSCs grown permanently under normal (21%, normoxic) and low O2 (5%, hypoxic) conditions until passage 4 using an in vitro transmembrane migration assay. A series of 17 cytokines was used to induce chemotaxis. We also compared the level of GTP-bound RhoA in the cell extracts of calpeptin-activated hypoxic and normoxic hMSC. Results We found that hMSC cultured in hypoxia demonstrate markedly higher targeted migration activity compared to normoxic cells, particularly towards wound healing cytokines, including those found in ischemic and myocardial infarction. We also demonstrated for the first time that hMSC are dramatically more sensitive to activation of RhoA. Conclusions The results of this study indicate that high directional migration of hMSCs permanently grown in hypoxia is associated with the enhanced activation of RhoA. The enhanced migratory capacity of hypoxic hMSC would further suggest their potential advantages for clinical applications. PMID:23295150

Milrinone enhances relaxation to prostacyclin and iloprost in pulmonary arteries isolated from lambs with persistent pulmonary hypertension of the newborn

PubMed Central

Lakshminrusimha, Satyan; Porta, Nicolas F. M.; Farrow, Kathryn N.; Chen, Bernadette; Gugino, Sylvia F.; Kumar, Vasanth H.; Russell, James A.; Steinhorn, Robin H.

2009-01-01

Prostacyclin is a pulmonary vasodilator and is produced by prostacyclin synthase and stimulates adenylate cyclase (AC) via the prostacyclin receptor (IP) to produce cAMP. Forskolin is a direct stimulant of AC. Phosphodiesterase 3 hydrolyzes cAMP and is inhibited by milrinone. Objective To characterize the prostacyclin-AC-cAMP pathway in the ovine ductal ligation model of persistent pulmonary hypertension of the newborn (PPHN). Setting University-based laboratory animal facility. Subjects Lambs delivered to time-dated pregnant ewes. Interventions Fifth generation pulmonary arteries (PA) and lung parenchyma were isolated from control fetal lambs (n = 8) and fetal lambs with PPHN induced by antenatal ductal ligation (n = 9). We studied relaxation responses to various agonists (milrinone, forskolin, prostacyclin, and iloprost, a prostacyclin analog) that increase cAMP in PA after half-maximal constriction with norepinephrine and pretreatment with propranolol ± indo-methacin. Lung protein levels of prostacyclin synthase, IP, AC2, and phosphodiesterase 3A were analyzed by Western blot and cAMP by enzyme-linked immunoassay. Main Results Milrinone relaxed control and PPHN PA and pretreatment with indomethacin significantly impaired this response. Relaxation to milrinone, prostacyclin, and iloprost were significantly impaired in PA from PPHN lambs. Pretreatment with milrinone markedly enhanced relaxation to prostacyclin and iloprost in PPHN PA, similar to relaxation in control PA. Relaxation to forskolin was similar in control and PPHN PAs indicating normal AC activity. Protein levels of prostacyclin synthase and IP were decreased in PPHN lungs compared with control, but AC2, cAMP, and phosphodiesterase 3A remained unchanged. Conclusions Prostacyclin and iloprost are dilators of PAs from PPHN lambs and their effect is enhanced by milrinone. This combination therapy may be an effective strategy in the management of patients with PPHN. PMID:19057444

Analysis of expression of FLI1 and MMP1 in American cutaneous leishmaniasis caused by Leishmania braziliensis infection.

PubMed

Almeida, Lucas; Silva, Juliana A; Andrade, Viviane M; Machado, Paulo; Jamieson, Sarra E; Carvalho, Edgar M; Blackwell, Jenefer M; Castellucci, Léa C

2017-04-01

FLI1 (Friend leukemia virus integration 1) and IL6 (interleukin 6; IL-6) are associated with Leishmania braziliensis susceptibility. Cutaneous lesions show exaggerated matrix metalloproteinase 1 (MMP1). In other skin diseases, FLI1 promoter methylation reduces FLI1 expression, and low FLI1 down-regulates MMP1. IL-6 increases FLI1 expression. We hypothesized that epigenetic regulation of FLI1 in cutaneous leishmaniasis, together with IL-6, might determine MMP1 expression. While generally low (<10%), percent FLI1 promoter methylation was lower (P=0.001) in lesion biopsies than normal skin. Contrary to expectation, a strong positive correlation occurred between FLI1 methylation and gene expression in lesions (r=0.98, P=0.0005) and in IL-6-treated L. braziliensis-infected macrophages (r=0.99, P=0.0004). In silico analysis of the FLI1 promoter revealed co-occurring active H3K27ac and repressive DNA methylation marks to enhance gene expression. FLI1 expression was enhanced between 3 and 24hour post infection in untreated (P=0.0002) and IL-6-treated (P=0.028) macrophages. MMP1 was enhanced in lesion biopsies (P=0.0002), induced (P=0.007) in infected macrophages, but strongly inhibited by IL-6. No correlations occurred between FLI1 and MMP1 expression in lesions or infected macrophages (with/without IL-6). We conclude that MMP1 is regulated by factors other than FLI1, and that the influence of IL-6 on MMP1 was independent of its effect on FLI1. Copyright © 2017 Elsevier B.V. All rights reserved.

Determinants of the Thrombogenic Potential of Multiwalled Carbon Nanotubes

PubMed Central

Burke, Andrew; Singh, Ravi; Carroll, David L.; Owen, John; Kock, Nancy D.; D’Agostino, Ralph; Torti, Frank M.; Torti, Suzy V.

2011-01-01

Multiwalled carbon nanotubes (MWCNTs) are cylindrical tubes of graphitic carbon with unique physical and electrical properties. MWCNTs are being explored for a variety of diagnostic and therapeutic applications. Successful biomedical application of MWCNTs will require compatibility with normal circulatory components, including constituents of the hemostatic cascades. In this manuscript, we compare the thrombotic activity of MWCNTs in vitro and in vivo. We also assess the influence of functionalization of MWCNTs on thrombotic activity. In vitro, MWCNT activate the intrinsic pathway of coagulation as measured by activated partial thromboplastin time (aPTT) assays. Functionalization by amidation or carboxylation enhances this procoagulant activity. Mechanistic studies demonstrate that MWCNTs enhance propagation of the intrinsic pathway via a non-classical mechanism strongly dependent on factor IX. MWCNTs preferentially associate with factor IXa and may provide a platform for its activation. In addition to their effects on the coagulation cascade, MWCNTs activate platelets in vitro, with amidated MWCNTs exhibiting greater platelet activation than carboxylated or pristine MWCNTs. However, contrasting trends are obtained in vivo, where functionalization tends to diminish rather than enhance pro-coagulant activity. Thus, following systemic injection of MWCNTs in mice, pristine MWCNTs decreased platelet counts, increased vWF, and increased D-dimers. In contrast, carboxylated MWCNTS exhibited little procoagulant tendency in vivo, eliciting only a mild and transient decrease in platelets. Amidated MWCNTs elicited no statistically significant change in platelet count. Further, neither carboxylated nor amidated MWCNTs increased vWF or D-dimers in mouse plasma. We conclude that the pro-coagulant tendencies of MWCNTs observed in vitro are not necessarily recapitulated in vivo. Further, functionalization can markedly attenuate the procoagulant activity of MWCNTs in vivo. This work will inform the rational development of biocompatible MWCNTs for systemic delivery. PMID:21663954

Acotiamide hydrochloride (Z-338) enhances gastric motility and emptying by inhibiting acetylcholinesterase activity in rats.

PubMed

Kawachi, Masanao; Matsunaga, Yugo; Tanaka, Takao; Hori, Yuko; Ito, Katsunori; Nagahama, Kenji; Ozaki, Tomoko; Inoue, Naonori; Toda, Ryoko; Yoshii, Kazuyoshi; Hirayama, Masamichi; Kawabata, Yoshihiro; Takei, Mineo

2011-09-01

In clinical trials, acotiamide hydrochloride (acotiamide: Z-338) has been reported to be useful in the treatment of functional dyspepsia. Here, we investigated the effects of acotiamide on gastric contraction and emptying activities in rats in comparison with itopride hydrochloride (itopride) and mosapride citrate (mosapride). We also examined in vitro the compound's inhibitory effect on acetylcholinesterase (AChE) activity derived from rat stomach. In in vivo studies, acotiamide (30 and 100mg/kg s.c.) and itopride (100mg/kg s.c.) markedly enhanced normal gastric antral motility in rats. In gastric motility dysfunction models, acotiamide (100mg/kg s.c.) and itopride (100mg/kg s.c.) improved both gastric antral hypomotility and the delayed gastric emptying induced by clonidine, an α(2)-adrenoceptor agonist. In contrast, mosapride (10mg/kg s.c.) had no effect on these models. Like the AChE inhibitors itopride (30 mg/kg s.c.) and neostigmine (10 μg/kg s.c.), acotiamide (10mg/kg s.c.) also clearly enhanced gastric body contractions induced by electrical stimulation of the vagus, which were abolished by atropine and hexamethonium, whereas mosapride (3 and 10mg/kg s.c.) did not. In in vitro studies, acotiamide concentration-dependently inhibited rat stomach-derived AChE activity (IC(50)=2.3 μmol/l). In addition, stomach tissue concentrations of acotiamide after administration at 10mg/kg s.c. were sufficient to produce inhibition of AChE activity in rat stomach. These results suggest that acotiamide stimulates gastric motility and improves gastric motility dysfunction in rats by inhibiting AChE activity, and may suggest a role for acotiamide in improving gastric motility dysfunction in patients with functional dyspepsia. Copyright © 2011 Elsevier B.V. All rights reserved.

Immune stimulation by a CpG-containing oligodeoxynucleotide is enhanced when encapsulated and delivered in lipid particles.

PubMed

Mui, B; Raney, S G; Semple, S C; Hope, M J

2001-09-01

The therapeutic benefit from phosphorothioate oligodeoxynucleotides (PS ODN) containing immune stimulatory sequences (ISS) has been demonstrated in animal models of cancer and infection. In particular, when CpG-containing PS ODN are administered to mice, activation of macrophages and dendritic, NK, T, and B cells occurs, resulting in the release of an array of cytokines, including interleukin-12 (IL-12), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). We have previously described stabilized antisense-lipid particles (SALP) for the i.v. administration of antisense ODN [Biochim Biophys Acta (2001) 1510:152--166]. Given the propensity for SALP to target macrophages in vivo it was of interest to determine whether they could enhance the potency of CpG ODN to induce an immune response. In this report we show that when CpG-containing SALP are administered intravenously to ICR mice the plasma concentrations of IL-12, IFN-gamma, IL-6, monocyte chemoattractant protein-1, and TNF-alpha are greatly increased compared with the same dose of free ODN. The pattern of cytokine induction indicates that the immune response is T helper cell type 1-biased, similar to that observed for PS CpG ODN ISS in general. Furthermore, when phosphodiester (PO) ODN is substituted for PS ODN in the SALP formulation cytokine induction is even greater at the early time points, in marked contrast to free PO ODN, which is inactive. These results demonstrate that the immunogenicity of ISS is not only enhanced by encapsulation in lipid particles, which more closely mimic the way ISS DNA would normally be presented to antigen presenting cells by pathogens in vivo, but also SALP enable unmodified PO CpG ODN to be used as immune stimulants.

Senescent fibroblasts enhance early skin carcinogenic events via a paracrine MMP-PAR-1 axis.

PubMed

Malaquin, Nicolas; Vercamer, Chantal; Bouali, Fatima; Martien, Sébastien; Deruy, Emeric; Wernert, Nicolas; Chwastyniak, Maggy; Pinet, Florence; Abbadie, Corinne; Pourtier, Albin

2013-01-01

The incidence of carcinoma increases greatly with aging, but the cellular and molecular mechanisms underlying this correlation are only partly known. It is established that senescent fibroblasts promote the malignant progression of already-transformed cells through secretion of inflammatory mediators. We investigated here whether the senescent fibroblast secretome might have an impact on the very first stages of carcinogenesis. We chose the cultured normal primary human epidermal keratinocyte model, because after these cells reach the senescence plateau, cells with transformed and tumorigenic properties systematically and spontaneously emerge from the plateau. In the presence of medium conditioned by autologous senescent dermal fibroblasts, a higher frequency of post-senescence emergence was observed and the post-senescence emergent cells showed enhanced migratory properties and a more marked epithelial-mesenchymal transition. Using pharmacological inhibitors, siRNAs, and blocking antibodies, we demonstrated that the MMP-1 and MMP-2 matrix metalloproteinases, known to participate in late stages of cancer invasion and metastasis, are responsible for this enhancement of early migratory capacity. We present evidence that MMPs act by activating the protease-activated receptor 1 (PAR-1), whose expression is specifically increased in post-senescence emergent keratinocytes. The physiopathological relevance of these results was tested by analyzing MMP activity and PAR-1 expression in skin sections. Both were higher in skin sections from aged subjects than in ones from young subjects. Altogether, our results suggest that during aging, the dermal and epidermal skin compartments might be activated coordinately for initiation of skin carcinoma, via a paracrine axis in which MMPs secreted by senescent fibroblasts promote very early epithelial-mesenchymal transition of keratinocytes undergoing transformation and oversynthesizing the MMP-activatable receptor PAR-1.

Expression and function of the atypical cadherin FAT1 in chronic liver disease.

PubMed

Valletta, Daniela; Czech, Barbara; Thasler, Wolfgang E; Müller, Martina; Bosserhoff, Anja-Katrin; Hellerbrand, Claus

2012-09-28

Hepatic fibrosis can be considered as wound healing process in response to hepatocellular injury. Activation of hepatic stellate cells (HSCs) is a key event of hepatic fibrosis since activated HSCs are the cellular source of enhanced extracellular matrix deposition, and reversion of liver fibrosis is accompanied by clearance of activated HSCs by apoptosis. The atypical cadherin FAT1 has been shown to regulate diverse biological functions as cell proliferation and planar cell polarity, and also to affect wound healing. Here, we found increased FAT1 expression in different murine models of chronic liver injury and in cirrhotic livers of patients with different liver disease. Also in hepatic tissue of patients with non-alcoholic steatohepatitis FAT1 expression was significantly enhanced and correlated with collagen alpha I(1) expression. Immunohistochemistry revealed no significant differences in staining intensity between hepatocytes in normal and cirrhotic liver tissue but myofibroblast like cells in fibrotic septa of cirrhotic livers showed a prominent immunosignal. Furthermore, FAT1 mRNA and protein expression markedly increased during in vitro activation of primary human and murine HSCs. Together, these data indicated activated HSCs as cellular source of enhanced FAT1 expression in diseased livers. To gain insight into the functional role of FAT1 in activated HSCs we suppressed FAT1 in these cells by siRNA. We newly found that FAT1 suppression in activated HSCs caused a downregulation of NFκB activity. This transcription factor is critical for apoptosis resistance of HSCs, and consequently, we detected a higher apoptosis rate in FAT1 suppressed HSCs compared to control cells. Our findings suggest FAT1 as new therapeutic target for the prevention and treatment of hepatic fibrosis in chronic liver disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Delineating the Construct Network of the Personnel Reaction Blank: Associations with Externalizing Tendencies and Normal Personality

ERIC Educational Resources Information Center

Blonigen, Daniel M.; Patrick, Christopher J.; Gasperi, Marianna; Steffen, Benjamin; Ones, Deniz S.; Arvey, Richard D.; de Oliveira Baumgartl, Viviane; do Nascimento, Elizabeth

2011-01-01

Integrity testing has long been utilized in personnel selection to screen for tendencies toward counterproductive workplace behaviors. The construct of externalizing from the psychopathology literature represents a coherent spectrum marked by disinhibitory traits and behaviors. The present study drew on a sample of male and female undergraduates…

Human prolactin - 24-hour pattern with increased release during sleep.

NASA Technical Reports Server (NTRS)

Sassin, J. F.; Weitzman, E. D.; Kapen, S.; Frantz, A. G.

1972-01-01

Human prolactin was measured in plasma by radioimmunoassay at 20-minute intervals for a 24-hour period in each of six normal adults, whose sleep-wake cycles were monitored polygraphically. A marked diurnal variation in plasma concentrations was demonstrated, with highest values during sleep. Periods of episodic release occurred throughout the 24 hours.

Localization in Multiple Source Environments: Localizing the Missing Source

DTIC Science & Technology

2007-02-01

volunteer listeners (3 males and 3 females, 19-24 years of age ), participated in the experiment. All had normal hearing (au- diometric thresholds < 15...were routed from a control computer to a Mark of the Unicorn digital-to-analog con- verter (MOTU 24 I/O), then through a bank of amplifiers (Crown Model

Realization of Complex Onsets by Pediatric Users of Cochlear Implants

ERIC Educational Resources Information Center

Chin, Steven B.

2006-01-01

This study examined variations in English complex onset realizations by children who use cochlear implants. Data consisted of 227 productions of two-segment onset clusters from 12 children. In general, onset cluster realizations of children with cochlear implants did not differ markedly from those reported for children with normal hearing: null…

Stress-induced ascorbic acid depletion and cortisol production in two salmonid fishes

USGS Publications Warehouse

Wedemeyer, Gary

1969-01-01

Interrenal ascorbic acid and serum cortisol were measured in non-specificity stressed yearling coho salmon and rainbow trout.Interrenal ascorbate was markedly decreased during stress but increased to normal if adaptation occurred.Serum cortisol was elevated by non-specific stress and remained high after interrenal ascorbate had returned to initial levels.

Discordant hepatic uptake between Tc-99m sulfur colloid and Tc-99m DISIDA in hypervitaminosis A

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

Vincent, L.M.; McCartney, W.H.; Mauro, M.A.

1984-02-01

Scintigraphic findings in a patient with biopsy-proven hypervitaminosis A included markedly impaired hepatic uptake of Tc-99m sulfur colloid but essentially normal uptake of Tc-99m DISIDA. This case presents a potential cause for image discordance with these two agents.

Nonlinear dynamics in ecosystem response to climatic change: case studies and policy implications.

Treesearch

Virginia R. Burkett; Douglas A. Wilcox; Robert Stottlemeyer; Wylie Barrow; Dan Fagre; Jill Baron; Jeff Price; Jennifer L. Nielsen; Craig D. Allen; David L. Peterson; Greg Ruggerone; Thomas Doyle

2005-01-01

Many biological, hydrological, and geological processes are interactively linked in ecosystems. These ecological phenomena normally vary within bounded ranges, but rapid, nonlinear changes to markedly different conditions can be triggered by even small differences if threshold values are exceeded. Intrinsic and extrinsic ecological thresholds can lead to effects that...

Galantamine Facilitates Acquisition of Hippocampus-Dependent Trace Eyeblink Conditioning in Aged Rabbits

ERIC Educational Resources Information Center

Weible, Aldis P.; Oh, M. Matthew; Lee, Grace; Disterhoft, John F.

2004-01-01

Cholinergic systems are critical to the neural mechanisms mediating learning. Reduced nicotinic cholinergic receptor (nAChR) binding is a hallmark of normal aging. These reductions are markedly more severe in some dementias, such as Alzheimer's disease. Pharmacological central nervous system therapies are a means to ameliorate the cognitive…

How to Distinguish Normal from Disordered Children with Poor Language or Motor Skills

ERIC Educational Resources Information Center

Dyck, Murray; Piek, Jan

2010-01-01

Background & Aims: We tested the Diagnostic and Statistical Manual of Mental Disorders (DSM) hypothesis that so-called specific developmental disorders are marked by a pattern of specific discrepant achievement, and an alternative hypothesis that children with these disorders show a pattern of relatively pervasive low achievement. Methods…

78 FR 42809 - Self-Regulatory Organizations; Fixed Income Clearing Corporation; Order Approving Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-17

... remain subject to all of the GSD's normal risk management procedures, which include marking member portfolios to the market on an intraday basis and charging variation margins accordingly.\\19\\ These risk management procedures should help ensure the safety of the securities and funds handled by the GSD in...

Changing the Perspective on Early Development of Rett Syndrome

ERIC Educational Resources Information Center

Marschik, Peter B.; Kaufmann, Walter E.; Sigafoos, Jeff; Wolin, Thomas; Zhang, Dajie; Bartl-Pokorny, Katrin D.; Pini, Giorgio; Zappella, Michele; Tager-Flusberg, Helen; Einspieler, Christa; Johnston, Michael V.

2013-01-01

We delineated the achievement of early speech-language milestones in 15 young children with Rett syndrome ("MECP2" positive) in the first two years of life using retrospective video analysis. By contrast to the commonly accepted concept that these children are normal in the pre-regression period, we found markedly atypical development of…

Some Growth Aspects of Seymeria cassioicies

Treesearch

Charles M. Stangle; Lytton J. Musselman

1981-01-01

The root parasite, Seymeria cassioides, will not initiate height growth without attachment to a host root when grown under normal fertility conditions, although the seedling may remain alive for 40 days or more without a host. During this time the roots elongate markedly. Fresh pine root segments do not influence the direction of root growth. Although S....

Intermittent maple syrup urine disease: two case reports.

PubMed

Axler, Olof; Holmquist, Peter

2014-02-01

The presenting symptoms and clinical course of 2 cases of intermittent maple syrup urine disease (MSUD) are described. Intermittent MSUD is a potentially life-threatening metabolic disorder caused by a deficiency of branched-chain α-keto acid dehydrogenase, the enzyme complex that decarboxylates the 3 branched-chain amino acids. In contrast to classic MSUD, children with the intermittent form show normal development with normal intelligence and, when asymptomatic, normal levels of branched-chain amino acids. Symptoms usually appear between 5 months and 2 years of age, when a trivial infection such as otitis media or viral gastroenteritis triggers catabolism of muscle protein. Intermittent MSUD should be suspected in cases of common infections with a clinically atypical course, especially in children displaying ataxia or marked drowsiness.

Groups at potentially high risk from chlorine dioxide treated water.

PubMed

Moore, G S; Calabrese, E J; Ho, S C

1980-09-01

Chlorite, a by-product of chlorine dioxide disinfection of water, is a strong oxidant compound that produces markedly exaggerated effects in vitro on red cells of G6PD deficient humans when compared to normal human cells. Levels of methemoglobin are significantly greater and GSH levels significantly lower in the G6PD deficient cells than in normal cells after chlorite exposure. Persons with G6PD deficiency may be 3 to 4 times more likely to develop hemolytic anemia from chlorite exposure as persons with normal activity levels when GSH levels are used as a measure of susceptibility. The proposed use of chlorine dioxide as an alternate disinfectant for drinking water supplies should consider this potential high risk group.

Deformations and Structural Evolution of Mesozoic Complexes in Western Chukotka

NASA Astrophysics Data System (ADS)

Golionko, B. G.; Vatrushkina, E. V.; Verzhbitskii, V. E.; Sokolov, S. D.; Tuchkova, M. I.

2018-01-01

Detailed structural investigations have been carried out in the Pevek district to specify tectonic evolution of the Chukotka mesozoids. The earliest south-verging folds F1 formed in Triassic rocks at the first deformation stage DI. These structures are overlapped by the northern-verging folds F2 and overthrusts pertain to the second deformation stage DII. Folding structures F1 and F2 were deformed by shear folds F3, completing stage DII. The DI and DII structures are complicated by roughly NS-trending normal faults marking deformation stage DIII. It has been established that DI is related to the onset of opening of the Amerasian Basin in the Early Jurassic, or, alternatively, to the later accretion of the Kulpolnei ensimatic arc toward the Chukotka microcontinent. DII marks the collision of Siberia and the Chukotka microcontinent in the Late Neocomian. Normal faulting under the roughly E-W-trending extension during DIII is likely related to rift opening of the Podvodnikov and Makarov-Toll basins in the deep Amerasian Basin. Formation of the Okhotsk-Chukotka volcanoplutonic belt completed the structural evolution of the studied region.

Pathologic childhood aerophagia: a recognizable clinical entity.

PubMed

Gauderer, M W; Halpin, T C; Izant, R J

1981-06-01

Pathologic childhood aerophagia is a rarely recognized, often poorly treated entity that has remained almost undescribed in either the surgical or pediatric literature. In only 1 of 9 children the condition was recognized at presentation. The initial diagnosis of the others was Hirschsprung's disease (2), malabsorption syndrome (3), gastric outlet syndrome (1), constipation (1), and esophagitis (1). Five were hospitalized and two underwent surgical procedures. History disclosed a remarkably constant triad: previous normal stooling pattern, visible and often audible air swallowing and excessive flatus. Physical examination often demonstrated a markedly or intermittently distended and tympanitic abdomen. Abdominal musculature was thinned in children with chronic aerophagia. Roentgenographic evaluation showed massively distended loops of intestine throughout without associated air-fluid levels. There was marked compression of the diaphragm with limited excursion in some. Laboratory and malabsorption testing was normal. Treatment is limited to recognition of the problem, nasogastric decompression in severe cases and psychologic counseling when symptoms persist in the older child. The recognition of this condition may lead to a better understanding of its pathophysiology and will reduce the number of unnecessary admissions or surgical procedures.

Shunting normal-pressure hydrocephalus: do the benefits outweigh the risks? A multicenter study and literature review.

PubMed

Vanneste, J; Augustijn, P; Dirven, C; Tan, W F; Goedhart, Z D

1992-01-01

We performed a multicenter retrospective study in 166 consecutive patients shunted for presumed normal-pressure hydrocephalus (NPH) in the four neurosurgical departments of Amsterdam. Overall improvement occurred in 36%, substantial improvement in 21%. In the subgroup of idiopathic NPH (N = 127), marked improvement was only 15%. The incidence of shunt-responsive NPH in our area was 2.2/million/year. The rate of severe and moderate shunt-related complications was 28%, leading to death or severe residual morbidity in 7%. The substantial benefit/serious harm ration in the whole group was only three (21%/7%), decreasing to 1.7 in idiopathic NPH. By excluding patients at high surgical risk, this ratio might have risen to 10 in the whole group and to six in idiopathic NPH. Our experience is much less favorable than that encountered in the literature, reporting overall improvement in 74% and marked improvement in 55% of the shunted patients. We conclude that NPH is probably a very rare and still overdiagnosed syndrome and that the overall morbidity rate for each patient demonstrating meaningful improvement is high.

Enhanced facial texture illumination normalization for face recognition.

PubMed

Luo, Yong; Guan, Ye-Peng

2015-08-01

An uncontrolled lighting condition is one of the most critical challenges for practical face recognition applications. An enhanced facial texture illumination normalization method is put forward to resolve this challenge. An adaptive relighting algorithm is developed to improve the brightness uniformity of face images. Facial texture is extracted by using an illumination estimation difference algorithm. An anisotropic histogram-stretching algorithm is proposed to minimize the intraclass distance of facial skin and maximize the dynamic range of facial texture distribution. Compared with the existing methods, the proposed method can more effectively eliminate the redundant information of facial skin and illumination. Extensive experiments show that the proposed method has superior performance in normalizing illumination variation and enhancing facial texture features for illumination-insensitive face recognition.

Ultrafast Bilateral DCE-MRI of the Breast with Conventional Fourier Sampling: Preliminary Evaluation of Semi-quantitative Analysis.

PubMed

Pineda, Federico D; Medved, Milica; Wang, Shiyang; Fan, Xiaobing; Schacht, David V; Sennett, Charlene; Oto, Aytekin; Newstead, Gillian M; Abe, Hiroyuki; Karczmar, Gregory S

2016-09-01

The study aimed to evaluate the feasibility and advantages of a combined high temporal and high spatial resolution protocol for dynamic contrast-enhanced magnetic resonance imaging of the breast. Twenty-three patients with enhancing lesions were imaged at 3T. The acquisition protocol consisted of a series of bilateral, fat-suppressed "ultrafast" acquisitions, with 6.9- to 9.9-second temporal resolution for the first minute following contrast injection, followed by four high spatial resolution acquisitions with 60- to 79.5-second temporal resolution. All images were acquired with standard uniform Fourier sampling. A filtering method was developed to reduce noise and detect significant enhancement in the high temporal resolution images. Time of arrival (TOA) was defined as the time at which each voxel first satisfied all the filter conditions, relative to the time of initial arterial enhancement. Ultrafast images improved visualization of the vasculature feeding and draining lesions. A small percentage of the entire field of view (<6%) enhanced significantly in the 30 seconds following contrast injection. Lesion conspicuity was highest in early ultrafast images, especially in cases with marked parenchymal enhancement. Although the sample size was relatively small, the average TOA for malignant lesions was significantly shorter than the TOA for benign lesions. Significant differences were also measured in other parameters descriptive of early contrast media uptake kinetics (P < 0.05). Ultrafast imaging in the first minute of dynamic contrast-enhanced magnetic resonance imaging of the breast has the potential to add valuable information on early contrast dynamics. Ultrafast imaging could allow radiologists to confidently identify lesions in the presence of marked background parenchymal enhancement. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Expression of beta-dystroglycan is reduced or absent in many human carcinomas.

PubMed

Cross, S S; Lippitt, J; Mitchell, A; Hollingsbury, F; Balasubramanian, S P; Reed, M W R; Eaton, C; Catto, J W; Hamdy, F; Winder, S J

2008-11-01

Dystroglycan is an important structural and signalling protein that is expressed in most human cells. alpha-Dystroglycan has been investigated and found to be reduced in human cancers, but there is only one published study on the expression of beta-dystroglycan in human cancer and that was only on small numbers of breast and prostatic cancers. The aim was to conduct a comprehensive immunohistochemical survey of the expression of beta-dystroglycan in normal human tissues and common cancers. Triplicate tissue microarrays of 681 samples of normal human tissues and common cancers were stained using an antibody directed against the cytoplasmic component of beta-dystroglycan. beta-Dystroglycan was strongly expressed at the intercellular junctions and basement membranes of all normal human epithelia. Expression of beta-dystroglycan was absent or markedly reduced in 100% of oesophageal adenocarcinomas, 97% of colonic cancers, 100% of transitional cell carcinomas of the urothelium and 94% of breast cancers. In the breast cancers, the only tumours that showed any retention of beta-dystroglycan expression were small low-grade oestrogen receptor-positive tumours. The only cancers that showed retention of beta-dystroglycan expression were cutaneous basal cell carcinomas. There is loss or marked reduction of beta-dystroglycan expression (by immunohistochemistry) in the vast majority of human cancers surveyed. Since beta-dystroglycan is postulated to have a tumour suppressor effect, this loss may have important functional significance.

Effects of 60-Hz electric fields on serotonin metabolism in the rat pineal gland

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

Anderson, L.E.; Hilton, D.I.; Phillips, R.D.

Serotonin and two of its metabolites, melatonin and 5-methoxytryptophol, exhibit circadian rhythmicity in the pineal gland. We recently reported a marked reduction in the normal night-time increase in melatonin concentration in the pineal glands of rats exposed to 60-Hz electric fields. Concomitant with the apparent abolition of melatonin rhythmicity, serotonin-N-acetyl transferase (SNAT) activity was suppressed. We have now conducted studies to determine if abolition of the rhythm in melatonin production in electric-field-exposed rats arises solely from interference in SNAT activity, or if the availability of pineal serotonin is a factor that is affected by exposure. Pineal serotonin concentrations were comparedmore » in rats that were either exposed or sham exposed to 65 kV/m for 30 days. Sham-exposed animals exhibited normal diurnal rhythmicity for pineal concentrations of both melatonin and serotonin; melatonin levels increased markedly during the dark phase with a concurrent decrease in serotonin levels. In the exposed animals, however, normal serotonin rhythmicity was abolished; serotonin levels in these animals did not increase during the light period. The conclusion that electric field exposure results in a biochemical alteration in SNAT enzyme activity can be inferred from the loss of both serotonin and melatonin rhythmicity, as well as by direct measurement of SNAT activity itself. 35 references, 3 figures, 1 table.« less

Hypoglycemia, hepatic dysfunction, muscle weakness, cardiomyopathy, free carnitine deficiency and long-chain acylcarnitine excess responsive to medium chain triglyceride diet.

PubMed

Glasgow, A M; Engel, A G; Bier, D M; Perry, L W; Dickie, M; Todaro, J; Brown, B I; Utter, M F

1983-05-01

Fraternal twins who had fasting hypoglycemia, hypoketonemia, muscle weakness, and hepatic dysfunction are reported. The hepatic dysfunction occurred only during periods of caloric deprivation. The surviving patient developed a cardiomyopathy. In this sibling, muscle weakness and cardiomyopathy were markedly improved by a diet high in medium chain triglycerides. There was a marked deficiency of muscle total carnitine and a mild deficiency of hepatic total carnitine. Unlike patients with systemic carnitine deficiency, serum and muscle long-chain acylcarnitine were elevated and renal reabsorption of carnitine was normal. It was postulated that the defect in long-chain fatty acid oxidation in this disorder is caused by an abnormality in the mitochondrial acylcarnitine transport. Detailed studies of the cause of the hypoglycemia revealed that insulin, growth hormone, cortisol, and glucagon secretion were appropriate and that it is unlikely that there was a major deficiency of a glycolytic or gluconeogenic enzyme. Glucose production and alanine conversion to glucose were in the low normal range when compared to normal children in the postabsorptive state. The hypoglycemia in our patients was probably due to a modest increase in glucose consumption, secondary to the decreased oxidation of fatty acids and ketones, alternate fuels which spare glucose utilization, plus a modest decrease in hepatic glucose production secondary to decreased available hepatic energy substrates.

TU-CD-BRA-11: Application of Bone Suppression Technique to Inspiratory/expiratory Chest Radiography

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

Tanaka, R; Sanada, S; Sakuta, K

Purpose: The bone suppression technique based on advanced image processing can suppress the conspicuity of bones on chest radiographs, creating soft tissue images normally obtained by the dual-energy subtraction technique. This study was performed to investigate the usefulness of bone suppression technique in quantitative analysis of pulmonary function in inspiratory/expiratory chest radiography. Methods: Commercial bone suppression image processing software (ClearRead; Riverain Technologies) was applied to paired inspiratory/expiratory chest radiographs of 107 patients (normal, 33; abnormal, 74) to create corresponding bone suppression images. The abnormal subjects had been diagnosed with pulmonary diseases, such as pneumothorax, pneumonia, emphysema, asthma, and lung cancer.more » After recognition of the lung area, the vectors of respiratory displacement were measured in all local lung areas using a cross-correlation technique. The measured displacement in each area was visualized as displacement color maps. The distribution pattern of respiratory displacement was assessed by comparison with the findings of lung scintigraphy. Results: Respiratory displacement of pulmonary markings (soft tissues) was able to be quantified separately from the rib movements on bone suppression images. The resulting displacement map showed a left-right symmetric distribution increasing from the lung apex to the bottom region of the lung in many cases. However, patients with ventilatory impairments showed a nonuniform distribution caused by decreased displacement of pulmonary markings, which were confirmed to correspond to area with ventilatory impairments found on the lung scintigrams. Conclusion: The bone suppression technique was useful for quantitative analysis of respiratory displacement of pulmonary markings without any interruption of the rib shadows. Abnormal areas could be detected as decreased displacement of pulmonary markings. Inspiratory/expiratory chest radiography combined with the bone suppression technique has potential for predicting local lung function on the basis of dynamic analysis of pulmonary markings. This work was partially supported by Nakatani Foundation, Grant-in-aid for Scientific Research (C) of Ministry of Education, Culture, Sports, Science and Technology, JAPAN (Grant number : 24601007), and Nakatani Foundation, Mitsubishi Foundation, and the he Mitani Foundation for Research and Development. Yasushi Kishitani is a staff of TOYO corporation.« less

[Value of non-invasive models of liver fibrosis in judgment of treatment timing in chronic hepatitis B patients with ALT < 2×upper limit of normal].

PubMed

Zhou, Q Q; Hu, Y B; Zhou, K; Zhang, W W; Li, M H; Dong, P; Di, J G; Hong, L; Du, Q W; Xie, Y; Sun, Q F

2016-09-20

Objective: To investigate the value of non-invasive liver fibrosis models, FIB-4, S index, aspartate aminotransferase to platelet ratio index(APRI), globulin-platelet(GP)model, aspartate aminotransferase/platelet/gamma-glutamyl transpeptidase/alpha-fetoprotein(APGA), and platelet/age/phosphatase/alpha-fetoprotein/aspartate aminotransferase(PAPAS), in the diagnosis of marked liver fibrosis in chronic hepatitis B(CHB)patients with ALT < 2×upper limit of normal(ULN), as well as treatment timing for this population. Methods: A total of 389 CHB patients with ALT < 2×ULN who were admitted to Beijing Ditan Hospital and whose treatment timing was difficult to judge were enrolled. Transdermal liver biopsy was performed to obtain pathological results, and routine serological tests were performed, including routine blood test, serum biochemical parameters, hepatitis B virus(HBV)markers, and HBV DNA. According to liver pathology, the patients were divided into non-marked liver fibrosis group(S < 2)with 324 patients and marked liver fibrosis group(S≥2)with 65 patients. The non-invasive models for predicting liver fibrosis was established with reference to original articles. SPSS 19.0 software was used for statistical analysis, and the receiver operating characteristic(ROC)curve was used to compare the value of different non-invasive models in predicting marked liver fibrosis in this population. Results: All the non-invasive models had a certain diagnostic value for liver fibrosis degree in these patients, and the areas under the ROC curve for APRI, FIB-4, APGA, S index, PAPAS, and GP model were 0.718, 0.691, 0.758, 0.729, 0.673, and 0.691, respectively. APGA had the largest area under the ROC curve(0.758, 95% CI 0.673-0.844), and gamma-glutamyl transpeptidase was significantly positively correlated with liver fibrosis degree. Conclusion: The non-invasive models of liver fibrosis can identify marked liver fibrosis in CHB patients with ALT < 2×ULN in whom it is difficult to judge treatment timing and help to determine treatment timing for them. APGA model has the highest value and can reduce the need for liver biopsy to the certain degree.

MRI of normal and abnormal duodenum using Half-Fourier Single-Shot RARE and gadolinium-enhanced spoiled gradient echo sequences.

PubMed

Marcos, H B; Semelka, R C; Noone, T C; Woosley, J T; Lee, J K

1999-07-01

The objective of this research was two-fold: First, to describe the normal and abnormal MR appearances of the duodenum using combined Half-Fourier Acquisition Single Shot RARE (HASTE) and gadolinium-enhanced standard and fat suppressed spoiled gradient echo (SGE) sequences. The second objective was to assess the ability of these combined sequences to detect and characterize duodenal diseases. MR examinations were performed on fifty consecutive patients with no clinical history of duodenal diseases, who were 1) imaged with HASTE and gadolinium-enhanced standard and fat suppressed SGE sequences and 2) referred to MR examination for reasons other than duodenal diseases, and were reviewed retrospectively to determine the normal MR appearances of the duodenum. A second population of patients with abnormal duodenum who were imaged with the same MR sequences were included in the second part of this study. This population was composed of 20 consecutive patients with subsequently proven duodenal abnormalities, including: malrotation (2), diverticula (4), intussusception (1), sprue (1), polyps (2), neurofibroma (1), lymphoma (1), Zollinger Ellison syndrome (1), metastatic disease (1), Crohn's disease (1), and wall thickening and duodenitis (5). Normal measurements of the duodenum are described. Abnormalities of wall thickness and duodenal masses required combined HASTE and gadolinium-enhanced SGE images to evaluate well. Abnormalities of the bowel lumen (e.g., diverticula and intussusception), and developmental variants (e.g., malrotation), were sufficiently visualized on HASTE images alone. Bowel inflammation was best shown on gadolinium-enhanced fat suppressed SGE images. HASTE and gadolinium-enhanced fat suppressed SGE sequences are complementary techniques for the demonstration of normal and abnormal duodenum. The combined use of both sequences allows evaluation of different aspects of bowel diseases; abnormalities of position, lumen, and contents are well shown on HASTE, while inflammation is best shown on gadolinium enhanced fat suppressed SGE, and wall thickening and masses are best evaluated with the combined use of both techniques.

Lethal short-limbed chondrodysplasia in early infancy.

PubMed

Yang, S S; Heidelberger, K P; Brough, A J; Corbett, D P; Bernstein, J

1976-01-01

Nineteen cases of chondrodysplastic short-limbed dwarfism in early infancy were studied in the context of current clinical classification based on established radiographic criteria. The histopathologic findings were sufficiently distinctive in most categories to provide additional diagnostic criteria and to contribute to the understanding and delineation of these disorders. 1. Homozygous achondroplasia is distinguished by markedly disturbed endochondral ossification that differs from the pattern seen in typical heterozygous achondroplasia. The physeal chondrocytes contain abundant granules of glycogen. 2. Achondrogenesis, the severest form of chondrodysplasia, exists in 2 types, in which the histopathologic findings appear to be distinctive and diagnostic. Type 1 is characterized by severe disturbance in endochondral ossification. The zone of resting cartilage contains relatively normal matrix, and the chondrocytes contain intracytoplasmic inclusions. The cartilaginous matrix in type 2 is markedly deficient, and the chondrocytes have a large, primitive, mesenchymatous appearance. 3. Thanatophoric dwarfism is associated with disorganized endochondral ossification similar to that in homozygous achondroplasia, but there is no accumulation of glycogen within chondrocytes. Type 2 thanatophoric dwarfism is differentiated from classical type 1 by the presence of cloverleaf skull and histologically by many bone-lined, penetrating vascular canals in the physis and by hyperactive osteoblasts and osteoclasts in the metaphysis. 4. Asphyxiating thoracic dysplasia of Jeune is differentiated histologically into 2 types. Type 1 is characterized by patchy distribution of endochondral ossification in the physis, irregular physeal-metaphyseal junction and large islands of poorly mineralized cartilage in the metaphysis. Type 2 is characterized by uniform distribution of endochondral ossification that is disorganized and is accompanied by advancing cartilage forming latticelike meshwork in the metaphysis. 5. Chondroectodermal dysplasia, which is radiographically similar to asphyxiating thoracic dysplasia, is marked by the presence of large islands of poorly mineralized cartilage in the spongiosa of vertebral bodies. Disorganized endochondral ossification is, however, uniformly distributed, and there is no latticelike advancing cartilage in the metaphysis. 6. Chondrodysplasia punctata is characterized by myxoid and cystic degeneration of physeal and epiphyseal cartilage with focal calcification. Type 2 (Conradi-Hünermann) has a nearly normal pattern of endochondral ossification, even though there may be severe disturbance and retardation of the process. The columnization of physeal chondrocytes is normal. Type 1 (rhizomelic) differs by having markedly retarded and disorganized endochondral ossification. 7...

Thrombopoietin: biology and clinical potentials.

PubMed

Miyazaki, H; Kato, T

1999-12-01

Thrombopoietin (TPO) is the principal physiologic regulator of platelet production. In vitro, TPO induces the growth of colony-forming units-megakaryocyte (CFU-MK) and the generation of mature polyploid megakaryocytes, which subsequently form extended cytoplasmic processes, termed proplatelets. On more differentiated CFU-MK, but not on megakaryocytes, TPO is critical for enhancing proplatelet formation. TPO has multilineage effects in hematopoiesis, not only stimulating megakaryocytopoiesis but also acting in synergy with other cytokines to enhance proliferation and survival of committed erythroid progenitors and primitive hematopoietic stem cells. Surface c-MPL, the receptor for TPO, defines a phenotype of hematopoietic stem cells with long-term repopulating ability. Treatment with various cytokine combinations, including TPO, results in an extensive ex vivo expansion of hematopoietic stem cells and blood cell precursors. In normal animals, pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) or glycosylated TPO increases the number of bone marrow megakaryocytes and their progenitors and greatly enhance the production of morphologically and functionally normal platelets. In contrast, they have only minimal effects on peripheral white blood cell and red blood cell counts. PEG-rHuMGDF used alone markedly expands circulating levels of multiple types of hematopoietic progenitors, and its effect is enhanced in combination with granulocyte colony-stimulating factor (G-CSF). Although PEG-rHuMGDF augments platelet aggregation induced by agonists in vitro, it has no influence in an animal model of thrombus formation. PEG-rHuMGDF or glycosylated TPO has a profound effect in a variety of animal models of thrombocytopenia, including myelosuppressive therapy. PEG-rHuMGDF treatment accelerates multilineage hematopoietic recovery, effectively improving thrombocytopenia, and, in most models, neutropenia and anemia. The concurrent administration of PEG-rHuMGDF and G-CSF does not interfere with the in vivo activity of cytokines but rather has synergistic effects. To further accelerate hematopoietic recovery, PEG-rHuMGDF administration should start at the earliest time following myelosuppressive treatment; this time sensitivity may result from the presence of a greater number of residual hematopoietic progenitors in the bone marrow soon after treatment. Moreover, if a relatively large dose of PEG-rHuMGDF is administered, a single intravenous injection is fully effective in improving impaired hematopoiesis. This effectiveness appears to be related to the persistence of PEG-rHuMGDF in the circulation. The safety and efficacy of two forms of the recombinant hormone, PEG-rHuMDGF and glycosylated human full-length TPO produced in mammalian cells, are currently under clinical investigation.

SOME EVIDENCE OF PSYCHIC BLINDNESS IN MONKEYS WITH FOCAL-HEAD IRRADIATION OF THE TEMPORAL LOBES

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

McDowell, A.A.; Brown, W.L.

1963-12-01

This study was conducted to compare the effects of various extra-cage social stimuli on the free-cage behavior of normal monkeys and of monkeys with previous focal-head irradiation. Four control and four focal-head irradiated monkeys with nearly identical training histories were used, the latter being the survivors of a focal-head irradiation study conducted 41/2 yr earlier. They had received 3000 r x radiation to an area of the head containing the inferior parietal lobule and posterior aspect of the temporal lobe, and repeated 30 days later Each group was systematically observed under each of four socialstimulus conditions with the order ofmore » condition presentation counterbalanced within each group over a 4-day period. The four social-stimulus conditions included: absence of social stimulus, an adult male monkey, an adult female monkey at menses, and an adult female monkey at estimated time of ovulation. The socialstimulus conditions showed no effect on the nondirected activities of the normal monkeys, but produced a marked decrease in the nondirected activities of the focal-head irradiated monkeys, with the least number of such activities being manifest in the presence of the adult female monkey at ovulation. Under conditions of social stimulation the normal monkeys showed a marked decrease in total directed activities of the non-social-stimulus condition, while the focal-head irradiated monkeys showed a marked increase, the effect in each instance being greatest in the presence of the female at ovulation. The directed activities, toward the cage as an object, of the controls decreasrd and those of the experimental subjects increased. The controls were more than twice as responsive to the female at estimated time of ovulation as to the other two social stimuli, while the experimental monkeys were equally responsive to each of the three social stimuli. The data suggest the presence of psychic blindness in the monkeys previously exposed to focal-head irradiation of the temporal lobes. (BBB)« less

Histone H3K9 Trimethylase Eggless Controls Germline Stem Cell Maintenance and Differentiation

PubMed Central

Zhou, Jian; McDowell, William; Park, Jungeun; Haug, Jeff; Staehling, Karen; Tang, Hong; Xie, Ting

2011-01-01

Epigenetic regulation plays critical roles in the regulation of cell proliferation, fate determination, and survival. It has been shown to control self-renewal and lineage differentiation of embryonic stem cells. However, epigenetic regulation of adult stem cell function remains poorly defined. Drosophila ovarian germline stem cells (GSCs) are a productive adult stem cell system for revealing regulatory mechanisms controlling self-renewal and differentiation. In this study, we show that Eggless (Egg), a H3K9 methyltransferase in Drosophila, is required in GSCs for controlling self-renewal and in escort cells for regulating germ cell differentiation. egg mutant ovaries primarily exhibit germ cell differentiation defects in young females and gradually lose GSCs with time, indicating that Egg regulates both germ cell maintenance and differentiation. Marked mutant egg GSCs lack expression of trimethylated H3K9 (H3k9me3) and are rapidly lost from the niche, but their mutant progeny can still differentiate into 16-cell cysts, indicating that Egg is required intrinsically to control GSC self-renewal but not differentiation. Interestingly, BMP-mediated transcriptional repression of differentiation factor bam in marked egg mutant GSCs remains normal, indicating that Egg is dispensable for BMP signaling in GSCs. Normally, Bam and Bgcn interact with each other to promote GSC differentiation. Interestingly, marked double mutant egg bgcn GSCs are still lost, but their progeny are able to differentiate into 16-cell cysts though bgcn mutant GSCs normally do not differentiate, indicating that Egg intrinsically controls GSC self-renewal through repressing a Bam/Bgcn-independent pathway. Surprisingly, RNAi-mediated egg knockdown in escort cells leads to their gradual loss and a germ cell differentiation defect. The germ cell differentiation defect is at least in part attributed to an increase in BMP signaling in the germ cell differentiation niche. Therefore, this study has revealed the essential roles of histone H3K9 trimethylation in controlling stem cell maintenance and differentiation through distinct mechanisms. PMID:22216012

Enhancing nitrite inhibition of Clostridium botulinum with isoascorbate in perishable canned cured meat.

PubMed Central

Tompkin, R B; Christiansen, L N; Shaparis, A B

1978-01-01

Addition of sodium isoascorbate to the formulation for perishable canned comminuted cured meat markedly enhanced the efficacy of nitrite against Clostridium botulinum. This effect was reproducible through a series of three tests. In one test it was found that the initial addition of 50 microgram of sodium nitrite per g plus isoascorbate was as effective as 156 microgram of sodium nitrite per g alone. PMID:341810

Biomedical enhancements as justice.

PubMed

Nam, Jeesoo

2015-02-01

Biomedical enhancements, the applications of medical technology to make better those who are neither ill nor deficient, have made great strides in the past few decades. Using Amartya Sen's capability approach as my framework, I argue in this article that far from being simply permissible, we have a prima facie moral obligation to use these new developments for the end goal of promoting social justice. In terms of both range and magnitude, the use of biomedical enhancements will mark a radical advance in how we compensate the most disadvantaged members of society. © 2013 John Wiley & Sons Ltd.

Enhancement of oxidative vaporization of chromium (III) oxide and chromium by oxygen atoms

NASA Technical Reports Server (NTRS)

Fryburg, G. C.; Kohl, F. J.; Stearns, C. A.

1974-01-01

Rates of oxidative vaporization of Cr2O3 were found to be markedly enhanced in the presence of O atoms. Investigations were conducted over the temperature range 470 to 1520 K. For Cr2O3 the enhancement was about 10 to the 9th power at 820 K in oxygen containing 2.5 percent atoms. Rapid oxidative vaporization of bare chromium was observed below 1070 K, the rate being about one-half that of Cr2O3. Results are interpreted in terms of thermochemical analysis.

Neural Methods for Imagery, GMTI, and Information Fusion

DTIC Science & Technology

2006-03-15

Dynamic Range Contrast Enhanced Length & Power Normalized JV\\ 0.7 11 2500. No0 00 0.6 :a -30 - i 0.5 1 •4e ,3 ta I. a* 20 4B 60 Be° .0 120 140 160 s e...conditioned profile after length and power normalization. 2 Neural-Based Feature Extraction 2.2 Contrast enhancement and adaptive Rather than directly... power of the signal comprised of HRR range profiles synthesized from the is normalized. This ensures that very weak or very strong MSTAR SAR imagery